tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of Screening for HIV in the Era of Highly Active Antiretroviral Therapy
Authors: Gillian D. Sanders, Ahmed M. Bayoumi, Vandana Sundaram, S. Pinar Bilir, Christopher P. Neukermans, Chara E. Rydzak, Lena R. Douglass, Laura C. Lazzeroni, Mark Holodniy, Douglas K. Owens
Journal: New England Journal of Medicine (2005)

The costs, benefits, and cost-effectiveness of screening for human immunodeficiency virus (HIV) in health care settings during the era of highly active antiretroviral therapy (HAART) have not been determined.We developed a Markov model of costs, quality of life, and survival associated with an HIV-screening program as compared with current practice. In both strategies, symptomatic patients were identified through symptom-based case finding. Identified patients started treatment when their CD4 count dropped to 350 cells per cubic millimeter. Disease progression was defined on the basis of CD4 levels and viral load. The likelihood of sexual transmission was based on viral load, knowledge of HIV status, and efficacy of counseling.Given a 1 percent prevalence of unidentified HIV infection, screening increased life expectancy by 5.48 days, or 4.70 quality-adjusted days, at an estimated cost of 194 dollars per screened patient, for a cost-effectiveness ratio of 15,078 dollars per quality-adjusted life-year. Screening cost less than 50,000 dollars per quality-adjusted life-year if the prevalence of unidentified HIV infection exceeded 0.05 percent. Excluding HIV transmission, the cost-effectiveness of screening was 41,736 dollars per quality-adjusted life-year. Screening every five years, as compared with a one-time screening program, cost 57,138 dollars per quality-adjusted life-year, but was more attractive in settings with a high incidence of infection. Our results were sensitive to the efficacy of behavior modification, the benefit of early identification and therapy, and the prevalence and incidence of HIV infection.The cost-effectiveness of routine HIV screening in health care settings, even in relatively low-prevalence populations, is similar to that of commonly accepted interventions, and such programs should be expanded.
Mitral valve replacement: Long-term results, with particular reference to changes in pulmonary vascular resistance
Authors: J. Hamer, T. Boulton, J. Fleming, G. W. Hayward, I. M. Hill, I. Monro, G. Simon, C. S. Tubbs
Journal: Thorax (1968)

The first 16 patients to have mitral valve replacement with the Starr-Edwards prosthesis at St. Bartholomew9s Hospital, London, were reviewed from one to three years after operation. These patients had presented with serious mitral valve disease and there was a high incidence of severe dyspnoea and persistent congestive failure before operation. There were four operative deaths, and two survivors had poor results due to regurgitation alongside the prosthesis. The remaining 10 patients showed considerable improvement. Although no diuretics were given after operation there was little dyspnoea and congestive failure resolved. Anticoagulant therapy is given after operation, and there have been few embolic incidents. The pulmonary vascular resistance was raised to between 6 and 11 units before operation in six patients. There was no undue mortality in this group, and post-operative cardiac catheterization showed a considerable fall in resistance and an increase in cardiac output, suggesting resolution of the pulmonary vascular obstruction. Tricuspid incompetence in these patients disappeared post-operatively. We conclude that mitral valve replacement can restore a patient severely disabled by mitral valve disease to a nearly normal life. We do not regard pulmonary hypertension as a contraindication to operation.
Development and validation of a questionnaire to measure the severity of functional limitations and reduction of sports ability in German-speaking patients with exercise-induced leg pain
Authors: Tanja Nauck, Heinz Lohrer, Nat Padhiar, John B King
Journal: British Journal of Sports Medicine (2012)

