Absolute configuration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol formed metabolically from 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone (NNK). Using the chiral derivatizing agent, (R)- (+)-alpha-methylbenzyl isocyanate [(R)-(+)-MBIC], previous work has shown that the enantiomeric ratio of metabolically formed NNAL and its glucuronide derivative may be species dependent. However, the absolute configuration of such NNAL has not been previously reported. Synthetically prepared racemic NNAL was converted to diastereomeric esters by reaction with (R)-(+)- and (S)-(-)-alpha-methoxy-alpha- (trifluoromethyl)phenylacetic acid (MTPA) chloride (Mosher's reagent) and the products were characterized by 1H-NMR. Based on chemical shift data, the absolute configuration of NNAL in each diastereomeric ester was assigned. Hydrolysis of (R)-NNAL-(R)-MTPA gave (R)-NNAL. This was converted to the corresponding carbamate by reaction with (R)-(+)-alpha- MBIC and the absolute configurations of the diastereomeric carbamates formed by reaction of (R)- and (S)-NNAL with (R)-(+)-MBIC were thereby assigned. Conversion of metabolically produced NNAL to the same carbamates allowed us to assign the NNAL formed from NNK by rat liver microsomes as (R)-NNAL. The major and minor NNAL-glucuronide diastereomers found in the urine of patas monkeys and humans exposed to NNK were similarly assigned; they were formed from (R)-NNAL and (S)- NNAL, respectively.      

Early speech changes in children with multichannel cochlear implants

A number of studies have demonstrated that cochlear implants provide an improved auditory signal and enhance the development of speech-perception and production skills for profoundly deaf children. However, exactly when these early speech skills begin to develop remains unclear. To explore this issue, we observed, for a 1-year period, four prelingually deaf children who underwent implantation consecutively within 1 month of each other, and we paid particular attention to the first few months of rehabilitation. We found immediate speech scores as early as the first day of implant tune-up. Speech production continued to improve rapidly throughout the first 4 months but exhibited a generally slower rate of progress in some of the speech-production skills at 1 year. We also found vowel-production skills to be the easiest to achieve, with word-pattern recognition and consonant voicing of intermediate difficulty. Consonant placing and manner of consonant production were the hardest skills to achieve. Results of speech-perception tests 1 year after implantation were markedly improved over preimplantation levels in three of the four children. These early speech changes stress the need for maximization of the capability of the cochlear implant by institution of immediate and intensive speech rehabilitation efforts for prelingually deaf children. (Otolaryngol Head Neck Surg 1996;115:508-12.)     

加替沙星无菌检查方法的建立与标准操作探讨

目的:建立加替沙星原料及制剂无菌检查法及标准操作方法。方法:按2005年版中国药典无菌检查法验证实验的有关要求,通过接种阳性代表菌株,对薄膜过滤、添加中和剂等去除加替沙星抗菌活性的实验方法和条件进行验证,逐步建立加替沙星原料及制剂无菌检查的标准操作方法。结果:在对加替沙星不同原料及制剂样品适当的处理基础上,采用薄膜过滤法,以0.1%蛋白胨水溶液作为冲洗液,约每滤筒300 mL 的冲洗量,每筒培养基中加入0.1 mol·L~(-1)硫酸锰溶液3 mL 可去除加替沙星对细菌的抑菌作用。结论:加替沙星具有较强的抑菌活性,通过适当的样品处理、薄膜过滤法和添加硫酸锰溶液作为重金属络合剂,去除加替沙星抑菌活性,可对解决喹诺酮类抗生素无菌检查问题起到较好的参考作用。     

Participation of older newly-diagnosed cancer patients in an observational prospective pilot study: an example of recruitment and retention

Background  

There have been few prospective observational studies which recruited older newly-diagnosed cancer patients, and of these only some have reported information on the number needed to screen to recruit their study sample, and the number and reasons for refusal and drop-out. This paper reports on strategies to recruit older newly-diagnosed cancer patients prior to treatment into an observational prospective pilot study and to retain them during a six-month period.     

Prevention of recurrence and prolonged survival in primary central nervous system lymphoma (PCNSL) patients treated with adjuvant high-dose methylprednisolone

Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone (HDMP) to prevent 'trafficking' of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the 'blood brain barrier (BBB)'. Three men with newly diagnosed PCNSL, ages 62, 76 and 78y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin's lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+ months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.     

