Martin H. Ulshen

Pathogenesis of escherichia coli gastroenteritis in man--another mechanism.

ESCHERICHIA COLI infection of the gastrointestinal tract may cause diarrhea by two pathogenic mechanisms that have been well described in laboratory animals and man: direct invasion of the intestin...

Enhanced growth of small bowel in transgenic mice overexpressing bovine growth hormone

BACKGROUND Transgenic mice with a bovine growth hormone gene linked to a mouse metallothionein I promoter (growth hormone transgenics) are a model of chronic growth hormone excess. METHODS Growth of small bowel mucosa in ad libitum-fed growth hormone transgenics and wild type littermates and in growth hormone transgenics pair fed with wild-type littermates were compared. RESULTS In both groups, body weight and small bowel weight were greater in growth hormone transgenics. Similarly, mucosal mass was 50%-100% greater in growth hormone transgenics, and the effect was greatest in proximal bowel. Villus height, measured in jejunum, was also greater in growth hormone transgenics. Measurements of mucosal proliferation did not differ between the growth hormone transgenics and wild type. Abundance of insulin-like growth factor-I messenger RNA in bowel was greater in growth hormone transgenics. CONCLUSIONS Chronic growth hormone excess results in increased growth of small bowel mucosa. This effect appears to be specific because it occurred in ad libitum-fed and diet-restricted growth hormone transgenics, influenced villus height, and was more pronounced in upper than lower small bowel. The effect of chronic growth hormone excess does not appear to be secondary to an increase in the rate of mucosal proliferation, suggesting an effect on lifespan of mucosal cells.

Effects of intraluminal epidermal growth factor on mucosal proliferation in the small intestine of adult rats

To determine whether intraluminal administration of epidermal growth factor (EGF) has a trophic effect on small bowel mucosa, catheters were surgically placed in the ileum of adult rats and infused with EGF. Comparing animals receiving EGF (5 micrograms/48 h) with controls, in the ileum mean mucosal ornithine decarboxylase specific activity increased by greater than 200% (p less than 0.001), mean deoxyribonucleic acid specific activity and crypt labeling index increased by greater than or equal to 100% (p less than 0.001), and mean deoxyribonucleic acid content of the mucosa increased by 25% (p less than 0.05). During these studies, the jejunum was not exposed to ileal infusate, as shown with the use of a phenol red marker. Nevertheless, all measurements except deoxyribonucleic acid content increased in the jejunum as well, although to a lesser extent. A greater rise in mucosal ornithine decarboxylase and deoxyribonucleic acid specific activity could be demonstrated in the jejunum when EGF was infused directly into this segment. Mucosal ornithine decarboxylase activity was found to be dose-dependent and to increase in the ileum only after a latent period of 12-24 h. We conclude that intraluminal administration of EGF stimulates a mucosal proliferative response in the small intestine. Intraluminal EGF appears likely to be one of a number of endogenous trophic factors in the small bowel.

Audio-Recorded Guided Imagery Treatment Reduces Functional Abdominal Pain in Children: A Pilot Study

OBJECTIVE: This study was designed to develop and to test a home-based, guided imagery treatment protocol, using audio and video recordings, that is easy for health care professionals and patients to use, is inexpensive, and is applicable to a wide range of health care settings. METHODS: Thirty-four children, 6 to 15 years of age, with a physician diagnosis of functional abdominal pain were assigned randomly to receive 2 months of standard medical care with or without home-based, guided imagery treatment. Children who received only standard medical care initially received guided imagery treatment after 2 months. Children were monitored for 6 months after completion of guided imagery treatment. RESULTS: All treatment materials were reported to be self-explanatory, enjoyable, and easy to understand and to use. The compliance rate was 98.5%. In an intention-to-treat analysis, 63.1% of children in the guided imagery treatment group were treatment responders, compared with 26.7% in the standard medical care–only group (P = .03; number needed to treat: 3). Per-protocol analysis showed similar results (73.3% vs 28.6% responders). When the children in the standard medical care group also received guided imagery treatment, 61.5% became treatment responders. Treatment effects were maintained for 6 months (62.5% responders). CONCLUSION: Guided imagery treatment plus medical care was superior to standard medical care only for the treatment of abdominal pain, and treatment effects were sustained over a long period.

