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Biomedical subjects

R A Wise

Publications and source records attributed to R A Wise.

At least 19 recordsLinked to original sources
PubMed1992

Acute depolarization block of A10 dopamine neurons: interactions of morphine with dopamine antagonists.

Extracellular single-unit recording techniques were used to determine the effects of morphine, administered either systematically (intravenous) or locally (microiontophoresis), on ventral tegmental area (A10) dopamine (DA) neuronal activity in animals pretreated with D1 (SCH 23390) or D2 (pimozide) DA receptor antagonists. In rats pretreated with the D2 antagonist pimozide, A10 DA neurons readily entered a state of apparent depolarization block in response to either i.v. or iontophoretically applied morphine. Whether the inactivation of DA neurons was induced by systemic or local morphine, it was reversed in 22 of 27 cases by iontophoretic administration of the inhibitory amino acid transmitter gamma-aminobutyric acid (GABA), suggesting depolarization block as the underlying mechanism. Pretreatment of rats with the D1 antagonist SCH 23390 did not significantly alter the tendency of A10 DA neurons to enter apparent depolarization block in response to morphine. These data support recent behavioral evidence suggesting that the combination of systemic pimozide and ventral tegmental area morphine can result in depolarization inactivation of the mesoaccumbens DA reward system.

Analysis of Variance↗
PubMed1992

Anticentromere antibody as a predictor of digital ischemic loss in patients with systemic sclerosis.

OBJECTIVE: To determine the clinical and serologic risk factors for digital ischemic events in patients with systemic sclerosis (SSc). METHODS: Retrospective review of clinical and laboratory data and review of current clinical status of 98 patients with SSc, seen between 1985 and 1990. RESULTS: Amputation of 1 or more digits due to ischemia occurred in 20.4% of the patients; 9.2% had multiple digit loss. Sclerodactyly alone and anticentromere antibody (ACA) were associated with loss of 1 or more digits. Age, smoking status, duration of disease, or duration of Raynaud's phenomenon were not predictive for loss of digits. CONCLUSION: Patients with limited SSc who are positive for ACA have an increased risk of major peripheral vascular occlusive disease.

Adult↗
PubMed1992

Localization of drug reward mechanisms by intracranial injections.

Intracranial drug injections are useful in localizing brain areas where drugs of abuse initiate their habit-forming actions. However, serious methodological problems accompany such studies. Pharmacological controls are necessary to assess non-receptor-mediated local actions of the drug, anatomical controls are necessary to rule out drug efflux to distal sites of action, and behavioral controls are necessary to separate rewarding from general activating effects of drugs. Five brain sites have been advanced as sites of rewarding opiate actions: the ventral tegmental area (VTA), nucleus accumbens septi (NAS), lateral hypothalamus, periaqueductal gray, and hippocampus. Current evidence appears to confirm two of these--VTA and NAS; evidence is currently incomplete in the case of the hippocampus and is conflicting in the case of the lateral hypothalamus and periaqueductal gray. Two sites have been advanced as sites of rewarding psychomotor stimulant actions: NAS and the frontal cortex; each site seems implicated, but puzzling differences between amphetamine and cocaine findings remain to be resolved. Each of the clearly implicated sites is local to dopamine cell bodies or dopamine terminals that have been implicated in the rewarding effects of brain stimulation, food, and sex.

Animals↗
PubMed1992

Locomotor-activating effects of the D2 agonist bromocriptine show environment-specific sensitization following repeated injections.

Biphasic effects of bromocriptine (2.0, 5.0, 10.0, and 20.0 mg/kg IP) on locomotion were quantified in photocell activity boxes in rats. Following early suppression of activity, bromocriptine produced a clear, dose-dependent increase in locomotion that lasted several hours. When a low dose of bromocriptine (5.0 mg/kg) was administered daily over a 3-week period, the locomotor-activating effects of the drug showed progressive enhancement over days. The sensitization was environment specific; rats administered bromocriptine six times in the home cage showed no sign of a sensitized response to bromocriptine when subsequently tested in the activity box. Thus, selective stimulation of D2 receptors stimulates locomotion and sensitizes animals to subsequent injections, just as do the indirect-acting dopamine agonists cocaine and amphetamine.

