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Dong-Chuan Guo,
Christina L Papke,
Van Tran-Fadulu,
Ellen S Regalado,
Nili Avidan,
Ralph Jay Johnson,
Dong H Kim,
Hariyadarshi Pannu,
Marcia C Willing,
Elizabeth Sparks, [......],
Sudha Veeraraghavan,
Donna M Muzny,
David A Wheeler,
James T Willerson,
Robert K Yu,
Sanjay S Shete,
Steven E Scherer,
C S Raman,
L Maximilian Buja,
Dianna M Milewicz
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ABSTRACT: The vascular smooth muscle cell (SMC)-specific isoform of alpha-actin (ACTA2) is a major component of the contractile apparatus in SMCs located throughout the arterial system. Heterozygous ACTA2 mutations cause familial thoracic aortic aneurysms and dissections (TAAD), but only half of mutation carriers have aortic disease. Linkage analysis and association studies of individuals in 20 families with ACTA2 mutations indicate that mutation carriers can have a diversity of vascular diseases, including premature onset of coronary artery disease (CAD) and premature ischemic strokes (including Moyamoya disease [MMD]), as well as previously defined TAAD. Sequencing of DNA from patients with nonfamilial TAAD and from premature-onset CAD patients independently identified ACTA2 mutations in these patients and premature onset strokes in family members with ACTA2 mutations. Vascular pathology and analysis of explanted SMCs and myofibroblasts from patients harboring ACTA2 suggested that increased proliferation of SMCs contributed to occlusive diseases. These results indicate that heterozygous ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, including TAAD, premature CAD, ischemic strokes, and MMD. These data demonstrate that diffuse vascular diseases resulting from either occluded or enlarged arteries can be caused by mutations in a single gene and have direct implications for clinical management and research on familial vascular diseases.
The American Journal of Human Genetics 06/2009; 84(5):617-27. · 10.60 Impact Factor
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ABSTRACT: The incidence of heart failure (HF) is increasing as the population ages. Pharmacotherapy is an important component of treatment and yields significant improvements in survival and quality of life. In recent decades, exercise has gradually become accepted as an intervention beneficial to patients with HF, but more information is needed to clarify the effects of exercise and optimize interventions. Therefore, a systematic review of randomized controlled trials published from 1966 to October 2006 was carried out via PubMed. About 69 trials were reviewed, which used as main outcome measures: (a) central hemodynamic parameters, (b) peripheral blood flow, (c) endothelial function, (d) activation of neurohormones and cytokine systems, (e) structure of and metabolism in skeletal muscles, and/or (f) quality of life. Study findings suggest that the favorable physiological responses to exercise might slow some of the pathophysiological progression of HF. However, most of the trials reviewed here were based on relatively small samples and selected participant groups, and the exercise programs varied widely. These limitations and inconsistencies need to be addressed through further studies. Furthermore, reliable strategies for maintaining the positive effects of exercise and extending them to patients' daily life and quality of life are scarce in these trials. These domains need further exploration through rationally designed, large-scale randomized controlled trials.
Biological Research for Nursing 11/2008; 10(2):156-82. · 1.28 Impact Factor
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ABSTRACT: The aim of this study was to assess understanding of genetics and attitudes towards genetic testing for clinical and research purposes in a group of older adults in the UK.
Increasingly, genomics will have an impact on the diagnosis, prevention and treatment of common diseases and the prescription of drugs. The chance of being affected by a medical condition increases with age and therefore the use of genetic testing as part of general health-care practice has an impact on the older population.
Older adults were recruited to two focus groups (n=7 and n=10 respectively). Focus group discussions were guided by a series of questions and were audiotaped. The transcribed data were coded for significant statements, which were organized under thematic headings.
The mean age of participants was 76 years. The main themes to emerge were: understanding, approach to genetic testing and conditions for testing. In this cohort, the older adults were largely unsure about the underlying scientific basis of genetics but were keen to learn more. While enhanced medical knowledge could enable preventive measures to be taken and so reduce suffering, it was acknowledged that for some people knowing the future could potentially cause anxiety and harm. Participants were wary about research being used to benefit private companies and voiced ethical concerns about potential coercion to be tested and the misuse of science. However, all participants had an altruistic approach that influenced their willingness to be tested to benefit others in their family or the wider community. Conditions for testing included provision of information about the purpose of testing and feedback on the results.
Older adults are positive about the opportunities presented by genetic testing for clinical reasons and research, but need accurate information about the reasons for and implications of such testing.
The results of this study confirm the need for nurses to be proactive in developing the genetic competencies required to detect potential familial disease, make appropriate referrals to genetic services and ensure informed consent is obtained for genetic testing.
Journal of Clinical Nursing 06/2006; 15(5):565-73. · 1.12 Impact Factor
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ABSTRACT: Although coronary heart disease (CHD) is traditionally viewed as a disease predominantly of males, it is the number one cause of death among American women. Half of all CHD deaths occur in women, and death within the first few years of initial myocardial infarction is significantly higher in women. Few women, however, perceive a significant health risk from heart disease. The dramatic decline in CHD mortality from lifestyle modification suggests that environmental factors play a significant role in genetic expression. Family-focused nursing care affects generations of family members and can significantly reduce morbidity and mortality from CHD.
Journal of Obstetric Gynecologic & Neonatal Nursing 31(2):217-28. · 1.03 Impact Factor
