tbuckley/cabot-search huggingface dataset:
Tissue-Engineered Myocardial Patch Derived From Extracellular Matrix Provides Regional Mechanical Function
Authors: Paul V. Kochupura, Evren U. Azeloglu, Damon J. Kelly, Sergey V. Doronin, Stephen F. Badylak, Irvin B. Krukenkamp, Ira S. Cohen, Glenn R. Gaudette
Journal: Circulation (2005)

Extracellular matrix (ECM), a tissue-engineered scaffold, recently demonstrated cardiomyocyte population after myocardial implantation. Surgical restoration of myocardium frequently uses Dacron as a myocardial patch. We hypothesized that an ECM-derived myocardial patch would provide a mechanical benefit not seen with Dacron.Using a canine model, a full thickness defect in the right ventricle was repaired with either Dacron or ECM. A third group had no surgery and determined baseline RV function. Eight weeks later, global systolic function was assessed by the preload recruitable stroke work relationship. Regional systolic function was measured by systolic area contraction (SAC), calculated by high density mechanical mapping. Tau was used to assess global diastolic function. Recoil rate and diastolic shear were used as measures of regional diastolic function. After functional data acquisition, tissue was fixed for histological evaluation. Global systolic and diastolic functions were similar at baseline and after ECM and Dacron implantation. Regional systolic function was greater in the ECM group compared with the Dacron group (SAC: 4.1+/-0.9% versus -1.8+/-1.1, P<0.05). Regional diastolic function was also greater in the ECM group (recoil rate (degrees sec(-1)): -44+/-7 versus -17+/-2, ECM versus Dacron; P<0.05). Immunohistochemical analysis revealed cardiomyocytes in the ECM implant region, a finding not seen with Dacron.At 8 weeks, an ECM-derived tissue-engineered myocardial patch provides regional mechanical function, likely related to cardiomyocyte population. These results are in sharp contrast to Dacron, a commonly used myocardial patch.
Fifty million people use computerised self triage
Authors: Jeremy C Wyatt
Journal: BMJ (2015)

A global opportunity, not a threat

Self help triage is not new,1 and most doctors have probably been tempted to use Google to check a patient’s symptoms.2 After reading the study of self help triage tools by Semigran and colleagues in this issue (doi:10.1136/bmj.h3480),3 some doctors may advise patients to use these tools when clinical support is hard to access—for example, while on a plane, holidaying abroad, or working on an oil rig. But few doctors would want politicians to see these tools as a cheaper and more accessible substitute for face to face out of hours services. So, what is the role of self help triage and how should we respond to the current findings?

In Semigran and colleagues’ study, the mean accuracy of self help triage tools was only 58%,3 but several arguments still favour self help over telephone or face to face triage. These tools have the potential to change the lives of people who are too shy or dysarthric to use telephone triage or too frail to access a walk-in centre. A study in 1976 showed that people are more honest about their alcohol intake to a computer than to a doctor,4 and in a 1992 trial, pregnant women shared more …
Accumulation of 3 H-Estradiol in Transplanted Interstitial Cell Tumors in Mice 2
Authors: w. E. Bollengier, A. J. Eisenfeld, W. U. Gardner
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Accumulation of 3H-Estradiol in Transplanted Interstitial Cell Tumors in Mice Get access w. E. Bollengier, w. E. Bollengier Departments of Anatomy and Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510 Search for other works by this author on: Oxford Academic PubMed Google Scholar A. J. Eisenfeld, A. J. Eisenfeld Departments of Anatomy and Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510 Search for other works by this author on: Oxford Academic PubMed Google Scholar W. U. Gardner W. U. Gardner Departments of Anatomy and Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 1, January 1973, Pages 195–200, https://doi.org/10.1093/jnci/50.1.195 Published: 01 January 1973 Article history Received: 07 July 1972 Accepted: 15 September 1972 Published: 01 January 1973
Serologically assessed elastin degradation is related to force vital capacity in patients with IPF
Authors: Jacob Hull Kristensen, Federica Genovese, Fernando Martinez, Cory Hogaboam, Han Meilan, Morten Asser Karlsdal, Diana Julie Leeming
Journal: European Respiratory Journal (2013)

