[Kinetics of the fibrinolytic activity of the Hageman factor].
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Biomedical subjects
Publications and source records attributed to J Aznar.
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The clinical efficacies of two different single-dose, oral treatments with ciprofloxacin were evaluated in a double-blind randomized study of 50 men with gonococcal urethritis. Two groups of patients were studied. The 25 patients in group A (age, 18-32 years; mean = 26.2) received a single dose of 250 mg of ciprofloxacin; the 25 in group B (age, 16-42 years; mean = 26.3) received a single dose of 100 mg of ciprofloxacin. The minimal inhibitory concentrations of ciprofloxacin for all the isolates were less than or equal to 0.0015 microgram/ml. Neisseria gonorrhoeae was eradicated from all 50 patients; 80% of them were clinically cured, and 20% developed postgonococcal urethritis. There was no significant difference between the two treatments evaluated. We conclude that a single oral dose of 100 mg of ciprofloxacin could be an alternative treatment for uncomplicated gonorrhea in men. Neither treatment prevented the development of postgonococcal urethritis.
Ninety-five patients with nongonococcal urethritis were enrolled in a double-blind study and were randomly assigned to a one-week treatment with ciprofloxacin (500 mg twice daily) or ofloxacin (200 mg twice daily). Two weeks after treatment the results obtained for the 79 evaluated patients were as follows: 59 patients (75%) were clinically cured, and of the 54 patients with initial positive cultures, 39 (72%) remained culture-negative. We did not find any statistically significant differences between the results obtained with the two treatments. These results did not vary with the cause. Patient compliance with the regimens of two doses per day was excellent, and no serious adverse effects occurred with either drug.
This study compares the extent of inhibition of thrombin generation and activity achieved in patients with acute myocardial infarction receiving fibrinolytic treatment (streptokinase SK, or rt-PA) and concomitant intravenous heparin treatment adjusted to the patients' weight with that achieved with the same heparin regimen but without fibrinolytic therapy. The study involved 90 patients, grouped according to their treatment: SK+heparin; rt-PA+heparin, and heparin without thrombolytic agents. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), fibrinopeptide A (FPA) and activated partial thromboplastin time were measured. Patients treated with SK+heparin or rt-PA+heparin and higher F1+2 plasma levels than the patients treated with heparin alone at 12, 48 and 72 h in the case of SK+heparin, and at 12, 24, 48 and 72 h in that of rt-PA+heparin. Compared to baseline, the plasma levels of FPA were decreased in the three treatment groups at 24-48 h. There were no significant changes in TAT and FPA plasma levels among the three treatment groups at the different times. After thrombolytic therapy with both SK and rt-PA, there was an increase in thrombin generation, although high-dose intravenous heparin inhibited the different increases in thrombin associated with the thrombolytic agents to the same extent.
This study examines the evolution of the thrombotic activity in patients with myocardial infarction (MI) treated with aspirin (200 mg/day) for 2 years after MI. Plasma samples of 10 patients were collected at 7, 30, 60, 90, 120, 150, 180, 360 and 720 days. In all the samples we measured fibrinogen (Fg), high molecular weight Fg (HMW-Fg), fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), beta-thromboglobulin (beta-TG), von Willebrand factor (vWF), tissue factor (TF) and TF pathway inhibitor (TFPI). The plasma Fg, HMW-Fg, FPA, F1+2, beta-TG and vWF levels were significantly elevated in the patients at the beginning of the study as compared to the normal group. The 95% confidence intervals were Fg 277-333 mg/dl, HMW-Fg 200-244 mg/dl, FPA 5.3-16.5 ng/ml, F1+2 1.4-1.8 nmol/l, beta-TG 110-118 IU/ml and vWF 139-195%. At thirty days Fg and HMW-Fg returned to normal levels, whereas the increase in FPA and F1+2 levels persisted throughout the study. At 120 and 150 days, respectively, beta-TG and vWF returned to normal levels. The increase in thrombin generation and activity pointed to a persistent hypercoagulable state 2 years after MI. Plasma levels of TF and TFPI showed no statistically significant variations with respect to the normal values over the 2-year period studied. In conclusion, these results suggest a persistent generation and activity of thrombin and cellular activation in these patients after MI.
