Abnormal uptake and washout of thallium-201 in patients with syndrome X and normal-appearing scans.
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Age Factors↗
Biomedical subjects
P Collins
Publications and source records attributed to P Collins.
Testosterone relaxes rabbit coronary arteries and aorta.
BACKGROUND: Until menopause, women appear to be protected from coronary heart disease. Evidence suggests that estrogen may play a role in the protection of the cardiovascular system by exerting a beneficial effect on risk factors such as cholesterol metabolism and by a direct effect on the coronary arteries. To date there has been no evidence linking testosterone with the occurrence of coronary heart disease. Testosterone may affect the cardiovascular system directly, thus partially explaining the difference in the incidence of coronary artery disease in men and premenopausal women. The purpose of this study was to assess the direct effect of testosterone and a number of testosterone analogues on rabbit coronary arteries and aorta in vitro. METHODS AND RESULTS: Rings of coronary artery and aorta of adult male or nonpregnant female New Zealand White rabbits were suspended in organ baths containing Krebs solution; isometric tension then was measured. The response to testosterone was investigated in prostaglandin F2 alpha (PGF 2 alpha)- and KCl-contracted rings. The effects of endothelium and nitric oxide synthase, prostaglandin synthetase, and guanylate cyclase inhibition on testosterone-induced relaxation were investigated. The effects of ATP-sensitive potassium channels and potassium conductance were also assessed. Relaxing responses in the presence of aromatase inhibition and testosterone receptor blockade were performed. The relaxing responses to the testosterone analogues etiocholan-3 beta-ol-17-one, epiandrosterone, 17 beta-hydroxy-5 alpha-androst-1-en-3-one, androst-16-en-3-ol, and testosterone enanthanate were measured. Testosterone relaxed rabbit coronary arteries and aorta. There was no significant difference between the relaxation effect of testosterone with or without endothelium. Similar results were obtained from male and nonpregnant female rabbits. The relaxing response of testosterone in the coronary artery was significantly greater than in the aorta. The relaxing response of testosterone in the coronary artery was significantly reduced by the potassium channel inhibitor barium chloride but not by the ATP-sensitive potassium channel inhibitor glibenclamide. The relaxing response to testosterone was greater in PGF 2 alpha-contracted rings compared with KCl-contracted rings. Inhibitors of nitric oxide synthase, prostaglandin synthetase, and guanylate cyclase did not affect relaxation induced by testosterone. Inhibition of aromatase and testosterone receptors did not affect relaxation. Testosterone did not shift the rabbit coronary arterial calcium concentration-dependent contraction curves, whereas verapamil did. There were, however, significant differences in the relaxing response to testosterone compared with testosterone analogues. Testosterone was the most potent relaxing agent, suggesting that there may be a structure-function relation in the relaxing response. CONCLUSIONS: Testosterone induces endothelium-independent relaxation in isolated rabbit coronary artery and aorta, which is neither mediated by prostaglandin I2 or cyclic GMP. Potassium conductance and potassium channels but not ATP-sensitive potassium channels may be involved partially in the mechanism of testosterone-induced relaxation. The in vitro relaxation is independent of sex and of a classic receptor. The coronary artery is significantly more sensitive to relaxation by testosterone than the aorta. Testosterone is a more potent relaxing agent of rabbit coronary artery than other testosterone analogues.
Animals↗
The effect of reduction of lipoprotein (a) on cellular cholesterol synthesis in non-diabetic and type 2 diabetic subjects.
