Arginine and ornithine are precursors of nitric oxide and polyamines, respectively. These metabolites intimately participate in permeability and adaptive responses of the gut. The liver possesses high arginase activity as an intrinsic part of urea synthesis and would consume most of the portal supply of dietary arginine. The gut reduces this possibility by converting dietary arginine to citrulline, which effectively bypass the liver and is resynthesized to arginine in the kidney. Dietary ornithine supplementation, in the form of ornithine alpha-ketoglutarate (OKG) can be considered as an arginine precursor. Several supplement studies have shown both amino acids to promote growth hormone and insulin secretion with anabolic effects in postoperative patients. Their intermediary metabolites (for example, glutamine, proline) may also be of benefit in trauma metabolism. Specific effects of either amino acid on the gut are poorly reported. One recent animal study showed improved morphology after OKG administration, perhaps through increased polyamine secretion. Generation of nitric oxide from arginine has two facets. Excess production from high dose arginine potentiated the effects of experimentally induced sepsis, whereas low doses improved survival. These considerations suggest that the role of enteral diet supplementation with arginine or OKG should be urgently examined for any benefits it may have on mucosal barrier function.

The gastrointestinal tract, besides being the organ responsible for nutrient absorption, is also a metabolic and immunological system, functioning as an effective barrier against endotoxin and bacteria in the intestinal lumen. The passage of viable bacteria from the gastrointestinal tract through the epithelial mucosa is called bacterial translocation. Equally important may be the passage of bacterial endotoxin through the mucosal barrier. This article reviews the evidence that translocation of both endotoxin and bacteria is of clinical significance. It summarises recent published works indicating that translocation of endotoxin in minute amounts is a physiological important phenomenon to boost the reticuloendothelial system (RES), especially the Kupffer cells, in the liver. Breakdown of both the mucosal barrier and the RES capacity results in systemic endotoxaemia. Systemic endotoxaemia results in organ dysfunction, impairs the mucosal barrier, the clotting system, the immune system, and depresses Kupffer cell function. If natural defence mechanisms such as lipopolysaccharide binding protein, high density lipoprotein, in combination with the RES, do not respond properly, dysfunction of the gut barrier results in bacterial translocation. Extensive work on bacterial translocation has been performed in animal models and occurs notably in haemorrhagic shock, thermal injury, protein malnutrition, endotoxaemia, trauma, and intestinal obstruction. It is difficult to extrapolate these results to humans and its clinical significance is not clear. The available data show that the resultant infection remains important in the development of sepsis, especially in the critically ill patient. Uncontrolled infection is, however, neither necessary nor sufficient to account for the development of multiple organ failure. A more plausible sequelae is that bacterial translocation is a later phenomenon of multiple organ failure, and not its initiator. It is hypothesized that multiple organ failure is more probably triggered by the combination of tissue damage and systemic endotoxaemia. Endotoxaemia, as seen in trauma patients especially during the first 24 hours, in combination with tissue elicits a systemic inflammation, called Schwartzmann reaction. Interferon gamma, a T cell produced cytokine, is thought to play a pivotal part in the pathogenesis of this reaction. This reaction might occur only if the endotoxin induced cytokines like tumour necrosis factor and interleukin 1, act on target cells prepared by interferon gamma. After exposure to interferon gamma target cells become more sensitive to stimuli like endotoxin, thus boosting the inflammatory cycle. Clearly, following this line of reasoning, minor tissue damage or retroperitoneal haematoma combined with systemic endotoxaemia could elicit this reaction. The clinically observed failure of multiple organ systems might thus be explained by the interaction of tissue necrosis and high concentrations of endotoxin because of translocation. Future therapeutic strategies could therefore focus more on binding endotoxin in the gut before the triggering event, for example before major surgery. Such a strategy could be combined with the start of early enteral feeding, which has been shown in animal studies to have a beneficial effect on intestinal mucosal barrier function and in traumatized patients to reduce the incidence of septic complications.

