共查询到20条相似文献,搜索用时 46 毫秒
1.
Zoltan Nemeth Attila Cziraki Sandor Szabados Bernadett Biri Sandor Keki Akos Koller 《PloS one》2015,10(8)
Background
Pericardial fluid (PF) contains several biologically active substances, which may provide information regarding the cardiac conditions. Nitric oxide (NO) has been implicated in cardiac remodeling. We hypothesized that L-arginine (L-Arg) precursor of NO-synthase (NOS) and asymmetric dimethylarginine (ADMA), an inhibitor of NOS, are present in PF of cardiac patients and their altered levels may contribute to altered cardiac morphology.Methods
L-Arg and ADMA concentrations in plasma and PF, and echocardiographic parameters of patients undergoing coronary artery bypass graft (CABG, n = 28) or valve replacement (VR, n = 25) were determined.Results
We have found LV hypertrophy in 35.7% of CABG, and 80% of VR patients. In all groups, plasma and PF L-Arg levels were higher than that of ADMA. Plasma L-Arg level was higher in CABG than VR (75.7±4.6 μmol/L vs. 58.1±4.9 μmol/L, p = 0.011), whereas PF ADMA level was higher in VR than CABG (0.9±0.0 μmol/L vs. 0.7±0.0 μmol/L, p = 0.009). L-Arg/ADMA ratio was lower in the VR than CABG (VRplasma: 76.1±6.6 vs. CABGplasma: 125.4±10.7, p = 0.004; VRPF: 81.7±4.8 vs. CABGPF: 110.4±7.2, p = 0.009). There was a positive correlation between plasma L-Arg and ADMA in CABG (r = 0.539, p = 0.015); and plasma and PF L-Arg in CABG (r = 0.357, p = 0.031); and plasma and PF ADMA in VR (r = 0.529, p = 0.003); and PF L-Arg and ADMA in both CABG and VR (CABG: r = 0.468, p = 0.006; VR: r = 0.371, p = 0.034). The following echocardiographic parameters were higher in VR compared to CABG: interventricular septum (14.7±0.5 mm vs. 11.9±0.4 mm, p = 0.000); posterior wall thickness (12.6±0.3 mm vs. 11.5±0.2 mm, p = 0.000); left ventricular (LV) mass (318.6±23.5 g vs. 234.6±12.3 g, p = 0.007); right ventricular (RV) (33.9±0.9 cm2 vs. 29.7±0.7 cm2, p = 0.004); right atrial (18.6±1.0 cm2 vs. 15.4±0.6 cm2, p = 0.020); left atrial (19.8±1.0 cm2 vs. 16.9±0.6 cm2, p = 0.033) areas. There was a positive correlation between plasma ADMA and RV area (r = 0.453, p = 0.011); PF ADMA and end-diastolic (r = 0.434, p = 0.015) and systolic diameter of LV (r = 0.487, p = 0.007); and negative correlation between PF ADMA and LV ejection fraction (r = -0.445, p = 0.013) in VR.Conclusion
We suggest that elevated levels of ADMA in the PF of patients indicate upregulated RAS and reduced bioavailability of NO, which can contribute to the development of cardiac hypertrophy and remodeling. 相似文献2.
Context
Hyperphagia, low resting energy expenditure, and abnormal body composition contribute to severe obesity in Prader Willi syndrome (PWS). Irisin, a circulating myokine, stimulates “browning” of white adipose tissue resulting in increased energy expenditure and improved insulin sensitivity. Irisin has not been previously studied in PWS.Objectives
Compare plasma and salivary irisin in PWS adults and normal controls. Examine the relationship of irisin to insulin sensitivity and plasma lipids.Design and Study Participants
A fasting blood sample for glucose, lipids, insulin, leptin, adinopectin, and irisin was obtained from 22 PWS adults and 54 healthy BMI-matched volunteers. Saliva was collected for irisin assay in PWS and controls.Results
Fasting glucose (77±9 vs 83±7mg/dl, p = 0.004), insulin (4.1±2.0 vs 7.9±4.7μU/ml, p<0.001), and triglycerides (74±34 vs 109±71mg/dl, p = 0.007) were lower in PWS than in controls. Insulin resistance (HOMA-IR) was lower (0.79±0.041 vs 1.63±1.02, p<0.001) and insulin sensitivity (QUICKI) was higher (0.41±0.04 vs 0.36±0.03, p<0.001) in PWS. Plasma irisin was similar in both groups, but salivary irisin (64.5±52.0 vs 33.0±12.1ng/ml), plasma leptin (33.5±24.2 vs 19.7±19.3ng/ml) and plasma adinopectin (13.0±10.8 vs 7.6±4.5μg/ml) were significantly greater in PWS (p<0.001). In PWS, plasma irisin showed positive Pearson correlations with total cholesterol (r = 0.58, p = 0.005), LDL-cholesterol (r = 0.59, p = 0.004), and leptin (r = 0.43, p = 0.045). Salivary irisin correlated negatively with HDL-cholesterol (r = -0.50, p = 0.043) and positively with LDL-cholesterol (r = 0.51, p = 0.037) and triglycerides (r = 0.50, p = 0.041).Conclusions
Salivary irisin was markedly elevated in PWS although plasma irisin was similar to levels in controls. Significant associations with plasma lipids suggest that irisin may contribute to the metabolic phenotype of PWS. 相似文献3.
