bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dehydroepiandrosterone reverses chronic hypoxia/reoxygenation-induced right ventricular dysfunction in rats
Authors: Dumas de La Roque Eric , Bellance Nadège , Rossignol Rodrigue , Begueret Hugues , Billaud Marie , Dos Santos Pierre , Ducret Thomas , Marthan Roger , Dahan Diana , Ramos-Barbón David , Amor-Carro Óscar , Savineau Jean-Pierre , Fayon Michael 
Published: April 2012

Dehydroepiandrosterone (DHEA) prevents chronic hypoxia-induced pulmonary hypertension and associated right ventricle dysfunction in rats. In this animal model, reoxygenation following hypoxia reverses pulmonary hypertension but not right ventricle dysfunction. We thus studied the effect of DHEA on the right ventricle after reoxygenation,i.e.after a normoxic recovery phase secondary to chronic hypoxia in rats.Right ventricle function was assessedin vivoby Doppler echocardiography andin vitroby the isolated perfused heart technique in three groups of animals: control, recovery (21 days of hypoxia followed by 21 days of normoxia) and recovery DHEA (30 mg·kg−1every 2 days during the recovery phase). Right ventricle tissue was assessed by optical and electron microscopy.DHEA abolished right ventricle diastolic dysfunction, as the echographic E wave remained close to that of controls (mean±sd76.5±2.4 and 79.7±1.7 cm·s−1, respectively), whereas it was diminished to 40.3±3.7 in the recovery group. DHEA also abolished right ventricle systolic dysfunction, as shown by the inhibition of the increase in the slope of the pressure–volume curve in isolated heart. The DHEA effect was related to cardiac myocytes proliferation.In conclusion, DHEA prevents right ventricle dysfunction in this animal model by preventing cardiomyocyte alteration.
Expressed wishes and incidence of euthanasia in advanced lung cancer patients
Authors: Pardon Koen , Deschepper Reginald , Vander Stichele Robert , Bernheim Jan L. , Mortier Freddy , Schallier Denis , Germonpré Paul , Galdermans Daniella , Van Kerckhoven Willem , Deliens Luc 
Published: April 2012

This study explores expressed wishes and requests for euthanasia (i.e.administration of lethal drugs at the explicit request of the patient), and incidence of end-of-life decisions with possible life-shortening effects (ELDs) in advanced lung cancer patients in Flanders, Belgium.We performed a prospective, longitudinal, observational study of a consecutive sample of advanced lung cancer patients and selected those who died within 18 months of diagnosis. Immediately after death, the pulmonologist/oncologist and general practitioner (GP) of the patient filled in a questionnaire. Information was available for 105 out of 115 deaths.According to the specialist or GP, one in five patients had expressed a wish for euthanasia; and three in four of these had made an explicit and repeated request. One in two of these received euthanasia. Of the patients who had expressed a wish for euthanasia but had not made an explicit and repeated request, none received euthanasia. Patients with a palliative treatment goal at inclusion were more likely to receive euthanasia. Death was preceded by an ELD in 62.9% of patients.To conclude, advanced lung cancer patients who expressed a euthanasia wish were often determined. Euthanasia was performed significantly more among patients whose treatment goal after diagnosis was exclusively palliative.
Pulmonary hypertension associated with benfluorex exposure
Authors: Savale Laurent , Chaumais Marie-Camille , Cottin Vincent , Bergot Emmanuel , Frachon Irène , Prevot Grégoire , Pison Christophe , Dromer Claire , Poubeau Patrice , Lamblin Nicolas , Habib Gilbert , Reynaud-Gaubert Martine , Bourdin Arnaud , Sanchez Olivier , Tubert-Bitter Pascale , Jaïs Xavier , Montani David , Sitbon Olivier , Simonneau Gérald , Humbert Marc 
Published: April 2012

