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Biomedical subjects

A Dart

Publications and source records attributed to A Dart.

At least 19 recordsLinked to original sources

A randomised controlled trial of omega-3 fatty acid supplementation for the treatment of hypertriglyceridemia in HIV-infected males on highly active antiretroviral therapy.

BACKGROUND: Hypertriglyceridaemia is a recognised metabolic abnormality in HIV-infected people, increasing in severity in people treated with highly active antiretroviral therapy (HAART). An alternative treatment for hypertriglyceridaemia in non-HIV-infected populations is omega-3 fatty acid supplementation. This study aimed to compare the effectiveness of omega-3 fatty acid supplementation and placebo in lowering fasting triglyceride levels in HIV-infected patients on HAART. METHODS: A placebo-controlled, randomised, double-blind trial in participants on stable HAART with fasting triglycerides of >3.5 mm to 10.0 mm using 9 g of omega-3 fatty acids versus placebo (olive oil) after a 6-week lead in on dietary therapy. RESULTS: Eleven patients were enrolled. The mean triglyceride level for the population decreased from 5.02 mm at baseline to 4.44 mm (-11.6%) after dietary intervention and 3.37 mm (-32.9%) after the 8-week treatment period. In the omega-3 fatty acid arm of the study, triglycerides fell from 5.34 mm to 5.02 mm (-6%) after dietary intervention and to 2.30 mm (-56.9%) after the treatment period. In the placebo arm of the study, triglycerides fell from 4.77 mm to 4.05 mm (-15.1%) after dietary intervention and to 4.08 mm (-14.5%) after the treatment period. Using the random effects model, a statistically significant effect on triglycerides of omega-3 fatty acid versus placebo was found (chi(2) = 6.04, P = 0.0487). The estimated difference between groups for change in mean triglycerides over 8 weeks was -2.32 mm (95% CI -4.52, -0.12 mm). CONCLUSIONS: Omega-3 fatty acids are likely to be an effective treatment for hypertriglyceridaemia in HIV-infected males on HAART.

Adult↗

Simvastatin improves arterial compliance in the lower limb but not in the aorta.

UNLABELLED: Several cardiovascular risk factors adversely affect arterial compliance or the distensibility of large arteries. The role of raised low-density lipoproteins (LDL) cholesterol is uncertain, most studies having shown little effect. We, therefore, investigated whether lowering LDL would improve arterial compliance. Twenty hypercholesterolemic subjects (LDL cholesterol 4.95+/-1.11 mmol/l) were randomized to simvastatin (20 or 40 mg daily) or placebo, each for 4 weeks. Arterial function was assessed at the end of the placebo and simvastatin periods, systemic arterial compliance (SAC) and pulse wave velocities (PWV) centrally (aorto-femoral) and peripherally (femoral-posterior tibial). RESULTS: Lipoproteins (LDL) cholesterol was reduced similarly with 20 and 40 mg simvastatin (ten subjects each dose) and data were pooled. Lipoproteins (LDL) cholesterol fell 39%, plasma triglyceride fell 18% and high-density lipoprotein (HDL) cholesterol rose 12%, all significant. Systemic arterial compliance (SAC) and central PWV did not change significantly but peripheral PWV showed evidence of greater compliance after simvastatin (10.1+/-1.3 vs. 9.4+/-1.3 m/s with placebo and simvastatin, P<0.03), distensibility being inversely related to PWV. Improvement in PWV was greatest in those with poorest baseline values, r=0.50; P<0.02. CONCLUSION: Peripheral PWV was alone improved with LDL lowering probably because of the muscularity of that arterial bed; central PWV and SAC (in the elastic aorta) were not influenced.

Anticholesteremic Agents↗

The effect of three different doses of sodium pentosan polysulphate on haematological and haemostatic variables in adult horses.

