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Biomedical subjects

M J García

Publications and source records attributed to M J García.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Clinical factors that affect the detection of BCR-ABL transcripts after allogenic bone marrow transplantation for chronic myeloid leukemia].

BACKGROUND: To evaluate the relationship between clinical parameters and the ability to detect BCR-ABL-positive cells in a series of 27 long survivor patients after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML). PATIENTS AND METHODS: A total of 78 samples obtained between 1 and 160 months after BMT were analyzed for the presence of the BCR-ABL transcript detected by the reverse-transcription polymerase chain reaction (PCR) using nested primers. Median follow up was 83 months. RESULTS: 16 patients were persistently PCR-positive and 7 patients persistently PCR-negative. The original transcript became negative in four patients. Only two of the positive cases developed hematologic relapse during the period of study. High white blood cell counts before BMT (17.88 vs 10.12 x 10(9)/l; p = 0.008) and immunosuppressive therapy for chronic graft-versus-host disease (p < 0.05) were associated with an increased ability to detect residual BCR-ABL positive cells. CONCLUSIONS: Our data show that most patient are persistently BCR-ABL positive after BMT for CML. If these findings represents a dynamic balance between the tumour burden prior BMT and the immunological capability of the graft must be confirmed in further studies.

Adolescent↗
PubMed1998

Description of the characteristics of cases with noncontiguous neural tube defects identified in a series of consecutive births.

Van Allen et al. [(1973) Am. J. Med. Genet. 47:723-743] provided evidence for multisite closure of the neural tube in humans. Reynolds et al. [(1995) Proceedings of the Greewood Genetic Center 14:70-71] and Seller [(1995) J. Med. Genet. 32:205-207] described 13 and seven cases of noncontiguous neural tube defects (NTDs) respectively and concluded that the presence of noncontiguous NTDs cannot be explained on the basis of the model of a single initiation site with bidirectional closure. Here we present a series of 14 consecutive infants with noncontiguous NTDs, describing their characteristics. These show that noncontiguous NTDs are clinically heterogeneous, may have differences in sex ratio, and could have causal heterogeneity. The different combinations of closure failure defects have shown proportions in our population that are different from those in the populations studied by Reynolds et al. and Seller.

Birth Weight↗
PubMed1998

An unusual late-onset case of propionic acidaemia: biochemical investigations, neuroradiological findings and mutation analysis.

UNLABELLED: We report a 5-year-old boy with propionic acidaemia who developed a rapidly fatal necrosis of the basal ganglia after an episode of clinical deterioration. Neither metabolic acidosis nor hyperammonaemia were present. Organic acid analysis in both urine and CSF showed increased levels of methylcitric and 3-hydroxypropionic acids. Propionic acidaemia was confirmed by demonstrating a propionyl-CoA carboxylase deficiency (11% of control value) in skin fibroblasts. DNA analysis revealed that the patient was a compound heterozygote for two mutations in the PCCB gene. CONCLUSION: Propionic acidaemia can present as a sudden and fatal neurological disease and not only as an organic aciduria with severe biochemical dis-turbances and progressive neurological deterioration.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Hypermethylation of p15/ink4b/MTS2 gene is differentially implicated among non-Hodgkin's lymphomas.

P15 (MTS2) gene is a candidate tumor suppressor gene localized adjacent to the p16 gene at 9p21. Deletions at the 9p21 region frequently affect both p16 and p15 genes, however, mutations in the coding sequence of the p15 gene have not been found in the majority of tumors analyzed, including non-Hodgkin's lymphomas. Abnormal methylation of the promoter region of p15 has been recently described as an alternative mechanism of inactivation of this gene. We analyzed 72 non-Hodgkin's lymphomas (NHL) for methylation at p15 exon 1 by PCR and Southern blot techniques using methylation-sensitive restriction enzymes. Abnormal methylation was found in eight cases (11%), most of them (three MALT, one anaplastic T cell lymphoma, one Burkitt and one follicular lymphoma) showing hypermethylation in the p16 gene also. In contrast, two pleomorphic T cell NHL showed a selective methylation at p15 gene, while the p16 gene remained unmethylated. The results show that methylation at the p15 gene is frequently associated with p16 methylation in NHL, and suggest that selective methylation of p15, although uncommon, could be a specific alteration implicated in T cell NHL.

Carrier Proteins↗
PubMed1998

Importance of mixed chimerism to predict relapse in persistently BCR/ABL positive long survivors after allogeneic bone marrow transplantation for chronic myeloid leukemia.

