Sequential injection spectrophotometric determination of etilefrine hydrochloride

A simple, fast, economical and automated sequential injection spectrophotometric method for the determination of etilefrine hydrochloride is developed. The method is based on the condensation reaction of etilefrine hydrochloride with 4-aminoantipyrine in the presence of alkaline potassium hexacyanoferrate and the absorbance of the colored product measured at 503 nm. Aspiration order, flow rate, reaction coil diameter, reaction coil length, concentration of 4-aminoantipyrine and potassium ferricyanide, as well as aspiration volume of reagents and sample has been optimized. Using these optimized parameters, a linear relationship between the relative peak height and concentration was obtained in the range 1-20 mg l(-1). The detection limit (as 3sigma value) was 0.1 mg l(-1) and precision was 2.7% and 1.5% at 1 and 2 mg l(-1), respectively. This method is superior over previously reported ones in terms of linear range, short analysis time, high sample throughput, excellent reagent economy and minimum waste generation.     

Exposure misclassification as a result of free sample drug utilization in automated claims databases and its effect on a pharmacoepidemiology study of selective COX-2 inhibitors

PURPOSE: Free drug samples are widely used in clinical practice. We were concerned about free sample drug utilization as a source of misclassification in pharmacoepidemiology research using claims data that may result in biased effect estimates. METHODS: We investigated the magnitude of potential bias with sensitivity analyses based on a published study that examined cardiovascular risk associated with selective cyclooxygenase 2 (COX-2) inhibitors. We derived an estimate of free sample drug utilization with market data for rofexcoxib and calculated sensitivity of the exposure ascertainment method using claims data. We corrected the incidence rate ratio assuming the observed unexposed incidence rate was actually a weighted average rate of the truly unexposed and free sample drug users. The impact of exposure misclassification measured as the percentage change from a corrected to the reported crude incidence rate ratio was examined under a range of free sample drug utilization proportions and unexposed cohort sizes. RESULTS: The proportion of free sample drug utilization of all rofecoxib use in our base case scenario was 15.48%, resulting in sensitivity of 84.52% for exposure ascertainment. The magnitude of bias was an underestimation of the unadjusted incidence rate ratio by 0.03%. With a free sample drug utilization proportion of 1.48% and the same unexposed cohort size of 237 975 person-years, the underestimation was 0.003%. If the unexposed cohort were 975 person-years given a 15.48% proportion, the underestimation was 8.82%. CONCLUSIONS: In the pharmacoepidemiology study, we examined that uses claims data to ascertain drug exposure, our results suggest that adjustment for free sample drug utilization is probably not warranted.     

The impact of performance status on survival in patients of 80 years and older with vulvar cancer

OBJECTIVE: There are no data available on the impact of performance status on outcome in patients with vulvar cancer. It was the objective of this study to determine the impact of performance status on survival in a group of elderly patients. METHODS: A retrospective review of records of patients with vulvar cancer aged 80 years or greater and treated in a gynecological referral center was performed. Multiple clinical and pathological variables together with performance status were assessed and the impact on overall survival was determined both by univariate and multivariate analysis. RESULTS: Of 75 patients aged 80 years or older, 57 (76%) had standard treatment. The patients who had standard treatment were characterized by an earlier clinical stage and a better performance status compared with patients who had nonstandard treatment. When preoperatively available parameters of all patients were assessed in relation to survival in the total group, Eastern Cooperative Oncology Group (ECOG) performance status was the only independent prognostic indicator for survival. When all clinical and histopathological variables were assessed in the subgroup who had standard treatment, both ECOG performance status and extracapsular lymph node involvement were independent prognostic variables for overall survival. Age was not a significant prognostic variable. CONCLUSIONS: ECOG performance status is the only available pretreatment variable with independent prognostic value for survival in this group of elderly patients with vulvar cancer. These data show the importance of individualizing the treatment of patients with vulvar cancer. Performance status takes a more important place than age in the management process of these patients.     

Cost benefit analysis of early thrombolytic treatment with intracoronary streptokinase. Twelve month follow up report of the randomised multicentre trial conducted by the Interuniversity Cardiology Institute of The Netherlands.

