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Biomedical subjects

J Pereira

Publications and source records attributed to J Pereira.

At least 127 records · Page 7Linked to original sources

[Allogenic bone marrow transplantation in the treatment of malignant hematologic disease].

We have treated 28 patients (pts) with malignant hematological diseases with allogeneic bone marrow transplantation (BMT). 18 pts had acute lymphoblastic (ALL) and non lymphoblastic leukemia (ANLL), 5 chronic myeloid leukemia (CML), 2 severe aplastic anemia (SAA), 1 myelodisplasia, 1 Fanconi's anemia and 1 advanced Non Hodgkin's lymphoma. All but three received the graft from HLA identical sibling donors. We used conditioning with total body irradiation and chemotherapy (cyclophosphamide, cytarabine and etoposide) in 17 pts and chemotherapy alone in 11. 24 pts had full hematological recovery 18 to 25 days post BMT. 15 pts died after BMT as a consequence of toxicity or early infection (4), graft failure (2), graft versus host disease (4) or relapse (5). Actuarial event free survival for the group with favorable prognosis (SAA, ALL and ANLL in first or second remission and CML in chronic phase) is 57% at 36 months. Allogeneic BMT is an effective and feasible therapeutic procedure for selected patients with hematological malignancies.

Actuarial Analysis↗

[Nutrition and bone mineral density in premenopausal women].

Environmental factors have an important role in osteoporosis. Diet and, in particular, nutrients like calcium, vitamin D or phosphorus were extensively studied as determinants of bone mineral density, but the results remain conflicting and there is no clear evidence for an independent effect of such factors in the bone density of premenopausal women. We studied 66 healthy premenopausal women (20-40 years-old) aiming to relate bone mineral density, as measured in three different sites (distal forearm, lumbar spine and femoral neck) using single X ray and dual energy X-ray absorptiometry, with nutritional intake as estimated by a semi-quantitative food frequency questionnaire. Demographic, anthropometric and other life style variables were also assessed. There was a significant correlation between distal forearm and femoral neck (r = 0.57) or lumbar spine (r = 0.45) bone mineral density. No significant effect of age was observed for distal forearm bone mineral density in these women. In a stepwise multiple linear regression model, evaluating the contribution of all the variables studied, only body mass index (p=0.038) and vitamin A ingestion (p = 0.020) had an independent contribution for the variation in distal forearm bone mineral density. Mean bone mineral density, assessed in the femoral neck (p = 0.003) or the lumbar spine (p = 0.056) was different across tertiles of alcohol ingestion, being higher in non-drinkers. However, among regular drinkers there was a significant positive correlation between alcohol ingestion and femoral neck bone mineral density (Spearman's r = 0.53, p = 0.015). This study shows that the effect of nutrition seems dependent on the anatomical site assessed and that there is a weak correlation between nutritional intake and the actual bone mineral density.

Adult↗

Increased globotriaosylceramide on plasma membranes of synchronized familial dysautonomia cells. Verotoxin binding studies.

Familial dysautonomia is an autosomal recessive genetic disease found almost exclusively among Ashkenazi Jews, characterized by deficits in autonomic, sensory, and central functions. Although the gene has been localized to chromosome 9, the biochemical defect remains elusive. We previously reported an increase in globotriaosylceramide in dysautonomic fibroblasts and lymphoblasts, and unusual fibroblast growth patterns suggesting plasma membrane abnormalities. Globotriaosylceramide is a plasma membrane component, and the natural receptor for verotoxin derived from E. coli. In Vero and HeLa cells, which are susceptible to verotoxin, the expression of globotriaosylceramide on the cell surface is maximal at the G1/S boundary of the cell cycle. Measurement of toxin binding at 0 degrees C at this boundary is indicative of the amount of globotriaosylceramide exposed on the cell surface. Above 0 degrees C, verotoxin enters, and is toxic to, the cell. We analyzed verotoxin-globotriaosylceramide interactions in synchronized FD and normal cells at this boundary. 125I-toxin binding was much more marked to lymphoblasts from patients than from controls. When cells were grown in the presence of verotoxin, at 10(-2)-10(-7) micrograms/mL, 70% of dysautonomic lymphoblasts died, compared to 25% of controls. The CD50 was 10 ng/mL for dysautonomic fibroblasts vs 450 for controls. These results may be exploited to create a biological assay to differentiate between FD and normal cells.

Autonomic Nervous System Diseases↗

A study on the antigenic nature of circulating immune complexes in hemolytic uremic syndrome: no evidence of platelet membrane glycoprotein antigens.

Circulating immune complexes (CIC) have been described in the hemolytic uremic syndrome (HUS) in children. They may represent an epiphenomenon or could be related to the platelet activation and endothelial damage observed in this disease. In an attempt to define this relationship, we investigated the CIC isolated in 17 patients with the classic form of HUS, by means of monoclonal antibodies against platelet surface glycoprotein Ib and IIb-IIIa complex. The negative results obtained do not support the possibility of platelet antigens being constituents of CIC and make an antibody-induced platelet activation in HUS very unlikely.

