tbuckley/cabot-search huggingface dataset:
Obesity in Adulthood and Its Consequences for Life Expectancy: A Life-Table Analysis
Authors: Anna Peeters, Jan J. Barendregt, Frans Willekens, Johan P. Mackenbach, Abdullah Al Mamun, Luc Bonneux
Journal: Annals of Internal Medicine (2003)

Background: Overweight and obesity in adulthood are linked to an increased risk for death and disease. Their potential effect on life expectancy and premature death has not yet been described. Objective: To analyze reductions in life expectancy and increases in premature death associated with overweight and obesity at 40 years of age. Design: Prospective cohort study. Setting: The Framingham Heart Study with follow-up from 1948 to 1990. Participants: 3457 Framingham Heart Study participants who were 30 to 49 years of age at baseline. Measurements: Mortality rates specific for age and body mass index group (normal weight, overweight, or obese at baseline) were derived within sex and smoking status strata. Life expectancy and the probability of death before 70 years of age were analyzed by using life tables. Results: Large decreases in life expectancy were associated with overweight and obesity. Forty-year-old female nonsmokers lost 3.3 years and 40-year-old male nonsmokers lost 3.1 years of life expectancy because of overweight. Forty-year-old female nonsmokers lost 7.1 years and 40-year-old male nonsmokers lost 5.8 years because of obesity. Obese female smokers lost 7.2 years and obese male smokers lost 6.7 years of life expectancy compared with normal-weight smokers. Obese female smokers lost 13.3 years and obese male smokers lost 13.7 years compared with normal-weight nonsmokers. Body mass index at ages 30 to 49 years predicted mortality after ages 50 to 69 years, even after adjustment for body mass index at age 50 to 69 years. Conclusions: Obesity and overweight in adulthood are associated with large decreases in life expectancy and increases in early mortality. These decreases are similar to those seen with smoking. Obesity in adulthood is a powerful predictor of death at older ages. Because of the increasing prevalence of obesity, more efficient prevention and treatment should become high priorities in public health. *For members of the Netherlands Epidemiology and Demography Compression of Morbidity Research Group, see Appendix.
Effects of Th1 and Th2 cytokines on cytokine production and ICAM-1 expression on synovial fibroblasts.
Authors: J F Schlaak, A Schwarting, P Knolle, K H Meyer zum Buschenfelde, W Mayet
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVES--To investigate the influence of the Th1 and Th2 lymphokines interleukins (IL)-4 and IL-13, interferon gamma (IFN gamma), and several monokines on the adhesion of mononuclear cells to synovial fibroblasts and intercellular adhesion molecule-1 (ICAM-1) expression and cytokine production of synovial fibroblasts in patients with osteoarthritis. METHODS--Synovial fibroblasts were isolated from patients with osteoarthritis and stimulated with IL-1 beta, IL-4, IL-6, IL-10, IL-12, IL-13, tumour necrosis factor alpha (TNF alpha), and IFN gamma. Subsequently, we determined the production of IL-1 alpha, IL-1 beta, IL-6, IL-10, IL-12, IFN alpha and TNF alpha, and the expression of ICAM-1 lymphocyte function associated antigen 3 (LFA-3), BB7, and major histocompatibility complex class II molecules on these cells. Furthermore, the adhesion of freshly isolated mononuclear cells from the peripheral blood was tested using a colourimetric cell-cell adhesion assay. RESULTS--Only production of IL-6 and the expression of ICAM-1 were observed. IL-1 beta and TNF alpha were the most potent stimulatory mediators of both cytokine production and ICAM-1 expression. IL-4 and IL-13 had differential effects as they upregulated cytokine production but downregulated IFN gamma induced ICAM-1 expression. In functional adhesion assays, TNF alpha, IL-1 alpha and, to a lesser extent, IFN gamma led to increased adhesion of mononuclear cells, whereas IL-4 and IL-13 had no effect. CONCLUSIONS--Our data indicate that Th1 and Th2 lymphokines can modulate the function (cytokine production and expression of adhesion molecules) of synovial fibroblasts.
Suppression of Prostate Tumor Cell Growth by Stromal Cell Prostaglandin D Synthase–Derived Products
Authors: Jeri Kim, Peiying Yang, Milind Suraokar, Anita L. Sabichi, Norma D. Llansa, Gabriela Mendoza, Vemparalla Subbarayan, Christopher J. Logothetis, Robert A. Newman, Scott M. Lippman, David G. Menter
Journal: Cancer Research (2005)

