Fabry disease in genetic counseling practice: recommendations of the National Society of Genetic Counselors

The objective of this document is to provide health care professionals with recommendations for genetic counseling and testing of individuals with a suspected or confirmed diagnosis of Fabry disease, with a family history of Fabry disease, and those identified as female carriers of Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as an individual with Fabry disease who is a founder of a Fabry disease patient advocacy group in the United States. The recommendations are U.S. Preventive Task Force Class III, and they are based on clinical experience, a review of pertinent English-language articles, and reports of expert committees. This document reviews the genetics of Fabry disease, the indications for genetic testing and interpretation of results, psychosocial considerations, and references for professional and patient resources. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a healthcare provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.     

Mechanisms of long-term dark adaptation

It has previously been suggested that long-term dark adaptation is controlled by bleaching signals that regulate the activity of an allosteric, positively cooperative protein (Stabell et al., 1986a, b). Recent biochemical evidence strongly supports this assumption, indicating that the primary regulator of the light-sensitive channels in the plasma membrane of the outer segments of the photoreceptors is a homo-oligomeric, allosteric, positively cooperative protein. In this report, we discuss the possibility that signals from bleached photopigments may control the dark-adaptation process through the allosteric protein of the plasma membrane. It is suggested that the concentrations of the bleached photopigment and of the allosteric effector are reciprocal quantities.     

MTHFR and ACE gene polymorphisms and risk of vascular and degenerative dementias in the elderly

Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as degenerative dementia. Among genetic factors, role of angiotensin converting enzyme (ACE) and methylene-tetrahydrofolate reductase (MTHFR) genes as putative risk factors has been examined but the outcome of these studies remain inconclusive. Present study attempted to see the importance of ACE alu insertion/deletion and MTHFR C677T polymorphisms as genetic predisposers to dementia. The study comprised of 80 vascular dementia patients, 90 degenerative dementia patients and 170 age matched controls. All were genotyped for ACE, MTHFR and APOE polymorphisms using PCR-RFLP method. Frequency of ACE D allele was seemingly high in dementia cases (26.7%) when compared to controls (11.2%). However, after adjusting for age and APOE E4^*, none of the ACE alleles showed good correlation. MTHFR genotypes or alleles also did not show any correlation. Our study suggests no true correlation of ACE or MTHR genes with dementia in elderly.     

羟苯磺酸钙与培哚普利对早期糖尿病肾病大鼠的治疗作用比较

观察羟苯磺酸钙和培哚普利对早期糖尿病肾病大鼠肾脏的治疗作用的差别。测定24h尿白蛋白,血浆及肾皮质ET（内皮素,endothelin）含量,肾皮质PAI-1（纤溶酶原激活物抑制剂-1,plasminogen activator inhibitor-1）、MMP-9（基质金属蛋白酶-9,matrix metalloproteinase-9）表达,观察肾脏病理形态变化。从结果看,羟苯磺酸钙可以减轻实验大鼠肾脏损伤,作用与培哚普利无明显差别。     

ACE与体外循环后心肌损伤的关系

观察体外循环后血管紧张素转换酶（ACE）及心肌标志物的变化,探讨ACE与心肌损伤之间的关系。20例择期CPB心脏手术患者分别于术前（T1）、CPB60rain（T2）、CPB后30min（T3）、4h（T4）、24h（T5）及48h（T6）各时间点测定静脉血中下列各指标的水平：ACE、肌钙蛋白I（cTnI）、肌红蛋白（...     

Dark-adaptation mechanisms of the long-wave foveal cones

The ordinary long-term rod and cone dark-adaptation curves have generally been assumed to follow a single exponential rate of recovery. However, in two previous papers on rod dark-adaptation (Stabell et al., 1986a, b), the recovery curve was found to consist of three different sections. The results of the present paper show the same type of recovery function with three different sections for the long-term dark-adaptation curve of the long-wave cone system. During the major, middle section log cone threshold, like log rod threshold, is linearly related to the logarithm of the concentration of bleached photopigment. Presupposing that the bleached cone photopigment acts as a ligand, the change in threshold level obtained during the middle section of the dark-adaptation curve is well described by the change in activity rate of an allosteric, postively cooperative enzyme built as a dimer.     

Long-term rod dark adaptation in man. Threshold measurements, rhodopsin regeneration and allosteric sensitivity regulation. An evaluation

Recent evidence strongly suggests that the relationship between threshold elevation ( T ) and fraction of bleached rhodopsin ( B ), obtained during a major, middle period of long-term rod dark adaptation in man, is well described by a power function, i. e., T = k · Bⁿ , where k is a multiplicative constant and n is the exponent. Due primarily to the low reliability of measurements of rhodopsin regeneration, however, the exponent n of the power function cannot, at present, be given an exact value. Available information indicates that the value of the exponent ranges between 2.4 and 4. Implications of this uncertainty are discussed within the framework of the allosteric, tetrameric model of rod dark adaptation. It is concluded that this model in its simplest form may only offer a first approximation of the real system implicated in the process.     

Dark adaptation of the long-wave cones at different eccentricities

Using a Wright colorimeter the ordinary long-term, long-wave cone dark-adaptation curve was measured at 0, 2, 4, 7, 17, 25, 40 and 49 degrees nasally in the visual field. In opposition to previous findings, the results show that the dark-adaptation function of the long-wave cones changes markedly when the test field is moved outward from the rod-free fovea. It is suggested that the kinetics of the long-wave cone photopigment change with eccentricity. Also, at variance with previous findings, the present curves at all eccentricities may reasonably well be interpreted as consisting of three different sections; a first section where the threshold decreases rapidly, followed by a major, approximately linear section and a terminating section that converges asymptotically towards the final level of sensitivity. This finding suggests that the dark-adaptation process of the cone system, under the given experimental conditions, is based on three somewhat different processes.     

血管紧张素转换酶抑制剂与心肌缺血再灌注的细胞凋亡

随着心脏外科手术和介入治疗技术的进展以及心肌缺血患者的增加,心肌缺血再灌注损伤成为临床工作一种常见的病理生理过程。如何采用有效的治疗手段进行心肌保护,防治或降低缺血再灌注所造成的损伤,一直是心脏科学探索的一个重要课题。血管紧张素转化酶抑制剂对很多心脏疾病的治疗特别是拟行心脏手术患者的治疗都取得了良好的效果。随着对其研究的进展,其预处理可为临床预防治疗心肌缺血再灌注损伤提供思路与方法。     

关于血管紧张素转换酶抑制药＋β受体阻断药组合的重新审视

采取联合用药方案治疗高血压已成为近年来临床用药的总体趋势。临床用药情况调查结果表明,血管紧张素转换酶抑制药＋β受体阻断药的联合用药组合占有一定的使用率,分析两类药的降压作用以及对高血压常见并发症和对代谢、心率等的影响,可见这个组合是合理的。