Biomedical subjects

S E DeRossett

Publications and source records attributed to S E DeRossett.

7 recordsLinked to original sources

PubMed1993

Thermal sensitivity in demyelinating neuropathy.

An 8-year-old girl with demyelinating peripheral neuropathy was observed to get markedly weak coincident with a febrile illness. With return of body temperature to normal over 24 hours, her strength improved back to baseline. Subsequently, we studied the effect of temperature on CMAP amplitude of two motor nerves in the patient and two control subjects. Both temperature, measured orally, was raised by immersing the subjects in hot water and lowered by passive cooling. With increase in temperature to 39.5 degrees C, the CMAP amplitudes were reduced by 80% in the patient's nerves compared to only 48% in the control nerves. These changes recovered with cooling to 36.9 degrees C. We conclude that demyelinated peripheral nerves are more susceptible to temperature-induced impulse blocking than healthy nerves and provide the first published evidence of the clinical consequences of this phenomenon in a demyelinating disease other than multiple sclerosis.

Action Potentials↗

PubMed1993

Novel brainstem syndrome associated with prostate carcinoma.

Two patients successfully treated for prostatic cancer developed a progressive neurologic syndrome beginning with loss of voluntary horizontal eye movements followed by severe, persistent muscle spasms of the face, jaw, and pharynx. Both had mild gait unsteadiness, and one exhibited facial and abdominal myoclonus. Extensive diagnostic studies, including MRIs of the brainstem (with and without contrast), were normal. CSF examination showed mild pleocytosis and elevated IgG. Quantitative eye movement recordings documented selective involvement of voluntary horizontal saccades with sparing of horizontal slow eye movements. Neither patient had antineuronal antibodies in the blood. Postmortem examination revealed perivascular chronic inflammatory cells and microglial infiltration of the pons and medulla. One patient also had perivascular infiltrates in both mesial temporal lobes. Neuronal loss was localized to the pontine tegmentum, the medullary sensory nuclei, and the cerebellum. Brainstem motor nuclei were preserved. The clinical and pathologic findings suggest an autoimmune process (probably paraneoplastic) with selective damage to a subpopulation of brainstem neurons critical for horizontal eye movements and recurrent inhibition of bulbar nuclei.

Adenocarcinoma↗

PubMed1986

Discriminative stimulus effects of the opioid antagonist diprenorphine in the squirrel monkey.

Squirrel monkeys were trained in a discrete-trial avoidance paradigm to discriminate i.m. injections of the opioid antagonist diprenorphine (0.1 mg/kg) from vehicle. When the monkeys could complete reliably at least 22 trials of a 25-trial session on the choice level appropriate for the substance injected before the session (i.e., diprenorphine or vehicle), tests of stimulus generalization to novel drug conditions were conducted. Mu receptor agonists (morphine, etorphine and buprenorphine) and kappa receptor agonists (ethylketocyclazocine, nalorphine and I-N-allylnormetazocine) produced dose-dependent diprenorphine-like discriminative effects. The dextrorotatory isomer of N-allynormetazocine was almost two-orders of magnitude less potent than the levorotatory isomer in this respect and phenycyclidine generalized to diprenorphine only partially, suggesting that the phencyclidine/sigma site does not have a prominent role in the discriminative effects of diprenorphine. Other nonopioid drugs (d-amphetamine, mescaline and pentobarbital) also did not produce discriminative effects comparable to those of the training drug. The pure opioid antagonists, naloxone, naltrexone, and WIN 44,441-3 [(2-alpha-6 alpha, 11S)-(-)-1-cyclopentyl-5-(1,2,3,4,5,6-hexahydro-8-hydroxy-3,6,11-trim eth yl-2, 6-metheno-3-benzazocin-11-yl)-3-pentanone] occasioned responding primarily on the lever appropriate for vehicle. Naloxone (1.0 mg/kg) blocked surmountably the diprenorphine-like discriminative effects of the mu and kappa agonists, displacing generalization curves to the the right by 10- to 100-fold; however, naloxone failed to shift the curve for diprenorphine itself. Thus, in the squirrel monkey diprenorphine has discriminative stimulus effects in common with mu- and kappa-opioid agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Effects of opiate antagonists and putative kappa agonists on unpunished and punished operant behavior in the rat.

