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Biomedical subjects

S Gleeson

Publications and source records attributed to S Gleeson.

At least 19 recordsLinked to original sources

Blockade of behavioral effects of bretazenil by flumazenil and ZK 93,426 in pigeons.

Benzodiazepine receptor partial agonists manifest full efficacy in preclinical tests of anxiolytic drug action but do not fully reproduce the discriminative stimulus effects of benzodiazepine receptor full agonists in pigeons. The partial agonist, bretazenil, binds to both diazepam-sensitive and diazepam-insensitive GABAA receptors. Previous studies have suggested a role for each of these receptor populations in some behavioral effects of bretazenil in pigeons. A possible role for these receptor subtypes in the behavioral effects of bretazenil was further investigated through drug interaction studies with the benzodiazepine receptor antagonists, flumazenil and ZK 93,426. Whereas flumazenil binds with high affinity to both receptor isoforms, ZK 93,426 binds preferentially to diazepam-sensitive binding sites. Bretazenil markedly increased punished responding of pigeons without significantly affecting nonpunished responding. In pigeons discriminating the full benzodiazepine receptor agonist, midazolam, from saline, bretazenil produced only 60-75% maximal effect. Flumazenil and ZK 93,426 neither increased punished responding nor substituted for midazolam, but dose-dependently blocked the effects of bretazenil on punished responding. Flumazenil also dose-dependently blocked the effects of bretazenil in midazolam-discriminating pigeons, whereas ZK 93,426 only attenuated this effect. These results indicate that bretazenil's actions as a partial agonist at diazepam-sensitive benzodiazepine receptors mediate increases in punished responding and substitution for the discriminative stimulus effects of midazolam in pigeons. The differences in the effects of flumazenil and ZK 93,426 on the discriminative stimulus effects of bretazenil suggest a potential contribution of diazepam-insensitive sites to this behavioral effect.

Animals

Relationship between behavioral and physiological indicators of pain, critical care patients' self-reports of pain, and opioid administration.

OBJECTIVES: To examine the accuracy of inferences about critical care patients' pain based on physiological and behavioral indicators and to assess the relationship between registered nurse and patient pain scores and doses of opioids administered. DESIGN: Descriptive, comparative analysis. SETTING: Three intensive care units and two postanesthesia care units in two hospitals. SUBJECTS: Fourteen critical care nurses who conducted 114 pain assessments on 31 surgical patients. INTERVENTIONS: Nurses used a pain assessment and intervention notation algorithm that contained lists of behavioral and physiological indicators of pain to make inferences about a patient's pain intensity. Fourteen registered nurses completed up to five pain assessments on each patient over a 4-hr period. Following both the physiological and behavioral ratings, nurses rated the patients' pain intensity, using a 0 to 10 numeric rating scale, and they asked patients to provide a self-report of pain intensity, using a similar numeric rating scale. Nurses then administered an intravenous dose of an opioid from a sliding scale prescription. MEASUREMENTS AND MAIN RESULTS: Moderate-to-strong correlations were found between the number of behavioral indicators at times 1 through 5 and between the number of physiological indicators and nurses' ratings of the patients' pain intensity at times 1 through 4 (p < .05). Although nurses' pain ratings were consistently lower than patients' pain ratings across the five time points, these differences were not significant. The amount of opioid analgesic administered by the nurse correlated more frequently with nurses' pain ratings than with patients' self-reports of pain intensity. CONCLUSIONS: The use of a detailed, standardized pain assessment and intervention notation algorithm that incorporates behavioral and physiological indicators may assist healthcare professionals in making relatively accurate assessments of a patient's pain intensity. Further research is needed to determine the specific decision-making processes and criteria that healthcare professionals use to choose doses of analgesics to administer to critically ill patients.

Adult

Behavioral and biochemical characterization of benzodiazepine receptor partial agonists in pigeons.

