tbuckley/cabot-search huggingface dataset:
Store-Operated Ca <sup>2+</sup> Entry Activates the CREB Transcription Factor in Vascular Smooth Muscle
Authors: Renee A. Pulver, Patricia Rose-Curtis, Michael W. Roe, George C. Wellman, Karen M. Lounsbury
Journal: Circulation Research (2004)

Ca 2+ -regulated gene transcription is a critical component of arterial responses to injury, hypertension, and tumor-stimulated angiogenesis. The Ca 2+ /cAMP response element binding protein (CREB), a transcription factor that regulates expression of many genes, is activated by Ca 2+ -induced phosphorylation. Multiple Ca 2+ entry pathways may contribute to CREB activation in vascular smooth muscle including voltage-dependent Ca 2+ channels and store-operated Ca 2+ entry (SOCE). To investigate a role for SOCE in CREB activation, we measured CREB phosphorylation using immunofluorescence, intracellular Ca 2+ levels using a fluorescence resonance energy transfer (FRET)–based Cameleon indicator, and c-fos transcription using RT-PCR. In this study, we report that SOCE activates CREB in both cultured smooth muscle cells and intact arteries. Depletion of intracellular Ca 2+ stores with thapsigargin increased nuclear phospho-CREB levels, intracellular Ca 2+ concentration, and transcription of c-fos . These effects were abolished by inhibiting SOCE through lowering extracellular Ca 2+ concentration or by application of 2-aminoethoxydiphenylborate and Ni 2+ . Inhibition of Ca 2+ influx through voltage-dependent Ca 2+ channels using nimodipine partially blocked intact artery responses, but was without effect in cultured smooth muscle cells. Our findings indicate that Ca 2+ entry through store-operated Ca 2+ channels leads to CREB activation, suggesting that SOCE contributes to the regulation of gene expression in vascular smooth muscle.
A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer
Authors: Kimberly L. Johung, Xiaopan Yao, Fangyong Li, James B. Yu, Scott N. Gettinger, Sarah Goldberg, Roy H. Decker, Judith A. Hess, Veronica L. Chiang, Joseph N. Contessa
Journal: Clinical Cancer Research (2013)

Non-small cell lung cancer (NSCLC) includes a spectrum of radiosensitive and radioresistant tumors. However, little is known about the molecular determinants of cellular radiation responses. We examined clinical outcomes after gamma knife radiotherapy for NSCLC intracranial metastases to evaluate the use of this model for determining radiosensitive tumor genotypes.Between 2005 and 2012, 239 patients with NSCLC were enrolled in a prospective gamma knife data repository. Molecular pathology regarding EGF receptor (EGFR), ALK, and KRAS mutation status was available for 81 patients. Local and distant brain control was determined for 79 patients with 469 brain metastases. Modified Cox proportional hazards models were established to evaluate local control for treated lesions after serial gamma knife treatments.In total, 11% of patients developed in-field recurrence. No patients with metastases from tumors with EGFR mutations (0/164 lesions) or EML4-ALK translocations (0/61 lesions) recurred in-field. In contrast, 19% of patients without these mutations and 18% of patients with KRAS mutations recurred in-field (10/139 and 3/105 lesions, respectively). Rates of distant brain recurrence did not significantly differ across tumor genotypes. The predicted median in-field local control was significantly longer for EGFR-mutant and ALK-translocated tumors compared with other patients with NSCLC (P < 0.001), whereas distant brain recurrence time was equivalent (P = 0.97). On multivariate analysis, EGFR mutation, ALK translocation, and metastasis size were independent predictors for superior local control after gamma knife treatment.This study suggests that EGFR kinase domain mutations and EML4-ALK translocations are radiosensitive NSCLC genotypes, and proposes a novel model to identify radiosensitive subtypes of NSCLC.
Assisted ventilation as an aid to exercise training: a mechanical doping?
Authors: N. Ambrosino
Journal: European Respiratory Journal (2005)

Exercise training as a part of multidisciplinary pulmonary rehabilitation can improve both exercise tolerance and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) 1. The following physiological changes contribute to these improvements: reduction of lactic acidosis; minute ventilation and heart rate for a given work rate; and enhanced activity of mitochondrial enzymes and capillary density in the trained muscles. Intensity of exercise training is of key importance. High-intensity training has improved both maximal and submaximal exercise tests and has induced both cardiorespiratory and peripheral muscle adaptations 2. Nevertheless, in patients with severe COPD, extreme breathlessness and/or peripheral muscle fatigue may prevent higher levels of intensity training. As a consequence of flow limitation, in order to cope with the increased ventilatory demands of exercise, these patients show a breathing pattern that ultimately places greater demands on their inspiratory muscles. Indeed, in these patients, a pattern of low tidal volume and high-frequency breathing is unlikely to be advantageous, but it is the only pattern available in the presence of expiratory flow limitation and dynamic hyperinflation. Increased inspiratory muscle work may contribute to dyspnoea and exercise limitation in such patients, even before their ventilatory ceiling is attained.

