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Biomedical subjects

E Rocha

Publications and source records attributed to E Rocha.

At least 127 records · Page 7Linked to original sources

Autologous bone marrow transplantation in 22 adult patients with lymphoblastic lymphoma responsive to conventional dose chemotherapy.

In order to clarify the role of autologous bone marrow transplantation in adult lymphoblastic lymphoma (LBL) patients we have conducted a retrospective multi-institutional Spanish survey. Twenty-two adult patients, 20 males, two females, age 14-52 years (median 25.5) with LBL were treated with high-dose chemoradiotherapy and autologous bone marrow support. Fourteen cases were transplanted in first complete remission (CR1) and eight with other chemosensitive status (four later CR, two partial remissions and two sensitive relapses). From the 14 cases transplanted in CR1, four had previous bone marrow involvement and one meningeal infiltration; eight cases were Ann-Arbor stage IV and fulfilled accepted high-risk criteria for relapse. The conditioning regimen consisted of cyclophosphamide (60 mg/kg x 2) and total body irradiation (9-12 Gy) in 16 cases and high dose chemotherapy in six. The procedure-related mortality was 9% (7% in CR1 patients). The actuarial 2-year overall survival for CR1 patients was 85% at a median follow-up of 19 months. Disease-free survival (DFS) was 77%. In patients with less favourable disease status the 2-year overall and DFS were 73% and 50% respectively. In this study the DFS in CR1 patients was not influenced by bone marrow involvement or high-risk criteria predictive for relapse. These results support the effectiveness of this procedure, mainly for patients in CR1.

Adolescent↗

[Effect of heparin and/or antithrombin III in a model of disseminated intravascular coagulation induced by endotoxin in rabbits].

Disseminated intravascular coagulation (DIC) was induced in 84 rabbits by intravenous infusion of 20 micrograms/kg/h of endotoxin during 6 hours. The following treatments were administered simultaneously with endotoxin: heparin, 5, 10 and 20 UI/kg/h, antithrombin III (AT III), 10, 20 and 40 U/kg/h or as a 240 U/kg bolus dose, and heparin (10 UI/kg/h) plus AT III (20 U/kg/h). Blood samples were taken before endotoxin and 2 and 6 hours after endotoxin to perform screening coagulation assays, factors V, VIII and XII, AT III, fibrin monomers and fibrinogen degradation products. All treatments were able to modify some of the parameters related to DIC, but only AT III bolus dose and heparin plus AT III significantly reduced fibrin deposition in kidneys (p less than 0.05). All the therapeutic schedules significantly diminished the mortality rate. We conclude that AT III bolus dose and heparin plus AT III are useful in the treatment of endotoxin-induced intravascular coagulation in rabbits.

Animals↗

[Cytogenetic marker del(12p) in a case of acute myeloid leukemia M4 with eosinophilia and inv(16)].

A 35-year-old Spanish female having acute myelomonocytic leukaemia with marrow eosinophilia is reported. The karyotype revealed the specific chromosomal abnormality associated with this disorder, inv(16), and a less-specific myelodysplastic cytogenetic marker, del(12p). We have reviewed the published cases in order to elucidate the possible significance of presenting a 12p deletion (nonrandomly associated with chronic myelomonocytic leukaemia) together with other chromosomal rearrangements.

Adult↗

Thrombin activation and increased fibrinolysis in patients with chronic liver disease.

The respective roles of intravascular coagulation (DIC) and fibrinolysis were assessed in severe chronic liver disease by measuring thrombin-antithrombin (TAT) complexes, tissue-type plasminogen activator antigen (tPA Ag) and fibrinogen and fibrin degradation products (FgDP and FbDP respectively) in 66 patients with liver disease caused by cirrhosis (n = 34) or chronic hepatitis (n = 32) as compared to findings in a control group (n = 30). There was a significant increase of TAT complexes (P less than 0.01), tPA Ag (P less than 0.002), FDP and FbDP (P less than 0.001) in patients as compared to controls. FbDP increase was more evident in patients with cirrhosis than in those with hepatitis (P less than 0.01). Significant correlations between these parameters with some liver function tests were also demonstrated. Thus, in patients with severe liver disease, an increased thrombin activity, as demonstrated by high TAT levels; followed by hyperfibrinolysis suggest that a low grade DIC may occur.

Adult↗

Antigenic and genetic variation in influenza A (H1N1) virus isolates recovered from a persistently infected immunodeficient child.

