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Biomedical subjects

S Sherlock

Publications and source records attributed to S Sherlock.

At least 217 records · Page 12Linked to original sources

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.

Autoimmune Diseases↗

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.

Acute Kidney Injury↗

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.

Adult↗

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.

Adult↗

Effect of oral 1,25 dihydroxycholecalciferol on calcium and phosphate malabsorption in primary biliary cirrhosis.

Changes in calcium and phosphate absorption in response to treatment with small doses of oral 1,25 (OH)2D3 were studied in 10 patients with primary biliary cirrhosis by means of a combined radio-isotope technique. There was a marked improvement in the fractional rates of absorption of calcium (P less than 0.01) and phosphate (0.05 P less than 0.1) after treatment. This implies than there is no end organ unresponsiveness to the action of active Vitamin D metabolites at the intestinal level in primary biliary cirrhosis.

Administration, Oral↗

Monomeric (7S) IgM in chronic liver disease.

Monomeric (7S) IgM was detected by polyacrylamide/agarose gell immunodiffusion and Sephadex G200 gel filtration in 33% of sera from patients with primary biliary cirrhosis (PBC) and 5% of patients with HBsAg-negative chronic active liver disease (CALD). It was not found in the sera of patients with extrahepatic cholestasis, alcoholic liver disease (ALD), HBsAg-positive CALD and normal control subjects. In the PBC group the presence of 7S IgM was associated with significantly higher IgM concentrations and Clq binding activity (P less than 0.001; P less than 0.01 respectively). The antibody specificity of the 7S IgM is unknown. Its presence in patients with high serum IgM concentrations probably reflects failure of complete polymerisation of 7S IgM because of an increased rate of synthesis of the protein. The association of the presence of 7S IgM and high total IgM with immune complexes suggests that the increased rate of synthesis of IgM and formation of immune complexes probably are a result of the same antigenic (or mitogenic) stimulus.

Cholestasis↗

Effects of spontaneous portal-systemic shunting on insulin metabolism.

Insulin degradation was measured by the C-peptide/insulin ratio in 19 patients with portal vein block with extensive spontaneous portal-systemic shunting but minimal liver cell damage: 13 patients with biopsy-proved cirrhosis and 12 controls. Blood obtained fasting and for 3 hr after oral glucose was assayed for glucose, insulin, and C-peptide. Fasting C-peptide and insulin levels in patients with portal vein block and those in controls did not differ. Eight of 13 cirrhotic patients had fasting hyperinsulinemia with a significantly reduced C-peptide/insulin ratio. After glucose administration, the C-peptide/insulin ratio in portal vein block patients with normal aspartate transaminase levels did not differ from control values. In portal vein block patients with elevated asparatate transaminase levels, the C-peptide/insulin ratio was significantly reduced only from 60 min onwards. All the cirrhotic patients showed a significantly reduced C-peptide/insulin ratio after glucose administration. It is suggested that portal-systemic shunting of blood in the presence of a normal liver does not influence hepatic insulin metabolism and that the hyperinsulinemia of cirrhosis is a feature of parenchymal liver damage. In addition, insulin degradation was abnormal in all cirrhotic patients at high insulin secretion rates, even when fasting insulin levels were normal.

Adolescent↗

The aetiology, presentation and natural history of extra-hepatic portal venous obstruction.

Extra-hepatic obstruction of the portal vein is a well known cause of hypertension in childhood and 55 out of the 97 patients (57 per cent) seen with this condition presented before they were 15 years old. However, nearly half our cases (43 per cent) presented in adult life. Haematemesis was the commonest mode of presentation in both the adult and childhood group although splenomegaly was common, especially in the children. The severity and frequency of haematemesis increased during puberty in the children. Twelve children and three adults have now not bled for between five and 30 years, 10 of them ceasing spontaneously and five following surgery. Intra-abdominal infection or septicaemia precipitated the portal venous obstruction in 38 patients (39 per cent), though the exact cause of such obstruction in patients who had no cirrhosis was obscure in about half the cases. Ascites was present in 18/51 (35 per cent) of the children and 24/35 (69 per cent) of the adults. Its presence was associated with an increased mortality (p less than 0.01). Nineteen out of 42 (45 per cent) patients with ascites also had portal-systemic encephalopathy. Twenty-four patients died, nine having presented during childhood, variceal haemorrhage was responsible for death in 19 and infection in five. Sixty-four patients underwent 114 operations for variceal haemorrhage. Mortality was greater in the surgical group compared with those managed conservatively. Surgery is therefore indicated only in the rare case where bleeding cannot be controlled by medical means.

