Cell transplantation preserves matrix homeostasis: A novel paracrine mechanism

ObjectivesCell transplantation prevents chamber dilatation, but the underlying molecular mechanisms remain undefined. Structural cardiac remodeling involves matrix degradation from an imbalance of matrix metalloproteinases (MMP) relative to endogenous tissue inhibitors of metalloproteinases (TIMP). We aimed to determine the capacity of cell transplantation to alter extracellular matrix in the failing heart and, in so doing, identify novel paracrine molecular mediators underlying the beneficial effects of cell transplantation on chamber dilatation.MethodsSmooth muscle cells were transplanted to the dilating left ventricle of cardiomyopathic hamsters (CTX, n = 15) compared with age-matched media-injected cardiomyopathic (CON, n = 15) and normal hamsters (n = 7). After 5 weeks, left ventricular volume was measured by computerized planimetry. Fibrillar collagen was examined by confocal microscopy. Matrix homeostasis was quantified by measuring MMP/TIMP expression/activity relative to myocardial collagen synthesis (14C-proline uptake).ResultsLeft ventricular dilatation was attenuated in CTX hearts (P = .02). CTX restored perimysial collagen fiber content and architecture to normal levels. TIMP-2 and TIMP-3 expression were enhanced in CTX (TIMP-2, 195% ± 42% of CON, P = .02; TIMP-3, 118% ± 3% of CON, P = .002), and correspondingly, gelatinase MMP-2 activity was reduced (P < .05). The TIMP:MMP ratio was increased in CTX hearts (TIMP-2 to MMP-2, 410% ± 134% of CON, P = .04, and TIMP-3 to MMP-9, 205% ± 47% of CON, P = .03), reflecting a reduced capacity for matrix degradation. Collagen synthesis was equivalent (CTX vs CON), suggesting that restored matrix architecture was a function of attenuated matrix degradation.ConclusionsThese data provide the first evidence that cell transplantation limits ventricular dilatation in the failing heart through a paracrine-mediated mechanism that preserves extracellular matrix homeostasis

Stenting of venous bypass grafts: A new treatment modality for patients who are poor candidates for reintervention

Abstract During a 2-year period, 136 self-expanding Wall-stents were implanted in saphenous vein bypass grafts in 69 patients with end-stage coronary artery disease. All patients had severe symptoms and the majority were poor candidates for either repeat surgery or conventional bypass coronary angioplasty because of unfavorable native anatomy, impaired left ventricular function, or a high-risk bypass lesion anatomy for coronary angioplasty. All procedures were technically successful without major complications and a need for emergency bypass surgery. However, during the hospital stay acute thrombotic complications occurred in seven patients (10%) resulting in one death and acute myocardial infarction in five patients and necessitating emergency repeat PTCA in two patients and repeat CABG in four. Twenty-three patients had serious hemorrhagic complications directly related to the rigorous anticoagulation schedule. Two patients died of fatal cerebral bleeding. During follow-up, another five patients died accounting for a total mortality rate of 12%. At late angiographic follow-up (4.9 ± 3.4 months, n = 53), 25 patients (47%) had a restenosis (≥50% DS) within or immediately adjacent to the stent, necessitating reintervention in 19 patients (PTCA, n = 12; repeat CABG, n = 7). In the group without stent-related restenosis (n = 28), 15 patients had progression of disease in either the native or bypass vessels leading to recurrence of major anginal symptoms within 1 to 24 months. Ten of these patients required further intervention (stent, n = 6; PTCA, n = 3; repeat CABG, n = 1). Stenting in saphenous coronary bypass grafts can be performed safely with excellent immediate angiographic and clinical results. Early occlusion, late restenosis, and bleeding complications associated with the aggressive anticoagulant treatment remain significant limitations. Reintervention as a result of restenosis or progression of disease in other lesions is common. Stenting of diseased bypass grafts in symptomatic patients with end-stage coronary artery disease (who are at high risk for conventional angioplasty or surgical reintervention) may be useful as palliative therapy

Return to work of breast cancer survivors: a systematic review of intervention studies

<p>Abstract</p> <p>Background</p> <p>Breast cancer management has improved dramatically in the past three decades and as a result, a population of working age women is breast cancer survivor. Interventions for breast cancer survivors have shown improvements in quality of life and in physical and psychological states. In contrast, efforts aimed at stimulating re-employment and return-to-work interventions for breast cancer survivors have not kept pace. The objective of this review was to study the effects and characteristics of intervention studies on breast cancer survivors in which the outcome was return to work.</p> <p>Methods</p> <p>The Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2006), Medline, Ovid, EMBASE and PsychInfo were systematically searched for studies conducted between 1970 to February 2007. Intervention studies for female breast cancer survivors that were focused on return to work were included.</p> <p>Results</p> <p>Our search strategy identified 5219 studies. Four studies out of 100 potentially relevant abstracts were selected and included 46–317 employed women who had had mastectomy, adjuvant therapy and rehabilitation, with the outcome return to work. The intervention programs focused on improvement of physical, psychological and social recovery. Although a substantial percentage (between 75% to 85%) of patients included in these studies returned to work after rehabilitation, it is not clear whether this proportion would have been lower for patients without counseling or exercise, or any other interventions, as three out of four studies did not include a comparison group.</p> <p>Conclusion</p> <p>The most important finding of this review is the lack of methodologically sound intervention studies on breast cancer survivors with the outcome return to work. Using evidence from qualitative and observational studies on cancer and the good results of intervention studies on return to work programs and vocational rehabilitation, return to work interventions for breast cancer survivors should be further developed and evaluated.</p

The use of insulin declines as patients live farther from their source of care: results of a survey of adults with type 2 diabetes

BACKGROUND: Although most diabetic patients do not achieve good physiologic control, patients who live closer to their source of primary care tend to have better glycemic control than those who live farther away. We sought to assess the role of travel burden as a barrier to the use of insulin in adults with diabetes METHODS: 781 adults receiving primary care for type 2 diabetes were recruited from the Vermont Diabetes Information System. They completed postal surveys and were interviewed at home. Travel burden was estimated as the shortest possible driving distance from the patient's home to the site of primary care. Medication use, age, sex, race, marital status, education, health insurance, duration of diabetes, and frequency of care were self-reported. Body mass index was measured by a trained field interviewer. Glycemic control was measured by the glycosolated hemoglobin A1C assay. RESULTS: Driving distance was significantly associated with insulin use, controlling for the covariates and potential confounders. The odds ratio for using insulin associated with each kilometer of driving distance was 0.97 (95% confidence interval 0.95, 0.99; P = 0.01). The odds ratio for using insulin for those living within 10 km (compared to those with greater driving distances) was 2.29 (1.35, 3.88; P = 0.02). DISCUSSION: Adults with type 2 diabetes who live farther from their source of primary care are significantly less likely to use insulin. This association is not due to confounding by age, sex, race, education, income, health insurance, body mass index, duration of diabetes, use of oral agents, glycemic control, or frequency of care, and may be responsible for the poorer physiologic control noted among patients with greater travel burdens