The ability of benzodiazepine receptor partial agonists to exhibit full efficacy in preclinical anxiolytic tests, in conjunction with initial clinical results, has suggested the possibility of a reduced clinical side-effect profile compared to benzodiazepine receptor full agonists like diazepam. Because punished behavior of pigeons has been useful in detecting effects of novel anxiolytic drugs, effects of imidazobenzodiazepine and beta-carboline benzodiazepine receptor partial agonists and some related compounds were evaluated in this species. The abilities of these compounds to substitute for the discriminative stimulus effects of the full agonists midazolam also was determined. Intrinsic efficacy was assessed by the degree to which gamma-aminobutyric acid increased ligand potency to displace [(3)H]Ro15-1788 (flumazinil) from membranes of pigeon cerebrum, and ranged from full agonist-like efficacy (Ro 19-5470; 7-(3-cyclopropyl-1,2,4-oxodiazol-5-yl)-5,6-dihydro-5-methyl-4H- imidazo[1,5a]-thieno[3,2-f]diazin-4-one) to minimal gamma-aminobutyric acid potentiations close to that of the antagonist flumazenil (abecarnil and Ro 41-7812; 7-chloro-4,5-dihydro-3-(3-hydroxy-1-propynyl)-5-methyl-6H-imidazo[1,5-a] -[1,4 ]benzodiazepine-6-one). Punished responding was increased markedly by midazolam and by all partial agonists, except Ro 41-7812 and Ro 42-8773 (7-chloro-3-[3-(cyclopropylmethoxy)-1-propynyl]-4,5-dihyro-5 -methyl-6H-imidaz o[1,5-a][1,4]benzodiazepine-6-one), at doses that did not affect nonpunished responding. In contrast to the full substitution generally observed in mammals, all of the partial agonists produced incomplete substitution (40-70%) in the midazolam drug discrimination procedure in pigeons. A positive relationship was observed between the degree of substitution and intrinsic efficacy. The benzodiazepine antagonists, flumazenil and ZK 93,426 (ethyl-5-isopropoxy-4-methoxymethyl-beta-carboline-3-carboxylate), neither increased punished responding nor substituted for midazolam. The results of the present study suggest that benzodiazepine receptor partial agonists and related compounds may provide full anxiolytic activity at doses that do not fully reproduce the subjective effect profile of full agonists.

Animals

Clinical judgment and management of postoperative pain in critical care patients.

BACKGROUND: Acute pain is a significant problem in critical care patients. Although many barriers to successful assessment and management of pain in critical care patients have been noted, little is known about how critical care nurses make clinical judgments when assessing and managing patients' pain. OBJECTIVE: This qualitative analysis is part of a pilot study evaluating nurses' use of a pain assessment and intervention notation algorithm in patients in critical care areas who have limited communication abilities after abdominal or thoracic surgery. METHOD: Transcribed audiotapes of nurse participants' "thinking aloud" while using the pain assessment and intervention notation algorithm were analyzed by using interpretive phenomenology. The interpretive account is based on 31 tape recordings of 14 nurses caring for 41 patients (12 patients in the ICU and 29 patients in the postanesthesia care unit). FINDINGS: The two domains of clinical judgment found were (1) assessing the patient and (2) balancing interventions. CONCLUSIONS: Many nurses' reports showed that they accurately assessed their patients' needs for analgesics. Through testing of and learning from their patients' responses, nurses were able to give amounts of analgesics that diminished patients' postoperative pain. Additionally, nurses had to balance analgesic administration against the patients' hemodynamic and respiratory conditions, medical plan and prescriptions, and the desires of the patients and the patients' families.

Adult

Effects of ibogaine on responding maintained by food, cocaine and heroin reinforcement in rats.

The effects of ibogaine (40 and 80 mg/kg, i.p.), an indole alkaloid proposed for the treatment of drug abuse, were determined in three different groups of rats responding under an FR10 schedule of food, cocaine or heroin reinforcement. Ibogaine (80 mg/kg, i.p.) given 60 min before the start of the session resulted in a 97% decrease in the number of ratios completed under the food reinforcement schedule and resulted in a decrease in responding the following day. Neither 40 mg/kg ibogaine given 60 min prior to the session nor 80 mg/kg given 24 h before the session suppressed responding maintained by cocaine infusions (0.33 mg/infusion). Pretreatment with 80 mg/kg ibogaine either 60 or 90 min prior to the session suppressed cocaine self-administration on the day it was administered and the longer pretreatment continued to suppress responding for 48 h. Responding maintained by heroin (18 micrograms/infusion) was the most sensitive to the effects of ibogaine. Both 40 and 80 mg/kg ibogaine resulted in an almost complete suppression of responding following a 60-min pretreatment period. Responding maintained by heroin returned to control levels the day following the administration of ibogaine.