Benfluorex was marketed in France until 2009, despite its similar pharmacological properties with fenfluramine and its derivatives known to be a cause of pulmonary arterial hypertension (PAH).The aim of this study is to report clinical and haemodynamic characteristics for patients suffering from pulmonary hypertension (PH) associated with benfluorex exposure that had been identified by the French PAH Network.85 cases of PH associated with benfluorex exposure were identified by the French PAH Network from June 1999 to March 2011. Of these, 70 patients had confirmed pre-capillary PH. The median duration of exposure was 30 months, with a median of 108 months between start of exposure and diagnosis of the pulmonary vascular disease. 33% of all patients also had prior exposure to fenfluramine or dexfenfluramine, and an additional risk factor for PH was identified in 20 (30%) out of 70 patients with pre-capillary PH. A quarter of patients in this current series showed coexisting PH and mild-to-moderate cardiac valve involvement.The results of our study, together with the accumulated data regarding the known toxic effects of fenfluramine and dexfenfluramine, strongly suggest that benfluorex exposure is a potent trigger for PAH.
Pulse transit time as a measure of respiratory effort under noninvasive ventilation
Authors: Contal Olivier , Carnevale Claudio , Borel Jean-Christian , Sabil AbdelKébir , Tamisier Renaud , Lévy Patrick , Janssens Jean-Paul , Pépin Jean-Louis 
Published: April 2012

Among the respiratory events that may occur during nocturnal noninvasive ventilation (NIV), differentiating between central and obstructive events requires appropriate indicators of respiratory effort. The aim of the present study was to assess pulse transit time (PTT) as an indicator of respiratory effort under NIV in comparison with oesophageal pressure (Poes).During wakefulness, PTT was compared toPoesduring spontaneous breathing and under NIV with or without induced leaks in 11 healthy individuals. In addition, the contribution of PTTversus Poesto differentiation of central from obstructive respiratory events occurring under NIV during sleep was evaluated in 10 patients with obesity hypoventilation syndrome (OHS).From spontaneous breathing to NIV without leaks, respiratory effort decreased significantly whereas, with increasing level of leaks, there was a significant increase in respiratory effort. Changes in PTT accurately reflected changes inPoes. In OHS patients during nocturnal NIV, intraclass correlation coefficients betweenPoesand PTT were 0.970 for total number of events and 0.970 for percentage of central events.PTT accurately reflects the unloading of respiratory muscles induced by NIV and the increase in respiratory effort during leaks. PTT during sleep is also useful to differentiate central from obstructive respiratory events occurring under NIV.
Aα-Val360: a marker of neutrophil elastase and COPD disease activity
Authors: Carter Richard I. , Ungurs Michael J. , Mumford Richard A. , Stockley Robert A. 
Published: April 2012

Forced expiratory volume in 1 s is currently the most widely used marker of chronic obstructive pulmonary disease (COPD) severity; however, it is a poor surrogate of the emphysematous component and the underlying pathophysiological mechanism, and therefore new markers are urgently needed. Neutrophil elastase (NE) is likely to play a key pathophysiological role in COPD and the current study explores a marker of NE activity as a potential indicator of COPD disease activity.Aα-Val360was measured in 81 subjects with a clinical diagnosis of COPD, both in the stable state and at presentation with an acute exacerbation, and comparisons were made using lung function tests and computed tomography imaging. The relationship of Aα-Val360with disease progression was also assessed in 40 of the subjects over a 4-yr period.Baseline Aα-Val360related to physiological and radiological markers of disease severity, was higher at presentation with an acute exacerbation than in the stable state and (at least partly) related to disease progression over the subsequent 4 yrs.We demonstrate that Aα-Val360is a marker of cross-sectional COPD disease severity and possibly disease progression, and represents a new concept of specific biomarkers. This study therefore reports the firstin vivodata to support the pathophysiological role of NE in COPD.
Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries
Authors: Nagaraj Chandran , Tang Bi , Bálint Zoltán , Wygrecka Malgorzata , Hrzenjak Andelko , Kwapiszewska Grazyna , Stacher Elvira , Lindenmann Joerg , Weir E. Kenneth , Olschewski Horst , Olschewski Andrea 
Published: April 2012

The potassium channel TWIK-related acid sensitive potassium (TASK)-1 channel, together with other potassium channels, controls the low resting tone of pulmonary arteries. The Src family tyrosine kinase (SrcTK) may control potassium channel function in human pulmonary artery smooth muscle cells (hPASMCs) in response to changes in oxygen tension and the clinical use of a SrcTK inhibitor has resulted in partly reversible pulmonary hypertension.This study aimed to determine the role of SrcTK in hypoxia-induced inhibition of potassium channels in hPASMCs.We show that SrcTK is co-localised with the TASK-1 channel. Inhibition of SrcTK decreases potassium current density and results in considerable depolarisation, while activation of SrcTK increases potassium current in patch-clamp recordings. Moderate hypoxia and the SrcTK inhibitor decrease the tyrosine phosphorylation state of the TASK-1 channel. Hypoxia also decreases the level of phospho-SrcTK (tyr419) and reduces the co-localisation of the TASK-1 channel and phospho-SrcTK. Corresponding to this, hypoxia reduces TASK-1 currents before but not after SrcTK inhibition and, in the isolated perfused mouse lung, SrcTK inhibitors increase pulmonary arterial pressure.We propose that the SrcTK is a crucial factor controlling potassium channels, acting as a cofactor for setting a negative resting membrane potential in hPASMCs and a low resting pulmonary vascular tone.
Cell-based analysis of Chikungunya virus E1 protein in membrane fusion
Authors: Kuo Szu-Cheng , Chen Ying-Ju , Wang Yu-Ming , Tsui Pei-Yi , Kuo Ming-Der , Wu Tzong-Yuan , Lo Szecheng J 
Published: April 2012

