tbuckley/cabot-search huggingface dataset:
Acetazolamide and Breathing
Authors: LUC J. TEPPEMA, ALBERT DAHAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Improvement of blood gases with the carbonic anhydrase inhibitor acetazolamide in some patients with chronic obstructive pulmonary disease (COPD) is believed to result from an effect on the ventilatory control system. Carbonic anhydrase is ubiquitously present within the body, particularly in tissues involved in the control of breathing. Because low inhibitor concentrations are sufficient to block the enzyme in many tissues, it is of interest to document the effect of clinical doses of acetazolamide on the CO(2) sensitivities of the peripheral and central chemoreflex loops. In this study we measured the effect of chronic acetazolamide (250 mg by way of mouth, every 8 h during 3 days) on the dynamic ventilatory response to step changes in end-tidal PCO(2) in nine healthy volunteers. Data were analyzed using a two-compartment model comprising a fast peripheral and slow central compartment, enabling us to separate drug effects on the peripheral and central chemoreflex loops, respectively. Compared with placebo, acetazolamide did not change the CO(2) sensitivities and time constants of both chemoreflex loops. However, mean (+/- SD) resting ventilation increased from 12.22 +/- 2.41 to 14.01 +/- 1.85 L. min(-1), resulting in a decrease in end-tidal PCO(2) from 40.0 +/- 4.7 to 33.3 +/- 3.5 mm Hg. Base excess decreased from -0.08 +/- 1.20 to -7.48 +/- 2.07 mmol. L(-1), indicating metabolic acidosis and explaining a leftward shift of the CO(2) response curve by 7.3 mm Hg. Possible clinical implications of these results are discussed.
Human in vitro fertilisation and embryo replacement and transfer
Authors: S J G Spencer
Journal: BMJ (1983)

Presenilins are ubiquitous, intramembrane proteins that function in Alzheimer9s disease (AD) as the catalytic component of the γ-secretase complex. Familial AD mutations in presenilin are known to exacerbate lysosomal pathology. Hence, we sought to elucidate the function endogenous, wild-type presenilins play in autophagy-mediated protein degradation. We report the finding that genetic deletion or knockdown of presenilins alters many autophagy-related proteins demonstrating a buildup of autophagosomes, indicative of dysfunction in the system. Presenilin-deficient cells inefficiently clear long-lived proteins and fail to build up autophagosomes when challenged with lysosomal inhibitors. Our studies further show that γ-secretase inhibitors do not adversely impact autophagy, indicating that the role of presenilins in autophagy is independent of γ-secretase activity. Based on our findings, we conclude that endogenous, wild-type presenilins are necessary for proper protein degradation through the autophagosome–lysosome system by functioning at the lysosomal level. The role of presenilins in autophagy has many implications for its function in neurological diseases such as AD.
Relation between monophasic action potential duration, ST segment elevation, and regional myocardial blood flow after coronary occlusion in the pig
Authors: R. O KINGABY, M. J LAB, A. W G COLE, T N. PALMER
Journal: Cardiovascular Research (1986)

There is mounting interest in the use of the monophasic action potential for electrophysiological investigation of regional myocardial ischaemia. There is, however, no systematic study of the relation between the changes in monophasic action potential and regional myocardial blood flow. In this study monophasic action potential and, for comparison, epicardial electrograms were recorded by suction electrode at 14 selected sites on the anterior surface of the normal left ventricle of the intact pig heart in situ (n = 16). The monophasic action potential duration varied across the left ventricle; it was shortest close to the left anterior descending coronary artery, increased laterally across the left ventricle, and was longer at the apex than at the base. This variation was independent of regional myocardial blood flow (measured with radiolabelled microspheres). After coronary occlusion, in nine of these pigs monophasic action potential duration significantly decreased in proportion to the reduction in regional myocardial blood flow. The ST segment of the epicardial electrogram was elevated in relation to the reduction in regional myocardial blood flow but correlated less well. The reduction in regional myocardial blood flow of approximately 50% produced maximal ST elevation. The monophasic action potential could be recorded from some sites within the border zone for up to 5 h but could not be recorded from the centre of an ischaemic zone. With ischaemic episodes of this duration there was, however, a return to baseline of the elevated ST segment for all sites within the compromised region. Monophasic action potential duration, unlike epicardial electrogram ST elevation, discriminates between central ischaemic and non-ischaemic and ischaemic sites on either side of the zone with a reduced blood flow. The results suggest that monophasic action potential duration measured by suction electrode may be a simple and reliable index of transmural-epicardial myocardial ischaemia in experimental studies and in surgery.
Radioembolization for hepatocellular carcinoma
Authors: Bruno Sangro, Mercedes Iñarrairaegui, Jose I. Bilbao
Journal: Journal of Hepatology (2011)

