Halothane hepatitis in a South African population frequency and the influence of gender and ethnicity

No Abstract

Renal function, sodium and water homeostasis in patients with idiopathic extrahepatic portal vein thrombosis compared with normal healthy controls

Objectives. To determine whether portal hypertension in the absence of liver disease contributes to changes in renal function and renal sodium and water handling.Methods. Nine patients with extrahepatic portal vein thrombosis (PVT) with normal liver function and histology were compared with 9 matched healthy control subjects. All underwent standard measurements of glomerular filtration rate and effective renal blood flow using inulin and paraaminohippuric acid (PAH) clearances, respectively. Sodium excretion and renin and aldosterone levels were studied before, during and after an intravenous saline infusion,Results. At baseline there were no differences in inulin clearance, PAH clearance, fractional excretion of sodium and free water excretion. During and after the saline infusion both groups showed a significant increase in sodium excretion with a reduction in water excretion, while the PAH and inulin clearances remained unchanged. Although aldosterone and renin levels both fell after the infusion, aldosterone levels were significantly lower in the PVT group. There were no other significant differences between the PVT and control groups.Conclusion. Renal function and sodium and water handling were comparable in healthy controls and patients with PVT. It is unlikely that portal hypertension alone plays a significant role in the impaired ability to excrete sodium and water in patients with liver cirrhosi

Variegate porphyria in South Africa, 1688 - 1996 - new developments in an old disease

Variegate porphyria, an autosomal dominant inherited trait resulting in decreased activity of protoporphyrinogen oxidase, the penuttimate haem biosynthetic enzyme, is characterised clinically by photosensitive skin disease and a propensity to acute neurovisceral crises. The disease has an exceptionally high frequency in South Africa,owing to a founder effect. The specific mutation in the protoporphynnogen oxidase gene sequence which represents this founder gene has been identified. Genetic diagnosis is therefore now possible in families in whom the gene defect is known. However, the exact nature and degree of activity of the porphyria can only be determined by detailed quantitative biochemical analysis of excreted porphyrins. The relative contributions of the acute attack and the skin disease to the total disease burden of patients with variegate porphyria is not static, and in South Africa there have been significant changes over the past 25 years, with fewer patients presenting with acute attacks, leaving a greater proportion to present with skin disease or to remain asymptomatic with the diagnosis being made in the laboratory. The most common precipitating cause of the acute attack of VP is administration of porphyrinogenic drugs. Specific suppression of haem synthesis with intravenous haem arginate is the most useful treatment of a moderate or severe acute attack. Although cutaneous lesions are limited to the sun-exposed areas, management of the skin disease of VP remains inadequate

Fibrinogen is degraded and internalized during incubation with neutrophils, and fibrinogen products localize to electron lucent vesicles.

A biologically relevant relationship exists between neutrophils and coagulation processes. Several studies have focused on the ability of neutrophil proteases (both intracellular and membrane-associated) to degrade fibrinogen. The present study investigates the events following the interaction of activated neutrophils with soluble fibrinogen. During incubation of PMA-stimulated neutrophils with fibrinogen at 37 degrees C, fibrinogenolysis occurred, and degraded fibrinogen became associated with the neutrophil. Immunoelectron microscopy identified these fibrinogen products to be located within electron lucent vesicles, and not on the surface of the cell, suggesting that they are internalized. Although a specific interaction between fibrinogen and the neutrophil membrane might assist uptake, in the presence of physiological concentrations of fibrinogen, internalization occurred largely via a non-specific pinocytic process. Studies at low temperature revealed that both intact and degraded forms of fibrinogen can associate with neutrophils. The fibrinogen products detected intracellularly in experiments performed at 37 degrees C might represent uptake of degraded as well as intact forms of fibrinogen, the latter being rapidly degraded intracellularly. This route of fibrinogenolysis contributes minimally to the overall extent of the degradation process, the majority occurring extracellularly. Neutrophils thus possess a proteolytic mechanism for preventing accumulation of surface ligand, perhaps allowing them to evade the immunomodulatory effects of such ligands during inflammation

A novel 2,18-bridged biliverdin derivative

Base-catalysed dehydrohalogenation of a 3,18-bis(2-ohloroethyl)biliverdin 1 affords a novel 3-vinylbiliverdin 3 in which the 2- and 18-positions are bridged with a propano-tether; the structure of 3 has been established using single crystal X-ray and 1H nuclear Overhauser effect studies