Abstract

Background
Chikungunya fever is a pandemic disease caused by the mosquito-borne Chikungunya virus (CHIKV). E1 glycoprotein mediation of viral membrane fusion during CHIKV infection is a crucial step in the release of viral genome into the host cytoplasm for replication. How the E1 structure determines membrane fusion and whether other CHIKV structural proteins participate in E1 fusion activity remain largely unexplored.

Methods
A bicistronic baculovirus expression system to produce recombinant baculoviruses for cell-based assay was used. Sf21 insect cells infected by recombinant baculoviruses bearing wild type or single-amino-acid substitution of CHIKV E1 and EGFP (enhanced green fluorescence protein) were employed to investigate the roles of four E1 amino acid residues (G91, V178, A226, and H230) in membrane fusion activity.

Results
Western blot analysis revealed that the E1 expression level and surface features in wild type and mutant substituted cells were similar. However, cell fusion assay found that those cells infected by CHIKV E1-H230A mutant baculovirus showed little fusion activity, and those bearing CHIKV E1-G91D mutant completely lost the ability to induce cell-cell fusion. Cells infected by recombinant baculoviruses of CHIKV E1-A226V and E1-V178A mutants exhibited the same membrane fusion capability as wild type. Although the E1 expression level of cells bearing monomeric-E1-based constructs (expressing E1 only) was greater than that of cells bearing 26S-based constructs (expressing all structural proteins), the sizes of syncytial cells induced by infection of baculoviruses containing 26S-based constructs were larger than those from infections having monomeric-E1 constructs, suggesting that other viral structure proteins participate or regulate E1 fusion activity. Furthermore, membrane fusion in cells infected by baculovirus bearing the A226V mutation constructs exhibited increased cholesterol-dependences and lower pH thresholds. Cells bearing the V178A mutation exhibited a slight decrease in cholesterol-dependence and a higher-pH threshold for fusion.

Conclusions
Cells expressing amino acid substitutions of conserved protein E1 residues of E1-G91 and E1-H230 lost most of the CHIKV E1-mediated membrane fusion activity. Cells expressing mutations of less-conserved amino acids, E1-V178A and E1-A226V, retained membrane fusion activity to levels similar to those expressing wild type E1, but their fusion properties of pH threshold and cholesterol dependence were slightly altered.
Factors contributing to therapeutic effects evaluated in acupuncture clinical trials
Authors: Shi Guang-Xia , Yang Xiao-Min , Liu Cun-Zhi , Wang Lin-Peng 
Published: April 2012

Abstract
Acupuncture treatment has been widely used for many conditions, while results of the increasing numbers of randomized trials and systematic reviews remain controversial. Acupuncture is a complex intervention of both specific and non-specific factors associated with therapeutic benefit. Apart from needle insertion, issues such as needling sensation, psychological factors, acupoint specificity, acupuncture manipulation, and needle duration also have relevant influences on the therapeutic effects of acupuncture. Taking these factors into consideration would have considerable implications for the design and interpretation of clinical trials.
Ultra-low dose dual-source high-pitch computed tomography of the paranasal sinus: diagnostic sensitivity and radiation dose
Authors: Schulz Boris , Potente Stefan , Zangos Stefan , Friedrichs Ingke , Bauer Ralf W , Kerl Matthias , Vogl Thomas J , Mack Martin M 
Published: April 2012

