Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a multicenter placebo-controlled study, the safety, side effects, and patient acceptance of alprazolam for the treatment of panic disorder and agoraphobia were examined. A total of 525 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder were randomly assigned to receive alprazolam or placebo, which they took for eight weeks. The mean daily dose at the end of the study was 5.7 mg of alprazolam or 7.5 capsules of placebo daily. Potentially serious reactions to alprazolam occurred in ten of 263 subjects who received the drug. These included acute intoxication (three), hepatitis (two), mania (two), amnesia (one), aggressive behavior (one), and depression (one). Treatment-related side effects that were worse in patients taking alprazolam than in those taking placebo included sedation, fatigue, ataxia, slurred speech, and amnesia. Sedation was the most frequent but tended to subside with dose reduction or continued administration of the drug. Patient acceptance of alprazolam, as measured by the rate of completion for study participants, was high. Eighty-four percent of patients receiving active drug completed the study compared with 50% receiving placebo.
Arch Gen Psychiatry 1988 May
PMID:Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. II. Patient acceptance, side effects, and safety. 335 44

This study evaluates multiple aspects of the reaction to two doses of ethanol (0.75 and 1.1 mL/kg) in 30 sons of alcoholic fathers and 30 matched controls with no known alcoholic relatives. Based on results of prior research, the evaluations included the postethanol changes in subjective feelings, levels of body sway or static ataxia, and plasma levels of prolactin and cortisol. A stepwise discriminant function analysis on the sample of 60 men revealed that four items (maximum terrible subjective feelings after high dose, cortisol values at two time points after high dose, and prolactin results after low dose) combined to correctly identify 83% of the controls and 70% of the sons of alcoholics. This included approximately 40% of each group whose discriminant scores were +1 or -1 and who were considered to be solidly classified. These results were relatively robust on a jackknife validation procedure. Results of a search for independent factors in the cluster of test scores after ethanol using a principal components analysis were consistent with the discriminant analysis, indicating the possibility of three overlapping domains of the ethanol response, including subjective feelings after the high-dose ethanol challenge (explaining 46% of the variance), hormonal changes after high-dose ethanol along with body sway items (14% of variance), and prolactin changes after low-dose ethanol (9% of variance). There were few background differences between men who had been properly and improperly classified.
Arch Gen Psychiatry 1988 Mar
PMID:A simultaneous evaluation of multiple markers of ethanol/placebo challenges in sons of alcoholics and controls. 342 53

This study measures the amount of body sway or static ataxia in 34 drinking but nonalcoholic men 21 to 25 years of age who have an alcoholic first-degree relative (the family-history-positive, or FHP, group). Results are compared with 34 control subjects matched pairwise on demographic characteristics and drinking histories, but who have no known alcoholic close relatives (the family-history-negative, or FHN, group). Each man was tested on three occasions where he drank either placebo, or 0.75 mL/kg or 1.1 mL/kg of ethanol; the subjects were repeatedly tested during the subsequent four hours. At the baseline of each of the three test sessions, the level of body sway for the two family-history groups was virtually identical. However, following the 0.75-mL/kg dose, the increase in body sway was significantly less for the FHP than for FHN group, with similar but less dramatic group differences noted following the ingestion of 1.1 mL/kg of ethanol. These results are consistent with the significantly less intense subjective feelings of intoxication after drinking for the FHP men, and also parallel findings of less intense ethanol-related changes in biologic and cognitive test scores. A decreased intensity of reaction to ethanol should be explored further as a possible genetic trait marker of a predisposition toward alcoholism.
Arch Gen Psychiatry 1985 Apr
PMID:Ethanol-induced changes in body sway in men at high alcoholism risk. 397 55