This study investigates the effect of Lipoprotein (a) (Lp(a)) on cellular cholesterol synthesis in non-diabetic (n = 7) and Type 2 (non-insulin-dependent) diabetic subjects (n = 7) with elevated levels of Lp(a) (> 20 mg/dl). N-Acetylcysteine was used to lower Lp(a) in the control subjects and their lipoproteins were re-examined after 7 days of treatment. Low-density lipoprotein (LDL) was isolated and separated from Lp(a) by sequential ultracentrifugation. Regulation of cellular cholesterol synthesis was assessed by measuring incorporation of [14C]acetate into mononuclear leucocytes in the presence of LDL and Lp(a). Cellular cholesterol content was determined by a fluorometric assay. Delivery of cholesterol to the cell was examined using [3H]cholesteryl oleate-labelled LDL or Lp(a). LDL (5 micrograms/ml) from non-diabetic subjects suppressed cellular cholesterol synthesis by 66.2%, while Lp(a) at a similar concentration only suppressed cholesterol synthesis by 5.8% (P < 0.001). At a concentration of 20 micrograms/ml, Lp(a) suppressed cholesterol synthesis by 31.7%. The situation was similar in the diabetic subjects. Serum LDL cholesterol in non-diabetic subjects was 4.2 +/- 0.5 mmol/l and the LDL esterified/free cholesterol ratio was 2.6 +/- 0.2. Following treatment with N-acetylcysteine, LDL cholesterol did not change, while Lp(a) decreased significantly by 24% (P < 0.05). The LDL esterified/free cholesterol ratio decreased to 2.2 +/- 0.2 (P < 0.05) and there was a significant increase in the ability of the subjects LDL to inhibit cellular cholesterol synthesis (P < 0.05). There was a significant negative correlation between plasma Lp(a) and the ability of the patients' LDL to inhibit cellular cholesterol synthesis (r = -0.68, P < 0.01). [3H]Cholesteryl-oleate-LDL (5 micrograms/ml) delivered 266 +/- 13 ng cholesteryl oleate/mg cell protein, while it took 20 micrograms of [3H]cholesteryl oleate-labelled-Lp(a) to deliver a similar concentration (315 +/- 21 ng cholesteryl oleate/mg cell protein). In conclusion it appears possible that the atherogenicity of Lp(a) may be associated with its effect on the LDL receptor which alters LDL receptor uptake, LDL composition and cellular cholesterol synthesis.
Acetylcysteine↗
Abdominal aortic aneurysm in the Irish population: a familial screening study.
A pilot screening programme was undertaken in Ireland to determine the incidence of abdominal aortic aneurysm (AAA) (diameter 3 cm or greater) in the siblings of 120 patients known to have AAA. There were 621 siblings; 270 of them were dead, 32 were over 80 years old and 85 lived outside Ireland, leaving 234 under 80 years of age still living in Ireland who were invited to attend for ultrasonographic screening. Of the 270 siblings who had died, 102 were women and 168 men; eight men (4.8 per cent) had died from ruptured AAA. Only 125 (53.4 percent) of the 234 siblings agreed to participate in the screening programme, 60 brothers from 31 families and 65 sisters from 35 families. Fifteen (12.0 per cent) of the 125 siblings had an AAA (median size 4.2 (range 3.1-6.8) cm), 13 (22 per cent) of the 60 male siblings and two (3 per cent) of the 65 female siblings. The prevalence of AAA among siblings was not affected by the age or sex of the patient with aneurysm. Seven of the 14 male siblings with hypertension had an AAA, compared with only six of the 46 who were normotensive (P = 0.01). The high incidence of AAA in brothers of affected patients highlights the need to counsel this group on their risk of aneurysm. The relatively low participation rate by siblings in this screening programme indicates that a hospital-based unit is unlikely to be effective in recruiting all patient siblings at risk from an AAA.
Adult↗
The terminology of early development: history, concepts, and current usage.
The meaning of some terms used in describing the development of embryos is discussed in the light of their historical origin and current usage. Attention is focused on the terminology associated with the early development of animals, particularly that concerned with gastrulation and germ layer theory. It is suggested that terms linked with outdated concepts are not always appropriate for, and unless defined with care may limit, our appreciation of the significance of subsequent observation and experiment. Recommendations are made concerning the use of the terms mesoblast, mesoderm, and mesenchyme.
Animals↗
Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition.
The increased risk of atherosclerotic disease in diabetic subjects may be due to enhanced foam cell formation following an increased susceptibility of low density lipoprotein to oxidative modification. This study has compared fatty acid content and lipoprotein oxidisability in 10 non-insulin-dependent diabetic subjects with that in 10 control subjects. Both groups were normocholesterolaemic and the diabetic subjects had higher triglyceride levels (2.2 +/- 0.4 vs 1.2 +/- 0.2 mmol/l, p < 0.05). The fatty acid composition was compared in low density lipoprotein following Folch extraction, separation by thin layer chromatography (for the lipid classes) and analysis by gas liquid chromatography. Low density lipoprotein oxidisability was assessed by conjugated diene and thiobarbituric acid reacting substance formation in the presence of copper ions. The esterified/free cholesterol ratio was higher in the low density lipoprotein from patients compared to control subjects (2.9 +/- 0.1 vs 1.9 +/- 0.3, p < 0.05). Linoleic acid in the cholesteryl ester fraction of the lipoprotein was higher in the patients than in the control subjects (48.2 +/- 2.2% vs 42.4 +/- 3.4%, p < 0.05) as was the total quantity of linoleic acid in the cholesteryl ester fraction (317.8 +/- 68.0 vs 213.2 +/- 28.0 micrograms/mg protein, p < 0.05) and in the low-density lipoprotein as a whole (443.2 +/- 70.0 vs 340.2 +/- 28.2 micrograms/mg protein, p < 0.05). Lipoprotein oxidisability was also increased in the diabetic group with increased formation of thiobarbituric acid reacting substances (35.6 +/- 7.2 vs 22.3 +/- 3.5 nmol/mg protein, p < 0.05, increased total diene formation (502 +/- 60 vs 400 +/- 30 nmol/mg protein, p < 0.05) and increased rate of diene formation (7.2 +/- 0.6 vs 5.1 +/- 0.9 nmol diene.mg protein-1.min-1, p < 0.05). This study indicates that low-density lipoprotein from diabetic subjects is more susceptible to oxidation. This could, in vivo, accelerate foam-cell formation thereby increasing atherosclerotic risk in diabetic subjects.
