Pathophysiology of idiopathic dystonia: findings from genetic animal models

Dystonia is a common movement disorder which is thought to represent a disease of the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e. the neuroanatomic and neurochemical basis, is still a mystery. Research in dystonia is complicated by the existence of various phenotypic and genotypic subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions.In neurological diseases in which no obvious neuronal degeneration can be found, such as in idiopathic dystonia, the identification of a primary defect is difficult, because of the large number of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain.The variable response to pharmacological agents in patients with idiopathic dystonia supports the notion that the underlying biochemical dysfunctions vary in the subtypes of idiopathic dystonia. Hence, in basic research it is important to clearly define the involved type of dystonia.Animal models of dystonias were described as limited. However, over the last years, there has been considerable progress in the evaluation of animal models for different types of dystonia.Apart from animal models of symptomatic dystonia, genetic animal models with inherited dystonia which occurs in the absence of pathomorphological alterations in brain and spinal cord are described.This review will focus mainly on genetic animal models of different idiopathic dystonias and pathophysiological findings. In particular, in the case of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case of the genetically dystonic hamster (dt^sz), a model of paroxysmal dystonic choreoathetosis has been used, as these show great promise in contributing to the identification of underlying mechanisms in idiopathic dystonias, although even a proper animal model will probably never be equivalent to a human disease.Several pathophysiological findings from animal models are in line with clinical observations in dystonic patients, indicating abnormalities not only in the basal ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through clinical studies and neurochemical data several similarities were found in the genetic animal models, although the current data indicates different defects in dystonic animals which is consistent with the notion that dystonia is a heterogenous disorder.Different supraspinal dysfunctions appear to lead to manifestation of dystonic movements and postures. In addition to increasing our understanding of the pathophysiology of idiopathic dystonia, animal models may help to improve therapeutic strategies for this movement disorder.     

Interviewing skills: self-evaluation by medical students

In an independent learning project, 52 third-year medical students carried out a structured self-assessment of two videotaped psycho-social interviews they had conducted with volunteer clients 1 year earlier, as part of a previous course. The interviews had been conducted in small tutorials with feedback from their clients, fellow students and tutors, facilitated by videotape playback. During the sequence of 16 tutorials each student had carried out an early and a late interview and had observed and participated in the discussion of the interviews of 14 peers. Students were asked to tally the frequencies of various interview behaviours, to evaluate the quality of their behaviours, and to establish priorities for future learning. The videotapes were also reliably rated by an independent observer. Students' overall self-assessments correlated 0.46 with those of the independent observer. This correlation was higher than is typically reported in studies of the validity of self-assessment. In absolute terms, the students' mean rating of interviewing performance was 3.2 (adequate plus) which was significantly lower than the observer's mean of 3.6 (adequate to good). Results are discussed in terms of Gordon's (1992) two recommendations for improving the validity of self-assessments and two further suggestions, for paired comparisons and low-threat learning environments, are added.     

显微外科技术治疗周围神经陈旧性损伤

目的探讨应用显微外科技术治疗需再次手术的周围神经损伤的方法和疗效。方法对33例周围神经损伤第一次手术效果差的患者,应用显微外科技术进行再次手术治疗。结果本组获得随访30例,共41条神经,随访时间为9个月～6年,平均为27个月,优良率为73.2%。结论对周围神经损伤初次手术效果差的患者,应尽早再次手术探查,应用显微外科技术,选择合适的手术方式,可取得较满意的手术疗效。     

Low sodium haemodialysis reduces interdialytic fluid consumption but paradoxically increases post-dialysis thirst.

BACKGROUND: Interdialytic weight gain (IDWG) can be reduced by lowering the dialysate sodium concentration ([Na]) in haemodialysis patients. It has been assumed that this is because thirst is reduced, although this has been difficult to prove. We compared thirst patterns in stable haemodialysis patients with high and low IDWG using a novel technique and compared the effect of low sodium dialysis (LSD) with normal sodium dialysis (NSD). METHODS: Eight patients with initial high IDWG and seven with low IDWG completed hourly visual analogue ratings of thirst using a modified palmtop computer during the dialysis day and the interdialytic day. The dialysate [Na] was progressively reduced by up to 5 mmol/l over five treatments. Dialysis continued at the lowest attained [Na] for 2 weeks and the measurements were repeated. The dialysate [Na] then returned to baseline and the process was repeated. RESULTS: Baseline interdialytic day mean thirst was higher than the dialysis day mean for the high IDWG group (49.9+/-14.0 vs 36.2+/-16.6) and higher than the low weight gain group (49.9+/-14.0 vs 34.1+/-14.6). This trend persisted on LSD, but there was a pronounced increase in post-dialysis thirst scores for both groups (high IDWG: 46+/-13 vs 30+/-21; low IDWG: 48+/-24 vs 33+/-18). The high IDWG group demonstrated lower IDWG during LSD than NSD (2.23+/-0.98 vs 2.86+/-0.38 kg; P<0.05). CONCLUSIONS: Our results indicate that patients with high IDWG experience more intense feelings of thirst on the interdialytic day. LSD reduces their IDWG, but paradoxically increases thirst in the immediate post-dialysis period.     

