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1.
Rev Neurol ; 66(12): 397-408, 2018 06 16.
Article in Spanish | MEDLINE | ID: mdl-29897607

ABSTRACT

AIM: To analyze the frequency of use of the Montreal Cognitive Assessment (MoCA) as a cognitive screening instrument, cross-cultural adaptation, the existence of normative data and clinical validation studies in Latin America Hispanic countries. SUBJECTS AND METHODS: The Medline, PsycINFO, Web of Science, Scopus and Scielo databases were consulted between April and June 2017 according to the PRISMA methodology. We included all studies referencing the MoCA as an instrument to evaluate cognitive deterioration conducted in Latin America and that included normative and psychometric data, as well as its clinical validation. RESULTS: Of the 80 studies identified, 19 met the inclusion criteria. Most of the studies mentioned the use of the Spanish version of the MoCA and reported a statistically significant effect of gender, age and, most of all, education on the performance of this test. Only five studies presented with a detailed analysis of the psychometric characteristics of the test, and in most articles cut-off scores for the diagnosis of cognitive impairment were the same as the original study. CONCLUSIONS: The small number of articles identified may reflect a late start of the use of MoCA in Latin America. A tendency towards the use of this test without making a cross-cultural adaptation and the use of international norms was observed in this region. The present systematic review demonstrates the need for future research tackling the development of a linguistically adapted version of the MoCA to Latin America and the study of its psychometric properties, with the aim of improving cognitive assessment.


TITLE: Uso del test de evaluacion cognitiva de Montreal (MoCA) en America Latina: revision sistematica.Objetivo. Analizar la frecuencia del uso del test de evaluacion cognitiva de Montreal (MoCA) como instrumento de cribado cognitivo, su adaptacion transcultural, la existencia de baremos y estudios de validacion clinica en paises de habla hispana en America Latina. Sujetos y metodos. Se ha realizado una revision sistematica de todos los estudios desarrollados en America Latina, con referencia al MoCA, que incluyan datos normativos, datos psicometricos y estudios de baremacion o de validacion clinica. Fueron consultadas sistematicamente, entre abril y junio de 2017, las bases de datos Medline, PsycINFO, Web of Science, Scopus y Scielo, conforme a la metodologia PRISMA. Resultados. De los 80 estudios encontrados, 19 cumplieron los criterios de inclusion. La mayoria de los estudios menciona el uso de la version española y comunica un efecto significativo del sexo, la edad y la escolaridad. El punto de corte adoptado por la mayoria de los autores para el diagnostico de deterioro cognitivo es el mismo del estudio original. Conclusiones. El reducido numero de articulos identificados refleja posiblemente un inicio tardio de la utilizacion del MoCA en America Latina. Esto pone de manifiesto una tendencia en la region a utilizar la prueba sin hacer una adaptacion transcultural de la version original y sin recurrir a normas internacionales para el diagnostico. La presente revision sistematica demuestra la necesidad de trabajos futuros de investigacion que puedan ofrecer una version linguisticamente adaptada del MoCA para America Latina y un estudio de sus propiedades psicometricas, con miras a una evaluacion cognitiva de mayor calidad.


Subject(s)
Cognitive Dysfunction/diagnosis , Dementia/diagnosis , Mental Status and Dementia Tests , Aged , Aged, 80 and over , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/psychology , Culturally Competent Care , Dementia/epidemiology , Dementia/psychology , Early Diagnosis , Educational Status , Female , Humans , Latin America/epidemiology , Male , Middle Aged , Observer Variation , Procedures and Techniques Utilization , Psychometrics , Reproducibility of Results , Translations
2.
NeuroRehabilitation ; 41(3): 673-686, 2017.
Article in English | MEDLINE | ID: mdl-28946591

