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Biomedical subjects

E Rocha

Publications and source records attributed to E Rocha.

At least 91 records · Page 5Linked to original sources

[Diltiazem 180 mg in delayed release formulation in mild and moderate arterial hypertension].

INTRODUCTION: Having acknowledge the need to treat arterial Hypertension concomitantly effective, safe and easy to comply with. These issues are the mainstay for a good adherence to a treatment that is long. AIM: This clinical trial addresses the efficacy and safety of an extended release tablet of 180 mg of diltiazem, once daily, to treat mild to moderate hypertension. POPULATION AND METHODS: Forty-five patients with mild to moderate hypertension were included in a multicentric, open trial consisting of three periods: washout (one week), placebo (one week) and a treatment period of four weeks with 180 mg slow-release tablets of diltiazem. Arterial Blood Pressure (BP) was measured through ambulatory blood pressure monitoring (ABPM) at the end of the first, second and sixth weeks. The therapeutic response was evaluated in terms of decrease in mmHg and in terms of systolic and diastolic loads. Treatment was considered successful when there was a drop in the medium diastolic BP to 90 mmHg or less and/or a decrease of at least 10 mmHg. RESULTS: Twenty-three patients completed the trial. There was a significant decrease (p < 0.0001) in the medium diastolic and systolic 24-hour BP values. The efficacy parameters were met in 62.5% of the patients, nonetheless there was a drop of at least 5 mmHg in 82.6%. There was a statistically more significant response during the diurnal versus the nocturnal periods, according to both criteria. CONCLUSION: Diltiazem, 180 mg extended-release tablet taken one daily, proved to be effective, over 24 hours, in controlling Hypertension in 62.5% of the enrolled patients while decreasing the medium diastolic BP by at least 5 mmHg in 82.5%.

Adult↗

[Inhibitor of the extrinsic pathway of coagulation and cytokines in patients with sepsis].

PURPOSE: To analyse the possible correlation between the plasma levels of the extrinsic pathway inhibitor (TFPI) in patients with infection along with two cytokines mediating in the action of bacterial endotoxin on the vascular endothelium, namely, tumour factor (TNF) and interleukin-1 (IL-1). PATIENTS AND METHODS: Twenty-five patients with infection, none of them showing septic shock or disseminated intravascular coagulation, were studied. Plasma TFPI concentration was assessed by a chromogenic substrate technique; TNF was determined with immunoradiometric methods and IL-1 was estimated with ELISA. The results were compared with those of a group of 25 healthy subjects matched for age and sex. RESULTS: Positive blood cultures were found in 15 of the 25 patients (60%), 12 due to gram-negative and 3 to gram-positive germs. A significant increase of TFPI (p < 0.004), TNF and IL-1 (p < 0.001) was found in infection patients with respect to the control subjects. No significant correlation between TFPI and TNF or IL-1 was found. CONCLUSION: Increased TFPI, unrelated to cytokines, is present in patients with sepsis.

Adolescent↗

Endotoxin-induced intravascular coagulation in rabbits: effect of tissue plasminogen activator vs urokinase of PAI generation, fibrin deposits and mortality.

We have evaluated the effect of plasminogen activators (t-PA and urokinase) on an experimental model of disseminated intravascular coagulation (DIC) in rabbits by injection of 20 micrograms/kg/h of E. coli lipopolysaccharide during 6 h t-PA (0.2 mg/kg and 0.7 mg/kg), urokinase (3000 U/kg/h) and saline (control) were given simultaneously with endotoxin. Results indicated that urokinase and low dose of t-PA significantly reduced the increase of plasminogen activator inhibitor (PAI) activity observed 2 h after endotoxin (p < 0.001). High t-PA dose also diminished the PAI levels at 6 h (p < 0.001). A significant reduction of fibrin deposits in kidneys was observed din both t-PA treated groups as compared with findings in the group of rabbits infused with saline solution (p < 0.005), whereas urokinase had no significant effect on the extent of fibrin deposition. Finally, the mortality rate in the control group (70%) was reduced to 50% in rabbits receiving high doses of t-PA. In conclusion, treatment with t-PA resulted in reduced PAI generation, fibrin deposits and mortality in endotoxin-treated rabbits.

