Biomedical subjects
T M Bayless
Publications and source records attributed to T M Bayless.
Increased HLA A1 and diminished HLA A3 in lymphocytic colitis compared to controls and patients with collagenous colitis.
Lymphocytic colitis is a newly described chronic diarrheal disorder. Although its etiology is unknown, the possibility has been raised that autoimmunity may play a role in both lymphocytic and collagenous colitis, a similar clinicopathologic illness. The frequencies of HLA class I and class II antigens were examined in 24 white patients with lymphocytic colitis and in 47 white patients with collagenous colitis. Frequencies in these two disorders were compared to control white populations and to each other. An increased frequency of HLA-A1 was noted in 16 of 24 lymphocytic colitis patients (66.6%) compared with 1089 of 3942 controls (27.6%) (P less than 0.005; relative risk 5.2). Furthermore, HLA-A3 was found in decreased frequency in lymphocytic colitis patients: 0 of 24 (0%) compared with 1017 of 3942 controls (25.8%) (P less than 0.05; relative risk 0.0). Collagenous colitis patients had no significant deviation from control frequencies of HLA antigens. In lymphocytic colitis, there was no significant increase in B8 or DR3 antigens, which are found in linkage disequilibrium with A1 and associated with many autoimmune diseases. Moreover, the frequency of autoimmune-associated class I HLA antigens was not increased in lymphocytic colitis. Statistically significant differences existed between lymphocytic and collagenous colitis in HLA-A1, A3, Bw6, and B7 antigen frequencies. The HLA patterns noted previously in other gastrointestinal disorders, including ulcerative colitis and Crohn's disease, were not apparent in lymphocytic or collagenous colitis. HLA typing provides further evidence that lymphocytic colitis is a distinct form of chronic intestinal inflammatory disease associated with HLA class I phenotypes.
Colonic short-chain fatty acids: fuel from the lumen?
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Increased interleukin-2 messenger RNA in the intestinal mucosal lesions of Crohn's disease but not ulcerative colitis.
Crohn's disease (CD) is characterized by granulomatous inflammation of the intestinal mucosa, but the etiology and pathogenesis of the inflammatory lesions are unknown. The aim of this study was to determine whether T-cell activation and lymphokine production occurs in the mucosal lesions of this disease. Total cellular RNA was isolated from peripheral blood lymphocytes and from colonoscopic mucosal biopsies of normal individuals and patients with CD of the colon or ulcerative colitis (UC). Levels of interleukin-2 (IL-2) messenger RNA (mRNA) transcripts in samples were determined using a quantitative reverse transcriptase polymerase chain reaction method. IL-2 mRNA transcripts were detected in histologically normal intestinal mucosal biopsies obtained from control subjects. In CD, higher levels of IL-2 mRNA transcripts were detected in the mucosa from areas of active inflammation, but in areas that were histologically normal, levels were similar to control subjects. The levels of IL-2 mRNA transcripts in biopsies from active and inactive UC were similar to control subjects. Levels of IL-2 mRNA in peripheral blood lymphocytes were low and not significantly different in all groups of subjects. In conclusion, the normal intestinal mucosa contains IL-2 mRNA transcripts and may be an important source of IL-2. Furthermore, the inflammatory lesions of CD, but not UC, have higher levels of IL-2 mRNA transcripts, suggesting that T-cell activation and lymphokine secretion in the intestine may be important in the pathogenesis of CD. These data provide further evidence that the pathogenesis of CD and UC are different.
Patterns of ileal recurrence in Crohn's disease. A prospective randomized study.
To gain information on the pathogenesis of ileal recurrence, 86 patients with Crohn's disease undergoing their first ileocolic resection were randomized to receive either an end-to-end (n = 47) or side-to-end (n = 39) anastomosis. The demographic and clinical characteristics of both groups were similar. There were no statistically significant differences between the two groups in postoperative complications or in the subsequent development of symptomatic or documented recurrences. Among the 43 patients with follow-up in the end-to-end anastomosis group, there were 10 documented ileal recurrences (23%), and all involved distal ileum in the characteristic preanastomotic location. Among the 35 patients with follow-up in the side-to-end anastomosis group, there were 11 documented recurrences (31%, not significant). The ileal recurrence pattern could be determined accurately in five of these 11 patients and involved the ileum adjacent to the colon, but spared the distal ileum in the blind pouch. This study suggests that the fecal stream and reflux of colonic contents are important factors in determining the pattern of ileal recurrence after ileocolectomy for Crohn's disease.
