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Biomedical subjects

G A Ferns

Publications and source records attributed to G A Ferns.

At least 19 recordsLinked to original sources
PubMed2001

Minor myocardial injury after elective uncomplicated successful PTCA with or without stenting: detection by cardiac troponins.

Cardiac troponins are sensitive and specific markers for the detection of minor myocardial injury. However, they have been rarely used to monitor myocardial injury after coronary stenting. The purpose of the study was to measure cardiac troponin I (cTnI) and cardiac troponin T (cTnT) levels after elective uncomplicated successful percutaneous transluminal coronary angioplasty (PTCA) with or without coronary stenting and to compare their results with serum creatinine kinase MB isoenzyme (CKMB). CTnI and cTnT levels were compared with those of CK or CKMB in 98 consecutive patients with stable angina undergoing elective uncomplicated successful PTCA with stenting (n = 71) or without stenting (n = 27). Markers were measured before and 6, 12, 24, and 48 hr after the procedure. Peak postprocedural levels for each marker were compared and related to angiographic and procedural characteristics as well as to the occurrence of side-branch occlusion. None of the patients had abnormal markers before the procedure. Abnormal postprocedural values of one or more markers were observed in 28 patients (29%), 23 after stenting and 5 after PTCA alone. The frequencies of abnormal cTnI and cTnT levels were significantly higher than that of CKMB after coronary intervention (26% and 18% vs. 7%; P = 0.00016 and 0.015, respectively), with cTnI being the most significant. When compared with troponin-negative patients, abnormal cardiac troponin values were significantly related to total time of inflation (223 +/- 128 vs. 170 +/- 105 sec; P = 0.008) and inflation maximal pressure (12.9 +/- 2.3 vs. 12.0 +/- 2.7 atm; P = 0.04). Small side-branch occlusion was noticed in 36% of the troponin-positive patients and in 6% of the troponin-negative group (P = 0.00047). In conclusion, minor myocardial injury is not uncommon after elective uncomplicated successful PTCA with or without stenting. Cardiac troponins, especially cTnI, are more sensitive than CKMB for the detection of this minor myocardial injury. Total time of inflation and inflation maximal pressure are predictors of postprocedural elevation of cardiac troponins. Side-branch occlusion may account for some, but not all, periprocedural minor myocardial injury.

Adult↗
PubMed2001

Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit.

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. We have investigated the effects of graded dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Rabbits (n = 40) were fed a 0.25-1% cholesterol diet deficient in copper. Animals received either 0, 1, 3 or 20 mg copper/day and were killed after 13 weeks. Plasma cholesterol levels were similar in each dietary group. Aortic concentrations of copper were higher in the 20 mg copper/day animals compared to those receiving 0 mg copper/day (3.70 +/- 0.78 vs. 1.33 +/- 0.46 microg/g wet tissue; P < 0.05). Aortic superoxide dismutase activity was higher in animals receiving 20 mg copper/day (323 +/- 21 IU/mg tissue) compared to the other groups (187 +/- 21; 239 +/- 53; 201 +/- 33 IU/mg tissue) (P > 0.05). En face staining of aortae with oil red O showed that both high copper supplementation (20 mg/day) (67.1 +/- 5.5%) and a deficient diet (0 mg/day) (63.1 +/- 4.8%) was associated with significantly larger lesions (P < 0.05) compared to moderately supplemented animals (1 mg/day and 3 mg/day) (51.3 +/- 6.3 and 42.8 +/- 7.9%). These data indicate that in the cholesterol-fed rabbit, there is an optimal dietary copper intake and that dietary copper deficiency or excess are associated with an increased susceptibility to aortic atherosclerosis. Many Western diets contain insufficient copper and these findings indicate that a moderate dietary copper content may confer a degree of cardiac protection to the human population.

Animals↗
PubMed2001

Changes in serum concentration of antioxidants following treadmill exercise testing in patients with suspected ischaemic heart disease.

