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Biomedical subjects

A Estellés

Publications and source records attributed to A Estellés.

At least 19 recordsLinked to original sources
PubMed2003

Expression of several components of the plasminogen activator and matrix metalloproteinase systems in endometriosis.

BACKGROUND: Endometriosis is considered a benign disease that has the ability to invade normal tissue. As in neoplastic growth, local extracellular proteolysis may take place. The aim of this study is to analyse several components of the plasminogen activator (PA) pathway and the matrix metalloproteinase (MMP) system in endometriotic tissue, endometrium and peritoneal fluid from women with and without endometriosis (controls). METHODS AND RESULTS: Thirty-nine women with endometriosis and 35 controls were studied. In eutopic endometrium of women with endometriosis, the antigenic levels of urokinase-type PA (uPA) and MMP-3 were elevated when compared with endometrium from controls. Ovarian endometriotic tissues had higher antigenic levels of PA inhibitor type 1 (PAI-1) and tissue inhibitor of metalloproteinases type 1 (TIMP-1) than endometrium. The peritoneal fluid from women with endometriosis showed a significant increase in uPA levels compared with controls. CONCLUSIONS: The increase in antigenic levels of uPA and MMP-3 in endometrium of women with endometriosis might contribute to the invasive potential of endometrial cells. Once the ovarian endometriotic cyst is developed, an increase in PAI-1 and TIMP-1 is detected and significant proteolytic activity is no longer observed. This increase in inhibitors and decrease in proteolytic activity could explain the frequent clinical finding of isolated endometriotic cyst without invasion of the surrounding ovarian tissue.

Adult↗
PubMed2002

Changes in molecular forms of prostate-specific antigen during treatment with finasteride.

OBJECTIVE: To study the influence of finasteride treatment on the molecular forms of prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Total PSA, free PSA and PSA complexed to alpha1-antichymotrypsin (PSA-alpha1ACT) were measured in plasma and serum from 40 men with BPH and a total PSA of < 20 ng/mL, using in-house and commercial immunoassays, before and during treatment with finasteride (30 men) or placebo (10 men). RESULTS: The baseline values were not significantly different between the groups, with mean (sd) total plasma PSA levels of 3.6 (4.3) and 4.8 (5.9) ng/mL in the finasteride and placebo groups, respectively. Finasteride, but not placebo, induced a significant reduction in total PSA, free PSA and PSA-alpha1ACT levels in plasma and serum (P < 0.001). However, complexed-to-total (c/t) and free-to-total (f/t) PSA ratios remained constant in both groups, both in plasma and serum, during the follow-up. CONCLUSION: The decrease in total PSA after finasteride treatment results from a proportional reduction in its two major molecular forms, free PSA and PSA-alpha1ACT, which explains why the c/t and f/tPSA ratios do not change significantly despite treatment. This suggests that routine analysis of molecular forms of PSA could improve the utility of the change in total PSA associated with finasteride for the early diagnosis of prostate cancer. It also suggests that any subsequent change in both ratios, particularly an increase in c/tPSA or a decrease in f/tPSA ratio, could be considered an early sign of neoplastic degeneration rather than a therapeutic consequence.

Aged↗
PubMed2001

[PSA:alpha 1-antichymotrypsin ratio/total PSA in the diagnosis of prostatic cancer in the range of total PSA from 4 to 10 ng/ml].

OBJECTIVE: To evaluate the usefulness of the ratio PSA:alpha-1-antichymotrypsin/total PSA (C/T) in the diagnosis of prostate cancer in the range of total PSA between 4 and 10 ng/mL. MATERIAL AND METHODS: By using home-made ELISAs we have determined plasmatic concentrations of total PSA and complex PSA:alpha-1-ACT in 300 patients with total PSA between 4-10 ng/mL. All samples were obtained before any manipulation that could interfere the PSA levels. RESULTS: By prostatic biopsy 85 patients (28.3%) were diagnosed of prostate cancer (CaP) and 215 (71.6%) of benign prostatic hyperplasia (BPH). The mean values of the complex PSA:alpha-1-ACT (4.2 ng/mL in the BPH patients vs 5.0 ng/mL in the CaP patients) and of the C/T ratio (0.70 vs 0.82, respectively) showed significant differences between both groups (p = < 0.0001). The total PSA did not show differences (6.1 ng/mL vs 6.0 ng/mL; p = 0.79). From all three parameter evaluated, the ratio C/T had the biggest area under the ROC (0.884) and statistically significant differences in comparison with total PSA (0.490; p = < 0.001) and the complex PSA:alpha-1-ACT (0.696: p = < 0.001). Therefore, by using a ratio C/T > 0.62 to decide the performance of a biopsy, 27% of the patients with BPH could have avoided this procedure with a 100% sensitivity. Increasing the ratio to 0.68 the specificity is 47% and the sensitivity is 95.2%. Rectal examination did not have influence on the cut-off, sensitivity, specificity and area under the ROC of the ratio C/T. CONCLUSIONS: Our results confirm that the ratio C/T improve the diagnostic capacity of the total PSA between 4-10 ng/ml. Moreover, the rectal examination does not influence the selection of ratio C/T cut-off suggestives of CaP neither the diagnostic efficacy.

