Biomedical subjects
Publications and source records attributed to A Laihinen.
We investigated dopamine D1 receptors in the putamen and caudate nucleus with positron emission tomography in six patients with narcolepsy and five healthy controls using [11C]NNC 756 as ligand. The caudate-to-cerebellum and putamen-to-cerebellum ratios of [11C]NNC 756 were within normal limits in patients with narcolepsy. No evidence of increased D1 receptor binding in narcolepsy was found.
The monoamine transporter was studied in 4 healthy controls and 5 patients with early Parkinson's disease (PD), who had not received any antiparkinsonian medication, by means of positron emission tomography (PET) using two novel ligands, [11C]beta-CIT and [11C]beta-CFT. Both ligands showed highest uptake in the striatum. There was intermediate accumulation of activity in the thalamus and midbrain, which was more marked for [11C]beta-CIT than for [11C]beta-CFT. In the cortical areas, uptake of both ligands was not different from that seen in the cerebellum. In the controls, the putamen-to-cerebellum and caudate-to-cerebellum ratios for [11C]beta-CFT were higher than those for [11C]beta-CIT (putamen: 3.15 +/- 0.39 for [11C]beta-CFT, and 1.84 +/- 0.10 for [11C]beta-CIT; caudate: 3.15 +/- 0.31 for [11C]beta-CFT, and 1.95 +/- 0.17 for [11C]beta-CIT). Reduction from mean control value in PD patients was greater for [11C]beta-CFT (45% in the putamen contralateral to the predominant symptoms, P < 0.001) than for [11C]beta-CIT (20%, P > 0.05). [11C]beta-CFT uptake in the caudate nucleus was also diminished in PD patients (to 80% of the control mean, P < 0.05), whereas [11C]beta-CIT was within normal range (reduced to 90% of the control mean). These results indicate that both [11C]beta-CIT and [11C]beta-CFT are useful PET ligands to study brain monoamine transporter in healthy controls and in patients with PD. However, [11C]beta-CFT seems superior to [11C]beta-CIT in this respect.
Striatal dopamine D2 receptors were studied, using positron emission tomography (PET), in 10 patients with early Parkinson's disease without any antiparkinsonian medication and in 14 healthy controls. [11C]Raclopride was used as ligand and an equilibrium method was applied. The maximum count of receptors (Bmax) and their dissociation constant (Kd) were calculated according to the Scatchard principle. In parkinsonian patients, the Bmax of D2 receptors was increased in the putamen contralateral to the predominant symptoms, as compared to the opposite putamen, by 33% (p = 0.0008). In the caudate nucleus no significant side to side differences was noted. On comparison with age-matched healthy controls, Bmax values in the putamen (p = 0.0012) but not in the caudate nucleus contralateral to the side of predominant clinical symptoms were increased in PD patients. The Kd values were unchanged. The difference in putaminal Bmax values between the opposite hemispheres correlated with the difference in the severity of parkinsonian motor symptoms between the two body sides (r = 0.69, p = 0.03). The present results show that there is both a relative and absolute increase in the number of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson's disease.
We investigated dopamine D2 receptors in the caudate nucleus and putamen with positron emission tomography in seven patients with narcolepsy and seven healthy controls by using [11C]raclopride as a ligand. We applied an equilibrium method and Scatchard principle to give a quantitative estimation of the number (Bmax) and dissociation constant (Kd) of the receptors. Both the Bmax and Kd were within the normal range in the caudate nucleus and putamen in narcoleptic patients. We found no evidence for increased D2 receptor binding in narcolepsy.
[11C]Raclopride uptake to dopamine D2 receptors was investigated with positron emission tomography (PET) in patients with early Parkinson's disease at the time of the diagnosis and after a half-year interval. During this progressive period of the disease, the patients received no antiparkinsonian medication. The upregulation of striatal D2 receptors, which was seen in all patients already at the time of the diagnosis, persisted. Although the patients initially showed unilateral disease, they had developed bilateral symptoms by the time of the second PET scan, but the disease was still asymmetric. The present results show that the relative increase in [11C]raclopride uptake in the striatum contralateral to the symptoms as compared with the opposite striatum will be preserved even during the progression of the disease, provided that the symptoms show clear-cut asymmetry.
