The effect of prostaglandins, branched-chain amino acids and other drugs on the outcome of experimental acute porcine hepatic failure.

Prostaglandins, N-acetyl-cysteine, cholestyramine and essential phospholipids have all been shown to protect experimental animals from severe hepatic damage in various models when used prophylactically. Silibinin has been used in the treatment of Amanita phalloides poisoning. Branched-chain amino acids have been recommended in acute hepatic failure. We have used all these forms of therapy at the time of initiation of hepatic failure in a reliable pig model. Of the above, only prostaglandins have been shown to reverse the effects of the hepatic insult in terms of prolonged survival and histological changes. Although conventional liver function tests and plasma amino acids in prostaglandin-treated animals are not improved, cerebrospinal fluid amino acids remain normal, in contrast to the other groups of untreated and treated hepatic failure animals.

Antral gastrin concentrations in duodenal ulcer patients after cimetidine and highly selective vagotomy.

Post-prandial serum levels of gastrin, the main hormonal stimulator of acid secretion, have been shown to be significantly elevated after HSV compared with controls. The mechanism for this elevation is not known but could be secondary to an increased antral gastrin concentration (AGC). In this study AGCs were measured in endoscopic biopsies before and at intervals of 6 and 32 weeks after HSV in 12 patients with duodenal ulcer. Results were compared with 13 normal controls and 12 duodenal ulcer patients treated with cimetidine for 6 weeks. Blood was taken for fasting serum gastrin concentration at each endoscopy. In the HSV group AGC significantly increased on both postoperative occasions when compared with pre-operative values (P less than 0.01). AGC also showed a significant correlation with time after HSV (r = 0.71; P less than 0.01). Only one patient, who had a persistent duodenal ulcer, failed to show an increase in AGC. Cimetidine failed to increase AGCs in duodenal ulcer patients after 6 weeks of treatment. However, a subgroup (n = 7) of cimetidine-treated patients with low pretreatment AGCs, below 10 ng/mg, did show a significant rise at 6 weeks (P less than 0.05). Fasting serum gastrin levels did not change significantly in any of the three groups. It is concluded that HSV causes a significant increase in AGC with time.

Plasmaphoresis, charcoal, and resin perfusion in experimental porcine hepatic failure.

Acute hepatic failure was induced in pigs by a combination of phenobarbitone, reversible hepatic artery ischemia, and low-dose carbon tetrachloride. Plasmaphoresis combined with charcoal or resin plasma perfusion resulted in no significant reduction in arterial amino acid levels despite proven amino acid absorption by the charcoal columns. No prolongation of life was attained in the pigs when compared to nonplasmaphoresed control animals.

A predictable pathophysiological model of porcine hepatic failure.

A technique is described in which acute hepatic failure may be uniformly induced in pigs using a combination of oral phenobarbitone pretreatment and 2-hour interruption of hepatic arterial blood supply followed by intragastric carbon tetrachloride. This results in deep hepatic coma over a narrowly predictable time span and death within 12-52 h. Amino acid levels in plasma and cerebrospinal fluid obtained 24 h after the induction of hepatic failure were similar to those reported in human and experimental encephalopathy.

Amino acid absorption of plasmapheresed serum by resins and charcoal.

The amino acid absorption capacity of two types of charcoal and six forms of ion exchange resin has been assessed. To plasmapheresed serum obtained from human donors amino acids were added to stimulate the levels seen in hepatic failure. This was passed through columns of either resin or charcoal over three hours. The amino acid absorption was estimated. Charcoal consistently removed greater amounts of essential amino acids than resin. None of the ion exchange resins were found to be effective in amino acid absorption.

Treatment of chronic duodenal ulceration. Effectiveness of colloidal bismuth subcitrate tablets compared with cimetidine.

Fifty-eight patients with chronic duodenal ulceration proven at endoscopy consented to enter a trial comparing the effect of colloidal bismuth subcitrate (CBS)tablets with that of cimetidine. Fifty-four patients completed the six-week trial. An endoscopic assessment of healing was made at four weeks. If healing had not occurred, the trial was continued for another two weeks and the endoscopy was repeated. At four weeks, healing at endoscopy was demonstrated in 82% of patients receiving CBS and in 58% of those receiving cimetidine. At six weeks, the healing rates were 93% and 81%, respectively. No side effects were noted in either group. Continued smoking was not found to have an adverse effect on the healing rate of ulcers in either treatment group.

Colloidal bismuth subcitrate tablets and placebo in chronic duodenal ulceration: a double-blind, randomised trial.

In a double-blind, randomised trial of 46 outpatients with endoscopically proven chronic duodenal ulceration, 22 were given colloidal bismuth subcitrate (De-Nol, Gist-Brocades) and 24 were given placebo for four weeks. Clinical and laboratory assessment was made after two and four weeks' therapy. Endoscopic healing was demonstrated in 86.5% of patients taking colloidal bismuth tablets and in 25% of patients taking placebo. We observed no clinical or biochemical side effects in either group. These results indicate that colloidal bismuth subcitrate tablets are well tolerated, and are effective in healing chronic duodenal ulcers.