Michele Hepponstall Vera Ignjatovic Steve Binos Chantal Attard Vasiliki Karlaftis Yves d’Udekem Paul Monagle Igor E. Konstantinov 《PloS one》2015,10(3)
Background
Remote ischemic preconditioning (RIPC) has been applied in paediatric cardiac surgery. We have demonstrated that RIPC induces a proteomic response in plasma of healthy volunteers. We tested the hypothesis that RIPC modifies the proteomic response in children undergoing Tetralogy of Fallot (TOF) repair.Methods and Results
Children (n=40) were randomized to RIPC and control groups. Blood was sampled at baseline, after cardiopulmonary bypass (CPB) and 6, 12 and 24h post-CPB. Plasma was analysed by liquid chromatography mass spectrometry (LC-MS) in an untargeted approach. Peptides demonstrating differential expression (p<0.01) were subjected to tandem LC-MS/MS and protein identification. Corresponding proteins were identified using the NCBI protein database. There was no difference in age (7.3±3.5vs6.8±3.6 months)(p=0.89), weight (7.7±1.8vs7.5±1.9 kg)(p=0.71), CPB time (104±7vs94±7 min)(p=0.98) or aortic cross-clamp time (83±22vs75±20 min)(p=0.36). No peptides were differentially expressed at baseline or immediately after CPB. There were 48 peptides with higher expression in the RIPC group 6h post-CPB. This was no longer evident at 12 or 24h, with one peptide down-regulated in the RIPC group. The proteins identified were: inter-alpha globulin inhibitor (42.0±11.8 vs 820.8±181.1, p=0.006), fibrinogen preproprotein (59.3±11.2 vs 1192.6±278.3, p=0.007), complement-C3 precursor (391.2±160.9 vs 5385.1±689.4, p=0.0005), complement C4B (151.5±17.8 vs 4587.8±799.2, p=0.003), apolipoprotein B100 (53.4±8.3 vs 1364.5±278.2, p=0.005) and urinary proteinase inhibitor (358.6±74.9 vs 5758.1±1343.1, p=0.009). These proteins are involved in metabolism, haemostasis, immunity and inflammation.Conclusions
We provided the first comprehensive analysis of RIPC-induced proteomic changes in children undergoing surgery. The proteomic changes peak 6h post-CPB and return to baseline within 24h of surgery.Trial Registration
ACTR.org.au ACTRN12610000496011 相似文献4.
Mohamed Abd El Rahman Denise Haase Axel Rentzsch Julia Olchvary Hans-Joachim Sch?fers Wolfram Henn Stefan Wagenpfeil Hashim Abdul-Khaliq 《PloS one》2015,10(4)
Background
In asymptomatic Marfan syndrome (MFS) patients we evaluated the relationship between the types of fibrillin-1 (FBN1) gene mutation and possible altered left ventricular (LV) function as assessed by three-dimensional speckle tracking echocardiography (3D-STE).Methods and Results
Forty-five MFS patients (mean age 24±15 years) and 40 age-matched healthy controls were studied. Genetic evaluation for the FBN1 gene was carried on 32 MFS patients. Gene mutation (n = 15, 47%) was classified as mild when the mutation resulted in nearly normally functioning protein, while mutations resulting in abnormally function protein were considered to be severe (n = 17, 53%). All patients and controls underwent 3D-STE for evaluation of LV function by an echocardiographer blinded to the results of the genetic testing. Compared to controls, MFS patients had significantly lower 3D-STE derived LV ejection fraction (EF, 57.43±7.51 vs. 62.69±4.76%, p = 0.0001), global LV longitudinal strain (LS, 14.85±2.89 vs. 17.90±2.01%, p = 0.0001), global LV circumferential strain (CS, 13.93±2.81 vs. 16.82±2.17%, p = 0.0001) and global LV area strain (AS, 25.76±4.43 vs. 30.51±2.61%, p = 0.0001). Apart from the global LV LS all these parameters were significantly lower in patients with severe gene mutation than in those with mild mutation (p<0.05). In the multivariate linear regression analysis only the type of mutation had a significant influence on the 3D-STE derived LVEF (p = 0.017), global CS (p = 0.005) and global AS (p = 0.03).Conclusions
In asymptomatic MFS patients latent LV dysfunction can be detected using 3D STE. The LV dysfunction is mainly related to the severity of gene mutation, suggesting possible primary cardiomyopathy in MFS patients. 相似文献5.
