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Biomedical subjects

M Villa

Publications and source records attributed to M Villa.

At least 55 records · Page 3Linked to original sources
PubMed1999

Single-strand conformation polymorphism analysis in the FMR1 gene.

The fragile X syndrome is due to an expansion of the CGG trinucleotide repeat in the FMR1 gene and hypermethylation of its 5' upstream CpG island in about 95% of the cases. The remaining 5% of cases correspond to other molecular alterations in FMR1 gene such as partial or complete deletions, or point mutations within the coding sequence. We selected 31 patients with clinical manifestations of fragile X syndrome, scoring 16 or more in Hagerman's checklist, but without the CGG expansion. We performed single-strand conformation polymorphism analysis using a nonradioactive technique (silver staining) and we detected six anomalous migrations that, by sequence analysis, corresponded to six nucleotide changes. We screened two different populations (control and fragile X) for these changes, and concluded that they correspond to five new polymorphisms within the FMR1 gene and to one possible synonymous mutation.

Fragile X Messenger Ribonucleoprotein 1↗
PubMed1999

Evolution strategy optimization for adiabatic pulses in MRI.

We propose a new type of adiabatic pulses for uniform inversion of the magnetization in magnetic resonance imaging. We produced these pulses with an evolution strategy optimization, by which the search of the "best solution" has been made more efficient than by deterministic algorithms. The pulse parametrization takes into account an "offset-independent adiabaticity condition," which guarantees insensitivity to RF inhomogeneities. The RF pulse power (both peak and mean) contributes to the cost to be minimized, as well as the error function does: in this way we obtain solutions that require lower energy than the well-known hyperbolic-secant pulse, with no loss of quality in the response profile.

Algorithms↗
PubMed1999

Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis?

Eighty nephrotic adults with focal segmental glomerulosclerosis (FSGS) and plasma creatinine lower than 3 mg/dL were given corticosteroids (53 patients) or immunosuppressive agents (27 patients) for a median of 16 and 75 weeks, respectively. Forty-two patients responded with complete remission (29 patients, 36%) or partial remission (13 patients, 16%). Twenty-six patients who did not respond were treated again. Two patients obtained complete remission and 13 partial remission. The probability of remission was associated with treatment with corticosteroids (P = 0.0001; RR, 3. 93; 95% CI, 2.00 to 7.72), absence of arterial hypertension (P = 0. 0023; RR, 2.59; 95% CI, 1.41 to 4.79), and a percentage of hyaline glomeruli lower than 5% (P = 0.0152; RR, 2.04; 95% CI, 1.15 to 3.64). The probability of being alive at 110 months without doubling of plasma creatinine was 69%. The risk of renal insufficiency was correlated with mesangial proliferation (P = 0.0025; RR, 5.50; 95% CI, 1.82 to 16.60) and with interstitial fibrosis (P = 0.0231; RR, 4. 44; 95% CI, 1.23 to 16.08) at initial biopsy. Considering partial or complete remission as a time-dependent variable, only the lack of remission (P = 0.0027; RR, 7.23; 95% CI, 1.98 to 26.33) and mesangial proliferation (P = 0.0069; RR, 4.59; 95% CI, 1.52 to 13. 88) were correlated with renal failure. Major side effects were observed in 11 patients (5 infections, 1 peptic ulcer, 2 diabetes, 3 neoplasias). This study shows that 70% of nephrotic adults with FSGS may obtain complete or partial remission and maintain stable renal function for about 10 years when given a prolonged therapy with corticosteroids or immunosuppressive drugs.

Adrenal Cortex Hormones↗
PubMed1999

Stem cell component therapy: supplementation of unmanipulated marrow with CD34 enriched peripheral blood stem cells.