Twenty-four subjects with suspected ischaemic heart disease underwent a treadmill exercise stress test (TEST). Nine individuals developed ischaemia as defined by standard criteria. Total plasma antioxidant status (TPAS), and serum concentrations of vitamin E were measured pre-TEST, and 0, 1, 2, 4, 8 and 24 h following the treadmill test. Mean serum vitamin E concentrations fell by 33% in the group as a whole (from 9.53 +/- 0.92 mg/L pre-TEST to 6.39 +/- 1.06 mg/L immediately post stress test, P < 0.02) and rose to baseline over the subsequent 24 h. The levels of serum vitamin E fell by 34% in the group of patients who had a positive TEST, and 32% in those who did not develop ischaemia during the TEST. Serum cholesterol concentrations also fell significantly during the TEST. In the total group serum cholesterol fell by 6.5% (P = 0.0052), and in the subgroup who were positive for ischaemia the fall in serum cholesterol was 10.3% (P = 0.004). The reduction in serum cholesterol was 4.1% in the subgroup who did not develop ischaemia (P > 0.05). Mean total plasma antioxidant status showed no significant temporal change for the group as a whole, although there was a nonsignificant decrease immediately post-TEST in the ischaemic group and a slight rise at 8 h in the group negative for ischaemia.

Adult↗
PubMed2001

Endogenous neutralizing antibodies against platelet-derived growth factor-aa inhibit atherogenesis in the cholesterol-fed rabbit.

Previous studies have shown that the B chain of platelet-derived growth factor (PDGF) has an important role in atherogenesis. In this study we have investigated the contribution of PDGF-A chain in cholesterol-induced atherogenesis in the New Zealand White rabbit. High titers of antibodies to PDGF-AA or to platelet cytosolic protein (PCP) were induced in these animals by immunization against recombinant human PDGF-AA or human PCP. Rabbits were then fed a 0.25% to 1% cholesterol-containing diet for 10 weeks to induce atherosclerotic lesions; the rabbits were then humanely killed and perfusion-fixed and their aortas were removed. The extent of atherosclerosis in the thoracic aortas was determined by quantitative morphometry after staining with oil red O. The intimal and medial areas in histological sections taken at the level of the first intercostal branch were quantified by image analysis. Immunization against PDGF-AA and PCP, but not against adjuvant alone, resulted in rising titers of antibodies within 2 weeks, the levels of which reached a plateau by 8 weeks. The antibodies to PDGF-AA were isoform-specific, recognized both human and rabbit PDGF-AA, and neutralized the biological activity of PDGF-AA in vitro. Integrated plasma cholesterol levels were similar in both groups. Compared with nonimmune rabbits (n=10), animals immunized against PDGF-AA (n=10) or PCP (n=10) had significantly smaller areas of the aorta covered by atherosclerotic lesions (24.6+/-5.1% and 18.7+/-4.2%, respectively, vs 34.4+/-4.3%; P<0.05). This was associated with a reduced aortic intimal-medial area ratio in PDGF-AA-immunized (0.009+/-0.006) and PCP-immunized (0.025+/-0.017) rabbits than in nonimmune animals (0.159+/-0.066; P<0.05). These data suggest that PDGF-AA is actively involved in cholesterol-induced atherosclerosis in the rabbit.

Animals↗
PubMed2000

Mononuclear cell adhesion to collagen ex vivo is related to pulse pressure in elderly subjects.

