Biomedical subjects
S Sherlock
Publications and source records attributed to S Sherlock.
The pathology of hepatitis C.
To determine the histologic pattern of hepatitis C, 54 liver biopsy specimens from 45 patients with a clinicopathological diagnosis of hepatitis C were studied. All patients were seropositive for antibody to hepatitis C virus by second-generation testing. Both transfusion-related and sporadic cases were included. More than half the samples showed chronic hepatitis without cirrhosis, whereas 44% showed developing or fully established cirrhosis. A histological pattern of mild chronic hepatitis with portal lymphoid follicles and varying degrees of lobular activity was found in many of the patients. Lymphoid aggregates or follicles were seen in 78% of biopsy specimens, but aggregates, less prominent than in hepatitis C, were also seen in 14 of 27 samples (52%) from patients with hepatitis B. We conclude that a characteristic histological pattern exists in chronic hepatitis C, that this pattern is not always found and that prominent lymphoid follicles, though not unique to hepatitis C, provide a useful diagnostic clue.
Improved diagnosis of chronic hepatitis C virus infection by detection of antibody to multiple epitopes: confirmation by antibody to synthetic oligopeptides.
Serum samples from 226 patients covering a wide spectrum of liver disease were tested for antibodies to hepatitis C virus (HCV) using both first and second generation enzyme linked immunosorbent assays. Selected sera were also tested by peptide immunoassays, by the four-antigen recombinant immunoblot assay (RIBA II), and for viral genome by the polymerase chain reaction. Antibody to c100-3 was detected in 61% of patients with chronic non-A, non-B (NANB) hepatitis and/or 46.5% with presumed NANB-related cirrhosis by the first generation test. These figures increased to 77% and 58% when antibodies to recombinant structural and non-structural HCV antigens were sought by the second generation assay. Supplemental testing against peptide Sp75 and Sp65/sp67 confirmed that reactivity of sera by second generation assays was due to antibodies to the additional structural and non-structural antigens. Samples negative by the first generation assay were not confirmed by the supplemental assay using peptides Sp75 and Sp65/Sp67. HCV RNA was detected in 60% of the anti-HCV positive sera tested, most of which were also RIBA II positive. Our findings confirm that the introduction of the structural and non-structural antigens, especially the putative nucleocapsid protein, improves sensitivity of detection of antibodies to HCV, and facilitates diagnosis in patients with "cryptogenic" chronic hepatitis.
Jaundice--the first 48 hours.
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Non-surgical treatment of biliary obstruction.
Bileduct catheterisation percutaneously through the liver can be used in patients with obstructive jaundice as an adjunct or as an alternative to surgery. Preoperative drainage allows adequate treatment of severe cholangitis and reduces jaundice. Palliative drainage, whether internal or external, can be used instead of surgery. Drainage through the liver succeeded in 40 of 41 patients. Two complications followed the procedure and were treated conservatively. Bile drainage was established through an endoprosthesis into the duodenum in 7 patients and externally through a catheter in the remaining 33. The technique is described, and its use in patients with suppurative cholangitis and benign and malignant biliary strictures is illustrated.
[Halothane hepatitis].
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Reduction of immune complexes and immunoglobulins induced by D-penicillamine in primary biliary cirrhosis.
Penicillamine has an effect on immune complexes and immunoglobulins both in vivo and in vitro. We therefore studied the effect of penicillamine on immune complexes and immunoglobulins in primary biliary cirrhosis. Twenty-eight patients were randomly allocated into a treatment group receiving 600 to 900 mg of penicillamine, or a control group, and followed for a maximum of 24 months. After 12 and 24 months, serum immune complexes had fallen significantly in treated patients as compared to controls (P less than 0.05, P less than 0.01). Treatment reduced IgA, IgG and IgM concentrations, with IgM being significantly different from controls at six, 12 and 24 months (P less than 0.01). Over 24 months, serum aspartate transaminase levels fell in treated patients but rose in controls (P less than 0.01). Bilirubin concentrations increased at a slower rate in treated patients. Penicillamine may favorably influence the course of primary biliary cirrhosis by its immunologic action in addition to its copper-chelating action.