Philipp M. Kazmierczak Egon Burian Ralf Eschbach Heidrun Hirner-Eppeneder Matthias Moser Lukas Havla Michel Eisenbl?tter Maximilian F. Reiser Konstantin Nikolaou Clemens C. Cyran 《PloS one》2015,10(9)
Objective
To investigate annexin-based optical fluorescence imaging (OI) for monitoring regorafenib-induced early cell death in experimental colon carcinomas in rats, validated by perfusion MRI and multiparametric immunohistochemistry.Materials and Methods
Subcutaneous human colon carcinomas (HT-29) in athymic rats (n = 16) were imaged before and after a one-week therapy with regorafenib (n = 8) or placebo (n = 8) using annexin-based OI and perfusion MRI at 3 Tesla. Optical signal-to-noise ratio (SNR) and MRI tumor perfusion parameters (plasma flow PF, mL/100mL/min; plasma volume PV, %) were assessed. On day 7, tumors underwent immunohistochemical analysis for tumor cell apoptosis (TUNEL), proliferation (Ki-67), and microvascular density (CD31).Results
Apoptosis-targeted OI demonstrated a tumor-specific probe accumulation with a significant increase of tumor SNR under therapy (mean Δ +7.78±2.95, control: -0.80±2.48, p = 0.021). MRI detected a significant reduction of tumor perfusion in the therapy group (mean ΔPF -8.17±2.32 mL/100 mL/min, control -0.11±3.36 mL/100 mL/min, p = 0.036). Immunohistochemistry showed significantly more apoptosis (TUNEL; 11392±1486 vs. 2921±334, p = 0.001), significantly less proliferation (Ki-67; 1754±184 vs. 2883±323, p = 0.012), and significantly lower microvascular density (CD31; 107±10 vs. 182±22, p = 0.006) in the therapy group.Conclusions
Annexin-based OI allowed for the non-invasive monitoring of regorafenib-induced early cell death in experimental colon carcinomas, validated by perfusion MRI and multiparametric immunohistochemistry. 相似文献6.
Dong Xu Xin You Zhengang Wang Qingyu Zeng Jianhua Xu Lindi Jiang Lu Gong Fengqi Wu Jieruo Gu Yi Tao Jinwei Chen Jiuliang Zhao Mengtao Li Yan Zhao Xiaofeng Zeng CSTAR co-authors 《PloS one》2015,10(8)
Objectives
Our study aimed to investigate the effect of cigarette smoking on the clinical phenotype of patients registered in the Chinese Systemic Lupus Erythematosus (SLE) Treatment and Research (CSTAR) group registry database, the first online registry of Chinese patients with SLE.Methods
A prospective cross-sectional study of Chinese SLE patients was conducted using the CSTAR. Our case-control analysis was performed on age- and gender-matched subjects to explore the potential effect of cigarette smoking on the clinical manifestation of SLE.Results
Smokers comprised 8.9% (65/730) of patients, and the ratio of females/males was 19/46. Thirty-nine patients were current smokers, and 26 were ex-smokers. Data showed significant differences between smokers and nonsmokers in the following areas: nephropathy (58.5% vs. 39.2%; p = 0.003), microscopic hematuria (30.8% vs. 19.1%; p = 0.025), proteinuria (53.8% vs. 34.4%; p = 0.002), and SLE Disease Activity Index(DAI) scores (12.38±8.95 vs. 9.83±6.81; p = 0.028). After adjusting for age and gender, significant differences between smokers and nonsmokers were found with photosensitivity (35.9% vs. 18%; p = 0.006), nephropathy (59.4% vs. 39.8%; p = 0.011), and proteinuria (54.7% vs. 35.2%). Although smokers tended to have greater disease severity compared with nonsmokers (SLEDAI scores: 12.58±8.89 vs.10.5±7.09), the difference was not significant (p = 0.081).Conclusions
Cigarette smoking triggers the development and exacerbation of SLE, especially with respect to renal involvement. Chinese smokers with SLE should be advised to discontinue cigarette use. 相似文献7.
