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Biomedical subjects

E Grandone

Publications and source records attributed to E Grandone.

At least 55 records · Page 3Linked to original sources
PubMed1998

Prevalence of apolipoprotein E alleles in healthy subjects and survivors of ischemic stroke: an Italian Case-Control Study.

BACKGROUND AND PURPOSE: The epsilon4 allele of the apolipoprotein E (apoE) has been related to the occurrence of myocardial infarction, but its association with ischemic stroke is controversial. We have evaluated the relation between apoE alleles and the occurrence of cerebrovascular ischemia. METHODS: The apoE epsilon genotypes of 100 patients with a documented history of ischemic stroke without clinically apparent dementia (stroke+) and 108 subjects without such history (stroke-) were determined. The relative frequency of the apoE alleles and genotypes was estimated in 398 healthy subjects aged < 40 years from the same ethnic background. RESULTS: The frequency of the apoE epsilon4 allele in stroke+ (0.18 [95% CI, 0.12 to 0.25]) was higher than in stroke- (0.07 [95% CI, 0.03 to 0.12]; P<.001) or in healthy subjects (0.09 [95% CI, 0.07 to 0.12]; P<.001). Carriers of the epsilon4 allele differed between stroke+ (0.30 [95% CI, 0.19 to 0.42]) and stroke- (0.12 [95% CI, 0.5 to 0.22]; P=.004) or healthy subjects (0.16 [95% CI; 0.12 to 0.22]; P=.015). Accordingly, epsilon3/epsilon3 homozygotes were less frequent in stroke+ (0.59 [95% CI, 0.45 to 0.71]) than in stroke- (0.72 [95% CI, 0.59 to 0.82]; P=.063) or in healthy subjects (0.73 [95% CI, 0.67 to 0.78]; P=.01). In a multiple logistic regression analysis, age (P<.03), positive family history (P<.04) and apoE (P<.002) independently contributed to a stroke history, with epsilon4 carriers exhibiting a higher estimated risk (odds ratio, 5.05). CONCLUSIONS: Our data show an association between apoE gene and a personal history of ischemic stroke and support the possibility that the apoE gene is a susceptibility locus for the risk of cerebrovascular ischemic disease.

Adult↗
PubMed1998

The methylenetetrahydrofolate reductase TT677 genotype is associated with venous thrombosis independently of the coexistence of the FV Leiden and the prothrombin A20210 mutation.

A polymorphism, C-->T677, in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified as a cause of mild hyperhomocysteinemia, a risk factor for venous thrombosis. We have investigated the frequency of the TT genotype in 277 consecutive patients with confirmed deep venous thrombosis and 431 healthy subjects. The TT MTHFR genotype was more frequent in patients than in controls (25.6% vs. 18.1%; p = 0.016). The risk of thrombosis among carriers of this genotype was significantly increased [odds ratio: 1.6 (95% CI: 1.1-2.3)]. The estimated risk associated with the TT genotype was 2.0 (95% CI: 1.3-3.1) in subjects with (n = 122), and 1.3 (95% CI: 0.8-2.0) in those without (n = 155) predisposing (hereditary, acquired or circumstantial) risk factors for venous thrombosis. Factor V Leiden and prothrombin G-->A20210 are known risk factors for venous thrombosis. After stratification for FV Leiden and prothrombin A20210 mutations, a significant association was also observed. After adjustment for sex, FV Leiden and prothrombin A20210 mutation, the estimated risk of venous thrombosis among carriers of the TT MTHFR genotype was 1.7 (95% CI: 1.2-2.6). The TT MTHFR genotype is independently associated with venous thrombosis, mainly among individuals with a high risk profile.

Adolescent↗
PubMed1998

Reduction of mononuclear cytokine production in hemodialysis patients treated with steam-sterilized low-flux polysulphone membranes.

An increased cytokine production, correlated with long term complications of uremic disease, has been described during hemodialysis. To identify possible differences in the cytokine release of differently sterilized membranes, we enrolled six uremic patients on chronic hemodialysis. The patients underwent dialysis with ETO-sterilized low-flux polysulphone membranes (F6, Fresenius AG) for at least three months (A1), they were then switched to steam-sterilized polysulphone membranes (F6-HPS Fresenius AG) and further evaluations after one (B1) and two months (B2) were carried out. A final evaluation (A2) was made one month after switching back to F6 dialyzers. At each time period, samples were drawn to measure IL-1beta released by cultured mononuclear cells (MN). Moreover, dialysate samples were collected to test endotoxin levels. C3a and C5a levels were assessed at 0, 5, 15 and 60 min from starting hemodialysis. Anti-ETO IgE levels were also assayed at A1, B1 and A2. The LAL test revealed a good quality dialysate. The mean pre-dialysis IL-1beta levels were 215 pg/million cells at A1; falling to 49 at B1, and 54 at B2 (p<0.01); there was then a sharp rebound at A2: 284, p<0.01. Post-dialysis levels followed the same pattern. No correlation between the dialysate endotoxin level and cytokine release was found. Complement activation did not change and in all the phases of the study no anti-ETO IgE was detected in any of the subjects. Our data suggest that the steam sterilized polysulphone membrane induces a lower cytokine release than the ETO sterilized membrane, although the mechanism by which it does so remains to be clarified.

