tbuckley/cabot-search huggingface dataset:
Targeting myocardial remodelling to develop novel therapies for heart failure
Authors: Guido Tarone, Jean‐Luc Balligand, Johann Bauersachs, Angela Clerk, Leon De Windt, Stephane Heymans, Denise Hilfiker‐Kleiner, Emilio Hirsch, Guido Iaccarino, Ralph Knöll, Adelino F. Leite‐Moreira, André P. Lourenço, Manuel Mayr, Thomas Thum, Carlo G. Tocchetti
Journal: European Journal of Heart Failure (2014)
Direct determination of the driving forces for taurocholate uptake into rat liver plasma membrane vesicles.
Authors: M C Duffy, B L Blitzer, J L Boyer
Journal: Journal of Clinical Investigation (1983)

To determine directly the driving forces for bile acid entry into the hepatocyte, the uptake of [3H]taurocholic acid into rat liver plasma membrane vesicles was studied. The membrane preparation contained predominantly right-side-out vesicles, and was highly enriched in plasma membrane marker enzymes. The uptake of taurocholate at equilibrium was inversely related to medium osmolarity, indicating transport into an osmotically sensitive space. In the presence of an inwardly directed sodium gradient (NaCl or sodium gluconate), the initial rate of uptake was rapid and taurocholate was transiently accumulated at a concentration twice that at equilibrium (overshoot). Other inwardly directed cation gradients (K+, Li+, choline+) or the presence of sodium in the absence of a gradient (Na+ equilibrated) resulted in a slower initial uptake rate and did not sustain an overshoot. Bile acids inhibited sodium-dependent taurocholate uptake, whereas bromsulphthalein inhibited both sodium-dependent and sodium-independent uptake and D-glucose had no effect on uptake. Uptake was temperature dependent, with maximal overshoots occurring at 25 degrees C. Imposition of a proton gradient across the vesicle (pHo less than pHi) in the absence of a sodium gradient failed to enhance taurocholate uptake, indicating that double ion exchange (Na+-H+, OH- -anion) is unlikely. Creation of a negative intravesicular potential by altering accompanying anions or by valinomycin-induced K+-diffusion potentials did not enhance taurocholate uptake, suggesting an electroneutral transport mechanism. The kinetics of taurocholate uptake demonstrated saturability with a Michaelis constant at 52 microM and maximum velocity of 4.5 nmol X mg-1 X protein X min-1. These studies provide definitive evidence for a sodium gradient-dependent, carrier-mediated, electrically neutral transport mechanism for hepatic taurocholate uptake. These findings are consistent with a model for bile secretion in which the basolateral enzyme Na+,K+-ATPase provides the driving force for "uphill" bile acid transport by establishing a trans-membrane sodium gradient.
Combination Therapy With Gefitinib and Rofecoxib in Patients With Platinum-Pretreated Relapsed Non–Small-Cell Lung Cancer
Authors: Kenneth J. O'Byrne, Sarah Danson, David Dunlop, Nick Botwood, Fumiko Taguchi, David Carbone, Malcolm Ranson
Journal: Journal of Clinical Oncology (2007)

In non-small-cell lung cancer (NSCLC), the epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) play major roles in tumorigenesis. This phase I/II study evaluated combined therapy with the EGFR tyrosine kinase inhibitor (TKI) gefitinib and the COX-2 inhibitor rofecoxib in platinum-pretreated, relapsed, metastatic NSCLC (n = 45).Gefitinib 250 mg/d was combined with rofecoxib (dose escalated from 12.5 to 25 to 50 mg/d through three cohorts, each n = 6). Because the rofecoxib maximum-tolerated dose was not reached, the 50 mg/d cohort was expanded for efficacy evaluation (n = 33).Among the 42 assessable patients, there was one complete response (CR) and two partial responses (PRs) and 12 patients with stable disease (SD); disease control rate was 35.7% (95% CI, 21.6% to 52.0%). Median time to tumor progression was 55 days (95% CI, 47 to 70 days), and median survival was 144 days (95% CI, 103 to 190 days). In a pilot study, matrix-assisted laser desorption/ionization (MALDI) proteomics analysis of baseline serum samples could distinguish patients with an objective response from those with SD or progressive disease (PD), and those with disease control (CR, PR, and SD) from those with PD. The regimen was generally well tolerated, with predictable toxicities including skin rash and diarrhea.Gefitinib combined with rofecoxib provided disease control equivalent to that expected with single-agent gefitinib and was generally well tolerated. Baseline serum proteomics may help identify those patients most likely to benefit from EGFR TKIs.
Functional Co-Primary Measures for Clinical Trials in Schizophrenia: Results From the MATRICS Psychometric and Standardization Study
Authors: Michael F. Green, Keith H. Nuechterlein, Robert S. Kern, Lyle E. Baade, Wayne S. Fenton, James M. Gold, Richard S.E. Keefe, Raquelle Mesholam-Gately, Larry J. Seidman, Ellen Stover, Stephen R. Marder
Journal: American Journal of Psychiatry (2008)

