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Biomedical subjects

D L Armstrong

Publications and source records attributed to D L Armstrong.

At least 109 records · Page 6Linked to original sources

Neuropathologic findings in short-term survivors of intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) occurs in 31% to 43% of infants weighing less than 1500 g. Intraventricular hemorrhage is rarely an isolated lesion at autopsy. To document associated cerebral abnormality, 24 brains of infants with a diagnosis of IVH and who survived for at least one week were examined. The diagnosis was verified in 20 infants. Choroid plexus hemorrhage and brain calcification had been misdiagnosed as IVH in two infants and in two other infants, IVH was not evident at autopsy. Eleven infants (46%) had choroid plexus hemorrhage. Twenty-two infants (92%) had additional cerebral abnormalities: periventricular leukomalacia, brainstem necrosis, hydrocephalus, or cerebellar necrosis. This study demonstrates that IVH is rarely an isolated abnormality in the preterm infant brain. The associated brain lesions should be considered in attempts to prevent or treat IVH and their presence should be suspected during clinical assessment of survivors.

Brain↗

Modulation of cerebellar granule cell activity by iontophoretic application of serotonergic agents.

Serotonergic fibers have been identified within the granule cell layer of the cerebellar cortex; however, their functional significance has not been identified. In this study the effect of serotonin on granule cell spontaneous activity was determined in the rat cerebellum. Of the 136 granule cells tested, 44.8% displayed a decrease in firing rate, 21.3% increased firing rate and 33.8% were not affected. The serotonin-induced changes in activity were not blocked by bicuculline or methysergide. The serotonin agonist 1,3 (trifluoromethylphenyl) piperazine mimicked the serotonin-induced suppressive response. Iontophoretically applied serotonin was also found to modulate GABA-induced suppression of granule cell activity. The variable effects of serotonin on spontaneous activity suggests the presence of more than one type of serotonergic receptor in the cerebellar granule cell layer.

Animals↗

The effects of trimethyltin on the Ca+2, Mg+2 and Ca+2 + Mg+2-dependent ATPases of human neuroblastoma GM 3320.

Data presented here indicate neuroblastoma GM 3320 tissue homogenates exhibit ouabain insensitive Ca+2-dependent, Mg+2-independent, Mg+2-dependent, Ca+2-independent and Ca+2 + Mg+2-dependent ATPase activities. Inclusion of trimethyltin in homogenate preparations of these cells appears to discriminate between these various ATPase activities. At low concentrations (25 microM), trimethyltin preferentially stimulated the Ca+2-dependent, Mg+2-independent ATPase activity while inhibiting the Ca+2 + Mg+2-ATPase activity approximately 70%. At 75 microM trimethyltin, the Ca+2 + Mg+2-dependent ATPase activity is inhibited greater than 95% while the Ca+2-dependent, Mg+2-independent activity is essentially unchanged from control activity and the Mg+2-dependent, Ca+2-independent activity is inhibited approximately 50%. At concentrations greater than 75 microM, trimethyltin significantly inhibits the Ca+2-dependent, Mg+2-independent ATPase activity. Thus, at trimethyltin concentrations of 50-75 microM, preferential inhibition of the Mg+2-dependent, Ca+2-independent and Ca+2 + Mg+2-dependent ATPase activities of neuroblastoma GM 3320 is achieved.

Adenosine Triphosphatases↗

Yohimbine hydrochloride reversal of ketamine hydrochloride and xylazine hydrochloride immobilization of Bengal tigers and effects on hematology and serum chemistries.

Six bengal tigers (Panthera tigris tigris) were immobilized five times at 2-wk intervals with ketamine hydrochloride (ketamine) and xylazine hydrochloride (xylazine) mixtures at different dose levels. Hematology and serum chemistry analyses on blood samples collected at each immobilization remained normal during the study. There were acute changes in hematocrit, chloride, potassium, glucose, and bilirubin as a function of xylazine dose level. The effect of yohimbine hydrochloride (yohimbine) on the depth and duration of immobilization was evaluated in a crossover design with every animal serving as its own control at each dose. Administration of yohimbine resulted in recovery of the animals within 4-8 min in contrast to greater than 60 min with no yohimbine treatment. There were no adverse effects noted with the yohimbine treatment and the tigers did not exhibit a relapse over the next 24 hr. Yohimbine at a dose of 5-15 mg per adult tiger provided effective reversal of 50-150 mg of xylazine per tiger.

