tbuckley/cabot-search huggingface dataset:
Serum γ-Glutamyltransferase and Risk of Metabolic Syndrome and Type 2 Diabetes in Middle-Aged Japanese Men
Authors: Noriyuki Nakanishi, Kenji Suzuki, Kozo Tatara
Journal: Diabetes Care (2004)

OBJECTIVE—To investigate the association between serum γ-glutamyltransferase (GGT) and risk of metabolic syndrome and type 2 diabetes in Japanese male office workers. RESEARCH DESIGN AND METHODS—This study included 2,957 metabolic syndrome-free men and 3,260 nondiabetic men aged 35–59 years who did not have medication for hepatitis, alanine aminotransferase (ALT) levels higher than three times the upper limit of the reference range, or a history of cardiovascular disease at study entry. Subjects were reexamined at periodic annual health examinations over a 7-year period. We used a modified National Cholesterol Education Program definition of metabolic syndrome with BMI instead of waist circumference and the revised criteria of the American Diabetes Association for type 2 diabetes. RESULTS—With adjustment for age, family history of diabetes, BMI, alcohol intake, cigarette smoking, regular physical activity (fasting plasma glucose for the risk of type 2 diabetes), and white blood cell (WBC) count, the risk of metabolic syndrome and type 2 diabetes increased in correlation with the levels of serum GGT, ALT, aspartate aminotransferase (AST), and alkaline phosphatase. Additional adjustment for all of the other liver enzymes attenuated these associations, but serum GGT remained a significant risk factor for the risk of both metabolic syndrome and type 2 diabetes (P for trend &amp;lt;0.001 for both). Top one-fifth versus bottom one-fifth relative risks of metabolic syndrome and type 2 diabetes were 2.23 (95% CI 1.51–3.30) and 2.44 (1.34–4.46), respectively. CONCLUSIONS—These results indicate that serum GGT may be an important predictor for developing metabolic syndrome and type 2 diabetes in middle-aged Japanese men.
Bleomycin-induced pulmonary fibrosis in fibrinogen-null mice
Authors: Noboru Hattori, Jay L. Degen, Thomas H. Sisson, Hong Liu, Bethany B. Moore, Raj G. Pandrangi, Richard H. Simon, Angela F. Drew
Journal: Journal of Clinical Investigation (2000)

Mice deleted for the plasminogen activator inhibitor-1 (PAI-1) gene are relatively protected from developing pulmonary fibrosis induced by bleomycin. We hypothesized that PAI-1 deficiency reduces fibrosis by promoting plasminogen activation and accelerating the clearance of fibrin matrices that accumulate within the damaged lung. In support of this hypothesis, we found that the lungs of PAI-1–/– mice accumulated less fibrin after injury than wild-type mice, due in part to enhanced fibrinolytic activity. To further substantiate the importance of fibrin removal as the mechanism by which PAI-1 deficiency limited bleomycin-induced fibrosis, bleomycin was administered to mice deficient in the gene for the Aα-chain of fibrinogen (fib). Contrary to our expectation, fib–/– mice developed pulmonary fibrosis to a degree similar to fib+/– littermate controls, which have a plasma fibrinogen level that is 70% of that of wild-type mice. Although elimination of fibrin from the lung was not in itself protective, the beneficial effect of PAI-1 deficiency was still associated with proteolytic activity of the plasminogen activation system. In particular, inhibition of plasmin activation and/or activity by tranexamic acid reversed both the accelerated fibrin clearance and the protective effect of PAI-1 deficiency. We conclude that protection from fibrosis by PAI-1 deficiency is dependent upon increased proteolytic activity of the plasminogen activation system; however, complete removal of fibrin is not sufficient to protect the lung.
Effect of Electric Aversion on Cigarette Smoking
Authors: M. A. H. Russell
Journal: BMJ (1970)

Electric aversion was administered to 14 cigarette smokers. Six of the nine who completed the treatment were still abstinent at one-year follow-up. Three cases relapsed (at one, three, and four months) and five dropped out of treatment. Depression was a troublesome side-effect and was responsible for two of the drop-outs. The overall average of 21.5 cigarettes on the day before treatment dropped to an average of 1.4 cigarettes per day after the third aversion session, and though individual response varied widely most patients stopped smoking within five sessions. It is concluded that electric aversion is a powerful suppressor of cigarette smoking, but more experience is needed to ensure its best use as a measure to achieve permanent abstinence. Its use is limited to a small group of well-motivated smokers.
NHS is still failing older minority ethnic patients who are mentally ill
Authors: A. O'Dowd
Journal: BMJ (2009)

The UK NHS is still failing older ethnic minority patients who are mentally ill, concludes a report from the Royal College of Psychiatrists.

