Biomedical subjects

J E Rose

Publications and source records attributed to J E Rose.

At least 55 records · Page 3Linked to original sources

PubMed1993

Clinical evaluation of a citric acid inhaler for smoking cessation.

In this study, we evaluated the efficacy of a hand-held inhaler as an adjunct to a smoking cessation behavioral program. The inhaler delivered a citric acid aerosol with tobacco smoke flavor. Seventy-four smokers were recruited for a 3-week smoking cessation trial. During the first 12 days of the cessation period, smokers used the citric acid aerosol inhaler instead of a cigarette whenever the urge to smoke occurred. The citric acid inhaler significantly reduced CO levels and enhanced rates of smoking abstinence for those with higher than average (34.2 ppm) baseline end-expired carbon monoxide (CO) levels. Craving for cigarettes and negative affect were also alleviated by the citric acid aerosol. These results suggest that the citric acid aerosol may promote successful smoking reduction or cessation in a subgroup of smokers and relieves withdrawal symptoms such as craving for cigarettes, a symptom difficult to treat with currently available nicotine replacement techniques.

Adult↗

PubMed1993

Clinical trials using ascorbic acid aerosol to aid smoking cessation.

Sensory aspects of cigarette smoke are important for providing smoking satisfaction. In previous studies, we have found that substitution of the sensory cues of smoking with a citric acid aerosol significantly reduces craving for cigarettes and enhances smoking reduction and cessation with people trying to quit smoking cigarettes. In the current study, we conducted two clinical smoking cessation trials using an ascorbic acid aerosol as a sensory substitute. The cigarette substitute consisted of a cigarette-sized tube which delivered a fine aerosol of ascorbic acid (approx. 1 mg/puff, up to a maximum of 300 mg/day). Study 1 examined the overall effectiveness of the ascorbic acid smoking substitute device. One group of subjects which used the device and received clinical counseling was compared with another group which received only clinical counseling. The group using the device showed significantly greater abstinence rates at 3 weeks post-cessation. After the subjects stopped using the device, no difference in abstinence was detected. Study 2 was conducted to focus specifically on the role of tracheobronchial sensations in relieving craving for cigarettes. Two closely matched ascorbic acid delivery systems were compared. One device delivered fine particles of ascorbic acid that were targeted to reach the trachea, while the other delivered coarser particles of ascorbic acid that were not expected to reach the trachea or lower airways. An initial enhancement in smoking reduction was found for subjects using the fine particle device relative to those using the coarse particle device. However, by the end of treatment (5 weeks) both groups showed similar degrees of smoking reduction. For those who were abstinent from smoking at the end of treatment, craving for cigarettes and negative mood were both significantly lower for those using the fine particle device. Also, hunger for food was significantly lower in the fine particle device group. These results suggest that ascorbic acid delivered from a cigarette substitute may be effective in reducing smoking and promoting smoking abstinence.

Adult↗

PubMed1993

Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projection.

Nicotine has been found in a variety of studies to improve performance in memory tasks. This study was conducted to determine if chronic nicotine administration is useful in counteracting the working memory deficits seen after lesions of the fimbria or the medial basalocortical projection. Rats were trained to asymptotic performance on a working memory version of the radial-arm maze. Then, they were given knife cut lesions of the fimbria or the medial basalocortical projection or underwent sham surgeries. At the time of surgery, rats in each treatment group were implanted with either nicotine-containing or placebo glass and Silastic pellets. Rats with fimbria or basalocortical lesions showed a significant decline in working memory performance. Chronic nicotine significantly improved choice accuracy in both lesioned and unlesioned rats. Nicotine treatment restored performance of the lesioned rats to control levels. These data show that in addition to improving memory performance in normal rats, nicotine can counteract lesion-induced memory impairments. Nicotine also may be useful for treatment of disease-related memory impairments such as seen in Alzheimer's disease.

Animals↗

PubMed1993

Saliva nicotine as an index of plasma levels in nicotine skin patch users.

This study examined whether salivary nicotine concentrations would provide a useful index of plasma concentrations in studies of the effects of transdermal nicotine administration. Twenty-four subject smokers abstained from smoking for 12 h prior to admission to a clinical research unit ward and for 36 h while remaining confined to the ward. Three doses of nicotine skin patches were applied to different groups of subjects, and blood and saliva samples were collected at several time points. Saliva flow was stimulated by three different methods: (a) sucking on a lemon candy, (b) dissolving a sugar cube in the mouth, and (c) chewing on parafilm. Nicotine and cotinine concentrations were measured in both saliva and blood using gas chromatography. There was a high correlation between blood and saliva values of nicotine (r = 0.82). Overall, saliva nicotine concentrations were approximately 8.1 times higher than those of plasma. Saliva and blood cotinine concentrations were also highly correlated (r = 0.94), replicating results of previous studies. Results suggest that saliva nicotine may be a useful marker of nicotine intake during nicotine skin patch treatment. Saliva collection may be advantageous under conditions in which blood collection is impractical and may provide greater sensitivity because of the high concentration of nicotine in saliva relative to that in blood.

