tbuckley/cabot-search huggingface dataset:
Effects of alcohol use and other aspects of lifestyle on blood pressure levels and prevalence of hypertension in a working population.
Authors: P D Arkwright, L J Beilin, I Rouse, B K Armstrong, R Vandongen
Journal: Circulation (1982)

The relationship between alcohol consumption and blood pressure was studied in 491 males, ages 20-45 years, who volunteered to complete a health questionnaire and submit to standardized measurements of blood pressure, heart rate and body size. Average weekly alcohol consumption correlated with systolic pressure (r = 0.18) but not diastolic pressure. Systolic pressure increased progressively with increasing alcohol consumption, with no obvious threshold effect. In moderate and heavy drinkers (53% of the population studied), the prevalence of systolic hypertension (greater than or equal to 140 mm Hg) was four times that of teetotalers. The effect of alcohol on systolic blood pressure was independent of the effects of age, obesity, cigarette smoking and physical activity. Ex-heavy drinkers had blood pressures similar to those of teetotalers, suggesting that the effect of alcohol is reversible. Cigarette smokers had lower diastolic pressures than nonsmokers, an effect independent of obesity. The linear correlation between alcohol consumption and systolic blood pressure and the lower blood pressures in exdrinkers suggest a cause-and-effect relationship. The results indicate that alcohol ranks close to obesity as a potentially preventable cause of hypertension in the community.
Radiosensitization With Carboplatin for Patients With Unresectable Stage III Non–Small-Cell Lung Cancer: A Phase III Trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group
Authors: Gerald Clamon, James Herndon, Robert Cooper, Alex Y. Chang, Julian Rosenman, Mark R. Green
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine whether the administration of carboplatin concurrently with radiation treatment improves survival in patients with inoperable stage III non–small-cell lung cancer. PATIENTS AND METHODS: Two hundred eighty-three patients with inoperable stage III non–small-cell lung cancer were entered onto a randomized trial by the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. Randomization was performed before initiation of any therapy. All patients received an induction chemotherapy program with vinblastine and cisplatin for 5 weeks, followed by 6,000 cGy of radiation therapy over 6 weeks. One hundred thirty-seven patients were randomized to this therapy regimen alone; 146 patients were randomized to receive carboplatin at 100 mg/m 2 /wk concurrent with the radiation therapy. RESULTS: The complete response was 18% with concurrent carboplatin versus 10% with radiotherapy alone (P = .101). There was no difference with respect to failure-free survival (10% with carboplatin and 9% with radiotherapy alone) or overall survival (13% with carboplatin and 10% with radiotherapy alone) at 4 years. In patients not receiving carboplatin, the relapse rate was 69% within the field of radiation and 53% in the boost volume. In patients receiving carboplatin, the relapse rate was 59% within the field of radiation and 43% in the boost volume. Patients with cancers more than 70 cm 2 in size had significantly poorer survival (P = .01) CONCLUSION: Carboplatin at the dose and schedule used did not significantly impact on disease control or survival. The relapse rate within the chest remained more than 50%. More effective regimens will be required to impact on local disease control and survival.
Yersinia specific immune complexes in the synovial fluid of patients with yersinia triggered reactive arthritis.
Authors: R Lahesmaa-Rantala, K Granfors, H Isomaki, A Toivanen
Journal: Annals of the Rheumatic Diseases (1987)

Yersinia specific immune complexes were demonstrated in the synovial fluid of three patients out of 12 with yersinia triggered reactive arthritis. They were not detectable in the synovial fluid of any of the 16 control patients, including nine with reactive arthritis triggered by factors other than yersiniae. Platelet reactive IgG was detectable in the synovial fluid of eight out of the 12 patients with yersinia triggered reactive arthritis and in three of the 16 control patients, all three having rheumatoid arthritis. An enzyme linked immunosorbent assay and a platelet 125I labelled staphylococcal protein A test were used to measure yersinia specific immune complexes and platelet reactive IgG respectively. The results obtained show for the first time the occurrence of bacterial antigens, derived from the causative strain, in the synovial fluid in yersinia triggered reactive arthritis.
2010: the Year of the Lung
Authors: N. M. Siafakas, M. Decramer, K. F. Rabe
Journal: European Respiratory Journal (2010)

