tbuckley/cabot-search huggingface dataset:
Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlled study.
Authors: D Olivieri, A Chetta, M Del Donno, G Bertorelli, A Casalini, A Pesci, R Testi, A Foresi
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

In a double-blind, parallel-group study, we examined the effect of short-term treatment with inhaled fluticasone propionate (FP) in a group of 20 nonsmoking asthmatic patients who required only beta2-agonists to control their symptoms. We administered FP (250 microg twice daily) or matched placebo for 6 wk. Methacholine challenge was performed before treatment, after 3 wk, and at the end of treatment. Each patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy before and after treatment. Eight patients in the placebo group and nine patients in the FP group completed the study. Bronchial responsiveness to methacholine decreased significantly only after 6 wk of treatment with FP (p < 0.05). When we compared the FP group with the placebo group, we observed a significant decrease only in the number of cells expressing intracellular adhesion molecule-1 (ICAM-1) and MAC-1 (p < 0.04 and p < 0.03, respectively). Moreover, we saw that the tryptase level in BAL decreased (p < 0.001), whereas the eosinophil cationic protein (ECP) level did not change significantly. Additionally, the number of eosinophils and mast cells in the lamina propria in bronchial biopsies specimens was significantly smaller in the FP group than in the placebo group (p < 0.02 and p < 0.01, respectively). Additionally, in the FP group, we found that basement-membrane thickness was significantly decreased when compared with that of the placebo group (p < 0.05). In conclusion, our results show that short-term treatment with low-dose FP reduces inflammatory cell infiltration into the lamina propria in bronchial biopsy specimens. Moreover, short-term low-dose FP treatment might control the intensity of airway remodeling in mild asthma.
Psychosocial risks for low back pain: are these related to work?
Authors: A. C Papageorgiou, P. R Croft, E. Thomas, A. J Silman, G. J Macfarlane
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVES</h3> To examine whether psychosocial risks for low back pain, reported in previous studies, are specific to the working population or are more widely relevant. <h3>METHODS</h3> A large population-based survey identified subjects free of low back pain, and obtained information on the degree of satisfaction with work (or not working) and the adequacy of income for their family's needs. New episodes of consulting and non-consulting low back pain were identified prospectively over 12 months. The psychosocial risks for developing a new low back pain episode are examined in employed and non-employed groups separately. <h3>RESULTS</h3> Dissatisfaction with work status doubled the risk of reporting a new low back pain episode in both the employed (odds ratio 2.0, 95% confidence intervals 1.2, 3.3) and non-employed (OR 2.0, 1.2, 3.1). Those perceiving their income as inadequate were at a threefold risk of consulting for this symptom regardless of their employment status (employed: OR 3.6, 1.8, 7.2; non-employed: OR 3.6, 1.4, 9.0). <h3>CONCLUSION</h3> Psychosocial factors pose similar risks for a new low back pain episode in workers and the non-employed. This suggests that such influences may not be related solely to work but be a function of general aspects of life. The economic and individual impact of psychosocial interventions in the workplace, therefore, are likely to be limited unless account is taken of the influence of broader non-work related aspects.
Estrogen Receptor Polymorphism at Codon 325 and Risk of Breast Cancer in Women Before Age Forty
Authors: Melissa C. Southey, Leigh E. Batten, Margaret R. E. McCredie, Graham G. Giles, Deon J. Venter, Gillian Dite, John L. Hopper
Journal: JNCI Journal of the National Cancer Institute (1998)