Objective: During the consensus meetings of the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia (NIMH-MATRICS) Initiative, the U.S. Food and Drug Administration took the position that a drug for this purpose should show changes on 1) an accepted consensus cognitive performance measure and 2) an additional measure (i.e., a co-primary) that is considered functionally meaningful. The goal of the current study was to describe steps to evaluate four potential co-primary measures for psychometric properties and validity. Method: As part of the five-site MATRICS Psychometric and Standardization Study (PASS), two measures of functional capacity and two interview-based measures of cognition were evaluated in 176 patients with schizophrenia (167 of these patients were retested 4 weeks later). Results: Data are presented for each co-primary measure for test-retest reliability, utility as a repeated measure, relationship to cognitive performance, relationship to functioning, tolerability/practicality, and number of missing data. Conclusions: Psychometric properties of all of the measures were considered acceptable, and the measures were generally comparable across the various criteria, except that the functional capacity measures had stronger relationships to cognitive performance and fewer missing data. The development and evaluation of potential co-primary measures is still at an early stage, and it was decided not to endorse a single measure for clinical trials at this point. The current findings offer the initial steps to identify functionally meaningful co-primary measures in this area and will help to guide further evaluation of such measures.
Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists
Authors: J Askling
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s. <b>Objective:</b> To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials. <b>Methods:</b> A population based study of three RA cohorts (one prevalent, admitted to hospital 1990–2003 (n = 53 067), one incident, diagnosed 1995–2003 (n = 3703), and one treated with TNF antagonists 1999–2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003. <b>Results:</b> With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20–50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (−20%) and colorectal cancer (−25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA. <b>Conclusion:</b> The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.
National Burden of Invasive Methicillin-Resistant<i>Staphylococcus aureus</i>Infection
Authors: Preeti N. Malani
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients
Authors: Pierre Singer, Ronit Anbar, Jonathan Cohen, Haim Shapiro, Michal Shalita-Chesner, Shaul Lev, Elad Grozovski, Miryam Theilla, Sigal Frishman, Zecharia Madar
Journal: Intensive Care Medicine (2011)
The British Thoracic Society guideline on pulmonary rehabilitation in adults: your opinion is noted
Authors: Charlotte E Bolton, John D Blakey, Mike D Morgan
Journal: Thorax (2014)

We thank Professors McConnell and Gosselink for their interest in the British Thoracic Society (BTS) pulmonary rehabilitation guideline.1 ,2 We welcome the opportunity to highlight the robust, unbiased approach that the guideline development group (GDG) has followed in making their recommendations which have been accredited by National Institute of Health and Care Excellence. This process, according to the BTS production manual, is described in the guideline methodology.2 It included initial training, each article being considered by at least two GDG members, independent peer review at multiple stages and consultation periods for …
Finalisation and validation of the rheumatoid arthritis impact of disease score, a patient-derived composite measure of impact of rheumatoid arthritis: a EULAR initiative
Authors: L Gossec, S Paternotte, G J Aanerud, A Balanescu, D T Boumpas, L Carmona, M de Wit, B A C Dijkmans, M Dougados, M Englbrecht, F Gogus, T Heiberg, C Hernandez, J R Kirwan, E Martin Mola, M Matucci Cerinic, K Otsa, G Schett, M Scholte-Voshaar, T Sokka, G von Krause, G A Wells, T K Kvien
Journal: Annals of the Rheumatic Diseases (2011)