Adult↗
PubMed1998

Fibrinogen plasma levels in an apparently healthy general population--relation to environmental and genetic determinants.

Elevated fibrinogen levels are an independent risk factor for cardiovascular ischemic disease. We investigated the relationship between cardiovascular ischemic risk factors, the fibrinogen Bbeta-chain G/A(-455) polymorphism and plasma fibrinogen levels in 989 apparently healthy subjects. Fibrinogen values were higher in subjects with C reactive protein (C-RP) >0.33 mg/dl, BMI >23.9 kg/m2, total cholesterol >4.84 mmol/l, triglycerides > 1.02 mmol/l, PAI-1 antigen >12.2 ng/ml, carriers of the A allele, first-degree relative history of coronary artery disease, or consuming >10 cigarettes per day (p<0.01). Men and ethanol drinkers showed lower plasma fibrinogen levels (p<0.01). The multivariate analysis confirmed the independent effect of C-RP, age, BMI, total cholesterol, gender, PAI-1, -455 G/A polymorphism, (p<0.05). BMI, total cholesterol, PAI-1, alcohol and smoking habit raised with the increase of age and differed between sexes. The A(-455) allele increasing effect was significant in women, especially in subjects aged <30 years, and in men aged <43 years. These results indicate that environmental factors contributed to a larger extent to fibrinogen variability, whereas the A(-455) allele was associated with a steeper increase in younger age quartiles.

Adult↗
PubMed1997

Plasminogen activator inhibitor-1 (PAI-1) antigen plasma levels in subjects attending a metabolic ward: relation to polymorphisms of PAI-1 and angiontensin converting enzyme (ACE) genes.

Plasminogen activator inhibitor 1 (PAI-1) is a determinant of vascular events. Subjects in metabolic wards are at high risk for these events. The renin-angiotensin system modulates plasma PAI-1 levels. An insertion (4G)/deletion (5G) polymorphism is involved in the regulation of the circulating levels of PAI-1. We have evaluated the levels of plasma PAI-1 in 208 individuals from our metabolic ward and correlated these levels with the 4G/5G genotype as well as with a genotype (homozygosity for a deletion polymorphism, DD genotype) of the angiotensin-converting enzyme (ACE) gene. Homozygosity for the insertion genotype (5G/5G) was associated with PAI-1 levels lower than those associated with the deletion genotype (4G/4G) (26.2x/:1.6 versus 33.7x/:1.7 ng/mL, P = .036). Plasma PAI-1 levels appeared to depend on the genotype (P = .014) as much as on age (P = .044), t-PA (P = .0001), or triglyceride levels (P = .005). The association between triglycerides and PAI-1 was significant in subjects carrying the 4G/4G and the 4G/5G genotypes (P = .013 and .036, respectively) but not in those with the 5G/5G genotype. When stratified according to PAI-1 and ACE genotypes, individuals homozygous for both deletions (4G/4G-DD genotypes) exhibited higher plasma PAI-1 levels compared with those of individuals without such homozygosities. However, this difference did not reach statistical significance. We conclude that in a group of subjects from a metabolic ward, a 4G/5G polymorphism of the PAI-1 gene exerts effects on plasma PAI-1 antigen levels comparable to those of established determinants. The association between triglycerides and plasma PAI-1 levels is genotype dependent. A trend to a positive interaction between ACE DD and PAI-1 4G/4G in the regulation of circulating plasma PAI-1 levels is present in this setting.

Adult↗
PubMed1997

Factor V Leiden is associated with repeated and recurrent unexplained fetal losses.

