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Biomedical subjects

J Aznar

Publications and source records attributed to J Aznar.

At least 19 recordsLinked to original sources
PubMed1999

Factor V Leiden and antibodies against phospholipids and protein S in a young woman with recurrent thromboses and abortion.

We describe the case of a 39-year-old woman who suffered two iliofemoral venous thromboses, a cerebral ischemic infarct and recurrent fetal loss. Initial studies showed high levels of antiphospholipid antibodies (APAs) and a moderate thrombocytopenia. After her second miscarriage, laboratory diagnosis revealed that the woman was heterozygous for the factor V Leiden mutation and had a functional protein S deficiency as well as anti-protein S and anti-beta 2-glycoprotein I antibodies. The impairment of the protein C pathway at various points could well explain the recurrent thromboses in the patient and supports the role of a disturbed protein C system in the pathophysiology of thrombosis in patients with APAs.

Abortion, Habitual↗
PubMed1998

Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality: the effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity.

BACKGROUND: Aspirin (acetylsalicylic acid, ASA) is widely used for secondary prevention of ischemic vascular events, although its protection only occurs in 25% of patients. We previously demonstrated that platelet reactivity is enhanced by a prothrombotic effect of erythrocytes in a thromboxane-independent manner. This diminishes the antithrombotic therapeutic potential of ASA. Recent data from our laboratory indicate that the prothrombotic effect of erythrocytes also contains an ASA-sensitive component. In accordance with this observation, intermittent treatment with high-dose ASA reduced the prothrombotic effects of erythrocytes ex vivo in healthy volunteers. In the present study, the effects of platelet-erythrocyte interactions were evaluated ex vivo in 82 patients with vascular disease: 62 patients with ischemic heart disease treated with 200 mg ASA/d and 20 patients with ischemic stroke treated with 300 mg ASA/d. METHODS AND RESULTS: Platelet activation (release reaction) and platelet recruitment (fluid-phase proaggregatory activity of cell-free releasates from activated platelets) were assessed after collagen stimulation (1 microg/mL) of platelets, platelet-erythrocyte mixtures, or whole blood. Platelet thromboxane A2 synthesis was inhibited by >94% by ASA administration in all patients. Importantly, platelet recruitment followed one of three distinct patterns. In group A (n=32; 39%), platelet recruitment was blocked by ASA both in the presence and absence of erythrocytes. In group B (n=37; 45%), recruitment was abolished when platelets were evaluated alone but continued in the presence of erythrocytes, indicating a suboptimal effect of ASA on erythrocytes of this patient group. In group C (n= 13; 16%), detectable recruitment in stimulated platelets alone persisted and was markedly enhanced by the presence of erythrocytes. CONCLUSIONS: In two thirds of a group of patients with vascular disease, 200 to 300 mg ASA was insufficient to block platelet reactivity in the presence of erythrocytes despite abolishing thromboxane A2 synthesis. Platelet activation in the presence of erythrocytes can induce the release reaction and generate biologically active products that recruit additional platelets into a developing thrombus. Insufficient blockade of this proaggregatory property of erythrocytes can lead to development of additional ischemic complications.

Adult↗
PubMed1998

Diagnostic value of cytokeratin fragment 19 (CYFRA 21-1) in bronchoalveolar lavage fluid in lung cancer.

The aim of this study was to evaluate the diagnostic value of a new tumour marker, cytokeratin fragment 19 (CYFRA 21-1), in bronchoalveolar lavage fluid (BALF) for the diagnosis of lung cancer. The cross-sectional study included 36 patients with lung cancer, 19 with benign lung diseases and 13 control subjects. In the group with cancer, BAL was performed in the cancer-involved lung and in the opposite lung. Results in BALF were expressed both as absolute concentrations (ng ml-1) and referred to total protein (TP) (ng mg-1 TP), and results in plasma were expressed in ng ml-1. In BALF, there was no significant different between cancer and control groups. Using the 95th percentile of levels obtained in benign lung disease in BALF (specificity 95%) as the cut-off point, the sensitivity of CYFRA 21-1 was 13%. Positive and negative predictive values (PPV and NPV) at different pretest probabilities, and positive and negative gains were obtained applying a Bayesian analysis. Results showed low positive gains for PPV (maximal increase of 22%) and almost none for NPV (negative gains < 5%). In plasma, CYFRA 21-1 provided a sensitivity of 65%. The combination of BALF and plasma tumour marker levels showed a sensitivity of 69%. Therefore, measurement of CYFRA 21-1 in BALF has poor diagnostic value in lung cancer.

Antigens, Neoplasm↗
PubMed1998

Longitudinal evaluation of the complexed-to-total prostate specific antigen ratio in men with prostate disease. Effect of treatment.