Background Currently, there is no generally agreed measure available to quantify a subject's perceived severity of exercise-induced leg pain symptoms. The aim of this study was to develop and validate a questionnaire that measures the severity of symptoms that impact on function and sports ability in patients with exercise-induced leg pain. Methods The exercise-induced leg pain questionnaire for German-speaking patients (EILP-G) was developed in five steps: (1) initial item generation, (2) item reduction, (3) pretesting, (4) expert meeting and (5) validation. The resulting EILP-G was tested for reliability, validity and internal consistency in 20 patients with exercise-induced leg pain, 20 asymptomatic track and field athletes serving as a population at risk and 33 asymptomatic sport students. Results The patient group scored the EILP-G questionnaire significantly lower than both control groups (each p&lt;0.001). Test–retest demonstrates an excellent reliability in all tested groups (Intraclass Correlation Coefficient, ICC=0.861–0.987). Concurrent validity of the EILP-G questionnaire showed a substantial agreement when correlated with the chronic exertional compartment syndrome classification system of Schepsis (r=−0.743; p&lt;0.001). Internal consistency for the EILP-G questionnaire was 0.924. Conclusions EILP-G questionnaire is a valid and reliable self-administered and disease-related outcome tool to measure the severity of symptoms that impact on function and sports ability in patients with exercise-induced leg pain. It can be recommended as a robust tool for measuring the subjectively perceived severity in German-speaking patients with exercise-induced leg pain.
Angiopoietin-4 Promotes Glioblastoma Progression by Enhancing Tumor Cell Viability and Angiogenesis
Authors: Melissa K. Brunckhorst, Hui Wang, Rong Lu, Qin Yu
Journal: Cancer Research (2010)

Glioblastoma multiforme (GBM) is a highly invasive and vascularized aggressive brain tumor. Less than 10% of GBM patients survive >5 years after diagnosis. Angiogenesis plays an important role in GBM growth, and antiangiogenesis-based therapies have shown clinical efficacy for GBM patients. Unfortunately, therapeutic resistance often develops in these patients, suggesting that GBM cells are capable of switching their dependency on one proangiogenic signaling pathway to an alternative one. Therefore, it is important to identify novel angiogenic factors that play essential roles in tumor angiogenesis and GBM progression. Angiopoietins (Ang-1, Ang-2, and Ang-4) are the ligands of the Tie-2 receptor tyrosine kinase (RTK). The roles of Ang-1 and Ang-2 in tumor angiogenesis have been established. However, little is known about how Ang-4 affects tumor angiogenesis and GBM progression and the mechanism underlying its effects. In our current study, we establish that Ang-4 is upregulated in human GBM tissues and cells. We show that, like endothelial cells, human GBM cells express Tie-2 RTK. We first establish that Ang-4 promotes in vivo growth of human GBM cells by promoting tumor angiogenesis and directly activating extracellular signal-regulated kinase 1/2 (Erk1/2) in GBM cells. Our results establish the novel effects of Ang-4 on tumor angiogenesis and GBM progression and suggest that this pro-GBM effect of Ang-4 is mediated by promoting tumor angiogenesis and activating Erk1/2 kinase in GBM cells. Together, our results suggest that the Ang-4-Tie-2 functional axis is an attractive therapeutic target for GBM.
Inhibition of mTOR Signaling With Rapamycin Regresses Established Cardiac Hypertrophy Induced by Pressure Overload
Authors: Julie R. McMullen, Megan C. Sherwood, Oleg Tarnavski, Li Zhang, Adam L. Dorfman, Tetsuo Shioi, Seigo Izumo
Journal: Circulation (2004)

Rapamycin is a specific inhibitor of the mammalian target of rapamycin (mTOR). We recently reported that administration of rapamycin before exposure to ascending aortic constriction significantly attenuated the load-induced increase in heart weight by approximately 70%.To examine whether rapamycin can regress established cardiac hypertrophy, mice were subjected to pressure overload (ascending aortic constriction) for 1 week, echocardiography was performed to verify an increase in ventricular wall thickness, and mice were given rapamycin (2 mg x kg(-1) x d(-1)) for 1 week. After 1 week of pressure overload (before treatment), 2 distinct groups of animals became apparent: (1) mice with compensated cardiac hypertrophy (normal function) and (2) mice with decompensated hypertrophy (dilated with depressed function). Rapamycin regressed the pressure overload-induced increase in heart weight/body weight (HW/BW) ratio by 68% in mice with compensated hypertrophy and 41% in mice with decompensated hypertrophy. Rapamycin improved left ventricular end-systolic dimensions, fractional shortening, and ejection fraction in mice with decompensated cardiac hypertrophy. Rapamycin also altered the expression of some fetal genes, reversing, in part, changes in alpha-myosin heavy chain and sarcoplasmic reticulum Ca2+ ATPase.Rapamycin may be a therapeutic tool to regress established cardiac hypertrophy and improve cardiac function.
Acute effects of flutter breathing exercises on exhaled nitric oxide and airway resistance
Authors: A.C. Gastaldi, O. Usmani, P.J. Barnes, P. Paredi
Journal: European Respiratory Journal (2013)