Abstract Stromal-epithelial interactions and the bioactive molecules produced by these interactions maintain tissue homeostasis and influence carcinogenesis. Bioactive prostaglandins produced by prostaglandin synthases and secreted by the prostate into seminal plasma are thought to support reproduction, but their endogenous effects on cancer formation remain unresolved. No studies to date have examined prostaglandin enzyme production or prostaglandin metabolism in normal prostate stromal cells. Our results show that lipocalin-type prostaglandin D synthase (L-PGDS) and prostaglandin D2 (PGD2) metabolites produced by normal prostate stromal cells inhibited tumor cell growth through a peroxisome proliferator–activated receptor γ (PPARγ)–dependent mechanism. Enzymatic products of stromal cell L-PGDS included high levels of PGD2 and 15-deoxy-Δ12,14-PGD2 but low levels of 15-deoxy-Δ12,14-prostaglandin J2. These PGD2 metabolites activated the PPARγ ligand-binding domain and the peroxisome proliferator response element reporter systems. Thus, growth suppression of PPARγ-expressing tumor cells by PGD2 metabolites in the prostate microenvironment is likely to be an endogenous mechanism involved in tumor suppression that potentially contributes to the indolence and long latency period of this disease.
Twenty-Year Follow-up of the Royal Marsden Randomized, Double-Blinded Tamoxifen Breast Cancer Prevention Trial
Authors: T. J. Powles, S. Ashley, A. Tidy, I. E. Smith, M. Dowsett
Journal: JNCI Journal of the National Cancer Institute (2007)

Several clinical trials have reported an early reduction in breast cancer incidence in healthy women using tamoxifen to reduce their risk of breast cancer but have not reported longer follow-up data for the evaluation of breast cancer prevention. We report the blinded 20-year follow-up (median follow-up = 13 years) of the Royal Marsden trial to identify any long-term prevention of breast cancer associated with tamoxifen treatment.We randomly assigned 2494 healthy women to oral tamoxifen (20 mg/day) or placebo for 8 years. The primary outcome was occurrence of invasive breast cancer. A secondary planned analysis of estrogen receptor (ER)-positive invasive breast cancer was also done. Survival was assessed by use of a Cox proportional hazards model in both univariate and multivariable analyses. The durability of the treatment effect was assessed by use of a Cox regression analysis. All statistical tests were two-sided.Among the 2471 eligible participants (1238 participants in the tamoxifen arm and 1233 participants in the placebo arm), 186 developed invasive breast cancer (82 on tamoxifen and 104 on placebo; hazard ratio [HR] = 0.78, 95% confidence interval [CI] = 0.58 to 1.04; P = .1). Of these 186 cancers, 139 were ER positive (53 on tamoxifen and 86 on placebo; HR = 0.61, 95% CI = 0.43 to 0.86; P = .005). The risk of ER-positive breast cancer was not statistically significantly lower in the tamoxifen arm than in the placebo arm during the 8-year treatment period (30 cancers in the tamoxifen arm and 39 in the placebo arm; HR = 0.77, 95% CI = 0.48 to 1.23; P = .3) but was statistically significantly lower in the posttreatment period (23 in the tamoxifen arm and 47 in the placebo arm; HR = 0.48, 95% CI = 0.29 to 0.79; P = .004). Fifty-four participants in each arm have died from any cause (HR = 0.99, 95% CI = 0.68 to 1.44; P = .95). The adverse event profiles for both arms were similar to those previously reported and occurred predominantly during the treatment period.A statistically significant reduction in the incidence of ER-positive breast cancer was observed in the tamoxifen arm that occurred predominantly during the post treatment follow-up, indicating long-term prevention of estrogen-dependent breast cancer by tamoxifen.
European Antibiotic Awareness Day, 2008 – the first Europe-wide public information campaign on prudent antibiotic use: methods and survey of activities in participating countries
Authors: S Earnshaw, D L Monnet, B Duncan, J O’Toole, K Ekdahl, H Goossens, None the European Antibiotic Awareness D, None the European Antibiotic Awareness D
Journal: Eurosurveillance (2009)

