tbuckley/cabot-search huggingface dataset:
Amplified in Breast Cancer 1 in Human Epidermal Growth Factor Receptor–Positive Tumors of Tamoxifen-Treated Breast Cancer Patients
Authors: Tove Kirkegaard, Liane M. McGlynn, Fiona M. Campbell, Sven Müller, Sian M. Tovey, Barbara Dunne, Kirsten V. Nielsen, Timothy G. Cooke, John M.S. Bartlett
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Amplified in breast cancer 1 (AIB1) is a member of the p160/steroid receptor coactivators family and is involved in estrogen-dependent gene transcription by reducing the antagonistic activity of tamoxifen-bound estrogen receptor-α (ER-α). The present study was carried out to test the hypothesis that AIB1 protein expression and/or gene amplification mediates tamoxifen resistance in breast cancer. Experimental Design: Immunohistochemistry using AIB1 antibody and fluorescence in situ hybridization using probes specific for AIB1 and chromosome 20 was done on 402 ER-α–positive tamoxifen-treated breast cancers. Results: AIB1 overexpression was not associated with relapse during treatment with tamoxifen. In contrast, high AIB1 expression in patients with human epidermal growth factor receptor (HER) 2– and HER3-overexpressing tumors or tumors expressing one or more of HER1, HER2, or HER3 (HER1-3 positive) was associated with an increased risk of relapse on tamoxifen [hazard ratio, 2.20; 95% confidence interval, 1.07-3.52 (P = 0.0416); hazard ratio, 2.42; 95% confidence interval, 1.32-4.43 (P = 0.0030), respectively]. AIB1 gene amplification was observed in 18 of 362 (5%) patients. High AIB1 gene copy number had no effect on overall or disease-free survival. Conclusions: Data presented here support a role for AIB1 expression on relapse during tamoxifen treatment in hormone-responsive HER-expressing clinical breast cancers and support clinical evidence, suggesting a cross-talk between ER-α and growth factor receptor pathways through changes in expression of specific coactivator proteins, such as AIB1. This study highlights the potential that tumor profiling, using multiple markers of treatment response, may improve patient selection for endocrine treatment, such as tamoxifen or aromatase inhibitors.
One Hundred Years of Chronic Obstructive Pulmonary Disease
Authors: Alfred P. Fishman
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Chronic obstructive pulmonary disease (COPD) is a new name for an old malady. The ancients included the disease under the rubric of “catarrh.” In modern times, COPD has come to signify a mixture of chronic bronchitis, asthmatic bronchitis, and emphysema (1, 2). Rarification of the lung in emphysema may progress to form bullae (Figure 1). Cigarette smoking has long been recognized as the predominant etiologic agent. Arterial hypoxemia, a frequent complication of COPD, can lead to pulmonary hypertension and cor pulmonale (Figure 2). Michaud, Murray, and Bloom have recently underscored the enormous national and global impact of COPD (3). The disease is the fourth most common cause of death, and the harmful effects of the disease extend beyond the lungs. The disease is prevalent worldwide and in 1993, the cost of health care for COPD was estimated to be of the order of $15 billion. Arterial hypoxemia, a frequent complication of lung disease, can lead to pulmonary hypertension and cor pulmonale. Neither the prevalence of the disease nor the mortality that it causes show signs of slackening.
Malignant melanoma in childhood
Authors: S.E. HANDFIELD-JONES, N.P. SMITH
Journal: British Journal of Dermatology (1996)

Malignant melanoma (MM) is rare in childhood. We report 24 cases of MM in children 16 years old or less, whose histopathological specimens were referred to our department from 1981 to 1993. In only three cases was the diagnosis of MM made clinically. In some cases histological distinction from benign Spitz naevi was difficult, but other cases were referred because of a reluctance to diagnose MM in a child. One child died of disseminated disease, two developed nodal metastases and two developed local recurrence. Of all the lesions, the one which was considered to show the least difference from a benign naevus histologically occurred in the child who died. Awareness that MM, although rare, does occur in childhood, is vital. However, diagnosis is difficult, both clinically and histopathologically.
Improved hemodynamic function during hypoxia with Carbicarb, a new agent for the management of acidosis.
Authors: R M Bersin, A I Arieff
Journal: Circulation (1988)

