Primary biliary cirrhosis and chronic active hepatitis: an examination of clinical, biochemical, and histopathological features in differential diagnosis.

Seventy four liver biopsies from 59 patients were reviewed by two observers and histologically graded in the absence of clinical information, firstly, to assess the level of agreement with previous diagnoses; secondly, to identify differences between primary biliary cirrhosis and chronic active hepatitis; and, thirdly, to assess the specificity of Shikata orcein staining and antimitochondrial antibody positivity and titre for primary biliary cirrhosis. Thirty six patients with adequate histology were initially selected as typical of primary biliary cirrhosis or chronic active hepatitis; agreement both between observers and with original diagnoses was reached in 26 (72%) (15 with primary biliary cirrhosis (group 1), 11 with chronic active hepatitis (group 2)). In 19 diagnostically difficult patients in whom clinical and original histological findings had been at variance, histological agreement between observers was reached in 17 (group 3) and original underdiagnosis of primary biliary cirrhosis was suggested. The main clinical and histological differences between groups 1 and 2 are discussed in this paper. Although a high grade of positivity for copper associated protein in the Shikata orcein stain was seen only in primary biliary cirrhosis, a high titre of antimitochondrial antibody positivity was not unique to this condition.

Case of a late presentation of cor triatriatum in a woman born with an imperforate anus.

Cor triatriatum and imperforate anus are rare. We describe, for the first time, the coexistence of these conditions in a 43 year old woman.

Guillain-Barré neuropathy during treatment with captopril.

A patient is described who developed acute peripheral neuropathy of Guillain-Barré type occurring shortly after commencement of captopril for moderately severe hypertension and resolving after discontinuation of the drug.

Pseudostone at ERCP due to juxtapapillary diverticulum.

Juxtapapillary diverticula of the duodenum are often encountered at endoscopic retrograde cholangio pancreatography (ERCP) and their presence causes a prominent "pseudostone" appearance on the retrograde cholangiogram in many patients with otherwise normal, i.e. stone-free, ducts. This may lead to inappropriate surgery if not recognised.

Coeliac disease and autoimmune thyroid disease.

A well defined cohort of coeliac patients was studied prospectively to assess the prevalence of coexisting thyroid disease and positive thyroid autoantibodies. Comparison with epidemiological data on the prevalence of coeliac disease in a neighbouring area suggested that few adult coeliac patients had been missed. Overall, 14% of the coeliac patients had thyroid disease: 10.3% were hypothyroid and 3.7% hyperthyroid, both significantly more than expected. There were significantly more coeliac disease patients with thyroid autoantibodies than expected--11% had thyroglobulin antibodies and 15% had thyroid microsomal antibodies. This association is clinically important. Three patients are described in whom the coexistence of coeliac disease and hypothyroidism led to diagnostic difficulties and delay of treatment.

Nitrite and thiocyanate in the fasting and secreting stomach and in saliva.

The concentrations of nitrite and thiocyanate in fasting and pentagastrin stimulated gastric juice and in saliva have been examined. Nitrite was found in all of 17 samples of fasting gastric juice, mean 4-9 +/- 1-1 muM. Stimulation of gastric secretion with pentagastrin caused no significant change in nitrite concentration. Thiocyanate was detected in all of 21 samples of fasting gastric juice and the difference in concentration between smokers and non-smokers probably reflects similar differences in saliva. In contrast to the nitrite data there was a significant drop in thiocyanate concentration of gastric juice after pentagastrin from 0-9 +/- 0-1 mM to 0-3 +/- 0-04 mM, suggesting a salivary origin for the thiocyanate in gastric juice. Thiocyanate is a powerful catalyst of nitrosation, which, together with small amounts of nitrite and naturally occurring amines could lead to the intragastric formation of carcinogenic nitrosamines and in certain circumstances be a factor in the aetiology of gastric cancer.

Rectal potential difference and histology in Crohn's disease.

The rectal potential difference (PD) was measured in 27 patients with Crohn's disease, and in 16 subjects without gastrointestinal disease to establish a normal range. Sigmoidoscopic assessment and rectal biopsy were performed in all patients with Crohn's disease, and the mean resting rectal PD was significantly reduced in patients with sigmoidoscopically active disease and in those with abnormalities of the superficial epithelium on rectal biopsy. Patients with diarrhoea had a significantly lower mean resting PD than those with normal bowel habit, suggesting that an abnormality of rectal sodium transport may be contributing to the diarrhoea in these patients. The response of rectal PD to mineralocorticoid stimulation with oral fludrocortisone was measured in 13 patients. The PD failed to rise only with patients with sigmoidoscopically active disease, and the test proved to be a less sensitive indication of minor mucosal abnormalities than sigmoidoscopy of biopsy.

The diagnostic yield of ERCP in the investigation of unexplained abdominal pain.

