Pancytopenia and aplastic anemia: a retrospective study

During January 1971--June 1975 we examined 195 patients with pancytopenia. The cause was bone marrow failure in 67.7% of cases (classic aplastic anaemia in 11.3%) hypersplenism in 7.7%, massive blood transfusions in 1.5%, severe infections in 9.7% (Gram-negative in 3%), and various other conditions in 7.8%. Records were insufficient for diagnosis in 5.6% of cases. Analysis of the 22 patients with aplastic anaemia showed no apparent aetiology in 16 (72.7%), previous phenylbutazone ingestion in 2, and Fanconi-type anaemia in 4 of 7 children. One-year survival was 73.7%, 2-year survival 71.4%, 3-year survival 63.6% and 4-year survival 57.1%. Marrow-investigation of the 21 available samples showed that 6 were acellular, 11 hypocellular and 4 normocellular. All patients received at least temporary therapy with anabolic steroids but its effectivity could not be satisfactorily assessed. Five patients died within 7 months and 5 patients went into remission, needing no further therapy. The initial haematological features of the 5 patients who died were not significantly different from those of the rest of the patients.     

Amoxycillin versus ampicillin in treatment of exacerbations of chronic bronchitis

To compare the efficacy and unwanted effects of amoxycillin and ampicillin in the treatment of acute exacerbations of chronic bronchitis, 199 patients were recruited from 28 centres into a double-blind between-patient comparison of four regimens: ampicillin 250 mg or 500 mg, amoxycillin 250 mg or 500 mg, each given orally three times daily for seven days. In these doses, amoxycillin and ampicillin were equally effective and there was no apparent advantage in using the higher dose of either drug in preference to the lower dose. Unwanted effects were few. Only in five patients did diarrhoea lead to withdrawal of therapy and there was no significant difference between the two drugs in this respect. Rashes occurred in four patients, all on ampicillin.     

On the question of an electrokinetic requirement for phospholipase C action

The phospholipase C of clostridium welchii (alpha toxin) has an absolute requirement for trace quantities of Ca2+. It attacks pure phosphatidylcholine particles (smectic mesophases) having a close-packed bilayer structure only when their surface zeta potential is made positive by the addition of certain divalent ions (e.g., Ca2+) to the aqueous phase or by the presence of low concentrations of long chain cations to the lipid. Alternatively, if the rotational freedom of individual phospholipid molecules is increased by the insertion of short n-alkanols (e.g., hexanol) into the bilayer or when a monolayer of the substrate at an air/water interface is expended, enzymic hydrolysis can occur without any requirement for a net postive charge on the surface.     

Aurothioglucose inhibits murine thioredoxin reductase activity in vivo

Gold (I)-containing compounds, including aurothioglucose (ATG), are potent in vitro inhibitors of several selenocysteine-containing enzymes. Gold compounds have also been shown to potentiate the virulence of several viruses in mice, including coxsackievirus, implicated as a possible infectious agent in Keshan disease. One possible mechanism by which gold compounds may be increasing the virulence of viral infections in mice is by acting as a selenium antagonist in vivo and inducing oxidative stress. To investigate the possible role of gold compounds in inducing oxidative stress in mice, we assessed the ability of ATG administered in vivo to inhibit the activity of the selenocysteine-containing enzymes thioredoxin reductase (TR) and glutathione peroxidase (GPX1). Doses as low as 0. 025 mg ATG/g body weight caused significant and prolonged inhibition of TR activity in all tissues examined. No such inhibition of GPX1 activity was seen, indicating differential in vivo sensitivity of the enzymes to inhibition by ATG. In liver and heart, some recovery of TR activity was observed after a 7-d period, but no recovery was observed in pancreas or kidney. Because TR is involved in several important cellular redox functions, its inhibition most likely will affect multiple cellular processes. These results indicate that in vivo administration of ATG results in significant and long-lasting inhibition of TR activity. Such inhibition of TR could lead to increased levels of oxidative stress in vivo, thereby increasing the virulence of several viruses including the coxsackievirus.