An assessment of rufinamide as an anti-epileptic in comparison with other drugs in clinical development

This article evaluates rufinamide, a new anti-epileptic drug (AED) in Phase III development. This review is done against the background of therapeutic challenges of epilepsy, old established AEDs, newly introduced AEDs and AEDs in clinical development. Pharmacological properties of 12 AEDs in clinical trials (Phases I - III) are compared: ADCI, AWD 131-138, DP-VPA, ganaxolone, levetiracetam, losigamone, pregabalin, remacemide hydrochloride, retigabine, rufinamide, soretolide and TV1901. One of these, levetiracetam has been approved in the USA and is waiting approval in other countries. The protective index of rufinamide, as shown in rodent models of epilepsy, is much higher than that of most common AEDs. Features which make it a desirable AED are: (i) a broad spectrum of anti-epileptic actions including both partial and symptomatic generalised epilepsy; (ii) a statistically significant reduction in seizure frequency in clinical trials; (iii) efficacy and safety shown in a broad range of age groups including children and the elderly; (iv) rapid oral absorption enabling quick titration to effective dose and (v) a benign adverse event profile. Most of the events did not lead to discontinuation in clinical trials. These features offer considerable advantages over the existing anti-epileptic drugs. It is one of the two drugs in development which have reached Phase III and is expected to be approved by the year 2001 - 2002.     

Radiolabeling of new generation magnetic poly(HEMA–MAPA) nanoparticles with 131I and preliminary investigation of its radiopharmaceutical potential using albino Wistar rats

In this study, N ‐methacryloyl‐l ‐phenylalanine (MAPA) containing poly(2‐hydroxyethylmethacrylate) (HEMA)‐based magnetic poly(HEMA–MAPA) nanobeads [mag‐poly(HEMA–MAPA)] were radiolabeled with ¹³¹I [¹³¹I‐mag‐poly(HEMA–MAPA)], and the radiopharmaceutical potential of ¹³¹I‐mag‐poly(HEMA–MAPA) was investigated. Quality control studies were carried out by radiochromatographic method to be sure that ¹³¹I binded to mag‐poly(HEMA–MAPA) efficiently. In this sense, binding yield of ¹³¹I‐mag‐poly(HEMA–MAPA) was found to be about 95–100%. In addition to this, optimum radiodination conditions for ¹³¹I‐mag‐poly(HEMA–MAPA) were determined by thin‐layer radiochromatography studies. In addition to thin‐layer radiochromatography studies, lipophilicity (partition coefficient) and stability studies for ¹³¹I‐mag‐poly(HEMA–MAPA) were realized. It was determined that lipophilicities of mag‐poly(HEMA–MAPA) and ¹³¹I‐mag‐poly(HEMA–MAPA) were 0.12 ± 0.01 and 1.79 ± 0.76 according to ACD/logP algorithm program, respectively. Stability of the radiolabeled compound was investigated in time intervals given as 0, 30, 60, 180, and 1440 min. It was found that ¹³¹I‐mag‐poly(HEMA–MAPA) existed as a stable complex in rat serum within 60 min. After that, biodistribution and scintigraphy studies were carried out by using albino Wistar rats. It was determined that the most important ¹³¹I activity uptake was observed in the breast, the ovary, and the pancreas. Scintigraphy studies well supported biodistribution results. Copyright © 2013 John Wiley & Sons, Ltd.     

Sequelae and survivorship in patients treated with 131I-MIBG therapy

Background:

¹³¹I-meta-iodobenzylguanidine (¹³¹I-MIBG) has been in therapeutic use since 1980s. Newer treatment modalities are emerging for neuroendocrine tumours (NETs) and chromaffin cell tumours (CCTs), but many of these do not yet have adequate long-term follow-up to determine their longer term efficacy and sequelae.

Methods:

Fifty-eight patients with metastatic NETs and CCTs who had received ¹³¹I-MIBG therapy between 2000 and 2011 were analysed. Survival and any long-term haematological or renal sequelae were investigated.

