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Biomedical subjects

E Taioli

Publications and source records attributed to E Taioli.

At least 55 records · Page 3Linked to original sources
PubMed1999

The G20210A mutation of the prothrombin gene in patients with previous first episodes of deep-vein thrombosis: prevalence and association with factor V G1691A, methylenetetrahydrofolate reductase C677T and plasma prothrombin levels.

A common G to A transition at nucleotide 20210 of the prothrombin gene is associated with an increased risk for deep-vein thrombosis (DVT) and high plasma levels of prothrombin. We calculated the prevalences of prothrombin G20210A, factor V G1691A (also associated with high risk for DVT) and homozygous methylenetetrahydrofolate reductase (MTHFR) C677T (associated with increased susceptibility to develop hyperhomocysteinemia) in 118 patients with a first episode of DVT and in 416 healthy controls. 15.9% of the patients and 2.3% of the controls had prothrombin G20210A (odds ratio [OR]: 8.7, 95% C.I.: 3.8-21.4); 21.1% of the patients and 3.2% of the controls had factor V G1691A (OR 7.8, 3.9-17.1); 20.5% of the patients and 21% of the controls had homozygous MTHFR C677T (OR: 1.0, 0.7-1.2). Exclusion of patients with other hereditary risk factors for DVT did not substantially modify the results. Mutant factor V and prothrombin coexisted in three patients but in no control. The concomitant presence of the MTHFR mutation did not increase the thrombotic risk associated with prothrombin G20210A. 63.2% of individuals with prothrombin G20210A had plasma levels of prothrombin in the upper quartile of distribution. After adjustment for age and sex, subjects with prothrombin levels in the upper quartile carried a slightly higher risk for thrombosis than those with lower prothrombin concentrations (OR: 1.9, 1.1-3.2). In conclusion, we found that prothrombin G20210A is relatively common in Italy and is associated with high prothrombin levels and an 8.7-fold increase in the risk for DVT. Such risk is independent of the coexistence of other known inherited risk factors for thrombosis and increases in patients with associated mutant factor V. Whether it is due to the associated increase in plasma prothrombin levels remains to be established.

Adolescent↗
PubMed1999

Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk.

The endogenous metabolism of estrogens is primarily oxidative and involves hydroxylation of the steroid at either C2 (2-OHE1) or C16 (16-OHE1). While the 2-OHE1 metabolites are essentially devoid of peripheral biological activity, 16-OHE1 is an estrogen agonist. There is evidence of an association between the 2-OHE1/16-OHE1 metabolites ratio and breast cancer risk. The CYP1A1 gene may play a role in the 2-hydroxylation (2-OH) of estradiol. African-American women with the wild-type CYP1A1 gene showed a significant increase in the 2-OHE1/16-OHE1 ratio, from 1.35 +/- 0.56 at baseline to 2.39 +/- 0.98 (p = 0.006) after 5 days of treatment with indole-3-carbinol (400 mg/day), a 2-OHE1 inducer. Women with the Msp1 polymorphism showed no significant increase, (0.37% +/- 0.17%). In a case-control study involving 57 women with breast cancer and 312 female controls, the frequency of the homozygous Msp1 polymorphism was 4.2% in African-American controls and 16% in African-American breast cancer cases. The odds ratio of breast cancer with the Msp1 homozygous variant was 8.4 (95% confidence interval: 1.7-41.7). This association was not observed in Caucasian women. The other CYP1A1 polymorphisms were not associated with breast cancer. The CYP1A1 Msp1 polymorphism may be a marker of altered estradiol metabolism and of increased susceptibility to estrogen-related breast cancer in African-Americans.

Adult↗
PubMed1999

Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis.

Single-point mutations in the gene coding for prothrombin (factor II:A20210) or factor V (factor V:A1691) are associated with an increased risk of venous thromboembolism. The use of oral contraceptives is also a strong and independent risk factor for the disease, and the interaction between factor V:A1691 and oral contraceptives greatly increases the risk. No information is available about the interaction between oral contraceptives and mutant prothrombin. We investigated 148 women with a first, objectively confirmed episode of deep vein thrombosis and 277 healthy women as controls. Fourteen patients (9.4%) were carriers of factor II:A20210, 24 (16.2%) of factor V:A1691, and 4 (2.7%) of both defects. Among controls, the prevalence was 2.5% for either factor II:A20210 or factor V:A1691, and there was no carrier of both the mutations. The relative risk of thrombosis was 6-fold for factor II:A20210 and 9-fold for factor V:A1691. The most prevalent circumstantial risk factor in patients and the only one observed in controls was oral contraceptive use, which per se conferred a 6-fold increased risk of thrombosis. The risk increased to 16.3 and 20.0 when women with factor II:A20210 or factor V:A1691 who used oral contraceptives were compared with noncarriers and nonusers. These figures indicate a multiplicative interaction between the genetic risk factors and oral contraceptives. No difference in the type of oral contraceptives was observed between patients and controls, those of third generation being the most frequently used (73% and 80%). We conclude that carriers of the prothrombin mutation who use oral contraceptives have a markedly increased risk of deep vein thrombosis, much higher than the risk conferred by either factor alone.

