tbuckley/cabot-search huggingface dataset:
Pulmonary haemodynamics in obstructive sleep apnoea: time course and associated factors
Authors: H Schafer, E Hasper, S Ewig, U Koehler, J Latzelsberger, S Tasci, B Luderitz
Journal: European Respiratory Journal (1998)

Changes in pulmonary artery pressure within an obstructive apnoea and elevations of transmural pulmonary artery pressure (Ppa,tm) towards the end of apnoea are well known. The purpose of our study was to examine which factors contribute to the increase of Ppa,tm in an apnoea. In addition, the time course of Ppa,tm and associated factors during a sleep study was investigated. We analysed the association of changes in arterial oxygen saturation (Sa,O2), oesophageal pressure (Poes) to estimate intrathoracic pressure, systolic blood pressure (BPsys) to estimate left ventricular afterload, apnoea duration and the change in Ppa,tm (deltaPpa,tm) during the course of obstructive apnoeas. Consecutive apnoeas in nonrapid eye movement (NREM)-sleep at the beginning, the middle and the end of the sleep study were analysed in six patients with obstructive sleep apnoea. The mean systolic Ppa,tm was 28.0+/-12.1 mmHg at the beginning of apnoea and 38.6+/-15.5 mmHg at the end (deltaPpa,tm 10.5+/-7.4 mmHg; p&lt;0.0001). DeltaSa,O2 (p&lt;0.0001; odds ratio (OR) 1.45; confidence interval (CI) 1.20-1.76) and deltaPoes (p&lt;0.0001; OR 1.22; CI 1.11-1.34) were independently associated with deltaPpa,tm in a multiple regression analysis. Apnoea duration as well as deltaPoes, deltaPpa,tm and deltaSa,O2 were all significantly higher (p&lt;0.05) in apnoeas at the middle of the sleep study than at the beginning or the end. In conclusion, hypoxaemia and mechanical factors as an increase in negative thoracic pressure contribute to elevations of the transmural pulmonary artery pressure during an obstructive apnoea. The time course of pulmonary haemodynamics within a steep study reveals that the highest transmural pulmonary artery pressure occurs in the middle of the night with no progressive increase towards the end of the sleep study.
Paternity and Testicular Function Among Testicular Cancer Survivors Treated With Two to Four Cycles of Cisplatin-Based Chemotherapy
Authors: Marianne Brydøy, Sophie D. Fosså, Olbjørn Klepp, Roy M. Bremnes, Erik A. Wist, Tore Wentzel-Larsen, Olav Dahl
Journal: European Urology (2010)
Phase II Trial of Cisplatin, Gemcitabine, and Bevacizumab As First-Line Therapy for Metastatic Urothelial Carcinoma: Hoosier Oncology Group GU 04-75
Authors: Noah M. Hahn, Walter M. Stadler, Robin T. Zon, David Waterhouse, Joel Picus, Sreenivasa Nattam, Cynthia S. Johnson, Susan M. Perkins, Mary Jane Waddell, Christopher J. Sweeney
Journal: Journal of Clinical Oncology (2011)

Novel approaches are needed for patients with metastatic urothelial cancer (UC). This trial assessed the efficacy and toxicity of bevacizumab in combination with cisplatin and gemcitabine (CGB) as first-line treatment for patients with metastatic UC.Chemotherapy-naive patients with metastatic or unresectable UC received cisplatin 70 mg/m(2) on day 1, gemcitabine 1,000 to 1,250 mg/m(2) on days 1 and 8, and bevacizumab 15 mg/kg on day 1, every 21 days.Forty-three patients with performance status of 0 (n = 26) or 1 (n = 17) and median age of 66 years were evaluable for toxicity and response. Grade 3 to 4 hematologic toxicity included neutropenia (35%), thrombocytopenia (12%), anemia (12%), and neutropenic fever (2%). Grade 3 to 5 nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21%), hemorrhage (7%), cardiac (7%), hypertension (5%), and proteinuria (2%). Three treatment-related deaths (CNS hemorrhage, sudden cardiac death, and aortic dissection) were observed. Best response by Response Evaluation Criteria in Solid Tumors was complete response in eight patients (19%) and partial response in 23 patients (53%), for an overall response rate of 72%. Stable disease lasting ≥ 12 weeks occurred in four patients (9%), and progressive disease occurred in six patients (14%). With a median follow-up of 27.2 months (range, 3.5 to 40.9 months), median progression-free survival (PFS) was 8.2 months (95% CI, 6.8 to 10.3 months) with a median overall survival (OS) time of 19.1 months (95% CI, 12.4 to 22.7 months). The study-defined goal of 50% improvement in PFS was not met.CGB demonstrates promising OS and antiangiogenic treatment-related toxicities in the phase II setting of metastatic UC. The full risk/benefit profile of CGB in patients with metastatic UC will be determined by an ongoing phase III intergroup trial.
Stratified Care vs Step Care Strategies for Migraine
Authors: Richard B. Lipton, Walter F. Stewart, Andrew M. Stone, Miguel J. A. Láinez, James P. C. Sawyer
Journal: JAMA (2000)

