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Biomedical subjects

D S O'Reilly

Publications and source records attributed to D S O'Reilly.

At least 19 recordsLinked to original sources
PubMed2001

Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein--a cross-sectional population survey.

The effects of hormone replacement therapy (HRT) on thrombosis risk, thrombotic variables, and the inflammatory marker C-reactive protein (CRP) may vary by route of administration (oral versus transdermal). We studied the relationships of 14 thrombotic variables (previously related to cardiovascular risk) and CRP to menopausal status and to use of HRT subtypes in a cross-sectional study of 975 women aged 40-59 years. Our study confirmed previously-reported associations between thrombotic variables and menopausal status. Oral HRT use was associated with increased plasma levels of Factor IX, activated protein C (APC) resistance, and CRP; and with decreased levels of tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity. Factor VII levels were higher in women taking unopposed oral oestrogen HRT. The foregoing associations were not observed in users of transdermal HRT; hence they may be consequences of the "first-pass" effect of oral oestrogens on hepatic protein synthesis. We conclude that different effects of oral and transdermal HRT on thrombotic and inflammatory variables may be relevant to their relative thrombotic risk; and suggest that this hypothesis should be tested in prospective, randomised studies.

Activated Protein C Resistance↗
PubMed2000

Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group.

BACKGROUND: Chronic inflammation is believed to increase the risk of coronary events by making atherosclerotic plaques in coronary vessels prone to rupture. We examined blood constituents potentially affected by inflammation as predictors of risk in men with hypercholesterolemia who were enrolled in the West of Scotland Coronary Prevention Study, a trial that evaluated the value of pravastatin in the prevention of coronary events. METHODS: A total of 580 men who had had a coronary event (nonfatal myocardial infarction, death from coronary heart disease, or a revascularization procedure) were each matched for age and smoking status with 2 control subjects (total, 1160) from the same cohort who had not had a coronary event. Lipoprotein-associated phospholipase A2, C-reactive protein, and fibrinogen levels, and the white-cell count were measured at base line, along with other traditional risk factors. The association of these variables with the risk of coronary events was tested in regression models and by dividing the range of values according to quintiles. RESULTS: Levels of C-reactive protein, the white-cell count, and fibrinogen levels were strong predictors of the risk of coronary events; the risk in the highest quintile of the study cohort for each variable was approximately twice that in the lowest quintile. However, the association of these variables with risk was markedly attenuated when age, systolic blood pressure, and lipoprotein levels were included in multivariate models. Levels of lipoprotein-associated phospholipase A2 (platelet-activating factor acetylhydrolase), the expression of which is regulated by mediators of inflammation, had a strong, positive association with risk that was not confounded by other factors. It was associated with almost a doubling of the risk in the highest quintile as compared with the lowest quintile. CONCLUSIONS: Inflammatory markers are predictors of the risk of coronary events, but their predictive ability is attenuated by associations with other coronary risk factors. Elevated levels of lipoprotein-associated phospholipase A2 appear to be a strong risk factor for coronary heart disease, a finding that has implications for atherogenesis and the assessment of risk.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

Changes in micronutrient concentrations following anti-inflammatory treatment in patients with gastrointestinal cancer.

Circulating concentrations of vitamin antioxidants (retinol, alpha-tocopherol, lutein, lycopene, alpha- and beta-carotene) and trace elements (zinc, copper, iron and selenium) plus carrier proteins (albumin, transferrin, caeruloplasmin) in gastrointestinal cancer patients (n = 12) with an inflammatory response (as demonstrated by an elevated C-reactive protein concentration) were compared with a control group (n = 12). Further, the effect of moderating the inflammatory response, using the anti-inflammatory agent ibuprofen, on these measurements was examined in the cancer group. The control and cancer groups were similar in terms of age, sex, and body mass index. However, the cancer group had significantly higher C-reactive protein concentrations (P < 0.001). Concentrations of vitamin antioxidants and trace elements (and carrier proteins) were significantly lower (P < 0.001), except copper (ceruloplasmin) which was significantly higher (P < 0.05). After anti-inflammatory treatment, there were small but significant increases in lutein, lycopene, and beta-carotene (P < 0.05) and in iron and selenium (P < 0.05), whereas ceruloplasmin decreased (P < 0. 05). The micronutrient concentrations in the cancer patients remained different from those in the control subjects. These results support the concept that the magnitude of inflammation plays an important role in the regulation of circulating concentrations of vitamin antioxidants and trace elements in patients with gastrointestinal cancer.