ABSTRACT

OBJECTIVE: To generate normative data for the phonological and semantic verbal fluency tests (VFT) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the VFT as part of a larger neuropsychological battery. Scores for letters F, A, S, and animals and fruit categories were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on all scores, such that scores increased linearly as a function of age. Age2 had a significant effect in Chile (animals), Cuba (A letter, fruits), Ecuador (animals, fruits), Honduras (F letter), Mexico (animals, fruits), Peru (fruits), and Spain (S letters, animals, fruits). Models showed an effect for MLPE in Chile (A letters, animals, fruits), Ecuador (S letter, animals, fruits), Guatelama (F, S letter, animals), Honduras (animals), Mexico (F, A, S letters, animals, fruits), Puerto Rico (A, letters, animals), and Spain (all scores). Sex scores were found significant in Chile (animals), Ecuador (A letter, fruits), Mexico (F letter, fruits), Paraguay (F, A, S letters, fruits), Puerto Rico (F letter, animals, fruits), and Spain (F letter, fruits). CONCLUSIONS: This is the largest multi-national Spanish speaking-pediatric normative study in the world, and as such it will allow neuropsychologists from these countries to have a more accurate way to interpret the phonological and semantic VFT in pediatric populations.


Subject(s)
Language Tests/standards , Child , Humans , Language , Latin America , Spain
3.
NeuroRehabilitation ; 41(3): 617-626, 2017.
Article in English | MEDLINE | ID: mdl-28946592

ABSTRACT

OBJECTIVE: To generate normative data for the Modified Wisconsin Card Sorting Test (M-WCST) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the M-WCST as part of a larger neuropsychological battery. Number of categories, perseverative errors, and total error scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models indicated main effects for age on all scores, such that the number of categories correct increased and total number of perseverative errors and total number of errors decrease linearly as a function of age. Age2 had a significant effect in Chile, Cuba, Ecuador, and Spain for numbers of categories; a significant effect for number of perseverative errors in Chile, Cuba, Mexico, and Spain; and a significant effect for number of total errors in Chile, Cuba, Peru, and Spain. Models showed an effect for MLPE in Cuba (total errors), Ecuador (categories and total errors), Mexico (all scores), Paraguay (perseverative errors and total error), and Spain (categories and total errors). Sex affected number of total errors for Ecuador. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate way to interpret the M-WCST with pediatric populations.


Subject(s)
Neuropsychological Tests/standards , Child , Humans , Language , Latin America , Linear Models
4.
NeuroRehabilitation ; 41(3): 649-659, 2017.
Article in English | MEDLINE | ID: mdl-28946594

ABSTRACT

OBJECTIVE: To generate normative data for the Shortened Version of the Token Test in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the Shortened Version of the Token Test as part of a larger neuropsychological battery. Shortened Version of the Token Test total scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age in all countries, such that score increased linearly as a function of age. In addition, age2 had a significant effect in all countries, except Guatemala and Puerto Rico. Models showed that children whose parent(s) had a MLPE >12 years obtained higher score compared to children whose parents had a MLPE ≤12 years in Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, Puerto Rico, and Spain. The child's sex did not have an effect in the Shortened Version of the Token Test total score for any of the countries. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate interpretation of the Shortened Version of the Token Test when used in pediatric populations.


Subject(s)
Psychological Tests/standards , Child , Humans , Latin America , Linear Models , Spain
5.
NeuroRehabilitation ; 41(3): 605-616, 2017.
Article in English | MEDLINE | ID: mdl-28946595

ABSTRACT

OBJECTIVE: To generate normative data for the Stroop Word-Color Interference test in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the Stroop Word-Color Interference test as part of a larger neuropsychological battery. The Stroop Word, Stroop Color, Stroop Word-Color, and Stroop Interference scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on all scores, except on Stroop Interference for Guatemala, such that scores increased linearly as a function of age. Age2 affected Stroop Word scores for all countries, Stroop Color scores for Ecuador, Mexico, Peru, and Spain; Stroop Word-Color scores for Ecuador, Mexico, and Paraguay; and Stroop Interference scores for Cuba, Guatemala, and Spain. MLPE affected Stroop Word scores for Chile, Mexico, and Puerto Rico; Stroop Color scores for Mexico, Puerto Rico, and Spain; Stroop Word-Color scores for Ecuador, Guatemala, Mexico, Puerto Rico and Spain; and Stroop-Interference scores for Ecuador, Mexico, and Spain. Sex affected Stroop Word scores for Spain, Stroop Color scores for Mexico, and Stroop Interference for Honduras. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the Stroop Word-Color Interference test in pediatric populations.


