Showing papers in "Gut in 1990"

Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues.

Abstract: The aim of this study was to evaluate the clinicopathological spectrum of eosinophilic gastroenteritis and identify possible difficulties in establishing the diagnosis. All patients with a diagnosis of eosinophilic gastroenteritis, defined by the presence of gastrointestinal symptoms and eosinophilic infiltration of the gut (38), or a radiological diagnosis with peripheral eosinophilia (two), were identified from the Mayo Clinic records; in none was there evidence of extraintestinal disease. Patients were divided into three groups according to the Klein classification: predominant mucosal (23), muscular (12), or subserosal disease (five). A fourth group of patients (10) for comparison had abdominal symptoms and unexplained peripheral eosinophilia but no proven eosinophilic infiltration of the gut. It was found that a history of allergy was reported by 20 of 40 patients with eosinophilic gastroenteritis. Peripheral eosinophilia was absent in nine of 40. The patients with subserosal disease were distinct from the other groups in presentation (abdominal bloating, ascites), higher eosinophil counts and in their dramatic responses to steroid therapy. Otherwise the patients were similar regarding demographic factors, presenting symptoms (abdominal pain, nausea, weight loss, diarrhoea), and laboratory parameters. The ESR was moderately raised in 10 of 40 patients. The disease may affect any area of the gastrointestinal tract; eosinophilic infiltration was documented in the oesophagus in one patient and in the colon in two cases. Endoscopic biopsies missed the diagnosis in five of 40 presumably because of patchy disease. Eosinophilic gastroenteritis should be considered in the differential diagnosis of unexplained gastrointestinal symptoms even in the absence of peripheral eosinophilia.

Precancer and cancer in extensive ulcerative colitis: findings among 401 patients over 22 years.

Abstract: Patients with extensive ulcerative colitis who do not need early surgery have been offered regular examination with the aim of detecting precancerous change (dysplasia) or early colorectal carcinoma. Outpatient visits with clinical examination, sigmoidoscopy, and biopsy were supplemented by two-yearly colonoscopy after the disease course reached 10 years. During the 22 year period from the beginning of 1966 to the end of 1987, 401 patients entered the programme and together contributed 4048 patient-years of observation. Apart from nine patients who left the country, follow up is complete until 1986 or 1987. Colorectal carcinoma developed in 22 patients and, in a further 12, biopsy evidence of precancer, described as severe/high grade dysplasia, was confirmed in a colectomy specimen. The cumulative probability of developing carcinoma was 3% at 15 years, 5% at 20 years, and 9% at 25 years; corresponding figures for precancer or carcinoma, or both were 4%, 7%, and 13%. Five patients died of colorectal carcinoma, two while under regular observation and three after developing carcinoma four to six years after their last attendance. Among the 17 patients who developed carcinoma while under observation, the Dukes stage was A or B in 12. Patients with extensive colitis whose disability does not warrant early surgery have a clinically important cancer risk after the disease has been present for 10 years. Our results suggest that follow up in the manner described reduces the mortality from this complication. Further work is needed to define the optimum method of surveillance and show if it is cost effective.

Dyspepsia in England and Scotland.

Abstract: A validated postal questionnaire has been used to establish the prevalence of dyspeptic symptoms in five geographical locations from the south coast of England to the north of Scotland. The six month period prevalence of dyspepsia in the 7428 respondents to the questionnaire is 41% and equal between the sexes, with similar prevalence rates in the centres studied. There is considerable overlap between upper abdominal symptoms and symptoms of heartburn; 56% of patients with dyspepsia experience both groups of symptoms. Symptom frequency falls progressively with age in men and women, but the proportion of people seeking medical advice for dyspepsia rises with age. One quarter of the dyspeptic patients studied have consulted a general practitioner about their symptoms. This study suggests that the prevalence of dyspepsia in the community has changed little over the last 30 years, despite evidence that the frequency of peptic ulcer disease is falling. Symptom prevalence is unrelated to social class, but this factor is associated with consultation behaviour, the consultation rate rising from 17% in social class 1 to 29% in social class 4. The use of investigations--barium meal and endoscopy--is similarly related to social class; the lowest rate for ulcer diagnosis (4.7%) is found in social class 1 and the highest (17.1%) in social class 5.

Role of interleukin 1 in inflammatory bowel disease--enhanced production during active disease.