Adolescent↗
PubMed1999

Genetic risk factors for superficial vein thrombosis.

Inherited thrombophilic states are associated with an increased risk for deep vein thrombosis (DVT), but whether they are also risk factors for superficial vein thrombosis (SVT) is uncertain. We assessed the risk conferred by inherited thrombophilic states in patients with a first episode of SVT in whom the coexistence of DVT had been ruled out by ultrasonography. Sixty-three patients with SVT, after exclusion of patients with varicose veins, malignant or autoimmune disease, and 537 healthy individuals were investigated. The G1691A mutation in the factor V gene, the G20210A mutation in the prothrombin gene, and deficiencies of the naturally occurring inhibitors of coagulation (antithrombin, protein C, protein S) were searched. The prevalence of each thrombophilic state was higher in patients than in controls. The odds ratios for SVT were 6.1 (95% confidence interval [CI], 2.6 to 14.2) in patients with the G1691A factor V mutation, 4.3 (95% CI, 1.5 to 12.6) in those with the G20210A prothrombin mutation, and 12.9 (95% CI, 3.6 to 46.2) in those with deficiencies of the naturally occurring inhibitors of coagulation taken together. Risks did not substantially change when the analysis was restricted to 43 patients who had SVT as their only thrombotic manifestation, being 4.3 (95% CI, 1.5 to 12.3) in patients with factor V mutation, and 3.6 (95% CI, 1.0 to 13.1) in those with the prothrombin mutation. Among the circumstantial risk factors investigated (surgery, trauma, prolonged immobilization, oral contraceptives and pregnancy or puerperium), pregnancy or puerperium was the most frequently associated with SVT, being present in 38% of women. Our findings indicate that inherited thrombophilic states are associated with an increased risk for SVT. Hence, a laboratory search of these alterations is recommended in patients with SVT, because it allows the identification of patients at high risk of DVT in whom antithrombotic prophylaxis is particularly warranted.

Adolescent↗
PubMed1999

[Hormone evaluation in brain death].

BACKGROUND: In this study, the level and the variation of a number of hormone and metabolic parameters during brain death treatment in potential organ donors have been monitored. METHODS: Thirty-nine consecutive brain-dead patients were enrolled in 3 Intensive Care Units of Regional Hospitals of the North of Italy. All patients were potential organ donors and free from diseases before the accident leading to death. The levels of ADH, ACTH, TSH, prolactin, cortisol, aldosterone, FT3, FT4, renin, serum lactate and plasma osmolality were measured immediately after the diagnosis of brain death (T0), certified following the Italian law of December 29, 1993, n. 578, and after 6 hours (T6). RESULTS: Hormone levels were normal in the majority of subjects, and there was no significant variation during the 6 hours of the observation period. No correlation was found between the hormone levels considered and the metabolic parameters; ADH levels were not correlated with plasma osmolality. FT3 levels were below the normal range in the majority of subjects, but were not associated with a higher lactate level, which is used as a marker of a shift toward tissue anaerobic metabolism. CONCLUSIONS: In conclusion, triiodothyronine administration to improve metabolic order and thus the function of organs for transplantation is not justified in brain-dead patients.

Adolescent↗
PubMed1998

Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families.

Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first- and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95% confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95% CI, 2.9 to 18.4) or protein S deficiency (8.5, 95% CI, 3. 5 to 20.8), and factor V Leiden (2.2, 95% CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95% CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95% CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90% in antithrombin, 88% in protein C, 100% in protein S deficiency, and 57% in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43%). There was a predisposing factor at the time of venous thromboembolism in approximately 50% of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.

Adolescent↗
PubMed1998

High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives.

