Search PubMed⌕ Search

Biomedical subjects

M Villa

Publications and source records attributed to M Villa.

At least 73 records · Page 4Linked to original sources
PubMed1997

Non-tunneled catheters for the collection and transplantation of peripheral blood stem cells in children.

We analyzed the use of non-tunneled (polyurethane, double lumen) central venous catheters (CVCs) for the collection, conditioning, transplantation and immediate post-transplantation periods in 56 children with various malignant diseases. A total of 71 leukaphereses were performed, with a mean of 1.2 apheresis per patient, following administration of granulocyte colony-stimulating factor (G-CSF) using a continuous flow blood cell separator (Cobe Spectra). The mean TBV (total blood volume) processed was 4.5 +/- 1.2 s.d. (range 2.4-7). The mean flow rate was 30.6 ml/min and the duration of a single apheresis was 327 +/- 84 s.d. (range 175-511 min). The mean purities and efficacies of collections were 77.38 +/- s.d. (range 42-100) and 42.78 +/- s.d. (range 24-80), respectively. The mean numbers of mononuclear cells (MNC) and CD34+ cells collected were 9.3 +/- 6.9 s.d. x 10(8)/kg (range 2-49) and 6.2 +/- 7.2 s.d. x 10(6)/kg (range 1-42), respectively. We observed the following complications during catheter insertion for collection: pneumothorax (1.7%), mechanical dysfunction (3.5%) that resolved with thrombolytic therapy. Complications during conditioning, transplantation and immediate post-transplantation periods were entry site infection in five patients (8.92%), catheter-related infection in two (3.57%) and catheter-related sepsis in three (5.35%). Our results indicate that the collection of PBSC with non-tunneled catheters is safe, effective and dis associated with a low incidence of complications.

Adolescent↗
PubMed1997

Allogeneic peripheral blood progenitor cell (PBPC) transplantation in children with haematological malignancies.

We report on five children with haematological malignancies who underwent allogeneic peripheral blood progenitor cell (PBPC) transplantation. PBPC were harvested from HLA-identical sibling donors after G-CSF (10 micrograms/kg/d s.c.) mobilization. Aphereses were carried out on day 5 after G-CSF using a Cobe Spectra blood cell separator. All PBPC allografts were cryopreserved before transplantation. The median of CD34+ cells and CD3+ cells infused were 14.1 x 10(6)/kg recipient body weight (range 4.92-22.3) and 2.40 x 10(8)/kg recipient body weight (range 0.54 4.82), respectively. Engraftment occurred in all cases. The median time to a neutrophil count > 0.5 x 10(9)/l and a platelet count > 20 x 10(9)/l were 15 and 14 d, respectively. The incidence of severe acute graft-versus-host disease was 20%. These data suggest that allogeneic PBPC transplantation might be an alternative to bone marrow transplantation in children.

Child↗
PubMed1997

Acute renal failure in pregnancy.

From 1976 to 1994, 57 women were referred to the Centro de Nefrología, Montevideo, with obstetric acute renal failure (ARF). The main causes were hypertensive disorders such as preeclampsia (PE) in 27, acute pyelonephritis of pregnancy (APN) in 26, and idiopathic postpartum renal failure in 3. Severe preeclampsia superimposed on chronic hypertension and acute pyelonephritis of pregnancy complicated by sepsis accounted for more than 50% of the cases of ARF. Chronic renal failure developed in 6 patients: 2 had bilateral renal cortical necrosis, 1 had malignant nephrosclerosis, and 3 had idiopathic postpartum renal failure. Maternal mortality related to ARF was low in this group of patients (less than 2%). In contrast, perinatal mortality was strikingly high (40%).

Acute Kidney Injury↗
PubMed1996

Type 1 cytokine production and low prevalence of viral isolation correlate with long-term nonprogression in HIV infection.

