Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thalamic neurons are known to switch their firing from a tonic pattern during wakefulness to a bursting pattern during sleep. Several studies have described the existence of bursting activity in awake chronic pain patients and have suggested that this activity is abnormal and may be related to their pain. However, we have frequently observed bursting activity in awake non-pain patients suggesting that there may not be a causal relationship between thalamic bursting activity and chronic pain. To examine this issue more rigorously we compared the incidence and pattern of bursting activity of lateral thalamic neurons of both pain and non-pain patients in a state of wakefulness. Recordings were obtained from lateral thalamic areas of different groups of patients (n = 91) suffering from pain disorders (e.g. anaesthesia dolorosa, phantom limb pain, trigeminal neuralgia, post-stroke pain) and motor disorders (e.g. Parkinson's disease, essential tremor) during stereotactic surgical procedures for the treatment of pain and movement disorders. Burst indices (the number of bursting cells per electrode track) were computed for all the explorations in the two groups. The burst indices in the pain and non-pain groups (1.73 +/- 0.28 and 1.14 +/- 0.16, respectively) were not significantly different from each other. The bursts were analyzed to see if they fulfilled the criteria of low-threshold calcium spike (LTS)-evoked bursts characterized by (i) a shortening of the first interspike interval with an increase in the number of interspike intervals in the burst and also (ii) a progressive prolongation of successive interspike intervals. LTS-evoked bursts were identified in 27/47 (57%) bursting cells in pain patients and 15/32 (47%) cells in non-pain patients. These data demonstrate that the occurrence of bursting activity and of LTS-evoked bursts in the human thalamus is prevalent in both pain and non-pain patients. This suggests that the bursting activity of thalamic neurons in pain patients is not necessarily related to the occurrence of their pain.
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PMID:A comparison of the burst activity of lateral thalamic neurons in chronic pain and non-pain patients. 1034 18

During the period from July 1995 to June 1996 we performed transurethral resection of the prostate (TURP) on 824 patients with benign prostatic hyperplasia (BPH). Among them, 13 were dementia patients between 74 and 96 years old; they presented with urinary hesitancy in 6, retention in 4, frequency in 2 and incontinence in 1 patient. Past history included stroke in 7, hypertension in 6, pulmonary tuberculosis in 4, diabetes in 3, asthma in 2, angina pectoris in 1, Parkinson's disease in 1, pneumonia in 1, and hepatitis in 1. Careful preoperative examination revealed that they were proper candidates for TURP. They underwent TURP under spinal anesthesia. The mean operative time was 34 min, ranging from 20 to 60 min. The adenoma resected weighed 24 g on the average, ranging from 7.5 to 48 g. During surgery, although hypotension was noted in 2 patients, there was no serious morbidity. Their mental condition was well controlled with ketamine and diazepam during and after surgery. Postoperative complications included acute myocardial infarction in 1, multiple gastric ulcer in 1, and decubitus in 1. None died within 3 months after TURP, 3 died there after, and 10 patients were alive at the mean follow-up period of 26 months. Six patients reported good urination, 3 reported some improvement in urination after surgery, although requiring intermittent catheterization and 1 developed mild incontinence. In conclusion, TURP appears to provide some benefit in selected patients with dementia and should not be considered to be a contraindication for such patients.
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PMID:[Transurethral resection of the prostate for patients with dementia]. 1036 42

Deep brain stimulation by high frequency (HFS) has been developed starting in the thalamic target (Vim) from pragmatic observations and subsequently followed by other targets, such as the subthalamic nucleus (STN) and pallidum as an application of current knowledge from basic preclinical research in neuroscience. The mechanism involved by this neurosurgical approach is not completely solved. For Vim we have formed the hypothesis that HFS induces a jamming of sensory-motor loops but for the STN, from our experimental research in rats we have shown that HFS induces functional inhibition of cell activity in the target nuclei. In our patients the implantation of the stimulation electrodes was carried out stereotactically, under local anesthesia, using ventriculography, MRI, microrecordings and clinical evaluation of the effects of stimulation on rigidity. When the stimulation is turned ON in the STN area a significant decrease in rigidity was determined by the neurologists. Stimulation or even penetration of the electrode may be responsible for transient dyskinesias. The average location of the clinically efficient contact of the chronic stimulating electrodes is statistically located at 5.02 +/- 0.71 1/12 degrees of AC-PC in the AP direction, at -1.5 +/- 0.66 1/8 degrees of the height of the thalamus in the ventricle direction, with laterality at 11.98 +/- 1.12 mm in the lateral direction. The beneficial effects of STN stimulation are significant providing that the electrodes are correctly placed into the target. There is strong improvement of the symptoms of the triad in which akinesia, rigidity, and tremor are reduced on average to 41. 6, 48.6, and 27%, respectively, when compared with the previous preoperative level. From our experience, HFS of the STN could be considered the surgical therapy of choice at advanced stages of Parkinson's disease.
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PMID:Subthalamic stimulation for Parkinson's disease. 1103 79

