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Biomedical subjects

P A Komesaroff

Publications and source records attributed to P A Komesaroff.

At least 19 recordsLinked to original sources
PubMed2006

Communication deficiencies in research and monitoring by ethics committees.

AIM: To assess the range of issues that arise for researchers, research participants and ethics committee members in the setting of a hospital-based research environment and to develop a tool that could be used to assist in the process of monitoring. METHODS: A qualitative phase comprising focus group sessions and interviews involving research participants, researchers and ethics committee members of a public teaching hospital and a quantitative phase involving distribution of a questionnaire to research participants and researchers. The data from the qualitative phase were used to assist with the development of the quantitative instrument. Descriptive statistics were derived to describe the various attitudes and practices with respect to the conduct of research. RESULTS: The qualitative study identified issues concerning monitoring procedures and the quality of communication between researchers and study participants. The quantitative analysis showed that parts of the Explanatory Statement (also known as the Participant Information Statement) were incomprehensible to 21% of research participants; the Explanatory Statement was considered too long by 34% of researchers; 6% of researchers believed that explicit consent was not always necessary; of the participants who were out of pocket for attending a study, 53% were offered compensation; and 44% of research participants were unaware of the existence of the ethics committee. In addition, 12% of researchers felt that the quality of monitoring should be improved. CONCLUSIONS: Improvements are necessary in the communication between ethics committees and researchers and research participants, and there is a need for more effective monitoring by ethics committees of research practices. The questionnaire designed for this study could be applied in a prospective manner as a useful tool for monitoring the conduct of research.

Adult↗
PubMed2005

Ethical issues in the relationships with industry: an ongoing challenge. New Guidelines open for public comment.

Interactions between medical practitioners and industry have a profound impact on medical decision-making. It is important to establish clear guidelines to ensure that the values of clinical care, the welfare of society and science prevail over commercial imperatives and monetary values, The Royal Australasian Collage of Physicians has revised its Guidelines for the relationships involving medical practitioners and industry to provide practical assistance to health care professionals in the understanding and management of their interactions with industry. The Guidelines are advisory but provide argument and references to support their conclusions. They outline a practical approach to the management of dualities and conflicts of interests. Among other things, they recommend that gifts should be rejected, including those of small value and entertainment expenses. They argue that industry sponsorship to attend meetings should be restricted to cases where formal contributions are being made, that drug samples should not be accepted from pharmaceutical representatives and that endorsements of specific products and "advertorials" should be avoided. They propose that clinicians should not actively recruit their own patients into studies in which they are investigators and that it should be a condition of agreement to participate by researchers and approval by ethics committees that there is a commitment to make publicly available all results potentially relevant to clinical practice. The Guidelines are intended to reflect changing community attitudes and will continue to be revised from time to time.

Australia↗
PubMed2002

Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2.

Estrogens influence cardiovascular function through direct and indirect effects and via genomic and nongenomic mechanisms. The pathways underlying the nongenomic mechanisms are not completely understood. Estrogen-induced responses in vascular cells have been shown to influence prostaglandins and cyclooxygenase (COX), a key enzyme in the production of prostaglandins, with two isoforms, COX-1 and COX-2. We investigated the effects of prostaglandins on the acute potentiation by 17beta-estradiol (E) of acetylcholine (ACh)-mediated vasodilation in the cutaneous vasculature. Using a double-blind placebo-controlled design, we assessed skin blood flow in 32 healthy, postmenopausal women by laser Doppler velocimetry with direct current iontophoresis of ACh and sodium nitroprusside before and after 6-wk treatment periods with aspirin (a nonspecific COX-1 and COX-2 inhibitor), diclofenac (predominantly a COX-2 inhibitor, which also inhibits COX-1), celecoxib (a specific COX-2 inhibitor), given at anti-inflammatory doses, or placebo. Blood flux values before iontophoresis of ACh did not differ between the treatment groups or after E administration, excluding a direct cutaneous vasodilator effect of the treatments or of E. Acute E administration enhanced the response to ACh after aspirin, diclofenac, and placebo; however, this effect was completely abolished with celecoxib treatment (P < 0.05). E had no effect on sodium nitroprusside-mediated vasodilation after any of the treatments. We conclude that the COX-2 pathway plays a specific role in the rapid E-induced potentiation of cholinergic vasodilation in postmenopausal women.

Acetylcholine↗
PubMed2002

Experiences at menopause of women in a non-English-speaking community: a qualitative study.

