tbuckley/cabot-search huggingface dataset:
Dual Pathways of Carbon Monoxide–Mediated Vasoregulation
Authors: Brian D. Lamon, Frank F. Zhang, Nitin Puri, Sergey V. Brodsky, Michael S. Goligorsky, Alberto Nasjletti
Journal: Circulation Research (2009)

Rationale : Vascular tissues produce carbon monoxide (CO) via HO-dependent and HO-independent mechanisms; the former in tandem with biliverdin and iron and the latter as a lone product. CO has been shown to function as both a vasoconstrictor and vasodilator; however, factors that dictate the vasoregulatory phenotype of this gas are unknown. Objective : We investigated whether CO-mediated vasoconstriction is mechanistically linked to enhanced reactive oxygen species production that masks vasodilatory pathways. Methods and Results : Sprague–Dawley rat interlobar and interlobular arteries were examined in terms of superoxide (O 2 ·− ) generation and vascular reactivity in the absence and presence of antioxidants. Both authentic CO and the CO-releasing molecule (CORM)-3 constricted renal arteries and increased O 2 ·− production in a dose-dependent manner. The antioxidants tempol, ebselen, and deferoxamine inhibited CO-induced O 2 ·− production and converted CO from constrictor to dilator. CO-induced O 2 ·− generation was found to involve the activity of multiple oxidases including nitric oxide synthase, NADPH oxidase, xanthine oxidase, and complex IV of the mitochondrial electron chain. Furthermore, inhibition of these enzymes converted CO from constrictor to dilator. Similarly, biliverdin and bilirubin inhibited CO-induced O 2 ·− production and vasoconstriction, allowing for a vasodilatory response to CO to be expressed. CO-induced vasoconstriction was dependent on a non-thromboxane agonist of the thromboxane receptor, whereas vasodilatory mechanisms of CO relied on the activation of soluble guanylate cyclase and calcium-gated potassium channels. Conclusions : CO-induced vasoconstriction involves the generation of reactive oxygen species, which, when negated, allows for the expression of vasodilatory pathways which are masked by the primary oxidative stress response to this gas.
Eosinophil Lipid Bodies: Specific, Inducible Intracellular Sites for Enhanced Eicosanoid Formation
Authors: Patricia T. Bozza, Wengui Yu, John F. Penrose, Ellen S. Morgan, Ann M. Dvorak, Peter F. Weller
Journal: The Journal of Experimental Medicine (1997)

The specific intracellular sites at which enzymes act to generate arachidonate-derived eicosanoid mediators of inflammation are uncertain. We evaluated the formation and function of cytoplasmic lipid bodies. Lipid body formation in eosinophils was a rapidly (&amp;lt;1 h) inducible response which was platelet-activating factor (PAF) receptor–mediated, involved signaling through protein kinase C, and required new protein synthesis. In intact and enucleated eosinophils, the PAF-induced increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. All principal eosinophil eicosanoid-forming enzymes, 5-lipoxygenase, leukotriene C4 synthase, and cyclooxygenase, were immunolocalized to native as well as newly induced lipid bodies in intact and enucleated eosinophils. Thus, lipid bodies are structurally distinct, inducible, nonnuclear sites for enhanced synthesis of paracrine eicosanoid mediators of inflammation.
Evidence of Linkage to Chromosome 9q22.33 in Colorectal Cancer Kindreds from the United Kingdom
Authors: Zoe E. Kemp, Luis G. Carvajal-Carmona, Ella Barclay, Margaret Gorman, Lynn Martin, Wendy Wood, Andrew Rowan, Claire Donohue, Sarah Spain, Emma Jaeger, D. Gareth Evans, Eamonn R. Maher, Timothy Bishop, Huw Thomas, Richard Houlston, Ian Tomlinson
Journal: Cancer Research (2006)

