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Biomedical subjects

J Aznar

Publications and source records attributed to J Aznar.

At least 37 records · Page 2Linked to original sources

Protein C inhibitor and other components of the protein C pathway in patients with acute deep vein thrombosis during heparin treatment.

The protein C inhibitor (PCI) concentration and other parameters of the protein C pathway were studied in 19 patients with symptomatic acute deep vein thrombosis before and during the first 5 days of heparin treatment. The mean levels of PCI antigen and activity decreased rapidly and significantly during the first day of heparin therapy from 83 and 84% to 60 and 59% of the pooled normal human plasma (p less than 0.01), respectively, and to 56 and 54% after 5 days of treatment (p less than 0.01). In contrast, antithrombin III decreased progressively 25% during 5 days of heparin treatment. Protein C antigen and activity and total protein S remained unchanged during heparin treatment. Free protein S was decreased before heparin treatment (83%, p less than 0.05) and increased to normal values after 5 days of treatment. C4b-binding protein was significantly increased before and during heparin treatment (p less than 0.01). Activated protein C (APC) complexed to its two major plasma inhibitors, PCI and alpha 1-antitrypsin (alpha 1AT) were measured by specific ELISA's. Before treatment, 18 of the 19 patients studied had increased levels of APC:alpha 1AT complexes with a mean value of 27 +/- 22 ng/ml (range, 6-86 ng/ml) compared to normal values (8 +/- 2 ng/ml) and 12 of the patients also had detectable APC:PCI complex levels with a mean value of 11 +/- 17 ng/ml (range, 5-68 ng/ml). Both APC:inhibitor complexes decreased significantly during heparin treatment.

Acute Disease

Hypercoagulable state after thrombolytic therapy in patients with acute myocardial infarction (AMI) treated with streptokinase.

Fibrinogen activity was studied in 70 patients with AMI who were treated with an intravenous infusion of SK (800,000 U/30 min or 1.5 mill U/60 min). Patients received a continuous infusion of heparin after thrombolytic therapy was completed. 800,000 U and 1.5 mill U SK recanalized infarct-related arteries at a rate of 78%. Early re-infarction occurred in 6% in each group. Upon admission to the hospital patients showed a hypercoagulable state that may be related to an elevated level of fibrinogen and HMW fibrinogen (70.5 +/- 2 vs 65 +/- 2% in patient and normal plasmas, respectively) that changed to a transitory hypercoagulable state indicated by decreased fibrinogen levels after SK treatment. Forty-eight hours after SK, a new fibrinogen hyperfunction, related to an increase in fibrinogen level and especially HMW synthesized fibrinogen (82 +/- 1 or 81 +/- 1%, 800,000 and 1.5 mill U SK, respectively) was observed, which was neutralized by heparin therapy (1,660 U/h with continuous infusion). The elevated levels of fibrinogen (363 +/- 21 vs 240 +/- 8 mg/dl in patient and normal plasmas, respectively) and HMW fibrinogen (70 +/- 3% with both SK hypercoagulable state that is not neutralized by the heparin dose were compared with those whose arteries recanalized. The former group had a higher concentration of fibrinogen (197 +/- 31 vs 147 +/- 18 mg/dl), HMW fibrinogen (78 +/- 0.5 vs 74 +/- 0.3%, respectively), and FPA (130 +/- 3 vs 6 +/- 4 pmol/ml) and more extensive fibrin gel formation kinetics (gelation rate 3.3 +/- 1.4 vs 1.1 +/- 0.2 OD/s x 10(-4), respectively) than the second group. The hypercoagulable state found in patients with acute myocardial infarction undergoing thrombolytic therapy may be related mainly to the progression of HMW fibrinogen and fibrinogen levels.

Adult

Clinical and haemostatic parameters in the HELLP syndrome: relevance of plasminogen activator inhibitors.

Various parameters of the haemostatic and, more importantly, of the fibrinolytic systems were examined in 5 patients with severe pre-eclampsia/eclampsia. All 5 showed signs of haemolysis, elevated liver enzymes and low platelet count (HELLP syndrome). A significant decrease in platelet count (46.4 X 10(9)/litre) and an increase in beta-thromboglobulin (137 ng/ml) were observed in the HELPP patients in comparison with normal pregnant women (267 X 10(9)/litre and 49.3 ng/ml, respectively). No significant differences in fibrinogen levels, activated partial thromboplastin time, prothrombin time and fibrin(ogen) degradation products between the HELLP patient group and the normal pregnant group were observed. However, the antigenic levels of tissue-type plasminogen activator and type 1 plasminogen activator inhibitor were significantly higher in the HELLP pre-eclamptic women than in gestational age-matched controls. In contrast, the antigen levels of type 2 plasminogen activator inhibitor were significantly lower in the patients. These results indicate that platelet activation and alterations in plasminogen activator inhibitors type 1 and type 2 may be involved in the pathophysiological pathway of this syndrome.