Text messaging as a new method for injury registration in sports: A methodological study in elite female football

Methodological differences in epidemiologic studies have led to significant discrepancies in injury incidences reported. The aim of this study was to evaluate text messaging as a new method for injury registration in elite female football players and to compare this method with routine medical staff registration. Twelve teams comprising 228 players prospectively recorded injuries and exposure through one competitive football season. Players reported individually by answering three text messages once a week. A designated member of the medical staff conducted concurrent registrations of injuries and exposure. Injuries and exposure were compared between medical staff registrations from nine teams and their 159 affiliated players. During the football season, a total of 232 time‐loss injuries were recorded. Of these, 62% were captured through individual registration only, 10% by the medical staff only, and 28% were reported through both methods. The incidence of training injuries was 3.7 per 1000 player hours when calculated from individual registration vs 2.2 from medical staff registration [rate ratio (RR): 1.7, 1.2–2.4]. For match injuries, the corresponding incidences were 18.6 vs 5.4 (RR: 3.4, 2.4–4.9), respectively. There was moderate agreement for severity classifications in injury cases reported by both methods (kappa correlation coefficient: 0.48, confidence interval: 0.30–0.66).     

微小染色体维持蛋白5和细胞增殖核抗原在肺癌组织中的表达及其临床意义

目的:检测MCM5蛋白和PCNA在肺癌组织中的表达,探讨两者与肺癌各临床病理因素之间的关系及两者相互的联系,从而为评估肺癌的发生发展、预后及治疗提供理论依据。方法:运用免疫组织化学技术分别检测MCM5蛋白和PCNA在68例肺癌组织和20例正常组织中的表达情况,分析其与临床病理因素之间的关系及两者相互的联系。结果:MCM5表达的阳性信号位于细胞核,胞浆无着色。在正常肺组织中,MCM5的表达局限在上皮基底部的1/3至1/2的细胞,在肺癌组织中,MCM5的表达分布广泛,靠近上皮表面的细胞也可见大量表达。(1)正常肺组织和肺癌组织的MCM5的表达的差别有统计学意义(P<0.01)。(2)肺癌中MCM5表达与分化程度、淋巴结转移有显著相关性(P<0.05),与病人年龄、性别无显著相关性(P>0.05)。(3)PCNA的表达与肺癌的分化程度无显著相关性(P>0.05)。(4)在肺正常组织中,PCNA标记指数高于MCM5标记指数,两者具有显著差异性(P<0.05)。在肺癌组织中,PCNA与MCM5标记指数无显著差异性(P>0.05)。结论:(1)在肺组织中,微小染色体维持蛋白5(MCM5)是一种可靠的细胞增殖标志物。根据MCM5染色的组织结构差异和平均光密度能比较准确区分肺正常组织和癌组织。MCM5表达与肺癌的分化程度显著相关,因此MCM5表达可以提示肺癌的恶性程度,有助于临床判断病人的预后以及选择合适的治疗方法。MCM5与其他增殖标志PCNA相比是一种更好的细胞增殖标志物,是肺癌细胞的更好标志和分级指标。(2)PCNA在肺癌组织中过表达,提示PCNA的过表达与肺癌的发生发展关系密切。     

去甲硫氨酸全肠外营养对大鼠血清氨基酸谱的影响

目的观察去甲硫氨酸全肠外营养对大鼠血清氨基酸谱等的影响.方法 Wistar大鼠24只,随机分为含甲硫氨酸(+MetTPN,n=12)和去甲硫氨酸全肠外营养2组(-MetTPN,n=12),分别给予相应的TPN支持.治疗7d后,每组随机抽取6只大鼠处死,检测血清FAA(HPLC法)、肝肾功能和全血常规,同时作心、肺、肝、肾组织病理学检查.两组其余大鼠继续原TPN治疗,观察生存期.结果 -MetTPN组大鼠血清游离Met、Cys明显降低,Asp、Glu、Ser等显著增高;大鼠体重下降;血清总蛋白和白蛋白水平下降;血常规和肾功能未见明显异常;组织学检查见肝细胞轻度肿胀,细胞核仁增粗,心肺肾未见明显异常;平均生存18d.对照组上述检查未见异常,除一只大鼠因导管并发症于TPN第16d死亡,其余大鼠全部存活.结论 -MetTPN一周可致大鼠血清游离Met、Cys明显降低和Asp、Glu、Ser等显著增高,及轻度肝功能改变;随着-MetTPN时间延长,出现严重的代谢紊乱和器官功能障碍导致死亡.     

Radiation dose reduction during hysterosalpingography: an application of scanning-beam digital radiography

Hysterosalpingography was performed in 31 patients by means of a low-dose scanning-beam digital radiographic system. The technique permits adequate evaluation of gynecologic abnormalities while allowing significant reduction in radiation: 2.4-mR (6.1 X 10(-7) C/kg) exposure to the skin and 0.7-mrad (7 X 10(-6) Gy) mean dose to the ovaries per image obtained. Sixteen patients demonstrated readily recognizable and documented abnormalities, corroborated by laparoscopy, laparotomy, or other supportive evidence.