Trans-ACPD-induced Ca2+ signals in cerebellar Purkinje cells.

A combination of intracellular recording and fluorometric measurements of cytosolic calcium [( Ca2+]i) was used to locate changes in [Ca2+]i induced by the specific metabotropic glutamate receptor (mGluR) agonist trans-D,L-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD), in Purkinje cells of rat cerebellar slices. Under voltage-clamp conditions, application of t-ACPD (100 microM) induced an inward current accompanied by a large increase in [Ca2+]i located primarily in the soma but also, to a lesser degree, in restricted parts of the dendrites. In contrast, elevations of [Ca2+]i associated with calcium spikes were confined to the dendrites and inward currents of a similar amplitude induced by (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), an agonist of ionotropic glutamate receptors, did not raise [Ca2+]i.     

High incidence of anticardiolipin antibodies in relatives of patients with systemic lupus erythematosus

Anticardiolipin antibodies (aCL) were measured in the serum of 22 patients with systemic lupus erythematosus (SLE) and 101 of their first degree relatives. Four patients' sera (18%) were positive. Eight sera from relatives were strongly positive (7.9%). All 8 relatives came from different families, and only 3 of them were related to a positive positive proband. All 8 had clinical and/or other serological abnormalities, compared with only 30% of the aCL negative relatives (p less than 0.05). There were no reports or evidence of thrombosis, thrombocytopenia or spontaneous abortion among the aCL positive relatives. Our data indicate a strikingly higher incidence of aCL among relatives of lupus patients compared with controls. This may be associated with an increased incidence of abnormal clinical or serological findings in these individuals, and constitute a feature of a genetic predisposition to SLE.     

瑞芬太尼在产科麻醉镇痛中的应用

瑞芬太尼是一种新型的超短效阿片药物,它的出现使得麻醉可控性和预见性得到了优化。最近有更多的研究将它用于产科的麻醉与镇痛,为产科麻醉用药带来了新的选择。本文将就瑞芬太尼近年来在产科麻醉与镇痛方面的临床研究进展进行探讨。     

Definitive radiotherapy for medically inoperable early-stage serous and clear cell uterine carcinoma

High-risk, early-stage endometrial cancer is optimally treated by hysterectomy followed by adjuvant radiotherapy. In 1%–9% of cases, the patient is medically unfit or personally unwilling to undergo primary surgery, and definitive radiotherapy may be offered as an alternative definitive therapy. Although several series have reported excellent intrauterine control and disease-specific survival for endometrioid histology, few outcome data are available for patients with serous or clear cell histology treated with radiotherapy alone. We herein describe one case each of early-stage, medically inoperable serous/clear cell histology endometrial cancer treated with definitive radiotherapy. Treatment was well tolerated by both patients, and neither patient required a treatment break. Acute toxicity consisted of self-limited cystitis in one patient. One patient was without evidence of disease progression at 54 months after radiotherapy.     

Pathway inhibition: emerging molecular targets for treating glioblastoma

Insights into the molecular pathogenesis of glioblastoma have not yet resulted in relevant clinical improvement. With standard therapy, which consists of surgical resection with concomitant temozolomide in addition to radiotherapy followed by adjuvant temozolomide, the median duration of survival is 12-14 months. Therefore, the identification of novel molecular targets and inhibitory agents has become a focus of research for glioblastoma treatment. Recent results of bevacizumab may represent a proof of principle that treatment with targeted agents can result in clinical benefits for patients with glioblastoma. This review discusses limitations in the existing therapy for glioblastoma and provides an overview of current efforts to identify molecular targets using large-scale screening of glioblastoma cell lines and tumor samples. We discuss preclinical and clinical data for several novel molecular targets, including growth factor receptors, phosphatidylinositol-3 kinase, SRC-family kinases, integrins, and CD95 ligand and agents that inhibit these targets, including erlotinib, enzastaurin, dasatinib, sorafenib, cilengitide, AMG102, and APG101. By combining advances in tumor screening with novel targeted therapies, it is hoped that new treatment options will emerge for this challenging tumor type.     

Do women with epilepsy have increased frequency of menstrual disturbances?

PROBLEM: Menstrual disorders, reduced fertility and sexual problems seem to be more frequent in women with epilepsy than in the general population. Most investigations concerning menstrual disturbances in epilepsy patients, however, are small and based on selected materials. We therefore wanted to investigate the frequency of menstrual disturbances in a large, unselected population of epilepsy patients. METHODS: A retrospective, questionnaire study of a cohort of female outpatients, aged 18-45 was conducted. Each patient chose a close female friend who served as control, to optimise matching regarding age and lifestyle. RESULTS: Answers were received from 265 patients and 142 controls. Menstrual disturbances were more frequent in patients with epilepsy (48.0%) than in controls (30.7%) (P=0.004). Menstrual disturbances were more frequent in patients on polytherapy versus monotherapy (P=0.049) and more frequent in patients with high seizure frequency (>5seizures/year) compared to patients with a lower seizure frequency or those seizure free (P=0.006). The frequency of menstrual disturbances was higher in patients on valproate compared to carbamazepine monotherapy (P=0.045). CONCLUSION: This investigation confirms that women with epilepsy have an increased frequency of menstrual disturbances compared to women without epilepsy. In women with high seizure frequency and in those on polytherapy, the frequency of menstrual disturbances are further increased. The highest frequency of menstrual disturbances occurred in women using valproate.