Background Today's gold standard for diagnostic imaging of inflammatory diseases of the paranasal sinus is computed tomography (CT). Purpose To evaluate diagnostic sensitivity and radiation dose of an ultra-low dose dual-source CT technique. Material and Methods Paranasal sinuses of 14 cadaveric heads were independently evaluated by two readers using a modern dual-source CT with lowest reasonable dosage in high-pitch mode (100 kV, 10 mAs, collimation 0.6 mm, pitch value 3.0). Additionally the head part of an anthropomorphic Alderson-Rando phantom was equipped with thermoluminiscent detectors to measure radiation exposure to the eye lenses and thyroid gland. Results Diagnostic accuracy regarding sinusoidal fluid, nasal septum deviation, and mucosal swelling was 100%. Mastoid fluid was detected in 76% and 92%, respectively. In the phantom study, average measured eye lens dosage was 0.64 mGy; radiation exposure of the thyroid gland was 0.085 mGy. Conclusion Regarding evaluation of inflammatory diseases of the paranasal sinus this study indicates sufficient accuracy of the proposed CT protocol at a very low dosage level.
Vitamin D deficiency is not associated with early stages of thyroid autoimmunity
Authors: Effraimidis Grigoris , Badenhoop Klaus , Tijssen Jan G P , Wiersinga Wilmar M 
Published: April 2012

ContextVitamin D deficiency has been identified as a risk factor for a number of autoimmune diseases including type 1 diabetes and multiple sclerosis.ObjectiveWe hypothesized that low levels of vitamin D are related to the early stages of autoimmune thyroid disease (AITD).DesignTwo case–control studies were performed. In the cross-sectional study A, euthyroid subjects with genetic susceptibility for AITD but without thyroid antibodies were compared with controls. Cases were subjects from the Amsterdam AITD cohort (euthyroid women who had first- or second-degree relatives with overt AITD) who at baseline had normal TSH and no thyroid antibodies; controls were healthy women examined at the same period. In the longitudinal study B, subjects who developed de novo thyroid peroxidase antibody (TPO-Ab) were compared with those who did not. Cases and controls were subjects from the Amsterdam AITD cohort who at baseline had normal TSH and no thyroid antibodies and during follow-up developed TPO-Ab (cases) or remained without thyroid antibodies (controls). Controls in both studies were matched for age, BMI, smoking status, estrogen use, month of blood sampling, and in study B for the duration of follow-up.ResultsSerum 25(OH)D levels were as follows: study A: 21.0±7.9 vs 18.0±6.4 ng/ml (78 cases vs 78 controls, P=0.01); study B: baseline, 22.6±10.3 vs 23.4±9.1; follow-up 21.6±9.2 vs 21.2±9.3 ng/ml (67 cases vs 67 controls, NS).ConclusionsEarly stages of thyroid autoimmunity (in study A genetic susceptibility and in study B development of TPO-Ab) are not associated with low vitamin D levels.
Prognostic Role of Serum Parathyroid Hormone Levels in Advanced Prostate Cancer Patients Undergoing Zoledronic Acid Administration
Authors: Berruti Alfredo , Cook Richard , Saad Fred , Buttigliero Consuelo , Lipton Allan , Tampellini Marco , Lee Ker-Ai , Coleman Robert E. , Smith Matthew R. 
Published: April 2012

Abstract

Background.
Secondary hyperparathyroidism is frequent in prostate cancer patients with bone metastases, and this condition is worsened by the administration of potent bisphosphonates. Serum parathyroid hormone (PTH) elevation can impair the efficacy of these drugs in terms of survival.

Methods.
The prognostic role of elevated serum PTH levels at baseline and after 3 months of zoledronic acid administration was assessed prospectively in 643 bone metastatic prostate cancer patients enrolled in a prospective randomized, placebo-controlled study.

Results.
On multivariate analysis, after adjusting for major prognostic factors and bone turnover markers, elevated baseline serum PTH level was negatively associated with overall survival (hazard ratio [HR], 1.448; 95% confidence interval [CI], 1.045–2.006; p &lt; .03) in zoledronic acid–treated patients but not in placebo-treated patients. In patients with normal baseline PTH levels, there was a trend but insignificant association between zoledronic acid administration and a better survival outcome than with placebo (HR, 0.81; 95% CI, 0.65–1.01; p = .065), whereas a trend in the opposite direction was observed in patients with elevated PTH levels (HR, 1.45; 95% CI, 0.87–2.39; p = .151); interaction test, p = .040. Elevated serum PTH level after 3 months of zoledronic acid treatment was not significantly associated with survival outcome.