Abstract About 30% of all colorectal cancers are thought to have a genetic basis and the known predisposing genes can only account for a small fraction of cases. A previous report suggested that a colorectal cancer candidate gene, explaining at least 20% of colorectal cancer cases with family history, was located within a 25 cM region on chromosome 9q22.2-q31.3. We typed 16 polymorphic markers encompassing the region of putative linkage in 57 colorectal tumor families from the United Kingdom. Known Mendelian syndromes had been excluded. We found suggestive evidence of linkage, as positive parametric (HLOD = 1.23) and nonparametric (NPL = 1.21, P = 0.11) LOD scores were obtained by analysis of the whole family set. Enrichment for cases with a priori genetic etiology by analyzing families with at least one person affected at &amp;lt;45 years of age (n = 39 families) gave a maximum multipoint NPL score of 2.65 (P = 0.007). In this group, significant NPL scores &amp;gt;1.67 (P &amp;lt; 0.05) were found in a 6.5 cM region between D9S1851 and D9S277. With a more stringent threshold (NPL&amp;gt;2.4, P &amp;lt; 0.01), the linked region was 1.7 cM between D9S971 and D9S272/D9S173. Exclusion from the analysis of kindreds with a phenotype of multiple polyposis also found evidence of linkage in the same region (NPL = 2.47 at close to D9S277, P = 0.009). The type I transforming growth factor-β receptor, a prime candidate gene, was excluded as a cause of disease. The results presented here further support the existence of a colorectal cancer susceptibility gene on chromosome 9q and refine its likely location. (Cancer Res 2006; 66(10): 5003-6)
Endovascular vs. Open Repair of Abdominal Aortic Aneurysms in the Medicare Population
Authors: Marc L. Schermerhorn, A. James O'Malley, Ami Jhaveri, Philip Cotterill, Frank Pomposelli, Bruce E. Landon
Journal: New England Journal of Medicine (2008)

Randomized trials have shown reductions in perioperative mortality and morbidity with endovascular repair of abdominal aortic aneurysm, as compared with open surgical repair. Longer-term survival rates, however, were similar for the two procedures. There are currently no long-term, population-based data from the comparison of these strategies.
POPULATION BIOLOGY OF HIV-1 INFECTION: Viral and CD4<sup>+</sup>T Cell Demographics and Dynamics in Lymphatic Tissues
Authors: A. T. Haase
Journal: Annual Review of Immunology (1999)

▪ Abstract Human immunodeficiency virus-1 (HIV-1) is usually transmitted through sexual contact and in the very early stages of infection establishes a persistent infection in lymphatic tissues (LT). Virus is produced and stored at this site in a dynamic process that slowly depletes the immune system of CD4 + T cells, setting the stage for AIDS. In this review, I describe the changes in viral and CD4 + T cell populations in LT over the course of infection and after treatment. I present recent evidence that productively infected CD4 + T cells play an important role in establishing persistent infection from the onset, and that the LT are the major reservoir where virus is produced and stored on follicular dendritic cells (FDCs). I discuss the methods used to define the size of viral and CD4 + T cell populations in LT and the nature of virus-host cell interactions in vivo. These experimental approaches have identified populations of latently and chronically infected cells in which virus can elude host defenses, perpetuate infection, and escape eradication by highly active antiretroviral treatment (HAART). I discuss the dramatic impact of HAART on suppressing virus production, reducing the pool of stored virus, and restoring CD4 + T cell populations. I discuss the contributions of thymopoiesis and other renewal mechanisms, lymphatic homeostasis and trafficking to these changes in CD4 + T cell populations in LT, and conclude with a model of immune depletion and repopulation based on the limited regenerative capacity of the adult and the uncompensated losses of productively infected cells that treatment stems. The prediction of this model is that immune regeneration will be slow, variable, and partial. It is nonetheless encouraging to know that even in late stages of infection, control of active replication of HIV-1 provides an opportunity for the immune system to recover from the injuries inflicted by infection.
Pathophysiology of increased nuchal translucency: a review of the literature
Authors: M. C. Haak
Journal: Human Reproduction Update (2003)

