Showing papers in "Gut in 1981"

Short chain fatty acids in the human colon.

Abstract: The human colon contains a luxuriant mixed culture of bacteria, probably at least 175 g. The special property of these bacteria is their metabolism, which is in the main strictly anaerobic, the end-products being primarily the short chain, or volatile, fatty acids, acetic, propionic, and butyric acid. These are the principal known anions in the colon but, although this has often becni rcported,' little thought has been given to the possible implications.

Effect of gel-forming gums on the intestinal unstirred layer and sugar transport in vitro.

Abstract: The effect of two gel-forming polysaccharide gums, guar gum and Na-carboxymethyl-cellulose (CMC), on glucose transport in vitro was investigated using everted sacs of rat jejunum. The gums were added to the mucosal bathing media to give apparent viscosities in the range of 1-110 Pascal seconds X 10(-3), mPa.s(cP). Serosal glucose transport fell steeply by about 60% as the viscosities of the mucosal media rose to 20mPa.s, and levelled off thereafter. A similar effect was observed in sacs preincubated with guar gum (15 minutes) and exposed to glucose in a subsequent guar-free incubation. Glucose transport with and without the addition of guar gum was found to be sensitive to mucosal stirring, so that, when shaken at 130 oscillations per minute, sacs exposed to guar gum (0.25 %, viscosity c.a. 16 mPa.s (cP) transported glucose at a similar rate to sacs incubated without guar at 80 oscillations per minute. By measuring the time course for the establishment of osmotic induced potentials, it was shown that incubation with guar or CMC led to an increase in the apparent thickness of the unstirred fluid layer overlying the mucosa (guar-free thickness = 317 +/- 15 mu, guar treated thickness = 468 +/- 25 mu). It is suggested that the presence of a polysaccharide gum in the fluid film surrounding the villi increases its viscosity, and thus gives rise to a thickening of the rate-limiting unstirred layer. If such an effect occurs in vivo, this could contribute to the diminished post-prandial glycaemia observed in human subjects fed guar gum.

Preparation and purification of lymphocytes from the epithelium and lamina propria of murine small intestine.

Abstract: Existing methods for the production of lymphocytes from the small intestine have proved unsatisfactory when applied to the mouse. We report here a new method for the production of highly pure suspensions of lymphoid cells from the epithelial layer and lamina propria of mouse small intestine. The production and purification methods are described in detail. At least ten million lymphocytes are obtainable from each small intestine from either the epithelium or lamina propria and the cell suspensions are shown to be little contaminated by non-lymphoid cells. Preliminary analysis of the two cell types indicates that they belong either to two separate populations or to one population in very different stages of differentiation. The use of purified lymphoid cells from the epithelium and lamina propria of the small intestine may enable examination of the generation of cytotoxicity towards gut epithelial cells; this may be important in the development of inflammatory bowel diseases.

Sulphasalazine and male infertility: reversibility and possible mechanism.

Abstract: Earlier observations on infertility related to sulphasalazine treatment were extended and semen samples obtained from 28 patients with inflammatory bowel disease on treatment with sulphasalazine at 2-4 g per day. Semen was examined for changes in density, motility, and morphology before, during, and after withdrawal of sulphasalazine. Gross semen abnormalities were seen in 18 patients on this drug for more than two months. Semen quality improved after sulphasalazine had been withdrawn for more than two months and 10 pregnancies are reported after sulphasalazine withdrawal. Preliminary endocrine and acetylator phenotype studies do not elucidate the mechanism of this important new side-effect of this drug. The time course of the drug's effect on semen quality is consistent with the hypothesis that sulphasalazine or a metabolite, possibly sulphapyridine, is directly toxic to developing spermatozoa. These studies confirmed the preliminary report and suggest that prolonged treatment with sulphasalazine may universally depress semen quality and cause reversible infertility.

Restorative proctocolectomy with ileal reservoir: a pathophysiological assessment.

