tbuckley/cabot-search huggingface dataset:
Prevalence of and Risk Factors for Peripheral Arterial Disease in the United States
Authors: Elizabeth Selvin, Thomas P. Erlinger
Journal: Circulation (2004)

Background— Peripheral arterial disease (PAD) is associated with significant morbidity and mortality and is an important marker of subclinical coronary heart disease. However, estimates of PAD prevalence in the general US population have varied widely. Methods and Results— We analyzed data from 2174 participants aged 40 years and older from the 1999–2000 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index &lt;0.90 in either leg. The prevalence of PAD among adults aged 40 years and over in the United States was 4.3% (95% CI 3.1% to 5.5%), which corresponds to ≈5 million individuals (95% CI 4 to 7 million). Among those aged 70 years or over, the prevalence was 14.5% (95% CI 10.8% to 18.2%). In age- and gender-adjusted logistic regression analyses, black race/ethnicity (OR 2.83, 95% CI 1.48 to 5.42) current smoking (OR 4.46, 95% CI 2.25 to 8.84), diabetes (OR 2.71, 95% CI 1.03 to 7.12), hypertension (OR 1.75, 95% CI 0.97 to 3.13), hypercholesterolemia (OR 1.68, 95% CI 1.09 to 2.57), and low kidney function (OR 2.00, 95% CI 1.08 to 3.70) were positively associated with prevalent PAD. More than 95% of persons with PAD had 1 or more cardiovascular disease risk factors. Elevated fibrinogen and C-reactive protein levels were also associated with PAD. Conclusions— This study provides nationally representative prevalence estimates of PAD in the United States, revealing that PAD affects more than 5 million adults. PAD prevalence increases dramatically with age and disproportionately affects blacks. The vast majority of individuals with PAD have 1 or more cardiovascular disease risk factors that should be targeted for therapy.
Disturbances of Glucose Metabolism in Men Referred for Coronary Arteriography
Authors: Irina Kowalska, Jolanta Prokop, Hanna Bachórzewska-Gajewska, Beata Telejko, Ida Kinalskal, Waclaw Kochman, Wlodzimierz Musial
Journal: Diabetes Care (2001)

OBJECTIVE—In some studies, fasting and postload glycemia are a strong predictor of coronary events and cardiac death. Therefore, we investigated the relationship between fasting and postload glucose concentrations and coronary status in 363 men referred for coronary arteriography without a previous history of diabetes. RESEARCH DESIGN AND METHODS—A total of 363 men (mean age 53.0 ± 9.1 years, mean BMI 27.9 ± 3.7 kg/m2) with positive results of exercise testing were included in the study. A standard oral glucose tolerance test (OGTT) with glucose and insulin estimations was performed on all subjects. The concentrations of total cholesterol, HDL cholesterol, triglycerides, and HbA1c were also measured. All patients were divided into four groups, according to coronary status: no changes in coronary arteries (group 0, n = 61), one-vessel disease (group I, n = 113), two-vessel disease (group II, n = 116), and three-vessel disease (group III, n = 73). RESULTS—The highest postload glucose concentrations were observed in group III. Also, insulin concentrations and HbA1c increased with the progression of atherosclerotic lesions in the coronary arteries. Based on results of the OGTT, 16% of the patients (n = 59) fulfilled the World Health Organization criteria for type 2 diabetes and 36% of the patients (n = 131) met criteria for impaired glucose tolerance. Significant correlations were observed between the number of involved vessels and postload glycemia, HbA1c, fasting insulin, and postload insulin. The multiple stepwise regression analysis showed that age, total cholesterol, and HDL cholesterol independently correlated with the number of involved vessels. CONCLUSIONS—We conclude that patients with advanced changes in the coronary arteries experience more pronounced metabolic disturbances. Postload glycemia could be an important predictor of nondiagnosed disturbances of glucose metabolism.
Genic Mutation Rates in Mammals: Local Similarity, Chromosomal Heterogeneity, and X-Versus-Autosome Disparity
Authors: C. M. Malcom
Journal: Molecular Biology and Evolution (2003)