Aged↗
PubMed2001

[Factors affecting the PSA:alpha 1 antichymotrypsin/total PSA ratio].

OBJECTIVES: To evaluate the influence of several factors, including age, prostate volume, total PSA (PSA-T), clinical stage and Gleason on the PSA:alpha 1ACT/PSA-T (C/T) ratio. MATERIAL AND METHODS: Using in-house assays, we measured plasma levels of PSA-T and PSA:alpha 1ACT complex in 622 patients with benign prostate hyperplasia (BPH) (455 with hystological confirmation and 167 with clinical evidence of absence of malignance) and in 255 patients with prostate cancer (CaP), and determined the correlation between different parameters. RESULTS: In BPH patients, PSA-T and PSA:alpha 1ACT significantly increased with age. There was a positive correlation between age and PSA-T (r = 0.161, p < 0.0001) and PSA:alpha 1ACT (r = 0.141, p = 0.001). In contrast, the C/T ratio remained constant and below 70% in all decades. Similar results were obtained in CaP patients. In BPH patients, there was a positive correlation between prostate volume and PSA-T and PSA:alpha 1ACT, but not with the C/T ratio. In CaP patients, however, there was a negative correlation between prostate volume and the C/T ratio. An excellent correlation was found between PSA-T and PSA:alpha 1ACT, and a good correlation between PSA-T and the C/T ratio and between PSA:alpha 1ACT and C/T ratio. A multiple regression analysis showed that, in HBP and CaP patients, PSA-T and PSA:alpha 1ACT complex were the only parameters that significantly and independently influenced the C/T ratio. CONCLUSIONS: The C/T ratio is independent of age, prostate volume, Gleason and clinical stage. Therefore, these factors need not to be considered when using the C/T ratio.

Adult↗
PubMed2001

Factor V Leiden and prothrombin G20210A in relation to arterial and/or vein rethrombosis: two cases.

The factor V Leiden (FV Leiden) and prothrombin G20210A mutations, are the most common established genetic risk factors for deep vein thrombosis (DVT). However, the relationship between these mutations and arterial thrombotic syndromes (coronary heart disease, myocardial infarction, stroke) has not been established. Some studies have suggested a relationship between them, but other authors have considered it unlikely that these anomalies are a major risk factor for arterial thrombosis. From the clinical point of view, a question arises concerning the risk of repeated thrombosis in patients carrying one of these two mutations. The question is whether the recurrence is attributable to the mutations or to the presence of additional circumstantial risk factors. As the risk of repeated thrombosis varies considerably from one patient to another, decisions about long-term treatment require weighing the persistence of risk factors for vascular disease (venous and arterial), especially in selected cases such as young patients or patients with thrombosis of unusual localization.

3' Untranslated Regions↗
PubMed2001

Fibrinolysis and lipoprotein(a) in women with coronary artery disease. Influence of hormone replacement therapy.

BACKGROUND AND OBJECTIVES: The incidence of coronary artery disease (CAD) is higher in post-menopausal than in pre-menopausal women. Epidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in post-menopausal women. HRT could modify the cardiovascular risk via several mechanisms, including modifications in the fibrinolytic system and lipoprotein (a) levels. Our study was aimed at investigating some of these modifications. DESIGN AND METHODS: In the cross-sectional part of the study we evaluated several components of the fibrinolytic system, coagulation inhibitors and lipid profile in premenopausal (n=15) and post-menopausal women (n=64) with CAD and compared these parameters with those of healthy pre-menopausal (n=31) and post-menopausal women (n=88). The prospective part of the study analyzed the effect of HRT with transdermal estrogen with or without progestogen in post-menopausal women with CAD. RESULTS: Pre- and postmenopausal women with CAD showed significant lower fibrinolytic activity and higher plasminogen activator inhibitor type 1 (PAI-1) levels than their control groups. Lp(a) levels were higher in premenopausal women with CAD than in healthy premenopausal women. In post-menopausal women with CAD, HRT induced a significant decrease in PAI-1 and Lp(a) levels. No significant differences were observed in any parameter studied between the groups treated with transdermal estrogen with and without progestogen. INTERPRETATION AND CONCLUSIONS: CAD is associated with a decrease in fibrinolytic activity, possibly due to an increase in PAI-1 levels. An increase in fibrinolytic activity and a decrease in PAI-1 and Lp(a) levels were observed in CAD women receiving transdermal HRT and these changes may have a favorable impact on the risk of new cardiovascular events in post-menopausal CAD women.

