Late atrioventricular block after heart transplantation.

Bradyarrhythmia requiring permanent pacing after heart transplantation remains a common problem. Sinus node dysfunction is the most common indication, and late onset of atrioventricular (AV) block has rarely been reported. We report the case of a patient who developed advanced AV block at 41 months after transplantation. Right bundle branch block with progressive increase of QRS complex duration was noted in serial electrocardiograms. At the time of late AV block development, the patient did not have acute rejection and coronary angiogram was normal. The mechanism of late onset of AV block is unclear, but it may be caused by progressive conduction.     

Enantioselective metabolism and cytotoxicity of R-ifosfamide and S-ifosfamide by tumor cell-expressed cytochromes P450.

The anticancer prodrug ifosfamide (IFA) contains a chiral phosphorous atom and is administered in the clinic as a racemic mixture of R-IFA and S-IFA. Hepatic cytochrome P450 (P450) enzymes exhibit enantioselective preferences in the metabolism of R-IFA and S-IFA; however, the impact of this selectivity on P450-dependent anticancer activity is not known. Presently, the metabolism and cytotoxicity of R-IFA and S-IFA were determined in 9L gliosarcoma and Chinese hamster ovary tumor cells expressing an IFA-activating P450 enzyme and by in vitro steady-state kinetic analysis using cDNA-expressed P450 enzymes. Tumor cells expressing P450 enzyme CYP3A4 were the most sensitive to R-IFA cytotoxicity, whereas tumor cells expressing CYP2B1 or CYP2B6 were most sensitive to cyclophosphamide (CPA), an isomer of IFA. Correspondingly, CYP3A4-expressing cells and cDNA-expressed CYP3A4 metabolized R-IFA to yield the active, 4-hydroxylated metabolite at a 2- to 3-fold higher rate than they metabolized S-IFA or CPA. CYP2B cells and cDNA-expressed CYP2B enzymes metabolized CPA almost exclusively by 4-hydroxylation, whereas R-IFA and S-IFA were substantially converted to inactive, N-dechloroethylated metabolites. Further investigation revealed that CYP3A1, a rat enzyme, exhibited superior kinetic properties compared with the human enzyme CYP3A4, with R-IFA and S-IFA both metabolized with high catalytic efficiency by 4-hydroxylation and with a K(m) value of 200 microM, approximately 5-fold lower than CYP3A4. Based on these kinetic parameters and metabolic profiles, R-IFA is expected to exert greater anticancer activity than S-IFA or CPA against tumors that express CYP3A enzymes, whereas tumors expressing CYP2B enzymes may be more sensitive to CPA treatment.     

尼麦角林在脑血管病中的应用

尼麦角林是一种麦角生物碱衍生物，广泛应用于脑血管病患者认知障碍的治疗。多项临
床前研究显示，尼麦角林对于认知障碍的改善可能与以下因素有关：尼麦角林除能够改善脑循环，
促进神经递质释放外，还具有营养神经及抗氧化等作用。目前的研究认为，尼麦角林能够改善患者
卒中后抑郁相关的情绪障碍以及有效改善血管性痴呆，提高患者的日常生活能力。同时，尼麦角林具
有良好的安全性，目前暂无尼麦角林治疗导致纤维化或麦角中毒的研究报道。本文就尼麦角林在神
经系统的作用机制、临床疗效及安全性进行综述，以期为临床应用提供参考。     

Correlates of lifetime suicide attempts among individuals with affective disorders in a Chinese rural community.

The aim of this study was to compare the demographic and clinical characteristics of individuals with affective disorders who had attempted suicide at some time in their lives and those who had not made a suicide attempt. In a Chinese rural community, individuals with suicide attempt (N = 30) and those without suicide attempt (N = 166) were assessed with Present State Examination (PSE). Attempters had a significantly higher level of family economic status, higher rate of lifetime depressed mood and hopelessness, and delusions than nonattempters. The logistic regression models also indicated that depressed mood and hopelessness were the most important predictors of suicide attempts. No significant difference in treatment condition was found between attempters and non-attempters. Early identification and interventions focusing on reducing depressed mood, hopelessness, and controlling psychotic symptoms may be helpful in reducing the risk of suicide attempts among individuals with affective disorders residing in the community.     

Fat and water separation in balanced steady-state free precession using the Dixon method.

In this work the feasibility of separating fat and water signals using the balanced steady-state free precession (SSFP) technique is demonstrated. The technique is based on the observation (Scheffler and Hennig, Magnetic Resonance in Medicine 2003;49:395-397) that at the nominal values of TE = TR/2 in SSFP imaging, phase coherence can be achieved at essentially only two orientations (0 degrees and 180 degrees ) relative to the RF pulses in the rotating frame, under the assumption of TR < T2, and independently of the SSFP angle. This property allows in-phase and out-of-phase SSFP images to be obtained by proper choices of the center frequency offset, and thus allows the Dixon subtraction method to be utilized for effective fat-water separation. The TR and frequency offset for optimal fat-water separation are derived from theories. Experimental results from healthy subjects, using a 3.0 Tesla system, show that nearly complete fat suppression can be accomplished.