tbuckley/cabot-search huggingface dataset:
Prostaglandins mediate bradykinin-induced reduction of exhaled nitric oxide in asthma
Authors: SA Kharitonov, MM Sapienza, KF Chung, PJ Barnes
Journal: European Respiratory Journal (1999)

Bradykinin (BK) is a mediator of inflammation in asthma with potent bronchoconstrictor actions. Endogenous release of nitric oxide may inhibit BK-induced bronchoconstriction. This study investigated whether bradykinin inhalation could modulate exhaled NO levels in normal and asthmatic subjects, and whether the bradykinin-induced effects were mediated through the production of cyclo-oxygenase products in patients with asthma, by studying the effect of the cyclo-oxygenase inhibitor, L-acetylsalicylic acid (L-ASA). Exhaled NO concentration and forced expiratory volume in one second (FEV1) were measured by chemiluminescence following inhalation of increasing concentrations of BK. In asthmatics (n=11), BK induced a dose-dependent decrease in exhaled NO concentration from 21.3+/-1.6 to 6.+/-0.5 parts per billion (ppb) (p&lt;0.01) at the highest concentration, associated with a significant fall in FEV1. In normal subjects (n=10), the exhaled NO concentration fell from 7.2+/-0.13 to 4.3+/-0.51 ppb (p&lt;0.001) 15 min, after a single inhalation of BK, but without a significant change in FEV1. In asthmatic subjects, pretreatment with inhaled L-ASA (90 x mg x mL(-1), 4 mL) did not alter exhaled NO levels, but prevented a BK-induced fall in exhaled NO concentration, as indicated by a significant increase in exhaled NO levels at the provocative concentration of BK causing a 20% fall in FEV1, (5.7 +/- 0.94 ppb after placebo and 12.0 +/- 1.8 ppb after L-ASA; p&lt;0.05). L-ASA significantly reduced bronchial responsiveness to BK 3.9-fold (p&lt;0.01). Inhaled bradykinin induced bronchoconstriction and a reduction in exhaled nitric oxide levels in asthmatic subjects, an effect that is partly mediated by cyclo-oxygenase products.
Twenty years of the FIFA Medical Assessment and Research Centre: from ‘Medicine for Football’ to ‘Football for Health’
Authors: Jiri Dvorak, Astrid Junge
Journal: British Journal of Sports Medicine (2015)

FIFA), asked: "What can medicine and science do to improve the game of football?"Although a simple question, it led to the founding of the FIFA Medical Assessment and Research Centre (F-MARC) during the 1994 FIFA World Cup USA.The objective of F-MARC was to reduce football injuries at all levels of play, and to promote football as a health enhancing leisure activity improving social behaviour.
Effects of duration and severity of arterial hypertension and cardiac hypertrophy on coronary vasodilator reserve.
Authors: R D Wangler, K G Peters, M L Marcus, R J Tomanek
Journal: Circulation Research (1982)

Cardiac hypertrophy is associated with a decrease in coronary reserve. However, factors which may modulate the interaction between myocardial growth and vascular proliferation, such as duration and severity of hypertrophy, have not been evaluated. We measured myocardial perfusion with microspheres in conscious, chronically instrumented. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats at 3, 7, and 15 months of age; and in SHR stroke-prone (SHR-SP) rats at 13-14 months of age. Myocardial perfusion was measured with microspheres in awake rats at rest and during maximal coronary dilation produced by dipyridamole infusion (2.0 mg/kg per min, iv). Arterial pressure was significantly elevated (P less than or equal to 0.05) in all hypertensive groups (vs. age-matched WKY), both at rest and during dipyridamole infusion. Left ventricular mass in the SHR rats was increased significantly (P less than or equal to 0.05) by 14%, 28%, and 29% at 3, 7, and 15 months, respectively. Left ventricular mass in the SHR-SP group was increased by 50% (P less than or equal to 0.05) compared to the 15-month-old WKY. Left ventricular minimal coronary vascular resistance (per gram) was significantly greater (P less than or equal to 0.05) in SHR at 7 months, and in the SHR-SP group (66% and 60%, respectively). Right ventricular minimal coronary vascular resistance was significantly greater (P less than or equal to 0.05) in SHR at 7 and 15 months (50%), and in the SHR-SP group (122%), compared to 15-month-old WKY. The results indicate the following: (1) the increase in minimal coronary vascular resistance between SHR and WKY rats was greatest when left ventricular hypertrophy peaked (7 months) and was no longer present after left ventricular hypertrophy had stabilized. (2) In 14-month-old SHR-SP rats, with more severe left ventricular hypertrophy and hypertension, minimal coronary vascular resistance was considerably higher than in SHR of approximately the same age. (3) Long-term arterial hypertension was associated with a higher right ventricular minimal coronary vascular resistance. Resistance appeared to change in proportion to the severity of hypertension, and the changes were independent of the presence of right ventricular hypertrophy.
Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate.
Authors: F Gaspari, N Perico, P Ruggenenti, L Mosconi, C S Amuchastegui, E Guerini, E Daina, G Remuzzi
Journal: Journal of the American Society of Nephrology (1995)

