Blood-brain barrier disruption in CCL2 transgenic mice during pertussis toxin-induced brain inflammation

BACKGROUND: The chemokine CCL2 has an important role in the recruitment of inflammatory cells into the central nervous system (CNS). A transgenic mouse model that overexpresses CCL2 in the CNS shows an accumulation of leukocytes within the perivascular space surrounding vessels, and which infiltrate into the brain parenchyma following the administration of pertussis toxin (PTx). METHODS: This study used contrast-enhanced magnetic resonance imaging (MRI) to quantify the extent of blood–brain barrier (BBB) disruption in this model pre- and post-PTx administration compared to wild-type mice. Contrast-enhanced MR images were obtained before and 1, 3, and 5 days after PTx injection in each animal. After the final imaging session fluorescent dextran tracers were administered intravenously to each mouse and brains were examined histologically for cellular infiltrates, BBB leakage and tight junction protein. RESULTS: BBB breakdown, defined as a disruption of both the endothelium and glia limitans, was found only in CCL2 transgenic mice following PTx administration and seen on MR images as focal areas of contrast enhancement and histologically as dextrans leaking from blood vessels. No evidence of disruption in endothelial tight junctions was observed. CONCLUSION: Genetic and environmental stimuli were needed to disrupt the integrity of the BBB in this model of neuroinflammation

Risk factors for COPD spirometrically defined from the lower limit of normal in the BOLD project.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Chronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and disability worldwide by 2020. The prevalence of COPD defined by the lower limit of normal was estimated using high-quality spirometry in surveys of 14 populations aged ≥ 40 yrs. The strength and consistency of associations were assessed using random effects meta-analysis. Pack-years of smoking were associated with risk of COPD at each site. After adjusting for this effect, we still observed significant associations of COPD risk with age (OR 1.52 for a 10 yr age difference, 95% CI 1.35-1.71), body mass index in obese compared with normal weight (OR 0.50, 95% CI 0.37-0.67), level of education completed (OR 0.76, 95% CI 0.67-0.87), hospitalisation with a respiratory problem before age 10 yrs (OR 2.35, 95% CI 1.42-3.91), passive cigarette smoke exposure (OR 1.24, 95% CI 1.05-1.47), tuberculosis (OR 1.78, 95%CI 1.17-2.72) and a family history of COPD (OR 1.50, 95% CI 1.19-1.90). Although smoking is the most important risk factor for COPD, other risk factors are also important. More research is required to elucidate relevant risk factors in low- and middle-income countries where the greatest impact of COPD will occur.ALTANA Aventis AstraZeneca Boehringer-Ingelheim Chiesi GlaxoSmithKline Merck Novartis Pfizer Schering-Plough Sepracor University of Kentucky Boehringer Ingelheim China (Guangzhou, China) Turkish Thoracic Society Pfizer (Adana, Turkey) Merck Sharpe Dohme Salzburger Gebietskrankenkasse Salzburg Local Government (Salzburg, Austria) Research for International Tobacco Control International Development Research Centre South African Medical Research Council South African Thoracic Society GlaxoSmithKline University of Cape Town Lung Institute (Cape Town, South Africa) Landspitali-University Hospital GlaxoSmithKline Iceland AstraZeneca Iceland (Reykjavik, Iceland) GlaxoSmithKline Pharmaceuticals Polpharma Ivax Pharma Poland AstraZeneca Pharma Poland ZF Altana Pharma Pliva Krakow Linde Gaz Polska Novartis Poland Lek Polska Farmaceutyczne Polfa Starostwo Proszowice Skanska Zasada Agencja Mienia Wojskowego w Krakowie Telekomunikacja Polska Biernacki Amplus Bucki Skrzydlewski Sotwin Agroplon (Krakow, Poland) Pfizer Germany (Hanover, Germany) Norwegian Ministry of Health's Foundation for Clinical Research Haukeland University Hospital's Medical Research Foundation for Thoracic Medicine (Bergen, Norway) GlaxoSmithKline (Vancouver, Canada) Marty Driesler Cancer Project (Lexington, KY, USA) Philippine College of Chest Physicians Boehringer Ingelheim (Phil) Philippine College of Physicians United Laboratories (Phil) (Manila, Philippines) Air Liquide Healthcare P/L AstraZeneca P/L Boehringer Ingelheim P/L GlaxoSmithKline Australia P/L Pfizer Australia P/L (Sydney, Australia) UK Department of Health's Policy (London, UK) Swedish Heart-Lung Foundation Swedish Heart and Lung Association GlaxoSmithKline (Uppsala, Sweden) Adamed Lek Polska Biogra

Gender Specific Differences in the Pros and Cons of Smoking among Current Smokers in Eastern Kentucky: Implications for Future Smoking Cessation Interventions