Results:

In the NET group, the overall median survival and median survival following the diagnosis of metastatic disease was 124 months. The median survival following the commencement of ¹³¹I-MIBG was 66 months. For the CCT group, median survival had not been reached. The 5-year survival from diagnosis and following the diagnosis of metastatic disease was 67% and 67.5% for NETs and CCTs, respectively. The 5-year survival following the commencement of ¹³¹I-MIBG therapy was 68%. Thirty-two patients had long-term haematological sequelae: 5 of these 32 patients developed haematological malignancies. Two patients developed a mild deterioration in renal function.

Conclusion:

Long follow up of ¹³¹I-MIBG therapy reveals a noteable rate of bone marrow toxicities and malignancy and long term review of all patients receiving radionuclide therapies is recommended.     

日本福岛核事故后北京地区土壤放射性水平监测

目的检测日本福岛核事故后北京地区土壤中放射性核素的含量,评价此次核事故对北京地区土壤造成的放射性污染程度。方法启动核应急监测体系,使用高纯锗γ谱仪测量系统对北京地区的28个土壤样品中放射性核素226Ra、232Th、40K、131I和137Cs的比活度进行了监测。结果 28个土壤样品中未检测到人工放射性核素131I,24个样品中检出人工放射性核素137Cs,最高值为6.01Bq/kg(昌平200号院外土壤样品);所检土壤样品中放射性核素226Ra、232Th、40K、137Cs的比活度平均值分别为16.76、27.12、451.12和1.24Bq/kg,均低于20世纪80年代北京土壤中放射性水平。结论土壤中137Cs主要来源于既往核事件和核试验的贡献,受此次福岛核事故的影响非常微小,不会对该地区居民产生明显的健康影响。     

99mTc-depreotide受体显像在分化型甲状腺癌转移灶诊断中的临床应用

目的：探讨99mTc-depreotide受体显像在分化型甲状腺癌转移灶诊断中的临床应用价值。方法：67例接受131I治疗的分化型甲状腺癌（DTC）随访患者,以甲状腺球蛋白增高阈值〉10ng/ml为标准分为实验组（n=32）和对照组（n=35）,常规行131I全身扫描（WBS）,同时以99mTc-depreotide作为显像剂行肿瘤生长抑素受体显像。以核素显像感兴趣区（ROI）技术,测定肿瘤/非肿瘤（T/NT）比值,进行定量分析。比较99mTc-depreotide受体显像及131I全身显像在诊断甲状腺癌转移灶灵敏性、特异性、准确性的差异。结果：实验组99mTc-depreotide肿瘤受体显像和131I全身显像T/NT比值分别为4.45±0.44和2.14±0.51;对照组T/NT比值分别为1.13±0.21和1.42±0.16。两种方法的灵敏性、特异性、准确性分别为95.45%、50.00%、87.04%和81.82%、80.00%、81.48%。结论：99mTc-depreotide肿瘤受体显像可提高诊断分化型甲癌转移灶灵敏性,但特异性低于131I全身显像,99mTc-depreotide肿瘤受体显像可作为Tg、131I全身显像等分化型甲癌随访常规方法的有效补充。     

A Preliminary Assessment of the Consequences for Inhabitants of the UK of the Chernobyl Accident

Summary

The accident with the nuclear power reactor at Chernobyl in the USSR resulted in the release of substantial quantities of radioactive material and subsequent increases in radioactivity in the environment in many countries. In this paper the situation in the UK is considered and, from the preliminary monitoring measurements, the major routes of exposure of the population are identified and quantified. For the most part exposures in the UK are within variations in levels of natural background radiation to be found in Europe. An exception is the dose likely to have been received by the thyroids of young people in the north of the UK. From reported measurements of I-131 in milk it is predicted that thyroid doses up to 10–20 times the annual doses received from ‘normal’ natural background radiation might have affected young children drinking fresh cows' milk. The ways in which this component of exposure could have been reduced and the criteria that govern decisions as to whether or not to implement countermeasures are discussed.

The importance of I-131 in milk as a route of exposure of the population to radioactivity is a feature that the Chernobyl accident has in common with the Windscale accident in the UK in 1957, and underlines the importance of milk-producing regions in relation to reactor-siting policy.     

