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Biomedical subjects

J Aznar

Publications and source records attributed to J Aznar.

At least 73 records · Page 4Linked to original sources

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↗

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↗

Hemorheological changes in children with polygenic hypercholesterolemia.

In order to ascertain whether polygenic hypercholesterolemia (PH), the most common cause of small increases in plasma lipids during childhood, is associated with rheological alterations, we determined the hemorheological and lipid profile of 21 PH children (12 males, 9 females) and a well-matched control group (CG). In addition, a carotid ultrasound was done on all the PH children, but showed no alterations. When compared with the CG, PH children showed increased erythrocyte aggregation both at stasis (EAM0) (4.39+/-1.15 vs. 3.75+/-1.02), p < 0.05, and at low shear rate (EAM1) (8.22+/-1.42 vs. 7+/-1.39), p < 0.01, and increased plasma viscosity (PV) (1.19+/-0.04 cP vs. 1.15+/-0.04 cP), p < 0.01. These results reinforce the hypothesis that lipid metabolic alterations are associated with specific rheological modifications in absence of a demonstrable atherosclerotic lesion.

Apolipoproteins↗

[Characterization of the rpoB gene mutations in clinical isolates of rifampicin-resistant Mycobacterium tuberculosis].

OBJECTIVES: Characterization and frequency of the rpoB gene mutations associated with rifampin resistance in Mycobacterium tuberculosis clinical isolates in Sevilla. METHODS: Characterization of rpoB mutations in 21 rifampicin-resistant strains of M. tuberculosis isolated during a three-year period (1994-1996) by three different molecular methods: a nonradioactive Single-strand conformation polymorphism (SSCP) analysis, DNA sequence analysis and a commercial method the line probe assay InnoLiPA. RESULTS: Five distinct rpoB mutations were identified. Ser531-->Leu mutation was detected in 14 strains (66.7%), H526-->Asp in 3 strains (14.3%), Ans512-->Ser in 1 strain (4.8%), Glu513-->Leu in 1 strain (4.8%). A nine nucleotide deletion (codon 510-513) was found in one strain (4.8%) while in the remaining resistant strain (4.8%) no mutation was detected. CONCLUSIONS: The frequency of the different mutations found in the rpoB gene, associated with rifampicin resistance in Mycobacterium tuberculosis clinical isolates in Seville, are similar to those previously reported. However, two new mutations has been detected: a nine nucleotide deletion (codon 510-513), and the Asn512-->Ser point mutation. The characterization of the mutations in the rpoB gene could serve as epidemiological marker for the rifampicin resistant clinical isolates of M. tuberculosis.

Amino Acid Substitution↗

Hemorheological alterations and hypercoagulable state in deep vein thrombosis.

Deep vein thrombosis (DVT) seems to be related to a hypercoagulation and definite hemorheological alterations, but the importance of these alterations in the development of thrombotic events in the deep vein system has not been established. The present study examines both aspects in a group of 55 patients with DVT; the presence of a hypercoagulable state was assessed by quantifying the prothrombin fragment 1+2 (F1+2) and the thrombin-antithrombin III complex (T-AT), and the main hemorheological parameters were evaluated in the acute state and 6 and 12 months later. The results show marked hemorheological, F1+2, and TAT alterations in the acute phase. After 12 months the pattern shows a modest improvement, but erythrocyte aggregation, fibrinogen, F1+2 and T-AT remain increased with respect to the control group (8.51 +/- 1.43; 331 +/- 81 mg/dl; 1.33 +/- 0.60 nmol/l; 3.54 +/- 1.71 ng/ml vs. 8.10 +/- 1.40; 230 +/- 38; 0.94 +/- 0.40; 1.56 +/- 0.59, respectively). These data suggest that the thrombotic event could be influenced by the previous rheological situation and hypercoagulable state.

Acenocoumarol↗

Prothrombotic effects of erythrocytes on platelet reactivity. Reduction by aspirin.