Some properties of fibrinogen from 30 newborn and 30 normal adult plasmas obtained under the same conditions have been studied. The results show that the high-molecular weight fibrinogen (HMW-Fg) was decreased by nearly 25% in newborn plasma as compared to normal adult values. The kinetics of fibrin gel formation was decreased in newborn as compared with normal adult plasmas (gelation rates 2.2 +/- 1 vs. 5.6 +/- 0.5 x 10(-4) OD/s, lag time 128 +/- 25 vs. 72 +/- 3 s). The release rates of fibrinopeptide A (FPAp +/- FPA) and fibrinopeptide B (FPB) were decreased in newborn fibrinogen (FPAp + FPA 10.8 and FPB 1.2 x 10(-3) s-1) as compared to normal adult fibrinogen (FPAp + FPA 11.8 and FPB 1.7 x 10(-3) s-1). Analysis by SDS-PAGE of the reduced, highly cross-linked fibrin from the newborns showed that only 23% of the alpha-chain participates in the formation of alpha-chain polymers. The results suggest that the retarded release rate of fibrinopeptides and the decrease in the HMW fibrinogen concentration are causes of the prolonged kinetics of fibrin gel formation in newborns.
Plasma beta-thromboglobulin (beta TG), platelet procoagulant activity (PPA) and malondialdehyde were evaluated in a control group and in 59 patients with chronic coronary heart disease (CHD) undergoing long-term anticoagulant therapy (ACT) with acenocoumarol, and within 2 months after its termination. The patients were clinically stabilized after more than 1 year of an acute myocardial infarction. An increase in beta TG and PPA was found in the patients, both with or without ACT, when compared to the control group. In addition, PPA was found to be higher in older and hypercholesterolemic patients on ACT. After ACT suppression, PPA activity increased significantly, particularly in younger and normocholesterolemic patients. The results of the present study suggest that CHD patients on ACT have some platelet hyperactivity and that the termination of ACT induces an increase in platelet function, particularly in PPA.
Patients with ischaemic heart disease have high levels of plasminogen activator inhibitor type 1 (PAI-1). These levels can constitute an independent thrombotic risk factor. In addition, PAI-1 synthesis is greater in the atherosclerotic vessels than in the normal vessels and this can also constitute an atherogenic risk factor. There is a good correlation between insulinaemia and PAI-1, but it has not been demonstrated that the circulating level of PAI-1 depends exclusively on insulinaemia. The increased levels of PAI-1 correlate with other coronary risk factors, especially hypertriglyceridaemia, but high PAI-1 levels are also found in normolipaemic patients. Vascular synthesis of PAI-1 can be promoted by high levels of circulating lipoprotein a. Finally, an exercise programme can increase the fibrinolytic activity of heart disease patients towards normal.
Several parameters of fibrinolytic and protein C pathways were evaluated in three groups of patients with high (HR), moderate (MR) and low (LR) postoperative thrombotic risk undergoing major gynaecological surgery. The HR and MR groups were subjected to low molecular weight heparin (LMW) prophylaxis. A significant increase in plasminogen activator inhibitor type 1 (PAI-1) antigen and activity levels was observed in the HR patient group in comparison with the MR and LR groups in the preoperative and early postoperative period. In all the groups studied, the maximum increase in the levels of PAI-1 was seen on day 1 after surgery. However, the D-dimeric levels reached the highest level on day 7. A significant increase in activated protein C:alpha 1 antitrypsin (APC:alpha 1AT) complex levels was observed in the HR group in comparison with the LR group, and a strong decrease in protein C inhibitor in the early postoperative period was detected in all the groups. In spite of heparin prophylaxis, 2 HR patients were diagnosed as deep vein thrombosis (DVT) during the postoperative period. Both patients showed pre-operative levels of PAI-1 antigen or activity and APC:alpha 1AT complexes above the mean + 1 SD of the pre-operative levels in the HR group. In conclusion, in HR patients a hypofibrinolytic and hypercoagulable state was detected in the pre-operative and early postoperative periods. The prophylactic LMW heparin dose used in the present report (20 mg/day x 7) was insufficient to prevent DVT in the HR group. At present our HR patients are given higher doses of LMW heparin (40 mg/day x 7).