Subject(s)
Stroop Test/standards , Child , Female , Humans , Latin America , Linear Models , Male
6.
Neuroscience ; 154(3): 1143-53, 2008 Jun 26.
Article in English | MEDLINE | ID: mdl-18479826

ABSTRACT

While the onset and extent of epilepsy increases in the aged population, the reasons for this increased incidence remain unexplored. The present study used two inbred strains of mice (C57BL/6J and FVB/NJ) to address the genetic control of age-dependent neurodegeneration by building upon previous experiments that have identified phenotypic differences in susceptibility to hippocampal seizure-induced cell death. We determined if seizure induction and seizure-induced cell death are affected differentially in young adult, mature, and aged male C57BL/6J and FVB/NJ mice administered the excitotoxin, kainic acid. Dose response testing was performed in three to four groups of male mice from each strain. Following kainate injections, mice were scored for seizure activity and brains from mice in each age group were processed for light microscopic histopathologic evaluation 7 days following kainate administration to evaluate the severity of seizure-induced brain damage. Irrespective of the dose of kainate administered or the age group examined, resistant strains of mice (C57BL/6J) continued to be resistant to seizure-induced cell death. In contrast, aged animals of the FVB/NJ strain were more vulnerable to the induction of behavioral seizures and associated neuropathology after systemic injection of kainic acid than young or middle-aged mice. Results from these studies suggest that the age-related increased susceptibility to the neurotoxic effects of seizure induction and seizure-induced injury is regulated in a strain-dependent manner, similar to previous observations in young adult mice.


Subject(s)
Aging/pathology , Excitatory Amino Acid Agonists , Kainic Acid , Neurons/pathology , Seizures/chemically induced , Seizures/pathology , Animals , Cell Count , Cell Death/drug effects , Cell Death/physiology , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred C57BL , Neurons/drug effects , Seizures/genetics , Species Specificity
7.
Genes Brain Behav ; 7(5): 587-98, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18363852

ABSTRACT

Inbred strains of mice differ in their susceptibility to excitotoxin-induced cell death, but the genetic basis of individual variation in differential susceptibility is unknown. Previously, we identified a highly significant quantitative trait locus (QTL) on chromosome 18 that influenced susceptibility to kainic acid-induced cell death (Sicd1). Comparison of susceptibility to seizure-induced cell death between reciprocal congenic lines for Sicd1 and parental background mice indicates that genes influencing this trait were captured in both strains. Two positional gene candidates, Galr1 and Mbp, map to 55 cM, where the Sicd1 QTL had been previously mapped. Thus, this study was undertaken to determine if Galr1 and/or Mbp could be considered as candidate genes. Genomic sequence comparison of these two functional candidate genes from the C57BL/6J (resistant at Sicd1) and the FVB/NJ (susceptible at Sicd1) strains showed no single-nucleotide polymorphisms. However, expression studies confirmed that Galr1 shows significant differential expression in the congenic and parental inbred strains. Galr1 expression was downregulated in the hippocampus of C57BL/6J mice and FVB.B6-Sicd1 congenic mice when compared with FVB/NJ or B6.FVB-Sicd1 congenic mice. A survey of Galr1 expression among other inbred strains showed a significant effect such that 'susceptible' strains showed a reduction in Galr1 expression as compared with 'resistant' strains. In contrast, no differences in Mbp expression were observed. In summary, these results suggest that differential expression of Galr1 may contribute to the differences in susceptibility to seizure-induced cell death between cell death-resistant and cell death-susceptible strains.


Subject(s)
Cell Death/genetics , Epilepsy/genetics , Epilepsy/pathology , Genetic Predisposition to Disease/genetics , Receptor, Galanin, Type 1/genetics , Animals , Base Sequence , Epilepsy/chemically induced , Excitatory Amino Acid Agonists/toxicity , Genetic Variation , Genomics , Haplotypes , Hippocampus/pathology , Hippocampus/physiology , Kainic Acid/toxicity , Male , Mice , Mice, Congenic , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred DBA , Myelin Basic Protein , Nerve Tissue Proteins/genetics , Neurotoxins/toxicity , Phenotype , Polymorphism, Single Nucleotide , Species Specificity , Transcription Factors/genetics
8.
Plant Dis ; 91(11): 1513, 2007 Nov.
Article in English | MEDLINE | ID: mdl-30780767

