Family caregiving in pulmonary arterial hypertension

Background

Pulmonary arterial hypertension (PAH) is a devastating disease that places a significant burden on patients and their families. However, family caregiving, to the best of our knowledge, has never been described in this population. This study sought to describe depressive symptoms, types of performed care tasks, social support, and the impact of caregiving among family caregivers of patients with PAH.

Methods and Results

Data were obtained from 35 dyads of patients with PAH (mean age, 51 years; 63% were female; 54% had World Health Organization functional class III symptoms) and their family caregivers (mean age, 52 years; 60% were female; 68% were spouses). Five caregivers (14%) were identified as manifesting moderate to severe depressive symptoms. The majority of caregivers reported that their daily activities were centered around caregiving responsibilities. More than 85% of caregivers were involved in managing care for the patient, and more than half helped the patient with self-management activities. The level of caregivers’ perceived social support was low, especially for emotional and informational support. Lower levels of social support were significantly associated with more severe depressive symptoms in caregivers (r = −.50, P = .002).

Conclusion

Caregivers of patients with PAH play a significant role in patients’ medical care and self-management, yet they lack sufficient emotional support or information to meet the demands of caregiving. These findings underscore the importance of supporting family caregivers of patients with PAH.     

西藏某VCT门诊自愿咨询检测者HIV感染状况分析

目的分析艾滋病自愿咨询检测（VCT）门诊,自愿咨询检测者的艾滋病病毒（HIV）感染状况,为西藏预防HIV传播提供科学依据。方法收集整理2003-2012年西藏某VCT门诊自愿咨询者的人口学信息及HIV抗体检测结果,用描述性方法进行统计分析。结果1929名自愿咨询检测者中,检出HIV抗体阳性188例,阳性率9．75％;女性阳性率（12．94％）高于男性（8．40％）;15～44岁年龄组阳性率达9．92％,其阳性人数占所有阳性者中的94．15％（177／188）。小学及以下文化程度HIV阳性率较高,为17．92％,无业者高于其他职业;静脉注射吸毒阳性率高达62．50％。性传播占总数的89．89％。结论青壮年、小学及以下文化程度者及无业者是感染HIV的高危人群,性接触是主要的传播方式,应针对高危人群的特点,加强艾滋病的宣传教育以及行为干预工作,阻断HIV传播。     

Identification of a distinct low-affinity receptor for human interleukin-4 on pre-B cells

Biotinylated interleukin-4 (IL-4) was used to examine IL-4 receptor (IL- 4R) expression on a range of human B-cell lines by flow cytometry. Using high concentrations of biotinylated IL-4, we have identified a novel low-affinity IL-4 receptor expressed at high levels on pre-B lines. Expression of this low-affinity receptor did not correlate with detected mRNA levels for the previously cloned receptor or with reactivity of two anti-human IL-4R monoclonal antibodies (MoAb). Radiolabeled IL-4 cross-linking studies using pre-B lines showed a doublet of 65 to 75 Kd in contrast to the 110- to 130-Kd molecule detected on cells expressing the cloned IL-4R. A soluble IL-4 binding protein (IL-4bp) was purified from the supernatants of three pre-B lines expressing the low-affinity receptor on their surface. IL-4bp could block both IL-4-mediated CD23 induction on tonsil B cells and IL- 4-induced inhibition of proliferation of the pre-B line JM1. Partial N- terminal amino acid sequence was obtained from purified IL-4bp that confirmed this protein to be novel. A 12 amino acid peptide based on the IL-4bp sequence was used to produce a polyclonal antiserum that was reactive with purified IL-4bp, and also bound to the surface of pre-B cells but not to murine CTLL cells transfected with the human IL-4R. Blocking MoAb against the previously characterized high-affinity receptor inhibited IL-4-mediated proliferation of hIL-4R+ CTLL cells but had no effect on IL-4-induced inhibition of JM1 cell proliferation, and only partially inhibited IL-4-mediated CD23 and sIgM induction and proliferation of tonsil B cells. The data presented here provide evidence for a novel cell-surface expressed low-affinity IL-4R that also exists as a biologically active soluble IL-4 binding protein.     

Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase [see comments]

We analyzed the outcome of 450 HLA-identical sibling bone marrow transplants for chronic myelogenous leukemia (CML) in chronic phase performed between 1985 and 1990 and reported to the International Bone Marrow Transplant Registry (IBMTR). All patients received either hydroxyurea (n = 292) or busulfan (n = 158) to treat their CML before transplant. The median interval between diagnosis and transplant was 10 months (range, 1 to 191). Patients treated with hydroxyurea had a higher probability (95% confidence interval) of leukemia-free survival (LFS) at 3 years than those treated with busulfan (61% [51% to 70%] v 45% [36% to 55%], P < .0003). Probability of LFS was also higher in patients transplanted within 1 year of diagnosis (61% [53 to 68%] v 47% [38% to 57%], P < .001). After adjustment for patient and transplant covariables in a multivariate analysis, prior chemotherapy and duration of disease pretransplant were independently associated with LFS. These data support the use of hydroxyurea rather than busulfan and transplant within 1 year of diagnosis for patients with CML and an HLA-identical sibling.     

