Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obsessive-compulsive disorder is a chronic psychiatric illness, affecting up to 3% of the general population, to the middle of 60-th it was supposed to be untreatable. Antidepressant pharmacotherapy is one of the treatment alternatives today. We compared efficacy and safety of citalopram versus clomipramine (serotoninergic antidepressants) in 6 weeks in double blind therapy of obsessive-compulsive disorder. The second objective was to compare prolactin response to a fenfluramine challenge test before the treatment of patients and after 6 weeks of the treatment. In a sample of 14 patients we confirmed significant therapeutic response after 3 weeks of pharmacotherapy, better in obsession than in compulsion. We found low level of adverse effects in the first week of therapy--dry mouth, anxiety, nausea, somnolence, tremor, and sexual adverse events. There were no changes in the laboratory, test EEG, and ECG examinations. Fenfluramine challenge test showed statistically significant decrease of prolactin levels 1 hour after administration of fenfluramine. It was not observed after six weeks of the therapy. Statistically significant negative correlation between prolactin plasma levels at the 6th hour after administration of fenfluramine and obsession item of YBOC Scale was showed after the 3rd and 6th week of the therapy. The correlation was not observed for compulsion item YBOC Scale. Side effects observed during and after the challenge test were anxiety and nervousness and gastrointestinal problems, lasted from 1 hour to 10 hours. These preliminary result could support the idea, that obsessions and compulsions have not necessary the same biological background. The challenge paradigm appears to be a possible way to clarify the pathogenesis of OCD. Our study will continue.
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PMID:Fenfluramine challenge test in obsessive-compulsive disorder--first results. 948 83

Our experience with atypical antipsychotics in patients with PD is that their motor effects are not predictable. The multiple reports concerning clozapine's beneficial effects on tremor, dystonia, nocturnal akathisia, and dyskinesias all underscore this observation. However, the appearance of even minor degrees of parkinsonism in normal volunteers or schizophrenics should suggest that an antipsychotic will not be well-tolerated in patients with PD. The treatment of PD is probably the most stringent test of a drug's freedom from parkinsonian side effects. The data from trials in schizophrenia concerning parkinsonian effects cannot always be confidently interpreted. Virtually all subjects in these trials have been treated with typical neuroleptics until shortly before study entry. Because the parkinsonian side effects of these drugs may persist for several months, patients may still show declining levels of parkinsonism even when placed on a drug that induces it if this effect is milder than that induced by the pre-study neuroleptic. Depending on the pre-study drug used and the duration of the study, distinguishing placebo from a low-potency neuroleptic may be impossible. Furthermore, the standard measure of parkinsonism in psychiatric studies is the Simpson-Angus scale which is heavily weighted toward rigidity and may underscore bradykinesia, gait, and posture abnormalities. The prolactin response to an antipsychotic drug may turn out to be a good predictor of its freedom from parkinsonian side effects. That would fit with the data presented above of clozapine and quetiapine having less parkinsonian effects, olanzapine having more but variable effects and risperidone being poorly tolerated. With the data presented above, comprising a current review of all reports of the use of atypical antipsychotics in PD that we could locate, we can say little with certainty. The only drug with confirmed benefit without worsening parkinsonism is clozapine. Open-label trials involving over 400 patients and two multicenter, placebo-controlled, double-blind trials have demonstrated that it is effective in treating the psychosis. It improves tremor, does not worsen other motor functions to any significant extent, and is safe at low doses. Limited data provide conflicting information on both risperidone and olanzapine. Quetiapine seems to be well-tolerated with some, but definitely less, worsening of PD motor features than risperidone and olanzapine. Based on the current literature, our personal experience, and anecdotal experience of other PD specialists which we solicited, we will venture our own interpretation and recommendations. We think risperidone is poorly tolerated and should be used only as a last resort; that olanzapine is better than risperidone but will, in a majority of patients with PD, worsen motor function. We are optimistic, but not yet convinced, that quetiapine may prove to be as effective and better tolerated than clozapine. It will not require cumbersome monitoring because it does not induce a blood dyscrasia. We therefore recommend that DP be treated in the following manner. First, the anti-PD medications should be simplified and reduced as much as tolerated. We think, in general, side effects multiply more with increasing numbers of drugs than with drug dose, so that patients are more likely to tolerate a higher dose of levodopa than a lower dose of levodopa combined with other adjunctive anti-PD medications. In reducing anti-PD medications, we recommend tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. Anticholinergics are stopped first, then selegiline, dopamine agonists, amantadine, and finally COMT inhibitors, which have no psychotomimetic action of their own. Finally, levodopa is reduced. Generally, a point is reached at which the anti-PD medications cannot be reduced without jeopardizing motor function. If psychosis persists at this point, then an antipsychotic is added. (ABS
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PMID:Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease. 1075 67