Aged↗
Intestinally derived lipoprotein particles in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia.
We have previously demonstrated alterations in apolipoprotein B-48 metabolism in the post-prandial state in patients with non-insulin-dependent diabetes mellitus. This study investigates the relationship between hypertriglyceridaemia and post-prandial lipoprotein metabolism. Four groups of patients were examined: non-insulin-dependent diabetic patients, with normal serum triglyceride levels (serum triglyceride < 2.1 mmol l-1; haemoglobin HbA1c 5.5% +/- 0.4%); poorly controlled, non-insulin-dependent diabetic patients with hypertriglyceridaemia (serum triglyceride > 2.1 mmol l-1; HbA1c 8.8% +/- 0.9%); non-diabetic subjects with serum triglycerides < 2.1 mmol l-1; and non-diabetic subjects with hypertriglyceridaemia (serum triglyceride > 2.1 mmol l-1). Subjects were studied fasting and following a high-fat meal (1300 kcal). The triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d < 1.006 g ml-1). Apoprotein B-48, apoprotein B-100 and apoprotein E were separated on 4%-15% gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Triglyceride-rich lipoprotein apolipoprotein B-48 and apolipoprotein B-100 post-prandial profiles demonstrated a maximum increase either at 2 h or rising still further to a peak at 6 h before falling in the diabetic groups and hypertriglyceridaemic non-diabetic subjects when compared with the normotriglyceridaemic control subjects whose levels decreased after 2 h (P < 0.05). A significantly different triglyceride-rich lipoprotein apolipoprotein E profile was also exhibited by the diabetic patients (P < 0.05). Levels of triglyceride-rich lipoprotein, cholesterol, triglyceride, total protein and apoprotein B were elevated in the hypertriglyceridaemic subjects, both diabetic and non-diabetic. These results indicate that hypertriglyceridaemia is associated with altered metabolism and composition of post-prandial triglyceride-rich lipoprotein particles in both poorly controlled diabetic and non-diabetic subjects.
Alleles↗
A structural feature of N-[2-(cyclohexyloxy)-4-nitrophenyl] methanesulfonamide (NS-398) that governs its selectivity and affinity for cyclooxygenase 2 (COX2).
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Animals↗
Mechanisms of estrogen-induced vasodilation: in vivo studies in canine coronary conductance and resistance arteries.
OBJECTIVES: We sought to examine the immediate vasodilator effect of intracoronary estrogen on epicardial and resistance coronary arteries in 19 dogs. BACKGROUND: Although estrogen reportedly dilates coronary arteries in vitro, the site and mechanisms of its action have not been fully defined in vivo. METHODS: Epicardial coronary artery dimensions and coronary flow velocity were assessed using simultaneous intracoronary two-dimensional and Doppler ultrasound. RESULTS: Estrogen (0.1 and 1 mumol/liter) induced a significant increase in coronary cross-sectional area, flow velocity and volumetric blood flow. Estrogen-induced vasodilation was not influenced either by pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME) (100 mumol/liter intracoronary), indomethacin (5 mg/kg body weight intravenously), propranolol (0.75 mg/kg intravenously) or the classic estrogen receptor antagonist ICI 182,780 (10 mumol/liter). Balloon denudation of the endothelium did not attenuate estrogen-induced epicardial vasodilation. Pretreatment with glibenclamide (10 mumol/liter) attenuated estrogen-induced vasodilation only in epicardial arteries, as did verapamil (0.1 mumol/liter). Estrogen had no effect on a phenylephrine dose-response curve in either epicardial coronary arteries or the microcirculation. CONCLUSIONS: Acute estrogen-induced dilation in canine coronary arteries is endothelium independent and is not mediated by the classic intracellular estrogen receptor but through non-genomic mechanisms, presumably at the membrane level, which in epicardial arteries may include effects on adenosine triphosphate-sensitive potassium or calcium channels, or both.