Radioembolization is a form of brachytherapy in which intra-arterially injected (90)Y-loaded microspheres serve as sources for internal radiation purposes. It produces average disease control rates above 80% and is usually very well tolerated. Main complications do not result from the microembolic effect, even in patients with portal vein occlusion, but rather from an excessive irradiation of non-target tissues including the liver. All the evidence that support the use of radioembolization in HCC is based on retrospective series or non-controlled prospective studies. However, reliable data can be obtained from the literature, particularly since the recent publication of large series accounting for nearly 700 patients. When compared to the standard of care for the intermediate and advanced stages (transarterial embolization and sorafenib), radioembolization consistently provides similar survival rates. Two indications seem particularly appealing in the boundaries of these stages for first-line radioembolization. First, the treatment of patients straddling between the intermediate and advanced stages (intermediate patients with bulky or bilobar disease that are considered poor candidates for TACE, and advanced patients with solitary tumors invading a segmental or lobar branch of the portal vein). Second, the treatment of patients that are slightly above the criteria for resection, ablation or transplantation, for which downstaging could open the door for a radical approach. Radioembolization can also be used to treat patients progressing to TACE or sorafenib. With a number of clinical trials underway, the available evidence shows that it adds a significant value to the therapeutic weaponry against HCC of tertiary care centers dealing with this major cancer problem.
Imaging Cycling Tumor Hypoxia
Authors: Shingo Matsumoto, Hironobu Yasui, James B. Mitchell, Murali C. Krishna
Journal: Cancer Research (2010)

Cycling hypoxia is now a well-recognized phenomenon in animal and human solid tumors. Cycling hypoxia can exist more than 100-μm distances from a microvessel, and some of these regions have been shown to exist adjacent to normal tissue. Fluctuations in pO(2) of approximately 20 mm Hg can occur with periodicities of minutes to hours and even days. These fluctuations have been attributed to changes in erythrocyte flux, perfusion, and also development of newer vascular networks. Cycling hypoxia has been shown to induce the expression of hypoxia-inducible transcription factor-1α (HIF-1α) and also confer tumor cells and tumor vascular endothelial cells with enhanced prosurvival pathways, making tumors less responsive to radiation and chemotherapy. Imaging of cycling hypoxia in tumors can provide capabilities to help plan appropriate treatment, by taking into account the magnitude and frequency of fluctuations and also their locations adjacent to normal tissue. Electron paramagnetic resonance imaging (EPRI) provides the ability to distinguish chronic and cycling hypoxic regions and has the required spatial and temporal resolutions to provide quantitative maps of tumor pO(2). EPRI can serve as a valuable tool in examining tumor pO(2) longitudinally in response to treatment and in an experimentally chosen time window to spatially map fluctuations in pO(2) noninvasively in animal models of implanted or orthotopic tumors, with a potential for human applications.
VISUALIZATION OF FLOW DYNAMICS FROM PULMONARY VEINS TO LEFT ATRIUM AND LEFT VENTRICLE USING PHASE-RESOLVED 3D CINE PHASE CONTRAST MRI (4D-FLOW)
Authors: Takeji Saito, Kenichiro Suwa, Makoto Sano, Mamoru Nobuhara, Masao Saotome, Tsuyoshi Urushida, Hideki Katoh, Hiroshi Satoh, Yasuo Takehara, Marcus Alley, Harumi Sakahara, Hideharu Hayashi
Journal: Journal of the American College of Cardiology (2013)
Bronchoalveolar lavage for evaluation and management of scleroderma disease of the lung.
Authors: J Behr, C Vogelmeier, T Beinert, M Meurer, F Krombach, G König, G Fruhmann
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Fibrosing alveolitis (FA) is a frequent and often fatal complication of systemic sclerosis (SSC). Alveolar inflammation has been recognized as a primary event in the pulmonary manifestation of SSC. To evaluate the significance of the alveolitis in SSC, we performed bronchoalveolar lavage (BAL) and correlated the generated data with changes in lung function over time. Seventy nine SSC patients with pulmonary involvement were followed for 56.8 +/- 3.1 wk (mean +/- SEM) with a repeat lung function test at the end of the follow-up period. During follow-up, 38 patients were treated with a systemic immunosuppressive regimen. For evaluation, patients were assigned to two groups according to whether their BAL cell differential was normal (inactive BAL) or abnormal (active BAL: i.e., polymorphonuclear leukocytes > 5% and/or lymphocytes > 15%). Active BAL was associated with more severe lung function impairment than was inactive BAL, and patients with active BAL deteriorated during follow-up if untreated. In contrast, treated patients with active BAL stabilized or improved. In summary, active alveolitis as characterized by BAL is associated with progressive pulmonary disease in SSC patients, and a significant positive effect of immunosuppressive therapy on the course of pulmonary disease was observed in patients with active BAL.
Socioeconomic differences in mortality among diabetic people in Finland: five year follow up
Authors: S. V P Koskinen, T. P Martelin, T. Valkonen
Journal: BMJ (1996)