Experiments with animals have shown that D2 dopamine (DA) receptors are involved in prepulse inhibition of the acoustic startle reflex (suppression of the reflex response evoked by a loud sound by prior presentation of a low-intensity stimulus). The present experiment attempted to extend this observation to man. Twelve healthy males (18-30 years), screened for normal hearing thresholds, participated in four sessions in which they received oral doses of placebo, bromocriptine 1.25 mg (a D2 receptor agonist), haloperidol 3 mg (a D2 receptor antagonist) and combined treatment with bromocriptine 1.25 mg+haloperidol 3 mg, according to a balanced double-blind protocol. Thirty-minute electromyographic recordings from the orbicularis oculi muscle of the right eye were carried out 120 min after ingestion of haloperidol and/or 90 min after ingestion of bromocriptine. Subjects received 36 40-msec sound pulses (115 dB), separated by variable intervals (mean 25 sec); in 24 of the trials the pulse was preceded by a 40-msec prepulse (75 dB in 12 trials and 85 dB in 12 trials; prepulse-pulse interval, 120 msec). The amplitude of the startle response was not significantly altered by any of the active treatments. Under the placebo condition, both 75- and 85-dB prepulses inhibited the startle response. Bromocriptine significantly attenuated this prepulse inhibition; haloperidol also produced a small but statistically significant attenuation of prepulse inhibition. Haloperidol significantly antagonized the attenuation of prepulse inhibition produced by bromocriptine. Neither drug altered self-rated alertness, physiological finger tremor, systolic or diastolic blood pressure or salivation. Bromocriptine significantly suppressed and haloperidol significantly elevated serum prolactin levels, these changes being absent when the two drugs were given in combination. The results provide evidence for the involvement of D2 DA receptors in prepulse inhibition of the startle reflex in man.
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PMID:Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic startle response in man. 1140 22

This first clinical study of olanzapine in Japanese patients with schizophrenia was conducted to investigate the efficacy and safety of olanzapine. Eighty-one patients were included in the analysis set. Mean modal dose for those patients were 9.4 +/- 3.6 mg/day. For the primary efficacy measure (Final Global Improvement Rating score), 14.8% of patients had remarkable improvement, 59.3% of patients had moderate improvement or better, and 86.4% of patients had slight improvement or better. Results from the Brief Psychiatric Rating Scale showed improvement from baseline in all clusters including positive psychotic symptoms (thought disturbance) but also against negative symptoms (anergia). The most commonly reported treatment-emergent signs and symptoms with > or =10% incidence, were insomnia, weight increase, excitement, sleepiness, and anxiety. There was a low incidence of extrapyramidal treatment-emergent signs and symptoms, and events reported were tremor (6.2%), muscle rigidity (3.7%), and akathisia (2.5%). The most commonly reported treatment-emergent laboratory changes, with > or = 20% of incidence, were prolactin elevations (24.3%) followed by increases in triglycerides (20.4%). However, mean prolactin values tended to be normalized during the study. This study result suggests that olanzapine is an "atypical" antipsychotic.
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PMID:Efficacy and safety of olanzapine, an atypical antipsychotic, in patients with schizophrenia: results of an open-label multicenter study in Japan. 1144 86

Associations between neuroleptic side effects and plasma concentrations of the drug and prolactin were investigated in 33 acutely exacerbated schizophrenic patients (16 males and 17 females) treated with a fixed dose of nemonapride (18 mg/day), a new substituted benzamide, for 3 weeks. The most frequently observed side effects during nemonapride treatment were extrapyramidal symptoms such as akathisia (69.7%), dystonia (48.5%), hypokinesia (45.5%), tremor (39.4%) and increased salivation (36.4%). There were positive correlations between prolactin response and extrapyramidal side effects (EPS) scores after 1 week (Spearman rank correlation rs=.651, P<.01), 2 weeks (rs=.567, P<.05) and 3 weeks (rs=.670, P<.01) in male patients although no significant correlations were found in female or total patients. No significant correlations were found between plasma concentrations of the drug and total or any subscale side effects scores. The present study thus suggests that the spectrum of nemonapride-induced side effects is characterized by predominant extrapyramidal symptoms, and that prolactin response as an index of dopamine blockade reflects severity of EPS at least in male patients treated with nemonapride.
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PMID:Associations between side effects of nemonapride and plasma concentrations of the drug and prolactin. 1181 5

The authors report a kindred in which GTP-CH deficiency resulted in a myoclonus-dystonia syndrome. The proband, a 17-year-old boy, presented with early-onset myoclonus and later, dystonia and bradykinesia. Blood prolactin was increased and CSF homovanillic acid, 5-hydroxyindoleacetic acid, and biopterin were all reduced. L-Dopa/carbidopa administration resulted in clinical improvement. In the paternal branch, the grandfather and three relatives had myoclonus-dystonia and resting or postural tremor of limbs. The authors found a missense mutation in the exon 6 of GCH-1 gene (K224R).
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PMID:Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome. 1239 38

