Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because the symptomatic treatments for multiple sclerosis (MS) are limited, new approaches have been sought. Anatomical studies of MS lesions show a relative preservation of axons, and clinical studies suggest that some of the neurological impairment in patients with MS is physiological. Electrophysiological studies suggest that demyelination exposes axonal potassium channels that decrease action-potential duration and amplitude, hindering action-potential propagation. Potassium channel blockers, including aminopyridines, have been shown to improve nerve conduction in experimentally demyelinated nerves. Two potassium channel blockers, 4-aminopyridine (AP) and 3,4 diaminopyridine (DAP) have been tested in patients with MS. Preliminary studies of AP demonstrated benefit in many temperature-sensitive patients with MS, and improvement of function was found in a large randomized double-blind, placebo-controlled crossover trial of 3 months of oral treatment in 68 patients with MS. An open-label trial of DAP showed improvement in some deficits, and a double-blind placebo-controlled trial showed significant improvements in prospectively defined neurological deficits. A crossover comparison of the two agents suggested that AP produces more central nervous system side effects (dizziness and confusion), whereas DAP produces more peripheral side effects (paresthesias and abdominal pain). Both agents have rarely caused seizures. These studies suggest that aminopyridines may provide a new approach to the symptomatic treatment of MS.
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PMID:The current status of studies of aminopyridines in patients with multiple sclerosis. 801 70

Vigabatrin was designed to increase the levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. It does this by replacing GABA as a substrate for the action of the catabolic enzyme GABA-transaminase. As a result of this inhibition, neuronal GABA levels are elevated, resulting in enhanced endogenous GABA transmission. A number of clinical trials assessing the effect of vigabatrin in epilepsy have been completed. Vigabatrin is of proven benefit in partial seizures and secondarily generalised tonic clonic seizures, and it is licensed for use as adjunctive therapy in these conditions in several European countries. It has been shown to be effective in some epilepsy syndromes in children including West's syndrome, infantile spasms and cryptogenic partial seizures. Its effect on primary generalised tonic clonic seizures is variable, while there is considerable evidence that it has a deleterious effect on myoclonic and absence seizures. There have been a few reports of the benefits of vigabatrin in other neurological disorders including tardive dyskinesia, degenerative ataxias and GABA metabolism disorders. The adverse effects associated with vigabatrin are similar to those seen with other anticonvulsants, with a predominance of CNS effects including somnolence, fatigue, irritability, dizziness and headache. Psychiatric symptoms including depression and psychosis are seen in a small number of patients and cause the most problems. These often necessitate discontinuation of vigabatrin, which usually results in resolution of symptoms.
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PMID:A risk-benefit assessment of vigabatrin in the treatment of neurological disorders. 803 89

A multicenter, double-blind, randomized, placebo-controlled study evaluated the efficacy and safety of gabapentin (Neurontin, GBP) as add-on therapy in 272 patients with refractory partial seizures who were receiving one to two standard antiepileptic drugs (AEDs). Efficacy assessments compared the frequency of partial seizures during the 12-week treatment phase (T) and the 12-week baseline period (B). The primary analysis compared data for patients receiving GBP 900 mg/day with placebo; the GBP 1,200-mg/day group provided dose-response data. Efficacy criteria were percentage of change in seizure frequency (PCH), responder rate (percentage of patients with > or = 50% reduction in seizure frequency), and response ratio, where RRatio = (T-B)/(T + B). Median PCH was -21.8% in the 900-mg/day group and -17.8% in the 1,200-mg/day group as compared with -0.3% in the placebo group. Responder rate was 22.9% in the 900-mg/day group and 10.1% in the placebo group (p = 0.020, Fisher's exact test). Adjusted mean RRatio was -0.136 in the 900-mg/day group and -0.025 in the placebo group (p = 0.0046, analysis of variance ANOVA). Results showed slightly greater improvement for the 1,200-mg/day than for the 900-mg/day group (RRatio = -0.157, responder rate 28.0%). Adverse events (AE) occurred in 69% of patients in the 900-mg/day group and in 64% in the 1,200-mg/day group as compared with 52% in patients receiving placebo as add-on therapy. The most frequent AE among patients treated with GBP were somnolence, dizziness, and fatigue. Clinical laboratory evaluations showed no clinically important trends and no evidence of hepatic or hematopoietic effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. The International Gabapentin Study Group. 808 24

