Growth failure,risk of hospitalization and death for children with end-stage renal disease

Growth failure remains a significant problem for children with chronic renal insufficiency and end-stage renal disease (ESRD). We examined whether growth failure is associated with more-frequent hospitalizations or higher mortality in children with kidney disease. We studied data on prevalent United States pediatric patients with ESRD in 1990 who were followed through 1995. Patients were categorized according to the standard deviation score (SDS) of their incremental growth during 1990: severe (<–3 SDS), moderate growth failure (>–3 and <–2 SDS), and normal growth (>–2 SDS). Among 1,112 prevalent pediatric dialysis and transplant patients (<17 years, Tanner I–IV), those with severe and moderate growth failure had higher hospitalization rates {relative risk (RR) 1.14 [95% confidence interval (CI) 1.1, 1.2] and 1.24 [95% CI 1.2, 1.3]} respectively than those with normal growth after adjustment for age, gender, race, cause and duration of ESRD, and treatment modality (dialysis or transplant) in 1990. Kaplan-Meier survival analysis showed 5-year survival of 85% and 90% for patients with severe and moderate growth failure, respectively, compared with 96% for patients with normal growth (P<0.001, log-rank). Cox proportional hazards analysis revealed that those with severe (RR 2.9, 95% CI 1.6, 5.3) and moderate growth failure (RR 2.01, 95% CI 1.1, 3.6) had an increased risk of death compared with youths with normal growth, after adjustment. A higher proportion of deaths in the severe and moderate growth failure groups were attributed to infectious causes (22% and 18.7%, respectively) than in the normal growth group (15.6%). We conclude that growth failure is associated with a more-complicated clinical course and increased risk of death for children with kidney failure. Received: 15 August 2001 / Revised: 14 January 2002 / Accepted: 15 January 2002     

Combined use of platelet-rich plasma and autologous bone grafts in the treatment of long bone defects in mini-pigs

The use of platelet-rich plasma (PRP) for improving of bone defect healing is discussed controversially. The aim of this study was to assess the effect of PRP in combination with autologous cancellous graft on bone defect healing in a critical metaphyseal long bone defect. A critical size defect in the tibial metaphysis of 16 mini-pigs was filled either with autologous cancellous graft as control group or with autologous cancellous graft combined with autologous PRP. Compared to native blood platelets were enriched about 4.9-fold in the PRP. After 6 weeks, the specimens were assessed by X-ray and histological evaluation. Histomorphometrical analysis revealed that the area of new bone was significantly higher in the PRP group concerning the central area of the defect zone (p < 0.02) as well as the cortical defect zone (p < 0.01). All defects showed substantial new bone formation, but only defects of the PRP group regenerated entirely. The PRP group was superior to the control group even in the semi-quantitative assessment of the osseous bridging in both observed areas of the defect. Within the limits of the present study it could be demonstrated that PRP combined with autologous cancellous graft leads to a significantly better bone regeneration compared to isolated application of autologous cancellous graft in an in vivo critical size defect on load-bearing long bones of mini-pigs.     

Cigarette smoking decreases TGF-β1 serum concentrations after long bone fracture

TGF-β1 serum concentrations are considered to be one of the most promising markers of fracture healing. Previously, we demonstrated significant differences in the post-traumatic time courses of patients with timely and delayed fracture healing. The aim of this study was to evaluate possible differences in the serum concentrations of TGF-β1 in cigarette-smoking vs. non-smoking patients with timely and delayed fracture healing in order to understand pathophysiological pathways through which smoking impairs fracture healing.Serum samples were collected from 248 patients undergoing surgical treatment for long bone fractures within 1 year of surgery. Samples from 14 patients with atrophic-type delayed fracture healing were compared with 14 matched patients with normal bone healing. Each group included seven smokers and seven non-smokers. Post-operative serum concentrations were analysed at 1, 2, 4, 8, and 12 weeks as well as 1 year after surgery. The patients were monitored both clinically and radiologically for the entire duration of the study.All patients increased TGF-β1 serum concentrations after surgery. In patients with normal fracture healing, significantly higher TGF-β1 levels were observed in non-smokers (70 ng/ml) than in smokers (50 ng/ml) at the 4th week after surgery (p = 0.007). Also at the 4th week, in patients with delayed healing, significantly lower TGF-β1 levels were observed in smokers than in non-smokers (38 ng/ml vs. 47 ng/ml, p = 0.021). However, no significant differences between non-smokers with delayed healing and smokers with normal healing (p = 0.151) were observed at the 4th week after surgery. TGF-β1 serum concentrations reached a plateau in all groups from the 6th to the 12th week after surgery, with a slight decrease observed in the final measurement taken 1 year after surgery.This study demonstrates that, after fracture, TGF-β1 serum concentrations are reduced by smoking, and this reduction is statistically significant during the 4th week after surgery. Our findings may help reveal the mechanism by which smoking impairs fracture healing. Furthermore, these results may help to establish a serological marker that predicts impaired fracture healing soon after the injury. Surgeons will not only be able to monitor the bone healing, but they will also be able to monitor the success of additional treatments such as ultrasound and bone morphologic proteins (BMPs).     