3][4] Ultimately, the goal of optimal migraine care is to initiate effective treatment strategies as early as possible, thereby minimizing pain and disability. 43][4][5][6] In step care across attacks, patients begin with a nonspecific therapy (ie, a simple or combination analgesic).After treating several attacks, if the treatment result is unsatisfactory, patients recontact their clinician for treatment escalation.The process is repeated until a satisfactory treatment result is achieved.This approach, often advocated in managed care treatment guidelines, has a number of advantages and disadvantages. 5,6n step care within attacks, patients initially treat an attack with a nonspecific therapy.At a specific time
The incidence of hydroxyethyl starch-associated pruritus
Authors: M. Murphy, A.J. Carmichael, P.G. Lawler, M. White, N.H. Cox
Journal: British Journal of Dermatology (2001)

Journal Article The incidence of hydroxyethyl starch‐associated pruritus Get access M. Murphy, M. Murphy Departments of Dermatology and Intensive Care, South Cleveland Hospital, Middlesbrough, U.K. Departments of Dr Michelle Murphy, Department of Dermatology, Medical School, Framlington Place, University of Newcastle, Newcastle upon Tyne NE2 4HH, U.K. E‐mail: michmurphy@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar A.J. Carmichael, A.J. Carmichael Departments of Dermatology and Intensive Care, South Cleveland Hospital, Middlesbrough, U.K. Departments of Search for other works by this author on: Oxford Academic Google Scholar P.G. Lawler, P.G. Lawler Departments of Dermatology and Intensive Care, South Cleveland Hospital, Middlesbrough, U.K. Departments of Search for other works by this author on: Oxford Academic Google Scholar M. White, M. White Intensive Care and Search for other works by this author on: Oxford Academic Google Scholar N.H. Cox N.H. Cox Dermatology, Cumberland Infirmary, Carlisle, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 5, 1 May 2001, Pages 973–976, https://doi.org/10.1046/j.1365-2133.2001.04184.x Published: 01 May 2001
Long-range transport modeling of air pollution episodes.
Authors: F A de Leeuw, H J Leyssius
Journal: Environmental Health Perspectives (1989)

The air quality network in the Netherlands is based on a regular grid with an interstation distance of 30 to 40 km. In or close to source areas, a higher station density is realized. Atmospheric transport models form an intrinsic part of the air quality monitoring system. The models are constructed in such a way that only routinely available meteorological input data are needed. The models are applied for interpretation and generalization of the measurements in terms of contributions of source categories. In scenario studies, the potential effect of abatement strategies is explored. The output of the models consists of concentration and deposition fields of NOx, NO2, SO2, sulfate, and nitrate on the scale of the Netherlands or on the scale of northwestern Europe. In the present version the models are not directly suitable to estimate exposures to acidic aerosols; however, in combination with limited aerosol measurements, the model predictions can be used to provide information on the spatial and temporal distribution of acidic aerosols as needed for exposure assessment.
A role for sodium/calcium exchange in the action potential shortening caused by strophanthidin in guinea pig ventricular myocytes
Authors: A. J Levi
Journal: Cardiovascular Research (1993)