The longitudinal changes in the complexed-to-total prostate specific antigen (PSA) ratio were evaluated in 90 men with benign prostatic hyperplasia (BPH) and 50 men with prostate cancer. The influence of treatment on this ratio was studied in 45 BPH patients and 50 patients with prostate cancer. Using a cut-off of 0.80 for the complexed-to-total PSA ratio, the large majority of prostate cancer patients had a ratio above the cut-off before treatment in serial determinations, whereas most BPH patients had a ratio consistently below that value. However, the few prostate cancer patients who had a ratio < or = 0.80 showed this low ratio in serial determinations, as did BPH patients who had a ratio > or = 0.80. During treatment, the ratio significantly decreased in 43 of the 50 patients with prostate cancer in parallel with the decrease in total PSA, and 34 of the 41 patients that had a pretreatment ratio > 0.80 showed a ratio < or = 0.80 during hormonal therapy. Our results show that neither the physiological changes in total and complexed PSA nor the treatment of BPH patients change the diagnostic efficacy of the complexed-to-total PSA ratio, whereas in prostate cancer patients under hormonal therapy, the ratio decreased in parallel with the decrease in total PSA. This suggests that, apart from improving the diagnostic efficacy of total PSA, the complexed-to-total PSA ratio could also be used to monitor BPH patients for newly developed tumours or to monitor therapy in patients with prostate cancer.

Antineoplastic Agents, Hormonal↗
PubMed1998

Markers of coagulation and platelet activation during percutaneous mitral valvuloplasty.

The effect of percutaneous mitral valvuloplasty (PMV) on markers of coagulation and platelet activation was investigated to assess whether coagulation or platelet activation take place during and after PMV even under conditions of full heparinization. Before PMV, all the hemostatic parameters studied were in the normal range compared with those of a control group. Two hours after PMV the levels of prothrombin fragment F1 and 2 (F1+2) (1.6+/-0.6 nmol/l versus 0.8+/-0.3 nmol/l, P < 0.005), plasma thrombin-antithrombin III (TAT) complexes (5.4+/-3.2 ng/ml versus 2.2+/-0.9 ng/ml) and beta-thromboglobulin (119+/-70 ng/ml versus 42.2+/-41 ng/ml) had increased significantly compared with those measured at basal conditions. Activated partial thromboplastin time was significantly prolonged (152+/-40 s versus 21+/-5 s), reflecting full heparinization. Levels of fibrinogen, F1+2, TAT and beta-thromboglobulin remained increased 72 h after PMV. We conclude that patients with severe, symptomatic mitral stenosis undergoing PMV need a more specific antithrombotic therapy or a more prolonged and perhaps less intensive heparinization.

Adult↗
PubMed1998

Free and complexed prostate specific antigen in the differentiation of benign prostatic hyperplasia and prostate cancer: studies in serum and plasma samples.

PURPOSE: We prospectively evaluated serum and plasma concentrations of total and free prostate specific antigen (PSA), and PSA complexed to alpha1-antichymotrypsin in 170 patients who underwent biopsy, including 59 with prostate cancer and 111 with benign prostatic hyperplasia. We compared the usefulness of the ratios of free-to-total and complexed-to-total PSA for distinguishing between prostate cancer and benign prostatic hyperplasia, and studied the influence of blood clotting on the ratios. MATERIALS AND METHODS: Blood samples were processed to generate serum and citrated plasma. To calculate complexed-to-total and free-to-total PSA we assayed plasma and serum samples for total and complexed PSA using homemade immunoassays, and total and free PSA using the Immulite assay. The 2 total PSA assays were compared using the Tandem-E PSA assay. Receiver operating characteristics curves were constructed for the total population, and for 2 to 20, 4 to 20, 2 to 10 and 4 to 10 ng./ml. total PSA. RESULTS: In all groups complexed-to-total PSA had higher specificity than free-to-total and total PSA, especially at 90 to 100% sensitivity. Generally citrated plasma samples provided higher specificity than serum samples for all sensitivity values. The best performance for complexed-to-total and free-to-total PSA was obtained in the subset of patients in whom total PSA was 2 to 10 ng./ml. CONCLUSIONS: Our results indicate that the complexed-to-total PSA ratio performed better for classifying disease status than the free-to-total PSA ratio in the whole patient population and in the diagnostic gray zone of 2 to 10 ng./ml. In addition, plasma samples should be used to calculate the complexed-to-total and free-to-total PSA ratio.

Aged↗
PubMed1998

Abnormal expression of type 1 plasminogen activator inhibitor and tissue factor in severe preeclampsia.