结缔组织生长因子在椎间盘纤维化和退变中的表达和作用

目的研究疼痛椎间盘组织中结缔组织生长因子（connective tissue growth factor, CTGF）的表达及其在椎间盘纤维化和退变中的作用。方法收集腰椎后路融合过程中切除的43个疼痛的病理椎间盘，来自于28例行腰椎后路椎体间融合手术的严重椎间盘源性下腰痛患者；同时收集16个在MRIT2加权像信号强度明显减弱的无腰痛症状的退变椎间盘，取自于6例腰椎管狭窄症和8例多节段腰椎后路融合的患者（年龄44～75岁，平均53．5岁，男女比例为8：6）和8个正常对照椎间盘，来自于4具新鲜尸体标本（22～39岁，平均28岁）的L。和蛉．椎间盘。均行组织学检查并用免疫组化方法检测CTGF在不同椎间盘组织的表达。结果组织学检查发现，疼痛椎间盘组织显示不同程度的慢性血管化炎症反应。纤维环组织失去正常的胶原纤维板层结构，板层结构断裂、紊乱或相互交叉融合，正常的成纤维细胞被软骨细胞替代。髓核显示明显纤维化、血管浸润或形成炎性肉芽组织，软骨细胞被成纤维细胞所替代。免疫组化染色显示CTGF在疼痛椎间盘大量表达，无腰痛症状的退变椎间盘有少量表达，正常对照椎间盘没有表达。结论疼痛的退变椎间盘在组织学上明显不同于无腰痛症状的退变椎间盘。CTGF在疼痛椎间盘的大量表达可能与椎间盘纤维化和退变过程密切相关。     

Growth impairment shows an age-dependent pattern in boys with chronic kidney disease

The impact of chronological age on longitudinal body growth from early childhood through adolescence using detailed anthropometric methods has not yet been studied in children with chronic kidney disease (CKD). We have evaluated growth failure by measuring four components of linear growth: body height (HT), sitting height (SHT), arm length (AL) and leg length (LL). Data were prospectively collected for up to 7 years on 190 boys (3–21 years old) with congenital or hereditary CKD (all had developed at least stage 2 CKD by the age of 10 years). Patients showed the most severe growth failure in early childhood, followed by an acceleration in growth in pre-puberty, a slowing-down of growth at puberty, as expected, and thereafter a late speeding-up of growth until early adulthood. This pattern was observed irrespective of the degree of CKD and different treatment modalities, such as conservative treatment, recombinant human growth hormone (rhGH) therapy or transplantation. LL showed the most dynamic growth changes of all the parameters evaluated and emerged as the best indicator of statural growth in children with CKD. A specific age-dependent pattern of physical growth was identified in pediatric male CKD patients. This growth pattern should be considered in the evaluation of individual growth and the assessment of treatment efficacy such as rhGH therapy.     