OBJECTIVE: To evaluate the effects of three different doses of sodium pentosan polysulphate (PPS) on haematological and haemostatic variables in adult horses. DESIGN: Eight adult standardbred horses were used. All horses received a single injection of 0, 3, 6, and 10 mg/kg of PPS at the beginning of each treatment week for 4 weeks so that by the end of the study all horses had received all four doses of PPS. Blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 168 h after each weekly injection of PPS. Variables measured were packed cell volume, haemoglobin, red blood cell count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelet count, white cell count, neutrophil count, lymphocyte count, eosinophil count, monocyte count, serum protein, fibrinogen, prothrombin time, and activated partial thromboplastin time (PTT). Data were analysed using an ANOVA. Significance was set at P < 0.05. RESULTS: There was a dose-dependent increase in PTT. A significant increase in PTT occurrred in all treatment groups when compared to horses receiving 0 mg/kg in which there was no change over time. The PTT values all returned to baseline by 48 h after treatment. The mean neutrophil count was higher 3 h after treatment when compared to time 0. Horses receiving 3 mg/kg of PPS had a higher lymphocyte count 4 h after injection, and those receiving 6 and 10 mg/kg had higher counts at 3,4,6 and 8 h after injection when compared to time 0. At 8 h after injection horses receiving 6 and 10 mg PPS had higher lymphocyte counts than horses not receiving PPS. CONCLUSIONS: PPS causes a dose-dependent prolongation of PTT in horses. At the dose rates currently recommended for treatment of joint problems in horses this increase was small and remained elevated from baseline for up to 24 h. Based on these findings doses of PPS up to 3 mg/kg should not be administered to horses within 24 h of high stress activities or where physical injury may occur.

Animals↗

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↗

Age-related deterioration in arterial structure and function in postmenopausal women: impact of hormone replacement therapy.

Epidemiological evidence suggests that hormone replacement therapy (HRT) reduces morbidity and mortality from cardiovascular diseases in postmenopausal women. In this study, indices of arterial function [total systemic arterial compliance (SAC) and carotid arterial distensibility coefficient (DC)], structure [carotid intima-media thickness (IMT)], and lipid profiles were compared in postmenopausal women on long-term HRT and aged-matched controls. One hundred nine women aged 44 to 77 years taking HRT and an age-matched group of 108 female controls were entered into the study. The two groups were similar for body mass index, smoking status, exercise level, alcohol intake, and blood pressure. Fasting cholesterol, low density lipoprotein, and lipoprotein(a) were reduced and high density lipoprotein increased in the HRT group. IMT increased with age; SAC and DC were reduced with age in both groups. The HRT group had a higher mean SAC (0.42+/-0.02 versus 0.34+/-0.02 U/mm Hg, P=0.0001) and a lower mean IMT (0.67+/-0.01 versus 0.74+/-0.02 mm, P=0.006) than did controls. Subgroup analysis for estrogen versus estrogen plus progestin revealed no differences for SAC and IMT; DC, however, was greater in estrogen-only users. Smokers on HRT had a higher mean SAC (0.41+/-0.02 versus 0.31+/-0.01 U/mm Hg, P=0.008) and a lower IMT (0.65+/-0.02 versus 0.75+/-0.03 mm, P=0.002) than did smokers not taking such therapy. A protective effect of long-term estrogen therapy on age-related changes in arterial structure and function in postmenopausal women was evident in smokers and nonsmokers alike. Progestin appeared to counteract the effects of estrogen on carotid compliance only. Long-term controlled trials are needed to determine the significance of these findings.

Adult↗

A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia.

We directly compared the safety and efficacy of atorvastatin and simvastatin in hypercholesterolemic patients. This 1-year, randomized, double-blind study was performed at 9 community- and university-based research hospitals in Australia. One-hundred seventy-seven patients between the ages of 18 and 80 years with baseline low-density-lipoprotein (LDL) cholesterol > or = 4.14 and < or = 7.76 mmol/L (160 and 300 mg/dl, respectively) and triglycerides < or = 4.52 mmol/L (400 mg/dl) received once-daily dosing with atorvastatin (Lipitor) 10 mg or simvastatin (Zocor) 10 mg. At week 16, the dose of medication was titrated to atorvastatin 20 mg or simvastatin 20 mg if patients did not meet LDL cholesterol target of < or = 3.36 mmol/L (130 mg/dl). Efficacy was reported as percent change from baseline in LDL cholesterol, total cholesterol, very low density lipoprotein cholesterol, total triglycerides, high-density lipoprotein cholesterol, apolipoproteins AI and B, and lipoprotein(a). Atorvastatin caused significantly greater reductions from baseline than did simvastatin for LDL cholesterol, total cholesterol, very low density lipoprotein cholesterol, triglycerides, and apolipoprotein B (p <0.05). No patient in either treatment group had clinically important elevations in creatine phosphokinase, alanine aminotransaminase, or aspartate aminotransaminase. No serious adverse events were considered associated with treatment. With atorvastatin 10 mg, 46% of the patients achieved LDL cholesterol target goal by week 16, whereas only 27% of the simvastatin patients achieved the target goal at the 10-mg dose. This cholesterol-lowering profile affords utility in many patient types.