Abstract: A metabolic and physiological assessment was carried out in 14 patients who had undergone restorative proctocolectomy with ileal reservoir more than six months previously. The haemoglobin was normal in all but one and plasma electrolytes and serum albumin, calcium, phosphorus, and red cell folate estimations were normal in all. Five patients had low serum iron levels of whom one had an iron deficiency anaemia. The 24 hour faecal fat output was normal in all patients and there was no case of vitamin B12 malabsorption as judged by the Schilling test, although four patients had marginally low values. These were not associated with increased bacterial counts in the faeces within the reservoir and there was no evidence to support a diagnosis of stagnant loop syndrome. Inflammation of the reservoir mucosa was, however, associated with higher counts of aerobic bacteria than in cases where inflammation was absent. Subtotal villous atrophy or inflammation was seen in biopsies of the reservoir in six patients. The mean faecal output per 24 hours was 659 +/- 259 g and the mean reservoir volume was 330 +/- 78 ml. Mean resting anal canal pressure was significantly lower in patients with a mucous leakage per anum than in those without, while manometry of the reservoir showed no alteration of pressure over a period of one hour before and after a meal. A positive rectosphincteric reflex was observed in nine patients.

The pancreas as a single organ: the influence of the endocrine upon the exocrine part of the gland.

Abstract: Vascular anatomy of the pancreas In 1882, Kuhne and Lea' noticed that the pancreas of the living rabbit contained many discrete vascular regions, and they compared the vessels of these regions with glomerular tufts. It was not until 1893 that Laguesse2 suggested that the vascular regions might be secreting something into the blood which prevented the normal animal from becoming diabetic. He suggested that the vascular areas be called the islets of Langerhans, in memory of their discoverer.3 Subsequently, several authors have compared the morphology of endocrine and exocrine vessels and have demonstrated that the capillaries of the islets are wider and more densely arranged than are the exocrine capillaries surrounding the islet.4-8 These authors, with one exception, noticed that capillary connections existed between the vessels of the islets and the capillaries of the exocrine gland. The presence of these capillary connections is central to the theme of this review. As islets receive their blood supply via short arterioles6 7 and as the capillaries of the islets are often wider than those of the exocrine tissue, it is reasonable to assume that the capillary pressure is higher in the islet vessels than in the adjacent exocrine vessels. So where islet-exocrine connections exist the direction of flow should be predominantly outwards. This centrifugal flow has been demonstrated by cinematography in the pancreas of the living rabbit.9 10 The frequency of these endocrine-exocrine connecting vessels (Figure) has been shown by several authors, using a variety of injection techniques.1'-'5 Two authors have suggested that the centrifugal flow from endocrine to exocrine pancreas plays a significant role in the metabolic activity of the exocrine pancreas.16 17 This review considers the evidence for this relationship, which depends upon the presence of very high concentrations of hormones in the capillaries leaving the islet under different metabolic conditions.

Comparison of the effects of ranitidine, cimetidine and placebo on the 24 hour intragastric acidity and nocturnal acid secretion in patients with duodenal ulcer.

Abstract: Twenty-four hour intragastric acidity and nocturnal acid secretion were measured in 10 males with duodenal ulcer in four separate 24 hour studies, during which the subjects ate normal meals, had unrestricted physical activity, and consumed their customary quantities of tobacco. The medication consisted of either placebo, cimetidine 200 mg tds and 400 mg at night, or ranitidine 150 mg bd, or 200 mg bd. Ranitidine 150 mg bd decreased mean 24 hour hydrogen ion activity from 41.8 mmol/l to 13.1 mmol/l (-69%, P less than 0.001) and nocturnal acid output from 6.1 mmol/h to 0.6 mmol/h (-90%, P less than 0.01). This degree of inhibition was significantly greater than that due to cimetidine (P less than 0.001 for 24 hours acidity, less than 0.05 for night time acid output). Plasma concentrations of ranitidine were greater than the IC50 for more than eight hours after the 150 mg dose. Ranitidine 200 mg conferred no additional advantage. Ranitidine 150 mg bd should be tested in therapeutic trials.

Incidence of sulphasalazine-induced male infertility.

Abstract: Sperm analysis of 21 patients taking sulphasalazine for inflammatory bowel disease revealed that 86% had abnormal semen analysis and 72% had oligospermia.

Demonstration of a pH gradient across mucus adherent to rabbit gastric mucosa: evidence for a 'mucus-bicarbonate' barrier.

