Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

去甲硫氨酸全肠外营养对大鼠血清氨基酸谱的影响

目的观察去甲硫氨酸全肠外营养对大鼠血清氨基酸谱等的影响.方法 Wistar大鼠24只,随机分为含甲硫氨酸(+MetTPN,n=12)和去甲硫氨酸全肠外营养2组(-MetTPN,n=12),分别给予相应的TPN支持.治疗7d后,每组随机抽取6只大鼠处死,检测血清FAA(HPLC法)、肝肾功能和全血常规,同时作心、肺、肝、肾组织病理学检查.两组其余大鼠继续原TPN治疗,观察生存期.结果 -MetTPN组大鼠血清游离Met、Cys明显降低,Asp、Glu、Ser等显著增高;大鼠体重下降;血清总蛋白和白蛋白水平下降;血常规和肾功能未见明显异常;组织学检查见肝细胞轻度肿胀,细胞核仁增粗,心肺肾未见明显异常;平均生存18d.对照组上述检查未见异常,除一只大鼠因导管并发症于TPN第16d死亡,其余大鼠全部存活.结论 -MetTPN一周可致大鼠血清游离Met、Cys明显降低和Asp、Glu、Ser等显著增高,及轻度肝功能改变;随着-MetTPN时间延长,出现严重的代谢紊乱和器官功能障碍导致死亡.     

Involving people with dementia in developing an interactive web tool for shared decision-making: experiences with a participatory design approach

Purpose: The aim of this study was at gaining insight into the participatory design approach of involving people with dementia in the development of the DecideGuide, an interactive web tool facilitating shared decision-making in their care networks.

Method: An explanatory case study design was used when developing the DecideGuide. A secondary analysis focused on the data gathered from the participating people with dementia during the development stages: semi-structured interviews (n?=?23), four focus group interviews (n?=?18), usability tests (n?=?3), and a field study (n?=?4). Content analysis was applied to the data.

Results: Four themes showed to be important regarding the participation experiences of involving people with dementia in research: valuable feedback on content and design of the DecideGuide, motivation to participate, perspectives of people with dementia and others about distress related to involvement, and time investment.

Conclusions: People with dementia can give essential feedback and, therefore, their contribution is useful and valuable. Meaningful participation of people with dementia takes time that should be taken into account. It is important for people with dementia to be able to reciprocate the efforts others make and to feel of significance to others.

• Implications for Rehabilitation

• People with dementia can contribute meaningfully to the content and design and their perspective is essential for developing useful and user-friendly tools.

• Participating in research activities may contribute to social inclusion, empowerment, and quality of life of people with dementia.

     

Intestinal over-expression of iron transporters induces iron overload in birds in captivity

Hereditary hemochromatosis (HH) is a frequent genetic disease of older subjects of northern European descent. It is characterized by increased iron absorption and severe iron overloading in parenchymal organs. A similar disturbance of iron metabolism occurs in specific animal species in captivity. To address the key features leading to high absorption and thus to iron overload in these animals, we have studied the two iron transport proteins DMT1 and Ireg1 in the best-known susceptible species, the mynah bird. Here, we show that these birds have a high expression of DMT1 in the duodenum and also a strikingly high expression of Ireg1 along the whole small intestine. We believe that the iron accumulation in susceptible species only occurs in captivity because of a genotypic adaptation to their natural environment, where contrary to captivity, dietary iron is hardly available. The Caucasian population carrying mutations leading to iron overload today may have also benefited from the genetic advantage of up-regulating iron transport millennia ago, when dietary iron was scarce.     

Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).