Biomedical subjects

Sharon Wallace

Publications and source records attributed to Sharon Wallace.

9 recordsLinked to original sources

PubMed2006

Endothelial function is associated with pulse pressure, pulse wave velocity, and augmentation index in healthy humans.

Arterial stiffness is an independent predictor of mortality and is regulated by a number of factors, including vascular smooth muscle tone. However, the relationship between endothelial function and definitive measures of arterial stiffness and wave reflections has not been described in healthy individuals. Therefore, we tested the hypothesis that endothelial function is inversely correlated with aortic pulse wave velocity (PWV), central pulse pressure, and augmentation index in healthy individuals. Peripheral and central pulse pressure and augmentation index were determined at rest, and global endothelial function was measured using pulse wave analysis and administration of sublingual nitroglycerin and inhaled albuterol. Aortic PWV was also determined at baseline in a subset of 89 subjects. In a separate group of subjects (n=89), aortic PWV was measured and brachial artery flow-mediated dilatation assessed as a measure of conduit artery endothelial function. Global endothelial function was significantly and inversely correlated with aortic PWV (r=-0.69; P<0.001), augmentation index (r=-0.59; P<0.001), and central (r=-0.34; P<0.001) and peripheral pulse pressure (r=-0.15; P=0.03). Moreover, there was a stronger correlation between central rather than peripheral pulse pressure. After adjusting for potential confounders, global endothelial function remained independently and inversely associated with aortic PWV and augmentation index. There was also a significant, inverse relationship between conduit artery endothelial function and aortic PWV (r=0.39, P<0.001), which remained independent after adjusting for confounding factors. In healthy individuals, a decline in endothelial function is associated with increased large artery stiffness, wave reflections, and central pulse pressure.

Administration, Inhalation↗

PubMed2006

Variation in the human matrix metalloproteinase-9 gene is associated with arterial stiffness in healthy individuals.

BACKGROUND: Arterial stiffness is an important determinant of cardiovascular risk. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes including serine proteases and matrix metalloproteinases (MMPs). Serum MMP-9 levels correlate with arterial stiffness and predict cardiovascular risk. Polymorphisms in the MMP-9 gene are also associated with large artery function in subjects with coronary artery disease. Therefore, we investigated the influence of known MMP-9 (-1562C>T, R279Q) polymorphisms on arterial stiffness in a large cohort of healthy individuals (n=865). METHODS AND RESULTS: Aortic pulse wave velocity (PWV) and augmentation index were assessed. Supine blood pressure, biochemical markers, MMP-9 levels, and serum elastase activity (SEA) were also determined. Genomic DNA was extracted and genotyping performed. Aortic PWV, serum MMP-9, and SEA were higher in carriers of the rare alleles for the -1562C>T and R279Q polymorphisms. These polymorphisms were also associated with aortic PWV after correction for other confounding factors. Stepwise regression models with known or likely determinants of arterial stiffness revealed that approximately 60% of the variability in aortic PWV was attributable to age, mean arterial pressure, and genetic variants (P<0.001). CONCLUSIONS: We have demonstrated for the first time that aortic stiffness and elastase activity are influenced by MMP-9 gene polymorphisms. This suggests that the genetic variation in this protein may be involved in the process of large artery stiffening.

Adult↗

PubMed2005

Systemic Acyl-CoA:cholesterol acyltransferase inhibition reduces inflammation and improves vascular function in hypercholesterolemia.

BACKGROUND: Circulating lipids may initiate and progress atherosclerosis by causing vascular inflammation. Monocytes and tissue macrophages are involved and regulate lipid metabolism in the vascular wall through acetylation of cholesterol by acyl-CoA:cholesterol acyltransferase (ACAT). ACAT inhibition reduces atherosclerosis in animal models by mechanisms that may be independent of their effects on circulating lipids. Because endothelial dysfunction is an important factor in atherosclerosis, we tested the hypothesis that systemic ACAT inhibition would improve endothelial function in hypercholesterolemic humans and assessed its effects on circulating lipids and markers of systemic inflammation. METHODS AND RESULTS: We studied 21 hypercholesterolemic subjects in a double-blind, randomized-crossover, placebo-controlled trial with assessments of circulating lipids, markers of inflammation, resistance-vessel endothelial function (with venous occlusion plethysmography), and conduit-vessel vasoreactivity (brachial artery flow-mediated dilation at baseline and after placebo or treatment with avasimibe 750 mg QDS for 8 weeks. There was a small change in total cholesterol with treatment (326+/-25 to 311+/-22 mg/dL, P=0.04). Circulating tumor necrosis factor-alpha was significantly reduced (4.0+/-0.3 to 3.6+/-0.2 pg/mL, P=0.02); resistance vessel responses to acetylcholine, bradykinin, and verapamil were significantly enhanced; and responses to nitroglycerin and conduit-vessel vasoreactivity were unchanged after ACAT inhibition. CONCLUSIONS: Systemic ACAT inhibition reduces circulating tumor necrosis factor-alpha levels in hypercholesterolemic subjects and improves resistance-vessel endothelial function, with small effects on circulating cholesterol. This may be a novel therapeutic strategy to target vascular inflammation and endothelial dysfunction in atherosclerosis.