Purpose
This study aimed to calculate the flexion-extension axis (FEA) of the knee through in-vivo knee kinematics data, and then compare it with two major anatomical axes of the femoral condyles: the transepicondylar axis (TEA) defined by connecting the medial sulcus and lateral prominence, and the cylinder axis (CA) defined by connecting the centers of posterior condyles.Methods
The knee kinematics data of 20 healthy subjects were acquired under weight-bearing condition using bi-planar x-ray imaging and 3D-2D registration techniques. By tracking the vertical coordinate change of all points on the surface of femur during knee flexion, the FEA was determined as the line connecting the points with the least vertical shift in the medial and lateral condyles respectively. Angular deviation and distance among the TEA, CA and FEA were measured.Results
The TEA-FEA angular deviation was significantly larger than that of the CA-FEA in 3D and transverse plane (3.45° vs. 1.98°, p < 0.001; 2.72° vs. 1.19°, p = 0.002), but not in the coronal plane (1.61° vs. 0.83°, p = 0.076). The TEA-FEA distance was significantly greater than that of the CA-FEA in the medial side (6.7 mm vs. 1.9 mm, p < 0.001), but not in the lateral side (3.2 mm vs. 2.0 mm, p = 0.16).Conclusion
The CA is closer to the FEA compared with the TEA; it can better serve as an anatomical surrogate for the functional knee axis. 相似文献8.
Objective
To compare the NK-1 receptor antagonist maropitant to morphine during and after surgery in dogs undergoing ovariohysterectomy (OHE).Methods
30 healthy female dogs were randomly divided to receive either a pre-anaesthetic dose of morphine (0.5 mg/kg SQ) or maropitant (1 mg/kg, SQ) prior to OHE. Anaesthesia was induced with propofol and maintained with isoflurane. Expired isoflurane concentration, heart rate (HR), systolic arterial pressure (SAP) and respiratory rate were measured. Post-operative pain scores and appetite were evaluated during the recovery period. Rescue analgesia (morphine 0.1 mg/kg IV) was administered as needed post-operatively based on blinded pain score assessments.Results
Although clinically comparable; during surgical stimulation, the maropitant group had lower HR (108±18 vs 115±24 bpm; p = 0.04), lower SAP (114±23 vs 125±23 mmHg; p = 0.003) and required slightly lower percent of isoflurane anaesthetic (1.35±0.2 vs 1.51±0.4%; p = 0.005), when compared to the morphine group. In the recovery period, the maropitant group had lower pain scores at extubation (1.7±0.7 vs 3.4±2.3; p = 0.0001) and were more likely to eat within 3 hours after extubation (64.7 vs 15.3%). However, post-operative rescue analgesia requirements were similar between groups. All other measured parameters were similar between groups. The overall difference observed between groups was small and all monitored and measured parameters were within the expected range for anesthetized dogs.Clinical Significance
No major differences in cardiorespiratory parameters or anaesthetic requirements were observed between maropitant and morphine when used as a pre-anesthetic agent for OHE. Further studies are necessary to fully elucidate the benefits of maropitant as a pre-anaesthetic agent for canine OHE. 相似文献9.
Background
Current guidelines recommend that caffeinated products should be avoided for at least 12 hours prior to regadenoson administration. We intended to examine the effect of caffeine consumption and of timing of last dose on hemodynamic effects after regadenoson administration for cardiac stress testing.Methods
332 subjects undergoing regadenoson stress testing were enrolled. Baseline characteristics, habits of coffee/caffeine exposure, baseline vital signs and change in heart rate, blood pressure, percent of maximal predicted heart rate, and percent change in heart rate were prospectively collected.Results
Non-coffee drinkers (group 1) (73 subjects) and subjects who last drank coffee >24 hours (group 3) (139 subjects) prior to regadenoson did not demonstrate any difference in systolic blood pressure, heart rate change, maximal predicted heart rate and percent change in heart rate. Systolic blood pressure change (15.2±17.1 vs. 7.2±10.2 mmHg, p = 0.001), heart rate change (32.2±14 vs. 27.3±9.6 bpm, p = 0.038) and maximal predicted heart rate (65.5±15.6 vs. 60.7±8.6%, p = 0.038) were significantly higher in non-coffee drinkers (group 1) compared to those who drank coffee 12–24 hours prior (group 2) (108 subjects). Subjects who drank coffee >24 hours prior (group 3) exhibited higher systolic blood pressure change (13±15.8 vs. 7±10.2, p = 0.007), and heart rate change (32.1±15.3 vs. 27.3±9.6, p = 0.017) as compared to those who drank coffee 12–24 hours prior to testing (group 2).Conclusions
Caffeine exposure 12–24 hours prior to regadenoson administration attenuates the vasoactive effects of regadenoson, as evidenced by a blunted rise in heart rate and systolic blood pressure. These results suggest that caffeine exposure within 24 hours may reduce the effects of regadenoson administered for vasodilatory cardiac stress testing. 相似文献10.