Breath hydrogen testing as a physiology laboratory exercise for medical students.
Breath hydrogen testing (BHT) is a simple and reliable method for identifying impaired carbohydrate absorption. We describe a laboratory exercise in physiology for medical students using BHT as the teaching tool. The students collect fasting samples of expired air from each other using a simple nasal prong technique. They then drink one of several different aqueous carbohydrate solutions. Additional samples of expired air are collected by the students at 90 and 120 min after substrate ingestion and are analyzed by gas chromatography. Between sampling periods, discussions of digestive physiology are provided by the faculty. Students tabulate their BHT results as well as recording any symptoms using a standard scoring system. A total of 460 students have participated. We found that the percentage of students who malabsorbed a given substrate was similar each year. The results obtained in these student exercises closely parallel those reported in the literature. We conclude that BHT is an excellent teaching tool for illustrating carbohydrate digestion and absorption, even when performed by minimally trained subjects.
Hyperplasia of Brunner glands: the spectrum of its radiographic manifestations.
Radiographic features of the duodenal mucosa were analyzed in a series of 26 patients in whom the diagnosis of Brunner gland hyperplasis (BGH) had been established by endoscopic biopsies. The observed mucosal patterns could be classified into five categories: (1) focal BGH causing a solitary submucosal adenoma or a cluster of sessile polyps in the otherwise smooth duodenal bulb surface (five cases); (2) diffuse BGH manifested by a myriad of small and uniform mucosal elevations (six cases); (3) multifocal BGH producing large and well-demarcated polygonal masses (six cases); (4) BGH with concomitant acute and/or chronic duodenitis showing marked thickening and nodularity of duodenal folds (four cases); or (5) BGH with predominant erosive duodenitis, leading to ulcerations (five cases). These radiographic findings showed a good correlation with the endoscopic and histopathologic manifestations of BGH and the frequently coexistent duodenitis.
Use of azathioprine or 6-mercaptopurine in the treatment of Crohn's disease.
The efficacy and safety of therapy with azathioprine/6-mercaptopurine was studied in 78 patients with Crohn's disease. Mean duration of therapy was 1.6 years; 52 patients were treated greater than or equal to 6 months. All patients were also on other antiinflammatory medications. Evaluations included self-assessment and physician's assessment of well-being, functional capacity, general clinical response, clinical activities indices (National Foundation for Ileitis and Colitis/International Organization for the Study of Inflammatory Bowel Disease and Harvey-Bradshaw), and achievement of specific therapeutic goals. General clinical condition improved in 70% of the patients. Median response time was 3 months. The average Harvey-Bradshaw score decreased 37% with therapy, and a decrease of greater than or equal to 30% occurred in 66% of the subjects. An overall 72% achievement rate for specified therapeutic goals included controlling refractory disease, 73%; corticosteroid "sparing," 76%; and lessening fistulization, 63%. Nine patients got worse despite therapy. Adverse effects requiring discontinuation of therapy occurred in 10%, whereas dosages were briefly lowered for mild side effects in another 10%. This study demonstrates the effectiveness and safety of azathioprine/6-mercaptopurine in the majority of selected patients with chronic, unremitting, or steroid-requiring Crohn's disease.
Undergraduate teaching project of the American gastroenterological Association: a pathophysiology resource.
The Undergraduate Teaching Project was founded as a committee of the American Gastroenterological Association to improve medical school teaching of the pathophysiological basis of gastrointestinal and liver diseases. Twenty-six units of colored illustrations have been produced in 18 years, which are designed to be used by instructors to supplement their own material. The slides are the result of extensive reviews and revisions, a process that has created a unique repository of educational concepts utilized by most US medical schools and over 50 foreign schools. This brief summary of the genesis and operation of this venture may be of interest to other professional societies concerned with the development of teaching materials.