The binding of unstimulated and thrombin-stimulated platelets was studied with immobilized fibrinogen and fibrin on polystyrene. The amount of fibrinogen bound to the polystyrene support was 2 micrograms/tube, which represents 2.35 micrograms/cm2. Immobilized fibrin was obtained by adding thrombin (5 nM) to immobilized fibrinogen. The number of unstimulated 111In-platelets bound to immobilized fibrinogen and fibrin was similar (3.2 +/- 0.3 x 10(6) and 3.1 +/- 0.4 x 10(6) platelets/micrograms fibrin(ogen), respectively). The platelet binding steadily increased. In the first 2 min, the binding rate was 0.23 x 10(6) platelets/micrograms fibrinogen/min. The binding rate then increased rapidly and saturation was reached at 10 min. The extent of the adhesion of resting platelets to immobilized fibrinogen is about one half that of the same platelets stimulated with thrombin. In thrombin-stimulated 111In-platelets, the binding to immobilized fibrinogen and fibrin is time dependent, and saturation is reached at 5 min. The early rate of thrombin-stimulated platelet binding to fibrinogen is about twice that of binding to fibrin (1.25 and 0.74 x 10(6) platelets/micrograms fibrin(ogen)/min, respectively). In saturation conditions, 1 microgram fibrinogen binds 5.7 +/- 0.6 x 10(6) thrombin-stimulated platelets and 1 microgram fibrin binds 4.6 +/- 0.5 x 10(6) thrombin-stimulated platelets. Our results indicate that the rate of platelet aggregation is faster than fibrin formation, and the rate of fibrinogen-platelet binding is faster than that of fibrin-platelet binding. Therefore, after thrombin stimulation, the binding of platelets to fibrin must be secondary to the binding of platelets to fibrinogen.
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Twenty adult surgical patients aged between 15 and 83 years (mean:45), 10 of whom had wound infections (one complicated with septicaemia), 2 with septicaemia, 1 with gynecological infection complicated with endocarditis, 5 with urinary tract infections and 2 with lower respiratory tract infections, were treated with parentally-administered cefotaxime. Aetiology was Proteus 7, E. coli 4, Pseudomonas 3, Enterobacter 2, Klebsiella 2 and 2 Serratia. Susceptibility testing was determined by the agar dilution method, with MIC values ranging from 0.01 to 5 microgram/ml, with two urinary isolates of Pseudomonas with MIC of 20 microgram/ml. Clinical responses were excellent in 13 (65 per cent) cases, moderate in 2 (10 per cent) and 3 (15 per cent) failed to respond to therapy. Clinical assessment was not possible in three patients. Bacteriological responses were excellent in 14 (70 per cent) cases, poor in 4 (20 per cent) and in two there was no follow-up. Systemic tolerance was good in all patients except one.
This study examined ninety-six patients with essential arterial hypertension (WHO grade I-II) who had been under treatment for a period of at least one year before participating in the study. When the study began the patients received no drug treatment for one month. At the end of this washout period their basal situation was evaluated and drug treatment was begun (26 patients on calcium antagonists, 39 on beta-blockers and 31 on angiotensin converting enzyme inhibitors). The patients were evaluated again after one and two years of uninterrupted treatment with the chosen medication. The results obtained indicate that in a basal situation hypertensive patients have higher blood viscosity and erythrocyte rigidity values than the control group. Regardless of the drug treatment used, the patients experienced during the study a progressive deterioration of their hemorheological situation consisting of an increase in red blood cell rigidity and increased blood viscosity. These results indicate the importance of evaluating the hemorheological parameters of hypertensive patients and suggest that it may be advisable to include in their treatment some kind of medication that prevents progressive rheological deterioration.