Adult↗

Influence of apo E phenotype on postprandial triglyceride and glucose responses in subjects with and without coronary heart disease.

Apolipoprotein E phenotypes and fasting lipid and other biochemical parameters were determined in 51 patients with recently diagnosed coronary heart disease (CHD) and 164 control subjects. The age of the participants was 62.5 +/- 6.6 (S.D.) and 63% were male. Forty-eight CHD cases and 51 control subjects were also studied for 8 h after a fat-rich meal. Apo E phenotypes did not differ significantly between CHD cases and control subjects although there was a tendency for under-representation of E2/E3 in the cases (6% versus 16%). Fifteen CHD cases and 37 (of 164) control subjects had at least one epsilon 4 allele. Fasting plasma triglyceride concentrations were not different between CHD cases and controls but were significantly elevated in subjects with an epsilon 4 allele. CHD cases did, however, have a significantly elevated fasting insulin compared with controls. Postprandial triglyceride responses were not different between CHD cases and controls. However, postprandial triglyceride responses were elevated in subjects (CHD cases and controls) who had an epsilon 4 allele. In multivariate analysis, both epsilon 4 allele status and body mass index (BMI) were significant determinants of postprandial triglyceride responses. Postprandial glucose responses were also elevated in subjects with an epsilon 4 allele. When comparison of CHD cases and controls was restricted to those without an epsilon 4 allele, CHD cases showed a borderline significant (P = 0.05) difference in time course from controls, with a slower decline in plasma triglyceride from the peak response. Fasting and postprandial triglyceride and postprandial glucose responses are strongly dependent on the presence of an epsilon 4 allele. The elevation in postprandial triglyceride responses associated with an epsilon 4 allele can obscure differences associated with the presence of CHD and suggests that although elevated postprandial triglyceride response may be a risk factor for CHD, it is not the major reason for the association between the possession of an epsilon 4 allele and coronary disease.

Aged↗

Effects of oestrogen and progesterone on age-related changes in arteries of postmenopausal women.

1. Hormone replacement therapy (HRT) with oestrogen or oestrogen plus progestin may have different effects on arterial structure and function. To examine this question, carotid artery intima-medial thickness (IMT) and indices of systemic and carotid arterial compliance were measured in groups of older men, postmenopausal women not on HRT (non-HRT) and those women on long-term HRT with oestrogen alone (HRT-E) or oestrogen plus progestin (HRT-EP). 2. Sixty men, 90 postmenopausal women taking HRT and 91 not taking HRT participated in the study. The groups were similar for age, body mass index, numbers of smokers, physical activity, alcohol intake and blood pressure. 3. Plasma total cholesterol was reduced and high-density lipoprotein-cholesterol was increased in the HRT group compared with the non-HRT group; low-density lipoprotein-cholesterol, triglyceride and lipoprotein (a) values were similar in these two groups. Results for HRT-E and HRT-EP subgroups were similar. 4. Carotid IMT was significantly reduced in the HRT group compared with men and non-HRT groups. Results for HRT-E and HRT-EP subgroups were similar. 5. Mean systemic arterial compliance (SAC) was significantly greater in men than in women and was related to age; SAC was higher in both HRT-E and HRT-EP groups compared with the non-HRT group. Indices of carotid stiffness were similar in men and in non-HRT groups. The HRT-EP group showed increased carotid stiffness compared with the HRT-E group. 6. There is an apparent protective effect of long-term oestrogen therapy on carotid IMT and age-related changes in arterial stiffness. Progestin does not alter the IMT effects but may adversely influence arterial stiffness.

Aged↗

Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women.

