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Biomedical subjects

E F Domino

Publications and source records attributed to E F Domino.

At least 19 recordsLinked to original sources

Regional cerebral blood flow effects of nicotine in overnight abstinent smokers.

BACKGROUND: Most people agree that dependence to tobacco is mediated by the effects of nicotine on the central nervous system, albeit the neural pathways involved are not clearly delineated. We investigated the effect of nasal nicotine spray on regional cerebral blood flow (rCBF) in a sample of habitual smokers, with H2 15O and positron emission tomography (PET). METHODS: Eighteen volunteer smokers were studied after 12 hours of smoking deprivation. Regional cerebral blood flow measures were obtained with PET and 50 mCi H2 15O in six consecutive scans. Nicotine spray and a placebo spray were administered in a single-blind design, preceded and followed by baseline studies. Images were coregistered and anatomically standardized. Square (9-mm side) regions of interest were placed in 10 preselected brain regions, bilaterally. The effects of the experimental condition and gender were tested with two-way repeated-measures analysis of variance in each of the regions studied. RESULTS: Nicotine reduced rCBF in the left anterior temporal cortex and in the right amygdala. Increases were noted in the right anterior thalamus. CONCLUSIONS: In habitual smokers after overnight abstinence, nicotine induced differing effects on regional blood flow relative to whole brain blood flow. Increases were observed in the thalamus, a region rich in nicotinic receptors, and reductions in limbic and paralimbic (amygdala, anterior temporal cortex) regions.

Adolescent↗

Nicotine induced behavioral locomotor sensitization.

1. Nicotine behavioral sensitization of locomotor activity was investigated in adult female Sprague Dawley rats. Five different experiments were performed with nicotine in various doses of 0.1, 0.32, or 1.0 mg/kg i.p. These included: 1) effects of daily nicotine for 6 days, 2) effects of once per week nicotine for 3 weeks, 3) effects of MK-801 on nicotine-induced locomotor activity, 4) effects of dexamethasone on nicotine-induced locomotor activity, 5) induction of tolerance to nicotine-induced locomotor sensitization and lack of cross tolerance to caffeine. 2. Locomotor activity was measured with a photoelectric computerized system. The first dose of nicotine (0.32 mg/kg) induced marked locomotor depression. Once daily injection of 0.32 mg/kg of nicotine for 6 days produced tolerance to its depressant effects and sensitized the rats to its stimulant effects. Three once weekly doses of 0.32 mg/kg of nicotine also produced tolerance to its depressant effects and some locomotor stimulation. 3. Daily pretreatment for 5 days with a dose of 0.18 mg/kg of MK-801 i.p. partially antagonized the locomotor depressant and stimulant actions of nicotine. 4. Dexamethasone (1 mg/kg i.p.) daily pretreatment barely reduced nicotine locomotor depression and only very slightly enhanced locomotor stimulation. 5. Accumulating doses of 0.32 and 1.0 mg/kg b.i.d. of nicotine produced tolerance to its locomotor stimulant effects in rats previously sensitized to 0.32 mg/kg. There was no cross-tolerance to 32 mg/kg of caffeine citrate in previously sensitized animals tolerant to the stimulant effects of nicotine.

Animals↗

Nicotine and tobacco dependence: normalization or stimulation?

Nicotine and tobacco use produces mixed stimulant and depressant effects on various brain functions in animals and human beings. Results of electroencephalographic studies indicate that some tobacco smokers after 10-24 h of tobacco deprivation exhibit a decrease in dominant alpha rhythm, which, immediately after smoking, increases toward that of nonsmokers. This is evidence that tobacco smoking in smokers involves normalization of brain activity. Results of other studies of acute smoking effects in smokers show an increase in dominant alpha rhythm greater than that of nonsmokers. This is evidence that tobacco smoking produces stimulation of brain activity in smokers.

Alpha Rhythm↗

Allergic reactions to isosulfan blue during sentinel node biopsy--a common event.

