PubMed Health⌕ Search

Biomedical subjects

D S Celermajer

Publications and source records attributed to D S Celermajer.

At least 19 recordsLinked to original sources
PubMed2003

Clinical criteria and the appropriate use of transthoracic echocardiography for the exclusion of infective endocarditis.

BACKGROUND: Clinical guidelines currently suggest that transthoracic echocardiography (TTE) be carried out in all patients with suspected endocarditis, but the use of TTE where there is a low probability of infective endocarditis has a poor diagnostic yield. This screening approach may no longer be appropriate. OBJECTIVE: To examine whether clinical criteria might aid decision making with respect to the use of TTE in possible endocarditis. DESIGN: A retrospective review of patient records. SETTING: Cardiology department of a tertiary referral centre. PATIENTS: 500 consecutive hospital inpatients referred for TTE to exclude endocarditis. MAIN OUTCOME MEASURES: Evidence of endocardial vegetations on TTE and the presence of predetermined clinical criteria that may predispose to, or be suggestive of, endocarditis. RESULTS: Evidence of infective endocarditis was detected on echocardiography in 43 of the 500 patients (8.6%). In 239 patients (48%), vegetations and certain prespecified clinical criteria were both absent. These criteria were: vasculitic/embolic phenomena; the presence of central venous access; a recent history of injected drug use; presence of a prosthetic valve; and positive blood cultures. The collective absence of these five criteria indicated a zero probability of TTE showing evidence of endocarditis. CONCLUSIONS: The use of simple clinical criteria during the decision making process may avoid many unnecessary TTE examinations in hospital inpatients with a low probability of endocarditis.

Analysis of Variance↗
PubMed2001

Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high-risk children.

BACKGROUND: Autopsy studies in children have shown that atherosclerotic lesions begin to develop first in the intima of the aorta. Recent developments in ultrasound techniques have made it possible to visualize the intima-medial thickness of the abdominal aorta directly (aIMT). Therefore, we examined the feasibility of measuring aIMT in children and studied its value in distinguishing high-risk children from healthy controls compared with a more established marker of subclinical atherosclerosis, the common carotid artery intima-medial thickness (cIMT). METHODS AND RESULTS: IMTs were measured using high-resolution (13 MHz) ultrasound in 88 children (aged 11+/-2 years); 16 had hypercholesterolemia (LDL cholesterol, 5.1+/-1.2 mmol/L), 44 had type 1 diabetes (mean duration, 4.4+/-3.1 years; LDL cholesterol, 2.3+/-0.7 mmol/L), and 28 were healthy (controls; LDL cholesterol, 2.5+/-0.8 mmol/L). High-risk children had significantly increased aIMTs and cIMTs (both P<0.001) compared with controls. In controls, aIMT was similar to cIMT (P=NS), but aIMT was higher than cIMT in the children with hypercholesterolemia and diabetes (both P<0.01). Both markers showed excellent and approximately equal between-observer (<4%) and between-subject variation (<5%). CONCLUSIONS: Children with hypercholesterolemia and diabetes show increased IMTs compared with healthy controls, with a relatively greater increase in the aIMT than in the cIMT. Because atherosclerosis begins first in the intima of the aorta, these data suggest that the aIMT might provide the best currently available noninvasive marker of preclinical atherosclerosis in children.

Adolescent↗
PubMed2001

Evidence-based medicine: how good is the evidence?

The "evidence" in EBM must be of high quality in order to be useful, but this is not always the case. Even the "gold standard" of evidence-based medicine, the randomised clinical trial, is bedevilled by low inclusion rates and potentially important recruitment biases. "Real world" trials often do not give the same results as these highly artificial controlled clinical studies. Meta-analysis, the next most important level of evidence in EBM, may be unreliable, sometimes giving different results to subsequent large randomised trials. There is a bias in the hypotheses tested in large clinical trials, as the costs involved are usually covered by commercially interested companies. For this reason, trials of non-patentable compounds or therapies of no commercial interest may not be performed. The process of journal review and publication is capricious, slow and may have a selection bias towards positive studies, meaning that communication channels for the "evidence" are often unsatisfactory. For many rarer conditions and situations, there is simply no "high level" evidence, such as in paediatrics and subspecialty surgery.

Bias↗
PubMed2001

Impaired vascular responses to nitroglycerin in subjects with coronary atherosclerosis.

