Legal framework conditions for the reprocessing of medical devices

The processing of single-use products is permissible pursuant to medical device law. This is apparent both from the wording of the German Law on Medical Devices and from the purpose and the objectives underpinning the legislative materials. The prerequisite for processing is, however, compliance with the the Joint Recommendation of the Commission for Hospital Hygiene and the Prevention of Infection at the Robert Koch Institute (RKI) and the Federal Institute for Drugs and Medical Products (BfArM).For medical devices in the category “critical C”, the RKI/BfArM-recommendation provides that the processor’s quality management system must be certified by a body accredited by the Central Authority of the Federal States for Health Protection with regard to Medicinal Products and Medical Devices (Zentralstelle der Länder für Gesundheitsschutz bei Arzneimitteln und Medizinprodukten, ZLG). The certification must be carried out in accordance with EN ISO 13485:2003+AC:2007.On April 4, 2008 the Federal Health Ministry (Bundesministerium für Gesundheit, BMG) presented a progress report on the processing of medical devices. The BMG concludes that the legal framework for the processing of medical devices is sufficient, and that a prohibition on the processing of single-use products is inappropriate.     

Assessing the relative importance of the biophysical properties of amino acid substitutions associated with human genetic disease

The inclusion of a mutation in a pathology-based database such as the Human Gene Mutation Database (HGMD) is a two-stage process: first, the mutation must occur at the DNA level, then it must cause a clinically detectable disease state. The likelihood of the latter step, termed the relative clinical observation likelihood (RCOL), can be regarded as a function of the structural/functional consequences of a mutation at the protein level. Following this paradigm, we modeled in silico all amino acid replacements that could potentially have arisen from an inherited single base pair substitution in five human genes encoding arylsulphatase A (ARSA), antithrombin III (SERPINC1), protein C (PROC), phenylalanine hydroxylase (PAH), and transthyretin (TTR). These proteins were chosen on the basis of 1) the availability of a crystallographic structure, and 2) a sufficiently large number of amino acid replacements being logged in HGMD. A total of 9,795 possible mutant structures were modeled and 20 different biophysical parameters assessed. Together with the HGMD-derived spectra of clinically detected mutations, these data allowed maximum likelihood estimation of RCOL profiles for the 20 parameters studied. Nine parameters (including energy difference between wild-type and mutant structures, accessibility of the mutated residue, and distance from the binding/active site) exhibited statistically significant variability in their RCOL profiles, indicating that mutation-associated changes affected protein function. As yet, however, a biological meaning could only be attributed to the RCOL profiles of solvent accessibility and, for three proteins, local energy change, disturbed geometry, and distance from the active center. The limited ability of the biophysical properties of mutations to explain clinical consequences is probably due to our current lack of understanding as to which amino acid residues are critical for protein folding. However, since the proteins examined here were unrelated, and our findings consistent, it may nevertheless prove possible to extrapolate to other proteins whose dysfunction underlies inherited disease.     

Consensus on infertility treatment related to polycystic ovary syndrome

The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. On the basis of the currently available evidence, a group of experts reached a consensus regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counseling should be provided emphasizing the importance of lifestyle, especially weight reduction and exercise in overweight women, smoking, and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotropins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotropins is associated with increased chances for multiple pregnancy, and, therefore, intense monitoring of ovarian response is required. Laparoscopic ovarian surgery alone is usually effective in less than 50% of women, and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC-gonadotropin paradigm) is reported to be highly effective with a cumulative singleton live-birth rate of 72%. Recommended third-line treatment is in vitro fertilization (IVF). More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-line, second-line, or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.     

Effects of intermittent hypoxia on SaO2, cerebral and muscle oxygenation during maximal exercise in athletes with exercise-induced hypoxemia

In a placebo-controlled study, the effects of intermittent hypoxic exposures (IHE) or a placebo control for 10 days, were examined on the extent of exercise-induced hypoxemia (EIH), cerebral and muscle oxygenation (near-infrared spectroscopy) and [Formula: see text] Eight athletes who had previously displayed EIH (fall in saturation of arterial oxygen (SaO(2)) of >4% from rest) during an incremental maximal exercise test, volunteered for the present research. Prior to (baseline), and 2 days following (post) the IHE or placebo, an incremental maximal exercise test was performed whilst SaO(2), heart rate, cerebral and muscle oxygenation and respiratory gas exchange were measured continuously. After IHE, but not placebo, EIH was less pronounced at [Formula: see text] (IHE group, SaO(2) at [Formula: see text] baseline 91.23 +/- 1.10%, post 94.10 +/- 2.19%; P < 0.01, mean +/- SD). This reduction was reflected in an increased ventilation (NS), a lower end-tidal CO(2) (P < 0.01), and lowered cerebral TOI during heavy exercise [Formula: see text] Conversely, muscle tHb at maximal exercise, was increased (2.4 +/- 1.8 DeltamuM, P = 0.01, mean +/- 95 CL) following IHE, whilst de-oxygenated Hb at 90% of [Formula: see text] was reduced (-0.9 +/- 0.8 DeltamuM, P = 0.02). These data indicate that exposure to IHE can attenuate the degree of EIH. Despite a potential compromise in cerebral oxygenation, exposure to IHE may induce some positive physiological adaptations at the muscle tissue level. We speculate that the unchanged [Formula: see text] following IHE might reflect a balance between these central (cerebral) and peripheral (muscle) adaptations.     