A latent variable model was applied to the results of an Italian multicenter nation-wide cross-sectional study to assess the earliest health effects due to mercury (Hg) exposure caused by occupation, dental amalgams (DENTAM) and fish eating (FISH). The studied population included subjects recruited from four different geographical areas. A total number of 122 workers from chloroalkali plants and production of thermometers and neon lamps formed the occupationally exposed group, whereas 196 subjects, recruited from the same areas and not occupationally exposed to mercury, formed the control group. Neuropsychological functions were assessed with neurobehavioral testing including vigilance, motor and cognitive function, tremor measurements, and with symptoms concerning neuropsychological and mood assessment. Neuroendocrine function was examined with the measurement of prolactin (PRL) level. Parameters of immunological and renal function were also measured. The target population was characterized by the number and surface of dental amalgams and consumption of fish. In the exposed workers the average urinary mercury (U-Hg) was 10.4+/-6.9 (geometric mean 8.3, range 0.2-35.2) microg/g creatinine, whereas in the control group it was 1.9+/-2.8 (geometric mean 1.2, range 0.1-33.2) microg/g creatinine. The preliminary results indicated that finger tapping (FT) and the Branches alternate movement task (BAMT) coordination test were associated with the occupational exposure (OCCEXP). PRL was significantly decreased among the exposed workers, and inversely related to U-Hg. Among the immunological and renal parameters, cytokine serum interleuchin-8 (sIL8) and beta(2) micro globulin (beta(2)MG) were lower in the exposed group and negatively correlated to U-Hg. Small-size fish consumption was associated to a beneficial effect on symptoms reporting. No effects were observed concerning dental amalgams. After first evaluating the relationship between mercury exposure and each indicator of effect, further assessment was performed to identify the earliest effects related to mercury exposure among those who resulted in being associated in the preliminary elaboration. Two latent variables "exposure" and "effect" were identified, integrating respectively the different forms of exposure (occupational, due to dental amalgams and fish consumption) and the indicators of effects (FT, BAMT, PRL, sIL8, beta(2)MG). Confounding factors (age, alcohol, body mass index (BMI)) were considered in the same model. This further analysis showed that an inverse association of occupational exposure to mercury with PRL and BAMT, with Hg-U mediating the effect on PRL, was predominant with respect to the other form of mercury exposure, the other indicators of effect and the confounders. In conclusion, this study supports the finding of alterations of neuroendocrine secretion and motor coordination at very low occupational exposure levels of inorganic mercury, below the current ACGIH Biological Exposure Index. These changes occur at lower levels than other subtle effects on the renal function and the immunitary system. On the contrary, dental amalgams and small-size fish consumption do not seem to be associated to any adverse health effect at these exposure levels.
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PMID:Application of a latent variable model for a multicenter study on early effects due to mercury exposure. 1518 18

In order to assess early neurotoxic effects associated with relatively low levels of mercury absorbed through fish eating, two groups of 22 adult male subjects, habitual consumers of tuna fish, and 22 controls were examined using a cross-sectional field study. The assessment included neurobehavioral tests of vigilance and psychomotor function, hand tremor measurements and serum prolactin assessment. Mercury in urine (U-Hg) and serum prolactin (sPRL) were measured in all exposed subjects and controls, whereas measurements of the organic component of mercury in blood (O-Hg) were available for only 10 exposed and six controls. U-Hg was significant higher among exposed subjects (median 6.5 microg/g of creatinine, range 1.8-21.5) than controls (median 1.5 microg/g of creatinine, range 0.5-5.3). The median values of O-Hg were 41.5 microg/l among the tuna fish eaters and 2.6 microg/l in the control group. Both U-Hg and O-Hg were significantly correlated with the quantity of fish consumed per week. Significant differences in sPRL were found between exposed (12.6 ng/ml) and controls (9.1 ng/ml). Individual sPRL were significantly correlated with both U-Hg and O-Hg levels. The neurobehavioral performance of subjects who consumed tuna fish regularly was significantly worse on color word reaction time, digit symbol reaction time and finger tapping speed (FT). After considering the education level and other covariates, the multiple stepwise regression analysis indicated that O-Hg concentration was most significantly associated with individual performance on these tests, accounting for about 65% of the variance in test scores.
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PMID:Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through fish consumption. 1290 74

