Genetics of Lesch's typology of alcoholism

It is widely accepted that dopamine and serotonin (5-HT) neurotransmission can be critically involved in the development of alcohol abuse and alcohol dependence. Lesch's typology of alcoholism has been gaining increasing popularity as it qualitatively differentiates patients into different treatment response subgroups. The aim of the present study was to evaluate a possible genetic background of Lesch's typology with special emphasis placed on dopamine- and serotonin-related genes. 122 alcoholics (the mean age: 35+/-9 years) were investigated. According to Lesch's typology, 58 patients were of type I, 36 patients of type II, 11 patients of type III, and 17 patients of type IV. Alcohol drinking and family history was assessed by means of a structured interview, based on the Semi-Structured Assessment for the Genetics of Alcoholism. 150 control subjects without psychiatric disorders were also recruited. The control group was ethnically-, age- and gender-matched to the patients. The DRD2 TaqIA, exon 8, and promoter -141C ins/del polymorphisms as well as COMT Val158Met, 5HTT 44 bp del in promoter, and DAT 40 bp VNTR polymorphisms were detected by means of PCR. No significant differences were observed when the whole group of alcoholics and the controls were compared. Similarly, there were no differences between either the Lesch type I or type II alcoholics and the control subjects. No significant differences were observed between type I and type II alcoholics. Alleles frequencies were not calculated for the Lesch type III and type IV alcoholics since the number of patients was too small. The present results argue against any major role of the investigated polymorphisms in either Lesch type I or type II alcoholism. More comprehensive studies are needed to define the role of the investigated polymorphisms in Lesch type III and type IV alcoholism.     

Accuracy and inter-observer variation in the classification of dysarthria from speech recordings

Background   Dysarthria may be classified as flaccid, spastic, ataxic, hypokinetic, choreatic, dystonic, or mixed. We hypothesized that in routine neurological practice the reliability and accuracy of perceptual analysis alone in the classification of dysarthria is low and that this classification is mainly based on the clinical context rather than on the perception of speech. We therefore studied the accuracy and the inter- observer agreement in the classification of dysarthrias on the basis of perceptual analysis alone. Methods   Seventy two neurologists and neurological trainees classified recorded speech samples of 100 patients as flaccid, spastic, ataxic, extrapyramidal, or mixed dysarthria, or as not dysarthric. All observers were blinded to the patients’ final diagnosis, which was based on all clinical features and investigations. In the analysis the observers were arranged in eight groups of nine observers, or four paired groups with similar levels of clinical experience. Together, the observers in a given group rated all 100 recordings. Results   The accuracy of the classification was poor (35 % were classified correctly) and the inter-observer agreement between paired groups low (κ 0.16 to 0.32). The level of experience in neurology did not have a significant influence. Conclusion   Neurological trainees as well as experienced neurologists have great difficulty in identifying specific types of dysarthria on the basis of perceptual analysis alone. In clinical practice this probably means that most neurologists will classify dysarthria in the context of other features from neurological examination or ancillary investigations.     

Compelling or irrelevant? Using number needed to treat can help decide

Objective: The metric of number needed to treat (NNT), defined as the number of patients who need to be treated to achieve one additional favorable outcome, can help clinicians appraise claims that one intervention is meaningfully superior to the other. Method: A review of the use of NNT to evaluate the differences between interventions in the treatment of depression, schizophrenia and bipolar disorder. Instead of using disparate measures such as point change on a rating scale, kilograms gained over time or relative differences, results can be converted into a common unit of measure –‘patient units’– so that the clinician can anticipate how often actual differences between interventions would be expected to be observed. Calculation of NNT is demonstrated using reports published in the psychiatric literature, together with different graphical techniques to display this. Results: Clinical trial results expressed as NNT can be easily summarized and communicated effectively to patients, their families and payers. Limitations include ensuring that the NNT metric is calculated from well‐designed and well‐conducted research that enrolls subjects similar to patients that one treats in actual clinical practice, with doses of medications similar to what is used in the ‘real world’. Direct calculation of NNT is limited to binary or dichotomous outcomes. Conclusion: Using NNT can help predict treatment response in terms of both efficacy and tolerability.     

DNA interactions of new cytotoxic tetrafunctional dinuclear platinum complex trans,trans-[{PtCl2(NH3)}2(piperazine)

A new tetrafunctional dinuclear platinum complex trans,trans-[{PtCl2(NH3)}2(piperazine)] with sterically rigid linking group was designed, synthesized and characterized. In this novel molecule, the DNA-binding features of two classes of the platinum compounds with proven antitumor activity are combined, namely trans oriented bifunctional mononuclear platinum complexes with a heterocyclic ligand and polynuclear platinum complexes. DNA-binding mode of this new complex was analyzed by various methods of molecular biology and biophysics. The complex coordinates DNA in a unique way and interstrand and intrastrand cross-links are the predominant lesions formed in DNA in cell-free media and in absence of proteins. An intriguing aspect of trans,trans-[{PtCl2(NH3)}2(piperazine)] is that, using a semi-rigid linker, interstrand cross-linking is diminished relative to other dinuclear platinum complexes with flexible linking groups and lesions that span several base pairs, such as tri- and tetrafunctional adducts, become unlikely. In addition, in contrast to the inability of trans,trans-[{PtCl2(NH3)}2(piperazine)] to cross-link two DNA duplexes, the results of the present work convincingly demonstrate that this dinuclear platinum complex forms specific DNA lesions which can efficiently cross-link proteins to DNA. The results substantiate the view that trans,trans-[{PtCl2(NH3)}2(piperazine)] or its analogues could be used as a tool for studies of DNA properties and their interactions or as a potential antitumor agent. The latter view is also corroborated by the observation that trans,trans-[{PtCl2(NH3)}2(piperazine)] is a more effective cytotoxic agent than cisplatin against human tumor ovarian cell lines.     

