tbuckley/cabot-search huggingface dataset:
Combination therapy for pulmonary arterial hypertension: still more questions than answers
Authors: M.M. Hoeper, A.T. Dinh-Xuan
Journal: European Respiratory Journal (2004)

As pulmonary arterial hypertension (PAH) is a disease with varying patho-aetiology 1, attempting to arrest its natural progression with a single type of pharmacological molecule might, sometimes, simply not be enough. As with systemic arterial hypertension, combination therapy has been proposed as an attractive, and logical, concept for the treatment of PAH in the future 2, and this concept is slowly creeping into today's clinical practice. The prospect of combination treatment is, theoretically, highly promising. However, the evidence supporting this concept remains weak.

In the past few years, three classes of substances have emerged as effective treatments for PAH: prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors 2. These substances act by different modes of action. Prostanoids replace endogenous prostacyclin, production of which is decreased or absent in the pulmonary vessels of PAH patients 3, 4, and exert vasodilatory and antiproliferative effects predominantly via the intracellular second messenger, cyclic adenosine 5′-monophosphate (cAMP). Endothelin-1 is overexpressed in PAH and causes deleterious effects such as pulmonary vasoconstriction and vascular smooth muscle cell proliferation 5; …
SOME BIOLOGICAL PROPERTIES OF PNEUMOCOCCUS TYPE 37 AND THE CHEMISTRY OF ITS CAPSULAR POLYSACCHARIDE
Authors: Judith C. Knecht, Gerald Schiffman, Robert Austrian
Journal: The Journal of Experimental Medicine (1970)

Pneumococcus Type 37, like pneumococcus Type 3, is characterized by the production of large mucoid colonies on the surface of solid media and by its very large capsule. It differs from the highly virulent pneumococcus Type 3 in that it is only slightly virulent for mice and rats and is isolated infrequently from man. A study of the behavior of pneumococcus Type 37 in systems comparable to those used in the study of pneumococcus Type 3 and an examination of the chemical structure of the capsule of pneumococcus Type 37 are described. The capsular polysaccharide of pneumococcus Type 37 is a viscous, optically inactive polymer composed of 95% hexose. Glucose is obtained in 88% yield upon acid hydrolysis. Periodate oxidation studies and the behavior of the polysaccharide on acid hydrolysis suggest that the molecule consists of a core of repeating units of 1,3 glucosyl-glucose to which short chains of glucose are attached at frequent intervals. Isolation of a disaccharide, the properties of which are identical with those of sophorose (beta1 --> 2 glucosyl-glucose), and of a trisaccharide are described. A tentative structure for the capsular polysaccharide of pneumococcus Type 37 is proposed.
In vivo leucocyte migration in Behçet's syndrome.
Authors: J Efthimiou, I.E Addison, B.V Johnson
Journal: Annals of the Rheumatic Diseases (1989)

Serial studies of leucocyte migration in vivo were carried out in 15 patients with Behçet9s syndrome using a skin window technique. Where possible, patients with and without active disease were studied during and in the absence of treatment. In patients with active disease neutrophil migration was frequently greater than normal, particularly with respect to numbers of cells migrating. There was also an increased frequency of emigrating neutrophils with less or more nuclear lobes than normal. In three patients in whom function of skin window neutrophils was studied nitroblue tetrazolium reduction and phagocytosis and killing of Candida guilliermondiae were normal. The monocyte component of the skin window was more often reduced in patients than in normal controls. Corticosteroid treatment did not exert a major effect on leucocyte migration, though the doses involved were relatively small. Neutrophil abnormalities were common in patients and particularly those with active disease. These results suggest that neutrophil hyperactivity may have an important role in the pathogenesis of Behçet9s syndrome.
Management of Fibromyalgia Syndrome
Authors: Don L. Goldenberg, Carol Burckhardt, Leslie Crofford
Journal: JAMA (2004)

