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Biomedical subjects

R Vega

Publications and source records attributed to R Vega.

At least 19 recordsLinked to original sources

Cognitive and academic late effects among children previously treated for acute lymphocytic leukemia receiving chemotherapy as CNS prophylaxis.

OBJECTIVE: Examine cognitive and academic late effects among children and adolescents who had received central nervous system (CNS) prophylactic chemotherapy alone for acute lymphocytic leukemia (ALL); none had received whole brain radiation therapy (RT). METHOD: Subjects included 47 children and adolescents from 5 to 22 years of age who were treated on the same protocol and had been off treatment from 2 to 7 years at the time of assessment. RESULTS: As a group the survivors displayed generally average performance on measures of cognitive and academic abilities, although they differed from normative means on tests of nonverbal skills. Girls performed more poorly than the normative sample on nonverbal tasks, while no differences were found for boys. Age at diagnosis and time off treatment were not significantly associated with cognitive and academic functioning for survivors of this particular chemotherapy-only protocol. CONCLUSIONS: Data were interpreted to support generally modest potential late effects in specific areas for children and adolescents surviving ALL. These findings suggest a need for monitoring nonverbal cognitive skills for childhood survivors of ALL, particularly for girls.

Achievement

A microcomputer program for automated neuronal spike detection and analysis.

A system for on-line spike detection and analysis based on an IBM PC/AT compatible computer, written in TURBO PASCAL 6.0 and using commercially available analog-to-digital hardware is described here. Spikes are detected by an adaptive threshold which varies as a function of signal mean and its variability. Since the threshold value is determined automatically by the signal-to-noise ratio analysis, the user is not actively involved in controlling its level. This program has been reliably used for the detection and analysis of the spike discharge of vestibular system afferent neurons. It generates the interval-joint distribution graph, the interval histogram, the autocorrelation function, the autocorrelation histogram, and phase-space graphs, thus, providing a complete set of graphical and statistical data for the characterization of the dynamics of neuronal spike activity. Data can be exported to other software such as Excel, Sigmaplot and MatLab, for example.

Ambystoma

[Epidemiology of the osteoporotic fracture of the hip in the province of Palencia].

BACKGROUND: Hip fracture is the most severe consequence of osteoporosis. The aim of the present study was to know the incidence of osteoporotic hip fracture in the Palencia province, its direct economical consequences and characteristics associated with the origin episode. PATIENTS AND METHODS: All patients aged over 49 years who had a nontraumatic hip fracture during the second semester of 1994 and the first semester of 1995 were included in the study. An analysis of costs was performed and each patient received a questionnaire to know the circumstances associated with the episode. RESULTS: During the study period the overall incidence of hip fracture was 83/100,000 inhabitants/year, which corresponds to an adjusted incidence of 240.9/100,000 inhabitants older than 49 years (336.8 women and 120.7 men). There was an exponential growth, with peak values starting at 80 years. The female/male ratio was 2.8 and the mean age 80.8 years. Twenty-four percent of fractures occurred in institutionalized persons, with an adjusted incidence of 1,107/100,000 inhabitants/year, which corresponds to a relative risk of 13.57 (95% CI: 10.06-18.28). No significant differences were observed between trochanteric and neck fractures. Ninety-seven percent of fractures occurred after a fall, usually in the morning or afternoon (86%), with lateral direction and impact on the greater trochanter (89%). The mortality rate during admission was 5.9%. The mean cost of care during admission was 1,170,000 pesetas. CONCLUSIONS: The incidence of hip fracture in Palencia is slightly higher than the national mean, probably due to populational ageing. The risk of fracture reaches alarming proportions in the institutionalized population. The implementation of efficient preventive measures, particularly among the exposed populations, is necessary.

Accidental Falls

Histochemistry and role of nitric oxide synthase in the amphibian (Ambystoma tigrinum) inner ear.

Nicotinamide adenine dinucleotide phosphate reduced-diaphorase (NADPH-d) histochemistry was investigated in the axolotl (Ambystoma tigrinum) inner ear. Hair cells showed an intense NADPH-d reaction; afferent neurones also stained but less intensely than hair cells. Effects of NG-nitro-L-arginine (L-NOARG) on the basal discharge and mechanical responses of semicircular canal afferent neurones recorded extracellularly were also studied. L-NOARG (1 mu M) diminished the basal discharge and the response of afferent neurones to sinusoidal mechanical stimuli to 45 +/- 6.4% and 65 +/- 5.3% (mean +/- SEM) of control value, respectively. These findings suggest that production of nitric oxide (NO) by hair cells and probably also by afferent neurones contributes to the basal discharge and the response of afferent neurones to mechanical stimuli.

