Tracking motor impairments in the progression of Huntington's disease

The Unified Huntington's Disease Rating Scale is used to characterize motor impairments and establish motor diagnosis. Little is known about the timing of diagnostic confidence level categories and the trajectory of motor impairments during the prodromal phase. Goals of this study were to estimate the timing of categories, model the prodromal trajectory of motor impairments, estimate the rate of motor impairment change by category, and provide required sample size estimates for a test of efficacy in clinical trials. In total, 1010 gene‐expanded participants from the Neurobiological Predictors of Huntington's Disease (PREDICT‐HD) trial were analyzed. Accelerated failure time models were used to predict the timing of categories. Linear mixed effects regression was used to model the longitudinal motor trajectories. Age and length of gene expansion were incorporated into all models. The timing of categories varied significantly by gene expansion, with faster progression associated with greater expansion. For the median expansion, the third diagnostic confidence level category was estimated to have a first occurrence 1.5 years before diagnosis, and the second and first categories were estimated to occur 6.75 years and 19.75 years before diagnosis, respectively. Motor impairments displayed a nonlinear prodromal course. The motor impairment rate of change increased as the diagnostic confidence level increased, with added acceleration for higher progression scores. Motor items can detect changes in motor impairments before diagnosis. Given a sufficiently high progression score, there is evidence that the diagnostic confidence level can be used for prodromal staging. Implications for Huntington's disease research and the planning of clinical trials of efficacy are discussed. © 2013 International Parkinson and Movement Disorder Society     

苦绳的甾体成分

从苦绳(Dregea sinensis Hemsl.)中分离到两个新化合物∶苦绳甙元乙(dresigeninB,1)和苦绳甙I(dresiosideI,2)。经光谱和化学反应确定其结构为∶20-O-(2-甲基丁酰基) 托曼托甙元[20-O-(2-methylbutyryl)-tomentogenin]和二氢肉珊瑚甙元3-O-β-D-吡喃黄夹糖基(1-4)-β-D-吡喃夹竹桃糖基(1-4)-β-D-吡喃磁麻糖甙[dihydrosarcostin 3-O-β-D-thevetopyranosyl(1-4)-β-D-oleandropyranosyl(1-4)-β-D-cymaropyranoside]。     

陈旧性跟骨骨折截骨治疗40例

0　引言　陈旧性跟骨骨折晚期出现患足疼痛及跛行 ,功能障碍的病理变化十分复杂 ,治疗也较困难 .近年来我们应用跟骨截骨 ,距后关节融合 ,外踝管扩大术治疗该病 40例共 41足 ,获得满意效果 .1　对象和方法1.1　对象　陈旧性跟骨骨折患者 40例 41足 ;随访 37足 ;男36例 ,女 4例 ;年龄 2 0～ 5 7(平均 36 )岁 .左足 2 6例 ,右足 13例 ,双足 1例 .早期经保守治疗无效 34例 ,跟骨撬拔治疗术后过早负重 ,骨折部再次移位而出现症状 6例 7足 .41足均出现负重时距下关节周围弥漫性疼痛 ,跛行 ,患足跟部增宽 ,外翻畸形 6 9% ,内翻畸形 7% ,纵弓塌陷、…     

Candidate DNA replication initiation regions at human trinucleotide repeat disease loci

The positions of DNA replication initiation regions (IRs) at three human trinucleotide repeat (TNR) disease loci were examined in order to characterize the role played by IRs in explaining the known locus-specific variation in TNR instability levels. Using three different normal cell lines, candidate IRs were identified at the HD, SCA-7 and SBMA loci. At each locus the IR is less than 3.6 kb from the CAG/CTG repeat tract. Preliminary studies with a cell line homozygous for an HD disease mutation indicated no change in the position of the candidate IR in spite of the mutation. Comparison with experimental results from model systems suggests that a complex relationship may exist between instability and the proximity and/or orientation of the repeats with respect to an IR.     