Activated protein C resistance (APCR) is responsible for most cases of familial thrombosis. The factor V missense mutation Arg506 > Gln (FV Leiden) has been recognized as the commonest cause of this condition. Recently, it has been suggested that APCR is associated with second trimester fetal loss. We investigated the distribution of FV Leiden in a sample (n = 43) of Caucasian women with a history of two or more unexplained fetal losses. A group (n = 118) of parous women with uneventful pregnancies from the same ethnical background served as control. We found the mutation in 7 cases (16.28%) and 5 controls (4.24%; p = 0.011). A statistically significant difference between women with only early fetal loss vs those with late events (p = 0.04) was observed. Our data demonstrate a strong association between FV Leiden and fetal loss. Furthermore, they indicate that late events are more common in these patients.

Abortion, Habitual↗
PubMed1997

Clinical relevance of polymorphic markers of arterial thrombosis.

Case-control and cross-sectional studies show that some common molecular variations (polymorphisms) of genes coding for proteins involved in atherosclerosis and thrombosis are often present in subjects who have experienced cerebrovascular or cardiovascular events. The clinical impact of the majority of polymorphic markers is disputed by prospective reports. In contrast, their pathophysiological implications and their role in monitoring parameters that are difficult to be checked by alternative means, are documented by the large majority of the reports. From the evidence available, there may be suggestion for further impact of polymorphic markers in vascular medicine. To substantiate this, new prospective studies that include individuals from different geographical areas and that take into account the statistical power, the informativeness of the markers, the coexistance of established risk factors and the genetic background of the populations analyzed, are urgently needed.

Chromosome Mapping↗
PubMed1997

Factor V Leiden, C > T MTHFR polymorphism and genetic susceptibility to preeclampsia.

We performed a case-controlled study to investigate whether the FV Leiden mutation and the C > T677 polymorphism of the 5, 10 methylene tetrahydrofolate reductase (MTHFR) are associated with the occurrence of preeclampsia in 96 otherwise healthy preeclamptic women and 129 parous women as controls. FV Leiden carriers were 10 (10.5%) in cases and 3 (2.3%) in controls (OR: 4.9, 95% CI: 1.3-18.3). MTHFR TT homozygotes were 28 (29.8%) in cases and 24 (18.6%) in the control group (OR: 1.8, 95% CI 1.0-3.5). No difference in any of the polymorphisms was found between proteinuric (n = 45) and non-proteinuric (n = 51) patients. Moreover, MTHFR polymorphism does not affect the association between FV Leiden and preeclampsia. In conclusion, FV Leiden mutation and MTHFR TT genotype are associated with the occurrence of preeclampsia, suggesting that, during pregnancy, women carrying these gene variants are prone to develop such a complication.

Adolescent↗
PubMed1996

Drugs affecting plasma fibrinogen levels. Implications for new antithrombotic strategies.

Current evidence indicates that plasma fibrinogen is synthesized by the liver; that genetic and environmental factors regulate plasma fibrinogen levels; that interleukin-6 (IL-6) affects the synthesis of plasma fibrinogen by mechanisms involving protein kinase C, and that during the acute-phase response, monocytes generate a variety of monokines including IL-6. Certain drugs and nutrients have been reported to lower plasma fibrinogen levels. The mechanism(s) involved in this effect is poorly understood. However, since most of these substances quantitatively and/or qualitatively affect monocytes, the possibility that these drugs affect plasma fibrinogen levels via these cells should be considered. In addition to fibrinogen, IL-6 also regulates the synthesis of other acute-phase proteins. Especially when combined, major risk factors for atherosclerosis cause vascular injury that triggers inflammatory events. This raises the issue of whether high plasma fibrinogen levels are just the epiphenomenon of as yet unknown events in thrombosis and atherosclerosis. Thus, the issue to be addressed is whether high plasma fibrinogen concentrations should be lowered or should they serve to suggest strong interventions on established risk factors. As for other risk factors, fibrinogen measurements in population-based studies, in parallel with measurements of established risk factors will help define appropriate directions to be followed to gain insight into the issue and define new antithrombotic strategies.

Animals↗
PubMed1996

Genetic Modulation of Plasma Fibrinogen Concentrations: Possible Importance of Interleukin-6.

Current knowledge indicates that high plasma levels of fibrinogen, a key protein in the hemostatic system, help predict the major ischemic complications of atherosclerosis, that is, stroke and myocardial infarction. Molecular variations at the fibrinogen genes loci have been shown to regulate fibrinogen concentrations in plasma. However, it is also known that fibrinogen is an acute phase reactant and that its plasma levels are increased by the inflammatory mediator interleukin-6 (IL-6) as a consequence of stimulated gene expression. Certain risk factors for atherosclerosis are known to cause inflammatory and proliferative events within the vessel wall, especially when combined. This raises the question of whether and to what extent high plasma fibrinogen levels in patients with major thrombotic complications of atherosclerosis could be the epiphenomena of as yet poorly elucidated issues in vascular medicine (i.e., severity of vascular damage). Screening of the fibrinogen genes loci in both young patients with established risk factors and in patients evaluated for regression of atherosclerosis who have participated in risk factor reduction programs may provide further insight into the role of genetic factors in the development of atherosclerosis and in the regulation of plasma fibrinogen levels.