Damage to the mucosal barrier may be assessed, non-invasively by use of sugar probes, which permeate through the transcellular or paracellular (tight junction) routes. A standardised test, with analysis of a five hour urine collection has proved useful in studying the sequelae of non-steroid anti-inflammatory drug (NSAID) administration, untreated coeliac disease, and enteric infections. Choice of probe molecule is crucial and lactulose/l-rhamnose seem to be satisfactory, in contrast with polyethylene glycol. Significant correlations have been seen between permeability and plasma IgA concentrates in nephropathy, and between permeability and the passage of neutrophil chemotactic agents. The increased permeability associated with NSAID treatment may relate to the adverse effects of NSAIDs on enterocyte mitochondrial morphology and metabolism. These two factors may predispose the mucosa to permeation of bacterial chemoattractant molecules that elaborate a local inflammatory response. A similar mechanism may operate in patients with untreated Crohn's disease, who show abnormally high permeability. Remission induced by treatment with elemental diets coincides with a reduction in permeability. The period to relapse correlated with the inability of patients to maintain low permeability to sugar probes. These results suggest a mechanism for the benefits of elemental enteral nutrients in the treatment of Crohn's disease.

Diet is of fundamental importance in the healthy functioning of alimentary epithelium, or during the disease process. Specifically, the incidence of 'non-hereditary' gastrointestinal disease varies widely throughout the world, partly because of different cultural and dietary habits. The aim of this review is to outline the mechanisms that modulate normal mucosal development and growth in the small and large intestine. In addition a brief mention will be made of morphological changes in certain pathological conditions.

Morbidity and mortality related to pancreatic surgery are still high: 30-40% and 3-10% respectively. As most complications are probably related to exocrine pancreatic secretion, its inhibition could improve the postoperative course. In 1979, Klempa saw a low complication rate after Whipple resection in a small number of patients treated with somatostatin, a powerful inhibitor of pancreatic exocrine secretion. The long acting somatostatin analogue, octreotide, also inhibits pancreatic exocrine secretion and can be given by subcutaneous injections. Two double blind, placebo controlled, multicentre studies with randomisation into parallel groups were recently performed to find out if peri and postoperative administration of octreotide (100 micrograms thrice daily subcutaneously) reduces the rate of complications specifically related to pancreatic surgery. Both trials consistently showed that octreotide can reduce substantially (over 40%) the risk of complications in these patients; the treatment acceptability was good.

Acute pancreatitis is caused by the activation of digestive enzymes in the pancreas and a possible treatment, therefore, is the inhibition of enzyme secretion. This approach is somewhat controversial, however, as it is not clear whether pancreatic secretion continues to occur during the course of acute pancreatitis. Animal studies show an appreciable reduction of secretion in the inflamed pancreas, but studies in humans are not conclusive. The use of somatostatin or its analogue, octreotide, has been investigated in several clinical studies. A meta analysis of six individual studies in which somatostatin was given for acute pancreatitis showed that somatostatin significantly reduces mortality. A trial in patients with moderate to severe acute pancreatitis showed a lower rate (although not statistically significant) of complications in patients treated with 3 x 200 and 3 x 500 micrograms/day octreotide, compared with controls and patients receiving a lower dose of octreotide. A further study showed a significant reduction in patient controlled analgesics in patients treated with octreotide compared with controls. Pain is the important clinical symptom of chronic pancreatitis, possibly resulting from an increased intraductal pressure during secretion. The effect on pain of the inhibition of pancreatic secretion by octreotide has been investigated in two studies. One showed no significant reduction in pain after treatment with octreotide for three days. In the other, in which octreotide was used for three weeks, significantly less pain and analgesic use was recorded during octreotide treatment than during placebo. The most common complication of chronic pancreatitis is the formation of pseudocysts. There is some evidence that octreotide may be useful in their treatment.

