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Gene therapy for coronary disease.

Gene transfer offers an approach to the study and treatment of coronary disease. The localized nature of vascular diseases like restenosis has made the application of genetic material an attractive therapeutic option. Viral and non viral vectors have been developed to facilitate the entry of foreign DNA into cells. Vector improvement and production, demonstration of vector safety and therapeutic efficacy are among the main present challenges. Therapeutic angiogenesis using gene transfer is a new strategy for the treatment of coronary disease. This approach is currently being investigated in clinical trials in patients with coronary diseases. Other potential targets for genetic treatment in cardiovascular diseases include thrombosis, reendothelialization, and extracellular matrix synthesis.

Animals↗

Propagation of infiltrating lymphocytes and graft coronary disease in cardiac transplant recipients.

The pattern of lymphocyte growth from endomyocardial biopsies in 55 heart transplant recipients was shown to be correlated with the subsequent development of graft coronary disease. Persistent lymphocyte growth was observed in 39 patients, and 15 of these growers (or 41%) developed graft coronary disease. In contrast, only 1 of 15 patients (or 6%) with nongrower biopsies showed subsequent graft coronary disease. Thus, biopsy growth was associated with a higher incidence of subsequent GCD (p = 0.02). A comparison between the group of 15 growers with subsequent graft coronary disease and the 24 growers without subsequent graft coronary disease did not show any differences with respect to patient age, presence of coronary artery disease in the native heart, biopsy histology, donor alloreactivity of biopsy grown lymphocytes, and immunosuppressive drug regimen. On the other hand, the number of treated rejection episodes was significantly lower in the grower group with subsequent graft coronary disease (p = 0.04). These data support the concept that graft coronary disease may involve rejection and that more immunosuppression may lower its incidence. This concept is strengthened by findings showing that alloreactive T cells can be propagated from coronary arteries of cardiac allografts with graft coronary disease.

Biopsy↗

[Exercise-nitroglycerine technetium-99m-2-methoxy isobutyl isonitrile tomoscintigraphic imaging for identifying diseased coronary vessels: comparison with thallium-201 standard exercise-redistribution study].

A same-day double injection protocol employing 99mTc-methoxy isobutyl isonitrile (MIBI) and myocardial single-photon emission computed tomography (SPECT) for detecting coronary heart disease (CAD) was assessed in 21 patients. Our exercise-nitroglycerin (NTG) MIBI study was performed as follows: 150 MBq 99mTc-MIBI was injected at peak exercise, and after 5 minutes 0.3 mg of NTG was sublingually administered. Then, SPECT was performed 1 hour later. Immediately after the 1st imaging, patients were injected of 750 MBq 99mTc-MIBI and were reimaged 1 hour later. Within 1 month, all patients were underwent standard exercise redistribution SPECT thallium (Tl) study. Of the 126 myocardial segments evaluated, 81 were judged as normal by both techniques, while the presence of stress defects were demonstrated in 37 segments (Agreement: 94%). Vessel sensitivities were 75% by MIBI and 67% by Tl. Specificities were 90% by MIBI and 93% by Tl. For the pattern of reversibility in myocardial segments with stress defects, the agreement was 73%. In conclusion, our exercise-NTG MIBI may be safely performed, giving results equivalent to those of standard stress-redistribution thallium studies.

Angina Pectoris↗

Usefulness of exercise myocardial scintigraphy in multivessel coronary disease after incomplete revascularization with coronary stenting.

The aim of this prospective study was to evaluate the prognostic value of exercise myocardial scintigraphy in patients who undergo incomplete revascularization with percutaneous coronary stenting. In 322 consecutive patients (mean age 61 +/- 10 years), exercise technetium-99m-tetrofosmin single-photon emission computed tomography scintigraphy was prospectively performed 4 to 6 months after an incomplete revascularization procedure. Follow-up lasted < or = 84 months (median 33). Patients with normal findings were at low risk of cardiac events compared with patients with mildly abnormal and severely abnormal findings (yearly event rate 1.5% vs 5.1% and 8.5%, respectively, p < 0.01). A significant difference was observed in hard, soft, and composite event-free survival among patients with normal, mildly abnormal, and severely abnormal findings (p < 0.01, p < 0.03, and p < 0.01, respectively). Nuclear data provided significant incremental prognostic value for cardiac events compared with the clinical, angiographic, and exercise test findings. In conclusion, in patients with incomplete revascularization procedures, exercise myocardial scintigraphy provides significant independent information concerning the subsequent risk of cardiac events, with an annualized event rate of < 2% for patients with normal scan findings. Myocardial scintigraphy is able to provide incremental prognostic information after adjusting for clinical, angiographic, and exercise variables.

Aged↗

Insulin resistance, chronic inflammatory state and the link with systemic lupus erythematosus-related coronary disease.

The association of SLE with atherosclerosis suggests a common pathogenic mechanism. SLE and atherosclerosis are immune complex-mediated diseases. The integration of metabolism and immunity, which under normal conditions is beneficial for the maintenance of good health, can become deteriorative under conditions of metabolic challenge, as exemplified by the immunosuppression characteristic of malnourished or starving individuals. It is now apparent that obesity is associated with a state of chronic inflammation, particularly in white adipose tissue. However, in the absence of obesity, infusion of animals with inflammatory cytokines or lipids can cause insulin resistance. It is possible that the stresses of obesity are similar enough to the stresses of an infection and the body reacts to obesity as it would to an infection. Atherosclerosis can be considered to have a significant chronic inflammatory component. Inflammation also contributes to the typical dyslipidemia associated with SLE that is characterized by elevations of VLDL, LDL and triglycerides as well as reduced HDL. The link between insulin resistance and SLE can be explained by the chronic inflammatory state, and the consequent dyslipoproteinemia.

Chronic Disease↗