The optimal management of fibromyalgia syndrome (FMS) is unclear and comprehensive evidence-based guidelines have not been reported.To provide up-to-date evidence-based guidelines for the optimal treatment of FMS. DATA SOURCES, SELECTION, AND EXTRACTION: A search of all human trials (randomized controlled trials and meta-analyses of randomized controlled trials) of FMS was made using Cochrane Collaboration Reviews (1993-2004), MEDLINE (1966-2004), CINAHL (1982-2004), EMBASE (1988-2004), PubMed (1966-2004), Healthstar (1975-2000), Current Contents (2000-2004), Web of Science (1980-2004), PsychInfo (1887-2004), and Science Citation Indexes (1996-2004). The literature review was performed by an interdisciplinary panel, composed of 13 experts in various pain management disciplines, selected by the American Pain Society (APS), and supplemented by selected literature reviews by APS staff members and the Utah Drug Information Service. A total of 505 articles were reviewed.There are major limitations to the FMS literature, with many treatment trials compromised by short duration and lack of masking. There are no medical therapies that have been specifically approved by the US Food and Drug Administration for management of FMS. Nonetheless, current evidence suggests efficacy of low-dose tricyclic antidepressants, cardiovascular exercise, cognitive behavioral therapy, and patient education. A number of other commonly used FMS therapies, such as trigger point injections, have not been adequately evaluated.Despite the chronicity and complexity of FMS, there are pharmacological and nonpharmacological interventions available that have clinical benefit. Based on current evidence, a stepwise program emphasizing education, certain medications, exercise, cognitive therapy, or all 4 should be recommended.
Endogenous and exogenous opiates modulate the development of parent–infant attachment
Authors: James Edward Swain, Linda C. Mayes, James F. Leckman
Journal: Behavioral and Brain Sciences (2005)

in addition to endogenously produced opiates, which are part of normal affiliative neurocircuitry and attachment formation, exogenous opiates – such as drugs of addiction and abuse – may affect affiliation. we consider possible modulatory effects of such exogenous opiates on the development of early parent–infant attachment from both parents' and infants' perspectives.
Eradicating H pylori
Authors: Brendan Delaney, Paul Moayyedi
Journal: BMJ (2004)

traditional approaches and positron emission tomography. 3 Non-oncological applicationsA worldwide fall in autopsies has prompted a search for a minimally invasive alternative.Attempting to provide an acceptable alternative, whole body MRI has been shown to be effective in the gross assessment of the corpse, helping to identify sites suitable for percutaneous biopsy, particularly in immunocompromised hosts. 9Whole body MRI has been similarly successful in whole body fat measurements and body composition research, and more recently as a primary diagnostic tool in patients with polymyositis. 10 11The advent of molecular imaging, fusing the specificity of molecular technology with the spatial resolution of imaging, is likely to herald many new scanning applications for whole body sequences. 12
The Management of Chronic Arthritis and other Rheumatic Diseases among Soldiers of the United States Army
Authors: P. S. Hench, E. W. Boland
Journal: Annals of the Rheumatic Diseases (1946)

1 Four common rheumatic diseases- rheumatoid arthritis, rheumatic fever, osteo-arthritis, and muscular rheumatism-accounted for about 80% of these cases (Table 1).The subsequent
HCV-associated cryoglobulinemic vasculitis: triple/dual antiviral treatment and/or rituximab? Reply to the comment by Ignatova<i>et al</i>
Authors: David Saadoun, Patrice Cacoub
Journal: Annals of the Rheumatic Diseases (2014)

The cerebral circulation of 25 normal term infants was investigated using continuous wave Doppler ultrasound. Serial blood flow velocity signals were obtained from the common carotid and anterior cerebral arteries during the first week of life. The records were processed using a frequency spectrum analyser to provide cerebral blood velocity waveforms. The pulsatility index (PI), A/B ratio, and rise and fall slope of the waveforms were calculated. The results indicated that cerebrovascular resistance was raised appreciably on day 1 of life compared with later in the first week. In 18 of 25 infants (72%) there was no continuous carotid blood flow in the first hours of life. We suggest that the human cerebral circulation adapts to the process of birth in a similar fashion to that of animal models.
Increased rectal cell proliferation following alcohol abuse
Authors: U A Simanowski
Journal: Gut (2001)

