A model for the determination of carbamazepine clearance in children on mono- and polytherapy

Objective: To derive a model describing carbamazepine (CBZ) clearance in children, in terms of individual patient characteristics. Methods: One hundred and eighteen steady-state serum carbamazepine concentration measurements were gathered during normal routine care of 72 compliant out-patients (2.3–16.3 years old). Levels were obtained from patients receiving monotherapy (55%), concomitant valproate (26%), or concomitant inducers (phenytoin, phenobarbitone; 19%). A one-compartment model was used to fit the data with the computer programme Nonlinear Mixed Effects Model (NONMEM). Results: Weight, age and concomitant medication were all important determinants of clearance. The final model for clearance (l · h⁻¹) was: CL = [0.7(WT)^0.4] · M, where WT is patient weight (kg) and M is a scaling factor for concomitant medication, with a value of 1 for patients on CBZ monotherapy or concomitant valproate and 1.4 for those receiving concomitant inducers. For the purposes of this analysis, bioavailability (f) was assumed to be complete, i.e., f is thus included in the term CL. Conclusions: CBZ clearance decreased with increasing age. As age and weight were correlated, either variable was a satisfactory predictor. The influence of both the inducers and valproate on CBZ clearance was as expected. This model, which describes clearance in terms of patient-specific details, can be used when predicting the maintenance dose required to achieve a target mean steady-state CBZ concentration in children. Received: 10 May 1997 / Accepted: 16 February 1998     

A concordance of nucleotide substitutions in the first and second hypervariable segments of the human mtDNA control region

A new and easily accessible concordance of nucleotide substitutions in the hypervariable segments of the human mitochondrial DNA (mtDNA) control region has been constructed. The concordance indexes all population-specific mtDNA sequences in a standardized format. The first edition of the concordance includes 1,440 sequences representing 762 mtDNA types from over 65 populations for hypervariable region 1, and 520 sequences representing 260 mtDNA types from over 26 populations for hypervariable region 2. Investigators are invited to submit new sequences to the database, and details for doing so are given in the text.     

用于杀虫剂评价的水池中无脊椎动物的群落结构及其种群动态

实验水池是评价杀虫剂效应和安全生的重要场所，水池中无脊椎动物群落结构和种群动态是评价杀虫剂的基础资料和考核指标，本文报告１９９２年至１９９３年在美国佛罗里达中部地区对应用于杀虫剂评价的实验水池中昆虫与其它无脊椎动物群落结构及其优势种的种群动态研究结果，用羽化诱捕、勺舀、网拉及挖取底物法，从实验水池中共采到昆虫与其它无脊椎动物５０余类，其中，羽化诱捕到的昆虫中摇蚊占９３．９％，蜉蝣目昆虫占４．６％，     

Phylogenetic analysis of mtDNA haplogroup TJ in a Finnish population

An association between mitochondrial DNA (mtDNA) mutations 11778G>A and 14484T>C and mtDNA haplogroup J suggests that this haplogroup harbors substitutions capable of modifying the phenotype of Leber's disease. Our knowledge of the compilation of substitutions in haplogroup J is based on only a small number of complete mtDNA sequences, however. We constructed phylogenetic networks for mtDNA haplogroup TJ that were based on the sequence of the complete coding region and the hypervariable segment I, respectively, in 28 Finnish samples. The networks revealed a subdivision of the haplogroup into subclusters T1, T2, J1, and J2, while comparison of the two networks suggested nine fast evolving nucleotide sites in the hypervariable segment I. Genotypes of patients harboring 11778G>A or 14484T>C were obtained from the literature and were then placed in the network. Only four substitutions were found to be common to the patients, but none of these was unique to haplogroup J. If increased penetrance of the 11778G>A and 14484T>C mutations in patients belonging to haplogroup J is assumed, combinations of ancient substitutions must be implicated. Received: September 29, 2000 / Accepted: November 10, 2000     

Climacteric symptoms in an unselected sample of Swedish women

A questionnaire on climacteric symptoms was sent to every woman living in the city of Linköping, Sweden (120,000 inhabitants) who was born in 1928 or 1930. Of the 1246 women concerned, 1118 (90%) responded. At the time of the survey, 252 women (23%) were pre-menopausal. In the total sample, 10B had undergone hysterectomy and/or bilateral oophorectomy. The median age at natural menopause was 51 yr.

Climacteric symptoms were reported by 75% of the women, the predominating complaints being sweating attacks and hot flushes. Vaginal dryness and tenderness were experienced by 30% of the post-menopausal women, the discomfort tending to become more common as the duration of the post-menopausal period lengthened.

After the menopause, every third woman experienced periods of depression more often than previously. Depression was positively correlated to the severity of the vasomotor symptoms.