Eleven patients with hematologic malignancies and two with aplastic anemia were treated using unmanipulated marrow and immunoselected CD34+ blood cells. Donors began G-CSF (10 microg/kg) injections 1 day after undergoing bone marrow harvest. Blood stem cells were collected on day 5 of G-CSF. Peripheral blood lymphocytes were depleted via CD34-positive selection. If, after marrow and blood harvest, less than 2.0 x 10(6) CD34 cells/kg were mobilized, leukapheresis was repeated on day 6. Median time to an absolute neutrophil count greater than 500 microl was day 10; transfusion-independent platelet count greater than 20,000/microl was day 13; average hospital discharge was day 14; and average inpatient hospital charges were 101,870 US dollars. Acute GVHD grade II occurred in five of 13 patients. No patient developed grade III or IV acute GVHD. At a median follow-up of 10 months, no patient has developed extensive chronic GVHD. Allografts of unmanipulated bone marrow supplemented with G-CSF-mobilized and CD34 immunoselected blood cells may prevent an increased risk of GVHD while preserving the rapid engraftment kinetics of peripheral blood. Supplementation of marrow with CD34 enriched blood cells appears to result in rapid engraftment, early hospital discharge, lower inpatient charges, decreased regimen-related toxicity, and no apparent increase in GVHD.

Adult↗
PubMed1999

Immunohistochemical detection of breast cancer cells in paired peripheral blood progenitor cell specimens collected after cytokine or cytokine and myelosuppressive chemotherapy.

Mobilized peripheral blood progenitor cells (PBPC) from 30 patients with advanced breast cancer were studied for the presence of tumor cell contamination using a highly sensitive immunohistochemical technique with the capacity to detect one tumor cell in one million mononuclear cells. Aliquots of PBPC were obtained after 4 days of G-CSF and/or GM-CSF and again during G-CSF-stimulated recovery from myelosuppressive doses of cyclophosphamide. The overall incidence of tumor cell contamination was 23%, occurring in PBPC specimens from seven of 30 patients. All four cases in which tumor cells were detected after mobilization with cytokine alone also had tumor cells detected in PBPCs collected following chemotherapy and G-CSF. There were three cases in which malignant contamination was detected only in the specimens collected after cyclophosphamide. There was a greater frequency of tumor cell contamination in aphereses performed during G-CSF-stimulated recovery from cyclophosphamide than in collections primed by cytokine alone (13% vs 23%; P = 0.08), although this did not reach statistical significance. This trend suggests that collection of PBPC during cytokine-stimulated recovery from myelosuppressive chemotherapy may be associated with a greater risk of contamination with malignant cells than apheresis during mobilization with cytokines in the steady state.

Adult↗
PubMed1999

New adiabatic inversion pulses for magnetic resonance imaging.

We present a comparison between our strategy of computing new adiabatic pulses and the best results given so far in the literature by Rosenfeld and co-workers. Our technique has been described elsewhere and is based upon a simple physical idea (the adiabatic factor is offset independent) and an evolution strategy algorithm which stochastically searches for a 'solution' with optimal inversion profile and power characteristics. As expected for all adiabatic pulses, the inversion profiles are similar for our solutions and those of the literature. On the other hand, some of our pulses offer a substantial reduction of peak and average power relative to the solutions of Rosenfeld. We discuss the properties of the families of analytical functions, where, in our opinion, it is convenient to search for a pulse shape with optimal inversion profile and power characteristics.

Algorithms↗
PubMed1999

In vivo quantitative lipidic map of brown adipose tissue by chemical shift imaging at 4.7 Tesla.

In the present paper, chemical shift imaging techniques are applied to quantitative in vivo evaluation of fat and water content in interscapular brown adipose tissue (BAT). The experiments have been carried out on five female Sprague-Dawley rats after calibration and testing with suitable phantoms containing known amounts of water and oil. We found that, in the interscapular BAT, the fat is about 50% at the surface (mainly unilocular) region, but its percentage drops to 20;-30% in the deepest (mainly multilocular) portion. The perirenal deposits of white adipose tissue (WAT) contained significantly higher amount of fat with large areas ranging from 70 to 90%. Later the rats were killed and the same procedure was repeated with dead animals. Experiments performed in dead rats show a modification of the hydro-lipidic ratio more evident in the multilocular portions of the deposit. The present work demonstrates that MRI-based methods allow a non-invasive, in vivo quantitative mapping of the lipid content which can be applied to investigation of brown adipose tissue deposits in small experiment animals.

Adipose Tissue, Brown↗
PubMed1998

Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation.

Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34(+) progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34(+) selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/microL (0.5 x 10(9)/L) and a nontransfused platelet count greater than 20,000/microL (20 x 10(9)/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We conclude that intense immunosuppressive conditioning and autologous T-cell-depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabilization or improvement.