First-trimester nuchal translucency (NT) measurement is a widely used technique to determine the risk of fetal aneuploidy. The aim of this review was to explore the different hypotheses on the aetiology of increased NT. Using a computerized database (PubMed), articles on the aetiology of first-trimester NT were retrieved. Furthermore, the cited references of the studied articles were used to find additional articles. Based on ultrasonographic and post-mortem morphological studies, the findings in increased NT fetuses are described and classified into three categories. First, an association between increased NT and cardiac abnormalities, combined with abnormal ductus venosus flow velocities, is found, leading to the theory that cardiac failure causes NT enlargement. Second, various types of abnormalities are found in the extracellular matrix of the nuchal skin of fetuses with increased NT. Third, abnormal lymphatic development is demonstrated in fetuses with increased NT. In conclusion, many hypotheses on NT enlargement are based on associations and speculations. This report provides an overview of the different theories and an attempt to fit the different associations and findings into a single hypothesis of abnormal embryological development.
Journal: War of words over Iraq
Authors: R. Coombes
Journal: BMJ (2003)

Should medical journals have a role in the debate over military intervention?

The possibility of a war against Iraq currently has some medical editors at each other's throats. What is at issue, however, is not so much the potential conflict itself, but whether or not medical journals should contribute to the debate over military intervention.

This war of words has broken out among members of the World Association of Medical Editors or WAME (http://www.wame.org/), which is open to the editors of peer reviewed medical journals worldwide. One of WAME's founding principles was that member journals should inform readers “about non-clinical aspects of medicine and public health including … political issues.” This does not mean, however, that editors agree on how far the potentially devastating humanitarian consequences of an Iraqi war is their business.

Mark Graczynski, editor of the Medical Science Monitor , an online journal produced from New York, is one of many contributors to the debate raging on WAME's online discussion forum. …
Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis
Authors: P. Valent, L. Escribano, S. Broesby‐Olsen, K. Hartmann, C. Grattan, K. Brockow, M. Niedoszytko, B. Nedoszytko, J. N. G. Oude Elberink, T. Kristensen, J. H. Butterfield, M. Triggiani, I. Alvarez‐Twose, A. Reiter, W. R. Sperr, K. Sotlar, S. Yavuz, H. C. Kluin‐Nelemans, O. Hermine, D. Radia, J. J. van Doormaal, J. Gotlib, A. Orfao, F. Siebenhaar, L. B. Schwartz, M. Castells, M. Maurer, H.‐P. Horny, C. Akin, D. D. Metcalfe, M. Arock
Journal: Allergy (2014)

Abstract Mastocytosis is an emerging differential diagnosis in patients with more or less specific mediator‐related symptoms. In some of these patients, typical skin lesions are found and the diagnosis of mastocytosis can be established. In other cases, however, skin lesions are absent, which represents a diagnostic challenge. In the light of this unmet need, we developed a diagnostic algorithm for patients with suspected mastocytosis. In adult patients with typical lesions of mastocytosis in the skin, a bone marrow ( BM ) biopsy should be considered, regardless of the basal serum tryptase concentration. In adults without skin lesions who suffer from mediator‐related or other typical symptoms, the basal tryptase level is an important parameter. In those with a slightly increased tryptase level, additional investigations, including a sensitive KIT mutation analysis of blood leucocytes or measurement of urinary histamine metabolites, may be helpful. In adult patients in whom (i) KIT D816V is detected and/or (ii) the basal serum tryptase level is clearly increased (&gt;25–30 ng/ml) and/or (iii) other clinical or laboratory features suggest the presence of ‘occult’ mastocytosis or another haematologic neoplasm, a BM investigation is recommended. In the absence of KIT D816V and other signs or symptoms of mastocytosis or another haematopoietic disease, no BM investigation is required, but the clinical course and tryptase levels are monitored in the follow‐up. In paediatric patients, a BM investigation is usually not required, even if the tryptase level is increased. Although validation is required, it can be expected that the algorithm proposed herein will facilitate the management of patients with suspected mastocytosis and help avoid unnecessary referrals and investigations.
The open circuit nitrogen washout technique for measuring the lung volume in infants: methodological aspects
Authors: M. G Morris
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Lung volume measurement by nitrogen washout is widely used in infants, though a lack of accuracy and changes of calibration over time have been reported. The potential sources of error were explored in order to increase the accuracy and reliability of the technique. <h3>METHODS</h3> A commercial system for nitrogen washout and a 0.5 litre calibrating syringe as a lung model were used to perform over 2000 in vitro washouts, including simulated rapid breathing, shallow breathing, periodic breathing, sighs, and brief apnoeas. A constant 10 l/min bias flow of oxygen and extended equipment warming times were employed. A collapsible breathing bag was incorporated into the washout circuit. Following a single two point calibration, known air volumes from 42 ml to 492 ml were measured by nitrogen washout over a 14 hour period. The flow waveform in the nitrogen mixing chamber during a washout in vitro, with and without the breathing bag in the circuit, was also studied. <h3>RESULTS</h3> The mean coefficient of variation of all volumes was 0.66%. The mean difference between measured and known volumes was 0.30 ml (95% confidence interval (CI) –0.18 to 0.79). This difference was not statistically significant (p = 0.22). The mean percentage error was –0.1% (range –0.47% to 0.46%). Nitrogen calibration remained stable for 14 hours. Without the breathing bag flow transients were frequent in the mixing chamber during in vitro washout. <h3>CONCLUSIONS</h3> This technique increases the accuracy in vitro and the precision in vivo of volume measurement by nitrogen washout. Sources of potential errors including baseline drifting and inadequate equipment warming times were identified. The breathing bag acted as a buffer reservoir, preventing large swings in flows within the nitrogen mixing chamber during washouts, and should be an integral component of the nitrogen washout circuit.
Development of a shuttle walking test of disability in patients with chronic airways obstruction.
Authors: S J Singh, M D Morgan, S Scott, D Walters, A E Hardman
Journal: Thorax (1992)

