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Biomedical subjects

L W Powell

Publications and source records attributed to L W Powell.

At least 199 records · Page 11Linked to original sources
PubMed1979

Early detection of idiopathic haemochromatosis: relative value of serum-ferritin and HLA typing.

A study of 18 unrelated families with idiopathic haemochromatosis (I.H.C.) was undertaken to define the relative values of HLA typing and serum-ferritin estimation in the early detection of the disease. Sharing of both HLA haplotypes with the proband indicated a high risk of I.H.C. in siblings; but HLA typing was of limited value in detecting affected offspring. Non-identical HLA indicated a low risk of I.H.C. in both siblings and offspring. The presence of HLA A3 was not clinically useful as a marker for I.H.C., since this antigen was also present in 40% of unaffected relatives. In contrast, the serum-ferritin concentration was elevated in 96% of patients with I.H.C. and in only 5% of unaffected relatives. HLA typing provides some indication of the risk of I.H.C. in first-degree relatives, but the combination of serum-ferritin, serum-iron, and transferrin saturation remains the most reliable screening regimen for early diagnosis of I.H.C.

Adolescent↗
PubMed1979

Drug metabolism in liver disease: activity of hepatic microsomal metabolizing enzymes.

The concentration of cytochrome P-450 and activities of the microsomal enzymes aryl hydrocarbon hydroxylase and ethylmorphine demethylase were measured in hepatic tissue obtained at biopsy from 69 patients. Antipyrine half-life (AP t1/2) was measured simultaneously as an in vivo marker of drug metabolism. Values for each index of the drug-metabolizing system varied greatly, but the mean values in groups of patients with mild hepatitis or inactive cirrhosis did not differ significantly from those of controls. Hepatic cytochrome P-450 content and aryl hydrocarbon hydroxylase activity were lower in patients with severe hepatitis or active cirrhosis than in controls, but ethylmorphine demethylase activity was unchanged in the patients. Drug ingestion was associated with enhancement of drug-metabolizing enzymes in all patients but those with severe liver disease; ethylmorphine demethylase activity was enhanced proportionately more than aryl hydrocarbon hydroxylase activity or cytochrome P-450 concentration. The observation that aryl hydrocarbon hydroxylase and ethylmorphine demethylase activities are influenced to a different extent by liver disease and also by drug ingestion indicates functional heterogeneity of the hepatic microsomal drug-metabolizing system in man. Correlations between t1/2 and hepatic drug oxidases were weak, even when allowance was made for variation in liver size. Thus, the rate of drug metabolism in vivo assessed by measuring AP t1/2 does not appear to be closely related to the activity of some hepatic drug-metabolizing enzymes.

Antipyrine↗
PubMed1979

Enhancement of hepatic drug metabolism by glutethimide in patients with liver disease.

A controlled study of the effects of glutethimide on antipyrine metabolism was performed to ascertain how patients with varying degrees of liver damage responded to microsomal enzyme inducing agents. The administration of 250mg glutethimide daily for one week resulted in significant enhancement of antipyrine metabolism in 4 patients with compensated cirrhosis and 5 patients with features of hepatic failure as well as 7 control subjects without liver disease. Even patients with very severe liver disease did undergo microsomal enzyme induction. Changes in antipyrine half-life after glutethimide were directly proportional to the original antipyrine half-life so that the greatest absolute alterations due to enzyme induction occurred in patients with the most severely impaired hepatic function. These results indicate that not only is antipyrine metabolism severely impaired in patients with liver failure, but elimination rates are markedly altered by enzyme inducing agents. Thus, although these results cannot be extrapolated to all inducers of hepatic microsomal enzymes nor to all drugs metabolized by microsomal oxidases, it is suggested that safe and effective management of drug therapy in these patients requires measurement of plasma levels.

Adult↗
PubMed1979

Concurrent administration of antacids and prednisone: effect on serum levels of prednisolone.

1 Specific radioimmunoassays have been developed for the measurement of prednisolone and prednisone in serum. 2 Serum prednisolone levels have been measured following the administration of prednisone both with and without antacids. 3 There were no significant differences in the values of Cmax (mean +/- s.d.) (251 +/- 80 ng/ml with, 245 +/- 69 ng/ml without antacid), AUC (1430 +/- 469 ng ml-1 h-1 with, 1406 +/- 530 ng ml-1 h-1 without antacid) or Tmax (1.6 +/- 0.6 h with, 1.6 +/- 0.8 h without antacid). 4 Serum prednisone levels were less than 20% of prednisolone levels at all time intervals in the subjects studied. 5 Concurrent antacid administration has no significant effect on serum prednisolone levels attained.

Antacids↗
PubMed1979

The kinetics of serum and tissue ferritins: relation to carbohydrate content.