Mononuclear cells and platelets are intimately involved in the pathogenesis and complications of cardiovascular disease. Platelet activation has been reported in hypertension, though the activation-state of monocytes has received less attention. In this study the adhesiveness of monocytes and platelets was assessed and any relationship between the adhesive properties of these cellular elements and plasma levels of soluble adhesion molecules and blood pressure parameters determined. Fifty six elderly volunteers, of whom 32 were classified hypertensive (daytime SBP > or = 135 mmHg), underwent 24 h blood pressure monitoring, assessment of monocyte and platelet adhesion and measurement of the plasma soluble adhesion molecules ICAM-1, L-selectin, E-selectin and vWF. In the elderly hypertensive subjects, monocyte adhesion to collagen coated (P < 0.05) and tissue culture plastic microwells (P < 0.05) was significantly elevated and circulating levels of soluble ICAM-1 (P < 0.01) and soluble E-selectin (P < 0.05) were significantly raised compared to their normotensive counterparts. A significant correlation was found to exist between monocyte adhesion to collagen and daytime pulse pressure (r = 0.39, P < 0.01) and also between plasma levels of soluble E-selectin and clinic DBP (r = 0.40, P < 0.001). The increased monocyte adhesion witnessed in hypertensive subjects and with increasing pulse pressure may contribute to the increased risk of cardiovascular disease in hypertension. Whether this increased adhesiveness is a property of the monocytes. or reflects endothelial cell activation, remains to be determined.

Aged↗
PubMed2000

The mechanisms of coronary restenosis: insights from experimental models.

Since its introduction into clinical practice, more than 20 years ago, percutaneous transluminal coronary angioplasty (PTCA) has proven to be an effective, minimally invasive alternative to coronary artery bypass grafting (CABG). During this time there have been great improvements in the design of balloon catheters, operative procedures and adjuvant drug therapy, and this has resulted in low rates of primary failure and short-term complications. However, the potential benefits of angioplasty are diminished by the high rate of recurrent disease. Up to 40% of patients undergoing angioplasty develop clinically significant restenosis within a year of the procedure. Although the deployment of endovascular stents at the time of angioplasty improves the short-term outcome, 'in-stent' stenosis remains an enduring problem. In order to gain an insight into the mechanisms of restenosis, several experimental models of angioplasty have been developed. These have been used together with the tools provided by recent advances in molecular biology and catheter design to investigate restenosis in detail. It is now possible to deliver highly specific molecular antagonists, such as antisense gene sequences, to the site of injury. The knowledge provided by these studies may ultimately lead to novel forms of intervention. The present review is a synopsis of our current understanding of the pathological mechanisms of restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2000

Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons.

OBJECTIVES: To determine the effect of oral vitamin C supplements on ambulatory blood pressure and plasma lipids. DESIGN: A 6-month double-blind randomized placebo-controlled cross-over study with a 1 -week washout between cross-over periods. METHODS: Vitamin C 500 mg daily or matching placebo was given to 40 men and women aged between 60 and 80 years for 3 months each in a cross-over fashion. Clinic and 24-h ambulatory blood pressure, plasma ascorbate and lipids were measured at baseline and at the end of each cross-over phase. RESULTS: Clinic blood pressure did not change between placebo and vitamin C phases. Daytime ambulatory blood pressure showed a small but significant fall in systolic blood pressure (2.0 +/- 5.2 mmHg; 95% confidence interval 0-3.9 mmHg) but not in diastolic blood pressure. Regression analysis showed that with increasing baseline daytime blood pressure the fall in blood pressure with vitamin C supplementation increased. Regression analysis of the change in high-density lipoprotein (HDL) cholesterol showed a significant effect of sex on the change in HDL cholesterol. In women, but not men, HDL cholesterol increased significantly by 0.08 +/- 0.11 mmol/l, P=0.007. There was no change in low-density lipoprotein cholesterol between treatment periods. CONCLUSION: In older adults high intakes of ascorbic acid have modest effects on lowering high systolic blood pressure, which could contribute to the reported association between higher vitamin C intake and lower risk of cardiovascular disease and stroke.

Aged↗
PubMed2000

Antioxidant vitamin concentrations and LDL oxidation in nephrotic syndrome.

