Muscle fiber dysfunction contributes to weakness in inclusion body myositis

Atrophy and fatty infiltration are important causes of muscle weakness in inclusion body myositis (IBM). Muscle weakness can also be caused by reduced specific force; i.e. the amount of force generated per unit of residual muscle tissue. This study investigates in vivo specific force of the quadriceps and ex vivo specific force of single muscle fibers in patients with IBM. We included 8 participants with IBM and 12 healthy controls, who all underwent quantitative muscle testing, quantitative MRI of the quadriceps and paired muscle biopsies of the quadriceps and tibialis anterior. Single muscle fibers were isolated to measure muscle fiber specific force and contractile properties. Both in vivo quadriceps specific force and ex vivo muscle fiber specific force were reduced. Muscle fiber dysfunction was accompanied by reduced active stiffness, which reflects a decrease in the number of attached actin-myosin cross-bridges during activation. Myosin concentration was reduced in IBM fibers. Because reduced specific force contributes to muscle weakness in patients with IBM, therapeutic strategies that augment muscle fiber strength may provide benefit to patients with IBM.     

Genetic susceptibility for human familial essential hypertension in a region of homology with blood pressure linkage on rat chromosome 10

Hypertension is a significant risk factor for heart attack and stroke and represents a major public health burden because of its high prevalence (e.g. 15-20% of the European and American populations). Although blood pressure is known to have a strong genetic determination, the genes responsible for susceptibility to essential hypertension are mostly unknown. Loci involved in blood pressure regulation have been found by linkage in experimental hereditary hypertensive rat strains, but their relationship to human hypertension has not been extensively investigated. One of the principal blood pressure loci has been mapped to rat chromosome 10 and we have undertaken an investigation of the homologous region on human chromosome 17 in familial essential hypertension. Affected sib-pair analysis and parametric analysis with ascertainment correction gave significant evidence of linkage ( P <0.0001 in some analyses) near two closely linked microsatellite markers, D17S183 and D17S934, that reside 18 cM proximal to the ACE locus in the homology region. Our results indicate that chromosome 17q could contain a susceptibility locus for human hypertension and show that comparative mapping may be a useful approach for identification of such loci in humans.      

血管成形术和支架辅助血管成形术治疗颅内动脉粥样硬化的报告标准（上）

背景和目的颅内动脉粥样硬化可造成众多患者发生缺血性卒中。过去10年间血管内治疗技术已经取得突破性进展,能够开展颅内动脉粥样硬化性狭窄的血管内治疗。采用血管成形术和支架辅助阻管成形术治疗颅内动脉粥样硬化性狭窄的患者例数不断增加。但是鉴于目前血管成形术和支架辅助血管成形术治疗狭窄性和闭塞性颅内动脉粥样硬化仍缺乏普遍认可的临床和放射学评估以及皿管内治疗技术及预后的规范,此文就是提供该方面报告标准、术语和书面定义的共识性建议。报告摘要报告标准是在技术评价委员会、神经介入外科学会、介入放射学会、美国神经外科医师协会和神经外科医师代表大会的脑血管外科分会、美国神经科学会的卒中和介入神经病学分会的联合写作组共同起草完成。对1997年1月-2007年12月间,美国国立图书馆医学文献数据库（PubMed）进行计算机检索,旨在确定已发表的狭窄性颅内动脉粥样硬化的神经介入治疗中,能用作质量评价基准的资料。我们尽可能地确定影响神经介入治疗成功及并发症可能性的危险调节变量。对狭窄性和闭塞性颅内动脉粥样硬化进行麻管内治疗的临床试验设计中,不同临床和技术问题可能影响血管内治疗的疗效,此文章为这些问题提供相关的理论基础。该指南中包括对血管内治疗试验报告标准的建议。虽然制定规范和标准主要是出于研究用途,但是这也将有助于临床实践,还适用于所有相关的出版物。结论总之,报告标准提出的建议将有助于构建有效的研究数据库,同时促进产生科学可靠的研究结果,使相似研究之间或内部能够进行可靠的比较。存某些情况下,为报告和出版的一致性,本文中的定义可能是写作组专家的共识性建议。这些建议将促使不同研究组的结果具有直接可比性。     

Doppler-derived mitral deceleration time: an early strong predictor of left ventricular remodeling after reperfused anterior acute myocardial infarction

