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Biomedical subjects

S Sherlock

Publications and source records attributed to S Sherlock.

At least 145 records · Page 8Linked to original sources
PubMed1982

Chronic intrahepatic cholestasis due to sarcoidosis.

Two West Indian patients with Kveim-biopsy proven sarcoidosis developed chronic cholestatic liver disease, clinically and biochemically similar to primary biliary cirrhosis. Liver histology revealed multiple granulomas with reduction in bile ducts and, in one patient, progression to biliary cirrhosis. Portal hypertension was present in both patients leading to severe variceal haemorrhage in one. Mitochondrial antibody was negative in both patients and when used in conjunction with the Kveim-Siltzbach skin test serves to differentiate chronic intrahepatic cholestasis secondary to sarcoidosis from primary biliary cirrhosis.

Biopsy↗
PubMed1982

Effects of prednisolone/azathioprine in chronic hepatitis B viral infection.

Changes in markers of hepatitis B viral replication and standard liver function tests were studied in 30 patients with HBsAg positive chronic liver disease starting or stopping prednisolone/azathioprine therapy, and compared with those occurring in 15 patients who did not receive therapy. On stopping prednisolone/azathioprine, 10 out of 11 HBeAg positive patients and one out of three patients negative for HBeAg and anti-HBe, lost HBV-DNA polymerase activity (p less than 0.01), five lost HBeAg, three developed anti-HBe and HBsAg concentration decreased (p less than 0.01). Only one out of seven untreated HBeAg positive patients lost HBeAg and there were no significant changes in DNA polymerase activity. In the anti-HBe positive patients, 14 starting therapy and eight untreated, there were no significant changes in the markers of viral replication - although two patients developed DNA polymerase activity on high maintenance doses of prednisolone - but a significant decrease (p less than 0.05) in aspartate transaminase in the treated group. It is concluded that the cessation of prednisolone/azathioprine therapy in HBeAg positive patients will result in a reduction in viral replication. In anti-HBe positive patients such therapy may be beneficial.

Azathioprine↗
PubMed1982

Successful treatment of HBs and HBeAg positive chronic liver disease: prolonged inhibition of viral replication by highly soluble adenine arabinoside 5'-monophosphate (ARA-AMP).

In eight HBs and HBe antigen positive patients with chronic active liver disease, adenine arabinoside 5'-monophosphate (ARA-AMP) given, intravenously or intramuscularly, six or 12 hours, produced inhibition of viral replication. In five patients given a short course of therapy with 10 or 15 mg/kg/day this effect was transient and in two thrombocytopenia occurred. In three further consecutive cases given a longer course with 5 mg/kg/day after five days of the high dose, thrombocytopenia was not seen and inhibition of viral replication for up to 13 months occurred. These patients lost HBV-DNA polymerase activity, serum viral DNA and HBeAg, developed anti-HBe, and HBsAg concentrations decreased. A course of twice daily intramuscular ARA-AMP given for three to five weeks as an outpatient may be expected to produce a long-term reduction in infectivity.

Adult↗
PubMed1982

Serum glutamate dehydrogenase is not a reliable marker of liver cell necrosis in alcoholics.

Serum glutamate dehydrogenase (EC 1.4.1.3.) activity was measured in 73 hospital patients who had a history of chronic alcohol abuse and who all had a liver biopsy performed. High levels of serum GDH activity occurred in those patients with recent excess alcohol consumption independently of the underlying liver histology, and did not discriminate between those patients with and those without alcoholic hepatitis.

Ethanol↗
PubMed1982

Binding of serum ferritin to concanavalin A in patients with iron overload and with chronic liver disease.

Total serum ferritin and the proportion of serum ferritin binding to concanavalin A (glycosylated ferritin) was measured in 18 healthy volunteers and in 84 patients, eight with primary haemochromatosis, 43 with beta-thalassaemia major and secondary iron overload and 33 with chronic liver diseases without iron overload. The total serum ferritin was either equally or even more closely related than either the non-binding or the concanavalin A binding ferritin, to the liver iron concentration in all patients with iron overload, and with the units of blood transfused in non-chelated thalassaemic patients. The total serum ferritin showed a significant correlation with serum aminotransferase for the group of 84 patients. In the thalassaemic patients the ferritin binding to concanavalin A also correlated with aminotransferase. However, in the other groups it was the ferritin not binding to concanavalin A which showed a significant correlation with aminotransferase activity. These results suggest that measuring the fraction of serum ferritin which binds to concanavalin A does not offer any advantage over estimation of the total serum ferritin concentration in the assessment of iron stores in patients wit iron overload and liver damage.

Binding Sites↗
PubMed1982

Effect of ascorbic acid deficiency on serum ferritin concentration in patients with beta-thalassaemia major and iron overload.