Validation of pulse contour derived stroke volume variation during modifications of cardiac afterload

Background: Left ventricular stroke volume variation (SVV) or its surrogatesare useful tools to assess fluid responsiveness in mechanicallyventilated patients. So far it is unknown, how changes in cardiacafterload affect SVV. Therefore, this study compared left ventricularSVV derived by pulse contour analysis with SVV measured usingan ultrasonic flow probe and investigated the influence of cardiacafterload on left ventricular SVV. Methods: In 13 anaesthetized, mechanically ventilated pigs [31(SD 6)kg], we compared cardiac output (CO), stroke volume (SV), andSVV determined by pulse contour analysis and by an ultrasonicaortic flow signal (Bland–Altman analysis). After obtainingbaseline measurements, cardiac afterload was increased usingphenylephrine and decreased using adenosine (both continuouslyadministered). Measurements were performed with a constant tidalvolume (12 ml kg^–1) without PEEP. Results: Neither increasing mean arterial pressure (MAP) [from 59 (7)to 116 (19)] nor decreasing MAP [from 63 (7) to 39 (4)] affectedCO, SV, and SVV (both methods). Method comparison revealed abias for SVV of 0.1% [standard error of the mean (SE) 0.8] atbaseline, –1.2% (SE 0.8) during decreased and 4.0% (SE0.7) during increased afterload, the latter being significantlydifferent from the others (P < 0.05). Thereby, pulse contouranalysis tended to underestimate SVV during decreased afterloadand to overestimate SVV during increased afterload. Limits ofagreement were approximately 6% for all points of measurement. Conclusions: Left ventricular SVV is not affected by changes in cardiac afterload.There is a good agreement of pulse contour with flow derivedSVV. The agreement decreases, if afterload is extensively augmented.     

血压变异性的临床研究进展

人体正常血压在生理机制调解下呈现规律的波动变化。近年来国际上许多大型研究表明血压异常波动、血压变异性增大可促进心脏、脑、肾脏等重要靶器官受损,具有重要的临床意义。现就血压变异性的近期研究进展及相关药物治疗做一综述。     

Structural uniformity of neocortex,revisited

The number of neurons under a square millimeter of cortical surface has been reported to be the same across five cortical areas and five species [Rockel et al. (1980) Brain 103(2):221–244] despite differences in cortical thickness between the areas. Although the accuracy of this result has been the subject of sharp debate since its publication approximately 30 y ago, the experiments of Rockel et al. have never been directly replicated with modern stereological methods. We have replicated these experiments and confirm the accuracy of the original report. In addition, we have observed that the number of glial cells under a square millimeter of cortical surface depends on cortical thickness, but not on cortical area or species.     

Dietary coral calcium and zeolite protects bone in a mouse model for postmenopausal bone loss

In patients diagnosed with osteoporosis, calcium is lost from bones making them weaker and easily susceptible to fractures. Supplementation of calcium is highly recommended for such conditions. However, the source of calcium plays an important role in the amount of calcium that is assimilated into bone. We hypothesize that naturally occurring coral calcium and zeolite may prevent ovariectomy-induced bone loss. We have measured bone loss in ovariectomized mice supplemented with coral calcium and Zeolite. Female C57BL/6 mice were either sham-operated or ovariectomized and fed diets containing coral calcium or zeolite for 6 months. Serum was analyzed for bone biochemical markers and cytokines. Bones were analyzed using dual x-ray absorbtiometry, peripheral quantitative computed tomography, and micro–computed tomography densitometry. In the distal femoral metaphysis, total bone and cortical bone mass was restored and the endocortical surface was significantly decreased in coral calcium and zeolite fed ovariectomized (OVX) mice. Trabecular number and the ratio of bone volume to total volume was higher in OVX mice after coral calcium and zeolite feeding, while trabecular separation decreased in the different treatment OVX groups. Coral calcium protected bone to a lesser extent in the proximal tibia and lumbar vertebrae. Overall, coral calcium and zeolite may protect postmenopausal bone loss.     

用圆形分布法探讨疫苗干预对麻疹发病季节性的影响

[目的]探讨麻疹流行的季节性规律及麻疹疫苗的干预对其流行高峰期的影响.[方法]采用圆形分布法.分析湖南省1951～1999年麻疹发病高峰日的变迁情况并对疫苗干预的不同时期的流行高峰日进行比较.[结果]从1951至1999年,划分的各个时期均存在麻疹发病高峰期,高峰日逐阶段后移达两个月江结论]疫苗干预可使麻疹发病高峰日后移,但不改变每年出现发病高峰季节的流行规律;圆形分布分析单峰型有周期性的疾病季节高峰特征,具有计算简单、描述直观的优点.     

凝血酶原基因G20210A变异在血栓栓塞症中的研究

目的 研究凝血酶原基因G20210A变异在血栓栓塞症的发病情况。方法 30例深静脉血栓形成患者、32例脑血栓患者和40名健康献血者进行聚合酶链反应然后进行限制性内切酶Hind Ⅲ酶切、琼脂糖凝胶电泳分析。结果 患者和健康献血者的琼脂糖凝胶电泳结果均显著正常带型，即345bp一条带。结论 凝血酶原基因G20210A变异在我国的发生率很低，很可能象FV Leiden变异引起的活化蛋白C抵抗一样存在着明显的种族差异。