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Biomedical subjects

R S Young

Publications and source records attributed to R S Young.

At least 19 recordsLinked to original sources
PubMed1992

Hypoxia increases extracellular concentrations of excitatory and inhibitory neurotransmitters in subsequently induced seizure: in vivo microdialysis study in the rabbit.

It is uncertain whether a brief hypoxic exposure exerts long lasting effects on central nervous system amino acid neurotransmission. The purpose of this study was to test the hypothesis that a short period of hypoxia would affect release of excitatory and inhibitory amino acids during subsequent bicuculline-induced seizure. Utilizing in vivo microdialysis in cerebral cortex of rabbits, we observed no significant increase in extracellular fluid (ECF) concentrations of the excitatory amino acids, glutamate and aspartate, or the inhibitory amino acids, GABA and taurine, during a 30-min exposure to hypoxia (FiO2 = 0.08). In addition, there was no significant change in these amino acids during uncomplicated seizure. However, when seizure was complicated by a preceding period of hypoxia, there was a marked and progressive rise in both excitatory and inhibitory amino acids in ECF. We conclude that a short period of hypoxia, which itself does not cause changes in ECF concentrations of excitatory amino acids, may nonetheless contribute to neuronal injury by altering the levels of ECF amino acids during a subsequent insult.

Animals↗
PubMed1992

Hyperglycemia and the rate of lactic acid accumulation during cerebral ischemia in developing animals: in vivo proton MRS study.

During cerebral ischemia, hyperglycemia has a deleterious effect upon the adult brain but not the neonatal brain. This phenomenon may be related to the fact that hyperglycemia in adult animals subjected to cerebral ischemia raises the ischemic accumulation of lactate by as much as 10-fold. The purpose of this study was to determine whether hyperglycemia during cerebral ischemia produces a similar increase in the rate of lactic acid accumulation in developing animals. Data from in vivo proton magnetic resonance spectroscopic experiments showed that blood glucose concentration did not affect the rate of lactic acid accumulation during cerebral ischemia in either the neonatal dog or juvenile rabbit. The lack of increase in the ischemic rate of lactic acid accumulation during hyperglycemia in the developing animal contrasts sharply with the marked effect of blood glucose concentration upon the rate of lactic acid accumulation in the adult animal. Differences in the total amount of lactic acid formed and the rate at which it is accumulated may contribute, in part, to the greater tolerance of the young animal to cerebral ischemia.

Aging↗
PubMed1991

Effects of glutamate, quisqualate, and N-methyl-D-aspartate in neonatal brain.

The intracerebral injection of the excitotoxins, glutamate (GLU), or its analogues, quisqualic acid (QA) and N-methyl-D-aspartate (NMDA), produces neuropathologic changes which resemble those induced by hypoxic-ischemic injury. We employed proton magnetic resonance spectroscopy to investigate the acute biochemical changes which follow injection of these excitotoxins in the neonatal rat brain. Aspartate and GLU increased in animals injected with GLU or NMDA. Alanine, glycine, and taurine increased with all three excitotoxins. There was no decrease in phosphocreatine (PCr) or glucose and only a modest increase in lactate after excitotoxin injection, but there was substantial change in these metabolites after hypoxia. GABA rose only after hypoxic-ischemic injury. Although NMDA and QA produced morphological changes which resembled those following hypoxic-ischemic injury, the effect of these excitotoxins on levels of PCr, glucose, and excitatory and inhibitory amino acids was considerably different.

Amino Acids↗
PubMed1991

Preferential utilization of lactate in neonatal dog brain: in vivo and in vitro proton NMR study.

In vivo proton nuclear magnetic resonance spectroscopy was utilized to determine whether lactate is preferentially utilized as metabolic fuel by the neonatal dog brain. The data showed that during lactate influx, metabolism of lactate could account for most of the fuel needed for oxidative metabolism. The in vivo nuclear magnetic resonance measurements were corroborated by conventional arteriovenous determinations which showed steep decline of arteriovenous difference of glucose and sharp increase in arteriovenous difference of lactate during lactate infusion.