To compare socioeconomic differences in mortality (by cause of death) among diabetic people with those in the rest of the population.Five year follow up of mortality in the population of Finland, comparing people with diabetes and those without diabetes.Finland.All residents of Finland aged 30 to 74 included in the 1980 census. Subjects were classified as diabetic (230,000 person years) or other (12,400,000 person years) according to whether they were exempted from charges for medication for diabetes. During 1981-5 there were 114,058 deaths, of which 11,215 were in people with diabetes.Age standardised mortality by sex, social class, and cause of death for the diabetic and non-diabetic populations.No significant social class differences in mortality were found among women with diabetes. Among diabetic men there was a slight increasing trend in mortality from the upper while collar group to the unskilled blue collar workers but it was much less steep than that of non-diabetic men.Among people with diabetes in Finland the quality of treatment and compliance with treatment probably do not vary by socioeconomic status. Health education for diabetic people seems to be effective in all socioeconomic strata; in people from the lower strata this leads to greater changes because their health behavior was originally less good.
P182 Adenosine potentiates human mast cell fibrinolytic activity
Authors: M. J. Sereda, P. Bradding, C. Vial
Journal: Thorax (2010)

We investigated whether adenosine, a potent contributor to the regulation of pulmonary function, can modulate human lung mast cell (HLMC) fibrinolytic activity. Tissue plasminogen activator (tPA) activity and tPA transcript expression levels from a human mast cell line (HMC-1) and HLMC were monitored following adenosine application. Adenosine potentiated mast cell tPA activity and tPA gene expression in a dose-dependent manner. Adenosine effects were abolished in the presence of adenosine deaminase. HMC-1 cells predominantly expressed adenosine A<sub>2A</sub> and A<sub>2B</sub> receptor transcripts (A<sub>2A</sub>&gt;&gt;A<sub>2B</sub>&gt;A<sub>3</sub>&gt;&gt;A<sub>1</sub>). In addition to A<sub>2A</sub> and A<sub>2B</sub>, A<sub>3</sub> receptor transcripts were also abundantly found in HLMC (A<sub>2A</sub>&gt;&gt;A<sub>2B</sub>&gt;&gt;A<sub>3</sub>&gt;&gt;A<sub>1</sub>). Pharmacological and signalling studies suggest that the A<sub>2A</sub> receptor is the major subtype accounting for adenosine-induced mast cell tPA activity. Finally, the supernatant from HMC-1 cells treated with adenosine (24h) significantly increased fibrin clot lysis, while ZM241385, an A<sub>2A</sub> receptor antagonist, abolished this effect. This study provides the first data to demonstrate the potentiating effect of adenosine on mast cell tPA activity and fibrin clot lysis.
Minimum price for alcohol proves hard to swallow in Scotland
Authors: B. Christie
Journal: BMJ (2009)

Health campaigners have reacted angrily to the decision by opposition politicians in Scotland to block moves to raise the price of cheap alcoholic drinks.