To the extent that intrinsic mechanical loading and functional inspiratory muscle weakness in COPD contribute to dyspnoea, assisted ventilation should provide symptomatic benefit by unloading and assisting such overburdened ventilatory muscles. Reducing exercise dyspnoea by assisted ventilation might allow for higher levels of exercise intensity. Several studies have examined the acute effects of different modalities of ventilatory assistance on dyspnoea and exercise tolerance in advanced COPD. The message of these physiological studies could be summarised as follows: assisted ventilation delivered as noninvasive positive pressure ventilation (NPPV), either as continuous positive airway pressure (CPAP), inspiratory pressure support (IPS) or proportional assist …
Ethnic Differences in the Prevalence of Diabetic Retinopathy in Persons With Diabetes When First Presenting at a Diabetes Clinic in South Africa
Authors: Rebecca L. Thomas, Larry Distiller, Stephen D. Luzio, Sharmistha Roy Chowdhury, Vanessa J. Melville, Brian Kramer, David R. Owens
Journal: Diabetes Care (2012)

To describe the prevalence and associated risk factors for diabetic retinopathy (DR) within a multiethnic population at presentation to a diabetes clinic in South Africa.Retinal photography was conducted using a nonmydriatic digital camera without mydriasis and graded by one of three senior graders. Logistic regression analyses were used to assess the association between any DR, referable DR, and clinical risk factors.A total of 1,537 persons with type 1 and 3,978 with type 2 diabetes were included. Prevalence of any DR in type 1 diabetes was 35.2% (background DR 26% and referable DR 9.2%) and in type 2 diabetes was 20.5% (14.1 and 6.4%, respectively). In type 1 diabetes, there was an increased risk of any DR in Asian Indians, whereas the risk of referable DR was increased for indigenous Africans compared with Caucasians. In type 2 diabetes, the risk was increased for all non-Caucasians compared with Caucasians. Longer duration of diabetes and elevated HbA(1c) were independently associated with any and referable DR in both type 1 and type 2 diabetes, with the addition of hypertension and smoking in type 1 diabetes when adjusted for age at diagnosis of diabetes, sex, and ethnicity.The prevalence of DR in this population from South Africa was similar to that reported globally; however, ethnic differences were observed. Increasing duration of diabetes and poor glycemic control were the strongest risk factors associated with any and referable DR in both type 1 and type 2 diabetes.
Response to insulin of the intact stomach in patients with duodenal ulcer
Authors: G. Gillespie, I. E. Gillespie, A. W. Kay
Journal: Gut (1969)

Insulin tests were performed on 47 duodenal ulcer patients with intact stomachs. Only 20 had a positive response to the test judged positive by the criteria of Hollander in the first 45 minutes after the insulin. Twenty became positive between 45 and 60 minutes, and in five the response was not noted until the second hour. Surprisingly, two patients had apparently negative responses to the insulin. While caution is necessary in comparing responses of the intact stomach to those after vagotomy operations, the occurrence of the ;late positive' and negative patterns of response to insulin in the intact stomach may give rise to reservations about the interpretation of these types of response after vagotomy.
Efficient inhibition of cisplatin-resistant human ovarian cancer growth and prolonged survival by gene transferred vesicular stomatitis virus matrix protein in nude mice
Authors: Q. Zhong, Y.-J. Wen, H.-S. Yang, H. Luo, A.-F. Fu, F. Yang, L.-J. Chen, X. Chen, X.-R. Qi, H.-G. Lin, Y. Wan, X.-C. Chen, Y.-Q. Wei, X. Zhao
Journal: Annals of Oncology (2008)
Regional lung function after pneumonectomy
Authors: D. R. Hall
Journal: Thorax (1974)

<b>Hall, D. R. (1974).</b><i>Thorax</i>, <b>29</b>, 425-431. <b>Regional lung function after pneumonectomy.</b> Regional lung function was studied with xenon-133 in 10 patients with bronchial carcinoma before and again three to six months after pneumonectomy. It was found that ventilation and perfusion were often considerably reduced in the tumour-bearing lung and that the greater part of the cardiac output had apparently been diverted to the unaffected lung before operation. The regional distribution of ventilation and perfusion in the lung remaining after surgery was essentially unchanged from that measured in the same lung preoperatively and no different from the pattern seen in 10 normal volunteers.
Preeclampsia, Placental Insufficiency, and Autism Spectrum Disorder or Developmental Delay
Authors: Cheryl K. Walker, Paula Krakowiak, Alice Baker, Robin L. Hansen, Sally Ozonoff, Irva Hertz-Picciotto
Journal: JAMA Pediatrics (2014)