Abstract: We examined the ability of the mucus layer adherent to isolated pieces of rabbit gastric mucosa to maintain a pH gradient across it. Using antimony microelectrodes, a stable pH gradient was detected from pH 2.31 +/- 0.04 on the luminal side to pH 7.26 +/- 0.15 (n = 22) on the epithelial side of the mucus layer. The gradient was maintained for at least 60 minutes. A metabolic inhibitor, potassium cyanide, markedly reduced the tissues' ability to maintain this pH gradient, suggesting involvement of an active cellular process, probably that of bicarbonate secretion. These observations provide additional evidence in favour of a 'mucus-bicarbonate' barrier which may be of importance in protecting the underlying gastric mucosa.

Renal failure in fulminant hepatic failure and terminal cirrhosis: a comparison between incidence, types, and prognosis.

Abstract: Forty patients with terminal cirrhosis and 40 patients with fulminant hepatic failure-all consecutively admitted-were studied with regard to incidence, types, and prognosis of complicating renal insufficiency. Renal failure was considered present when the serum creatinine was greater than 0.20 mmol/l. Of the patients with cirrhosis 26 (65%) developed renal failure. In 15 the type was functional, in three due to acute tubular necrosis, and in eight indeterminable. Of the patients with fulminant hepatic failure 22 (55%) had renal insufficiency; of these 13 had functional renal failure, five acute tubular necrosis, and in four the type was indeterminable. In both categories of patients, renal failure was equally frequent among patients with or without gastrointestinal bleeding and with or without ascites or diuretic therapy. The biochemical tests of liver function were similar in patients with or without renal failure in both categories. The mean renal blood flow in seven unselected patients with fulminant hepatic failure was reduced in the same order as previously observed in patients with cirrhosis. In terminal cirrhosis the mortality rate was 88% in the presence of renal failure, 71% in its absence (p greater than 0.05), while the same figures in fulminant hepatic failure were 100% and 67% (p less than 0.05). The incidence, relative frequency, and prognosis of renal failure were not different in the two conditions, indicating identical pathophysiological circumstances.

Effect of sulphasalazine in patients with active Crohn's disease: a controlled double-blind study.

Abstract: Sulphasalazine [SASP] is widely used in the medical treatment of Crohn’s disease but until recently its efficacy has not been studied by controlled trials. Therefore, we started a few years ago a study to evaluate the efficacy of SASP in the treatment of patients with active Crohn’s disease.

Assessment of appropriate laboratory measurements to supplement the Crohn's disease activity index.

Abstract: The ability of 11 laboratory parameters to reflect the degree of activity of Crohn's disease, using a clinical index as reference point was compared by means of multiple stepwise regression analysis. Activity was best defined in decreasing order by orosomucoid, sedimentation rate, C reactive protein, alpha-1-antitrypsin, albumin, haematocrit, IgM, circulating immune complexes, serum iron, IgG, and IgA. The haematocrit, the only laboratory measurement in the Crohn's disease activity index developed by the National Cooperative Study Group in the USA, is less discriminant than acute phase reactants. Only three parameters-namely, orosomucoid, sedimentation rate, and C reactive protein-have a significant weight and should be complementary to a simple clinical index.

Immunohistological characterisation of intraepithelial lymphocytes of the human gastrointestinal tract.

Abstract: Intraepithelial lymphocytes (IEL) of the normal human stomach, small intestine, and large intestine have been characterised in tissue sections by a double marker immunofluorescent technique. A panel of reagents was used in combination, including antisera to T lymphocyte antigen (HuTLA), Ia-like (p28, 33) antigens and immunoglobulin subclasses, as well as a mouse monoclonal antibody to a human leucocyte antigen (HLe-1). In stomach and proximal small intestine over 95% of IEL were T lymphocytes (HLe-1+, HuTLA+). The proportion was slightly lower in the colon and rectum (85--95%). IEL rarely expressed Ia-like antigens. B lymphocytes were not seen within the epithelium of any of the tissues examined. The functions of IEL must be assessed in the light of the finding that they are predominantly T cells.

Randomised trial of endoscopic argon laser photocoagulation in bleeding peptic ulcers.

