Aspects of the treatment of Turner syndrome

Several issues have to be considered when taking care of girls and women with Turner syndrome. During childhood, short stature is the primary concern and treatment with growth hormone (GH) is now widely used, often in conjunction with the androgen, oxandrolone. Recent studies indicate that doses used previously in the treatment of short stature have been too small. Induction of puberty should be performed at an appropriate age with reference to the peers of the patient. In adulthood, female sex hormone substitution should be offered to possibly prevent the increased morbidity seen in Turner syndrome, which consists of increased risk of fractures and osteoporosis, a clustering of diseases like ischaemic heart disease, hypertension, stroke and Type 2 diabetes, the latter entities being involved in the insulin resistance syndrome. Furthermore, hypothyreosis are often seen and the risk of Type 1 diabetes may also be increased. Congenital malformations of the heart are frequently seen in Turner syndrome, possibly increasing the risk of dissecting aorta aneurism. Liver enzymes are often elevated in Turner syndrome and there may be an increased risk of cirrhosis of the liver. Mortality does seem to be increased in Turner syndrome and women with the ‘pure’ 45,X karyotype do seem to be most severely affected. In the clinical practice of Turner syndrome, a careful monitoring of glucose and bone metabolism, weight, thyroid function and blood pressure should be performed. A cardiovascular risk profile should be determined and the patient informed concerning risks and benefits from sex hormone replacement therapy. Based on the available literature, sex hormone replacement therapy is highly recommended, although at present there are no longitudinal data documenting the long-term positive effect of sex steroid substitution. However, hypogonadism is expected to explain at least part of the decreased lifespan found in Turner syndrome. Since general physicians encounter Turner patients infrequently, it is recommended that the care and treatment of Turner syndrome is centralised.     

Differences of height and body mass index of youths in urban vs rural areas in Hunan province of China

Background: Economic reforms in China were implemented approximately 30 years ago. Since then, people's nutrition, living conditions and overall health have continually improved, but there has been an imbalance between the progresses in urban vs rural areas. Height and body mass index (BMI) are regarded as two important indicators of nutritional status and overall health.

Aim: The aim of this study was to investigate differences in height and BMI between Chinese youths of rural vs urban areas and further, to determine whether these differences have changed over time (1990s vs 2000s).

Subject and methods: 24 194 urban youths and 7130 rural youths were recruited in Hunan province of China. In each gender group, the subjects were divided into eight subsets according to age, geographic area residence, and decade when the youths were measured. Independent t-tests were used to test the differences of height and BMI between the studied groups.

Results: Both male and female youths from urban areas were significantly taller than youths from rural areas in both the 1990s and 2000s (all p<0.001), with the exception of the 1990s female 15–18 years subset (p=0.21). The height of youths was significantly greater in the 2000s compared to the corresponding gender and geographic subset in the 1990s (p<0.001), except for the female 15–18 years subset from rural areas (p=0.10). Similar results were obtained for BMI.

Conclusion: There are significant differences in height and BMI between youths raised in urban vs rural areas, and positive growth trends of height and BMI over time (1990s vs 2000s) in youths in Hunan Province of China.     

膝关节固定后髌骨腱的生物力学改变

背景：骨关节固定常作为防止受伤组织被再次损伤的方法。 目的：膝关节固定对兔髌骨腱力学特性及超微形态的影响。 方法：将20只成年兔等分为固定组和对照组。固定组兔左后肢通过石膏和2个可调铝夹板，保持膝伸直，踝关节屈曲90°，固定6周后，取髌骨腱-骨复合物，观察两组髌骨腱的生物力学性能和超微结构变化。 结果与结论：膝关节固定6周拉伸强度和切线模量分别下降至对照组的64.44%和53.08%(P < 0.01)，但两组伸长率和最大负荷差异没有显著性意义。两组材料常数及应力应变关系曲线完全不同。固定组髌骨腱的横截面积明显大于对照组(P < 0.01)，小胶原纤维占有优势。说明固定不仅会导致髌骨腱生物力学的变化，而且对髌骨腱自身也产生影响。     

浅析平原型生活垃圾填埋场工艺设计

针对平原型生活垃圾填埋场的设计,以浙江省嘉善县生活垃圾填埋场二期工程为例,从地下水位、地基承载力、土方平衡等方面介绍了库区基底高程、环库区垃圾堤坝顶高程、垃圾堆体顶高程这3个关键参数的确定过程.     

