In vitro behavior of human intestinal mucosa. The influence of acetyl choline on ion transport.

The possibility that the autonomic nervous system may influence the function of intestinal mucosa was investigated by assessing the effect of acetyl choline on ion transport in human intestine. Isolated pieces of stripped ileal mucosa were mounted in Perspex flux-chambers and bathed in isotonic glucose Ringer's solution. Acetyl choline caused a rise in mean potential difference (8.8-12.3 mV, P less than 0.002) and short circuit current (287.7-417.2 muA-cm-2, P less than 0.01) (n = 12), observable at a concentration of 0.01 mM and maximal at 0.1 mM. This effect was enhanced by neostigmine and blocked by atropine. Isotopic flux determinations revealed a change from a small mean net Cl absorption (58) to a net Cl secretion (-4.3mueq-cm-2-h-1P less than 0.001) due predominantly to an increase in the serosal to mucosal unidirectional flux of Cl (10.63-14.35 mueq-cm-2-h-1P less than 0.05) and a smaller reduction in the mucosal to serosal flux (11.22 to 10.02 mueq-cm-2-h-1P less than 0.05). Unidirectional and net Na transport was unaffected. A similar electrical and ion transport response was observed in a single study of two pieces of jejunal mucosa. In the absence of glucose net chloride secretion was produced and again an insignificant effect on net sodium transport was noted. Acetyl choline did not provoke a sustained effect on mucosal cyclic adenine nucleotide levels although a short-lived cyclic adenine nucleotide response was seen in some tissues 20-30 s after drug addition. These studies demonstrate that acetyl choline does influence human intestinal ion transport by stimulating chloride secretion and suggest a possible mechanism by which the parasympathetic nervous system could be concerned in the control of ion transport.

A lethal complication of peripheral vein vasopressin infusion.

A patient bleeding from oesophageal varices in whom injection sclerotherapy failed to control bleeding required peripheral vein vasopressin infusion for a total of five days. Three days after stopping the infusion she collapsed and died. Post mortem examination showed the cause of death to be intestinal infarction resulting from superior mesenteric and portal vein thrombosis. This complication has not previously been described in association with vasopressin infusion into peripheral veins. The duration of each infusion should be minimised and blood volume should be carefully monitored throughout. The condition should be suspected in patients who develop unexplained abdominal pain or collapse following vasopressin treatment.

The therapeutic dilatation of enteric strictures due to Crohn's disease.

The use of dilatation as a treatment of strictures due to Crohn's disease has hitherto received little attention. We report dilatation of small and large bowel strictures in twelve patients with Crohn's disease. The technique appears to be safe when carried out either endoscopically or as part of a laparotomy. Short term follow-up suggests that the technique may have a part to play in the treatment of suitable strictures that can be reached endoscopically but early restenosis limits its value at laparotomy when strictureplasty may provide a more lasting relief of the stenosis.

The importance of laparotomy in the diagnosis and management of intestinal bleeding of obscure origin.

Thirty-seven patients who had had either a colonoscopy or a selective mesenteric angiogram while being investigated for severe or persistent gastrointestinal bleeding of obscure origin were reviewed. Failure to make a prompt diagnosis was partly responsible for the 16% hospital mortality in the series. Colonoscopy was diagnostic on 6 out of 38 examinations but detected 43% of lesions in the colon. Angiography achieved only 3 diagnoses in 17 examinations. Fourteen patients had an exploratory laparotomy which was diagnostic in 9. We believe that early laparotomy still has an important place in the diagnosis and treatment of intestinal bleeding of obscure origin.

Mechanisms of transport of Na, Cl, and K in the human colon.

Ionic transport across isolated, stripped, human colonic mucosa was studied in vitro using a modified short circuit current technique. Electrical potential difference and short circuit current were dependent on the presence of sodium ions in the mucosal bathing solution and were unaffected by addition of 10 mM glucose to the solution. Ouabain (10(-3) M) added to the serosal reservoir abolished both potential difference and short circuit current. Isotopic flux measurements across short-circuited colonic mucosa showed a net active sodium absorption which accounted for the observed short circuit current and was unaffected by 10 mM glucose. Chloride was also actively absorbed and this was unaffected by removal of sodium from the bathing solutions. Ouabain abolished net sodium absorption but had no effect on chloride absorption. There was a net active secretion of potassium which was abolished in sodium-free buffer. We conclude that sodium is actively absorbed via a rheogenic process which is not stimulated by glucose; chloride is actively absorbed via a nonelectrogenic process, not linked to sodium transport, and probably involving a Cl-HCO3- exchange; and postassium is actively secreted possibly via a Na+K+ exchange.