CONTEXT: It is important that clinicians appreciate the link between physiological disturbances and cultural meanings. The community surrounding the Baker Medical Research Institute in Melbourne, Australia includes a substantial number of women from a Greek-speaking background who attend the Menopause Clinic. OBJECTIVE: To demonstrate how qualitative methodologies can assist with the development of clinical services by employing them to elucidate the role of cultural variables in the ways in which Greek women view menopause, aging, illness and medicine. DESIGN: This was a qualitative study employing in-depth interviews on five separate occasions over 2 years, analyzed with thematic and ethnographic content analysis. PATIENTS: Subjects were 40 Greek-speaking women attending the Clinic, aged 45-60 years. RESULTS: There is an intricate association between experiences of the menopause and family relationships, problems raised by immigration and the cultural dislocation caused by it, beliefs and theories of the body, religion, and traditional approaches to healing and medicine. Many women had experienced unfavorable or unsatisfactory encounters with medicine in the past, reflecting lack of understanding of the women's experiences and failures of communication about clinical assessments and recommended treatments. Traditional therapies were often used without advising doctors. CONCLUSIONS: The study emphasizes the potential utility of qualitative research methods for improving clinical practice by elaborating the specific requirements of particular groups, and thereby allowing doctors to deliver services that are more acceptable to patients from both a cultural and an ethical point of view, and also more effective. The process established for the evolution of our clinic may serve as a model for other clinics seeking to direct themselves to the needs of particular social groups or communities.

Affect↗
PubMed2001

Is there a future for clinical ethics services in Australia?

Clinical ethics refers to the consideration of ethical issues arising directly in the context of patient care. Health professionals are generally adept at effectively and sensitively managing ethical issues in clinical care. However, in some settings, multidisciplinary clinical ethics services may enhance clinical practice by assisting clinicians, patients and others to identify, understand and manage ethical issues. Clinical ethics services may be particularly valuable for situations in which moral perspectives diverge or communication has deteriorated. Such services may facilitate discussion and help the parties find mutually satisfactory solutions. Clinical ethics services may take various forms, including clinical ethics committees, ethics consultants, patient advocates or other mechanisms for responding to complaints and grievances. There is considerable disagreement about key aspects of clinical ethics services, including who should conduct them, how they should be run and what role they should play in decision-making.

Adult↗
PubMed2001

Estrogen inhibits mechanical strain-induced mitogenesis in human vascular smooth muscle cells via down-regulation of Sp-1.

OBJECTIVE: The cellular basis of the cardioprotective effects of estrogen are largely unknown. An inhibitory effect on vascular smooth muscle (VSM) growth has been proposed. We examined the effect of 17beta-estradiol (E2) on mechanical strain-induced mitogenesis in human fetal VSM cells. METHODS AND RESULTS: Cells were grown on fibronectin-coated plates with silicone-elastomer bottoms, and exposed to cyclic mechanical strain (60 cycles/min), with and without E2 (1 nmol/l), for 48 h. [3H]-Thymidine incorporation was measured during the last 6 h. Strain induced 1.5-2 fold increases in DNA synthesis that were attenuated by antibodies to platelet-derived growth factor (PDGF) AA and BB. Strain also induced increases both in mRNA and protein levels of Sp-1, a transcription factor that binds to the PDGF-A gene promoter site. E2 attenuated strain-induced mitogenesis, and also increases in mRNA and protein levels of Sp-1. The estrogen receptor (ER) antagonist ICI 182,780 (100 nmol/l) reversed the inhibitory effect of E2 on strain-induced increases in DNA synthesis and Sp-1 protein. RT-PCR analysis showed presence of both ER-alpha and -beta in these cells. CONCLUSIONS: Estrogen inhibits strain-induced mitogenesis in human VSM cells via an ER mediated process involving down-regulation of the transcription factor Sp-1.

Cell Culture Techniques↗
PubMed2001

Estrogens and human cardiovascular physiology.

The importance of estrogens for cardiovascular physiology in women is accepted, even if the clinical place for hormonal supplementation after menopause remains uncertain. However, although men produce significant quantities of estrogen, relatively little is known about the role of estrogens in the male cardiovascular system. Recent evidence about the epidemiology of cardiovascular disease, the mechanisms of action of estrogens, the biological actions of endogenously produced estrogens in men, and the acute and chronic effects of estrogens on the vasculature in both men and women, suggests that these hormones may well play an important role in normal male cardiovascular physiology. In addition, they may provide useful adjuncts to therapy in selected groups of men.

Animals↗
PubMed2001

Low-dose estrogen supplementation improves vascular function in hypogonadal men.

It is widely accepted that in women, estrogens provide protection against the development of cardiovascular disease. However, the cardiovascular role of estrogens in men remains uncertain, despite preliminary evidence that endogenous estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating estrogen. We studied the responsiveness of forearm resistance arteries to vasoconstrictor and vasodilator agents in 12 men (mean+/-SEM age, 68.7+/-2.6 years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of estrogen supplementation (estradiol valerate 1 mg daily; n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not affect blood pressure or heart rate. Estrogen supplementation was well tolerated, with no adverse effects. After estrogen treatment, mean estradiol levels increased from <30 to 308+/-65 pmol/L, and both systolic and diastolic blood pressures were reduced. HDL cholesterol levels increased significantly, and vasoconstrictor responses to the NO synthase inhibitor N(G)-monomethyl-L-arginine (1, 2, 4 micromol/min) were enhanced. Vasoconstrictor responses to angiotensin II (8, 16, 32 ng/min) were markedly attenuated by estrogen treatment, as were vasoconstrictor responses to norepinephrine (25, 50, 100 ng/min). Estrogen did not alter the vasodilator responses to acetylcholine (9.25, 18.5, 37 microgram/min) or to the endothelium-independent agent sodium nitroprusside (1.6 microgram/min). Responses to all vasoactive agents were unchanged after administration of placebo. We conclude that low-dose estrogen supplementation in hypogonadal men is well tolerated, lowers blood pressure, and may affect vascular reactivity in a manner that is potentially beneficial, through several mechanisms, including enhancement of basal NO release and attenuation of vasoconstrictor responses to angiotensin II and norepinephrine. These findings suggest the need to consider a possible clinical role for estrogenic compounds in cardiovascular risk reduction in some groups of men.