Abstract: Interleukin 1 is a polypeptide cytokine produced by various cell types and has been shown to have a major role in inflammatory and immunological responses. In experimental colitis it proved to be a dominant mediator and a reliable marker of inflammation. The aim of the present study was to determine in vitro the extent of production and release of interleukin 1 from colonic mucosa of patients with active untreated inflammatory bowel disease. Colonic mucosal biopsy specimens were obtained during colonoscopy from 17 patients with ulcerative colitis, eight patients with Crohn's disease of the colon, and 16 normal control subjects. Interleukin 1 content was determined in fresh and 24 hour organ cultured mucosa as well as in cultured medium. Interleukin 1 content and release were significantly higher in the inflamed mucosa compared with that of control subjects. Prednisolone inhibited interleukin 1 release in a dose dependent fashion. We conclude that colonic mucosal interleukin 1 content and production is significantly raised in active inflammatory bowel disease and may have a role in the pathogenesis of the inflammatory response. Pharmacological suppression of tissue interleukin 1 production may have a beneficial therapeutic effect.

Bacterial adhesion and disease activity in Helicobacter associated chronic gastritis.

Abstract: Ultrastructural examination of biopsies showing Helicobacter pylori associated chronic gastritis reveals close attachment between gastric surface epithelial cells and the organism. The finding of 'adhesion pedestals', which represents a cellular response to the presence of the organism, is analogous to the response of intestinal cells to enteropathogenic E coli. Thus the development of bacterial attachment sites in H pylori associated gastritis might be an indication of pathogenicity. We have therefore explored the relationship between the proportion of organisms forming attachment sites and histological indices of disease 'activity'. Antral biopsies from 40 patients with H pylori positive gastritis were examined histologically and ultrastructurally, and the percentage of attached organisms compared with subjective assessments of epithelial degeneration, mucin depletion, polymorphonuclear and chronic inflammatory cell infiltration. We found a significant increase in the proportion of attached bacteria in cases showing histological epithelial degeneration, and a significant decrease in cases showing intraepithelial polymorph infiltration. The direct relationship between bacterial attachment and cellular degeneration lends further support to a pathogenic effect. Reduced attachment in the face of polymorph infiltration might indirectly reflect aspects of the immune response--namely, blocking of adhesion by IgA, with complement activation and generation of leucotactic factors.

Involvement of M cells in the bacterial invasion of Peyer's patches: a common mechanism shared by Yersinia enterocolitica and other enteroinvasive bacteria.

Abstract: Recent evidence indicates that ileal Peyer's patches represent the main infection route for Yersinia enterocolitica. In this study transmission and scanning electron microscopy have shown that only a small fraction of bacteria present in the lumen adhere to the follicle-associated murine epithelium with no discernible preference for either M or absorptive cells. Yersiniae attached to M cells are phagocytosed and transported from the lumen into the lamina propria. No invasion of columnar absorptive cells was observed. These data, in combination with recently published reports, indicate that the involvement of M cells is a common step in bacterial invasion of Peyer's patches.

Alternative pathways for hydrogen disposal during fermentation in the human colon.

Abstract: Hydrogen gas, which is produced during fermentation in the human colon, is either excreted in breath or metabolised by gut bacteria through a variety of pathways. These may include methanogenesis, dissimilatory sulphate reduction, and acetogenesis. To determine which of these routes predominates in the large intestine, stools were taken from 30 healthy subjects and incubated as 5% (w/v) slurries with Lintner's starch. In 23 of 30 subjects, methane production was the main method of hydrogen disposal. In the remaining seven, high rates of sulphate reduction were recorded together with raised production of H2S. All samples showed relatively low rates of hydrogen evolution and of acetate formation from CO2 and H2. Sulphate reduction and methanogenesis seem to be mutually exclusive in the colon and this is probably linked to sulphate availability. Sulphate reduction, methanogenesis, and acetogenesis were strongly influenced by pH. Sulphate reduction was optimal at alkaline pH values whereas methane production was maximal at a neutral pH and acetogenesis favoured acidic conditions. Faecal H2S values were related to carriage of sulphate reducing bacteria. These data show that a number of competing pathways for hydrogen disposal are possible in the large gut and that a variety of factors such as colonic pH and sulphate availability can determine which of these mechanisms predominates.

Control of belching by the lower oesophageal sphincter.