The reduction of mutation rates on the mammalian X chromosome relative to autosomes is most often explained in the literature as evidence of male-driven evolution. This hypothesis attributes lowered mutation rates on the X chromosome to the fact that this chromosome spends less time in the germline of males than in the germline of females. In contrast to this majority view, two articles argued that the patterns of mutation rates across chromosomes are inconsistent with male-driven evolution. One article reported a 40% reduction in synonymous substitution rates (Ks) for X-linked genes relative to autosomes in the mouse-rat lineage. The authors argued that this reduction is too dramatic to be explained by male-driven evolution and concluded that selection has systematically reduced mutation rate on the X chromosome to a level optimal for this male-hemizygous chromosome. More recently, a second article found that chromosomal mutation rates in both the human-mouse and mouse-rat lineages were so heterogeneous that the X chromosome was not an outlier. Here again, the authors argued that this is at odds with male-driven evolution and suggested that selection has modulated chromosomal mutation rates to locally optimal levels, thus extending the argument of the first mentioned article to include autosomes. Here, we reexamine these conclusions using mouse-rat and human-mouse coding-region data. We find a more modest reduction of Ks on the X chromosome, but our results contradict the finding that the X chromosome is not distinct from autosomes. Multiple statistical tests show that Ks rates on the X chromosome differ systematically from the autosomes in both lineages. We conclude that the moderate reduction of mutation rate on the X chromosome of both lineages is consistent with male-driven evolution; however, the large variance in mutation rates across chromosomes suggests that mutation rates are affected by additional factors besides male-driven evolution. Investigation of mutation rates by synteny reveals that synteny blocks, rather than entire chromosomes, might represent the unit of mutation rate variation.
Effect of nitroglycerin and dipyridamole on regional left ventricular blood flow during coronary artery occlusion.
Authors: L C Becker
Journal: Journal of Clinical Investigation (1976)

Coronary vasodilators have been variously reported to increase, decrease, or have no effect upon blood flow to ischemic myocardium. Consequently, the effects of two different types of dilators, nitroglycerin (TNG) and dipyridamole, were studied with radioactive microspheres in open-chested dogs after coronary artery ligation. Given as a bolus i.v. injection 0.4 mg TNG resulted in an increase in blood flow to nonischemic areas of myocardium and a preservation of flow to ischemic regions, despite a fall in blood pressure. 5 min later blood pressure and nonischemic flow were back to base line, and a small selective increase in flow to ischemic myocardium was found (0.15-0.18 ml/min per g, P less than 0.05). During an 0.2 mg/min infusion of TNG, and also after 1 mg/kg i.v. dipyridamole, ischemic flow was maintained in the face of a 20-30% reduction in blood pressure. In this setting, nonischemic flow was unchanged during TNG and doubled after dipyridamole. With the addition of methoxamine in both dilator groups, blood pressure returned to base line while flow to ischemic areas increased above base-line values (TNG, 0.16-0.20 ml/min per g, P less than 0.01; dipyridamole, 0.18-0.31 ml/min per g, P less than 0.05). Epicardial ST segment elevations increased during TNG infusion and were unchanged after dipyridamole, but with addition of methoxamine, ST segments became less elevated in both drug groups, concomitant with the observed increase in collateral blood flow. These data indicate that both types of coronary vasodilators, when used in conjunction with methoxamine to support blood pressure, reduce collateral resistance, increase collateral flow, and reduce epicardial ST-segment elevations.
Partial rupture of the proximal Achilles tendon: a differential diagnostic problem in ultrasound imaging
Authors: R Kayser, K Mahlfeld, C E Heyde
Journal: British Journal of Sports Medicine (2005)

Objectives: The aim of this study was to determine whether ultrasound can correctly visualise partial ruptures of the proximal Achilles tendon. Method: This was a prospective study in which all chronic Achilles tendon injury patients seen at three centres in Germany from 1998 to 2003 were screened. All patients with clinical and/or sonographic signs of abnormalities in the region of the proximal third of the Achilles tendon and tendomuscular junction were included in the analysis. Each of these cases was evaluated by ultrasound following an assessment protocol. Patients with ambiguous ultrasound findings and/or clinical signs were additionally assessed by magnetic resonance imaging (MRI). Results: Sonomorphologic changes suggestive of an abnormality in the proximal third of the Achilles tendon were detected in 13 out of 320 patients (4.2%) with recurring Achilles tendon complaints. Thirteen patients had clinical signs but no sonographic changes in the tendon. The sonographic diagnosis was correct in 19 cases. In six of the 26 cases studied, MRI was needed to establish the correct diagnosis of partial intratendinous rupture of the proximal Achilles tendon. Sensitivity was 0.5, specificity was 0.81, and the overall agreement of the ultrasound examination was 61.5%. All patients were asymptomatic at follow up at a mean of 14 months (range 12–17 months) after surgery. Conclusions: Ultrasound is a useful tool for evaluation of proximal Achilles tendon complaints. However, ultrasound is not sufficiently reliable for diagnosis of all pathologies, especially partial ruptures of the Achilles tendon. Thus, the definitive diagnosis must be established by MRI.
Lymphocyte Cc Chemokine Receptor 9 and Epithelial Thymus-Expressed Chemokine (Teck) Expression Distinguish the Small Intestinal Immune Compartment
Authors: Eric J. Kunkel, James J. Campbell, Guttorm Haraldsen, Junliang Pan, Judie Boisvert, Arthur I. Roberts, Ellen C. Ebert, Mark A. Vierra, Stuart B. Goodman, Mark C. Genovese, Andy J. Wardlaw, Harry B. Greenberg, Christina M. Parker, Eugene C. Butcher, David P. Andrew, William W. Agace
Journal: The Journal of Experimental Medicine (2000)