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.
Twenty patients with advanced idiopathic Parkinson's disease were studied, all having a deteriorating response to levodopa and suffering from daily fluctuations in disability. A double-blind randomized cross-over study was conducted. Basic levodopa and anticholinergic treatment was continued unchanged in all patients. The dose increment period of 4-8 weeks was followed by a 4 week treatment period on a fixed optimal dose. In both treatment groups the mean optimal daily dose of lisuride was 1.3 mg (range 0.2-2.4 mg) and that of bromocriptine about 15 mg (range 3.75-30.0), without any significant differences between the treatment groups. The addition of lisuride or bromocriptine to levodopa treatment resulted in a significant and equal further improvement of parkinsonian disability. The therapeutic profiles of both lisuride and bromocriptine were similar. There was significantly more improvement in tremor than in other parkinsonian symptoms. Both lisuride and bromocriptine elicited a significant improvement in fluctuations of disability. No significant differences between the treatments were observed. The occurrence of clinical side effects seemed to be similar with both treatment regimens. In advanced parkinsonian patients the therapeutic efficacy of lisuride seems to be equal to that of bromocriptine as far as parkinsonian disability and fluctuations in disability are concerned.
PET studies were performed to investigate the effects of a new cathechol-O-methyltransferase (COMT) inhibitor, nitecapone (OR-462 [3-(3,4-dihydroxy-5-nitrobenzylidene)- 2,4-pentadione]), on the accumulation of dopamine in the striatum and whether it is able to improve [18F]6-fluorodopa imaging of the brain. Altogether, three patients with Parkinson's disease (PD) and three normal volunteers were examined, first without nitecapone and then with an oral dose of 100 mg of nitecapone 1 hour before the IV injection of 3 mCi of [18F]6-fluorodopa. High-pressure liquid chromatography analysis of arterial plasma samples showed a significant reduction in the metabolic conversion rate from [18F]6-fluorodopa to [18F]3-O-methylfluorodopa after the administration of nitecapone. PET studies showed that nitecapone significantly (p less than 0.05) increased the [18F]6-fluorodopa accumulation in the striatum both in PD patients and normal controls; the magnitude of this increase was 20.0 +/- 5.5% (mean +/- SEM). The ratio of radioactivity in the striatum and arterial plasma was increased 39.0 +/- 5.0% (mean +/- SEM) after the administration of nitecapone. Consequently, the quality of PET images after OR-462 was better, which has implications for future [18F]6-fluorodopa studies. In addition, COMT inhibition may have clinical advantages by improving levodopa treatment in PD.
Striatal dopamine D1 and D2 receptors were investigated in 49 patients with Parkinson's disease (PD) and 33 age-matched controls with [3H]SCH 23390 and [3H]spiroperidol as ligands respectively. A full Scatchard analysis giving Bmax and Kd values was performed. In the caudate nucleus, a small but significant decrease in the number of D1 and D2 receptors was seen, whereas in the putamen the number of dopamine receptors was unchanged. Treatment with neuroleptics was found to increase the number of D2 receptors both in the caudate nucleus and putamen. The number of neither D1 nor D2 receptors correlated neither with the duration of disease or levodopa treatment of the patients nor with the post-mortem delay or storage time of the samples. Furthermore, no association was found between either D1 or D2 receptor number and clinical variables of the patients. The activity of choline acetyltransferase (ChAT) was found to be unchanged in the striatum, whereas a marked decline was seen in the hippocampus and cortical areas, indicating that intrinsic striatal cholinergic neurons are not affected in PD. The present results suggest that there is a modest decline in the number of striatal dopamine D2 receptors in advanced patients with PD at the end stage of the disease.
