Biomedical subjects
P R Powell-Jackson
Publications and source records attributed to P R Powell-Jackson.
Ultrasound scanning and 99mTc sulphur colloid scintigraphy in diagnosis of Budd-Chiari syndrome.
Ultrasound scanning and 99mTc sulphur colloid scintigraphy are widely used in the diagnosis of the Budd-Chiari syndrome and have been compared at the time of presentation in 18 patients in whom the diagnosis was subsequently confirmed by histology and hepatic venography. Ultrasound was diagnostic in 16 (87%). The findings seen most often included hepatic vein abnormalities, caudate lobe hypertrophy with decreased reflectivity and compression of the inferior vena cava. Additional information not shown by scintigraphy included intracaval tumour, or thrombosis, and concomitant portal vein thrombosis. Although scintigraphic abnormalities were present in all patients, only in three (17%) was the 'classical' appearance of increased uptake and/or enlargement of the caudate lobe present. In one patient with nonspecific abnormalities on ultrasound, scintigraphy gave a positive diagnosis and it is in such cases that scintigraphy should continue to be used.
Budd-Chiari syndrome presenting as fulminant hepatic failure.
Two cases of the Budd-Chiari syndrome are described in whom the diagnosis was finally confirmed at necropsy. The presentation was with encephalopathy, occurring within eight weeks of first symptoms and coming therefore within the definition of fulminant hepatic failure. In one, thought to have non-A, non-B hepatitis, encephalopathy progressed to grade 4 coma with death 12 days after presentation. In the other, mistakenly thought to have intra-abdominal malignancy, an exploratory laparotomy exacerbated the encephalopathy with death three weeks later. In neither case were non-invasive investigations, such as ultrasound and isotope scanning, carried out which might have facilitated an earlier diagnosis and consideration for orthotopic liver transplantation, probably the most appropriate form of therapy for these very severe cases.
Convulsions associated with cyclosporin A in transplant recipients.
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Effect of rifampicin administration on theophylline pharmacokinetics in humans.
Theophylline pharmacokinetics were studied before and after rifampicin administration (600 mg daily for 1 wk). Rifampicin reduced the area under the concentration-time curve by 18% after the oral administration of sustained release aminophylline (450 mg) to 7 normal subjects (p less than 0.05) and increased the metabolic clearance and volume of distribution by 45% (p less than 0.05) and 17% (p less than 0.05), respectively, after the intravenous administration of aminophylline (5 mg/kg over 30 min) to 8 normal subjects. These findings are consistent with an inducing and choleretic effect of rifampicin on theophylline disposition. In patients receiving theophylline, blood levels should be monitored closely and dosage adjusted if rifampicin therapy is introduced or withdrawn.
Adult respiratory distress syndrome and convulsions associated with administration of cyclosporine in liver transplant recipients.
A "capillary leak" syndrome resulting from cyclosporine-induced membrane toxicity has been postulated as the cause of convulsions and pulmonary edema in bone marrow transplant recipients. We describe here the occurrence of similar complications in a group of 21 adults receiving liver transplants since July 1982. Of 12 patients treated with i.v. cyclosporine (4 mg/kg/day), 2 developed an adult respiratory distress syndrome (ARDS) within five days of the operation, but it was not found in those given prednisolone (0.05-1.0 mg/kg/day) and azathioprine (1.0 mg/kg/day). ARDS only occurred when cyclosporine was administered through a central vein, and therefore might be related to high concentrations of cyclosporine reaching the pulmonary circulation and causing damage to vascular membranes. Convulsions occurred in one patient given i.v. cyclosporine, and in three when therapy was changed and cyclosporine and corticosteroids were used in combination. Convulsions did not occur inthe same patients as ARDS, were not part of a generalized "capillary leak" syndrome, and were not associated with hypertension or renal failure, as reported elsewhere in children. Fluid retention consequent on cyclosporine administration aggravated by the use of corticosteroids appears to be the most likely explanation of the convulsions.