Animals

Anxiolytic and antidepressant mechanisms of 5-HT1A drugs in the pigeon: contributions from behavioral studies.

The discovery that compounds acting through 5-hydroxytryptamine (5-HT) receptor subtypes can produce anxiolytic and/or antidepressant therapeutic effects in humans has resulted in considerable interest in the role of the 5-HT receptor system in both anxiety and depressive disorders. Because many of the clinically efficacious 5-HT1A anxiolytic drugs are either ineffective or produce inconsistent results in traditional or standard types of preclinical punishment or conflict procedures with rodents and other nonhuman mammals, there is considerable need for alternative behavioral assays sensitive to and selective for these compounds. In contrast to data with nonhuman mammals, 5-HT1A drugs are quite effective in pigeons studied under a punishment procedure. This paper reviews the use of the pigeon conflict procedure as a method for the detection and analysis of potential anxiolytic drugs acting through 5-HT1A receptors. Additionally, recent studies, also with the pigeon, have indicated that, in contrast to the rat, it is possible to establish an antidepressant such as imipramine as a discriminative stimulus, and then to use this procedure to evaluate the neuropharmacological bases for the behavioral and, presumably, therapeutic actions of these drugs. Using the drug discrimination procedure, it has been possible to examine a number of selective compounds that substitute for imipramine, thereby clarifying specific substrates for the antidepressant activity of this and related drugs. The pigeon promises to be a useful species in the pharmacological analyses of novel anxiolytic drugs and provides new approaches to the analysis and understanding of traditional as well as the more recently introduced antidepressant drugs.

Animals

The Good Heart, Good Life survey: self-reported cardiovascular disease risk factors, health knowledge and attitudes among Greek-Australians in Sydney.

This survey aimed to assess the prevalence and knowledge of coronary risk factors and self-perceived coronary heart disease risk among Greek-Australians in the Marrickville area of inner Sydney. A random sample of 834 household addresses was selected from the 2,403 households having Greek-Australian surnames on the electoral roll. In each household, one individual aged 18 years or over was selected using a Kish grid, and a questionnaire was administered by a bilingual interviewer. Questions concerned knowledge of and self-reported risk factors for coronary heart disease, and ratings of perceived stress, social support and networks. There was a response rate of 81 per cent of actual Greek-Australian households, a total of 541 interviews (61 per cent women). Most of the sample (86 per cent) were born in Greece and 77 per cent of interviews were administered in Greek. The age-adjusted male prevalences of self-reported smoking, high blood pressure, high blood cholesterol and body mass index over 26 kg/m2 were 44 per cent, 5 per cent, 14 per cent and 58 per cent, respectively. The age-adjusted female prevalences of self-reported smoking, high blood pressure, high blood cholesterol and body mass index over 26 kg/m2 were 19 per cent, 8 per cent, 15 per cent and 40 per cent, respectively. Compared to the National Heart Foundation risk-factor prevalence survey, the prevalence of self-reported high blood pressure was lower, but obesity and, among males, smoking, were higher. Low levels of education and poor English-language skills among older Greek-Australians may be contributing to the problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Neurochemical effects of 5-HT1 receptor ligands in pigeons.

Pigeon cerebrospinal fluid was assayed for 5-HT (5-hydroxytryptamine) and catecholamine metabolites after systemic drug injection. The 5-HT1-like receptor agonists 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole (RU 24969), 1-(m-trifluoromethylphenyl)piperazine (TFMPP), and 1-(3-chlorphenyl)piperazine (mCPP) decreased levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) without altering other metabolites. 5-HIAA decreases occurred at doses of 8-OH-DPAT and RU 24969 that have anti-conflict effects in pigeons, whereas TFMPP and mCPP decreased 5-HIAA only at behaviorally disruptive doses. The novel compound 1-(2-methoxyphenyl)-1-(4-(2-phthalimido)butyl)piperazine (NAN-190), a putative 5-HT1A receptor antagonist, did not affect 5-HIAA, but attenuated the decreases produced by the agonists. NAN-190 and the alpha 1-adrenoceptor antagonist prazosin increased levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol and had additive effects when co-administered. The rank order of potency in inhibiting [3H]8-OH-DPAT binding in pigeon cerebrum was 8-OH-DPAT = RU 24969 > NAN-190 >> mCPP > TFMPP. The results support suggestions that decreased 5-HT neurotransmission underlies the anxiolytic-like effects of 5-HT1A receptor agonists in pigeons.

