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Biomedical subjects

J Mateo

Publications and source records attributed to J Mateo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Normalisation of tissue factor pathway inhibitor activity after glycaemic control optimisation in type 1 diabetic patients.

UNLABELLED: Increased plasma concentrations of various markers of endothelial damage have been observed in type I diabetic patients, particularly in those with microangiopathy. OBJECTIVE: To evaluate the effect of near-normalisation of glycaemic control on different markers of endothelial injury involved in haemostasis in poorly-controlled type 1 diabetic patients. MATERIAL AND METHODS: TFPI, thrombomodulin (TM), plasminogen activator inhibitor, tissue-type plasminogen activator and von Willebrand factor were measured in 14 poorly-controlled type 1 diabetic patients free of diabetes-related complications (8 men, 6 women; mean age 29.8 +/- 9.9 years) before (baseline) and after 3 months of intensive therapy and in 14 sex-, age- and BMI-matched control subjects. RESULTS: After a mean follow-up of 107 +/- 49 days (56-210), HbA1c decreased from 11.2 +/- 2.3 to 6.7 +/- 0.7% (p <0.0001). TFPI activity at baseline was higher than in the control group (126.9 +/- 34 vs 92.0 +/- 13%, p <0.005) and decreased after good glycaemic control was achieved (p <0.005), becoming similar to that in the control group (91.0 +/- 16.5%). The TFPI descent correlated with the variations observed in HbA1c (p <0.05; r = 0.54). TM levels at baseline were significantly higher than in the control group (42.3 +/- 9.1 vs 29.00 +/- 10.9; p <0.005) and did not change. The remaining parameters studied were similar between patients and controls and did not change after glycaemic optimisation. CONCLUSIONS: Optimisation of glycaemic control normalises the increased activity of TFPI but not the higher TM levels observed in poorly-controlled type I diabetic patients without chronic complications.

Adolescent↗
PubMed2000

The effect of two different doses of aprotinin on hemostasis in cardiopulmonary bypass surgery: similar transfusion requirements and blood loss.

BACKGROUND AND OBJECTIVES: Various dosages of aprotinin have proven to be effective in reducing blood loss and allogeneic transfusion requirements in cardiopulmonary bypass surgery, despite the controversy surrounding the precise hemostatic mechanisms of this drug. The aim of our prospective, randomized, double-blind study was to assess differences in blood loss and transfusion requirements and the effect of two dosages of aprotinin on hemostatic activation. DESIGN AND METHODS: Patients undergoing coronary artery bypass grafting received high-dose aprotinin (n=28), pump-prime-only (PPO) aprotinin (n=28), or placebo (n=28). RESULTS: The high-dose and the PPO groups had a significantly lower blood loss (985 mL [95%CI 845-1,102] and 1,255 mL, [95% CI 1,025-1,406], respectively) than the placebo group (1,416 mL, 95%CI 1,248-1,612]. Transfusion requirements were lower in the aprotinin-treated groups than in the patients receiving placebo (21 units and 15 units in the high and low-dose groups vs 59 units in placebo group). As far as concerns parameters of thrombin generation, the aprotinin groups showed a significant reduction of F1+2 prothrombin fragment but not of thrombin-antithrombin complexes. There were higher levels of natural anticoagulants, i.e. antithrombin, protein C and protein S, in the high-dose aprotinin group. As regards fibrinolysis parameters, D-dimer was lower in the aprotinin groups, and the levels of alpha2-antiplasmin and plasmin-alpha2-antiplasmin complexes were raised. In summary, both dosages of aprotinin were equally effective in reducing blood loss and transfusion requirements. There was a lower activation of coagulation and fibrinolysis in cardiopulmonary bypass patients treated with aprotinin: the levels of natural anticoagulants were less decreased in the high-dose group. No differences in thrombotic complications were observed between aprotinin groups. INTERPRETATION AND CONCLUSIONS: Our study shows that both dosages of aprotinin are safe and effective in reducing transfusion requirements. Considering the difference in cost of using a low-dose or high-dose schedule, the former should be recommended for patients undergoing cardiopulmonary bypass surgery.