Cytokine production, prevalence of viral isolation, and surface marker expression of peripheral blood mononuclear cells (PBMCs) were analyzed in HIV+ individuals with different patterns of disease progression to establish correlations between these parameters. Thus, mitogen-stimulated in vitro production of interferon gamma (IFN-gamma) and interleukin 2 (IL-2) (type 1 cytokines), and of IL-4 and IL-10 (type 2 cytokines) as well as prevalence of viral isolation were evaluated in 26 HIV+ long-term nonprogressors (LTNPs), in 28 HIV+ patients with progressive HIV infection (PI), and in 24 HIV-seronegative controls (HCs). Surface expression of activation and nonactivation markers was also analyzed in a group of these donors. We report that (1) IL-2 and IFN-gamma production is reduced and IL-4 and IL-10 production is increased in PI patients compared to HCs and LTNPs; (2) prevalence of HIV isolation is lower in LTNPs compared to PI, and the primary viral isolates in LTNPs show a slow/low (S/L) phenotype; and (3) the elevated production of type 2 cytokines is paralleled by an increase in CD57+CD4+CD7- lymphocytes. Thus, whereas a high IL-2, high IFN-gamma/low IL-4, low IL-10 cytokine production pattern is present in HC and in LTNP HIV+, progression of HIV infection is associated with a low IL-2 low IFN-gamma/high IL-4, high IL-10 cytokine profile; increased prevalence of HIV isolation; and an augmented percentage of CD57+CD4+CD7- lymphocytes. These findings further confirm that a dominant type 1 cytokine profile together with reduced prevalence of virus isolation is associated with lack of progression in HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Short-term crocidolite inhalation studies in mice: validation of an inhalation chamber.

A nose-only inhalation chamber is described: this chamber being computer automated has been particularly designed for mice on which it was validated using a crocidolite aerosol at a nominal concentration of 13.6 mg/m3, 6 h/day during 5 days. A month later the mice showed typical inflammatory bronchoalveolar liquids with many polynucleated or activated macrophages and asbestos bodies. The burden of crocidolite fibers ranged from 345,000 to 1,300,000 fibers per mg of dried lung. This study demonstrates that during the month that followed a short-term mice exposure to crocidolite fibers, the inflammatory response was still persistent. These toxicological endpoints validate the nose-only inhalation chamber to be useful for common or transgenic mice.

Administration, Inhalation↗
PubMed1996

Idiotypic study of a bispecific thyroglobulin and thyroperoxidase monoclonal antibody.

We have previously established that thyroperoxidase (TPO), a major thyroid antigen involved in autoimmune thyroid diseases, interacts with an idiotype present on human and mouse antibodies directed to thryoglobulin (TG), another thyroid autoantigen. In order to characterize the TPO-reactive idiotype, we selected a TG monoclonal antibody (mAb J7 B49.15) which bound to TPO and cross-reacted with human bispecific TG and TPO autoantibodies (TGPO aAb) for both TG and TPO binding. The TPO-reactive structure of the mAb J7 B49.15 was present on the F(ab')2, located next to the TG binding site and dependent on the association of the heavy and light chains. We found that mAb J7 B49.15 shared a TPO-reactive idiotypic structure with TG mAb from the same cluster of TG reactivity. All the mAb from this cluster were directed to an immunodominant region of TG, recognized by TG aAb. Natural anti-idiotypes from pooled normal human IgG used as a therapeutic intravenous preparation inhibited the TPO binding to mAb J7 B49.15. By homologous immunization in BALB/c mice, mAb J7 B49.15 induced an antiserum with both TG and TPO reactivities. Whereas TG reactivity decreased as early as day 14 post-immunization, TPO reactivity remained at a plateau value from day 21 to day 42. The TG and TPO reactive antisera were shown to inhibit the binding of mAb J7 B49.15 to TG and TPO, respectively. We concluded that mAb J7 B49.15 reacted with TPO through an interspecies idiotype which appeared conformational and related to the epitopic specificity of the mAb. Interestingly, this idiotype would carry the internal image of a TG structure able to induce, in homologous system, a TG antibody response followed by a TPO response without the need of any immunizing antigen.

Animals↗
PubMed1996

Collection and transplantation of peripheral blood progenitor cells mobilized by G-CSF alone in children with malignancies.

Results of collection and transplantation of peripheral blood progenitor cells (PBPC) mobilized by G-CSF in 31 children with different malignancies were analysed. A total of 43 aphereses were performed, following administration of granulocyte colony-stimulating factor (G-CSF), using a continuous flow blood cell separator (Cobe Spectra) through a central venous catheter. For patients weighing 0.5 x 10(9)/l and a platelet count of 20 x 10(9)/l without platelet support were 9.5 and 18, respectively. The number of CD34+ cells infused correlated highly with engraftment kinetics. The extra-medullary toxicity was low and manageable.

