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1.
Saloua El Messaoudi Tim H. Schreuder Roel D. Kengen Gerard A. Rongen Petra H. van den Broek Dick H. J. Thijssen Niels P. Riksen 《PloS one》2014,9(4)
Introduction
Large prospective studies in patients with type 2 diabetes mellitus have demonstrated that metformin treatment improves cardiovascular prognosis, independent of glycemic control. Administration of metformin potently limits infarct size in murine models of myocardial infarction. This study examined, for the first time in humans, whether metformin limits ischemia-reperfusion (IR) injury in vivo using a well-validated forearm model of endothelial IR-injury.Methods
Twenty-eight healthy volunteers (age 41±6 years, 10 male/16 female) were randomized between pretreatment with metformin (500 mg three times a day for 3 days) or no treatment in a Prospective Randomized Open Blinded Endpoint study. Brachial artery flow mediated dilation (FMD) was measured before and after 20 minutes of forearm ischemia and 20 minutes of reperfusion. FMD analysis was performed offline by investigators blinded for the treatment arm.Results
Baseline FMD did not differ between metformin pretreatment and no pretreatment (6.9±3.6% and 6.1±3.5%, respectively, p = 0.27, n = 26). FMD was significantly lower after forearm IR in both treatment arms (4.4±3.3% and 4.3±2.8%, respectively, P<0.001 in both conditions). A linear mixed model analysis revealed that metformin treatment did not prevent the decrease in FMD by IR.Conclusion
A 3 day treatment with metformin in healthy, middle-aged subjects does not protect against endothelial IR-injury, measured with brachial artery FMD after forearm ischemia. Further studies are needed to clarify what mechanism underlies the cardiovascular benefit of metformin treatment.Trial Registration
ClinicalTrials.gov NCT01610401 相似文献2.
Peng-Yuan Zhuang Jun Shen Xiao-Dong Zhu Ju-Bo Zhang Zhao-You Tang Lun-Xiu Qin Hui-Chuan Sun 《PloS one》2013,8(3)
Background
Interferon (IFN)-α is effective in inhibiting tumor growth and metastasis of hepatocellular carcinoma (HCC). However, the biologic mechanisms of IFN-α treatment in lung metastasis are not yet clear.Methods
The effect of IFN-α treatment was studied by using an orthotopic xenograft model and measuring tumor size and lung metastasis. Pretreatment with IFN-α before implantation of tumor was done to explore the effect of IFN-α on lung tissues. Cytokines and macrophages were measured by immunohistochemistry and/or PCR assay, using human origin or mouse origin primers to differentiate the sources. Circulating tumor cells (CTCs) were also assayed by flow cytometry.Results
IFN-α treatment did not decrease the number of CTCs (0.075%±0.020% versus 0.063%±0.018%, P = 0.574, IFN-α–treated versus control groups), but did decrease the number and size of lung metastasis (number: 1.75±1.0 versus 28.0±6.3, P = 0.008; size [pixels]: 116.8±72.2 versus 5226.4±1355.7, P = 0.020), and inhibited macrophage infiltration (0.20%±0.04% versus 1.36%±0.21%, P = 0.0058) and alteration of matrix metalloproteinase (MMP)-9 expression (mean integrated optical density (IOD): 5.1±1.7 versus 21.9±0.4, P<0.000) in the lung, which was independent of the primary tumor.Conclusion
IFN-α inhibited lung metastasis by directly modulating the lung microenvironment. 相似文献3.