ABSTRACT

Horse chestnut (Aesculus hippocastanum L.) is an important ornamental tree in many gardens in Castilla y León (northern Spain). During the summer and autumn of 2005 and 2006, disease signs resembling powdery mildew were observed in Condesa de Sagasta Boulevard and Quevedo Botanical Garden in León. Whitish fungal growth was visible macroscopically on the upper and lower leaf surfaces of both young and old leaves and petioles. The disease reduced tree attractiveness and could cause important aesthetic damage in the parks. Five symptomatic trees older than 30 years were observed in each park, and 10 leaves per tree were collected. Microscopic examinations of the leaf surfaces revealed ectophytic, hyaline hyphae with lobed appresoria, solitary or in pairs. Conidia were barrel to broadly subglobose and ranged from 23 to 37 µm long and 8 to 16 µm wide. They were produced singly on two- or three-celled conidiophores. Chasmothecia were produced in abundance, mostly on the lower leaf surface. They were globose, 120 to 160 µm in diameter, dark brown, and bore two types of appendages; long and flexuous with simple hook-like apices or short, simple, tapered, and rough walled. The long appendages measured 87 to 182 µm and the shorter ones measured 12 to 32 µm. Chasmothecia contained three to five asci, each developing six to eight hyaline, round, and single-celled ascospores when matured. Pathogenicity was confirmed on Aesculus sp. branches by healthy leaves being inoculated by touching them with powdery mildew-infected leaves. Noninoculated leaves served as controls. The appearance of colonies in the infected leaves was observed 15 days after the inoculation, but not in the controls. The pathogen was identified as Erysiphe flexuosa (Peck) U. Braun & S. Takamatsu, a North American powdery mildew. It has been recently introduced in Europe (1) and is now present in a number of countries (2). To our knowledge, this is the first report of E. flexuosa in this region of Spain. References: (1) N. Ale-Agha et al. Cryptogam. Mycol. 21:89, 2000. (2) K. Zimmermannová-Pastircáková et al. Schlechtendalia 8:39, 2002.

9.
Leuk Lymphoma ; 40(5-6): 599-611, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11426532

ABSTRACT

A permanent cell line, HSC-M1, was established from a child with advanced CD30 (Ki-1)+ anaplastic large-cell lymphoma (ALCL). Clinical features included irritability, fever, weight loss, tender lymphadenopathy, pneumonitis, neutrophilia, and bone marrow erythrophagocytosis. While HSC-M1 cells exhibited an immunophenotype characteristic of ALCL of T-cell lineage, the cell line also demonstrated features of monocyte-macrophage lineage. Cytogenetic and polymerase chain reaction (PCR) analysis of the HSC-M1 cell line and involved bone marrow demonstrated the characteristic non-random chromosomal translocation t(2:5)(p23:q35). Reverse transcriptase PCR for mRNA expression of cytokines and cytokine receptors showed that HSC-M1 cells expressed the message for multiple cytokines and their receptors. Measurement of cytokine levels in serum samples using enzyme-linked immunosorbent assays showed increased concentrations of several cytokines. The increased levels of some cytokines correlated with disease activity and clinical symptoms. Although spontaneous production by HSC-M1 cells of some of these cytokines was demonstrated, the production of others was only detectable after stimulation with exogenous CD30 ligand. With few exceptions, there was good correlation between serum cytokine levels and cytokines produced by HSC-M1 cells. These findings indicate that cytokine production is a feature of ALCL cells and that some of the clinical manifestations in ALCL may result from cytokines produced by either the malignant or accessory cells.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Tumor Cells, Cultured , Chromosomes, Human, Pair 2 , Chromosomes, Human, Pair 5 , Cytokines/metabolism , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/pathology , Translocation, Genetic
10.
Pediatr Dev Pathol ; 4(2): 129-37, 2001.
Article in English | MEDLINE | ID: mdl-11178628