Activities of Daily Living↗
PubMed1998

Significant changes in the tau A0 and A3 alleles in progressive supranuclear palsy and improved genotyping by silver detection.

BACKGROUND: Progressive supranuclear palsy (PSP) is characterized by intraneuronal inclusions of neurofibrillary tangles formed by aggregated tau protein. A significant association between the tau gene A0/A0 genotype and PSP recently has been reported. OBJECTIVES: To determine if a significant association between the tau gene A0/A0 genotype and PSP could be found in an independent population with a genetic background different from that in which the initial association was reported, and to standardize a nonradioactive method for tau gene genotyping. SETTING: Hospital and university research laboratories. SUBJECTS AND METHODS: To facilitate genotyping of the tau gene, we standardized the conditions for silver-based detection of the tau gene dinucleotide polymorphism. Thirty patients from Spain clinically diagnosed as having probable PSP were included in the study and compared with different control groups. RESULTS: A highly significant overrepresentation of the A0/A0 genotype (P<.001) and a decrease in the frequency of the A0/A3 genotype were found in the Spanish patients with PSP compared with the control group. A method based on silver detection was standardized for the genotyping of the tau gene. CONCLUSIONS: The detection of a significant association between the tau gene A0/A0 genotype and PSP in 2 independent populations rules out genetic stratification as an explanation for the association and indicates that the presence of the tau A0/A0 genotype is a risk factor for developing PSP independent of genetic background. Alternatively, the results could be interpreted as a protective effect of the A3 allele.

Aged↗
PubMed1998

Evolution strategy optimization for selective pulses in NMR

We present a first set of improved selective pulses, obtained with a numerical technique similar to the one proposed by Geen and Freeman. The novelty is essentially a robust and efficient "evolution strategy" which consistently leads, in a matter of minutes, to "solutions" better than those published so far. The other two ingredients are a "cost function," which includes contributions from peak and average radiofrequency power, and some understanding of the peculiar requirements of each type of pulse. For example, good solutions for self-refocusing pulses and "negative phase excitation pulses" (which yield a maximum signal well after the end of the pulse) are found, as may have been predicted, among amplitude modulated pulses with 270 degrees tip angles. Emphasis is given to the search for solutions with low RF power for selective excitation, saturation, and inversion pulses. Experimental verification of accuracy and power requirements of the pulses has been performed with a 4.7 T Sisco imager. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Ab Initio Determination of the Torsion-Wagging and Wagging-Bending Infrared Band Structure Spectrum of Methylamine.

The infrared band structure for the methyl torsion and amine hydrogen symmetric wagging in methylamine is calculated by ab initio procedures. The influence of the amine hydrogen symmetric bending on the wagging spectrum is considered explicitly. For this purpose, the potential energy surfaces and kinetic parameters were determined at the RHF/MP2 level with the 6-311G++(3df, 3dp) basis set. The numerical results were fitted to symmetry adapted functional forms. The Schrödinger equations for the nuclear motions were solved by expanding the solutions into products of trigonometric functions. The band frequencies and intensities were calculated from the energy levels, the vibrational functions, and the electric dipole moment variations. The calculated spectra were compared with the available experimental data. It was found that the torsional splittings and frequencies are relatively well reproduced, whereas the wagging and bending frequencies are slightly too high. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Progenitor cell subsets and engraftment kinetics in children undergoing autologous peripheral blood stem cell transplantation.

The main objective of the present study was to determine the role of CD34+ cell subsets in the haemopoietic recovery of children undergoing peripheral blood stem cell transplantation. For this purpose, 38 leukaphereses from 33 children with malignancies mobilized with G-CSF were analysed. Using dual-colour flow cytometry, different subpopulations of CD34+ cells were quantified and the number of each reinfused subsets correlated with haemopoietic resurgence. Multivariate analysis showed that the number of CD34+CD38- cells and CD34+CD38+ cells correlated better with time to neutrophil and platelet recovery, respectively, than the total number of CD34+ cells. Threshold values for rapid haemopoietic recovery, determined by the receiver operating characteristic analysis, were found to be 0.5 X 10(6) CD34+CD38- cells for neutrophil engraftment, and 2.0x10(6) CD34+CD38+ cells for platelet recovery. It is suggested that the analysis of CD34+ cell subsets could increase understanding of the repopulation capacity of a given leukapheresis product in peripheral blood stem cell transplantation procedures in children. In particular, this procedure could be extremely useful when low numbers of CD34+ cells are collected.