Determination of hematological chimerism could be helpful in understanding the biology of leukemic relapse after allogeneic bone marrow transplant (BMT) for chronic myeloid leukemia (CML), because the detection of malignant residual cells carrying the bcr/abl message by qualitative RT-PCR is of limited value in predicting disease progression for individual patients. We have studied the chimerism pattern and the bcr/abl status by Southern-blot in 15 CML patients (M/F:6/9) transplanted with unmanipulated BM from HLA identical sibling donors, persistently bcr/abl positive by RT-PCR. The median age of the series was 31 years (18-49) and disease status at BMT was: chronic phase: 11, accelerated phase: 3 and blast crisis: 1 patient. Of the 15 patients, 9 are alive and in complete remission (CR), 4 have died in CR and 2 are alive but suffered relapse at + 19 and +26 months post-BMT. The median follow-up is 81 months (13,7-168). Rearrangement of the BCR gene was performed by Southern-blot using P32-labeled transprobe-1. PCR analysis of chimerism was assessed using primers for the following VNTR loci: D1S80, D1S111, 33.1, APO-B, YNZ-22, lambdag3 and DXS52. Seventy-nine samples were analyzed (median per patient 5 (range 2-9)). Thirteen patients showed complete chimerism and lacked BCR rearrangement over time by Southern-blot. The 2 patients who relapsed showed mixed chimera status from +9 and +5 months respectively until the end of the study. Persistent BCR rearrangement was observed in these 2 patients from +12 and +11 months respectively. Our data suggest that mixed chimerism may predict hematologic or cytogenetic relapse by several months in those patients who are persistently PCR-positive post-BMT.

Adult↗
PubMed1998

[Correlation of flow and static cytometry; their application to the study of anaplastic lymphomas].

PURPOSE: DNA study by cytometric methods is one of the prognosis factors considered in malignant tumours. Flow cytometry (FCM) was the most frequently used techniques in cell suspensions. Image cytometry (ICM) was also applied in cellular smears and it is possible to measure the results with an Image Analyzer, which supposes a substancial advantage over DNA studies. To confirm the results and correlation of the two techniques a controversial subtype of lymphoid tumour was selected: Anaplastic large cell lymphoma (ALCL). MATERIAL AND METHODS: Fifty four cases of ALCL (23 classical type and 31 ACL-Hodgkin related) were studied. Cytometry was performed in paraffin-embedded tissues previously dewaxed, rehydrated and minced. FCM was done in suspensions incubated with ribonuclease A and stained with propidium iodide in an EPICS-C flow cytometer. ICM study was performed in Feulgen-stained smears and measured by an Image Analyzer CAS-200. RESULTS: All cases were aneuploid. ALCL were 30.5% hypodiploid (HpD) and 69.5% hyperdiploid (HrD) by FCM; 43.5% HpD and 56.5% HrD by ICM. ALCL-HR were 58% HpD and 42% HrD by FCM; 68% HpD and 32% HrD by ICM. There was a lack of correlation of 22% between both methods but it was not statistically significant. CONCLUSIONS: We can conclude the obtained results by FCM and ICM are almost similar.

Aneuploidy↗
PubMed1997

Severe limb deficiencies, vertebral hypersegmentation, and mirror polydactyly: two additional cases that expand the phenotype to a more generalized effect on blastogenesis.

We report on 2 unrelated fetuses with a multiple congenital anomaly pattern of severe limb deficiencies, vertebral/rib alterations, and mirror polydactyly similar to that described previously by us [Urioste et al., Hum Genet 97:214-217, 1996]. In addition, the two cases we present here have a more extense alteration of blastogenesis, expanding the phenotype of the cases previously reported. We have suggested [Urioste et al., Hum Genet 97:214-217, 1996] that this condition may be caused by a mutation in a developmental control gene that affects body-plan organization. The minimal estimate of the prevalence of this new entity in our population (the Spanish Collaborative Study of Congenital Malformations, ECEMC) is 3.0/ 1,000,000 live births.

Abnormalities, Multiple↗
PubMed1997

Population pharmacokinetics of caffeine in premature neonates.

OBJECTIVE: To determine population pharmacokinetic parameters of caffeine in premature neonates. METHODS: This population analysis was done using 145 serum concentration measurements gathered from 75 hospitalized patients during their routine clinical care. The data were analysed by use of NONMEM (mixed effects modeling) according to a one-compartment open model with either zero or first-order absorption and first-order elimination. The effect of a variety of developmental, demographic and clinical factors (gender, birth weight, current weight, gestational age, postnatal age, postconceptional age and concurrent treatment with phenobarbital and parenteral nutrition) on clearance and volume of distribution was investigated. Forward selection and backward elimination regression identified significant covariates. RESULTS: The final pharmacostatistical model with influential covariates were as follows: clearance (m1.h-1) = 5.81-current weight (kg) + 1.22.postnatal age (weeks), multiplied by 0.757 if gestational age < or = 28 weeks and 0.836 if the current primary source of patients' nutrition is parenteral nutrition, and volume of distribution (ml) = 911.current weight (kg). The inter-individual variability in clearance and the residual variability, expressed as coefficients of variation, were 14.8%, and 18.44%, respectively. Due to the lack of information on the data set we were unable to characterize the interindividual variability for volume of distribution. CONCLUSION: In this study, which involved on average only two serum concentrations of caffeine per patient, the use of NONMEM gave us significant and consistent information about the pharmacokinetic profile of caffeine when compared with available bibliographic information. Additionally, parenteral nutrition and low gestational age (< or = 28 weeks) may even come to be considered as risk factors, and their presence may serve as an indicator of the need for periodic monitoring of caffeine concentrations in premature infants.

