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Biomedical subjects

M S Tanner

Publications and source records attributed to M S Tanner.

At least 19 recordsLinked to original sources
PubMed1995

Normal metallothionein synthesis in fibroblasts obtained from children with Indian childhood cirrhosis or copper-associated childhood cirrhosis.

We previously demonstrated decreased metallothionein (MT) synthesis in cultured fibroblasts obtained from an American boy with findings typical of Indian Childhood Cirrhosis (ICC). We now report normal basal, copper-induced, and zinc-induced MT synthesis in the fibroblasts of two Indian boys and one Irish boy with typical ICC and one Indian boy with copper-associated childhood cirrhosis. This suggests that etiologies other than impaired MT production should be sought as the primary defect in these disorders.

Autoradiography↗
PubMed1995

The major histocompatibility complex influences the development of chronic liver disease in male children and young adults with cystic fibrosis.

BACKGROUND/AIMS: Chronic liver disease is a well-recognised complication of cystic fibrosis. Recent reports suggest that its development is not determined by specific mutations within the cystic fibrosis gene; however, familial clustering of portal hypertension cases and inappropriate immune responses against liver membrane antigens demonstrated in children with cystic fibrosis and chronic liver disease suggest that other genetic loci may be relevant. As the major histocompatibility complex has an important immunoregulatory role, we have investigated for associations with this complex and chronic liver disease in cystic fibrosis. METHODS: We have determined human leucocyte antigen class I (A and B) and class II (DR) phenotypes by serological tissue typing and class II (DR and DQ) and class III (complement component C4 and 21-hydroxylase) gene polymorphisms in 274 children and young adults with cystic fibrosis, of whom 82 had evidence of chronic liver disease with portal hypertension in 49, and 146 healthy controls. RESULTS: A marked difference in human leucocyte antigen frequency was limited to DQ6, which was found in 66.7% of cystic fibrosis patients with liver disease compared to 32.9% of patients with no liver disease (Pc < 0.03) and 28.8% of controls (Pc < 0.006). An increased frequency of the two antigens in strong linkage disequilibrium with DQ6 was also observed within this patient group, namely DR15 and B7. When the patients were stratified for the presence of portal hypertension, these observations were confirmed, but the human leucocyte antigen associations were significant only for male patients and there was no association with the age of onset of liver disease. CONCLUSIONS: These data suggest that the haplotype B7-DR15-DQ6 may carry an increased risk of development of liver disease in male cystic fibrosis patients.

Adolescent↗
PubMed1995

Reversal of Indian childhood cirrhosis by D-penicillamine therapy.

Serial liver biopsy changes have been reviewed in 30 patients with Indian childhood cirrhosis (ICC) who were randomly allocated to receive treatment with penicillamine in a dose of 20 mg/kg/day, 10 of whom also received prednisolone, and five receiving placebo. The latter died within 185 (mean, 149) days of starting treatment. Nine receiving penicillamine died within 540 (mean, 338) days, but the remainder are well 5.1-9.3 years after commencing treatment. Initial biopsies showed severe hepatocellular injury, pericellular fibrosis, inflammatory infiltration, and orcein-staining granules. Second biopsies taken within 6 months of starting penicillamine usually showed persistence of inflammation and an increase in nodularity with thick and thin active septae. Subsequently the appearances were of an inactive micronodular cirrhosis, with reduction in septal inflammatory infiltrate, hepatocellular injury, and intensity of orcein staining. This further improved to a stage of incomplete fibrous septae. The last liver biopsies at 6-60 months (in 21 survivors) showed almost normal histology in four, incomplete fibrous septae in five, and inactive micronodular cirrhosis with thin septae in 12. Mean liver copper concentrations decreased from 1,407 (SEM, 121) micrograms/g at presentation to 925 (183), 317 (100), and 127 (35) at 6, 6-18, and > 18 months after starting treatment. By contrast, a second biopsy taken in the 6 months after diagnosis in placebo-treated children showed persistence of ICC with increase in inflammation, fibrosis, and orcein staining.

Biopsy↗
PubMed1994

Copper associated childhood cirrhosis.

Several papers have reported severe liver disease in association with massive hepatic copper accumulation, which do not seem to be either of the recognised copper associated liver diseases, namely Wilson's disease and Indian childhood cirrhosis. A further case is reported in which novel copper kinetic studies were carried out using the stable isotope 65Cu, showing that this patient did not suffer from Wilson's disease. It is suggested that these cases can be divided into two groups on the basis of age, clinical course, and history of excessive copper ingestion. The benefits of using 65Cu for in vivo studies of copper metabolism is discussed.

Bangladesh↗
PubMed1994

Development of a PCR probe test for identifying Pseudomonas aeruginosa and Pseudomonas (Burkholderia) cepacia.