Acyl Coenzyme A↗

PubMed2005

Superficial cervico-vaginal myofibroblastoma: a report of five cases.

AIMS: To describe the pathological and immunohistochemical features of five cases of superficial cervico-vaginal myofibroblastoma (SCVM), a recently described mesenchymal tumour affecting middle-aged and elderly females. METHODS: The histological features of five cases of SCVM arising in four patients were reviewed including one case which recurred locally 9 years after initial excision biopsy. All cases were immunostained using the streptavidin-biotin technique using antisera to vimentin, smooth muscle actin, desmin, S100 protein, cytokeratin, h-caldesmon, calponin, CD99, CD117 (c-kit), bcl-2, oestrogen receptor and progesterone receptor. RESULTS: The patients were aged from 40 to 71 years (mean 55.2 years). The tumours were situated within the vagina (four cases) and cervix (one case) and ranged from 16 to 45 mm in greatest dimension. One patient had two separate vaginal SCVM. The tumours were characterised by uniform spindle and stellate-shaped cells separated by a collagenous or myxoid stroma. No mitotic activity was identified. Characteristically the tumours were well circumscribed and separated from the surface epithelium by a rim of normal stroma. The initial and recurrent tumours in one patient were similar except for increased stromal collagen in the recurrence. All tumours were immunoreactive for vimentin, desmin, CD34, CD99, bcl-2, calponin and hormone receptors while two tumours showed focal smooth muscle actin expression. There was no expression of S100 protein, h-caldesmon, CD117 or cytokeratin. CONCLUSIONS: SCVM appears to be a relatively distinct lesion although there is some histological and immunophenotypical overlap with other mesenchymal tumours, particularly fibroepithelial polyp, leiomyoma and solitary fibrous tumour. As local recurrence developed 9 years after intial treatment in one patient, long-term clinical follow-up would seem appropriate.

Adult↗

PubMed2005

Increased stroke volume and aortic stiffness contribute to isolated systolic hypertension in young adults.

Isolated systolic hypertension is a common condition in individuals aged older than 60 years. However, isolated systolic hypertension has also been described in young individuals, although the mechanisms are poorly understood. We hypothesized that in young adults, isolated systolic hypertension and essential hypertension have different hemodynamic mechanisms and the aim of this study was to test this hypothesis in a cohort of subjects from The ENIGMA Study. Peripheral and central blood pressure, aortic pulse wave velocity, cardiac output, stroke volume, and peripheral vascular resistance were determined in 1008 subjects, aged 17 to 27 years. Compared with normotensive subjects, those with isolated systolic hypertension had significantly higher peripheral, central, and mean blood pressure, aortic pulse wave velocity, cardiac output, and stroke volume (P<0.001 for all comparisons). However, there were no differences in pulse pressure amplification, heart rate, or peripheral vascular resistance between the two groups. Compared with subjects with essential hypertension, mean pressure, heart rate, and peripheral vascular resistance were all significantly lower in isolated systolic hypertensive subjects, but pulse pressure amplification, aortic pulse wave velocity, cardiac output, and stroke volume were higher (P<0.001 for all comparisons). We have demonstrated that in young adults, isolated systolic hypertension and essential hypertension arise from different hemodynamic mechanisms. Isolated systolic hypertension appears to result from an increased stroke volume and/or aortic stiffness, whereas the major hemodynamic abnormality underlying essential hypertension is an increased peripheral vascular resistance. Long-term follow-up of these individuals is now required to determine whether they are at increased risk compared with age-matched normotensive individuals.

Adolescent↗

PubMed2004

Matrix metalloproteinase-9 (MMP-9), MMP-2, and serum elastase activity are associated with systolic hypertension and arterial stiffness.

BACKGROUND: Arterial stiffness is an independent determinant of cardiovascular risk, and arterial stiffening is the predominant abnormality in systolic hypertension. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes, including matrix metalloproteinase-9 (MMP-9) and MMP-2. We hypothesized that elastase activity would be related to arterial stiffness and tested this using isolated systolic hypertension (ISH) as a model of stiffening and separately in a large cohort of healthy individuals. METHODS AND RESULTS: A total of 116 subjects with ISH and 114 matched controls, as well as 447 individuals free from cardiovascular disease were studied. Aortic and brachial pulse wave velocity (PWV) and augmentation index were determined. Blood pressure, lipids, C-reactive protein, MMP-9, MMP-2, serum elastase activity (SEA), and tissue-specific inhibitor 2 of metalloproteinases were measured. Aortic and brachial PWV, MMP-9, MMP-2, and SEA levels were increased in ISH subjects compared with controls (P=0.001). MMP-9 levels correlated linearly and significantly with aortic (r=0.45; P=0.001) and brachial PWV (r=0.22; P=0.002), even after adjustments for confounding variables. In the younger, healthy subjects, MMP-9 and SEA were also independently associated with aortic PWV. CONCLUSIONS: Aortic stiffness is related to MMP-9 levels and SEA, not only in ISH, but also in younger, apparently healthy individuals. This suggests that elastases including MMP-9 may be involved in the process of arterial stiffening and development of ISH. The relationship between arterial stiffness and elastase activity was examined in isolated systolic hypertension (ISH), and separately in a large cohort of healthy individuals. Aortic stiffness is related to MMP-9, not only in ISH, but also in healthy individuals, suggesting elastases may be involved in the process of arterial stiffening and the development of ISH.