Ambystoma

Antagonism of glutamate receptors by a chromatographic fraction from the exudate of the sea anemone Phyllactis flosculifera.

In the search for new glutamate antagonists it seems promising to characterize the effects of venom from invertebrates that prey mainly on crustaceans. In this work, the exudate of the sea anemone Phyllactis flosculifera was used as a source of this type of compound. The action of chromatographic fraction D from P. flosculifera was tested upon microion-tophoretically evoked glutamate responses in intracellular recordings from central neurons of the land snail Zachrysia guanensis. Bath application of fraction D (2-8 mg/ml, n = 13) diminished both the excitatory and the inhibitory components of glutamate agonists in Z. guanensis neurons; this action was dose-dependent and partially reversible. Fraction D actions were also tested in the multiunit spontaneous and mechanically evoked responses of the glutamatergic junction between hair cells and afferent neurons of the axolotl Ambystoma tigrinum. Pressure ejection of fraction D in concentrations ranging from 0.5 to 2 mg/ml (n = 9) decreased the spontaneous and mechanically evoked activity of semicircular canal afferent neurons and the responses evoked by kainic acid and alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid. This action was also dose-dependent and partially reversible. These results indicate that fraction D acts as a glutamate receptor antagonist in snail and amphibian neurons. Further studies are required to characterize the active compounds responsible for this action and its specificity upon the subtypes of glutamate receptors.

Ambystoma

Transcriptional control of a nuclear gene encoding a mitochondrial fatty acid oxidation enzyme in transgenic mice: role for nuclear receptors in cardiac and brown adipose expression.

Expression of the gene encoding medium-chain acyl coenzyme A dehydrogenase (MCAD), a nuclearly encoded mitochondrial fatty acid beta-oxidation enzyme, is regulated in parallel with fatty acid oxidation rates among tissues and during development. We have shown previously that the human MCAD gene promoter contains a pleiotropic element (nuclear receptor response element [NRRE-1]) that confers transcriptional activation or repression by members of the nuclear receptor superfamily. Mice transgenic for human MCAD gene promoter fragments fused to a chloramphenicol acetyltransferase gene reporter were produced and characterized to evaluate the role of NRRE-1 and other promoter elements in the transcriptional control of the MCAD gene in vivo. Expression of the full-length MCAD promoter-chloramphenicol acetyltransferase transgene (MCADCAT.371) paralleled the known tissue-specific differences in mitochondrial beta-oxidation rates and MCAD expression. MCADCAT.371 transcripts were abundant in heart tissue and brown adipose tissue, tissues with high-level MCAD expression. During perinatal cardiac developmental stages, expression of the MCADCAT.371 transgene paralleled mouse MCAD mRNA levels. In contrast, expression of a mutant MCADCAT transgene, which lacked NRRE-1 (MCADCATdeltaNRRE-1), was not enriched in heart or brown adipose tissue and did not exhibit appropriate postnatal induction in the developing heart. Transient-transfection studies with MCAD promoter-luciferase constructs containing normal or mutant NRRE-1 sequences demonstrated that the nuclear receptor binding sequences within NRRE-1 are necessary for high-level transcriptional activity in primary rat cardiocytes. Electrophoretic mobility shift assays demonstrated that NRRE-1 was bound by several cardiac and brown adipose nuclear proteins and that these interactions required the NRRE-1 receptor binding hexamer sequences. Antibody supershift studies identified the orphan nuclear receptor COUP-TF as one of the endogenous cardiac proteins which bound NRRE-1. These results dictate an important role for nuclear receptors in the transcriptional control of a nuclear gene encoding a mitochondrial fatty acid oxidation enzyme and identify a gene regulatory pathway involved in cardiac energy metabolism.

Acyl-CoA Dehydrogenase

NMDA-mediated potentiation of the afferent synapse in the inner ear.

In an isolated vestibular organ preparation from the axolotl (Ambystoma tigrinum), glycine (10-0.01 microM) perfusion had no effect in the resting control condition, but significantly modified the response of afferent fibres to mechanical stimuli, producing a slowly increasing discharge rate during sinusoidal mechanical stimulation periods. This action was dependent upon the stimulus duration and was antagonized by 7-chloro-kynurenic acid (7-ClKyn), 2-amino-5-phosphonopentanoic acid (AP5), N-allyl-nor-metazocina (MK-801) and extracellular magnesium. These results indicate that glycine modulates the afferent synapse in the vestibular organ, and that, NMDA receptors codify long lasting mechanical stimuli.