Somatostatin is a 14 amino acid peptide that inhibits pancreatic exocrine and endocrine secretion. Its clinical application has been limited by its very short half life, necessitating continuous intravenous infusion. Octreotide is an 8 amino acid synthetic analogue of somatostatin that possesses similar pharmacological effects. It has a much longer duration of action, however, and can be given subcutaneously. Both the intravenous and subcutaneous routes of injection of octreotide are well tolerated. Peak serum concentrations occur within 30 minutes after subcutaneous administration and within four minutes of a three minute intravenous infusion. Serum concentration increases linearly with dose. Octreotide is distributed rapidly, mainly in the plasma, where it is 65% protein bound. The elimination half life is about 1.5 hours and about 32% of a subcutaneous dose is excreted in the urine as unchanged octreotide. Octreotide inhibits gastroenteropancreatic secretion, especially of insulin, glucagon, pancreatic polypeptide, gastric inhibitory polypeptide, and gastrin. It also inhibits both release of thyroid stimulating hormone and growth hormone secretion in response to exercise, insulin induced hypoglycaemia, and argenine stimulation. Octreotide reduces splanchnic blood flow in healthy volunteers and hepatic venous pressure in cirrhotic patients. It can accelerate or delay gastric emptying, prolong transit time at moderate to high doses, stimulate motility at low doses, and inhibit gall bladder emptying. Octreotide considerably inhibits pentagastrin stimulated gastric acid secretion and significantly diminishes exocrine pancreatic function (amylase, trypsin, lipase). Octreotide increases intestinal transit time and decreases endogenous fluid secretion in the jejunum and ileum, thus increasing the absorption of water and electrolytes. These pharmacological effects of the analogue point to its therapeutic role in a variety of endocrine and gastrointestinal disorders.

Summary of main recommendations(1) Glutaraldehyde, used in most endoscopy units in the United Kingdom for the disinfection of flexible gastrointestinal endoscopes, is a toxic substance being an irritant and a sensitiser; symptoms associated with glutaraldehyde exposure are common among staff working in endoscopy units.(2) The Control of Substances Hazardous to Health Regulations 1988 (COSHH) obliges the employer to make a systematic assessment of risk to staff of exposure to glutaraldehyde and institute measures to deal effectively with exposure.(3) At present glutaraldehyde remains the first line agent for the disinfection of flexible gastrointestinal endoscopes. Other agents are being developed; a standard means of assessment for flexible endoscope disinfectants should be devised.(4) Equipment and accessories that are heat stable should be sterilised by autoclaving; disposable accessories should be used wherever possible.(5) Flexible gastrointestinal endoscopes should be disinfected within automated washer/disinfectors; trays, bowls or buckets for this purpose are unacceptable.(6) Local exhaust ventilation must be used to control glutaraldehyde vapour. Extracted air may be discharged direct to the atmosphere or passed over special absorbent filters and recirculated. Such control measures must be regularly tested and records retained.(7) Endoscope cleaning and disinfection should be carried out in a room dedicated to the purpose, equipped with control measures to maintain the concentration of glutaraldehyde vapour at a level certainly below the current occupational exposure standard of 0.2 ppm and preferably below the commonly used working limit of 0.1 ppm. Sites other than the endoscopy unit where endoscopy is regularly performed, such as the radiology department, should have their own fully equipped cleaning and disinfection room.(8) COSHH limits the use of personal protective equipment to those situations where other measures cannot adequately control exposure. Such equipment includes nitrile rubber gloves, apron, chemical grade eye protection, and respiratory protective equipment for organic vapours.(9) Monitoring of atmospheric levels of glutaraldehyde should be performed by a competent person such as an occupational hygienist; the currently preferred method of sampling uses a filtration technique, the commercially available meters being less reliable.(10) Health surveillance of staff is mandatory; occupational health records must be retained for 30 years.(11) Endoscopy staff must be informed of the risks of exposure to glutaraldehyde and trained in safe methods of its control. Only staff who have completed such an education and training programme should be allowed to disinfect endoscopes.(12) The unsafe use of glutaraldehyde has significant health and legal consequences; the safe use of glutaraldehyde may have revenue consequences that contribute significantly to the cost of gastrointestinal endoscopy.

