tbuckley/cabot-search huggingface dataset:
Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma
Authors: Michael B. Maris, Brenda M. Sandmaier, Barry E. Storer, Thomas Chauncey, Monic Jain Stuart, Richard T. Maziarz, Edward Agura, Amelia A. Langston, Michael Pulsipher, Rainer Storb, David G. Maloney
Journal: Blood (2004)
Effects of captopril administration on pulmonary haemodynamics and tissue oxygenation during exercise in ACE gene subtypes in patients with COPD: a preliminary study
Authors: H Kanazawa
Journal: Thorax (2003)

We have previously shown that angiotensin converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance of tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). A pilot study was designed to examine the effects of captopril on these exercise related variables in COPD patients categorised according to ACE gene polymorphisms.Thirty six patients with COPD (II=13, ID=11, DD=12) received oral captopril (25 mg) or placebo in a randomised, double blind, crossover manner and underwent right heart catheterisation with exercise.Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and lactate concentration after exercise with both placebo and captopril were higher in patients with the DD genotype than in those with the II or ID genotypes. In contrast, mixed venous oxygen tension (PvO(2)) was lower in patients with the DD genotype than in those with the other genotypes. Moreover, mPAP, PVR, and lactate concentration after exercise were lower in the captopril group than in the placebo group in patients with the II or ID genotype, but not in those with the DD genotype. PvO(2) after exercise was higher with captopril than with placebo in patients with the II genotype, but not in those with the other genotypes.These findings suggest that pulmonary haemodynamic variables and state of tissue oxygenation during exercise are dependent on ACE genotypes, and that captopril administration effectively influences these exercise related variables. Although the sample size in this pilot study was limited, it is likely that the improvement in exercise related variables in COPD patients with the II genotype is relatively sensitive to captopril.
Facial cooling, but not nasal breathing of cold air, induces bronchoconstriction: a study in asthmatic and healthy subjects
Authors: H Koskela, H Tukiainen
Journal: European Respiratory Journal (1995)

Reflex-mediated bronchoconstriction in cold climates may be more important than it has previously been thought. This issue has seldom been studied using physiological methods. We wanted to investigate, using physiological methods, what triggers the bronchoconstriction occurring at cold ambient temperature during resting nasal ventilation: cooling of the skin of the face or cooling of the nasal cavity. Three experiments were carried out in 15 stable asthmatics and 10 healthy volunteers: 1) a whole-body exposure to subfreezing temperature in an environmental chamber, during which the subjects breathed cold air through the nose; 2) a similar exposure to subfreezing temperature except that the subjects now breathed warm air through the mouth from outside the chamber; and 3) nasal breathing of subfreezing air from a heat exchanger whilst the subjects sat at room temperature. Spirometric values and facial skin temperature were measured both during and after the exposures. Maximal decrements (means +/- standard errors) of forced expiratory volume in one second (FEV1) in experiments 1, 2 and 3 were: 5.8 +/- 0.8, 5.1 +/- 0.7 and 2.1 +/- 0.5%, respectively (p &lt; 0.001). Only the two experiments in the environmental chamber induced significant bronchoconstriction. All responses were of similar magnitude in the asthmatic and the healthy subjects. The cooling of the skin of the face seems to be the trigger for the bronchoconstriction during resting nasal ventilation at cold ambient temperature both in asthmatic and nonasthmatic subjects.
PARTIAL INTESTINAL OBSTRUCTION IN A CHILD DUE TO POST-RECTAL TERATOMA
Authors: A. E. Sawday
Journal: BMJ (1925)

An infant may be left -with a weak digestion and fall into a state of marasmus.Bronchitis is a very common accompaniment, and such patients must always be kept very warm.After prolonged enteritis, swelling of the backs of the lhands anid dorsum of the feet is common.This is toxic oedema, anId hias niothing to do with kidney disease.Drugs form a minor part of the treatment.Bismuth in some form does, howeveir, lhelp to diminish the
The incidence of malignant disease in patients receiving cytotoxic therapy for rheumatoid arthritis.
Authors: A B Kirsner, S J Farber, R P Sheon, R I Finkel
Journal: Annals of the Rheumatic Diseases (1982)

One hundred and twenty-six patients with definite or classical rheumatoid arthritis admitted to hospital between 1965 and 1974 for cytotoxic therapy were studied for the presence and type of malignant disease. Each of the cytotoxic treated patients was age and sex matched to a rheumatoid arthritis patient admitted to hospital during the same years but who did not receive cytotoxic therapy. There was no increase in malignancy in the cytotoxic treated group over the control group.
Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, With Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients With Bladder Cancer
Authors: Hans von der Maase, Lisa Sengelov, James T. Roberts, Sergio Ricci, Luigi Dogliotti, T. Oliver, Malcolm J. Moore, Annamaria Zimmermann, Michael Arning
Journal: Journal of Clinical Oncology (2005)

Purpose To compare long-term survival in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium treated with gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). Patients and Methods Efficacy data from a large randomized phase III study of GC versus MVAC were updated. Time-to-event analyses were performed on the observed distributions of overall and progression-free survival. Results A total of 405 patients were randomly assigned: 203 to the GC arm and 202 to the MVAC arm. At the time of analysis, 347 patients had died (GC arm, 176 patients; MVAC arm, 171 patients). Overall survival was similar in both arms (hazard ratio [HR], 1.09; 95% CI, 0.88 to 1.34; P = .66) with a median survival of 14.0 months for GC and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (P = .53). The median progression-free survival was 7.7 months for GC and 8.3 months for MVAC, with an HR of 1.09. The 5-year progression-free survival rates were 9.8% and 11.3%, respectively (P = .63). Significant prognostic factors favoring overall survival included performance score (&gt; 70), TNM staging (M0 v M1), low/normal alkaline phosphatase level, number of disease sites (≤ three), and the absence of visceral metastases. By adjusting for these prognostic factors, the HR was 0.99 for overall survival and 1.01 for progression-free survival. The 5-year overall survival rates for patients with and without visceral metastases were 6.8% and 20.9%, respectively. Conclusion Long-term overall and progression-free survival after treatment with GC or MVAC are similar. These results strengthen the role of GC as a standard of care in patients with locally advanced or metastatic TCC.
The <i>Bordetella pertussis</i> adenylate cyclase toxin binds to T cells via LFA-1 and induces its disengagement from the immune synapse
Authors: Silvia Rossi Paccani, Francesca Finetti, Marilyne Davi, Laura Patrussi, Mario M. D'Elios, Daniel Ladant, Cosima T. Baldari
Journal: The Journal of Experimental Medicine (2011)

The Bordetella pertussis adenylate cyclase toxin (CyaA) assists infection by potently suppressing the host immune response. Although CyaA effectively targets T lymphocytes, its putative receptor on these cells is unknown. Here, we show that CyaA binds to T cells via the β2 integrin LFA-1 in its active conformation. CyaA clusters with LFA-1 at the immune synapse (IS), from which it induces the premature disengagement of LFA-1 concomitant with the dissipation of talin, which tethers the integrin to the underlying actin cytoskeleton. The CyaA-induced redistribution of LFA-1 was cAMP- and protein kinase A (PKA)–dependent. These results not only identify LFA-1 as a CyaA receptor on T cells but unveil a novel mechanism of immunosuppression whereby the toxin parasitizes its interaction with LFA-1 to inhibit signaling at the IS through the local production of cAMP. The data also provide novel insights into the role of cAMP/PKA signaling in controlling the dynamics of the IS.
A Mouse Model of Melanoma Driven by Oncogenic KRAS
Authors: Carla Milagre, Nathalie Dhomen, Felipe C. Geyer, Robert Hayward, Maryou Lambros, Jorge S. Reis-Filho, Richard Marais
Journal: Cancer Research (2010)

The small G-protein NRAS is mutated in 22% of human melanomas, whereas the related proteins KRAS and HRAS are mutated in only 2% and 1% of melanomas, respectively. We have developed a mouse model of melanoma in which Cre recombinase/LoxP technology is used to drive inducible expression of (G12V)KRAS in the melanocytic lineage. The mice develop skin hyperpigmentation, nevi, and tumors that bear many of the cardinal histopathology features and molecular characteristics of human melanoma. These tumors invade and destroy the underlying muscles and cells derived from them can grow as subcutaneous tumors and colonize the lungs of nude mice. These data establish that oncogenic KRAS can be a founder event in melanomagenesis.
Case fatality of COPD exacerbations: a meta-analysis and statistical modelling approach
Authors: M. Hoogendoorn, R. T. Hoogenveen, M. P. Rutten-van Molken, J. Vestbo, T. L. Feenstra
Journal: European Respiratory Journal (2010)

The aim of our study was to estimate the case fatality of a severe exacerbation from long-term survival data presented in the literature. A literature search identified studies reporting ≥1.5 yr survival after a severe chronic obstructive pulmonary disease (COPD) exacerbation resulting in hospitalisation. The survival curve of each study was divided into a critical and a stable period. Mortality during the stable period was then estimated by extrapolating the survival curve during the stable period back to the time of exacerbation onset. Case fatality was defined as the excess mortality that results from an exacerbation and was calculated as 1 minus the (backwardly) extrapolated survival during the stable period at the time of exacerbation onset. The 95% confidence intervals (CI) of the estimated case fatalities were obtained by bootstrapping. A random effect model was used to combine all estimates into a weighted average with 95% CI. The meta-analysis based on six studies that fulfilled the inclusion criteria resulted in a weighted average case-fatality rate of 15.6% (95% CI 10.9–20.3), ranging from 11.4% to 19.0% for the individual studies. A severe COPD exacerbation requiring hospitalisation not only results in higher mortality risks during hospitalisation, but also in the time-period after discharge and contributes substantially to total COPD mortality.
Interstitial lung disease guideline
Authors: A U Wells, N Hirani
Journal: Thorax (2008)

BAL, bronchoalveolar lavage; FEV 1 , forced expiratory volume in 1 s; FVC, forced vital capacity; HRCT, high resolution computed tomography; ILD, interstitial lung disease; P(A-a)O 2 , difference between alveolar and arterial pressure; PaO 2 , arterial oxygen tension; TLCO, carbon monoxide transfer factor; VC, vital capacity.*Modified from American Thoracic Society/European Respiratory Society recommendations. 2 {In the immunocompetent adult the presence of all of the major diagnostic criteria as well as at least three of the four minor criteria increases the likelihood of a correct clinical diagnosis of IPF.{The requirement for transbronchial lung biopsy/bronchoalveolar lavage within the diagnostic criteria for IPF is currently under review. Lung function testing in ILDc All patients with ILD should have resting spirometric and gas transfer measurement at presentation, which together provide a reasonable measure of disease severity.[C] c In idiopathic pulmonary fibrosis (IPF) and fibrotic nonspecific interstitial pneumonia (NSIP), carbon monoxide transfer factor (TLCO) levels at presentation are a more reliable guide to outcome than other resting lung function variables.A TLCO level of less than 40% is indicative of advanced disease in fibrotic idiopathic interstitial pneumonia (IIP).[B] c In IPF a fall from baseline of >10% in forced vital capacity (FVC) or >15% in TLCO in the first 6-12 months identifies patients with a much higher mortality.[B] c Desaturation during the 6 minute walk test at presentation is a stronger prognostic determinant in IPF than resting lung BTS guideline
Increasing oxidative stress and inflammation in patients with exacerbated chronic obstructive pulmonary disease (COPD) and their association with lung function
Authors: Velin Stratev, Jordan Petev, Sonya Galcheva, Marinka Peneva
Journal: European Respiratory Journal (2012)