Animals↗
PubMed1992

Reinstatement of heroin self-administration habits: morphine prompts and naltrexone discourages renewed responding after extinction.

The effects of morphine, naltrexone, and nalorphine were studied in rats trained to lever-press for intravenous heroin and then tested under conditions of non-reinforcement. Animals were reinforced for lever-pressing on a continuous reinforcement schedule (100 micrograms/kg per infusion) for 2-3 h each day following which reinforcement was terminated and animals were studied under extinction conditions for the remainder of the session. Each day following the termination of responding under extinction conditions, animals were given a single injection of saline, morphine, nalorphine, or naltrexone; lever-pressing under the extinction conditions was then observed for several hours. When animals adapted to this regimen, very low levels of responding were seen following saline injections; morphine (2 or 10 mg/kg) reinstated vigorous responding that lasted 1-4 h. Naltrexone (2 mg/kg) suppressed responding below the levels seen after saline, and nalorphine (10 mg/kg) had the same effect as saline. These observations support the view that opioid-seeking behavior is primed by the proponent or opioid-like actions of opioids and not by the opponent or drug-opposite effects associated with opioid withdrawal.

Animals↗
PubMed1992

Feature-based detection of the K-complex wave in the human electroencephalogram using neural networks.

The main difficulties in reliable automated detection of the K-complex wave in EEG are its close similarity to other waves and the lack of specific characterization criteria. We present a feature-based detection approach using neural networks that provides good agreement with visual K-complex recognition: a sensitivity of 90% is obtained with about 8% false positives. The respective contribution of the features and that of the neural network is demonstrated by comparing the results to those obtained with i) raw EEG data presented to neural networks, and ii) features presented to Fisher's linear discriminant.

Electroencephalography↗
PubMed1992

Effects of systolic and diastolic positive pleural pressure pulses with altered cardiac contractility.

Positive pleural pressure (Ppl) decreases left ventricular afterload and preload. The resulting change in cardiac output (CO) in response to these altered loading conditions varies with the baseline level of cardiac contractility. In an isolated canine heart-lung preparation, we studied the effects of positive Ppl applied phasically during systole or diastole on CO and on the cardiac function curve (the relationship between CO and left atrial transmural pressure). When baseline cardiac contractility was enhanced by epinephrine infusion, systolic and diastolic positive Ppl decreased CO equally (1,931 +/- 131 to 1,419 +/- 124 and 1,970 +/- 139 to 1,468 +/- 139 ml/min, P less than 0.01) and decreased the pressure gradient driving venous return. However, neither shifted the position of the cardiac function curve, suggesting that the predominant effect of positive Ppl was decreased preload. When baseline cardiac contractility was depressed by severe respiratory acidosis, diastolic positive Ppl pulses caused no significant change in CO (418 +/- 66 to 386 +/- 52 ml/min), the cardiac function curve, or the pressure gradient for venous return. However, systolic positive Ppl pulses increased CO from 415 +/- 70 to 483 +/- 65 ml/min (P less than 0.01) and significantly shifted the cardiac function curve to the left. Thus the effect of Ppl pulsations on CO works through different mechanisms, depending on the state of cardiac contractility.

Animals↗
PubMed1992

Effects of positive end-expiratory pressure on the canine venous return curve.