Conclusions.
Secondary hyperparathyroidism has a negative prognostic impact in metastatic prostate cancer patients undergoing zoledronic acid administration. Counteracting elevated PTH levels by adequate doses of vitamin D may improve the efficacy of this drug.
Renal Replacement Therapy in the Elderly Population
Authors: Berger Joseph R. , Hedayati S. Susan 
Published: April 2012

Summary
ESRD has become an important problem for elderly patients. The segment of the ESRD population age 65 years or older has grown considerably, and this growth is expected to accelerate in coming years. Nephrologists caring for the elderly with advanced kidney disease will encounter patients with comorbid conditions common in younger patients, as well as physical, psychological, and social challenges that occur with increased frequency in the aging population. These challenging factors must be addressed to help inform decisions regarding the option to initiate dialysis, the choice of dialysis modality, whether to pursue kidney transplantation, and end-of-life care. This article will highlight some common problems encountered by elderly patients with ESRD and review data on the clinical outcomes of elderly patients treated with different modalities of dialysis, outcomes of kidney transplantation in the elderly, and nondialytic management of CKD stage 5.
CKD and Coronary Collateral Supply in Individuals Undergoing Coronary Angiography after Myocardial Infarction
Authors: Charytan David M. , Stern Noam M. , Mauri Laura 
Published: April 2012

Summary

Background and objectives
CKD patients have high mortality risk after myocardial infarction (MI). An adequate supply of coronary collaterals to the culprit vessel responsible for MI is associated with reduced risks of death and complications. Whether a diminished supply of collaterals contributes to the high risk in CKD patients is uncertain.

Design, setting, participants, & measurements
Quantitative coronary angiography was performed in a consecutive series of individuals with (n=58) and without (n=165) CKD (estimated GFR <60 ml/min per 1.73 m2) who underwent coronary angiography at the time of MI. Collateral supply was analyzed and candidate predictors were assessed in patient-level and individual artery-level models using logistic regression and ordered categorical regression, respectively.

Results
There were no significant differences in collateral supply among 58 CKD patients and 165 individuals with preserved renal function. Culprit artery collaterals were present in 25.0% of CKD patients compared with 27.2% of individuals with preserved renal function (P=0.76). The odds of having an adequate supply of culprit vessel collaterals were also not significantly different in individuals with and without CKD, respectively. CKD patients were 2.22-fold more likely to have visible collaterals to the nonculprit vessels in unadjusted analyses. The difference was not significant after correction for percent stenosis and comorbid factors.

Conclusions
Our results do not support an independent association between CKD and diminished collateral supply to either the culprit or nonculprit vessels in MI. Additional studies are warranted to better define associations between myocardial capillary supply, collateral supply, and the full range of human CKD.
Vasopressin, Copeptin, and Renal Concentrating Capacity in Patients with Autosomal Dominant Polycystic Kidney Disease without Renal Impairment
Authors: Zittema Debbie , Boertien Wendy E. , van Beek André P. , Dullaart Robin P.F. , Franssen Casper F.M. , de Jong Paul E. , Meijer Esther , Gansevoort Ron T. 
Published: April 2012

Summary

Background and objectives
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary renal disease, characterized by cyst formation in the kidneys leading to end stage kidney failure. It is clinically acknowledged that ADPKD patients have impaired urine concentrating capacity, but the mechanism behind this observation is unknown.

Design, setting, participants, & measurements
Fifteen ADPKD patients (estimated GFR ≥60 ml/min per 1.73 m2) and 15 age- and sex-matched healthy controls underwent a standard prolonged water deprivation test in which urine and plasma osmolality, vasopressin, and copeptin were measured. The effect of a synthetic vasopressin analog (desmopressin) injected at the moment of maximal urine concentrating capacity was also studied.

Results
After 14 hours of water deprivation, ADPKD patients tended to have higher plasma osmolality (P=0.07) and significantly higher vasopressin and copeptin levels (both P<0.05), whereas urine osmolality was similar in ADPKD patients and controls (710 versus 742 mOsmol/kg; P=0.61). Maximal urine concentrating capacity was lower in ADPKD patients (758 versus 915 mOsmol/kg in controls; P<0.001). At maximal urine concentrating capacity, plasma osmolality, vasopressin, and copeptin levels were significantly higher in ADPKD patients. The median increase in urine osmolality after desmopressin administration in ADPKD patients was less than in healthy controls.

Conclusions
Already early in their disease, ADPKD patients have impaired maximal urine concentrating capacity brought out upon dehydration, with no evidence of impaired hypothalamic response. To maintain fluid balance, vasopressin concentration increases, which is hypothesized to play a role in ADPKD disease progression.