Why do studies show different associations between intrauterine exposure to maternal smoking and age at menarche?

Purpose

Studies suggests that intrauterine exposure to maternal smoking both accelerates or delays age at menarche. We hypothesize that these opposing findings relate to different infant and childhood growth patterns across cohorts.

α-葡萄糖苷酶抑制剂治疗2型糖尿病的系统评价

目的评价α-葡萄糖苷酶抑制剂治疗2型糖尿病患者的效果。方法检索Cochrane图书馆、MEDLINE、EMBASE、CurrentContents、LILACS在研试验数据库,主题为α-葡萄糖苷酶抑制剂的综述的参考文献,并联系纳入试验的专家与实施者。最近检索日期为2003年月12月(CurrentContents)和2003年4月(其他数据库)。纳入α-葡萄糖苷酶抑制剂单一疗法与其它干预比较,治疗2型糖尿病疗程至少12周的随机对照试验,并且试验至少包括以下结局之一:病死率、患病率、生活质量、血糖控制、血脂、胰岛素水平、体重、不良事件。两名评价者独立阅读所有摘要,评价质量并提取数据,分歧通过协商解决或由第三位评价者裁决。由一位统计学家在对提取数据输入数据库时进行检查。我们尽量联系所有作者以核实数据。结果共纳入41个试验、8130例受试者,其中30个针对阿卡波糖,7个针对米格列醇,1个针对优格列波糖,还有3个为不同α-葡萄糖苷酶抑制剂间的比较。绝大多数研究疗程为24周,仅有2个研究超过1年。与安慰剂相比,阿卡波糖血糖控制效果更好:糖化血红蛋白–0.8%[95%CI(–0.9,–0.7)],空腹血糖–1.1mmol/L[95%CI(–1.4,–0.9)],负荷血糖–2.3mmol/L[95%CI(–2.7,–1.9)],阿卡波糖对糖化血红蛋白的作用呈非剂量依赖。我们发现其可降低负荷胰岛素,但对血脂和体重未见临床相关的作用。不良反应主要来自胃肠道且与剂量相关。相对于磺脲,阿卡波糖将空腹和负荷胰岛素水平分别降低至–24.8pmol/L[95%CI(–43.3,–6.3)]和–133.2pmol/L[95%CI(–184.5,–81.8)],但阿卡波糖引起的不良反应更多。结论关于α-葡萄糖苷酶抑制剂是否影响2型糖尿病患者的病死率和患病率仍不清楚。相反,其对血糖控制或胰岛素水平作用明显,对血脂和体重的作用差异无统计学意义。α-葡萄糖苷酶抑制剂更长疗程的效果仍不确定。阿卡波糖剂量超过50mg(TID)时不能进一步影响糖化血红蛋白水平,不良反应反而更多,与磺脲相比,α-葡萄糖苷酶抑制剂降低了空腹和负荷胰岛素水平,但在血糖控制和不良反应方面存在不利影响。     

Refrigerated storage of lyophilized and rehydrated, lyophilized human red cells

Human red cells (RBCs) were collected in CPDA-1 and then freeze-dried in lyoprotective solution. The lyophilized RBCs were then stored at -20 degrees C for 7 days. At the end of the storage period, the lyophilized RBCs were rehydrated and washed in dextrose saline. The washed, reconstituted, lyophilized RBCs were resuspended in final wash solutions of ADSOL, CPDA-1, or a special additive solution containing glucose, citrate, phosphate, adenine, and mannitol, and then they were stored at 4 degrees C for an additional 7 days. The main purpose of this study was to determine whether human RBCs can be lyophilized in such a manner that normal metabolic, rheologic, and cellular properties are maintained during rehydration and subsequent storage in standard blood bank preservative solutions. Our results show that reconstituted, lyophilized RBCs maintained levels of ATP, 2,3 DPG, lactate, and cellular properties that are equal to or better than those in control nonlyophilized RBCs stored for a comparable period in CPDA-1. Reconstituted, lyophilized RBCs stored at 4 degrees C after rehydration also show better maintenance of ATP, 2,3 DPG, and lactate than do control RBCs stored in the same preservative solutions for comparable periods.     

