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The effects of bedtime 70 micrograms and twice daily 35 micrograms doses of enprostil on 24-hour intragastric acidity were investigated in nine duodenal ulcer patients in remission. Median nocturnal acidity decreased significantly by 30% with 35 micrograms twice daily, and by 48% with 70 micrograms at bedtime. In a clinical trial using bedtime dosing, 102 duodenal ulcer patients randomly received either ranitidine 300 mg or enprostil 70 micrograms. More ulcers healed after 4 and 8 weeks treatment with ranitidine than with enprostil (76% ranitidine vs 52% enprostil, at 4 weeks p = 0.0065 and 94% vs 68%, respectively at 8 weeks, P = 0.0007). However, 6 months after cessation of treatment there was no material difference in overall outcome. Despite combining mucosal protection with acid inhibition enprostil treatment conferred no advantage over simple acid inhibition.

Azathioprine toxicity complicated the management of four patients with inflammatory bowel disease. All patients received the drug as adjunctive therapy to steroids when responses to the latter were poor. After a variable sensitising period the patients developed severe diarrhoea and abdominal pain and this was believed at first to be a manifestation of their underlying diseases but rechallenge with azathioprine reproduced the problem. During three episodes described emergency admission to hospital and resuscitation with intravenous fluids was required. The cases illustrate the difficulty clinicians have in recognising drug induced effects which mimic the underlying disease. When a patient suspects a reaction to azathioprine we believe any rechallenge should only be undertaken in the controlled hospital environment.

Pneumatosis cystoides intestinalis (PCI) is an uncommon condition of unknown aetiology. Bacterial gas production may be an important aetiological factor, but experimental evidence in humans has been lacking. We have studied breath hydrogen excretion as an index of bacterial gas production in 12 patients with PCI and have shown that four out of five with demonstrable cysts produced unusually high levels of hydrogen while fasting. This abnormality has not been previously reported. One patient showed resolution of PCI after antibiotic treatment. These findings confirm the importance of bacterial gas production in the pathogenesis of PCI.

Analysis of statistics published since the Abortion Act showed that from 1972 about half the abortions carried out on residents of England and Wales had been performed within the National Health Service. Regional variations in the proportions of abortions performed within the NHS had persisted. In some health regions fewer abortions were being carried out than before. In 1975 about 40% of abortions on single women and women with no existing children were performed within the NHS. Trends in the concurrent sterilisation rate, gestational age at operation, duration of stay in hospital, and mortality and complication rates suggested a steady improvement in the effectiveness and efficiency of abortion services. Nevertheless, the NHS still compares poorly with the private sector and some other countries.

In a case-control study 280 patients with inflammatory bowel disease and matched community controls taken from general practitioner lists were questioned about their smoking habits. Whether assessed by current or previous habits, patients with Crohn's disease were more likely to be or have been smokers than their matched controls and the association appeared strongest at disease onset (matched relative risk 4.1, p less than 0.001). In contrast, patients with ulcerative colitis assessed in the same way were less likely to be smokers compared with their matched controls, with the association being equally strong at disease onset and currently (matched relative risk 0.17, p less than 0.001). Among patients with ulcerative colitis who were exsmokers, 76% reported stopping smoking before disease onset compared with 13% of exsmokers with Crohn's disease. Contrary to earlier reports, there were only small and nonsignificant increases in the risk of Crohn's disease or ulcerative colitis in exsmokers. The strength, temporal precedence, and contrasting nature of the associations are evidence that smoking has an important etiologic role in inflammatory bowel disease. Smoking appears to be a factor in determining whether Crohn's disease or ulcerative colitis develops in predisposed individuals.

A protein-bound Schilling test incorporating chick serum was used to study 16 elderly vitamin B12-deficient inpatients. Thirteen of these also underwent standard Schilling tests. They were compared with an age-matched control group of non-deficient inpatients. The lower limit of normal for assimilation of protein-bound vitamin B12 was 0.7%. Fourteen out of 16 deficient patients assimilated protein-bound vitamin B12 subnormally. Twelve of these were fully Schilling tested. Five assimilated free B12 normally, and five responded to intrinsic factor. One patient did not respond to intrinsic factor and had jejunal diverticulosis and one could not be categorized. One of two patients with normal assimilation had a borderline vitamin B12 intake. No subjects had neurological sequelae and only three were anaemic. In this population, B12 deficiency is usually asymptomatic but nearly always results from impaired assimilation possibly justifying replacement therapy. Schilling testing only affects treatment if there is other evidence of small-bowel dysfunction.

