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Biomedical subjects

L R Nelson

Publications and source records attributed to L R Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1987

Improved recovery from a traumatic-hypoxic brain injury in cats by intracisternal injection of an anion transport inhibitor.

Cats, injured by a mechanical plus hypoxic model of traumatic brain injury, were treated by intracisternal injection of a modified loop diuretic (L-644,711). This drug inhibits the chloride/bicarbonate anion exchange transport system. The treatment resulted in a significant decrease in mortality from 61 to 21%, and an improvement in both neurological status and EEG activity of the surviving animals. The dose of drug given intracisternally was at least 175 times less than the dosage we previously found was needed to achieve a comparable effect when the drug was given intravenously. The present results suggest that certain types of head injury can be treated by drugs which affect cellular anion transport processes in the brain.

Animals↗
PubMed1986

Morphine analgesia is potentiated in adult rats prenatally exposed to ethanol.

Exposure to inescapable, intermittent footshock elicits an opioid-mediated stress-induced analgesia in rats. We have previously shown that this response is markedly potentiated in adult rats, prenatally exposed to ethanol. To further investigate our hypothesis that endogenous opioid pain-inhibitory systems are modified by prenatal ethanol exposure, we have measured the analgesic response to morphine, in vitro brain opiate receptor binding characteristics, and occupation of brain opiate receptors following systemic administration of morphine. Compared to controls, rats prenatally exposed to ethanol had significantly enhanced morphine analgesia. This enhancement, however, does not appear attributable to changes in number or affinity of mu or delta opiate receptors, or to altered occupation of receptors by morphine.

Animals↗
PubMed1986

Pituitary-adrenal responses to morphine and footshock stress are enhanced following prenatal alcohol exposure.

The effect of prenatal ethanol exposure on pituitary-adrenal function in adult offspring was assessed by measuring corticosterone (CS) levels in plasma following exposure to two forms of footshock stress, intermittent and continuous, and after administration of 20 mg/kg of morphine. The footshock experiments were conducted at two time points in the circadian pituitary-adrenal cycle. Prenatally ethanol-exposed (E) rats had higher levels of CS than pair-fed and normal controls following intermittent footshock when tested at the crest of the CS circadian rhythm. However, this difference was not present when intermittent footshock was presented at the trough of the circadian cycle. At either time of day, there were no differences among the prenatal treatment groups in the basal condition or following continuous footshock. In addition, E rats had significantly higher levels of plasma CS than controls following morphine. Plasma adrenocorticotropin (ACTH) levels were measured after intermittent footshock at the crest of the circadian rhythm and were significantly higher in E rats than in controls. These results extend our previous reports of enhanced activation of the hypothalamo-pituitary-adrenal axis in response to other stressors as well as to ethanol in adult rats exposed to ethanol in utero. They also confirm that E rats are differentially hyperresponsive only to intermittent footshock stress, not to continuous footshock, as we had found to be the case when the analgesia induced by these two stressors was the dependent measure.

Adrenocorticotropic Hormone↗
PubMed1985

Banding of rubro-olivary terminations in the principal inferior olivary nucleus of the chimpanzee.

An electrolytic lesion centered just dorsal to, and grazing the superior surface of, the rostral red nucleus (RNr) was produced stereotactically in a single chimpanzee. Perikarya of the ipsilateral RNr exhibited retrograde cell changes, demonstrating interruption of its efferent fibers. The degenerated rubro-olivary tract was followed in silver impregnated material to the ipsilateral compact part of the pedunculopontine nucleus, pontine reticular formation and inferior olivary complex. Within the inferior olivary complex, terminations were banded and restricted to the principal subnucleus.

Animals↗
PubMed1985

Opioid but not nonopioid stress-induced analgesia is enhanced following prenatal exposure to ethanol.

Two neurochemically distinct forms of stress-induced analgesia were examined in adult rats following prenatal ethanol exposure. Rats were exposed to ethanol during the last 2 weeks of gestation through a liquid diet presented to the dams. Analgesia testing was conducted when the offspring were 150-210 days of age. Two forms of footshock stress were administered; one that resulted in a naloxone-sensitive (opioid-mediated) analgesia and one that resulted in a naloxone-insensitive (nonopioid) form of analgesia. Rats prenatally exposed to ethanol demonstrated significantly enhanced opioid-mediated analgesia, but unaltered nonopioid analgesia compared to controls. These results confirm previous findings that prenatal exposure to ethanol leads to long-term alterations in responding to some, but not all forms of stress. The possibility that prenatal exposure to ethanol leads to perturbations in the endogenous opioid systems is discussed.