Abstract: The mechanism that controls venting of gas from the stomach into the oesophagus was studied manometrically in 14 healthy subjects. The stomach was distended abruptly with one litre of carbon dioxide. Gas reflux was characterised by an abrupt increase in basal oesophageal body pressure to intragastric pressure. Reflux of gas from the stomach into the oesophagus occurred during transient lower oesophageal sphincter relaxations that generally had a pattern distinctly different from swallow-induced lower oesophageal sphincter relaxation. Thus, at the onset of an episode of gas reflux lower oesophageal sphincter pressure had relaxed to 3 mmHg, or less, in 96% of instances. After gas loading of the stomach the prevalence of gas reflux was significantly less when the subjects were supine (1.2/10 min) than when they were sitting (6.8/10 min) (p less than 0.001). The lower oesophageal sphincter relaxations associated with most episodes of gas reflux had a distinctive pattern that resembled those of the lower oesophageal sphincter relaxations associated with acid gastro-oesophageal reflux.

Anorectal manometry in irritable bowel syndrome: differences between diarrhoea and constipation predominant subjects.

Abstract: Anorectal manometry with balloon distension was performed on 28 patients with diarrhoea predominant irritable bowel syndrome, 27 patients with constipation predominant irritable bowel syndrome and 30 normal controls. In the diarrhoea predominant group balloon volumes required to perceive the sensations of gas, stool, urgency of defecation and discomfort were significantly lower than in controls or constipation predominant patients (p less than 0.001). Diarrhoea predominant patients also had a significantly lower rectal compliance than controls or constipation predominant patients (p less than 0.03) but showed no difference in motor activity induced by distension. When the constipation predominant patients were compared with controls the only significant difference that emerged was in the volume at which discomfort was perceived. No significant differences between constipated subjects and controls were found in the distension induced motor activity. Symptom severity and psychological parameters were also recorded and the diarrhoea predominant patients were found to be more anxious than those with constipation (p = 0.04). It proved possible (by comparison with the control group) to identify three abnormal rectal subtypes in patients with irritable bowel syndrome. These were a sensitive rectum (low sensation thresholds, normal or low rectal pressure), a stiff rectum (normal or low sensation thresholds, high pressure) and an insensitive rectum (high sensation thresholds, normal or high pressure) and their distribution varied considerably depending on bowel habit. Some form of rectal abnormality was identified in 75% of diarrhoea predominant patients compared with 30% of constipation predominant subjects (p = 0.002). A sensitive rectum was a particular feature of diarrhoea predominant patients being observed in 57% of patients compared with only 7% of the constipated group (p less than 0.001).

Diagnostic value of the Manning criteria in irritable bowel syndrome.

Abstract: Because unexplained 9functional symptoms9 are a major cause of referral to gastroenterologists, the efficiency of the medical history to lead to a positive diagnosis of irritable bowel syndrome, without resorting to the use of expensive tests, remains a key question. Whilst the six criteria of Manning et al are widely used, data on their validity in discriminating irritable bowel syndrome from healthy controls, irritable bowel syndrome from non-ulcer dyspepsia and especially among irritable bowel syndrome subgroups, are not available. To evaluate this, we studied 361 outpatients who completed a bowel disease questionnaire, which objectively measured Manning9s (and other) criteria. The group included 82 patients with irritable bowel syndrome, 33 with non-ulcer dyspepsia, 101 with organic gastrointestinal disease, and 145 healthy controls. Diagnoses were based on a full and independent clinical evaluation, not on responses to the bowel disease questionnaire. Reliability was assessed by a test-retest procedure. All six of the individual Manning criteria were found to be reliable (median kappa = 0.79). Based on a logistic regression analysis of the discriminatory value of Manning9s criteria, as the number of positive criteria increased, so did the predicted probability of irritable bowel syndrome. This predictive value was highest in younger patients and in females. The Manning criteria discriminated irritable bowel syndrome from organic gastrointestinal disease and from all non-irritable bowel syndrome gastrointestinal disease with a sensitivity of 58% and 42%, and a specificity of 74% and 85%, respectively. Stools that were often loose and watery provided an additional independent criterion for distinguishing irritable bowel syndrome from non-irritable bowel syndrome. Thus, symptoms can be used to diagnose irritable bowel syndrome positively, but Manning9s criteria are not highly sensitive.

Osteoporosis and skeletal fractures in chronic liver disease.