Antibiotic resistance is a major European and global public health problem and is, for a large part, driven by misuse of antibiotics. Hence, reducing unnecessary antibiotic use, particularly for the treatment of certain respiratory tract infections where they are not needed, is a public health priority. The success of national awareness campaigns to educate the public and primary care prescribers about appropriate antibiotic use in Belgium and France stimulated a European initiative coordinated by the European Centre for Disease Prevention and Control (ECDC), and named "European Antibiotic Awareness Day" (EAAD), to take place each year on 18 November. Specific campaign materials, including key messages, logos, slogans and a media toolkit, were developed and made available for use in European countries. The focus of the first EAAD campaign was about not taking antibiotics for viral infections such as colds and flu. A post-campaign survey was conducted in January 2009. Thirty-two European countries participated in the first EAAD, producing information materials and implementing activities to mark EAAD. Media coverage peaked on 18 and 19 November. At EU level, EAAD was launched at a scientific meeting in the European Parliament, Strasbourg. The event received EU political engagement through support from the EU Commissioner for Health, the Slovenian and French EU Presidencies, and Members of the European Parliament. Critical factors that led to the success of the first EAAD were good cooperation and process for building the campaign, strong political and stakeholder support and development of campaign materials based on scientific evidence. Countries indicated wide support for another EAAD in 2009. For this purpose, ECDC is developing several TV spots as well as a second set of EAAD campaign materials targeting primary care prescribers.
P97 Multi-drug resistant tuberculosis: The first UK guideline for treatment monitoring
Authors: JL Keal, TG Capstick, WM Ricketts, N Whitehead, OM Kon
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Multi-drug resistant tuberculosis (MDR-TB) is a growing concern<sup>1</sup>. Cost of treatment is ten times that of fully sensitive TB. Treatment regimens are complex and prolonged with risk of serious adverse drug reactions (ADRs). Previously no single guidance in the UK has been available to inform clinicians on what baseline testing should be performed and how to monitor for ADRs<sup>2</sup>. We would like to introduce the first UK guideline for adverse-effect monitoring in MDR-TB. <h3>Methods</h3> This document has been written using the best available evidence and, where this is limited, expert consensus. Our multi-disciplinary guideline group held regular teleconferences and corresponded by email. When evidence was sparse, expert consensus was sought from the British Thoracic Society TB Special Advisory Group (SAG) and UK MDR-TB Advisory Service. When other specialty input was needed this was sought from experts in that field. Once the guideline was developed it was submitted to the TB SAG for peer review. <h3>Results</h3> <b>'</b>MDR-TB: A guideline for treatment monitoring' includes direction on baseline and generic monitoring throughout treatment and individual drug monographs for all drugs currently used to treat MDR-TB in the UK. At the time of writing it is due to be published online, later this month, and will be available on the BTS website (www.brit-thoracic.org.uk). <h3>Conclusions</h3> We hope that by introducing a guideline to aid ADR monitoring in MDR-TB treatment we can improve morbidity and mortality and reduce treatment costs. By the time of the BTS Winter Meeting we will have nearly six months experience of this guideline being used in practice and will present any feedback received. In due course we plan to audit its use and publish our experiences. <h3>References</h3> WHO. <i>Global Tuberculosis Report</i>. (2012). Keal, J. L., Khachi, H., Hanzaree, E. &amp; White, V. L. C. Treatment of multidrug resistant tuberculosis: where are the guidelines for monitoring? <i>Thorax</i><b>66,</b> A91–A91 (2011).
Response of the nose to exercise in healthy subjects and in patients with rhinitis and asthma.
Authors: J Serra-Batlles, J M Montserrat, J Mullol, E Ballester, A Xaubet, C Picado
Journal: Thorax (1994)