Journal Article↗
PubMed1996

Plasma lipoprotein(a) levels in subjects attending a metabolic ward. Discrimination between individuals with and without a history of ischemic stroke.

In this cross-sectional study we compared the abilities of lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (TPA) to discriminate between individuals with and without a history of stroke from among subjects in a metabolic ward. A total of 210 subjects (108 men and 102 women; mean age, 63.8 years; range, 31 to 86 years) provided plasma and DNA samples for the study. Of these, 51 men and 50 women had a history of ischemic stroke. The 109 subjects without a history of stroke were compared with those with such a history for major risk factors for ischemic events. Mean plasma TPA and PAI-1 levels significantly (P < .001) discriminated among subjects younger than 70 years with a history of stroke. The mean plasma Lp(a) level of stroke subjects (21.9 mg/dL) did not differ significantly from that of control subjects (15.2 mg/dL). However, among individuals < 70 years old, Lp(a) plasma levels > 50 mg/dL were more common among stroke patients (8 with versus 1 without, P < .01 by chi 2 test). A molecular variation in the 5' flanking region of the apo(a) gene that has been related to elevated Lp(a) plasma levels (G/A-914) was not strongly correlated with circulating levels of Lp(a), nor did Lp(a) levels correlate with a polymorphism of the apo(a) gene (G/A-21), which is strongly linked (P < .001) to the G/A-914 variation. In this setting, the relation between Lp(a) and cerebral ischemia appears to be limited to individuals below 70 years with elevated (> 50 mg/dL) plasma levels of the lipoprotein.

Adult↗
PubMed1996

Deletion polymorphism in the angiotensin-converting enzyme gene in patients with a history of ischemic stroke.

We evaluated the genotypes of the angiotensin-converting enzyme (ACE) gene in 101 subjects with and 109 subjects without a history of ischemic stroke. All were attending a metabolic ward. The two groups were compared for major risk factors for ischemic events. Genotypes were determined by polymerase chain reaction with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene. Deletion polymorphism of the ACE gene (DD genotype) was shown to be more common in subjects with a history of stroke than in those without (relative risk, 1.76; confidence intervals, 1.02 to 3.05). A positive family history for ischemic complications of atherosclerosis was also more common in subjects with documented events (relative risk, 1.99; confidence intervals, 1.10 to 3.59). DD genotype and a positive family history were strong independent discriminators of cerebral ischemia. Plasma levels of tissue-type plasminogen activator (TPA) and plasminogen activator inhibitor-1 help identify subjects with a history of cerebral ischemic episodes. When such fibrinolytic variables were included in the analysis, the DD genotype still strongly and independently discriminated subjects with a stroke history and significantly interacted with TPA levels > 10 ng/mL in such identification. We conclude that in subjects attending a metabolic ward, homozygosity for a deletion polymorphism of the ACE gene consistently discriminates subjects with a stroke history. Interaction with TPA improves such identification.

Adult↗
PubMed1996

Ethylene-oxide and steam-sterilised polysulfone membrane in dialysis patients with eosinophilia.

Eosinophilia and some acute dialysis side-effects, such as itching, flushing and bronchospasm, are often associated with the presence of ethylene oxide (ETO) as dialyzer sterilizing agent. This study evaluated the effects of two different polysulfone (PS) hollow-fiber dialysers sterilized with ETO and steam in 31 chronic dialysis patients with eosinophilia. Clinical symptoms, metabolic and biochemical parameters, complement (C3a and C5a) activation and production were evaluated in each patient dialysed for two months at a time with Cuprophan dialyser, ETO-PS dialyser and steam-PS dialyser. The steam-sterilizer agent does not alter the purifying capacity of the PS membrane which maintains its superiority over Cuprophan in terms of biocompatibility. Using steam-PS, intradialytic eosinophil kinetics seems to improve. In some patients with high serum levels of ETO-specific IgE these levels tend to diminish. Generic intradialytic symptoms do not differ between the two sterilization methods, although some hypersensitivity symptoms during the first dialysis hour are considerably lower in some patients when steam-sterilized PS is used.

Adult↗