Analysis of Variance↗
Estrogen acutely increases peripheral blood flow in postmenopausal women.
PURPOSE: To test the acute effect of estrogen on peripheral blood flow and vascular resistance in postmenopausal women. PATIENTS AND METHODS: Eleven normotensive, post-menopausal female volunteers (mean age 53 +/- 6 years) were studied. Six women were in natural menopause and 5 had had a hysterectomy (mean age of the menopause 49 +/- 3 years). We used a double-blind, randomized protocol to assess the acute response to sublingual estradiol-17 beta (1 mg) on the forearm resistance vessels, compared with sublingual placebo. Blood flow was measured by strain-gauge plethysmography, and mean peripheral vascular resistance was then calculated. Mean blood pressure was also measured. RESULTS: The mean blood flow induced by estradiol-17 beta after 40 minutes was significantly greater than that induced by placebo (3.9 +/- 0.5 mL/100 mL per minute versus 2.4 +/- 0.4 mL/100 mL per minute, respectively, P < 0.05). The forearm resistance was significantly reduced at 40 minutes after estradiol-17 beta compared with placebo (25.7 +/- 4.4 resistance units (RU) to 44.4 +/- 6.4 RU, respectively, P < 0.05). Mean blood pressure 40 minutes after the administration of estradiol-17 beta was no different when compared with placebo (91 +/- 1.5 mm Hg versus 90 +/- 2.5 mm Hg, respectively, P = NS). CONCLUSIONS: These results indicate that the acute administration of estradiol-17 beta affects blood flow in the peripheral vasculature in human subjects. The mechanism of this effect has not been determined, but it may explain some of the beneficial effects of estrogen on the vascular system and have future therapeutic potential in postmenopausal women.
Administration, Sublingual↗
The effects of cardiopulmonary bypass on systemic and coronary levels of von Willebrand factor.
Von Willebrand factor antigen (vWF Ag) is a marker of endothelial injury which has been shown to rise during surgical procedures, including cardiopulmonary bypass (CPB). The aim of this study was to determine whether intermittent aortic cross-clamping during CPB causes the release of vWF Ag from the coronary vascular bed, which would suggest coronary vascular endothelial cell perturbation. Fifteen consecutive patients undergoing CPB with aortic cross-clamping during coronary artery bypass surgery and/or valve replacement by the same surgeon were studied. Paired venous and coronary sinus samples were taken pre- and post-thoracotomy, prior to cross-clamping on CPB, and 1, 5 and 10 minutes after release of the aortic cross-clamp. Plasma vWF Ag (IU/ml) was measured by ELISA. Venous vWF Ag measured prior to skin incision was 0.75 +/- 0.11 IU/ml (mean +/- SEM) and fell to 0.53 +/- 0.07 IU/ml after institution of CPB but prior to aortic cross-clamping (P < 0.01 vs pre-incision sample). Coronary sinus vWF Ag measured prior to aortic cross-clamping was 0.54 +/- 0.06 IU/ml (P = NS vs paired venous sample). At 1, 5 and 10 min after release of the aortic cross-clamp there was a progressive rise in vWF Ag in both venous and coronary sinus samples (1 min: 0.67 +/- 0.05 IU/ml vs 0.75 +/- 0.10 IU/ml, 5 min: 0.73 +/- 0.07 IU/ml vs 0.76 +/- 0.09 IU/ml, 10 min: 0.74 +/- 0.08 IU/ml vs 0.79 +/- 0.09 IU/ml; P = NS venous vs coronary sinus, respectively). Levels of vWF Ag were highest immediately prior to the termination of CPB (venous: 0.95 +/- 0.12 IU/ml; coronary sinus: 0.91 +/- 0.14 IU/ml). We conclude that cardiac surgery using CPB with aortic cross-clamping is associated with a progressive rise in coronary sinus and venous levels of vWF Ag.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Coronary intravascular ultrasound--is it coming of age?
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Coronary Disease↗
Syndrome X in women is associated with oestrogen deficiency.
