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We studied 154 patients presenting with significant colonic symptoms and subsequently diagnosed to have colorectal carcinoma. They were investigated by faecal occult blood tests, fibresigmoidoscopy, double contrast barium enema (DCBE) and colonoscopy. Faecal occult blood tests (Haemoccult) alone were positive in 26% of patients with Dukes' A, in 69% with Dukes' B and in 64% with Dukes' C lesions. DCBE alone identified the lesion in 32% of Dukes' A, 79% of Dukes' B and 81% of Dukes' C carcinomas. Fibresignoidoscopy diagnosed colorectal malignancy in 84% of patients with Dukes' A, 90% with Dukes' B and 81% with Dukes' C stage. A diagnostic yield of 88% for Dukes' A, 96% for Dukes' B and 100% for Dukes' C carcinomas was seen with colonoscopy. Detection rate for all stages of carcinoma was greater than 95% when fibresigmoidoscopy and DCBE were used together. Faecal occult blood tests and DCBE alone are inadequate in diagnosing early malignancy in symptomatic patients. Fibresigmoidoscopy and DCBE used in conjunction compare favourably with the technically difficult procedure of colonoscopy and should routinely be undertaken in these patients before malignancy can confidently be excluded.

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The Project described in this paper was the development of a micro-computerised database of the management of patients presenting to a hospital clinic with abdominal pain. The database contains clinical, resource use and cost information, and was used to aid the consultant in charge to assess and monitor his patterns of management. During the course of this project, and arguably partly because of the information provided, the overall cost per patient fell by 25%. The project was carried out by the Health Services Research Unit at the University of Warwick between 1982 and 1986, the principal investigator being J.A. Stilwell. The collaborating Health Authority was Dudley, and the Consultant Gastroenterologist was Dr A.N. Hamlyn. Finance was provided by the Department of Health and Social Security.

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A total of 541 open access referrals for fibresigmoidoscopy over five years were compared with 495 hospital initiated procedures during the same period. The number of open access fibresigmoidoscopies doubled during the five years but diagnostic yield remained unchanged at about 40% and was similar to that of the hospital initiated procedures. Colorectal carcinoma was seen in 64 open access patients compared with 47 hospital referred patients, the proportion of Dukes's type A lesions being similar (34%) in both groups. Polyps, colitis, and diverticular disease were equally common in open access and hospital referred patients. Fibresigmoidoscopy failed to detect disease in only 12 patients (1.2%) and the procedure was unsatisfactory in only 54. Referral was considered justified in 475 (88%) open access patients, and only 54 (17%) patients with normal appearances at endoscopy required further investigations. Diagnostic yields were low (19%; 30/156 cases) in open access patients under 40 and in patients with abdominal pain, constipation, or abdominal pain with constipation (0-17%). Most of these young patients presumably suffer from the irritable bowel syndrome and do not justify fibresigmoidoscopy. In contrast, there was a high diagnostic yield (90-100%) in patients of all ages referred for diarrhoea and rectal bleeding, altered blood from the rectum, and rectal bleeding associated with abdominal pain. Open access fibresigmoidoscopy is an effective service that should be freely available to general practitioners.

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169 hospital inpatients were studied to assess the association of blue sclerae with iron-deficiency anaemia. Three observers independently graded the signs of blue sclerae and mucosal pallor as absent, equivocal, definite, or striking. Blue sclerae were seen more often in patients with iron-deficiency anaemia (40/46, 87%) than in those with other anaemias (2/28, 7%; p less than 0.001) or without anaemia (5/95, 5.3%; p less than 0.001). The specificity of blue sclerae in iron-deficiency anaemia was 0.94 with a sensitivity of 0.87. By comparison, mucosal pallor was noted in only 30% of patients with iron-deficiency anaemia, with a specificity of 0.96 and a sensitivity of only 0.20 (p less than 0.001). The presence of blue sclerae was unaffected by age, sex, or colour of iris. Blue sclerae appear to be a good indicator of iron deficiency and should become a regular part of clinical examination.

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Patients with primary biliary cirrhosis (primary non-suppurative destructive cholangitis) in the north east region of England were studied over a five year period and, to evaluate epidemicity, compared with two contemporaneous disease series of known occurrence. These were: terminal renal failure, all causes (low or absent epidemicity n = 106) and an outbreak of echovirus 19 disease (high epidemicity n = 201). Eight primary biliary cirrhosis-affected men and 109 women from an estimated catchment population of 2.08 million were identified. The current diagnosis rate was 1.0/100 000 (1.8/100 000 for women of 15 or more). There were 18 deaths, mean survival from diagnosis 4.0 years. Within the region prevalence varied from 3.7/100 000 in rural areas to 14.4/100 000 in industrial urban areas. In the conurbation, prevalence rates varied insignificantly. Here, most cases were concentrated in central districts, where the proportion of asymptomatic presentations was 50%. Outside the conurbation the asymptomatic proportion fell to 21%, suggesting low incidental diagnosis rates. When compared with echovirus 19, primary biliary cirrhosis was of low or absent epidemicity, and similar to renal failure in its uniform geographical distribution and lack of clustering. Forty three patients (37% of the total), however, had significantly seasonal symptomatic presentations (p less than 0.01), although scan statistic testing failed to show clustering of onset in time. Apparently provocative factors associated with primary biliary cirrhosis symptomatic onset were identified in only 11 (9.4%) of patients. Age-specific onset rates rose linearly between ages 35 and 65, and nearly one third of patients presented after 65 years, two thirds of deaths occurring in this age group. There is thus no evidence in north east England of geographical anomalies in the distribution of primary biliary cirrhosis. International differences may be partly explained by environmental factors influencing seasonal presentation, such as sunlight. Diagnosis rates are profoundly influenced by increased medical awareness, especially in the elderly, of this now relatively common disease and increased use of the mitochondrial (AMA) antibody test.

