Intestinal permeability in dermatitis herpetiformis.

Differential absorption of D-xylose and 3-0-methyl-D-glucose, and unmediated intestinal permeation (simple diffusion) of lactulose and L-rhamnose, have been investigated in 20 patients with dermatitis herpetiformis. Both iso-osmolar and hyperosmolar test solutions were employed and the results were compared with those obtained from a group of healthy adult volunteers. The findings in each patient have been correlated with small intestinal histology. The majority of patients with villous atrophy had abnormally raised intestinal lactulose permeation and lactulose/rhamnose permeability ratios, whereas patients with normal small intestinal morphological grading did not differ significantly from the healthy control group in this respect. There was a high incidence of delayed plasma D-xylose absorption peaks in dermatitis herpetiformis irrespective of small intestinal histological findings. These results imply that abnormal intestinal permeability in dermatitis herpetiformis is the result of gluten-induced damage to the mucosa rather than an inherent primary defect. It is therefore improbable that the rash in this condition is purely a manifestation of increased intestinal permeation of antigen.

Balsalazide in the maintenance treatment of patients with ulcerative colitis, a double-blind comparison with sulphasalazine.

Balsalazide (BSZ) is a pro-drug which releases 5-aminosalicylic acid (5ASA) and 4-aminobenzoyl-beta-alanine (an inert carrier) in the colon of various species including man. BSZ was compared with sulphasalazine (SASP) (both 1 g b.d. orally) in the maintenance of remission in patients with ulcerative colitis (UC). Seventy-nine patients (53 male, 26 female), mean age 49 years (range 19-79 years), with UC were randomly allocated to either treatment (41 BSZ, 38 SASP) for 6 months. The groups were similar in respect of age, sex, duration and extent of disease. Seven patients defaulted (3 BSZ, 4 SASP) leaving 38 on BSZ and 34 on SASP. Two male patients, both receiving SASP, were withdrawn because of severe side-effects. One of these patients, with an exfoliative rash, was maintained satisfactorily on open BSZ. Remission rates at 6 months (51% BSZ, 63% SASP) were not significantly different (life-table analysis P less than 0.1). Twelve patients (15%) reported troublesome side-effects (2 BSZ 5%, 10 SASP 26%, P = 0.017 Fisher Exact Test). Mean haemoglobin concentrations, similar on entry, increased after 6 months with BSZ (0.2 g/dl) but decreased with SASP (0.5 g/dl) (P less than 0.0002). BSZ was not significantly different from SASP in maintaining remission in patients with UC but had fewer side-effects.

Improved maintenance of remission in ulcerative colitis by balsalazide 4 g/day compared with 2 g/day.

The efficacy of two doses of balsalazide for the maintenance of remission in patients with ulcerative colitis was compared in a double-blind multicentre trial. Sixty-five patients received a 2 g daily dose, and 68 a 4 g dose. The patient groups were similar at entry for sex, age, and disease distribution. Clinical assessment was carried out at 3-monthly intervals, with sigmoidoscopy, rectal biopsy, and blood tests on entry and at 26 and 52 weeks. Clinical relapse over twelve months was significantly less common on the 4 g dose (36%), than on the 2 g dose (55%), P less than 0.01. There were eight withdrawals on 2 g daily and 13 on 4 g daily, six and nine respectively being mainly due to gastrointestinal intolerance. It is concluded that balsalazide is a well-tolerated drug, and is effective for the maintenance of remission in patients with ulcerative colitis, the optimal dose being greater than 2 g daily.

Colonic variceal bleeding in a patient with mesenteric venous obstruction due to an ileal carcinoid tumour.

Colonic varices are a recognized cause of rectal bleeding in portal hypertension. We report here a patient who presented with melaena several months after resection of an ileal carcinoid tumour. Subsequent colonoscopy for continued episodes of rectal bleeding demonstrated extensive colonic varices. In the absence of portal hypertension, the varices appeared to be related to mesenteric venous obstruction. The management of bleeding colonic varices, in these circumstances, is discussed.

Screening for occult gastrointestinal bleeding in hospital patients.

Stools have been tested for occult gastrointestinal bleeding in 278 outpatients and 170 hospital inpatients using the Haemoccult and Haemastix methods. Seventeen outpatients (6.1%) and 42 inpatients (24%) were positive with the Haemoccult technique. Thirty-three outpatients (11.9%) and 93 inpatients (54.7%) were positive with the Haemastix test. Following investigation of the Haemoccult-positive patients, only 2 cases (3.4%) were considered false positive. However, the false positive rate with Haemastix was 22.9% which is unacceptable in a screening test. Haemoccult may be useful as a screening test for asymptomatic general practice patients, but a test of greater sensitivity is needed for hospital patients.

The clinical value of Haemoccult and Fecatwin in the detection of colorectal neoplasia in hospital and general practice patients.

