tbuckley/cabot-search huggingface dataset:
Relation between physical exertion and heart rate variability characteristics in professional cyclists during the Tour of Spain
Authors: C P Earnest, R Jurca, T S Church, J L Chicharro, J Hoyos, A Lucia
Journal: British Journal of Sports Medicine (2004)

Background: Continued exposure to prolonged periods of intense exercise may unfavourably alter neuroendocrine, neuromuscular, and cardiovascular function. Objective: To examine the relation between quantifiable levels of exertion (TRIMPS) and resting heart rate (HR) and resting supine heart rate variability (HRV) in professional cyclists during a three week stage race. Method: Eight professional male cyclists (mean (SEM) age 27 (1) years, body mass 65.5 (2.3) kg, and maximum rate of oxygen consumption (V˙ o 2 max ) 75.6 (2.2) ml/kg/min) riding in the 2001 Vuelta a España were examined for resting HR and HRV on the mornings of day 0 (baseline), day 10 (first rest day), and day 17 (second rest day). The rest days followed stages 1–9 and 10–15 respectively. HR was recorded during each race stage, and total HR time was categorised into a modified, three phase TRIMPS schema. These phases were based on standardised physiological laboratory values obtained during previous V˙ o 2 max testing, where HR time in each phase (phase I = light intensity and less than ventilatory threshold (VT; ∼70% V˙ o 2 max ); phase II = moderate intensity between VT and respiratory compensation point (RCP; ∼90% V˙ o 2 max ); phase III = high intensity (&gt;RCP)) was multiplied by exertional factors of 1, 2, and 3 respectively. Results: Multivariate analysis of variance showed that total TRIMPS for race stages 1–9 (2466 (90)) were greater than for stages 10–15 (2055 (65)) (p&lt;0.0002). However, TRIMPS/day were less for stages 1–9 (274 (10)) than for stages 10–15 (343 (11)) (p&lt;0.01). Despite a trend to decline, no difference in supine resting HR was found between day 0 (53.2 (1.8) beats/min), day 10 (49.0 (2.8) beats/min), and day 17 (48.0 (2.6) beats/min) (p = 0.21). Whereas no significant group mean changes in HR or HRV indices were noted during the course of the race, significant inverse Pearson product-moment correlations were observed between all HRV indices relative to total TRIMPS and TRIMPS/day accumulated in race stages 10–15. Total TRIMPS correlated with square root of mean squared differences of successive RR intervals ( r = −0.93; p&lt;0.001), standard deviation of the RR intervals ( r = −0.94; p&lt;0.001), log normalised total power ( r = −0.97; p&lt;0.001), log normalised low frequency power ( r = −0.79; p&lt;0.02), and log normalised high frequency power ( r = −0.94; p&lt;0.001). Conclusion: HRV may be strongly affected by chronic exposure to heavy exertion. Training volume and intensity are necessary to delineate the degree of these alterations.
Different expression of large-conductance calcium-activated K+ channels in human internal mammary and radial arteries
Authors: Yangzhen Shao, Reginald Liew, Bingcai Guan, Philip E.H. Wong, Winston S.N. Shim, Yeowleng Chua, Guowei He
Journal: Cardiovascular Research (2010)

AimsIn this study, we investigated and compared the electrophysiological and molecular properties of large-conductance Ca2+-activated K+ (BKCa) channels between human internal mammary arteries (IMA) and radial arteries (RA).
Crosstalk between Mast Cells and Pancreatic Cancer Cells Contributes to Pancreatic Tumor Progression
Authors: Matthew J. Strouch, Eric C. Cheon, Mohammad R. Salabat, Seth B. Krantz, Elias Gounaris, Laleh G. Melstrom, Surabhi Dangi-Garimella, Edward Wang, Hidayatullah G. Munshi, Khashayarsha Khazaie, David J. Bentrem
Journal: Clinical Cancer Research (2010)