ABSTRACT

Anaplastic large cell lymphoma (ALCL) was proposed as a clinicopathologic entity over 14 years ago, but has been somewhat controversial due to the variability of its defining features and variable occurrence in different age-groups. To evaluate this entity in a pediatric population, 36 cases of childhood large cell lymphoma were evaluated for abnormalities of the anaplastic lymphoma kinase (ALK) gene that has been associated with ALCL morphology and immunophenotype. ALK abnormalities were evaluated by assay for the t(2;5)(p23;q35) translocation by RT-PCR and/or expression of NPM-ALK fusion protein by immunohistochemistry. Results showed 17 patients to have evidence of ALK gene expression. All of these children (mean age, 9.3 years) had tumors that were of T-cell phenotype (with the exception of a single case of null phenotype) and that expressed CD30. In contrast, 19 children with no evidence of ALK expression were older (mean, 12.7 years), and the majority (12/19) had tumors of B-cell phenotype. CD30 was also diffusely expressed in 8 of these 19 tumors. The difference in mean age between the two groups was statistically significant (P = 0.015). In three cases tested for both ALK and the t(2;5), ALK protein was detected in the absence of the t(2;5) translocation but no cases showed the reverse pattern, consistent with ALK fusion to genes other than NPM or activation of the ALK gene by another mechanism. These findings provide further support that ALK-positive ALCL is a distinct pathologic entity among pediatric large cell lymphomas primarily characterized by expression of T-cell markers, CD30, and EMA, and by a younger mean age.


Subject(s)
Chromosomes, Human, Pair 2 , Chromosomes, Human, Pair 5 , Lymphoma, Large-Cell, Anaplastic , Protein-Tyrosine Kinases/genetics , Translocation, Genetic , Adolescent , Anaplastic Lymphoma Kinase , Antigens, Neoplasm/analysis , Artificial Gene Fusion , B-Lymphocytes/chemistry , B-Lymphocytes/pathology , Biomarkers, Tumor/analysis , Child , Child, Preschool , DNA, Neoplasm/analysis , Female , Humans , Immunoenzyme Techniques , Ki-1 Antigen/analysis , Lymphoma, Large-Cell, Anaplastic/enzymology , Lymphoma, Large-Cell, Anaplastic/genetics , Lymphoma, Large-Cell, Anaplastic/pathology , Male , Mucin-1/analysis , Nuclear Proteins/analysis , Nuclear Proteins/genetics , Protein-Tyrosine Kinases/analysis , Protein-Tyrosine Kinases/metabolism , Receptor Protein-Tyrosine Kinases , Reverse Transcriptase Polymerase Chain Reaction , T-Lymphocytes/chemistry , T-Lymphocytes/pathology
12.
Cancer Genet Cytogenet ; 105(1): 50-4, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9689930

ABSTRACT

Chromosomal analysis of tumor tissue from two children with alveolar rhabdomyosarcoma revealed t(1;5)(q32;q31) and t(1;22)(q21;q11.2) in all metaphases examined, respectively. Peripheral blood lymphocytes carried the same cytogenetic abnormality as that of the tumor cells in both patients. Parental lymphocytes were karyotypically normal in the patient with t(1;22), indicating a de novo constitutional translocation, but t(1;5) was paternally inherited in the other patient. The presence of constitutional translocations in these two children might have contributed to the development of alveolar rhabdomyosarcoma.


Subject(s)
Muscle Neoplasms/genetics , Rhabdomyosarcoma, Alveolar/genetics , Translocation, Genetic/genetics , Child , Child, Preschool , Chromosomes, Human, Pair 1/genetics , Chromosomes, Human, Pair 22/genetics , Chromosomes, Human, Pair 5/genetics , Fatal Outcome , Humans , Karyotyping , Leg , Male , Spinal Neoplasms/genetics
14.
Pediatr Pathol Lab Med ; 17(6): 875-83, 1997.
Article in English | MEDLINE | ID: mdl-9353827

ABSTRACT

Amplification of MYCN portends rapid tumor progression and poor prognosis in neuroblastoma. MYCN copy number has been described as homogeneous within a tumor and congruent in primary tumor and metastasis. We report a child with stage III favorable histology stroma-rich neuroblastoma (ganglioneuroblastoma) and a poor outcome with an apparent change in MYCN gene amplification by Southern blot. Initial biopsy revealed a ganglioneuroblastoma with predominance of differentiating cells designated as neuroblastoma, stroma-rich, intermixed (Shimada). Southern blot failed to demonstrate MYCN gene amplification. After front-line chemotherapy failed, a total resection was performed. In this specimen, Southern blot demonstrated MYCN amplification (15-20 copies) in the undifferentiated component and no amplification in the differentiated. Fluorescence in situ hybridization (FISH) analysis performed retrospectively on both tumor biopsies demonstrated MYCN amplification in the undifferentiated sections of both tumor specimens but not in the differentiated ones. This is the first well-documented case report of heterogeneous MYCN amplification in a child with neuroblastoma. Because key therapeutic decisions are based on the presence of MYCN amplification, physicians diagnosing and treating children with neuroblastoma need to be aware of the possibility that MYCN amplification may be heterogeneous within a tumor and may be missed using techniques based on pooled DNA such as Southern blotting. FISH may be a preferable method for determining MYCN amplification.