The flutter valve is a physiotherapy device that produces oscillations and positive expiratory pressure that may help clear respiratory secretions. Its effects on airway resistance and inflammation are unknown.  Objective: To evaluate the acute effects of breathing exercises with a flutter device on exhaled nitric oxide (FeNO), a marker of inflammation, and airway resistance as assessed by impulse oscillometry (IOS) in healthy subjects.  Methods: 14 healthy subjects, mean age 39±9 years were enrolled in the study. Whole breath respiratory resistance at 5Hz (R5) and reactance (X5) were measured by impulse oscillometry (IOS, Jaeger, Wurzburg, Germany) and FeNO at the exhalation flow rate of 50 ml/s by chemiluminescence (Niox Flex, Aerocrine, Sweden). The measurements were performed at baseline, immediately following 30 minutes of flutter breathing (Varioraw SARL, Scandipharm Inc, Alabama, USA) and repeated using a control flutter-sham device that does not produce vibrations.  Results: FeNO levels were significantly decreased after flutter breathing (26.2±21.9 and 23.5±20.6 ppb; p  Conclusion: The use of a flutter device significantly decreases FeNO levels without affecting airway resistance. This may be due to improvement of the ventilation/perfusion, diffusion and clearance of NO. Further studies are required to investigate flutter breathing in patients with airway disease.  Granted by FAPESP/Brazil.
Children's charity criticises global immunisation initiative
Authors: F. Fleck
Journal: BMJ (2002)

A global initiative that seeks to save millions of children's lives by immunisation is in danger of saddling the world's poorest countries with expensive vaccine regimes they cannot afford and perhaps do not need, a new study has found.

The study, conducted by the UK charity Save the Children and the London School of Hygiene and Tropical Medicine, criticised the Global Alliance for Vaccines and Immunisations (GAVI) for including managers from pharmaceutical companies on its governing board, saying that this created a potential conflict of interest.

“GAVI needs to ensure that it can …
Patient assessment of treatment satisfaction: methods and practical issues
Authors: D A Revicki
Journal: Gut (2004)

Measurement of treatment satisfaction in gastro-oesophageal reflux disease (GORD) is compromised by an insufficient conceptual foundation and poor assessment methods. The current state of the art in measuring treatment satisfaction is incomplete, and the existing measurement is insufficient. Here, the definition, conceptualisation, application, and methodological issues associated with measurement of treatment satisfaction in GORD are reviewed. Treatment satisfaction may be important for differentiating among GORD treatments, and for monitoring patient outcomes in clinical practice.
IMMUNOCHEMICAL STUDIES OF TWENTY MOUSE MYELOMA PROTEINS: EVIDENCE FOR TWO GROUPS OF PROTEINS SIMILAR TO GAMMA AND BETA-2A GLOBULINS IN MAN
Authors: John L. Fahey
Journal: The Journal of Experimental Medicine (1961)

The serum myeloma proteins associated with 20 mouse plasma cell tumors in C(3)H or BALB/c mice that had proved transplantable were characterized by electrophoretic and immunochemical techniques. Although the myeloma proteins ranged in electrophoretic mobility from gamma to alpha globulins, they could be divided into two groups, the gamma type and the beta type myeloma globulins, on the basis of characteristic immunochemical properties. Gamma type myeloma proteins (5563, MPC-11) showed a close immunochemical relationship to normal mouse gamma globulins. Eighteen beta type mouse myeloma proteins migrated as beta or alpha globulins on zone electrophoresis. These proteins shared common antigenic features which permitted their recognition, separate from gamma myeloma proteins. The beta type myeloma proteins were shown to be related to a beta globulin component present in normal serum. Strain differences were observed for the normal beta globulin component believed to be formed in plasma cells. The proteins formed in mouse plasma cells were found to be antigenically complex. Shared antigenic determinants as well as distinctive antigenic determinants were detected when representative myeloma proteins were purified and compared by the Ouchterlony double diffusion technique. The myeloma proteins associated with each of the transplantable plasma cell tumors in mice are regarded as distinctive and characteristic products of plasma cell metabolism. The variety of myeloma globulins was similar for plasma cell tumors arising in C(3)H as well as in BALB/c mice, indicating that differences in mouse strains would not account for the differences among the myeloma globulins. These differences, however, may be due to differences among the normal plasma cells from which the malignant cells are derived. If this is so, the variety of myeloma globulins reflect the variety of plasma cells present normally.
The phosphatase CD148 promotes airway hyperresponsiveness through SRC family kinases
Authors: Tamiko R. Katsumoto, Makoto Kudo, Chun Chen, Aparna Sundaram, Elliott C. Callahan, Jing W. Zhu, Joseph Lin, Connor E. Rosen, Boryana N. Manz, Jae W. Lee, Michael A. Matthay, Xiaozhu Huang, Dean Sheppard, Arthur Weiss
Journal: Journal of Clinical Investigation (2013)