The estrogen receptor (ER) protein is believed to play a role in the development and progression of breast cancer. In a previously published U.S. clinic-based study, a polymorphism in the ER gene (codon 325, CCC --> CCG) was found to be more common in 34 case subjects with a family history of breast cancer than in 154 case subjects without such a history (mean allele frequencies +/- standard error = 0.28+/-0.05 versus 0.11+/-0.02; P<.001). To determine whether this polymorphism is a risk factor for early-onset breast cancer, we conducted a population-based, case-control-family study in Australia.Case subjects under the age of 40 years with a first primary breast cancer and control subjects, frequency-matched to the case subjects on the basis of age, and their relatives were interviewed to assess the family history of breast cancer. Polymorphism status of the ER gene was determined for 388 case subjects and 294 control subjects. All statistical tests were two-tailed.There was no association between ER gene polymorphism status and breast cancer, before or after adjustment for risk factors. There was no difference in allele frequencies between case subjects and control subjects (0.232+/-0.015 versus 0.209+/-0.017; P = .4) or between women with and without a family history of breast cancer (P = .3), irrespective of case-control status. The findings were not altered when different definitions of family history of breast cancer were used and when allele frequencies were adjusted for residence and country of birth.We found no evidence that the ER codon 325 polymorphism is associated with breast cancer before the age of 40 years or with a family history of breast cancer, despite ample power to detect effects half the magnitude of those previously reported.
Recombinant Adeno-Associated Virus Serotype 9 Leads to Preferential Cardiac Transduction In Vivo
Authors: Christina A. Pacak, Cathryn S. Mah, Bijoy D. Thattaliyath, Thomas J. Conlon, Melissa A. Lewis, Denise E. Cloutier, Irene Zolotukhin, Alice F. Tarantal, Barry J. Byrne
Journal: Circulation Research (2006)

Heart disease is often the end result of inherited genetic defects, which may potentially be treatable using a gene-transfer approach. Recombinant adeno-associated virus (rAAV)-mediated gene delivery has emerged as a realistic method for the treatment of such disorders. Here, we demonstrate and compare the natural affinity of specific AAV serotype capsids for transduction of cardiac tissue. We compared the previously accepted optimal rAAV serotype for transduction of skeletal muscle, rAAV2/1, with rAAV2/8 and the newer rAAV2/9 vectors carrying the CMV-lacZ construct in their respective abilities to transcend vasculature and transduce myocardium following intravenous delivery of 1x10(11) vector genomes in neonatal mice. We found that both rAAV2/8 and rAAV2/9 are able to transduce myocardium at approximately 20- and 200-fold (respectively) higher levels than rAAV2/1. Biodistribution analysis revealed that rAAV2/9 and rAAV2/8 demonstrate similar behavior in extracardiac tissue. Vector genome quantification showed an increase in genome copy numbers in cardiac tissue for several weeks following administration, which corresponds to expression data. In addition, we intravenously administered 1x10(11) vector genomes of rAAV2/9-CMV-lacZ into adult mice and achieved an expression biodistribution profile similar to that found following delivery to newborns. Although higher doses of virus will be necessary to approach those levels observed following neonatal injections, adult myocardium is also readily transduced by rAAV2/9. Finally, we have demonstrated physiological disease correction by AAV9 gene transfer in a mouse model of Pompe disease via ECG tracings and that intravenous delivery of the same vector preferentially transduces cardiac tissue in nonhuman primates.
The Evolution of the Physician's Role
Authors: Eric P. Wilkinson
Journal: JAMA (2001)

