$1063

Failure of Mesalamine to Resolve the Diarrhea of Microscopic Colitis Suggests a Comorbid Illness Charles W. Randall, Carlo M. Taboada, Jennifer Kimble

Background: Several published reports have shown mesalamine to be efficacious in the treatment of Microscopic Colitis (MC) that includes Lymphocytic Cohtis (LC) and Collage- nons Colitis (CC). This study examined the possibility that patients with MC who did not respond to mesalamine may have co-existing diarrheal illnesses. Methods: 53 patients diagnosed with Microscopic Colitis by histological examination were treated with 2.4 gr. of mesalamine (Asacol) per day. Remission was defined as complete resolution of diarrhea. All non-responders and 18 responders underwent follow-up colonic biopsy. A careful history and exam was performed on all patients. Results: Of the 18 responders to mesalamine, only 1 patient had persistent evidence of MC on histological examination. In the non-responder group, 2 patients had persistent histological evidence of microscopic colitis while the remain- ing 19 showed histological remission. Further evaluation of these 19 patients found 16 patients with [BS, 1 patient with lactose intolerance and 2 with both IBS and lactose intolerance. None of the responders had symptoms other than diarrhea nor any pertinent exam findings. 19 of the non-responders had histories of bloating, increased intestinal gas, cramping, abdominal pain or distension. 11 of the 18 IBS patients had mild diffuse abdominal tenderness on exam. Conclusions: 1.Patients with MC who fail mesalamine therapy require evaluation for other disorders. 2.Repeat colonic biopsy and histological examination is helpful in distinguishing persistent MC from other causes of diarrhea. 3.Painless diarrhea with a paucity of exam findings distinguishes MC from [BS and/or lactose intolerance.

$1064

Pedialyte Or Gatorade For Viral Gastroenteri t is In Adults: Controlled Clinical Trial Sadsh Rao, Rw Summers, C. Gisolfi, Grs Rao, S. Ramana, U. Devi, B. Zimmerman, D. Rotella, B. Pratap

Pedialyte (P) and Gatorade(G) are frequently advocated for the treatment of dehydration in acute viral gastroenteritis, but they have not been compared and there is limited evidence to support their use. We performed a randomized double blind trial to examine and compare the efficacy, safety, palatability and clinical utility of these solutions. Also, we tested the efficacy of a new solution (NS) that contained 4% carbohydrate, 35 mEq/L sodium and 25 mEq/L potassium. Methods: 75 patients (m/f=44/33) admitted with viral gastroenteritis were randomized to receive G, P or N S for 48 hours. A yogurt/rice diet was allowed ad libitum. Stool & urine output, electrolytes, fluid retake, body weight & hematocrit were assessed at admission and on each day. Stools were cultured & examined for O & P. Patient satisfaction and palatability were rated on a VAS. Data analyst & Statistician were blinded. Results: 60 patients completed the study. Data in table shows mean or median (#) values. * = p<0.05 vs admission; # = p<0.05 vs Pedialyte. Stool frequency, consistency and body weight improved in all 3 groups and there was no difference. There were no differences in urine output, hematocrit and correlations between volume of fluid ingested and stool weight or urine output. Conclusions: Gatorade appears to be as effective as Pedialyte in correcting dehydration and in improving bowel symptoms. All 3 solutions were safe. Hypokalemia persisited in the Gatorade group, unlike the other two groups. Taste wise, G & NS were rated higher than P. Gatorade may be useful in treating dehydration associated with mild viral gastroenteritis, but a more balanced electrolyte solution such as NS that was equally tasty may be more efficacious. Supported by a grant from The Gatorade Sports Science Institute.