Legislation proposed by the Scottish government would have made it the first country in northern Europe to introduce minimum pricing for alcohol. A price of 40 p (€0.44; $0.65) a unit would almost triple the cost of cheap ciders and increase the price of low cost beers and spirits, the drinks favoured by problem drinkers.

Scotland has the eighth highest alcohol consumption in the world. One in 20 …
Current Review of Complementary Medicine
Authors: Brent A. Bauer
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes16 November 1999Current Review of Complementary MedicineBrent A. Bauer, MDBrent A. Bauer, MDMayo Clinic, Rochester, Minnesota. (Bauer)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-10-199911160-00038 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Micozzi MS, ed. 167 pages. Philadelphia: Current Medicine; 1999. $49.95. ISBN 1573401293. Order phone 800-543-1918.Field of medicine: Complementary and alternative medicine (CAM).Format: Hardcover book.Audience: Physicians, residents, and students seeking additional perspective on the growing field of CAM.Purpose: To “ … provide clinicians with valid information … to allow a sound basis for making clinical decisions” about CAM therapies.Content: Four chapters deal with herbal therapy. Single chapters discuss acupuncture, chiropractic, therapeutic touch, chelation therapy, and homeopathy. Four chapters cover use of CAM to treat food allergy, HIV, fibromyalgia, chronic fatigue syndrome, and coronary artery disease. Business ... Author, Article, and Disclosure InformationAffiliations: Mayo Clinic, Rochester, Minnesota. (Bauer) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 November 1999Volume 131, Issue 10Page: 800KeywordsComplementary and alternative medicineFood allergiesForecastingHIVHerbal medicineHomeopathyMortalitySoftware toolsStable coronary artery diseaseTouch ePublished: 15 August 2000 Issue Published: 16 November 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The role of opioid substitution treatment in reducing HIV transmission
Authors: L. R. Gowing
Journal: BMJ (2012)

Risks for drug users and the wider community are substantially reduced

Prevention of HIV is one of the more persuasive public health arguments in favour of opioid substitution treatment. However, until now, there has been no quantitative estimate of the extent to which this treatment reduces the transmission of HIV. This knowledge gap has been filled by the findings of a linked systematic review by MacArthur and colleagues (doi:10.1136/bmj.e5945).1 This analysis of data from nine studies that included 819 incident HIV infections over 23 608 person years of follow-up found that treatment with methadone was associated with a 54% reduction in the risk of HIV infection among people who inject drugs. 

An earlier systematic review found that opioid substitution treatment with methadone or buprenorphine is associated with reductions in behaviours associated with a high risk of HIV transmission,2 but owing to methodological limitations, overall estimates of the extent of reduction of these risk behaviours were not calculated. Individual studies were consistent in their findings of reductions of illicit opioid use (ranging from 32% to 69%), injecting drug use (20-60%), and sharing of injecting equipment (25-86%). Treatment …
Abstract 1745: Foxp3 expression and prognosis in early stage non-small cell lung cancer
Authors: Hiroyuki Tao
Journal: Cancer Research (2010)

Abstract Foxp3 is a transcription factor that specifically characterizes regulatory T cells (Tregs). Increased number of tumor-infiltrating Tregs has been reported to be related to poor prognosis. Recently, it has been demonstrated that cancer cells also can express foxp3 and its expression level correlates with unfavorable prognosis in several types of malignant tumors. In non-small cell lung cancer (NSCLC), prognostic impact of foxp3 expressing cancer cells is not yet determined. We examined foxp3 expression in resected NSCLC and investigated its association with recurrence. Methods: Foxp3 expressing cancer cells were detected by immunohistochemical staining from surgically removed specimens of the 59 patients with NSCLC that were pathologically diagnosed with Stage Ia or Ib. Prognostic value of foxp3 was evaluated by Kaplan-Meier analysis and log-rank test. Results: Male/female: 41/19, p-stage Ia/Ib: 39/20, squamous(sq)/adeno(ad)/adenosquamous(adsq)/large and LCNEC: 16/36/3/4. Foxp3 positive cancer cells were observed in 17 of 59 patients (28.8%, male/female: 9/8, p-stage Ia/Ib: 10/7, sq/ad/adsq/large and LCNEC: 2/12/1/2). Of the 59 patients examined, recurrent tumors were seen in 12 within two years. Of the 12 patients who experienced recurrence, foxp3 expression in cancer cells were detected in 4 (33.3%). Of the 47 patients without relapse within five years, foxp3 positive tumor cells were observed in 13 (27.7%). Kaplan-Meier analysis and log-rank test showed no significant difference between the presence or absence of the foxp3 positive cancer cells both in overall and relapse free survival. Conclusions: In our study, foxp3 expressing tumor cells were seen in 28.8% of the patients with node-negative NSCLC. Prognositic value of foxp3 positive cancer cells in p-Stage I NSCLC was not determined. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1745.
Exposure to Cigarette Smoke and Cervical Cancer
Authors: Edith A. Zang
Journal: JAMA (1989)