Adrenal Cortex Hormones↗
PubMed2000

Postprandial response to a fat tolerance test in young adults with a paternal history of premature coronary heart disease - the EARS II study (European Atherosclerosis Research Study).

BACKGROUND: The European Atherosclerosis Research Study (EARS) I had shown that fasting plasma concentrations of apolipoprotein B (apo B) and triglycerides were the most discriminant variables between offspring with a paternal history of coronary heart disease (CHD) and controls. The EARS II study was undertaken to investigate whether a paternal history of CHD was associated with differences in postprandial lipemia. DESIGN: Male subjects with a paternal history of CHD (cases, n = 407) and age-matched male controls (n = 415) were recruited from 14 European universities. All subjects had an oral fat tolerance test. RESULTS: In the sample as a whole, the postprandial triglyceride responses did not significantly differ between the two groups. However, in the upper tertile of fasting triglycerides, cases displayed a higher area under the curve (5.71 vs. 4.49 mmol.h L-1, P < 0.001), a higher peak (1.76 vs. 1.43 mmol L-1, P < 0.001) and a more delayed time to peak (3.15 vs. 2.91 h, P < 0.05) than controls. In the upper tertile, fasting apo B levels (P < 0.05) and triglyceride area under the curve (P = 0.002) significantly discriminated cases from controls in a multivariate analysis. Cases had also higher Lp C-III:B levels at 4 h than controls (11.2 vs. 9.9 mg dL-1, P < 0.01) and this difference remained significant after adjustment for apo B and triglyceride levels. CONCLUSIONS: These results indicate that in subjects with a moderate elevation of fasting triglycerides, an impaired postprandial response to a fat load constitutes an early biological expression of a paternal history of premature CHD.

Administration, Oral↗
PubMed2000

ACP Best Practice No 163. Wilson's disease: acute and presymptomatic laboratory diagnosis and monitoring.

Wilson's disease, the most common inherited disorder of copper metabolism, is a recessive genetic condition. The clinical presentation of Wilson's disease is very variable. It is characterised by low serum copper and caeruloplasmin concentrations coupled with the pathological accumulation of copper in the tissues. However, there are diagnostic difficulties and these are discussed. The current value of DNA diagnosis, both in gene tracking in families or as applied to de novo cases, is examined. Wilson's disease can be treated successfully but treatment must be life long. Patients are best treated by specialist centres with experience and expertise in the condition.

Biomarkers↗
PubMed1999

Effect of apo E phenotype on plasma postprandial triglyceride levels in young male adults with and without a familial history of myocardial infarction: the EARS II study. European Atherosclerosis Research Study.

The goal of the present study was to assess whether the effect of the apolipoprotein E polymorphism on postprandial lipemia explained part of the risk attributable to familial history of coronary heart disease. Cases (n = 407) were students, aged between 18 and 28 years, whose fathers had a proven myocardial infarction before the age of 55 years. Age-matched controls (n = 415) were recruited from the corresponding student registers. Blood was obtained after an overnight fast and at 2, 3, 4 and 6 h after ingestion of a fatty meal for triglyceride measurements. Apolipoprotein E phenotype was associated with postprandial triglyceride variability in both cases and controls. However, the apolipoprotein E-dependent triglyceride response was not significantly heterogeneous between cases and controls. In the pooled data, postprandial triglyceride levels were higher in carriers of the E2 and, to a lesser extent, of the E4 isoform, than in E3/3 homozygotes, independently of fasting triglyceride levels. At 6 h, triglyceride levels were increased by 21.2% (P < 0.01) in E2 carriers and 11.5% (P = 0.053) in E4 carriers by comparison to E3/3 subjects. These effects were not significantly different between regions. In conclusion, the effects of the apolipoprotein E polymorphism on postprandial triglyceridemia are similar across regions of Europe, and homogeneous in healthy young subjects with and without a family history of early myocardial infarction. This suggests that the influence of apolipoprotein E on myocardial infarction risk may be acting through mechanisms other than through effects on postprandial triglyceridemia.

