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E Säkö

Publications and source records attributed to E Säkö.

16 recordsLinked to original sources
PubMed2006

Testing of variants of the MTHFR and ESR1 genes in 1798 Finnish individuals fails to confirm the association with migraine with aura.

Among the few independently replicated genetic associations in migraine are polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and oestrogen receptor (ESR1) genes. We studied the contribution of these genes to migraine susceptibility by genotyping six MTHFR and 26 ESR1 polymorphisms in 898 unrelated migraine with aura (MA) patients and in 900 unrelated healthy controls. There were no differences in the genotype distributions of the previously migraine-associated SNPs C677T (MTHFR) and G2014A (ESR1) between cases and controls (P-values 0.83 and 0.55, respectively). Thus, we were not able to replicate the previous findings, although our study had considerable power. However, five of the ESR1 SNPs (rs6557170, rs2347867, rs6557171, rs4870062 and rs1801132) that were in strong linkage disequilibrium were nominally associated with MA (uncorrected P-values 0.007-0.034). These results did not, however, remain significant after taking multiple testing into account. Thus it seems unlikely that the studied genes are involved in migraine susceptibility, at least in this sample.

Estrogen Receptor alpha↗
PubMed2000

Modified-release formulation of tizanidine in chronic tension-type headache.

The efficacy of the modified-release formulation of tizanidine (Sirdalud) was compared with placebo in a randomized, double-blind, parallel-group study of 138 women and 47 men, aged 18 to 79 years, with a history of chronic tension-type headache (IHS categories 2.2 and 2.3). The treatment period was 6 weeks preceded by a 2-week prerandomization period. The patients were randomly assigned to receive 6-mg Sirdalud, 12-mg Sirdalud MR, or placebo. The study medication was taken once per day, orally in the evening. Efficacy was measured by visual analog scale, the number of headache-free days, the daily duration of headache, and the use of paracetamol. The primary end point was the severity of daily headache derived from visual analog scale scores covering the last 2 treatment weeks. One hundred sixty patients (56 in the 6-mg group, 49 in the 12-mg group, and 55 in the placebo group) completed the study. The severity of the headache decreased similarly in the treatment groups and the placebo group. The visual analog scale values decreased from the prerandomization values by 53% in the 6-mg group, 48% in the 12-mg group, and 52% in the placebo group. The modified-release formulation of tizanidine in doses up to 12 mg taken in the evening is not superior to placebo in the treatment of chronic tension-type headache. The placebo effect was unexpectedly strong in the present study, supporting the view that psychophysiological mechanisms are of considerable importance in sustaining chronic tension-type headache.

Adrenergic alpha-Agonists↗
PubMed1993

Brain methionine- and leucine-enkephalin receptors in patients with dementia.

Brain [3H]Met- and [3H]Leu-enkephalin binding was studied in patients with Alzheimer's disease (AD) and vascular dementia (VD), and in age-matched controls. Brain areas investigated were the internal and external globus pallidus, amygdala, hippocampus and temporal cortex. In AD, the binding of both enkephalins decreased in all brain areas examined, except in the external globus pallidus for both enkephalins and in the internal globus pallidus for leucine-enkephalin. Scatchard analysis of amygdaloid samples showed a decrease in the number of receptors (Bmax) without any change in their affinity (Kd). In patients with VD, no significant changes in enkephalin binding were seen. Thus, in AD, enkephalin binding (mainly reflecting delta opioid receptor subtype) is decreased, especially in limbic areas.

Aged↗
PubMed1993

Decrease in human striatal dopamine D2 receptor density with age: a PET study with [11C]raclopride.

The effect of age on human striatal dopamine D2 receptors was investigated with positron emission tomography (PET) using [11C]raclopride as a radioligand. Twenty-one healthy volunteers aged from 20 to 81 years were studied. An equilibrium method was applied and two separate PET scans with different specific activities of [11C]raclopride were performed. The maximal number of receptors (Bmax) and their dissociation constant (Kd) were calculated using Scatchard analysis. There was an age-dependent decline in the Bmax (r = -0.49; p = 0.02) of striatal D2 receptors while the Kd remained unchanged. The results show that there is an age-related loss of striatal D2 receptors, which, together with other changes in the brain nigrostriatal dopaminergic system, may contribute to extrapyramidal symptoms associated with aging.

Adult↗
PubMed1990

The effects of beta-adrenoceptor antagonists and levomepromazine on the metabolic ratio of debrisoquine.