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In many skin diseases, itching and scratching is a vicious circle, which prolongs the disease. The aim of this study was to investigate the mechanisms which make itching skin diseases more chronic. The patients consisted of seven diagnostic groups--79 inpatients all together. The dermatoses were: dermatitis herpetiformis, lichen ruber planus, chronic eczema, atopic eczema, neurodermatitis circumscriptus, prurico psychogenous and lichen obtusus corneus. Both psychiatric and dermatological examinations were performed. Psychiatric disturbance was clearly greater than in the average population. The chronifying mechanisms were the following: personality disorder as a treatment problem; emotional infantility, which makes the illness itself an important security factor; itching and scratching as pleasure and content of life; the accumulation of various other diseases, both somatic and psychiatric; and untreated depression. Information was obtained on the possibilities of psychiatric treatment and psychosocial rehabilitation.
Striatal dopamine D-1 receptor binding was investigated in vivo with positron emission tomography (PET) in five patients with early Parkinson's disease using [11C]-SCH 23390. All patients had predominantly unilateral symptoms and showed a significant reduction in the accumulation of [18F]-6-F-DOPA in the striatum contralateral to the symptoms. None of the patients had received any antiparkinsonian medication. The striatal and cerebellar radioactivity was measured and corresponding striatum/cerebellum ratios were counted. The mean striatum/cerebellum ratio of [11C]-SCH 23390 binding was symmetric between the hemispheres. By contrast, the striatum/cerebellum ratio of [11C]raclopride binding, labelling dopamine D-2 receptors, was increased significantly in the hemisphere contralateral to the symptoms as compared with the opposite hemisphere. Thus, the present results show that the behaviour of striatal D-1 and D-2 receptors is different in early Parkinson's disease.
Striatal dopamine D2 receptor binding was studied in vivo with positron emission tomography in seven patients with early Parkinson's disease using [11C]-raclopride. The patients had unilateral symptoms and none of them had received levodopa treatment. The accumulation of [11C]-raclopride in the striatum was rapid and reached a steady state at approximately 40 min after injection. The binding of [11C]-raclopride was measured in the striatum and cerebellum: The total striatal radioactivity in both hemispheres was counted and the respective striatum/cerebellum ratios were calculated. The striatum/cerebellum ratio of [11C]-raclopride binding was significantly (p less than 0.01) increased in the hemisphere contralateral to the parkinsonian symptoms as compared with the opposite hemisphere. Thus, this study demonstrates that there is denervation supersensitivity in dopamine D2 receptor binding in early Parkinson's disease.
The kinetics in brain of the dopamine reuptake blocking agent [11C]-(+)-nomifensine and the L-dopa analogue 6-[18F]fluoro-L-dopa were compared in 3 patients with idiopathic Parkinson's disease and age-matched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nucleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-[18F]fluoro-L-dopa utilization and [11C]-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinson's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals.
The distribution of SP receptors was studied both in the normal human brain and in the parkinsonian brain by means of tritiated SP. The highest levels of binding were found in the striatal areas and in the NbM. The distribution was similar to that found in laboratory animals in earlier studies. In PD the binding was significantly reduced in the NbM and parietal cortex as compared with controls. The level of SPLI was reduced in both parts of the SN, in the NbM, and in the GPi.
Nine parkinsonian patients were studied during one night using the static charge sensitive bed (SCSB) method for the monitoring of respiration, ballistocardiogram (BCG) and body movements. The parkinsonian sleep was more restless than that of the controls. As the SCSB-defined levels of autonomic nervous activity were concerned, the amount of motor active wakefulness (MAW) was significantly (P less than 0.05) increased in parkinsonian patients, who also had less quiet sleep (P less than 0.05) than the controls. Parkinsonian tremor was present during 29.8 +/- 15.8% of the time in bed. Usually it was observed during wakefulness; it disappeared when the patient fell asleep. The frequency of turning-over events in bed was smaller in the parkinsonian patients than in the controls (P less than 0.05). When the heart rate changes associated with sleep movements were studied it was found that the parasympathetic deceleration component in the parkinsonian patients was absent. The motor dysfunction associated with Parkinson's disease is reflected in many ways in the sleep movement activity. Sleep disturbances in PD seem to be secondary in character; i.e. they can be due to impaired motor functions like turning around in the bed, or due to impaired arousal mechanisms during sleep.
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