To assess the clinical and pathologic significance of mast cell infiltration in human pancreatic cancer and evaluate crosstalk between mast cells and cancer cells in vitro.Immunohistochemistry for tryptase was done on 53 pancreatic cancer specimens. Mast cell counts were correlated with clinical variables and survival. Serum tryptase activity from patients with cancer was compared with patients with benign pancreatic disease. In vitro, the effect of pancreatic cancer-conditioned medium on mast cell migration was assessed. The effect of conditioned medium from the human mast cell line, LAD-2, on cancer and normal ductal cell proliferation was assessed by thymidine incorporation. Matrigel invasion assays were used to evaluate the effect of mast cell-conditioned medium on cancer cell invasion in the presence and absence of a matrix metalloproteinase inhibitor, GM6001.Mast cell infiltration was significantly increased in pancreatic cancer compared with normal pancreatic tissue (11.4 +/- 6.7 versus 2.0 +/- 1.4, P < 0.001). Increased infiltrating mast cells correlated with higher grade tumors (P < 0.0001) and worse survival. Patients with pancreatic cancer had elevated serum tryptase activity (P < 0.05). In vitro, AsPC1 and PANC-1 cells induced mast cell migration. Mast cell-conditioned medium induced pancreatic cancer cell migration, proliferation, and invasion but had no effect on normal ductal cells. Furthermore, the effect of mast cells on cancer cell invasion was, in large part, matrix metalloproteinase-dependent.Tumor-infiltrating mast cells are associated with worse prognosis in pancreatic cancer. In vitro, the interaction between mast cells and pancreatic cancer cells promotes tumor growth and invasion.
A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate
Authors: S B Cohen
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA). <b>Methods:</b> Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, placebo controlled study. Patients received subcutaneous injections of anakinra 100 mg/day or placebo. They were assessed monthly for 6 months for improvement in signs and symptoms of RA and for adverse events. The primary efficacy measure was the percentage of patients attaining ACR20 response at week 24. <b>Results:</b> Significantly greater proportions of patients treated with anakinra compared with placebo achieved ACR20 (38% <i>v</i> 22%; p&lt;0.001), ACR50 (17% <i>v</i> 8%; p&lt;0.01), and ACR70 (6% <i>v</i> 2%; p&lt;0.05) responses. The response to anakinra was rapid; the proportion of patients with an ACR20 response at the first study assessment (4 weeks) was twice as high with anakinra as with placebo (p&lt;0.005). Clinically meaningful and statistically significant responses were also seen in individual components of the ACR response (for example, Health Assessment Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation rate). Anakinra was well tolerated, with a safety profile, similar to that of placebo with one exception: mild to moderate injection site reactions were more common with anakinra than with placebo (65% <i>v</i> 24%). <b>Conclusions:</b> This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone.
No evidence of an association between mitochondrial DNA variants and osteoarthritis in 7393 cases and 5122 controls
Authors: Gavin Hudson, Kalliope Panoutsopoulou, Ian Wilson, Lorraine Southam, Nigel W Rayner, Nigel Arden, Fraser Birrell, Ian Carluke, Andrew Carr, Kay Chapman, Panos Deloukas, Michael Doherty, Andrew McCaskie, William E R Ollier, Stuart H Ralston, Mike R Reed, Tim D Spector, Ana M Valdes, Gillian A Wallis, J Mark Wilkinson, Eleftheria Zeggini, David C Samuels, John Loughlin, Patrick F Chinnery
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Osteoarthritis (OA) has a complex aetiology with a strong genetic component. Genome-wide association studies implicate several nuclear genes in the aetiology, but a major component of the heritability has yet to be defined at the molecular level. Initial studies implicate maternally inherited variants of mitochondrial DNA (mtDNA) in subgroups of patients with OA based on gender and specific joint involvement, but these findings have not been replicated. <h3>Methods</h3> The authors studied 138 maternally inherited mtDNA variants genotyped in a two cohort genetic association study across a total of 7393 OA cases from the arcOGEN consortium and 5122 controls genotyped in the Wellcome Trust Case Control consortium 2 study. <h3>Results</h3> Following data quality control we examined 48 mtDNA variants that were common in cohort 1 and cohort 2, and found no association with OA. None of the phenotypic subgroups previously associated with mtDNA haplogroups were associated in this study. <h3>Conclusions</h3> We were not able to replicate previously published findings in the largest mtDNA association study to date. The evidence linking OA to mtDNA is not compelling at present.
Clinical review articles.
Authors: R. B. Haynes
Journal: BMJ (1992)

An admirable example of enhancing adherence by offering establishment of regional multidisciplinary pain management a synthesis that allows for the patients' pain beliefs is offered units there are very few in the United Kingdom.by Feinmann et al.9They sidestep the psychological-physical Chronic orofacial pain can be a disturbing problem for divide neatly by offering an explanation of pain that empha-patient and doctor.If attention is paid to reconciling the sises the role of muscular tension in its genesis, then prescribe patient's experiences and expectations of treatment with a the antidepressant dothiepin hydrochloride, emphasising its proposed course of treatment the outcome can be successful muscle relaxing properties.and the prognosis good.These difficult patients can then Antidepressants are the most successful and widely evalu-become a rewarding group to treat.ated drugs used to treat these types of "psychogenic" facial STEPHEN HUNTER pain, and their benefits seem to be independent of any ConsultantinPsychologicalMedicine, antidepressant action.There is no good evidence to support Gwent NP6 I XQ the use of one drug over another, or of particular dosage regimens, although most trials have used doses over the 1 Bonica JJ.Pain research therapy.Past and current status and future needs.In: Ng LKY, Bonica JJ, * * r l r * * t-* r
SELECTED PERSONAL AND FAMILY DATA ON 400 PSYCHIATRIC INPATIENTS
Authors: IAN GREGORY
Journal: American Journal of Psychiatry (1962)