Adult

Human fibrinogen heterogeneity. A study of limited fibrinogen degradation.

Different fibrinogen species were examined in normal plasma following urokinase treatment, in isolated high molecular weight fibrinogen treated with plasmin and in plasma samples from patients with acute myocardial infarction receiving thrombolytic therapy. In normal plasmas two main fibrinogen species (Mr = 340,000 and Mr = 320,000) and an intermediate fragment (Mr = 330,000) were observed. The 340,000 fibrinogen was the most sensitive to degradation; it gave rise to 330,000 and 320,000 species. Degradation of isolated 340,000 fibrinogen was similar to plasma fibrinogen degradation. After thrombolytic therapy in acute myocardial infarction patients, when the plasma fibrinogen decreased near to zero, the new synthesized fibrinogen was 340,000 form. 'In vivo' conversion of 340,000 to 320,000 fibrinogen, associated with the transitory 330,000 form, was observed. The coagulation study of plasma fibrinogen showed that when Mr 340,000 fibrinogen decreased (40%), the gelation rate decreased and lag time increased drastically. The high 340,000 fibrinogen content found in acute myocardial infarction patients gave rise to the hypercoagulable state.

Blood Coagulation

Influence of a rehabilitation sports programme on the fibrinolytic activity of patients after myocardial infarction.

The influence of regular physical exercise on fibrinolysis was studied in two groups of patients after myocardial infarction. The two groups were of similar age and living habits. One of the groups took part in a rehabilitative training programme while the other group did not participate in any sports activities. Several fibrinolytic variables, including plasminogen activator inhibitor (PAI) activity and PAI-1 antigen, were studied before and after an ergometric test performed at three different times: at the end of hospitalization (before beginning the rehabilitation programme), three months and six months after myocardial infarction. Our results indicate that by the sixth month fibrinolytic activity, measured by the tissue plasminogen activator (t-PA) capacity, had decreased significantly (p less than 0.025) in the patients who were not participating in the rehabilitation programme whereas it had increased slightly in the patients involved in the rehabilitation programme in comparison with the initial values. It was also observed that while PAI activity remained constant or decreased slightly in patients after six months in the rehabilitative sports programme, these PAI levels increased significantly in patients who were not in the sports programme. Our results indicate that there was a significant decrease in the fibrinolytic capacity of patients who were not participating in the rehabilitation sports programme, while the patients involved in the rehabilitation programme showed a slight improvement in their fibrinolytic activity.

Adult

Functional and immunologic protein S in normal pregnant women and in full-term newborns.

Total and free protein S antigen and C4b-binding protein (C4bp) were determined by rocket immuno-electrophoresis, and functional protein S was assayed by a coagulation method, throughout pregnancy and normal puerperium and in a group of normal full-term newborns (FTN). The functional protein S assay is based on a modification of the APTT, using a mixture of test sample, protein S deficient plasma, activated protein C, phospholipids and calcium. This protein S functional assay is specific for protein S since the APTT prolongation by normal plasma was abolished by incubation of plasma with monospecific, rabbit anti-protein S IgG. The ratios of functional protein S/free protein S antigen in healthy men (n = 13) and women (n = 14) were 1.0 +/- 0.13 (mean +/- SD) and 1.03 +/- 0.20, respectively. During pregnancy there is a decrease in functional protein S and a progressive decrease in total and free protein S antigen, with a functional/free protein S ratio of 0.75 +/- 0.28 in the third trimester of pregnancy (n = 16). In early puerperium the functional protein S level was lower than the free protein S antigen level (ratio about 0.5). In the FTN group, the free protein S level was 39% and protein S activity was about 70% that of adults, with a functional/free protein S ratio of 1.84 +/- 0.31. C4bp values were 23.5 +/- 10.3% in the FTN group, and crossed immunoelectrophoresis showed that in this group the major protein S peak corresponded to free protein S.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The influence of chemotherapy on plasma coagulation and fibrinolytic systems in lung cancer patients.