To study smooth muscle function in atherosclerosis, we calculated dose-response curves in patients with coronary artery disease and in controls by measuring changes in brachial artery diameter after incremental sublingual doses of nitroglycerin. The doses required to produce a 50% maximal dilator response were significantly higher in patients with coronary artery disease than in controls (p <0.002), suggesting smooth muscle dysfunction in atherosclerosis.

Adult↗
PubMed2001

Androgenic anabolic steroids and arterial structure and function in male bodybuilders.

OBJECTIVES: The study examined arterial and cardiac structure and function in bodybuilders using androgenic anabolic steroids (AAS), compared to non-steroid-using bodybuilder controls. BACKGROUND: Adverse cardiovascular events have been reported in bodybuilders taking anabolic steroids. The cardiovascular effects of AAS, however, have not been investigated in detail. METHODS: We recruited 20 male bodybuilders (aged 35 +/- 3 years), 10 actively using AAS and 10 who denied ever using steroids. Serum lipid and hormone levels, carotid intima-media thickness (IMT), arterial reactivity, and left ventricular (LV) dimensions were measured. Vessel diameter was measured by ultrasound at rest, during reactive hyperemia (an endothelium-dependent response, leading to flow-mediated dilation, FMD), and after sublingual nitroglycerin (GTN, an endothelium-independent dilator). Arterial reactivity was also measured in 10 age-matched non-bodybuilding sedentary controls. RESULTS: Use of AAS was associated with significant decreases in high density lipoprotein cholesterol, sex hormone binding globulin, testosterone and gonadotrophin levels, and significant increases in LV mass and self-reported physical strength (p < 0.05). Carotid IMT (0.60 +/- 0.04 mm vs. 0.63 +/- 0.07 mm), arterial FMD (4.7 +/- 1.4% vs. 4.1 +/- 0.7%) and GTN responses (11.0 +/- 1.9% vs. 14.4 +/- 1.7%) were similar in both bodybuilding groups (p > 0.2). The GTN responses were significantly lower and carotid IMT significantly higher in both bodybuilding groups, however, compared with the non-bodybuilding sedentary controls (p = 0.01). CONCLUSIONS: Although high-level bodybuilding is associated with impaired vascular reactivity and increased arterial thickening, the use of AAS per se is not associated with significant abnormalities of arterial structure or function.

Adult↗
PubMed2001

The Mediterranean score of dietary habits in Chinese populations in four different geographical areas.

OBJECTIVE: To compare the dietary intake of Chinese people living in Pan Yu, Hong Kong, San Francisco and Sydney with respect to cardiovascular health, using the Mediterranean diet score, examining the effects of age, gender, urbanization and acculturation on the diet score. SUBJECTS: A total of 500 men and 510 women in Hong Kong were recruited as a territory-wide stratified random sample. Subjects were recruited in response to local advertisements for the other three sites: Pan Yu, 58 men, 95 women; San Francisco, 166 men, 192 women; Sydney, 95 men, 73 women. METHOD: Food-frequency questionnaire over a 7 week period. A high/healthy score was taken as > or =4 for men and >3 for women, representing a dietary pattern beneficial for cardiovascular health. RESULTS: In Hong Kong, more women in the middle age group (35-54) had a high score than other age groups, and overall more women had high scores than men. In comparing the four geographical regions, Pan Yu had the highest number of subjects with high score, and Hong Kong had the lowest. With the exception of the younger population and men in Hong Kong, the percentage of the population with a high score in all sites is greater than among elderly Greeks consuming a more traditional heart-healthy Mediterranean diet. CONCLUSION: Considerable variations in Chinese dietary patterns exist with respect to age, gender and geographic location. Overall, the Chinese diet is comparable to the Mediterranean diet and may be expected to have similar health benefits that have been documented for the traditional Mediterranean diet.

Adult↗
PubMed2001

Oestradiol improves arterial endothelial function in healthy men receiving testosterone.

