Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

In the present study, we address the role of the gene for catechol-O-methyltransferase (COMT), a key modulator of dopaminergic and noradrenergic neurotransmission, in the genetic predisposition to obsessive-compulsive disorder (OCD). We show that a common functional allele of this gene, which results in a 3- to 4-fold reduction in enzyme activity, is significantly associated in a recessive manner with susceptibility to OCD, particularly in males. This association is further supported by psychiatric evaluation of patients who carry microdeletions encompassing the comt gene. The mechanism underlying this sex-selective association remains to be defined and may include a sexual dimorphism in COMT activity, although close linkage with a nearby disease susceptibility locus cannot be excluded at this point.     

Impact of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) on the speed of triage decision making for emergency department patients presenting with chest pain

Objective: Emergency department (ED) triage for acute cardiac ischemia in the primary teaching hospital in Geneva, Switzerland, is very accurate, but at the cost of very long ED stays. Thus, the authors sought: 1) to determine the impact of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), incorporated into a computerized electrocardiograph, on length of stay and speed of triage decision making for ED patients presenting with symptoms suggesting acute cardiac ischemia, and 2) to study the ACI-TIPI’s impact on physicians of different training levels. Design: A seven-month prospective clinical trial with alternating-month experimental and control periods. Setting: An urban major teaching hospital in Geneva, Switzerland. Participants: Patients over the age of 18 years presenting to the ED with chest pain or other symptoms suggesting acute cardiac ischemia (acute myocardial infarction or unstable angina pectoris). Emergency department physicians, classified as novice (those in their first ED rotations) and experienced (those in their second or later ED rotations). Patients staying overnight in the ED (n=111) were excluded from the analysis. Intervention: During the experimental months, the computerized electrocardiograph printed the ACI-TIPI probability of acute cardiac ischemia at the top of each subject’s electrocardiogram. During control months, the probability was not provided. Measurements and main results: Among the 418 study subjects, for patients with acute ischemia seen by novice clinicians, the use of the ACI-TIPI decreased ED time from presentation to triage decision and ED release by 0.7 hour (19%) (p=0.007). Subgroup analyses for patients with acute myocardial infarction, patients with unstable angina pectoris, and patients given thrombolytic therapy also showed analogous decreases in ED time consistent with this finding. Other key determinants of ED length of stay included: age, whether the coronary care unit was full, whether patients received thrombolytic therapy, and whether admission was during the night shift. The experimental and control groups did not differ in triage disposition appropriateness or mortality. Conclusions: For ED patients with acute cardiac ischemia evaluated by novice clinicians, the ACI-TIPI substantially speeded ED decision making and triage. The suggestion of an impact on different cardiac ischemia subgroups and mortality deserves further larger clinical trials.     

坦桑尼亚摩省明都学校血吸虫病流行特点分析

阐明坦桑尼I明都地区曼氏血吸虫病和埃及血吸虫病感染特性，为该地区防治工作提供科学的依据。方法1995年11月我们对坦桑尼亚摩省明都小学241名6～18岁的学生进行了粪检和尿检，结果曼氏血吸虫病的感染率为80．5％．埃及血吸虫病的感染率为50．9％。其中粪检和尿检两项阳性者占39．7％，两相阴性者只占8．5％，粪检阳性尿检阴性者占40．6％和尿检阳性粪检阴性者占11．2％。结论曼氏血吸虫病感染率女性略高于男性，而埃及血吸虫病感染率则男性高于女性，感染率和感染度基本上一致。     

Separation of adeno-associated virus type 2 empty particles from genome containing vectors by anion-exchange column chromatography

Adeno-associated virus (AAV) empty capsids typically co-purify with genome containing AAV2 vectors purified by column chromatography. This study describes a method to remove empty capsids from genome containing vector particles by anion exchange chromatography. The separation is based on the slightly less anionic character of empty particles compared to vectors. Detailed methods to achieve AAV2 vector purification and particle separation using cation exchange resin POROS 50HS followed by anion exchange resin Q-Sepharose^xl are described. Chromatographic separation of AAV2 particles was achieved using gradients based on sodium acetate and ammonium acetate, and was optimal at pH 8.5. Efficient removal of particle surface nucleic acid impurities was found to be important to achieve good particle separation. In a large scale experiment performed using partially purified vector containing a mixture of 1.56 × 10¹⁴ vg and 2.52 × 10¹⁵ empty capsids as a starting material, the optimized anion exchange chromatography method resulted in a vector peak of 1.15 × 10¹⁴ vg containing 0.25 × 10¹⁴ empty capsids, corresponding to 74% vector yield and 86-fold reduction in empty capsids in the vector product.     

Extended access oxycodone self-administration and neurotransmitter receptor gene expression in the dorsal striatum of adult C57BL/6 J mice

Rationale

Although non-medical use of oxycodone continues to be a growing problem in the United States, there are no animal studies examining the effects of long-term oxycodone self-administration (SA).

