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Biomedical subjects

E R Young

Publications and source records attributed to E R Young.

At least 19 recordsLinked to original sources

Vinyl and alkynyl pyrimidines as michael acceptors: an approach to a cylindrospermopsin substructure.

Vinyl pyrimidine 9 and alkynyl pyrimidine 24 undergo base-mediated intramolecular conjugate addition reactions in which a carbamate and a urea, respectively, behave as nitrogen nucleophiles. The cyclic carbamate derived from 9 was converted to 11 via a metalation-oxidation reaction in which 2-phenylsulfonyl-3-phenyloxaziridine behaves as a hydroxylation reagent. The cyclic urea derived from 24 was converted to cylindrospermopsin substructure 30 using dimethyldioxirane to introduce the C(7) hydroxyl group.

Alkaloids↗

Genetic determinants of morphine activity and thermal responses in 15 inbred mouse strains.

Mice from 15 standard inbred strains were tested for sensitivity to two effects of acute morphine administration, open-field activity, and body temperature changes, at doses of 0, 4, 8, 16, and 32 mg/kg, I.P. Large strain differences were consistently observed, indicating a substantial degree of genetic determination of these traits. For morphine-induced activity, some strains were markedly insensitive to all doses (e.g., C3H/He, CE), while others showed increases and some decreases at the same morphine dose. For thermal responses, one strain was insensitive to all doses employed (C3H/He), while others showed marked hypothermia and some hyperthermia at the same dose. Although strains differed in brain morphine concentrations at time of behavioral testing, pharmacokinetic differences were unrelated to both measures of morphine sensitivity. Correlations among strain means (estimates of genetic correlations) were rather high across doses within each measure, indicating that strain differences to a given effect of morphine were rather stable across doses. This suggests substantial commonality in genetically mediated mechanisms across the dose range used for activity, and also for thermal responses. In contrast, genetic correlations between activity and thermal responses were not significant at any dose, indicating that these two traits are largely genetically independent.

Analgesics, Opioid↗

Maxillary nerve block: a case report and review of the intraoral technique.

Maxillary nerve blockade is not commonly used by general practitioners due to a lack of experience with the techniques involved and the fear of iatrogenic damage. Nevertheless, it represents an excellent method of producing profound anesthesia in the maxilla, with definite indications in selected instances. The anatomy and techniques associated with the maxillary block, as well as the indications, contraindications and complications are reviewed, and the use of the greater palatine foramen approach to treat a patient with a facial abscess is described.

Anesthesia, Dental↗

Effects of dizocilpine in withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice.

Mice selectively bred to be Withdrawal Seizure-Prone (WSP) or Seizure-Resistant (WSR) after chronic ethanol administration have been reported to be differentially sensitive to the anticonvulsant and proconvulsant effects on alcohol withdrawal of drugs interacting with glutamate receptors. Several behavioral effects of the noncompetitive glutamate receptor antagonist, dizocilpine, were determined in WSP and WSR mice to see whether their differential sensitivity generalized to effects unrelated to seizures, and to see whether it was only apparent during ethanol withdrawal. Dizocilpine potentiated the loss of righting reflex induced by ethanol, and dose-dependently stimulated habituated and nonhabituated open field activity. WSP and WSR mice were equally sensitive to these effects of dizocilpine. Pretreatment with dizocilpine increased the transcorneal amperage necessary to produce maximal electroshock seizures: WSR mice were more sensitive than WSP to this effect. Ethanol withdrawal (i.e., testing 6 h after a 24-h exposure to ethanol vapor) and dizocilpine had several effects on mice tested in the hole-in-wall apparatus. Several differences between WSP and WSR mice were also found, but in no case did dizocilpine differentially affect ethanol-withdrawing WSP and WSR mice. Across these experiments, differences between WSP and WSR mice in response to dizocilpine were rather specific. For some responses, WSP and WSR mice were equally sensitive, but only in the seizure-related measure assessed were naive WSR mice more sensitive than WSP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Voluntary consumption of ethanol in 15 inbred mouse strains.

To determine genetic differences in ethanol consumption, 15 commonly used inbred strains of mice were given ad libitum two-bottle choice between ethanol, 0.2% saccharin, or ethanol plus saccharin in one bottle versus tap water in the other bottle. Three different concentrations of ethanol were used: 3%, 6% and 10% (v/v). Of the 15 strains, the C57BL/6J, C57BR/cdJ and C57L/J strains showed the most consistent higher intake of ethanol either with or without 0.2% saccharin. In marked contrast, the DBA/1J and DBA/2J strains consistently showed the lowest intake. Consumption of 3% ethanol without saccharin was highly genetically correlated with saccharin consumption (r = 0.77), suggesting that low concentrations of ethanol may have a sweet taste that affects voluntary consumption. Most strains showed very different patterns of response to ethanol with or without saccharin. Three patterns of strain responses were identified. Some strains avoided higher concentrations of ethanol whether in water or saccharin; some appeared to be sensitive to the ability of saccharin to mask the odor of ethanol; and some may have reduced consumption only when ethanol concentrations were high enough to produce aversive postingestional effects. Whereas earlier studies generally attempted to explain strain differences in consumption by invoking a single mechanism, our results demonstrate that more than one mechanism is necessary to explain the preferential ethanol intake of all strains studied.

Alcohol Drinking↗

Serotonin and genetic differences in sensitivity and tolerance to ethanol hypothermia.