Rachel Hallmark James T. Patrie Zhenqi Liu Glenn A. Gaesser Eugene J. Barrett Arthur Weltman 《PloS one》2014,9(1)
Purpose
To examine the effects of exercise intensity on acute changes in endothelial function in lean and obese adults.Methods
Sixteen lean (BMI <25, age 23±3 yr) and 10 obese (BMI >30, age 26±6 yr) physically inactive adults were studied during 3 randomized admissions [control (C, no exercise), moderate-intensity exercise (M, @ lactate threshold (LT)) and high-intensity exercise (H, midway between LT and VO2peak) (30 min)]. Endothelial function was assessed by flow-mediated dilation (FMD) at baseline and 1, 2, and 4 h post-exercise.Results
RM ANCOVA revealed significant main effects for group, time, and group x condition interaction (p<0.05). A diurnal increase in FMD was observed in lean but not obese subjects. Lean subjects exhibited greater increases in FMD than obese subjects (p = 0.0005). In the obese group a trend was observed for increases in FMD at 2- and 4-hr after M (p = 0.08). For lean subjects, FMD was significantly elevated at all time points after H. The increase in FMD after H in lean subjects (3.2±0.5%) was greater than after both C (1.7±0.4%, p = 0.015) and M (1.4±0.4%, p = 0.002). FMD responses of lean and obese subjects significantly differed after C and H, but not after M.Conclusion
In lean young adults, high-intensity exercise acutely enhances endothelial function, while moderate-intensity exercise has no significant effect above that seen in the absence of exercise. The FMD response of obese adults is blunted compared to lean adults. Diurnal variation should be considered when examining the effects of acute exercise on FMD. 相似文献4.
Purpose
Obstructive sleep apnea (OSA) is a common disorder affecting 15–24% of the adults and is associated with increased risk of hypertension and atherosclerosis. The exact mechanisms underlying hypertension in OSA are not entirely clear. YKL-40/Chitinase-3-like protein-1 is a circulating moiety with roles in injury, repair and angiogenesis that is dysregulated in atherosclerosis and a number of other diseases. We sought to determine the role of YKL-40 in endothelial dysfunction and hypertension in OSA.Methods
We studies 23 normotensive OSA (N-OSA) and 14 hypertensive OSA (H-OSA) without diabetes and apparent cardiovascular disease. Endothelial-dependent nitric oxide-mediated vasodilatory capacity was assessed by flow-mediated vasodilation (FMD). YKL-40, vascular endothelial growth factor (VEGF) and the soluble form of VEGF receptor-1or sFlt-1 were measured in plasma using ELISA methodology.Results
N-OSA subjects aged 49.1±2.3 years and H-OSA aged 51.3±1.9 years with BMI 36.1±1.6 and 37.6±1.9 kg/m2, respectively. The apnea-hypopnea index (AHI) was 41±5 events/hr in N-OSA and 46±6 in H-OSA with comparable degree of oxygen desaturations during sleep. FMD was markedly impaired in H-OSA (8.3%±0.8) compared to N-OSA (13.2%±0.6, P<0.0001). Plasma YKL-40 was significantly elevated in H-OSA (55.2±7.9 ng/ml vs. 35.6±4.2 ng/ml in N-OSA, P = 0.02) and had an inverse relationship with FMD (r = −0.52, P = 0.013). There was a significant positive correlation between sFlt-1/VEGF, a measure of decreased VEGF availability, and YKL-40 (r = 0.42, P = 0.04).Conclusion
The levels of plasma YKL-40 were elevated in H-OSA group and inversely correlated with the endothelial-dependent vasodilatory capacity whereas there was a positive correlation between sFlt-1/VEGF and YKL-40. These findings suggest that YKL-40 is dysregulated, in part, due to perturbation of VEGF signaling, and may contribute to endothelial dysfunction and hypertension in OSA. 相似文献5.
Dimitrios Daoussis Athanassios C Tsamandas Stamatis-Nick C Liossis Ioannis Antonopoulos Elli Karatza Georgios Yiannopoulos Andrew P Andonopoulos 《Arthritis research & therapy》2012,14(3):R145
Introduction
Recently, several studies assessing the clinical efficacy of rituximab (RTX) in systemic sclerosis (SSc) have reported encouraging results. We aimed at exploring whether RTX exerts its beneficial effects on fibrosis through attenuation of platelet-derived growth factor receptor (PDGFR) pathway activation.Methods
We immunohistochemically assessed skin biopsies obtained from eight patients with SSc prior to and 6 months following RTX treatment, three control SSc patients (at the same time points) and three healthy subjects. We assessed the expression of platelet-derived growth factor, PDGFR and phosphorylated (activated) PDGFR.Results
We found a strong correlation of PDGFRα and PDGFRβ expression on spindle-like cells and collagen deposition in SSc biopsies (r = 0.97 and r = 0.96 for PDGFRα and PDGFRβ, respectively; P < 0.0001 for both), indicating a strong link between PDGFR expression and fibrosis. Expression of PDGFRα and PDGFRβ in the papillary dermis significantly decreased following RTX administration (mean ± standard error of the mean at baseline vs. 6 months, respectively: PDGFRα, 42.05 ± 5.03 vs. 26.85 ± 3.00, P = 0.004; and PDGFRβ, 37.14 ± 4.94 vs. 24.01 ± 3.27, P = 0.012). Similarly, expression of phosphorylated PDGFRα and PDGFRβ in the papillary dermis significantly decreased following RTX administration (P = 0.006 and P = 0.013 for phospho-PDGFRα and phospho-PDGFRβ, respectively). No changes in platelet-derived growth factor tissue expression or serum levels were found following RTX treatment.Conclusion
RTX may favorably affect skin fibrosis through attenuation of PDGFR expression and activation, a finding that supports a disease-modifying role of RTX in SSc. Large-scale, multicenter studies are needed to further explore the efficacy of RTX in SSc. 相似文献6.