Initially, treatment with the dopamine precursor levodopa provides substantial symptomatic relief for patients with Parkinson's disease (PD). However, as the disease progresses, side effects such as involuntary movements or psychosis may accompany the response to medication. The mechanisms underlying these actions of levodopa remain unclear. To develop methodology for longitudinal studies of the effects of PD and levodopa treatment in living nonhuman primates, we first studied the effects of an acute dose of levodopa on regional brain activity in sedated baboons using positron emission tomography. We found that levodopa significantly decreased regional cerebral blood flow (rCBF) bilaterally in putamen and right cingulate and increased rCBF in right lateral temporal cortex and bilateral frontal cortex. We then performed similar studies on a nemestrina in awake and sedated states to determine whether these responses were affected by sedation. Interestingly, the directions of the rCBF responses in the putamen and temporal cortex were reversed depending on the presence or absence of sedation. Specifically, responses were decreased in sedated animals, but increased dose-dependently in the awake nemestrina. These findings have important implications for the interpretation of studies that use anesthesia. The responses in the awake nemestrina were most similar to those reported in humans and thus may be the most useful model system. Future imaging studies using selective dopaminergic agents in awake animals may permit the identification of relatively specific agonist-mediated pathways and may help separate the mechanisms that mediate levodopa's benefit from those that produce its unwanted side effects.
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PMID:Dopa-induced blood flow responses in nonhuman primates. 1108 99

In this unblinded, randomized controlled trial, we compared supraorbital and greater occipital nerve blocks with subcutaneous infiltration for anesthesia during the placement of a stereotactic head-frame. Twenty consecutive patients scheduled for functional surgery to treat Parkinson's disease were studied. Each patient received supraorbital and greater occipital nerve blocks on one side of the head and subcutaneous infiltration on the other, thereby acting as their own control. Pain was assessed by visual analog scale pain scores (scale: 0-100) for both local anesthetic injection and stereotactic pin placement. Supplementary subcutaneous infiltration was also recorded. Results are presented as mean +/- SD. Nerve blocks were significantly less painful than subcutaneous infiltration of local anesthetic at both the frontal (34 +/- 24 vs 49 +/- 25) and occipital (34 +/- 21 vs 49 +/- 23) sites. Neither technique was superior in preventing pain associated with pin placement, at either the frontal site (48 +/- 27 vs 46 +/- 24) or occipital site (33 +/- 27 vs 32 +/- 24). Supraorbital nerve blocks required significantly more supplementation than either greater occipital nerve blocks or subcutaneous infiltration. Visual analog scale pain scores were greater at local anesthetic injection and pin placement than at any subsequent time. We conclude that supraorbital and greater occipital nerve blocks are an alternative to subcutaneous infiltration for the placement of a stereotactic frame.
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PMID:Nerve blocks versus subcutaneous infiltration for stereotactic frame placement. 1115 45