OBJECTIVE: To assess prospectively the effects of low dose oestradiol on arterial endothelial and smooth muscle function in healthy men. Oestrogen use is associated with reduced cardiovascular disease in oestrogen-deficient women, however, the vascular effects of low-dose oestradiol in healthy men have not been investigated previously. PATIENTS AND DESIGN: Twenty-three men (aged 32 +/- 8 years) were randomized to receive depot implants of testosterone (T) alone (group 1, n = 10), or T with either 10 mg (group 2, n = 7) or 20 mg (group 3, n = 6) of oestradiol (E). MEASUREMENTS: Hormone levels, lipids and vascular reactivity were measured before, 1 month and 6 months after hormone implantation. Using high-resolution ultrasound, brachial artery diameter was measured at rest, during reactive hyperaemia (leading to flow-mediated dilatation, FMD, which is endothelium-dependent) and after sublingual nitroglycerin (GTN, an endothelium-independent dilator). RESULTS: Oestradiol produced a dose-dependent increase in plasma oestradiol (at 1 month 96 +/- 7, 149 +/- 6, 192 +/- 23 pmol/l in the 3 groups, respectively, P < 0.001 by ANOVA for trend). Minor side-effects (gynaecomastia, nipple tenderness) indicated that 20 mg oestradiol was the maximum tolerated dose. There was also a dose-dependent increase in FMD with oestradiol dose: at 1 month, - 0.2, + 0.2 and + 1.8% for groups 1-3, respectively (P = 0.31 by ANOVA for trend); and at 6 months, - 0.8, + 0.4 and + 2.2% (P = 0.02). The rise in oestradiol levels following treatment correlated with the improvement in FMD (P = 0.01). GTN responses were similar in the 3 groups throughout the study. CONCLUSION: In healthy young men, oestradiol supplementation is associated with enhanced arterial endothelial function, a key marker of vascular health.

Adult↗
PubMed2001

Sex-related differences in the regulation of macrophage cholesterol metabolism.

Men have an earlier onset and higher incidence of coronary heart disease than women, independent of environmental risk factor exposure. As a consequence, there has been considerable interest in the potential role of sex hormones in atherogenesis. An emerging body of evidence suggests that sex-specific tissue and cellular characteristics may mediate sex-specific responses to a variety of stimuli. Recent studies have shown that oestrogen, progesterone and androgens all regulate processes integral to human macrophage foam cell formation, a key event in atherogenesis, in a sex-specific manner; findings that may have important implications for understanding the sex gap in atherosclerosis. Physiological levels of 17beta-estradiol and progesterone are both associated with a female-specific reduction in cholesteryl ester accumulation in human macrophages. By contrast, androgens increase cholesteryl ester formation in male but not in female donor human macrophages. This review summarizes current data concerning the sex-specific effects of sex hormones on processes important to macrophage foam cell formation and the basic mechanisms responsible for the sex specificity of such effects. Future research in this promising field may eventually lead to the novel concept of 'sex-specific' treatments directed at inhibiting atherogenesis.

Adult↗
PubMed2001

A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency.

The efficacy and safety of androgen supplementation in older men remains controversial. Despite biochemical evidence of partial androgen deficiency in older men, controlled studies using T demonstrate equivocal benefits. Furthermore, the importance of aromatization and 5alpha reduction in androgen actions among older men remains unclear. Dihydrotestosterone is the highest potency natural androgen with the additional features that it is neither aromatizable nor susceptible to potency amplification by 5alpha reduction. Therefore, the effects of dihydrotestosterone may differ from those of T in older men. This study evaluated the efficacy and safety of 3 months treatment with transdermal dihydrotestosterone gel on muscle strength, mobility, and quality of life in ambulant, community-dwelling men aged 60 yr or older. Eligible men (plasma T < or =15 nmol/liter) were randomized to undergo daily dermal application of 70 mg dihydrotestosterone gel (n = 18) or vehicle (n = 19) and were studied before, monthly during, and 1 month after treatment. Among 33 (17 dihydrotestosterone, 16 placebo) men completing the study with a high degree of compliance, dihydrotestosterone had significant effects on circulating hormones (increased dihydrotestosterone; decreased total and free testosterone, LH, and FSH; unchanged SHBG and estradiol), lipid profiles (decreased total and low-density lipoprotein cholesterols; unchanged high-density lipoprotein cholesterol and triglycerides), hematopoiesis (increased hemoglobin, hematocrit, and red cell counts), and body composition (decreased skinfold thickness and fat mass; unchanged lean mass and waist to hip ratio). Muscle strength measured by isokinetic peak torque was increased in flexion of the dominant knee but not in knee extension or shoulder contraction, nor was there any significant change in gait, balance, or mobility tests, in cognitive function, or in quality of life scales. Dihydrotestosterone treatment had no adverse effects on prostate (unchanged prostate volumes and prostate-specific antigen) and cardiovascular (no adverse change in vascular reactivity or lipids) safety markers. We conclude that 3 months treatment with transdermal dihydrotestosterone gel demonstrates expected androgenic effects, short-term safety, and limited improvement in lower limb muscle strength but no change in physical functioning or cognitive function.