Dispersal,deposition and collective doses after the Chernobyl disaster

Abstract

This article discusses the dispersal, deposition and collective doses of the radioactive fallout from the Chernobyl accident. It explains that, although Belarus, Ukraine and Russia were heavily contaminated by the Chernobyl fallout, more than half of the fallout was deposited outside these countries, particularly in Western Europe. Indeed, about 40 per cent of the surface area of Europe was contaminated. Collective doses are predicted to result in 30,000 to 60,000 excess cancer deaths throughout the northern hemisphere, mostly in western Europe. The article also estimates that the caesium-137 source term was about a third higher than official figures.     

Radioimmunotherapy with 131I-Rituximab in a Patient with Diffuse Large B-Cell Lymphoma Relapsed After Treatment with 90Y-Ibritumomab Tiuxetan

We report a case that demonstrates the efficacy of radioimmunotherapy (RIT) with radioiodinated rituximab (¹³¹I-rituximab) for relapsed diffuse large B-cell lymphoma (DLBCL). A 79-year-old male patient with DLBCL initially achieved a complete response (CR) after six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. However, the lymphoma relapsed 20 months later. Although the patient had achieved a second and a third CR after two cycles of ⁹⁰Y-ibritumomab tiuxetan, he experienced a third relapse approximately 3 years later. Between March and June 2011, the patient received three cycles of ¹³¹I-rituximab. Although he had achieved partial response after the second cycle, the disease progressed after the third cycle, and the total progression–free survival was thus 5 months. The patient suffered only relatively mild toxicity (grade 1 thrombocytopenia) during treatment. RIT with ¹³¹I-rituximab is therefore potentially effective in patients with relapsed DLBCL, even after the failure of ⁹⁰Y-ibritumomab tiuxetan therapy.     

内消瘰疬丸联合碘131治疗自主功能性甲状腺结节的疗效观察

目的 探讨内消瘰疬丸联合碘¹³¹治疗自主功能性甲状腺结节的临床疗效。方法 选取2017年2月—2019年2月在驻马店市中心医院治疗的自主功能性甲状腺结节患者86例,采用随机数字表法分为对照组与治疗组（各43例）。对照组口服碘[¹³¹I]化钠口服溶液,555 MBq/次,1次/d。治疗组患者在给予服用碘[¹³¹I]化钠口服溶液同时口服内消瘰疬丸,1次8丸,3次/d。治疗4周对比效果。观察两组患者临床疗效,同时比较治疗前后两组患者甲状腺功能指标及甲状腺结节数目和大小。结果 经治疗,治疗组有效率为97.67%,明显高于对照组（81.40%,P<0.05）。经治疗,2组三碘甲状腺原氨酸（T3）、甲状腺素（T4）、游离三碘甲状腺原氨酸（FT3）及游离甲状腺激素（FT4）水平均降低,而促甲状腺激素（TSH）水平均增高,且以治疗组改善显著（P<0.05）。经治疗,治疗组在甲状腺结节缩小及消失数目上均优于对照组（P<0.05）。结论 内消瘰疬丸联合碘¹³¹治疗自主功能性甲状腺结节可促进甲状腺结节的消失,改善机体甲状腺功能,具有一定的临床推广应用价值。     

个体化131I剂量治疗Graves病并发症的疗效分析

目的探讨个体化131I剂量治疗Graves病相关并发症的疗效。方法回顾性分析431例131I治疗的Graves病患者临床随访资料,其中合并甲亢性突眼177例,甲亢性心脏病35例,甲亢性肝功能损害82例及周期性麻痹9例。给予甲状腺组织（7．26±3．68）MBq／g的个体化131I剂量治疗,随访1年。结果131I治疗后1年,177例甲亢性突眼患者中,67例治愈（37．85％）,56例好转（31．64％）,48例无效（27．12％）,6例加重（3．39％）;35例甲亢性心脏病患者中,27例治愈（77．14％）,8例好转（22．86％）;82例甲亢性肝功能损害患者中,69例治愈（84．15％）,13例好转（15．85％）;9例周期性麻痹患者中,8例治愈（88．89％）,1例好转（11．11％）。结论131I对Graves病并发症的治疗安全、有效。