Oatoradef n=22 New Solution~ a=t9 Pedlalyte r n,,19 Admit 24h 48h Admit 2,4h 48h Adst~ 24h 48h

BadyWt (Kg) 45.3 46,7 47.2 51.8 53.5 54 51.6 52.6 53 S,Frequency. 10.4 4,5' 3.2' 10,1 4,9* 3.2" 8.4 4.7' 3.1'

%stool ua- 100 89 11" 96 94 28* 100 89 17" fumled Tut~VAS 8,3# 8.1# 5.4

Vol.lngnted 4000 3000 4000 3000 4000 3000

Stool Wt (9) 592 430* 581 497* 570 463* Hypekaklmla 7 10 8 3 2 1 2 2 1 Hpoutrwnla 8 9 3 5 3 4 4 5 4

S1065

HlV-Associated Diarrhea in the Era of HAART: Still Prevalent After All These Years Uzma Siddiqui, Edmund J. Bini, Khushbu Chandarana, Sabena Ramsetty, Michael A. Poles

Background: Prior to the introduction of highly active antiretroviral therapy (HAART) in i995, H1V-associated diarrhea was highly prevalent. Although anecdotal evidence suggests that HAART has decreased the incidence, morbidity, and mortality of HIV-associated diarrhea, this has not been evaluated in prospective studies. The aims of this study were to determine the prevalence of diarrhea in HIV+ patients in the HAART era and to evaluate the impact of diarrhea on health-related quality of life (HRQOL). Methods: Consecutive H1V + patients seen in infectious disease clinics at two medical centers were enrolled in this study. HIV seronegative patients recruited from primary care clinics served as healthy controls. Diarrhea symptoms were evaluated using a validated questionnaire and HRQOL was assessed using the SF-36 survey. Results: Baseline characteristics did not differ significantly between the 116 HIV+ patients and the 134 healthy controls. In the HIV+ group, the median CD4 count was 342 cells/mm 3 and the median viral load was 155 copies/mL. HIV+ patients reported having diarrhea within the past month sigmficantly more than healthy controls (38.3% vs 19.4%, P<O.001). A greater proportion of HIV+ patients reported having 3 or more bowel movements per day within the past 7 days (26.1% vs 5.2%, P<O.001) and within the last 6 months (27.4% vs 6.0%, P<0.001) when compared to controls. More HIV+ patients described their stool consistency as either loose or liquid within the past

month when compared to healthy controls (19.1% vs 7.4%, P = 0.001). HRQOL scores in HIV+ patients with diarrhea within the past month were significantly lower than in healthy controls for physical functioning (73 vs 84, P = 0.017), role-physical (42 vs 66, P = 0.003), general health (54 vs 67, P = 0.003), vitality (47 vs 60, P = 0.006), social functioning (72 vs 85, P = 0.006), and role-emotional (57 vs 81, P = 0.001). Use of antidiarrheal medications was greater among HIV + subjects than among healthy controls (14.8% vs 0.7%, P<0.001). Conclusions: Diarrhea remains an important problem and significantly impairs HRQOL in HIV+ patients in the HAART era. It is important that healthcare providers specifically evaluate their HIV+ patients for diarrhea so that these symptoms may be optimally managed.

S1066

Lactulose/Mannitol Test Has High Efficacy for Identifying Organic Causes of Chronic Diarrhea Vincenza Di Leo, Renata D'Inca', Natalia Diaz-Granado, Walter Fries, Carla Venturi, Anna D'Odorico, Diego Martines, Giacomo C. Stumiolo

Diagnosis in chronic diarrhea m the absence of a distinctive clinical pattern is often challeng- ing, as biochemical tests, prescribed at the first evaluation, do not show enough sensitivity and specificity to tailor further investigation. Intestinal permeability to sugars is an accurate test for detecting intestinal damage. We conducted a prospective cohort study to evaluate the diagnostic value of lactulose/marmitol (L/M) test in chronic diarrhea. The test was administered to 261 consecutive patients presenting with three or more bowel movements per day for at least two weeks. Biochemical tests including complete blood cell count, acute phase reactive proteins, serum albumin and iron, stool cultures for bacteria, ova and parasites were assessed at the same time. Additional diagnostic investigations were directed by clinical features, as well as first line tests results. Over three years, 120 (46%) of our patients were found to have an organic cause for chronic diarrhea, whereas in 141 (54%) a functional condition was diagnosed. Multivariate logistic regression analysis, revealed that the UM test and C-reactive protein were independent predictors for the final diagnosis of organic cause of chronic diarrhea, with odds ratios (adjusted for age) of 1.5 (95% C.I. 1.29 to 1.78) and 5.2 (95% C.I. 1.90-14.12) respectively. The area under the receiver operating characteristic curve (ROC curve) of the adjusted model was 0.82. In conclusion, UM is a powerful tool for the work up of patients with chronic diarrhea. Introducing UM test as first level test effectively improves the selection of patients who need further evaluation.