Animals↗

Cytogenetic data in 41 patients with multiple myeloma. Karyotype and other clinical parameters.

Cytogenetic data of 41 patients diagnosed with multiple myeloma (MM) are reported. In all samples, cytogenetic studies were made of short-term and B-cell-stimulated culture: 20 cases (48.8%) showed chromosome abnormalities; 14 karyotypes were hypo- or pseudodiploid, and six were hyperdiploid. The most frequent numerical changes affected chromosomes 7, 11, 5 (gains), 14, 20, and Y (losses). Chromosome structural rearrangements of 22q were noted in six patients. Other and recurrent cytogenetic abnormalities were changes involving chromosomes 1, 14, and 17. A significant relation was observed between presence of chromosome abnormalities and the following hematologic parameters: clinical stage III (p = 0.0212), bone marrow (BM) plasma cell infiltration greater than 30% (p = 0.0379), presence of bone lesions (p = 0.0051), and beta 2-microglobulin levels greater than 4,000 md/dl (p = 0.0194).

Adult↗

Chronic administration of lithium chloride increases immunodetectable glial fibrillary acidic protein in the rat hippocampus.

We studied the effect of treating rats with lithium salts on the content and in vitro phosphorylation rate of the astrocyte cell marker, glial fibrillary acidic protein (GFAP), in brain slices. Rats were fed a diet incorporating lithium chloride until the concentration of Li+ in serum reached 0.6-1.2 mM, a range similar to that achieved in clinical practice. Hippocampal tissue was analyzed for immunoreactive GFAP by a dot assay, and slices of hippocampus and caudate nucleus were labeled with [32P]phosphate to determine the in vitro rate of phosphorylation of GFAP. Compared with controls, the level of immunoreactive GFAP in the hippocampus from lithium-treated rats was increased 34%, and GFAP in hippocampal slices incorporated 39% more 32P. This effect of lithium was apparently not confined to the hippocampus because the in vitro rate of phosphorylation of GFAP in caudate slices was also increased in the treated rats.

Animals↗

Randomized study of aprotinin and DDAVP to reduce postoperative bleeding after cardiopulmonary bypass surgery.

BACKGROUND: Patients on cardiopulmonary bypass (CPB) have an increased susceptibility to postoperative bleeding. Previous reports using desmopressin acetate (DDAVP) for the prevention of postoperative bleeding have given contradictory results, whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery. This randomized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB. METHODS AND RESULTS: One hundred nine of 122 eligible patients were randomized to four different groups: Group A (n = 28) received aprotinin starting with a bolus of 2 x 10(6) KIU followed by a continuous infusion of 0.5 x 10(6) KIU/h until the end of surgery; group B (n = 25) received of DDAVP 0.3 micrograms/kg i.v. on completion of CPB; group C (n = 28) received two doses of DDAVP, the first as in group B and an additional dose 6 hours after surgery; group D (n = 28) received no treatment. There was a marked reduction of postoperative blood loss either at 12 hours (P < .01) or 72 hours (P < .02) in the aprotinin group compared with all other groups, whereas no significant effect was observed in either of the two DDAVP regimens. A significant reduction in the amount of blood used was observed only in the aprotinin group (P < .01). Of the plasma fibrinolytic components assayed, there was a significant reduction of the fibrin degradation product generation in the aprotinin group (P < .001), whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group. No side effects related to the study drugs were observed in any patient. CONCLUSIONS: Aprotinin inhibited fibrinolysis; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB. Neither one nor two doses of DDAVP had a beneficial effect. Aprotinin offers a better alternative than DDAVP in the prevention of bleeding after CPB.

Aprotinin↗

Incidence of non-Hodgkin's lymphoma in patients treated for Hodgkin's disease.