Electrolyte transport across colonic mucosa from patients with inflammatory bowel disease.

To investigate the pathogenesis of diarrhea in inflammatory bowel disease, electrolyte transport was examined in vitro in stripped colonic mucosa taken from the sigmoid or descending colon in colectomy specimens. Compared with previously reported values from normal colon, the electrical potential difference, short circuit current, and mucosal resistance were significantly lower in diseased mucosa. This reduction was associated with a significantly lower net sodium absorption in diseased mucosa, owing to a reduced mucosa to serosa unidirectional flux. Net chloride flux was similar to normal, but unidirectional fluxes were reduced. In mucosa from patients treated with corticosteroids, fluxes were similar to normal, while in untreated patients they were markedly impaired. It is concluded that there is a defect in active sodium absorption in inflammatory bowel disease that may contribute to the diarrhea. A secretory process, inhibited by sulphasalazine, cannot be excluded however.

Prediction of mortality at endoscopy in bleeding peptic ulcer disease.

One hundred and forty two patients with bleeding peptic ulcers underwent emergency endoscopy. Seventy six had endoscopic stigmata of haemorrhage and nine subsequently died. There were no deaths amongst sixty six patients without stigmata (p less than 0.02). Patients with stigmata were also significantly more likely to experience further bleeding (p less than 0.001) and to require emergency operations (p less than 0.01). Excess risk attached to those with bleeding at the time of endoscopy and those with visible vessels or clot adherent to the ulcer but not to patients with staining of the ulcer base. Patients without stigmata or with staining alone should be managed conservatively. Clinical trials in bleeding peptic ulcer disease should only include patients in the high risk group.

Selection of patients for surgery following peptic ulcer haemorrhage.

Surgery remains the only widely available and well-proven means of stopping haemorrhage from peptic ulcers and preventing its recurrence but carries an unavoidable morbidity. If surgery is to be used to maximum effect with minimum morbidity, an accurate means of predicting which patients will suffer further haemorrhage is needed. Although over 80 per cent of patients who rebleed have the endoscopic stigmata of haemorrhage, a policy of operation in all patients with stigmata would lead to a very high operation rate and a high proportion of unnecessary operations, as one-half of the patients with stigmata do not rebleed. Clinical data were collected prospectively from 278 cases of peptic ulcer haemorrhage. The data from a randomly selected 75 per cent of the cases were analysed by stepwise logistical regression. Patients who had the endoscopic stigmata of haemorrhage and who had a probability of further haemorrhage, calculated from the regression equation, of more than 0.2 were identified as a high risk group. This definition was validated using the 25 per cent of cases not used in the initial analysis. Eighty-four per cent of patients in the high risk group suffered further haemorrhage and all such patients therefore require early surgery: such a policy would have resulted in an operation rate of 28 per cent. Thirty per cent of the patients who had further haemorrhage were not identified as being at high risk but none of them had a severe rebleed. The regression equation greatly enhanced the value of stigmata in guiding surgical decision making and merits further evaluation.

Per-endoscopic bipolar diathermy coagulation of visible vessels using a 3.2 mm probe--a randomised clinical trial.

Forty-four patients who had bled from peptic ulcers and whose ulcers showed stigmata of haemorrhage (bleeding, visible vessel or adherent clot) entered a trial of treatment with a 3.2 mm bipolar diathermy probe. Two patients had spurting haemorrhage when endoscoped and both were treated with the probe, control being obtained in one. The remaining patients were randomised to treatment or control groups. One patient who was treated was withdrawn because the ulcer proved to be malignant. Six of 20 treated patients rebled compared with 8 of 21 controls (relative risk 0.79; 90% CI 0.26-1.97). The operation rate, transfusion requirement and hospital stay were similar in the two groups. One perforation occurred in the treatment group. Per-endoscopic bipolar diathermy treatment confers little benefit in bleeding peptic ulcer disease.

Adenocarcinoma of the small intestine complicating Crohn's disease.

Adenocarcinoma of the small intestine is an uncommon complication of Crohn's disease. We report the clinical and pathological details of three cases diagnosed between 1968 and 1980 with a review of 58 cases from the literature. Of the 61 cases, 41 tumours occurred in the ileum, 18 in the jejunum, one in the duodenum and ileum, and one in the ileum and colon. Eighteen occurred in bypassed intestinal loops. The prognosis was poor: 44 patients (72%) had died with a mean interval of only 7.9 months from the diagnosis of cancer.

Study of ion transport across biopsies of ileostomy in vitro: search for evidence of intestinal 'adaptation' after colectomy.

