Pouchitis in ulcerative colitis: correlation between predictors from colectomy specimens and clinico-histological features.

Pouchitis after restorative proctocolectomy for ulcerative colitis is usually of ill-defined etiology and is encountered with sclerosing cholangitis, bacterial overgrowth, and ischemia. Recently, appendiceal involvement, ileitis, and fissures in the colectomy specimen have been associated with short- and long-term development of pouchitis. To corroborate these recent findings, the histology of 40 colectomies (70% males; mean age 46.3 years, age range 20-70 years; mean follow-up period 3.7 years, range 1-13 years) with yearly follow-up biopsies was correlated with pouchitis and clinical symptoms. Appendicitis, fissures, and ileitis were present in 47, 45 and 5% of the patients, respectively. Pouchitis in patients with appendicitis or with fissures was noted in 44 and 50% at first biopsy and in 70 and 58% during follow-up (p = NS). Of the patients without appendicitis or without fissures, 33 and 33% demonstrated pouchitis at the first biopsy and 30 and 55% during follow-up (p = NS). Clinico-histological correlation revealed normal/near-normal biopsies with the lowest clinical severity score in 77% and with the highest clinical score in 43% (p < 0.025). The histological findings of appendiceal involvement, fissuring ulcers, and ileitis in colectomies for ulcerative colitis do not correlate with the finding of pouchitis in early or late pouch biopsies. A high clinical suspicion score is frequently not correlated with significant inflammation of the pouch.

Inflammatory bowel disease is not associated with an increased risk of lymphoma.

BACKGROUND & AIMS: Previous studies of the risk of lymphoma in inflammatory bowel disease patients have provided conflicting results. This study examines the risk of Hodgkin's and non-Hodgkin's lymphoma among patients with inflammatory bowel disease. METHODS: The authors performed a retrospective cohort study using the General Practice Research Database. Inflammatory bowel disease patients were matched to randomly selected controls on age, sex, and primary care practice. Lymphoma rates were also compared with published age- and sex-specific rates. RESULTS: The study included 6605 patients with Crohn's disease, 10,391 with ulcerative colitis, and 60,506 controls followed for an average of 3.7, 3.9, and 4.4 years, respectively. The incidence of lymphoma was not increased in patients with inflammatory bowel disease (relative risk = 1.20; 95% CI, 0.67-2.06). In subgroup analyses, an increased risk was not observed among patients with Crohn's disease (relative risk = 1.39; 95% CI, 0.50-3.40) or ulcerative colitis (relative risk = 1.11; 95% CI, 0.51-2.19). Compared with inflammatory bowel disease patients not treated with azathioprine or 6-MP, the relative risk of lymphoma among the 1465 inflammatory bowel disease patients treated with these medications (average, 106 mg/day for 2.0 years) was 1.27 (95% CI 0.03-8.20). CONCLUSIONS: Patients with inflammatory bowel disease do not have an increased risk of lymphoma as compared with the general population. Although we cannot completely rule out a modest increased risk of lymphoma with azathioprine or 6-MP therapy, an increased risk was not observed in this cohort.

An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis.

OBJECTIVES: Previous research has demonstrated that ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARs) reduce inflammation in two different murine models of colitis. This study was designed to examine the potential efficacy of rosiglitazone, a ligand for the gamma subtype of PPARs, as a therapy for active ulcerative colitis. METHODS: Fifteen patients with mild to moderately active ulcerative colitis despite therapy with 5-aminosalicylic acid compounds were enrolled in an open-label study of rosiglitazone (4 mg b.i.d. p.o.) for 12 wk. Thirteen of 15 patients were receiving concomitant therapy with corticosteroids and/or immunomodulator medications. Disease activity was measured with the Disease Activity Index. RESULTS: After 12 wk of therapy, four patients (27%) had achieved clinical remission, of whom three (20%) also had an endoscopic remission. Four additional patients (27%) had a clinical response without achieving remission. Two patients were hospitalized with worsened disease activity, and one patient was withdrawn for nephrotic syndrome. CONCLUSIONS: These data suggest that ligands for the gamma subtype of PPARs may represent a novel therapy for ulcerative colitis. A double blind, placebo-controlled, randomized trial is warranted.