Animals↗
PubMed1991

Brain energy state and lactate metabolism during status epilepticus in the neonatal dog: in vivo 31P and 1H nuclear magnetic resonance study.

The purpose of these experiments was to determine whether flurothyl-induced status epilepticus causes progressive decline of brain high-energy phosphates and progressive increase in brain lactate in neonatal dogs who are paralyzed and oxygenated. In vivo 31P nuclear magnetic resonance spectroscopic measurements showed that the fall in brain pH occurred early in the course of seizure. The decline in phosphocreatine was more gradual, i.e. 50% reduction, during the 1st h of seizure. There was no reduction in ATP during the 3 h of status epilepticus. In vivo 1H nuclear magnetic resonance measurement of brain lactate disclosed a steep rise that stabilized by 60 min. Brain and blood lactate were closely related during the initial phase of seizure, suggesting rapid efflux of lactate from brain or systemic production of lactate. Blood lactate exceeded brain lactate after 1 h of status epilepticus. The new steady state for cerebral phosphocreatine and lactate during status epilepticus was achieved much more slowly during neonatal status epilepticus than has been reported during status epilepticus in the adult experimental animal. The lack of change in ATP during 3 h of seizure indicates that brain energy state is not radically altered during prolonged seizure if oxygenation is maintained.

Adenine Nucleotides↗
PubMed1991

Determination of lights that are isoluminant for both scotopic and photopic vision.

A set of lights can be defined as D isoluminant if it is simultaneously isoluminant for both photopic and scotopic vision. Methods for determining sets of D-isoluminant lights are provided. It is shown that monochromatic lights cannot be made D isoluminant with one another for most of the spectrum and that particular white lights can each be made D isoluminant with a particular monochromatic light. Rules are provided for determining D isoluminance in dichromatic and trichromatic mixtures. The potential uses and limitations of D-isoluminant stimuli are discussed.

Color Perception↗
PubMed1990

Neonatal excitotoxic brain injury. Physiologic, metabolic, and pathologic findings.

The mechanism of brain injury caused by excitotoxins has been explored in detail in the adult, but not the developing animal. To better define the cerebral physiologic. metabolic and pathological effects of excitotoxic damage, quisqualic acid (QA), a glutamate analogue, was injected into the parahippocampal region of the neonatal rat. Electroencephalographic monitoring showed intermittent paroxysmal discharges which persisted for more than 24 h. Metabolic alterations were consistent with disruption of membrane function with a decrease in n-acetyl aspartate and a rise in acetate. Neuropathologic examination disclosed neuronal necrosis which was maximal in the medial CA1 and hilar areas. QA produces a unique pattern of physiologic, metabolic, and pathologic alteration in the neonatal rat brain which differs from that produced by hypoxic-ischemic injury.

Animals↗
PubMed1989

Assignment of the gene for complete X-linked congenital stationary night blindness (CSNB1) to Xp11.3.

X-linked congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder characterized by a presumptive defect of neurotransmission between the photoreceptor and bipolar cells. Carriers are not clinically detectable. A new classification for CSNB includes a complete type, which lacks rod function by electroretinography and dark adaptometry, and an incomplete type, which shows some rod function on scotopic testing. The refraction in the complete CSNB patients ranges from mild to severe myopia; the incomplete ranges from moderate hyperopia to moderate myopia. To map the gene responsible for this disease, we studied eight multigeneration families, seven with complete CSNB (CSNB1) and one with incomplete CSNB, by linkage analysis using 17 polymorphic X-chromosome markers. We found tight genetic linkage between CSNB1 and an Xp11.3 DNA polymorphic site, DXS7, in seven families with CSNB1 (LOD 7.35 at theta = 0). No recombinations to CSNB1 were found with marker loci DXS7 and DXS14. The result with DXS14 may be due to the small number of scored meioses (10). No linkage could be shown with Xq loci PGK, DXYS1, DXS52, and DXS15. Pairwise linkage analysis maps the gene for CSNB1 at Xp11.3 and suggests that the CSNB1 locus is distal to another Xp11 marker, TIMP, and proximal to the OTC locus. Five-point analysis on the eight families supported the order DXS7-CSNB1-TIMP-DXS225-DXS14. The odds in favor of this order were 9863:1. Removal of the family with incomplete CSNB (F21) revealed two most favored orders, DXS7-CSNB1-TIMP-DXS255-DXS14 and CSNB1-DXS7-TIMP-DXS255-DXS14. Heterogeneity testing using the CSNB1-M27 beta and CSNB1-TIMP linkage data (DXS7 was not informative in F21) was not significant to support evidence of genetic heterogeneity (P = 0.155 and 0.160, respectively).