Adolescent↗
PubMed1996

Characterization of agonist-induced down-regulation of NMDA receptors in cerebellar granule cell cultures.

Exposure of cerebellar granule cells to NMDA in culture at 5 days in vitro, when cells are not yet vulnerable to NMDA, evoked a pronounced reduction in NMDA receptor activity, measured by NMDA-induced 45Ca2+ influx, and counteracted the normal developmental increase in NMDA receptors. The effect was concentration and time dependent, the half-maximal effect being reached at about 45 microM and by 4-5 h. The decrease in NMDA receptor function was accompanied by a significant reduction in the protein level of the obligatory NMDA receptor subunit (NR) NR1. Both parameters remained at a low level as long as the agonist was present. However, receptor down-regulation was reversible, as receptor protein levels and NMDA responses were restored to control values upon NMDA removal, this process requiring protein synthesis. NMDA treatment also elicited a decrease in NR1, NR2A, and NR2B subunit messenger RNA (mRNA) levels. However, in comparison with NMDA receptor proteins, the decrease was faster, and NMDA receptor mRNA content recovered to control levels within 24 h in spite of the presence of NMDA. Concerning the mechanisms of agonist-induced regulation of NMDA receptor expression, it seems that protein kinase C-mediated protein phosphorylation is not involved, whereas inhibition of Ca2+/calmodulin-dependent kinase II/IV by KN-62 does depress NMDA receptor expression even in the absence of NMDA.

Animals↗
PubMed1996

Developmental and regional expression of NMDA receptor subtypes containing the NR2D subunit in rat brain.

The regional and developmental expression of NMDA receptors containing the NR2D subunit was analyzed on the level of the subunit mRNA and protein in rat brain. RNase protection experiments indicated that among two proposed splice variants of the NR2D subunit, only the NR2D-2 subunit is expressed. The regional distribution of the NR2D subunit protein was visualized with a newly developed NR2D-2 subunit-specific antiserum on brain sections using the histoblot technique. In adult brain, NR2D immunoreactivity was mainly restricted to diencephalic, mesencephalic, and brainstem structures. During postnatal development, the NR2D subunit was detected transiently in certain regions, such as the ventrobasal complex of the thalamus, hippocampus, inferior colliculus, and brainstem reticular formation, suggesting that NR2D subunit-containing receptors play a role in these brain areas only during development. The level of NR2D subunit mRNA and protein decreased during late postnatal development. However, significant levels of NR2D subunit mRNA and protein were present in adulthood, in particular, in the globus pallidus, thalamus, subthalamic nuclei, and superior colliculus. These results indicate a functional relevance for NMDA receptors containing the NR2D subunit in the developing and adult brain, although its expression in the adult brain is less prominent and restricted to a few brain areas.

Aging↗
PubMed1996

Mosaicism for the fragile X syndrome full mutation and deletions within the CGG repeat of the FMR1 gene.

The main mutation responsible for the fragile X syndrome is the expansion of an untranslated CGG repeat in the first exon of the FMR1 gene, associated with the hypermethylation of the proximal CpG island and the CGG repeat region, and repression of transcription of FMR1. Fragile X syndrome mosaicism has been described as the coexistence of the full mutation and the permutation. We present here two cases of mosaicism for the full mutation in the FMR1 gene and deletions involving the CGG repeat region. In one case the deletion removed 113 bp proximal to the CGG repeat and part of the repeat itself, leaving 30 pure repeats, and representing 17% of lymphocytes of the patient. The 5' breakpoint of this deletion falls outside the putative hotspot for deletions in the CGG region of FMR1. In the second case the deleted region only involved the CGG sequence (leaving 15 pure repeats), with normal sequences flanking the repeat; this deleted ("normal") FMR1 was estimated to be in about 31% of blood lymphocytes. This second case can be considered a true regression of the CGG FMR1 expansion to a normal sized allele, although in mosaic form.

Adolescent↗
PubMed1996

Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.

PURPOSE: To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs). MATERIALS AND METHODS: Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest. RESULTS: The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001). CONCLUSION: Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.

Adolescent↗
PubMed1996

Non-tunneled catheters in children undergoing bone marrow transplantation.

