Search PubMed⌕ Search

Biomedical subjects

M S Tanner

Publications and source records attributed to M S Tanner.

At least 73 records · Page 4Linked to original sources
PubMed1989

The effect of carbon tetrachloride on the copper-laden rat liver.

Copper is believed to be hepatotoxic in Indian Childhood Cirrhosis and Wilson's disease. However, copper-loading causes only minimal hepatic damage in animal models. The hypothesis was therefore proposed that a second hepatic insult may precipitate or perpetuate liver injury in a copper-laden liver. In non-copper-dosed rats CCl4 (10 mmol/kg, i.p.) produced elevated serum AST (809 +/- 298 IU/l, normal 20 +/- 5) and ALT (295 +/- 157 IU/l, normal 6 +/- 1) and extensive liver cell necrosis, portal tract inflammation, fat deposition, and perilobular hepatocyte ballooning. In rats whose liver copper was elevated from 75 +/- 13 to 461 +/- 13 micrograms/g by oral copper supplementation, CCl4 produced much smaller increases in AST (492 +/- 80 IU/l) and ALT (172 +/- 57 IU/l) and mild focal liver cell necrosis. Fat deposition and perilobular vacuolation were not reduced. Prior copper-loading of rats unequivocally protected against the CCl4-induced liver injury. Triglyceride accumulation, however, was apparently unaffected. The possible interactions of copper with prostaglandin-mediated inflammation and with free-radical-induced liver damage are discussed.

Animals↗
PubMed1988

Copper distribution among serum proteins in paediatric liver disorders and malignancies.

Fractionation of normal serum on Sephadex G-150, followed by determination of copper, caeruloplasmin and albumin concentrations, indicated that only approximately 71% of total serum copper was associated with caeruloplasmin; less than previously reported values. Seven per cent was associated with a high molecular weight protein, designated 'transcuprein', 19% with albumin and 2% with amino acids. Compared with adult serum the concentrations of caeruloplasmin and of copper associated with caeruloplasmin were low both in serum from neonates and in serum from patients with symptomatic Wilson's disease. However, in contrast to the neonate, Wilson's disease patients exhibited a raised total serum copper and raised non-caeruloplasmin-copper. In Indian Childhood Cirrhosis serum caeruloplasmin and caeruloplasmin-copper levels were normal, whilst the non-caeruloplasmin-copper was raised. Elevated non-caeruloplasmin-copper in Wilson's disease and Indian Childhood Cirrhosis may therefore represent an overspill into the serum from a copper-laden liver. Children with malignancy showed increased serum concentrations of copper and caeruloplasmin. Both caeruloplasmin-bound and non-caeruloplasmin-bound copper concentrations were elevated. It remains to be determined whether increased 'transcuprein'- and albumin-bound copper result from a sequestering of copper released from peripherally utilized caeruloplasmin, or are associated with increased rates of caeruloplasmin synthesis.

Adolescent↗
PubMed1988

Copper in urine and hair in Indian childhood cirrhosis.

In advanced Indian childhood cirrhosis (ICC) urine copper concentration was higher (range 416-103,448 mg/g creatinine) than in other hepatic diseases (range 67-10,303 mg/g creatinine). In early ICC urine copper concentration was more modestly raised (1188-9470 mg/g creatinine), but rose to high values (2222-42,819 mg/g creatinine) after a single dose of penicillamine 20 mg/kg. A post-penicillamine urinary copper:creatinine ratio greater than 10,000 mg/g supports a diagnosis of ICC. The concentration of copper in the hair, while increased in advanced ICC, is of no diagnostic value in early cases.

Child, Preschool↗
PubMed1987

Copper protects against galactosamine-induced hepatitis.