8-Hydroxy-2-(di-n-propylamino)tetralin

Discriminative stimulus effects of 8-OH-DPAT in pigeons: antagonism studies with the putative 5-HT1A receptor antagonists BMY 7378 and NAN-190.

Pigeons were trained to discriminate 0.3 mg/kg of the 5-HT1A receptor agonist 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) from saline. RU 24969 (5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole), at doses of 5.6-10 mg/kg, and eltoprazine (5.6 mg/kg), both mixed 5-HT1A/B agonists, substituted completely for 8-OH-DPAT, whereas 3.0-10 mg/kg of the 5-HT1B/C agonist TFMPP (1-(m-trifluromethylphenyl)piperazine) and 0.1-3.0 of the 5-HT3 antagonist MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) yielded only saline-appropriate responses. Substitution for 8-OH-DPAT by eltoprazine and RU 24969, which does not occur in rats, provides in vivo support for the suggestion that the absence of a 5-HT1B receptor in the pigeon allows more complete expression of 5-HT1A-mediated effects. BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)]8-azaspirol-[4.5]- decane-7,9-dione) attenuated the 8-OH-DPAT stimulus at doses from 1.0 to 10 mg/kg but, when administered alone, also resulted in approximately 40% 8-OH-DPAT-appropriate responding at the highest dose. NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalamido)butyl)-piperazine (0.3-3.0 mg/kg) produced a dose-dependent and complete antagonism of the 8-OH-DPAT-discriminative stimulus; administered alone NAN-190 resulted only in saline-key responding. NAN-190 also reversed the rate-decreasing effects of higher doses of 8-OH-DPAT. The beta-adrenoceptor antagonist (+/-)-pindolol (5.6-17 mg/kg) antagonized the discriminative stimulus effects of lower 8-OH-DPAT doses but was unable to block the effects of higher doses of 8-OH-DPAT. Prazosin (1.0-10 mg/kg), which like NAN-190, is an alpha 1-antagonist, neither substituted for nor blocked the discriminative stimulus effects of 8-OH-DPAT. These results suggest that NAN-190 is an effective 5-HT1A receptor antagonist in this procedure with pigeons, with no indication of agonist actions, whereas BMY 7378 and pindolol are best characterized as partial 5-HT1A receptor agonists.

8-Hydroxy-2-(di-n-propylamino)tetralin

Reimbursement of biotherapy: present status, future directions--perspectives of the third-party payer.

The mission of insurers is to provide defined financial support for health care therapies deemed appropriate for use in specific clinical situations. In the current health care financial crisis, insurers are faced with keeping costs to a minimum and premiums reasonable. While insurers wish to finance the best available treatment, it is not always fiscally responsible or realistic to fund care provided in investigational therapies. The Blue Cross and Blue Shield Association (BCBSA), as the national coordinating body for local Blue Cross and Blue Shield Plans, assesses the status of new technologies, such as the biotherapy of cancer, through its Technology Evaluation and Coverage (TEC) Program and its Medical Necessity Program. Fundamental to both programs is whether a technology is effective: Does it improve health outcomes? And, if it does, what are its appropriate conditions of use? New technologies demonstrated by clinical research to improve health outcomes and found consistent with other related criteria are considered eligible for coverage by the TEC Program. New technologies not yet established as effective by clinical research and approved through the TEC Program are considered investigational. Most Blue Cross and Blue Shield Plan contracts exclude coverage for such investigational technologies. Most plan contracts also have medical necessity clauses, whereby only medically necessary technology uses are covered. Central to this is clinical research on appropriate medical conditions of use--the focus of the Medical Necessity Program. Valid conclusions on whether a technology works and where and when it works the best presuppose well-designed scientific studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Forecasting

The psychiatric technician: trespasser or welcomed ally?