The purpose of this study was to evaluate the incidence of non-Hodgkin's lymphoma (NHL) as a second tumor in patients treated for Hodgkin's disease (HD), as well as to establish the role of different variables in its appearance. Between January 1973 and June 1988, 101 patients with HD were treated according to the stage, with chemotherapy and/or radiotherapy. Complete remission was obtained in 87 patients. Five patients developed secondary NHL between the 77th and 124th month of complete remission. The median follow up was 73 months (range 3-227 months). The incidence of second NHL in our series was, 0%, 4.6% (CI 0-11%) and 17% (CI 4-32%) at 5, 10 and 15 years respectively. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, splenectomy, histology, stage and treatment modality) showed that the only statistically significant variable was the treatment received (p < 0.01). Cumulative incidence of NHL at 15 years, ranged from 0% for patients treated with radiotherapy or chemotherapy alone to 39.6% for those who received combined therapy (p = 0.002). We can conclude that the use of chemotherapy plus radiotherapy for treatment of HD increases the risk for the development of second NHL.

Adolescent↗

The liver of the brown trout, Salmo trutta fario: a light and electron microscope study.

A qualitative study by light and electron microscopy was undertaken on the liver of the brown trout, Salmo trutta fario. Vessels and bile ducts were observed to be scattered without any apparent order within the parenchyma. Venous profiles appeared either isolated or included in 'venous-arteriolar tracts' (VAT) and 'venous-biliary-arteriolar tracts' (VBAT). Bile ducts also appeared either isolated or in groups which often included an arteriole. The parenchyma was organised in tubules of hepatocytes encircling biliary passages radially. Those cells were uninucleate and contained large cytoplasmic areas of rough endoplasmic reticulum; lipid droplets and dense bodies sometimes also occupied a considerable portion of the cytoplasm. Microvilli extended from hepatocytes into biliary passages and towards the space of Disse. Other cell types encountered comprised biliary epithelial cells, macrophages (including melanin laden cells), fat-storing cells and endothelial cells. The biliary tree was formed sequentially by intra- and intercellular canaliculi, preductules, ductules and ducts. Canaliculi without microvilli are described for the first time in fishes. Structural differences between the brown trout and other fishes were noted. In contradistinction to other fishes, in brown trout the triads (i.e. the VBAT) are not just occasional structures; also, they probably transmit portal veins. Our observations support the concept of a tubular arrangement of hepatocytes in fish. The possibility that the axis of the tubule may be a sinusoid instead of a biliary passage is questioned. Homology between, on one hand, the segment formed by preductules and ductules and, on the other, the canal of Hering of mammals is defended. It is concluded that among salmonids notable interspecific differences do not seem to exist.

Animals↗

[Comparative multicenter study of a rabbit high-sensitivity thromboplastin and a recombinant thromboplastin with synthetic phospholipids].

PURPOSE: The purpose of the present study was to compare the results obtained with a human recombinant thromboplastin (Innovin, Baxter) (IN) and a high-sensitivity rabbit brain reagent (Thromboplastin IS, Baxter) (IS), on the performance of prothrombin time (PT) test and the functional assay of factors included in the extrinsic coagulation system, in order to establish possible differences on imprecision, diagnostic accuracy and sensitivity to the oral anticoagulant defect, between the two products. MATERIAL AND METHODS: Six Spanish hospital took part in the study. Plasma samples from 221 healthy subjects, 100 patients with severe liver disease, 27 with dysfibrinogenaemia, 10 with lupus anticoagulant and from 13 individuals propositus and their relatives with congenital deficiencies of the extrinsic coagulation pathway, and their relatives were studied; 188 patients stabilized on oral anticoagulant therapy and 82 on heparin therapy were also included. The in vitro effect of heparin was tested by addition of increasing amounts of heparin (0.3 to 10.0 IU/mL) to aliquots of normal plasma. RESULTS: Both in the intra-assay and in the inter-assay imprecision study, a better coefficient of variation was obtained with IN when the PT was performed on abnormal samples. Prothrombin time ratio from patients with liver disease had significantly higher values with IS. On the contrary, IN had a higher sensitivity in samples from patients with dysfibrinogenaemia or from those stabilized on oral anticoagulant therapy. In showed a very low sensitivity to heparin at concentrations corresponding to the therapeutic range. CONCLUSIONS: The results of this field study indicate that IN, compared with a high-sensitivity rabbit brain thromboplastin, is a suitable reagent for PT determination in normal subjects, patients with liver disease or with congenital deficiencies of clotting factors. It shows a higher sensitivity in cases of dysfibrinogenaemia and in patients on oral anticoagulant therapy. In addition, the recombinant reagent had better reproducibility when the PT was performed on abnormal samples, and it was hardly affected by heparin within the therapeutic range.