Preeclampsia is a multisystemic obstetric disease of unknown etiology that is commonly associated with fibrin deposition, occlusive lesions in placental vasculature, and intrauterine fetal growth retardation. We previously reported that type 1 plasminogen activator inhibitor (PAI-1) levels are significantly increased in plasma and placenta from pregnant women with preeclampsia compared to normal pregnant women. In the present report we localize the expression of placental PAI-1 in greater detail and compare it with that of tissue factor (TF), a procoagulant molecule, and vitronectin (Vn), a PAI-1 cofactor. We also examine the expression of two cytokines, tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1), in order to begin to define the underlying mechanisms responsible for the elevated levels of PAI-1 and fibrin deposits observed in placenta from preeclampsia. We demonstrate a significant increase in PAI-1, TF and TNFalpha antigen and PAI-1 and TF mRNA in placentas from preeclamptic patients. PAI-1 mRNA was increased not only in syncytiotrophoblast and infarction areas, but also in fibroblasts and in some endothelial cells of fetal vessels in placentas from preeclamptic patients. However, there was no colocalization between PAI-1, TF, Vn and TNFalpha in placental villi. The elevated TNFalpha in the placenta may induce PAI-1 and TF, and thus promote the thrombotic alterations associated with preeclampsia.

Female↗
PubMed1998

Influence of lipoprotein (a) levels and isoforms on fibrinolytic activity--study in families with high lipoprotein (a) levels.

Increased levels of lipoprotein (a) [Lp(a)] have been considered an independent risk factor for cardiovascular disease, but the mechanism behind this relationship is not completely understood. A high concentration of Lp(a) may interfere with fibrinolysis because of the structural similarity between apo(a) and plasminogen. The aim of the present study was to examine the influence of apo(a) levels and isoforms on fibrinolytic activity in 82 subjects from 24 families in which the Lp(a) levels were > or =30 mg/dl in at least one child and one parent. Several fibrinolytic parameters, including plasmin generation by fibrin-bound tissue plasminogen activator, the lipid profile and apo(a) isoforms were studied. Subjects with high circulating Lp(a) levels (n = 44) had significantly reduced plasmin generation compared with their relatives with normal Lp(a) levels (n = 38). A significant inverse correlation between Lp(a) levels and plasmin generation was observed. The individuals with a combination of high levels of plasma Lp(a) and a major apo(a) isoform < or =580 kD molecular weight show the lowest fibrinolytic activity. A high correlation was found between the levels of apo(a) isoforms in children and the levels of the corresponding parental apo(a) isoforms. We conclude that the antifibrinolytic effect of Lp(a) in subjects with two apo(a) isoforms may depend not only on the total plasma level of Lp(a) but also on the relative concentration of the small apo(a) isoform.

Adolescent↗
PubMed1998

Anaerobic bacteria in men with urethritis.

AIM: Investigation of the urethral flora in men with urethritis, with particular reference to anaerobic bacteria. METHODS: Multiple cultures were performed on three urethral samples from 110 men attending the STD Clinic of the School of Medicine in Seville: 35 with no evidence of urethritis (control group), and 75 with urethritis (17 gonococcal urethritis (GU) and 58 non-gonococcal urethritis (NGU)). In the 58 men with NGU, Chlamydia trachomatis was isolated in 16 (27.5%), Ureaplasma urealyticum in 18 (31%), Trichomonas vaginalis in two (3.4%) and no pathogens were isolated in the remaining 22 (38%) patients. RESULTS: Aerobic flora, mainly Staphylococcus spp., were isolated less frequently (41%) in patients with GU than in the control group (80%), and those with NGU (72%). Anaerobic flora were isolated in 62% of patients, with similar isolation rates in each group. Gram-negative anaerobes were more frequently isolated in men with urethritis, especially NGU, compared to controls (P < 0.05). Prevotella spp. and Bacteroides spp. were significantly more frequently isolated in patients with NGU, including Chlamydia-negative NGU. Fusobacterium spp. were more frequent in the Chlamydia-positive NGU than in the controls (P < 0.05). P. magnus was the most frequent anaerobic species found in the control group, while P. prevotii was most frequently seen in the urethritis group. B. ureolyticus, P. prevotii and P. tetradius were more frequent on the NGU group (P < 0.05). B. ureolyticus was commoner in patients with Chlamydia-negative NGU, while P. tetradius and P. asaccharolytica was commoner in those where C. trachomatis was isolated than in the control group. CONCLUSION: Urethral microflora isolated showed ten bacterial genus and 25 different species of anaerobes. The spectrum of these microflora changed with the presence of urethritis and varied with its aetiology.

Adult↗
PubMed1998

Alterations in erythrocyte aggregability in diabetics: the influence of plasmatic fibrinogen and phospholipids of the red blood cell membrane.