Renal clearance of inulin is the best available indicator of GFR but cannot be used routinely for clinical purposes and is also difficult to perform for clinical investigation when repeated measurements are required. The aim of this study was to find a reliable alternative to inulin clearance that would allow one to avoid the use of radioactivity and problems related to the continuous infusion of the marker. The plasma clearance of unlabeled iohexol, a nonionic contrast agent, was used. Forty-one patients (creatinine clearance 6 to 160 mL/min per 1.73 m2) underwent simultaneous measurements of renal clearance of inulin and plasma clearance of iohexol. Iohexol was given as a single iv dose, and blood samples were drawn up to 600 min after the administration. Iohexol concentrations (by HPLC) were analyzed by a two-compartment, open-model system. A highly significant correlation between the plasma clearance of iohexol and the renal clearance of inulin over a wide range of GFR values was found. By analyzing the data with a simplified method that uses a one-compartment model corrected with the Bröchner-Mortensen formula, an excellent correlation with the inulin clearance was also observed. When only patients with moderate to severe renal failure were considered, a significant correlation between the two methods was found. A further comparison between GFR determined with iohexol and iopromide, a new low-osmolarity, low-viscosity contrast medium, was also performed in a subgroup of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Photodynamic Therapy Causes Cross-linking of Signal Transducer and Activator of Transcription Proteins and Attenuation of Interleukin-6 Cytokine Responsiveness in Epithelial Cells
Authors: Weiguo Liu, Allan R. Oseroff, Heinz Baumann
Journal: Cancer Research (2004)

Abstract Photodynamic therapy (PDT) is a local treatment of cancers. The principle of PDT is the production of reactive oxygen species, in particular singlet oxygen, by light activation of a photosensitizer introduced into the target cells. The direct photochemical and subsequent redox reactions can lead to cell death. This study sought to identify effects occurring during PDT and some of their consequences in surviving cells. Using epithelial cells in tissue culture and in tumors, several distinct PDT-mediated reactions were found, including global dephosphorylation of proteins, induced phosphorylation of a 71-kDa protein, initiation of cellular stress responses, structural modification and loss of epidermal growth factor receptor, and cross-linking of proteins. Specific covalent cross-linking of nonactivated signal transducer and activator of transcription (STAT)-3, and to a lesser extent of STAT1 and STAT4, correlated with PDT dose. Cross-linked STAT3 was primarily localized to the cytoplasm and failed to bind to DNA. The combination of STAT cross-linking and inactivation of receptor functions rendered PDT-treated cells refractory for at least 24 hours to interleukin-6 and oncostatin M, cytokines known to be elevated at site of tissue damage and inflammation. It is suggested that the loss of responsiveness to these inflammatory cytokines in the PDT-treated field assists tumor cells in evading the growth-suppressive activity of these mediators expected to be present at tissue sites after PDT.
Open-Label, Uncontrolled, Multicenter Phase II Study to Evaluate the Efficacy and Toxicity of Cetuximab As a Single Agent in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Failed to Respond to Platinum-Based Therapy
Authors: Jan B. Vermorken, José Trigo, Ricardo Hitt, Piotr Koralewski, Eduardo Diaz-Rubio, Frédéric Rolland, Rainald Knecht, Nadia Amellal, Armin Schueler, José Baselga
Journal: Journal of Clinical Oncology (2007)