Alessandra Vacca Roberta Montisci Pietro Garau Paolo Siotto Matteo Piga Alberto Cauli Massimo Ruscazio Luigi Meloni Sabino Iliceto Alessandro Mathieu 《Arthritis research & therapy》2013,15(1):R8
Introduction
Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome.Methods
Forty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7- ± 3.5-year follow-up.Results
Nineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r = -0.57, P <0.0001) was observed; in addition, CFR was significantly reduced (2.21 ± 0.38) in patients with WMA as compared to those without (2.94 ± 0.60) (P <0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7- ± 3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests.Conclusions
A-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases. 相似文献7.
Michael Osthoff Gene-Siew Ngian Melinda M Dean Mandana Nikpour Wendy Stevens Susanna Proudman Damon P Eisen Joanne Sahhar 《Arthritis research & therapy》2014,16(6)
Introduction
Repetitive episodes of ischemia and reperfusion (I/R) are a cardinal feature of the pathogenesis of systemic sclerosis (SSc), which precedes tissue fibrosis. The complement system is a key mediator of tissue damage after I/R, primarily by activation of the lectin pathway. This study investigated whether serum levels and polymorphisms of mannose-binding lectin (MBL) and ficolin-2 (FCN2), two pattern recognition receptors of the lectin pathway, are associated with the predisposition to and clinical features of SSc.Methods
A case-control study was undertaken involving 90 patients with SSc from a single SSc outpatient clinic and 90 age- and sex-matched blood donors. MBL and FCN2 levels and polymorphisms were measured in both groups, and in cases correlated with clinical data.Results
MBL levels and genotypes were equally distributed in cases and controls while there were some significant differences in FCN2 polymorphisms. Median MBL levels were higher in SSc cases with diffuse disease compared with controls (2.6 versus 1.0 μg/ml, P <0.001).In cases, higher MBL levels were associated with the presence of clinical findings associated with vascular dysfunction and local tissue damage (digital ulcers, calcinosis and pitting). Moreover, MBL levels were associated with fibrotic disease manifestations as evidenced by the presence of diffuse disease (median 2.6 versus 0.8 μg/ml, P = 0.002), the modified Rodnan skin score (r = 0.39, P <0.001), and interstitial lung disease as measured by forced vital capacity (r = −0.33, P = 0.001). Importantly, MBL levels also correlated with the Scleroderma Health Assessment Questionnaire scores (r = 0.33, P = 0.002). The results for FCN2 levels were less striking. Phenotypic MBL results were largely confirmed by analysis of MBL polymorphisms. MBL levels were not associated with the presence of autoantibodies or hypocomplementaemia.Conclusions
Overall, predisposition to SSc was not influenced by the lectin pathway of complement in our matched case-control study. However, our preliminary data suggest that MBL, and to a lesser extent FCN2, may modulate disease manifestations of SSc, particularly in diffuse cutaneous disease.Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0480-6) contains supplementary material, which is available to authorized users. 相似文献8.