Increasing evidence suggests that autism spectrum disorder (ASD) and many forms of developmental delay (DD) originate during fetal development. Preeclampsia may trigger aberrant neurodevelopment through placental, maternal, and fetal physiologic mechanisms.
State Scholarship, Loan Forgiveness, and Related Programs
Authors: Donald E. Pathman, Donald H. Taylor, Jr, Thomas R. Konrad, Tonya S. King, Tyndall Harris, Tim M. Henderson, James D. Bernstein, Thomas Tucker, Kathleen D. Crook, Cora Spaulding, Gary G. Koch
Journal: JAMA (2000)

In the mid-1980s, states expanded their initiatives of scholarships, loan repayment programs, and similar incentives to recruit primary care practitioners into underserved areas. With no national coordination or mandate to publicize these efforts, little is known about these state programs and their recent growth.To identify and describe state programs that provide financial support to physicians and midlevel practitioners in exchange for a period of service in underserved areas, and to begin to assess the magnitude of the contributions of these programs to the US health care safety net.Cross-sectional, descriptive study of data collected by telephone, mail questionnaires, and through other available documents, (eg, program brochures, Web sites).All state programs operating in 1996 that provided financial support in exchange for service in defined underserved areas to student, resident, and practicing physicians; nurse practitioners; physician assistants; and nurse midwives. We excluded local community initiatives and programs that received federal support, including that from the National Health Service Corps.Number and types of state support-for-service programs in 1996; trends in program types and numbers since 1990; distribution of programs across states; numbers of participating physicians and other practitioners in 1996; numbers in state programs relative to federal programs; and basic features of state programs.In 1996, there were 82 eligible programs operating in 41 states, including 29 loan repayment programs, 29 scholarship programs, 11 loan programs, 8 direct financial incentive programs, and 5 resident support programs. Programs more than doubled in number between 1990 (n = 39) and 1996 (n = 82). In 1996, an estimated 1306 physicians and 370 midlevel practitioners were serving obligations to these state programs, a number comparable with those in federal programs. Common features of state programs were a mission to influence the distribution of the health care workforce within their states' borders, an emphasis on primary care, and reliance on annual state appropriations and other public funding mechanisms.In 1996, states fielded an obligated primary care workforce comparable in size to the better-known federal programs. These state programs constitute a major portion of the US health care safety net, and their activities should be monitored, coordinated, and evaluated. State programs should not be omitted from listings of safety-net initiatives or overlooked in future plans to further improve health care access. JAMA. 2000;284:2084-2092.
Dietary fish oil and the severity of symptoms in patients with systemic lupus erythematosus.
Authors: A J Walton, M L Snaith, M Locniskar, A G Cumberland, W J Morrow, D A Isenberg
Journal: Annals of the Rheumatic Diseases (1991)

A prospective, double blind, cross over study assessing the effects of a low fat, high marine oil diet in 27 patients with active systemic lupus erythematosus has been performed. The patients were given 20 g daily of MaxEPA (eicosapentaenoic acid) or 20 g of olive oil (placebo) in matching capsules added to a standardised isoenergetic low fat diet. When individual outcome measures of the 17 patients who completed the full 34 week study were considered 14 who were receiving MaxEPA achieved useful or ideal status, whereas 13 receiving placebo were rated as worse or no change. The difference between the two types of capsule was statistically significant. No major side effects were noted, and it is suggested that dietary modification with additional marine oil may be a useful way of modifying disease activity in systemic lupus erythematosus.
Hip Implant Failure for Men and Women
Authors: Diana Zuckerman
Journal: JAMA Internal Medicine (2013)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Discontinuation of Evening Surgery
Authors: H. E. M. Welch
Journal: BMJ (1972)

objectivity in patients' management, so that the doctor might unwittingly be persuaded against a course of action which is ultimiately in the patient's own good.In a practice where it is taken for granted that not only may patients choose a doctor but also the doctor frequently may decide to confer with his colleagues in the presence of the patient, this danger is considerably diminished.So long as all partners are present in one central surgery at most, if not all, consul- ting times, so long as clinical notes are made concisely and clearly, and so long as regular (preferably daily) formal conversations take place between the partners in addition to in- surgery discussions, then we believe that encouraging the patients to consult any of the doctors can only enhance the standard of medical care in general practice.-Weare, etc.,
Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial
Authors: Enrique F Schisterman, Robert M Silver, Laurie L Lesher, David Faraggi, Jean Wactawski-Wende, Janet M Townsend, Anne M Lynch, Neil J Perkins, Sunni L Mumford, Noya Galai
Journal: The Lancet (2014)
Central vascular pressure measurements during exercise in COPD: How to handle the respirophasic changes?
Authors: Bart Boerrigter, Aaron Waxman, Nico Westerhof, Anton Vonk-Noordegraaf, David Systrom
Journal: European Respiratory Journal (2013)