Purpose To evaluate the efficacy and safety of the epidermal growth factor receptor–directed monoclonal antibody cetuximab administered as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who experience disease progression on platinum therapy. Patients and Methods An open-label multicenter study in which patients with disease progression on two to six cycles of platinum therapy received single-agent cetuximab (initial dose 400 mg/m 2 followed by subsequent weekly doses of 250 mg/m 2 ) for ≥ 6 weeks (single-agent phase). Patients who experienced disease progression could receive salvage therapy with cetuximab plus platinum (combination-therapy phase). From June 2001 to December 2002, 103 patients were enrolled and treated with cetuximab, 53 of whom subsequently received combination therapy. Results In the single-agent phase, response rate was 13%, disease control rate (complete response/partial response/stable disease) was 46%, and median time to progression (TTP) was 70 days. During the combination-therapy phase, the objective response rate was zero, disease control rate was 26%, and TTP was 50 days. Median overall survival was 178 days. Treatment was well tolerated. The most common cetuximab-related adverse events in the single-agent phase were skin reactions, particularly rash (49% of patients, mainly grade 1 or 2). There was one treatment-related death due to an infusion-related reaction. Conclusion Single-agent cetuximab was active and generally well tolerated in the treatment of recurrent and/or metastatic SCCHN that progressed on platinum therapy. Response was comparable to that seen with cetuximab plus platinum combination regimens in the same setting.
Awareness of environmental risks and protective actions among minority women in Northern Manhattan.
Authors: David Thompson Evans, Mindy Thompson Fullilove, Lesley Green, Moshe Levison
Journal: Environmental Health Perspectives (2002)

We report findings of a survey of 555 women 18-35 years of age living in Northern Manhattan in New York City. The survey was conducted by the Columbia Center for Children's Environmental Health (CCCEH) to learn what community women knew about environmental risks to health and what they did to protect themselves and their families, to validate the findings of focus groups held with community women, and to provide information for planning the Healthy Home, Healthy Child campaign sponsored by CCCEH. Survey findings showed that overall awareness of environmental risks to children's health was high, with more than 95% of respondents identifying lead, household pests, pesticides, environmental tobacco smoke, and drugs as harmful to health. Similarly, more than 95% of respondents reported taking one or more protective actions to reduce these risks, suggesting that these factors significantly concern women living in Northern Manhattan. The reported levels of specific protective actions to reduce these risks, however, varied greatly. In each area of risk the most frequently reported actions were effective ones, but many other important protective actions were rarely mentioned, suggesting that there was room for an educational campaign to teach women new ways to protect their families. Survey respondents and CCCEH scientists differed in the priorities they placed on the importance of key protective actions, confirming earlier focus group findings and suggesting the importance of incorporating community concerns into the planning of environmental campaigns.
Quantification and time course of microvascular obstruction by contrast-enhanced echocardiography and magnetic resonance imaging following acute myocardial infarction and reperfusion
Authors: Katherine C Wu, Raymond J Kim, David A Bluemke, Carlos E Rochitte, Elias A Zerhouni, Lewis C Becker, Joao A.C Lima
Journal: Journal of the American College of Cardiology (1998)

Objectives. We aimed to validate contrast-enhanced echocardiography (CE) in the quantification of microvascular obstruction (MO) against magnetic resonance imaging (MRI) and the histopathologic standards of radioactive microspheres and thioflavin-S staining. We also determined the time course of MO at days 2 and 9 after infarction and reperfusion. Background. Postinfarction MO occurs because prolonged ischemia produces microvessel occlusion at the infarct core, preventing adequate reperfusion. Microvascular obstruction expands up to 48 h after reperfusion; the time course beyond 2 days is unknown. Though used to study MO, CE has not been compared with MRI and thioflavin-S, which yield precise visual maps of MO. Methods. Ten closed-chest dogs underwent 90-min coronary artery occlusion and reperfusion. Both CE and MRI were performed at 2 and 9 days after reperfusion. The MO regions by both methods were quantified as percent left ventricular (% LV) mass. Radioactive microspheres were injected for blood flow determination. Postmortem, the myocardium was stained with thioflavin-S and 2,3,5-triphenyltetrazolium chloride. Results. Expressed as % total LV, MO by MRI matched in size MO by microspheres using a flow threshold of <40% remote (4.96 ± 3.52% vs. 5.32 ± 3.98%, p = NS). For matched LV cross sections, MO by CE matched in size MO by microspheres using a flow threshold of <60% remote (13.27 ± 4.31% vs. 13.5 ± 4.94%, p = NS). Both noninvasive techniques correlated well with microspheres (MRI vs. CE, r = 0.87 vs. 0.74; p = NS). Microvascular obstruction by CE corresponded spatially to MRI-hypoenhanced regions and thioflavin-negative regions. For matched LV slices at 9 days after reperfusion, MO measured 12.94 ± 4.51% by CE, 7.11 ± 3.68% by MRI and 9.18 ± 4.32% by thioflavin-S. Compared to thioflavin-S, both noninvasive techniques correlated well (CE vs. MRI, r = 0.79 vs. 0.91; p = NS). Microvascular obstruction size was unchanged at 2 and 9 days (CE: 13.23 ± 4.11% vs. 12.69 ± 4.97%; MRI: 5.53 ± 4.94% vs. 4.68 ± 3.44%; p = NS for both). Conclusions. Both CE and MRI can quantify MO. Both correlate well with the histopathologic standards. While MRI can detect regions of MO with blood flow <40% of remote, the threshold for MO by CE is <60% remote. The extent of MO is unchanged at 2 and 9 days after reperfusion.
Lipocytes from normal rat liver release a neutral metalloproteinase that degrades basement membrane (type IV) collagen.
Authors: M J Arthur, S L Friedman, F J Roll, D M Bissell
Journal: Journal of Clinical Investigation (1989)

