Modelling Germline Mosaicism and Different New Mutation Rates Simultaneously for Appropriate Risk Calculations in Families with Duchenne Muscular Dystrophy

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.     

Psychiatric patients and their response to experimental stress

Serum levels of Epinephrine (E), norepinephrine (NE), heart rate (HR), skin conductance reaction (SCR) and skin conductance level (SCL) were measured in schizophrenic, endogenous depressed and anxiety patients as well as in normal controls. Conditions were rest, noise and a mental arithmetic (MA) task. Schizophrenic and depressed patients had an attenuated HR response to MA. Moreover, Schizophrenic patients also had higher NE base level and the highest NE secretion during noise. Anxiety and depressed patients showed significantly lower phasic electrodermal activity (SCR) throughout the whole trial, exclusively anxiety patients had significantly higher tonic electrodermal activity (SCL). These findings indicate that autonomous reactions discriminate between patient groups and controls as well as between each other.     

第一产程胎心监护异常226例的相关因素分析

目的探讨第一产程胎心监护异常的相关因素，提示处理措施。方法2004年1月1日。12月31日对我院226例第一产程胎心监护异常的相关因素进行回顾性分析。结果第一产程胎心监护异常为综合因素所致，胎儿高危因素为91.59％，母体高危因素为65．49％，产程处理因素为42．92％。结论第一产程胎心监护异常主要与胎儿因素、母体因素有关，提高产前检查质量、加强产程监护、正确选择分娩方式极为重要。     

玉溪市2004年女职工普查结果分析

目的：为了解女职工患妇女病现状，充分认识普查普治必要性。方法：对玉溪市部分女职工进行常规妇科检查、白带多项快染、宫颈荧光筛查、乳腺红外线扫描。结果：女职工患病率74．54％，阴道炎患病率18．67％，宫颈糜烂患病率21，04％，子宫肌瘤占受检人数10．79％，慢性输卵管炎占9．60％，卵巢囊肿占4．3％，乳腺小叶增生患病率为26．86％，乳腺纤维瘤占0．43％，IF荧光宫颈癌筛查3-4分占8．33％。结论：女职工患病率高，提高宣传力度，定期开展妇女病普查普治尤为必要。     

自制无针粉末注射给药系统药物导入率的体外评价

目的 建立体外吸收评价方法，考察自制无针粉末注射给药系统的给药性能。方法 以人体皮肤为研究材料，荧光素钠作为模型药物，高效液相-荧光法检测，以透皮吸收率为指标，采用正交试验设计优选无针粉末注射的载药喷射参数。结果 建立的方法分析时间小于3min，在0．2304-9．216ng范围内呈线性关系，绝对回收率大于99．8％，RSD〈0．8％；自制无针粉末注射给药系统的最高透皮吸收率可达到40％，超过普通透皮途经400倍以上，与国外同类产品的药物导入效率（33％）相当；正交试验分析表明气源压力、喷管型号、药物剂量、药粉粒径均对无针粉末注射的效果有影响。结论 建立的研究方法简便、快速、准确、可靠，可用于无针粉末注射系统的体外研究；自制无针粉末注射给药系统的药物导入效率较高，值得进一步推广应用。     

稳定性核素测定大鼠小肠蛋白质合成

目的：建立稳定性核素（[L-^15N]亮氨酸）测定大鼠小肠蛋白质合成率的方法。方法：分别测定静脉注射相同剂量[L-^15N]亮氨酸不同时相的大鼠小肠^15N丰度及不同剂量[L-^15N]亮氨酸同一时相的大鼠小肠^15N丰度。结果：大鼠小肠游离氨基酸池中^15N核素丰度在注射后0．5h内呈线性上升并达高峰，维持4h后缓慢下降，小肠蛋白质中的^15N丰度0．5h至12h基本维持不变；随着注射剂量的增加，大鼠小肠蛋白质分数合成率（FSR）亦增加，当[L-^15N]亮氨酸剂量在1．0mmol／kg以上，FSR并不随施加[L15N]亮氨酸剂量的加大而增加。结论：在进行大鼠小肠蛋白质合成率测定时，一次性静脉注射的测量最佳时限为0．5h，剂量为1．0mmol／kg。     

Performance and comparison of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease formulae in estimating glomerular filtration rate in a Chinese Type 2 diabetic population.