Increased airway smooth muscle (ASM) contractility and the development of airway hyperresponsiveness (AHR) are cardinal features of asthma, but the signaling pathways that promote these changes are poorly understood. Tyrosine phosphorylation is tightly regulated by the opposing actions of protein tyrosine kinases and phosphatases, but little is known about whether tyrosine phosphatases influence AHR. Here, we demonstrate that genetic inactivation of receptor-like protein tyrosine phosphatase J (Ptprj), which encodes CD148, protected mice from the development of increased AHR in two different asthma models. Surprisingly, CD148 deficiency minimally affected the inflammatory response to allergen, but significantly altered baseline pulmonary resistance. Mice specifically lacking CD148 in smooth muscle had decreased AHR, and the frequency of calcium oscillations in CD148-deficient ASM was substantially attenuated, suggesting that signaling pathway alterations may underlie ASM contractility. Biochemical analysis of CD148-deficient ASM revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SRC family kinases (SFKs), implicating CD148 as a critical positive regulator of SFK signaling in ASM. The effect of CD148 deficiency on ASM contractility could be mimicked by treatment of both mouse trachea and human bronchi with specific SFK inhibitors. Our studies identify CD148 and the SFKs it regulates in ASM as potential targets for the treatment of AHR.
Optimized mapping of slow pathway ablation guided by subthreshold stimulation: a randomized prospective study in patients with recurrent atrioventricular nodal re-entrant tachycardia
Authors: Stephan Willems, Christian Weiss, Mohammad Shenasa, Rodolfo Ventura, Matthias Hoffmann, Thomas Meinertz
Journal: Journal of the American College of Cardiology (2001)
A model combining clinical assessment and NT-proBNP level accurately predicted heart failure in ED patients with dyspnea
Authors: James Brophy
Journal: Annals of Internal Medicine (2010)

ACP Journal Club19 January 2010A model combining clinical assessment and NT-proBNP level accurately predicted heart failure in ED patients with dyspneaJames Brophy, MD, PhDJames Brophy, MD, PhDMcGill University, Montreal, Quebec, Canada (J.B.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-2-201001190-02013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSteinhart B, Thorpe KE, Bayoumi AM, et al. Improving the diagnosis of acute heart failure using a validated prediction model. J Am Coll Cardiol. 2009;54:1515-21. https://pubmed.ncbi.nlm.nih.gov/19815122Clinical Impact RatingsEmergency Med: Hospitalists: Cardiology: Author, Article, and Disclosure InformationAffiliations: McGill University, Montreal, Quebec, Canada (J.B.)This article was published at Annals.org on 5 January 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAcute Heart Failure Syndromes: Emergency Department Presentation, Treatment, and Disposition: Current Approaches and Future Aims 19 January 2010Volume 152, Issue 2Page: JC1-13KeywordsCohort studiesDyspneaHeart failureHospitalistsMathematical modelsNatriuretic peptidesRenal failure ePublished: 19 January 2010 Issue Published: 19 January 2010 CopyrightCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
18Fluorodeoxyglucose Positron Emission Tomography in the Diagnosis and Staging of Lung Cancer: A Systematic Review
Authors: Y. C. Ung, D. E. Maziak, J. A. Vanderveen, C. A. Smith, K. Gulenchyn, C. Lacchetti, W. K. Evans
Journal: JNCI Journal of the National Cancer Institute (2007)