Five hundred and nine production workers at a manganese (Mn) smelting works comprising eight production facilities and 67 external controls were studied cross-sectionally for Mn related neuroehavioural effects. Exposure measures from personal sampling included Mn in inhalable dust as cumulative exposure indices (CEI) and average intensity (INT). Biological exposure and biological effect measures included blood (MnB), urine (MnU) manganese and serum prolactin. Endpoints included items from the Swedish nervous system questionnaire (Q16), World Health Organisation neurobehavioural core test battery (WHO NCTB), Swedish performance evaluation system (SPES), Luria-Nebraska (LN), and Danish product development (DPD) test batteries, and a brief clinical examination. Potential confounders and effect modifiers included age, educational level, alcohol and tobacco consumption, neurotoxic exposures in previous work, past medical history, previous head injury and home language. Associations were evaluated by multiple linear and logistic regression modelling. Modelling assumptions were tested. Average exposure intensity across all jobs ranged from near 0 (0.06 microg/m3) for external controls to 5.08 mg/m3 for inhalable Mn, and was greater than the ACGIH TLV for 69% of subjects. Results from the large number of tests performed resolved into three groups. Group 1 shows differences between external unexposed referents and all the exposed and/or differences between internal low exposed referents and the rest of the exposed but no further exposure-response relationships. It includes the Santa Ana, Benton and digit-span tests from the WHO NCTB; the hand tapping and endurance tapping tests from the SPES; Luria-Nebraska item 2L; questionnaire items tired, depressed, irritated, having to take notes in order to remember things, and subjects' perception that they had sex less often than normal; a test of clinical abnormality; and increased sway under two conditions (eyes open without foot insulation, eyes open with foot insulation). Group 2 shows the presence of a more substantive exposure-response relationship. It consists of only two tests: and includes the WHO digit-symbol test (although the major impact is at low exposure and therefore counterintuitive, arguably placing this test in group 3) and the LN item 1R which has a step to a poorer score at high exposure. Group 3 contains the overwhelming majority of test results (almost all the questionnaire items, almost all the DPD tests including tremor, sway and diadochokinesia, and serum prolactin) which were either null or counterintuitive (did not make sense). The CEI was the strongest predictor of test abnormalities, except for the clinical test which was more strongly associated with blood manganese. Despite a comprehensive range of endpoints, and levels of exposure ranging from environmental to industrial, this large study of Mn workers found little convincing evidence for a continuum of effects, contributing further questions to current debates about the adequacy of the current ACGIH TLV.
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PMID:The nervous system effects of occupational exposure on workers in a South African manganese smelter. 1463 83

Whether chronic cannabinoid consumption produces a dependent state comparable to that occurring with other drugs (e.g. the appearance of withdrawal signs when consumption is interrupted), and whether chronic cannabinoid consumption increases the risk of consuming other drugs of greater addictive power, are probably the two questions relating to cannabinoid addiction that provoke the most controversy. The present study was designed to further explore these two questions in laboratory animals. Firstly, we examined the effects of an acute challenge with SR141716 (an antagonist for the cannabinoid CB(1) receptor) in Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-tolerant rats. This antagonist has been reported to precipitate a cannabinoid withdrawal syndrome. Thus, the administration of SR141716 to Delta(9)-THC-tolerant rats reduced inactivity in the open-field test and enhanced responses as tremor, turning and retropulsion-these responses that were only slightly enhanced in control rats. The administration of SR141716 increased the plasma prolactin and the corticosterone concentration in controls, but these increases were much lesser in Delta(9)-THC-tolerant rats. In addition, CRF-mRNA levels in the paraventricular hypothalamic nucleus, while reduced in SR141716-treated controls, were significantly increased in Delta(9)-THC-tolerant rats. The analysis of endocannabinoids also revealed that the administration of SR141716, which was mostly inactive in control rats, was able to reverse the changes in anandamide or 2-arachidonoylglycerol concentrations found in Delta(9)-THC-tolerant rats, in the striatum, limbic forebrain, diencephalon, cerebellum and brainstem, but not in the midbrain and hippocampus. As a second objective, we evaluated whether Delta(9)-THC-tolerant rats were more vulnerable to morphine in a self-administration paradigm. The Delta(9)-THC-tolerant and control rats self-administered morphine to a similar extent, in concordance with the similar values of dopaminergic activity in limbic and motor regions. In summary, our data indicate that Delta(9)-THC-tolerant rats were not more vulnerable to the reinforcing properties of morphine. However, they responded to the blockade of CB(1) receptors by exhibiting slightly but possibly relevant differences in behavioral, endocrine and molecular parameters compared to the response in non-tolerant rats. This is indicative of the existence of a withdrawal syndrome in cannabinoid-tolerant rats that is mild compared with abstinence in opioid-dependent rats.
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PMID:Behavioral and molecular changes elicited by acute administration of SR141716 to Delta9-tetrahydrocannabinol-tolerant rats: an experimental model of cannabinoid abstinence. 1509 59


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