Project Kealahou: Improving Hawai‘i's System of Care for At-Risk Girls and Young Women through Gender-Responsive,Trauma-Informed Care

Project Kealahou (PK) is a six-year, federally-funded program aimed at improving services and outcomes for Hawai‘i''s female youth who are at risk for running away, truancy, abuse, suicide, arrest and incarceration. PK builds upon two decades of sustained cross-agency efforts among the state''s mental health, juvenile justice, education, and child welfare systems to promote system-of-care (SOC) principles of community-based, individualized, culturally and linguistically competent, family driven, youth-guided, and evidence-based services. In addition, PK emphasizes trauma-informed and gender-responsive care in serving its target population of females ages 11–18 years who have experienced psychological trauma.Results from the first four years of the implementation of PK in the Department of Health''s (DOH) Child and Adolescent Mental Health Division (CAMHD) highlight the serious familial, socioeconomic, functional, and interpersonal challenges faced by the young women who receive services in Hawai‘i''s SOC. Despite the challenges faced by PK youth and their families, preliminary results of the evaluation of PK show significant improvements across multiple clinical and functional domains of service recipients. A financial analysis indicates that these outcomes were obtained with a minimal overall increase in costs when compared to standard care alone. Overall, these results suggest that PK may offer a cost effective way to improve access, care, and outcomes for at-risk youth and their families in Hawai‘i.     

Quality of life and metabolic control in patients with diabetes mellitus type 1 treated by continuous subcutaneous insulin infusion or multiple daily insulin injections

OBJECTIVE: To assess the quality of life and metabolic control in patients with diabetes mellitus type 1 on continuous subcutaneous insulin infusion (CSII) in comparison with patients on multiple daily insulin injections (MDII). RESEARCH DESIGN AND METHODS: The study included 49 patients (13 males, 36 females), aged 41.4+/-11.3 years (mean+/-SD) on CSII for >1 year and 79 patients (43 males, 36 females), aged 43.1+/-14.8 years on MDII for >1 year, from three Dutch diabetic clinics. There were no statistically significant differences in duration of diabetes, social class, level of education, marital status, smoking or recent admissions to hospital. The questionnaires used were a Diabetes Quality of Life scale adapted from the DCCT, the Diabetes Satisfaction Questionnaire (DTSQ), and the WHO Well-Being Questionnaire. HbA1c was measured with an HPLC method (reference range 4.3 to 6.1 %). RESULTS: Using two-sided t-tests no statiscally significant differences were found between the patients on CSII and MDII with respect to quality of life (version A (<30 years) 4.32+/-0.22 vs 4.20+/-0.30; version B (> or =30 years) 4.18+/-0.25 vs 4.29+/-0.28), well-being (48.59+/-9.23 vs 50.99 +/-8.70), satisfaction with treatment (5.10+/-0.69 vs 5.15+/-0.71) and HbA1c (8.14+/-1.51 vs 8.47+/-1.40). Frequency of daily blood glucose monitoring was slightly higher in CSII than in MDII patients (4.52+/-1.19 vs 3.60+/-1.47; p<0.0001). CONCLUSION: The present data indicate that patients on CSII have similar QoL based on questionnaires when compared with patients on MDII. These data suggest that in patients with less optimal control on MDII, converting the treatment strategy to CSII is not associated with decreased quality of life.     

