Hematopoietic effects in mice exposed to arsine gas

Arsine gas is a potent hemolytic agent. Concern about semiconductor workers prompted an in-depth study of arsine at the National Institute of Environmental Health Sciences to determine the hematopoietic effects of prolonged exposure to this gas. Female B6C3F1 mice were exposed by inhalation to 0, 0.5, 2.5, and 5 ppm arsine, 6 hr/day for 14 days. Body weights of exposed mice were comparable to those of controls, but a marked, concentration-related splenomegaly was observed. Higher level arsine exposure produced statistically significant decreases in red blood cells, hematocrit and hemoglobin, with increases in white blood cell counts and mean corpuscular volume of red blood cells. Erythropoiesis as measured by quantitation of erythroid precursors in culture revealed a marrow reduction of colony-forming unit erythroids/femur cells for all treated groups on Day 3 postexposure and only at the 5 ppm dose group on 24 days postexposure, while splenic erythropoiesis increased at higher concentrations of arsine. There was no alteration in bone marrow cellularity and a less significant effect on granulocyte-macrophage progenitors. A 12-week study of arsine at 0, 0.025, 0.5, and 2.5 ppm (6 hr/day) by inhalation showed similar effects on hematopoiesis in mice. In conclusion, arsine exposure at low concentrations produces a stress on the hematopoietic system characterized by hemolysis, which persists for a prolonged period following exposure.     

Pharmacokinetics of two per cent rectal methohexitone in children

Plasma methohexitone concentrations were determined in 60 children, aged one to six years, following administration of 15 mg.kg-1, 20 mg.kg-1, 25 mg.kg-1 or 30 mg.kg-1 two per cent rectal methohexitone. Time to the onset of sleep was determined by a blinded observer and venous blood samples obtained 15, 30, 45 and 120 minutes following drug administration. Fifty of 60 children were asleep within 15 minutes. Nine of the ten children that did not fall asleep were sedate and could be separated easily from their parents to undergo inhalational induction of anesthesia. Time to the onset of sleep was inversely related to the dose of rectal methohexitone administered. Sleep was achieved more reliably following the use of 25 to 30 mg.kg-1 rectal methohexitone. In addition, plasma methohexitone concentrations following 30 mg.kg-1 rectal methohexitone were significantly higher for up to 120 minutes following drug administration than the plasma concentrations achieved after 15 mg.kg-1 or 20 mg.kg-1 methohexitone. There was no difference in the incidence of complications. The authors recommend that clinical circumstances be carefully considered and the dose of rectal methohexitone administered be individualized to meet the specific anaesthetic requirements of each child.     

An in-vitro study of the interactions between intravenous induction agents and the calcium antagonists verapamil and nifedipine

Thiopentone, propofol and etomidate inhibit the contractions of the rat isolated atria and portal vein. The actions of thiopentone and propofol summate with those of verapamil and nifedipine. Verapamil potentiates the action of etomidate on both preparations. The depressant actions of thiopentone and propofol on the portal vein are associated with a reduced response to calcium. Etomidate does not reduce the response to calcium in this preparation.     

Trace element status in multiple sclerosis

We compared trace element status in multiple sclerosis (MS) patients (n = 27) with and without treatment with corticosteroids and groups of healthy subjects. Concentrations of plasma ceruloplasmin, selenium, and zinc and erythrocyte (RBC) glutathione peroxidase, Se, and Zn were similar in all groups. RBC copper concentrations were significantly lower in MS patients than in control subjects (mean +/- SEM: 0.048 +/- 0.005 vs 0.060 +/- 0.002 mumol/g Hb) because of decreased RBC Cu with steroid therapy. RBC Zn-Cu ratios were significantly higher (14.9 +/- 1.0 vs 10.1 +/- 0.3) in MS patients than in control subjects, differing in both groups of MS patients. In MS and control subjects, RBC Cu correlated significantly with RBC Zn (r = 0.56, 0.49). Disease acuity and disability had no effect on trace-mineral status. These data suggest that in MS there is altered Cu and Zn homeostasis that may cause or result from the disease and is influenced by corticosteroid therapy. Systemic trace element alterations might provide clinically useful markers of MS.