BackgroundWe compared physical functioning, mental health, and quality of life (QoL) of patients with different subtypes of congenital heart disease (CHD) in a large international sample and investigated the role of functional class in explaining the variance in outcomes across heart defects.MethodsIn the cross-sectional Assessment of Patterns of Patient-Reported Outcome in Adults with Congenital Heart Disease-International Study (APPROACH-IS), we enrolled 4028 adult patients with CHD from 15 countries. Diagnostic groups with at least 50 patients were included in these analyses, yielding a sample of 3538 patients (median age: 32 years; 52% women). Physical functioning, mental health, and QoL were measured with the SF-12 health status survey, Hospital Anxiety and Depression Scale (HADS), linear analog scale (LAS) and Satisfaction with Life Scale, respectively. Functional class was assessed using the patient-reported New York Heart Association (NYHA) class. Multivariable general linear mixed models were applied to assess the relationship between the type of CHD and patient-reported outcomes, adjusted for patient characteristics, and with country as random effect.ResultsPatients with coarctation of the aorta and those with isolated aortic valve disease reported the best physical functioning, mental health, and QoL. Patients with cyanotic heart disease or Eisenmenger syndrome had worst outcomes. The differences were statistically significant, above and beyond other patient characteristics. However, the explained variances were small (0.6% to 4.1%) and decreased further when functional status was added to the models (0.4% to 0.9%).ConclusionsSome types of CHD predict worse patient-reported outcomes. However, it appears that it is the functional status associated with the heart defect rather than the heart defect itself that shapes the outcomes. 相似文献
Lung cancer is one of the most common causes of death in elderly patients in the United States. Treatment advances have improved survival in selected patients. The available treatments carry the risk of morbidity and mortality but the benefit in most patients far outweighs the risks, given the dismal prognosis of untreated disease. Elderly patients with lung cancer need careful attention during pretreatment assessment. Advanced age alone, however, should not contraindicate aggressive treatment. In the high-risk groups it is important to involve a team of physicians including surgeons, radiation oncologists, medical oncologists, and pulmonologists, who are familiar with current treatment options and their risks. 相似文献
Platelets and their granular contents influence both angiogenesis and breast cancer progression. This study was performed to assess the effect of breast cancer and its treatment on platelet biology and the response to inhibition of the platelet P2Y12 receptor. Receptor-specific platelet activation and inhibition was studied for three platelet-associated proteins important in cancer angiogenesis and progression, vascular endothelial growth factor (VEGF), thrombospondin1 (TSP1), and transforming growth factor beta 1 (TGF-β1).
Twenty-four women with active breast cancer and 10 healthy controls not receiving antiplatelet therapy participated in the study. Ex vivo activation of platelets in whole blood was accomplished using PAR1AP, PAR4AP, convulxin, and ADP. Platelet inhibition was accomplished using the P2Y12 receptor antagonist cangrelor (the in vitro equivalent of clopidogrel). VEGF, TSP1, and TGF-β1 were measured using standard ELISA.
Platelet activation by ADP, PAR1, PAR4, and collagen receptors increased VEGF, TSP1, and TGF-β1 secretion in patients with breast cancer. Agonist-induced release of VEGF was greater in cancer patients as compared to healthy controls (p = 0.02 for ADP, p < 0.001 for PAR1AP, PAR4AP, and convulxin) despite a decrease in the efficiency of VEGF secretion in patients with breast cancer. These differences were not observed for TSP1 and TGF-β1 secretion. P2Y12 receptor inhibition decreased VEGF, TSP1, and TGF-β1 secretion. In patients with cancer, cangrelor inhibited TSP1 release to a greater extent than VEGF and TGF-β1 release. In patients with breast cancer, the magnitude of platelet inhibition achieved by cangrelor was greater than that achieved with healthy controls for all agonists and platelet proteins studied.