Recent studies provide evidence that phospholipase A2 (PLA2) may play a role in the development of experimental parkinsonism. In this investigation an attempt was made to determine a possible protective effect of quinacrine (QNC), a PLA2 inhibitor on MPTP as well as 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rodents. For MPTP studies, adult male mice (C57 BL) were treated with MPTP (30 mg/kg, i.p.) daily for 5 days. QNC was injected i.p. in the doses of 0, 10, 30 and 60 mg/kg daily 30 min before MPTP in four different groups. Two other groups of mice received either vehicle (control) or a high dose of QNC (60 mg/kg). Two hours after the last injection of MPTP, striata were collected for the analysis of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and glutathione (GSH). For the 6-OHDA study, male Wistar rats were infused with 6-OHDA (60 microg) in the right striatum under chloral hydrate anesthesia. The rats in different groups were treated with 0, 5, 15 and 30 mg/kg QNC (i.p.) for 4 days, while first injection was given 30 min before 6-OHDA. On day 5, rats were sacrificed and striata were stored at -80 degrees C. Administration of MPTP or 6-OHDA significantly reduced striatal DA, which was significantly attenuated by QNC. Concomitant treatment with QNC also protected animals against MPTP or 6-OHDA-induced depletion of striatal GSH. Our findings clearly suggest the role of PLA2 in MPTP and 6-OHDA induced neurotoxicity and oxidative stress. However, further studies are warranted to explore the therapeutic potential of PLA2 inhibitors for the treatment of Parkinson's disease.
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PMID:Protective effect of quinacrine on striatal dopamine levels in 6-OHDA and MPTP models of Parkinsonism in rodents. 1122 16

The subthalamic nucleus-globus pallidus network plays a central role in basal ganglia function and dysfunction. To determine whether the relationship between activity in this network and the principal afferent of the basal ganglia, the cortex, is altered in a model of Parkinson's disease, we recorded unit activity in the subthalamic nucleus-globus pallidus network together with cortical electroencephalogram in control and 6-hydroxydopamine-lesioned rats under urethane anaesthesia. Subthalamic nucleus neurones in control and 6-hydroxydopamine-lesioned animals exhibited low-frequency oscillatory activity, which was tightly correlated with cortical slow-wave activity (approximately 1 Hz). The principal effect of dopamine depletion was that subthalamic nucleus neurones discharged more intensely (233% of control) and globus pallidus neurones developed low-frequency oscillatory firing patterns, without changes in mean firing rate. Ipsilateral cortical ablation largely abolished low-frequency oscillatory activity in the subthalamic nucleus and globus pallidus. These data suggest that abnormal low-frequency oscillatory activity in the subthalamic nucleus-globus pallidus network in the dopamine-depleted state is generated by the inappropriate processing of rhythmic cortical input. A component (15-20%) of the network still oscillated following cortical ablation in 6-hydroxydopamine-lesioned animals, implying that intrinsic properties may also pattern activity when dopamine levels are reduced. The response of the network to global activation was altered by 6-hydroxydopamine lesions. Subthalamic nucleus neurones were excited to a greater extent than in control animals and the majority of globus pallidus neurones were inhibited, in contrast to the excitation elicited in control animals. Inhibitory responses of globus pallidus neurones were abolished by cortical ablation, suggesting that the indirect pathway is augmented abnormally during activation of the dopamine-depleted brain. Taken together, these results demonstrate that both the rate and pattern of activity of subthalamic nucleus and globus pallidus neurones are altered profoundly by chronic dopamine depletion. Furthermore, the relative contribution of rate and pattern to aberrant information coding is intimately related to the state of activation of the cerebral cortex.
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PMID:Dopamine regulates the impact of the cerebral cortex on the subthalamic nucleus-globus pallidus network. 1156 3

Neuronal nicotinic acetylcholine receptors (nAchRs) are widely expressed in the central and autonomic nervous systems and have subunit compositions with biophysical and pharmacological properties distinct from those of the receptors at the neuromuscular junction. They are thought to modulate synaptic transmission in the central nervous system (CNS) mainly by regulating the release of neurotransmitters. Although roles of neuronal nAchRs in the CNS are poorly understood, these receptors are involved in cognitive performance, nociception and psychoneurological disorders such as Alzheimer's and Parkinson disease. It is known that both central and peripheral neuronal nAchRs are sensitive to various types of anesthetics. Among those, barbiturates, ketamine, volatile and gaseous anesthetics depress neuronal nAchRs at or below clinical concentrations. Inhibition of neuronal nAchRs by barbiturates is unlikely to contribute to the anesthetic action of barbiturates, since this effect does not correlate with the anesthetic potencies of barbiturate stereoisomers. Relevance of inhibition of these receptors is controversial for anesthetic effects of other anesthetics, because conflicting results have been obtained from comparison of this effect with anesthetic actions of stereoisomers or structurally related compounds. However, it is possible that inhibition of central nAchRs contributes to secondary effects attributed to anesthesia such as impairment in memory and cognitive performance.
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PMID:[Effects of general anesthetics on neuronal nicotinic acetylcholine receptors and their roles in the mechanism of anesthesia]. 1171 38