Carbicarb is a mixture of Na2CO3/NaHCO3 that buffers similarly to NaHCO3, but without net generation of CO2. We studied the effects of carbicarb in an animal preparation of hypoxic lactic acidosis (HLA). HLA was induced by ventilating dogs with an hypoxic gas mixture (8% O2/92% N2). Dogs with HLA (n = 28) were then treated with 2.5 meq/kg of either NaHCO3 or carbicarb over 1 hr. Measurements were made, after 1 hr of hypoxia and 1 hr of therapy, of: cardiac hemodynamics, blood gases, liver intracellular pH (pHi), oxygen consumption, and regional lactate production. After therapy, the arterial pH rose with carbicarb (7.22 to 7.27, p less than .01), and fell with NaHCO3 (7.18 to 7.13, p less than .01). Mixed venous PCO2 did not change with carbicarb but increased with NaHCO3 (p less than .05). Arterial lactates stabilized with carbicarb but rose with NaHCO3 (by 3.1 mmol/liter, p less than .005). Lactate use by muscle, gut, and liver all improved with carbicarb and decreased with NaHCO3. The liver pHi (normal = 6.99, hypoxia = 6.80) improved with carbicarb (to 6.92), but decreased further with NaHCO3 (to 6.40). Muscle O2 consumption rose with carbicarb, whereas it decreased with NaHCO3. Arterial pressure fell less with carbicarb (-12 vs -46 mm Hg, p less than .006) and the cardiac output was stable with carbicarb but decreased with NaHCO3 (from 143 to 98 ml/kg/min, p less than .004). Stroke volume also improved with carbicarb but there was no change in pulmonary capillary wedge pressure, suggesting that carbicarb had a beneficial effect on myocardial contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
HIV prevention in Mexican schools: prospective randomised evaluation of intervention
Authors: Dilys Walker, Juan Pablo Gutierrez, Pilar Torres, Stefano M Bertozzi
Journal: BMJ (2006)

To assess effects on condom use and other sexual behaviour of an HIV prevention programme at school that promotes the use of condoms with and without emergency contraception.Cluster randomised controlled trial.40 public high schools in the state of Morelos, Mexico.10 954 first year high school students.Schools were randomised to one of three arms: an HIV prevention course that promoted condom use, the same course with emergency contraception as back-up, or the existing sex education course. Self administered anonymous questionnaires were completed at baseline, four months, and 16 months. Students at intervention schools received a 30 hour course (over 15 weeks) on HIV prevention and life skills, designed in accordance with guidelines of the joint United Nations programme on HIV/AIDS. Two extra hours of education on emergency contraception were given to students in the condom promotion with contraception arm.Primary outcome measure was reported condom use. Other outcomes were reported sexual activity; knowledge and attitudes about HIV and emergency contraception; and attitudes and confidence about condom use.Intervention did not affect reported condom use. Knowledge of HIV improved in both intervention arms and knowledge of emergency contraception improved in the condom promotion with contraception arm. Reported sexual behaviour was similar in the intervention arms and the control group.A rigorously designed, implemented, and evaluated HIV education course based in public high schools did not reduce risk behaviour, so such courses need to be redesigned and evaluated. Addition of emergency contraception did not decrease reported condom use or increase risky sexual behaviour but did increase reported use of emergency contraception.
The biological and immunological properties of pork and beef insulin, proinsulin, and connecting peptides
Authors: Abbas E. Kitabchi
Journal: Journal of Clinical Investigation (1970)