One hundred and forty patients with undiagnosed severe chronic abdominal pain who had not undergone previous biliary surgery were investigated by ERCP. A diagnosis was achieved in 34 patients (24 per cent) including 8 with previously undiagnosed peptic ulceration and 5 with gallstones. Twenty-five patients (18 per cent) had an abnormal pancreatogram, including 1 with pancreatic cancer. The incidence of pancreatogram abnormalities suggestive or diagnostic of pancreatitis was particularly high (60 per cent) in patients with a history of alcohol abuse. ERCP has a valuable role in the investigation of patients with 'obscure' abdominal pain.

Clinical value of serum immunoreactive trypsin concentration.

The clinical value of estimation of serum concentrations of immunoreactive trypsin was evaluated by studying 46 healthy controls, 23 controls in hospital, 44 patients with chronic pancreatic disease, and 184 patients with non-pancreatic conditions in which pancreatic disease commonly enters into the differential diagnosis. Serum trypsin concentration had a log normal distribution in the controls, and the calculated normal range was considerably wider than that previously reported. The concentration was abnormal in only 13 out of 27 patients with chronic pancreatitis and was extremely variable in patients with pancreatic cancer. Abnormal results occurred in 11% of the patients with non-pancreatic disease. Eighteen patients had a subnormal trypsin concentration, of whom six did not have pancreatic disease and 12 had either chronic pancreatitis or pancreatic cancer. There was no correlation between serum trypsin concentration and mean tryptic activity as measured by the Lundh test. Of 11 patients with pancreatic steatorrhoea, only seven had subnormal trypsin concentrations. There results suggest that the serum concentrations of immunoreactive trypsin has a low specificity and sensitivity for pancreatic disease and does no reflect the degree exocrine insufficiency in patients with proved chronic pancreatitis.

Endoscopic retrograde cholangiography and pancreatography in investigation of post-cholecystectomy patients.

102 severly symptomatic post-cholecystectomy patients were studied by endoscopic retrograde cholangiography (ERCP), and successful ampullary cannulation was achieved in 101. All 29 patients with jaundice were correctly classified into intrahepatic and extrahepatic causes. 8% (73) patients with abdominal pain but no history of jaundice had retained biliary calculi, and 25% had an abnormal pancreatogram suggesting pancreatitis. The measurement of bileduct calibre alone did not reliably distinguish between the presence or absence of retained stones. It is suggested that ERCP is the investigation of choice in the symptomatic post-cholecystectomy patient.

Treatment of distal ulcerative colitis (proctosigmoiditis) in relapse: comparison of hydrocortisone enemas and rectal hydrocortisone foam.

Thirty patients with distal colitis (proctosigmoiditis) in relapse were randonly allocated to twice daily treatment with traditional aqueous hydrocotrisone enemas (Cortenemas) or a suspension of hydrocortisone in an inert foam base (Colifoam). Each treatment contained the same amount of hydrocortisone. Clinical, sigmoidoscopic, and histological response was assessed after two weeks. Both agents were effective, and broadly similar in terms of objective improvement, but subjective improvement was greater with the foam preparation, and several patients expressed a preference to this mode of treatment.

The endoscopic retrograde cholangiogram and pancreatogram in chronic liver disease.

The endoscopic retrograde cholangiogram and pancreatogram of 22 patients with primary biliary cirrhosis, 33 patients with other forms of chronic liver disease and 28 'normal' controls were compared. The incidence of radiological intrahepatic duct abnormality is similar in patients with primary biliary cirrhosis and in other forms of liver disease, but is present in only a minority of both groups. A 'notch' or smooth indentation on the extrahepatic bile ducts at the porta hepatis was present in 58% of patients with primary biliary cirrhosis but in none in either of the other two groups. Three out of seven patients with sclerosing cholangitis showed minimal-change pancreatitis. Pancreatic abnormalities were otherwise infrequent.

Pathogenesis of gastric cancer in pernicious anaemia.

A pathogenetic mechanism to explain the increased incidence of gastric cancer in patients with pernicious anaemia (P.A.) is proposed. Mean nitrite concentration in gastric juice from thirteen fasting patients with P.A. was nearly fiftyfold greater than that of age-matched controls. The number of bacteria in the gastric juice of P.A. patients was also greatly increased. Small amounts of volatile nitrosamines were detected in simulated P.A. gastric juice in vitro, after addition of nitrite to achieve a concentration approximating to that found in vivo. If similar nitrosation occurs in vivo, the intragastric production of carcinogenic N-nitroso compounds could explain the high incidence of gastric cancer in patients with P.A.

Endoscopic retrograde cholangiograms of the normal and post-cholecystectomy biliary tree.