The costs and benefits of early thrombolytic treatment with intracoronary streptokinase in acute myocardial infarction were compared in a randomised trial. All hospital admissions were recorded and the functional class was assessed at visits to the outpatient clinic during a 12 month follow up of 269 patients allocated to thrombolytic treatment and of 264 allocated to conventional treatment. Mean survival during the first year was calculated for patients with inferior and with anterior infarction and adjusted for impaired quality of life in cases where there were symptoms or hospital admission. In patients with inferior infarction mean survival was 337 days (out of a total follow up of 365 days) for patients allocated to thrombolytic treatment and 327 days for controls. Quality adjusted survival was seven days longer in the thrombolysis group (307 vs 300 days in controls). In patients with anterior infarction mean survival was significantly longer (35 days) in the thrombolysis group than in the control group as was quality adjusted survival (38 days) (304 vs 266 days in controls). The gain in life expectancy with thrombolytic treatment was 0.7 years for patients with inferior infarction, 2.4 years for patients with anterior infarction, and 3.6 years for the subset of patients with large anterior infarction who were admitted within two hours of the onset of symptoms. The costs of medical treatment, including medication, hospital stay, cardiac catheterisation, coronary angioplasty, and bypass surgery, in the first year follow up were higher inpatients allocated to thrombolytic treatment (an additional cost ofDfl 7000 in inferior and Dfl 9000in anterior infarction (1 pounds sterling approximately Dfl 3.3.)) than in conventionally treated patients. The additional costs per year of life gained were Dfl 10 000 in inferior infarction, Dfl 3 800 in anterior infarction, and only Dfl 1 900 in patients with large anterior infarction admitted within two hours of onset of symptoms.Intracoronary thrombolysis can be recommended as a cost effective treatment in patients with extensive anteroseptal infarction.     

THE PATHOLOGIC EFFECTS OF INTRAVENOUSLY ADMINISTERED SOLUBLE ANTIGEN-ANTIBODY COMPLEXES : I. PASSIVE SERUM SICKNESS IN MICE

The intravenous administration to mice of soluble antigen-antibody complexes in antigen excess resulted in a high incidence of glomerulonephritis and less frequently in endocarditis or arteritis. These lesions are present within 48 hours of the first of 3 injections and disappear within 2 weeks. The same pathological changes were produced with complexes prepared from either rabbit or chicken antibody. In the case of rabbit antibody, the severity of the glomerulonephritis was greater with the ovalbumin antiovalbumin system than with the BSA system. Anaphylaxis regularly occurred in mice given complexes prepared from rabbit antibody, but was not seen following administration of complexes prepared from chicken antibody. Pretreatment with cortisone diminished the severity of the glomerulo-nephritis and resulted in accumulation of amorphous, eosinophilic material within glomerular capillaries in mice injected with antigen-antibody complexes. The rabbit antibody used in these experiments failed to sensitize guinea pig skin to passive cutaneous anaphylaxis when injected in the form of soluble complexes. This indicates that these complexes do not dissociate to a detectable extent in vivo and thus favors the interpretation that complexes localize as such in the sites where tissue damage occurs. Chicken anti-mouse erythrocyte antibody produced hemolysis of mouse red cells in the presence of mouse complement. In contrast to a similar rabbit anti-serum, the hemolytic activity of the chicken antibody with mouse complement was very slight. This suggests that complement does not play an important role in the pathogenesis of these experimental lesions.     

Effects of halothane on myocardial high-energy phosphate metabolism and intracellular pH utilizing 31P NMR spectroscopy

Utilizing 31phosphorus nuclear magnetic resonance (NMR) spectroscopy, the authors tested the two hypotheses that the negative inotropic action of halothane is the result of: 1) myocardial intracellular acidosis, and 2) a decrease in myocardial high-energy phosphates. In isolated, paced, Langendorff-perfused rabbit hearts, halothane (1.5 vol %) dissolved in the coronary perfusate produced a 48 +/- 2% decrease (P less than 0.01) in left ventricular developed pressure. In contrast, halothane administration had no significant effect on myocardial intracellular pH (7.18 +/- 0.04 at control vs 7.21 +/- 0.02 during halothane). Halothane exposure decreased (P less than 0.01) the forward rate constant of the creatine kinase reaction by 32 +/- 6%, as measured using saturation transfer NMR, suggesting a decline in the rate of high-energy phosphate metabolism. This was further indicated by a concomitant decrease (P less than 0.05) in myocardial oxygen consumption (20 +/- 5%). During the halothane-induced reduction in left ventricular developed pressure, only small decreases in the myocardial steady state concentrations of phosphocreatine (7 +/- 1%; P less than 0.01) and beta ATP (12 +/- 4%; P less than 0.05), and an increase in Pi (18 +/- 6%; P less than 0.05) were observed. However, similar changes in steady-state high-energy phosphate metabolites were also measured in time-control hearts not exposed to halothane. These results indicate that the negative inotropic action of halothane is not mediated by myocardial intracellular acidosis. Moreover, these findings do not support the concept that the negative inotropic action of halothane is the result of a reduction in myocardial high-energy phosphates.