Adolescent↗
PubMed1998

Analysis of engraftment kinetics in pediatric patients undergoing autologous PBPC transplantation.

We sought to analyze factors that affect the engraftment kinetics following autotransplantation with PBPC mobilized by filgrastim (G-CSF). Forty-six consecutive pediatric patients with hematologic malignancies (n = 23) or solid tumors (n = 23) underwent autologous PBPC transplantation after myeloablative therapy. PBPC were mobilized using G-CSF alone. All patients received G-CSF after PBPC infusion. Factors potentially influencing the neutrophil and platelet engraftment were examined using univariate and multivariate analysis. All patients experienced rapid hematopoietic recovery, with a median of 9 days (range 7-15) to achieve a neutrophil count of 0.5 x 10(9)/L and a median of 15 days (range 9-37) to achieve a platelet count of 20 x 10(9)/L. The most important predictive factor of both platelet (p = 0.002) and neutrophil (p = 0.0001) recovery was the number of CD34+ cells infused. Patients receiving > or =5 x 10(6)/kg CD34+ cells had a more rapid hematopoietic recovery (p < 0.001) than those receiving a lower cell dose. The CD34+ cell dose is the most important predictive factor for engraftment kinetics after PBPC transplantation. Although a minimal CD34+ cell dose could not be defined, a dose > or =5 x 10(6)/kg CD34+ cells may be optimal to ensure rapid neutrophil and platelet recovery.

Adolescent↗
PubMed1998

Peripheral blood progenitor cell collection by large-volume leukapheresis in low-weight children.

Large-volume leukapheresis (LVL), defined as the processing of at least three blood volumes in a single session for peripheral blood progenitor cell (PBPC) collection, was performed in 32 small children weighing < or = 25 kg, aged 10 months to 8 years, with a variety of malignancies. Harvesting of PBPC was started after 4 days of cytokine (G-CSF, 12 micrograms/kg s.c.) alone. Procedures were performed using a continuous flow blood cell separator (COBE Spectra). The automated program of lymphocytapheresis was modified to achieve a collection rate of 0.9 ml/min. The extracorporeal line was primed with a unit of a packed red blood cells before the procedure. Acid citrate dextrose (ACD) was used as anticoagulant with an ACD inlet ratio of 1:14 and an ACD infusion rate of 1.1 ml/min/L of total blood volume. The inlet flow ranged between 6 and 35 ml/min (median 20 ml/min). A total of 37 apheresis procedures were performed (median 1, range 1-3). In 84% of patients, a single apheresis yields the minimum number of PBPC cells required for transplantation. No consistent side effects were observed, and LVL was well tolerated by children. A median of 7.7 x 10(8) kg MNC, 5.4 x 10(6)/kg CD34+, and 6.2 x 10(4)/kg CFU-GM per apheresis were harvested. Patients with neuroblastoma had a significantly lower yield than other patients. To date, 27 patients have been transplanted after myeloablative treatment, and rapid and sustained engraftment was achieved in all cases. The number of CD34+ cells infused was highly correlated with engraftment kinetics. LVL can be safely and easily performed in small children, allowing adequate PBPC collection for transplantation with rapid hematologic recovery.

Blood Specimen Collection↗
PubMed1998

Peripheral blood progenitor cells for autologous transplant in children.

Autologous peripheral blood progenitor cell transplantation has become an accepted procedure to support high dose chemotherapy in adults and children with cancer. The use of hematopoietic growth factors alone for mobilization of PBSC avoids the potential side effects of myelotoxic regimens and is as effective in reconstituting hematopoiesis as other mobilization methods. Many problems associated with apheresis procedures arise when PBPCs are harvested in small children. Large-volume-leukapheresis using a continuous flow blood cell separator allows us the collection of peripheral blood stem cells in children, even in the small ones. The speed of hematological recovery highly correlates with the number of CD34+ infused cells. We consider that a CD34+ cell dose of 5.0 x 10(6)/kg may be sufficient to ensure a rapid neutrophil and platelet recovery in pediatric patients mobilized by G-CSF.

Antigens, CD34↗