To explore the possibility that small intestinal 'adaptation' may occur after colectomy we examined the ability of ileal mucosal biopsies, taken from patients with ileostomies, to transport electrolytes in vitro. Ileostomy mucosal electrical potential difference was higher (5.4+/-0.5 mV) than in normal mucosa (3.3+/-0.3, P less than 0.001), resistance was higher (98+/-12, against 40.3+/-2.8 omega cm-2), while short circuit current was lower (54.8+/-6.0; against 89.9+/-6.1 muA.cm-2). Net sodium absorption, 1.25+/-0.41 mumol.cm-2.h-1 (n=6), rose on addition of glucose (15 mM.1-1) to 11.57+/-0.8 mumol.cm-2.h-1 (n=4), and these were similar to results from normal ileum. Net chloride transport was also similar to noraml. In one subject, with intermittent ileostomy diarrhoea, net sodium absorption was normal, 2.14 mumol.cm-2.h-1, but there was marked active chloride secretion, 14.03 mumol.cm-2.h-1. These studies do not provide any evidence of enhanced electrolyte absorption across ileal mucosa as a response to colectomy. Some cases of ileostomy diarrhoea may be due to active chloride secretion.

Management of enterocutaneous fistulae in Crohn's disease.

The outcome among 39 patients with enterocutaneous fistulae complicating Crohn's disease has been reviewed. The patients were considered in two groups: (1) no disease - all were early postoperative fistulae (n = 9); (2) active disease (i) without abscess formation (n = 16), (ii) with abscess formation (n = 14). Postoperative fistulae with no evidence of active Crohn's disease healed spontaneously. Fistulae in the presence of active disease did not heal even with prolonged medical management. The only effective treatment was excision of the diseased segment from which the fistulae arose and any distal obstruction. None of the fistulae closed surgically has recurred.

Intracellular electrolyte depletion in patients with ileostomies.

Fourteen apparently healthy patients with ileostomies were found to be depleted of total exchangeable sodium and potassium, but had normal serum electrolyte concentrations and normal extracellular fluid and total body water volumes. The low exchangeable sodium and potassiums were thus primarily due to depletion of the intracellular compartment. There was no evidence of renal or intestinal conservation of these ions and plasma aldosterone, renin activity, and prolactin concentrations were normal in most and only moderately raised in a few. This apparent lack of any hormonal compensatory change to the electrolyte depletion may be due to the normality of the extracellular fluid volume and electrolyte concentrations. These patients seem to have adapted to a stable but depleted intracellular sodium and potassium state.

Colonic Crohn's disease and use of oral contraception.

The prevalence of use of oral contraception before the onset of disease was established in 100 consecutive women attending follow up clinics for inflammatory bowel disease. A significant excess of women with Crohn's disease confined to the colon had taken oral contraceptives in the year before developing symptoms (10/16 (63%] compared with women with small-intestinal Crohn's disease (12/49 (24%); p less than 0.02) and women with ulcerative colitis (3/35 (9%); p less than 0.0005). When the patient groups were matched for age and year of onset of disease usage of oral contraception before the onset of disease was still more common among women with isolated colonic Crohn's disease (9/12, 75%) than among those with ulcerative colitis (2/12 (17%); p less than 0.02) and was also more common than would be expected from reported figures for oral contraception in England and Wales (31.4% of women aged under 41; p less than 0.005). A survey of current patient records showed that isolated colonic disease was at least twice as common among women with Crohn's disease (63/218, 29%) compared with men (25/181, 14%; p less than 0.001). These data support the suggestion made previously that oral contraceptives may predispose to a colitis that resembles colonic Crohn's disease.

Optimal timing of operation for bleeding peptic ulcer: prospective randomised trial.

From October 1980 to September 1983 all patients with upper gastrointestinal bleeding were admitted to a centralised unit and investigated by early endoscopy. A total of 142 patients with a proved duodenal or gastric ulcer were randomised after stratification for age and site of ulcer to early (aggressive) surgical management or a delayed (conservative) policy. Significantly more operations (n = 42; 60%) were performed in the early than in the delayed (n = 9; 20%) groups (p less than 0.01). There were no deaths among the 42 patients under 60. The overall mortality in the 100 patients aged over 60 was 10% and when analysed on an "intention to treat" basis there was no difference between early and delayed surgery. When, however, an unrelated death from a bleeding colonic polyp was excluded and the data analysed on "treatment received" the mortality was only 2% in the early group compared with 13% in the delayed group (p less than 0.05). When analysis was confined to gastric ulcer the difference between early (0%) and delayed (24%) treatment was even greater. The results of this trial indicate that for patients over 60 an aggressive surgical policy is associated with a significant reduction in mortality.