The diameter of extrahepatic and intrahepatic bile ducts was measured on 50 normal retrograde cholangiograms and on the cholangiograms of 109 post-cholecystectomy patients undergoing endoscopic retrograde cholangiopancreatography: 70 of the post-cholecystectomy patients had a normal cholangiogram and 39 had retained stone or biliary stricture, of whom 17 were jaundiced. Biliary diameter at all points measured was greater in the post-cholecystectomy patients with no biliary lesion than in normals, and further increased in the presence of pathology (e.g. retained stone). The extent of overlap in biliary diameter between all these three groups is so great that measurement of bile duct calibre cannot separate patients with retained stone from post-cholecystectomy patients without retained stone, or from patients with an entirely normal biliary tree, even in the presence of obstructive jaundice. Methods of evaluating the biliary tract which rely on the measurement of bile duct diameter (e.g. ultrasound) are therefore of limited value in the investigation of post-cholecystectomy patients.

Clinical relevance of an unfused pancreatic duct system.

In man, the main pancreatic duct is normally derived from ventral and dorsal embryological buds of the pancreas. In a minority of people, failure of fusion of the two buds results in separate drainage of the dorsal and ventral pancreas, so that the accessory duct provides the main drainage for the gland. Patients with this anomaly demonstrated at endoscopic retrograde pancreatography (ERP) have been investigated to assess whether non-fusion of the main pancreatic duct predisposes to the development of pancreatitis. A failure of fusion of the pancreatic ducts was seen in 21 out of 449 (4.7%) successful pancreatograms; four of these 21 patients had definite clinical evidence of pancreatitis and two patients had possible pancreatic disease, but in the remainder the anomaly was not considered to be clinically relevant. An abnormal pancreatogram suggesting pancreatitis was present in 116 out of the 428 patients (27.1%) with a normally fused duct system. The anomaly was found as frequently in the whole series as it was seen in patients with pancreatitis. These findings suggest that embryological failure of pancreatic duct fusion does not predispose to the development of pancreatitis. However, the presence of this anomaly may lead to misinterpretation of ultrasonographic and CT scan findings.

Gastric bacteria, nitrate, nitrite and nitrosamines in patients with pernicious anaemia and in patients treated with cimetidine.

Patients with pernicious anaemia have a high risk of gastric cancer and we are investigating the role of N-nitroso compounds in their gastric carcinogenesis. We have carried out bacteriological studies and analyses of nitrite and N-nitroso compounds. Patients with duodenal or gastric ulcer are often treated with H2-receptor inhibitors such as cimetidine. This treatment induces hypochlorhydria similar to that in pernicious anaemia patients and it has been suggested that this might put these patients at risk of developing gastric cancer later. Analyses similar to those for p.a. patients have therefore been carried out in patients treated with cimetidine. We have set up an animal model of achlorhydria, using piglets, that will allow us to test in vivo the efficacy of compounds known to inhibit N-nitrosation in vitro. This is clearly necessary, in view of the growing size of the population now thought to be at risk.

Effect of cimetidine on the gastric bacterial flora.

Bacteriological studies were carried out on samples of gastric juice obtained from 31 patients with peptic ulcer before and immediately after a month's course of cimetidine. After cimetidine there were major increases in both total bacterial counts and counts of nitrate-reducing organisms and qualitative changes suggesting the establishment of a flora which included large numbers of "faecal" organisms.

Gastric-juice nitrite. A risk factor for cancer in the hypochlorhydric stomach?

Nitrite and hydrogen ion concentrations have been measured in the fasting gastric juice of 69 patients undergoing routine gastrointestinal investigations. There was an inverse relationship between nitrite concentration and hydrogen ion concentration, with a highly significant increase in gastric-juice nitrite in hypochlorhydric subjects. Thiocyanate was also found in all specimens in concentrations likely to increase nitrosamine formation, if nitrosation of amines occurs in the fasting stomach. Neutral gastric juice contains metabolically active bacteria capable both of generating nitrite from nitrate and of catalysing nitrosation. In this way an intragastric environment suitable for the formation of carcinogenic nitrosamines exists in the hypochlorhydric and achlorhydric stomach, providing a possible mechanism for the high incidence of gastric cancer in these subjects.

A comparison of prednisolone enemas with low-dose oral prednisolone in the treatment of acute distal ulcerative colitis.

The therapeutic efficacy of prednisolone metasulphobenzoate enemas in the treatment of distal colitis has been compared with that of low-dose oral prednisolone, in a single-blind, cross-over trial. Treatment with steroid enemas resulted in symptomatic and sigmoidoscopic evidence of improvement more frequently than treatment with a dosage of oral steroid calculated to achieve similar plasma prednisolone levels. In addition to demonstrating, for the first time, that prednisolone metasulphobenzoate enemas are effective in the treatment of colitis, this study suggests that their efficacy is due to a local action rather than systemic absorption.