The increased risk of atherosclerosis in nephrotic syndrome is attributable in part to the associated hyperlipidaemia. The importance of oxidation of LDL in the atherogenic process has been recognized over the last 15 years. However, there are few data on the balance of antioxidant defences and lipoprotein oxidation in nephrotic syndrome. Plasma antioxidant vitamin concentrations and indices of LDL oxidation (LDL lipid hydroperoxide content and the susceptibility of LDL to oxidation) were measured in two groups of patients; group I comprised 29 nephrotic patients and group II comprised 25 patients with haematuria. Plasma ascorbate concentration was significantly lower in group I (the nephrotic group) compared with group II (median 13.3 versus 22.2 micromol/L; P<0.001). Vitamin E concentrations were higher in group I but were not significantly different if corrected for total plasma cholesterol (6.12 versus 5.88 micromol/mmol; P=0.33). However, these changes resulted in a low ascorbate:vitamin E ratio in group I (0.19 versus 0.87; P<0.0001). Despite these changes in important antioxidant vitamin concentrations, we were unable to demonstrate any increased susceptibility to LDL oxidation in vitro or any difference in LDL lipid hydroperoxide content. These data suggest that there may be a relative defect of oxidant/antioxidant balance in nephrotic syndrome which could predispose to increased oxidative stress. However, measures of LDL oxidation were not significantly different between the two groups. LDL was protected from oxidation despite the severe hyperlipidaemia and the low circulating vitamin C concentrations.

Adult↗
PubMed2000

Effect of vitamin E supplementation on circulating cell adhesion molecules pre- and post-coronary angioplasty.

The soluble adhesion molecules P-selectin (sP-selectin) and intercellular adhesion molecule-1 (sICAM-1) are derived from platelets and endothelial cells. Circulating concentrations of these soluble adhesion molecules are raised in patients with atherosclerosis and following percutaneous transluminal coronary angioplasty (PTCA). We have investigated the effects of vitamin E supplements (800 IU/day) on circulating plasma ICAM-1 and P-selectin levels pre- and post-PTCA. Patients, randomized to group, were pre-treated with vitamin E or placebo (soybean oil) for 1 month before routine PTCA. Plasma sICAM-1 and sP-selectin were measured by enzyme-linked immunosorbent assay on blood taken immediately pre- and post-PTCA. Total protein and alpha-tocopherol were measured on the same samples. Plasma alpha-tocopherol concentrations increased in patients receiving vitamin E: 19.1 (1.5) [mean (standard error of the mean, SEM)] mg/mL post-PTCA versus 13.9 (0.6) mg/mL pre-PTCA (n=23; P<0.01). Plasma sP-selectin and sICAM-1 levels were not significantly increased following PTCA in the vitamin E group. Pre-angioplasty mean (SEM) plasma sP-selectin concentration in the vitamin E group was 8.83 (0.97) ng/mg protein; the corresponding mean post-angioplasty value was 9.34 (0.89) ng/mg protein (P=0.85). The mean (SEM) pre-angioplasty sICAM-1 concentration in this group was 2.18 (0.24) ng/mg protein, and was 2.20 (0.23) ng/mg protein following angioplasty (P = 0.84). In the placebo group (n = 24) there was a significant increase in mean (SEM) sP-selectin concentration following angioplasty, from 7.48 (0.73) to 9.70 (0.78) ng/mg protein (P<0.05). The change (mean, SEM) in plasma sP-selectin concentration following angioplasty was significantly greater for the placebo group [2.22 (0.50) ng/mg protein] than for the group receiving vitamin E [0.50 (0.50) ng/mg protein] (P<0.02). This difference remained significant (P<0.05) even after adjustment for pre-angioplasty P-selectin concentrations. Mean (SEM) plasma sICAM-1 concentrations remained unchanged following angioplasty [pre-angioplasty: 2.16 (0.20) ng/mg protein; post-angioplasty: 1.97 (0.13) ng/mg protein]. Vitamin E may therefore limit platelet or endothelial activation during PTCA.

Adult↗
PubMed2000

Cardiac markers for assessing the acute coronary syndromes. A focus on cardiac troponins.