Although some examples of good practice exist, Psychiatric Services for Black and Minority Ethnic Older People claims that progress in developing and improving services for them “has been slow,” with little improvement made since the publication of the college’s previous report on the matter in 2001.

Research shows that dementia and depression are as common, or more common, in older people from minority ethnic groups in the United Kingdom than among older white UK residents, says …
A Study of the Pathogenesis of Malignant Lymphoma Induced in the Swiss Mouse by 7,12-Dimethylbenz[a]anthracene Injected at Birth
Authors: Henry Rappaport, Carlo Baroni
Journal: Cancer Research (1962)

A single lymphoma-inducing dose (100 µg.) of 7,12-dimethylbenz[ a ]anthracene (DMBA) injected subcutaneously into newborn Swiss mice results in rapid cellular depletion of the thymic cortex and of the myelopoietic tissues. Although regenerative activity in the thymus starts as early as the 3d day following injection, evidence of cellular regeneration in the bone marrow does not become apparent until the 2d week. It appears that, at the time of maximum regenerative activity of the thymic cortex, the DMBA-injected newborn mouse does not possess a normally functioning bone marrow, which is regarded by some as essential to normal regeneration of injured thymic cortex. As regeneration proceeds, a relatively wide subcapsular zone of undifferentiated cells persists considerably longer in the thymus of the DMBA-injected mouse than in that of the untreated animal. After the 5th week a sustained increase in mitotic activity may be the only microscopic abnormality in the thymic cortex. Regeneration of the bone marrow proceeds until, by the 4th week, no appreciable histologic differences between DMBA-treated and untreated animals can be recognized. Malignant lymphoma, usually of the stem-cell type, can be detected as early as the 8th week, at which time it is limited to the thymus. The unicentric origin of this neoplasm is indicated by the observation of instances in which only one lobe or one relatively small focus of one lobe of the thymus is involved. This predilection for the thymus can be correlated with the observation that the lymphocytes of the thymic cortex appear to be more susceptible to the cytotoxic action of DMBA than those in extrathymic lymphatic tissues. Our findings indicate that malignant lymphoma induced in the Swiss mouse by the subcutaneous administration of DMBA at birth is not disseminated from its inception but is a malignant tumor arising in one organ if not from one focus.
AMG 706, an Oral, Multikinase Inhibitor that Selectively Targets Vascular Endothelial Growth Factor, Platelet-Derived Growth Factor, and Kit Receptors, Potently Inhibits Angiogenesis and Induces Regression in Tumor Xenografts
Authors: Anthony Polverino, Angela Coxon, Charlie Starnes, Zobedia Diaz, Thomas DeMelfi, Ling Wang, James Bready, Juan Estrada, Russell Cattley, Stephen Kaufman, Danlin Chen, Yongmei Gan, Gondi Kumar, James Meyer, Sesha Neervannan, Gonzalo Alva, Jane Talvenheimo, Silvia Montestruque, Andrew Tasker, Vinod Patel, Robert Radinsky, Richard Kendall
Journal: Cancer Research (2006)