To study the mechanism whereby positive end-expiratory pressure (PEEP) decreases venous return, we used a closed-chest canine venous bypass preparation to study the effects of 10 mm Hg PEEP on the systemic venous pressure-flow curves from the superior and inferior vena cava (SVC and IVC). These curves were characterized by three variables: the critical downstream pressure below which venous return was maximal (PCRIT), the conductance to venous return (GVR), and the effective upstream pressure driving venous return. PEEP reduced venous return by decreasing the maximal venous return even when the pressures at the outflow of the IVC and SVC were maintained below zero. PEEP increased PCRIT in the SVC and IVC (SVC: -0.31 +/- 0.53 to 3.21 +/- 0.84; IVC: -0.41 +/- 0.64 to 5.23 +/- 1.02 (SE) mm Hg; p less than 0.005). GVR in the SVC was reduced (52.5 +/- 26 to 37.8 +/- 5.3 (SE) ml/min/mm Hg; p less than 0.005), but changes in the IVC did not reach statistical significance. These changes were partially offset by increases in the upstream pressure driving venous return (SVC: 9.44 +/- 0.54 to 12.25 +/- 0.71; IVC: 9.42 +/- 0.69 to 12.51 +/- 1.02 (SE) mm Hg; p less than 0.01). Analysis of these findings suggests that PEEP may alter venous return through effects on the peripheral circulation, independent of its effects on the heart.

Animals↗
PubMed1992

Metered-dose inhaler adherence in a clinical trial.

We studied patterns of inhaler usage in a sample of participants from two centers in the Lung Health Study clinical trial. The inhaler, containing either ipratropium bromide or a placebo, was prescribed to be taken as two inhalations three times daily. For 4 months we recorded adherence by both self-report (n = 95) and canister weight change (n = 70). We compared these results with data obtained from a microprocessor monitoring device, the Nebulizer Chronolog (NC), which records the date and time of each inhaler actuation. Seventy-three percent of the participants reported using the inhaler an average of three times daily; however, NC data showed that only 15% of the participants actually used the inhaler an average of 2.5 or more times per day. Canister weight overestimated adherence because only 62% of the NC sets contained the prescribed two actuations. Fourteen percent showed a pattern of actuation of their inhalers more than 100 times in a 3-h interval. We interpret this usage pattern to reflect deliberate emptying of inhalers to appear to be in good compliance with the prescribed program. We conclude that self-report and weighing of inhaler canisters overestimate adherence to the prescribed regimens. Furthermore, a substantial number of monitored inhaler users appear to deliberately dump their medication prior to follow-up visits.

Administration, Inhalation↗
PubMed1992

Increase in translaryngeal resistance during phonation in rheumatoid arthritis.

Laryngeal involvement by RA is a common finding, but there have been no studies of laryngeal function in RA patients. This study was undertaken to determine if patients with rheumatoid arthritis have functional abnormalities of the upper airway during phonation which may be the result of synovitis of the laryngeal joints caused by RA. Translaryngeal resistance was measured in six patients with RA and six matched control subjects using an interrupter method to measure PSG and V during vocalization. Patients with RA had a higher R (65.0 +/- 8.15 cm H2O/L/s) than control subjects (38.4 +/- 7.43 cm H2O/L/s [p less than 0.05]). This was the consequence of lower V rates during phonation at similar PSG. We conclude that abnormalities of the larynx in RA patients are common and cause measurable physiologic abnormalities.

Adult↗
PubMed1992

Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis.

OBJECTIVE: We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud's phenomenon secondary to systemic sclerosis. METHODS: Thirty-five patients with Raynaud's phenomenon secondary to systemic sclerosis, including 11 with digital ischemic ulcerations, were enrolled in a double blind placebo controlled parallel study in 2 centers. Following a 2 week washout, subjects received intravenous iloprost (0.5-2.0 ng/kg/min) or saline by continuous infusion for 6 h on 5 consecutive days. Clinical assessments, status of digital ulcers, measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge, were performed at entry, at 5 days of therapy and at biweekly intervals for 10 weeks. RESULTS: Complete healing of all cutaneous lesions (ulcers, fissures, and paronychia) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo (p = 0.015). Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group, but none in the placebo group (p = 0.029). Patient diaries of frequency, duration and symptoms of Raynaud's phenomenon showed improvement in both groups. Critical ischemic temperature (finger temperature during controlled cold challenge at which Raynaud's or loss of detectable digital blood flow occurred) progressively decreased in the iloprost group from 21.3 +/- 7.3 degrees C at baseline to a minimum of 16.1 +/- 3.2 degrees C at 8 weeks after treatment (p = 0.076), whereas no consistent changes were observed in the placebo group. Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge. No changes were noted in ambient digital skin temperature, total digital blood flow, finger systolic pressure or in measures of in vivo platelet activation. One subject dropped out with chest pain, but adverse effects of nausea, vomiting, headache and jaw pain were otherwise limited to the 5 days of drug infusion. CONCLUSION: Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear.

