Genetic Etiologies of Mental Retardation: Issues for Interventions and Interventionists

This paper outlines some practical implications of new work on the behavioral effects of genetic mental retardation disorders. After describing historical and definitional issues concerning so-called behavioral phenotypes, we use Down syndrome and Williams syndrome to illustrate how specific genetic disorders might differentially predispose individuals to particular, etiology-related behaviors. We then explore educational and other intervention implications of such etiology-related behaviors, before ending with a discussion of the area's critical unresolved issues.     

Dizziness is associated with decreased vasoreactivity in right cerebral hemisphere for head-down manoeuvre--near-infrared spectroscopy study

To investigate the vasoreactivity of cerebral hemisphere in patients with dizziness and syncope, we compared changes in total haemoglobin (THbl) and regional oxygen saturation (rSO2) of the right and left frontal lobes in response to head-down manoeuvre. Ninety-six right-handed subjects (aged 59 +/- 19 years) were asked to perform a head-down or a standing manoeuvre. Head-down manoeuvre produced a greater increase in right side THbl in subjects under 70 years of age (8.5 +/- 3.1) when compared with subjects older than 70 years (0.40 +/- 0.08). In contrast, the head-down manoeuvre had no effects on left side THbl, irrespective of patient age. Similarly, the head-down manoeuvre resulted in a greater decrease of right side rSO2 in subjects under 70 years of age (-5.2 +/- 2.1%) when compared with subjects older than 70 years (0.31 +/- 0.9%). In contrast, the head-down manoeuvre had no effects on left side rSO2, irrespective of patient age. The head-down manoeuvre produced a smaller increase in right side THbl in subjects with dizziness (0.38 +/- 0.19) than in those without dizziness (9.4 +/- 3.5). A standing manoeuvre produced a smaller increase in right side THbl in subjects with syncope (-0.057 +/- 0.047) than in those without syncope (0.063 +/- 0.028). The head-down manoeuvre produced a decrease in right side rSO2 in subjects without dizziness (-6.4 +/- 2.4%) and a slight increase in right side rSO2 in subjects with dizziness (1.1 +/- 0.4%). Subjects with dizziness (67 +/- 2.1 years) were significantly older than those without dizziness (53 +/- 2.7 years) or those with syncope (44 +/- 4.2 years). These data indicate that reduced vasoreactivity to right hemispheric pressure changes is associated with dizziness in older subjects. Further, decreases in right hemispheric THbl during a standing manoeuvre are associated with syncope in relatively younger subjects.     

Drug-disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity

AIM

Inflammation is involved in the pathogenesis of cardiovascular diseases that includes reduced response to pharmacotherapy due to altered pharmacokinetics and pharmacodynamics. It is not known if these effects exist in general in all inflammatory conditions. It also remains unknown whether in a given population the effect is a function of disease severity. We investigated whether pharmacokinetics and pharmacodynamics of a typical calcium channel inhibitor are influenced by Crohn''s disease (CD), a disease for which the disease severity can be readily ranked.

METHODS

We administered 80 mg verapamil orally to (i) healthy control subjects (n = 9), (ii) patients with clinically quiescent CD (n = 22) and (iii) patients with clinically active CD (n = 14). Serial analysis of verapamil enantiomers (total and plasma unbound), blood pressure and electrocardiograms were recorded over 8 h post dose. The severity of CD was measured using the Harvey-Bradshaw Index.

RESULTS

CD substantially and significantly increased plasma verapamil concentration and in a stereoselective fashion (S, 9-fold; R, 2-fold). The elevated verapamil concentration, however, failed to result in an increased verapamil pharmacodynamic effect so that the patients with elevated verapamil concentration demonstrated no significant increase in response measured as PR interval and blood pressure. Instead, the greater the disease severity, the lower was the drug potency to prolong PR interval (r = 0.86, P < 0.0006),

CONCLUSIONS

CD patients with severe disease may not respond to cardiovascular therapy with calcium channel blockers. Reducing the severity increases response despite reduced drug concentration. This observation may have therapeutic implication beyond the disease and the drug studies herein.     

预防长期住院高龄患者跌倒的护理干预

目的探讨长期住院高龄患者跌倒的危险因素及预防对策。方法对我院老年病区258例患者采取预防跌倒知识的宣教等干预,并对其效果进行分析总结。结果98．5％的患者或家属不同程度掌握了跌倒相关危险因素及预防措施的知识,老年患者在住院期间无跌倒发生。结论护理干预能有效地预防老年人跌倒,对提高老年人生活质量有重要意义。     

流动引物PCR高效筛选阳性XRCC1基因敲除小鼠细胞的方法

[目的]探索流动引物PCR筛选阳性XRCC1基因敲除细胞的可行性。[方法]构建基因敲除质粒,嘌呤霉素抗性基因5’端加上额外的来自野生型基因被敲除位点内的20 bp DNA序列。使用流动引物(floating primer)和这20 bp序列结合,PCR筛选阳性克隆。[结果]利用流动引物成功筛选小鼠体细胞XRCC1(X射线修复交叉互补蛋白)一个等位基因敲除的阳性克隆子。[结论]流动引物PCR方法可以应用于基因敲除小鼠体细胞的筛选。     

TCR down-regulation boosts T-cell-mediated cytotoxicity and protection against poxvirus infections