Adult↗
PubMed1999

Lack of association between venous thrombosis and subsequent malignancy in a retrospective cohort study in young patients.

Since the publication of Trousseau in 1865, several studies have documented an increased incidence of cancer in patients with deep venous thrombosis (DVT) especially those with idiopathic or recurrent DVT, but in young patients this association is not clear and is therefore a subject of controversy. We performed a retrospective study in a consecutive cohort of 40 young patients (age <40 years) with a DVT and without a known cancer. All patients were diagnosed in our hospital during the period of 1988-1992. At the time of diagnosis, a routine examination to detect the presence of malignant disease was made. For the follow-up, all patients included in the study were asked to return to our unit and were interviewed for symptoms that could suggest a malignant disease. The mean follow-up was five years (from three to eight years). Twenty-four patients had DVT in the lower limbs and three in the upper extremities, nine had pulmonary embolism (six of them with DVT) and four had DVT in other sites. Sixteen patients (40%) had secondary DVT due to nonbiological causes, abnormalities in hemostasis were found in 14 patients (35%), and biological or environmental triggering factors were not identified in 10 patients (25%). Malignancies were not detected at diagnosis and in the follow-up. In our experience, venous-thrombotic patients under the age of 40 have a low incidence of subsequent cancer. Further studies should be performed to confirm this observation and to ascertain whether extensive screening for cancer is a cost-effective approach.

Adult↗
PubMed1999

Functional expression of a cDNA encoding a human ecto-ATPase.

1 The metabolism of extracellular nucleotides plays an important role in nucleotide signalling mediated by P2 receptors. The nucleotide sequence encoding a putative human ecto-ATPase named CD39L1 was reported recently. However, the biological activity of this protein has not been established. 2 Based on the sequence of CD39L1 we isolated from mRNA from human ECV-304 cells a sequence encoding a 495 amino acid protein that is identical to CD39L1, with the exception that this sequence contains a 23 amino acid stretch in the putative extracellular loop that is missing in CD39L1. Partial sequence of a genomic DNA clone indicates that the CD39L1 gene corresponds to an alternative spliced form of the human ecto-ATPase. 3 Stable expression of isolated sequence in NIH-3T3 mouse fibroblasts conferred a marked nucleotide hydrolytic activity consistent with the activity of an ecto-ATPase. 4 The human ecto-ATPase hydrolyzed all naturally occurring nucleoside triphosphates in a Ca(2+)- or Mg(2+)-dependent manner. Nucleoside diphosphates were hydrolyzed at a rate approximately 5% of that of the corresponding triphosphates. The apparent Km and Vmax values were: 394+/-62 microM and 107+/-7 nmol Pi min-1 10(6) cells-1 for the hydrolysis of ATP, and 102+/-33 microM and 4+/-0.4 nmol Pi min-1 10(6) cells-1 for the hydrolysis of ADP, respectively. 5 In conclusion, we report here the cloning and functional expression of a human ecto-ATPase. The study of the biochemical properties and the regulatory mechanisms of ecto-ATPases of defined sequence will be valuable in the definition of their role in nucleotide signalling.

Adenosine Triphosphatases↗
PubMed1999

Serum is more suitable than whole blood for diagnosis of systemic candidiasis by nested PCR.

PCR assays for the diagnosis of systemic candidiasis can be performed either on serum or on whole blood, but results obtained with the two kinds of samples have never been formally compared. Thus we designed a nested PCR assay in which five specific inner pairs of primers were used to amplify specific targets on the rRNA genes of Candida albicans, C. tropicalis, C. parapsilosis, C. krusei, and C. glabrata. In vitro, the lower limit of detection of each nested PCR assay was 1 fg of purified DNA from the corresponding Candida species. In rabbits with candidemia of 120 minutes' duration following intravenous (i.v.) injection of 10(8) CFU of C. albicans, the sensitivities of the PCR in serum and whole blood were not significantly different (93 versus 86%). In other rabbits, injected with only 10(5) CFU of C. albicans, detection of candidemia by culture was possible for only 1 min, whereas DNA could be detected by PCR in whole blood and in serum for 15 and 150 min, respectively. PCR was more often positive in serum than in whole blood in 40 culture-negative samples (27 versus 7%; P < 0.05%). Lastly, experiments with rabbits injected i.v. with 20 or 200 microgram of purified C. albicans DNA showed that PCRs were positive in serum from 30 to at least 120 min after injection, suggesting that the clearance of free DNA is slow. These results suggest that serum is the sample of choice, which should be used preferentially over whole blood for the diagnosis of systemic candidiasis by PCR.

