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Biomedical subjects

L W Powell

Publications and source records attributed to L W Powell.

At least 217 records · Page 12Linked to original sources
PubMed1977

Serum-ferritin in diagnosis of haemochromatosis. A study of 43 families.

242 members of 43 families with idiopathic haemochromatosis were investigated for increased body-iron stores in order to assess the value of serum-ferritin determination as a screening-test to detect preclinical disease. The serum-iron concentration was elevated in only 76% of relatives with increased iron stores, and it was also elevated in 10% of relatives with normal iron stores. The percentage saturation of transferrin was elevated in all relatives with increased iron stores but also in 33% of relatives with normal iron stores. Serum-ferritin was raised in 98% of relatives with increased iron stores and in only 3 (1.8%) of those with normal iron stores. These 3 subjects consumed alcohol in excess of 100 g ethanol per day, and their serum-ferritin levels fluctuated widely. Increased iron stores were reflected in increased serum-ferritin concentrations in subjects as young as 14 years in whom the liver-iron concentration was twice the normal upper limit and before there was any evidence of architectural damage to the liver. The serum-ferritin concentration is a useful non-invasive screening test for precirrhotic haemochromatosis.

Adolescent↗
PubMed1977

Cholestatic liver disease associated with diphenylhydantoin therapy. Possible pathogenic importance of altered bile salt metabolism.

A ten-year-old boy persented with a prolonged cholestatic liver disease 5 weeks after starting diphenylhydantoin therapy. The initial phase of his illness was characterized by hepatocellular damage with swollen liver cells and centrilobular cholestasis. Severe hyperlipoproteinemia with eruptive xanthomata developed within 3 weeks of his initial jaundice. The second phase of his illness was characterized by portal tract inflammation with bile ductular proliferation and chronic cholestasis gradually resolving over a period of 15 months. It is postulated that diphenylhydantoin sensitivity produced swollen hepatocytes with hypertrophy of the smooth endoplasmic reticulum, reducing hepatic sinusoidal blood flow and the clearance of secondary bile salts. A fall in clearance of lipoproteins, including the cholesterol precursor of primary bile acid synthesis, may have been responsible for a reduction in serum bile acid concentration. High levels of serum lithocholic acid, largely unsulfated presumably due to decreased hepatic uptake, may have produced the prolonged second phase of this illness when histological changes resembled that seen in experimental animals following lithocholic acid administration.

Bile Acids and Salts↗
PubMed1977

Abnormal liver function in chronic hypervitaminosis A.

A case of chronic hypervitaminosis A is reported in a 57-year-old woman who took vitamin preparations for alopecia. Liver biopsy of the patient showed both an increase in the number and size of fat-storing cells on light microscopy and rapidly fading green autofluorescence of vitamin A. Electron microscopy confirmed the presence of engorged fat-storing cells in the space of Disse and minor toxic changes in hepatocytes. This case illustrates the early hepatic changes of chronic hypervitaminosis A and indicates a need for restriction of sales of vitamin preparations.

Biopsy, Needle↗
PubMed1977

Serum ferritin in haemochromatosis: changes in the isoferritin composition during venesection therapy.

The isoferritin composition of serum ferritin in 13 patients with untreated idiopathic haemochromatosis (IHC) has been shown to differ from normal in exhibiting an increase in isoferritins in the pH range 5.54-5.62. A similar change was observed in four patients with gross iron overload secondary to haemolytic anaemia. During the course of venesection therapy there was a progressive rise in isoferritins of pI 5.02-5.06 relative to the more basic isoferritins. These observations are consistent with previous studies showing alterations in tissue isoferritins in untreated IHC before and after venesection therapy and they are compatible with the hypothesis that the more basic isoferritins correspond to a 'storage' ferritin and the more acidic to a 'secretory' ferritin. The studies also provide further evidence for a possible biological role of the individual isoferritins.

Adult↗
PubMed1977

Immunological abnormalities associated with liver disease: cause or effect?

Immunological abnormalities are demonstrable in patients with various types of liver damage. These may be (a) non-specific and unrelated to pathogenesis, e.g. auto-antibodies such as anti-nuclear factor; (b) specifically directed against liver antigens but not pathogenetic, e.g. cell mediated immune (CMI) reactions to liver antigen as seen in experimental carbon tetrachloride poisoning; (c) of such a nature as to modify the pathology produced by hepatotoxic agents, e.g. hepatitis B virus or alcohol; (d) primarily responsible for hepatic pathology, e.g. in idiopathic chronic active hepatitis. The latter two possibilities remain unproven although there is growing evidence that immune responses do play some role in the pathogenesis of acute and chronic hepatitis B and possibly also in the pathogenesis of alcoholic liver disease. It seems much less likely that primary abnormalities of the immune systems are responsible for any type of liver disease. In summary, therefore, the available evidence suggests that immune reactions could develop as a consequence of liver damage and only in certain circumstances do these reactions play a role in the development and continuation of hepatic pathology.