Mice have been selectively bred for genetic sensitivity (COLD) or insensitivity (HOT) to acute ethanol-induced hypothermia. COLD mice readily develop tolerance to the hypothermic effects of ethanol (EtOH) when it is chronically administered, while HOT mice do not. A number of studies have implicated serotonergic systems in both sensitivity and the development of tolerance to the hypothermic and ataxic effects of EtOH. In the experiments reported here, we administered the serotonin (5HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) to HOT and COLD mice before the acute and chronic administration of equipotent doses of EtOH. 5,7-DHT lesions significantly reduced (by about 65%) whole brain levels of 5HT in both selected lines. This treatment reduced sensitivity to acute EtOH hypothermia in COLD, but not in HOT mice, and blocked the development of tolerance only in COLD mice. Metabolites of 5HT, norepinephrine, and dopamine were generally increased in hypothalamic and brain stem tissue after acute EtOH injection, but HOT and COLD mice were not differentially susceptible to these effects. These results suggest that genes affecting 5HT systems may mediate some of the differences in response to the hypothermic effects of EtOH characterizing HOT and COLD mice.

5,7-Dihydroxytryptamine↗

Local anesthetic update.

The development of new local anesthetics has not been an area of particularly active research for a number of years. However, as the use of regional anesthesia has expanded, additional anesthetic requirements and techniques have stimulated the search for newer drugs and ways of modifying existing ones. This article reviews some of the more recent developments in this field.

Anesthesia, Dental↗

An anaphylactoid reaction following local anesthesia: a case report.

A case report of an adverse reaction to a preparation of an amide local anesthetic, prilocaine with epinephrine, is presented. Signs and symptoms were consistent with an anaphylactic reaction and the patient responded positively to treatment based on this assumption. Treatment included administration of epinephrine injected sublingually and oxygen by inhalation. However, subsequent skin testing failed to confirm this diagnosis. A number of explanations are possible and a final diagnosis of an anaphylactoid reaction was made. Local anesthetic allergies and their management are reviewed. The literature demonstrates that an allergic reaction to amide local anesthetics can occur and a thorough history, intradermal testing, and subcutaneous challenge are reasonable approaches to determine a safe agent for subsequent use.

Adult↗

Successful mandibular anesthesia following numerous unsuccessful attempts: a case report.

The management of a very anxious patient who had undergone uneventful dental treatment in the past, but posed a problem when clinicians attempted to secure profound mandibular anesthesia, is discussed. This case report also examines the advantages and disadvantages of the Gow-Gates mandibular block technique, and describes the patient's subsequent management.

Anesthesia, Dental↗

The pharmacology of local anesthetics--a review of the literature.

In the nineteenth century, some natives of Peru noticed circumoral numbness, euphoria and analgesia after chewing the leaves of the Erythroxylen coca bush. By 1850, cocaine was isolated from the plant, marking the start of the local anesthetic era in clinical medicine. Over the past 50 years, many synthetic local anesthetics have been developed which have fewer side effects, increased specificity of action and a wider margin of safety than cocaine. Currently, local anesthetics are used topically, for local infiltration; and intravenously, for peripheral nerve blockade, for sympathetic blockade, as well as for epidural and intrathecal use. Although the route of administration may affect pharmacokinetics and pharmacodynamics, it is the purpose of this article to review the general pharmacology of this entire range of clinically useful compounds.

Amides↗

Malignant hyperthermia and the general dentist: current recommendations.

Malignant hyperthermia is a potentially fatal disease that may be triggered by the administration of specific drugs or by stress. Although most often associated with general anesthesia, stress can be a significant stimulus and is therefore of concern to the general dentist. The decision as to how and where to treat these patients is complicated by conflicting recommendations from various sources. The aim of this article is to propose a protocol for the dentist to use in the treatment of patients with a history of malignant hyperthermia. The dentist must assess the patient for both their susceptibility to a crisis and the degree of stress of the planned procedure. For non-stressful treatment, it is reasonable to assume that the general dental practitioner can treat these patients in his office. For stressful treatment, advanced preparation is advised.

Anesthesia, Dental↗

Lack of differential effect by Ultracaine (articaine) and Citanest (prilocaine) in infiltration anaesthesia.

It has been claimed that anaesthesia of mandibular pulpal and lingual soft tissue, as well as maxillary palatal soft tissue, results following buccal infiltration of the local anaesthetic Ultracaine (articaine HC1). However, this has never been scientifically proven and the aim of this investigation was to test these claims by comparing articaine to a standard anaesthetic, Citanest (prilocaine HC1). In order to study this, a double blind, randomized trial was conducted in healthy adult volunteers. In these subjects, the ability to induce maxillary and mandibular anaesthesia following buccal infiltration with articaine (as compared to prilocaine given contralaterally), was determined by measuring sensation to electrical stimulation at the tooth, buccal and lingual soft tissue at each of the four non-carious, non-restored, second molars. Results showed that there were no statistically significant differences between articaine and prilocaine in their ability to induce anaesthesia for any tissue at any of the six sites (p greater than 0.05) as determined by chi-square analysis. Analysis of effect on sensation for 25 minutes post-administration also failed to demonstrate a difference between the two drugs. Therefore, these data are not consistent with superior anaesthesia efficacy by articaine at any site, including the mandibular pulpal, lingual or maxillary palatal tissues, in the second molars studied.

Administration, Buccal↗