Impaired coronary flow reserve in patients with non-ischemic heart failure

INTRODUCTION AND OBJECTIVES: Coronary flow reserve (CFR) is impaired not only in ischemic heart disease, but also in cardiac diseases that may or may not course with heart failure. The aim of the present study was to determine if the severity of heart failure can influence CFR impairment. METHODS: Forty patients with non-ischemic heart disease and heart failure were studied 41 times. Four groups were established: 1. 10 patients in functional class III-IV; 2. 10 patients in functional class II not taking beta-blockers; 3. 11 patients in class II treated with carvedilol, and 4. 10 patients in class I. These patients had a history of heart failure and systolic dysfunction. Myocardial blood flow (MBF) was measured with positron emission tomography (PET) and N-13 ammonia at rest (r) and during adenosine triphosphate (ATP) infusion. RESULTS: MBF and CFR were significantly higher in group 4 (1.95 0.58 and 2.40 0.95 ml/min/g) than in group 1 (1.02 0.52 and 1.46 0.48 ml/min/g). CFR tended to be higher in groups 2 (1.73 0.72), and 3 (1.89 0.75) vs group 1. No significant correlation was found between CFR and the following variables: age, systolic blood pressure, ventricular mass index, ventricular volume indexes, and ejection fraction. CONCLUSIONS: Coronary microvascular function is impaired in non-ischemic heart failure, and the impairment is related to functional class, regardless of the underlying responsible heart disease.     

Aerosol release,distribution, and prevention during aerosol therapy: a simulated model for infection control

Aerosol therapy is used to deliver medical therapeutics directly to the airways to treat respiratory conditions. A potential consequence of this form of treatment is the release of fugitive aerosols, both patient derived and medical, into the environment and the subsequent exposure of caregivers and bystanders to potential viral infections. This study examined the release of these fugitive aerosols during a standard aerosol therapy to a simulated adult patient. An aerosol holding chamber and mouthpiece were connected to a representative head model and breathing simulator. A combination of laser and Schlieren imaging was used to non-invasively visualize the release and dispersion of fugitive aerosol particles. Time-varying aerosol particle number concentrations and size distributions were measured with optical particle sizers at clinically relevant positions to the simulated patient. The influence of breathing pattern, normal and distressed, supplemental air flow, at 0.2 and 6 LPM, and the addition of a bacterial filter to the exhalation port of the mouthpiece were assessed. Images showed large quantities of fugitive aerosols emitted from the unfiltered mouthpiece. The images and particle counter data show that the addition of a bacterial filter limited the release of these fugitive aerosols, with the peak fugitive aerosol concentrations decreasing by 47.3–83.3%, depending on distance from the simulated patient. The addition of a bacterial filter to the mouthpiece significantly reduces the levels of fugitive aerosols emitted during a simulated aerosol therapy, p≤ .05, and would greatly aid in reducing healthcare worker and bystander exposure to potentially harmful fugitive aerosols.     

Interleukin-1-Mediated phospholipid breakdown and arachidonic acid release in human synovial cells

Objective. Interleukin-1 (IL-1), an important mediator contributing to joint destruction in rheumatoid arthritis, is known to stimulate the release of arachidonic acid (AA) and prostaglandin E₂ (PGE₂) from adherent synoviocytes. To study the intracellular pathways involved in these functions, we stimulated cultures of human synovial cells with recombinant IL-1β. Methods. AA liberation was measured after labeling synovial cells with ³H-AA, and PGE₂ levels were determined by high performance liquid chromatography or radioimmunoassay. Identification of ³H-AA-labeled phospholipids was performed by thin layer chromatography. Cell-associated phospholipase A₂ (PLA₂) enzymatic activity was determined by an assay with cell-free systems and exogenous substrates. Results. Stimulation of synovial cells with recombinant IL-1β induced a decrease in phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE), and a marked increase in cell-associated PLA₂ activity as compared with controls. In the presence of either quinacrine, an inhibitor of PLA₂ pathway activation, or neomycin, which binds to PI mono- and biphosphate thus blocking their degradation by phospholipases, AA and PGE₂ secretion were reduced in a dose-dependent manner. Kinetic studies revealed that quinacrine had little blocking activity on the IL-1-mediated AA release after 1 hour of stimulation but completely abolished it after 5 or 8 hours. In contrast, neomycin exerted a partial but significant inhibitory effect from the first hour of stimulation onward. Addition of quinacrine was also demonstrated to abolish the IL-1-induced hydrolysis of PC and PE but not PI, indicating that PC and PE are the preferred substrates for PLA₂ enzymatic activity in human synovial cells. Conclusion. Our findings strongly suggest that AA and PGE₂ production by IL-1-triggered synoviocytes are largely dependent upon PLA₂-mediated hydrolysis of PC and PE and to a lesser extent upon the earlier degradation of PI.     