The recently discovered hormone precursors, pork and beef proinsulins, their respective connecting peptides, and beef proinsulin intermediates have been compared to insulin in their ability to stimulate the conversion of glucose-U-(14)C to (14)CO(2) and lipids in isolated fat cells. The concentrations of beef and pork proinsulins required to achieve the same biological effect were respectively, 15 and 10 times that of insulin. Beef proinsulin intermediates required only 2.6 times the concentration of insulin for the same effect. Pork and beef connecting peptides in high or low concentrations alone or in combination with proinsulin, insulin, or proinsulin intermediates showed no biological effect on the isolated fat cell system. The insulin-like activity of beef and pork proinsulins on the isolated fat cell system was not abolished with pancreatic trypsin or kallikrein inhibitors. Pork insulin antiserum inhibited the biological activity of pork insulin and proinsulin as well as that of beef insulin or proinsulin. Pork proinsulin antiserum also inhibited the insulin-like activity of both pork insulin and proinsulin. By the radioimmunoassay method, pork insulin antiserum bound only (1/4) to [unk] as much proinsulin as insulin. Beef proinsulin intermediates, on the other hand, were found to react with the pork insulin antiserum to an extent nearly equal to that of insulin. These data suggest that (a) proinsulin exhibits its effect on the isolated fat cells independent of its conversion to insulin, (b) connecting peptides have no biological effect under present experimental conditions, and (c) in comparison to insulin, immunological reactivity of proinsulin is greater than its biological activity using our pork insulin antiserum; thus, the comparison of antibody specificity with the fat cell receptor specificity suggests that the biological site of action is different from the immunologic site.
What Constitutes an Adequate Evaluation of Device-Guided Breathing?—Reply
Authors: Gijs W. D. Landman, Kornelis J. J. van Hateren, Nanne Kleefstra
Journal: JAMA Internal Medicine (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 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
Electronic Trigger-Based Intervention to Reduce Delays in Diagnostic Evaluation for Cancer: A Cluster Randomized Controlled Trial
Authors: Daniel R. Murphy, Louis Wu, Eric J. Thomas, Samuel N. Forjuoh, Ashley N.D. Meyer, Hardeep Singh
Journal: Journal of Clinical Oncology (2015)

Purpose We tested whether prospective use of electronic health record-based trigger algorithms to identify patients at risk of diagnostic delays could prevent delays in diagnostic evaluation for cancer. Methods We performed a cluster randomized controlled trial of primary care providers (PCPs) at two sites to test whether triggers that prospectively identify patients with potential delays in diagnostic evaluation for lung, colorectal, or prostate cancer can reduce time to follow-up diagnostic evaluation. Intervention steps included queries of the electronic health record repository for patients with abnormal findings and lack of associated follow-up actions, manual review of triggered records, and communication of this information to PCPs via secure e-mail and, if needed, phone calls to ensure message receipt. We compared times to diagnostic evaluation and proportions of patients followed up between intervention and control cohorts based on final review at 7 months. Results We recruited 72 PCPs (36 in the intervention group and 36 in the control group) and applied the trigger to all patients under their care from April 20, 2011, to July 19, 2012. Of 10,673 patients with abnormal findings, the trigger flagged 1,256 patients (11.8%) as high risk for delayed diagnostic evaluation. Times to diagnostic evaluation were significantly lower in intervention patients compared with control patients flagged by the colorectal trigger (median, 104 v 200 days, respectively; n = 557; P &lt; .001) and prostate trigger (40% received evaluation at 144 v 192 days, respectively; n = 157; P &lt; .001) but not the lung trigger (median, 65 v 93 days, respectively; n = 19; P = .59). More intervention patients than control patients received diagnostic evaluation by final review (73.4% v 52.2%, respectively; relative risk, 1.41; 95% CI, 1.25 to 1.58). Conclusion Electronic trigger-based interventions seem to be effective in reducing time to diagnostic evaluation of colorectal and prostate cancer as well as improving the proportion of patients who receive follow-up. Similar interventions could improve timeliness of diagnosis of other serious conditions.
A Rose by Any Other Name: Pain Contracts/Agreements
Authors: Richard Payne, Evan Anderson, Robert Arnold, Lennie Duensing, Aaron Gilson, Carmen Green, Carlton Haywood, Steve Passik, Ben Rich, Lisa Robin, Nick Shuler, Myra Christopher
Journal: The American Journal of Bioethics (2010)