The association of primary biliary cirrhosis and coeliac disease, not previously reported, was observed in 4 patients. In each case, the two conditions were diagnosed simultaneously, and although symptoms were due to coeliac disease, initial investigation drew attention to the liver condition. All the patients responded to a gluten-free diet and remain well 2 years later. Primary biliary cirrhosis remains asymptomatic in 3 patients, but pruritus has developed in the 4th. The significance of this association is unclear and may merit formal study. Coeliac disease should be considered as a possible cause of unexplained weight loss in primary biliary cirrhosis.

From 1960 to 1979 there was a threefold increase in the number of cases of coeliac disease diagnosed annually in adults in Edinburgh and the Lothians. Women accounted for 80% of the increase and their mean age at diagnosis was significantly reduced. The ratio of female to male new cases changed from 1.25 in the '60s to 2.5 in the '70s. In the period 1975-9 56 of 102 adults with coeliac disease presented with no gastrointestinal symptoms, including 30 cases diagnosed as a result of minor biochemical or haematological abnormalities, such as red-cell macrocytosis without anaemia. Over the same period, only 13 presented with a typical malabsorption syndrome compared to 24 of 38 (63%) in the years 1960-4. During 1975-9 58 new cases had no anaemia, compared with eight (21%) in the earlier period. Hypoproteinaemia (concentration less than 60 g/l) and hypocalcaemia of less than 2.00 mmol/l (8 mg/100 ml) were also less common. Though a real increase in the incidence of coeliac disease cannot be discounted, these changes are more likely to be the result of greater awareness of the disease and a lowered threshold for investigation.

A 49-year-old woman with morbid obesity was found to have subtotal villous atrophy in an operative jejunal biopsy, taken when a jejunoileal bypass was created. After the operation, the patient developed marked weight loss, vomiting, hepatic failure, and a bizarre mental state with sudden losses of consciousness. Six months after the first operation the bypass was reversed but the patient developed hepatorenal failure and died one week after the second operation. The histological features of several biopsies of jejunum were typical of a gluten sensitive enteropathy. This, previously subclinical, small bowel disease may have contributed to her hepatic failure and death by interfering with jejunoileal adaptation. In the absence of any of the other, rarer, causes of villous atrophy, this woman appears to have had coeliac disease.

In a case-control study of smoking and ulcerative colitis patients with the disease were much less likely to smoke than community controls matched for age and sex. The difference was substantial, with an estimated relative risk of 3.8 for non-smoking on current habits, was even larger (6.2) when habits at onset of the disease were examined, and was mainly accounted for by 42 of 55 patients who had given up smoking a mean of eight years before onset. The association could not be explained by confounding by social class. These findings suggest that smoking directly or indirectly confers protection against ulcerative colitis.

In a retrospective analysis of 64 deaths from acute upper gastrointestinal bleeding in Edinburgh Royal Infirmary, 46 of the patients (72%) were found to have been over 60 years of age. Recurrent or continuous bledding occurred in 24 cases; after exclusion of deaths from sudden exsanguination (9) and from bleeding varices with subsequent hepatic failure (11), only 4 patients died from recurrent bleeding. Other causes of death were postoperative complications (20) and other severe concomitant disease (20). These results suggest that improved diagnostic techniques such as endoscopy may not significantly reduce the mortality from acute upper gastrointestinal bleeding.

In a case-control study 142 patients with Crohn's disease, 189 patients with ulcerative colitis and matched community controls were questioned about their smoking habits. When assessed by smoking habits before the onset of disease, patients with Crohn's disease were four times as likely to have been smokers than their matched controls. In contrast, patients with ulcerative colitis were ten times less likely to have been smokers compared with their matched controls. There was no confounding by social class or alcohol intake differences. The contrasting nature of these associations suggests that there might be an aetiological role for smoking in inflammatory bowel disease.