Animals↗
PubMed1977

Erythromycin jaundice: diagnosis by an in vitro challenge test.

A 53-year-old housewife who had developed severe cholestatic hepatitis following the administration of erythromycin estolate therapy two-and-a-half years previously, was studied by an in vitro "challenge" test in which peripheral venous lymphocytes were cultured in the presence of erythromycin estolate, erythromycin stearate and erythromycin base. Evidence of blastogenesis was observed in response to erythromycin estolate, but not to erythromycin stearate of erythromycin base. This test thus provided evidence that the patient was "sensitized" to erythromycin estolate without exposing her to the risk of in vivo challenge. Furthermore, in contrast to previous studies, the findings provide evidence that erythromycin estolate jaundice is mediated by immunological mechanisms.

Drug Hypersensitivity↗
PubMed1976

Enhanced drug metabolism in cigarette smokers.

The effect of cigarette smoking on salivary antipyrine disappearance rate, and as an index of hepatic drug metabolism, was studied in 42 healthy subjects. Antipyrine half life was significantly shorter in smokers compared with non-smokers. To determine whether this difference was due solely to tobacco consumption eight subjects were restudied two months after they stopped smoking. The mean antipyrine disappearance rate in this group increased by 23% in contrast to that of a control group, which did not alter. Cigarette smoking contributes to the considerable variation in interindividual rates of drug metabolism.

Adolescent↗
PubMed1976

Immunological detection of isoferritins in normal human serum and tissue.

A method is described which permits the detection of isoferritins in normal human serum and tissues. The technique makes use of 125I-labelled monospecific anti-human-liver-ferritin antibody to demonstrate the isoferritins after isoelectric focussing of the purified ferritin in polyacrylamide gels. The organ-specific variation in tissue isoferritin profile previously reported in normal subjects has been confirmed by this technique using only 50 ng of each ferritin sample. Serum ferritin from normal healthy subjects was also shown to exhibit a microheterogeneity on isoelectric focussing; six clearly defined isoferritin peaks were detected in the pH range of 5.04 to 5.62. This isoferritin profile of normal serum contained isoferritins over the whole range of the various tissue isoferritins suggesting that a number of organs may contribute to the normal serum ferritin pool.

Chemical Phenomena↗
PubMed1976

Normal serum ferritin concentrations in precirrhotic hemochromatosis.

We investigated 33 of 58 members of two families with latent or precirrhotic hemochromatosis to determine its pattern of inheritance and to evaluate the serum ferritin levels as an index of iron stores. In both families, the pattern of inheritance was as an autosomal dominant trait with incomplete expressivity. Mean serum ferritin values in the affected family members were 88.5 ng per milliliter (range, 28.0 to 201.9) for males and 65.2 ng per milliter (range 23.7 to 97.0) for females, which were no different from controls (P is less than 0.5). Furthermore, the serum ferritin values did not correlate with or reflect mobilizable iron stores, and there were no relations between the serum iron, iron-binding capacity and transferrin saturation (P is less than 0.2). Thus, serum ferritin concentrations in precirrhotic familial hemochromatosis appear to underestimate iron stores. Serum ferritin levels do not help to identify such patients with increased iron stores for therapeutic phlebotomy.

Adult↗
PubMed1976

Iron absorption in the rat: the search for possible intestinal mucosal carriers.

The biological relevance of four iron-containing fractions previously detected in rat intestinal mucosal cells has been studied. The distribution of iron in these fractions obtained by chromatography on Sepharose 6B has been examined after in vivo and in vitro incubation of mucosal cells with 59Ce. In addition, the effects of phenobarbitone, cycloheximide, iron-deficiency and iron-loading on the uptake and distrubution of iron within the four mucosal cell fractions was studied. The iron in fraction I was mostly bound to intracellular membrane particles. Fraction II was shown to be ferritin. Fraction III contained some transferrin and also a protein of molecular weight similar to transferrin but which was not precipitable by antitransferrin antiserum. Quantited with the results of 'chaser' experiments suggested that, in addition to ferritin, at least two of the fractions (I and III) were involved in the process of iron absorption by the mucosal cell.

Animals↗
PubMed1976

Chronic granulomatous hepatitis.

Three cases are described in which a chronic relapsing febrile illness was associated with granulomas in the liver. None of the known causes of hepatic granulomas was present in these patients. In two cases there was clinical improvement after corticosteroid treatment and this was associated with resolution of the histological changes on liver biopsy. These three cases support the concept that chronic granulomatous hepatitis of unknown aetiology is a distinct entity.