Primary liver cell cancer in Britain--a viral aetiology?
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Hepatic siderosis in alcoholics.
In a population of 157 (120 males, 37 females) predominantly British alcoholics with liver disease, the incidence of some degree of hepatic siderosis, as estimated by stainable parenchymal iron, was 57.3%. The incidence of significant siderosis (grades III and IV) was 7%, and was similar for both sexes. In the female alcoholics there was a significant correlation between age and the degree of siderosis (P less than 0.05)--four of the five females with significant siderosis being premenopausal. In the male alcoholics there was a significant inverse relationship between the grams of ethanol consumed per day and the degree of siderosis (P less than 0.05) and a significant correlation between the percentage saturation of iron-binding protein and the degree of siderosis (P less than 0.05). The mean daily iron intake from alcoholic beverages was 1.5 mg; there was no relationship between the amount of iron ingested in the alcohol and the degree of siderosis. In this population of alcoholics the incidence of significant siderosis in both sexes was low.
Renal hemodynamics and the renin--angiotensin system in cirrhosis: relationship to sodium retention.
Renal hemodynamics and the renin-angiotensin-aldosterone system were investigated in 15 cirrhotic patients without renal failure on controlled sodium intake of 140-160 mEq/day and related to the degree of sodium retention as measured by urinary sodium excretion. Fourteen patients were free of clinical ascites when studied. The distribution of renal blood flow was measured by the noninvasive technique of computerized radioisotope renography. In 11 patients, outer cortical renal plasma flow, expressed as a percentage of total effective renal plasma flow, was directly proportional to sodium excretion (P less than or equal to 0.01). Three patients with severe sodium retention (UNa.V less than or equal to 10 mEq) had estimated outer cortical renal plasma flows of less than or equal to 274 ml/min/1.73 M2 as compared to eight cirrhotics with better (UNa.V greater than or equal to 50 mEq) sodium tolerance (mean = 438 ml/min/1.73 M2). A significant inverse correlation (P less than or equal to 0.01) existed between outer renal cortical blood flow and plasma renin activity. No significant relationship was observed between glomerular filtration rate, total effective renal plasma flow, plasma aldosterone concentration and sodium excretion. These results provide further evidence that a renal vascular abnormality exists in cirrhosis, and that diminished outer cortical renal perfusion is related to the elevated renin levels and sodium intolerance observed in cirrhotic patients.
Hypertrophic hepatic osteoarthropathy. Clinical, roentgenologic, biochemical, hormonal and cardiorespiratory studies, and review of the literature.
Twenty patients with biopsy proved liver disease, and roentgenologic features of hypertrophic osteoarthropathy have been studied, and the literature has been reviewed. The syndrome is a rare association of many chronic liver diseases, including primary biliary cirrhosis, bile duct carcinoma, benign bile duct stricture, chronic active hepatitis, posthepatitic cirrhosis and alcoholic cirrhosis. Patients may be asymptomatic, although bone pain, arthralgia or arthritis may be presenting symptoms. Ninety per cent of the patients are clinical jaundiced at the time of diagnosis, and 95 per cent have digital clubbing. The distal tibia and fibula are the first bones to become involved, although wrist, foot bones, femurs, hand bones and humeri may be affected in order of frequency. There is no correlation between the presence of esophageal varices or surgical portacaval shunts and the extent of the syndrome, neither is there a correlation with the degree of liver function impairment. Serum calcium and phosphate levels are normal, as is urinary hydroxyproline and estrogen excretion. There was no evidence to implicate elevated levels of growth hormone or overdosage of vitamin A. Although the majority of patients tested had mild arterial hypoxemia, increased cardiac output and evidence of right to left shunting, these were also present in disease-matched control subjects without osteoarthropathy. For screening purposes, patients with chronic liver disease and clubbing should have roentgenologic studies of the lower tibias and fibulas, to select those patients suitable for a more extensive skeletal survey.