Four hundred and fifty asymptomatic general practice patients and 330 hospital inpatients had their stools tested for occult blood with the Haemoccult and Fecatwin methods. In general practice, 9/64 (14%) of patients with a positive result had a colonic neoplasm (three carcinomas, one Dukes' Stage A, two Dukes' Stage C, six adenomas) and in hospital 12/142 patients (8%) were found to have colonic tumours, (nine carcinomas, two Dukes' Stage A, two Dukes' Stage B, five Dukes' Stage C and three adenomas). The overall detection rates for colonic neoplasia were 2% in general practice and 3.4% in hospital. In 2 years of follow-up, none of the general practice patients have presented with colonic symptoms. Two hospital patients with colonic carcinomas produced negative tests with both methods. Out of the total of 21 colonic neoplasms, nine were detected by Fecatwin alone, but this trend in favour of the more sensitive test did not reach the 5% level of statistical significance. In contrast, the number of false positive results were significantly greater with Fecatwin than Haemoccult. From our data it would appear that the Fecatwin method warrants assessment in a full controlled trial of its value as a population screening test for colonic cancer.

Moderate drinking during pregnancy and foetal outcome.

Although there are many reports of the adverse effects of alcohol on the infant in ancient literature the first modern report was by Sullivan, Physician to Liverpool gaol. He showed an increased incidence of growth retardation and stillbirth in children of alcoholic mothers using their non-drinking relatives as a control. The literature on moderate drinking is contradictory and suffers from poor control of factors known to confound pregnancy outcome such as social class, parity and smoking habit. The other major problem in assessing the effect of moderate drinking is the difficulty in obtaining accurate drinking histories and the many and varied ways in which these are taken. All histories however, should be regarded as an underestimate. Moderate drinking (less than 40 g alcohol/day before and during pregnancy) has been related to growth retardation, a higher incidence of congenital abnormality, poorer behavioural and neurological scores in the newborn. Recent American surveys have shown an increased relative risk of mid-trimester abortion in women who drink more than three times a week in early pregnancy. Recent work in this country has demonstrated a trend toward smaller head circumference and reduced weight in the babies born to mothers consuming more than 100 g alcohol a week in very early pregnancy. The interaction between smoking and drinking is particularly important for this effect. Using logistic regression analysis the effect of drinking and smoking on birth weight can be clearly seen together with the effect of social class. For any impact to be made on this problem educational intervention is necessary before pregnancy is planned, and thus should be directed at pre-conception clinics, family planning clinics and the general practitioner's surgery.

Oesophageal ulceration due to emepronium bromide.

Four cases of oesophageal damage associated with ingestion of the urinary anti-spasmodic agent emepronium bromide are described. All the patients presented with severe retrosternal pain worsened by swallowing food and drink, and in every case fibre-optic endoscopy revealed ulceration of the midoesophagus. Symptoms disappeared rapidly following cessation of emepromium bromide therapy. The means whereby this agent might injure oseophageal mucosa are discussed.

Heterotopic gastric tissue in the duodenum: a report of eight cases.

Eight patients with intraduodenal gastric heterotopic are described. Seven were under investigation for x-ray-negative dyspepsia, and one presented with repeated attacks of hematemesis. As all of these cases were diagnosed by the use of upper-gastrointestinal endoscopy and biopsy under direct vision, it is likely that more widespread use of these techniques will lead to an increase in the reported incidence of a condition previously thought to be rare.

Platelet prostaglandin production in alcoholic liver disease.

Impaired platelet aggregation is a common finding in patients with alcoholic liver disease. This may be due to impairment of prostaglandin synthesis and alterations in the proportions of platelet membrane lipids secondary to changes in circulating lipids. Platelet prostaglandin synthesis was measured by the production of malonaldehyde (MDA), and was increased in patients with alcoholic cirrhosis compared with normal controls. Mean MDA production in cirrhotics was 3.37 nmoles MDA/10(9) platelets, and in controls 1.01 nmoles MDA/10(9) platelets (p less than 0.01). Platelet prostaglandin synthesis was significantly related to the serum cholesterol:triglyceride ratio (r = 0.73, p less than 0.005). Platelet aggregation was impaired in 12/14 cirrhotics. Five of the cirrhotics had a factor in their plasma which appeared to enhance the aggregation of normal platelets. Impaired platelet aggregation in patients with alcoholic liver disease appears to be due to a defect in intraplatelet metabolism.

Drinkwatchers--description of subjects and evaluation of laboratory markers of heavy drinking.

Clinical examination and measurement of MCV and GGT were carried out on 124 self-referred 'healthy' Drinkwatchers, all of whom had consumed at least 80 g alcohol/day for more than 2 years. The majority (66.1%) were in social classes II and III. Sixty-three subjects (54.1%) had a raised MCV, GGT or hepatomegaly. A raised MCV was significantly more likely to occur in men. Forty-five subjects (36.3%) had an enlarged liver of whom 17 had a normal MCV and GGT. This study shows that MCV and GGT are poor screening tests for excessive alcohol consumption in 'healthy' subjects but, if used at all, MCV appears to be more sensitive in women and GGT in men. Neither test is an adequate substitute for a careful history and full clinical examination.

Cholangiocarcinoma and oral contraceptives.