Epidemiological data indicate an increased risk for rectal cancer following chronic alcohol consumption. As chronic ethanol ingestion leads to rectal hyperregeneration in experimental animals, indicating a state of increased susceptibility to carcinogens, we studied cell proliferation in alcohol abusers.Rectal biopsies were taken from 44 heavy drinkers and 26 controls. Cell proliferation, including proliferative compartment size, was measured by immunohistological staining for proliferative cell nuclear antigen (PCNA) and Ki67, and by in situ hybridisation for histone H3. Quantification of cell proliferation using PCNA staining was evaluated in 27 alcohol abusers and 12 controls. In addition, immunohistology was performed for cytokeratins and gene products of Rb1, bcl-2, and p53.Heavy drinking resulted in increased cell proliferation of the rectal mucosa, as shown by increased detection of different proliferation markers. However, cell differentiation regarding cytokeratin expression patterns was unchanged as well as regulatory factors involved in carcinogenesis and/or apoptosis.Chronic alcohol abuse leads to rectal mucosal hyperproliferation in humans, a condition associated with an increased cancer risk.
Inhaled corticosteroids and the growth of lung function in children
Authors: M. Silverman
Journal: European Respiratory Journal (2004)

This month's edition of the European Respiratory Journal contains two papers that address the important topic of the effect of inhaled corticosteroids (ICS) on lung development in childhood 1, 2. The papers are important because: 1) they raise important methodological issues concerning the design of outcome studies in children; 2) they illustrate different approaches to the measurement of lung function in different age groups (preschool children and teenagers, respectively); 3) they raise questions about the relationship between the structure and function in the developing lung; and 4) they fuel the debate about the appropriate choice of outcomes in managing ICS therapy in children. These points, in turn, are considered below.

First, the design of the two studies is quite different. Devulapalli et al. 1 carried out a longitudinal observational study of a population sample in which young children who were prescribed ICS for “recurrent bronchial obstruction” (undefined) were compared with untreated symptomatic and symptom-free groups. Although the design is justified as being “based upon … real life”, it suffers from the shortfall that an independent effect of ICS on functional outcome cannot be deduced from the results presented. At best, it is possible to conclude that both treated and untreated young children with recurrent bronchial obstruction appear functionally to return towards normal by 2 yrs of age. Multivariate analysis might have added strength to the assumption that this process was indeed related in someway to ICS therapy, rather than being simply …
Interactions between Angiotensin II and NF-κB–Dependent Pathways in Modulating Macrophage Infiltration in Experimental Diabetic Nephropathy
Authors: Fiona T.H. Lee, Zemin Cao, David M. Long, Sianna Panagiotopoulos, George Jerums, Mark E. Cooper, Josephine M. Forbes
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. NF-κB-dependent pathways play an important role in macrophage infiltration and kidney injury. NF-κB is regulated by angiotensin II (AII). However, the role of this pathway in diabetic nephropathy has not been clearly delineated. First, the activation of NF-κB, monocyte chemoattractant protein-1 (MCP-1), and macrophage infiltration in the diabetic kidney were explored, in a temporal manner. The active subunit of NF-κB, p65, was elevated in the diabetic animals in association with increased MCP-1 gene expression and macrophage infiltration. Second, the effects of treatment for 4 wk with the AII type 1 receptor antagonist valsartan, the AII type 2 receptor antagonist PD123319, or pyrrolidine dithiocarbamate, an inhibitor of NF-κB and on these parameters were assessed. These treatments were associated with a reduction in p65 activation, MCP-1 gene expression, and macrophage infiltration. These findings demonstrate a role for activation of NF-κB, in particular the p65 subunit, in the pathogenesis of early renal macrophage infiltration in experimental diabetes. In the context of the known proinflammatory effects of AII, it is postulated that the renoprotection conferred by angiotensin II receptor antagonism is at least partly related to the inhibition of NF-κB–dependent pathways.
Increased oxygen pulse after lung volume reduction surgery is associated with reduced dynamic hyperinflation
Authors: Matthew R. Lammi, David Ciccolella, Nathaniel Marchetti, Malcolm Kohler, Gerard J. Criner
Journal: European Respiratory Journal (2012)

