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Biomedical subjects

J R Taylor

Publications and source records attributed to J R Taylor.

At least 73 records · Page 4Linked to original sources
PubMed1998

Prefrontal cortical involvement in phencyclidine-induced activation of the mesolimbic dopamine system: behavioral and neurochemical evidence.

Acute administration of phencyclidine to rats potently activates mesocorticolimbic dopaminergic neurons. The activation of dopamine release and utilization in the prefrontal cortex and nucleus accumbens are associated with profound cognitive impairment and hyperlocomotion, respectively. This dopaminergic activation by phencyclidine is not mediated by direct effects on the cell body regions of the dopamine neurons; however, phencyclidine augments dopamine release locally in the terminal fields. In the present study, the possible involvement of the prefrontal cortex in mediating activation of the mesolimbic dopamine system by phencyclidine was examined. Ibotenic acid lesions of the prefrontal cortex attenuated the biochemical activation of the mesolimbic dopamine neurons by PCP, and prefrontal lesions sharply blunted phencyclidine-, but not amphetamine- or novelty-, induced hyperlocomotion. In addition, injection of phencyclidine directly into the prefrontal cortex increased dopamine utilization in the nucleus accumbens and induced hyperlocomotion. In summary, these studies show that phencyclidine activates the mesolimbic pathway through a mechanism in the prefrontal cortex, possibly by disinhibiting the cortical circuit and activating corticofugal glutamatergic release in the ventral tegmental area.

Animals↗
PubMed1998

A comparison of the effects of clonidine and CNQX infusion into the locus coeruleus and the amygdala on naloxone-precipitated opiate withdrawal in the rat.

Both the locus coeruleus (LC) and the amygdala have been implicated in aspects of opiate dependence and withdrawal. The LC is known to be one of the most sensitive sites for precipitating withdrawal behaviors after local opiate antagonist infusions in morphine-dependent subjects. The amygdala is also known to mediate antagonist-induced withdrawal behaviors and aversive motivational states. The goal of the present study was to evaluate directly the ability of noradrenergic agonists and glutamatergic antagonists to attenuate naloxone-precipitated withdrawal behaviors when infused into the LC or the central nucleus of the amygdala (CeA). The alpha-2-noradrenergic agonists clonidine or ST-91 were infused into the CeA to compare the effects of noradrenergic activation in the CeA to the attenuation of withdrawal previously observed in rats infused with clonidine into the LC, since the LC and CeA are known to contain co-localized opiate and noradrenergic receptors. The effects of microinfusions of the non-NMDA excitatory amino acid antagonist 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) were also infused into the LC and CeA since opiate withdrawal is associated with increased glutamatergic transmission. Intra-CeA clonidine or ST-91 (2.4 microg/0.5 microl or 1.0 microl) produced significant reductions primarily in the occurrence of irritability. Conversely, intra-CeA or intra-LC infusions of CNQX (2.5 microg/0.5 microl) significantly attenuated naloxone-precipitated withdrawal, an effect similar to the attenuation previously observed after intra-LC clonidine infusions. These data demonstrate the specific behavioral effects of altering glutamatergic and noradrenergic neurotransmission in the LC or CeA during naloxone-precipitated opiate withdrawal. Elucidation of the neuroanatomical circuitry involved in opiate withdrawal should increase our understanding of the neuroadaptations associated with drug dependence and subsequent withdrawal behavior.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1998

Dorsal root ganglion injuries in 109 blunt trauma fatalities.

In an autopsy study of 180 cervical spines, 109 were from victims of fatal blunt injury. A search was made for injuries to the dorsal root ganglia. The whole cervical spines, from the skull base to T1, were formalin fixed, deep frozen and sagittally sectioned on a specially adapted band saw in 2.5 mm thick slices. In 15 of the 109 fatally injured individuals, 44 examples of interstitial haemorrhage into a dorsal root ganglion (DRG) were found. This was sometimes accompanied by neural tissue disruption, visible only on histological study. The intraneural DRG haemorrhage was found in 13.8 per cent of all the injured individuals, but this prevalence rose to 34.5 per cent when only those (29) individuals surviving the injury between 2 h and 7 days were considered. The possible relevance of such injuries, in survivors of injury, to acute and chronic pain syndromes is discussed.