We report a proteinase that degrades basement-membrane (type IV) collagen and is produced by the liver. Its cellular source is lipocytes (fat-storing or Ito cells). Lipocytes were isolated from normal rat liver and established in primary culture. The cells synthesize and secrete a neutral proteinase, which by gelatin-substrate gel electrophoresis and gel filtration chromatography, has a molecular mass of 65,000 D. The enzyme is secreted in latent form and is activated by p-aminophenylmercuric acetate but not by trypsin. Enzyme activity in the presence of EDTA is restored selectively by zinc and is unaffected by serine-protease inhibitors. In assays with radiolabeled soluble substrates, it degrades native type IV (basement membrane) collagen but not interstitial collagen types I or V and exhibits no activity against laminin or casein. At temperatures causing partial denaturation of soluble collagen in vitro, it rapidly degrades types I and V. Thus, it is both a type IV collagenase and gelatinase. The enzyme may play a role in initiating breakdown of the subendothelial matrix in the Disse space as well as augmenting the effects of collagenases that attack native interstitial collagen.
Current Pharmacologic Treatment of Dementia: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians
Authors: Amir Qaseem, Vincenza Snow, J. Thomas Cross, Mary Ann Forciea, Robert Hopkins, Paul Shekelle, Alan Adelman, David Mehr, Kenneth Schellhase, Doug Campos-Outcalt, Pasqualina Santaguida, Douglas K. Owens, Donald E. Casey, Paul Dallas, Nancy C. Dolan, Lakshmi Halasyamani, Robert H. Hopkins, Eric M. Wall, Jonathan E. Rodnick, Kenneth G. Schellhase, Steven W. Strode, Kurtis S. Elward, James W. Mold, Jonathan L. Temte, Frederick M. Chen, Thomas F. Koinis, Donya A. Powers, James M. Gill, Kevin Peterson, Robert C. Marshall, Herbert F. Young, Bellinda K. Schoof
Journal: Annals of Internal Medicine (2008)

Description: The American College of Physicians and American Academy of Family Physicians developed this guideline to present the available evidence on current pharmacologic treatment of dementia. Methods: The targeted literature search included evidence related to the effectiveness of 5 U.S. Food and Drug Administration–approved pharmacologic therapies for dementia for outcomes in the domains of cognition, global function, behavior/mood, and quality of life/activities of daily living. Recommendation 1: Clinicians should base the decision to initiate a trial of therapy with a cholinesterase inhibitor or memantine on individualized assessment. (Grade: weak recommendation, moderate-quality evidence.) Recommendation 2: Clinicians should base the choice of pharmacologic agents on tolerability, adverse effect profile, ease of use, and cost of medication. The evidence is insufficient to compare the effectiveness of different pharmacologic agents for the treatment of dementia. (Grade: weak recommendation, low-quality evidence.) Recommendation 3: There is an urgent need for further research on the clinical effectiveness of pharmacologic management of dementia.
Monoclonal Antibodies to Fibroblast Growth Factor Receptor 2 Effectively Inhibit Growth of Gastric Tumor Xenografts
Authors: Wei-meng Zhao, Lihong Wang, Hangil Park, Sophea Chhim, Melanie Tanphanich, Masakazu Yashiro, K. Jin Kim
Journal: Clinical Cancer Research (2010)