Introduction: Elastin is a signature protein of the lungs and loss of elasticity is a pathological feature of a COPD and IPF. The pathogenesis involves an inflammatory response and tissue turnover mediated by proteases, especially matrix metalloprotease (MMP)-12, secreted by activated macrophages.  Aim: We developed an optimized assay for the assessment of elastin degradation mediated by MMP-9 and MMP-12. The objective was to investigate the ability to non-invasively provide information in relation to lung function during pulmonary disease.  Methods: Human insoluble lung elastin was in vitro cleaved for 2-169 hours by proteases and 400 fragments were identified by MS. A MMP-9 and -12 generated elastin neoepitope cleaved at the amino acid position 444 was chosen for monoclonal antibody generation for ELISA development. ELM was assessed in serum samples from a cohort of COPD (n=10), IPF (n=29) patients and healthy controls (n=11), stratified according to their forced vital capacity (FVC).  Results: ELM was specific towards MMP-12 degraded lung elastin. ELM was related to disease in IPF patients with significant increased levels in IPF (p  Discussion: We showed that this novel marker of MMP-12 degraded elastin was able to diagnose IPF and that the ELM marker was correlated to FVC in IPF patients. Even though these findings need to be validated in larger clinical settings, the ELM marker described showed potential as marker of progression in IPF patients.
Diaphragm postinspiratory inspiratory activity (PIIA) with sustained hypoxia
Authors: Michael Ji, Jenny Jagers, Paul Easton
Journal: European Respiratory Journal (2013)

Introduction: Each breath neurally has three phases: inspiration, postinspiration and expiration. However, postinspiration activity, i.e. expiratory breaking, may not be universal, and may be undesirable in some muscles. Little is known about postinspiratory activity (PIIA) during hypoxia.  Aim: Determine if postinspiratory activity occurs in costal (COS) and crural (CRU) diaphragm during sustained hypoxia in awake canines.  Methods: 28 days after implantation of sonomicrometry and EMG electrodes in COS and CRU, we measured awake airflow, SpO2, ETCO2, diaphragm EMG and shortening (SHORT) during room air breathing then 25 min isocapnic hypoxia (mean 79.7% SpO2). We report: 5 min room air (BASE), sustained hypoxia - first 2 min (PEAK) and final 5 min (PLATEAU).  Results: For N=8 (mean 28.9 kg), minute ventilation, tidal volume, EMG and SHORT of COS and CRU increased significantly from BASE to PEAK, then decreased to PLATEAU (p  Conclusion: Hypoxia elicits prominent diaphragm postinspiratory activity which does not resolve when hypoxia is sustained. This occurs even in COS which has minimal spindles or proprioceptive feedback for protection. This deviation of PIIA from normal diaphragm activity may be potentially injurious.
High-resolution computed tomography pattern reflects pathophysiologic difference in acute exacerbation of idiopathic interstitial pneumonia
Authors: Toru Arai, Yoshikazu Inoue, Kazunobu Tachibana, Chikatoshi Sugimoto, Tomoko Kagawa, Yasushi Inoue, Masanori Kitaichi, Tomohisa Okuma, Masanori Akira, Seiji Hayashi
Journal: European Respiratory Journal (2013)