Favorable response to parenteral nutrition and medical therapy in Crohn's colitis. A report of 38 patients comparing severe Crohn's and ulcerative colitis.
The courses of 38 patients with severe, uncomplicated acute colitis (16 with Crohn's colitis and 22 with ulcerative colitis) were analyzed retrospectively. The patients were placed on total parenteral nutrition and treated concomitantly with corticosteroids, antibiotics (often metronidazole), sulfasalazine, and/or azathioprine. Fifteen of the 16 Crohn's colitis patients were initially managed without surgery. Four patients subsequently relapsed, two responded to reinstituted medical therapy, and two underwent colon resection 2 and 4 years later. Of 22 ulcerative colitis patients, 16 required surgery during the initial hospitalization, one patient subsequently had surgery, and one died after refusing surgery. Three of the other four continue in remission on medical therapy. Thus, there were significant differences in this series between the clinical courses of severe ulcerative colitis and severe Crohn's colitis. While most of the ulcerative colitis patients with severe disease underwent colectomy, most of the patients with severe but uncomplicated Crohn's colitis responded to aggressive medical therapy, of which total parenteral nutrition and perhaps bowel rest seemed to be an important part. Afterwards, the majority remained in remission on long-term medical therapy.
Enhancement of human intestinal mast cell mediator release in active ulcerative colitis.
To further define the role of mast cells in the idiopathic inflammatory bowel diseases, mediator release from intestinal mast cells derived from actively inflamed and relatively quiescent areas of ulcerative colitis was studied. It was hypothesized that mast cells in the actively diseased segments would indicate involvement in the disease process by releasing a different profile of mediators than cells in uninflammed tissue. Mast cell-containing suspensions derived from matched segments of 12 ulcerative colitis specimens were compared for responsiveness to the mast cell stimulus goat anti-human immunoglobulin E. Supernatants from challenged cells were analyzed for levels of three mast cell mediators, histamine, prostaglandin D2, and the sulfidopeptide leukotriene C. Mast cells from the actively involved areas released significantly greater amounts of histamine, prostaglandin D2, and sulfidopeptide leukotriene. The difference in histamine release was not a result of greater stores of histamine in the active tissue cells, because the total histamine content of the mast cells from the active areas was not significantly greater. The enhanced release of both preformed and newly generated mediators indicates activation of those cells in the course of the disease and points to the mast cell contribution to the inflammatory process in these disorders.
Whipple's disease: a multisystem infection.
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Postcholecystectomy diarrhea.
Diarrhea developed in three patients following cholecystectomy. Fecal bile-acid excretion was elevated in the two patients for whom it was measured. All three patients' diarrhea resolved with cholestyramine resin therapy. This experience suggests that gallbladder removal may lead to a bile-acid-mediated diarrhea in some patients, and that this condition appears to respond to cholestyramine therapy.
Malabsorption in the elderly.
Age-related deficiencies in gastrointestinal function do occur, but the evidence suggests that their contribution to malabsorption syndromes is usually trivial. Symptoms of malabsorption in elderly patients therefore probably do not simply reflect "old age," but some underlying problem(s). An orderly approach to diagnosis, emphasizing disorders likely to be present in the geriatric population, can lead to effective treatment.
Hormone-mediated watery diarrhea in a family with multiple endocrine neoplasms.
A father and son each presented with severe watery diarrhea. The son was found to have a pancreatic islet-cell tumor associated with the pancreatic cholera syndrome, as well as a parathyroid adenoma. The father was found to have multiple islet-cell adenomas and the Zollinger-Ellison syndrome. Pancreatic tumor tissue from each patient contained detectable gastrin and vasoactive intestinal peptide; however, a much higher gastrin concentration was found in the tumor tissue from the father and a much higher vasoactive intestinal peptide content in the tumor tissue from the son. Thus, watery diarrhea may be mediated by different hormones in families having multiple endocrine neoplasia; the precise cause of the diarrheal syndrome should be defined to ensure the proper therapy.
Cancer in ulcerative colitis.
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