Administration, Cutaneous↗
PubMed2001

Endothelin-1 plus oxidized low-density lipoprotein, but neither alone, increase human monocyte adhesion to endothelial cells.

Endothelin-1 is a potent vasoconstrictor and mitogenic peptide that is implicated in the atherosclerosis of apolipoprotein E-deficient mice and may promote atherogenesis in humans. We hypothesized that endothelin-1 might promote the adhesion of monocytes to endothelial cells, a key early event in atherosclerosis. We investigated the adhesion of primary human monocytes (isolated by elutriation) to human umbilical vein endothelial cell cultures after incubation with endothelin-1 (0.1 and 0.01 nM; approximately physiological concentrations), copper-oxidized low-density lipoprotein (LDL) (0.1 mg/ml) and a combination of the two. After a 4 h incubation with 0.1 or 0.01 nM endothelin-1 combined with oxidized LDL, adhesion was increased to 120+/-4% (P<0.001 compared with control) and 118+/-4% (P<0.002) respectively, whereas neither substance alone increased adhesion (92-104% of control values; not significant). Neither endothelin receptor A blockade nor co-incubation with anti-fibronectin antibody inhibited the pro-adhesive effects of endothelin-1 plus oxidized LDL (115+/-7% and 115+/-3% of control compared with 120+/-4% respectively; not significant). Endothelial cell expression of intercellular adhesion molecule-1, vascular adhesion molecule-1 and E-selectin were unchanged throughout the experiment. Therefore physiological concentrations of endothelin-1 and oxidized LDL may act synergistically to increase the adhesion of human monocytes to endothelial cells, contributing in part to the observed pro-atherogenic effects of endothelin-1.

Cell Adhesion↗
PubMed2000

Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study.

BACKGROUND: Pulmonary hypertensive crises (PHTC) are a major cause of morbidity and mortality after congenital heart surgery. Inhaled nitric oxide is frequently used as rescue therapy. We did a randomised double-blind study to investigate the role of routinely administered inhaled nitric oxide to prevent pulmonary hypertension in infants at high risk. METHODS: We enrolled 124 infants (64 male, 60 female; median age 3 months [IQR 1-5]), 76% with large ventricular or atrioventricular septal defects, who had high pulmonary flow, pressure, or both, and were undergoing corrective surgery for congenital heart disease. They were randomly assigned continuous low-dose inhaled nitric oxide (n=63) or placebo (n=61) from surgery until just before extubation. We measured the numbers of PHTC, time on study gas, and hours spent in intensive care. Analysis was done by intention to treat. FINDINGS: Compared with placebo, infants receiving inhaled nitric oxide had fewer PHTC (median four [IQR 0-12] vs seven [1-19]; relative risk, unadjusted 0.66, p<0.001, adjusted for dispersion 0.65, p=0.045) and shorter times until criteria for extubation were met (80 [38-121] vs 112 h [63-164], p=0.019). Time taken to wean infants off study gas was 35% longer in the nitric oxide group than in the placebo group (p=0.19), but the total time on the study gas was still 30 h shorter for the nitric oxide group (87 [43-125] vs 117 h [67-168], p=0.023). No important toxic effects arose. INTERPRETATION: In infants at high risk of pulmonary hypertension, routine use of inhaled nitric oxide after congenital heart surgery can lessen the risk of pulmonary hypertensive crises and shorten the postoperative course, with no toxic effects.

Administration, Inhalation↗
PubMed2000

Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women.

Plant estrogen or phytoestrogens (PE) are increasingly consumed for the purposes of menopause symptom relief and prevention of cardiovascular and other diseases. The objective of this study was to evaluate the effects of PE on plasma lipids and lipoproteins and on endothelial function. Twenty healthy, postmenopausal women, 50 to 70 years old, and with evidence of endothelial dysfunction, were treated with a soybean PE tablet of 80 mg/day of isoflavones. Endothelial function was assessed noninvasively using brachial ultrasound. A double-blind, placebo-controlled, randomized crossover design was employed. After 3 weeks stabilization on a standard fat-reduced diet, subjects received PE or placebo for 8 weeks in random order, separated by a washout period of 8 weeks. Compared with placebo, there were no significant effects of PE on blood pressure and plasma lipid or lipoprotein concentrations. Flow-mediated endothelium-dependent dilation (FMD) in response to reactive hyperemia was not significantly changed by PE ingestion (3. 3 +/- 0.7% on placebo vs 4.1 +/- 0.7% on PE, p >0.4). Variation in FMD was not correlated with change in plasma isoflavone concentration (r = -0.09, p >0.7). Glyceryl trinitrate endothelium-independent dilation was not significantly changed with PE (15.9 +/- 1.3% vs 13.7 +/- 1.2%, p >0.1). These results fail to show a significant impact of medium-term supplementation with 80 mg/day of isoflavones on lipid and lipoprotein levels or on endothelial function in healthy, postmenopausal women.