Objective: The aim was to investigate the nature of the membrane currents which underlie the shortening of the action potential in guinea pig cardiac myocytes upon exposure to the digitalis analogue strophanthidin. Methods: Ventricular myocytes were isolated enzymatically from the guinea pig heart and impaled with conventional microelectrodes to measure action potentials. Cells were voltage clamped and the change in membrane current upon strophanthidin exposure was recorded. Contractile activity was assessed optically as cell shortening. Results: Strophanthidin caused an initial lengthening followed by a progressive shortening of the action potential. The initial lengthening was due to an inhibition of outward Na/K pump current caused by strophanthidin. The subsequent action potential shortening was associated with the progressive activation of a membrane current that reversed at −54.5(SD 7.5) mV, n=8. Since this current was outward over the potential range of the action potential plateau, it participated in causing the action potential shortening with strophanthidin. This component of membrane current was not sensitive to potassium channel blockers, but it was blocked by removing external Ca and applying 5 mM nickel externally. Removal of external Ca inhibits outward current generated by the Ca entry/Na extrusion mode of the Na/Ca exchange, whereas nickel is known to block the Na/Ca exchange. Conclusions: The voltage dependence of the membrane current associated with progressive action potential shortening, and its sensitivity to external Ca and nickel, suggest that it is carried on the Na/Ca exchange. It is proposed that the Na/Ca exchange generates this membrane current in response to the combined rise of intracellular sodium and calcium that occurs with strophanthidin. Theoretical calculations simulating the effect of a combined rise of intracellular sodium and calcium on Na/Ca exchange predict closely the reversal potential and characteristics of the experimentally measured current. The results of this study suggest that a membrane current generated by the Na/Ca exchange makes an important contribution to the action potential shortening that occurs with digitalis compounds. Cardiovascular Research 1993;27:471-481
Defining and Setting National Goals for Cardiovascular Health Promotion and Disease Reduction
Authors: Donald M. Lloyd-Jones, Yuling Hong, Darwin Labarthe, Dariush Mozaffarian, Lawrence J. Appel, Linda Van Horn, Kurt Greenlund, Stephen Daniels, Graham Nichol, Gordon F. Tomaselli, Donna K. Arnett, Gregg C. Fonarow, P. Michael Ho, Michael S. Lauer, Frederick A. Masoudi, Rose Marie Robertson, Véronique Roger, Lee H. Schwamm, Paul Sorlie, Clyde W. Yancy, Wayne D. Rosamond
Journal: Circulation (2010)

This document details the procedures and recommendations of the Goals and Metrics Committee of the Strategic Planning Task Force of the American Heart Association, which developed the 2020 Impact Goals for the organization. The committee was charged with defining a new concept, cardiovascular health , and determining the metrics needed to monitor it over time. Ideal cardiovascular health, a concept well supported in the literature, is defined by the presence of both ideal health behaviors (nonsmoking, body mass index &lt;25 kg/m 2 , physical activity at goal levels, and pursuit of a diet consistent with current guideline recommendations) and ideal health factors (untreated total cholesterol &lt;200 mg/dL, untreated blood pressure &lt;120/&lt;80 mm Hg, and fasting blood glucose &lt;100 mg/dL). Appropriate levels for children are also provided. With the use of levels that span the entire range of the same metrics, cardiovascular health status for the whole population is defined as poor, intermediate, or ideal. These metrics will be monitored to determine the changing prevalence of cardiovascular health status and define achievement of the Impact Goal. In addition, the committee recommends goals for further reductions in cardiovascular disease and stroke mortality. Thus, the committee recommends the following Impact Goals: “By 2020, to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%.” These goals will require new strategic directions for the American Heart Association in its research, clinical, public health, and advocacy programs for cardiovascular health promotion and disease prevention in the next decade and beyond.
RECENT ADVANCES IN CHEMOTHERAPY OF VIRAL DISEASES
Authors: WILLIAM H. PRUSOFF
Journal: Pharmacological Reviews (1967)

Within recent years 2 compounds, idoxuridine (IUdR, 5-iodo-2'-deoxyuridine) and amantadine (Symmetrel), have been approved by the Food and Drug Administration for use in the treatment or prevention of disease caused by viruses in man. The explosive burst of interest in the biochemistry of the reproduction of both RNA and DNA viruses should provide the medicinal chemist with directions for the design of further compounds that have antiviral activity with favorable therapeutic indices. This optimistic hope should be realized within the next decade. The possible if not probable role of viruses in the induction of at least some neoplasms in man is an extremely important direction of present day activities in virology. The prevention of viral infections by vaccines offers great promise of being extended into those diseases at present not under control. However, even if prevention were achieved it would be advantageous to have drugs that could abort those viral infections that do develop. Although these conclusions may appear enthusiastic, they seem justified in view of the rapid developments being made in our understanding of the biochemistry of viruses and their interrelationship with the host cell on a molecular level.
Human eosinophils express transforming growth factor alpha.
Authors: D T Wong, P F Weller, S J Galli, A Elovic, T H Rand, G T Gallagher, T Chiang, M Y Chou, K Matossian, J McBride
Journal: The Journal of Experimental Medicine (1990)