The in vivo inhibitory effect of five beta-adrenoceptor antagonists and levomepromazine on debrisoquine metabolism was assessed in 37 subjects. The debrisoquine phenotyping test was performed before and after 7 days' treatment with oxprenolol (40 mg three times daily), propranolol (20 mg three times daily), timolol (10 mg twice daily), pindolol (5 mg twice daily), metoprolol (50 mg twice daily) or levomepromazine (10 mg daily), each of which was given to six-seven subjects. No clear change in the urinary metabolic ratio of debrisoquine/4-OH-debrisoquine (MR) was seen with any of the single beta-adrenoceptor antagonist treatments, but the MR value increased significantly when all beta-adrenoceptor blocker treatments were considered together. Debrisoquine metabolism was clearly impaired after levomepromazine 10 mg daily for 7 days; the mean MR increased from 1.24 +/- 1.6 to 4.70 +/- 5.23 (P = 0.018) and the excretion of 4-hydroxydebrisoquine decreased from 0.92 +/- 0.46 mg to 0.31 +/- 0.19 mg (P = 0.043). Thus, levomepromazine changes MRs towards those characteristic of phenotypically poor metabolizers, but beta-adrenoceptor antagonists at the doses examined have only a marginal effect.

Adrenergic beta-Antagonists↗
PubMed1989

Neuronal loss in the substantia nigra in patients with Alzheimer's disease and Parkinson's disease in relation to extrapyramidal symptoms and dementia.

Regional neuronal loss in the substantia nigra (SN) was studied in relation to extrapyramidal symptoms and dementia in 27 patients with Alzheimer's disease (AD), 12 patients with idiopathic Parkinson's disease (PD) and 18 controls. Four areas of the right SN were investigated at the level of the caudal red nucleus. In AD the number of neurons were reduced to 97%, 79%, 83% and 78% of the control values from the medial to lateral SN respectively. The number of lateral neurons showed a negative correlation with the severity of rigidity and hypokinesia. The degree of dementia did not have a significant correlation with nigral neuronal counts. In PD, the number of neurons was markedly reduced in all parts of the SN, most pronouncedly in the lateral part. The number of lateral neurons showed a negative correlation with the severity of rigidity and hypokinesia, whereas tremor had a positive correlation. The degree of dementia of the patients had a negative correlation with the number of medial neurons, suggesting that degeneration of the nigrostriatal neurons may contribute as a subcortical component to dementia in PD patients.

Aged↗
PubMed1988

A comparison of brain choline acetyltransferase activity in Alzheimer's disease, multi-infarct dementia, and combined dementia.

Brain choline acetyltransferase (ChAT) activity was determined in 43 patients with Alzheimer's disease (AD), 14 with multi-infarct dementia (MID), and 15 with combined dementia (CD) and in 53 age-matched controls. The activity of ChAT declined in the hippocampus, temporal and frontal cortex in patients with AD and CD compared to the controls. In the AD group the reduced activity of ChAT in all brain areas was associated with a greater number of cortical neurofibrillary tangles. The degree of dementia had a negative correlation with the activity of ChAT in the frontal cortex in both AD and CD patients. The activity of ChAT in the temporal cortex of CD patients was negatively associated with the cortical tangle counts. In contrast, the activity of ChAT and MID patients was not essentially different from that of the controls. Neither did the various clinical and neuropathological variables show any significant correlation with ChAT activity in MID patients. Thus, in this study the reduction in the activity of ChAT seems to be associated with Alzheimer-type pathology but not with dementia due to vascular changes.

Aged↗
PubMed1987

Alzheimer's disease: neuropathological correlates of cognitive and motor disorders.

Correlations between clinical symptoms and changes in brain neuropathology were investigated in 34 patients with Alzheimer's disease, who were compared with 17 non-demented, age-matched controls. The patients were originally found in a community survey of dementia and were followed up prospectively until death. A highly significant correlation emerged between the severity of dementia and the numbers of plaques and tangles in the material as a whole, but no essential difference was found between severely and less severely demented patients. Low brain weight correlated highly with many clinical symptoms and signs and the severity of dementia. A multiple regression model consisting of plaques and tangles in amygdala, gyrus frontalis medius, gyrus angularis, and gyrus temporalis medius, plaques of gyrus rectus, tangles of the hippocampus, gyrus precentralis and gyrus cinguli together with brain weight, emerged to link dementia to neuropathological changes at the level of maximum significance. Dyskinetic movements were associated with damage of several brain areas, implying a multiple etiology.

Alzheimer Disease↗
PubMed1986

Brain dopamine D-2 receptors in senile dementia.

Brain dopamine D-2 receptors were analysed in the caudate nucleus, putamen and nucleus accumbens in 49 patients with different types of neuropathologically verified dementia and in 39 controls by the binding of 3H-spiroperidol. The binding was significantly decreased in all brain areas in patients with Alzheimer's disease (AD), while the changes in patients with multi-infarct dementia (MID) or combined dementia (CD) were non-significant. According to a Scatchard analysis, this decrease in binding was due to the reduced number of receptors. On the other hand, the binding of 3H-spiroperidol was significantly increased in those patients who had received neuroleptic drugs. Significant correlations between 3H-spiroperidol binding and neuropathological changes were seen only in AD patients in the nucleus accumbens. The nucleus accumbens was also the only brain area in which there was a significant correlation between dopamine D-2 and the number of muscarinic receptors in AD patients. The findings of this study on dopamine D-2 receptors suggest the involvement of the nigrostriatal dopaminergic system in AD but not in the other two major types of dementia.

