Hypertension: Wilson A

Anonymous00047, Fitzgerald DA, Massie RJ, Nixon GM, Jaffe A, Wilson A, Landau LI, Twiss J, Smith G, Wainwright C, Harris M. · Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, NSW, Australia. · Med J Aust. · Pubmed #19012558 links to  free full text

Abstract: Chronic neonatal lung disease (CNLD) is defined as a supplemental oxygen requirement beyond 36 weeks' postmenstrual age, with more severely affected infants requiring oxygen beyond a full-term-equivalent age. Low-flow supplemental oxygen facilitates discharge from hospital of infants with CNLD who develop hypoxia in air. There is a lack of data on the most appropriate minimum mean target oxygen saturation (Spo(2)) level. Reflecting a variety of clinical practices and infant comorbidities (frequency of oxygen desaturation, presence of pulmonary hypertension, retinopathy of prematurity, and adequacy of growth), the minimum mean target range for Spo(2) during overnight oximetry should be 93%-95%. The effect of supplemental oxygen on carbon dioxide retention should be considered before deciding on an oxygen flow. Most infants with CNLD are not ready for discharge until their supplemental oxygen requirement is < or = 0.5 litres per minute delivered through a nasal cannula. The safety of short-term disconnection from supplemental oxygen should be assessed before discharge. Assessment of oxygenation during sleep with continuous overnight oximetry or polysomnography is recommended when weaning infants from supplemental oxygen. Discontinuation of oxygen therapy is based on clinical assessments and documentation of adequate oxygenation in room air. There is limited objective evidence on which to base recommendations.

Collins AJ, Couser WG, Dirks JH, Kopple JD, Reiser T, Riella MC, Robinson S, Shah SV, Wilson A. · No affiliation provided · Natl Med J India. · Pubmed #16756188 No free full text.

This publication has no abstract.

Burke V, Beilin LJ, Cutt HE, Mansour J, Wilson A, Mori TA. · University of Western Australia, School of Medicine and Pharmacology, Royal Perth Hospital Unit and West Australian Institute for Medical Research, Perth, Australia. · J Hypertens. · Pubmed #15894901 No free full text.

Abstract: OBJECTIVE: To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals. DESIGN: Randomized controlled trial. SETTING: Research studies unit. PARTICIPANTS: Overweight hypertensive patients, receiving one or two antihypertensive drugs, were recruited by advertising, and allocated randomly to a usual care group (controls; n = 118) or a lifestyle modification group (programme group; n = 123). INTERVENTION: A 4-month programme of weight loss, a low-sodium 'Dietary Approaches to Stop Hypertension'-type diet with added fish, physical activity and moderation of alcohol intake. After 4 months, if mean 24-h ambulatory blood pressure (ABP) was less than 135/85 mmHg, antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun. MAIN OUTCOME MEASURES: Antihypertensive drug requirements, ABP, weight, waist girth at 4 months and 1-year follow-up. RESULTS: Ninety control group and 102 programme group participants completed the study. Mean 24-h ABP changed after 4 months by -1.0/-0.3 +/- 0.5/0.4 mmHg in controls and -4.1/-2.1 +/- 0.7/0.5 mmHg with the lifestyle programme (P < 0.01). At follow-up, changes in the two groups were not significantly different (4.1/1.3 +/- 1.1/1.0 mmHg in controls; 2.5/-0.1 +/- 1.1/0.8 mmHg in the programme group; P = 0.73). At 4 months, drug withdrawal differed significantly between the groups (P = 0.038) in men (control 44%; programme 66%) but not in women (65 and 64%, respectively; P = 0.964). At follow-up, sex-related differences were not significant, and 41% in the control group and 43% in the programme group maintained drug-withdrawal status. With the programme, net weight loss was 3.3 kg (P < 0.001) at 4 months and 3.0 kg (P < 0.001) at follow-up; respective net decreases in waist girth were 3.3 cm (P < 0.001) and 3.5 cm (P < 0.001). CONCLUSIONS: A 4-month multifactorial lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term. Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk.

Whitlock NA, Harrison B, Mixon T, Yu XQ, Wilson A, Gerhardt B, Eberhart DE, Abuin A, Rice DS. · Department of Ophthalmology, Lexicon Pharmaceuticals, The Woodlands, TX 77381, USA. · J Ocul Pharmacol Ther. · Pubmed #19456252 No free full text.

Abstract: PURPOSE: Goals of this study were to determine if pharmacological or genetic inhibition of Rho-associated coiled coil containing protein kinases (known as ROCK1 and ROCK2) alters intraocular pressure (IOP) in mice. METHODS: Micro-cannulation of the anterior chamber was used to measure IOP in wild-type B6.129 hybrid mice following treatment with ROCK inhibitors Y-27632 or Y-39983. For comparative purposes, wild-type mice were also treated with timolol, acetazolamide, pilocarpine, or latanoprost. Mice deficient in either Rock1 or Rock2 were generated by homologous recombination or gene trapping, respectively, and their IOP was determined using identical methods employed in the pharmacology studies. RESULTS: Treatment of wild-type B6.129 hybrid mice with ROCK inhibitors (Y-27632 and Y-39983) resulted in significant reductions in IOP. The magnitude of IOP reduction observed with topical Y-39983 was comparable to timolol, and exceeded the IOP effects of latanoprost in this study. Pilocarpine had no discernible effect on IOP in mice. Moreover, mice deficient in either Rock1 or Rock2 exhibited a significant decrease in IOP compared to their B6.129 wild-type littermates. CONCLUSIONS: Pharmacological or genetic inhibition of ROCKs results in decreased IOP in mice. The magnitude of IOP reduction is significant as demonstrated with comparative pharmacology using agents that lower IOP in humans. These studies support the ROCK pathway as a therapeutic target for treating ocular hypertension.