PIP: A 21-year-old woman presented with a 12-month history of epigastric pain, and for 3 months she had noticed a mass in the right hypochondrium. She had taken 'Norinyl-1' (norethisterone 1 mg and mestranol 50 mcg) for 5 years. She smoked 20 cigarettes a day but drank little alcohol. Physical examination revealed irregular hard hepatomegaly 10 cm below the right costal margin. Hepatitis B surface antigen was not detected in the serum and alpha fetoprotein levels were normal ( 10 M.R.C. units). A liver scan showed a large space-occupying lesion in the right lobe of the liver, and liver biopsy revealed a cholangicarcinoma with striking fibrous reaction. Multiple shadows consistent with metastases were present on chest X-ray, but no bony deposits were found on radiological skeletal survey or bone scan. The serum calcium was persistently high (2.74-2.92 mmol/l) but fell on prednisolone therapy. Serum parathyroid hormone levels were normal. A causal relation between oral contraceptives and hepatic adenoma is now generally accepted, and several patients with hepatocellular carcinoma have also been reported. We have been able to find only 1 previous report of cholangiocarcinoma in a young female taking oral contraceptives, and there is 1 report of this tumor in a man taking high doses of anabolic steroids for refractory anemia. This tumor has its peak incidence in the 6th decade and is very rare in the 3rd decade. The association with hypercalcemia due to pseudohyperparathyroidism is well recognized. In only some cases are parathyroid hormone levels raised, and the cause of the pseudohypercalcemia in our patient is unknown.^ieng

Bloody diarrhoea: a rare presentation of a systemic disease.

Bloody diarrhoea in adolescents is usually due to enteric infection or inflammatory bowel disease. We describe a patient with bloody diarrhoea and endoscopic features of colitis in association with a systemic vasculitis. Positive anti-proteinase-3 antineutrophil cytoplasmic antibodies and cutaneous vasculitis on biopsy confirmed the diagnosis of Wegener's granulomatosis. He was started on high dose steroids and cyclophosphamide but required plasmapheresis for a declining renal function. The case highlights the need for vigilance with common clinical problems, because a life-threatening condition may be averted by prompt recognition and urgent therapy with immunosuppressants.

Ileal endometriosis masquerading as Crohn's ileitis.

Endometriosis is usually confined to the pelvis but may involve distant organs. When the small bowel is affected, endometriosis has a propensity to develop in the distal ileum, which may lead to fibrosis and stricture formation that can be confused with Crohn's disease. Here were describe two women, one with antecedent Crohn's colitis in whom ileal endometriosis mimicked obstructing Crohn's disease of the terminal ileum. These reports illustrate that ileal endometriosis must be considered in the differential diagnosis of Crohn's disease of the ileum, even in the presence of Crohn's disease elsewhere in the gastrointestinal tract.

Cell-mediated immunity in HBeAg-positive homosexuals with chronic liver disease.

Chronic liver disease developing after infection with the hepatitis B virus may be due to impairment of cell-mediated immunity (CMI). In a study of CMI by the lymphocyte transformation test to two mitogens and hepatitis B surface antigen (HBsAg) the response to the mitogens, phytohemagglutinin (PHA) and purified protein derivative (PPD), was normal in all of 15 male homosexuals with HBsAg-positive chronic liver disease, indicating a normal non-specific cellular immune response. By contrast, only one of the 15 patients showed a response to HBsAg, which may explain the high prevalence of chronic HBsAg carriage in these patients.

Upper gastrointestinal Kaposi's sarcoma in patients positive for HIV antibody without cutaneous disease.

Six patients with antibodies to the human immunodeficiency virus (HIV) and with persistent gastrointestinal symptoms of HIV infection but without cutaneous lesions of Kaposi's sarcoma underwent endoscopy. Four also underwent barium meal examination. In all six cases small lesions were seen in the stomach at endoscopy, and histological examination of biopsy specimens taken from the lesions confirmed the diagnosis of Kaposi's sarcoma. The barium meal examinations were reported as normal in three patients and showed oesophageal candidiasis in the fourth. These findings suggest that Kaposi's sarcoma of the upper gastrointestinal tract is common in patients positive for HIV antibody, even those without cutaneous lesions. Endoscopy, with biopsy of suspicious lesions, is necessary to make the diagnosis and is recommended in all HIV antibody positive patients with persistent upper gastrointestinal symptoms.

Idiopathic retroperitoneal fibrosis--is serum alkaline phosphatase a marker of disease activity?

Two patients are presented in whom extensive investigations were carried out to determine the cause of a raised serum alkaline phosphatase. Idiopathic retroperitoneal fibrosis was diagnosed in both cases and the serum alkaline phosphatase returned to normal following treatment with corticosteroids and coincident with resolution of the patients' symptoms.

Effects of moderate alcohol consumption and smoking on fetal outcome.

Previous studies of the effects of moderate drinking on the outcome of pregnancy are assessed. The results of a prospective study of the association between alcohol consumption in pregnancy and birthweight, length of baby, head circumference and premature delivery are described. Consumption of more than 10 g alcohol per day in very early pregnancy or even before conception approximately doubled the risk that the infant would have a low birthweight. Cigarette smoking was also a risk factor for low birthweight. It may therefore be beneficial for women to reduce their alcohol consumption to one drink a day or less from before conception and give up smoking as well.