The optimal serum concentration of theophylline for the management of acute airways obstruction was evaluated by comparing the response to target concentrations at the extremes of the usual therapeutic range. 174 patients requiring intravenous theophylline were randomly assigned to a target concentration of 10 or 20 mg/L. Control of theophylline dosage using measured theophylline concentrations and evaluation of efficacy and toxicity was performed under double-blind conditions. 87 patients (50%) required hospital admission. Of these, 54 patients (62%) were followed throughout their hospital admission and reviewed at an outpatient clinic approximately 1 week after discharge. The duration of hospital stay, and rate and extent of improvement in peak expiratory flow rate were not different between the groups. There was significantly more toxicity in the 20 mg/L group. The initial target concentration for theophylline in the management of acute airway obstruction should be 10 mg/L under circumstances where concentration is used to control theophylline dosages.

C3H/HeJ mice were used to study the origin and nature of endotoxin-induced glucocorticoid antagonizing factor (GAF). In conventional mice GAF is believed to be responsible for a variety of effects that occur as a result of an injection of endotoxin, including the inhibition of hormonal induction of hepatic phosphoenolpyruvate carboxykinase and of glyconeogenesis. Responses in such animals are seen whether the endotoxin is extracted with phenol-water or with trichloroacetic acid. C3H/HeJ mice do not respond (or produce GAF?) after an intravenous injection of phenol-water lipopolysaccharide, but they react normally (produce GAF?) when given a trichloroacetic acid preparation. They also behave the same as conventional animals when injected with serum from poisoned normal mice, especially when the reticuloendothelial system of the donors has been activated by prior injections of Zymosan or heat-killed tubercle bacilli. The C3H/HeJ mice have been used, therefore, as assay animals to establish that peak levels of GAF appear in donor serum about 2 h after an injection of lipopolysaccharide, and it is produced intraperitoneally in C3H/HeJ mice given a mixture of endotoxin and peritoneal exudate cells derived from responder mice. GAF elutes from Sephadex G-200 along with markers of known molecular weight in the region of 100,000 to 200,000. It is inactivated by trypsin and by heating at 75 degrees C for 1 h.

No abstract

A smokeable product called Kronic, is legally available, sold under five product names, and marketed in New Zealand as containing natural extracts. Two such products called Pineapple Express and Purple Haze were purchased from shops in Auckland city. They were investigated for the presence of synthetic drugs specifically synthesized for recreational purposes. The synthetic cannabinomimetics identified were JWH-018, JWH-073, JWH-122, JWH-250, and 1-pentyl-3-(4-methoxybenzoyl)indol. A compound not previously reported in such designer drug preparations 1-butyl-3-(4-methoxybenzoyl)indol was also seen. There was a marked variation in the content of these compounds within a named brand. The pharmaceutical benzodiazepine phenazepam (fenazepam) was identified as a constituent, along with certain cannabinominetics, in nearly all of the Kronic samples examined. Phenazepam has not previously been reported as a constituent of designer drug or herbal high products. The amount of phenazepam was approximately 1 mg per gram of Kronic leaf material. Use of these products could result in severe toxicity.

The role of pregnenolone sulphate in adrenal steroid biosynthesis and the ability of the human adrenal gland to synthesize and secrete dehydroepiandrosterone (DNA) and dehydroepiandrosterone sulphate (DHA sulphate) was investigated. The presence of pregnenolone sulphate and DHA sulphate was demonstrated by measuring their concentrations in human adrenal tissue. Pregnenolone sulphate was metabolized in vitro mainly to free steroids, including DHA and cortisol, as well as directly to DHA sulphate in some cases. Similar results were obtained upon perfusion of the adrenal gland in situ with [14C]pregnenolone and [13H]prenenolone sulphate as the substrates and isolating the metabolites from the adrenal venous blood. Dehydroepiandrosterone sulphate was derived mainly from the sulphation of free DHA. The hydrolysis of DHA sulphate did not appear to make a significant contribution to the amounts of DHA synthesized under these conditions. The adrenal secretion of DHA and DHA sulphate by eight patients undergoing adrenal-ectomy was determined by measuring the concentrations of these compounds in samples of adrenal and peripheral venous blood taken simultaneously. In one patient secretion of DHA and DHA sulphate was equivalent whilst in the remainder there was much greater secretion of DHA.