Plasma concentrations of valproate during maintenance therapy in epileptic children

Summary A total of 20 children with various types of epilepsy were treated with valproate, 11 with monotherapy and 9 with valproate in combination with phenobarbitone, phenytoin, or carbamazepine. Valproate was given either every 8 or 12 h. At least two different dose levels were tried in each patient. The pharmacokinetics of valproate during the interval between doses was determined using a gas chromatographic technique. The clinical effect of the treatment was assessed by interviewing the parents.The plasma concentrations showed considerable fluctuation during the intervals between doses. The mean increase from pre-administration to peak level was 82% when the dose interval was 12 h, and 62% when it was 8 h. The mean plasma half-life of valproate, using a one-compartment model, was 10.9±1.3 h (mean±SD). The plasma half-life of valproate was decreased when the drug was combined with the other anti-epileptics. The calculated area under the concentration versus time curve was linearly related to dose, both in a single patient on four dose levels and when different patients were compared. The clinical effect of valproate monotherapy was best in patients with absences, usually good in myoclonus and less favourable in other types of epilepsy. For children with absences, the optimal dose range of valproate was between 20 and 40 mg/kg/24 h. In comparison, the myoclonic types of epilepsy needed a slightly higher dose level, between 30 and 60 mg/kg/24 h. In the latter group a therapeutic window seems to exist, since patients below and above the suggested dose levels were not well-controlled. Therapeutic monitoring of valproate does not appear meaningful when the drug is used as monotherapy. However, in combination therapy, determination of the plasma levels of all anti-convulsants used may be helpful. The large fluctuations of valproate during a dose interval must be taken into consideration when the clinical effects are analysed.Supported by the Swedish Medical Research Council (Project No. 522), Stiftelsen Margarethahemmet, and Sällskapet Barnavård     

Auditory toxicity effects of long-term cis-dichlorodiammineplatinum II therapy in genitourinary cancer patients

To determine the auditory toxicity effects of long-term cis-dichlorodiammineplatinum II therapy, pure tone hearing thresholds were measured prior to therapy and repeated before each subsequent treatment. CDDP was given by a slow intravenous drip method at a low dose of 1 mg/kg body weight, with 37.5 gm mannitol, once a week for six treatments and every 3 weeks thereafter. From a group of 173 genitourinary cancer patients treated, 50 male patients were selected who received at least 12 months of CDDP with no active conductive ear pathology, and whose audiograms obtained at baseline, 6th weeks, 26th weeks, and 52nd weeks of treatment were all available for comparison. Pure tone threshold levels deteriorated across time particularly by the 52nd week and at the higher frequencies. Threshold differences across time were statistically significant and within a linear trend. Of the 50 cases, 30% showed suspect or no ototoxicity, 26% mild, 32% moderate, 2% marked, and 4% showed severe ototoxic changes. Of the two cases who developed severe ototoxicity, one showed complete recovery. There was partial recovery in 26% and no recovery in 54%. Individual variability in susceptibility to and recovery from ototoxicity necessitates systematic audiometric monitoring throughout the therapy.     

Risks of BCG intralesional therapy: an experience with melanoma.

A nearly fatal allergic reaction to intratumor BCG injections was associated with a complete remission of recurrent malignant melanoma. Clinical course and histologic sections suggested both anaphylactic and Arthus reactions. The occurrence of reactions at BCG injection sites as well as at uninjected sites of tumor suggests common BCG and melanoma antigens. The management of events involved in this often fatal postimmunotherapy complication involves the early administration of parenteral fluids, antituberculous therapy, antihistamines, and possible steroids. The prophylactic use of antihistamines and an in-hospital administration of intralesional BCG immunotherapy are strongly suggested. In the future, prophylactic INH may prove to be both therapeutically efficacious and protective against infectious complications.     