Stroke volume augmentation during exercise is limited in chronic obstructive pulmonary disease patients because of decreased preload from dynamic hyperinflation (DH). We hypothesised that oxygen pulse and pulse pressure (PP) improve following lung volume reduction surgery (LVRS), and the magnitude of improvement correlates with reduction in DH. We compared 16 emphysema patients undergoing LVRS with six emphysema patients not undergoing LVRS. Oxygen pulse and PP were calculated from maximal cardiopulmonary exercise tests at baseline and 6 months. End-expiratory lung volume (EELV)/total lung capacity (TLC) represented DH. Comparisons were made between baseline and 6 months at metabolic isotimes (per cent maximal carbon dioxide production ( V ′ CO 2 ,max )). At baseline, the LVRS group was older with higher forced expiratory volume in 1 s, but had similar hyperinflation to the non-LVRS group. At 6 months, oxygen pulse (50%, 75%, and 100% V ′ CO 2 ,max ) and PP (50% and 75% V ′ CO 2 ,max ) increased in the LVRS, but not in the non-LVRS group. Baseline functional residual capacity/TLC inversely correlated with resting oxygen pulse (r= -0.449, p=0.04). Decreased EELV/TLC correlated with increased oxygen pulse at 75% (r= -0.487, p=0.02) and 100% V ′ CO 2 ,max (r= -0.548, p=0.008). LVRS led to increased oxygen pulse and PP during exercise at metabolic isotimes 6 months following surgery. Reductions in DH correlated with increases in oxygen pulse during exercise. Reducing lung volume may improve stroke volume response to exercise by decreasing DH.
Tramadol and Flurbiprofen Depress the Cytotoxicity of Cisplatin via Their Effects on Gap Junctions
Authors: Bo He, Xuhui Tong, Lingzhi Wang, Qin Wang, Hua Ye, Bing Liu, Xiaoting Hong, Liang Tao, Andrew L. Harris
Journal: Clinical Cancer Research (2009)

Cancer patients are often concurrently treated with analgesics and antineoplastic drugs, yet the influence of analgesic agents on therapeutic activity of antineoplastic drugs is largely unexplored. This study investigates the effects of three commonly used analgesics, which produce analgesia by different mechanisms, on cytotoxicity induced by cisplatin, a widely used antitumor agent, and the relation between those effects and modulation of gap junction function by the analgesics.The role of gap junctions in the modulation of cisplatin toxicity is explored by manipulation of connexin expression, and gap junction presence and function, using clinically relevant concentrations of the analgesics and cisplatin.Short-term exposure of transformed cells to cisplatin reduced the clonogenic survival in low-density cultures (without gap junction formation) and in high density (with gap junction formation), but the toxic effect was greater at high density. In the absence of connexin expression or with block of connexin channels, cell density had no effect on cisplatin toxicity. Tramadol and flurbiprofen, but not morphine, significantly reduced cisplatin cytotoxicity, but this effect required functional gap junctions between the cells. Tramadol and flurbiprofen inhibited dye-coupling through gap junctions, but morphine did not.The results suggest that the density dependence of cisplatin toxicity is mediated by gap junctions. They further indicate that tramadol and flurbiprofen depress cisplatin cytotoxicity through inhibition of gap junction activity, and more generally, that agents that depress junctional communication can counteract the effects of antitumor agents.
Traffic related air pollution as a determinant of asthma among Taiwanese school children
Authors: B-F Hwang
Journal: Thorax (2005)