Childhood growth and age at diagnosis with Type 1 diabetes in Colorado young people

Objective Studies have suggested that the age at diagnosis of Type 1 diabetes (T1D) is decreasing over time. The overload hypothesis postulates that risk factors, such as accelerated growth, may be responsible for this decrease. We assessed changes in age, body mass index (BMI), weight and height at diagnosis with T1D in non‐Hispanic white (NHW) and Hispanic (HISP) young people from Colorado, using data from the IDDM Registry and SEARCH Study. Methods In three time periods, 656 (1978–1983), 562 (1984–1988) and 712 (2002–2004) young people aged 2–17 years were newly diagnosed with T1D. Age, weight, height and presence of diabetic ketoacidosis (DKA) at diagnosis with T1D were obtained from medical records. Trends over the three time periods were assessed with regression analyses. Results Age at diagnosis decreased by 9.6 months over time (P = 0.0002). Mean BMI standard deviation score (SDS), weight SDS and height SDS increased over time (P < 0.0001), while prevalence of DKA decreased (P < 0.0001). Increasing height over time accounted for 15% (P = 0.04) of the decreasing age at diagnosis with T1D. Conclusions Our study provides evidence that increased linear growth, but not increased BMI or weight over time, may account, at least in part, for the younger age at diagnosis of T1D in Colorado children. This finding supports the hypothesis that increasing environmental pressure resulting from changes in potentially preventable risk factors may accelerate the onset of T1D in children.     

2型糖尿病患者体脂指标与血压血脂的关系

目的：探讨2型糖尿病患者体质指数（BMI）、腰围（WC）、腰臀比（WHR）、腰围／身高比（WHtR）与血压、血脂的关系。方法调查191例2型糖尿病患者,测量身高、体重、腰围、臀围及血压,计算BMI、WHR、WHtR,测定总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）,分析上述四种体脂指标与2型糖尿病患者血压、血脂的关系。结果偏相关分析显示：BMI、WC、WHR、WHtR均与收缩压（SBP）独立正相关,其中WHtR相关性最强。BMI、WHtR均与舒张压（DBP）呈正相关。BMI、WC、WHR、WHtR异常组的SBP、DBP、TC、TG、LDL-C水平均较正常组偏高,HDL-C水平较正常组偏低。多元逐步线性回归表示WHtR为TG水平的影响因素。结论各体脂指标（BMI、WC、WHR、WHtR）与2型糖尿病患者的血压及血脂水平的改变有一定的相关性,对于减少2型糖尿病患者发生代谢综合征的风险而言,预防肥胖是至关重要的。     

贵州地区汉族人群GDF5基因单核苷酸多态性与成人终身高的关系

目的 探讨生长分化因子5(GDF5)基因rs143383、rs143384、rs6060369和rs224331位点单核苷酸多态性(SNPs)与贵州地区汉族人群成人终身高的相关性.方法 对贵州地区1 069例汉族健康体检者进行体格检查及问卷调查,收集抗凝血标本并提取DNA.用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)方法检测GDF5基因的SNPs,并分析其与身高的相关性.结果 成年女性中,GDF5基因rs143383、rs143384、rs6060369和rs224331基因型分布可分别解释身高变异的1.4％、0.9％、1.1％和1.0％(P＜0.05);在GDF5基因rs143383和rs143384位点,携带GG基因型的个体平均身高均为最高,分别比AG和AA基因型个体高1.7 cm (P＜0.01)、2.3 cm (P＜0.05)和1.6 cm (P＜0.05)、2.1 cm(P＜0.01);在GDF5基因rs6060369位点,携带CC基因型的个体平均身高分别比CT和TT基因型个体高1.7 cm (P＜0.05)和2.2 cm (P＜0.01).但是在成年男性中未发现GDF5基因上述SNPs位点与身高的相关性.结论 GDF5基因单核苷酸多态性与贵州地区成年汉族女性身高有关,GDF5基因可能是影响中国汉族成人女性身高个体差异的基因.     

