Biomedical subjects

Paul Komesaroff

Publications and source records attributed to Paul Komesaroff.

5 recordsLinked to original sources

PubMed2006

Cellular mechanisms underlying the cardiovascular actions of oestrogens.

Although pre-menopausal women enjoy relative cardiovascular protection, hormone (oestrogen+/-progestin)-replacement therapy has not shown cardiovascular benefits in post-menopausal women, suggesting that the effects of oestrogens on the cardiovascular system are much more complex than previously expected. Endothelial cells, smooth muscle cells, cardiac myocytes and fibroblasts, the cellular components of blood vessels and the heart, play important roles in cardiovascular health and disease. During the development and progression of cardiovascular disease, changes occur both in the structure and function of these cells, resulting in a wide range of abnormalities, which affect growth, death and physiological function. These cells contain functional oestrogen receptors and are targets for oestrogen action. This review focuses on recent studies on the effects of oestrogen on cardiovascular cell function. Oestrogens, particularly 17beta-oestradiol, exert multiple effects on cardiovascular cells, and these effects may contribute to the gender-associated protection against cardiovascular diseases.

Animals↗

PubMed2006

Ideals and compromises in palliative care.

This qualitative study explores the concept of ideal palliative care as it broadens its field of application from terminal care to include people earlier in the course of an illness. Focus groups were held with palliative care professionals from community, inpatient, and hospital consultancy services to examine this issue. Palliative care professionals have clear views of what constitutes ideal care that include: establishing a relationship, setting goals, communication, acceptance, advocacy, flexibility, symptom relief, and recognising the identity of each person. There was agreement upon the nature of obstacles that prevented ideal care being achieved including obstacles created by families, other health professionals, administrative structures, and conflicts between the aims of care for a particular patient. Finally each clinician has a well-developed set of personal views of the acceptable limits to practice, although these views vary widely. The clusters of ideas emerging in this study describe three objects of different ontologic status. The elements of ideal care are conceptual in nature, highlighting the aspirations for workers. The obstacles reflect the real world that palliative care professionals must negotiate each day, giving rise to a form of care that was good enough. The acceptable standards and their limits is the degree to which staff will or will not accept the compromises in care raised by the real world of practice, reflecting the ethical stance of the workers. The pursuit of ideal care may be motivated by a complex mix of aspirations, real-world practicalities and fulfilment for both patients and staff.

Attitude of Health Personnel↗

PubMed2005

Effect of exogenous urotensin-II on vascular tone in skin microcirculation of patients with essential hypertension.

BACKGROUND: Plasma levels of urotensin-II (U-II) have been found to be elevated in patients with essential hypertension. However, the consequence of activation of the U-II system have not been previously determined in these patients. We therefore compared the effect of exogenous U-II administration on vascular tone in hypertensive patients (n = 13) and normotensive subjects (n = 14). METHODS: The effect of U-II on vascular tone was determined in the forearm skin microcirculation using iontophoresis to administer the drug and laser Doppler velocimetry to measure microvascular response. RESULTS: The U-II administration was associated with a dose-dependent vasodilator response from baseline in normotensive subjects (U-II 1 x 10(-12) mol/L, 609 +/- 164; U-II 1 x 10(-9) mol/L, 839 +/- 216; U-II, 1 x 10(-7) mol/L, 1249 +/- 228 arbitrary flux units; P < .0005). A dose-dependent vasoconstrictor response was observed in hypertensive patients compared to baseline (U-II 1 x 10(-12) mol/L, 60 +/- 212; U-II 1 x 10(-9) mol/L, -288 +/- 172; U-II, 1 x 10(-7) mol/L, -607 +/- 165 arbitrary flux units; P < .005). Differences in flow between the two groups were significant at the 1 x 10(-9) mol/L and 1 x 10(-7) mol/L dose levels (P < .001). In contrast, there was no significant difference in flux between baseline and U-II in either group (or between groups) when the opposite polarity was applied. CONCLUSIONS: The demonstration of opposing effects of exogenous U-II in patients with hypertension and normal subjects suggests that U-II may be contributory to the increased vascular tone of these patients.