Pulmonologists and respiratory scientists believe that respiratory health and disease are neglected by the public, politicians and the health policy makers in the world 1. We may be biased 2 but the numbers are strongly in support of this opening statement. One example is the funding for respiratory research which is inadequate. In the UK in 2002 respiratory research only claimed 2.8% of the Medical Research Council budget, while 13% of mortality was due to respiratory disease 3. Similar estimations have been made in other countries. The global prevalence of respiratory disease also supports this statement. In a recent estimate, the World Health Organization (WHO) considers respiratory diseases to be the second leading cause of death after cardiovascular diseases. In addition, mortality from cardiovascular diseases is decreasing in prevalence but mortality from lung diseases is on the rise 4. For example, chronic obstructive pulmonary disease (COPD) will become the third cause of death in the world by the year 2020, from the sixth position on the mortality scale in 1990 5. Adding up the prevalence of all respiratory diseases (asthma, COPD, lung cancer, tuberculosis, pneumonias and sleep-disordered breathing among others) shows that almost a billion people worldwide are struggling to breathe and that almost 12 million will die each year as a result. Although lung diseases affect people in every country, the poor, the old, the young and the weak are …
Children at high altitude have less nocturnal periodic breathing than adults
Authors: M. Kohler, S. Kriemler, E. M. Wilhelm, H. Brunner-LaRocca, M. Zehnder, K. E. Bloch
Journal: European Respiratory Journal (2008)

Although children commonly travel to high altitudes, their respiratory adaptation to hypoxia remains elusive. Therefore, in the present study respiratory inductive plethysmography, pulse oximetry (<i>S</i><sub>p,O<sub>2</sub></sub>) and end-tidal CO<sub>2</sub> tension (<i>P</i><sub>ET,CO<sub>2</sub></sub>) were recorded in 20 pre-pubertal children (aged 9–12 yrs) and their fathers during 1 night in Zurich (490 m) and 2 nights at the Swiss Jungfrau-Joch research station (3,450 m) following ascent by train within &lt;3 h. In children, mean±sd nocturnal <i>S</i><sub>p,O<sub>2</sub></sub> fell from 98±1% at 490 m to 85±4 and 86±4% at 3,450 m (nights 1 and 2, respectively); <i>P</i><sub>ET,CO<sub>2</sub></sub>decreased significantly from 37±6 to 32±3 and 33±4 mmHg (3,450 <i>versus</i> 490 m). In adults, changes in nocturnal <i>S</i><sub>p,O<sub>2</sub></sub> and <i>P</i><sub>ET,CO<sub>2</sub></sub>at 3,450 m were similar to those in children. Children spent less time in periodic breathing at 3,450 m during night 1 and 2 (8±11 and 9±13%, respectively) than adults (34±24 and 22±17%, respectively), and their apnoea threshold for CO<sub>2</sub> was lower compared with adults (27±2 and 30±2 mmHg, respectively, both nights). <i>S</i><sub>p,O<sub>2</sub></sub>, <i>P</i><sub>ET,CO<sub>2</sub></sub> and time in periodic breathing at altitude were not correlated between children and their fathers. In conclusion, children revealed a similarly reduced nocturnal O<sub>2</sub> saturation and associated hyperventilation at high altitude as adults but their breathing pattern was more stable, possibly related to a lower apnoea threshold for CO<sub>2</sub>.
A Randomized Trial to Assess Catheter Ablation Versus Rate Control in the Management of Persistent Atrial Fibrillation in Heart Failure
Authors: David G. Jones, Shouvik K. Haldar, Wajid Hussain, Rakesh Sharma, Darrel P. Francis, Shelley L. Rahman-Haley, Theresa A. McDonagh, S. Richard Underwood, Vias Markides, Tom Wong
Journal: Journal of the American College of Cardiology (2013)
Prospective Study of Neuropeptide Y as an Adverse Cardiovascular Risk Factor in End-Stage Renal Disease
Authors: Carmine Zoccali, Francesca Mallamaci, Giovanni Tripepi, Francesco A. Benedetto, Saverio Parlongo, Sebastiano Cutrupi, Domenico Iellamo, Graziella Bonanno, Francesco Rapisarda, Pasquale Fatuzzo, Giuseppe Seminara, Alessandro Cataliotti, Lorenzo Salvatore Malatino
Journal: Journal of the American Society of Nephrology (2003)