Increasing Engagement for Breast Cancer Screening and Treatment: The “ICANTREAT” Community of Expertise Initiative

Background: Incidence of breast cancer and associated mortality are on the rise globally. Breast cancer incidence in India is on the rise and also accounts for a staggering 50% mortality rate among women. Health illiteracy, socio-economic and cultural barriers in addition to lack of an organized nationwide screening and prevention programme contribute to poor patient outcomes. Thus, it is imperative to strengthen the existing screening and treatment facilities to address the increasing cancer burden. In this regard, we conducted a workshop to investigate the scope of a multi- stakeholder engagement in breast cancer screening and treatment. Methods: A stakeholder workshop grounded in an established co-design methodology  was convened in a semi-urban coastal district in South India with active participation of physicians, surgeons, occupational therapists, community leaders, programme officers, public health professionals and breast cancer survivors. Shiffman and Smith’s framework was adapted to highlight barriers to screening and role of stakeholders in the co-design of solutions. Results: Deliberate and active discussions marked the workshop proceedings resulting in the identification of   individual and systems level barriers, facilitators and implementation strategies. Social stigma and non-existent standard protocols for screening and referral were recognised as critical barriers, while community engagement and a dedicated patient advocate were the proposed facilitators.Conclusion: This workshop was an important step in bringing together key stakeholders and marked the beginning of the ICANTREAT initiative and a Community of Expertise. The outcomes highlight the importance of stakeholder involvement in the cancer- care pathway for breast cancer screening, diagnosis and treatment.     

Multidisciplinary management of liver metastases in patients with colorectal cancer: a consensus of SEOM,AEC, SEOR,SERVEI, and SEMNIM

Clinical and Translational Oncology - Colorectal cancer (CRC) has the second-highest tumor incidence and is a leading cause of death by cancer. Nearly 20% of patients with CRC will have metastases...     

采用同伴推动抽样法进行男男性接触人群 HIV/STD流行病学调查的探索

目的探索同伴推动抽样法(Respondent driven sampling,RDS)在我国男男性接触(MSM)人群调查的可行性。方法使用RDS对北京市MSM进行抽样调查及血清学检测,了解他们艾滋病病毒(HIV)、性病感染状况及行为特点;采用RDSAT软件进行统计分析,NETDRAW和EXCEL作图。结果共征募MSM 325人,其中35岁以下占90.5%,未婚占83.0%(95%CI:76.4~88.9),外地户籍为61.9%(95%CI:54.0~70.1);HIV感染率为0.4%(95%CI:0.1~0.5),梅毒抗体阳性率为13.7%(95%CI:9.1~19.0),梅毒RPR阳性率6.0%(95%CI:3.8~8.7);56.2%(95%CI:50.0~65.0)为男性性取向,88.9%首次性行为年龄≤24岁,56.3%(95%CI:49.5~64.0)半年内有≥2个性伴,近6个月无保护插入性肛交为51.8%(95%CI:44.0~59.4),无保护被插入性肛交为44.8%(95%CI:37.2~52.3)。结论RDS简便易行,无需过多调查员投入前期准备工作,实为开展隐匿人群调查的行之有效的方法之一。北京市MSM人群HIV感染率可能处于低水平,但存在HIV流行隐患。     

A new PTGDR promoter polymorphism in a population of children with asthma

Recently, functional genetic variants of the PTGDR gene have been associated with asthma. The objective of this work was to study polymorphisms of the promoter region of PTGDR and their haplotype and diplotype combinations in a Spanish population of children with asthma. In this study, 200 Caucasian individuals were included. Asthma was specialist–physician diagnosed according to the ATS criteria. The polymorphisms were analyzed by direct sequencing. In the study, the new polymorphism (-613C > T) in the promoter region of PTGDR was analyzed. The CT genotype was more common in controls (17%) than in patients with asthma (1%) (p-value = 0.0003; OR, 0.057; 95% CI, 0.007–0.441). The CCCT CCCC diplotype (promoter positions -613, -549, -441, and -197) was more frequent in the group of patients with asthma [Fisher's p-value = 0.012; OR, 10.24; 95% CI (1.25–83.68)]; this diplotype is unambiguous. To our knowledge, this is the first study of -613C > T PTGDR polymorphism in patients. This analysis provides more complete information on influence of diplotype combinations of PTGDR polymorphisms in asthma.