Abstract: In order to determine the prevalence and severity of hepatic osteodystrophy by non-invasive means we compared 115 consecutive ambulant patients with histologically proven chronic liver disease to 113 age and sex matched control subjects. Methods used included the assessment of fracture prevalence rates, spinal radiography, and measurements of bone mineral density in the spine and the forearm. Spinal and peripheral fractures were more prevalent in the patients than in the control subjects (p less than 0.03 and p less than 0.01 respectively). The type of the underlying liver disease did not significantly affect the fracture prevalence rates, but alcoholic patients sustained more peripheral fractures than patients with other hepatic disorders (p less than 0.05). The bone mineral densities of the spines and the forearms were significantly reduced in male patients of all age groups and in female patients aged 60 years or more (p less than 0.001 for men and p less than 0.01 for women for both measurements). The prevalence rates of spinal and forearm osteoporosis were twice as high among patients with liver disease than in control subjects regardless of the definitions used. The presence of cirrhosis and hypogonadism were major risk factors for development of both spinal (Beta coef = 0.190 and 0.176; SE = 0.079 and 0.086 respectively) and forearm osteoporosis (Beta coef = 0.20 and 0.29; SE = 0.073 and 0.80 respectively). Spinal bone density was the predominant determinant of spinal fractures (Beta coef = -0.007; SE = 0.001), while hypogonadism (Beta coef = 0.363; SE = 0.075) and cirrhosis (Beta coef = 0.185; SE = 0.068) were the major predictors of peripheral fractures. The concentrations of serum calcium and serum vitamin D metabolites and the use of corticosteroids were apparently without effect on the prevalence of skeletal fractures or bone density.

Role of reactive oxygen metabolites in experimental colitis.

Abstract: Reactive oxygen metabolites are potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. To evaluate their role in inflammatory bowel disease, we investigated the effects of lowering the activities of reactive oxygen metabolites in experimental colitis induced by intracolonic administration of acetic acid in rats. Intracolonic administration of 5% acetic acid caused severe inflammation (mean (SEM) inflammatory score was 24.3 (0.7) of a maximum score of 32). Acetic acid at 2.5% produced moderate inflammation (score = 17 (1.4) v 4.0 (0.5) in control rats). This lower dose was used for subsequent experiments. Specific superoxide anion scavenger methoxypolyethylene glycol:superoxide dismutase, and reactive oxygen metabolites scavenger, sulfasalazine, significantly decreased the severity of inflammation (scores: 8 (4.4) and 9.8 (2.2) respectively). The xanthine oxidase inhibitors, tungsten and pterin aldehyde, failed to improve inflammation but another xanthine oxidase inhibitor, allopurinol, a compound with known superoxide anion scavenging effect, did limit the inflammation (10(2)). Inhibition of hydroxyl radical production by deferoxamine or lowering hydroxyl radical values by a scavenger, dimethyl sulfoxide, did not affect the severity of inflammation. These data suggest: (1) that reactive oxygen metabolites play an important role in experimental colitis, (2) that the xanthine oxidase pathway is not a major source of reactive oxygen metabolites in colitis, and (3) that tissue injury in experimental colitis is not caused by generation of hydroxyl radicals.

Incidence of large oesophageal varices in patients with cirrhosis: application to prophylaxis of first bleeding.

Abstract: Because several studies have suggested that beta blockers are effective in the prophylaxis of first variceal bleeding in cirrhosis, screening for oesophageal varices might be appropriate. We prospectively studied 84 cirrhotic patients without obvious evidence of large oesophageal varices and previous bleeding during a mean follow up of 16 months. At entry to the study 41 patients had no oesophageal varices and in 43 these were grade 1. The subsequent percentages of patients without large oesophageal varices were 74% at one year and 52% at two years. Univariate analysis showed that a longer duration of cirrhosis (p less than 0.05) and grade 1 oesophageal varices at entry (p less than 0.001) were predictive factors for the occurrence of large oesophageal varices, whereas, multivariate analysis showed that the initial size of the oesophageal varices (p less than 0.001), a high initial Child-Pugh score, and a smaller improvement in Child-Pugh score during the study were independent risk factors. Among patients with grades 0 and 1 oesophageal varices at the start of the study the proportions with large oesophageal varices at two years were 31% and 70% respectively. We have calculated that, accepting a maximum risk of first bleeding of 10% without prophylactic treatment, a patient without oesophageal varices should be screened endoscopically every other year, while a patient with grade 1 disease should benefit from one annual upper gastrointestinal endoscopy.

Oxygen free radicals in acute pancreatitis of the rat.