Chronic renal insufficiency is a situation characterized by high plasma concentration of neuropeptide Y (NPY). Because this neuropeptide interferes with cardiovascular (CV) function, it is possible that it is involved in the high CV-related morbidity and mortality of these patients. To test this hypothesis, a follow-up study was performed (average duration, 34 mo; range 0.2 to 52.0 mo) in a cohort of 277 patients with end-stage renal disease receiving chronic dialysis. Univariate analysis revealed that plasma NPY was directly related to plasma norepinephrine (r = 0.37, P < 0.001) and epinephrine (r = 0.17, P = 0.005), exceeding the upper limit of the normal range in the majority of patients with end-stage renal disease (170 of 277, 61%). One hundred thirteen patients had one or more fatal and nonfatal CV events; 112 patients died, 66 of them (59%) of CV causes. Plasma NPY failed to predict all-cause mortality but was an independent predictor of adverse CV outcomes (hazard ratio [10 pmol/L increase in plasma NPY], 1.32; 95% confidence interval, 1.09 to 1.60; P = 0.004) in a Cox proportional-hazard model that included a series of traditional and nontraditional CV risk factors. Plasma NPY maintained its predictive power for CV events in statistical model including plasma norepinephrine. Plasma NPY predicts incident CV complications in end-stage renal disease. Controlled trials are needed to establish whether interference with the sympathetic system, NPY, or both may reduce the high CV morbidity and mortality of dialysis patients.
Phase I Pharmacokinetic and Biologic Correlative Study of Mapatumumab, a Fully Human Monoclonal Antibody With Agonist Activity to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Receptor-1
Authors: Anthony W. Tolcher, Monica Mita, Neal J. Meropol, Margaret von Mehren, Amita Patnaik, Kristin Padavic, Monique Hill, Theresa Mays, Therese McCoy, Norma Lynn Fox, Wendy Halpern, Alfred Corey, Roger B. Cohen
Journal: Journal of Clinical Oncology (2007)

Purpose To assess the safety, pharmacokinetics, and preliminary evidence of antitumor activity of mapatumumab (HGS-ETR1, TRM-1), a fully human agonist monoclonal antibody directed to the tumor necrosis factor–related apoptosis-inducing ligand receptor-1 (TRAIL-R1). Patients and Methods Patients with advanced solid malignancies were treated with escalating doses of mapatumumab intravenously (IV) administered over 30 to 120 minutes, initially as a single dose and then repetitively. Plasma mapatumumab concentrations were measured and serum was assayed to detect human antimapatumumab antibody formation. Archival tumor specimens were collected to detect the presence of TRAIL-R1 by immunohistochemistry. Results Forty-nine patients received 158 courses at doses ranging from 0.01 to 10 mg/kg IV. Initially, patients received mapatumumab as a single dose, then every 28 days repetitively, and then 10 mg/kg every 14 days. Mild (grade 1 or 2) fatigue, fever, and myalgia were the most frequently reported nonhematologic adverse events related to mapatumumab, whereas hematologic toxicity was not clinically significant. The mean (± standard deviation) clearance and terminal elimination half-life values for mapatumumab at 10 mg/kg every 14 days were 3.7 mL/d/kg (± 1.5 mL/d/kg) and 18.8 days (± 10.1 days), respectively. TRAIL-R1 was documented in 68% of patients' tumors assayed. Nineteen patients had stable disease, with two lasting 9 months. Conclusion Mapatumumab can be administered safely and feasibly at 10 mg/kg IV every 14 days. The absence of severe toxicities and the attainment of plasma mapatumumab concentrations that are active in preclinical models warrant further disease-directed studies of this agent alone and in combination with chemotherapy in a broad array of tumors.
Deficit of Somatostatin-Like Immunoreactivity in the Vitreous Fluid of Diabetic Patients
Authors: Rafael Simó, Albert Lecube, Laura Sararols, José García-Arumí, Rosa M. Segura, Roser Casamitjana, Cristina Hernández
Journal: Diabetes Care (2002)