Animals↗

Reduction in incidence of periventricular, intraventricular hemorrhages in hypertensive newborn beagles pretreated with phenobarbital.

Periventricular and intraventricular intracerebral hemorrhages occur frequently in premature newborns and are markers for, or contribute significantly to, neurologic morbidity in survivors. Hemorrhages are hypothesized to result from rapid fluctuations in cerebral perfusion pressure and/or cerebral blood flow. Phenobarbital sodium has been given to premature infants in anticonvulsant dosages in attempts to prevent hemorrhages, but its efficacy in clinical studies has been disputed. In this study, in the 24 to 72-hour-old newborn beagle, an animal model for periventricular and intraventricular intracerebral hemorrhage, phenobarbital sodium was administered to obtain anticonvulsant serum levels prior to phenylephrine-induced hypertensive insult. None of the animals was hypoxic or hypercarbic. Resulting hypertensive systemic mean arterial BPs were 99 +/- 8 mm Hg in the 15 control pups and 93 +/- 15 mm Hg in the 15 phenobarbital sodium-treated pups (not statistically significantly different). The duration of the hypertension was the same in both groups. Phenobarbital caused a significant decrease in mean arterial BP in the treated group just after its administration (P less than .05). Six of the 15 control pups (40%) and one of the 15 treated pups (7%) demonstrated macroscopic and microscopic periventricular and intraventricular hemorrhage (P less than .05, chi 2, Yates correction). Thus, in nonasphyxiated newborn beagles, phenobarbital sodium significantly reduced the incidence of hemorrhage after hypertensive insult.

Animals↗

Dendritic atrophy in children with Down's syndrome.

Dendritic branching was evaluated in the visual cortex of 8 children with Down's syndrome and 10 controls, ranging in age from 4 months to 7 years and divided into infantile, late-infantile, and juvenile groups. Camera lucida drawings of Golgi-impregnated neurons were used for examining the following dendritic aspects: dendritic intersections as a function of distance from the cell body, point of maximum dendritic branching, number of branch orders, total number of branch segments, and total dendritic length. The number of intersections and the total dendritic length were above normal in the infantile period (6 months old or less) and dropped steadily to significantly below normal in the juvenile group (older than 2 years). These reductions contrasted with expanding dendritic arborization in normal children. The results suggest that the dendritic tree atrophies in early childhood in Down's syndrome.

Child, Preschool↗

Isolation of glomeruli from areas of bovine cerebellum and comparison of [3H]serotonin uptake.

A method for bulk preparation of glomerular particles from subdivisions of the bovine cerebellum is presented. This method represents a modification of that previously reported by Hajos et al. [8], which increases the yield of glomerular protein by five-fold (5.5 mg/g wet wt) without compromising structural integrity or homogeneity. In addition, it offers the advantage of allowing one to study intraregional variations in the metabolic properties of cerebellar glomeruli. [3H]Serotonin (5-HT) uptake was measured in this preparation and it was demonstrated that glomeruli possess an active high affinity mechanism for this substrate. Comparison of [3H]5-HT uptake by glomeruli isolated from the cerebellar cortices of the lateral hemispheres and vermis revealed no differences in their kinetic properties.

Animals↗

Direct effects of androgens on lateral hypothalamic neuronal activity in the male rat: I. A microiontophoretic study.

Unit neuronal activity in the lateral hypothalamic-medial forebrain bundle region (LHA-MFB) of the male rat is modified following an increase of plasma testosterone level. In order to determine possible direct action of hormones on LHA-MFB neurons, unit discharge frequencies were recorded during local microiontophoresis of testosterone and estradiol, and electroosmotic application of cholesterol. Thirteen cells did not respond, 9 were nonspecifically depressed by all the steroids tested, 13 were excited by both sex-steroids, and 11 were specifically activated by testosterone. The short latencies of the responses suggest a direct effect of steroids on the plasma membrane sites.

Action Potentials↗

Rapid correction of severe hyponatremia in the rat: histopathological changes in the brain.

