The management of epilepsy in pregnancy

While most women with epilepsy can expect a normal pregnancy outcome, epilepsy remains a significant contributor to both maternal and perinatal morbidity. Pre-pregnancy planning must address reliable contraception and optimisation of antiepileptic drug (AED) regimens to minimise teratogenic risk while maintaining seizure control. The most recent data from the AED registries regarding malformations is presented in this review, as is the limited data on the newer AEDs and studies linking neurocognitive outcomes to AED exposure. During pregnancy, important considerations include; therapeutic drug monitoring, surveillance for obstetric complications and vigilance for seizures during the intrapartum and postpartum period.     

Primary therapy for adults with T-cell lymphoblastic lymphoma with hematopoietic stem-cell transplantation results in favorable outcomes.

BACKGROUND: Controversy exists regarding the role of high-dose therapy followed by stem-cell transplant (SCT) in the treatment of T-cell lymphoblastic lymphoma (T-LBL). We conducted an intention-to-treat analysis of the strategy of SCT as definitive treatment of T-LBL. PATIENTS AND METHODS: From July 1987 to March 2005, 34 adults with T-LBL were diagnosed and treated in British Columbia. Treatment, before planned SCT, consisted of a non-Hodgkin's lymphoma (NHL)/acute lymphoblastic leukemia hybrid chemotherapy protocol (28 patients) or a standard NHL chemotherapy regimen (six patients). RESULTS: Median follow-up of the 23 surviving patients is 51 months (range 13-142 months). Twenty-nine proceeded to SCT (four allogeneic, 25 autologous). For all 34 patients, 4-year overall survival (OS) and event-free survival (EFS) are 72% and 68%, respectively. For patients proceeding to SCT, the 4-year OS and EFS are 79% and 73%, respectively. All patients who received allografts are alive without disease at 38-141 months since diagnosis. For patients who received autografts, the 4-year EFS is 69%. Bone marrow involvement was a significant prognostic factor predicting for a worse survival (P = 0.02). CONCLUSION: A treatment strategy for adults with chemosensitive T-LBL that includes planned consolidation with SCT in first response produces favorable long-term outcome.     

Relationship of cross-brain oxygen content difference, cerebral blood flow, and metabolic rate to neurologic outcome after near-drowning.

We evaluated the relationship of global cerebral blood flow, cross-brain oxygen content difference, cerebral metabolic rate for oxygen, intracranial pressure, and cerebral perfusion pressure to functional neurologic outcome in 12 comatose children on 2 consecutive days after near-drowning. Five children survived with functional neurologic outcome; five died and two survived with severe neurologic damage. Children who survived with functional neurologic outcome had a significantly higher cross-brain oxygen content difference (7.89 +/- 2.62 vs 3.91 +/- 1.59 ml/dl; p = 0.028) at 24 hours and a higher cerebral metabolic rate for oxygen 48 hours after admission (3.19 +/- 2.86 vs 0.96 +/- 0.45 ml/100 gm per minute; p = 0.030) compared with those who died or survived in a damaged state. There were no significant differences in global cerebral blood flow, intracranial pressure, and cerebral perfusion pressure between groups at either 24 or 48 hours. Our preliminary data suggest that a higher cross-brain content difference value is an important early variable associated with functional neurologic recovery after near-drowning. However, a single cross-brain oxygen content difference value must be interpreted with caution because considerable variability may occur among patient groups.     

Relapse prevention and maintaining abstinence in older adults with alcohol-use disorders

Although older adults are sometimes believed to have the lowest rates of alcohol abuse as an age cohort, the prevalence of alcohol use and abuse in this group is clearly underestimated. The under-diagnosis of alcohol abuse is due, in part, to the facts that the effects of alcohol use among older adults tend to be less clearly visible than among other age groups and that older adults are less likely to seek treatment than younger age groups. An additional challenge to diagnosis may be a lack of previous alcohol abuse by the patient, as approximately one-third of older adults with alcohol-use problems first develop their drinking problem after the age of 60 years. With a demographic shift that is expected to increase the number of older adults with alcohol problems, the awareness and understanding of this problem becomes increasingly important. Under-diagnosis of problem drinking in older adults is particularly unfortunate because the risks associated with alcohol abuse and relapse for the elderly are significant. Relapse, or the return to drinking following abstinence, may follow situations that are of particularly high risk for older adults. These include situations related to anxiety, interpersonal conflict, depression, loneliness, loss or social isolation. By helping patients to monitor these high-risk situations, to identify strategies that have been successful in promoting abstinence in the past, and to become engaged in treatment, relapse may be avoided and abstinence maintained. Treatments such as cognitive-behavioural therapy, group and family therapies and self-help groups are just as effective for older adults as they are for other age groups. In fact, group and family therapies and self-help groups may be of particular benefit to older adults because of the emphasis on social support. Medicinal adjuncts are also equally effective in the elderly, but strict compliance and careful monitoring of adverse effects are especially important in patients who take multiple medications. Because of their benign adverse effect profiles, naltrexone and acamprosate are particularly good pharmacological agents for relapse prevention in older adults.     