Distinction between dysplasia-associated lesion or mass (DALM) and adenoma in patients with ulcerative colitis.

Polyps with epithelial dysplasia in ulcerative colitis (UC) represent either dysplasia-associated lesions or masses (DALMs) or sporadic adenomas. DALMs are frequently associated with associated carcinoma and are an indication for colectomy. Removal of the polyp is treatment of choice for sporadic adenomas. Differentiating between these 2 lesions is not always easy. The goal of this study was to distinguish DALMs from adenomas in patients with UC on a genetic basis. We evaluated genetic alterations in DALMs and compared them with a previously published set of dysplastic polyps in patients with UC that were considered adenomas for the following reasons: (1) polyps were located outside of current active disease; (2) polyps had histological features of sporadic adenomas; and (3) patients displayed a uneventful follow-up after polypectomy (UC-adenomas). In addition, adenomas not associated with UC were studied. Genetic alterations on chromosome 3p were assessed for the markers D3S1766, D3S2409, and D3S2387. LOH with or without microsatellite instability was found in 70%, 37%, and 57% of cases of DALM, respectively. In contrast, UC-adenomas lesions exhibited genetic alterations in 8.3%, 11.7%, and 15.3% for the respective markers. Spontaneous adenomas exhibited genetic alterations in 10.5%, 7.1%, and 0% of cases, which were not significantly different from the UC-adenoma results. These results indicate that UC-adenomas are genetically and biologically similar to sporadic adenomas and that UC-adenomas may biologically represent sporadic adenomas, supporting on a genetic basis the criteria chosen to diagnose adenomas in UC. Genetic markers on chromosome 3p may be useful in the differential diagnosis between DALM and UC-adenomas.

Cancer risk in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk for developing cancer of the gastrointestinal tract, particularly colorectal cancer. Because of the relative rarity of IBD in the general population, it has been difficult to quantify this risk. Efforts to reduce the risk have included both prophylactic surgery and endoscopic screening programs. Because of the potential impact on quality of life and life expectancy, the optimal strategy for reducing this risk has not been defined. This article reviews the current literature relating to the risk of cancer for patients with IBD and methods to reduce this risk.

A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis.

OBJECTIVES: The aim of this study was to compare the efficacy of mesalamine rectal suspension enema (Rowasa) alone, oral mesalamine tablets (Asacol) alone, and the combination of mesalamine enema and mesalamine tablets in patients with active mild-to-moderate distal ulcerative colitis. METHODS: Sixty outpatients with ulcerative colitis at least 5 cm above the anal verge and not more than 50 cm, inclusive, and a total disease activity index (DAI) score between 4 and 10, inclusive, were randomized to either mesalamine rectal enema (n = 18) once nightly, oral mesalamine 2.4 g/day (n = 22), or a combination of both treatments (n = 20). Placebo capsules and enemas were used to maintain a blind procedure. Total DAI scores and abbreviated DAI scores were evaluated at wk 3 and 6, and wk 1 and 2, respectively. Patients recorded the amount of blood in stools, urgency, straining at stools, and abdominal pain in daily diaries. Physicians and patients rated overall improvement at each visit. RESULTS: At wk 6, combination therapy produced a greater improvement (-5.2) in total DAI scores than did either mesalamine enema (-4.4) or mesalamine tablet (-3.9) therapy alone; similar treatment differences were observed at wk 3. Compared with patients given mesalamine enemas or mesalamine tablets, combination-therapy patients reported an absence of blood in stools significantly sooner and, at all visits, the combination therapy group had the highest percentage of patients who reported no blood in their stools. Physicians' and patients' ratings of improvement indicated that combination therapy significantly improved disease status, compared with mesalamine tablet therapy alone. All treatments were well tolerated. CONCLUSIONS: The combination of oral and rectal mesalamine therapy was well tolerated and produced earlier and more complete relief of rectal bleeding than oral or rectal therapy alone.

Production of chemoattractant by Helicobacter pylori.