Cheuk-Chun Szeto Bonnie C. H. Kwan Kai-Ming Chow Phyllis M. S. Cheng Vickie W. K. Kwong Agnes S. M. Choy Man-Ching Law Chi-Bon Leung Philip K. T. Li 《PloS one》2015,10(10)
Background
Previous studies report conflicting results on the benefit of peritoneal dialysis (PD) patients treated with low glucose degradation product (GDP) solution. The effects of low GDP solution on body fluid status and arterial pulse wave velocity (PWV) have not been studied.Methods
We randomly assigned 68 incident PD patients to low GDP (Intervention Group) or conventional solutions (Control Group); 4 dropped off before they received the assigned treatment. Patients were followed for 52 weeks for changes in ultrafiltration, residual renal function, body fluid status and arterial PWV.Result
After 52 weeks, Intervention Group had higher overhydration (3.1 ± 2.6 vs 1.9 ± 2.2 L, p = 0.045) and extracellular water volume (17.7 ± 3.9 vs 15.8 ± 3.1 L, p = 0.034) than Control Group. There was no significant difference in PWV between groups. There was no significant difference in residual renal function between the Groups. Intervention Group had lower ultrafiltration volume than Control Group at 4 weeks (0.45 ± .0.61 vs 0.90 ± 0.79 L/day, p = 0.013), but the difference became insignificant at later time points. Intervention Group had lower serum CRP levels than Control Group (4.17 ± 0.77 vs 4.91 ± 0.95 mg/dL, p < 0.0001).Conclusion
Incident PD patients treated with low GDP solution have less severe systemic inflammation but trends of less ultrafiltration, and more fluid accumulation. However, the effects on ultrafiltration and fluid accumulation disappear with time. The long term effect of low GDP solution requires further study.Trial Registration
ClinicalTrials.gov NCT00966615 相似文献11.
Lóránt Dienes Huba J. Kiss Kristóf Perényi Zoltán Z. Nagy M. Carmen Acosta Juana Gallar Illés Kovács 《PloS one》2015,10(10)
Purpose
To investigate corneal sensitivity to selective mechanical, chemical, and thermal stimulation and to evaluate their relation to dry eye symptoms in patients with keratoconus.Methods
Corneal sensitivity to mechanical, chemical, and thermal thresholds were determined using a gas esthesiometer in 19 patients with keratoconus (KC group) and in 20 age-matched healthy subjects (control group). Tear film dynamics was assessed by Schirmer I test and by the non-invasive tear film breakup time (NI-BUT). All eyes were examined with a rotating Scheimpflug camera to assess keratoconus severity.Results
KC patients had significatly decreased tear secretion and significantly higher ocular surface disease index (OSDI) scores compared to controls (5.3±2.2 vs. 13.2±2.0 mm and 26.8±15.8 vs. 8.1±2.3; p<0.001). There was no significant difference in NI-BUT between the two groups (KC: 9.8±4.8 vs. control: 10.7±3.8; p>0.05). The mean threshold for selective mechanical (KC: 139.2±25.8 vs. control: 109.1±24.0 ml/min), chemical (KC: 39.4±3.9 vs. control: 35.2±1.9%CO2), heat (KC: 0.91±0.32 vs. control: 0.54±0.26 Δ°C) and cold (KC: 1.28±0.27 vs. control: 0.98±0.25 Δ°C) stimulation in the KC patients were significantly higher than in the control subjects (p<0.001, for all parameters). No correlation was found between age and mechanical, chemical, heat or cold thresholds in the patients with KC (p>0.05), whereas in the control subjects both mechanical (r = 0.52, p = 0.02), chemical (r = 0.47, p = 0.04), heat (r = 0.26, p = 0.04) and cold threshold (r = 0.40, p = 0.03) increased with age. In the KC group, neither corneal thickness nor tear flow, NI-BUT or OSDI correlated significantly with mechanical, chemical, heat or cold thresholds (p>0.05 for all variables).Conclusions
Corneal sensitivity to different types of stimuli is decreased in patients with keratoconus independently of age and disease severity. The reduction of the sensory input from corneal nerves may contribute to the onset of unpleasant sensations in these patients and might lead to the impaired tear film dynamics. 相似文献12.