Alleles↗
PubMed1989

Isoflurane for refractory status epilepticus: a clinical series.

General anesthesia has been recommended to control convulsive status epilepticus that is refractory to conventional anticonvulsant therapy. Halothane has been the recommended agent, but without experimental justification. Isoflurane, which has no reported organ toxicity and produces electrographic suppression at clinically useful concentrations in normal humans, should be a better volatile anesthetic for this purpose. The efficacy and safety of isoflurane administered to control convulsive status epilepticus were assessed on 11 occasions in nine patients in seven North American hospitals. Isoflurane, administered for 1-55 h, stopped seizures in all patients and was able to be titrated to produce burst-suppression patterns on electroencephalograms. Blood pressure support with iv fluids and/or pressor infusions was required in all of the patients. Seizures resumed upon discontinuation of isoflurane on eight of 11 occasions. Six of the nine patients died. The three survivors sustained cognitive deficits. In one patient urine fluoride concentrations were elevated, although not to nephrotoxic levels. These cases suggest that isoflurane 1) is an effective, rapidly titratable anticonvulsant; 2) does not reverse underlying causes of the refractory seizures; and 3) usually necessitates hemodynamic support with fluids and/or pressors. Isoflurane may be administered for seizures, but only when iv agents in anesthetic doses are ineffective or produce unacceptable side effects.

Adolescent↗
PubMed1989

A comparative study of minoxidil-induced myocardial lesions in beagle dogs and miniature swine.

Minoxidil, a long-acting vasodilating antihypertensive agent, reduces arterial blood pressure by a direct action on arteriolar smooth muscle. The present studies examined the gross anatomic, histologic and ultrastructural myocardial alterations produced by 2 daily doses of minoxidil in beagle dogs (0.5, 1, or 3 mg/kg) and miniature swine (1, 3, or 10 mg/kg). Both myocardial necroses and hemorrhages were observed in dogs and pigs 24 hr after the last dose of minoxidil. In both species, the necroses were most frequent in the left ventricular papillary muscles, particularly the posterior one, but were less severe in swine. An ischemic origin of the necroses was suggested by the location of the lesions and by the pharmacologic effects of minoxidil. Gross epicardial or endocardial hemorrhages involving the atria and, to a lesser extent, the ventricles were observed in both species but were more severe in dogs. The atrial lesions were manifested grossly by diffuse redness and microscopically by interstitial edema, extravasated erythrocytes and infiltration of mononuclear cells. Hemorrhages, occurring on the epicardial surfaces, were often associated with lesions that involved small arteries having 3-6 layers of medial smooth muscle cells and were characterized by endothelial injury, intramural accumulations of erythrocytes and platelets, periadventitial hemorrhage, fibrin deposits and an inflammatory cell reaction. These lesions preferentially involved the right atrium in dogs and the left atrium in pigs. Pretreatment of beagle dogs with pyribenzamine (3 doses of 6 mg/kg every 8 hr), cimetidine (3 doses of 15 mg/kg every 8 hr), or both, had no effect on the incidence or severity of minoxidil-induced hemorrhagic lesions. The hemorrhagic lesions may be caused by overstretching of the vascular walls due to excessive, prolonged vasodilatation.