Annica Nordin Kerstin Jensen-Urstad Lena Bj?rn?dal Susanne Pettersson Anders Larsson Elisabet Svenungsson 《Arthritis research & therapy》2013,15(4):R87
Introduction
While microvascular disease is well described in systemic sclerosis (SSc), it is still unclear whether the occurrence of ischemic macrovascular events and atherosclerosis is enhanced among patients with SSc.Methods
In this study, 111 SSc patients (74% of prevalent cases in Stockholm County) and 105 age- and sex-comparable population controls were investigated. Previous ischemic arterial events were tabulated. As surrogate measures of atherosclerosis, plaque occurrence and intima-media thickness (IMT) were determined with carotid ultrasound and the ankle-brachial index (ABI) was calculated. Traditional cardiovascular risk factors were recorded and we also measured biomarkers indicating systemic inflammation and endothelial activation/dysfunction.Results
Mean age was 62 ± 12 years for patients and controls. Ischemic arterial events were more common, due to increased occurrence of ischemic heart disease (IHD) and ischemic peripheral vascular disease (IPVD), in the patient group (12% vs. 4%, P = 0.03 and 9% vs. 0%, P = 0.003 respectively). On a group level, there was no difference regarding the occurrence of ischemic cerebrovascular disease, the frequency of plaques, IMT or ABI between SSc patients and controls. Subgroup analyses revealed that patients with anticentromere antibodies (ACA+) had more plaques and more ischemic arterial events compared to other SSc patients (67% vs. 39% and 32% vs. 11%; P = 0.006 and P = 0.01, respectively) and compared to controls (67% vs. 41% and 32% vs. 7%, P = 0.02 and P = 0.0003, respectively). Biomarkers of inflammation/endothelial activation were generally increased among SSc patients.Conclusions
Patients with SSc are at enhanced risk for IHD and IPVD. The ACA+ SSc subgroup was particularly affected with both ischemic arterial events and premature atherosclerosis. The microvascular vulnerability of ACA+ patients is previously well documented. We demonstrate that ACA+ SSc patients have an enhanced risk of macrovascular injury as well. This group should be followed closely and modifiable cardiovascular risk factors should be treated at an early stage. 相似文献9.
Mélanie Gilson Laure Gossec Xavier Mariette Dalenda Gherissi Marie-Hélène Guyot Jean-Marie Berthelot Daniel Wendling Christian Michelet Pierre Dellamonica Florence Tubach Maxime Dougados Dominique Salmon 《Arthritis research & therapy》2010,12(4):R145
Introduction
The objective of this study was to assess natural microbial agents, history and risk factors for total joint arthroplasty (TJA) infections in patients receiving tumor necrosis factor (TNF)α-blockers, through the French RATIO registry and a case-control study.Methods
Cases were TJA infections during TNFα-blocker treatments. Each case was compared to two controls (with TJA and TNFα-blocker therapy, but without TJA infection) matched on age (±15 years), TJA localization, type of rheumatic disorder and disease duration (±15 years). Statistical analyses included univariate and multivariate analyses with conditional logistic regression.Results
In the 20 cases (18 rheumatoid arthritis), TJA infection concerned principally the knee (n = 12, 60%) and the hip (n = 5, 25%). Staphylococcus was the more frequent microorganism involved (n = 15, 75%). Four patients (20%) were hospitalized in an intensive care unit and two died from infection. Eight cases (40%) versus 5 controls (13%) had undergone primary TJA or TJA revision for the joint subsequently infected during the last year (P = 0.03). Of these procedures, 5 cases versus 1 control were performed without withdrawing TNFα-blockers (P = 0.08). In multivariate analysis, predictors of infection were primary TJA or TJA revision for the joint subsequently infected within the last year (odds ratio, OR = 88.3; 95%CI 1.1-7,071.6; P = 0.04) and increased daily steroid intake (OR = 5.0 per 5 mg/d increase; 1.1-21.6; P = 0.03). Case-control comparisons showed similar distribution between TNFα-blockers (P = 0.70).Conclusions
In patients receiving TNFα-blockers, TJA infection is rare but potentially severe. Important risk factors are primary TJA or TJA revision within the last year, particularly when TNFα-blockers are not interrupted before surgery, and the daily steroid intake. 相似文献10.
