托吡酯治疗癫痫的临床研究

目的 :对托吡酯 (妥泰 )作为加用和单用治疗癫痫的疗效、剂量、加量速度、起效时间及副作用等进行观察研究。方法 :10 7例癫痫患者 ,83例采用加用妥泰治疗 ,2 4例单用妥泰治疗。结果 :共有 10 0例患者完成了 13周疗程的观察。妥泰加用治疗有效率达 80 .2 % ,单用治疗达 79.1% ,妥泰加用治疗在儿童组有效率为 77.5 % ,成人组为 83.3% ,妥泰加用及单用治疗对各型癫痫均有效 ,妥泰起效时间与加量速度显著相关。妥泰起效时间在 4～ 8周达高峰。 10 7例患者 ,副作用发生率为32 .7% ,均较轻。结论 :妥泰加用及单用治疗癫痫均有较好疗效 ,是一种广谱、安全、耐受性好的新型抗癫痫药物     

Evaluation of therapeutic efficacy of capecitabine on human breast carcinoma tissues and cell lines in vitro.

BACKGROUND: Capecitabine, an oral anticancer prodrug, was associated with relatively mild degrees of side effects, notably low myelosuppression. Previous studies demonstrated capecitabine monotherapy as safe and very useful for recurrent and advanced metastatic breast cancer patients who are generally associated with a poor prognosis. MATERIALS AND METHODS: Capecitabine and two conventional cytotoxic antineoplastic drugs (epirubicin and docetaxel) were employed in this study in order to compare their therapeutic antineoplastic effects. The tumour tissues obtained from 42 patients and breast carcinoma cell lines were treated with the chemotherapeutic agents above in vitro. Their efficacy was determined using ATP Bioluminescence assay which measures the metabolic rate, WST-1 assay that could quantify the inhibition of cell proliferation and immunohistochemical studies. The proapoptotic effects was examined using in situ apoptosis kit. RESULTS: Both solid tumour and cell lines treated by capecitabine as well as two drugs above demonstrated a significant decrement in metabolic and proliferation rates. However, capecitabine treatment resulted in significant increment of the number of the tumour cells undergoing apoptosis. CONCLUSION: Results of our present study demonstrated that capecitabine could be a useful agent against breast cancer cells with less side effects and its inhibition of cell proliferation of breast carcinoma is at least similar to that of two other commonly used cytotoxic drugs.     

妥泰添加及药物转换治疗儿童癫痫94例疗效观察

目的　观察妥泰 ( TPM)添加治疗儿童癫痫的疗效及癫痫发作完全控制后转换为 TPM单药治疗的可行性。方法　对 94例应用一线抗癫痫药控制不满意的患儿 ,其中部分性发作 ( PS) 5 2例 ,全身性发作 ( GS) 4 2例 ,在原用抗癫痫药 ( AEDs)的基础上加用 TPM 0 .5～ 1.0 mg/ kg.d,日 2次 ,口服 ,每 5～ 7d加量一次 ,直至达到目标剂量。治疗 12周后根据发作频率将疗效分为完全控制、显效、有效和无效。对发作完全控制后的癫痫患儿 8～ 12周后 ,逐渐减去其它抗癫痫药 ,转换为 TPM单药治疗。结果　 5 2例 PS患儿应用 TPM治疗后得到完全控制 2 9例 ,显效 10例 ,有效 6例 ,无效 7例 ,总有效率为 86 .5 %;42例 GS患儿治疗后完全控制 16例 ,显效 9例 ,有效 8例 ,无效9例 ,总有效率为 78.6 %;在完全控制发作的 2 9例 PS中 ,及 GS的 16例中 ,转换为单用 TPM治疗达 2个月以上尚未见发作的分别为 7例、4例。94例加用 TPM后 2 9例出现的不良反应 ,占 30 .9%,其中以食欲减退多见 ,其次为困倦及体重下降等 ,在加量期过后大多消失 ,治疗前后血、尿常规、肝、肾功能未发现有临床意义的改变。结论　 TPM是一种广谱、高效、安全的 AEDs,适用于小儿各型癫痫的联合和单药治疗。     