1. The increasing shortage of nurses, higher patient acuity levels, and greater demands placed on nursing to meet standards of care have contributed to the use of psychiatric technicians to alleviate the burden on nursing and ensure the delivery of quality patient care. 2. Psychiatric technicians provide care for a select group of patients under the supervision of the primary nurse. The patients assigned to psychiatric technicians require minimal direct nursing intervention. 3. Psychiatric technicians reported increased self-confidence and self-esteem; the nurses were able to perform more professional nursing activities, increasing their job satisfaction and promoting staff retention; and the patients received high-quality care.

Hospitals, Urban

5-HT1A agonist effects on punished responding of squirrel monkeys.

Buspirone and other drugs that act as 5-HT1A agonists appear to be clinically effective anxiolytics in humans, yet their anticonflict effects, though robust in pigeons, are equivocal in rodents. In the present study we examined the effects of the benzodiazepine midazolam and a series of 5-HT1A agonists on punished responding of squirrel monkeys. Lever presses were reinforced according to a fixed-interval 3-min schedule; in addition, each thirtieth lever press was punished. Midazolam produced large increases in response rates, whereas none of the 5-HT1A compounds produced any increases in responding. Most of these drugs decreased response rates at the higher doses examined. Although the reasons for the discrepancy between species in the anticonflict effects of serotonergic anxiolytics cannot be specified, the different anatomical distribution of 5-HT1A binding sites across species may suggest a different functional role for this receptor.

Animals

Response acquisition with delayed reinforcement.

Discrete responses of experimentally naive, food-deprived White Carneaux pigeons (key pecks) or Sprague-Dawley rats (bar or omnidirectional lever presses) initiated unsignaled delay periods that terminated with food delivery. Each subject first was trained to eat from the food source, but no attempt was made to shape or to otherwise train the response. In both species, the response developed and was maintained. Control procedures excluded the simple passage of time, response elicitation or induction by food presentation, type of operandum, food delivery device location, and adventitious immediate reinforcement of responding as the basis for the effects. Results revealed that neither training nor immediate reinforcement is necessary to establish new behavior. The conditions that give rise to both the first and second response are discussed, and the results are related to other studies of the delay of reinforcement and to explanations of behavior based on contingency or correlation and contiguity.

Animals

Behavioral studies with anxiolytic drugs. VI. Effects on punished responding of drugs interacting with serotonin receptor subtypes.

The effects of drugs that bind selectively to different serotonin (5-HT) receptor subtypes were assessed in pigeons. Keypecking was maintained by a multiple fixed-ratio schedule of reinforcement in which responding also was punished during one component. The greatest increases in punished responding were produced by the buspirone analogs BMY 7378 and ipsapirone, which act at the 5-HT1A receptor. RU 24969, with high affinity for both 5-HT1A and 5-HT1B receptors, and 1-(2-methoxyphenyl)piperazine, a 5-HT1 compound, increased punished responding to a lesser extent, as did the 5-HT2 antagonists ketanserin and ritanserin. The 5-HT3 antagonists GR 38032F, ICS 205930 and MDL 72222 showed little systematic effect, and the mixed 5-HT1B/5-HT1C compound 1-(3-chlorophenyl)piperazine produced only decreases in punished responding. Levels of neurotransmitter metabolites in cerebrospinal fluid were assessed across a wide dose range of representative drugs used in the behavioral studies. Levels of the 5-HT metabolite 5-hydroxyindoleacetic acid were decreased significantly by BMY 7378 and ipsapirone, were not changed by ritanserin and were increased at one dose by MDL 72222. The results are consistent with suggestions that decreased 5-HT neurotransmission is involved in the effects of novel nonbenzodiazepine anxiolytics such as buspirone. Behavioral and neurochemical data also indicate that the effects of these drugs on other neurotransmitter systems do not play a significant role in their anxiolytic actions.

3,4-Dihydroxyphenylacetic Acid

Efficacy of ketoprofen in treating primary dysmenorrhea.

A 6-month double-blind crossover trial compared ketoprofen with placebo in the treatment of primary dysmenorrhea in 27 women who satisfied explicit inclusion and exclusion criteria. The response to treatment was assessed with a pain scale and a disability scale and by noting amelioration of associated symptoms, such as nausea, vomiting, diarrhea, fatigue, dizziness and headache. Ketoprofen was significantly superior to placebo in relieving the pain (p less than 0.001), disability (p less than 0.001) and headache (p less than 0.01) associated with menstruation. No order effect of treatment was observed. Adverse effects were few and minimal.

Adolescent