<b>Background:</b> There is evidence that long term exposure to ambient air pollution increases the risk of childhood asthma, but the role of different sources and components needs further elaboration. To assess the effect of air pollutants on the risk of asthma among school children, a nationwide cross sectional study of 32 672 Taiwanese school children was conducted in 2001. <b>Methods:</b> Routine air pollution monitoring data for sulphur dioxide (SO<sub>2</sub>), nitrogen oxides (NOx), ozone (O<sub>3</sub>), carbon monoxide (CO), and particles with an aerodynamic diameter of 10 μm or less (PM<sub>10</sub>) were used. Information on individual characteristics and indoor environments was from a parent administered questionnaire (response rate 93%). The exposure parameters were calculated using the mean of the 2000 monthly averages. The effect estimates were presented as odds ratios (ORs) per 10 ppb changes for SO<sub>2</sub>, NOx, and O<sub>3</sub>, 100 ppb changes for CO, and 10 μg/m<sup>3</sup> changes for PM<sub>10</sub>. <b>Results:</b> In a two stage hierarchical model adjusting for confounding, the risk of childhood asthma was positively associated with O<sub>3</sub> (adjusted OR 1.138, 95% confidence interval (CI) 1.001 to 1.293), CO (adjusted OR 1.045, 95% CI 1.017 to 1.074), and NOx (adjusted OR 1.005, 95% CI 0.954 to 1.117). Against our prior hypothesis, the risk of childhood asthma was weakly or not related to SO<sub>2</sub> (adjusted OR 0.874, 95% CI 0.729 to 1.054) and PM<sub>10</sub> (adjusted OR 0.934, 95% CI 0.909 to 0.960). <b>Conclusions:</b> The results are consistent with the hypothesis that long term exposure to traffic related outdoor air pollutants such as NOx, CO, and O<sub>3</sub> increases the risk of asthma in children.
The Behavioral Determinants of Exercise: Implications for Physical Activity Interventions
Authors: Nancy E. Sherwood, Robert W. Jeffery
Journal: Annual Review of Nutrition (2000)

In light of the well-documented health benefits of physical activity and the fact that the majority of adult men and women are inactive, promoting regular physical activity is a public health priority. This chapter reviews current research findings regarding the determinants of exercise behavior. It also discusses the implications of this knowledge for individual and public health recommendations and intervention strategies for promoting physical activity. The discussion is predicated on the belief that physical activity is a complex, dynamic process. During their lives, individuals typically move through various phases of exercise participation that are determined by diverse factors. This chapter discusses physical activity determinants in two broad categories: individual characteristics, including motivations, self-efficacy, exercise history, skills, and other health behaviors; and environmental characteristics such as access, cost, and time barriers and social and cultural supports.
Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for Patients With Node-Positive, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Edward H. Romond, Jong-Hyeon Jeong, Priya Rastogi, Sandra M. Swain, Charles E. Geyer, Michael S. Ewer, Vikas Rathi, Louis Fehrenbacher, Adam Brufsky, Catherine A. Azar, Patrick J. Flynn, John L. Zapas, Jonathan Polikoff, Howard M. Gross, David D. Biggs, James N. Atkins, Elizabeth Tan-Chiu, Ping Zheng, Greg Yothers, Eleftherios P. Mamounas, Norman Wolmark
Journal: Journal of Clinical Oncology (2012)

Purpose Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2–positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. Patients and Methods In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified. Results At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. Conclusion The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.
Pandemic Influenza Vaccine Policy — Considering the Early Evidence
Authors: Kathleen M. Neuzil
Journal: New England Journal of Medicine (2009)

Policy decisions regarding influenza rest on judgments about the behavior of the virus, the impact of the disease and our ability to interdict its course.But the virus is capricious, the disease elusive, and our remedies imperfect," said a report on the 1976 swine-flu epidemic at Fort Dix. 1Two peer-reviewed articles now publicly available at NEJM.org, by Greenberg et al. (ClinicalTrials.gov number, NCT00938639) 2 and Clark et al. (NCT00943358), 3 describe preliminary data on the immunogenicity of the influenza A (H1N1) 2009 monovalent vaccine.These data have been eagerly anticipated, as governments, public health officials, and other stakeholders respond to the first influenza pandemic in over 40 years.The authors and their collaborators are to be commended for their prompt execution of the trials and rapid sharing of the results.