Transforming growth factor alpha (TGF-alpha) is a pleuripotential cytokine with diverse biological effects, including the ability to influence the proliferation of normal cells or neoplastic epithelial cells. Eosinophils are a subset of granulocytes that normally enter the peripheral tissues, particularly those beneath gastrointestinal, respiratory, and urogenital epithelium, where they reside in close proximity to the epithelial elements. In this study, we demonstrate that the great majority of eosinophils infiltrating the interstitial tissues adjacent to two colonic adenocarcinomas and two oral squamous cell carcinomas labeled specifically by in situ hybridization with a 35S-riboprobe for human TGF-alpha (hTGF-alpha). No other identifiable leukocytes in these lesions contained detectable hTGF-alpha mRNA. We also examined leukocytes purified from a patient with the idiopathic hypereosinophilic syndrome. 80% of these eosinophils, but none of the patient's neutrophils or mononuclear cells, were positive for hTGF-alpha mRNA by in situ hybridization, and 55% of these eosinophils were positive by immunohistochemistry with a monoclonal antibody directed against the COOH terminus of the mature hTGF-alpha peptide. Finally, the identification of the purified eosinophil-associated transcript as hTGF-alpha was confirmed by polymerase chain reaction product restriction enzyme analysis followed by Southern blot hybridization. In contrast to eosinophils from the patient with hypereosinophilic syndrome, the peripheral blood eosinophils from only two of seven normal donors had detectable TGF-alpha mRNA and none of these eosinophils contained immunohistochemically detectable TGF-alpha product. Taken together, these findings establish that human eosinophils can express TGF-alpha, but suggest that the expression of TGF-alpha by eosinophils may be under microenvironmental regulation. Demonstration of TGF-alpha production by tissue-infiltrating eosinophils and the eosinophils in the hypereosinophilic syndrome identifies a novel mechanism by which eosinophils might contribute to physiological, immunological, and pathological responses.
TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis
Authors: Dominika E Nanus, Andrew D Filer, Beverly Hughes, Benjamin A Fisher, Peter C Taylor, Paul M Stewart, Christopher D Buckley, Iain McInnes, Mark S Cooper, Karim Raza
Journal: Annals of the Rheumatic Diseases (2014)

To determine the relationship between inflammation and glucocorticoid metabolism in vivo, in a clinical study of patients with inflammatory arthritis treated with anti-TNFα therapy.Urine samples were collected from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as part of a multicentre study assessing responses to infliximab and etanercept. Systemic measures of glucocorticoid metabolism were assessed by gas chromatography/mass spectrometry at weeks 0 (baseline), 4 and 12 after anti-TNFα therapy. Clinical data including DAS28 and C-reactive protein were also collected.Systemic measures of 11β-HSD1 activity in patients with inflammatory arthritis decreased significantly following anti-TNFα therapy in patients with RA and PsA. Additionally, the activity of the glucocorticoid inactivating enzyme 5α-reductase appeared to increase significantly.This study demonstrates, for the first time, that the increased 11β-HSD1 activity seen in patients with inflammatory arthritis is mediated through TNFα. Furthermore, the changes in related glucocorticoid metabolising enzymes suggest that there is a coordinated change in glucocorticoid metabolism which promotes higher tissue glucocorticoid levels.
Pitfalls in diagnosing acute pancreatitis
Authors: J Werner
Journal: Gut (2005)