We analyzed the use of non-tunneled (polyurethane double lumen) central venous catheters (CVCs) in 62 children undergoing bone marrow transplantation. The catheters were inserted in the Critical Care Unit without surgery or general anesthesia. The complications were pneumothorax in two patients and hemopneumothorax in two other patients (6.06%), entry site infection in six patients (9.6%), catheter-related infection in eight patients (12.9%) and catheter-related sepsis in nine patients (14.5%). The catheters were removed upon completion of therapy in 46 patients (74.1%), death in seven patients (11.3%) and in nine cases (14.5%) for infection. Despite the complications specific to non-tunneled catheter insertion, we believe this is indicated for patients during conditioning, transplantation and immediate post-transplantation periods.

Adolescent↗
PubMed1996

Large-volume leukapheresis for peripheral blood stem cell collection in children: a simplified single-apheresis approach.

Large volume leukapheresis (LVL) defined as the processing of greater than three volumes of blood in a single session for peripheral blood stem cell (PBSC) collection was performed in 27 children, aged from 1 to 15 years, with various malignancies. Harvesting of PBSC was started after 4 days of cytokine (G-CSF 12 micrograms/kg s.c.) alone. With the exception of two cases the rest (92.5%) needed only a single apheresis to yield the minimum number of cells required for transplantation. No consistent side-effects were observed and the LVL were well tolerated by children. An average of 7.6 x 10(8) MNC/kg, 6.1 x 10(6)/kg CD34+ and 2.1 x 10(4)/kg CFU-GM were harvested. To date, 19 patients have been transplanted after myeloablative treatment and sustained engraftment was achieved in all cases. LVL can be safely and easily performed in children allowing adequate PBSC collection for transplantation with prompt hematological engraftment.

Adolescent↗
PubMed1996

Allogeneic peripheral blood progenitor cell (PBPC) transplantation in children.

The use of peripheral blood as a source of hematopoietic precursors is an alternative to the bone marrow in allogeneic transplantation. Although pediatric allogeneic PBPC experience is limited, there is no reason to believe that the outcome and benefit with PBPC should be different than adults. We describe our initial experience in two children who received PBPC allogeneic transplantation in whom the donors were mobilized with filgrastim. Hematopoietic recovery was achieved on days 14 and 16, and the patients did not develop severe GVHD.

Adolescent↗
PubMed1996

Pediatric experience with autologous peripheral blood progenitor cell transplantation: influence of CD34+ cell dose in engraftment kinetics.

The aim of this study was to analyze factors affecting mobilization and engraftment in 40 children undergoing autologous peripheral blood progenitor cell transplantation for different malignancies: 19 patients with haematological malignancies and 21 patients with solid tumors. Patients received 4-5 days of rhG-CSF (12 micrograms/kg/day) subcutaneously. Apheresis was performed by continuous flow blood cell separation beginning on the fifth day of rhG-CSF. For patients weighing < or = 25 kg, the extracorporeal line was primed with irradiated red blood cells. After myeloablative conditioning regimens, patients were grafted with 7.21 +/- 7.8 x 10(6)/kg CD34+ cells. Days to achieve an absolute neutrophil count > 0.5 x 10(9)/1 and a platelet count > 20 x 10(9)/1 without platelet support were 9.50 +/- 1.2 (range 7-13) and 18.1 +/- 8.3 (range 9-37), respectively. The number of CD34+ cells infused was highly correlated with engraftment kinetics (P = 0.0001). The patient's body weight and the number of previous chemotherapy courses had a negative influence on CD34+ cells collected.

Adolescent↗
PubMed1996

Chimerism after allogeneic hematopoietic cell transplantation in childhood acute lymphoblastic leukemia.

Leukemic relapse after allogeneic bone marrow transplantation or allogeneic peripheral blood progenitor cell transplantation arises normally from residual malignant host hematopoiesis. The lack of specific tumor markers in acute lymphoblastic leukemia presents a problem for detection of residual disease post-infusion. In the present prospective study, we used PCR amplification of variable numbers of tandem repeat genetic regions for close follow-up of chimeric status in order to try to distinguish those patients at high risk of relapse. We found that chimeric status evolution was different between the long-term surviving patients and relapsed patients. The former showed either donor chimerism (DC) or transient mixed chimerism (tMC), while the latter always showed a recipient-growing MC (r.gMC). In addition, we found that complete substitution of hematopoiesis was achieved better with radiation-containing regimens, and that chronic graft-versus-host disease never appeared in MC patients. We conclude that very close follow-up of serial samples can facilitate the early detection of those leukemic children with a poor outcome after hematopoietic cell transplantation.

Adolescent↗