AFMR Southern Regional Meeting Abstracts ======================================== ## **Cardiovascular Club** 11:00 AM Thursday, February 12, 2009 ### 1 PROTECTIVE ROLE OF CHRONIC ANGIOTENSIN CONVERTING ENZYME INHIBITOR (ACEI) THERAPY IN REDUCING PERI-PROCEDURAL MYOCARDIAL INFARCTION IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION D. Bansal1,2, S. Aleti1,2, R. Sukhija1,2, R. Muppidi1,2, J. Mehta1,2, R. Sachdeva1,2, * 1Central Arkansas Veterans Healthcare Administration, Little Rock, AR and 2University of Arkansas for Medical Sciences, Little Rock, AR* #### Purpose of Study Peri-procedural myocardial infarction (MI) is a frequent complication of Percutaneous Coronary Intervention (PCI). Studies have shown that Angiotensin Converting Enzyme Inhibitors (ACEI) may improve endothelial function and may reduce ischemia-reperfusion myocardial injury. The study objective was to verify whether chronic treatment with ACEI reduces the occurrence of peri-procedural MI in patients undergoing PCI. #### Methods Used Study cohort was formed by all patients who had PCI done during January 2003 to August 2004 at one institution. Data were obtained on a total of 481 interventions of which 230 were done on patients on chronic ACEI therapy #### Summary of Results ACEI-treated patients had a higher prevalence of hypertension and diabetes. The incidence of peri-procedural MI was lower (6% vs. 13%, *P* value 0.014) among patients on chronic ACEI therapy. Incidence of contrast induced nephropathy was similar. Predictors of periprocedural MI are as shown in Table 1. Multiple logistic regression model including age, risk factors, pre-procedural medications and procedural characteristics like type of stent, glycoprotein IIb/IIIa inhibitor use identified pre-procedural chronic ACEI therapy as the only independent negative predictor of peri-procedural MI (odds ratio = 0.32; 95% confidence intervals 0.15-0.72; *P* = 0.005). View this table: [Table1](/content/57/1/301/T1) Predictors of peri-procedural myocardial infarction #### Conclusions Chronic therapy with ACEI reduces the incidence of periprocedural MI among patients undergoing PCI. This beneficial effect was independent of clinical and angiographic characteristics and the use of other cardiovascular drugs including statins and beta-blockers. Table 1. Predictors of peri-procedural myocardial infarction ### 2 OVEREXPRESSION OF DOMINANT NEGATIVE TRANSFORMING GROWTH FACTOR (TGF)-β TYPE II RECEPTOR (DnTGFβRII) ATTENUATES PRESSURE OVERLOAD-INDUCED CARDIAC REMODELING AND DYSFUNCTION J.A. Lucas, A.P. Miller, Y. Zhang, P. Li, S. Oparil, Y. Chen *University of Alabama at Birmingham, Birmingham, AL*. #### Purpose of Study We have previously used a transgenic mouse model that expresses an inducible DnTGFβRII to demonstrate that blocking TGF-β signaling reduces pressure overload-induced interstitial collagen deposition in the heart. The current study utilized DnTGFβRII mice to test the hypothesis that collagen deposition in the pressure overloaded heart is required to maintain structure and prevent left ventricular (LV) dilation and dysfunction. #### Methods Used 8-10 wk old DnTGFβRII and nontransgenic control (NTG) mice were given 25 mM ZnSO4 in drinking water to induce the expression of DnTGFβRII gene 1 wk prior to transverse aortic constriction (TAC). 120 days after TAC or sham operation, LV mass, dimension and function were assessed by echocardiography. LV interstitial collagen content was assessed in picrosirius red stained sections by light microscopy. #### Summary of Results LV end diastolic and systolic diameters (LVEDD and LVESD) were significantly increased in Zinc treated DnTGFβRII mice after TAC, while ejection fraction (EF) and fractional shortening (FS) were significantly decreased in this group compared to the other five treatment groups (Table). The DnTGFβRII group receiving H2O only did not differ from NTG mice in any parameter. TAC induced collagen deposition was significantly attenuated in the TAC-DnTGFβRII + Zinc mice only. #### Conclusions These data support the hypothesis that intact endogenous TGF-β signaling is required to protect against LV dilation and dysfunction in the presence of pressure overload stress. View this table: [Table2](/content/57/1/301/T2) ### 3 VE-CADHERIN IS ESSENTIAL FOR NORMAL CARDIAC DEVELOPMENT BUT NOT VASCULAR SPROUTING IN ZEBRAFISH T. Brown1, I. Mitchell1, J. Amatruda2, F. Nwariaku1 * 1University of Texas Southwestern Medical Center, Dallas, TX and 2University of Texas Southwestern Medical Center, Dallas, TX*. #### Purpose of Study VE-Cadherin (VE-Cad) is a structural protein that has demonstrated significance in angiogenesis, although its precise role in vivo remains unclear. Our goal was to create a robust in vivo VE-Cad knockdown model using zebrafish, and to subsequently evaluate the development, function, and structure of the cardiovascular system in the absence of VE-Cad. #### Methods Used An antisense morpholino targeting the translational start site of VE-cad mRNA (VE-Cad MO) was synthesized, and 2 nL of 0.5 mM VE-cad MO or a standard control morpholino was injected into the yolk of single-cell stage embryos. After injection, embryos were observed to quantify cardiovascular phenotype. Measurements of circulation, pericardial edema, and cardiac folding were made. At 24 hour intervals, both heart rate and perfusion were measured. Number of erythrocytes passing through the two most distal patent arteries was counted to assess perfusion. To measure the endocardial/myocardial separation, injected fli1:GFP transgenic embryos were used (GFP + endocardium, GFP- myocardium). #### Summary of Results Knockdown of VE-Cad results in failure for circulation to initialize, pericardial edema, and absent cardiac folding, resulting in cardiovascular failure and embryonic mortality between 72-96 hpf. There was also a statistically significant increase in separation between the endocardial and myocardial elements in the VE-cad MO injected fish. Neither heart tube formation, primitive hematopoiesis, nor vascular sprouting are affected by VE-cad knockdown. #### Conclusions In conclusion, the knockdown of VE-Cad produces early circulatory arrest, pericardial edema, and cardiac looping failure in embryonic zebrafish without affecting vascular development. This robust, reproducible system has potential to yield insight into the complex signaling role of VE-Cadherin in early cardiac development. The zebrafish knockdown model allows manipulation of VE-Cad in the living organism with reproducible, easily identifiable effects. Its potential applications include in vivo analysis of VE-Cad signaling, endocardial/myocardial interaction, structure/function assays, and screening for agents which affect VE-Cad signaling. ### 4 ENDOGENOUS INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTECTS AGAINST APOPTOSIS & CARDIAC REMODELING AFTER ACUTE MYOCARDIAL INFARCTION A. Varma, F.N. Salloum, N.N. Hoke, B.W. Van Tassell, A. Abbate, G.W. Vetrovec *VCU Pauley Heart Center, Richmond, VA*. #### Purpose of Study Apoptosis & inflammation are two key pathological features of post-infarction remodeling. Interleukin-1 (IL-1) signaling is involved in both apoptosis & inflammation in response to ischemia. We hypothesized that during ischemia, IL-1 receptor antagonist (IL-1Ra), an endogenous IL-1 inhibitor, plays a protective role & therefore mice lacking the IL-1Ra gene (knock out - KO) would be more susceptible to apoptosis & adverse cardiac remodeling after acute myocardial infarction (AMI). #### Methods Used Seven KO mice & 8 age-matched wild-type (WT) mice underwent surgical ligation of the left coronary artery. All animals underwent transthoracic echocardiography before surgery & at day 7. Infarct size and cardiomyocyte apoptosis were measured using collagen staining & in situ detection of DNA fragmentation, respectively. #### Summary of Results Seven days after AMI, KO mice showed increased left ventricular end-diastolic diameter & end-systolic diameter with reduced fractional shortening vs WT mice [Figure]. An average of 5 aneurysmatic segments were seen in the KO mice vs 1 segment in the WT mouse (*P* = 0.010). KO mice also had a significantly larger area of scar (35 ± 2% vs 23 ± 2%, *P* = 0.009) & significantly greater cardiomyocyte apoptosis in the peri-infarct myocardium (9.5 ± 2.2% vs 1.9 ± 0.1%, *P* = 0.022) compared to WT mice. #### Conclusions Endogenous IL-1Ra protects cardiomyocytes from apoptosis, prevents adverse cardiac remodeling & aneurysm formation after AMI. The cardioprotective effect of endogenous IL-1Ra on apoptosis affirms a role for IL-1 signaling & the potential for IL-1 based treatment strategies to prevent heart failure after AMI. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F1.medium.gif) [Figure.](/content/57/1/301/F1) Figure.   ## **Adult Clinical Case Symposium** 1:00 PM Thursday, February 12, 2009 ### 5 HEPATIC SICKLE CRISIS WITH ACUTE HEPATIC FAILURE AND SEQUESTRATION B.W. Davis, E.B. Clyburn *Medical University of South Carolina, Charleston, SC*. #### Purpose of Study Sickle cell crises manifest as multiorgan involvement secondary to an amino acid substitution of valine for glutamic acid resulting in polymerization of deoxy hemoglobin and subsequent vaso-occlusion. Common presentations include bone infarction, acute chest syndrome, and cerebrovascular events; however, hepatic involvement occurs in approximately 10 percent of sickle cell crises and results in liver sequelae. Acute hepatic crises with hepatic failure can pose a diagnostic challenge as well as indicate for quick therapeutic intervention. We report a case of hepatic sickle crisis where early intervention resulted in a favorable outcome. #### Methods Used 33-year-old African American male with a history of sickle cell disease and sarcoidosis presented with chest pain radiating to the epigastrium and shortness of breath. Physical exam revealed him tachycardic, afebrile, and oxygen saturations at 92% on room air. Additionally, there was jaundiced skin, lung crackles, and epigastric distention with right upper quadrant tenderness. The liver edge was palpable 10 cm below the costal margin and extended to midline. Laboratory studies were WBC 15, hemoglobin 7.9, platelets 330, total bilirubin 35.2, AST 207, ALT 118, alkaline phosphatase 664, total protein 7.35, albumin 2.5, and PT/INR 18.6/1.5. Chest radiography was suggestive of lobar pneumonia and antibiotics were begun. Right upper quadrant ultrasound revealed no evidence of biliary ductal dilatation; however, the liver measured 19 cm in diameter. Supportive treatment and antibiotics continued until hospital day 3 when there was worsening mental status, respiratory distress, coagulopathy, rise in bilirubin, and a hemoglobin decrease. At this time, acute hepatic sickle crisis with hepatic failure and sequestration was diagnosed. Prompt exchange transfusion was performed and rapid improvement followed with transaminases at baseline. Our patient was discharged home in stable condition. #### Summary of Results While sickle cell hepatopathy is infrequent, acute hepatic crises possess devastating sequelae. Although diagnostic criteria still remain undefined, early intervention with exchange transfusion can reduce mortality. #### Conclusions In reporting this case, we illustrate the importance of early diagnostic recognition and exchange transfusion to avoid further devastating outcomes. ### 6 "I'M NOT DRINKING THE WATER": A CASE REPORT INVOLVING SEVERE HYPERNATREMIA, RHABDOMYOLOSIS AND ACUTE KIDNEY INJURY B.M. Statham, S. Kanikireddy, P.F. Bass *LSUHSC Shreveport, Shreveport, LA.* #### Case Report Introduction: Nephrogenic Diabetes Insipidis (DI) is a condition that interrupts patient's ability to concentrate their urine and consequently they live in constant danger of dehydration that can lead to impaired mental status or death. We report a case of a patient with congenital nephrogenic DI developing severe hypernatremia leading to rhabdomyolosis, hyperkalemia and acute kidney injury. Case Report: A 20 year-old incarcerated male presented with a complaint of lower extremity muscle cramps and generalized weakness for three days. The patient denied any recent trauma, exertion or exposure to extreme climate. He reported excessive thirst and urination since childhood, consistent with his diagnosis of DI that was ultimately confirmed by family. Other than clinical signs of severe dehydration, physical exam was normal, including a normal neurological exam. Initial laboratory data revealed serum sodium 202 mmol/L, potassium 2.4 mmol/L, Chloride >150 mmol/L, CO2 24 mmol/L, BUN 37 mg/dL, creatinine 1.7 mg/dL. The patient underwent aggressive volume replacement with normal saline, followed by large amounts of maintenance fluids, including 1/2 normal saline and D5 with bicarbonate. The patient was also started on amiloride and hydrochlorothiazide. After three days the patient's sodium decreased to 167 mmol/L; however, his creatinine phospokinase levels reached 500,000 U/L, with potassium 7.7 mmol/L, creatinine 3.5 mg/dL and hemodyalysis was initiated. Discussion: A dramatic alteration of body water homeostasis can be observed in individuals with diabetes insipidus. However, such severe hypernatremia in the absence of neurological deficits is unusual with only a few case reports with serum sodium >200. Diet modifications and medications can be employed to diminish the danger of dehydration and help control thirst, but when homeostasis cannot be maintained, patients are at risk for developing severe hypernatramia. The above patient had recently been incarcerated and had refused to drink the water provided, which lead to his disruption in homeostasis. Rhabdomyolysis and acute kidney injury are possible complications of severe hypernatremia, which were both evident in this case. ### 7 HYPERBARIC OXYGEN RELIEVES DIGITAL ISCHEMIA FROM ACCIDENTAL EPIPEN INJECTION P. Klemawesch, J. El-Dahr *Tulane University, New Orleans, LA.* #### Case Report PJ Klemawesch, J El-Dahr. Tulane University, New Orleans, LA. Rationale: Treatment for accidental digital auto-injection of epinephrine is not standardized and described treatments have varying efficacy. Methods: We describe the case of a 30 yo white male physician who accidentally autoinjected an EpiPen into his thumb during a code situation. The pt had severe ischemic symptoms and long-term complications including loss of function and surgical correction were anticipated by evaluating specialists. Warm water immersion and local phentolamine did not relieve symptoms of digital ischemia. The patient was treated with hyperbaric oxygen 2.4 atm, 90 min for 3 treatments. Results: Symptoms of ischemia, including pallor, pain, and slow capillary refill were alleviated entirely after hyperbaric treatment Conclusions: Hyperbaric oxygen is an effective alternative treatment for digital ischemia resulting from accidental EpiPen auto-injection. To our knowledge, this is the first reported case of hyperbaric oxygen successfully treating digital ischemia from epinephrine injection ### 8 WHEN GOOD IS BAD T.D. Alford, S. Kosseifi, E. Celso, C. Trabue, J. Moorman, R.D. Smalligan *East Tennessee State University, Johnson City, TN.* #### Case Report Introduction: Progressive multifocal leukoencephalopathy (PML) most commonly occurs in patients with HIV but can be seen in other immunodeficiency states. We report PML in the setting of a rare immunodeficiency caused by thymoma (Good's syndrome). Case: A 65yo woman presented with rapidly progressive dementia. She was well until 3 months prior when she developed increasing forgetfulness and confusion which progressed. She had not traveled outside of the USA, nor had any tick bites, nor any known exposure to HIV, herpes, syphilis, or TB. Meds: HCTZ, simvastatin, donepezil. She was married and denied alcohol, tobacco, or drug use. No family history of premature dementia, psychiatric, or immunologic disease. Physical exam: stuporous, afebrile, 125/68, O2 sats 94%, no thrush, lymphadenopathy, carotid bruits, or thyromegally; heart, lung, abdomen, extremity, and skin exams all normal. Neuro: strength 4/5, no tremors; DTRs 1+. Labs: Cr 0.9, Na 140, Ca 9.3, gluc 123, AST/ALT/AP normal, ESR 7, WBC 8.7, RPR non-reactive, ANA and HIV negative, TSH 2.0, B12 1080, IgA 15 (66-436), IgG 582 (791-1643), IgM <25 (43-279). LP: no WBCs or RBCs; neg for bacteria, fungi, and AFB; but PCR-positive for JC virus DNA. CT: 7 × 7 cm mass in the right anterior hemithorax. Biopsy of mass: thymoma without malignant features. Brain MRI: subcortical edema throughout felt to be consistent with PML. Discussion: Good's syndrome is an adult-onset immunodeficiency in the setting of thymoma characterized by hypogammaglobulinemia (IgA, IgG, and IgM) as was seen in our patient. She was also positive for JC virus, a polyomavirus with which 70-90% of all humans are infected. Typically this infection is associated only with a viral syndrome which resolves but in immunocompromised patients the virus can reactivate and replicate within oligodendrocytes causing lysis and rapid demyelination in the brain white matter. This process is termed progressive multifocal leukoencephalopathy and presents with dementia and/or ataxia. While PML is almost exclusively associated with HIV/AIDS, our patient was HIV negative. In our case it appears that Good's syndrome caused the immunodeficiency which permitted the JC virus to reactivate and cause this fatal case of PML. The authors could find no other case reports of Good's syndrome in association with PML. ### 9 DRUG-INDUCED LUPUS NEPHRITIS AFTER INFLIXIMAB TREATMENT FOR ULCERATIVE COLITIS S. Gates, R. Ravenell, D.L. Kamen *Medical University of SC, Charleston, SD.* #### Case Report We report a 34-year old female with a history of ulcerative colitis and primary sclerosing cholangitis who became anti-nuclear antibody (ANA) positive and developed lupus nephritis (LN) after receiving infliximab, a TNF-α inhibitor. The purpose of this report is to describe her presentation and present a review of the literature on TNF-α inhibitor-induced lupus nephritis. A literature search was conducted and these cases were compared and contrasted to our patients. Early 2008, the patient was found to be ANA negative during evaluation for a liver transplant. She subsequently received two infusions of infliximab for active ulcerative colitis. Three months following her last infusion, she presented to the ER with weakness and fever secondary to pneumonia and sepsis. She was found to have 1.4 g protein/day of proteinuria and active urinary sediment. Lab tests revealed positive serologies for ANA, dsDNA and histone ab and low complements. Kidney biopsy revealed class III LN and acute tubular necrosis. In the 7 case studies previously reported, all but one patient had their TNF-α inhibitor discontinued and they were subsequently treated with alternative immunosuppressants. The one patient that was continued on the TNF-α inhibitor eventually developed severe pulmonary disease and died. One patient required short-term hemodialysis. The remainder of the patients had resolution of their symptoms after the TNF-α agent was discontinued and treatment with the alternative immunosuppressive agent began. After our patient was diagnosed with drug-induced LN, she received solumedrol 1 g for 3 days followed by oral medrol 48 mg with clinical improvement of her symptoms. She was discharged home on prednisone 40 mg and scheduled to follow up in the Rheumatology clinic. Literature teaches us that drug-induced lupus does not involve the kidneys. Our case adds to the 7 published cases of TNF-α induced LN. In 6 of the 7 published cases, resolution of symptoms occurred after the TNF-α agent was discontinued. It was 4 months after our patient's last infliximab infusion when she was found to have LN. Continued follow-up is needed to confirm the clinical improvement of her lupus-like syndrome. ### 10 TREATMENT OF PROFOUND LACTIC ACIDOSIS IN A COCAINE INTOXICATED RESTRAINED PATIENT H.M. Alshayeb1,2, W. Chishti1, A. Showkat2, B.M. Wall1,2,3 * 1UT-Memphis, Memphis, TN; 2UT-Memphis, Memphis, TN and 3VAMC, Memphis, TN.*. #### Case Report Severe lactic acidosis which has been reported to occur in patients struggling against restraints, especially in association with the use of stimulant drugs such as cocaine, can lead to cardiac arrhythmias and cardiac arrest. Removing the stimulus for lactic acid production (excessive muscle activity) by aggressive sedation and ventilatory assistance coupled with fluid administration to improve tissue perfusion can be life-saving. A 24 year old male presented with agitated delirium and hypertensive urgency after cocaine abuse and required restraint in the prone position for self protection. Due to continued combativeness, the patient required sedation, muscular paralysis and mechanical ventilation. Vital signs before intubation were Bp 224/120 mmHg, HR 180 b/min. Physical examination was unremarkable. Laboratory studies revealed Serum creatinine 1.9 mg/dl and BUN 9 mg/dl. HCO3 - 7 mEq/l. Serum Na +, K +, Cl-, Ca + 2 and PO4-3 were normal. Plasma anion gap 29 mEq/l, plasma lactate 20 mmol/l, blood glucose 327 mg/dl, albumin 4.1 gm/dl, CPK 231 U/l, blood alcohol level 104 mg/dl, and serum osmolality 315 mosm/kg H20, and the corrected plasma osmolal gap 5 mosm/kg H20. Serum and urinary ketones were negative. ABG showed a pH 7.10, PaCO2 44 mmHg, HCO3 - 12 mEq/l, PaO2 327 mmHg (FIO2:100%). Salicylate and acetaminophen levels were undetectable. Urine drug screen was positive for cocaine. EKG showed sinus tachycardia (175 bpm). Abdominal CT examination was normal. Cardiac injury was ruled out with normal EKGs and negative troponins. After 3-hours of sedation, mechanical ventilation and 4 L normal saline administration, repeat laboratory studies showed plasma lactate level of 2.0 mmol/l, Cr 1.1 mg/dl, HCO3 - 23 mEq/l, anion gap 4 mEq/l and glucose 86 mg/dl. The patient was weaned from sedation and extubated with no complications. #### Conclusion Severe lactic acidosis is a recognized life threatening emergency occurring in patients with agitated delirium who are struggling against restraints, especially in association with stimulant drugs, such as cocaine. Early intervention including sedation, muscle paralysis, fluid administration, and mechanical ventilation can be life saving. ### 11 AN UNUSUAL CASE OF RESISTANT HYPOPHOSPHATEMIA WITH CHIARI MALFORMATION O.A. Iznaola, S.S. Prabhakar *Texas Tech University Health Sciences Center, Lubbock, TX.* #### Case Report Case summary We describe here a 39 year old white female with childhood rickets and persistent and refractory hypophosphatemia since her adolescence. Investigations including genetic analysis confirmed X-linked hypophosphatemia (XLH) The patient had multiple sequelae, including chronic pain, recurrent headache, and musculoskeletal malformations like short stature, bowed legs and spinal stenosis requiring spinal surgery. She was treated with oral phosphate supplements and calcitriol, which improved her biochemical parameters, as well as symptomatic treatment for chronic pain. In the last 5 years, the serum calcium ranged from 8.0-9.8 mg/dl, phosphorous 1.5-3.2 mg/dl, creatinine 0.5-0.7 mg/dl and iPTH 29-40 iu. Of interest is the fact that an investigation of recurrent headaches by MRI led recently to the diagnosis of Chiari malformation. Discussion XLH has an incidence of 1 in 20,000. These patients have abnormal phosphaturia leading to phosphorus depletion and musculoskeletal derangements in childhood (rickets) and adulthood (osteomalacia). Despite severe bone malformations and late diagnosis of the disease, our patient maintained normal renal function with no evidence of hyperparathyroidism and enjoyed a relatively good quality of life. The association of XLH with Chiari malformation is extremely rare (only 2 published reports so far). Recent investigations in the pathophysiology of this disease suggest that PHEX gene may cause an aberrant PHEX protein. Its substrate, while not yet identified, has been named phosphatonin. Phosphatonin FGF23 may be the one of the substrates and has been reported to be elevated in XLH patients. FGF-23 may reduce Na-dependent Pi transport in the kidney and induces phosphaturia. Studies suggest that the combination of 1,25(OH), D, and 24,25(0H), D, may be superior to either agent alone in the restoration of normal mineralization in XLH. X-linked hypophosphatemia is a relatively rare disorder with severe musculoskeletal malformations. The association with recurrent headaches warrants a screening for Chiari malformation, in this population since the diagnosis may often be missed. Also, the recent discovery of PHEX gene and FGF-23 as a possible factor in renal phosphate wasting opens the doors for potential new treatment options. ### 12 ISOLATED PITUITARY METASTASIS FROM SMALL CELL LUNG CANCER A. Aravapalli, E. O'Bryan *MUSC, Charleston, SC.*. #### Case Report 69-year-old Caucasian male with 50 pack year smoking history presented initially with two month history of hemoptysis and twenty pound weight loss. CT of thorax revealed 2.6 × 2.5 cm right hilar mass with right hilar lymphadenopathy suspicious for malignancy. Patient was scheduled for PET scan and transbronchial biopsy, however, prior to biopsy, the patient presented to the ER with right temporal headache. Physical exam findings upon admission included blurry vision and decreased pin-prick sensation in right trigeminal nerve. Head CT and subsequent MRI showed 1.1 × 1.3 cm high density suprasellar mass extending inferiorly into the sphenoid sinus and superiorly into the suprasellar region, compressing the left undersurface of the optic chiasm. There were no definite metastatic lesions identified on MRI. Of interest, patient had a Brain MRI six months prior for sinus problems that was within normal limits. Whole body PET scan corresponded with prior CT of thorax showing hypermetabolic right hilar mass without other areas of hypermetabolic activity. Transbronchial biopsy was expedited, revealing small cell lung cancer. On formal visual fields testing, bitemporal hemianopsia consistent with chiasmal compression was found. Due to intense headache and optic nerve compression, Neurosurgery performed a trans-sphenoidal biopsy with partial debulking of the pituitary mass with differential diagnosis of metastasis from lung versus separate primary tumor. Histology revealed small cell cancer of the pituitary. The patient was referred to Oncology with a diagnosis of extensive stage small cell lung cancer, and at time of this report, was scheduled to undergo cranial irradiation dose of 30 Gray in 10 fractions and subsequent systemic chemotherapy with carboplatin and etoposide. That only 1 to 2% of pituitary tumors are due to metastases lends significance to this case. When metastases do occur, they most commonly arise from the two most common malignant cancers: lung and breast cancer. Unlike this patient, the majority of pituitary metastases are asymptomatic. Only 7% show symptoms that can include diabetes insipidus, headache, and visual field deficits. Although surgical treatment of pituitary mass can improve a patient's quality of life, there is no recorded overall improvement in survival, with mean survival rates 6 to 22 months after diagnosis. ### 13 POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME IN A PATIENT WITH LUPUS NEPHRITIS F.S. Pasha, A. Bond, V. Majithia, R. McMurray *University of Mississippi, Jackson, MS.* #### Case Report Introduction: Posterior reversible encephalopathy syndrome (PRES), may present with a variety of neurological manifestations: headache, seizure, altered mental status, cortical blindness, focal neurological deficits, or vomiting in association with transient changes in brain MRI imaging of cerebral edema primarily involving the parietal and occipital lobes. PRES most often occurs in the clinical setting of hypertension, eclampsia, renal failure, or immunosuppression. Case: A 17-year-old African-American girl with an 8 year history of SLE who presented with new onset seizures, altered mental status, hypertension, vomiting and blood pressure of 164/122. Diagnosed in 2005 with WHO Class IV Lupus Nephritis, the patient had nephrotic range proteinuria for the past year. She received a 6-month course of cyclophosphamide one-year ago but was switched to mycophenolate mofetil, due to cyclophosphamide intolerance. The patient also received one treatment course with rituximab four months prior to admission. MRI on admission showed hyper-intense T2/FLAIR lesions of the cerebellar hemispheres bilaterally as well as abnormalities of the bilateral cerebral hemispheres localized to the occipital lobes. The patient was treated with intravenous solumedrol for active lupus nephritis and thrombocytopenia. Blood pressure was controlled by intravenous anti-hypertensive, which resolved the vomiting and altered mental status. Follow-up MRI four days later showed significant resolution of the cerebellar lesions although persistence of the occipital lesions. There was marked improvement of all lesions on the MRI done one month later. Discussion and Conclusion: PRES is not unique to lupus but should be considered in an SLE patient presenting with neurological symptoms. PRES needs to be distinguished from lupus cerebritis, infection related to immunosuppressive therapy and thrombotic events as the treatment for each is obviously very different. Currently, the pathophysiology of PRES is unclear and controversial. Further research is needed to determine the mechanism, but regardless of the etiology, prompt control of blood pressure leads to resolution of symptoms and MRI changes. ### 14 RETINOIC ACID SYNDROME, A MEDICAL/ONCOLOGIC EMERGENCY L. Mirza1, N. Balouch2 * 1Uinversity of Oklahoma, Oklahoma City, OK and 2Hillcrest hospital, Tulsa, OK.* #### Purpose of Study Case report for the prompt recognition and treatment of a fatal complication. #### Methods Used Case report #### Summary of Results We report a case of retinoic acid syndrome (RAS), an oncologic emergency that can arise as a result of treatment of acute myelocytic leukemia (AML) with all-trans retinoic acid (ATRA). RAS is a life threatening condition that requires prompt diagnosis and treatment in order to avoid significant morbidity and mortality. It is crucial for a general internist to be familiar with the clinical characteristics and appropriate treatment of this uncommonly seen disorder in a medical ward. A 36 year old man developed fatigue and cough followed by a fever. He was treated with levofloxacin for pneumonia. Blood work in the emergency department revealed acute myelocytic leukemia. Patient was started on retinoic acid and idarubicin for the treatment of AML. He developed fevers again and complained of non pleuritic chest pain one week later. Computed tomography (CT) chest showed interval increase in the extent of the bilateral diffuse and patchy infiltrates. Two-dimensional echocardiogram showed small pericardial effusion. Electrocardiogram (EKG) was consistent with acute pericarditis. He had no previous history of cardiac disease. Retinoic acid syndrome (RAS) was diagnosed due to the aggregation of symptoms such as fever, pulmonary infiltrates, pericardial effusion and respiratory distress. Patients should have three of the seven signs fever, respiratory distress, pulmonary infiltrates, weight gain, hypotension, renal failure pleural or pericardial effusions for the diagnosis of RAS according to the literature. Retinoic acid treatment was discontinued. High dose intravenous dexamethasone therapy was initiated with significant improvement in this patient's signs and symptoms proven with repeat CT scan of the chest within a few days. Randomized clinical trials are not available for management guidelines but case series have shown benefit with high dose dexamethasone treatment. It is also questionable whether discontinuation of ATRA after the development of symptoms has any benefits. #### Conclusions Nevertheless, it is important for a general practitioner to learn about this potentially fatal condition. ### 15 LOIN PAIN-HEMATURIA SYNDROME - A DIAGNOSTIC MYSTERY S. Kanikireddy, P. Bass *LSUHSC, Shreveport, LA.* #### Case Report INTRODUCTION: The loin pain-hematuria syndrome (LPHS) is characterized by repeated episodes of severe flank pain associated with hematuria without the evidence of major causes for flank pain. LPHS tends to be more common in women and young individuals. Though the disease is associated with IgA nephropathy and nephrolithiasis in some instances, workup remains negative in the majority of cases. Urinalysis is an important diagnostic tool as it may show RBCs. Most LPHS patients end up undergoing kidney biopsy which may demonstrate red blood cells in glomeruli and/or glomerular thinning which indicates glomerular bleeding as the source of hematuria and aid in the diagnosis. CASE PRESENTATION: We present the case of a 31 year old Hispanic male presenting with severe right sided flank pain for more than one year. Pain appeared to be out of proportion to the clinical findings. The patient reported 3 to 4 episodes of gross hematuria in the past one year. Common causes of hematuria were excluded. Before this presentation, the patient had been worked up at multiple facilities and the diagnosis of LPHS was suspected. Records from outside hospital suggested that patient may have drug seeking behavior. Physical exam on presentation to our facility was unremarkable except for bilateral flank tenderness. Urinalysis showed large blood with more than 75 RBCs per high power field with moderate hyaline casts. CT-scan with stone protocol was negative. Kidney biopsy was done which showed thinning of glomerular membranes and effacement of foot processes. DISCUSSION: Loin pain-hematuria syndrome is a challenging disease both in terms of diagnosis and management. Patients occasionally are labeled as drug seekers and referred to psychiatry as the work up remains negative. Besides pain control, prevention of exacerbations seems to be the main therapeutic approach. There are reports of ACE inhibitors providing some success in reduction of frequency and severity of exacerbations. In patients with history suggestive of nephrolithiasis, reducing the risks seems to decrease the frequency of attacks. Sodium thiosulfate infusion to dissolve calcium crystals, which may trigger pain, was tried with some success. Invasive procedures like renal denervation and renal autotransplantation appears to be promising but carry the risks of surgery and recurrence of symptoms is not uncommon. ## **Pediatric Clinical Case Symposium** 1:00 PM Thursday, February 12, 2009 ### 16 ACQUIRED COMPLETE HEART BLOCK SECONDARY TO TRAUMATIC SEPTAL TEAR W. Davis, K. Hewett, W. Lutin *Medical College of Georgia, Augusta, GA.* #### Purpose of Study To investigate a case of traumatic ventricular tear #### Methods Used Case study #### Summary of Results A previously healthy 6 year-old male was seen at a referring hospital following a motor vehicle accident. The child was unrestrained in the back seat. He lost consciousness immediately, but was awake and alert on addmission. On arrival, he was pale, bradycardic, hypotensive and had multiple abrasions and lacerations. Blood pressure was 79/32, heart rate was 49 bpm with faint radial pulses. Cardiac exam was unremarkable with a quiet precordium, normal S1 and S2 and no murmurs or clicks. An electrocardiogram demonstrated complete (third-degree) AV block, left bundle branch block, and an episode of non-sustained ventricular tachycardia. A temporary transvenous pacing catheter was inserted. An echocardiogram was performed at the bedside which showed a ventricular septal tear with no evidence of left to right shunting and basilar inferior wall dyskinesis with overall good left ventricular function. Intravenous Milrinone gtt at 1 mcg/kg/min was begun due to the patient's increased susceptibility to arrhythmias, particularly ventricular tachycardia. Due to risk of ventricular septal rupture, the child was transferred to another hospital where a pediatric cardiothoracic surgeon was available. There the patient's other injuries were further stabilized and cardiac function was closely observed. No further treatment was required for his ventricular septal tear or AV block. 24 days after the accident, the child was seen for cardiac follow-up where EKG continued to demonstrate left bundle branch block, however, he was now in first-degree heart block instead of third-degree. Echocardiogram remained unchanged. #### Conclusions Cardiac injuries are a common result of blunt chest trauma acquired during high-speed motor vehicle accidents. In rare cases, ventricular septal tear may occur. Echocardiography is the best diagnostic modality for identifying this abnormality. Close monitoring and follow-up is required as hypotension, arrhythmia, and septal rupture are possible complications ### 17 AN UNUSUAL PRESENTATION OF WEGENER'S GRANULOMATOSIS IN A CHILD L. Toups1, W. Wells1, B. Swartz2, * 1LSUHSC Children's Hospital, Shreveport, LA and 2LSUHSC, Shreveport, LA.* #### Case Report 11 year old African American female presented to outside hospital with chief complaint of chest pain and shortness of breath for 1 month prior to presentation. She was initially treated for asthma with no improvement. She presented again with increased symptoms and was transferred to our instituition. Pertinent positives in review of systems included cough, abdominal pain, malaise, poor appetite, nausea, vomiting, recent contact with someone on antituberculosis medications, and a 27 pound weight loss in 2 months. Pertinent negatives included no hemoptysis or in-home smokers. Chest xray showed large mass in right perihilar area. Subsequently, CT of lung revealed large mass below the carina partially obstructing the right mainstem bronchus and a cavitary mass in the right lower lobe suspicious for neoplasm. Inconclusive laboratory data showed elevated ESR, negative ANCA studies, PPD, and histoplasmosis titers. Resection of the lesion was performed. Patholgy revealed vasculitis and granulomatous inflammation with necrosis consistent with Wegener's Granulomatosis. Patient is being treated with the combination of methotrexate and corticosteroids and maintains close follow up with primary care physician and rheumatology. View this table: [Table3](/content/57/1/301/T3) ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F2.medium.gif) [Figure.](/content/57/1/301/F2) Figure.   ### 18 MARATHON QUEST FOR CAUSE OF SPRINTER'S DYSAUTONOMIA R. Philip, R.D. Smalligan *etsu, Johnson City, TN.* #### Case Report A 16 yo male track athlete presented with syncope, bradycardia, hypotension and hypothermia. He presented with 1 month of progressive lower limb weakness, salt craving, cold intolerance, constipation and a 30 pound weight loss. No trauma, viral illness or drugs. PMH/FH neg. PE: T94, P25, BP 96/71, RR16 Sao2 100(RA), BMI:18.2, lungs:clear; heart:bradycardia without murmurs; abdomen:normal; muscle tone/joints:normal, nonfocal neurologic exam except patellar and ankle reflexes 1 + and 3/5 strength in lower extremities. He required an isoprotrenolol drip to keep his heart rate over 40/minute during extensive testing by cardiology, endocrinology, rheumatology, oncology and neurology consultants. Labs: CBC, CMP, TSH, ACTH stimulation test and lumbar puncture were all normal. Viral titers, drug screen, rheumatology and endocrine tests - negative except testosterone 124. EKG: sinus bradycardia; Echocardiogram and MRI: unremarkable. Autonomic testing showed an abnormal valsalva manuever/failure of sympathetic nervous system. He went home on midodrine/caffeine but continued with significant symptoms. 2 weeks later his anti-acetylcholine-receptor(AchR) antibody returned high and he was given a trial of IVIG. PET/CT scan were negative for tumor. DISCUSSION: This case immediately raised suspicion of severe hypothyroidism or adrenal crisis as well as Guillain-Barre but these were quickly ruled out. Only weeks of extensive consultation and testing revealed the diagnosis: autoimmune autonomic neuropathy. This is an extremely rare disorder affecting the sympathetic and parasympathetic systems with manifestations ranging from abnormal GI motility and sexual dysfunction to life-threatening disturbances in heart rate and blood pressure as seen in our patient. The antibody mediated attack directed against the acetylcholine receptors of the autonomic ganglia is often triggered by an occult neoplasm that expresses the autoantigen but no obvious cause is found in more than a third of patients. Immunomodulatory therapy may ameliorate the severity of the disease but is not curative. This case illustrates the importance of the relentless pursuit of an elusive diagnosis through collaboration with the patient, fellow pediatricians and subspecialists. ### 19 EXERCISE STRESS TESTING IN PEDIATRIC PATIENTS WITH A STRUCTURALLY NORMAL HEART AND T WAVE INVERSION ON ELECTROCARDIOGRAM C. Snyder *Ochsner, New Orleans, LA.* #### Purpose of Study The purpose of this study is to evaluate the response of their T waves to the stress of exercise. #### Methods Used Inclusion criteria included a structurally normal heart and age less than or equal to 18. Data recorded included baseline ECG characteristics, demographics, peak heart rates and METS achieved, and heart rates at which T waves "normalized" during EST. All were exercised using Modified Bruce Protocol with continuous monitoring of their ECG's. Simple statistical analysis was utilized. #### Summary of Results We identified 13 patients with structurally normal hearts that were referred due to T wave inversion on a resting ECG (8 males and 5 females). Of race were Caucasian (6), African American (6), and Hispanic (1). Ages ranged from 8 to 18 with a mean of 14 and a median of 15.5. Eleven of thirteen (85%) of patients experienced complete T wave reversion with two of thirteen (15%) experienced partial (3/6 limb leads) reversion during EST. Mean peak heart rate was 192 beats per minute (bpm) (range 169-214) and mean maximum METS achieved was 13.2 (range 9-18.5). The average heart rate at which T wave reversion was met was 152 bpm (range 113-187) and a median of 153. The mean METS that T waves were reverted was achieved at 5.2 (range 1.0-12.3) and a median of 4.5. #### Conclusions Exercise Stress Testing pediatric patients with functionally and structurally normal hearts with T wave inversion on resting ECG resulted in complete or partial (100%) reversion of their T waves. This phenomenon occurs at an average heart rate of 152 bpm. It occurs in all sexes and ethnicities encountered. A large multi-centered study would remedy to improve the power of this study. View this table: [Table4](/content/57/1/301/T4) Results ### 20 SUCCESSFUL TREATMENT OF INTRACTABLE GASTROINTESTINAL BLEEDING IN HENOCH-SCHÖNLEIN PURPURA WITH RITUXIMAB: FIRST REPORTED CASE S.S. Wright, J. Nogueira, K. Thame, P. Atkinson, R.Q. Cron, S. Saeed *University of Alabama at Birmingham, Birmingham, AL.* #### Case Report The most common systemic vasculitis in children, Henoch-Schönlein purpura (HSP) is a small vessel vasculitis mediated by IgA-dominant immune complex deposits. It commonly affects the skin, gastrointestinal tract, joints, and kidneys. Gastrointestinal bleeding occurs in about half of children with HSP and is usually self-limited. We report a case of severe HSP in which the patient had persistent small bowel hemorrhage, requiring multiple blood transfusions, despite treatment with high dose steroids and cyclophosphamide. His intestinal bleeding resolved only after treatment with rituximab. A previously healthy 17 year old male presented with abdominal pain and bloody stools. He developed a purpuric rash and joint pain 7 days later. Protein and blood were found in his urine. The diagnosis of HSP was made, and he initially improved with symptomatic care. He was admitted to the hospital 4 more times over the next 2 months for severe intestinal bleeds requiring multiple transfusions. Renal biopsy showed proliferative glomerulonephritis with IgA deposits in the mesangium. Endoscopy revealed vasculitic lesions in the stomach. Multiple areas of small bowel mucosal bleeding were noted on video capsule endoscopy. These were not amenable to either endoscopic or surgical intervention. He received high dose intravenous methylprednisolone multiple times and then cyclophosphamide along with the high dose steroids; however, severe intestinal bleeding recurred upon each attempted steroid taper. One month after initiation of rituximab (1g IV twice, 2 weeks apart), our patient's previously refractory intestinal bleeding resolved. Mucosal healing was documented on repeat video capsule endoscopy. He is maintained in remission 4 months later on mycophenolate mofetil. A monoclonal anti-CD20 antibody, rituximab is approved to treat refractory rheumatoid arthritis and non-Hodgkin's lymphoma and is used off-label in the treatment of other rheumatologic diseases. Rituximab has not previously been documented as a successful treatment for GI complications of HSP. This case demonstrates that rituximab can be effective for severe complications of HSP such as gastrointestinal hemorrhage refractory to conventional treatment. ### 21 HYPOTONIA AND AN APPARENT LIFE THREATENING EVENT IN AN INFANT WITH ACHONDROPLASIA S.E. Joiner1, J. Picasso2, L. Crews2 * 1University of South Alabama, Mobile, AL and 2University of South Alabama, Mobile, AL.* #### Case Report Introduction: Achondroplasia is a genetic disorder with a mutation in the FGFR3 receptor which causes abnormal cartilage formation and is the most common skeletal dysplasia. Numerous associations have been noted including spinal stenosis. Case Presentation: A 7 week old male with a history of achondroplasia confirmed by genetic testing presented with fussiness, significant hypotonia, and increasing frequency of apparent life threatening events (ALTE) episodes. He was tolerating oral feeds well. The pertinent physical findings included typical features of macrocephaly, midfacial hypoplasia, a trident sign, and rhizomelia. Additionally, he had notable hypotonia in the upper extremities, absent Moro and grasp reflexes, and an impressive head lag associated with increased fussiness with examination. An MRI of the spine was performed immediately upon hospital admission and revealed bony stenosis at the craniocervical junction with abnormal cord signal likely secondary to edema. The patient's hypotonia and irritability resolved soon after surgical decompression of the craniocervical region was performed. Discussion: Spinal stenosis occurs in approximately half of all patients with achondroplasia with lumbar stenosis being most common and usually presenting in adulthood as parasthesias and claudication. Cervical stenosis, however, is uncommon occurring in only 3-7% of patients. This case illustrates the need to suspect cervical stenosis in patients with achondroplasia who present with irritability, hypotonia or ALTEs. This clinical scenario should prompt the need for immediate neurosurgical evaluation. ### 22 IDIOPATHIC HYPERCALCEMIA OF INFANCY AS A CAUSE OF FAILURE TO THRIVE M. Cuevas *USA Children's and Women's Hospital, Mobile, AL*. #### Case Report Hypercalcemia is not a common pediatric problem. Although believed to be less common in children versus adults, the actual incidence is unknown. 50 odd cases reported in USA during the past 14 years. 8 m/o WM who was admitted for FFT and noted to have hypercalcelmia. (Ca 15.6) PMHx significant for: At 5 m/o; 5-10 episodes of diarrhea/day. GI, Dx w/ milk protein allergy and reflux. Pt started on Prevacid, Zantac, and Neocate. Since 5 m/o, the weight had been below 5th percentile for age. At 7 m/o presented with anorexia, drank 10-12 oz/day of formula. Immediate fluid therapy was initiated. Endocrinology involved, steroids used. Rest of evaluation showed normal thyroid function, parathyroid, Vit D 25-OH and 1-25, PTHrP; iCa, renal US and skeletal survey. Idiopathic infantile hypercalcemia is a poorly understood disorder manifested by failure to thrive and hypercalcemia during the 1st year of life, followed by spontaneous remission. It can be classified roughly into two forms. Mild form: Hypercalcemia is the principal disturbance. Characteristically, there is FTT, usually of sudden onset between 3 and 7 m/o. While the sequeale of hypercalcemia is normally completely reversible with therapy, and probably even without therapy, a few patients have died during the acute hypercalcemic phase. Severe form: Infants with severe form have hypercalcemia and FFT of a degree similar to or greater than in the mild cases. In addition, several other more serious features occur. Recent publications have pointed out that, the severe form of infantile hypercalcemia frequently has its inception in utero. On our case, we can conclude that this patient had the mild form of idiophatic hypercalcemia of infancy. At hospital discharge, the patient had mild hypercalcemia Six months later, normocalcemia was obtained. Treatment consists of marked restriction of calcium intake, temporary elimination of both vitamin D and sunlight, and occasionally, administration of cortisone. Long-term prognosis is excellent. View this table: [Table5](/content/57/1/301/T5) 15 days prior: View this table: [Table6](/content/57/1/301/T6) At admission: ### 23 A CASE OF LETHAL PULMONARY HYPOPLASIA DUE TO MATERNAL ACE INHIBITOR USE S. Singh1, H.G. Ginsberg2, T.W. Young2 * 1Tulane University, New Orleans, LA and 2Ochsner Medical Center, New Orleans, LA.* #### Case Report The use of angiotensin converting enzyme (ACE) inhibitors in children and young adults has increased over the past decade. Second and third trimester ACE inhibitor use to significant fetopathy is well established. We present the case of an estimated 34 week gestation newborn female born to a 32 year old mother who had no prenatal care. Despite aggressive management of respiratory failure, pulmonary hypertension, and anuria, severe hypoxemia progressed. The mother provided a history of chronic hypertension which had been treated with a combination of medications including the ACE inhibitor benezepril. An echocardiogram revealed right to left flow through the ductus arteriosus and diastolic reversal of blood flow in the aortic arch. A chest X-ray suggested pulmonary hypoplasia. The baby expired at 22 hours of age. This case demonstrates the potential deleterious effects of maternal ACE inhibitor use during pregnancy and the importance of patient education. The reversal of blood flow in the aortic arch was an unusual finding. Flow reversal in the arch has been associated with poor prognosis in newborns with pulmonary hypertension and is explained in this patient by severe pulmonary hypoplasia. ### 24 COMA IN A 20-MONTH OLD CHILD FROM AN INGESTION OF A TOY CONTAINING 1,4-BUTANEDIOL, A PRECURSOR OF γ-HYDROXYBUTYRATE M.W. Jaeger, L. Ortmann, L. James, S. Schexnayder *University of Arkansas for Medical Sciences, Little Rock, AR.* #### Case Report 1,4-butanediol (1,4-BD) is an industrial solvent as well as a substance of abuse as it is metabolized to γ-hydroxybutyrate (GHB). We report a case of coma in a 20-month old boy from an ingestion of Aqua Dots, a toy containing 1,4-BD. He was found by his mother at home staggering "as if he was drunk". He proceeded to vomit colored beads found in his sister's Aqua Dots craft set. Upon presentation to the ED he was awake and crying, but quickly became somnolent and responsive only to painful stimuli. He had no respiratory distress or depression. The remainder of his physical exam was normal. His vital signs and oxygen saturation were normal. Initial lab values including a CBC, ABG and metabolic panel were also normal as was his CXR. He was transferred to the regional children's hospital and admitted to the pediatric intensive care unit where his GCS was 8. The remainder of his physical exam, vitals and sats remained normal. One dose of naloxone was given with no change in his mental status. The toxicology service was consulted. All labs including bedside glucose, basic metabolic panel, serum osmolality, urine screen for common drugs of abuse, acetaminophen and tricyclic antidepressant levels, RBC and plasma cholinesterase levels were normal as was his head CT. Initial investigations regarding the toxicity of Aqua Dots via the internet, poison control center, and product label revealed no published information. His GCS remained 8 until 5 hours into the course of his illness when the patient suddenly awakened and began speaking and playing with his family. His mental status remained normal and he was discharged home 23 hours after the ingestion with no further symptoms. After discharge from the hospital the patient's parents obtained a list of ingredients for Aqua Dots from the manufacturer. This list was reviewed by our toxicolgy service and included 1,4-BD, a known precursor to GHB. The family contacted the media and consumer safety advocates which sparked national media coverage and an immediate toy recall by the Consumer Product Safety Commission (CPSC). This case proved the need for tighter regulation and safety testing. The CPSC has since helped pass legislation in August 2008 to improve toy safety. ### 25 ABDOMINAL PAIN AS THE PRESENTING SYMPTOM FOR DISKITIS E. Grezaffi, L. Crews *University of South Alabama, Mobile, AL.* #### Case Report Introduction: Diskitis, inflammation or infection of the intervertebral disc space or veretebral endplate, is an uncommon condition in the pediatric population. This condition has varied clinical presentations with the most common as back pain and refusal to walk. Abdominal pain or pelvic pain is an unusual presentation for this condition particularly among toddlers. Case report: We report a previously healthy 3-year old African American female who presented with a two week history of intermittent abdominal pain. Suspicion for intussusception by the primary care physician prompted an admission for observation. Laboratory work-up which included a complete blood count, comprehensive metabolic panel, and urinalysis were normal. Blood and urine cultures were negative. The only abnormal laboratory finding was an elevated erythrocyte sedimentation rate at 56 mm/hr. An abdominal radiograph was unremarkable for obstruction or other abnormality. Although this patient was toilet trained prior, fecal and urinary incontinence were noted within 24 hours of hospitalization. Subsequently, the patient demonstrated difficulty ambulating with the recurrence of lower abdominal pain and unilateral tip-toeing on the left to alleviate the pain. The patient remained afebrile, and there were not other abnormal clinical findings. A MRI of the spine was performed and findings were consistent with diskitis at the level of L3/L4 with an associated epidural abscess. She completed prolonged intravenous antibiotics with complete resolution of symptoms and radiologic findings. Discussion: This case illustrates the need to include diskitis as a possible diagnosis in toddlers with abdominal pain and sudden onset of incontinence. ### 26 AN INFANT WITH FIRST-TIME SEIZURE N. Frascogna *University of Alabama at Birmingham, Birmingham, AL.* #### Case Report 10 week old FT baby girl was transferred from an OSH ED with a first-time seizure. The baby was in her usual health when mom dropped her off at the father's home earlier that day. She picked her up 4 hours later and noticed she felt hot to touch and was sweating, then began to shake and her eyes rolled back in her head. She was taken to an OSH where she was noted to have bilateral upper extremity shaking and R eye deviation. She was given 2 doses of Lorazepam with no cessation of seizure activity, then a loading dose of Fosphenytoin which stopped the seizure. She was noted to be febrile to 102. Blood and urine cultures were sent, an IO was placed secondary to inability to place an IV, and doses of Vancomycin and Ampicillin given. PE on arrival in our ED: T 100.9 P 175 R 65 BP 101/60 Sat 98% RA. In general she was awake, well nourished infant, AFSF, no scalp hematoma or markings, TM clear, no nasal discharge, pink MMM with clear OP, pupils 8mm and equal and sluggishly reactive, no eye deviation, heart tachycardic with RR, no murmur, strong distal pulses, lungs CTAB no inc WOB, ab soft, NTND, IO in R proximal tibia, no extremity deformities/tenderness/abnormal movements, skin diaphoretic with no rash or markings, awake but did not fix/follow, respond to voice, or cry appropriately with painful stimuli. Noncontrast head CT showed no fracture or intracranial hemorrhage. Labs showed CBC:WBC 14.0 Hb 9.4 Hct 27.0 Plt 474 43S/52L/0B; Lytes: Na 146 K 5.1 Cl 116 HCO3 19 BUN 8 Cr 0.3 Glu71 Ca 9.9; LFT: TP 6.0 Alb 3.9 ALT 31 AST 67 AP 276 TB 0.3; UA: SG >1030 1+ ketones 1-3 WBC 2-3 RBC few bacteria; CSF: Prot 41 Glu 50 WBC 0 RBC 0 GS neg; Blood, urine, CSF cultures, HSV PCR pending; Urine tox screen: positive for benzodiazepines, amphetamine, methamphetamine. This infant presented with a classic sympathomimetic toxidrome, though it would have been easy to overlook based on her age. This case illustrates the importance of keeping ingestions in the differential in all age groups. The baby was admitted for observation and antimicrobials until cultures returned negative. Toxicology and social work were consulted. The baby's father's girlfriend admitted to giving the child crystal meth in an attempt to harm her. She was arrested. The baby remained seizure-free and was discharged home with mom. ## **Case Reports in Cardiovascular Medicine** 1:00 PM Thursday, February 12, 2009 ### 27 A CASE OF CARDIAC DEVICE RELATED ENDOCARDITIS AND PERSISTENT SEPTIC ATRIAL THROMBUS J.F. Rodriguez, M. Celebi, R.D. Yount *LSU, New orleans, LA*. #### Case Report About 0.6 to 3.2% of patients with a cardiac device develop severe infection and endocarditis which carries a mortality rate close to 30%. It is generally accepted that IV antibiotic therapy and system removal have better outcomes than antibiotic treatment alone. Depite this, some cases have persistent thrombus or vegetation after device explantation. There are no well defined management criteria for these cases. We present a case of a 46 year old male with history of nonischemic cardiomyopathy who had implantation of a biventricular pacing defibrillator. Two years later the patient was found to have LV lead dislodgement and subsequently underwent unsuccessful revision of the lead. One month after the attempted revision an epicardial lead was placed. Eight months later he presented with fever and constitutional symptoms. Blood cultures were positive for coagulase-negative Staphylococcus. Echocardiography demonstrated a 1.9 cm mobile mass near the endocardial leads as they entered the right atrium. The endocardial leads and generator were explanted. The patient received six weeks of intravenous Vancomycin. Several weeks after completion of antibiotic therapy blood cultures were positive again. A new Echocardiogram revealed a mobile thrombus at the SVC/RA junction. Subsequently Catheter directed thrombolysis was performed by infusion of Alteplase. Echocardiography performed immediately after the procedure and 1 month later revealed no vegetation. A new course of intravenous antibiotic was given. Repeated blood cultures were negative. After 3 months patient underwent successful implantation of a new biventricular defibrillation system. Based on our case and literature review we suggest that local thrombolysis is a good alternative to surgical removal of persistent septic thrombi in cardiac device infection. The incidence of septic pulmonary emboli after thrombolysis is reported to be low in the few cases and studies found in our literature search. ### 28 SYSTOLIC DYSFUNCTION IN THE POST-LIVER TRANSPLANT PATIENT R.R. Bayer, K.C. Hilty, J. Peura *The Medical University of South Carolina, Charleston, SC.* #### Case Report A 68 year old white male with a history of cryptogenic cirrhosis was admitted for orthotopic liver transplantation (OLT). A dobutamine stress echocardgiogram obtained pre-operatively for cardiac risk stratification demonstrated normal systolic function with an ejection fraction (EF) of 60% without wall motion abnormalities. Stress images did not demonstrate focal wall motion abnormalities and EKGs also failed to demonstrate findings concerning for ischemia. He subsequently underwent successful OLT. On post operative day four he developed shortness of breath, lower extremity edema, and orthopnea. Cardiac bio-markers, EKG, and repeat transthoracic echocardiogram (TTE) were obtained. Cardiac enzymes returned normal and EKG was unchanged from pre-operative assessment. TTE demonstrated a depressed EF at 30% with global hypokinesis, but no focal wall motion abnormalities. His heart failure was treated medically with Furosemide, Metoprolol and Lisinopril with improvement in his symptoms over the next two days. He was discharged on the same medical regimen. Patients with advanced cirrhosis and end stage liver disease possess a hyperdynamic circulatory state. This hyperdynamic state is the result of an increased resting cardiac output and peripheral vasodilitation. The peripheral vasodilatation exists despite elevated levels of noradrenaline, angiotensin II, and other vasoactive peptides. This suggests that cirrhotics have an impaired response to serum vasopressors. Infusion of Endothelin-1 illicited a vasodilatory response in cirrhotics as opposed to controls where the expected vasoconstrictive response occurred. This response corrected in patients undergoing OLT. This post OLT correction produces an increase in systemic vascular resistance. This abrupt change in afterload can precipitate systolic dysfunction and heart failure. The prognosis of post liver transplant systolic dysfunction and heart failure is largely unknown. Over time the heart may adapt to this increase in afterload and have improvement of systolic function. A small set of patients undergoing transplantation at the Mayo Clinic demonstrated improvement in EF over a 15 month follow up, though never completely returning to pre-operative levels. Initial treatment should focus on treatment of CHF symptoms while monitoring for return of systolic function. ### 29 CONSEQUENCES OF SYSTEMIC VENOUS HYPERTENSION DUE TO DECOMPENSATED BIVENTRICULAR FAILURE S.S. Zaidi, A.U. Shahbaz, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN.* #### Case Report: Purpose Irrespective of its etiologic origins, elevations in systemic venous pressure lead to an engorgement of hepatic and splanchnic venous circulations to cause hepatic and gastrointestinal dysfunction. To illustrate less-well recognized consequences of systemic venous hypertension and their reversible nature, we report on a patient having recurrent episodes of decompensated biventricular failure. #### Case Report A 55-year-old African-American male with a history of heart failure due to dilated cardiomyopathy of uncertain origin with reduced ejection fraction (<30%) was hospitalized on several occasions because of his symptoms and signs of systemic venous hypertension that included elevated jugular venous pressure and tricuspid regurgitation. His hepatic and splanchnic congestion would improve with bed rest and medical therapy. On each admission, he was found to have: elevated serum B12 (1090 ± 240 pg/mL), without elevation of serum transaminases (AST, 25 ± 8 U/L; and ALT, 22 ± 6 U/L); hypoalbuminemia (2.44 ± 0.2 gm/dL); and relative lymphocytopenia (7 ± 0.7%) with normal white blood cell count (4.9 ± 0.4 K/mm3). Positive technetium-dextran70 scintigraphy was consistent with a protein-losing enteropathy. Each hospitalization led to improved clinical status and decline in B12 (580 ± 50 pg/mL) and rise in albumin (3.2 ± 0.2 gm/dL) and lymphocytes (16 ± 3.8%). When he had attained euvolemia as an outpatient (30 ± 5 days), there was evidence of continued improvement: B12, 548 ± 17 pg/mL; albumin 3.43 ± 0.05 gm/dL); and relative lymphocytes (25 ± 2%). #### Conclusion Our patient demonstrates less well-recognized consequences of systemic venous hypertension that can accompany decompensated biventricular failure. These include the release of stored B12 from the congested liver and the enteric loss of albumin and lymphocytes from the congested splanchnic territory. Serial monitoring of these parameters once elevations in systemic venous pressure and expanded intravascular volume have been eliminated serve to illustrate their reversibility. ### 30 UNEXPLAINED SPONTANEOUS LEFT MAIN CORONARY DISSECTION IN A 40 YEAR OLD FEMALE WITH NO MAJOR RISK FACTORS J. Martinez, C. Kavasmaneck, P. Kurnick *Hahnemann University Hospital, Philadelphi, PA.* #### Case Report ALG is a 40 year old female with history of dyslipidemia on statin therapy, family history of CAD, and no toxic habits. She presented to our ER due to oppressive type chest pain (10/10), diaphoresis and syncope. Her initial EKG showed ST-T segment depressions from lead V1 to V6 and intermittent RBBB. In view of her symptoms and EKG changes, she was taken to the Catheterization Laboratory for evaluation. Left Heart Catheterization revealed a left main coronary dissection extending all the was into the left anterior descending artery. Patient developed non sustained ventricular tachycardia requiring full ACLS, orotracheal intubation and electrical cardioversion. Emergency Percutaneous Coronary Intervention directed at the left main dissection was undertaken. Successful stent placement from the left main coronary into the LAD prevented any further dissection. Intra Aortic Balloon Pump was placed and the patient was admitted to the CCU. Ejection Fraction just after the procedure was 5-10% by 2D Echo. IABP could be discontinued in the next couple of days and EF improved to 40-50% just before hospital discharge. Rheumatoid factor and CRP levels were mildly elevated. However, B-HCG, ANA, DNA Ab DS, RPR, Complement 50, Histone Ab, ESR, and Homocysteine levels were all negative. This is a puzzling case of a spontaneous left main coronary dissection in a young non-pregnant woman with no apparent major risk factors or rheumatologic condition. She is still undergoing further work up to explain a reason for this event and to see if she or any family member is at risk for a future similar event. ### 31 SPONTANEOUS CORONARY ARTERY DISSECTION PRESENTING AS ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION H. Franqui-Rivera, R.G. Colacioppo-Saavedra, J. Martinez-Toro, M.R. Garcia-Palmieri *University of Puerto Rico, Toa Alta, PR.* #### Case Report A 41-year-old woman with no history of systemic illness complained of severe, oppresive retrosternal pain of sudden onset with associated with shortness of breath and nausea. An electrocardiogram revealed ST-segment elevation of leads V1 through V5. The patient is initially treated with tenecteplase, but there is no improvement in symptoms nor electrocardiographic changes. Two hours later, the patient suffered ventricular fibrillation, requiring electrical defibrillation and mechanical ventilation. She is transferred to our institution for emergency percutaneous coronary intervention. Upon arrival, the patient is found in cardiogenic shock. Coronary angiography revealed aneurysmatic dilatation of the left main coronary artery with complete dissection of the left anterior descending artery and the ramus branch, causing distal occlusion of the affected vessels. The patient was submitted for emergency Coronary Artery Bypass Graft (CABG) surgery. No risk factors for coronary artery disease were found in this patient. This case illustrates spontaneous dissection of the coronary arteries, which is a rare cause of myocardial infarction. Fewer than 200 cases have been reported since first described in 1931. This condition occurs most frequently in pre-menopausal women and is thought to be caused by hormonal changes that cause weakness of the vasa vasorum and promote hemorrhage into the media. ### 32 TOO OLD AND TOO FAST FOR TAKO-TSUBO? R. Kadari, T.Z. Haddadin, R. Brenya, S.D. Loyd, R.D. Smalligan *East Tennessee State University, Johnson City, TN.* #### Case Report Tako-tsubo cardiomyopathy is a relatively newly described syndrome first reported by Japanese authors in the 1990s. It typically presents as ST-elevation myocardial infarction without evidence of obstructive coronary artery disease in post-menopausal women with apical akinesis or dyskinesis appearing as apical ballooning. Case: An 84-year-old white female patient with no previous history of CAD presented with left-sided chest pain radiating to the back, nausea and vomiting, blood pressure of 89/46 and a severe mitral regurgitation murmur radiating to the axilla. The initial EKG showed antero-lateral ST-segment elevation myocardial infarction with Q waves. Troponin at the time of admission was 7. Left heart catheterization done immediately showed minimal CAD, global hypokinesis with anterior wall akinesis and apical ballooning, ejection fraction of 10 to 15% and severe mitral regurgitation with annular dilatation. She was placed on an intra-aortic balloon pump (IABP) and heparin drip for her severe mitral regurgitation, low cardiac output and hypotension. By the middle of that day, the patient stabilized and the IABP was removed. An echocardiogram done later that same day showed resolution of the cardiomyopathy with ejection fraction improving to 55-60% with only minimal mitral regurgitation. The patient was discharged a few days later as her clinical condition had improved considerably. Discussion: This case illustrates several unusual features compared to the typical case of Tako-tsubo cardiomyopathy which is also known as the "broken heart syndrome". First, our patient was considerably older than most patients with the syndrome (84 yo compared to 50-75 yo). Secondly, there was no obvious emotional stress around the time of the event which is more typical. Thirdly, while Tako-tsubo cardiomyopathy is generally transient and resolves over days to weeks, our patient showed dramatic reversal of the cardiomyopathy in a few hours instead of the usual longer recovery period. This occurred despite the presence of severe MR at the outset which usually portends a worse outcome. Clinicians should keep Tako-tsubo cardiomyopathy in their differential diagnosis of elderly women with AMI despite the presence of atypical features. ## **Adolescent Medicine and Pediatrics: Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 33 BREAST FEEDING DOES NOT PROTECT AGAINST URINARY TRACT INFECTION IN THE FIRST 3 MONTHS OF LIFE, BUT VITAMIN D SUPPLEMENTATION OF FORMULA FED INFANTS DOUBLES THE RISK R. Katikaneni, T. Ponnapakkam, A.Ponnapakkam, R. Gensure *Ochsner Clinic Foundation, New Orleans, LA.* #### Purpose of Study To determine if breast feeding or vitamin D supplementation protects against UTI #### Methods Used Retrospective chart review #### Summary of Results It has been reported that breast feeding protects infants against urinary tract infection (UTI). To investigate this further, we performed a chart review of infants who had urine cultures obtained within the first 3 months of life at Ochsner Hospital, New Orleans, LA, between the years 2001-2006. 40% of these children were breast fed (18.7% exclusively breast fed), similar to previously reported breast feeding rates at our hospital. 20% of all of the urine cultures tested positive. As expected, a greater percentage of urine cultures in females were positive (22.5%) vs. males (18.1%, *P* < 0.05). We next compared the rates of positive urine cultures in exclusively breast fed children (22%) with those of formula fed infants (21%). The relative risk of UTI with breast feeding versus formula feeding was 1.03 (0.58-1.82) and the relative risk of UTI with any breast feeding versus no breast feeding was 0.92 (0.58-1.45). We thus found no evidence that breast feeding protects against UTI. We were concerned that a greater percentage of breast fed infants may be receiving vitamin D supplementation, increasing rates of UTI in this group and confound our analysis. We found that vitamin D supplementation significantly increased the risk of UTI, with a relative risk of 1.76 (1.07-2.91, *P* < 0.05). However, only the formula-fed infants showed an increased UTI risk (RR = 2.24 (1.29-3.90), *P* < 0.05); neither exclusively breast fed infants (RR = 1.61(0.46-5.59)) nor infants receiving any breast milk (RR = 1.12(0.38-3.28)) showed any increased risk. This finding may have confounded earlier studies and led to the conclusion that breast feeding protects infants from UTI. Importantly, the rates of vitamin D supplementation in our population were very low (5 percent), minimizing their effect on our study's results. #### Conclusions Our data indicate that breast feeding does not protect from UTI, but supplementing formula fed infants with vitamin D increases their risk of UTI by 125%. We would therefore recommend that parents whose children are formula fed be advised against providing vitamin D supplements to their children. ### 34 NEUROBLASTOMAS: THE UMC EXPERIENCE V.R. Marlar1, C.A. Koch1, V. Vijayakumar2 * 1 University of Mississippi Medical Center, Jackson, MS and 2University of Mississippi Medical Center, Jackson, MS.* #### Purpose of Study To report the University of Mississippi Medical Center's experience on the diagnosis and tx of patients with neuroblastomas. #### Methods Used We searched the cancer registry for neuroblastomas diagnosed within the past five years. We compiled data including age at diagnosis, clinical presentation, size and location of primary tumor, stage, and histology. Staging was based on the proposed INSS staging system. Treatment course and clinical outcomes were retrospectively analyzed. #### Summary of Results We included 18 cases (12 males, 6 females; 10 white, 8 black) for which sufficient data was available. Age at diagnosis ranged from birth to 11 years (mean of 2.17 years). Most patients presented with abdominal symptoms but other presentations included neck mass, Horner's syndrome and subcutaneous nodules. One patient had opsoclonus-myoclonus syndrome. Primary sites included abdomen (13), neck (3) and chest (2). Patients were categorized as stage 1 (1), stage 2 (1), stage 3 (4), and stage 4 (11); 1 patient was diagnosed post-mortem and staging was not possible. Twelve patients are living (mean follow-up of 39.6 months), including 7 without evidence of disease; 5 patients died within a mean of 12.6 months from diagnosis; status is unknown for one patient. 11/12 alive patients had surgical resection (of which 10 received chemo and 3 received combined chemo/XRT); the one patient without surgery (stage III) did receive chemo and XRT. Of the dead pts, one received surgery/chemo/XRT, 1 received surgery/chemo and 1 received chemo/XRT; 2 died before treatment could be initiated. Amongst the 12 living patients, there were 5 black and 7 white; and amongst the 5 dead, 3 were black and 2 were white. #### Conclusions Neuroblastomas are highly variable in both presentation and behavior. About half of pts present with metastatic disease, though our rate was somewhat higher (64%). One possible explanation for this is limited access to health care (common among our patient population) and delayed diagnosis. Our mortality rate (29%) is consistent with what has been previously reported. Based on our preliminary data there seems to be no health disparity, as 7/9 white pts are alive compared to 5/8 black pts. ### 35 AN OBESITY PROGRAM FOR UNDER-SERVED PEDIATRIC PATIENTS: IS DIRECTIVE COUNSELING EFFECTIVE? A. Nash, T. Duryea, A. McDonald *Baylor College of Medicine, Houston, TX.* #### Purpose of Study Pediatric obesity has reached epidemic proportions in America. Approximately 2 million children in Texas are overweight. The purpose of the study is to assess the effectiveness of the existing obesity follow along program offered by the two Texas Children's Hospital mobile clinics, which provide medical care to uninsured, primarily Hispanic children in under-served areas of Houston. #### Methods Used The invited obese patient is scheduled to return monthly for 5 re-visits after the initial well exam (total of 6). Measurements are taken and the family/patient is interviewed regarding diet and activity. Praise is given for positive changes and advice is given regarding necessary changes. Fasting labs are offered to patients who have signs of insulin resistance or a family history of any co-morbidity of obesity. The style of intervention is directive counseling, and provision of lab evidence that the child's obesity is having a negative effect on his/her health. #### Summary of Results During 2007-2008, 94 obese patients returned for at least one visit (V 2) after the initial exam (V 1). Mean age = 10.3 yrs (4.7-17.2 yrs). Mean BMI = 26.2 (17.4-47). 81% had BMI's > 95% and 37% had BMI's ≥ 99%. Mean BMI z score was 2.03 (1.13-3.13). 82% reported some family history of a co-morbidity of obesity. 66% had signs of insulin resistance. Of the 48% who had labs, 82% had some abnormality. Only 55% returned for V3, 35% for V4, and only one patient came for all 6 visits as prescribed. Mean number of days between V1 and V2 = 34; between V1 & V3 = 76; between V1 and V4 = 120. Using the paired samples t test, mean z scores were found to be significantly lower between V1 and V2 (*P* = 0.01); V1 and V3 (*P* = 0.002); and V1 and V4 (*P* = 0.002). Using the same test, mean BMI's were only found to be significantly lower at V2 (*P* = 0.014). #### Conclusions Drop out from the program was high. Although the data do show statistically significant improvement in mean BMI and z scores, those "significant" BMI changes range from 0.14 to 0.3 points. The question is: are those changes clinically significant? The mobile clinic providers are seeking innovative, more effective ways to counsel obese children so they are empowered and motivated to make needed lifestyle changes. ### 36 CYSTIC FIBROSIS-RELATED DIABETES: A CURRENT REVIEW OF SCREENING, DIAGNOSIS, AND TREATMENT M. Rayas *University of Texas Health Science Center in San Antonio, San Antonio, TX.* #### Purpose of Study Cystic fibrosis is the most common life-threatening autosomal recessive disease of Caucasians, with the incidence of 1 in 3000 births in the United States. Cystic fibrosis patients are now living longer due to the improvement in pulmonary and nutritional care. The longer life expectancy has led to an increase in the prevalence of comorbid conditions such as cystic fibrosis-related diabetes. Cystic fibrosis-related diabetes shares features of both Type I DM and Type II DM, and therefore requires a unique approach to management. Screening and diagnosing cystic fibrosis-related diabetes has been previously proposed but is not routinely seen in practice. Treating cystic fibrosis-related diabetes usually requires insulin therapy, but recent research has focused on utilizing oral agents. This article reviews the literature in regards to screening, diagnosing, and treating cystic fibrosis-related diabetes in the inpatient population. #### Methods Used The review included, but was not limitied to, searching Cochrane, Pubmed, and Ovid databases. #### Summary of Results Screening for cystic fibrosis-related diabetes should be performed on all cystic fibrosis patients 14 years of age or older when hospitalized. Diagnosing cystic fibrosis-related diabetes should be conducted using current ADA guidelines for diagnosing diabetes mellitus proposed at the 1998 North American CFRD Consensus Committee. The treatment of cystic fibrosis-related diabetes should involve insulin therapy. A physician must take into account the diet of the cystic fibrosis patient, such as nighttime G-tube feeds, when deciding between short-acting vs. long-acting insulin therapy. A multicenter randomized control trial of insulin therapy vs. oral agents needs to be conducted to determine the efficacy of oral agents. #### Conclusions Reviewing the literature in regards to screening, diagnosing, and treating cystic fibrosis-related diabetes in the inpatient population will promote the development of a future nationwide inpatient protocol. ## **Adult Clinical Case Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 37 ESCHERICHIA COLI NECROTIZING FASCIITIS IN A TRANSPLANT PATIENT T.D. Alford, G. Teran, S.P. Mannem, R.D. Smalligan, R., Kuriacose, W. Shams *East Tennessee State University, Johnson City, TN.* #### Case Report Skin infections are most often caused by Gram-positive bacteria. We report a case of necrotizing fasciitis (NF)caused by E. coli in a renal transplant patient. Case: A 36yo male with hx of renal transplant and failing second transplant presented with redness, edema, and pain in his right arm without fever or chills. He had recently been treated for E. coli urosepsis and MRSA pneumonia. PMH: ESRD s/p transplantation 12 yrs prior, diabetes, HTN, pulmonary embolus, gastric bypass surgery, and chronic pancreatitis. Meds: prednisone, darbepoetin alfa, mycophenolate mofetil, esomeprazole, oxycodone, and warfarin among others. Patient is disabled, lives with his wife and denies alcohol, tobacco, or illicit drug use. PE: BP 94/57, P 98, T 37, RR 16, O2 sat 90% on RA. HEENT, CV, ABD exams normal; lungs: few crackles without rales; extremities: erythema of right upper extremity (RUE) from elbow to hand, tender to palpation with some bullae and no crepitis. Labs: gluc 129, BUN 64, Cr 4, WBC 4.3, Hct 27, plt 125k; wound and blood cultures positive for E. coli. Despite antibiotics, the patient developed necrotizing fasciitis requiring surgical debridement and later skin grafting. Discussion: Skin infections are not frequent in transplant recipients but when they do occur are most often due to Gram-positive organisms such as Staphylococcus and Streptococcus species. We describe here a renal transplant recipient with a failing second transplant requiring higher doses of immunosuppressants who presented with E. coli urosepsis and erythematous-bullous lesions that rapidly evolved to hyperacute necrotizing fasciitis. Gram-negative bullous cellulitis with necrotizing fasciitis is a rare condition associated with a poor prognosis which can be lethal if not identified and treated promptly. Treatment includes aggressive surgical debridement, IV antibiotics and consideration of hyperbaric oxygen therapy. Physicians caring for transplant or other immunosuppressed patients should keep necrotizing fasciitis in mind with any bullous cellulitis presentation since early diagnosis and aggressive therapy may be lifesaving as it was in our case. ### 38 A CASE OF LEUCOCYTOCLASTIC VASCULITIS DUE TO GLARGINE INSULIN H. Bhakthavatsalam, J.M. Dungao, M. Margulis, N. Selvanayagam *Coney Island Hospital, Brooklyn, NY.* #### Case Report A 57 year old man with two years history of Diabetes Mellitus presented with left great toe gangrene and rash over lower extremities for three days. He denied trauma. The skin lesions were purpuric, non itchy and nontender. Patient was on glargine insulin for his Diabetes but non compliant and had stopped taking for atleast past six months. He started on Glargine insulin after he developed the toe ulcer, just a day prior to developing the rash on the legs. The gangrenous toe was amputated and antibiotics were started for osteomyelitis confirmed by MRI. Patient was continued on Glargine insulin for glycemic control. Patient did not have fever or other systemic signs of sepsis but the purpura was worsening. Laboratory tests including CBC, renal, liver functions,C3/C4,ANA,ANCA were normal. Skin biopsy done revealed Neutrophilic Leucocytoclastic Vasculitis. As per his history since the purpura developed after restarting glargine insulin, this insulin preparation was stopped and changed to Human Regular/NPH insulin. The skin lesions regressed in the next two days and completely resolved in 2 weeks. Patient was discharged home on iv antibiotics to complete the course of 6 weeks for osteomyelitis. Conclusion: Cutaneous leucocytoclastic vasculitis presents as palpable purpura mostly localized to the lower extremities, often accompanied by abdominal pain, arthralgia and renal involvement. The clinical diagnosis is confirmed by skin biopsy. Once diagnosis is confirmed emphasis should be made on the search for an etiological factor. The prognosis depends on the severity of internal organ involvement. In case of drug induced vasculitis, the drug should be removed immediately. Vasculitic skin lesions secondary to drugs are implicated in 10% to 30% cases. The common agents are Penicllins, Sulfonamides, Diuretics, Antihypertensives, Antiarrhythmics, Allopurinol, Cimetidine, Hydantoins. As per literature, Insulin is rarely implicated in causing leucocytoclastic vascultis. In our patient it was clearly attributable to glargine insulin since clinical improvement occurred soon after switching to another insulin preparation and also to be noted, patient did not develop any reaction to insulin Regular/NPH. ### 39 WANING IMMUNITY AND WANING STRENGTH V. Gangadharan1, J. Myers2,1, P. Patel2,1, R.D. Smalligan1 * 1East Tennessee State University, Johnson City, TN and 2East Tennessee State University, Johnson City, TN.* #### Case Report A treatment experienced HIV positive 49-year-old woman presented with headache, chills, photophobia, neck pain and a painful rash. Her past history was negative except for hepatitis C and HIV for which she was on Truvada and Lexiva. Physical examination was normal except for painful vesicular lesions on her face, neck, upper torso and extremities with a benign neurological exam. Initial lab work showed WBCs of 2,700, CD4 count 186, HIV viral load of 6,000 and serum chemistries within normal limits. An LP with CSF analysis showed 30 WBC with 81% lymphocytes, normal glucose, and elevated protein and was negative for Cryptococcal antigen, West Nile virus, Varicella-Zoster virus (VZV) and HSV. CXR and CT Head were normal. The patient soon developed acute onset of right lower extremity weakness with diminished reflexes at the knee and ankle. An MRI of the brain and spine showed a focal, mildly expansile lesion of the cord between T9-T11 suggestive of inflammation or tumor. CSF PCR for VZV later returned positive confirming the diagnosis. Intravenous acyclovir had been started empirically and was thus continued. The patient gradually showed improvement with almost complete resolution of her weakness. Discussion: Herpes zoster can occur in any host but is often more pronounced in the elderly and immunocompromised. Various studies have demonstrated an incidence of Zoster as high as 30% in the HIV population as compared to the general population (10%). The most common manifestation is a vesicular rash in a dermatomal distribution, but several neurological complications can also be seen ranging from aseptic meningitis to rare cases of transverse myelitis (<0.5%) as seen in our patient. Treatment of Zoster related transverse myelitis is with acyclovir which provides gradual symptomatic improvement if started promptly. Clinical trials are also underway to examine the utility of the Zoster Vaccine in HIV patients to prevent such complications. In conclusion, early recognition and treatment of this uncommon complication of VZV reactivation is essential so that appropriate treatment can be initiated and severe neurologic damage averted, especially in the most vulnerable of populations: the immunocompromised. ### 40 CLOPIDOGREL-INDUCED MIXED HEPATOCELLULAR AND CHOLESTATIC LIVER INJURY: AN UNUSUAL COMPLICATION R.K. Goyal *Lenox Hill Hospital, NY, New York, NY.* #### Case Report Drug-induced hepatotoxicity is the most common cause of acute liver failure in the United States. A high index of suspicion is required to diagnose drug-induced liver injury. We present second case of clopidogrel-induced mixed hepatocellular and cholestatic injury confirmed with positive rechallenge test. A 78-year-old woman was admitted for right upper quadrant abdominal pain and jaundice. Her past history included CAD, GERD, hypertension and gout with no prior liver disease and alcohol use. She was started on aspirin 325 mg/day and clopidogrel 75 mg/day after PCI with drug-eluting stents 3 weeks ago. Her regular medications were valsartan, amlodipine, metoprolol, simvastatin, lansoprazole and allopurinol. On examination, she had stable vital signs with pale conjunctivae and icterus sclera. Abdomen was soft with mild tenderness over right upper quadrant. Her hemoglobin was 8.6 g/dl and creatinine 1.9 mg/dl. LFTs were elevated with AST 179 U/L, ALT 234 U/L, alkaline phosphatase 1011 U/L and bilirubin 7.3 mg/dl. One unit of packed red blood cells was transfused. Clopidogrel, amlodipine, simvastatin and valsartan were discontinued. Patient was started on intravenous fluids. Her hemoglobin, ARF and LFTs improved. Abdominal imaging studies ruled out any obstruction in common bile duct. Clopidogrel was reintroduced on day 5 in view of risk of thrombosis of her drug-eluting stents. LFTs increased rapidly thereafter. Results for infectious mononucleosis and hepatitis A, B and C serology, ANA, anti-smooth muscle antibody, ceruloplasmin, CEA and CA19-9 were negative. Drug-induced liver injury was suspected and clopidogrel was discontinued indefinitely. Liver enzymes after two weeks returned to normal. Clopidogrel is a well tolerated antiplatelet agent with bleeding, rash, vomiting and diarrhea as common side effects. Clopidogrel-induced hepatotoxicity is a rare complication and is difficult to diagnose in presence of polypharmacy and lack of liver biopsy and rechallenge test. A high clinical suspicion with positive rechallenge test and exclusion of other obvious causes confirmed diagnosis of clopidogrel-induced hepatic injury in our patient. Physicians should be highly vigilant to diagnose drug-induced liver injury, especially for drugs with rare hepatotoxicity such as clopidogrel. ### 41 HEPARIN-INDUCED ACUTE INTERSTITIAL NEPHRITIS: A CASE REPORT S. Sadhu1,2, O. Lenz1 * 1University of Miami Miller School of Medicine, Miami, FL and 2Jackson Memorial Hospital, Miami, FL.* #### Purpose of Study Heparin has been known to occasionally cause eosinophilia. However, there is no reported case in the literature of interstitial nephritis secondary to heparin. We hereby report the first case of heparin-induced allergic interstitial nephritis. #### Methods Used This is a case report. #### Summary of Results The patient is a fifty-one year old African-American man with a history of diabetes mellitus type 2, hypertension, diabetic nephropathy with nephrotic syndrome and chronic kidney disease, non-adherent to all medications, who presented to the hospital with hypertensive urgency and worsening leg swelling. His blood pressure was adequately controlled with oral lisinopril, labetalol, nifedipine and furosemide and he was placed on unfractionated heparin for deep venous thrombosis prophylaxis. After remaining stable for a few days after admission, the serum creatinine began to rise and peaked at 6.5 mg/dl on the sixteenth hospital day from 4.5 mg/dl at admission. The eosinophil count, which had been normal at admission, also rose, parallel to the serum creatinine, to a peak of 18%. Gallium-67 citrate scintigraphy demonstrated bilateral symmetrical uptake by both kidneys. Acute interstitial nephritis and drug-induced eosinophilia were suspected and heparin was discontinued. All other medications were unchanged. The serum creatinine and eosinophilia began to trend down in twenty-four hours. On follow-up in two weeks, the serum creatinine stabilized close to baseline and eosinophilia had completely resolved. #### Conclusions Heparin can cause acute interstitial nephritis along with eosinophilia. On the Naranjo adverse drug reaction probability scale, this is a probable reaction. Since heparin is one the most commonly used medications used in hospitalized patients, it is important to recognize this serious adverse event in the appropriate clinical context. ### 42 TWIDDLER SYNDROME - A RARE BUT POTENTIALLY LETHAL CLINCAL ENTITY Y. Yaqub, M. Phy, J. Suarez, A. Perez-Verdia, K. Nugent, P. Sutthiwan *Texas Tech University Health Science Center, Lubbock, TX.* #### Purpose of Study First described in 1968, pacemaker twiddler syndrome is a rare but potentially lethal clinical entity that refers to the permanent malfunction of pacemaker due to the patient's manipulation of the pulse generator. Study purpose was to determine the clinical and pacing characteristics and short term outcomes associated with twiddler syndrome during a 24 month (July 05-07) period at a university hospital. #### Methods Used Retrospective chart review was done after obtaining IRB approval. #### Summary of Results Four patients presented with twiddler syndrome with complaints ranging from palpitations, dyspnea or fever. The mean age of these patients was 76.3 years, and all were men. The clinical characteristics and pacing variable are shown in the Table. Episodes of non-sustained ventricular tachycardia were found in all patients. Loss of capture and inadequate pacing was seen on admission EKG. Mean QRS duration at admission was 156.3 milliseconds (r = 105-200 ms).All had underlying coronary artery disease and ischemic cardiomyopathy. Three of the four patients had dementia (75%, *P* = 0.024). The mean ejection fraction was 23.5% (r = 20-29%). The pulse generator was infected in two (50%) patients. Femoral approach was used for temporary pacemaker insertion in all cases. Duration of temporary pacing as a bridge to permanent pacemaker was 3.25 days (range = 2-5 days). Subsequently biventricular permanent pacemakers or ICD were placed. The mean duration of stay was 4.5 days. View this table: [Table7](/content/57/1/301/T7) #### Conclusions Twiddler syndrome is a rare but a dangerous condition that results in lead dislocation or loss of capture with potential mortality. 75% of twiddler patients in our study had underlying dementia which could predispose to unintended pulse generator manipulation and lead dislodgement. We should have high index of suspicion of this potentially lethal condition in elderly patients with PPM/ICD's with underlying dementia presenting with arrthymias, including non-sustained ventricular tachycardia. ### 43 INFLAMMATORY MYOFIBROBLASTIC TUMOR OF THE HEART. A CASE REPORT A.A. Zia1, S. Alsafwah1, A. Munir1,2 * 1University of Tennessee Health Science Center, Memphis, TN and 2Veterans Administration Medical Center, Memphis, TN.* #### Case Report: Clinical History We describe the case of a 25-year-old African-American male who was admitted to one of our teaching hospitals with a 6-month history of intermittent chest pain and shortness of breath. Transthoracic echocardiography showed a 2x6 cm right ventricular mass. The patient was taken to the operating room, but the mass proved technically impossible to remove. Intraoperative biopsy specimens were taken. #### Surgical Pathology Fibrovascular tissue with florid chronic inflammation and histiocytic reaction. Immunohistochemical stains for actin and CD-68 were positive. Based on these findings a diagnosis of inflammatory myofibroblastic tumor was made. #### Discussion Inflammatory myofibroblastic tumor (IMT) is a rare lesion in adults consisting mainly of spindle-shaped mesenchymal and inflammatory cells. IMT most commonly involves the lung and the orbit, but it has been reported to occur in nearly every site in the body. IMT is probably a neoplasm rather than a post-inflammatory process because of cytogenetic clonality, recurrent involvement of chromosomal region 2p23, occasional aggressive local behavior, and its metastatic nature. Histochemically and immunochemically IMT is characterized by the expression of vimentin, smooth muscle actin, and cytokeratins, corresponding to that of myofibroblasts along with other inflammatory markers. In recent years attention has focused on the putative role of Human Herpes virus 8 and Epstein Barr virus in the activation of proto-oncogenes and anti-apoptotic factors leading to neoplastic transformation to IMT. The definition and characterization of IMT is an evolution in progress. Though rare, this neoplasm often afflicts younger patients and should be kept in the differential diagnosis of undiagnosed masses in various locations as early diagnosis may lead to resection and cure. Delay in diagnosis may lead to unresectability as was unfortunately the case in our index patient. ## **Allergy, Immunology, and Rheumatology Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 44 QUALITY OF LIFE IN PATIENTS WITH MIXED CONNECTIVE TISSUE DISEASE USING SHORT FORM-36: COMPARISON TO A POPULATION WITH SYSTEMIC LUPUS ERYTHEMATOSUS L.E. Ayala1,2, M. Acosta1,2, M. Perez1, M. Maldonado1,2, R.W. Hoffman1,2, C.J. Lozada1 * 1 University of Miami/Jackson Memorial Medical Center, Miami, FL and 2 Miami Veterans Affairs Medical Center, Miami, FL*. #### Purpose of Study Physical, mental and social disabilities are among the most significant impairments caused by rheumatic disease. Our purpose was to understand the effects of Mixed Connective Tissue Disease (MCTD) on quality of life and compare them to those in patients with Systemic Lupus Erythematosus (SLE) where Short Form-36 (SF36) has been used extensively. #### Methods Used The SF36 was administered to consecutive patients with MCTD or SLE upon enrollment in our prospective, observational, longitudinal study in order to assess health related quality of life (HRQOL). SF36 is a multipurpose survey that measures patient centered general health outcomes. The cohort included widespread representation of different ethnic/racial groups. The MCTD cohort was 55% Hispanic, 35% African American and 10% Caucasian. The SLE group was 51% Hispanic, 44% African American and 6% Caucasian. #### Summary of Results The cohorts were similar in age and disease duration at enrollment. HRQOL was diminished in both patient groups across all 8 domains of the SF36. It was also decreased as measured by the Physical Health (PH) and Mental Health (MH)Summaries. For patients diagnosed with MCTD, all 8 domains of the SF36 were below average by >1SD. Physical Health summary had a score of 39.1 while Mental Health summary was 37.3. The difference was not statistically significant. In contrast in those with SLE, we found only 6 out of the 8 domains with an average of 1SD below the mean. Patients with MCTD had worse HRQOL than patients with SLE when evaluating mental health and vitality. #### Conclusions Patients with MCTD have decreased HRQOL when compared to the average healthy control population. The differences are similar to those seen in SLE although in those with MCTD there were trends suggesting worse mental health and vitality. Although, these differences were not statistically significant, they could be clinically relevant. In addition, MH summary scores were the most affected in patients with MCTD and PH summary scores the most affected in those with SLE suggesting subtle but perhaps clinically relevant differences in the effects of these diseases on HRQOL. ### 45 X-LINKED AGAMMAGLOBULINEMIA WITH ISOLATED IGM DEFICIENCY M.C. Bell1, T.T. Perry1,2, A.M. Scurlock1,2, S.M. Jones1,2, * 1University of Arkansas for Medical Sciences, Little Rock, AR and 2Arkansas Children's Hospital, Little Rock, AR.* #### Case Report Purpose of Study: Case review of three brothers with X-Linked Agammaglobulinemia (XLA) caused by bruton's tyrosine kinase (BTK) gene mutation with atypical laboratory findings. Methods Used: A retrospective chart review was used to describe cases of three brothers with recurrent sinopulmonary infections. Summary of Results: LM presented at age 6.5 years with pneumonia. His history was significant for Kingella kingae osteomyelitis (18 months) and a previous episode of pneumonia (6 years). Immunologic workup revealed low absolute circulating B cells, absent IgM (<10 mg/dL), and normal IgG, IgA, and IgE. Pre and post vaccination titers revealed a normal response to diptheria and tetanus but no response to 14/14 pneumococcal serotypes. LM was started on monthly intravenous immunoglobulin (IvIg) and later switched to subcutaneous immunoglobulin (ScIg) therapy. LM, now 9 years old, has had no infections since starting immunoglobulin therapy. KM presented at age 2 years after bilateral pressure equalization tubes (PET) placement. His history included chronic rhinorrhea, 1 episode each of pneumonia and bronchiolitis, and recurrent otitis media. KM's immunologic testing revealed low absolute B cells, no response to pneumococcal vaccine, absent IgM, and normal IgG, IgA, and IgE. KM, now 4 years old, has continued to have recurrent otitis media requiring a second set of PET and antibiotics despite monthly IvIg. BM presented with recurrent otitis media and gastroenteritis requiring hospitalization at age 16 months. BM had low absolute B cells, absent IgM, and normal IgG, IgA, and IgE. BM was started on IvIg therapy and has done well. Genetic testing for XLA was obtained on the brothers and sequencing revealed a 167T > C mutation in the BTK gene causing an Ile56Thr missense mutation (previously described). A fourth brother has had no clinical recurrent infections and normal BTK gene sequence. Maternal BTK gene profile is pending. Conclusions: XLA is a rare humoral immunodeficiency due to BTK gene mutations resulting in a paucity of circulating B cells and low-absent serum immunoglobulins. To our knowledge, we are the first to report a family cohort of XLA with an isolated low IgM in the presence of normal IgG, IgA, and IgE. ### 46 ADULT-ONSET HENOCH-SCHONLEIN PURPURA WITH POSITIVE C-ANCA [ANTI-PROTEINASE 3] E.R. Boulis, V. Majithia, R.W. Mc Murray, *UMC, Jackson, MS.* #### Case Report INTRODUCTION: Henoch-Schonlein Purpura (HSP) is a vasculitis associated with IgA deposition and is characterized by arthralgia, purpuric rash, abdominal pain and nephropathy. Anti-neutrophil cytoplasmic antibodies (ANCA) are present in many isotypes (IgM, IgG or IgA). Two common patterns, cytoplasmic (c-ANCA) react with proteinase 3 (PR3) is specific for Wegner's granulomatosis and perinuclear (p-ANCA) react with myeloperoxidase (MPO) seen in microscopic polyangiitis. In HSP and IgA nephropathy, IgA ANCAs and IgG p-ANCA have been reported in several cases. But IgG c-ANCA has only been reported twice. We report a case of biopsy proven HSP associated with IgG c-ANCA. CASE: A 51-year-old white male with unremarkable medical history presented with a two week history of diarrhea, abdominal pain, joint aches and rash in his legs extending to his whole body. On exam he had diffuse palpable purpura, mild epigastric tenderness, edema on the dorsum of his hands and feet. Abnormal laboratory studies included elevated WBC count, transaminases, alkaline phosphatase and bilirubin as well as hematuria and pyuria. 24-hour urine protein was 413 mg. He had a positive c-ANCA by immunofluorescence (IFA), confirmed to be IgG anti-PR3 by ELISA at 14 U/ml. Rest of the studies including renal functions, blood counts, coagulation tests, p-ANCA, hepatitis serology, complements, cryoglobulins, cultures and heart echo were normal. Gall bladder ultrasound showed acute cholecystitis. Skin biopsy of recent lesions revealed leukocytoclastic vasculitis with IgA and C3 deposition by IFA. He was treated with intravenous antibiotics, ERCP guided papillotomy and oral prednisone 1 mg/kg/day. Six weeks later, he had complete resolution of his rash, systemic symptoms and a stable creatinine. CONCLUSION: Our case highlights that IgG c-ANCA can be found in HSP, despite being more specific for Wegner's graulomatosis. It is important to make a correct diagnosis as the course and treatment are different. Steroids only were used in our patient with a good outcome, while steroids and cyclophosphamide were required in the previous two reported cases. Till the causality link between IgG c-ANCA and IgA related disease gets established with further studies, we suggest closer monitoring of renal functions and urine analysis in the setting of these patients. ### 47 ANAPHYLAXIS DUE TO GADOLINIUM: A CASE REPORT A. Fiorillo, P. Kumar, *Lousiana State University, New Orleans, LA.* #### Case Report Radiocontrast media are considered generally safe and most reactions are mild, however serious reaction can occur. Gadolinium is commonly used for MRI imaging and in the past was considered a benign compound. Although rare, gadolinium can cause serious adverse reactions as illustrated by the case described below. A 48 year female with a past medical history of hypertension was admitted with lip swelling, left sided tingling and numbness of her face. The patient was presently taking an angiotensin converting enzyme inhibitor (ACE) and was admitted for ACE induced angioedema. In addition to her lip swelling the patient described numbness and tingling in her left upper extremity. There was concern that this patient may be having a stroke, therefore an MRI with gadolinium was ordered. Within minutes of receiving a gadolinium compound, Gadopentate diglumine (Magnevist), the patient began having generalized pruritus which progressed to difficulty swallowing, shortness of breath and unresponsiveness. Advanced life support (ACLS) was initiated and the patient recovered without any further complications. The patient had an elevated tyrptase level at 66 ng/ml (ref: 2-10 ng/ml) which was drawn immediately after the reaction. Tryptase levels drawn at base line was 6 ng/ml. Serum complement C4 level, C1Q, and C1 esterase inhibitor was all within normal limits. ImmunoCap for latex was also negative. In addition the patient reports having received aspirin in the emergency room and an aspirin challenge performed on follow-up visit was negative. The patient was instructed to avoid all radiocontrast media and her ACE inhibitor was changed to a calcium channel blocker. She was asymptomatic during several follow-up visits. Reactions to gadolinium are rare with the overall incidence of allergic reactions is 0.004-0.7%. The incidence of severe a severe anaphylactoid reactions are thought to be even less common with reactions ranging from is 0.001-0.02%. The highest risks are patients with previous reactions to gadolinium contrast and possibly patients with previous reactions to iodinated radiocontrast media. We report a rare case of anaphylaxis due to gadolinium. ### 48 COMPLICATIONS ASSOCIATED WITH TOXOCARA CANIS INFECTION IN THREE PEDIATRIC PATIENTS C.L. Freeman, A.M. Scurlock, S.M. Jones, T.T. Perry *University of Arkansas for Medical Sciences/Arkansas Children's Hospital, Little Rock, AR*. #### Case Report Purpose of Study: To describe a cohort of complicated cases of pediatric toxocariasis. Methods Used: Retrospective chart review of three patients with Toxocara canis infection. #### Summary of Results Patient 1 was diagnosed with visceral larvae migrans (VLM) at age 11 months following a clinical course complicated by febrile seizures, rash, vomiting, diarrhea, cough, respiratory failure and eosinophilia (peak absolute eosinophil count (AEC) >55,000 mm3). Two yearts after initial diagnosis, he continues to have eosinophilia, despite treatment with mebendazole and daily oral corticosteroids (0.15 mg/kg/d). Primary hypereosinophilic syndrome has been ruled out in this patient with fluorescence in-situ hybridization (FISH) being negative for deletions at the CHIC2 locus (chromosome 4q12) as well as no observed abnormalities of the platelet-derived growth factor receptor α (PDGFRA) or Fip1-like 1 (FIP1L1). Patient 2 presented with left exotropia at age 3 years, and was subsequently diagnosed with ocular larvae migrans (OLM). Clinical course has been complicated by urticaria, chronic rhinitis, mild eosinophilia (AEC 1415) and cataract formation, requiring surgical intervention, despite intraocular steroids. Patient 3 was diagnosed with toxcariasis at age 3 years after presenting with fatigue, lymphadenapathy, and eosinophilia (peak AEC 9568 mm3). One year after diagnosis and treatment with mebendazole, she has persistent uncontrolled asthma and eosinophilia despite daily oral corticosteroids (2 mg/kg/d) and anti-parasitic treatment. She has also been evaluated for primary hypereosinophilic syndrome and FISH for deletion at the CHIC2 locus was not detected. #### Conclusions Clinical complications of Toxocara canis infection can be variable, and clinical presentations often parallel atopic diseases. A high index of suspicion is required for early diagnosis to prevent tissue pathology due to release of toxic eosinophil mediators. Further studies are vital to determine the factors that predispose to chronic disease complications, persistent eosinophilia, and steroid resistance, including evaluation of genetic susceptibility of the host to infection or atopy, timing/duration of infection, and treatment modalities utilized. ### 49 HUMIDITY AS AN EXACERBATING FACTOR FOR ASTHMA M. Jhaveri1, J. Temprano2, A. Branscum1, D. Hayes3, * 1University of Kentucky, Lexington, KY; 2University of Kentucky, Lexington, KY and 3University of Kentucky, Lexington, KY.* #### Purpose of Study To identify humidity as an exacerbating factor for subjects with both asthma and allergic rhinitis compared to subjects with allergic rhinitis alone. #### Methods Used Retrospective chart review of patients seen in the Allergy and Immunology Clinic between August, 2005 and December, 2007 was done. Patients were divided into two groups: asthma with allergic rhinitis (cases) and allergic rhinitis alone (control). Data was collected on demographic variables, humidity history, medications used, allergic sensitivity to molds and house-dust mite and spirometry results in both groups. Severity of asthma is categorized on basis of medications used (Mild: Nasal steroids and Bronchodilators, Severe: Inhaled steroids and Leukotriene antagonists). Univariate analysis was performed on baseline characteristics of subjects. Odds ratios and their corresponding 95% confidence intervals were estimated using conditional logistic regression with adjustment for other variables. #### Summary of Results Data was collected from 205 patients of whom 62% are cases. About 88 (70%) cases reported humidity as an exacerbating factor for asthma compared with only 39% of controls (*P* < 0.0001). Multiple logistic regression analysis showed that cases were more likely to report humidity as an exacerbating factor independent of stratification by allergic sensitivity to molds and house-dust mite as compared to controls (*P* = 0.3326). Asthma patients reported humidity as an exacerbating factor irrespective of their severity (*P* = 0.9559). #### Conclusions Our findings suggest that humidity is an exacerbating factor for asthma, even after controlling for molds, house dust mite and asthma severity. ### 50 PARANEOPLASTIC LIVEDOID VASCULITIS AS THE FIRST MANIFESTATION OF A SEQUAMOUS CELL CARCINOMA OF THE PHARYNX D. Kadaria, H. Alshayeb, F. Abu Al Rub, C. Clark, B. Weber *University of Tennessee, COM, Memphis, TN.* #### Case Report Livedoid vasculitis(LV) is a vascular disorder mostly affecting females characterized by chronic, recurrent, painful cutaneous shallow ulcerations affecting the lower extremities. Histologic features include hyalinizing vascular changes of the subintimal layer of dermal blood vessels, typically with minimal inflammation. Literature review revealed a few reported cases of Livedoid vascultis in association with hematological and solid organ malignancies. This report describes a patient who presented with (LV), all possible associated hypercoagulable conditions were ruled out. The leg ulcers did not improve desipte wound care and medical treatment. One year later, the patient was diagnosed with pharyngeal sequamous cell cancer. After one month of chemoradiation, (LV) completely resolved. A 54 year old a smoker female with pmhx of rheumatoid arthritis presented with a 2wk history of painful ulcers on the dorsum of both legs. She did not notice any weight loss, decreased appetite, fever, leg or Joint swelling or worsening of her arthralgis, or any gaterointestinal, cardiorespiratory or genitourinary symptoms. Temprature:37, Bp: 130/75, HR: 85, no lymph nodes were palpable, respiratory, cardiovascular, abdominopelvic exams were normal. Leg exam showed tender erythematous superfecial ulcers on the dorsum of both legs with no swelling or varicose veins. Labratory workup revealed a WBC:11, HTC:40, Platlet:345, Cr:1.2,Albumin:4.2,normal liver transaminases. RF was Positive, ANA, Anti-ds DNA, Antiphospholipid, anticardiolipin ab, C-ANCA,P-ANCA,HIV ab, HCV ab, HBsag were all negative. Cryoglobuins and homocysteine were undtectable. Factor V leiden and prothrombin G20210A gene mutations were absent. Protein S and C levels were normal. Doppler US of both legs was negative for DVT. Biopsy of the lesions confirmed the diagnosis of Livedoid vasculitis. CT chest, abomen and pelvis were normal. Despite wound care and treatment with pentoxyphilline, dipyridamole, warfarin,steroids, the leg ulcer did not improve. One year later the patient was diagnosed with pharyngeal cancer as a work up of a new left tonsiller mass. After one month of chemoradiation of her cancer, the Livedoid reticularis completely resolved with residual atrophic scars. ### 51 KELLEY-SEEGMILLER SYNDROME AND A THE EFFECTS OF A LATE DIAGNOSIS K.L. McMullan, J.D. Wofford *University of Mississippi Medical Center, Jackson, MS.* #### Case Report Kelley-Seegmiller Syndrome is a well described X-linked deficiency of HGPRT (Hypoxanthine-guanine phosphoribosyl transferase), an enzyme involved in purine metablolism. This syndrome leads to a spectrum of phenotypes similar but less intense than those described in the related Lesch-Nyhan Syndrome. Awareness of Kelley-Seegmiller Syndrome is important for early diagnosis, treatment, and counseling to improve morbidity from the disease. A 54 year old man was admitted for a debilitating gout flare; movement caused severe pain. He reported no fever or chills. Baseline function included the ability to feed and groom himself. Past medical and surgical history was significant for severe tophaceous gout, acute renal failure, removal of multiple gouty tophi, and finger and toe amputations. Medications were Colchicine, allopurinol, and Indocin. One brother had gout. He had a prior history of alcohol use. On physical exam he was cachectic, in moderate distress, tachycardic, with multiple, large ulcerating tophi on all extremities proximally and distally. Neurologic exam was normal. Labs: BUN/Creatinine 36/1.5, uric acid level 12.5. Kelley-Seegmiller Syndrome usually presents in adolescence or early adults with symptoms ranging from gouty tophi with or without nephrolithiasis to mild neurologic disorder. These patients do not self mutilate. Diagnosis consists of HGPRT deficiency (not absence) with elevated blood and urine levels of uric acid. Pathogenesis appears to come from mutations in the gene encoding HGPRT resulting in proteins of the same length but decreased function, separating it from Lesch-Nyhan Syndrome in which mutations change protein length. At age 36, our patient's 24 hour urine uric acid level was elevated at 904 mg with a normal renal ultrasound; baseline serum uric acid was elevated. Genetic testing was sent at age 48 and HGPRT level was deficient at 17 (low normal 200) with 8.5% HGPRT activity remaining. He experienced difficulty related to tophi and decreased renal function. Had a genetic deficiency been diagnosed early, morbitity secondary to decreased kidney function and tophi may have decreased with proper counseling and treatment. If a young patient exhibits signs of severe gout and tophi, consider genetic deficiency to improve long term morbidity. ### 52 MYASTHENIA GRAVIS PRESENTING AS WEAKNESS IN A RHEUMATOID ARTHRITIS PATIENT A. Singh, V. Majithia *University of Misissippi, Jackson, MS.* #### Case Report Introduction: Myasthenia Gravis [MG] is characterized by a fluctuating degree and variable combination of weakness in ocular, bulbar, limb, and respiratory muscles. Occurrence with rheumatoid arthritis [RA] is rare, especially without use of D-penicillamine. Case Presentation: A 25 years old African American female with history of RA diagnosed in 2004, was admitted with 4 month history of progressive, diffuse weakness since the delivery of her child. She had difficulty with activities of daily living including caring for her baby. Her RA had improved after restarting her methotrexate, prednisone and hydroxychloroquine. She denied any visual problems, muscle soreness, dysphonia, dysphagia or dysarthria. She had multiple ER visits for falls. Her examination was significant for fluctuating weakness in extremities. No focal deficits were evident. Her laboratory tests showed high titres of CCP antibodies but others including CPK, aldolase, TSH, hepatitis panel, HIV, APLS panel were unrevealing. A bedside EMG revealed evidence of neuromuscular transmission defect of post synaptic variety and her tensilon test was positive. Acetylcholine receptor Antibodies were present in high titres[217 nmol/L]. She was initially treated with Pyridostigmine bromide and prednisone in incremental doses with good clinical relief. Discussion: MG is the most common disorder of neuromuscular transmission, with fluctuating skeletal muscle weakness, often with true muscle fatigue. Fifty percent of patients present with ocular symptoms of ptosis and/or diplopia, fifteen precent present with dysarthria, dysphagia, and fatigable chewing. Symptomatic treatment with pyridostigmine is the main stay of therapy. Immunotherapeutic drugs are commonly needed including prednisone, azathioprine, and mycophenolate. Intravenous immunoglobulins and plasmapheresis have been used in severe cases like myasthenic crisis. Patients with thymoma clearly benefit from thymectomy. Conclusion: The differential diagnosis for weakness in RA patient can be vast including inflammatory myositis, viral myositis, drug induced, thyroid disease, motor neuron diseases like ALS, myopathies and muscular dystrophies. Our case highlights the rare occurrence of second autoimmune disease as a cause of weakness in RA patient. ## **Cardiovascular Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 53 THE RELATION OF C-REACTIVE PROTEIN TO PERIPHERAL ARTERIAL DISEASE IN AFRICAN AMERICANS: (THE JACKSON HEART STUDY) K. Agrawal1, H.A. Taylor1, J.H. Lee1, E.J. Benjamin2, H.S. Nagarajarao1, T.E. Samdarshi1, E.R. Fox1 * 1University of Mississippi Medical Center, Jackson, MS and 2Boston University, Boston, MA.* #### Purpose of Study There are limited data on the role of systemic inflammation as an early marker of peripheral arterial disease (PAD) in African Americans despite the higher disease burden and mortality rates in this population. We investigated the relation of C-reactive protein (CRP) to ankle-brachial index (ABI) defined peripheral arterial disease (PAD) in the population-based cohort of the Jackson Heart Study. #### Methods Used We measured ankle and brachial blood pressures (BP) on participants of the Jackson Heart Study during the first cycle between 2000 and 2004. Right and left ABI were defined as the ratio of the mean right arm BP to the mean right leg BP and the ratio of the mean left arm BP to the mean left leg BP respectively. The lower of the right and left ABI was used in this analysis. PAD was defined as an ABI <0.9. We performed logistic regression to relate CRP to PAD adjusting for age, sex, body mass index (BMI), systolic blood pressure, diabetes, total/HDL cholesterol, smoking and antihypertensive therapy. #### Summary of Results The study cohort consisted of 4,442 participants (mean age 54 ± 13 years, 64% women). There were high rates of obesity (52.6%), diabetes (17.5%) and hypertension (61.7%). Among study participants, 6.6% met criteria for PAD. CRP was significantly related to PAD both in the age-sex adjusted model (*P* = 0.006) and multivariable adjusted model (*P* = 0.002). #### Conclusions In this study investigating the relation of CRP to PAD in a population-based cohort of middle-aged African Americans, we found that CRP was significantly related to PAD adjusting for traditional cardiovascular risk factors. ### 54 LOWER INCIDENCE OF MYOCARDIAL INFARCTION AND STROKE IN THE METABOLIC SYNDROME IN A HISPANIC POPULATION P.I. Altieri, Y. Figueroa, N. Escobales, M. Crespo, H.L. Banchs *University of Puerto Rico, Medical Sciences Campus, San Juan, PR.* #### Purpose of Study One hundred and Sixty nine patients (P) with the metabolic syndrome (M.S.) were studied. #### Methods Used One hundred and Sixty nine patients (P) with the metabolic syndrome (M.S.) were studied. #### Summary of Results The mean age was 60 years. Fifty five percent were males and Forty five percent females. The mean body mass index was 30 kg/m2. The mean fasting blood sugar was 165 mg/dl. Ninety seven percent were diabetics Type II and three percent were diabetics Type I. The studied population showed a higher incidence of atrial fibrillation, when compared with a control group of diabetics (12 percent vs. 5.9% *P* < 0.001. The Metabolic group showed a subnormal ejection fraction (49 ± 4%) *P* <.0001 when compared with a control group (62 ± 12%) *P* < 0.001. The lipid profile of the metabolic syndrome was normal and none showed myocardial infarction or stroke. #### Conclusions In conclusion: this data shows that the Hispanic group with M.S. had no overt atherosclerotic disease, probably due to the normal lipid pattern seen in this group. This will produce a reduction of myocardial infarction and stroke in this group of P. ### 55 LONG TERM OUTCOMES OF PATIENTS RECEIVING DRUG ELUTING STENTS VS. BARE METAL STENTS D. Bansal1,2, S. Aleti1,2, R. Sukhija1,2, M. Marashdeh1,2, J. Mehta1,2, R. Sachdeva1,2 * 1Central Arkansas Veterans Healthcare Administration, Little Rock, AR and 2University of Arkansas for Medical Sciences, Little Rock, AR.* #### Purpose of Study There is growing concern about late stent thrombosis, associated myocardial infarction and mortality with drug eluting stents (DES). The objective of the study was to determine the long term outcome of DES in real world setting and its comparison with bare metal stents (BMS). #### Methods Used Study cohort was formed by all patients who had percutaneous intervention (PCI) done during January 2003 to August 2004 at one institution. Data were obtained regarding cardiac risk factors, medications at discharge, angiographic details and outcomes including death, target lesion revascularization (TLR), stent thrombosis and major adverse cardiac event (MACE). #### Summary of Results A total of 461 interventions using stents were done in patients who were followed up for a mean duration of 50 ± 8 months. Cardiac risk factors and medications at discharge were similar in patients with DES and BMS. There were more smokers in the DES group. Vessels implanted with DES had a smaller mean diameter compared to BMS (2.9 mm vs. 3.2, *P* = 0.001) and had longer lesion length (mean - 19 mm vs. 15 mm, *P* = 0.001). The long term outcomes were similar between the two groups (Table 1). View this table: [Table8](/content/57/1/301/T8) Long term outcome in DES and BMS groups of patients #### Conclusions Over the follow up period, DES had similar rates of death, TLR, stent thrombosis, and MACE (compared with BMS) despite smaller lumen diameter and longer lesion length. ### 56 EFFECT OF RENAL DISEASE ON SURVIVAL IN PATIENTS WITH IMPLANTABLE CARDIOVERTER DEFIBRILLATORS J. Bissett1,2, Z. Matin1, M. Leonardi1,2, R. Sachdev1,2 * 1University of Arkansas for Medical Sciences, Little Rock, AR and 2Central Arkansas Veterans Healthcare System, Little Rock, AR.