Antigenic and genetic variations have been analyzed in eight consecutive isolates recovered from a child with severe combined immunodeficiency syndrome persistently infected with naturally acquired type A (H1N1) influenza virus over a 10-month period. Hemagglutination inhibition reactions and T1 oligonucleotide fingerprinting demonstrated that these viruses were related to strains causing outbreaks in the United States at that time (1983 to 1984) but that antigenic and genetic differences between consecutive isolates could be detected. This variation between isolates was examined further by sequencing the RNAs encoding the HA1 region of the hemagglutinin (HA) and the nucleoprotein (NP) in five of the consecutive isolates. Multiple point mutations were detected in both genes, and a deletion of one amino acid was detected in the HA. Depending on the isolates compared, 5.8 x 10(-3) to 17 x 10(-3) substitutions per nucleotide site per year were detected in the RNAs encoding the HA1, and 3.5 x 10(-3) to 24 x 10(-3) substitutions per nucleotide site per year were detected in the NP gene. Fifty-four percent of the base changes in the HA1 and 73% in the NP led to amino acid substitutions. A progressive accumulation of mutations over time was not observed, suggesting that the genetic diversity of these viruses may best be interpreted as the result of shifts in the population equilibrium (quasi-species) of replicating variant genomes.

Amino Acid Sequence↗

Intra- and postoperative fibrinolysis in patients undergoing cardiopulmonary bypass surgery.

The influence of cardiopulmonary bypass (CPB) on fibrinolytic activity was assessed in 100 patients with valvular heart disease or atrial septal defects. Euglobulin fibrinolytic activity (EFA), tissue type plasminogen activator (t-PA) activity, plasminogen activator inhibitor 1 (PAI-1) activity, plasminogen, alpha 2-antiplasmin (alpha 2-AP), fibrinogen degradation products (FDP), and D-dimer were measured pre-, intra-, and postoperatively. There were significant increases in EFA and t-PA activity (p less than 0.002), and decreases in plasminogen and alpha 2-AP (p less than 0.0001) intraoperatively with respect to baseline values. t-PA activity decreased significantly after surgery (p less than 0.002), whereas PAI-1 activity showed a marked increase shortly after operation and on postoperative day 1 (p less than 0.0001). FDP and D-dimer levels were significantly increased both intra- and postoperatively, the latter showing higher values (p less than 0.01 and p less than 0.0001, respectively). This study shows that there is an activation of the fibrinolytic system, as a result of the increased activation of plasminogen and decreased levels of plasmin inhibitors, during CPB surgery followed by a postoperative fibrinolytic shutdown.

Adult↗

Types 1 and 2 plasminogen activator inhibitor and tumor necrosis factor alpha in patients with sepsis.

We have determined the plasma concentrations of types 1 and 2 of plasminogen activator inhibitor (PAI-1 and PAI-2), tumor necrosis factor (TNF-alpha) and endotoxin in 47 patients with bacterial infection (22 patients presented with positive blood cultures). Results were compared with those observed in 30 healthy subjects. There was a significant increase in PAI-1 and TNF-alpha in patients as compared to controls (p less than 0.0001), whereas no differences for PAI-2 were observed. PAI-1 and TNF-alpha were significantly higher in 18 patients with gram-negative bacteremia as compared to all other patients (p less than 0.0001). However, no correlation between the analyzed parameters and either endotoxin or clinical outcome was observed. We conclude that there is an increase of PAI-1 and TNF-alpha in patients with sepsis, which is not related to the endotoxin concentration. Our results suggest that PAI-1, but not PAI-2, is the main plasminogen activator inhibitor in human sepsis.

Adolescent↗

Effects of undernutrition during suckling on phosphoryl serine levels in nuclear and synaptosomal proteins from cerebral cortex of rats.

The effect of undernutrition during suckling on phosphoryl serine levels was investigated in rats. Young rats were undernourished by suckling their lactating mothers fed an 8% (by weight) protein diet. Mothers of normal rats were fed a 25% protein diet. After weaning (21 d), normal and undernourished rats were fed a 25% protein diet until 90-120 d of age. Previously we observed that undernutrition during suckling decreases the levels of phosphoryl serine in nuclear proteins from the whole brain of adult rats. In this paper we report more specifically on the effect of undernutrition during this period on the levels of phosphoryl serine in nuclear and synaptosomal proteins from the cerebral cortex of young and nutritionally rehabilitated adult rats. In young, undernourished rats the levels of phosphoryl serine in nuclear proteins were significantly lower (28%) than those in control animals. This alteration persisted in nutritionally rehabilitated adult rats. Serine and protein levels in cerebral cortex were the same in all groups. No alteration in the levels of phosphoryl serine in the synaptosomal fraction was observed.

Animals↗

Fibrinogen and fibrin degradation products in patients undergoing open-heart surgery.