AIMS: To develop a system of species specific polymerase chain reaction (PCR) and DNA hybridisation based on 16s ribosomal RNA sequences for the identification of Pseudomonas aeruginosa and Pseudomonas (Burkholderia) cepacia in sputum from children with cystic fibrosis. METHODS: Most of the 16s rRNA sequences from strains of Ps aeruginosa, Ps (Burkholderia) cepacia, and Ps putida were determined. PCR primers and DNA probes were synthesised from suitable sequences and then evaluated on bacterial cultures and sputum samples. RESULTS: About 1000 bases of sequence was obtained from strains of Ps aeruginosa, Ps (Burkholderia) cepacia, and Ps putida. PCR of bacterial cultures was species specific, but PCR on sputum resulted in some non-specific amplification products. The subsequent hybridisation reaction was species specific. CONCLUSION: A species specific system of PCR and DNA hybridisation based on 16s rRNA sequences is applicable in clinical practice, and may aid the early diagnosis of respiratory tract infection with small numbers of Ps aeruginosa and Ps (Burkholderia) cepacia in patients with cystic fibrosis.

Base Sequence↗
PubMed1994

Liver histology in the arthrogryposis multiplex congenita, renal dysfunction, and cholestasis (ARC) syndrome: report of three new cases and review.

We report three cases from two unrelated families of infants with arthrogryposis multiplex congenita, cholestatic jaundice, and renal Fanconi's syndrome. In both families the parents were consanguineous. All three children died by 7 months of age. This association was first reported in 1973 by Lutz-Richner and Landolt and again in another family by Nezelof et al in 1979. However, because of differing liver histology the two sibships were considered to have two separate conditions. Based on the histological findings in one of our cases we propose that all cases described so far represent variation within a single syndrome.

Abnormalities, Multiple↗
PubMed1993

Pneumococcal infection in the newborn.

Two fatal cases of invasive pneumococcal disease in the newborn are reported, both acquired from the maternal vagina. The rarity of vaginal carriage of pneumococcus suggests that this organism has a higher invasion to colonisation ratio than group B streptococcus and maternal carriage or neonatal colonisation should be more aggressively treated.

Adult↗
PubMed1992

Genotype analysis for delta F508, G551D and R553X mutations in children and young adults with cystic fibrosis with and without chronic liver disease.

Genetic factors have been implicated in the pathogenesis of liver disease in cystic fibrosis. To investigate whether liver disease is associated with particular mutations of the defective gene in cystic fibrosis, we have determined the frequencies of three mutations--delta F508, G551D and R553X--in 111 children and young adults with cystic fibrosis by analysis of genomic DNA segments amplified by the polymerase chain reaction. Twenty-nine patients had severe liver disease with portal hypertension, 19 had clinical and/or biochemical evidence of liver disease but no associated portal hypertension and 63 had no evidence of liver disease. No significant differences in the frequencies of the delta F508, G551D or R553X mutations in the three clinical subgroups were found, and we conclude that the development of liver disease in cystic fibrosis is unlikely to be associated with a specific mutation in the gene. However, because 27% of cystic fibrosis chromosomes do not have a defined mutation, this possibility cannot be ruled out. A familial concordance for clinical liver disease of 20% in this study, compared with a reported prevalence of 4.7%, suggests that genes outside the cystic fibrosis locus and/or environmental factors are involved in the pathogenesis of liver disease in cystic fibrosis.

Adolescent↗
PubMed1992

Alpha-tocopherol deficiency fails to aggravate toxic liver injury but liver injury causes alpha-tocopherol retention.

The possible aggravation of liver injury by impaired cellular antioxidant function was investigated. A vitamin E-deficient diet (0.5 mg/kg alpha-tocopherol; control 100 mg/kg) significantly reduced rat liver alpha-tocopherol concentrations after 4 weeks (1.8 +/- 1.7 micrograms/g; control 34.4 +/- 2.4 micrograms/g, p < 0.001). The effects of copper loading (Cu, 3 g/kg diet); galactosamine (GalN, 0.85 g/kg i.p.); or carbon tetrachloride (CCl4, 10 mmol/kg i.p.) were examined. Serum aspartate transaminase activity was elevated slightly by vitamin E deficiency but not by hepatic copper accumulation. In vitamin E-replete (E+) and vitamin E-deficient (E-) rats, GalN or CCl4 caused a large and comparable elevation in serum AST and OCT activity. This effect on AST was markedly reduced by copper loading in vitamin E replete (E+) rats, but in E(-) rats copper had significantly less protective effect. Copper also diminished the OCT response to GalN in E+, though not E-, rats. A significant rise in total hepatic alpha-tocopherol content followed administration of GalN or CCl4 in both normocupric and copper-laden E(-) rats. Thus alpha-tocopherol deficiency (a) was not hepatotoxic per se; (b) failed to potentiate the toxicity of copper, GalN or CCL4; but (c) partially abolished the protection by copper against toxin-induced liver injury. Retention of hepatic alpha-tocopherol after liver damage may partly explain low serum vitamin E levels seen in clinical liver disease.