The type of data analyzed in the present study may provide evidence concerning the validity of clinical diagnosis in psychiatry, a differential contribution of hereditary and environmental factors in the etiology of specific diagnoses, and association between objective criteria of environmental influence and various diagnostic categories. Selected personal and family data were recorded soon after admission on 400 out of 449 consecutive psychiatric patients admitted to the University of Minnesota Hospitals and assigned to the care of residents under the supervision of a staff psychiatrist. The data on 30 patients (with diagnoses of organic brain syndromes, mental deficiency, or observation only) were discarded, and the data on the remaining 370 patients were divided into 7 major categories for purposes of analysis. Primary characteristics of patients (particularly age, sex, education and marital status) showed a significant lack of homogeneity among the 7 diagnostic groups, giving some support to the validity of clinical diagnosis in psychiatry. At least it is evident that these diagnostic groups differ from each other significantly with respect to these characteristics, though it remains questionable to what extent they differ in their manifestations, etiology or response to treatment. Most of the selected characteristics involving parents and sibships failed to show deviations from homogeneity among the 7 diagnostic groups, and hence provided little evidence concerning the influence of specific etiological factors in the development of specific diagnostic syndromes. In patients with a history of parental suicide or admission to mental hospital, certain diagnoses were represented more or less frequently than expected on a random basis. However, this association between patient diagnosis and parental psychopathology may be related to either genetic or environmental factors. The increased frequencies of certain diagnoses among patients with intervals of less than two years between themselves and their preceding or following siblings are suggestive of environmental influences in the etiology of the diagnostic groups involved, but the findings in this relatively small and heterogeneous sample must be regarded as very tentative.
Mapping and Ablation of Ventricular Fibrillation Associated With Long-QT and Brugada Syndromes
Authors: Michel Haïssaguerre, Fabrice Extramiana, Mélèze Hocini, Bruno Cauchemez, Pierre Jaïs, Jose Angel Cabrera, Geronimo Farre, Antoine Leenhardt, Prashanthan Sanders, Christophe Scavée, Li-Fern Hsu, Rukshen Weerasooriya, Dipen C. Shah, Robert Frank, Philippe Maury, Marc Delay, Stéphane Garrigue, Jacques Clémenty
Journal: Circulation (2003)

Background— The long-QT and Brugada syndromes are important substrates of malignant ventricular arrhythmia. The feasibility of mapping and ablation of ventricular arrhythmias in these conditions has not been reported. Methods and Results— Seven patients (4 men; age, 38±7 years; 4 with long-QT and 3 with Brugada syndrome) with episodes of ventricular fibrillation or polymorphic ventricular tachycardia and frequent isolated or repetitive premature beats were studied. These premature beats were observed to trigger ventricular arrhythmias and were localized by mapping the earliest endocardial activity. In 4 patients, premature beats originated from the peripheral right (1 Brugada) or left (3 long-QT) Purkinje conducting system and were associated with variable Purkinje-to-muscle conduction times (30 to 110 ms). In the remaining 3 patients, premature beats originated from the right ventricular outflow tract, being 25 to 40 ms ahead of the QRS. The accuracy of mapping was confirmed by acute elimination of premature beats after 12±6 minutes of radiofrequency applications. During a follow-up of 17±17 months using ambulatory monitoring and defibrillator memory interrogation, no patients had recurrence of symptomatic ventricular arrhythmia but 1 had persistent premature beats. Conclusion— Triggers from the Purkinje arborization or the right ventricular outflow tract have a crucial role in initiating ventricular fibrillation associated with the long-QT and Brugada syndromes. These can be eliminated by focal radiofrequency ablation.
Outcome of Burkholderia cepacia colonisation in an adult cystic fibrosis centre
Authors: M J Ledson
Journal: Thorax (2002)