Hepatotoxicity to sodium valproate: a review.
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Nephrotoxicity of parenterally administered cyclosporine after orthotopic liver transplantation.
The frequency of nephrotoxicity in the absence of identifiable prerenal or postrenal causes within five days of operation in 27 liver transplant recipients was found to be 71% in those treated with i.v. cyclosporine alone, 37.5% with i.m. cyclosporine alone, and 16.7% with prednisolone and azathioprine. Renal failure following i.v. cyclosporine was characterized by an immediate fall in urine output and creatinine clearance with well-preserved tubular function--findings consistent with a reduction in renal blood flow or glomerular filtration rate, or both.
Adverse effect of rifampicin administration on steroid-dependent asthma.
Induction of steroid metabolism has been reported after rifampicin administration but it is not known how much corticosteroid requirements increase and whether disease control can be satisfactorily maintained with increases in corticosteroid dosage. Because rifampicin may be needed in the treatment of tuberculosis in patients with steroid-dependent asthma, the dose of prednisolone needed to control this condition after rifampicin administration (600 mg daily for 6 wk) was determined in 6 patients in a randomized, double-blind, placebo-controlled trial. The plasma elimination half-life and bioavailability of prednisolone decreased significantly after rifampicin administration, but despite an increase of 93% in the dose of prednisolone (p less than 0.02), asthma control remained inferior compared to placebo. Asthma relapse in a seventh patient necessitated withdrawal from the trial after 2 wk of rifampicin administration despite a five-fold increase in prednisolone dosage. It is concluded that despite substantial increases in the dose of prednisolone the coadministration of rifampicin and prednisolone to steroid-dependent patients may seriously complicate their clinical management.
Effect of isoniazid administration on selected rat and mouse hepatic microsomal mixed-function oxidases and in vitro [14C]acetylhydrazine-derived covalent binding.
The effect of isoniazid on selected microsomal mixed-function oxidase activities and on the microsomal metabolism of its own metabolite, acetylhydrazine, to a highly reactive compound which covalently binds to intracellular macromolecules was characterized in male C57BL6 mice and male Sprague-Dawley rats. In comparison with controls, isoniazid pretreatment of rats significantly increased the sp. act. of acetanilide 4-hydroxylase and the in vitro [14C]acetylhydrazine-derived covalent binding to hepatic microsomes but significantly decreased the sp. act. of benzo[a]pyrene hydroxylase and testosterone 16 alpha-hydroxylase. Isoniazid treatment of mice had no effect on any of these parameters except for a significant reduction in sp. act. of testosterone 7 alpha-hydroxylase. Thus the pathway of isoniazid metabolism leading to the formation of reactive metabolites of acetylhydrazine is enhanced by isoniazid pretreatment in rats but not in mice. The presence of similar routes of isoniazid metabolism in man may account for the 8.7-24% incidence of subclinical hepatocellular damage observed in patients receiving isoniazid alone in the chemoprophylaxis of tuberculosis.
Accelerated development of alcoholic cirrhosis in patients with HLA-B8.
To test whether the increased prevalence of HLA-B8 reported in patients with alcoholic cirrhosis is due to the antigen being a genetic marker of susceptibility to liver damage from alcohol, patients who had cirrhosis of comparable clinical and histological severity were investigated for HLA-B8 status and cumulative alcohol intake. Both male and female cirrhotics with HLA-B8 had been drinking greater than 40 g alcohol/day for a shorter period of time (16.6 +/- 1.4 men, and 9.4 +/- 2.0 years, women) than their counterparts without this antigen (23.7 +/- 1.7, p less than 0.005, and 15.8 +/- 2.0 years, p less than 0.05, respectively), but the mean daily alcohol intake was similar whether patients had HLA-B8 or not. These results suggest that genetic determinants linked to HLA-B8 enhance the rate of development of liver damage in those who drink potentially hepatotoxic amounts of alcohol.