BACKGROUND: Aspirin effectively reduces the incidence of secondary vascular occlusive events in only 25% of patients. Low-dose aspirin as currently used blocks platelet production of prothrombotic thromboxane A2 and allows endothelial synthesis of antithrombotic prostacyclin. This regimen minimizes gastrointestinal toxicity. We previously showed that intact erythrocytes markedly enhance platelet reactivity. Therefore we investigated whether supplementation of low-dose aspirin with a single high dose at 2-week intervals could more effectively block erythrocyte promotion of platelet reactivity. METHODS AND RESULTS: Effects of different aspirin regimens on erythrocyte enhancement of platelet reactivity in normal volunteers were measured with the use of an assay that evaluates both platelet activation and recruitment. After 15 days of daily ingestion of 50 mg aspirin, reactivity of platelets alone was inhibited. However, erythrocyte promotion of platelet activation and recruitment was only inhibited by approximately 50% and persisted in the total absence of thromboxane synthesis. In contrast, if 50 mg/d aspirin was preceded by a single loading dose of 500 mg aspirin, the erythrocyte prothrombotic effect was strongly inhibited (approximately 90%) for 2 to 3 weeks. However, over time, erythrocytes "escaped" from this inhibition, and once again became prothrombotic, even on a daily regimen of 50 mg aspirin. CONCLUSIONS: For clinical purposes, we recommend a loading dose of aspirin (500 mg), followed by daily administration of 50 mg. The loading dose should be repeated at 2-week intervals. This regimen blocks recovery of the erythrocyte capacity to promote platelet reactivity and may amplify the therapeutic potential of aspirin in cardiovascular disease.

Adult↗

Activated protein C resistance phenotype in patients with antiphospholipid antibodies.

The effect of antiphospholipid antibodies (aPL) on the action of activated protein C (APC) was examined in 32 patients: 19 with lupus anticoagulant (LA), 6 with anticardiolipin antibodies (aCL), and 7 with LA and aCL. Eighteen patients had a ratio of activated partial thromboplastin time (APTT) with APC to APTT without APC (APTT ratio) <2.06 (cut-off level) and no factor V Leiden mutation; these patients showed APC-resistance (APC-R) phenotype. The mean prolongation of APTT after addition of APC in a control group was 45.3 seconds, with a lower limit of 31.4 seconds. Only 3 of the 18 patients with low APTT ratio had a prolongation of <31.4 seconds; they were classified as true APC-R phenotype, whereas the other 15 patients were classified as spurious APC-R. Of the 3 patients with true APC-R, 2 had deep venous thrombosis, 1 with pulmonary embolism, and the third had recurrent abortion. Of the other 15 patients, 2 had had ischemic stroke, 1 had recurrent abortion, and 12 were asymptomatic. Circulating APC level was measured in 14 of the 18 aPL patients with a low APTT ratio; it was lower than the normal lower limit in 4 patients and within the lower limit in 2. Three of the 4 patients with reduced APC levels had a history of thrombosis. We conclude that patients with aPL who show APC-R phenotype due to a low APTT ratio without the factor V Leiden mutation can be classified into two groups: true and spurious APC-R phenotype. Since those with true APC-R phenotype could have greater thrombotic risk, adequate classification of these patients is important. Moreover, aPL can sometimes interfere with the activation of protein C, thus reducing the circulating levels of APC, and this could constitute another thrombotic risk factor.

Abortion, Habitual↗

The effect of thrombin on the dynamic exchange between intraplatelet and extraplatelet fibrinogen.

We examined the distribution of platelet fibrinogen and the exchange between intra- and extra-platelet fibrinogen in unstimulated and thrombin-stimulated platelets. In unstimulated platelets 60% of platelet fibrinogen was found in the soluble platelet fraction and 40% in the insoluble one. In platelets activated with thrombin, changes took place in the distribution of intraplatelet fibrinogen but not in the total fibrinogen content. At > or = 0.5 U/ml of thrombin the fibrin(ogen) content of the insoluble and soluble fractions was approximately 80% and 20%, respectively. When we evaluated how extraplatelet fibrinogen affects the content and distribution of intraplatelet fibrinogen, we found that when unlabelled fibrinogen was added to unstimulated and thrombin-stimulated platelets the content and distribution of intraplatelet fibrinogen remained unaltered. However, when 125I-fibrinogen was added, it was incorporated into unstimulated and thrombin-stimulated platelets. In unstimulated platelets, 70% of the incorporated 125I-fibrinogen was in the soluble fraction and 30% in the insoluble. In thrombin-stimulated platelets the distribution of the incorporated 125I-fibrinogen was 62% and 38% in soluble and insoluble fractions respectively. MoAb to GPIIb-IIIa produced 80% and 60% inhibition of 125I-fibrinogen incorporation by unstimulated and thrombin-stimulated platelets. Our data showed dynamic exchange between intraplatelet and extraplatelet fibrinogen both in unstimulated and thrombin-stimulated platelets mediated mainly by GPIIb-IIIa.