Pain is the most common reason people seek medical advice. It is estimated that more than 50 million Americans suffer from chronic pain, e.g., nonmalignant, benign, or non-cancer-related pain, caus...
Electrophysiological Challenges of Cell-Based Myocardial Repair
Authors: Huei-Sheng Vincent Chen, Changsung Kim, Mark Mercola
Journal: Circulation (2009)

C ardiovascular diseases remain the major cause of death in the Western world. 1 Stem and progenitor cell (SPC)based therapies in animal models and human trials in recent years have suggested promising therapeutic potential and drawn intense public interest.Possible beneficial mechanisms of cell-based therapies include generation of new and mature ventricular cardiomyocytes (cardiomyogenesis), recruitment of endogenous SPCs for cardiomyogenesis, and salvage of native myocardium through paracrine, angiogenic, and antiapoptotic effects. 2,33][4][5] Here we discuss potential electrophysiological challenges and arrhythmic risks posed by cell therapies designed to replace damaged myocardium.Although adverse outcomes after cell therapies, such as lethal arrhythmias, occurred in early clinical trials of skeletal myoblast transplantation, 5-8 recent clinical trials using various sources of SPCs, novel modes of cell delivery, better cell selection, and different timing of cell transplantation did not show any significant increase in arrhythmic incidence.It is tempting to conclude on this basis that cell-based therapies are "safe" and nonarrhythmogenic (reviewed in References 2 and 4); however, the negligible production of new cardiomyocytes documented for many SPCs employed makes it difficult to extrapolate their safety records toward future trials in which substantial numbers of new cardiomyocytes might be generated or introduced.Clinical trials to test cardiomyocyte replacement (cardiomyogenesis), long a goal of SPC-based therapy, are bound to take place in the near future, thanks to many investigators who are developing technologies for efficient generation of cardiomyocytes from SPCs and for increasing their retention after transplantation.In weighing the benefits of replacement therapies, we should not overlook the fact that SPC-derived cardiomyocytes exhibit variable electrophysiological properties and are typically immature compared with adult cardiomyocytes (see below).This immaturity of primitive SPC-derived cardiomyocytes remains a major hurdle toward developing safe cell therapies.In anticipation of improved cardiomyogenesis in future cell therapies, we will review here developmental and electrophysiological challenges, common to all SPC-derived cardiomyocytes, that need to be resolved to improve the maturation of primitive SPC-derived cardiomyocytes and to avoid unwanted risks of increasing arrhythmic incidence (proarrhythmia) after transplantation.
HIF-1 regulates heritable variation and allele expression phenotypes of the macrophage immune response gene SLC11A1 from a Z-DNA–forming microsatellite
Authors: Henry K. Bayele, Carole Peyssonnaux, Alexandra Giatromanolaki, Wagner W. Arrais-Silva, Hiba S. Mohamed, Helen Collins, Selma Giorgio, Michael Koukourakis, Randall S. Johnson, Jenefer M. Blackwell, Victor Nizet, Surjit Kaila S. Srai
Journal: Blood (2007)
Selecting the Optimal Candidate for Adjuvant Radiotherapy After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis
Authors: Firas Abdollah, Nazareno Suardi, Cesare Cozzarini, Andrea Gallina, Umberto Capitanio, Marco Bianchi, Maxine Sun, Nicola Fossati, Niccolò Maria Passoni, Claudio Fiorino, Nadia Di Muzio, Pierre I. Karakiewicz, Patrizio Rigatti, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2012)
Ribcage hyperinflation occurrence during exercise in obese adolescents
Authors: Antonella LoMauro, Andrea Aliverti, Ambra Cesareo, Desy Salvadego, Bruno Grassi, Fiorenza Agosti, Alessandra Patrizi, Gabriella Tringali, Alessandro Sartorio
Journal: European Respiratory Journal (2014)

Breathing at low pulmonary volumes is one of the several respiratory factors that distinguish obesity and contribute to limit the ventilator constraint on exercise capacity in these patients.

In order to investigate if obese adolescents are characterized by a specific pattern of adaptation of their ventilator pump, 12 male patients (age: 16±1 [x±standard deviation] years, body mass index: 37±5 Kgcm-2) were evaluated during incremental exercise (increments of 20W/minute until the limit of tolerance) on a cycle ergometer. Total and compartmental chest wall volumes were measured by opto-electronic plethysmography during rest and exercise.