Abstract: Emergency endoscopy on 332 patients with acute upper gastrointestinal bleeding showed that 178 had peptic ulcers; 28 of these were actively bleeding (spurting) and 108 showed stigmata of recent haemorrhage (vessels or spots in the ulcer base) suggesting a risk of rebleeding. These 136 patients were randomly allocated to Argon laser photocoagulation or to no additional therapy (controls) at the time of initial endoscopy. All patients received conventional management, and the controlling clinicians did not know whether or not the laser had been used in any individual patients. The laser system proved both simple and safe in use. Initial haemostasis was achieved by the laser in 10 of 15 'spurting vessels', but four of 13 'control' spurting vessels also stopped bleeding spontaneously. Overall, there were no statistically significant differences between the laser treated and control groups in terms of rebleeding, the need for surgical intervention, or death. These results require amplification in larger trials, and comparison with other studies using different protocols and other haemostatic methods.

Rate and pattern of epithelial cell proliferation in ulcerative colitis.

Abstract: We investigated the pattern of proliferation of epithelial cells in rectal mucosa taken from normal individuals and patients with ulcerative colitis by incubating mucosa with tritiated thymidine in vitro and processing for autoradiography. We found that patients with ulcerative colitis in remission showed a proliferative pattern similar to that seen in both regenerating and "precancerous' mucosa. Patients with a short history were as likely to show this pattern as those with a long history, and this shows that the abnormal pattern does not signify impending malignant change. We also found that mucosa from patients with ulcerative colitis in remission showed an increased proportion of cells synthesising DNA, a proportion surprisingly close to that seen in an active phase; this suggests that the abnormal pattern seen in remission is the pattern of a regenerating mucosa. We feel that this high rate of mucosal turnover, sustained not just during clinically active disease but throughout remission, leads to the increased incidence of carcinoma and to the development of carcinoma in flat mucosa.

Electrical arrhythmias in the human stomach.

Abstract: Myoelectrical activity was recorded from the human antrum on 136 occasions using a monopolar mucosal electrode in preoperative and post-vagotomy patients, and bipolar serosal electrodes in post-cholecystectomy patients, and the incidence of antral arrhythmias observed. Arrhythmias of long duration were observed in five out of 62 patients after vagotomy and one out of 10 patients after cholecystectomy, but not in preoperative patients. They were characterised by slow waves with increased frequency, variable period, amplitude, and wave shape and were associated with periods of slow wave inhibition. None of the patients with an arrhythmia had any symptoms of disordered gastric motility. Antral arrhythmias could also be induced in some patients by the administration of insulin, secretin, cholecystokinin-pancreozymin, glucagon, and pentagastrin. The appearance of antral arrhythmias is probably due to a relative increase of sympathetic over parasympathetic activity. The maximal slow wave frequency observed was 8.3 cycles per minute and it is probable that in vivo human antral smooth muscle has a maximum frequency above which it cannot be driven.

Is mitochondrial antibody diagnostic of primary biliary cirrhosis

Abstract: In a series of 218 patients diagnosed as having primary biliary cirrhosis only nine exhibited a negative serum mitochondrial antibody. On examining additional specimens from these patients, seven were found to be positive, giving a final incidence of greater than 99%. The two patients whose sera remained negative for the mitochondrial antibody had liver histology compatible with the diagnosis of primary biliary cirrhosis, but a firm diagnosis could not be reached. Three additional mitochondrial antibody positive subjects who were asymptomatic and exhibited normal serum alkaline phosphatase were shown on liver biopsy to have stage I primary biliary cirrhosis. The presence of a positive serum mitochondrial antibody in a patient with or without abnormalities in liver function tests strongly suggests the diagnosis of primary biliary cirrhosis.

Adenomatous residue in cancerous papilla of Vater.

Abstract: Surgical specimens of carcinoma in the papilla of Vater were studied histologically Adenomatous residue which suggested that the carcinoma was derived from a pre-existing adenoma was found in 18 cases (818%) out of 22 The histological transition of adenoma into carcinoma was also frequently seen

Pregnancy and liver disease.