Subject(s)
Ganglioneuroblastoma/genetics , Gene Amplification , Genes, myc/genetics , Retroperitoneal Neoplasms/genetics , Blotting, Southern , Child, Preschool , DNA, Neoplasm/analysis , Female , Ganglioneuroblastoma/pathology , Heterozygote , Humans , In Situ Hybridization, Fluorescence , Microscopy, Fluorescence , Neoplasm Staging , Retroperitoneal Neoplasms/pathology
15.
Crit Care Med ; 24(9): 1498-500, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8797621

ABSTRACT

OBJECTIVE: To determine the effect of enteral tube feedings on the measurement of gastric intramucosal pH. DESIGN: Interventional study. SETTING: Two intensive care units of a university-affiliated teaching hospital. PATIENTS: Twenty hemodynamically stable patients undergoing mechanical ventilation, with a nasogastric tonometer in situ, in whom enteral feeding was initiated. INTERVENTIONS: The baseline fasting gastric intramucosal pH and gastric fluid pH were determined in the study population. The patients then received enteral feedings for 2 hrs, after which the gastric intramucosal pH and gastric fluid pH measurements were repeated. The tube feedings were then withheld for 2 hrs. The data set was repeated 1 and 2 hrs after the feedings had been stopped. Finally, tube feedings were retarded and the data set was repeated after 4 hrs. All patients received a histamine-2 (H2)-receptor antagonist-blocking agent during the study. To investigate the possibility that a direct reaction between gastric fluid and enteral feedings may generate CO2, 30-mL aliquots of gastric fluid from an independent sample of 14 patients (seven receiving cimetidine) were mixed with 60 mL of enteral feeding in an airtight container; the PCO2 of the gastric fluid before and after adding enteral feeding was measured tonometrically. MEASUREMENTS AND MAIN RESULTS: The mean +/- SD gastric intramucosal pH decreased from 7.40 +/- 0.08 to 7.33 +/- 0.12 (p < .005), and from 7.38 +/- 0.07 to 7.31 +/- 0.1 (p < .005) after the first and second feeding challenges, respectively. The gastric intramucosal pH returned to the baseline value after 1 hr of fasting. The mean in vitro PCO2 of the gastric fluid increased from 11.9 +/- 3.0 to 16.2 +/- 2.0 torr (1.6 +/- 0.4 to 2.1 +/- 0.27 kPa) (p = .003) after the addition of tube feedings in the samples from those patients who were not receiving H2 receptor antagonists, but did not change significantly in those samples from the patients who were receiving H2 receptor antagonists. CONCLUSIONS: Enteral feeding stimulates the secretion of hydrogen ions, which are then buffered by ionized bicarbonate secreted by the nonparietal gastric cells generating CO2. In addition, the enzymatic digestion of nutrients in the stomach may also generate CO2. The increased intraluminal CO2 following enteral feeding results in a spuriously low gastric intramucosal pH reading. Our data suggest that tube feedings should be temporarily discontinued for at least 1 hr when measuring the gastric intramucosal pH. These data should, however, be used with caution when extrapolating to hemodynamically unstable patients. Furthermore, the consequences of frequent interruptions of enteral feeding need to be weighed against the possible benefits derived from the use of this monitoring tool.


