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Biomedical subjects

C Liddle

Publications and source records attributed to C Liddle.

46 records · Page 3Linked to original sources

Chronic non-A, non-B hepatitis: lack of correlation between biochemical and morphological activity, and effects of immunosuppressive therapy on disease progression.

A study was made of 52 patients considered to probably have chronic non-A, non-B hepatitis who were seen during an eight-year period at Westmead Hospital, Sydney. The patients were followed for a median of 28 months to assess the natural history of the disease and, in a small number of patients, the effect of immunosuppressive therapy on disease progression was examined. In 94% of cases, infection appeared to have been acquired by a parenteral route; the remainder were sporadic infections. Fifty-six per cent of the patients had mild constitutional symptoms and the remainder were asymptomatic. Similarly, 54% of patients had no signs of chronic liver disease and none exhibited signs of hepatic decompensation. Liver biopsies were performed in 42 patients; chronic active hepatitis with or without cirrhosis was present in 90%. However, neither the presence of symptoms nor the degree of biochemical abnormality were predictive of disease severity as determined histologically. Among eight patients treated with corticosteroids (with or without azathioprine), six underwent follow-up liver biopsy. Quantitative analysis of inflammatory and fibrotic changes indicated significant (p less than 0.01) progression of histological severity during a median 33 months (range 7-98 months) between biopsies with cirrhosis developing in four instances. In contrast, among the seven untreated patients rebiopsied after a median of 16.0 months (range 11-37 months) there was no overall change in histological severity and only one patient developed cirrhosis. it is concluded that histological assessment is required in all patients suspected of having chronic non-A, non-B hepatitis as other means of assessment are unreliable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of liver regeneration on hepatic cytochrome P450 isozymes and serum sex steroids in the male rat.

Partial hepatectomy in male adult rats results in raised serum estrogen levels and demasculinization of certain aspects of hepatic metabolism. Some constitutive forms of hepatic cytochrome P450 are sex-dependent and we have previously demonstrated demasculinization of cytochrome P450 isozyme distribution in a rat model of cirrhosis. As liver regeneration is an integral component of cirrhosis, the present study was performed to ascertain the effects of regeneration on hepatic cytochrome P450 isozyme composition and serum sex steroid concentrations. Adult male rats were subjected to 65% partial hepatectomy or sham-operation. The position-specific hydroxylation of androstenedione was used as a probe for isozyme activity. Serum sex steroids, hepatic enzymes, and hepatic deoxyribonucleic acid synthesis were measured in groups of animals at 0, 6, 24, 48, and 72 h. By 72 h total microsomal cytochrome P450 in partially hepatectomized animals had fallen to 66% of that in nonoperated animals. In both partially hepatectomized and sham-operated animals, androstenedione 7 alpha- and 16 beta-hydroxylase activity returned to preoperative levels by 48 h. However, the male-specific androstenedione 16 alpha- and 6 beta-hydroxylase activities and aromatase activity remained suppressed in partially hepatectomized liver. Serum estradiol increased eightfold in partially hepatectomized rats and peaked at 6 h followed by a gradual fall to control values. No change in serum estradiol was observed in sham-operated animals. We conclude that demasculinization of hepatic oxidative metabolism occurs in regenerating rat liver. The early rise in serum estradiol is consistent with a role for this hormone in the changes in cytochrome P450 observed, and possibly the process of liver regeneration.

Androstenedione↗

Hepatitis B in Australia: determinants of intrafamily spread.

Strategies for the control of hepatitis B virus (HBV) infection rely on information about the modes of spread and the numbers of 'at risk' individuals in particular community subgroups. This study prospectively examined 377 family and household contacts of 145 patients with HBV infection to determine the incidence of and factors determining intrafamily spread. Two hundred and forty were contacts of 68 Asian patients and 137 were contacts of 77 Caucasian patients. Serological examination of all contacts demonstrated that 161 (43%) had HBV markers including 60 (16%) who were HBsAg positive. HBV transmission within families was greater if the index case was Asian rather than Caucasian (p less than 0.001), had an HBsAg positive mother rather than an HBsAg positive father (p less than 0.01), was HBeAg positive rather than HBeAg negative (p less than 0.002), and had chronic rather than acute HBV infection (p less than 0.001). However birthplace, family size, and the activity of the liver disease of the index case did not influence HBV transmission. Within Asian families, the risk of non-sexual and non-vertical transmission of hepatitis B appeared to be as high as 18% and continued after the first three years of life. It is concluded that hepatitis B prevention programmes should include vaccination of families of chronic HBV carriers, particularly those from endemic regions such as Asia.