Esophagitis: A frequent consequence of gastroesophageal reflux in infancy

A control group of infants was evaluated to determine criteria for the diagnosis of histologic esophagitis. Based on our observations, histologic esophagitis was defined as four or more intraepithelial neutrophils or one eosinophil per high power field or both. Esophageal biopsy specimens from 33 consecutive infants younger than 2 years who had been examined for clinically significant gastroesophageal reflux (GER) were reviewed for histologic esophagitis. Endoscopy had been performed in each patient, and 4.1 +/- 1.1 (mean +/- SD) biopsy specimens had been obtained above the distal 20% of the esophagus. Twenty (61%) infants had histologic esophagitis, including 15 with intraepithelial eosinophils alone, one with intraepithelial neutrophils alone, and four with both. Older infants (7 to 24 months) with histologic esophagitis were more likely to have moderate to severe inflammation than were infants younger than 7 months of age (P = 0.01). Endoscopic evidence for gross esophagitis was found in six (18%) infants; of these, five had abnormal biopsies, including four with moderate to severe inflammation. Among the 27 infants with a grossly normal esophagus, 14 (52%) had histologic esophagitis, including nine (33%) with moderate to severe inflammation. We conclude that in infants with clinically significant GER: (1) esophagitis is common, (2) histologic esophagitis frequently occurs in the absence of gross endoscopic findings, (3) the likelihood of moderate to severe inflammation increases after 6 months of age, and (4) intraepithelial eosinophils are a sensitive marker for acute inflammation in association with GER.

Nutrient-independent increases in proglucagon and ornithine decarboxylase messenger RNAs after jejunoileal resection

To assess potential mediators of adaptive bowel growth, ileal proglucagon messenger RNA (mRNA) ornithine decarboxylase (ODC) mRNA, plasma enteroglucagons, and plasma glucagonlike peptide I (GLP-I) were analyzed in rats soon after jejunoileal resection or control transection. Analyses were performed before and after refeeding to establish whether responses are nutrient dependent. The elevation of ileal proglucagon and ODC mRNAs within 12 hours after resection and before refeeding shows a nutrient-independent component of the adaptive response. The onset of adaptive growth of the ileum required luminal nutrient but occurred very rapidly, within 4 hours of refeeding. The onset of adaptive growth was accompanied by transient elevation of ileal ODC mRNAs. Ileal proglucagon mRNA and plasma GLP-I levels were also elevated, and these increases were sustained up to 8 days after resection. These early and sustained increases in proglucagon mRNA and plasma GLP-I indicate that in addition to the enteroglucagons, other intestinal proglucagon-derived peptides must be considered as potential mediators of adaptive growth after jejunoileal resection.

Abdominal migraine: Prophylactic treatment and follow-up

BACKGROUND Abdominal migraine is a syndrome characterized by recurrent stereotypic episodes of paroxysmal abdominal pain and nausea and/or vomiting with wellness between episodes. It is often associated with a positive family history of migraine and no other apparent underlying disease. The purpose of this study was to report in patients diagnosed with abdominal migraine the outcome, the effect of prophylactic treatment, and the duration of treatment. METHODS The records of 53 patients who underwent treatment after a diagnosis of abdominal migraine were retrospectively reviewed. Responses to treatment were graded as excellent (cessation of recurrent abdominal pain), fair (persistence of symptoms but milder and less frequent), or poor (no response). Follow-up data were available in 38 patients. Twenty-four patients were treated with propranolol and 12 with cyproheptadine. Four were not treated because of mild and infrequent symptoms. RESULTS Among the children treated with propranolol, 18 (75%) had an excellent response, 2 (8%) had a fair response, and 4 (17%) had no response. In those treated with cyproheptadine, 4 (33%) had an excellent response, 6 (50%) had a fair response, and 2 (17%) had no response. Patients were instructed to continue medication for 6 months or until cycles had stopped. However, 11 of 24 patients (46%) in the propranolol group took medication for less than 6 months and the remaining patients from 6 months to 3 years. Six patients in the cyproheptadine group (50%) took medication less than 10 months and the remaining patients for 10 months to 3 years. CONCLUSION Patients with abdominal migraine may benefit from prophylactic treatment with propranolol or cyproheptadine.

