Human leukocyte myeloperoxidase has been purified to homogeneity by a three-step procedure which includes dialysis of a granule extract against low-salt buffer. Sephadex G-75 chromatography, and carboxymethylcellulose chromatography. The final product was homogeneous when examined by acid polyacrylamide gel electrophoresis and sedimentation equilibrium ultracentrifugation. The molecular weight determined by the latter procedure was 118000. With or without reduction of the protein by 2-mercaptoethanol, subunits were formed which migrated as a single band after sodium dodecyl sulfate gel electrophoresis. With reduction, the molecular weight of the apparently identical subunits was 59000, and 42000 without reduction. Other general properties of human leukocyte myeloperoxidase, including amino acid composition, amino terminal sequence analysis, and absorption spectra, are also reported. Myeloperoxidase, in the presence of hydrogen peroxide and chloride ion, and no other substrate, autoinactivates. After completion of the inactivation reaction, several oxidizable amino acids in the enzyme are modified, and the absorption peak at 430 nm disappears. The presence of a substrate of the myeloperoxidase system (alpha-1-proteinase inhibitor), or of high concentration of chloride ion, completely protects the enzyme from autoinactivation.

MK-7246, an antagonist of the chemoattractant receptor on T helper type 2 (Th2) cells, is being developed for the treatment of respiratory diseases. In a first-in-human study, we investigated whether genetic polymorphisms contributed to the marked intersubject variability in the pharmacokinetics of MK-7246 and its glucuronide metabolite M3. Results from in vitro enzyme kinetic studies suggested that UGT2B17 is probably the major enzyme responsible for MK-7246 metabolism in both the liver and the intestine. As compared with those with the UGT2B17*1/*1 wild-type genotype, UGT2B17*2/*2 carriers, who possess no UGT2B17 protein, had 25- and 82-fold greater mean dose-normalized values of area under the plasma concentration–time curve (AUC) and peak concentration of MK-7246, respectively, and a 24-fold lower M3-to-MK-7246 AUC ratio. The apparent half-life of MK-7246 was not as variable between these two genotypes. Therefore, the highly variable pharmacokinetics of MK-7246 is attributable primarily to the impact of UGT2B17 genetic polymorphisms and extensive first-pass metabolism of MK-7246.

Editorials Postpneumonectomy empyema The development of an empyema following pneumonectomy is a devastating complication, especially if associated with an underlying fistula. Whilst the perioperative mortality of pneumonectomy overall is now less than 7%1-3, this rises to around 25% when complicated by empyema4-6, and about 50% when associated with fistula56. In addition, there is the morbidity and social cost of long-term drainage, chronic sepsis and, further, often multiple operations. Whilst in the past some authors have suggested that there might be a 'silver lining' in the form of improved long-term survival7'8, this is now discounted46.

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Objective: To assess the effectiveness of subxiphoid pericardiostomy in the treatment and diagnosis of pericardial effusions. Methods: 368 patients who underwent subxiphoid pericardiostomy and tube drainage for cardiac tamponade, moderate to severe pericardial effusion, or suspicious bacterial aetiology were retrospectively analysed. Biopsies of the pericardium and fluid samples for diagnostic tests were obtained from each patient. Results: The mean age of the patients was 38.4 years, and the male to female ratio was 220:148. The pericardial effusion was classified by echocardiography as severe in 53% of the patients, moderate in 43%, and mild in 4%. The incidence of cardiac tamponade was 25%. Myocardial injury requiring sternotomy occurred as an operative complication in 0.8% of the patients and recurrent effusion necessitating further surgical intervention developed in 10% of patients. Histopathological examination and the polymerase chain reaction of specimens of pericardium and fluid were helpful for establishing a diagnosis in 90% of patients with malignancy and 92% of patients with tuberculous pericarditis. The overall 30 day mortality rate was 0.8%. Patients were followed up for at least one year. Pericardial constriction requiring pericardiectomy developed in 3% of the patients. Conclusions: Pericardial effusions of various causes can be safely, effectively, and quickly managed with subxiphoid pericardiostomy in both adults and children.