Background:  Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) (AE-IPF) shows poor prognosis and high-resolution computed tomography (HRCT) pattern (diffuse pattern) is a significant prognostic factor in AE-IPF (Akira M, 2008 AJRCCM).   Aims:  We retrospectively compared clinical findings between AE-idiopathic interstitial pneumonias (IIPs) with diffuse pattern and non-diffuse pattern to clarify the difference in pathophysiology and clinical behaviors of the two patterns.   Subjects:  Seventy cases of AE-IIPs were diagnosed according to the guidelines of Japanese respiratory society in 2004 and classified with radiological and/or pathological findings into two groups: IPF (n=55) and non-IPF (n=15).   Methods:  Clinical findings were compared between two HRCT pattern (diffuse pattern and non-diffuse pattern). Prognostic significance of each clinical factor was evaluated by univariate and multivariate Cox proportional hazard analysis separately in diffuse and non-diffuse pattern.   Results:  In diffuse pattern, white blood cell and C-reactive protein was significantly higher and serum Krebs von den Lungen (KL)-6 and P/F ratio was significantly lower than those in non-diffuse pattern. Multivariate Cox proportional hazard regression analysis showed that lower immunoglobulin-G (IgG) and higher KL-6 is significant predictor of a bad prognosis in diffuse pattern. In non-diffuse pattern higher ratio of increase in KL-6 after the AE/KL-6 before AE is a good prognostic factor.   Conclusions:  Serum KL-6 has a different prognostic value between two radiological patterns in AE-IIPs. The pathophysiology of the two types of AE-IIPs might be different.
Outcomes from use of targeted therapy in pulmonary hypertension associated with sarcoidosis (PHAS)
Authors: John Cannon, Colm McCabe, Joanna Pepke-Zaba, Karen Sheares
Journal: European Respiratory Journal (2012)

Pulmonary hypertension is a recognised complication of sarcoidosis and may arise from several aetiological pathways. We report our experience of patients with PHAS-GroupV on targeted treatment.  Retrospective study of patient outcomes with PHAS. All patients underwent right heart catheterisation satisfying criteria for diagnosis of PAH. We reviewed 16 patients, 10 of whom died in mean f/u 32m. Patients dichotomised into 2 groups (responders and non-responders) based on improvement in log ntproBNP and 6MWD within 6 months of therapy initiation.  Treatment response was associated with a reduced risk of death. Cohort phenotypes suggest that treatment response may not be predicted from sarcoid stage, functional class, FVC or presence of extrapulmonary features. However elevation in PVR may possibly be associated with a favourable response. An RCT is indicated to evaluate a larger cohort.
Amelioration of human neutrophil elastase-induced emphysema in hamsters by pretreatment with an oligopeptide chloromethyl ketone
Authors: EC Lucey, PJ Stone, JC Powers, GL Snider
Journal: European Respiratory Journal (1989)

Human neutrophils are a likely source of elastase in the pathogenesis of human pulmonary emphysema. A study was undertaken to determine whether emphysema, induced in hamsters by intratracheal treatment with human neutrophil elastase (HNE), could be ameliorated by intratracheal instillation of succinyl-alanyl-alanyl-prolyl-valine-chloromethyl ketone (CMK). One mg of CMK was given to hamsters 1 h before 300 or 360 micrograms HNE or 1 h or 4 h after 360 micrograms HNE. The animals were studied eight weeks after treatment. The CMK given 4 h after HNE did not ameliorate the emphysema. The CMK given 1 h before HNE, ameliorated the development of emphysema but not bronchial secretory cell metaplasia. A molar ratio of instilled CMK to HNE of 128 was required for 50% in vivo effectiveness in ameliorating emphysema. Clearance studies indicated that 6.9% of the instilled CMK could be lavaged from the lungs 1 h after instillation. Therefore, an 8.9 to 1 molar ratio of lavageable CMK to HNE, at the time of HNE instillation, resulted in 50% protection. Using an in vitro assay with 3H-elastin as substrate, a 3 to 1 molar ratio of CMK to HNE was required to inhibit 50% of the elastolytic activity; 14% of the activity remained with an 18 to 1 molar ratio of CMK to HNE. Study of the in vivo effectiveness of anti-elastases, given as pretreatment in ameliorating HNE-induced emphysema and secretory cell metaplasia, is a reasonable bioassay, which may be used as a step in evaluating such agents for possible use in the prevention of human disease.
REINVENTING PUBLIC HEALTH
Authors: P. Lee, D. Paxman
Journal: Annual Review of Public Health (1997)

