Biomedical subjects
Publications and source records attributed to J Aznar.
The present report describes a case of cerebral venous thrombosis occurring in a patient suffering from refractory anaemia with excess of blasts (RAEB). This unusual complication suggests that RAEB could be considered a potential prothrombotic state.
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Elevated plasma levels of type 1 plasminogen activator inhibitor (PAI-1) have been implicated in mediating the fibrin deposition and occlusive lesions that occur within the placental vasculature in preeclampsia (PE) and intrauterine growth retardation (IUGR). In this report we identify the cells within the normal-appearing villous tissue that are responsible for the local production of PAI-1 in women with PE and IUGR. Levels for another fibrinolytic inhibitor (ie, type 2 plasminogen activator inhibitor [PAI-2]) were determined for comparative purposes. Elevated levels of PAI-1 were detected in placenta extracts from PE/IUGR patients (121 +/- 38 ng/mg, n = 8) when compared with the levels in placenta extracts from normal women (43 +/- 17 ng/mg, n = 10) or women with IUGR but not PE (51 +/- 22 ng/mg, n = 11). Immunohistochemical analysis of paraffin sections showed an increased immunoreactivity for PAI-1 in the placental villous syncytiotrophoblasts from PE/IUGR women compared with the immunostaining of placental samples from the normal or IUGR group. In contrast, antigen levels and immunostaining for PAI-2 were reduced in the placentas harvested from not only the PE/IUGR women (209 +/- 144 ng/mg) but also the IUGR group (169 +/- 106 ng/mg) in comparison with the PAI-2 levels in normal placentas (535 +/- 98 ng/mg). To document that the increased immunoreactivity for PAI-1 in PE/IUGR syncytiotrophoblasts was mediated by an increased production of PAI-1 within these cells, in situ hybridization analysis was performed. A strong positive signal for PAI-1 mRNA in villous syncytiotrophoblasts from PE patients (n = 5) was obtained after 2 weeks of exposure to the NTB2 emulsion in comparison with the weak signal for PAI-1 mRNA that required a 10-week exposure of the normal placenta sections (n = 10). Northern blotting for PAI-1 mRNA showed that both transcripts (ie, 3.2 and 2.3 kb) were elevated in samples of two PE patients in comparison with the PAI-1 mRNA transcripts present in a normal placenta and an IUGR placental sample. These results show increased PAI-1 and mRNA levels in placentas from PE patients and raise the possibility that localized elevated levels of PAI-1 may play a role in the initiation of placental damage, as well as in the thrombotic complications associated with this disease.
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A prospective study of the frequency, timing, etiology and risk factors of infections in renal transplant recipients during the first year after transplantation was conducted in 50 consecutive patients. Neither prophylaxis with trimethoprim-sulfamethoxazole nor antiviral prophylaxis was administered. Two hundred twenty-eight episodes of infection were registered (4.5 per patient), 19 of which were severe. Forty-seven percent of all infectious episodes occurred during the first two months after transplantation. The more frequent infections were bacterial (64%), viral (22%) and fungal (11%). Escherichia coli was the most common agent isolated (n = 36), followed by cytomegalovirus (n = 32). Urinary tract infections were most common (n = 144), especially asymptomatic bacteriuria (n = 106). Surgical reintervention and the use of anti-lymphocytic globulins were associated with a higher frequency of severe infections (p < 0.05), and invasive candidiasis was associated with allograft loss (p < 0.03). Annual survival rates of patients and allografts were 100% and 94%, respectively. The frequency of mild infections was higher than that observed in other studies using bacterial or viral prophylaxis. Nevertheless, the number of severe infections and the survival rates of patients and allografts were similar to those reported in previous studies.
Several fibrinolytic parameters were determined in plasma and amniotic fluid from normotensive pregnancies complicated by intrauterine fetal growth retardation (IUGR) and severe preeclamptic (PE) patients with IUGR and compared with data from normal pregnancies. A significant decrease in plasminogen activator type 2 (PAI-2) and urokinase levels in plasma and amniotic fluid was observed in IUGR groups in comparison with normal pregnancy. No significant differences were observed between the control and IUGR groups in relation to the other fibrinolytic parameters, except for plasma PAI type 1 and tissue-type plasminogen activator levels, which were significantly increased in the PE group. A significant positive correlation was observed between birth weight and PAI-2 levels in both plasma and amniotic fluid, but the plasma PAI-2 levels showed a higher correlation. In conclusion, these results suggest that the PAI-2 level measured in plasma is a more adequate marker of placental function than the PAI-2 level measured in amniotic fluid.