Shogo Watanabe Eisuke Amiya Masafumi Watanabe Munenori Takata Atsuko Ozeki Aya Watanabe Shuichi Kawarasaki Tomoko Nakao Yumiko Hosoya Kohzo Nagata Ryozo Nagai Issei Komuro 《PloS one》2014,9(10)
Purpose
The physiological role of vasomotion, rhythmic oscillations in vascular tone or diameter, and its underlying mechanisms are unknown. We investigated the characteristics of brachial artery vasomotion in patients with ischemic heart disease (IHD).Methods
We performed a retrospective study of 37 patients with IHD. Endothelial function was assessed using flow-mediated dilation (FMD), and power spectral analysis of brachial artery diameter oscillations during FMD was performed. Frequency-domain components were calculated by integrating the power spectrums in three frequency bands (in ms2) using the MemCalc (GMS, Tokyo, Japan): very-low frequency (VLF), 0.003–0.04 Hz; low frequency (LF), 0.04–0.15 Hz; and high frequency (HF), 0.15–0.4 Hz. Total spectral power (TP) was calculated as the sum of all frequency bands, and each spectral component was normalized against TP.Results
Data revealed that HF/TP closely correlated with FMD (r = −0.33, p = 0.04), whereas VLF/TP and LF/TP did not. We also explored the relationship between elevated C-reactive protein (CRP) levels and vasomotion. HF/TP was significantly increased in subjects with high CRP levels (CRP;>0.08 mg/dL) compared with subjects with low CRP levels (0.052±0.026 versus 0.035±0.022, p<0.05). The HF/TP value closely correlated with CRP (r = 0.24, p = 0.04), whereas the value of FMD did not (r = 0.023, p = 0.84). In addition, elevated CRP levels significantly increased the value of HF/TP after adjustment for FMD and blood pressure (β = 0.33, p<0.05).Conclusion
The HF component of brachial artery diameter oscillation during FMD measurement correlated well with FMD and increased in the presence of elevated CRP levels in subjects with IHD. 相似文献11.
Background
Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are systemic autoimmune connective tissue diseases that share overlapping clinico-pathological features. It is highly probable that there is an overlap in epigenetic landscapes of both diseases. This study aimed to identify similarities in DNA methylation changes in genes involved in SLE and SSc. Global DNA methylation and twelve genes selected on the basis of their involvement in inflammation, autoimmunity and/or fibrosis were analyzed using PCR arrays in three groups, each of 30 Black South Africans with SLE and SSc, plus 40 healthy control subjects.Results
Global methylation in both diseases was significantly lower (<25 %) than in healthy subjects (>30 %, p = 0.0000001). In comparison to healthy controls, a similar gene-specific methylation pattern was observed in both SLE and SSc. Three genes, namely; PRF1, ITGAL and FOXP3 were consistently hypermethylated while CDKN2A and CD70 were hypomethylated in both diseases. The other genes (SOCS1, CTGF, THY1, CXCR4, MT1-G, FLI1, and DNMT1) were generally hypomethylated in SLE whereas they were neither hyper- nor hypo-methylated in SSc.Conclusions
SSc and SLE patients have a higher global hypomethylation than healthy subjects with specific genes being hypomethylated and others hypermethylated. The majority of genes studied were hypomethylated in SLE compared to SSc. In addition to the commonly known hypomethylated genes in SLE and SSc, there are other hypomethylated genes (such as MT-1G and THY-1) that have not previously been investigated in SLE and SSc though are known to be hypermethylated in cancer. 相似文献12.