Budd-Chiari Syndrome: clinical patterns and therapy.
Retrospective analysis of 36 patients (25 women, 11 men) with the Budd-Chiari syndrome diagnosed between 1971 and 1980 showed a wide range in aged at presentation (12 to 68 years) with the peak incidence in the third decade for women and in the fourth for men. The 11 patients below the age of 30 were women and six of these had been taking oral contraceptive preparations. There was also a wide range in duration of illness before establishment of diagnosis ranging from eight weeks or less in 20 patients, to up to six years in the other 16. Those in the former group had a high incidence of the 'classical' clinical features (tender hepatomegaly with ascites) and most severe abnormalities in liver function tests. Liver scintiscanning showed the characteristic pattern of maximum colloid uptake in the caudate lobe in only 46 per cent of patients. Mistaken diagnosis in eight cases led to early exploratory laparotomy with serious deterioration in four. One year survival of 58.3 per cent was unrelated to age, sex, or aetiology and little benefit was seen in the few cases treated early with fibrinolytic agents. Of the surgical measures employed only hepatic transplantation has proven worthwhile with three out of four cases alive at 14, 16 and 52 months respectively from the time of operation.
Effect of rifampicin on the mouse hepatic mixed-function oxidase system.
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Use of liver function tests as predictors of rifampicin metabolism in cirrhosis.
Normal subjects taking rifampicin regularly, show a fall in serum and urinary drug concentrations from enzyme induction and increased biliary excretion. In cirrhosis, hepatocellular dysfunction and impaired biliary excretion may prevent these changes, but there is little information on how the drug should be prescribed in such patients. Serum and urinary rifampicin concentrations were therefore measured in thirteen patients and five controls during a seven-day course (600 mg/day). In controls, peak serum concentrations on Day 7 were lower than on Day 1 (7.0 +/- 3.0 and 8.0 +/- 1.0 microgram/ml respectively) and this was also the case for nine cirrhotic patients with mild impairment of liver function (6.0 +/- 1.0 and 11.0 +/- 2.0 microgram/ml (p less than 0.02). In both groups there was an accompanying fall in urinary rifampicin excretion due to a decrease in desacetylrifampicin excretion. In the remaining four cirrhotic patients, peak serum rifampicin levels rose from 11.0 +/- 5.0 to 17.0 +/- 6.0 microgram/ml and urinary excretion of desacetylrifampicin did not fall. Although values for serum albumin and prothrombin time were of limited value in predicting drug accumulation, pretreatment levels of bilirubin exceeding 50 mumol/l were present in all four patients showing an increase in serum rifampicin concentration. Furthermore, only in this group was there a rise in serum bilirubin during treatment, almost certainly the result of competition between rifampicin and bilirubin for hepatic uptake and excretion. In all patients with cirrhosis, bilirubin concentrations exceeding 50 mumol/l should be an indication for reduction of rifampicin dosage.
Intestinal bacterial metabolism of protein and bile acids: role in pathogenesis of hepatic disease after jejuno-ileal bypass surgery.
Jejunal bacterial colonization and intestinal metabolism of bile acids and protein by bacteria have been investigated in 12 patients with abnormal liver histology following jeujno-ileal bypass surgery for obesity. Aerobic and/or anaerobic colonic flora was present in jejunal aspirates from 8 of 12 bypass patients, but in none of the controls. Intestinal protein metabolism and bile acid deconjugation (measured by urinary indican excretion and 14C-glycocholic acid breath test) was significantly enhanced in bypass patients. Intestinal bacterial overgrowth, with abnormal intestinal metabolism by bacteria of ingested nutrients and bile acids, could contribute to hepatic disease after bypass surgery via the production of endogenous hepatotoxins.
Interaction between azapropazone and warfarin.
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Excess deoxycorticosterone secretion from adrenocortical carcinoma.
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Fluoride, water hardness, and endemic goitre.
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