The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4+ and CD8+ T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9+, and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9−. TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.
Anti-VEGF Antibodies Mitigate the Development of Radiation Necrosis in Mouse Brain
Authors: Xiaoyu Jiang, John A. Engelbach, Liya Yuan, Jeremy Cates, Feng Gao, Robert E. Drzymala, Dennis E. Hallahan, Keith M. Rich, Robert E. Schmidt, Joseph J.H. Ackerman, Joel R. Garbow
Journal: Clinical Cancer Research (2014)

Abstract Purpose: To quantify the effectiveness of anti-VEGF antibodies (bevacizumab and B20-4.1.1) as mitigators of radiation-induced, central nervous system (brain) necrosis in a mouse model. Experimental Design: Cohorts of mice were irradiated with single-fraction 50- or 60-Gy doses of radiation targeted to the left hemisphere (brain) using the Leksell Perfexion Gamma Knife. The onset and progression of radiation necrosis were monitored longitudinally by in vivo, small-animal MRI, beginning 4 weeks after irradiation. MRI-derived necrotic volumes for antibody (Ab)-treated and untreated mice were compared. MRI results were supported by correlative histology. Results: Hematoxylin and eosin–stained sections of brains from irradiated, non–Ab-treated mice confirmed profound tissue damage, including regions of fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, loss of neurons, and edema. Treatment with the murine anti-VEGF antibody B20-4.1.1 mitigated radiation-induced changes in an extraordinary, highly statistically significant manner. The development of radiation necrosis in mice under treatment with bevacizumab (a humanized anti-VEGF antibody) was intermediate between that for B20-4.1.1–treated and non–Ab-treated animals. MRI findings were validated by histologic assessment, which confirmed that anti-VEGF antibody treatment dramatically reduced late-onset necrosis in irradiated brain. Conclusions: The single-hemispheric irradiation mouse model, with longitudinal MRI monitoring, provides a powerful platform for studying the onset and progression of radiation necrosis and for developing and testing new therapies. The observation that anti-VEGF antibodies are effective mitigants of necrosis in our mouse model will enable a wide variety of studies aimed at dose optimization and timing and mechanism of action with direct relevance to ongoing clinical trials of bevacizumab as a treatment for radiation necrosis. Clin Cancer Res; 20(10); 2695–702. ©2014 AACR.
Efficacy of bispectral index monitoring as an adjunct to propofol deep sedation for ERCP: a randomized controlled trial
Authors: G. Paspatis, I. Chainaki, M. Manolaraki, E. Vardas, A. Theodoropoulou, G. Tribonias, K. Konstantinidis, K. Karmiris, G. Chlouverakis
Journal: Endoscopy (2009)

Background and study aims: We sought to determine whether bispectral index (BIS) monitoring is a useful adjunct to the administration of propofol titrated to deep sedation, as measured by reductions of doses of propofol administered during endoscopic retrograde cholangiopancreatography (ERCP).
Recent developments in atrial fibrillation
Authors: M Bilal Iqbal, Anil K Taneja, Gregory Y H Lip, Marcus Flather
Journal: BMJ (2005)

Atrial fibrillation, the most commonly encountered arrhythmia in clinical practice, is associated with substantial morbidity and mortality. Its incidence and prevalence are increasing, and it represents a growing clinical and economic burden. Recent research has highlighted new approaches to both pharmacological and non-pharmacological management strategies. Clinicians need to have a sound working knowledge of atrial fibrillation and to be up to date with the emerging evidence to guide treatment and improve outcomes in these patients.

In this article, we highlight the recent advances in atrial fibrillation. We searched PubMed/Medline, Embase, and Cochrane databases by using the keywords “atrial fibrillation,” “rate,” “rhythm,” “anticoagulation,” and “non-pharmacological.” We also searched references of recent major articles and key reviews, and we obtained articles where necessary.