The progressive increase in tidal volume was achieved by a progressive increase of end-inspiratory chest wall volume while end-expiratory chest wall volume significantly decreased only at maximal workload.

End-expiratory abdominal and ribcage volumes showed an opposite behaviour. The former significantly decreased while the latter increased with time. End-inspiratory ribcage expansion augmented during exercise (figure 1).

Our results suggest that dynamic ribcage hyperinflation occurs in obese adolescent during incremental exercise. It seems that a ventilatory adaptation oriented toward higher ribcage operating volume is adopted to try to benefit from breathing at higher lung volumes and to exploit the exercise-induced lung volume recruitment where these patients maybe meet a better thoracic compliance.

![Figure][1]  [1]: pending:yes
SLAT regulates Th1 and Th2 inflammatory responses by controlling Ca2+/NFAT signaling
Authors: Stéphane Bécart, Céline Charvet, Ann J. Canonigo Balancio, Carl De Trez, Yoshihiko Tanaka, Wei Duan, Carl Ware, Michael Croft, Amnon Altman
Journal: Journal of Clinical Investigation (2007)

SWAP-70-like adapter of T cells (SLAT) is a novel guanine nucleotide exchange factor for Rho GTPases that is upregulated in Th2 cells, but whose physiological function is unclear. We show that SLAT(-/-) mice displayed a developmental defect at one of the earliest stages of thymocyte differentiation, the double-negative 1 (DN1) stage, leading to decreased peripheral T cell numbers. SLAT(-/-) peripheral CD4(+) T cells demonstrated impaired TCR/CD28-induced proliferation and IL-2 production, which was rescued by the addition of exogenous IL-2. Importantly, SLAT(-/-) mice were grossly impaired in their ability to mount not only Th2, but also Th1-mediated lung inflammatory responses, as evidenced by reduced airway neutrophilia and eosinophilia, respectively. Levels of Th1 and Th2 cytokine in the lungs were also markedly reduced, paralleling the reduction in pulmonary inflammation. This defect in mounting Th1/Th2 responses, which was also evident in vitro, was traced to a severe reduction in Ca(2+) mobilization from ER stores, which consequently led to defective TCR/CD28-induced translocation of nuclear factor of activated T cells 1/2 (NFATc1/2). Thus, SLAT is required for thymic DN1 cell expansion, T cell activation, and Th1 and Th2 inflammatory responses.
Impact of Respiratory Virus Infections on Persons With Chronic Underlying Conditions
Authors: W. Paul Glezen
Journal: JAMA (2000)

2][3] Despite the secular trend for decreasing hospitalization rates overall, the number and rate of hospitalizations for persons with acute lower respiratory tract infections increasedsteadilyduringthelast20years.Almost 1.5 million persons were hospitalized in 1995 after an average increase of more than 28 000 per year since 1980. 1 The hospitalization rate for persons 65 years of age or older with pneumonia increased by 50% from 1985 to 1995. 3 The rates of acute lower respiratory tract infections cited above do not include exacerbations of asthma or chronic obstructive pulmonary disease (COPD).During the same period, the death rate for women with COPD doubled and the hospitalizationrateforpoorblackchildrenwith asthma was 4 times greater than that for children from middle-income families.8][9] These studies showed that influenza virus and respiratory syncytial virus (RSV) were frequently associated with lower respiratory tract illnesses resulting in hospitalization.Recognizing that these conditions are preventableor potentially preventable-with existing technology, this study was designed to examine comprehensively within a defined population the role of respiratory virus infections in acute respiratory conditions leading to hospitalization of persons of all ages with chronic underlying conditions. METHODS Clinical and Epidemiologic MethodsFor a 4-year period, July 1991 through June 1995, patients from 4 large clinics were enrolled within 1 day of ad-mission to the hospital.The participating clinics were the Casa de Amigos and Martin Luther King Clinics of the Harris County Hospital District (HCHD) and the Pasadena and West Clinics of Kelsey-Seybold Clinics, all located in