BACKGROUND--Although the nose and the bronchi are both involved in the process of regulating respiratory heat exchange, thermal changes may precipitate airway obstruction during exercise but rarely cause nasal obstruction in patients with rhinitis. The cause of the different response of the nose and bronchial tree has hardly been investigated. This study was performed to assess the response of the nose during exercise in the presence of rhinitis, asthma, and in normal controls. METHODS--Ten healthy subjects (group 1), 15 patients with asthma and rhinitis (group 2), 10 with rhinitis only (group 3), and 11 with asthma only (group 4) were included in the study. Exercise was performed on a bicycle ergometer for six minutes, reaching a heart rate of 80% of predicted. Bronchial and nasal responses were measured by forced expiratory volume in one second (FEV1) and posterior rhinomanometry, respectively. A drop in the FEV1 of 20% or more was considered a positive exercise induced asthma challenge test. RESULTS--Heart rate and ventilation increased by a similar proportion in the four groups. The FEV1 significantly decreased in asthmatic patients (groups 2 and 4) but it did not change in healthy subjects (group 1) or in those with rhinitis (group 3). Thirteen asthmatic patients developed exercise induced asthma. Nasal patency increased with exercise by a similar proportion in all groups, and no differences were detected between those with rhinitis (groups 2 and 3) and those without (groups 1 and 4). Nasal patency had returned to basal values at 25 minutes after completion of exercise in the four groups. The nose of patients with exercise induced asthma, however, remained significantly more patent than in patients without exercise induced asthma between 10 and 30 minutes after exercise. CONCLUSIONS--These results suggest that the nose responds differently from the bronchi during exercise induced airway obstruction: whereas the bronchial tree responds by becoming narrowed, the nose becomes more patent. These findings suggest that the mechanisms regulating the response of the nose to exercise are different from those involved in the response of the bronchial tree.
Distinct Patterns of Cytokine and Angiogenic Factor Modulation and Markers of Benefit for Vandetanib and/or Chemotherapy in Patients With Non–Small-Cell Lung Cancer
Authors: Emer O. Hanrahan, Heather Y. Lin, Edward S. Kim, Shaoyu Yan, Danny Z. Du, Kathryn S. McKee, Hai T. Tran, J. Jack Lee, Anderson J. Ryan, Peter Langmuir, Bruce E. Johnson, John V. Heymach
Journal: Journal of Clinical Oncology (2009)

Purpose There is an unmet need for biomarkers for identifying patients likely to benefit from anticancer treatments, selecting dose, and understanding mechanisms of resistance. Plasma vascular endothelial growth factor (VEGF) and soluble VEGF receptor 2 (sVEGFR-2) are known to be modulated by VEGF pathway inhibitors. It is unknown whether chemotherapy or VEGFR inhibitor/chemotherapy combinations induce changes in these or other cytokines and angiogenic factors (CAFs) and whether such changes could be markers of benefit. Methods Thirty-five plasma CAFs were analyzed using multiplexed bead arrays and enzyme-linked immunosorbent assays from 123 patients with non–small-cell lung cancer in a randomized phase II study who received vandetanib, a VEGFR and epidermal growth factor receptor inhibitor, monotherapy carboplatin and paclitaxel (CP), or the combination (VCP). Changes in CAFs at days 8, 22, and 43 from baseline were correlated with progression risk. Results VEGF increased and sVEGFR-2 decreased by day 43 in the vandetanib arm, whereas a distinct pattern was observed in the CP and VCP arms, with significant decreases in interleukin (IL) -12, IL-1 receptor antagonist, and matrix metalloproteinase 9 (MMP-9) and increased macrophage chemoattractant protein 1. In each treatment arm, changes in different markers were associated with progression risk. For example, increases in IL-8 with VCP, MMP-9 with CP, and VEGF with vandetanib monotherapy were associated with increased progression risk, and increase in intercellular adhesion molecule 1 with vandetanib was associated with decreased risk. Conclusion Vandetanib and chemotherapy treatment led to distinct patterns of CAF changes; the combination resembled chemotherapy alone. Changes in specific CAFs correlated with clinical outcome, but markers differed for each treatment arm. CAF profiling may provide insights into the biologic effects of treatment and identify drug-specific markers of activity and clinical benefit.
Council of Europe condemns "unjustified scare" over swine flu
Authors: A. O'Dowd
Journal: BMJ (2010)

The Council of Europe has heavily criticised the World Health Organization, national governments, and EU agencies for their handling of the swine flu pandemic.

The parliamentary assembly of the council—the international organisation that protects human rights and the rule of law in Europe—published a draft of a report that reviewed how the H1N1 pandemic was handled.

National governments, WHO, and EU agencies had all been guilty of actions that led to a “waste of large sums of public money, and unjustified scares and fears about the health risks faced by the European public,” says the report.

The conclusion came in the parliamentary assembly’s social, health and family affairs committee report published on 4 June.