Antibodies, Monoclonal↗

Long-term remission of neutropenia in Felty's syndrome after a short GM-CSF treatment.

We report a case of Felty's syndrome in which neutropenia was corrected by a short-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 5 micrograms/kg/day s.c. for 14 days). Absolute neutrophil counts rose from 0.1 to 2.2 x 10(9)/l and remained > 1.0 x 10(9)/l 8 weeks after discontinuation of the GM-CSF therapy. A flare-up of arthritis and a decrease in platelet counts were observed.

Adult↗

Bleeding time in preeclampsia.

The association of preeclampsia with thrombocytopenia and prolonged bleeding time is reported. The analysis of bleeding time (Simplate II) and the platelet count (Automatic Coulter Counter) in 41 patients with different grades of preeclampsia is presented. Our results suggest that the decrease in the bleeding time observed in moderate preeclampsia and the increase observed in severe preeclampsia are not mainly dependent on the platelet count.

Adult↗

Accumulation of 5-hydroxytryptamine by aging platelets: studies in a model of suppressed thrombopoiesis in dogs.

Thrombocytopenia was induced in healthy, male mongrel dogs by intramuscular injection of a single dose of estradiol valerate (1 mg/kg). A steady, almost linear decay of the blood platelet count starting about day 6 post-estradiol and attaining a mean value of 14 x 10(3) platelets/microliters one week later was observed. Thrombocytopenia is explained mainly by suppression of thrombocytopoiesis, as established by two independent ways: 1. Megakaryocytes in the bone marrow were markedly reduced. 2. Kinetic studies with 111In labeled autologous platelets revealed a nearly linear decay of the radioactivity and mean survival times within the expected range. The progressive reduction in the platelet count is associated with an increase in the mean age of the platelets still circulating. Following estradiol injection, platelet 5-hydroxytryptamine (5-HT) increased from a basal value of 130 +/- 30 ng/10(8) platelets (platelet count of 351 +/- 53 x 10(3) platelets/microliters) to 343 +/- 100 ng/10(8) platelets eleven days latter, when the platelet count dropped to 32 +/- 18 x 10(3) platelets/microliters. No significant changes in the number or affinity of the 5-HT uptake receptors could be demonstrated in platelets exposed in vitro and in vivo to estradiol. Our results indicate that aging platelets accumulate 5-HT, probably by a sustained exposure to the monoamine in plasma, confirming previous observations based on models in which thrombopenia was induced by immune and mechanical means.

Animals↗

Retrograde percutaneous gastrostomy: a prospective study in 57 children.

We prospectively studied Retrograde Percutaneous Gastrostomy (RPG) in 57 children (age 3 weeks-17 years, 1.7-48 kg) as the feasibility and complications of this technique have not been reported in a large series of children. We used IV sedation (42), oral sedation (4 neonates), general anaesthesia or local anaesthesia only. The retrograde approach for gastrostomy or gastrojejunostomy catheter placement is described. Catheter placement was unsuccessful in only one child, due to the presence of marked hepatosplenomegaly. Catheters were successfully placed in all the other 56 children. In one of these, catheter misplacement occurred due to retraction of the stomach from the anterior abdominal wall during its insertion. This was recognized during the procedure. The catheter was removed and reinserted on the same occasion. One catheter was accidentally pulled out after six days and was subsequently replaced. Two children had mild, local abdominal tenderness and fever for up to 48 hours but post procedure septicemia or significant infection were not encountered. All children benefitted from gastrostomy feeding and gained weight.

Adolescent↗

Studies on the delineation of the antigenic determinants of chicken riboflavin carrier protein (cRCP). Identification of a determinant in the region 10-24 of the protein.

As riboflavin carrier proteins play a critical role in the maintenance of pregnancy, studies on the immunology of these proteins have become very relevant. This paper describes our attempts to identify the sequential antigenic determinants of chicken riboflavin carrier protein (cRCP). Potential surface oriented regions of cRCP were identified by constructing acrophilicity and hydrophilicity profiles of the protein. Of the three regions identified, the pentadecapeptide 10-24 of cRCP forms the subject of the present study. The pentadecapeptide amide was synthesized by solid phase synthesis using Fmoc chemistry. Immunization of rabbits with the peptide-diphtheria toxoid conjugate elicited high titres of the antipeptide antibodies, revealing the high immunogenicity of the peptide. The antipeptide antibodies bound to both cRCP and reduced carboxymethylated RCP (RCM-RCP). Antisera to RCM-RCP showed significant binding to the peptide showing thereby that the region 10-24 of cRCP is perhaps one of the major epitopes of RCM-RCP. Thus, the studies have resulted in the identification of the region 10-24 as an antigenic determinant of cRCP.

Amino Acid Sequence↗

Improved presentation of antigenic sites in enzyme-linked immunosorbent assay: antigenicity of reduced and carboxymethylated riboflavin carrier protein.