Aretrospective hospital-based case-control study was performed with the aim to evaluate the association between exposure to anesthesia and Alzheimer's disease (AD). A total of 115 AD patients, 230 Parkinson's disease (PD) patients and 230 patients with non-degenerative neurological disease were studied. Each AD case was matched for sex, age (+/-3 years) and geographic area of residence with four controls (2 PD patients and 2 with other neurological disease). Information about exposure to general anesthesia and other variables was gathered through hospital records. No associations were found between the risk of AD and the exposure to anesthesia in the 1 and 5 years preceding disease onset, nor between the risk of AD and the number of surgical operations. A significant difference was observed between the mean age of AD patients and controls undergoing surgical procedures. The present study reveals a lack of association between exposure to general anesthesia and AD. Prospective epidemiological studies are needed in order to investigate levels of exposure to anesthesia, as well as any possible relationships between anesthetic exposure and genetic factors (e. g. APOEepsilon4 genotype).
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PMID:A case-control study on Alzheimer's disease and exposure to anesthesia. 1211 15

THALAMUS: The human thalamus is a nuclear complex located in the diencephalon and comprising of four parts (the hypothalamus, the epythalamus, the ventral thalamus, and the dorsal thalamus). The thalamus is a relay centre subserving both sensory and motor mechanisms. Thalamic nuclei (50-60 nuclei) project to one or a few well-defined cortical areas. Multiple cortical areas receive afferents from a single thalamic nucleus and send back information to different thalamic nuclei. The corticofugal projection provides positive feedback to the "correct" input, while at the same time suppressing irrelevant information. Topographical organisation of the thalamic afferents and efferents is contralateral, and the lateralisation of the thalamic functions affects both sensory and motoric aspects. Symptoms of lesions located in the thalamus are closely related to the function of the areas involved. An infarction or haemorrhage thalamic lesion can develop somatosensory disturbances and/or central pain in the opposite hemibody, analgesic or purely algesic thalamic syndrome characterised by contralateral anaesthesia (or hypaesthesia), contralateral weakness, ataxia and, often, persistent spontaneous pain. BASAL GANGLIA: Basal ganglia form a major centre in the complex extrapyramidal motor system, as opposed to the pyramidal motor system (corticobulbar and corticospinal pathways). Basal ganglia are involved in many neuronal pathways having emotional, motivational, associative and cognitive functions as well. The striatum (caudate nucleus, putamen and nucleus accumbens) receive inputs from all cortical areas and, throughout the thalamus, project principally to frontal lobe areas (prefrontal, premotor and supplementary motor areas) which are concerned with motor planning. These circuits: (i) have an important regulatory influence on cortex, providing information for both automatic and voluntary motor responses to the pyramidal system; (ii) play a role in predicting future events, reinforcing wanted behaviour and suppressing unwanted behaviour, and (iii) are involved in shifting attentional sets and in both high-order processes of movement initiation and spatial working memory. Basal ganglia-thalamo-cortical circuits maintain somatotopic organisation of movement-related neurons throughout the circuit. These circuits reveal functional subdivisions of the oculomotor, prefrontal and cingulate circuits, which play an important role in attention, learning and potentiating behaviour-guiding rules. Involvement of the basal ganglia is related to involuntary and stereotyped movements or paucity of movements without involvement of voluntary motor functions, as in Parkinson's disease, Wilson's disease, progressive supranuclear palsy or Huntington's disease. The symptoms differ with the location of the lesion. The commonest disturbances in basal ganglia lesions are abulia (apathy with loss of initiative and of spontaneous thought and emotional responses) and dystonia, which become manifest as behavioural and motor disturbances, respectively.
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PMID:Functional anatomy of thalamus and basal ganglia. 1219 99


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