Animals↗
PubMed1999

Patients with thrombocytosis have normal or slightly elevated thrombopoietin levels.

BACKGROUND AND OBJECTIVE: The distinction between clonal and reactive thrombocytoses is a frequent problem and implies different therapeutic options. As thrombopoietin (TPO) is the main regulator of megakaryocytopoiesis and thrombopoiesis, we measured TPO levels in patients with thrombocytosis in an attempt to understand the regulation and potential utility of distinguishing thrombocytoses. DESIGN AND METHODS: Serum TPO levels, platelet counts, mean platelet volume, hemoglobin, erythrocyte sedimentation rate and age were evaluated in 25 patients with clonal thrombocytosis (15 with essential thrombocythemia, 6 with polycythemia vera and 4 with chronic myeloid leukemia) and in 50 patients with reactive thrombocytosis distributed in three groups: 1) patients in post-surgical states; 2) patients with solid tumors; and 3) patients with inflammatory diseases. RESULTS: TPO levels were slightly increased in patients with clonal (135+/-50 pg/mL) and reactive (147+/-58 pg/mL) thrombocytosis compared with controls (121+/-58 pg/mL). Analyzing the different groups, patients with essential thrombocythemia had the lowest TPO levels (120+/-28 pg/mL) and patients with solid tumors the highest levels (162+/-59 pg/mL). Patients with clonal thrombocytosis were older, had higher platelet counts, mean platelet volume and hemoglobin, and lower erythrocyte sedimentation rate than patients with reactive thrombocytosis. INTERPRETATION AND CONCLUSIONS: Minor differences were observed in TPO levels between patients with primary and secondary thrombocytoses. Erythrocyte sedimentation rate, but not TPO levels, may be a useful tool for discriminating both types of thrombocytoses.

Adolescent↗
PubMed1999

Elevated levels of plasmin-alpha2 antiplasmin complexes in unstable angina.

The evidence of elevated levels of several biochemical markers of prothrombotic state in patients with unstable angina suggests that thrombus formation and lysis play a pivotal role in acute coronary syndromes. The clinical syndrome of unstable angina encompasses a variety of clinical presentations of transient episodes of myocardial ischemia. This study was designed to assess plasmin generation in different settings of unstable angina. Evidence of plasmin generation in patients with unstable angina was measured by circulating plasmin-alpha2 antiplasmin complexes (PAP). A second objective was to identify whether PAP levels had a prognostic value to predict outcome. Eighty-five patients admitted to the coronary care unit for unstable angina were classified into three groups. Group A included 26 patients with postinfarction angina; group B comprised 26 patients with new onset angina; and group C included 33 patients with crescendo angina. Mean PAP levels were higher in the three groups compared to healthy controls. A significant correlation was found between levels of PAP and D-dimer, particularly in postinfarction angina (r = 0.6; p <0.0005). This trial adds new insights into the pathophysiology of unstable angina. It demonstrates that plasmin is generated in the different settings of unstable angina but particularly in postinfarction angina patients where a fibrin-rich thrombus is responsible of the symptoms. However, in this series PAP levels do not predict an uneventful outcome neither in the acute phase nor at long term (6 months).

Aged↗
PubMed1999

Homozygotes for prothrombin gene 20210 A allele in a thrombophilic family without clinical manifestations of venous thromboembolism.