Administration, Cutaneous↗

PubMed1993

Video-assisted endoscopic thoracic ganglionectomy.

Sympathetic nerve disorders of the upper extremities can be treated by neurosurgeons using upper thoracic sympathectomy via a posterior approach. Descriptions have been published of alternative endoscopic procedures involving thermocoagulation, laser coagulation, or nonvideo-assisted ganglionectomy using equipment not widely available, with low morbidity and excellent results. The authors describe the use of an endoscopic approach to the thoracic sympathetic ganglia with systems designed for laparoscopic cholecystectomy. Thoracic ganglionectomy is reported in 22 patients with primary palmar hyperhidrosis and eight patients with reflex sympathetic dystrophy. The patients underwent double-lumen endotracheal intubation, after which 11- and 5.5-mm trocars were introduced into the chest cavity. Pneumothorax was produced with CO2 insufflation. Fiberoptic closed-circuit television was used to visualize the structures to be dissected. The parietal pleura over the heads of the first and second ribs was excised using 5-mm blunt and sharp insulated coagulating microscissors. The stellate and upper thoracic ganglia were clearly identified and dissected. The T-2 and T-3 ganglia were grasped with forceps and excised. A No. 16 French chest tube was introduced through a trocar, placed under water seal after the lungs were reinflated, and removed in the recovery room. The average hospital stay was 15.4 hours. There were no intraoperative complications. The average operating time was 30 minutes per side. Five patients had mild pleuritic pain which resolved within 2 weeks after surgery. Six (75%) of the eight patients with reflex sympathetic dystrophy had complete or partial relief of their symptoms (average follow-up period 5 months), and all patients had complete relief of hyperhidrosis (average follow-up period 8 months). Endoscopic ganglionectomy requires readily available and easily used instrumentation and provides a well-tolerated, cost-effective alternative to posterior thoracic sympathectomy for primary palmar hyperhidrosis and reflex sympathetic dystrophy.

Ganglionectomy↗

PubMed1992

Concurrent agonist-antagonist administration for the analysis and treatment of drug dependence.

Two key strategies for the treatment of drug dependence involve the use of agonists to substitute for the abused drug and the use of antagonists to block the reinforcing actions maintaining drug self-administration. A different strategy for the treatment of drug dependence is outlined, comprising the concurrent administration of an agonist and an antagonist. Concurrent administration of an agonist with an antagonist, in the proper ratio, should produce maximal occupancy of receptors and attenuation of the reinforcing actions of the abused drug. The addict would be relatively "insulated" from the reinforcing effects of the abused drug; at the same time the balance of agonist and antagonist effects is predicted to prevent withdrawal symptoms or intoxication resulting from an under- or over-stimulation of drug receptors. Advantages over the use of agonists alone and antagonists alone, and over mixed agonist-antagonist molecules, are discussed. Application of concurrent agonist-antagonist administration to the analysis of mechanisms underlying nondrug reinforcement and to the treatment of disorders involving receptor disregulation is also described.

Animals↗

PubMed1992

Persistence of chronic nicotine-induced cognitive facilitation.

Nicotine has been found in a variety of species and behavioral paradigms to improve memory performance. The beneficial effect of nicotine has been seen after both acute and chronic administration. Interestingly, improved performance has been seen 24 h after acute injection and for at least 2 weeks after chronic administration. However, it is not clear from previous studies whether the persistence of the improved performance represents a true carryover of the drug effect or is due to the behavioral experience while under nicotine's effect. The current study was conducted to determine whether the facilitating effect of nicotine on learning and memory performance could be seen after withdrawal even if there was no behavioral training during the period of chronic nicotine administration. Rats were administered nicotine chronically for 3 weeks but were not tested during that time. Starting 1 week after withdrawal they were trained on a working memory paradigm in an eight-arm radial maze. The nicotine-treated rats started out at control-like levels of performance, but showed significantly faster learning as detected by three different measures of choice accuracy. By the final phase of testing the control subjects had caught up with the nicotine-treated rats. After the acquisition phase, acute challenges with the nicotinic and muscarinic antagonists, mecamylamine and scopolamine, did not elicit any differential effects in the nicotine-treated and control groups. The current study demonstrated that nicotine-induced cognitive facilitation persists for at least 4 weeks after withdrawal and does not depend upon behavioral test experience under the influence of the drug. The mechanism for this persisting effect is not currently understood.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1991

The effects of smoking-related sensory cues on psychological stress.