The incidence of ascorbic acid (AA) deficiency and its effect on serum ferritin concentration relative to body iron stores was studied in 61 unchelated patients with beta-thalassaemia major. Thirty-nine (64%) of patients had subnormal leucocyte ascorbate concentrations without clinical evidence of scurvy. The lowest leucocyte ascorbate concentrations tended to occur in the most transfused patients. No correlation was found between the units transfused and serum ferritin concentration in the AA-deficient patients but a close correlation (r = +0.82; p less than 0.005) existed for the AA-replete group. Similarly a close correlation (r = +0.77; p less than 0.005) was obtained between liver iron concentration and serum ferritin in AA-replete patients but only a weak correlation (r = +0.385; p less than 0.025) existed for the AA-deficient group. When AA-deficient patients were treated with ascorbic acid, serum iron and percentage saturation of iron binding capacity rose significantly; serum ferritin rose in 13 of 21 patients despite the simultaneous commencement of desferrioxamine therapy. In contrast all three measurements tended to fall in AA-replete patients with ascorbic acid and desferrioxamine therapy. Thus, AA deficiency is commonly present in beta-thalassaemia patients with iron overload and may give rise to inappropriate serum ferritin concentrations in relation to body iron stores.

Adolescent↗
PubMed1982

Guillain-Barré syndrome associated with hepatitis A in a male homosexual.

A 48-year-old male homosexual developed the Guillain-Barré syndrome in association with acute hepatitis. The hepatitis A virus was almost certainly transmitted sexually. Since the incidence of viral hepatitis is high in active male homosexuals, they are particularly at risk of developing such complications.

Hepatitis A↗
PubMed1982

Primary biliary cirrhosis: critical evaluation and treatment policies.

Primary biliary cirrhosis is a disease where small intra-hepatic bile ducts are destroyed as a result of an immunological reaction, presumably by cytotoxic T-lymphocytes on biliary epithelium. Analogies can be made to the graft-versus-host reaction. Hepatic copper retention is secondary to cholestasis. A circulating mitochondrial antibody is virtually constant. A mitochondrial antibody, specific for primary biliary cirrhosis, has been identified. Liver biopsy appearances have been staged but there are difficulties because of the varying rte of evolution in different parts of the liver, the focal nature of the changes and the lack of correlation with the clinical picture. Other diagnostic criteria include female sex, raised serum alkaline phosphatase values and various associated diseases. Many patients are now diagnosed when presymptomatic and such patients, particularly with granulomas in the liver, may have a normal life expectancy. General therapeutic measures include control of pruritus and prevention of fat soluble vitamin and calcium deficiencies. There is no specific treatment but D-penicillamine is useful in the later stages and prolongs survival. The prognosis in those with progressive jaundice is very poor.

Adrenal Cortex Hormones↗
PubMed1982

The pancreas in primary biliary cirrhosis and primary sclerosing cholangitis.

In patients with primary biliary cirrhosis, the chronic cholestasis, salivary, and lacrimal hyposecretion suggest that the disease is a "dry gland" syndrome. To determine whether or not pancreatic damage occurs in primary biliary cirrhosis and other forms of chronic cholestasis, we have studied pancreatic structure and function in primary biliary cirrhosis, and primary sclerosing cholangitis. In a retrospective study, retrograde pancreatograms were abnormal in 43% of 35 patients with primary biliary cirrhosis and 15% of 20 patients with primary sclerosing cholangitis (p less than 0.02). In a prospective study, serum pancreatic isoamylase was abnormal in 56% of 41 patients with primary biliary cirrhosis and 36% of 22 patients with primary sclerosing cholangitis (NS), indicating pancreatic damage in both diseases. After secretin-pancreozymin stimulation, patients with primary biliary cirrhosis, but not patients with primary sclerosing cholangitis, showed a significant reduction in duodenal juice flow rate (p less than 0.01) and immunoreactive trypsin output (p less than 0.01). The reduced trypsin output in patients with primary biliary cirrhosis indicates pancreatic hyposecretion. In neither patients with primary biliary cirrhosis nor patients with primary sclerosing cholangitis was the immunoreactive trypsin concentration, or tryptic activity in duodenal juice, significantly different from controls. Pancreatic involvement in primary biliary cirrhosis is closely associated with Sjogrens syndrome, and it is likely that the pancreatic hyposecretion is a component of the sicca complex. This association was not obvious in primary sclerosing cholangitis.

Cholangitis↗
PubMed1981

D-penicillamine treatment improves survival in primary biliary cirrhosis.