BACKGROUND: Sentinel lymph node (SLN) dissection in the management of high-risk melanoma and other cancers, such as breast cancer, has recently increased in use. The procedure identifies an SLN by intradermal or intraparenchymal injection of an isosulfan blue dye, a radiocolloid, or both around the primary malignancy. METHODS: At the time of selective SLN mapping, 3 to 5 mL of isosulfan blue was injected either intradermally or intraparenchymally around the primary malignancy. From October 1997 to May 2000, 267 patients underwent intraoperative lymphatic mapping with the use of both isosulfan 1% blue dye and radiocolloid injection. Five cases with adverse reactions to isosulfan blue were reviewed. RESULTS: We report 2 cases of anaphylaxis and 3 cases of "blue hives" after injection with isosulfan blue of 267 patients who had intraoperative lymphatic mapping by the procedure described above. The 2 patients with anaphylaxis experienced cardiovascular collapse, erythema, perioral edema, urticaria, and uvular edema. The blue hives in 3 patients resolved and transformed to blue patches during the course of the procedures. CONCLUSIONS: The incidence of allergic reactions in our series was 2.0%. As physicians expand the role of SLN mapping, they should consider the use of histamine blockers as prophylaxis and have emergency treatment readily available to treat the life- threatening complication of anaphylactic reaction.

Adult↗

Nicotine effects on regional cerebral blood flow in awake, resting tobacco smokers.

The hypothesis for this research was that regional cerebral blood flow (rCBF) would increase following nasal nicotine administration to overnight abstinent tobacco smokers in relationship to the known brain distribution of nicotinic cholinergic receptors (nAChRs). Nine male and nine female healthy adult smokers were studied. They abstained overnight from tobacco products for 10 or more hours prior to study the next morning. Nicotine nasal spray was given in doses of 1-2.5 mg total with half in each nostril while the subject was awake and resting in a supine position. Oleoresin of pepper solution in a similar volume was used as an active placebo to control for the irritating effects of nicotine. Both substances were given single blind to the subjects. Positron emission tomography (PET) with H(2)(15)O was used to measure rCBF. The data from each subject volunteer were normalized to global activity to better assess regional brain changes. Both nasal nicotine and pepper spray produced similar increases in CBF in somesthetic area II, consistent with the irritant effects of both substances. The mean rCBF effects of nasal pepper were subtracted from those of nasal nicotine to determine the actions of nicotine alone. The latter produced increases in rCBF in the thalamus, pons, Brodman area 17 of the visual cortex, and cerebellum. Some brain areas that contain a large number of nAChRs, such as the thalamus, showed an increase in CBF. Other areas that have few nAChRs, such as the cerebellum, also showed an increase in relative CBF. The hippocampal/parahippocampal areas showed greater regional decreases (left) and lesser increases (right) in CBF that correlated with the increase in plasma arterial nicotine concentrations. The results obtained indicate complex primary and secondary effects of nicotine in which only some regional brain CBF changes correlate with the known distribution of nAChR. No gender differences were noted.

Administration, Intranasal↗

Effects of tobacco smoking on topographic EEG and Stroop test in smoking deprived smokers.

1. Quantitative electroencephalography (EEG) was used to measure human brain electrical changes produced by tobacco deprivation and smoking. Sixteen scalp cortical recording sites monitored regional changes in brain activity. 2. The quantitative EEG was subdivided into delta, theta, alpha1, alpha2, beta1 and beta2 bands for topographic mapping. A demanding version of the Stroop test was used to determine tobacco smoking effects on attention. The version used was more difficult than that used in previously reported studies. 3. Healthy drug and substance free adult male and female volunteers were divided into nonsmoker (n=7) and smoker (n=7) groups according to their smoking status. They were instructed to abstain from tobacco products for at least 12 hr overnight before the next morning's experiment. 4. EEG was recorded before and after smoking either a fake placebo cigarette for nonsmokers or the cigarette of their choice for smokers. Subjects were also asked to perform the Stroop test before and after smoking the placebo or tobacco cigarette. 5. The results showed that tobacco smoking significantly depressed delta and increased alpha2 and beta1 activity and slightly increased the Stroop effect. Although smoking one cigarette stimulated brain electrical activity of smoking deprived smokers, it did not improve performance on a difficult Stroop test.

Adult↗

Effects of nicotine on regional cerebral glucose metabolism in awake resting tobacco smokers.