Austin Chin Chwan Ng Vincent Chow Andy Sze Chiang Yong Tommy Chung Leonard Kritharides 《PloS one》2013,8(4)
Background
Baseline hyponatremia predicts acute mortality following pulmonary embolism (PE). The natural history of serum sodium levels after PE and the relevance to acute and long-term mortality after the PE is unknown.Methods
Clinical details of all patients (n = 1023) admitted to a tertiary institution from 2000–2007 with acute PE were retrieved retrospectively. Serum sodium results from days 1, 3–4, 5–6, and 7 of admission were pre-specified and recorded. We excluded 250 patients without day-1 sodium or had <1 subsequent sodium assessment, leaving 773 patients as the studied cohort. There were 605 patients with normonatremia (sodium≥135 mmol/L throughout admission), 57 with corrected hyponatremia (day-1 sodium<135 mmol/L, then normalized), 54 with acquired hyponatremia and 57 with persistent hyponatremia. Patients’ outcomes were tracked from a state-wide death registry and analyses performed using multivariate-regression modelling.Results
Mean (±standard deviation) day-1 sodium was 138.2±4.3 mmol/L. Total mortality (mean follow-up 3.6±2.5 years) was 38.8% (in-hospital mortality 3.2%). There was no survival difference between studied (n = 773) and excluded (n = 250) patients. Day-1 sodium (adjusted hazard ratio [aHR] 0.89, 95% confidence interval [CI] 0.83–0.95, p = 0.001) predicted in-hospital death. Relative to normonatremia, corrected hyponatremia increased the risk of in-hospital death 3.6-fold (95% CI 1.20–10.9, p = 0.02) and persistent hyponatremia increased the risk 5.6-fold (95% CI 2.08–15.0, p = 0.001). Patients with either persisting or acquired hyponatremia had worse long-term survival than those who had corrected hyponatremia or had been normonatremic throughout (aHR 1.47, 95% CI 1.06–2.03, p = 0.02).Conclusion
Sodium fluctuations after acute PE predict acute and long-term outcome. Factors mediating the correction of hyponatremia following acute PE warrant further investigation. 相似文献13.
Ambika P. Ashraf Jessica A. Alvarez Tanja Dudenbostel David Calhoun Russell Griffin Xudong Wang Lynae J. Hanks Barbara A. Gower 《PloS one》2014,9(12)
Objective
The role of vitamin D in cardiovascular health remains debated as results have been inconsistent. Previous studies have not considered the bioavailability of 25-hydroxy vitamin D [25(OH)D]. Objectives of our study were to investigate the association between serum concentrations of total, free and bioavailable 25(OH)D and independent predictors of cardiovascular risk such as flow mediated dilatation (FMD) and augmentation index (AIx).Design
This cross-sectional study included 47 post-menarchal, adolescent females [31 African American (AA) and 16 European American (EA)].Methods
AIx was standardized to a heart rate of 75 beats/min (AIx75). Free and bioavailable 25(OH)D concentrations were calculated from standard formulas.Results and Conclusions
Mean age of the participants was 15.8±1.4 years and mean body mass index was 23.1±4.0 kg/m2. Serum total 25(OH)D was not associated with FMD, but was positively associated with AIx75 in the adjusted model (rho = 0.4, P = 0.03). AIx75 was positively associated with bioavailable 25(OH)D (rho = 0.4, P = 0.004) and free 25(OH)D (rho = 0.4, P = 0.009) and the associations persisted after adjusting for covariates. In race-specific analyses, total, free and bioavailable 25(OH)D were strongly positively associated with AIx75 in AA (rho = 0.5, 0.4, 0.4, respectively), which persisted even after adjusting for covariates. Whereas in EA there was an inverse association between total 25(OH)D and AIx75 in EA (rho = −0.6), which attenuated after adjusting for covariates.Conclusion
Circulating total, free and bioavailable 25(OH)D were associated with arterial stiffness in adolescent girls, and these associations were race dependent. Notwithstanding, the implications of associations between vascular function indices and 25(OH)D remains unclear. 相似文献14.
Background
The prevalence of obesity is rising. Obesity can lead to cardiovascular and ventilatory complications through multiple mechanisms. Cardiac and pulmonary function in asymptomatic subjects and the effect of structured dietary programs on cardiac and pulmonary function is unclear.Objective
To determine lung and cardiac function in asymptomatic obese adults and to evaluate whether weight loss positively affects functional parameters.Methods
We prospectively evaluated bodyplethysmographic and echocardiographic data in asymptomatic subjects undergoing a structured one-year weight reduction program.Results
74 subjects (32 male, 42 female; mean age 42±12 years) with an average BMI 42.5±7.9, body weight 123.7±24.9 kg were enrolled. Body weight correlated negatively with vital capacity (R = −0.42, p<0.001), FEV1 (R = −0.497, p<0.001) and positively with P 0.1 (R = 0.32, p = 0.02) and myocardial mass (R = 0.419, p = 0.002). After 4 months the study subjects had significantly reduced their body weight (−26.0±11.8 kg) and BMI (−8.9±3.8) associated with a significant improvement of lung function (absolute changes: vital capacity +5.5±7.5% pred., p<0.001; FEV1+9.8±8.3% pred., p<0.001, ITGV+16.4±16.0% pred., p<0.001, SR tot −17.4±41.5% pred., p<0.01). Moreover, P0.1/Pimax decreased to 47.7% (p<0.01) indicating a decreased respiratory load. The change of FEV1 correlated significantly with the change of body weight (R = −0.31, p = 0.03). Echocardiography demonstrated reduced myocardial wall thickness (−0.08±0.2 cm, p = 0.02) and improved left ventricular myocardial performance index (−0.16±0.35, p = 0.02). Mitral annular plane systolic excursion (+0.14, p = 0.03) and pulmonary outflow acceleration time (AT +26.65±41.3 ms, p = 0.001) increased.Conclusion
Even in asymptomatic individuals obesity is associated with abnormalities in pulmonary and cardiac function and increased myocardial mass. All the abnormalities can be reversed by a weight reduction program. 相似文献15.