Transthyretin mutations in hyperthyroxinemia and amyloid diseases

Over 80 different disease-causing mutations in transthyretin (TTR) have been reported. The vast majority are inherited in an autosomal dominant manner and are related to amyloid deposition, affecting predominantly peripheral nerve and/or the heart. A small portion of TTR mutations are apparently non-amyloidogenic. Among these are mutations responsible for hyperthyroxinemia, presenting high affinity for thyroxine (a TTR ligand). Compound heterozygotic individuals for TTR mutants have been described; noteworthy is the clinically protective effect exerted by a non-pathogenic over a pathogenic mutation. Current TTR mutations and their significance are briefly reviewed here.     

2007-2012年四川省包虫病流行区网络直报疫情分析

目的根据网络直报系统信息分析四川省人群棘球蚴病（包虫病）的发病情况及其流行病学特点,为优化本病控制措施提供科学依据。方法通过中国疾病预防控制信息（即网络直报）系统2007～2012年上报的四川省包虫病病例,用SPSS18．0和Excel2010进行数据统计分析,对该病疫情进行描述性流行病学分析。结果2007～2012年四川省包虫病累计报告10037例,年平均患病率为55．91／10万;从年龄分布看,包虫病发病主要集中在25～65岁人群,呈现中间高两头低的现象（χ2=4544．23,P〈0．01）;从性别分布看,包虫病患者中男女性别比例为1：22（χ2=49．12,P〈0．05）;从职业分布看,牧民所占比例最大,为84．64％（χ2=5841．57,P〈0．01）;从地区分布看,包虫病患者主要分布于甘孜州（9127例）和阿坝州（807例）。结论四川省包虫病流行的风险因素依然存在,包虫病流行状况未得到明显改善,因此应继续加大本病的防控力度并探索更有效的防控措施。     

Kanechlor 500‐mediated changes in serum and hepatic thyroxine levels primarily occur in a transthyretin‐unrelated manner

The effects of Kanechlor‐500 (KC500) on the levels of serum total thyroxine (T₄) and hepatic T₄ in wild‐type C57BL/6 (WT) and its transthyretin (TTR)‐deficient (TTR‐null) mice were comparatively examined. Four days after a single intraperitoneal injection with KC500 (100 mg/kg body weight), serum total T₄ levels were significantly decreased in both WT and TTR‐null mice. The KC500 pretreatment also promoted serum [¹²⁵I]T₄ clearance in both strains of mice administrated with [¹²⁵I]T₄, and the promotion of serum [¹²⁵I]T₄ clearance in WT mice occurred without inhibition of the [¹²⁵I]T₄‐TTR complex formation. Furthermore, the KC500 pretreatment led to significant increases in liver weight, steady‐state distribution volume of [¹²⁵I]T₄, hepatic accumulation level of [¹²⁵I]T₄, and concentration ratio of the liver to serum in both strains of mice. The present findings indicate that the KC500‐mediated decrease in serum T₄ level occurs in a TTR‐unrelated manner and further suggest that KC500‐promoted T₄ accumulation in the liver occurs through the development of liver hypertrophy and the promotion of T₄ transportation from serum to liver.     

甲状腺素运载蛋白时间分辨免疫荧光试剂盒的制备和效能评价

目的制备甲状腺素运载蛋白(transthyretin,TTR)的时间分辨免疫荧光(time-resolved fluoroimmunoassay,TRFIA)试剂盒并对其性能进行评价。方法将抗TTR的4H2单克隆抗体作为包被抗体包被至96孔板,用Eu^3+标记3E4单克隆抗体作为检测抗体,制备双抗体夹心TRFIA试剂盒,应用该试剂盒对42例川崎病(Kawasaki disease,KD)患儿及13名健康儿童的血清进行检测,以稀释回收率、准确度、精密度、稳定性等指标对试剂盒的效能进行评价。结果该研究制备的TTR TRFIA试剂盒与Western blot法同时检测42份KD临床样本和13份健康样本,两方法的结果符合率为100%,特异性强。试剂盒的最低检出浓度为0.05μg/ml,稀释回收率为88.00%~111.00%,分析内精密度为8.01%~9.17%,分析间精密度为8.88%~11.82%。稳定性实验表明该试剂盒可在4℃稳定保存6个月,37℃稳定保存7 d。结论该研究制备的TTR TRFIA试剂盒具有准确性高、方便快捷等优点,适用于大批量临床KD血清样品的TTR检测,为快速区分丙种球蛋白敏感型和无反应型的KD患儿提供了方法。