The growth of solid tumors is dependent on the continued stimulation of endothelial cell proliferation and migration resulting in angiogenesis. The angiogenic process is controlled by a variety of factors of which the vascular endothelial growth factor (VEGF) pathway and its receptors play a pivotal role. Small-molecule inhibitors of VEGF receptors (VEGFR) have been shown to inhibit angiogenesis and tumor growth in preclinical models and in clinical trials. A novel nicotinamide, AMG 706, was identified as a potent, orally bioavailable inhibitor of the VEGFR1/Flt1, VEGFR2/kinase domain receptor/Flk-1, VEGFR3/Flt4, platelet-derived growth factor receptor, and Kit receptors in preclinical models. AMG 706 inhibited human endothelial cell proliferation induced by VEGF, but not by basic fibroblast growth factor in vitro, as well as vascular permeability induced by VEGF in mice. Oral administration of AMG 706 potently inhibited VEGF-induced angiogenesis in the rat corneal model and induced regression of established A431 xenografts. AMG 706 was well tolerated and had no significant effects on body weight or on the general health of the animals. Histologic analysis of tumor xenografts from AMG 706-treated animals revealed an increase in endothelial apoptosis and a reduction in blood vessel area that preceded an increase in tumor cell apoptosis. In summary, AMG 706 is an orally bioavailable, well-tolerated multikinase inhibitor that is presently under clinical investigation for the treatment of human malignancies.
Prospective Study of Sudden Cardiac Death Among Women in the United States
Authors: Christine M. Albert, Claudia U. Chae, Francine Grodstein, Lynda M. Rose, Kathryn M. Rexrode, Jeremy N. Ruskin, Meir J. Stampfer, JoAnn E. Manson
Journal: Circulation (2003)

There are few data regarding the determinants of sudden cardiac death (SCD) in women, primarily because of their markedly lower rate of SCD compared with men. Nonetheless, existing data, although sparse, suggest possible gender differences in risk factors for SCD.In this prospective cohort of 121 701 women aged 30 to 55 years at baseline, SCD was defined as death within 1 hour of symptom onset. From 1976 to 1998, 244 SCDs were identified. Although the risk of SCD increased markedly with age, the percentage of cardiac deaths that were sudden decreased. Most (69%) women who suffered a SCD had no history of cardiac disease before their death. However, almost all of the women who died suddenly (94%) had reported at least 1 coronary heart disease risk factor. Smoking, hypertension, and diabetes conferred markedly elevated (2.5- to 4.0-fold) risk of SCD, similar to that conferred by a history of nonfatal myocardial infarction (relative risk, 4.1; 95% confidence interval, 2.9 to 6.7). Family history of myocardial infarction before age 60 years and obesity were associated with moderate (1.6-fold) elevations in risk. With regard to mechanism, 88% of SCDs were classified as arrhythmic. In 76% of these, the first rhythm documented was ventricular tachycardia or ventricular fibrillation.These prospective data suggest that, as in men, coronary heart disease risk factors predict risk of SCD in women and that SCD is usually an arrhythmic death. Therefore, prevention of atherosclerosis or ventricular arrhythmias may reduce the incidence of SCD in women.
A Genome-Wide Association Study of Cockroach Sensitization among African American Asthmatics
Authors: P.S. Gao, R.A. Mathias, N.M. Rafaels, A.V. Grant, T. Hand, N. Hansel, G. Diette, N.F. Adkinson, M.C. Liu, M. Faruque, G.M. Dunston, A.F. Scott, I. Ruczinski, T.H. Beaty, K.C. Barnes
Journal: Journal of Allergy and Clinical Immunology (2008)
Nomogram for Predicting the Likelihood of Delayed Graft Function in Adult Cadaveric Renal Transplant Recipients
Authors: William D. Irish, David A. McCollum, Raymond J. Tesi, Art B. Owen, Daniel C. Brennan, Jane E. Bailly, Mark A. Schnitzler
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Delayed graft function (DGF) is the need for dialysis in the first week after transplantation. Studied were risk factors for DGF in adult (age ≥16 yr) cadaveric renal transplant recipients by means of a multivariable modeling procedure. Only donor and recipient factors known before transplantation were chosen so that the probabilities of DGF could be calculated before transplantation and appropriate preventative measures taken. Data on 19,706 recipients of cadaveric allografts were obtained from the United States Renal Data System registry (1995 to 1998). Graft losses within the first 24 h after surgery were excluded from the analysis ( n = 89). Patients whose DGF information was missing or unknown ( n = 2820) and patients missing one or more candidate predictors ( n = 2951) were also excluded. By means of a multivariable logistic regression analysis, factors contributing to DGF in the remaining 13,846 patients were identified. After validating the logistic regression model, a nomogram was developed as a tool for identifying patients at risk for DGF. The incidence of DGF was 23.7%. Sixteen independent donor or recipient risk factors were found to predict DGF. A nomogram quantifying the relative contribution of each risk factor was created. This index can be used to calculate the risk of DGF for an individual by adding the points associated with each risk factor. The nomogram provides a useful tool for developing a pretransplantation index of the likelihood of DGF occurrence. With this index in hand, better informed treatment and allocation decisions can be made. E-mail: wirish@rti.org
The influence of climate type on injury epidemiology in european professional football
Authors: M Waldén, M Hägglund, K Kristenson, J Ekstrand
Journal: British Journal of Sports Medicine (2011)