The effects of naloxone and diprenorphine, opiate antagonists with different receptor-binding properties, and the putative kappa-receptor agonists, ketocyclazocine and ethylketocyclazocine (EKC), were studied on food-reinforced responding in rats. Behavior was maintained under a multiple-component 1-min variable-interval schedule in which 12-min periods of unpunished responding alternated with 4-min periods in which each response was punished by a brief electric footshock. Daily sessions were 1 h. Naloxone (0.01-10 mg/kg) decreased unpunished responding only slightly; punished responding was decreased significantly to 66% of control by 10 mg/kg. Diprenorphine (0.01-10 mg/kg) did not affect unpunished responding and increased punished responding dose-dependently to as much as 190% of control. EKC (0.01-1.0 mg/kg) decreased unpunished and punished responding dose-dependently and comparably, whereas ketocyclazocine (0.01-1.0 mg/kg) decreased unpunished responding but did not significantly affect punished responding. Diprenorphine was more potent than naloxone in blocking the decreases in responding produced by the kappa agonists. Differences in the behavioral effects of naloxone and diprenorphine appear to reflect the different receptor-binding properties of the two opiate antagonists.

Animals↗

PubMed1984

Effects of naloxone, diprenorphine, buprenorphine and etorphine on unpunished and punished food-reinforced responding in the squirrel monkey.

The effects of naloxone and three oripavine derivatives, diprenorphine, an antagonist, buprenorphine, a mixed agonist-antagonist, and etorphine, an agonist, were examined on food-reinforced responding in squirrel monkeys. Behavior was maintained under a multiple-component 1-min variable-interval schedule in which 12-min periods of unpunished responding alternated with 4-min periods in which each response produced a brief electric shock to the tail. Daily sessions were 1 hr. Responding in the two components was not differentially affected by any of the drugs. Naloxone decreased responding in both components only slightly at high doses (ED50 greater than 10 mg/kg). In contrast, the three oripavines produced prominent dose-related decreases in responding with the following order of potency for the nonpunishment component: etorphine (ED50 = 0.0005 mg/kg) greater than buprenorphine (ED50 = 0.02 mg/kg) greater than diprenorphine (ED50 = 0.11 mg/kg). Etorphine had a short duration of action (approximately 1 hr) whereas the actions of diprenorphine (1.0 mg/kg) and buprenorphine (0.1 mg/kg) persisted for 24 to 48 hr. Concurrent administration of naloxone (0.1 and 1.0 mg/kg) antagonized the response rate-decreasing effects of etorphine and buprenorphine in a dose-dependent manner (i.e., dose-response curves were shifted to the right) but failed to block the effects of diprenorphine. Although all three oripavines produced comparable decreases in food-reinforced responding, there are qualitative as well as quantitative differences between the drugs. Diprenorphine appears to act through a different mechanism from that of buprenorphine and etorphine.

Animals↗

PubMed1982

Effects of naloxone and diprenorphine on spontaneous activity in rats and mice.

The narcotic antagonist naloxone has been reported to decrease locomotor activity in the rat, presumably blocking endogenous opiate systems. Naloxone has a greater affinity for receptors which preferentially bind morphine and other opiate alkaloids as compared to receptors that bind endogenous opioid peptides. Diprenorphine, another pure opiate antagonist, binds with equal affinity to both receptor subtypes. Therefore, the effects of the narcotic antagonists naloxone and diprenorphine on spontaneous activity were compared in rats and mice, tested individually and in pairs. Only naloxone (10 mg/kg) affected spontaneous activity in rats tested individually, decreasing both gross and fine activity. In rats tested in pairs, naloxone (1.0 and 10 mg/kg) decreased both fine and gross activity, while diprenorphine (10 mg/kg) produced significant decreases only in fine activity. In mice tested individually, naloxone produced modest (nonsignificant) decreases in activity while diprenorphine (10 mg/kg) significantly enhanced activity. Neither opiate antagonist produced consistent effects on activity in paired mice. These results illustrate the species and situation dependence of the effects of opiate antagonists and point out the need for testing more than one narcotic antagonist in research designed to provide inferential information concerning possible physiological functions of endogenous opioid peptides.

Animals↗

PubMed1982

Enhanced analgesic response to morphine in adult rats exposed to morphine prenatally.

Morphine exposure during development has been shown to produce fetal tolerance to morphine as measured by spontaneous activity only if a particular injection schedule is used. The present study was undertaken to compare the morphine-induced analgesic response in adult offspring of rats which had been injected during the last half of gestation on schedules known to produce fetal tolerance (5 mg/kg morphine at 6 hour intervals) versus a schedule known not to produce fetal tolerance (10 mg/kg morphine at 12 hour intervals). At 30 days postnatally the offspring of animals injected on these 2 schedules show no changes in their responsiveness to the analgetic effect of morphine as determined in the hot-plate test. The present study shows that adult offspring of mothers injected with 20 mg/kg/day of morphine in four divided doses on days 12-20 of gestation have an enhanced analgetic response to morphine in the tail-flick test. In contrast, offspring of mothers injected during the same period of gestation with 20 mg/kg/day of morphine in two divided doses respond to the analgetic effect of morphine in the same manner as the offspring of saline-treated mothers. These results show that the schedule for prenatal morphine administration can play a role in the behavioral effects of morphine in adulthood.

Animals↗