Eleven healthy tobacco smoking adult male volunteers of mixed race were tobacco abstinent overnight for this study. In each subject, positron emission tomographic images of regional cerebral metabolism of glucose with [18F]fluorodeoxyglucose were obtained in two conditions in the morning on different days: about 3min after approximately 1-2mg of nasal nicotine spray and after an equivalent volume of an active placebo spray of oleoresin of pepper in a random counterbalanced design. A Siemens/CTI 931/08-12 scanner with the capability of 15 horizontal brain slices was used. The images were further converted into a standard uniform brain format in which the mean data of all 11 subjects were obtained. Images were analysed in stereotactic coordinates using pixel-wise t statistics and a smoothed Gaussian model. Peak plasma nicotine levels varied three-fold and the areas under the curve(0-30min) varied seven-fold among the individual subjects. Nicotine caused a small overall reduction in global cerebral metabolism of glucose but, when the data were normalized, several brain regions showed relative increases in activity. Cerebral structures specifically activated by nicotine (nicotine minus pepper, Z score >4.0) included: left inferior frontal gyrus, left posterior cingulate gyrus and right thalamus. The visual cortex, including the right and left cuneus and left lateral occipito-temporal gyrus fusiformis, also showed an increase in regional cerebral metabolism of glucose with Z scores >3. 6. Structures with a decrease in regional cerebral metabolism of glucose (pepper minus nicotine) were the left insula and right inferior occipital gyrus, with Z scores >3.5. Especially important is the fact that the thalamus is activated by nicotine. This is consistent with the high density of nicotinic cholinoceptors in that brain region. However, not all brain regions affected by nicotine are known to have many nicotinic cholinoceptors. The results are discussed in relation to the cognitive effects of nicotine.

Administration, Intranasal↗

Nicotine alone and in combination with L-DOPA methyl ester or the D(2) agonist N-0923 in MPTP-induced chronic hemiparkinsonian monkeys.

Nicotine, the soluble methyl ester of L-DOPA, and the D(2) agonist N-0923 were given alone and in combination im to five hemiparkinsonian monkeys. Daily nicotine in doses of 32-320 micrograms/kg for 6 days each, surprisingly, had slight effects on motor activity. When combined with N-0923, nicotine did not further enhance its effects. However, L-DOPA methyl ester plus nicotine produced greater contraversive circling than L-DOPA methyl ester plus 0.9% NaCl. Similar effects were obtained on significant motor movements of both the affected (contralateral) and normal (ipsilateral) arm and hand. The results indicate that nicotine is synergistic with l-DOPA methyl ester, but not with the postsynaptic D(2) agonist N-0923.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Arterial/venous plasma nicotine concentrations following nicotine nasal spray.

BACKGROUND AND OBJECTIVES: Arterial (A) and venous (V) plasma nicotine and cotinine concentrations were measured after nasal nicotine spray in tobacco smokers of both genders. The hypothesis for this research was that a greater A/V difference in plasma nicotine would be present in males than females because males have greater skeletal muscle mass to bind nicotine. SUBJECTS AND METHODS: Nine male and nine female healthy adult smokers were studied. They all abstained from use of tobacco overnight for 10 h or more prior to the study. Nicotine nasal spray was given in doses of 1-2.5 mg total, with half in each nostril while the subject was supine. Both A and V blood samples were obtained prior to and 3, 6, 10, 15, 20, and 30 min post-nasal nicotine spray. RESULTS AND CONCLUSIONS: Nasal nicotine administration produced greater A than V plasma levels. There were no gender differences in A/V nicotine concentrations, disproving the above hypothesis, suggesting that other physiochemical factors besides skeletal muscle mass must be involved. Heart rate increases correlated well with arterial plasma nicotine levels (r = 0.77). Males had less variance than females in the expected increase in arterial plasma nicotine concentrations with increased number of nasal sprays. Although there was considerable overlap, mean A cotinine concentrations were consistently slightly larger than V concentrations.

Administration, Intranasal↗

A further study on asymmetric cross-sensitization between MK-801 and phencyclidine-induced ambulatory activity.

Our previous study found that MK-801-sensitized rats showed cross-sensitization to the locomotor stimulant effects of phencyclidine, but phencyclidine sensitized rats did not show cross-sensitizaton to MK-801. This study was designed to determine whether the asymmetric cross-sensitization was due to injection-environment conditioning or possibly reduced phencyclidine-like effects following further repeated injections of phencyclidine. Adult female Sprague-Dawley rats were used in this study, and their activity was assessed with an automated photoelectric system. Results confirmed the early finding that four daily injections of phencyclidine (3.2 mg/kg) or MK-801 (0.32 mg/kg) produced locomotor sensitization, and that the two drugs showed asymmetric cross-sensitization. Moreover, injection-environment conditioning was ruled out as a possible cause for cross-sensitization from MK-801 to phencyclidine, and possibly reduced phencyclidine-like effects following further repeated injections was also ruled out as a cause for the failure of cross-sensitization from phencyclidine to MK-801. These additional results further confirm our previous finding, and indicate that there are significant differences in the neural mechanisms underlying phencyclidine- and MK-801-induced sensitization.

Animals↗

Effects of tobacco smoking on the human pupil.