Helicobacter pylori is present in the antral region of the stomach in a majority of patients with gastritis type B. The specific mechanism whereby the organism participates in the development of disease remains uncertain. Since the organism is not invasive, we postulate that H. pylori produces a chemoattractant that recruits inflammatory cells to the antral region of the stomach. H. pylori was grown under microaerophilic conditions at 37 degrees C for 72 hr in Brucella broth containing 1% fetal bovine serum. Culture supernates were harvested after removal of organisms by centrifugation and filtration. The putative chemoattractant in culture supernates as well as that which might be present endogenously in the growth medium (negative control) was assayed against human neutrophils (PMN) in modified Boyden blind-well chambers using 3.0-microns membranes. We found that H. pylori supernates are chemotactic and showed up to 130% activity when compared to the positive chemoattractant control (zymosan-activated serum, a source of C5a). Minimal activity was observed with virgin growth medium. The chemoattractant activity is proportional to the number of colony forming units (CFU) of H. pylori. Preliminary characterization of the activity shows that the chemoattractant is stable in a boiling water bath for 15 min, activity is lost within 1 hr in acid or alkali, and the chemotactic factor has an approximate molecular weight of 8500 daltons. The factor has no amino-sugar and is negative for the lipid A portion of lipopolysaccharide.(ABSTRACT TRUNCATED AT 250 WORDS)

Shoulder after surgery: MR imaging with surgical validation.

To assess the accuracy of magnetic resonance (MR) imaging in the evaluation of the shoulder after surgery, MR examinations were performed in 31 patients before repeated surgery, and MR findings were correlated with the subsequent operative findings. In addition, the MR findings associated with prior surgery were reviewed, including altered structure of the acromion, soft-tissue metal artifacts, a surgical trough in the humeral head, nonvisualization of the subacromial-subdeltoid fat stripe, and intermediate signal intensity within the substance of the rotator cuff on images obtained with all pulse sequences. The MR criteria for full-thickness tears in the shoulder after surgery are the presence of fluidlike signal intensity on T2-weighted images that extends through an area of the rotator cuff or the nonvisualization of a portion of the rotator cuff. With use of these criteria, six of seven full-thickness rotator cuff tears were identified at MR imaging, with an accuracy of 90%. Partial cuff tears were indistinguishable from repaired tendons. Findings at MR imaging were 74% accurate concerning the presence of impingement.

Alkaline phosphatase production by periosteal cells at various oxygen tensions in vitro.

A mammalian periosteal cell culture system was developed to investigate the metabolic response of fresh calf bone periosteal cells to various oxygen tensions in vitro. Two predominant cell phenotypes were seen in the culture system. A rapidly proliferating mat of alkaline phosphatase-negative cells supported the growth of overlying clusters of alkaline phosphatase-positive cells. The appearance and subsequent population growth of the alkaline phosphatase-positive cells correlated directly with increases in enzyme activity on biochemical assay. Alkaline phosphatase production was optimal at lower oxygen tensions (5%, 9%), which approximated capillary pO2. In addition, the preconfluence oxygen environment was more critical to the final expression of the enzyme activity than the postconfluence environment. The mechanism of the environmental regulation of alkaline phosphatase gene expression at various oxygen tensions is not known. Periosteal cells were highly sensitive to oxygen tension and expressed alkaline phosphatase enzyme activity at oxygen levels approximating capillary rather than atmospheric pO2.

Mucinous cystadenoma: pitfalls of differential diagnosis.

Cystic neoplasms of the pancreas often are difficult to differentiate from pseudocysts. It has been proposed that a history of clinical pancreatitis, elevated serum pancreatic enzymes, elevated cyst fluid amylase, and a communication with the pancreatic duct suggest the diagnosis of a pseudocyst. We report the case of a young woman who presented with a cystic mass in the pancreas and was thought to have a pseudocyst because of the above; at surgery, a mucinous cystadenoma was documented. The pitfalls of differentiating neoplastic cysts of the pancreas from pseudocysts are discussed.

Limited weight losses with a gastric balloon.