CONTROVERSY CONTINUES OVER HOW PHYSICIANS SHOULD BE employed in the United States. Some workforce experts believe there is a physician oversupply, arguing that allopathic, osteopathic, and international medical graduates are all competing for limited practice opportunities in the managed care setting. Other experts have advocated the expansion of US medical school positions, claiming that physician demand has not lessened despite a perceived oversupply. Yet others continue to hold that a “maldistribution” of physicians into urban and suburban areas, rather than rural and inner-city regions, is the root of the problem. Recent data suggest that this practice disparity, the target of primary care initiatives in many medical schools, has not closed, and may even have widened. Whatever the outcome of the physician workforce debate, physicians will face a changing landscape of clinical practice roles as well as increased availability of alternate career options. Some medical graduates are choosing to reject traditional clinical roles altogether. In this issue, we explore the continuing evolution of physicians’ clinical and nonclinical roles, including additional career possibilities. The Association of American Medical Colleges has monitored medical students’ future practice patterns since 1978, polling medical students each year prior to graduation to ask them about their career plans. In this issue, Dr Richard and colleagues examine 10 years of data from the questionnaire relevant to medical student career decisions, especially those outside traditional clinical medicine. Physicians seeking an alternative path have frequently sought additional graduate or professional degrees to expand their career options. Many medical schools have responded to the demand by offering combined degree programs, traditionally in public health and health policy, and, more recently, in business and law. The juris doctor degree is one possibility that has grown in popularity in the past decade: in this issue, Matthew Howard, MD, JD, outlines the development of legal medicine and the roles that physicians with legal training can play. In this era of managed care, training in business may be an asset. Not only are some physicians seeking business knowledge to increase their proficiency in the financial affairs of medicine, but businesses are also seeking persons with MD and combined MD/PhD degrees to bring new knowledge to the workplace. Michael Ennen examines why firms are hiring physicians as consultants. What possible choices exist for medical students who decide to contribute, outside of traditional research, to the advancement of medical science? For those with patience, medical editing is a possibility. The effort that brings you JAMA and MSJAMA—long hours of editing, reediting, and copyediting—is explored by Jerome Kassirer, MD, a former editor-in-chief of the New England Journal of Medicine.
Effects of PEEP on inspiratory resistance in mechanically ventilated COPD patients
Authors: C. Guérin, G. Fournier, J. Milic-Emili
Journal: European Respiratory Journal (2001)

This study aimed to investigate the effect of increased lung volume with positive end-expiratory pressure (PEEP) on respiratory resistance in patients with chronic obstructive pulmonary disease (COPD). Ten patients with COPD were mechanically ventilated for acute respiratory failure. PEEP was set at 0, 5, 10 and 15 cmH 2 O. Using the rapid airway occlusion technique, the total inspiratory resistance of the respiratory system was partitioned into interrupter ( R int,rs ) and additional effective (Δ R rs ) resistances. At each level of PEEP, at constant inflation flow, the inflation volume (Δ V ) was varied from 0.2–1 L, and, at constant Δ V , the inflation flow was varied from 0.2–1.2 L·s −1 . The changes in end-expiratory lung volume (ΔEELV) induced by PEEP were also measured. The difference between the EELV and the relaxation volume of the respiratory system (ΔFRC) increased significantly with PEEP of 10 and 15 cmH 2 O as compared to a PEEP of 0, the increase being associated with a significant reduction of R int,rs . By contrast, Δ R rs was independent of ΔFRC. At constant Δ V , R int,rs fitted Rohrer's equation ( R int,rs =K 1 +K 2 ×flow). While K 2 significantly declined with ΔFRC, K 1 did not change. At all levels of PEEP, Δ R rs was not influenced by ΔFRC. With increasing lung volume induced by positive end-expiratory pressure, the inspiratory airway resistance decreased, whereas the viscoelastic behaviour of the respiratory system, as reflected by additional effective resistance, did not change.
Plasma levels and effects of salbutamol after inhaled or i.v. administration in stable asthma
Authors: C Janson
Journal: European Respiratory Journal (1991)

The response and plasma levels of inhaled (0.15 mg.kg-1) and intravenous salbutamol (5 micrograms.kg-1) were studied in 12 patients who had previously been included in a study of acute severe asthma and were now in a stable phase. The maximal value for change (delta) in plasma salbutamol compared with the pretreatment value was higher after i.v. than after inhalation treatment (59 vs 30 nmol.l-1) but the areas under the curve (AUC) during 90 mins after treatment were similar for the two administration routes. The inter-individual differences in peak plasma salbutamol and AUC for delta plasma salbutamol were much greater after inhalation than after i.v. infusion. Immediately after treatment there was a greater increase in pulse rate (mean +17 vs +6 beats.min) and lower serum potassium level (mean -0.3 mmol.l-1) after i.v. than after inhalation treatment. The increase in peak expiratory flow (PEF) measured 90 min after the start of treatment (85 vs 31 l.min-1) and as AUC was significantly higher after inhalation than after i.v. treatment. Six patients had received i.v. treatment in the acute asthma study: in these patients delta PEF immediately after i.v. treatment was significantly lower in the stable situation (+49 vs +115 l.min-1). There was also a significant difference in the effect on the pulse rate immediately after i.v. treatment, with a decrease in the acute asthma and an increase in the stable asthma situation (-5 vs +16 beats.min-1).
Phenotypic plasticity of T cell progenitors upon exposure to Notch ligands
Authors: Andreas Krueger, Annette I. Garbe, Harald von Boehmer
Journal: The Journal of Experimental Medicine (2006)