Background The influence of different weather conditions on injury risk has only been scarcely investigated. Objective The objective was to study the influence of climate type on injury epidemiology in men's professional football in Europe. Design Prospective cohort study. Setting Men's professional football from nine European football associations. Participants 24 clubs followed over a varying number of seasons from 2001/2002 to 2008/2009. Assessment of risk factors The assessed risk factor was the climate type according to the Köppen-Geiger Climate Classification System. This system is divided into five climate types based on the average monthly temperature and precipitation. The dominating climate types in Europe are the Mediterranean, the Marine West Coast (MWC), the Humid Continental, and the Subarctic types. Main outcome measurements The main outcome measure was the difference in time-loss injury incidence between clubs with Mediterranean (MED) and MWC climate types expressed as a rate ratio (RR) with 95% CI. Results Excluding one club belonging to the Humid Continental climate type, there were 16 clubs in MWC group (61 team-seasons) and seven clubs in the MED group (40 team-seasons). The MED group had significantly lower incidence of training (3.5 vs 4.4/1000 h, RR 0.79, 95% CI 0.72 to 0.86) and match (25.5 vs 29.1/1000 h, RR 0.88, 95% CI 0.81 to 0.94) injuries. There were no differences for severe injuries (RR 0.95, 95% CI 0.82 to 1.09), strains (RR 1.05, 95% CI 0.95 to 1.15) or sprains (RR 0.89, 95% CI 0.78 to 1.02). However, the incidence of anterior cruciate ligament (ACL) injury was higher (0.087 vs 0.042/1000 h, RR 2.07, 95% CI 1.10 to 3.90) in the MED group, especially for non-contact ACL injuries (0.083 vs 0.012/1000 h, RR 6.72, 95% CI 2.53 to 17.83). Conclusion Clubs with a Mediterranean climate type had lower injury risk in general, but a substantially higher risk of non-contact ACL injury.
Multicenter phase II study of weekly oral vinorelbine for stage IV non-small-cell lung cancer.
Authors: E E Vokes, R K Rosenberg, M Jahanzeb, J B Craig, R J Gralla, C P Belani, S E Jones, J W Bigley, J A Hohneker
Journal: Journal of Clinical Oncology (1995)

PURPOSE We initiated a large multicenter phase II trial in stage IV non-small-cell lung cancer (NSCLC) to evaluate the activity and safety of an oral gelatin-based formation of vinorelbine. PATIENTS AND METHODS Twenty-three centers participated in this uncontrolled phase II study, which accrued patients between August 1991 and March 1992. Eligible patients had previously untreated measurable or assessable stage IV NSCLC, age more than 18 years, and Karnofsky performance status &gt; or = 70%. The treatment plan initially was to administer 100 mg/m2/wk of oral vinorelbine or 80 mg/m2/wk for patients who had received prior radiation therapy. After the observation of grade IV granulocytopenia in six of the first 25 patients, subsequent doses were reduced by 40 mg (one capsule) in all patients. RESULTS One hundred sixty-two patients were treated: 138 with measurable and 24 with assessable disease. One hundred two patients were men and 60 women. The mean age was 62 years (range, 36 to 83). The overall response rate was 14.5% for patients with measurable disease (95% confidence interval, 9.3% to 21.7%). The median time to treatment failure (TTF) for all patients was 9 weeks. The median survival time was 29 weeks; the 1-year survival rate was 22%. Toxicities included grade 3 or 4 neutropenia in 40%, which was dependent on the vinorelbine dose. Other toxicities included mild to moderate nausea/vomiting, diarrhea, and stomatitis. The mean dose intensity of vinorelbine was 53 mg/m2. CONCLUSION Oral vinorelbine administered once weekly is an active agent in stage IV NSCLC. The median survival time of 29 weeks is similar to that achieved with single-agent intravenous vinorelbine and more aggressive cisplatin-based combinations. Further studies of this compound in the palliative-intent care setting appear to be indicated.
Alterations in NF B Activation in T Lymphocytes of Patients With Renal Cell Carcinoma
Authors: R. G. Uzzo, P. E. Clark, P. Rayman, T. Bloom, L. Rybicki, A. C. Novick, R. M. Bukowski, J. H. Finke
Journal: JNCI Journal of the National Cancer Institute (1999)
Spontaneous Regression of Grade 3 Vulvar Intraepithelial Neoplasia Associated with Human Papillomavirus-16–Specific CD4+ and CD8+ T-Cell Responses
Authors: Isabelle Bourgault Villada, Micheline Moyal Barracco, Marianne Ziol, Aude Chaboissier, Nathalie Barget, Sophie Berville, Bernard Paniel, Eric Jullian, Thierry Clerici, Bernard Maillère, Jean Gérard Guillet
Journal: Cancer Research (2004)