Correlation of testicular sperm extraction with morphological, biophysical and endocrine profiles in men with azoospermia due to primary gonadal failure

To identify the predictive factors for testicular sperm extraction (TESE) and to understand the pathology associated with TESE, we carried out a prospective study in 40 consecutive men with azoospermia due to primary gonadal failure. The main outcome measure was the retrieval of at least one testicular spermatozoon. Endocrine and biophysical profiles, testicular histology, Johnsen score and testicular spermatids were used as predictors of sperm extraction. Spermatogenesis was quantified with the Johnsen score. A variable pattern of spermatogenesis was common, being present in 20 (50%) patients. Visualisation of testicular spermatids on testicular histology showed a strong association with TESE (P < 0.0001). Statistically significant differences were detected in plasma follicle stimulating hormone (FSH) and testicular volume between patients who had hypospermatogenesis and Sertoli cell-only or maturation arrest. There were no significant differences in Johnsen score, biophysical and endocrine profiles between the groups with successful and failed TESE. However, a statistically significant trend occurred with changes in histological pattern [chi2 for trend, P = 0.001; Pearson's coefficient (r) = 0.6], Johnsen score (P = 0.022; r = 0.5), testicular volume (P = 0.01; r = 0.5) and plasma FSH concentrations (P = 0.044; r = 0.4), albeit to a limited degree. Difference in the interpretation of histological patterns with different assessors was observed. The type of occupation or risk factors for azoospermia showed no association with testicular pathology or TESE. Variable histological patterns in different tubules in the same individual may explain the poor correlation of TESE with endocrine and biophysical profiles, Johnsen score and histological pattern. Differences in the amount of tissue used for TESE and histopathology, and misinterpretation of testicular histology rather than failure to quantify spermatogenesis may explain the poor correlation between histological patterns and TESE. Testicular spermatids predicted TESE. However, considerable overlap in values means that no single variable can provide a perfect discrimination between the groups with successful and failed TESE.      

Influence of ischaemia and reperfusion on cardiac signal transduction. G protein content, adenylyl cyclase activity, cyclic AMP content, and forskolin and dibutyryl cyclic AMP-induced inotropy in the rat Langendorff heart

Summary— We investigated whether post-receptor alterations contribute to the diminished β-adrenergic inotropic effects in the rat Langendorff heart following ischaemia (I) and reperfusion (R). We quantitated immunodetectable G_s and G_i protein α-subunit content, basal and stimulated adenylyl cyclase activity and cyclic AMP (cAMP) content in normoxic, ischaemic (30 min) and ischaemic reperfused (30 min) hearts. In addition, we measured the inotropic response of normoxic and reperfused Langendorff hearts to forskolin and dibutyryl cAMP (db-cAMP). Immunodetectable G_s and G_i α-subunits were unaltered by I or R. Basal adenylyl cyclase activity was decreased during I, but recovered during R. In membranes from normoxic hearts, isoprenaline, GTP, Gpp(NH)p, NaF, forskolin or Mn²⁺ enhanced adenylyl cyclase activity. This increase in activity was diminished in ischaemic hearts, but could be restored by R. cAMP content decreased time-dependently during I and did not recover by R, indicating ATP depletion. Forskolin and db-cAMP induced an inotropic response in normoxic hearts, which was virtually abolished after I and R. We conclude that adenylyl cyclase responsiveness is impaired during I. Since adenylyl cyclase responsiveness recovers during R, whereas inotropic responses to forskolin and db-cAMP are virtually absent in reperfused hearts, an additional mechanism downstream of cAMP formation appears to be defective during R, which prevents recovery of inotropic responses to hormonal stimulation.     

Three-phase radionuclide scintigraphy of the hand

Three-phase radionuclide scintigraphy of the hand was performed on 116 patients. Normal and abnormal patterns for radionuclide angiography, immediate post-injection blood-pool images, and delayed scans (3-4 hr.) were established. Of 80 patients with normal circulation, 61 (76%) had equal radial and ulnar artery flow bilaterally, while in 19 (24%) either the radial or ulnar artery was dominant. Abnormal studies were grouped into three categories: suspected vascular lesions (Group I), pain of uncertain etiology (Group II), and patients evaluated before and after reconstructive surgery (Group III). The diagnosis was correct in 89% of the patients in Group I (34/38), 89% of those in Group II (57/64), and all of those in Group III (14/14). Three-phase scintigraphy of the hand yields significant information about perfusion and bone metabolism.