Biomedical subjects

K Koivisto

Publications and source records attributed to K Koivisto.

42 records · Page 3Linked to original sources

PubMed1987

Biochemical and clinical studies on epileptic patients during two phase I trials with the novel anticonvulsant taltrimide.

Taltrimide (2-phthalimidoethanesulphon-N-isopropylamide), a lipophilic derivative of taurine and a potent anticonvulsant in animal studies, was administered in daily doses of 1 and 2 g for 2 weeks with an interval of 2.5 months in 2 phase I clinical trials to 9 drug-resistant epileptic patients. Seizures and EEG were recorded, and routine laboratory studies conducted. Concentrations of antiepileptic drugs in plasma, of amino acids in urine and plasma, and contents of amino acids, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and cyclic nucleotides in the cerebrospinal fluid were determined. Although no clinical or neurophysiological effects were observed, an increase in the cerebrospinal fluid contents of HVA and cyclic nucleotides and changes in the concentrations of antiepileptic drugs and amino acids were found. The concentrations of HVA correlated with those of 5-HIAA and also with those of the main active metabolite of taltrimide. Biochemical changes due to taltrimide treatment resembled only partly those found after taurine treatment.

Adult↗

PubMedDate not supplied

Selegiline treatment and the extent of degenerative changes in brain tissue of patients with Alzheimer's disease.

BACKGROUND: A beneficial effect of selegiline (L-deprenyl) in Alzheimer's disease (AD) has been reported in several clinical studies. METHODS: The brain tissue from 17 deceased patients, members of a double-blind clinical trial to assess the potential benefit of selegiline in AD, were analysed. FINDINGS: In our study, the decrease in the Mini-Mental State Examination (MMSE) scores during the progress of the disease had been significantly influenced by selegiline treatment. Prior to death, the MMSE scores were significantly higher in those patients receiving selegiline than in those receiving placebo. However, according to our results, none of the lesions critical for AD diagnosis, such as counts of senile/neuritic plaques, neurofibrillary tangles or beta-A4 load, were influenced by the selegiline treatment. INTERPRETATION: In conclusion, according to our study, mechanisms other than neuronal degeneration seen as lesions critical for AD diagnosis are influenced by selegiline treatment, leading to the functional benefit found in AD.

Aged↗

PubMedDate not supplied

Clinical trial with an experimental taurine derivative, taltrimide, in epileptic patients.

The antiepileptic effect, effects on EEG, and tolerability of taltrimide, a new taurine derivative, were studied in this open clinical trial in 27 patients with severe epilepsy resistant to conventional drugs. After the 2-week control phase, taltrimide was given in gradually increasing doses up to 4.0 g/day--this dose used for 12 days. Taltrimide was given over 4 weeks and it was gradually withdrawn over 2 weeks. The frequency of seizures increased statistically significantly during the trial with increasing dose of taltrimide and decreased again in the withdrawal phase of the trial. Of six dropouts, one had status epilepticus, and in two patients increased number or severity of seizures necessitated withdrawal of taltrimide. There were no changes in EEG recordings or in laboratory data for safety evaluation. Taltrimide penetrated well through the blood-brain barrier, with the concentration of its main metabolite, phthalimidoethanesulphonamide, in cerebrospinal fluid, about half that in serum. The concentration of phenytoin increased statistically significantly, and there was a significant decrease in serum carbamazepine concentration during the taltrimide treatment. The anticonvulsive effect of taltrimide observed in animal experiments could not be confirmed in this study; in contrast, the seizures increased statistically significantly during taltrimide treatment. The reason for this remains obscure. The doses used, the significant drug interactions, or the patient material seemingly do not explain totally the noticed increase in seizure frequency. One explanation may be that taltrimide has proconvulsive properties in humans.

Adult↗

PubMedDate not supplied

Effects of taltrimide, an experimental taurine derivative, on photoconvulsive response in epileptic patients.

Taltrimide is a lipophilic taurine derivative with definitive anticonvulsive effects in experimental epilepsy models. In this study, taltrimide was administered for 6 days, and the effects of the treatment on photoconvulsive response in EEG in eight epileptic patients were evaluated. Discharges provoked by intermittent photic stimulation (IPS) were increased by greater than 50% in four patients after taltrimide treatment. Only one patient had reduction of sensitivity. There was only a slight change in discharges after hyperventilation and no change in spontaneous paroxysms. The effects of taltrimide on photosensitivity appear to be rather specific. The study does not reveal anticonvulsive effects of taltrimide in humans.

Animals↗

PubMedDate not supplied

Apolipoprotein E phenotype alone does not influence survival in Alzheimer's disease: a population-based longitudinal study.

Apolipoprotein E4 (ApoE4) phenotype is a known risk factor for development of Alzheimer's disease (AD). Contradictory results exist concerning the role of ApoE4 in the rate of decline and mortality in AD. Conflicting findings have also been reported about ApoE and gender interactions with respect to survival. We examined the survival of subjects with AD and non-AD controls with respect to ApoE phenotype and gender in a population-based longitudinal study. Cognitive evaluation was performed for a total of 980 subjects (then aged 69-78 years), and 48 cases with AD were identified. ApoE4 phenotype was more frequently present among subjects with AD. In the whole study population, survival was not related to the presence of AD or ApoE4 phenotype. Risk of death was increased for men compared to women, independently of the ApoE4 phenotype (HR 0.5, 95% confidence interval 0.44-0.69). In subjects with AD, the presence of ApoE4 alone did not influence survival. However, in the AD group, ApoE4-negative men had significantly increased risk of mortality compared to the risk in ApoE4-negative women (p < 0.01). We conclude that the presence of ApoE4 phenotype or AD did not influence mortality in the aged population. Once AD had become manifest, ApoE4 alone did not relate to survival. However, in subjects with AD not carrying ApoE4, men had reduced survival compared to women.

Aged↗

PubMedDate not supplied

Population-based dementia screening program in Kuopio: the effect of education, age, and sex on brief neuropsychological tests.

A neuropsychological screening battery including the Mini-Mental State Examination and four other brief cognitive tests (Russell's Adaptation of the Visual Reproduction Test, Trail Making Test, Verbal Fluency Tests on letters and category, and the Buschke Selective Reminding Test) was administered to a randomly selected population sample of 403 subjects aged 68 to 77 years to evaluate the effect of education, age, and sex on test scores. The difference in neuropsychological screening tests between various education groups (3 years or less, 4 to 6 years, 7 years or more) was statistically highly significant, even after the adjustment for the effect of age. The subscores and total scores were lowest in the minimal education group on every neuropsychological test. Education correlated more strongly than age with all neuropsychological test scores and subscores. The effect of sex on test results was seen only in some subscores of brief neuropsychological tests but not in a single item of the Mini-Mental State Examination. On the basis of our results, the effects of education, age, and sex have to be evaluated before using brief neuropsychological tests in population-based dementia screening.

Age Factors↗