Lung cancer is the leading cause of cancer-related death in industrialized countries. The overall mortality rate for lung cancer is high, and early diagnosis provides the best chance for survival. Diagnostic tests guide lung cancer management decisions, and clinicians increasingly use diagnostic imaging in an effort to improve the management of patients with lung cancer. This systematic review, an expansion of a health technology assessment conducted in 2001 by the Institute for Clinical and Evaluative Sciences, evaluates the accuracy and utility of 18 fluorodeoxyglucose positron emission tomography (PET) in the diagnosis and staging of lung cancer. Through a systematic search of the literature, we identified relevant health technology assessments, randomized trials, and meta-analyses published since the earlier review, including 12 evidence summary reports and 15 prospective studies of the diagnostic accuracy of PET. PET appears to have high sensitivity and reasonable specificity for differentiating benign from malignant lesions as small as 1 cm. PET appears superior to computed tomography imaging for mediastinal staging in non–small cell lung cancer (NSCLC). Randomized trials evaluating the utility of PET in potentially resectable NSCLC report conflicting results in terms of the relative reduction in the number of noncurative thoracotomies. PET has not been studied as extensively in patients with small-cell lung cancer, but the available data show that it has good accuracy in staging extensive- versus limited-stage disease. Although the current evidence is conflicting, PET may improve results of early-stage lung cancer by identifying patients who have evidence of metastatic disease that is beyond the scope of surgical resection and that is not evident by standard preoperative staging procedures. Further trials are necessary to establish the clinical utility of PET as part of the standard preoperative assessment of early-stage lung cancer.
Genetic control of sodium channel function
Authors: H Tan
Journal: Cardiovascular Research (2003)

Sodium ion (Na) influx through cardiac Na channels triggers the action potential in cells of the working myocardium and the specialized conduction system. Na channels thus act as key molecular determinants of cardiac excitability and impulse propagation. Na channel dysfunction may cause life-threatening arrhythmias. Here, we review the ways in which Na channel function can be aberrant due to genetic changes. We discuss how biophysical studies of mutant Na channels combined with precise clinical phenotyping may improve our understanding of Na channel function in health and disease and may be useful as a model from which to derive improved treatment strategies for common disease.
GNOSIS: Guidelines for neuro-oncology: Standards for investigational studies—reporting of phase 1 and phase 2 clinical trials
Authors: Susan M Chang, Sharon L Reynolds, Nicholas Butowski, Kathleen R Lamborn, Jan C Buckner, Richard S Kaplan, Darell D Bigner
Journal: Neuro-Oncology (2005)

We present guidelines to standardize the reporting of phase 1 and phase 2 neuro-oncology trials. The guidelines are also intended to assist with accurate interpretation of results from these trials, to facilitate the peer-review process, and to expedite the publication of important and accurate manuscripts. Our guidelines are summarized in a checklist format that can be used as a framework from which to construct a phase 1 or 2 clinical trial.
Effect of Paricalcitol on Left Ventricular Mass and Function in CKD—The OPERA Trial
Authors: Angela Yee-Moon Wang, Fang Fang, John Chan, Yue-Yi Wen, Shang Qing, Iris Hiu-Shuen Chan, Gladys Lo, Kar-Neng Lai, Wai-Kei Lo, Christopher Wai-Kei Lam, Cheuk-Man Yu
Journal: Journal of the American Society of Nephrology (2013)

Vitamin D seems to protect against cardiovascular disease, but the reported effects of vitamin D on patient outcomes in CKD are controversial. We conducted a prospective, double blind, randomized, placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular (LV) mass in patients with stages 3-5 CKD with LV hypertrophy. Subjects with echocardiographic criteria of LV hypertrophy were randomly assigned to receive either oral paricalcitol (1 μg) one time daily (n=30) or matching placebo (n=30) for 52 weeks. The primary end point was change in LV mass index over 52 weeks, which was measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volume, echocardiographic measures of systolic and diastolic function, biochemical parameters of mineral bone disease, and measures of renal function. Change in LV mass index did not differ significantly between groups (median [interquartile range], -2.59 [-6.13 to 0.32] g/m(2) with paricalcitol versus -4.85 [-9.89 to 1.10] g/m(2) with placebo). Changes in LV volume, ejection fraction, tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities, and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups. However, paricalcitol treatment significantly reduced intact parathyroid hormone (P<0.001) and alkaline phosphatase (P=0.001) levels as well as the number of cardiovascular-related hospitalizations compared with placebo. In conclusion, 52 weeks of treatment with oral paricalcitol (1 μg one time daily) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD.