tbuckley/cabot-search huggingface dataset:
Collateral ventilation by diffusion across the alveolar walls and the exchange of inert gases in the lung
Authors: SC Luijendijk, WR de Vries, A Zwart
Journal: European Respiratory Journal (1991)

The underlying hypothesis of this study is that collateral ventilation by diffusion of occluded air spaces in the lungs of patients with chronic obstructive pulmonary disease (COPD) may play a substantial role in the pulmonary gas exchange of these patients. Using a related lung model we have simulated: a) the multiple-breath washout of helium (He) and sulphur hexafluoride (SF6) from the alveolar space, and b) the washout of inert tracer gases with different blood-gas partition coefficients, range 0.01-330, from mixed venous blood. These computations were carried out for different values of the collateral diffusion capacity (CDC). Next, the results obtained at each individual value of CDC were used to compute the breath number (NCR) at the crossing-over of the He-SF6 washout curves and the inert gas shunt fraction QS/QC. NCR and QS/QC range up to about 100 and 0.04, respectively, when CDCSF6 ranges down to about 0.1 ml.min-1.mmHg-1. These ranges for NCR and QS/QC, and the typical finding of relatively large values for NCR in combination with small values for QS/QC, are also reported in the literature for patients with COPD. These agreements thus support our hypothesis. In line with the small values for QS/QC, our results further indicate that even large, well-perfused, occluded air spaces in the lung will hardly affect the recovered ventilation/perfusion distribution obtained from inert gas data when CDCSF6 exceeds 0.1 ml.min-1.mmHg-1.
The modified BODE index: validation with mortality in COPD
Authors: C. G. Cote, V. M. Pinto-Plata, J. M. Marin, H. Nekach, L. J. Dordelly, B. R. Celli
Journal: European Respiratory Journal (2008)

Peak oxygen uptake (V'(O(2))) remains the gold standard measurement of exercise capacity and has been associated with survival. A modified BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index replacing the 6-min walk distance (6MWD) with V'(O(2)) as % predicted (mBODE%) has been developed and found to have excellent correlation with the conventional BODE index. The objectives of the present study were to compare the ability of the conventional BODE and the mBODE% to predict mortality in 444 patients with chronic obstructive pulmonary disease (COPD) followed for a mean+/-SD period of 71+/-34 months. Anthropometrics, spirometry, lung volumes, comorbidity, cardiopulmonary cyclo-ergometry test and 6MWD were determined at entry. The mean BODE indices for the cohort were: BODE 4.1+/-2 and mBODE% 5.5+/-2. Both indices were significantly correlated with mortality. Logistic regression analysis with COPD survival as the dependent variable identified the BODE index, Charlson's and exercise capacity (in W) as variables associated with this outcome. In conclusion, the conventional BODE index, which uses the 6-min walk distance, predicts mortality in chronic obstructive pulmonary disease as well as the modified index using peak oxygen uptake. The results support the use of the simpler index, which includes the 6-min walk distance in the comprehensive evaluation of patients with chronic obstructive pulmonary disease.
Hematopoietic Cell Transplantation–Specific Comorbidity Index Predicts Inpatient Mortality and Survival in Patients Who Received Allogeneic Transplantation Admitted to the Intensive Care Unit
Authors: Ulas D. Bayraktar, Elizabeth J. Shpall, Ping Liu, Stefan O. Ciurea, Gabriela Rondon, Marcos de Lima, Marylou Cardenas-Turanzas, Kristen J. Price, Richard E. Champlin, Joseph L. Nates
Journal: Journal of Clinical Oncology (2013)

To investigate the prognostic value of the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) in patients who received transplantation admitted to the intensive care unit (ICU).We investigated the association of HCT-CI with inpatient mortality and overall survival (OS) among 377 patients who were admitted to the ICU within 100 days of allogeneic stem-cell transplantation (ASCT) at our institution. HCT-CI scores were collapsed into four groups and were evaluated in univariate and multivariate analyses using logistic regression and Cox proportional hazards models.The most common pretransplantation comorbidities were pulmonary and cardiac diseases, and respiratory failure was the primary reason for ICU admission. We observed a strong trend for higher inpatient mortality and shorter OS among patients with HCT-CI values ≥ 2 compared with patients with values of 0 to 1 in all patient subsets studied. Multivariate analysis showed that patients with HCT-CI values ≥ 2 had significantly higher inpatient mortality than patients with values of 0 to 1 and that HCT-CI values ≥ 4 were significantly associated with shorter OS compared with values of 0 to 1 (hazard ratio, 1.74; 95% CI, 1.23 to 2.47). The factors associated with lower inpatient mortality were ICU admission during the ASCT conditioning phase or the use of reduced-intensity conditioning regimens. The overall inpatient mortality rate was 64%, and the 1-year OS rate was 15%. Among patients with HCT-CI scores of 0 to 1, 2, 3, and ≥ 4, the 1-year OS rates were 22%, 17%, 18%, and 9%, respectively.HCT-CI is a valuable predictor of mortality and survival in critically ill patients after ASCT.
Incidence of Non–AIDS-Defining Cancers Before and During the Highly Active Antiretroviral Therapy Era in a Cohort of Human Immunodeficiency Virus–Infected Patients
Authors: Magid Herida, Murielle Mary-Krause, Régis Kaphan, Jacques Cadranel, Isabelle Poizot-Martin, Christian Rabaud, Nathalie Plaisance, Hervé Tissot-Dupont, François Boue, Jean-Marie Lang, Dominique Costagliola
Journal: Journal of Clinical Oncology (2003)

To determine incidence of non-AIDS-defining cancers (NADC) in HIV-infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex.Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study.NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkin's disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2.Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.
Accuracy of Borg's ratings of perceived exertion in the prediction of heart rates during pregnancy.
Authors: M E O'Neill, K A Cooper, C M Mills, E S Boyce, S N Hunyor
Journal: British Journal of Sports Medicine (1992)

When using Borg's 6-20 scale during pregnancy, ratings of perceived exertion (RPE) did not significantly correlate with exercise heart rates (HR) (P greater than 0.05). The HR predicted from RPE significantly (P less than 0.05) underestimated the exercise HR in the second trimester during walking (Group 1: mean difference 16 beats min-1, n = 11), aerobics classes (Group 4: mean 15 beats min-1, n = 48) and circuit training (Group 3: mean 18 beats min-1, n = 24); and in the third trimester during cycling (Group 2: mean 16 beats min-1, n = 12) and aerobics classes (Group 5: mean 11 beats min-1, n = 29). Maximal individual HR under-estimations were large for each physical activity during pregnancy, with values up to 54 beats min-1. Consequently, exercise intensity should not be monitored solely with RPE during pregnancy.
Hepatic intestinal uptake and release of catecholamines in alcoholic cirrhosis. Evidence of enhanced hepatic intestinal sympathetic nervous activity.
Authors: J H Henriksen, H Ring-Larsen, N J Christensen
Journal: Gut (1987)

Hepatic intestinal and whole body plasma clearance and appearance of noradrenaline (NA) was quantified in patients with alcoholic cirrhosis (n = 12) and in controls (n = 6). As NA may be released as well as removed in the same vascular bed, infusion of tritium labelled NA (3H-NA) was carried out during hepatic vein catheterisation in order to determine both flux rates. In alcoholic cirrhosis plasma concentrations of endogenous NA and adrenaline (A) were significantly above control values (NA: median 2.4 v 1.7 nmol/l, p less than 0.02; A: 0.38 v 0.19 nmol/l, p less than 0.01). Whole body clearance of 3H-NA equal in the two groups (1.6 v 1.7 l/min, ns), while as the overall appearance rate of NA was significantly higher in alcoholic cirrhosis (4.2 v 2.6 nmol/min, p less than 0.02) indicating an enhanced sympathoadrenal activity in this group. The hepatic intestinal clearances of A, NA, and 3H-NA were not significantly different in patients and controls, but the estimated hepatic intestinal spillover rate of NA was 0.24 nmol/min in patients as compared with 0.0 nmol/min in controls (p less than 0.02). As a result of portosystemic shunting in cirrhosis the present estimation of NA spillover represents a minimum value. Our results indicate that the augmented circulating catecholamines in cirrhosis do not result from diminished removal but are contributed to from increased sympathetic nervous activity in the hepatic intestinal area (enhanced mesenteric sympathetic nervous activity).
Consistency of Phase III Clinical Trial Abstracts Presented at an Annual Meeting of the American Society of Clinical Oncology Compared With Their Subsequent Full-Text Publications
Authors: Vincent C. Tam, Sebastien J. Hotte
Journal: Journal of Clinical Oncology (2008)

Purpose This study aimed to determine the consistency of phase III clinical trial abstracts presented at American Society of Clinical Oncology (ASCO) Annual Meetings compared with their subsequent full-text publications. Methods We identified abstracts describing phase III clinical trials of chemotherapy, chemoradiotherapy, immunotherapy, and hormone therapy presented at the 36th ASCO Annual Meeting in May 2000. We searched MEDLINE and PubMed for all corresponding publications. Data were extracted from the abstracts and publications that met our inclusion criteria. Results A total of 192 abstracts were identified. Seventy-four abstracts met our inclusion criteria. Six years after the 2000 ASCO Meeting, 74% of abstracts had corresponding publications. The primary end point was stated in 34% of abstracts and 100% of published papers. The primary end point result differed by more than 5% between the abstract and publication in 42% of comparisons. The statistical significance of the primary end point and study conclusions were consistent between abstracts and subsequent publications in 89% and 91% of the comparisons, respectively. Abstracts selected as plenary or oral presentations were significantly more likely to be published. No factors predicted consistency for primary end point significance and overall conclusion between ASCO abstracts and their journal publications. Conclusion When carefully selected, ASCO Annual Meeting abstracts of phase III trials consistently reflect final published results, but some differences were observed that warrant caution in using abstract results to shape treatment decisions before full publication.
Regulation of myocardial and vascular alpha-adrenergic receptor affinity. Effects of guanine nucleotides, cations, estrogen, and catecholamine depletion.
Authors: W S Colucci, M A Gimbrone, R W Alexander
Journal: Circulation Research (1984)

The threshold sensitivity of cardiovascular tissues to alpha-adrenergic stimulation is determined largely by the affinity of alpha-adrenergic receptors for agonists. To determine whether changes in alpha-adrenergic receptor affinity could contribute to the regulation of cardiac and vascular responsiveness, we used the alpha-adrenergic-selective radioligands, [3H]prazosin, [3H]-WB-4101, and [3H]rauwalscine, to study and contrast the determinants of alpha-adrenergic receptor affinity in myocardium and vascular smooth muscle from the rat. In both tissues, l-epinephrine binding to the alpha 1-adrenergic receptor describes a shallow curve suggesting more than one affinity state. Computer analysis of binding to myocardial alpha 1-receptors indicates that 15% are of high affinity (Kd = 11 nM) and 85% are of low affinity (Kd = 400 nM). Expression of high affinity sites is magnesium dependent (maximum effect, 5-10 mM), and suppressed by the guanosine 5'-triphosphate analogue Gpp(NH)p (maximum effect, 1 mM) and sodium (maximum effect, 100-200 mM). In vascular smooth muscle, agonist-binding curves are also shallow and exhibit a similar response to that of Gpp(NH)p. Basal receptor affinity in myocardium is significantly higher (5.4-fold) than in vascular smooth muscle. Unlike vascular smooth muscle, in which alpha 1-adrenergic receptor affinity is increased by estrogen or reserpine treatment of the animal, the receptor in myocardium is unaffected by these treatments. In vascular smooth muscle, following reserpine-induced increase in alpha-adrenergic receptor affinity, the Gpp(NH)p effect is still present. Thus, alpha 1-adrenergic receptors in both myocardium and vascular smooth muscle exist in two affinity states and are subject to regulation by several factors, including guanine nucleotides, mono- and divalent cations, tissue of origin, sex hormones, and the level of sympathetic stimulation. Potentially, alterations in alpha 1-adrenergic receptor affinity, independent of a change in receptor number, may play an important role in the regulation of cardiovascular tissue responsiveness to catecholamines.
Influence of ribose, adenosine, and "AICAR" on the rate of myocardial adenosine triphosphate synthesis during reperfusion after coronary artery occlusion in the dog.
Authors: M Mauser, H M Hoffmeister, C Nienaber, W Schaper
Journal: Circulation Research (1985)

Recovery of adenosine triphosphate after myocardial ischemia is limited by the slow adenine nucleotide de novo synthesis and the availability of precursors of the nucleotide salvage pathways. We determined the adenine nucleotide de novo synthesis in the dog by infusion of [14C]glycine and the acceleration of adenine nucleotide built up by intracoronary infusion of ribose together with [14C]glycine or radiolabeled 5-amino-4-imidazolcarboxamide riboside or adenosine in the same animal model and with the same dosage of substrates (9 mmol) in postischemic and nonischemic myocardial tissue. After 45 minutes of occlusion of a side branch of the left coronary artery, the ischemic area was reperfused for 3 hours, and needle biopsies were taken for biochemical analysis. Adenine nucleotide de novo synthesis was found to be very slow (1.5 nmol/g wet weight per hour). The rate was doubled after ischemia. Adenine nucleotide synthesis was accelerated 5-fold by ribose, the basic substrate of the adenine nucleotide de novo synthesis, 9-fold by 5-amino-4-imidazolcarboxamide riboside, an intermediate of the adenine nucleotide de novo synthesis and 90-fold by adenosine, a substrate of the nucleotide salvage pathway. Therefore, only adenosine infusion resulted in a measurable increase of adenosine triphosphate levels after 3 hours of reperfusion, but over a longer time period, ribose or 5-amino-4-imidazol-carboxamide riboside also can be expected to replenish reduced myocardial adenosine triphosphate faster than adenine nucleotide de novo synthesis. Studies with radiolabeled 5-amino-4-imidazol-carboxamide riboside showed significant incorporation of radioactivity into 5-amino-4-imidazol-carboxamide ribose triphosphate which had also risen measurably during 5-amino-4-imidazol-carboxamide ribose infusion, and which is not normally found in heart muscle.
Osteoarthritis linkage scan: more loci for the geneticists to investigate
Authors: J Loughlin
Journal: Annals of the Rheumatic Diseases (2006)

Chromosomal loci potentially harbour osteoarthritis susceptibility genes, as shown by a genomewide linkage scan

Those investigating the molecular genetic basis of osteoarthritis must believe that all the hard work is beginning to reap rewards, as yet another linkage scan shows several interesting chromosomal loci potentially harbouring osteoarthritis susceptibility. In the September issue of the Annals of Rheumatic Diseases , Greig et al 1 reported the results of a comprehensive genomewide linkage scan performed on 202 families that contain individuals with nodal osteoarthritis, recruited from Nottinghamshire, UK.1 By using both a qualitative analysis (presence or absence of nodal osteoarthritis) and a quantitative analysis (severity of the disease), major hits were reported for chromosomes 3, 4, 8, 11 and 16. Intriguingly, the chromosome 3 and 16 hits overlap with osteoarthritis loci reported by other groups, implying that at least these two linkages are likely to be genuine.

So how does this latest linkage data fit in with what we currently know about the molecular genetic basis of osteoarthritis susceptibility? The Greig et al report1 is the fifth genomewide osteoarthritis linkage scan so far published, the others being conducted on affected-relative pairs collected in the UK,2, …
The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta.
Authors: A A Colletta, L M Wakefield, F V Howell, D Danielpour, M Baum, M B Sporn
Journal: Journal of Clinical Investigation (1991)

Recent experimental work has identified a novel intracellular binding site for the synthetic progestin, Gestodene, that appears to be uniquely expressed in human breast cancer cells. Gestodene is shown here to inhibit the growth of human breast cancer cells in a dose-dependent fashion, but has no effect on endocrine-responsive human endometrial cancer cells. Gestodene induced a 90-fold increase in the secretion of transforming growth factor-beta (TGF-beta) by T47D human breast cancer cells. Other synthetic progestins had no effect, indicating that this induction is mediated by the novel Gestodene binding site and not by the conventional progesterone receptor. Furthermore, in four breast cancer cell lines, the extent of induction of TGF-beta correlated with intracellular levels of Gestodene binding site. No induction of TGF-beta was observed with the endometrial cancer line, HECl-B, which lacks the Gestodene binding site, but which expresses high levels of progesterone receptor. The inhibition of growth of T47D cells by Gestodene is partly reversible by a polyclonal antiserum to TGF-beta. These data indicate that the growth-inhibitory action of Gestodene may be mediated in part by an autocrine induction of TGF-beta.
Letter: Diethylstillbestrol adenosis and dysfunctional uterine bleeding
Authors: H. O. Williamson
Journal: JAMA (1976)