Analgesia↗
PubMed1985

Medical management of congenital nasolacrimal duct obstruction.

One hundred thirteen consecutive children seen with congenital nasolacrimal duct obstruction were treated with local massage and topical antibiotic ointment. The obstruction was resolved in 107 patients within eight months of initiation of this form of management. Nearly all of the children were spared a surgical procedure that probably would have been performed if early probing of the nasolacrimal system had been advocated.

Erythromycin↗
PubMed1984

Altered stress responsiveness in adult rats exposed to ethanol in utero: neuroendocrine mechanisms.

In our first studies the activity of the hypothalamo-pituitary-adrenal (HPA) axis was found to be significantly greater in response to certain stressors, including ethanol, in adult rats exposed to ethanol as fetuses (fetal ethanol-exposed [FEE] rats) than in pair-fed-derived or normal controls. Stress responsiveness in FEE rats was examined further by measuring stress-induced analgesia after inescapable footshock. Analgesia was enhanced in adult FEE rats by a prolonged/intermittent naloxone-reversible form of footshock, but not by a brief/continuous naloxone-insensitive form, suggesting that the effect was opioid-mediated. Adult FEE rats showed greater analgesic and plasma corticosterone responses to morphine challenges than control rats. Preliminary results also indicated that when adult FEE rats were exposed daily to the intermittent footshock stress (10 min/day) they consumed significantly more ethanol than controls. Whether the altered stress responsiveness reflects fetal ethanol-induced effects on the development of the HPA axis was determined by measuring brain and plasma content of corticosterone in FEE and control neonates. At birth, in FEE pups, whole brain and plasma corticosterone levels are significantly raised. On postnatal day 7, when basal plasma corticosterone concentrations have attained normal values, FEE rats display blunted corticosterone responses to ethanol administration, indicating persistent effects of the fetal ethanol exposure despite its termination one week previously. The precise contribution of these neonatal hormonal alterations to the long-term effects of fetal ethanol exposure on stress responsiveness remains to be determined.

Alcohol Drinking↗
PubMed1983

Increased consumption of diazepam during continuous amphetamine administration.

Previous investigations in our laboratory have demonstrated that after implantation of slow-release d-amphetamine pellets, rats with free access to water and a 10% ethanol solution selectively increase their consumption of the ethanol solution. We now report that this d-amphetamine treatment produces a similar increase in drinking of a benzodiazepine (diazepam) solution. Female albino rats were given free access to water and a 0.060 mg/ml diazepam solution and fluid intake was recorded every two days. The baseline consumption of diazepam averaged 25% of the total daily fluid intake. After d-amphetamine pellet implantation, rats increased their diazepam consumption to an average of 48% of total fluid intake, whereas rats implanted with control pellets containing vehicle only showed no change in diazepam drinking.

Animals↗
PubMed1982

The effects of division rate-limiting amounts of fetal bovine serum on the proliferation and aging of cultured chick cells.

Chick embryo fibroblasts serially propagated in media containing division rate-limiting amounts of fetal bovine serum underwent premature culture senescence as illustrated by accelerated declines in the number of cells incorporating 3H-thymidine, increased population doubling times, reduced cell densities at subcultivation, and reduced replicative life-spans compared to cells grown in medium containing non-rate-limiting amounts of serum. Low serum serially propagated "senescent" cultures returned to 10% serum containing medium had proliferative rates, incorporated 3H-thymidine, and attained saturation densities at confluency similar to younger cells. "Senescent" cells serially propagated in low serum and returned to 10% serum, achieved life-spans similar to cells continuously grown in the presence of 10% serum. The results of these and other studies show that cells serially propagated in the presence of division rate-limiting amounts of fetal bovine serum, or at high inoculation densities, accumulate a substantial number of cells in the population during exponential growth conditions that are not senescent but are prevented from entering DNA synthesis because of mitogen limitations. Our results indicate that the amount of serum mitogen in the growth medium affects only the rate at which cells express their genetically predetermined replicative potential and not the replicative life-span per se. These results are discussed in relation to the techniques that should be employed for studying cellular aging and the mechanism of senescent cell formation.

Aging↗
PubMed1982

Agents for the treatment of brain injury. 1. (Aryloxy)alkanoic acids.

