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Biomedical subjects

P Hartvig

Publications and source records attributed to P Hartvig.

At least 109 records · Page 6Linked to original sources
PubMed1990

Striatal binding of 11C-NMSP studied with positron emission tomography in patients with persistent tardive dyskinesia: no evidence for altered dopamine D2 receptor binding.

Dopamine D2 receptor binding characteristics were studied by positron emission tomography (PET) using N-11C-methyl spiperone as receptor ligand in patients on longterm treatment with neuroleptic drugs and in control subjects. Eight of the patients had symptoms of tardive dyskinesia whereas three patients did not have any symptoms. Control subjects comprised 5 healthy volunteers and 7 patients with pituitary tumors. All patients had been free of neuroleptic drugs for at least 4 weeks. The time dependent regional radioactivity in the striatum was measured and the receptor binding rate, k3, proportional to receptor number, Bmax and association rate for the receptor was calculated in relation to the cerebellum. The lack in difference in k3 values between TD patients, neuroleptic treated patients without TD and control subjects throws doubt on the hypothesis that changes in striatal D2 dopamine receptor number or binding affinity is an etiological mechanism for persistent TD.

Aged↗
PubMed1990

Behavioral effects after intrathecal administration of cholinergic receptor agonists in the rat.

Behavioral effects of nicotine and cytisine, and the cholinesterase inhibitors physostigmine and 9-amino-1,2,3,4-tetrahydroacridine (THA), administered intrathecally (IT) at the lumbar level in the rat have been evaluated. Antinociceptive dose relationships were established using the tail immersion test. Total activity, locomotion and rearing were also measured in computerized test boxes. The nicotinic receptor antagonist, mecamylamine, and the muscarinic receptor antagonist, atropine, were used to study the selectivity of the effects. Physostigmine and THA significantly decreased total activity, locomotion and rearing as compared to control animals. The motor effects of physostigmine were completely antagonized only partly. Mecamylamine had no antagonistic effect. Nicotine did not affect any activity parameter. Cytisin reduced total activity and locomotion 1-6 min after dose. IT physostigmine, 15 micrograms, increased tail immersion latency for 30 min. No significant increase in response latency in this test was observed after the IT administration of nicotine or THA, whereas cytisine elicited a small increase. The IT administration of THA, nicotine and cytisine was also associated with gnawing, vocalization and hyperactivity and in the case of THA, diarrhoea. These effects were blocked by mecamylamine. Physostigmine antinociception as well as the behavioral effects including total activity, locomotion and rearing caused by physostigmine and by THA are most probably due to an action on spinal muscarinic receptors. Nicotinic receptors do not seem to be involved in spinal antinociception. Some aversive behavioral effects caused by the IT administration of nicotinic receptor agonists could, however, be attenuated by the spinal administration of the antagonist mecamylamine, which may indicate the involvement of nicotinic receptors in afferent sensory transmission.

Alkaloids↗
PubMed1990

Decreased uptake and binding of 11C-nicotine in brain of Alzheimer patients as visualized by positron emission tomography.

Positron emission tomography of the brain following intravenous injection of (+) (R) and (-) (S) N-[11C-methyl]nicotine showed a marked reduced uptake of both isomers, especially the (R) form, in Alzheimer patients as compared to age-matched controls. The significantly larger difference between the uptake values of the (S)- and (R)-enantiomers of 11C-nicotine in Azheimer brains may be of diagnostic value.

Aged↗
PubMed1990

Striatal kinetics of [11C]-(+)-nomifensine and 6-[18F]fluoro-L-dopa in Parkinson's disease measured with positron emission tomography.

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.

Adult↗
PubMed1990

Functional and pharmacokinetic studies of tetrahydroaminoacridine in patients with amyotrophic lateral sclerosis.

