Association analysis of genes in the renin‐angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart Study

Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin‐angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima‐media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population.     

Physical inactivity, excess adiposity and premature mortality

The purpose of this report is to review the evidence that physical inactivity and excess adiposity are related to an increased risk of all‐cause mortality, and to better identify the independent contributions of each to all‐cause mortality rates. A variance‐based method of meta‐analysis was used to summarize the relationships from available studies. The summary relative risk of all‐cause mortality for physical activity from the 55 analyses (31 studies) that included an index of adiposity as a covariate was 0.80 [95% confidence interval (CI) 0.78–0.82], whereas it was 0.82 [95% CI 0.80–0.84] for the 44 analyses (26 studies) that did not include an index of adiposity. Thus, physically active individuals have a lower risk of mortality by comparison to physically inactive peers, independent of level of adiposity. The summary relative risk of all‐cause mortality for an elevated body mass index (BMI) from the 25 analyses (13 studies) that included physical activity as a covariate was 1.23 [95% CI 1.18–1.29], and it was 1.24 [95% CI 1.21–1.28] for the 81 analyses (36 studies) that did not include physical activity as a covariate. Studies that used a measure of adiposity other than the BMI show similar relationships with mortality, and stratified analyses indicate that both physical inactivity and adiposity are important determinants of mortality risk.     

老年人前瞻性记忆损害的研究

目的 了解健康老年人前瞻性记忆改变的情况,初步探讨老年人基于事件的前瞻性记忆(EBPM)和基于时间的前瞻性记忆(TBPM)损害程度的区别.方法 建立前瞻性记忆的神经心理学测验方法,测试教育程度相匹配的40名健康老年人和40名健康成年人的EBPM和TBPM.结果 与成年组[EBPM(6.25±1.60)分;TBPM(5.38±0.87)分]相比,老年组的EBPM[(2.50±0.85)分和TBPM(4.93±1.07)分]均较成年组差(P＜0.01,P＜0.05),而EBPM损伤指数的差异亦有统计学意义(P＜0.01).老年组前瞻性记忆的EBPM和TBPM存在双分离.结论 老年人存在前瞻性记忆的损害,EBPM损害较TBPM损害更为显著.EBPM和TBPM的双分离表明其可能有不同的神经机制,推测额叶可能特异性地参与了EBPM.     

Signal-to-noise ratio effects in quantitative cerebral perfusion using dynamic susceptibility contrast agents.

Theoretical and simulation evidence is presented in support of the idea that the optimal manner of determining blood flow from MR perfusion studies is not necessarily obtained by setting experimental conditions to maximize either the arterial input or the measured tissue concentration level for a particular echo time (TE). The noise power in the contrast concentration curve is associated with its peak because of the nonlinear relationship between the contrast concentration and MR signal intensity curves. The optimum signal-to-noise ratio (SNR), SNR(C), for a particular contrast concentration curve can be obtained when the experimental concentration level and TE are adjusted to produce an MR intensity curve whose signal loss is 63% of the precontrast MR signal intensity. It is demonstrated that the stability of the singular valued decomposition (SVD) deconvolution approach to determine blood flow parameters is increased when the tissue curve maximum signal loss is in the range of 40-80%. The accuracy and stability of the SVD-determined blood flow parameters are affected by deviations from these optimum conditions in a manner that depends on the mean transit time (MTT) associated with the residue function. It is recommended that the experimental TE value be set so that neither the tissue nor the arterial curves are placed a region of rapidly deteriorating SNR(C).     

Designed polyanionic coiled-coil proteins: acceleration of heparin cofactor II inhibition of thrombin