This is the 2-year interim report of results from a multicenter, open-label study evaluating the long-term efficacy and safety of gabapentin (Neurontin) as add-on therapy in patients with refractory partial seizures who had had a therapeutic response to gabapentin in a preceding 12-week double-blind trial or 12-week open-label extension. A total of 240 patients continued to receive gabapentin as add-on therapy at dosages of 600-2400 mg/day for an average of 342 days (range 10-784 days). Efficacy analyses compared seizure frequency during consecutive 12-week treatment periods with seizure frequency during the 12-week baseline. During the nine treatment periods evaluated, the percent of patients with a 50% or greater reduction in seizure frequency ranged from 35% to 71%, and the median percent change in seizure frequency ranged from -33% to -60%. At the time of data cutoff, 30% of patients had withdrawn from the study due to lack of efficacy, and 4% due to adverse events. In 225 patient-years of gabapentin treatment in this study, CNS adverse events reported by more than 10% of patients were nystagmus, somnolence, diplopia, tremor, ataxia, and dizziness. No consistent changes in clinical laboratory values were associated with gabapentin. Gabapentin as add-on therapy at dosages up to 2400 mg/day is safe during long-term treatment in patients with refractory partial seizures. Subgroup analyses of patients who remained in the study over the long term confirmed that gabapentin maintained efficacy for up to 2 years.
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PMID:The long-term safety and efficacy of gabapentin (Neurontin) as add-on therapy in drug-resistant partial epilepsy. The US Gabapentin Study Group. 808 58

The efficacy and safety of lamotrigine (LTG), a new antiepileptic drug (AED), were evaluated in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 98 patients with refractory partial seizures. Each treatment period lasted 14 weeks. Most patients were titrated to a LTG maintenance dose of 400 mg/day. Seizure frequency with LTG decreased by > or = 50%, as compared with placebo, in one fifth of patients. Overall median seizure frequency decreased by 25% with LTG as compared with placebo (p < 0.001). With LTG, the number of seizure days decreased by 18% as compared with placebo (p < 0.01), and investigator global evaluation of overall patient clinical status favored LTG by 2:1 (p = 0.013). Plasma LTG concentrations appeared to be linearly related to dosage. LTG had no clinically important effects on the plasma concentrations of concomitant AEDs. Adverse experiences were generally minor and most frequently were CNS-related (e.g., ataxia, dizziness, diplopia, headache). Most were transient and resolved without discontinuing treatment. Five patients withdrew as a result of adverse experiences while receiving LTG, including 3 patients with rash. One placebo patient was also withdrawn because of rash. The addition of twice-daily LTG to an existing AED regimen was safe, effective, and well tolerated in these medically refractory partial seizure patients.
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PMID:Lamotrigine therapy for partial seizures: a multicenter, placebo-controlled, double-blind, cross-over trial. 811 32

A 55-year-old mildly hypertensive woman died after having developed a subcortical dementia during the past 9 years, with focal neurological signs. She presented at the age of 46 years with short episodes of dizziness and diplopia, suggesting that transient ischemic attacks involved the posterior fossa structures. Over the next 8 years, she developed difficulty in walking, urinary incontinence and seizures. On examination in 1989, she was severely demented. There was tetraparesis, bilateral arm and leg spasticity with hyperreflexia and bilateral Babinski signs. She showed epilepsia partialis continua involving the eyes, left hemiface and limbs. CT showed hypodensity of the white matter and lacunes in the basal ganglia and centrum semiovale, moderate hydrocephalus with cerebellar and cortical atrophy. Clinical and radiological features were similar to those of Binswanger's disease. Similar cases had occurred in the family affecting the patient's grandfather, father and two brothers, suggesting an autosomal dominant hereditary disease. Postmortem examination disclosed a Binswanger type of leukoencephalopathy caused by a peculiar microangiopathy characterized by a slightly basophilic small arterial granular degeneration of the medial sheath associated with the presence of ballooned smooth muscle cells with clear cytoplasm. Electron microscopic study revealed degenerative changes in the parietal vessels with notable increase of basal-membrane-type material and electron-dense granular deposits. These lesions could correspond to a specific familial pathology of the small arteries of the brain. They are identical to those reported in some patients with autosomal dominant inheritance. For other patients with similar clinical features and the same familial pattern, reported as "hereditary multi-infarct dementia'' and "chronic familial vascular encephalopathy'', there are no sufficient objective pathological facts to consider that they have the same disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Small arterial granular degeneration in familial Binswanger's syndrome. 814 Aug 99

We performed a survey for taeniasis and cysticercosis among persons living in a Mexican village where Taenia solium infection in pigs was known to be enzootic. A standardized questionnaire was administered in all 577 households to obtain medical histories and information on demographic and environmental factors and on risk factors associated with transmission of infection. Serum and/or stool specimens were obtained from 1005 volunteers and examined for cysticercosis antibodies and intestinal parasites. Faecal examination of 828 participants revealed infection by Taenia sp. in 2 (0.2%). Three additional cases of taeniasis were detected in individuals who evacuated proglottids after treatment with praziquantel. Of 1005 human serum specimens, 49 (4.9%) were positive in the cysticercosis immunoblot assay. Seropositivity increased with age and reached a peak in subjects aged 46-55 years (P < 0.05). A history of seizures was significantly associated with seropositivity (P < 0.05); approximately 25% of persons with such histories were seropositive. Histories of headache, dizziness, trembling, blurred vision, and vomiting were also significantly associated with positive immunoblot assays. This study has demonstrated previously undiagnosed morbidity associated with T. solium neurocysticercosis and identified community behavioural and environmental practices that must be modified to prevent continued transmission of cysticercosis and taeniasis.
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PMID:Epidemiological investigation of Taenia solium taeniasis and cysticercosis in a rural village of Michoacan state, Mexico. 815