Administration, Cutaneous↗
PubMed2001

Plasma PAI-1 levels in obese children--effect of weight loss and influence of PAI-1 promoter 4G/5G genotype.

An association between an increase in plasminogen activator inhibitor type 1 (PAI-1) and obesity, and also between elevated levels of PAI-1 and the presence of PAI-1 promoter 4G allele has been described in adults and can contribute to increased risk of cardiovascular disease. It has also been suggested that in adults a decrease in adiposity has beneficial effects on the haemostatic system. However, less information is available regarding adiposity and fibrinolysis in children. The aim of the present study is to evaluate the effect of weight loss and the influence of the PAI-1 promoter 4G/5G genotype on the fibrinolytic system and lipid parameters in obese children. The clinical groups included 102 obese children and 105 controls of similar age and sex distribution. A significant decrease in fibrinolytic activity due to a significant increase in PAI-1 antigen and activity levels was observed in the obese children in comparison with the control group. In obese children, no significant differences in PAI-1 levels between the PAI-1 4G/5G genotypes were obtained. A significant correlation was observed between PAI-1 antigenic and functional levels and body mass index (BMI), as well as between PAI-1 levels and both triglyceride and insulin levels. No correlation between PAI-1 levels and either cholesterol or glucose levels was observed. After a three-month period of treatment to reduce weight, an increase in fibrinolytic activity due to a decrease in PAI- levels was observed in the obese children who had reduced their BMI in comparison with the group of obese children who did not show a decrease in their BMI. No significant differences between the two groups with respect to the variations in tissue type plasminogen activator and fibrinogen levels were obtained after three months of intervention to reduce weight. A significant correlation was observed between variations in BMI and variations in PAI-1 levels, and a significant inverse correlation was also observed between previous PAI-1 levels and variation in PAI-1 levels. Therefore, the largest decrease in PAI-1 levels was observed in the obese children with the highest previous PAI-1 levels. In conclusion, a decrease in BMI in obese children shows a favourable effect on the fibrinolytic system due to a decrease in PAI-1 levels. However, no influence of 4G/5G genotype on PAI-1 levels was observed.

Adolescent↗
PubMed2001

Low level of circulating activated protein C is a risk factor for venous thromboembolism.

The levels of circulating activated protein C (APC) reflect in vivo protein C activation. The aim of this study was to determine whether a low APC level is an independent risk factor for venous thromboembolism (VTE). We measured APC in 160 patients with a history of VTE and without recognized thrombophilic defects, and in 199 healthy individuals. The mean (+/- SD) APC level was lower in patients (0.99 +/- 0.44 ng/ml) than in controls (1.19 +/- 0.41 ng/ml) (p < 0.0001), and showed a different distribution in the two groups. Thirty-eight patients (23.7%) had APC levels below the 5th percentile of the control group (<0.69 ng/ml) and 57 patients (35.6%) had APC levels below the 10th percentile (<0.77 ng/ml). APC levels <0.69 ng/ml increased the risk of a single or recurrent episode of VTE 4.2-fold (95% confidence interval, 2.0-9.0) or 6.9-fold (2.6-17.9). respectively, and APC levels <0.77 ng/ml increased these risks 3.4-fold (1.9-6.2) or 5.1-fold (2.3-11.2), respectively, compared with controls. Familial studies revealed that in some cases the low APC phenotype seems to be hereditary. We conclude that a low level of circulating APC in individuals without any of the most recognized thrombophilic defects is a prevalent, independent risk factor for VTE, and that it predisposes to recurrent VTE.

Adult↗
PubMed2000

PAI-1 promoter 4G/5G genotype as an additional risk factor for venous thrombosis in subjects with genetic thrombophilic defects.