In order to ascertain whether the increased aggregability observed in the red blood cells of diabetic patients is induced exclusively by plasma factors or is also influenced by membrane lipids, we examined the phospholipids of the erythrocyte membrane, the plasma fibrinogen concentration and erythrocyte aggregation in 86 insulin and non insulin-dependent diabetic patients. The data obtained show that the erythrocyte aggregability of the diabetic patients is higher than that of the control group (10.0+/-2.4 vs. 7.8+/-1.6%). This increased aggregability correlates not only with a higher fibrinogen concentration but also with changes observed in the membrane phospholipids. The percentage of sphingomyelin (SP) in the patients is higher than in the controls (22.6+/-6.8 vs. 18.4+/-5.4%) and that of phosphatidylserine (PS) is lower (9.5+/-6.1 vs. 12.1+/-5.1%). No differences in the percentages of the other two phospholipids identified (phosphatidylcholine, PC, and phosphatidylethanolamine, PE) were observed. The increase in the saturated nature of the phospholipids of the erythrocyte membrane, which can be measured by the (SP + PC)/(PE + PS) ratio, is statistically related (r = 0.39; p < 0.05) to the increased red blood cell aggregability observed in these patients.

Adult↗
PubMed1998

The cholesterol/phospholipid ratio of the erythrocyte membrane in children with familial hypercholesterolemia. Its relationship with plasma lipids and red blood cell aggregability.

The cholesterol/phospholipid ratio (C/PL) of the red blood cell membrane, plasma lipids and erythrocyte aggregability were evaluated in 20 children with familial hypercholesterolemia (age: 10.4+/-4.6 years) but without detectable vascular injury. The results indicate that hypercholesterolemic children have a higher erythrocyte membrane C/PL ratio than the control group (0.81+/-0.23 vs. 0.65+/-0.08, p < 0.01). This membrane lipid alteration correlates inversely with the plasma concentration of HDL-cholesterol (r = -0.558, p < 0.010). The patients also showed greater erythrocyte aggregability than the control group (8.21+/-1.11 vs. 6.25+/-1.24, p < 0.001), but this does not seem to correlate with the changes observed in the lipid composition of the cell membrane. These results suggest that from childhood, people with familial hyper-cholesterolemia show alterations in the lipid composition of the red blood cell membrane that are related to the changes observed in plasma lipids and appear prior to atherosclerotic vascular symptoms.

Child↗
PubMed1998

Erythrocyte deformability in young familial hypercholesterolemics.

In order to ascertain whether young familial hypercholesterolemic subjects without atherosclerotic lesions demonstrable on a carotid echo-Doppler show decreased erythrocyte deformability, we determined the erythrocyte elongation index (EEI) by means of a shear stress diffractometer (Rheodyn SSD) in twenty-four children with heterozygous familial hypercholesterolemia (FH), aged 12 +/- 3 years, and their corresponding affected parent. The parents were twenty-three adults with heterozygous FH aged, 32 +/- 6 years. The control group was made up of a similar number of well matched healthy volunteers. The EEI at 6, 12, 30 and 60 Pa showed no statistical differences between FH children and their control group, or between FH parents and their control group. No correlations were found between EEI and plasma lipids or lipoproteins at any of the shear stresses used. These results suggest that the red blood cells of young familial hypercholesterolemic subjects who show no deterioration of the vascular tree are not less deformable than those of healthy normolipemic subjects, and that dyslipemia itself does not produce alterations that damage the rheological properties of the red blood cell.

Adolescent↗
PubMed1998

Plasma thrombomodulin is not increased in familial hypercholesterolemic children with rheological alterations.

In order to ascertain whether hemorheological alterations precede the atherosclerotic lesion in familial hypercholesterolemia (FH), we studied the lipid and hemorheological profile of 29 heterozygous FH children (12 males and 17 females), aged 12+/-3 years, and a well-matched control group (CG), and assessed their plasma thrombomodulin level as an early marker of endothelial injury. No differences were found between FH children's plasma thrombomodulin values (31.7+/-11.2 ng/ml) and those of the CG (27.8+/-15 ng/ml). However, the rheological variables of FH children and the CG were statistically different (p < 0.001) for fibrinogen (Fbg): 266+/-48 mg/dl vs. 205+/-32 mg/dl; erythrocyte aggregation at stasis (EAM0): 4.6+/-1.2 vs. 3.3+/-0.9; erythrocyte aggregation at low shear (EAM1): 7.9+/-1.7 vs. 6.1+/-0.8; and plasma viscosity (PV): 1.18+/-0.03 cP vs. 1.12+/-0.04 cP. Correlations between rheological parameters and lipids were found. The normal values obtained in FH children for plasma thrombomodulin suggest that the hemorheological alterations appear prior to the vascular injury, are in part related to dyslipemia and could contribute to the development of the atherosclerotic process by modifying blood flow conditions.

Adolescent↗