The copper-chelating, immunological, and antifibrotic effects of D-penicillamine indicated that it might be suitable for the treatment of primary biliary cirrhosis (PBC). In a randomised clinical trail, 55 PBC patients received penicillamine (600 mg daily), and 32 received a placebo. Drug reactions developed in 16 patients on penicillamine. All deaths occurred in patients with stage 3 or 4 (late stage) liver histology on entry to the study. 5 (14%) of 37 penicillamine-treated patients and 10 (43%) of 23 placebo patients have died (p less than 0.01). Improvement in survival only became evident after 18 months. Survivors in the penicillamine group demonstrated a significant fall in serum aspartate transaminase, serum immunoglobulins, and liver copper concentrations. On follow-up liver biopsy 12-72 months (median 33) after joining the study, 21% of penicillamine-treated patients had less pronounced inflammation and piecemeal necrosis, whereas there had been no improvement in patients on placebo (p less than 0.02). Penicillamine did not retard the histological evolution of the liver disease from the early prefibrotic stages to the late fibrotic or cirrhotic stages. Both the copper-chelating and immunological effects of penicillamine are probably important in improving survival. The excellent prognosis of patients with PBC in its early histological stages, and the failure of penicillamine to prevent histological progression from early to late stages, suggests that penicillamine treatment should not be given to patients with PBC in the early (stage 1 or 2) histological phase of the disease. Penicillamine treatment is recommended in patients once liver biopsy has demonstrated histological results typical of late stage 3 or 4 PBC.

Antigen-Antibody Complex↗
PubMed1981

Is Wilson's disease caused by a controller gene mutation resulting in perpetuation of the fetal mode of copper metabolism into childhood?

Wilson's disease is an inborn error of copper metabolism, characterised by raised liver-copper concentrations and low serum levels of copper and caeruloplasmin. The autosomal recessive mode of inheritance strongly suggests that mutation of a single gene causes the impairment of both caeruloplasmin synthesis and biliary copper excretion. The normal infant is born with the biochemical features of Wilson's disease (very high liver-copper levels and low serum copper and caeruloplasmin). Induction of normal copper metabolism after birth results in a fall in liver-copper concentrations and rise in serum caeruloplasmin. The repression of normal copper metabolism in the fetus and its induction after birth is probably regulated by a controller gene. It is suggested that mutation of a controller rather than a structural gene underlies the pathogenesis of Wilson's disease and that the disease results from failure to switch from the positive copper balance of the fetus to the normal copper balance of the child.

Carrier Proteins↗
PubMed1981

Ultrastructural features in chronic non-A, non-B (NANB) hepatitis: A controlled blind study.

Liver biopsies from 12 patients with chronic Non-A, Non-B (NANB) hepatitis, 7 with hepatitis B surface antigen (HBsAg) positive chronic liver disease, 1 HBsAg positive normal carrier, and 4 patients with non-viral liver disease, were examined by electron microscopy for cytoplasmic and nuclear changes. Aggregates of particles measuring 20-35 nm in diameter were noted in the nuclei of 8 of 12 patients with NANB chronic hepatitis, but not in the other groups. The tubular changes seen in the endoplasmic reticulum (ER) of chimpanzees with NANB hepatitis were not noted in biopsies from any of our patients.

Cell Nucleus↗
PubMed1981

Long-standing asymptomatic primary sclerosing cholangitis: report of three cases.

Three patients, two males and one female, with asymptomatic primary sclerosing cholangitis (PSC) are described. The diagnosis was made in each case by endoscopic retrograde cholangiography after investigation of persistent elevation of the serum alkaline phosphatase. All three have remained completely well without any medical or surgical treatment for 3, 7, and 15 years, respectively, despite extensive involvement of the biliary tree. Follow-up liver biopsies in two have shown no histological evidence of progression to secondary biliary cirrhosis. PSC may occur more frequently and may follow a less severe clinical course than previously recognized.

Adult↗
PubMed1981

Computed tomography attenuation values in fatty liver.

The accuracy of CT diagnosis of increased fat deposition in the liver was assessed in 11 alcoholic patients with suspected fatty liver. Single-energy CT attenuation values were compared with histological assessment of fatty liver and chemical analysis of liver triglyceride concentrations, obtained from liver biopsy specimens. Measured attenuation values showed an inverse correlation with the degree of fatty change assessed histologically (r =--0.90; p Less Than 0.0001) and with that assessed chemically (r=--0.57; p Less Than 0.05). CT scanning may provide a useful non-invasive method for detecting and following patients with fatty liver, particularly when liver biopsy is contraindicated.

Adult↗
PubMed1981

Relief of bileduct obstruction by the percutaneous transhepatic insertion of an endoprosthesis.

Benign and malignant biliary strictures can be treated by the percutaneous transhepatic insertion of an endoprosthesis. We report the use of this technique in 44 patients, with a detailed description of the procedure. Insertion was successful in 41, three of whom later had elective surgery, and one, emergency laparotomy for biliary peritonitis. This patient died post-operatively. Cholestasis was relieved in 31 of the remaining 37 patients. Complications occurred in four. Twelve patients, all with malignant disease, died within 30 days of the procedure. The percutaneous insertion of a biliary endoprosthesis is a valuable alternative to surgery in selected patients. Complications can occur, and the prognosis depends on the nature of the underlying disease.

Adult↗