▪ Abstract This chapter is a review of the current state of public health in light of the social, political, economic, scientific, and technological changes buffeting the United States. As an assessment of progress in current public health efforts, we address the five major issues in public health for the 1990s raised by Breslow ( 8 ): reconstruction of public health; setting objectives for public health; from disease control to health promotion; determinants of health and health policy; continuing social inequities and their impacts on health; and the health implications of accelerating developments in technology. Finally, we look to the twenty-first century and provide five clear paths necessary to strengthen the capacity of public health agencies to protect and improve the health status of the population.
Clinical manifestations of selective IgA immunodeficiency in childhood
Authors: Borislav Kamenov, Svetlana Kamenov, Aleksanar Kamenov, Hristina Stamenkovic, Tatjana Stankovic
Journal: European Respiratory Journal (2013)

Introduction: Selective IgA deficiency is the most common primary immunodeficiency, with a prevalence of approximately 1/600.  Methods: The clinical manifestations of pediatric patients diagnosed as selective IgA immunodeficiency were analyzed, because of clinical heterogeneity in this category of patients.  Results: 84 patients with selective IgA immunodeficiency were analyzed with the following clinical manifestations: asymptomatic (13); patients who suffer from frequent respiratory and gastrointestinal infections (28), patients with vitiligo (9), autoimmune hypothyroidism (5), cow milk intolerance (10), allergy (7) rheumatoid arthritis (5), coeliac disease (7). Children with recurrent respiratory infections usually had a defect in antibody responses toward polysaccharides, associated with IgG2 (3) or IgG4 (5) deficiency. It seams that infection susceptibility was not related to the degree of IgA deficiency, but to deficiency of IgG4 and IgG2, as well as to low basal serum concentrations of anti-polysaccharide antibodies. One IgA-deficient patients develop more severe common variable immunodeficiency, which is associated with decreased IgG and IgM production as well as partial T-cell defect. Some children developed serous infections during the follow up. Hyper IgG was observed in the most of the patients with selective IgA immunodeficiency (69) as a compensatory phenomenon or because of disregulation of the oral tolerance in those patients. Increased IgE did not differ from the control group.  Conclusion: Children with selective IgA immunodeficiency have high risk of serious infections, inflammatory, autoimmune or other chronic diseases.
Production and Release of Virus-Like Particles by Cultures of Agent-Free Ascites Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: George Miroff, Dorothy G. Feldman
Journal: JNCI Journal of the National Cancer Institute (1963)

Virus-like particles in milk and breast tissue of agent-bearing mice but not in animals free from the agent suggest a causal relationship between these particles and mammary tumor development. The validity of this relationship was tested by use of a culture of mammary gland ascites tumor freed from the mammary tumor agent, as demonstrated with bioassay, by passage in agent-free mice for many years. These cells, propagated intraperitoneally in infected and agent-free hosts and examined with the electron microscope, failed to produce type A or B particles. When propagated subcutaneously for periods up to 31 days, type A particles were found in the cells irrespective of whether the host possessed the agent. Production of virus-like particles by monolayer cultures of these cells, when brought in contact with milk preparations containing or devoid of mammary tumor agent, or with buffer alone, was compared with the ability of respective culture fluids to produce mammary tumors when injected into susceptible agent-free female mice. The presence or absence of A and/or B particles from these cultures could not be correlated with the tumor-producing potential of the material under test. Material injected for assay contained many B particles. If the B particles are the agent, then the number injected should have resulted in a positive bioassay. Failure to obtain a positive bioassay from the tissue culture fluids in contact with cells propagated in vitro that are producing these particles, morphologically indistinguishable from those developing in vivo, may indicate: 1) Their synthesis from components in the media ordinarily foreign to the host imparts sufficient antigenicity to the particles to render them incapable of initiating the oncogenic process, or 2) these particles are a cellular product proliferated as a result of infection by the mammary tumor agent.
Inflammatory Breast Cancer: The Experience of the Surveillance, Epidemiology, and End Results (SEER) Program
Authors: P H Levine, S C Steinhorn, L G Ries, J L Aron
Journal: JNCI Journal of the National Cancer Institute (1985)