Paola Palazzo Paola Maggio Riccardo Altavilla Alessandra Di Flaviani Ilaria Giordani Ilaria Malandrucco Fabiana Picconi Francesco Passarelli Patrizio Pasqualetti Matilde Ercolani Fabrizio Vernieri Simona Frontoni 《PloS one》2013,8(12)
Objective
Impaired cerebral vasomotor reactivity (VMR) and flow-mediated dilation (FMD) were found in selected subgroups of type 2 diabetes mellitus (T2DM) patients with long-term disease. Our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled T2DM patients with short-term disease and without cardiac autonomic neuropathy (CAN).Research Design and Methods
Twenty-six T2DM patients with short-term (4.40±4.80 years) and well-controlled (HbA1C = 6.71±1.29%) disease, without any complications, treated with diet and/or metformin, were consecutively recruited. Eighteen controls, comparable by sex and age, were enrolled also.Results
FMD and shear rate FMD were found to be reduced in T2DM subjects with short-term disease (8.5% SD 3.5 and 2.5 SD 1.3, respectively) compared to controls (15.4% SD 4.1 and 3.5 SD 1.4; p<.001 and p<.05). T2DM patients also displayed reduced VMR values than controls (39.4% SD 12.4 vs 51.7%, SD 15.5; p<.05). Sympatho-vagal balance was not different in T2DM patients compared to healthy subjects. FMD and shear rate FMD did not correlate with VMR in T2DM patients or in controls (p>.05).Conclusions
In well-controlled T2DM patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved. 相似文献16.
Purpose
To examine characteristics of ocular hypertensive subjects and potential associations with estimated cerebrospinal fluid pressure (estCSFP).Methods
The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years. Ocular hypertension was defined as intraocular pressure (IOP) >21 mmHg, normal optic nerve head appearance and normal retinal nerve fiber layer thickness. IOP was corrected for its dependence on central corneal thickness (CCT) and corneal curvature radius. Estimated CSFP was calculated as CSFP [mmHg] = 0.44×Body Mass Index [kg/m2]+0.16×Diastolic Blood Pressure [mmHg]−0.18×Age [Years]−1.91. Estimated trans-lamina cribrosa pressure difference (estTLCPD) was IOP–estCSFP.Results
EstCSFP (10.5±3.6 mmHg versus 9.0±3.7 mmHg; P = 0.003) and estTLCPD (12.0±4.4 mmHg versus 5.4±3.8 mmHg; P<0.001) were higher in the ocular hypertensive group than in the normotensive group. In binary regression analysis, ocular hypertension was associated with increased estCSFP (P = 0.03; odds ratio (OR): 1.08; 95% confidence interval (CI): 1.01, 1.17) after adjusting for prevalence of arterial hypertension (P = 0.07; OR: 1.79; 95%CI: 0.96, 3.34), retinal nerve fiber layer thickness (P = 0.03; OR: 0.97; 95%CI: 0.95, 0.997) and blood glucose concentration (P = 0.006; OR: 1.17; 95%CI: 1.04, 1.30).Conclusions
Ocular hypertensive subjects (with IOP correction for CCT and corneal curvature) as compared to ocular normotensive subjects had a significantly higher estCSFP in univariate analysis and in multivariate analysis. Despite of a higher estCSFP, estTLCPD was still markedly higher in ocular hypertensive eyes than in ocular normotensive eyes. 相似文献17.