BACKGROUND AND OBJECTIVE: A new genetic risk factor for venous thromboembolism has recently been described which involves a G to A transition at position 20210 in the 3' untranslated region of the prothrombin gene. To date, only a few homozygotes for this mutation have been reported and in most of cases, they suffered from thrombotic disease. Here, we describe a pedigree including both heterozygous and homozygous subjects for prothrombin (PT) 20210 A. DESIGN AND METHODS: This family was recruited in 1996 as part of our GAIT (Genetic Analysis of Idiopathic Thrombophilia) project. To qualify for the GAIT study, a pedigree was required to have at least 10 living individuals in three or more generations (i.e. extended pedigree). The pedigrees were selected through probands with idiopathic thrombophilia. A complete set of plasma and DNA determinations related to hemostasis was performed on this family. RESULTS: The plasma studies yielded normal results in all of the individuals. The family members who had a history of thromboembolism were heterozygous carriers of the PT 20210 A variant. In addition, 4 relatives who were heterozygous, and two who were homozygous for this A allele, failed to show clinical manifestations. These two homozygotes were 51 and 19 years old. INTERPRETATION AND CONCLUSIONS: This case exemplifies the complexity of thrombotic disease since individuals homozygous for a mutant gene do not exhibit symptoms while heterozygous individuals often do exhibit the disease. This case suggests that the new genetic risk factor for thrombosis (i.e. PT 20210 A) may not be as strong as most of the previously described genetic risk factors.

3' Untranslated Regions↗
PubMed1998

Ca2+ signals mediated by P2X-type purinoceptors in cultured cerebellar Purkinje cells.

We have studied [Ca2+]i signals elicited by extracellular ATP in cultured cells from postnatal day 7-8 rat cerebellum using single-cell fluorescence microscopy and fura-2. Putative Purkinje cells selected under phase contrast by size and characteristic cytoplasm appearance were uniquely identified by selective labeling with anti-calbindin antibodies. Extracellularly applied ATP (50 microM) evoked fast [Ca2+]i rises revealed by a rapid and transient increase in fura-2 F340/F380 ratio in all Purkinje cells tested, whereas granule cells failed to show a response to ATP. The mean [Ca2+]i increase was approximately 400 nM, comparable to that obtained after glutamate stimulation. The response to ATP was completely abolished by removal of extracellular Ca2+ with EGTA. Conversely, an increased extracellular Mn2+ entry pathway was activated by ATP stimulation. These results indicate that the effect of ATP is mediated by an ionotropic P2X receptor. The action of ATP was mimicked by the analog 2-methylthio-adenosine 5'-triphosphate with similar efficacy but almost half its potency (EC50, 10.6 +/- 0.7 vs 21.7 +/- 1.9 microM). Other purinergic compounds tested, such as adenosine(5')-tetraphospho-(5')adenosine, adenosine(5')pentaphospho-(5')adenosine, adenosine 5'-(alpha, beta-methylene) triphosphate, UTP, and adenosine, were completely inactive in eliciting [Ca2+]i responses. The purinoceptor antagonists suramin and pyridoxalphosphate-6-azophenyl-2', 4'disulphonic acid effectively blocked the responses elicited by ATP. Our results demonstrate for the first time the presence of functional ionotropic P2X purinoceptors in the cerebellar Purkinje cells and indicate that their pharmacology is similar to receptors formed by P2X2 subunit oligomers.

Adenosine Triphosphate↗
PubMed1998

Short-course thrombolysis as the first line of therapy for cardiac valve thrombosis.

