One hundred and thirty deaths definitely or potentially due to asthma occurring in hospitals in the North East Thames region over one year were identified from death certificates and Hospital Activity Analysis records. Thirty five of these deaths were considered after independent assessment to have been directly due to asthma. Control patients who left hospital alive after acute asthma attacks were selected and matched with cases for sex, age, and hospital. Management was compared in the two groups. Inadequate monitoring, including failure to monitor arterial blood gas values, and inadequate use of nebulised 1 agonists occurred significantly more often in fatal cases. Use of sedation, inadequate treatment with steroids, exposure to potentially toxic doses of aminophylline, and inadequate clinical assessment were more common in cases than controls, but not significantly so. Failure to institute artificial ventilation contributed to seven deaths. Assessors considered important defects in management to have occurred in 83% (29/35) of the cases and 40% (14/35) of the controls. Nevertheless, most of the hospital deaths (19/35) were considered not to have been preventable. Eight other deaths in the region were attributed to the complications ofasthma or its treatment. Three ofthese were associated with gastrointestinal bleeding and one with perforation of a duodenal ulcer.Before considering policies aimed at speeding admission to hospital of patients with acute attacks of asthma it is crucial that the general standard of hospital care offered to all patients with asthma should be improved.
The metabolism and synthesis of cysteinyl leukotrienes by the isolated perfused pig kidney has been investigated. Kidneys were maintained for up to six hours in a recirculating perfusion system by using an oxygenated Krebs-Henseleit buffer containing albumin and the perfluorinated oxygen carrier, FC-43. Perfusion pressure was maintained at 12-13.5 kPa, with perfusion flow rates of 150-250 ml/min resulting in a urine output of between 20-180 ml/hr. Infusion of 3H-LTC4 into the renal artery resulted in rapid and complete metabolism, with the major urinary metabolites comprising LTE4, omega-hydroxy-LTE4, omega-carboxy-LTE4 and N-acetyl-omega-hydroxy-LTE4. The capacity of the isolated kidney to synthesize cysteinyl leukotrienes was monitored by measuring urinary LTE4 excretion; there was a basal urinary excretion of LTE4 (median 43 pg/min, range 8-470 pg/min). Neither lipopolysaccharide or human recombinant tumor necrosis factor alpha had any effect on basal excretion. Treatment with the calcium ionophore A23187, however, resulted in a 38.1 +/- 9.6-fold increase in urinary LTE4 excretion. We conclude that the isolated pig kidney, in the absence of circulating cells, can synthesize cysteinyl leukotrienes in the absence of circulating cells, which can then undergo extensive oxidative metabolism.
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