OBJECTIVE: Determine the effects of tobacco cigarette or sham placebo-smoking on pupil diameter. SUBJECTS: Ten non-smokers and 10 tobacco smokers (all healthy, drug free adults) were studied while resting in a comfortable lounger. METHODS: Tobacco smokers abstained from smoking and all subjects abstained from caffeine-containing products for at least 8 h prior to testing. The smokers each smoked one tobacco cigarette, and the non-smokers each inhaled air through an unlit sham cigarette. Right pupil diameter, heart rate, systolic and diastolic blood pressure were measured before and after sham- or tobacco-smoking in each subject. Pupil size was measured from a colored photograph taken with a Polaroid camera equipped with a high-speed flash with the subject in a standardized, dimly lit quiet room. RESULTS: There was no significant difference in baseline pupil diameter between non-smokers and smokers prior to sham- or tobacco-smoking. After sham- or tobacco-smoking, both non-smokers and smokers showed slight but statistically significant pupillary constriction. CONCLUSIONS: Shortly after smoking one tobacco cigarette, pupillary constriction was greater than after sham-smoking.

Adult↗

MPTP-Induced hemiparkinsonism in nonhuman primates 6-8 years after a single unilateral intracarotid dose.

Five female adult Macaca nemestrina monkeys, given a unilateral intracarotid (ic) infusion of 2.3-3.5 mg of MPTP-HCl, were studied for 6-8 years. Two to 3 days after MPTP, the animals developed hemiparkinsonism characterized by rigidity and flexed posture of the arm contralateral to the side of infusion with episodes of tremor, circling ipsilateral to the lesioned side, a slight balance disturbance, and stooped posture. Rating of parkinsonian features 4 months after ic infusion, and yearly thereafter, did not show any statistically significant changes. The animals maintained their usual appetite and body weight increased normally. Each animal responded to l-DOPA methyl ester with decreased parkinsonian signs and symptoms and increased contralateral turning. In contrast, after control vehicle administration, the animals continued to have the same parkinsonian signs and predominant ipsilateral turns. In three of the five monkeys, contralateral turns after vehicle significantly increased after 6-8 years. Unilateral intracarotid MPTP induced asymmetric motor behavior that remained stable after 6-8 years. Animals that showed an increased frequency of contralateral circling after control vehicle showed a decrease in contralateral turns after l-DOPA methyl ester, suggesting neuroplastic changes over the years.

Animals↗

Trihexyphenidyl potentiation of L-DOPA: reduced effectiveness three years later in MPTP-induced chronic hemiparkinsonian monkeys.

The effects of a combination of trihexyphenidyl and L-DOPA methyl ester given i.m. were studied 3-5 years after MPTP induced hemiparkinsonism in five female adult Macaca nemistrina monkeys. Three years later, these studies were repeated to determine if the drug combination was equally effective. Although the combination of trihexyphenidyl and L-DOPA produced potentiation in both studies, 3 years later it was quantitatively less. This was due primarily to the reduced effectiveness of L-DOPA methyl ester in a dose of 12.5 mg/kg i.m. Even though the combination was less effective in subsequent years, the animals continued to show the same clinical signs of hemiparkinsonism. Reduced effectiveness of the drug combination does not appear to be due to a lessening of MPTP-induced hemiparkinsonism, but rather to the reduced effectiveness of L-DOPA.

Animals↗

Effects of tobacco smoking and abstinence on middle latency auditory evoked potentials.

OBJECTIVE: To evaluate the effects of tobacco cigarette smoking and overnight abstinence on middle latency auditory evoked potentials among smokers and nonsmokers. METHODS: Groups of 9 to 10 adult male and female nonsmokers and smokers participated in the study. Each person volunteered for two laboratory sessions conducted in the early afternoon on 2 separate days. Smokers abstained from tobacco products 6 to 15 hours before the abstinent session and maintained their usual smoking behavior before the smoking session. The nonsmokers had a similar laboratory experience but sham smoked by means of inhaling air. Middle latency auditory evoked potentials were recorded from Cz to both ears as reference. RESULT: The latencies of the Na and Pa potentials during the smoking session were significantly (p < 0.01) shorter than those in abstinent smokers and nonsmokers. After smoking, peak-to-trough amplitudes for the V-Na, Na-Pa, and Pa-Nb potentials were larger than those after abstinence and significantly larger than those among nonsmokers. CONCLUSIONS: The shorter latencies of the middle latency brain wave components in the smoking session suggest faster processing of sensory information after cigarette smoking. Larger Pa amplitudes after cigarette smoking suggest a higher arousal level than that among partially abstinent smokers and nonsmokers.

Adult↗