The possibility that the heightened cardiovascular risk associated with the menopause, which is said to be ameliorated by soybeans, can be reduced with soy isoflavones was tested in 21 women. Although several were perimenopausal, all have been included. A placebo-controlled crossover trial tested the effects of 80-mg daily isoflavones (45 mg genistein) over 5- to 10-week periods. Systemic arterial compliance (arterial elasticity), which declined with age in this group, improved 26% (P < .001) compared with placebo. Arterial pressure and plasma lipids were unaffected. The vasodilatory capacity of the microcirculation was measured in nine women; high acetylcholine-mediated dilation in the forearm vasculature was similar with active and placebo treatments. LDL oxidizability measured in vitro was unchanged. Thus, one important measure of arterial health, systemic arterial compliance, was significantly improved in perimenopausal and menopausal women taking soy isoflavones to about the same extent as is achieved with conventional hormone replacement therapy.

Adult↗

LDL particle size in subjects with previously unsuspected coronary heart disease: relationship with other cardiovascular risk markers.

Low density lipoprotein (LDL) particle diameters were determined by non-denaturing gradient gel electrophoresis in 53 subjects with previously unrecognised coronary heart disease (CHD) and 167 control subjects matched by age, sex and total plasma cholesterol. The mean diameter of the major LDL peak was found not to be significantly different between the two groups, but the CHD subjects were found to have a broader distribution of the predominant LDL species ((25.0 (24.7-25.3)nm versus 24.8 (24.7-24.9)nm)) (median (25-75%)), a greater proportion of larger particles (chi 2 = 19.8, P < 0.001) and to be more likely to have multiple numbers of LDL species than the control subjects (chi 2 = 22.7, P < 0.001). A negative correlation was found between the diameter of the predominant LDL species and fasting plasma triglyceride (r = -0.21, P = 0.0015), waist to hip ratio (WHR) (r = -0.15, P = 0.026) and body mass index (BMI) (r = -0.20, P = 0.002), and in a subgroup of subjects (n = 106), postprandial analysis revealed a negative correlation with the incremental postprandial response of plasma insulin (r = -0.19, P = 0.025). Male subjects had a significantly smaller diameter of the major LDL peak (24.8 +/- 0.0 nm) than female subjects (25.0 +/- 0.0 nm, P < 0.001). The present study failed to confirm an association between small LDL particles and the presence of coronary heart disease but did demonstrate more LDL heterogeneity in those with CHD. In addition, significant relationships were evident between the diameter of the major LDL peak and a number of other risk factors for coronary disease.

Anthropometry↗

Repair of experimental calvarial defects with Bio-Oss particles and collagen sponges in a rabbit model.

Various materials have been used for reconstruction of both acquired and congenital calvarial defects. Unfortunately, each has its limitations. Autologous bone grafts have irregular rates of resorption that may require secondary corrective surgery, and individual harvest sites have limited stores that can necessitate additional donor locations. Alloplastic materials have unlimited quantities and volume stability but they may not become incorporated and are associated with a higher incidence of infection. The optimal bone substitute should stimulate new bone formation and permanently supplant the temporary space filler, thereby reconstituting the surgical defect. We evaluated 2 newly available bone substitutes, resorbable natural bone mineral (Bio-Oss particles) and a combination of collagen and natural bone mineral collagen combination (Bio-Oss sponges), to repair calvarial defects in an adult, male, New Zealand white rabbit model. We found that the particulate Bio-Oss material resorbed and then underwent the normal physiological stages of bone remodeling. The collagen and Bio-Oss combination was replaced by new bone ingrowth. These materials may have potential for use in the reconstruction of skull defects.

Animals↗

Aortic distensibility and left ventricular structure and function in isolated systolic hypertension.