Abstract: This study aimed to assess the role of oxygen free radicals in acute pancreatitis. Acute pancreatitis was induced in rats by infusion of the CCK-analogue cerulein (5 micrograms/kg per hour) for 30 minutes, 3.5 hours, and 12 hours. After the infusion, serum enzymes and conjugated tissue dienes and malondialdehyde were measured and tissue samples were subjected to electron and light microscopy. Electron microscopy after 30 minutes showed moderate intracellular alterations. After 3.5 hours of cerulein infusion interstitial oedema and intravascular margination of granulocytes in the pancreatic gland were seen. After 12 hours histological evaluation showed pronounced zymogen degranulation, extensive tissue necrosis, and migration of granulocytes into the tissue. Amylase and lipase activities increased 15 and 35-fold respectively during this time. After 30 minutes of cerulein infusion conjugated dienes and malondialdehyde increased, they reached their peak after 3.5 hours and decreased to normal values after 12 hours. Treatment with superoxide dismutase (100,000 U/kg/hour) and catalase (400,000 U/kg/hour) either before or after the start of the cerulein infusion prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue oedema and inflammatory response, however, were not affected in any of the treated rats. Oxygen free radicals are instrumental in the development of acute pancreatitis. Even after its onset, scavenger treatment reduced the tissue damage normally observed.

Cancer in an ileoanal reservoir: a new late complication?

Abstract: The functional success rate of the ileoanal reservoir procedure for ulcerative colitis is quite high. Despite the few early and late complications described there is now wide-spread acceptance of this procedure in the management of ulcerative colitis. We report a patient who developed an adenocarcinoma in the rectal cuff four years after having a pelvic pouch procedure. This new late complication brings to light several points including the importance of a radical total mucosectomy. The purpose of this paper is to discuss concern as to whether or not this procedure is indicated in colitis patients in whom severe dysplasia is the primary indication for surgery.

Inappropriate hypergastrinaemia in asymptomatic healthy subjects infected with Helicobacter pylori.

Abstract: An ELISA test determined serologically that eight of 95 apparently healthy men (aged 19-26 years) had an asymptomatic infection with Helicobacter pylori at the time of simultaneous measurement of 24 hour intragastric acidity and 24 hour plasma gastrin concentration. There was no significant difference in the median integrated 24 hour intragastric acidity between the H. pylori positive and H. pylori negative subjects (688 and 842 mmol/h/l; p = 0.271, respectively), whereas the median integrated 24 hour plasma gastrin concentration was significantly higher in the H pylori positive than in the H pylori negative subjects (389 and 198 pmol/h/l; p less than 0.001). Longterm hypergastrinaemia, associated with persistent H pylori infection, could be a cause of the increased parietal cell mass that is considered characteristic of duodenal ulcer patients.

Occupational distribution of inflammatory bowel disease among German employees.

Abstract: Previous reports have shown that both Crohn's disease and ulcerative colitis affect people in white collar occupations associated with higher income and higher social class more frequently than other groups in the population. This study sought to carry these analyses one step further and investigate the distribution of inflammatory bowel disease by individual occupations. The German social security statistics for 'rehabilitation' were used to assess the occupational distribution of Crohn's disease and ulcerative colitis. From 1982 to 1988, a total of 12,014 people were granted rehabilitation as a result of inflammatory bowel disease. Low male prevalence of inflammatory bowel disease was found among bricklayers, road construction workers, unskilled workers in brick and stone, unskilled labourers, and security personnel. Low rates were found among women employed in cleaning and maintenance, and in those without occupation. In contrast, a high male prevalence was found among instrument makers, electricians, bakers, and technical assistants. Among female employees, inflammatory bowel disease was significantly associated with sales representatives, office workers, health occupations, and hairdressers. These associations were found in the complete data for 1982-8 as well as in the separate data for the two half periods 1982-5 and 1986-8. Highly significant correlations between the occupational distribution of Crohn's disease and ulcerative colitis were found among both male and female employees. It seems that occupations involving work in the open air and physical exercise are protective, while being exposed to air conditioned artificial working conditions or extended and irregular shift working confer a risk of contracting inflammatory bowel disease.

Factors affecting colectomy rate in ulcerative colitis: an epidemiologic study.

Abstract: Factors affecting colectomy rate were studied in a retrospective population based series of 1586 patients with ulcerative colitis, in Stockholm County during 1955-84. Five hundred and sixty eight patients (36%) had total colitis at diagnosis, 603 patients (38%) left sided colitis, and 397 patients (25%) proctitis. During a median period of observation of 13 years 514 patients were treated by colectomy. The five, 10, and 25 year cumulative colectomy rate were 20% (CI 18-22%), 28% (CI 26-30%), and 45% (CI 41-49%) respectively. The main factor affecting the colectomy rate was the extent of disease at diagnosis. Patients with total colitis showed a five, 10, and 25 year cumulative colectomy rate of 32% (CI 28-36%), 42% (CI 38-46%), and 65% (CI 58-72%) respectively. Ten per cent of the 1586 patients had a colectomy during the first year after diagnosis, 4% during the second year and 1% during subsequent years. The age at diagnosis and sex did not affect the cumulative colectomy rate. Elective colectomy was performed in 322 cases (63%) and acute colectomy in 192. The duration of disease before colectomy fell during the study period due to a more standardised criteria for colectomy in severe attacks. One hundred and twenty nine (66%) of the acute colectomies were performed within two years from diagnosis.

Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis.

Abstract: Eicosanoids are modulators of defensive and inflammatory processes in the gut mucosa, and may be involved in the pathogenesis of chronic inflammatory lesions of the bowel. As omega-3 fatty acids compete with the omega-6 as precursors of eicosanoid synthesis, we compared the effects of dietary supplementation with either sunflower (source of omega-6) or cod liver (source of omega-3) oil on the development of chronic granulomatous lesions in the rat colon. After four weeks on the supplemented diets, plasma omega-6 fatty acid content was significantly higher in the sunflower group, while omega-3 fatty acids predominated in the cod liver group. Inflammatory colitis was then induced by intracolonic administration of trinitrobenzene sulphonic acid. Luminal eicosanoid release, as measured by radioimmunoassay of intracolonic dialysis fluid, increased significantly after the challenge in both groups. Generation of prostaglandin E2 (PGE2) and leucotriene B4 (LTB4) peaked by day 3 and thereafter declined; thromboxane B2 (TXB2), instead, continued to increase from day 3 to 20 in sunflower fed rats, whereas this change was blunted in cod liver animals. The rats were killed 20, 30, or 50 days after the induction of colitis, and the colonic lesions were scored macroscopically (adhesions to surrounding tissues, strictures, ulcerations, and wall thickness) and histologically (ulceration, inflammation, depth of the lesions, and fibrosis). In cod liver animals, the damage score was markedly reduced by day 30, and inflammation and ulceration were almost absent by day 50. In conclusion, a fish oil diet prevents the increase in thromboxane in the chronic state of inflammation and shortens the course of the colonic disease by diminishing both the severity of the lesions and their progression to chronicity.

Mechanisms of acid reflux associated with cigarette smoking.

Abstract: Studies were done to evaluate the lower oesophageal sphincter function of chronic smokers compared with non-smokers and to ascertain the acute effects of smoking on the sphincter and the occurrence of acid reflux. All subjects (non-smokers, asymptomatic cigarette smokers, and smokers with oesophagitis) were studied postprandially with a lower oesophageal sphincter sleeve assembly, distal oesophageal pH electrode, and submental electromyographic electrodes. The two groups of cigarette smokers then smoked three cigarettes in succession before being recorded for an additional hour. As a group, the cigarette smokers had significantly lower lower oesophageal sphincter pressure compared with non-smokers but the sphincter was not further compromised by acutely smoking cigarettes. Cigarette smoking did, however, acutely increase the rate at which acid reflux events occurred. The mechanisms of acid reflux during cigarette smoking were mainly dependent upon the coexistence of diminished lower oesophageal sphincter pressure. Fewer than half of reflux events occurred by transient lower oesophageal sphincter relaxations. The majority of acid reflux occurred with coughing or deep inspiration during which abrupt increases in intra-abdominal pressure overpowered a feeble sphincter. We conclude that cigarette smoking probably exacerbates reflux disease by directly provoking acid reflux and perhaps by a long lasting reduction of lower oesophageal sphincter pressure.

Short chain fatty acids dilate isolated human colonic resistance arteries.

Abstract: Colonic biopsy specimens were obtained from patients undergoing surgery for carcinoma of the rectum. Colonic resistance arteries (internal diameter 178-345 microns) were dissected out under the microscope and mounted in a microvascular myograph capable of measuring isometric tension development. Experiments were designed to test compounds trophic to the gastrointestinal tract--namely, glutamine and the three short chain fatty acids, acetic, propionic, and butyric acid, for effects on vascular tone. Glutamine in concentrations up to 30 mM neither constricted nor dilated the resistance arteries. The three short chain fatty acids alone and in combination, however, caused a concentration-dependent (range 0.1-30 mM) dilatation of resistance arteries preconstricted with 50 mM K+, and this relaxant effect was unaffected by removal of the endothelium, presence of indomethacin, and preconstriction with vasopressin. These data suggest that the trophic effect of glutamine on intestinal mucosa cannot be explained through actions of this compound on the resistance vasculature. In contrast, the relaxant effect of short chain fatty acids on resistance arteries in vitro suggests that these compounds may be able to improve the colonic microcirculation in vivo, thereby providing an explanation for their trophic effect on intestinal mucosa.