Factors affecting plasma amino acid concentrations in control subjects.
Plasma amino acid concentrations were determined in groups of normal control subjects under fasting and postprandial conditions. Differences were observed that were found to be, to a considerable extent, sex-related. Fasting females had lower concentrations than fasting males of several amino acids, although postprandial differences in concentrations between the sexes were not significant. Under the dietary conditions normal for a British population, no significant diurnal variation of plasma amino acid concentrations was found. Reducing the dietary protein by 30% failed to affect plasma amino acid concentrations; however, increasing the dietary protein by 50% resulted in a significant increase in the plasma concentrations of several amino acids, and induced a significant degree of variation throughout the day in six, proline, half-cystine, methionine, valine, leucine, and isoleucine. The importance of these results with regard to the interpretation of population mean values and disease diagnosis is discussed.
Chronic hepatitis.
Chronic hepatitis may be viral or "lupoid" or may be related to drug use, alcoholism, or Wilson's disease. This article outlines the routine and special laboratory investigations that are indicated when the presence of chronic hepatitis is suspected from symptoms referable to the liver or from biochemical or physical abnormalities in an asymptomatic patient. The importance of needle liver biopsy in diagnosis and in follow-up is emphasized. Special attention is given to the selection of patients for prednisolone therapy.
Acute renal insufficiency occurring during intravenous desferrioxamine therapy.
A patient of 14 years suffering from secondary haemosiderosis and thalassaemia major was treated with i.v. desferrioxamine in doses up to 3 g/d. Urine iron loss ranged from 46-158 mg/d. Despite improvement in cardiac and hepatic status the patient developed acute renal insufficiency of the pre renal type. The possible role of desferrioxamine in this complication is discussed. Desferrioxamine given s.c. or i.v. effects a marked urinary iron loss but its use may not be without significant complications.
Chronic persistent hepatitis: hepatitis B virus markers and histological follow-up.
Twenty-six untreated patients with chronic persistent hepatitis were followed prospectively for one to 17 years (mean 5.6 years). The patients developed no clinical features of chronic liver disease. Raised serum transaminase levels were usually, but not consistently, the only biochemical abnormality; gamma globulin values were normal. Serum markers of past or present hepatitis B infection were found initially in 14 patients: another two developed markers during their follow-up. Nine patients progressed to a mild or moderate chronic active hepatitis as shown by serial needle liver biopsies but there was no evidence of cirrhosis. This progression was not associated with any clinical or biochemical deterioration. Seven of these patients had presented with insidious symptoms, seven had serum markers of hepatitis B infection, and the four who were HBsAg positive had relatively lower serum HBsAg concentrations than did those patients who continued with chronic persistent hepatitis.
Intestinal absorption of cholecalciferol in alcoholic liver disease and primary biliary cirrhosis.
The intestinal absorption of (3H)cholecalciferol was studied in five patients with alcoholic liver disease, six patients with primary biliary cirrhosis, and 15 healthy subjects. The rate of appearance in plasma of (3H)cholecalciferol after oral ingestion and the subsequent appearance of (3H) polar metabolites in the alcoholic subjects were similar to those in the healthy subjects. In subjects with primary biliary cirrhosis the rate of appearance in plasma of (3H)cholecalciferol was significantly reduced. The rate of appearance of labelled polar metabolites of cholecalciferol was also lower in this group, suggesting that increased removal of labelled vitamin by conversion into more polar metabolites could not account for the reduced plasma (3H)cholecalciferol response. It is suggested that intestinal absorption of cholecalciferol is usually normal in alcoholic liver disease but impaired in primary biliary cirrhosis. Hepatic 25-hydroxylation is normal in alcoholic liver disease but may be defective in primary biliary cirrhosis.