Atrial fibrillation affects an estimated 2.2 million adults in the United States.1 In the United Kingdom alone, more than 46 000 new cases of atrial fibrillation are diagnosed every year.2 The prevalence of atrial fibrillation doubles with each advancing decade from the age of 50.3 Independent risk factors include male sex, increasing age, hypertension, diabetes, smoking, valvular heart disease, and myocardial infarction.4 Left atrial dilatation, left ventricular hypertrophy, and impaired left ventricular systolic function are also associated with atrial fibrillation.5 Compared with people in sinus rhythm, those in atrial fibrillation have a sixfold increased risk of stroke and twofold increased risk of death. For those with rheumatic heart disease, the risk of stroke is increased up to 18-fold.6

The nomenclature used to classify atrial fibrillation has been diverse. Recent guidelines recommend a classification system based on the temporal pattern of the arrhythmia (fig 1).7



Fig 1 
Classification of atrial fibrillation.*When a patient has had two or more episodes of atrial fibrillation, this is termed recurrent. Both paroxysmal and persistent atrial fibrillation …
Comparative genomic analysis of mouse and human mammary tumors
Authors: Charles M Perou
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
Bronchial responsiveness, lung mechanics, gas transfer, and corticosteroid response in patients with chronic airflow obstruction.
Authors: A L James, K E Finucane, G Ryan, A W Musk
Journal: Thorax (1988)

Thirty patients with stable chronic airflow obstruction receiving regular bronchodilator treatment were studied to determine whether the level of bronchial responsiveness, transfer factor for carbon monoxide (TLCO), or the mechanical properties of the lung predicted a bronchodilator response to oral corticosteroid treatment. Before treatment mean (SD) FEV1 was 48% (16%) of the predicted value (% pred); the geometric mean concentration of methacholine required to produce a 20% fall in FEV1 (PC20) was 0.44 (range 0.07-3.32) mg/ml; and TLCO was 59% (21%) predicted. The exponential constant (k) defining the shape of the static volume-pressure curve was 146% (66%) predicted and pulmonary conductance relative to predicted lung volume at a transpulmonary pressure of 5 cm H2O (sGL5) was 72% (37%) predicted. After prednisolone treatment (0.6 mg kg-1 day-1 for two weeks) FEV1 increased by 8% (19%) (p less than 0.05) and daily mean peak flow (PEF) by 3% (10%) (p less than 0.01) over pretreatment values. Three patients had an increase in FEV1 of more than 30%, two of whom had sputum eosinophilia (p less than 0.05). The three were among the 13 patients with a reduced sGL5. The increase in FEV1 did not correlate with initial PC20 (r = 0.16), k (r = -0.12), or TLCO (r = -0.14). Thus measurements of bronchial responsiveness, lung distensibility, and TLCO did not predict corticosteroid response in patients with stable chronic airflow obstruction. Patients with sputum eosinophilia or reduced pulmonary conductance may be more likely to respond.
Influence of Doxorubicin Dose Intensity on Response and Outcome for Patients With Osteogenic Sarcoma and Ewing's Sarcoma
Authors: M. A. Smith, R. S. Ungerleider, M. E. Horowitz, R. Simon
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Influence of Doxorubicin Dose Intensity on Response and Outcome for Patients With Osteogenic Sarcoma and Ewing's Sarcoma Get access Malcolm A. Smith, Malcolm A. Smith * Cancer Therapy Evaluation Program, Division of Cancer Treatment, National Cancer InstituteBethesda, Md.Pediatric Branch, Division of Cancer Treatment, National Cancer Institute. * Correrspondence to: Malcolm A. Smith, M.D., Cancer Therapy Evaluation Program, National Institutes of Health, Executive Plaza North, Rm. 741, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard S. Ungerleider, Richard S. Ungerleider Cancer Therapy Evaluation Program, Division of Cancer Treatment, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Marc E. Horowitz, Marc E. Horowitz Pediatric Branch, Division of Cancer Treatment, National Cancer Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Simon Richard Simon Cancer Therapy Evaluation Program, Division of Cancer Treatment, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 20, 16 October 1991, Pages 1460–1470, https://doi.org/10.1093/jnci/83.20.1460 Published: 16 October 1991 Article history Received: 29 April 1991 Revision received: 08 July 1991 Accepted: 12 July 1991 Published: 16 October 1991
Sleep {middle dot} 2: Pathophysiology of obstructive sleep apnoea/hypopnoea syndrome
Authors: R B Fogel
Journal: Thorax (2004)

The pathogenesis of airway obstruction in patients with obstructive sleep apnoea/hypopnoea syndrome is reviewed. The primary defect is probably an anatomically small or collapsible pharyngeal airway, in combination with a sleep induced fall in upper airway muscle activity.