Animals↗
PubMed1992

The prevention of Indian childhood cirrhosis.

Previous studies have led to the hypothesis that the gross hepatic copper storage characteristic of Indian childhood cirrhosis (ICC) is due to the early introduction of animal milk feeds which have been contaminated with copper from brass household utensils. Amongst the families of 100 cases of ICC, the incidence of ICC in children born after dietary advice had been given (1/86) was significantly lower than in older siblings (12/125). This study attempted to document the incidence of ICC and the usage of brass before and after an intervention programme in Pune District advising against this pattern of infant feeding. The study encountered numerous difficulties in data gathering, but documented a fall in ICC prevalence resulting in its virtual disappearance in Pune District. This contrasted with an unchanged incidence in Chandigarh. Although a fall in brass usage was seen in Pune District, this was actually a spontaneous sociological change rather than a result of health education.

Alloys↗
PubMed1992

Liver and biliary problems in cystic fibrosis.

There have been striking advances in the management of complications of cirrhosis in the 50 years since biliary cirrhosis was recognised as a feature occurring in a minority of patients with cystic fibrosis. Many questions remain unanswered with regard to its pathogenesis, its effect on other systems, morbidity and mortality and to its optimum management. Factors which may initiate liver disease and/or cause progressive biliary fibrosis leading to biliary cirrhosis in some cystic fibrosis patients are being defined but much is still poorly understood and further research is required. Clinical and pathological studies confirm that cirrhosis is frequently asymptomatic and only slowly progressive, with the prevalence rising with age. In a recent large epidemiological study, however, it was found that the age related prevalence fell in patients over the age of 20 years although deaths from liver disease were rare. Does the presence of liver disease cause premature respiratory death in teenagers? Current treatments control variceal bleeding, the important sequel for most patients with biliary cirrhosis, with less morbidity and mortality than in the past but require reappraisal as newer techniques become available. Endoscopic radiologically controlled methods are emerging as an important adjunct to the surgical control of biliary complications which cause symptoms in up to 4%. Ursodeoxycholic acid improves liver function tests but its effect on hepatic fibrosis and portal hypertension will only be demonstrated by large scale prospective controlled trials. Should liver transplantation have a larger role in management? In this chapter we have attempted to summarise the current state of knowledge and to assess the efficacy of present management.

Biliary Tract Diseases↗
PubMed1992

Lafora disease: a progressive myoclonus epilepsy.

Lafora disease is a rare inborn error of metabolism resulting in storage of a polyglucosan in tissues including the brain, skin and liver. Four children are described with progressive myoclonus epilepsy and intellectual deterioration in whom this diagnosis was made. In two the diagnosis was confirmed by the presence of periodic acid schiff (PAS) positive, diastase resistant, colloidal iron staining inclusion material in the liver when they were referred to a paediatric gastroenterologist with abnormal liver function tests. In one, the diagnosis was made from cerebellar biopsy, although on retrospective review the liver biopsy performed at this time was abnormal. In a fourth child, whose sibling was affected, histological diagnosis was confirmed by skin biopsy, although clinical and EEG findings had been highly suggestive for several years. The disease has autosomal recessive inheritance, is progressive and the prognosis is poor. Paediatricians should be aware of this diagnosis, which is often delayed, as early histological diagnosis allows prognostic and genetic counselling and optimal treatment. Although the diagnosis was made by liver or brain biopsy in three cases, skin biopsy offers a reliable, less invasive means of diagnosis.

Adolescent↗
PubMed1991

Prevalence of liver disease in cystic fibrosis.

To assess the prevalence, demography, and clinical features of liver disease among patients with cystic fibrosis the case notes of 524 patients of all ages who were attending the cystic fibrosis clinic were studied. Computer databases were used to establish the condition of the liver in a further 576 such patients. The overall prevalence of overt liver disease indicated by the presence of an enlarged liver or spleen (or both) was 4.2%. The age related prevalence rose to a peak in adolescence, and then fell in patients over 20 years old. The implied increase in mortality among those with liver disease was not explained by deaths from liver disease, which were rare. Male patients were significantly more affected than female, the ratio being 3:1 among adolescents. Increasing prevalence of liver disease in patients with cystic fibrosis is, therefore, not just a result of longevity.

Adolescent↗
PubMed1991

Autoimmune chronic active hepatitis in a family.

A positive family history of autoimmune disease is common among patients with autoimmune chronic active hepatitis, but usually autoimmunity is directed at organs other than the liver. We document for the first time the multiple occurrence of autoimmune chronic active hepatitis in a family. Out of a sibship of seven, three sisters developed this, one sister developed coeliac and autoimmune thyroid disease, one sister showed serological signs of autoimmunity, while the two brothers were well with no signs of autoimmunity. HLA typing showed that in association with the female sex DR3 seems to be more important than B8 in conferring susceptibility to autoimmune chronic active hepatitis, at least in this family.

Adolescent↗