原发性肝癌HBV感染模式与AFP水平相关性研究

目的:探讨原发性肝癌(PHC)患者乙肝病毒(HBV)感染模式与血清甲胎蛋白(AFP)水平的关系。方法:应用酶免疫检测法(ELISA)、聚合酶链反应(PCR)及放射免疫技术分别测定100例原发性肝癌患者血清乙型肝炎病毒指标(HBV-M)及AFP。结果:100例PHC患者中,HBV-M阳性88例(88％),阴性12例(12％),HBV-M阳性者AFP水平高于阴性者147 ng/mL,二者有非常显著性意义(P<0.01),且HBV-M阳性者AFP升高(68.4％)的比例明显高于HBV-DNA阴性者(31.6％)(P<0.01)。PHC患者HBV感染模式分析中,HBsAg、HBeAb、HBcAb阳性和HBV-DNA阳性最多,为56例(63.6％),其次为HBsAg、HBeAg、HBcAb和HBV-DNA阳性,为9例(10.2％)。结论:HBV是原发性肝癌发生的重要原因,在PHC患者中,AFP升高与HBV感染、复制相关。     

Natural history of parathyroid function and calcium metabolism after kidney transplantation: a single-centre study.

BACKGROUND: The natural history of parathyroid function after successful renal transplantation (RT) and the factors predisposing to persistent hyperparathyroidism (HPT) are not well established. A better knowledge of these data may be helpful in the development of algorithms for optimal surveillance and treatment of HPT after successful RT. Our aim was to evaluate the post-transplant natural history of parathyroid function and calcium metabolism in patients with a functional renal graft and to identify risk factors for persistent HPT. METHODS: Charts of 1165 allograft kidney recipients transplanted between 1989 and 2000 were reviewed. Patients with an intact parathyroid hormone (iPTH) level available at the time of transplantation were identified. The charts of the latter patients were checked for a variety of demographic and clinical data, and all determinations of the iPTH concentration available since transplantation were recorded. Serum levels of calcium, phosphorus, alkaline phosphatases and creatinine, concurrently determined, were also registered. RESULTS: After an initial fall, iPTH levels showed a slow but steady decline towards the upper normal limit. The prevalence of persistent HPT, defined as an iPTH level > or =2.5 times the upper normal limit or the need for parathyroidectomy following transplantation, remained stable at approximately 17% up to 4 years after transplantation. Patients with persistent HPT had significantly elevated serum levels of iPTH, calcium and phosphorus at the time of RT, and had spent a longer time on dialysis. Post-transplant iPTH levels correlated significantly with transplant kidney function. CONCLUSION: Kidney transplant recipients with a high iPTH and calcium x phosphate product at the time of transplantation are at risk for persistent HPT especially when renal function is suboptimal. Therapy for persistent HPT, if considered, should be initiated 3 months post-transplantation since further spontaneous improvement of parathyroid function thereafter is limited.     

Double-bundle technique: Endoscopic posterior cruciate ligament reconstruction using tibialis posterior allograft

Recently, attention has been given to the double-bundle technique for treating the posterior cruciate ligament (PCL)-deficient knee. We present an arthroscopic PCL reconstruction using a double-bundle technique with 3-stranded tibialis posterior (TP) allograft that has not been described before. The anterolateral bundle of the PCL is reconstructed using 2-stranded TP allograft and the posteromedial bundle using 1-stranded TP allograft. Three-stranded TP allograft will be an alternative graft choice for PCL reconstruction.     

人正、反义转化生长因子beta1基因真核表达载体的构建

目的 :构建人转化生长因子beta 1(TGFβ1)正、反义基因真核表达载体。方法 :从人胎脑的cDNA文库中扩增出TGFβ1共 12 84bp长的DNA片段后 ,与T载体直接进行高效连接 ,并测序证实无突变。接着利用TGFβ1引物两端所设计的酶切位点将目的片段定向亚克隆到真核表达载体pcDNA3.1( )。构建的正反义表达重组体 (pcDNA3.1 TGFβ1和pcDNA3.1 antiTGFβ1)经限制性内切酶消化证实其中有目的片段完整插入。结果 :本实验成功构建了人正、反义TGFβ1基因真核表达载体。结论 :人正、反义TGFβ1基因真核表达载体的构建 ,为今后研究腹膜纤维化的防治奠定了实验基础。     

父母亲社会经济状况与低出生体质量儿的相关性探讨

①目的 探讨父母亲社会经济状况与低出生体质量儿发生的关系。②方法 采用病例对照研究方法，对190名低出生体质量儿和750名正常出生体质量儿的父母亲进行了相关因素调查，用Logistic回归分析进行了危险因素分析。③结果 母亲年龄大于35岁、母亲的职业为教师或农民、父亲吸烟、母亲孕期吸烟及年家庭收人低是发生低出生体质量儿的危险因素(OR=1．280～7．290)，母亲身高与低出生体质量儿的发生率呈负相关关系(OR=0．898)。④结论 父母亲的社会经济状况与低出生体质量儿的发生有关。