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Biomedical subjects

A B Davidson

Publications and source records attributed to A B Davidson.

17 recordsLinked to original sources

Infection after total joint arthroplasty in patients with human immunodeficiency virus or intravenous drug use.

Patients with intravenous drug use (IVDU) and patients with human immunodeficiency virus (HIV) with painful joint arthrosis present a difficult treatment decision. The purpose of this study was to determine the rate of deep periprosthetic infection in patients with HIV or IVDU after total joint arthroplasty (TJA). Twenty-nine patients with HIV or a history of IVDU or both underwent TJA. Of 28 HIV-positive patients undergoing TJA, 4 (14%) developed infections. Two of 8 joints (25%) in the IVDU group developed an infection. Two of 5 joints (40%) with both IVDU and HIV developed a deep infection. Patients with HIV or a history of IVDU are more likely to develop a deep infection compared with other patients undergoing TJA. The decision to proceed with TJA in HIV-positive and IVDU patients should be made only after weighing the ratio of risks and benefits.

Adult↗

Emergency department management of occupational exposures: cost analysis of rapid HIV test.

OBJECTIVE: To compare costs for evaluation and treatment of a healthcare worker (HCW) experiencing an occupational exposure, using a rapid human immunodeficiency virus (HIV) test versus a standard enzyme-linked immunosorbent assay (ELISA) HIV test. DESIGN: Retrospective chart review of all HCWs presenting to the emergency department (ED) for care of an occupational exposure over a 13-month period. SETTING: A 404-bed university-based level 1 trauma center with an annual ED census of approximately 35,000. PARTICIPANTS: All HCWs experiencing an occupational exposure treated in the ED using a rapid HIV protocol were included in the analysis. METHODS: A calculation of selected costs of the initial evaluation and treatment of patients whose evaluation included a rapid HIV test on the source patient were performed. A similar calculation was then made for these patients, had the standard ELISA test been used. Evaluated costs included laboratory tests, postexposure prophylactic medications, and estimated lost work time. Other costs were constant and were not included in the evaluation. RESULTS: Total evaluated cost using the rapid HIV test as part of the evaluation and treatment protocol was $465.80 for 17 patients. Had the ELISA test been used instead of the rapid test, the total evaluated cost for the 17 patients would have been $5,965.81. CONCLUSIONS: When used as part of the evaluation and treatment of the HCW with an occupational exposure, the rapid HIV test results in substantial cost savings over the ELISA test .

AIDS Serodiagnosis↗

Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam.

The Observer's Assessment of Alertness/Sedation (OAA/S) Scale was developed to measure the level of alertness in subjects who are sedated. This scale was tested in 18 subjects in a three-period crossover study to assess its reliability and its criterion, behavioral, and construct validity. After receiving either placebo or a titrated dose of midazolam to produce light or heavy sedation, each subject was administered two sedation scales (OAA/S Scale and a Visual Analogue Scale) and two performances tests (Digit Symbol Substitution Test and Serial Sevens Subtraction). Two raters individually evaluated the subject's level of alertness on each of the two sedation scales. The results obtained on the OAA/S Scale were reliable and valid as measured by high correlations between the two raters and high correlations between the OAA/S Scale and two of the three standard tests used in this study. The OAA/S Scale was sensitive to the level of midazolam administered; all pairwise comparisons were significant (p less than 0.05) for all three treatment levels at both test periods.

Adult↗

Large-volume ventilation results in bronchoconstriction of Basenji-Greyhound dogs.

We compared the effects of large-volume ventilation on airway responses to aerosolized histamine in anesthetized mongrel dogs with its effects in Basenji-Greyhound crossbred (B-G) dogs. Before bronchoconstriction, large inflations resulted in only small changes of dynamic compliance (Cdyn) and pulmonary resistance (RL) in both groups of dogs. After the induction of a moderate degree of bronchoconstriction with aerosolized histamine, large inflations had a more substantial effect; Cdyn increased by 7.5 +/- 2.3% (mean +/- SE; P less than 0.05), and RL decreased by 32 +/- 3.4% (P less than 0.001) in the mongrel dogs. In the B-G group, Cdyn increased by only 0.2 +/- 1.8% (NS), and RL increased by 29.3 +/- 9.2% (P less than 0.05); these changes differed significantly (P less than 0.05) from those observed in the mongrel dogs. Large-volume ventilation following the administration of indomethacin (10 mg/kg iv) and histamine increased Cdyn by 11.4 +/- 1.8% (NS vs. without indomethacin) and decreased RL by 43.9 +/- 3.4% (P less than 0.05) in the mongrel group. In the B-G group large-volume ventilation increased Cdyn by 7.6 +/- 1.7% (P less than 0.01) and decreased RL by 15.7 +/- 8.1% (P less than 0.05). Thus indomethacin enhanced the bronchodilator effects of large-volume ventilation in mongrel dogs and reversed the bronchoconstrictor effect of this maneuver on RL in B-G dogs.