Previous studies have shown that the sensory cues of cigarette smoking are important for smoking satisfaction and craving reduction. Sensory cues in the absence of pharmacological doses of nicotine have been found to be moderately satisfying and to reduce craving. The current study was conducted to determine if administration of the sensory cues of cigarette smoking with minimal nicotine would also provide relief from mild anxiety associated with anticipation of a difficult anagram test. This test has previously been shown to be sensitive to the anxiety relieving effects of cigarette smoking. Compared to the placebo control condition, the sensory condition caused a significant alleviation of the stress as measured by components of the Spielberger scale for anxiety. The addition of cigarette smoke containing 0.5 mg of nicotine to the sensory cues caused a slight though nonsignificant enhancement of the stress alleviation. These results demonstrate that sensory cues of smoking can provide similar effects as nicotine containing cigarettes with regard to stress alleviation. Previous studies had shown that sensory cues are important for the consumptive aspects of smoking (i.e., smoking satisfaction and craving reduction). The current study shows that sensory cues are important for other effects of smoking as well.

Adolescent↗

PubMed1991

Interactive effects of D1 and D2 agonists with scopolamine on radial-arm maze performance.

Pharmacological blockade of muscarinic cholinergic (ACh) receptors has been found to impair choice accuracy in a variety of tasks including the radial-arm maze. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the dopaminergic (DA) antagonist haloperidol as well as the selective D1 antagonist SCH 23390. In the current study, interactions were studied between scopolamine and selective agonists of D1 (SCH 38393) and D2 (quinpirole) receptors. Surprisingly, the D1 agonist SKF 38393 was found to significantly alleviate the scopolamine-induced choice accuracy deficit. In contrast, the D2 agonist quinpirole was not found to significantly alter the effects of scopolamine on choice accuracy but did have supra-additive effects of increasing choice latency. Both the D1 agonist SKF 38393 and the D1 antagonist SCH 23390 have been found to reverse the choice accuracy deficit caused by scopolamine and the deficit resulting from lesions of the medial projection from the basal forebrain to the cortex. Possible mechanisms for these effects are discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1991

Psychophysiological interactions between caffeine and nicotine.

The interactive effects of caffeine and nicotine were studied in twelve subjects. Mood and physiologic responses to the pharmacologic components nicotine and caffeine were measured, while controlling for the sensory/behavioral aspects of smoking and coffee drinking. Two experimental sessions presented a caffeine x nicotine design, with caffeinated or decaffeinated coffee followed at thirty-minute intervals by controlled inhalations of nicotine and nonnicotine smoke. Results showed that there was a significant interactive effect of caffeine and nicotine on subjective arousal such that nicotine decreased arousal only in the presence of caffeine. These findings extend previous work showing interactive effects of caffeine and self-titrated doses of cigarette smoke in affecting subjective arousal. The effects of nicotine on subjective arousal may, therefore, depend not only on nicotine dose, but also on the presence of caffeine. Heart rate was increased by nicotine and both systolic and diastolic blood pressures were elevated by caffeine. Caffeine also potentiated the increase in diastolic blood pressure resulting from smoke inhalations, but this occurred irrespective of nicotine dose.

Adult↗

PubMed1991

Nicotinic and muscarinic interactions and choice accuracy in the radial-arm maze.

Muscarinic acetylcholine (ACh) systems have long been known to be necessary for accurate performance in cognitive tests. Nicotinic ACh systems have been shown to be involved as well. However, there is only a limited amount of information concerning the interactions of these two branches of the ACh transmitter system. The current study was conducted to investigate the improvement in choice accuracy caused by muscarinic and nicotinic agonists and how it is affected by antagonists of these systems. Adult female Sprague-Dawley strain rats (N = 11) were trained on a working memory task in an 8-arm radial maze. Acute injections of the muscarinic and nicotinic agonists, pilocarpine (PILO, 1.0 mg/kg) and nicotine (NIC, 0.2 mg/kg), were made alone or in combination with the muscarinic and nicotinic antagonists, scopolamine (SCOP, 0.1 mg/kg) and mecamylamine (MEC, 10 mg/kg). NIC administration caused a significant improvement in choice accuracy compared with saline (p less than 0.01) and PILO caused a marginally significant improvement in choice accuracy (p less than 0.06). The combination of these nicotinic and muscarinic agonists did not cause an additive improvement. However, the improvement caused by either agonist was reversed by both nicotinic or muscarinic antagonists. This reversal was more complete for NIC than PILO despite the fact that NIC caused a greater improvement than PILO. These results suggest that muscarinic and nicotinic components of the ACh system, which are both important for cognitive function, interact in important ways. These interactions may be critical to consider when devising treatments for cognitive dysfunction associated with cholinergic hypofunction such as with Alzheimer's disease.