BACKGROUND: The relation between remodeling and left ventricular (LV) diastolic function has not yet been fully investigated. The aim of this study was to determine whether early assessment of Doppler-derived mitral deceleration time (DT), a measure of LV compliance and filling, may predict progressive LV dilation after acute myocardial infarction (AMI). METHODS AND RESULTS: Fifty-one patients (aged 61+/-11 years; 6 women) with anterior AMI successfully treated with direct coronary angioplasty underwent 2-dimensional and Doppler echocardiographic examinations within 24 hours of admission, at days 3, 7, and 30 and 6 months after the index infarction. Mitral flow velocities were obtained from the apical 4-chamber view with pulsed Doppler. End-diastolic volume index (EDVI) and end-systolic volume index (ESVI) were calculated with the Simpson's rule algorithm. Patients were divided according to the DT duration assessed at day 3 in 2 groups: group 1 (n=33) with DT >130 ms and group 2 (n=18) with DT 相似文献   

The specific antigen-binding cell populations of individual fetal mouse spleens: repertoire composition, size, and genetic control

In order to analyze the genetic and physiological basis of controls affecting the generation of the repertoire of antigen-binding cells in fetal mice, we have measured the numbers of spleen cells specific for each of four antigens as a function of the total numbers of nucleated and Ig-bearing cells in inbred, hybrid, and random bred fetuses. For each of the two inbred strains BALB/c and CBA/J, the proportion of nucleated cells specific for a given antigen was the same for all individuals of the strain at the 18th day of gestation. The proportion did vary from antigen to antigen, however, and for each antigen the proportion of specific cells observed in CBA/J fetuses was approximately four times that observed in BALB/c fetuses. This difference appeared to be due to a difference between the two strains in the relative size of the repertoire of antigen-binding spleen cells at this stage of development, inasmuch as the frequency of Ig-bearing spleen cells in CBA/J fetuses was likewise approximately four times that observed in BALB/c fetuses. In random bred Swiss-L fetal mice at the 18th day of gestation, the proportion of cells specific for a given antigen varied significantly from one individual to the next. The ratio of proportions of the two antigens observed was constant from individual to individual, however, and this constant ratio differed significantly from the ratio observed for the same two antigens in fetal BALB/c and CBA/J inbred mice. These data suggest that the ontogeny of the repertoire of antigen-binding cells in fetal mice is subject to at least two independent sets of controls, one affecting the relative size of the repertoire in the spleen, and the other affecting the distribution of antigen-binding specificities within that repertoire. Analysis of repertoire size and composition in the spleens of hybrid fetuses confirmed the observation that the two parameters are controlled independently, and suggested further that the control of repertoire size in these fetuses is due to the action of one or a few closely-linked autosomal Mendelian genes. These data are consistent with models for the origin of antibody diversity in which the genes coding for the full repertoire of antibodies are generated somatically from a small number of germ-line genes early in development and in the absence of any strong positive or negative selection with respect to antigenic specificity.     

Marrow transplantation from unrelated donors for treatment of hematologic malignancies: effect of mismatching for one HLA locus

One hundred twelve patients less than 36 years old received marrow grafts from unrelated donors as treatment for hematologic malignancy. Seventy donor/recipient pairs were phenotypically identical for HLA-A, - B, and -D, while 42 had a "minor" disparity at one HLA locus. There was an increase in the risk of acute graft-versus-host disease (GVHD) in patients receiving HLA-partially matched grafts compared with those receiving HLA-matched grafts (51% v 36% probability of grades III-IV acute GVHD). However, in this cohort of patients, there was no significant difference in survival (at 1.5 years, 46% v 51% for good- risk patients, 44% v 30% for poor-risk patients). This finding suggests that some degree of HLA disparity can be tolerated in young patients transplanted from unrelated donors for malignant disease, thus making transplantation an option available to larger numbers of patients.     

Recovery from unilateral neglect after right-hemisphere stroke

Purpose:?To show the recovery process for different forms of unilateral neglect (UN)—including personal neglect and neglect of far space—in relationship to impairment, disability, cognition and mood.

Method:?Patients were tested at 2?–?4 weeks, at 6 months and at 1 year. We used the Behaviour Inattention Test and a test for personal neglect. We also used the NIH Stroke Scale, the Functional Independence Measure (FIM), the Mini-Mental State Evaluation and the Geriatric Depression Scale.

Results:?Peripersonal neglect diminishes within 6 months, but complete recovery occurred in only 13%. The prognosis for personal neglect and neglect of far space is better, with a recovery ratio at 6 months of 52% and 46%, respective. The correlations between UN and FIM are high. A few patients deteriorate in the absence of recurrent stroke.

Conclusions:?For clinical purposes, it is practical to postpone UN evaluation until a couple of weeks after a stroke. Many of the patients who then have UN are likely to retain their UN, although many will improve. Patients with UN should receive special attention in the rehabilitation phase, as well as at discharge. One explanation of the worsening of UN seen in some patients, may be continuing cerebral atherosclerosis.