Aged↗

PubMed2004

C-reactive protein is associated with arterial stiffness in apparently healthy individuals.

OBJECTIVE: C-reactive protein (CRP) levels predict outcome in healthy individuals and patients with atherosclerosis. Arterial stiffness also independently predicts all-cause and cardiovascular mortality and may be involved in the process of atherosclerosis. The aim of this study was to investigate the relationship between stiffness and inflammation in a cohort of healthy individuals. METHODS AND RESULTS: Pulse wave velocity (PWV) and blood pressure were assessed in 427 individuals. Subjects with cardiovascular disease, diabetes, hypercholesterolemia and those using medication were excluded. CRP correlated with age, mean arterial pressure (MAP), brachial and aortic PWV, and pulse pressures. In multiple regression models, aortic PWV correlated independently with age, CRP, male gender, and MAP (R2=0.593; P<0.001). CRP was also independently associated with brachial PWV. Aortic augmentation index correlated with age, gender, MAP, and inversely with heart rate and height, but not with CRP (R2=0.794; P<0.001). Aortic, carotid, and brachial pulse pressures were also independently associated with CRP levels. CONCLUSIONS: Aortic and brachial PWV, and pulse pressure, relate to levels of inflammation in healthy individuals, suggesting that inflammation may be involved in arterial stiffening. Anti-inflammatory strategies may, therefore, be of benefit in reducing arterial stiffness and thus cardiovascular risk, especially in patients with premature arterial stiffening.

Adolescent↗

PubMed2003

Ambulatory blood pressure, left ventricular mass, and conduit artery function late after successful repair of coarctation of the aorta.

OBJECTIVES: We sought to evaluate the determinants of hypertension during daily life and left ventricular (LV) hypertrophy in patients with successfully repaired coarctation of the aorta (CoA), as well as their relationship to abnormalities of arterial function. BACKGROUND: Arterial hypertension may recur late after repair of CoA, which is related to a more adverse outcome. Furthermore, patients with normal resting blood pressure (BP) may have hypertension during daily life and LV hypertrophy. The determinants of these two adverse prognostic factors have not been investigated. METHODS: We studied 72 patients (9 to 58 years of age) who underwent coarctation repair at age 0.1 to 480 months (42 [60%] at <1 year) and had been followed up for 155 +/- 76 months. They underwent ambulatory BP monitoring, echocardiography for LV mass, studies of brachial artery responses to flow (i.e., flow-mediated dilation [FMD]) and glyceryl trinitrate (GTN), and determination of pulse wave velocity (PWV) and measures of arterial reactivity and stiffness. Findings were compared with those of 53 healthy volunteers. RESULTS: Patients had higher 24-h systolic BP and LV mass than controls. Both endothelium-dependent FMD and the response to the smooth muscle dilator GTN were reduced, and PWV was increased. There was a negative independent correlation between GTN response and 24-h systolic BP in both patients and control subjects. Systolic BP at 24 h was an independent predictor of LV mass, having an accentuated impact in coarctation subjects as compared with controls. CONCLUSIONS: In patients with repaired coarctation, reduced vascular reactivity is associated with hypertension during daily life and with increased LV mass, both of which are important predictors for late morbidity and mortality.

Activities of Daily Living↗

PubMed2003

Teaching baccalaureate nursing students to prevent medication errors using a problem-based learning approach.

An objective of the baccalaureate nursing curriculum at Thomas Jefferson University, Jefferson College of Health Professions is to facilitate nursing students' transfer of medication error knowledge into preventive action in the clinical unit. Using a problem-based learning approach, first-semester students are exposed to situations that reflect the real-world scope and complexity of medication administration and errors. Using the frameworks of Failure Mode Analysis and Human Error Mode and Effects Analysis, student groups identify hypotheses, devise solutions, and develop continuous quality improvement processes to prevent errors and facilitate error reporting. Problem-based learning is used in subsequent clinical experiences throughout the curriculum. This reinforcement, combined with a focus on increasingly complex pharmacological agents and medication calculations, enables students to employ critical thinking skills and develop the confidence necessary for safe, professional practice.

Attitude of Health Personnel↗