A double-blind multicenter comparison of the efficacy and safety ofsaruplase andurokinase in thetreatment ofacutemyocardialinfarction: Report of the SUTAMI study group

Background: Urokinase or two-chain urokinasetype plasminogen activator has been shown to be effective in the treatment of acute myocardial infarction. Its parent molecule, single-chain urokinase-type plasminogen activator (scu-PA), unlike urokinase, can selectively activate fibrinbound plasminogen. The induced clot lysis is amplified by plasmin-triggered conversion of scu-PA to urokinase and by further plasmin generation. The aim of our study was to compare the efficacy and safety of recombinant unglycosylated scu-PA, or saruplase, and urokinase at doses considered optimal in patients with acute myocardial infarction within 6 hours of onset of pain. Methods and results: In a double-blind trial 543 patients were randomized to saruplase (20 mg bolus + 60 mg/hr) or urokinase (1.5 million unit bolus + 1.5 million units/hr). Primary endpoint: The patency rates at 24–72 hours were 75.4% (95% CI 70.3–80.5%) for saruplase and 74.2% (95% CI 69.0–79.4%;P=0.77) for urokinase. Secondary endpoint: The incidence of bleeding events in both groups was 10.7%. There were three hemorrhagic strokes in the saruplase group (ns). Other efficacy and safety evaluations: Apart from the generation of more fibrinogen degradation products under saruplase, the changes in hemostatic parameters did not differ. Hospital mortality was 4.4% for saruplase and 8.1% for urokinase. This nonsignificant difference was maintained for 1 year. Conclusion: The efficacy and safety of saruplase and urokinase in the regimens used are very similar.     

Qualitätssicherung an der Schnittstelle zwischen Anästhesie und Transfusionsmedizin

Background

The current situation in hospitals is characterized by financial limitations and simultaneously by increasing demands on quality and safety. The operative interface between anesthesia and transfusion medicine affects both factors.

Aim

A detailed analysis was performed to evaluate the process quality at this operative interface at the University Hospital of Göttingen. The aim of the project was to revise und develop the structures and responsibilities at this interface, to dispose of weak points and to realize the optimization potential in the supply of blood products.

Material and methods

A databank-based electronic data processing solution was established with the clear definition of responsibilities for the various workflow procedures and the written documentation of these definitions in standard operating protocols. In order to guarantee the necessary transparency a routine reporting system to the department of surgery was established. In addition, a continuous further development of the blood supply standard based on electronic report data was implemented.

Results

By implementing the above named measures the rate of supplied to transfused blood products could be increased from 43.1?% to 55.7?%. The compliance with the blood supply standard improved continually over the first 18 months from 60.3?% to 92.3?%. The rate of supplied blood product deliveries without subsequent operation could be reduced from 9.0?% to 4.6??%. As a result of this optimization the supply costs in the internal cost allocation were reduced from 9,406 € to 3,544 €.

Conclusion

The measures described are appropriate to cost-effectively improve quality and patient safety. The optimization measures presented in this article can be implemented in other hospitals to increase quality and safety after individual adjustment to the local circumstances.     

Monoclonal antibody blocking the recognition of an insulin peptide–MHC complex modulates type 1 diabetes