Aged↗
PubMed1976

Haemolysis in liver disease: relationship to erythrocyte membrane function, serum bilirubin concentration and plasma electrolyte disturbances.

The pathogenesis of the mild to moderate haemolysis that is almost universal in patients with liver disease was investigated to determine if it was related to dysfunction of the red blood cell (RBC) membrane resulting from abnormalities in plasma electrolyte, urea or bilirubin concentrations. Thirty-nine patients with various forms of liver disease were investigated as well as six with miscellaneous diseases associated with plasma electrolyte disturbance. RBC membrane permeability was measured by the rate of 22Na influx. The results showed that the shortened RBC survival in liver disease is not related to morphological changes in the RBC or altered membrane integrity as measured by osmotic fragility, mechanical fragility, autohaemolysis, membrane ATP and membrane permeability.

Anemia, Hemolytic↗
PubMed1976

Isoferritin composition of tissues and serum in human cancers.

A highly sensitive technique for isoferritin detection using 125I-labeled monospecific anti-human liver ferritin antibody for the identification of isoferritins after the analysis of small quantities of ferritin by isoelectric focusing in polyacryl-amide gels was applied to the study of renal, pancreatic, and colonic carcinomas. In all tumors studied, the isoferritin composition differed from that of the corresponding normal tissue; major isoferritins with pl more basic than those of the normal tissues were consistently detected. Composition of purified ferritin from metastases closely resembled the isoferritin composition of the primary tumors. Examination of the serum isoferritin profiles of four patients with cancers did not reveal the presence of any tumor-specific changes in isoferritins. It is suggested that the abnormality in tissue ferritins in the three human cancers studied is the synthesis of major isoferritins in the more basic range, rather than the appearance of tumor-specific isoferritins in the more acidic range.

Colonic Neoplasms↗
PubMed1976

Hepatitis B-antigen subtypes in Australia as detected by radioimmunoassay.

The distribution of the major subtypes of hepatitis B surface antigen (HBsAg) was examined in asymptomatic white Australian blood donors and patients with liver disease to attempt ot assess the biological significance of these subtypes in this relatively homogeneous Caucasian population. Since previous studies have shown a very low prevalence of HBsAg in white Australians, a highly sensitive solid phase radioimmunoassay (RIA) was developed and used to subtype the antigen. A total of 46 samples of hepatitis B-antigen positive sera, obtained from 21 asymptomatic volunteer blood donors and 25 patients with liver disease, were tested. Sixteen of these 21 asymptomatic carriers were shown to have subtype "ad" whereas only seven of the patients with liver disease had this subtype. This difference was significant (P less than 0.005) and supports the view that subtype "ad" is associated with a carrier state and subtype "ay" with liver disease in Australia.

Acute Disease↗
PubMed1975

The measurement of sulphated and non-sulphated bile acids in serum using gas-liquid chromatography.

A method is described to assay sulphated and non-sulphated bile acids in serum using gas-liquid chromatography. Previously described techniques have been substantially modified to allow analysis of free and conjugated salts of the four major bile acids with particular care to ensure quantitative recoveries of lithocholic acid, its conjugates and sulphate esters. Losses of lithocholic acid inherent in some methods have been reduced by avoidance of column chromatography with alumina and extraction of lipid contaminants into heptane. Assay of the proportion of serum bile acids present as sulphate esters is achieved by the routine use of column chromatography to separate sulphated bile acids from non-sulphated bile acids followed by solvolysis of the sulphated bile acids before deconjugation. Careful selection of the conditions of strong alkaline hydrolysis ensures deconjugation of all bile salt conjugates including lithocholic conjugates which are not completely hydrolysed in weaker alkaline solutions. The trifluoroacetate derivatives of the methyl esters of the bile acids are chromatographed using 5-beta-cholanic acid as an internal standard with clear separation of the four major bile acids from the internal standard. In 10 fasting control subjects the mean serum total bile acid concentration was 5.3 muM (RANGE 1.1-16.4) including 0.7 mum sulphated bile acid (range 0-1.8). In 10 patients with acute viral hepatitis the total bile acid concentration was elevated in some but normal in others (mean 44.9 muM, range 2.7-80.3). The percentage of the total bile acid sulphated was not significantly different in the hepatitis patients compared to controls (controls 13%, range 0-35; hepatitis 23%, range 0-52). Lithocholic acid made up 13% of the total bile acid in controls (0-32%) and 18% in hepatitis patients (0-53%). Most of this lithocholic acid was sulphated (controls 81%, range 30-100; hepatitis 67%, range 37-100). Unconjugated bile acids were demonstrated in the serum of a few patients with acute viral hepatitis but in no control subjects.

Acute Disease↗