Background: Colonisation with <i>Burkholderia cepacia</i> is a poor prognostic indicator in subjects with cystic fibrosis (CF), but outcome prediction is impossible since patients are colonised by different strains with differing pathogenicity. The clinical course of a large cohort of CF patients colonised with UK epidemic (ET12) <i>B cepacia</i> was followed for 5 years and compared with that of the remaining patients in the clinic. Methods: Pulmonary function, nutritional state, and lung pathogen colonisation were recorded for 5 years before December 1997 or death for all 107 patients who had attended the Liverpool adult CF clinic since 1993. For each patient a time line from study entry to date of death or 1997 was constructed. In 1993 potential risk factors including age and sex were subjected to Cox proportional hazards analysis using the end point of mortality as the outcome variable. The analysis was supplemented by time varying covariables that described the change in FEV<sub>1</sub>, BMI, and colonisation status across time, and the excess risk associated with <i>B cepacia</i> colonisation was calculated. Subsequently, in those patients who died between 1993 and 1997, predictive factors for death were compared within groups using complete 5 year data. Results: Thirty seven patients had been colonised by epidemic <i>B cepacia</i> and these patients had four times the mortality of the remainder (p&lt;0.01). In 1993 univariate predictors of mortality were age (alive 19.6 (0.64) <i>v</i> dead 23.8 (1.44); p&lt;0.005) and baseline FEV<sub>1</sub> (alive 68.6 (2.5)% predicted <i>v</i> dead 43.2 (4.8)%; p&lt;0.001) with a trend for BMI (p=0.07). However, following time varying covariate Cox proportional hazards analysis, only lower FEV<sub>1</sub> (hazards ratio 1.1, 95% confidence limits 1.06 to 1.14; p&lt;0.001) and colonisation with <i>B cepacia</i> (hazards ratio 7.92, confidence limits 2.65 to 23.69; p&lt;0.001) were identified as significant factors for death. Surviving <i>B cepacia</i> patients had similar initial lung function to the remaining surviving patients but had an accelerated loss of lung function over the study period (colonised –1.9% predicted per year <i>v</i> non-colonised –0.3% predicted per year; p&lt;0.05). Deceased patients colonised with <i>B cepacia</i> had better spirometric results than the remaining deceased patients 5 years before death (p&lt;0.05) but lost lung function at a greater rate than non-colonised patients (colonised –6.2% predicted per year <i>v</i> non-colonised –1.9% predicted per year; p&lt;0.05). Conclusions: This study confirms the excess mortality associated with epidemic <i>B cepacia</i> colonisation and shows that those with poor spirometric values are at the greatest risk.
Reference point-dependent tradeoffs in intertemporal decision making
Authors: X. T. Wang, Jeffrey S. Simons
Journal: Behavioral and Brain Sciences (2005)

We agree with Ainslie's general approach to intertemporal choices and self-control. However, we argue that a concept of “will” is superfluous in explaining tradeoffs between SS (smaller and sooner) and LL (larger and later) rewards in a framework of temporal goal setting and goal aggregation. We provide an alternative framework of reference point-dependent tradeoffs between SS and LL options.
Atrial Sources of Reactive Oxygen Species Vary With the Duration and Substrate of Atrial Fibrillation
Authors: Svetlana N. Reilly, Raja Jayaram, Keshav Nahar, Charalambos Antoniades, Sander Verheule, Keith M. Channon, Nicholas J. Alp, Ulrich Schotten, Barbara Casadei
Journal: Circulation (2011)

An altered nitric oxide-redox balance has been implicated in the pathogenesis of atrial fibrillation (AF). Statins inhibit NOX2-NADPH oxidases and prevent postoperative AF but are less effective in AF secondary prevention; the mechanisms underlying these findings are poorly understood.By using goat models of pacing-induced AF or of atrial structural remodeling secondary to atrioventricular block and right atrial samples from 130 patients undergoing cardiac surgery, we found that the mechanisms responsible for the NO-redox imbalance differ between atria and with the duration and substrate of AF. Rac1 and NADPH oxidase activity and the protein level of NOX2 and p22phox were significantly increased in the left atrium of goats after 2 weeks of AF and in patients who developed postoperative AF in the absence of differences in leukocytes infiltration. Conversely, in the presence of longstanding AF or atrioventricular block, uncoupled nitric oxide synthase activity (secondary to reduced BH4 content and/or increased arginase activity) and mitochondrial oxidases accounted for the biatrial increase in reactive oxygen species. Atorvastatin caused a mevalonate-reversible inhibition of Rac1 and NOX2-NADPH oxidase activity in right atrial samples from patients who developed postoperative AF, but it did not affect reactive oxygen species, nitric oxide synthase uncoupling, or BH4 in patients with permanent AF.Upregulation of atrial NADPH oxidases is an early but transient event in the natural history of AF. Changes in the sources of reactive oxygen species with atrial remodeling may explain why statins are effective in the primary prevention of AF but not in its management.
Results of European post-marketing surveillance of bosentan in pulmonary hypertension
Authors: M. Humbert, E. S. Segal, D. G. Kiely, J. Carlsen, B. Schwierin, M. M. Hoeper
Journal: European Respiratory Journal (2007)

After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile. A novel, prospective, internet-based PMS was designed, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events and elevated aminotransferases. Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. In total, 4,623 patients were naïve to treatment; of these, 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 (3.2%) bosentan-naïve patients. Safety results were consistent across subgroups and aetiologies. The novel post-marketing surveillance captured targeted safety data ("potential safety signals") from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials and provide important additional information on the safety profile of bosentan.