An evaluation of the Garren-Edwards gastric bubble in the treatment of obesity was done. Several clinical trials have compared the effects of behavior therapy with and without the bubble, but the effects of the bubble alone have not been previously evaluated. Ten obese women averaging 91% overweight received the bubble without adjunctive therapy during a 12-week treatment period. Frequent psychological and laboratory measures as well as weight were obtained during the study to explore the possible mechanisms of the bubble's effect and its side effects. Mean weight change was -2.5 kg, with a range of -8.8 to +1.6 kg. Four patients lost more than 3.5 kg, three lost less than 3.5 kg, and three gained weight. The Garren-Edwards gastric bubble alone does not appear to provide significant benefit to most obese patients.

Alpha 1-antitrypsin levels predict mortality from ethionine-induced pancreatitis in mice.

Experimental pancreatitis can be induced by an ethionine-containing, choline-deficient diet in mice. We investigated the role of circulating alpha 1-antitrypsin in this model using two strains of mice: ICR and C57BL-6. A 50% reduction in circulating alpha 1-antitrypsin occurred in all mice by day three of diet exposure. Total protein was reduced by only 9% and albumin was unchanged. Female mice of both strains had significantly lower alpha 1-antitrypsin levels than male mice prior to and after diet exposure. This was associated with significantly greater mortality in both female strains. Interstrain comparisons showed a significantly higher mortality in the C57BL-6 females (100%) compared to the ICR females (58%); this corresponded to significantly lower alpha 1-antitrypsin levels in C57BL-6 females. Regardless of sex or strain, alpha 1-antitrypsin levels prior to and after diet exposure were significantly higher in mice surviving than in mice dying. We conclude that circulating alpha 1-antitrypsin is a predictor of mortality from diet-induced pancreatitis.

A multicenter placebo-controlled clinical trial of oral metoclopramide in diabetic gastroparesis.

Metoclopramide tablets were compared with placebo in the treatment of gastrointestinal symptoms in 40 patients with diabetic gastroparesis. Results of a 3-wk double-blind study indicate that metoclopramide at a dosage of one 10-mg tablet four times daily reduced nausea, vomiting, fullness, and early satiety and improved meal tolerance better than placebo. Statistically significant differences were noted for nausea and postprandial fullness. Mean gastric emptying assessed by radionuclide scintigraphy was significantly improved in the metoclopramide-treated group when compared with their baseline result. Metoclopramide is an effective agent for improving the upper gastrointestinal motor function in diabetic patients with gastroparesis.

Characteristics of intestinal glucose secretion in normal and diabetic rats.

A method was developed to characterize and quantitate the transfer of glucose from the plasma to the intestinal lumen. In normal rats, there was a linear correlation between the blood glucose concentration and the rate of appearance of plasma glucose into the intestinal lumen perfused with Krebs-Ringer buffer (r = 0.88, P less than 0.01). Intestinal perfusion with buffers containing either mannitol, glucose, or phlorizin significantly increased the recovery of secreted glucose compared with plain buffer. Rats perfused with buffer containing mannitol or those undergoing plasma volume expansion with dextran demonstrated a change in water movement from net absorption to secretion coupled with a significant increase in glucose secretion. During luminal perfusion with a buffer containing 21 mM glucose, glucose secretion represented 14% of the net glucose absorption rate. Intestinal perfusion with phlorizin gave the highest measured recovery of glucose, probably by blocking active reabsorption of secreted glucose. A series of simultaneous perfusions performed in the jejunum and ileum revealed similar rates of glucose transfer in both segments of intestine. Measurement of glucose secretion in rats with streptozotocin diabetes gave the highest values for the plasma-to-lumen movement of glucose. Treatment with insulin reduced the blood sugar and glucose transfer rate. These data demonstrate that glucose moves bidirectionally across the rat intestine, and its secretion is a passive process.

Azathioprine-related pancreatitis in patients with Crohn's disease.

Pancreatitis developed in 6 patients in the National Cooperative Crohn's Disease Study. In five of these the diagnosis was confirmed by elevated levels of seum amylase or lipase. All cases were in the 113 patients who received azathioprine and occurred within the first 21 days of treatment. This incidence of pancreatitis was significantly greater than in the patients treated with sulfasalazine, prednisone, or placebo (P less than 0.01).