Introduction: Respirophasic changes are a major confounder when evaluating central hemodynamics during exercise. We studied the accuracy of four different methods to assess mean pulmonary artery pressure (mPAP) and pulmonary capillary wedge pressure (PCWP) in case of heavy respiratory swings.  Methods: Central hemodynamics measured simultaneously with esophageal pressure during exercise in 30 COPD-patients. mPAP and PCWP were assessed at end-expiration, averaged over the respiratory cycle and corrected with a from the right atrial pressure (RAP) waveform estimated intrathoracic pressure and compared with the transmural pressures.  Results: Bland-Altman analyses showed the best agreement of mPAP averaged over the respiratory cycle (bias: 2.5 mmHg, limits of agreement: -6.0 to 11.8) and when corrected with the nadir of RAP (bias: -3.6 mmHg, limits: -11.2 to 3.9). Measuring mPAP at end-expiration (bias: 10.3mmHg, limits: 0.5 to 20.3) and mPAP corrected with the RAP-swing (bias: -9.3mmHg, limits: -19.8 to 2.1) resulted in lower levels of agreement.  Conclusion: Central hemodynamics measured at end-expiration leads to an overestimation of intravascular pressures in exercising COPD-patients. Averaging pressures over the respiratory cycle or using the right atrial pressure waveform to estimate and correct for intrathoracic pressure leads to better estimations of intravascular pressure.
William Osler and the jubjub of ethics; or how to teach medical ethics in the 21st century
Authors: Daniel K Sokol
Journal: Journal of the Royal Society of Medicine (2007)

William Osler (1849-1919) was arguably the world's most famous physician at the turn of the 20th century. Although his writings are diverse and prolific, there is remarkably little on the subject of medical ethics.1,2

This absence is not, I believe, a result of Osler's lack of interest in matters medico-ethical, even at a time when such issues were perhaps not as complex as they are today. The reason is that his focus was on character and virtues, rather than on particular moral problems and individual actions. His moral outlook was predominantly agent-based, not act-based. He was concerned with the ‘good’ doctor, the ‘good’ teacher, the ‘good’ student, and these were frequently defined by their desirable habits, dispositions, and character traits.
Therapies for Active Rheumatoid Arthritis after Methotrexate Failure
Authors: James R. O'Dell, Ted R. Mikuls, Thomas H. Taylor, Vandana Ahluwalia, Mary Brophy, Stuart R. Warren, Robert A. Lew, Amy C. Cannella, Gary Kunkel, Ciaran S. Phibbs, Aslam H. Anis, Sarah Leatherman, Edward Keystone
Journal: New England Journal of Medicine (2013)

Few blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate--a common scenario in the management of rheumatoid arthritis.We conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48.Both groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications.With respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275.)
Calcium Mediates Glomerular Filtration through Calcineurin and mTORC2/Akt Signaling
Authors: John Vassiliadis, Christina Bracken, Douglas Matthews, Stephen O'Brien, Susan Schiavi, Stefan Wawersik
Journal: Journal of the American Society of Nephrology (2011)

Alterations to the structure of the glomerular filtration barrier lead to effacement of podocyte foot processes, leakage of albumin, and the development of proteinuria. To better understand the signaling pathways involved in the response of the glomerular filtration barrier to injury, we studied freshly isolated rat glomeruli, which allows for the monitoring and pharmacologic manipulation of early signaling events. Administration of protamine sulfate rapidly damaged the isolated glomeruli, resulting in foot process effacement and albumin leakage. Inhibition of calcium channels and chelation of extracellular calcium reduced protamine sulfate-induced damage, suggesting that calcium signaling plays a critical role in the initial stages of glomerular injury. Calcineurin inhibitors (FK506 and cyclosporine A) and the cathepsin L inhibitor E64 all inhibited protamine sulfate-mediated barrier changes, which suggests that calcium signaling acts, in part, through calcineurin- and cathepsin L-dependent cleavage of synaptopodin, a regulator of actin dynamics. The mTOR inhibitor rapamycin also protected glomeruli, demonstrating that calcium signaling has additional calcineurin-independent components. Furthermore, activation of Akt through mTOR had a direct role on glomerular barrier integrity, and activation of calcium channels mediated this process, likely independent of phosphoinositide 3-kinase. Taken together, these results demonstrate the importance of calcium and related signaling pathways in the structure and function of the glomerular filtration barrier.