Objectives

The current study was designed to examine chronic oxycodone SA by mice (14 days), in novel extended (4 h) SA sessions and its effect on selective striatal neurotransmitter receptor mRNA expression.

Methods

Adult male C57/BL6J mice were either allowed to self-administer oxycodone (0.25 mg/kg/infusion, FR1) or served as yoked-saline controls in an extended access paradigm. Mice self-administered oxycodone for 4 h/day for 14 consecutive days. Comparison groups with 14-days exposure to 1-h SA sessions were also studied. Within 1 h of the last extended SA session, mice were sacrificed, dorsal striatum was isolated and selective neurotransmitter receptor mRNA levels were examined.

Results

The oxycodone groups poked the active hole significantly more times than the yoked controls. The number of nose pokes at the active hole rose over the 14 days in the oxycodone group with extended access. The expression of 13 neurotransmitter receptor mRNAs was significantly altered in the dorsal striatum, including the gamma-aminobutyric acid (GABA) A receptor beta 2 subunit (Gabrb2) showing experiment-wise significant decrease, as a result of extended oxycodone SA.

Conclusion

C57BL/6 J mice escalated the amount of oxycodone self-administered across 14 consecutive daily extended sessions, but not 1-h sessions. Decreases in Gabrb2 mRNA levels may underlie escalation of oxycodone intake in the extended access SA sessions.     

Efficiency of single-nucleotide polymorphism haplotype estimation from pooled DNA

The efficiency of single-nucleotide polymorphism haplotype analysis may be increased by DNA pooling, which can dramatically reduce the number of genotyping assays. We develop a method for obtaining maximum likelihood estimates of haplotype frequencies for different pool sizes, assess the accuracy of these estimates, and show that pooling DNA samples is efficient in estimating haplotype frequencies. Although pooling K individuals increases ambiguities, at least for small pool size K and small numbers of loci, the uncertainty of estimation increases 相似文献   

Estimating parental relationship in linkage analysis of recessive traits

In linkage analysis of recessive traits, parental relationship is important. For the case that it is unknown, the question is investigated as to whether estimating parental relationship and using the estimated relationship in linkage analysis is beneficial. Results show that estimating parental relationship can reliably be carried out on the basis of 50–100 genetic marker loci (analysis based on theory by Thompson [1975: Am J Hum Genet 39:173–188]). Misspecification of parental relationship leads to a loss of linkage informativeness, but not to false-positive evidence for linkage. An asymptotic bias in the recombination fraction estimate occurs when parents are unrelated and falsely taken to be related, but no such bias is seen when related parents are taken to be unrelated. Results from this investigation suggest that an estimated parental relationship may be used in linkage analysis as if it were the correct relationship, when evidence for the estimated relationship is supported by a likelihood ratio of at least 10:1 against the parents being unrelated. © 1996 Wiley-Liss, Inc.     

Iliac graft access to facilitate endovascular repair of a ruptured thoracic aortic aneurysm -- a case report

Arterial access for endovascular aortic aneurysm repair is usually gained through a common femoral artery approach. In small femoral arteries this can be difficult or even impossible owing to the large size of the introduction sheath of the delivery system. In such cases the iliac arteries or the abdominal aorta can be used for vascular access, although, in heavily calcified arteries,even this can be hazardous. The authors report an 81-year-old woman with a contained rupture of the thoracic aorta in whom a polyester graft was used to facilitate vascular access to the common iliac artery for a safe two-stage endovascular repair of the aneurysm.     

Bilateral stimulation of the subthalamic nucleus in Parkinson's disease: surgical efficacy and prediction of outcome

OBJECTIVE: Over the last decade neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson's disease. Previously, we have addressed safety and efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS). In this study, we extended these observations and analyzed factors that affect surgical outcome and its predictive value. METHODS: Thirty-nine patients were enrolled in an open-label prospective protocol designed to evaluate safety and efficacy of bilateral STN DBS in patients with advanced Parkinson's disease between January 1999 and July 2002. Electrodes were stereotactically implanted with electrophysiological conformation of the target location. All patients were evaluated in the medication 'off' and 'on' state preoperatively and at 3, 6, and 12 months after surgery in medication 'on' and 'off' as well as in the stimulation 'off' and 'on' state. Tests included Unified Parkinson's Disease Rating Scales (UPDRS) as well as timed tests. All data was analyzed by means of Analysis of Variance. For outcome prediction, correlation and linear regression analyses were utilized. Stimulation produced significant improvements in all 'off' mediation conditions, resulting in a 42% improvement in UPDRS III score at 12 months compared to the preoperative status. Stimulation in conjunction with medication did not produce any significant change when compared to the preoperative medication 'on' state. Dyskinesia, motor fluctuations, and duration of 'off' periods were significantly reduced with stimulation. Significant outcome predictor variables were age, preoperative percent change of UPDRS III score from medication 'off' to medication 'on' state, and the duration of disease. CONCLUSIONS: Bilateral STN DBS produces robust improvements in parkinsonian motor symptoms. Surgical outcome can reliably be predicted.