S1067

Postischemic Anti-Inflammatory Effects of Ethanol Preconditioning (EPC) Are Initiated by Adenylyl Cyclase/Protein Kinase A Activation Kazuhiro Kamada, Taiji Yamaguchi, Toshikazu Yoshikawa, Ronald J. Korthuis

[Background] Ethanol consumption (EPC) at a dose equivalent to ingesting one alcoholic beverage 24 hrs prior to ischemia/reperfnsion (I/R) prevents postischemic leukocyte-endothe- lial cell adhesive interactions (LEI) by a mechanism that is triggered by the activation of adenosine A2 receptors during the period of ethanol exposure. The aim of this study was to determine the roles of adenylyl cyclase and protein kinase A as downstream signaling elements that produce the anti-inflammatory effects of EPC in I/R [Methods] Ethanol was administered to C57BL/6 mice by garage (peak plasma levels of 45 mg/dl 30 min after ingestion). 24 hrs later, the superior mesenteric artery was occluded for 45 rain followed by 60 min reperfnsion. The numbers of fluorescently-labeled rolling (LR,/mm2/min) and adherent (LA,/mm 2) leukocytes in postcapillary venules of the small intestine were quantified using intravital microscopy after 60 rain of reperfusion. Mice were treated with either adenylyl cyclase (SQ22536, 100p,M, or MDL12330A, 250p.M) or protein kinase A(KT5720, lp,M, or Rp-8-Br-cAMP, 4001zM) inhibitors by ip injection 10 min prior to ethanol ingestion followed by 3 cycles of peritoneal lavage 70 min later on Day 1. Other mice were precondi- tioned with agents that increase intracellular cAMP (dibutyryl cAMP, 25 mg/kg, forskolin, 101zM, or isoproterenol, lp, M, ip) for one hour on Day 1, in lieu of ethanol. I/R was induced on Day 2 in all experiments (except time control shams). [Results] I/R induced marked increases in LEI (LR, LA: 100%, 100%) as compared with sham (24.1%, 26.7%). Postischemic LEI were prevented by EPC (31.4%, 45.6%). The effects of EPC to reduce postischemic LA, but not LR, were attenuated by coincident adenylyl cyclase (SQ22536: 36.5%, 83.4% and MDL12330A: 39.2%, 81.6%) or protein kinase A (KT5720: 47.0%, 66.6% and Rp-8-Br- cAMP: 36.4%, 60.7%) inhibition during EPC. On the other hand, preconditioning with dibutyryl cAMP (51.2%, 67.0%), forskolin (39.5%, 31.1%) or isoproterenol (39.3%, 40.3%) mimicked the protective effects of EPC and prevented postischemic LE[. [Conclusions] These findings indicate that the effects of EPC to reduce postischemic LA are initiated by an adenylyl cyclase/protein kinase A-dependent mechanism. Supported by NIH grants HL 54797 and DK 43785.

s1068

PPI Protect Against Anoxia-lnduced Apoptosis In Endothelial Cells Kazuhiro Katada, Norimasa Yoshida, Naoyuki Matsumoto, Hiroki Manabe, Makoto Shimozawa, Eiko lmamoto, Kazuhiko Uchiyama, Tomohisa Takagi, Taiji Yamagnchi, Satoshi Kokura, Hiroshi Ichikawa, Yuji Naito, Toshikazu Yoshikawa

Background: Recently, it has been suggested that proton pump inhibitors (PPI) have the anti-inflammatory actions such as the antt-neutrophdic function and the inhibition of both IL-8 production and adhesion molecule expression.These actions beyond the acid suppression may play an important role in protection against cell damage. In the present study, we investigated whether PPI have the protective effects on vascular endothelial cell injury during anoxia and reoxygenation. Methods: Confluent human aortic endothelial cells (HAEC) monolayers were exposed to anoxia by incubation in a Plexiglas chamber that was continu- ously purged with an anoxic gas mixture (95% nitrogen and 5% carbon dioxide). After a period of anoxia, reoxygenation was initiated by exposing the endothelial cells to room air. In control experiments, HAEC were identically treated except that they were exposed to

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