Abstract: The concurrence of pregnancy and liver disease is uncommon, and in most cases no alteration in the management of either condition is required. Occasionally, liver disease specific to pregnancy occurs or a patient known to have liver disease becomes pregnant and special consideration must be given to the fetus and the maternal liver disease. The diagnosis and management of liver disease in the pregnant patient has not been considered unless it is specifically altered on account of the pregnancy, and in these cases reference to standard textbooks will be found useful.1-3 The changes in liver function which occur during normal pregnancy have been well reviewed4-6 and are summarised in the Table. Hepatic blood flow is not increased during pregnancy, and a smaller proportion of the cardiac output, which is increased during pregnancy, passes to the liver. Histological examination of liver biopsy specimens from normal pregnant patients show no significant abnormalities.6 7

Electrochemical detector for breath hydrogen determination: measurement of small bowel transit time in normal subjects and patients with the irritable bowel syndrome.

Abstract: A method is described for the measurement of hydrogen in expired air, using an electrochemical detector. The apparatus is simple to use and sensitive. Its application is illustrated by studies of small bowel transit time made by measuring the time between oral ingestion of the unabsorbable carbohydrate lactulose and a rise in the concentration of hydrogen in expired air. In 20 control subjects transit time was 93.0 +/- 6.6 minutes, while in 16 patients with diarrhoea due to the irritable bowel syndrome it was 54.1 +/- 6.3 minutes (P less than 0.001), suggesting an abnormality in small intestinal motility in these patients. Loperamide, a potent antidiarrhoeal agent, increased transit time in 12 of these patients from 56.3 +/- 6.7 to 100.0 +/- 10.2 minutes (P less than 0.001).

Acute gastric dilatation with infarction and perforation Report of fatal outcome in patient with anorexia nervosa

Abstract: This is a report of a 22-year-old woman with treated anorexia nervosa who died of complications of acute gastric dilatation—that is, infarction and perforation with severe and irreversible shock. Binge eating and drinking, precipitated by emotional crises, contributed to her acute gastric dilatation. This complication of anorexia nervosa has been previously reported, but, unlike the others, this case ended fatally. The literature is reviewed.

Loperamide: studies on its mechanism of action.

Abstract: The effects of loperamide on net solute and water absorption, and prostaglandin E2 (PGE2) and cholera toxin-induced secretion were studied in the rat jejunum using an in vivo steady-state perfusion technique. Loperamide stimulated absorption of fluid, electrolytes, and glucose and reversed PGE2 and cholera toxin-induced secretion to absorption; this opiate analogue had no effect on cholera toxin stimulation of adenylate cyclase activity or the rise of tissue cyclic AMP (cAMP) concentrations. The opiate antagonist, naloxone, reduced the antisecretory effects of loperamide without affecting tissue levels of cAMP. These results indicate that loperamide inhibits PGE2 and cholera toxin-induced secretion, and that this phenomenon is independent of any direct effect that cholera toxin has on the adenylate cyclase system. The action of naloxone suggests, but does not prove, that loperamide exerts its effect via opiate receptors.

Release of vasoactive intestinal polypeptide from the cat small intestine exposed to cholera toxin.

Abstract: During a four hour observation period vasoactive intestinal polypeptide (VIP) is released in increasing amounts from the feline small intestine exposed to cholera toxin. As VIP is known to be located almost exclusively in the intestinal nerves, the present findings strongly suggest that cholera toxin activates the enteric nervous system. The findings of this and other studies performed in this laboratory lead to the proposal that the choleraic secretion is, at least in part, secondary to the activation of intramural nervous reflexes in the gut.

Prospective evaluation of the diagnostic accuracy of liver ultrasonography.

Abstract: Liver ultrasound was prospectively evaluated in 104 subjects who underwent liver biopsy, including 24 patients without evidence of liver disease (controls), and 80 with a broad spectrum of liver pathology. Ultrasonography was very specific (100%) and moderately sensitive (70%) in the detection of liver pathology, and hepatic neoplasms, steatosis, and fibrosis were detected by ultrasound in 80%, 80%, and 67% of cases respectively. In addition, ultrasonography diagnosed other pathologies--mainly biliary tract disease and abdominal neoplasms--in 26% of the patients.

Manometric evaluation of rectal prolapse and faecal incontinence.