This study investigated gender differences in the perceived “pros” and “cons” of smoking using the constructs of decisional balance (DB) and stage of change from the Transtheoretical Model. The population distribution for stage of change among a population-based, cross-sectional survey of 155 current smokers over 40 years was: precontemplation (22.6%), contemplation (41.9%), preparation (35.5%). Results of stepwise regression models indicated significant gender differences in DB were in the preparation stage of change; scores on the DB measure increased 3.94 points (95% CI: 1.94, 5.93) for male smokers. Interventions targeting the “pros” and “cons” of smoking may need to be gender specific

Selective strategy for solid sorbent replacement in CCS

An innovative method for sorbent replacement in the looping of a generic solid sorbent for post-combustion carbon capture and sequestration (CCS) is introduced. First, the standard replacement method is revisited with some original results presented. A new strategy is then modeled, aimed at selectively replacing the material as it degrades. This method exploits the density difference, after adsorption, between relatively fresh, CO2-laden sorbent and relatively degraded material, with small residual adsorption capacity. The model is then applied to values of degradation rate within the experimental range available in scientific literature for silica-supported amines (SSA). The selective removal strategy ideally allows a saving of 37% of the sorbent with respect to the standard, undifferentiated replacement considered in first place, while keeping the same adsorptive capacity of the system

Improving Together: A National Framework for Quality and GP Clusters in Scotland

Improving together will complement the development of the Scottish national GP contract that sets out the role of GPs and their important contribution as clinical leaders and expert medical generalists working in a community setting. This framework will be reviewed by the Scottish Government and the Scottish General Practitioners Committee of the BMA on a periodic basis, attentive to feedback from those involved in delivering its intent. As such, it is a framework that will develop to its full potential over time, as elements of the transformation of primary care in Scotland create the capacity to do so

Bone mineral density and the subsequent risk of cancer in the NHANES I follow-up cohort

BACKGROUD: Bone mineral density (BMD) is a marker of long-term estrogen exposure. BMD measurement has been used in this context to investigate the association of estrogen with breast cancer risk in three cohorts. In order to assess further BMD as a predictor of estrogen related cancer risk, the association of BMD with colorectal and corpus uteri cancer was investigated in the NHANES I Epidemiologic Followup Study (NHEFS) cohort along with breast cancer and prostate cancer. METHODS: Participants were members of the NHEFS cohort who had BMD measurement in 1974–1975. Age, race, and BMI adjusted rate ratios and 95% confidence intervals were calculated for incidence of cancers of the corpus uterus, breast, colorectum, prostate, and of osteoporosis and hip fracture related to baseline BMD. RESULTS: Data were available for 6046 individuals. One hundred cases of breast cancer, 94 prostate cancers, 115 colorectal cancers, 29 uterine cancers, 110 cases of hip fracture and 103 cases of osteoporosis were reported between 1974 and 1993. Hip fracture and osteoporosis were both significantly inversely associated with BMD. Uterine cancer was positively associated (p = 0.005, test for linear trend) and colorectal cancer negatively associated (p = 0.03) with BMD. No association was found between elevated BMD and incidence of breast cancer (p = 0.74) or prostate cancer (p = 0.37) in the overall cohort, although a weak association was seen between BMD and subsequent breast cancer incidence when BMD was measured in post-menopausal women (p = 0.04). CONCLUSION: The findings related to cancers of the uterus and colorectum as well as the weak association of BMD with breast cancer strengthen the use of BMD as a marker of estrogen exposure and cancer risk

From open radical hysterectomy to robot-assisted laparoscopic radical hysterectomy for early stage cervical cancer: aspects of a single institution learning curve

We analysed the introduction of the robot-assisted laparoscopic radical hysterectomy in patients with early-stage cervical cancer with respect to patient benefits and surgeon-related aspects of a surgical learning curve. A retrospective review of the first 14 robot-assisted laparoscopic radical hysterectomies and the last 14 open radical hysterectomies in a similar clinical setting with the same surgical team was conducted. Patients were candidates for a laparoscopic sentinel node procedure, pelvic lymph node dissection and open radical hysterectomy (RH) before August 2006 and were candidates for a laparoscopic sentinel node procedure, pelvic lymph node dissection and robot-assisted laparoscopic radical hysterectomy (RALRH) after August 2006. Overall, blood loss in the open cases was significantly more compared with the robot cases. Median hospital stay after RALRH was 5 days less than after RH. The median theatre time in the learning period for the robot procedure was reduced from 9 h to less that 4 h and compared well to the 3 h and 45 min for an open procedure. Three complications occurred in the open group and one in the robot group. RALRH is feasible and of benefit to the patient with early stage cervical cancer by a reduction of blood loss and reduced hospital stay. Introduction of this new technique requires a learning curve of less than 15 cases that will reduce the operating time to a level comparable to open surgery