After the administration of cytostatic drugs, an increase in thromboembolic phenomena has been described in cancer patients. The authors studied the changes in plasmatic coagulation and fibrinolysis in 40 patients with nonoperable Stage III and IV lung cancer after cytostatic chemotherapy. The results show significant postchemotherapy increases in fibrinopeptide A levels, as well as a decrease in fibrinolytic activity reflected by a drop in functional tissue activator. Also the authors studied the potential accumulative effect of three chemotherapy cycles. A significant increase in functional plasminogen activator inhibitor has been noted. Chemotherapy is apparently capable of conditioning a decrease in fibrinolytic activity in these cancer patients that could be related to the enhanced tendency to developing thromboembolic phenomena after cytostatic chemotherapy.

Aged

Arachidonate incorporation into rat aorta lipid fractions and eicosanoid formation. Effect of prolonged prostacyclin production.

Endogenous arachidonic acid (AA) content, incorporation of radiolabelled AA (AA*) into total lipids, main lipid fractions and different phospholipids (PL), and prostanoid formation have been evaluated in fresh (control) rat arteries and in arteries after 180 min of incubation in buffer (exhausted). The results show that PGI2 formation from endogenous AA decreased 90% in exhausted arteries while AA content decreased only 30%. The total AA* incorporation was significantly higher in exhausted arteries than in controls (p less than 0.01). The distribution of AA* in lipids is altered in exhausted arteries; it increases in total PL, particularly in phosphatidylethanolamine, and decreases in phosphatidylcholine and phosphatidylserine + phosphatidylinositol. AA* content was also lower in triglycerides and esterified cholesterol of exhausted arteries than in control arteries. The AA* metabolized to PGI2 was 83% lower in exhausted arteries than in controls, while PGE2 and TXB2 formation were not modified by the exhaustion process. When the effect that longer incubation in plasma (180 min) has on AA metabolism and turnover was evaluated, PGI2 formation from endogenous AA was found to be increased in comparison with arteries incubated for the de same period in buffer, and the changes observed in the distribution of AA in lipid fractions are smaller than those found in buffer-exhausted aortas. The results of the present study indicate that prolonged production of prostanoids leads to an alteration in AA turnover and to an inactivation of the PGI2-forming system. Plasma seems to protect AA metabolism.

Animals

Changes in the plasma levels of type 1 and type 2 plasminogen activator inhibitors in normal pregnancy and in patients with severe preeclampsia.

This report defines the nature of the molecules responsible for the increased plasma plasminogen activator inhibitor (PAI) activity in preeclamptic patients and the relationship of these inhibitors to the severity of placental damage in preeclampsia. Clinical groups consisting of pregnant women with either severe preeclampsia or chronic hypertension with superimposed severe preeclampsia, as well as normal pregnant and nonpregnant women, were analyzed in a panel of functional and immunologic assays for PAI-1 and PAI-2. Pure severe preeclamptic patients in their third trimester showed a significant increase in both antigenic (136 ng/mL) and functional (5.76 U/mL) type 1 PAI (PAI-1) as compared with normal third-trimester pregnant women (34.8 ng/mL and 2.57 U/mL, respectively). In contrast, antigenic (186 ng/mL) and functional (5.76 U/mL) levels of type 2 PAI (PAI-2) were significantly lower in the pure severe preeclampsia group as compared with the values of the normal pregnant group (269 ng/mL and 9.58 U/mL, respectively). The patients with chronic hypertension and superimposed severe preeclampsia exhibited PAI-2 levels comparable to those of the pure preeclamptic group, whereas their antigenic and functional PAI-1 levels were intermediate (94 ng/mL and 3.25 U/mL, respectively) between the normal pregnant and the pure preeclamptic groups. During early puerperium of both normal pregnant women and patients, plasma PAI-1 antigen and activity decreased within one day to approximately the levels detected in normal nonpregnant women, while PAI-2 levels remained elevated for over 11 days. Similar results were obtained in plasma samples obtained from citrated blood and blood collected with an anticoagulant/antiplatelet mixture, suggesting that increased PAI-1 levels in preeclamptic patients were not due to platelet activation in vitro. In preeclamptic patients, a positive correlation between birth weight and PAI-2 values was observed (r = .64, P less than .05), whereas birth weight was inversely correlated with both PAI-1 levels and total PAI activity (r = -.6, P less than .005 and r = -.76, P less than .005 respectively). Preeclamptic patients with extensive placental infarction exhibited higher plasma PAI activity (24.1 U/mL v 11.6 U/mL) and PAI-1 values (305 ng/mL v 80.9 ng/mL) than preeclamptic patients without extensive placental infarction. In contrast, PAI-2 levels were reduced in preeclamptic patients with infarction in comparison with those of patients without infarction (141 ng/mL v 212.9 ng/mL). Our data indicate that increases in the level of PAI-1 accounts for the high plasma PAI activity in severe preeclampsia as measured using single-chain t-PA.