Aortic mechanical properties were assessed in a group of elderly subjects with untreated isolated systolic hypertension using two-dimensional echocardiography. Echocardiographic (two-dimensional and Doppler) assessment of left ventricular structure and function was also made. Ten subjects (mean age 71.7 +/- 1.9 years, 20% male, mean clinic blood pressure 163.6/79.2 +/- 1.2/2.0 mmHg) were compared with 16 normotensive subjects of similar age (69.4 +/- 1.6 years, 38% male, mean clinic blood pressure 129.8/78.2 +/- 3.2/2.9 mmHg). Aortic distensibility at the level of the transverse aortic arch was significantly reduced among subjects with isolated systolic hypertension. The thickness of the interventricular septum was approximately 20% greater in the hypertensive subjects (P < 0.01) and the average wall thickness to radius ratio was increased by 30%. Patterns of transmitral diastolic flow were also different in subjects with isolated systolic hypertension. Deceleration time was significantly greater (P < 0.01) and the ratio of early to late transmitral diastolic peak flow velocities was significantly less in the hypertensive (P < 0.05) than in the normotensive group. Left ventricular systolic function was well preserved. These findings are consistent with the suggestion that isolated systolic hypertension represents a state of increased aortic stiffness which may contribute to the development of left ventricular hypertrophy. Whether this increase in aortic stiffness is the cause or effect of the elevated systolic blood pressure remains unresolved.

Aged↗

The effects of insulin-like growth factor-1 on critical-size calvarial defects in Sprague-Dawley rats.

In a previous study prepared in 1992, we found that insulin-like growth factor-1 showed promise in hastening intramembranous bone repair in midfacial bone defects. For the present study, we created critical-size calvarial defects in 36 adult male Sprague-Dawley rats. The rats were then divided into two groups and killed at 1, 2, 3, 4, 5, 6, and 8 weeks. Twenty-one rats were administered insulin-like growth factor-1 subcutaneously with a 14-day osmotic infusion pump. An untreated group served as controls. Results were compared using routine histology to examine bone reconstitution of the surgical defects. Within the experimental group, we observed repair commenced at approximately 1 week and the critical-size calvarial bone defects were completely obliterated by 6 weeks; in the control group, even by 8 weeks, the surgical defects remained almost unchanged. In summary, this is further evidence that insulin-like growth factor-1 may have the potential to accelerate repair of intramembranous bone defects.

Animals↗

Reconstruction of calvarial defects with anorganic bovine bone mineral (Bio-Oss) in a rabbit model.

Reconstructive surgeons have employed various procedures using either autogenous or alloplastic materials to repair cranial defects secondary to trauma, extirpative surgery, or congenital anomalies. Currently, the choice appears to be dependent on the personal choice or background of the operating surgeon. For years, our preference has been to use calvarial bone grafts as our primary source of reconstructive material. Disadvantages include uneven resorption of the bone grafts and limited quantities. For these reasons, bony substitutes present new possibilities for reconstruction of craniomaxillofacial defects. We evaluated Bio-Oss, which is a natural bone mineral derived from a bovine source that is chemically and physically identical to human bone, as a possible replacement material to reconstruct skull defects in a rabbit model.

Animals↗

Polyglyconate plates and screws to stabilize zygomatic osteotomies in a rabbit model.

Rigid internal fixation with miniplates and screws continues to be widely used in the correction of both congenital and acquired craniomaxillofacial deformities. This technique allows precise three-dimensional stabilization of bony segments. A number of recent reports have detailed some disadvantages, including potential growth restriction in developing children, bone resorption, infection, extrusion, and palpability. These problems have often necessitated secondary surgery for hardware removal. A biodegradable plate and screw system would eliminate these potential and real problems. Over the last 2 decades, there has been an escalating interest in developing satisfactory biodegradable materials for bony fixation. We have previously reported the initial phases of a long-term evaluation of various biomaterials currently available. The purpose of this study is to examine a biodegradable plate and screw system fabricated from a faster resorbing material--polyglyconate. This system would be applicable to pediatric reconstructive problems. Earlier studies have shown its tissue compatibility and feasibility for multiple surgical uses. Osteotomies were created at the midpoint of each zygomatic arch of 42 adult male white New Zealand rabbits. The animals were then divided into two equal groups. The first group served as a control and the bony segments were permitted to heal without stabilization, whereas in the experimental group, the bony segments were stabilized with biodegradable plates and screws made from polyglyconate. Animals were then sacrificed at 2, 4, 6, 8, 12, and 16 weeks, at which time radiographs were obtained. Zygomatic complexes were then removed en bloc, and routine hematoxylin and eosin slides were made for light microscopy. Without fixation, fracture segments became significantly displaced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