Subject(s)
Carbon Dioxide/metabolism , Enteral Nutrition , Gastric Acidity Determination , Gastric Mucosa/metabolism , APACHE , Aged , Critical Care , Female , Gastric Mucosa/chemistry , Gastric Mucosa/drug effects , Histamine H2 Antagonists/pharmacology , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Respiration, Artificial
16.
Am J Pathol ; 148(4): 1125-38, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8644855

ABSTRACT

The presence of t(11;22)(q24;q12) is often considered diagnostic of Ewing sarcoma and peripheral primitive neuroectodermal tumor. We report four cases, all of which possessed this translocation as detected by reverse transcriptase polymerase chain reaction and confirmed by sequencing with or without fluorescent in situ hybridization, but none of which were Ewing sarcoma or peripheral primitive neuroectodermal tumor by histological criteria. Two were polyphenotypic tumors and two were mixed embryonal and alveolar rhabdomyosarcomas. Only one case was positive for MIC2 by immunohistochemistry and only in a rare cell. Two cases (one polyphenotypic tumor and one rhabdomyosarcoma) had double minute chromosomes with > 100 copies of the MDM2 gene. The presence of the t(11;22)(q24;ql2) translocation should probably not be considered diagnostic of Ewing sarcoma and peripheral primitive neuroectodermal tumor in the absence of supporting histological evidence. The presence of this translocation in Ewing sarcoma and peripheral primitive neuroectodermal tumor has been taken as evidence that these two tumors are related. Extending this relationship to include some polyphenotypic tumors and some rhabdomyosarcomas may not be justified unless additional evidence is gathered. Pathologists and oncologists will need to decide whether treatment regimens for tumors are better based on phenotype rather than genotype when these two profiles are seemingly in conflict.


Subject(s)
DNA-Binding Proteins/genetics , Neuroectodermal Tumors, Primitive/pathology , Proto-Oncogene Proteins , Sarcoma, Ewing/genetics , Sarcoma, Ewing/pathology , Trans-Activators/genetics , Transcription, Genetic , Abdominal Neoplasms/pathology , Biomarkers, Tumor/analysis , Bone Neoplasms/pathology , Brain Neoplasms/pathology , Child, Preschool , Diagnosis, Differential , Female , Genetic Markers , Humans , Infant , Male , Neuroectodermal Tumors, Primitive/diagnosis , Neuroectodermal Tumors, Primitive/genetics , Polymerase Chain Reaction , Proto-Oncogene Protein c-fli-1 , Sarcoma, Ewing/diagnosis
17.
Pediatr Pathol Lab Med ; 16(1): 119-28, 1996.
Article in English | MEDLINE | ID: mdl-8963622

ABSTRACT

Peripheral primitive neuroectodermal tumors (PNETs) consistently demonstrate a reciprocal translocation, t(11;22)(q24;q12). This translocation has not been found in PNETs of the central nervous system including the cerebellar medulloblastoma. We report an unusual cerebellar PNET in a 4-year-old boy in which tumor cells were surrounded by pools of Alcian blue-positive material. Tumor cells were immunoreactive for neuron-specific enolase and synaptophysin. Electron microscopy revealed well-developed rough endoplasmic reticulum, cell processes with intermediate filaments, microtubules, and dense core granules, and extracellular material reminiscent of mucopolysaccharide. Reverse transcriptase polymerase chain reaction (PCR) revealed an 11;22 translocation-specific PCR product. Clinically the tumor was a cerebellar PNET with leptomeningeal dissemination and there was no evidence to suggest that it was metastatic. Histopathology, however, was indicative of an unusual PNET that also manifested t(11;22) and was associated with an aggressive clinical course.


Subject(s)
Cerebellar Neoplasms/genetics , Cerebellar Neoplasms/pathology , Chromosomes, Human, Pair 11 , Chromosomes, Human, Pair 22 , Neuroectodermal Tumors, Primitive/genetics , Neuroectodermal Tumors, Primitive/pathology , Translocation, Genetic , Cerebellar Neoplasms/diagnostic imaging , Child, Preschool , Humans , Male , Neuroectodermal Tumors, Primitive/diagnostic imaging , Polymerase Chain Reaction , Radiography
18.
Blood ; 85(10): 2829-38, 1995 May 15.
Article in English | MEDLINE | ID: mdl-7742544