Adolescent↗
PubMed1998

Subchronic phencyclidine administration increases mesolimbic dopaminergic system responsivity and augments stress- and psychostimulant-induced hyperlocomotion.

Previous studies have shown that repeated exposures to phencyclidine (PCP) induces prefrontal cortical dopaminergic and cognitive deficits in rats and monkeys, producing a possible model of schizophrenic frontal cortical dysfunction. In the current study, the effects of subchronic PCP exposure on forebrain dopaminergic function and behavior were further explored. Prefrontal cortical dopamine utilization was reduced 3 weeks after subchronic PCP administration, and the cortical dopaminergic deficit was mimicked by repeated dizocilpine exposure. In contrast, stress- and amphetamine-induced hyperlocomotion, behavior believed to be mediated by activation of mesolimbic dopamine transmission, was enhanced after PCP exposures. Furthermore, haloperidol-induced increases in nucleus accumbens dopamine utilization were larger in magnitude in PCP-treated rats relative to control subjects. These data are the first to demonstrate that repeated exposures to PCP causes prefrontal cortical dopaminergic hypoactivity and subcortical dopaminergic hyper-responsivity in rats, perhaps mimicking alterations in dopaminergic transmission that underlie the behavioral pathology of schizophrenia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector.

An adeno-associated virus (AAV) vector, expressing genes for human tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC), demonstrated significantly increased production of dopamine in 293 (human embryonic kidney) cells. This bicistronic vector was used to transduce striatal cells of six asymptomatic but dopamine-depleted monkeys which had been treated with the neurotoxin MPTP. Striatal cells were immunoreactive for the vector-encoded TH after stereotactic injection for periods up to 134 days, with biochemical effects consistent with dopamine biosynthetic enzyme expression. A subsequent experiment was carried out in six more severely depleted and parkinsonian monkeys. Several TH/aadc-treated monkeys showed elevated levels of dopamine near injection tracts after 2.5 months. Two monkeys that received a beta-galactosidase expressing vector showed no change in striatal dopamine. Behavioral changes could not be statistically related to the vector treatment groups. Toxicity was limited to transient fever in several animals and severe hyperactivity in one animal in the first days after injection with no associated histological evidence of inflammation. This study shows the successful transfection of primate neurons over a period up to 2.5 months with suggestive evidence of biochemical phenotypic effects and without significant toxicity. While supporting the idea of an in vivo gene therapy for Parkinson's disease, more consistent and longer lasting biochemical and behavioral effects will be necessary to establish the feasibility of this appraoch in a primate model of parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Detection of drug use in a methadone maintenance clinic: sweat patches versus urine testing.

AIMS: To evaluate the novel use of sweat patches in outpatients attending a methadone maintenance clinic. DESIGN: Assessment of inter-patch reliability and validity of patch results compared to urine tests at the start and end of the patch period. Semi-structured questionnaire on patients' opinion of the patches. Randomized cross-over trial comparing illicit drug use during the week that the patch was worn with a control period. SETTING: Methadone maintenance outpatient clinic in a deprived urban area. PARTICIPANTS: Forty-eight patients with a diagnosis of opiate addiction prescribed methadone for a median of 5 years. MEASUREMENTS: Analysis of urine and patch tests by standard methods for methadone, opiates, morphine (heroin metabolite) and benzoylecgonine (cocaine metabolite). FINDINGS: There was good inter-patch reliability between arm and side patches for methadone (all positive), opiates (k = 0.8) and morphine (k = 1.0) but only moderate agreement for benzoylecgonine (k = 0.49). There was good agreement between the sweat patches and urine tests for methadone (all positive), opiates (k = 1.00) and morphine (k = 0.8), but again only moderate agreement for benzoylecgonine (k = 0.50). The patches were well tolerated and the main side effect was minor irritation. The majority of men preferred a urine test while more women preferred a sweat patch. There was no evidence of reduced use of illicit drugs the period that the patch was worn. CONCLUSION: Sweat patches are reliable and give valid results for patients on maintenance methadone. There are few side effects and it is practical to use them in busy outpatient clinics. They are preferred by some patients but there was no evidence that they altered behaviour.