* #### Purpose of Study The purpose of this study was to compare the survival rate of the patients with varying degrees of renal disease in patients with Implantable cardioverter defibrillators (ICD). #### Methods Used The data were obtained from a web based ICD database and a computerized medical record system for consecutive three hundred patients (n = 300), who had their ICD implantation at least three years before from the date of the statistical analysis were included in this study. These patients were grouped into three different groups, depending on their glomerular filtration rate (GFR, ml/min/1.73m2), obtained before the implantation of the Implantable cardioverter defibrillator ICD, i.e., normal stage, NRF or stage 1, GFR ≥ 60 or above; moderate CKD or, stage 2, or GFR30-59, and severe CKD stage, or stage 3, GFR<30. #### Summary of Results (1) Survival for 124 patients with GFR ≥ 60 ml/min/1.73 m2 was 98/124 (79.0%) with mean follow up of 1225.5 ± 390.4 days (2) Survival for 141 patients with GFR 30-59 ml/min/1.73 m2 was 91/141 (64.5%) with mean follow up of 1080.7 ± 481.9 days. (3) Survival for 35 patients with GFR <30 ml/min/1.73m2 was 11/35 (31.4%) with mean follow up of 719.0 ± 527.2 days. The p value for comparison of each group with all other groups was, *P* < 0.01. Survival rate compared between BiV pacing versus NonBiV pacing did not improve survival in any of three groups divided according to their GFR. Normal stage, NRF or stage 1, GFR ≥60 or above; (5/17, 29.4% vs. 21/107, 19.6%, *P* = 0.27); moderate CKD or, stage 2, BiV vs. NonBiV (9/20, 45.0% vs. 41/121, 33.8%, *P* = 0.33); or stage 3, GFR<30, BiV vs. NonBiV (5/8, 62.5% vs. 19/27, 70.3%, *P* = 0.69). #### Conclusions (1) GFR remains a strong predictor of survival in patients with Implantable cardioverter defibrillators (ICD). (2) BiV pacing in patients with congestive heart failure (CHF) with chronic renal disease does not improve survival to the level of the patients without BiV pacing. (3) Further study is required to identify the treatable factors that could improve survival. ### 57 ASSOCIATION OF BIRTH WEIGHT WITH HEART RATE, SYSTOLIC BLOOD PRESSURE AND THEIR PRODUCT BY GROWTH PERIODS: THE BOGALUSA HEART STUDY W. Chen, S.R. Srinivasan, G.S. Berenson *Tulane University, New Orleans, LA.* #### Purpose of Study This study examines the association of birth weight with heart rate, systolic blood pressure (SBP) and double (pressure-heart rate) product in black and white children, adolescents and young adults. #### Methods Used The study cohort included 8099 black (39.7%) and white children (n = 2870, age = 5-11 years), adolescents (n = 2629, age = 12-17 years) and adults (n = 2600, age = 18-48 years) enrolled in the Bogalusa Heart Study. Birth weight and gestational age information were obtained from Louisiana birth certificates. #### Summary of Results Blacks showed significantly higher SBP, but lower birth weight and heart rate than whites in children, adolescents and adults. In multivariate regression analyses, adjusting for sex, age, body mass index, gestational age and race, low birth weight was associated with faster heart rate in the total sample of adolescents (regression coefficient, β = -1.1 beat/kg, *P* < 0.001), with blacks and white having the same trends. Low birth weight was significantly and consistently associated with elevated SBP in all three growth periods in both blacks and whites (β = -0.9 to -2.2 mmHg/kg, *P* = 0.031 to <0.0001). Low birth weight was associated with higher double product in children (β = -77.4, *P* = 0.075), adolescents (β = -249.6, *P* < 0.0001) and adults (β = -219.8, *P* < 0.0001) in the combined sample of blacks and whites, with the same trends being noted in both races. #### Conclusions These findings suggest the sympathetic-parasympathetic balance, although not measured in this study, plays a critical role the association between fetal growth retardation and hemodynamic characteristics. ### 58 BLOOD PRESSURE VARIABILITY DURING CHILDHOOD IS ASSOCIATED WITH ADULTHOOD HYPERTENSION IN BLACKS AND WHITES: THE BOGALUSA HEART STUDY W. Chen, S.R. Srinivasan, L. Ruan, G.S. Berenson *Tulane University, New Orleans, LA.* #### Purpose of Study Increased blood pressure (BP) variability is associated with severity of end-organ damage and a higher rate of cardiovascular events. This study tested the hypothesis that childhood BP variability is associated with adulthood hypertension in adulthood. #### Methods Used The longitudinal study cohort consisted of 1797 adults (1091 whites and 706 blacks; 44.4% males; age = 21-48 years,) enrolled in the Bogalusa Heart Study. Subjects were examined serially 4-8 times for BP during childhood (age range = 4-19 years; mean age = 13.1 years), with 9035 measurements of BP. Quadratic curves of childhood BP versus age were constructed. The childhood BP variability was measured as rate of change (variability I), residuals from age-predicted values (variability II) and residuals from the overall mean values (variability III). #### Summary of Results The overall prevalence of hypertension in adulthood was 14.1% (n = 253), with blacks having a higher prevalence than whites (19.6% vs 10.5%, *P* < 0.001). Blacks also showed significantly greater childhood BP variability I and III than whites for systolic BP. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression analyses, using adulthood hypertension status as a dependent variable, adjusting for covariates. As shown in the table below, hypertension in adulthood was significantly associated with measures of BP variability during childhood except for systolic BP variability II. Further, the childhood BP variability was a stronger predictor of adulthood hypertension than childhood BP levels, although the levels were also significantly associated with adulthood hypertension. #### Conclusions These findings by showing a stronger association between childhood BP variability and adulthood hypertension suggest that the response of BP to environmental factors during growth may play an important role in the development of hypertension. View this table: [Table9](/content/57/1/301/T9) Odds ratio of childhood BP variability measures for adulthood hypertension, adjusting for race, sex, adulthood age and BMI, childhood mean BP levels and BMI variability (* p<0.001) ### 59 LONGER ADULTHOOD LEUKOCYTE TELOMERE LENGTH IS ASSOCIATED WITH HIGHER HIGH-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS MEASURED FROM CHILDHOOD TO ADULTHOOD: THE BOGALUSA HEART STUDY W. Chen1, J.P. Gardner2, M. Kimura2, X. Cao2, A. Aviv2, G.S. Berenson1 * 1Tulane University, New Orleans, LA and 2University of Medicine and Dentistry of New Jersey, Newark, NJ.* #### Purpose of Study Diminished levels of high-density lipoprotein cholesterol (HDL-C) are associated with an increased risk for atherosclerosis. Shortened leukocyte telomere length (LTL) also entails an increased atherosclerotic risk. This study assessed the hypothesis that HDL-C levels have an impact on LTL, an indicator of human biological aging. #### Methods Used The longitudinal study cohort consisted of 472 whites and 190 blacks enrolled in the Bogalusa Heart Study. Subjects were examined serially 3-12 times for HDL-C over an average of 26 years from childhood (mean age = 10.2 years, range = 4-17 years) to adulthood (mean age = 36.1 years, range = 18-43 years), with 3,893 serial observations. Telomere length was measured twice during adulthood at baseline (mean age = 31.5 years, range = 20-43 years) and follow-up (mean age = 37.7 years, range = 26-48 years). Growth curves of HDL-C were calculated; the area under the curve (AUC) was used as a measure of long-term levels from childhood to adulthood. #### Summary of Results Blacks displayed longer LTLs than whites at both baseline (7835 vs 7297 bp, *P* < 0.0001) and follow-up (7587 vs 7087 bp, *P* < 0.0001), and a faster yearly rate of shortening in LTL (42.1 vs 34.1 bp, *P* = 0.030). Multivariate regression analyses, using LTL measured at follow-up in adulthood as a dependent variable, showed that LTL was positively associated with HDL-C in childhood (regression coefficient (bp per mg/dL) β = 3.1, *P* = 0.024), adulthood (β = 4.4, *P* = 0.058) and AUC from childhood to adulthood (β = 12.2, *P* = 0.0004) in the combined sample of blacks and whites, adjusting for race, sex, age, body mass index and current smoking status. The association between LTL and HDL-C AUC was stronger in females (β = 18.5, *P* < 0.001) than in males (β = 2.9, *P* = 0.590) (difference in slopes *P* = 0.037). Further, a slower rate of LTL shortening per year was significantly associated with higher HDL-C AUC in the total sample (*P* = 0.033), adjusting for baseline LTL and the above covariates. #### Conclusions These findings suggest that the association between HDL-C and LTL might be explained by the lifelong status of oxidative stress and inflammation. ### 60 DID HURRICANE KATRINA AFFECT THE INCIDENCE OF ACUTE CORONARY SYNDROMES IN NEW ORLEANS? S. Gautam, J. Menachem, S. Srivastav, P. Delafontaine, A. Irimpen *Tulane University School of Medicine, New Orleans, LA.* #### Purpose of Study In August 2005, New Orleans was hit by Hurricane Katrina, the biggest natural disaster in the United States. Previous studies have shown an increase in acute myocardial infarction (AMI) in the immediate hours to weeks after natural disasters. The goals of our study were to detect any long-term increase in the incidence of AMI after Katrina and to investigate any pertinent contributing factors. #### Methods Used This was a single center retrospective cohort observational study. Patients admitted with AMI to Tulane University Hospital, in the two years before Katrina and in the two years after the hospital reopened (5 months after Katrina) were identified from hospital records. The two groups (pre- and post- Katrina) were compared for pre-specified demographic and clinical data. #### Summary of Results In the post-Katrina group, there were 246 admissions for AMI, out of a total census of 11,282 patients (2.18%), as compared to 150 AMI admissions out of a total 21,229 patients (0.71%) in the pre-Katrina group (*P* < 0.0001). The post-Katrina group had significantly higher prevalence of unemployment (*P* = 0.0003), lack of medical insurance (*P* < 0.0001), medication noncompliance (*P* = 0.0001), smoking (*P* = 0.001), substance abuse (*P* = 0.03), first-time hospitalization (*P* < 0.001), local residents rather than visitors (*P* < 0.0001), and people living in temporary housing (*P* = 0.003). There was no significant difference in the racial distribution in the two groups. #### Conclusions The role of chronic stress in pathogenesis of AMI is poorly understood, especially in the aftermath of natural disasters. Our data suggests that Katrina led to prolonged loss of employment and insurance, decreased access to preventive health services and an increased incidence of AMI. In addition, it appears that chronic stress after a natural disaster can foster tobacco abuse and medication and therapeutic noncompliance. We found a three-fold increased incidence of AMI more than two years after Hurricane Katrina. Even allowing for the loss of some local hospitals after the disaster, this represents a significant change in overall population health, and supports the need for further study into the health effects of chronic stress. ### 61 ANOREXIA NERVOSA, EXTREME EXERCISE AND ABNORMAL CARDIAC INDICES M.A. Grenier, J.T. Bricker, C.M. Cottrill *University of Kentucky, Lexington, KY.* #### Purpose of Study Anorexia nervosa (AN) is associated with extreme bradycardia and echocardiographic findings including left ventricular hypertrophy (LVH), mitral valve prolapse, infectious endocarditis, pericardial effusion (PCE) and poor function. Extreme athletes (EA) develop "athletic heart", which consists of LV dilation and hypertrophy. AN patients who exercise to the extreme, are subject to the combined stressors of each state, and may develop findings of each. We describe 3 girls with AN and EA, with associated cardiac findings which subsequently reversed with weight gain and rest. #### Methods Used This is a retrospective chart review. All patients were followed in an outpatient setting, re-fed slowly, and were asked to refrain from extreme exercise. Serial EKGs and echocardiograms were obtained as patients regained weight. #### Summary of Results See Table 1. All 3 patients exercised to the extreme, and lost 1/3 of their initial body weight. They all manifested bradycardia and diminished global LV systolic function with the weight loss and exercise. Two out of three had LV dilation, but none had LVH. With ∼5 kg weight gain, all had return of normal LV systolic function. One persisted with increased LV dimension even when function returned to normal; this patient also manifested ectopy. #### Conclusions Extremes in body mass indices have a myriad of effects on the cardiovascular system, which appear to resolve as patients' BMI move toward normative. Additionally, EA is associated with increased LVED and LVH. These girls did not manifest LVH, and may not have been able to mount a normal response. Patients with extremes in weight should be followed prospectively with sensitive echocardiographic parameters to supplement counseling regarding further weight gain and loss. The molecular cascades and neurohormones involved in these diseases should be studied. View this table: [Table10](/content/57/1/301/T10) Degree of Weight Loss, Exercise and Cardiac Findings ### 62 Left Ventricular Chamber Size In Patients With Diastolic Heart Failure E.B. Hanna, D.L. Glancy, F. Helmcke *LSU, New Orleans, LA.* #### Purpose of Study To evaluate the left ventricular (LV) diastolic chamber size in patients with heart failure and normal ejection fraction (HFNEF). #### Methods Used We reviewed the coded database of echocardiographic studies performed at one institution between July of 2007 and June of 2008. We performed a retrospective descriptive study of 35 patients who had a normal ejection fraction (>55%) and elevated left-sided filling pressures at the time of the echocardiogram, according to the echocardiographic parameters of advanced diastolic dysfunction. We looked at their left ventricular internal diastolic diameter (LVIDD). #### Summary of Results Our population had a high prevalence of hypertension (100%), obesity (63%), diabetes (40%), chronic kidney disease stages 3 to 5 (51%), coronary artery disease (25%), and anemia (43%). The left atrial antero-posterior diameter was increased (>3.9 cm) in 86% of the patients, and left ventricular hypertrophy (defined as interventricular septal thickness >11 mm) was identified in 65% of the patients. Only 14% of the patients had an increased left ventricular internal diastolic diameter above the absolute upper limits of normal (>5.9 cm for males, >5.3 cm for females). However, the distribution of left ventricular end-diastolic diameter values was mildly skewed to higher values in comparison to a normal historical population: 4.85 + /- 0.5 cm for females, 5.3 + /- 0.5 cm for males, as compared to 4.6 + /- 0.3 cm for normal females (p 0.045) and 5 + /- 0.4 cm for normal males (*P* < 0.001).The distribution of indexed LVIDD was, however, comparable to that of a normal historical population: 2.6 + /- 0.4 cm/m2, as compared to 2.7 + /- 0.2 cm/m2 for the normal population (p NS) #### Conclusions In a population of patients with a normal ejection fraction, high left ventricular filling pressures, and a high prevalence of comorbid conditions, LV diastolic size is only mildly increased in comparison to a normal population and is rarely increased above the absolute upper limit of normal. This confirms the concept that HFNEF is related to an abnormal diastolic left ventricular pressure-volume relationship, with no or with mild ventricular volume overload. ### 63 INSULIN-LIKE GROWTH FACTOR-1 REGULATES GLUTATHIONE PEROXIDASE EXPRESSION AND ACTIVITY IN VASCULAR ENDOTHELIAL CELLS Y. Higashi, A.K. Pandey, P. Delafontaine *Tulane University School of Medicine, New Orleans, LA.* #### Purpose of Study Oxidative stress plays an important permissive role in the genesis of multiple inflammatory diseases, including atherosclerosis. We have shown recently that systemic administration of insulin-like growth factor-1 (IGF-1) in apoE null mice prevents progression of atherosclerosis, possibly via an anti-inflammatory and anti-oxidant effect. In human vascular endothelial cells IGF-1 regulates activity of glutathione peroxidase (GPX), which is a crucial anti-oxidant enzyme and hence is atheroprotective. The aim of this study was to characterize mechanisms whereby IGF-1 regulates GPX expression in endothelial cells. #### Methods Used Cultured human aortic endothelial cells (ECs) were treated with human recombinant IGF-1 (0-100 ng/mL) and tested for oxidized low-density lipoprotein (oxLDL) induced reactive oxygen species (ROS) generation. GPX gene and protein expression levels were tested by realtime-PCR analysis and Western blot analsys. #### Summary of Results IGF-1 prevented oxLDL induced ROS generation (67 ± 9% decrease with 100 ng/mL IGF-1 vs. oxLDL alone at 24 hr, *P* < 0.01) as assessed by 5-carboxy-2',7'-dichlorodihydrofluorescein diacetate staining. IGF-1 did not alter superoxide dismutase or catalase activity but markedly increased glutathione peroxidase activity, which was apparent at 6 hr, persisted up to 24 hr (control 24 hr, 4.4 ± 1.2 U/mg protein; IGF-1 24 hr, 21.2 ± 2.1 U/mg protein, *P* < 0.01). IGF-1 (100 ng/mL) increased GPX-1 protein levels by 2.6-fold at 24 hr (*P* < 0.01), however IGF-1 did not increase GPX-1 mRNA levels, indicating translational or post-translational regulation. To identify the signaling pathway mediating IGF-1 upregulation of GPX-1 we exposed ECs to IGF-1 in the presence or absence of ERK1/2 (PD98059, 25 μM), p38 MAPK (SB202190, 10 μM), and PI3K (LY294002, 50 μM) inhibitors. LY294002 blocked IGF-1 induced GPX upregulation, indicating involvement of the PI3K pathway. #### Conclusions IGF-1 exerts potent anti-oxidant effects on EC, mediated by translational/post-translational increases in GPX expression and activity via a PI3K dependent pathway. ### 64 ECHOCARDIOGRAPHY REVEALS PROGRESSIVE CARDIAC DYSFUNCTION IN MG-DEFICIENT RATS J.H. Kramer1, C. Spurney3, I. Mak1, M. Iantorno3, C. Tziros2, W.B. Weglicki1,2 * 1The George Washington University Medical Center, Washington, D.C., DC; 2The George Washington University Medical Center, Washington, D.C., DC and 3Children's National Medical Center, Washington, D.C., DC*. #### Purpose of Study The impact of chronic dietary Mg-deficiency on in situ cardiac function in rats was investigated using non-invasive echocardiography (EC). #### Methods Used Male Sprague-Dawley (180 g) rats were placed on Mg-deficient (MgD, 9% RDA) or Mg-sufficient (MgS, 100% RDA) diets for 3 or 5 weeks. EC was performed at 3 and 5 wks, and blood samples collected for assessment of substance P (SP by ELISA), and oxidative stress indices (RBC glutathione loss, isoprostane production and neutrophil basal superoxide production). #### Summary of Results Three wks of MgD failed to induce significant changes in EC parameters (vs MgS), except for a 20% decline (*P* < 0.05) in the mitral valve E/A ratio (E/A), a sign of early diastolic dysfunction. By contrast, 5 wks of MgD led to significant (*P* < 0.05) depression in: LV systolic function (LV ejection fraction [LVEF] by 6.1%; % fractional shortening [%FS] by 16.5%; and maximum aortic pressure [Pmax] by 18.9%); diastolic function [E/A] by 27.7%; and interventricular septum diameter in systole [IVSs] by 18.6%. The cardiac dysfunction at 5 wks was preceded by elevations at 3 wks (and observed at 5 wks) in circulating SP levels (6.5-7.2 fold), RBC glutathione loss (40-45%), plasma isoprostane elevations (50-100%), and higher neutrophil basal superoxide generation (3-5 fold) vs MgS. #### Conclusions The progressive development of oxidative injury during chronic MgD involves neurogenic inflammation due to SP (Exp. Biol. Med. 228:665, 2003). To our knowledge, this is the first echocardiographic demonstration of cardiac dysfunction in an animal model of MgD. Supported by NIH RO1 HL-62282 & HL-65178. ### 65 ALL-TRANS RETINOIC ACID ENHANCES TRANSCRIPTIONAL ACTIVITY AND EXPRESSION OF GUANYLYL CYCLASE/NATRIURETIC PEPTIDE RECEPTOR-A IN VASCULAR SMOOTH MUSCLE CELLS P. Kumar, K.N. Pandey, *Tulane University Health Sciences Center and School of Medicine, New Orleans, LA.* #### Purpose of Study Cardiac hormone atrial natriuretic peptide (ANP) plays a pivotal role in maintaining cardiovascular homeostasis and preventing cardiac remodeling. The binding of ANP to guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) produces second messenger cGMP, which activates downstream signaling and biological effects of ANP/NPRA including vasorelaxation, antimitogenic, and cardiac anti-hypertrophic effects. The present study was aimed at gaining insight into the function of all-trans retinoic acid (ATRA) involving transcription factor Ets-1 in the regulation of Npr1 (coding for GC-A/NPRA) gene transcription and expression, which is an important regulator of ANP-dependent signaling in pathophysiology of hypertension and cardiovascular disorders. #### Methods Used Npr1 gene promoter- reporter deletion constructs were transiently transfected in cultured rat thoracic aortic smooth muscle cells (RTASMCs) using Lipofectamine-2000 and transcriptional activity was measured by dual luciferase assay. To determine the effect of all-trans retinoic acid (ATRA) signaling on NPRA expression, electrophoretic mobility shift assay, RT-PCR, and cGMP assays were performed. #### Summary of Results Promoter deletion analysis and luciferase assays demonstrated that ATRA enhances Npr1 promoter activity by more than 6- fold in a dose-dependent manner and induced NPRA mRNA levels by 4-fold in a time-dependent manner. The effect of ATRA is mimicked by TTNPB, a RA receptor agonist, which increased Npr1 gene transcription. ATRA also increased Ets-1 expression and enhanced its in vitro binding to Npr1 promoter as confirmed by gel shift assay. ATRA enhanced NPRA protein expression, its guanylyl cyclase activity, and ANP-dependent intracellular accumulation of second messenger cGMP. #### Conclusions The results demonstrate that retinoic acid signaling enhances Npr1 gene transcription and expression. The identification of retinoid signaling as a regulator of Npr1 gene transcription and protein expression will have important implications in cardiovascular regulation and prevention of cardiac hypertrophy and remodeling. ### 66 METABOLIC INTERVENTION IMPROVES MECHANICAL FUNCTION AND ATTENUATES ATP DEPLETION IN EX-VIVO STORED RAT HEARTS A. Markov, W.S. Bennett, T.N. Skelton *Univ. of Mississippi Medical Center, Jackson, MS.* #### Purpose of Study The high-energy intermediate of glycolysis Fructose-1,6-Diphosphate (FDP) is reported to provide significant protection during ischemia and following reperfusion of ischemic organs and tissues. Based on these observations, we investigated if FDP would provide similar protection to ex-vivo stored hearts. #### Methods Used Prior to harvesting the hearts from anesthetized rats (n = 42) 19 received IV bolus of FDP (450 mg/kg; 10%) and the rest (n = 23) the same amount of glucose. The hearts were removed, and aorta and left atrium were attached to modified Langerdorf apparatus and perfused with Krebs-Henseleit (n = 23) and 19 with same perfusate containing 0.07 mg/ml of FDP for 15 min (37°C). Then the control hearts (n = 23) were flushed with cardioplegic solution (Isolite, K + 20 mEg/L) and the rest with the same solution containing 1 mg/ml of FDP. They were respectively placed in saline or saline containing 1 mg/ml of FDP and stored for 4 hrs. at 4°C. #### Summary of Results Pre-storage HR, AoP, CBF and cardiac output (CO) were no different between the groups. However, at 1 hr and 30 min post storage, all FDP treated hearts (n = 10) were working and only 4 of the 14 controls. (*P* < 0.05). Post-storage HR, CO, aortic systolic and mean pressures were significantly higher in the FDP group (*P* < 0.05, *P* < 0.02, *P* < 0.01, and *P* < 0.01, respectively). The myocardial ATP content at 15 min post storage reperfusion in the FDP group (n = 9) was higher than in the saline group (n = 9) (*P* < 0.01). Myocardial wet/dry tissue ratio of these hearts was lower in the FDP group (*P* < 0.01). #### Conclusions FDP significantly improved the mechanical function, attenuated ATP depletion and reduced tissue water accumulation in ex-vivo stored rat hearts during the post ischemic storage reperfusion period. ### 67 A COMPARATIVE ANALYSIS OF THE IMPACT OF MULTIPLE CARDIOVASCULAR RISK FACTORS ON THE FEMORAL AND CAROTID ARTERY INTIMA-MEDIA THICKNESS IN ASYMPTOMATIC YOUNG ADULTS: THE BOGALUSA HEART STUDY T. Paul, W. Chen, S. Srinivasan, J. Rice, A. Toprak, J. He, G. Berenson *Tulane University, New Orleans, LA*. #### Purpose of Study Information on the impact of multiple cardiovascular (CV) risk factors on the intima-media thickness (IMT) of femoral and carotid artery segments measured simultaneously has not been studied in younger adult population. #### Methods Used Femoral and carotid IMT were measured by B-mode ultrasonography in 1080 black and white subjects (aged 24-43 years; 71% white, 43% male) of the Bogalusa Heart Study. #### Summary of Results Femoral IMT was correlated with common carotid IMT (r = 0.19, *P* = 0.001), carotid bulb IMT (r = 0.19, *P* = 0.001), internal carotid IMT (r = 0.09, *P* = 0.01), and composite carotid IMT (r = 0.09, *P* = 0.001). In multivariate analyses, systolic blood pressure (SBP), age, male gender, black race, total cholesterol to HDL cholesterol ratio (total/HDL), waist circumference, cigarette smoking and LDL cholesterol were entered as predictor variables in that order for the common carotid IMT (R2 = 0.28); age, total/HDL, SBP, cigarette smoking, male gender and BMI for the carotid bulb IMT (R2 = 0.18); SBP, age, total/HDL, and male gender for the internal carotid IMT (R2 = 0.10); SBP, age, total/HDL, male gender, black race, cigarette smoking and LDL cholesterol for the composite carotid IMT (R2 = 0.27); SBP, age, male gender, cigarette smoking and total/HDL for the femoral IMT (R2 = 0.11). Mean IMT increased with increasing number of risk factors in all arterial segments; p for trend = 0.003 for femoral artery and p for trend = 0.001 for all carotid segments. Associated with 0, 1-2, 3 and 4-5 risk factors, the respective mean IMT (mm) values were 0.72, 0.75, 0.80, 0.84 for common carotid; 0.91, 0.96, 1.05, 1.08 for carotid bulb; 0.69, 0.72, 0.75, 0.79 for internal carotid; 0.72, 0.75, 0.81, 0.85 for composite carotid and 0.66, 0.69, 0.73, 0.79 for the femoral. #### Conclusions Although the femoral IMT and different segments of carotid IMT are significantly inter-correlated, the weak strength of association implies that in low risk population the values of femoral and carotid IMT are not interchangeable. The observed deleterious effect of CV risk factors on IMT of the femoral and carotid arterial segments provides evidence of silent systemic atherosclerosis in young adults. ### 68 ISCHEMIA-INDUCED REDUCTIONS IN ACTIVITY OF PROTEIN PHOSPHATASE 2A AS AN ENDOGENOUS CARDIOPROTECTIVE MECHANISM T.A. Pegram1, P. Hofmann2 * 1University of Tennessee Health Science Center, Memphis, TN and 2University of Tennessee Health Science Center, Memphis, TN.* #### Purpose of Study We hypothesized that myocardial ischemia causes a decrease in activity of protein phosphatase 2a (PP2a) which increases the phosphorylation of phospholamban (PLB), a protein important for cellular Ca2 + homeostasis, myocardial function, and health. #### Methods Used To show that myocardial ischemia resulted in an decrease in activity of PP2a and an increase in phosphorylation of PLB, we subjected isolated hearts to ischemia and varying periods of reperfusion, and determined PP2a activity and the phosphorylation state of the PP2a target protein PLB. Ischemia reduced PP2a activity by 40% and significantly increased the phosphorylation of PLB in the heart. To establish that a decrease in PP2a, independent of kinases, alters phosphorylation and initiates a beneficial effect, we selectively reduced PP2a activity prior to stressing the hearts. To do this we exposed adult rat hearts to concentrations of okadaic acid (OKA) or S-adenosyl-homocysteine (SAH) to demethylate the catalytic subunit of PP2a (PP2aC) and decrease PP2a activity. #### Summary of Results Pre-exposure with both OKA and SAH significantly reduced the methylation state of PP2a prior to induced ischemia and lead to increased percent functional recoveries in post-ischemic hearts. These results are consistent with the idea that ischemia-induced reductions in PP2a activity through reversible demethylation is an endogenous protective mechanism in the heart. #### Conclusions Treatment with drugs that reduce the activity of PP2a through demethylation may be clinically useful to improve cardiac outcomes if given prior to transient ischemia due to bypass surgery or chemotherapy. ### 69 PREVENTION OF MUSCLE WASTING IN RATS WITH ALDOSTERONISM: RESPONSE TO ZINC SUPPLEMENT AND INSULIN GROWTH FACTOR-1 W.J. Reed, Y. Sun, D.B. Thomason, S.K. Bhattacharya, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN.* #### Purpose of Study Chronic activation of the renin-angiotensin-aldosterone system (RAAS) is accompanied by a progressive loss of soft tissue. To examine pathophysiologic responses involved in muscle wasting, we employ a model of aldosteronism in rats, where a failure to gain weight is seen, together with skeletal muscle atrophy. In this context, aldosterone/salt treatment (ALDOST) is associated with increased excretory losses of Zn and a consequent hypozincemia, together with a downregulation of Zn-dependent insulin growth factor (IGF)-1, a mediator of the growth promoting properties of growth hormone. We hypothesized a Zn supplement or IGF-1 given alone or in combination would prevent the failure to gain weight and skeletal muscle atrophy. #### Methods Used Uninephrectomized 8-week-old male Sprague-Dawley rats received ALDO by implanted minipump (0.75 μg/h) for 4 wks, together with 1% NaCl/0.4% KCl in drinking water. A subgroup of these rats were given a ZnSO4 supplement (dietary, 40 mg/day) or IGF-1 (1.5 mg/kg/day by minipump) alone or in combination. Age-/gender-matched rats served as controls. Four wks later, we monitored body weight and skeletal muscle (gastrocnemius) weight. #### Summary of Results Body weight at 12 wks of age in control rats (290 ± 4 g) was not attained in rats receiving 4 wks ALDOST (234 ± 10 g; *P* < 0.05) and this failure to gain weight was not prevented by cotreatment with either ZnSO4 supplement (247 ± 6 g) or IGF-1 (256 ± 8 g) alone or ZnSO4 plus IGF-1 (208 ± 8 g). A wasting of skeletal muscle was seen with 4 wks ALDOST compared to controls (0.50 ± 0.02 vs. 0.60 ± 0.02 g; *P* < 0.05). Cotreatment with ZnSO4 (0.51 ± 0.02 g) or IGF-1 (0.44 ± 0.02 g) alone or ZnSO4 plus IGF 1 (0.44 ± 0.02 g) did not prevent muscle wasting. #### Conclusions In growing rats receiving 4 wks ALDOST, a failure to gain weight and skeletal muscle wasting is found and is not prevented by cotreatment with ZnSO4 supplement or IGF-1 given alone or in combination. These findings suggest that unless aldosteronism is corrected, other strategies will not prevent muscle wasting. ### 70 HOMOCYSTEINE IS ADVERSELY ASSOCIATED WITH ARTERIAL STIFFNESS IN BLACK AND WHITE YOUNG ADULTS: THE BOGALUSA HEART STUDY L. Ruan1,2, W. Chen1, S.R. Srinivasan1, J. Xu1, A. Toprak1, G.S. Berenson1 * 1Department of Epidemiology, New Orleans, LA and 2Xi'an, China.* #### Purpose of Study That elevated of plasma homocysteine is adversely associated with atherothrombosis is well recognized. However, findings on the association between homocysteine and arterial wall stiffness, an indicator of vascular damage, are conflicting. The aim of this study was to determine the association between the homocysteine and arterial wall stiffness in a biracial (black-white) community-based cohort of asymptomatic young adults. #### Methods Used Plasma homocysteine along with other cardiovascular disease risk factor variables were measured in 735 white and 294 black subjects, aged 24-44 years, enrolled in the Bogalusa Heart Study. Large artery stiffness was assessed in terms of aorta-femoral pulse wave velocity (af-PWV) by echo-Doppler. #### Summary of Results Males vs females showed higher fasting homocysteine levels (8.85 vs 7.32 µmol/L, *P* < 0.01); blacks vs whites had higher af-PWV (5.47 vs 5.24 m/sec, *P* < 0.01). In bivariate analyses, log-transformed homocysteine was significantly correlated with af-PWV (r = 0.111, *P* = 0.0004). In multivariate stepwise regression analyses, systolic blood pressure (regression coefficient β = 0.022, *P* < 0.0001, R2 = 0.167), age (β = 0.041, *P* < 0.0001, R2 = 0.037), heart rate (β = 0.011, *P* = 0.0001, R2 = 0.014), log-homocysteine (β = 0.262, *P* = 0.0005, R2 = 0.0097), log-HOMA-IR (β = 0.155, *P* < 0.0001, R2 = 0.009) and smoking (β = 0.189, *P* = 0.0015, R2 = 0.008), in that order, were independently and positively associated with af-PWV. Further, the mean value of af-PWV significantly increased with increasing quartiles of homocysteine specific for race, sex, age and smoking (p for linear trend = 0.038). #### Conclusions Plasma homocysteine is an independent correlate of arterial stiffness in asymptomatic black and white young adults, and may be a potential marker for cardiovascular disease risk in this age group. ### 71 FETAL FOTOS L.E. Sauley1, J. Grabham1, W.N. O'Connor2, C.M. Cottrill1 * 1University of Kentucky, Lexington, KY and 2University of Kentucky, Lexington, KY.* #### Purpose of Study Fetal ultrasounds with anatomic correlation #### Methods Used Clinical studies #### Summary of Results Case 1. At 20 weeks gestation a female fetus presented with poor left ventricular(LV) function. Progressive enlargement of the LV with the development of Endocardial Fibroelastosis(EFE) and eventual right ventricular enlargement ensued. Neonatal transplant was considered, but the family preferred compassionate care. The baby was born at term, weighing 3.32 kg. The baby survived for 24 hours and died peacefully. Autopsy confirmed severe enlargement of the LV with thinning of the musculature and marked EFE. Serial sectioning of the left main coronary artery revealed occlusion with total fibrosis of the left anterior descending artery and the circumflex artery was very hypoplastic. The fetal echocardiogram and autopsy photos are presented Case 2: At 22 weeks gestation a male fetus presented for cardiac ultrasound. The Aorta, the umbilical arteries and the coronary arteries were very bright, suggesting abnormal calcification. An intrauterine death occurred at 35 weeks and the baby was delivered the next day. At autopsy, the diagnosis of Idiopathic Arterial Calcification was made and slides of the ultrasound and microscopics of the arteries are presented. Case 3 The cardiac diagnosis of Double-Outlet Right ventricle was made in a female infant who also developed intrauterine growth retardation. Mother declined amniocentesis. The baby girl was born at 37 weeks gestation with features of trisomy 18 and died on the 6th day of life. Ultrasound and autopsy photos are included in the presentation. Case 4: A primagravida, 24 weeks pregnant with identical twins was referred for suspected cardiac abnormality in one twin. Severe Ebstein's anomaly was present with associated fetal hydrops. Over time, the hydrops became severe. As the baby sickened, ultrasounds of the twin revealed elevated heart rate and accelerated breathing rates. The twin with Ebstein's anomaly died at 30 weeks, and the surviving twin was delivered at 33 weeks without anomalies. The survivor was discharged after a 4 week neonatal ICU stay. #### Conclusions Even complex cardiac defects can be identified prenatally. ### 72 SKELETAL MUSCLE-SPECIFIC OVEREXPRESSION OF INSULIN-LIKE GROWTH FACTOR I DECREASES OXIDATIVE STRESS AND PREVENTS ANGIOTENSIN II-INDUCED SKELETAL MUSCLE WASTING: NOVEL POTENTIAL THERAPY TO TREAT CACHEXIA IN CONGESTIVE HEART FAILURE L. Semprun-Prieto1,2, S. Sukhanov1, T. Yoshida1, C. Vaughn1, P. Delafontaine1 * 1Tulane University, New Orleans, LA and 2Tulane University, New Orleans, LA.* #### Purpose of Study Congestive heart failure (CHF) is associated with elevated levels of angiotensin II (ANG) and skeletal muscle wasting (cachexia). We have shown that ANG infusion in FVB mice induces skeletal muscle wasting and increases oxidative stress. Since we also found that insulin-like growth factor I (IGF-1) exerts anti-oxidant effects in a murine model, we hypothesized that skeletal muscle-specific IGF-1 overexpression would decrease ANG-induced muscle wasting and/or oxidative stress. #### Methods Used Mice overexpressing IGF-1 under control of the skeletal muscle-specific type II myosin light chain promoter (MLC) and control mice (FVB) were infused with 1 ug/kg ANG or vehicle (SHM) for 7 d. Oxidative stress was assessed in muscle homogenates using superoxide-sensitive dye L-012. Gene expression was measured by RT-PCR. #### Summary of Results ANG decreased skeletal muscle weight in FVB (ANG/SHM, gastrocnemius: 99.8 ± 3.6/122.3 ± 4.2 mg; tibialis anterior: 32.0 ± 1.3/41.3 ± 1.3 mg; quadriceps: 117.6 ± 6.1/160.6 ± 6.7 mg), however no significant muscle wasting was found in ANG-infused MLC. ANG induced leftward shift in myofibers number/size distribution and decreased cross-sectional area (CSA) of type I and II myofibers in FVB (type I, 443 ± 22/528 ± 28 um2; type II, 620 ± 40/835 ± 44 um2) without effect on myofibers distribution and CSA in MLC as detected by immunostaining of gastrocnemius muscle with isoform-specific antibodies. ANG increased superoxides in FVB by 67% (228 ± 25 vs. 149 ± 21 RFU/mg protein, *P* < 0.005) but did not significantly increase superoxides in MLC (376 ± 99 vs. 298 ± 81 RFU/mg protein, *P* = NS). 250 uM Apocynin (a specific NADPH oxidase inhibitor) dramatically suppressed ANG-induced superoxides in muscle FVB (91 ± 5% decrease vs. control). ANG II also upregulated NOX4 (a NADPH oxidase subunit) gene expression in skeletal muscle and this effect was greater in FVB (3.6-fold increase, *P* < 0.05) compared to MLC (2.1-fold increase, *P* = NS). #### Conclusions Thus, IGF-1 overexpression suppresses oxidative stress and efficiently blocks skeletal muscle wasting, possibly via inhibition of NADPH oxidase dependent superoxide formation. ### 73 REVERSIBLE LYMPHOCYTOPENIA IN AFRICAN-AMERICANS WITH DECOMPENSATED BIVENTRICULAR FAILURE A.U. Shahbaz, S. Ali, M.D. Nelson, R.C. Davis, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN*. #### Purpose of Study A reduction in relative (%L) lymphocyte count has been found in Caucasians with splanchnic congestion of diverse causality, including constrictive pericardial disease or marked tricuspid regurgitation, and which is reversible following surgical intervention. Whether a lymphocytopenia occurs in African-American (AA) patients with decompensated biventricular failure having splanchnic congestion (DecompHF) due to a dilated cardiomyopathy (DCM) is unclear. Whether it would be reversible once the splanchnic congestion had been resolved by medical management is also uncertain. Accordingly, we monitored %L in AA patients hospitalized because of decompensated biventricular failure due to a DCM of ischemic or nonischemic origin and having reduced ejection fraction (<35%). We repeated the assessment of %L weeks later and after signs and symptoms of splanchnic congestion had resolved. #### Methods Used Fifty-six AA patients (42 males; 51.8 ± 1.7 yrs) hospitalized at the Regional Medical Center here in Memphis because of DecompHF and who on admission were found to have jugular venous distention, tricuspid regurgitation, hepatic and splanchnic congestion, and bilateral lower extremity edema, together with echocardiographic evidence of tricuspid regurgitation and dilated inferior vena cava without respiratory variation. Weeks later in the outpatient clinic, %L was again available in 31 of these patients (31 males; 51.8 ± 2.6 yrs), who now were compensated without splanchnic congestion. #### Summary of Results In AA patients hospitalized with DecompHF, %L was reduced (14.44 ± 0.95%) below the normal reference range (20-40%) on admission and this lymphocytopenia was present in both AA men and women and irrespective of the etiologic origin of their DCM. Follow-up %L had normalized (24.67 ± 1.02%) when these patients no longer had splanchnic congestion. #### Conclusions A relative lymphocytopenia is found on admission in AA patients hospitalized with DecompHF and which is reversible weeks after splanchnic congestion has resolved with medical therapy. These findings call into question the role of a reversible enteric loss of lymphocytes and/or an altered behavior of the gut-associated lymphoid tissue, the body's largest lymphoid organ. ### 74 SKELETAL MUSCLE WASTING IN RATS WITH ALDOSTERONISM. RESPONSE TO TREATMENT WITH ZINC AND INSULIN GROWTH FACTOR-1 J.N. Sherrod, Y. Sun, D.B. Thomason, S.K. Bhattacharya, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN.* #### Purpose of Study A chronic activation of the renin-angiotensin-aldosterone system contributes to a loss of skeletal muscle to eventuate in a wasting syndrome termed cardiac cachexia. In 8-wk-old young adult rats receiving chronic aldosterone/salt treatment (ALDOST), a failure to gain body weight is seen and includes skeletal muscle atrophy and bone resorption. Responsible mechanisms are under investigation. In this context, ALDOST is accompanied by increased urinary and fecal excretory losses of Zn leading to hypozincemia, together with skeletal muscle atrophy and a downregulation of Zn2 + -dependent insulin growth factor (IGF)-1, which mediates the growth-promoting actions of growth hormone. We hypothesized it possible to reverse muscle wasting seen at wk 4 of ALDOST by cotreating rats with either Zn alone or Zn plus IGF-1. #### Methods Used Eight-week-old male Sprague-Dawley rats received ALDO (0.75 μg/h by implanted minipump) together with 1% NaCl and 0.4% KCl in drinking water for 8 wks. At wk 4 of ALDOST, cotreatment was initiated and continued for 4 wks: a ZnSO4 supplement (dietary, 40 mg/day), which earlier studies indicated would prevent hypozincemia; or ZnSO4 plus IGF-1 (1.5 mg/kg/day by implanted minipump). At wk 8 we monitored: body weight and skeletal muscle (gastrocnemius) weight. Age-/gender-matched rats served as controls. #### Summary of Results As compared to controls, body weight at wk 8 ALDOST was reduced (381 ± 5 vs. 240 ± 16 g; *P* < 0.05). This failure to gain weight was not prevented by ZnSO4 supplement (228 ± 12 g) or ZnSO4 plus IGF-1 (234 ± 8 g). Skeletal muscle weight was reduced at wk 8 ALDOST compared to controls (0.41 ± 0.05 vs. 0.78 ± 0.02 g; *P* < 0.05) and this atrophy of muscle was not prevented by ZnSO4 supplement (0.38 ± 0.02 g) or ZnSO4 plus IGF-1 (0.40 ± 0.02 g). #### Conclusions Chronic aldosteronism in growing rats is accompanied by a failure to gain weight and skeletal muscle atrophy. The established muscle wasting seen at wk 4 ALDOST is not reversed by 4-wk treatment with a ZnSO4 supplement or ZnSO4 plus IGF-1 which suggests the need to reverse aldosteronism before a recovery in wasting can be expected. ### 75 THE ABSENCE OF HYPERGLYCEMIA ON ADMISSION IN NONDIABETIC PATIENTS HOSPITALIZED WITH OR WITHOUT DECOMPENSATED HEART FAILURE M.S. Shook, H. Zafarullah, M.D. Nelson, R.C. Davis, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN*. #### Purpose of Study Critically ill patients with multiorgan failure may develop stress-related hyperglycemia (>140 mg/dL) even in the absence of diabetes. Regimented insulin therapy has been suggested to maintain serum glucose between 80-110 mg/dL in intensive care unit patients. An activation of the hypothalamic-pituitary-adrenal axis with elevated serum cortisol and catecholamines occurs in patients with decompensated, biventricular heart failure having hepatic and splanchnic (which includes the pancreas) congestion (DecompHF) and could contribute to hyperglycemia. It is presently uncertain whether nondiabetic patients hospitalized with DecompHF would have hyperglycemia on admission. #### Methods Used We retrospectively examined admission serum glucose in 41 patients without a history of diabetes, who were hospitalized at our urban medical center with DecompHF and whose clinical presentation included hepatic and splanchnic congestion, together with echocardiographic evidence of tricuspid regurgitation and distended inferior vena cava without respiratory variation. These patients were compared to 28 nondiabetic patients of whom 14 were hospitalized with acute left heart failure (LHF) and 14 with heart disease but no heart failure (HDNHF). #### Summary of Results Serum glucose (mean ± SEM): DecompHF, 105.41 ± 4.08 mg/dL; Acute LHF, 94.86 ± 3.96 mg/dL; HDNHF, 124.57 ± 11.72 mg/dL. Serum glucose exceeded 140 mg/dL in only 3 patients with DecompHF (144, 154 and 157 mg/dL). #### Conclusions In nondiabetic patients hospitalized with DecompHF that included hepatic and splanchnic congestion, serum glucose of >140 mg/dL was rarely seen on admission and when present was mild (<160 mg/dL). Hyperglycemia is also infrequent in nondiabetic patients hospitalized with acute LHF or HDNHF. The absence of hyperglycemia on admission calls into question the potential risk of hypoglycemia and associated adverse cardiovascular events that could accompany the empirical use of intensive insulin therapy in these patients. ### 76 INSULIN-LIKE GROWTH FACTOR I DOWNREGULATES PROATHEROGENIC 12/15-LIPOXYGENASE IN VIVO AND IN VITRO C. Vaughn, S. Sukhanov, Y. Higashi, S. Shai, P. Delafontaine *Tulane University, New Orleans, LA.* #### Purpose of Study We have shown that 12/15-lipoxygenase (LOX) mediates important proatherogenic oxidized low density lipoprotein (OxLDL)-induced effects in smooth muscle cells (SMC), namely, cell apoptosis and downregulation of the insulin-like growth factor I (IGF-1) receptor. In addition, LOX mediates macrophage (MΦ) adhesion to atherosclerotic plaque. Recently we reported that infusion of IGF-1 into Apolipoprotein E-deficient (ApoE-/-) mice suppresses MΦ plaque infiltration and atherosclerosis; however, molecular mechanisms mediating these anti-atherogenic effects are unclear. This study was conducted to further explore such mechanisms. #### Methods Used To study the potential role of LOX in IGF-1-induced effects, ApoE-\- mice were injected bi-daily with human recombinant IGF-1 (0.7 mg/kg/day) for seven days. LOX aortic gene expression was measured using atherosclerosis-focused PCR arrays, and was confirmed by traditional RT-PCR gene expression analysis. To determine if the IGF-1-induced LOX expression decrease in the atherosclerotic aortas could be attributed to specific cell lineage, endothelial cells, SMC, and THP-1 derived macrophages were exposed to IGF-1 (10 ng/ml, 50 ng/ml, 24 h) and LOX gene expression was analyzed. Lastly, to model in vivo conditions, SMC or MΦ were exposed to OxLDL or native LDL (control, 80 ug/ml, 16 h) and 14,15-leukotriene (a product of LOX-specific enzymatic reaction) levels were measured in conditioned media by ELISA. #### Summary of Results IGF-1 decreased LOX aortic gene expression by 64 ± 6%. Similarly, IGF-1 dose-dependently decreased LOX gene expression in macrophages (IGF-1, 10 ng/ml: 0.81; IGF-1, 50 ng/ml: 0.51 vs. control: 1.0, fold changes, RT-PCR). IGF-1 treatment on endothelial and smooth muscle cells showed no significant effects. OxLDL induced a dramatic increase in LOX activity levels in macrophages (20-fold vs. 1.0, control), and a smaller increase in LOX activity in smooth muscle cells (18-fold vs. 1.0, control). #### Conclusions In summary, IGF-1 suppresses vascular LOX expression in ApoE-\- mice and also induces cell type-specific LOX downregulation in human macrophages. Our data suggests that the ability of IGF-1 to downregulate LOX plays an important role in its anti-atherogenic effect. ### 77 SECONDARY HYPERPARATHYROIDISM AND HYPOVITAMINOSIS D IN AFRICAN-AMERICAN PATIENTS HOSPITALIZED WITH DECOMPENSATED BIVENTRICULAR FAILURE. REPRODUCIBILITY AND SUMMER VERSUS WINTER MONTHS A.D. Whitted, S. Ali, A.U. Shahbaz, H. Zafarullah, K.P. Newman, R.C. Davis, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN.* #### Purpose of Study Nine consecutive African-American (AA) patients, without renal failure, who were hospitalized at the Regional Medical Center (MED) in Memphis (latitude 35°N) with decompensated biventricular failure (DecompHF), in February, 2005, were found to have secondary hyperparathyroidism (SHPT) with elevated plasma parathyroid hormone (PTH; >65 pg/mL); this included 5 patients who were newly diagnosed and not receiving medical treatment (*Am J Med Sci* 2006;331:30-4). During August, 2005, 20 AA hospitalized with DecompHF were found to have ionized hypocalcemia with SHPT and vitamin D deficiency (serum 25(OH)D < 30 ng/dL) (*Am J Med Sci* 2006;332:112-8). The reproducibility of these findings and the role of summer vs. winter months in their appearance was not considered in these earlier reports. #### Methods Used Accordingly, we retrospectively compared AA patients with EF < 30% due to a dilated cardiomyopathy of ischemic or nonischemic origin, who were consecutively admitted to the Cardiology Service at the MED with DecompHF: a) 13 (10 M; 58.9 ± 1.7 yrs) and 13 (10 M; 53.2 ± 3.5 yrs) patients hospitalized during either February, 2007 or February, 2008, respectively; and b) the 13 patients seen in February, 2008 and 12 others (10 M; 34.8 ± 5.3 yrs) seen during August, 2008. The clinical presentation of DecompHF included: jugular venous distention; tricuspid regurgitation; and bilateral lower extremity edema; while echocardiographic evidence included a dilated inferior vena cava without respiratory variation. Serum creatinine in all patients was <2.0 mg/dL). #### Summary of Results (mean ± SEM) #### Conclusions Thus in AA hospitalized here in Memphis, our retrospective study confirms SHPT and hypovitaminosis D to be covariants of DecompHF irrespective of the time of year. Plasma PTH and serum 25(OH)D should be routinely monitored in AA with DecompHF and appropriate corrective measures taken. View this table: [Table11](/content/57/1/301/T11) ### 78 THE THYMUS AND THYMULIN IN THE HYPERTENSION AND CARDIAC FIBROSIS FOUND IN RATS WITH ALDOSTERONISM A.C. Wright, Y. Sun, S.K. Bhattacharya, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN.* #### Purpose of Study Aldosterone/salt treatment (ALDOST) leads to a proinflammatory vasculopathy involving lymphocytes that contributes to hypertension and cardiac pathology. The thymus, integral to lymphocyte processing, undergoes accelerated involution during ALDOST. Hypozincemia and/or the release of corticosterone by an activated hypothalamic-pituitary-adrenal axis may each be contributory. Thymulin (Thy) production, a Zn2 + -dependent anti-inflammatory cytokine released by the thymus, may decline to favor a proinflammatory phenotype. Herein, we addressed the potential role of thymic involution and loss of thymulin on the hypertension and cardiac fibrosis associated with ALDOST. #### Methods Used Eight-wk-old male Sprague-Dawley rats receive ALDOST (0.75 μg/h by implanted minipump), together with 1% NaCl/0.4% KCl in drinking water for 4 wks. In addition, 4 cotreatments were studied: RU486, a glucocorticoid receptor antagonist (8 mg/day by gavage); a Zn2 + supplement alone (dietary, 40 mg/day); an infusion of Thy alone (0.7 μg/day) or in combination with ZnSO4. Age-/gender-matched rats served as controls. We monitored: systolic blood pressure(SBP); thymus weight; plasma Thy; and collagen volume fraction (CVF; %), a marker of fibrosis. #### Summary of Results Compared to controls, SBP was elevated (*P* < 0.05) by ALDOST (107 ± 7 vs. 195 ± 8 mm Hg) and was not reduced by cotreatment with RU486, ZnSO4, thymulin, or Thy + ZnSO4. Thymic weight was reduced (*P* < 0.05) compared to controls (0.18 ± 0.02 vs. 0.58 ± 0.05 mg) and this involution was not prevented by any of the cotreatments. Plasma Thy was reduced (*P* < 0.05) compared to controls (0.43 ± 0.01 vs. 0.55 ± 0.06 ng/mL) and was restored by Thy infusion alone or Thy + ZnSO4 (0.50 ± 0.08 and 0.53 ± 0.02 ng/mL), but not ZnSO4. The rise in CVF seen at 4 wk ALDOST (8.6 ± 1.7% vs. 2.4 ± 0.6% controls; *P* < 0.05) was not prevented by any cotreatment. #### Conclusions An accelerated involution of the thymus and reduced plasma Thy accompanied ALDOST and were not prevented by cotreatment with ZnSO4, Thy, or RU486. The hypertension and fibrosis seen at wk 4 ALDOST was not prevented by cotreatment with ZnSO4 or Thy alone or in combination. These findings suggest the thymus and Thy do not contribute to the proinflammatory phenotype. ### 79 ROLE OF EMOTIONAL STRESS IN TAKO-TSUBO CARDIOMYOPATHY Y. Yaqub, J. Suarez, K. Nugent, A. Perez-Verdia *Texas Tech University Health Science Center, Lubbock, TX.* #### Purpose of Study Tako-tsubo syndrome is a transient cardiomyopathy characterized by apical ballooning visualized by ventriculography. This syndrome is usually precipitated by acute emotional stress and is also referred to as a stress cardiomyopathy. #### Methods Used We analyzed the impact of emotional stress on clinical variables, echocardiographic characteristics, and short term outcomes in tako-tsubo patients identified during a 12 month period. Retrospective chart review was done with IRB approval. #### Summary of Results 11 patients presented with tako-tsubo syndrome (1 man, 10 women) during Jan07 - Dec07. Mean age was 53.8 + 12.6 years, lower than previous reports. 27% of patients were less than 50 years of age. Patients were divided into those presenting with predisposing emotional stress (6/11, 54.5%) and those with no obvious stressors (5/11, 45.5%). An emotional stressor was defined as an emotionally distressful event (death of family member, family feud, anxiety) occurring within preceding 30 days. Mean troponin T level in stress group was 0.57 (range-0.12-1.18) compared to 0.51 (range-0.03-2.06) in non-stress related group. Mean creatinine was 0.7 + 0.2 mg/dl. Apical ballooning was uniformly present; anterior wall hypokinesia/dyskinesia was present in 67% of patients (4/6) in emotional stress group and 80% of the non-stress group (4/5). The mean LVEDP was 15.8 + 8.1 mmHg in whole cohort (mean 14.5 in the stressed group and 17.8 in non-stressed group). Infection, either sepsis or pneumonia, was present in 40% of the non-stress group (2/5) and 17% of the emotional stress group (1/6). Emotional stress was positively correlated with length of stay (*P* = 0.04), the presence of ST-segment changes on ECG (66.7% vs. 40%, *P* = 0.42), and higher ejection fractions (*P* = 0.012). #### Conclusions Although stress plays a major role in tako-tsubo syndrome, we did identify non emotional stress-related cases (45%) with idiopathic tako-tsubo syndrome found in 3/11 (27%) patients. Patient with emotional stress had more ST segment changes, higher EF (*P* = 0.012), lower LVEDP (14.5 vs. 17.8 mmHg), and longer length of stay (*P* = 0.04) as compared to non-stress related patients. To best of our knowledge, this is first study which reports the clinical, echocardiographic and outcome differences in emotional stress vs. non-stress related tako-tsubo syndrome. ### 80 DIFFERENTIAL REGULATION OF UBIQUITIN LIGASES ATROGIN-1 AND MURF-1 IN ANGIOTENSIN II-MEDIATED SKELETAL MUSCLE ATROPHY T. Yoshida, L. Semprun-Prieto, S. Sukhanov, P. Delafontaine *Tulane University School of Medicine, New Orleans, LA.* #### Purpose of Study Advanced congestive heart failure is associated with activation of the renin-angiotensin system and skeletal muscle atrophy. Angiotensin II (Ang II) infusion in mice produces cachexia secondarily to increased muscle proteolysis and also decreased levels of circulating and skeletal muscle IGF-1. Two E3 ubiquitin ligase genes Atrogin-1 and MuRF-1 are known to be upregulated in skeletal muscles of Ang II-infused animals and are important in mediating skeletal muscle proteolysis via the ubiquitin-proteasome system (UPS). The purpose of this study is to determine mechanisms linking Atrogin-1 and MuRF-1 expression and IGF-1 signaling. #### Methods Used Time-course dependent expression of Atrogin-1, MuRF-1, IGF-1 and IGF-1 receptor (IGF1R) was analyzed in skeletal muscles of Ang II infused mice by quantitative RT-PCR. #### Summary of Results Expression of Atrogin-1 and MuRF-1 were elevated one day after the initiation of Ang II-infusion (4.92 ± 0.86 and 7.82 ± 2.02 fold, respectively) and the expression levels gradually decreased on day 4 and day 7. On the other hand, the expression level of IGF-1 was not changed on day 1 and day 4, whereas a significant reduction (0.50 ± 0.09 fold) was observed on day 7. The expression of IGF1R was increased on day 1 and day 4 (1.32 ± 0.08 and 1.36 ± 0.09 fold, respectively), and returned to basal levels on day 7. Contrary to wild-type (WT) mice, there was no significant reduction of skeletal muscle weight in mice overexpressing IGF-1 specifically in skeletal muscle (MLC-IGF-1 mice) infused with Ang II. In skeletal muscles of MLC-IGF-1 mice, the basal and Ang II-induced expression of Atrogin-1 was significantly repressed compared to WT mice. On the other hand, basal expression level of MuRF-1 in skeletal muscles of MLC-IGF-1 mice was not different from WT animals. Furthermore, after Ang II-infusion, MuRF-1 expression was upregulated both in WT and MLC-IGF-1 mice. #### Conclusions These data demonstrate that the expression of Atrogin-1 and MuRF-1 is differentially regulated in skeletal muscles of Ang II infused mice. IGF-1 prevention of Ang II induced atrophy is mediated via the ability of IGF-1 to repress Atrogin-1 expression, rather than MuRF-1 expression. ### 81 CORRECTION OF MARKED VITAMIN D DEFICIENCY IN AFRICAN-AMERICANS WITH HEART FAILURE. RESPONSE TO A LARGE-DOSE VITAMIN D SUPPLEMENT A. Zia, M.D. Nelson, R.E. Morrison, K.P. Newman, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN.* #### Purpose of Study A reduction in serum 25(OH)D in keeping with vitamin D deficiency (<30 ng/mL) is quite prevalent in African-Americans (AA) residing in Memphis, TN (latitude 35°N), with or without heart failure (*Am J Med Sci* 2008;335:292-97). In AA housebound with symptomatic heart failure, the degree of hypovitaminosis D can be of moderate (10-20 ng/mL) to marked (<10 ng/mL) severity. Melanin is a natural sunscreen and hence the darker the skin, the longer sunlight exposure needed to begin vitamin D steroidogenesis. A regimented protocol of outdoor ultraviolet B exposure to correct vitamin D deficiency is not practical in these patients. We therefore turned to an oral vitamin D supplement. However, the dose and duration of treatment required to correct serum 25(OH)D to >30 ng/mL was uncertain. We selected ergocalciferol (50,000 units) given by mouth once weekly for 8 wks. #### Methods Used Over the past several months, we have been enrolling AA patients with heart failure (EF < 35%) of diverse etiology and documented hypovitaminosis D (<30 ng/mL) into an open-label study. In addition to today's standard of care, these patients receive 50,000 units of oral ergocalciferol, once weekly for 8 wks. Serum 25(OH)D is assayed at baseline and 8 wks treatment. #### Summary of Results To date, 5 patients (3 M; 50.4 ± 4.4 yrs) have completed the 8-wk study. At the time of entry, their baseline 25(OH)D was 15.22 ± 2.98 ng/mL; at 8 wks treatment it had risen to 34.88 ± 4.09 ng/mL. No untoward events or side effects have occurred with this regimen. Subjectively, patients report an increased sense of well-being. #### Conclusions These preliminary findings suggest a large oral dose of ergocalciferol given once weekly for 8 wks will raise moderately to severely depressed serum 25(OH)D levels to >30 ng/mL and thereby correct hypovitaminosis D in AA residing in Memphis with heart failure. A regimen that will sustain 25(OH)D at >30 ng/mL needs to be developed and is under investigation. The results of this ongoing study will be collated with current findings for presentation at the 2009 SSCI meeting. ### 82 HYPOVITAMINOSIS D AND PARATHYROID HORMONE LEVELS IN PATIENTS WITH CORONARY ARTERY CALCIFICATION A.A. Zia1, A. Munir2,1 * 1University of Tennessee Health Science Center, Memphis, TN and 2Veterans Administration Medical Center, Memphis, TN*. #### Purpose of Study Coronary artery calcification is frequently associated with atherosclerotic disease. Abnormal levels of Ca2 + homeostasis mediators, such as vitamin D and PTH, have been implicated in the appearance of coronary artery calcification. We hypothesized that in patients with fluoroscopically proven coronary calcification, hypovitaminosis D could lead to secondary hyperparathyroidism facilitating calcification in the atherosclerotic coronary arteries. #### Methods Used We selected 27 patients, average age 64 (51-83) with coronary calcification apparent on fluoroscopy from patients referred for elective coronary angiography at our cath lab. Levels of 25 OH vitamin D, PTH, iCa, and phosphate were measured. Patients were excluded if they had serum creatinine >2.0, metabolic bone disease, primary hyperparathyroidism, gastric resection, inflammatory bowel disease, receiving insulin, glucocorticoids, growth hormone, thyroxine, altered Ca2 + homeostasis such as sepsis, pancreatitis, recent blood transfusion, recent surgery, excessive alcohol usage, metabolic alkalosis. #### Summary of Results 24 out of 27 patients (88%) with coronary calcification had serum 25 OH vitamin D < 30 ng/mL, the lower limit of normal. PTH levels, however, were found to be normal (<65 pg/mL) in 22 out of 27 (81%) patients. Five patients had mild elevations of PTH levels. All of these five patients had low vitamin D levels. Levels of iCa, and PO4 were within normal levels. #### Conclusions A high incidence of hypovitaminosis D was found in patients with fluoroscopically apparent coronary artery calcification. However, secondary hyperparathyroidism was not present in majority of patients as originally hypothesized. The exact role of hypovitaminosis D in calcification of atherosclerotic coronary arteries needs further investigation. ## **Cardiovascular Case Report Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 83 PULMONARY VEIN SYNOVIAL SARCOMA CAUSING MITRAL VALVE OUTFLOW TRACT OBSTRUCTION AND LEFT LUNG INVASION W. Chokesuwattanaskul, L. Jenkins *Texas Tech University Health Sciences Center, Lubbock, TX.* #### Case Report We report a case of pulmonary vein synovial sarcoma with extensive intra-left atrial spread causing mitral valve obstruction and left lung invasion. The patient is a 26 year-old Hispanic man who has complained of progressive left-sided chest pain and two episodes of near-syncope in the past few months. We found a large mass in left hemithorax and a 5-cm intra-left atrial mass with mitral valve outflow tract obstruction. He underwent excision of the left atrial tumor, revealing its origin from left superior pulmonary vein. Pathological and histochemical findings were consistent with monophasic synovial sarcoma. To our knowledge, this is the first reported case of pulmonary vein monophasic synovial sarcoma extending to the left atrium and causing mitral valve outflow tract obstruction. Echocardiogram showed large pedunculated mass, 4.4 × 2.4 cm-sized in left atrium ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F3.medium.gif) [Figure.](/content/57/1/301/F3) Figure.   ### 84 AN UNUSUAL CARDIAC DEFECT IN A PATIENT WITH CARDIOFACIOCUTANEOUS SYNDROME H.C. DeSena1,2, D.M. Niyazov3, P.E. Parrino4, V.W. Lucas5, D.S. Moodie5 * 1Ochsner Clinic Foundation, New Orleans, LA; 2Tulane University, New Orleans, LA; 3Ochsner Clinic Foundation, New Orleans, LA; 4Ochsner Clinic Foundation, New Orleans, LA and 5Ochsner Clinic Foundation, New Orleans, LA*. #### Case Report Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder resulting from a sporadic autosomal dominant mutation and is characterized by multiple congenital abnormalities, including congenital heart disease (CHD), mental retardation (MR), short stature, characteristic dysmorphic features, and abnormalities of the skin, eyes, gastrointestinal tract, and central nervous system. The patient in this case presented with atrial fibrillation and was found to have an aneurysm of left atrial appendage caused by a jet of mitral regurgitation directed toward the left atrial appendage. This rare mitral valve abnormality has not previously been reported in the literature in association with the CFC syndrome. The patient underwent mitral valve replacement and the Cox-Maze III procedure and has remained asymptomatic from a cardiovascular standpoint. He has since been given a diagnosis of Cardiofaciocutaneous syndrome. ### 85 VENTRICULAR FIBRILLATION IN A PATIENT WITH POMPE'S DISEASE H.C. DeSena1,2, C.S. Snyder3, D. Superneau4, M.R. Brumund5 * 1Ochsner Clinic Foundation, New Orleans, LA; 2Tulane University, New Orleans, LA; 3Ochsner Clinic Foundation, New Orleans, LA; 4Genetic Services of Louisiana, Baton Rouge, LA and 5Pediatric Cardiology Associates, Baton Rouge, LA*. #### Case Report Pompe's disease is a rare autosomal recessive genetic disorder resulting from a deficiency of the acid alpha glucosidase (GAA) enzyme. A lack of GAA results in accumulation and deposition of glycogen in cardiac muscle, leading to hypertrophic cardiomyopathy and arrhythmias. Infantile Pompe's disease is a uniformly fatal disease when left untreated; however, earlier detection of the disease with newborn screening may allow for earlier diagnosis and treatment. Review of the literature revealed that arrhythmias have been shown to occur in patients with Pompe's disease with the use of volatile anesthetics and propofol. Clinicians caring for these patients must be aware of their risk of ventricular fibrillation during general anesthesia and be prepared for its appropriate treatment. We report a patient with Pompe's disease who experienced ventricular fibrillation while under general anesthesia. The patient was successfully resuscitated and is currently receiving enzyme replacement therapy. ### 86 PROGRESSIVE THROMBOSIS OR A PORCINE AORTIC VALVE B.J. Rochon *LSUHSC, New Orleans, LA.* #### Case Report 72 year old male, 2 years post operative porcine aortic valve replacement for calcific aortic stenosis. The patient was admitted for abdominal pain secondary to acute pancreatitis. No chest pain or dyspnea. PMH:Aortic Stenosis status post Porcine Aortic Valve Replacement in 7/06 Non-obstructive CAD via Coronary Angiogram in 6/06 Normal LV Function 6/06 Hypertension BPH 3-4 ETOH drinks/night 3-4 Cigars per evening No illicit drugs Hospital course The patient was treated medically including intravenous fluids, analgesics, and bowel rest. Further testing was performed including a 2-Dimensional echocardiogram. During early treatment and evaluation. the patient suddenly became hemodynamically unstable, ACLS protocol was performed, and the patient expired. Autopsy: Chronic Pancreatitis, two peripancreatic pseudocysts, one leaking, generalized peritonitis and ileus. The heart weighed 779 grams with marked LVH (3.3 cm wall). Acute Thrombosis and Obstruction of Bioprosthetic Aortic Valve. small dissecting aneurysm extended astride the insertion of the prosthetic valve anterior to the takeoff of the right coronary artery connecting the aortic to the ventricular cavities (perivalvular leak). Echo Good LV Systolic Function Left Ventricular Hypertrophy Left Atrial Enlargement Bioprosthetic Aortic Valve with Moderate AS Moderate AR When compared to echo of 8/06 a periprosthetic leak may have worsened, but turbulence and jet eccentricity makes the valve evaluation more challenging. ECG(picture) Gross and microscopic sections of thrombosed porcine valve. Dry, friable blood clot (antemortum clot) is adherent to the valve leaflets and root. Valve leaflets are intact, no tears or rupture, without gross or microscopic evidence of septic vegetations. Blood clot adherent to valve leaflets shows recent thrombosis features - very recent to several days old (acute thrombosis). Blood clot burrow seen in aortic ring around right coronary artery ostium shows peripheral organization indicating it is weeks to months old (chronic thrombosis). Microscopic sections Conclusion of Death Pancreatitis probably produced a hypercoagulalble state, which produced propagation of the thrombus upon the thrombotic nidus in the perivalvular leak. Thus, sudden death was due to occlusion of the left ventricular outflow tract by thrombus. ### 87 CHRONIC STRESS RESULTING IN BROKEN HEART SYNDROME B. Saeed, N. Shahid, A Mutgi *University of Toledo Medical Center, Toledo, OH.* #### Case Report Broken heart syndrome/Takotsubo cardiomyopathy is a recently described stress induced cardiomyopathy associated with symptoms suggestive of acute coronary ischemia including chest pain, ST changes and elevated cardiac enzymes. Often the syndrome is triggered by profound, acute, physical or psychological stress and has an increased incidence in post menopausal women. We describe a patient admitted with non specific complaints and subsequently developed Takotsubo's cardiomyopathy confirmed by intra-cardiac ventriculography. Our patient had no precipatating acute events. A 64 yrs old Asian female presented with cramping abdominal pain of 6 hours duration. Physical exam was unremarkable except for diffuse abdominal tenderness. WBC was 14 K with an elevated neutrophil count. Abdominal x- ray showed mild ileus. Electrocardiogram and cardiac enzymes were normal. Within 3 hours of admission the patient developed retrosternal chest pain radiating to her neck and left arm. Repeat EKG showed ST-elevation in V1 and V2 and cardiac enzymes were elevated with a troponin of 1.14. Emergent cardiac catheterization showed normal coronary arteries but left ventriculography revealed a severely reduced ejection fraction with diffuse aneurismal dilation of the mid and apical ventricular segments consistent with takotsubo cardiomyopathy. Subsequently an in depth history of the patient revealed that she had been under increased stress over the last several months due to the death of her parent. The patient received supportive care including aspirin, beta blocker, ACE inhibitor and statin therapy. She was discharged home on the third day of her admission in good condition. The name takotsubo's cardiomyopathy comes from the peculiar shape of the left ventricle seen during intra-cardiac ventriculography which resembles a Japanese pot used for catching octopuses called a "takotsubo", literally meaning "octopus pot". It is thought to be mediated by microvascular ischemia secondary to acute stress. Unlike the previously reported cases our patient presented with atypical abdominal pain and ileus and developed acute MI like changes under observation. Our patient had been under stress for previous 6 months with no precipating events. The mechanism of chronic stress mediating this condition remains unclear. ### 88 PRIMARY HEPATIC SARCOMA EXTENDING INTO THE RIGHT ATRIUM F.E. Wilklow, D.L. Glancy, N. Jain *LSU New Orleans, New Orleans, LA.* #### Case Report A sixty five year old gentleman with the past medical history of hepatitis C, cirrhosis, and COPD had multiple admissions for shortness of breath at Medical Center of Louisiana in New Orleans. Routine echocardiography revealed an intra cardiac mass causing right ventricular inflow obstruction. Patient had a biopsy which revealed a primary hepatic sarcoma extending through the descending vena cava into the right atrium. Primary hepatic sarcomas are extremely rare tumors comprising less than 0.01% of hepatic tumors. Epidemiologic studies suggest some clinical correlation with oral contraceptive use, and no correlation with cirrhosis or chronic hepatitis. Review of the literature found no cases of confirmed hepatic sarcoma extending into the right atrium causing obstruction. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F4.medium.gif) [Figure.](/content/57/1/301/F4) Figure.   ## **Clinical Epidemiology and Preventive Medicine Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 89 RELATION OF GLUCOSE TOLERANCE AND INSULIN RESISTANCE TO LEFT VENTRICULAR STRUCTURE AND FUNCTION IN AFRICAN AMERICANS (FROM THE JACKSON HEART STUDY) J.C. Cook, H.A. Taylor, T.E. Samdarshi, D.F. Sarpong, E.R. Fox *University of Mississippi School of Medicine, Jackson, MS.* #### Purpose of Study The effect of glucose tolerance and insulin resistance (IR) on left ventricular (LV) structure and both systolic and diastolic function in African Americans (AA) is not well-described despite high rates of diabetes and cardiovascular morbidity in this group. #### Methods Used Using sex-specific analysis in Jackson Heart Study on participants undergoing echocardiograms in exam 1 (2001-2004), we assessed the relation of LV mass index, wall thickness, ejection fraction and mitral early to late (E/A) diastolic filling ratio to glucose tolerance (GT) category and across quartiles of homeostasis model assessment of insulin resistance (HOMA-IR) scores adjusting for age, systolic blood pressure, antihypertensive medications and body mass index. General linear models were used for continuous variables and logistic regression models were used for dichotomous variables. #### Summary of Results Of 2,540 participants in the study population(62.2% female), percentages of women and men in each category of GT were 46.5% and 27.9% for normal GT, 7.4% and 5.9% for impaired GT, and 8.3% and 4.0% for diabetes respectively. LV mass index and posterior wall thickness were significantly related to GT categories in both women and men.(*P* = 0.0001 and 0.0064 respectively for LV mass index and *P* = 0.0202 and 0.0264 respectively for posterior wall thickness.) Interventricular septal wall thickness was significantly related to GT in women.(*P* = 0.0063) Among participants with normal GT, LV mass index was independently related to IR across quartiles of HOMA-IR scores (*P*-trend = 0.0408 and 0.0401 in women and men respectively). Wall thicknesses were similarly related to IR in this group. LV mass index and wall thickness were not significantly related to IR among participants with abnormal GT. Ejection fraction and mitral E/A ratio were not independently related to GT category or IR. #### Conclusions This study represents the largest community-based analysis of the affect of GT and IR on LV structure and function in middle-aged African Americans. We found LV mass index and wall thickness was independently related to both GT and IR in AA women and men. ### 90 TEEN DRIVING RELATED EMERGENCY DEPARTMENT VISITS TO A URBAN PEDIATRIC EMERGENCY DEPARTMENT A. Edwards1,2, W.D. King1, K. Monroe1 * 1University of Alabama, Birmingham, AL and 2University of Alabama, Birmingham, AL.* #### Purpose of Study Motor vehicle crashes (MVCs) are the leading cause of death and disability among Alabama teens. Birmingham, Alabama ranks fifth in deadliest cities for teens drivers. #### Methods Used A retrospective chart review of teen driver MVCs (ages 13- 19 years) was conducted at The Children's Hospital of Alabama from June 2007 through March 2008. Descriptive data (demographics and crash details) were analyzed using Excel® and Epi-Info®. #### Summary of Results A total of 75 charts were identified using an ED visit database. Of those, 70 involved teenage drivers (57% females; 44% African American, 53% Caucasian). Auto vs Auto accounted for 50% of crashes (11% being auto alone), 13% auto vs stationary object and 25% not documented. Overall, 18 (25%) were admitted to hospital with length of stay ranging from 1 to 14 days. Airbag deployed in 37% with no airbag deployment in 22% and 41% of charts had no airbag documentation. Peak day of week for ED visit was Tuesday (23%) and peak month was October (23%), similar to state wide data. 66% were restrained (60% with lap/shoulder belt), while in 7% restraint was undocumented #### Conclusions While patient demographics and temporal trends provided in this sample are similar to statewide statistics on MVC's, our teen MVC restraint use was significantly below overall seatbelt use for the state (60% vs 89%). Teen MVC visit admission rates are 2.5 times the overall ED visit admission rate. Important data such as cell phone use, passengers, speed, airbag deployment and others are commonly undocumented. ### 91 ADIPOSITY IN CHILDHOOD AND RACE PREDICT C-REACTIVE PROTEIN AND ADIPONECTIN IN YOUNG ADULTHOOD: THE BOGALUSA HEART STUDY D. Toprak, A. Toprak, W. Chen, J.H. Xu, S. Srinivasan, G. Berenson *Tulane Center for Cardiovascular Health, New Orleans, LA.* #### Purpose of Study Cardiovascular (CV) disease evolves during a considerable period, beginning from childhood. Elevated high sensitive c-reactive protein (hsCRP) and low adiponectin levels are markers of CV events in adulthood. The aim of this study was to determine the childhood risk factor predictors of hsCRP and adiponectin in adulthood. #### Methods Used As a part of a longitudinal cohort survey, 835 eligible black and white young adult subjects (age range 24 to 42 years, average 34 years, 43% men, 31% black) who had CV risk-factor variable data from their childhood (20 years earlier, age range 5 to 18 years, average 14 years) were selected for this study. #### Summary of Results Serum hsCRP level was higher in white women than white men (3.3 ± 3.6 vs 2.0 ± 2.4 mg/dl, *P* < 0.001). Both white and black women had higher serum adiponectin levels compared with white and black men (10.2 ± 4.5 vs 7.4 ± 3.5 μg/ml and 8.3 ± 4.3 vs 6.3 ± 3.2 μg/ml, respectively, *P* < 0.001 for both). White women had higher serum adiponectin level than black women (*P* < 0.001). In their childhood, the sum of triceps and subscapular skinfold thickness was significantly higher in girls in both races, and white boys had higher skinfold thickness than black boys. However, body mass index (BMI) was not significantly different among race and gender groups in childhood. Linear regression models were created to determine the predictors of adulthood hsCRP and adiponectin levels. Childhood skinfold thickness (*P* < 0.001), female gender (*P* = 0.001), childhood total/high density lipoprotein cholesterol ratio (*P* = 0.009) and black race (*P* = 0.015) were significant predictors of adulthood hsCRP. Female gender (*P* < 0.001), low BMI in childhood (*P* < 0.001) and white race (*P* = 0.001) were the significant predictors of adiponectin level in young adulthood. #### Conclusions Childhood adiposity, represented by the sum of triceps and subscapular skinfold thickness and BMI, and black race predict higher hsCRP and lower adiponectin levels in their adulthood. Skinfold thickness was a stronger predictor for hsCRP than BMI. On the other hand, BMI was stronger predictor for serum adiponectin than skinfold thickness. ## **Endocrinology and Metabolism Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 92 INSULIN RESISTANCE IN DM2: ANALYSIS OF GENES IN THE TNF-α MODEL IDENTIFIES NEW TARGETS D. Carrigan1, O. Odunusi1, G. Majumdar1,2, N. Lenchik1, I. Gerling1, S. Solomon1,2 * 1University of Tennessee Health Science Center, Memphis, TN and 2VAMC (Memphis);, Memphis, TN*. #### Purpose of Study Metabolic Syndrome is a variant of Diabetes Mellitus 2 (DM2), in which a major component is insulin resistance (IR), thought to be caused by TNF-α. #### Methods Used We modeled IR in H411E liver cells (LCs) in tissue culture, using TNF-α (T) and Insulin (I). Three independent samples of RNA from each group were analyzed on expression arrays (rat, Affymetrix). In addition, we analyzed data from a paper in Diabetes 51: 3176, 2002 (Ruan/Lodish) studying effects on gene expression of TNF-α alone in adipose tissue (AT). We analyzed comparable data (T alone) from both experiments together using DAVID, Webgestalt, and Ingenuity. #### Summary of Results From our past data in LCs, when examining TNF-a induced IR (T-IR) after Hierarchiacal clustering, we identified 33 genes in LCs showing T-IR. These 33 were then subjected to Ingenuity pathway analysis. This produced a single molecular network which was centered around: insulin receptor; TNF-α; Akt; p38-MAPK; TGFb1; MYC and transcription factors, SMAD and STAT1. When the Ruan/Lodish data in AT were analyzed and combined with our data from LCs, both examining only TNF-α incubation alone, we identified not only many of the above genes, but also unique, previously not seen genes and pathways, including the insulin signaling pathway linked to the major apoptosis pathway, through the P13 Kinase dephosphoryating phosphatase, PTEN. #### Conclusions We identified genes responding to TNF-α only in LCs and AT. We re-analyzed data from LCs, in which effects of of I were reversed by T + I. The sum of both data analyses identified genes that regulate: (a) signal transduction, including second messengers and cytokines; (b) transcription, translation, protein synthesis and degradation; and (c) energy balance, oxidation-reduction reactions and oxidative stress. Defective intramyocellular FA metabolism and inflammation involving the mitochondria could contribute to the IR. Furthermore, we identified PTEN as a unique newly identified gene linking insulin signaling to apoptosis in TNF-α induced IR. ### 93 CEREBRAL EDEMA BEFORE ONSET OF THERAPY IN NEWLY-DIAGNOSED TYPE 2 DIABERES K.A. Daniels, A.E. Morales Pozzo *University of Arkansas for Medical Sciences, Little Rock, AR.* #### Case Report Objective: To discuss the management of a rare case of cerebral edema before initiation of therapy in an adolescent with new onset type 2 diabetes. Research Design and Methods: The UAMS Institutional Review Board approved the review of medical records. Results: A previously healthy obese adolescent female suffered DKA-related cerebral edema before initiation of therapy. Prompt management was associated with complete recovery. Conclusions: DKA-related cerebral edema before treatment can occur in patients with new onset type 2 diabetes. Use of mannitol and hypertonic saline solution should be considered in the management of DKA-related cerebral edema. View this table: [Table12](/content/57/1/301/T12) Laboratory Data at Initial Presentation ### 94 PRIMARY HYPERPARATHYROIDISM IN PREGNANCY PRESENTING AS ACUTE PANCREATITIS IN 3RD TRIMESTER -A CASE REPORT A.N. Khan, M.G. Ganguli, S. Dagogo-Jack *University of Tennessee, Memphis, TN.* #### Case Report Less than 160 cases of primary hyperparathyroidism(PHPT) in pregnancy have been reported. Most of the cases describe patients in the first 2 trimesters. Surgery in trimester 3 is extremely rare as is PHPT presenting as acute pancreatitis, with less than 20 cases reported of the latter. A 27 years old Caucasian female with morbid obesity, chronic HTN, gestational DM, 30 weeks pregnant(G3P2A0), was transferred to the MED from a local hospital after receiving hydration and pamidronate for acute pancreatitis and hypercalcemia. She had a PTH of 218 pg/ml and a 2.6 cm nodule in left lower pole of thyroid per USG. She denied any h/o kidney stones, seizures, fractures, Vit D therapy, excessive calcium/milk/alkali intake, pancreatitis or hypercalcemia. Her previous 2 pregnancies had normal fetal outcomes. Physical exam was unremarkable. Surgery recommended conservative management and she was discharged after 5 days. Twelve days later, she was again transferred to the MED from the local hospital after receiving pamidronate for hypercalcemia with mild pancreatitis. Nasal Calcitonin, high dose vitamin D (for low vitamin D) and hydration were given. She was discharged after 8 days to follow up with endocrinology. PHPT in pregnancy has a high complication rate: 67% in mothers (nephrolithiasis, cystic osteoid fibrosis, pancreatitis, hypercalcemic crises), 80% in fetuses (death, miscarriage, preterm birth, intrauterine growth restriction, neonatal tetanic crisis, permanent hypoparathyroidism). If recognized in first 2 trimesters, parathyroidectomy is favored in trimester 2 to prevent the suppressive effect of prolonged maternal hypercalcemia on fetal parathyroids. However, reserving Trimester 3 surgeries for only symptomatic cases may increase the risk of complications from delayed intervention (18-25% in both fetuses and mothers) compared to a risk of only 5.9% in fetuses and 0% in mothers after surgery. There is limited data on the use of pamidronate in pregnancy. Three cases of hypercalcemia in pregnancy treated with pamidronate have been reported with good fetal outcomes. Hence, it is important for physicians to understand the risks of PHPT in pregnancy. They should be able to balance these with the postoperative risks in the third trimester of pregnancy. ### 95 PANHYPOPITUITARISM CAUSED BY A HYPOTHALAMIC MASS: A CASE REPORT A.N. Long1,2, A.N. Khan1,2, S. Solomon1,2 * 1University of Tennessee Memphis, Memphis, TN and 2Veteran Affairs Medical Center of Memphis, Memphis, TN.* #### Case Report The anatomical location of suprasellar meningiomas makes these tumors seem likely to cause significant compression of the pituitary gland and stalk. However, review of the literature revealed only one case of panhypopituitarism caused by a suprasellar meningioma. Our patient is a 56 year old male with a history of stage IIIB squamous cell carcinoma of the lung and hepatitis C, who was admitted to VAMC for altered mental status. CT of the head revealed a 2.8 cm suprasellar mass consistent with a meningioma. MRI Brain (no contrast) confirmed the mass as a meningioma with no obvious pituitary abnormalities. Hormonal work up showed panhypopituitarism and hypernatremia. Hypernatremia was thought to be caused by central diabetes insipidus, acute renal insufficiency, and decompensated cirrhosis. D5W, hydrocortisone and levothyroxine were given. Mental status and hypernatremia improved significantly. Neurosurgical team recommended observation without surgical intervention. Hypothalamic masses can be caused by a variety of space occupying lesions. These include gliomas, meningiomas, craniopharyngiomas, germinomas, chordomas and hamartomas. Metastases from solid cancers usually develop within the pituitary, but systemic diseases such as Hodgkin's lymphoma, leukemia, Histiocytosis X, and Wegner's granulomatosis can metastasize to the basal hypothalamus. Vascular lesions like aneurysms must also be considered in the differential diagnosis. Symptoms can include cachexia, euphoria, failure to thrive, precocious puberty in children, headache, seizure, visual loss and hyperactivity. In contrast to pituitary tumors, hypothalamic tumors more often cause posterior pituitary failure. Treatment plans are dependent on the underlying etiology of the lesion. The patient described above has radiologic images suggestive of a suprasellar meningioma causing panhypopituitarism. This case is of academic interest as it is an extremely rare cause of hypopituitarism. However, it also emphasizes the need to look at patients in a holistic view prior to pursuing a surgical workup that may not change clinical management or improve patient's quality of life. ### 96 A CASE OF GRAVES' DISEASE COMPLICATED BY PSYCHOSIS, THYROID STORM, AND THYROTOXIC PERIODIC PARALYSIS D. Malinowski, J. Fisher *UTHSC, Memphis, TN.* #### Purpose of Study A 26 year old Korean man was brought to ER by ambulance due to a change in mental status. Patient had not eaten or drunk for 3 days. For 3 to 4 weeks he had exhibited erratic behavior with uncontrolled anger, crying spells, and hallucinations and had lost 15 lbs despite increased appetite. P.E.: afebrile, pulse 160, regular; B.P. 155/96. He was lying in a fetal position, crying, occasionally screaming. No exophthalmos, moderate thyromegaly with prominent bruit, no heart murmur, no edema, tremor, or onycholysis, brisk DTR. #### Methods Used Lab: TSH< 0.01(0.34-5.6 mIU/ml), TT4 26.5 (4.1-10.9mg/dl), TT3 543 (87-178ng/dl), FT4 5.5 (0.58-1.64 mg/dl), FT3 13.7(2.3-4.2 pg/dl), Anti-TPO 1623 (0-34 U/ml), TSI- 176(<130); K-3.5 mg/dl. CBC, BMP normal. Urine drug screen, blood alcohol negative; enlarged heterogeneous thyroid on sonogram with increased vascularity. CT brain: normal. #### Summary of Results The pt. was placed on large doses of thionamides (initially PTU 400 mgq8h, later methimazole 30 mg q6h) and propranolol up to 160 mg q6h. Despite these therapies he became febrile and appeared to be in thyroid storm. After 10 days of treatment he developed hypokaliemia and had a respiratory arrest requiring ventilator for a week. With little improvement after 4 weeks in hospital, SSKI was added and subtotal thyroidectomy performed with prompt resolution of thyrotoxicosis and psychosis. Ten months later he remains off antipsychotics. #### Conclusions Thyroid storm, thyrotoxic periodic paralysis, and psychosis due to thyrotoxicosis are rare complications of hyperthyroidism. We report on psychotic depression in an Asian man with Graves' disease whose symptoms abated following thyroidectomy. Surgical thyroidectomy should be considered in thyrotoxic patients who are unresponsive to medical therapy or who manifest unremitting or life-threatening psychotic behavior. Thyrotoxic periodic paralysis is a potentially lethal condition characterized by muscle paralysis and hypokaliemia due to massive intracellular shift of potassium. Diagnosis is based solely upon clinical symptoms. It is frequently overlooked or misdiagnosed upon presentation, especially in the absence of overt signs of thyrotoxicosis. ### 97 HYPERCALCEMIA OF 26.5: ISOLATED PARATHYROID MALIGNANCY OR HEREDITARY SYNDROME? C.R. McCollum1, K. Pitman3, S. Bigler2, V. Vijayakumar4, M. Flessner1, J. Jenkins1, M. Horn1, A. Arnold5, C.A. Koch1 * 1Univ of Mississippi, Jackson, MS; 2Univ of Mississippi, Jackson, MS; 3Univ of Mississippi, Jackson, MS; 4Univ of Mississippi, Jackson, MS and 5Univ of Connecticut, Farmington, CT.* #### Case Report pHPT is common and rarely caused by germline mutations in predisposing genes (MEN1, RET, CaSR, HRPT2). Germline and somatic mutations in the HRPT2 gene are found in the HPT-JT syndrome and parathyroid cancer (PC). Pts with PC usually have higher blood calcium levels (>14 mg), intact PTH levels > 4x normal, and invasive tumors. #### Objective To illustrate mx of severe hypercalcemia and elucidate pathogenesis of parathyroid tumors. A 50-yo BM presented with altered mental status. S-calcium 26.5 mg, ion calcium 3.12 mmol, PTH 3722 pg, 25-OHD 12 ng, phos 3.8 mg, and creat 2.7 mg. EKG normal. W/u for pHPT revealed 1.6 cm mass inf to L thyroid and enlarged kidneys. During neck explor the parathyroid tu, ipsilateral parathyroid and thyroid gland were removed. Pathology showed encapsulated parathyroid neoplasm with capsular invasion and 5 neg LN. Postop, the pt developed normal mental status. At d/c, S-calcium was 9.8 mg, creat 3.5 mg, ion cal 1.3 mmol, and PTH 426 pg. MIBI-SPECT and F-18 FDG PET scans were neg. Neck US showed a 7 mm cystic area in the right thyroid. At 7 mo f/u, 25-OHD was raised to 84ng, PTH 135 pg, s-calcium 10.2 mg, ion cal 5.24 mg (<5.3), plasma CgA 173 ng (<225), creat 1.5 mg, and phos 3.4 mg, indicating persistent pHPT. The pt had no renal stones or features of MEN-1 nor did his fam members incl a 13-yo son and 18-yo daughter. BMD by DEXA, T score: - 3.0 forearm, - 1.7 spine, - 0.6 femur. Neck US: 17 mm cystic and a 6 × 6 mm hypoechoic area in right thyroid. MIBI-SPECT and CT scan head and neck, & germline and somatic mutation analyses for HRPT2 gene pending. This case illustrates when to consider familial pHPT and/or PC, as our pt had postop persistently elevated PTH levels despite correction of vitD defiency and normalizing renal function. Pre- and intraop, there was no evidence of multiglandular disease or spread. Postop imaging studies initially nonsuspicious but 7 mo f/u raised concern. In this setting, germline mutation analysis for HRPT2 gene may aid in clinical mx of not only pt but also children with 50% chance to develop pHPT if father positive. ### 98 RISK FACTORS FOR METABOLIC SYNDROME IN YOUNG HEALTHY SOUTH ASIANS V. Monteiro, S. Chhabria, N. Abbas, G. Monteiro, Y. Wu, R. Sharma, L.F. Amorosa *UMDNJ-Robert Wood Johnson Med Sch, New Brunswick, NJ*. #### Purpose of Study High rates of metabolic syndrome have been observed among young South Asians (from India, Pakistan and Bangladesh) residing in the United States who present with Acute coronary syndrome. To identify young South Asians with signs of metabolic syndrome and advise them of their risk, we conducted health surveys of South Asian residents in New Jersey and compared risk variables in young vs. older cohorts. #### Methods Used Blood pressure, body mass, glycemic and lipid measures were taken thoughout the day in ambulatory volunteers who were attending social gatherings thoughout New Jersey. Data were entered into an SPSS database and categorized into two cohorts by age 45 and subdivided by sex (n): ≤45 (M59, F75), and >45 (M102, F99). #### Summary of Results Young men demonstrated significant depression of their HDL-C compared to women and standard reference values resulting in comparable differences in nonHDL-C and and other lipid values. These gender differences were less apparent in the older cohort as shown in the table. Mean Systolic Blood pressure also differed between genders in the young cohort, though the means were within the standard range of normal. The young cohort did not demonstrate abnormalities or difference in random glucose determinations but this value markedly increased in the older cohort. #### Conclusions Among the components of the metabolic syndrome, marked depression of HDL-C is most readily apparent in young South Asian men. The data infer that HDL-C and elevation of systolic blood pressure may be early predictors of the development of metabolic syndrome and may be playing a more causal role than hyperglycemia in the pathogenesis of premature atherosclerosis. Alternatively, HDL-C and sBP are more readily affected by the molecular causes of the metabolic syndrome. View this table: [Table13](/content/57/1/301/T13) ### 99 NONINSULINOMA PANCREATOGENOUS HYPERINSULINEMIC HYPOGLYCEMIA SYNDROME IN AN 18 YEAR OLD POST GASTRIC BYPASS SURGERY S. Patel1, C. Koch1, S. Asnani2 * 1University of Mississippi Medical Center, Jackson, MS and 2Jersey Shore University Medical Center, Neptune, NJ*. #### Case Report Background: The pandemic of obesity includes teenagers and the pediatric age group as well. Behavioral modification and pharmacotherapy produces modest long term benefits. Gastric bypass surgery is emerging as an alternative treatment for weight loss. Rapid weight loss post gastric bypass surgery has been associated with noninsulinoma pancreatogenous hyperinsulinemic hypoglycemia syndrome due to neo-differentiation of islets of Langerhans. Objective: To illustrate a potentially deadly side effect, hypoglycemia resulting from nesidioblastosis, of/after gastric bypass surgery in an 18-yo obese girl. Case Report: An 18-yo girl with recurrent symptoms of postprandial neuroglycopenia, which could not be controlled with lifestyle modifications. She had history of morbid obesity status post Roux-en-Y gastric bypass surgery and 160 lbs weight loss in 10 months (BMI 48 to 24 kg/m2). After non diagnostic 72 hr fast results, she underwent a mixed meal study with a nadir glucose of 30 mg/dL at 120 min associated with neuroglycopenic symptoms. Concomitant serum insulin was 11 uU/ml and C-peptide 4.3 ng/mL. Helical CT abdomen showed no pancreatic mass. A calcium stimulation test suggested abnormality in splenic artery distribution. She underwent distal pancreatectomy & splenectomy with successful resolution of her hypoglycemic symptoms. Path results confirmed nesidioblastosis showing islet cell hypertrophy. Discussion: To our knowledge, we present here the youngest case of gastric bypass surgery associated with nesidioblastosis. Altered GI transit stimulates gut hormones, notably GLP-1. GLP-1 mediates beta cell neogenesis and proliferation while inhibiting apoptosis. Longterm stimulation of beta cell growth may be involved in the pathogenesis of this disorder. GLP-1 receptor agonist, exenatide, and DPP-IV inhibitor sitagliptin are both approved by the FDA for management of type 2 diabetes. Patients treated with these agents need to be monitored for potential risks of longterm beta cell stimulation which may result in autonomy and inappropriately high insulin levels. Caution is also recommended when treating children with pharmacotherapy and surgery for obesity. ### 100 AN UNUSUAL CAUSE OF HIRSUITISM ASSOCIATED WITH VIRILIZATION CAUSED BY RARE OVARIAN NEOPLASM S. Patel1, A. Mathew2, A. Gandy2, S. Bigler2, C. Koch1, G. Uwaifo1 * 1University of Mississippi Medical Center, Jackson, MS and 2University of Mississippi Medical Center, Jackson, MS.* #### Case Report Background: Hirsutism &/or virilization affects 8-10% of women between age 18-45 y. It is often a source of major psychological discomfort and may be a sign of a medical disorder. While polycystic ovarian syndrome is the commonest single identifiable cause, ovarian neoplasms which contribute to <5% of all cases need to be identified to enable appropriate treatment. Objective: To illustrate that steroid cell ovarian tumors should be considered in the differential diagnosis of hyperandrogenism and virilization. Case Report: A 45 year old African American Female with a 5 month history of male pattern hair growth on face, chest, arms, legs and back; deepening of voice; enlargement of clitoris and dull left lower quadrant abdominal pain, reported amenorrhoe for 15 years. She denied vaginal discharge, frontal balding or acne. Physical exam confirmed male pattern hair growth. Ferriman-Gallwey score was 25 (<8) and clitoral index >35 mm2. Blood work showed a serum testosterone of 282 ng/dl (H), androstenedione 289 ng/dl (H), 17-OH progesterone 450 ng/dl (H), beta-hCG <5 MIU/ml, LDH 317 U/dl, CA-125 11.8 u/ml, alpha fetoprotein 3.0 ng/ml, DHEAS 114 ug/dl, inhibin A 2.9 pg/ml (H), inhibin B <10 pg/ml. Pelvic ultrasound and CT scan of pelvis confirmed a 5.2 cm left ovarian mass. She underwent left salpingo-oophorectomy. Histopathology showed steroid cell tumor consisting of mixed cell types resembling adrenocortical, stromal steroid and Leydig cells with focal areas of hemorrhage. The patient reported improvement in her symptoms as early as 8 weeks postsurgically. F/u hormone levels were: testosterone 16.2 ng/dl, androstenedione 54 ng/dl, 17-OH progesterone 89 ng/dl. Discussion: Steroid cell tumors comprise 0.1% of all ovarian neoplasms. Recurrence rate is 25% within the first five years. Signs of hyperandrogenization regress after surgery. High mitotic figures, marked cell atypia, size >7 cm, and areas of necrosis and presence of Cushing's syndrome are associated with propensity for recurrence. Ovarian tumors need to be considered in the differential diagnoses of hirsutism, especially when associated with virilizing clinical syndromes. ### 101 INSULIN ANALOGS VERSUS HUMAN INSULINS IN THE TREATMENT OF PATIENTS WITH DIABETIC KETOACIDOSIS (DKA) D. Smiley, P. Mulligan, A. Temponi, D. Umpierrez, G. Umpierrez *Emory University SOM, Atlanta, GA.* #### Purpose of Study This study compared the safety and efficacy of insulin analogs and human insulins both during the acute intravenous (IV) treatment phase and during the transition to subcutaneous (SC) insulin for patients with DKA. #### Methods Used In a multicenter, open-label trial, patients with DKA were randomized to receive IV regular or glulisine insulin. After resolution of DKA, patients treated with regular IV were transitioned to NPH and regular SC twice daily (n = 34). Patients treated with glulisine IV were transitioned to glargine once daily and glulisine SC before meals (n = 34). After DKA, both groups were started on a total daily dose (TDD) of 0.6-0.8 U/kg/day. #### Summary of Results Patients were similar in the glulisine and regular groups at admission (BG: 530 ± 30 v. 553 ± 29 mg/dl, pH: 7.19 ± 0.01 v. 7.14 ± 0.03, HCO3: 13 ± 1 v. 12 ± 1 mEq/L, A1c: 11.7 ± 0.4% v. 11.6 ± 0.5% (mean ± SD, *P* = NS). The mean duration of treatment until DKA resolution was similar in the IV regular group (9 ± 5 hrs) and the IV glulisine group (10.5 ± 6 hrs, *P* = NS). There were no differences in the total amount of insulin given or mean duration of insulin infusion between the IV glulisine and IV regular groups. After transition to SC insulin, the mean BG after the first day of therapy was 196 ± 92 mg/dL in the glargine/glulisine and 204 ± 101 mg/dL in the NPH/regular group(*P* = NS). Similarly, there were no differences in the TDD of SC insulin given in the glargine/glulisine group and the NPH/regular group, 60 ± 34 v. 59 ± 12 units, respectively (*P* = NS). Patients treated with NPH/regular insulin, however, had a higher rate of hypoglycemic events (BG <70 mg/dL) than those treated with glargine/glulisine. Fourteen patients (41%) treated with NPH/regular had 25 episodes of hypoglycemia and 5 patients (15%) treated with glargine/glulisine had 6 episodes of hypoglycemia (*P* < 0.01). None of the episodes were associated with loss of consciousness or seizure. #### Conclusions In conclusion, the use of glulisine IV is as safe and effective as regular IV insulin during the acute treatment of DKA. The use of glargine/glulisine following resolution resulted in similar glycemic control but less hypoglycemia compared to the NPH/regular regimen. A basal-bolus insulin ### 102 HIGHLY OXIDIZED, GLYCATED LDL INDUCED APOPTOSIS IN HUMAN RETINAL CAPILLARY PERICYTES: OXIDATIVE STRESS, PROTEASOME INHIBITION AND MITOCHONDRIAL DYSFUNCTION M. Wu1, Y. Chen1, K. Wilson1, M.E. Boulton2, M. Applegate3, J. Ma1, L.I. Szweda3, T.J. Lyons1 * 1University of Oklahoma Health Sciences Center, Oklahoma City, OK; 2University of Florida, Gainesville, FL and 3Oklahoma Medical Research Foundation, Oklahoma City, OK*. #### Purpose of Study Retinal pericyte loss due to apoptosis is thought to play a central role in the development of diabetic retinopathy (DR). Generation of highly oxidized-glycated LDL (HOG-LDL) under hyperglycemia is an important risk factor for the development of DR. Our previous studies have demonstrated that human retinal capillary pericytes (HRCP) exposed to HOG-LDL undergo apoptosis. The purpose of current study is to investigate its potential mechanisms. #### Methods Used In cell culture studies, apoptotic mechanisms regarding oxidative stress, proteasome inhibition and mitochondrial dysfunction were assessed. Immumnostaining of ox-LDL and Bax was performed in human retinal sections from non-diabetic and (Type 2) diabetic with moderate non-proliferative diabetic retinopathy (NPDR). #### Summary of Results The results showed that, in vitro, HRCP exposed to HOG-LDL showed enhanced levels of reactive oxygen species and 3-nitrotyrosine in parallel with a decreased level of glutathione peroxidase-1. In addition, the proteasome, responsible for degrading activated pro-apoptotic Bcl-2 proteins, is inactivated when HRCP are incubated with HOG-LDL. This is accompanied by a decreased cytosolic level of Bax, coinciding with increased cytosolic levels of cytochrome c and apoptosis-inducing factor. In ex-vivo immunohistochemical studies, ox-LDL and Bax were present in the ganglion cell and inner nuclear layers of retina from diabetic subjects with non-proliferative diabetic retinopathy, but are absent in non-diabetic retina. #### Conclusions Based on these considerations, we propose that retinal pericytes exposed to HOG-LDL undergo apoptosis through enhanced oxidative stress, proteasome inhibition, and mitochondrial dysfunction. ## **Gastroenterology and Clinical Nutrition Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 103 BASELINE INDICATORS OF DEATH IN PATIENTS WITH GASTROPARESIS R. Bhakta2, R. Humble2, T. Cutts3, D. Spree1, T.L. Abell1 * 1University of Mississippi Medical Center, Jackson, MS; 2University of Mississippi Medical Center, Jackson, MS and 3University of Tennessee Memphis, Memphis, TN* #### Purpose of Study Gastroparesis, a clinical syndrome associated with nausea/vomiting and disordered gastric emptying, is associated with significant morbidity and mortality. We aimed to examine a large group of GP patients to see what baseline characteristics might be associated with later mortality. #### Methods Used We examined 441 consecutive patients (81 m, 360 f, mean age 43 years, with Dx: 264 ID, 114DM and 63 post-surgical disorder) with GP symptoms seen over a 15 year period. Baseline assessment of patients symptoms by GI Total Symptom Score (Nausea, Vomiting, Early Satiety/Anorexia, Bloating/Diarrhea, and Abdominal Pain as TSS) and quality of life by the IDIOMS tool (a health-related quality of life measurement), physiologic measures of gastric emptying (of a low fat meal) and electrogastrography (cutaneous and mucosal) were all compared to the outcome of survival or death over time. Patients were offered treatment, including drug, device or other therapies, all as standard of care. #### Summary of Results 333 patients had complete data, and over a follow up mean time 52.49 months, 39 patients died. Logistic regression was performed that compared each patient's baseline measure to find a correlation between symptoms, quality of life or physiologic measures, and death. Within the components of the TSS, baseline vomiting had a strong correlation with death (*P* = 0.0333). The odds ratio of death with respect to baseline vomiting was 1.353 and the confidence interval was between 1.024 and 1.788. The baseline IDIOMS score also proved to be a highly significant indicator of death (*P* < 0.001). The odds ratio of death with respect to baseline IDIOMS score was 1.233 and the confidence interval was between 1.130 - 1.346. (See table). #### Conclusions The degree of baseline vomiting and baseline quality of life scores are both reliable indicators of potential death in patients diagnosed with gastroparesis. Gastroparetic patients who have significant baseline vomiting or poor quality of life are a high risk group and may need specific interventions to lower mortality risk. View this table: [Table14](/content/57/1/301/T14) ### 104 DRUG INDUCED CHOLESTASIS TRIGGERED BY QUETIAPINE R.M. Cohen1, J. Scales1, B. Baskovich2, J. Judah1,3, J. Tantravahi1,4 * 1University of Florida, Gainesville, FL; 2University of Florida, Gainesville, FL; 3University of Florida, Gainesville, FL and 4University of Florida, Gainesville, FL*. #### Case Report We report a case of a patient who developed acute cholestasis secondary to three weeks of newly initiated therapy with quetiapine. A 26 year old patient with past medical history significant for schizophrenia and bipolar disorder presented with acute liver failure. His medications included lithium 900 mg three times a day and quetiapine 600 mg each night. Physical examination was notable for frank jaundice, scleral icterus, sublingual jaundice, and right upper quadrant tenderness. The patient developed cholestasis after three weeks of quetiapine. The signs and symptoms as well as laboratory abnormalities resolved after discontinuation of quetiapine and did not recur with follow up of approximately 2 months. Liver biopsy which revealed severe cholestasis with ductular proliferation and pericholangitis consistent with toxic injury as well as the Naranjo probability scale indicated that quetiapine was the probable cause of the cholestasis. In a small subset of patients, quetiapine has been shown to cause asymptomatic increases in liver enzymes, primarily in AST. Subfulminant liver failure from quetiapine has only been described in one case report. In another case report, a 30 year old male patient with schizoaffective disorder and insulin-dependent diabetes developed quetiapine-induced cholestasis after 3 weeks of treatment. His symptoms resolved after discontinuation of quetiapine. There are also case reports of other aytpical antipsychotics causing hepatitis and cholestatic hepatitis. In our patient, symptoms occurred after three weeks on quetiapine and resolved also after withdrawal of quetiapine. The mechanism of liver toxicity with atypical antipsychotics is not known. However, the cholestasis is hypothesized to arise from a hypersensitivity reaction and from the toxicity of metabolites from the offending agent. Since quetiapine-induced cholestasis is a rare occurrence and is usually reversible, starting the medication in those who are likely to benefit from treatment, monitoring of symptoms and laboratory values, and educating the patient of the risks and benefits is a reasonable approach. ### 105 ESOPHAGEAL CARCINOMA PRESENTING WITH POLYMYOSITIS N. Dbouk, I. Obideen, M. Harrison, J. Massaad, K. Obideen, M. Wehbi *Emory University School of Medicine, Atlanta, GA* #### Case Report A 63 year old Caucasian male presented to our medical center complaining of progressive weakness.He reported difficulty rising from a seated position and climbing stairs as well as difficulty combing his hair.Symptoms were also associated with weight loss. On further questioning he also reported difficulty swallowing. Physical exam showed symmetrical weakness involving the proximal muscules in both upper and lower extremities. His lab tests revealed an elevated creatine kinase and LDH. Radiological studies assessing swallowing were consistent with transfer dysphagia. Electromyography (EMG) was consistent with a myopathy. Further work up was consistent with a diagnosis of Polymyositis.An upper endoscopy was performed as part of a work up for underlying malignancy and revealed a 6 cm flat exophytic mass in the distal esophagus. Biopsies were consistent with an adenocarcinoma. It was staged at IIA. The patient was treated with a combination of chemo and radiation therapy and surgery. His muscle weakness subsided completely as the patient recovered. Polymyositis is an idiopathic inflammatory myopathy. Its prevalence is approximately one per 100,000 in the general population with a female to male predominance of about 2:1. The peak incidence occurs between the ages of 40 and 50, but individuals of any age may be affected. Weakness involving the proximal muscules is the most common presenting feature. The onset is usually insidious, with gradual worsening over a period of several months. Diagnosis is usually based on typical presenting features in addition to an elevated creatine kinase, abnormal EMG, the presence of myositis specific antibodies, and a muscle biopsy. Polymyositis can present as a paraneoplastic syndrome. Cancer of the cervix, lungs, ovaries, pancreas, bladder, and stomach account for the majority of cancers associated with inflammatory myopathies. Esophageal cancer is very rarely associated with Polymyositis. Dysphagia in Polymyositis is often attributed to muscle weakness rather than an obstructing mass. This can lead to a delay in diagnossi of potential underlying esophageal cancer. In conclusion, esophageal cancer should be considered in the differential diagnosis in patients presenting with Polymyositis as early diagnosis can result in better survival. ### 106 ATYPICAL GASTROINTESTINAL PRESENTATION OF T CELL LYMPHOMA E. Gupta, J.E. Rose, K. Olden *University of Arkansas for Medical Sciences, Little Rock, AR* #### Case Report Introduction- Liver involvement is commonly seen in disseminated non-Hodgkin's Lymphoma, however, it is rarely the presenting organ. Here we describe a case of disseminated non-Hodgkin's lymphoma presenting as acute hepato-biliary disease. Case- 47 year old male with history of cirrhosis (etiology undetermined), diabetes mellitus and pancytopenia was admitted to ICU for hypotension and failure to thrive. He had icterus, minimal ascitis and hepato-splenomegaly on physical examination. No lymphadenopathy was noted. Laboratory workup on admission showed elevated total bilirubin (10.1 mg/dl) and liver enzymes. Serology for acute hepatitis, HIV, EBV and autoimmune hepatitis was negative. CT abdomen showed cirrhotic liver with heterogeneous arterial enhancement of the liver without definite mass lesions. Hospital course was complicated by progressively worsening hypotension, respiratory failure, profound acidosis, disseminated intravascular coagulation and multi-organ system failure leading to death on hospital day 12. Autopsy of the liver showed cirrhotic changes with infiltration with atypical small lymphocytes confined to septa which were CD3 and CD5 positive(CD4-weakly positive; CD8, CD20, CD57, CD56, CD30, Alk-1, granzyme B, TIA1 and S100-negative). Discussion- Unusual clinical/ histological features include-1) An initial clinical presentation of hepatic dysfunction without obvious physical signs of lymphoma; 2) An aggressive nature of disease; 3) Liver biopsy with infiltration confined to septa and 4) Involvement of the entire liver, observed as heterogeneous enhancement of liver without any focal mass lesion as seen on CT scan. Initial diagnosis was challenging due to unusual clinical presentation suggesting inflammatory hepato-biliary disease and the absence of enlarged lymph nodes. Conclusion: Early suspicion of this aggressive lymphoma is important and should be considered in the evaluation of a patient whose course is atypical for hepatitis. Even in the absence of a mass lesion or lymphadenopathy, peripheral T cell Lymphoma should be included in the differential diagnosis of acute hepatic dysfunction in a patient who has no evidence of viral, toxic, autoimmune or metabolic liver disease. ### 107 POST-FUNDOPLICATION ACHALASIA, A CASE SERIES R.A. Hejazi, S. Sostarich, R.W. McCallum *Kansas University Medical Center, Kansas City, KS* #### Purpose of Study Nissen fundoplication is an effective surgical treatment for refractory gastroesophageal reflux disease (GERD). One of the long term complications, dysphagia and post fundoplication achalasia are illustrated by a series of cases. #### Methods Used In a retrospective study from September 2007 to June 2008 we reviewed all the patients that presented new onset dysphagia following a fundoplication surgery performed at our medical center. Chart review was used to collect the data. The diagnosis of post-fundoplication achalasia (PFA) was based on a history of dysphagia after fundoplication surgery supplemented by EGD including esophageal biopsy to rule out eosinophilic esophagitis, barium swallow with 13 mm tablet challenge and HRM and/ or conventional perfusion manometry. #### Summary of Results 5 patients were identified with PFA in our institution. Tables 1 & 2 summarize the demographic and clinical characteristics. 3/5 required repeated balloon dilatations with a mean of 1.8 times. The mean delay between surgery and the onset of achalasia symptoms was 1 year. In all fundoplication was performed due to severe GERD refractory to medical treatment. No patient had dysphagia before fundoplication. One patient underwent surgery involving a "Heller" myotomy and reconstruction of a loose fundoplication to address the dysphagia symptoms. In all EGD with biopsy were normal. #### Conclusions Post-fundoplication achalasia is a complication occurring after fundoplication surgery and its symptom onset can be delayed. Repeat pneumatic dilatation can be helpful although surgery also be needed. We hypothesize that a sclerosing and/ or fibrosing lesion is now more likely than inflammatory stenosis. View this table: [Table15](/content/57/1/301/T15) Demographic and clinical characteristics. View this table: [Table16](/content/57/1/301/T16) Manometric and radiologic characteristics. ### 108 GASTROINTESTINAL HISTOPLASMOSIS PRESENTING AS BOWEL PERFORATION IN A PATIENT WITH HIV/AIDS D. Kadaria1, H. Alshayeb1, W. Chishti2, S. Sinclair2 * 1UTMEM, Memphis, TN and 2UTMEM, Memphis, TN* #### Case Report Gastrointestinal histoplasmosis is recognized clinically in less than 10% of cases, however, 70% of patients with disseminated histoplasmosis have gastrointestinal involvement at autopsy. Lesions most often involve the colon or ileum, especially the ileocecal area, but may occur from the mouth to the anus. Misdiagnosis of colitis or colon cancer of the associated bowel ulcers and polypoid masses is not uncommon. Few case reports of bowel perforation as a complication of disseminated histoplasmosis have been described. This report presents a patient with AIDS (CD4 count:24) who presented with abdominal pain and constipation. Abdominal radiograph showed small bowel obstruction with pneumoperitoneum. Exploratory laparotomy revealed terminal ileum perforation. Pathology showed histoplasmosis. A 42-year-old man with PMH of AIDS (CD4 count:24) presented with fever, weight loss, oral thrush, nausea, vomiting, abdominal pain and constipation for one week. Temperature: 37C, BP: 110/70, HR: 110. PE revealed oral thrush, no palpable lymphadenopathy, chest and cardiac exams were normal, abdominal exam revealed generalized tenderness with rebound tenderness, no guarding, bowel sounds were hypoactive. Laboratory revealed a WBC: 3.1 Hct: 22, Plt: 115. Cr: 2.2 (baseline: 1.2), Na +: 131, K +: 3.5, Cl-: 96, Mg2 +, Ca2 +, PO4 were normal, HCO3: 20. LDH: 320, lactic acid: 2.6 mg/dl, Albumin: 3 mg/dl, LFT was normal. Urinalysis was clean, buffy coat film was negative for organisms. Abdominal radiographs showed small bowel obstruction with pneumoperitoneum. Exploratory laparotomy showed perforated terminal ileum. Pathological exam revealed histoplasmosis. Bacterial and fungal blood cultures were subsequently positive for Histoplasma capsulatum and urine histoplasma antigen was positive. Course was complicated by septic shock with acute renal failure that responded to volume resuscitation, vasopressors, steroids, mechanical ventilation and treatment with amphotericin B. The patient's condition improved with resolution of shock and extubation. However, one week later he aspirated resulting in acute respiratory failure and prolonged fruitless cardiac arrest. #### Conclusion We report a case of disseminated histoplasmosis presenting with bowel perforation. ### 109 ENDOSCOPIC RESECTION OF GRANULAR CELL TUMOR OF THE ESOPHAGUS PRESENTING WITH DYSPHAGIA AND ODYNOPHAGIA: A CASE REPORT S. Ngamruengphong, A. Rakvit, S. Parupudi *Texas Tech University Health Science center, Lubbock, TX* #### Case Report A 46-year-old woman presented with progressive dysphagia to solids and odynophagia. She denied heartburn, nausea and vomiting. Upper Endoscopy revealed a small 5 mm submucosal mass at the distal esophagus. Endoscopic Ultrasound (EUS) revealed a corresponding hypoechoic mass with well-defined border arising from deep mucosa (Layer 2). Endoscopic mucosal resection (EMR) of lesion was performed using snare after submucosal saline and epinephrine injection. Histopathology showed a benign neoplasm composed predominantly of cells with spindle-shaped nuclei and round nuclei with granular eosinophilic cytoplasm. Immunohistochemistry was stained positive for S100 and negative for smooth muscle actin, CD34 and CD117. This is consistent with a granular cell tumor. Patient's symptoms of dysphagia and odynophagia were completely resolved at 3 months follow up. This is an unusual case of granular cell tumor of esophagus presenting with dysphagia and odynophagia. It is an uncommon tumor found in the esophagus. Patients are usually asymptomatic and the lesion are found incidentally. There are case reports of symptomatic large lesions which are recommended to be removed surgically. We used EUS to determine the original layer of this mass and performed endoscopic mucosal resection with snare using saline and epinephrine assisted technique. Use of EUS and EMR has not been reported in the context of granular cell tumors to the best of our knowledge. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F5.medium.gif) [Figure.](/content/57/1/301/F5) Figure.   ### 110 A RARE PRESENTATION OF PROSTATE CANCER METASTATIC TO THE STOMACH S.S. Sakaria1, D. Patel1, M. Wehbi2, A. Osunkoya2, K. Obideen2 * 1Emory University, Decatur, GA and 2Atlanta VA Medical Center, Atanta, GA*. #### Case Report ABSTRACT An 84 year-old male with a history of prostate cancer presents with intermittent melena.Physical exam was unremarkable. Laboratory results revealed a hemoglobin of 6.5 g/dL and hematocrit of 19.4 g/dL. An EGD showed a large, 5 cm, ulcerated mass along the greater curvature of the stomach (Fig. 1).Pathological examination of biopsies taken from the mass demonstrated prostatic adenocarcinoma with tumor cells staining positive (brown) for PSA (Fig. 2) and PSAP. The above case demonstrates an extremely rare presentation of metastatic prostate cancer. A review of the literature identified only two previously reported cases of endoscopically diagnosed prostate cancer metastatic to the stomach. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F6.medium.gif) [Figure.](/content/57/1/301/F6) Figure.   ### 111 IS THERE A CORRELATION BETWEEN HBA1C LEVELS AND GASTRIC EMPTYING TEST (GET) RESULTS IN DIABETICS PRESENTING WITH GASTROPARESIS AND DYSPEPSIA SYMPTOMS? I. Sarosiek1, R. Hejazi1, K. Roeser1, J. Forester2, J. Sarosiek1, R.W. McCallum1 * 1Kansas University Medical Center, Kansas City, KS and 2Kansas University Medical Center, Kansas City, KS*. #### Purpose of Study Gastroparesis (GP) is a serious GI complication affecting up to 50% of type I and 20% of type II diabetics (DMs). It still remains a clinical challenge to find reliable diagnostic tests and possible predictors for both diagnosis and treatment of this condition. Therefore, the aim of the study was to investigate whether a correlation exists between GET results at 2 and 4 h and HbA1c levels in diabetics presenting with symptoms of dyspepsia/gastroparesis. #### Methods Used 143 DM patients (97F, mean age 39 (21-65) with severe GP as determined by their need for implantation of a gastric neurostimulator (GES) (Enterra System) had documented delayed GET. 22 additional DM patients, (17 F) mean age 44 (29-63) were referred to our site for evaluation of dyspepsia symptoms. They did not meet criteria for GES therapy. All of the diabetics underwent the same 4 hour standardized GET scintigraphic test with low fat EggBeater meal (normal values <60% at 2 hrs and <10% at 4 hrs). HbA1c level was obtained at or close to the GET test. Mean values with ± SD and Pearson Correlation test was utilized in this study. #### Summary of Results In diabetics diagnosed with severe, drug refractory gastroparesis mean value of HbA1c was 8.7% (range 5-16.4) versus 8.5% (range 5.8-11.7) in the dyspepsia and mild GP with dyspepsia group. The mean retention of the radiolabeled test meal was 69% (±20.4) at 2 and 44% (±26.4) at 4 h in the severe GP population of diabetics versus 50% (±19.2) at 2 h and 15% (±22.5) at 4 h in the dyspeptic patients. There was no significant correlation between HbA1c and % of retained food at 2 and 4 h after ingestion of the isotope labeled meal in the 2 groups of diabetics (p>0.050). #### Conclusions 1. Mean HbA1c level was similar in diabetics with both severe and mild gastroparesis or with dyspepsia and normal gastric emptying. 2. The HbA1c does not predict the gastric emptying results in diabetics undergoing assessment for dyspepsia symptoms and it is not a marker for gastroparesis ### 112 IS IT CHRONIC INFLAMMATORY BOWEL DISEASE OR CHRONIC INFECTIOUS COLITIS? Al Shabaneh, H. Tamimi *Texas Tech University HSC, Lubbock, TX*. #### Purpose of Study Differentiating inflammatory bowel disease (IBD)from chronic infectious colitis is a diagnostic and a therapeutic challenge. The features of colitis related to campylobacter on endoscopy is difficult to distinguish from a number of other colonic mucosal diseases such as antibiotic associated colitis, amebiasis, shigellosis, salmonellosis, invasive E-coli colitis and ischemic colitis(1). On pathology, acute and chronic colitis, cryptitis, crypt abscesses and mucus depletion are not specific to IBD and data are needed to exclude another nongranulomatous inflammatory etiologies of chronic colitis(1). A 31 year old male with history of hypertension, diabetes mellitus, hyperlipidemia was referred for colonoscopic evaluation of a 6-week history of bloody diarrhea, lower abdominal cramps, weight loss, anorexia and arthralgias. Has no family history of IBD. The patient came in contact with puppies one week prior to onset of his symptoms. His physical examination showed an obese afebrile male with tenderness in both lower abdominal quadrants and lower limbs varicose veins. His CBC and comprehensive metabolic profile were normal. Colonoscopy showed diffusely erythematous, friable, eroded, granular mucosa suggestive of pancolitis (see figure 1) with the same findings in the terminal ileum. A large cratered ulcer was found on the ileocecal valve. Stool was collected during colonoscopy and random colonic biopsies were obtained. #### Conclusions Figure 1 The colon biopsies showed a benign ileocecal valve ulcer, lymphocytic and plasmacytic infiltration in the lamina propria with crypt abscesses suggestive of inflammatory bowel disease. The stool culture came back positive for + 4 campylobacter jejuni microorganisms. The patient was treated with erythromycin. Symptoms completely resolved in one week. Campylobacter induced diarrheal illnesses are usually self limiting with a seven day illness in the majority of the cases (2). Only 10-20% have an illness lasting more than a week(2).This chronic form is rare and very few case reports have been published in the literature describing this rare form of the disease. It is critical to distinguish this infection from inflammatory bowel disease given the therapeutic implications and to avoid the potentially lethal complications (2). ## **Health Care Research Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 113 MOST FREQUENT AMBULATORY CARE SENSITIVE CONDITIONS AMONG PATIENTS ADMITTED TO THE USA MEDICAL CENTER, 2004-2007 A.L. Broadnax2,3, F.A. Mohammed3, R.D. Foreman3, M.I. Arrieta1,3 * 1University of South Alabama, Mobile, AL; 2Mobile, AL and 3University of South Alabama, Mobile, AL* #### Purpose of Study Ambulatory Care Sensitive Conditions (ACSC) are conditions for which potentially fatal disease complications and hospitalization can be prevented by adequate primary care. Factors that have been associated with hospitalization for ACSC include income, race, education, access to primary care services, and insurance coverage. Hospitalizations for ACSC can be used to evaluate the status of primary healthcare of the community by indicating areas with poor access to healthcare. We studied the rates of hospitalization for ACSC over four years (2004-2007) at the University of South Alabama Medical Center (USAMC), a tertiary care teaching hospital in Mobile, AL. We hypothesized that there would be little change in ACSC diagnoses throughout the four year period. #### Methods Used USAMC discharge records were sorted and analyzed using the Statistical Analysis Software program. Data collected included demographics, risk of mortality, ICU days, length of hospital stay, and charges. #### Summary of Results The most frequent ACSC are congestive heart failure (CHF) (26%-36%), bacterial pneumonia (18%-23%) and uncontrolled diabetes (18%-22%). The majority of patients admitted for these ACSC reside in the immediate service area of USAMC, a predominantly African American, low income, medically underserved area. In fact, 82% to 93% of patients admitted for diabetes or pneumonia were African American. 