The aim was to develop a standardised and externally paced field walking test, incorporating an incremental and progressive structure, to assess functional capacity in patients with chronic airways obstruction.The usefulness of two different shuttle walking test protocols was examined in two separate groups of patients. The initial 10 level protocol (group A, n = 10) and a subsequent, modified, 12 level protocol (group B, n = 10) differed in the number of increments and in the speeds of walking. Patients performed three shuttle walking tests one week apart. Then the performance of patients (group C, n = 15) in the six minute walking test was compared with that in the second (modified) shuttle walking test protocol. Heart rate was recorded during all the exercise tests with a short range telemetry device.The 12 level modified protocol provided a measure of functional capacity in patients with a wide range of disability and was reproducible after just one practice walk; the mean difference between trial 2 v 3 was -2.0 (95% CI -21.9 to 17.9) m. There was a significant relation between the distance walked in the six minute walking test and the shuttle walking test (rho = 0.68) but the six minute walking test appeared to overestimate the extent of disability in some patients. The shuttle test provoked a graded cardiovascular response not evident in the six minute test. Moreover, the maximal heart rates attained were significantly higher for the shuttle walking test than for the six minute test.The shuttle walking test constitutes a standardised incremental field walking test that provokes a symptom limited maximal performance. It provides an objective measurement of disability and allows direct comparison of patients' performance.
Oral appliances for the management of snoring and obstructive sleep apnoea
Authors: L. S. Bennett, R. J. Davies, J. R. Stradling
Journal: Thorax (1998)