OBJECTIVE—To evaluate the vitreous levels of somatostatin-like immunoreactivity (SLI) in patients with proliferative diabetic retinopathy (PDR). RESEARCH DESIGN AND METHODS—A total of 14 diabetic patients with PDR, in whom a vitrectomy was performed, were included in the study. Sixteen nondiabetic patients, with other conditions requiring vitrectomy, served as a control group. Both venous blood and vitreous samples were collected at the time of vitreoretinal surgery. Patients in whom intravitreous hemoglobin was detectable were excluded. In addition, a correction for plasma levels of SLI and intravitreal proteins was performed. SLI was measured by radioimmunoassay and vitreous hemoglobin by spectrophotometry. RESULTS—SLI in the vitreous fluid was significantly lower in diabetic patients than in the control group (68 ± 18.7 vs. 193.6 ± 30.8 pg/ml, P &amp;lt; 0.01). The vitreous SLI-to-plasma SLI ratio was strikingly higher in nondiabetic subjects than in diabetic patients with PDR (5.3 [1.2–71.1] vs. 0.6 [0.03–4.1], P &amp;lt; 0.01). After correcting for total vitreous protein concentration, SLI (pg/mg of proteins) remained significantly higher in nondiabetic control subjects than in diabetic patients with PDR (186 [51–463] vs. 7.5 [0.8–82], P &amp;lt; 0.0001). Remarkably, intravitreous levels of SLI were higher than those obtained in plasma in nondiabetic control subjects (193.6 ± 30.8 vs. 43.5 ± 10.7 pg/ml, P &amp;lt; 0.0001). Finally, a lack of relationship between plasma and vitreous levels of SLI was observed in both diabetic patients with PDR and nondiabetic control subjects. CONCLUSIONS—The significantly higher SLI in the vitreous fluid than in plasma detected in nondiabetic control subjects supports the concept that somatostatin plays a relevant role in retinal homeostasis. In addition, the intravitreous deficit of SLI observed in diabetic patients with PDR suggests that it might contribute to the process of retinal neovascularization.
Combinations of Polymorphisms in Genes Involved in the 5-Fluorouracil Metabolism Pathway Are Associated with Gastrointestinal Toxicity in Chemotherapy-Treated Colorectal Cancer Patients
Authors: Shoaib Afzal, Milena Gusella, Ben Vainer, Ulla B. Vogel, Jon T. Andersen, Kasper Broedbaek, Morten Petersen, Espen Jimenez-Solem, Laura Bertolaso, Carmen Barile, Roberto Padrini, Felice Pasini, Søren A. Jensen, Henrik E. Poulsen
Journal: Clinical Cancer Research (2011)