Andreas Schaefer Yvonne Schneeberger Justus Stenzig Daniel Biermann Marisa Jelinek Hermann Reichenspurner Thomas Eschenhagen Heimo Ehmke Alexander P. Schwoerer 《PloS one》2016,11(2)
Objectives
Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC) and heterotopic heart transplantation (hHTx) in rats.Methods
To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations.Results
50 TAC procedures were performed with a survival of 92% (46/50). When compared to healthy rats left ventricular surface decreased to 5.8±1.0 mm² (vs. 9.6± 2.4 mm²) (p = 0.001) after three weeks with a fractional shortening (FS) of 23.7± 4.3% vs. 28.2± 1.5% (p = 0.01). Six weeks later, systolic function decreased to 17.1± 3.2% vs. 28.2± 1.5% (p = 0.0001) and left ventricular inner surface increased to 19.9±1.1 mm² (p = 0.0001). Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46). All transplanted organs survived two weeks of mechanical unloading.Discussion
Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure. 相似文献13.
Bernhard Scheiner Mattias Mandorfer Philipp Schwabl Berit Anna Payer Theresa Bucsics Simona Bota Maximilian C. Aichelburg Katharina Grabmeier-Pfistershammer Albert St?ttermayer Peter Ferenci Michael Trauner Markus Peck-Radosavljevic Thomas Reiberger 《PloS one》2015,10(11)
Background
Faster fibrosis progression and hepatic steatosis are hallmarks of HIV/HCV coinfection. A single nucleotide polymorphism (SNP) of the PNPLA3-gene is associated with development of non-alcoholic steatohepatitis and a worse outcome in alcoholic liver disease. However, the role of PNPLA3 rs738409 SNP on liver fibrosis and steatosis, portal hypertension, and virological response in HIV/HCV coinfection remains unclear.Methods
In this cross-sectional study PNPLA3 (rs738409) and IL28B (rs12979860) SNPs were determined in 177 HIV/HCV coinfected patients. Liver fibrosis and steatosis—staged by liver biopsy and transient elastography using the Controlled Attenuation Parameter (CAP)–and portal hypertension (hepatic venous pressure gradient, HVPG) were compared across PNPLA3 genotypes.Results
75 (42.4%) patients tested positive for a PNPLA3 minor/major risk allele (G/C:66; G/G:9) showed comparable fibrosis stages (median F2 vs. F2; p = 0.292) and similar amounts of hepatic steatosis (CAP: 203.5±41.9 vs. 215.5±59.7dB/m; p = 0.563) as compared to patients without a PNPLA3 risk allele. Advanced liver fibrosis was neither associated with PNPLA3 (p = 0.253) nor IL28B-genotype (p = 0.628), but with HCV-GT3 (p = 0.003), higher BMI (p = 0.008) and higher age (p = 0.007). Fibrosis progression rate (0.27±0.41 vs. 0.20±0.26 units/year; p = 0.984) and HVPG (3.9±2.6 vs. 4.4±3.0 mmHg; p = 0.472) were similar in patients with and without PNPLA3 risk alleles. SVR rates to PEGIFN/RBV therapy were similar across PNPLA3 genotypes.Conclusions
The presence of a PNPLA3 risk allele had no independent impact on liver disease or virological response rates to PEGIFN/RBV therapy in our cohort of HIV/HCV coinfected patients. 相似文献14.
Gaetane Nocturne Stephan Pavy Saida Boudaoud Raphaèle Seror Philippe Goupille Philippe Chanson Désirée van der Heijde Floris van Gaalen Francis Berenbaum Xavier Mariette Karine Briot Antoine Feydy Pascal Claudepierre Philippe Dieudé Joanne Nithitham Kimberly E. Taylor Lindsey A. Criswell Maxime Dougados Christian Roux Corinne Miceli-Richard 《PloS one》2015,10(8)
Objectives
To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors.Methods
The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and <3 years) suggestive of AxSpA. DKK-1 and SOST serum levels were assessed at baseline and were compared between the subgroup of patients fulfilling ASAS criteria for SpA (n = 486; 68.6%) and 80 healthy controls.Results
Mean SOST serum levels were lower in ASAS+ patients than healthy controls (49.21 ± 25.9 vs. 87.8 ± 26 pmol/L; p<0.0001). In multivariate analysis, age (p = 5.4 10−9), CRP level (p<0.0001) and serum DKK-1 level (p = 0.001) were associated with SOST level. Mean DKK-1 serum levels were higher in axial SpA patients than controls (30.03 ± 15.5 vs. 11.6 ± 4.2 pmol/L; p<0.0001). In multivariate analysis, DKK-1 serum levels were associated with male gender (p = 0.03), CRP level (p = 0.006), SOST serum level (p = 0.002) and presence of sacroiliitis on radiography (p = 0.05). Genetic association testing of 10 SNPs encompassing the DKK-1 locus failed to demonstrate a significant contribution of genetics to control of DKK-1 serum levels.Conclusions
DKK-1 serum levels were increased and SOST levels were decreased among a large cohort of patients with early axial SpA compared to healthy controls. DKK-1 serum levels were mostly associated with biological inflammation and SOST serum levels. 相似文献15.