Comparative analysis of type 2b von Willebrand disease mutations: implications for the mechanism of von Willebrand factor binding to platelets

von Willebrand factor (vWF) is a multimeric glycoprotein that forms an adhesive link following vascular injury between the vessel wall and its primary ligand on the platelet surface, glycoprotein Ib (GpIb). Type 2b von Willebrand disease (vWD) is a qualitative form of vWD resulting from enhanced binding of vWF to platelets. Molecular characterization of the vWF gene in patients with type 2b vWD has resulted in identification of a panel of mutations associated with this disorder, all clustered within the GpIb binding domain in exon 28 of the vWF gene. We have expressed six of the most common type 2b vWD mutations in recombinant vWF and show that each mutation produces a similar increase in vWF binding to platelets in the absence or presence of ristocetin. Furthermore, expression of more than one type 2b vWD mutation in the same molecule (cis) or in different molecules within the same multimer (trans) failed to produce an increase in vWF platelet binding compared with any of the individually expressed mutations. Taken together, these data support the hypothesis that the vWF GpIb binding domain can adopt either a discrete "on" or "off" conformation, with most type 2b vWD mutations resulting in vWF locked in the on conformation. This model may have relevance to other adhesive proteins containing type A domains.     

B cell growth factor-induced proliferation of hairy cell lymphocytes and inhibition by type I interferon in vitro

Malignant B cells from hairy cell leukemia (HCL) patients are unable to proliferate when stimulated with standard B cell mitogens. Using chromatographically purified B cell growth factor (BCGF), HCL can be stimulated to proliferate as assessed by incorporation of tritiated thymidine [3HTdR] into DNA. Proliferation was found to be time dependent, with no detectable 3H-TdR incorporation in up to three days of culture, and significant stimulation evident at days 6 and 10. The presence of 10% BCGF in culture was an absolute requirement for HCL proliferation; however, this BCGF-induced DNA synthesis could be further augmented by the addition of anti-immunoglobulin heavy chain antibodies. BCGF-induced proliferation was abrogated in six of six patients by addition of 1,000 U/mL of recombinant alpha 2-interferon (IFN) at day 0, although 1,000 U/mL of recombinant gamma-IFN had no inhibitory effect in five of six patients studied. Specific cellular receptors for type I IFN were demonstrated in HCL by inhibition of binding of 125I-alpha 2-IFN by a 40-fold excess of unlabeled alpha 2 or beta IFN with no inhibition by unlabeled gamma-IFN. These data demonstrate that malignant HCL lymphoblasts express specific type I IFN receptors and that type I, but not type II IFN, can inhibit growth factor-induced DNA synthesis by hairy cells in vitro. They further suggest a direct antiproliferative mechanism of action for IFN in HCL and predict equivalent clinical activity by either alpha or beta, but not gamma IFN in this malignancy.     

损伤性癫痫模型大鼠海马和额叶突触蛋白的动态表达

目的 通过观察FeCl2皮层注射致损伤性癫痫(PTE)模型大鼠海马、额叶突触蛋白P38的表达变化.探讨突触可塑性在PTE发病机制中的作用. 方法 健康成年雄性SD大鼠采用随机数字表法分为正常对照组(n=5)、假手术组(n=12)、模型组(n=20).采取立体定向皮层注射FeCl2(0.1 moL/L,10μL)建立PTE模型,假手术组注入等量生理盐水,正常对照组不做处理.观察各组大鼠EEG的变化并应用免疫组织化学方法 检测大鼠造模后不同时间点(1 h、7 d、14 d、30 d)海马、额叶P38的表达. 结果大多数模型组大鼠在注射FeCl2后不久记录到癫痫样放电;与假手术组比较,模型组不同时间点右侧额叶P38表达减少.差异有统计学意义(P<0.05);与正常对照组和假手术组比较,致痫1h后,CA3区多形层、辐射层、腔隙层和齿状回(DG)分子层P38表达均无明显变化,7 d后P38表达增加,维持到30d,差异均有统计学意义(P<0.05). 结论 与突触蛋白P38表达相关的突触可塑性变化在PTE的发病机制中可能起重要作用.     

The erroneous perception of a clinical sign: Cholestasis preceding sepsis mimicking hepatitis in an adolescent patient

Jaundice should be considered as a first clinical sign preceding severe invasive bacterial infection or sepsis in patients of all ages including childhood and adolescence. Early laboratory investigations and MR imaging studies for osteomyelitis or myositis are paramount to avoid progression to life‐threatening sepsis and significant morbidity and mortality.