Histopathology of bilateral lower extremity inflammatory lymphedema in military basic trainees: A leukocytoclastic vasculitis of the deep vascular plexus

Bilateral lower extremity inflammatory lymphedema (BLEIL) is a recently described condition that presents with exquisite tenderness, erythema and edema of the lower leg, ankle and dorsal foot resembling an acute cellulitis. It was first reported in healthy, young adult military basic trainees with a normal body mass index during the first 72 hours of arrival to basic training. It occurs while standing at attention for many hours, and shows rapid resolution with elevation and rest. We report an additional case of BLEIL and describe the histopathology of this case and 2 of the previously reported cases. All 3 biopsies showed a deep perivascular infiltrate of neutrophils with karyorrhectic debris and prominent red blood cell extravasation. One of the 3 cases was positive for complement by direct immunofluorescence. We postulate this condition represents a deep leukocytoclastic vascultis with secondary reactive lymphedematous changes.     

Anticoagulant and/or antiplatelet treatment in patients with atrial fibrillation after percutaneous coronary intervention. A single-center experience

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia sustained and frequently occurs in patients with coronary heart disease. Thus, a large number of patients requiring percutaneous coronary intervention (PCI) also suffer from AF. An anticoagulant regimen has not been standardized for patients with AF after coronary stent implantation. PATIENTS AND METHODS: The authors investigated data from 159 patients with AF who underwent PCI in their department. Baseline variables and incidence of a combined endpoint (stroke, myocardial infarction, cardiovascular death, severe bleeding) were compared in patients receiving clopidogrel and acetylsalicylic acid (ASA; group 1) versus patients receiving the combination of clopidogrel and ASA with low-molecular-weight heparin (LMWH; group 2) versus patients receiving the combination of clopidogrel and ASA with oral anticoagulation (OAC; group 3) at discharge. RESULTS: Patients discharged with triple therapy including OAC seemed to be at higher risk: patients in group 3 had decreased left ventricular ejection fraction and increased inflammatory state as measured by plasma fibrinogen and C-reactive protein. Moreover, previous OAC treatment and strokes were found more often in this subgroup of patients. In a median follow-up of 1.4 years, two severe bleeding events (both in group 1), four myocardial infarctions (all in group 1), 13 strokes (nine in group 1, four in group 2), and nine cardiovascular deaths (three in group 1, five in group 2, one in group 3) occurred. CONCLUSION: In this analysis, no treatment regimen seemed to be clearly superior. It underlines the importance of prospective, randomized trials to investigate the optimal antithrombotic/antiplatelet treatment for patients with AF after PCI.     

Proteinase 3–dependent caspase-3 cleavage modulates neutrophil death and inflammation

Caspase-3–mediated spontaneous death in neutrophils is a prototype of programmed cell death and is critical for modulating physiopathological inflammatory responses; however, the underlying regulatory pathways remain ill defined. Here we determined that in aging neutrophils, the cleavage and activation of caspase-3 is independent of the canonical caspase-8– or caspase-9–mediated pathway. Instead, caspase-3 activation was mediated by serine protease proteinase 3 (PR3), which is present in the cytosol of aging neutrophils. Specifically, PR3 cleaved procaspase-3 at a site upstream of the canonical caspase-9 cleavage site. In mature neutrophils, PR3 was sequestered in granules and released during aging via lysosomal membrane permeabilization (LMP), leading to procaspase-3 cleavage and apoptosis. Pharmacological inhibition or knockdown of PR3 delayed neutrophil death in vitro and consistently delayed neutrophil death and augmented neutrophil accumulation at sites of inflammation in a murine model of peritonitis. Adoptive transfer of both WT and PR3-deficient neutrophils revealed that the delayed death of neutrophils lacking PR3 is due to an altered intrinsic apoptosis/survival pathway, rather than the inflammatory microenvironment. The presence of the suicide protease inhibitor SERPINB1 counterbalanced the protease activity of PR3 in aging neutrophils, and deletion of Serpinb1 accelerated neutrophil death. Taken together, our results reveal that PR3-mediated caspase-3 activation controls neutrophil spontaneous death.     