Topiramate Monotherapy for Partial Onset Seizures

Summary: Purpose: Evaluation of topiramate (TPM) as monotherapy in patients with uncontrolled partial onset seizures.
Methods: A total of 48 patients were evaluated in a doubleblind, parallel-group trial. During a 56-day baseline period, patients had at least eight partial onset seizures while being treated with one or two standard antiepileptic drugs (AEDs). After 1–2 weeks of open-label treatment with TPM 100 mg/day, patients were randomly assigned, in equal proportions, to receive double-blind therapy with TPM 100 or 1,000 mg/day in a 5-week conversion and an 11-week monotherapy period. The study endpoint was completion of 112 study days (success) or fulfillment of one or more exit criteria: doubling of average 28- day or highest 2-day baseline seizure rate, a generalized tonic-clonic seizure (GTCS) if none had occurred at baseline, or significant prolongation of generalized seizure duration.
Results: Time until exit was longer (p = 0.002) and success frequency was higher (p = 0.005) with TPM 1,000 as compared with 100 mg/day. Seizure-rate reductions of 50, 75, or 100% were achieved by 46, 25, and 13% of the 1,000-mg/day group, respectively, as compared with 13, 8, and 0% of the 100-mg/day group, respectively. Most adverse events (AE) were mild or moderate in severity.
Conclusions: Monotherapy with TPM 1,000 mg/day for partial onset seizures with or without secondarily generalized seizures was effective, with a favorable safety profile.     

Phenytoin Monotherapy for Epilepsy: A Long-Term Prospective Study, Assisted by Serum Level Monitoring, in Previously Untreated Patients

Summary: Of 31 previously untreated patients with grand mal and/or partial seizures referred to a neurological clinic and treated with phenytoin monotherapy, assisted by serum level monitoring, 26 have been followed up for a mean of 42 months. Seizures were completely controlled in 80%. Failure of optimum phenytoin monotherapy occurred in 12%. The degree of seizure control was significantly related to phenytoin serum levels. The success of monotherapy was probably related to availability of serum level monitoring and to the study of a previously untreated population with a relatively short history of epilepsy. The main reasons for failure of monotherapy were poor compliance and the presence of additional neuropsychiatric handicaps, which commonly occur together. The place for polytherapy in the event of failure of monotherapy has still to be defined.     

托吡酯单药治疗儿童癫癎的临床研究

目的:研究托吡酯单药治疗儿童癫癎的临床应用价值。方法:选择未用抗癫癎药物治疗,或既往用抗癫癎药物治疗,停药≥1个月的癫癎患儿250例。均给予托吡酯治疗,剂量由1mg/kg·d开始,每周增加1mg/kg·d,直至临床发作控制,或达4～8mg/kg·d。3个月后观察其疗效。并同时观察不良反应。结果:250例患儿共有241例完成全部随访。托吡酯单药治疗有效剂量为2～6mg/kg·d,癫癎发作频率减少≥50%者为199例(82.57%),≥75%者为147例(61%),减少100%者为96例(39.83%),<50%者为42例(17.43%)。最常见的不良反应为体重不增或降低、食欲减退、嗜睡、出汗减少、体温升高等。结论:托吡酯单药治疗儿童癫癎安全有效。     

Monotherapy with piperacillin/tazobactam versus combination therapy with ceftazidime plus amikacin as an empiric therapy for fever in neutropenic cancer patients

Between July 1993 and September 1996, 107 consecutive febrile episodes in 83 neutropenic cancer patients with a median age of 41 years were randomized to treatment either with piperacillin/tazobactam 4.5 g every 8 h i.v. or ceftazidime 2 g every 8 h plus amikacin 15 mg/kg i.v. per day. In the case of fever >38° C 48 h after initiation of the antibiotic therapy, vancomycin 500 mg every 6 h i.v. was added. The study population was at serious risk of a poor outcome, since 67% of the patients had leukemia or lymphoma, 19% of the febrile events occurred after autologous bone marrow or blood stem cell transplantation, the median total duration of neutropenia was 16 days, and the median neutrophil count at study inclusion was 0.09 × 10⁹/l. The two patient groups were comparable in terms of risk factors. Bacteremia was found in 37%, other microscopically documented infections in 16%, and clinically documented infections in 26% of the febrile episodes. Most (96) febrile episodes were evaluable for response. No significant difference was found between piperacillin/ tazobactam and ceftazidime plus amikacin in terms of success rate (81% versus 83%), empirical addition of vancomycin (42% versus 38%), median time to fever defervescence (3.3 versus 2.9 days) or median duration of antibiotic therapy (7.2 versus 7.4 days). No patient died from the infection. Both antibiotic regimens were well tolerated, the study treatment being stopped only in 1 patient because of toxicity (cutaneous allergy to piperacillin/tazobactam). On the basis of the 107 febrile events encountered, we conclude that piperacillin/tazobactam is a safe and effective monotherapy. To define the definitive value of piperacillin/ tazobactam as a monotherapy for febrile neutropenic patients a large randomized trial is warranted.