Objective A patient-derived composite measure of the impact of rheumatoid arthritis (RA), the rheumatoid arthritis impact of disease (RAID) score, takes into account pain, functional capacity, fatigue, physical and emotional wellbeing, quality of sleep and coping. The objectives were to finalise the RAID and examine its psychometric properties. Methods An international multicentre cross-sectional and longitudinal study of consecutive RA patients from 12 European countries was conducted to examine the psychometric properties of the different combinations of instruments that might be included within the RAID combinations scale (numeric rating scales (NRS) or various questionnaires). Construct validity was assessed cross-sectionally by Spearman correlation, reliability by intraclass correlation coefficient (ICC) in 50 stable patients, and sensitivity to change by standardised response means (SRM) in 88 patients whose treatment was intensified. Results 570 patients (79% women, mean±SD age 56±13 years, disease duration 12.5±10.3 years, disease activity score (DAS28) 4.1±1.6) participated in the validation study. NRS questions performed as well as longer combinations of questionnaires: the final RAID score is composed of seven NRS questions. The final RAID correlated strongly with patient global (R=0.76) and significantly also with other outcomes (DAS28 R=0.69, short form 36 physical −0.59 and mental −0.55, p&lt;0.0001 for all). Reliability was high (ICC 0.90; 95% CI 0.84 to 0.94) and sensitivity to change was good (SRM 0.98 (0.96 to 1.00) compared with DAS28 SRM 1.06 (1.01 to 1.11)). Conclusion The RAID score is a patient-derived composite score assessing the seven most important domains of impact of RA. This score is now validated; sensitivity to change should be further examined in larger studies.
Treatment of Erectile Dysfunction in Men With Depressive Symptoms: Results of a Placebo-Controlled Trial With Sildenafil Citrate
Authors: Stuart N. Seidman, Steven P. Roose, Matthew A. Menza, Ridwan Shabsigh, Raymond C. Rosen
Journal: American Journal of Psychiatry (2001)

Depressed men commonly have erectile dysfunction, and men with erectile dysfunction are frequently depressed. Since the etiologic and modulatory relationships between depression and erectile dysfunction have been poorly characterized, a 12-week, randomized, double-blind, placebo-controlled trial was conducted at 20 urologic clinics to evaluate the effects of sildenafil treatment in men with erectile dysfunction and mild-to-moderate comorbid depressive illness.Men (N=152, mean age=56 years) with erectile dysfunction for > or =6 months (mean=5.7 years), a DSM-IV diagnosis of depressive disorder not otherwise specified, and a Hamilton Depression Rating Scale score > or =12 (mean at baseline=16.9) were randomly assigned to flexible-dose treatment with sildenafil citrate or matching placebo. Interviewer-rated and self-report instruments were used to assess changes in sexual function, depressive symptoms, and quality of life. Conservative criteria were used to classify erectile dysfunction treatment response and nonresponse.Sildenafil was strongly associated with erectile dysfunction treatment response. Fifty-eight men met the conservative criteria for response (48 given sildenafil, 10 given placebo), and 78 men did not respond (18 given sildenafil, 60 given placebo). Mean decreases of 10.6 and 2.3 in Hamilton depression scale scores were seen in treatment responders and nonresponders, respectively; 76% of treatment responders showed a > or =50% decline in Hamilton depression scale score versus 14% of nonresponders. Quality of life was similarly improved in treatment responders.Sildenafil is efficacious for erectile dysfunction in men with mild-to-moderate depressive illness. Improvement of erectile dysfunction is associated with marked improvement in depressive symptoms and quality of life.
Delayed Time to Defibrillation after In-Hospital Cardiac Arrest
Authors: Paul S. Chan, Harlan M. Krumholz, Graham Nichol, Brahmajee K. Nallamothu
Journal: New England Journal of Medicine (2008)

Expert guidelines advocate defibrillation within 2 minutes after an in-hospital cardiac arrest caused by ventricular arrhythmia. However, empirical data on the prevalence of delayed defibrillation in the United States and its effect on survival are limited.
The Demographic Histories of the M and S Molecular Forms of Anopheles gambiae s.s.
Authors: Jacob E. Crawford, Brian P. Lazzaro
Journal: Molecular Biology and Evolution (2010)

Anopheles gambiae is a primary vector of Plasmodium falciparum, a human malaria parasite that causes over a million deaths each year in sub-Saharan Africa. Population genetic tests have been employed to detect natural selection at suspected A. gambiae antimalaria genes, but these tests have generally been compromised by the lack of demographically correct null models. Here, we used a coalescent simulation approach within a maximum likelihood framework to fit population growth, bottleneck, and migration models to polymorphism data from Cameroonian A. gambiae. The best-fit models for both the "M" and the "S" molecular forms of A. gambiae included ancient population growth and a high rate of migration from an unsampled subpopulation. After correcting for differences in effective population size, our models suggest that the molecular forms expanded at different times and both expansions significantly predate the advent of agriculture. We show that correcting null models for demography increases the power to detect natural selection in A. gambiae.
Renin-Aldosterone Paradox and Perturbed Blood Volume Regulation Underlying Postural Tachycardia Syndrome
Authors: Satish R. Raj, Italo Biaggioni, Paula C. Yamhure, Bonnie K. Black, Sachin Y. Paranjape, Daniel W. Byrne, David Robertson
Journal: Circulation (2005)

