Unusual occupational toxins.

Occupational and environmental medicine affords encounters with many unusual toxins, ranging from exotic metals to rocket fuels. Twelve of the most unusual industrial toxins are reviewed here and their clinical manifestations and treatments explored: acetonitrile, acrylonitrile, boron hydrides, dimethylaminopropionitrile, dimethylformamide, hydrazines, methyl isocyanate, 2-nitropropane, phosphine, Stalinon, tellurium, and vanadium.

Measurement of cyclosporine concentrations in whole blood: HPLC and radioimmunoassay with a specific monoclonal antibody and 3H- or 125I-labeled ligand compared.

We compared cyclosporine concentrations in whole blood as measured by HPLC and by RIA with a monoclonal antibody specific for cyclosporine with 3H- or 125I-labeled cyclosporine ligand. The 3H-RIA kit slightly underestimated cyclosporine concentrations (greater than 600 micrograms/L) in comparison with HPLC. Over a wide range of concentrations, cyclosporine measured with the 125I-RIA kit correlated well with HPLC (slope = 0.99, n = 301, r = 0.98), observed for samples from recipients of kidney, heart, or liver allografts (respective slopes: 1.01, 0.93, and 1.00). The 125I-RIA standard curve was linear to 1000 micrograms of cyclosporine per liter. Inter- and intra-assay CVs for 125I-RIA measurements of cyclosporine were less than or equal to 7%. Evidently, the 125I-RIA kit involving a monoclonal antibody specific for cyclosporine is equivalent to the HPLC assay and can replace it for therapeutic drug monitoring of cyclosporine therapy.

Descriptive and mechanistic considerations of interleukin 1 and insulin secretion.

Insulin-dependent diabetes mellitus (IDDM) may be mediated in part by an autoimmune mechanism, as suggested by associated cytologic and serologic phenomena, e.g., insulitis, beta-cell necrosis, and the presence of both islet cell and insulin antibodies. Immunological approaches to the prediction and intervention in the progression of beta-cell destruction in this disease are under evaluation. A recent hypothesis is that cytokines, including interleukin 1 (IL-1), play causative roles in such autoimmune processes. Several studies have convincingly demonstrated that IL-1 is a potent modulator of beta-cell function and can potentiate or inhibit glucose-induced insulin secretion, depending on the concentration and length of exposure to IL-1. IL-1 alone or in concert with other cytokines is cytotoxic to beta-cells. The cellular mechanisms responsible for the potent effects of IL-1 on the beta-cell are unknown and just beginning to emerge. Although speculative at this time, this perspective delineates cellular mechanisms that are likely to represent possible primary sites for the IL-1 action on beta-cells. A mechanistic understanding of the effects of IL-1 on the beta-cell may clarify its role in modulating insulin release in vivo or yield insight into the pathogenesis of IDDM.

Shock syndrome associated with mastocytosis: pharmacologic reversal of the acute episode and therapeutic prevention of recurrent attacks.

Patients with mastocytosis at times experience spontaneous episodes of severe flushing and vasodilatory shock. Antihistamine therapy has not been found to prevent uniformly the recurrence of such attacks or reverse the hypotension during the acute episode when given intravenously. We previously found marked overproduction of prostaglandin D2 in two patients with mastocytosis. This suggested the possibility that prostaglandin D2 may be an important mediator in addition to histamine in mastocytosis. We have now generalized our initial findings and have found an increased production of prostaglandin D2 ranging from 1.5-to 32.6-fold in eight additional patients with severe episodes of flushing associated with mastocytosis. In one of those patients, the release of prostaglandin D2 was found to increase approximately 81-fold during an attack of flushing. Without exception, chronic combined therapy with antihistamines and the prostaglandin biosynthesis inhibitor, aspirin, has successfully prevented the recurrence of such severe attacks in these patients, further implicating prostaglandin D2 as an important mediator. The immediate treatment of an acute hypotensive episode, however, represents a different therapeutic situation. We recently observed a severe hypotensive episode in a hospitalized patient with mastocytosis being treated with an H1 receptor antagonist alone. The hypotension was found to be refractory to intravenous fluids, dopamine, and antihistamines, but was immediately reversed by intravenous epinephrine. The self-administration of subcutaneous epinephrine during episodes of flushing in other patients has also been found to ameliorate the flushing rapidly. The apparent unique effectiveness of epinephrine in this situation may derive from an ability of epinephrine to inhibit mast-cell mediator release as a result of beta-adrenergic receptor activation.