Relations between age, metabolic control, disease adjustment and psychological aspects in insulin-dependent diabetes mellitus

The relations between age, metabolic control, disease adjustment, and psychological factors in boys and girls with recently diagnosed insulin-dependent diabetes mellitus (IDDM) were studied. Older girls had significant higher postremission glycosylated haemoglobin A (Hb A_lc) levels ( p = 0.008). Girls with more hospitalizations had a lower developmental level ( p = 0.05), and had significantly more problems in the behavioural rating ( p = 0.05). Boys with more hospitalizations had a more external locus of control ( p = 0.01), more difficulties with disease adjustment, more emotional problems, and were also clinically assessed as having more behavioural problems. Boys showing more difficulties in psychological adjustment to the disease also had higher postremission Hb A_1clevels ( p = 0.02). Although Swedish children with IDDM of short disease duration do not differ from healthy children in important psychological aspects, older girls and a small group of problematic younger boys are at risk of developing metabolic imbalance after a short disease duration.     

Metabolic effects of growth hormone treatment: an early predictor of growth response?

Fourteen children receiving one year of recombinant human growth hormone (rhGH) treatment underwent measurement of serial changes in body composition (measured by skinfold thickness, bioelectrical impedance, and H2(18)O dilution), resting energy expenditure (REE, estimated by ventilated hood indirect calorimetry), and total free living daily energy expenditure (TEE, measured by the doubly labelled water technique). Mean height velocity increased from 4.9 to 8.6 cm/year after six months of treatment. Fat free mass (FFM) increased more during the first six weeks (24.4 g/day) than from six to 26 weeks of treatment (6.8 g/day); fat mass decreased by 7.2 g/day and 1.1 g/day respectively. The six week increase in REE (kJ/day) was maintained after six months of treatment, though expressed per kilogram FFM (kJ/kgFFM/day), returned to pretreatment values by three months. Height velocity increases at six months correlated with six week changes in fat mass measured by skinfold thickness and REE, though use of this relationship to predict growth response in individuals is limited by the wide 95% prediction intervals. No significant changes in growth, body composition, or energy expenditure were observed between six and 12 months of treatment, in either patients who had initially responded well to treatment or those who were poor initial responders to treatment and who had their dose of rhGH doubled after six months.     

HIV-1tat induced apoptosis of T-cells is not mediated by TGF-β

Recent reports have demonstrated that the HIV-1 transactivator protein,tat, induces apoptosis in T-lymphocyte cell lines, as well as in peripheral blood mononuclear cells, and stimulates a cascade of events resulting in up-regulation of the potent immunosuppressive cytokine, transforming growth factor-β (TGF-β). In this study we evaluated the ability of TGF-β to mediatetat induced apoptosis in T-lymphocyte cell lines. T-cells treated exogenously with either TGF-β1 or a combination of tat and pan-specific TGF-β neutralizing antibodies showed little change in the amount of apoptosis. When treated with pan-specific TGF-β neutralizing antibodies, Jurkat cells that stably expresstat protein (Jurkat-tat) showed only a modest decrease in apoptosis, while CEM-TART cells (CEM T-cells expressing both HIV-1tat andrev) demonstrated little change in the amount of apoptosis. In conclusion, we have demonstrated that TGF-β does not play a significant role in mediatingtat induced T-cell apoptosis.     

Intraventricular haemorrhage in the preterm infant without hyaline membrane disease

The clinicopathological associations of 33 singleton infants who died with intraventricular haemorrhage (IVH) without hyaline membrane disease (HMD) ('IVH only') were compared with those of 39 infants who died with IVH+HMD over the same gestation range in order to determine what factors other than those related to HMD may contribute to the pathogenesis of IVH. The incidence of 'IVH only' was inversely related to gestational age in the Hammersmith birth population, whereas the incidence of IVH+HMD rose to a peak at 28-29 weeks' gestation. Infants with 'IVH only' lived longer on average than those with IVH+HMD despite a lower birthweight and shorter gestation. Infants who died in the first 12 hours from 'IVH only' had suffered severe birth asphyxia but in those who died later the main symptom was recurrent apnoea. Fewer infants with asphyxia but in those who died later the main symptom was.recurrent apnoea. Fewer infants with 'IVH only' were given alkali therapy or were connected to the ventilator as compared to those with IVH+HMD, but there were no differences in alkali therapy in those who lived for 12 hours or more. In the 'IVH only' group there was a high incidence of haemorrhage from other sites and of bacterial infections. It is suggested that, in the absence of HMD, extreme immaturity is the main factor determining the occurrence of IVH. Birth asphyxia, apnoeic attacks, haemorrhage, and infections may play subsidiary roles, possibly through development of metabolic acidosis.     