Delayed transient neurologic toxicity due to tacrolimus: CT and MRI

We report a case of transient neurologic toxicity secondary to tacrolimus. The clinical and imaging findings are reported and their subsequent regression after interruption of therapy in the patient following a bone-marrow transplant is also described. The etiology of the neurotoxicity and its analogy with other immunosuppressant agents are discussed. Received: 18 June 1999/Accepted: 14 December 1999     

吡拉西坦佐治帕金森病的临床疗效

目的 :探讨吡拉西坦与多巴丝肼 (Ben Ldopa)联合治疗帕金森病 (PD)的疗效。方法 :3 7例PD患者在服用Ben Ldopa原剂量 1mo后 ,再在服用Ben Ldopa基础上增加吡拉西坦针剂 8～ 16g ,iv ,15～ 2 0d ;然后予吡拉西坦片剂 2g·d-1,po ,总疗程为 1mo。在应用吡拉西坦前后分别进行简易智力量表 (MMSE)评分、Webster功能评分 ,以及记录每日各例患者服用Ben Ldopa的剂量。结果 :吡拉西坦与Ben Ldopa联合应用后 ,MMSE评分均值提高≥ 4分的患者达 2 9例 ( 78 4% ) ,Webster评分均值减少≥ 3分者达 2 6例 ( 70 3 % ) ,Ben Ldopa剂量由联合治疗前的 ( 486± 2 2 3 )mg·d-1降至 ( 3 91± 2 2 3 )mg·d-1。结论 :吡拉西坦与Ben Ldopa联合应用于PD患者 ,可改善患者的认知功能 ,减轻运动障碍 ,降低Ben Ldopa日剂量     

Graves病患者131 碘治疗前后可溶性Fas水平变化及其临床意义

目的 探讨Graves病(GD)患者放射性131碘治疗前后可溶性Fas(sFas)的水平变化及其临床意义。方法 采用免疫酶联分析法(ELISA法),测定50例GD患者放射性131碘治疗前后外周血sFas的水平变化。结果 GD患者外周血sFas水平(3.41±1.58ng/ml)显著高于正常对照组(0.85±0.42ng/ml,P<0.001),放射性131碘治疗3个月后,血清sFas水平(1.95±2.03ng/ml)较治疗前显著下降(P<0.001),但仍高于正常水平(P<0.001)。sFas水平与FT3、FT4呈显著正相关(P<0.01),而与T3、T4、TSH、甲状腺球蛋白抗体(TGA-Ab)、甲状腺过氧化物酶抗体(TPO-Ab)、甲状腺摄碘率无明显相关性。结论 sFas异常增加参与GD发病过程,放射性131碘治疗GD具有免疫调节功能。     

腰痹舒治疗腰椎间盘突出症临床疗效分析

用中药腰痹舒治疗腰椎间盘突出症 3 1例 ,治愈 2 8例 ,有效 3例。治疗后随访 6～ 1 8个月 ,无 1例复发。与牵引、按摩、秋水仙碱内服对照组比较 ,中药疗效显著优于对照组 (P<0 .0 5 )。经 CT检查 ,腰痹舒治愈后椎间盘的后突压迫、粘连均有不同程度的解除。提出可根据症状、体征将腰椎间盘出症的腰腿痛分为 1 0级。作为判断病情和疗程的主要指标。其治疗宜通经、化瘀散寒为主。     

大黄及其复方治疗慢性肾功能衰竭的临床研究进展

本文将近10a中药大黄及其复方治疗慢性肾功能衰竭的一些报道做一归纳总结，证实做为纯中药，大黄在治疗慢性肾功能衰竭时有很好的作用，通过临床应用、实验研究、机制分析都已证明为治疗该病最有效药物之一。     

针灸抗早孕及引产催产研究进展

本文对近 5年针灸在抗早孕、引产催产方面的临床和实验研究的情况进行了总结。通过对 1 997年以来国内杂志相关文献进行综述 ,总结出在抗早孕方面 ,针灸主要应用于人流和药流的辅助治疗 ;在引产催产方面 ,针灸的应用与 5年前基本相同 ;在实验研究方面 ,主要是从电生理的角度验证和解释临床现象。针灸具有扩张宫颈、提高人流效果、镇静止痛、减少术中出血量等作用 ;针灸在药流中可加速排囊并提高完全流产率、减少出血、加快转经 ;针灸引产催产有效率较高 ,能促进宫颈成熟、缩短产程、减少产后出血量、减轻疼痛 ;实验研究发现针刺增强药流作用可能是通过调节子宫活动、改善妊娠相关组织血供而实现的