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In 15 patients with acute myocardial infarction who received 1,500,000 U of streptokinase, the gradual appearance of newly synthesized fibrinogen and the fibrinopeptide release during the first 35 h after SK treatment were evaluated. At 5 h the fibrinogen circulating in plasma was observed as the high molecular weight fraction (HMW-Fg). The concentration of HMW-Fg increased continuously, and at 20 h reached values higher than those obtained from normal plasma. HMW-Fg represented about 95% of the total fibrinogen during the first 35 h. The degree of phosphorylation of patient fibrinogen increased from 30% before treatment to 65% during the first 5 h, and then slowly declined to 50% at 35 h. The early rates of fibrinopeptide A (FPA) and phosphorylated fibrinopeptide A (FPAp) release are higher in patient fibrinogen than in isolated normal HMW-Fg and normal fibrinogen after thrombin addition. The early rate of fibrinopeptide B (FPB) release is the same for the three fibrinogen groups. However, the late rate of FPB release is higher in patient fibrinogen than in normal HMW-Fg and normal fibrinogen. Therefore, the newly synthesized fibrinogen clots faster than fibrinogen in the normal steady state. In two of the 15 patients who had occluded coronary arteries after SK treatment the HMW-Fg and FPAp levels increased as compared with the 13 patients who had patent coronary arteries. These results provide some support for the idea that an increased synthesis of fibrinogen in circulation may result in a procoagulant tendency. If this is so, the HMW-Fg and FPAp content may serve as a risk index for thrombosis.
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Platelet activation and the subsequent platelet recruitment induced by activated platelets released products constitute the initial events of platelet thrombus formation. We have evaluated the recruiting activity of collagen-stimulated whole blood in patients with ischemic cerebrovascular insufficiency. This was done using an experimental approach that allows independent evaluation of platelet activation and recruitment. The effects of of treating the patients with dipyridamole (DIP) (300 mg/day), pentoxifylline (POX) (1200 mg/day) or a combination of the two drugs at the same doses was also evaluated before and after 7, 15, and 45 days of treatment. DIP decreased the recruiting activity in a time-dependent manner, while POX did not show any effect. However, the combined treatment with DIP+POX was more effective than DIP alone in reducing platelet recruitment, which was abolished after 45 days of treatment. Studies using the drugs in vitro indicated a greater inhibitory activity of the drug association than either drug individually. The effects of the drug association in vitro, even at high concentrations, was lower than those observed ex vivo after 45 days of treatment. This suggests that DIP+POX in vivo may have effects that condition a reduced platelet response.
Erythrocyte aggregation (EA) was determined in a Myrenne aggregometer at stasis (EAMo) and low shear (EAM1) in 102 patients suffering from primary hyperlipoproteinemia (PHLP)-46 with familial hypercholesterolemia (FH); 28 with familial combined hyperlipemia (FCHL); 28 with primary hypertriglyceridemia (PHTG)-and in a control group (CG) of healthy matched subjects. EA was also determined in FH after the autologous plasma had been replaced by a control plasma. The following parameters were also measured: fibrinogen (Fbg), plasmatic lipids, apolipoproteins, glucose, HbA1 c and membrane erythrocyte lipids: cholesterol (C) and phospholipids (PL). An increase in both EAMo and EAM1 was observed in all the studied groups of patients. When erythrocytes of FH were resuspended in control plasma, EA normalized, but only in 75% of them. Fbg was elevated only in FH and FCHL. Membrane C was increased mainly in FH and FCHL. EA correlates with both Fbg and apolipoproteins. In FH, EA also correlates with membrane C/PL. In addition, a high significant correlation exists between EA and HbA1 c in FCHL. The results obtained suggest that not only Fbg and apolipoproteins but also possible changes in erythrocyte membrane could encourage EA in PHLP.