Dominic Ehrmann Nikola Bergis-Jurgan Thomas Haak Bernhard Kulzer Norbert Hermanns 《PloS one》2016,11(1)
Background
The effectiveness of an intervention in clinical practice is often reduced compared to the efficacy demonstrated in a randomised controlled trial (RCT). In this comparative effectiveness study, the RCT-proven efficacy of a diabetes education programme for type 1 diabetic patients (PRIMAS) was compared to the effectiveness observed in an implementation trial (IT) under routine care conditions.Methods
75 patients with type 1 diabetes received PRIMAS through an RCT, whereas 179 patients were observed in an implementation trial. Baseline characteristics and treatment outcomes at the 6-month follow-up (improvement of HbA1c, hypoglycaemia problems, and diabetes-related distress) were compared.Results
At baseline, the type 1 diabetic patients in the RCT had a significant longer diabetes duration (18.7±12.3 vs. 13.8±12.7 yrs., p = .005), lower self-efficacy scores (21.9±4.7 vs. 23.7±6.1, p = .02) and a greater number of diabetes complications (0.8±1.3 vs. 0.4±0.9, p = .02). After 6 months, PRIMAS achieved comparable effects under RCT and implementation trial conditions, as demonstrated by improvement in HbA1c (-0.36%±1.1 vs. -0.37±1.2; Δ -0.01, 95% CI -0.33 to 0.31) and hypoglycaemia unawareness (-0.5±1.4 vs. -0.3±1.4; Δ 0.18, 95% CI -0.21 to 0.57). The likelihood of clinical improvement did not depend on the trial setting (RCT vs. IT: OR 1.18, 95% CI 0.60 to 2.33). The participants with worse glycaemic control (OR 1.40, 95% CI 1.02 to 1.92), hypoglycaemia problems (OR 2.13, 95% CI 1.53 to 2.97) or elevated diabetes distress (OR 1.40, 95% CI 1.03 to 1.89) had a better chance of clinical improvement.Conclusions
The effectiveness of PRIMAS under routine care conditions was comparable to the efficacy demonstrated in the RCT. Clinical improvement was independent of the setting in which PRIMAS was evaluated. The PRIMAS education programme for type 1 diabetes can be delivered under conditions of routine care without a loss of effectiveness, compared to its original evaluation in an RCT. 相似文献16.
Jiwon Kim Chaitanya B. Medicherla Claudia L. Ma Attila Feher Nina Kukar Alexi Geevarghese Parag Goyal Evelyn Horn Richard B. Devereux Jonathan W. Weinsaft 《PloS one》2016,11(1)
Background
Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress.Methods and Results
The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5±3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34±10 vs. 39±9%; p = 0.01) but similar LVEF (40±21 vs. 39±18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17±7 vs. 12±6 kPa; p<0.001) corresponding to increased RV end-systolic volume (143±79 vs. 110±36 ml; p = 0.006), myocardial mass (60±21 vs. 53±17 gm; p = 0.04), and PASP (52±18 vs. 41±18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04–1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14–1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69–1.20]; p = 0.5) [model χ2 = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001).Conclusion
Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling. 相似文献17.
Maximilian J. Hartel Andreas Petersik Anne Schmidt Daniel Kendoff Jakob Nüchtern Johannes M. Rueger Wolfgang Lehmann Lars G. Grossterlinden 《PloS one》2016,11(3)
Introduction
Exact knowledge of femoral neck inclination and torsion angles is important in recognizing, understanding and treating pathologic conditions in the hip joint. However, published results vary widely between different studies, which indicates that there are persistent difficulties in carrying out exact measurements.Methods
A three dimensional modeling and analytical technology was used for the analysis of 1070 CT datasets of skeletally mature femurs. Individual femoral neck angles and torsion angles were precisely computed, in order to establish whether gender, age, body mass index and ethnicity influence femoral neck angles and torsion angles.Results
The median femoral neck angle was 122.2° (range 100.1–146.2°, IQR 117.9–125.6°). There are significant gender (female 123.0° vs. male 121.5°; p = 0.007) and ethnic (Asian 123.2° vs. Caucasian 121.9°; p = 0.0009) differences. The median femoral torsion angle was 14.2° (-23.6–48.7°, IQR 7.4–20.4°). There are significant gender differences (female 16.4° vs. male 12.1°; p = 0.0001). Femoral retroversion was found in 7.8% of the subjects.Conclusion
Precise femoral neck and torsion angles were obtained in over one thousand cases. Systematic deviations in measurement due to human error were eliminated by using automated high accuracy morphometric analysis. Small but significant gender and ethnic differences were found in femoral neck and torsion angles. 相似文献18.