Blood Platelets↗

Molecular epidemiology of Mycobacterium tuberculosis strains isolated during a 3-year period (1993 to 1995) in Seville, Spain.

The genetic polymorphism of Mycobacterium tuberculosis strains isolated in Seville, Spain, was studied by using computer-assisted analysis of the IS6110 fingerprint in order to determine the current situation and to evaluate the human-to-human transmission of this pathogen. One hundred seventy-six isolates from 175 patients among the 205 patients diagnosed with tuberculosis (TB) during a 3-year period (1993 to 1995) were cultured and analyzed. One hundred nine patients (62%) were infected with genetically different isolates, and 67 isolates (38%) were grouped into 19 clusters. These results demonstrate that the level of clustering of strains in Seville is intermediate between those in developed and developing countries. Epidemiological relatedness was shown for isolates from only 10 of these clusters. Active and high transmission rates exist in children and in human immunodeficiency virus (HIV)-infected adults, while in non-HIV-infected adults this transmission rate is moderate. Although transmission from children to adults is uncommon, the probability of transmission from HIV-infected patients to young adults not infected with HIV may be higher. On the basis of these observations, we predict a constant rise in the rate of TB transmission among HIV-infected patients and probably in young adult patients not infected with HIV if measures for the effective prevention of TB among the HIV-infected population are not implemented.

Adolescent↗

Modulatory effect of erythrocytes on the platelet reactivity to collagen in IDDM patients.

Platelets participate in the atherothrombotic complications of diabetes. Recent data demonstrate that platelet reactivity can be modulated via cell-cell interactions with erythrocytes and neutrophils. In this study, platelet reactivity was evaluated in 30 IDDM patients. We used an analytical procedure that permits an independent evaluation of platelet activation (granule release, eicosanoid formation) and platelet recruitment (pro-aggregatory activity of cell-free releasates) after platelet stimulation with collagen in the presence or absence of other blood cells. The interaction between platelets and erythrocytes (hematocrit 40%) resulted in a marked enhancement of platelet activation (5HT, betaTG, TXA2 release) and recruitment in both patients and control subjects. The erythrocyte enhancement of platelet TXA2 synthesis and recruitment was significantly higher in the patients, while no differences were detected in platelet granule release. The elevated platelet recruitment in the IDDM patients was found to be due to 1) increased susceptibility of diabetic platelets to the prothrombotic effect of erythrocytes and 2) the greater response of diabetic platelets to their own cell-free releasate. Patients with poor metabolic control (elevated HbA1c) or longer evolution time had an even greater platelet recruitment. The presence of microalbuminuria is not related to the platelet recruitment. Since platelet recruitment is an essential step in thrombus growth, its enhancement may favor thrombotic complications in IDDM.

Adolescent↗

Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: a Bayesian analysis.

The aim of this study was to evaluate the diagnostic value of three tumour markers, squamous cell carcinoma (SCC) antigen, carcinoembryonic antigen (CEA) and CYFRA 21.1, in lung cancer using a Bayesian analysis to obtain the predictive values for different pretest probabilities or prevalences. A cross-sectional study included 94 patients with lung cancer, 40 with benign lung disease, and 40 healthy controls. SCC antigen and CEA were measured in blood samples by microparticle enzyme immunoassay (MEIA), and CYFRA by enzyme-linked immunosorbent assay (ELISA). The results of tumour marker determinations were expressed as percentiles, and showed significantly higher levels in the cancer group than in the two control groups. Taking the 95th percentile of benign lung diseases as the cut-off point (specificity 95%), the following sensitivities were found: SCC 41%, CEA 31% and CYFRA 79%. After a Bayesian analysis, the best results for the three tumour markers were found in prevalences of 30-40%. The highest incremental gain was obtained by CYFRA (at prevalence of 36%, positive and negative predictive value approximately 90%). The three tumour markers were included in a stepwise regression analysis to predict lung cancer, and CYFRA was the only selected variable. We conclude that CYFRA 21.1 may be a useful marker in lung cancer when there is an intermediate pretest probability of disease.

Adenocarcinoma↗

[False tuberculosis outbreak caused by specimen contamination in a micro-bacteriology laboratory: confirmation by molecular techniques].