Animals↗
PubMed1989

The effect of diazepam on neonatal seizure: in vivo 31P and 1H NMR study.

It is assumed that when anticonvulsants arrest seizure, there is rapid return of brain high energy phosphates and brain lactate to control values. To test this hypothesis, diazepam was administered to neonatal dogs during flurothyl-induced seizure. In vivo 31P nuclear magnetic resonance spectroscopy disclosed that diazepam quickly arrested electrographic seizure and restored brain phosphocreatine and inorganic phosphate to baseline values. In contrast, in vivo 1H nuclear magnetic resonance spectroscopic measurements showed that arrest of seizure with diazepam did not return brain lactate to control values. The sustained increase in cerebral blood flow and prolonged elevation of brain lactate, acetate, valine, and succinate in the postictal period indicate that metabolic recovery of the brain occurs over an extended period of time after the normalization of EEG, phosphocreatine, and brain pH.

Acetates↗
PubMed1989

Oscillatory potentials of X-linked carriers of congenital stationary night blindness.

ERG oscillatory potentials (OPs) were recorded from obligate carriers of CSNB and from age-matched normal subjects. The OPs were recorded under four stimulus conditions and were analyzed in the time and frequency domains. The results, first of all, provide confirmation of the previous report that the OP amplitude is reduced in carriers. Second, the results show that, of four stimulus conditions examined, the best condition for discriminating the carriers and normal subjects was when the flash was blue and the eye was dark-adapted. Third, the results show that, in the frequency domain, optimal discrimination occurs when examining the power content of the OP at a center frequency of about 130 Hz using a 70 Hz bandwidth window. In the time domain, optimal discrimination occurs when examining the amplitude of the third peak of the response.

Electroretinography↗
PubMed1988

Effect of pretreatment with ICRF-187 on the total cumulative dose of doxorubicin tolerated by beagle dogs.

Studies were made of the influence of ICRF-187 on the functional and morphological effects of very large cumulative doses of doxorubicin given over a prolonged period of time. Adult beagles of either sex (6.2-11.6 kg) were given doxorubicin (1.75 mg/kg i.v.) either alone or 15 min after ICRF-187 (25 mg/kg, i.v.) at 3-week intervals. Control dogs received ICRF-187 (25 mg/kg, i.v.) or 0.9% saline without doxorubicin. Of eight animals receiving doxorubicin alone, five died; two after a total dose of 12.25 mg/kg and three after 14 mg/kg; three others were in poor condition at the time of euthanasia after 14 mg/kg. Of eight animals receiving both ICRF-187 and doxorubicin, four died; two after 35 mg/kg, one after 43.75 mg/kg, and one after 52.5 mg/kg; two other dogs were euthanized after 43.75 mg/kg because of difficulties encountered in giving i.v. injections, and two dogs survived a total dose of 52.5 mg/kg. All control dogs survived. None of the treatment or control groups developed consistent echocardiographic changes or alterations in mean arterial pressure. By 300 days after onset of treatment, dogs given ICRF-187 and doxorubicin developed significant prolongation of the PQ interval; by 550 days, surviving dogs in this group developed ventricular premature contractions. Each animal receiving doxorubicin alone had severe myocardial lesions (lesion score 3+). Of the animals given ICRF-187 and doxorubicin, one that received 35 mg/kg doxorubicin had no lesions; of four given 43.75 mg/kg, three had no lesions and one had minimal lesions (lesion score 1+); of three given 52.5 mg/kg, one had minimal (lesion score 1+), and two had moderate (lesion score 2+) lesions. Control animals had no myocardial lesions. Thus, ICRF-187 provided significant protection when administered with doxorubicin over a period of 90 weeks, and made it possible to give doses of doxorubicin which otherwise would have been lethal.

Animals↗
PubMed1988

Effect of adaptation and wavelength on the power spectrum of human oscillatory potentials.