Adult

[In situ hybridization with DNA probe for the diagnosis of Neisseria gonorrhoeae infections].

A comparative study of a DNA probe for the detection of Neisseria gonorrhoeae with Gram stain and modified Thayer-Martin medium was performed. The probe was the 2.6 megadaltons (Mda) cryptic plasmid of N. gonorrhoeae, labeled with a nonradioactive system combining sulphonation of DNA with the antibody detection of sulphonated groups (Organics Chemiprobe). Overall 101 samples were evaluated: 39 urethral exudates, 3 rectal exudates, and 59 cervical exudates, from 42 males and 54 females in whom gonococcal infection was suspected. Simultaneously, Gram stain and culture of the several exudates were carried out. The in vitro sensitivity of the method was evaluated with different dilutions of N. gonorrhoeae, from 1 to 1000 cfu/ml, and a minimum of 50 cfu/ml were detected. In the detection of N. gonorrhoeae in clinical samples, there was a 100% sensitivity and a specificity of 83% (males) and 79% (females), with positive predictive value of 97% in males and 53% in females. The negative predictive value was 100% both for males and females.

DNA Probes

[Evaluation of 2 commercial monoclonal antibody kits for the identification of herpes simplex virus].

Two commercial monoclonal antibody kits (Virgo and Mikrotrak for the identification of Herpes simplex virus (HSV) have been assessed. In 65 positive HSV cultures from clinical samples, 25 strains (38%) were identified as HSV1 with both kits. The Virgo kit identified 37 strains (57%) as HSV2, and did not identify the remaining 3 (5%). With the Microtrak kit, 34 strains (52%) corresponded to type 2, 2 (3%) strains remained nonidentified, and in the remaining 4 isolates (6%) both viral types were identified. The concordance between the two evaluated kits was complete in 86% of strains. In the five strains not identified by immunofluorescence, genome analysis was carried out with endonucleases: Hind III and Xho I. Two of these isolates were identified as HVS1, another as HSV2, and in the remaining two both viral types were identified. Overall 6 mixed infections (9%) were detected, 4 with the Microtrak kit and endonucleases and 2 with only the latter method. The Microtrak system shows some advantages such as quickness, easy readings and the possibility to diagnose infections where both types of virus participate.

Antibodies, Monoclonal

[Genital herpes of mixed etiology].

The relevance of mixed genital infections in our area was evaluated, and we report their clinical and epidemiological features for both viral types. We evaluated overall 54 Herpes simplex virus (HSV) isolates from 44 patients seen at the clinic of sexually transmitted diseases (STD) of the Sevilla School of Medicine during 1986 and 1987. The identification of the isolated strains was made by direct immunofluorescence with type-specific monoclonal antibodies. In those isolates where we detected both viral types confirmation was obtained with the endonuclease analysis: Hind III and Xho I. Four mixed infections were diagnosed, representing 7% of all HVS isolates of genital origin. Two were classified as initial nonprimary infections, and the remaining two were asymptomatic infections. Two patients showed simultaneous infections by other organisms.

Adult

[Determination of free erythrocyte protoporphyrin in thalassemic trait].

Free erythrocyte protoporphirin (FEP), along with diverse haematologic and iron metabolism data, were determined in 60 carriers of the thalassaemic trait (29 beta and 31 delta beta). FEP rates were significantly higher in thalassaemia carriers (39.04 +/- 14.12 micrograms/dl) than in a control group (24.95 +/- 4.70 micrograms/dl) (p less than 0.05). No correlation between FEP and any other iron metabolism parameter, or the severity of anaemia, was found. No FEP differences appeared between the beta (41.06 +/- 16.5 micrograms/dl) and delta beta (37.1 +/- 11.06 micrograms/dl) traits, so, although FEP rates are increased in thalassaemia carriers, they are useless in differentiating between the commonest thalassaemic forms in our country.

Adolescent

[Evaluation of erythrocyte deformability in carriers of thalassemic trait with the Hanss' hemorheometer].

Red-cell deformability was assessed with the Hanss' haemorheometer in 63 carriers of the thalassaemic trait (20 beta and 43 delta beta). Impaired deformability (rigidity index 10.5 +/- 1.4) was present in 80% of the carriers of both beta- and delta beta-traits, as compared with a control group (rigidity index 8.7 +/- 0.6). No correlation was found between such indices and several parameters capable of influencing upon red-cell deformability, namely, MCV, MCH, RDW and MDA. The possibility of any impairment of lipid compounds in red cell membrane is suggested as a cause of decreased deformability in thalassaemia carriers.

Adolescent