<h3>To the Editor.—</h3> While evaluating the conditions of patients seen in consultation because of menstrual irregularities, we detected previously unsuspected vaginal adenosis in several. This prompted a review of the charts of patients with biopsy-proved vaginal adenosis; 15 of these had a documented history of diethylstilbestrol exposure. Seven patients had significant menstrual abnormalities, with five having been referred for this problem. A diagnosis of vaginal adenosis was made only after physical examination and iodine-staining raised the index of suspicion. One of the seven patients had conceived, and none was at risk for pregnancy. No pattern of menstrual irregularity emerged. Two had hemorrhaged and had been treated by dilation and curettage. Two others had androgenic disorders, including hirsutism and infrequent menses; one of these had been treated elsewhere by ovarian wedge resection. One with prolonged secondary amenorrhea was classed as having a hypothalamic disorder. Another, with infrequent menses, was treated with
Effect of Antioxidant Supplementation on Ozone-Induced Lung Injury in Human Subjects
Authors: JAMES M. SAMET, GARY E. HATCH, DONALD HORSTMAN, SUSAN STECK-SCOTT, LENORE ARAB, PHILIP A. BROMBERG, MARK LEVINE, WILLIAM F. MCDONNELL, ROBERT B. DEVLIN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

To determine whether antioxidants can influence human susceptibility to ozone (O(3))-induced changes in lung function and airway inflammation, we placed 31 healthy nonsmoking adults (18 to 35 yr old) on a diet low in ascorbate for 3 wk. At 1 wk, subjects were exposed to filtered air for 2 h while exercising (20 L/min/m(2)), and then underwent bronchoalveolar lavage (BAL) and were randomly assigned to receive either a placebo or 250 mg of vitamin C, 50 IU of alpha-tocopherol, and 12 oz of vegetable cocktail daily for 2 wk. Subjects were then exposed to 0.4 ppm O(3) for 2 h and underwent a second BAL. On the day of the O(3) exposure, supplemented subjects were found to have significantly increased levels of plasma ascorbate, tocopherols, and carotenoids as compared with those of the placebo group. Pulmonary function testing showed that O(3)-induced reductions in FEV(1) and FVC were 30% and 24% smaller, respectively, in the supplemented cohort. In contrast, the inflammatory response to O(3) inhalation, as represented by the percent neutrophils and the concentration of interleukin-6 recovered in the BAL fluid at 1 h after O(3) exposure was not different for the two groups. These data suggest that dietary antioxidants protect against O(3)-induced pulmonary function decrements in humans.
Response to ‘Assessment of vitiligo severity: patient-reported estimates are not accurate’
Authors: N.B. Silverberg, J.I. Silverberg
Journal: British Journal of Dermatology (2015)

Journal Article Response to ‘Assessment of vitiligo severity: patient‐reported estimates are not accurate’ Get access N.B. Silverberg, N.B. Silverberg Department of Dermatology and Pediatrics Mount Sinai St. Luke's‐Roosevelt and Beth Israel Medical Centers New York NY U.S.A Search for other works by this author on: Oxford Academic Google Scholar J.I. Silverberg J.I. Silverberg Departments of Dermatology, Preventive Medicine and Medical Social Sciences Northwestern University Feinberg School of Medicine Chicago IL 60611 U.S.ANorthwestern Medicine Multidisciplinary Eczema Center Chicago IL 60611 U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 5, 1 November 2015, Page 1340, https://doi.org/10.1111/bjd.14007 Published: 01 November 2015
Fist/Hipk3
Authors: Véronique Rochat-Steiner, Karin Becker, Olivier Micheau, Pascal Schneider, Kim Burns, Jürg Tschopp
Journal: The Journal of Experimental Medicine (2000)

Fas is a cell surface death receptor that signals apoptosis. Several proteins have been identified that bind to the cytoplasmic death domain of Fas. Fas-associated death domain (FADD), which couples Fas to procaspase-8, and Daxx, which couples Fas to the Jun NH2-terminal kinase pathway, bind independently to the Fas death domain. We have identified a 130-kD kinase designated Fas-interacting serine/threonine kinase/homeodomain-interacting protein kinase (FIST/HIPK3) as a novel Fas-interacting protein. Binding to Fas is mediated by a conserved sequence in the COOH terminus of the protein. FIST/HIPK3 is widely expressed in mammalian tissues and is localized both in the nucleus and in the cytoplasm. In transfected cell lines, FIST/HIPK3 causes FADD phosphorylation, thereby promoting FIST/HIPK3–FADD–Fas interaction. Although Fas ligand–induced activation of Jun NH2-terminal kinase is impaired by overexpressed active FIST/HIPK3, cell death is not affected. These results suggest that Fas-associated FIST/HIPK3 modulates one of the two major signaling pathways of Fas.