Animals↗

PubMed1991

Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking.

Research on smoking cessation has increasingly focussed on pharmacological aspects of nicotine and nicotine withdrawal. However, cigarette smoking also provides a characteristic set of sensory cues. These sensory aspects of smoking are important to address in that they may be potent conditioned reinforcing stimuli linked to the actions of nicotine. The repetition of the smoking act thousands of times per year by a moderately heavy smoker leads to a strong conditioned association between the sensory aspects of smoking (the putative CS) and the pharmacological effects of nicotine (the putative UCS). Strategies for disrupting CS-UCS associations may be useful in developing more effective smoking cessation treatments. These include: counterconditioning of the CS; presenting the CS alone; presenting the CS with the UCS but pharmacologically blocking the UCS; and presenting the CS and UCS in an unconnected fashion. The role of sensory cues in alleviating craving for cigarettes is discussed, and specific techniques for duplicating relevant sensory aspects of smoking without delivering significant doses of nicotine are described. The combination of nicotine and nicotinic antagonists to block primary reinforcement and hasten extinction of conditioned reinforcement is also considered.

Arousal↗

PubMed1990

Biochemical and morphological differentiation of acetylcholinesterase-positive efferent fibers in the mouse cochlea.

We have compared the biochemical expression of cholinergic enzymes with the morphological differentiation of efferent nerve fibers and endings in the cochlea of the postnatally developing mouse. Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) are present in the newborn cochlea at specific activities 63% and 25%, respectively, of their mature levels. The relative increases in ChAT, in AChE, and in its molecular forms over the newborn values start about day 4 and reach maturity by about day 10. The biochemical results correlate well with the massive presence of nerve fibers stained immunocytochemically for ChAT and AChE or enzymatically for AChE in the inner and outer hair cell regions. Ultrastructral studies, however, indicate the presence of only few vesiculated fibers and endings in the inner and outer hair cell regions. The appearance of large, cytologically mature endings occurs only toward the end of the third postnatal week. The discrepancy may be resolved in the electron microscopy using the enzymatic staining for AChE. Labeling is seen on many nonvesiculated fibers and endings in the hair cell regions, suggesting that the majority of the efferent fibers in the perinatal organ may be biochemically differentiated but morphologically immature. The results may imply that the efferents to inner and outer hair cells develop earlier than indicated by previous ultrastructral studies. Moreover, the pattern of development suggests that in the cochlea, as in other tissues, the biochemical differentiation of the efferent innervation may precede the morphological maturation.

Acetylcholinesterase↗

PubMed1990

Chronic nicotine and withdrawal effects on radial-arm maze performance in rats.

Rats were tested for choice accuracy in an eight-arm radial maze during and after chronic administration of nicotine via subcutaneously implanted glass and Silastic capsules. Nicotine administration significantly improved choice accuracy relative to controls. The effect gradually became apparent over the first 2 weeks of exposure and persisted through the third week. Surprisingly, the significant facilitation of the nicotine-treated rats relative to controls continued for 2 weeks after the end of nicotine administration. No effects of nicotine were seen on choice latency or the strategy to make adjacent arm entries.

Animals↗

PubMed1990

Cholinergic-dopaminergic interactions in cognitive performance.