Caffeine↗
PubMed1997

katGI and katGII encode two different catalases-peroxidases in Mycobacterium fortuitum.

It has been suggested that catalase-peroxidase plays an important role in several aspects of mycobacterial metabolism and is a virulence factor in the main pathogenic mycobacteria. In this investigation, we studied genes encoding for this protein in the fast-growing opportunistic pathogen Mycobacterium fortuitum. Nucleotide sequences of two different catalase-peroxidase genes (katGI and katGII) of M. fortuitum are described. They show only 64% homology at the nucleotide level and 55% identity at the amino acid level, and they are more similar to catalases-peroxidases from different bacteria, including mycobacteria, than to each other. Both proteins were found to be expressed in actively growing M. fortuitum, and both could also be expressed when transformed into Escherichia coli and M. aurum. We detected the presence of a copy of IS6100 in the neighboring region of a katG gene in the M. fortuitum strain in which this element was identified (strain FC1). The influence of each katG gene on isoniazid (isonicotinic acid hydrazide; INH) susceptibility of mycobacteria was checked by using the INH-sensitive M. aurum as the host. Resistance to INH was induced when katGI was transformed into INH-sensitive M. aurum, suggesting that this enzyme contributes to the natural resistance of M. fortuitum to the drug. This is the first report showing two different genes encoding same enzyme activity which are actively expressed within the same mycobacterial strain.

Amino Acid Sequence↗
PubMed1996

Bayesian forecasting in paediatric populations.

Bayesian forecasting offers several important advantages for dosage individualisation in children, although, unlike for adults, its use in this population is much lower. Indeed, currently Bayesian methods are underused in this patient population. The paucity of paediatric population pharmacokinetic parameters, and the unavailability of specific clinical pharmacokinetic software for the whole paediatric population, are the main limitations to the application of Bayesian methods in these patients. When these problems have been overcome, this approach will allow clinicians to achieve therapeutic concentrations more readily, faster and more precisely, thus making the methodology highly attractive in the paediatric setting.

Adolescent↗
PubMed1996

Selenium and glutathione peroxidase reference values in whole blood and plasma of a reference population living in Valencia, Spain.

In order to assess the reference values for selenium nutritional status, adequate indicators (selenium concentration and glutathione peroxidase activity) were determined in whole blood and blood derivates of a healthy population (n = 287) from the province of Valencia, Spain. The reference population was selected by applying preestablished criteria. Selenium in whole blood and plasma was measured by graphite furnace atomic absorption spectrometry (GFAAS), with a deuterium correction, after addition of Pd/Mg(NO3)2 as the matrix modifier and appropriate dilution. Accuracy was checked by means of a reference material (Seronorm Trace Metals serum and whole blood). The population's reference intervals for selenium content at a 95% confidence level were: 53.03-108.96 and 66.71-119.4 mg/L for plasma and whole blood selenium concentration respectively. GPX activity was measured using a modification of the Paglia and Valentine method, and the reference intervals obtained ranged from 196 to 477 U/L in plasma, from 49 to 93 U/gHb in erythrocytes and from 52 to 96 U/gHb in whole blood. The only statistically significant differences detected between men and women are for to the GPX activity in whole blood. The results obtained are in the range of values found by others authors in healthy populations residing in different European countries.

Adolescent↗
PubMed1994

Predictive performance of two phenytoin pharmacokinetic dosing programs from nonsteady state data.

The present work evaluated the performance of two computer programs: Drugcalc, which utilizes the bayesian (method 1) approach and PKS, which can utilize both the non-bayesian (method 2) and bayesian (method 3) approaches. Both programs permit the introduction of serum level data obtained in both situations: steady-state and nonsteady-state. The prediction of phenytoin concentrations (n = 771) were made from steady-state (n = 378) and nonsteady-state (n = 175), and combined steady-state and nonsteady-state (n = 218) concentrations. The observed serum concentrations (at least two nonsteady-state and two steady-state per patient) were collected under routine clinical conditions in 15 patients receiving this drug. The main contribution to prediction errors is attributed to the difference between doses corresponding to the predicted and feedback serum concentrations, dD, in such a way that when the errors obtained for dD > or = 100 mg/day are excluded, the predictive performance increases significantly for all methods. In this sense, increases in precision were 87, 64, and 66% for methods 1, 2, and 3, respectively. Moreover, when dD < 100 mg/day, nonsteady-state feedback concentrations (< or = 3) only afforded clinically acceptable predictions (ME +/- SD < 3 mg/L) when they were combined with at least one steady-state datum value, and the bayesian approach was used. Despite this, for all the methods analyzed, nonsteady-state data are seen to be useful for detecting situations of potential toxicity in a significant proportion of cases (71.4-84.6%) and, when method 3 is used, may offer useful information for the adjustment of dosage schedules.

Adolescent↗