Despite many efforts, the nature of thymic immigrants that give rise to T cells has remained obscure, especially since it became known that extrathymic lineage-negative, Sca-1–positive, c-kit high progenitor cells differ from intrathymic early T cell progenitors (ETPs) by functional potential and dependence on Notch signaling. After our observation that intrathymic T cell precursors expressing a human CD25 reporter under control of pre-TCRα regulatory elements almost exclusively have the ETP phenotype, we have analyzed the phenotypic changes of reporter-expressing common lymphoid progenitor (CLP) cells in the bone marrow when cultured on Delta-like 1–expressing stromal cells. We note that these quickly adopt the phenotype of double negative (DN)2 thymocytes with little display of the ETP phenotype. Our data suggest that common lymphoid progenitor (CLP) cells could be responsible for the rapid reconstitution of thymus function after bone marrow transplantation since CLP cells in the blood have the capacity to rapidly enter the thymus and become DN2 thymocytes.
Leukemia Inhibitory Factor Enhances Survival of Cardiomyocytes and Induces Regeneration of Myocardium After Myocardial Infarction
Authors: Yunzeng Zou, Hiroyuki Takano, Miho Mizukami, Hiroshi Akazawa, Yingjie Qin, Haruhiro Toko, Masaya Sakamoto, Tohru Minamino, Toshio Nagai, Issei Komuro
Journal: Circulation (2003)

Background— Myocardial infarction (MI) is a leading cause of cardiac morbidity and mortality in many countries; however, the treatment of MI is still limited. Methods and Results— We demonstrate a novel gene therapy for MI using leukemia inhibitory factor (LIF) cDNA. We injected LIF plasmid DNA into the thigh muscle of mice immediately after inducing MI. Intramuscular injection of LIF cDNA resulted in a marked increase in circulating LIF protein concentrations. Two weeks later, left ventricular remodeling, such as infarct extent and myocardial fibrosis, was markedly attenuated in the LIF cDNA–injected mice compared with vehicle-injected mice. More myocardium was preserved and cardiac function was better in the LIF-treated mice than in the vehicle-injected mice. Injection of LIF cDNA not only prevented the death of cardiomyocytes in the ischemic area but also induced neovascularization in the myocardium. Furthermore, LIF cDNA injection increased the number of cardiomyocytes in cell cycle and enhanced mobilization of bone marrow cells to the heart and their differentiation into cardiomyocytes. Conclusions— The intramuscular injection of LIF cDNA may induce regeneration of myocardium and provide a novel treatment for MI.
Pulmonary blastoma: a report of two cases and a review of the literature.
Authors: A Kennedy, A L Prior
Journal: Thorax (1976)

Pulmonary blastoma is the rarest malignant tumour of the lung. Two more cases are reported and the literature is reviewed. The first case, a woman, is the longest recorded survivor. An examination of all the reported cases shows that the tumour is less common and less agressive in women.
Continuous Glucose Monitoring
Authors: David C. Klonoff
Journal: Diabetes Care (2005)

Continuous glucose monitoring provides maximal information about shifting blood glucose levels throughout the day and facilitates the making of optimal treatment decisions for the diabetic patient. This report discusses continuous glucose monitoring in terms of its purposes, technologies, target populations, accuracy, clinical indications, outcomes, and problems. In this context, the medical literature on continuous glucose monitoring available through the end of 2004 is reviewed.

Continuous glucose monitoring provides information about the direction, magnitude, duration, frequency, and causes of fluctuations in blood glucose levels. Compared with conventional intensified glucose monitoring, defined as three to four blood glucose measurements per day, continuous monitoring provides much greater insight into glucose levels throughout the day. Continuous glucose readings that supply trend information can help identify and prevent unwanted periods of hypo- and hyperglycemia.

