166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy.

166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation.     

变温培养对泰乐菌素发酵的影响

在泰乐菌素发酵过程中的不同阶段采用不同的培养温度,通过实验考察其对泰乐菌素发酵的影响。实验结果表明,变温培养的发酵水平要高于其它恒温培养的发酵水平。     

4110例肝炎分型分析

[目的]探讨各型肝炎的感染率。[方法]研究对象为我院住院及门诊患者，共计4110例。采用微粒子酶免分析法（MEIA）及酶联免疫吸附法（ELISA）进行肝炎分型（甲、乙、丙、丁、戊、庚肝）检测。[结果]4110例受检者中，单纯乙肝感染者133例，占3．24％；单纯丙肝感染者134例，占3．26％；单纯戊肝感染者2例，占0．05％；乙肝合并丙肝感染者3例，占0．07％；丙肝合并戊肝感染者1例，占0．02％；HAV、HDV、HGV无一例感染，感染率为0。另外，男性受检者2088人，乙肝感染者88人，占4．21％；丙肝感染者48人，占2．30％；女性受检者2022人，乙肝感染45人，占2．23％；丙肝感染86人，占4．25％。[结论]除丙肝外，各型感染率均低于全国平均感染率，与相关资料报道相差甚远。乙肝及丙肝仍以单纯感染多见。另，本组资料还显示，男性较女性更易感染乙肝病毒，而女性感染丙肝者远远高于男性，对于丙肝感染的性别差异，尚无报道，需进一步探讨。     

PINK1 mutations in sporadic early-onset Parkinson's disease.

Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.     

含左氧氟沙星及卷曲霉素方案治疗耐多药肺结核近期疗效分析

目的　观察和评价含左氧氟沙星和卷曲霉素联合化疗方案在耐多药肺结核 (MDR PTB)治疗中的疗效。方法　将 177例MDR PTB患者分为治疗组 88例和对照组 89例。化疗方案 :治疗组以左氧氟沙星和卷曲霉素为主 ,联合利福喷汀、异烟肼、对氨基水杨酸钠、吡嗪酰胺 ;对照组用链霉素、乙胺丁醇 ,联用药物同治疗组 ,疗程均为 2 1个月。结果　共有 16 1例患者完成化疗疗程 ,治疗组 82例 ,痰菌阴转率 83% ;对照组 79例 ,痰菌阴转率 5 8% ;痰菌阴转率治疗组明显高于对照组 (P <0 0 1) ;治疗组病灶显效率 5 0 % ,空洞闭合率 6 3% ,治疗组优于对照组 (P <0 0 1) ;治疗组的药物不良反应率为 31% ,对照组为 35 % ,两组比较差异无显著性 (P >0 0 5 )。结论　含左氧氟沙星和卷曲霉素的方案治疗MDR PTB ,有助于痰菌阴转和病变吸收好转 ,药物不良反应低 ,值得在临床上推广应用     

中草药灌肠液＋西医药治疗慢性结肠炎66例体会

目的 探讨中西医结合治疗慢性结肠炎的体会。方法 对采用中草药灌肠液E＋西医药治疗66例慢性结肠炎的临床观察进行分析。结果66例患者中，有效率达96％左右。结论 慢性结肠炎是我国的常见病及多发病，采用中草药＋西医药治疗，效果好，药价低廉，操作简便，值得推广，应予重视。     

bevacizumab治疗乳腺癌的基础和临床研究

分子靶向药物bevacizumab是针对血管内皮生长因子(VEGF)的重组人源化单克隆抗体,在多种恶性肿瘤的治疗中显示了临床效果。现就bevacizumab的作用机制及其在乳腺癌治疗中的临床研究进展作一综述。