Why do patients with ulcerative colitis relapse

Abstract: To determine the factors responsible for ulcerative colitis relapse a cohort of 92 patients (18 to 78 years, 50 men) with clinically inactive disease have been followed for over 48 weeks. At 12 weekly intervals patients were asked, by means of standardised questionnaires, about infections, compliance with maintenance medication, new drug treatment, dietary changes, episodes of non-bloody diarrhoea, life stresses, and feelings of anxiety and depression. Thirty five patients (38%) relapsed (median interval 17 weeks, range three to 46 weeks). Patients who relapsed had a higher previous relapse rate than non-relapsers (p less than 0.001) and a shorter time from previous relapse to trial entry (p less than 0.05). Other clinical characteristics were equally matched in the two groups. Between and within group comparisons revealed that upper respiratory tract symptoms, antibiotic ingestion, analgesic intake, diarrhoeal episodes and stressful life events were no more common in the four weeks before relapse than before routine attendance. Anxiety and depression ratings were also similar in the two groups. The timing of ulcerative colitis relapse showed a clear seasonal pattern with 26 patients relapsing from August to January and only nine from January to July (p less than 0.001). In addition, a retrospective case note analysis revealed significant seasonality of onset of ulcerative colitis. We conclude that seasonal factors may contribute to both onset and relapse of ulcerative colitis.

Antibody to selected strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and Candida albicans in Crohn's disease.

Abstract: IgG serum antibody was measured by ELISA in patients with Crohn's disease (15), ulcerative colitis (15), and in normal controls (15) to 12 strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and to the two major serotypes of the commensal yeast Candida albicans. Antibody to 11 of the 12 strains of S cerevisiae was raised in patients with Crohn's disease but not in patients with ulcerative colitis when compared with controls (p less than 0.001). The pattern of antibody response to these 11 strains was variable, however, suggesting the likelihood of antigenic heterogeneity within the species. Antibody to C albicans was not significantly different in patient and control groups. The specificity of this unusual antibody response in Crohn's disease for S cerevisiae suggests that it is not simply the result of a generalised increase in intestinal permeability. Furthermore, because brewing and baking strains detected the response, the relevant antigen(s) are presumably common in the diet. Hypersensitivity to dietary antigens may be involved in the pathogenesis of Crohn's disease, and the role of S cerevisiae requires further investigation.

Changes in rectal sensitivity after hypnotherapy in patients with irritable bowel syndrome.

Abstract: Fifteen patients with the irritable bowel syndrome were studied to assess the effect of hypnotherapy on anorectal physiology. In comparison with a control group of 15 patients who received no hypnotherapy significant changes in rectal sensitivity were found in patients with diarrhoea-predominant irritable bowel syndrome both after a course of hypnotherapy and during a session of hypnosis (p less than 0.05). Although patient numbers were small, a trend towards normalisation of rectal sensitivity was also observed in patients with constipation-predominant irritable bowel syndrome. No changes in rectal compliance or distension-induced motor activity occurred in either subgroup nor were any changes in somatic pain thresholds observed. The results suggest that symptomatic improvement in irritable bowel syndrome after hypnotherapy may in part be due to changes in visceral sensitivity.

Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion.

Abstract: To compare the disposition of 5-aminosalicylic acid (5-ASA) and its acetylated metabolite during treatment with olsalazine and mesalazine, 14 patients with inactive ulcerative colitis were randomly assigned to olsalazine (1 g twice daily) and the mesalazines, Asacol (800 + 400 + 800 mg daily), Pentasa (750 + 500 + 750 mg daily), and Salofalk (750 + 500 + 750 mg daily) in a crossover design trial so that all received each drug for seven days. Intraluminal colonic concentrations of 5-ASA were estimated after five days by the method of equilibrium in vivo dialysis of faeces. A predose serum sample and a 24 hour urine collection were obtained on day seven. The 5-ASA and acetyl-5-aminosalicylic acid (Ac-5-ASA) values were determined by high performance liquid chromatography. Olsalazine almost doubled the colonic concentrations (mean 23.7 (SEM) (1.9) mmol/l) of its therapeutically active ingredient (5-ASA) compared with equimolar doses of Pentasa (12.6 (2.2) mmol/l; p less than 0.0003) and Salofalk (15.0 (2.0) mmol/l; p less than 0.003). At the same time, olsalazine treatment was associated with lower serum concentrations and urinary excretions (p less than 0.05) of 5-ASA and Ac-5-ASA compared with the mesalazine preparations. The low systemic load of 5-ASA provided by olsalazine reduces the potential risk of nephrotoxicity during long term treatment.