Overexpression of fibroblast growth factor receptor 2 (FGFR2) may be a causative factor of a number of human tumors, especially gastric tumors of the poorly differentiated type. We investigated whether monoclonal antibodies (mAbs) directed against FGFR2 can inhibit the growth of tumors in xenograft models.We generated and characterized 3 mAbs that recognize different epitopes on FGFR2: GAL-FR21, GAL-FR22, and GAL-FR23. The ability of the mAbs to recognize the FGFR2IIIb and FGFR2IIIc isoforms of FGFR2 was determined, as was their ability to block binding of FGF ligands to FGFR2. The capability of the mAbs to inhibit FGF-induced FGFR2 phosphorylation and to downmodulate FGFR2 expression was also investigated. Finally, the ability of the anti-FGFR2 mAbs to inhibit tumor growth was determined by establishing xenografts of SNU-16 and OCUM-2M human gastric tumor cell lines in nude mice, treating with each mAb (0.5-5 mg/kg intraperitoneally twice weekly) and monitoring tumor size.Of the 3 mAbs, GAL-FR21 binds only the FGFR2IIIb isoform, whereas GAL-FR22 and GAL-FR23 bind to both the FGFR2IIIb and FGFR2IIIc forms, with binding regions respectively in the D3, D2-D3, and D1 domains of FGFR2. GAL-FR21 and GAL-FR22 blocked the binding of FGF2, FGF7 and FGF10 to FGFR2IIIb. GAL-FR21 inhibited FGF2 and FGF7 induced phosphorylation of FGFR2, and both mAbs downmodulated FGFR2 expression on SNU-16 cells. These mAbs effectively inhibited growth of established SNU-16 and OCUM-2M xenografts in mice.Anti-FGFR2 mAbs GAL-FR21 and GAL-FR22 have potential for the treatment of gastric and other tumors.
Coronary Risk Factors in the Young
Authors: E A Stein, C J Glueck, J A Morrison
Journal: Annual Review of Medicine (1981)

The exceptional growth in risk factor assessment and the efficacy of primary prevention in childhood of atherosclerotic and hypertensive diseases is the subject of entire books that have recently collated the results of multiple investigators (58, 59). It is a topic well beyond the constraints of this review. It appears that the major "adult" CHD risk factors, including elevated total plasma and low-density lipoprotein cholesterol, elevated triglyceride, reduced high-density lipoprotein cholesterol, high blood pressure, obesity, and initiation of cigarette smoking can usually be recognized in children. There are, as yet, no longitudinal studies that control for one or more of these CHD risk factor variables to determine whether future development of CHD could be prevented or ameliorated. In the absence of unequivocal longitudinal studies of efficacy of intervention, prudent, safe, and well-supervised interventions should be carried out only after exhaustive proof of diagnosis (58). The recently summarized data suggest that they hyperlipoproteinemias, high blood pressure, obesity, and initiation of cigarette smoking can (with varying degrees of success) be dealt with during childhood and adolescence.
AN EXPERIMENTAL TEST OF NUZUM'S ANTIPOLIOMYELITIC SERUM
Authors: Harold L. Amoss, Frederick Eberson
Journal: The Journal of Experimental Medicine (1918)

The antistreptococcic serum of Nuzum and Willy has failed to show in the monkey neutralizing or therapeutic power when applied by their methods against small doses of the virus of poliomyelitis. Under the same conditions the serum of monkeys recovered from experimental poliomyelitis proved neutralizing and protective. The experimental and other evidence adduced by those who regard the streptococcus as playing an essential part in the pathology of epidemic poliomyelitis and the antistreptococcic sera as exhibiting therapeutic properties for man and monkeys is regarded as imperfect and inconclusive.
Can telemedicine improve CPAP adherence?
Authors: M. Kwiatkowska, N. Ayas
Journal: Thorax (2010)

Obstructive sleep apnoea (OSA) is a common, important disease associated with daytime sleepiness and a reduced quality of life.Moreover, untreated OSA is associated with increased healthcare utilisation and a significantly increased risk of motor vehicle crashes, hypertension, coronary artery disease and stroke. 1 Treatment of patients with continuous positive airway pressure (CPAP) improves quality of life and daytime sleepiness.CPAP treatment may also substantially reduce rates of cardiac events and motor vehicle crashes. 2 3One of the major barriers to CPAP treatment is adherence.Many patients reject, discontinue or use it irregularly or suboptimally.The rate of CPAP discontinuation in the first 3 years of prescription ranges from 12% to 25%. 4 When patients do not use CPAP sufficiently, clinical outcomes are compromised, 5 demonstrating that optimising adherence is an important aspect of patient management.