Adolescent↗
PubMed1998

A routine method for the simultaneous measurement of retinol, alpha-tocopherol and five carotenoids in human plasma by reverse phase HPLC.

We describe a simple isocratic HPLC method for the accurate and precise measurement of retinol, alpha-tocopherol and the major carotenoids in plasma using UV detection. Reference ranges for retinol, alpha-tocopherol and five carotenoids are determined in a healthy population group. The most abundant carotenoids found in plasma were beta-carotene, lycopene, lutein and cryptoxanthin. Retinol, alpha-tocopherol and carotenoids were determined simultaneously using two internal standards, retinol acetate for retinol and tocopherol acetate for alpha-tocopherol and carotenoids. The use of echinenone as an internal standard for carotenoids was investigated. The protective effect of an antioxidant (ascorbic acid) on the stability of samples and extracted material is documented. The method is useful for the routine measurement of plasma retinol, alpha-tocopherol and carotenoids and could also be used in large scale epidemiological studies.

Adult↗
PubMed1998

Alteration of the circadian rhythm of intact parathyroid hormone and serum phosphate in women with established postmenopausal osteoporosis.

Several studies have established that the circulating concentration of intact parathyroid hormone, PTH (1-84), over 24 h follows a circadian rhythm. The importance of this circadian rhythm is not known although some authors have detected alterations in the rhythm in metabolic bone disease and following dietary manipulation. We have studied the circadian rhythm of PTH (1-84) in 8 premenopausal women, 8 postmenopausal women with established osteoporosis and 8 postmenopausal women with no evidence of osteoporosis. Blood samples were obtained at 30-min intervals over a 24-h period and significant differences were found in the profiles of PTH (1-84) and serum phosphate in the three groups studied. Premenopausal women possessed a nocturnal/early morning increase in PTH (1-84) and phosphate (between 2200 and 0700 hours), as did postmenopausal women without osteoporosis. In postmenopausal women with osteoporosis the nocturnal increase in PTH (1-84) and serum phosphate was absent and PTH (1-84) decreased during the period 2200-0700 hours. A shift in acrophase is observed between premenopausal and postmenopausal women without osteoporosis. No acrophase was found in postmenopausal women with osteoporosis for either PTH (1-84) or serum phosphate. No circadian rhythm, acrophase or significant amplitude was observed in serum adjusted calcium or ionized calcium in any group studied. Alterations in the circadian rhythms for PTH (1-84) and serum phosphate occur in patients with postmenopausal osteoporosis that suggest that normal dynamics of PTH (1-84) secretion may play a role in both calcium and phosphate metabolism and the bone remodelling process. Whether these changes are causative or a response to the pathology will require further investigation.

Adult↗
PubMed1998

Influence of polymorphism Q3405E and mutation A3371V in the apolipoprotein B gene on LDL receptor binding.

Familial defective apolipoprotein B (FDB) is due to mutations in the apolipoprotein B (apo B) gene at codon 3500 or 3531 that affect low density lipoprotein (LDL) receptor binding. From sequence analysis the putative receptor binding site was believed originally to be upstream from this at residues 3147-3157 and 3357-3367. Using denaturing gradient gel electrophoresis, mutations were sought in codons 3350-3466. This includes the important positively charged residues 3357-3367. DNA from 928 hyperlipidaemic individuals was studied and two hitherto unknown DNA changes were discovered, one of which resulted in an altered amino acid in the apo B. A known polymorphism Q3405E was also detected at a carrier frequency of 1.4%. Using growth of U937 cells as a measure of binding affinity of LDL to its receptor the newly discovered mutant A3371V permitted the same growth as LDL from normolipidaemic individuals of the U937 cells, however, the LDL from Q3405E individuals permitted only 77% of the normal growth (P=0.009).

Adult↗
PubMed1997

Acute-phase reactants and plasma trace element concentrations in non-small cell lung cancer patients and controls.