Katrina J. Curtis Katie A. O’Brien Rebecca J. Tanner Juliet I. Polkey Magdalena Minnion Martin Feelisch Michael I. Polkey Lindsay M. Edwards Nicholas S. Hopkinson 《PloS one》2015,10(12)
Background
Dietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD.Methods
We performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9mmoles nitrate) or placebo (nitrate-depleted beetroot juice) 3 hours prior to endurance cycle ergometry, performed at 70% of maximal workload assessed by a prior incremental exercise test. After a minimum washout period of 7 days the protocol was repeated with the crossover beverage.Results
21 subjects successfully completed the study (age 68±7years; BMI 25.2±5.5kg/m2; FEV1 percentage predicted 50.1±21.6%; peak VO2 18.0±5.9ml/min/kg). Resting diastolic blood pressure fell significantly with nitrate supplementation compared to placebo (-7±8mmHg nitrate vs. -1±8mmHg placebo; p = 0.008). Median endurance time did not differ significantly; nitrate 5.65 (3.90–10.40) minutes vs. placebo 6.40 (4.01–9.67) minutes (p = 0.50). However, isotime oxygen consumption (VO2) was lower following nitrate supplementation (16.6±6.0ml/min/kg nitrate vs. 17.2±6.0ml/min/kg placebo; p = 0.043), and consequently nitrate supplementation caused a significant lowering of the amplitude of the VO2-percentage isotime curve.Conclusions
Acute administration of oral nitrate did not enhance endurance exercise performance; however the observation that beetroot juice caused reduced oxygen consumption at isotime suggests that further investigation of this treatment approach is warranted, perhaps targeting a more hypoxic phenotype.Trial Registration
ISRCTN Registry ISRCTN66099139 相似文献19.
Paul H. Falcone Chih Yin Tai Laura R. Carson Jordan M. Joy Matt M. Mosman Roxanne M. Vogel Tyler R. McCann Kevin P. Crona J. Daniel Griffin Michael P. Kim Jordan R. Moon 《PloS one》2015,10(4)
Background
Weight loss benefits of multi-ingredient supplements in conjunction with a low-calorie, high-protein diet in young women are unknown. Therefore, the purpose of this study was to investigate the effects of a three-week low-calorie diet with and without supplementation on body composition.Methods
Thirty-seven recreationally-trained women (n = 37; age = 27.1 ± 4.2; height = 165.1 ± 6.4; weight = 68.5 ± 10.1; BMI = 25.1 ± 3.4) completed one of the following three-week interventions: no change in diet (CON); a high-protein, low-calorie diet supplemented with a thermogenic, conjugated linoleic acid (CLA), a protein gel, and a multi-vitamin (SUP); or the high-protein diet with isocaloric placebo supplements (PLA). Before and after the three-week intervention, body weight, %Fat via dual X-ray absorptiometry (DXA), segmental fat mass via DXA, %Fat via skinfolds, and skinfold thicknesses at seven sites were measured.Results
SUP and PLA significantly decreased body weight (SUP: PRE, 70.47 ± 8.01 kg to POST, 67.51 ± 8.10 kg; PLA: PRE, 67.88 ± 12.28 kg vs. POST, 66.38 ± 11.94 kg; p ≤ 0.05) with a greater (p ≤ 0.05) decrease in SUP than PLA or CON. SUP and PLA significantly decreased %Fat according to DXA (SUP: PRE, 34.98 ± 7.05% to POST, 32.99 ± 6.89%; PLA: PRE, 34.22 ± 6.36% vs. POST, 32.69 ± 5.84%; p ≤ 0.05), whereas only SUP significantly decreased %Fat according to skinfolds (SUP: PRE, 27.40 ± 4.09% to POST, 24.08 ± 4.31%; p ≤ 0.05). SUP significantly (p ≤ 0.05) decreased thicknesses at five skinfolds (chest, waist, hip, subscapular, and tricep) compared to PLA, but not at two skinfolds (axilla and thigh).Conclusions
The addition of a thermogenic, CLA, protein, and a multi-vitamin to a three-week low-calorie diet improved weight loss, total fat loss and subcutaneous fat loss, compared to diet alone. 相似文献20.
Carsten J. Beller Mina Farag Sepali Wannaku Philipp Seppelt Rawa Arif Arjang Ruhparwar Matthias Karck Alexander Weymann Klaus Kallenbach 《PloS one》2015,10(4)