Clinical significance of anti-endothelial cell antibody in allogeneic hematopoietic stem cell transplantation recipients with graft-versus-host disease

Anti-endothelial cell antibody (AECA) is well known to reflect endothelial injury. Graft-versus-host disease (GVHD), a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), is also closely associated with endothelial injury. We hypothesized that AECA may be associated with GVHD. To investigate the clinical significance of AECA in allo-HSCT recipients with GVHD, we detected AECA by cyto-enzyme-linked immunosorbent assay (cyto-ELISA) in allo-HSCT recipients with acute and/or chronic GVHD (aGVHD and cGVHD). Incidences of anti-HMEC-1 AECA (anti-HMEC) and anti-EA.hy926 AECA (anti-EAHY) were significantly higher in patients with grade II–IV than grade 0–I aGVHD (P = 0.049, P = 0.011, respectively). There was no difference in the incidence of AECA between patients with and without cGVHD. Patients with anti-EAHY positive in the early stage post-transplant demonstrated a higher incidence of cGVHD (P = 0.044). In patients with grade 0–I aGVHD, AECA-positive patients had higher overall survival and disease-free survival (P < 0.05), and tended to have lower incidences of relapse and transplant-related mortality. Our data suggest that AECA plays an important role in the pathogenesis of GVHD.     

Associations of established breast cancer risk factors with urinary estrogens in postmenopausal women

Cancer Causes & Control - Circulating estrogens are an established risk factor for postmenopausal breast cancer (BCa). We describe the distribution of urinary estrogens, their metabolites, and...     

驻地不同海拔高度西藏边防军人SCL-90评定结果分析

目的了解不同海拔高度西藏边防军人心理健康状况,为官兵心理健康教育及心理疏导提供科学依据。方法整群随机抽取不同海拔高度1550名高原边防军人,采用心理《症状自评量表》（SCL-90）进行心理健康测评。结果西藏边防军人在躯体化、抑郁、焦虑、敌对、恐怖、精神病性、睡眠饮食等7个因子均高于中国军人常模（P〈0.01或P〈0.05）,但人际敏感与中国军人常模相比降低明显（P〈0.05）;随海拔高度的升高,驻守海拔3500~4300米边防军人在躯体化、敌对、睡眠饮食、人际敏感、抑郁、焦虑、恐怖7个因子均高于驻守海拔3000~3500米边防军人（P〈0.01或P〈0.05）。结论高原对官兵心理健康有影响,且海拔越高其影响作用越明显。     

Central opioid receptors differentially regulate the nalmefene-induced suppression of ethanol- and saccharin-reinforced behaviors in alcohol-preferring (P) rats.

The exact opioid-sensitive receptors participating in EtOH-seeking behaviors remains unclear. Previous studies have reported higher densities of micro-opioid receptor binding in the nucleus accumbens (NACC) of P relative to NP rats; however, no differences were seen in delta-receptor binding. In contrast to the NACC, substantially lower levels of micro-receptor binding have been observed in the ventral tegmental area (VTA) of both P and NP rats, albeit no line differences have been observed. In the present study, opioid receptors in the NACC, VTA, and hippocampus were evaluated for their capacity to regulate both EtOH- and saccharin-motivated behaviors in the genetically selected alcohol-preferring (P) rat. To accomplish this, nalmefene, an opiate antagonist with preferential binding affinity for the micro-opioid receptor was unilaterally or bilaterally infused during concurrent availability of 1 h daily EtOH (10% v/v) and saccharin (0.025 or 0.050% w/v) solutions. Rats performed under a two-lever fixed ratio (FR) schedule in which four responses on one lever produced the EtOH solution, and four on a second lever produced the saccharin solution. The results demonstrated that when responding maintained by both EtOH and saccharin are matched at basal levels, unilateral (1-60 microg) or bilateral (0.5-10 microg) microinjections of nalmefene into the NACC produced selective dose-dependent reductions on responding maintained by EtOH. Unilateral (40, 60 microg) and bilateral (10 microg) VTA infusions were also observed to selectively reduced EtOH responding; however, greater nalmefene doses were required and the magnitude of suppression on EtOH responding was markedly less compared with the NACC. The greater sensitivity of nalmefene to suppress EtOH responding in the NACC is likely due to the greater number of opioid receptors in the NACC relative to the VTA. Only bilateral infusion of the 40 microg dose in the NACC and VTA suppressed responding maintained by both EtOH and saccharin. In contrast, intrahippocampal infusions dose dependently suppressed EtOH- and saccharin-maintained responding over a range of doses (1-20 microg). The present study provides evidence that nalmefene suppresses EtOH-motivated behaviors via blockade of opioid receptors within the NACC and VTA, and under various dose conditions both reinforcer and neuroanatomical specificity can be observed.