BACKGROUND: Idiopathic cerebral-vein thrombosis can cause serious neurologic disability. We evaluated risk factors for this disorder, including genetic risk factors (mutations in the genes encoding factor V and prothrombin) and nongenetic risk factors (such as the use of oral contraceptive agents). We compared the prevalence of these risk factors in 40 patients with cerebral-vein thrombosis, 80 patients with deep-vein thrombosis of the lower extremities, and 120 healthy controls. The G1691A mutation in the factor V gene and the G20210A prothrombin-gene mutation, which are established genetic risk factors for venous thrombosis, were studied. We also assessed the use of oral contraceptives and other risk factors for thrombosis. RESULTS: The prevalence of the prothrombin-gene mutation was higher in patients with cerebral-vein thrombosis (20 percent) than in healthy controls (3 percent; odds ratio, 10.2; 95 percent confidence interval, 2.3 to 31.0) and was similar to that in patients with deep-vein thrombosis (18 percent). Similar results were obtained for the mutation in the factor V gene. The use of oral contraceptives was more frequent among women with cerebral-vein thrombosis (96 percent) than among controls (32 percent; odds ratio, 22.1; 95 percent confidence interval, 5.9 to 84.2) and among those with deep-vein thrombosis (61 percent; odds ratio, 4.4; 95 percent confidence interval, 1.1 to 17.8). For women who were taking oral contraceptives and who also had the prothrombin-gene mutation (seven patients with cerebral-vein thrombosis but only one control), the odds ratio for cerebral-vein thrombosis rose to 149.3 (95 percent confidence interval, 31.0 to 711.0). CONCLUSIONS: Mutations in the prothrombin gene and the factor V gene are associated with cerebral-vein thrombosis. The use of oral contraceptives is also strongly and independently associated with the disorder. The presence of both the prothrombin-gene mutation and oral-contraceptive use raises the risk of cerebral-vein thrombosis further.

Adolescent↗
PubMed1998

A prospective multicenter study of hepatocellular carcinoma in italian hemophiliacs with chronic hepatitis C. The Study Group of the Association of Italian Hemophilia Centers.

To assess the risk factors, natural history, and eligibility for curative treatment of early-detected hepatocellular carcinoma (HCC), 385 hemophiliacs who were treated with blood or plasma derivates for at least 10 years and had persistently elevated aminotransferase values underwent an annual screening with an abdominal ultrasound examination and measurement of the serum alpha-fetoprotein (AFP) level. Of these, 355 had serum antibody to hepatitis C virus (anti-HCV), 29 had anti-HCV and hepatitis B surface antigen (HBsAg), and one had HBsAg alone; 141 had serum antibody to human immunodeficiency virus (anti-HIV). During 48 months of follow-up study, six patients developed HCC. All HCC patients had a HCV-related cirrhosis and had been exposed to HCV risk at a median age of 40 years. All patients had a multicentric tumor, which was not eligible for curative treatment. Univariate analysis showed age, cirrhosis, and baseline AFP levels to be significantly associated with an increased risk of HCC. By multivariate analysis, the risk of HCC was infinite in patients with cirrhosis, 31.0 for those with baseline AFP higher than 11 ng/mL, and 17.9 for those more than 45 years of age. In conclusion, the risk of cancer was greater for patients infected later in life, particularly those with cirrhosis and high AFP. Annual screening of hemophiliacs with ultrasound and AFP fails to identify potentially curable tumors because the diagnosis is made at a late stage of the disease.

Adolescent↗
PubMed1998

Lung cancer risk and CYP1A1 genotype in African Americans.

The role of CYP1A1 genotype in lung cancer risk was assessed in African Americans through a case control study. The complete CYP1A1 genotype, including the frequency of all three polymorphisms (Msp1 [CYP1A1*2], exon 7 [CYP1A1*3] and African American specific [CYP1A1*4]) was determined by PCR on 307 controls and 105 cases of lung cancer among African Americans. We have confirmed our earlier observation of a significant increased risk (odds ratio = 2.8, 95% CI = 1.3-6.5) for lung adenocarcinoma among people with the *4 polymorphism, although we did not observe any association of this polymorphism with overall lung cancer risk. As previously reported, we found that lung adenocarcinoma patients with the *4 RFLP smoked significantly less than patients without this polymorphism, suggesting an important role in cancer risk of low exposure levels to cigarette smoke in subjects carrying susceptibility polymorphisms. There was no association with the other two polymorphisms and lung cancer in this population. When we examined lung cancer risk as a function of composite genotype, taking into account all three polymorphisms simultaneously in each subject, our preliminary data suggested an association of one rare genotype (homozygous Msp1, heterozygous exon 7 or *2/*2*3) with overall lung cancer risk (OR = 8.4, 95% CI = 1.6-43.2).

Adenocarcinoma↗
PubMed1998

Models of interaction between metabolic genes and environmental exposure in cancer susceptibility.

Polymorphic metabolic genes that confer enhanced genetic susceptibility to the carcinogenic effects of certain environmental carcinogens act according to a type 2 interaction between genetic and environmental risk factors. This type of interaction, for which the gene has no effect on disease outcome by itself but only modifies the risk associated with exposure, must be treated differently from other types of gene-environment interaction. We present a method to analyze different dose effects often seen in studies involving these genes. We define a low exposure-gene effect, when a greater degree of gene environment interaction appears at lower doses of exposure (the interaction follows an inverse dose function), and a converse high exposure-gene effect, when the interaction increases as a function of dose. Using a standard logistic regression model, we define a new term, alpha, that can be determined asa function of exposure dose in order to analyze epidemiological studies for the type of exposure-gene effect. These models are illustrated by the use of hypothetical case-control data as well as examples from the literature.