The new antiepileptic drug zonisamide was evaluated in a European multicenter parallel-group double-blind trial as add-on treatment for 139 patients with refractory partial epilepsy. During treatment with zonisamide complex partial seizures decreased by 27.7% compared to placebo (P < 0.05) and the median rate dropped from 12/month to 7.1/month with no changes in the placebo group (P < 0.007). During the 12-week double-blind phase a 50% reduction of all seizures was recorded in 29.9% of the patients treated with zonisamide vs. 9.4% during placebo. Complete remission was observed during treatment with zonisamide in 6.2%. The plasma concentrations of the concomitant antiepileptic drugs did not change markedly when zonisamide was added. Adverse events, mostly fatigue, somnolence, dizziness and ataxia, occurred in 59.2% of the patients compared to 27.9% during placebo. Zonisamide was withdrawn in two patients due to adverse events. Kidney stones were not observed nor any relevant clinical chemistry or hematological changes. Zonisamide is an effective antiepileptic drug for add-on treatment of refractory partial epilepsy.
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PMID:Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial. 832 80

Twelve patients with intractable partial seizures [4 receiving carbamazepine (CBZ), 4 phenytoin (PHT), and 4 both] entered a study of the tolerability of flunarizine (FNR) at specified plasma concentrations. After an 8-week baseline period, a single-dose pharmacokinetic study was performed for each patient to calculate a loading dose and maintenance dosage necessary to achieve a target plasma FNR concentration of 30 ng/ml. The first 8 patients received the loading dose (as divided doses) during a 1-week hospitalization and the maintenance dosage for the ensuing 8 weeks. These patients proceeded to treatment periods with target concentrations of 60 and then 120 ng/ml, using doses based on an assumed linear relation between dose and plasma concentration. The last 4 patients were studied only at the 120- ng/ml target level. Results indicated that this procedure successfully approximated target levels of 30 and 60 ng/ml, but observed concentrations in the last period exceeded the 120-ng/ml target level and continued to increase with time, often necessitating a dosage reduction owing to intolerability. Calculated doses for a given target concentration varied by a factor of 12. The most frequently reported adverse experiences were sedation and increased fatigue; reports of dizziness, headache, and lethargy were also common. Based on this study, a target concentration of at least 60 but < 120 ng/ml is recommended for a controlled clinical trial of the antiepileptic efficacy of FNR.
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PMID:Increasing plasma concentration tolerability study of flunarizine in comedicated epileptic patients. 840 51

This study enrolled patients with complicated urinary tract infections (UTIs) in a trial to determine the efficacy and safety of sequential therapy with intravenous fleroxacin (first 3 days) followed by oral fleroxacin, for a total course of 7-14 days, both administered at a dosage of 400 mg once a day. We enrolled 68 patients with complicated UTIs or acute pyelonephritis, 32 of whom were evaluable for bacteriologic and clinical efficacy. The pathogens isolated included Escherichia coli, 15; enterococci, 9; miscellaneous, 15. Intravenous fleroxacin was given for a mean of 3.2 days, followed by oral fleroxacin for a mean of 5.3 days. A total of 27 patients were clinically cured (84%), two improved, and three failed. A total of 26 patients were bacteriologically cured (81%), and six failed (19%). The bacteria that were not eradicated included enterococci, 4; Staphylococcus epidermidis, 1; and Pseudomonas species, 1. One enterococcal isolate became resistant to fleroxacin. Four patients were bacteremic (E. coli, 3; Proteus mirabilis, 1); the pathogen was eradicated in all cases. Two patients developed urinary enterococcal superinfections. A total of 12 patients experienced 16 adverse reactions remotely, possibly, or probably related to fleroxacin (insomnia, 3; dizziness, 2; miscellaneous, 11). One patient had a grand mal seizure after aspirating gastric contents; the seizure was thought to be only remotely related to the study drug. Fleroxacin was discontinued in two patients because of adverse effects (phlebitis at intravenous access site, 1; anxiety and insomnia, 1). Only minor and asymptomatic laboratory abnormalities were observed. All clinical and laboratory abnormalities resolved with discontinuation of the study drug. Fleroxacin is a safe and effective antibiotic for sequential intravenous and oral treatment of acute pyelonephritis and complicated UTIs. Enterococci may be problematic pathogens, as reported with other fluoroquinolones.
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PMID:A sequential study of intravenous and oral fleroxacin in the treatment of complicated urinary tract infection. 845 68


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