Blunt and ischemic injuries of the brain have been shown to result in swelling that is predominantly limited to a single cell type, the astrocyte, within the complex cellular mosiac of cerebral gray matter. Evaluation of various diuretic (aryloxy)acetic acids in vitro using incubating cat brain slices and primary astrocyte cultures identified compounds with marked ability to inhibit brain tissue swelling. Some of the compounds significantly reduced the mortality and morbidity following acceleration/deceleration brain injury in anesthesized cats. A variety of (indanyloxy)alkanoic acids were synthesized which were analogous to the dually active (indanyloxy)acetic acids. Some of the 4-(indanyloxy)butanoic acids were found to be devoid of diuretic activity but to possess equal or greater activity than the dually active compounds in the in vitro and in vivo brain assays. Selected examples from both the (indanyloxy)acetic and 4-(indanyloxy)butanoic acid series showed marked chiral effects, with one enantiomer generally exhibiting a much greater activity than the other. A clinical study of severely head-injured patients treated with ethacrynic acid demonstrated a significantly improved outcome when compared to controls. These data suggest a clinical advantage for the nondiuretic (aryloxy)alkanoic acids which possess in vitro and in vivo activities in the cat brain assays that are comparable or superior to dually active compounds.

Animals↗
PubMed1982

Frontal sinus ablation for frontal osteomyelitis.

Frontal sinusitis with frontal osteomyelitis is a potentially life threatening disease. Diagnostic and therapeutic errors occur frequently because of antibiotic masking of already silent frontal lobe complications or lack of suspicion on the part of the otolaryngologist or the neurosurgeon. Frontal sinus infection and/or trauma frequently require otoneuro cooperation for care. Four cases of complications of frontal sinus infection with osteomyelitis are discussed. Three had epidural empyemas and one had a subdural empyema with an anterior 1/3 superior sagittal sinus thrombosis and multiple brain abscesses. Each patient was approached through a frontal craniotomy and the frontal sinus posterior plate examined from behind. Each had posterior dehiscences. Follow-up of osteomyelitis requires multiple tests including computerized tomography, polytomography and possibly bone or gallium scans. Twenty year or more follow-up is essential.

Adolescent↗
PubMed1981

Adenosine-stimulated astroglial swelling in cat cerebral cortex in vivo with total inhibition by a non-diuretic acylaryloxyacid derivative.

The intact cerebral cortices of cats were exposed in vivo under normothermic conditions and superfused with isotonic artificial cerebrospinal fluid containing added 0.125 mM adenosine. This resulted in chloridecation-rich cerebrocortical swelling which was shown by electron microscopy to be associated with an expanded astroglial compartment. The addition of DCPIB, a non-diuretic acylaryloxyacid analogue of ethacrynic acid and an inhibitor of coupled chloride-cation transport in cerebral cortex in vitro, totally blocked astroglial swelling and the concomitant increases in tissue ion contents. These studies support our previous experiments on the mechanism of formation of astroglial swelling. The pathological consequences of astroglial swelling and the clinical applications of these findings are discussed.

Adenosine↗
PubMed1980

Biology of glial swelling in experimental brain edema.

Most studies of clinically relevant cerebral edema emphasize the effect of added tissue fluid in white matter on gross distortion with transtentorial and subfalcine brain herniation. Our recent studies on altered tissue fluid compartmentation in cerebral gray matter suggest that significant microdistortion of relationships of capillaries to subserved tissue follows swelling of astroglia therein. Grave consequences to solute and gas exchange in focal regions may well be expected and are emphasized. The elucidation of the mechanisms of formation and inhibition of astroglial swelling by chemical agents, including chemically useful acylaryloxyacetic acid derivatives, are discussed. Furthermore, the effect of these agents in altering mortality and morbidity in a controlled, random study of animal head injury is presented.

Animals↗
PubMed1979

Analysis and measurement of some sources of variability in experimental spinal cord trauma.

Experiments were performed on anesthetized cats to determine whether the variability that is common in experimental spinal cord injuries produced by the weight-drop technique can be reduced if a more accurate determination of the actual intensity of the insult to the cord is measured. In addition, determinations of the contribution of such variables as mass of drop-weight, impounder diameter, and animal weight to variability were made. It was found that of the three measures of intensity readily available from a strain gauge transducer, impulse (change in momentum of drop-weight) showed the highest correlation with the histologically determined extent of the lesion. It was shown that the mass of the drop-weight had a significant effect on lesion size even when the gram X centimeter quantification of the injury was constant. Animal weight and impounder diameter did not make a significant contribution to the variability of injury as determined by low-power microscopy.

Acceleration↗