10-20% of patients admitted for any of the three most frequent ACSC were considered to be at high or extreme risk of mortality. 30% of patients admitted for diabetes were admitted to intensive care. One-third of patients with ACSC were charged up to $5,000, another third $5,000 to $10,000; and the final third charged over $10,000. #### Conclusions Results show that there is a slight decreasing trend in admissions for CHF and diabetes over the four years, and a slight increase in admissions for pneumonia. Further study is required to understand the relationship between the downward trends observed and access to primary care, particularly because those could be explained by a concurrent downward trend (estimated 8.6% decrease)in the population living in USAMC service area. ### 114 THE ECOLOGY OF INTRAVENOUS ACCESS IN CHILDREN P.M. Darden, E.S. O'Brien, K.E. Chamberlain, K.D. Freeland *Med Univ of SC, Charleston, SC* #### Purpose of Study Intravenous access (IV) in children is a common and often difficult procedure that is not well studied. How commonly are IVs used in hospitalized children and are there predictors of need to start a new IV? #### Methods Used A cross-sectional survey of admitted patients on the pediatric medical/surgical wards of a children's hospital. The medical records of all patients admitted to the wards based on a 7AM census report were reviewed. On days surveyed all non ICU and non neonatal beds were included. Surveys were done on weekdays and all patients would be included on each day a survey was performed. Data abstracted included demographics, IV presence, IV type, and new IV start. #### Summary of Results There are 4 wards and 72 beds. During April and May of 2008, surveys were performed on 26 days and included 1,352 patients. The median age was 4 years (0-17), 28% had been admitted in the last 24 hours. In the past 24 hours 82% (1102) had an IV with 94% of those had an IV at the end of the day with 12% started or restarted in the past 24 hrs. Of those with an IV, 11% were central lines, 81% were peripheral lines. Those with IVs in the last 24 hours were older than those no IVs (6.7 v. 3.0 yrs, *P* <.01). Children with central lines were older than those with peripheral IVs (10.3 v. 6.3 yrs, *P* <.01). In a logistic model of age, unit, gender and race were used to predict an IV in the last 24 hours, older age (OR for each year 1.09, 1.04-1.13) and ward (subspecialty v. general, OR 9.31, 4.40-19.7) independently predicted increased odds of an IV. In a model controlling for age, admission, unit, gender, race and type of IV and predicting starting or restarting an IV in the last 24 hrs found that being admitted in the last 24 hours (OR 1.54, 1.05-2.27) and type of IV (PIV v. Central, OR 10.7 v. 2.6) were associated with an IV start. #### Conclusions IVs were used in almost all children in this children's hospital. Our findings of having an IV and needing an IV started should provide guidance in staffing and care of hospitalized children. ### 115 ACADEMIC DEPARTMENT OF PEDIATRICS AS HEAD START (HS) GRANTEE- 10 YEAR EXPERIENCE C.R. Field *University of Arkansas for Medical Sciences, Little Rock, AR* #### Purpose of Study Review the 10 year experience of an academic health center Department of Pediatrics as local HS program grantee. #### Methods Used Nationwide, 1604 HS programs serve 908,000 pregnant women and children 0- 5 y/o, total funding $6.87B. HS income eligibility is 100% of poverty level or less (2008- $21,200/ family of 4), 60% HS children are non-white. Only two academic health centers serve as local HS grantees- UAMS Head Start Programs, and Project Eagle- University of Kansas Medical Center. UAMS HS program maintains database (ChildPlus) and reports to HS Bureau. #### Summary of Results Since 1998 the UAMS HS programs provided 400 child/year services to pregnant women and children 0-2y/o, and 10,000 child/year services to children 3-4y/o, 15% with a diagnosed special need. Services include screens for health, dental, nutrition, mental health, and services as needed. Current funded enrollment is 1080- 7% white, 23% Hispanic, 70% African American. Ten year totals for direct funding for operations: HS Bureau $55M and USDA $5M. The program serves as community service-learning site: early childhood education undergraduates, MBA interns, social work students, and Child Development Associate students. The program serves as a service learning site for the academic health center: undergraduate and graduate/APN nursing students, pharmacy students, optometric technician students, medical students, dental hygeine students, nutrition graduate students, dietician interns, and MPH students. Funded grants targeting the program and population include AHRQ, SAMSHA, AR Department of Health, SBC Foundation, General Mills Foundation totaling $2.3M. Publication topics/ academic presentations utilizing the HS population include: service learning, asthma, and parenting #### Conclusions Academic health centers can be a good fit for a Head Start program. HS programs serve as sites for education, service, research, -the pillars of academic medicine. HS Programs are ideally suited as community-based service learning sites. HS Programs are ideally suited as sites for community-based initiatves for underserved populations. ### 116 HOSPITALIZATIONS FOR AMBULATORY CARE SENSITIVE CONDITIONS AT THE UNIVERSITY OF SOUTH ALABAMA MEDICAL CENTER, 2004-2007 A. Gulati1, F.A. Mohammed1, M.I. Arrieta1,2, * 1University of South Alabama, Mobile, AL and 2University of South Alabama, Mobile, AL*. #### Purpose of Study Ambulatory Care Sensitive Conditions (ACSC) are conditions susceptible to management in the outpatient setting. Hospitalizations for ACSC suggest lack of primary care and constitute a valid indicator of a region's access to healthcare. The University of South Alabama Medical Center (USAMC) is a 130-bed tertiary care teaching hospital located in the inner core of the city of Mobile. The USAMC immediate service area hosts a disadvantaged population of 126,130 individuals with 31% living below the poverty line. We evaluated the profile of patients admitted to USAMC for ACSC from the immediate service area in order to determine expenses to the patients and to the system, which represent the cost of these patients not accessing primary care. #### Methods Used This is a cross-sectional survey of hospital admissions for ACSCs at USAMC between January 1, 2004 and December 31, 2007. Computerized discharge records were used to identify hospitalizations for ACSC and details of hospitalizations with regards to length of hospital stay, days in the Intensive Care Unit (ICU) and charges incurred. #### Summary of Results Over the study period, 1,880 patients (2,803 hospitalizations) were admitted with an ACSC diagnosis; 58% of those patients (n = 1,093, 51% Male and 89% African American) were residents of USAMC immediate service area, for a total of 1,744 ACSC hospitalizations. Congestive heart failure, diabetes and bacterial pneumonia were the most frequent diagnoses (33%, 21% and 19%, respectively). Overall, immediate service area patients spent 1,088 days in the ICU, a total of 6,876 days in the hospital, and incurred $19,561,686 in charges. While 34% of patients in the immediate service area were uninsured at the time of hospitalization, 32% had Medicaid and 25% had Medicare, which suggests inadequate use of primary care services even among individuals with health insurance. #### Conclusions Hospitalizations for ACSC represent a high cost in days of productive life lost and charges to patients. Efforts aimed at promoting and facilitating the utilization of primary care services in this disadvantaged population would result in substantial savings to the patient and the health care system. ### 117 PRENATAL CARE UTILIZATION IN RURAL ECUADOR N.L. Jones, R.D. Smalligan *East Tennessee State University, Johnson City, TN*. #### Purpose of Study Research has shown that prenatal visits are a cost effective way of decreasing adverse perinatal outcomes. Despite prenatal care being offered free of charge to Ecuadorian women, it is underutilized. This study sought factors associated with low use of prenatal care. #### Methods Used A 10% random sample of charts of women delivering at 2 hospitals in central Ecuador between Jan-Jun 2006 were reviewed for prenatal information. The adequacy of care was determined based on WHO guidelines and the data correlated with sociodemographic information using the ANOVA statistical method. #### Summary of Results 172 records were reviewed including 119 vaginal deliveries, 25 cesareans, and 26 cases resulting in fetal demise. The age range of pregnant women was 14 to 44yo; 21% under 20, 59% 20-30, 15% 31-40, and 5% over 40. Fifty-two percent were married, 38% had less than 12y of school, 35% were primigravidas and 16% had a prior fetal demise. Prenatal care was inadequate in 71% of women with 37% having none (mean 2.7 ± 3 visits, range 0-11 visits). A negative correlation was found between number of prenatal visits and prior fetal demise (*P* = 0.006), with averages of 1.7 and 3.0 visits for women with and without prior fetal demise respectively. The number of prenatal visits did correlate with better outcomes since those without fetal demise had 3.2 visits on average compared with 0.5 visits for those with fetal loss (*P* < 0.001). No significant correlation was noted between number of visits and age, education, marital status, or number of previous pregnancies. #### Conclusions This study showed an association between lower use of prenatal care and later fetal demise, consistent with other research. The negative association found between prior fetal demise and number of visits contrasts with positive associations found in other studies. Also, where past research found associations between low utilization of care and age, education, marital status, and previous pregnancies, no association was found in our study. Economic and transportation difficulties are known risk factors for poor prenatal care usage and our population's homogenous poverty status likely contributed to our low usage rates. Observation at the hospitals revealed a bias against indigenous women as they were treated poorly and experienced longer waiting times compared with mestizo women, which likely also contributed to inadequate utilization. ### 118 CLINICAL AND MEDICAL COST OUTCOMES OF DIABETES EDUCATION SERVICE IN SPECIALIZED COMMUNITY PHARMACY S.M. Rashed1,2, S. Goldstien3, J. Wang2 * 1University of Tennessee, Health Science Center, Memphis, TN; 2University of Tennessee, Health Science Center, Memphis, TN and 3Self-insured employer, Memphis, TN*. #### Purpose of Study Diabetes Mellitus is a chronic metabolic disease with multiple complications pausing a progressive health and economic burden. The aim of this retrospective Pilot-study was to investigate clinical outcomes and medical costs resulting from a comprehensive diabetes education and management service in specialized community pharmacy. #### Methods Used Diabetes education and management service was offered to patients enrolled in a Self-insured-health-plan. A community based clinical Pharmacist provided one-on-one comprehensive educational sessions. Data was collected from 22 patients with a primary initial diagnosis of diabetes type II. Outcomes measures included clinical data along with total medical and prescription claims data before and during intervention period of complete three years. #### Summary of Results Mean A1c was decreased from 8.9% + 2.2 to 7.0% + 0.9 (2% decrease *P* < 0.001). Improvement in lipid profile was observed from base line; mean + SD triglyceride level reduction 53 + 78 mg/dl (*P* = 0.002), mean + SD HDL level increased 7 + 6mg/dl (*P* = 0.020), However, total-cholesterol and LDL levels reduced with *P* = 0.243 and *P* = 0.220 respectively). Mean year incidence of infection was decreased 1.1 incident/year (*P* = 0.057). Total patient medical costs was decreased by 55%, 45% and 41% compared to baseline during first, second and third year, respectively with a significant decrease in physician office visits. The overall medication costs increased over years with increase in diabetes and hypertension medications. #### Conclusions Comprehensive diabetes education and management in a specialized community pharmacy resulted in improved clinical outcomes with an overall decrease in medical costs. Future plan to test the hypothesis in a formal randomized control study will be arranged. ### 119 IMMUNIZATION PROCEDURES IN PEDIATRIC PRACTICES: A STUDY FROM THE SOUTH CAROLINA PEDIATRIC PRACTICE RESEARCH NETWORK (SCPPRN) J.R. Roberts, K.D. Freeland, J.T. McElligot, E. O'brien, P.M. Darden *Medical University of South Carolina, Charleston, SC*. #### Purpose of Study Assessing the process of immunization administration in pediatric practices is necessary in order to identify ways to improve quality in the delivery of care. The purpose of this study is to evaluate pediatric practices' ability to track their patients' need for, and deliver immunizations. We will also validate their responses as part of a quality improvement initiative. #### Methods Used We surveyed pediatric practices about their current immunization procedures. The surveys consisted of 20 'yes/no' questions and included categories of immunization assessment, medical record keeping, opportunities for immunization administration, and prompting of both providers and patients. Subsequently, we visited practices to directly observe their immunization delivery process and review their charts to validate survey answers. #### Summary of Results Two of the 6 participating practices reported that they assess immunizations rates annually and provided feedback to clinicians. All reported that they have a consistently available vaccine supply, that immunization records were available in 1 easy to locate place in the medical record, and that they immunize at sick visits. All providers reported they were prompted to give immunizations at well visits. Five reported sending reminders of upcoming visits (phone or mail). Three of the 6 practices reported having standing orders for routine immunizations. No practice has a recall system in place when children are overdue for immunizations. After initial on-site observation in the practices, only 1 practice in fact has a single place in the medical record where shots are recorded. Only 2 practices used some type of a prompt for immunizing at sick visits. Upon record review, the frequency of missed opportunities for providing immunizations at sick visits ranged from18%-64%. #### Conclusions Providers' report of immunization delivery processes do not always agree with direct observation. When immunization delivery is suboptimal, verification of processes are necessary to identify opportunities for improvement. Clear and concise record keeping is necessary to improve immunization delivery. ### 120 EFFICIENT USE OF PEDIATRIC EMERGENCY ROOMS K. Sudheimer, S. Shah, J. Roberts *Medical University of South Carolina, Charleston, SC*. #### Purpose of Study The pediatric emergency room at the Medical University of South Carolina has recently seen an increase in non-urgent visits. We developed a survey to assess parents' perceptions on degree of illness in our community and identify reasons why parents chose to bring their children to the emergency room instead of their primary care physician. #### Methods Used This study was conducted in the pediatric emergency room at the Medical University of South Carolina. We asked parents to fill out a survey if their child was triaged as a non-emergent visit by emergency room nurses. The survey had 10 questions including demographic information, reasons for coming to the emergency room and perception on degree of illness. Surveys were collected prior to the child leaving the emergency room. Data were entered into SPSS for analysis. #### Summary of Results A total of 72 surveys were collected from parents out of 75 surveys distributed. We found that 54% of parents brought their child to the emergency room for perceived urgency ("had to be seen tonight"), 14% for no appointments available at primary care physician today and 11% for faster to get in to see doctor. The percentage of parents who brought their child to the emergency room and described their child as being somewhat sick or not sick at all was 58% compared to 39% for this is an emergency or very sick. Fifty-two percent of parents with a high school education or less brought their child to the emergency room for issues they described as only somewhat sick or not very sick compared to 48% of parents with a high school education or greater. #### Conclusions Parents who bring their children to the emergency room perceive their child has a medical problem that requires them to be seen urgently. Socioeconomic characteristics also influence parents' perception on degree of illness. Identifying community attributes can help allocate medical resources to the most efficient system. ## **Hematology and Oncology Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 121 CLINICAL MANIFESTATIONS OF A PANCOAST TUMOR S.J. Ayirookuzhi, G.M. Mills *LSUHSC, Shreveport, LA* #### Purpose of Study Description of an unusual case of Pancoast tumor with a secondary malignancy #### Methods Used Case Report A 51-year old man with a past medical history of 50-pack year tobacco abuse presented with complaints of left shoulder pain of 7 months duration that he described as "laying on a golf ball". Two days before admission he noticed weakness of left upper extremity in all muscle groups below the shoulder as well as droopiness of the right side of face. He also added that he had a 30-pound weight loss for about 3 months before admission. He denied chest pain, shortness of breath, cough, fevers, chills, sweats or trauma. He denied tremor, ataxia, diplopia, dizzness or lightheadedness. He did report increasing clumsiness with fine motor movements of his left upper extremity since two days prior to admission. The rest of his history including past medical, surgical, family and social history were unremarkable. He did not have any allergies and was not on any medications prior to admission. Assessment On physical examination, vital signs were within normal limits. The patient was thin but not cachetic. His cardiac, pulmonary and abdominal exams were unremarkable. He had ptosis and miosis of the left eye (Figure 1) and prominence of the left supraclavicular fossa compared to the right (Figure 2). In addition, there was lower motor neuron facial nerve paralysis of the right side and vasomotor changes of the left upper extremity, notably coolness and a bluish discoloration compared to the opposite side (Figure 3). Anhidrosis was not appreciated. Laboratory testing for routine blood counts and chemistries was unremarkable. A CT scan of the chest confirmed superior sulcus tumor on the left side (Figure 4), also noted on PET imaging. In addition during hospitalization, the patient was found to have a renal mass on the left side. Biopsy of a lytic lesion on the right iliac crest confirmed metastatic renal cell carcinoma in addition to the Pancoast tumor. An MRI confirmed lesions consistent with metastasis to the pons that would explain the right sided lower motor neuron facial nerve paralysis. #### Summary of Results Patient with Pancoast tumor presented with two different malignancies #### Conclusions Pancoast tumor may present with unusual but well described clincal features ### 122 UNUSUAL PRESENTATION OF NEUROBLASTOMA IN THE VAGINAL WALL IN A 2 YEAR OLD CHILD R. Bamba1, E. Manci2, T. Standley3, A. Rao1 * 1University of South Alabama, Mobile, AL; 2University of South Alabama, Mobile, AL and 3University of South Alabama, Mobile, AL*. #### Case Report Introduction: Neuroblastomas are the most common extracranial solid tumors in infancy and the fourth most common malignancy in childhood. Tumors typically occur in the abdominal cavity but unusual sites, such as the orbit, skin, ovary, and urinary bladder, have been reported. They may metastasize to bone, bone marrow, liver or lungs. We report an unusual case of neuroblastoma in a 2-year-old female who presented with vaginal bleeding. The novelty of our case is the site of origin of the tumor, the vaginal wall. Case Presentation: A two year old child presented with vaginal bleeding and was evaluated for trauma and physical abuse. Radiologic scans revealed a mass behind the urinary bladder at the junction of the lower uterine segment and proximal vagina measuring 4.5 cm × 4.3 cm × 4.1 cm. Both ovaries were normal. MRI confirmed that the mass involved her uterus and extended inferiorly to the vagina with extension into the right ischiorectal fossa. Transvaginal biopsy revealed neuroblastoma. MYCN showed amplification at a high level. Staging showed bone marrow metastasis. Urinary VMA, HVA and catecholamines were normal. MIBG showed increase uptake in the region of the retrovesicular space where the mass was seen. She was classified as high risk neuroblastoma, stage 4, with MYCN amplification and treated with chemotherapy as per COG protocol ANBL02P1. She was reevaluated after induction chemotherapy with scans that showed remarkable response to therapy. She underwent vaginoscopy with biopsy of the vaginal wall and no disease could be visualized during surgery. Biopsies showed reactive inflammatory infiltrates and no malignancy. Peritoneal washings were positive for neuroblastoma cells suggestive of microscopic residual disease. Bone marrow was devoid of neuroblastoma. Conclusion: Vaginal primary neuroblastoma is rare since vaginal masses typically suggest rhabdomyosarcoma. Biopsy of this mass and immunohistochemical staining confirmed undifferentiated neuroblastoma. This is the first report of a vaginal neuroblastoma in the pediatric age group. Our case highlights that neuroblastoma is a reasonable differential in the evaluation of vaginal masses in children. ### 123 MALIGNANT TRANSFORMATION OF A DERMOID CYST OF THE OVARY: A CASE REPORT AND REVIEW OF THE LITERATURE S. Bostick, S. Elkins, B. Craft *University of Mississippi Medical Center, Jackson, MS* #### Case Report A 48-year-old African-American female presented with weight loss, abdominal pain, and increasing abdominal girth. She was found to have a pelvic mass and was referred to a gynecologic oncologist for further care. Exploratory surgery revealed a 25 × 24 × 15 centimeter mass arising from the left ovary and adherent to the transverse colon, splenic flexure, descending colon, and small bowel. Tumor debulking as well as a total abdominal hysterectomy, bilateral salpingo-oophectomy, omentectomy, partial small bowel resection and partial colectomy were performed. The tumor contained fat, greasy fluid, and tufts of black hair consistent with a dermoid cyst. Histopathology confirmed a high-grade squamous cell carcinoma arising in the dermoid cyst. No distant metastatic disease was found. Using the FIGO staging system, the patient was deemed to have Stage III disease. Her postoperative course was uncomplicated, and she has now started combination chemotherapy consisting of paclitaxel 175 mg/m2 IV along with carboplatin AUC 6 IV at three-week intervals, with a plan for the patient to receive six cycles. Malignant transformation is a rare pathologic occurrence in mature cystic teratomas (MCT). Squamous cell carcinoma is the most common malignancy seen. Patient age and tumor size are important prognostic factors in distinguishing malignant transformation from benign MCT preoperatively. Malignant transformation is seen in an older patient population, with a median age of 50-55 and in those with a larger tumor burden, with a median size of 10-15 centimeters. Multiple tumor markers may also be useful, including the squamous cell carcinoma antigen and CA-125 levels, but results have been variable. The initial treatment of squamous cell carcinoma arising in MCT is surgical debulking. Due to the rarity of this tumor, there is no general consensus for postoperative treatment. For Stage IA disease, surgical resection followed by close follow-up appears to be adequate therapy. Multiple regimens have been used for more extensive disease, with varying results. As cisplatin has been effective in both ovarian carcinoma and squamous cell carcinoma of the cervix, it has become a mainstay of treatment in regimens for squamous cell carinoma in MCT. ### 124 A CASE REPORT OF HEPARIN INDUCED THROMBOCYTOPENIA AND COLON CANCER T.T. Buck1,2, M. Choi1,2 * 1University of Mississippi Medical Center, Jackson, MS and 2VA Medical Center, Jackson, MS* #### Case Report Introduction Heparin induced thrombocytopenia (HIT) is a drug- induced type of thrombocytopenia. It has been reported with an overall incidence of approximately 2.6% in heparin exposed patients (Martel et el, Blood 2005). Most importantly, patients are at increased risk for developing arterial and venous thrombosis, which causes significant morbidity and mortality. Some studies report up to 20-30% mortality with heparin induced thrombocytopenia. Although colorectal cancer is a common malignancy, only approximately 150,000 cases are diagnosed annually. Approximately 50,000 people die annually from colorectal cancer (Jemal et el CA Cancer J Clin. 2008). Here we present a patient with HIT and colon cancer. Case A 65 y/o white male who originally presented with abdominal pain and constipation, was found to have a near obstructing right colon adenocarcinoma. The patient subsequently underwent right hemicolectomy without complications. He received heparin for DVT prophylaxis during hospitalization. Several days after discharge, he presented to an outside hospital with mental status changes, nausea, and vomiting. He was diagnosed with necrotic small bowel, and underwent resection. Postoperatively he developed multiorgan system failure and sepsis. He was also found to have bilateral pulmonary emboli and was started on heparin. He was eventually stabilized and was transferred back to the VA after being on heparin for about 2 days. 3 days after transfer, it was noted that his platelets decreased from 140K to 56K. HIT was suspected, and he was started on a direct thrombin inhibitor. His HIT AB returned positive, his platelets began to increase and he was discharged on warfarin therapy. He is now awaiting adjuvant chemotherapy for his colon cancer. Discussion It is known that patients with cancer are at increased risk for thrombosis, and heparin products are used to treat thrombosis. However, HIT in cancer patients is relatively rare. Here we present a colon cancer patient, who underwent resection, then subsequently developed HIT. He was treated with a direct thrombin inhibitor, with resolution of thrombocytopenia. He was discharged on warfarin and is now awaiting treatment for colon cancer. ### 125 HEPATIC ADENOMA OF THE LIVER DEVELOPING AFTER CHEMOTHERAPY IN A CHILD WITH HIGH GRADE GLIOMA S. Chandra1, E. Manci2, M. Durham3, A. Rao1 * 1University of South Alabama, Mobile, AL; 2University of South Alabama, Mobile, AL and 3 Emory University School of Medicine, Atlanta, GA*. #### Case Report Introduction: Hepatic adenoma of the liver is an uncommon, benign tumor in children and must be differentiated from malignant hepatic lesions. We present an unusual case of hepatic adenoma of the liver in a child with high grade glioma. We believe this is the first reported case of hepatic adenoma developing after chemotherapy for high grade glioma in a child. Case: An eleven year old white female presented to our institution with a three day history of headache and vomiting. MRI of the brain done secondary to papilledema revealed a 3 cm right parietal mass with a satellite lesion in the globus pallidus. The primary tumor was resected. Histopathology was consistent with a high grade glioma. Post-operatively, she was treated with radiotherapy to the primary and satellite tumor bed. Maintenance chemotherapy was given which included temozolamide and lomustine. Four weeks later, she developed nausea, vomiting, dehydration and loss of weight. On evaluation, she had clinical evidence of gastric outlet obstruction and pancreatitis. CT showed a hypodense mass within the left lobe of the liver measuring 12.0 cm X 7.5 cm compressing the gastric outlet. MRI of the brain was negative for tumor recurrence. The mass was completely resected with resolution of her symptoms. Pathology of the mass was suggestive of hepatic adenoma. In retrospect, patient had never been on hormonal contraception. Adenoma was attributed to chemotherapy and all further chemotherapy was discontinued. The child is currently a year out from diagnosis and in remission, doing well off therapy. Conclusion: We believe this is the first reported case of hepatic adenoma developing after chemotherapy in a pediatric patient with high grade glioma. Hepatic adenoma is an uncommon benign tumor of the liver, particularly in childhood. The detection of hepatic nodules, especially in children with cancer, raises the possibility of metastases. The prevalence of benign liver nodules in patients on chemotherapy should be in the differential when such hepatic masses are noted especially if corroborated by radiologic findings and may help alleviate parental anxiety. ### 126 CYCLOSPORINE INDUCED DIABETES MELLITUS IN A PATIENT WITH APLASTIC ANEMIA- A CASE REPORT V.R. Damerla1, P. Surampudi2, H. Safah1 * 1Tulane University Medical Center, New Orleans, LA and 2Tulane University Medical Center, New Orleans, LA*. #### Purpose of Study This is a documented case of diabetes mellitus in a patient on cyclosporine for aplastic anemia. #### Methods Used A 71-year old African American male with history of newly diagnosed aplastic anemia with no prior history of type 2 diabetes mellitus or history of steroid use was admitted for non transplant treatment of Aplastic Anemia. Immuno-suppressive therapy consisting of rabbit-antithymocyte globulin 3.5 mg/kg IV for 5 day, intravenous methylprednisone 1 mg/kg/day and oral cyclosporine 6mg/kg/day in two divided doses was started. Prior to initiation of treatment, his plasma glucose levels were within normal range over 5 years. The patient achieved therapeutic cyclosporine level on day 2(cyclosporine 200-400 mMol/L). The cyclosporine levels were noted to be supra-therapeutic on day 5 (500 mMol/L) while on cyclosporine 420 mg twice daily. Despite reduction in cyclosporine dose to 350 mg twice daily and discontinuation of steroids on day 7 of treatment, patient was noted to have continued elevated plasma glucose levels at 257 mg/dl. On day 10 of cyclosporine mono-therapy, the cyclosporine levels were still supra-therapeutic (450 mMol/L) with plasma glucose of 190 mg/dL. Patient was re-admitted for decreased oral intake and dehydration on day 17 and noted to have plasma glucose of 550 mg/dl and cyclosporine levels >500 mMol/L. The elevated plasma glucose still present 10 days post discontinuation of steroids was highly suggestive of cyclosporine induced glucotoxicity. Following normalization of cyclosporine levels, better glucose control was attained in the hospital setting. After lowering cyclosporine levels to 200- 250 range, better glucose control was attained. Patient continues to be Insulin dependent. #### Summary of Results No #### Conclusions Case reports of calcineurin inhibitors induced hyperglycemia have been published in the transplant setting. This adverse event is seen more with Tacrolimus compared with cyclosporin. The mechanism of injury is not well defined. This is the first case report of of such an adverse event developing in a patient with aplastic anemia.Physicians using calcineurin inhibitors such as cyclosporine must closely monitor patients for hyperglycemia particularly in cases with supra-therapeutic doses of immunosuppression. ### 127 HODGKIN'S LYMPHOMA PRESENTING AS HEMATURIA V. Dembla, S. Elkins, J. Files *UMMC, Jackson, MS*. #### Case Report 42 year old male with no significant past medical history, presented with hematuria. He is a non-smoker and drinks alcohol socially. Review of systems was positive for hematuria and negative for renal stones, weight loss, night sweats, fever, abdominal pain,low back pain, melena, or hemoptysis. On physical exam, he was obese with a weight of 336 pounds, and blood pressure of 130/72 mm Hg. The rest of examination was unremarkable with no palpable lymphadenopathy in the supraclavicular, cervical, axillary or inguinal areas. Laboratory analysis showed a white cell count 5800 cells/ cmm, hematocrit 45.7 percent and platelet count 260,000/ cmm. Renal function showed creatinine of 1.6 mg/dl and calcium of 11.0 mg/dl, and normal liver function tests. He underwent cystoscopy and a nodular urinary bladder mass was found. Computerized tomography scans revealed borderline sized retroperitoneal and bilateral inguinal lymph nodes measuring 11 mm, which were also positive on positive emission tomography (PET) scan. Additionally PET scan revealed increased uptake in the spleen and suspected mesenteric lymphadenopathy. Urinary bladder biopsy revealed lymphocyte predominant Hodgkin's Lymphoma as did biopsy of pelvic lymph node. Slides were sent to the Mayo clinic for review and they concurred with the original diagnosis. Immunohistochemistry was positive for CD 45 and CD 20 and negative for CD 15 and CD 30. Bone marrow biopsy showed 60 percent cellularity without lymphomatous involvement. Gated heart scan and pulmonary function tests were normal. For Stage IV AS Hodgkin lymphoma, he was treated with Doxorubicin, Bleomycin, Vinblastine and Dacarbazine. Given a large lymph node field, radiation therapy was avoided. He was given a total of five chemotherapy cycles with resolution of bulky lymphadenopathy and clearing of bladder mass per repeat cystoscopy and subsequent complete response. He had recurrence of hematuria and repeat cystoscopy showed suspicious lesion in the urinary bladder. Biopsies of bladder and prostate were performed and confirmed recurrent lymphocyte predominant Hodgkin's lymphoma with features suggestive of large B cell transformation. It was positive for CD 20 and negative for CD 15 and CD 30. Repeat imaging showed lymphadenopathy in the pelvic and bilateral iliac lymph nodes. He is soon to start with salvage chemotherapy. ### 128 RETROSPECTIVE REVIEW OF ADJUVANT TREATMENT OF ADVANCED RENAL CELL CARCINOMA WITH ORAL TYROSINE KINASE INHIBITORS J. Frost, R.D. Hamilton *University of Mississippi Medical Center, Jackson, MS* #### Purpose of Study To identify patients treated at an academic medical center with advanced renal cell carcinoma, review patient characteristics, and evaluate response to adjuvant chemotherapy with tyrosine kinase inhibitors. #### Methods Used Patients diagnosed with stage IV renal cell carcinoma or relapsed renal cell carcinoma over a two-year period were identified. Information on each patient including age, race, gender, prior nephrectomy, sites of metastatic disease, treatment received with responses were collected. #### Summary of Results Thirteen patients were identified with sufficient evaluable data. 7 patients were African American and 6 patients were Caucasian. 6 patients were females and 7 patients were males. The average age was 48 years, the range was 33 to 62 years old. The most common site of metastatic disease was pulmonary metastases as seen in 11 of the 13 patients reviewed. The other less common sites were liver (1 patient) and bone (1 patient). Ten of the 13 patients recieved radical nephrectomies. Eight patients recieved either Sunitinib or Sorafenib as single agents or as sequential therapy. Two patients were treated with Sunitinib and 1 patient received a partial response (PR) lasting for 9 months and the second patient with palliation of symptoms for 3 months. Three patients were treated with Sorafenib, 1 patient had a PR for 3 months and the other 2 patients were administered Sorafenib for 3 weeks prior to death. Three patients were treated with sequential Sorafenib and Sunitinib. Of these patients, 2 patients recieved a PR of 5 months with each agent and the third patient was intolerant of Sunitinib but had a PR with Sorafenib lasting 3 months. Four of the 13 patients reviewed did not recieve treatment, one patient died within a month of diagnosis, one with nephrectomy and metastectomy that had a complete response after Interferon, one patient that was lost to follow up and one patient with stable pulmonary metastates on observation. #### Conclusions Oral tyrosine kinase inhibitors are the newest agents in the treatment of advanced renal cell carcinoma. The results are promising with a trend towards partial response of 3 to 5 months at our acedemic center. However the data is early and continued research into the use of oral tyrosine kinase inhibitors in advanced renal cell carcinoma is needed. ### 129 ORBITAL METASTASIS FROM PROSTATE CANCER N. Koshy1, A. Mathew2 * 1Feist Weiller Cancer Center, Shreveport, LA and 2LSUHSC, Shreveport, LA*. #### Case Report A 62 year old man with history of metastatic prostate cancer presented with left eyelid swelling associated with proptosis. MRI face and orbit was done which showed band like curvilinear enhancing mass mainly occupying the lateral and superior portions in the left orbit (arrow-Panel A). He underwent orbitotomy with removal of the mass and immunohistochemical staining was positive (red-brown staining of the cytoplasm) for prostate specific acid phosphatase (arrows-Panel B). He was subsequently referred for local radiation therapy. On follow up after radiation therapy his proptosis had significantly improved. The proportion of metastatic orbital cancer arising from prostatic carcinoma is only 4%. These patients most commonly present with decreased vision, periorbital pain and proptosis. This case is presented to remind both radiologists and clinicians of the diagnosis of metastatic prostate carcinoma to the orbit and the usefulness of histochemical staining of biopsy material for prostate specific acid phosphatase. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F7.medium.gif) [Figure.](/content/57/1/301/F7) Figure.   ### 130 SPLENIC SEQUESTRATION IN AN ADULT WITH HbSS N. Koshy1, A. Mathew2 * 1Feist Weiller Cancer Center, Shreveport, LA and 2LSUHSC, Shreveport, LA* #### Case Report Acute splenic sequestration crisis(ASSC) and splenomegaly, while common in young children with sickle cell anemia, is rare in adults homozygous for Hemoglobin S (HbSS) due to their scarred and fibrotic spleens resulting from repeated episodes of splenic sequestration and infarction during the course of their childhood. Case report A 36 year old African American woman, first diagnosed with sickle cell anemia at 33 years of age following a pain crisis, was admitted for evaluation of fatigue, shortness of breath, pain in the back and left flank. She had multiple admissions in the recent past for pain crises and anemia for which she received many units of packed red blood cells. During one of the hospitalisations Hb electrophoresis showed HbA- 0.0, HbS- 79.5, HbC- 0.0, HbA2- 4.2, HbF -16.3. On this admission the Hb electrophoresis showed HbA- 29.6, HbS- 54.5, HbF- 12, HbA2-3.8. The change in electrophoresis pattern was due to blood transfusions received in the past. Her Hb upon admission was 6.9 g/dl, reticulocyte count- 10.7% and the platelet count-87,000. The Hb failed to rise despite transfusing 2 units of PRBC. The spleen was easily palpable 8-10 cm below the left costal margin. The LDH level was 502U/L and haptoglobin level less than 8. The total bilirubin was 5.0 mg/dl. In the light of the jaundice and worsening anemia attributed to the splenic sequestration and the laboratory values which indicated an active hemolytic process, an emergency splenectomy was performed to prevent a fatal sequestration crisis. Pathology revealed congestive splenomegaly in a spleen weighing 1200 g. Acute splenic sequestration crisis, a potentially life threatening anemic crisis occurring in sickle cell anemia, is characterized by sudden enlargement of the spleen due to entrapment of a significant portion of circulating red cell mass, sudden decline in the hematocrit with or without thrombocytopenia and circulatory collapse due to loss of circulating blood volume. The case is reported to underscore the fact that while treating an adult with HbSS in sickle cell crisis, a clinical index of suspicion is to be maintained and regular monitoring of spleen size should be done to avoid missing acute splenic sequestration crisis, a rare but catastrophic entity ### 131 PERIPHERAL T-CELL LYMPHOMA (PTCL) IN A PEDIATRIC PATIENT WITH MYELODYSPLASTIC SYNDROME (MDS) C.A. Morrison1, M. Luquette2, L. Yu1 * 1Louisiana State University, Children's Hospital, New Orleans, LA and 2Louisiana State University, Children's Hospital, New Orleans, LA*. #### Purpose of Study MDS, a preleukemic condition, accounts for 3-7% of childhood cancers. A 9 y/o presented with myalgias, fever and cervical adenopathy. On exam, he was ill appearing and pale. There was evidence of diffuse lymphadenopathy. He was diagnosed with MDS. Adenopathy is an unusual presenting sign of MDS. Upon further evaluation, PTCL was discovered. PTCL is mostly seen in adults, representing less than 15% of all lymphomas. It is even more rare in children. The clinical course is aggressive and relapses are common. We present a pediatric case involving MDS and PTCL. #### Methods Used Diagnostic evaluation consisted of a BM biopsy/aspirate, Lumbar puncture, full body CT, gallium and bone scans, lymph node and skin biopsies. #### Summary of Results Full body CT scan showed diffuse lymphadenopathy. BM biopsy/aspirate revealed MDS- RAEB. Cytogenetics showed t (3:7)(q25; p15), del (11)(q14q23) and del18 (q2), abnormalities associated with MDS. Node biopsy revealed PTCL. Analysis of the node by flow cytometry revealed CD7 + and CD3- cells. Immunohistochemistry demonstrated CD3 +, CD5 +, TdT- and CD34- cells. CD3 +, CD20- cells were isolated from the skin biopsy, indicating perivascular malignant T-cell infiltrate. Therapy consisted of Induction - Vincristine (1.5 mg/m2), Daunorubicin (30 mg/m2), L-asparaginase (6,000 IU/m2), Prednisone (60 mg/m2) and Intrathecal Methorexate (ITM) (12 mg) and Cytarabine (70 mg); Consolidation- Cyclophosphamide (1000 mg/m2), Cytarabine (75 mg/m2), 6-mercaptopurine (60 mg/m2), and Prednisone, ITM; Interim Maintenance- 6-mercaptopurine (25 mg/m2), High dose Methotrexate (5 grams/m2 with leucovorin rescue) and ITM. Diffuse lymphadenopathy resolved soon after start of therapy. While in VGPR, he underwent myeloablative SCT from his HLA-ID sibling. There was evidence of engraftment on Day + 8. He had no major complications and was discharged within three weeks. #### Conclusions The association between MDS and leukemia, especially AML has been well documented. There has not been a prior report of association between MDS and peripheral T-cell lymphoma. The response to conventional chemotherapy is poor therefore innovative treatments such as SCT need to be considered. ### 132 AN UNUSUAL CASE OF PELVIC PLASMACYTOMA IN A PATIENT POST AUTOLOGOUS TRANSPLANT FOR MULTIPLE MYELOMA AND PLASMACYTOMA OF JAW AND SPINE S. Radhi, N. D'Cunha, E. Cobos *Texas Tech University/Lubbock, Lubbock, TX*. #### Case Report Plasmacytoma is a solitary mass of neoplastic monoclonal plasma cells in either bone or soft tissue. Plasmacytoma of the pelvis is rare. Herein, we report a case of large pelvic plasmacytoma arising in a patient with a history of multiple myeloma and plasmacytoma of jaw and spine who under went autologous stem cell transplantation. A 54 year-old male presented with mass and fracture of right mandible. Biopsy of mass revealed 50% monoclonal plasma cell with lambda light chain consistent with plasmacytoma. Further investigation revealed soft tissue mass at 8th thoracic vertebra encroaching the spinal cord. Skeletal survey revealed diffuse lytic lesions with pathological ribs fracture Bone marrow examination revealed 37% atypical plasma cell. Cytogenetic was normal. Serum revealed 5.21g/dl IgA lambda M-spike, beta2 microglobulin 3.5 and albumin 3gm%. Urine revealed lambda light chain. Patient was treated with titanium rod to jaw bone, radiation to jaw and spine followed by systemic therapy with dexamethasone and thalidomide for 6 months. The patient went into remission for two month followed by recurrence. He was salvaged with bortezomib followed by autologous stem cell transplant. Patient was in remission for 16 month post transplant. He then presented with fever and bleeding per rectum. Colonoscopy revealed a large fungating, circumferential mass partially obstructing the sigmoid colon. Biopsy showed plasmacytoma.Because of bleeding and obstruction and to prevent complication during radiation, the patient underwent exploratory laparotomy, which revealed 20 cms × 30 cms mass in the low pelvis invading the sigmoid colon and bladder. The mass was resected followed by sigmoid colectomy and colocolostomy reconstruction. Due to bladder invasion partial cystectomy with stent placement was done. Post surgery the patient was treated with radiotherapy to the pelvis and chemotherapy. Conclusion: Patients with multiple myeloma and GI bleed, it is essential to consider intestinal or pelvic plasmacytoma in the differential diagnosis. Extensive bowel and bladder involvement should be treated with surgery prior to radiation to prevent complication. ### 133 AN UNUSUAL PRESENTATION OF SMALL CELL CARCINOMA OF THE LUNG E. Rickman, K. Holt, J. Stewart *University of Mississippi Medical Center, Jackson, MS*. #### Case Report Small cell lung cancer is an aggressive subtype of lung cancer known to metastasize early to distant sites. The patient is a 58 year old African American male with a 60 pack-year smoking history who presented to the emergency room with a 2 week history of nausea, vomiting, and diarrhea. He reported 1-2 episodes of nausea and vomiting and 7-8 episodes of diarrhea daily. He also described a 30-pound weight loss during the 1-2 months prior to admission. On presentation he was afebrile and tachycardic, and physical examination was significant for a distended, non-tender abdomen with bowel sounds in all quadrants. He was also noted to have a 4-5 cm firm, non-tender nodule on his right posterior shoulder. Lab work revealed a lipase >1600, creatinine of 2.3, and white blood cell count of 24. An initial chest X-ray showed a 2 cm non-calcified mass in the left upper lobe of his lung. By hospital day number 2, the patient's symptoms had improved with bowel rest and intravenous fluids. After restarting his diet, the patient began having abdominal pain, and his symptoms worsened again. A CT of the chest, abdomen, and pelvis showed a right posterior 4.5 × 3.5 cm back mass and a 4 × 2 cm left upper lobe lung mass extending from the left hilum. It also showed a 4 × 2 cm pancreatic mass with resultant gastric outlet obstruction. Other CT findings included significant abdominal adenopathy and irregularities of the proximal cecal wall. The patient subsequently underwent a fine needle aspiration of the right shoulder mass, and the pathology showed metastatic small cell carcinoma. Pathology from biopsy of the pancreatic mass was also consistent with metastatic small cell lung cancer. A CT of the head was negative for metastasis. On hospital day number 10, the patient underwent open gastrojejunostomy and celiotomy. His course was then complicated by a right lower extremity deep venous thrombosis as well as abdominal wound dehiscence. He was initially placed on total parenteral nutrition postoperatively, but tolerated a clear liquid diet after several days. The patient elected not to undergo chemotherapy and was discharged home with home hospice. This case reiterates the aggressive nature of small cell lung cancer; it also highlights the association of skin metastasis of small cell lung cancer with poor prognosis. ### 134 HEPATIC SEQUESTRATION AND ELEVATED CA 19-9 IN A PATIENT WITH SICKLE CELL ANEMIA S.T. Sarva, C. Paba, R.U. Osarogiagbon *University of Tennessee Health Science Center, Memphis, TN*. #### Purpose of Study Hepatic sequestration crisis is a rare but serious complication of sickle cell anemia, characterized by pooling of sickle red blood cells in the hepatic sinusoids, leading to rapid, tender hepatomegaly, a plummeting hematocrit and hypotension. This case describes a sickle cell patient with hepatic sequestration crisis who had coexisting peri-pancreatic lymphadenopathy. #### Methods Used A 38-year-old African American male with a history of sickle cell anemia presented with a 2-day history of generalized body pain and shortness of breath. His past history included acute chest syndrome, iron overload, and pulmonary hypertension. On physical examination, he was alert, oriented, pale and icteric. His abdomen was distended, a mildly tender liver was palpable 6 cm below the right costal margin. Abdominal CT scan showed an enlarged liver, a mass near the head of the pancreas and several retroperitoneal masses. A technetium colloid SPECT did not show any evidence of extra-medullary hematopoeisis in the abnormal masses. CA19-9 was elevated to 299.5, raising a suspicion of co-existing pancreatic cancer. Initially the patient was managed conservatively with intravenous hydration and narcotics. His clinical condition deteriorated over the course of 2 days: his hemoglobin dropped by 3 g/dL, liver span increased to 10 cm and became extremely tender. His total bilirubin, BUN and creatinine increased by 5 fold. #### Summary of Results A clinical diagnosis of hepatic sequestration crisis was made and the patient was managed aggressively with exchange transfusions. This approach led to a rapid recovery. His hemoglobin stabilized, bilirubin trended back to initial levels and his liver size decreased to 4 cm. Hepatic enzymes and renal panel returned to normal. The CA19-9 dropped to 242 at the time of discharge. #### Conclusions Hepatic sequestration crisis is an infrequently identified complication of sickle cell anemia in adults. The pathophysiology is identical to childhood splenic sequestration. Early recognition and aggressive management are essential to avoid the mortality risk which results from acute multi-organ failure. CA19-9 is not reliable in the presence of biliary obstruction, and should be interpreted with caution in patients with high levels of serum bilirubin. ### 135 OVARIAN CANCER IN A MAN? A.L. Sumrall1, L. Puneky1, S. Bigler2, S. Elkins1, T. Thigpen1, * 1University MS Medical Center, Jackson, MS and 2University MS Medical Center, Jackson, MS*. #### Case Report A 72 year old male with past medical history of COPD, paroxysmal atrial fibrillation, and gastroesophageal reflux presented to an outside hospital complaining of left testicular swelling of two months' duration. Physical examination revealed left testicular fullness and a normal right testicle. Initial ultrasound showed a 6 cm × 3.8 cm predominantly cystic mass involving the left testicle. CT scans showed no evidence of metastatic disease. On April 22, 2008, the patient underwent left radical orchiectomy. Preoperative laboratory testing revealed: beta-hcg of <5 MIU/ml, lactate dehydrogenase of 148 U/L, alpha fetoprotein of <2 ng/ml, and CA-125 of 6.1 U/ml. Microscopic examination of tissue from left orchiectomy showed an intratesticular serous papillary cystic tumor with borderline malignancy felt to be identical histologically to the commonly encountered borderline papillary serous tumor of the ovary. The following features were described: A. No invasive growth identified. B. The tumor was unifocal and appeared to be intrinsic to the testis, encompassed by the tunica albuginea. C. There was no involvement of the epididymis or the spermatic cord. D. No vascular or lymphatic invasion was identified. E. The surgical margins were free of neoplasm. ## **Infectious Disease, HIV, and AIDS Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 136 CHRONIC CANDIDA AND CRYPTOCOCCAL MENINGITIS IN HIV POSITIVE PATIENT D.F. Hansen1,2, H. Alshayeb2, Z. Sharif2, M. Kamp2, F. Abu Alrub2, B. Abbasi2, S. Zaidi2, S.N. Haider2 * 1University of Tennessee: Memphis, Memphis, TN and 2University of Tenessee, Memphis, TN*. #### Case Report Case Report: Fungal meningitis represents an AIDS-defining event and occurs typically with very low CD4 + counts. Cryptococcus accounts for most of these cases. Candida meningitis is still a rare clinical condition, although it is becoming frequently reported in immune suppressed states such as patients with drug addicts, cancer patients, organ transplant recipients and HIV/AIDS patients. However, simultaneous candidal and cryprococcal meningitis in HIV positive patients has been rarely reported. Therapeutic options are limited with an often guarded prognosis. Classically, amphotericin and flocytosine are initial treatment, followed by fluconazole. This report represent a 42 year old patient with a PMHx of HIV, AIDS with CD4 count of 28 non-compliant with HAART therapy, who presented with fever, headache, nausea, and neck stiffness for 2 weeks. The patient denies history of IV drug abuse. Temperature: 37 C, Bp: 110/70, HR: 110. No oral thrush seen. Neck stiffness with positive Kering's sign illicited. Fundoscopic exam normal. Laboratory work up revealed a WBC: 2.4, HTC: 30, Plt: 240. Cr: 0.7, liver transaminases normal. CT scan of the head was normal. On LP, opening CNS pressure was 34 cm H2O, CSF was clear with 340 cells with lymphocytic predominance, proteins: 6 g/l, glucose: 60 mg/dl, cryptococcal antigen positive with a 1/280 titer. Treatment was initiated with liposomal amphotericin B. CSF bacteriologic cultures were negative, however CSF mycological cultures grew Candida albicans. AFB smears and cultures were also negative. Daily therapeutic LPs were performed to decrease opening pressure. Cultures cleared for Candida albican on the 4th set sent on Day 13 with associated resolution of leukocyte pleocytosis and normalization of CSF protein and glucose. Patient completed the first 6 weeks of liposomal amphotericin with no relapse in his headache. Patient will complete his treatment course with fluconazole as an outpatient. Conclusion: To our knowledge, this is one of the rare reported cases of simultaneous candidal and cryptococcal meningitis in an HIV positive patient. Follow up of this patient while he completes his course of treatment is in progress. ### 137 INCOMPLETE KAWASAKI DISEASE WITH REACTIVATION OF A BCG INOCULATION SITE M. Hollister1, J. Bocchini1, Y. Abe2 * 1Louisiana State University Health Sciences Center, Shreveport, LA and 2Louisiana State University Health Sciences Center, Shreveport, LA*. #### Purpose of Study Kawasaki disease (KD) is an acute, self-limited vasculitis with possible serious sequelae if untreated. This case emphasizes the importance of recognizing the various clinical presentations of KD. #### Methods Used Clinical vignette. #### Summary of Results A 10-month-old Japanese female presented with a five day history of high fever, bilateral bulbar conjunctival injection, diffuse maculopapular rash, and reactivation of her Bacillus Calmette-Guerin (BCG) inoculation site. She was afebrile the day prior to her emergency room visit. On physical examination, she had multiple vesicles on her upper left arm. She received an intradermal BCG vaccination at this site at five months of age. Laboratory investigations revealed a normal leukocyte count (10,250 [normal 6,000-17,500]/μL) with a normal differential (31% neutrophils and 57% lymphocytes), normal hemoglobin (11.9 [normal 10.5-13.5] g/dL), and normal platelets (370,000 [normal 142,000-405,000]/μL). The erythrocyte sedimentation rate (69 [normal 0-20] mm/h) and the C-reactive protein (5.34 [normal 0-0.5] mg/dL) were elevated. The urinalysis had 15 mg/dL of protein and 10-20 white blood cells/HPF. The urine and blood cultures were negative. An echocardiogram showed normal coronary vessels with a small pericardial effusion. Incomplete KD was diagnosed and she was placed on six weeks of aspirin therapy (5 mg/kg/day). The patient's father declined IVIG therapy because there was no evidence of coronary vessel disease and the patient had become afebrile. About two weeks later, she developed desquamation of the third and fourth fingertips of the right hand and part of the right palm. The reactivated BCG site had dried and was also peeling at this time. Her systemic inflammatory response improved with an erythrocyte sedimentation rate of 38 mm/h and a C-reactive protein of 2.52 mg/dL. A repeat echocardiogram was normal. The reactivation of her BCG inoculation site was completely resolved within six months. #### Conclusions Due to the possible serious sequelae of untreated KD, it is important to recognize the various clinical presentations of this disease. The development of skin lesions at the BCG inoculation site is now recognized as an important diagnostic sign of KD. ### 138 EMERGENCE OF LINEZOLID-RESISTANT STAPHYLOCCUS AUREUS IN CYSTIC FIBROSIS A. Inman1, N. Harik3, T. Beavers-May2, H. Maples4 * 1UAMS College of Pharmacy, Little Rock, AR; 2Arkansas Children's Hospital, Little Rock, AR; 3UAMS College of Medicine, Little Rock, AR and 4UAMS College of Pharmacy, Little Rock, AR*. #### Purpose of Study The incidence of resistant strains of Staphylococcus aureus is increasing. We report a case of methicillin resistant Staphylococcus aureus (MRSA) resistant to linezolid, isolated multiple times from a patient with cystic fibrosis. Our goal was to determine if these isolates were similar to reported linezolid-resistant strains and if therapy with linezolid affected the development of resistance. #### Methods Used A chart review was conducted to ascertain initiation of linezolid, impact of resistance on pulmonary function tests and hospitalizations. Confirmation of linezolid resistance was conducted through a variety of methods. The isolates were sub-cultured onto blood agar plates to ensure viability and purity. They were retested on the BD Phoenix, E-test, and VITEK 2 to confirm linezolid resistance. Isolates will be subjected to genetic testing using the multilocus sequence typing method (MLST). This will determine if isolates are genetically identical or if there are a variety of strains represented. This will also allow for comparison to strains acquired from the Network on Antimicrobial Resistant Staphylococcus aureus (NARSA). #### Summary of Results Linezolid 600 mg given twice daily by mouth was originally initiated and used periodically in the patient prior to development of linezolid resistance 2 years later. No significant clinical difference based on pulmonary function testing was seen once linezolid resistance developed. Several isolates were found to have genetic similarity to strains of linezolid-resistant MRSA acquired by NARSA. #### Conclusions Linezolid resistant MRSA was observed in a patient with cystic fibrosis after being treated with standard linezolid dosing. The increasing lack of viable options for outpatient antimicrobial therapy makes the discovery of linezolid resistance particularly troublesome. Knowing that pediatric CF patients have increased clearance and volume of distributions lead most medications to be dosed at an increased mg/kg/dose or increased frequency. Further pharmacokinetic studies need to be performed in special populations to ensure appropriate dosing of linezolid to help prevent further development of resistance. ### 139 PRIMARY AMEBIC MENINGOENCEPHALITIS- A CASE REPORT IN THE SOUTH J.L. Kennedy3, S.M. Schexnayder2, M. Moss2, M. Tailounie2, L. Ortmann2, J. Byrnes2, S.H. Stovall1 * 1Arkansas Children's Hospital, Little Rock, AR; 2Arkansas Children's Hospital, Little Rock, AR and 3Arkansas Children's Hospital/University of Arkansas for Medical Sciences, Little Rock, AR*. #### Purpose of Study Primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri, a thermophilic, fresh water amoeba, occurs in previously healthy children and young adults with a recent history of water-sports activities. #### Methods Used We present a case report of a healthy 14 year old caucasian female with vomiting, fever, and headache and was diagnosed with PAM. #### Summary of Results The patient presented to her local hospital with headache, nausea, and stiff neck for two days. The patient had been to a lake in Oklahoma two weeks earlier. She was admitted to a local hospital and with a diagnosis of viral meningitis after lumbar puncture showed 533 WBC (41% PMNs, 51% lymphs) with glucose 67 mg/dl, protein 98 mg/dl and a negative gram stain. The night of admission, she developed tonic clonic seizure activity. She was intubated for a decreased level of consciousness and was transferred to our tertiary care facility. On arrival at our facility a repeat lumbar puncture showed many WBC including 36 "other cells" with high protein and low glucose levels in CSF. Continuous EEG monitoring was begun and empiric antibiotics started. A head CT scan showed diffuse cerebral edema. Lab personnel reported "other cells" in CSF were suggestive of amoeba. Liposomal amphotericin B, rifampin, and fluconazole were begun after infectious disease consultation. CSF photos sent to the CDC confirmed the diagnosis of Naegleria fowleri. She developed anisocoria consistent with increased intracranial pressure and received osmotic therapy. An MRI the following day showed pus within the quadrigeminal plate cistern and leptomeninges. She subsequently developed bradycardia and hypotension, followed by a brief cardiopulmonary arrest. An external ventricular drain was placed, intracranial hypertension confirmed and intraventricular amphotericin B administered. The following day, her clinical examination confirmed brain death. An autopsy was performed. #### Conclusions This is a single case report of a pediatric patient with primary amebic encephalitis with N. fowleri resulting in rapid death despite aggressive therapy. ### 140 CHLAMYDIA PNEUMONIAE INFECTIVE ENDOCARDITIS A. Lacasse, R. Odero, M.S. Gelfand *UT Health Science Center Memphis, Memphis, TN*. #### Case Report Infective endocarditis (IE) is culture negative in 2 to 7% of cases, with a higher incidence in developing countries. Antimicrobial use prior to culture remains the most common cause but recent improvements in microbiological and molecular techniques have led to a higher diagnostic yield. The most commonly isolated organisms in culture-negative IE include: Coxiella burnetii, Bartonella species as well as Abiotrophia species and Candida species. IE due to Chlamydia species, including Chlamydia pneumoniae, is very rare. Most cases are diagnosed by serology but valvular tissue-directed polymerase chain reaction (PCR) can be used. The treatment of choice is doxycycline. We report a case of Chlamydia pneumoniae IE diagnosed by serology without evidence of bacteria by valvular PCR analysis. A 46-year-old man with a background of diabetes mellitus, hypertension and obesity first presented with a 3-month history of fever, chills, diaphoresis and progressive dyspnea on exertion. Echocardiogram was consistent with severe aortic insufficiency and presence of a vegetation. Due to severe dental caries, patient underwent extraction of 21 teeth. Blood cultures remained negative. Acute clinical deterioration led to emergent aortic valve replacement. Intraoperative finding of partial mitral valve (MV) destruction also led to its replacement. Bioprosthetic valves were used. Native valve bacterial and fungal stains were negative but cultures were not obtained. After recovery and successful completion of a 6-week course of ampicillin/sulbactam and streptomycin, fever and dyspnea recurred. Serial transesophageal echocardiograms were consistent with a MV perivalvular leak. Six months after initial bivalvular replacement, patient underwent a redo MV replacement. Intraoperative purulence was observed around the bioprosthetic mitral valve but cultures were not obtained. Review of previous laboratory data was significant for a positive Chlamydia pneumoniae serology (IgG titer >1:512). The paraffin-embedded bioprosthetic MV was sent to a reference laboratory for PCR testing but all tests were negative including generic prokaryote 16S rRNA and fungal 18S rRNA. A specific Chlamydia PCR was not performed. Doxycycline was initiated and clinical recovery was achieved. ### 141 PSEUDOMONAS AERUGINOSA SKULL BASE OSTEOMYELITIS WITHOUT OTITIS EXTERNA A. Lacasse, R. Odero, M.S. Gelfand *UT Health Science Center Memphis, Memphis, TN*. #### Case Report Skull base osteomyelitis is usually encountered as a rare complication of advanced or unrecognized malignant otitis externa, most commonly involving the temporal bone. Pseudomonas aeruginosa (PA) is the causative organism in the majority of cases. We report here a case of PA skull base osteomyelitis with atypical features and absence of otitis externa. A 74-year-old man with a background of coronary heart disease and chronic atrial fibrillation presented with a 3-month history of intense continuous left-sided fronto-temporal headaches, recently associated with progressive hoarseness, dysphagia, dysarthria and weight loss. He was afebrile with normal hemodynamics. Physical examination was remarkable for left-sided hearing loss and cranial nerve IX, X and XII palsies. Bilateral ear canal and tympanic membrane examination by an otolaryngology consultant was normal. Laboratory evaluation did not show any abnormalities except for an erythrocyte sedimentation rate of 86. Computed tomography of the head revealed a skull base mass immediately anterior to the clivus and left maxillary sinus opacification. An endoscopic transnasal biopsy showed nonspecific chronic inflammatory changes without granulomata. Routine culture grew PA. The patient was treated with an 8-week course of piperacillin-tazobactam and ciprofloxacin. Atypical cases of skull base osteomyelitis can present with non-specific headaches, involvement of the sphenoid or occipital bones, absence of otitis externa and late cranial nerve palsies. Imaging studies play a key diagnostic role. Magnetic resonance imaging is the most sensitive technique: abnormal signal intensity in the clivus (low T1, high T2), pre-clival mass and post-contrast enhancement are important diagnostic features. Associated risk factors include: diabetes mellitus, human immunodeficiency virus infection, chronic sphenoid sinus disease and chronic steroid use. Low burden of organisms can lead to falsely negative tissue culture. PA is isolated much less frequently in the absence of otitis externa; other organisms including Staphylococcus aureus, Aspergillus species and Eikenella corrodens have been reported. ### 142 PANCYTOPENIA AND AIDS: DISSEMINATED HISTOPLASMOSIS IN DISGUISE C.L. Moll, R. Johnson *Louisiana State University Health Science Center, New Orleans, LA* #### Case Report *Histoplasma capsulatum* is a dimorphic fungus endemic to the Ohio/Mississippi river valley. Infection occurs via inhalation and manifests as a self-limited febrile pulmonary infection in immunocompetent patients but may disseminate in the immunocompromised. We report the case of a 37-year-old African American male with AIDS who presented to the emergency department complaining of shortness of breath, fever, weight loss, and abdominal pain. Diagnosed with AIDS one month prior to presentation, his CD4 count was 2 with a viral load of 80,758. He had not been started on antiretroviral therapy. Exam was remarkable for thrush and abdominal distension with diffuse tenderness. He had elevations in total bilirubin and LDH, low albumin, and pancytopenia on initial labs. Chest x-ray illustrated a diffuse interstitial pattern. Bactrim and prednisone were started for presumptive *Pneumocystis jirovecii* pneumonia. Azithromycin was given for prophylaxis against *Mycobacterium avium-intracellulare*. He was placed in isolation and sputum sent for AFB. Despite platelet transfusions, his thrombocytopenia did not improve. Thinking this could be Bactrim induced, therapy was changed to atovaquone. He continued to decompensate and was transferred to the ICU for acute abdomen and respiratory distress. CT of the abdomen showed ascities, hepatosplenomegaly, mesenteric and retroperitoneal lymphadenopathy with severe thickening of the gallbladder. A HIDA scan showed normal filling of the gallbladder with no obstruction. Antibiotic coverage was broadened and a paracentisis performed. Bone marrow biopsy was obtained to evaluate the possibility of infiltrative opportunistic infections. Histoplasmosis was seen on peripheral blood smear, bone marrow aspirate, and peritoneal fluid. Amphotericin B was started and prednisone tapered off. Histoplasmosis is the most common endemic mycoses in AIDS patients and is considered an AIDS defining infection. With the introduction of HAART, the incidence has decreased to 2% in non-endemic and 5% in endemic regions. Chest x-ray can resemble PCP or miliary TB but can also be unremarkable. Left untreated the disease is fatal. A high index of suspicion for DH is warranted in evaluating immunocompromised patients presenting with nonspecific complaints. ### 143 STREPTOCOCCUS AGALACTIAE ENDOCARDITIS IN AN INTRAVENOUS DRUG ABUSER T.A. Nguyen, J. Shellito *Louisiana State University School of Medicine, New Orleans, LA*. #### Case Report Introduction: Streptococcus agalactiae (Group B Streptococcus) is an uncommon cause of bacterial endocarditis, accounting for 1.7% of all cases. Recent reports suggest an increasing number of invasive infections caused by group B streptococcus (GBS) in non-pregnant adults, elderly patients, and chronically immunosuppressed individuals. Risk factors include alcoholism, diabetes mellitus, cancer, malnutrition, injection drug abuse, postpartum and post abortion states, valvular disease, prior endocarditis and HIV infection. Case: A 60-year-old man with a history of hypertension, diabetes mellitus, diabetic nephropathy, hyperlipidemia, peripheral vascular disease, coronary artery disease, cerebral vascular accident and, intravenous drug abuse presented to the emergency department complaining of generalized myalgias, fever, and headache for 2 weeks. Of note, he also had an episode of bacterial endocarditis two years prior requiring surgical mitral valve annuloplasty and IV vancomycin and gentamicin. At admit, his vital signs were pertinent for a temperature of 102.2F and pulse rate of 117/minute. His blood pressure and respiratory rate were normal. Respiratory, abdominal and neurologic examinations were unremarkable. Cardiovascular exam revealed no audible murmurs. Multiple needle tracks were noted on his forearms bilaterally. An initial white blood cell count was elevated with significant bandemia and left shift. He was started on empiric coverage for bacterial endocarditis with vancomycin, rifampin, and gentamicin. Transesophageal echocardiogram revealed a large vegetation on the anterior mitral valve leaflet and an aortic paravalvular abscess. Blood cultures grew S. agalactiae susceptible to penicillin (MIC = 0.125). No foci of infection was identified by physical exam or imaging. Infectious diseases and cardiothoracic surgery were consulted and the treatment regimen was modified to ceftriaxone and gentamicin. Discussion: S. agalactiae endocarditis is uncommon, highly aggressive, and associated with an overall mortality rate of 34%. Medical management alone rarely proves to be successful. This case report underscores the need for increased awareness of S. agalactiae as a cause of infectious endocarditis in injection drug users. ### 144 PULMONARY HISTOPLASMOSIS IN A HEMATOPOIETIC STEM CELL TRANSPLANT PATIENT R. Odero, K. Cleveland, A. Lacasse *University of Tennessee, Memphis, TN*. #### Case Report Histoplasmosis is a fungal infection which is endemic in certain geographic areas. Predisposing conditions include immunosuppressive disorders such as infection with human immuno-deficiency virus, extremes of age, and receipt of immunosuppressive medications. Rarely, it has also been transmitted through solid organ transplantation. Recipients of autologous hematopoietic stem cell transplants, even in areas endemic for the infection, are not usually considered to be at an increased risk for histoplasmosis. A 30-year-old man presented with a one week history of cough and estimated ten pound weight loss. Six months earlier he had undergone autologous hematopoietic stem cell transplantation for stage IVB Hodgkin's Lymphoma which had been refractory to multiple cycles of standard chemotherapy. On physical examination, he was afebrile, hypotensive, tachycardic and had residual firm, rubbery, fixed anterior cervical and bilateral axillary lymphadenopathy. Diffuse crackles were heard bilaterally on auscultation of his chest. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F8.medium.gif) [Figure.](/content/57/1/301/F8) Figure.   Chest radiograph showed multiple military opacities bilaterally. Computed tomography of the thorax and upper abdomen showed bilateral reticulonodular infiltration and hepatosplenomegaly. Cultures of bronchoalveolar lavage (BAL) fluid exhibited exuberant growth of Histoplasma capsulatum. The urinary histoplasma antigen was strongly positive. ELISA for HIV, a Mantoux test for tuberculosis and acid-fast bacillus cultures of BAL fluid were all negative. He responded rapidly to intravenous amphotericin B lipid complex and, in two weeks, was discharged home to complete twelve months of oral itraconazole. ### 145 BILATERAL, SYMMETRICAL HEMATOGENOUS OSTEOMYELITIS IN TWO PATIENTS B.M. Statham2, L. Hodges1, F. Beacham2 * 1LSUHSC, Shreveport, LA and 2LSUHSC, Shreveport, LA*. #### Case Report Background: Hematogenous osteomyelitis involving multiple bone sites is reported to occur in children at a rate of 6.8%-7% in large series. A recent study showed an association with Staphylococcus aureus species that also carry the pvl gene and multifocal disease, but symmetrical involvement was not mentioned. Case Reports: We report 2 patients, both 10 year-old boys, who presented with a recent onset of bilateral ankle swelling, pain, and fever. Neither had a history of trauma, or family history of skin or soft tissue infection, hematological or bone malignancy. Both patients had an elevated CRP and ESR. MRI in both patients revealed bilateral distal tibia/fibula osteomyelitis with subperiosteal abscesses also present. Patient "A" had blood cultures confirming MSSA bacteremia, while patient "B's" culture from his periosteal abscess grew MSSA. Both cultures were sent for further testing of virulence factors which confirmed the presence of the pvl gene. Both patients completed a course of parental nafcillin followed by oral therapy with marked clinical improvement. Discussion: S. aureus accounts for over 50% of all cases of osteomyelitis in children. Solitary long bones are the main targets of infection, most frequently, the femur, tibia and humerus. Although common in neonates, hematogenous osteomyelitis involving multiple sites in previously healthy children is unusual and involvement of symmetrical sites is rare. Previous studies have documented an association with the USA300 strains, as well as, PVL-possessing S. aureus pathogens with complicated musculoskeletal infections. However, there is no association mentioned involving symmetrical sites. The presense of the pvl gene in our patients further supports prior report of the pvl gene relation with increased complications in children with S. aureus musculoskeletal infections. In previously healthy children presenting with multiple site bone disease, osteomyelitis is rarely considered in the differential diagnosis. However, these two cases provide evidence that osteomyelitis should be considered in the differential diagnosis of symmetrical musculoskeletal disease. ### 146 VITAMIN D AS ADJUNCTIVE THERAPY IN REFRACTORY PULMONARY TUBERCULOSIS A.V. Yamshchikov1, A. Oladele2, M. Leonard1, V. Tangpricha3 * 1Emory University School of Medicine, Atlanta, GA; 2Georgia Department of Human Resources, Decatur, GA and 3Emory University, Atlanta, GA*. #### Case Report Vitamin D regulates calcium absorption to promote bone health. Literature also indicates that vitamin D modulates the immune response to tuberculosis (TB) by enhancing antimicrobial peptide secretion in immune cells. Vitamin D has been shown to improve clinical outcomes in patients with pulmonary TB (PTB) in developing countries, but we are not aware of publications describing use of vitamin D to augment clinical response in treatment of refractory PTB in the developed world. Case History: 63 year old African American female with no medical history presented in March 2007 with smear and culture positive PTB, accompanied by cough, pleuritic chest pain, poor appetite, weight loss, and night sweats. Chest radiograph revealed a cavitary infiltrate. Laboratory evaluation was remarkable for HIV negative serostatus, elevated white cell count, and drug susceptible Mycobacterium tuberculosis (M.tb) on sputum culture. The patient experienced multiple relapses of PTB, despite initial clinical and microbiologic response with standard therapy. Upon failure of a second line regimen including levofloxacin and amikacin, sputum cultures again grew susceptible M.tb. despite adequate plasma levels of antimycobacterial agents. A plasma 25-hydroxyvitamin D (25(OH)D) level of 7 ng/mL diagnosed vitamin D deficiency, and the patient was treated with 50,000 IU of ergocalciferol orally thrice weekly for 8 weeks. She responded with weight gain, radiographic improvement, negative sputum cultures at month 15 of overall treatment, and a repeat 25(OH)D level of 81 ng/mL. No adverse events were observed. Discussion: We present a case of vitamin D deficiency in a patient with relapsed PTB, safely treated with 50,000 IU of ergocalciferol thrice weekly for 8 weeks. With correction of deficiency, the patient demonstrated improved microbiologic and clinical outcomes, with negative sputum cultures and improved TB symptomatology. Our clinical experience and review of relevant literature is in support of the emerging evidence of vitamin D as a potential anti-mycobacterial agent. Further studies of vitamin D as an adjunctive therapy in TB treatment are needed. ## **Medical Education and Medical Ethics Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 147 INSTRUCTOR DIRECTED LEARNING OF RHEUMATOLOGY IS SUPERIOR TO STUDENT SELF STUDY P.F. Bass1, S.M. Berney1, C. Mitchell2, A. Sittig1, R. Arora1 * 1LSUHSC-Shreveport, Shreveport, LA and 2MedStudy, Colarado Springs, CO*. #### Purpose of Study Medical curriculum reform implemented by the LCME stresses self-instruction as crucial to lifelong learning, but decreases didactic teaching time and exposure to individual faculty members. We hypothesized a didactic experience with a mentor will improve comfort with certain rheumatologic concepts and improve knowledge retention. #### Methods Used During the IM clerkship, voluntary junior medical students were randomized to either a self learning or a directed learning group. All participants took a 34 question pretest and completed a series of visual analogue scales (VAS) addressing their comfort level with various aspects of rheumatology. Both groups received the Primer on the Rheumatic Diseases, a series of PPT lectures, electronic materials to teach the joint exam and arthrocentesis. The directed learning group had lectures presented to them, met with a Patient Partner (trained to teach the joint exam) and learned joint aspiration using injection models. Both groups underwent a rheumatology standardized patient exam, repeated the pretest VAS and took a post test. #### Summary of Results 73 students participated - 38 in the directed learning (DL) and 35 in the self learning (SL) groups. The DL group improved their pretest to posttest score by an average of 4.7 + 3.9 answers and the SL by 4.0 + 3.6 answers (*P* = 0.4). Additionally, there was no difference between the 2 groups on their standardized patient exam. However, at the end of the course, the DL were 44% more comfortable with rheumatology compared with the beginning as reflected by their VAS while the SL only became 26% more comfortable (*P* < 0.0001). #### Conclusions This study indicates that although direct teaching was not superior to self-instruction when assessing knowledge, the students' direct interaction with an instructor significantly improved their comfort. This data may have long-term implications, because many students and residents choose their ultimate subspecialty based on their comfort with educational concepts and patients. By increasing comfort levels with rheumatology clinical skills and knowledge, a DL approach may increase the number of trainees who eventually pursue rheumatology careers. ### 148 ASSESSING RESIDENT KNOWLEDGE OF INJURY PREVENTION IN CHILDREN T.C. Davis, M. Nichols, K. Monroe *University of Alabama, Birmingham, AL*. #### Purpose of Study The AAP recognizes the importance of counseling patients on injury prevention. No formal resident education program exists. We created a program called IPCA (Injury Prevention and Child Advocacy) to better inform residents about common injury prevention counseling guidelines. Our objective was to determine the best way to convey injury prevention information and what topics residents believe are important for their practice. #### Methods Used After IRB approval, IPCA emails were sent twice monthly for one year. These emails contained five to ten key points regarding specific injury topics. At the end of the year, all our pediatric (and combined med-peds) residents were asked to complete a survey to evaluate the usefulness of the IPCA email format. Results were entered into Microsoft Excel. #### Summary of Results Of the 68 pediatric and internal medicine/pediatric residents, 44 (65%) responded to the survey. All respondents read at least some of the IPCA emails. Of the 93% of residents who did not read all of the emails: reasons given were no time (20%) and emails too long (9%). 45% stated that they liked receiving information by email. Preferred methods of education included interactive cases (75%) and lectures (23%), although board review was suggested as a way to convey information as well; residents were allowed to choose more than one answer. #### Conclusions Residents in our program were pleased with the concept of the IPCA program. Given the importance of injury prevention in pediatric practice, improvements need to be made to the IPCA program to make information more resident-friendly. ### 149 NOVEL PROFESSIONALISM CURRICULUM FOR A PEDIATRIC RESIDENCY PROGRAM R. Dawkins, S. Fogarasi *Louisiana State University, New Orleans, LA*. #### Purpose of Study Designing a curriculum and demonstrating competency in the domain of professionalism is of utmost importance, as it is mandated by ACGME. Effectively teaching professionalism in pediatric residency programs has proven to be a challenging task. Our program designed a novel, longitudinal curriculum that has introduced important themes from the professionalism literature as well as provided our residents with a forum to share their thoughts and experiences about professionalism in a safe, supervised setting. #### Methods Used Due to residents' busy schedules, multiple clinical sites, and a busy cadre of clinical professors, we needed to overcome significant obstacles. We opted to integrate this curriculum into the noon conference time, and to offer it quarterly. We divided all of our residents into groups of ten, spanning all levels of training. Each group is paired with one or two faculty members who went through a faculty development seminar introducing this curriculum. Using cases provided in the "Teaching and Assessing Professionalism: A Program Director's Guide", we aimed to address the following topics: Introduction to Professionalism, Professionalism and Clinical Care, Professionalism and Stress, and Professionalism and Society. Each session opens with a short description of the day's topic. The faculty mentors are given a syllabus with themes for discussion and cases that can be addressed. The residents are encouraged to bring up their own cases and experiences for discussion. Additionally, each resident is encouraged to write a reflective piece that they may chose to share. #### Summary of Results During the first year of this course, participants were asked to write down what they "took away" from each session, which is in the process of analysis. Each year the curriculum for the professionalism small groups will stay the same with the hopes that residents and faculty have the opportunity to continue this dialogue over time. We have already received verbal feedback that both the residents and faculty have found these sessions valuable for their professional growth. #### Conclusions Integrating professionalism longitudinally into our residency program was quite successful. Additionally, this curriculum satisfy's the ACGME's reflective practice requirements. Many residencies could easily implement similar program into their core curriculum. ### 150 PEDIATRIC JUNIOR CLERKSHIP STUDENTS: DO THEY DO WHAT THEY DOCUMENT? DO THEY DOCUMENT WHAT THEY DO? A FOLLOW-UP REPORT N. Humphries, M. Broussard, P.F. Bass *Louisiana State University Health Sciences Center, Shreveport, LA* #### Purpose of Study The primary purpose of this study is to determine if inconsistencies exist between the examination maneuvers and documentation of these maneuvers as documented by junior medical students. An additional purpose is to see whether documentation errors decrease as students progress throughout the clinical 3rd year. #### Methods Used Junior medical students on the outpatient clinic rotation of the Pediatric Clerkship were recorded performing examinations on patients younger than 5 years old with appropriate consent. Each videoed encounter was reviewed independently and results were recorded on a standard physical exam checklist. Exam elements performed incorrectly were also noted on the form. A separate investigator reviewed copies of clinic notes for each patient encounter and recorded results from the clinic note on the checklist Both checklists were compared to determine if any discrepancies between performed physical examination skills and the corresponding documentation existed. #### Summary of Results Twenty-five student-patient encounters have been recorded and reviewed. All encounters have been performed by junior medical students (n = 20) with varying amounts of clinical training. On the 25 videos, 296 physical exam maneuvers were performed; only 73% were documented. There were 302 items documented in the 25 corresponding clinic notes, 28% of which were not clearly performed on the video. The most common elements documented but not performed were eye and neck examinations. The video reviewer did not see any physical exam elements that were incorrectly performed. #### Conclusions No encounters were completely and accurately documented. Limitations include a single-institution study with a small number of encounters. Data are still being collected to determine whether documentation errors decrease as students progress throughout the clinical 3rd year. ### 151 PEDIATRIC PATIENTS ON CHRONIC HOME MEDICATIONS: HOW FREQUENTLY ARE CHRONIC HOME MEDICATIONS CORRECTLY IDENTIFIED AND ORDERED BY ADMITTING HOUSE OFFICERS IN A TEACHING HOSPITAL? A FOLLOW-UP REPORT J.L. LeBlanc, K. Green, M. Broussard, P.F. Bass *Louisiana State University Health Sciences Center, Shreveport, LA* #### Purpose of Study Determine the accuracy with which Pediatric house officers at the Children's Hospital of LSUHSC-Shreveport obtain home medication information and subsequently order daily home medications for pediatric inpatients with chronic illnesses. #### Methods Used Pediatric patients admitted to Children's Hospital of LSUHSC-Shreveport who were taking at least one home medication for at least 30 days for previously diagnosed chronic illnesses were interviewed by a Pharmacist or Doctorate of Pharmacy (PharmD) student within 72 hours of admission to the hospital. The investigators then compared this to the pediatric patient history record completed by the admitting nurse, the resident's admission note, intern's admission note, and all physicians' orders within 24 hours of admission. #### Summary of Results This interim report includes 33 patients (45% females and 55% males). The mean number of medications for each patient was 4 (range 1-12). Of 2754 possible errors, 667 errors occurred (24%). Graph 1 shows the percent error for each group. Compared to the pharmacists, each group made significantly more errors (*P* < 0.001). The resident admit note contained the most errors. There was a significant relationship between the number of medications a patient takes and the number of errors in that patient (*P* = 0.02). #### Conclusions Pharmacists obtain the most accurate medication histories from patients. As the number of medications a patient takes increases, the number of errors by those admitting the patient also increases. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F9.medium.gif) [Figure.](/content/57/1/301/F9) Figure.   ### 152 EVALUATING THE EFFECT OF AN INTENSE ORIENTATION SESSION ON RESIDENT ATTITUDES TOWARD CONTINUITY CLINIC TRAINING S.R. Meenrajan, A. Ketty, O. Petrucelli, S. Nahman *University of Florida, Jacksonville, FL*. #### Purpose of Study To understand the effect an intense orientation session has on resident attitudes towards their continuity clinic training. #### Methods Used The study involved survey and focus group discussions with residents in the Internal Medicine Categorical Program at a University Medical Center. Survey and focus group discussion was held with all residents prior to and 6 months after an intense half day orientation to the Continuity Clinics which included orientation to facilities at the site, clinic staff including pharmacy support, call center and referral coordinators, Electronic Medical Record training and a session on other programs available at the clinic. #### Summary of Results The initial survey and interview was completed by 15 residents and 12/15 had an interest in fellowship training, 9/15 had a positive attitude towards the Continuity Clinic experience. Residents related a number of concerns in the operational part of the Continuity Clinics,difficulty with the electronic medical records, getting patients for follow up, patient no show rates and the support mechanisms at the clinic. Attendance to the orientation was mandated of all residents. The repeat survey and focus group session was attended by 18 residents. 16/18 thought it was helpful in some way with two responses that it was not helpful. The difficult part seemed to be the electronic medical record where new residents thought it was inadequate. The number of residents interested in fellowship was unchanged. #### Conclusions The results of this study seem to indicate that having an intense orientation session to familiarize trainees with the clinic system was viewed as positive by most residents. Residents feel that the session is helpful in handling a number of day to day issues except in the use of electronic medical records. The interest for the majority of residents pursuing Internal Medicine Residency is in subsequent fellowship and not in primary care careers and this was unchanged after the orientation session. Regardless, the orientation session seemed to make the residents adapt faster and had a positive impact on their approach to the clinics. ### 153 IMPLEMENTING A MENTORING PROGRAM IN A PEDIATRIC RESIDENCY S.H. Mennito1,2, J.R. Reigart1 * 1Medical University of South Carolina, Charleston, SC and 2Medical University of South Carolina, Charleston, SC* #### Purpose of Study The Department of Pediatrics at the Medical University of South Carolina developed a formal mentoring program that began in 2007, replacing an advisory program that often did not address the mentoring needs of the residents. This is a description of the methodology involved in implementing a mentoring program into a pediatric residency and initial indications of its success. #### Methods Used Program Focus: Mentors guide academic and overall professional achievement, rather than specific career choices or research direction. Participants: Mandatory participation is required of residents/mentees with voluntary participation from pediatric faculty/mentors. Mentor Assignment: Residents are assigned a mentor with a maximum ratio of 2 mentees per mentor. Faculty Development: Resources are provided to all mentors: an outline of goals and expectations, a checklist of topics to guide meetings, access to resident performance evaluations, and resources from the literature on being an effective mentor. Meetings: The expectation is monthly meetings. The first meeting with a PL1 is initiated by the mentor whereas responsibility for further meetings, and those with higher level residents, is shared between mentee and mentor. Appreciation: The department sponsors social events during the year to celebrate the "Academy of Mentors". Assessment: Resident interviews were performed at the end of the academic year to assess experience and satisfaction with the program. #### Summary of Results 100% of residents identified a mentor who is a member of the pediatric faculty. The number of meetings for the PL1 class (n = 14) ranged from 2-10, median of 3; PL2 class (n = 15) ranged from 0-50, median of 3; PL3/4 class (n = 16) ranged from 0-10, median of 2. 64% of PL1 residents reported the "single best aspect" of the program to be "someone experienced to talk to", 40% of PL2s reported "encouragement/support", and 44% of PL3 residents reported "career advice". #### Conclusions A formal mentoring program with clear goals and objectives can be successfully implemented in a pediatric residency. Benefits may vary for residents at different levels of training. Continued emphasis must be placed on the importance of regular meetings and further assessment is needed as the program matures. ### 154 ENHANCEMENTS TO THE EDUCATIONAL FORMAT OF PEDIATRIC MORNING REPORT AT THE MEDICAL UNIVERSITY OF SOUTH CAROLINA (MUSC) S. Pasala1, D. Mills1, L. Cousineau1,2 * 1Medical University of South Carolina, Charleston, SC and 2Medical University of South Carolina, Charleston, SC*. #### Purpose of Study The pediatric chief residents at MUSC assessed the prior format of morning report and recognized an opportunity to enhance educational productivity and attendance. A needs assessment was performed and multiple, innovative educational and technological strategies were implemented. Evaluation of the effectiveness of these interventions is ongoing. #### Methods Used Our needs assessment process began with an appraisal of the previous format by a dedicated committee of residents and faculty that generated a list of improvement goals. These goals were successfully instituted and included: selection of cases in advance for presentation from different divisions, encouraged attendance from subspecialists, and brief presentations to highlight educational pearls of the cases. Each case is immediately uploaded to an interactive Wiki site, important discussion points are summarized, and direct links to the educational presentations and references are provided. For physicians unable to attend, additional teaching comments may be posted at any time. #### Summary of Results Attendance data comparing the 2007-2008 academic year to that of 2008-2009 is still being compiled. Preliminary data shows mean resident attendance for July-September 2007 to be 30.3% compared to 41.5% for the same time period in 2008. This is a significant increase of 11.2% (*P* = 0.0009). We are currently gathering data on the number of visits to our internet Wiki site to better understand the educational interests of our residents and faculty and the ease of accessibility to case information. #### Conclusions The MUSC pediatric morning report conference has experienced multiple educational enhancements in this academic year. There has been a significant increase in attendance and it is now standing room only. Additionally, the Wiki site provides an expansive, interactive catalog of de-identified pediatric teaching cases. Ongoing assessment will allow better understanding of the benefits these changes have on resident education. ### 155 ROLE OF AN INTERDEPARTMENTAL TEACHING SEMINAR TO FACILITATE COMMUNICATION AND CLINICAL UNDERSTANDING IN PGY-1 RESIDENTS O.M. Petrucelli, T. Morrissey, S. Meenrajan, V. Seeram, Z. Goldman, C. Dave, N.S. Nahman *University of Florida, Jacksonville, FL*. #### Purpose of Study To assess the clinical knowledge of first year residents in the Emergency (ED) and Internal Medicine (IM) departments using pre and post-testing following didactic seminars designed to improve their medical knowledge. To utilize pre and post-course surveys to evaluate the quality of communication between the two groups. #### Methods Used First year residents from the ED (N = 15) and IM (N = 18) attended 12, one-hour, weekly seminars covering common medical knowledge content areas. Pre and post-course multiple choice exams were completed and evaluated using one way ANOVA. At the start and conclusion of the course, participants completed surveys assessing perceptions of the quality of communication between the two departments. The survey consisted of 8 five-point Likert scale (1 = poor, 5 = excellent) questions rating perceptions of communication. Pre and post-course responses were compared using Student's t test. #### Summary of Results We observed a significant improvement in the medical knowledge of the residents (*P* = < 0.001) when comparing mean pre-test (71.58%) and post-course scores (82.90%). However, our study revealed this cohorts perception of their working relationship pre-course (3.81) to post-course (3.98) was unchanged (*P* = 0.72). A similar trend was observed when comparing their perception of the quality of communication [pre-course 3.77; post-course 3.86 (*P* = 0.94)], coordination of care [pre-course 3.84; post-course 3.75 (*P* = 0.54)], and team work [pre-course 3.91; post-course 3.84 (*P* = 0.61)]. #### Conclusions Our study aimed to improve the medical knowledge and communication between two groups of physicians who interface daily in the management of patients. We demonstrated that the seminar significantly improved the medical knowledge of the group; however, no perceived improvement was noted in their working relationship or communication. Our results suggest that it may be too early to identify any long lasting results. We will track this cohort and continue to offer this seminar yearly. ### 156 DECISIONALLY IMPAIRED PATIENTS AS RESEARCH SUBJECTS: ETHICAL, LEGAL & SOCIAL IMPLICATIONS OF SURROGATE CONSENT T.H. Stone *University of Texas Health Science Center, Tyler, TX*. #### Purpose of Study Elucidate federal, state and international laws and relevant ethical principles that pertain to the use of surrogates (or third parties such as proxies or legally authorized representatives) to provide consent to research on behalf of decisionally impaired patients. #### Methods Used Statutes, regulations, court cases and related ethics codes and other legal material of U.S. (federal and state) and international jurisdictions were analyzed to determine and assess their implication for the use of surrogate consent for research involving decisionally impaired patients as subjects of clinical research. #### Summary of Results Select federal, state and international laws address the use of surrogates to provide consent for research on behalf of decisionally impaired patients. Currently, federal regulations and European Union directives expressly defer to state or local laws to determine the precise conditions and limits under which investigators may seek surrogate consent for research and surrogates may exercise consent authority. However, few U.S. states explicitly permit surrogates to make decisions for decisionally impaired patients about taking part in clinical research. Consequently, investigators, IRBs and research sponsors may attempt, as evidenced by investigations conducted by the U.S. Office for Human Research Protections (OHRP), to extrapolate the permissibility of involving decisionally impaired patients in research from other state laws that pertain to surrogate consent to medical treatment generally. Absent direct clinical benefit to subjects provided by proposed research that is consistent with medical practice, state and local laws on surrogate consent to treatment are unlikely to provide surrogates with the legal authority to exercise consent to research on behalf of decisionally impaired patients. #### Conclusions Research institutions, IRBs, and research sponsors should develop and implement specific policies that conform to their applicable state and local laws and that address the use of surrogates to provide consent for research on behalf of decisionally impaired patients. Investigators and IRBs should be provided with appropriate related training and guidance. Model policy guidance and practice pointers are provided for investigators and research review committees for this purpose. ## **Pediatric Clinical Case Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 157 ATP BINDING CASSETTE TRANSPORTER A3 (ABCA3) MUTATION AS A CONSIDERATION IN TERM RESPIRATORY DISTRESS SYNDROME (RDS) L. Barbiero, S. Buchter *Emory University, Atlanta, GA*. #### Case Report KD is a 40 5/7 WGA female born to a 23 year old G2P1 Mexican mother. Birth weight was 2730 grams with Apgar scores of 6,8, and 9. She was grunting and retracting and was admitted to the NICU on CPAP. CBC on admit was normal and she was started on empiric antibiotics. Echo on DOL 1 showed structurally normal heart with bi-directional PDA. CXR showed air bronchograms and hazy lung fields, consistent with RDS. She was intubated on DOL 2 at birth hospital for surfactant therapy and quickly extubated to CPAP. She required re-intubation on DOL 3 for worsening respiratory failure. Progressive hypoxia and hypotension prompted transfer to a regional NICU on DOL 5. At the regional NICU, she required HFOV and iNO. A second dose of surfactant was given on DOL 6 with transient improvement and FiO2 wean. Repeat echo on DOL 6 showed no pulmonary hypertension. She tolerated conventional ventilation and iNO wean. On DOL 7 she had a marked decompensation requiring hand bagging and return to FiO2 of 1.0 on HFOV with iNO at 20 ppm. She had interval worsening of hypotension despite multiple pressors with persistent hypoxia, prompting transfer to a Level IIIC NICU for ECMO evaluation. She continued to have marked hypoxic respiratory failure on HFOV with iNO at 20 ppm. This improved with heavy sedation. CXR continued to display changes suggestive of RDS. This was concerning for surfactant protein deficiency and genetic testing was sent. In the interim, she remained critically ill on HFOV. Viral and bacterial respiratory cultures were negative. Results at 1 month of life revealed normal surfactant protein B and C genes. However, there was a novel gene mutation in the ATP-binding Cassette Protein Member 3 (ABCA3) resulting in a null mutation. ABCA3 mutation is a recently discovered inborn error of surfactant metabolism, joining a rare group of disorders including surfactant protein deficiencies. ABCA3 is primarily expressed in lamellar bodies in type II alveolar cells and is critical in maintaining homeostasis via transport of phospholipids and proteins to the alveolar surface. Loss of function mutations result in a lethal surfactant deficiency in newborns. In cases of recalcitrant symptoms of RDS in a term neonate, one must consider ABCA3 mutation as a potential etiology. ### 158 UNUSUAL CAUSE OF SUBDURAL EMPYEMA IN AN ADOLESCENT K. Bradham, R.A. Connelly *University of South Alabama, Mobile, AL*. #### Case Report BACKGROUND: Otorhinologic infections have been the major cause of subdural empyemas. Common bacterial agents have been 'Streptococcus pneumoniae', nontypable 'Haemophilus influenzae', 'Moraxella catarrhalis' and anaerobes. Nutritionally variant streptococci (NVS) are currently classified as 'Abiotrophia'. Lacking many of the virulence factors found in the other streptococci species, 'Abiotrophia' species have been implicated in 'culture-negative-endocarditis' cases in adults. To the best of our knowledge, 'Abiotrophia' species have not been implicated in cases of subdural empyema in children. CASE SUMMARY: This is a 14 year-old male previously healthy who sustained injury to his face during an altercation. A computed tomography (CT) of the head done during trauma assessment showed only left sinus disease. The patient's symptoms worsened over the next two days with mental status changes. Repeat CT of the head revealed a subdural empyema. Emergency craniotomy was performed and the patient was started on broad spectrum intravenous vancomycin, rifampin, and meropenem. On postoperative day one, the patient was noted to have left-sided hemiparesis. The subdural empyema persisted following neurosurgery as demonstrated by subsequent imaging studies prior to transfer. Cultures from the empyema aspirate revealed a nutritionally variant streptococci ('Abiotrophia' species). The left-sided hemiparesis progressively improved during hospital stay. Rifampin was discontinued after 10 days. The patient was transferred to an inpatient rehabilitation facility for physical and occupational therapy, and completed a 21-day course of vancomycin and meropenem. On follow up outpatient visit three weeks after onset of symptoms, the patient was fully recovered with no remaining neurological deficits; he had full range of motion and intact muscle strength in all extremities. DISCUSSION: To the best of our knowledge, this is the first report of nutritionally variant streptococci-associated subdural empyema described in pediatrics. This report could open the door for future research on this unusual fastidious organisms and the disease processes they can cause. Our patient had a relatively speedy recovery from a disease with otherwise potentially severe long-term neurologic consequences. ### 159 DELUSIONS OF PARASITOSIS IN CHILDREN: A CASE REPORT AND REVIEW OF ETIOLOGY-BASED MANAGEMENT OPTIONS J.C. Carlson1, J.M. El-Dahr1, M.B. Feibelman2 * 1Tulane University, New Orleans, LA and 2Tulane University, New Orleans, LA*. #### Case Report A 10-year old girl, after evaluation by her pediatrician, dermatologist and child psychiatrist, was referred for persistent descriptions of parasites emerging from her body. History was remarkable for atopy and anxiety that had functionally impaired her daily living. Daily shortness of breath, attributed to asthma, was treated with levoalbuterol. The patient denied sensations in association with the parasites, and had no contacts with similar complaints. Physical exam was significant only for xerosis. Microscopy and blood tests were normal except for elevated IgE to tree pollen. Cognitive errors with internally-sustained suggestions were suspected as the etiology of the delusions; treatment of the underlying anxiety disorder was recommended. The patient and her mother were not interested in medications, but did begin psychotherapy. After a period of improvement, psychotherapy was stopped, followed by a relapse of symptoms. Delusions of parasitosis can arise from real sensations in a patient with source monitoring errors, or from suggestions in those rendered susceptible by a primary cognitive condition. In the latter case, suggestions can be sustained by rumination/obsession or by folie impose. In children with obsessive thoughts that sustain the suggestion, treatment of the underlying psychiatric condition is helpful. Folie impose resolves with removal from the environment. For source monitoring errors, treatment of the condition causing the sensation is helpful. Many cases progress to involve both suggestions and source monitoring errors. Patients with a cognitive etiology for delusions often focus on minor skin defects and sensations as evidence of infestation, and generate wounds in an attempt to extract the perceived parasites. Patients with source monitoring errors may develop cognitive errors as well, leading to persistence of the delusion after resolution of the instigating sensation. Determining the primary etiology of the delusions can help to determine the therapy likeliest to help. However, the treatment of patients suffering with delusions remains challenging. The establishment of a therapeutic alliance is hindered by conflicts between a physician's diagnosis and the patient's fixed belief. ### 160 DIFFICULITIES IN DIAGNOSIS IN NOVERBAL, NONAMBULATORY CEREBRAL PALSY PATIENTS T.N. Cauley, K. Savells *University of South Alabama, Mobile, AL*. #### Case Report Diagnoses in nonverbal, nonambulatory, spastic cerebral palsy patients can be met with many challeges. We present a case in which obtaining a thorough history and being attuned to concerns of the caregiver guides you toward a diagnosis. A thirteen year old African American female with past medical history significant for cerebral palsy, seizures, microcephaly, quadriparesis, traumatic brain injury, and constipation presented for evaluation of an abscess on the left knee that developed four days prior. After discussing the treatment plan, the caregiver shared concerns that for greater than one year the patient would hold her head and scream each time she was reclined from sitting to lying position. The patient was content if she remained in the sitting position. The caregiver had discussed this concern with a variety of health care providers over the past year but imaging studies had not been performed since the diagnosis of migraines two years prior. The patient was sent for MRI of the brain and c-spine. The MRI revealed abnormal enhancing extradural soft tissue mass involving the posterior elements at C7, T1, and T2. The radiologist suggested a CT to further explore the mass and surrounding area. CT revealed bony erosion involving the posterior element of the left-sided lamina of T1 and to a lesser degree at T2 which extended into the spinous process at T2 more so than T1. The facet joints, ribs, and vertebral bodies themselves were unaffected. Alignment of the spine was normal. Suprisingly, the caregiver was relieved with the diagnosis of a mass, feeling she finally had an answer to the patients discomfort. The patient was taken to surgery for C7-T2 laminectomy for tumor resection. Resection of the tumor was successful, and the pathology results were benign. Post surgery the patient is completely asymptomatic. This case highlights the importance of listening to our patients and the caregivers so that we can develop an accurate assessment and plan. ### 161 DELETION OF CHROMASOME 22 WITH NEURONAL MIGRATIONAL DEFECT C.M. Cottrill, S. Green *University of Kentucky, Lexington, KY*. #### Case Report A 2 month boy presented to the neurology service with jitteriness. This was felt to be a normal phenomenon. No serum Calcium determination was done. Genetic evaluation was positive for multiple dysmorphic features not characteristic for any specific syndrome. At 4 months, seizures necessitated another neurologic evalustion. The EEG was abnormal and the MRI showed neuronal migrational disorder. At 2 years of age, he was seen by pediatric cardiology and his facies suggested deletion of Chromasome 22 at the q11 locus. This was documented by Fish analysis. His only cardiac abnormality was a right aortic arch. He remained asymptomatic from the cardiac stand point, but continued seizures mandated additional anticonvulsant drugs, and he experienced developmental delay. Because Deletion of Chromasome 22 is a migrational defect of the neural crest cells (ecto-mesenchymal cells) and neuronal migration concerns only ectoderm, observations concerning the co-existence of two migrational defects are noted. In addition, neuronal migrational disorder occurs earlier in gestation than neural crest migration. The embryology of both defects and an attempt to explain their coexistence is discussed. ### 162 CASE REPORT: A 17-YEAR-OLD MALE WITH PSEUDOTUMOR CEREBRI SECONDARY TO PERFORMANCE-ENHANCING STEROIDS TRIGGERING VENOUS THROMBOSIS IN THE BRAIN A.D. DeSena1,2, S. Weimer1 * 1Tulane University Hospital and Clinic, New Orleans, LA and 2Ochsner Clinic Foundation, New Orleans, LA*. #### Case Report Abstract This article is a case report of a 17-year-old male who presented with a headache and blurry vision. He subsequently was noted to have papilledema on a fundoscopic examination and an initial normal MRI and CT of his head; his condition was therefore diagnosed as pseudotumor cerebri. A following MRV of his head revealed venous thrombosis and other investigations revealed an elevated factor VIII level as well as a mutation at the MTHFR locus consistent with an elevated risk for hypercoagulability. In addition, he admitted to steroid usage for purposes of performance enhancement in baseball. The patient's condition eventually improved with acetazolamide and serial lumbar punctures. Steroids have been linked to predisposition to hypercoagulable states, but there are no reports identified by these authors that link performance-enhancing steroids with pseudotumor cerebri as a result of a coagulation dyscrasia. ### 163 PROGRESSIVE ALTERED MENTAL STATUS T.M. Galey1,2, J. Tilelli2 * 1University of Alabama at Birmingham, Birmingham, AL and 2Arnold Palmer Children's Hospital, Orlando, FL*. #### Case Report Two 9-year old males presented to outside hospitals within a six week period, with symptoms of worsening headache, fatigue and malaise. In the 24 hours prior to seeking medical attention, both patients began to have altered mental status. The two patients had full evaluations at their institutions which were normal, including lumbar punctures in which cerbrospinal fluid pleiocytosis was absent. Both patients were transferred to our tertiary pediatric hospital in Central Florida, where over the course of the next 12 hours, they became increasingly more obtunded resulting in a repeat lumbar puncture. Upon close inspection of the CSF, motile ameba were present in large quantities. Both patients were immediately started on IV amphotericin B, azithromycin, fluconazole, and rifampin. They continued to worsen, eventually requiring mechanical ventilation. Within 24 hours of their arrival at our institution, both patients expired, with a diagnosis of primary amebic meningoencephalitis. Primary amebic meningoencephalitis (PAM), first described in 1965, is a rapidly progressive disease caused by Naegleria fowleria. The ameba,found in warm fresh water lakes, penetrates through the cribiform plate, causing rapidly progressive and ultimately fatal neurologic disease. There have only been 9 reports of successful treatment of PAM, with all other cases resulting in death. This presentation will describe two pediatric cases which occurred within a six week period in Central Florida. The discussion will include a description of the vague symptoms of the disease, the techniques used for diagnosis and the treatment regime at our institution, including an unsuccessful attempt at aggressive intracranial pressure management. The presentation will also review the treatment regimes used in the nine documented successful outcomes of PAM. These cases are vital to the practice of medicine in the south, as all nine successfully treated patients received anti-helmith treatment immediately upon their arrival in the emergency room, showing that a high index of suspicion is needed for successful treatment. These cases also illustrate that prevention and education of patients swimming in fresh water lakes in summer is vitally important to prevent more fatal cases of this disease. ### 164 DISSEMINATED BARTONELLA HENSALAE INFECTION PRESENTING AS HISTIOCYTOSIS X E. Grezaffi, B. Estrada *University of South Alabama, Mobile, AL*. #### Case Report Bartonella henselae is the cause of cat-scratch disease (CSD) which has been widely associated with regional lymphadenopathy and fever of unknown origin. Numerous clinical manifestations have been reported. We describe a patient with disseminated B. henselae infection who presented with clinical manifestations suggestive of histiocytosis X. Case presentation: A 3-year old white female presented with subjective fever and areas of inflammation over her scalp and sternum noticed one day prior to admission. Additionally, she had decreased activity and oral intake. Initial skull radiographs revealed parietal and sternal lytic lesions. Laboratory studies revealed leukocytosis, anemia and hypoalbuminemia. Her C-reactive protein and erythrosedimentation rate were elevated. A human immunodeficiency virus antibody and an RPR were non-reactive. A neutrophil oxidative burst assay, myeloperoxidase stain, total complement, flow cytometry, and immunoglobulin concentrations were normal. A Mantoux intradermal test was negative. Imaging studies including CT scans of the chest and brain and a MRI of the spine were consistent with bilateral paravertebral rim-enhancing collections involving bony erosion, multiple splenic and hepatic hypoattenuations, and mottling of the T10 vertebral body. The presence of hepatosplenic lesions raised the suspicion of CSD. Histologic examination of tissue obtained during excisional biopsies of her sternal and skull lesions revealed acute and chronic inflammation. B. henseale DNA was detected by polymerase chain reaction in both tissue specimens. Subsequently, B. henselae IgG and IgM antibodies were reported positive. She received 6 weeks of antibiotic therapy including azithromycin, ciprofloxacin and trimethoprim-sulfamethoxazole. Follow-up imaging revealed complete resolution of the hepatosplenic lesions, osteomyelitis, and soft tissue masses. Discussion: This case of B. henselae infection is unique because of its clinical presentation mimicking histiocytosis X. To our knowledge there is only one previous report of such presentation. This case is evidence that disseminated B. henselae infection should be suspected in patients with subcutaneous masses associated with lytic bone lesions and hepatosplenic abscesses. ### 165 SNORING AS A SIGN OF HEREDITARY ANGIOEDEMA S.E. Joiner1, B. Estrada2 * 1University of South Alabama, Mobile, AL and 2University of South Alabama, Mobile, AL*. #### Case Report Introduction: Hereditary angioedema (HAE) is an autosomal dominant condition presenting in childhood or early adolescence characterized by recurrent episodes of angioedema, not associated with urticaria or pruritis. Case presentation: A 9 year old presented with facial swelling. His mother noticed snoring and drooling the night of admission associated with difficulty swallowing after the patient woke up. This prompted a medical evaluation. The patient had multiple similar facial swelling episodes during the preceding 2 years, with 1-2 episodes per month. The episodes generally lasted 3 days and involved face, hands and feet. These events were not associated with any particular food or allergen and did not present with urticaria or pruritis. Physical exam was significant for facial edema, specifically in the periorbital region, cheeks, and lips. Tonsillar enlargement was noted with minimal space around the uvula. His C1 esterase inhibitor functional level was found to be 2% with (nl > 68%) a C4 of <5 mg/dl (nl 17-52 mg/dl) which was consistent with previously undiagnosed HAE. His edema resolved within 72 hours of hospitalization. Discussion: HAE can be a life threatening condition which has also been associated with sleep apnea. This case illustrates the need to educate caretakers of children with HAE about the importance of sudden development of snoring as a warning sign which may indicate HAE exacerbation. ### 166 SCIMITAR SYNDROME MASQUERADING AS LATE-ONSET PPHN IN A NEWBORN H. Mitchell, A. Kirkpatrick, R. Toms, R. Romp, M. Law, J. Philips *University of Alabama at Birmingham, Birmingham, AL*. #### Case Report This 37 wk 2,649 gm AGA male was born to a 27 y/o mother after an uncomplicated pregnancy. He was vigorous at delivery but was cyanotic without supplemental oxygen. Apgars scores were 7 and 9. He was admitted to the NICU at an outside hospital. A chest X-ray showed diffuse opacities and the initial arterial blood gas showed a pH of 7.21, pCO2 of 54, pO2 of 33, and HCO3 of 20 on 100% oxyhood. He was intubated, given surfactant and weaned to nasal CPAP by 12 hours. By day 8 he was on a nasal cannula at 2 L/min and room air but continued to have labored respirations. An echocardiogram on day 8 showed a small PDA with left-to-right flow and he was given three doses of ibuprofen. An echo on day 10 showed a tiny PDA and a flat interventricular septum consistent with pulmonary hypertension. CT of the chest without contrast on days 8 and 20 showed bilateral pulmonary opacities. A barium swallow on day 13 was negative for a TE fistula. His oxygen requirements began to rise and he went back on CPAP on day 16 and was given another dose of surfactant on day 18. He was reintubated on day 23 for worsening distress; an echo showed a small PDA with right-to-left shunt and pulmonary pressures greater than systemic. He had also recieved several courses of antibiotic therapy without improvement. Oxygen and ventilator requirements continued to increase and he was transferred to our facility. Another dose of surfactant was given and inhaled nitric oxide at 20 ppm and sildenafil were begun. Two further echos were consistent with PPHN and right-to-left ductal shunting. The right pulmonary veins could not be identified on either study. A CT angiogram with contrast and 3D reconstruction showed partial anomalous pulmonary venous return draining the entire right lung and a collateral from the descending aorta to the right lung. Subsequent therapy has included pressors and other cardiac medications. Transcatheter coil occlusion of the aortopulmonary collateral was performed. Recently, the anomalous right pulmonary venous return was corrected and a lung biopsy obtained. The infant remains critically ill but is slowly improving following surgery. The 3D CT reconstructions will be presented to show the remarkable detail and diagnostic utility of this new imaging modality. ### 167 "MY GENTLE GIANT": GORLIN-GOTZ SYNDROME C.L. Moll, G. Yandle *lsuhsc, New Orleans, LA*. #### Case Report Gorlin-Gotz (Nevoid Basal Cell Carcinoma syndrome) is an autosomal dominant syndrome associated with basal cell carcinomas of the skin, odontogenic keratocysts of the jaw, and palmer/plantar pits. People with this disorder are prone to develop multiple neoplasms and are extremely sensitive to radiation. Jaw swelling is often the presenting symptom. We present a case of an 11-year-old African American male with a past medical history of large gestational age at birth, polydactyly, strabismus, asthma, and developmental delay. He presented to his pediatrician with facial swelling and was treated with antibiotics for presumed facial cellulitis. After six weeks of treatment and worsening symptoms, a CT scan of the head/neck revealed a mass in the right maxillary sinus. He was referred for oncological evaluation. Significant admit vital signs included a blood pressure of 149/68 and a weight of 109 kg. Physical exam revealed labile behavior, macrocephaly, small ears, and coarse facial features with asymmetry. A hard, indurated mass was noted within the area of the right maxilla with displacement of the nasal soft tissue. He had scars on the lateral aspects of the 5th digits of his hands and a microphalus. After drainage by OMFS, the facial mass was confirmed to be an odontogenic cyst. Genetics evaluated the patient and stated that macrocephaly with developmental delay can be seen in a number of different genetic syndromes including Gorlin syndrome, which is also associated with odontogenic cysts. A chromosomal microarry was sent for definitive diagnosis and potential micro deletions or gene duplications. DNA testing of PTCH1, the gene for Gorlin syndrome, was also ordered. Gorlin syndrome is due to a mutation in the tumor suppressor gene, PTCH1. Affecting 1 in every 50,000 to 100,000 children, physical findings are variable and commonly do not occur until puberty. 