This study examined the effect of an acute-phase response on plasma trace element concentrations of non-small cell lung cancer (NSCLC) patients. In normal subjects (n = 13) and NSCLC patients (n = 22), fasting concentrations of albumin, C-reactive protein, the trace elements iron, zinc, copper, and selenium, and their associated proteins transferrin, albumin, ceruloplasmin, and glutathione peroxidase were measured. The NSCLC patients were subdivided into two equal groups depending on whether they had a C-reactive protein concentration < 35 mg/l (Group 1) or > 35 mg/l (Group 2). Circulating zinc, iron, and transferrin concentrations were significantly lower in NSCLC Group 1 than in the control group (p < 0.05). Circulating concentrations of iron, zinc, and the binding proteins transferrin and albumin were significantly lower in NSCLC Group 2 than in the control group and NSCLC Group 1 (zinc not significantly different) (p < 0.01). In contrast circulating concentrations of copper and its binding protein ceruloplasmin were significantly increased in NSCLC Group 2 compared with NSCLC Group 1 and the control group (p < 0.01). Additionally, plasma selenium and glutathione peroxidase concentrations were significantly lower (p < 0.05) in NSCLC Group 2 than in NSCLC Group 1 and the control group. In the NSCLC patients there were significant negative correlations between concentrations of C-reactive protein and iron, transferrin, zinc, albumin, and selenium (p < 0.05). Furthermore, there were also significant positive correlations between C-reactive protein and copper (r = 0.788, p < 0.001) and ceruloplasmin (r = 0.831, p < 0.001) concentrations. The presence of an acute-phase response has implications for the interpretation of circulating trace element concentrations, the status of patients with NSCLC, and supplementation with trace elements in patients with NSCLC.

Acute-Phase Proteins↗
PubMed1997

Effect of inflammation on measures of antioxidant status in patients with non-small cell lung cancer.

This study examined the effect of an inflammatory response on measures of antioxidant status in patients with non-small cell lung cancer (NSCLC). In healthy, control subjects (n = 13) and NSCLC patients (n = 22) fasting concentrations of albumin, C-reactive protein, cholesterol, and the antioxidants alpha-tocopherol, retinol, lutein, lycopene, and alpha- and beta-carotene were measured. The two groups were similar in terms of age, sex, and body mass index. However, the cancer group had an inflammatory response as evidenced by significantly increased C-reactive protein concentrations. Concentrations of all the measured antioxidants of the NSCLC group were significantly lower than those of the control group (P < 0.01). The lowest concentrations were those of the carotenoids lycopene and alpha- and beta-carotene. In the cancer group there were significant negative correlations between concentrations of C-reactive protein and retinol (r = -0.682, P < 0.01), alpha-tocopherol (r = -0.464, P < 0.05), and lutein (r = -0.599, P < 0.01). The results of this study have implications for the interpretation of circulating antioxidant concentrations in patients with NSCLC.

Aged↗
PubMed1997

Interactions between lifestyle-related factors and the ApoE polymorphism on plasma lipids and apolipoproteins. The EARS Study. European Atherosclerosis Research Study.

To elucidate how the apolipoprotein (apo) E polymorphism and modifiable factors interact in explaining plasma lipid and apolipoprotein levels, we studied 1448 young adults (18 to 26 years old), participating in the European Atherosclerosis Research Study (EARS). Venous blood was collected after an overnight fast. Modifiable factors, eg, body mass index (BMI), waist-to-hip ratio (WHR), tobacco and alcohol consumption, and physical activity, were determined by using standardized protocols. Associations of modifiable factors with apoE levels were homogeneous across apoE phenotypes. In contrast, correlations of BMI with total cholesterol and apoB levels, as well as correlations between WHR and apoB, were significantly (P < .05 to P < .01) stronger in E2 carriers than in subjects with other phenotypes. Total cholesterol and apoB levels were comparable in E2 carriers in the upper tertile of BMI or WHR to those in E3/3 subjects, suggesting that the lowering effect of the E2 allele was no longer present. The inverse association between the plasma cholesteryl linoleate-to-oleate ratio, a marker for the dietary polyunsaturated-to-saturated fatty acid ratio, and triglycerides was also stronger in E2 carriers (-0.33 versus -0.17 in E3/3 and -0.24 in E4 carriers). Associations with other modifiable factors were notably consistent across apoE phenotypes. Gender and modifiable factors explained three times more (31%) of the interindividual variation in apoB levels in E2 carriers than in E3/3 subjects (9%) or E4 carriers (14%), mainly due to a larger variance explained by BMI. Our results suggest that the apoE polymorphism acts in a relatively uniform manner, independently of lifestyle. However, the associations of adiposity to total cholesterol and apoB levels appear to be stronger in apoE2 carriers.

Adolescent↗