The difference between an intermittent and a continuous monitor for monitoring blood glucose is similar to that between a regular camera and a continuous security camera for monitoring an important situation. A regular camera takes discrete, accurate snapshots; its pictures do not predict the future; it produces a small set of pictures that can all be carefully studied; and effort is required to take each picture. A continuous security camera, on the other hand, takes multiple, poorly focused frames; displays a sequential array of frames whose trend predicts the future; produces too much information for each frame to be studied carefully; and operates automatically after it is turned on. The two types of blood glucose monitors differ in much the same way: 1 ) an intermittent blood glucose monitor measures discrete glucose levels extremely accurately, whereas a continuous monitor provides multiple glucose levels of fair accuracy; 2 ) with an intermittent monitor, current blood glucose levels do not predict future glucose levels, but with a continuous monitor, trends in glucose levels do have …
Targeting Protein Synthesis in a Myc/mTOR-Driven Model of Anorexia-Cachexia Syndrome Delays Its Onset and Prolongs Survival
Authors: Francis Robert, John R. Mills, Aouod Agenor, Dantong Wang, Sergio DiMarco, Regina Cencic, Michel L. Tremblay, Imed Eddine Gallouzi, Siegfried Hekimi, Simon S. Wing, Jerry Pelletier
Journal: Cancer Research (2011)

Anorexia-cachexia syndrome (ACS) is a major determinant of cancer-related death that causes progressive body weight loss due to depletion of skeletal muscle mass and body fat. Here, we report the development of a novel preclinical murine model of ACS in which lymphomas harbor elevated Myc and activated mTOR signaling. The ACS phenotype in this model correlated with deregulated expression of a number of cytokines, including elevated levels of interleukin-10 which was under the direct translational control of mTOR. Notably, pharmacologic intervention to impair protein synthesis restored cytokine production to near-normal levels, delayed ACS progression, and extended host survival. Together, our findings suggest a new paradigm to treat ACS by strategies which target protein synthesis to block the production of procachexic factors.
Intracoronary Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction
Authors: Volker Schächinger, Sandra Erbs, Albrecht Elsässer, Werner Haberbosch, Rainer Hambrecht, Hans Hölschermann, Jiangtao Yu, Roberto Corti, Detlef G. Mathey, Christian W. Hamm, Tim Süselbeck, Birgit Assmus, Torsten Tonn, Stefanie Dimmeler, Andreas M. Zeiher
Journal: New England Journal of Medicine (2006)

Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction.
mTOR signaling is activated by FLT3 kinase and promotes survival of FLT3- mutated acute myeloid leukemia cells
Authors: Weina Chen, Elias Drakos, Ioannis Grammatikakis, Ellen J Schlette, Jiang Li, Vasiliki Leventaki, Efi Staikou-Drakopoulou, Efstratios Patsouris, Panayiotis Panayiotidis, L Jeffrey Medeiros, George Z Rassidakis
Journal: Molecular Cancer (2010)

Abstract Activating mutations of the FLT3 gene mediate leukemogenesis, at least in part, through activation of PI3K/AKT. The mammalian target of rapamycin (mTOR)-Raptor signaling pathway is known to act downstream of AKT. Here we show that the mTOR effectors, 4EBP1, p70S6K and rpS6, are highly activated in cultured and primary FLT3 -mutated acute myeloid leukemia (AML) cells. Introduction of FLT3-ITD expressing constitutively activated FLT3 kinase further activates mTOR and its downstream effectors in BaF3 cells. We also found that mTOR signaling contributes to tumor cell survival, as demonstrated by pharmacologic inhibition of PI3K/AKT/mTOR, or total silencing of the mTOR gene. Furthermore, inhibition of FLT3 kinase results in downregulation of mTOR signaling associated with decreased survival of FLT3 -mutated AML cells. These findings suggest that mTOR signaling operates downstream of activated FLT3 kinase thus contributing to tumor cell survival, and may represent a promising therapeutic target for AML patients with mutated- FLT3 .