2-Amino-5-phosphonovalerate

Evidence for NMDA receptor in the afferent synaptic transmission of the vestibular system.

This study aimed to define the pharmacology and physiological role of the N-methyl-D-aspartate (NMDA) receptor in the synapse between the hair cells and primary afferent neurons in the vestibular system. The spontaneous and mechanically evoked spike discharges of vestibular nerve fibers were extracellularly recorded in isolated inner ear from the axolotl (Ambystoma tigrinum). Pressure ejection of NMDA (10(-6) to 10(-3) M) elicited a dose-dependent increase of the basal spike discharge from the vestibular nerve fibers. Extracellular magnesium antagonized the NMDA effect in a dose-dependent manner. D(-)-2-amino-5-phosphonovaleric acid (AP5, 10(-5) to 10(-3) M) and 7-chloro-kynurenic acid (7ClKyn, 10(-6) to 10(-3) M) inhibited the basal activity of the vestibular nerve fibers. 7ClKyn also diminished the responses elicited by the mechanical stimulation of the preparation. Glycine (10(-9) to 10(-6) M) applied by bath substitution enhanced the NMDA response, and the glycine agonist D-serine partially reversed the 7ClKyn inhibitory action. These results suggest that NMDA receptors participate in the generation of the basal spike discharge of vestibular system primary afferent neurons, but its activation is not critical for the response to brief mechanical stimuli.

2-Amino-5-phosphonovalerate

Baromedicine today--rational uses of hyperbaric oxygen therapy.

Compressed air, and more recently hyperbaric oxygen, have been used and misused in medical treatment for more than 300 years. Advances in physiology have led to rational protocols for hyperbaric oxygen use. Hyperbaric oxygen will enhance wound healing by fibroblast and capillary proliferation, suppress infection, reduce edema, reverse CNS damage from carbon monoxide and cyanide poisoning, and reduce clostridial alpha toxins. Monoplace and multiplace chambers are used for treatment during which EKG and oxygen tissue monitoring, as well as hemodynamic and respiratory support, can be continued, iatrogenic air embolism and diving decompression sickness demand immediate treatment. Investigative uses of adjunct therapy for several other clinical problems include treatment of MS, acute spinal cord injuries, and acute MI. Specific indications agreed on by the Undersea and Hyperbaric Medicine Society are recognized by most third-party payers including Medicare, Champus, and HMSA. Hyperbaric medicine remains a fertile area for basic physiologic investigation and outcomes research.

Barotrauma

Progress in developing improved programs for pulsed field agarose gel electrophoresis of DNA.

Details are described here for using a rotating gel to perform pulsed field agarose gel electrophoresis (PFGE) with programmable control of the following variables: magnitude of the electrical field, polarity of the electrical field, temperature of the gel and position of the rotating disk upon which the agarose gel rests. By use of this procedure for programmable control, modes of PFGE have been explored that have the following characteristics: (i) resolution by DNA length is completely lost for DNA shorter than a critical length that increases as the pulse times increase, and (ii) resolution by DNA length is enhanced for longer DNAs that are shorter than a second critical length. This window of resolution can be moved to the position of the 2-6 Mb chromosomes of Schizosaccharomyces pombe.

DNA

Streptomycin blocks the afferent synapse of the isolated semicircular canals of the frog.

This study aimed to define the acute electrophysiological effects of the perilymphatic perfusion of streptomycin in the sensory apparatus of the semicircular canals of the frog. The ampullary DC potential, the vestibular nerve multiunit discharge, the nerve DC potential and the unitary EPSP activity were recorded in isolated semicircular canals of the frog (Rana esculenta L). The results demonstrated that perilymphatic microperfusion of streptomycin (0.1, 0.3, 1 and 3 mM) reduced both resting and mechanically evoked afferent discharge, while the response of the hair cells remains unchanged. Intracellular recordings from single afferent axons showed that the reduction of the afferent discharge was mainly due to a reduction of the amplitude, but not the frequency, of the EPSPs. These results indicate that streptomycin, when applied in the fluid bathing the synaptic pole of the sensory cells, can act as an antagonist of the vestibular afferent transmitter at the postsynaptic level.

Afferent Pathways

Peritoneal dialysis efficiency in CAPD patients in treatment with rHuEPO.