Markers of myocardial injury will continue to play an essential role in the assessment and management of patients presenting within the spectrum of acute coronary syndromes, a term representing the continuum of acute myocardial ischemia ranging from angina through Q-wave myocardial infarction. Coronary artery lesion instability can be detected by markers of plaque inflammation and disruption, platelets reactivity, and thrombosis. When myocardial injury occurs with severe impairment of coronary blood flow, several markers are released from the damaged myocyte. For many years, creatine kinase-MB isoenzyme has been the conventional marker for myocardial infarction. Despite its inadequate sensitivity and specificity for myocardial injury, creatine kinase-MB remains an essential component in assessing re-infarction or infarct extension, as well as in monitoring reperfusion after thrombolytic therapy when combined with myoglobin. Among the many cardiac markers for myocardial necrosis, cardiac troponins possess superior sensitivity and specificity for the detection of myocardial injury. In addition to their superior performance in detecting minor myocardial damage, cardiac troponins can be useful in detecting perioperative myocardial infarction, infarct size, improving risk stratification, and facilitating therapeutic decision making in patients with acute coronary syndromes.

Acute Disease↗
PubMed1999

Infection, immunisation and atherosclerosis: is there a link?

Atherosclerosis is the predominant underlying pathology responsible for coronary heart disease (CHD). It bears all the hallmarks of a chronic inflammatory disease and typical atherosclerotic lesions contain activated macrophages and T-cells. There have been several reports of possible associations between prior exposure to a number of specific micro-organisms and subsequent CHD, and prospective epidemiological studies have reported that elevated plasma levels of particular acute phase reactants (APRs) are predictors of future cardiac events. Investigators have also shown that immunisations exacerbate atherosclerosis in experimental animal models. These data raise the possibility that immunostimulation associated with natural infection by certain organisms, or vaccination, may promote atherosclerosis. A hypothesis which may explain all these findings, is that the cellular--and perhaps humoral--responses associated with immune stimulation may enhance atherogenesis.

Acute-Phase Proteins↗
PubMed1999

Immunization with bacillus Calmette-Guerin vaccine increases aortic atherosclerosis in the cholesterol-fed rabbit.

New Zealand White rabbits were injected subcutaneously with either a human dose of bacillus Calmette Guerin (BCG) vaccine (n = 7) or saline (n = 7). A further half dose of BCG or saline was injected after a further 4 weeks. The animals were subsequently fed a 0.25-1% cholesterol diet for 10 weeks, 8 weeks after the first injection. The rabbits were killed and perfusion fixed with 4% paraformaldehyde. The integrated plasma cholesterol levels did not differ significantly between the groups (P > 0.05). Plasma levels of anti-mycobacterial antibodies rose following BCG immunization, reaching a peak after 8 weeks (P < 0.05) compared to basal titers and the control group. BCG immunization was also associated with increased peripheral lymphocyte and monocyte activation, as evidenced by increased surface expression of IL-2 receptor (CD25) (P < 0.02) and MAC-I (CD11b) (P < 0.05), respectively. Significantly more mononuclear cells bound to the aortic endothelium of BCG immunized, cholesterol-fed rabbits (1.93+/-0.77 mononuclear cells/1000 endothelial cells) than to that of saline immunized rabbits (0.08+/-0.08 mononuclear cells/1000 endothelial cells; P < 0.01). The aortic intimal:medial ratio was greater in the BCG immunized rabbits (0.19+/-0.08) than those treated with saline (0.04+/-0.03; P < 0.05). This suggests that BCG immunization enhances peripheral leucocyte activation, aortic monocyte recruitment and atherogenesis in the cholesterol-fed rabbit.

Animals↗
PubMed1999

Dietary copper supplementation reduces atherosclerosis in the cholesterol-fed rabbit.