The purpose of the present studies was to examine the effects of rapid correction of severe hyponatremia (serum sodium less than 120 meq/liter) either to mildly hyponatremic levels (serum sodium = 130 meq/liter) or to normonatremic levels (serum sodium = 150 meq/liter) on the brain histology of rats. In group I, 13% of the rats revealed brain lesions following correction to mildly hyponatremic levels by the administration of 855 mM NaCl. All the rats (100%) in group II had brain lesions following correction to normonatremic levels by 24 h of water restriction. Similarly, all the rats in group III showed brain lesions following correction to normonatremic levels by the administration of 855 mM NaCl. Severe hyponatremia by itself did not cause any brain lesions in another group. We conclude that rapid correction of severe hyponatremia to mildly hyponatremic levels by the administration of 855 mM NaCl does not cause significant brain lesions. On the other hand, rapid correction to normonatremic levels either by water restriction or by the administration of 855 mM NaCl results in significant brain lesions.

Animals↗

Dendritic development in human occipital cortical neurons.

Using quantitative techniques on rapid Golgi impregnations, the dendrites from neurons of visual cortex from 14 infants ranging in age from 20 weeks gestation to 7 years were assessed. Neurons in layers 3 and 5 were separately evaluated. The total dendritic length for all dendritic branches reached a maximum of 2800 microns for layer 3 neurons and 3400 microns for layer 5 neurons. At or before 40 weeks gestation, the dendritic tree of layer 3 neurons had reached 35% of the maximum compared with 55% of the maximum for layer 5 neurons. Dendritic branching occurred earlier in layer 5 and growth continued to be more advanced than in layer 3. After 40 weeks gestation in these layers no new branch orders were added to basal dendrites but 3 branch orders were added to apical dendrites. The determination of normal values for dendritic length, number of orders, and number of branches during early development provides a foundation for comparison of dendritic maturation in children with a variety of neurologic disorders.

Child↗

Effects of neurotransmitters and vagus nerve stimulation on diencephalic and mesencephalic neuronal activity.

The effects of microiontophoretically applied neurotransmitters and cervical vagus nerve stimulation on neuronal discharge frequency was determined for cells located in the lateral hypothalamus-lateral preoptic area (LH-LPA), medial hypothalamus, thalamus-zona incerta area, and midbrain of anesthetized rats. Seven barrel electrodes were utilized to record simultaneously from and apply gamma aminobutyric acid (GABA), dopamine, glutamate, acetylcholine and norepinephrine to single neurons. Microiontophoretically applied GABA resulted in similar decreases in neuronal discharge frequency in all central areas tested. Thalamus-zona incerta cells were the most sensitive to GABA and required the lowest ejection current for threshold responses. Dopamine application resulted in increases and decreases in hypothalamic and mesencephalic neuronal discharge frequency. Thalamus-zona incerta neurons were the most sensitive to dopamine and exhibited only decreased activity during its application. Glutamate application resulted in a non-specific excitation of neurons. Acetylcholine induced increases and decreases in neuronal discharge frequency. Thalamus-zona incerta cells were the most sensitive to acetylcholine application. Hypothalamic neurons were the most sensitive to norepinephrine induced decreases in neuronal activity and effects in this area persisted for a prolonged period after norepinephrine was applied. Neuronal discharge frequency was significantly increased during vagus nerve stimulation in all central areas studied. Only hypothalamic neurons also exhibited decreased activity during vagus nerve stimulation. Results are discussed in terms of previous neurochemical and neurophysiological data and in terms of the importance of vagal afferents in the control of central neuronal activity.

Animals↗

Spontaneous mesangiocapillary glomerulonephritis in Finn cross lambs from Alberta.

A spontaneous mesangiocapillary glomerulonephritis occurred in three, one to three month old Finnish Landrace cross lambs from a flock in northern Alberta. The ram was a purebred Finn sheep, and the ewes were Finn-Rambouillet and Finn-Suffolk-Rambouillet crosses. The lambs were found dead without previous clinical signs. Histologically there was marked thickening of glomerular capillary basement membranes, proliferation of mesangial cells, and peri-glomerular fibrosis. An interstitial infiltration of plasma cells and lymphocytes was present with occasional tubular degeneration and proteinaceous cast formation. Focal leukoencephalomalacia was present in one lamb. Electron microscopy demonstrated deposition of electron-dense deposits in a subendothelial location with occasional fusion of overlying foot processes in glomerular capillaries. Indirect immunofluorescence studies demonstrated positive staining material in glomerular capillary walls. These findings in Finnish Landrace cross lambs are characteristic of mesangiocapillary glomerulonephritis, a condition heretofore not reported in North America.