The purpose of this study was to investigate whether specific combinations of polymorphisms in genes encoding proteins involved in 5-fluorouracil (5-FU) pharmacokinetics and pharmacodynamics are associated with increased risk of treatment-induced toxicity.We analyzed two cohorts of 161 and 340 patients, the exploration and validation cohort, respectively. All patients were treated similarly with 5-FU-based adjuvant chemotherapy. We analyzed 13 functional polymorphisms and applied a four-fold analysis strategy using individual polymorphisms, haplotypes, and phenotypic enzyme activity or expression classifications based on combinations of functional polymorphisms in specific genes. Furthermore, multifactor dimensionality reduction analysis was used to identify a genetic interaction profile indicating an increased risk of toxicity.Alleles associated with low activity of methylene tetrahydrofolate reductase (MTHFR) were associated with decreased risk of toxicity [OR(Exploration) 0.39 (95% CI: 0.21-0.71, P = 0.003), OR(Validation) 0.63 (95% CI: 0.41-0.95, P = 0.03)]. A specific combination of the MTHFR 1298A>C and thymidylate synthase (TYMS) 3'-UTR (untranslated region) ins/del polymorphisms was significantly associated with increased toxicity in both cohorts [OR(Exploration) 2.40 (95% CI: 1.33-4.29, P = 0.003), OR(Validation) 1.81 (95% CI: 1.18-2.79, P = 0.007)]. The specific combination was also associated with increased cumulative incidence and earlier occurrence of severe toxicity during treatment.Our results indicate that MTHFR activity and a specific combination of the MTHFR 1298A>C and TYMS 3'-UTR ins/del polymorphisms are possible predictors of 5-FU treatment-related toxicity.
Efficacy and Safety of the Human Glucagon-Like Peptide-1 Analog Liraglutide in Combination With Metformin and Thiazolidinedione in Patients With Type 2 Diabetes (LEAD-4 Met+TZD)
Authors: Bernard Zinman, John Gerich, John B. Buse, Andrew Lewin, Sherwyn Schwartz, Philip Raskin, Paula M. Hale, Milan Zdravkovic, Lawrence Blonde
Journal: Diabetes Care (2009)

OBJECTIVE To determine the efficacy and safety of liraglutide (a glucagon-like peptide-1 receptor agonist) when added to metformin and rosiglitazone in type 2 diabetes. RESEARCH DESIGN AND METHODS This 26-week, double-blind, placebo-controlled, parallel-group trial randomized 533 subjects (1:1:1) to once-daily liraglutide (1.2 or 1.8 mg) or liraglutide placebo in combination with metformin (1 g twice daily) and rosiglitazone (4 mg twice daily). Subjects had type 2 diabetes, A1C 7–11% (previous oral antidiabetes drug [OAD] monotherapy ≥3 months) or 7–10% (previous OAD combination therapy ≥3 months), and BMI ≤45 kg/m2. RESULTS Mean A1C values decreased significantly more in the liraglutide groups versus placebo (mean ± SE −1.5 ± 0.1% for both 1.2 and 1.8 mg liraglutide and −0.5 ± 0.1% for placebo). Fasting plasma glucose decreased by 40, 44, and 8 mg/dl for 1.2 and 1.8 mg and placebo, respectively, and 90-min postprandial glucose decreased by 47, 49, and 14 mg/dl, respectively (P &amp;lt; 0.001 for all liraglutide groups vs. placebo). Dose-dependent weight loss occurred with 1.2 and 1.8 mg liraglutide (1.0 ± 0.3 and 2.0 ± 0.3 kg, respectively) (P &amp;lt; 0.0001) compared with weight gain with placebo (0.6 ± 0.3 kg). Systolic blood pressure decreased by 6.7, 5.6, and 1.1 mmHg with 1.2 and 1.8 mg liraglutide and placebo, respectively. Significant increases in C-peptide and homeostasis model assessment of β-cell function and significant decreases in the proinsulin-to-insulin ratio occurred with liraglutide versus placebo. Minor hypoglycemia occurred more frequently with liraglutide, but there was no major hypoglycemia. Gastrointestinal adverse events were more common with liraglutide, but most occurred early and were transient. CONCLUSIONS Liraglutide combined with metformin and a thiazolidinedione is a well-tolerated combination therapy for type 2 diabetes, providing significant improvements in glycemic control.
The G-Quadruplex-Interactive Molecule BRACO-19 Inhibits Tumor Growth, Consistent with Telomere Targeting and Interference with Telomerase Function
Authors: Angelika M. Burger, Fangping Dai, Christoph M. Schultes, Anthony P. Reszka, Michael J. Moore, John A. Double, Stephen Neidle
Journal: Cancer Research (2005)