The primary autoantigen triggering spontaneous type 1 diabetes mellitus in nonobese diabetic (NOD) mice is insulin. The major T-cell insulin epitope lies within the amino acid 9–23 peptide of the β-chain (B:9–23). This peptide can bind within the peptide binding groove of the NOD MHC class II molecule (MHCII), IA^g7, in multiple positions or “registers.” However, the majority of pathogenic CD4 T cells recognize this complex only when the insulin peptide is bound in register 3 (R3). We hypothesized that antibodies reacting specifically with R3 insulin–IA^g7 complexes would inhibit autoimmune diabetes specifically without interfering with recognition of other IA^g7-presented antigens. To test this hypothesis, we generated a monoclonal antibody (mAb287), which selectively binds to B:9–23 and related variants when presented by IA^g7 in R3, but not other registers. The monoclonal antibody blocks binding of IA^g7-B:10–23 R3 tetramers to cognate T cells and inhibits T-cell responses to soluble B:9–23 peptides and NOD islets. However, mAb287 has no effect on recognition of other peptides bound to IA^g7 or other MHCII molecules. Intervention with mAb287, but not irrelevant isotype matched antibody, at either early or late stages of disease development, significantly delayed diabetes onset by inhibiting infiltration by not only insulin-specific CD4 T cells, but also by CD4 and CD8 T cells of other specificities. We propose that peptide–MHC-specific monoclonal antibodies can modulate autoimmune disease without the pleiotropic effects of nonselective reagents and, thus, could be applicable to the treatment of multiple T-cell mediated autoimmune disorders.In the nonobese diabetic (NOD) mouse, a spontaneous mouse model of type 1 diabetes mellitus (T1DM), autoimmune targeting of (pro)insulin appears essential for development of disease (1–7). For example, 90 percent of CD4⁺ insulin-reactive T-cell clones isolated from the islets of prediabetic NOD mice target the insulin β-chain 9–23 peptide (B:9–23) (8, 9), and this peptide is likely the primary epitope recognized by T cells that either induce (6, 7, 9) or prevent T1DM (8–14). Similarly, autoimmunity to insulin is essential for the loss of tolerance to the β-cell antigen islet-specific glucose 6 phosphatase catalytic subunit-related protein (IGRP) (11, 15), but the converse is not true. The NOD mouse expresses a single MHC class II (MHCII) molecule, IA^g7, whose presence is essential for the development of T1DM (16–18). We previously suggested that a particular version of IA^g7–insulin B:9–23 complex is crucial for the initiation of islet autoimmunity in the NOD mouse (19–22) and that a homologous complex involving the structurally related MHCII molecules human leukocyte antigen DQ8 (HLA-DQ8) and HLA-DQ2 may play a similar role in humans (23–25).As with other MHCII molecules, the selective binding of peptides to the IA^g7 peptide binding groove is governed by interactions between the side chains at particular positions in the peptide (p1, p4, p6, and p9) with those MHCII amino acids forming four corresponding binding pockets within the groove (26, 27). Thus, peptides can potentially bind in more than one position or register within the groove. Previous work from this group had shown that the pathogenic T cells in NOD T1DM recognize the insulin B:9–23 peptide in register 3 (R3), placing the amino acids B:14–22 in the core p1 to p9 position (28) and placing an Arg at the p9 position, highly unfavored for the IA^g7 p9 pocket. Furthermore, T cells responding to this register can be divided into two groups, one (type A) for which the Glu at p8 is essential for recognition and another (type B) for which this Glu is inhibitory. For the type A group, the peptide is more optimally presented by truncation to remove the p9Arg or, for the type B group, further truncation to remove the p8Glu as well (29). Mimicking these truncations, we have achieved even better presentation of the two epitopes in R3 by using peptide mimotopes in which the p9Arg is substituted with an optimal p9Glu for the type A or, for the type B group of T cells, by removing the offending p8Glu side chain as well by substituting a p8Gly (28). We have used this strategy to prepare IA^g7 with covalently linked versions of these two mimotope peptides, which when incorporated into fluorescent tetramers, detect both types of CD4 T cells in islet infiltrates of prediabetic NOD mice (30).Given the critical role for IA^g7 presentation of the B:9–23 peptide in T1DM development in NOD mice and its unusual presentation to pathogenic T cells, we hypothesized that monoclonal antibodies targeting the IA^g7–R3 complexes would modulate the autoimmune response. Consistent with this idea, our previous study demonstrated that immunization of NOD mice with soluble IA^g7 monomers having the insulin B:9–23 mimotope covalently bound in R3 elicited specific antibodies to the immunogen and, more importantly, significantly delayed the development of insulitis and the onset of diabetes in these animals (22). We now report that a mAb with this specificity, isolated from one immunized mouse, both inhibits pathogenic T cells in vitro and significantly delays the development of diabetes in vivo.