Significant differences were observed in the rate of disappearance from plasma of ferritins purified from rat serum and from different organs. Ferritin from all sources including purified serum ferritin was rapidly removed from plasma by the liver. No difference in biological half-life was observed between apoferritin prepared by ultracentrifugation of liver ferritin and whole liver ferritin and iron-loaded animals cleared injected serum ferritin from plasma at a comparable rate to normal rats. When amounts of 100 microgram of ferritin were injected into rats the half-life was significantly lengthened. The study confirmed the fact that ferritin iron and ferritin protein were removed from plasma at the same rate. No consistent effect of acidic or more basic isoferritin composition on biological half-life was apparent. After chromatography on concanavalin A-Sepharose 6B those ferritins which were predominantly bound to Con A-Sepharose had a half-life which was approximately twice that of ferritins which did not bind. It is concluded that the variation in plasma disappearance of ferritins of different tissue origin was explainable on the basis of carbohydrate content of the molecule.

Animals↗
PubMed1979

Liver disease associated with chronic arsenic ingestion.

The association of chronic liver disease with long-standing arsenic ingestion is well documented, although the spectrum and incidence of liver disease due to arsenic remain uncertain. We report two patients with chronic liver disease and arsenical skin changes that followed previous chronic arsenic ingestion. One patient developed macronodular cirrhosis and the other non-cirrhotic portal hypertension with perisinusoidal fibrosis. The latter patient developed a primary liver cell cancer. There is only one previously reported case of malignant hepatoma in a non-cirrhotic liver complicating chronic arsenicism. Lack of awareness of this uncommon but well described cause of chronic liver disease may account for a small proportion of patients with "cryptogenic" liver disease. Previous arsenic administration should be considered as a cause of chronic liver disease, especially when typical skin changes or internal neoplasia develop.

Arsenic↗
PubMed1978

Relationship between serum ferritin and total body iron stores in idiopathic haemochromatosis.

The relationship between the serum ferritin concentration and total body iron stores was investigated in 41 patients with idiopathic haemochromatosis and 199 first or second degree relatives. Thirty-two relatives (16.1%) had increased iron stores and serum ferritin levels were increased in all but one of them. The false-positive rate in the relatives with normal iron stores was 1.8% compared with 10% for the serum iron concentration and 33% for the transferrin saturation. There was a significant correlation between the serum ferritin concentration and both the chelatable body iron and the hepatic iron concentration. We conclude that in the natural history of classical idiopathic haemochromatosis the serum ferritin concentration is usually raised when hepatic iron stores are increased and before there is architectural damage to the liver.

Adolescent↗
PubMed1978

Duodenal ferritin content and structure: relationship with body iron stores in man.

The relationship between serum ferritin and duodenal ferritin was examined in normal subjects and in patients with iron deficiency, secondary iron overload, or idiopathic hemochromatosis (IHC). A positive correlation between serum ferritin and duodenal ferritin concentrations was found in all groups. In the iron-overload conditions, duodenal ferritin concentration was lower at all levels of serum ferritin in comparison with normal and iron-deficient subjects. Patients with secondary iron overload did not differ from those with IHC, which indicates that any decrease in duodenal ferritin concentration was secondary to the excess body iron stores. Purified duodenal ferritin from normal subjects and patients with iron-overload conditions showed the same two distinct isoferritins by isoelectric focusing. After the oral administration of iron, two additional isoferritins were detected. These resembled the major isoferritins of liver.

Administration, Oral↗
PubMed1978

Drug metabolism in liver disease. Identification of patients with impaired hepatic drug metabolism.

Antipyrine half-life (AP t1/2) was measured in 62 patients with, and 10 control patients without, liver disease to ascertain possible factors which may be useful in identifying patients with abnormal drug metabolism. Antipyrine metabolism was normal or marginally impaired in patients with compensated cirrhosis or acute hepatitis, whereas it was frequently abnormal in those with chronic active hepatitis or advanced alcoholic liver disease. A high degree of correlation was found among AP t1/2 and prothrombin time, hepatic encephalopathy, and ascites. Of patients with severely impaired drug metabolism, 80% had one or more of these features. The severity of histological changes in liver biopsies was of additional help in predicting impaired drug metabolism. Concurrent drug ingestion enhanced antipyrine metabolism in most patients with liver disease as well as in control patients. Inadequate diet was associated with prolongation of AP t1/2, but other environmental factors such as alcohol ingestion, cigarette smoking, and coffee consumption did not affect rates of drug metabolism in patients with liver disease. Consideration of all of the above factors allows qualitative predictions of the rate of hepatic drug metabolism in patients with liver disease, as assessed by the AP t1/2.

Acute Disease↗
PubMed1978

Primary sarcoma of the liver. Report of a case with excellent response to hepatic artery ligation and infusion chemotherapy.

A case of primary undifferentiated sarcoma of the liver in a 66-year-old woman is reported. The similarity of the presenting symptoms to those of a hepatic abscess is emphasized. The patient's response to palliative treatment by means of hepatic artery ligation and chemotherapy was excellent. We believe that this is the first report of such a response in a sarcoma localized to the liver. This therapy may well be useful in symptomatic patients in whom partial hepatectomy is not feasible.

Aged↗