超长段尿道狭窄术后勃起功能的评估

目的 探讨自体组织替代治疗超长段尿道狭窄对勃起功能的影响.方法 回顾性分析2007年1月至2009年1月采用不同自体组织补片(阴囊纵隔、包皮内板、口腔黏膜)Onlay术式替代治疗超长段男性尿道狭窄患者的临床资料,并随访患者ⅡEF-5评分、QOL评分及最大尿流率,并与术前相应情况进行分析.结果 根据研究标准收集23份有效数据.患者术前及术后3、6、12个月QOL评分分别为5.22±0.75、1.22±1.40、1.82±1.17、2.07±0.46,最大尿流率分别为(3.93±3.62)、(22.46±4.65)、(23.81±6.22)、(21.52±7.44)ml/s,术后不同时期均较术前明显改善(P＜0.01).术前及术后3、6、12个月ⅡEF-5评分分别为14.47±9.55、14.70±5.32、14.26±3.29和14.58±3.62,组间比较差异无统计学意义(P＞0.05).9例狭窄部位累及至后尿道者术后3、6、12个月ⅡEF-5评分分别为11.67±2.59、12.35±1.83、13.19±1.67,14例单纯前尿道狭窄者分别为17.79±6.42、16.57±4.78、16.01±3.85,2组间比较差异均有统计学意义(P＜0.05).狭窄累及后尿道患者多元线性回归分析中,年龄、受伤时间及尿道狭窄段长度与替代术后ⅡEF-5评分呈多元线性相关.结论 自体组织替代治疗男性超长段尿道狭窄对勃起功能影响不明显;狭窄段累及后尿道时可能对患者勃起功能产生一定影响.患者年龄和受伤时间对勃起功能有协同影响作用.

Abstract：

Objective To investigate the effect of substitutive reconstruction of long urethral stricture on male erectile function. Methods From January 2007 to January 2009, 23 patients with anterior or posterior long urethral stricture were accepted for a variety of onlay substitutive procedures, including lingual mucosa, perputial skin, and mid-scrotal skin. During the follow-up, data from the International Index of Erectile Function-5 (ⅡEF-5) questionnaire and the Quality of Life (QOL) questionnaire as well as maximal flow rate were recorded. All data were compared with those obtained before surgery. Results Significant improvement in QOL (1.22 ± 1.40, 1.82 ± 1. 17,2.07± 0.46) and maximal flow rate (22.46± 4.65, 23.81 ± 6.22, 21.52 ±7.44 ) could be observed 3, 6 and 12 months after surgery compared with those before surgery (5. 22 ± 0. 75, 3. 93 ± 3. 62)(P＜0.01). No significant differences in the responses to the ⅡEF-5 questionnaire were observed among all patients during the follow-up (P＞0. 05). At the 3, 6 and 12 months after procedure,scores of ⅡEF-5 in patients with anterior urethral stricture ( 17.79 ± 6.42, 16. 57 ± 4. 78, 16.01 ±3.85) were significantly higher than those with posterior urethral stricture (11.67 ± 2.59, 12.35 ±1.83,13. 19±1.67, P＜0.05). In patients with posterior urethral stricture, the multiple linear regression showed that age, time interval of injury and length of stricture were related to the ⅡEF-5score (P＜0.05). Conclusions Substitutive reconstruction for treating the long urethral stricture has little effect on male erectile function. But the location of stricture, especially extended to posterior urethra, may have impact on the erectile function.     

On optimal gene-based analysis of genome scans

Univariate analysis of markers has modest power when there are multiple causal variants within a gene. Under this scenario, combining the effects of all variants from a gene in a gene-wide statistic is thought to increase power. However, it is not really clear (1) what is the performance of most commonly used gene-wide methods for whole genome scans and (2) how scalable these methods are for more computationally intensive analyses, e.g. analysis of genome-wide sequence data. We attempt to answer these questions by using realistic simulations to assess the performance of a range of gene-based methods: (1) commonly used, e.g. VEGAS and GATES; (2) less commonly used, e.g. Simes, adaptive sum (aSUM), and kernel methods; and (3) a combination of univariate and multivariate tests we proposed for the analysis of markers in linkage disequilibrium. Simes is the fastest method and has good power for single causal variant models. aSUM method has good power for multiple causal variant models, especially at lower gene lengths. Our proposed statistic yields good power for all causal models. Given the extreme data volumes coming from sequencing studies, we recommend a two step analysis of genome scans. The initial step uses the very fast Simes procedure to flag possibly interesting genes. The second step refines interesting signals by using more computationally intensive methods, e.g. (1) aSUM for shorter and (2) VEGAS for larger gene lengths. Alternatively, genome scans can be analyzed using only our proposed method while sacrificing only a modest amount of power.     

Comparison of association methods for dense marker data

While data sets based on dense genome scans are becoming increasingly common, there are many theoretical questions that remain unanswered. How can a large number of markers in high linkage disequilibrium (LD) and rare disease variants be simulated efficiently? How should markers in high LD be analyzed: individually or jointly? Are there fast and simple methods to adjust for correlation of tests? What is the power penalty for conservative Bonferroni adjustments? Assuming that association scans are adequately powered, we attempt to answer these questions. Performance of single‐point and multipoint tests, and their hybrids, is investigated using two simulation designs. The first simulation design uses theoretically derived LD patterns. The second design uses LD patterns based on real data. For the theoretical simulations we used polychoric correlation as a measure of LD to facilitate simulation of markers in LD and rare disease variants. Based on the simulation results of the two studies, we conclude that statistical tests assuming only additive genotype effects (i.e. Armitage and especially multipoint T²) should be used cautiously due to their suboptimal power in certain settings. A false discovery rate (FDR)‐adjusted combination of tests for additive, dominant and recessive effects had close to optimal power. However, the common genotypic χ² test performed adequately and could be used in lieu of the FDR combination. While some hybrid methods yield (sometimes spectacularly) higher power they are computationally intensive. We also propose an “exact” method to adjust for multiple testing, which yields nominally higher power than the Bonferroni correction. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.