BACKGROUND: Although oral appliances are effective in some patients with obstructive sleep apnoea (OSA), they are not universally effective. A novel anterior mandibular positioner (AMP) has been developed with an adjustable hinge that allows progressive advancement of the mandible. The objective of this prospective crossover study was to compare efficacy, side effects, patient compliance, and preference between AMP and nasal continuous positive airway pressure (nCPAP) in patients with symptomatic mild to moderate OSA. METHODS: Twenty four patients of mean (SD) age 44.0 (10.6) years were recruited with a mean (SD) body mass index of 32.0 (8.2) kg/m2, Epworth sleepiness score 10.7 (3.4), and apnoea/hypopnoea index 26.8 (11.9)/hour. There was a two week wash-in and a two week wash-out period and two treatment periods (AMP and nCPAP) each of four months. Efficacy, side effects, compliance, and preference were evaluated by a questionnaire and home sleep monitoring. RESULTS: One patient dropped out early in the study and three refused to cross over so treatment results are presented on the remaining 20 patients. The apnoea/hypopnoea index (AHI) was lower with nasal CPAP 4.2 (2.2)/hour than with the AMP 13.6 (14.5)/hour (p &lt; 0.01). Eleven of the 20 patients (55%) who used the AMP were treatment successes (reduction of AHI to &lt; 10/hour and relief of symptoms), one (5%) was a compliance failure (unable or unwilling to use the treatment), and eight (40%) were treatment failures (failure to reduce AHI to &lt; 10/hour and/or failure to relieve symptoms). Fourteen of the 20 patients (70%) who used nCPAP were treatment successes, six (30%) were compliance failures, and there were no treatment failures. There was greater patient satisfaction with the AMP (p &lt; 0.01) than with nCPAP but no difference in reported side effects or compliance. CONCLUSIONS: AMP is an effective treatment in some patients with mild to moderate OSA and is associated with greater patient satisfaction than nCPAP.
Metastatic Colon Cancer, Version 3.2013
Authors: Al B. Benson, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Marwan G. Fakih, Moon J. Fenton, Charles S. Fuchs, Jean L. Grem, Steven Hunt, Ahmed Kamel, Lucille A. Leong, Edward Lin, Kilian Salerno May, Mary F. Mulcahy, Kate Murphy, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, William Small, Constantinos T. Sofocleous, Alan P. Venook, Christopher G. Willett, Kristina M. Gregory, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2013)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions surrounding metastatic colorectal cancer for the 2013 update of the guidelines. Importantly, changes were made to the continuum of care for patients with advanced or metastatic disease, including new drugs and an additional line of therapy.
Prevalence and course of sleep-disordered breathing in acute decompensated heart failure
Authors: Olaf Oldenburg, Jens Spießhöfer, Henrik Fox, Birgit Wellmann, Kristina Basic, Dieter Horstkotte
Journal: European Respiratory Journal (2014)

The prevalence of sleep-disordered breathing (SDB) in acute decompensated HF (ADHF) and course during re-compensation is unknown and has been analyzed in this prospective study.  Consecutive ADHF patients with clinical signs (fluid overload) and symptoms (NYHA class III or IV) of decompensated HF underwent cardiorespiratory polygraphy (PG) to determine the apnea-hypopnea index (AHI), number of oxygen desaturations (ODI) and the percentage of recording time spent with oxygen saturation   A total of 107 patients were screened, 2 denied study participation. Of those included into the study, 11 withdrew their consent before PG study or PG recordings failed due to technical issues, in 2 patients HF deteriorated within hours, not allowing any PG study. In remaining 92 patients a PG study was performed revealing a SDB prevalence of 95.7%; AHI was 33.0 ± 21.7/h, ODI 30.3 ± 19.5/h, apnea index (AI) 15.0 ± 18.7/h, oAI 3.6 ± 8.5/h, cAI 10.1 ± 15.0/h, and mAI 1.4 ± 6.4/h. Mean oxygen saturation was 91.2 ± 3.3% and minimum 77.3 ± 9.3%, respectively. In 74 patients a second PG study was performed 2 days later, revealing no significant change in the number of respiratory events.  SDB is highly prevalent in hospitalized ADHF patients. About 50% of respiratory events are apneas with the vast majority being of central origin. This prevalence and the distribution of respiratory events did not change during 2 days of intensive cardiac care with a significant decrease in body weight and a trend towards improved BNP concentrations.
Ultrasound stimulation restores impaired neovascularization-related capacities of human circulating angiogenic cells
Authors: Yasuyuki Toyama, Ken-ichiro Sasaki, Katsuro Tachibana, Takafumi Ueno, Hidemi Kajimoto, Shinji Yokoyama, Masanori Ohtsuka, Hiroshi Koiwaya, Takaharu Nakayoshi, Yoshiaki Mitsutake, Hidetoshi Chibana, Naoki Itaya, Tsutomu Imaizumi
Journal: Cardiovascular Research (2012)

AimsUnsatisfactory effects of therapeutic angiogenesis in critical limb ischaemia may be ascribed to use of circulating angiogenic cells (CACs) derived from atherosclerotic patients with impaired neovascularization-related capacities. We tested whether ultrasound cell stimulation can restore the impaired capacities.