Journal Article Inflammatory Breast Cancer: The Experience of the Surveillance, Epidemiology, and End Results (SEER) Program Get access Paul H. Levine, Paul H. Levine 3 3Address reprint requests to Dr. Levine, Landow Bldg., Rm. 8C41, National Institutes of Health, Bethesda, MD 20205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Sandra C. Steinhorn, Sandra C. Steinhorn Search for other works by this author on: Oxford Academic PubMed Google Scholar Lynn Gloeckler Ries, Lynn Gloeckler Ries Search for other works by this author on: Oxford Academic PubMed Google Scholar Joan L. Aron Joan L. Aron Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 74, Issue 2, February 1985, Pages 291–297, https://doi.org/10.1093/jnci/74.2.291 Published: 01 February 1985 Article history Received: 05 March 1984 Accepted: 23 August 1984 Published: 01 February 1985
KLF6 orchestrates cardiac myocyte-to-fibroblast communication: ‘He who has ears to hear, let him hear’: Figure 1
Authors: Jean-Luc Balligand
Journal: Cardiovascular Research (2015)

As in many organs, cardiac fibrosis is a devastating consequence of chronic stress,1 be it haemodynamic or through prolonged exposure to neurohormones, most notably angiotensin II (Ang II).2 It involves a complex interplay between parenchymal, vascular, and interstitial (fibroblastic and inflammatory) cells communicating through, and regulated by, paracrine signalling and matricellular proteins.3 In such intricated process, specificity of signalling is key, and regulation of cell–cell crosstalk through Kruppel-like factors (KLFs) is no exception.

KLFs belong to a family of 18 members of zinc-finger DNA-binding transcription factors with large cellular distribution and pleiotropic roles in cellular biology.4 KLF4, 5, 10, and 15 have previously been implicated in cardiac muscle differentiation or remodelling.5 Their effect varies between different isoforms, and for the same isoform, it is dependent on a specific cellular context, as commonly seen for other families of transcription factors. In the process of fibrosis in the liver, particularly, reduced expression of KLF6 in hepatic stellate cells amplifies the fibrotic process following acute or chronic liver injury.6 Reduction of the same KLF6 in cardiac myocytes produces exactly the opposite during Ang II-induced myocardial fibrosis, as illustrated in the paper …
The tenth year preliminary results of smoking cessation policlinics of Karadeniz Technical University medicine faculty
Authors: Funda Oztuna, Gamze Çan, Sibel Ayik, Tevfik Özlü, Ismail Yilmaz
Journal: European Respiratory Journal (2011)

Aim:  Our outpatient smoking cessation clinic was opened in April 2000. Aim of this study was to create a database for our national long-term smoking cessation rates and to share our experience.   Method:  We included 696 patients who had applied our smoking cessation clinic between April 2000- December 2010 years. After smoking habits and sociodemographic features of the people were asked, all the people attended to a suitable smoking cessation program. The results were analyzed by Chi-square test, Kaplan Meier survival analysis and Cox-regression analysis.   Results:  It was observed that 696 people containing 408 (58.6%) men and 282 (40.5%) women visited the polyclinic during this period. According to duration without smoking, women did not smoke 24.36±5.83 months and men did not smoke 21.63±4.66 months. Success rates were not different between men and women (Log Rank p=0.729) at the end of tenth years. The success rates at the end of the first, the fifth and tenth years in patients who attended smoking cessation programme were 58%, 40.6% and 31.7% respectively. We found that male gender, lack of regular income, low education level and the amount of cigarettes smoked per day were independent risk factors for restart smoking by Cox-regression analysis.   Discussion:  In coclusion, our smoking cessation rates have decreased over the years. Especially, male gender, low educational level, lack of regular income and high amounts of daily cigarette were reduced success rates. We think that more close follow- up of these patients might positively affect on the success rates.
Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.
Authors: A N Serafini, S J Houston, I Resche, D P Quick, F M Grund, P J Ell, A Bertrand, F R Ahmann, E Orihuela, R H Reid, R A Lerski, B D Collier, J H McKillop, G L Purnell, A P Pecking, F D Thomas, K A Harrison
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.