Rapid determination of anti-estrogens by gas chromatography/mass spectrometry in urine: Method validation and application to real samples

AbstractA fast screening protocol was developed for the simultaneous determination of nine anti-estrogenic agents (aminoglutethimide, anastrozole, clomiphene, drostanolone, formestane, letrozole, mesterolone, tamoxifen, testolactone) plus five of their metabolites in human urine. After an enzymatic hydrolysis, these compounds can be extracted simultaneously from urine with a simple liquid–liquid extraction at alkaline conditions. The analytes were subsequently analyzed by fast-gas chromatography/mass spectrometry (fast-GC/MS) after derivatization. The use of a short column, high-flow carrier gas velocity and fast temperature ramping produced an efficient separation of all analytes in about 4min, allowing a processing rate of 10samples/h. The present analytical method was validated according to UNI EN ISO/IEC 17025 guidelines for qualitative methods. The range of investigated parameters included the limit of detection, selectivity, linearity, repeatability, robustness and extraction efficiency. High MS-sampling rate, using a benchtop quadrupole mass analyzer, resulted in accurate peak shape definition under both scan and selected ion monitoring modes, and high sensitivity in the latter mode. Therefore, the performances of the method are comparable to the ones obtainable from traditional GC/MS analysis. The method was successfully tested on real samples arising from clinical treatments of hospitalized patients and could profitably be used for clinical studies on anti-estrogenic drug administration

Drug-Related Cardiotoxicity for the Treatment of Haematological Malignancies in Elderly.

Meyer Paul Hugo. Diderot oder die Ambivalenz der Aufklärung, Neumann, 1987. In: Recherches sur Diderot et sur l'Encyclopédie, n°4, 1988. pp. 164-165

Right phrenic nerve palsy following transcatheter radiofrequency current atrial fibrillation ablation: Case report

Phrenic nerve palsy (PNP) is a well-known complication of cardiac surgery or jugular/subclavian vein catheterization, presenting with cough, hiccups, dyspnoea/shortness of breath and, in some cases, ventilatory failure. Rarely, PNP is a complication of transcatheter radiofrequency ablation for atrial fibrillation. This report describes the case of a 72-year-old woman with a 2-year history of recurrent paroxysmal atrial fibrillation associated with occasional palpitations and shortness of breath who underwent routine transcatheter radiofrequency ablation. Three days after the procedure, the patient developed shortness of breath and progressive dyspnoea. Motor nerve conduction showed the absence of the right phrenic nerve compound motor action potential compared with the normal left side confirming the diagnosis of a right phrenic nerve palsy. This current case demonstrated the importance of undertaking an electrophysiological evaluation of phrenic nerve conduction after transcatheter radiofrequency ablation in patients presenting with palpitations and shortness of breath even if present a few days after the procedure

Basophil activation test for Staphylococcus aureus enterotoxins in severe asthmatic patients

Background: Several studies have shown an association between severe asthma and serum immunoglobulins E (IgE) against Staphylococcus aureus enterotoxins (SEs). SEs—the prototypes being types A (SEA), B (SEB) and toxic shock syndrome toxin 1 (TSST-1)—can induce both polyclonal and specific IgE responses. Objective: The aim of the study was to evaluate the ability of SEs to induce basophil activation in severe asthmatic patients using the basophil activation test (BAT). Methods: 57 severe asthmatic patients were enrolled. BAT in response to SEA, SEB and TSST-1 was performed in all patients, while serum IgE to SEA, SEB and SEC was available in 49 patients. BAT was considered positive when CD203c+ basophils to SEs were ≥5%, and the stimulation index (SI, ratio between % of CD203c+ basophils to SEs and to negative control) was >2. Two threshold values (>0.1 kU/L and >0.35 kU/L, respectively) were used to assess serum SEsIgE. Results: 36.8% of severe asthmatic patients had a BAT positive for at least one SE (BAT SEs+). Serum SEsIgE >0.35 kU/L (SEs IgE+) was associated with BAT SEs positivity. Among patients with negative skin prick test, 35% were BAT SEs+, 30% SEs IgE+, 55% BAT or IgE− SEs+. A negative correlation between SI of BAT to SEs and both clinical (ACT score) and functional parameters was observed, together with a positive correlation of BAT with asthma exacerbations. Conclusions: The positivity of BAT for SEs in a subgroup of severe asthmatic patients further supports the pathogenic role of Staphylococcus aureus in severe asthma