Burke V, Mansour J, Mori TA, Beilin LJ, Cutt HE, Wilson A. · School of Medicine.harmacology, Royal Perth Hospital Unit and West Australian Institute for Medical Research, University of Western Australia, Perth, WA 6000, Australia. · Health Educ Res. · Pubmed #17483103 links to  free full text

Abstract: Cognitive changes are reported infrequently in programs targeting cardiovascular risk. We examined self-efficacy, behavioral barriers and health beliefs in a lifestyle program for drug-treated hypertensives that aimed to reduce blood pressure, antihypertensive drug needs and cardiovascular risk. In a randomized controlled trial, we compared usual care (controls) and a 4-month program focusing on weight loss, diet and exercise. Outcomes were assessed at baseline, 4 months and 1-year follow-up. Of 241 individuals randomized, 102/123 in the program and 90/118 of controls completed follow-up. In the program group, dietary barriers fell by 14% at 4 months (controls 2%, P = 0.025) and by 8% at follow-up (controls 3%, P = 0.010). Exercise barriers fell by 11% at 4 months (controls 3%, P = 0.020) and 17% (controls 4%, P = 0.002) at follow-up. Dietary self-efficacy improved by 3% at 4 months (controls -1%, P = 0.003) and by 2% at follow-up (controls -1%, P = 0.051). Exercise self-efficacy increased by 8% at 4 months (controls 3%, P < 0.001) and by 5% at follow-up (controls 3%, P = 0.130). Changes in cognitive variables predicted changes in health-related behaviors at 4 months and follow-up. A cognitively based lifestyle program in treated hypertensives is associated with improvements in cognitive measures in the shorter and longer term.

Wang Z, Knight S, Wilson A, Rowley KG, Best JD, McDermott R, Leonard D, Shaw JE, O'Dea K. · The University of Melbourne, Department of Medicine, St Vincent's Hospital, Victoria, Australia. · Eur J Cardiovasc Prev Rehabil. · Pubmed #16926675 No free full text.

Abstract: BACKGROUND: Reliable, large-scale, population-based data on blood pressure for Australian Aboriginal and Torres Strait Islander populations are limited. This present study aims to describe the blood pressure levels and to explore the clinical risk factors for hypertension among Australian Aboriginal and Torres Strait Islander peoples. DESIGN: A cross-sectional population survey was conducted in isolated communities in northern and central Australia. METHODS: Australian Aboriginal people (n = 1088) and Torres Strait Islanders (n = 606) aged 15 years and over were examined between 1993 and 1997. Blood pressure, body mass index, plasma glucose and urinary albumin-creatinine ratio were measured. The association of systolic, diastolic and pulse blood pressure to age was determined and independent associations of hypertension with other clinical variables were tested using logistic regression. Comparisons with results from other Australian data (including AusDiab) were made. RESULTS: Systolic blood pressure and pulse pressure increased in a linear manner with age but mean diastolic blood pressure leveled off at around 50 years and decreased thereafter, suggestive of arterial stiffening. The age-standardized prevalence of hypertension (blood pressure > or = 140/90 mmHg or medication) for subjects aged 25-54 years was 27%, compared with 9% in non-Indigenous Australians in the Northern Territory and Queensland (AusDiab Survey). Older age, male sex, higher body mass index, albumin-creatinine ratio and diabetes were independently associated with hypertension. CONCLUSIONS: Elevated blood pressure is a public health concern for indigenous people, which again highlights health differentials in Australia. Early detection and management of high blood pressure should be assigned a high priority in Indigenous communities.

Wokhlu N, Hsu VM, Wilson A, Moreyra AE, Shindler D. · Division of Cardiology, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA. · J Electrocardiol. · Pubmed #16919671 No free full text.

Abstract: BACKGROUND AND PURPOSE: Scleroderma is an immune-mediated disease characterized by excess deposition of collagen leading to microvascular occlusion. Morbidity and mortality are often secondary to pulmonary hypertension from injury to pulmonary microvasculature and interstitial lung disease. This study correlated P-wave findings on the 12-lead electrocardiogram (ECG) with mean pulmonary artery pressure (mPAP) measured by right heart catheterization in patients with scleroderma. METHODS: A retrospective review of 12-lead ECGs in 23 patients referred to a rheumatology clinic with the diagnosis of scleroderma was performed. Right heart catheterization was performed within 1 month of the resting ECG. RESULTS: Linear regression related P-wave amplitude in lead II with mPAP (r = 0.52, P = .011) This model was 73% sensitive and 67% specific for the presence or absence of elevated mPAP. CONCLUSIONS: P-wave amplitude analysis on the ECG may be helpful in the assessment of pulmonary hypertension in patients with scleroderma.

