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R V Smith

Publications and source records attributed to R V Smith.

At least 73 records · Page 4Linked to original sources

Intradural disc rupture. Report of two cases.

Two cases of intradural disc rupture are presented, and 43 cases found in the literature are reviewed. Dandy's original observations concerning this lesion correlate well with contemporary experience. Characteristics of the history and physical findings are uniform enough to suggest a clinically identifiable syndrome. Microscopic examination of the Cytospin cerebrospinal fluid specimen and the use of computerized tomography with metrizamide may suggest the diagnosis preoperatively. Despite significant neurological deficit associated with lumbar lesions, the prognosis following surgery is good.

Aged↗

Stability of apomorphine in solutions containing ascorbic acid and bisulfite and effects of antioxidants on apomorphine-induced cage climbing and hypothermia in mice.

Ascorbic acid (100 mg/ml) and sodium bisulfite (0.5 and 20 mg/ml) prevented more than 10% oxidation of apomorphine hydrochloride in water maintained at room temperature over 1-3 days. Refrigeration at 5 degrees prevented oxidation of apomorphine hydrochloride in aqueous solutions for 1 week. Neither ascorbic acid nor sodium bisulfite affected murine stereotyped cage climbing or hypothermia induced by apaomorphine.

Animals↗

Synthesis of [8,9-2H2]apomorphine and [1,3,8,9-2H4]apomorphine for PMR, 13C-NMR, and mass spectral studies.

Methods are described for the preparation of [8,9-2H2]apomorphine and [1,3,8,9-2H4]apomorphine based on reaction of apomorphine in trifluoroacetic acid-d. The mass spectral properties of these compounds and of the O,O-bis(heptafluorobutyrate) ester and the O,O-bis(tert-butyldimethylsilyl) ethers of apomorphine, using electron impact and chemical ionization, are reported. [1,3,8,9-2H4]Apomorphine was used to elaborate the 13C-NMR chemical shifts of the proton-bearing carbons of apomorphine.

Apomorphine↗

Convenient synthesis of (S)-(+)-apomorphine from (R)-(-)-apomorphine.

A method was devised for preparing (S)-(+)-apomorphine from (R)-(-)-apomorphine. Dehydrogenation of the dimethyl ether of (R)-(-)-apomorphine with 10% palladium-on-carbon followed by reduction with sodium cyanoborohydride under acidic conditions resulted in quantitative racemization to give (R,S)-apomorphine dimethyl ether, which then was resolved with (-)-tartaric acid. Ether cleavage of (S)-(+)-apomorphine dimethyl ether (-)-tartrate with hydriodic acid in acetic anhydride yielded (S)-(+)-apomorphine, which was isolated as the hydrochloride salt in 99% enantiomeric excess.

Apomorphine↗

Hypothermic effects of N-n-propylnorapomorphine in mice: antagonism by neurotransmitter receptor blockers.

Six receptor blockers were compared in mice for their ability to alter hypothermia induced by the dopamine agonist N-n-propylnorapomorphine (NPA). The dopamine antagonist haloperidol inhibited NPA-induced hypothermia whereas phentolamine, propranolol, sotalol, atropine, cyproheptadine, or naloxone (alpha-adrenergic, beta-adrenergic, muscarinic cholinergic, serotonergic, and opiate antagonists, respectively) failed to inhibit it. The degree of antagonism of the hypothermic effect of NPA induced by haloperidol pretreatment suggests that the hypothermic response may serve as a useful model of specific dopaminergic activity of aporphines. Hypothermia induced by NPA and other aporphines may supplement the measure of aporphine-induced stereotypic cage-climbing previously reported to be specifically dopaminergic.

Animals↗

Behavioral facilitation following chronic administration of N-n-propylnorapomorphine.

Chronic administration of drugs which interfere with normal neurotransmission within animal nervous tissue (e.g. neurotransmitter receptor antagonists) is known to result in the development of behavioral supersensitivity. During recent years, evidence has been presented which indicates that neurotransmitter receptor agonists also produce behavioral supersensitivity. This study shows that, using stereotypic cage-climbing behavior in mice, chronic administration of apomorphine, and N-n-propylnorapomorphine (two direct-acting dopamine agonists) and d-amphetamine (an indirect dopamine agonist) produced an enhanced behavioral response to a test dose of apomorphine 4, 8 and 12 days after cessation of chronic drug injections.

Animals↗

Apomorphine-induced stereotypic cage climbing in mice as a model for studying changes in dopamine receptor sensitivity.

We have previously confirmed in mice that apomorphine (APO) induces dopamine specific stereotypic cage climbing. Apparent changes in dopamine receptor sensitivity induced by chronic drug administration appear to be measurable by this technique. In the present experiments, murine stereotypic cage climbing was evauated as a model system for assessing the dopamine receptor supersensitivity induced by chronic administration of the potent butyrophenone neuroleptic spiroperidol. Spiroperidol induced a significantly enhanced response induced by APO (about a 7-fold increase) manifest by 48 hr (but not 24 hr) following cessation of the last chronic injection. Time-response analyses demonstrated that the action of test doses of APO (1.0 or 4.5 mg/kg, IP) was significantly prolonged in the chronic-spiroperidol animals relative to controls. The supersensitivity in the spiroperidol-treated animals lasted more than three weeks for each dose of the neuroleptic and the APO dose-response curve was shifted to the left in spiroperidol-treated animals. Results are discussed in terms of the utility of the model for establishing dose-response, time-course, and duration of effect data within the same group of animals.

Animals↗

Stability of apomorphine in frozen plasma samples.

Apomorphine is relatively stable in plasma samples that are frozen for four weeks. Addition of 5mM ascorbic acid extends stability to at least ten weeks. The increased stability resulting from the antioxidant treatment may facilitate handling of plasma samples from clinical studies utilizing apomorphine.

Antioxidants↗

Stereotypic and hypothermic effects of apomorphine and N-n-propylnorapomorphine in mice.

Two dopaminergic agonists, apomorphine (APO) and N-n-propylnorapomorphine (NPA) were compared in mice for their ability to induce stereotypic cage-climbing and hypothermia. Stereotypic cage-climbing responses were recorded on videotape and subsequently rated "blind" in comparison to the animal's predrug behavior and to the behavior of animals administered control solutions. Hypothermia was measured as changes from predug body temperature. Both APO and NPA produced statistically significant cage-climbing and hypothermia vs. controls. Dose-response analyses (0.5-10 mg/kg, i.p.) indicated that on a milligram basis the two drugs induced similar magnitudes of stereotypic activity. In contrast, dose-response analyses (0.008-40 mg/kg, i.p.) of APO and NPA induced hypothermia suggested an approximate 90-fold greater effect for NPA. These results suggest that there may be two different types of dopaminergic systems responsible for the hypothermic and stereotypic responses measured.

Animals↗

Videotaping: the evaluation of stereotypic effects of antiparkinsonian agents.

Two experiments designed to assess the utility of a videotaping methodology in laboratory investigations of the stereotype effects of putative antiparkinsonian agents are presented. The technique minimizes experimental bias through the use of "blind" ratings and increases the rating accuracy through the use of within- and between-animals controls. Permanent videotape records allow training of raters to high efficiency, and direct comparisons of different rating scales under identical experimental conditions.

Animals↗