Adult↗
PubMed1998

Medication bezoars: a literature review and report of a case.

OBJECTIVE: To describe a case of a medication bezoar and to review the clinical presentation, diagnosis, risk factors, pathogenesis, complications, and treatment of medication bezoars. DATA SOURCES AND STUDY SELECTION: A MEDLINE search (January 1966-December 1997) of the English-language literature pertaining to bezoars was performed. These articles were scanned, and literature specifically discussing medication bezoars was selected. Additionally, the reference sections of pertinent review and case reports were scanned for additional relevant literature. DATA SYNTHESIS: Bezoars are concretions of foreign material within the body. In the case of medication bezoars, these concretions occur within the digestive tract and are composed of medications and/or medication vehicles. Rarely, however, is bezoar formation solely due to a medication. In nearly all reported cases the patient had one or more significant risk factors that contributed to bezoar formation. The exact method by which medications bezoars form is dependent on the particular type or combination of medications involved. Bezoar formation may be associated with significant complications for the patient due to the presence of the bezoar and because of the effects of the medication within the bezoar. Treatment of medication bezoars depends largely on the location and the cause of the bezoar. CONCLUSIONS: Medication bezoars are a rare but potentially serious complication of medication use in certain patients. These patients often present with signs and symptoms consistent with an obstruction of the gastrointestinal tract and represent an even greater diagnostic challenge due to the rarity of this complication. These patients also face significant complications from both the bezoar and the medication within the bezoar. To date, treatment of medication bezoars involves mainly physical manipulation of the bezoar through lavage, endoscopic removal, or, in most cases, surgical removal.

Aged↗
PubMed1998

Diagnosis of stroke.

The determination that a patient has suffered a stroke is readily based on the clinical criteria along with the additional ancillary procedures discussed. The diagnosis is not complete, however, until the etiology has been found, for only then can rational therapy proceed.

Adult↗
PubMed1997

Opposite modulation of opiate withdrawal behaviors on microinfusion of a protein kinase A inhibitor versus activator into the locus coeruleus or periaqueductal gray.

Chronic opiate administration upregulates the cAMP pathway in the locus coeruleus (LC). This adaptation is thought to increase the electrical excitability of LC neurons and contribute to the dramatic increase in LC firing induced by opioid receptor antagonists in opiate-dependent animals. The goal of the present study was to evaluate directly a role of the cAMP pathway in opiate withdrawal behaviors by studying, in vivo, whether withdrawal is influenced by intra-LC infusion of compounds known to activate or inhibit protein kinase A (PKA). Infusions into amygdala or periaqueductal gray (PAG) were studied for comparison. In one series of experiments the effect of intra-LC, intra-amygdala, or intra-PAG infusions of the PKA inhibitor Rp-cAMPS on naloxone-precipitated withdrawal from morphine was examined. Intra-LC infusions of Rp-cAMPS significantly attenuated several prominent behavioral signs of morphine withdrawal. Intra-PAG infusions of Rp-cAMPS also significantly attenuated opiate withdrawal behaviors, although different behaviors were affected. In contrast, intra-amygdala infusions of Rp-cAMPS were without significant effect. In a second series of experiments the effect of intra-LC or intra-PAG infusions of the PKA activator Sp-cAMPS on behavior in nondependent drug-naive animals was determined. Sp-cAMPS infusions into either brain region induced a quasi-withdrawal syndrome, but the observed behaviors differed between the two groups. Analysis of the phosphorylation state of tyrosine hydroxylase, a well characterized substrate for PKA, confirmed the ability of Rp-cAMPS and Sp-cAMPS to inhibit and activate, respectively, PKA activity in vivo. Together, these data provide direct evidence for involvement of the cAMP-PKA system in the LC, as well as in the PAG, in opiate withdrawal and withdrawal-related behaviors.

Amygdala↗
PubMed1997

Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance.