Acetylcholine↗
PubMed2001

Variations in endothelial function and arterial compliance during the menstrual cycle.

Female sex hormones have been implicated in the cardioprotection of premenopausal women. However, the cardiovascular actions of these hormones and the effects of their natural fluctuations during the menstrual cycle are not fully understood. We studied changes in vascular function during the menstrual cycle in 15 healthy premenopausal women. Four noninvasive procedures were performed during the early follicular (EF), late follicular (LF), early luteal (EL), and late luteal (LL) phases: flow-mediated dilatation (FMD) of the brachial artery during reactive hyperemia, laser Doppler velocimetry (LDV) with direct current iontophoresis of acetylcholine (ACh) and nitroprusside, whole body arterial compliance (WBAC), and pulse wave velocity. Hormone levels were consistent with predicted cycle phase and showed that all subjects ovulated during the cycle studied. FMD, LDV with ACh, and WBAC varied cyclically, with significant increases from the F to LF phase, sharp falls in the EL phase, and significant recoveries in the LL phase. These changes were most marked for FMD [EF, 8.8 +/- 0.6% (mean +/- SEM); LF, 10.0 +/- 0.7; EL, 4.2 +/- 0.6; LL, 8.6 +/- 0.9] and the LDV response to ACh (EF, 2.7 +/- 0.2 V/min; LF, 3.3 +/- 0.4; EL, 1.8 +/- 0.3; LL, 2.7 +/- 0.4). WBAC changed similarly (EF, 0.58 +/- 0.08 arbitrary units; LF, 0.84 +/- 0.06; EL, 0.65 +/- 0.05; LL, 0.68 +/- 0.06). Sodium nitroprusside-induced vasodilatation decreased significantly from EF to EL, with no other significant difference, and pulse wave velocity did not vary significantly over the four time points. Conductance and resistance artery endothelial reactivity and smooth muscle sensitivity to nitric oxide and arterial compliance are modulated significantly in response to the changing hormonal patterns of the menstrual cycle. These findings emphasize the importance of menstrual phase in the interpretation of data on endothelial function and may provide insights into the mechanisms underlying sex differences in cardiovascular risk and other disease processes in premenopausal women.

Adult↗
PubMed2001

Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women.

OBJECTIVES: Many women seek alternatives to hormonal therapies for the management of menopausal symptoms. Among the treatments currently popular are extracts of wild yam (Dioscorea villosa), which are applied topically in the form of a cream. These preparations are known to contain steroidal saponins, including diosgenin, which has been claimed to influence endogenous steroidogenesis. However, there have been no studies of the safety or efficacy of these preparations in the management of menopausal symptoms. METHODS: We therefore conducted a double-blind, placebo-controlled, cross-over study of the effects of a wild yam cream in 23 healthy women suffering from troublesome symptoms of the menopause. After a 4-week baseline period, each woman was given active cream and matching placebo for 3 months in random order. Diaries were completed over the baseline period and for 1 week each month thereafter, and blood and saliva samples were collected at baseline and at 3 and 6 months, for measurement of lipids and hormones. RESULTS: The average age of the subjects was 53.3 +/- 1.1 (SEM) years and average time since last period 4.3 +/- 0.9 years. At baseline, the average body mass index was 27.3 +/- 0.8, cholesterol level 5.7 +/- 0.2 mmol/l and follicle stimulating hormone (FSH) level 74.2 +/- 5.1 IU/l; estradiol levels were undetectable in the majority of cases. After 3 months of treatment, no significant side-effects were reported with either active treatment or placebo, and there were no changes in weight, systolic or diastolic blood pressure, or levels of total serum cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, FSH, glucose, estradiol, or serum or salivary progesterone. Symptom scores showed a minor effect of both placebo and active treatment on diurnal flushing number and severity and total non-flushing symptom scores, and on nocturnal sweating after placebo, but no statistical difference between placebo and active creams. CONCLUSIONS: This study suggests that short-term treatment with topical wild yam extract in women suffering from menopausal symptoms is free of side-effects, but appears to have little effect on menopausal symptoms. It emphasizes the importance of careful study of treatments for menopausal symptoms if women are to be adequately informed about the choices available to them.

Administration, Cutaneous↗