Effect of coffee on distal colon function.

Abstract: Ninety nine healthy young volunteers (58 men, 34 women, aged 17-27 years) answered a questionnaire concerning their bowel habit with particular reference to the effects of beverages. Twenty nine per cent (63% women) claimed that coffee induced a desire to defecate. The rectosigmoid motor responses to black, unsweetened coffee were then investigated by multiport manometry in 14 healthy-subjects (12 men, two women, eight of whom claimed coffee caused a desire to defecate (responders). Results revealed an increase in motility index within four minutes after ingestion of both regular and decaffeinated coffee (p less than 0.05) in the eight responders, but not in the six non-responders. The increase in rectosigmoid motility induced by coffee lasted at least 30 minutes. There was no increase in the motility index in any subject after a drink of hot water. These results suggest that drinking coffee can stimulate a motor response of the distal colon in some normal people.

High grade dysplasia of the gastric mucosa: a marker for gastric carcinoma.

Abstract: The natural history of gastric epithelial dysplasia and its relation to gastric cancer are ill defined. A consecutive series of 40 patients with an initial diagnosis of gastric epithelial dysplasia based on examination of endoscopic biopsies has been reviewed to determine the clinical outcome and to evaluate a two tier histological grading system as a predictor of the risk of cancer. On review, only 20 of the 40 patients were considered to have true dysplasia: seven patients had low grade dysplasia and 13 had high grade dysplasia. Of the 13 patients with high grade dysplasia, 11 (85%) were found to have gastric cancer within 15 months. Of the 10 patients with high grade dysplasia who underwent gastrectomy, six were found to have early gastric cancer, three had cancer invading into the muscularis propria, and none had lymph node metastases. High grade dysplasia is thus a marker of gastric cancer. Moreover, the cancers associated with high grade dysplasia are usually pathologically favourable and curable. The finding, by an experienced pathologist, of high grade dysplasia in two separate sets of endoscopic biopsies is therefore an indication for radical surgical treatment, provided that the patient's age and general condition permit such an approach.

Inflammation in ileal reservoirs: 'pouchitis'.

Abstract: Unlike conventional ileostomies, ileal faecal reservoirs often become inflamed. The first reservoirs were continent ileostomies and follow up studies soon showed histological features of mucosal inflammation.' Similar changes were found when pelvic ileal pouches were examined.2 The clinical entity caused by mucosal inflammation in a pouch was first recognised in continent ileostomies3 and later in pelvic ileal pouches.4 Clinical 'pouchitis' has been widely recognised since.3 5 '3 It is characterised by diarrhoea, sometimes containing blood and often by long remissions between relapses. Only a few patients have sustained symptoms. Some patients also have fever and malaise. Abdominal discomfort is uncommon. Although extra-intestinal manifestations such as arthritis and skin lesions are infrequent their intensity often parallels that of the intestinal symptoms.'4 Diarrhoea is the major clinical problem and may be severe enough to cause dehydration.

Symptoms and investigative findings in 145 patients with tuberculous peritonitis diagnosed by peritoneoscopy and biopsy over a five year period.

Abstract: This study analysed clinical features and laboratory investigations in 145 patients with tuberculous peritonitis diagnosed by peritoneoscopy at this hospital between 1984 and 1988. Tuberculous peritonitis was found in 2% of all patients with tuberculosis and in 59.8% of all those with abdominal tuberculosis admitted to the hospital during the study period. Tuberculous peritonitis was more common in women than men (1.4:1) and was most frequently encountered in the third and fourth decades of life. The commonest presenting symptoms were abdominal swelling (73.1%), fever and night sweats (53.8%), anorexia (46.9%), weight loss (44.1%), and abdominal pain (35.9%). The mean duration of symptoms was 1.5 months. Ascites was the commonest (95.2%) physical sign. Tuberculin skin testing was positive in 57.6% of patients (n = 118). The mean erythrocyte sedimentation rate was 75 mm/1st hour (n = 58). Chest radiography on 98 patients showed pleuropulmonary pathology in 40 patients (40.8%). Sputum examination confirmed active pulmonary tuberculosis in 26 patients. The ascitic fluid was an exudate in 96.4% and a transudate in 3.6% of patients, with 91.3% showing a straw coloured ascites. Cirrhosis, detected by biopsy specimen, was a finding in 6.2% of patients.