Novel polyanionic proteins were designed to increase the rate of heparin cofactor II (HC) inhibition of α-thrombin, an essential protease in the coagulation cascade. Two α-helical coiled-coil proteins, a 62-residue dimer containing 8 Glu residues (E8C) and a 104-residue dimer containing 14 Glu residues (E14C), plus two 31-residue control peptides containing 8 Glu residues each (E8A and E8B), were chemically synthesized, structurally characterized and enzymatically assayed. Circular dichroic spectrophotometry indicated that both E8C and E14C formed stable two-chain α-helical coiled coils at pH 7 and 25 °C. The control peptides were only partially α-helical. E14C remained folded at 90 °C but E8C was half unfolded at 49 °C. Coiled-coil proteins E8C and E14C maximally accelerated by 35- and 33-fold, respectively, the rate of HC inhibition of α-thrombin. None of these compounds accelerated antithrombin inhibition of α-thrombin, and neither control peptide accelerated HC inhibition of α-thrombin. Acceleration of the HC inhibition of α-thrombin showed bimodal dependence on the concentration of the polyanionic protein, which is consistent with formation of a HC-coiled-coil-thrombin ternary complex. The results suggest that antithrombotic polyanionic α-helical coiled-coil proteins can be designed and synthesized and that the occurrence of secondary structure can be correlated with biologcal activity. © Munksgaard 1995.     

173例支气管哮喘特异性脱敏治疗的进一步评价

对173例支气管哮喘特异性脱敏治疗的疗效及影响疗效的因素进行了分析。结果表明:显效为30.6%(53/173).有效为56.1%(97/173),无效为13.3%(23/173)。影响疗效的因素与病情的程度有关,而与年龄、病程、皮试阳性反应强弱及脱敏治疗前4个疗程内是否应用曲安缩松等无关。并对特异性脱敏治疗支气管哮喘的优缺点进行讨论。     

Analysis of clozapine response and polymorphisms of the dopamine D4 receptor gene (DRD4) in schizophrenic patients

We have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48-bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre-and post-treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and response by analysis of variance. We conclude that the variation of the number of 48-bp repeats alone does not determine response to clozapine. Larger studies are underway to determine if there is a more subtle relationship with sequence variation within the repeats or at other polymorphic sites within the gene that may provide evidence for a component of clozapine's action being at D4 receptors. © 1995 Wiley-Liss, Inc.     

Eight years'' experience with a structured clinical examination

A structured clinical examination has been an integral component of the final-year examinations conducted by the Departments of Medicine and Surgery at the University of Adelaide for the last 8 years. It has been used as an alternative to the traditional clinical examination. This paper describes the results of ongoing student and examiner surveys carried out to determine their views and satisfaction with this new approach. It also briefly discusses the feasibility of introducing such an examination into a conventional medical school environment. The surveys showed a remarkable level of acceptance and support by both students and examiners. This positive reaction has been maintained over the 8-year period. The main reasons seem to be its perceived relevance and fairness. Students also appear to be directing their learning in a direction thought desirable by teachers. No significant problems have been encountered with the practical implementation of the method.     

Retrograde air insufflation in MRI: A technical note

Retrograde air insufflation was employed to distend the colon and the ileum in 18 patients and five volunteers for magnetic resonance examination. Good and moderate marking of the ileum was obtained in 18 cases. The colon was nearly completely distended in every case. Intraluminal tumor, mural thickening, and extraluminal lesion were outlined by intraluminal air and surrounding air-distended bowel. This study shows that retrograde air insufflation is a useful method to mark the colon and most parts of the ileum.     

An Evaluation of Technetium-99m Tin Colloid--Its Value in the Diagnosis of Renal Transplant Rejection

The value of the Technetium-99m tin colloid (TTC) scan in thediagnosis of renal transplant rejection occurring more than1 month following transplantation was assessed. To our knowledge,use of this agent has not previously been reported. Gamma cameraimaging was performed on 15 occasions in 14 patients in whomplasma creatinine was rising and in three patients in whom renalfunction was stable. Both a qualitative and a quantitative assessmentof images was made. The radioactivity recorded over the graft at 12–16 mmpost injection was expressed as a percentage of that recordedat 0–4 min. In the nine patients in whom graft perfusionwas adequate to allow interpretation of the TTC scan and inwhom rejection was diagnosed by biopsy (six cases) or on clinicalgrounds (three cases), the index ranged from 45 to 153%. Intwo patients the graft was poorly perfused and the accumulationof TTC was predictably low despite the presence of rejection.In the seven patients with either a stable creatinine or withrising creatinine not due to rejection, the index ranged from5 to 43%. Previously reported studies have shown that sulphur colloidsmay be of value in diagnosing graft rejection. This study suggeststhat Tc99m tin colloid may be regarded as a suitable alternativescanning agent and that some simplification of data collectionand analysis can be achieved.