Algorithms↗
PubMed1998

Cadaver kidney allocation in the north Italy transplant program on the eve of the new millennium.

The identification of parameters impacting on cadaver kidney graft outcome is of paramount importance to ensure proper organ allocation, a process that must take into account ethical, biological, social and administrative factors. This is particularly critical in countries where organ procurement is largely insufficient. In the present chapter we report the results of studies carried out to determine the impact of 17 factors on graft survival and function at 4 years posttransplant in 2,917 recipients transplanted from January 1990-September 1997 in the North Italy Transplant program (NITp). Patient and graft survival rates at 4 years (+/- SEM) were 93.5 +/- 0.5% and 81.4 +/- 0.8%, respectively. Excellent graft function at 4 years was shown by 69.8% of recipients. Younger donor age, absence of pretransplant transfusions, patient dialysis center in the NITp area and level of HLA match showed a statistically significant positive association with graft survival. Younger donor age and male donor gender showed a statistically significant association with excellent graft function at 4 years. These global outcomes were confirmed when the analysis was limited to the subset of the 2,617 adult recipients and to the subset of 1,211 cases for whom both donor and recipient HLA-DRB1 types were available before transplant. The results were used to develop a computer-assisted, refined version of the NITp adult kidney allocation algorithm that was named NITK3. A preliminary evaluation of 472 transplants allocated in 12 months with NITK3 compared with 459 transplants allocated in the preceding 12 months according to the previous algorithm (NITK2) showed a significantly higher proportion of recipients who had been on the waiting list for more than 3 years (33.1% vs 21.1%). The use of NITK3 was also associated with a significantly increased ability to transplant alloimmunized patients (17.7% vs 9.5% with NITK2) and recipients with 0-1 HLA mismatches (21.2% vs 13.5% with NITK2). Differences in 6-month graft survival rates and in the percentage of patients with excellent function at 6 months were not statistically significant in recipients transplanted with NITK3 versus NITK2. Survival rates were 96.9% and 92.4%, respectively. Percentages of patients with excellent renal function were 68.3% and 70.5%, respectively. These preliminary data suggest that NITK3 improves HLA match and reduces the number of patients on the waiting list for 3 or more years without determining significant modifications of 6-month graft survival and function. Moreover, it facilitates the achievement of a fair local balance between organs retrieved and transplanted, the compliance of operators with objective allocation rules and the documentation of the whole allocation process.

Adolescent↗
PubMed1998

Serum autoantibodies recognizing 5-hydroxymethyl-2'-deoxyuridine, an oxidized DNA base, as biomarkers of cancer risk in women.

Human sera contain anti-5-hydroxymethyl-2'-deoxyuridine (HMdU; an oxidized thymidine) autoantibodies (aAbs), which are significantly higher in chronic inflammatory diseases. The intent of this study was to establish whether anti-HMdU aAbs can serve as predictors of breast and colorectal cancer risk. Sera of 169 women were analyzed by ELISA. Women healthy at blood donation but who were diagnosed 0.5-6 years later with breast or colorectal cancer exhibited significantly increased anti-HMdU aAbs over the age-matched controls (P = 0.028 and P < 0.001, respectively). Subjects diagnosed with rectal cancer had the highest levels of anti-HMdU aAbs (44.80 +/- 11.50; n = 6) in comparison to colon (29.03 +/- 2.49; n = 33) and breast (35.86 +/- 8.55; n = 9) cancers. Individuals with benign breast disease also had elevated anti-HMdU aAb (35.12 +/- 8.77; n = 10), with a borderline statistical significance (P = 0.095), whereas those with benign gastrointestinal tract diseases had those titers (30.95 +/- 3.64; n = 8) significantly increased (P < 0.02). Anti-HMdU aAb levels in subjects with a family history of any cancer (23.57 +/- 2.86; n = 55) did not significantly differ from those of the controls (19.41 +/- 2.90; n = 48), but women with a family history of breast cancer (two primary relatives or one with a bilateral disease) showed increased levels (34.48 +/- 8.16; n = 8; P = 0.024). Ps for linear trend of age-adjusted odds ratios were 0.049 for breast and < 0.001 for colorectal cancers. Anti-HMdU aAb titers showed a remarkable stability over a period of 6 years, with a low (14%) intraindividual variance. Thus, elevated anti-HMdU aAb titers may be an early signal of cancer risk, because they were significantly increased in otherwise healthy women who had a family history of breast cancer; in those who had benign breast disease or benign gastrointestinal tract diseases; and, most importantly, in those who at 0.5-6 years after the initial blood donation developed breast or colorectal cancer.

Adult↗