Adolescent↗

HBsAg-positive chronic liver disease: inhibition of DNA polymerase activity by vidarabine.

Four patients who had chronic liver disease and were positive for hepatitis B surface antigen (HBsAg) were treated with vidarabine, a synthetic purine nucleoside that inhibits DNA polymerase activity in vitro and in vivo. Before treatment all had raised serum DNA polymerase concentrations. Three also had hepatitis B e (HBe) and were shown by electron microscopy to have hepatitis B virus (Dane) particles in their serum. In all patients 10 days' treatment with vidarabine resulted in an immediate loss of DNA polymerase activity. In three patients the activity returned when treatment was stopped. In those three patients Dane particles and HBe antigen persisted during and after treatment; in the fourth patient, who remained negative for DNA polymerase, HBsAg titres fell. Although vidarabine inhibited virus replication, virus particles did not disappear from the blood in these patients, presumably because the particles were cleared only slowly. Similar results with interferon suggest that the virus disappears, and HBsAg titres fall, some weeks after the fall in DNA polymerase activity. Continued treatment may therefore have a sustained effect on viral replication. Whether vidarabine can permanently clear HBsAg and so arrest chronic liver disease remains to be seen, but at the very least it could reduce the spread of infection.

Adult↗

Immunosuppressive therapy in chronic liver disease.

Immunosuppressive treatment with prednisolone and/or azathioprine has been assessed in three chronic liver diseases with immunological features, namely chronic active hepatitis, cryptogenic cirrhosis and primary biliary cirrhosis. In chronic active hepatitis, controlled prospective clinical trials have shown clinical, biochemical and hepatic histological improvement when prednisolone with or without azathioprine is employed. Azathioprine alone has no advantage over placebo tablets. Cirrhosis is probably not prevented. Selection of patients for treatment, the response and therapeutic regimes are discussed. Patients with hepatitis B surface antigen positive chronic active hepatitis have a worse therapeutic response than those patients with chronic active hepatitis who are HBsAg negative. In primary biliary cirrhosis, corticosteroid treatment is contra-indicated on account of bone thinning. Azathioprine has been used in controlled clinical trials and is of only marginal benefit.

Azathioprine↗

Halothane hepatitis.

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Anesthesia, Inhalation↗

Phosphate metabolism in chronic liver disease.

Phosphate metabolism was investigated in 26 patients with a spectrum of liver diseases and mean fasting plasma phosphate concentrations were in the low normal range. A standard oral load of phosphate was used to test absorption and was subnormal in the majority of patients with large bile-duct obstruction and alcoholic liver disease. Subnormal results were also seen in patients with primary biliary cirrhosis and cirrhosis secondary to chronic active hepatitis. These abnormalities appeared to be related to vitamin-D deficiency. Tubular reabsorption of phosohate was markedly reduced in 3 of 14 patients. The therapeutic implications of phosphate status in liver disease are important.

Absorption↗

Induction of remission in hepatocellular carcinoma with doxorubicin.

Doxorubicin (60 mg/m2 at 3-weekly intervals to a maximum total of 550 mg/m2) induced clinical remission in 14 (32%) of 44 patients with hepatocellular carcinoma. In 3 of those who responded, hepatic arteriography showed clearing of the previously extensive tumour circulation, and in a 4th there was disappearance of the tumour on serial ultrasound examinations. A fall in serum-alpha-fetoprotein level after the initial injection of doxorubicin predicted a favourable clinical response, whereas the level continued to rise in patients who did not respond.

Adult↗

Formation of vitamin D metabolites from 3H- and 14C-radiolabelled vitamin D-3 in chronic liver diseases.

Four of the eight patients studied were vitamin D replete and 4 vitamin D depleted as judged by serum 25-hydroxy vitamin D (25-OHD) concentration. Three of the 4 vitamin D depleted patients (including 2 with histological osteomalacia) formed radioactive 1,25-dihydroxycholecalciferol. One of the four vitamin D replete patients formed 1,25-dihydroxycholecalciferol but all formed 24,25-dihydroxycholecalciferol. This study suggests that patients with liver disease form dihydroxy vitamin D metabolites in an appropriate manner.

Adult↗