Fibrin D-dimer measurement in suspected pulmonary embolism

Due to increased awareness among physicians, the prevalence of pulmonary embolism (PE) in patients clinically suspected of the disease has steadily decreased during the past 15 years. This has led to the development of simple diagnostic tools in an attempt to reduce the number of invasive or costly exams needed to manage these patients. D-dimer (DD) measurement has proven to be a simple and very useful test to exclude PE and several strategies combining DD with clinical probability and other exams have been validated in large outcome studies. The problem faced by many physicians is the choice of the specific DD test and its more appropriate position in the diagnostic work-up of patients suspected of PE. This article focuses on these questions and also provides some limitations of DD use, such as its poor specificity in hospitalized and elderly patients.     

Hemodynamic Effect of Propafenone and the Experience in Patients with Congestive Heart Failure

The effects of propafenone on left ventricular function and hemodynamics are presented in this study. In one group of 13 patients who underwent electrophysiological testing and subsequent chronic oral therapy with propafenone, eight had left ventricular ejection fractions determined by nuclear study before and during therapy with the drug. Initial measurements ranged from 22% to 39% (mean 30%), while those on chronic therapy showed no statistical difference and ranged from 22% to 48% (mean 30%). In a separate dose titration study of 14 patients, left ventricular ejection fraction showed a modest but significant decrease (52%± 9% to 48%± 11%; p < 0.05). This change was more marked in patients with an initial low ejection fraction. Propafenone appears to be safe in these patients but should be administered with caution in patients with particularly low ejection fractions.     

Correlates of resistance to HIV-1 infection in homosexual men with high-risk sexual behaviour

OBJECTIVE: To investigate possible correlates of HIV resistance in participants from the Amsterdam Cohort of Homosexual men who have remained HIV seronegative despite high-risk sexual behaviour. DESIGN/METHODS: We studied in vitro HIV-1 susceptibility and adaptive and innate immunity in 29 high-risk seronegative (HRSN) and 15 HIV-negative pre-seroconversion (pre-SC) homosexual men from the same Amsterdam Cohort Study (ACS) who seroconverted to HIV-1 positive during active follow-up. Host genetics were compared between HRSN and HIV-positive ACS participants. RESULTS: We found lower in vitro susceptibility for a CCR5-using (R5) HIV-1 variant, higher RANTES production levels, but no difference in coreceptor expression in HRSN as compared with pre-SC controls. Reduced R5 in vitro susceptibility of two HRSN tested was restored to normal levels by addition of antibodies against beta-chemokines. A higher proportion of HRSN carried the SDF-1 3'A variant and HLA-A*11, A*31 and Cw*15 alleles. ELIspot analysis with HIV-1 peptide stimulation revealed low frequencies of HIV-1-specific CD8 interferon-gamma producing cytotoxic T cells in both HRSN and pre-SC controls. CONCLUSIONS: Low in vitro R5 susceptibility of cells from the HRSN men was due to beta-chemokine mediated inhibition of virus replication. The presence of HIV-1 specific cytotoxic T cells in both HRSN and pre-SC participants may signify exposure to the virus rather than protection from infection. Host genetic characteristics and other factors affecting innate immunity may contribute to differential resistance to HIV-1 infection among exposed seronegative individuals.     

Timescales of developmental toxicity impacting on research and needs for intervention

Much progress has happened in understanding developmental vulnerability to preventable environmental hazards. Along with the improved insight, the perspective has widened, and developmental toxicity now involves latent effects that can result in delayed adverse effects in adults or at old age and additional effects that can be transgenerationally transferred to future generations. Although epidemiology and toxicology to an increasing degree are exploring the adverse effects from developmental exposures in human beings, the improved documentation has resulted in little progress in protection, and few environmental chemicals are currently regulated to protect against developmental toxicity, whether it be neurotoxicity, endocrine disruption or other adverse outcome. The desire to obtain a high degree of certainty and verification of the evidence used for decision‐making must be weighed against the costs and necessary duration of research, as well as the long‐term costs to human health because of delayed protection of vulnerable early‐life stages of human development and, possibly, future generations. Although two‐generation toxicology tests may be useful for initial test purposes, other rapidly emerging tools need to be seriously considered from computational chemistry and metabolomics to CLARITY‐BPA‐type designs, big data and population record linkage approaches that will allow efficient generation of new insight; epigenetic mechanisms may necessitate a set of additional regulatory tests to reveal such effects. As reflected by the Prenatal Programming and Toxicity (PPTOX) VI conference, the current scientific understanding and the timescales involved require an intensified approach to protect against preventable adverse health effects that can harm the next generation and generations to come. While further research is needed, the main emphasis should be on research translation and timely public health intervention to avoid serious, irreversible and perhaps transgenerational harm.     

CLARITY‐BPA academic laboratory studies identify consistent low‐dose Bisphenol A effects on multiple organ systems

Bisphenol A (BPA) is a high‐production chemical used in a variety of applications worldwide. While BPA has been documented as an endocrine‐disrupting chemical (EDC) having adverse health‐related outcomes in multiple studies, risk assessment for BPA has lagged due to reliance on guideline toxicology studies over academic ones with end‐points considered more sensitive and appropriate. To address current controversies on BPA safety, the United States National Institute of Environmental Health Sciences (NIEHS), the National Toxicology Program (NTP) and the Food and Drug Administration (FDA) established the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY‐BPA) using the NCTR Sprague‐Dawley rats. The goal of CLARITY‐BPA is to perform a traditional regulatory toxicology study (Core study) in conjunction with multiple behavioural, molecular and cellular studies by academic laboratories focused on previously identified BPA‐sensitive organ systems (Academic studies). Combined analysis of the data from both study types will be undertaken by the NTP with the aim of resolving uncertainties on BPA toxicity. To date, the Core study has been completed and a draft report released. Most of the academic studies have also been finalized and published in peer‐reviewed journals. In light of this important milestone, the PPTOX‐VI meeting held in the Faroe Islands, 27‐30 May 2018 devoted a plenary session to CLARITY‐BPA with presentations by multiple investigators with the purpose of highlighting key outcome. This MiniReview synthesizes the results of three academic studies presented at this plenary session, evaluates recently published findings by other CLARITY‐BPA academic studies to provide an early combined overview of this emerging data and places this in the context of the Core study findings. This co‐ordinated effort revealed a plethora of significant BPA effects across multiple organ systems and BPA doses with non‐monotonic responses across the dose range utilized. Remarkably consistent across most studies, including the Core study, are low‐dose effects (2.5, 25 and 250 μg BPA/kg body‐weight). Collectively, the findings highlighted herein corroborate a significant body of evidence that documents adverse effects of BPA at doses relevant to human exposures and emphasizes the need for updated risk assessment analysis.     

食品药品检验检测信息化建设发展现状与经营介绍——以山东省食品药品检验研究院为例

本文总结了我院2016~2018信息化全面建设工作,包括机房、网络和应用系统建设,重点介绍实验室信息管理系统（LIMS）建设情况、经验和教训,以期为全国食品药品检验检测单位的信息化建设工作提供参考。