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Biomedical subjects

B P Simões

Publications and source records attributed to B P Simões.

13 recordsLinked to original sources
PubMed2006

Frontline therapy with early intensification and autologous stem cell transplantation versus conventional chemotherapy in unselected high-risk, aggressive non-Hodgkin's lymphoma patients: a prospective randomized GEMOH report.

This prospective multicenter randomized trial compares conventional with early intensification with high-dose sequential chemotherapy (HDS) and autologous stem cell transplantation (ASCT) as frontline therapy in high-risk non-Hodgkin lymphomas (NHL). Newly diagnosed patients with aggressive high-risk [intermediate-high (HI) and high-risk (HR)] NHL according to the international prognosis index (IPI) were randomized to receive 12-week VACOP-B (arm A, 27 patients) or 6-week VACOP-B followed by HDS and ASCT (arm B, 29 patients). Complete remission rate was 52% in arm A and 55% in B. Nine patients (16%) died early due to progression. According to intention-to-treat, with a median follow-up of 23 months, the 5-year actuarial overall survival, progression-free survival and disease-free survival in arms A and B were 47 and 40% (p = nonsignificant), 47 and 30% (p = nonsignificant), and 97 and 47% (p = 0.02), respectively. Abbreviated chemotherapy followed by intensification with HDS-ASCT does not seem to be superior to conventional chemotherapy in HI/HR aggressive NHL.

Adolescent↗
PubMed2002

A randomized, multicenter study of G-CSF starting on day +1 vs day +5 after autologous peripheral blood progenitor cell transplantation.

In order to assess the effect of delaying G-CSF administration after autologous peripheral blood progenitor cell (PBPC) transplantation on the duration of neutropenia, 87 patients were randomized to receive G-CSF 5 microg/kg/day starting on day +1 (n = 45) or +5 (n = 42) following PBPC transplantation, until recovery of the neutrophils. The duration of neutropenia (<0.5 x 10(9)/l) was shorter in the day +1 group (7 vs 8 days; P = 0.02), especially in patients receiving melphalan 200 mg/m(2) and CD34(+) cell doses >3.0 x 10(6)/kg. These patients had a later onset of neutropenia after transplant. There were no differences in time to neutrophil and platelet engraftment, or in the incidence of fever and documentation of infection. Although the duration of antibiotic therapy (7 vs 10.5 days; P = 0.01) and time to hospital discharge (13 vs 15 days; P = 0.02) were shorter in the day +1 group, these differences could not be predicted by the day of G-CSF initiation in multivariate analysis. Starting G-CSF on day +1 does not result in faster neutrophil engraftment but in later onset and consequently, slightly shorter duration of neutropenia in patients who receive melphalan 200 mg/m(2) and CD34(+) cell doses >3.0 x 10(6)/kg.

Adolescent↗
PubMed2001

The methylenetetrahydrofolate reductase C677T gene polymorphism decreases the risk of childhood acute lymphocytic leukaemia.

We have determined the prevalence of methylenetetrahydrofolate reductase (MTHFR) mutations C677T and A1298C in 71 children (< or = 15 years) with acute lymphoblastic leukaemia (ALL) and in 71 control subjects. Odds ratio (OR) for ALL linked to MTHFR C677T was 0.4 (95% CI 0.2-0.8); for heterozygotes it was 0.5 (95% CI 0.2-0.9) and for homozygotes it was 0.3 (95%CI 0.09-0.8). MTHFR A1298C yielded an overall OR for ALL of 1.3 (95% CI: 0.7-2.6); for heterozygotes it was 1.3 (95% CI: 0.7-7.6) and for homozygotes it was 2.8 (95% CI 0.5-15.6). In conclusion, MTHFR C677T was linked to a significant 2.4-fold decreased risk of developing childhood ALL, whereas MTHFR A1298C did not significantly affect the risk of ALL in our population.

Adolescent↗
PubMed1996

Racial heterogeneity of DNA polymorphisms linked to the A and the O alleles of the ABO blood group gene.

Except for subgroup A2 and minor A, O and B alleles (Ax, O2 and B(A)), which occur at low frequencies in the population, the major ABO alleles are considered to be homogeneous entities. The present study is the first demonstration of an extensive variability linked to the more common alleles of the blood A and O genes by digestion of the genomic DNA with different restriction enzymes and hybridization with a probe generated by PCR amplification of a segment of the last exon of the glycosyltransferase gene. For group A in Whites, two or three-allele fragment length polymorphisms (RFLP) were demonstrated by Hinc II, Taq I and Hinf I; for group O two to five-allele RFLP were detected in Blacks, Whites and Amerindians with restriction enzymes Hinc II, Bgl I, Kpn I, Taq I and Hinf I. These polymorphisms probably originated by single-base changes, although a length variation due to variable number of tandem repeats cannot be ruled out for some. Allelic association between the different restriction sites permitted the identification of seven O allele haplotypes in Blacks, and two in Whites and Indians. Three different haplotypes were identified for group A in Whites. The greater heterogeneity of the O allele among the Blacks as compared with Whites and Indians is similar to that observed for other gene systems. The polymorphisms of the histoblood group ABH antigen genes seem a useful tool for population genetics, phylogenetics and evolution studies.

ABO Blood-Group System↗
PubMed1995

Relative frequencies of the two O alleles of the histo-blood ABH system in different racial groups.