OBJECTIVE: To retrospectively evaluate the clinical and echocardiographic criteria of thrombolytic therapy for mechanical heart valve thrombosis. METHODS: Nineteen consecutive patients with 22 instances of prosthetic heart valve thrombosis (14 mitral, 2 aortic, 3 tricuspid, and 3 pulmonary) were treated with short-course thrombolytic therapy as first option of treatment in absence of contraindications. The thrombolytic therapy protocol consisted of streptokinase (1,500,000 IU in 90 minutes) (n = 18) in one (n = 7) or two (n = 11) cycles or recombinant tissue-type plasminogen activator (100 mg in 90 minutes) (n = 4). RESULTS: Overall success was seen in 82%, immediate complete success in 59%, and partial success in 23%. Six patients without total response to thrombolytic therapy underwent surgery, and pannus was observed in 83%. Six patients showed complications: allergy, stroke, transient ischemic attack, coronary embolism, minor bleeding, and one death. At diagnosis, 10 patients evidenced atrial thrombus by transesophageal echocardiography, 3 of whom experienced peripheral embolism during thrombolysis. Four episodes of rethrombosis were observed (16%). The survivorship was 84% with a mean follow-up of 42.6 months. CONCLUSIONS: A short-course of thrombolytic therapy may be considered first-line therapy for prosthetic heart valve thrombosis. The risk of peripheral embolism may be evaluated for the presence of atrial thrombus by transesophageal echocardiography at diagnosis.

Drug Administration Schedule↗
PubMed1998

Inhaled nitric oxide, almitrine infusion, or their coadministration as a treatment of severe hypoxemic focal lung lesions.

BACKGROUND: The partition of pulmonary blood flow between normal and shunting zones is an important determinant of oxygen tension in arterial blood (PaO2). The authors hypothesized that the combination of inhaled nitric oxide (iNO) and almitrine infusion might have additional effects related to their pharmacologic properties to improve PaO2. Such a combination was tested in patients with hypoxia caused by focal lung lesions, distinct from the acute respiratory distress syndrome. METHODS: Fifteen patients with hypoxic focal lung lesions despite optimal therapy were included and successively treated with (1) 5 ppm iNO, (2) low-dose almitrine infusion (5.5 +/- 1.7 microg x kg(-1) min(-1)) during iNO, and (3) almitrine infusion alone (with NO turned off). Then iNO was reintroduced and we studied the effect of the coadministration in reducing the fractional concentration of oxygen in inspired gas (FI(O2)) and positive end-expiratory pressure (PEEP) levels. Changes in blood gases and pulmonary and systemic hemodynamics were measured. RESULTS: Systemic hemodynamic variables remained stable in all protocol conditions. Use of iNO improved arterial oxygenation and decreased intrapulmonary shunt. Almitrine similarly improved PaO2 but increased pulmonary artery pressure and right atrial pressure. Coadministration of iNO and almitrine improved PaO2 compared with each drug alone and with control. All patients responded (that is, they had at least a +30% increase in PaO2) to this coadministration. When the drug combination was continued, FI(O2) and PEEP could be reduced over 8 h. The hospital mortality rate was 33% and unrelated to hypoxia. CONCLUSIONS: In hypoxemic focal lung lesions, iNO or low-dose almitrine markedly improved PaO2 to a similar extent. Furthermore, the coadministration amplified the PaO2 increase at a level that allowed reductions in FI(O2) and PEEP levels.

Administration, Inhalation↗
PubMed1998

Increased risk of venous thrombosis in carriers of natural anticoagulant deficiencies. Results of the family studies of the Spanish Multicenter Study on Thrombophilia (EMET study).

Several studies have demonstrated a higher risk of thrombosis in carriers of anticoagulant deficiencies than in non-deficient individuals from families with thrombophilia. The prevalences in Spain were established in a multicenter study (the EMET study) and all the deficient individuals were invited to recruit all available family members to be screened for the same deficiency in order to establish the risk of thrombosis in deficient individuals. Five-hundred-and-eighty-three individuals from 114 families with natural anticoagulant deficiencies were analysed. Propositi and relatives with a history of thrombosis were asked about the localization and the age at the first episode and whether or not it was spontaneous. Three families with antithrombin deficiency, 35 with protein C, 60 with protein S, four with plasminogen, four with heparin cofactor II, seven with combined deficiencies and one family with dysfibrinogenemia were included in the analysis. The risk of thrombosis was increased for individuals deficient in antithrombin (adjusted odds ratio 21.23; 95% confidence interval 5.71-78.94), protein C (adjusted odds ratio 12.62; 95% confidence interval 4.75-33.51), protein S type I (adjusted odds ratio 19.95; 95% confidence interval 7.40-53.82), protein S type III (adjusted odds ratio 8.11; 95% confidence interval 2.66-21.99) or in protein C plus protein S (adjusted odds ratio 8.99; 95% confidence interval 2.79-28.93), but not for those deficient in plasminogen or heparin cofactor II. The thrombosis-free survival was shortened for deficient individuals in antithrombin (median 30 years), protein C (median 46 years), protein S type-I (median 48 years), protein S type III (median 61 years) and combined protein C and S (median 40 years). In conclusion, individuals carrying anticoagulant deficiencies have an increased risk of thrombosis, especially those with antithrombin, protein C or type I protein S deficiencies.