Oscillatory potentials were recorded from four adult subjects under dark- and light-adapted conditions with photopically balanced red and blue flashes. The responses between 80 and 200 Hz were analyzed by means of a Fast Fourier transform program. The results show a robust change in the power--but not in the frequency composition--with the different stimulus conditions. We suggest that an analysis of the total power within this frequency band may provide a quantitative way of evaluating the duplex nature of the oscillatory potentials.

Adaptation, Physiological↗
PubMed1988

Jaw and skull changes in neurofibromatosis.

Thirty-eight patients with neurofibromatosis were examined clinically and radiographically for manifestations of the disease in the head and neck region. Ninety-two percent of the sample had at least one intraoral or radiographic sign of the disease. This suggests that the incidence of jaw and skull involvement in neurofibromatosis may be greater than previously reported in the literature.

Adolescent↗
PubMed1988

Examination of minoxidil-induced acute cardiotoxicity in miniature swine.

Minoxidil, a vasodilating antihypertensive agent, was given orally in doses of 1, 3 or 10 mg/kg to miniature swine on 2 consecutive days. Mean arterial pressure decreased and heart rate increased most consistently after the 10 mg/kg dose. However, all 3 doses of minoxidil induced myocardial hemorrhages and/or left ventricular papillary muscle necrosis within 24 h after the second dose. Necrosis, characterized by hypercontraction of muscle cells and myofibrillar damage, occurred in 1 of 8 pigs given 1 mg/kg, 3 of 13 given 3 mg/kg and 7 of 14 given 10 mg/kg of minoxidil. The pharmacological effects of minoxidil, hypotension and reflex tachycardia, probably led to ischemia and necrosis in left ventricular papillary muscles. Gross hemorrhages involving the left atrium and to a lesser extent the left ventricle were found in 4 of 8 pigs given 1 mg/kg, 9 of 13 given 3 mg/kg and 11 of 14 given 10 mg/kg of minoxidil. The atrial lesions were manifested grossly by diffuse redness and microscopically by interstitial edema, extravasation of erythrocytes and infiltration of areas around small arteries and arterioles with acute and chronic inflammatory cells. The hemmorhagic areas were concentrated along the epicardial surfaces, and to a lesser extent along the endocardial surfaces. Atrial lesions induced by minoxidil preferentially involve the left atrium in pigs and the right atrium in dogs. These differences may be related to the anatomic patterns of coronary circulation in the 2 species.

Administration, Oral↗
PubMed1988

Pretreatment with ICRF-187 allows a marked increase in the total cumulative dose of doxorubicin tolerated by beagle dogs.

To study the influence of ICRF-187 on the functional and morphological effects of very large cumulative doses of doxorubicin, adult beagle dogs were given doxorubicin (1.75 mg/kg i.v.) either alone or 15 min after ICRF-187 (25 mg/kg, i.v.) at 3-week intervals. Control dogs received ICRF-187 (25 mg/kg, i.v.) or 0.9% saline without doxorubicin. Of eight animals receiving doxorubicin alone, two died after a total dose of 12.25 mg/kg and three died after 14 mg/kg; three others were in poor condition at the time of euthanasia after 14 mg/kg. Of eight animals receiving both ICRF-187 and doxorubicin, one died after 35 mg/kg, two died after 43.75 mg/kg and one died after 52.5 mg/kg; two dogs were euthanatized after 43.75 mg/kg because of difficulties encountered in giving i.v. injections, and two dogs survived a total dose of 52.5 mg/kg. All control dogs survived. None of the treatment or control groups developed consistent echocardiographic changes or alterations in mean arterial pressure. Dogs given ICRF-187 and doxorubicin developed PQ interval prolongation after 300 days and ventricular premature beats after 500 days. Each animal receiving doxorubicin alone had severe myocardial lesions (lesion score 3+). Of the animals given ICRF-187 and doxorubicin, one that received 35 mg/kg doxorubicin had no lesions; of four given 43.75 mg/kg, three had no lesions and one had minimal lesions (lesion score 1+); of three given 52.5 mg/kg, one had minimal (lesion score 1+) and two had moderate (lesion score 2+) lesions. Control animals had no myocardial lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