Venous thromboembolism prevention with low molecular weight heparin may reduce hemorrhagic transformation in acute ischemic stroke

Background: Subcutaneous heparin at a prophylactic dose (SHPD) is a rather common treatment in ischemic stroke, but whether it confers an increased risk of hemorrhagic transformation of cerebral infarct (HT) and whether its reduction or discontinuation favors HT regression are presently poorly understood. Methods: Two samples of ischemic stroke patients with a cerebral lesion diameter 65 3 cm on brain CT scan, admitted over 7 years to our stroke unit, were retrospectively examined: (1) patients treated or not treated with SHPD (enoxaparin 4000 U/day), with subsequent assessment of possible HT appearance (N = 267, mean age 75.9 \ub1 12.8 years) and (2) patients treated with SHPD, with HT and subsequent reduction/discontinuation or maintenance of the initial dose, and subsequent assessment of HT evolution (N = 116, mean age 75.7 \ub1 11.1 years). HT severity was quantified according to the ECASS study (HT score). Results: In the first sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and other possible confounders, SHPD was inversely associated with HT appearance (hazard ratio 0.62, 95% CI 0.39\u20130.98, P = 0.04). In the second sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and initial HT severity, SHPD reduction/discontinuation had an inverse effect on both HT score improvement (odds ratio 0.42, 95% CI 0.18\u20130.99, P = 0.049) and HT improvement according to neuroradiological reports (odds ratio 0.34, 95% CI 0.14\u20130.82, P = 0.015). Conclusions: This retrospective study suggests that SHPD may play a protective role in HT appearance and evolution, which requires verification by a randomized clinical trial

CYP2D6-related oxidation polymorphism in Italy

The distribution of the oxidation polymorphism related to cytochrome CYP2D6 (debrisoquine type) was determined in 246 healthy Italian volunteers. Phenotyping was based on HPLC determination of the dextrometorphan/dextrorphan concentration ratio (metabolic ratio) in urine samples collected over an 8 h interval following a single oral 30 mg dose of dextromethorphan hydrobromide. Urinary excretion of dextromethorphan showed a wide interindividual variability, ranging from < or = 0.04 to 3.9% and from 0.5 to 79.6% of the dose, respectively. Metabolic ratios ranged from < or = 0.001 to 6.6. Eleven of the 246 subjects showed a metabolic ratio greater than 0.30, indicating that 4.5% of the population could be ascribed to the poor metabolizer status. The frequency of the poor metabolizer phenotype in this population is within the range described for other Caucasian ethnic groups

Lamotrigine and valproate pharmacokinetics interactions in epileptic patients

Lamotrigine (LTG, 3,5-diamino-6- (2,3-dichlorphenyl)-l,2,4-triazine) is an antiepileptic drug used mainly for partial and generalized seizures. The efficacy of LTG in treating resistant partial seizures was optimized when it was combined with valproate (VPA). The aim of this study was to investigate the influence of VPA on LTG pharmacokinetics in epileptic patients. Methods: 38 patients were randomly divided into two groups, one given LTG (n=18) and the other given LTG+VPA(n=20). The first group consisted of 10 females (32.50±12.46 years old, 67.80 ± 15.18 kg) and 8 males (24.88±8.92 years old, 69.88±11.41 kg) and the second group consisted of 9 females (28.33±6.52 years old, 62.89 ± 13.28 kg) and 11 males (37.64± 10.43 years old, 85.64 ± 15.4 kg). Patients were either administered an oral dose of LTG (157 ±74 mg/day) or LTG+VPA (150±83.11 mg/day & 774±330 mg/day respectively). LTG steady state serum concentrations were determined 1.5-8 h post dose. Analyses were performed by a validated HPLC method. Results: LTG serum concentrations were increased significantly from 4.67±3.66 and 9.56±5.27 µg/ml by concomitant administration of VPA. Discussion: The inhibition of LTG metabolism by VPA was shown to have a marked effect on LTG kinetics. This inhibitory effect was complicated further by inter-patients variation in body weight and gender. This emphasizes the importance of continuous monitoring of LTG serum concentrations on an individual basis. Accordingly, if the use of potentially interacting drugs cannot be avoided, adverse reactions can be minimized by dose adjustments guided by careful monitoring of clinical response and measurement of LTG serum concentrations

Eosinophils in Human Disease

SCOPUS: ch.binfo:eu-repo/semantics/publishe