Fifty percent of the women expressed interest in receiving oestrogen treatment, although only 7% were using oestrogens at the time of the survey. This discrepancy is probably due to widespread apprehension in Swedish society - shared by the doctors - in regard to ‘hormonal treatment’.     

样本量对等位基因检出数量的影响

以中国37个不同民族9个常染色体STR基因座的群体遗传研究数据资料为例，探讨群体遗传学研究中常染色体STR基因座等位基因检出数量与样本量之间的关系，即样本量对等住基因检出数量的影响。结果显示在一定范围之内，样本量的大小与所观测到的不同基因座等位基因检出数量之间存在正相关关系。当超过一定范围时，样本量的继续增加不再明显影响等位基因的检出数量。杂合度较低的位点随样本量的变化波动较大，杂合度较高的位点随样本量的变化波动较小。     

Sequential movement representations based on correlated neuronal activity

We tested the hypothesis that sequential movements are represented in the correlated activity of motor cortical neurons. We simultaneously recorded multiple single neurons in the motor cortex while monkeys performed a two-segment movement sequence. Before any movement began the correlated spike firing between pairs of neurons differed when these sequences were planned as whole (planned) as compared to when they were planned one segment at a time (unplanned) even when the firing rates of these neurons did not distinguish between the two conditions. Moreover, the correlation strength was significantly larger when the directional preferences of the neurons matched the direction of the final segment of the sequence. Our results suggest that spatially distributed groups of MI neurons form dynamic correlation structures that distinguish different forms of sequential action. Electronic Publication     

Insulin Minimal Model Indexes and Secretion: Proper Handling of Uncertainty by a Bayesian Approach

The identification of the insulin minimal model (MM) for the estimation of insulin secretion rate (ISR) and physiological indexes (e.g. beta-cell sensitivity) requires the knowledge of C-peptide (CP) kinetics. The four parameters of the two-compartment model of CP kinetics in a given individual can be derived either from an additional bolus experiment or, more frequently, from a population model. However, in both situations, the CP kinetics is uncertain and, in MM identification, it should be treated as such. This paper shows how to handle CP kinetics uncertainty by using a Bayesian methodology. In seven subjects, MM indexes and ISR were estimated together with their confidence intervals, using either the bolus data or the population model to assess CP kinetics. The two main results that arise from the application of the new methodology are: (i) the use of the population model in place of the bolus data to determine CP kinetics does not affect, on average, the point estimates of ISR profile and MM parameters but only the confidence intervals which becomes wider (less than 50%); (ii) in both the bolus and population situation neglecting the uncertainty of CP kinetics, as done in MM literature so far, introduces no bias, on average, on point estimates of MM indexes but only an underestimation of confidence intervals.     

A new haplogroup pattern displayed in Fujian Han in China

Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific polymerase chain reaction. The results indicated that the M₉G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M₁₂₂C frequency was only 22.78%, and M₄₅A and M₁₀₃T were default. The distinctive haplogroup frequencies (H₁, H₅, and H_6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type. Received: October 13, 2001 / Accepted: December 3, 2001     

东营区≥45岁人群结直肠癌初筛结果分析及肠镜顺应性调查

目的 对东营区≥45岁常住居民进行结直肠癌筛查,并探讨初筛阳性者肠镜顺应性及其影响因素,为提高居民结直肠癌筛查工作提供科学依据。方法 采用方便抽样方法选择辖区内2个镇和3个街道的社区卫生服务中心作为结直肠癌筛查志愿者招募点招募≥45岁常住居民为研究对象开展结直肠癌筛查及问卷调查,对初筛阳性者进一步进行肠镜检查,采用描述性分析方法对居民结直肠筛查结果及肠镜顺应性进行分析,并对其影响因素进行单、多因素分析。结果 本研究共纳入1 201人进行分析,男662人,女539人,45~59岁372人,60~69岁495人,70~79岁334人。初筛阳性人数总计371例,其中危险因素初筛阳性154例,FOBT阳性298例,危险因素和FOBT阳性双阳性者81例,初筛阳性率为30.89%。男性（OR=3.177）、黏液血便史（OR=7.683）以及肠道息肉病史（OR=5.008）为结直肠癌初筛阳性的危险因素。371例初筛阳性者中121例完成结肠镜检查,结肠镜检查顺应率为32.61%。性别（OR=2.776）、年龄（OR=0.511、0.433）、婚姻状况（OR=4.267）、文化程度（OR=2.782、3.916）、医疗保险（OR=2.743）是结直肠癌初筛阳性者结肠镜检查顺应性的影响因素。结论 东营市东营区结直肠癌初筛阳性率较高,应加强对存在黏液血便史以及肠道息肉病史男性个体人群的结直肠癌筛查。居民结直肠镜检查顺应性较低,尤其是60岁及以上、非在婚、文化程度较低、无医保的女性个体,可特异性强化对该群体个体的健康教育,提高其结直肠镜顺应性。