Adult↗
PubMed1998

Life-threatening primary postpartum hemorrhage: treatment with emergency selective arterial embolization.

PURPOSE: To prospectively evaluate the efficacy and safety of emergency selective arterial embolization in the management of intractable primary postpartum hemorrhage. MATERIALS AND METHODS: Twenty-seven consecutively seen women with life-threatening primary postpartum hemorrhage underwent uterine embolization. In all cases, hemostatic embolization was performed because of intractable hemorrhage that could not be controlled with vaginal packing and administration of uterotonic drugs. The mean hemoglobin level before embolization was 7.48 g/dL +/- 2.39 (74.8 g/L +/- 23.9) (1 standard deviation). Hysterectomy performed in two patients before embolization failed to stop the bleeding. RESULTS: Angiography revealed extravasation in nine patients and spasm of the branches of the internal iliac artery in five. The procedure consisted of embolization of uterine (n = 46), vaginal (n = 5), or ovarian (n = 2) arteries or anterior division of internal iliac arteries (n = 8). Immediate disappearance or dramatic diminution of external bleeding was observed in all cases. Two patients needed repeated embolization the next day. No major complication related to embolization was found. In one patient with placenta accreta, delayed hysterectomy was necessary. Normal menstruation resumed in all women except the two who underwent hysterectomy. One woman became pregnant after embolization. CONCLUSION: Emergency arterial embolization is a safe and effective means of control of primary postpartum hemorrhage. The procedure obviates high-risk surgery and allows maintenance of reproductive ability.

Adult↗
PubMed1998

Skin necrosis at the injection site induced by low-molecular-weight heparin: case report and review.

Heparin-induced skin necrosis at the injection site is a rare adverse effect, more commonly associated with standard heparins than with low-molecular-weight heparins (LMWH) and its mechanism remains unclear. We report a case of LMWH-induced skin necrosis in a female during prophylactic treatment with LMWH after a surgical procedure. Determination of heparin-platelet-factor-4(PF4)-induced antibodies was positive. This case describes the occurrence of LMWH-induced skin necrosis and antibodies to heparin-PF4 complex, suggesting that this effect is more frequent than previously suspected.

Aged↗
PubMed1998

Noninvasive monitoring of cardiac output in critically ill patients using transesophageal Doppler.

Measurement of cardiac output using thermodilution technique in mechanically ventilated patients is associated with significant morbidity. The goal of the present study was to assess the validity of cardiac output measurement using transesophageal Doppler in critically ill patients. Forty-six patients from three different intensive care units underwent 136 paired cardiac output measurements using thermodilution (COTH) and transesophageal Doppler (COTED). In addition, simultaneous suprasternal Doppler and indirect calorimetry (Fick principle) were used to measure cardiac output in 26 patients from one center. A good correlation was found between COTH and COTED (r = 0.95), with a small systematic underestimation (bias = 0.24 L/min) using transesophageal Doppler. The limits of agreement between COTH and COTED were +2 L/min and -1.5 L/min. Variations in cardiac output between two consecutive measures using either transesophageal Doppler or thermodilution techniques were similar in direction and magnitude (bias = 0 L/min; limits of agreement = +/-1.7 L/min). Suprasternal Doppler and indirect calorimetry yielded similar correlations and agreements in the subset of patients in whom they were used. These results confirm that transesophageal Doppler can provide a noninvasive, clinically useful estimate of cardiac output and detect hemodynamic changes in mechanically ventilated, critically ill patients.

Adult↗