AIMS: Our aim was to assess performances of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease (MDRD) formulae in estimating glomerular filtration rate (GFR) in Chinese diabetic populations and their association with vascular risks. METHODS: A total of 1009 patients with Type 2 diabetes were categorized into low estimated GFR groups (GFR < 60 ml/min/1.73 m(2)) and control groups by the two equations. The performances of these formulae were assessed at different stages of kidney function. Carotid artery intima-media thickness (IMT) and the prevalence of diabetic retinopathy or albuminuria were compared among the groups. The ability of these formulae to identify established vascular risk markers using sensitivity, specificity, positive and negative predictive values were also compared. RESULTS: The prevalence of low estimated GFR was 32.7% with the Cockcroft-Gault formula and 5.2% with the MDRD formula, respectively. In low estimated GFR subjects by the MDRD formula, IMT was significantly thicker than those by the Cockcroft-Gault formula (1.2 mm vs. 1.0 mm; P < 0.05), with a higher prevalence of albuminuria (78.4 vs. 52.8%, P < 0.05) and diabetic retinopathy (46.5 vs. 30.5%; P < 0.05). The Cockcroft-Gault formula gave a specificity of 71.7% and a sensitivity of 37.0%, and the MDRD formula gave a specificity of 96.6% and a sensitivity of 7.9% in estimating low GFR relevant for established vascular risks. CONCLUSIONS: These formulae performed differently in Chinese diabetic populations. The simplified MDRD formula is minimally superior to the Cockcroft-Gault formula for its high specificity and positive predictive values in estimating low GFR relevant for vascular risks.     

Investigation of the Effect of Neoadjuvant Chemotherapy on Stage Ⅱ Breast Cancer

OBJECTIVE To investigate the effect of neoadjuvant chemotherapy in treatment of Stage Ⅱ breast cancer. METHODS The data from 113 patients with breast cancer of the same pathologic type in Stage Ⅱ,during the period of 1995 to 2001,were analyzed retrospectively.Among the patients,47 were treated with neoadjuvant chemotherapy,and 66 received no adjuvant therapy before surgery（control group）.After the patients of the neoadjuvant chemotherapy group had received 2 courses of chemotherapy with the CMF regimen,the surgical procedure was conducted. RESULTS Complete remission（CR）was attained in 9 of the 47 cases receiving neoadjuvant chemotherapy and partial remission（PR）was reached for 22 cases.The rate of breast-conserving surgery was enhanced from 22.73%to 46.81%（P〈0.05）in the neoadjuvant treatment group. There was no difference in the 5-year overall survival（OS）and disease-free survival（DFS）rate between the two groups（P〉0.05）,but the 5-year OS and DFS of the cases with clinical tumor remission was higher compared to the control group（P〈0.05）. CONCLUSION Neoadjuvant chemotherapy can enhance the rate of breast conservation for Stage Ⅱ breast cancer and may improve the prognosis of the cases with clinical remission.     

甘肃棘豆生物碱部位体内抗肿瘤作用及对免疫功能的影响

目的 研究甘肃棘豆生物碱部位对KM小鼠肝癌H22细胞抑制作用及其对KM小鼠免疫功能的影响。 方法 采用鼠源性肝癌细胞H22移植瘤法,将60只KM小鼠随机分为5组，其中高、中、低剂量组分别给予甘肃棘豆生物碱部位32、16、8 mg/kg体重灌胃，阴性对照组给予生理盐水（NS）20 mL/kg灌胃，5- 氟脲嘧啶（5-FU）组给予5-FU 15 mg/kg体重腹腔注射，每天1次，连续给药10天。检测平均瘤重和抑瘤率,计算脾指数、胸腺指数，MTT法测脾细胞增殖率。 结果 甘肃棘豆生物碱部位高、中、低剂量组对肝癌细胞H22实体移植瘤的抑制率分别为43%、29%、23%；各剂量组小鼠的脾指数和胸腺指数均明显高于阴性对照组，中、高剂量组明显高于5-FU 组（P＜0.05）；各剂量组在24、48、72 h的脾细胞增殖率也明显高于阴性对照组及5-FU 组（P＜0.01）。 结论 甘肃棘豆生物碱部位对KM小鼠肝癌H22移植瘤有抑制作用，并能增强KM小鼠免疫功能。