PDGF(BB) increases myocardial production of VEGF: shift in VEGF mRNA splice variants after direct injection of bFGF, PDGF(BB), and PDGF(AB)

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis. We hypothesized that a combination of recombinant angiogenic proteins might induce myocardial VEGF production and cause a shift in the mRNA signal produced. MATERIALS AND METHODS: The left ventricles of New Zealand white rabbits were injected with 500 microL of saline, basic fibroblast growth factor (bFGF), platelet-derived growth factor-AB (PDGF(AB)), platelet-derived growth factor-BB (PDGF(BB)), bFGF + PDGF(AB), or bFGF + PDGF(BB). Myocardial VEGF production was analyzed by ELISA while mRNA splice variants were analyzed by RT-PCR 3 and 7 days after injection. RESULTS: PDGF(BB) alone caused the most pronounced induction of VEGF. Three days after injection the induction of VEGF by PDGF(BB) was significant compared to all treatment groups, except the bFGF + PDGF(BB) group. Induction of VEGF by PDGF(BB) was associated with a decrease in mRNA production of VEGF(121) within the myocardium. CONCLUSIONS: Injection of PDGF(BB) induces significant production of VEGF within the myocardium. This induction of VEGF production is associated with a shift toward other, less soluble forms of VEGF. These findings may allow more precise regulation of the myocardial response to therapeutic angiogenesis.     

Atubular glomeruli in a rat model of polycystic kidney disease

BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) is associated with a progressive decline in glomerular filtration rate (GFR) that often leads to end-stage renal disease. The basis for this decline in GFR is poorly understood. METHODS: Glomeruli in heterozygous Han:SPRD rats with ADPKD and their normal litter mates were studied by light microscopy, using serial sectioning techniques. The connections of the renal corpuscles to proximal tubules were classified as normal, atrophied, or absent (atubular glomerulus). Renal corpuscles also were examined by scanning electron microscopy. Single nephron glomerular blood flows were determined using microspheres. RESULTS: In the kidneys of six-month-old rats with ADPKD, 50% of the glomeruli were atubular and another 26% were associated with atrophied neck segments; these glomeruli were most often smaller in size than normal. About 16% of the glomeruli were hypertrophied and had normal connections to proximal tubules. Sclerotic changes in cystic kidney glomeruli were usually mild or moderate, and belied the failure of glomerular function. Glomerular blood flow in the cystic kidneys averaged half of normal and was markedly heterogeneous; the majority of small glomeruli displayed very low blood flows and a few showed relatively high blood flows. Fewer glomerular abnormalities were found in rats treated for five months with potassium citrate in their drinking water. CONCLUSIONS: The diminished GFR in the rat with ADPKD can be accounted for largely by the formation of atubular glomeruli. Compensatory glomerular hypertrophy also is present and may contribute to the progression of the renal disease.     

阿德福韦双酯治疗拉米夫定耐药的慢性乙肝患者时出现的耐药问题

背景:阿德福韦双酯(ADV) 是一种有效治疗野生型和耐拉米夫定乙肝病毒(HBV)的核苷酸类药物。在使用核苷酸类药物治疗慢性乙肝时,当治疗时间为 48、96、144周时,耐ADV变异体出现的累积发生率分别为0、 0．8-3％和0-5．9％。目的:研究67例对拉米夫定耐药且接受ADV治疗的慢性乙肝患者耐ADV病毒变异体的表型和基因型特点。方法:HBV DNA含量采用实时定量PCR技术。ADV变异体检测采用基质辅助激光解吸电离／飞行时间质谱为基础的基因分型     

The effect of discharge voltage on renal injury and impairment caused by lithotripsy in the pig

The present study was designed to determine the effects of shock wave voltage (kV) on lesion size and renal function induced by shock wave lithotripsy (SWL) in the 6- to 8-wk-old pig. Each SWL-treated pig received 2000 shock waves at 12, 18, or 24 kV to the lower pole calyx of one kidney. A group of sham SWL pigs served as time controls. Bilateral GFR, renal plasma flow (RPF), and para-aminohippurate (PAH) extraction were measured 1 h before and 1 and 4 h after SWL in all treated and sham animals. The kidneys were removed at the end of each experiment for morphometric analysis. The SWL-induced lesion increased significantly in size as shock wave energy was increased from 12 to 24 kV. PAH extraction, a measure of tubular function, was not significantly affected at 12 kV, was transiently reduced at 18 kV, and was reduced for the duration of the experiment at 24 kV. GFR and RPF, however, were significantly and similarly reduced at the 1 h post-SWL period at all three kilovolt levels. At the 4-h post-SWL period, both GFR and RPF had returned to baseline levels. Lesion size and tubular injury were correlated with changes in kilovoltage, while changes in renal hemodynamics were already maximal at the lowest discharge voltage. These findings suggest that renal microvessels are highly sensitive to shock waves and that frank injury to tubules and vessels may be more closely related to discharge energy than is renal blood flow.