While platelets are known to influence progression of breast cancer, our results show that breast cancer and its treatment influence the platelet phenotype by increasing the secretion of pro-angiogenic proteins following platelet activation, modulating the efficiency of platelet protein release as well as increasing the response to antiplatelet therapy. 相似文献
The optimal medium for cardiac differentiation of adult primitive cells remains to be established. We quantitatively compared
the efficacy of IGF-1, dynorphin B, insulin, oxytocin, bFGF, and TGF-β1 in inducing cardiomyogenic differentiation. Adult
mouse skeletal muscle-derived Sca1+/CD45-/c-kit-/Thy-1+ (SM+) and Sca1-/CD45-/c-kit-/Thy-1+ (SM-) cells were cultured in basic
medium (BM; DMEM, FBS, IGF-1, dynorphin B) alone and BM supplemented with insulin, oxytocin, bFGF, or TGF-β1. Cardiac differentiation
was evaluated by the expression of cardiac-specific markers at the mRNA (qRT-PCR) and protein (immunocytochemistry) levels.
BM+TGF-β1 upregulated mRNA expression of Nkx2.5 and GATA-4 after 4 days and Myl2 after 9 days. After 30 days, BM+TGF-β1 induced the greatest extent of cardiac differentiation (by morphology
and expression of cardiac markers) in SM- cells. We conclude that TGF-β1 enhances cardiomyogenic differentiation in skeletal
muscle-derived adult primitive cells. This strategy may be utilized to induce cardiac differentiation as well as to examine
the cardiomyogenic potential of adult tissue-derived stem/progenitor cells.
Electronic supplementary material The online version of this article (DOI:) contains supplementary material, which is available to authorized users.
Returned for 1. Revision: 8 January 2008 1. Revision received: 8 April 2008
Ahmed Abdel-Latif and Ewa K. Zuba-Surma contributed equally to this work. 相似文献
The apical sodium-dependent bile acid transporter (Asbt) is responsible for transport across the intestinal brush border membrane; however, the carrier(s) responsible for basolateral bile acid export into the portal circulation remains to be determined. Although the heteromeric organic solute transporter Ostalpha-Ostbeta exhibits many properties predicted for a candidate intestinal basolateral bile acid transporter, the in vivo functions of Ostalpha-Ostbeta have not been investigated. To determine the role of Ostalpha-Ostbeta in intestinal bile acid absorption, the Ostalpha gene was disrupted by homologous recombination in mice. Ostalpha(-/-) mice were physically indistinguishable from wild-type mice. In everted gut sac experiments, transileal transport of taurocholate was reduced by >80% in Ostalpha(-/-) vs. wild-type mice; the residual taurocholate transport was further reduced to near-background levels in gut sacs prepared from Ostalpha(-/-)Mrp3(-/-) mice. The bile acid pool size was significantly reduced (>65%) in Ostalpha(-/-) mice, but fecal bile acid excretion was not elevated. The decreased pool size in Ostalpha(-/-) mice resulted from reduced hepatic Cyp7a1 expression that was inversely correlated with ileal expression of fibroblast growth factor 15 (FGF15). These data indicate that Ostalpha-Ostbeta is essential for intestinal bile acid transport in mice. Unlike a block in intestinal apical bile acid uptake, genetic ablation of basolateral bile acid export disrupts the classical homeostatic control of hepatic bile acid biosynthesis. 相似文献
To ensure its growth and prosperity, general internal medicine will need to embrace care of the elderly, research on aging, and geriatrics education as components of its core mission. Experts agree that general internal medicine fellows could benefit from increased opportunities in research on aging and geriatrics education; however, important barriers will hamper efforts to integrate geriatrics training into general internal medicine fellowship programs. This article reviews the barriers to integration and proposes solutions for overcoming those barriers. As a result of interviews and meetings with a broad representation of general internists, geriatricians, funding agencies, and policymakers, we propose 2 interventions: 1) the development of institutional program grants to foster collaboration between general internal medicine and geriatrics faculty in the training of general internal medicine fellows and 2) the creation of a 3-year fellowship program combining general internal medicine and geriatrics. This article discusses the importance of evaluating these and other programs intended to increase the geriatrics experience of general internal medicine fellows, and it describes the potential implications of these changes for a broad array of stakeholder institutions. 相似文献