To determine whether the aetiological agent of bovine spongiform encephalopathy (BSE) is pathogenic for mink, standard dark mink were inoculated with coded homogenates of bovine brain from the U.K. Two homogenates were from cows affected with BSE. The third was from a cow that came from a farm with no history of having had BSE or having been fed ruminant-derived, rendered by-products, the proposed vehicle for introduction of the BSE agent. Each homogenate was inoculated intracerebrally into separate groups of mink and a pool of the three was fed to a fourth group. Signs of neurological disease appeared in mink an average of 12 months after intracerebral inoculation and 15 months after feeding. Decreased appetite, lethargy and mild to moderate pelvic limb ataxia were the predominant clinical signs, quite unlike the classic clinical picture of transmissible mink encephalopathy (TME). Microscopic changes in brain sections of most affected mink were those of a scrapie-like spongiform encephalopathy. Vacuolar change in grey matter neuropil was accompanied by prominent astrocytosis. Varying greatly in severity from one mink to another, the degenerative changes occurred in the cerebral cortex, dorsolateral gyri of the frontal lobe, corpus striatum, diencephalon and brainstem. Although resembling TME, the encephalopathy was distinguishable from it by less extensive changes in the cerebral cortex, by more severe changes in the caudal brainstem and by sparing of the hippocampus. The results of this study extend the experimental host range of the BSE agent and demonstrate for the first time the experimental oral infection of mink with a transmissible spongiform encephalopathy agent from a naturally infected ruminant species.
J Gen Virol 1994 Sep
PMID:Experimental infection of mink with bovine spongiform encephalopathy. 807 14

To investigate whether nitric oxide (NO) plays a role in degenerative neurologic disease (DND), we measured nitrite, nitrate and cyclic GMP in cerebrospinal fluid (CSF) samples from patients with Parkinson's disease (PD), spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis (ALS). We found no significant change in CSF nitrite, nitrate or cyclic GMP in patients with any DND compared with control values. These results suggest that NO production is preserved in PD, SCA and ALS.
J Neural Transm Gen Sect 1995
PMID:Nitrite, nitrate and cGMP in the cerebrospinal fluid in degenerative neurologic diseases. 874 72

Locomotor activity (tremor, ataxia, immobility, epilepsy, and paralysis) in the taiep rat, which suffers from a myelin deficient disorder, has not been previously documented. This study used walking track analysis of footprints to analyze locomotor activity in the taiep rat in comparison to normal, age-matched controls. The results confirmed differences between normal and taiep rats in terms of stride length, step length, and stride width. In addition, we found significant interactions between age and condition for stride and step length. The results suggest that locomotor analysis is a sensitive indicator of myelin deficiency. The results are discussed in terms of the underlying myelin deficiency and possible treatment regimens.
J Gen Psychol 2000 Oct
PMID:Locomotor analysis of the taiep rat. 1111 3

Late onset ataxia reported in three independently derived PrP null lines of mice has been attributed to the overexpression of the doppel protein in the CNS of these mice rather than to the loss of PrP. The central role of PrP in the transmissible spongiform encephalopathies (TSEs), the proximity of the gene which encodes doppel (Prnd) to the PrP gene (Prnp) and the structural similarity shared by PrP and doppel have led to the proposition that ataxia which develops during TSE disease could, in part, be due to doppel. In order to address this hypothesis, we have crossed our two inbred lines of PrP null mice, which either express (RCM) or do not express (NPU) the Prnd gene in the CNS, with mice expressing two Prnp(a[108F189V]) alleles of the PrP gene. We have found that the TSE infection does not influence the level of expression of Prnd in the CNS at the terminal stages of disease. Moreover, we have demonstrated that the level of expression of Prnd in the CNS has no influence on the incubation period, vacuolar pathology nor amount or distribution of PrP(Sc) deposition in the brains of the TSE-infected mice. Doppel has therefore no apparent influence on the outcome of TSE disease in transgenic mice, suggesting it is unlikely to be involved in the naturally occurring TSE diseases in other species.
J Gen Virol 2002 Mar
PMID:Expression of doppel in the CNS of mice does not modulate transmissible spongiform encephalopathy disease. 1184 65

The taiep (tremor, ataxia, immobility, epilepsy, and paralysis) myelin mutant displays a number of locomotor deficits. Taiep rat gait is characterized by shorter stride and step lengths as well as by larger stride widths. Thirty-day-old taiep mutants were placed under a regimen of daily hormone injections for 60 days. Animals in Condition 1 received melatonin, those in Condition 2 received pregnenolone sulfate, and those in a third control condition received injections of saline. Following the injections, each taiep mutant's gait was analyzed. The animals that received melatonin and pregnenolone displayed significantly larger stride and step lengths than did the controls. In addition, the animals that received hormones displayed shorter stride widths than did the controls. These experimental effects are consistent with a normalization of gait. Possible cellular mechanisms of this behavioral effect are discussed.
J Gen Psychol 2002 Jul
PMID:Behavioral effects of chronic melatonin and pregnenolone injections in a myelin mutant rat (taiep). 1222 8