Adolescent↗

A new slide holder for immune staining.

The construction of a Perspex slide holder for use in immune staining is described. The apparatus allows large numbers of slides to be stained at once and makes the procedure less tedious than it would otherwise be.

Immunoenzyme Techniques↗

Institutional rearing, parenting difficulties and marital support.

A prospective follow-up study was undertaken of two groups of women first studied in the mid 1960s when they were children: 94 girls reared in institutions to which they had been admitted because of a breakdown in parenting, and 51 girls in a general population comparison group. Both groups were interviewed in detail when aged 21-27 years and home observations were undertaken for those with young children. The institution-reared women showed a markedly increased rate of poor psychosocial functioning and of severe parenting difficulties in adult life. However, the support of a non-deviant spouse and of good living conditions in adult life provided a powerful protective effect.

Adult↗

A critical investigation of the Oxford tumour marker Ca1 in the histological diagnosis of breast cancer and pre-cancer.

Ca1 antibody reacted focally with all of the 20 cancers examined, but also with 12 out of 13 fibroadenomata and with each of 20 normal breasts. These observations indicate that there are severe limitations to the use of Ca1 antibody for defining benign versus malignant processes. Ca1 is most specific in terms of the cytoplasmic staining of tumours versus normal tissues. If a hierarchy of maximal staining is drawn up, cancers and fibroadenomata appear at the top, with normal tissue found in various types of breast in the middle, and non-neoplastic lesion such as epitheliosis, hyperplasia and apocrine change at the bottom of the hierarchy. There is a growing list of non-cancerous tissues which show reactivity to Ca1. In July 1983 this list numbered about 15. The designation 'Ca' is inappropriate.

Adolescent↗

Identification of new urinary metabolites in man of quinine using methane chemical ionization gas chromatography-mass spectrometry.

1. Six new metabolites of quinine have been identified in urine of man by methane chemical ionization g.l.c.--mass spectrometry. 2. Metabolites identified were: unchanged quinine and dihydroquinine, 3-hydroxyquinine, 3-hydroxydihydroquinine, 6'-hydroxycinchonidine, 6'-hydroxydihydrocinchonidine, quinine-10,11-epoxide and quinine-10,11-dihydrodiol. 3. 10-Chloro-11-hydroxydihydroquinine was identified as an artifact of the isolation procedure. 4. Chloroquine and desethylchloroquine (artifacts) were identified in the urine, 17 days after completion of a 48 h treatment with chloroquine.

Gas Chromatography-Mass Spectrometry↗

Role of the oestrogen receptor in liver regeneration in the male rat.

Partial hepatectomy in male rats results in raised serum oestrogen levels, nuclear binding of oestrogen receptor (ER) and feminization of certain aspects of hepatic metabolism. It has been proposed that these changes may have an important role in liver regeneration. The present study was performed to ascertain the effects of the oestrogen agonist diethylstilbestrol (DES), 2 mg/kg, and the oestrogen antagonist tamoxifen (TAM), 2 mg/kg, on liver regeneration induced by partial hepatectomy in the male rat. Regenerative activity was determined by incorporation of [3H]-thymidine into hepatic DNA as well as by measurement of liver remnant weight. Following partial hepatectomy, there was a trend towards an increase in liver remnant weight at 24 h in rats treated with DES (DES, 5.95 +/- 1.52 g; vehicle, 4.87 +/- 0.66 g; P = 0.06) though by 48 h no effect was found. Tamoxifen treatment did not significantly affect liver weight at 24 h but by 48 h there was a highly significant reduction in liver remnant weight (TAM, 5.41 +/- 0.85 g; vehicle, 7.31 +/- 1.43 g; P < 0.001). Neither DES nor TAM treatment influenced liver regeneration as determined by [3H]-thymidine incorporation into hepatic DNA. We conclude that pharmacologic manipulation of oestrogens does not influence the initiation of the regenerative process but that oestrogen may facilitate later phases of hepatic growth.

Animals↗