Cytotoxic T (Tc) cells play a key role in the defense against virus infections. Tc cells recognize infected cells via the T-cell receptor (TCR) and subsequently kill the target cells by one or more cytotoxic mechanisms. Induction of the cytotoxic mechanisms is finely tuned by the activation signals from the TCR. To determine whether TCR down-regulation affects the cytotoxicity of Tc cells, we studied TCR down-regulation-deficient CD3γLLAA mice. We found that Tc cells from CD3γLLAA mice have reduced cytotoxicity due to a specific deficiency in exocytosis of lytic granules. To determine whether this defect was reflected in an increased susceptibility to virus infections, we studied the course of ectromelia virus (ECTV) infection. We found that the susceptibility to ECTV infection was significantly increased in CD3γLLAA mice with a mortality rate almost as high as in granzyme B knock-out mice. Finally, we found that TCR signaling in CD3γLLAA Tc cells caused highly increased tyrosine phosphorylation and activation of the c-Cbl ubiquitin ligase, and that the impaired exocytosis of lytic granules could be rescued by the knockdown of c-Cbl. Thus, our work demonstrates that TCR down-regulation critically increases Tc cell cytotoxicity and protection against poxvirus infection.     

转移睾丸精索鞘膜修补尿道下裂术后尿瘘

目的:探讨尿道下裂术后尿瘘的修复方法,总结手术经验,提高手术成功率。方法:收集本院从2002年9月至2008年12月46例尿道下裂术后尿瘘修补术患者的临床资料,平均年龄11.7岁(3～26岁),共52个瘘口,瘘口直径均小于5mm,其中阴茎体部25例,阴茎阴囊交界处12例,阴囊处9例,分别采用连续内翻缝合法修补20例,转移睾丸精索鞘膜修补26例。结果:连续内翻缝合法一次修补成功率为55%(11/20),加用转移睾丸精索鞘膜修补一次成功率为84.6%(22/26)。结论:在连续内翻缝合的基础上,加用转移睾丸精索鞘膜修补尿瘘有更高的成功率。     

Computerized acoustic cardiographic insights into the pericardial knock in constrictive pericarditis

BACKGROUND: One of the clinical hallmarks of constrictive pericarditis is the pericardial knock, a high-pitched early diastolic heart sound. Making the clinical diagnosis of constrictive pericarditis is challenging, as is accurate auscultation of the pericardial knock. HYPOTHESIS: We sought to assess the utility of a computerized acoustic cardiographic device in the assessment of the pericardial knock in patients with constrictive pericarditis. METHODS: We report a case series in which computerized acoustic cardiography (Audicor, Inovise Medical Inc., Portland, OR) is performed in patients with constrictive pericarditis. RESULTS: Three patients with constrictive pericarditis underwent computerized acoustic cardiographic recordings at the time of cardiac catheterization. In each case, initial physical examination by the internist and referring cardiologist did not appreciate a pericardial knock. Acoustic cardiography demonstrated a high-pitched early diastolic sound in each case. Time-frequency representation analyses showed the high-frequency components of the pericardial knock sound. Repeat acoustic cardiography demonstrated resolution of the pericardial knock after pericardiectomy in two patients. CONCLUSIONS: Non-invasive computerized acoustic cardiography can demonstrate the high-pitched pericardial knock in patients with constrictive pericarditis. This may aid the bedside assessment of patients with diastolic heart failure, improving the clinician's ability to appreciate the ausculatory findings in constrictive pericarditis.     

加味白头翁汤治疗溃疡性结肠炎（湿热下注证）临床观察

目的：为探讨治疗溃疡性结肠炎（湿热下注证）的有效方法。方法：选住院及门诊患者60例,采用加味白头翁汤口服,对其临床疗效进行观察。结果：总有效率98.3%,治愈率63.3%。结论：该组中汤药对溃疡性结肠炎（湿热下注证）治疗效果明显,经济、方便、适用。     

Permanent endovenous pediatric pacing: absence of lead failure--20 years follow-up study

Background: The aim of the study was to analyze endovenous pacing lead survival in pediatric population implanted by cephalic cut down, or by axillary vein puncture.
Methods: All implantations were performed in total endotracheal anesthesia, by the same surgeon. Implantations of ventricular leads were performed by cephalic vein cut down or by external jugular vein preparation. In dual-chamber pacing, atrial leads were implanted via cephalic vein (along with ventricular lead), by axillary vein puncture or via external jugular vein. All implanted leads were secured by resorbable suture.
Results: Over the 20-year follow-up period, 105 children of 5.7 years average age (range 1 day–15 years) were implanted with a permanent endovenous pacing system for congenital or postsurgical complete atrioventricular block or sinus node disease. Within the group, 27 patients (25.7%) weighed less than 10 kg on implantation. A total of 121 endovenous leads were implanted. All ventricular leads were with a passive fixation mechanism, and most of them unipolar (87.6%) and steroid eluting (94.2%). Leads implanted in atrial position were 82% bipolar, predominantly with active fixation (94%), and all steroid eluting. The most frequently used mode of stimulation was VVIR (66.6%). No acute or chronic lead displacement, exit block, sensing problem, lead conductor fracture, insulation defect or infections were observed during the total follow-up of 709 pacing years (average 6.9, range 0–20 years).
Conclusion: Implantation of the endovenous leads by preparation of the cephalic or puncture of the axillary vein, with lead fixation by resorbable suture represents a method of choice.