60% have coarse facial features with frontal bossing, macrocephaly, and facial millia. Basal cell carcinomas of the skin occur in 90% of these children. Though rare, death is usually attributed to invasive basal cell carcinomas. Irradiation of these carcinomas intern causes further damage and carcinogenesis in these patients. Further evaluation for possible Gorlin syndrome is essential due to the associated risk of basal cell carcinoma, meduloblastoma and other tumors. ### 168 A TYPICAL HEADACHE IN AN ATYPICAL TUMOR C.L. Moll, G. Yandle *lsuhsc, New Orleans, LA*. #### Case Report Atypical Teratoid/Rhabdoid Tumor (AT/RT) is a rare, aggressive tumor of childhood that occurs in any part of the central nervous system (CNS). AT/RT accounts for 3% of all pediatric CNS cancers and has a 10% survival rate. Since many of these tumors occur in the posterior fossa, children commonly present with headache, emesis, lethargy, and ataxia. Signs and symptoms depend on the location of the tumor. We present a case of a 4-year-old African American female with a past medical history significant for asthma who came to the hospital complaining of headache, emesis, and ataxia. She had presented to her pediatrician 1 week prior to admission with complaints of headache and emesis for 2 weeks. She was given a diagnosis of viral gastritis and sent home. The following week her gait became staggered, and her ability to feed herself declined. Admission lab values and vital signs were stable except for a blood pressure of 135/93. Physical exam was unremarkable and neurological exam was limited due to lethargy and unsteady gait. CT of the head showed a midline 4 cm mixed solid/cystic mass in the posterior inferior fourth ventricle with moderate hydrocephalus. She was transferred to the PICU where her vital signs and mental status declined despite being started on decadron. She underwent emergent external ventricular drainage. On HD#7 she underwent resection of the tumor. Follow up imaging confirmed metastasis to the spinal cord. She remained in the ICU until HD#39 due to multiple medical complications. Cerebral spinal fluid (CSF) cytology and histology of the tumor identified the malignancy to be an AT/RT. AT/RT affects 3 per 1,000,000 children in the United States. Diagnosis is made initially by CT followed by CSF analysis. Surgical biopsy is critical in obtaining a diagnosis, but resection is not curative. One-third of these children have disseminated disease at the time of diagnosis. Though there is no standard therapy, 50% of AT/RT will transiently respond to chemotherapy. Radiation is usually deferred to children greater than 3-years-old and has been known to slightly improve survival. Children with a large tumor, incomplete resection, metastasis, and those younger than 36 months had the worse outcomes. Prognosis is poor with a 2 year survival less than 20%. Main cause of death is disease progression with leptomeningeal spread. ### 169 FAVORABLE OUTCOME IN PEDIATRIC VICTIM OF BIHEMISPHERIC GUNSHOT TO THE BRAIN J. Niebauer, A. Brooks, P. Prabhakaran *University of Alabama at Birmingham, Birmingham, AL*. #### Case Report There is limited literature on pediatric craniocerebral gunshot wounds. Although rare in children, they are increasing in frequency. The majority of deaths from gunshot wounds occur prior to hospitalization. A series of 30 children with gunshot wounds reported a mortality rate of 20%. While bihemisphetric injuries negatively impact prognosis in children, the outcomes tend to be better than in adults with similar injuries. KD was a 14 year old female who presented to the emergency room awake, but incoherent, and nonambulatory, complaining of head and neck pain with no recollection of any injury. Her initial Glasgow Coma Scale (GCS) was 12. She was hemi paretic on the right with a right occipital laceration. Cervical spine radiographs, obtained to rule out cervical injury, showed a frontal lobe bullet fragment. She was intubated for airway protection in view of declining mental status. A noncontrasted head CT showed a bullet that trajected from the right occipital region to the left frontal region, diffuse cerebral edema, and intraparenchymal and parafalcine hemorrhage. Within three hours of admission to the PICU, her GCS decreased to 7T and an external ventricular drain (EVD) was placed. Initial intracranial pressure (ICP) was 25. Medical management consisted of sedation, hypertonic saline, controlled, mild, hyperventilation, and normothermia. Within three days, ICP's gradually decreased to 10 and the EVD was clamped and then removed on hospital day 6. She was extubated on day 5. Her GCS upon extubation was 15, but with persisting right-sided hemiparesis. She was transferred to the floor on hospital day 7 and discharged on day 25. With aggressive physical and occupational therapy, KD's hemiparesis and ability to ambulate improved. At follow-up one month after discharge, KD was ambulating with a walker, with 4/5 strength in the right extremities, normal mental status, and plans to return to school. The initial, post-resuscitation GCS is one of the most important prognostic indicators in children with craniocerebral gunshot wounds. Transventricular and bihemispheric injuries and occipital entry site are poor prognostic factors. Outcomes in children with penetrating head injuries are better than in adults and these patients should be aggressively resuscitated. ### 170 THE TIP OF AN ICEBERG - EPIPHYSEAL OSTEOMYELITIS IN A TODDLER R. Philip, R.D. Smalligan, G. Balasubrahmanyam *East Tennessee State University, Johnson City, TN*. #### Case Report A previously healthy 19-month-old African American boy presented with a 3-day history of inability to bear weight on his left leg. He had been seen in 2 emergency rooms and diagnosed with transient synovitis each time. Further history revealed intermittent low grade fever and pain in the left leg and hip that was relieved with ibuprofen. No history of trauma, other joint involvement, infections, rash, or antibiotic use. PE: afebrile and normal except for the left leg being held in flexion at the hip and knee, pain with hip rotation, and complete refusal to walk. No tenderness on palpation. Labs: normal CBC,CMP,uric acid, LDH, ESR 7, CRP 0.8. Repeated blood cultures were negative which finally grew MSSA. Xray and ultrasound of the leg/hip: normal. MRI: distal left femoral epiphyseal osteomyelitis. Bone biopsy: osteomyelitis which grew MSSA, no tumor. The child did well with 4 weeks of IV nafcillin and physiotherapy. DISCUSSION: This case is an unusual presentation of osteomyelitis in a toddler for several reasons and also reminds clinicians of the importance of taking a thorough history. The history of fever was overlooked in the initial ER visits which likely lowered the suspicion for osteomyelitis. The normal CBC and ESR were also very misleading in this case. MRI or bone scan are two highly sensitive methods of detecting osteomyelitis if suspicion is present. Though reported in some small series, the epiphyseal location of osteomyelitis (most are metaphyseal) in this case is uncommon in children over 15 m of age due to the absence of transphyseal canals. The normal ESR/CRP with abnormal MRI made biopsy essential to rule out the possibility of a chondroblastoma or osteoid osteoma, both of which may resemble a bone abscess. This biopsy must be done with great care due to the close proximity to the growth plate. Treatment of epiphyseal osteomyelitis is typically similar to other osteomyelitis cases including IV antibiotics initially and surgery only if not responding clinically. This case reminds pediatricians that toxic synovitis should be reserved as a diagnosis of exclusion and that osteomyelitis can present in subacute and atypical fashions. ### 171 FECOTHORAX, MECONIUM ILEUS-A CASE REVIEW A. Ramachandrappa, J. Moore *Emory University, Atlanta, GA*. #### Purpose of Study We review the case of a premature infant with an intestinal perforation and stool in the pleural cavity. #### Methods Used Case Review #### Summary of Results A female infant with a birth weight of 1328 grams, born to a 22 year old White G5 P3 woman at 34 weeks 5 days GA, was transferred to us at 2 days of age. Prenatal labs were negative and prenatal care began in the 1st trimester, complications during pregnancy included PIH. Infant was born by c-section due to worsening PIH, severe IUGR, and a biophysical profile score of 2/8 prior to delivery. Apgar scores were 9 and 9 at 1 and 5 min respectively, she was admitted to the NICU secondary to the low birth weight. She was kept NPO overnight, but started having some abdominal distention. On day of life(DOL) 1 baby passed mucus plug and frank blood from the rectum, KUB showed dilated loops, abdomen was progressively increasing in size and was transferred to us for surgical evaluation on DOL 2. On admission she had significant increased work of breathing. X-rays from the birth hospital showed dilated loops and low lung volumes, after further careful review, there was free air noted on x-ray done that morning. Patient was intubated shortly after arrival. On x-ray, there appeared to be a large pleural effusion and there was also a concern for abdominal free air, the cross-table film showed significant free air in the abdomen and radiology noted there may be some tracking into the chest but it was not mediastinal. The patient still had a 100% FiO2 requirement and increased work of breathing at this point, so a needle thoracocentesis was performed on the right chest to tap the effusion. 45 ml of green liquid stool was aspirated with marked improvement in the respiratory status; a chest tube was then placed. Upon exploratory laperotomy of the abdomen a large amount of fluid and stool present in the peritoneal cavity. The majority of the bowel was distended, and a perforation was found in the terminal ileum. A terminal ileostomy and hartman's pouch was done. The stool was hard and consistent with meconium ileus. Further investigation revealed a finger tip sized Right congenital Diaphragmatic hernia (CDH) above the liver, explaining the stool in the chest. #### Conclusions A 34 week IUGR infant with meconium ileus and perforation, with meconium peritonitis and stool in the right pleural cavity secondary to an occult right sided CDH. ### 172 TRANSFUSION RELATED ACUTE LUNG INJURY: CASE REPORT AND REVIEW C. Ranallo1, D. Becton1, A. Mian1, D. Blackall2 * 1UAMS, Little Rock, AR and 2UAMS, Little Rock, AR*. #### Purpose of Study TRALI is a leading, life threatening adverse effect of transfusion resulting in respiratory distress manifested by tachypnea, cyanosis, dyspnea, and/or fever. The purpose of this report is to present a case of TRALI and to enhance clinicians prompt recognition and treatment in order to reduce mortality. #### Methods Used To report a patient with TRALI, which early recognition and aggressive treatment resulted in a favorable recovery. #### Summary of Results A 16-month old boy is newly diagnosed with B-cell acute lymphoblastic leukemia. Physical exam is normal except for mild hepato-splenomegaly with scattered petechiae. Chest radiograph is normal. Central line placement is scheduled for chemotherapy administration. Half an hour prior to surgery, he receives one unit of irradiated, leukocyte-reduced, apheresed platelets. A central line is placed in the operating room without difficulty. During recovery, he has acute cardio-respiratory deterioration (heart rate 165/min, BP 65/42 mm Hg, temperature 37.2 C, respiratory rate 48/minute, oxygen saturation 78% on room air). Examination reveals symmetrically decreased breath sounds and diffuse crackles bilaterally with normal heart sounds and capillary refill. Repeat radiograph demonstrates extensive "diffuse bilateral infiltrates consistent with pulmonary edema." He is intubated and transferred to the intensive-care-unit. There are no laboratory or radiographic evidence of circulatory overload, underlying infection, bacterial contamination of the donor unit, or acute hemolytic or anaphylactic transfusion reactions. A diagnosis of transfusion-related acute lung injury (TRALI) was made. Early recognition and prompt respiratory and hemodynamic supportive measures are the hallmarks of management. Almost all cases require supplemental oxygen. In severe hypoxemia, intubation and mechanical ventilation with relatively high PEEP are necessary. With appropriate timely management, majority of patients with TRALI recover completely within 96 hours, as did the patient presented in this report. #### Conclusions TRALI is a diagnosis of exclusion and should be considered in all patients who develop acute cardio-respiratory symptoms within 6 hours of blood product transfusion. ### 173 BILATERAL CHYLOTHORACES IN A NEWBORN: A CONSEQUENCE OF ENTEROVIRAL INFECTION? D. Reeves1,2, X. Garcia1,2, S. Schexnayder1,2, S. Jones1,2 * 1University of Arkansas for Medical Sciences, Little Rock, AR and 2Arkansas Children's Hospital, Little Rock, AR*. #### Case Report A two month old ex-29-week pre-term newborn presented with respiratory failure, cardiac dysrhythmias, hemodynamic instability, and anasarca; he was subsequently found to have bilateral chylous pleural effusions. Pleural fluid studies revealed an LDH = 237 units/L, triglycerides = 413 mg/dL, a white blood cell count of 5,650 with 86% lymphocytes in the face of persistent peripheral lymphopenia. In addition, the pleural fluid tested positive for enterovirus by polymerase chain reaction. Bronchoalveolar lavage was negative by routine bacterial culture. Initiation of very low fat enteral nutrition (Tolerex ®) was followed by rapid decline in chylous output. The infant developed junctional ectopic tachycardia; echocardiogram and cardiac catheterization were normal. Myocardial biopsy revealed focal interstitial fibrosis with myosite damage without evidence of myocarditis. In addition to cardiac, hematologic, respiratory, and lymphatic involvement, he had a poor clinical adrenal response to stress. His initial cortisol level was 1 μg/dL; this increased to 19.6 μg/dL following cosyntropin administration. Chylothorax is most frequently associated with thoracotomy or other traumatic injury to the thoracic duct. It is rarely congenital, and in such cases it has been described in certain syndromes including trisomy 21 or Noonan's Syndrome or with lymphatic malformations. Chylothoraces associated with enterovirus infection have not been reported. Despite the lack of a definitive diagnosis, the patient has improved clinically with treatment. Chest tube drainage & low fat enteric feeds have proven to be beneficial in the treatment of his chylous effusions. Lymphatic imaging has not been performed to date, and lymphatic anomaly is a possible cause of this infant's bilateral chylothoraraces. We hypothesize that multisystem enterovirus infection and the associated inflammatory response overcame this patient's lymphatic reserve leading to his presentation. ### 174 EMPHYSEMATOUS CYSTITIS AND PYELONEPHRITIS IN AN INFANT L. Rhodes, S. Quinney, R. Toms, J. Philips *University of Alabama at Birmingham, Birmingham, AL*. #### Case Report This 2,895 gm male infant was born at 38 weeks gestation to a 24 y/o hispanic mother who recieved late prenatal care. Delivery was uncomplicated and he was vigorous with Apgar scores of 8 and 9. In the nursery, he was noted to have syndromic features including cleft lip, low set ears with a pit on the lower right ear, short neck, left cheek skin tag and widely spaced nipples. An echocardiogram was done due to the dysmorphic features and showed an interrupted aortic arch, type B with a ventricular septal defect. PGE1 was begun and he was transported to our center for surgical repair. The karyotype was 46XY and the DiGeorge probe was negative. Goldenhar syndrome was suspected. The lesion was repaired, but his post operative course was complicated by bilateral chylothoraces requiring chest tubes and octreotide infusion. Direct bilirubin peaked at 13.2 mg/dl. He remained ventilator dependent. On post operative day 26, "worm" shaped blood clots were passed in the urine. Sepsis and coagulation evaluations were performed and vancomycin and tobramycin were begun. All studies were normal except for the urine culture which grew >100,000 colonies of E. Coli. A renal ultrasound was suggestive for air in the right collecting system and in the bladder wall. Abdominal CT revealed small foci of air in both lower pole renal collecting systems. The child responed to the antibiotics and repeat urine cultures were negative. Unfortunately, he remained ventilator dependent and ultimately died from septicemia. Emphysematous cystitis is an unusual form of urinary tract infection, usually seen in adults with diabetes. We have been unable to find reports of this entity in infants and therefore report this case to inform the pediatric community. Renal ultrasound and CT images will be presented showing the air collections. ### 175 FULMINATE NEONATAL CARDIORESPIRATORY COLLAPSE CAUSED BY COXSACKIEVIRUS B1 MYOCARDITIS L. Wall1,2, L. Tran1,2, J. Surcouf1,2, A. Sanzone1,2, D. Albrecht1,2, R. Craver1,3 * 1Children's Hospital, New Orleans, LA; 2Louisiana State University Health Sciences Center, New Orleans, LA and 3LSU Health Sciences Center, New Orleans, LA*. #### Case Report A 35 week gestational age female with fatal coxsackie B1 myocarditis is reported. The infant was born by cesarean section due to persistent fetal tachycardia and severe maternal abdominal pain. Tachypnea developed on day of life 1 and she was transferred to the NICU. Labs were normal and blood cultures were obtained. On day 3, apnea and bradycardia occurred and antibiotics were added. In subsequent days, she developed fever, bandemia, DIC, jaundice and hepatitis. Viral cultures were obtained and acyclovir was added. Respiratory distress resolved completely for 48 hours until day 7 when she developed brief apneic episodes. Stimulation with high flow nasal cannula and an apnea mattress produced resolution of symptoms until fulminate, fatal cardiorespiratory collapse occurred 2 hours later. Autopsy demonstrated acute myocarditis and meningoencephalitis, with coxsackie B1 recovered from cultures of heart, liver, lung, and spinal cord. The CDC recently reported an increased level of coxsackie B1 activity associated with severe neonatal disease (MMWR,57:20). While enteroviral infection is common in infants, onset less than 7 days of life causes severe illness (Chen-Chia,1998). Clues that raise suspicion of enterovirus infection include maternal symptoms, seasonal distribution (summer), and lack of risk factors for bacterial infection. Maternal severe abdominal pain has been associated with enteroviral infection. This mother also experienced post-partum fever, oral ulcers, and later developed vesicular lesions on the hand. For diagnosis, PCR is sensitive, specific, and relatively rapid compared to culture. Treatment consists of supportive care, although IVIG has been used with little evidence. An anti-enteroviral drug, pleconaril, is currently in phase 2 clinical trials in neonates. As this case demonstrates, signs of life-threatening complications, such as myocarditis, may be subtle and nonspecific but may lead to rapid death. A high index of suspicion is necessary for rapid diagnosis of enterovirus and to identify complications as they arise. ### 176 TITIS MEDIA GONE AWRY - LATERAL SINUS THROMBOSIS IN ACUTE OTOMASTOIDITIS T. Yohannan, G. Balasubrahmanyam, RD. Smalligan *East Tennessee State University, Johnson City, TN*. #### Case Report A previously healthy 5-year-old boy presented with five days of cough, intermittent fever, earache and right ear discharge. P/E: febrile, irritable boy with anteriorly displaced right pinna and obliterated retroauricular fold. The right TM was perforated and had purulent discharge. There was mastoid tenderness with overlying erythema and fluctuance. The remainder of the exam was normal. Labs: WBC 19,000 with left shift. Temporal bone CT scan showed otomastoiditis. Ear drainage cultures grew S. pneumoniae. He was started on vancomycin and ceftazidime and ENT placed a myringotomy tube. In spite of initial improvement, on day 5 the patient developed abnormal eye movements so an EEG was ordered. The EEG showed focal cerebral dysfunction in right hemisphere prompting an MRA which showed a right transverse venous sinus thrombus extending to the right sigmoid sinus. He stabilized and went home on day 8 with 4 weeks of ceftriaxone and 12 weeks of enoxaparin and did well. Discussion: While acute otitis media (OM) with perforation is seen routinely by pediatricians, mastoiditis is less common, occurring in only 2% of children with OM. Intracranial complications of mastoiditis are rarer, with lateral sinus thrombosis representing a small percentage of such complications in children. Although lateral thrombosis is classically described as presenting with "Picket Fence" fevers and overt cranial nerve palsies, symptomatology can be more subtle as in our case. Etiology is due to direct extension of infection from the mastoid to the sigmoid sinus or thrombophlebitis of small veins in the middle ear extending to the sigmoid sinus. Resistant strains of S. pneumoniae are often implicated in the protracted clinical course of these patients. Treatment of this potentially life-threatening condition includes IV antibiotics, myringotomy tubes and anticoagulation. Our patient's atypical presentation of lateral sinus thrombosis in the setting of mastoiditis may have been due in part to partial masking of the condition by prompt use of antibiotics and pressure reduction by ENT surgery. It is imperative for pediatricians to maintain a high level of suspicion of serious complications of otomastoiditis when any unusual neurologic signs or symptoms occurs in children during treatment. ## **Perinatal Medicine Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 177 A SPECTRUM OF PHENOTYPICAL EXPRESSION OF NEU-LAXOVA SYNDROME: THREE CASE REPORTS AND A REVIEW OF THE LITERATURE W. Coto-Puckett1, E. Gilbert-Barness2,5,6, H. Robinson3, T. Stuart4, B. Shehata4 * 1Emory University, Atlanta, GA; 2University of South Florida and Tampa General Hospital, Tampa, FL; 3Akron Children's Hospital, Akron, OH; 4Emory University, Atlanta, GA; 5University of South Florida and Tampa General Hospital, Tampa, FL and 6University of South Florida and Tampa General Hospital, Tampa, FL*. #### Case Report Neu-Laxova syndrome is a rare autosomal recessive disorder characterized by severe intra-uterine growth restriction (IUGR), extreme microcephaly, marked edema with skin restriction, ichthyosis, craniofacial anomalies, limb deformities, and a spectrum of central nervous system malformations. Less than 70 cases have been described since the first report in 1971. To this day the etiology and genetic basis remains unknown. Consanguinity in four families has been reported. Some authors have postulated the syndrome to be a form of neuro-ectodermal dysplasia, while others suggest that it is a malformation syndrome secondary to severe skin restriction. Although the outcome of this syndrome is lethal, a single case of longer survival (6 months) has been reported. The majority of cases are stillborn or die shortly after birth. Thus, it is clear that Neu-Laxova exhibits a spectrum of disease, with varying degrees of phenotypic expression. We are presenting three new cases of Neu-Laxova syndrome with detailed gross and microscopic post-mortem findings displaying the vast spectrum of this rare syndrome. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F10.medium.gif) [Figure.](/content/57/1/301/F10) Figure.   ### 178 NEONATAL PAIN ASSOCIATED WITH CHEST TUBES: THE NEO-PACT STUDY D. Dannaway, A. Aguirre *Oklahoma University Health Sciences Center, Oklahoma City, OK*. #### Purpose of Study The antiquated idea that newborn infants are incapable of feeling pain has long gone by the wayside. The important questions now facing clinicians concern ways to minimize pain in the newborn. Term and preterm babies sometimes need to undergo invasive procedures as part of their care. One of the most invasive procedures performed on infants is chest tube placement. Several adult studies have identified significant pain and discomfort associated with placing and keeping chest tubes. Some studies have discussed the pain associated with chest tube maintenance in older children; very few have looked at this process in the neonatal population, and there are no studies which describe the level of pain or discomfort associated with an indwelling chest tube among neonates. This study, through a retrospective chart review, will report on the pain scale scores associated with in-dwelling thoracostomy tubes and look at the effectiveness of pain-relieving measures in infants with these tubes. We hope that this will foster future studies that will further our understanding of pain prevention and relief for invasive procedures in this vulnerable population. #### Methods Used This is a retrospective chart review comparing the EDIN (Échelle Douleur Inconfort Nouveau-Né)pain scale scores before and after placement of chest tubes in infants less than two months of age. EDIN scores prior to and after chest tube placement will be recorded and compared via a Wilcoxon Signed Rank test. #### Summary of Results Pending #### Conclusions Pending ### 179 HEAVY METALS IN BLOOD TRANSFUSIONS IN EXTREMELY LOW BIRTH WEIGHT INFANTS M. ElAbiad *University of Tennessee, Memphis, TN*. #### Purpose of Study To calculate the theoretical incidence of lead (PB) or mercury (Hg) toxicity due to blood transfusions in extremely low birth weight (ELBW) infants. #### Methods Used Extremely low birth weight (ELBW) infants, birth weight of ≤1000g, were evaluated for the number of PRBC transfusions they received during their entire hospitalization. A weekly theoretical Pb load received during the first week of life was calculated based on the following assumptions: 1)30% of all PRBC transfusions given during the entire hospitalization (N) are given during the first week of life, 2)Pb content in PRBC is 3.5 times that of whole blood, 3)10 ml/kg as the volume of PRBC given per transfusion, and 4)Pb or Hg content in the whole blood of an adult blood donor is the same as that of the average general population (H). Hence 0.3 * N PRBC transfusions per hospitalization*10 ml blood/kg *3.5 * H mcg/dl= mcg/kg/week Pb load given during the first week of life. This Pb dose was then compared to the provisional tolerable weekly intake (PTWI) dose set by the WHO. For Hg, we calculated a load given with each PRBC transfusion. Hg content in PRBC is twice that of whole blood. We also assumed that Hg levels in childbearing-age women reflect average general population Hg levels. So for Hg load estimation the formula is 10ml blood/kg\*2\*H mcg/L= mcg/kg/transfusion. This calculated load was compared to current daily oral Reference Dose (RfD) set by the US Environmental Protection Agency. #### Summary of Results In the years 2005 and 2006, there were 258 patients with a birth weight of ≤1000g. All received one or more PRBC transfusions. There were a total of 2122 transfusions from 208 PRBC units. The minimum number of transfusions from a single PRBC unit was 5. Based on the outlined formula, there were 50 infants (19%) who potentially received a toxic Pb dose based on the average general population whole blood Pb level of 1.64 mcg/dl. Based on a prevalence Hg level ≥ 6.04 mcg/L in 5% in women of childbearing-age, a minimum of 52 blood transfusion procedures gave a Hg load above the RfD. #### Conclusions Pb and Hg toxicity in ELBW infants as a result of blood transfusions may be common. There is a need to evaluate the true incidence of this possible toxicity by testing PRBC units for Pb and Hg content before being cleared for transfusion in ELBW infants. ### 180 DIFFERENCES IN PROPORTION OF DEATHS DURING WEEK DAYS VS. WEEKEND DAYS IN VERY LOW BIRTH WEIGHT INFANTS M. ElAbiad, A. Talati, R. Dhanireddy *University of Tennessee Health Science Center, Memphis, TN*. #### Purpose of Study Background: In a level III academic NICU the staffing pattern changes with presence of more physicians and NNPs during the day shift compared to evening or night shifts and on weekdays compared to weekend days. Whether there are any differences in number of deaths due to changes in staffing pattern remains unclear. We sought to review our database to determine if the proportions of deaths vary at different times. Objective: To determine the proportion of deaths in a VLBW infant population based on 1) working shifts of a day (day vs. evening vs. night) 2) weekdays compared to weekend days. #### Methods Used Data were extracted from a data bank system to include all infants who died in the 10 year interval (1998-2007). There were three shifts in a 24 hrs period: 7a-3p, 3p-11p, and 11p-7a. The numbers of deaths were compared between shifts. It was also compared between weekend and non weekend days. Chi-square test was used to detect any statistical difference between expected and observed results. #### Summary of Results We had 10980 infants admitted in this 10 year period of which 2296 were VLBW. Out of 459 deaths, 367 (79.9%) were VLBW. The average mortality rate for these VLBW infants was 161 per 1000 live VLBW births (range 116-224). The observed proportions of deaths were 28.7 % during the day shift, 39.4% during the evening shift, and 31.9% during the night shift; *P* = 0.4. There was a statistical difference between expected and observed mortality on weekdays (106%) compared to weekend days (85%); *P* = 0.04. #### Conclusions In our NICU, the trend of the mortality rate for VLBW infants has not significantly changed over a 10 year period. With regards to time of death, there was no significant difference between day, evening, or night shifts. However, the proportion of deaths observed during weekdays was higher than expected compared to the weekend days. ### 181 OPIOID-DEPENDENT NEONATAL ICU PATIENTS: TAPERING WITH METHADONE M.A. Gervase1, A.L. Potts2, B.S. Carter3, * 1Duke University Medical Center, Durham, NC; 2Vanderbilt University Medical Center, Nashville, TN and 3Vanderbilt University Medical Center, Nashville, TN*. #### Purpose of Study Methadone is used to taper opioid-dependent patients who receive intravenous (IV) fentanyl for post-operative pain, or who are on ECMO, or high-frequency ventilation in the NICU at Vanderbilt. The purpose of this study was to investigate the dose and duration of methadone treatment when a scheduled weaning protocol for methadone was used. #### Methods Used A retrospective analysis of methadone use in the NICU during a 6 month period was conducted. All study subjects had received >3 days of IV fentanyl. A 12-day tapering schedule for methadone was prescribed and evaluated. The primary outcome was the presence of withdrawal symptoms (determined by a modified Finnegan score) and subsequent methadone dose escalation. Additional outcomes included duration of methadone taper, total number of preceding days and dosing of fentanyl, physician compliance with the tapering guidelines, and hospital length of stay (LOS). #### Summary of Results Of 55 potential study subjects, 36 contributed to the data. Exclusions included some patients who resumed IV fentanyl or morphine. Of the 36 subjects, 28% required a dose escalation of methadone during their scheduled taper. These escalations were not related to the type of surgery performed. The median duration of fentanyl infusion prior to receiving methadone was 15 days and maximum dose 5.9 +/- 3.4 mcg/kg/hr. The median number of days on methadone was longest in those subjects who had received IV fentanyl for >15 days. Subjects requiring a methadone dose escalation also had a longer median duration of methadone treatment (17 vs. 14 days). Physician compliance with methadone tapering guidelines was 94%. The overall hospital LOS was not affected by methadone treatment. #### Conclusions This prescribed short methadone tapering schedule was found to be effective and did not affect overall hospital LOS in this patient group. Longer treatment and higher dosing with IV fentanyl was associated with longer treatment with methadone, but not necessarily with a requirement for dosing escalation. Further studies evaluating neonatal methadone pharmacokinetics and long-term neurodevelopmental outcomes for treated patients are needed. ### 182 COMPARISON OF A LARGE ENTEROCOLITIS CLUSTER TO NEC CASES FROM OUR LEVEL III REGIONAL NICU DATABASE REVEALS THAT NEC COMMONLY PRESENTS WITHIN LYMPHOCYTOSIS-ASSOCIATED CLUSTERS P.V. Gordon, S. Thibeau, C. Pennier, H. Ginsberg, V. Lunyong, M. Cortez *Ochsner, New Orleans, LA*. #### Purpose of Study We considered enterocolitis in 10 neonates with > Bell's stage I NEC occurring within a three week time period. Ninety percent of these patients were tolerating full feeds upon presentation, most were on breast milk, and most demonstrated lactose intolerance upon re-feeding. Lymphocytosis and thrombocytosis were common features at presentation and two infants developed skin findings consistent with enterovirus-16. Three infants progressed to stage II NEC, one progressed to stage III NEC then died. We hypothesized that NEC presenting with lymphocytosis has clinical characteristics similar to those in this outbreak. #### Methods Used We performed a retrospective cohort review of all cases of NEC > Bell's stage II within our regional level III C database over the past 6 years not including the recent time period of the enterocolitis outbreak. We captured birth weight, gestational age, day of onset, feeding history (when available), CBC data, surgical management, and outcomes. NEC with lymphocytosis was defined as >40% lymphocytes in the 48 h surrounding the time of diagnosis. #### Summary of Results 44 cases of NEC were identified out of 2094 admits (2.1%). NEC with lymphocytocis was found to be abundant (56.8%) and to have a stronger relationship with gestational age than NEC without lymphocytosis (based on the day of onset). This cohort also contained a higher percentage of infants known to be on full feeds prior to presentation (60% versus 11%, *P* < 0.01)). In addition, NEC with lymphocytosis and thrombocytosis showed improved mortality compared to NEC with lymphocytosis and thrombocytopenia (75% versus 38% mortality, *P* < 0.05). Finally, NEC with lymphocytosis occurred in more than twice as many temporal clusters than NEC without lymphocytosis in this single center study (7 versus 3). #### Conclusions We demonstrate that NEC with lymphocytosis shares many of the same characteristics found within the enterocolitis case series, including delayed timing of onset, dichotomized outcomes linked with thrombocyte homeostasis, occurrence in clusters, and a predilection for infants on full feeds. These observations suggest much of NEC in our institution might be triggered by viral agents and form the foundation for a national database study now underway. ### 183 USE OF PULSE OXIMETRY AS A SCREENING TOOL TO DETECT CONGENITAL HEART DISEASE IN ASYMPTOMATIC NEWBORNS B. Harden, T. Wall, W. Johnson, R. Schelonka *University of Alabama at Birmingham, Birmingham, AL*. #### Purpose of Study Neonatal screening protocols aim to detect underlying disease at the earliest recognition so that prompt and appropriate medical intervention can be initiated, thus reducing or preventing associated morbidity and mortality. This study reviewed the use of pulse oximetry as a screening test in newborns to detect congenital heart disease. The objective of this study was to determine whether pulse oximetry detects newborns with congenital heart disease that have no abnormalities on physical exam and no clinical signs that would suggest underlying heart disease. #### Methods Used The retrospective study was performed in a large urban hospital in central Alabama between September 1, 2006 and August 28, 2008. Neonates born at ≥36 weeks estimated gestational age and a postnatal age of 0 to 4 days were screened with pulse oximetry prior to discharge. Neonates with pulse oximetry readings <96% were referred for Pediatric Cardiology evaluation and echocardiography. Newborn nursery and cardiology records were reviewed to determine the reason for evaluation for congenital heart disease. #### Summary of Results There were 6,249 admissions to the newborn nursery during the two year study period. Of these, 86 (1.37%) newborns received cardiology consultation for various reasons. Four infants were diagnosed with critical congenital heart disease based on physical exam findings, including 3 with coarctation of the aorta and 1 with double outlet right ventricle. None of these diagnoses were initiated by routine pulse oximetry. The remaining 82 newborns that were evaluated by cardiology were found to have either normal cardiovascular anatomy or physiologically insignificant echocardiogram findings. Only one of these 82 newborns was referred for cardiology evaluation because of low oxygen saturation. There was no documented reason for cardiology consultation for 4 newborns. #### Conclusions All newborns diagnosed with critical congenital heart disease were initially detected based on physical exam findings. The addition of routine pulse oximetry screening did not add to the recognition of congenital cardiovascular malformation in infants with normal physical examinations. ### 184 WHAT'S WRONG WITH THIS BABY'S LIVER… J.C. Hisey, A. Gong *UTHSCSA (University of Texas Health Science Center San Antonio), San Antonio, TX*. #### Case Report We report a case of a late preterm infant who presents with nonspecific symptoms such as apnea, feeding intolerance, and abdominal distension that progressed to liver failure and disseminated intravascular coagulation. Initial evaluation negative for infectious and metabolic disorders but possibly consistent with neonatal hemochromatosis (ie. elevated iron deposition). However, the infant's elevated liver function tests were not compatible with that diagnosis. Team was considering implementation of treatment for neonatal hemochromatosis when viral cultures became positive for Echovirus 11. The differential diagnosis for laboratory findings consistent with hemochromatosis is: 1) neonatal hemochromatosis 2) Δ4-3-Oxosteroid 5β-reductase deficiency 3) Echovirus 4) CMV. All have relatively high quantities of iron in liver tissue. Review of the literature finds that our patient fulfills the clinical picture of Echovirus 11, especially considering that the infant's mother presented initially with abdominal pain. Echovirus 11 causes a wide spectrum of clinical disease, ranging from asymptomatic infection to death. Our patient presented with nonspecific signs that progressed to needing extraordinary supportive care but ultimately did well. Enteroviral infection should be in the differential diagnosis whenever infants present with nonspecific signs that lead to decompensation. Evidence has shown that enteroviral infections can disseminate within a nursery and proper preventative precautions should be taken. ### 185 FIRST DAY FATAL POMPE DISEASE A.C. Mullins, L.D. Young-Gaylor, D.R. Shanklin *University of Tennessee, Memphis, Memphis, TN*. #### Purpose of Study Pompe disease (GSD IIa - autosomal recessive lack of acid maltase or α-glucosidase [EC 3.2.1.20] has been described as: "…always fatal, usually within two years after birth. Affected children appear healthy at birth, but heart size and EKG are marginally abnormal (Nelson, *Textbook of pediatrics*, 11th ed., 1979, p. 537)." The FDA recently approved specific medication, alglucosidase alfa (Myozyme©), which modulates myocardial storage of lysosomal glycogen. First day presentation of Pompe disease is not well recognized and is a challenge to enzyme replacement therapy, a reason for vigorous antenatal diagnosis. #### Methods Used We report autopsies on two term infants dying 3.3 and 8.0 hours after birth. #### Summary of Results A male infant BW was 3780 g. Mother 36 y, gr 9, p 8, no weight gain after 33 weeks; vaginal delivery; Apgar scores 0/1. An enlarged heart was noted after birth; heart rate could not be maintained. Cardiac consult was requested for possible anomalies but the infant died abruptly at 8.0 hours. The heart weighed 103 g at autopsy; lysosomal glycogen was in myocardium, liver, skeletal muscle, brain. A female infant BW was 3550 g. Mother 34 y, gr 5, p 1, sab 1, a prior SIDS infant, prior preeclampsia, ectopic pregnancy and adnexectomy. Apgar scores 8/9; infant was in the well baby nursery and was found lifeless at 3.3 hours. At autopsy the heart weighed 32.5 g, a 50% increase, with myofiber hypertrophy. Lysosomal glycogen storage was in myocardium, liver, skeletal muscle, brain, adrenals. #### Conclusions Pompe disease is rare, estimated prevalence from 1:40,000 to 1:300,000 births. Potential prenatal yield from typical obstetrical screening methods (amniocentesis, chorionic villus biopsy) is low, considerably less than current rates of complication from these procedures. The activity of acid α-glucosidase in blood spot tests [*Clin.Chem.* 2001;47:1378-1383] is intermediate for heterozygotes when screened for adult or late onset GSD IIb. To our knowledge this method has not been used in prenatal screening. If the mother is a carrier in midgestation then the father should be tested to determine fetal risk. This can also be done before the usual interval for amniocentesis and may be critical should midgestational sonography suggest fetal cardiac emlargement. ### 186 CASE REPORT OF 17Q23.2 DELETION: A NEWBORN WITH SEVERE HYPOXEMIA R.M. Patel, W.R. Sexson *Emory University School of Medicine, Atlanta, GA*. #### Case Report A 2260 gram female infant at 36 weeks and 5 days gestation presented with respiratory distress following a vaginal delivery. APGAR scores were 4, 5, and 5 at 1, 5 and 10 minutes respectively. The infant was intubated in the delivery room. She required an inspired oxygen concentration of 100% along with moderate inspiratory pressures. Arterial blood gas on admission had a pH of 6.7 with pC02 87mmHg, p02 15mmHg and base deficit of 15. Chest radiograph demonstrated bilateral pneumothoracies. Oxygenation did not improve after chest tube placement with pre- and post-ductal oxygen saturation remaining below 30%. Surfactant was administered. The infant was placed on high frequency oscillator ventilation with initiation of inhaled nitric oxide. An echocardiogram noted pulmonary hypertension and patent foramen ovale with right to left shunting. No other cardiac anomalies were identified. Phenotypically, the baby did not appear dysmorphic other than being small for gestational age. Despite treatment for pulmonary hypertension, oxygenation did not improve. The infant developed refractory metabolic acidosis, persistent bradycardia and expired at 16 hours of life. Autopsy findings noted the pulmonary trunk draining directly into the aorta, with small pulmonary arteries and veins and pulmonary hypoplasia. An area of focal colonic stenosis with dilatation of more proximal colon was also seen. Chromosome microarray analysis with confirmatory fluorescent in-situ hybridization demonstrated an interstitial deletion of the long arm of chromosome 17 involving band q23.2. The deletion was 1.46 megabases in size. We report a rare chromosomal deletion associated with lethal congenital anomalies. Autopsy findings suggest that persistent hypoxemia was due to restriction in pulmonary blood flow, hypoplastic lungs and large shunt circulation through a unique vascular connection. Deletions in the region similar to our patient have been shown to cause various heart defects in mice. To our knowledge, only 6 prior cases with similar deletions (17q21-24) have been reported in the literature, 3 of which noted congenital heart defects. The 17q23.2 region may represent an important locus for cardiovascular and pulmonary development. Chromosomal analysis may be beneficial in non-dysmorphic patients with similar clinical course. ### 187 SWALLOW-BREATH INTERACTIONS DURING NONNUTRITIVE SUCK AMONG LOW-RISK PRETERM INFANTS AND INFANTS WITH BRONCHOPULMONARY DYSPLASIA E. Reynolds1, D. Grider1, R. Charnigo2, P. Vijaygopal3, A. Patwardhan3 * 1University of Kentucky, Lexington, KY; 2University of Kentucky, Lexington, KY and 3University of Kentucky, Lexington, KY*. #### Purpose of Study Previous authors have shown changes in suck-swallow-breath rhythms during infant feeding related to the presence of bronchopulmonary dysplasia. Altered swallow:breath interactions (Sw:Br) during nonnutritive suck (NNS) have been less well described. #### Methods Used Low-risk preterm (LRP) infants and infants with bronchopulmonary dysplasia (BPD) were studied for 1 minute of NNS. Patients were instrumented as follows: 2 acoustic detectors for cervical auscultation, a naso-pharyngeal tube to measure swallow pressure, a catheter placed through a pacifier to measure suckle pressure, a thermistor at the nares to measure airflow, a chest band to measure thoracic motion and a pulse oximeter. 16 LRP and 14 BPD infants were studied weekly for a total of 35 LRP studies and 24 BPD studies. 184 LRP and 110 BPD swallows were noted. Sw:Br were classified as central apnea (CA), obstructive apnea (OA) and attenuated respiration (AR). #### Summary of Results Among LRP swallows, 39.7% were AR, 29.9% were OA, and 30.4% were CA. Among BPD swallows, 38.2% were AR, 44.5% were OA, and 17.3% were CA. There was no significant difference between LRP and BPD with respect to the frequency of AR (*P* = 0.8810). There is a significant difference between LRP and BPD with respect to the frequency of OA (*P* = 0.0333). The odds of OA is 49% smaller for LRP. This conclusion persists even after we control for birthweight (BWT), gestational age (GA), and day-of-life (DOL) (*P* = 0.0140, odds of OA is 62% smaller for LRP). There is a significant difference between LRP and BPD with respect to the frequency of CA (p = 0.0344). The odds of CA is 128% larger for LRP infants. However, rigid statistical significance is lost when controlled for BWT, GA, and DOL (p = 0.0581, odds of CA = 155% larger for LRP infants). #### Conclusions Sw:Br during NNS are different between LRP and BPD infants. However, some of these differences are lessened when controlled for BWT, GA and DOL. The clinical relevance of these differences requires further investigation by comparing long-term developmental outcomes. This work was funded by the NICHD Grant 5K23D05081-02. ### 188 THE EFFECTIVENESS OF NEONATAL RESUSCITATION PROGRAM (SPANISH VERSION) IN THE NEONATAL OUTCOME IN A LEVEL III NEONATAL INTENSIVE CARE UNIT IN PUERTO RICO A. Rivera, J. Rivera, I. Garcia, L. Garcia, M. Valcarcel *University of Puerto Rico, Medical Science Campus, San Juan, PR*. #### Purpose of Study Improve competence in individuals,providing the Neonatal Resuscitation Program (NRP)training and improve neonatal outcome #### Methods Used In July 2006,training in NRP was established in University Pediatric Hospital and District Hospital.Personnel involved:nurses,respiratory therapists,pediatric and obstetric-gynecology residents and pediatricians.This is an observational study performed using data from the Vermont Oxford Network forms collected from patients admitted in our NICU.The data include short-term outcomes: admissions temperature,Apgar score and mortality.The long-term outcomes:Bronchopulmonary dysplasia (BKP),Retinopathy of prematurity (ROP),Intraventricular hemorrhage (IVH),length of stay and survival. Variables were compared among two groups:prior NRP and post NRP periods.The pre NRP group include neonates admitted during the period of January 01,06 to June 30,06.The post NRP group include neonates admitted from October 01,07 to March 31,08. #### Summary of Results Study included 384 patients.When matched by gestational age and weight groups were reduced to 131 each.In the short term outcome variables,no changes were found,except for the use of epinephrine in the delivery room,showing an increased after training which is statically significant. Long term outcomes BKP and ROP were importantly reduced but there was an increased in IVH with *P* value of 0.0004 #### Conclusions This syudy shows that training personnel with adequate resusitation skills will improve neonates important long term outcome. View this table: [Table17](/content/57/1/301/T17) ### 189 PRETERM EXPOSURE PATTERN ALTERS IMMUNOLOGICAL PATTERN, AN INTERIM ANALYSIS; PRELIMINARY DATA D.S. Shah1, S. Nandakumar2, G. Balasubrahmanyam1, S. Chilakala1, M. DeVoe1, U. Kumaraguru2, * 1East Tennessee State University, Johnson City, TN and 2East Tennessee State University, Johnson City, TN* #### Purpose of Study To determine alteration in immunological profile of preterm infants born at or before 32 weeks of gestation and hospitalized for at least one month in NICU compare to term infants with normal nursery stay. #### Methods Used It was a prospective, blinded study of two group of infants; preterm and term infants between 9-12 months of chronological age. Preterm infants were eligible for study if they were born on or before 32 weeks gestation or earlier and had hospital stay in NICU for minimum of 28 days. Inclusion criteria for term babies were birth after 37 weeks of gestation and no stay in NICU. Infants were recruited for study from Pediatric outpatient and NICU Follow up Clinic after IRB approval. Infant's blood was collected, labeled randomly and transported to research lab where it was processed and stored after centrifugation. After 20 of total 40 infants recruited; interim analysis was done as follows. Whole blood was tested with Simulttest followed by flow cytometry analysis. T cell, B cell, CD4 cell, CD8 cell, activated T cell and NK cells were calculated from 10000 events by flow cytometry. Result was analyzed by Graphpad prism for statistical significance by student T test. #### Summary of Results Total of 20 recruited infants, 9 infants were preterm and 11 were term infants. Both groups were of comparable chronological age, weight and vaccination status and devoid of any acute infection in last one month. Test results of immunological profile were shown as in Table. There is no difference between two groups in regard to number of T cell, B cell, CD4 and CD8 cell. However, there was a significant difference in activated T cell population between the two groups (*P* < 0.05). Increase in NK cells was also observed in preterm but was not statistically significant. #### Conclusions Study result shows there is a "Qualitative" difference in T cell population of preterm infants of more than 28 days of NICU stay compared to term infants even later in Infancy. View this table: [Table18](/content/57/1/301/T18) Immunological Profile of Preterm and Term Infants ### 190 "WRAPPING INTERVENTION VS. MATTRESS FOR PREVENTION OF HYPOTHERMIA STUDY" - WIMPY STUDY P.L. Simon, D. Dannaway, L. Krous, A. Wlodaver, B. Burks, C. Thi, J. Milam, M. Escobedo *OUHSC, Oklahoma City, OK* #### Purpose of Study The hypothesis for this study is: Extremely Low Gestational Age Neonates (ELGANs) resuscitated at birth on thermal warming mattresses compared to wrapping in a polyethylene sheet will experience less hypothermia on admission to the NICU. #### Methods Used For this prospective, randomized study, informed consent is obtained from the mother of any infant expected to be delivered at less than 28 weeks gestation. In the delivery room, the resuscitation team opens a sealed opaque envelope for treatment group assignment to either the wrap or the sodium acetate mattress group. Maternal temperature and delivery room temperatures are recorded prior to delivery. The baby is received from the obstetrician in a pre-warmed towel, placed on a sodium acetate thermal mattress (Infatherm) or wrapped in plastic (NeoWrap), and resuscitated as recommended in NRP. The baby is transported in a pre-warmed incubator and transferred to a radiant warmer in the NICU. Both incubator and warmer temperatures are recorded, as well as, axillary temperature on NICU admission. #### Summary of Results A total of 25 patients have been enrolled in the study. Preliminary data indicates no difference in gestational age between groups [wrap group (n = 12, GA 25.67 + 1.07 wks) and mattress group (n = 13, GA 26.23 + 1.24 wks)]. *P* value = 0.237. There are also no differences in NICU admission temperature between groups [wrap group (36.217 + 0.7) vs. mattress group (36.63 + 0.81)]. *P* value = 0.1844. Multiple linear regression confirmed that choice of particular device was not a significant predictor of admission temperature. #### Conclusions Preliminary data indicate that thermal mattresses probably do not improve the admission temperature for extremely low gestational age neonates over plastic wrap. If thermal mattresses are not superior to plastic wrap but indeed equivalent in protecting the thermal stability of ELGANs, the choice of method may then be dependent on the preference of the resuscitation personnel, economics, ease of use or other conditions of the infant. The thermal mattress may be useful in addition to the plastic wrap in some circumstances. ### 191 "COATED-PLATELETS IN NEONATES" P. Simon, G. Dale, K. Saxena *OUHSC, Oklahoma City, OK*. #### Purpose of Study Recent observations suggest that some platelets are more capable of promoting thrombin generation, and thereby affecting thrombosis or hemostasis. These unique cells contain high levels of procoagulant proteins on their surface. In a recent review article, it was suggested that this subclass of cells be referred to as coated-platelets. Several reports indicate that normal adult humans average approximately 30% of coated-platelets. Coated-platelets have the potential to serve as a prothrombotic marker and as a potential link between inflammation and thrombosis. The levels of these platelets have never been described in human neonates. The aim of the study was to determine if levels of coated-platelets in human neonates differed quantitatively from that of adult patients. #### Methods Used The study design was prospective in nature and lab personnel were blinded to patient identity. Coated-platelets levels in neonates (gest age: 32-42 weeks) were compared with previously obtained levels in healthy adults. The adult controls were typically healthy members of the faculty and staff at the Univ of OK. The neonatal population consisted mostly of asymptomatic neonates. Infants with congenital anomalies and genetic or metabolic disorders were excluded from the study population. Informed consent was obtained from the parents. Blood samples were collected and platelets were analyzed following dual agonist activation with convulxin and thrombin using flow cytometry. #### Summary of Results 12 of the 15 projected patients have been enrolled. One sample clotted prior to analysis, thus 11 samples were included in the current analysis. The data were analyzed using a two-tailed t-test. Coated-platelet levels were significantly lower in the neonates than in the adults (25.5+6.1 versus 32.2+8.6 *P* = 0.02 level). #### Conclusions The original hypothesis that infants would have a quantitatively different level of coated-platelets seems plausible. The neonatal coated-platelet levels were significantly lower than that of the adult controls in the study. Coagulation factors are generally low at birth and do not reach normal levels until around 6 months of age. Therefore, lower levels of coated-platelets might be expected in neonates. Qualitative and gestational age differences may exist between groups and should be explored in future trials. Caution should be used when interpreting these data due to the small sample size. ### 192 VEIN OF GALEN MALFORMATION PRESENTING AS PERSISTENT PULMONARY HYPERTENSION: CASE REPORT J. Surcouf1,2, L. Tran1,2, J. Ferry1,2, B. Barkemeyer1,2, D. Rivera1,2 * 1LSUHSC, New Orleans, LA and 2Children's Hospital, New Orleans, LA*. #### Case Report Vein of Galen malformation is a congenital arterio-venous fistula with associated cardiovascular and neurologic complications that may present in the newborn period. A term male neonate born via repeat cesarean section experienced respiratory distress and hypoglycemia at 3 hours of life. An evaluation for infection was performed and the baby was placed on high flow nasal cannula and antibiotics. A heart murmur and hyperdynamic precordium were noted on day 2 of life. Echocardiogram revealed mild pulmonary hypertension with normal cardiac structure. On the 4th day of life the infant required intubation for worsening respiratory distress. Chest radiograph revealed an enlarged cardiac silhouette. Repeat echocardiogram was consistent with worsening pulmonary hypertension. The infant was noted to have a bruit over the anterior fontanelle. A head ultrasound revealed a vascular abnormality and a CT scan confirmed a Vein of Galen malformation. The infant underwent four endovascular coil procedures to reduce the hemodynamic disturbances created by significant shunting through the malformation. Severe pulmonary hypertension, high output heart failure, systemic steal phenomena, portal hypertension and liver failure were managed medically with pulmonary vasodilators, low dose inotropes, diuretics and afterload reduction. The infant's clinical status significantly improved after the 4th coil procedure but he subsequently developed seizures as a result of a post-embolization hemorrhage. A ventricular access device was placed and multiple anticonvulsants were required for seizure control. A gastrostomy and fundoplication were ultimately required for feedings. The infant was discharged home on day of life 165 on multiple medications and home oxygen. Vein of Galen malformation is an unusual etiology for pulmonary hypertension of the newborn but should be suspected in the presence of cardiomegaly and in the absence of other obvious causes. Severe complications as a result of the known hemodynamic changes (Patel, 2007) can be managed with both pulmonary and systemic vasodilators. This difficult case underscores the importance of high suspicion for diagnosis and the need for multi-sub-specialist management to achieve the best possible outcome. ### 193 MULTIPLE CONGENITAL ANOMALIES IN AN INFANT OF AN OBESE DIABETIC MOTHER: CASE REPORT L. Tran1,2, J. Surcouf1,2, J. Ferry1,2, S. Olister1,2 * 1LSUHSC, New Orleans, LA and 2Children's Hospital, New Orleans, LA*. #### Case Report The incidence of congenital malformations is increased four to eight-fold in infants of insulin-dependent, diabetic mothers. CNS, cardiovascular, musculoskeletal, gastrointestinal, and genitourinary anomalies occur in these infants and account for 30-50% of their perinatal mortality. The risk of congenital anomalies is increased in the offspring of obese women with diabetes (Allen, 2007). Martinez-Frias (2005) reports that the greater the body mass index in mothers with gestational diabetes, the higher the risk for congenital malformations in their offspring. We describe a case of diabetic embryopathy in an obese insulin-dependent, diabetic mother. CASE REPORT: A female child was delivered at 34 1/7 weeks to a 19 year old G1P0 mother via Cesarean section secondary to non-reassuring fetal heart tones. Pregnancy was complicated by insulin-dependent diabetes, morbid obesity, polyhydramnios and a prenatal diagnosis of hypoplastic left heart. At birth, APGAR scores were 5 and 8 at one and five minutes. Birth weight was 1967 g. Echocardiogram confirmed the diagnosis of hypoplastic left heart, including mitral and aortic valve atresia, large patent ductus arteriosus, and moderate atrial septal defect. Other abnormalities included an absent right kidney and multiple choroid plexus cysts. Abdominal radiograph revealed the classic "double bubble" sign of duodenal atresia. An exploratory laparotomy performed on day of life three confirmed duodenal atresia as well as a small distal intestine and malrotation of the colon. These anomalies are most likely due to maternal diabetic embryopathy. Genetic analysis by microarray is pending to confirm the nonchromosomal nature of these abnormalities. Teratogenesis in this infant is likely due to the multifactorial etiology of impaired glycemic control and associated derangements in maternal metabolism which disturb embryonic development. Moore (2000) suggests that obesity and diabetes mellitus may act synergistically in the pathogenesis of congenital anomalies. Planned pregnancy and preconception counseling are necessary in women with diabetes to optimize general health, glycemic control and pre-pregnancy weight to reduce the risk of congenital anomalies. ### 194 SPECTRAL ANALYSIS OF SUCK AND SWALLOW RHYTHMS DURING INFANT FEEDING P. Vijaygopal1, A. Patwardhan1, E. Reynolds2 * 1University of Kentucky, Lexington, KY and 2University of Kentucky, Lexington, KY* #### Purpose of Study Previous authors have used labor-intensive methods to describe the stability and progression of suck and swallow rhythms in infants. The purpose of this study is to simplfy the analysis of feeding rhythms and investigate the utility of this type of analysis in describing developmental and maturational changes in these rhythms over time and with disease states. #### Methods Used Study participants were low-risk preterm infants with minimal respiratory support, no IVH, no congenital anomalies and no concurrent infection. Physiologic data were collected by instrumenting the patients with: 2-types of acoustic detectors for cervical auscultation, a naso-pharyngeal catheter to record swallow pressure, a catheter placed through the nipple of a bottle to measure suckle pressure, a thermistor at the nares to measure airflow, a chest band to measure thoracic motion and a pulse oximeter. Feeding data was displayed as an 8-channel linear graph using the Windaq Acquisition System (Dataq Inst, Akron OH). Periods between feeding runs were ignored so only times when the baby was actively feeding were considered. 8 feeding studies were analyzed. Specral data included bandwidth (BW), 50%-power (50-p) and peak frequency (PF). #### Summary of Results Results are shown on the following table. Linear regression was used to determine relationships between day of life (DOL) and post-menstrual age (PMA) with the spectral data. BW for suckle compared to DOL and PMA suggest a possible correlation, but there is insufficient data at this time to reach statistical significance. View this table: [Table19](/content/57/1/301/T19) Spectral Analysis of Suck and Swallow #### Conclusions Spectral analysis of feeding rhythms offers a new way to measure the stability of these rhythms and possibly a new tool for the investigation of maturation and development of infant feeding. Changes in spectral data over time and in diseased populations warrants further investigation. ### 195 CLINICAL POTENTIAL OF FETAL NEOPLASMS L.D. Young-Gaylor, A.C. Mullins, D.R. Shanklin *University of Tennessee, Memphis, Memphis, TN*. #### Purpose of Study Relative success in recent years in reducing the morbidity and mortality in preterm infants has enhanced the clinical significance of malformations and neoplasms in neonatal care. The comparative and specific roles of cerebral, cardiovascular, and urogenital anomalies are well known [Sotelo-Avila and Shanklin, *Arch.Pathol.* 84:373-279, 1967]. By contrast, developmental tumors are less common and rather underappreciated. #### Methods Used We found 34 neoplasms in 1300 autopsies over a 25 year period (1983-2008), a prevalence of 2.62%, in the University of Tennessee perinatal database. #### Summary of Results These were: cystic hygroma and other lymphangiomatoses (7); adrenal neuroblastoma-in-situ (6); massive cerebral tumors (5), including one neurogenic teratoma; leukemia (3), two of which manifested in Down syndrome; giant sacrococcygeal teratoma (2); systemic fibrohistiocytosis (2); nephroblastoma-in-situ (2); one each embryonal lymphoma, embryonal seminoma, giant placental hemangioma, and systemic neurofibromatosis, and three miscellaneous types. Twenty one were in newborns and 13 in stillborns, one of the latter after intracranial decompression for the neurogenic teratoma. Progression of adrenal neuroblastoma-in-situ and renal nephroblastoma-in-situ to their definitive form is often assumed [Shanklin and Sotelo-Avila, *Biol.Neonat.* 14:286-316, 1969] but intermediate examples are difficult to assess. The large proportion of tumors of the lymphatic and neurologic systems is noteworthy. A major problem for case management is the strong tendency of these tumors to grow at rates similar to growth of the normal fetus in the third trimester; many of our cases presented as bulky tumors and the intracranial ones often occupied one or both cerebral hemispheres. #### Conclusions Improvements in obstetrical and neonatal care over these 25 years suggest some of those stillborn in our database might now be delivered alive. Such tumors are significant challenges to neonatal and infant care. Some aspects of their clinical presentations may contribute to differential diagnosis in pediatric emergency care, including but not limited to seizures, intestinal and urinary obstruction, anemia, and thrombocytopenia. ## **Pulmonary and Critical Care Medicine Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 196 SOLUBLE CD40 LIGAND EFFECTS ON PULMONARY MICROVASCULAR ENDOTHELIAL CELL PROLIFERATION AND BARRIER INTEGRITY J. Baker, T. Moore *University of South Alabama College of Medicine, Mobile, AL*. #### Purpose of Study Previous studies in pulmonary microvascular endothelial cells (PMVEC) have indicated soluble CD40 ligand (sCD40L), a trimeric protein belonging to the TNF family, plays a role in endothelial function. In acute lung injury (ALI), sCD40L and its receptor, CD40, are implicated in the mechanism of non-cardiogenic pulmonary edema development. However, it is unknown mechanistically how sCD40L-CD40 signaling affects PMVEC barrier function. We hypothesized that sCD40L directly regulates barrier integrity. Because CD40 receptor activation is also associated with systemic endothelial cell proliferation, we tested whether proliferation responses and barrier integrity were related. #### Methods Used Growth curves and transendothelial resistance (TER) measurements were carried out using rat PMVEC. Confluent rat PMVEC passaged for growth curve analysis were either pre-treated for one hour (before barrier disruption with trypsin) or post-treated (after barrier disruption with trypsin) with increasing sCD40L concentrations. Growth curves were compared with control curves and doubling times calculated. TER was measured using an ECIS apparatus (Applied Biophysics). #### Summary of Results Pre- and post-treatment with sCD40L (1 μg/mL) increased the amount of adhered cells 24 hours after re-seeding compared to the untreated PMVEC, whereas pre-treatment of PMVEC with sCD40L also decreased doubling time. These data suggested that both early and sustained proliferation rates could be increased by sCD40L, and revealed that the timing of sCD40L exposure was important in the proliferation response. TER measurements for both pre- and post-treatment showed an increased monolayer resistance at 60 hours compared to untreated PMVEC, whereas pre-treatment with sCD40L produced increased TER values as early as 48 hours post-seeding. These findings also suggested sCD40L exposure prior to barrier disruption was necessary for accelerating and enhancing resultant reformed barrier integrity. #### Conclusions Together, our data indicate sCD40L produces pro-proliferative responses during barrier disruption and repair with resultant decreased barrier reformation times and strengthened integrity. Pharmacologic agents affecting sCD40L-CD40 signaling during ALI might help reduce ALI-associated morbidity and mortality by facilitating microvascular repair. ### 197 ROSIGLITAZONE ATTENUATES CHRONIC HYPOXIA-INDUCED PULMONARY HYPERTENSION AND LOWERS LUNG ENDOTHELIN-1 IN MICE A. Gluzman1, D. Kleinhenz2, C. Hart2,1 * 1Emory University, Atlanta, GA and 2Atlanta VAMC, Atlanta, GA*. #### Purpose of Study The peroxisome proliferator-activated receptor gamma (PPARγ) ligand, rosiglitazone, ameliorates indices of pulmonary hypertension (PH) induced by chronic hypoxia (CH) in mice. To explore the mechanisms by which rosiglitazone modulates PH, we examined endothelin-1 (ET-1), which stimulates vasoconstriction and cell proliferation to contribute to the pathogenesis of PH. We hypothesized that rosiglitazone attenuated pulmonary hypertension by reducing hypoxia-induced stimulation of the endothelin pathway. #### Methods Used Male C57BL/6 mice were exposed to CH (FiO2 10%) or room air for 3 weeks. During the last 10 days, mice were treated with either rosiglitazone (10 mg/kg/day) or with an equal volume of vehicle (100 μL 0.5% methylcellulose) by gavage daily. After sacrifice, ET-1 levels were measured in whole lung homogenates with an ELISA assay. Levels of endothelin A and B receptor (ETR-A and ETR-B) mRNA were quantified by real-time PCR from whole lung homogenates. Data were analyzed by one-way ANOVA. #### Summary of Results Compared to exposure to control conditions, CH increased ET-1 levels in whole lung homogenates from 65 ± 4 pg/mL in controls to 368 ± 56 pg/mL (mean ± SEM, n = 6, *P* < 0.001). Treatment with rosiglitazone had no effect on ET-1 levels in control mice but lowered ET-1 levels to 234 ± 25 pg/mL (*P* < 0.05). Although, treatment did not alter mRNA levels of ETR-A, treatment with rosiglitazone increased ETR-B mRNA levels in control and CH-exposed mice. #### Conclusions The PPARγ ligand, rosiglitazone, attenuates CH-induced pulmonary hypertension in mice, in part, by decreasing ET-1 levels. Although the exact mechanism for these effects of rosiglitazone on ET-1 signaling remains to be determined, increased ETR-B, which clears ET-1 from the circulation and mediates endothelium-mediated vasodilation may contribute to previously observed rosiglitazone-mediated reductions in pulmonary hypertension. ### 198 VIRAL STUDIES ON BRONCHOALVEOLAR LAVAGE FLUID D. Guerra, R. Alalawi, R. Raj, K. Nugent *Texas Tech University, Lubbock, TX*. #### Purpose of Study Viral studies on bronchoalveolar lavage fluid may provide definitive diagnostic results (influenza A isolates) or confusing clinical data (Herpes isolates). The utility of these studies remains uncertain, and we wanted to review our data to determine patient characteristics and outcomes #### Methods Used We reviewed all lavage results collected between December 2006 and August 2008 and identified patients with Herpes simplex (HSV) isolates or cytomegalovirus (CMV) isolates. We recorded patient characteristics, radiographic results, and outcomes. #### Summary of Results 154 lavage studies were done by the pulmonary service during this period. Seven patients had HSV isolates. The age range was 44-69; four patients were men. Seven patients had cough, three had dyspnea, and three had fever. Six had chronic pulmonary disease, cardiac disease, and/or malignancy. One plain X-ray was clear; six CTs revealed ground glass opacities. DFA was positive in six patients and cultures were positive in four. Three patients received acyclovir. One died and six were stable or improved. Six patients had CMV isolates. The age range was 37 to 66; five were men. Two patients had cough, four had dyspnea, and four had fever. Four patients had AIDS (meanCD4 ct-), one a lymphoma, and one a renal transplant. X-rays/ CTs were normal in two and revealed ground glass opacities in four. One patient received anti CMV therapy and improved. The others improved with treatment of other medical diagnoses #### Conclusions All patients with HSV isolates had symptoms and six had abnormal radiographic studies. However, the pathogenetic significance of this infection is unclear, and there was no obvious benefit with antiviral therapy. Our patients with CMV had significant immunosuppression, but the isolation of this virus may not have represented an infection as most patients improved without specific therapy ### 199 SLEEP AND IMMUNITY: RELATIONSHIP OF LYMPHOCYTES AND APNEA HYPOPNEA INDEX D. Kadaria, L.C. Murillo, J.C. Yataco, J.F. Avecillas, A.X. Freire *UT Health Science Center, Memphis, TN*. #### Purpose of Study Sleep loss is believed to adversely affect diverse immune functions (lymphopenia). As opposed to the well defined effects on immunity of acute, laboratory induced, sleep deprivation; the impact of chronic, interrupted, poor quality sleep-as seen in obstructive sleep apnea (OSA)-has not been thoroughly evaluated. We aim to explore the relationship between leukocyte/lymphocyte counts and Apnea Hypopnea Index (AHI) in patients diagnosed with OSA (stratified by severity). #### Methods Used We conducted an IRB approved retrospective review (October 2005 - July 2006) of 122 patients diagnosed with obstructive sleep apnea using a full-night diagnostic polysomnogram (PSNG). Data collected were demographics, co-morbidities, total neutrophil, & lymphocyte count, Body Mass Index (BMI), AHI and Epworth sleepiness scales (ESS). For the AHI variable, three strata were constructed: mild (5-14), moderate (15-29), and severe (>30). We described data with frequency terms, continuous data by mean + standard deviation (+ SD), and categorical data by counts & percentages. Student t test or one-way ANOVA were used when appropriate to compare continuous variables; Chi-Squared test (χ2) for categorical variables. Data were later fitted in a linear regression model on which lymphocyte counts were the dependent variable, against age, BMI, AHI. All tests are two-sided and a *P* < 0.05 was considered as statistically significant. We used Statview Version 5.01 (SAS institute Inc. Cary, NC) for the statistical analysis. #### Summary of Results Our study showed a linear association among AHI (dependent) & BMI (predictive variable) *P* = 0.0017 but did not show a significant association between lymphocyte count with: either BMI (*P* = 0.33) or AHI (*P* = 0.90). A negative association between Lymphocyte and age (*P* = 0.02) was found that persisted even after multiple linear regression adjustment for BMI & AHI. An interaction product was also explored (age*AHI) but such carrier was not associated statistically with the lymphocyte count (*P* = 0.87). #### Conclusions We found that chronic, interrupted, poor quality sleep-as seen in OSA -was not associated with lymphocyte counts and AHI severity did not influenced it either. ### 200 CUFF-LEAK TEST: A SYSTEMATIC REVIEW AND META-ANALYSIS OF CASE SERIES Z. Mulkey, D. Guerra, C. Jumper, K. Nugent *Texas Tech University Health Sciences Center, Lubbock, TX*. #### Purpose of Study Cuff leak tests provide clinicians with information about upper airway narrowing and may help predict weaning success. However, most clinical trials reporting this measurement are small, and the utility of this test remains uncertain. In particular, the threshold value demonstrating upper airway narrowing is uncertain. #### Methods Used We identified all clinical studies using cuff leak tests in the PubMed data base using multiple search terms, including cuff leak, laryngeal edema, extubation and stridor. #### Summary of Results We reviewed ten studies which included 1700 patients. Eight studies provided quantitative information, and two studies provided qualitative information about cuff leaks. Study endpoints were either stridor or reintubation or both. 7.2 percent of the patients had stridor post extubation. The weighted mean cuff-leak in patients with stridor was 103 ± 108 ml. The weighted mean cuff-leak in patients without stridor was 376 ± 181 ml (*P* < 0.01). Six studies used receiver operating curves or provided other estimates of threshold values for separating the study population into two groups with high or low leaks. The mean value from this analysis was 115 ml. Sixty four patients (3.6%) required reintubation. The presence of stridor accurately identified patients who would require reintubation. This physical finding had a sensitivity of 0.76(95% CI 0.62-0.85) and a specificity of 0.97((95% CI 0.96-0.98). There were important differences among these studies in the method used to measure cuff-leak. #### Conclusions Patients with post-extubation stridor have smaller cuff-leak volumes than patients who do not have stridor and are more likely to require reintubation. Cuff-leak measurements have the potential to improve decision making with extubation protocols, but this field needs more prospective studies with standardized methods for cuff leak measurement. ### 201 MANAGEMENT OF BRONCHIOLITIS IN A PEDIATRIC EMERGENCY DEPARTMENT: A COMPARISON TO NATIONAL GUIDELINES C. Pruitt, K. Monroe, W. King *University of Alabama at Birmingham, Birmingham, AL*. #### Purpose of Study To describe physician practices in the management of bronchiolitis as compared to the American Academy of Pediatrics Clinical Practice Guideline, and to determine how much divergence may be accounted for by a history of asthma or prior wheezing episodes. #### Methods Used We conducted a retrospective chart review of all cases of bronchiolitis presenting to our institution from October 2007 through March 2008. All patients were less than 24 months old. Charts were selected by the presence of the International Classification of Diseases, Ninth Revision code for bronchiolitis. In addition, charts including codes for "wheezing", "respiratory distress", or "asthma" were reviewed and included if the patients met clinical criteria for the diagnosis of bronchiolitis. Children with a history of inhaled corticosteroid use were excluded. #### Summary of Results Preliminary chart review yielded 152 cases that met inclusion criteria. 20 patients (13.2%) carried a diagnosis of asthma, and 53 patients (34.9%) had a history of wheezing without a diagnosis of asthma. A chest roentgenogram was obtained for 65 patients (42.5%); this practice did not vary based on history of asthma or wheezing. 103 patients (67.3%) received bronchodilators; those with a history of asthma and a history of wheezing alone were both significantly more likely to receive bronchodilators (95.0% and 96.9%, respectively) than patients with no such history (52.1%) (*P* < 0.001). 38 children received corticosteroids (24.8%), consisting of 80% of asthmatics, 42.4% of those with a history of wheezing, and 7.3% of patients with no such history (*P* < 0.05 for all proportion comparisons). Antibiotics were prescribed for 20 patients (13.1%), hydration status was documented for 147 children (97.4%), and the presence or absence of tobacco smoke exposure was recorded for 56 patients (36.6%). #### Conclusions Physician practice in the care of children with bronchiolitis differs from national guidelines in many respects. Many of our data are similar to those from similar studies prior to the publication of these guidelines. However, our stratified analyses suggest that the relatively frequent use of bronchodilators and corticosteroids in these patients may be attributable to their respiratory history. ### 202 CAN TONOMETRIC INTRAOCULAR PRESSURE MEASUREMENT IN CHILDREN WITH HEAD TRAUMA REPLACE THE NEED FOR INTRACRANIAL PRESSURE MONITORING? T. Spentzas1, J. Henricksen1, A. Patters3, E. Chaum2 * 1University of Tennessee, Memphis, TN; 2University of Tennessee, Memphis, TN and 3University of Tennessee, Memphis, TN* #### Purpose of Study Children with severe traumatic brain injuries (TBI) commonly develop increased intracranial pressure (ICP) requiring the surgical placement of a ventricular bolt with an external transducer to accurately measure ICP during the acute post-traumatic period. We hypothesized that increased ICP in these patients may cause engorgement of the orbital compartments via dilation of the episcleral veins and manifest as an increase in the measured intraocular pressure (IOP). The goal of this study was to correlate tonometric measurement of the IOP with ICP in patients with ventricular transducers to determine whether IOP can be used as a surrogate measure of increased ICP in children with TBI. #### Methods Used We performed an IRB-approved, prospective study on 27 children admitted to the LeBonheur Children's Medical Center PICU with TBI and altered mental status requiring placement of an ICP transducer. A total of 183 IOP measurements were made in the children following placement of the transducer. In addition to ICP and IOP, we also documented central venous pressure (CVP) and the concordance of the site of the injury. #### Summary of Results Krippendorff's alpha reliability for IOP as a surrogate measurement for ICP was a = 0.746 (L=0.671, U=0.809) and improved with concordance of the injury site to the eye on that side to a = 0.813 (L = 0.748 U = 0.867). The difference between simultaneous IOP and ICP measurements had a standard deviation of 4.7 and improved to 4.0 with concordance, i.e., 96 % of the ICP measurements were within ± 8 cm H2O of the measured IOP (Bland Altman organ calibration). Using 20 cm H2O as a normal ICP cutoff, the IOP had a specificity = 0.7 (L = 0.58, U = 0.81) and sensitivity = 0.97 (L = 0.93, U = 1.00), and with concordance improved to 0.78 and 0.96, respectively. We did not identify any correlation between the CVP measurement and the IOP. #### Conclusions Tonometric IOP can be a useful screening tool as a surrogate measure of ICP in children with TBI, but appears to lack the accuracy necessary for close, accurate management of the ICP in the acute post-traumatic period, based upon our current data ### 203 ASSESSING THE EFFECTIVENESS OF HIGH-FLOW NASAL CANNULA IN CHILDREN WITH RESPIRATORY DISTRESS VIA THE COMFORT AND RESPIRATORY DISTRESS CLINICAL SCALES. IS GENERATION OF POSITIVE NASOPHARYNGEAL PRESSURE THE MECHANISM OF ACTION? T. Spentzas1, M. Minarik1, A. Patters3, B. Vinson2, G. Stidham1 * 1University of Tennessee, Memphis, TN; 2University of Tennessee, Memphis, TN and 3University of Tennessee, Memphis, TN* #### Purpose of Study High-flow nasal cannula (HFNC) therapy is a treatment for respiratory distress in neonates and children. With the present study, we assessed its effectiveness, comfort and possible mechanism of action. #### Methods Used We reviewed 46 records of patients treated with high-flow nasal cannula and estimated the modified COMFORT score (7 to 35 units), the respiratory clinical scale (0 to 12 units) and the oxygen saturation level. Data were collected at time 0 (before the use of high-flow), time 2 (60 to 90 min post-application) and at time 3 (8 to 12 hours post-application). Furthermore, we measured the nasopharyngeal pressure while on continuous positive air pressure (CPAP) as well as the differences in "lung expansion" demonstrated by the pre- and post-study chest x-ray. #### Summary of Results There were significant improvements in the modified COMFORT score [F (1, 45) = 40.03, *P* < 0.05], respiratory clinical scale F [(1.69, 76.15) = 121.19, *P* < 0.05] and oxygen saturation [F (2, 90) = 101.54, *P* < 0.05]. Application of HFNC therapy created a significant average positive expiratory pressure of 4.0 ± 1.99 cm H2O. The x-rays after initiation of HFNC showed either improved aeration of the lungs or no changes in 40 of 46 patients. Mechanical ventilation was needed in 5/46 patients. #### Conclusions Our study indicates that high-flow nasal cannula improves the respiratory scale score, the oxygen saturation, and the patient's COMFORT scale. Finally, the mechanism of its action is application of mild positive airway pressure and lung volume recruitment. ### 204 AMIODARONE INDUCED LOCULATED PLEURAL EFFUSION: CASE REPORT AND REVIEW OF LITERATURE P.V. Uong, K. Nugent, R. Alalawi, R. Raj *Texas Tech University Health Sciences Center Lubbock, Lubbock, TX* #### Case Report INTRODUCTION: We describe the first reported case of a drug induced loculated pleural effusion secondary to amiodarone and review the literature on amiodarone induced pleural effusions. CASE REPORT: A 70 year old female who had been on amiodarone for 2 years presented with pleuritic chest pain and dyspnea 4 weeks after her amiodarone dose was increased from 200 mg to 600 mg daily. No clinical or echocardiographic evidence of congestive heart failure was present. CT chest showed bilateral free flowing effusions without any infiltrates. Thoracentesis revealed a neutrophilic exudative effusion. Amiodarone was continued and 4 days later she developed worsening hypoxia, patchy infiltrates and loculations in the left pleural effusion. Transbronchial biopsy showed foamy macrophages and interstitial pneumonitis consistent with amiodarone toxicity. A thorough work up was negative for other causes of the effusion including but not limited to infections, congestive heart failure, pulmonary emboli and connective tissue diseases. A diagnosis of amiodarone induced pleural effusion was made. The effusion resolved completely after stopping amiodarone and a short course of corticosteroids. Review of literature showed no reported cases of loculated pleural effusions secondary to amiodarone or any other drug. Free flowing pleural effusions secondary to amiodarone are rare but have been reported. Amiodarone induced pleural effusions are exudates, often asymmetric and sometimes unilateral, may have foamy macrophages in the pleural fluid, are usually but not always associated with amiodarone pneumonitis and can occur even at low doses of amiodarone. Treatment included corticosteroids and discontinuing amiodarone. CONCLUSIONS: Amiodarone induced pleural effusions should be considered in the differential diagnosis in patients on amiodarone with exudative effusions for which there is no other explanation. Presence of loculations in the effusion does not exclude drugs as the cause of the effusion. Recognition of these rare presentations will result in timely diagnosis and treatment of patients these pleural effusions. ### 205 ROSIGLITAZONE ATTENUTATES HIF 1α UP-REGULATION IN HYPOXIA EXPOSED HUMAN PULMONARY ARTERY SMOOTH MUSCLE CELLS H.M. Ward1,2, A. Gluzman1,2, J. Bland2, D. Kleinhenz1,2, C.M. Hart1,2 * 1Emory University, Atlanta, GA and 2Atlanta VA Medical Center, Atlanta, GA*. #### Purpose of Study Hypoxia inducible factor (HIF 1α) mediates alterations in gene expression in response to hypoxia. Many HIF 1α responsive genes promote cell proliferation. Hypoxia constitutes a common stimulus for the development of pulmonary hypertension which is characterized by pulmonary vascular remodeling and vascular cell proliferation. We have shown that the PPARγ ligand, rosiglitazone, attenuates chronic hypoxia-induced pulmonary hypertension in mice. We hypothesized that rosiglitazone mediates this effect by suppressing HIF 1α gene expression and protein synthesis. #### Methods Used To test this hypothesis, cultured human pulmonary artery smooth muscle cells (HPASMC) were exposed to normoxic (21% O2, 5% CO2) or hypoxic (10% O2, 5% CO2) conditions for 72 h. Cells were treated with rosiglitazone (10 μM) or vehicle (0.5% methyl cellulose) for the last 24 h of exposure. HPASMC were then harvested in normoxic or hypoxic environments, and mRNA and proteins were collected. #### Summary of Results As expected HIF 1α protein levels were significantly up-regulated by hypoxia, and rosiglitazone attenuated hypoxia-induced increases in HIF 1α protein. mRNA levels for HIF 1α were not different among all treatment groups. #### Conclusions We postulate that rosiglitazone-induced suppression of HIF 1α protein expression in response to hypoxia decreases proliferative signaling pathways and gene expression involved in the pathogenesis of vascular remodeling and pulmonary hypertension. This novel observation suggests that PPARγ activation by rosiglitazone can modulate the fundamental mechanisms involved in pulmonary vascular responses to hypoxia that contribute to pulmonary hypertension. ### 206 ENDOBRONCHIAL EXTENSION OF ASPERGILLOMA S.J. Zaidi, A. Elgamal, A.X. Freire *University of Tennessee, Health Science Center, Memphis, Memphis, TN*. #### Case Report A 63 year old African American male with history of uncontrolled rheumatoid arthritis was sent to our pulmonary clinic by rheumatology for evaluation of a right upper lobe (RUL) abnormality. Screening chest x-ray was ordered before starting anti-cytokine therapy, which showed RUL cavitary lesion. Patient denied any weight loss, dyspnea, cough, fever, chest pain, or hemoptysis. He admitted having pulmonary tuberculosis 15 years ago treated for 9 months. Chest computed tomography confirmed the findings with a suspicion of a "fungus ball" within the cavity. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F11.medium.gif) [Figure.](/content/57/1/301/F11) Figure.   Bronchoscopy was performed which showed two endobronchial lesions at the origin of RUL apical and posterior segments. Bronchoalveolar lavage and multiple biopsies were taken which confirmed the diagnosis of Aspergillus flavus. Endobronchial extension of a pulmonary aspergilloma is a rare and unusual finding of a relatively common fungal infection. In our patient the absence of any pulmonary symptoms makes it even more unique. ## **Renal, Electrolyte and Hypertension Joint Poster Session** 5:00 PM Thursday, February 12, 2009 ### 207 MULTIPLE MYELOMA ASSOCIATED HYPERCALCEMIA: AN UNUSUAL CAUSE OF MILK ALKALI SYNDROME H.M. Alshayeb1, V. Patel2, T. Mangold2, B.M. Wall2,1 * 1UT-Memphis, Memphis, TN and 2VAMC, Memphis, TN. Case Report*. #### Case Report The classical milk alkali syndrome (MAS) consists of the triad of hypercalcemia (hyperCa + 2), metabolic alkalosis (M. alkalosis) and reduced GFR, typically associated with ingestion of large amounts of exogenous Ca + 2 and alkali. This report describes an unusual case of MAS in which the endogenous release of Ca + 2 and carbonate from diffuse osteolytic lesions of multiple myeloma (MM) resulted in the hyperca + 2 and M.alkalosis. The associated ↓GFR secondary to MM-nephropathy and hyperca + 2 completed the triad of MAS in the absence of exogenous intake of Ca + 2 and alkali. A 51 Y/O male presented with generalized fatigue, ↓ appetite, weight loss, constipation, and chest wall pain of one month duration. Physical examination was unremarkable. Laboratory evaluation showed a HCT of 34%, and platelet count of 307 × 109/L. Serum electrolytes in mEq/l were: Na + 142, K + 4.3, CL- 96, HCO3 - 37, Ca + 2 18 mg/dl, PO4 -3 6 mg/dl, BUN 38 mg/dl and Cr 2.6 mg/dl. Urine Cl- 48 mEq/l. Other labs included normal TSH, suppressed PTH 10 pg/ml (10 - 65 pg/ml), Low PTH-rP < 0.3 pg/ml (0.0-1.5 pg/ml), plasma aldosterone 7.6 ng/dl (1-16 ng/dl), low plasma renin activity 0.42 ng/ml/hr, and random morning cortisol of 20 μG/dl (4-24 μg/dl). Urinalysis showed trace protein, pH of 5.0, and specific gravity of 1.007. Skeletal survey showed chest wall mass and widespread lytic bone lesions. Total protein was 8.3 g/dl and albumin 4.1 g/dl. Serum and urine immunelectrophoresis(IFE) revealed IgG λ and free λ light chain. Histopathology of the chest wall mass and bone marrow biopsy confirmed the diagnosis of MM. Other causes of M.alkalosis including vomiting, diuretics, alkali ingestion, blood transfusion and hypokalemia were excluded. Hyperca + 2 and M.alkalosis were only partially corrected after IV hydration, furosemide, calcitonin and steroids. Treatment with bisphosphonstes corrected the hyperCa + 2(Ca + 2 10 mg/dl) and metabolic alkalosis (HCO3- 27 mmol/l). #### Conclusion The extensive release of Ca + 2 and carbonate from lytic bone lesions by activated osteoclasts with minimal osteoblastic activity in this patient with MM likley explains the associated hyperCa + 2 and M.alkalosis. The ↓ GFR further impaired HCO3- excretion resulting in MAS in the absence of exogenous Ca + 2 or alkali intake. ### 208 COMPARISON OF CLINICAL OUTCOMES IN AN AMERICAN AND EUROPEAN DIALYSIS UNIT B. Bean1, M. Zsom2, S. Lam1, D. Schmidt1, L. Zsom1, C. Wells1 * 1Univ of MS Medical Center, Jackson, MS and 2Diaverum Dialysis Center, Baja, Hungary*. #### Purpose of Study To compare currently used measures of dialysis outcomes among varying dialysis units #### Methods Used chart review, review of clinical outcome measures (e.g., albumin, crp, Kt/V) #### Summary of Results Despite wide variations in demographic characteristics and comorbid conditions between patient populations in the dialysis units, favorable outcomes in regard to measures of outcomes could be achieved. Of note, there was statistically significant difference in dialysis times #### Conclusions More studies are needed to assess if longer dialysis times may offset traditionally considered effectors of dialysis such as age, vintage, and comorbid conditions ### 209 VARIABILITY OF INDIVIDUAL URINE PROTEINS ASSOCIATED WITH BLOOD PRESSURE AND MEDICATIONS DIFFERENCES IN DIABETIC NEPHROPATHY M. Mataria1,2, A. Bland1, M. Janech1,2, E. Lewis1,2, J. Arthur1,2 * 1Medical University of South Carolina, Charleston, SC and 2Ralph H Johnson VA Medical Center, Charleston, SC* #### Purpose of Study Identifying the effect of blood pressure control and blood pressure medications on urinary proteins abundance among diabetic patients #### Methods Used Urine samples from 18 patients with diabetic nephropathy were collected and proteins were separated by 2-D gel electrophoresis. We compared the proteins to determine if differences in medication or blood pressure at the time of collection were associated with changes in the abundance of individual proteins. Comparisons of protein abundances were made between classes of antihypertensive medications and groups of high blood pressures. #### Summary of Results Protein spots were statistically different between the Systolic (11 spots) and diastolic pressure (12 spots) groups, ACE/ARB groups (8 spots), dihydropyridine CCB groups (2 spots) and non dihydropyridine CCB groups (8 spots). We further analyzed these groups to see if the protein abundance for the statistically different proteins segregated based on the medications or based on the blood pressure values. We did not find a major association. The greatest degree of segregation occurred for spot 2501 between with and without ACE/ARB (Panel A). There was a large amount of overlap between groups. Protein abundance did not segregate continuously based on medications either. The best correlation was for spot number 3002 shown in panel B (R2 = 0.43). #### Conclusions These data confirm that factors beyond those associated with renal prognosis can change the expression of specific proteins in the urine but that there is not a strong association with any individual proteins when a group of patients is studied. ### 210 PROTEINURIA THE "TIP OF THE ICEBERG": A CRITICAL FINDING IN HIV ASSOCIATED NEPHROPATHY C.L. Moll1, L. Sicinschi2 * 1Louisiana State University Health Science Center, New Orleans, LA and 2Louisiana State University Health Science Center, New Orelans, LA*. #### Case Report HIV Associated Nephropathy (HIVAN) is the third leading cause of end-stage-renal disease (ESRD) among African Americans age twenty to sixty years of age. It is an aggressive renal disease commonly characterized by proteinuria, azotemia, normal-to-large kidneys, normal blood pressure, and focal segmental glomerulosclerosis. We report the case of a 53-year-old African American woman with newly diagnosed hypertension and an unremarkable social history who presented to the emergency department complaining of dysphagia, odynophagia, and weight loss for 3 weeks. She was seen by her primary care physician 1 week prior to admission and was found to have acute renal failure. At presentation to the ED, she had an elevated blood pressure and a benign physical exam. Labs were significant for anemia, elevations in BUN and creatinine, and low albumin. Nephrotic range proteinuria was demonstrated by urinalysis. Renal ultrasound showed bilateral increased echogenicity consistent with medical renal disease. IV fluids were started and patient samples were sent to differentiate possible causes of acute renal failure including HIV, Syphilis, Lupus, and Rheumatoid Arthritis. A diagnostic renal biopsy was done and histological findings were consistent with focal segmental glomerulosclerosis, collapsing type. The patient's renal function worsened and she required hemodialysis during the rest of her hospital course. She was diagnosed, by tissue biopsy, with candida esophagitis and successfully treated with fluconazole. The patient had a seropositive HIV test which led to the diagnosis of HIVAN. HIVAN accounts for 60% of HIV nephropathy and has mortality close to 50%. HIV replicates within renal cells, creating a reservoir for the virus even when viremia is undetectable. The introduction of antiretroviral therapy (HAART) has been associated with a decline in the incidence of HIVAN. Aggressive initiation of HAART and ACE inhibitors for patients with advanced HIV disease is the current standard of therapy to delay disease progression. Physicians should consider HIVAN in patients who are seropositive for HIV and have proteinuria. ### 211 PLASMA HOMOCYSTEINE IS ADERSELY ASSOCIATED WITH GLOMERULAR FILTRATION RATE IN BLACK AND WHITE YOUNG ADULTS: THE BOGALUSA HEART STUDY L. Ruan1,2, W. Chen1, S.R. Srinivasan1, J. Xu1, A. Toprak1, G.S. Berenson1 * 1Department of Epidemiology, New Orleans, LA and 2The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China*. #### Purpose of Study That plasma homocysteine is elevated markedly in renal dysfunction is well recognized. But whether the increased homocysteine is an independent risk factor for impaired renal function in asymptomatic younger individuals is not clear. The aim of this study was to determine the association between plasma homocysteine and renal function in a biracial (black-white) community-based cohort of asymptomatic young adults. #### Methods Used Plasma homocysteine along with cardiovascular disease risk factor variables were measured in 805 white and 330 black subjects, ages 24-44 years, enrolled in the Bogalusa Heart Study. Renal function was assessed by estimated glomerular filtration rate (eGFR). #### Summary of Results Males vs females showed higher homocysteine levels (8.83 ± 3.16 vs 7.35 ± 2.84 µmol/L, *P* < 0.0001) and lower eGFR (99.1 ± 17.6 vs 102.5 ± 21.0 mL/min/1.73m2, *P* = 0.024). Whites vs blacks had lower eGFR (97.3 ± 18.0 vs 110.0 ± 20.6 mL/min/1.73m2, *P* < 0.0001). In a multivariate regression analysis that included age, race, sex, body mass index, blood pressure, lipoprotein variables, insulin resistance index and homocysteine, white race (regression coefficient β = -0.291, *P* < 0.0001), age (β = -0.133, *P* < 0.0001) and homocysteine (β = -0.098, *P* = 0.0008), in that order, were independently associated with eGFR. The odds ratio (95% confidence interval) of individuals in the homocysteine quintiles II, III, IV and V vs I for having the risk of impaired eGFR defined as <10th percentile, specific for race, sex and age, was 2.28 (0.95-5.50, *P* = 0.065), 2.97 (1.24-7.12, *P* = 0.015), 3.32 (1.45-7.60, *P* = 0.005) and 6.99 (3.06-15.94, *P* < 0.0001), respectively. #### Conclusions Homocysteine is an independent correlate of renal function in asymptomatic black and white young adults. ### 212 RENAL FAILURE DUE TO LEUKEMIC INFILTRATION IN CHRONIC LYMPHOCYTIC LEUKEMIA: A CASE REPORT Z. Soltani, Av Jack, M.M. Bouyarden, S.A. Morse *LSU, New Orleans, LA*. #### Case Report The patient is a 49-year-old, white man from New Orleans who was diagnosed with chronic lymphocytic leukemia (CLL), with evidence of lymphocytosis and lymphadenopathy in August 2007 and was followed with observation alone. He was later referred to NIH for an investigational protocol where it was noted that the patient had abnormal serum creatinine of 1.8 in July 2008. Based on NIH preference, renal work-up was started at LSU before additional CLL investigation. At first visit, serum creatinine jumped to 2.4. Positive findings were history of night sweats; bulky cervical and subclavicular lymphadenopathy; and trace lower extremities edema. Comprehensive Laboratory tests were just remarkable for lymphocytosis, anemia, and trace proteinuria. Bilateral enlarged kidneys and caliectasis as well as retroperitoneal lymphadenopathy were seen in abdominal ultrasonography. The patient had a renal biopsy performed to help discern etiology of his progressive renal dysfunction, which revealed that the entire interstitium was densely infiltrated with a polymorphic population of lymphocytes. Immunofluorescence and electron microscopy were both negative for immune complexes. Because of developing hyperkalemia and oliguria, the patient was started on renal replacement therapy for one session as well as chemotherapy in August 2008. Combination chemotherapy consisting of monthly courses of cyclophosphamide, vincristine and prednisone and rituximab, resulted in a rapid improvement of the renal function and in an apparent hematological and clinical remission of the CLL. After 2 courses, during follow up, no deterioration of renal function has been noted. Conclusion: Acute renal dysfunction associated with chronic lymphocytic leukemia has a variety of causes. An extremely rare cause of renal dysfunction is diffuse leukemic infiltrate in the renal interstitium. However, it should be always considered in the differential diagnosis because it seems to respond reasonably well to a variety of therapies. The finding of enlarged kidneys on renal ultrasound is suggestive of infiltrative disease. ### 213 DELAYED RENAL GRAFT FUNCTION DUE TO RECURRENT FSGS C. Straatmann1, S. Florman2, V. Vehaskari1 * 1LSU Health Sciences Center, New Orleans, LA and 2Tulane University, New Orleans, LA*. #### Case Report Focal segmental glomerulosclerosis (FSGS) is known to recur in approximately 30% of transplanted kidneys, typically presenting with heavy proteinuria and initially unimpaired renal function. A circulating factor in the recipient is hypothesized to be responsible for the increased glomerular permeability, whereas progression into graft failure is thought to involve other factors such as progressive sclerosis. We present a case to support the notion that a circulating factor may also be responsible for delayed graft function. A 15-year old patient with collapsing FSGS received a kidney from her father after undergoing bilateral nephrectomy. Cold ischemia time was minimal and there were no surgical problems. Graft status was monitored by standard chemistries, urine protein/creatinine ratio (Upr/Cr, mg/mg), Doppler ultrasound and percutaneous biopsies. Delayed graft function with severe oliguria was evident from post-transplant day 1. By day 4 her s-Cr had risen from 9.0 to 11.3 mg/dL prompting initiation of hemodialysis. Her Upr/Cr was high on day 1 (4.2) and rose to 23-351 during the first month. Biopsies of the transplanted kidney on days 2, 10 and 30 showed diffuse fusion of the foot processes but no ATN or other injury. Doppler US showed good blood flow. Plasmapheresis treatments were begun on day 11 and continued with decreasing frequency for 6 months; earlier discontinuation attempts resulted in prompt recurrence of heavy proteinuria. She was able to discontinue dialysis 1 month post-transplant with improving graft function. After plasmapheresis was stopped at 6 months, her Upr/Cr has remained normal and s-Cr at 1.2-1.4 mg/dL. Follow-up biopsy still shows partial foot process fusion. The early onset of heavy proteinuria, unequivocal biopsy findings of extensive foot process fusion, absence of ATN and clear response to plasmapheresis strongly support the recurrence of FSGS as the etiology of the delayed graft function in this case, suggesting that pre-transplant plasmapheresis for removal of the putative circulating factor might be beneficial in aggressive FSGS. ## **Southern Society for Clinical Investigation and Southern American Federation for Clinical Research Plenary Session Young Investigator Award Finalists SAFMR/SSCI/ Young Faculty Award SAFMR/SSCI/ Trainee Research Award** 8:00 AM Friday, February 13, 2009 ### 214 ANTI-HUMAN DEATH RECEPTOR 5 INDUCED APOPTOSIS IN MOUSE CELL LINES BY A NOVEL HUMAN-MOUSE CHIMERIC MOLECULE J. Li1, P. Yang1, H. Hsu1, J. Mountz1,2 * 1University of Alabama at Birmingham, Birmingham, AL and 2VA Medical Center, Birmingham, AL*. #### Purpose of Study Death receptor 5 (DR5) is a pro-apoptotic protein considered as a key target for cancer therapy. An anti-human DR5 agonistic antibody, TRA-8, has been shown to induce apoptosis in various tumor cells and thus is regarded as one of the most promising therapeutic strategies. However, a mouse model that can be used to evaluate the TRA-8 therapeutic response is lacking. The purpose of this study is to generate a humanized mouse DR5 molecule that can be used to determine the mechanism of DR5 mediated apoptosis in a mouse using a therapeutic anti-human DR5 antibody. #### Methods Used A 1kb and a 3kb putative promoters, and a 3 kb first intron of mouse DR5 were subcloned upstream of a chimeric DR5 consisting of a human extracellular domain, a mouse transmembrane and an mouse intracellular domain. This enabled analysis of DR5 function in mouse cells with TRA-8. Transfection was performed by using Lipofectamine and nucleofection. Chimeric DR5 expression was determined by FACS and Western blot. Cell death was estimated by the ATPLite. #### Summary of Results The human/mouse (hu/mo) DR5 chimeric protein was successfully transported and targeted to the mouse cell membrane. Maximal expression was seen with the 1 kb promoter in NIH3T3 and 4T1 cells. Combination of longer promoter with first intron conferred authentic expression of chimeric DR5. Mouse promoter exhibited limited activity in human HEK293 cells. High expression of hu/mo DR5 resulted in high cell death in NIH 3T3 and 4T1 cells with less apoptosis in the anti-DR5 resistant L5178 cell. Human full-length DR5 induced low apoptosis in mouse cells. Crosslinking of the hu/mo DR5 with TRA-8 enhanced apoptosis with efficacy varying from 20% (shorter promoter, high DR5 expression) to 60% (longer promoter plus the first intron, authentic DR5 expression). #### Conclusions We generated and optimized a hu/mo DR5 molecule with essential regulatory elements that can enable authentic expression of DR5 and the induction of apoptosis by TRA-8 in mouse cells. This construct will lead to the generation of a novel transgenic mouse for analysis of the anti-human DR5 apoptosis mechanism, therapeutic response and DR5 expression regulation in both cancer and autoimmune diseases. ### 215 PEPSIN IN GASTRIC FLUID PROMOTES EPITHELIAL MESENCHYMAL TRANSFORMATION: IMPLICATIONS FOR UNDERSTANDING THE ROLE OF REFLUX IN PULMONARY FIBROSIS F. Ahmad1, J. Ritzenthaler1, J. Roman1,2 * 1Emory University, Atlanta, GA and 2VA Medical Center, Atlanta, GA* #### Purpose of Study Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease with an unknown cause. Patients with IPF often suffer from some form of gastroesophageal reflux disease (GERD), which can range from esophageal reflux to aspiration into the lung. Although GERD has been implicated in the pathogenesis of IPF, its role is controversial and the mechanisms involved in this association remain largely unexplored. Studies suggest that injury to lung epithelial cells might promote lung fibrosis. This process includes the transformation of epithelial cells into mesenchymal-type smooth muscle-like cells with augmented capacity for matrix remodeling and tissue contraction. Because of the perceived importance of this process, termed epithelial-mesenchymal transformation (EMT), we explored the relationship between GERD and EMT in vitro. #### Methods Used We tested the hypothesis that specific components of gastric fluid could stimulate EMT. Specifically, we explored the effects of gastric fluid (HCl with and without pepsin, pH 2.0) versus pepsin (a protein-degrading enzyme) alone on rat lung epithelial type II cells. We incorporated techniques that involved cell culture, western blot analysis for protein production, RT-PCR for RNA analysis, and zymography for detection of enzyme activity. #### Summary of Results We found that exposure to pepsin stimulated the expression of α-smooth muscle actin (αSMA), a marker of EMT. Interestingly, gastric fluid (pH 2.0) in the absence of pepsin failed to stimulate αSMA expression. Of note, pepsin-induced EMT was also associated with increased expression of fibronectin, an extracellular matrix glycoprotein implicated in injury and repair. Furthermore, we determined that pepsin induced the expression of gelatinolytic activity related to matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-7 (MMP-7). #### Conclusions Together, these in vitro observations suggest that pepsin stimulates lung epithelial cells to undergo EMT characterized by increased expression of αSMA, matrix glycoproteins, and matrix-degrading proteases, thereby providing a cellular mechanism by which chronic GERD can promote the progression of IPF, and unveiling potential targets for therapy. ### 216 ENDOGENOUS INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTECTS AGAINST APOPTOSIS & CARDIAC REMODELING AFTER ACUTE MYOCARDIAL INFARCTION A. Varma, F.N. Salloum, N.N. Hoke, B.W. Van Tassell, A. Abbate, G.W. Vetrovec *VCU Pauley Heart Center, Richmond, VA*. #### Purpose of Study Apoptosis & inflammation are two key pathological features of post-infarction remodeling. Interleukin-1 (IL-1) signaling is involved in both apoptosis & inflammation in response to ischemia. We hypothesized that during ischemia, IL-1 receptor antagonist (IL-1Ra), an endogenous IL-1 inhibitor, plays a protective role & therefore mice lacking the IL-1Ra gene (knock out - KO) would be more susceptible to apoptosis & adverse cardiac remodeling after acute myocardial infarction (AMI). #### Methods Used Seven KO mice & 8 age-matched wild-type (WT) mice underwent surgical ligation of the left coronary artery. All animals underwent transthoracic echocardiography before surgery & at day 7. Infarct size and cardiomyocyte apoptosis were measured using collagen staining & in situ detection of DNA fragmentation, respectively. #### Summary of Results Seven days after AMI, KO mice showed increased left ventricular end-diastolic diameter & end-systolic diameter with reduced fractional shortening vs WT mice [Figure]. An average of 5 aneurysmatic segments were seen in the KO mice vs 1 segment in the WT mouse (*P* = 0.010). KO mice also had a significantly larger area of scar (35 ± 2% vs 23 ± 2%, *P* = 0.009) & significantly greater cardiomyocyte apoptosis in the peri-infarct myocardium (9.5 ± 2.2% vs 1.9 ± 0.1%, *P* = 0.022) compared to WT mice. #### Conclusions Endogenous IL-1Ra protects cardiomyocytes from apoptosis, prevents adverse cardiac remodeling & aneurysm formation after AMI. The cardioprotective effect of endogenous IL-1Ra on apoptosis affirms a role for IL-1 signaling & the potential for IL-1 based treatment strategies to prevent heart failure after AMI. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F12.medium.gif) [Figure.](/content/57/1/301/F12) Figure.   ### 217 DIRECT PHARMACOLOGIC INHIBITION OF MYELOID DIFFERENTIATION FACTOR-88 AS A NOVEL THERAPEUTIC TARGET AFTER ACUTE MYOCARDIAL INFARCTION B.W. Van Tassell1, F.N. Salloum2, A. Varma2, N.N. Hoke2, A. Abbate2 * 1Virginia Commonwealth University, Richmond, VA and 2Virginia Commonwealth University, Richmond, VA*. #### Purpose of Study Experimental and clinical evidence confirm the role of inflammatory signalling in pathologic cardiac remodeling after acute myocardial infarction (AMI). Myeloid differentiation factor 88 (MyD88) is a naturally occurring protein that mediates the effects of multiple pro-inflammatory pathways, including interleukin-(IL)-1, IL-18, and the toll-like receptor family. IMG2005 is a novel oligopeptide that directly inhibits MyD88 homodimerization. We hypothesized that IMG2005 would prevent cardiac remodeling in a mouse model of AMI. #### Methods Used Fourteen ICR mice underwent permanent surgical coronary artery ligation. Mice received daily intraperitoneal injections of IMG2005 1 mg/kg (n = 7) or NaCl 0.9% (n = 7) for 14 days. Animals underwent transthoracic echocardiography at baseline, 7 days, and 14 days after surgery. #### Summary of Results IMG2005 attenuated left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) versus saline at 14 days (see figure). IMG2005 mice also exhibited partial inhibition of aneurysm score (3 vs 4, *P* < 0.05) and a trend towards improved survival (*P* = 0.06), but no observable changes in fractional shortening or ejection fraction at 14 days. #### Conclusions MyD88 inhibition with IMG2005 prevents unfavorable cardiac remodeling after experimental AMI in mice. To our knowledge, ours is the first model to investigate the effects of direct MyD88 inhibition in vivo. Pharmacologic inhibition of MyD88 may be a valuable therapeutic strategy in post-infarction remodeling and heart failure. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F13.medium.gif) [Figure.](/content/57/1/301/F13) Figure.   ### 218 PARATHYROIDECTOMY DECREASES SYSTOLIC AND DIASTOLIC BLOOD PRESSURE IN HYPERTENSIVE PATIENTS A.S. Heyliger1, J. Sharma2, C. Weber2, V. Tangpricha3 * 1Emory University, Altanta, GA; 2Emory University, Atlanta, GA and 3Emory University, Atlanta, GA* #### Purpose of Study To determine the effect of parathyroidectomy on systolic and diastolic blood pressure in hypertensive subjects with hyperparathyroidism. #### Methods Used Data was collected retrospectively from medical records from patients undergoing parathyroidectomy between 1997 and 2006. We evaluated changes in serum calcium, parathyroid hormone (PTH) and blood pressure prior to and 6 months after surgery. #### Summary of Results We observed an expected decrease in both parathyroid (PTH) and calcium levels after parathyroidectomy. Hypertensive subjects experienced significant decreases in systolic blood pressure (SBP) from 153.2 ± 11 mmHg to 141 ± 18 mmHg (*P* < 0.001) and diastolic blood pressure (DBP) from 94.8 ± 6.0 mmHg to 83.4 ± 14.0 mmHg. A subgroup analysis revealed that subjects with primary hyperparathyroidism experienced a significant decrease SBP (152.5 ± 10.5mmHg to 140.3 ± 16.2 mmHg) and DBP (94.5 ± 6.8 mmHg to 81.7 ± 10.3 mmHg, *P* < 0.01). No significant changes in blood pressure were observed in secondary or tertiary hyperparathyroidism subjects. #### Conclusions This retrospective study suggests that parathyroidectomy in hypertensive subjects with primary hyperparathyroidism may be beneficial in reducing blood pressure. The presence of hypertension may be another indication for parathyroidectomy in these patients. ## **Southern Society for Pediatric Research Plenary Session Young Investigator Award Finalists** 8:00 AM Friday, February 13, 2009 ### 219 NIRS USED AS A TOOL TO EVALUATE SPLANCHNIC PERFUSION IN PRETERM INFANTS WITH NEC J. Moore1,2, S. Roark2, T. Nasr3,1 * 1Emory University, Atlanta, GA; 2Children's Healtcare of Atlanta, Atlanta, GA and 3Phoenix Children's Hospital, Phoenix, AZ*. #### Purpose of Study Necrotizing entercolitis (NEC) is a significant cause of morbidity and mortality in the neonatal intensive care unit. Decreased perfusion to the intestines may contribute to its pathophysiology, as well as possibly represent that intestinal tissue is necrotic. Near Infrared Spectroscopy (NIRS) is a noninvasive procedure which can measure regional oxygenation by measuring and continuously recording the weighted average of arterial and venous saturations. Our objective was to determine if preterm infants with NEC had significantly different abdominal NIRS values compared to matched controls that did not have NEC but were equally ill. #### Methods Used Prospective analysis of 20 preterm infants (10 infants with Bells stage II or higher NEC, 10 matched controls) who were greater than 1000 g and transferred to a referral children's hospital NICU in Atlanta for possible surgical evaluation. Exclusion criteria were major congenital anomalies including genetic, abdominal wall defects, cardiac anomalies, and infants offered comfort care only. Continuous abdominal NIRS measurements were done for up to 24 hours prior to going to the OR and were compared to cerebral NIRS for internal reference on each patient. #### Summary of Results In the NEC subgroup we found that there was 1) A statistically lower abdominal NIRS value compared to infants with septic shock and no abdominal process, 2) A trend towards matching the worse findings at surgery and the lowest abdominal NIRS values, 3) A real time recording of a perforation due to NEC. #### Conclusions Our study demonstrates the ability of NIRS to differentiate between infants with surgical NEC and infants that have septic shock and a process other than an abdominal insult. Ongoing studies are evaluating if NIRS is a tool that in the NICU may have a role in helping to determine when to operate on infants with NEC, and can it tell us how much bowel rest is sufficient after medical NEC prior to initiating refeeds. ### 220 EARLY USE OF AMINO TERMINAL PRO B-TYPE NATRIURETIC PEPTIDE IN DIAGNOSIS OF PATENT DUCTUS ARTERIOSUS IN VERY LOW BIRTH WEIGHT INFANTS J.K. Stamps, V. Joshi, G. Wetzel, R. Kudumula, A. Talati *University of Tennessee, Memphis, TN*. #### Purpose of Study A hemodynamically significant PDA (hsPDA) can cause significant morbidity in VLBW infants, particularly if treatment is delayed. N-terminal pro-brain natriuretic peptide (NT-proBNP) is one of a class of protein produced by cardiac myocytes in response to stretch and ia an effective marker for heart failure in adults. We evaluated the use of serum NT-proBNP levels to predict the presence of hsPDA in VLBW infants. #### Methods Used This is a prospective observational study with all neonates at a single level 3 NICU weighing <1250 gm eligible for enrollment. Infants with other congenital cardiac defects and imminent death were excluded. Informed consent was obtained from each patient's legal guardian. Demographic and clinical data gathered for the duration of the study. NT-proBNP levels were drawn on day 2 of life (24-48 h of age), and then every other day until day 10. Echocardiograms were done on day 2 of life within 4 h of serum NT-proBNP levels. Standard echocardiographic measurements for determining the presence of hsPDA were performed. A pediatric cardiologist blinded to the NT-proBNP levels or patient's clinical status reviewed the echocardiograms. The severity of shunting across PDA was categorized as none, mild, moderate, or severe. The initial levels of NT-proBNP were compared with severity of shunting using Spearman's correlation with statistical significance at *P* <.05. #### Summary of Results Twenty infants have been enrolled so far, with mean BW of 856 ± 146 gm and mean EGA 27 ± 1 wk. On echocardiographic findings, 4 infants had no shunt across the PDA, 8 infants had mild and 8 with moderate shunt, with none having severe shunts. The mean postnatal age of serum NT-proBNP level was 37 ± 4 h. The level of NT-proBNP increased with level of shunt and was 5845 ± 1952 (no shunt), 14815 ± 5358 (mild shunt), 24028 ± 3685 pg/ml (moderate shunt) respectively (mean ± SEM) (*P* = 0.005). The PDA color diameter significantly correlated with rising NT-proBNP levels (*P* = 0.02). All infants in moderate shunt group received indomethacin therapy in the first week while none of the patients without shunt received indomethacin. #### Conclusions We conclude that early NT-proBNP levels increase with a significant shunt across the PDA and can be used to determine the status of shunt across the PDA. ### 221 CORRELATION OF BRAIN TISSUE OXYGENATION WITH CEREBRAL NIRS AND SYSTEMIC SVO2 DURING VA ECMO IN A PORCINE MODEL K. Tyree, M.M. Tyree, R. DiGeronimo *Wilford Hall Medical Center, San Antonio, TX*. #### Purpose of Study ECMO patients are at risk for brain injury & associated neurologic impairment. There's a need to target therapeutic interventions to improve neurologic outcomes in ECMO survivors. During VA ECMO, systemic oxygen sufficiency is commonly followed using SVO2 monitoring. Many centers are now using near infrared spectroscopy(NIRS) to better assess cerebral saturation. How well NIRS & SVO2 values actually correlate with brain tissue oxygen on VA ECMO during and following systemic hypoxia is unclear. Objective: Using the in situ brain tissue partial pressure oxygenation(BtO2) as the standard: Compare the BtO2 with NIRS & SVO2 during VA ECMO in a porcine model. Hypothesis: Both NIRS & SVO2 would correlate with BtO2. Additionally, NIRS would have a stronger correlation than SVO2 with BtO2. #### Methods Used Immature piglets(n = 12) were placed on VA ECMO. Direct brain BtO2(Licox®) was measured via a surgically implanted cerebral catheter placed in the superficial cerebral cortex. Cerebral saturation was monitored non-invasively using regional NIRS(rSO2 index; Somanetics®), and SVO2 was measured from the circuit venous return(CDI 500, Terumo®). Post stabilization, animals were subjected to gradual systemic hypoxia followed by gradual recovery during which BtO2, NIRS and SVO2 were recorded at five minute intervals. Data were analyzed with Linear Regression, T-test, and Mann Whitney Rank Sum Test using the SigmaStat® Program. #### Summary of Results While the correlation between NIRS & BtO2 was marginally higher than the correlation between SVO2 & BtO2 (R2 = 0.32 and 0.26 respectively), overall both had poor correlation with BtO2. NIRS did correlate well with SVO2 particularly at baseline and as hypoxia occurred (R2 = 0.75). We also observed that one third of our study animals followed a different recovery pattern where the SVO2 rapidly recovered to baseline while the NIRS & BtO2 lagged behind. A subgroup analysis showed these animals were statistically physiologically different with lower mean blood pressure, lower pH, higher serum lactate levels, and that NIRS correlated better with BtO2 (R2 = 0.76). #### Conclusions Non-invasive NIRS monitoring may serve as a useful adjunct in assessing adequacy of cerebral oxygenation during VA ECMO, especially following recovery from hypoxia in piglets that were more hypotensive & acidotic. ### 222 THE ONTOGENY OF INSULIN SIGNALING IN THE PREMATURE BABOON MODEL C. Blanco1, R. DeFronzo2, N. Musi2 * 1University of Texas Health Science Center, San Antonio, TX and 2University of Texas Health Science Center, San Antonio, TX*. #### Purpose of Study Transient neonatal hyperglycemia is reported in 80% of extremely premature infants and it is thought to be a consequence of insulin resistance in peripheral tissues such as skeletal muscle and liver. Nonetheless, neither the tissues, nor the molecular basis for insulin resistance of prematurity have been defined. We hypothesized that the insulin transduction pathway is not fully developed in the immature baboon suggesting a role in the pathophysiology of transient neonatal hyperglycemia. #### Methods Used We studied fetal baboons because they have 97% phylogenetic proximity with humans and develop hyperglycemia when delivered prematurely. Fetal baboons were delivered prematurely via elective c-section at 125d gestational age (GA), 140d GA, or near term at 175d GA (fullterm = 185d GA) and necropsied immediately after birth. Quadriceps muscle and liver tissues were obtained and protein expression of insulin signaling proteins [insulin receptor substate-1 (IRS-1), the p85 subunit of phosphatidylinositol 3-kinase (p85), glucose transporter protein (GLUT) 1, GLUT4, Akt and AS160] were measured by Western blotting. #### Summary of Results The muscle of 125d GA fetal baboons had markedly lower GLUT1 protein expression (8% of 140d GA and 7% of 175d GA fetuses, *P* < 0.01). GLUT4 protein was also reduced in the fetal muscle at 125d GA (50% of 175d GA, *P* < 0.01). These reductions in GLUT1 and GLUT4 in 125d GA fetuses were accompanied by lower expression of the Rab GAP AS160 (35% of 175d GA, *P* < 0.01). IRS-1 and p85 protein content were unchanged in muscle in premature animals. Interestingly, Akt expression was 2.7-fold and 9.6-fold higher in the muscle from the 125d GA baboons when compared to 140d (*P* < 0.01) and 175d GA fetuses (*P* < 0.001) respectively; this may represent a compensatory mechanism to offset the insulin resistance, or may be related to the rapid cell growth that occurs during fetal development. No differences were found in the expression of insulin signaling proteins in liver. #### Conclusions (1) reduced expression of key glucose-transport regulating proteins (GLUT1, GLUT4, AS160) in muscle may be involved in the pathogenesis of neonatal hyperglycemia and insulin resistance; 2) baboons are a novel and clinically relevant model for the study of neonatal insulin resistance/hyperglycemia. ### 223 ECMO-RELATED SYSTEMIC INFLAMMATORY RESPONSE IS ASSOCIATED WITH ENTEROCYTE INJURY AND INCREASED CIRCULATING BACTERIAL PRODUCTS A. Kurundkar1, J. Timpa3, B. McIlwain3, C. Killingsworth2, A. Maheshwari1 * 1UAB, Birmingham, AL; 2UAB, Birmingham, AL and 3UAB, Birmingham, AL*. #### Purpose of Study Neonates treated with ECMO frequently develop a Systemic Inflammatory Response Syndrome (SIRS). Because gut mucosal injury is frequently noted in autopsies on neonates who died on ECMO, we used our piglet model of venoarterial (VA) ECMO to investigate the hypothesis that abnormal gut barrier function and bacterial translocation play an important role in ECMO-related SIRS. #### Methods Used Healthy 8-12 lb piglets (n = 5) were ventilated and placed on VA ECMO for 8 hrs. Sham animals (n = 5) were cannulated and provided ventilation. Plasma levels of bacterial products (LPS, D-lactate, and lipoteichoic acid), cytokines (TNF-α, IL-8, IL-6, and IL-1β), and intestinal-fatty acid binding protein (I-FABP, a marker of enterocyte injury) were measured by ELISA. Expression of 55 inflammatory genes was measured by a qPCR array. Neutrophil activation markers and T cell fas ligand expression was measured by FACS. Enterocyte apoptosis was measured by TUNEL and the involved mechanisms were investigated by qPCR and immunohistochemistry. #### Summary of Results Inflammatory changes (elevated plasma TNF-α) started with in the 1st hour on ECMO and were measurable as histopathological changes, increased cytokine levels, and neutrophil activation. Plasma I-FABP levels were elevated during ECMO, indicating enterocyte injury, which was confirmed in tissue sections. Plasma LPS (0.5 ± 0.05 U/mL and 0 in ECMO vs. sham), D-lactate, and lipoteichoic acid were elevated within 1 hr of ECMO. TUNEL showed widespread enterocyte apoptosis, which was confirmed by caspase-8 staining as mediated by the extrinsic apoptotic pathway. Fas ligand (FASL) was identified in our qPCR array as the likely activator of the extrinsic pathway and was immunolocalized to T-cells in the lamina propria. FASL colocalized with 8-hydroxydeoxyguanosine, a marker of oxidative damage. Treatment of T-cells with H2O2 in vitro increased FASL expression, indicating a mechanistic role for reactive oxygen species (ROS). #### Conclusions In our neonatal porcine model of VA ECMO, the onset of SIRS is associated with enterocyte injury and increased circulating bacterial products. ROS-activated T-cells likely play an important role in the development of enterocyte injury and the loss of gut barrier function. ### 224 REACTIVE OXYGEN SPECIES ARE INTEGRAL IN EPITHELIAL-MESENCHYMAL TRANSITION OF ALVEOLAR EPITHELIAL CELLS S. Vyas-Read, T. Gauthier, L. Brown *Emory University, Atlanta, GA*. #### Purpose of Study The persistence of myofibroblasts is associated with the progression of interstitial lung diseases (ILD) such as bronchopulmonary dysplasia. A significant source of myofibroblasts is the epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AEC) that are exposed to transforming growth factor-β1 (TGF-β1). In non-alveolar cells, TGF-β1 increases reactive oxygen species (ROS) and decreases antioxidants. Conversely, ROS have been shown to increase TGF-β1. ROS are elevated in lung tissue of ILD patients but the role of ROS in alveolar EMT is unknown. We hypothesized that 1)ROS are integral to TGF-β1-induced alveolar EMT and that 2)ROS increase TGF-β1 in AEC. #### Methods Used To assess the role of ROS in TGF-β1-induced EMT, RLE-6TN were cultured with TGF-β1 (2ng/mL) or with TGF-β1 plus either a NADPH oxidase inhibitor (dibenziodolium chloride, DPI 5 μM) or an antioxidant (glutathione, GSH 500 μM). The ability of ROS to induce EMT was assessed using hydrogen peroxide treatment (H2O2 100 μM). Immunofluorescence for the myofibroblast marker, alpha-smooth muscle actin (α-SMA), and the epithelial marker, E-cadherin (E-cad) was performed to assess alveolar EMT. The effect of ROS on TGF-β1 was assessed in H2O2-treated AEC by evaluating TGF-β1 and phosphorylated-smad3 expression (phospho-smad3, a marker of TGF-β1 signaling). #### Summary of Results TGF-β1-treated AEC had increased α-SMA expression, lost E-cad expression and acquired a fibroblast-like shape compared to control AEC. In contrast, TGF-β1-exposed AEC treated with DPI or GSH expressed less α-SMA and retained an epithelial shape. AEC treated with TGF-β1 plus GSH maintained E-cad expression at control levels. H2O2-exposed AEC had increased α-SMA, decreased E-cad and developed a stellate shape similar to TGF-β1-treated AEC. H2O2-exposed AEC also expressed increased TGF-β1 and phospho-smad3 compared to control cells. #### Conclusions ROS are integral to TGF-β1-mediated alveolar EMT and ROS increase TGF-β1 in AEC. The alveolar epithelium that is exposed to TGF-β1 and ROS in ILD may be susceptible to EMT. An enhanced understanding of these mechanisms may allow for the development of new therapies for ILD. ## **Southern Society for Clinical Investigation and International Academy of Cardiovascular Sciences - NA Chapter Joint Session I Young Clinician Scientist Award Competition Plenary Session Young Investigator Award Finalists** 12:30 PM Friday, February 13, 2009 ### 225 C-REACTIVE PROTEIN DRIVES INFLAMMATORY MEDIATOR EXPRESSION IN ACUTE VASCULAR INJURY F. Hage, S. Oparil, W. Feng, D. Xing, Y. Zhang, M. McCrory, Y. Chen, A. Szalai *UAB, B'ham, AL* #### Purpose of Study In human C-reactive protein transgenic mice (CRPtg) neointima formation 4 wks after vascular injury is exaggerated compared to non-transgenic mice (NTG). To elucidate the mechanisms by which CRP exacerbates the response we studied the early expression of inflammatory mediators (cytokines, selectins, chemokines, integrins and FcγRs) by the injured vessel. #### Methods Used The common carotid arteries of n = 10 CRPtg and n = 10 NTG were surgically exposed and the right carotid arteries ligated. The arteries were harvested 24 h later, mRNA was extracted from 5 pairs of injured and 3 groups of uninjured arteries (3 or 4 arteries per group), and RT-PCR performed. #### Summary of Results Expression of the chemokine MCP-1 and cytokine TNFα was higher in injured CRPtg arteries than in any other treatment or genotype group. In contrast IL-6 and IL-8 expression was increased by injury, but about equally in both genotypes, whereas expression of the adhesion molecules ICAM and VCAM were not affected by injury. mRNAs for all 3 FcγRs were detected in NTG and CRPtg arteries. Expression of FcγRIIb was unaffected by injury, while FcγRI and FcγRIII showed exaggerated expression in CRPtg. FcγRI expression increased by more than 4-fold in CRPtg compared to treatment matched NTG (Fig). ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F14.medium.gif) [Figure.](/content/57/1/301/F14) Figure.   #### Conclusions The local early expression of FcγRI is greatly exaggerated in CRPtg following acute vascular injury, suggesting the FcγRI-dependence of the CRP exacerbating effect we earlier observed at 4 wks after injury is due to a tissue response initiated soon after injury. ### 226 ZINC DYSHOMEOSTASIS IN RATS WITH CHRONIC ALDOSTERONISM. RESPONSE TO ZINC SUPPLEMENT M.S. Gandhi, P.A. Deshmukh, G. Kamalov, T. Zhao, M. Zhao, J.R. Tichy, S.K. Bhattacharya, R.A. Ahokas, Y. Sun, I.C. Gerling, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN*. #### Purpose of Study Increased Zn2+ excretion and Zn2+ translocation from plasma to injured tissues, including the heart, each accompany aldosteronism (inappropriate for dietary Na+ intake). Likewise, excretory Ca2+ losses contribute to plasma ionized hypocalcemia and secondary hyperparathyroidism (SHPT) with subsequent intracellular [Ca2+]i overloading, the induction of oxidative stress, and the appearance of cardiac pathology. Herein, we addressed Zn dyshomeostasis in 8-wk-old male Sprague-Dawley rats receiving aldosterone/salt treatment (ALDOST) alone or together with a Zn2+ supplement based on the hypothesis intracellular [Zn2+]i is an antioxidant. #### Methods Used We monitored: 1) Zn2+ levels in the heart; cardiomyocyte cytosolic free [Zn2+]i and mitochondrial [Zn2+]m; the expression of metallothionein (MT-1), a Zn binding protein; and biomarkers of oxidative stress; and 2) the effect of ZnSO4 supplement (40 mg/day by gavage) on oxidative stress and cardiac pathology. #### Summary of Results Compared to age-/gender-matched controls, at 4 wks ALDOST we found: a rise (*P* < 0.05) in cardiac Zn2+ that included increased [Zn2+]i and mitochondrial [Zn2+]m, associated with increased (*P* < 0.05) tissue MT-1, 8-isoprostane, malondialdehyde, and gp91phox, coupled with oxidative stress in plasma and urine; and ZnSO4 prevented (*P* < 0.05) hypozincemia, but not ionized hypocalcemia, and therefore it only attenuated oxidative stress and microscopic scarring without preventing the vasculitis and perivascular fibrosis of intramural coronary arteries, each of which represent pathologic remodeling of the heart associated with SHPT in ALDOST. #### Conclusions Thus, the oxidative stress that appears in the heart in response to prooxidant intracellular Ca2+ overloading during ALDOST is accompanied by increased tissue Zn serving as an antioxidant. Cotreatment with ZnSO4 attenuated but did not prevent cardiomyocyte necrosis. A supplement that includes Zn2+ and Ca2+ may be required to counteract the dyshomeostasis of both cations that accompanies aldosteronism and the relative balance between them which determines the appearance of cardiac pathology. ### 227 BETA-LACTAM ALLERGY AND MYOCARDIAL ISCHEMIA (KOUNIS SYNDROME) C. Cevik1, M. Ridella1, S. Bagdure2, K. Nugent1 * 1Texas Tech University Health Sciences Center, Lubbock, TX and 2Texas Department of State Health Services, Lubbock, TX*. #### Purpose of Study Patients with anaphylaxis can have acute coronary syndromes secondary to allergic mediator effects on coronary vessels. These patients require dual management strategies. #### Methods Used We identified all cases in the PubMed database in English with searches using beta-lactams\adverse effects and several coronary disease MeSH terms. #### Summary of Results We reviewed 17 cases with a median age of 60 (range 13 to 72). Seventy-six percent of the patients were men. The beta-lactam antibiotic was administered by an oral route in 8, an IV route in 8, and intramuscular route in 1. Thirteen patients had cutaneous reactions, 7 had respiratory symptoms, 2 had GI symptoms, 11 had chest pain, and 12 had hypotension. All reactions except one developed within 30 minutes. Ten patients had an elevated troponin levels. ECG revealed ST segment elevation in all patients except one. Cardiac catheterization was normal in 10 patients and abnormal in 5 patients. Allergy testing identified 4 patients with positive skin tests to antibiotics, 4 with increased IgE levels, 3 with increased histamine levels, 3 with increased tryptase levels, and 1 with a positive leukocyte transformation test. Treatment included epinephrine (n-4), corticosteroids (n-13), H1 blockers (n-12), H2 blockers (n-6), morphine (n-2), nitroglycerine (n-8), and aspirin (n-3). Twelve patients had a Kounis type 1 syndrome (primarily vasospasm) and 5 patients had a Kounis type 2 syndrome (occult coronary disease). All patients survived. #### Conclusions Patients with anaphylaxis can present with acute coronary syndrome secondary to either vasospasm or acute plaque rupture and thrombus formation. The typical patient is a man with cutaneous, respiratory and cardiac symptoms. The ECG reveals ST segment elevation in inferior leads. Management should include therapy for anaphylaxis and vasospasmolytics. The use of epinephrine requires caution. ### 228 DESENSITIZATION THERAPY IS ASSOCIATED WITH IMPROVED SURVIVAL TO TRANSPLANT IN SENSITIZED PATIENTS BRIDGED WITH A LEFT VENTRICULAR ASSIST DEVICE K. Singh1, P. Patel1, C. Ayers1, E. Seglem2, C. Fitzsimmons1, P. Kaiser1, M. DiMaio1, S. Ring1, C. Yancy2, P. Mammen1, D. Meyer1, M. Drazner1, D. Markham1 * 1UT Southwestern, Dallas, TX and 2Baylor Medical Center, Dallas, TX*. #### Purpose of Study Patients bridged to transplant with left ventricular assist devices (LVAD) are often sensitized as measured by panel reactive antibodies (PRA). This study evaluates whether immunomodulatory therapy of sensitized LVAD patients improves survival to transplant. #### Methods Used A review of the UT Southwestern/Baylor University Medical Center Transplant Database identified 87 patients who received an LVAD as a bridge to transplant between 1990-2008. Patients were excluded from the study if they died (n = 14) or were transplanted (n = 13) within 30 days of LVAD placement, or if they did not have a measured PRA (n = 2) leaving a cohort of 58 patients. Sensitization was defined as PRA >10%. Immunomodulation (various combinations of cyclophosphamide, IVIG, MTX, MMF, or immunoadsorption) was administered to sensitized patients based on physician discretion. #### Summary of Results 31 (53%) patients were not sensitized and 27 (47%) were sensitized. Of the sensitized patients, 10 (37%) were treated and 17 (63%) were not treated. The sensitized/treated and sensitized/untreated groups had similar median wait times until transplant (211 vs. 197 days, *P* = 0.4). However, sensitized/treated patients vs. sensitized/untreated patients had a greater mean PRA reduction (47% vs. 22%, *P* = 0.04) and improved survival to transplant (100% vs. 65%, *P* = 0.04). There were no significant differences in survival to transplant between the not sensitized group and the sensitized/treated or sensitized/untreated groups. #### Conclusions Treatment of sensitized patients was associated with improved survival to transplant in a two center retrospective study. Further prospective studies evaluating the benefits of desensitization are needed. ## **Adolescent Medicine and Pediatrics Concurrent Session** 2:00 PM Friday, February 13, 2009 ### 229 PAIN MEASUREMENT USING VIDEOTAPE REVIEW COMPARED TO PATIENT SELF-REPORT A. Turner1, S. Spanos2, K. Black1, K. Sikes1, E. Gracely3, I. Kim1 * 1University of Louisville, Louisville, KY; 2University of Cincinnati, Cincinnati, OH and 3Drexel University, College of Medicine, Philadelphia, PA* #### Purpose of Study Accurate tools for assessing pain are critical for developing and evaluating pain control techniques. Videotape review has been utilized in the analysis and comparison of pain measures in children. However, there is little data in children about the accuracy and reliability of videotape review pain scoring. The objective of this study was to assess the validity of videotape review as a tool for evaluating the pain of peripheral intravenous catheterization (PIVC) experienced by children. #### Methods Used A convenience setting of 68 children in the emergency department of an urban, tertiary care hospital were enrolled in this prospective, observational, double-blind trial. Three blinded physicians independently reviewed videotapes of patients undergoing PIVC insertion. Each observer rated the patients' pain based on videotape review by assigning a visual analogue scale (VAS) score. The observers were blinded to the type of anesthesia administered to each patient prior to the procedure as well as to the patients' self-report VAS scores. The observers' VAS scores were compared with the patients' VAS scores for the same procedure. The three observers' scores were also compared with one another to determine reproducibility of VAS scores after videotape review. #### Summary of Results Using Spearman's rho, weak to moderate correlation was demonstrated between the physician observers' VAS scores and the patients' self-reported VAS scores with Spearman's rho of 0.412-0.504. Moderate correlation was demonstrated among the blinded observers' VAS scores with Spearman's rho of 0.517 - 0.837. Interclass correlation coefficients for the physician observers were 0.492 - 0.602. #### Conclusions Videotape review of children's pain while undergoing PIVC placement did not accurately measure pain. Patient self-report of pain may still be the best measurement of patient pain. ### 230 TRUST IN PEDIATRICIAN IMPROVES ANTICIPATORY GUIDANCE IN A PRIMARY CARE CLINIC DZ Kuo1, CS Minkovitz2 * 1University of Arkansas for Medical Sciences, Little Rock, AR and 2Johns Hopkins University, Baltimore, MD*. #### Purpose of Study Trust is regarded as integral to the caregiver-pediatrician relationship. Little is known about the change over time in caregiver trust in pediatricians, and whether trust is associated with receipt of anticipatory guidance in primary care settings and related parenting practices. The objectives of the study were (1) to examine the change over time in trust between parent and a pediatrician in a primary care setting, and (2) to examine the association of trust with receipt of anticipatory guidance and following of recommended parenting practices. #### Methods Used Prospective cohort study in an urban primary care clinic with pediatric residents. Caregivers were enrolled at the two month well child visit and completed surveys at 2 and 4 months. Surveys contained 2 trust scales, the Pediatric Trust-in-Physician Survey (range 11-55) and the abbreviated Patient Trust in the Medical Profession (range 5-25). Parents were asked about anticipatory guidance received during the well child visits. At 4 months, parents additionally reported on 6 parenting practices. #### Summary of Results 100 families enrolled at the two month visit, and 75 completed four month surveys. Trust in the physician rose between the two and four month visit (45.9 versus 48.5; *P* <.01). Following of ≥4 of 6 previously recommended parenting practices by the four month visit was associated with a higher trust in the medical profession (20.9 versus 18.6; *P* <.01). Discussion of all six recommended parenting practices during the four month visit was associated with a higher trust in the provider score (50.0 versus 46.4; *P* <.05). Fewer emergency department visits were associated with greater trust in physician. No difference in outcomes were seen when analyses were stratified by the same caregiver-pediatrician dyad between the two and four month visits. #### Conclusions Trust in pediatricians may improve delivery of anticipatory guidance in the primary care setting. Parental trust of their child's physician increases with time, and increased trust is associated with more anticipatory guidance discussed, following of recommended parenting practices and decreased emergency department utilization. Consistent caregiver-pediatrician dyads may not be essential for delivery of anticipatory guidance. ### 231 CALCIUM-CHANNEL BLOCKERS VS. ACE INHIBITORS FOR PEDIATRIC HYPERTENSION T.C. Wall1, J. Beall2, M.R. Benfield1 * 1University of Alabama at Birmingham, Birmingham, AL and 2Samford University, Birmingham, AL*. #### Purpose of Study; To compare the effectiveness of calcium channel blockers (CCB) to angiotensin-converting enzyme (ACE) inhibitors as monotherapy in the treatment of pediatric hypertension (HTN). #### Methods Used Charts were reviewed retrospectively for children ages 6 -18 years evaluated in the nephrology clinic May 2000 - February 2007 for HTN and had at least one follow-up visit and were started on anti-hypertensive medications during in the subsequent 12 months. Patients who were on antihypertensive medications prior to their 1st visit were excluded. We abstracted up to three visits defined as "visit 1″ (initial), "visit 2″ (at 2 to 6 months), and "visit 3″ (at 9 to 12 months follow-up). Bivariate analyses were performed using Chi-square statistics. #### Summary of Results 71 patients met inclusion criteria; mean patient age was 13.8 years. Half (51%) were male, 56% white, 42% black, 35% had Medicaid coverage. Most patients were overweight; 66% had a BMI >95th percentile. The mean number of follow-up visits per patient was 2.7 (range 1 to 6). Baseline BPs were classified as <95th %ile (8, 12.7%), stage 1 HTN (26, 36.6%), and stage 2 HTN (36, 50.7%). Newly prescribed medications at visit 1 included 57 ACE inhibitors, 9 CCBs, and 4 beta-blockers. Sixty-five patients returned for visit 2, 53 from the ACE inhibitor group and 8 from the CCBs. Only 1/8 CCB recipients had adequate BP control at visit 2, compared to 33/53 of ACE inhibitor treated patients (*P* < 0.05). However, 4/8 CCB patients and 8/53 ACE inhibitor patients had been changed to another medication since visit 1. Examining BP control by current medications at visit 2 (monotherapy only), 2/7 patients on CCB and 30/45 patients on ACE inhibitors had adequate BP control (*P* < 0.1). At visit 3, 21/24 original ACE inhibitor patients had adequate BP control, compared to 0/2 in the CCB group (*P* < 0.05). BP control by current medications (monotherapy) at visit 3 showed that 0/2 patients receiving CCB alone vs. 18/19 patients receiving ACE inhibitor alone had adequate control (*P* < 0.05). #### Conclusions ACE inhibitors appear to be the preferred first line antihypertensive medications in this setting. Although many patients experience a change in medication over time, patients started on ACE inhibitors appear to achieve better BP control at follow-up. ### 232 CHILD HEALTH, FAMILY NEEDS, AND HEALTH CARE RESOURCE OUTCOMES OF FAMILY-CENTERED CARE FOR CHILDREN WITH SPECIAL HEALTH CARE NEEDS D.Z. Kuo, T.M. Bird, J.M. Tilford *University of Arkansas for Medical Sciences, Little Rock, AR*. #### Purpose of Study Family-centered care is recognized as the standard of practice for children with special health care needs (CSHCN). Health services outcomes associated with family-centered care have not been well demonstrated for this population. The objectives of this study were to measure associations of family-centered care with (1) child health outcomes, (2) family needs, and (3) health care resource use for CSHCN. #### Methods Used Secondary analysis of the 2005-06 National Survey of Children with Special Health Care Needs (NS-CSHCN). Overall receipt of family-centered care was assessed by combined responses to five questions assessing elements of family-centered care. Chi-square and logistic regression examined associations of family-centered care with child health, family needs, and health care resource use. Propensity score matching methods were used to adjust for selection bias using predisposing, enabling, and need characteristics. All analyses accounted for the complex survey design of the NS-CSHCN. #### Summary of Results Family-centered care was reported by 65.6% of respondents. Family-centered care was associated with increased stability of health care needs (AOR 1.11, 95% CI 1.01, 1.22), less delayed care (AOR 0.66, 95% CI 0.55, 0.78), fewer unmet service needs (AOR 0.50, 95% CI 0.44, 0.57), fewer hours required for care coordination (AOR 0.87, 95% CI 0.79, 0.99), and less need for additional income (AOR 0.70, 95% CI 0.62, 0.79). Family-centered care was also associated with reduced likelihood of any ER visit in the previous 12 months (AOR 0.90, 95% CI 0.81, 0.99), but higher odds of ≥4 doctor visits (AOR 1.34, 95% CI 1.22, 2.16). #### Conclusions Consistent application of family-centered care practices for CSHCN may improve child health and reduce family burdens. Family-centered care may also reduce emergency room visits while increasing the number of outpatient visits. Further research should examine specific family-centered practices associated with desired child, family, and health system outcomes. ### 233 DOES VITAMIN D DEFICIENCY LEAD TO AN INCREASE RISK OF FRACTURES, SLIPPED CAPITAL FEMORAL EPIPHYSIS, AND BLOUNT'S DISEASE IN OVERWEIGHT YOUTH? C. Montgomery1, K. Young2, M. Ilyas2, M. Austen2, C. Jo2, R.D. Blasier1 * 1University of Arkansas, Little Rock, AR and 2University of Arkansas, Little Rock, AR*. #### Purpose of Study Poor dietary habits and decreased outdoor activity has led to an epidemic of overweight children. Along with this problem of obesity has come vitamin D deficiency. The lack of vitamin D alters the regulation of bone development and mineralization by diminishing physiological levels of calcium and phosphorus. Given vitamin D's known role in bone and growth plate mineralization and regulation, we hypothesize that vitamin D deficiency will lead to higher rates of fractures, slipped capital femoral epiphysis (SCFE) and Blount's disease. #### Methods Used Retrospective chart review of the Arkansas Children's Hospital (ACH) Pediatric Fitness Clinic database identified 890 patients. Data obtained included body mass index (BMI), vitamin D levels (25-vitamin D), and history of fractures, Blount's Disease, and/or SCFE. Patients were categorized into three vitamin D levels; very low (<15 ng/ml), low (16-32 ng/ml), and normal (>32 mg/ml). Statistical analysis of the data collected was performed using Pearson's chi-square and multiple logistic regressions. #### Summary of Results Blount's Disease was found to have a statistically significant (*P* < 0.05) positive correlation with patient's gender, BMI, and vitamin D level. Specifically, males were 8 times more likely than females to be observed with Blount's disease (*P* = 0.0079, CI = 1.731,38.283). Patients with very low vitamin D levels were 6.324 times more likely to have Blount's disease than patients with normal levels (*P* = 0.0078, CI = 0.749,53.373). Each whole number increase in BMI increases the likelihood of Blount's disease by 3.2% (*P* = 0.0152, CI = 1.006, 1.059). No significant associations between vitamin D levels and fractures or SCFE were found. #### Conclusions As our findings indicate BMI and vitamin D level, has a strong association with Blount's disease, which may be especially important among males. Further prospective research is needed to investigate the role of weight loss and treatment of vitamin D deficiency in the prevention of Blount's disease. ### 234 ASSESSMENT OF VENOUS ACCESS IN PEDIATRIC EMERGENCY CARE FACILITATED BY VEINLITE TECHNOLOGY WITH REDUCED PAIN AND TIME AND WITHOUT EXTENSIVE EXPERIENCE M. Chinn, C. Koerner *University of Texas at Houston, Houston, TX*. #### Purpose of Study Venous access in children can be difficult to achieve. Frey and Lininger demonstrated a 44% and 53% venous access success rate for RNs, respectively. Katsogridakis, et, al, showed statistical significance with transillumination (Veinlite) assisted venous access over standard access. The purpose of this pilot study is to determine whether Veinlite can facilitate venous access in children. #### Methods Used The study was conducted from June 9-13, 2008 (0700-1900), at a pediatric emergency center (0-21 years) serving an indigent population. All patients needing cannulation were eligible, except critical patients. Nurses were trained in the use of the Veinlite. Twenty-five envelopes were randomly assigned as Veinlite or Standard. The nurse chose an envelope and performed the indicated technique up to two times. Should the nurse fail at both attempts, another nurse continued the study. Patient data was obtained including body mass index (BMI), skin color, dehydration level, and prior cannulation history. Nurses provided information regarding cannulation experience and difficulty level of the procedure. #### Summary of Results Successful venous access on the first attempt was 83.33% with the transillumination versus 76.92% with the standard technique. Venous access was obtained in all patients within three attempts. There was no statistically significant difference between the two techniques in predicting successful venous access. #### Conclusions This study was limited due to the small sample size. Nurses with experience in cannulation showed no significant benefit with the use of the device. However, further studies should be done to determine the Veinlite's potential as an educational tool for inexperienced healthcare workers. Nurses expressed concerns with the learning curve needed to become fully proficient with the device, therefore a more rigorous training program should be investigated. View this table: [Table20](/content/57/1/301/T20) Data ### 235 ADOLESCENT PREVIOUSLY UNDIAGNOSED WITH ADVANCED AIDS PRESENTING TO THE EMERGENCY DEPARTMENT AS ODONTOPHAGIA J.W. Steele1, S. Stovall2, T.M. Thompson1,2 * 1UAMS, Little Rock, AR and 2UAMS/ACH, Little Rock, AR*. #### Case Report An 18 year old African American male presented to the emergency department at the state's only pediatric hospital with a chief complaint of "white stuff in my mouth and sore throat." Symptoms started six weeks prior and worsened over time. He had tried no medications nor sought medical attention prior to this ED visit, and had no longitudinal primary care. Further history revealed four weeks of subjective fevers and night sweats, several weeks of dry cough, and 1 day of abdominal pain with post-prandial vomiting. He also reported a 20-30 pound weight loss over the past 2 weeks. He had no past medical history, meds or allergies; was a senior in high school and smoked cigars/consumes alcohol socially. He admited to unprotected sexual intercourse with "a few" female partners and oral sex with at least 1 male partner. Physical exam revealed white plaques covering his tongue, tonsils, and the roof of this mouth, which were easily scraped off with a tongue blade. Exam was otherwise notable for anterior cervical/inguinal adenopathy and thin body habitus. Abdomen, lung, and cardiac exams were unremarkable. Initial lab work, revealed leukopenia; total WBC count of 3.8 with 23L and 60N. The remainder of the CBC, electrolytes, renal, liver function tests (including albumin and prealbumin) and strep screen were normal. He was admitted for further workup. Inpatient labs were positive for HIV ELISA/western blot with initial CD4 count of 17 cells per mm3. This adolescent was diagnosed with advanced AIDS with an opportunistic oral candidiasis. He improved on fluconazole, ART, and MAC/PCP prophylaxis and was discharged after receiving HIV education. Since diagnosis, he has received regular follow up in the infectious disease clinic, and his CD4 count has improved to 580. HIV is on the rise amongst adolescents nationally, and is often unrecognized until frank symptoms appear. This patient had been seen in our ED 10 months prior for posterior auricular cellulitis, but no oral exam was done nor social history obtained. Adolescents can fall through the cracks of our medical home system due to the lack of vaccine driven visits. This case emphasizes the importance of increased vigilance at every opportunity an adolescent presents for acute care. ### 236 CATCH-UP IMMUNIZATIONS AT 18 MONTHS OF AGE: IMPLICATIONS FOR INDIVIDUAL PRACTICES. A STUDY FROM THE SOUTH CAROLINA PEDIATRIC PRACTICE RESEARCH NETWORK (SCPPRN) J.T. McElligott1,2, E.S. O'Brien1, J.R. Roberts1, P.M. Darden1,2 * 1Medical University of South Carolina, Charleston, SC and 2Medical University of South Carolina, Charleston, SC*. #### Purpose of Study Analyses of the National Immunization Survey imply that an additional immunization visit at 18 months could have a substantial effect on immunization rates of individual children. What effect would one additional immunization visit at 18 months of age have on immunization rates of pediatric practices? #### Methods Used We completed retrospective chart reviews of 6 pediatric practices within the South Carolina Pediatric Practice Research Network (SCPPRN) on children aged 18 to 30 months of age. Up to date (UTD) status was defined as 4:3:1:3:3:1 (4 DTaP, 3 Polio, 1 Measles, 3 Hib, 3 Hepatitis B: 1 Varicella). Individual practice vaccination rates were determined at age 17 months, 18 months and at assessment. Of those not UTD at 17 months, the percentage of children who could be brought UTD with one visit was calculated for each practice. Calculations were performed with CoCASA 3.3.80. #### Summary of Results There were 2 rural, 2 urban and 2 suburban practices surveyed. The number of charts reviewed at each practice ranged from 117-616 (median 382). The vaccination rates for individual clinics were variable. UTD at 17 months ranged from 14%-58% (median 31.5%). For children not UTD, one additional visit would improve the range of practice vaccination rates to 41%-80% (median 63%). This represents an increase of 18%-51% (median 28.5%) for individual practices. The observed immunization rate at 18 months ranged from 23%-64% (median 37%) an increase of 3%-7% (median 5%) for those practices. #### Conclusions Practices are not effectively using an 18 month visit for catch up immunizations. Practice based interventions targeted at the 18 month health maintenance visit have the potential to substantially increase individual practice vaccination rates. ### 237 BLOOD CULTURES HAVE LITTLE UTILITY IN THE MANAGEMENT OF PEDIATRIC COMMUNITY-ACQUIRED PNEUMONIA V. Davis, S. Gupta, K. Monroe *University of Alabama-Birmingham, Birmingham, AL*. #### Purpose of Study Community-acquired pneumonia (CAP) is a frequent cause of hospitalization in children. The Joint Commission on Accreditation of Healthcare Organizations mandates obtaining two sets of blood cultures before treating hospitalized adult CAP patients in effort to identify the pathogens and narrow the spectrum of antibiotic coverage. Limited data exists on the clinical value of blood cultures in the management of hospitalized children with CAP. Despite no current guidelines for in-patient care of pediatric CAP, many pediatric practitioners routinely obtain blood cultures. The purpose of this study was to investigate the utility of blood cultures obtained at admission in the management of pediatric CAP. #### Methods Used This is a retrospective chart review of patients aged 3 months to 18 years with a discharge diagnosis of pneumonia who were admitted to the Children's Hospital in Birmingham, AL from 2004 to 2007. All data were analyzed using Microsoft Excel. Study protocol was reviewed and approved by the IRB at the University of Alabama-Birmingham. #### Summary of Results 985 cases were identified. Excluding for sickle cell (53), immunodeficiency including cancer and transplant (74), central venous access or home ventilator (15), hospitalized in the last 2 weeks (52), in-patient transfer (49), or incorrect diagnosis (22), there are 720 charts which have been analyzed. 519 (72%) of these patients had a blood culture obtained at admission. Of these patients, 58% were males, 42% were females, 36% were African American, 57% were white, and 6% were other races. The average age was 4.7 ± 4.4 years. The median length of stay was 3 days. Contaminates grew in 19 patients (3.7%) while pathogens grew in 14 cultures (2.7%). Ten of the cultures grew streptococcus pneumoniae, 1 staph aureus, 2 haemophilus influenza, and 1 klebsiella pneumoniae. Based on sensitivities, 8 of the 14 children could have had their antibiotic spectrum narrowed. However, in only two cases did culture results influence antibiotic selection. #### Conclusions Our data indicate that bacteremic pneumonia is rare and cultures are unlikely to influence therapeutic decision making. Blood cultures appear to have little utility in the management of children admitted to the hospital for CAP. ### 238 DOMESTIC VIOLENCE CURRICULUM IN RESIDENCY TRAINING-DOES IT CHANGE ATTITUDES AND SCREENING BEHAVIOR? S.B. Rizvi1, K. Franchek2, T. Duryea1 * 1Baylor College of Medicine, Houston, TX and 2University of Utah School of Medicine, Salt Lake City, UT*. #### Purpose of Study Children who witness domestic violence(DV)are at risk for long-term emotional/behavioral problems. The American Academy of Pediatrics issued guidelines on screening for and education about DV in residency training. Lack of training is identified as a significant barrier to physician screening. This study assessed the effectiveness of our resident training DV curriculum. #### Methods Used All Pediatric/Medicine-Pediatric interns at Baylor College of Medicine are required to attend a 4 hour training session at a local DV shelter. Knowledge, attitudes, and behaviors are surveyed prior to training and in the last six months of residency. Questions include how often residents screen during well visits, whether they had ever identified a DV victim, awareness of community resources/AAP guidelines, comfort level with screening, and attitude toward DV training and curriculum. #### Summary of Results To date, 25% (42/167, n = 42) of residents trained have completed both the pre- and post-training surveys. Pre and post answers were compared using Chi-square test for categorical variables and t-tests for continuous variables. All tests with a *P*-value of < 0.05 are considered significant. 14% of residents identified a victim prior to training compared with 57% at post-training. Results for screening during well child visits prior to and after training showed 33% vs. 19% reporting NEVER screening, 57% vs 64% reporting screening < half the time, 5% vs 12% reporting screening > half the time, and 5% vs. 5% reporting screening almost always. Awareness of AAP guidelines increased from 14% vs. 45% pre and post-training. Residents also reported increased awareness of DV resources post-training. There was a significant difference detected in residents reporting increased comfort levels screening for DV (*P* = 0.002) and a significant decrease in number of residents reporting training on DV was inadequate (*P* = 0.000). #### Conclusions Training on DV awareness and screening significantly increases resident comfort level with screening, satisfaction with training, and tends to increase screening behavior and identification of victims. Differences in screening behavior may also be affected by other clinical experiences. Future studies are ongoing to evaluate this. ### 239 SUBACUTE BACK PAIN IN AN ADOLESCENT CAUSED BY *EIKENELLA CORRODENS* VERTEBRAL OSTEOMYELITIS: A CASE REPORT S. Chhabra, R.E. McCarthy, N.S. Harik *University of Arkansas for Medical Sciences, Little Rock, AR*. #### Purpose of Study *Eikenella corrodens* is a small, fastidious, capnophilic, anaerobic gram-negative rod found in gingival and bowel flora of approximately 40-70% of people. It is most often implicated in infections secondary to human bites. *E. corrodens* also causes endocarditis, head and neck infections, and periodontitis. There have been multiple case reports of osteomyelitis caused by *E. corrodens*, several involving penetrating injury and subsequent contamination with oral flora. However, few cases of *E. corrodens* have been in children, and only one has been vertebral osteomyelitis or diskitis. #### Methods Used Literature review #### Summary of Results A healthy 17-year-old girl presented to our hospital with worsening of subacute back pain of 2 months duration. There was no history of trauma, fever, or sudden onset of symptoms. MRI of the spine and Bone Scan suggested vertebral osteomyelitis. Inflammatory markers were not significantly elevated {ESR 30 (nl 0-20), CRP <3 (nl 0-10)}. She was treated with clindamycin and subsequently switched to vancomycin secondary to lack of clinical improvement. With the hope of establishing a definitive diagnosis, an open biopsy was done. Pathology revealed acute and chronic inflammation and granulation tissue formation consistent with osteomyelitis and associated diskitis. Gram stain of bone tissue revealed tiny gram negative rods and cultures grew *E. corrodens* after which ampicillin was started. She completed 8 weeks of IV ampicillin and required extensive physical therapy. She had a slow recovery unrelated to continued infection, but rather to physical injury. #### Conclusions The first and only reported case of *E. corrodens* infective diskitis in the pediatric population was also in an adolescent without any evidence of trauma and a prolonged history of back pain. Vertebral osteomyelitis and diskitis in the pediatric population is mostly seen in younger children and common implicated pathogens are *S. aureus, Streptococci, H. influenzae*, and *Enterobacter* species. Consideration must be taken to include *E. corrodens* as a possible pathogen for this type of infection, especially in adolescents with a less acute course. It should also be considered in patients without clinical improvement on conventional antibiotic therapy as *E. corrodens* is resistant to clindamycin. ## **Allergy, Immunology, and Rheumatology Concurrent Session** 2: PM Friday, February 13, 2009 ### 240 ANTI-HUMAN DEATH RECEPTOR 5 INDUCED APOPTOSIS IN MOUSE CELL LINES BY A NOVEL HUMAN-MOUSE CHIMERIC MOLECULE J. Li1, P. Yang1, H. Hsu1, J. Mountz1,2 * 1University of Alabama at Birmingham, Birmingham, AL and 2VA Medical Center, Birmingham, AL*. #### Purpose of Study Death receptor 5 (DR5) is a pro-apoptotic protein considered as a key target for cancer therapy. An anti-human DR5 agonistic antibody, TRA-8, has been shown to induce apoptosis in various tumor cells and thus is regarded as one of the most promising therapeutic strategies. However, a mouse model that can be used to evaluate the TRA-8 therapeutic response is lacking. The purpose of this study is to generate a humanized mouse DR5 molecule that can be used to determine the mechanism of DR5 mediated apoptosis in a mouse using a therapeutic anti-human DR5 antibody. #### Methods Used A 1kb and a 3kb putative promoters, and a 3 kb first intron of mouse DR5 were subcloned upstream of a chimeric DR5 consisting of a human extracellular domain, a mouse transmembrane and an mouse intracellular domain. This enabled analysis of DR5 function in mouse cells with TRA-8. Transfection was performed by using Lipofectamine and nucleofection. Chimeric DR5 expression was determined by FACS and Western blot. Cell death was estimated by the ATPLite. #### Summary of Results The human/mouse (hu/mo) DR5 chimeric protein was successfully transported and targeted to the mouse cell membrane. Maximal expression was seen with the 1 kb promoter in NIH3T3 and 4T1 cells. Combination of longer promoter with first intron conferred authentic expression of chimeric DR5. Mouse promoter exhibited limited activity in human HEK293 cells. High expression of hu/mo DR5 resulted in high cell death in NIH 3T3 and 4T1 cells with less apoptosis in the anti-DR5 resistant L5178 cell. Human full-length DR5 induced low apoptosis in mouse cells. Crosslinking of the hu/mo DR5 with TRA-8 enhanced apoptosis with efficacy varying from 20% (shorter promoter, high DR5 expression) to 60% (longer promoter plus the first intron, authentic DR5 expression). #### Conclusions We generated and optimized a hu/mo DR5 molecule with essential regulatory elements that can enable authentic expression of DR5 and the induction of apoptosis by TRA-8 in mouse cells. This construct will lead to the generation of a novel transgenic mouse for analysis of the anti-human DR5 apoptosis mechanism, therapeutic response and DR5 expression regulation in both cancer and autoimmune diseases. ### 241 ASSESSMENT OF MECHANISMS BY WHICH APL-A12 SUPPRESSES ARTHRITIS WHEN ADMINISTERED ORALLY S.E. Hammond, D.L. Cullins, A.H. Kang, A.E. Postlethwaite *University of Tennessee, Memphis, TN*. #### Purpose of Study There is compelling evidence that the inflammatory process in rheumatoid arthritis (RA) is in part driven by an autoimmunity to Type II collagen (CII). DR1 transgenic (tg) mice immunized with CII develop a polyarthritis similar to RA. The purpose of our study was to determine the mechanism by which the altered peptide ligand of CII263-270, termed A12, suppresses arthritis when given orally to DR1 mice. #### Methods Used To this end, DR1 tg mice and DR1 TCR double tg mice were fed 8-9 doses of 50 μg/1000 μl A12, with controls fed A2 or PBS. DR1 tg mice were subsequently immunized with a CII:CFA emulsion. Mice were sacrificed, and spleen and various lymphoid tissues were removed. Cell populations were cultured with A2, A12, or PBS, and then analyzed for cytokines and cell surface markers. #### Summary of Results Flow cytometry data showed splenocytes from mice fed A12 secreted IL-4 but not IL-17. Cells were activated and upregulated CD69. CD25 and FoxP3 were seen in mice fed A2 but not A12. An IFNγ assay showed A12 remarkably decreased IFNγ levels from controls. However, A12 does not induce Treg cells. #### Conclusions These data show a down regulation of TH1 cytokines and upregulation of TH2 cytokines in mice gavaged with A12, establishing A12 as a potent suppressor of collagen-induced arthritis. Interestingly, A12 seems to induce an inhibitory T cell, the elucidation of which might lead to an effective and specific therapy for rheumatoid arthritis. ### 242 PREDICTORS OF RESPONSE TO ANTI-TNF-α THERAPIES IN TWO UNIVERSITY POPULATIONS WITH RHEUMATOID ARTHRITIS R.S. Daniel1, R. Bourne2, A.N. Simpson1, K.S. O'Rourke2, M.B. Bolster1 * 1MUSC, Charleston, SC and 2WFUBMC, Winston-Salem, NC*. #### Purpose of Study To determine predictors of anti-tumor necrosis factor alpha (antiTNF) therapy in rheumatoid arthritis (RA). #### Methods Used Medical records of patients with RA were reviewed. Adult subjects with >1 autoimmune disease were excluded (except secondary Sjogren). Subjects were assigned a group: Responder, Switcher, or Failure. The Responder group included subjects who remained on the initial antiTNF medication for >90 days. The Failure group included subjects who were no longer on an antiTNF medication regardless of reason for discontinuation and duration of therapy. The Switch group contained subjects who were exposed to >1 antiTNF medication and continued on an antiTNF agent for >90 days, otherwise they were considered Failures. To control for antiTNFα selection bias we constructed a propensity score categorical variable and performed a logistic regression. #### Summary of Results Of the 1313 records reviewed there were 110 Responders, 48 Switchers, and 21 Failures. 64 patients received adalimumab (ADA) as their initial antiTNF therapy with 83% (53) not switching or stopping ADA. Of the patients who initially received infliximab (INF) or etanercept (ENT), 52% (27/52) and 51% (32/63) did not switch or discontinue the drug, respectively. Patients taking MTX with an ESR >50 mm/hr had an increased likelihood of antiTNF therapy failure [OR 23.6 (*P* = 0.0144)]. Patients with thyroid dysfunction or osteoporosis, regardless of MTX use and ESR value at baseline, had a 3.9-fold higher risk of failing antiTNF therapy (*P* = 0.0363). Patients prescribed ADA first had the lowest likelihood of switching therapy [OR 0.293(0.117, 0.734) *P* = 0.0088], while ENT had the greatest likelihood of switching [OR 2.51(1.129, 5.580) *P* = 0.0240] regardless of MTX dose. Patients on MTX <15 mg weekly were 2.8 fold more likely to switch to a second antiTNF therapy (*P* = 0.0194), than patients on MTX >15 mg weekly at baseline. #### Conclusions MTX dose should be titrated to at least 15 mg weekly and attempts should be made to lower ESR prior to antiTNF therapy to minimize the likelihood of antiTNF discontinuation. Patients prescribed ADA first had the lowest likelihood of switching therapy, while etanercept had the greatest likelihood of switching regardless of MTX dose. ### 243 IN VITRO IMMUNOMODULATORY EFFECTS OF STRESS HORMONES ON GENE EXPRESSION OF CYTOKINES AND COSTIMULATORY MOLECULES IN HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS L. Xiang, G.D. Marshall *University of Mississippi Medical Center, Jackson, MS*. #### Purpose of Study Stressors can influence immune function through various mechanisms including impact on various regulatory elements. Stress hormones, glucocorticoids (GC) and catecholamines (CT), altered T helper 1 (Th1)/Th2 cytokine production and its balance. These immunoregulatory imbalances are associated with serum cortisol levels and can be reproduced in the presence of GC in vitro. This study focused on the mechanisms of immunomodulatory effects of stress hormones on human peripheral blood mononuclear cells (PBMC). #### Methods Used PBMC from 16 healthy adults were stimulated for 11 days with or without 10-8M DEX or EPI looking for changes (at 24hr and 11days) in (a) gene expressions of cytokines (IFNγ, IL-4, IL-10) and costimulatory molecules including CTLA-4, CD28, CD80, and CD86 by real time RT-PCR, (b) Th1/Th2 cytokines (IFNγ, IL-4) by ELISA (pg/ml), and (c) regulatory T cell populations (Treg - CD4 + CD25 + FoxP3+) by flow cytometry (% of total CD4+). #### Summary of Results The results showed that, in 24 hour (short term) incubation with DEX Treg were significantly decreased (1.4 vs. 1.8 control, *P* < 0.001) and both IFNγ production and mRNA were inhibited (*P* < 0.001 and *P* < 0.01, respectively), IL-10 mRNA was more than 2-fold increased compared to control group (*P* < 0.001), and costimulatory molecules CD28 and CD80 mRNAs were decreased as well (*P* < 0.001 and *P* < 0.01, respectively). However, Th1/Th2 cytokine balance was unaffected by DEX. After 11 day (long term) incubation with DEX, Th1/Th2 ratio was significantly decreased (26.2 vs. 42.9 control (*P* < 0.05) indicating a change to Th2 cytokine dominance. Additionally CTLA-4 (a late regulatory costimulatory factor) mRNA was decreased (*P* < 0.05). #### Conclusions Although GC can affect immunomodulation in early stage through suppressing Treg and a decrease in Th1 cytokine, induction of a Th2 shift occurred later, after 11 day incubation. Additionally CD28/CD80-86 costimulatory signal pathway may be a target of stress hormone in acute stress duration whereas CTLA-4/CD80-86 pathway may be more affected by chronic stress. This study provides additional understanding of the bidirectional communication between neuroendocrine and immune systems that are characteristic of individuals experiencing high levels of psychological stress. ### 244 SENSITIVITY AND SPECIFICITY OF DIAGNOSTIC CRITERIA FOR ATROPHIC RHINOSINUSITIS T. Ly1, R. deShazo1, J. Olivier1, S. Stringer2, C. Stodard3 * 1University of Mississippi Health Care, Jackson, MS; 2University of Mississippi Health Care, Jackson, MS and 3University of Mississippi Health Care, Jackson, MS*. #### Purpose of Study Atrophic rhinosinusitis (AtR) is a clinical syndrome associated with progressive loss of normal ciliated nasal epithelium, resulting in persistent mucociliary dysfunction and intractable nasal symptoms. Since there were no diagnostic criteria available for diagnosis or to perform multicenter trials for this disease, we proposed six diagnostic criteria for AtR (recurrent epistaxis, episodic anosmia, recurrent nasal purulence, nasal crusting, chronic inflammatory disease of the upper airway and two or more sinus surgeries), and found these to be sensitive and specific for the diagnosis when used together. In this investigation, we sought to determine if fewer than the six criteria were sensitive and specific for the diagnosis of AtR. #### Methods Used We identified 22 patients for whom there was a consensus on the diagnosis of AtR among a team of faculty allergist-immunologists and otolaryngologists, and compared these patients to 22 randomly selected patients with chronic rhinosinusitis. The medical records of the 22 study subjects and 22 control patients were reviewed. Clinical data on patients were analyzed using a commercial software program (SAS version 9.1; SAS Institute, Inc.; Cary, NC). #### Summary of Results The risk for of AtR as compared to controls was increased (1) 25-fold for recurrent nasal purulence (95% confidence interval [CI], 2.9-221.7), (2) 12-fold for recurrent epistaxis (95% CI, 1.3-106.8), (3) 15-fold for two or more sinus surgeries (95% CI, 3.5-66.7), and (4) 7-fold for anosmia (95% CI, 0.9-72.1). All 6 criteria were more common in the AtR group than the control group (*P* ≤ 0.05). All (100%) patients in the study group had 2 or more of those 6 criteria as compared to 36% from the control group. An increasing number of criteria were associated with an increasing probability of AtR by logistic regression analysis (OR: 5.9; 95% CI: 2.2-15.4; *P* < 0.001). Any two of the 6 criteria yielded a sensitivity of 0.95 and specificity of 0.77 for the diagnosis. #### Conclusions Patients with chronic rhinosinusitis who meet any 2 of the 6 proposed diagnostic criteria for AR can be diagnosed with AtR with a high level of sensitivity and specificity. ### 245 FOOD DEPENDANT EXERCISE INDUCED ANAPHYLAXIS TO WHEAT MAY BE DIAGNOSED USING WHEAT FLOUR S.W. Oberhoff, J. El-dahr *Tulane University Medical School, New Orleans, LA*. #### Purpose of Study Patients with suspected Food Dependant Exercise Induced Anaphylaxis (FDEIA) often are negative to foods when tested by CAP-RAST or commercial food extracts, but may react to heat-labile food antigens. Heat-labile antigens in wheat, have been implicated as a common allergen in FDEIA but no practical test is currently available. #### Methods Used Skin testing was performed on three adolescents with a common history of anaphylaxis after eating products suspected to contain raw or partially cooked wheat flour and exercising shortly thereafter. Both standard commercial food extracts and a wheat flour slurry were used in addition to positive and negative controls. #### Summary of Results In all three cases the patients were negative when tested to commercial food extracts but were markedly positive when prick to prick was performed with raw wheat flour. Non-specific reactivity to wheat flour was not present when done on normal volunteers. #### Conclusions Skin testing with standard commercial wheat extracts for patients with Food Dependant Exercise Induced Anaphylaxis may not be sufficient in determining whether wheat products are the responsible trigger. Prick-to-prick skin testing using wheat flour is an easy and practical way for clinicians to determine which patients should avoid wheat prior to exercise to prevent further episodes. ### 246 COMPLEMENT DEFICIENCY IN A LARGE COHORT OF FAMILIAL SYSTEMIC ERYTHEMATOSUS R. Aggarwal1, A. L. Sestak2, B. Namjou2, H. Scofield1,2 * 1OUHSC, OKC, OK and 2OMRF, OKC, OK*. #### Purpose of Study Systemic lupus erythematosus is common among subjects with hereditary deficiency of early complement components such as C1, C2 or C4. For example, up to 75% of those with complete C4 deficiency have SLE, while about 10% of cohorts of subjects with C2 deficiency have the disease. The concordance rate for SLE among siblings with complement deficiencies is greater than 90%. We undertook the present study to determine the prevalence of hereditary complement deficiency in familial SLE. #### Methods Used We have identified and collected families in which two or more individuals have SLE. Patient interview and questionnaire along with medical record review confirmed that all SLE patients met at least 4 ACR classification criteria. Each subject underwent CH50 testing. Medical records were reviewed for selected subjects in regards to complement measurements. #### Summary of Results A total of 538 families with two or more SLE patients were studied among which there were 1135 individuals who met criteria for SLE. There 66 SLE affected subjects with a zero CH50 value, and 62 of the 66 had an SLE-affected family member with a non-zero CH50 value. These 62 families, where one SLE affected subject had a CH50 of zero while other SLE affected members had non-zero CH50 values, were assumed to not have hereditary complement deficiency. Thus, there were two sets of SLE-affected siblings (i.e., two families) in which all the SLE patients had zero values for CH50, indicating the possibility of a hereditary complement deficiency. Examination of the medical records from these families showed that both SLE patients in one of the families and one SLE patient in the second family had normal serum C3 and C4 values. Thus, these two families may have C2 deficiency or a C1 component deficiency. #### Conclusions SLE is common when cohorts of complement deficient families or individuals are studied. In contrast, we have studied a large number of families with 2 or more SLE patients. Among this cohort, complement deficiency is not common, tentatively occurring in only 0.35% of families. Thus, while potentially highly informative as to pathogenesis, complement deficiency not does contribute significant numbers to familial SLE. ### 247 SYSTEMATIC REVIEW AND META-ANALYSIS OF IMMUNOSUPPRESSANT THERAPY CLINICAL TRIALS IN MEMBRANOUS LUPUS NEPHRITIS J. Swan, V. Majithia, D. Riche, K. Riche *University of Mississippi Health Care, Jackson, MS* #### Purpose of Study There is no current consensus for the standard of care treatment of patients with Class V membranous lupus nephritis. Amongst trials, there is inconsistency concerning the length of follow-up, different outcome measures, and no control group. The improbability of large, controlled trials for membranous lupus nephritis makes a meta-analysis of currently available data critical to gain clinically relevant insight for comparing immunosuppressant therapies. #### Methods Used Studies were identified by searching PubMed and OVID databases for human clinical trials using the key phrases: "membranous lupus nephritis" and "membranous lupus glomerulonephritis." Trials were included which contained data specific to Class V pure membranous lupus nephritis. The primary endpoint was complete, partial, and no response rate. The primary analysis evaluates any treatment, while the subgroup analysis isolates mycophenolate mofetil (MMF). A proportion meta-analysis using a DerSimonian-Laird random-effects model was performed. Data are reported as proportions with 95% confidence intervals (95% CI). #### Summary of Results Seven studies (n = 124) were included in primary analysis, while 4 studies (n = 56) were evaluated in the MMF subgroup. In patients receiving any treatment, there was a significantly higher proportion of complete response (0.59; 95% CI 0.40 to 0.77) and partial response (0.39; 95% CI 0.23 to 0.57) than non-responders (0.07; 95% CI 0.02 to 0.14). In the MMF subgroup, there was a more profound increase in complete response rate (0.65; 95% CI 0.26 to 0.94) and partial response rate (0.47; 95% CI 0.19 to 0.76) as compared to non-responders (0.02; 95% CI 0.00 to 0.06). Though bias was not present in either analysis (Egger, *P* > 0.1), statistical heterogeneity was significant in all primary analysis groups (*P* < 0.1 for all). #### Conclusions Based on the overwhelming positive evidence in this analysis and lack of current and improbability of future large, controlled trials, we recommend that treatment be considered in all patients with Class V membranous lupus nephritis with or without the presence of other classes. The subgroup analysis also strongly supports use of mycophenolate mofetil (MMF) should be considered the drug of choice as there is a significant positive response and extremely low non-responder rate. ### 248 ROLE OF REACTIVE INTERMEDIATES IN LUPUS NEPHRITIS A.K. Mashmoushi1, A.F. Hofbauer1,2, P. Komlosi1, P.D. Bell1, J. C. Oates1,2 * 1Medical University of South Carolina, Charleston, SC and 2Ralph H. Johnson VA Medical Center, Charleston, SC*. #### Purpose of Study Pharmacological inhibition of inducible nitric oxide synthase (iNOS) in murine lupus nephritis (LN) decreased disease activity and markers of reactive nitrogen and oxygen intermediates (RNI and ROI), yet genetic modulation of iNOS had little effect on murine LN. These results suggest that additional enzyme targets for NOS inhibitors may be important for disease progression. Little is known about enzyme source and cellular origin of reactive intermediates (RIs) in LN glomeruli. Il-6 is associated with proliferative LN. The purpose of this study is to determine the cellular origin of iNOS-mediated RI production in LN glomeruli and the role of RI in mesangial cell IL6 production. #### Methods Used Glomeruli were isolated from 3 groups of mice at 16 weeks of age: MRL-MpJ*FAS* lpr(MRL/lpr) mice either lacking functional NOS2 gene or with a functional NOS2 gene and MRL/MPJ controls. Glomeruli were then examined by 3-color confocal microscopy after staining with fluorescent probes for NO(DAF-FM DA) and reactive oxygen (RO)(CM-H2DCF-DA). Immortalized MRL/lpr mesangial cells were stimulated with LPS(100ng/ml)/IFγ(10U/ml) in the presence of increasing concentrations of S-nitroso-N-acetylpenicillamine (SNAP 50,100,250,500 uM). After overnight culture, supernatants were analyzed for IL6 by ELISA. #### Summary of Results Levels of fluorescence indicating NO and ROIs production were greatest in glomeruli from wt mice, and significantly lower levels were observed in NOS2 knockout and control glomeruli. Fluorescence intensity in wt glomeruli was localized to the capillary loops region. Stimulated mesangial cell IL6 production was inhibited more by low (50 mM) than high (500 mM) concentrations of the SNAP(see table) #### Conclusions Glomerular iNOS activity is a major source of RI production in this model of murine LN. Podocytes and/or endothelial cells appear to be a source of RI produciton rather than mesangial cells in murine LN. Given that lower concentrations of NO had a greater effect on IL6 production, paracrine NO production may act through multiple mechanisms to modify IL6 production in mesangial cells. View this table: [Table21](/content/57/1/301/T21) Effect of NO donor (SNAP) on IL6 production in MRL/lpr mesangial cells stmulated with LPS/IFγ ### 249 BIOMARKERS OF ATHEROSCLEROSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS R.L. Ravenell1, S. Shaftman2, M. Cappuccio4, T. Fleury1, J. Dononhue1, H. Zhu1, D. Spence3, T. Parker1, L. Ueberroth1, J. Oates1 * 1Medical University of South Carolina, Charleston, SC; 2Medical University of South Carolina, Charleston, SC; 3Robarts Research Stroke Prevention and Atherosclerosis Research Centre, London, ON, Canada and 4Medical University of South Carolina, Charleston, SC*. #### Purpose of Study To describe the relationship between serum biomarkers of reactive intermediate production and the extent of atherosclerosis in patients with systemic lupus erythematosus (SLE) with the ultimate goal of developing a cardiovascular risk factor model for patients with lupus. #### Methods Used 30 subjects were enrolled between the ages of 18 and 80 and met at least four of the 1997 revised ACR SLE criteria but without a history of stroke, myocardial infarction, cardiac bypass or stenting. Personal cardiac history and Framingham risk factors were reviewed, including family history of cardiovascular disease and SLE disease activity and damage. Sera collected were analyzed for cholesterol, lupus activity markers, and biomarkers of systemic reactive intermediate production- serum 3-nitrotyrosine(3NTyr), ortho-Tyr, meta-Tyr and 3-chloroTyr by high performance liquid chromatography. Urine 8-isoprostane F2 levels were measured by immunoaffinity extraction-gas chromatography-negative ion chemical ionization-mass spectrometric detection. Carotid ultrasound measurements were performed to determine plaque area in both carotids. Descriptive analysis was performed on all variables. SPSS was used to investigate the relationship of the biomarkers with plaque area and traditional risk factors using Pearson correlation for continuous variables and chi-square test for group variables. P values <0.05 were significant. #### Summary of Results Correlation was noted between the following: age and total plaque (*P* = 0.020), waist-hip ratio and LDL/HDL ratio (*P* = 0.034) and LDL and ortho-tyrosine (*P* = 0.031). A trend was also noted in total plaque and 3-nitrotyrosine levels. #### Conclusions These data suggest a relationship between the variables of age, possibly nitro-tyrosine and plaque as well as between LDL/HDL ratio and ortho-tyrosine. Our study is powered for 100 patients, and continued enrollment and anlaysis should be performed to determine if a predictive model using markers of reactive intermediate production can be developed that is more predictive than standard disease risk factors. ### 250 CLINICAL CHARACTERISTICS OF SARCOID RHINOSINUSITIS J.S. Reed, R. deShazo *University of Mississippi, Jackson, MS*. #### Purpose of Study We sought to better understand the demographics and clinical features of sarcoid rhinosinusitis (SRS) in patients identified using 3 established diagnostic criteria. #### Methods Used Using multiple search engines, we searched the medical literature from ten years prior to our original publication in 1999 to the present using the MeSh terms: nasal sarcoidosis and sarcoid of the sinuses. All charts of patients from our clinic with the diagnosis of sarcoidosis were pulled for review. Chart and case report data were reviewed using diagnostic criteria (chronic rhinosinusitis, a biopsy showing noncaseating granuloma, and appropriate ancillary testing to exclude other granulomatous conditions of the respiratory tract) to select patients with sarcoid rhinosinusitis for this study. Research was approved by our IRB. #### Summary of Results Our literature search identified 53 case reports, 20 patients from which met the diagnostic criteria. The clinical features of 9 patients with SRS we reported in 1999, 10 new patients identified in our clinic and the 20 reports in the literature were compiled to better understand the demographics and clinical features of this disease. The majority of the 39 patients were African-American(66%) females (77%). Nasal obstruction was the most common presenting complaint (74%) but nasal crusting (49%), anosmia (46%), headache (21%), and facial pain (18%) were also common. The majority of patients (72%) had pulmonary sarcoidosis (72%) or other forms of extra pulmonary sarcoidosis (79%) at the time of presentation. Of 30 patients where treatment data were available, all had received oral corticosteroids and 80% had received other immunosuppressive therapy, primarily methotrexate. #### Conclusions Sarcoidosis of the upper respiratory tract should be considered in patients with chronic rhinosinusitis, persistent nasal crusting, or anosmia even in the absence of an established diagnosis of sarcoidosis. The disease appears to require long term treatment. Since this population is especially prone to steroid side effects, early use of steroid sparing agents should be considered. ## **Cardiovascular I Concurrent Session** 2:00 PM Friday, February 13, 2009 ### 251 RECOVERY FROM MUSCLE WASTING AND PREVENTION OF PROGRESSIVE CARDIAC FIBROSIS IN RATS WITH ALDOSTERONISM TREATED WITH EPLERENONE K.D. Green, M S. Gandhi, Y. Sun, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN* #### Purpose of Study Chronic renin-angiotensin-aldosterone system (RAAS) activation is accompanied by a systemic illness that includes a progressive wasting of soft tissues, together with an adverse structural remodeling of myocardium. To address pathophysiologic responses involved, we employ 8-wk model of aldosterone/salt treatment (ALDOST) in young adult male rats, where a failure to gain weight and progressive atrophy of skeletal muscle is found, together with a progressive fibrosis of myocardium. We hypothesized the wasting and adverse cardiac remodeling seen with ALDOST could respectively be reversed and halted by eplerenone (Epler), an ALDO receptor antagonist, introduced at wk 4 of ALDOST. #### Methods Used Eight-week-old Sprague-Dawley rats received ALDO (0.75 μg/h by implanted minipump) for 8 wks, together with 1% NaCl/0.4% KCl in drinking water. A subgroup was given Epler (100 mg/kg/day in divided doses by twice daily gavage) starting at wk 4 and continued to wk 8. Untreated, age-/gender-matched rats served as controls. We monitored body and skeletal muscle (gastrocnemius) weight. The presence of cardiac fibrosis in right and left ventricles was assessed by light microscopy and picrosirius red staining of fibrillar collagen and quantitated as collagen volume fraction (CVF, %). #### Summary of Results Body weight at 8 wks ALDOST was less (*P* < 0.05) than untreated controls (250 ± 17 vs. 370 ± 8 g) and this wasting could be largely recovered (*P* < 0.05 vs. ALDOST) by Epler cotreatment (330 ± 8 g). Muscle weight was reduced (*P* < 0.05) at 8 wks ALDOST compared to controls (0.53 ± 0.02 vs. 0.74 ± 0.01 g) and could be recovered (0.73 ± 0.02 g) with Epler cotreatment. Compared to controls, CVF was increased (*P* < 0.05) at 4 wks ALDOST (9.0 ± 0.5% vs. 3.5 ± 0.4%) and this fibrosis continued to accumulate (*P* < 0.05) at 8 wks ALDOST (11.5 ± 0.6%). This progressive fibrosis was prevented (*P* < 0.05 vs. ALDOST) by Epler cotreatment (9.7 ± 0.7%). #### Conclusions Thus, a failure to gain weight and wasting of skeletal muscle accompanies chronic ALDOST and could be largely reversed by Epler cotreatment, which also halted the progressive cardiac fibrosis. A recovery of wasting requires a reversal of aldosteronism. ### 252 CHRONIC LEFT-VENTRICULAR DYSFUNCTION INCREASES OXIDATIVE STRESS IN SKELETAL MUSCLE: POTENTIAL MECHANISM OF CACHEXIA IN CONGESTIVE HEART FAILURE L. Semprun-Prieto1,2, S. Sukhanov1, J. Bhutto1, J. Titterington1, P. Delafontaine1 * 1Tulane University, New Orleans, LA and 2Tulane University, New Orleans, LA*. #### Purpose of Study Congestive heart failure (CHF) affects more than 5 million Americans and is associated with progressive skeletal muscle atrophy, which is a predictor of reduced survival. Increasing evidence implicates oxidative stress in the pathophysiology of cardiovascular disease, but its involvement in CHF induced skeletal muscle wasting is unknown. To address mechanisms of skeletal muscle atrophy and the potential role of oxidative stress, we used a murine model of chronic left-ventricular dysfunction (CLVD) #### Methods Used Myocardial infarction was induced by ligation of the left coronary artery (LAD, n = 7) in 8 to 12 week old FVB mice, and the control group underwent the same surgery without ligation (ctr, n = 12). CLVD was assessed by echocardiography. Oxidative stress was quantified by staining skeletal muscle cross-sections with superoxide-sensitive dye dihydroethidium after subtraction of background. #### Summary of Results LAD-ligated animals had significant left-ventricular dysfunction as determined by echocardiography at 12 weeks. (% FS, ctr, 47.24 ± 4.4% vs. LAD, 28.6 ± 4.7%; *P* < 0.05, LVDs, ctr, 4.4 ± 0.4mm vs. LAD, 3.6 ± 0.1mm, *P* < 0.0001; LVDd, control 1.9 ± 0.1mm vs. LAD, 3.1 ± 0.5mm, *P* < 0.0001). In addition, LAD ligation produced significant skeletal muscle atrophy as evidenced by a decrease in body weight (ctr, 29.61 ± 0.37g vs. LAD, 27.76 ± 0.68g, *P* < 0.05), decrease in skeletal (gastrocnemius, GM) muscle weight (ctr, 133.9 ± 2.2mg vs. LAD, 126.3 ± 1.7mg, *P* < 0.05), reduction in GM fiber cross-sectional area (control 1292.2 ± 70.1 μm2, n = 5, vs. LAD, 934.1 ± 10.7 μm2, n = 2, *P* < 0.05), assessed by analysis of H&E-stained cross-sections and a significant change in the myofiber size distribution with an increased number of smaller size fibers (frequency distribution analysis, *P* < 0.0001). CLVD-induced muscle wasting was associated with a 51% increase in muscle superoxide levels (relative DHE fluorescence, ctr, 18.20 ± 2.9 vs. LAD, 27.40 ± 5.4). #### Conclusions In summary, CLVD produces an increase in skeletal muscle superoxide levels concomitant with progressive muscle atrophy. These findings provide insights into mechanisms of cachexia development in CHF and offer potentially new therapeutic strategies. ### 253 CARDIOMYOCYTE EXPRESSION OF METAL RESPONSE ELEMENT TRANSCRIPTION FACTOR-1, METALLOTHIONEIN-1 AND ZINC TRANSPORTERS IN RATS WITH ALDOSTERONISM. RESPONSE TO SPIRONOLACTONE OR AMLODIPINE P.A. Deshmukh, G. Kamalov, N. Baburyan, R.A. Ahokas, Y. Sun, S.K. Bhattacharya, I.C. Gerling, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN*. #### Purpose of Study An excessive accumulation of cardiomyocyte intracellular [Ca2+]i occurs with aldosterone/salt treatment (A) and is accompanied by [Zn2+]i loading. Cardiomyocyte Zn entry involves L-type Ca2+ channels (LTCC) and Zn transporters with increased cytosolic free [Zn2+]i activating its sensor, metal response element transcription factor (MTF)-1, which upregulates the transcription of a Zn importer (Zip1) and exporter (ZnT-1) and a Zn-binding protein metallothionein (MT)-1. #### Methods Used Cardiomyocytes were harvested by collagenase perfusion and [Zn2+]i monitored by flow cytometry using Fluozin-3 and total Zn2+ by atomic absorption spectrophotometry. Total mRNA and protein obtained from cardiomyocytes and quantitative real-time PCR used to assess mRNA expression of MTF-1, MT-1, Zip1 and ZnT-1. Their expression, relative to control cells, was calculated using the delta-delta Ct method. Expression of MTF-1 protein was determined by immunoblotting. Four groups were studied: age-/gender-matched controls (C); A alone (0.75 μg/h by minipump + 1% NaCl/0.4% KCL in drinking water); A + spironolactone (S) (150 mg/kg/day by gavage); and A + amlodipine (CCB; 5 mg/kg/day by gavage). #### Summary of Results *P* < 0.05: *A vs. C, †A + S vs. A, ‡A + CCB vs. A #### Conclusions Total Zn2+ and [Zn2+]i were increased during A and involved Zn entry via LTCC and Zip1 importer. [Zn2+]i activates MTF-1 and expression of MT-1 and Zip1, and ZnT-1 exporter to prevent cytotoxicity. Cotreatment with S prevented the rise in [Zn2+]i and expression of MTF-1 encoded genes while CCB attenuated these responses View this table: [Table22](/content/57/1/301/T22) ### 254 NECESSITY OF HOLTER MONITORING IN PACED PEDIATRIC PATIENTS A. Bitar1, S. Helmig1, C.S. Snyder2 * 1Tulane University School Of Medicine, New Orleans, LA and 2Ochsner Clinic Foundation, New Orleans, LA*. #### Purpose of Study Close follow-up of pediatric pacemakers is important to the longevity of these devices. Holter monitors may ascertain issues not detected during routine interrogation. The purpose of this study is to determine if Holter monitoring is a useful adjuvant to analyze pacemakers in the pediatric population. #### Methods Used An IRB approved, retrospective review, of the pediatric cardiology database was performed to identify all paced patients. Inclusion criteria included: age <18 years, pacemaker, Holter monitor, and results of interventions. Data collected included pacemaker interrogation and Holter monitor results. Holter results were listed as either normal or abnormal. Holter abnormalities were placed into two groups: major, requiring interventions and minor, requiring close follow up. #### Summary of Results We identified 90 patients with 182 Holters (range 1-5) average 2 per patient. We identified 160 (88%) normal and 22 (12%) abnormal Holters. Abnormalities were detected on the first Holter in 72% and on second and third Holter in 13% each. Of the 22 abnormal Holters, there were 10 major abnormalities and 12 minor ones. Major abnormalities were: atrial undersensing (4), SVT (3), inappropriate ventricular sensing (3), inappropriate atrial sensing (1), and pacemaker mediated tachycardia (1). Interventions included changing atrial sensitivity/polarity, cardioversion, and medications. Minor abnormalities included rare atrial undersensing (4), previously unknown PVCs (3), inappropriate Holter quality (1), and rare episodes of bradycardia (1). None of these minor abnormalities were detected on follow up Holter monitors. #### Conclusions Holter monitoring in paced pediatric patients revealed previously unidentified abnormalities in almost 12% of Holters. Major abnormalities requiring interventions were found in 54.5% of abnormal Holters. We believe that Holter monitoring of paced pediatric patients can detect previously unknown abnormalities. ### 255 LYMPHOCYTOPENIA IN AFRICAN-AMERICANS WITH DECOMPENSATED HEART FAILURE. ROLE OF SPLANCHNIC CONGESTION S. Ali, A.U. Shahbaz, M.D. Nelson, A. Munir, I.A. D'Cruz, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN*. #### Purpose of Study In Caucasians with heart failure, a relative lymphocytopenia (%L) is inversely correlated with jugular venous pressure to implicate splanchnic congestion and the enteric loss of lymphocytes. To address the presence of reduced %L (<20%) in African-Americans (AA) with heart failure and to consider potential pathophysiologic mechanisms influencing lymphocyte count, we monitored AA patients with or without splanchnic congestion and other potential covariants that included hypovitaminosis D and secondary hyperparathyroidism (SHPT). #### Methods Used In 131 AA (90 men; 53 ± 12 yrs): 113 were hospitalized, 50 with decompensated biventricular failure (DecompHF); 24 with acute left heart failure (LHF); 39 with heart disease, but no heart failure (HDNHF); and 18 were outpatients with compensated failure (CompHF). At the time of admission or outpatient visit, we monitored: white blood cell count (WBC#); total lymphocyte count (L#) and %L; 25(OH)D; and parathyroid hormone (PTH). We again monitored L# and %L weeks after medical management had resolved splanchnic congestion. #### Summary of Results WBC# did not differ amongst the 4 groups; while %L was reduced (*P* < 0.05) only in those with DecompHF (15 ± 1%; *P* < 0.05) vs. 25 ± 2% with LHF, 29 ± 1% in HDNHF, and 28 ± 3% in CompHF. Likewise, total L# was significantly (*P* < 0.05) reduced in DecompHF compared to the other hospitalized patients and to outpatients with CompHF: DecompHF, 1069 ± 76; acute LHF, 1529 ± 129; HDNHF, 1915 ± 92; and compensated, 2087 ± 519. Reduced 25(OH)D (<30 ng/mL), in keeping with hypovitaminosis D, was found in all AA, and therefore was not likely to be contributory. Elevated serum PTH (>65 pg/mL) was present only in those with DecompHF (123 ± 22 pg/mL). Lymphocytopenia corrected weeks after the reversal of splanchnic congestion. #### Conclusions A relative and absolute lymphocytopenia, together with elevated PTH, were found in AA hospitalized with DecompHF, but not AA hospitalized with acute LHF or HDNHF or AA outpatients with CompHF. These findings implicate splanchnic congestion and an enteric loss of lymphocytes as contributing to lymphocytopenia. The role of SHPT remains to be determined. ### 256 MEASUREMENT OF IMPAIRED CORONARY VASCULAR REACTIVITY USING 3T MRI IN ASYMPTOMATIC WOMEN WITH TYPE 2 DIABETES C. Maroules2, H. Yadav3, R. Peshock1, A.Y. Chang1 * 1UT Southwestern Medical Center, Dallas, TX; 2UT Southwestern Medical Center, Dallas, TX and 3UT School of Public Health, Dallas, TX*. #### Purpose of Study Although cardiovascular (CV) mortality rates are declining for men, deaths for women with diabetes (DM) have increased 23% over the past 30 years. Because women are more likely to be diagnosed with CV disease during their first CV event, there is a great need for improved detection of subclinical disease in women. One potential diagnostic target is impaired coronary vascular reactivity (CVR). Women with chest pain are more likely to have abnormalities of CVR before obstructive coronary artery disease can be detected by invasive angiography. Changes in coronary flow velocity have been successfully measured by magnetic resonance flow mapping at 1.5T. We tested if impaired CVR, as determined by coronary flow velocity reserve, could be measured in asymptomatic women with DM using 3T MRI. #### Methods Used Pre-menopausal women with DM and healthy, overweight controls provided informed consent approved by the institutional review board. Subjects were placed supine in a 3T MRI scanner (Achieva, Philips, Best, NL). Baseline coronary velocity measurements were obtained using a VCG triggered breath-hold, velocity-encoded spiral cine sequence perpendicular to the RCA (spatial resolution = 0.8 x 0.8 x 7 mm3, temporal resolution = 69 ms). Images of the RCA were acquired during 3 minutes of the cold pressor test (CPT), a well-validated test of endothelial-mediated vasodilatation, and during 10 minutes of recovery. Coronary flow velocity reserve was calculated as peak diastolic velocity during stress divided by baseline peak diastolic velocity. #### Summary of Results The mean age of women with DM (n = 4) was 44.5 ± 4.7 (mean ± SD) with a BMI of 32.6 ± 5.1 [healthy subjects (n = 7), age 35.1 ± 6.5, BMI 25.1 ± 1.8]. Rate-pressure product increased 46.0 ± 23.0% from baseline to peak CPT in controls v 20 ± 13% in women with DM. There was a significant difference in both the percent increase in peak diastolic flow velocity (DM 32.7 ± 5.6%, controls 82.7 ± 29.2%, *P* = 0.02) and coronary flow velocity reserve (DM 1.32 ± 0.07, controls 1.83 ± 0.29, *P* = 0.01). #### Conclusions Measurement of coronary flow velocity reserve using 3T MRI can detect a significant decrease in endothelial-mediated CVR in asymptomatic women with type 2 diabetes. ### 257 A PROTEIN-LOSING ENTEROPATHY IN PATIENTS WITH DECOMPENSATED, BIVENTRICULAR FAILURE HAVING HYPOALBUMINEMIA D.L. Battin, S. Ali, A.D. Whitted, M.D. Nelson, R.C. Davis, J.D. Massie, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN*. #### Purpose of Study Hypoalbuminemia is known to occur in patients having hepatic and splanchnic congestion of diverse etiologic origins. Potential causes include: impaired hepatic protein synthesis; poor nutrition; and gastrointestinal loss, or a protein-losing enteropathy (PLE). We employed radionuclide imaging with technetium (Tc)-labeled dextran70 to address the presence of PLE in patients with decompensated biventricular failure (DecompHF), who on admission were found to have hypoalbuminemia (serum albumin <3.2 g/dL) of uncertain causality. #### Methods Used Twenty-one patients (17 M; 55.4 ± 2.2 yrs) were hospitalized having DecompHF with reduced ejection fraction (EF <30%) due to an ischemic or nonischemic cardiomyopathy. They presented with clinical and echocardiographic evidence of systemic venous hypertension, which respectively included jugular venous distention, tricuspid regurgitation, bilateral lower extremity edema, and dilation of the inferior vena cava without respiratory variation. Admission serum albumin was 2.67 ± 0.08 g/dL. Intravenous Tc-Dex70 and subsequent imaging of the gastrointestinal tract was carried out at 1 and 3 hrs post-dosing. #### Summary of Results A positive scan with Tc-Dex70 within the small and large intestine (without nonspecific appearance of Tc in salivary glands, thyroid or stomach) was found in 10 patients (48%) and in whom serum albumin improved to >3.0 g/dL with the resolution of splanchnic congestion by medical management to suggest a reversible PLE, confirmed by negative follow-up Tc-Dex70 scan in some cases. In 11 patients, the TC-Dex70 scan was negative and hypoalbuminemia persisted after resolution of hepatic and splanchnic congestion by medical therapy suggesting other factors contributed to their reduced serum albumin. #### Conclusions In patients with DecompHF having splanchnic congestion and hypoalbuminemia the enteric loss of albumin and the presence of a PLE should be considered as a causal factor and which can be reversed by medical management. ### 258 INSULIN-LIKE GROWTH FACTOR I DOWNREGULATES LIPOPROTEIN LIPASE AND SUPPRESSES ATHEROSCLEROTIC FOAM CELL FORMATION IN VIVO AND IN VITRO S. Sukhanov, C. Vaughn, Y. Higashi, S. Shai, P. Delafontaine *Tulane University, New Orleans, LA*. #### Purpose of Study We have shown that insulin-like growth factor I (IGF-1) decreases atherosclerotic burden in ApoE-null mice. Lipoprotein lipase (LPL) increases the uptake of oxidized low density lipoprotein (OxLDL) by macrophages (MΦ), promoting foam cell formation and atherosclerosis. The purpose of this study to determine a potential effect of IGF-1 on LPL and foam cell formation in vivo and in vitro. #### Methods Used ApoE-null mice were infused with IGF-1 (1.5 mg/kg) or saline for 12 weeks, foam cells were quantified by Oil Red positivity and MΦ - by immunostaining with Mac-3 a/b. LPL activity - fluorescence assay, gene expression - RT-PCR, LDL binding - fluorescent DiI-OxLDL assay and OxLDL uptake - Oil Red staining. #### Summary of Results IGF-1 reduced aortic LPL mRNA levels by 31% and serum LPL activity by 66%. This effect correlated with a 27% reduction in Oil Red-positive aortic valve lesion area and a 36% decrease in plaque MΦ levels suggesting that IGF-1 reduced MΦ-derived foam cell formation. To determine the role of IGF-1 and LPL in foam cell formation, human blood monocyte- or THP-1 cell-derived MΦ were treated with OxLDL (80 ug/ml, 48 h) to stimulate formation of Oil Red-positive "foam cells". OxLDL increased MΦ LPL mRNA levels and LPL activity >5-fold and decreased MΦ IGF-1 receptor (IGF1R) levels by 65%. IGF-1 (25 ng/ml, 24h) reversed OxLDL-induced upregulation of LPL activity (52% inhibition) and decreased lipid uptake by 88%. Furthermore, overexpression of IGF1R in MΦ with an adenovirus encoding IGF1R prevented lipid uptake by 82% vs. control Ad-GFP-infected MΦ. Conversely, addition of 5 ug/ml exogenous LPL increased DiI-OxLDL binding by MΦ (2.3-fold increase) and lipid uptake (1.9-fold increase). Liver X receptor (LXR) is a nuclear transcription factor regulating MΦ LPL expression. The LXR agonist 22R-oxycholesterol (50 uM, 16h) markedly increased LPL activity in MΦ (>2-fold) and IGF-1 reversed this effect by 65%. #### Conclusions Our data indicate that IGF-1 downregulates LPL in vivo and in vitro potentially via a LXR-dependent mechanism and inhibits foam cell formation. This is the first report of an effect of IGF-1 on cellular lipid internalization and these findings have major relevance for the understanding of mechanisms whereby IGF-1 reduces atherosclerosis. ### 259 CARDIOMYOPATHY IN DIABETICS-HISPANIC POPULATION P.I. Altieri, Y. Figueroa, H.L. Banchs, M. Crespo, N. Escobales *University of Puerto Rico, Medical Sciences Campus, San Juan, PR*. #### Purpose of Study A group of 169 diabetics patients were studied to find out the incidence of cardiomyopathy. #### Methods Used A group of 169 diabetics patients were studied to find out the incidence of cardiomyopathy. #### Summary of Results The mean age was 60 years. Fifty seven percent were males and Forty three percent females. The mean body mass index was 30 kg/m2. The mean fasting blood sugar was 169 mg/dl. Ninety Seven percent were diabetic Type II and 3% percent were diabetics Type I. The studied population showed a higher incidence of atrial fibrillation when compared with the control group. (12% vs. 5.9%) *P* < 0.001. The diabetic group showed a subnormal ejection fraction (50 ± 4%) with diffuse hypokinesis when compared with our control group (62 ± 12%) *P* < 0.001. The lipid profile of the group was normal and none showed myocardial infarction or stroke. #### Conclusions This data shows that this Hispanic group with diabetes mellitus does not show significant atherosclerotic disease but a sub-normal ejection fraction with diffuse hypokinesis. We have shown that diabetic patients have higher levels of angiotensin II and endothelin I intracoronary and peripherally. Both peptides will produce apoptosis and necrosis of the myocardial cells by increasing cytosolic CA + +, which will increases intracellular oxidative stress. Also, a reduction of intracellular glutathionine and a reduction of the glutathionine-homocystein ratio will produce the same pathologic process. This data shows that a group of Hispanic diabetics patient will developed myocardial disease irrespective of the presence of coronary artery disease. This is due to others mechanisms, described previously. ### 260 CORRELATES OF COMMON CAROTID ARTERY LUMEN DIAMETER IN BLACK AND WHITE YOUNGER ADULTS: THE BOGALUSA HEART STUDY L. Ruan1,2, W. Chen1, S.R. Srinivasan1, A. Toprak1, G.S. Berenson1 * 1Department of Epidemiology, New Orleans, LA and 2The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China*. #### Purpose of Study Vascular remodeling as depicted by increases in arterial lumen diameter occurs in response to atherosclerosis. However, data on the correlates of arterial lumen diameter in younger adults by race and sex are limited. This study examined the effect of traditional cardiovascular risk factor variables on common carotid artery lumen diameter in black and white young adults. #### Methods Used The study cohort included 739 white and 313 black adults, aged 20-43 years, enrolled in the Bogalusa Heart Study for CV risk factor examination. The common carotid artery lumen diameter at diastole and intima-media thickness (IMT) were measured by M- and B-mode ultrasonography, respectively. #### Summary of Results As a group, blacks vs whites (3.44 mm/m vs 3.37 mm/m, *P* = 0.002) and males vs females (3.45 mm/m vs 3.35 mm/m, *P* < 0.001) had greater height-adjusted lumen diameter. In multivariate analyses of total sample, body mass index (BMI), mean arterial pressure (MAP), heart rate, and carotid IMT were independent predictors of height-adjusted lumen diameter. As shown in the table, the magnitude of the effects of MAP and carotid IMT on height-adjusted lumen diameter, measured as slopes of regression lines, was significantly different between races, with blacks showing greater slopes than whites; interaction effects of BMI and MAP with sex on height-adjusted lumen diameter were also noted, with males showing steeper slopes than females. Importantly, the lumen diameter-carotid IMT relationship was stronger in hypertensives (β = 0.668, *P* = 0.029) than in normotensives (β = 0.346, *P* < 0.001), with *P* = 0.038 for difference in slopes. #### Conclusions Common carotid artery lumen diameter is influenced by IMT, adiposity and blood pressure in a race-and sex-specific manner in asymptomatic young adults, which may have implications for preventive cardiology. View this table: [Table23](/content/57/1/301/T23) Regression coefficients (β) of lumen diameter on MAP, carotid IMT and BMI in race or sex groups ### 261 HERITABILITY AND GENETIC LINKAGE OF LEFT VENTRICULAR MASS, SYSTOLIC AND DIASTOLIC FUNCTION IN HYPERTENSIVE AFRICAN AMERICANS (FROM THE GENOA STUDY) G.J. Blair1, K.L. Klos2, A.D. Penman1, B.D. Blossom1, D. Arnett3, R.B. Devereux4, T. Samdarshi1, E. Boerwinkle1, T.H. Mosley1, E.R. Fox1 * 1Univ of Mississippi Medical Center, Jackson, MS; 2UT School of Public Health, Houston, TX; 3University of Alabama at Birmingham, Birmingham, AL and 4New York Presbyterian Hospital-Weil Cornell Medical Center, New York, NY*. #### Purpose of Study Much of the inter-individual variation in left ventricular structure and function is unexplained by established risk factors and may be due to novel or genetic factors. We used pedigree information and information from 454 tandem markers across the genome to estimate the heritability and linkage of various echocardiographic measures of left ventricular structure and function in a cohort of African American hypertensive sibships. #### Methods Used Left ventricular mass was calculated according to the ASE simplified cubed equation and indexed to height. Fractional shortening was calculated as the percent change in the internal diameter between diastole and systole. Ejection fraction was determined by visual assessment. Peak mitral early and late diastolic filling velocities were measured from the transmitral pulsed Doppler scanning trace. The maximum likelihood heritability estimate for each phenotype was obtained using a variance components method. Linkage analyses were performed using the multipoint variance component-based approach. #### Summary of Results There was moderate heritability for left ventricular mass index (34%), interventricular septal wall thickness (29%), diastolic diameter (42%), ejection fraction (40%), fractional shortening (39%), and mitral early and late diastolic filling velocities (37% and 45% respectively). The greatest evidence of genetic linkage was observed for LV mass index and relative wall thickness on chromosome 3 (LOD scores of 2.38), LV ejection fraction on chromosome 12 (LOD score = 2.39), and mitral E velocity on chromosome 19 (LOD score = 2.69). #### Conclusions In conclusion, in this African American cohort of hypertensive sibships, the greatest evidence for linkage of left ventricular structure and function was on choromsomes 3, 12 and 19. ## **Gastroenterology and Clinical Nutrition I Concurrent Session** 2:00 PM Friday, February 13, 2009 ### 262 EFFECT OF SPECIFIC TRIPLEX FORMING OLIGONUCLEOTIDES TO TYPE I COLLAGEN PROMOTER ON DMN-INDUCED LIVER FIBROSIS N. Baburyan1, S. Koilan2, D. Hamilton3, R. Guntaka2 * 1UTHSC, Memphis, TN; 2UTHSC, Memphis, TN and 3UTHSC, Memphis, TN*. #### Purpose of Study Triplex-forming oligonucleotides (TFOs) bind to duplex DNA at polypurine/ polypyrimidine stretches in a sequence-specific manner. The binding specificity of TFOs allows for directed modification of gene expression. In this study we developed type alpha1(I) promoter specific TFOs to inhibit transcription of collagen gene in the rat model of liver fibrosis. #### Methods Used Three groups of 6-wk-old Sprague-Dawley rats: control - treated with saline only; DMN - treated with i.p. injections of 1% DMN every other day for 4 weeks; and DMN + TFO group - received i.p. TFO (4 mg/kg body weight) concomitant with DMN. We monitored liver/body weight as a marker of liver injury. RT-PCR was used to quantitate the transcription of type I collagen mRNA relative to housekeeping gene cyclophillin. The expression of type III collagen mRNA was also evaluated to test for the specificity of TFO effect. The gene expression in the treatment groups was calculated as fold change relative to the control. Data for liver/body weights were expressed as mean ± SD. #### Summary of Results Four weeks of DMN treatment led to hepatic necrosis and fibrosis shown by decreased liver/body weight and overexpression of type I and III collagen mRNAs. TFO treatment resulted in 2.7-fold decrease in collagen type I mRNA expression. TFOs did not affect the expression of type III collagen mRNA suggesting that the inhibition of collagen type I mRNA was sequence-specific. TFO-treated rats also tended to have higher liver/body weight ratio (Table 1). View this table: [Table24](/content/57/1/301/T24) #### Conclusions Treatment with TFOs attenuated development of liver fibrosis after DMN-induced liver injury by specific inhibition of transcription of collagen type I gene. Thus, TFOs present a potentially valuable strategy for effective treatment of chronic fibrotic disease of liver. ### 263 PROHIBITIN IS A NOVEL ANTIOXIDANT THAT ATTENUATES COLONIC INFLAMMATION IN MICE A.L. Theiss1, M. Vijay-Kumar2, T.S. Obertone1, D.P. Jones3, J.M. Hansen4, A.T. Gewirtz2, D. Merlin1, S.V. Sitaraman1 * 1Emory University, Atlanta, GA; 2Emory University, Atlanta, GA; 3Emory University, Atlanta, GA and 4Emory University, Atlanta, GA*. #### Purpose of Study Increased free radicals and/or impaired antioxidant defenses have been shown to play a pathogenetic role in human and animal models of inflammatory bowel disease. Our previous studies showed that prohibitin (PHB) levels are decreased during colitis and that cultured intestinal epithelial cells overexpressing PHB are protected from oxidative stress. This study investigated the effect of intestinal epithelial cell-specific PHB overexpression on oxidative stress associated with experimental colitis and the potential mechanism by which PHB functions as an antioxidant using PHB transgenic mice. #### Methods Used Colitis was induced using two established mouse models (S. typhimurium and dextran sodium sulfate) in PHB transgenic mice and wild-type littermates. Oxidative stress was determined by measuring glutathione and protein carbonyl levels in the cecum or colon. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcriptional regulator of oxidant responses, expression and activation was assessed in colon mucosa and cultured intestinal epithelial cells overexpressing PHB. #### Summary of Results Cells overexpressing PHB showed sustained Nrf2 nuclear accumulation and DNA binding during oxidant stress. PHB transgenic mice exhibited decreased oxidative stress and colitis and increased Nrf2 mRNA expression, nuclear protein translocation and DNA binding compared to wild-type littermates during colitis. #### Conclusions These results demonstrate that PHB is a regulator of Nrf2 expression in intestinal epithelial cells during oxidative conditions and prevents inflammation-associated oxidative stress and injury through sustained activation of Nrf2. Our data demonstrate that PHB is a novel antioxidant and suggest that restoration of PHB levels represents a potential therapeutic approach in inflammatory bowel disease. ### 264 DIABETIC GASTROPARESIS: DO DELAYED DIABETICS DIE DIFFERENTIALLY? R.C. Humble2, R. Bhakta2, D. Spree1, T. Cutts3, W.D. Johnson4, T.L. Abell1 * 1University of Mississippi Medical Center, Jackson, MS; 2University of Mississippi, Jackson, MS; 3University of Tennessee Memphis, Memphis, TN and 4University of Mississippi medical Center, Jackson, MS*. #### Purpose of Study Diabetic gastoparesis (GP) has been associated with high mortality, and at risk factors for death are unknown. We aimed to investigate the relationship between baseline measures and survival. #### Methods Used Over a 13 year period, we evaluated 97 patients (mean age at baseline = 46.2) with diabetic gastroparesis and assessed them for GP symptoms (vomiting (V), nausea (N), early satiety, bloating, abdominal pain, and a total symptom score (TSS) (max score = 4 for each symptom, TSS max score = 20)), quality of life (QOL) based on the IDIOMS scale, 4 hour gastric emptying time (4hGET), and survival. Within the group there were 31 male, 66 female. #### Summary of Results 29 of 68 patients had non-delayed gastic emptying, and none of these patients died. 68 were delayed, and 13 of these patients died. All 13 had characteristics that separated them from the patients who did not die. Baseline measurements from patients that died showed significant differences in delayed 4hGET, impaired QOL, and greater vomiting. However, there was no significant difference in symptoms of N or in TSS. Furthermore, among the delayed subgroup of patients, there were significant baseline differences in three criteria of V, 4hGET, QOL between those that died vs. patients surviving (See Table). Alive patients have survived an average of 43 months since baseline measurements were taken, while the 13 deceased patients survived an average of 20 months. #### Conclusions In this 13-year evaluation, distinct subsets of diabetic gastroparesis patients presenting with severely delayed gastric emptying, high instances of vomiting, and poor quality of life at baseline appear to be the patients most likely to die. Further efforts may be warranted in the treatment of this subset of diabetic gastroparesis patients. View this table: [Table25](/content/57/1/301/T25) ### 265 ZOLLINGER-ELLISON SYNDROME: PROSPECTIVE EVALUATION OF CLINICAL CHARACTERISTICS, RESPONSE TO THERAPY AND OUTCOME C.M. Wilcox, J. Arcury, T. Seay, B.I. Hirschowitz *University of Alabama at Birmingham, Birmingham, AL*. #### Purpose of Study Zollinger-Ellison syndrome (ZES) is a rare but likely under diagnosed condition associated with gastric acid hypersecretion and potentially life-threatening upper gastrointestinal disease. Most data in the United States has come from the National Institutes of Health. We evaluated the clinical characteristics, response to therapy and long-term outcome of a cohort of patients with ZES. #### Methods Used Retrospective series of prospectively collected data obtained over an 18 year period at the University of Alabama at Birmingham. #### Summary of Results 70 patients (56% male, mean age 54 years; range- 29-88) were diagnosed with ZES using standard criteria. The most common presentation was complicated peptic ulcer and the mean duration of symptoms was 13.5 years. While diarrhea was a complaint in 30 patients (43%), 1 patient presented with chronic diarrhea alone. 15 patients (21%) had associated MEN-1 syndrome. Long term follow-up (>3 mon) was available in 64 patients where gastric acid secretion was titrated on variable dose lansoprazole. The mean effective dose was 93.91 mg/day (median 60 mg/day) (range 35 mg/day-370 mg/day) and all patients had gastric acid secretion controlled. The median follow-up was 5.4 years and 4 patients died related to malignant gastrinoma. #### Conclusions Zollinger-Ellison syndrome presents in a typical fashion, lansoprazole was uniformly effective in healing mucosal disease and normalizing gastric acid secretion, and long term survival was good without surgery. ### 266 PROBIOTIC ESCHERICHIA COLI INDUCES INTERFERON-ALPHAA AND UP-REGULATES GUANYLATE BINDING PROTEIN-1 IN INTESTINAL EPITHELIUM J. Mirpuri, P.W. Lin, N.A. Louis *Emory University, Atlanta, GA*. #### Purpose of Study Necrotizing enterocolitis (NEC) is a clinically significant intestinal inflammatory disease in preterm infants. Experimental evidence indicates that aberrant apoptosis in the immature intestine leads to an exaggerated immune response in NEC. Probiotic bacteria modulate inflammation and prevent apoptosis and recent studies suggest probiotics may prevent NEC. Our goal was to identify downstream mediators of probiotic effects on inflammation and apoptosis in a murine model of immature intestine. Probiotic E. coli in this model have been shown to reduce staurosporine-induced apoptosis. Candidate target mediators of these probiotic effects include interferon alphaA (IFNαA) and the interferon-responsive, anti-apoptotic membrane protein Guanylate Binding Protein 1 (GBP-1). We hypothesized that probiotic exposure protects against apoptosis in immature mouse intestine through the upregulation of IFNαA and its downstream target GBP-1. #### Methods Used 2 week-old neonatal mice were gavage fed 109-1010 CFUs of a probiotic strain of E. coli. At 4,24 and 48 hours mice were sacrificed, colons were isolated for RNA, and cDNA was prepared. Expression of inflammatory cytokines including IFNαA and GBP-1 were determined by real-time PCR at baseline and following exposure to probiotic E. coli. #### Summary of Results Baseline cytokine profiling revealed that immature intestine is proinflammatory relative to adult controls with increased interferon gamma, decreased IL-10 and decreased IFNaA. Probiotic treatment of 2 week-old mice resulted in a significant up-regulation of IFNa and the interferon inducible protein GBP-1 by 24 hours relative to controls. These changes occurred in the background of reduced staurosporine induced apoptosis in the intestine of the probiotic fed mice. #### Conclusions Probiotic E-coli exposed 2 week old mouse intestine shows increased IFNαA and GBP-1 mRNA expression compared to age matched controls. IFNαA and GBP-1 may be significant, through their reduction of apoptosis and promotion of barrier function, in the prevention of necrotizing enterocolitis. ### 267 URINARY NITRATE AS A MARKER OF DISEASE ACTIVITY AND RESPONCE TO INFLIXIMAB THERAPY IN PATIENTS WITH CROHNS DISEASE A. Sheth, E. Salvatiera, S. Hussain, A. Minocha, J.S. Alexander, P. Jordan, K. Manas *Louisiana State University Health Sciences Center, Shreveport, LA*. #### Purpose of Study Various biological markers of inflammation have been used for diagnosis and assessment of prognosis and success of therapy in IBD; however an ideal marker has not been established yet. Estimation of nitrite is a useful marker of NO synthesis which is induced by pro-inflammatory cytokines in patients with IBD. Our study evaluates the role of urinary nitrite as a marker of inflammation and response to treatment in Crohns disease. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F15.medium.gif) [Figure.](/content/57/1/301/F15) Figure.   #### Methods Used Over a period of three months, patients with an established diagnosis of Crohn's disease were selected for the study. Three groups of patients underwent urinary nitrite assessment, 22 patients with Crohn's disease who were naïve to infliximab, 14 patients with Crohn's disease who were currently receiving infliximab treatment and 15 controls without history of Crohn's disease. Urinary nitrite levels were performed using the standard Griess assay as described by Grisham and his colleagues. #### Summary of Results In the control group, the mean urinary nitrite level was 3.13 + /- 1.186 micromoles (n = 15). In infliximab naive group mean urinary nitrite level was 34.26 + /- 8.24 micromoles (n = 22) compared to 10.58 + /- 3.13 micromoles in patients were Crohn's disease who were currently treated with infliximab (n = 14; *P* < 0.001 vs. infliximab naïve group) (Table 1). #### Conclusions Our study suggests a potential role of urinary nitrate both as a marker of disease activity and an indicator of response to infliximab therapy in patients with Crohns disease. ### 268 IDENTIFICATION OF CFTR AND SLC26A6 IN THE ESOPHAGEAL SUBMUCOSAL GLANDS S. Abdulnour-Nakhoul1,2, R. Doetjes2, N. Nakhoul1 * 1Southeast Louisiana Veterans Health Care System, New Orleans, LA and 2Tulane Medical Center, New Orleans, LA*. #### Purpose of Study Cystic fibrosis transmembrane conductance regulator (CFTR) channels are cAMP-regulated Cl- channels present on the apical membrane of various epithelial cells. CFTR channels, in conjunction with the anion transporter SLC26A6, play an important role in HCO3- secretion in glandular tissues. CFTR channels are defective in cystic fibrosis (CF) patients. One of the gastrointestinal manifestations of cystic fibrosis (CF) is gastro-esophageal reflux disease (GERD). The esophageal submucosal glands (SMG) secrete bicarbonate and mucus in the esophageal lumen which play a role in esophageal protection. We have previously demonstrated that an increase in intracellular cAMP caused by forskolin, an adenylyl cyclase activator, or IBMX, a phosphodiesterase inhibitor, resulted in a large increase in basal HCO3- secretion. In this study we investigated the presence of CFTR and SLC26A6 in the esophageal tissue #### Methods Used We have used the reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) to detect CFTR and SLC26A6 in the pig esophageal tissue. #### Summary of Results We isolated RNA from dissected SMG and the esophageal stratified squamous epithelium (SSE). After preparation of cDNA, appropriate forward and reverse primers were used for reverse transcription and amplification of CFTR and SLC26A6. Expression of CFTR was confirmed in the SMG but not in the SSE, and expression of SLC26A6 was confirmed in SMG and SSE, as determined by amplification of the expected product sizes, respectively. Our IHC experiments indicated the presence of CFTR in the mucous and duct cells of the esophageal SMG. The localization of CFTR is diffuse in the mucous cells and more localized to the luminal membrane in the ducts. We also localized SLC26A6 to the luminal membrane of the duct cells by IHC, a finding consistent with a role of this transporter in luminal transport of HCO3- #### Conclusions These results confirm the presence of CFTR channels and of SLC26A6 in the esophageal SMG and might explain in part the occurrence of GERD in CF patients. The role of SLC26A6 in the SSE remain to be determined ### 269 SURVIVAL IN PATIENTS WITH GASTROPARESIS: GES DEVICES VS. CONTROL PATIENTS R. Bhakta2, R.C. Humble2, T. Cutts4, D. Spree1, W.D. Johnson3, T.L. Abell1 * 1University of Missippi Medical Center, Jackson, MS; 2University of Missippi Medical Center, Jackson, MS; 3University of Missippi Medical Center, Jackson, MS and 4University of Tennessee Memphis, Memphis, TN*. #### Purpose of Stud Gastroparesis (GP), a clinical syndrome associated with nausea/vomiting and disordered gastric emptying, is associated with significant morbidity and mortality. We previously examined a large group of GP patients to see what baseline characteristics might be associated with later mortality and now report on the effect of GES devices on survival. #### Methods Used We examined 441 consecutive patients (81 m, 360 f, mean age 43 years, with Dx: 264 ID, 114DM and 63 post-surgical disorder) with GP symptoms seen over a 15 year period. All patients had the symptoms of nausea, vomiting, early satiety/anorexia, bloating/diarrhea, and/or abdominal pain. Patients were also stratified by the results of a low fat gastric emptying test as delayed or not at 4 hours (>10%). From this data base 430 patients had complete data: 271 patients had been implanted and 159 had been evaluated but not implanted. From the time of evaluation and/or implant, survival at 24 months was compared using a standard Kaplan-Meier survival curve. #### Summary of Results Mean survival was longer for GES implanted patients (23 months) vs controls (21.9 months), *P* = 0.02. Results for each diagnostic subgroup were similar (*P* = 0.7) but for diabetic patients survival was longer for GES (23.3 months) Vs Control (20.1 months) although this was not statistically significant (*P* = 0.2). Delayed diabetic GES patients also survived longer (23.3 months) than control patients (18.4 months). (See Table 1) #### Conclusions GES devices are associated with significantly improved survival at 24 months Vs control patients. This improvement in survival is especially seen in patients with Diabetic gastroparesis, and especially those with delayed gastric emptying. View this table: [Table26](/content/57/1/301/T26) Survival Among GP Patients (GES Implanted vs. Control) ### 270 IMPORTANCE OF BASELINE MUCOSAL ELECTROGASTROGRAM IN CYCLIC VS. NONCYCLIC SYMPTOM PATTERNS IN GASTROPARETICS WITH GASTRIC ELECTRICAL STIMULATION J. Williams, E.S. Weeks, T.L. Abell *University of Mississippi Medical Center, Jackson, MS*. #### Purpose of Study While most patients with gastroparesis (GP) symptoms have chronic symptoms, others have symptoms that are cyclic in nature. We previously reported that patients with cyclic symptoms (Cyc) differed from those with no cyclic symptoms (NoCyc) in several ways (AJG 101(9),2006). We now investigate baseline endoscopic mucosal EGG results to determine differences between Cyc vs NoCyc patients. #### Methods Used We examined 48 patients (8 m, 40 f, mean age 41.5 yrs, with Dx: 18 ID, 27 DM and 3 Post-Surgical disorders) with drug refractory GP symptoms referred for possible GES. 35 patients (3 m, 32 f) had Cyc symtoms, and 13 (1 m, 12 f) had NoCyc symptoms. 38 of 48 pts (25 Cyc and 13 NoCyc) underwent implantation of permanent GES, mean of 33 months after undergoing a trial of temporary GES, when a mucosal EGG was obtained. The mucosal EGG was reported as frequency (Freq) in CPM, amplitude (Amp) in mV, and Freq/Amp ratio (FAR). Results were compared by paired t-tests, baseline vs. latest for GES patients, and reported as mean values. #### Summary of Results Cyc patients were similar to NoCyc patients with the exception of solid 4-hour gastric emptying (GET4) and health related quality of life (QOL), both of which were more impaired in Cyc Vs NoCyc patients. After GES placement, improvement in all parameters was greater in Cyc than NoCyc patients (See table). Baseline mucosal EGG frequency was lower in Cyc vs NoCyc (3.94 vs 5.25, *P* = 0.055) and amplitude was higher in Cyc vs NoCyc (0.55 vs 0.11, *P* = 0.093). FAR was also lower in Cyc vs NoCyc (39.6 vs 57.2, *P* = 0.39). #### Conclusions Based on this sample, GP patients with cyclic symptoms respond better to GES than those without cyclic symptoms. This could be related to the finding that mucosal EGG in cyclic patients are more normal when compared to non-cyclic patients. Mucosal EGG may be a useful tool for predicting which patients will respond to GES. View this table: [Table27](/content/57/1/301/T27) ### 271 GASTRIC ELECTRICAL STIMULATION -10 YEARS EXPERIENCE WITH CLINICAL OUTCOME ANALYSIS BEYOND 5 YEARS OF ENTERRA THERAPY IN A DRUG- REFRACTORY GASTROPARESIS I. Sarosiek1, R. Hejazi1, K. Roeser1, J. Forester2, J. Sarosiek1, R.W. McCallum1 * 1Kansas University Medical Center, Kansas City, KS and 2Kansas University Medical Center, Kansas City, KS*. #### Purpose of Study We present results of symptomatic response, nutritional status (BMI, TPN, G-J- tubes), diabetes control (HA1c level), hospitalization rate, and need for prokinetic/anti-emetic drugs, as well as to analyze complications experienced by patients with gastroparesis (GP) implanted with gastric electrical stimulation (GES) at the single site over the last 10 years. #### Methods Used Totally 234 patients (77% F; 64% DM, 21%ID and 15%PS) mean age 41 (20-71) were implanted with GES since April 1998. Patients with at least 5 years of FU were analyzed for total GI-GP symptoms score (TSS), nutritional status, GP-specific medications use, and days of hospitalization in year before GES and in a last year. The incidence and spectrum of complications were also identified. #### Summary of Results 48 patients out of 95 (41 F; 25DM, 14ID, 9PS) with mean duration of 6, 5 years (range 5-10) of FU were available for this analysis. The TSS of severity of GP symptoms decreased from 21 to 7 points (*P* < 0.001 and frequency improved from 22 to 8 points (*P* < 0.001) Mean HbA1c level went down from 8, 8 to 7.9, and weight remained stable 136 vs. 154lbs. There was 40% reduction in use of GP drugs. Only 3 J-tubes were still remained at FU out of 15 J-tubes, 6 G-tubes and 3 TPN lines present before Enterra therapy. Number of hospitalization days decreased significantly from 48 to 2,3 (*P* < 0.001).We encountered 24 (10%) deaths out of 234 implanted patients with 92% cases related to cardio-vascular and renal complications in DM. 12% Enterra patient had a system removed with 6% infection rate, and 5%requered surgical revision due to dislodgement of the electrodes. #### Conclusions 1) GES provides an excellent clinical outcome sustained up to 10 years in majority of complicated GP patients with significant reduction in GI symptoms, hospitalizations, and GP specific medication use with improvement of nutritional status and HbA1 level. 