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Biomedical subjects

R Vega

Publications and source records attributed to R Vega.

At least 55 records · Page 3Linked to original sources

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↗

Recombinant interferon alfa given before and in combination with standard chemotherapy in children with acute lymphoblastic leukemia in first marrow relapse: a Pediatric Oncology Group pilot study.

Recombinant interferon alfa (rIFN-alpha) was given to 31 children with acute lymphoblastic leukemia (ALL) in first on-therapy marrow relapse as the sole treatment (30 megaunits/m2/d intravenously x 10 days) before standard four-drug reinduction and during multiagent continuation therapy (30 megaunits/m2 subcutaneously x 3 consecutive days every 3 weeks). After 10 days of rIFN-alpha, there were two partial remissions (PRs); seven additional patients had either greater than or equal to 25% reduction in the percentage of marrow blast cells or hypoplastic marrow. Two patients had progressive disease with an increase in leukocyte counts. All patients experienced influenza-like symptoms, and there were isolated instances of severe abdominal pain and personality change. Dose-limiting toxicity comprised grade III/IV transaminase elevation (two patients) and syncope with personality change (one patient). Twenty-three of 31 children (74%) subsequently achieved marrow remission using standard agents. One patient was taken off study during teniposide (VM-26) and cytarabine (ara-C) consolidation due to toxicity. Continuation therapy including rIFN-alpha pulse was well tolerated in the remaining children; only one patient required rIFN-alpha dosage reduction (for CNS toxicity). rIFN-alpha toxicity did not necessitate reductions in doses of standard chemotherapy agents or significant delays in therapy. Five patients remain in remission at 26+ to 36+ months; 13 patients relapsed in marrow, one in the meninges (7 months), and one in meninges, mediastinum, and lymph nodes (2 months). Two children were removed from study for marrow transplant. In summary, high-dose rIFN-alpha alone had a modest antileukemic effect. In contrast to the clinical experience with combined rIFN-alpha and chemotherapy in adults, rIFN-alpha given in a pulse-like manner throughout continuation therapy did not compromise the intensity of the standard chemotherapy regimen.

Adolescent↗

Phase I trial of indicine-N-oxide in children with leukemia and solid tumors: a Pediatric Oncology Group study.

A phase I trial of indicine-N-oxide was carried out in 12 children with solid tumors and in 16 with leukemia. Doses of 5, 6, and 7.5 g/m2 were given parenterally as a 15-min infusion every 3 weeks. The maximum tolerated dose in patients with solid tumors was 7.5 g/m2 and the dose-limiting toxicity was myelosuppression. In leukemia, the maximum tolerated dose was 6.0 g/m2 and hepatotoxicity was dose-limiting. Half of the children with leukemia showed elevations in transaminase levels and one child died of massive hepatic necrosis. This hepatotoxicity limits the use of indicine-N-oxide in children with leukemia. Antineoplastic activity was limited to a transient reduction in the numbers of circulating leukemic cells.

Adolescent↗

Teaching field potentials: a microcomputer simulation of the nerve action potential in a bidimensional conductor.

A computer simulation of the extracellular field potential recording of nerve activity is presented. An experimental setup composed of an oscilloscope, a nerve, a conductive surface, and a recording electrode is graphically simulated. The user may study the influence of the position of the recording electrode and of certain nerve properties (membrane potential, velocity of conduction and action potential duration), on the action potential shape. The different waves which constitute the action potential may be analyzed and their peak values plotted as a function of the independent variable (e.g. electrode distance from the nerve). Three-dimensional plots of a set of action potentials as a function of the independent variable may also be obtained. The stimulation allows the user to study the basic factors which determine the configuration of an extracellularly recorded compound nerve action potential.

Action Potentials↗

Computer program for statistical Mann-Whitney U nonparametric analysis of neuronal spike activity.

A program for neuronal activity analysis is described. The applied computational techniques are standard in the field of digital processing, but the program is particular in its field of application and mode of data selection. The program, written in Turbo Pascal for the IBM-PC and compatibles, statistically compares (Mann-Whitney U-test) two sets of graphically selected data, and establishes whether there are significant differences between them. Although the program was developed for spike frequency analysis, it can easily be adapted to perform statistical analysis of other kinds of data.

Action Potentials↗

Actions of excitatory amino acid acid agonists and antagonists on the primary afferents of the vestibular system of the axolotl (Ambystoma mexicanum).