Effects of Fasting, Refeeding, and Intraluminal Triglyceride on Proglucagon Expression in Jejunum and Ileum

Intestinal proglucagon is thought to be synthesized primarily by the distal gut, although the role of proglucagon-derived glucagon-like peptide I (GLP-I) as a major physiological incretin would seem to be associated with production in proximal small bowel. To better characterize the sites of production of proglucagon and GLP-I in the small intestine and evaluate nutrient regulation of small bowel proglucagon and derived peptides, we evaluated the effects of fasting for 72 h and subsequent refeeding or jejunal infusion of long-chain triglyceride (LCT) for 24 h on local expression of proglucagon in proximal and distal small bowel. Proglucagon mRNA abundance and cellular localization were determined and correlated with wet weight of bowel. In jejunum, proglucagon mRNA abundance decreased by 40% with fasting (P < 0.005) and increased with refeeding to levels similar to those of ad libitum-fed animals. In ileum, fasting resulted in a 20% decrease in proglucagon mRNA (P < 0.005); in contrast to jejunum, refeeding did not result in a significant rise in ileal proglucagon mRNA abundance from fasting values. In jejunum, signal intensity of proglucagon mRNA per cell, determined by in situ hybridization, decreased with fasting (P < 0.05) and increased with refeeding (P < 0.005) in proportion to changes in mRNA abundance. Plasma enteroglucagon and GLP-I levels correlated with jejunal proglucagon mRNA. Intrajejunal infusion of LCT increased expression of proglucagon to a greater extent in jejunum than in ileum. In conclusion, enteral nutrient intake stimulates small bowel proglucagon expression; this effect is greater in jejunum than ileum, consistent with greater intraluminal nutrient exposure and the role of jejunum as a source of the major incretin GLP-I.

Olsalazine Versus Sulfasalazine in Mild to Moderate Childhood Ulcerative Colitis: Results of the Pediatric Gastroenterology Collaborative Research Group Clinical Trial

The safety and efficacy of olsalazine sodium was compared to sulfasalazine over 3 months in a multicenter, randomized, double-blind study of 56 children with mild to moderate ulcerative colitis. Twenty-eight children received 30 mg/kg/day of olsalazine (maximum, 2 g/day) and 28 received 60 mg/kg/day of sulfasalazine (maximum, 4 g/day). Side effects were frequent in both groups. Eleven of 28 patients (39%) on olsalazine reported headache, nausea, vomiting, rash, pruritus, increased diarrhea, and/or fever. Thirteen of 28 on sulfasalazine (46%) reported similar side effects and/or neutropenia, and four patients had the drug stopped because of an adverse reaction. After 3 months, 11 of 28 (39%) on olsalazine were asymptomatic or clinically improved, compared to 22 of 28 (79%) on sulfasalazine (p = 0.006). In addition, 10 of 28 patients on olsalazine versus one on sulfasalazine required prednisone because of lack of response or worsening of colitis (p = 0.005). The dose of olsalazine used in this clinical trial was thought to be equivalent to a standard dose of sulfasalazine, but fewer patients on olsalazine improved and a greater number had progression of symptoms when compared to sulfasalazine. Although side effects were slightly less frequent for olsalazine, the number of patients was too small to detect a clinically significant difference.

Fasting Prevents Experimental Murine Colitis Produced by Dextran Sulfate Sodium and Decreases Interleukin-1β and Insulin-Like Growth Factor I Messenger Ribonucleic Acid

Cytokines and insulin-like growth factors (IGFs) are involved in the induction and/or perpetuation of inflammatory bowel disease. The effect of fasting on inflammatory bowel disease was studied in a mouse experimental model of acute colitis caused by adding dextran sulfate sodium (DSS) to drinking water. Animals were either fed ad libitum or fasted (water only) for 2 days before death. Inflammation and tissue damage, measured as a colitis activity score, were markedly reduced in fasted (2.4 +/- 0.1) compared to fed (5.3 +/- 0.1) DSS animals (P < 0.0001). Colon interleukin-1 beta (IL-1 beta), IGF-I, and tumor necrosis factor-alpha messenger RNAs (mRNAs) were quantified by Northern blot hybridization and expressed as a percentage of mRNA abundance in fed controls. In DSS mice, IL-1 beta mRNA was elevated in the fed group (954 +/- 155%; P < 0.001), but was suppressed in fasted animals (71.1 +/- 11%). IGF-I mRNA also was elevated in fed DSS mice (421 +/- 71%; P < 0.01). This increase was attenuated in fasted DSS mice (202 +/- 17%; P < 0.01 compared to fed DSS mice). Tumor necrosis factor-alpha mRNA was increased in fed DSS mice (162 +/- 15%; P < 0.01), but was not significantly lower in fasted animals. By in situ hybridization, IL-1 beta mRNA was localized to the lamina propria of colonic mucosa in fed DSS animals, but was not detectable in other groups. We conclude that fasting has a protective effect on the progression of acute DSS, induced colitis. This is associated with decreased expression of IL-1 beta and IGF-I mRNAs in the colon.