Adult↗
PubMed1991

Ventral pallidal microinjections of receptor-selective opioid agonists produce differential effects on circling and locomotor activity in rats.

Locomotor activity was investigated following microinjections of receptor-selective opioid agonists into the ventral pallidum (VP) of rats. In Expt. 1, male Long-Evans rats were treated with unilateral microinjections of the mu agonist [D-Ala2-MePhe4, Gly-ol5]-enkephalin (DAGO), the delta agonist [D-Pen2, D-Pen5]-enkephalin (DPDPE) or the kappa agonist U50,488H, and the rate and duration of circling behaviour were measured. DAGO (0.01, 0.1, 1.0 nmol) produced a dose-dependent increase in contralateral circling; pretreatment with 1.0 mg/kg naltrexone blocked the circling induced by the highest dose. The behavioral effect was largest when injections were targeted at the VP rather than structures dorsal to the VP. In contast to DAGO, intrapallidal DPDPE (0.01, 0.1, 1.0, 10.0 nmol) produced a slight increase in contralateral circling only at the highest dose and U50, 488H (0.01, 0.1, 1.0, 10.0 nmol) produced no effect. In Expt. 2, the effects of bilateral injections of DAGO, DPDPE and U50,488H were tested in photocell activity boxes. DAGO produced a dose-dependent increase in locomotor activity and this increase was decreased by 1.0 mg/kg naltrexone. A slight increase in activity was observed with the highest dose of DPDPE, and a slight decrease was observed with the highest dose of U50,488H. These findings confirm that opiate actions in the VP contribute to opiate-induced locomotion and suggest that mu and to some extent delta receptors are involved in this behavior.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Facilitory effect of delta 9-tetrahydrocannabinol on hypothalamically induced feeding.

Six male Lewis rats were tested for the effect of delta 9-tetrahydrocannabinol (delta 9-THC) on feeding evoked by electrical stimulation of the lateral hypothalamus. Treatment with delta 9-THC (0.4 mg/kg IP) decreased frequency threshold for feeding by 20.5% (+/- 4.3), causing a leftward shift in the function relating stimulation frequency to the latency to begin eating 45-mg food pellets upon stimulation onset; there was no change in the asymptotic performance that was approached with sufficiently high stimulation frequencies. Naloxone (1 and 2 mg/kg) reduced the facilitory effect of delta 9-THC, but did so at doses that can inhibit feeding in the no-drug condition. These data are consistent with evidence implicating endogenous opioids in feeding, and suggest (but do not confirm) that the facilitation of feeding by delta 9-THC may be mediated by endogenous opioids. The facilitation of stimulation-induced feeding by doses of delta 9-THC that have been found to facilitate brain stimulation reward is consistent with evidence suggesting common elements in the brain mechanisms of these two behavioral effects of medial forebrain bundle stimulation.

Animals↗
PubMed1991

Circling induced by intra-accumbens amphetamine injections.

Microinjections of d-amphetamine (5.0, 10.0 and 20.0 micrograms/0.5 microliters) into the nucleus accumbens caused reliable dose-dependent circling away from the side of injection. Injections of l-amphetamine were not effective, ruling out non-specific effects of pH, osmolarity and the like and also ruling out noradrenergic actions as explanations of the behavioral effects. Injections of d-amphetamine into the ventral caudate were less potent than those into the nucleus accumbens, suggesting nucleus accumbens rather than more dorsal tissue as the site of this behavioral effect. These data suggest that asymmetrical activation of the nucleus accumbens is a sufficient condition to induce circling behavior and raise questions for the commonly accepted view that asymmetrical activation of the caudate is a necessary condition for dopamine dependent circling behavior.