Poliovirus and enterovirus 71 (EV71) are both neurotropic enteroviruses that cause serious neurological diseases, such as poliomyelitis and encephalitis. The neurovirulence of EV71 in cynomolgus monkeys was demonstrated previously by intraspinal inoculation. In this study, an improved simian model of EV71 infection was established by using intravenous inoculation, which revealed clinical and neuropathological similarities between this model and human cases of encephalitis. Experimental EV71 infection induced direct neurological manifestations, such as tremor, ataxia and brain oedema, but not non-neurological complications, such as pulmonary oedema and cardiac failure. Using this model of EV71 infection, the neurotropic characteristics of the prototype strains of EV71 and poliovirus type 1 (PV1) were compared. Three monkeys were inoculated intravenously with 10(5.5) TCID50 EV71 and all developed neurological disease signs within 4-6 days of inoculation. However, after inoculation with 10(5.5) TCID50 PV1 strain OM1 (PV1-OM1), the major manifestation was flaccid paralysis, starting from the lower limbs 6-9 days post-inoculation. Histopathological and virological analyses of moribund monkeys revealed that disseminated EV71 infection was characterized by severe panencephalitis involving both the pyramidal and extrapyramidal systems. In contrast, the lesions induced by PV1-OM1 were mainly restricted to the pyramidal tract, particularly the spinal motor neurons, thalamus and motor cortex. In conclusion, neuropathological involvement in this model correlated well with the apparent differences in neurological disease induced by EV71 and PV1-OM1. Thus, intravenous inoculation with EV71 is an excellent model to study the neuropathology of EV71 and to evaluate candidate vaccines and potential antiviral agents.
J Gen Virol 2004 Oct
PMID:Differential localization of neurons susceptible to enterovirus 71 and poliovirus type 1 in the central nervous system of cynomolgus monkeys after intravenous inoculation. 1544 61

There is growing evidence from both uncontrolled and controlled clinical studies that lamotrigine (LTG) significantly augments clozapine (CLZ) in the treatment of refractory schizophrenia (RS) [Dursun, S.M., McIntosh, D., Milliken, H., 1999. Clozapine plus lamotrigine in treatment-resistant schizophrenia. Arch. Gen. Psychiatry 56, 950; Dursun, S.M., Deakin, J.F.W., 2001. Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. J. Psychopharmacol. 15, 297-301; Tiihonen, J., Hallikainen, T., Ryynanen, O.P., Repo-Tiihonen, E., Kotilinen, I., Eronen, M., Toivonen, P., Wahlbeck, K., Putkonen, A., 2003. Lamotrigine in treatment-resistant schizophrenia; a randomized placebo-controlled cross over trial. Biol. Psychiatry 54, 1241-1248; Kremer, I., Vass, A., Gorelik, I., Bar, G., Blanaru, M., Javitt, D.C., Heresco-Levy, U., 2004. Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia. Biol. Psychiatry. 56, 441-446]. However, the precise mechanism of action of this synergistic augmentation between clozapine and lamotrigine remains unclear. Therefore, the goal of this research is to explore the mechanism of action of this synergistic interaction between CLZ and LTG, utilizing a pharmacological animal model of schizophrenia by using phencyclidine (PCP). The effects of CLZ plus LTG were assessed by measuring PCP-induced hyper-locomotion and stereotyped behaviours in rats. Adult male rats (250-300 g) were pre-treated via intra-peritoneal (i.p.) injection with vehicle or drug 30 min before a PCP (5 mg/kg) or saline challenge. The behaviours were recorded and analysed for a 90-min period using the Etho Vision-computer based system. PCP produced hyper-locomotion, which was maximal at 30 min. LTG (10 mg/kg) significantly increased hyperlocomotion induced with PCP. However, a combination treatment of CLZ (5 mg/kg) plus LTG (10 mg/kg) significantly blocked the potentiation of PCP-induced hyper-locomotion observed with LTG (10 mg/kg) alone. Furthermore, the PCP-induced locomotion in the combination CLZ plus LTG-treated rats was significantly decreased when compared to vehicle. Therefore, LTG at doses that do not induce ataxia enhanced PCP-induced hyper-locomotion in rats, whereas the combination of LTG and CLZ significantly decreased PCP-induced hyper-locomotion consistent with clinical data.
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PMID:Effects of clozapine plus lamotrigine on phencyclidine-induced hyperactivity. 1630 24


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