Oxidative stress and chronic inflammation are the milestones in pathogenesis of COPD. It is assumed that their increase is associated with a worse lung function and frequent exacerbations.  Our aim was to assess changes in antioxidant enzymes superoxide-dismutase (SOD) and glutathione-peroxidase (GPx) activities and inflammatory markers in patients with exacerbated COPD, stable COPD and healthy controls and their association with airway obstruction.  We performed a cross-sectional study among 244 participants (mean age 60.5±9.5 years) divided into 3 groups: 76 were with exacerbated COPD (group 1), 65 were with stable COPD (group 2) and 103 were matched healthy subjects (group 3). We performed a questionnaire to define pack years, spirometry and biochemical tests. Oxidative stress was measured by erythrocyte activities of SOD and GPx.  Compared to the control group, patients from group 1 had significantly lower SOD and GPx activities (p  The present study suggests that there is an increased oxidative stress and inflammation in patients with COPD in exacerbation and there is a relationship with the severity of the disease.
The association between the<i>COL12A1</i>gene and anterior cruciate ligament ruptures
Authors: M. Posthumus, A. V. September, D. O'Cuinneagain, W. van der Merwe, M. P. Schwellnus, M. Collins
Journal: British Journal of Sports Medicine (2009)

Background Anterior cruciate ligament (ACL) ruptures are among the most severe musculoskeletal soft tissue injuries. However, the exact mechanisms which cause these acute injuries are unknown. Recently, sequence variants within two genes, namely COL1A1 and COL5A1 , which code for the α1 chains of types I and V collagen respectively, were shown to be associated with ACL ruptures. Type XII collagen, similarly to types I and V collagen, is a structural component of the ligament fibril and is encoded by a single gene, COL12A1 . Objective The aim of this study was to investigate whether sequence variants within COL12A1 are associated with ACL ruptures. Methods One hundred and twenty-nine (38 female) participants with clinically and surgically diagnosed ACL ruptures, as well as 216 (83 female) physically active controls participants (CON) without any history of ACL injury were included in this case-control genetic association study. All participants were genotyped for the Alu I and Bsr I restriction fragment length polymorphisms (RFLPs) within COL12A1 . Results The AA genotype of the COL12A1 Alu I RFLP was significantly over-represented in the female (OR=2.4, 95% CI 1.0 to 5.5, p=0.048), but not male (p=0.359) ACL participants. There were no genotype differences between the ACL and CON group for the Bsr I RFLP. Conclusion The COL12A1 Alu I RFLP is associated with ACL ruptures among female participants in this study. The results suggest that females with an AA genotype are at increased risk of ACL ruptures. These initial genetic association studies should be explored further and, if repeated, incorporated into multifactorial models developed to identify predisposed individuals.
Intravenous Sildenafil Is a Potent Pulmonary Vasodilator in Children With Congenital Heart Disease
Authors: Ingram Schulze-Neick, Paulina Hartenstein, Jia Li, Brigitte Stiller, Nicole Nagdyman, Michael Hübler, Ghazwan Butrous, Andy Petros, Peter Lange, Andrew N. Redington
Journal: Circulation (2003)

