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Biomedical subjects

S J Saunders

Publications and source records attributed to S J Saunders.

At least 19 recordsLinked to original sources

Amino acid imbalance following portal diversion in the rat. The relevance of nutrition and of hepatic function.

End-to-end portacaval transposition has previously been shown to produce less hepatocellular dysfunction than end-to-side portacaval shunt in the rat. Liver weight is also significantly reduced after portacaval shunt compared to portacaval transposition and these differences are not abolished by pair-feeding. Histological evidence of CNS damage is also reduced in transposed rats compared to shunted animals. This study examines the amino acid and hormone changes in these models. The characteristic amino acid changes of chronic liver disease (decreased branched-chain and elevated aromatic amino acids) are reproduced in portacaval shunt rats, but not in portacaval transposition. The differences between these groups in the branched-chain amino acids, but not those in the aromatic amino acids, are reduced by pair-feeding. Insulin and glucagon are elevated to a similar extent in both groups. These findings add further support to a role for peripheral amino acid imbalance in the pathogenesis of portal-systemic encephalopathy. Normal liver function, maintained by replacement of portal inflow with systemic blood, appears to minimize both CNS damage and amino acid changes.

Amino Acids

Hepatic sequelae of congestive cardiac failure. Evidence for a liver lesion in patients in whom cardiac function has been restored to normal.

In order to test the hypothesis that clinical and biochemical features of liver disease due to cardiac failure regress upon relief of cardiac decompensation, 38 patients with constrictive pericarditis were studied before and after pericardiectomy for periods ranging from 1 week to 25 years. All patients were judged to be free of clinical evidence of heart failure. Hepatomegaly was present in 10 of the 38 patients studied. Of the patients studied 1-25 years after operation, 96% had elevated serum levels of total and conjugated bilirubin. The percentage Bromsulphalein (BSP) retention at 45 minutes was abnormal in all 29 patients studied 1 year or more after surgery. There was no significant correlation between the level of bilirubin or the percentage BSP retained when these were compared with the pre-operative height of jugular venous pressure, degree of pulsus paradoxus, duration of symptoms or degree of hepatic congestion. Our study reveals that the liver lesion of cardiac failure persists for up to 25 years after restoration of normal cardiac function.

Adolescent

Effect of fibrinogenolytic products D and E on fibrinogen and albumin synthesis in the rat.

Previous studies are in conflict over the effect of infusing mixed fibrinogen-fibrin degradation products on fibrinogen synthesis, as determined by changes in fibrinogen concentration or by incorporation of labeled amino acids into fibrinogen. We have injected purified homologous fragments D1 and E into rats and measured their fibrinogen and albumin synthetic rates by the [14C]carbonate technique, a method that provides quantitative estimates of hepatic secretory protein synthesis. Fibrinogen fractional synthetic rates were increased 2.5 times in animals injected with fragment D1, compared with saline-injected controls. No increase were observed in fragment E-injected animals. Neither fragment produced changes in albumin synthesis. Fragment D increased plasma fibrinogen concentration, but did not raise plasma haptoglobin levels. These results suggest that fragment D is a regulator of fibrinogen synthesis.

Albumins

Takayasu's syndrome--evidence for a liver lesion.

Liver function tests were carried out in 40 patients with Takayasu's syndrome. The alkaline phosphatase level was elevated in 73% of patients, the SGOT level in 59%, and the lactic dehydrogenase level in 84,6%. In contrast, creatinine phosphokinase levels were elevated in only 23.5% and bilirubin levels were normal in all patients. Histological abnormalities were present in 3 out of 5 patients in whom a biopsy had been performed. These abnormalities may shed light on the aetiology of this syndrome.

Adolescent

Some thoughts on medical education.

Controversial aspects of medical education are discussed, with particular reference to the medical faculty at the University of Cape Town. The drawbacks of the traditional method of selection of medical students in South Africa are outlined and present attempts to modify these in the University of Cape Town are mentioned. Curricular changes, including the liberalization of the cirriculum, are described, and finally problems in postgraduate training are enumerated.

Clinical Competence

Albumin metabolism in health and disease.

Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed.

Animals

Patterns of hepatic injury induced by methyldopa.

Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.

Adult

The effect of intragastric feeding with amino acids on liver regeneration after partial hepatectomy in the rat.

The incorporation of 14C-thymidine into DNA was measured at 4-hr intervals from 16 to 32 hr after partial hepatectomy in groups of rats. Rats forcefed solutions of amino acids or branched-chain amino acids showed a significant reduction in the DNA specific activity 24 hr after partial hepatectomy when compared to rats forced fed an equal volume of water. Intragastric feeding with ketoanalogues of the branched-chain amino acids did not alter thymidine incorporation into DNA significantly. The finding that intragastric feeding depresses DNA synthesis after partial hepatectomy contrasts with our studies indicating increased synthesis of albumin in partially hepatectorized animals receiving similar feeding and indicates different control mechanisms for DNA and albumin synthesis.

Amino Acids