Acetylcholine↗

PubMed2004

Differential effect of urotensin II on vascular tone in normal subjects and patients with chronic heart failure.

BACKGROUND: Urotensin II (U-II) is a novel vasoactive peptide that also has direct hypertrophic and profibrotic effects on the myocardium. Upregulation of U-II and its receptor has been observed within the heart of patients with chronic heart failure (CHF). Furthermore, plasma levels of U-II have been found to be elevated in some but not all studies in such patients. However, the functional consequences of activation of the U-II system in patients with CHF, assessed by direct administration of exogenous U-II, have not been previously determined. METHODS AND RESULTS: We compared the effect of iontophoresed U-II on skin microvascular tone in normal subjects and patients with CHF, assessed with the use of laser Doppler velocimetry. U-II mediated a dose-dependent vasodilator response in normal subjects (baseline, 137.9+/-52; U-II, 10(-12) mol/L, 145+/-134; U-II, 10(-9) mol/L, 712+/-179; U-II, 10(-7) mol/L, 943+/-139 arbitrary flux units [AFUs], P<0.0001). In contrast, a dose-dependent vasoconstrictor response was observed in patients with CHF (baseline, 336.1+/-129; U-II, 10(-12) mol/L, 317+/-131; U-II, 10(-9) mol/L, 129+/-137; U-II, 10(-7) mol/L, 22.4+/-130 AFUs, P<0.05). Differences in flow between normal subjects and patients with CHF were significant overall (P<0.001, 2-way ANOVA) and at the U-II 10(-9) mol/L and U-II 10(-7) mol/L dose level by Student's unpaired t test (P<0.05, P<0.0001, respectively). In contrast, there was no significant difference between baseline blood flux and any dose of U-II in either group (or between groups) when the opposite polarity was applied. CONCLUSIONS: In addition to direct effects on the myocardium, U-II may contribute to the increased peripheral vascular tone that is characteristic of human CHF. The present observations support the contention that the U-II system may be a potentially important target for pharmacological blockade in the treatment of this condition.

Acetylcholine↗

PubMed2003

Endogenous estrogens influence endothelial function in young men.

Males produce endogenous estrogen from testosterone via the enzyme aromatase. Previous studies have suggested a role for endogenous estrogens in cardiovascular function in men. We examined the effects of endogenous estrogen suppression via aromatase inhibition on endothelial function, systemic arterial compliance, and lipoprotein levels in healthy young men. Using a placebo-controlled double-blind randomized design, 20 healthy men, aged 18 to 32 years, were randomized to receive either the aromatase inhibitor anastrozole (1 mg) or matching placebo. Hormone, lipid levels, C-reactive protein (CRP), and homocysteine were measured. Endothelial function, determined by flow-mediated dilation of the brachial artery, and systemic arterial compliance were assessed at baseline and after 6 weeks of treatment. There was a significant decrease in 17beta-estradiol concentrations with aromatase inhibition, from 85.4+/-4.2 to 64.3+/-8.1 pmol/L (mean+/-SD, P=0.042). Compared with baseline, a significant decrease in flow-mediated dilation was observed in subjects taking anastrozole [median, 6.1% (range, 5.2 to 13.4) to 3.5% (2.0 to 5.7), P=0.034] but not in the placebo group. No changes were observed in nitroglycerin-induced endothelium-independent dilation in either group. There was no change in systemic arterial compliance with either aromatase therapy or placebo. There were no significant changes in lipoproteins, testosterone, DHEA, CRP, or homocysteine levels in either the anastrozole or placebo group. We conclude that suppression of endogenous estrogens with an aromatase inhibitor resulted in impairment of flow-mediated dilation without significant changes in lipoproteins, homocysteine, or CRP. Our results suggest that endogenous estrogens play a direct regulatory role in endothelial function in young healthy men.

Adolescent↗