ABSTRACT

A new cell line, SBH-1, with the morphologic, immunophenotypic, and karyotypic features consistent with those of Reed-Sternberg (RS) and Hodgkin (H) cells, has been established from the pleural effusion of a patient. The cytologic appearance of SBH-1 cells is characteristic of multinucleate RS and mononuclear H cells, all containing inclusion-like nucleoli. The SBH-1 cells express CD30, CD15, CD25, CD71, CD45, CD20, CD22, and bcl-2 protein and are negative for epithelial membrane antigen. Cytogenetic analysis showed multiple clonal abnormalities with breakpoints at 14q32, 6q21, and 11q23. The Ig heavy chain genes and both Ig light chain genes were rearranged in SBH-1 cells, whereas the bcl-2 gene was in germline configuration. Messages for the cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha, and transforming growth factor-beta and the cytokine receptors IL-2R, IL-4R, IL-6R, and IL-7R were detected by reverse transcription-polymerase chain reaction analysis. Xenotransplantation of SBH-1 cells into severe combined immunodeficient (SCID) mice led to local and disseminated tumor growth. The cytologic, histologic, and immunohistochemical features of SBH-1 cells in SCID mouse tumors were typical of RS and H cells. The SBH-1 cell line will be useful in the study of RS and H cell biology, inasmuch as it represents a cell line obtained from a previously untreated patient.


Subject(s)
Cell Line , Hodgkin Disease/pathology , Reed-Sternberg Cells , Aged , Animals , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 18 , Cytokines/genetics , Female , Gene Expression , Genes, Immunoglobulin , Humans , Immunophenotyping , Karyotyping , Mice , Mice, SCID , Neoplasm Transplantation , RNA, Messenger/genetics , RNA, Neoplasm/genetics , Receptors, Cytokine/genetics , Translocation, Genetic , Transplantation, Heterologous
19.
Am J Hematol ; 47(1): 27-32, 1994 Sep.
Article in English | MEDLINE | ID: mdl-8042612

ABSTRACT

To determine whether recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) can offset the myelosuppressive effects of intensive chemotherapy, we carried out a double-blind placebo-controlled trial in which 40 patients with acute lymphoblastic leukemia (ALL) were randomized into two groups of 20 each. One group received rhGM-CSF (5.5 micrograms/kg SC) coadministered with chemotherapy and the other, placebo coadministered with chemotherapy from day 5 to day 11 and from day 19 to day 25 of the 28-day intensification phase of our institutional high-risk protocol for childhood ALL. The results indicate that, at the dose and schedule used, rhGM-CSF did not prevent neutropenia or shorten the number of days required to complete this phase of therapy. In addition, the treated and placebo groups showed no significant difference in absolute neutrophil counts, number of days with neutropenia, number of days with fever, number of days spent in hospital, or number of days on antibiotics during the 28-day study period. There was also no difference between the two groups in the number, type, or severity of infectious episodes. Two of 20 patients in the treatment group have relapsed, whereas none of the patients in the placebo group has yet relapsed (follow-up: 3-37 months), but these events were not statistically significant. We conclude that treatment with rhGM-CSF at the dose and schedule employed is not clinically beneficial.


Subject(s)
Bone Marrow/drug effects , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Child , Child, Preschool , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Male , Neutropenia/chemically induced , Recombinant Proteins/pharmacology
20.
Med Pediatr Oncol ; 23(2): 136-9, 1994.
Article in English | MEDLINE | ID: mdl-8202037

ABSTRACT

Acute tumour lysis syndrome (ATLS) is a common complication of the treatment of haematopoietic malignancies. It is also well recognized in many nonhaematopoeitic malignancies of adults. There are very few reports of the syndrome occurring during therapy for the nonhaematopoeitic malignancies of childhood, and none has previously been reported in the treatment of neuroblastoma. We report the cases of four patients presenting to The Hospital for Sick Children (HSC) between 1985 and 1992 who developed ATLS during treatment for stage IVS neuroblastoma. ATLS is a significant risk in patients undergoing therapy for stage IVS neuroblastoma, particularly where this has been delayed.


Subject(s)
Neuroblastoma/complications , Tumor Lysis Syndrome/etiology , Acute Disease , Adrenal Cortex Neoplasms/complications , Adrenal Cortex Neoplasms/secondary , Antineoplastic Agents/adverse effects , Female , Humans , Infant , Infant, Newborn , Liver Neoplasms/complications , Liver Neoplasms/secondary , Male , Neoplasm Staging , Neuroblastoma/drug therapy , Neuroblastoma/pathology
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