Amphetamine↗
PubMed1991

Morphine-dopamine interaction: ventral tegmental morphine increases nucleus accumbens dopamine release.

Microdialysis and high-performance liquid chromatography with electrochemical detection were used to determine extracellular levels of dopamine following ventral tegmental morphine injections into chloral hydrate-anesthetized rats. Morphine (13.2 nanomoles in 0.5 microliter of Ringer's solution) caused 50-150% increases in nucleus accumbens dopamine and metabolites; latency for the effect was on the order of 15 min with peak effects occurring in 30-50 min. Contralateral dopamine levels were influenced only minimally. These data suggest opiate receptors in or near the ventral tegmental area as sites of the opioid action that is responsible for opioid activation of the mesolimbic dopamine system.

Animals↗
PubMed1991

Effects of positive end-expiratory pressure on the gradient for venous return.

The major mechanism whereby positive end-expiratory pressure (PEEP) decreases cardiac output is believed to be a decrease in the pressure gradient for venous return. However, although PEEP increases right atrial pressure (PRA), It may also elevate mean systemic pressure (PMS), the static circulatory filling pressure that is the upstream pressure for venous return. In an intact canine preparation, we studied the effects of 15 cm H2O PEEP on cardiac output, PRA, and PMS (the equilibrium PRA during ventricular fibrillation). To examine the role of neurovascular reflexes, PEEP was applied before and after either carotid sinus and vagal denervation (CSV) or total spinal anesthesia with arterial pressure restored by epinephrine infusion (SAE). To examine the effects of PEEP-induced elevations of abdominal pressure, the abdomen was bound or widely opened and the abdominal contents exteriorized. With reflexes intact, neither binding nor opening the abdomen altered the rise in PMS during PEEP. CSV attenuated the rise in Pms by 17% (Control, 4.89 +/- 0.3 SE; CSV, 4.04 +/- 0.22 mmHg; p less than 0.01), and SAE attenuated it by 49% (Control, 4.21 +/- 0.27; SAE, 2.14 +/- 0.31 mmHg; p less than 0.00005). After either CSV or SAE, the rise in Pms was not affected by binding. PEEP decreased (Pms-PRA) only when the abdomen was bound because of a greater rise in PRA, or during SAE because of a lesser rise in Pms. Under control conditions, PEEP increased Pms and PRA equally [(PRA-Pms) = 3.89 +/- 0.26 without PEEP versus 4.13 +/- 0.29 mm Hg with PEEP]. We conclude that PEEP increases Pms by both reflex and mechanical means independent of increased abdominal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1991

Upper airway collapsibility in snorers and in patients with obstructive hypopnea and apnea.

During sleep, mild reduction in inspiratory airflow is associated with snoring, whereas obstructive hypopneas and apneas are associated with more marked reductions in airflow. We determined whether the degree of inspiratory airflow reduction was associated with differences in the collapsibility of the upper airway during sleep. Upper airway collapsibility was defined by the critical pressure (Pcrit) derived from the relationship between maximal inspiratory airflow and nasal pressure. In 10 asymptomatic snorers, six patients with obstructive hypopneas, and 10 patients with obstructive apneas, during nonrapid eye movement sleep, Pcrit ranged from -6.5 +/- 2.7 cm H2O to -1.6 +/- 1.4 and 2.5 +/- 1.5 cm H2O, respectively (mean +/- SD, p less than 0.001). Moreover, higher levels of Pcrit were associated with lower levels of maximal inspiratory airflow during tidal breathing during sleep (p less than 0.005). We conclude that differences in upper airway collapsibility distinguish among groups of normal subjects who snore and patients with periodic hypopneas and apneas. Moreover, the findings suggest that small differences in collapsibility (Pcrit) along a continuum are associated with reduced airflow and altered changes in pattern of breathing.

Airway Obstruction↗