Increased pulmonary vascular resistance (PVR) because of congenital heart disease (CHD) may be caused by a dysfunction in endogenous pulmonary endothelial nitric oxide (NO) production. In other forms of pulmonary vascular disease with increased PVR, an elevated activity of a phosphodiesterase type 5 (PDE-5), responsible for the degradation of cyclic guanidine monophosphate (cGMP), the second messenger of endothelially produced NO, has been demonstrated. This study compares the effects of inhaled NO before and after the specific inhibition of the PDE-5 by intravenous sildenafil (Viagra) in pre- and postoperative children with increased PVR because of CHD.12 children with congenital heart disease (age 0.2 to 15.7 years, median 2.4 years) and increased mean pulmonary arterial pressure, and 12 postoperative children (age 0.11 to 0.65 years, median 0.32 years) with increased PVR (8.3+/-1.0 Wood Units*m2) were studied during cardiac catheterization ("cath laboratory"), or within 2 hours after return from cardiac surgery ("post op"), respectively. All were sedated, tracheally intubated and paralyzed. During alveolar hyperoxygenation (FiO2=0.65), the effects of inhaled NO (20 ppm) were compared before and after the stepwise infusion of sildenafil ("cath laboratory", 1 mg/kg; post op, 0.25 mg/kg). Intravenous sildenafil more effectively reduced PVR than NO (11.5% versus 4.3% in the "cath laboratory" patient group, P<0.05, and 25.8% versus 14.6% in the post op patient group, P=0.09. The increase in cGMP in response to NO was potentiated (2- to 2.4-fold) by PDE-5 inhibition. While the vasodilating effects of sildenafil showed pulmonary selectivity, its infusion was associated with increased intrapulmonary shunting in the postoperative patients (Qs/Qt=16.5+/-4.7% to 25.5+/-18.2% P=0.04).Intravenous sildenafil is as effective as inhaled NO as a pulmonary vasodilator in children with congenital heart disease. Although clinically insignificant in this study, increased intrapulmonary shunting with sildenafil may be disadvantageous in some patients after CHD surgery.
Relations in biomedical ontologies.
Authors: Barry Smith, Werner Ceusters, Bert Klagges, Jacob Köhler, Anand Kumar, Jane Lomax, Chris Mungall, Fabian Neuhaus, Alan L Rector, Cornelius Rosse
Journal: Genome biology (2005)

Abstract To enhance the treatment of relations in biomedical ontologies we advance a methodology for providing consistent and unambiguous formal definitions of the relational expressions used in such ontologies in a way designed to assist developers and users in avoiding errors in coding and annotation. The resulting Relation Ontology can promote interoperability of ontologies and support new types of automated reasoning about the spatial and temporal dimensions of biological and medical phenomena.
Xpert MTB/RIF versus sputum microscopy as the initial diagnostic test for tuberculosis: a cluster-randomised trial embedded in South African roll-out of Xpert MTB/RIF
Authors: Gavin J Churchyard, Wendy S Stevens, Lerole D Mametja, Kerrigan M McCarthy, Violet Chihota, Mark P Nicol, Linda K Erasmus, Norbert O Ndjeka, Lindiwe Mvusi, Anna Vassall, Edina Sinanovic, Helen S Cox, Christopher Dye, Alison D Grant, Katherine L Fielding
Journal: The Lancet Global Health (2015)

In South Africa, sputum smear microscopy has been replaced with Xpert MTB/RIF as the initial diagnostic test for tuberculosis. In a pragmatic parallel cluster-randomised trial, we evaluated the effect on patient and programme outcomes.We randomly allocated 20 laboratories (clusters) in medium-burden districts of South Africa to either an Xpert (immediate Xpert) or microscopy (Xpert deferred) group (1:1), stratified by province. At two primary care clinics per laboratory, a systematic sample of adults giving sputum for tuberculosis investigation was assessed for eligibility. The primary outcome was mortality at 6 months from enrolment. Masking of participants' group allocation was not possible because of the pragmatic trial design. The trial is registered with the ISRCTN registry (ISRCTN68905568) and the South African Clinical Trial Register (DOH-27-1011-3849).Between June and November, 2012, 4972 people were screened, and 4656 (93·6%) enrolled (median age 36 years; 2891 [62%] female; 2212 [62%] reported being HIV-positive). There was no difference between the Xpert and microscopy groups with respect to mortality at 6 months (91/2324 [3·9%] vs 116/2332 [5·0%], respectively; adjusted risk ratio [aRR] 1·10, 95% CI 0·75-1·62]).Xpert did not reduce mortality at 6 months compared with sputum microscopy. Improving outcomes in drug-sensitive tuberculosis programmes might require not only better diagnostic tests but also better linkage to care.Bill & Melinda Gates Foundation.
Coffee Consumption and Development of Type 2 Diabetes—Reply
Authors: Rob M. van Dam, Frank B. Hu
Journal: JAMA (2005)

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