Animals↗

Bronchoconstrictor effects of leukotriene E4 in normal and asthmatic subjects.

The bronchoconstrictor activity of an aerosol of leukotriene E4(LTE4) was compared with that of histamine in 5 normal and in 6 asthmatic subjects to define the relative potency of LTE4 between the groups using 3 indices of airway response. The FEV1 and the flow rate measured at 30% of vital capacity from partial and maximal expiratory maneuvers (V30-P and V30-M) were measured. The geometric mean (GSEM) concentration of LTE4 required to reduce the V30-P by 30% was 0.30 (1.46) mM in the normal subjects, and 0.058 (1.63) in the asthmatic subjects; LTE4 was 39-fold more potent than histamine in the former and 14-fold in the latter group. Further, we observed that when normal and asthmatic subjects were compared at a degree of bronchoconstriction resulting in a 30% decrement in the V30-P after inhaling LTE4, there was a greater response in the asthmatic group than in the normal group of the accompanying change in the FEV1. The decrements in the FEV1 were not significantly different between the 2 groups after inhaling histamine. This study demonstrates that LTE4 is a potent bronchoconstrictor agonist in humans and suggests that airway responsiveness to this agonist differs substantially with the index of bronchoconstriction used for assessment of airway response.

Aerosols↗

Effect of tidal volume and anesthetic agent on airway responsiveness to histamine.

Dose-response relationships for bronchoconstriction in response to aerosal histamine were assessed before and after vagotomy in 11 dogs anesthetized with barbiturates and in 9 dogs anesthetized with alpha-chloralose-urethan. The dose-response relationships following vagotomy were assessed during spontaneous ventilation and during muscular paralysis and mechanical ventilation with tidal volume (VT) similar to each animal's VT prior to vagotomy. After vagotomy the spontaneous VT of both groups increased but the VT of the alpha-chloralose-urethan group was significantly less than that of the barbiturate group. The histamine responsiveness of the animals anesthetized with barbiturates was significantly greater during mechanical ventilation when VT was reduced to prevagotomy levels compared with during spontaneous ventilation. In contrast, the histamine responsiveness of the alpha-chloralose-urethan group was not significantly changed by reducing VT to prevagotomy levels. In six other dogs anesthetized with pentobarbital sodium and studied after vagotomy, responsiveness to histamine aerosol during controlled ventilation with breaths of prevagotomy VT was greater than responsiveness during mechanical ventilation with large volume breaths given immediately afterward. Thus the magnitude of VT of dogs after vagotomy may influence airway responsiveness, and the influence of anesthetic agents on airway responsiveness after vagotomy may in part be due to their effects on VT. Furthermore, bronchodilation accompanying large volume ventilation persists after vagotomy, suggesting that it is not exclusively mediated by changes in parasympathetic activity.

Airway Resistance↗

Pharmacological effects of Ro 22-1319: a new antipsychotic agent.

Ro 22-1319, a novel pyrroloisoquinoline compound, was identified as a potential antipsychotic agent in a rat discrete avoidance procedure that is highly specific for such agents. Results in this test are highly correlated with the clinical potency of all types of antipsychotic agents. The avoidance-blocking potency of Ro 22-1319 (0.7 mg/kg) in this procedure approached that of haloperidol (0.4 mg/kg) and was 7- and 12-times greater than that of chlorpromazine and clozapine, respectively. Ro 22-1319 exhibited similar high potency in other rat and monkey avoidance procedures, rat motor activity, and antagonism of apomorphine emesis in dogs. High potency and antipsychotic-like activity have been demonstrated in monkey EEG and in an in vivo 3H-spiroperidol binding assay. Although studies of amphetamine antagonism in rats indicate antidopaminergic activity at nigrostriatal sites, Ro 22-1319 exhibited relatively weaker cataleptogenic and antistereotypic activity than haloperidol, and had minimal activity in a rat chronic stereotypy model of receptor supersensitivity. This profile suggests that Ro 22-1319 is an efficacious antipsychotic compound, almost as potent as haloperidol, with fewer or less intense extrapyramidal effects and low potential for tardive dyskinesia.

Amphetamine↗

2-benzazepines. 5. Synthesis of pyrimido[5,4-d][2]benzazepines and their evaluation as anxiolytic agents.