Summar ML, Hall L, Christman B, Barr F, Smith H, Kallianpur A, Brown N, Yadav M, Willis A, Eeds A, Cermak E, Summar S, Wilson A, Arvin M, Putnam A, Wills M, Cunningham G. · Division of Medical Genetics, Department of Pediatrics and Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. · Mol Genet Metab. · Pubmed #15050969 No free full text.

Abstract: Carbamyl phosphate synthetase I (CPSI) determines the rate-limiting entry of free ammonia into the urea cycle. Disruption of CPSI affects the liver's ability to remove waste nitrogen and produce arginine, citrulline, and urea. Arginine is the necessary precursor for the critical biomolecule, nitric oxide (NO). We have studied the classic model of CPSI deficiency, which results in severe hyperammonemia, and identified a large number of molecular defects. A number of CPSI polymorphisms have been found that appear to result in functional consequences. We have examined the association of these polymorphisms with various environmental stress conditions and found that certain CPSI alleles are associated with clinical outcome. We refer to these associations as environmentally determined genetic expression (EDGE) affects. In addition to studies of classic CPSI deficiency, we have developed data for the EDGE concept in post-cardiac surgery-related pulmonary hypertension, hepatic veno-occlusive disease after bone marrow transplantation, and persistent pulmonary hypertension of the newborn. We have linked these outcomes and genotypes to the availability of the urea cycle intermediates, citrulline and arginine, and their role in NO synthesis. We hypothesize that these polymorphisms affect the functional efficiency of CPSI and thus the entire urea cycle and as such, the availability of the NO substrates. By piecing together the various functional aspects of the urea cycle changes we have seen, we can better understand the clinical vulnerabilities of patients in environmentally stressful situations. This knowledge should allow us to design intervention strategies to either predict or modify the associated adverse outcomes.

Burke V, Mori TA, Giangiulio N, Gillam HF, Beilin LJ, Houghton S, Cutt HE, Mansour J, Wilson A. · Western Australian Institute for Medical Research, HeartSearch and University of Western Australia, Department of Medicine, Royal Perth Hospital, Perth, Western Australia, Australia. · Asia Pac J Clin Nutr. · Pubmed #12492652 No free full text.

Abstract: Health-related behaviours affecting diet, weight control and physical activity are important for long-term cardiovascular health but behaviour change is difficult to initiate and even more difficult to maintain. We have developed a health promotion program, in which social support has a key role, to encourage a prudent diet, weight control and physical activity. Behaviour change is based on evaluating initial behaviour, weighing up costs and benefits, assessing barriers to change and goal-setting. We first evaluated the program in couples beginning to live together, a group chosen because of the risk of weight gain and decreased physical activity after marriage, readiness to change behaviour at that time in the life course and the opportunity to use partner's support in achieving behaviour change. In an initial short-term study with 39 couples, intake of fat and take-away foods decreased and consumption of fruit, vegetables and reduced fat foods increased. Physical activity increased and there was a 6% fall in blood cholesterol. Further evaluation in 137 couples included assessment after 12 months. A decrease in fat intake and increase in physical activity and fitness seen at the end of the program persisted 1 year later. Lower cholesterol and a trend to lower weight gain and lower blood pressure were also maintained after 12 months. We have modified the program aiming for weight loss, improved dietary habits and increased physical activity in overweight treated hypertensives, supported by their partners. Decreased intake of energy, total and saturated fat, and weight loss seen at the end of the 16 week program was significantly greater in the intervention group than with usual care. Blood pressure fell in the program group at the end of intervention and, in men, withdrawal of antihypertensive drugs was significantly associated with the intervention. Weight loss and a decrease in waist circumference were maintained in the program group up to 16 months after entering the study. This program has the potential for wider application in other at-risk groups.

Ma Z, Mi Z, Wilson A, Alber S, Robbins PD, Watkins S, Pitt B, Li S. · Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA. · Gene Ther. · Pubmed #11859420 links to  free full text

Abstract: Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have proven to be limited for pulmonary gene transfer with respect to efficiency, in part because of difficulty in assuring significant residence time in the lung and/or paucity of receptors for adenovirus on the endothelium. A recent study has shown that the use of a bispecific antibody to endothelial cells and Ad vectors efficiently redirects Ad vectors to pulmonary endothelium and improves gene expression in the lung. In this study, we report that pulmonary gene transfer by Ad vectors can also be improved significantly via the use of cationic liposomes. Preinjection of cationic liposomes followed by adenovirus led to a significant increase in the level of gene expression in the lung. The improvement in pulmonary gene transfer was associated with a decrease in the level of gene expression in the liver. Gene expression in the lung lasted for up to 2 weeks. This protocol, together with genetic modification of adenovirus, may prove to be useful for pulmonary gene transfer for the treatment of pulmonary diseases. This method may also be extended to pulmonary gene transfer using other types of viral vectors via vascular route.