Patients with postural tachycardia syndrome (POTS) experience considerable disability, but in most, the pathophysiology remains obscure. Plasma volume disturbances have been implicated in some patients. We prospectively tested the hypothesis that patients with POTS are hypovolemic compared with healthy controls and explored the role of plasma renin activity and aldosterone in the regulation of plasma volume.Patients with POTS (n=15) and healthy controls (n=14) underwent investigation. Heart rate (HR), blood pressure (BP), plasma renin activity, and aldosterone were measured with patients both supine and upright. Blood volumes were measured with 131I-labeled albumin and hematocrit. Patients with POTS had a higher orthostatic increase in HR than controls (51+/-18 versus 16+/-10 bpm, P<0.001). Patients with POTS had a greater deficit in plasma volume (334+/-187 versus 10+/-250 mL, P<0.001), red blood cell volume (356+/-128 versus 218+/-140 mL, P=0.010), and total blood volume (689+/-270 versus 228+/-353 mL, P<0.001) than controls. Despite the lower plasma volume in patients with POTS, there was not a compensatory increase in plasma renin activity (0.79+/-0.58 versus 0.79+/-0.74 ng x mL(-1) x h(-1), P=0.996). There was a paradoxically low level of aldosterone in the patients with POTS (190+/-140 pmol/L versus 380+/-230 pmol/L; P=0.017).Patients with POTS have paradoxically unchanged plasma renin activity and low aldosterone given their marked reduction in plasma volume. These patients also have a significant red blood cell volume deficit, which is regulated by the renal hormone erythropoietin. These abnormalities suggest that the kidney may play a key role in the pathophysiology of POTS.
End Points and United States Food and Drug Administration Approval of Oncology Drugs
Authors: John R. Johnson, Grant Williams, Richard Pazdur
Journal: Journal of Clinical Oncology (2003)

To summarize the end points used by the United States Food and Drug Administration (FDA) to approve new cancer drug applications over the last 13 years.The FDA granted marketing approval to 71 oncology drug applications between January 1, 1990, and November 1, 2002. The end points used as the approval basis for each application are presented, and the rationale for each end point is discussed.The FDA grants either regular marketing approval or accelerated marketing approval for oncology drug applications. Regular approval is based on end points that demonstrate that the drug provides a longer life, a better life, or a favorable effect on an established surrogate for a longer life or a better life. Accelerated approval (AA) is based on a surrogate end point that is less well established but that is reasonably likely to predict a longer or a better life. Tumor response was the approval basis in 26 of 57 regular approvals, supported by relief of tumor-specific symptoms in nine of these 26 regular approvals. Relief of tumor-specific symptoms provided critical support for approval in 13 of 57 regular approvals. Approval was based on tumor response in 12 of 14 AAs.End points other than survival were the approval basis for 68% (39 of 57) of oncology drug marketing applications granted regular approval and for all 14 applications granted accelerated approval from January 1, 1990, to November 1, 2002.
Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level
Authors: Chien-Jen Chen
Journal: JAMA (2006)

ContextSerum hepatitis B virus (HBV) DNA level is a marker of viral replication and efficacy of antiviral treatment in individuals with chronic hepatitis B.ObjectiveTo evaluate the relationship between serum HBV DNA level and risk of hepatocellular carcinoma.Design, Setting, and ParticipantsProspective cohort study of 3653 participants (aged 30-65 years), who were seropositive for the hepatitis B surface antigen and seronegative for antibodies against the hepatitis C virus, recruited to a community-based cancer screening program in Taiwan between 1991 and 1992.Main Outcome MeasureIncidence of hepatocellular carcinoma during follow-up examination and by data linkage with the national cancer registry and the death certification systems.ResultsThere were 164 incident cases of hepatocellular carcinoma and 346 deaths during a mean follow-up of 11.4 years and 41 779 person-years of follow-up. The incidence of hepatocellular carcinoma increased with serum HBV DNA level at study entry in a dose-response relationship ranging from 108 per 100 000 person-years for an HBV DNA level of less than 300 copies/mL to 1152 per 100 000 person-years for an HBV DNA level of 1 million copies/mL or greater. The corresponding cumulative incidence rates of hepatocellular carcinoma were 1.3% and 14.9%, respectively. The biological gradient of hepatocellular carcinoma by serum HBV DNA levels remained significant (P&lt;.001) after adjustment for sex, age, cigarette smoking, alcohol consumption, serostatus for the hepatitis B e antigen (HBeAg), serum alanine aminotransferase level, and liver cirrhosis at study entry. The dose-response relationship was most prominent for participants who were seronegative for HBeAg with normal serum alanine aminotransferase levels and no liver cirrhosis at study entry. Participants with persistent elevation of serum HBV DNA level during follow-up had the highest hepatocellular carcinoma risk.ConclusionElevated serum HBV DNA level (≥10 000 copies/mL) is a strong risk predictor of hepatocellular carcinoma independent of HBeAg, serum alanine aminotransferase level, and liver cirrhosis.