In order to determine the nature of the transmitter in the synapse between hair cells and primary afferent fibers, both resting and evoked spike activity of vestibular system afferents were recorded. Excitatory amino acid agonists and antagonists were applied by micro perfusion. Excitatory amino acid agonists consistently increased the firing rate of these afferents. The rank order in potencies of the agonists tested was: kainate greater than or equal to quisqualate greater than D-aspartate greater than or equal to L-glutamate greater than or equal to L-aspartate greater than N-methyl D-aspartate. Blockade of synaptic transmission with high-Mg2+ and low-Ca2+ solutions did not seem to affect the responses to the excitatory amino acid agonists indicating their postsynaptic action. Excitatory amino acid antagonists inhibit both resting and physiologically evoked activity. The rank order of inhibitory potency was: kynurenate greater than L-glutamate diethyl ester greater than D,L-2-amino-4-phosphono-butyrate greater than D-alpha-amino adipate greater than D,L-2-amino-5-phosphonovalerate. These findings suggest that an amino acid-related compound may be the transmitter at this synapse. The relative potencies of agonists and antagonists tested provide evidence that the transmitter released from the hair cells' basal pole in the axolotl vestibular system interacts with postsynaptic kainic/quisqualic type receptors.

Action Potentials↗

Transitory macrophage activation in the granulomatous lesions of Mycobacterium lepraemurium-induced lepromatoid leprosy in the mouse.

A kinetic study on the evolution of granulomas that appear in the liver of NIH mice inoculated with 10(8) Mycobacterium lepraemurium by the intraperitoneal route has been performed. The liver was chosen because of its nonlymphoid histology which allowed us to visualize the appearance and maturation of the cell infiltrates generated as a consequence of the mycobacterial infection. The study analyzed both the macrophage activation within the granulomas and the fate of bacilli within the macrophage. The results showed that this mycobacteriosis induces a relatively early macrophage activation (a very likely result of a cell-mediated immune response triggered by the bacilli) that peaks between 45 and 60 days postinoculation, fades thereafter, and practically disappears several days later. Bacilli are susceptible to the microbicidal effects of activated macrophages, but when the macrophages are turned off (probably due to active suppressive mechanisms), the surviving bacilli reinitiate the infection with no further macrophage opposition. As a result, more phagocytes are attracted to the infection sites and the cell infiltrates grow steadily to become confluent, increasing the granuloma fraction and eventually replacing the liver parenchyma. The findings suggest that in murine "leprosy" infection, early immunological changes occur that enable the macrophages present in the granulomas to kill the infecting M. lepraemurium regardless of the eventual lepromatoid evolution of the granulomas. Lepromatoid granulomas in the mouse and lepromatous granulomas in man are equivalent structures in regard to their histology and bacteriology.

Animals↗

A Turbo Pascal program for on line spike data acquisition and analysis using a standard serial port.

A Turbo Pascal program for data acquisition and analysis is presented. The program detects incoming data as TTL pulses through the serial port of an IBM-PC and compatible computers and displays the instantaneous frequency plot and the interval histogram on-line. Novel features of this Pascal program are: no special hardware requirements and on-line analysis of more than one source at a time. No hardware additions to the supplied computer and easy operation make this program a valuable tool, directly useable in an IBM-PC and compatible computers.

Action Potentials↗

Is GABA an afferent transmitter in the vestibular system?

This study was undertaken to determine the possible role of GABA as an afferent transmitter in the vestibular system of the axolotl. We studied the effects of GABA, muscimol, bicuculline and picrotoxin on the spontaneous spike discharge of the afferent fibers of the sacculi lagena and anterior semicircular canal. It was found that GABA and muscimol produce a very weak excitatory effect which does not mimic either the temporal course or the amplitude of the response of vestibular afferents to physiological stimuli. The GABA antagonist bicuculline has no significant effect on these fibers, and picrotoxin partially blocks the spontaneous activity in 33% of the fibers studied. These results indicate that GABA is probably not an afferent transmitter in the vestibular system as has previously been proposed.

Afferent Pathways↗

Growth and development of children born to patients after cancer therapy.

Eighteen children born to parents who had previously received chemotherapy or radiotherapy were examined for physical health, growth, and development. The immunologic and the hematologic status of these children was also evaluated. Their ages ranged from birth to 15 years. The children had a careful history and physical examination to detect any abnormal symptoms or signs, and the parent's previous treatment was carefully documented. Four sets of parents had children while one of the parents was on active treatment (2 male and 2 female). Of the male patients, one patient's wife had a baby that was "small for gestational age" at birth and had transient failure to thrive; the other child was normal. Of the female patients, one offspring was small for gestational age at birth and the other was normal, but both continued to have failure to thrive for up to 17 months and 26 months, respectively. Ten parents procreated after being treated with chemotherapy and/or radiotherapy, to whom 14 children were born. One child was a stillbirth with multiple congenital abnormalities, and another child had trisomy 13-15 and died 6 months later. The other 12 children were normal at birth, but one child is under the 5th percentile for growth at twelve months of age. In all children studied, immune function test, complete blood count, and viral titers were considered normal for age. In our study, we found that three out of four children born to parents who were on chemotherapy had failure to thrive. Of the 14 children born to parents who conceived after being off chemotherapy, 11 were found to be normal in growth and development. These results imply that there is a high risk of complications in children born to parents who procreated while receiving chemotherapy. Further studies are needed to develop better guidelines for counseling cancer patients who want to have children.

Abnormalities, Multiple↗