Disulphide reduced and carboxymethylated riboflavin carrier protein (RCM-RCP), an unfolded derivative of chicken RCP, does not bind riboflavin and there is a drastic reduction in its ability to interact with antiserum to cRCP. Antibodies to RCM-RCP are directed against sequential epitopes(s). On radioiodination of RCM-RCP, a maximum of 30-50% binding at dilution of 1:500 was obtained with rabbit antibodies RCM-RCP [n = 5]. However, high titer antibodies was obtained when radioiodinated RCM-RCP was immobilized on ELISA microtiter plates suggesting that immobilization of RCM-RCP leads to either preservation of antigenic sites or improved presentation of the antigenic determinants. An avidin-biotin system was utilized to develop an ELISA.

Animals↗

[Diagnosis of von Willebrand's disease subtypes by the analysis of multimeric composition of plasma von Willebrand factor].

The accurate diagnosis of the type of von Willebrand's disease (vWD) is important for a better understanding of its pathogenesis and for adequate treatment decision. We assessed the usefulness of the analysis of the multimeric composition of von Willebrand factor (vWF) in the diagnosis of vWD variants. vWF is purified by gel filtration and polyclonal, heterologous antibodies are raised in rabbits, which are immunopurified and radioiodinated. These are used to reveal, by autoradiography, the bands of vWF of various molecular weights separated by electrophoresis in agarose gels. This procedure reveals that 74 (80%) out of 92 patients with vWD suffer the classic type (I) of the disease, 6 (6.5%) type as IIA, 6 (6.5%) as IIB and 6 (6.5%) as III. The test is necessary for the correct classification of the patients, but is complex, laborious and expensive; it should be performed in patients with high probability of vWD or after the generic diagnosis of vWD has been made.

Adolescent↗

Total sialic acid in human and canine platelets does not change with the platelet age.

Total platelet sialic acid (SA) was measured in three experimental conditions: (1) human and canine platelet density subpopulations obtained by centrifugation in arabinogalactan gradients, (2) circulating canine platelets during recovery from experimental immune and mechanical thrombocytopenias, and (3) platelets obtained from a patient with chronic immune thrombocytopenic purpura before and after splenectomy. The density of human and canine platelets is, in part, determined by their age. We found no significant differences in total SA between high-density (HD) and low-density (LD) platelets (9.32 +/- 2.0 vs. 9.55 +/- 1.3 micrograms/mg of platelet protein in dogs and 9.02 +/- 2.3 vs. 9.10 +/- 2.9 micrograms/mg in humans). In the human and canine thrombocytopenic models, the entrance of new platelets from the bone marrow is followed by their aging in the circulation. In these models, no significant changes in total SA content were detected in sequential measurements during the recovery of the thrombocytopenia. Accordingly, we conclude that total SA in human and canine platelets is unrelated to their age in circulation. These results do not support the notion that the loss of SA from membrane glycoproteins determines the recognition and removal of platelets from the circulation.

Animals↗

Body water compartments in patients with obstructive jaundice.

To elucidate the pathogenesis of renal dysfunction associated with obstructive jaundice, body water compartments were measured using a multi-isotope dilution technique in ten patients with biliary tract obstruction and in ten control subjects matched for age, sex, weight, height and body surface area. Expressed as a fraction of body-weight, total body water was reduced in jaundiced patients (41.8 versus 46.2 per cent, P less than 0.02). Extracellular water volume was also reduced in patients with jaundice (20.3 versus 24.3 per cent, P less than 0.003) owing to a reduction of the interstitial space (16.1 versus 19.5 per cent, P less than 0.004) and, to a lesser degree, of the plasma volume (4.2 versus 4.8 per cent, P = 0.1). There was a close correlation in jaundiced patients between plasma volume and the creatinine clearance rate (r2 = 0.56, P less than 0.02) and between plasma volume and extracellular volume (r2 = 0.77, P less than 0.0001). Extracellular volume in such patients also correlated with the percentage weight loss (r2 = 0.42, P = 0.04). Obstructive jaundice is associated with a contracted extracellular water compartment, although extracellular water, as a percentage of body-weight, increased in proportion to the body-weight lost. Reduction of the interstitial volume and a marginally reduced plasma volume may be determinant factors in the pathogenesis of the renal and haemodynamic disturbances observed in patients with biliary tract obstruction.

Aged↗

HM-PAO spect in head trauma.

Single Photon Emission Computed Tomography (SPECT) after intravenous administration of Technetium-99m hexamethylpropylene-amine oxime (Tc-99m HM-PAO) makes possible the evaluation of cerebral perfusion. We have been assessing the diagnostic accuracy of SPECT in some groups of head trauma patients: the preliminary results of this study are presented. Fourteen patients have been selected, all of them showing some kind of focal neurological deficit; the Computed Tomography (CT) and Nuclear Magnetic Resonance (NMR) were normal, or showed lesions that could not be responsible for the neurological deficits. In all of the patients Tc-99m HM-PAO SPECT has been performed, showing changes in cerebral perfusion in areas correlated with the abnormalities elicited on clinical examination. These results show that Tc-99m HM-PAO SPECT is a better technique than CT or NMR in demonstrating the organic basis of some neurological deficits observed after head trauma.

Adolescent↗