O blood group results from the absence of glycosyltransferase activity, which is due most commonly to a single nucleotide deletion in the glycosyltransferase gene. A second type of O allele resulting from three nucleotide substitutions in the glycosyltransferase gene had its frequency recently determined in a Danish population. However, its frequency among different human populations is not known. The frequencies of the two types of O alleles were determined by DNA analysis of the glycosyltransferase gene of group O individuals of three racial groups (Caucasians, blacks and Amerindians). The mean frequency of carriers of the three-base mutation group O gene among blacks and Caucasians is 4.7%; the mutation was not observed among 100 Amerindian chromosomes. The data reveal the relative frequencies of O alleles in different racial groups, and demonstrate that the origin of this variant predates racial divergence, since it is found equally among blacks and whites.

ABO Blood-Group System↗
PubMed1995

Splenic function in acute leukemia.

Spleen function was evaluated in 36 patients with acute leukemia by enumeration of pitted erythrocytes and analysis of clearance from circulation of heat-damaged 99mTc-labelled erythrocytes (HDE). At diagnosis, the mean percentage of pitted erythrocytes was significantly higher in the patient group (4.04 +/- 7.19%) than in the control group (0.41 +/- 0.35%; p < 0.01), suggesting the occurrence of a splenic hypofunction in a high proportion of the patients. Accordingly, the clearance of HDE showed a pattern of splenic hypofunction in 4 out of 7 patients, based on reduced values for the parameters C20 (overall clearing function of the spleen), K (the rate constant of HDE irreversibly trapped) and K/K1 + K (the fraction of HDE entering the spleen undergoing permanent removal). After successful treatment, the pit counts decreased in all reassessed patients, returning to normal values in 10 out of 12 patients with high pit counts at diagnosis. Additionally, two patients with normal pit counts at diagnosis presented borderline results for the parameters C20 and K, which may suggest a slight splenic hyperactivity in these patients. These results demonstrate, for the first time, the presence of functional spleen abnormalities in patients with acute leukemia.

Acute Disease↗
PubMed1994

Large DNA inversions, deletions, and TaqI site mutations in severe haemophilia A.

Large DNA inversions caused by an intrachromosomal recombination between homologous regions located in intron 22 and 5' of the factor VIII gene have recently been identified in patients with severe haemophilia A. To evaluate better the prevalence of this large inversion and to estimate the overall sensitivity of the Southern blot/hybridization method we analysed the factor VIII gene of 49 unrelated patients with severe haemophilia A. All patients were screened for the inversion mutation, TaqI site mutations, and deletions. Mutations were identified in 31 (63%) patients, and comprised 24 large inversions, 4 partial deletions, and 3 point mutations. Three different haplotypes were characterised in the patients presenting the inversion mutation, confirming its independent origin. Two novel deletions are reported: a large one spanning from intron 14 to intron 22 and a deletion of 86 bp comprising the 3' region of exon 1 and 39-41 bp of intron 1. DNA sequencing of the deletion junction showed no significant homology between normal 5' and 3' sequences around the breakpoints. A novel missense mutation is also reported: CGA-->GGA, Arg-2209 to Gly. These results confirm that the inversion mutation is the most common cause of severe haemophilia A and indicate that the Southern blot/hybridization assay should be used as the first method for screening of mutations in severe haemophilia A.

Base Sequence↗
PubMed1994

Molecular bases of the ABO blood groups of Indians from the Brazilian Amazon region.

Phenotype studies of ABO blood groups in most Amerindian populations revealed the exclusive presence of group O. Since group O is the result of the absence of glycosyltransferase activity, its molecular bases may be heterogeneous. We carried out ABO blood group genotyping by analysis of DNA of 30 Indians from 2 Amazonian tribes (Yanomami and Arara), and compared the findings with other populations (Caucasians and Blacks). Two segments of the glycosyltransferase gene were amplified by PCR and digested with KpnI or AluI to detect deletion or base change at positions 258 and 700, respectively. For all subjects, the gene basis of blood group O is the deletion of a single nucleotide at position 258 of the glycosyltransferase A gene, similar to that observed in Caucasoids and Negroids. DNA sequencing of limited regions of the gene supports this conclusion. This finding does not exclude, however, that a heterogeneity of the O allele may be revealed by a more extensive analysis.

ABO Blood-Group System↗
PubMed1994

[Reagudization of Chagas myocarditis inducing exclusive right ventricular failure].

Woman, 42 years-old, receiving immunosuppressive therapy for a lymphoma, presented reagudization of Chagas' disease, from its indeterminate phase. Intense inflammatory visceral aggression, due to extensive intracellular proliferation of the Trypanosoma cruzi, was the likely mechanism for acute myocarditis leading to severe right ventricular failure. Antiparasite chemotherapy was effective in the control of visceral involvement and for the remission of cardiac failure. The clinical course in this case is compatible with the hypothesis of early right ventricular damage in Chagas' disease.

Adult↗
PubMed1992

Malignant T gamma/delta lymphoproliferative disease with natural killer lytic activity.

A 17-year-old girl presented with a lymphoproliferative disease involving the bone marrow, peripheral blood, and liver associated with reactive hyperplasia of the spleen. Neoplastic cells were atypical medium-sized lymphoblasts with convoluted nuclei and nucleoli without features of large granular lymphocytes (LGL). The phenotype was CD3+ CD4- CD8-, TCR alpha/beta-, TCR gamma/delta+, delta TCS1-, and CD16+, and these cells exhibited spontaneous natural killer (NK) activity. DNA analysis showed rearrangement of the TCR gamma gene but not of TCR beta or of Ig mu genes. This unusual lymphoproliferative disease may represent the neoplastic expansion of a minor subset of normal T gamma/delta cells with NK activity.

Adolescent↗