2) There were not deaths occurring from malfunctioning or technical issues related to the presence of Enterra device 3) Since number of Enterra patients is increasing steadily an awareness of complications need to be noted. ## **Hematology and Oncology I Concurrent Session** 2:00 PM Friday, February 13, 2009 ### 272 RESPONSE OF ANAPLASTIC THYROID TUMORS TO VEGF-TRAP, AN ANTI-ANGIOGENIC AGENT S.I. Khan, I.T. Rossi, I.C. Mitchell, F.E. Nwariaku *UT Southwestern, Dallas, TX*. #### Purpose of Study Vascular Endothelial Growth Factor(VEGF) is an important target for cancer therapy. Monoclonal antibodies targeting VEGF Receptor 2, responsible for endothelial activation during angiogenesis, have not proven efficacious in clinical studies. VEGF-Trap, a synthetic protein targeting both VEGFR1 and VEGFR2 has a higher binding affinity for VEGF than monoclonal antibodies. This study examined the effect of VEGF-Trap in anaplastic thyroid carcinoma cells, an aggressive form of thyroid cancer with a high mortality rate. #### Methods Used We developed an orthotopic model of human anaplastic thyroid cancer by injecting human anaplastic thyroid carcinoma cells (DRO'90, Dr. Guy Juillard Univ. of California), into the right thyroid lobe of mice. Six weeks later, the mice were i.p. injected with either VEGF-Trap bi-weekly (doses ranging from 2.5-25 mg/kg) or human Fc control for 5 weeks. Vehicle and Trap-treated (25 mg/kg) frozen tumor sections were used for immunostaining to determine tumor vessel maturity and macrophage infiltration. Primary antibodies used were F4/80 (Serotec), T014 (rabbit anti-VEGFR2), and CD140b (rat anti-PDGFR-β). The appropriate secondary antibody was used. Tumor microvessel density was determined by counting blood vessels in 6 high-power fields per slide (200x). Pericyte-associated vessels were similarly identified. VEGF protein concentrations were measured in tumor tissue homogenates via ELISAs. #### Summary of Results After 30 days, VEGF treated mice showed improved survival compared to controls (100% v 40%,*P* < 0.05). Tumor size was significantly smaller by 0.5gram in the Trap-treated group. Anaplastic tumors treated with Trap demonstrated a significant decrease in microvessel density compared to controls (33 v 17 vessels/hpf,*P* < 0.005). Fluorescence images of tumors stained with endothelial marker CD34 and pericyte marker α-SMA, show that VEGF-Trap treatment reduced the overall density of mature and immature vessels (*P* < 0.005). A compensatory increase in VEGF production by host cells was seen in high-dose VEGF-Trap treated mice, not in tumor cells (6000 pg/mg lysate v 900 pg/mg lysate, *P* < 0.005). #### Conclusions Anaplastic thyroid cancer is susceptible to treatment with VEGF-Trap. Treatment with VEGF-Trap improved survival in an orthotopic mouse model of human anaplastic thyroid carcinoma indicated by a smaller tumor size and lower microvessel density. ### 273 NICOTINE STIMULATES PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR BETA/DELTA GENE EXPRESSION IN HUMAN LUNG CARCINOMA CELLS THROUGH NICOTINIC ACETYLCHOLINE RECEPTOR-MEDIATED ACTIVATION OF MULTIPLE KINASE SIGNALING PATHWAYS AND REDUCTION OF ACTIVATION PROTEIN-2ALPHA S. Han1, X. Sun1, J. Ritzenthaler1, Y. Zheng1, J. Roman1,2 * 1Emory University, ATlanta, GA and 2Atlanta Veterans Affairs Medical Center, Atlanta, GA*. #### Purpose of Study We previously demonstrated that nicotine stimulates non small cell lung carcinoma (NSCLC) cell proliferation through nicotinic acetylcholine receptor (nAChR)-mediated signals. Activation of peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) has also been shown to induce NSCLC cell growth. Here, we explore the link between nicotine and PPARβ/δ in NSCLC cell survival signals. #### Methods Used Western blot, siRNA, Immunoprecipitation and Transfection assays were used to detect the effect of nicotine on PPARβ/δ protein expression and the roles of α7 nAChR, PPAR co-activator, PGC-1α, and AP-2α in mediating the effect of nicotine on expression of PPARβ/δ and cell growth. Finally, electrophoretic gel mobility shift (EMSA) and ChIP assays were performed to determine the role of AP-2α in this process. #### Summary of Results We found that nicotine increased the expression of PPARβ/δ protein; which was blocked by a α7 nAChR antagonist, by α7 nAChR siRNA, and by inhibitors of PKC, PI3-K, and mTOR signaling. Silencing of PPARβ/δ attenuated the stimulatory effect of nicotine on cell growth, but his was overcome by transfection of cells with an exogenous PPARβ/δ expression vector. Of note, nicotine induced complex formation between α7 nAChR and PPARβ/δ protein, which required recruitment of the PGC-1α. Nicotine also increased PPARβ/δ promoter activity through inhibition of AP-2α, and silencing of AP-2α enhanced the stimulatory effect of nicotine. EMSA and ChIP assays showed that nicotine reduced AP-2α binding to DNA sequences in the promoter region of PPARβ/δ gene. #### Conclusions Our results demonstrate that nicotine increases PPARβ/δ gene expression through PGC-1α and α7 nAChR-mediated activation of PKC/PI3-K/mTOR signals that inhibit AP-2α protein expression and DNA binding activity to the PPARβ/δ gene promoter. This study unveils a novel mechanism by which nicotine promotes human lung carcinoma cell survival. ### 274 CHARACTERIZATION OF RADIATION-ARREST DEFECTIVE ZEBRAFISH MUTANT R612 D. Zhang1, D. Verduzco1, J. Amatruda2 * 1UT Southwestern, Dallas, TX and 2UT Southwestern, Dallas, TX*. #### Purpose of Study A robust DNA damage response is crucial to the survival of an organism, and failure of this response may lead to cancer and degenerative disease. In response to DNA damage, proteins such as ATM kinase and p53 are activated, leading to cell cycle arrest and DNA repair, apoptosis, or senescence. Through a previous zebrafish genetic screen, we have identified a mutant, R612, which fails to halt mitosis after exposure to radiation. By characterizing the phenotype and genotype associated with R612, we hope to gain additional insight into the DNA damage response pathway. #### Methods Used The phenotype of R612 mutants includes spontaneous apoptosis, radiation sensitivity, failure of cell-cycle arrest post-radiation, and a decreased ability to detect DNA damage. To demonstrate defective cell cycle arrest in R612 mutants, we irradiated wild-type and mutant zebrafish embryos and performed immunohistochemistry for the mitotic marker phosphohistone H3 (pH3). We used Acridine Orange staining to detect apoptotic cells in R612 mutants, and tested whether spontaneous apoptosis is ATM-dependent. Lastly, we assessed whether R612 mutants are able to generate foci of phosphohistone H2AX at sites of DNA damage. #### Summary of Results After 16 Gy irradiation, R612 homozygous mutants displayed excessive pH3-positive cells, indicating defective cell cycle arrest. Staining with Acridine Orange revealed undetectable apoptosis in wild-type zebrafish, clear spontaneous apoptosis in homozygous mutants, and moderate levels of apoptosis in heterozygotes. In the presence of an ATM inhibitor, apoptosis is blunted in R612 mutants. Some embryos exhibited abnormally low H2AX phosphorylation post-irradiation. Using microsatellites linked to the R612 locus, we found a consistent pattern in the abnormally stained embryos. #### Conclusions Our experiments showed that the R612 mutation causes defective cell cycle arrest after radiation. We also showed that R612 mutants exhibit spontaneous apoptosis which is partly ATM-dependent. Microsatellite analysis was consistent with a role for the R612 gene product in H2AX phosphorylation after DNA damage. Taken together, these results further elucidate the role of R612 in DNA damage response. These studies will provide us with a greater understanding of the diseases and disorders associated with defects in DNA damage response. ### 275 CHEMICAL GENETIC DISSECTION OF PRIMORDIAL GERM CELL MIGRATION D.M. Moye1,2, V. Damoulis1,2, J. Amatruda1,2 * 1UT Southwestern Medical Center, Dallas, TX and 2UT Southwestern, Dallas, TX*. #### Purpose of Study Migration of primordial germ cells (PGCs) is essential to normal germ line development and defects in this process may lead to germ cell tumors. The mechanisms of germ cell migration are highly conserved from zebrafish to humans. We used high-throughput chemical genetic techniques to analyze PGC migration in zebrafish. The ultimate goal of our project is to understand the biological basis of germ cell tumors in children. #### Methods Used Zebrafish are well suited for chemical screens because the eggs are externally fertilized allowing us to add drugs or compounds directly to the water housing the fertilized eggs. In addition, germ cells can be easily detected by whole mount in-situ hybridization. We used the Prestwick Chemical Library which represents nearly all FDA approved drugs. Four zebrafish embryos were placed in each well of a multiwell plate. After gastrulation occurred (4 hours post fertilization (hpf), drugs were added during the critical period for PGC migration (4 to 24 hpf). Embryos were fixed and whole mount in-situ hybridization was performed with the primordial germ cell-specific Vasa riboprobe to visualize the germ cells. Primordial germ cell migration was observed and scored in each embryo via light microscope. Wells in which at least two embryos contained ectopic germ cells were classified as potential hits. After deconvolution of the library, putative positives were classified structurally and mechanistically, and retested on a larger scale. #### Summary of Results Over 1000 compounds were tested on over 4000 embryos. Eleven compounds induced abnormal germ cell migration and were considered positive hits. Interestingly, 3 of the compounds were local anesthetics that target a shared membrane ion channel. Other chemical classes included a corticosteroid, beta-blocker and tricyclic antidepressant. #### Conclusions Chemical genetics in zebrafish has efficiently identified a potentially novel role for membrane ion channels in the control of PGC migration. Further experiments are needed to precisely define the molecular mechanism for these effects. In addition to PGCs, this work may shed light on factors controlling migration of other cell types, including metastatic cancer cells. ### 276 MALIGNANT PERIPHERAL NERVE SHEATH TUMOR, A TARGETED TREATMENT B.N. Ngo1, E. Gilmore2, E. Cobos1, R. Tran2 * 1Texas Tech University-Health Science Center, Lubbock, TX and 2Texas Tech University-Health Science Center, Lubbock, TX*. #### Purpose of Study Malignant peripheral nerve shealth tumors (MPNST) are extremely rare soft tissue sarcomas which orignate from peripheral nerve branches or shealths of peripheral nerve fibers. They can arise spontaneously or in association with Type I neurofibromatosis. Most are highly aggressive, rapidly progressive, chemotherapy and radio-insensitive with surgery the only curative modality. The role of molecular aberrations of receptor tyrosine kinase genes PDGFRA, KIT, EGFR, and VEGF in MPNST is limited and no data exist on the use of newer targeted therapies in the treatment of MPNST. We report a case of MPNST expressing positivity for these new markers and demonstrate for the first time a clinical response to targeted therapy. #### Methods Used A 58 year old woman presented with several months history of severe right arm pain and a rapidly growing right cervical/supraclavicular mass. CT scan revealed a large unresectable mass involving right brachial plexus from C6-T2 and encasing adjacent vascular structures. Biopsy of the mass revealed high grade malignancy consistent with MPNST. Treatment with radiation lead to minimal response. Additional immunohistochemical evaluation for C-Kit, EGFR, VEGF, and PDGFRA revealed strong positivity for EGFR, VEGF, and PDGFRA and negative C-Kit. The patient was treated with bevacizumab (VEGF inhibitor) and sunitinib (PDGFRA inhibitor). #### Summary of Results Approximately 2 months after receiving IV bevacizumab and oral sunitinib (without concurrent radiation therapy), significant and durable partial remission was achieved. #### Conclusions This case demonstrates the presense of molecular aberrations of receptor tyrosine kinases, the utility of incorporating newer IHC assays for these aberrations, and suggests that EGFR, VEGF, and PDGFRA should therefore be considered as candidates for targeted therapy trials of MPNST. ### 277 SUCCESSFUL MANAGEMENT OF GELATINOUS TRANSFORMATION OF THE BONE MARROW IN ANOREXIA NERVOSA WITH HEMATOPOIETIC GROWTH FACTORS R.S. Charania1, W. Kern2, S. Chakrabarty3, J. Holter1 * 1Oklahoma University Health Sciences Center, Oklahoma City, OK; 2OUHSC, Oklahoma City, OK and 3OUHSC, Oklahoma City, OK*. #### Case Report Serous atrophy or gelatinous transformation of the bone marrow (GMT), often seen with severe nutritional deprivation in anorexia nervosa (AN), is characterized by replacement of the marrow with hyaluronic acid-like mucopolysaccharide material. Treatment with nutritional support is often temporary. We present the case of a 25 year old female with AN who was admitted with syncope. Laboratory studies showed a WBC count of 2100/mm3, absolute neutrophil count (ANC) of 987/mm3, hemoglobin of 7.8 g/dL, platelet count of 91,000/mm3, corrected reticulocyte count of 1.1%, serum albumin of 2.4 g/dL and erythropoietin of 48 mU/mL. Iron panel, thyroid function, copper, zinc, vitamin B12 and folate levels were normal. Bone marrow biopsy showed abundant acellular eosinophilic material with few scattered erythroid precursors, rare myeloid and megakaryocytic precursors, consistent with serous atrophy. Nutritional support produced weight gain and improved platelet count but no change in the WBC count or hemoglobin. She was then treated with Darbopoetin alfa and her hemoglobin increased to 10 g/dL. Pegfilgastrim was added for additional hematopoietic support. Over the next 26 weeks, her nutritional status declined but she continued to maintain normal blood counts. Most recent tests show hemoglobin of 13.5 g/dL, WBC count of 3900/mm3, ANC of 2457/mm3, platelet count of 219,000/mm3 and corrected reticulocyte count of 3.6%. Repeat bone marrow biopsy reveals normal hematopoiesis with few areas of serous atrophy. Severe caloric deficiency depletes fat stores in the marrow and interferes with release of essential hematopoietic growth factors and cytokines. Use of growth factors in AN has been reported infrequently. We conducted a Medline review of 134 cases of GMT associated with AN published from 1974 to 2008. Only 3 cases were treated with hematopoietic growth factors; two with G-CSF and one with erythropoietin. Since AN is a relapsing condition in young adults posing a high risk for infections, nutritional support alone may be insufficient. We suggest that addition of hematopoietic growth factors may be a useful adjunct for sustained hematopoietic recovery. ### 278 SPONTANEOUS REGRESSION OF HEPATOCELLULAR CARCINOMA,A CASE REPORT AND LITERATURE REVIEW B.N. Ngo, E. Cobos *Texas Tech University-Health Science Center, Lubbock, TX*. #### Purpose of Study Hepatocellular carcinoma (HCC) is the 4th leading cause of cancer-related death in the world. It is an aggressive tumor that has poor outcome with estimated median survival following diagnosis of 6 to 20 months. Spontaneous regression (SR) of cancer is extremely rare. We report a case of true SR of HCC in a man who received no treatment. Also, we review reported cases of HCC that spontaneously regressed during the past 30 years. #### Methods Used Case report: A 48 year old Hispanic male with remote history of alcoholism presented with severe right upper quadrant abdominal pain and nausea of one day duration. A CT scan of the abdomen and pelvis revealed multiple heterogenous lesions within the liver, with the largest lesions measured 10.79 × 5.11 cm and 8.0 × 7.12 cm in diameter. Serum α-fetoprotein (AFP) level was 1,131 IU/ml. A diagnosis of HCC was proven histopathologically. Patient refused any treatment and did not seek any herbal or alternative medicine. Six months later, repeated CT scan showed a significant decrease in size of the tumors, and liver function tests and AFP level returned to normal limit. Literature review: Medview was utilized to search for articles that described "spontaneous regression of hepatocellular carcinoma" within the past 30 years. The articles were not limited to English-language. All cases were individually reviewed and mechanisms for regression were analyzed. #### Summary of Results Case report: Twenty four months after the diagnosis, without any treatment, the tumors have regressed to one 2.0 cm and one 1.4 cm diameter lesions, and AFP remained persistently normal. The mechanism for this patient's remission is possibly related to the rapid growth of the tumors. Literature review: Eighty-one reported cases of spontaneous disappearance of HCC were studied. Various mechanisms for spontaneous regression have been suggested including abstinence from alcohol, hormonal influences, withdrawal of agents necessary for tumor growth, ischemia & activation of immune response. #### Conclusions Even though HCC is fatal if untreated, SR is possible and can be stable. Investigating the underlying mechanism of all cases of spontaneous remission of HCC will help to elucidate the etiology of this phenomenon and could provide novel therapy for future treatment of HCC. ### 279 EFFECT OF RITUXIMAB THERAPY ON NK AND T REGULATORY CELLS IN A PATIENT WITH ACQUIRED HEMOPHILIA A R. Kruse-Jarres, F. Ganapamo, C. Leissinger *Tulane, New Orleans, LA*. #### Purpose of Study An 18 year old African-American woman who presented with peri- and post-operatively excessive bleeding following an appendectomy. She was diagnosed with a low titer acquired factor VIII inhibitor (antibody to factor VIII) and was treated with high doses (6000 units/hour) of factor VIII concentrate during the entire period of a complicated hospital course. On this regimen, she had good hemostatic control with normal range factor VIII levels, but this attempt of immune tolerance therapy (ITI) did not completely eliminate the inhibitor. Therefore, treatment with rituximab was initiated. Subsets of immune cells were studied. #### Methods Used During the course of the rituximab regimen, blood samples were collected immediately before the patient received each of four infusions of rituximab (on day 0, 26, 36 and 42). Peripheral blood mononuclear cells (PBMC) were isolated and multi-parameter flow cytometry analysis was performed. Fluorochrome-conjugated monoclonal antibodies specific for human cell markers were used. #### Summary of Results The factor VIII inhibitor disappeared after 4 doses of rituximab and factor VIII rose to a normal level. At day 0 the absolute count of CD19 + cells was 177 cells per milliliter (ml), on day 26 this value drop to 4.1 cells per ml, 87 cells per ml at day 36 and 1.8 cell per ml at day 42. Furthermore, at day zero the absolute number of NK cells (CD56 + CD16+) decrease from 488 cells per ml to 313 cells per ml at day 26, 234 cells per ml at day 36 and 149 cells per ml at day 42. Similarly, at day zero the proportion of T regulatory cells defined as lymphocytes from the CD4 + CD25 + CD127 + low sub populations that are CD45RA- and Foxp3 + was 55.3%. This proportion decreases to 43.1% at day 26, 40.2% at day 26 and 39.7% at day 42. #### Conclusions These results suggested that in this case, well beyond the expected B-cell depletion by rituximab, anti-CD20 therapy has a negative effect on NK cell absolute number and T regulatory cell proportion. ### 280 A TWO YEAR RETROSPECTIVE REVIEW OF THE PRESENTATION OF ANTERIOR MEDIASTINAL MASSES AND THE CONSEQUENCES OF DELAY IN THEIR DIAGNOSIS B. Watkins, A. Mian, S. Siddiqui *Arkansas Children's Hospital, Little Rock, AR*. #### Purpose of Study The purpose of this retrospective analysis is to present case studies on the initial presentation of patients with anterior mediastinal masses, the studies performed to confirm diagnosis and challenges posed to anesthesia with respect to airway management. #### Methods Used Retrospective analysis of fifteen patients, presenting with anterior mediastinal masses, length of time from onset of clinical symptoms to diagnosis of underlying malignancy and the risks they pose when requiring general anesthesia to complete appropriate diagnostic studies. #### Summary of Results Over last 2 years, 15 patients presented with anterior mediastinal mass to our institution. Of these, 10 patients were diagnosed with Hodgkin's Lympoma, 3 with Acute Lymphoblastic Leukemia and 2 with T-Cell Lymphoma. Prior to confirmation of underlying disease, all these patients received outpatient medications including broad spectrum antibiotics and bronchodilators Of this cohort, four patients did not have chest x-rays earlier during their illness (group-1). All of these patients in this sub-group, were found to have pericardial effusions at time of diagnosis, including two patients who had cardiac tamponade. Of the second group of patients (group-2), who got x-rays chest earlier in their illness, only one patient had pericardial effusion at the time of presentation to our institution. The median time of obtaining x-ray chest was 3 weeks from the time of onset of symptoms (range 1-6 weeks) among patients in group-1 and 10 weeks (range 8-32 weeks) among patients in group-2. #### Conclusions Delay in chest X-ray performed by Primary Care Physician in patients with new onset cough in association with other B-symptoms was indicative of a worsening clinical presentation at time of diagnosis with increased morbidity and increased challenges for anesthesia with airway management and resultant increase in length of hospital stay. ## **Infectious Diseases I Concurrent Session** 2:00 PM Friday, February 13, 2009 ### 281 SERUM VITAMIN D LEVELS IN BURN PATIENTS E. Calderon1, C. Yongkuma1, J. Vande Waa1, K. Frye2, A. Luterman2 * 1University of South Alabama, Mobile, AL and 2University of South Alabama, Mobile, AL* #### Purpose of Study Vitamin D has been shown to participate in immune system homeostasis. Burn patients' prolonged stay in the Burn Intensive Care Unit (BICU) -resulting in low exposure to sunlight- may decrease the rate of Vitamin D synthesis in the skin. In addition, burn patients have high serum levels of glucocorticoids and cytokines, factors associated with decreased synthesis of Vitamin D. Decreased levels of Vitamin D may play a role in burn patients' susceptibility and response to infection. We evaluated the initial status and course of vitamin D levels in adult burn patients admitted to the BICU, University of South Alabama Medical Center (USAMC). #### Methods Used This is a retrospective case series. All patients admitted to the USAMC BICU starting May 1, 2008, for whom vitamin D levels were measured within 8 days of admission, were eligible for inclusion. The initial status and course of serum vitamin levels throughout the first four weeks in BICU were recorded. All patients received clinical nutrition, including vitamin and mineral supplements. #### Summary of Results A total of 25 patients (70% male, 80% Caucasian, average 24% total body surface area burned) were included. At admission, 64% of patients (n = 16) showed low serum vitamin D levels (<20 ng/ml). Measured serum Vitamin D levels at two, three and four weeks were available for 13, 7 and 5 patients respectively. Overall, 69% (n = 9), 71% (n = 5) and 60% (n = 3) of those patients had persistent low levels of Vitamin D. There were 15% (n = 2) and 14% (n = 1) of patients with >20 ng/ml of serum Vitamin D at admission who showed decreased levels at two and three weeks. Fifteen percent (n = 2), 14% (n = 1) and 2 (40%) of patients with low initial levels of vitamin D attained levels of >20 ng/ml at 2, 3 and 4 weeks respectively. #### Conclusions Close to two thirds of patients (64%) had low levels of Vitamin D at the time of admission to BICU, and only 20% showed mild increase of serum vitamin D during their stay. These data suggest that vitamin D status should be evaluated initially, tracked and manipulated therapeutically in severely burned patients. Appropriate management of Vitamin D deficiency in severely burn patients may impact the patient's response to infections. ### 282 DISCREPANCIES AMONG RAPID SCREENING, CULTURE, AND PCR FOR RSV AND INFLUENZA M.K. Torres1, M. Broussard2, P.F. Bass2 * 1Louisiana State University @ Shreveport, Shreveport, LA and 2Louisiana State University Health Sciences Center- Shreveport, Shreveport, LA*. #### Purpose of Study 1) Determine trends between discrepancies of the laboratory results of EIA, culture, and PCR assays. 2) Determine which combination is best for RSV and Influenza diagnostic testing. #### Methods Used A convenient sample of patients screened for RSV and Influenza during the 2007-2008 influenza season was evaluated for this study. All lab results were used to calculate assay sensitivity, specificity, PPV, and NPV. The pediatric patients were grouped according to lab results and compared to one another based on several factors including: length of hospitalization, critical threshold values, severity of sickness, duration of symptoms prior to seeking medical treatment, etc. Non-parametric methods were used to determine statistical significance. #### Summary of Results PCR performed better than EIA with 100% sensitivities for both influenza A and B. However, both EIA and PCR assays performed poorly for RSV detection. Additional testing is desired to increase the sample size to obtain more definitive statistical results. Also, the difference in critical threshold values between patients with all three tests positive for influenza A versus those with a positive PCR only were determined to be statistically significant. #### Conclusions This study is crucial for the proper treatment of the patient and prevention of disease spreading. The most significant trend among the three diagnostic tests in regards to influenza A was the difference in Ct values. Individuals positive for all three tests had higher viral loads than those with influenza A positive by PCR only. Similar findings were also observed for patients with influenza B, however, due to the limited sample size, statistical significance is not reached. According to the calculated sensitivities, the PCR assay performed better than rapid EIA for both influenza strains. Based on the raw data, it can be inferred that the PCR assay performed better independent of the viral load and duration of illness prior to diagnostic testing. Unfortunately, both PCR and EIA performed poorly with regards to RSV detection. The limited sample size restricted the results of this study. Increasing the sample size for future studies could statistically support or reject the trends demonstrated by the raw data. ### 283 DAPTOMYCIN IS SUPERIOR TO PENICILLIN FOR TREATMENT OF MURINE SOFT TISSUE INFECTIONS CAUSED BY GROUP A STREPTOCOCCI (STREPTOCOCCUS PYOGENES) A. Rye1,2,4, R. Kudumula1,2,3, A. Talati1,2,3, E.A. Meals2, K. English1,2 * 1Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, TN; 2University of Tennessee Health Science Center, Memphis, TN; 3University of Tennessee Health Science Center, Memphis, TN and 4University of South Carolina School of Medicine, Columbia, SC*. #### Purpose of Study Penicillin (PEN) is the time-honored therapy for infections caused by Streptococcus pyogenes (group A streptococcus, GAS). However, PEN alone is not considered adequate therapy for severe GAS soft tissue infections because of the "Eagle Effect" (failure of PEN but not clindamycin (CLI) in severe soft tissue infection in animal models). It is not known whether antibiotics other than clindamycin are also superior to beta-lactams for treatment of severe GAS soft tissue infections. Daptomycin (DAP) is a novel cyclic lipopeptide antibiotic active against gram-positive organisms that is bactericidal but does not appear to trigger rapid bacterial lysis. We hypothesized that DAP would be superior to PEN for treatment of severe GAS soft tissue infections in mice. #### Methods Used We injected groups of 12 SKH1-Charles River hairless (immunocompetent) mice in the right upper thigh muscle with 1x10∧8 -1.5 × 10∧9 cfu of an M3T1 clinical strain of GAS. We initiated antibiotic treatment (either DAP or PEN) at either 18 hours or 40 hours after bacterial inoculation with 1.5 × 10∧9 and 10∧8 cfu respectively. All animals were observed daily, and lesion size and character were monitored. #### Summary of Results Mice injected with either 10∧8 or 1.5 × 10∧9 GAS consistently developed soft tissue infections; lesions were more extensive and more necrotic in mice given the higher inoculum. Lesion volume in DAP-treated animals was consistently less than that in the PEN-treated animals: 36% less in the animals inoculated with 10∧8 organisms and 64% in the mice inoculated with 1.5 × 10∧9 organisms. Lesions in the DAP treated animals were also much less necrotic in appearance. #### Conclusions We found that mice infected with an M3T1 strain of GAS and treated with DAP developed smaller, less severe soft tissue lesions compared to mice treated with PEN. We conclude that daptomycin deserves additional study as potential therapy for severe GAS soft tissue infections. ### 284 IMMUNIZATION WITH A MULTIVALENT M PROTEIN-BASED VACCINE AGAINST STREPTOCOCCUS PYOGENES PROTECTS AGAINST EXPERIMENTAL GAS SOFT TISSUE INFECTION IN MICE A. Rye1,2,6, R. Kudumula1,2,3, E.A. Meals2, A. Talati1,2,3, J.B. Dale4,5, K. English1,2 * 1Le Bonheur Children's Medical Center, Memphis, TN; 2University of Tennessee Health Science Center, Memphis, TN; 3University of Tennessee Health Science Center, Memphis, TN; 4University of Tennessee Health Science Center, Memphis, TN; 5VA Medical Center, Memphis, TN and 6University of South Carolina School of Medicine, Columbia, SC*. #### Purpose of Study Development of a group A streptococcal (GAS) vaccine is a public health priority. A multivalent GAS vaccine composed of a recombinant fusion protein containing type-specific amino-terminal fragments of six GAS serotypes (M types 1,3,5,6,19, and 24) was recently shown to be safe and immunogenic in adults. It is not known whether this vaccine could provide protection against GAS soft tissue infections such as necrotizing fasciitis. Objective: To determine whether a hexavalent M protein-based vaccine against GAS reduces the severity of soft tissue infections in a murine model of GAS myositis. #### Methods Used We first developed a model of GAS myositis in immunocompetent hairless mice inoculated intramuscularly with an M3T1 strain of GAS. Then we immunized 31 mice × 4 (Day 0, Day 21, Day 133 and Day 147) in the left thigh muscle with either 50 μg alum alone (N = 16) or 50 μg alum + 30 μg of the hexavalent GAS vaccine (n = 15). Subsequently, the animals were challenged with approximately 1-5 × 10(8) bacteria by inoculation in the right thigh muscle. After inoculation, animals were observed and lesions were scored using a severity scale (0 = no swelling or lesion; 1 = swelling only; 2 = swelling and skin discoloration; 3 = skin breakdown/ulcer formation; 4 = necrotic ulcer). #### Summary of Results Mice immunized with the hexavalent GAS vaccine developed less severe lesions than the control mice immunized with alum alone (mean lesion severity score 2.25 at 72h in alum group vs. 0.93 in the immunized group). 81% (13/16) of the mice in the control group developed lesion severities of 2 or greater, compared with only 27% (4/15) of the animals immunized with the GAS vaccine (*P* = 0.014 by chi square test). #### Conclusions Our data indicate that a hexavalent M-protein based GAS vaccine provides substantial protection against GAS soft tissue infection in a mouse model of GAS myositis. ### 285 COMPARISON OF 3 VERSUS 4 DRUGS AS INITIAL HAART: UNIVERSITY OF KENTUCKY EXPERIENCE FROM 1998 M.A. Jhaveri1, H. Bush1, R.N. Greenberg2, S.R. Browning1 * 1University of Kentucky, Lexngton, KY and 2University Of Kentucky Medical School and the Lexington VA Medical Center, Lexngton, KY* #### Purpose of Study The results of ACTG A5095, a randomized, double-blind, placebo controlled study comparing 2 NRTIs + an NNRTI vs. 3 NRTIs + an NNRTI as initial HARRT showed no advantage to the 4-drug regimen. We asked the same question but compared 3-drug vs. 4-drug regimens with or without the use of a PI. #### Methods Used This is a single clinical retrospective cohort study that included all new clients over 18 years from 1998-2007 who were HAART-naive. Data was collected from the subject's first year of HAART and included demographics, viral load, CD4 count, HAART agents and reason for failure (Viral load ≥400/ml after first year of HAART). Genotyping of subject's virus was usually not done prior to HAART. Success was defined as viral load <400/ml after first year of therapy. Analysis used chi-square for categorical variables and T-test for continuous variables. Multiple logistic regressions were performed controlling for various factors. SAS version 9.1 was used. #### Summary of Results 190 subjects were available for analysis with 168 (88%) attaining a viral load <400 copies/ml at the end of one year of HAART; 111 of 129 (86%) that used 3-drugs succeeded and 57 of 61 (93%) that used 4-drugs succeeded (*P* = 0.13). 60 of 72 (83%) who used a PI succeeded vs. 108 of 118 (92%) who did not use a PI succeeded (*P* = 0.08). Controlling for baseline viral load, there was no difference in outcome or percentage change in CD4 counts whether 3- or 4-drugs were used or if a PI were used. Multiple logistic regression analysis did not identify any significant variables for a successful outcome. Failures were due to drug intolerance (50%), non-adherence (45%), and drug allergy (5%). #### Conclusions These results support the current guidelines. ### 286 DYSLIPIDEMIAS IN HIV-INFECTED CHILDREN AND ADOLESCENTS RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY M. Mancao, A. Abesamis *University of South Alabama College of Medicine, Mobile, AL* #### Purpose of Study To investigate the prevalence of hypercholesterolemia and hypertriglyceridemia in patients seen at the University of South Alabama Family Specialty Clinic (USAFSC) from January 2006 through December 2007 and to identify risk factors associated with the development of metabolic changes. #### Methods Used A retrospective chart analysis was performed on infants, children, and adolescents perinatally infected with HIV who were currently on HAART; serum lipid values were obtained and collated. Demographic data was obtained and the Fisher Exact test ws utilized to determine statistical significance of data. #### Summary of Results There were 20 HIV-infected children and adolescents included in the 2-year study period. There were 8 males and 12 females with a median age of 10.5 years among the male patients and 12.5 years among female patients. The mean basal metabolic index (BMI) was 20.2 (range of 14.89 to 31.42). The antiretroviral medications were as follows: 17 patients were on protease inhibitor drug combination while 3 patients were on non-nucleoside reverse transcriptase inhibitor drug combination. There were 8 (40%) patients with elevated cholesterol levels at the end of the study period while 5 (25%) patients had elevated triglyceride levels also at the end of the study period. When comparisons were made among patients with normal and elevated lipid levels in association with gender, BMI, and antiretroviral drug therapy, there was no statistical difference. #### Conclusions In our study population, increased serum levels of cholesterol and triglycerides were independent of gender, BMI, and antiretroviral drug regimen. The study limitations included: retrospective study, small sample size, and differences in duration of HAART use. ### 287 OUTCOMES OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS IN ERA OF HAART L. Cverenkarova, J.A. Vande Waa, W.K. Green, C.M. Burke *University of South Alabama, Mobile, AL*. #### Purpose of Study Cryptococcal meningitis remains a common fungal infection in HIV positive patients. We reviewed cases of cryptococcal infection in HIV-1 infected individuals in our clinics and hospitals since the availability of HAART. Patients' characteristics, associated factors and long term outcomes were examined. #### Methods Used A retrospective chart review of patients with cryptococcal meningitis occurring between January of 1997 and July of 2008. #### Summary of Results Records of 46 patients were identified for review from our university hospitals and clinics, including two Ryan White Title III clinics. Most of the patients were admitted more than once (mean 1.89, range 1 - 6 admissions). Thirty seven (80.4%) were male, most were African American. Eleven patients (23.9%) were newly diagnosed with HIV at the time of their cryptococcal meningitis diagnosis. Twenty-one patients (45.7%) were on HAART and OIP, 4 (8.7%) were on OIP at the time of diagnosis. Thirteen of these (52%) were receiving fluconazole. The mean CD4 count was 30.46 (2 - 138) and the mean HIV viral load was 326,788 (550 to 1,300 000). Forty-one patients survived the initial hospitalization. However, there was a 63% all-cause mortality in the follow-up period in this study (20 - 133 months). Most common sequelae reported were neurologic deficits (65.2%), headache (43.5%), visual problems (17.4%) and hearing problems (13%). Seventeen patient (37%) have survived and records were available for follow-up. All patients were provided appropriate HAART, antifungal therapy and OIP. Only 2 out of the 17 patients (11.8%) have achieved a follow-up CD4 count above 200 (in 26 and 38 months post primary discharge) and only 3 patients (17.6%) achieved a follow-up viral load of less than 1000. Two-thirds of these patients were assessed to be non-adherent to HAART and OIP. Fifty percent of these patients have a reported alcohol abuse, 48% have reported illicit drug use and 52% reported polysubstance abuse. #### Conclusions Despite the availability of HAART, mortality due to Cryptococcus neoformans remains strikingly high. Adherence to antiretroviral medications appears to be a major problem. We need to improve our efforts in adherence and polysubstance abuse counseling. ### 288 MORTALITY AND RESOURCE UTILIZATION IN HOSPITILIZED HIV PATIENTS WITH ACUTE KIDNEY INJURY R. Canada1, B. Abbasi1, K. Huch1,2 * 1University of Tennessee Health Science Center, Memphis, TN and 2VAMC, Memphis, TN*. #### Purpose of Study Kidney disease, including acute kidney injury (AKI), is increasingly being recognized as a complication of HIV or its therapy. Although it is known that AKI is associated with increased mortality in HIV disease, little is known about resource utilization in HIV patients with AKI. Using national administrative data, we sought to describe the demographic characteristics of hospitalized HIV patients with and without AKI and to determine how the diagnosis of AKI impacted length of stay, hospital mortality, and discharge disposition. #### Methods Used Data from the National Hospital Discharge Survey (NHDS) were used. The NHDS is a nationally representative sample of discharges from nonfederal acute care hospitals in the United States. Cases of acute kidney injury (acute renal failure) in patients with HIV were identified using international Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) from 1996 to 2004. Demographic data were collected in hospitalized HIV patients with and without AKI. Main outcome measures were hospital length of stay (LOS) and discharge disposition including death. #### Summary of Results Review of discharge data of patients with HIV from 1996-2004 revealed a projected 1,591,795 hospitalizations with 60,606 (3.8%) of these identified as having AKI. The median age for HIV patients was 40 for those without AKI was 44 for those with AKI. (*P* = < 0.001). AKI was identified more often in blacks and in men and was associated with a prolongation of the median LOS by 4 days (*P* = < 0.001). Kaplan-Meier analysis also demonstrated prolongation of the LOS in HIV patients with AKI and, in addition, confirmed that AKI requiring dialysis was associated with longer LOS than AKI without dialysis. Using multivariate logistic regression, we found that AKI was associated with an adjusted odds ratio of 5.61 for hospital mortality and an odds ratio of 2.952 for discharge to a short or long term care facility. #### Conclusions The presence of a diagnosis code for AKI in hospitalized HIV patients is associated with increased intra-hospital mortality and increased resource utilization both during and after hospitalization. The requirement for dialysis augments this resource utilization. ## **Medical Education and Medical Ethics Concurrent Session** 2:00 PM Friday, February 13, 2009 ### 289 INTERPRETING DNR ORDERS: THE NURSING PERSPECTIVE K. Combs1, A. Hunter1, K. Murphy1, K. Deep2, J. Wilson3 * 1University of Kentucky, Lexington, KY; 2University of Kentucky, Lexington, KY and 3University of Kentucky, Lexington, KY* #### Purpose of Study Healthcare providers may have different opinions about the appropriate level of care for patients with a do-not-resuscitate (DNR) order. These beliefs can cause disagreement among members of the care team. #### Methods Used We surveyed adult acute care nurses about perceived appropriateness of treatments provided to patients with a DNR order. Nurses rated 12 therapeutic interventions on an 4-point Likert scale. Interventions included IV fluids, ICU transfers, and mechanical ventilation. Respondents were asked to describe a situation where there were differences between healthcare providers about appropriate treatment for a patient. Data was analyzed using SAS with descriptive statistics and correlation matrices. Two independent raters performed content analysis of the open response data via an iterative process to develop themes. #### Summary of Results 113 nurses completed the survey for a response rate of 40%. The sample included 58% critical care nurses, with a mean of 9.9 ± 9.6 years of experience. The majority of respondents felt that it was probably or very appropriate for patients with DNR orders to receive IV fluids (92%) and tube feeding (81%). Only half of respondents felt that transfer to the ICU was appropriate. The treatment modalities rated least appropriate were elective mechanical ventilation (36%) and elective cardioversion (39%). Nurses with more years of experience were less likely to rate tube feeding (-0.38) or to transfer to the ICU (-0.43) as appropriate (*P* < 0.01). The open-response question was answered by 53 respondents. Disagreements about care usually occurred with physicians (23) most often when the plan included invasive treatments the nurse felt were inappropriate (17). Nine situations involved physicians pursuing more invasive care than the patient or family wanted. We identified several etiologies for these disagreements including the perceived balance of benefit versus burden of treatment, physician inexperience, and resource use. #### Conclusions Nurses have widely varying beliefs on what treatments are appropriate for a patient with a DNR order. They experience disagreements with physicians about appropriate care for patients near the end of life, often out of concern for the burdens placed on the patient and family. ### 290 UNCOVERING THE POSITIVE INFLUENCES OF THE HIDDEN CURRICULUM M. Disselkamp1, E. Erlandson1, C. Hustedde2, D. Rudy3 * 1University of Kentucky, Lexington, KY; 2University of Kentucky, Lexington, KY and 3University of Kentucky, Lexington, KY* #### Purpose of Study It is well known that much of medical student learning is accomplished through observation and imitation of clinical role models, often referred to as the hidden curriculum. Students learn both positive and negative behaviors in their learning environment. Instead of focusing on the problems with this system, we sought to identify positive experiences during clinical clerkships. By defining the contributing themes, factors, and personal characteristics of these positive encounters we hope to increase their frequency and build upon the current success of the informal curriculum. #### Methods Used Twenty third-year medical students at were interviewed using the technique of Appreciative Inquiry. AI uses interviews to gather information about positive experiences. Students were asked to describe an experience where they witnessed or participated in excellent patient care and to identify persons and their characteristics that contributed to the experience. Transcripts of the interviews were analyzed for thematic categories by two reviewers in an iterative process. Responses were then coded for the presence or absence of the themes. Discrepancies were resolved via consensus. #### Summary of Results Seven accounts (37%) described experiences where empathy in the patient encounter was the underlying focus. Six stories (32%) concentrated on completeness of patient care, five (26%) cited commitment of spending time, and one (5%) described the importance of efficiency in management of emergent care. Contributing personal attributes were greatly dominated by compassion and humanistic attitude, identified in 53% and 37% accounts respectively. Lastly, one student was unable to recount an excellent patient care experience stating everything was "standard of care." #### Conclusions The majority of medical students in this study experienced excellent patient care as part of their hidden curriculum. These encounters revealed compassion, empathy, and humanism along with an unhurried, all-inclusive nature of care. Efforts should be made to identify, acknowledge, and reward persons exhibiting such traits as role models. Such a system would support the continuation of such encounters and foster these attributes to become the standard of care and medical education. ### 291 PEDIATRIC RESIDENTS' NEED FOR TRAINING IN DELIVERING A DIAGNOSIS OF DOWN SYNDROME L. Campbell, J. Ferguson, H. Kleinert, C. Lunney *Univ of KY, Lexington, KY* #### Purpose of Study This study is directed towards the need for improved medical information and support to families as they receive an initial diagnosis of Down syndrome (DS). Using a Web tutorial that integrated prenatal and postnatal information using virtual patient scenarios, the study assessed, with pre and post tests, pediatrics residents' cognitive knowledge and their comfort in delivering a diagnosis of DS. It also measured residents' perception of need for this training. #### Methods Used A team of physicians, parents, and educational specialists integrated previously designed modules into a Web-based interactive tutorial that asked resident physicians to read and view virtual patient-doctor sessions, and provide their own responses to situations related to DS diagnoses both in utero and at the time of birth. The research tested knowledge and attitude changes, assessed the effectiveness of this tutorial as a pedagogical tool, and measured residents' own reactions to the tool as a part of their curricula. Subjects included 88 pediatrics residents from 10 medical schools. #### Summary of Results The study yielded positive and significant improvement in knowledge (Pre-test Mean = 8.18, Post-test Mean = 12.00; *P* < 0.01) and level of comfort (Pre-test Comfort Mean = 23.13, Post-test Comfort Mean = 17.21; *P* < 0.01) changes among the residents. In addition, across all pediatric resident groups (by year, gender, and ethnic identification, performance on the knowledge test, and performance on the comfort scale), residents strongly agreed that this type of training was needed for themselves, for other residents, for practicing physicians, and for other medical professionals (*P* < 0.03). Second year residents were particularly emphatic that the training was needed (*P* < 0.02). #### Conclusions Teaching pediatricians to impart accurate and balanced information about DS and supportive communication can be achieved, in part, through training with the [www.brighter-tomorrows.org](http://www.brighter-tomorrows.org). Residents indicated that this training is important and their regular curricula do not offer similar instruction. From a broader perspective, this effectiveness study suggests the potential applications of these communication strategies not only to families who have a child with DS, but also to those with other life-altering illnesses and disabilities. ### 292 USE OF ADVANCE DIRECTIVES: IDENTIFYING PREDICTORS C.B. Stowe, E.G. Hill, W.P. Moran *MUSC, Charleston, SC* #### Purpose of Study Advance directive use remains low in the United States despite educational and legislative intervention. Experts are now charging the medical community to take responsibility for the use and implementation of advance directives. The first step in this process involves improving our understanding of those patients who already use such documents. The purpose of this study was to use a national database to examine associations between patients' social and health characteristics and their use of advance directives. #### Methods Used We used the 2004 National Nursing Home Survey, a complex sample survey which includes demographic and health information about US nursing home patients, to compare subjects with and without advance directives. We performed univariate analysis to compare variables between the two groups and multiple logistic regression analysis to identify predictors of advance directive use while controlling for demographic covariables. #### Summary of Results There were 13,399 nursing home patients used for data analysis; 9,050 (68%) had an advance directive. In regression analysis, race was significantly associated with advance directive use. Black race decreased the odds of having advance directives (odds ratio [OR] 0.27, 95% confidence intervals [CI] 0.22, 0.32, *P* < 0.001) as did other (OR 0.47, 95% CI 0.36, 0.60, *P* < 0.001). Male gender also significantly decreased the likelihood of having an advance directive, carrying an OR of 0.81 (95% CI 0.72, 0.92). Surprisingly, one year mortality rates as predicted by the Charlson Index were not significantly associated with use of advance directives (*P* = 0.16). #### Conclusions Patients who are nonwhite and male are least likely to use advance directives. We speculate that there are underlying cultural and religious differences also embedded in these decisions. Further research is needed to determine why these patients do not use advance directives. ### 293 IMPROVING TRAINEE PERFORMANCE OF THE NEWBORN PHYSICAL EXAMINATION J.A. Petershack1, A.K. Gong1, M.M. Vasquez1, J.H. Littlefield2, M. Manwell-Jackson2 * 1UTHSCSA, San Antonio, TX and 2UTHSCSA, San Antonio, TX* #### Purpose of Study The newborn physical examination is unique in its scope and challenging in its execution. Preliminary work in developing a performance assessment checklist for the newborn physical revealed a need to improve teaching skills. To this end, we created a 20 minute "teach the teacher" intervention for residents in teaching medical students the newborn physical exam. Our goal was to improve performance of both medical students and residents by increasing resident awareness of teaching techniques and areas for improvement. #### Methods Used IRB approval was obtained. A 20 minute case-based curriculum outlining teaching methods and areas for improvement of the newborn physical exam was discussed with residents at the beginning of their rotation in the newborn nursery. A validated checklist was used by neonatology faculty to directly observe trainees. Faculty were calibrated and inter-rater reliability was established. Two-tailed independent t-tests were used to compare the mean number of checklist items performed appropriately by three levels of trainees before and after formal training. #### Summary of Results Improvements were seen in each group observed: 3rd year medical students, 1st year Pediatric Residents and 1st year Family Practice Residents during their newborn nursery rotation. Baseline data from 85 medical students showed satisfactory performance of 20 of 31 physical exam items. This improved to an average of 25 /31 items correctly performed by 65 medical students assessed after training. 18 pediatric residents assessed prior to the intervention performed 24/31 items well, this increased to 28/31 items after the intervention. Family Practice residents, who spend fewer hours than our Pediatric residents do in the newborn nursery likewise improved from 23/31 items correct prior to the intervention to 27/31 following the intervention. All t-tests were significant between groups to *P*< 0.01. #### Conclusions Newborn physical examination skills can be improved significantly with a relatively simple intervention as measured by a direct observation checklist. A general awareness of the importance of performance of the physical examination and the effects of having a teaching skills program in place are potential contributors to the effects as well. ### 294 USING COGNITIVE MAPPING TO IDENTIFY FACULTY PERSPECTIVES FOR SUCCESSFUL WARD ATTENDING ROUNDS A.H. Salanitro1,2, A. Castiglioni1,2, L.L. Willett2, R.M. Shewchuk2, H. Qu2, G.R. Heudebert1,2, R.M. Centor1,2 * 1Birmingham VAMC, Birmingham, AL and 2University of Alabama at Birmingham, Birmingham, AL* #### Purpose of Study In prior work, housestaff identified factors which contributed to successful ward attending rounds. Less is known about faculty perception of successful rounds; therefore, we sought to understand the conceptual framework of faculty by: 1) identifying factors faculty felt were similar and most important for successful rounds, and 2) create a cognitive map representing faculty perspective on dimensions that contribute to successful rounds. #### Methods Used From multi-institutional nominal group technique sessions, housestaff previously identified 30 factors contributing to successful rounds. For the card sorting activity, factors transcribed onto index cards were mailed to academic faculty who had attended the 2008 Southern Regional Society of General Internal Medicine meeting. Faculty grouped factors by similarity of ideas then ranked each factor's importance in contributing to successful rounds (Likert scale, 1 = least important, 5 = most important). We used multdimensional scaling (MDS) and hierarchical cluster analysis to create a cognitive map. #### Summary of Results Of those recruited, 36 (46%) faculty participated: 8% were instructors, 47% assistant professors, 25% associate professors, 14% full professors, of equal gender mix. Nearly all respondents (94%) endorsed the work-teaching style of rounds at their institution. We observed 6 clusters of related factors: 1) learning climate (mean 4.30, SD 0.45), 2) clinical rationale (4.15, 0.38), 3) respect (3.84, 0.71), 4) managerial skills (3.73, 0.47), 5) teaching style/content (3.71, 0.49), and 6) expectations (3.13, 0.63). We plotted the clusters on a cognitive map, with the x-axis describing attending attributes (interpersonal and professional skills) and the y-axis describing externalities affecting rounds (time, management, and organization). #### Conclusions Faculty recognized similar factors that contribute to successful rounds, and endorsed learning climate and clinical rationale as the dominant areas for achieving success. The cognitive map identified attending attributes and external factors related to management as the two dimensions defining the clusters. Future studies will investigate how housestaff conceptualize and map their factors of successful ward attending rounds. ### 295 TEACHING CORE COMPETENCIES: A HOSPITAL-WIDE MORBIDITY/MORTALITY & IMPROVEMENT CONFERENCE C. Wiggleton1, P. Johnston1, D.H. Arnold1, P.G. Throop2, J.K. Deshpande1,2, B.S. Carter1 * 1Vanderbilt University Medical Center, Nashville, TN and 2Monroe Carell, Jr. Childrens Hospital at Vanderbilt, Nashville, TN* #### Purpose of Study The ACGME core competencies (CC) include addressing resident practice based learning and improvement, systems based practice, interpersonal/communications skills, and professionalism. Training programs need effective mechanisms to teach these CC. We sought to assess the ability of a hospital-wide Morbidity/Mortality and Improvement (MM&I) conference to address CC in resident education. #### Methods Used A hospital-wide MM&I conference was developed and held 32 times over the past 44 months. Through a task force of nurses, resident & attending physicians, and quality improvement staff, cases were selected and presented in a monthly multidisciplinary forum. Contributing factors to adverse events were identified using the Ichikawa cause: effect diagram. Action items were identified and tracked for completion. Conference attendance was monitored. Evaluation of conferences was directed at individual participants' ability to use the conference to improve systems-based practice in their own work. #### Summary of Results Mean monthly participants numbered 88; 50% completed evaluations. Cases emanated from all areas (ED, ICU, OR, wards & clinics), and addressed unexpected death, unplanned intubation or readmission to ICU, delay in diagnosis or care, medication error, prolonged medical care in a setting of poor prognosis, "near miss" situations, and success stories. Affirmative responses (88-100%) indicated learning improved practice and was applicable, group interaction was good and case presentation/discussion was non-threatening/non-accusatory [e.g maintained professionalism]. Conference helped attendees understand system-based practice and provided opportunity for practice-based learning and improvement. #### Conclusions A structured, system-wide MM&I conference is an effective way to engage the healthcare team in discussion and analysis of adverse outcomes while focusing on system-wide improvements in patient care and safety. Non-judgmental process-oriented case discussion helps overcome individual fear of accusation and promotes identification of system failures and potential improvements. Residents report CC were met in a case-based and effective learning environment. ### 296 ETHICS REVIEW COMMITTEES IN RURAL HOSPITALS E. Jackson, K. Olive *Quillen College of Medicine, Johnson City, TN*. #### Purpose of Study Little information is available regarding the structure of ethics committees in small, rural hospitals. Further, no research has been conducted to observe what impact, if any, the culture of rural settings has on the types of issues with which ethics committees deal. The purpose of this study is to provide a broad overview of ethics committees in small, rural hospitals in East Tennessee. #### Methods Used East Tennessee hospitals located in cities less than 15,000 people were identified. The population threshold was arbitrary and based on the natural stratification patterns of the populations of the area. From this list, eleven hospitals were contacted, and ethics committee representatives from nine of these hospitals were interviewed. A structured interview format was used to address a range of topics. Hospital size ranged from 6 to 230 beds. #### Summary of Results Of the nine hospitals interviewed, all had functional ethics committees. Interview answers were categorized into 1) committee structure; 2) ethical issues faced; and 3) educational initiatives. The most unique trait afforded to small hospital ethics committees was their ability to communicate effectively and efficiently due to their small size, familiarity among staff members, and homogeneity of opinions. This allowed many committees to reduce the number of formal consults made to the entire committee. The religious and social culture of the area subtly impacted the type of issues the committees faced as did the administrative network with which each hospital affiliated. Given the interview format, the answers given by each interviewee was colored by each person's educational background. #### Conclusions Few stereotypes given to the Appalachian region of East Tennessee actually impact the structure and function of the ethics committees within the region. Connection to a larger network provides a larger community of support and supplies an outline for how the committee operates. However, the small size of these hospitals reduces the inefficiency created by the bureaucracy of larger hospitals and enhances communication. Consequently, the number of formal consults handled by the committee is reduced. Ethics committees in rural hospitals are effective and contain a level of organization comparable to that of larger hospitals. ### 297HISPANIC CULTURE AND LANGUAGE FOR THE RESIDENT J. Gerwe *University of Louisville, Louisville, KY* #### Purpose of Study The increase in Spanish speaking patients in our healthcare system is adding to the complexity of the cultural competence required of health professionals. This study compared pediatrics residents' perceptions of their fluency in Spanish, their comfort level with speaking medical Spanish, and their confidence in effectively communicating with Spanish speaking patients before and after completing a series of lessons in practical clinical Spanish and Hispanic culture. #### Methods Used A pretest/posttest design was used with 11 one hour sessions as the intervention. The pretest questionnaire contained 10 items on a 5-point (low to high) Likert scale. The posttest had the same 10 items plus one more 5-point question (N = 14). Pretest and posttest scores were then compared using the Wilcoxon signed rank test. Posttest results of residents who did not take the pretest but had completed the lessons (N = 30) were also analyzed. #### Summary of Results Fourteen residents completed both tests. Cronbach alpha for the nonpiloted study was.85 for the pretest and.75 for the posttest. The posttest average item score was 2.5 ± 0.6 (SD) vs 2.1 ± 0.7 for the pretest (*P* = 0.015). Three of 10 items showed increases: ability to use Spanish phrases in emergencies (2.2 ± 1.0 vs 1.5 ± 0.9); knowledge of Spanish words for body parts (3.1 ± 1.1 vs 2.1 ± 1.1); understanding of Hispanic cultural issues that could affect physician/patient communications (3.1 ± 0.8 vs 2.2 ± 1.1); all *P* ≤ 034. Notably, those taking both tests had higher score items assessing a) awareness and b) understanding of Hispanic cultural items that could affect communications (3.2 ± 1.0 vs 2.5 ± 0.8 and 3.1 ± 0.8 vs 2.4 ± 0.7, respectively; both *P* ≤ 034 [Mann-Whitney U test]). No other items resulted in statistical differences between residents who took only the posttest versus those taking both the pretest and posttest. #### Conclusions The results of this small pilot study of an 11-week curriculum on Hispanic culture and language for pediatrics residents demonstrated benefits in terms of self-assessment of competence. The benefit may be most important in improving effectiveness of communications in emergency care settings. It also seems that the experience of the pretest may have caused residents to gain more from the lessons, specifically in the area of Hispanic culture. Further evaluation and development of this curriculum is warranted. ### 298 SCREEN-BASED SIMULATION PROTOTYPE FOR TEACHING HYPOVOLEMIC SHOCK TO MEDICAL STUDENTS - A SUPPLEMENT TO IN VIVO LABS A. Hilton, V. Kozmenko, V. Rusnak, V. Kiselov, A. Kaye, M. Levitzky, K. McDonough, C.W. Hilton *LSU School of Medicine, New Orleans, LA* #### Purpose of Study Teaching clinical application of various physiologic and pharmacologic concepts is an important part of medical education. Using multimedia-rich screen based simulation allows for providing educational experiences for the medical students that would otherwise require an in vivo approach. #### Methods Used To create a dynamic simulation experiences, we developed new technology that combines two and three dimensional animation and mathematical models of the various physiologic processes. Simulation scenarios such as hypovolemic shock are presented as realistic clinical vignettes. Students can observe or/and intervene in the scenarios. Created using "Poser 7," the 3D animation shows the neuropsychological changes of the virtual patient during the scenario. Quad-screen technology is used to organize the estate of the screen. 3D animation is placed in the upper left screen, while patient's vital signs, pertinent laboratory data, 2D animation of normal and abnormal physiologic processes and user controls are ergonomically distributed across the remaining sectors of the quad screen. Clinical scenarios proceed the through 4 stages of hypovolemic shock. The software prompts the user to summarize observed experience at the end of each level which promotes reflection and provides context and feedback. #### Summary of Results Our preliminary results show that the software realistically simulates CNS, physiologic, biochemical and pharmacologic processes of hypovolemia. For example, during progressive blood loss the patients level of consciousness, hemodynamic, breathing pattern and lactate levels were appropriate for the degree of hypovolemia. #### Conclusions We have developed a screen-based simulation that closely mimics the physiologic and clinical responses seen in hypovolemia experiments. This may allow substitution for some training previously done in vivo. Using 3D animation reinforces basic science principles by introducing clinical context. Presenting the cases in form of realistic clinical vignettes can potentially help students retain basic science knowledge during the clinical rotations. ### 299 SURVEY OF PEDIATRIC RESIDENT ADVOCACY ATTITUDES, PRACTICE AND KNOWLEDGE J. Quigley1, C. Chen2, K. Northrip1 * 1University of Kentucky, Lexington, KY and 2Children's National Medical Center, Washington D.C., DC* #### Purpose of Study To evaluate pediatric resident child advocacy attitudes, practice and knowledge. In 1996, the Pediatric Residency Review Committee added child advocacy to program requirements for residency education. The AdvocacyOnCall.org website was created to increase the knowledge and comfort of residents in regard to patient-level, community-level and legislative advocacy. A pre-, immediate post- and follow-up post-survey method was designed to assess the efficacy of the website. This study describes pre-survey data. #### Methods Used We distributed online pre-surveys to all UKY pediatric, medicine/pediatrics, and triple board residents. They were then required to complete an online educational session using AdvocacyOnCall.org during their pediatric clinic rotation. An immediate post-survey followed. Follow-up post-surveys will be distributed one year after the pre-survey period. The survey included questions designed to gauge resident attitudes, practice and knowledge of advocacy issues. The survey instrument was developed from work done at Johns Hopkins and Children's National Medical Center to evaluate the efficacy of an advocacy code card. Analysis is descriptive. #### Summary of Results Of 45 residents, 58% (n = 26) responded to the pre-survey. See table for selected responses. 85% of respondents agreed lack of training, lack of time and poor awareness of available resources were barriers to advocacy. #### Conclusions The results of this study identify knowledge gaps and a discrepancy between pediatric residents' desire verses perceived ability to be child advocates. This study highlights the need for an advocacy curriculum throughout residency training. View this table: [Table28](/content/57/1/301/T28) ## **Perinatal Medicine I Concurrent Session** 2:00 PM Friday, February 13, 2009 ### 300 FATTY ACID ETHYL ESTERS AS A POTENTIAL BIOMARKER OF IN-UTERO ETHANOL EXPOSURE IN PRETERM GUINEA PIG PLACENTAS S.S. Mohan, T.W. Gauthier, F.L. Harris, L.S. Brown *Emory University, Atlanta, GA*. #### Purpose of Study Detection of the newborn exposed to alcohol in utero is essential to establish early intervention in this high risk population and understand mechanisms of injury. Our lab has found that fetal ethanol (ETOH) exposure caused injury to the developing lung (a process modulated by the presence of the antioxidant glutathione) (GSH). In addition, fetal alcohol exposure predisposed the newborn to infections which can significantly impact morbidity. Previous studies have shown that fatty acid ethyl esters (FAEEs), non-oxidative metabolites of alcohol (particularly linoleic, linolenic, oleic, and arachidonic acid), in meconium are potential biomarkers of fetal alcohol exposure and effect in term newborns. However, the identification of premature newborns exposed to alcohol in utero is lacking. The aim of this study was to evaluate FAEEs in placenta as potential biomarkers of in utero ETOH exposure in the developing guinea pig. #### Methods Used Using our established timed-pregnant guinea pig model of fetal ETOH exposure, twenty guinea pig dams were randomly assigned to 3 different groups (control, ETOH, or ETOH + SAM-e (a GSH donor) in the drinking water). Placentas were evaluated at 55 days gestation (term is 72 days) and analyzed by gas chromatography to determine FAEEs content. Values are presented as mean ± SEM ng FAEEs normalized to placenta protein (measured via fluorescent assay). Statistical analysis was performed via Sigma Stat with *P* ≤ 0.05 considered significant. #### Summary of Results FAEEs were detected in all samples evaluated at 55 days gestation. The sum of the oleic, linolenic, linoleic, and arachidonic acid FAEEs (OLL + AA) was significantly elevated with fetal ETOH exposure compared to control (*P* = 0.043). Maternal SAM-e during ETOH ingestion did not reduce OLL + AA in the placenta compared to ETOH alone (*P* = NS). #### Conclusions In our guinea pig model, the FAEEs OLL + AA were significantly increased in ETOH-exposed placentas. Further studies will determine FAEEs concentrations in ETOH-exposed premature lung. We speculate that FAEEs will serve as potential biomarkers for in utero exposure to alcohol in the at-risk premature newborn. ### 301 EARLY BUBBLE CONTINUOUS POSITIVE AIRWAY PRESSURE WITH TARGETED OXYGEN SATURATION IMPROVES OUTCOMES IN PREMATURE INFANTS V. Kakkilaya, D. Kurepa, D. Johnson, L. John, S. Hussein, H. Ibrahim, G. Caldito, A. Pramanik *LSUHSC, Shreveport, LA* #### Purpose of Study Evaluate the outcome of simultaneous introduction of Bubble CPAP (BCPAP) with targeted SpO2 85-93% in infants ≤32 weeks of gestational age (GA). #### Methods Used Infants ≤32 weeks of GA born between February and August 2008 (study group) were compared to infants born in 2007 (control group). Control group was resuscitated with T-piece resuscitator. Infants ≤29 weeks of GA with respiratory distress were given surfactant and started on SIMV. Variable flow CPAP was used post-extubation. SpO2 was maintained 88-95%. Study group infants <26 weeks of GA and infants ≥26 weeks of GA unresponsive to resuscitation were given surfactant and started on SIMV. Infants ≥26 weeks of GA who responded to resuscitation were transferred to the NICU on CPAP and started on BCPAP 5-6 cm H2O. Infants were given surfactant if FiO2 was >0.40 to maintain SpO2 85-93% or pH<7.20 with PCO2>60 torr or persistent apnea with labored breathing. Intubated infants were aggressively weaned to BCPAP. Wide swings in FiO2 were avoided. Wilcoxon rank sum test compared the groups on numeric variables. Chi-square or Fisher test compared them on categorical variables. They were adjusted for significant differences on confounding factors with multiple logistic regression analysis. #### Summary of Results Study (N = 51) and control group (N = 96) were similar in the use of antenatal steroids, chorioamnionitis, Apgar, birth weight (1020 ± 300 vs 957 ± 307 grams), GA(28.2 ± 2.3 vs 27.6 ± 2.2 weeks), sex, race, sepsis, PDA with exception of increased vaginal delivery in control group (p = 0.006). Study group had significantly lower rates for intubation in the DR (*P* < 0.001), use of early surfactant (*P* = 0.006) and no pneumothorax. Outcomes(image 1). #### Conclusions NICU staff education, early Bubble CPAP use with targeted oxygen saturation along with reduced DR intubation led to significant decrease in number of days on O2, mechanical ventilation, incidence of BPD, ROP and IVH View this table: [Table29](/content/57/1/301/T29) ### 302 HIGH FREQUENCY (HF) VENTILATOR TIDAL VOLUME (TV) DISTRIBUTION TO INHOMOGENEOUS LUNGS IN A NEONATAL TEST LUNG MODEL R. Gillette *Wilford Hall Medical Center, San Antonio, TX* #### Purpose of Study The SensorMedics 3100A HF oscillator is widely used and use of the Bronchotron HF "percussive" ventilator (Percussionaire) for neonatal transport is spreading rapidly. Gas exchange with HF ventilators is believed to depend on frequency (F) times TV squared. The distribution of HF TV between lungs which are inhomogeneous in compliance (C) and resistance (R), and the its dependence on F, is not well studied. #### Methods Used Each HF ventilator was connected to two 3.0 L calibration syringes (Hans Rudolph) used as test lungs with C of 0.07-2.1 ml/cmH2O set by varying their volumes, via a 4.0 mm endotracheal tube, a 15 mm y-connector, and calibrated airway R of 0-250 cmH2O/L/s in line with each lung. TV to each lung and proximal pressure amplitude (PA) were measured with a Florian hot wire anemometer (Acutronic) at various combinations of C, R, F, and PA. #### Summary of Results With bilaterally minimal R, distribution of TV reflected the ratio of C between lungs over a wide range and at several F levels. TV distribution between lungs with equal high R (>200) was nearly equal and minimally dependent on F or degree of C inequality. With highly-inhomogeneous R (>200 unilaterally) there was F-dependence (more equal TV's at lower F) if C was very low bilaterally or with R/C mismatch (high R/high C vs. low R/low C), but if C was high and equal, or lower on the high-R side, TV mostly went to the low-R side, independent of F but with slightly more unequal TV's at more unequal C. With low-moderate, equal to moderately-unequal R, and matching-sided inhomogeneous C, F dependence showed more equal TV distribution at higher F and at more-equal C, as it did when lungs were mismatched for R and C but with moderately inhomogeneous R. Results were similar with both ventilators but reflecting previously noted differences in effective R between them. #### Conclusions Distribution of TV between lungs in this model depended markedly on inhomogeneities of R and C. Patterns of dependence on F varied widely determined by specific combinations of inhomogeneities. Electrical circuit analog theory largely explained the findings. We speculate these results may favor clinical use of higher F in early (low R, inhomogeneous C) premature lung disease and lower F with airway disease (highly-inhomogeneous R plus low C or R/C mismatch). ### 303 EFFECT OF IMPLEMENTING GUIDELINES FOR OXYGEN SATURATION MONITORING ON THE INCIDENCE OF RETINOPATHY OF PREMATURITY (ROP) AND CHRONIC LUNG DISEASE (CLD) M.R. Pabbathi, A.J. Talati, R. Dhanireddy *The University of Tennessee Health Science Center, Memphis, TN* #### Purpose of Study Several retrospective and cohort studies show a decline in ROP with maintaining oxygen saturation in a defined range. The incidence of ROP and severe ROP was higher in our NICU compared to similar centers in Vermont-oxford database, this lead us to implement practice guidelines. The objective of this study was to compare the incidence/severity of ROP in infants <30 weeks EGA, before and after implementation of practice guidelines in our NICU. #### Methods Used A retrospective study was done by patient database review of a level III NICU from 2003 to 2007. Intensive nursing education was started in late 2005 and guidelines were implemented to monitor oxygen saturations in clinical practice in 2006. Prior to 2006, though intended by all physicians, no clear guidelines were available for the nurses or respiratory therapists to maintain oxygen saturations. The new guidelines required for the nurses or respiratory therapists to wean supplemental oxygen based on pulse oximetry; alarms were set at 85-95% and target oxygen saturations at 90-95%. Data regarding number of VLBW admissions, incidence of ROP, Chronic lung disease (CLD) and other outcomes were collected and analyzed by chi-square test. #### Summary of Results The total number of infants admitted in our NICU remained between 1000-1200/year over the period studied. Data for infants <30 wk EGA are in table below. #### Conclusions Our preliminary data confirm the findings of other studies that guidelines and education of nursing staff regarding oxygen saturation monitoring can decrease the incidence of ROP in infants <30 weeks EGA. The incidence of CLD was also reduced by using oxygen monitoring guidelines and education to the nurses, which has not been observed before. View this table: [Table30](/content/57/1/301/T30) ### 304 DEVELOPMENT OF A HOSPITAL-BASED MEDICAL HOME PROGRAM FOR SPECIAL NEEDS CHILDREN: FOLLOW-UP OF NICU GRADUATES WITH COMPLEX BRONCHOPULMONARY DYSPLASIA A. Massey2, A. Breaux1, K. Burns1, M. Bird1, J. Robbins1, P. Casey1, R.E. Lyle1 * 1Univeristy of Arkansas for Medical Sciences, Little Rock, AR and 2Ouachita Baptist University, Arkadelphia, AR* #### Purpose of Study Provision of family-centered, coordinated and continuous care is the foundation for establishment of the medical home. However, medically-complex NICU graduates pose significant challenges to attain this ideal. In 2006, a multidisciplined collaboration at Arkansas Children's Hospital including neonatology and developmental pediatrics, led to the development of a new model of medical home care. This hospital-based program seeks to augment community care by focusing on case management and improved communication, while overseeing the child's general medical, nutritional, developmental and psychosocial needs. A broad-range of special needs children can be referred to this clinic, however, specific targets were high risk NICU graduates. #### Methods Used To enhance continuity, the majority of infants had been discharged by the same neonatologist who provided follow-up with the medical home specialty nurse assigned to this cohort of patients. Routine visits consisted of a thorough medical care plan review by the nurse and physician as well as evaluations by a nutritionist and social worker. Developmental psychologists and speech pathologists were available for testing. Case management by the nurse and physician after the clinic was vital to advancing the care plan. Resource utilization was studied via the hospital's information management system. #### Summary of Results 58 infants with bronchopulmonary dysplasia (BPD) have been enrolled with an average gestational age of 24.8 weeks. All were discharged on oxygen therapy. 30 infants had feeding problems requiring placement of gastrostomy tubes and 22% had severe intraventricular hemorrhage (grade 3 or 4). 12-month pre- and postenrollment periods were examined.79 postenrollment emergency room visits and 110 inpatient admissions were identified. However dramatic and significant reductions in postenrollment mean hospital charges per month were identified ($6248 vs $1992, *P* < 0.001) signifying reduction in disease severity and length of stay. #### Conclusions We conclude that a hospital-based medical home program is effective at providing improved care coordination with a resultant reduction in hospital charges in NICU graduates with complex BPD. ### 305 EFFECT OF MATERNAL WEIGHT ON POSTTERM DELIVERY D.R. Halloran1, Y. Cheng2, A.B. Caughey2 * 1Saint Louis University, St Louis, MO and 2University of California San Francisco, San Francisco, CA* #### Purpose of Study Increasing gestational age beyond term is associated with increased risk of birth injury, meconium aspiration, cesarean delivery, and other complications. To assess the effect of prepregnancy BMI and weight gain on postterm delivery. #### Methods Used This is a retrospective cohort study utilizing birth records linked to hospital discharge data for all term, singleton infants >37 weeks gestation born to Missouri residents (1993-1999), excluding infants born to mothers with diabetes or chronic hypertension or a history of previous cesarean section. The primary outcome was delivery at 42 weeks gestation. Prepregnancy BMI was categorized as follows: normal (referent) (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥30 kg/m2). Maternal weight gain was categorized as more than, less than, or within (referent) the Institute of Medicine (IOM) recommendations which are adjusted for pre-pregnancy weight. #### Summary of Results There were 416,358 births meeting study criteria. 8542 infants (2%) were born at 42 weeks gestation. Multivariable analysis was performed that controlled for maternal ethnicity, age, education, parity, tobacco history, Medicaid status, and infant sex. Being under weight and gaining less than the weight recommended by the IOM decreased the risk of postterm delivery. Being overweight and gaining more than the recommended weight increased the risk of postterm delivery. #### Conclusions Elevated weight gain and elevated prepregnancy weight increase the risk of a postterm delivery while low weight gain and prepregnancy weight decrease the risk of a postterm delivery. While most women do not get preconceptional care, our findings suggest that restricting weight gain to the normal range can reduce the risk of postterm pregnancy. View this table: [Table31](/content/57/1/301/T31) ### 306 NEUTROPENIA AND THROMBOCYTOPENIA IN VERY LOW BIRTH WEIGHT INFANTS OF WOMEN WITH PREECLAMPSIA N. Claudio, L. Garcia, I. Garcia, M. Valcarcel *University of Puerto Rico School of Medicine, San Juan, PR* #### Purpose of Study To describe the clinical course of very low birth (VLBW) infants born to mothers with preeclampsia and determine factors associated to neutropenia and thrombocytopenia. #### Methods Used Data from all VLBW infants admitted to the Neonatal Intensive Care Unit of the University Pediatric Hospital during the years 2005-2007 was reviewed to identify infants born to mothers with preeclampsia. Analysis of the cohort of infants born to mothers with preeclampsia was performed with cases including infants with neutropenia and/or thrombocytopenia during the first week of life and the control group including infants without neutropenia and/or thrombocytopenia. #### Summary of Results Five hundred and sixty seven VLBW infants were admitted to NICU during the study period with 16% of them being born to mothers with preclampsia. No difference in gestational age or birth weight was seen among infants born to mothers with or without preeclampsia. Cesarean section delivery was more common in the preeclampsia group (96% vs 64%, *P* = < 0.01). Analysis of infants born to mothers with preeclampsia showed a mean maternal age of 26 years (14-36). The mean birthweight of the infants was 988 grams (430-1460) and the mean gestational age was 29 weeks (29-36). Neutropenia was present in 24% of the infants born to preeclamptic mothers and thrombocytopenia in 16%. These Infants were of lower birth weight and lower gestational age. Neutropenia was associated to a higher prevalence of positive blood cultures during the first week of life (40% vs 7%, *P* = 0.0013). Thrombocytopenia was associated to lower survival (38% vs 72%, *P* = 0.0198). #### Conclusions VLBW infants born to mothers with preeclampsia who present neutropenia and/or thrombocytopenia are at increased risk of complications and mortality. ### 307 WHY ARE MOTHER CHOOSING "LOS DOS", OR BOTH BREAST AND BOTTLE FEEDING FOR THEIR NEWBORN BABIES? E. Ponce de Souza, A.K. Gong *University of Texas Health Science Center in San Antonio, San Antonio, TX*. #### Purpose of Study To understand the reasons why mothers choose to simultaneously bottle and breastfeed from birth, and to determine whether this choice of early bottle feeding undermines their long-term success at breastfeeding. Our goal is to better support new mothers in making decisions which will not affect their wish to breastfeed. #### Methods Used A prospective study regarding newborn feeding practices and choices was conducted in English and in Spanish. A survey was developed and was distributed to post-partum women who expressed their desire to partially or exclusively breastfeed their babies with a follow-up questionnaire conducted at two and six months to investigate how their feeding practices had evolved. #### Summary of Results Thus far, 180 surveys have been collected, and of those 59 have given a reason for offering mixed feedings to newborns; these fall into eight main categories. 34% of these mothers have cited potential insufficient milk production; 20% are concerned about returning to work; 13% cite reluctance to breastfeed in public; 10% anticipate poor latch or rejection of breast by baby; 7% find bottle feeding "most comfortable"; 5% cite the misconception that while breastfeeding is emotionally more nurturing, formula provides "more vitamins"; 5% cite physical pain associated with breastfeeding; 5% want to leave baby with other caregivers. The majority of the replies (83%) were from Spanish only women and the follow-up survey results are being completed. #### Conclusions Our preliminary results are thus far consistent with the national average. Perception of breast milk as an emotional bonding factor but an inferior source of nutrients for babies despite massive breastfeeding campaigning is surprising and noteworthy. A large proportion of mothers anticipates an inadequate supply of milk, even while still in the hospital, and a significant group of women does not believe that work and breastfeeding are compatible. This suggests that more pointed educational efforts targeting some of the specific categories outlined here before the baby's birth, may yield higher ratios of women deciding to exclusively breastfeed from the beginning. ### 308 COMMUNITY VERSUS ACADEMIC MEDICAL CENTER CARING FOR LATE PRETERM INFANTS N. Ahmed, A. Parish, S. Edell, D. Gillis, J. Bhatia *Medical Collge of Georgia, Augusta, GA* #### Purpose of Study Preterm delivery, especially of the late preterm infant, is increasing in the United States. The purpose of the study is to review and describe the outcome of late preterm infants who were born at a community hospital CH and an academic medical center AMC. #### Methods Used We reviewed the postnatal course of infants of 34-36 weeks gestation cared for in CH or AMC setting. Infants admitted to CH or AMC from 10/04 to 10/07 were identified from hospital medical records. Birthweight, gestational age, length of stay, and diagnoses of hypoglycemia, jaundice, and respiratory distress were recorded. For the AMC, number of infants readmitted after the initial hospitalization and reasons for the same were recorded. There were 138 and 399 patients who met the inclusion criteria admitted to CH and AMC, respectively. Birthweight range was similar for the two settings: 1300-3700 g for the CH and 1270-4390 g for the AMC. #### Summary of Results At the CH 47% of babies were delivered by cesarean section whereas only 37% were at the AMC. Length of stay ranged from 1-21 days for CH and 1-35 days for AMC; average length of stay was 4.5 days for the CH and 4.8 days for the AMC while median length of stay was 3 days for both hospitals. Twelve patients [8%] from the CH required transfer to the AMC. In the AMC, 36 patients [9%] were readmitted within the first 6 weeks of life with the following diagnoses: respiratory distress 11 [30.5%], jaundice requiring treatment 12 [33.3%], poor feeding/failure to gain weight/dehydration 8 [22.2%], ALTE 1 [2.7%], pyloric stenosis 1 [2.7%] and apnea 3 [8.3%]. #### Conclusions Although length of stay was similar, the morbidities were quite different between the two hospitals. Also of concern is the higher C-section rate in the CH. The CH does not rehospitalize patients and although they are more likely to be readmitted to the AMC, our data does not allow this conclusion. Criteria for hospital discharge of late preterm infants need to be reexamined given the readmission rate in the AMC and the incidence of reported morbidities. View this table: [Table32](/content/57/1/301/T32) Incidences of morbidities are summarized in the Table ### 309 UNNECESSARY WORKUP OF ASYMPTOMATIC TERM NEONATES IN THE ERA OF INTRAPARTUM ANTIBIOTIC PROPHYLAXIS FOR GROUP B STREPTOCOCCUS? B. Buckler1, J. Bell2, J. Bartley1, W. Cagle1, N. Ahmed1, S. Bell2, C. Allen2, D. Sutherland3, J. Bhatia1 * 1Medical College of Georgia, Augusta, GA; 2Medical College of Georgia, Augusta, GA and 3Medical College of Georgia, Augusta, GA* #### Purpose of Study The purpose of the study is to examine the medical management of asymptomatic neonates born at term either to mothers who are Group B Streptococcus (GBS) unknown or to mothers who are GBS positive but "inadequately" treated prior to delivery. #### Methods Used The study design was a chart review of mother/baby dyads born at the Medical College of Georgia from January 1, 2005 until September 30, 2007 and cared for in the Newborn Nursery, which is staffed by general pediatricians. The protocol is to obtain a Complete Blood Count with a Differential, a blood culture, and C-reactive protein immediately after birth. Then, based on the results of these lab tests a decision to start antibiotics is made. #### Summary of Results Mother/baby dyads (n = 242) who met the following inclusion criteria were reviewed: term, mother's GBS status unknown or positive, no antibiotics or antibiotics less than 4 hours prior to delivery, and a laboratory evaluation in the newborn nursery. Of these 242 babies 25 (10%) were started on antibiotics. Antibiotic therapy was discontinued after 48 hours on 23 out of the 25 babies that were started on antibiotics, and the other 2 babies received 7 days of antibiotics for signs of clinical sepsis. None of the 242 blood cultures were positive and the C-reactive protein levels were normal. #### Conclusions The 2002 GBS guidelines call for laboratory evaluation for "at-risk" neonates, but the workup of these babies is not only costly, it does not provide any advantage over good old fashioned clinical observation for the evaluation and treatment of early onset GBS sepsis. View this table: [Table33](/content/57/1/301/T33) ### 310 OCCURRENCES OF LATE INFECTION IN THE NEONATAL INTENSIVE CARE UNIT: A 10-YEAR EXPERIENCE A. Abdu1, H.S. Bada1, D.T. Granger1, E. Reynolds1, M. Mendiondo2 * 1College of Medicine University of Kentucky, Lexington, KY and 2College of Public Health University of Kentucky, Lexington, KY* #### Purpose of Study Nosocomial infection (late onset infection) is a common cause of morbidity and mortality in infants admitted to the neonatal intensive care unit (NICU), particularly in those with very low birth weight (VLBW). Our primary objectives were to determine the pattern of infection across years and to determine the predominant etiologic agents for invasive infections by different birth weight. #### Methods Used Using the NICU database for the years 1997 to 2006, we analyzed information from all babies with NICU stay >3 days. Late onset infection was defined as any infection (sepsis, meningitis, urinary tract infection/abscess/cellulitis, necrotizing enterocolitis, or pneumonia) occurring after three days of NICU stay. #### Summary of Results We had a total of 6587 neonates who were admitted to the NICU with length of stay >3 days from 1997-2006, with 56% males and 44% females. 25.2% and 34.7% respectively had BW <1501 g and gestational age <33 weeks. Total number of infants with any type of infection (e.g., sepsis, meningitis, urinary tract infection, pneumonia, or necrotizing enterocolitis) was 1058 (16%) with a total 2077 episodes or occurrences (1.96 episodes/patient), accounting for 14.1 episodes/1000 baby days. Of 2077 total episodes of infections, septicemia accounted for 964 (46.1%), UTI 91 (4.3%), pneumonia 234 (11.1%), meningitis 29 (1.4%), and cellulitis or abcesses 388 (18.5%). Of all episodes of infection, 993 were septicemia/meningitis. Of these septicemia/meningitis episodes, 755 (76%) were due to Gram positive organisms, 158 (15.9%) Gram negative, 60 (6.04%) fungal, and 20 (2.0%) viruses. 53.6% of septicemia/meningitis episodes occurred in babies with BW <1000 g, who comprised 11.8% of the total admissions. 52.1% of episodes were in those <28 weeks' gestation, who comprised 11.2% of admissions. There were only 60 total fungal episodes with 34 diagnosed in those with BW<750 g (56.7%), another 16 in the 751-1000 g BW group. #### Conclusions The predominant etiologic organisms for invasive nosocomial infection in our NICU were the Gram-positive organisms. Less frequent were the Gram-negative organisms. While fungal infection was rare, greater than 80% of fungal episodes occurred in the extremely low birth weight infants ## **Pulmonary and Critical Care Medicine Concurrent Session** 2:00 PM Friday, February 13, 2009 ### 311 ZINC SUPPLEMENTATION IMPROVES SEVERITY OF KLEBSIELLA PNEUMONIAE PNEUMONIA IN THE SETTING OF CHRONIC ALCOHOL INGESTION IN RATS A.J. Mehta, P.C. Joshi, D.M. Guidot *Atlanta VA and Emory University, Atlanta, GA* #### Purpose of Study Alcohol abuse renders individuals susceptible to lung injury and infection, but a complete mechanistic explanation for this observed vulnerability has yet to be elucidated. Studies performed in our laboratory and by other investigators show that there is a significant impairment in the ability of alveolar macrophages from alcohol-fed rats to phagocytose bacteria. As alcoholics are known to be deficient in the essential micronutrient zinc, and as zinc is critical for normal immune function, we hypothesized that alcohol-induced zinc deficiency could interfere with the ability of the alveolar macrophage to clear bacteria from the airway. We have shown previously that there is decreased zinc in the alveolar space of alcohol-fed rats compared to control-fed rats. Importantly, zinc supplementation in these alcohol-fed rats restores zinc levels in the alveolar space and normalizes alveolar macrophage phagocytic function in vitro. #### Methods Used In this study we extended these observations to a model of bacterial pneumonia in vivo caused by Klebsiella pneumoniae, a common pathogen in alcoholics. We used a standard isocaloric liquid diet, and adult male Sprague-Dawley rats were divided into four dietary groups: control-fed, alcohol-fed, alcohol-fed supplemented with 100 mg/L of zinc acetate, and alcohol-fed supplemented with 500 mg/L of zinc acetate. After six weeks of this maintained diet, animals were inoculated with 10,000 colony-forming units (CFU) of Klebsiella pneumoniae bacteria intratracheally, and bacterial burden in the lungs was determined 24 hrs later by quantifying the number of colony-forming units per lung. #### Summary of Results Alcohol-fed rats had decreased bacterial clearance (*P* < 0.05) compared to control-fed rats. In contrast, and consistent with our previous findings in vitro, both concentrations of dietary zinc supplementation improved (*P* < 0.05) bacterial clearance in alcohol-fed rats in vivo. #### Conclusions We conclude that dietary zinc supplementation improves lung bacterial clearance in a relevant experimental model of chronic alcohol abuse, and we speculate that zinc could be a simple and effective therapeutic supplement that could decrease the risk of pneumonia and perhaps other infections in alcoholics undergoing treatment for their addiction. ### 312 CHRONIC ALCOHOL EXPOSURE MODULATES EXPRESSION OF RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS IN THE RAT LUNG D. Quintero1, A. Pelaez2, P.O. Mitchell1, D.M. Guidot1 * 1Atlanta VA and Emory University, Atlanta, GA and 2Emory University School of Medicine, Atlanta, GA* #### Purpose of Study Chronic alcohol abuse significantly increases the risk of developing acute lung injury (ALI) in susceptible patients during acute stresses, and we have shown in experimental models that chronic alcohol ingestion alters alveolar epithelial function and increases sepsis-mediated acute lung injury. However, the mechanisms by which alcohol mediates its deleterious effects have not yet been fully elucidated. Receptor for advanced glycation end products (RAGE) is a protein that exists as membrane or soluble isoforms and binds advanced glycation end products (AGEs). The membrane bound isoform induces the release of pro-fibrotic and pro-inflammatory cytokines when bound to ligand; however, the soluble isoform is thought to be protective by acting as a decoy receptor. Rat and human studies have shown that RAGE is released by injurious and inflammatory stimuli into the alveolar space as a soluble protein where it may serve to modulate the inflammatory response. Under normal physiologic conditions, RAGE mRNA and protein are expressed most prominently in the lung, including the basal membrane of alveolar epithelial cells. We hypothesized that chronic alcohol ingestion could decrease RAGE expression in the lung, which could explain in part how it amplifies sepsis-induced lung injury. #### Methods Used To test our hypothesis, we analyzed RAGE expression in lungs from control and 8-week alcohol-fed rats by western blot analysis (protein expression) and real time PCR (gene expression). #### Summary of Results Chronic alcohol ingestion had no significant effect (*P* < 0.05) on RAGE gene expression. However, RAGE protein expression was significantly decreased (*P* < 0.05) in lungs from alcohol-fed rats when compared to control-fed rats. #### Conclusions We conclude that chronic alcohol exposure modulates expression of RAGE in the lung. Additionally, we speculate that alcohol-mediated decreases in RAGE expression have potentially deleterious effects in the lung by decreasing the protective role of soluble RAGE. These findings add to our understanding of the potential mechanisms by which alcohol abuse renders individuals susceptible to ALI. ### 313 THE EFFECTS OF ALCOHOL ON MESENCHYMAL STEM CELL FUNCTION C. Co, M. Rojas, J. Roman *Emory University, Atlanta, GA* #### Purpose of Study Mesenchymal stem cell (MSC) research has been an intense field of investigation within the last decade. Because of their ability to differentiate into various cell lines, these multipotent cells are being considered for many applications in medicine. An intriguing function of MSC is the immune regulatory property they possess. However, the mechanisms for these effects and the factors influencing MSC function have yet to be fully elucidated. We believe that one factor influencing MSC function is alcohol. This might explain why alcohol abuse results in alteration of the immune response. To date, few studies have reported alcohol's effects on impaired MSC differentiation. However, none have described alcohol's effects on MSC immune regulation. #### Methods Used Commercially-manufactured murine bone marrow MSC were cultured in 3 different settings - control media, media with alcohol x24 hr (acute exposure), and media with alcohol for >7 days (chronic exposure). Concentration of alcohol used was 25 mM, equivalent to moderate alcohol consumption in humans. Morphologic changes and cell counts were recorded. The groups were induced to differentiate into adipogenic, osteogenic, and chondrogenic cell lines using standard protocols for 14-21 days. Differentiation was confirmed using the reagents Oil Red O (Adipogenic), Alizarin Red (Osteogenic), Alcian Blue (Chondrogenic). We also tested MSC expression of TNF-α, IL-1β, IL-1ra, G-CSF, and fibronectin using RT-PCR #### Summary of Results MSC exposed to alcohol for 7 days consistently had 20-25% lower cell counts compared to the control group. All three groups had similar cell morphology and showed evidence for differentiation into adipogenic, osteogenic, and chondrogenic lines; however, the staining techniques could not quantify the degree of differentiation. Gene expression for inflammatory cytokines shows differences between groups #### Conclusions These preliminary data show that MSC exposed to alcohol acutely and chronically have differential expression of cytokines. Results also show that chronic alcohol exposure results in decreased proliferation of MSC. Lastly, more stringent protocols utilizing differentiation markers are necessary to quantify differentiation amongst the groups ### 314 ROLE OF INTERLEUKIN-23 IN HOST DEFENSE AGAINST PNEUMOCYSTIS CARINII INFECTION X. Rudner, S. Ruan, J. Shellito *LSU Health Sciences Center, New Orleans, LA* #### Purpose of Study Host defense mechanisms against P. carinii are poorly understood, but pulmonary recruitment of CD4 + T-cells is critical for successful host defense against infection. CD4 + T-cells can be divided into Th1, Th2 and Th17 subsets. IL-23 (an IL-12 family member) maintains and expands the Th17 T-cell population. Our study tested the hypothesis that local release of IL-23 is critical for effective host defense against P. carinii infection, and local delivery of IL-23 can accelerate clearance of the infection. #### Methods Used Normal BALB/c mice were intratracheally challenged with P. carinii. At serial time intervals, mice were sacrificed and lungs were digested with collagenase and DNase. Lung digested cells were incubated with PE conjugated anti F4/80 antibody followed by incubation with anti-PE microbeads to obtain alveolar macrophages. Remaining cells were incubated with CD11c microbeads to obtain dendritic cells. Total RNA was exacted and subjected to real time RT-PCR for IL-23p19 mRNA. To test whether IL-23 gene transfer can accelerate clearance of P. carinii, mice were intratracheally injected with an adenoviral vector encoding IL-23(AdIL-23) or an empty vector (AdNull) 3d prior to P. carinii infection. At 1 and 2 wk post infection, mice were sacrificed and burdens of P. carinii in the lungs determined by real time RT-PCR for P. carinii rRNA. #### Summary of Results There was significant induction of IL-23p19 mRNA in both alveolar macrophages and dendritic cells during infection with P. carinii. Additionally, AdIL-23-treated mice had significantly less fungal burden than the AdNull-treated mice at 2 wk post infection. #### Conclusions IL-23 is released by both alveolar macrophages and dendritic cells in response to P. carinii and local delivery of IL-23 can accelerate clearance of P. carinii infection. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F16.medium.gif) [Figure.](/content/57/1/301/F16) Figure.   ### 315 ABSENCE OF PRO-APOPTOTIC BIM PROMOTES ACCUMULATION OF PULMONARY T-LYMPHOCYTES AND ENHANCES CLEARANCE OF PNEUMOCYSTIS CARINII IFECTION IN MICE S. Ruan, X. Rudner, J. Shellito *LSU Health Sciences Center, New Orleans, LA* #### Purpose of Study Members of the Bcl-2 protein family are critical regulators of developmental programmed cell death. The BH3-only protein, Bim, is essential for the initiation of apoptosis in lymphocytes. We hypothesized that the absence of Bim in pulmonary lymphocytes would prolong lymphocyte lifespan and enhance clearance of Pneumocystis carinii infection. #### Methods Used We infected Bim-/- and Bim +/+ CB57BL/6J mice with P. carinii by intratracheal inoculation. Two weeks later, splenocytes were recovered from both sets of mice and used to reconstitute immunity in P. carinii-infected C.B 17 scid mice by i.p. injection. (untreated scid mice are susceptible to P. carinii pneumonia.) #### Summary of Results The mice reconstituted with Bim-/- spleen cells had higher numbers of lymphocytes in bronchoalveolar lavage than mice reconstituted with Bim +/+ cells at 4 weeks after infection. When CD4 + and CD8 + T-cells were purified from lavaged cells, we found lower caspase 3 levels by ELISA in cells from Bim-/- reconstituted mice than Bim +/+ reconstituted mice. Severity of infection in both groups of mice was assayed by real-time PCR for P. carinii ribosomal RNA. Both groups of mice were able to clear the infectious challenge, but the organism burden in lung tissue from mice adoptively transferred with Bim-/- spleen cells was significantly decreased at 2 and 4 weeks in comparison to mice receiving adoptive transfer +/+ cells. #### Conclusions These findings support a role for the BH3-only protein, Bim, in lymphocyte apoptosis during murine P. carinii pneumonia and support the idea that the absence or silencing of Bim can down regulate T lymphocyte apoptosis, promote survival of T lymphocytes in lung tissue, and enhance clearance of Pneumocystis carinii infection. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F17.medium.gif) [Figure.](/content/57/1/301/F17) Figure.   ### 316 THE THYMOPOIETIC RESPONSE TO PNEUMOCYSTIS CARINII INFECTION X. Shi, J.S. Soblosky, P. Zhang, J.E. Shellito *LSUHSC, New Orleans, LA* #### Purpose of Study Pneumocystis carinii (PC) causes severe pneumonia in HIV-infected patients. CD4 + T cells are known to play a key role in host defense against PC infection. During HIV infection, activated memory CD4 + cells are major target cells destroyed by HIV. Generation of naïve T cells from thymus then becomes essential for host to sustain enhanced T cell turnover. Knowledge about the significance of thymopoiesis in host defense against PC infection remains unexplored. #### Methods Used Thymectomy was performed in male C57Bl/6 mice (5 weeks old). Controls received a sham operation. Three weeks later, PC infection in the lung was induced by intratracheal injection of PC (2 × 10∧5/mouse). The animals were sacrificed 1, 2, 3, 4, 5 and 6 weeks thereafter. #### Summary of Results In sham-operated mice, the number of bone marrow precursors of the earliest thymic progenitors was significantly increased in the bone marrow (30 ± 3 and 66 ± 14 cell/10∧6 BMCs, respectively at weeks 3 and 4, vs. 3 ± 3 cells/10∧6 BMCs in uninfected controls, *P* < 0.05) and blood (15 ± 5 vs. 1 ± 1 cells/10∧6 WBCs at week 4, *P* < 0.05) following PC infection. Hematopoietic stem cells in the bone marrow also increased significantly following PC infection. The numbers of earliest thymic progenitors, double negative (DN) 1, and DN3 cells in the thymus were increased after PC infection. PC infection caused a moderate reduction in naïve and central memory CD4 T cells in the lung-associated lymph nodes and spleen in sham-operated animals. Numbers of naïve and central memory CD4 T cells were further reduced in mice with thymectomy. Total numbers of CD4 + T cells were also significantly reduced in the blood (70 ± 3 vs. 163 ± 6 cells/10∧3 WBCs, *P* < 0.05), lung-associated lymph nodes (105 ± 2 vs. 192 ± 10 cells/10∧3 lymph node cells, *P* < 0.05), and spleen (73 ± 4 vs. 140 ± 6 cells/10∧3 splenocytes, *P* < 0.05) in mice with thymectomy compared to sham-operated controls at week 5 following PC infection. #### Conclusions Thymopoiesis is activated in response to PC infection, which is supported by release of thymic progenitors from bone marrow. This thymopoietic response contributes to maintaining CD4 T cell levels during PC infection and may be essential to host defense against this infection. ### 317 MMP-2, MMP-9, AND FIBRONECTIN EXPRESSION IN CHRONIC HYPOXIA-INDUCED PULMONARY HYPERTENSION IN THE MOUSE H.M. Ward1,2, J. Ritzenthaler1, S. Roser-Page1, J. Roman1,2, C.M. Hart1,2 * 1Emory University, Atlanta, GA and 2Atlanta VA Medical Center, Atlanta, GA* #### Purpose of Study Pulmonary vascular remodeling is characterized by increased thickness of the vascular wall and decreased luminal diameter. Matrix-degrading enzymes of the Matrix Metalloproteinase (MMP) family and the matrix glycoprotein fibronectin have been implicated in tissue remodeling and are produced by vascular cells. We previously showed that chronic hypoxia (CH)-induced pulmonary vascular remodeling and pulmonary hypertension in mice are attenuated by treatment with the PPARγ ligand, rosiglitazone. Therefore, we hypothesized that rosiglitazone attenuates CH-induced pulmonary hypertension and vascular remodeling by inhibiting the expression of the gelatinases MMP-2 and MMP-9 and fibronectin. #### Methods Used To test this hypothesis, male C57Bl/6 mice were exposed to CH (FiO2 10%) or room air for 3 weeks. During the last 10 days of exposure, mice were treated with either rosiglitazone (10 mg/kg/day) or with an equal volume of vehicle by gavage daily. After sacrifice whole lung tissue homogenates were subjected to zymography, RT-PCR, immunohistochemistry and western blotting for MMP-2, MMP-9, and fibronectin. #### Summary of Results We found that CH-induced pulmonary vascular remodeling was not associated with alterations in the expression or activity of MMP-2 and MMP-9. Although previous studies in the rat have suggested that rosiglitazone alters MMP-2 activity in hypoxia-induced pulmonary hypertension in the rat, our preliminary data suggest that MMP-2, MMP-9 are not significantly altered during hypoxia-induced pulmonary hypertension in mice. On the other hand, CH tended to increase fibronectin mRNA levels in the lung, an effect attenuated by rosiglitazone treatment. #### Conclusions These preliminary data suggest that rosiglitazone may reduce hypoxia-induced pulmonary vascular remodeling by modulating fibronectin but not MMP expression. ### 318 ANTIBODY-MEDIATED DEPLETION OF T-LYMPHOCYTES DOES NOT EXACERBATE HYPOXIA- INDUCED PULMONARY HYPERTENSION IN MICE A. Gluzman1, D. Kleinhenz2, D. Neujahr1, C. Hart1,2 * 1Emory University, Atlanta, GA and 2Atlanta VAMC, Atlanta, GA*. #### Purpose of Study Recent work suggested that an intact immune system was protective in the development of pulmonary hypertension in rats. We hypothesized that neutralizing antibody-mediated depletion of T-lymphocytes would exacerbate hypoxia-induced pulmonary hypertension in mice. #### Methods Used Male C57Bl/6 mice were subjected to chronic hypoxia (10% O2) or to room air (Control) for 3 weeks. Each mouse was also injected with anti-CD4 and anti-CD8 antibodies (100 μg each) in PBS or with PBS alone immediately prior to hypoxia exposure and every 3rd day thereafter until the end of the 3-week exposure. Right ventricular systolic pressures (RVSP) were measured by passing a pressure transducer into the right ventricle. After sacrifice, the hearts were dissected, and right ventricular (RV) to left ventricular plus septal (LV+S) weight ratios (RV:LV+S) were determined as an index of RV hypertrophy. Antibody-mediated T-cell depletion was confirmed by flow-cytometric examination of spleens. #### Summary of Results Flow cytometry confirmed that treatment with anti-CD4 and anti-CD8 antibody produced greater than 93% depletion of CD4+ and CD8+ T-lymphocytes outside the thymus as compared with controls. Compared to Control conditions, exposure to chronic hypoxia increased RVSP (from 25.4 ± 2.3 to 34.8 ± 2.2 mmHg, n = 4-5) and RV:LV+S (from 0.255 ±.045 to 0.351 ± 0.073, n = 5). Antibody-mediated T-lymphocyte depletion failed to modulate hypoxia-induced changes in RVSP or RV:LV+S. #### Conclusions Antibody-mediated T-lymphocyte depletion did not exacerbate hypoxia-induced pulmonary hypertension in mice. These findings do not exclude the possibility that more complete elimination of thymic T-cells or more selective manipulation of T-cell subsets might significantly modulate hypoxia-induced pulmonary hypertension pathogenesis in the mouse. ### 319 PEPSIN IN GASTRIC FLUID PROMOTES EPITHELIAL MESENCHYMAL TRANSFORMATION: IMPLICATIONS FOR UNDERSTANDING THE ROLE OF REFLUX IN PULMONARY FIBROSIS F. Ahmad1, J. Ritzenthaler1, J. Roman1,2 * 1Emory University, Atlanta, GA and 2VA Medical Center, Atlanta, GA* #### Purpose of Study Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease with an unknown cause. Patients with IPF often suffer from some form of gastroesophageal reflux disease (GERD), which can range from esophageal reflux to aspiration into the lung. Although GERD has been implicated in the pathogenesis of IPF, its role is controversial and the mechanisms involved in this association remain largely unexplored. Studies suggest that injury to lung epithelial cells might promote lung fibrosis. This process includes the transformation of epithelial cells into mesenchymal-type smooth muscle-like cells with augmented capacity for matrix remodeling and tissue contraction. Because of the perceived importance of this process, termed epithelial-mesenchymal transformation (EMT), we explored the relationship between GERD and EMT in vitro. #### Methods Used We tested the hypothesis that specific components of gastric fluid could stimulate EMT. Specifically, we explored the effects of gastric fluid (HCl with and without pepsin, pH 2.0) versus pepsin (a protein-degrading enzyme) alone on rat lung epithelial type II cells. We incorporated techniques that involved cell culture, western blot analysis for protein production, RT-PCR for RNA analysis, and zymography for detection of enzyme activity. #### Summary of Results We found that exposure to pepsin stimulated the expression of α-smooth muscle actin (αSMA), a marker of EMT. Interestingly, gastric fluid (pH 2.0) in the absence of pepsin failed to stimulate αSMA expression. Of note, pepsin-induced EMT was also associated with increased expression of fibronectin, an extracellular matrix glycoprotein implicated in injury and repair. Furthermore, we determined that pepsin induced the expression of gelatinolytic activity related to matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-7 (MMP-7). #### Conclusions Together, these in vitro observations suggest that pepsin stimulates lung epithelial cells to undergo EMT characterized by increased expression of αSMA, matrix glycoproteins, and matrix-degrading proteases, thereby providing a cellular mechanism by which chronic GERD can promote the progression of IPF, and unveiling potential targets for therapy. ## **Renal, Electrolyte and Hypertension I: Concurrent Session** 2:00 PM Friday, February 13, 2009 ### 320 MECHANISM OF PROTEASE EFFECTS ON SODIUM TRANSPORT IN CORTICAL COLLECTING DUCT CELLS Z. Feng2, K.S. Hering-Smith1,2,3, L.L. Hamm1,2,3 * 1Tulane University, New Orleans, LA; 2Tulane University, New Orleans, LA and 3SLVHCS, New Orleans, LA* #### Purpose of Study The epithelial sodium channel (ENaC) in collecting duct cells is involved in the regulation of sodium balance and blood pressure. Proteases in the luminal aspect of the distal nephron have been shown to activate sodium channels. These effects can be mimicked by exogenous trypsin and inhibited by aprotinin, a serine protease inhibitor. Recently the actions of proteases have been postulated to be secondary to the release of inhibitory peptides from the alpha and gamma subunits of ENaC. An eight amino acid synthetic peptide (LPHPLQRL) representing the inhibitory domain within the alpha subunit of ENaC has been shown to inhibit sodium current in collecting duct cells. The present studies were designed to determine whether luminal proteases have other actions independent of these inhibitory peptides. #### Methods Used M-1 cells, a mouse cortical collecting duct model, were studied on permeable supports. Electrophysiological measurements were performed with Epithelial Voltohmmeter (EVOM, WPI). Peptide LPHPLQRL was synthesized and HPLC purified by GenScript (Piscataway, NJ). #### Summary of Results Apical LPHPLQRL inhibited sodium current, as previously shown, by 36% (compared to control) after 30 minutes of application. However in contrast to the effects of trypsin and aprotinin, there was no effect on transepithelial resistance. Apical addition of trypsin after application of LPHPLQRL stimulated sodium current by 36% and transepithelial resistance by 8% despite the continued presence of the inhibitory peptide. However, trypsin degradation of LPHPLQRL could not be excluded. In other experiments, apical addition of aprotinin after application of LPHPLQRL decreased transepithelial resistance by 62% and to a lesser extent sodium current even in the continued presence of the inhibitory peptide. #### Conclusions These results indicate that luminal proteases alter sodium transport in collecting duct cells both via the release of ENaC inhibitory peptides and in addition via other mechanisms including effects on paracellular permeability and resistance. ### 321 ATRIAL NATRIURETIC PEPTIDE INDUCED NATRIURESIS INVOLVES INHIBITION OF DISTAL NEPHRON FRACTIONAL SODIUM REABSORPTION D. Zhao, L. Navar *Tulane University School of Medicine, New Orleans, LA* #### Purpose of Study Atrial natriuretic peptide (ANP) has been reported to inhibit sodium reabsorption in the proximal nephron and the collecting duct segments, however, their contribution to the overall ANP induced natriuresis has remained unclear. #### Methods Used This study was performed to determine the effects of acute infusions of ANP at low (0.1 ng/g body weight (BW)/min, n = 6) and high doses (0.2 ng/g BW/min, n = 6) on renal hemodynamics and distal nephron sodium reabsorption determined after blockade of the two major distal nephron sodium transporters with amiloride (5 mg/kg BW) plus bendroflumethiazide (12 mg/kg BW) in male anesthetized C57/BL6 mice. #### Summary of Results The lower dose of ANP increased distal sodium delivery (DSD, 2.2 ± 0.2 μEq/min versus 1.5 ± 0.2 μEq/min, *P* < 0.05), but did not change fractional reabsorption of DSD as compared with control (85.3 ± 1.7% versus 81.0 ± 4.0%, *P* > 0.05) limiting the magnitude of the natriuresis. In contrast, the higher dose increased DSD (2.8 ± 0.3 μEq/min, *P* < 0.01) and also decreased fractional reabsorption of DSD (67.4 ± 4.5%, *P* < 0.05), thus markedly augmenting the natriuresis. The relationships between DSD and distal sodium reabsorption were similar in control (y = 0.884 × - 0.100, *P* < 0.001) and low dose group (y = 0.859x - 0.009, *P* < 0.001) demonstrating load dependence of distal nephron sodium reabsorption; however, the relationship was suppressed in the high dose group (y = 0.956 × - 0.752, *P* < 0.05). #### Conclusions In conclusion, ANP mediated increases in DSD alone exert modest effects on the sodium excretion, the augmented natriuresis response to the higher dose of ANP occurs primarily as a consequence of inhibition of fractional reabsorption of distal sodium delivery. ### 322 PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP-38) REDUCES APOPTOSIS AND RENAL TUBULAR DAMAGE IN CISPLATIN INDUCED AKI S. Balamuthusamy, M. Li, E.E. Simon, V. Batuman *Tulane University Medical School, New Orleans, LA* #### Purpose of Study Cisplatin (cis-diamminedichloro-platinum II, CDDP) can cause acute kidney injury (AKI) in humans and mice by several mechanisms. PACAP-38 was shown to have protective effects in myeloma kidney and ischemic renal injury. We evaluated the potential renoprotective effects of PACAP-38 on CDDP induced kidney injury in mice. #### Methods Used Male C57BL/6 mice were treated with 20 mg/kg cisplatin intraperitoneally. Twenty nanomoles of PACAP38 was given intraperitoneally 1 hr before cisplatin and additional doses were given at 24 and 48 hr after the initial dose. Control group of mice was injected intraperitoneally with saline at same frequency and volume as the experimental mice. Mice were euthanized 24 hr after the final injection of PACAP38. Kidneys were harvested and fixed with 10% formalin for histopathological evaluation. Tail vein blood was collected for BUN and creatinine measurement. Effects of PACAP and cisplatin were also analyzed in vitro with human PTEC in cell culture. Flow cytometry and immunoblots were used to measure p53, integrins, fibronectin and laminin. #### Summary of Results PACAP treatment significantly decreased serum creatinine (1 mg/dl in cisplatin+PACAP group vs 2.5 mg/dl in cisplatin only group) and BUN (100 mg /dl in cisplatin+PACAP mice vs 200 mg mg/dl in cisplatin alone mice; *P* < 0.01) in cisplatin treated C57BL/6 mice when compared to mice that were given cisplatin alone. There was marked decrease in the severity and extent of tubular necrosis in cisplatin mice co-treated with PACAP on histopathological evaluation. PACAP38 treatment or p53 siRNA transfection partially reversed the decrease in fibronectin (cisplatin-25 dRn vs PACAP+cisplatin -40 dRn: *P* < 0.01) and collagen IV (cisplatin-3 dRn vs cisplatin+PACAP-32 dRn; *P* < 0.01) in HK-2 cells. PACAP also reversed cisplatin induced changes in the expression of the αVβ3 integrin on the surface of HK-2 cells in flow cytometry analysis. #### Conclusions PACAP significantly reduces acute kidney injury, downregulates apoptotic pathways and prevents suppression of collagen IV, fibronectin and integrins in cisplatin treated mice and human PTEC. Reduction in apoptosis and decreased suppression of fibronectin, collagen IV and αVβ3 with PACAP treatment in PTEC could explain the reduced ATN in cisplatin AKI-models. ### 323 ANGIOTENSIN (ANG) II-INDUCED URETERIC BUD (UB) BRANCHING MORPHOGENESIS IS MEDIATED VIA EPIGENETIC MODIFICATION OF THE GENOME T. VanBuren, R. Song, I.V. Yosypiv *Tulane University School of Medicine, New Orleans, LA* #### Purpose of Study We recently reported that Ang II, acting via the AT1 receptor, stimulates UB branching morphogenesis by induction of the UB morphogenetic program gene expression (Yosypiv et al. Kidney International, 2008). In the present study, we tested the hypothesis that these effects of Ang II are mediated by changes in UB morphogenetic program gene acetylation and methylation status. To begin explore this hypothesis, we examined the effect of Ang II on global histone 3 (H3) acetylation, trimethylation of lysine (K) on H3K4 and H3K9. Since deacetylation of histone proteins, catalyzed by histone deacetylases (HDACs), is a common epigenetic modification of chromatin typically associated with gene silencing, we also investigated the effect of Ang II on HDAC-1 expression. #### Methods Used Paired CD1 mice embryonic (E) day E12.5 metanephroi were grown on polycarbonate transwell filters located on top of DMEM/F12 medium alone (control, n = 4) or in the presence of Ang II (10-5 M, n = 4). After 24 hours in culture, extracted proteins were analyzed by Western blotting. #### Summary of Results Ang II decreased acetylation of H3 in whole metanephroi. This was accompanied by an increase in HDAC-1 protein expression in whole metanephroi and ureteric bud-derived cells (UB cells). Treatment with Ang II did not affect H3K4 or H3K9 trimethylation in whole embryonic kidneys. #### Conclusions We conclude that Ang II-induced upregulation of HDAC-1 expression leads to decreased global H3 acetylation. These changes may alter acetylation status of core histones and Ang II-dependent transcription factors to promote UB cell proliferation and branching morphogenesis during early kidney development. ### 324 IMMUNOLOCALIZATION AND EXPRESSION OF BRADYKININ B1 RECEPTORS DURING NEPHROGENESIS P. Bulut, S. Dipp, S. El-Dahr *Tulane University School of Medicine, New Orleans, LA* #### Purpose of Study The kallikrein-kinin system regulates renal function and blood pressure by acting on two G protein coupled bradykinin (BK) receptors, B1R and B2R. The B2R gene is developmentally regulated and is highly expressed during terminal nephron differentiation. Previous studies have shown that B2R-deficient mice are prone to salt-sensitive hypertension. There is currently no data regarding the role of B1R in renal development. The B1R is known to be a G protein-coupled receptor that is induced by cell injury and is resistant to desensitization. As an initial step in elucidating the developmental role of the B1R, we investigated the spatiotemporal expression of B1R during renal organogenesis. #### Methods Used B1R cellular localization was performed on kidney tissue sections from embryonic day E14.5 and E17.5 and postnatal day 1 by immunohistochemistry and immunoflourescence utilizing a polyclonal anti-B1R peptide antibody. The segmental nephron identity of B1R immunoreactivity was determined by co-staining with markers of the collecting duct (Dolichos biflorus), proximal tubule (Dolichos tetraglonus), and nephron progenitors (Pax2). #### Summary of Results The results showed that B1R is primarily expressed in the proximal tubule in all age groups. At E14.5, the abundance of immunoreactive B1R was relatively low and was confined to few cells in the metanephric mesenchyme and developing proximal tubules. The ureteric bud and its derivatives did not express B1R. Abundance of B1R increased progressively during development. On E17.5, B1R was enriched in the proximal tubular cells and its precursors. On postnatal day 1, B1R was clearly expressed on the luminal aspect of the proximal tubule but not in the nephrogenic zone, collecting duct or glomeruli. There was no significant up-regulation of B1R detectable with immunhistochemistry in B2R-/-. #### Conclusions 1) B1R expression in the developing kidney correlates closely with nephron maturation; 2) low expression of B1R in ureteric bud branches and in early nephron precursors suggests that B1R is unlikely to play a role in early events of kidney development; and 3) enrichment of B1R in maturing proximal nephron suggests a role for this receptor in terminal differentiation and/or functional maturation of the proximal tubule. ### 325 IMBALANCE OF ANGIOGENIC FACTORS IN A RAT MODEL OF PREECLAMPSIA E. Agunanne, M. Uddin, D. Horvat, J. Puschett *Texas A & M Health Science Center /Scott & White, Temple, TX* #### Purpose of Study Preeclampsia may result from an imbalance between circulating pro-angiogenic factors such as vascular endothelial growth factor (VEGF), placental growth factor (PlGF), transforming growth factor B1 (TGF-B1), and anti-angiogenic factors: soluble fms-like tyrosine kinase (sFlt1) and soluble endoglin (sEng). We investigated these factors in our rat model of preeclampsia (PE) in which marinobufagenin (MBG) plays an important role. #### Methods Used Rats were divided into 4 groups: control, non pregnant (C, n = 5), normal pregnant (NP, n = 5), pregnant animals which received DOCA and whose drinking water had been replaced with 0.9% saline (PDS, n = 5) and normal pregnant animals infused with MBG (NPM, n = 5). These factors were measured in plasma and placental homogenates of NP, PDS and NPM were measured with commercially available kits. #### Summary of Results Plasma level of sFlt1 was significantly higher in NP, PDS and NPM compared to C (C: 379.6 ± 21.8, NP: 2778.8 ± 51.4, PDS: 2815.6 ± 46.5, NPM 2483.2 ± 59.06 pg/ml, *P* < 0.001 for C vs. NP, C vs. PDS and C vs. NPM). Plasma VEGF (C: 20.4 ± 1.2, NP: 29.2 ± 1.8, PDS: 20.6 ± 1.1, NPM: 19.2 ± 1.69 pg/ml) and PlGF (C: 16.1 ± 1.2, NP: 26.5 ± 1.9, PDS: 18.2 ± 1.6, NPM 16.4 ± 2.3 pg/ml) levels were significantly lower in our rat model of PE compared to NP (*P* < 0.05 for PDS vs. NP). The plasma ratio of sFlt1: PlGF of NP was higher than C, and a further significant increase was observed in both PDS and NPM compared to NP (C: 28 ± 2, NP: 126 ± 3, PDS: 168 ± 3; NPM: 151 ± 5pg/ml, *P* < 0.001 for C vs. NP; *P* < 0.05 for NP vs. PDS and NP vs. NPM). The placental concentration of sFlt1 was significantly increased in PDS and NPM, compared to NP (NP: 55.1 ± 4.5, PDS: 73.2 ± 6.1, NPM: 140.4 ± 20.4 ng/g tissue, *P* < 0.05 for NP vs. PDS and NP vs. NPM). Plasma levels of sEng were higher in the PDS, NPM, and NP compared to C (C: 232.3 ± 15.7, NP: 821.5 ± 22.36, PDS: 830.7 ± 25.3, NPM: 822 ± 13.09 pg/ml, *P* < 0.05 in each comparison). Plasma TGF-B1 levels were significantly reduced in the NP, PDS and NPM compared to the C (C: 6.22 ± 0.63, NP: 4.34 ± 0.69, PDS: 4.1 ± 0.35 and NPM: 4.06 ± 0.289 ng/ml, *P* < 0.05 in each case). #### Conclusions We conclude that angiogenic imbalance contributes in part to PE-like features in our rat model of PE and that MBG may play a role in this imbalance. ### 326 CLONE 1135 - RELATED PROTEIN IS A KEY SOLUBLE MEDIATOR OF PROTEINURIA IN MINIMAL CHANGE DISEASE L. Clement, S. Chugh *University of Alabama at Birmingham, Birmingham, AL* #### Purpose of Study Clone 1135 related protein circulates in normal plasma as a cleaved protein, and its full length form is also secreted by podocytes in experimental and human minimal change disease. The biological properties of this gene and its protein were assessed to determine its role in primary glomerular disease. #### Methods Used Transgenic rats that express this gene specifically in podocytes (for podocyte secreted protein) and adipose tissue (for increased circulating levels of this protein) were generated. In vivo studies were conducted to assess the role of this protein in minimal change disease. Regulation of the 1135 gene by the ZHX family of transcriptional factors was also studied. #### Summary of Results Podocyte specific transgenic rats develop diffuse widening of foot processes and albuminuria, whereas adipose tissue specific expression does not cause albuminuria or podocyte morphological changes. Induction of mild puromycin nephrosis substantially exacerbates proteinuria in both transgenic strains compared to wild type controls. Following induction of puromycin nephrosis, increased circulating levels of intact oligomeric 1135 protein were higher in podocyte specific transgenic rats than their wild type counterparts. ZHX over expression in cultured GECs and promoter - reporter studies reveal that the 1135 gene is upregulated by ZHX1 and ZHX2, and downregulated by ZHX3. Mutagenesis of the first interspecies consensus CdxA binding site (closest to ATG) results in precipitous decline in promoter activity and loss of ZHX regulation of the 1135 promoter. #### Conclusions Elevated levels of podocyte secreted and circulating clone 1135 related protein are pathogenic in primary glomerular disease and are key mediators of proteinuria. ZHX proteins mediate changes in the expression of this gene during the development of podocyte disease. ### 327 HIGH SALT EXACERBATES PROTEINURIA IN CHRONIC ANGIOTENSIN-II INFUSED RATS B.M. Lowenburg1, J.A. Planchard1, V.L. Martin1, P.D. Davis1, F.T. Botros1,2, L. Navar1,2, K.D. Mitchell1, M.C. Prieto-Carrasquero1 * 1(Tulane University, School of Medicine, New Orleans, LA and 2Tulane University, New Orleans, LA* #### Purpose of Study Under normal conditions, increased salt intake inhibits both systemic and intrarenal renin angiotensin system (RAS). However, there is evidence that when angiotensin II (Ang II) levels are not suppressed increased dietary salt intake exacerbates hypertension and cardiovascular and renal injury. In the present study we examined the effect of a high salt (HS) diet on systolic blood pressure (SBP) and proteinuria in chronic Ang II-infused hypertensive rats with and without RAS blockade with an Ang II type I receptor blocker, losartan (Los). #### Methods Used Male Sprague-Dawley rats were divided into four groups as follows: 1) sham + HS [n = 5]; 2) Ang II [n = 3]; 3) Ang I + HS [n = 5]; 4) Ang II + HS + Los [n = 5]. Ang II was infused via SC mini-pump (80 ng/min) for 14 days and HS (8% NaCl) was administered in the diet while Los in drinking water (30 mg/L). #### Summary of Results SBP, measured by tail cuff-method, progressively increased in Ang II and Ang II + HS rats (3-days: 171 ± 11 mmHg; 181 ± 11 mmHg; 7-days: 195 ± 12 mmHg; 191 ± 10 mmHg; 14-days: 228 ± 9 mmHg; 228 ± 10 mmHg) compared to sham + HS (128 ± 7 mmHg; *P* < 0.05). Losartan attenuated the increases in SBP during the two-weeks of treatment (14-days: 144 ± 9 mmHg; *P* < 0.05). Rats receiving Ang II + HS showed marked proteinuria measured in 24h-urine collections (79 ± 26 mg/day) which was greater than in Ang II group. The protein excretion in the Ang II + HS + Los was not different than in controls (18 ± 1 mg/day vs. 29 ± 2 mg/day. *P* < 0.05). #### Conclusions These findings demonstrate that there was no difference between SBP in rats with Ang II-induced hypertension and those who also received HS, suggesting that HS does not exert an additive effect on SBP. However, rats fed with HS in addition to Ang II infusion exhibited substantially more proteinuria, indicating that HS might contribute to glomerular kidney damage. Losartan treatment reduced SBP and proteinuria in HS + Ang II rats. The results support the hypothesis that high salt affects proteinuria independently of SBP and Ang II effects during Ang II-dependent hypertension suggesting a direct action on glomerular protein barrier. Grant support from NIH and Merck & Co., Inc. ### 328 INFLAMMATORY CASPASES ARE UPREGULATED IN RENAL FIBROSIS OF OBSTRUCTIVE KIDNEY DISEASE N. Swavely1, P. Gooz1,2, R. Visconti2, S. Sivritas1, W. Fitzgibbon1, M. Gooz1 * 1Medical University of South Carolina, Charleston, SC and 2Medical University of South Carolina, Charleston, SC* #### Purpose of Study Renal fibrosis is a prevalent complication of many conditions including diabetes, hypertension, and obstructive renal disease. This fibrotic pathology can be mirrored using the chronic unilateral ureteral obstruction (UUO) model, which is characterized by inflammatory response, progressive accumulation of extracellular matrix molecules in the interstitial space of the kidney and apoptosis of tubular epithelial cells. Some specific proteins, such as tumor necrosis factor α (TNF-α) and caspases 3 and 8, have been implicated in UUO induced apoptosis previously, but no detailed analysis has yet been done on the apoptotic pathways in interstitial fibrosis. The aim of our study was to dissect apoptotic signal transduction mechanisms in tubulointerstitial fibrosis by characterizing the mRNA transcripts related to these signaling pathways. #### Methods Used We used mouse kidneys harvested 10 days after UUO surgery. To demonstrate and quantify the level of fibrosis in the interstitium, we employed picrosirious red staining on paraffin embedded tissue sections. To identify genes of apoptotic molecules we used the "Mouse apoptosis PCR array" from SuperArray which includes primers for 84 pro- and anti-apoptotic molecules. #### Summary of Results We found a significant, 22-fold increase in collagen expression in the interstitium of UUO kidneys over the sham. Using PCR array we have identified 12 highly (5-17 fold) upregulated genes in the UUO kidney. Interestingly most of these genes were related to inflammation rather than apoptosis. These genes included caspases 1, 4, and 12, which are inflammatory caspases and 4 TNF-α associated genes including both pro-apoptotic (TNF receptor soluble factor 10, Fas ligand, Cd40) and anti-apoptotic molecules (Traf1). Further, the anti-apoptotic monocyte cytokine IL-10 was also significantly increased. #### Conclusions Inflammation has an important role in the development of renal damage during fibrotic processes following UUO, evident from both the upregulation of inflammatory caspases and also the TNF associated genes. This work was supported by NIH DK070054, the DCI and REAP from the VA to MG, P20-RR1-16434 and CO6-RR018823 from the NCRR to RV, and by P20 RR016434 from the SC COBRE of the NCCR to PG. ## **Southern Society for Clinical Investigation and International Academy of Cardiovascular Sciences - NA Chapter Joint Session II: Young Basic Scientist Award** 9:30 AM Saturday, February 14, 2009 ### 329 UPREGULATION OF GALECTIN-1 BY HOMOCYSTEINE IN VASCULAR SMOOTH MUSCLE CELLS: A POTENTIAL NEW THERAPEUTIC TARGET FOR ATHEROSCLEROSIS B.M. Atteia1, P. Delafontane1, P. Lucchesi2 * 1Tulane University, New Orleans, LA and 2Nationwide Children's Hospital, Columbus, OH* #### Purpose of Study The relevance of hyperhomocysteinemia (HHCY) as a risk factor for atherosclerosis is still unkown. In order to clarify the role of HHCY in the pathogenesis of atherosclerosis, the present study therefore investigated the effects of a pathophysiological concentration of homocysteine (HCY) (150 μM) on VSMC function in vitro. #### Methods Used Primary vascular smooth muscle cell (VSMC) were isolated from rat thoracic aortas and were grown in cultured medium-199. VSMC were treated for 24 h with pathophysiological levels of HCY (150 μM). #### Summary of Results Paradoxically, HCY increased both proliferation and apoptosis of VSMC and superoxide anions. Proteomic analysis showed that HCY upregulated several proteins including the beta-galactoside binding lectin, galectin-1. Strikingly, HCY increased the motility and migration of VSMC. Immunocytochemistry results indicted that galectin-1 expression is co-localized with apoptotic cells. Furthermore, upregulation of galectin-1 was associated with increased expression of nitrotyrosine and active caspase-3. Downregulation of galectin-1 by transfection of VSMC with galectin-1 specific small interfering RNA (siRNA) reduced HCY-induced VSMC apoptosis, superoxide anions production, VSMC proliferation and migration. #### Conclusions Our findings suggest that galectin-1 has pleotropic effects on VSMC and that it is an important mediator of many of the effects of HCY on VSMC. These findings provide insights into mechanisms whereby HCY promotes atherogenesis and provide a potential new therapeutic target for atherosclerotic vascular disease. ### 330 DIRECT PHARMACOLOGIC INHIBITION OF MYELOID DIFFERENTIATION FACTOR-88 AS A NOVEL THERAPEUTIC TARGET AFTER ACUTE MYOCARDIAL INFARCTION B.M. Van Tassell1, F.N. Salloum2, A. Varma2, N.N. Hoke2, A. Abbate2 * 1Virginia Commonwealth University, Richmond, VA and 2Virginia Commonwealth University, Richmond, VA*. #### Purpose of Study Experimental and clinical evidence confirm the role of inflammatory signalling in pathologic cardiac remodeling after acute myocardial infarction (AMI). Myeloid differentiation factor 88 (MyD88) is a naturally occurring protein that mediates the effects of multiple pro-inflammatory pathways, including interleukin-(IL)-1, IL-18, and the toll-like receptor family. IMG2005 is a novel oligopeptide that directly inhibits MyD88 homodimerization. We hypothesized that IMG2005 would prevent cardiac remodeling in a mouse model of AMI. #### Methods Used Fourteen ICR mice underwent permanent surgical coronary artery ligation. Mice received daily intraperitoneal injections of IMG2005 1 mg/kg (n = 7) or NaCl 0.9% (n = 7) for 14 days. Animals underwent transthoracic echocardiography at baseline, 7 days, and 14 days after surgery. #### Summary of Results IMG2005 attenuated left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) versus saline at 14 days (see figure). IMG2005 mice also exhibited partial inhibition of aneurysm score (3 vs 4, *P* < 0.05) and a trend towards improved survival (*P* = 0.06), but no observable changes in fractional shortening or ejection fraction at 14 days. #### Conclusions MyD88 inhibition with IMG2005 prevents unfavorable cardiac remodeling after experimental AMI in mice. To our knowledge, ours is the first model to investigate the effects of direct MyD88 inhibition in vivo. Pharmacologic inhibition of MyD88 may be a valuable therapeutic strategy in post-infarction remodeling and heart failure. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F18.medium.gif) [Figure.](/content/57/1/301/F18) Figure.   ### 331 OXIDATIVE STRESS IN CARDIAC MITOCHONDRIA HARVESTED FROM RATS WITH ALDOSTERONISM. RESPONSE TO SPIRONOLACTONE OR AMLODIPINE COTREATMENT G. Kamalov, P.A. Deshmukh, R.A. Ahokas, Y. Sun, S.K. Bhattacharya, I.C. Gerling, K.T. Weber *University of Tennessee Health Science Center, Memphis, TN* #### Purpose of Study In rats receiving chronic aldosterone/salt treatment (ALDOST), to raise plasma ALDO levels to those found in human CHF, marked excretory Ca2+ losses lead to ionized hypocalcemia and secondary hyperparathyroidism with parathyroid hormone-mediated intracellular [Ca2+] overloading of cardiomyocytes and mitochondria to account for an induction of oxidative stress. Cotreatment with either spironolactone (S), an aldosterone receptor antagonist, or amlodipine, an L-type Ca2+ channel blocker (CCB), attenuates [Ca2+] overloading and are cardioprotective. Herein, we hypothesized cotreatment of rats receiving ALDOST with either S or CCB would attenuate mitochondrial oxidative stress. #### Methods Used Four groups of 8-wk-old Sprague-Dawley rats: untreated, age-/gender-matched controls (C); rats receiving ALDOST (A) for 4 wks (0.75 μg/h by osmotic minipump, together with 1% NaCl/0.4% KCl in drinking water); 4 wks A + S (150 mg/kg/day by gavage); and 4 wks A + amlodipine (CCB, 5 mg/kg/day by gavage). We monitored oxidative stress in isolated cardiac mitochondria with succinate-induced production of hydrogen peroxide (H2O2) by Amplex Red/horseradish peroxidase assay, malondialdehyde (MDA) concentration, a marker of lipid peroxidation, by N-methyl-2-phenylindole, a chromogenic reagent. Glutathione peroxidase activity (GPx) and the ratio of reduced to oxidized glutathione were determined using commercial kits. Results were expressed as mean ± SEM and analyzed using ANOVA with Scheffé's post-hoc analysis. #### Summary of Results * *P* < 0.05 ALDOST vs. C; †*P* < 0.05 A + S vs. ALDOST and ‡ *P* < 0.05 A + CCB vs. ALDOST: #### Conclusions Various biomarkers of oxidative stress are increased in mitochondria harvested from hearts at 4 wks ALDOST. Cotreatment with either S or CCB markedly attenuated the appearance of oxidative stress in these organelles and this may contribute to the cardioprotective properties of these agents in rats with aldosteronism. View this table: [Table34](/content/57/1/301/T34) ### 332 ESTROGEN INHIBITS NF-KB P65 BINDING TO THE PROMOTERS OF INFLAMMATORY GENES IN VASCULAR SMOOTH MUSCLE CELLS D. Xing1, S. Nozell2, Y. Chen1, S. Oparil1 * 1University of Alabama at Birmingham, Birmingham, AL and 2University of Alabama at Birmingham, Birmingham, AL* #### Purpose of Study The NFkB signaling pathway is critical for the expression of a variety of genes involved in vascular inflammation. We demonstrated that estrogen (17β -estradiol, E2) inhibits expression of these genes in an estrogen receptor dependent manner in balloon injured rat carotid arteries and in rat aortic smooth muscle cells (RASMCs). This study tested the hypothesis that E2 inhibits the ability of NF-kB to bind to the promoters of these genes. #### Methods Used Quiescent RASMCs were pretreated with E2 or vehicle for 24 hrs, then treated with tumor necrosis factor (TNF)- α for 6 hrs. Cells were fixed, and nuclei were collected and sonicated. Samples were immunoprecipitated (IP) with antibodies specific for NF-kB p65 and analyzed by PCR using primers specific for each promoter. #### Summary of Results Basal levels of p65 were high at the monocyte chemotactic protein (MCP)-1 and cytokine-induced neutrophil chemoattractant (CINC)-2β promoters, moderate at the intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 promoters, and low at the vascular endothelial growth factor (VEGF) promoter in RASMCs (lane 1). TNF-α increased levels of p65 significantly at all promoters analyzed (lane 3), and these effects were reduced by E2 (lane 4). #### Conclusions E2-inhibited expression of inflammatory mediators in the setting of acute vascular injury may be mediated, in part, by inhibit binding of NF-kB p65 to promoters of these genes. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F19.medium.gif) [Figure.](/content/57/1/301/F19) Figure.   ## **Clinical Epidemiology and Preventive Medicine Concurrent Session** 1:00 PM Saturday, February 14, 2009 ### 333 BIRTH INJURIES IN POSTTERM INFANTS BORN TO OBESE WOMEN D.R. Halloran1, Y. Cheng2, A.B. Caughey2 * 1Saint Louis University, St Louis, MO and 2University of California San Francisco, San Francisco, CA*. #### Purpose of Study Maternal obesity and postterm gestation are independently associated with increased perinatal complications including birth injuries. The purpose of the study was to determine the risk of birth injury in postterm versus term infants across maternal weight categories. #### Methods Used This is a population-based cohort study utilizing information from birth certificates linked to hospital discharge data for all live, singleton infants born to Missouri residents between 1993 and 1999, excluding infants born by cesarean section or born to underweight or diabetic mothers (N = 302,933). We performed logistic regression analysis using birth injury (from birth certificates or hospital records) as the dichotomized outcome and the gestational age as the primary exposure (from birth certificates). The primary effect modifier was maternal prepregnancy BMI: normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (≥30 kg/m2). #### Summary of Results 24% of infants were born at 39 weeks (referent), 42% at 40 weeks, 12% at 41 weeks, 2% at 42 weeks. 64% of mothers were normal weight, 22% were overweight, and 15% were obese. The overall rate of birth injury was 36.5 per 1000 births. Adjusted odds ratios (aOR) are reported for birth injury by maternal weight adjusting for maternal age, race, education, parity, tobacco history, and presence of hypertension. #### Conclusions Obesity does not appear to be an independent risk factor for birth injuries after adjusting for confounders. There does not appear to be an interaction between postterm delivery and increasing maternal BMI in birth injury rates. View this table: [Table35](/content/57/1/301/T35) ### 334 THE PREVALENCE AND PREDICTORS OF EARLY CHILDHOOD CARIES IN YOUNG CHILDREN. A STUDY FROM THE SOUTH CAROLINA PEDIATRIC PRACTICE RESEARCH NETWORK (SCPPRN) C.L. Hipp2, E.J. McGee2, L.M. Johnson4, P.J. Hletko3,5, P.M. Darden1,3 * 1Med Univ of SC, Charleston, SC; 2Med Univ of SC, Charleston, SC; 3Med Univ of SC, Charleston, SC; 4Med Univ of SC, Charleston, SC and 5Georgetown Pediatrics, Georgetown, SC* #### Purpose of Study The prevalence of caries in children under 5 years is poorly described. We measured the prevalence of and risk factors for Early Childhood Caries (ECC) in young children. #### Methods Used Parents of patients 3 to 5 years of age being seen for well care in two practices in SCPPRN completed a survey regarding dental caries. A pediatric trained dentist performed a dental exam on the child. The outcome was dental caries. Predictors included type of feeding, fluoridated water, and fruit juice. Control variables were insurance (Medicaid/Private), race (white/black) and clinic. #### Summary of Results 52 children in each clinic (total of 104) were surveyed. Most children were covered by Medicaid (86%), were black (79%), and 3 years old (66%). Few had been exclusively breast fed (5%). In these children 54% had caries. Most children (72%) reported having received preventive dental care. The prevalence of ECC did not vary by practice, age, fluoridated water, preventive dental care or juice consumption. ECC did vary by insurance with Medicaid higher than private (60% v. 21%, *P* < 0.01) and race, with black higher than white (60% v. 30%, *P* = 0.01). In a multivariable logistic model predicting caries and including practice, insurance, age, fluoridated water, preventive dental care only Medicaid insurance v. private was significant (OR 5.2, 95% CI 1.2-23.0). Race could not be included because of collinearity with insurance. #### Conclusions Our results indicate that early childhood caries is a common condition that occurs prior to 3 years of age. In our high risk population efforts to prevent ECC have to start early, new and innovative strategies must be explored. Most strategies usually recommended did not seem effective in this population. Other interventions such as dental varnish might be more effective. ### 335 RURAL PATIENTS' KNOWLEDGE, ATTITUDE AND BEHAVIOR ABOUT INITIAL AND REPEAT MAMMOGRAPHY C.L. Arnold1, A. Rademaker2, M.V. Bocchini1, P.F. Bass1, C. Reynolds1, T.C. Davis1 * 1LSU Health Sciences Center, Shreveport, LA and 2Northwestern University, Chicago, IL* #### Purpose of Study Regular breast cancer screening rates are low in Federally Qualified Health Centers (FQHCs). To determine more effective strategies to increase initial and repeat breast cancer screening, we are conducting a randomized control trial in 6 FQHCs in North Louisiana. This report presents baseline data on the knowledge, attitudes and behavior (KAB) of women 40 and over in 4 rural FQHCs. #### Methods Used Eligible patients (women >39 who had not received a mammogram in the last 2 years and/or who had not had breast cancer) were given a structured interview that assessed literacy and breast cancer screening KAB. #### Summary of Results Of the 203 patients interviewed to date: 52% are AA, 48% white; 33% have not completed high school and 35% are reading <9th grade level. 85% reported they had received a recommendation for mammography from a doctor. 77% had previously had a mammogram, yet 53% of these had not been rescreened in 4 or more years. The most common reasons women reported not getting a mammogram was because they put it off (63%) or they had not had any problems (13%); only 9% said it was because they were afraid they would find out they had cancer. Attitudes about mammograms were positive: 95% believed if breast cancer is detected early their chances of survival are good to very good. 92% reported if they would want to know if they had breast cancer. The most common misconception about mammograms was the age of initial screening - 78% believed it was < age 40. Among commonly perceived barriers, 71% reported mammograms were uncomfortable; however, only 20% believed they were embarrassing or thought they were a lot of trouble (15%). In these rural areas, 87% reported it would be easy to get transportation to get a mammogram. #### Conclusions This data indicates that among women cared for in rural FQHCs, lack of knowledge about breast cancer screening does not appear to be the issue. The majority of women had had an initial mammogram and most had received a recommendation from their doctor. However, these women were not up to date with their screening. Commonly cited barriers in the literature, such as transportation, embarrassment and fear, were not reported to be an issue with these women. ### 336 WHAT DO RURAL PATIENTS KNOW ABOUT COLORECTAL CANCER SCREENING? M.V. Bocchini1, C.L. Arnold1, A. Rademaker2, P.F. Bass1, K. Davis1, T. Davis1 * 1LSU Health Sciences Center - Shreveport, Shreveport, LA and 2Northwestern University, Chicago, IL* #### Purpose of Study To assess rural Federally Qualified Health Center (FQHC) patients' knowledge, attitudes and behavior (KAB) about colorectal cancer (CRC) screening. #### Methods Used Structured interviews assessing literacy and CRC screening KAB were given to eligible patients in 4 rural FQHCs. Patients were eligible if they were ≥age 50, had not had CRC or were not up to date with CRC screening. #### Summary of Results Of 186 patients enrolled to date, 80% were female, 50% AA and 50% white. 36% had not completed high school and 31% were reading ≤8th grade level. CRC screening rates were low, 11% of patients reported they had completed a FOBT; two thirds of these (66%) said they had not been screened in >3 years. Only 26% reported their doctor had recommended CRC screening. Of these 82% had received recommendation for colonoscopy and 22% for FOBT. Only 9% of patients reported their doctor had given them a FOBT; 3% had received a kit at a health fair. The most common reasons patients reported not being tested was they put it off (48%), did not know it was needed (22%), a doctor did not recommend it (18%) or they hadn't had any problems (15%). Awareness of CRC was high but knowledge was low: 95% said they had heard of CRC but 20% of these could not say what it was. Only 59% had heard of tests to find CRC. Of these, 95% had heard of a colonoscopy and 24% had heard of a FOBT. Attitudes about CRC screening were positive. 88% believed if CRC is found early that their chances of survival were good to very good. 94% believed that having a FOBT was a good way to find colon cancer early. Even though 18% said they were worried a test would find cancer, 91% reported they would want to know if they had CRC. The most common misconception about CRC screening was the age a person should start getting screened - 76% believed it was 0.05) and age (*P* > 0.1) were not associated with altered sensorium. #### Conclusions Although elevated serum osmolality and BUN may contribute to the etiology of altered level of consciousness in DKA, acidosis measured by arterial pH on admission appears to be the strongest determinant of mental status. ### 346 CLINICAL AND MOLECULAR CHARACTERISTICS OF SUCCESSFUL THERAPY OF PATIENTS WITH NEW ONSET DIABETES MELLITUS PRESENTING IN HYPERGLYCEMIC CRISIS A. Gosmanov1, D. Smiley1, G. Robalino1, I. Gerling2, D. Thomason2, G. Umpierrez1 * 1Emory University School of Medicine, Atlanta, GA and 2The University of Tennessee, Memphis, TN* #### Purpose of Study Many African Americans with newly diagnosed diabetes mellitus (DM) presenting with severe hyperglycemia or diabetic ketoacidosis discontinue insulin during follow up. In such patients, a near-normoglycemia remission is associated with improvement in insulin secretion and enhanced insulin signaling in skeletal muscle. In this study, we assessed whether these clinical and metabolic improvements are accompanied by specific patterns in expression of proteins in skeletal muscle both at presentation and during follow up compared to control non-diabetic subjects. #### Methods Used Seven diabetic subjects [mean age 40 yrs, BMI 42 kg/m2, blood glucose (BG) 543 mg/dl, HbA1c 11.8%] underwent percutaneous needle biopsy of the vastus lateralis muscle 2 days after resolution of hyperglycemia/ketosis and at remission. Muscle biopsies from 6 age- and BMI-matched non-DM subjects were used as a control. Commercial antibody microarray was used to assess expression of proteins in muscle. Changes in expression of proteins by 50% or more were considered significant. β-cell function (HOMA-B) was assessed by FSIVGTT. #### Summary of Results After 12 weeks of therapy, 5 patients attained near-normoglycemic remission (BG 109 mg/dl, HbA1c 6.4%). Insulin therapy restored β-cell function in diabetic subjects: HOMA-B 134 ± 36 mU/mM in control subjects and 15 ± 5 mU/mM and 162 ± 45 mU/mM in diabetic patients at presentation and remission, respectively. Compared with control group, at presentation we observed upregulation of PKC isoforms and PI 4-kinase and downregulation of JNK, mTOR, and kinases of inhibitor of nuclear factor κB α and β. These changes persisted despite intensive insulin treatment during follow up suggesting that these proteins are not affected by hyperglycemia or insulin. However, expression of proteins that control cell cycle such as cyclin D1, CDK5, Ca2+ /calmodulin-dependent protein kinase 1 and 2 was 1.5-3-fold higher on remission compared with both control subjects and at presentation. #### Conclusions Near-normoglycemia remission in patients with a history of hyperglycemic crises is associated with improvement in β-cell function and increase in expression of proteins regulating cell cycle. ### 347 METABOLIC SYNDROME INCREASED RISK OF MICROALBUMINURIA IN BLACK AND WHITE YOUNG ADULTS: THE BOGALUSA HEART STUDY L. Ruan1,2, W. Chen1, S.R. Srinivasan1, J. Xu1, G.S. Berenson1 * 1Department of Epidemiology, New Orleans, LA and 2The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China* #### Purpose of Study Microalbuminuria and metabolic syndrome are risk factors for cardiovascular disease. Although numerous studies have shown that microalbuminuria is highly associated with metabolic syndrome, few studies have focused on this relationship in black and white asymptomatic young individuals. #### Methods Used This cross-sectional investigation included 822 white and 345 black subjects, ages 24-44 years, enrolled in the Bogalusa Heart Study. Metabolic syndrome was defined according to guidelines from the National Cholesterol Education Program, Adult Treatment Panel III. Microalbuminuria was defined as urinary albumin to creatinine ratio (ACR) between 3 to 30 mg/mmol. #### Summary of Results The prevalence of microalbuminuria was higher in blacks (12.5%) than in whites (5.6%) (*P* < 0.0001). There was no race difference in the prevalence of metabolic syndrome (24.1% in whites vs 22.0% in blacks, *P* = 0.449). In univariate analyses, subjects with microalbuminuria had significantly higher waist circumference, plasma glucose, triglycerides and blood pressure than those without microalbuminuria in blacks, whites and the total sample. A significantly higher prevalence of microalbuminuria occurred in subjects with metabolic syndrome (13.9%) than those without metabolic syndrome (5.7%) (*P* < 0.0001). Further, the ACR increased significantly by increasing number of components of the metabolic syndrome. In multivariate regression analyses that included age, sex and components of the metabolic syndrome, mean arterial pressure (regression coefficient, β = 0.186, *P* < 0.0001 in whites; β = 0.216, *P* < 0.0001 in blacks) and plasma glucose (β = 0.214, *P* < 0.0001 in whites; β = 0.122, *P* = 0.026 in blacks) were independently associated with ACR. The risk of microalbuminuria increased 3.0 folds (*P* < 0.0001) in whites and 2.7 folds (*P* < 0.005) in blacks among subjects with metabolic syndrome. #### Conclusions These findings suggest that the metabolic syndrome have a significant influence on renal function even in asymptomatic black and white young adults. ### 348 SKIN AUTOFLUORESCENCE IN PRE-DIABETES AND ITS CARDIOVASCULAR DYSFUNCTION J. Chen1, J.A. Stoner2, M. Wu1, T.J. Lyons1 * 1The University of Oklahoma Health Sciences Center, Oklahoma City, OK and 2The University of Oklahoma Health Sciences Center, Oklahoma City, OK* #### Purpose of Study Cardiovascular dysfunction is one of the most severe pathological consequences of diabetes. Previous studies have suggested the damage starts in the pre-diabetes phase. Advanced glycation end products (AGEs) comprise a group of compounds formed through nonenzymatic and oxidative reactions of reducing sugars products with proteins, lipids, or nucleic acids. Animal and human studies demonstrate that AGEs are critically implicated in cardiovascular dysfunction in diabetes. However, clinical studies on the associations of AGEs with cardiovascular dysfunction in pre-diabetes are limited. We hypothesized that in pre-diabetes, cardiovascular dysfunction is associated with increased formation of AGEs. #### Methods Used In a case-control study, we selected, from a larger "parent" cohort study, 32 subjects with impaired glucose tolerance and 32 healthy controls such that age, sex, and body mass index (BMI) were balanced between groups. Cardiovascular function was assessed non-invasively by the Hypertension Diagnostics Inc. CR-2000 instrument. Skin AGE content was determined, also non-invasively, by an investigational new device (SCOUT DS, Veralight, Inc.). Correlations between cardiovascular measures and skin autofluorescence were analyzed by Spearman's rank correlation coefficient and means were compared between groups using a two sample t-test. #### Summary of Results Compared to healthy controls, pre-diabetic subjects had higher skin autofluorescence (*P* = 0.006), which was strongly associated with 2hr post-challenge serum glucose level after adjustment for age among cases and controls combined (p = 0.004). In pre-diabetic females (n = 26), skin autofluorescence was negatively associated with small artery elasticity (*P* < 0.01), stroke volume (*P* < 0.05), stroke volume index (*P* < 0.05), cardiac output (*P* < 0.01), and cardiac index (*P* < 0.05) and positively with systolic vascular resistance (*P* < 0.01). In pre-diabetic males (n = 6), skin autofluorescence was only negatively associated with stroke volume index (*P* < 0.05). #### Conclusions Skin autofluorescence was inversely associated with several cardiovascular function parameters, and these associations may differ by gender. ### 349 GENE EXPRESSION ABNORMALITIES IN SPLEEN LEUKOCYTE TRANSCRIPTOME AND PROTEOME OF YOUNG NOD MICE D.N. Kakoola, J. Wu, N.I. Lenchik, A. Curcio-Brint, I.I. Gerling *University of Tennessee Health Science Center, Memphis, TN* #### Purpose of Study The earliest signs of autoimmune pathology in NOD mice occur at 5 weeks of age. To gain an understanding of the molecular events that lead to initiation of this autoimmune disease we evaluated gene expression abnormalities at mRNA and protein levels in the autoimmune effector cells, spleen leukocytes. #### Methods Used RNA and protein were extracted from spleen leukocytes of NOD mice and two control strains: NON and C57BL/6 at 2 and 4 weeks of age (n = 5 for each age and strain). RNA levels were assayed on expression arrays covering ∼39,000 mouse genes. Protein expression was examined by 2-dimensional gel electrophoresis. #### Summary of Results Statistical analysis of the Affymetrix data by 1-way-ANOVA identified 175 and 189 probesets (genes), with highly significant (*P* < 0.005) expression differences at 2 and 4 weeks, respectively, between at least one of the 3 strains. Hierarchical clustering of these gene lists revealed 51 and 76 of these probesets, as differentially expressed in NOD compared to both control strains (45 lower 6 higher in NOD at 2 weeks; 67 lower 9 higher in NOD at 4 weeks). A one-way ANOVA analysis and hierarchical clustering of the proteome data identified 11 and 8 spots as differentially expressed in NOD mice compared to both control strains, at age 2 and 4 weeks, respectively. We have identified 7 and 6 of the respective number of spots. We subjected the four transcriptome/protein gene lists to pathway analysis ([www.ingenuity.com](http://www.ingenuity.com)). The transcriptome network centered around MYC, TNF, and Ca2+ at age 2 weeks, and around TP53, PRKCA, IL4 and IL15 at age 4 weeks. The networks for the proteome data clustered around MYC, PRKACA and HSPA8* in 2 week old mice, while MYC, PPP5A, CTNNA1, TNF, IL4, hydrogen peroxide as well as HSP90AA1 were central in 4-week old mice. #### Conclusions This data suggests that the basic defects in prediabetic NOD mice involve gene expression abnormalities associated with apoptosis/cellular growth, cellular activation, inflammation, and oxidative stress. Both the transcriptome and proteome data suggests that abnormalities in T-cell differentiation centered on the TH2 cytokine IL4 develop between 2 and 4 weeks of age, before the appearance of autoimmune pathology. ### 350 COMPARISON OF ALENDRONATE AND ZOLEDRONIC ACID IN TREATMENT OF OSTEOPOROTIC MEN O. Sum-Ping1,2, A. Fontenot1,2, A.Y. Chang1, U. Gruntmanis1,2, * 1UT Southwestern Medical Center, Dallas, TX and 2Dallas VA Medical Center, Dallas, TX* #### Purpose of Study Zoledronic acid is a bisphosphanate administered as a once-per-year intravenous infusion which is FDA-approved to treat osteoporosis in women but not men. It is an attractive alternative medication for patients who cannot tolerate orally administered alendronate. However, the effectiveness of zoledronic acid in improving bone mineral density (BMD) in osteoporotic men compared to alendronate has not been previously established. The purpose of this study was to compare the effectiveness of zoledronic acid versus alendronate in improving BMD. #### Methods Used This was a retrospective study of medical records of men with osteoporisis treated with zoledronic acid or alendronate at the Dallas Veterans Affairs Medical Center Endocrine Clinic from 2001 to 2008. Zoledronic acid was administered as a single 4 mg intravenous infusion. Alendronate was prescribed as a 70 mg dose taken orally once per week. Data collected included baseline serum measurements of 25-OH vitamin D, parathyroid hormone, calcium, testosterone and thyroid function tests. Baseline BMDs were measured before initiation of treatment and follow up BMDs were measured one year later. Changes in the BMDs after one year of treatment were compared between the two groups. #### Summary of Results Sixty-four men were identified who were treated with zoledronic acid (n = 26) or alendronate (n = 38). There was no difference in age, baseline thyroid function tests, testosterone, calcium, PTH, 25-OH vitamin D or baseline BMD. There were no significant differences in the changes in total spine or total hip BMD and T score after one year treatment with either zoledronic acid or alendronate. At the trochanteric neck of the hip, there was a significantly greater percent increase in BMD and T score with alendronate than zoledronic acid (BMD: 0.31 ± 6.7% v. -3.0 ± 6.1%, *P* = 0.046; T score: 5.1 ± 13.8% v. - 4.5 ± 10.2%, *P* = 0.03). #### Conclusions Zoledronic acid may be a reasonable treatment alternative to alendronate for men with osteoporosis with no significant differences on BMD at the total hip and total spine at one year. Future studies will need to compare the effects of these treatments over longer periods of time in men. ### 351 ADHERENCE TO THE NATIONAL KIDNEY FOUNDATION OUTCOMES QUALITY INITIATIVE GUIDELINES (K/DOQI) WITH RESPECT TO PTH AND VITAMIN D SCREENING IN CHRONIC KIDNEY DISEASE STAGE 3 PATIENTS J.H. Law1, Y. Kantor2, M. Kumari2, L. Schlanger3, V. Tangpricha2 * 1Emory University School of Medicine, Atlanta, GA; 2Emory University School of Medicine, Atlanta, GA and 3Emory University School of Medicine, Atlanta, GA* #### Purpose of Study To study rates of adherence to the K/DOQI among chronic kidney disease stage 3 (CKD 3) patients attending Diabetes (DM) and Nephrology (Nep) clinics. #### Methods Used We reviewed the records of all pts seen in DM or Nep clinics at the Atlanta VA in 09/2008. For each pt with CKD 3 (GFR <60mL/min/1.73m2 by MDRD), the value and date of the most recent PTH and 25-hydroxyvitamin D value was recorded. A panel of endocrinologists and residents completed surveys regarding PTH screening. #### Summary of Results In Nep clinic, 94% had an annual PTH level, compared to 8% in DM clinics. Among the pts with PTH not at goal, 95% of Nep and 71% of DM pts had a 25-hydroxyvitamin D level determined. Surveys completed by endocrinologists reveal that a majority (83%) are familiar with the K/DOQI and believed they had been checking a PTH at least annually; 80% felt they checked twice a year. Trainee quiz results reveal that only 17% of pgy-1s, 0% of pgy-2s, and 33% of pgy-3s knew the K/DOQI recommendations for PTH screening and 0% of pgy-1s, 17% of pgy-2s, and 17% of pgy-3s knew when to screen for vitamin D deficiency. 93% considered secondary hyperparathyroidism (SHP) a renal disease. #### Conclusions We found that 1 of 4 DM pts have CKD 3 and >90% of these pts do not get annual PTH screening with 62% never having a PTH determination. Survey results suggest several reasons why screening rates outside of Nep clinic are so low, including: the perception of SHP as a renal disease, a lack of emphasis during medical training, and gross overestimations of the actual screening rates. In conclusion, DM clinics see a significant number of CKD 3 pts, and need to initiate strategies to improve PTH screening rates in these pts to prevent or treat SHP. View this table: [Table36](/content/57/1/301/T36) ### 352 PARATHYROIDECTOMY DECREASES SYSTOLIC AND DIASTOLIC BLOOD PRESSURE IN HYPERTENSIVE PATIENTS A.S. Heyliger1, J. Sharma2, C. Weber2, V. Tangpricha3 * 1Emory University, Altanta, GA; 2Emory University, Atlanta, GA and 3Emory University, Atlanta, GA* #### Purpose of Study To determine the effect of parathyroidectomy on systolic and diastolic blood pressure in hypertensive subjects with hyperparathyroidism. #### Methods Used Data was collected retrospectively from medical records from patients undergoing parathyroidectomy between 1997 and 2006. We evaluated changes in serum calcium, parathyroid hormone (PTH) and blood pressure prior to and 6 months after surgery. #### Summary of Results We observed an expected decrease in both parathyroid (PTH) and calcium levels after parathyroidectomy. Hypertensive subjects experienced significant decreases in systolic blood pressure (SBP) from 153.2 ± 11 mmHg to 141 ± 18 mmHg (*P* < 0.001) and diastolic blood pressure (DBP) from 94.8 ± 6.0 mmHg to 83.4 ± 14.0 mmHg. A subgroup analysis revealed that subjects with primary hyperparathyroidism experienced a significant decrease SBP (152.5 ± 10.5mmHg to 140.3 ± 16.2 mmHg) and DBP (94.5 ± 6.8 mmHg to 81.7 ± 10.3 mmHg, *P* < 0.01). No significant changes in blood pressure were observed in secondary or tertiary hyperparathyroidism subjects. #### Conclusions This retrospective study suggests that parathyroidectomy in hypertensive subjects with primary hyperparathyroidism may be beneficial in reducing blood pressure. The presence of hypertension may be another indication for parathyroidectomy in these patients. ### 353 OX-LDL IMMUNOCOMPLEXES ARE IMPLICATED IN DIABETIC RETINOPATHY M. Wu1, Y. Chen1, S.A. Abdel-samie2, K. Wilson1, M.E. Boulton3, J. Ma1, G. Virella2, M.F. Lopes-Virella2, T.J. Lyons1 * 1University of Oklahoma Health Sciences Center, Oklahoma City, OK; 2Medical University of South Carolina, Charleston, SC and 3University of Florida, Gainesville, FL* #### Purpose of Study Extravasated and oxidized low-density lipoprotein (LDL) have been identified in the retina in diabetes, and implicated in diabetic retinopathy (DR) in our recent cell culture and immunohistochemical studies. Oxidized LDL may be immunogenic, resulting in the formation of ox-LDL immunocomplexes (LDL-IC) containing IgG - and such complexes have recently been implicated in atherogenesis. In the current study, we investigated whether LDL-IC are associated with the initiation and progression of DR. #### Methods Used Immunostaining of ox-LDL and IgG was performed in retinal sections from four different groups of human subjects: non-diabetic; (Type 2) diabetic without clinical retinopathy; diabetic with moderate non-proliferative diabetic retinopathy (NPDR); diabetic with proliferative diabetic retinopathy (PDR). In cell culture studies, induction of apoptosis by human LDL-IC in human retinal capillary pericytes (HRCP) was assessed. #### Summary of Results Ox-LDL and IgG was absent in non-diabetic subjects but present in all three diabetic groups, increasing with severity of DR. Merged images revealed co-localization of ox-LDL and IgG. Human LDL-IC (50 mg/L) significantly attenuated retinal capillary pericyte viability compared to effects of rabbit LDL-IC and ox-LDL (however ox-LDL also triggered apoptosis, but at higher concentrations). The apoptotic mechanisms were related to PARP pathways and caspase cascade activation, but were independent of reactive oxygen species levels. #### Conclusions The data suggest a potentially important role for LDL-IC, formed after extravasation and oxidation of LDL in the retina, in promoting an early feature of DR, pericyte loss by apoptosis. ### 354 HYPERGLYCEMIA DURING TOTAL PARENTERAL NUTRITION (TPN): AN IMPORTANT MARKER OF MORTALITY IN ICU AND NON-ICU PATIENTS G. Umpierrez, R. Spiegelman, E. Lin, C. Gatcliffe, D. Smiley, M. Luo *Emory University SOM, Atlanta, GA* #### Purpose of Study Hyperglycemia is a recognized complication of TPN therapy. The prevalence of TPN-induced hyperglycemia and its impact on clinical outcome, however, are not known. We determined i) the prevalence of TPN-induced hyperglycemia (BG >180 mg/dl), ii) the impact of hyperglycemia on survival after adjusting for known prognostic factors, and iii) whether BG value prior to initiation of TPN and/or highest BG within 24-hours of TPN are predictive markers of in-hospital mortality. #### Methods Used We reviewed the medical records of 163 med-surgery patients treated with TPN (age: 52 ± 19 yr, 106M/57F, BMI: 27 ± 8 kg/m2, known history of DM: 37%) admitted to Grady Memorial Hospital in 2006. #### Summary of Results Hyperglycemia (BG>180 mg/dL) was present in 122 (75%) patients during TPN, of whom 58 patients (35%) had known DM and 105 patients (65%) had TPN-induced hyperglycemia. TPN-induced hyperglycemia was associated with higher in-hospital mortality (36%) when compared to diabetics (26%) and patients with normoglycemia (BG ≤120) (9%) (*P* = 0.020). We found a strong association between BG levels before and during TPN and hospital mortality. The mortality rate of a BG <120 mg/dl or >180 mg/dl prior to TPN was 12% and 35%, p:0.010; maximum BG within 24 hr of TPN: 13% and 43%, *P*:0.0007; and during TPN: 18% and 42%, p:0.038. In multivariate analysis, mortality odds ratio for a pre-TPN BG >150 mg/dl: 6.073 (95% CI: 1.494, 24.684), maximum BG within 24 h >180 mg/dl: 3.396 (1.016, 11.354), and during TPN BG >180 mg/dL the OR: 1.86, p: 0.05). TPN patients who died had a higher Apache II score 13.6 ± 7.5 v. 9.6 ± 6.4 (*P* = 0.004), were older (59 ± 17 v. 50 ± 19, *P* = 0.010), and more likely to be admitted to an ICU (*P* = 0.008). Increased mortality was not associated with the amount of total calories given or a past history of DM. #### Conclusions Hyperglycemia during TPN therapy is common and an important marker of mortality in patients with and without a history of diabetes. Patients with TPN-induced hyperglycemia had a significantly higher mortality rate than patients with normoglycemia. Blood glucose values prior to TPN and the highest BG values within 24 hours of TPN are the best predictors of mortality. Thus, early and aggressive intervention to prevent and correct hyperglycemia may improve clinical outcome during TPN. ## **Gastroenterology and Clinical Nutrition II Concurrent Session** 1:00 PM Saturday, February 14, 2009 ### 355 ROLE OF INTERLEUKIN-8 RECEPTORS IN GUT MUCOSAL DEVELOPMENT T. Kim1, J. Kidd1, R.A. Dimmitt1, R.K. Singh2, A. Maheshwari1 * 1UAB, Birmingham, AL and 2UNSOM, Omaha, NE* #### Purpose of Study We have shown previously that ELR + CXC chemokines such as interleukin-8 (IL-8) are expressed in amniotic fluid, milk, and in fetal intestinal epithelial cells (IECs). IL-8 increases IEC proliferation, migration, and prevents IEC apoptosis in vitro. IL-8 also recruits monocytes to the gut mucosa, where these cells differentiate into macrophages. In this study, we investigated the role of ELR + CXC chemokine signaling in intestinal mucosal development. We hypothesized that mice lacking IL-8 receptors (CXCR2) will have morphometric abnormalities in the crypt-villus axis and fewer macrophages in the lamina propria. #### Methods Used Intestines were harvested from wild-type, CXCR2 + /-, and CXCR2-/- mice on fetal day 18.5 (E18.5), and at postnatal age 4 and 12 wks. Villus height, villus area, lamina propria (LP) height, LP area, number of LP cells, crypt depth, crypt area, IEC diameter, IEC height, and IEC area were measured. IEC proliferation was measured by immunohistochemistry (proliferating cell nuclear antigen, PCNA). Macrophages were enumerated by immunofluorescence for the marker F4/80. #### Summary of Results Villi in CXCR2-/- mice were narrower than WT (villus area 14973 ± 968 μm2 in CXCR2-/- adult mice, 16358 ± 2470 μm2 in CXCR2 + /-, and 22703 ± 682 μm2 in WT; *P* < 0.05). These narrow villi enclosed a smaller lamina propria (2642 ± 217 μm2 in CXCR2-/-, 4766 ± 653 μm2 in CXCR2 + /-, 5522 ± 257 μm2 in WT; *P* < 0.05) and fewer LP cells (28 ± 8 cells/villus in CXCR2-/-, 49 ± 5 in CXCR2 + /-, and 70 ± 5 cells/villus in WT; *P* < 0.05). The crypts in CXCR2-/- mice were also narrower and smaller in area than WT mice (2057 ± 105 vs. 3808 ± 215 μm2 in adult CXCR2-/- and WT mice, respectively). Crypt area correlated inversely with the number of crypt nuclei and with PCNA immunoreactivity (6 ± 2 positive nuclei per crypt in CXCR2-/- mice vs. 12 ± 3 nuclei in WT mice; *P* < 0.05). The number of F4/80 macrophages per villus in CXCR2-/- mice was also lower than WT mice. #### Conclusions ELR + CXC chemokine signaling through CXCR2 plays an important role in intestinal development. ELR + CXC chemokines are better-known for their role as neutrophil chemoattractants and small molecule inhibitors of CXCR2 are under development as candidate anti-inflammatory agents. Our findings indicate the need for rigorous pre-clinical safety studies for these agents in neonates and young children. ### 356 EARLY INTRODUCTION OF A DEFINED SET OF NON-PATHOGENIC BACTERIA PROMOTES VILLUS DEVELOPMENT IN GERM-FREE ANIMALS A. Maheshwari1, D. He1, A.R. Kurundkar1, T.R. Schoeb2, S.K. Jain3 * 1UAB, Birmingham, AL; 2UAB, Bhm, AL and 3UTMB, Galveston, TX* #### Purpose of Study In premature infants, gut bacterial colonization is delayed because of prolonged nil per os (NPO) periods and the use of broad-spectrum antibiotics. The germ-free state is associated in rodents with abnormal morphological and functional development of the intestinal mucosa. We investigated whether gut mucosal abnormalities seen in germ-free animals can be prevented by early introduction of a limited but well-defined set of non-pathogenic bacteria. #### Methods Used Germ-free (GF) B6 mice were maintained in sterile steel isolators and fed a sterile diet. Some pups were colonized on day 2 with the altered Schaedler flora (ASF), which includes 8 bacteria (2 lactobacilli, 1 Bacteroides, 3 Clostridia, 1 Flexistipes and ASF 500). Controls included mice reared under conventional conditions. Mice were euthanized at 6 and 12 wks. Intestinal villus height, villus area, lamina propria (LP) height, LP area, number of LP cells, crypt depth, crypt area, IEC diameter, IEC height, and IEC area, were measured (Metamorph software). Immunostaining was used to measure crypt cell proliferation (proliferating cell nuclear antigen, PCNA) and to enumerate macrophages (marker F4/80). #### Summary of Results GF mice had narrower villi (area 30518 ± 1430) than conventionally-reared mice (24087 ± 2031 μm2, *P* < 0.05) with a smaller lamina propria (LP, area 14251 ± 1267 vs. 5134 ± 850 μm2, *P* < 0.05) and fewer LP cells (83 ± 9 and 29 ± 2 cells/villus, *P* < 0.05). In ASF-colonized mice, villus area was partially corrected to 27856 ± 2012 μm2 and LP area to 8102 ± 526 μm2. The number of LP cells increased to 66 ± 3 cells/villus. However, ASF mice had reduced villus height and crypt depth/crypt area. The number of LP macrophages in ASF mice was intermediate between GF and conventional mice. The smaller crypt area in ASF animals was associated with decreased crypt cell proliferation. #### Conclusions Early introduction of a limited set of non-pathogenic bacteria may prevent some of the mucosal abnormalities seen in the germ-free developing intestinal mucosa. Villus development in ASF-colonized mice was better than GF mice but was not completely restored as in conventionally-reared animals, suggesting that larger, more representative gut bacterial ecosystems may be even more effective in normalizing gut mucosal development. ### 357 PREVENTING COMPLICATIONS IN VLBWI IN THE NICU: SHOULD MOTHER'S OWN MILK ROUTINELY BE SCREENED FOR BACTERIA? A. Willeitner *OUHSC, Oklahoma City, OK* #### Purpose of Study Mother's own milk (MOM) is the food of choice for preterm infants. However it is, by nature, not a sterile fluid. Routine bacterial sampling of mother's own milk has been advocated. We present a prospective, observational study to evaluate the efficacy and risk-benefit ratio of this practice. #### Methods Used A policy of weekly screening of mother's own milk was implemented for all infants under 1500 g of birth weight (VLBWI) in a level III NICU over a period of 12 consecutive months. The impact of the measure on the rate of systemic bacterial infection, gastrointestinal disturbances, and breastfeeding rates were compared with those during the preceding 12-month period. #### Summary of Results After routine MOM screening was implemented, the amount of MOM fed was significantly reduced: A substantial portion of MOM was either pasteurized and then fed or discarded per ID recommendations, based on the results of bacterial cultures (see table). Although the numbers were small, there was no trend towards reduced mortality or gastrointestinal morbidity while routine MOM screening was performed. #### Conclusions The practice of routine bacterial screening of MOM had a negative impact on the amount of MOM fed to preterm infants and conversely led to increased feeding of formula. The practice of bacterial testing on MOM did not reduce rates of systemic infection or gastrointestinal complications. While larger randomized trials would be needed for a definitive evaluation, these preliminary results do not support the implementation of routine bacterial screening of MOM in the NICU. View this table: [Table37](/content/57/1/301/T37) Outcomes of routine MOM sampling for bacteria ### 358 A SURVEY OF PROPOFOL CONSCIOUS SEDATION FOR GASTROINTESTINAL PROCEDURES K.E. Occhipinti, S.E. Hendon, J.A. Di Palma *University of South Alabama, Mobile, AL* #### Purpose of Study This study examined the use of propofol for conscious sedation during gastrointestinal procedures. Efficacy and safety of propofol regimens have been established. This work focused on outcomes and sequelae in clinical use. #### Methods Used This was a retrospective review of procedures performed in the Division of Gastroenterology from April 2005 to March 2008. The study group consisted of consecutive patients who received conscious sedation using propofol. A representative control group was compiled of patients during a similar period who had sedated procedures without propofol. Charts were reviewed for demographics, procedural details, sedation regimen, and adverse events. #### Summary of Results The study group consisted of 689 cases and the control group consisted of 706 cases. All procedures were performed by gastroenterology faculty and fellows without anesthesiologist assistance. The study group typically received a regimen that included a narcotic (fentanyl or meperidine), sedative (midazolam or diazepam) and propofol titrated by the gastroenterology physician. The control group had varied regimens, mostly a narcotic (fentanyl and meperidine) and sedative (midazolam). The procedures performed in both groups were EGD, colonoscopy, small bowel enteroscopy, flexible sigmoidoscopy, ERCP and PEG placement. There were adverse experiences reported in 52 cases (7.3%) in the control group and 27 cases (3.9%) in the propofol group, with more than 1 event per patient in some instances in this group. There were no deaths, no permanent clinical sequelae as a result of sedation nor was endotrachael intubation required in either group. Bag mask ventilation was used in 5 of the propofol group. Hypoxia was seen in 20 (2.9%) in the propofol group and 39 (5.5%) in the control group. Bradycardia was reported in 5 propofol and 4 control subjects. Tachycardia was reported in 2 control subjects. One propofol and 4 control subjects had experienced hypotension and 1 propofol subject experienced hypoventilation. Inadequate sedation was noted in 1 propofol and 2 control subjects. Non-sedative complications included 1 propofol subject with a perforation and 1 control subject with bleeding after polypectomy. #### Conclusions This survey showed similar outcomes and sequelae reported after regimens with and without propofol used for gastrointestinal conscious sedation. ### 359 FENOFIBRATE INDUCED HEPATIC TOXICITY: A CASE REPORT AND REVIEW OF THE LITERATURE H. Shabaneh AlTamimi *Texas Tech University HSC, Lubbock, TX* #### Purpose of Study Fenofibrate is a synthetic phenoxy-isobutyric acid derivative first synthesized in 1975 and belongs to clofibrate and gemfibrozil family It is currently used to treat all classes of hyperlipidemia and is highly effective in reducing serum triglycerides, total cholesterol and LDL-C and in raising HDL-C level. Hepatic injury is extremely rare and to our knowledge, only 11 cases were described in the French, Italian or Spanish literature and one case was reported from Taiwan. Here, we report the first case of fenofibrate induced acute cholestatic hepatitis in the United States. A 56-year old female was referred with a one month history of gradually worsening jaundice, pruritis and tea-colored urine associated with anorexia and 13 pound weight loss. She had a history of type 2 diabetes mellitus and systemic hypertension for 15 years and hyperlipidemia for 5 years and was maintained on metformin and amlodipine. Fenofibrate at a dose of 145 mg daily was prescribed 4 weeks prior to the onset of her current symptoms. The patient denies any history of blood transfusion, illicit drug or alcohol use. Physical examination showed normal vital signs, deeply icteric sclera and skin with itching marks all over but no stigmata of chronic liver disease. The rest of her examination was unremarkable Laboratory data showed normal hepatic profile from a laboratory data obtained 3 months ago. Current laboratory data showed a total bilirubin (TB) of 9.9 mg/dl (normal range0-1 mg/dl) with a mainly elevated direct proportion (DB) of 7.3 mg/dl (0-0.2 mg/dl), alanine aminotransferase (ALT) of 81 IU/L(0-41 IU/L), aspartate aminotransferase (AST) of 43 IU/L (0-32 IU/L), alkaline phosphatase of 183 IU/L (35-129 IU/L), gamma-glutamyl transferase (γGT) of 871 IU/L (4-50 IU/L). Prothrombin time was 11 seconds (control 12 seconds), albumin 3.4 g/l (3.5-5.3 g/l), hepatitis profile was negative, serum ceruloplasmin was 40 mg/dl (18-53 mg/dl), alpha-1 antitrypsin 155 mg/dl (90-200 mg/dl), antinuclear, antiactin and antimitichondrial antibodies were negative. Iron studies were normal. CA 19-9 15.2 U/ml(0.6-35 U/ml)Abdominal ultrasonography showed a normal liver architechture and normal biliary tree.A magnetic resonance cholangiopancreatography showed a slightly thickened gallbladder wall but was otherwise unremarkable. A percutaneous liver biopsy showed bile stasis in pericentral and periportal areas, hyperplasia of Kupffer cells, minimal steatosis, mild mononuclear inflammatory cell infiltrate, occasional apoptotic bodies. The trichome stain showed showed increased collagen deposition in the spaces of Disse. The reticulin stain showed focal and minimal thickening of the liver plates (see figure1) Based on a high index of suspicion, fenofibrate was held, even before liver biopsy was performed. The patient was given an antipruritic agent, cyproheptadine and sent home. On follow up 6 weeks later, her symptoms had completely resolved. Laboratory data at that time showed a slightly raised total bilirubin (1.5 mg/dl), alanine aminotransferase was elevated at 89 IU/L. At 12 weeks follow up, she was still asymptomatic and her ALT, AST, Alkaline phosphatase and total bilirubin were all completely in the normal range **Methods Used:**NA **Summary of Results**NA **Conclusions**NA ### 360 SEROSAL ELECTROGASTROGRAM DEMONSTRATES REPRODUCIBLE PHYSIOLOGIC CHARACTERISTICS DURING ENDOSCOPIC MANEUVERS ON DRUG-REFRACTORY GASTROPARETICS G.L. Montague3, R. Schmieg2, C. Lahr2, D. Spree1, W. Johnson4, T. Abell1 * 1University of Mississippi Medical Center, Jackson, MS; 2University of Mississippi Medical Center, Jackson, MS; 3University of Mississippi, Jackson, MS and 4University of Mississippi Medical Center, Jackson, MS* #### Purpose of Study Controversy over the significance of the Electrogastrogram (EGG) has continued to limit its clinical usefulness. We investigated the origins and significance of directly recorded EGG signals in response to physiologic maneuvers in patients with drug-refractory gastroparesis (GP). #### Methods Used 16 female and 3 male GP patients underwent permanent gastric electrical stimulation (GES) implantation. Intraoperatively, EGG recordings were performed sequentially for at least five minutes during stomach partial inflation (baseline), maximal insufflation(R1), desufflation (D1), re-insufflation (R2), and repeat desufflation (D2). EGG recordings were analyzed qualitatively for rhythm (regular vs. irregular) and amplitude (Equal or UnEqual) and quantitively for mean frequency (Freq) in CPM and amplitude (Amp) in mV as well as the Freq/Amp ratio (FAR). Results were compared for differences from baseline frequency (base to R1). #### Summary of Results EGG recordings demonstrated more regularity and equal amplitude in periods D1 and D2. There was an initial decrease then stabilization in Freq. In the insufflation and desufflation periods, a progressive decrease in Amp was noted, along with a gradual increase then stabilization in FAR (See Table). #### Conclusions Intraoperative serosal EGG recordings provoked by physiologic maneuvers show reproducible characteristics in gastric electrical activity. EGG recordings of the relaxed stomach display a more regular rhythm and equal amplitude than in the distended stomach. Maintenance of FAR both when relaxed and distended may be a measure of gastric homeostasis. Standardization of the EGG in terms of gastric distention may be needed for accurate physiologic interpretation. View this table: [Table38](/content/57/1/301/T38) ### 361 GASTRIC ELECTRICAL STIMULATION AND SACRAL ELECTRICAL STIMULATION: ARE 2 DEVICES BETTER THAN 1? J.T. McNeese1, G.L. Montague2, D. Spree1, C.J. Lahr3, T.L. Abell1 * 1University of Mississippi Medical Center, Jackson, MS; 2University of Mississippi, Jackson, MS and 3University of Mississippi Medical center, Jackson, MS.* #### Purpose of Study Gastric Electrical Stimulation (GES) is available as a Humanitarian Use Device for gastroparetic patients and is effective in reducing gastrointestinal symptoms. We have previously shown that patients with upper gastrointestinal motor disorder often have co-existing abnormalities of the lower gastrointestinal tract and genitourinary system. In this study, we compared the results of therapy with GES and SES in 37 patients implanted with both devices. #### Methods Used Patients were 35 f, 2 m, mean age of 44 years-old, with gastroparesis as well as bladder or other pelvic floor dysfunction. 33 patients received their GES before SES. 4 patients had post-surgical gastroparesis, 5 had diabetes mellitus (type I or II), and the rest had idiopathic gastroparesis. Patients were evaluated at baseline, latest, and follow-up (median 4 yrs GES and 2 years SES) using standardized scores of upper GI (UGI: 0-4, UGITSS max 20), lower GI (LGI: 0-3, LGITSS, max 9) and GU (GU: 0-3, UTSS, max 12) function as well as quality of life (QOL) before and after GES and SES. Results were compared by t-tests and reported as mean ± SE. #### Summary of Results In this group of 37 patients, combined gastric and sacral electrical stimulation improved UGI and LGI symptoms (See Tables 1 & 2). Urinary symptoms also improved (UTSS score before = 8.1 ±.06 vs after = 2.6 ± 0.5, *P* < 0.001). Quality of life scores improved significantly for each stimulator individually as well as the two stimulators combined (from -2.3 ± 0.3 to 1.6 ± 0.3, *P* < 0.001). #### Conclusions A combined treatment of GES and SES appears to be safe and effective for patients with gastroparesis, bowel problems, and bladder dysfunction. View this table: [Table39](/content/57/1/301/T39) Upper GI Symptoms View this table: [Table40](/content/57/1/301/T40) Lower GI Symptoms ### 363 PERMAMENT GATRIC ELECTRICAL STIMULATION IMPROVES SYMPTOMS OF POST-SURGICAL DISORDERED GASTRIC EMPTYING R.C. Humble3, R.E. Schmieg2, J.M. Runnels1, T.L. Abell1 * 1University of Mississippi Medical Center, Jackson, MS; 2University of Mississippi Medical Center, Jackson, MS and 3University of Mississippi Medical Center, Jackson, MS* #### Purpose of Study Gastric Electrical Stimulation (GES) has successfully treated disordered gastric emptying (DGE) from diabetic, post-viral, and idiopathic etiologies. The utility of GES in DGE due to post-surgical etiologies has not been previously defined. We hypothesized that GES would significantly improve gastric symptoms and physiologic gastric emptying in patients with post-surgical DGE. #### Methods Used Adult patients (n = 36, 5M/31F) with dietary and pharmacologic refractory post-surgical DGE characterized by chronic nausea and postprandial emesis underwent placement of a permanent GES system. Quantitative symptoms (nausea, vomiting, early satiety, bloating, abdominal pain, scored 0-4; total symptom score summed, 0-20) and measures of gastric emptying (of a low fat meal) were recorded at baseline and after permanent GES placement (permGES) (6-48 month postoperatively). Data from symptom measurements are reported as mean ± standard error of mean. Statistical analysis was performed using Student's t-test. Improvements in gastric empting were reported according to the differential pathology (rapid or delayed) common to this etiological subset. #### Summary of Results Patients with post-surgical DGE who underwent permanent GES implantation had significant improvement in DGE symptoms on long-term postoperative follow-up. Furthermore, 6 of the 11 patients whom were previously Delayed, and 3 of the 5 patients whom were previously Rapid, exhibited sustained improved gastric emptying (toward normal) after permGES placement. #### Conclusions In patients suffering from symptomatic refractory post-surgical disordered gastric emptying, permanent placement of gastric electrical stimulation system should be considered a viable option for symptom control. View this table: [Table41](/content/57/1/301/T41) DGE Symptoms Before and After PermGES ## **Health Care Research Concurrent Session** 1:00 PM Saturday, February 14, 2009 ### 364 SHOULD A CARDIOLOGIST BE THE PRINICIPAL ATTENDING OR THE CONSULTANT FOR CARDIOVASCULAR DISEASE ADMISSIONS? G. Everett1,2,3, N. Uddin3 * 1Florida Hospital Medical Center, Orlando, FL; 2Orlando Health, Orlando, FL and 3University of Central Florida, Orlando, FL* #### Purpose of Study We wanted to determine whether a cardiologist is more cost-effective in the role of principal attending physician or the role of consultant to a general internist or hospitalist for cardiovascular disease admissions. #### Methods Used A five year retrospective cohort study of 15103 subjects from 11 high volume cardiovascular diagnosis groups (APRDRG) were evaluated for hospital cost, length of stay (LOS), readmissions and mortality over a 57 month period ending in 2005. The 11 APRDRGs were subdivided into 7 that included a procedure (PROC) and 4 without a procedure (NPROC). After multivariable statistical adjustment for severity and demography, cardiologists' patients were compared to general internists' or hospitalists' patients for cost effectiveness for the role of principal attending physician. The setting was a large, urban, community teaching hospital and included patients from 103 internists, 66 hospitalists and 70 cardiologists. #### Summary of Results Baseline characteristics of patients differed in that cardiologists had fewer non-white patients, a higher proportion of PROC APRDRGs, and lower severity level compared to hospitalists or internists. Hospitalists and internists consulted a cardiologist 81-91% and 93-94% for NPROC and PROC cases respectively. Cardiologists consulted hospitalists or internists 8-2% and 8-5% for NPROC and PROC cases respectively. Hospital cost (COST) was 11% and 15% higher for internists and hospitalists, respectively, compared to cardiologists for NPROC diagnoses. COST was 19% and 21% higher for internists and hospitalists, respectively, than cardiologists for PROC diagnoses. LOS did not significantly differ among the groups for NPROC diagnoses but were 38% and 35% higher for internists and hospitalists, respectively, compared to cardiologists for PROC diagnoses. There were no statistically significant differences among the physician groups for mortality or 30-day readmissions #### Conclusions For the high volume cardiovascular diagnoses studied, cardiologists had equivalent mortality and readmission rates but lower COST and LOS than internists or hospitalists when acting as the prinicipal attending physician. ### 365 ASSESSMENT OF MEDICATION MONITORING ERRORS IN A PRACTICE BASED RESEARCH NETWORK C. Litvin, S. Ornstein, A. Wessell, R. Jenkins, P.J. Nietert, L. Nemeth, H. Rose *Medical University of South Carolina, Charleston, SC* #### Purpose of Study Failing to monitor medications frequently leads to adverse drug events and hospitalizations, yet little is known about the prevalence of these errors in the outpatient setting. Prior estimates have largely been based on administrative data. The purpose of this study was to assess the frequency of laboratory monitoring errors within a practice based research network using data extracted from the electronic medical record (EMR). #### Methods Used The Practice Partner Research Network (PPRNet) maintains a longitudinal database extracted from the EMRs (Practice Partner®) of participating primary care practices. 9 indicators were developed based on expert panel recommendations to reflect whether patients received appropriate laboratory monitoring of commonly prescribed drugs, including ACE-Inhibitors and ARBs, diuretics, digoxin, NSAIDS, oral anticoagulants and metformin. Each indicator was defined as the proportion of patients with an active prescription for the specified medication who received the appropriate laboratory monitoring. All measures were incorporated over a one year time frame. #### Summary of Results The monitoring indicators were applied to a total of 52,992 patients. 82% of patients who were prescribed drugs requiring at least annual creatinine monitoring had the appropriate monitoring. Potassium was monitored when indicated in 84% of patients. 73% of patients prescribed anticoagulants received indicated hematologic monitoring. Amongst all practices, median performance by indicator ranged from 74% (measure of platelet count in past year for patients prescribed an oral anticoagulant) to 90% (measure of serum creatinine in past year for patients prescribed metformin). Appropriate laboratory monitoring occurred in 82% of eligible patients. #### Conclusions The frequency of medication monitoring errors can be assessed using data extracted from the EMR. Rates of laboratory monitoring were higher than previous estimates of errors derived from administrative data. As data was obtained from practices participating in a network focused on benchmarking and quality improvement, these conclusions may be limited. Nevertheless, although roughly 5 out of 6 patients in these practices received appropriate laboratory monitoring, opportunities still remain for improving medication safety in the primary care setting. ### 366 EFFICACY OF ERYTHROPOIETIN STIMULATING AGENT (ESA) ADMINISTRATION ALTERNATIVES IN MAINTAINING TARGET HEMOGLOBIN IN AN IMPOVERISHED NONCOMPLIANT HD POPULATION S. Lam, L. Zsom *University of MS Medical Center, Jackson, MS* #### Purpose of Study Clinical response to ESA may be dependent on the route of administration. Countries where ESA are administered subcutaneous (SC) report substantially lower ESA dosages. Following a recent policy making SC ESA the primary route of delivery at our HD center, we monitored the level of compliance and the effects of this change. #### Methods Used In our largely African American HD population with high rates of noncompliance (16% substance abuse, 25-30% multiple missed treatments) and co-morbidity (Diabetes 57%, Vascular disease 57%, hyperlipidemia 91%, HIV/AIDS 6%), we implemented a new anemia management policy in our HD unit. During November, 2007, all patients were switched from intravenous (IV) to SC erythropoietin. For evaluation of the efficacy of the policy change, we compared ESA utilization and anemia-related outcomes in a 3-month period prior to (baseline months) and subsequent to (target months) the policy change. #### Summary of Results For the 126 patients converted from IV to SC, 91% of patients complied with SC ESA administration through the end of the target period. None of these patients reported discomfort related to the switch. Mean Hbg remained stable (11.51.26 mg/dl at baseline vs 11.61.16 mg/dl target period NS) despite a higher ratio of incident patients (7% at baseline vs 11% target period). Interestingly, more patients remained at target (Hgb11 mg/dl: 69.4% baseline vs 76.1% target period) on SC ESA with an average weekly dose of ESA that was lower than IV (294.3U/kg/week at baseline vs 198.3 U/kg/week target period). #### Conclusions In our HD unit, SC administration of ESA can maintain the Hbg in a desired target range with dose reduction by 33% of SC versus that of IV. High compliance with SC ESA could be achieved even in a population with high rates of missed treatments. View this table: [Table42](/content/57/1/301/T42) Summary ### 367 ACCESS TO EARLY DENTAL CARE: AN INITIAL STEP TO DENTAL HEALTH C.K. Mitchell, A.Y. Kamdar, J.A. Theriot, S.M. Franco *University of Louisville, Louisville, KY* #### Purpose of Study Tooth decay is the most common chronic childhood disease. Children from low-income households have higher incidence of dental caries and more unmet needs than their higher-income counterparts. Utilization of dental services for children on Medicaid remains low. The objective of this study was to improve access to preventive dental care in the first two years of life. Our hypothesis is that offering same day dental visits during a Well Child Visit (WCV) in a clinic with both medical and dental services will significantly increase dental visits in this population. #### Methods Used The Children and Youth Project is an urban, university-affiliated pediatric clinic with dental services on-site serving an indigent population. Children 12 - 24 months presenting for WCV from 08/2007 through 06/2008 on Mondays or Tuesdays were invited to participate in expedited medical/dental checkups, while those with WCV Wednesday through Friday served as controls. Parents from both groups completed a questionnaire regarding weaning and use of a toothbrush. All were counseled on the importance of dental checkups for this age. Our historical rate of dental visits from 1995 - 2006 for this age group (33%) was used for comparison. #### Summary of Results Of the 799 eligible children, 313 (39%) agreed to participate in the study. Medicaid insurance covered 89.5% (271) of the participants. Only 33 (10.5%) of the participants had no dental insurance, divided equally by group. Dental visits occurred in 52.5% (63 of 120) of the study group and in 33.7% (65 of 193) of the control group (Chi-square 10.844, df = 1, *P* = 0.001). Compared to the historical rate of dental visits, the study group, but not the control group, had significantly higher rates of dental visits (t = 4.26, df = 119, *P* < 0.001). Expedited MD/DMD visits occurred in 42.5% (51 of 120) of the study and 16% (31 of 193) of the control groups (Chi-square 13.266, df = 1, *P* < 0.001). #### Conclusions Even when medical and dental services are offered in the same facility, low utilization of dental services for lower-income children is common. Expedited medical and dental checkups during well child visits of 12 - 24 month old children significantly improved access to early dental care. ### 368 EXPRESSED PREFERENCE FOR THE EMERGENCY ROOM AS PRIMARY SOURCE OF CARE IN AN UNDERSERVED POPULATION R.D. Foreman1, C. Voelkel2, M.I. Arrieta1,2 * 1University of South Alabama, Mobile, AL and 2University of South Alabama, Mobile, AL* #### Purpose of Study The overburdening of hospital emergency departments by patients with non-emergent conditions has been well documented. Using qualitative methods, we sought to explore the reasons persons may seek care at the emergency department for such conditions. #### Methods Used Participants were recruited via purposeful sampling from an economically disadvantaged, predominantly minority population residing within the University of South Alabama Medical Center (USAMC) service area in Mobile, AL. USAMC is a 130 bed tertiary care teaching hospital. Forty-two focus groups were conducted with 246 participants at six community locations. Focus groups were audio-taped and verbatim transcripts analyzed for emerging themes by research team members not involved in data collection. #### Summary of Results The majority of participants were female, African American and self-paid for medical services. Reasons participants actively chose to seek primary care at the USAMC emergency department included: 1) receiving diagnostic tests and procedures not available in the primary care setting; 2) immediate attention for the problem (i.e., not having to wait to get an appointment in primary care); 3) receiving care without having to pre-pay (i.e., patients were billed for services, but bills could be ignored); and 4) guaranteed medical care, regardless of insurance status. These reasons-quality, accessibility and cost-put emergency departments, which legally cannot turn patients away, in a difficult position when considering how to divert patients to primary care. #### Conclusions It may be necessary for hospitals to partner with local federally qualified health centers and other primary care providers to assure patients they have a source of reasonably priced care in a timely manner and to put in place effective referral mechanisms. Community health education programs, particularly those that involve community health advocates, may also succeed at getting information to community members regarding the importance of seeking services in the primary care setting. Finally, an attached skilled nursing unit may also provide an accessible on-site solution to patients eager to receive immediate care. ### 369 PEDIATRIC PALLIATIVE CARE STAFF KNOWLEDGE: CONTINUING ASSESSMENTS A. Brin1, B.S. Carter2, B. Donaghey3, J. Mulder4, M. Gilmer3 * 1Alive Hospice, Nashville, TN; 2Vanderbilt University Medical Center, Nashville, TN; 3Vanderbilt University, Nashville, TN and 4Faith Hospice, Grand Rapids, MI* #### Purpose of Study Pain and symptom management is an integral part of pediatric palliative care (PPC), but limited research relates any evidence-based knowledge of healthcare providers caring for children. The purpose of this study was to assess PPC knowledge of interdisciplinary healthcare team members over time, identify areas of clinical strengths, and identify staff needs in caring for children with life-limiting/threatening conditions (LTC). #### Methods Used A cross-sectional convenience sample of interdisciplinary hospital-based healthcare providers caring for children with LTC at Vanderbilt was surveyed in 2002, and again in 2007 after implementing an interdisciplinary PPC team. Respondents (N = 133 in 2002, N = 168 in 2007) completed a 25 question survey, indicating their knowledge and experiences in caring for children with LTC. The survey was adapted from a published tool by Ross, et al. in 1996 entitled "The palliative care quiz for nursing (PCQN)" (J. Advanced Nursing, 23:126-137) and in 2007 targeted neonatal and pediatric ICU staff. Two open-ended questions asked respondents to describe their opportunities to provide PPC services and their own perceived support needs. #### Summary of Results Responses came from nurses (75%) and physicians (>50% of targeted residents and attending physicians). Significant improvement was seen in the active integration of PPC precepts into care for children at the end-of-life (8% in 2002 vs. 64% in 2007). However, providers' lack of understanding pediatric palliative care compatibility with cure oriented life-extending care in the ICU environment was evident. #### Conclusions Results demonstrate a need to provide ongoing PPC education for healthcare providers, especially in the ICU environment. Further examination of ICU provider-perceived barriers for early PPC integration requires study. There is a need to provide interdisciplinary educational interventions as a foundation for scientific knowledge, skills, and ethical understanding of pediatric palliative care. This survey provided useful data for baseline staff knowledge assessment, program evaluation, and continuing education needs focused on the PPC provision. ### 370 PSYCHOLOGICAL FUNCTIONING OF PARENTS WITH CHILDREN RECENTLY DIAGNOSED WITH AUTISM SPECTRUM DISORDERS T. Richard1, K. Savells2, H. Swingle1 * 1University of South Alabama College of Medicine, Mobile, AL and 2University of South Alabama College of Medicine, Mobile, AL*. #### Purpose of Study Autism Spectrum Disorders (ASD) are neurobehavioral phenotypes that affect one in every 150 children. The American Academy of Pediatrics recommends family-centered care for children with special healthcare needs. While studies have shown parents of children with ASD experience more stress than parents of children with other cognitive disabilities, little data are available regarding the psychological function of parents at diagnosis. #### Methods Used Mothers of children newly diagnosed with ASD completed three surveys: the Parenting Stress Index-Short Form (PSI), the Social Capital Scale (SCS), and the Measures of Processes of Care (MPOC-20). The PSI measures parenting stress, the SCS measures a sense of involvement in the community, and the MPOC-20 measures satisfaction with healthcare. The responses of the ASD group were compared to those from parents of children presenting to a general pediatric clinic. Scores from the PSI were also compared to normative data. T-tests were used for data analysis. #### Summary of Results Parenting stress was significantly higher in the ASD group in multiple subscales. The Sense of Belonging subscale from the SCS was lower in the ASD group. No differences in satisfaction were observed between the two groups on the MPOC-20, with most parents being pleased with their children's healthcare. #### Conclusions Parents of children newly diagnosed with ASD are highly stressed on many levels and feel isolated from their community. Healthcare providers should counsel parents on stress management and provide information regarding parent support groups and other community resources at the time of diagnosis. View this table: [Table43](/content/57/1/301/T43) ### 371 FIXING A VERY BAD DAY: THE RETROACTIVE APPLICATION OF STRATEGIES INTENDED TO EXPEDITE PATIENT CARE IN A PEDIATRIC EMERGENCY DEPARTMENT D.J. McLario * 1University of Arkansas for Medical Sciences, Little Rock, AR and 2Arkansas Children's Hospital, Little Rock, AR*. #### Purpose of Study Emergency Department Over-Crowding (EDOC) is prevalent and has been termed a "crisis" by the Institute of Medicine. EDOC is not only inconvenient, but also dangerous, as it compromises timely and effective patient care. Therefore, solutions are urgently needed. Unfortunately, the prospective evaluation of the myriad possible remedies to EDOC is difficult as well as time-consuming and expensive. This study intended to retroactively assess various flow-enhancing strategies in an attempt to identify those likely to provide the greatest benefit. #### Methods Used In order to simultaneously assess the possible effects of a wide variety of possible remedies, we conducted a review of all PED patient medical records (PMR) from a 24 hour period known to have been one of the institution's busiest in recent memory. Each PMR was reviewed to identify "bottlenecks" that delayed patient care. Each PMR was then reconstructed using strategies intended to expedite patient care. #### Summary of Results 194 of 197 possible PED PMR's were available for analysis. Waiting for care consumed 50.78% of PED time (PEDTT). ED "boarding" following admission consumed 5.53% of PEDTT. Time spent in an ED room waiting for Influenza test results while receiving no other care consumed 4.60% of PEDTT. A surge protocol that limited patient waiting times to a presumed 3 hours or less saved 12.19%. A "Point-of-Care" Influenza pathway presuming a 30 minute turnaround time saved 3.02%. The use of Triage Nurse-Initiated-Orders saved 7.16%. Fever-related illnesses comprised 46.39% of PED visits. #### Conclusions The retrospective analysis of PED PMRs facilitates detection of bottlenecks in patient flow as well as the opportunity to retroactively assess various possible solutions simultaneously. In our 24 hour model, the "implementation" of 3 non-overlapping interventions reduced PEDTT by 22.37%, thereby identifying significant potential for increased functional capacity. In addition, considerable PED time was devoted to patient evaluations for fever-related complaints, suggesting educational efforts directed toward appropriate caregiver response to fever may reduce PED use as well. ### 372 CALCULATING POSITIVE PREDICTIVE VALUES OF SCREENING ALERTS FOR LOOK-ALIKE, SOUND-ALIKE DRUG SUBSTITUTIONS IN PEDIATRIC PRESCRIPTIONS WITH AND WITHOUT DIAGNOSTIC DATA W.T. Basco, M. Ebeling, T.C. Hulsey, K. Simpson *Medical University of South Carolina, Charleston, SC* #### Purpose of Study To evaluate how the Positive Predictive Value (PPV) of screening alerts for Look-Alike, Sound-Alike (LASA) substitution errors differ when administrative database diagnoses are added to pharmacy administrative data. #### Methods Used Retrospective review of 2000-2006 Medicaid paid pharmacy claims from one state. From a list of known LASA drug pairs, we identified the following test list of 11 LASA drug pairs: Adderall/Inderal; Allegra/Viagra; Colace/Cozaar; Folic Acid/Folinic Acid; Keppra/Kaletra; Lamictal/Lamisil; Metadate/Methadone; Miralax/Mirapex; Prilosec/Prozac; Tegretol/Tequin; and Topamax/Toprol XL. Patients who received one of the drugs in a pair at least 3 times in 12 months were considered to be appropriately prescribed that drug (a "usual drug"). Patients who then received the first dispensing of the paired drug within 6 months of the usual drug triggered a "screening alert." We calculated the PPV of the screening alerts by a pharmacy history definition ("true error" = received only ONE dispensing of the paired drug) and by a pharmacy + diagnosis definition ("true error" = received only ONE dispensing of the paired drug and had no diagnoses supporting use of the paired drug). #### Summary of Results There were over 700,000 Medicaid recipients and >16 million prescriptions in the dataset. Up to 3% of the patients routinely prescribed one drug of a LASA pair received the paired drug. Among the 9 drug pairs that generated screening alerts, the PPV of those alerts with pharmacy data only ranged from 75% (for Tegretol/Tequin) to "0″ (for Folic Acid/Folinic Acid and Keppra/Kaletra). Addition of the diagnostic data did not change PPV for 2 pairs: Colace/Cozaar and Topamax/Toprol XL. The PPV of screening alerts generally decreased for other pairs, but the PPV remained >10% except for Tegretol/Tequin, where all of the patients on Tegretol who triggered a screening alert for filling Tequin had a supporting diagnosis in the administrative data. #### Conclusions The positive predictive value of a screening alerts remained ≥10% for 6 of 9 LASA pairs generating alerts after review of diagnoses. These data suggest that pharmacists should screen any person routinely on one drug in a LASA pair who then presents with the first request to fill the paired drug. ### 373 EMERGENCY DEPARTMENT OVERCROWDING PROLONGS TIME TO ANTIBIOTICS IN FEBRILE NEONATES S. Shirm, S. Bowman, D. McLario, J. Graham *U of Arkansas College of Medicine, Little Rock, AR* #### Purpose of Study Emergency department (ED) overcrowding (EDOC) is an increasingly common problem and has been called a "crisis" by the Institute of Medicine. EDOC results in lower patient and staff satisfaction, but there is also recent evidence that EDOC may increase morbidity and mortality for certain time sensitive emergency conditions. The purpose of this study was to examine whether EDOC is associated with increased time to antibiotic administration for febrile neonates presenting to the ED. #### Methods Used The ED of Arkansas Children's Hospital installed a computerized tracking board system in October, 2007. We searched the hospital information system to identify all patients aged 30 days and under who had either a dose of ampicillin or a charge for a lumbar puncture tray. Febrile neonates who presented to the ED between October, 2007 and May, 2008 were included. The computer tracking system was queried to determine the number and acuity of patients in the ED when each febrile neonate presented. The emergency department chart was reviewed for additional information. #### Summary of Results There were 108 neonates who presented to the ED with fever during the study period. Neonates presenting to the ED when the ED was 20% over capacity had longer time from arrival until antibiotics were administered (255 vs.218 minutes, *P* < 0.02). When the ED was at 50% overcapacity, the neonates had an even longer time to antibiotics (265 vs. 225 min, *P* = 0.038). There was no difference in hospital length of stay between those who presented during EDOC and those who presented when there was not EDOC. Hospital charges were higher in the 20% EDOC group, but the difference was not statistically significant ($8908 vs. 24,966). #### Conclusions Emergency department overcrowding is associated with increased time for febrile neonates to have their possible sepsis evaluation and have antibiotics administered. EDOC is not only a satisfaction issue, but may also affect patient safety. ### 374 TARGETING ATTENDANCE AT AN URBAN CHRONIC KIDNEY DISEASE CLINIC SERVING MINORITY POPULATIONS: A QUALITY ASSURANCE PROGRAM S. Sadhu1,2, J. Esquenazi2, O. Lenz1 * 1University of Miami Miller School of Medicine, Miami, FL and 2Jackson Memorial Hospital, Miami, FL*. #### Purpose of Study We have previously shown that non-adherence to scheduled clinic appointments is an important predictor of poor outcomes in our chronic kidney disease (CKD) clinic serving mainly an inner city minority population. The no-show rate remained high despite using mailed appointment reminders. Consequently, we initiated a Plan-Do-Check-Act (PDCA) cycle to address this problem as part of a quality assurance program. #### Methods Used We telephoned all patients scheduled for the CKD clinic within one week of their appointment. Two separate attempts were made to reach patients who could not be reached the first time. A voicemail message was left for those who could not be directly contacted. #### Summary of Results 199 patients were called over a three-week-period. 71% of patients were reached either directly or via voicemail message while 29% could not be contacted. The majority of the latter (77%) had had their phone disconnected or the telephone number on file was wrong. The average no-show rate decreased from 29 ± 7% to 25 ± 4% after the added telephone reminder (*P* > 0.05). 83% of the patients that were reached in person or by voicemail kept the appointment, but only 57% of those that we could not reach attended the clinic (*P* = 0.0002, odds ratio 3.7 [1.9-7.3]). In addition, patients that were reached were more likely to re-schedule their appointment rather than just missing it. #### Conclusions A large clinic population could not be reached by telephone, and these patients were more likely to miss appointments. Overcoming this communication barrier may lead to improved adherence to scheduled clinic visits, resulting in better outcomes of CKD care for inner city minority populations. Our future improvement efforts will therefore target the difficult to reach population, restarting the PDCA cycle. ## **Hematology and Oncology II Concurrent Session** 1:00 PM Saturday, February 14, 2009 ### 375 CORRELATION OF SONOGRAPHIC FINDINGS WITH HISTOPATHOLOGY OF SUSPECTED TESTICULAR LESIONS IN ACUTE LEUKEMIA A. Qudeimat1, F. Wilson1, H. Imran1, S. Figarola2, J. Polski3, A. Rao1 * 1University of South Alabama, Mobile, AL; 2University of South Alabama, Mobile, AL and 3University of South Alabama, Mobile, AL* #### Purpose of Study Testicular infiltration is seen in up to 8% of children with leukemia. Sonographic evaluation is often the first diagnostic procedure performed in such patients who present with a painless testicular enlargement. We present 3 cases in which ultrasound(US)showed findings suspicious for acute leukemic infiltration;subsequent biopsies in all cases showed no involvement #### Methods Used Case 1: Ten year old Caucasian male with history of acute lymphocytic leukemia(ALL)found to have a discrepancy between the size of both testicles(left larger)at 1 year post therapy follow-up. Testicular US showed left testicular enlargement with abnormal hypoechoic focus in the inferior aspect of the testicle consistent with a focal leukemic infiltrate. Right testicle also showed abnormal echo shadows. Case 2: Thirteen year old Caucasian male with refractory acute myeloid leukemia presented with painful testicular enlargement 2 months after initiation of treatment. US showed small testicles with bilateral hypoechoic masses suspicious of leukemic infiltrates. Case 3: Four year old Caucasian male with history of Philadelphia chromosome positive ALL found to have a left testicular enlargement on physical examination at diagnosis. Subsequent US revealed a hypoechoic mass within the left testicle consistent with a leukemic focus. #### Summary of Results Case 1: Bilateral biopsies only showed atrophy of the right testis consistent with chemotherapy effect. Case 2: Biopsy did not show involvement by acute leukemia. Case 3: Biopsy was consistent with normal testicular tissue. #### Conclusions We found discrepancy between testicular sonographic findings and tissue biopsy results in diagnosing leukemic testicular infiltration. Some investigators report a high sensitivity and specificity of testicular US for the diagnosis of testicular malignancy, others have found a low positive predictive value. US is preferred due to its noninvasive nature and cost effectiveness. Further studies are needed to clarify the role and value of performing testicular US in the diagnosis of suspicious lesions in acute leukemia. More sensitive and specific tools may be needed to help determine the need for biopsy. Clinical suspicion still remains the best determinant for biopsy. ### 376 POLYCYTHEMIA, LEUKOCYTOSIS AND T-LYMPHOBLASTIC LYMPHOMA ASSOCIATED WITH A 46 XY T(8;13)(P12;Q12) KARYOTYPE S. Yellapragada1, M. Mims1, M. Lewis3, C. Jackson2, M. Udden1 * 1Baylor College of medicine, Houston, TX; 2Baylor College of Medicine, Houston, TX and 3Baylor College of Medicine, Houston, TX* #### Case Report An unusual myeloproliferative syndrome (8p11 syndrome) is linked to the translocation t(8,13)(p11-p12;q11-12).This results in fusion between the FGR1 gene on chromosome 8 and zinc finger protein 198(ZNF198)on chromosome 13.The fusion tyrosine kinase is associated with myeloproliferative disorder(MPD) with leukocytosis, eosinophilia and progression to T-Cell lymphomas and AML. We describe a 50 year old Nigerian man who presented with polycythemia (Hb 22 gm/dL), leukocytosis (WBC 21,000 with 86% neutrophils and 9% eosinophils) and diffuse lymphadenopathy. His erythropoietin was low and JAK2 V617F mutation and RT PCR for BCR-ABL were negative. Lymph node biopsy revealed T-Cell lymphoblastic lymphoma expressing CD3, CD30, CD1a and TDT. Bone marrow aspirate was hyper-cellular with 3% blasts with 46XY t(8,13)(p12;q12) karyotype in 18/20 cells. Serologies for HIV, EBV, HTLV1, Hepatitis were negative. Association of the 8p11 syndrome with his T-Cell ALL was confirmed by identifying the FGR1-ZNF198 fusion transcript by RT-PCR in the lymph node block. Treatment consisted of phlebotomy and chemotherapy with HCVAD-MTX/ AraC regimen with complete resolution of lymphadenopathy but the marrow remained hypercellular with presence of t(8;13)(p12;q12)in 12/20 cells. While on HCVAD his T-Cell lymphoblastic lymphoma relapsed with no response to salvage therapy with Nelarabine. He developed profound thrombocytopenia, leukocytosis, pleural effusion with lymphoblasts and died of respiratory failure. Our patient had translocation 8p12-12 resulting in a FGR1/ZNF198 fusion product with a striking combination of polycythemia, leukocytosis and lymphadenopathy. The latter was T-Cell lymphoblastic lymphoma which has been reported with this syndrome. Subsequent course showed discordant response of his MPD (resistant) and T-Cell lymphoblastic lymphoma (initially responsive) emphasizing the need for treatment of the underlying MPD. The kinase inhibitor Midostaurine is active in preclinical models and treatment of a patient with FGR1/ZNF198 related MPD. Bone marrow transplantation has been undertaken in others. Our patient's rapid deterioration prevented use of either treatment. ### 377 BCR-ABL FUSION GENE INVOLVING MAJOR BREAKPOINT CLUSTER REGION IN A CHILD WITH ACUTE LYMPHOBLASTIC LEUKEMIA V. Narayanaswamy1, M.A. Vasef2, A. Rao1 * 1University of South Alabama, Mobile, AL and 2University of New Mexico, Albuquerque, NM* #### Case Report Introduction: The presence of Philadelphia chromosome (Ph1) is rare in childhood ALL and is associated with the worst outcome. The predominant breakpoint type in pediatric Ph1 chromosome-positive ALL is a break involving the minor breakpoint cluster region (m-bcr).We present a case of Ph1 positive ALL with a break in the major breakpoint cluster region (M-bcr) seen predominantly in CML, and the child's response to chemotherapy. #### Case report 4 year male presented with a 2 week history of pallor, bruising, weight loss and decreased appetite. Physical examination revealed pallor, splenomegaly, ecchymoses and enlarged testicles. Hemoglobin was 6.2g/dl, WBC 7,200/mm3, platelets 21,000/mm3, LDH 903 U/L.The peripheral blood smear, bone marrow and CSF showed numerous blasts and flow cytometry confirmed precursor B-cell ALL. Testicular biopsy was negative for leukemia. Cytogenetics revealed t(9;22)(q34;q11).Quantitative PCR on the bone marrow aspirate showed a BCR-ABL/ABL ratio of 1.6 consistent with high levels of bcr-abl transcripts. Peripheral blood smear did not reveal morphologic features of CML presenting with blast crisis. The patient was classified as high risk and was started on 4 drug induction. At the end of induction bone marrow showed morphologic remission and PCR showed a log reduction in the Philadelphia chromosome level (BCR-ABL/ABL ratio of 0.012). Imatinib mesylate was added to therapy in consolidation as per the very high risk protocol. Imatinib dose modification was needed following gastrointestinal toxicity. He continued to show log reduction in BCR-ABL /ABL ratio to 0.00022 after consolidation and is currently in morphologic remission with negative cytogenetic markers. #### Conclusion The development of imatinib mesylate has opened novel therapeutic opportunities for the management of Ph1-positive ALL. We present this case due to the rarity of M-bcr translocation in pediatric ALL and the response to imatinib in spite of dose reduction secondary to toxicity. Serial analysis of BCR-ABL mRNA levels by quantitative PCR during and after completion of therapy accurately reflects the level of disease suppression and is an effective method for monitoring residual disease and treatment efficacy. ### 378 CASE REPORT OF MYCOSIS FUNGOIDES EVOLVING INTO AN AGGRESSIVE CUTANEOUS T-CELL LYMPHOMA J.B. Gatewood1, C. Bigelow1, J. Lam2 * 1University of MS Medical Center, Jackson, MS and 2University of MS Medical Center, Jackson, MS* #### Case Report Benjamin Gatewood, MD; Carolyn Bigelow, MD; John Lam, MD University of Mississippi Medical Center, Jackson, MS #### Abstract Mycosis fungoides is an uncommon malignancy that composes one of the indolent classes of non-Hodgkin's lymphoma and is characterized by malignant T-cell aggregation in the cutaneous tissues of the body. The cutaneous manifestations at presentation are extremely variable and the treatment options vary based on the degree of skin, lymph node, and visceral organ involvement. The exact etiology of mycosis fungoides is unknown, however, it is known that often the malignant cells are that of a T-cell lineage. There is also ongoing investigation into mycosis fungoides proclivity for cutaneous tissues and current thoughts include over-expression of intracellular adhesion molecules by the cutaneous tissue and of lymphocyte function-associated antigen by the malignant cells. We present a patient initially diagnosed with mycosis fungoides that later underwent a dramatic transformation. Upon his initial presentation in March, 2007, he had small lesions appearing to be psoriasis but with pathology consistent with mycosis fungoides on skin biopsy. However, the patient failed to keep his follow-up appointments and presented more than a year later with extensive skin involvement. A repeat biopsy was completed that revealed that the patient's initial indolent mycosis fungoides had now transformed into an aggressive peripheral T-cell lymphoma. He subsequently was treated with systemic combined chemotherapy with a modest improvement in his lymphoma. Transformation of mycosis fungoides into a more aggressive T-cell lymphoma has been studied in the past and fewer than 50% of patients with this rare disease actually evolved into a more aggressive variant. Our patient's transformation is documented with progressive skin biopsies that reveal that his initial indolent mycosis fungoides transformed into a large cell variant of a cutaneous T-cell lymphoma over the course of approximately one year, a very short period of time for this type of transformation to occur. During this same time period, the patient also had a dramatic increase in his cutaneous involvement revealing the extremely aggressive nature of his neoplasm. ### 379 A CASE REPORT OF PULMONARY PAPILLOMATOSIS WITH PROGRESSION TO MULTIFOCAL SQUAMOUS CELL CANCER OF THE LUNG B.E. Persing, J.C. Williams, S.L. Elkins, V.E. Herrin *Univ. of Mississippi Medical Center, Jackson, MS* #### Case Report **Introduction**: Recurrent respiratory papillomatosis (RRP) is the result of exposure to Human Papilloma Virus (HPV) that occurs during delivery. Development of RRP is a result of HPV infection that involves the larynx and trachea. Patients with laryngo/tracheal involvement of HPV will progress to RRP in five percent of cases. Of those that progress to RRP only one percent will develop invasive squamous cell cancer of the lung. This tends to effect younger patients and is, thus, even more devastating. #### Case Presentation We present the case of a 32-year old non-smoking white female who presented with a long history of laryngeal and tracheal papillomatosis. She had numerous interventions including laser ablation of lesions, tracheostomy, and myomectomies. On computed tomography (CT) scan of the neck she was incidentally found to have a lung lesion that was assumed to be papillomatosis. On subsequent CT imaging one area increased in size rapidly and was noted to have a necrotic center. She was taken to surgery, and the mass was removed along with two other viscera pleural-based masses, all of which revealed invasive well differentiated squamous cell carcinoma. #### Conclusion While RRP is uncommon and conversion of papillomas to overt lung malignancy is even less common, the results can be devastating. Little more that intermittent case reports, some at the time of autopsy, guide clinical treatment. Oral tyrosine kinase inhibitors such as gefitinib and erlotinib show some promise in these lesions. Treating the underlying HPV infection may also be beneficial in some cases. With the advent of HPV vaccination this may become even less common than it is at the present time. ### 380 SUCCESSFUL TREATMENT OF HYPEREOSINOPHILIC SYNDROME WITH CYCLOSPORINE C. Donald, M. Kahn *Tulane University, New Orleans, LA* #### Case Report A 63 year old man with lymphocytic variant hypereosinophilic syndrome (HES) characterized by a T-cell receptor gene rearrangement was treated with cyclosporine with marked improvement in his symptoms and reduction in his total eosinophil count. We present this case to demonstrate cyclosporine as an effective treatment of this rare entity. ### 381 MACROPHAGE ACTIVATION SYNDROME IN A CHILD WITH EHRLICHIA CHAFFEENSIS INFECTION S. Burns, R. Saylors, M. Amir *University of Arkansas for Medical Sciences, Little Rock, AR* #### Case Report Purpose of Study: We present a patient with hemophagocytosis as a result of macrophage activation syndrome secondary to Ehrlichia chaffeensis infection. The purpose is to enhance the clinician's prompt recognition and treatment in order to reduce mortality associated with this condition. #### Methods To report a patient with disseminated ehrlichiosis in whom early recognition and aggressive treatment resulted in complete recovery #### Summary A 10 year old male presented to Arkansas Children's Hospital with a 5 day history of fever, mild upper respiratory tract infection, emesis, loose stools, decreased activity and increased bruising. At initial presentation he had a generalized seizure, hypotension, lethargy, and significant hepato-splenomegaly. Laboratory studies showed pancytopenia, disseminated intravascular coagulopathy (DIC), hypofibrinogenemia, hypertriglyceridemia, elevated serum ferritin, elevated liver enzymes, and elevated LDH. Imaging studies showed pleural effusions, generalized prominence of diffuse lymphadenopathy, and ascites without evidence of intracranial bleeding or mass lesion. He underwent an extensive infectious disease work-up. Bone marrow examination showed hemophagacytosis without evidence of malignancy by flow cytometry. He fulfilled all of the criteria for the diagnosis of hemophagocytic lymphohistiocytosis (HLH) and was started on appropriate chemotherapy. Two days later the Ehrlichia chaffeensis PCR was reported to be positive. Doxycycline was started and the chemotherapy was discontinued. He quickly defervesced with significant improvement in his clinical condition with doxycycline treatment. Repeat bone marrow examination showed normal morphology with complete resolution of the hemophagacytosis. Genetic testing was negative for the perforin 1, MUNC 13-4, and SYNTAXIN 11 gene abnormalities that have been associated with HLH. Follow-up NK functional studies were normal on repeat testing approximately 3 months after hospital discharge. #### Conclusion This case illustrates the importance of considering all etiologies for hemophagocytic lymphohistiocytosis. While the patient denied tick exposure, it is important to obtain a thorough history and consider all infectious causes of secondary HLH, particularly in areas where these organisms are endemic. ### 382 PSEUDOTHROMBOCYTOPENIA AND PLATELET DYSFUCNTION: A DIAGNOSTIC DILEMMA K.W. Boyd, S. Elkins, J. Files *University of Mississippi Medical Center, Jackson, MS* #### Purpose of Study To present a case of pseudothrombocytopenia with associated platelet dysfunction. #### Methods Used A 47-year-old white female presented with complaints of easy bruising and metromenorrhagia. She was noted to have numerous ecchymoses and scattered petechiae. Her platelet count was 2,000/cmm and her peripheral smear showed multiple large platelet aggregates. Her platelet count was re-checked using citrate and heparin tubes, which also resulted in platelet clumping. Bone marrow examination was normal. A warmed finger stick sample revealed a platelet count of 166,000/cmm. Cold agglutins were negative, but given the improved count with the warmed sample the patient was felt to have cold-related platelet aggregation. At her one-year follow-up appointment, she complained of a persistent bleeding diathesis that was made worse in cold weather and was referred to our institution for further evaluation. #### Summary of Results Review of her peripheral smear and repeat bone marrow exam confirmed the reported findings from the outside hospital. Her blood was collected in multiple reagents and warmed, all of which resulted in large platelet aggregates. Manual platelet count, electron microscopy and aggregation studies were all attempted without success secondary to the large platelet clumps. Bleeding time was prolonged. Repeat cold agglutins were negative, but quantitative IgM was elevated in a polyclonal pattern. The patient was continued on no therapy. At her most recent follow-up appointment the patient noted less bruising. Her smear revealed smaller platelet clumps and the automated platelet count was 82,000/cmm. Aggregation studies at this time were negative. #### Conclusions Pseudothrombocytopenia is an artifact of electronic blood-counting machines that can cause erroneous low platelet counts due to their in vitro clumping. Platelet agglutination in response to EDTA is well recognized and produces pseudothrombocytopenia in up to 0.1% of blood samples. In contrast, EDTA- independent platelet agglutination is a much less frequent phenomenon and only a few cases have been described. To our knowledge there have not been any reported cases of platelet dysfunction in association with pseudothrombocytopenia. ### 383 AN UNUSUAL CASE OF HEMATOCHEZIA IN A PREVIOUSLY ASYMPTOMATIC 23-YEAR-OLD MALE R.G. Argula1, T.E. Dantzler2 * 1Medical University of South Carolina, Charleston, SC and 2Medical University of South Carolina, Charleston, SC* #### Case Report A 23-year-old Pakistani male with no known past medical history, presented to the ER from a primary care clinic, where he initially presented with complaints of new onset nausea, vomiting, nosebleeds, and bright red blood in the stool. He was hypotensive with a blood pressure of 93/60 mm Hg. Physical exam showed a thin appearing, diaphoretic male with an abdominal exam that was remarkable only for a palpable splenic tip. Initial lab work was notable for low hemoglobin (5.8g/dl) and a platelet count of 94,000/cubic mm. An emergent EGD performed in the ICU revealed grade 3 non-bleeding esophageal varices and a large blood clot in the gastric fundus. A colonoscopy performed later revealed rectal varices. Imaging of the abdomen (US, CT and MRA) revealed massive splenomegaly, a portal vein thrombus with cavernous transformation of the distal portal vein and a massive spleen (25cm). The imaging also showed multiple collaterals in the upper abdomen and prominent esophageal and gastric varices. A liver biopsy and porto-systemic pressure gradient were normal. A search for a thrombophilic condition revealed that this patient was homozygous for the 4G allele in the PAI-1(plasminogen activator inhibitor) promoter region. Individuals who are homozygous for the 4G allele in the promoter region of the gene for PAI-1 have higher levels of circulating PAI -1, when compared to normal individuals and individuals with other polymorphisms in this region. PAI -1 is a major inhibitor of fibrinolysis and researchers have reported numerous associations between high PAI-1 levels and the occurrence of venous thromboses. There is limited evidence to support the use of anti-coagulants in a patient with chronic portal vein thrombosis with a cavernous transformation already decompressing the portal vein. Anticoagulation is especially important in patients with an underlying thrombophilia in whom the recurrence of thrombosis with a risk of variceal bleeding is high. This case report highlights: 1)the importance of a thorough evaluation of underlying thrombophilia in a cavernous portal vein thrombus, 2) the first reported instance of a portal vein thrombosis associated with the 4G polymorphism in an adult. ### 384 REFRACTORY AIHA, BONE MARROW ERYTHROID HYPERPLASIA AND RETICULOCYTOPENIA WORKUP AND THERAPY: CASE REPORT AND REVIEW OF LITERATURE R. Fahed *TULANE UNIVERSITY, New Orleans, LA* #### Case Report 48 YO Caucasian male, diagnosed with haemolytic anemia post levaquin therapy for urinary tract infection. Workup was consistent with warm antibody AIHA, started prednisone, patient shortly after diagnosis became reticulocytopenic. Underwent reticulocytopenia workup including bone marrow biopsy, patient was considered steroid refractory after 6 weeks of therapeutic dose and underwent splenectomy. Patient continued to be RBC transfusion dependent, with massive hemolysis and reticulocytopenia. Rituximab was given with remarkable delayed response. We are presenting a case of a severe refractory AIHA, bone marrow erythroid hyperplasia, and paradoxical reticulocytopenia including all the extensive secondary workup for refractory haemolytic anemia and reticulocytopenia. Review of available literature, and the role of reticulocytopenia as a predictor of poor outcome and steroid refractoriness. ### 385 CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME Z. Sharif1, H. Alshayeb1, D. Hansen1, B. Abbasi1, S. Zaidi1, F. Abu Alrub1, W. Nasser2, S. Haider1 * 1UTMEM, Memphis, TN and 2UTMEM, Memphis, TN* #### Case Report Catastrophic Antiphospholipid Syndrome is a rare form of Antiphospholipid Syndrome (APS) involving less than 1% of APS patients. Generally of acute onset it is defined by involvement of at least three different organ systems over a period of days to weeks and histological evidence of small vessel occlusion in at least one organ. Thrombocytopenia is common. Mortality rate is up to 50% despite treatment with anticoagulation, immunosuppession and plasma exchanges. Extensive cytokine release is a proposed pathologic mechanism. About half of the cases have identifiable infection, trauma, medication, or surgery as a trigger. We present a case report of a patient with CAPS associated with marantic endocarditis, complicated by heparin induced thrombocytopenia (HIT). A 48 y/o healthy female presented with acute left hemiparesis and left lower extremity (LE) deep venous thrombosis (DVT). MRI/MRA of brain showed multiple right hemispheric embolic infarcts. Echocardiogram showed aortic valve vegetations. Infective endocarditis work up was negative. Despite anticoagulation with heparin, the left LE DVT progressed, developing into phlegmasia cerulea dolens and gangrene necessitating an amputation. Pathology showed thrombosis of femoral and tibial vessels. Diagnostic workup revealed prolonged aPTT, PT and INR, not corrected by mixing studies. Anti cardiolipin antibodies and lupus anticoagulant were positive. Evaluation for homocysteine, proteins C and S, factor V Leiden and prothrombin mutations, factor VIII and antithromin III levels was unremarkable. Serologies for RF, ANA, Anti DNA, Anti RNP, Anti-sm, C-ANCA and P-ANCA were negative. Patient was diagnosed with Primary APS. Thrombocytopenia on Day 5 of heparinization and development of acute DVT in right upper extremity prompted management of HIT which was confirmed by serotonin release assay. Despite anticaogulation by various agents including argotroban, fondaparinux and lepirudin; immunosuppressive therapy by prednisone and Rituximab; and initiation of plasma exchanges, patient went on to develop progressive thrombo-embolism including pulmonary, renal and splenic infacrtion and right LE DVT. Course was complicated by acute upper GI bleed, respiratory failure ultimately culminating in fatal cardiopulmonary arrest. ## **Infectious Diseases II Concurrent Session** 1:00 PM Saturday, February 14, 2009 ### 386 INTERFERON-GAMMA ENHANCES THE LIN-CKIT + SCA-1 +CELL RESPONSE TO ESCHERICHIA COLI BACTEREMIA A.D. Weinberg1, R.W. Siggins2, G.J. Bagby2,1, S. Nelson1,2, P. Zhang1,2 * 1LSUHSC, New Orleans, LA and 2LSUHSC, New Orleans, LA* #### Purpose of Study Interferon-γ (IFN-γ) is a pro-inflammatory cytokine that plays an important role in host defense against infections. Our previous studies have shown that in response to systemic bacterial infection, the number of bone marrow lin-ckit + Sca-1 + cells is significantly increased. This expansion of marrow lin-ckit + Sca-1 + cell population is an important component of the granulopoietic response to bacterial infection. Our current study investigated the effect of IFN-γ on the lin-ckit + Sca-1 + cell response to E. coli bacteremia. #### Methods Used Recombinant murine IFN-γ (10∧5 U in 100 µl of saline/mouse) or an equal amount of saline was administered to male C57BL/6 mice by intravenous injection. The animals were sacrificed 24 h and 48 h later. In a subset of animals, intravenous challenge with E. coli (∼10∧7 CFUs /mouse) in conjunction with 5-bromo-2-deoxyuridine (BrdU, 1 mg in 100 μl of PBS) was given to mice 12 h after administration of IFN-γ. The animals were sacrificed 24 h thereafter. Hematopoietic precursor cells and granulocytes in the bone marrow and blood samples were analyzed by flow cytometry. #### Summary of Results Intravenous administration of IFN-γ significantly increased the number of lin-ckit + Sca-1 + cells in the bone marrow at 24 h, which was associated with a reduction of marrow lin-ckit + Sca-1- cells. The number of lin-ckit + Sca-1 + cells in the peripheral blood was also increased at both 24 h and 48 h after administration of IFN-γ. IFN-γ caused an increase in BrdU incorporation into marrow lin-ckit + Sca-1 + cells in vivo and induced Sca-1 expression by marrow lin-ckit + Sca-1- cells in vitro. Administration of IFN-γ 12 h prior to initiation of E. coli bacteremia significantly enhanced the marrow lin-ckit + Sca-1 + cell response at 24 h post E. coli bacteremia. IFN-γ pretreatment also enhanced bone marrow release of newly produced granulocytes into the systemic circulation following E. coli bacteremia. #### Conclusions These results demonstrate that IFN-γ enhances the expansion of bone marrow lin-ckit + Sca-1 + cell population and the granulopoietic response during E. coli bacteremia, which may serve as a mechanism underlying the beneficial effects of IFN-γ on host defense against bacterial infection. ### 387 DAPTOMYCIN THERAPY IS ASSOCIATED WITH LESS DERMONECROSIS COMPARED WITH VANCOMYCIN THERAPY IN A MURINE SOFT TISSUE INFECTION MODEL CAUSED BY COMMUNITY-ASSOCIATED ISOLATES OF STAPHYLOCOCCUS AUREUS (CA-MRSA) R. Kudumula1,3,2, A. Rye1,3, A.J. Talati1,3,2, E.A. Meals3, B.K. English1,3 * 1UTHSC, Memphis, TN; 2UTHSC, Memphis, TN and 3Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, TN* #### Purpose of Study We have previously reported that exposure of clinical isolates of CA-MRSA to daptomycin (DAP) compared with vancomycin (VAN) results in a reduced macrophage production of tumor necrosis factor (TNF) and nitric oxide (NO). We hypothesized that daptomycin therapy of experimental murine soft tissue infections caused by CA-MRSA strains would be associated with a blunted host inflammatory response and result in less severe soft tissue lesions and less dermonecrosis. #### Methods Used We injected groups of 10 SKH1 hairless (immunocompetent) mice from Charles River in the right upper thigh muscle with 5 × 107 - 1 x109 cfu of three different clinical isolates of CA-MRSA. Two USA300 isolates were employed: 6U24, a previously-studied clinical isolate from a pediatric patient in Memphis with osteomyelitis and bacteremia; and LAC, a well-characterized California isolate. One USA 400 isolate - the well-characterized Minnesota strain, MW2 was used. After inoculation, we initiated antibiotic treatment (either DAP or VAN) at 18 hours after bacterial inoculation. In the first set of experiments all the mice were observed for ten days. The lesion size and character were recorded and sacrificed. In the second set of experiments, we sacrificed the mice as the lesions appeared. #### Summary of Results Mice injected with the higher inoculum (109 cfu) of either of the two isolates 6U24 or LAC - but not the MW2 isolate - consistently developed large soft tissue lesions with dermonecrosis. Lesions in the mice treated with DAP compared with VAN developed markedly less dermonecrosis and were approximately 20% smaller in size after 10 days, in the first set of experiments. In the second set of experiments the mice treated with VAN developed lesions at 72 hrs while DAP treated mice, developed lesions at 96 hrs. #### Conclusions We found that in this mouse model, DAP is more effective than VAN in treating severe soft tissue infections caused by USA300 strains of CA-MRSA. ### 388 ROLE OF DELTA TOXIN IN THE MACROPHAGE RESPONSE TO STRAINS OF COMMUNITY-ASSOCIATED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (CA-MRSA) EXPOSED TO EITHER VANCOMYCIN OR DAPTOMYCIN C. Acuna1,2, T. Spentzas1,2, E. Meals1, R. Kudumula1,2, B. Johnson1, B. English1,2 * 1University of Tennessee Health Science Center, Memphis, TN and 2Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, TN* #### Purpose of Study We previously reported that macrophages exposed to either of two Memphis USA300 CA-MRSA isolates in the presence of daptomycin (DAP) compared with vancomycin (VAN) secreted less tumor necrosis factor (TNF). We hypothesized that this difference resulted from reduced release of bacterial toxins implicated in CA-MRSA pathogenesis after exposure to DAP (vs. VAN). To determine whether Delta Toxin and/or phenol soluble modulins (PSMs) play important roles in triggering the macrophage inflammatory response to USA300 and/or USA400 CA-MRSA strains exposed to VAN or DAP. #### Methods Used RAW 264.7 murine macrophages were stimulated for 18 hrs with 106 cfu/mL of CA-MRSA isolates in the presence of VAN 20 mcg/L or DAP 20 mg/L. We tested parental MRSA strains LAC (USA300 lineage) and MW2 (USA400 lineage) and isogenic strains engineered to lack expression of Delta Toxin (hld) or one of the PSMs (αor β) in each parental strain (gifts of Michael Otto, Ph.D.). After stimulation, supernatants were collected and assayed for TNF concentration by ELISA. #### Summary of Results We found that TNF secretion by macrophages exposed to any of the eight CA-MRSA strains tested was consistently lower in the presence of DAP compared with VAN (F(3, 35) = 73.92 *P* < 0.05) and the magnitude of the difference was comparable for each of the isogenic isolates. Deletion of delta toxin led to lower TNF secretion by macrophages exposed to the bacteria in the presence of DAP (significant reductions in both LAC and MW2 backgrounds) or VAN (significant reduction in MW2 background; trend in LAC background). #### Conclusions Our data indicate that (1) Delta Toxin plays an important role in triggering macrophage TNF secretion by both LAC and MW2 strains of CA-MRSA, (2) Exposure of either of the two CA-MRSA isolates (or any of the isogenic deletion mutants) to DAP (vs. VAN) results in reduced macrophage TNF secretion, and (3) Differential release of delta toxin or PSMs is unlikely to explain the reduced macrophage TNF response to MRSA isolates exposed to DAP (vs. VAN). ### 389 A MODEL FOR THE CONTROL OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS COLONIZATION AND INFECTION IN AN INTENSIVE CARE UNIT J.H. Etienne1, J. Figueroa1, E. Bourque2, C. Scioneaux2, * 1Louisiana State University Health Sciences Center, New Orleans, LA and 2Touro Infirmary, New Orleans, LA* #### Purpose of Study High rates of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection among our intensive care unit (ICU) patients have been difficult and at best partially successful to control in spite of targeted isolation. We are reporting the effect of establishing an Infection control bundle on the rate of MRSA colonization and infection in a Community hospital ICU. #### Methods Used From 2001 to 2003, the incidence rate of MRSA colonization and infection was ranging from 2.5 per 1,000 patient-days to a peak of 3.71 by early 2004. In order to curb this increase and the subsequent associated mortality and morbidity, the infection control department aggressively instituted a bundle of precautionary measures that comprised (1) constant education, (2) audits, (3) isolation of known case with dedicated equipment, (4) hand hygiene, (5) preemptive use of gloves (5) preemptive use of gown if there is a known case of multi-drug resistant organism (MDRO), (6) decolonization. The data from the ICU 3 years post-implementation are reviewed to monitor the effect of the bundle. #### Summary of Results With implementation and active diffusion of the new guidelines, the response was immediate. In 2005, a nadir of 1.06/1,000 patient-years was achieved. By 2007, however, the incidence rate of MRSA colonization and infection has plateaued at 1.56/1,000 patient-years. All in all, the incidence of MRSA in the ICU has been at one of its lowest level since the introduction of the program. 36 months after the outbreak, this model continues to be accepted and practiced successfully by the ICU staff. #### Conclusions MRSA control programs can be effective in controlling an outbreak and maintaining a low incidence of nososcomial MRSA colonization and infection in the ICU population. Our study as many others is adding more evidence that a multipronged strategy may be necessary to control the rate of MRSA infection and colonization ### 390 CYSTIC FIBROSIS COLONIZATION WITH THE UNUSUAL PLANT PATHOGEN, RHIZOBIUM RADIOBACTER D. McCastlain1, K. Muldrew2, T. Beavers-May3, H. Maples2 * 1UAMS College of Pharmacy, Little Rock, AR; 2UAMS College of Pharmacy, Little Rock, AR and 3Arkansas Children's Hospital, Little Rock, AR* #### Purpose of Study This study is intended to provide the first detailed description of patients with cystic fibrosis (CF) and concomitant Rhizobium radiobacter sputum colonization, outlining their clinical course and examining the antibiotic susceptibility of this organism. #### Methods Used A retrospective chart review was conducted on four CF patients with a history of R. radiobacter growth. Previous organisms, antimicrobial history, and pulmonary function tests were collated. Available bacterial isolates collected at the time of colonization where subjected to rDNA gene analysis. Frozen samples were sub-cultured onto blood agar and MacConkey agar plates to ensure viability and purity. Biochemical tests and E-test susceptibility were performed. #### Summary of Results Two CF patients grew R. radiobacter initially during an acute pulmonary exacerbation, while the other two patients were clinically stable at the time of isolation. Two available samples were positively identified as R. radiobacter using 16S rDNA sequencing and their susceptibility are reported in Table 1. #### Conclusions Rhizobium radiobacter, originally a member of the genus Agrobacterium, causes tumor growth in plants and is now recognized as a potential human pathogen. It is well established that CF patients are commonly colonized by a multitude of resistant pathogens providing a novel growth medium for R. radiobacter's promiscuous nature. Although from this case report it is difficult to assess R. radiobacter's impact on pulmonary function in CF, knowing that R. radiobacter has the potential to transfer genetic material to existing organisms, heightening their resistance and/or inducing tumor development, we present the first report of susceptibility characteristics for future utilization in CF. View this table: [Table44](/content/57/1/301/T44) R. radiobacter Antiobiotic Minimum Inhibitory Concentrations (ug/ml) ### 391 REGIONAL COMPARISON OF CAMPYLOBACTER EXPOSURES IN GEORGIA C. Beatty1,2, M. Tobin-D'Angelo1 * 1Georgia Department of Human Resources, Atlanta, GA and 2Emory University, Atlanta, GA* #### Purpose of Study Campylobacter is the most common cause of acute gastrointestinal illness in the United States. Variations in Campylobacter incidence have been observed both nationally and locally among FoodNet active surveillance sites. Georgia's incidence of Campylobacter infections is lower than the national average, yet certain areas of the state have a disproportionately high burden of cases. Campylobacter incidence rates in the northeastern and southeastern areas of Georgia have consistently been among the highest in the state for most years since 2000. Previous studies have identified consumption of chicken, poultry, unpasteurized dairy products or contaminated drinking water, recreational water exposure, and exposure to animals as risk factors for Campylobacter. Enhanced surveillance was carried out to examine exposures associated with regional variations in Campylobacter incidence in Georgia. #### Methods Used From Georgia FoodNet surveillance data, a convenience sample of confirmed Campylobacter cases was selected from high-rate Health Districts (>10 cases/100,000 population) and low-rate Health Districts (<5 cases/100,000 population) throughout the state. Sixty-five selected cases were interviewed to collect exposure and demographic data. Differences between high- and low-rate Districts were evaluated. #### Summary of Results Cases in high-rate Districts were more likely to live in a rural area (*P* < 0.01), and to have consumed well water during the week prior to illness onset (*P* = 0.03), than those in low-rate Districts. While not statistically significant, cases in high-rate districts were five times more likely to have had contact with farm animals (OR 5.08, *P* = 0.056). Living in low-rate Districts was most frequently associated with undercooked poultry consumption (*P* = < 0.01) and with travel (*P* = 0.02). #### Conclusions Persons infected with Campylobacter in high-rate Districts were more likely to live in rural areas where exposures to zoonotic reservoirs or water contaminated by animals would be more common. Those in low-rate Districts were more likely to have had a foodborne exposure or to have traveled. This suggests that Campylobacter infections in high-rate areas may be due to environmental, rather than foodborne, exposures. Additional research is warranted to further evaluate these differential exposures. ### 392 PERIPHERAL BLOOD CULTURE CONTAMINATION FROM A PEDIATRIC EMERGENCY DEPARTMENT T. Murillo1, T.M. Beavers-May2, D.L. English2, V.J. Plummer2, S.H. Stovall1,2 * 1University of Arkansas for Medical Sciences College of Medicine, Little Rock, AR and 2Arkansas Children's Hospital, Little Rock, AR* #### Purpose of Study Determine blood culture contamination rate (CR) in a pediatric ED, and identify factors associated with contamination. #### Methods Used A retrospective chart review was done to determine the CR of peripheral blood cultures from the ACH ED. Microbiology and patient records of patients with positive blood cultures were reviewed for organism, demographics, number of attempts, site, experience of the practitioner and follow-up care. The pre-intervention period (PRE) included cultures submitted between June 1 and November 30, 2007. An intervention for practitioners occurred in December 2007 and January 2008 requiring protocol review and supervised demonstration of technique on a simulated limb. Post-intervention period (POST) was February 1 through July 31, 2008. #### Summary of Results An average of 378 patients per month had blood cultures submitted during PRE. The positivity rate (PSR) was 6.8%, CR of 5.0% and pathogen rate (PR) 1.8%. An average of 418 patients had blood cultures submitted during POST with a PSR of 6.3%, CR of 4.9%, and PR of 1.4%. Contaminants represented 74% and 79% of positive cultures. 42% of patients in PRE and 48% in POST were discharged from the ED after submission of the culture. Of those, 23% and 24% then returned for repeat culture, antibiotic administration, and admission. The number of attempts to obtain blood culture was measured. In both PRE and POST, single attempts accounted for around 60% of contaminants. Individual practitioners who submitted more than 50 cultures in PRE and POST were evaluated for improvement in contamination rates. Seven improved CR to 0% while two had increased CR. Contamination rates were lowest in those patients greater than 13 years of age which was also the smallest number submitted. #### Conclusions The contamination rate in our ED for peripherally drawn blood cultures is around 5% each month. For each blood culture that results as positive there is a 75% chance the result is a contaminant that would not require treatment. Clinicians are not provided that information until more than 24 hours later resulting in unnecessary intervention. An intervention reviewing protocol was successful in reducing contamination rates from the most active practitioners. ### 393 PEDIATRIC INFECTIOUS DISEASE SPECIALISTS' MANAGEMENT OF ACUTE STAPHYLOCOCCAL OSTEOMYELITIS IN CHILDREN: AN IDSA/EIN SURVEY S.R. Arnold1, P.M. Polgreen2, S.E. Beekman2, S.C. Buckingham1 * 1University of Tennessee, Memphis, TN and 2University of Iowa, Iowa City, IA* #### Purpose of Study To determine the current management strategies of methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) acute hematogenous osteomyelitis (AHO) by pediatric infectious disease (ID) specialists. #### Methods Used Pediatric ID specialist members of the Emerging Infections Network (EIN) were surveyed regarding their management of staphylococcal AHO in children. Results reported are descriptive. Numbers in parentheses are the proportion of physicians selecting that response unless otherwise stated. #### Summary of Results 167 of 244 (68.4%) pediatric ID EIN members responded to the survey and reported seeing a median of 15 (range 0-76) AHO cases in the preceding year. 89% of respondents ranked MSSA and MRSA as the first or second most common etiology observed. Subperiosteal abscess was ranked the most common complication of staphylococcal AHO (76%); thrombophlebitis and pneumonia ranked second and third respectively. For MRSA AHO, clindamycin was selected the intravenous (IV) drug of choice by 57% respondents and vancomycin by 39%. Linezolid was the third line IV agent chosen (47%). Clindamycin was the most common oral agent used in MRSA AHO (89%). Linezolid (34%) and TMP-SMX (31%) were the most frequently used second line oral agents. Respondents were split on the use of oral stepdown therapy following an initial course of IV antibiotics. 