Although previous research has emphasized the beneficial effects of dopamine (DA) on functions of the prefrontal cortex (PFC), recent studies of animals exposed to mild stress indicate that excessive DA receptor stimulation may be detrimental to the spatial working memory functions of the PFC (Arnsten and Goldman-Rakic, 1990; Murphy et al., 1994, 1996a,b, 1997). In particular, these studies have suggested that supranormal stimulation of D1 receptors may contribute to the detrimental actions of DA in the PFC (Murphy et al., 1994, 1996a). The current study directly tested this hypothesis by examining the effects of infusing a full D1 receptor agonist, SKF 81297, into the PFC of rats performing a spatial working memory task, delayed alternation. SKF 81297 produced a dose-related impairment in delayed-alternation performance. The impairment was reversed by pretreatment with a D1 receptor antagonist, SCH 23390, consistent with drug actions at D1 receptors. SCH 23390 by itself had no effect on performance, although slightly higher doses impaired performance (Murphy et al., 1994, 1996a). There was a significant relationship between infusion location and drug efficacy; animals with cannulae anterior to the PFC were not impaired by SKF 81297 infusions. Taken together, these results demonstrate that supranormal D1 receptor stimulation in the PFC is sufficient to impair PFC working memory function. These cognitive data are consistent with recent electrophysiological studies of D1 receptor mechanisms affecting the PFC (Williams and Goldman-Rakic, 1995; Yang and Seamans, 1996). Increased D1 receptor stimulation during stress may serve to take the PFC "off-line" to allow posterior cortical and subcortical structures to regulate behavior, but may contribute to the vulnerability of the PFC in many neuropsychiatric disorders.

Animals↗
PubMed1997

Enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long-term administration of phencyclidine.

The effects of the psychotomimetic drug phencyclidine on the neurochemistry and function of the prefrontal cortex in vervet monkeys were investigated. Monkeys treated with phencyclidine twice a day for 14 days displayed performance deficits on a task that was sensitive to prefrontal cortex function; the deficits were ameliorated by the atypical antipsychotic drug clozapine. Repeated exposure to phencyclidine caused a reduction in both basal and evoked dopamine utilization in the dorsolateral prefrontal cortex, a brain region that has long been associated with cognitive function. Behavioral deficits and decreased dopamine utilization remained after phencyclidine treatment was stopped, an indication that these effects were not simply due to direct drug effects. The data suggest that repeated administration of phencyclidine in monkeys may be useful for studying psychiatric disorders associated with cognitive dysfunction and dopamine hypofunction in the prefrontal cortex, particularly schizophrenia.

Animals↗
PubMed1997

Severe long-term 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the vervet monkey (Cercopithecus aethiops sabaeus).

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces parkinsonian neurochemical and functional deficits in human and non-human primates. The utility of MPTP-induced parkinsonism in monkeys as an animal model of Parkinson's disease would be greater if it produced a persistent and stable behavioural syndrome so that the effects of novel therapeutic treatments can be accurately assessed. Further, the claim that many species including primates spontaneously recover from MPTP is a significant difference from idiopathic Parkinson's disease. This experiment focused on the long-term (six months) persistence of behavioural deficits in severely and moderately parkinsonian monkeys. The severity of the syndrome was based on a quantitative and objective measure of parkinsonism. Adult male African green (vervet) monkeys (Cercopithecus aethiops sabaeus) were treated with MPTP (cumulative dose 2.5 mg/kg over five days), and six were saline-control treated. MPTP-treated subjects were examined in two groups: those that were severely parkinsonian ("severe" group, n = 11) and those that were moderately impaired ("moderate" group, n = 5) the month after treatment. Summary factor scores were examined reflecting abnormal ("parkinsonian") behaviour and normal "healthy" behaviour. Subjects that displayed severe parkinsonism the month after MPTP were found to show stable and severe parkinsonism for the time period studied. In contrast, the group of animals that initially were moderately parkinsonian did not show a stable deficit during the study. These data suggest that the initial severity of the deficit is an important predictor of outcome. None the less, stable parkinsonism can be observed in severely parkinsonian subjects despite variability in the severity of the impairment in response to MPTP treatment. Two moderately and three severely affected subjects were studied for more than six months and they appeared to show equivalent scores at six months compared with between 11 to 19 months after MPTP administration. MPTP-treatment in the vervet monkey can result in persistent long-term deficits and therefore provides an excellent phenomenological as well as neuropathological model of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1997

A high SPF sunscreen's effects on UVB-induced immunosuppression of DNCB contact hypersensitivity.