We have determined fibrinogen and fibrin degradation products (FgDP and FbDP respectively) by an ELISA method using specific monoclonal antibodies in 100 patients undergoing cardiopulmonary bypass (CPB) for valvular heart disease and in 60 patients undergoing aorto-coronary bypass surgery. Blood samples were taken pre-operatively and on post-operative days 1 and 5. Post-operative evolution was similar in both patient groups, with a significant increase in FgDP on post-operative days 1 and 5 with respect to baseline value (P less than 0.01). FbDP were also significantly higher on post-operative days 1 and 5 (P less than 0.001), especially the day after surgery in patients with valvular disease as compared with coronary patients (P less than 0.01). Our results indicate that fibrinolysis is more important than fibrinogenolysis after open-heart surgery, which may have pathophysiological implications.

Cardiopulmonary Bypass↗

Fibrinogen Oviedo I. A new Spanish dysfibrinogenaemia.

An abnormal fibrinogen was discovered in the plasma of a clinically asymptomatic woman. Laboratory evaluation of five members of the affected family showed low fibrinogen values in kinetic assays whereas the fibrinogen levels, tested by immunological procedures were normal. The patient's plasma had an inhibitory effect on the thrombin time of normal plasma. The calcium ions totally corrected the thrombin and reptilase times. Either low or high ionic strength prolonged the thrombin time of the proposita's purified fibrinogen. Kinetic analysis of clotting by monitoring transmission at 350 nm showed abnormally slow clotting with thrombin and reptilase. Assays were preformed in whole plasma as well as in purified fibrinogen. A delay in the rate of polymerization was evident when purified patient monomers were compared with those of normals. Immunoelectrophoretic, chromatofocusing, and isoelectrofusing experiments detected neither structural nor immunological abnormalities of fibrinogen. The rate of release of fibrinopeptide A by thrombin, measured by a specific immunoenzymatic method was also normal. HPLC analysis showed normal liberation of fibrinopeptides after prolonged thrombin action. Cross-linking of fibrin by factor XIII and lysis of fibrinogen by plasmin were normal. In view of these results, the defect of this dysfibrinogenemia, designated as Fibrinogen Oviedo I, probably could be due to conformational modifications in the D section of the molecule.

Adult↗

Effect of heparin and/or antithrombin III on the generation of endotoxin-induced plasminogen activator inhibitor.

It has been experimentally shown that endotoxin induces a significant increase in the blood levels of a plasminogen activator inhibitor (PAI). We evaluated the effect of different doses of heparin (5 to 20 IU kg-1 h-1), antithrombin III (10 to 40 U kg-1 h-1 and 240 U/kg as bolus) and of a combination of the two on: 1) the elevation of PAI activity, 2) fibrin deposition in kidneys and 3) mortality in rabbits infused with E. coli lipopolysaccharide. Our results show that heparin plus AT III is able to significantly reduce the generation of endotoxin-induced PAI activity in rabbits' circulation. Low dose of heparin and a bolus injection of AT III both cause a decrease in the generation of PAI at 2 but not at 6 hours of endotoxin infusion. Moreover, fibrin deposits in kidneys of animals receiving heparin plus AT III or a bolus injection of AT III were significantly reduced as compared to control rabbits. The association between low levels of PAI and decreased fibrin deposits is strengthened by the significant correlation (p less than 0.05) found between these two parameters. Finally, the plasma levels of PAI activity at 2 and 6 hours of endotoxin infusion in surviving animals were lower than those observed in animals that died within 2 hours after the end of treatment. We conclude that heparin plus AT III partially prevents the endotoxin-induced generation of PAI activity which seems to correlate with the reduced presence of fibrin deposits in kidneys and with a reduced mortality.

Animals↗

Clotting activation and impairment of fibrinolysis in malignancy.

Different coagulation and fibrinolysis parameters were investigated in 149 patients with metastatic and non-metastatic tumours and results were compared with those obtained in a healthy population. Results showed a significant increase of thrombin-antithrombin complexes, fibrinopeptide A (FPA) and fibrin monomers in the group of patients (p less than 0.001). There was also a significant prolongation of euglobulin lysis time (p less than 0.005) and an increase of plasminogen activator inhibitor activity (p less than 0.0001), fibrinogen degradation products (p less than 0.001), and D-dimer (p less than 0.05) in the group of patients as compared to controls; FPA levels were also increased in patients with metastases (p less than 0.005). This study demonstrates clotting activation, at the level of fibrinogen to fibrin conversion, and impairment of fibrinolysis in patients with malignancy.

Adolescent↗