The report was prepared by Paul Flynn, socialist member of the assembly and Labour MP for Newport West and approved by the committee ahead of a plenary debate at the end of this month. It says there was overwhelming evidence that the seriousness of the pandemic was vastly over-rated by WHO, which led to a …
Screening for Oral Cancer: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2013)

Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for oral cancer.The USPSTF reviewed the evidence on whether screening for oral cancer reduces morbidity or mortality and on the accuracy of the oral screening examination for identifying oral cancer or potentially malignant disorders that have a high likelihood of progression to oral cancer.This recommendation applies to asymptomatic adults aged 18 years or older who are seen by primary care providers. This recommendation focuses on screening of the oral cavity performed by primary care providers and not dental providers or otolaryngologists.The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for oral cancer in asymptomatic adults.
Immunotherapy and the belly of the beast
Authors: Taha Merghoub, Jedd D. Wolchok
Journal: The Journal of Experimental Medicine (2014)

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Insight from Taha Merghoub (left) and Jedd Wolchok (right)



Immunotherapy has emerged as an effective means to restore immune recognition of cancer. Numerous forms of immunotherapy are currently being explored clinically. The most common are vaccines (dendritic cell, viral, and
Chemical analysis of whole saliva in Sjogren's syndrome.
Authors: A M Nahir, R Szargel, J Scharf, H Ben-Aryeh, D Laufer, Y Scharf
Journal: Annals of the Rheumatic Diseases (1987)

In some studies, but not in all, abnormally high concentrations of salivary Na+, K+, and IgA have been found in patients with Sjögren's syndrome (SS). The lack of agreement between various reports might be due to the different ways in which saliva was collected. Some analysed stimulated parotid or whole saliva, whereas others used unstimulated saliva. In this study, therefore, the rate of flow and Na+, K+, and IgA levels in unstimulated and stimulated whole saliva in normals and in rheumatoids with and without SS have been determined. The results confirmed significantly raised levels of Na+, K+, and IgA in unstimulated whole saliva in SS. In response to stimulation there was marked decrease in Na+, K+, and IgA levels, whereas normally, as shown by the other two groups, there is an increase in Na+, no change in K+, and a mild decrease in IgA. As a result, the differences between SS and normals became much less significant (K+, IgA) or were even completely obliterated (Na+). The abnormal response of SS to stimulation may be partially explained by the initially low rate of flow and by the extremely high IgA levels. Thus chemical analysis of unstimulated whole saliva is much more sensitive than analysis of stimulated whole saliva in the detection of salivary gland involvement in SS.
Contribution of general practitioner hospitals in Scotland.
Authors: J A Grant
Journal: BMJ (1984)

The results of a survey of 64 Scottish general practitioner hospitals showed that in 1980 these hospitals contained 3.3% of available staffed beds in Scotland; 13.6% of the resident population had access for initial hospital care, and 14.5% of Scottish general practitioners were on their staffs. During the year of the survey they discharged 1.8% of all non-surgical patients, treated almost 100 000 patients for accidents and emergencies and 140 000 outpatients, and 4.4% of all deliveries in Scotland were carried out in the hospitals surveyed. Most communities which are served by general practitioner hospitals in Scotland are rural and on average are more than 30 miles from their nearest district general hospital. The contribution that these small hospitals make to the overall hospital workload has not previously been estimated. It has been shown nationally to be small but not inconsiderable . In terms of the contribution to the health care of the communities they serve it cannot and should not be underestimated.
THE PRESSURE-FLOW RELATIONSHIPS OF THE INTRATHORACIC AIRWAY IN MAN*
Authors: Robert E. Hyatt, Roger E. Wilcon
Journal: Journal of Clinical Investigation (1963)

Measurement of the pressure-flow relationships of the human respiratory tract is basic to the study of ventilatory mechanics. The relationship of respiratory air flow to the total pressure drop along the respiratory tree (alveolus to mouth) has been extensively studied and been shown to depend on lung inflation (1-3) and the type and degree of airway disease (4). Recently the total pressure drop has been partitioned into that occurring along the lower or intrathoracic airways (alveolus to trachea) and that along the upper or extrathoracic airways (trachea to mouth) (5, 6). The resistance of the upper airway with mouth breathing was found 1) to comprise a significant portion of the total airway resistance in normal subjects, 2) to vary from subject to subject as well as in a given subject, 3) to depend on the type of breathing maneuver employed, and 4) to vary inversely