Several studies in mice of the protection afforded by sunscreens from UVB-induced suppression of contact hypersensitivity have yielded conflicting reports ranging from complete protection to no protection. Firstly, we sought to determine the effects of sunscreen and UVB on Langerhans cells; secondly we sought to determine whether the effect of preapplication of sunscreen with a sun protection factor of 30 could prevent local UVB-induced suppression of contact hypersensitivity to dinitrochlorobenzene in humans. In the first part of the study we compared a control group with a sunscreen plus UVB group and enumerated the number of Langerhans cells in each group. In the second part of the study we had four groups: a control group, a UVB group, a sunscreen group, and a sunscreen plus UVB group. Our results show that application of a sunscreen prior to UVB can prevent the decrease in number of Langerhans cells in an irradiated site. In the second part of the study, our results indicate that sunscreen, in itself, does not interfere with contact hypersensitivity, and that a high SPF sunscreen applied prior to UVB irradiation partially prevents suppression of contact hypersensitivity.

Adult↗
PubMed1997

Are patients satisfied with results from residents performing aesthetic surgery?

An 8-year survey of patient satisfaction in an academic aesthetic surgery clinic at the University of Toronto was carried out by means of a mailed questionnaire. A total of 265 questionnaires were mailed; 131 completed questionnaires (49.4 percent) were returned. Of these, 93.1 percent would recommend this clinic (88.1 percent in the first year of operation and 95.4 percent in the subsequent 7 years), and 92.9 percent would undergo the same procedure again, if required (88.3 percent in the first year and 95.0 percent in the next 7 years). The highest patient satisfaction (10 of 10) was seen in augmentation mammoplasty (average, 9.1); blepharoplasty (average, 9.0); rhytidectomy (average, 7.8), and rhinoplasty (average, 6.9). The results obtained compared favorably with recently published data of more experienced surgeons.

Adolescent↗
PubMed1997

The relationship between the sinus node and the right atrial appendage.

BACKGROUND: The developmental anatomy of the right atrium, particularly the union between its sinus venarum (sinus) and atrial portions, has not been completely settled. Invagination of the embryonic sinus into the atrium brings about electrical and structural union between these primitive chambers but results in the formation of the terminal crest, a seemingly bulky and intrusive band of muscle separating sinus from atrium. However, it is unlikely that a structure that can be found in all mammalian species is merely a functionless remnant. Structural differences between the smooth sinus and the deeply trabeculated right atrial appendage emphasize the two-part shape of the right atrium, but it is hypothesized that the sinus and atrium form a single, well-knit chamber shaped for the supply of nutrient blood to atrial conducting tissues rather than for downstream bloodflow. METHODS AND RESULTS: The morphology of the right atrium was studied grossly and microscopically in 54 adult hearts. The distribution of Thebesian sinusoids arising from the right atrial appendage was identified by ink perfusion and clearing of several additional adult and fetal hearts. The sinus node was found to be precisely co-extensive with the undercut portion of the terminal crest and with pectinate muscles lining the pyramidal portion of the right atrial appendage. Sinusoids and interpectinate spaces related to the undercut portion of the terminal crest are limited to the area of the sinus node. CONCLUSION: These findings support the hypothesis that the right atrial appendage, pectinate muscles and terminal crest evolved to supply nutrient blood to conducting myocardium of the sinus portion of the right atrium, and that this chamber, like the right ventricle, is structured as a single and completely finished unit. Interpectinate spaces and Thebesian sinusoids offer clues to the location of conducting pathways, including the sinus node.

Adolescent↗
PubMed1997

Topical treatment of psoriasis with fludarabine.

Fludarabine is not used as a topical medication for the treatment of psoriasis. In this study we evaluated the efficacy of fludarabine for this purpose. Four male patients with two bilaterally symmetrical psoriatic plaques were treated with 0.2 percent topical fludarabine in aquaphor (fludarabine site) or aquaphor alone (control site). The fludarabine and control sites were compared before and during the study on a weekly basis for three weeks by degree of redness, scaliness, and thickness on a scale of 0 to 4 (0, not apparent; 4, very apparent). The results of our study showed no significant difference between topical fludarabine and aquaphor in the treatment of psoriatic plaques.

Administration, Topical↗