Afibrinogenemia↗

[Functional characterization of a monoclonal antibody which interferes with the binding of t-PA to fibrin].

PURPOSE: Development of monoclonal antibodies capable of inhibiting the specific binding of t-PA to fibrin. MATERIAL AND METHODS: After immunization of Balb/c mice with recombinant t-PA (rt-PA) we selected the monoclonal antibody MA3B5 by its ability to inhibit the binding of t-PA to fibrin, and the MA2C1 devoid of this property. The influence of such antibodies was evaluated on fibrin plates, amidolytic assays and clot lysis assays. Furthermore, their interference with the activator bound to fibrin was assayed with a spectrophotometric solid phase assay (SOFIA). RESULTS: The results showed that MA3B5 totally inhibited the t-PA induced fibrinolytic activity on fibrin plates, reduced amidolytic activity by 86.5% and inhibited the clot lysis induced by t-PA in a dynamic system. In contrast, the MA2C1 showed no inhibition. By assessing the binding of t-PA to fibrin with the SOFIA assay we could demonstrate that only the MA3B5 reduced significantly (up to 90% with 100 micrograms/mL of antibody) the amount of t-PA bound to fibrin surface. CONCLUSION: We have purified and characterized a monoclonal antibody which specifically blocks the fibrin binding site of t-PA.

Animals↗

Thrombin-antithrombin complexes and prothrombin fragment 1+2 in aorto-coronary bypass surgery: relation to graft occlusion.

Graft thrombotic occlusion is a common complication in patients undergoing aorto-coronary bypass surgery. Clotting activation seems to contribute to the thrombotic event. We have determined the plasma concentrations of two hemostatic markers, thrombin-antithrombin (TAT) complexes and prothrombin fragment 1+2 (F 1+2) in 100 patients undergoing revascularization procedures of whom 81 underwent shunt angiography. Angiographically proven graft occlusion was present in 19 patients (23.5%). A significant increase of both parameters was observed immediately after surgery and on postoperative days 1 and 5 (p < 0.001), although a relationship to graft occlusion could not be demonstrated. However, the preoperative TAT concentration was higher in patients developing graft occlusion (p < 0.01). We conclude that there is a marked clotting activation in patients undergoing aorto-coronary bypass surgery, as demonstrated by elevated TAT and F 1+2 concentrations. Preoperative TAT values can be good markers of early graft occlusion.

Aged↗

Heterogeneity and death of Purkinje cells of rat neocerebellum (Crus I and Crus II): hypothetic mechanisms based on qualitative and quantitative microscopical data.

The morphological changes that take place with ageing in the soma of what we call clear Purkinje cells (CP cells) are examined by light and electron microscopy. Besides the very obvious lipofuscin accumulation, another kind of space consuming structures become greater in number and complexity, i.e., the occurrence of very pleomorphic degenerating focal zones. Apart from CP cells, dark Purkinje cells (DP cells) indeed appear in increasing numbers with ageing; one subtype (DP-1 cells) has medium dark density revealing dumbbell-shaped mitochondria, ring-shaped Golgi apparatus and lamellated bodies; the other subtype (DP-2 cells) has very dark density presenting pycnotic nuclei with complete nucleolar regression and degenerating mitochondria, but with well developed Nissl bodies and Golgi apparatus. The possibility of DP cells not being technical artifacts is discussed. Quantitative studies are also carried out in Purkinje cell somata: mean volume, surface-to-volume ratio, absolute volume occupied with lipofuscin dense bodies as well as the linear density (number per mm) and percentage of CP and DP cells out of the total population of Purkinje cells. Statistically significant linear trends with age are found for absolute volume of lipofuscin in CP cells and for the linear densities and percentages of either CP or DP cells. The concatenation of qualitative and quantitative data suggests that Purkinje cells of Crus I and Crus II undergo an age-related fall-out. Some clear Purkinje cells may become DP-1 cells and others DP-2 cells. The former reveal signs of slow cellular damage; the latter are suggestively very damaged or even dead cells probably on account of having exceeded the critical threshold of the surface-to-volume ratio leading to asphyxia; indeed, their stout structure does not match slow damage.

Animals↗