Jing Wang Yong-Gong Yang Min Zhou Jing-Yan Xu Qi-Guo Zhang Rong-Fu Zhou Bing Chen Jian Ouyang 《PloS one》2013,8(4)
Background
To determine whether the use of idarubicin+cytarabine (IA) is more effective than the use of daunorubicin+cytarabine (DA) as induction chemotherapy for patients with newly diagnosed acute myeloid leukaemia.Methods
A computer-based search was performed. Randomised trials comparing IA with DA as induction therapy for newly diagnosed AML were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival, event-free survival and overall survival); the secondary endpoint was complete remission.Results
Ten trials with 4,060 patients were eligible for this meta-analysis. Our pooled results suggest that IA is associated with a significant advantage in CR (RR = 1·23; 95% CI = 1·07–1·41, p = 0.004), EFS (HR = 0·64; 95% CI = 0·45–0·91, p = 0.013), and OS (HR = 0·88; 95% CI = 0·81–0·95, p = 0.02) but not in DFS (HR = 0·90; 95% CI = 0·80–1·00, p = 0.06). In the subgroup analysis, age had a significant interaction with OS and CR benefits.Conclusion
Our analysis indicated that IA could improve the duration of overall survival compared to DA as induction therapy for young patients with newly diagnosed AML. Further study is needed to determine whether IA can produce clinical benefits in selected genetic or molecular subgroups of young AML patients. 相似文献18.
Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes a considerable burden for the patient and society. It is not clear yet whether aiming for remission (REM) is worthwhile, especially when compared with low disease activity (LDA).Methods
In 356 consecutive RA patients, we obtained data on physical function (health assessment questionnaire (HAQ)), health-related quality of life (HRQoL: Short Form 36 (SF36), Short Form 6 dimensions (SF-6D), Euro QoL 5D (EQ-5D)), work productivity (work productivity and activity impairment questionnaire (WPAI)), as well as estimation of direct and indirect costs. Cross-sectionally, data were compared in patients within different levels of disease activity according to the simplified disease activity index (SDAI; remission (REM ≤3.3); n = 87; low disease activity (LDA: 3.3 < SDAI ≤11); n = 103; moderate to high disease activity (MDA/HDA) >11 n = 119) by using analyses of variance (ANOVA). Longitudinal investigations assessed patients who changed from LDA to REM and vice versa.Results
We found differences in patients achieving REM compared with LDA for HAQ (0.39 ± 0.58 versus 0.72 ± 68), WPAI (percentage impairment while working 11.8% ± 18.7% versus 26.8% ± 23.9%; percentage of overall activity impairment, 10.8% ± 14.1% versus 29.0% ± 23.6%)), EQ-5D (0.89 ± 0.12 versus 0.78 ± 0.6) and SF-36 (physical component score (PCS): 46.0 ± 8.6 versus 38.3 ± 10.5; mental component score (MCS): 49.9 ± 11.1 versus 47.9 ± 12.3) (P < 0.01 for all, except for SF36 MCS). Regarding costs, we found significant differences of direct and indirect costs (P < 0.05) within different levels of disease activity, with higher costs in patients with higher states of disease activity. Longitudinal evaluations confirmed the main analyses.Conclusion
Patients with REM show better function, HRQoL, and productivity, even when compared with another good state, such as LDA. Also from a cost perspective, REM appears superior to all other states. 相似文献19.
Background
Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.Methods
Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO2 = 80%) and hyperoxic (FiO2 = 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (Pdi,tw ) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (Pga,tw ) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.Results
Hypoxia enhanced hyperpnoea-induced Pdi,tw and Pga,tw reductions both immediately after hyperpnoea (Pdi,tw : normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; Pga,tw : normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all P < 0.05) and after 30 min of recovery (Pdi,tw : normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; Pga,tw : normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all P < 0.05). No significant difference in Pdi,tw or Pga,tw reductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.Conclusions
These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O2 transport as during exercise in altitude or in hypoxemic patients. 相似文献20.
Sung Hae Chang Jin Kyun Park Yun Jong Lee Ji Ae Yang Eun Young Lee Yeong Wook Song Eun Bong Lee 《Arthritis research & therapy》2014,16(4)