Abstract: Sixty-three patients with complete rectal prolapse and/or faecal incontinence have undergone anal manometry and the results have been compared with an equal number of age- and sex-matched controls. Maximal basal pressure (MBP) and maximum squeeze pressure (MSP) were measured before and at four months and a year after treatment. The anal pressures of normal subjects are presented. Patients with rectal prolapse alone had normal anal pressures, whereas patients with incontinence with or without prolapse had significantly lower basal and squeeze pressures than controls. Successful surgical treatment of prolapse or incontinence did not produce significant change in anal canal pressures, whereas the combination of pelvic floor exercises and a continence aid was associated with a significant rise in MSP.

Double contrast enema and colonoscopy in polyp detection.

Abstract: The diagnostic accuracy of double contrast enema was assessed by colonoscopy of 250 consecutive patients with polypoid lesions that were observed at double contrast enema. The enema method detected 90% of all existing polypoid lesions, and gave false positive results in less than 3.5% Colonoscopy revealed 91% of the lesions. Double contrast enema is suitable as a screening procedure and, when used in combination with colonoscopy, only very few polyps will escape detection. The large number of neoplastic polyps detected in this retrospective series emphasises the necessity for a careful radiographic technique combined with colonoscopy to disclose and treat these potentially malignant lesions of the colon.

Role of mucosal prostaglandins and DNA synthesis in gastric cytoprotection by luminal epidermal growth factor.

Abstract: This study compares the effect of epidermal growth factor and prostaglandins (PGE2 or PGI2), applied topically to gastric mucosa, on gastric secretion and formation of ASA-induced gastric ulcerations in rats Epidermal growth factor given topically in non-antisecretory doses prevented dose-dependently the formation of ASA-induced ulcers without affecting prostaglandin generation but with a significant rise in DNA synthesis in the oxyntic mucosa The anti-ulcer effect of topical prostaglandins was also accompanied by an increase in DNA synthesis This study indicates that topical epidermal growth factor, like PGE2 or PGI2, is cytoprotective and that this cytoprotection is not mediated by the inhibition of gastric secretion or prostaglandin formation but related to the increase in DNA synthesis in oxyntic mucosa

Distribution of prostaglandins in gastric and duodenal mucosa of healthy subjects and duodenal ulcer patients: effects of aspirin and paracetamol.

Abstract: The distribution of mucosal PGE2-like activity was determined by bioassay technique in the body and antrum of the stomach and in the duodenum of healthy subjects and duodenal ulcer patients before and after administration of aspirin, paracetamol, or histamine. In healthy subjects, the oxyntic, antral and duodenal mucosa was found to be capable of generating large amounts of PGE2, which were not significantly different from those found in duodenal ulcer patients. No correlation was found between the generation of PGE2 and gastric acid secretory status or serum gastrin level. Aspirin-and to a much lesser extent, paracetamol-caused a dramatic reduction in the ability of the gastric mucosa to biosynthesis PGE2 and this was accompanied by marked side-effects and injury to the gastric mucosa. Administration of histamine caused small but significant reduction in the biosynthesis of PGE2 but it was accompanied by marked mucosal damage. This study indicates that the gastric and duodenal mucosa is capable of generating PGE2-like activity which may be involved in the mechanism that protects the mucosa against the damage caused by aspirin.

Inhibition of leucocyte motility by drugs used in ulcerative colitis.

Abstract: The effects on leucocyte motility of sulphasalazine (Salazopyrin) and its metabolites sulphapyridine and 5 amino-salicylic acid have been compared with those of prednisolone and indomethacin. Sulphasalazine, its active metabolite 5 amino-salicylic acid, and prednisolone are all potent inhibitors of leucocyte motility. Sulphapyridine and indomethacin are non-inhibitory. Inhibition of leucocyte motility may explain why sulphasalazine and 5 amino-salicylic acid are effective in ulcerative colitis while sulphapyridine is not. The lack of effect of indomethacin suggests that this action of sulphasalazine does not involve inhibition of prostaglandin synthesis.

Response of the intestinal mucosa to ischaemia.

Abstract: The small intestinal mucosa is particularly sensitive to ischaemia, but it also possesses a tremendous regenerative potential. The mucosa of the colon is less easily destroyed by a reduction in the blood supply, but, once damaged, it recovers imore slowly. In these pages we shall review the various structural and functional studies, performed in experimental animals, that have contributed to our understanding of the response of these epithelia to dfifferent degrees of ischaemia.