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Liver tissue samples from 111 patients with various hepatic disorders including 37 with primary biliary cirrhosis (PBC) and 22 with chronic active hepatitis (CAH) were studied. Of the PBC patients, 33 out of 37 (89%) showed orcein-positive and rubeanic acid-positive intrahepatocytic copper granules. In the 4 negative cases conventional staining methods revealed characteristic bile duct lesions and granuloma formations; all 4 were so-called presymptomatic patients. Amongst the liver biopsy samples from CAH patients, 12 out of 22 (55%) contained orcein-positive granules, but none showed stainable copper. We conclude that (1) combined orcein and rubeanic acid positivity in liver samples helps to distinguish between PBC and CAH; (2) in presymptomatic PBC the negativity of both methods is adequately compensated by a high frequency of characteristic bile duct lesions and granuloma formation: (3) the absence of orceinophilic intrahepatocytic granules, in our hands, does not accurately predict the response to steroid therapy.

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Anti-actin antibody was measured by the passive haemagglutination test in the serum of 118 patients with various forms of chronic cholestatic and non-cholestatic liver disease, and of 23 patients with acute hepatitis B or non-A, non-B. Tanned sheep erythrocytes and electrophoretically pure actin prepared from rabbit skeletal muscle were employed; absorption tests confirmed the specificity of positive reactions, defined from healthy controls as a titre of greater than 1/80. The presence of anti-actin activity in chronic liver disease corresponded generally to the immunofluorescent demonstration of smooth muscle antibody (P<0.01). However, in acute hepatitis, with one exception (later progressing to subacute disease) raised anti-actin titres were not found. Thus, the weak smooth muscle antibody occasionally demonstrable in this condition may be neither IgM in class, nor directed against actin. Anti-actin antibody was present in significantly high titre in 54% of 37 active chronic hepatitis patients and 79% of 24 ;mixed-form' cholestatic active chronic hepatitis, as compared with only 21% of 29 primary biliary cirrhosis patients, and 11% of alcoholic liver disease. Anti-actin antibody is therefore associated with chronic autoimmune parenchymal liver damage and its appearance may mark the transition from acute hepatitis. No raised anti-actin titres were seen in 10 primary biliary cirrhosis patients positive for mitochondrial antibody by indirect immunofluorescence, but negative by the complement fixation test. This result suggests that the cytoplasmic fluorescence observed is due to low titre mitochondrial antibody rather than cytoplasmic actin and that these patients do not represent a different disease entity. The generation of anti-actin antibody in chronic parenchymal liver disease, perhaps due to unmasking or schlepping of intracellular or SIg/HLA-associated actin, may characterise autoimmune events at hepatocyte level, point to prognosis, and aid in the differential diagnosis of individual patients.

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Anti-lipid-A, anti-endotoxin, antibodies have been measured by a passive haemolysis test using antigen from an E. coli Re mutant. Titres in the normal population are low but do rise in situations in which there has been gram-negative sepsis. Absence of raised titres in other situations has profound implications.

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An enzyme temporarily depressed by alcohol ingestion, erythrocyte delta-aminolaevulinate dehydratase (delta-ALAD), was compared with afternoon casual blood ethanol and plasma gamma-glutamyltransferase (gamma-glutamyltransferase (gamma-GT) simultaneously measured in outpatients. These comprised 37 individuals with chronic alcoholism, of whom 14 had severe liver disease, 22 patients with non-alcoholic liver disease and 24 healthy control subjects. All tests distinguished poorly between those alcoholics with, and those without histological liver damage. The highest specificity for alcoholism was achieved by gamma-ALAD; the best overall performance, with highest sensitivity and specificity was, however, gamma-GT. Although there was no correlation between the results of tests in individuals, 32/37 (87%) of alcoholics had at least one of the three tests abnormal compared with 8% of controls and 64% of non-alcoholic liver disease patients. The tests are therefore complementary and may form a battery of tests for problem drinking and its physical consequences.

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In a regional survey of paracetamol overdose, 201 patients were admitted to hospital over 12 months. Chronic alcoholism was present in 10% of cases. Over 25% of patients were females aged 20 years or less. Initial blood paracetamol levels were in the toxic range in 16% and histologically severe liver damage eventually found in 20% of those biopsied. This finding corresponded to a serum aspartate aminotransferase of 600 i.u./l or more. Renal failure severe enough to require peritoneal dialysis developed in 1%. Elevated serum amylase was recorded in 22% of a 108-patient subset. Evidence of myocardial damage was found in 11.6% of an eighty-six patient subset. An unfavourable prognosis was indicated by a prothrombin ratio of 20% or less and hepatic coma, the overall mortality being 3.5%. The apparent safety of this useful analgesic is compromized by its widespread employment in parasuicide. This, the insidious and delayed onset of toxicity in overdose and ineffectiveness of late treatment argues for controlling availability to the general public.

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