Although copper is believed to be hepatotoxic in Wilson's disease and Indian Childhood Cirrhosis (ICC), the rat shows only minimal hepatic damage on copper-loading. To investigate the possibility that copper deposition may potentiate the effects of a superimposed hepatitis, D-galactosamine (GalN) was given to copper-loaded and control rats. In the non-copper-dosed rats, GalN 0.85 g/kg i.p. produced elevated serum AST (3731 +/- 545 IU/l; normal 64.8 +/- 2.1), ALT (2090 +/- 190 IU/l; normal 18.0 +/- 0.7), and OCT (16.7 +/- 2.6 mmol/min/ml; normal 0.12 +/- 0), and liver cell necrosis with portal infiltration. In rats whose liver copper was elevated to 1298 +/- 169 micrograms/g (control 18.7 +/- 1.7) by oral copper supplementation, GalN produced much smaller increases in AST (825 +/- 122 IU/l), ALT (103 +/- 15 IU/l) and OCT (0.27 +/- 0.02 mmol/min/ml) and minimal histological damage. Viable bacterial cell counts from faecal homogenates showed that the anaerobically cultured bacteria were reduced on copper-dosing of rats. Therefore the protective effect of copper may be due to a decrease in gut-derived endotoxin acting on the liver, or to an impaired prostaglandin synthesis or perhaps to synthesis of acute phase reactants.

Alanine Transaminase↗
PubMed1987

Hypothesis: plant and fungal biocides, copper and Indian childhood liver disease.

Hepatic copper accumulation is characteristic of Indian childhood cirrhosis (ICC) but in experimental animals causes only modest liver damage. Plant and fungal biocidal agents may be hepatotoxic, may increase hepatic copper concentration, and may be secreted in milk of lactating animals. Crotalaria species, Parthenium hysterophorus and Aspergillus flavus are possible contaminants of animal feeds in rural India, and we hypothesise that their products may be synergistic with copper in causing ICC.

Animals↗
PubMed1987

Clinical trials of penicillamine in Indian childhood cirrhosis.

The outcome in 15 children with advanced Indian childhood cirrhosis (ICC) treated with penicillamine 20 mg/kg/day was not significantly different from that in untreated children. Among children admitted to a further double blind trial who had ICC but who had not yet developed jaundice or ascites 10 treated with penicillamine and 10 treated with penicillamine plus prednisolone had a significantly improved survival. Fourteen of 29 treated cases made a clinical recovery and were alive 489 to 1460 days from the start of treatment. Biopsy specimens in survivors showed a return to normal liver histology in three, residual fibrosis in six, and inactive micronodular cirrhosis in five. Thus penicillamine, while not shown to be beneficial in advanced ICC, lowered mortality from 93% to 52% in preicteric cases of ICC.

Clinical Trials as Topic↗
PubMed1986

Optic nerve hypoplasia in infancy.

Certain features of optic nerve hypoplasia (ONH), its systemic associations and investigation are exclusive to infancy. These include the facility to use cranial ultrasound, difficulties in assessing ocular features and visual function, and neonatal hypoglycaemia and jaundice. Six infants with ONH are presented; cerebral abnormalities were demonstrated by cranial ultrasound in five. Neonatal cholestatic jaundice and hypoglycaemia occurred in one infant. Two died and represent a group likely to remain undetected unless routine ophthalmic examination of neurologically abnormal neonates is undertaken. In infancy, both ocular and systemic aspects of ONH can be investigated simply and without sedation.

Female↗
PubMed1985

Eosinophilic gastroenteritis.

We report two children with eosinophilic gastroenteritis--a 14 month old atopic boy with persistent vomiting and aspiration pneumonitis illustrates the mucosal variety of the disorder, and a 9 year old boy with eosinophilic ascites typifies serosal involvement.

Child↗
PubMed1985

A case of hepatocellular carcinoma complicating hepatitis B infection in a nine-year-old boy.

A 9-year-old boy born of Chinese parents in England, and adopted by English parents at an early age, presented with primary hepatocellular carcinoma in a non-cirrhotic liver. His serum contained hepatitis B surface antigen and 'e' antibody, a probable result of perinatal infection from an HBsAg carrier mother. The management of infants at risk of perinatal hepatitis B virus transmission should now include active and passive immunisation.

Carcinoma, Hepatocellular↗