Impaired fibrinolysis as a result of increased plasminogen activator inhibitor-1 (PAI-1) levels in plasma is a common finding in patients with deep vein thrombosis (DVT). A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to influence the levels of PAI-1. The 4G allele was found to be associated with higher plasma PAI-1 activity (act), but contradictory results on the incidence of the 4G allele in DVT patients have been reported. The aim of this study was to analyse whether the PAI-1 promoter 4G/5G genotype increases the risk of venous thrombosis in subjects with thrombophilic defects, and to determine the distribution of the PAI-1 4G/5G genotype and its relation to plasma PAI-1 levels in 190 unrelated patients with DVT in comparison with a control group of 152 healthy subjects. No differences between the 4G/5G allele distribution in the DVT group (0.43/0.57) and in the control group (0.42/0.58) were observed. However, the presence of the 4G allele significantly increased the risk of thrombosis in patients with other thrombophilic defects. Significantly higher PAI-1 levels were observed in DVT patients than in the controls. Our results also showed significant differences in the plasma levels of PAI-1 antigen (ag) and PAI-1 act among the 4G/5G genotypes in DVT patients. A multivariate analysis revealed that, in the DVT group, PAI-1 ag levels were influenced by the 4G allele dosage, triglyceride levels and body mass index (BMI). The influence of the 4G allele dosage on PAI-1 levels was independent of the triglyceride levels and BMI. In the control group, no significant correlation between PAI-1 levels and 4G allele dosage was observed. In conclusion, the PAI-1 promoter polymorphism was found to have an influence on PAI-1 levels in DVT patients and on the risk of venous thrombosis in subjects with other genetic thrombophilic defects.

Adult↗
PubMed2000

Prostate-specific antigen complexed to alpha(1)-antichymotrypsin in the early detection of prostate cancer.

OBJECTIVES: To study the usefulness of the complexed-to-total (C:T) prostate-specific antigen (PSA) ratio in the early detection of prostate cancer in patients with a total PSA value <4.0 ng/ml. PATIENTS AND METHODS: Total PSA and PSA complexed to alpha(1)-antichymotrypsin were measured in plasma from 193 men with benign prostatic hyperplasia (BPH) and 34 with prostate cancer. The diagnosis was confirmed in 28 BPH and 16 prostate cancer patients by biopsy and in 165 BPH and 18 prostate cancer patients by histological study following transurethral prostatectomy or open prostatectomy. RESULTS: The area under the receiver operating characteristic (ROC) curve was significantly greater for the C:T PSA ratio (0.908) than for total PSA (0.692) (p<0.001). Using a cut-off point of 0.83 for the C:T PSA ratio and regardless of the digital rectal examination (DRE) finding, 20 of the 34 prostate cancer patients would have been given a correct diagnosis (59% sensitivity) and in only 8 of the 193 BPH patients would a biopsy have been necessary (96% specificity). With a cut-off of 0.79, the sensitivity increased to 85% with a specificity of 92%. When the analysis was restricted to the 44 patients with abnormal DRE, the area under the ROC curve for the C:T PSA ratio was 0.919, and a cut-off point of 0. 78 gave a sensitivity of 87% and a specificity of 93%. Using a cut-off of 0.63, all prostate cancers were detected (100% sensitivity) and 54% of the negative biopsies would have been eliminated. For the 183 patients diagnosed following surgery, a cut-off of 0.82 gave a sensitivity of 72% and a specificity of 94%. CONCLUSION: Our results show that the C:T PSA ratio significantly improves the clinical utility of the PSA assay for detecting prostate cancer in patients with total PSA < 4 ng/ml, increasing the sensitivity without significantly increasing the number of biopsies.

Aged↗
PubMed2000

Congenital and acquired thrombotic risk factors in women using oral contraceptives: clinical aspects.

We describe the thrombophilic and clinical characteristics of a group of patients who suffered venous thrombosis (VT) (n = 36) and ischemic stroke (n = 8) while taking oral contraceptives (OC). Our purpose is to ascertain whether there are differences between users of second and third generation progestogen and to investigate the influence of concurrent congenital and acquired risk factors (other than OC) on the onset of the thrombosis. The group of patients included 36 women with VT and eight with ischemic stroke. The patients' recognized predisposing factors were recorded. We also considered age, length of time on OC, types of OC, rethrombosis, family history of VT, and the presence of thrombophilic genetic defects. In the group of patients with VT, 54% were treated with second generation OC (n = 23), and 30% (n = 11) were treated with third generation OC. We found no significant statistical differences with respect to age and length of time on OC between the two types of OC. The prevalence of genetic defects in these patients--factor V (FV) Leiden, prothrombin G20210A mutation and protein S deficiency--was 19% (n = 7), 17% (n = 6), and 8% (n = 3) respectively. We observed the shortest time lapse between initiating OC and the first thrombotic event in carriers of FV Leiden and in patients with combined defects, but the differences were not significant. In patients with ischemic stroke, 50% were treated with second generation OC and 50% were treated with third generation OC. Prothrombin G20210A mutation was detected in two patients. In both patients,the stroke occurred earlier than in the rest of the patients, but these differences were not statistically significant. With respect to preventing thrombotic events in these patients, our data suggest that OC therapy should be avoided in patients with a previous history of thrombosis and in patients with an evident thrombotic tendency in the family. In patients in whom the family history of thrombosis is not very evident, it would be recommended to screen for FV Leiden, prothrombin G20210A mutation, and protein S, and to rule out OC if the patient does in fact have one of these risk factors. Moreover, if a patient develops a thrombotic complication while taking OC, an evaluation to search for a thrombophilic defect is warranted, and at the same time, alternative methods of contraception should be considered.