A series of 5H-pyrimido[5,4-d][2]benzazepines has been synthesized, starting from the corresponding 2-benzazepin-5-ones, and evaluated as potential anxiolytic agents. Selected compounds from this series show a pharmacological profile of action different than that of diazepam. They are more potent than diazepam in the anti-pentylenetetrazole test and in the [3H]diazepam binding assay, yet show less activity in the inclined screen test. A pharmacological data profile is given for 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (7c). The structure-activity relationships of these potential anxiolytic agents are discussed.

Animals↗

Effects of chlorpromazine on continuous avoidance behavior in mice.

Previous reports have indicated that self-trained appetitive operant schedules of reinforcement can be acquired readily by mice using an apparatus which detects head movement responses. Using a similar apparatus, suitably modified, the utility of this methodology has been extended to an operant schedule of reinforcement in which behavior is maintained by an aversive shock stimulus. As previously demonstrated with various other CNS active drugs in the appetitive mouse procedures, the effects of chlorpromazine in the mouse continuous avoidance procedure described here were similar to those obtained in analogous standard rat procedures. These results increase the opportunities for experimenters to avail themselves of the advantages offered by the use of mice, rather than rats, in operant behavioral pharmacology.

Animals↗

A dopamine receptor model and its application in the design of a new class of rigid pyrrolo[2,3-g]isoquinoline antipsychotics.

A hypothetical model of the interaction of antipsychotic drugs with the dopamine receptor is described. This three-dimensional molecular model has been developed on the basis of plausible intermolecular interactions between pharmacophoric groups of diverse types of antipsychotic drugs and postulated amino acid side chain substituents of the receptor protein. Three essential binding sites (one possibly required for antagonism) and one lipophilic auxiliary binding site are identified. The geometry is defined via the three-dimensional structures of drugs exhibiting receptor activity, including (R)-apomorphine, (+)-dexclamol, and molindone (whose crystal structure has been determined). A new conformationally rigid pyrrolo[2,3-g]isoquinoline derivative has been designed to conform to the receptor model. The compound (+/-)-1 (2,6-dimethyl-3-ethyl-4,4a,5,6,7,8,8a,9-octahydro-4a,8a-trans-1H-pyrrolo[2,3-g] isoquinolin-4-one; Ro 22-1319) exhibits potent antipsychotic-like activity. The activity is stereospecific, residing in the (-) enantiomer, predicted and confirmed by X-ray crystal structure analysis of (-)-1.HCl to have the 4aR,8aR absolute configuration.

Animals↗

Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs.

The role of a transmembrane calcium influx in hypoxic pulmonary vasoconstriction was studied in isolated, blood-perfused, rat lungs. We reasoned that, if the influx of extracellular calcium mediated the hypoxic mechanism, pressor responses to alveolar hypoxia (2.5% O2) would be susceptible to inhibition by the calcium antagonists verapamil (2 X 10(-5) to 2 X 10(-1) mM) and SKF 525A (2.6 to 260 mM). Susceptibility of hypoxic pressor responses to inhibition by these calcium antagonists was contrasted to that of pressor responses elicited by the humoral vasoconstrictors angiotensin II(1 or 0.5 mug) and prostaglandin F2alpha (10 myg). Since neither saralasin (0.5 muM), a competitive antagonist of angiotensin II, nor meclofenamate (6.8 muM), an inhibitor of prostaglandin synthesis, depressed hypoxic pressor responses, it was concluded that these humoral transmitters were not directly involved in the hypoxic mechanism, and therefore served as independent reference agonists. The order of susceptibility of pulmonary pressor responses to inhibition by verapamil was hypoxia greater than angiotensin II greater than prostaglandin F2alpha. SKF 525A also reduced pressor responses to hypoxia more readily than those to angiotensin II. The greater inhibition of hypoxic pulmonary vasoconstriction by both calcium antagonists suggested that the hypoxic mechanism was critically dependent on the transmembrane influx of extracellular calcium. Mediation of the hypoxic response by this type of excitation-contraction coupling is consistent with the idea that hypoxia has a direct depolarizing effect on the vascular smooth muscle. It also provides a unifying explanation for inhibition of the hypoxic mechanism by various agents that have depressant or stabilizing actions on membranes in addition to other pharmacological effects.

Angiotensin II↗

A rapid automatic technique for generating operant key-press behavior in rats.

Experimentally naive rats were trained to key press on a fixed-ratio 10 schedule of food reinforcement by a completely automatic procedure within a single, 1-hr session. Control procedures demonstrated that the resulting behavior was an operant, under control of the schedule of reinforcement and the specified reinforcing stimulus (food). A simple, combination food-tray operandum, also described, was used as the basis for the training technique.

Journal Article↗