BACKGROUND: The authors describe a false outbreak of tuberculosis by contamination in sample processing. METHODS: The longitudinal polymorphisms of restriction fragments (RFLPs) of 6 strains of Mycobacterium tuberculosis isolated in different patients over a three week period and which were apparently implicated in an outbreak of tuberculosis were analyzed. RESULTS: Four of the strains studied presented identical restriction pattern and the remaining two presented totally different patterns. Following study of the clinical histories and the epidemiologic relationships three cases of tuberculosis were confirmed. The other three strains isolated corresponded to contamination during the sampling process. CONCLUSIONS: In a possible outbreak of six cases of tuberculosis, molecular techniques have allowed identification of three true cases of tuberculosis and have demonstrated contamination during the sampling process in three other cases. The latter could not have been shown with the clinical and phenotypical data of the strains.

Adult↗

Reference ranges for the concentrations of total and complexed plasma prostate-specific antigen and their ratio in patients with benign prostate hyperplasia.

OBJECTIVE: To establish the normal distribution and reference ranges of complexed and total prostate-specific antigen (PSA) and the complexed-to-total PSA ratio according to the age of the patients, so that PSA can be used to distinguish between prostate cancer and benign prostate hyperplasia (BPH). MATERIAL AND METHODS: Using specific ELISAs, total PSA and PSA complexed to alpha 1-antichymotrypsin (complexed PSA) were determined in 237 BPH patients, 160 with histologically confirmed BPH and 77 in whom prostate cancer was excluded by digital rectal examination, transrectal ultrasound and total PSA measurement. RESULTS: Both total and complexed PSA correlated with patient age (r = 0.424 and r = 0.379, p < 0.0001, respectively). However, no correlation was found between the complexed-to-total PSA ratio and age (r = 0.026, p > 0.2). The mean complexed-to-total PSA ratio for the 237 BPH patients was 0.69 +/- 0.11, and only 23 had a ratio > 0.8. CONCLUSIONS: These results show that the cut-off point of 0.8 established for the complexed-to-total PSA ratio is the same for men of all ages, and that the use of this ratio may avoid many negative prostate biopsies, confirming that PSA: alpha 1ACT is a potential marker for differential diagnosis of prostate carcinoma and BPH.

Adult↗

The impact of parasites on marine mammals: a review.

The design and implementation of conservation plans for marine mammals is a matter of public concern. However, very little is known about the role of parasites in the dynamics of marine mammal populations. This is probably due to methodological constraints concerning sampling biases, poor knowledge of the biology of the hosts and parasites and difficulty and costy of experimental studies. However, current evidence supports the theory that parasites may regulate marine mammal populations. Crassicauda species in cetaceans and Uncinaria lucasi in pinnipeds seem good candidates as regulating agents. In addition, parasite-induced mass mortalities may be important in marine mammal populations. Well documented cases are the PDV virus which decimated the European common seal (Phoca vitulina) populations in 1988 and the Mediterranean striped dolphin (Stenella coeruleoalba) morbillivirus infection of 1990-1992. Due to the social organisation patterns of marine mammals it is possible that such die-offs occur at very low densities, representing a potential threat to endangered species like the Mediterranean monk seal (Monachus monachus), the Hawaiian monk seal (M. schauinslandi) or the Finish Saimaa seal (Phoca hispida saimensis). It is concluded that parasites can play an important role in marine mammal populations not only at the ecological scale but at the evolutionary one too.

Animals↗

Erythrocyte membrane cholesterol/phospholipid changes and hemorheological modifications in familial hypercholesterolemia treated with lovastatin.

Fourteen patients with familial hypercholesterolemia treated with lovastatin (40 mg/day) for three months were studied to find out whether the expected changes in plasma lipids are accompanied by modifications in the lipid composition of the erythrocyte membrane and whether these in turn induce changes in the rheological behavior of the red blood cell. Our results demonstrate the efficacy of lovastatin in reducing the plasma concentration of cholesterol and LDL cholesterol. The changes observed in the plasma lipids correlate with a significant decrease in the cholesterol/phospholipid ratio of the red blood cell membrane, from 1.19 +/- 0.19 in a basal situation to 0.92 +/- 0.23 (p < 0.01) at the end of treatment. These changes in the lipid composition of the cell are statistically related to a decrease in erythrocyte aggregability and an improvement in blood filterability, which means beneficial change in the patients' hemorheological situation.

Adult↗