Somatostatin was first suggested for the treatment of acute pancreatitis more than 15 years ago but despite many studies, its role in the management of this condition remains unclear. The experimental and clinical studies are reviewed and the physiological actions of somatostatin, which may influence the course of acute pancreatitis are examined. It is concluded that although some reports suggest a trend towards improved survival and lessened complication rate with somatostatin treatment, insufficient evidence of benefit exists to support the use of somatostatin or its analogue in the treatment or prophylaxis against acute pancreatitis in routine clinical practice.

This paper reports on two patients with carcinoid tumours of the gall bladder who presented to the Aberdeen hospitals during the period 1970 to 1990 and reviews all previously reported cases in published works.

Coagulopathy is a well recognised complication of peritoneovenous shunting for ascites. The relative contributions of primary fibrinolysis and disseminated intravascular coagulation remain controversial. Plasminogen activating activity was significantly lower in malignant ascites (n = 10, median < 0.02 (range < 0.02-1.26) IU/ml) than in alcoholic ascites (n = 10, 1.07 (0.30-1.49) IU/ml) (p < 0.05). Fibrinolytic activity was determined by a balance between tissue plasminogen activator and plasminogen activator inhibitor-1. There was no significant difference between the two groups in the concentration of tissue plasminogen activator (34 (12-64) ng/ml in malignant ascites v 29 (12-43) ng/ml in alcoholic ascites), but the concentration of plasminogen activator inhibitor-1 was significantly higher in malignant ascites (736 (213-1651) ng/ml) than in alcohol ascites (29 (12-43) ng/ml) (p < 0.05). Malignant ascites contained significantly higher concentrations of urokinase (0.7 (< 0.1-1.3) ng/ml v 0.2 (< 0.1-0.6) ng/ml in alcoholic ascites) and plasminogen activator inhibitor-2 (33 (< 6-140) ng/ml v 9 (< 6-28) ng/ml alcoholic ascites). The plasminogen activating activity of alcohol ascites may lead to primary fibrinolysis after peritoneovenous shunting. The considerably lower activity found in malignant ascites may explain why coagulopathy after shunting is less pronounced in this group of patients.

A prospective surveillance programme for patients with longstanding (> = 8 years), extensive (> = splenic flexure) ulcerative colitis was undertaken between 1978 and 1990. It comprised annual colonoscopy with pancolonic biopsy. One hundred and sixty patients were entered into the programme and had 739 colonoscopies (4.6 colonoscopies per patient; 709 patient years follow up). Eight eight per cent of examinations reached the right colon. There was no procedure related death. One Dukes's A cancer was detected. Forty one patients (25%) defaulted. Of these 25 remain well; 13 are unaccounted for, and one died from colonic cancer. One patient had colectomy for medical reasons, and another died of carcinoma of the pancreas. Retrospectively an additional 16 eligible patients were identified who had not been recruited. Of these, 14 remain well, two are unaccounted for. None developed colonic cancer. Four patients refused colonoscopy. All remain well. Over the same period seven other cases of colonic cancer were found in association with ulcerative colitis, two in patients who had erroneously been diagnosed as having only proctitis and were therefore not entered into the programme, but were found at operation to have total colitis, one in a patient with colitis of seven years duration, and four patients who had previously attended the clinic but had been lost to follow up before 1978 and then had represented with new symptoms during the surveillance period. Thus, of the nine colitis related cancers diagnosed in this centre during the study period only one was detected by the surveillance programme. The results of this large study, a a review of published works, cast doubts on the effectiveness of colonoscopic surveillance programmes in detecting colorectal cancer in patients with ulcerative colitis.

