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.     

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。     

氧化砷对小鼠腹水型肝癌细胞的作用

目的 :研究氧化砷对移植性腹水型肝癌细胞的抗癌作用。方法 :肝癌细胞 (1 8× 10 7)接种入小鼠腹腔。对照组注射NS(0 8mL) ,余组用氧化砷 (1,2 ,3μmol/L)腹腔注射 ,每日 1次 ,共 10日。结果 :第 10天腹水细胞计数 ,1,2和 3μmol/L组瘤细胞锐减 (P <0 0 5 ) ,但第 16天腹水肿瘤细胞急骤增加。结论 :氧化砷对腹水肿瘤细胞有暂时抑制作用。     

庆大霉素对豚鼠前庭上皮IGF-1及其受体表达的影响

目的：研究庆大霉素对豚鼠前庭上皮胰岛素样生长因子-1（insulin-like growth factor-1，IGF-1）及其受体（insulin-like growth factor-1 receptor，EGF-1R）表达的影响，并探讨其生物学特性。方法：采用免疫组织细胞化学方法，以抗IGF-1及IGF-1R抗体为标记物，检测庆大霉素损伤后豚鼠前庭上皮自发修复期IGF-1及IGF-1R的表达变化和分布特点；采用Brdu体内标记和抗Brdu抗体免疫组化染色，检测庆大霉素损伤后豚鼠前庭上皮增殖的变化。结果：IGF-1及IGF-1R在正常成年豚鼠前庭上皮细胞中有低水平表达，庆大霉素损伤后，其表达增多。在1d组IGF-1及IGF-1R表达最强，其后逐渐减少。在正常对照组中无Brdu阳性细胞。各实验组均观察到Brdu阳性细胞，7d组最多。结论：庆大霉素损伤后，豚鼠前庭上皮IGF-1及IGF-1R表达增强，其时程变化与细胞增殖活动密切相关。IGF-1在豚鼠前庭上皮损伤后的细胞增殖中可能起重要信号转导作用。     

来源于骨髓和脐带血的基质细胞基本特性的比较

目的比较骨髓与脐带血细胞体外培养基质细胞的基本特性,为基质细胞的选择应用提供依据.方法用Dexter长期培养体系培养骨髓和脐带血基质细胞,以细胞增殖、细胞形态、细胞化学染色、细胞表面及基质细胞支持另一骨髓细胞形成的鹅卵石造血区(CAFC),长期培养起始细胞(LTC-IC)为指标,比较两者的生长特性、成分及功能.结果①细胞生长特性:出现贴壁细胞时间,骨髓细胞为培养3d,脐带血细胞为培养5～6d;细胞融合成片时间,骨髓细胞为培养10～14d,脐带血细胞为培养12～18d;第21天细胞增殖数,骨髓比脐带血细胞增殖少;②细胞成分:21d培养后细胞成分,骨髓来源者以成纤维细胞为主,其次是巨噬细胞与内皮细胞,脂肪细胞最少;脐带血细胞来源者,以巨噬细胞为主,其次是内皮细胞、成纤维细胞,偶见脂肪细胞;细胞化学与上述结果基本一致;细胞表面抗原检测,CD14、CD45的表达骨髓细胞明显低于脐带血细胞;③细胞功能:骨髓来源的基质细胞较脐带血细胞的基质细胞支持另一骨髓细胞形成的CAFC和LTC-IC明显多.结论①生长特征:形成贴壁细胞时间骨髓较脐带血短,骨髓细胞比脐带血细胞有核细胞数增殖快、持续时间相对短;②细胞成分特性:骨髓来源形成的基质细胞以成纤维细胞为主,脐带血来源者以巨噬细胞为主;③细胞功能特性:骨髓细胞形成的贴壁细胞较脐带血细胞形成的贴壁细胞更利于CAFC、LTC-IC生长.