This study was undertaken to ascertain whether gynaecological history or a reduction in ovarian hormones are triggers of angina in menopausal women with a positive exercise test and normal coronary arteries. The majority of patients with angina pectoris, a positive exercise test and normal coronary arteries are female, suggesting that the female gender may be important in the aetiology. We studied the gynaecological features of 107 women (age 53 +/- 9 years) with syndrome X, taken from a population of 134 patients including 27 males. Cardiological investigations were undertaken and detailed gynaecological history obtained from all the female patients. Menopausal status was confirmed by plasma levels of oestradiol-17 beta < or = 100 pmol.l-1. In 95 of the 107 female patients, chest pain began either during the perimenopausal period (32) or after the menopause (63). Of the 63 menopausal patients, 43 had undergone hysterectomy at an average of 8 +/- 6 years prior to the onset of chest pain. The incidence of hysterectomy in the study population (40%) was four times greater than that of an age-matched population. These findings confirm that the majority of patients with syndrome X are women in whom the chest pain began after the onset of menopause. Ovarian hormone deficiency may, therefore, play a role in the onset of syndrome X in female patients.
Adult↗
Oestrogen relaxes human epicardial coronary arteries through non-endothelium-dependent mechanisms.
BACKGROUND: Oestrogen-replacement therapy is associated with a reduced incidence of cardiovascular disease. The acute administration of oestrogen improves myocardial ischemia in women with coronary heart disease. In this study we investigated the relaxing effect of oestradiol-17 beta on human coronary arteries in vitro and determined the role of endothelial modulation in this relaxation by using isolated human coronary arteries. METHODS: Atherosclerosis-free epicardial arteries from men and women were removed from patients undergoing heart or combined heart and lung transplantation. The arteries were cut into ring segments and placed into organ baths containing Tyrode's solution. Changes in isometric tension were measured. The relaxing response to oestradiol-17 beta (10(-10) - 10(-5) mol/l) was investigated and the effects of endothelium, NGmonomethyl-L-arginine and indomethacin on the response of oestradiol-17 beta were assessed. RESULTS: Oestradiol-17 beta (10(-10) - 10(-5) mol/l) induced significant relaxation in coronary arteries pre-contracted with the thromboxane A2 analog (U46619; 3 x 10(-8) mol/l). Relaxation was significantly greater in coronary arteries from female patients. No significant differences were observed between arteries with or without endothelium nor after nitric oxide synthase or cyclo-oxygenase inhibition. These results indicate that oestradiol-17 beta induces human coronary artery relaxation via an endothelium-independent mechanism in vitro. The sex of the patients significantly affects sensitivity of the coronary arterial rings to oestrogen. CONCLUSION: Oestradiol-17 beta-induced coronary relaxation may play an important role in regulation of coronary tone, and may partly explain why oestrogen improves myocardial ischemia in women and why it protects postmenopausal women from the risk of developing coronary heart disease.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Construction of a herpes simplex virus/varicella-zoster virus (HSV/VZV) thymidine kinase recombinant with the pathogenic potential of HSV and a drug sensitivity profile resembling that of VZV.
A recombinant of herpes simplex virus (HSV) was constructed in which the HSV thymidine kinase (TK) gene was deleted and the varicella-zoster virus (VZV) TK gene was introduced into the US5 region under the control of the human cytomegalovirus IE promoter. Infection with the recombinant (R18) led to the induction of TK although the kinetics of synthesis resembled those of a 'late' gene product. The recombinant was virulent in the zosteriform mouse model with the pattern of pathogenesis similar to that of wild-type HSV-1. The sensitivity of the recombinant to several nucleoside analogues was assessed and in most cases (BVaraU, ACV and GCV) it resembled VZV rather than HSV. The enhanced sensitivity of the recombinant to BVaraU compared with wild-type HSV resulted in a far greater response to treatment with BVaraU as assessed in the mouse model.
Acyclovir↗
Narrowband (TL-01) UVB air-conditioned phototherapy for atopic eczema in children.
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Adolescent↗
Narrow-band UVB (TL-01) phototherapy: an effective preventative treatment for the photodermatoses.
Twenty patients with photodermatoses [actinic prurigo (n = 6), hydroa vacciniforme (n = 4), idiopathic solar urticaria (n = 1), amiodarone-induced photosensitivity (n = 1) and a range of cutaneous porphyrias (n = 8)] were treated with a 'hardening' course of narrow-band ultraviolet B (TL-01) phototherapy in springtime. The response to phototherapy was monitored subjectively, by interviewing patients after the summer, and objectively by monochromator phototesting, before and after phototherapy. Fifteen patients reported that treatment was worthwhile. Monochromator phototesting after phototherapy revealed a fourfold increase in the minimal erythema dose in those with abnormal photosensitivity to ultraviolet A wavebands. Adverse effects included erythema (seven patients), pruritus (five) and provocation of the eruption (four). We now routinely consider narrow-band UVB phototherapy for problem photodermatoses.
Adolescent↗