Abstract Cell-mediated immunity directed against human papillomavirus 16 (HPV-16) antigens was studied in six patients affected with grade 3 vulvar intraepithelial neoplasia (VIN3, also known as bowenoid papulosis). Five of the patients presented with a chronic and persistent disease that relapsed after destructive treatments. They showed no detectable anti-HPV blood T-cell responses and no T-cell intraepidermal vulvar infiltrate containing both CD4+ and CD8+ lymphocytes. The last patient had a complete clearance of viral lesions, 8 months after disease onset and 2 months after electrocoagulation of &amp;lt;50% of the VIN3 lesions. She showed high frequency anti-E6 and anti-E7 effector blood T cells by ex vivo ELISpot-IFNγ assay before clinical regression. Immunohistochemical study of her vulvar biopsy revealed a marked dermal infiltrate containing a majority of CD4+ T lymphocytes and an epidermal infiltrate made up of both CD4+ and CD8+ T cells. This seems to be the first evidence of an association between spontaneous regression of VIN3 lesions and HPV-specific T-cell responses detectable in the blood. Hence, an increase of HPV-specific effector T lymphocyte responses by vaccine-based therapeutic strategies might be useful to clear the lesions in bowenoid papulosis disease.
Inhibitors of Brain Phospholipase A<sub>2</sub>Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders
Authors: Akhlaq A. Farooqui, Wei-Yi Ong, Lloyd A. Horrocks
Journal: Pharmacological Reviews (2006)

The phospholipase A<sub>2</sub> family includes secretory phospholipase A<sub>2</sub>, cytosolic phospholipase A<sub>2</sub>, plasmalogen-selective phospholipase A<sub>2</sub>, and calcium-independent phospholipase A<sub>2</sub>. It is generally thought that the release of arachidonic acid by cytosolic phospholipase A<sub>2</sub> is the rate-limiting step in the generation of eicosanoids and platelet activating factor. These lipid mediators play critical roles in the initiation and modulation of inflammation and oxidative stress. Neurological disorders, such as ischemia, spinal cord injury, Alzheimer9s disease, multiple sclerosis, prion diseases, and epilepsy are characterized by inflammatory reactions, oxidative stress, altered phospholipid metabolism, accumulation of lipid peroxides, and increased phospholipase A<sub>2</sub> activity. Increased activities of phospholipases A<sub>2</sub> and generation of lipid mediators may be involved in oxidative stress and neuroinflammation associated with the above neurological disorders. Several phospholipase A<sub>2</sub> inhibitors have been recently discovered and used for the treatment of ischemia and other neurological diseases in cell culture and animal models. At this time very little is known about in vivo neurochemical effects, mechanism of action, or toxicity of phospholipase A<sub>2</sub> inhibitors in human or animal models of neurological disorders. In kainic acid-mediated neurotoxicity, the activities of phospholipase A<sub>2</sub> isoforms and their immunoreactivities are markedly increased and phospholipase A<sub>2</sub> inhibitors, quinacrine and chloroquine, arachidonyl trifluoromethyl ketone, bromoenol lactone, cytidine 5-diphosphoamines, and vitamin E, not only inhibit phospholipase A<sub>2</sub> activity and immunoreactivity but also prevent neurodegeneration, suggesting that phospholipase A<sub>2</sub> is involved in the neurodegenerative process. This also suggests that phospholipase A<sub>2</sub> inhibitors can be used as neuroprotectants and anti-inflammatory agents against neurodegenerative processes in neurodegenerative diseases.