The effect of salbutamol on performance in endurance cyclists

The effect of salbutamol (S) on cycling performance was examined in 15 highly trained non-asthmatic male cyclists. A double-blind, randomized cross-over design was used with S or placebo (P) administered using a metered-dose inhaler and a spacer device 20 min before each testing session. The S dose was 400 μg (four puffs), which is twice the normal therapeutic level. Subjects were habituated to all the laboratory procedures in the week prior to actual data collection. The subjects performed four tests under S and P conditions on separate days over 2 weeks. These included measurement of maximal O₂ uptake (cycle ergometry) with assessment of pulmonary function before and after, a submaximal (90% of ventilatory threshold) square-wave work transition from a base of unloaded cycling, a 60-s modified Wingate test, and a simulated 20 km time trial. No significant differences were observed in any of the dependent variables related to aerobic endurance or cycling performance between the S and P conditions. These results support other findings that an acute dose (400 μg) of S has no performance-enhancing properties.     

Multiple-dose pharmacokinetics of epirubicin at four different dose levels: studies in patients with metastatic breast cancer

Summary Pharmacokinetic analysis of epirubicin and its metabolites epirubicinol and 7-deoxy-13-dihydro-epirubicinol aglycone during the first and the fourth courses of treatment was performed in 78 patients with metastatic breast cancer. The patients were treated every 3 weeks with epirubicin given as 10-min i.v. infusions at four different dose levels: 40, 60, 90 and 135 mg/m². In most cases (76 of 78 cases), plasma concentration-time curves fitted to a three-compartmental pharmacokinetic model. The terminal half-life of epirubicin was independent of dose and duration of treatment. Large interindividual differences were demonstrated (meant _1/2, 21.6±7.9 h; range, 10.6–69 h;n=110). In two subjects, extremely long half-lives and high serum bilirubin concentrations indicated impaired liver function. No correlation was found between the half-life and levels of liver alanine aminotransferase (ALAT) or serum creatinine. The metabolite epirubicinol appeared quickly after epirubicin administration and its half-lives were shorter than that of the parent compound (meant _1/2, 18.1±4.8 h; range, 8.2–38.4 h;n=105).Formation of the aglycone metabolite was delayed and the half-life of this metabolite was shorter than that of epirubicin (meant _1/2, 13±4.6 h; range, 2.7–29 h;n=104). The AUC of epirubicin and the total AUC (drug and metabolites) were linearly proportional to the dose, with the former value constituting two-thirds of the latter. A correlation was found between AUC and the plasma concentration of epirubicin at two time points (2 and 24 h after administration). The proposed model was AUC=9.44×c ₂+62.5×c ₂₄+157.7 (r=0.953).This work was supported by the Lundbeck Foundation, the Michaelsen Foundation and Farmitalia Carlo Erba Ltd.     

Integrating providers into quality improvement: a pilot project at one hospital

Brigham and Women's Hospital initiated a study of the quality of care centering on self-reporting of potential medical injuries by providers. The goal of the study is to decrease the incidence of such injuries through a continuous quality methodology that integrates providers into the identification phase and incorporates all hospital employees in the development of new practices. This article provides an overview of the investigation methodology and discusses the conceptual relationships between clinical epidemiological analyses and industrial quality improvement.     

Effect of acetylsalicylic acid on renal function in systemic lupus erythematosus

Summary Glomerular filtration rate (GFR;⁵¹Cr-EDTA clearance), serum creatinine concentration and urinary excretion of prostaglandins were measured in 8 patients with systemic lupus erythematosus (SLE) before and after 2 weeks of treatment with acetylsalicylic acid (ASA). ASA 65 mg/kg or up to 4 g/daily was given as a sustained release preparation. The serum salicylate concentration ranged from 0.3 to 1.6 mmol/l. Serum creatinine after 1 and 2 weeks and GFR after 2 weeks of ASA treatment showed no significant changes. There was a clearcut decrease in urinary excretion of prostaglandins PGE₂ and PGF₂, by 44% and 50%, respectively. It is concluded that therapeutic doses of ASA do not cause deterioration of GFR in patients with SLE and normal or moderately reduced renal function.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

The Safety of Atovaquone/Proguanil in Long-Term Malaria Prophylaxis of Nonimmune Adults

Background Data on the long-term safety of atovaquone/proguanil in nonimmune travelers are limited.
Methods An open-label study, involving 300 Danish soldiers stationed in Eritrea for 6 months was initiated. The subjects self-reported their symptoms on a post-travel questionnaire. The study compared the symptoms of compliers and noncompliers.
Results No serious adverse events occurred. Diarrhea, stomach pain, headache, cough, and loss of appetite were the most common symptoms reported. No case of Plasmodium falciparum malaria occurred.
Conclusions Atovaquone/proguanil was safe and well tolerated in this group of long-term nonimmune travelers.     

Lebensbedrohliche Infektionen in der Schwangerschaft

Zum Thema   Oftmals fatal verlaufende Infektionen in der Gravidit?t – vor allem postpartal – spielen immer noch trotz verbesserter Kenntnis zur Bakteriologie und Therapie, zur Infektionsprophylaxe und Hygiene eine gro?e Rolle. Als Folge der ver?nderten Immunlage in der Schwangerschaft kommt es h?ufig zu atypischen Verl?ufen, wodurch die Diagnostik erschwert wird. Auch zun?chst harmlos erscheinende Virusinfektionen k?nnen exazerbieren. Die einzelnen Krankheitsbilder (Sepsis, Amnioninfektionssyndrom, septischer Abort, Peritonitis und extragenitale Infektionen) sowie deren Diagnostik und Erreger werden besprochen. Besonders auf die antibiotische Kombinationstherapie wird eingegangen. Zusammenfassung   Schwangere mit Grundkrankheiten, Vorsch?den und Neigung zu rezidivierenden Genitalinfektionen sind in bezug auf lebensbedrohliche Infektionen vermehrt gef?hrdet. In Einzelf?llen bei hochpathogenen Erregern wie den Streptokokken der Gruppe A kann es nach Blasensprung oder operativen Eingriffen zu einer febrilen oder auch afebrilen t?dlichen Sepsis kommen. Die Beachtung der Vaginalflora, die Erkennung von Risikofaktoren und die frühzeitige und wirksame Antibiotikagabe verhindern sogenannte schicksalhafte Verl?ufe.