Metoclopramide. Management of gastrointestinal intolerance in rheumatoid arthritis patients.

Ten patients with rheumatoid arthritis who were unable to tolerate anti-inflammatory doses of non-steroidal anti-inflammatory drugs (NSAIDs) were admitted to the study. After endoscopy three patients were taken out of the study because of frank gastric ulceration. Seven patients entered the six-week study during which anti-inflammatory doses of NSAIDs were preceded by 30 minutes by a 10-mg dose of oral metoclopramide. The insults of this pilot study suggest that pretreatment with metoclopramide enables patients with rheumatoid arthritis who have non-ulcer dyspepsia to tolerate full dosage of NSAIDs.

Hepatocellular disease in the giant-cell arteritis/polymyalgia rheumatica syndrome.

An elderly man developed temporal arteritis and polymyalgia rheumatica with coexisting biochemical abnormalities of liver function. Biopsy revealed hepatic changes which have not been previously reported. There was hepatocellular necrosis and inflammation together with a prominent hyperplasia of perisinusoidal lipocytes of Ito. Temporal artery biopsy confirmed the presence of granulomatous panarteritis. Corticosteroid therapy produced rapid resolution of symptoms and reversion of liver function tests to normal.

The significance of widening of the presacral space at contrast radiography in inflammatory bowel disease.

The width of the presacral space was measured prospectively at various levels in 100 persons without organic colonic or rectal disease who had barium enema X-ray examinations. A standard technique was employed. The most consistent measurement was obtained at the level opposite the S3-S4 disc space; readings varied between 2 mm and 16 mm. Using 16 mm as the upper limit of normal, and a similar technique of barium enema examination, the width of the presacral space at the S3-S4 disc level was measured in 66 patients with inflammatory bowel disease (ulcerative colitis--49; Crohn's colitis--17). The width did not correlate with the severity of the disease process as indicated by sigmoidoscopic examination in proximity in time to the radiological examination. There was a relationship between increased width of the presacral space and the duration of the disease process.

Colonoscopy and bacteraemia.

A prospective study was performed on 35 patients undergoing colonoscopy. Aerobic and anaerobic blood cultures before, during and after the investigation failed to demonstrate bacteraemia in any instance.

The effect of tri-potassium di-citrato bismuthate (De-Nol) on the healing of chronic duodenal ulcers.

Forty-six patients suffering from chronic duodenal ulcer, proven endoscopically, were treated in a randomized double-blind cross-over trial with either tri-potassium di-citrato bismuthate (De-Nol) or placebo for four weeks and assessed symptomatically and endoscopically. Those patients who failed to heal after treatment with either agent were crossed over to the alternative preparation and reassessed after a further 28 days. Forty-two patients completed the study involving 57 patient treatments. A highly significant improvement in both symptomatic response (P less than 0.01) and endoscopic healing (P less than 0.01) was seen in those patients receiving tri-potassium di-citrato bismuthate (De-Nol) as against placebo therapy.

Pancreatitis and renal disease.

Pancreatitis has been described previously following renal transplantation, but not in association with chronic renal failure. Analysis of 168 patients with renal transplants revealed five who developed pancreatitis, three of whom died. All five were on treatment with prednisone and azathioprine. Four patients were seen with definite attacks of pancreatitis and chronic, stable renal failure from a variety of causes. None had received immunosuppressive agents, prednisone nor thiazide diuretics, but two were on regular frusemide. One patient was on maintenance dialysis, which could not be related directly to the pancreatitis. In either group alcohol ingestion, cholethiathiasis, or hypercalcaemia was not a factor. This diagnosis of pancreatitis was established on clinical grounds and serum amylast levels of greater than 900 iu/1. Similar serum amylast elevation was not found ina random group of patients with chronic renal failure. Hyperlipidaemia was not present in any patient with pancreatitis. Although hypercalcaemia and primary hyperparathyroidism was not found in the transplant and non-transplant subjects, elevated serum parathormone levels have been described in uraemic patients with normocalcaemia. Hyperparathyroidism may be a factor in the development of pancreatitis in reanl failure. Pancreatitis carries a significant mortality risk in renal transplantation. The four non-transplanted patients have survived, despite recurrent attacks of pancreatitis.

Gastric ulceration within hiatus hernia.

A retrospective analysis has been made of 19 persons with gastric ulceration in hiatus hernias. Eleven patients presented with acute upper gastrointestinal haemorrhage and three with chronic anaemia. Seventeen had experienced previous abdominal discomfort or heartburn. Diagnosis of ulceration was achieved by endoscopy in 16 instances and by radiography in six instances. A chronic ulcer was found in 10 patients, a discrete acute ulcer in three and multiple erosions in six. Twelve of the hernias were sliding in type and irreducible, in contrast to previous reports that gastric ulceration is most frequent in paracoesophageal hernias. Conservative management resulted in complete healing of the ulcer in the majority of patients. Continued bleeding or failure of the ulcer to heal necessitated surgical intervention in six patients.