Gender differences in the ratio between humerus width and length are established prior to puberty

Summary On a sample of 1,317 children aged 9.9 years we developed a novel method of measuring humeral dimensions from total body dual-energy X-ray absorptiometry (DXA) scans and showed that gender differences in the ratio between humeral width and length are established prior to puberty. Introduction It is recognised that long bone cross-sectional area is greater in males compared to females, which is thought to reflect more rapid periosteal bone growth in boys. However, it is currently unclear whether these findings reflect gender differences in bone size or shape. In the present study, we investigated whether gender differences exist in the balance between longitudinal and periosteal long bone growth in children, leading to gender differences in bone shape, based on a novel method for evaluating shape of the humerus. We also examined whether these differences are established prior to puberty. Methods Length, area and width of the humerus were estimated from total body DXA scans in 1,317 children aged 9.9 ± 0.33 years, who had participated in a nested case-control study of fractures within the Avon Longitudinal Study of Parents and Children (ALSPAC) (a geographically based birth cohort based in South West England). No differences were observed with respect to parameters of humeral geometry according to fracture history, and so both groups were pooled for further analysis. Aspect ratio (AR) of the humerus was calculated as humeral width divided by length. Total body height and weight were measured at the same time as the DXA scan. Puberty was assessed using self-completion questionnaires. Results Humeral width and length were positively associated with age and height in boys and girls combined (P < 0.001), and with Tanner stage in girls (P < 0.002). In contrast, age, height and Tanner stage were not related to humeral AR. We then examined gender differences in humeral shape according to pubertal stage. In prepubertal children (i.e. Tanner stage 1), humeral length was similar in boys and girls, but width (1.92 vs 1.88 cm, P < 0.001) and area (47.7 vs 46.9 cm², P < 0.001) were greater in boys, resulting in a greater AR (7.78 vs 7.53, P < 0.001). Similar gender differences were observed in early pubertal children (i.e. Tanner stage 2). Conclusion We conclude that the greater periosteal diameter of boys compared to girls reflects differences in the balance between longitudinal and periosteal bone growth. Interestingly, resulting gender differences in humeral AR are established in prepubertal children.     

Adult height of three renal transplant patients after growth hormone therapy

Three girls with normal growth hormone secretion had received renal transplantation when aged 2 to 6 years. They had had severely retarded growth (SD for height score was −7.4 to −3.7) at the time of transplantation. After renal transplantation, steroid was withdrawn and they were treated with recombinant human growth hormone; they subsequently reached adult heights of 145 to 156 cm. The SD for adult height score was −2.6 to −0.3. The adult height in two patients was over their target height, calculated using the mean of the parents’ height. This report shows the efficacy of steroid withdrawal and recombinant human growth hormone therapy in achieving adult height in these three girls after renal transplantation.     

住院精神分裂症患者主观舒适度的影响因素分析

目的 了解影响精神分裂症患者主观舒适度的相关因素。方法 对200例住院精神分裂症患者测评“抗精神病药物治疗中主观舒适度（SWN）简表”及自制的“相关因素调查表”。结果 住院精神分裂症患者SWN评分异常率为31％,SWN评分异常组与正常组相比,在总病程、住院次数、服药次数、药物剂量、家庭经济水平、服药依从性、社会支持、医患关系、诊断亚型、合并使用抗副作用药、藏药行为等方面差异显著。2项Logistic回归分析显示,精神分裂症患者主观舒适度影响因素依次为：药物剂量、合并使用抗副作用药、服药依从性、藏药行为、家庭经济水平、医患关系。结论 在治疗精神分裂症患者时应注意多因素对主观舒适度的影响,尤其注意发挥人为干预因素作用。     

体外诱导BMSCs向软骨分化的方法研究进展

目的全面了解目前体外诱导BMSCs向软骨分化的方法,为软骨组织工程研究提供参考。方法广泛查阅近年来有关软骨组织工程中诱导BMSCs向软骨分化的文献,并进行综合分析。结果目前BMSCs诱导成软骨方法主要是添加外源性生长因子,其中TGF-β家族被公认为最重要的诱导和调节因子。其他重要的诱导方法包括添加多种化学因子、物理因素、转基因技术和微环境诱导等方法,但这些方法仍存在诱导效率低、诱导效果不稳定的问题。结论诱导方法的进展促进了BMSCs在软骨组织工程中的应用,建立更高效、简便、安全的诱导方法仍是软骨组织工程领域重要研究课题之一。