Two functional assays for protein C inhibitor (PCI) were evaluated in parallel for the same plasma samples. One assay is specific for active PCI and measures its ability to form complexes with activated protein C (APC) in the presence of heparin (España et al, Thromb Res 64, 309, 1991) (Method A). After incubation of samples with heparin and an excess of APC, the amount of APC:PCI formed is measured by an ELISA. The second functional PCI assay is based on the determination of the residual amidolytic activity of the APC added to the sample. In all cases a good correlation was obtained with both methods. For 20 healthy subjects and 20 patients before surgery, there were no significant between-assay differences in the levels of functional PCI activity. On the other hand, there were significant between-assays differences in the levels of functional PCI of the 20 patients measured 1 and 3 days after surgery. In this case, method B gave higher values than method A (38% +/- 13% versus 29% +/- 11% at day 1 and 59% +/- 16% versus 43% +/- 12% at day 3) (mean +/- SD). The level of alpha 1-antitrypsin (alpha 1 AT), the second major plasma APC inhibitor, was significantly increased in patients at day 1 and day 3 (133% +/- 30% and 190% +/- 57%, respectively). Furthermore, there was a positive correlation between the level of alpha 1AT and the normalized difference between the level of functional PCI measured by method B and that measured by method A. Additionally, when normal plasma was supplemented with increasing amounts of purified alpha 1AT, the level of PCI activity measured by method B increased parallel to the increase in alpha 1AT added, but that measured by method A did not. Determination of APC:inhibitor complexes in aliquots of the final mixtures utilized in the PCI assays revealed that the level of APC:alpha 1AT complex increased parallel to the increase in the amount of alpha 1AT added, whereas the APC:PCI complex level remained unchanged. We conclude that current functional PCI assays based on the determination of APC residual activity in plasma are not specific for PCI, are influenced by the level of plasma alpha 1AT and are not reliable for the determination of functional PCI levels in patients with altered levels of alpha 1AT.(ABSTRACT TRUNCATED AT 400 WORDS)
Although the vasopressin analogue desamino-d-arginine vasopressin (DDAVP) induces a very well characterized increase in factor VIII (FVIII), von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), the mechanism(s) by which DDAVP enhances the plasma levels of these proteins is poorly understood. Some clinical evidence suggests that certain patients repeatedly treated with DDAVP at closely spaced intervals become progressively unresponsive (tachyphylaxis). In order to investigate the effect of repeated DDAVP infusion on the behaviour of FVIII, vWF, t-PA and u-PA, we infused three different doses of DDAVP (0.3 microgram/Kg) to six healthy volunteers (19-26 years old, mean 22) at 12-hour intervals. Blood samples were collected immediately before and after DDAVP. The second and third infusion of DDAVP induced a low response of FVIII and vWF. In contrast, t-PA and u-PA exhibited a consistent response after each DDAVP infusion. If the progressive decrease of FVIII and vFW response observed in healthy subjects after repeated doses of DDAVP at 12-hour intervals is extended to haemophiliacs and von Willebrand's patients, the usefulness of desmopressin may be limited when these proteins must be raised therapeutically for a prolonged period of time. Finally, our results suggest that the mechanism for regulating the release of vWF and plasminogen activators in the conditions of our study are not dependent.
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BACKGROUND AND METHODS: We have carried out a prospective study of dual genitotropic human papillomavirus (HPV) infections by means of two different DNA detection methods in biopsy specimens obtained from patients who were examined for genital warts at the STD clinic of the School of Medicine in Seville, between January 1990 and December 1991. RESULTS: 100 patients with a clinical diagnosis of condilomata acuminata were seen during the study period. DNA of the genitotropic HPV 6/11, 16/18 and 31/33/35 was detected by an in situ hybridisation method in 75 (77%) of the 98 evaluable samples; one of the genotypes tested in 59 (61%) samples, and two or more genotypes tested in the remaining 16 (15%) samples. In 21 (98%) of the 23 negative samples by in situ hybridisation, we were able to detect DNA of genital HPV using a polymerase chain reaction amplification method (PCR). Among the 34 samples where PCR was applied we confirmed the presence of two different HPV genotypes in eight samples. CONCLUSIONS: The frequency of dual infections with human genitotropic papillomavirus in genital warts was 8%, although we believe that this rate should be higher as we have not used the PCR method in all of the samples.