28% of respondents reported using home IV therapy in >50% of cases. 59% of respondents used oral therapy in >50% of cases. 12% of respondents reported never using oral therapy. 44% of respondents who ever used oral stepdown therapy specified a minimum number of days of IV therapy prior to switching (median 7-10 days, range 0-28). 32% respondents reported seeing treatment failures in patients with staphylococcal AHO in the last 12 months using both the IV and oral stepdown therapy strategies #### Conclusions Among pediatric ID specialists, clindamycin is the most commonly used drug for MRSA AHO. Physicians are split on the use of oral stepdown therapy. With increasing rates of clindamycin resistance in MRSA, trials of alternative oral agents are needed to determine the optimal antimicrobial management of AHO in children. ### 394 VENTRICULAR SHUNT INFECTIONS: EFFECTS OF PERI-OPERATIVE ANTIMICROBIAL REGIMEN ON ETIOLOGY, SUSCEPTIBILITY AND RESPONSE TO TREATMENT J.R. Nichols1, S.H. Stovall1,2 * 1U. Ark. for Med. Sciences, Little Rock, AR and 2Arkansas Children's Hospital, Little Rock, AR* #### Purpose of Study The aim of this study is to describe the etiologies and circumstances surrounding ventricular shunt infections in pediatric patients at Arkansas Children's Hospital including peri-operative antimicrobial prophylaxis regimens. #### Methods Used Records of the infectious disease consult service were reviewed from 2003-2008 to identify 61 cases of ventricular shunt infection. Several variables associated with the clinical presentation and management of these infections were collected and reviewed. This study is IRB approved. #### Summary of Results The majority of the infections occurred in patients with ventriculoperitoneal shunts who were less than 1 year of age. Most patients had undergone shunt revision within 2 months prior to infection (72%). Patients presented with fever (70%), irritability (50%) and emesis (31%). Significant cerebrospinal fluid derangements were noted in many patients, including elevated WBC counts (>20) in 67% and elevated protein levels (>100) in 64%. Staphylococci were the most common causative organism, with 46% of infections caused by coagulase-negative staphylococci (CONS) and 18% by S. aureus. In the early study period (2003-2004), most patients received cefazolin for antibiotic prophylaxis. With the emergence of methicillin-resistant (MR) organisms, vancomycin became the most commonly used peri-operative antibiotic. Increasing numbers of infections caused by methicillin-susceptible (MS) organisms were observed in patients receiving vancomycin prophylaxis (23% MS-CONS, 23% MS-S. aureus in vancomycin patients vs. 0% MS-CONS, 12% MS-S.aureus in cefazolin patients). In addition, patients who received vancomycin prophylaxis were slower to resolve methicillin-resistant infections requiring vancomycin for treatment than those who received peri-operative cefazolin (2.7 days vs. 1.2 days). #### Conclusions Changes in etiology and antimicrobial susceptibility of ventricular shunt infections are temporally associated with shifts in peri-operative antimicrobial regimens. With the change to vancomycin as the preferred agent, methicillin susceptible Staphylococcus aureus infections have become more prevalent. Patients treated peri-operatively with vancomycin have been slower to resolve shunt infections despite appropriate therapy. ### 395 FACTORS ASSOCIATED WITH KNOWLEDGE OF HIV IN ECUADOR J.R. Olges1, B.S. Murphy2, A.R. Hoellein2, C.M. Hopenhayn3, T.L. Young4 * 1University of Kentucky, Lexington, KY; 2University of Kentucky, Lexington, KY; 3College of Public Health, University of Kentucky, Lexington, KY and 4University of Kentucky, Lexington, KY* #### Purpose of Study Although current HIV surveillance in Ecuador is limited, recent estimates suggest that the disease prevalence is increasing. Transmission has been observed through both homosexual and heterosexual contact, along with IV drug use. Factors contributing to the trend include political instability, a rise in poverty, a population shift from rural to urban areas and the migration of immigrants and drugs from neighboring Colombia. In order to avert a potential epidemic, appropriate preventative interventions need to be developed. This study presents an initial evaluation of baseline HIV awareness in the region, as well as the factors associated with this knowledge. #### Methods Used Surveys were administered to adult patients seen at the Centro Medico Hombro a Hombro clinic in Santo Domingo de los Colorados, Ecuador in August, 2008. Survey questions were designed to identify whether patients had ever heard of HIV/AIDS, and if so, whether they could name modes of transmission and ways to prevent the spread. Chi Square analysis and linear regression were conducted to identify possible predictors of knowledge. #### Summary of Results Over 18% of those completing the survey indicated that they had never heard of HIV or AIDS. Of those who reported to have heard of the disease, 19% were unable to name a way that the disease is transmitted, and 28% were not able to name a way to prevent the transmission of HIV. Gender, age, literacy and educational attainment were all individual factors which were shown to be associated with HIV awareness. #### Conclusions A significant number of individuals in Ecuador are still unaware of the HIV/AIDS epidemic. Even among those who have heard of the disease, many are unfamiliar with the modes of transmission and means of prevention. Previous studies in other developing countries have revealed results similar to ours, but few, if any, have examined HIV awareness in Ecuador. In addition to improved disease surveillance, it is critical to develop educational programs and public health interventions targeted at these vulnerable populations. ## **Perinatal Medicine II Concurrent Session** 1:00 PM Saturday, February 14, 2009 ### 396 ESCHERICHIA COLI MAY REDUCE APOPTOSIS IN THE INTESTINES OF IMMATURE MICE K. Cooper1, A. Berardinelli2,3, L. Ray2, A. Neish3, P. Lin2, * 1Spelman College, Atlanta, GA; 2Emory University School of Medicine, Atlanta, GA and 3Emory University School of Medicine, Atlanta, GA* #### Purpose of Study Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. Recent studies indicate that NEC is characterized by aberrant intestinal epithelial apoptosis during the initial stages of NEC development. Late NEC is manifested by severe necrosis of the intestine. In recent studies Lin, et al., demonstrated that administration of the probiotic *Lactobacillus rhamnosus GG* to immature mice reduces chemically-induced intestinal epithelial apoptosis in an *ex vivo* model. We hypothesized that another probiotic bacterium *Escherichia coli* could similarly prevent chemically-induced small intestinal epithelial apoptosis. This study aimed to determine whether *E. coli* prevents staurosporine-induced apoptosis in the small intestines of two week-old mice, *ex vivo*. #### Methods Used Two week-old mice were used to model premature human intestines. These immature mice were prefed media with or without 2-3 × 108 CFUs of a probiotic *E. coli* strain isolated from healthy human intestines. 24 hours later, immature murine intestines were isolated and programmed cell death was induced *ex vivo* by the apoptotic agonist staurosporine (1 μg/ml STS). Apoptotic cells were detected using terminal deoxynucleotidyl transferase (TUNEL) stain. Slides were viewed with a fluorescence microscope, and the number of TUNEL positive nuclei was counted per high power field (200x magnification). #### Summary of Results Small intestines excised from mice prefed *E. coli* prior to STS treatment exhibited fewer TUNEL positive epithelial cells when compared to similarly treated intestines from mice fed media alone. Control intestines isolated from media-fed or *E. coli*-fed mice exhibited minimal TUNEL positive staining if not subjected to subsequent *ex vivo* chemical treatment. #### Conclusions Small intestines from immature mice prefed *E. coli* prior to *ex vivo* STS treatment were less vulnerable to chemically-induced epithelial apoptosis. These results suggest that the probiotic *E. coli* may prevent NEC in babies by preventing apoptosis in developing intestines. ### 397 THE ROLE OF TOLL-LIKE RECEPTORS 2 AND 4 IN POSTNATAL INTESTINAL DEVELOPMENT P. Tatum1, E. Staley2, S. Tanner2, R. Lorenz2, R. Dimmitt1 * 1University of Alabama at Birmingham, Birmingham, AL and 2University of Alabama at Birmingham, Birmingham, AL* #### Purpose of Study Intestinal host-microbial interaction is mediated in part via toll-like receptors (TLR). We have recently shown that mice lacking TLR 2 have increased epithelial injury in an ischemia-reperfusion model of necrotizing enterocolitis (NEC). Studies have shown that premature infants receiving probiotic therapy have a decreased incidence of NEC. We hypothesize that early postnatal bacterial signaling through TLR 2 and TLR 4 is necessary for intestinal epithelial maturation and regulation of mucosal immunity, explaining the role of probiotic therapy in preventing NEC in humans. #### Methods Used Two week old C57BL/6 wild-type (WT), B6.TLR 2-/-, B6.TLR 4-/-, B6.TLR 2/4-/-, and antibiotic treated WT (microbial reduced, MR) received intraperitoneal bromodeoxyuridine (BrdU) 90 minutes prior to sacrifice. The small intestine was fixed in Bouin's solution and paraffin embedded. Proliferating cells were detected with an antibody to BrdU and slides were counterstained with H&E for structural histology. Two masked comparisons were made between the groups of mice with respect to the nuclear BrdU uptake, villus height, and villus number. Lymphocytes from mesenteric lymph nodes were isolated and stained with monoclonal antibodies to detect T cell activation by flow cytometry. Mice from the 5 groups were orally gavaged with FITC-dextran and serum was collected at time of sacrifice to determine intestinal barrier permeability. Parametric and non-parametric analysis was used as indicated with significance being *P* < 0.05. #### Summary of Results The median number of BrdU positive crypt cells in WT mice was significantly greater than in the TLR deficient and MR mice. In addition, the WT mice had taller, more numerous intestinal villi. The B6.TLR 2/4-/- mice had greater numbers of activated mesenteric CD4+ T cells (CD44+, CD69+, and CD25+). There was no difference in serum FITC-dextran concentration. #### Conclusions Mice lacking TLR 2 and 4 or that are devoid of bacteria have impaired early postnatal intestinal epithelial cell proliferation and villus development. These mice also have an increased pro-inflammatory mucosal immune activation. Probiotic signaling via TLR 2 and 4 may induce intestinal maturation and modulate the mucosal inflammatory response, thus preventing NEC. ### 398 EIGHT YEAR REVIEW OF GASTROSCHISIS IN KY (1998-2005) P.G. Radmacher *University of Louisville, Louisville, KY* #### Purpose of Study To analyze the incidence and geographic distribution of gastroschisis cases in KY. #### Methods Used Study was approved by the University of Louisville and the Cabinet for Health Services Institutional Review Boards prior to data release. Annual cases were provided by the KY Birth Surveillance Registry beginning in 1998. Birth certificate reports (initial sources) are individually verified by surveillance staff. Cases include both live and stillborn. Data on total births and stillbirths in KY were abstracted from annual vital statistics reports. Three maternal age cohorts were constructed: <20, 20-24 and >24 years of age. #### Summary of Results The 8-year incidence of gastroschisis in KY was 4.3/10,000 births (live and stillborn), compared to a national rate of ∼3/10,000. Forty-nine percent of the counties in KY have rates that exceed 4/10,000; 19 (15.8%) counties have a rate that exceeds 10/10,000. Rates are exceptionally high in the eastern part of the state where 11 of those 19 counties are found. Proportions of cases were nearly equally divided among mothers under 20 (37%) and those 20-24 years old (40%), although the incidence in each group was significantly different (12.1 vs. 5.6, *P* = 0.001). Together, these two age groups comprise over three-fourths of cases. Rates in mothers <25 were on a downward trend in 2003 and 2004. However in 2005, the rate more than doubled in the youngest mothers, from 5.9 to 14.9. There was a similar case distribution by sex (48.5% vs. 51.5%, male vs. female). Tobacco use among mothers of cases in all age groups was not significantly different (34.3%, 43.7%, 26.6%, ages <20, 20-24 and >24 respectively). These rates of tobacco use during pregnancy are significant when compared to the national average of ∼13%. #### Conclusions Gastroschisis is more common in KY compared to the national average. Specific regions of the state report exceptionally high rates. Tobacco use during pregnancy is 2-3 times higher than the national average. Rates in known susceptible age groups (women under 20) were on the rise in 2005. ### 399 TOTAL PARENTERAL NUTRITION-ASSOCIATED CHOLESTASIS IN EXTREMELY LOW BIRTH WEIGHT INFANTS M.C. Hitch, P. Radmacher, D.H. Adamkin *University of Louisville, Louisville, KY* #### Purpose of Study To define the natural history of cholestasis in ELBW infants in a university, level III nursery. #### Methods Used Case-control cohort of infants receiving parenteral amino acids within the first 24 hours of life. Thirty cholestatic infants (conjugated bilirubin >2.1 mg/dL) were matched with controls by BW ± 150 g and gestational age (GA)± 2 weeks. Inclusion criteria: birth weight (BW) <1 kg, admission to NICU <24 hrs after birth, TPN provided ≧5 days, survival ≧7 days. Exclusion criteria: Major congenital anomalies and surgery within the first 5 days of life. Data analyzed included patient characteristics and clinical course. Numeric data were analyzed by paired T-test; categorical data by Chi square. Mann-Whitney U test was used for non-normally distributed data. Statistical significance was set at *P* < 0.05. #### Summary of Results Cholestatic infants (CI) were lighter (683 ± 153g v. 752 ± 125g, (0.008)), more premature (25.4 ± 2.1 wk v. 26.2 ± 2.0 wk, (0.014)), and more ill than controls. These infants had higher SNAPPE scores (49.2 ± 18.4 v. 33.3 ± 14.6 (<0.001)), lower APGARS (6.3 ± 1.8 v. 7.4 ± 1.4 (0.017)), longer time on assisted ventilation (56 (38, 78) v. 38.0 (24, 38) days (0.003)), more likely to have IVH (53.30% v. 26.70% (0.032)), and required more days of Dopamine (6 (4, 9) v. 2 (1, 5) (0.002)). CI received more days of TPN (59.5 ± 79d v. 27.6 ± 13.6d (0.039)), were older when enteral feeds started (13.3 ± 8.6d v. 9 ± 5.2d (0.02)), had more days of central/peripheral access, and interruptions of feeding than control infants. Direct bilirubin levels were improving or normalized by discharge (3.5 ± 2.2 mg/dL). The CI mortalities all suffered from NEC and none had liver failure. #### Conclusions ELBW infants are at risk for TPNAC because of prematurity and associated complications. In this cohort of 30 children, conjugated hyperbilirubinemia had a self-resolving course. Most of the morbidity in these infants was early in life as indicated by SNAPPE score and hypotension and not from the use of TPN. The observed cholestatic infant mortalities were secondary to NEC and not liver failure. ### 400 THE EFFECT OF IMMUNE MODIFYING TREATMENT ON MORTALITY IN NEONATAL SEPTICAEMIA J.P. Kelleher, R.L. Schelonka *University of Alabama at Birmingham, Birmingham, AL* #### Purpose of Study Late onset neonatal sepsis is an important cause of death amongst infants within neonatal intensive care unit. Adjunctive treatment with recombinant granulocyte colony stimulating factor (rGCSF) and intravenous immunoglobulin (IVIg) may augment immune function and improve outcomes in critically ill, septic neonates. The purpose of this study was to determine whether rGCSF/IVIg treatment alters mortality in septic infants. #### Methods Used This study was a retrospective case control study of infants treated for culture-proven late onset sepsis in a large, urban regional neonatal intensive care unit during the years of 2003-2007. A registry of all septic infants was created concerning their microbiological treatments. Three specific groups of patients were identified within this registry. Group A featured those neutropenic and/or thrombocytopenic septic infants who did not receive rGCSF/IVIg. Group B included those septic infants who did not receive rGCSF/IVIg treatment and who were neither neutropenic and/or thrombocytopenic. Both groups A and B served as control groups for comparative analyses. Group C featured those septic infants who received rGCSF/IVIg. #### Summary of Results Infants who were not neutropenic/thrombocytopenic and who did not receive immune modifying treatment with rGCSF/IVIg had a lower mortality rate than infants who were neutropenic/thrombocytopenic (Table). #### Conclusions In our experience, septic infants who received immune modifying treatment with rGCSF/IVIg had significantly lower mortality rates than similarly ill infants who did not receive immune modifying treatment. These results support the need for an appropriately powered randomised controlled trial is needed to further investigate the role of rGCSF/IVIg in improving mortality for neonatal sepsis. ### 401 EFFECTS OF PRENATAL OXYCODONE EXPOSURE ON THE CARDIOVASCULAR RESPONSE TO ACUTE STRESS AND NEUROBEHAVIORAL OUTCOME IN THE OFFSPRING T. Sithisarn1, S. Barron2, K. Wellmann2, S. Legan3, H.S. Bada1, R. Charnigo4, D.C. Randall3 * 1U of Kentucky, Lexington, KY; 2U of Kentucky, Lexington, KY; 3U of Kentucky, Lexington, KY and 4U of Kentucky, Lexington, KY*. #### Purpose of Study Prenatal opiates exposure is associated with neurobehavioral changes regulated in part by the sympathetic-adrenal-medullary axis (SAM). Little is known of these effects of prenatal oxycodone (OXY) exposure. Objectives: To determine the effects of prenatal OXY vs. vehicle exposure on the offspring's (1) baseline blood pressure (BP) and heart rate (HR) (2) cardiovascular responses to acute stress and (3) open field behavior. #### Methods Used Pregnant rats were given i.v. OXY (2mg/kg) or vehicle (control, CON) daily from gestational day 8 to postnatal day (PD) 5. The pups were fostered to un-exposed dams on PD 5. 7 males from OXY and 7 from CON treated mothers were fitted with BP telemetry units (DSI PhysioTel PA-C10). Pups were classically conditioned by following a pulsed tone with tail shock (CS+). A steady tone (CS-) was never followed by shock. Their activity was also quantified for 30 min. daily for two days in an open field chamber on PD 50 using a video tracking system. Data were analyzed using 2-way ANOVAs. #### Summary of Results Mean baseline BP of OXY rats was (*P* < 0.05) higher than CON rats (118 vs. 115 mmHg). Time to peak BP increase after tone onset in OXY treated rats exceeded that in CON rats (CS +: OXY 15. 9 ± 0.3 vs. CON 15.7 ± 0.2; CS-: OXY 15.8 ± 0.1 vs. CON 15.5 ± 0.3 mil.sec.). Both groups distinguished between CS + and CS-, but the average HR change during the last 10 sec. of CS + was more pronounced in CON (OXY CS + 433 ± 13, CS- 443 ± 45; CON CS + 434 ± 21, CS- 453 ± 23 bpm). In the open field test OXY rats traveled a greater distance on the 2nd day of testing vs. CON. OXY rats also traveled less in the center zone of the open fields, suggesting greater anxiety like behavior. #### Conclusions Prenatal OXY exposure in male rats was associated with subtle alteration in SAM function during responses to acute behavioral stress. Hyperactivity and increased anxiety like behavior were also observed in exposed rats, similar to reports in human. Early changes in cardiovascular response to stress may indicate altered neurobehavioral outcomes. The mechanisms of these effects and whether the same changes occur in female offspring need further investigation. ### 402 DEXAMETHASONE DECREASES INSULINE-LIKE GROWTH FACTOR-I and -II IN THE NEONATAL RAT BRAIN A.J. Bhatt, Y. Feng, P.G. Rhodes *University of Mississippi Medical Center, Jackson, MS* #### Purpose of Study The use of Dexamethasone (Dex) in premature infants to prevent and/or treat bronchopulmonary dysplasia can adversely affect early neurodevelopment and probably result in loss of cerebral volume. Previous studies have shown that Dex is neurodenerative in newborn rat. The insulin-like growth factor-I (IGF-I) is a potent neurotrophic and neuroprotective factor. Insulin-like growth factor-II (IGF-II) also stimulates proliferation of both neuronal and glial cells, and neurite outgrowth. In addition, it acts as a survival factor for a variety of neuronal cell types. Previous studies have demonstrated that Dex usually down-regulates IGF-I. But, no information is available about the effect of Dex on IGF-I in newborn rat brain. The purpose of the current study was to evaluate the effect of Dex on IGF-I and IGF-II in the neonatal rat brain. #### Methods Used The Sprague-Dawley rat pups in each litter were divided into the vehicle or Dex-treated groups. Rat pups in the Dex group received tapering doses i.p. Dex on postnatal day 3 to 6 (0.5, 0.25, 0.125 and 0.06 mg/kg, respectively). One day after the treatment, IGF-I protein and mRNA expression of IGF-I and II were measured in the rat pup brain using ELISA and real-time RT-PCR, respectively. #### Summary of Results As shown in the figure, compared to vehicle, Dex decreased the expression of mRNA of IGF-I (∼0.56 fold, *P* < 0.01, n = 6), and IGF-II (∼0.32 fold, *P* < 0.01, n = 6) in rat pup brain. Brain IGF-I level was 4023.3 ± 102 pg/mg in the vehicle and 3287 ± 78 pg/mg in the Dex treated group (*P* < 0.01, n = 6/group). #### Conclusions We conclude that Dex significantly decreased IGF-I protein and the expression of mRNA of IGF-I and IGF-II in neonatal rat brain. We speculate that neurodegenerative effect of Dex in the developing brain may involve IGF-I and IGF-II signaling pathways. ![Figure.](/https://d3hme472k3gd2d.cloudfront.net/content/jim/57/1/301/F20.medium.gif) [Figure.](/content/57/1/301/F20) Figure.   ### 403 BIOMARKERS OF CEREBRAL INJURY IN A NEONATAL PIG MODEL OF CARDIOPULMONARY BYPASS AND CIRCULATORY ARREST AT 18°C and 25°C WITH AND WITHOUT SELECTIVE CEREBRAL PERFUSION T. Allibhai1, R. Digeronimo1, J. Whitin2, T. Yu2, J. Salazar3, M. Shoemaker1, H. Cohen2, P. Dixon1, A. Madan2 * 1Wilford Hall Medical Center, San Antonio, TX; 2Stanford University, Palo Alto, CA and 3Texas Children's Hospital, Houston, TX* #### Purpose of Study To determine the effects of 25°C HCA vs. standard 18°C HCA by comparing the protein profiles in cerebrospinal fluid (CSF) with those of control animals. #### Methods Used Immature Yorkshire piglets were assigned to one of four study groups (n = 5-8/group): (I) HCA at 18°C without SCP, (II) HCA at 18°C with SCP, (III) HCA at 25°C with SCP, or (IV) Control with no surgery. Surgical animals were placed on CPB and cooled to their assigned group temperature. They underwent 60 minutes of HCA, followed by 4 hours of recovery. SCP was provided via the innominate artery at a flow rate of 10 ml/kg/min. CSF was collected from anesthetized, age-matched control animals that did not undergo surgery and from surgical animals after recovery. CSF was treated with urea before binding proteins to weak cation exchange surfaces. Surface-enhanced laser desorption/ionization time-of-flight mass spectra were acquired and analyzed for differences between groups using the Wilcoxon rank-sum test. #### Summary of Results 194 protein peaks were detected. Compared to controls, Group I had 64 peaks, Group II had 100 peaks, and Group III had 13 peaks that were significantly different (*P* < 0.05). Comparing experimental groups to each other, Group II vs. III were most dissimilar, with 23 different peaks; whereas both had only a few different peaks vs. Group I (4 and 3 peaks, respectively). There were 7 peaks that were significantly different in all 3 surgical groups when compared to control (*P* < 0.05), 4 of which were elevated and 3 decreased. #### Conclusions Piglets exposed to CPB with HCA have significant alterations in the mass spectra of their CSF proteins. SCP during deep HCA at 18°C compared to 25°C results in more differences when compared to controls. Further analysis of altered CSF protein peaks may identify potential biomarkers to help determine optimal conditions for HCA to better limit neurologic injury. ## **Renal, Electrolyte and Hypertension II Concurrent Session** 1:00 PM Saturday, February 14, 2009 ### 404 ATHEROGENIC LIPOPROTEIN ABNORMALITIES ASSOCIATED WITH MILD ELEVATIONS IN URINE ALBUMIN EXCRETION AND IMPAIRMENT IN KIDNEY FUNCTION IN TYPE 2 DIABETIC SUBJECTS P. Ramirez1, H. Al-Shahrouri1,2, P. Fanti1,2, H. Abboud1,2, C. Lorenzo1, S. Haffner1 * 1University of Texas Health Science Center, San Antonio, TX and 2South Texas Veterans Health Care System, San Antonio, TX*. #### Purpose of Study Elevation in urinary albumin excretion rate and changes in glomerular filtration rate (GFR) are frequent complications of diabetes and are associated with increased risk of cardiovascular disease (CVD). Atherogenic lipoprotein abnormalities contribute to this increased CVD risk. The aim of this study is to investigate the relationship among albuminuria, estimated GFR (eGFR) and lipoproteins in the early stages of kidney disease in patients with type 2 diabetes. #### Methods Used We examined lipoprotein abnormalities as measured by conventional methods, nuclear magnetic resonance (NMR) spectroscopy, LDL size as measured by gel gradient, and apolipoproteins by immunoprecipitation in the Insulin Resistance Atherosclerosis Study (IRAS) a cross-sectional study. We included data from 517 type 2 diabetic men and women aged 40 to 69 years. Albumin to creatinine ratio (ACR) was used as a measure of urinary albumin excretion and 4 variable MDRD equation was used to calculate eGFR. #### Summary of Results 360 subjects had normal ACR, 131 had microalbuminuria, and 26 had macroalbuminuria. 475 subjects had eGFR >60 ml/min per 1.73m2 and 42 had eGFR between 30 and 60 ml/min per 1.73m2. No significant differences were seen in LDL, HDL, and LDL/HDL cholesterol with changes in eGFR and ACR when measured by conventional lipid profile. Smaller LDL size (*P* = <0.001) and higher concentrations of apoB (*P* = <0.001), apoB/apoA-I ratio (*P* = 0.001), total LDL particles (*P* = 0.028), small LDL particles (*P* = 0.002), and IDL particles (*P* = 0.007) were observed in subjects with elevated ACR. Reduced eGFR (<60 ml/min per 1.73 m2) was associated with increased total VLDL (*P* = <0.001), decreased total HDL particles (*P* = 0.027) and higher apoB/apo A-I ratio (*P* = 0.016). #### Conclusions In subjects with type 2 diabetes, mild elevations in albuminuria and mild impairment in renal function were associated with atherogenic lipoprotein abnormalities not apparent with a standard lipid panel. Therefore, NMR may be a useful tool in early detection and treatment of dyslipidemia, and prevention of cardiovascular disease in patients with type 2 diabetes. ### 405 TUBULO-INTERSTITIAL INJURY INDICATES INCREASED RISK FOR PROGRESSION OF MACROALBUMINURIC HYPERTENSIVE NEPHROPATHY A. Mahajan1, H. Rahjan2, S. Shearer3, J. Simoni4, D. Wesson1,5 * 1Texas A&M College of Medicine, Temple, TX; 2Texas A&M College of Medicine, Temple, TX; 3Scott and White Healthcare, Temple, TX; 4Texas Tech University Health Sciences Center, Lubbock, TX and 5Scott and White Healthcare, Temple, TX*. #### Purpose of Study Subjects with macroalbuminuric (urine albumin-to- creatinine ratio or alb/cr ≥200 mg/g) compared to non-macroalbuminuric (alb/cr <200 mg/g) hypertensive nephropathy (HN) have greater risk for progression to more advanced CKD stages despite ACE inhibition but only a minority do so (Warmoth, et al. AJMS 330:111, 2005). Because tubulo-interstitial injury (TII) characterizes HN, we tested the hypothesis that greater TII indicated by a urine TII index helps identify the minority of macroalbuminuric HN subjects at higher risk of progression to more advanced CKD. #### Methods Used We tested this hypothesis as a secondary outcome of a prospective, 5-yr study of 120 macroalbuminuric HN subjects with CKD stage 2 (eGFR 60 to 89, mean = 75 ± 1 ml/min) matched for age, eGFR, and alb/cr to determine if oral alkali reduced progression to CKD stage 3 (eGFR 30 to 59 ml/min). All were treated toward systolic BP <130 mm Hg with drug regimens including an ACE inhibitor. Each had yearly eGFR, alb/cr, and urine N-acetyl-β, D-glucosaminidase (NAG), the latter an index of TII, expressed as U per g creatinine. #### Summary of Results Of the 120 subjects, 107 completed the 5-yr follow-up and 14 progressed to CKD stage 3 (eGFR <60 ml/min). Five year systolic BP was similar (*P* = 0.9) but eGFR decline rate was faster in the <60 than >60 subjects (-3.9 ± 0.4 vs. -1.9 ± 0.1 ml/min/yr, *P* < 0.001). Higher initial urine alb/cr predicted increased risk for eGFR decline to < 60 (*P* < 0.011) as did higher initial urine NAG (*P* < 0.021). Initial urine NAG was higher in the <60 vs. >60 subjects (3.8 ± 0.2 vs. 2.5 ± 0.1 U/g, *P* < 0.001), increased during follow-up in the <60 subjects (to 4.4 ± 0.2 U/g, *P* < 0.001, paired t), but decreased in >60 subjects (to 2.4 ± 0.1 U/g, *P* < 0.001, paired t). #### Conclusions The data show that higher urine NAG, an index of TII, predicts greater risk for macroalbuminuric HN to progress from CKD stage 2 to 3 despite ACE inhibition. The data suggest that higher TII helps identify macroalbuminuric HN subjects who are at the greatest progression risk. ### 406 THE ASSOCIATION BETWEEN SILENT MYOCARDIAL ISCHEMIA AND KIDNEY DYSFUNCTION A. Almehmi1, J. Wetmore2, M. Broce3, A. Malas4 * 1Kansas University, Kansas City, KS; 2Kansas University, Kansas City, KS; 3CAMC, Charleston, WV and 4St Francis Hospital, Charleston, WV*. #### Purpose of Study To examine the relationship between kidney function and silent myocardial ischemia in patients undergoing coronary angioplasty. #### Methods Used This study included 243 patients who had undergone percutaneous coronary intervention (PCI). Silent myocardial ischemia was defined as the absence of chest pain in response to balloon dilatation of the affected vessel during PCI. A single operator documented the presence or absence of chest pain during PCI. GFR was estimated using the Modification of Diet in Renal Disease (MDRD) formula. Patients with GFR <60 ml/min/1.73 m were considered to have CKD. Student s t-test, Chi Square, Fisher's Exact and logistic regression were used to evaluate the relationship between angina and GFR. #### Summary of Results The study cohort included 64.2% men, 33.7% diabetics, and 35.4% current smokers, with mean age 64 ± 12 yr (mean ± SD), blood pressure 141 ± 25/76 ± 14 mmHg, LDL cholesterol 104 ± 33 mg/dL, and serum creatinine 1.1 ± 0.70 mg/dL. GFR in patients with CKD (30.5%) versus those without CKD (69.5%) was 46.6 ± 12.4 vs 89.7 ± 23.2 ml/min/1.73m (*P* = 0.0001), respectively. Absence of chest pain during angioplasty was reported more often in patients with CKD (37.7%) compared to those without CKD (23%) (*P* = 0.025). Multivariate analysis revealed that the absense of angina was associated only with the presence of CKD (defined as GFR < 60 ml/min/1.73m) (Odds Ratio, OR = 0.37, *P* = 0.003) and male gender (OR = 0.30, *P* = 0001). The absense of angina was not related to diabetes, history of CAD, hypertension, smoking, or hyperlipidemia. #### Conclusions The absence of chest pain had a strong and independent association with prevalent CKD, defined as GFR <60 ml/min/1.73m. A much higher proportion of CKD patients may have silent angina than those with GFR in the normal range. These findings may underlie the increased CAD mortality in patients with low GFR and invite further studies to determine the mechanisms by which renal dysfunction may influence the perception of chest pain. ### 407 URINE CYTOKINES PREDICT THE FUTURE REQUIREMENT FOR RENAL REPLACEMENT THERAPY IN PATIENTS WITH ACUTE KIDNEY INJURY E. Lewis1,2, T. Powell1, T. Taylor1,2, M. Mataria1,2, M. Budisaljevic1,2, M. Janech1,2, J. Arthur1,2 * 1Medical University of South Carolina, Charleston, SC and 2Ralph H. Johnson, VAMC, Charleston, SC*. #### Purpose of Study We hypothesized that urine cytokines and proteins along with clinical data can predict the need for renal replacement therapy in patients with acute kidney injury. #### Methods Used We collected urine from 104 patients with at least stage I acute kidney injury as defined by the Acute Kidney Injury Network criteria. Patients were followed to determine if they met the endpoint of either requiring RRT or attaining a peak serum creatinine of 6 mg/dL or greater. Twenty-two urine cytokines were measured using a Bioplex multiplexed bead array. Urine NGAL, Cystatin c and NAG levels were determined using commercially available assays. APACHE II scores were calculated for all patients based on clinical data available at the time of urine collection. All urine analytes were normalized to urinary creatinine concentration prior to analysis. #### Summary of Results Thirty patients progressed to dialysis and 74 did not. There was a statistical difference for some urine analyte concentrations and clinical data between the group that required RRT and the group that did not (No RRT). MCP-1, LIF, APACHE II score, NAG, IL-10, HGF, VEGF, Gro-α, NGAL, TRAIL, urine Cystatin c and IL-18 were significantly higher between the RRT and No RRT group respectively. We calculated the area under the ROC curve for the analytes that were statistically different between the groups. AUC values were: NGAL 0.78, APACHE II 0.66, IL-18 0.66, Cystatin c 0.65, NAG 0.64, IL-10 0.63, TRAIL 0.63, HGF 0.62, MCP-1 0.62, Gro-α 0.60, VEGF 0.60, and LIF 0.58. There was no difference in AUC values when the concentrations of analytes were normalized to urine creatinine. #### Conclusions These studies show that measurement of individual urine proteins can help predict the need for RRT. From among the most common AKI markers NGAL was the best at predicting the need for RRT followed by IL-18, cystatin C and NAG. Combinations of multiple proteins will likely improve the prognostic ability of the assay. ### 408 EFFECT OF TIMING OF INITIATION OF CONTINUOUS RENAL REPLACEMENT THERAPY ON RENAL RECOVERY R. Shingarev, A. Tolwani *University of Alabama at Birmingham, Birmingham, AL*. #### Purpose of Study The optimal time to initiate continuous renal replacement therapy (CRRT) in critically ill patients is unknown. The objective of this study is to determine whether the timing of CRRT based on a blood urea nitrogen (BUN) level affects renal recovery in intensive care unit (ICU) patients with acute kidney injury (AKI). #### Methods Used We retrospectively analyzed the data that was prospectively collected for 200 critically ill patients admitted to the single center who were started on CRRT for AKI. Patients were divided into early or late dialysis groups based upon whether the BUN was less than or greater than the median of 72.5 mg/dL. Standard logistic regression methods were used to account for selection effects. Renal recovery was assessed at both ICU and hospital discharge. #### Summary of Results The mean age was 62 years, CRRT initiation creatinine 4.2 mg/dL, BUN 75 mg/dL, and APACHE II score 26. AKI was attributed to septic shock in 51% of patients. Overall patient survival was 38%. Although crude data analysis showed no association between BUN levels and mortality, renal recovery rates were higher for patients who started CRRT at a lower BUN. No significant difference was found between CRRT dose, etiology of renal failure, days spent on CRRT, urine output, and presence of sepsis in the two groups. Adjusted for age, gender, CRRT initiation creatinine, hematocrit, presence of oliguria, intubation, and use of vasopressors, patients in the low BUN group had a higher rate of renal recovery compared to the high BUN group at hospital discharge (43 and 27%, p-value 0.007), but not at ICU discharge (40 and 25%, p-value ns). #### Conclusions Initiation of CRRT at lower BUN levels appears to offer a better renal prognosis for patients who survive ICU hospitalization. Randomized prospective studies are needed to validate these results. ### 409 PREDICTORS OF CHF IN A MANAGED-CARE CKD POPULATION M. Kats, I. Guessous, H. Wasse *Emory University, Atlanta, GA*. #### Purpose of Study It is well known that renal insufficiency is more prevalent in patients with congestive heart failure (CHF) and is an independent prognostic factor in diastolic and systolic dysfunction. However, the predictive factors for development of CHF in the setting of chronic kidney disease (CKD) are uncertain. #### Methods Used We analyzed data from the Kaiser Permanente Georgia CKD cohort comprised of enrollees between 1995-2007 who had a minimum of 2 estimated glomerular filtration rates (eGFR's) <90 ml/min/1.73 m2 that were more than 60 but less than 365 days apart. This analysis included only patients with an eGFR between 10-59 ml/min. CHF was defined by the presence of a CHF ICD-9 billing code at the time of cohort inception. #### Summary of Results Of the 14,922 eligible patients, 6.3% had a diagnosis of CHF. Those with CHF were older [68.4 versus 61.1 years (*P* < 0.0001)], and were more likely to be male [484 versus 457 patients (*P* < 0.0001)], had more advanced kidney disease [eGFR 44.5 versus 49.4 mL/min/1.73 m2 (*P* < 0.0001)], HTN [99.0% versus 73.0% (*P* < 0.0001)], diabetes [39.2% versus 22.1% (*P* < 0.0001)], CAD [44.9% versus 9.3% (*P* < 0.0001)], and PVD [12.5% versus 3.5% (*P* < 0.0001)]. Among patients with a claim-based diagnosis of CKD, the likelihood of being diagnosed with CHF was similar across GFR strata. However, among patients with a CKD diagnosis, the likelihood of a CHF diagnosis increased with worsening GFR. #### Conclusions Among CKD patients, CHF is more likely among patients with advanced kidney disease and cardiovascular risk factors. The likelihood of CHF is increased as GFR declines among patients without a claim-based CKD diagnosis. View this table: [Table45](/content/57/1/301/T45) Likelihood of Claim-based CHF diagnosis among Patients Lacking Claim-based CKD diagnosis ### 410 BACTEREMIA RATES IN HIV INFECTED HEMODIALYSIS PATIENTS: A COMPARATIVE ANALYSIS OF 1996 AND 2004 USRDS DATASETS H. Sakhamuri1, S. Maddirala1, S. Elfayoumy3, M. Htike3, P. Wludyka2, K. Britt1, C. Masnita-Iusan2, C. Heilig1, N.S. Nahman * 1University of Florida Jacksonville, Jacksonville, FL; 2University of N Florida, Jacksonville, FL and 3University of N Florida, Jacksonville, FL*. #### Purpose of Study Bac (BAC) is an important cause of morbidity and mortality in hemodialysis (HD) pts. We previously analyzed the DMMS dataset from the USRDS, and showed that HIV was a risk factor for BAC. These data predated the routine use of protease inhibitors (PI). In this regard, PI reduce morbidity and mortality from HIV. On this basis we theorized that BAC in HD patients with HIV would be improved after the introduction of PI therapy. #### Methods Used To test this question, we used multiple logistic regression analysis to compare the rates of BAC in HD pts between the DMMS (1996) and the USRDS from 2004 (2004). Both datasets were based on Medicare billing patterns for their respective time periods. #### Summary of Results The number of pts studied from each time period were 18,295 and 395,944 for 1996 and 2004, respectively. When compared to 1996, 2004 demonstrated a significant decrease in both the rate of BAC (16.5 vs 10.7%, *P* < 0.0001) and in the incidence of HIV (5.2 vs 2.4%, *P* < 0.0001). For HIV pts only, there was a significant decline in the rate of BAC in 2004 (22.3 vs 16%, *P* < 0.0001). Previous risk factors for BAC in HIV(+) HD pts include race, hepatitis C (HepC), and cirrhosis (CIR). The rate of BAC between 1996 and 2004 for HIV(+) pts was significantly greater in AA vs nonAA pts (18 vs 11.7% for 1996 vs 2004, respectively, *P* < 0.0001). There were no differences in BAC between the two time points for HIV(+) pts with HepC (30.2 vs 32.3%) or CIR (31.6 vs 32.5%). When controlling for race, HepC and CIR, the odds of BAC in 1996 vs 2004 was 1.591 (1.342 - 1.886, 95% CI). In summary, the rate of BAC in HIV(+) HD pts declined significantly between 1996 and 2004, and AA pts had a greater rate of BAC at both time points, despite a decline from 1996 to 2004 #### Conclusions BAC rates in HIV(+) HD pts improved between 1996 and 2004 and may in part be due to the introduction of PIs for the therapy of HIV disease, however the decline in BAC rate in 2004 for all pts suggests additional variables (such as improved infection control and/or vascular access hygiene) may also play a role. ### 411 IN VITRO CYTOTOXICITY OF GADOLINIM CONTRAST MEDIUM T. Qureshi, T. Nguyen, N.S. Nahman Jr, V. Urquidi *University of Florida College of Medicine Jacksonville, Jacksonville, FL*. #### Purpose of Study Gadolinim-based contrast medium is associated with the development of nephrogenic systemic fibrosis (NSF), a sclerosing dermopathy with a high rate of morbidity and mortality. The pathogenesis of NSF is unlcear, but has been postulated to be related to gadolinim-induced transmetalation in tissue, triggering an inflammatory and subsequent sclerosing response. It is unknown if the noxious effect of gadolinim is specific to fibroblastic cells or is a more generic cytotoxic event. To address this question, we investiged the cytotoxic effect of a gadolinum-based contrast medium in cultured epithelial and fibrobastic cell lines. #### Methods Used Epithelial (Hela cells) and fibroblastic cells (WI38 cells) were plated in triplicate for all conditions in 96 well plates. At confluence, the cells were washed, exposed to gadopentetate dimeglumine (Magnevist, Bayer) (Gad) or equiosmolar concentrations of mannitol (Man) (12mOsM, 25mOsM and 400mOsM). After 24 hours, all cells were harvested and cytotoxicity and cell viability measured using LDH release (CytoTox-one, Promega) and ATP content (CellTiter-Glo, Promega), respectivley. #### Summary of Results For Hela cells, there was a dose dependent increase in LDH release with both Gad and Man when 12mOsM was compared to 400 mOsM (164% vs 152% for Gad vs Man respectively). In contrast, W138 cells showed no change in LDH when 12mOsM was compared to 400 mOsM (265% vs 88% for Gad vs Man respectively). In VIA studies, Hela cells showed a drop in ATP content when 12mOsM was compared to 400 mOsM for both Gad and Man (6.8% and 0.4% for 400 mOsM vs 12mOsM for Gad and Man respectively). W138 cells showed a drop in ATP content when 12mOsM was compared to 400 mOsM for Gad, but not Man (2.5% and 76% for 400 mOsM vs 12mOsM for Gad and Man respectively). In summary, Hela cell toxicity of Gad may be related, at least in part to the osmotic effect of the compound. In contrast, W138 cells exhibited Gad toxicity independent of osmotic effect of mannitol, suggesting factors other than the osomotic effect may play a role in noxious responses to the agent. #### Conclusions In these pilot studies, there appears to be a lineage specific response to Gad with a fibroblastic cell line showing some features of toxicity that may be independent of the osmostic effects of Gad. ### 412 PHOSPHORYLATED AMP-ACTIVATED PROTEIN KINASE DURING EARLY DIABETIC NEPHROPATHY M.L. Lee1, K.W. McMahon1, V. Sood1, E. Beale2, S.S. Prabhakar1 * 1Texas Tech University Health Sciences Center, Lubbock, TX and 2TTUHSC-Paul Foster School of Medicine, El Paso, TX*. #### Purpose of Study The leading cause of chronic kidney disease is diabetic nephropathy (DN), yet its pathogenesis remains incompletely understood and current treatment options are not fully effective. Recently, it was reported that the activity of the AMP-activated protein kinase (AMPK) is down-regulated in DN, and has been linked to glomerular hypertrophy in DN. But the significance of AMPK in renal physiology and specifically in DN, is largely unknown. There are two isoforms of AMPK catalytic subunits expressed in the kidney, α1 and α2 subunits. The purpose of the present study is to examine the changes in the isoforms of AMPK catalytic subunits in early DN. #### Methods Used We studied the AMPK in ZSF rats, a recently-described model for nephropathy in type II diabetes. The rats were examined at 8 weeks, when they are phenotypically normal, and at 12 weeks, when hyperglycemia, obesity and albuminuria are established. Lean non-diabetic ZSF rats were used as controls. We separately immunoprecipitated the AMPK α1 and α2 subunits from the extracts of rat kidneys. These immunocomplexes were separated on SDS-PAGE, transferred to PVDF, and probed with antibodies specific to the phosphorylated form of AMPK. We also measured renal functional parameters in all rats. #### Summary of Results We observed that phosphorylation of the AMPK α1 subunit was diminished in the kidneys of obese rats relative to lean rats in early DN, while phosphorylation of the α2 subunit is not changed by DN. We also observed a decrease in the phosphorylation of Acetyl Co-A Carboxylase (ACC, a marker for AMPK activity). Together, these data indicate that the activity AMPK α1 is more affected than α2 by the early stage of DN. #### Conclusions We conclude that AMPK α1 activity decreased in early DN and this may potentially contribute to the pathogenesis of DN. View this table: [Table46](/content/57/1/301/T46) Characteristics of ZSF rats at 12th week ## **Southern Society of General Internal Medicine: Research Abstract Session** A 8:30 AM Friday, February 13, 2009 ### 413 EMERGENCY DEPARTMENT UTILIZATION AND HOSPITALIZATION AMONG HIV INFECTED PATIENTS: RELATIONSHIP TO OUTPATIENT APPOINTMENT ADHERENCE D.A. Morris, A. LaRocco *Eastern Virginia Medical School, Norfolk, VA*. #### Purpose of Study To determine whether non-adherence with outpatient appointments in addition to other risk factors, is an independent risk factor for emergency department use and hospitalization in HIV infected individuals. #### Methods Used Retrospective chart was conducted of 100 HIV infected patients over a 3-year time period receiving care from the Center for the Comprehensive Care of Immune Deficiency at Eastern Virginia Medical School. Data collected included number of ER visits, outpatient appointments, and hospitalizations as well as length of stay, interruptions in care, and markers of disease severity defined by CD4 counts and viral loads. Demographic data, insurance status, psychiatric diagnosis, alcohol abuse, and illicit drug use were recorded as well. Statistical analysis was performed to test the correlation between the numbers of ED visits and hospitalizations to measures of appointment compliance and interruptions in care. #### Summary of Results 54% of patients had a least one emergency room visit while 67% had no hospitalizations. Patients averaged 16 scheduled outpatient appointments and 10 kept outpatient visits during the study period. Only one individual kept all scheduled appointments while four missed greater than 75% of scheduled appointments. ER utilization correlated with the number of missed appointments (*P* 0.007) even when accounting for duration in care and disease severity. Hospitalization and length of stay was not predicted by number of missed appointments. Alcohol use did partially account for increased hospitalization and ED use (*P* 0.004). Likewise illicit drug users were more likely than their counterparts to use the emergency room (*P* 0.01). Unlike previous studies, breaks in care, ethnicity, gender, and disease severity, did not correlate with increased hospitalization or emergency room use. #### Conclusions A small portion of patients are missing a large number of appointments and using more services (i.e. ER, hospitalizations), but did not have more severe HIV disease. Substance abuse is a risk factor for missed appointments and ER use. Directing funds towards substance abuse and rehab efforts will assist this vulnerable group. Future studies are needed to examine co-morbidities in HIV infected patients, which may predict the patterns of ER use, hospitalization, and healthcare costs. ### 414 ANALYSIS OF CONTENT MASTERY ON THE INTERNAL MEDICINE IN- TRAINING EXAMINATIONS R. Nugent1, E. Ayers1, H. Wang2, M. Phy2, K. Nugent2 * 1Carnegie Mellon University, Pittsburgh, PA and 2Texas Tech University, Lubbock, TX*. #### Purpose of Study The internal medicine in-training examination provides information about residents' competence in medical knowledge and programs' educational curriculum. Exam results are summarized with percent correct answers and percentile standing of the residents. However, we can use specific content area results to compare the performance of subgroups of residents and characterize the relationships among content areas. #### Methods Used We used 2002-2007 in-training examination results (n = 160) for internal medicine residents at Texas Tech University in Lubbock, TX. Each resident was assigned a vector that measures competency on a [0, 1] scale for 11 content areas (i.e. 11 competency values). Values close to one indicate high competency. We used t-tests to determine statistically significant differences in content area mastery between subgroups of residents and correlations to describe the relationships among content areas. We then used multivariate clustering techniques to identify residents with similar competency patterns. #### Summary of Results Selected results are presented in this abstract. In 2007, international medical graduates (IMGs) and U.S. medical graduates (USMGs) were significantly different in cardiology competency (*P* = 0.06). Multivariate cluster analysis found two resident subgroups differentiated by a combination of high and medium competencies in general medicine, hematology, and pulmonology. Among first year residents, IMGs had higher competency than USMGs in cardiology (*P* = 0.10), hematology (*P* = 0.087), and rheumatology (*P* = 0.089). No content area differences were found by gender. The first year residents clustered into two combinations of high/medium cardiology, rheumatology, and infectious disease competencies. Similar analyses were done on third year residents. #### Conclusions Multivariate cluster analysis identifies differences in resident competency not found through univariate summaries. Characterizing these clusters by the residents' country and other covariates and analyzing content area relationships over time can provide insight into resident learning, more effective curriculum design, and content area relationships. ### 415 FIRST YEAR MEDICAL STUDENT PERSPECTIVES ON THE TRANSITION FROM CLASS TO THE CLINIC K. McKinney1,2, K. Moe3, J. Wilson1,3 * 1University of Kentucky, Lexington, KY; 2Veteran's Administration, Lexington, KY and 3University of Kentucky, Lexington, KY*. #### Purpose of Study Learning how to collect and organize patient information is a prominent facet of a medical student's transformation into a competent clinician. Medical schools provide formal instruction in interviewing techniques. However, the skill to accurately sort through information provided by patients is usually acquired informally and over time. This study analyzed medical students' reactions to their initial clinical experience as a first step in examining this process. #### Methods Used We examined writings in first year medical student portfolios composed as an assignment to reflect upon 25 hours spent in primary care or specialty outpatient clinics. Students were directed to record observations regarding their clinic visits, compose 2 essays highlighting a clinical situation of interest and reflect upon the "most important" aspects of their experience. A graduate student in the social sciences searched student reflections for expressions of uncertainty or lack of confidence related to the process of gathering and integrating information received from patients. The author then performed a secondary review of identified responses. Major themes were established via an iterative process and existed in the majority of student responses. #### Summary of Results 77 portfolios were available for screening and we examined a preliminary random sample of 45. Three major themes emerged. Students expressed difficulty absorbing the vast amount of patient information (written, verbal, anecdotal, and physical) presented in the clinical setting. They also struggled regarding how and whether to assign importance to non-medical information communicated by patients. Finally, students questioned the boundaries of appropriate dialogue with patients in relation to politics, spirituality, and cultural differences. #### Conclusions During their introduction to the role of a clinical trainee, medical students expressed difficulty filtering through the data presented in "real time" when seeing a patient. This finding highlights the importance of designing medical school curricula to not only teach interviewing techniques, but also to train students to accurately process information received in the patient interview. ### 416 PREDICTORS OF CONCORDANCE BETWEEN PATIENTS AND CENTERS FOR DISEASE CONTROL AND PREVENTION RECOMMENDATIONS REGARDING HUMAN IMMUNODEFICIENCY VIRUS SCREENING N. Lerfald1, M. Blackwell2, S. Sun3, I. Modak4 * 1West Virginia University, Morgantown, WV; 2Carolinas Medical Center, Charlotte, NC; 3Mount Vernon Hospital, New York, NY and 4Methodist Dallas Medical Center, Dallas, TX*. #### Purpose of Study Since 2006, the CDC has recommended HIV testing for all patients between the ages of 13 and 64. We report the frequency and predictors of agreement with this guideline as applied to adults (ages 18 to 64 years). #### Methods Used Patients from eight academic medicine clinics completed a 76-item survey. Included items were demographics, behavior, and HIV knowledge and attitudes. HIV knowledge questions were combined and evaluated as a scale. The primary outcome variable was agreement with universal HIV testing for the stated age range. Items that were predictive of agreement (*P* < 0.20 using bivariate analysis) were included as independent variables in a logistic regression model. #### Summary of Results 404 patients with a mean age of 45.3 years completed the questionnaire. 68% were female; 42% African-American, 15% Hispanic; 40% single, 25% with education 40) and more years of education also predicted agreement. Factors that were not predictive of agreement included race, gender, self-reported general health, and patients not wanting to be around someone with HIV. Risk factors for HIV were inconsistent in predicting patient beliefs. In the logistic regression analysis, the patients' physician having discussed HIV (OR 1.32, CI 1.01-1.71), and agreeing with screening for diabetes (OR 28.2, CI 10.4-76.6) remained independent predictors. #### Conclusions The strongest predictors of patient agreement with testing were having one's physician discuss HIV and agreeing with routine screening for diabetes. Encouraging physicians to discuss general information regarding HIV may improve acceptance of routine testing. Discussing it as part of an overall routine screening program may be particularly effective. ### 417 PERCEPTIONS OF THE INPATIENT TEAM: A QUALITATIVE ANALYSIS OF INPATIENT COMMENTS J.B. Romond1, D.M. Bhatt1, M.J. Lineberry2, A.R. Hoellein2, J.F. Wilson3, C.H. Griffith2 * 1University of Kentucky, Lexington, KY; 2University of Kentucky, Lexington, KY and 3University of Kentucky, Lexington, KY*. #### Purpose of Study Inpatient rounds at teaching hospitals represent a very complex care system with uncertain impact on patient satisfaction. This qualitative study examines inpatients' reflections about their team of doctors. #### Methods Used During a summer period, student research assistants observed teaching rounds of five Internal Medicine teams. Observers recorded the teams' activities, time devoted to each patient, team census, and delivered a 4-item, 5-point survey instrument using common measures of patient satisfaction. One of the items was open-ended, "My doctors here in the hospital are \___|." Responses were coded in an iterative process (JR, DB) using grounded theory approach with discrepancies resolved by a third coder (ML). #### Summary of Results A total of 64 teaching rounds with 11 different attending physicians were observed. The average census for each team was 10 ± 3. Average teaching rounds lasted 120.2 minutes, with 83.5 minutes devoted to patient care and 36.7 minutes of administrative time. Of 127 completed patient satisfaction surveys, total satisfaction was 4.38 ± 0.72, and 125 completed the open-ended item. Major themes to emerge included positive comments about the doctors' personality (43.2%), perceived knowledge base (12.8), verbal (9.6) and nonverbal (5.6) communication, and professionalism (8.0). Negative comments alluded to difficulties with interpersonal (2.4) and interprofessional (1.6) communication, appearing rushed (4.8) and even involved derogatory language (1.6) and allegations of incompetency (0.8). #### Conclusions We were pleased that the majority of the responses to our open-ended item were positive and note that personal traits are a powerful component of patient satisfaction. It is unsettling, however, that even a small percentage of our inpatients hold negative sentiments about the teaching team. We should strive to continuously hone our interpersonal and interprofessional communication and never appear rushed. Future research could further elucidate other variables that may be precipitating negative sentiments about the team as well as interventions to sharpen providers' communication skills. ### 418 WHAT IS THE DEMAND? INTERNET ACCESS TO A PRIMARY CARE OFFICE S. Gustafson, R. Kuriacose, S. Loyd, R.D. Smalligan *East Tennessee State University, Johnson City, TN*. #### Purpose of Study Communication with patients via the internet is being used in primary care offices with increasing frequency in hopes of improving satisfaction and efficiency. Obstacles to use of such methods include the fact that many patients do not have sufficient experience and comfort with the internet. This pilot study sought to determine baseline satisfaction with office communication and measure the demand for internet office access. #### Methods Used A convenience sample of patients at a university-based internal medicine clinic in TN was given an anonymous survey before an internet portal system was established. The questions assessed satisfaction with office communication and asked if patients would like to have internet access to the office. Demographic, computer use, and health information was also collected. The office staff was given a similar survey. Results were entered and percentages calculated using Excel. #### Summary of Results There were 154 patients, 38% male and 62% female with most between 41-70yo. Most patients had a high school education or some college and 45% earned less than $30k/yr. About 2/3 had internet access and half used the internet daily. Almost 3/4 of the patients stated that they would rather phone the office than use the internet, but 39-45% said they would use the internet to schedule appointments or ask for test results and prescription refills. Office staff responses were divided evenly with no preference for either phone or internet communication. About 3/4 of the office staff is currently satisfied with office communication. #### Conclusions Some studies show increasing patient interest in using the internet for communication with physician offices. The above results do not show a strong desire in our patient population for such access. This was an unexpected result since a majority of the patients have access to the internet and use it regularly. However, when asked specifically, many expressed desire to schedule appointments, get results and request refills by internet. The apparent low demand may be due to concern about an unknown internet system and concern from the staff about increasing the time spent on communication. A follow-up survey after the implementation of the internet system will show if patients and staff will use it and if there is improved efficiency or satisfaction with office communication. ### 419 RELATION BETWEEN DEPRESSION AND TENSION TYPE HEADACHE IN PATIENTS OF RURAL EL SALVADOR G. Valdez1, F. Aleman2, R.D. Smalligan1 * 1East Tennessee State University, Johnson city, TN and 2University of El Salvador, San Salvador, El Salvador*. #### Purpose of Study Headache is the sixth most common presenting complaint in ambulatory clinics in El Salvador. Previous studies have linked depression to functional somatic syndromes including tension type headaches. The aim of this study was to determine the frequency and severity of depressive symptoms in patients with tension headaches and its relationship with the subtypes of tension type headaches in a rural clinic in El Salvador. #### Methods Used Patients diagnosed with tension type headache based on International Headache Society (IHS) criteria in La Palma, El Salvador were first classified as chronic or episodic. Demographic and clinical data were collected and recorded in a structured format. A validated translation of Zung's Self-rating Depression Scale (SDS) was administered to each subject to determine the presence and severity of depression. Depression severity was divided into 4 categories per SDS guidelines: normal (score <50), mild depression (score 51-59), moderate (score 60 - 69), and severe depression (score >70). Odds ratios (OR) were then calculated based on demographic variables, headache subtype and depression severity and p values calculated. #### Summary of Results We evaluated 146 consecutive patients with tension type headache. Forty-six either declined to participate or met exclusion criteria. The final sample of 100 patients consisted of 91 women ranging in age from 15 to 71 and 88% were from rural areas. Fifty-two percent of the patients had chronic tension headaches and 48% had episodic. Depression was present in 84% of the sample overall. Depressive symptoms were present more frequently in patients with the chronic subtype of headaches compared with patients with the episodic subtype (OR: 10.29; CI 2.02 - 70.2). The mean SDS scores were higher in patients with the chronic subtype (58.6) compared with the episodic subtype (46.2). #### Conclusions Patients in this rural El Salvadoran clinic with the chronic subtype of tension headache were more likely to have depressive symptoms and their depression was more severe compared with patients with the episodic subtype of tension headaches. This study highlights the importance of recognizing tension type heachaches as a possible functional somatic symptom of an underlying depressive disorder. ### 420 GAIT SPEED VARIABILITY IN HEALTHY WORKERS H. Wang1, R. Alalawi1, R. Paige2, K. Nugent1, R. Raj1 * 1Texas Tech University Health Sciences Center, Lubbock, TX and 2Texas Tech University, Lubbock, TX*. #### Purpose of Study Gait speed measurements can predict future adverse events, especially in elderly patients. However, the variability in gait speed with repeated testing is uncertain, and the level of cardiac stress associated with short walks is uncertain. #### Methods Used We measured the gait velocity over a 100-foot course in 61 healthy volunteers. Each subject completed three trials in three separate sessions. There was a 3-minute recovery period following each walk. Pulse rates and O2 saturations were also measured. #### Summary of Results Sixty-one volunteers completed this study. The median age was 44 with a range of 20 to 70. Seventy-seven percent of the subjects were women. The mean BMI was 29.4 with a range of 19 to 53.2. Thirteen subjects had hypertension and nine had arthritis. Mean gait velocity was 4.17 feet/second with a range of 3.34 to 5.90. Gait speed in men equaled gait speed in women. Subjects with higher BMIs had slower gait speeds. Subjects with arthritis and subjects with more chronic medical problems had slower gait speeds. There were no important differences in the gait speeds within a given session or between sessions. The mean baseline pulse rate was 74 beats per minute. This increased to 90.5 beats per minute at the end of the walk tests and returned to baseline after a 3 minute recovery. The range of heart rate change was (+) 8 to (+) 29.6 beats per minute (based on mean values for individual subjects). The baseline O2 saturation was 97%, and this did not change significantly during the walk test. #### Conclusions Healthy workers have a wide range of gait speeds. This is explained in part by differences in BMI and by chronic medical conditions. There is little variability between trials within a session or between sessions. A one-hundred foot distance increases the heart rate approximately 16 beats per minute and almost all subjects return to their baseline heart rate within 3 minutes. Therefore, a 100-foot walk test provides sufficient stress to determine the effect of chronic medical conditions and BMI on gait speed and is reproducible enough to document changes related to medical intervention or disease progression. ### 421 FALLS AND CO-MORBID CONDITIONS AMONG NURSING HOME PATIENTS C. Caton1, E. Hill2, Y. Zhao1, W.P. Moran1 * 1Medical University of South Carolina, Charleston, SC and 2Medical University of South Carolina, Charleston, SC*. #### Purpose of Study BACKGROUND: In 2005, 1.8 million elderly Americans fell, of which 15,800 died as a result of their fall. For fatal falls in 2000, direct costs were reported at an estimated $0.2 billion, whereas $19 billion were reported for non fatal falls. Among nursing home residents, studies estimate that as many as 50% fall each year with a fall rate of 1.5 falls per bed and year. OBJECTIVE: To determine the association between co-morbid conditions and falls in elderly nursing home residents. #### Methods Used Data on 13,507 nursing home residents from the 2004, National Nursing Home Survey (NNHS) was analyzed. The outcome of interest was fall. The variables of interest were demographics, number of prescription medications, medical conditions, and ability to walk with or without assistance, ability to perform ADL's with or without assistance. Multiple logistic regression was used to assess the association between co-morbid conditions and the odds of falling adjusting for confounders. SAS callable SUDAAN was used to perform complex statistical analysis. #### Summary of Results 11,636 residents had data recorded on falls, and 37% had one or more falls. Overall, the majority of residents were white, previously married and female. Residents reporting a fall were older and took more medications than those reporting no fall (*P* < 0.05). Having a history of cardiovascular diagnoses, CVA, COPD and other lung conditions and musculoskeletal problems resulted in a statistically significant decreased odds of having a fall. Females had a decreased odds of falling OR 0.81(0.72, 0.90). Hispanic-whites and black residents both had statistically significant decreased odds of falling. Married residents were at increased odds of falling OR 1.27 (1.05, 1.54). Ability to walk without assistance and perform ADLs without assistance resulted in decreased odds of falling with OR 0.81 (0.76, 0.86) and OR 0.35 (0.21, 0.57) respectively. #### Conclusions This analysis confirms the association of previously described risk factors associated with falls. Using this information, nursing homes may use fall risk stratification techniques to focus safety measures on the population at highest risk. However, it is not clear that changing explanatory variables will result in reduced fall risk. ## **Southern Society of General Internal Medicine: Research Abstract Session B** 10:30 AM Friday, February 13, 2009 ### 422 RISK FACTORS FOR ANTIHYPERTENSIVE MEDICATION NON-ADHERENCE M.A. Hajjar1, M.M. Ray1, J. Tang1, J.Y. Wan2, J.E. Bailey1 * 1University of Tennessee Health Science Center, Memphis, TN and 2University of Tennessee Health Science Center, Memphis, TN*. #### Purpose of Study Little is known regarding the patient factors and health services exposures associated with improved adherence. This study seeks to determine the most important risk factors for antihypertensive non-adherence among Medicaid enrollees and whether increases in outpatient visits can improve adherence. #### Methods Used Secondary analysis of retrospective cohort study database of all chronic drug-treated hypertensives enrolled in Tennessee's Medicaid system for 3-7 years from 1994-2000. Demographic characteristics, comorbidity, health services and medication utilization were evaluated using administrative data during a 2-year baseline period. The study's main outcome measure was baseline antihypertensive refill adherence defined as the percentage of potential medication days for which medication was obtained. All subjects were categorized as either adherent or non-adherent using an 80% cutoff. Associations with non-adherence were assessed using logistic regression modeling. #### Summary of Results Using the 80% cutoff criteria, 60.6% (N = 29,970) of the 49,479 subjects were classified as non-adherent and 39.4% (N = 19,509) as adherent. For non-adherence, significant variables (*P* < 0.05) in multivariate analysis included: age (Odds Ratio = 0.97), male gender (1.12), black race (1.67), disability (0.62), urban residence (1.12), obesity (1.10), diabetes (0.76), mental illness (1.08), substance abuse (1.43), hypercholesterolemia (0.72) and Charlson Index (0.97). When health care utilization was considered, increases in outpatient visits were associated with decreased risk of non-adherence (Odds Ratio = 0.99), while emergency visits (1.07) and hospital visits (1.12) were associated with increased odds of non-adherence. #### Conclusions This study demonstrates that substance abuse, mental illness, black race, emergency visits and hospitalizations serve as potent risk factors for non-adherence and that increases in outpatient visits are associated with improved adherence. An increase by one outpatient visit was associated with a decrease in odds of non-adherence by 1%. This suggests outpatient visits can help improve adherence in patients at risk. This strategy merits further evaluation through clinical trials. ### 423 INTERNSHIP 101: EVALUATION OF A NEW INTERDISCIPLINARY 4TH YEAR STUDENT ELECTIVE E. Brownfield1,2, J. Ondo2, J. Wong1,2, L. Manfred1,2, B. Bozarth2, A. Beddingfield2 * 1MUSC, Charleston, SC and 2MUSC, Charleston, SC*. #### Purpose of Study In order to fill perceived curricular gaps and promote self-assessment among students, we launched a new CME-style 4th year elective and evaluated the extent to which student-identified goals were met. #### Methods Used A working group designed a CME-style course two weeks in length offered twice in the spring. We solicited some courses and sent an open invitation to the faculty of the colleges of medicine, pharmacy, allied heath and nursing. Students registered their schedules electronically choosing sessions from an on-line catalog. The course was graded pass/fail based on attendance of 25 session hours within the 2 week period, and evaluated by students electronically. Retrospective focus groups generated additional information. #### Summary of Results Faculty and residents from 2 universities, all 4 colleges within the medical university and 10 departments participated. A total of 46 separate sessions were offered, most of which were repeated for each 2 week session. Eighteen sessions were recruited by the working group, and 28 resulted from the call for submissions. Fifty-four students registered for the course, an additional 12 audited portions of the course, and 7 students received the evaluation in error resulting in the return of 73 total evaluations. Results are presented in the attached table. Fifty-one of 52 students responding would recommend the course to colleagues. Students and faculty in the focus groups liked the course, thought it filled particular gaps in the curriculum and the personal education of our students. They recommended that many sessions be incorporated into the regular curriculum. #### Conclusions The inaugural run of a 4th year medical student elective covering numerous subjects in disparate formats was attended by approximately 40% of the class, and students felt that their learning goals were met. Future directions include scheduling changes to address session overlap and the inclusion of parts of the course in the yearlong curriculum. View this table: [Table47](/content/57/1/301/T47) Evaluations of Internship 101 ### 424 WHO YOU GONNA CALL? ETHNICITY-BASED VARIATION IN TRUSTED SOURCES OF HEALTH INFORMATION C.L. Martin1, R.A. Pope1, T.F. Cutts2, L.R. Sprabery1, J.E. Bailey1 * 1University of Tennessee Health Science Center, Memphis, TN and 2Methodist Healthcare, Memphis, TN*. #### Purpose of Study This study examines variation by ethnicity in trusted sources of health information. Our hypothesis was that a person's primary and most trusted sources of health information vary by ethnicity. #### Methods Used This cross-sectional study used data from a survey of 512 randomly selected African American and white adults in a mid-sized metropolitan area. Frequencies were compared by the Chi-square test of independence. Statistical significance was assumed when the *P*-values were equal or less than 0.05. #### Summary of Results Blacks are more likely than whites to seek news from television, and whites are more likely to seek news from newspapers. For health news TV is the primary source for most people, and newspapers are the second most common source. Blacks are more likely than whites to rely on TV for health news, and whites are more likely than blacks to rely on newspapers. Most (91.2%) people trust their doctor's judgment about their medical care with no difference between blacks and whites in their trust of health messages received from their doctor or healthcare professional. Blacks place more trust than whites in information received from their place of worship, TV, and newspapers. #### Conclusions Individuals and organizations that communicate health messages should consider their target audiences when selecting the media they will use. Information reaches more people through television than through newspapers, radio, family members, co-workers, friends or neighbors. Health messages via TV reach more blacks than whites, and messages via newspapers reach more whites than blacks. View this table: [Table48](/content/57/1/301/T48) ### 425 USING VIDEO IMAGES FOR ADVANCE CARE PLANNING: WHAT PARTICIPANTS THINK K. Murphy1, A. Hunter1, A. Volandes2, K. Deep3 * 1University of Kentucky, Lexington, KY; 2Harvard Medical School, Cambridge, MA and 3University of Kentucky, Lexington, KY*. #### Purpose of Study Video images illustrating advanced dementia can significantly change patients' preferences for future medical care. This study explores patients' perspectives on the use of video in eliciting preferences for future care. #### Methods Used Subjects recruited from primary care clinics were asked their preferred level of care (life-prolonging, limited, comfort, or uncertain) if they had advanced dementia. They were then shown a video of advanced dementia and again asked for their preferred level of care. We analyzed responses of participants who changed their preferred level of care following the video. They were asked how the video affected their understanding of the disease condition and how videos of patients with other diseases might be helpful. Three independent raters developed a coding scheme and applied it in an iterative process with discrepancies resolved by consensus. Codes were not mutually exclusive and one response could receive multiple codes. #### Summary of Results A total of 120 participants at 2 medical centers completed the study. The mean age was 58±12 years and 69% were women. Sixty respondents initially chose comfort care and none changed after seeing the video. Of the 60 subjects who did change their preference for care, 88% stated that the video was very helpful. Content analysis from the interviews of these 60 participants revealed three main themes: "seeing is believing," acquiring knowledge, and appealing to emotion. Twenty-three participants (38%) found inherent value in actually seeing the patient with the disease. Thirteen participants (22%) gained substantive knowledge about the disease process itself. Another 13 participants (22%) acquired knowledge about the quality of life of the patient, while 5 learned about the effects on the caregiver. Nine participants experienced an emotional response to the video which affected their preferred level of care. #### Conclusions Video is an acceptable and educational intervention to better inform patients. It most often affects decision making by providing a visual link to the patient's experience. Participants also report that video offers knowledge not imparted with verbal descriptions and conveys emotional content that is helpful for decision making. ### 426 ARE CDC HIV SCREENING GUIDELINES OVERCOMING BARRIERS TO TESTING? S. Holliday1, N. LaVine2, J. Morris3, N. Lerfald4, M. Landry5 * 1The Ohio State University, Columbus, OH; 2St. Vincent's Medical Center, New York, NY; 3University of Alabama at Birmingham, Birmingham, AL; 4West Virginia University, Morgantown, WV and 5Tulane University, New Orleans, LA*. #### Purpose of Study In the US 488,861 patients are estimated to be HIV + (2006 CDC). Early diagnosis and care of HIV patients improves survival. To improve early HIV detection and survival and decrease transmission rates, the CDC released new guidelines in September 2006 for one-time screening of all adults, regardless of risk factors. #### Methods Used Physicians at 8 academic medical center residency clinics were surveyed about HIV screening practices and attitudes. A random sample of physicians was invited to participate at each institution. The questionnaire included demographics, knowledge of CDC guidelines, perceived barriers to HIV testing and post-guideline screening habits. A "Practice Score" (pscore) was created for each respondent based on self-reported screening discussions with patients meeting the CDC testing parameters (pscore α = 0.91). A tabulation of reported barriers was created for each respondent, generating a "barrier score" (α = 0.8) for the number of barriers the physician felt inhibited screening efforts - including time constraints, not knowing patient risks, burdensome processes, and discomfort issues. #### Summary of Results 218 physicians responded (84% response rate). Only 7% of physicians reported screening patients meeting the CDC's recommended age range "frequently" or "always". Adding the "sometimes" response only garnered 50%. Regression analysis of barrier score and pscore showed that there was a significant association between the perception of barriers to screening and the omission of HIV screening discussions with patients (*P* = 0.00). This association was not affected by PGY year or attending physician status. #### Conclusions Despite CDC recommendations to screen all patients 18 to 64, physicians still report barriers. These barriers reflect actual practice with very low adoption of the guidelines. The data suggest physician understanding of the guidelines remains an issue two years after their release. More physician education and/or alternative strategies that enhance patients' screening initiative or redesign of clinic screening systems are needed to improve screening rates. ### 427 UNDERSTANDING OF CLEAR LIQUID INSTRUCTIONS AS PART OF COLONOSCOPY PREPARATION S. Paranjape, N. Nickl, L. Selby *University of Kentucky, Lexington, KY*. #### Purpose of Study Complete bowel preparation is key for visualization during colonoscopy. Poor preparation is common and often attributed to patient noncompliance, though patients may have simply not understood the prep regimen. Our goal was to evaluate patients' comprehension of the clear liquid part of colonoscopy prep instructions since this aspect of the prep process is common to most regimens regardless of cleansing agent. #### Methods Used While awaiting their procedures, we asked patients and their companions to fill out a 10 question survey that asked subjects how the prep instructions were presented to them, how long ago this occurred, and if they understood the instructions. Other information included: age, gender, education level, and past experience with procedures that required clear liquids. They were asked to correctly choose the clear liquids from a list of 24 foods and beverages. Scoring was calculated as follows: # correct - # incorrect/ total # possible correct answers x 100. #### Summary of Results 203 subjects completed the study, 114 patients and 89 companions. The mean age of both groups was 54%. 27% of patients and 31% of companions had a 9th -12th grade education. 54% and 60% had a college/post-graduate education respectively. 72% of patients and 65% of companions had a prior procedure with clear liquid instruction. 92% of patients and 52% of companions said they understood the instructions. 36% of patients and 22% of companions selected clear liquids from the list of food/drink items with > or = 80% accuracy. We compared the association of accurately selecting clear liquids > or <80% of the time and if the subject selected a non-clear item with: 1) education > or <12th grade, 2) report of understanding prep instructions and 3) receipt of similar procedure in the past using the Fischer exact probability test. #### Conclusions Although our study is small, we feel the sample size is clinically relevant. There is no statistically significant correlation of patients' level of education, self-report of instruction comprehension, or past procedure experience with how well they select a clear liquid from a list of food items. We hypothesize that many patients have a poor prep because they do not understand clear liquid instructions. Further research into the causes of poor comprehension and methods to improve understanding is important for future study. ### 428 LET'S BE POSITIVE: USING PATIENT CARE EXPERIENCES TO PROMOTE CHANGE E. Erlandson1, D. Bhatt1, M. Mendoza1, J. Pinnick1, C. Hustedde2, D. Rudy3 * 1University of Kentucky, Lexinton, KY; 2University of Kentucky, Lexinton, KY and 3University of Kentucky, Lexinton, KY*. #### Purpose of Study Improving patient satisfaction has become very important in healthcare organizations. Appreciative Inquiry (AI) may be useful in promoting behaviors to accomplish this goal. This interview-based approach gathers information about positive experiences. We propose that identification of positive experiences in patient care might lay the foundation for change in the future. Shifting the focus from what is wrong to what is right about patient care should engage and energize people to create positive change. The purpose of this study is to use AI to identify positive aspects of patient care at our institution. #### Methods Used Patients and employees were asked to recall a time when they received, were are part of, or witnessed excellent personal care, identify persons and their attributes that contributed to the occurrence and what their wish would be for future improvement. Transcripts of the interviews were analyzed for thematic categories by two reviewers in an iterative process. The responses were then coded for the presence or absence of the themes. Discrepancies were resolved via consensus. #### Summary of Results Twenty-three interviews were completed. The themes identified included: attentiveness by the provider (44%), compassion (22%), the professional nature of the patient-provider interaction (22%), commitment to service (13%), and teamwork (4%). The characteristics of the person(s) involved which contributed to the excellent care included: compassion (48%), helpfulness (43%), and professional demeanor (13%). Of the twenty wishes, nine (45%) focused on comprehensive patient care, six (30%) on excellence in medical treatment, and five (25%) wished to improve the physical environment of the hospital. #### Conclusions The prevailing theme is that excellent patient care is based in positive relationships both between patients and providers and between providers. This includes personal qualities such as attentiveness, compassion, helpfulness, commitment to service, and cooperation. To help improve patient satisfaction efforts should be focused on promoting personal qualities and an environment that fosters positive relationships. ### 429 ACHIEVING UNIVERSAL HIV SCREENING-PREDICTORS OF WHAT INFLUENCES SCREENING J. Martinez1, M. Stefan2, K. Crawford3, S.W. Su4, I. Modak5 * 1Weill Cornell Medical Cntr, NY, NY; 2Baystate Medical Cntr, Springfield, MA; 3Moses Cone Health System, Greensboro, NC; 4Mount Vernon Hospital, NY, NY and 5Methodist Dallas Medical Cntr, Dallas, TX*. #### Purpose of Study Over 1,000,000 persons in the US are living with HIV/AIDS, with 24% unaware of their HIV status. In 2006, the CDC recommended universal HIV screening. However it remains unclear who is being routinely screened for HIV. This study seeks to evaluate the characteristics of patients that are being tested compared to who are not. #### Methods Used Patients were recruited from 8 academic internal medicine clinics. Patients were eligible if they were 18-64 years old, fluent in English or Spanish and received continuity care at the clinic. Participants completed a 76 item survey which assessed demographics, HIV risk factors, knowledge, beliefs, attitudes and characteristics of patient-MD interactions. An HIV knowledge score was generated. Descriptive statistics were complied. Bivariate analyses were performed and variables with a p-value of <0.1 were included in a logistic regression model to determine characteristics most associated with HIV screening. #### Summary of Results From the 404 patients who completed the surveys 60% (218 patients) reported being screened for HIV. 68% were female, mean age was 45.3, and majority was of ethnic minorities (67%). In the bivariate analyses, MD recommendation (93% of those tested), patient's own request (95%), younger age (mean age 43 for those tested), more knowledge about HIV and HIV screening, knowing someone with HIV (69%), agreement with CDC recommendations (86%), being comfortable with their doctor (88%), using street drugs in less than 5ys (82%) were strongly associated with testing. In logistic regression, MD recommendation (OR 5.36), if they knew someone with HIV (OR 2.68), agreement with the CDC recommendations (OR 5.1) and patients' asking for the test (OR 53.6) remained significant. #### Conclusions Although per the 2006 recommendations all patients in our cohort should have been screened for HIV, only 60% reported being screened. This rate is far better than past reports. Our data suggest that a patient request is the strongest predictor of HIV screening. Therefore, simple waiting room prompts and public education campaigns may represent the most efficient interventions to approach CDC universal HIV screening goals. ## **Southern Society of General Internal Medicine Research Abstract Session** C 1:30 PM Friday, February 13, 2009 ### 430 WHAT DO PATIENTS WANT WHEN IT COMES TO HIV TESTING, AND ARE DOCTORS LISTENING? N.A. LaVine1, J.L. Morris2, S. Holliday3, J. Martinez4 * 1St. Vincent's Medical Center, New York, NY; 2University of Alabama at Birmingham, Birmingham, AL; 3The Ohio State University College of Medicine, Columbus, OH and 4Weill Cornell Medical Center, New York, NY*. #### Purpose of Study Despite 2006 CDC Guidelines recommending universal, opt-out testing, doctors and patients continue to have difficulty communicating successfully when it comes to HIV screening. Understanding patients' wishes concerning HIV testing and physicians' perceptions of these wishes might contribute to better adherence to the CDC guidelines. We performed a multi-center study to assess these issues. #### Methods Used We recruited a systematic sample of resident and attending physicians who see patients and/or teach at general internal medicine clinics at nine different academic medical centers. Each physician anonymously answered a 90 item survey of their knowledge, attitudes and practices regarding HIV screening and their patients. Patients at the same centers were also anonymously surveyed regarding their knowledge of HIV, attitudes towards testing, and their relationship with their physicians in a 76 item questionnaire. Preliminary data are reported from eight sites. #### Summary of Results Of 404 patients surveyed, 54% of patients reported that they have asked to be tested for HIV. Yet 55% of 218 physician respondents reported that 5 percent or less of their patients request HIV testing. Only 28% of patients report that their doctor has specifically recommended that they be tested for HIV in an environment where 85% of physicians reported that they themselves would be willing to be tested. #### Conclusions Despite improvements in HIV knowledge and education over the last two decades, there continues to be a major disconnect between individual patients' willingness to be tested for HIV and doctors' perception of this willingness. This disconnect continues to lead to less testing then patients perceive as appropriate. Since doctors appear to have difficulty ascertaining patients' wishes in regard to HIV testing, adherence to universal HIV screening as suggested by the 2006 CDC guidelines would be a logical step in overcoming this barrier. Therefore, physician education and systems-based changes that operationalize these guidelines are indicated. ### 431 WEB-ANALYTICS: CHANGES OF PARTICIPATION MEASUREMENT C. Estrada1,2, P. Krishnamoorthy2, A. Smith2, L. Staton3, T. Houston1,2 * 1Birmingham VAMC, Birmingham, AL; 2The University of Alabama at Birmingham, Birmingham, AL and 3University of Tennessee College of Medicine Chattanooga, Chattanooga, TN*. #### Purpose of Study Participation in online educational activities usually decreases over time; measuring participation may guide recruitment. We explored whether participation changed over time in an online cultural competence curriculum. #### Methods Used In the first month, the URL was distributed to organizations focusing on cultural diversity or CME or cardiovascular disease, and to attendees at a national workshop. We measured use on four areas: **a)** *Web* (number of visits), **b)** *engagement* (number of pages per visit), **c)** *traffic sources* (how users came to the site), and **d)** *CME requests*. We used Urchin Software 5.0 (Google Analytics) to analyze Web server log files. #### Summary of Results *Web use:* site was visited 1,738 times; average length was 2min 34sec. Number of pages viewed/day and number of visits/day increased since site was launched (mean pages/day for each month 48.5, 84.2, 90.5, 168.5; mean visits/day for each month, 4.6, 10.3, 8.7, 25.8; both *P* < 0.001). *Engagement:* although not statistically significant, the number of pages viewed/visit declined (10.0, 7.4, 9.9, 6.8; *P* = 0.32). *Traffic sources:* of 1,738 visits, the main site was accessed directly in 687 (40%), by referral from search engines in 548 (32%), by referral from a site with a link to the online curriculum in 449 (26%), and others in 54 (3%). Of the 548 visits resulting from search engines, the search terms were related to cultural issues in 29%, to cardiovascular disease 9%, to medications 41%, and to other terms 21%. *CME was requested* by 72 participants, 66% physicians, 8% residents, 7% medical students, and 19% others; 24 requested CME once, 24 twice. The number of CME requests varied for each month since launch (25, 14, 29, 4). #### Conclusions While participation increased in month 4, after extensive posting of the URL, engagement per visit tended to decline. CME was requested by a small proportion of visitors to the site, suggesting that the user did not need or want CME (either clinicians or non-clinicians), or that the content was not relevant. Participation measurement of web-based educational curricula can determine how users interact with the site. ### 432 INPATIENT SATISFACTION ON TEACHING TEAMS A.R. Hoellein1, M.J. Lineberry1, C.A. Feddock1, J.F. Wilson2, C.H. Griffith1 * 1University of Kentucky, Lexington, KY and 2University of Kentucky, Lexington, KY*. #### Purpose of Study Inpatient teaching rounds have been the cornerstone of medical education for decades. This is a very fragile environment, however, with multiple variables that may negatively impact a key clinical outcome, patient satisfaction. #### Methods Used During a summer period, student research assistants observed teaching rounds of five Internal Medicine teams. Observers recorded the teams' activities, time devoted to each patient, team census, patient complexity scores, and delivered a 4-item, 5-point survey instrument using common measures of patient satisfaction. Descriptive statistics, Pearson and Spearman correlations, and Multiple regression (GLM) were analyzed with SAS Version 9.1. #### Summary of Results 64 teaching rounds with 11 different attending physicians were observed. The average census was 10±3. Average teaching rounds lasted 120.2 minutes, with 83.5 for patient care, and 4.2 per patient spent at the bedside. Of 127 completed patient satisfaction surveys, total satisfaction was 4.38±0.72. While team census was negatively associated with patient satisfaction (r = -.22, *P* = 0.014), patient sequence was positively associated with chances of both perfect satisfaction and good satisfaction, see Table. Patient sequence was not associated with patient complexity (*P* = 0.51). Time spent at the bedside by the team was not associated with total patient satisfaction (*P* = 0.24), but was associated with the likelihood of having perfect satisfaction (52% vs. 29%, *P* = 0.05). #### Conclusions Patient satisfaction is subject to many variables and our data imply a possible impact by the team census and order the patient was seen on teaching rounds. We hypothesized patients seen later in rounds might sense a certain level of hurry to complete rounds on time and therefore be less satisfied. The data show otherwise, even when solved for measures of patient complexity, a significant trend worthy of further research. View this table: [Table49](/content/57/1/301/T49) Patient Sequence and Satisfaction ### 433 PREPARING FOR SCIENTIFIC PRESENTATIONS: HOW DO YOU PRACTICE? E.D. Snyder1,2, A. Castiglioni1,2, A. Salanitro1,2, C. Estrada1,2 * 1University of Alabama Birmingham, Birmingham, AL and 2Birmingham VA Medical Center, Birmingham, AL*. #### Purpose of Study Scientific presentation skills are required in academic medicine and residency training. Little is known about practice and mentoring for these presentations. In this study, we sought to categorize presenters' practice styles and the impact of feedback received. #### Methods Used After the Southern Society of General Internal Medicine (SSGIM) 2008 annual meeting, we sent presenters an e-mail invitation to anonymously complete a 10-item web based survey. Presenters were asked: 1) the frequency and settings of practice prior to the presentation; 2) the type of feedback perceived as most helpful; 3) the changes presenters made in response to feedback; and 4) comfort level with the presentation both before and after feedback (5-point Likert scale: 1 = Very Uncomfortable, 5 = Very Comfortable). #### Summary of Results Representing 10 institutions, 47% (21/45) completed the survey, 16 of whom were trainees. Seven presented oral abstracts, 13 oral clinical vignettes, and 1 presented a poster. All responders had practiced in some amount prior to presenting at the meeting (33% >6 times). Presenters practiced in a mean of 2.7 different settings (range 1-5). The most common settings were practicing alone (81%) and sending slides to a mentor (76%). Practicing in front of a group of more experienced colleagues was perceived as the most helpful (43%). Responders reported a mean of 3.3 types of changes made to their presentations after practice (range 0-8). The most commonly made changes were to graphics (52.4%) and delivery style (48%). Comfort level improved after practice from a median of 3 (Q1-Q3: 3-4) to 4 (Q1-Q3: 4-5) (*P* < 0.001)(Q1 = 25th tile, Q3 = 75th tile). #### Conclusions Presenters for the 2008 SSGIM meeting practiced and received feedback in a variety of ways, and practice seemed to improve comfort level with the presentation. However, the most common practice settings, presenting alone and sending slides to a mentor, may not be the most helpful. Residency programs and academic divisions should provide more formal venues for practice and feedback. If particularly helpful types of practice and feedback become the standard, presentation quality may improve. ### 434 PREVALENCE OF VITAMIN D DEFICIENCY IN AN URBAN GENERAL INTERNAL MEDICINE ACADEMIC PRACTICE M.M. Ray, A.N. Long, D. Nandikanti, K. Lamar, T. Hughes, P. Adams-Graves, B. Williams-Cleaves *University of Tennessee Health Science Center, Memphis, TN*. #### Purpose of Study The increasing prevalence of vitamin D deficiency (VitDD) in the general U.S. population has gained national attention. We have randomly screened for VitDD (25-hydroxy vitamin D ng/ml) at the University of Tennessee Health Science Center in a general internal medicine practice (GEN) to confirm data already collected in a Sickle Cell Disease (SCD) practice and an Endocrinology practice (ENDO). The goal of our study is to document and raise awareness of the prevalence of VitDD. #### Methods Used Random screening of vitamin D levels were performed over an 18 month period. We divided VitDD into four categories: severe (<7 ng/ml) moderate (7.0-20.9 ng/ml) mild (21-31.9 ng/ml) and sufficient (>32 ng/ml). There were 1217 patients (714 GEN, 376 ENDO and 127 SCD); 870 African-Americans (AA), 322 Caucasians, 2 Italians, 3 Hispanics, and 20 other; 335 males and 882 females. The average age was 57 for the GEN patients, 36 years for the SCD patients and 59 years for the ENDO patients. Descriptive statistics were calculated. T-tests and analysis of variance procedures were performed to compare deficiency levels by race, gender, age and population. #### Summary of Results The majority of GEN patients randomly screened for VitDD were deficient (87.3%); with only 12.7% sufficient. In the three groups, 27.8% were severely deficient, 58.9% were moderately deficient, 12% were mildly deficient and 1.3% was sufficient. AA patients had higher frequencies of VitDD compared to other races; with a higher frequency of sufficient vitamin D levels observed in Caucasians. Female patients had a significantly higher frequency of VitDD compared to males. VitDD also differed significantly by age in an inverse relationship. #### Conclusions The prevalence of vitamin D deficiency among this population was higher than reported in literature. Based on preliminary data analysis, we believe that a greater percentage of the general population needs to be studied in order to discover the true prevalence of vitamin D deficiency. Our lead investigators are therefore proposing a campus-wide survey to help us further define the extensiveness of this disorder and to begin to look for mechanisms that may help us to further determine the factors associated with this widespread and growing condition. ### 435 RESIDENT PHYSICIAN CENTRAL VENOUS LINE PLACEMENT TRAINING REDUCES CENTRAL VENOUS LINE ASSOCIATED BACTEREMIA AT PITT COUNTY MEMORIAL HOSPITAL S. Kraemer, K. Ramsey, M. Mazer, W. Robey *East Carolina University Brody School of Medicine, Greenville, NC*. #### Purpose of Study To decrease CVL-associated BSIs at PCMH following institution wide training of the resident physicians on CVL placement. #### Methods Used PGY1 internal medicine, emergency medicine, and surgery residents completed a Graduate Medical Education Office sponsored 3 step sequential central line training program in January 2007. Session #1 requires completion of the DICON web based course. Session #2 occurs within the simulation lab for instruction and practice of subclavian and internal jugular CVL insertion. Step 3 consists of an Observed Clinical Skills Exercise during which residents simulate communication skills required for informed consent for CVL placement. The institution also promotes compliance with CVL bundles and the use of a CVL insertion procedure note. These initiatives predated the CVL resident training. CVL-associated BSIs were detected during the 2006-07 and 2007-08 fiscal years using the NNIS definitions, were calculated housewide with the CVL-associated BSI rates per 1000 line days. These data were compared with the BSIs for fiscal year 2005-06. #### Summary of Results Since the initiation of this standardized training, CVL-associated BSIs declined from 5.21 per 1000 line days, to 3.51 per 1000 line days and 4.56 per 1000 line days, for the 2006-07 and 2007-08 fiscal years respectively. #### Conclusions The CVL insertion resident training program has contributed to a decrease of CVL infections and maintenance of improved rates of CVL infections at PCMH. CVL training promotes a standardization of technique and mandated use of quality bundles. This quality initiative is one of the first GME education programs revealing a link between resident education and improved patient outcomes within an entire institution. ### 436 PATTERNS OF CERVICAL CANCER SCREENING AMONG INTERNAL MEDICINE RESIDENTS P. DePuy1, A. Cherrington1, E. Boohaker1, E. Snyder1,2 * 1University of Alabama at Birmingham, Birmingham, AL and 2Birmingham VA Medical Center, Birmingham, AL*. #### Purpose of Study Cervical cancer screening is fundamental in the primary care of women. Our aim was to assess how often Internal Medicine (IM) residents perform cervical cancer screening as well as the perceived barriers to cervical cancer screening in primary care. #### Methods Used We administered a cross-sectional survey to IM residents at the University of Alabama at Birmingham. Residents were asked about the frequency with which they perform cervical cancer screening on eligible patients, the factors that limit screening, and their level of interest in additional training regarding cervical cancer screening. #### Summary of Results Seventy residents completed questionnaires (n = 70); 74% of participants were male and participation was spread evenly across PGY level. The majority of residents planned to pursue a medical sub-specialty (76%), 6% planned to enter a primary care field, and 19% were undecided. Among all residents, 21% reported "Never" performing pap smears. Among residents entering or considering primary care, 18% reported never performing pap smears, while among residents planning to sub-specialize, 23% reported never performing pap smears. The most common reasons for not performing cervical cancer screening included: "Don't have time" (26%), "Dealing with too many issues" (24%), and "Patient already has Ob/Gyn" (24%). Among residents planning a primary care career, 15% also listed "Don't feel like can get good sample" as a reason not to perform screening, only 6% of those planning to sub-specialize listed that as a reason. Forty-five percent of residents were interested in improving competency in cervical cancer screening; that number was higher among residents planning or considering primary care careers (63%). #### Conclusions The majority of IM residents surveyed perform cervical cancer screening at least sometimes. Nearly half of residents would like to have more training, with more interest being expressed by those considering primary care. IM residencies should design and promote additional opportunities to enhance training in cervical cancer screening for interested residents. ### 437 PHYSICIAN KNOWLEDGE OF THE REVISED HIV SCREENING GUIDELINES J.L. Morris1, S. Holliday2, N.A. LaVine3, M. Stefan4, * 1University of Alabama at Birmingham, Birmingham, AL; 2The Ohio State University College of Medicine, Columbus, OH; 3St. Vincent's Medical Center, New York, NY and 4Baystate Medical Center, Springfiled, MA*. #### Purpose of Study At the end of 2003, an estimated 300,000 people were living with undiagnosed HIV in the United States. In September 2006, the CDC released revised guidelines for HIV testing based on analyses that demonstrated the cost-effectiveness of early diagnosis and treatment. Two years after the CDC published recommendations for universal HIV screening, we examine physician knowledge of these guidelines. #### Methods Used Resident and attending physicians from Internal Medicine and Medicine-Pediatric resident clinics at 7 academic medical centers were surveyed about HIV screening practices and attitudes. A random sample of physicians was invited to participate from each institution. The questionnaire included items about demographic information, screening habits since the CDC guidelines were revised, self-reported knowledge of CDC recommendations and perceived barriers to HIV screening. An HIV screening knowledge score was calculated for each respondent by assigning one point for each correct answer and 0 points for each incorrect answer or blank response. Linear regression was used to determine which factors were predictive of a higher HIV screening knowledge score. #### Summary of Results 218 physicians (170 residents and 48 attending physicians) completed the survey. The mean HIV screening knowledge score was 6.1 (SD 0.22) of a possible 11. Of the 218 respondents, 36% reported familiarity with the 2006 CDC guidelines for HIV screening and 28% were able to correctly answer >80% of the knowledge questions. In the regression analyses, variables associated with a higher HIV screening knowledge score were attending physician status (*P* = 0.00), female gender (*P* = 0.00), and self-reported familiarity with the CDC guidelines for HIV screening (*P* = 0.09). #### Conclusions The findings suggest that Internal Medicine residents and faculty physicians have limited knowledge of the 2006 CDC guidelines for HIV screening. Attending physicians have better knowledge of the guidelines, but a significant knowledge gap exists between the teachers and their learners. More emphasis needs to be placed on the CDC screening guidelines and HIV screening rates in Internal Medicine Teaching Clinics. ## **Southern Society of General Internal Medicine Research Abstract Oral Plenary Session** 8:00 AM Saturday, February 14, 2009 ### 438 HEALTH HABITS OF PRIMARY CARE TRAINED PHYSICIANS J. Blair-Elortegui1,2, L. Sawyer2 * 1University of South Alabama, Mobile, AL and 2University of South Alabama, Mobile, AL*. #### Purpose of Study The purpose of this study was to describe the health habits of primary care trained physicians at a university hospital. Primary care physicians (PCP) routinely provide counseling to patients about their health habits. This study sought to explore if PCPs model the behaviors they recommend to patients. #### Methods Used An IRB approved, anonymous, online survey was emailed to PCPs, residents and mid-level providers in Internal Medicine, Family Medicine, Pediatrics, and Internal Medicine-Pediatrics. Questions were based on the CDC's Behavioral Risk Factor Surveillance Survey. Additional questions were added to better define the specific population studied. Descriptive statistics were used to examine the overall responses. Comparisons were made for different subgroups. #### Summary of Results 107 of 179 PCPs completed the survey for a response rate of 60%. The majority of respondents were Caucasian (64.5%), married (76.6%), and age 26-35 years (59.8%). Respondents were relatively equally divided between males/females and resident/attending physicians. Although 67% had a routine dental visit, only 26% had a routine medical check-up within the last year. 45% of respondents did not have a PCP. Of the 35% that had a chronic medical condition requiring medication, 25% never took their medication as prescribed. Respondents were up to date on flu and tetanus vaccines >70% of the time. 94% were abstinent from cigarettes. Only 31.7% participated in exercise 3 or more times per week. Conversely, 76.9% consumed fast food weekly and 44.3% consumed sugar sweetened beverages daily. Those working greater than eighty hours weekly were more likely to be obese (average BMI 32.6 kg/m2 vs. average BMI 25.6 kg/m2 overall.) #### Conclusions Physicians are subject to many of the health concerns seen in patients including medical non-compliance, lack of routine preventative medical care, unhealthy dietary practices, and obesity. Many factors may contribute to these issues such as demanding work schedules, stress, and work-life imbalance. More complex factors such as the ability to provide self treatment and discomfort with seeking care from a peer may also be contributors. Improved physician health habits could not only improve physician health and productivity, but have a positive impact on patients by behavior modeling. ### 439 MULTIPLE UNCONTROLLED COMORBID CONDITIONS AND MEDICATION INTENSIFICATION A.H. Salanitro1,3, E. Funkhouser1,3, J.J. Allison1,3, J.H. Halanych3, T.K. Houston1,3, M.S. Litaker1,3, D.A. Levine2, M.M. Safford3 * 1Birmingham VA Medical Center, Birmingham, AL; 2Ohio State University, Columbus, OH and 3University of Alabama at Birmingham, Birmingham, AL*. #### Purpose of Study Multiple uncontrolled comorbid medical conditions (MUCC) in the same patient may act as competing demands for clinical decision-making. We hypothesized that MUCC decreases the likelihood of blood pressure (BP) medication intensification among uncontrolled hypertensive patients. #### Methods Used After each encounter made by 946 patients in a VA Medical Center primary care clinic, clinicians recorded whether BP medications (meds) were intensified (new med added or existing med titrated). Research assistants recorded patient age, sex, BP, and last HbA1c and low density lipoprotein cholesterol (LDL-C) levels. "Uncontrolled" was defined for BP as >140/90 mmHg or >130/80 if diabetic; for diabetes as HbA1c>7%; and for lipids as LDL-C >130 mg/dl or >100 if diabetic. Hierarchical regression models examined factors associated with BP med intensification, accounting for clustering. #### Summary of Results Patients had mean age 62+SD13, 3.1% were female, 424 (45%) presented with uncontrolled BP, 158 (17%) with uncontrolled diabetes, and 210 (22%) with uncontrolled lipids; intensification rates for the 424 patients with uncontrolled BP are in the Table. Among the 424 patients, adjusting for patient age, BP level, and clustering by clinician, odds of BP med intensification increased as MUCC rose (odds ratio of med intensification for BP+1 was 1.40 (95%CI: 0.97, 2.02) and for BP+2 was 2.72 (1.32, 5.58), compared with BP+0). Stratifying on median SBP revealed similar MUCC effects in both groups. #### Conclusions Providers appropriately managed hypertension more aggressively in patients with MUCC. Contrary to our hypothesis, MUCC actually enhanced guideline-concordant hypertension care. Performance measures must advance beyond simple dichotomous thresholds to examine appropriate decision-making, especially among complex patients. View this table: [Table50](/content/57/1/301/T50) BP med intensification rates by number of MUCC and SBP ### 440 PATIENTS' HIV KNOWLEDGE IN 2008: PREDICTORS OF POOR KNOWLEDGE AND SUCCESS OF PUBLIC HEALTH EDUCATION EFFORTS M. Blackwell1, N. Lerfald2, S. Wu Sun3, I. Modak4 * 1Carolinas Med Center, Charlotte, NC; 2WVU, Morgantown, WV; 3Mt Vernon Hosp, New York, NY and 4Methodist Hosp, Dallas, TX*. #### Purpose of Study Two decades of public health campaigns have tried to improve the nation's knowledge of HIV. The most recent measure of these efforts was the 1992 National Health Interview Survey (NHIS). We report current HIV knowledge, compare data to the NHIS, and identify predictors of poor knowledge among patients. #### Methods Used Patients from 8 academic clinics completed a 76-item survey on demographics, behavior, and HIV knowledge. Three knowledge scores were calculated: one for HIV spread and prevention, one for HIV treatment and prognosis, and an aggregate score. Descriptive statistics were compared to NHIS data. Bivariate analyses were performed, and a logistic regression model was constructed using HIV knowledge score as the outcome variable. #### Summary of Results 404 patients with a mean age of 45.3 years participated. Of those, 68% were female, 42% African-Amer, 15% Hispanic, 40% single, 25% with edu < high school, and 63% with income <$20K/year. The mean knowledge score for HIV spread and prevention was 12.4 (SE 0.15) out of 14. The mean score for HIV treatment and prognosis was 4.8 (SE 0.6) out of 6. The mean total score was 17.2 (SE 0.19) out of 20. Although knowledge regarding HIV spread by casual contact was higher than on the NHIS, 9% answered HIV could be spread by hugging, 10% by shaking hands, 18% by sneezing, and 33% by kissing. Compared to the NHIS, knowledge on the existence of HIV medications was higher, but more respondents incorrectly answered that there was a cure for HIV. One-fourth thought HIV life expectancy is <5 years and ∼50% did not identify HIV as a chronic disease. After regression analysis, a lower total knowledge score was associated with not completing high school (OR = 1.7, *P* = 0.002). Variables associated with a lower treatment and prognosis score include not knowing someone with HIV (OR 1.7, *P* = 0.001) and not completing high school (OR 1.2, *P* = 0.04). No significant differences were noted based on age, gender, race, marital status, or HIV risk factors. #### Conclusions Deficits in knowledge, particularly regarding spread of HIV by casual contact and prognosis after HIV infection, remain. Public health efforts should target these issues and people with fewer years of formal education. ### 441 FACTORS SURROUNDING PHYSICIAN-PATIENT DISCUSSIONS ABOUT HIV AND THE IMPACT ON TESTING M.R. Crawford1, M. Stefan2, J. Martinez3, M. Blackwell4 * 1Moses Cone Health System, Greensboro, NC; 2Baystate Medical Center/Tufts University School of Medicine, Springfield, MA; 3Weill Cornell Medical Center, New York, NY and 4Carolinas Medical Center, Charlotte, NC*. #### Purpose of Study Prior to the 2006 CDC guidelines regarding universal HIV screening, surveys revealed that physicians did not consistently screen for HIV. It is not known how well screening correlates with physician initiated discussions concerning HIV testing. If we can understand how well the message of universal HIV screening is communicated to patients, we can improve HIV testing rates. The purpose of this report is to evaluate factors influencing patient reported discussions about HIV with their physicians. #### Methods Used Patients were enrolled at 8 academic internal medicine clinics as part of a multi-site study examining HIV screening rates. Patients were eligible if they were age 18-64, fluent in English or Spanish, and in receipt of continuity care. Participants completed a 76-item questionnaire, which included demographic questions and knowledge assessment about HIV. Our primary outcome variable was patient-physician discussions about HIV. Bivariate analyses were done examining the association between patient age, gender, race, income, perceptions of trust and physician accessibility, and rates of self-reported HIV testing with this outcome. #### Summary of Results Of 404 respondents, 361 completed survey questions regarding physician discussions about HIV. Of these patients, 44.6% stated that their physician discussed how HIV is spread, how to avoid HIV, and who should be tested for HIV. Patients were more likely to be non-white (52 vs 33%, *P* = 0.001), younger than 40 (53 vs 39%, *P* = 0.01) and of a lower income strata (49% < $20K vs 38% > $20K, *P* = 0.04). Whether patients had the discussion or not, they trusted their physician and felt that their physician listened to them. Intuitively, physicians were more likely to recommend testing if they discussed HIV with their patients (68 vs 36%, *P* < 0.001), and those patients were more likely to be tested (58 vs 26%, *P* < 0.001). #### Conclusions Despite universal HIV screening guidelines, differences remain in patient populations with whom physicians discuss HIV. These discussions translate into more testing; therefore, interventions that improve communication regarding screening must be explored. ### 442 MEDICAL STUDENTS AND PATIENT CARE TIME E.E. Lampson1, M.J. Swadley1, M.J. Lineberry2, J.F. Wilson3, C.H. Griffith2, A.R. Hoellein2 * 1University of Kentucky, Lexington, KY; 2University of Kentucky, Lexington, KY and 3University of Kentucky, Lexington, KY*. #### Purpose of Study Inpatient teaching rounds have been the cornerstone of undergraduate and graduate medical education for decades. The presence of medical students has been shown to increase the value of teaching rounds for trainees but their effect on patient care is less well understood. #### Methods Used During a summer period, four student research assistants observed teaching rounds of five Internal Medicine teams over 26 days. Observers recorded the teams' activities and time devoted to each patient as well as each team's patient census and presence or absence of a medical student on the team. Data were analyzed with SPSS© 16.0. #### Summary of Results A total of 64 teaching rounds with 11 different attending physicians were observed. The average census for each team was 10 ± 3. Medical students were part of the teaching team on 28 (44%) of observed rounds. Average teaching rounds lasted 120.2 minutes, with 83.5 devoted to patient care and 36.7 minutes of administrative time. When medical students were present vs. not, total rounds time and administrative time were not significantly longer (133.1 vs. 110.2 minutes, *P* = 0.052 and 36.7 vs. 36.7, *P* = 0.992, respectively) but time devoted to patient care increased (96.4 vs. 73.5, *P* = 0.022). The mean total amount of time spent on each patient case was 9.8 minutes, with means of 2.4 devoted to presentation of the case, 3.2 dedicated to discussion, and 4.2 spent bedside. When a medical student was on the team, more time was devoted to presentation of the patient (3.0 vs. 2.0 minutes, *P* = 0.001) and discussion of the case (3.9 vs. 2.7 minutes, *P* = 0.004). Bedside time was preserved regardless of student presence (4.5 vs. 4.0 minutes, *P* = 0.166). #### Conclusions It is interesting that the presence of medical students on a teaching team added little time to the basic components of rounds, only increasing time devoted to case presentation and discussion. Intuitively, novice learners, i.e., medical students, need more time to present patient cases and contribute to more detailed discussion. Future research could investigate whether the extra time spent on patient care improved those patients' outcomes. ### 443 EXPLORING THE PREFERENCES AND DECISION-MAKING OF PATIENTS USING VIDEO IMAGES OF ADVANCED DEMENTIA A. Hunter1, K. Murphy1, A. Volandes2, K. Deep1, * 1University of Kentucky, Lexington, KY and 2Harvard Medical School, Boston, MA*. #### Purpose of Study Recent evidence suggests that video images illustrating advanced dementia can significantly change patients' preferences for medical care when imagining future health states. This study examines how video changes the rationale for patients' decision-making. #### Methods Used Patients over age 40 were recruited from primary care clinics at two study sites. They were first provided a verbal description of advanced dementia, asked their preferred level of care (life-prolonging, limited, comfort, or uncertain) and the rationale for their preference. They were then shown a brief video of a patient with advanced dementia and were asked again for their preferred level of care and their rationale. Three independent raters performed thematic analyses using an iterative process of the pre- and post-video reasoning for participants whose choice of care changed following the video. The code list was applied by all three raters with discrepancies resolved by consensus. #### Summary of Results Of the 120 subjects, 60 initially chose comfort care and their preferences did not change after the video. Life-prolonging care was initially chosen by 25 subjects. Of these subjects, 18 stated the belief that life should always be preserved, 3 cited the inherent good of medical treatment and 3 hoped for future cure. After the video of the 25 who initially chose life-prolonging care, 18 changed to comfort care and 6 changed to limited care. The rationale for changing preferences included: 8 desired relief of suffering; 6 cited the inherent good of medical treatment; and, 4 stated the quality of life in advanced dementia was not worth preserving. Limited care was initially chosen by 22 subjects. Of these subjects, 12 believed in the inherent good of medical treatment. Following the video, most changed to comfort care. Nine stated that the quality of life was not worth preserving and four prioritized the relief of suffering. Thirteen subjects were initially undecided and all chose comfort care after watching the video. The most common rationale for changing preferences was that the quality of life was not worth preserving. #### Conclusions Video may serve an important role in eliciting preferences and rationales for medical decision-making in dementia. These findings may help enhance advance care planning discussions ### 444 HOSPITAL READMISSIONS WITHIN 30 DAYS AFTER DISCHARGE: A REVIEW OF ALL READMISSIONS TO HOSPITALISTS IN ONE YEAR V. Jeevanantham, G. Jao, R. Vadlamudi, B. Gadi, M. Eapen, S. Stefanescu, P. Agborbesong *Wake Forest University, Winston Salem, NC*. #### Purpose of Study Centers for Medicaid and Medicare services are proposing to add hospital readmissions as a quality measure by the year 2010 due to the significant burden for patients and healthcare system. We aimed to study the characteristics of all readmissions within 30 days of discharge from hospitalist service in one year. #### Methods Used This was a retrospective study of all readmissions within 30 days after discharge from the hospitalist service during the year 2007. The review was done by seven physicians. Patients readmitted were identified from the University Health Consortium database. Factors for readmission were categorized as: patient factor (e.g. non compliance with treatment), physician factor (e.g. inadequate treatment), disease factor (e.g. end stage obstructive lung disease), and system issue (e.g. lack of primary care physician). #### Summary of Results The total number of readmissions in year 2007 was 239. Fifty five percent of all readmissions were men, 54.4% were Caucasians, 43.9% were African Americans and 1.7% were Hispanics. Seventy one percent of readmissions were for the same diagnosis as the original admission and 37.1% of readmissions were thought to be preventable. Fourteen percent of patients were discharged to skilled nursing facility while the majority of patients were discharged to home (59.8%) or home with home health services (13 %). A new medication was introduced in 15.9% of patients before discharge. The reasons for readmission were acute exacerbation of chronic illness (32.3%), medical non compliance (19.5%), new diagnosis or problem (18.2%), end stage illness (8.2%), failure of outpatient regimen (7.7%), substance abuse (6.4%), medication overdose or side effect (3.6%), and patient leaving against medical advice (2.7%). Patient factor caused 18.8% of readmissions, physician factor caused 2.9% of readmissions, disease factor caused 36.4% of readmissions, and a combination of more than one factor caused 33.8% of readmissions. #### Conclusions More than one third of our readmissions were thought to be preventable, however a combination of factors contribute to most readmissions. Interventions targeting multiple levels in the discharge process are necessary to reduce the readmission burden to our patients and health care system.