Aged↗
PubMed2000

A comparison of endothelial function in Caucasian and Chinese women before and after the menopause.

OBJECTIVE: Arterial endothelial dysfunction is a key atherogenic event that may be related to oestrogen status. We therefore aimed to compare menopause-related changes in endothelial physiology in Chinese and Caucasian females. METHODS: We studied 40 female subjects; 20 Chinese from a rural region of Southern China (ten premenopausal, aged 20-35 years, and ten postmenopausal, aged 55-66 years), and 20 age-matched Caucasian females from Sydney, Australia. All women had a clinical history, resting blood pressure and fasting lipids measured, and endothelial function assessed. Using high-resolution external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilatation) and after sublingual glyceryl trinitrate (GTW) (an endothelium-independent dilator). RESULTS: There was a significant decline in endothelium-dependent dilatation (EDD) comparing Caucasian females from the premenopausal versus postmenopausal groups (8.4+/-2.7% versus 2.7+/-2.9%; P<0.001). In contrast, there was no significant difference in EDD between pre- and postmenopausal Chinese (9.8+/-3.3% versus 8.3+/-1.7%; P=0.22). On multivariate analysis, postmenopausal status was associated with impaired EDD in Caucasian females (P<0.002) independent of serum cholesterol, blood pressure and vessel size. In contrast, EDD in the Chinese females was not significantly influenced by any of these factors. GTW-induced dilatation was also impaired in the older Caucasian females, a finding explained on multivariate analysis by the increased vessel size in this patient group (P=0.03). CONCLUSION: Menopause is associated with impaired arterial endothelial function in Caucasian but not Chinese women. This suggests possible ethnic differences in menopause-related vascular changes.

Adult↗
PubMed2000

Coenzyme Q improves LDL resistance to ex vivo oxidation but does not enhance endothelial function in hypercholesterolemic young adults.

Oxidative modification of low-density lipoprotein (LDL) may cause arterial endothelial dysfunction in hyperlipidemic subjects. Antioxidants can protect LDL from oxidation and therefore improve endothelial function. Dietary supplementation with coenzyme Q (CoQ(10)) raises its level within LDL, which may subsequently become more resistant to oxidation. Therefore, the aim of this study was to assess whether oral supplementation of CoQ(10) (50 mg three times daily) is effective in reducing ex vivo LDL oxidizability and in improving vascular endothelial function. Twelve nonsmoking healthy adults with hypercholesterolemia (age 34+/-10 years, nine women and three men, total cholesterol 7.4+/-1.1 mmol/l) and endothelial dysfunction (below population mean) at baseline were randomized to receive CoQ(10) or matching placebo in a double-blind crossover study (active/placebo phase 4 weeks, washout 4 weeks). Flow-mediated (FMD, endothelium-dependent) and nitrate-mediated (NMD, smooth muscle-dependent) arterial dilatation were measured by high-resolution ultrasound. CoQ(10) treatment increased plasma CoQ(10) levels from 1.1 +/-0.5 to 5.0+/-2.8 micromol/l (p =.009) but had no significant effect on FMD (4.3+/-2.4 to 5.1+/-3.6 %, p =.99), NMD (21.6+/-6.1 to 20.7+/-7.8 %, p = .38) or serum LDL-cholesterol levels (p = .51). Four subjects were selected randomly for detailed analysis of LDL oxidizability using aqueous peroxyl radicals as the oxidant. In this subgroup, CoQ(10) supplementation significantly increased the time for CoQ(10)H(2) depletion upon oxidant exposure of LDL by 41+/-19 min (p = .04) and decreased the extent of lipid hydroperoxide accumulation after 2 hours by 50+/-37 micromol/l (p =.04). We conclude that dietary supplementation with CoQ(10) decreases ex-vivo LDL oxidizability but has no significant effect on arterial endothelial function in patients with moderate hypercholesterolemia.

Adolescent↗