Abstract Interference with telomerase and telomere maintenance is emerging as an attractive target for anticancer therapies. Ligand-induced stabilization of G-quadruplex formation by the telomeric DNA single-stranded 3′ overhang inhibits telomerase from catalyzing telomeric DNA synthesis and from capping telomeric ends. We report here the effects of a 3,6,9-trisubstituted acridine compound, BRACO-19, on telomerase function in vitro and in vivo. The biological activity of BRACO-19 was evaluated in the human uterus carcinoma cell line UXF1138L, which has very short telomeres (2.7 kb). In vitro, nuclear human telomerase reverse transcriptase (hTERT) expression was drastically decreased after 24 hours, induction of cellular senescence and complete cessation of growth was seen after 15 days, paralleled by telomere shortening of ca. 0.4 kb. In vivo, BRACO-19 was highly active as a single agent against early-stage (68 mm3) tumors in a s.c. growing xenograft model established from UXF1138L cells, if given chronically at 2 mg per kg per day i.p. BRACO-19 produced growth inhibition of 96% compared with controls accompanied by partial regressions (P &amp;lt; 0.018). Immunostaining of xenograft tissues showed that this response was paralleled by loss of nuclear hTERT protein expression and an increase in atypical mitoses indicative of telomere dysfunction. Cytoplasmic hTERT expression and its colocalization with ubiquitin was observed suggesting that hTERT is bound to ubiquitin and targeted for enhanced degradation upon BRACO-19 treatment. This is in accord with a model of induced displacement of telomerase from the telomere. The in vitro and in vivo data presented here is consistent with the G-quadruplex binding ligand BRACO-19 producing an anticancer effect by inhibiting the capping and catalytic functions of telomerase.
Effect of antibody to transforming growth factor beta on bleomycin induced accumulation of lung collagen in mice.
Authors: S N Giri, D M Hyde, M A Hollinger
Journal: Thorax (1993)

BACKGROUND--Increased production of transforming growth factor beta (TGF-beta) seems to have an important role in the pathophysiology of bleomycin induced lung fibrosis. This is attributed to the ability of TGF-beta to stimulate infiltration of inflammatory cells and promote synthesis of connective tissue, leading to collagen deposition. METHODS--The study was designed to evaluate the antifibrotic potential of TGF-beta antibody in mice treated with bleomycin, which is a model of lung fibrosis. Under methoxyflurane anaesthesia, each mouse received intratracheally either 50 microliters sterile isotonic saline or 0.125 units bleomycin in 50 microliters. Within five minutes after the instillation, mice received into the tail vein 100 microliters non-immune rabbit IgG, TGF-beta 2 antibody, or a combination of TGF-beta 2 and TGF-beta 1 antibodies at various dose regimens. Mice were killed 14 days after the instillation and their lungs processed for morphological and biochemical studies. RESULTS--Administration of 250 micrograms of TGF-beta 2 antibody after instillation of bleomycin followed by 100 micrograms on day 5 and 100 micrograms on day 9 significantly reduced the bleomycin induced increases in the accumulation of lung collagen from 445.8 (42.3) micrograms/lung to 336.7 (56.6) micrograms/lung at 14 days. Similarly, the combined treatment with 250 micrograms TGF-beta 2 antibody and 250 micrograms TGF-beta 1 antibody after bleomycin instillation followed by 100 micrograms of each antibody on day 5 also caused a significant reduction in bleomycin induced increases in lung collagen accumulation and myeloperoxidase activity at 14 days. CONCLUSIONS--These results suggest that TGF-beta has an important role in the aetiology of bleomycin induced lung fibrosis; the neutralisation of TGF-beta by systemic treatment with its antibodies offers a new mode of pharmacological intervention which may be useful in treating lung fibrosis.