Aged↗
PubMed1986

Brain dopamine D-1 receptors in senile dementia.

Brain dopamine D-1 binding sites were studied by using [3H]flupenthixol in 4 brain regions of 44 senile patients with neuropathologically verified organic dementia and 28 age-matched controls. The D-1 binding sites were decreased in the substantia nigra and nucleus accumbens in patients with Alzheimer's disease, while no change was found in multi-infarct or combined dementia. The striatal D-1 binding sites were unchanged in all groups of patients. Only a few correlations between various clinical and post-mortem variables and the [3H]flupenthixol binding of the dementia patients were found. The findings of this study indicate that there is reduction of brain D-1 binding sites in patients with Alzheimer's disease.

Aged↗
PubMed1986

Effects of intravenous and subcutaneous administration of apomorphine on the clinical symptoms of chronic schizophrenics.

The effects of apomorphine, a stimulant of dopamine autoreceptors, were studied in 12 chronic schizophrenics on neuroleptic treatment; both subcutaneous and intravenous administration were used. Apomorphine has been reported to have therapeutic effects in previous studies but, we were not able to confirm any significant and specific differences in psychotic symptoms or tardive dyskinesia scores with apomorphine administration, compared with placebo. These results do not support the importance of dopamine autoreceptors in the regulation of schizophrenic and dyskinetic symptoms in chronic neuroleptic-treated patients.

Adult↗
PubMed1985

Brain muscarinic receptors in senile dementia.

Muscarinic receptors were analyzed in various post-mortem brain samples of 39 patients with different types of dementia and of 30 age-matched controls by the specific binding of [3H]QNB. The diagnoses were verified neuropathologically. The binding of [3H]QNB was significantly decreased in the hippocampus, amygdala and nucleus accumbens in patients with Alzheimer's disease (AD) and with combined type of dementia (CD), whereas in patients with multi-infarct dementia (MID) the binding was not significantly decreased in the limbic areas but only in the caudate nucleus. Of the clinical variables, orofacial dyskinesias in patients with AD but not with MID correlated with low brain weight and with the decreased [3H]QNB binding in the striatum and frontal cortex. The results reveal some differences between AD and MID. Changes in muscarinic receptor binding show that the cholinergic neurons in the limbic system are especially vulnerable in patients with AD and CD.

Aged↗
PubMed1985

Effects of apomorphine on blood levels of homovanillic acid, growth hormone and prolactin in medicated schizophrenics and healthy control subjects.

Two doses of apomorphine (0.005 mg/kg as a subcutaneous injection and 0.015 mg/kg as a 90 min i.v. infusion), and corresponding placebo treatments, were administered to 11 chronic medicated schizophrenic patients and to 8 healthy control subjects. The purpose of the study was to asses the usefulness of drug-induced alterations in the concentration of homovanillic acid (HVA) in plasma as indicators of dopamine autoreceptor sensitivity in the central nervous system. Growth hormone and prolactin in serum were also measured and used as indicators of postsynaptic dopaminergic drug effects. In the control subjects, i.v. apomorphine increased growth hormone in serum from 1.8 +/- 0.2 to 28.3 +/- 4.6 ng/ml and reduced prolactin by 57 +/- 7%. In the patients, apomorphine caused only weak neuroendocrine effects. HVA in plasma was not affected by apomorphine in either group of subjects. The results for growth hormone and prolactin indicate that postsynaptic dopamine receptors in the tubero-infundibular system are antagonized to a considerable degree also during chronic treatment with neuroleptics. The lack of effect of apomorphine on HVA levels suggests that HVA in plasma is not a sensitive indicator of the inhibition of dopamine release caused by small doses of apomorphine and mediated through dopamine auto-receptors. Supersensitivity of this class of receptors could not be demonstrated in our patients, which contrasts with some earlier results.

Adult↗
PubMed1985

Validity of clinical diagnosis in dementia: a prospective clinicopathological study.

With neuropathological diagnosis as the point of reference, the accuracy of clinical diagnosis was studied in a series of 58 demented patients. Alzheimer's disease and multi-infarct dementia were recognised with sensitivities and specificities exceeding 70%, whereas combined dementia as a separate group was relatively unreliably diagnosed. The value of Hachinski's Ischaemic Score in differentiating between Alzheimer's disease and vascular dementias was demonstrated. Its performance was to some extent improved by assigning new weights to the items. In a logistic regression model, fluctuating course, nocturnal confusion, and focal neurological symptoms emerged as features with the best discriminating value, and helped to diagnose correctly 89% of the Alzheimer and 71% of the vascular dementia patients.

Aged↗
PubMed1982

[Tardive dyskinesia].

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Dyskinesia, Drug-Induced↗