Possible modifications in peritoneal behaviour that can be caused by erythropoietin (EPO) treatment and/or correction of anemia in the ultrafiltration and peritoneal diffusion were studied in 24 CAPD patients. The evolution of the patients on the medium run was also studied. The dialysate to plasma ratio, the peritoneal clearance and the mass transfer coefficient of urea and creatinine and the ultrafiltration volume were studied, baseline, after reaching the hemoglobin target, and after eight months of treatment. The group of patients developed a decrease in the dialysate to plasma ratio and in the peritoneal clearance of creatinine. After evaluating the effects of the hemoglobin and the hematocrit, we found a decrease in the dialysate to plasma ratio of urea and creatinine, and in the peritoneal clearance of creatinine. A decrease was also found in the mass transfer coefficients of urea and creatinine. An increase in the ultrafiltration was also found in the patients with hemoglobin levels higher or equal to 11 g/dl. Those changes are reversible after turning the hemoglobin levels back to levels lower than 11 g/dl.

Adult

Streptomycin blocks the postsynaptic effects of excitatory amino acids on the vestibular system primary afferents.

It has been suggested that streptomycin might be an antagonist of the glutamate receptors, and that it selectively blocks quisqualic acid receptors. We studied whether streptomycin blocks the responses to excitatory amino acid agonists on the vestibular system primary afferents, and if it allows us to differentiate between kainate (KA) and quisqualate (QA) receptor mediated responses. The experiments were performed in the axolotl (Ambystoma tigrinum). Intra- and extracellular records of the electrical activity of semicircular canal afferent fibers were obtained. Drugs were applied by pressure ejection in volumes of 20 microliters in a 10 ml bath. Streptomycin (0.01-10 mM), induced a dose dependent reversible inhibition of the basal spike discharge of the afferent fibers. This coincided with a reduction in the amplitude of excitatory postsynaptic potentials (EPSP) recorded intracellularly in the afferent fibers. Streptomycin also blocked the excitatory action produced by KA and QA; increasing concentrations of streptomycin produced a rightward shift in the concentration-response curves for both KA and QA. This action persisted even in a high Mg2+ (10 mM), low Ca2+ (0.09 mM) Ringer solution, indicating its postsynaptic nature. These results show that streptomycin might be a non-selective excitatory amino acid (EAA) receptor antagonist.

Ambystoma

High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: a Pediatric Oncology Group study.

In June 1984, the Pediatric Oncology Group (POG) initiated a pilot study (8498) using high-dose cytarabine (HdA; 3 g/m2) for intensification of early therapy in childhood acute myelogenous leukemia (AML) (group I). Remission induction therapy consisted of two courses of daunorubicin, cytarabine (Ara-C), and thioguanine (DAT). Postremission therapy consisted of four sequential courses, each consisting of (1) four doses of HdA (HdA4) followed by asparaginase (L-Asp), (2) etoposide (VP) plus azacytidine (Az), (3) prednisone, vincristine, methotrexate, and mercaptopurine (POMP), and (4) Ara-C daily for 5 days by continuous infusion. Six doses of intrathecal Ara-C were given for CNS prophylaxis. In December 1986, the protocol was amended (group II) to substitute six doses of HdA (HdA6) for the second DAT (two + five) induction course; postinduction, a single course of HdA6 was given instead of four HdA/L-Asp courses, and the remainder of the therapy was unchanged. One hundred forty group I patients and 145 group II patients were assessable. The two groups were similar with regard to clinical prognostic groups. No significant differences were noted in the two groups with regard to remission induction (85% [SE = 2%] in each group), induction deaths (6.5% v 7.0%), or deaths in remission (one in each group). Cerebellar toxicity was reported in three patients in group II (with HdA6) but none in group I (HdA4). At present, patients who received HdA6 (group II) had higher event-free survival than patients in group I (EFS at 3 years, 34% [SE = 11%] v 29% [SE = 4%]), and disease-free survival (DFS at 3 years, 42% [SE = 14%] v 34% [SE = 4%]), but the differences were not statistically significant. In both groups, children less than 2 years and those with WBCs less than 100,000/microL had significantly better outcome (EFS of 55% [SE = 10%] and 36% [SE = 5%] at 3 years, respectively) than children greater than or equal to 2 years and those with WBCs greater than or equal to 100,000/microL (EFS of 27% [SE = 5%] and 20% [SE = 9%] at 3 years, respectively.

Adolescent