Subclinical nerve dysfunction in children and adolescents with IDDM

Summary The purpose of this study was to investigate whether young insulin-dependent diabetic patients still develop peripheral nerve dysfunction when using modern multiple insulin injection therapy and to elucidate if this correlated with various disease parameters. Seventy-five patients, 7 to 20 years old with a duration of diabetes of more than 3 years, and 128 age-matched healthy control subjects underwent bilateral studies of median, peroneal, and sural nerves. Presence of diabetes lowered motor conduction velocity (p<0.0001), sensory conduction velocity (p<0.0001) and sensory nerve action potential (p<0.05) in all examined nerves. The mean change in conduction velocity induced by diabetes was –4.8 m/s in the peroneal nerve, –3.3 m/s in the median motor nerve, –2.6 m/s in the sural nerve and –2.4 m/s in the median sensory nerve. Fifty-seven percent of the patients had abnormal conduction (values outside 95% predictive interval) which was seen most often in the motor nerves, especially in the peroneal nerve (41%) followed by the median nerve (24%). In multiple regression analysis, long-term poor metabolic control and increased body length correlated with nerve dysfunction identified in most examined parameters. Three patients had signs or symptoms suggestive of neuropathy. It is concluded that despite modern multiple insulin injection therapy, with reasonably good metabolic control, nerve dysfunction is still common in children and adolescents with insulin-dependent diabetes mellitus. Risk factors are increased height and long-term poor metabolic control.Abbreviations IDDM Insulin-dependent diabetes mellitus - MIT multiple insulin injection therapy - MCV motor nerve conduction velocity - CMAP compound muscle action potential - DML distal motor latency - SCV sensory nerve conduction velocity - SNAP sensory nerve action potential     

Mast cell degranulation during abdominal surgery initiates postoperative ileus in mice

BACKGROUND & AIMS: Inflammation of the intestinal muscularis following manipulation during surgery plays a crucial role in the pathogenesis of postoperative ileus. Here, we evaluate the role of mast cell activation in the recruitment of infiltrates in a murine model. METHODS: Twenty-four hours after control laparotomy or intestinal manipulation, gastric emptying was determined. Mast cell degranulation was determined by measurement of mast cell protease-I in peritoneal fluid. Intestinal inflammation was assessed by determination of tissue myeloperoxidase activity and histochemical staining. RESULTS: Intestinal manipulation elicited a significant increase in mast cell protease-I levels in peritoneal fluid and resulted in recruitment of inflammatory infiltrates to the intestinal muscularis. This infiltrate was associated with a delay in gastric emptying 24 hours after surgery. Pretreatment with mast cell stabilizers ketotifen (1 mg/kg, p.o.) or doxantrazole (5 mg/kg, i.p.) prevented both manipulation-induced inflammation and gastroparesis. Reciprocally, in vivo exposure of an ileal loop to the mast cell secretagogue compound 48/80 (0.2 mg/mL for 1 minute) induced muscular inflammation and delayed gastric emptying. The manipulation-induced inflammation was dependent on the presence of mast cells because intestinal manipulation in mast cell-deficient Kit/Kitv mice did not elicit significant leukocyte recruitment. Reconstitution of Kit/Kitv mice with cultured bone marrow-derived mast cells from congenic wild types restored the manipulation-induced inflammation. CONCLUSIONS: Our results show that degranulation of connective tissue mast cells is a key event for the establishment of the intestinal infiltrate that mediates postoperative ileus following abdominal surgery.     

The many weak instruments problem and Mendelian randomization

Instrumental variable estimates of causal effects can be biased when using many instruments that are only weakly associated with the exposure. We describe several techniques to reduce this bias and estimate corrected standard errors. We present our findings using a simulation study and an empirical application. For the latter, we estimate the effect of height on lung function, using genetic variants as instruments for height. Our simulation study demonstrates that, using many weak individual variants, two‐stage least squares (2SLS) is biased, whereas the limited information maximum likelihood (LIML) and the continuously updating estimator (CUE) are unbiased and have accurate rejection frequencies when standard errors are corrected for the presence of many weak instruments. Our illustrative empirical example uses data on 3631 children from England. We used 180 genetic variants as instruments and compared conventional ordinary least squares estimates with results for the 2SLS, LIML, and CUE instrumental variable estimators using the individual height variants. We further compare these with instrumental variable estimates using an unweighted or weighted allele score as single instruments. In conclusion, the allele scores and CUE gave consistent estimates of the causal effect. In our empirical example, estimates using the allele score were more efficient. CUE with corrected standard errors, however, provides a useful additional statistical tool in applications with many weak instruments. The CUE may be preferred over an allele score if the population weights for the allele score are unknown or when the causal effects of multiple risk factors are estimated jointly. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.