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. In the present study we have attempted to address this issue directly by investigating the effects of dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Age matched rabbits (n = 16) were fed a 0.25-1% cholesterol diet to maintain plasma cholesterol concentrations at approximately 30 mmol/l. Eight of these animals also received 0.2% copper acetate. Control animals (n = 8) received rabbit chow without supplements. After 13 weeks on the experimental diets the animals were killed. Integrated cholesterol levels were similar for the cholesterol-fed animals (31.1+/-2.5 vs. 29.9+/-1.9 mmol/l weeks; P>0.05). Although integrated plasma copper levels were higher in the animals receiving the copper supplements, these did not differ significantly (19.0+/-4.8 vs. 15.1+/-2.9 micromol/l weeks; P>0.05). Tissue concentrations of copper were higher in the copper fed animals compared to those on cholesterol alone in aortic 14.0+/-0.75 vs. 1.8+/-0.2 microg/g wet tissue; P<0.05), carotid artery (11.4+/-3.5 vs. 4.9+/-0.9 microg/g wet tissue; P<0.05), and hepatic (332.5+/-28.6 vs. 3.3+/-1.1 microg/g wet tissue; P<0.0001) samples. The concentration of copper within the carotid artery was also significantly higher than that within the aorta (7.5+/-1.8 vs. 2.4+/-0.4 microg/g wet tissue; P<0.05). In animals fed a normal rabbit chow aortic, carotid and hepatic copper concentrations were 3.7+/-0.8, 9.4+/-3.4, and 5.0+/-1.6 microg/g, respectively. These values did not differ significantly from the cholesterol-fed animals (P>0.05). Plasma concentrations of caeruloplasmin, the major copper carrying protein, were estimated as plasma ferroxidase activity and were similar for the groups (P>0.05), as were aortic superoxide dismutase activity levels (P>0.05). Copper supplementation was associated with increased mononuclear cell adhesion to the endothelium of the carotid endothelium, with 2.6+/-0.3 adherent monocytes/1000 endothelial cells in the cholesterol plus copper-fed animals compared to 1.3+/-0.3 in the cholesterol-fed group (P = 0.0006), and 0.1+/-0.1 in the control animals (P<0.002). This may reflect the higher concentrations of copper found within the carotid artery. Histology of the thoracic aorta at the level of the third and sixth intercostal arteries, showed that copper supplementation was associated with significantly smaller intimal lesions (P<0.05 and P<0.01, respectively). These data suggest that copper supplements possibly inhibit the progression of atherogenesis.

Animals↗
PubMed1999

Effects of vitamin E on human platelet and mononuclear cell responses in vitro.

Recent epidemiological studies have provided evidence supporting the potential benefits of antioxidants in coronary prevention. We have investigated the effects of vitamin E on platelets, monocytes and endothelial cells in vitro. Pre-incubation of platelets with vitamin E inhibited subsequent thrombin- (P < 0.05, n = 5), collagen- (P < 0. 0001, n = 5) and ADP-(P < 0.05, n = 4) induced platelet aggregation measured using a microtitre plate method, or conventional aggregometry. The adhesion of thrombin-activated platelets to collagen was also inhibited by vitamin E (P < 0.05, n = 8), but not by vitamin C (P > 0.05, n = 8); nor was the adhesion of unstimulated platelets significantly affected (P > 0.05, n = 8). Pre-incubation of monocytes with vitamin E inhibited their subsequent adhesion to plastic (P < 0.05, n = 9), and was also associated with an 18% reduction in adhesion to EA.hy 926 endothelial cells (n = 8), although this failed to reach statistical significance. Pre-incubation of the endothelial cells with vitamin E also significantly reduced subsequent mononuclear cell adhesion by 56% (P < 0.05, n = 3).

Adult↗
PubMed1999

Genetic markers to predict polygenic disease: a new problem for social genetics.

Many genetic markers that relate to common multifactorial disease in adults have been identified during the past 15 years. Their use as adjuncts for the diagnosis, prognosis, prediction of disease or targeting therapy for these disorders has begun, good examples being the Factor V Leiden mutation for venous-thromboembolism, lipoprotein lipase mutations for hypertriglyceridaemia and the apolipoprotein E4 variant for Alzheimer's dementia. However, extensive gene-gene and gene-environment interactions make their use more complex than markers for the simpler monogenic disorders (such as cystic fibrosis, or Duchenne's muscular dystrophy). Possible misapplication of the genetic markers for multifactorial disease in the fields of risk prediction, direct sales to the public, life assurance, employment rights, and legislation for regulation of their use are discussed.

Adult↗