To the Editor.—  We would like to comment on the article by Slattery et al 1 entitled Cigarette Smoking and Exposure to Passive Smoke Are Risk Factors for Cervical Cancer.  In case-control studies there is always the danger of overmatching or undermatching in selection of control subjects. In this report, there clearly is undermatching of control patients with regard to important risk factors including sexual activity, religious background, and education. For example, 52% of control subjects vs only 10% of case subjects reported having fewer than two sexual partners; 75% of control subjects but only 49% of case subjects were high school graduates; and 58% of control subjects vs 18% of case subjects were frequent churchgoers. Since the previously mentioned risk factors are correlated highly with one another as well as with active and passive smoking, the risk estimates relating smoking and cervical cancer may be subject to substantial bias
Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus
Authors: Scott J. Rodig, Jingwei Cheng, Jacek Wardzala, Andrew DoRosario, Jessica J. Scanlon, Alvaro C. Laga, Alejandro Martinez-Fernandez, Justine A. Barletta, Andrew M. Bellizzi, Subhashini Sadasivam, Dustin T. Holloway, Dylan J. Cooper, Thomas S. Kupper, Linda C. Wang, James A. DeCaprio
Journal: Journal of Clinical Investigation (2012)

A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC) specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host cell chromosomes of MCC tumors and expresses small T antigen and truncated large T antigen. Previous studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tumors. We sought to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecting large T antigen by immunohistochemistry. In addition, we expanded the repertoire of quantitative PCR primers specific for MCPyV to improve the detection of viral DNA in MCC. Here we report that a novel monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%) unique MCC tumors. PCR analysis specifically detected viral DNA in all 60 unique MCC tumors tested. We also detected inactivating point substitution mutations of TP53 in the two MCC specimens that lacked large T antigen expression and in only 1 of 56 tumors positive for large T antigen. These results indicate that MCPyV is present in MCC tumors more frequently than previously reported and that mutations in TP53 tend to occur in MCC tumors that fail to express MCPyV large T antigen.
Structure-function studies and molecular regulation of the growth factor activatable sodium-hydrogen exchanger (NHE-1)
Authors: L. Counillon, J. Pouyssegur
Journal: Cardiovascular Research (1995)

Journal Article Structure-function studies and molecular regulation of the growth factor activatable sodium-hydrogen exchanger (NHE-1) Get access Laurent Counillon, Laurent Counillon * Centre de Biochimie-CNRS, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice, France *Correspondence to Dr Counillon. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jacques Pouysségur Jacques Pouysségur Centre de Biochimie-CNRS, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 2, February 1995, Pages 147–154, https://doi.org/10.1016/S0008-6363(96)88562-2 Published: 01 February 1995 Article history Received: 30 March 1994 Accepted: 04 October 1994 Published: 01 February 1995
Echocardiographic Evaluation of Pulmonary Artery Pressure in Patients With Heart Failure
Authors: Dimitrios Farmakis, Athanasios Aessopos
Journal: Journal of the American College of Cardiology (2012)

We read with great interest the report by Bursi et al. ([1][1]) on the prognostic value of pulmonary pressure in heart failure (HF). The investigators used Doppler-determined pulmonary artery systolic pressure (PASP), which requires an estimation of right atrial pressure by the diameter and