Both acetylcholinergic (ACh) and dopaminergic (DA) systems have been found to be crucial for the maintenance of accurate cognitive performance. In a series of studies examining those aspects of cognitive function revealed by the radial-arm maze, we have found that these two neurotransmitter systems interact in a complex fashion. Choice accuracy deficits in the radial-arm maze can be induced by blockade of either muscarinic- or nicotinic-ACh receptors. The choice accuracy deficit induced by blockade of muscarinic receptors with scopolamine can be reversed by the DA receptor blocker, haloperidol. The specific DA D1 blocker SCH 23390 also has this effect, whereas the specific D2 blocker raclopride does not, implying that it is D1 blockade that is critical for reversing the scopolamine effect. On the other hand, the choice accuracy deficit induced by nicotinic blockade with mecamylamine is potentiated by haloperidol. This effect is also seen with the D2 antagonist raclopride, but not with the D1 antagonist SCH 23390, implying that it is the D2 receptor which is important for the potentiation of the mecamylamine effect. The relevance of the D2 receptor for nicotinic actions on cognitive function is emphasized by the finding that the selective D2 agonist LY 171555 reverses the choice accuracy deficit caused by mecamylamine. Nicotinic and muscarinic blockade are synergistic in the deficit they produce. Antagonist doses subthreshold when given alone produce a pronounced impairment when given together. This latter deficit can be reversed by the D2 agonist LY 171555. These studies have outlined the complex nature of ACh-DA interactions with regard to cognitive function. Possible neural circuits for these interactions are discussed. The effectiveness of these selective DA treatments in reversing cognitive deficits due to ACh underactivation suggests a novel approach to treating cognitive dysfunction in syndromes such as Alzheimer's disease.

Acetylcholine↗

PubMed1990

Characterization of the cognitive effects of combined muscarinic and nicotinic blockade.

Choice accuracy performance in the radial-arm maze is dependent upon the integrity of both the nicotinic and muscarinic cholinergic receptors. Pharmacological blockade of either of these subtypes of cholinergic receptors with mecamylamine or scopolamine impairs choice accuracy in the radial-arm maze. We have previously demonstrated that the performance deficit caused by muscarinic blockade is exacerbated in at least an additive fashion by coadministration of the nicotinic antagonist, mecamylamine. In the present study, it was found that mecamylamine and scopolamine act together in a greater than additive fashion in disrupting radial-arm maze choice accuracy. When doses of these drugs which do not by themselves cause significant impairments in choice accuracy are given together, they induce a pronounced impairment. Previous results have shown that the adverse effects of nicotinic blockade could be reversed by the dopaminergic D2 agonist LY 171555. In this study, this drug was found to attenuate the cognitive impairment caused by combined nicotinic and muscarinic blockade. On the other hand, the dopaminergic D1 antagonist SCH 23390 which has previously been shown to reverse the adverse effects of muscarinic blockade was not found in this study to attenuate the impairment of combined nicotinic and muscarinic blockade. Since combined nicotinic and muscarinic blockade approximates generalized cholinergic underactivation, treatments like LY 171555, which attenuate the adverse effects of this combined blockade, may be useful in treating syndromes like Alzheimer's disease, which are characterized by generalized cholinergic loss.

Animals↗

PubMed1990

The use of flavor in cigarette substitutes.

Cigarette smokers identify flavor as an important factor in the pleasure derived from smoking and for their choice of cigarette brand. The issue of cigarette flavor has received a great deal of study by cigarette manufacturers but relatively little by academic investigators. The paucity of literature is particularly acute in terms of the importance of flavor in cigarette substitutes, which are used to help people to reduce or quit smoking. In the current study, five different types of flavors added to a plastic cigarette substitute were assessed in experienced smokers. There were two menthol-like flavors and three tobacco-like flavors. Two groups of smokers were tested: menthol smokers and "regular" (non-menthol) smokers. Both types of smokers liked the two menthol flavors significantly more than placebo and rated the menthol flavors and the cigarette flavor as significantly more satisfying than placebo. Craving was differentially reduced in the two groups of smokers. Menthol smokers showed a small reduction in craving with the placebo, with a significant enhancement of this reduction seen with the addition of the "EZ Quit" menthol flavor.

Adult↗

PubMed1990

Development of a citric acid aerosol as a smoking cessation aid.

The satisfaction derived from smoking depends not only on the pharmacological effects of nicotine but also the sensory stimulation from smoke inhalation, particularly the tracheal 'scratch'. In a previous study, we found that a citric acid aerosol produces a tracheal 'scratch' and provides some of the same satisfaction as cigarette smoke. In the present study, we evaluated a new pocket-sized device for delivering a citric acid aerosol and examined some of the important variables for providing a satisfying substitute for cigarettes. In the first experiment, volunteers who smoked at least 10 cigarettes per day compared a citric acid aerosol (either alone or with flavor additives) to a cigarette and a placebo. The addition of cigarette smoke flavor was found to best enhance the satisfaction provided by the citric acid aerosol. In the second experiment, smokers were given compact citric acid inhalers to use throughout 8 h of cigarette deprivation. The degree of satisfaction was highly correlated with the intensity of throat sensation provided by the aerosol. This citric acid aerosol inhaler may provide a useful tool for smokers while trying to quit smoking.

Aerosols↗