Pitfalls in diagnosing acute pancreatitisWe thank Jolobe for his letter (Gut 2005;54:1207-8) which mentions the difficulty of establishing the diagnosis of acute pancreatitis in patients with diabetic ketoacidosis.We did not address diagnostic tests and medical intensive care treatment of acute pancreatitis in our article, 1 but reviewed the interventional and surgical treatment strategies in acute pancreatitis.There is no doubt that treatment of acute pancreatitis, including organ failure in its early phase, is solely supportive. 2 Due to improvements in inten- sive care medicine, mortality of severe disease has decreased dramatically over the past decades.However, to treat patient adequately, the correct diagnosis has to be made.Therefore, the first step in the diagnostic process of acute pancreatitis is to think of this disease.According to the latest classification from Atlanta, 3 acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems.From a clinical point of view, acute upper abdominal pain and elevated pancreatic enzyme levels are needed to diagnose acute pancreatitis.As pointed out by Jolobe in his letter, acute pancreatitis is still underdiagnosed under certain clinical conditions, including diabetic ketoacidosis, but also in other clinical situations, such as shock of unknown origin, patients under intensive care treatment, as well as rare causes of the disease.As acute pancreatitis can be associated with diabetic ketoacidosis and the association between these two is a two way cause-and-effect relationship, early imaging of the pancreas is recommended in these patients to establish the correct diagnosis.Our article focused on the surgical and interventional treatment of severe acute pancreatitis.
Lords committee warns of gaps in infection control measures
Authors: L. Eaton
Journal: BMJ (2003)

England has a shortage of appropriately trained experts in identifying infectious diseases, says a report published this week by the House of Lords.

It warns that this is a deficiency that could put the country at risk of failing to notice an outbreak of a potential epidemic, such as the severe acute respiratory syndrome (SARS), and that the country may not be able to cope with a major outbreak of infection.

In its report, Fighting Infection …
Newly Recognized Components of the Renin-Angiotensin System: Potential Roles in Cardiovascular and Renal Regulation
Authors: Robert M. Carey, Helmy M. Siragy
Journal: Endocrine Reviews (2003)

The renin-angiotensin system (RAS) is a coordinated hormonal cascade in the control of cardiovascular, renal, and adrenal function that governs body fluid and electrolyte balance, as well as arterial pressure. The classical RAS consists of a circulating endocrine system in which the principal effector hormone is angiotensin (ANG) II. ANG is produced by the action of renin on angiotensinogen to form ANG I and its subsequent conversion to the biologically active octapeptide by ANG-converting enzyme. ANG II actions are mediated via the ANG type 1 receptor. Here, we discuss recent advances in our understanding of the components and actions of the RAS, including local tissue RASs, a renin receptor, ANG-converting enzyme-2, ANG (1–7), the function of the ANG type 2 receptor, and ANG receptor heterodimerization. The role of the RAS in the regulation of cardiovascular and renal function is reviewed and discussed in light of these newly recognized components.
Phospholamban and troponin I are substrates for protein kinase C in vitro but not in intact beating guinea pig hearts.
Authors: I Edes, E G Kranias
Journal: Circulation Research (1990)

The incorporation of [32P]inorganic phosphate into membranous, myofibrillar, and cytosolic proteins was studied in Langendorff-perfused guinea pig hearts treated with phorbol 12-myristate 13-acetate (PMA) or 1,2-dioctanoylglycerol (D8G), which are potent activators of protein kinase C. Control hearts were perfused with an inactive phorbol ester (4 alpha-phorbol 12,13-didecanoate), which does not cause activation of protein kinase C. To ensure the blockade of different receptor systems, the perfusions were carried out in the presence of prazosin, propranolol, and atropine. Perfusion of hearts with either PMA (4 microM) or D8G (200 microM) was associated with a negative effect on left ventricular inotropy and relaxation. Examination of the 32P incorporation into various fractions revealed that there were no increases in the degree of phosphorylation of phospholamban in sarcoplasmic reticulum, and troponin I and C protein in the myofibrils, although these proteins were found to be substrates for protein kinase C in vitro. However, in the same hearts, there were significant changes in the 32P incorporation into a 28-kDa cytosolic-protein. Examination of the activity levels of protein kinase C in hearts perfused with PMA indicated a redistribution of this activity from the cytosolic to the membrane fraction, suggesting the activation of the enzyme in vivo. These findings indicate that cardiac regulatory phosphoproteins, which may be phosphorylated by protein kinase C in vitro, are not substrates for protein kinase C in beating hearts perfused with phorbol esters or diacylglycerol analogues.