We have examined the effects of parasite infection on the mucosal architecture of mice maintained on an elemental diet (Vivonex). Techniques used were conventional histology, micro-dissection and measurement of individual villi and crypts, and measurement of crypt cell proliferation rate by a metaphase accumulation technique. In normal, non-parasitised mice the elemental diet caused no change in villus height, crypt depth, or crypt cell proliferation. Likewise, the only effects of chronic protozoal infection or Nippostrongylus brasiliensis infection on the intestine of mice fed a normal diet have been a slight crypt hypertrophy and an increase in crypt cell proliferation rate without villous atrophy. However, the combination of elemental diet and parasite infection resulted in increased mucosal damage when compared with infected mice on a normal diet. Elemental diet mice infected with the nematode Nippostrongylus brasiliensis had significantly reduced villus height and correspondingly raised crypt length and metaphase accumulation rate. Elemental diet mice infected with the protozoan Giardia muris did not have villous atrophy but there was a significant increase in crypt length and metaphase accumulation when compared with infected normal diet mice. These experiments show that in two animal models of enteric infection, elemental diet has altered the host parasite relationship to the detriment of the host.

To investigate the role of drugs in the rising incidence of fractures of the femoral neck in the elderly a case-control study inquiring about the use of prescribed drugs was carried out. The drug histories of 102 patients with femoral neck fractures were obtained from general practice records and compared with those of 204 controls matched for age and sex from the same practices. At the time of fracture 41 patients with fractures and 126 controls were receiving at least one prescription (relative risk of fracture of the femoral neck in patients taking drugs = 0.42, p = 0.0006). For all types of prescribed drugs except antibiotics the risk of fracture of the femoral neck was less in patients taking drugs than in those not doing so, and this was true at all times in the year before fracture. Six patients with fractures were receiving thiazide diuretics compared with 37 controls (relative risk 0.28, p = 0.004). These results indicate that, contrary to popular belief, drugs that sedate or that impair postural control are not important factors in fractures of the femoral neck. The results are consistent with the hypothesis that the hypocalciuria induced by thiazides protects against fracture, but the degree of protection is not significantly greater than that associated with other drugs.

Paired studies of gastric emptying were performed in 10 healthy volunteers using a scintiscanning technique which provides information about the rate of emptying of both the liquid and solid components of a standard meal. Emptying rates of both components were not significantly different after oral administration of 400 mg cimetidine than after placebo. The increase in serum gastrin concentration produced by the meal was significantly greater after cimetidine than after placebo but there was no relationship between individual cimetidine-placebo differences in gastrin response and the corresponding cimetidine-placebo differences in rates of emptying. A positive correlation was demonstrated between the gastric emptying rate of the liquid component and the 1 h cimetidine absorption, indicating that normal individual variation in gastric emptying is probably responsible for much of the normal individual variation in the rate of cimetidine absorption.

The outcome in 1017 patients with haematemesis and malaena referred to two major hospitals in Nottingham within a 2-year period has been prospectively evaluated. Ninety one (9%) patients died during the time period under consideration and all but four were found to have been over 60 years of age. There were 13 (14%) deaths following rebleeding, of whom 5 (5%) could have been potentially avoided by alterations in management. Some improvement of mortality might result from intensive-care facilities with better management of transfusions and earlier detection of rebleeding allowing earlier endoscopy or surgery. The majority of patients (81%), however, died from concomitant disease which was exacerbated by gastrointestinal haemorrhage or bleeding developed in patients with an already existing end-stage disease. These results show that a reduction of mortality in patients with gastrointestinal bleeding is hampered by the high number of poor-risk patients. The rise in the proportion of elderly patients with this disorder seems to continue.

An association between sarcoidosis and coeliac disease is suggested by the occurrence of both diseases in 5 patients. In 3 cases the gastrointestinal symptoms of coeliac disease preceded those of sarcoidosis and in the other 2 patients symptoms of both diseases appeared at the same time.

Medical students in Nottingham all complete an honours Bachelor of Medical Sciences course in one department including a research project. The honours programme in community health is described, with results from a survey of the 122 graduates since the medical school started. The 98 (80%) responses showed high levels of satisfaction and gain from the programme, the great majority regarding the course as valuable, enjoyable, and giving both research skills and skills in interpersonal relationships.