Primary oesophageal involvement by lymphoma in two patients, one with Hodgkin's disease and one with non-Hodgkin's lymphoma is reported. In both, there were no manifestations of the disease outside the oesophagus, which is exceptionally rare. In the patient with non-Hodgkin's lymphoma, the oesophageal tumour was the first manifestation of lymphoma. Shortly after admission he developed a tracheo-oesophageal fistula from which he died before treatment could be started. In the patient with Hodgkin's disease, isolated oesophageal lymphoma was the first relapse after a 13 year interval free of disease. As he had previously received mediastinal irradiation he was treated with combination chemotherapy that resulted in long term survival (> five years). Several other long term survivors have been described but only after radiotherapy or surgery. These findings suggest that systemic chemotherapy may be equally successful in treating isolated primary oesophageal lymphoma, thus offering an alternative for those patients in whom local treatment is contraindicated.

The painful rib syndrome consists of three features: pain in the lower chest or upper abdomen, a tender spot on the costal margin, and reproduction of the pain on pressing the tender spot. This is a common cause for referral to a general medical/gastroenterology clinic, accounting for 3% of new referrals in Lincoln. Seventy six consecutive patients were studied. The mean age was 48 years and 70% were women. Forty three per cent had been investigated, often extensively, before referral, and eight had had a non-curative cholecystectomy. The case notes from all patients were reviewed and a follow up questionnaire was sent after a mean period of four years to those 72 still alive, of which 56 replied. Thirty nine (70%) still had the pain although all except three had learnt to live with it. Despite a firm diagnosis being given, 25 (33%) patients were referred again to hospital by their general practitioner. All further investigations were negative apart from the finding of gall stones in three patients. The four patients who died had died from unrelated causes. The painful rib syndrome is common but underdiagnosed. It is a safe, clinical diagnosis requiring no investigation. Systematic firm palpation of the costal margin in recommended in all patients presenting with pain in the lower chest or upper abdomen.

A 14 year old girl with multiseptate gall bladder and cystic dilatation of the biliary tree is presented. This is the 20th published case report of patients with multiseptate gall bladder and only the second to be associated with a choledochal cyst. The cystic spaces of the gall bladder did not communicate with the neck of the gall bladder or the rest of the biliary tree, and this unusual feature has not been previously described. A multiseptate gall bladder with a normal biliary tree commonly causes symptoms suggestive of cholecystitis, although gall stones are seldom present. Diagnosis is confirmed by an oral cholecystogram or ultrasound scan that may show the fine intraluminal septae, and these features should be looked for in patients with biliary symptoms without biliary calculi. Cholecystectomy is curative for the isolated gall bladder anomaly but hepaticojejunostomy may be necessary for an associated choledochal cyst.

The secretory response of gastric acid to pure ethanol and alcoholic beverages may be different because the action of the non-ethanolic contents of the beverage may overwhelm that of ethanol. Pure ethanol in low concentrations (< 5% vol/vol) is a mild stimulant of acid secretion whereas at higher concentrations it has either no effect or a mildly inhibitory one. Pure ethanol given by any route does not cause release of gastrin in humans. Alcoholic beverages with low ethanol content (beer and wine) are strong stimulants of gastric acid secretion and gastrin release, the effect of beer being equal to the maximal acid output. Beverages with a higher ethanol content (whisky, gin, cognac) do not stimulate gastric acid secretion or release of gastrin. The powerful stimulants of gastric acid secretion present in beer, which are yet to be identified, are thermostable and anionic polar substances. The effect of chronic alcohol abuse on gastric acid secretion is not as predictable. Chronic alcoholic patients may have normal, enhanced, or diminished acid secretory capacity; hypochlorhydria being associated histologically with atrophic gastritis. There are no studies on the acute effect of alcohol intake on gastric acid secretion in chronic alcoholic patients. The acid stimulatory component of beer and wine needs to be characterised and its possible role in the causation of alcohol induced gastrointestinal diseases needs to be investigated.

An elderly woman with chronic ulcerative colitis who developed proximal muscle weakness, increased serum creatine phosphokinase activity, and histological and electromyographic abnormalities characteristic of polymyositis is described. Treatment with corticosteroids and 5-acetylsalicylic acid was followed by a remission in bowel symptoms, improvement in muscle power, and reversal of electromyographic changes. An autoimmune link between the two disorders seems likely.