Adolescent↗
PubMed2000

Portal vein thrombosis associated to prothrombin G20210A mutation and protein C deficiency.

We describe a patient with left branch portal vein thrombosis involving two thrombophilic alterations, the prothrombin G20210A mutation and protein C deficiency. In spite of not being under anticoagulant treatment, the thrombus in the portal vein underwent complete and spontaneous lysis. No other risk factors were detected and no family history related to thrombosis was found.

Adenine↗
PubMed2000

Intracardiac thrombosis in a case of Behcet's disease associated with the prothrombin 20210G-A mutation.

Thrombosis occurs in 20 to 30% of patients with Behçet's disease (BD), but the precise pathogenic mechanism underlying the thrombotic tendency in these patients is not well known. Venous thromboses are commonly located in the lower extremities, but right intracardiac thrombi are extremely rare. We report for the first time on a young patient with BD associated the 20210G-A prothrombin gene mutation and right intracardiac thrombosis. We suggest that the association of BD with this newly recognized prothrombotic genetic mutation may have contributed to the development of the thrombotic event in this patient.

Adolescent↗
PubMed2000

Risk of venous thrombosis in carriers of the prothrombin G20210A variant and factor V Leiden and their interaction with oral contraceptives.

BACKGROUND AND OBJECTIVES: The prothrombin G20210A mutation and factor V Leiden have been found to be associated with an increased risk of venous thrombosis, but the reported prevalences of the prothrombin gene variant both in the normal population and in patients with deep venous thrombosis (DVT) vary greatly in the literature. Moreover, the influence of oral contraceptives (OC) on thrombotic events in patients with the prothrombin G20210A variant has not been well established. In this study we evaluate both circumstances. DESIGN AND METHODS: A case-control study was run on 229 patients with DVT and 246 healthy controls. The patients' history of thrombosis and acquired thrombotic risk factors, especially OC, were recorded. Prothrombin G20210A mutation, factor V Leiden, antithrombin, heparin II cofactor, plasminogen and proteins C and S were evaluated. RESULTS: Seven and a half percent of the patients and 2.9% of the controls were carriers of the prothrombin mutation, while 12.2% of the patients and 1.6% of the controls had factor V Leiden. Among the 229 DVT patients there were 130 patients with clinically suspected thrombophilia (first thrombotic event occurring before the age of 45 years or positive family history of thrombosis or recurrent venous thrombosis). Ten percent of these 130 patients were carriers of the prothrombin G20210A mutation and 18.5% had the factor V Leiden mutation. The odds ratios (OR) for DVT risk were: 2.4 (95% CI, 1.0-6.3) for the total DVT patients and 5.2 (95% CI, 1.4-19.5) for the patients with clinically suspected thrombophilia with the prothrombin mutation. The risk of thrombosis was 6.9 (95% CI, 2.3-20.6) for the DVT patients and 14.3 (95% CI, 3.3-64.6) for the patients with clinically suspected thrombophilia with factor V Leiden. Fifty-five percent of the patients with combined congenital defects (prothrombin mutation G20210A plus another congenital defect) had recurrent thrombosis. In women receiving OC the risk of DVT was 3.5 (95% CI, 1.5-8.2) that of the patients not receiving OC. When women with combined defects were also taking OC, the risk of thrombosis increased significantly. INTERPRETATION AND CONCLUSIONS: The prevalence of the prothrombin G20210A mutation in the healthy population in our study is similar to that observed in other southern European countries. The prothrombin G20210A mutation does not by itself seem to be a high thrombotic risk factor. However, when it is present together with other thrombotic risk factors, the predicted risk of thrombotic events increases. The use of OC by women with the prothrombin G20210A variant or FV Leiden, either alone or combined with other thrombotic risk factors, was associated with a significant increase in the risk of venous thrombosis.

Adult↗