Animals↗

Muscle activity and the loss of electrical coupling between striated muscle cells in Xenopus embryos.

The gap junctions between embryonic striated muscle cells are lost during development. The time course of their elimination has been examined with electrophysiological techniques in myotomes of Xenopus laevis embryos. Gap junctions were detected by the passage of electronic current or the fluorescent dye, Lucifer Yellow, from one muscle cell to another. These tracers only spread to neighboring cells when injected intracellularly. All the muscle cells are electrically coupled at stage 24 when neuromuscular transmission begins, but normally many cells become uncoupled during the next 48 hr. In contrast, the muscle cells remain electrically coupled if neuromuscular transmission is blocked during that period with tricaine or alpha-bungarotoxin. When muscle activity recovers, the loss of coupling resumes. Once the coupling has disappeared, neuromuscular blockade does not restore it. Muscle contraction is blocked during development in a mutant of Xenopus, even though the muscle cells remain electrically excitable. After stage 32 in these immobile embryos, the muscle cells are stimulated repeatedly by regular bursts of neural activity. Although they never contract, the mutant muscle cells become uncoupled at the same time as the muscle cells in normal embryos. The results suggest that some consequence of repeated cholinergic activation, other than contraction, stimulates the loss of gap junctions between striated muscle cells during development. The elimination of gap junctions may be required for neural control of subsequent muscle differentiation.

Aminobenzoates↗

Myelination of the human vagus nerve from 24 weeks postconceptional age to adolescence.

Significant changes in respiratory reflexes occur with maturation. The vagus nerve, the pathway for the Hering-Breuer and irritant-receptor reflexes, was studied quantitatively in 33 infants and 5 adolescents. In the infants, total myelinated vagus fibers increased linearly (r m0.682, p less than 0.001) with postconceptional age (PCA), and by 40 weeks after conception, total counts were comparable to those of adolescent group. Counts of total myelinated vagus fibers in 16 term infants (greater than 41 weeks PCA) were comparable to those in the adolescent group (p less than 0.40), whereas 17 preterm infants (less than 38 weeks PCA) showed significantly fewer total myelinated vagus fibers than term or adolescent groups (p less than 0.001). Smaller-diameter (less than 2 micrometer) myelinated vagus fibers depended upon PCA in the preterm group (p less than 0.005), but were independent of PCA in the term group (p less than 0.5). Preterm infants have a higher percentage of small to total myelinated vagus fibers than term infants (p less than 0.1).

Adolescent↗

Abnormal neuronal development in the visual cortex of the human fetus and infant with down's syndrome. A quantitative and qualitative Golgi study.

The developmental morphology of visual cortical neurons (their numbers, dendritic arborization and numbers of spines) in 14 fetuses and infants with Down's syndrome were studied and compared with that of neurologically normal, age-matched controls. Fetuses with Trisomy 21 showed the same neuronal morphology and spine counts as control fetuses. However, the newborns and older infants with Down's syndrome showed shorter basilar dendrites and decreased numbers of spines with altered morphology and defective cortical layering.

Age Factors↗

Moderate, rapidly induced hypertension as a cause of intraventricular hemorrhage in the newborn beagle model.

Nine anesthetized, artificially ventilated, term newborn beagle puppies were given phenylephrine hydrochloride intravenously while systemic arterial, carotid arterial, and jugular venous blood pressures, and carotid arterial blood flow were monitored. Systemic blood pressure rose within seconds from a mean of 53.68 +/- 1.10 mm Hg to a mean of 81.92 +/- 5.14 mm Hg. Hypertension was maintained for up to one hour in each animal. Four of the nine pups had intraventricular hemorrhages that were visible to gross inspection at autopsy, and seven of the nine pups had subependymal hemorrhages. The blood pressures produced in these animals were within the range of those seen in premature infants. Thus, moderate, rapidly induced systemic hypertension may be a cause of intraventricular hemorrhage in the premature human newborn infant.

Animals↗