Assuming the presence of clinically significant cholinergic hypofunction in amyotrophic lateral scleroses (ALS), seven patients with ALS were treated with 100-200 mg tetrahydroaminoacridine (THA) together with 11 g lecithin daily for up to 7 weeks. In a separate experiment pharmacokinetics and effects on muscle strength and neurophysiological parameters were studied following the injection of 30 mg THA intravenously. Following the injection of THA an increase in muscle strength was observed in two patients. There were no consistent pharmacokinetic differences that could explain the effect on intravenous THA on muscle strength in these two patients. The plasma clearance of THA was high and the oral bioavailability low with large interindividual differences (6-36%). No beneficial effect was seen during oral medication and side-effects were common. There were no conclusive changes observed regarding neurophysiological parameters after drug administration. THA has probably no place in the treatment of ALS.

Administration, Oral↗
PubMed1990

Regional distribution of the opioid receptor agonist N-(methyl-11C)pethidine in the brain of the rhesus monkey studied with positron emission tomography.

The regional distribution and kinetics in the brain of Rhesus monkeys of N-(methyl-11C)-pethidine have been studied by positron emission tomography, PET. 11C-Pethidine reached the brain with peak radioactivities appearing within 6-10 min. after administration. Highest radioactivities were measured in areas corresponding to the thalamus, the striatal area and also the lowest transection of the temporal lobes, with an uptake of 2.7-3.1 times the homogenous dilution of the radioactive dose. Low radioactivities were seen in the cerebellum and the occipital lobes. This distribution corresponds to the regional density of opioid receptors using in vitro binding techniques. The 11C-pethidine derived radioactivity left the brain with an initial half-life of 40-60 min., followed by an elimination which paralleled the plasma elimination of unlabelled pethidine. After pretreatment of the monkey with a small dose of naloxone, the radioactivities decreased about 40% in areas corresponding to the thalamus, striatum and lowest section of the temporal lobes, indicating competition for the same binding sites. By the use of a three-compartment model, it was possible to get an estimate of 11C-pethidine receptor binding characteristics in the brain. The ratio of Kon/Koff, equal to Bmax./Kd, was 0.06-0.1. This indicates that pethidine is bound with low affinity to the opioid receptors and is a poor ligand for studies of opioid receptor function with PET. Brain kinetics of 11C-pethidine is mainly determined by its blood kinetics.

Animals↗
PubMed1990

Effects of intrathecal injection of the adenosine receptor agonists R-phenylisopropyl-adenosine and N-ethylcarboxamide-adenosine on nociception and motor function in the rat.

R-phenylisopropyl-adenosine, which has an affinity for the adenosine A1 receptor higher than that for the A2 receptor, and N-ethylcarboxamide-adenosine, which has near equal affinity for the A1 and A2 receptors, were injected intrathecally into rats to evaluate differences in antinociceptive effect and motor impairment. Using the tail-immersion test, both compounds had antinociceptive effects. Motor function was evaluated during spontaneous movement in a free space. N-ethylcarboxamide-adenosine rapidly impaired motor function even after low intrathecal doses. R-phenylisopropyl-adenosine also induced motor impairment, but only after high intrathecal doses, and onset was much slower. These results suggest that the receptor selectivity of R-phenylisopropyl-adenosine is diminished at higher doses and that the motor impairment is an A2-receptor-mediated effect. A selective A1 receptor agonist, e.g., R-phenylisopropyl-adenosine, which produces a good antinociceptive effect without motor impairment, is more promising as a drug of possible use for the future treatment of clinical pain.

Adenosine↗
PubMed1989

[The concept of disease and handicap in the National Insurance Act. Clinical features, epidemiology and medical ethical points of view].

The article discusses the physicians' problems in their work corrected to medical certification for a National Disability Pension etc. The most prevalent problems are quantitative assessment of disability in general, and diagnostic understanding of the growing number of ill-defined conditions with somatic and psycho-social components in particular. The article considers physicians' ethical weighing up of obligations both to the individual patient/applicant and to proper use of public funds. A public discussion and clarification of the place of National Disability Pension in the solving of social problems is advised.

Persons with Disabilities↗
PubMed1989

[PET--new ways inside the body].

Using positron-emitting short-lived radionuclide tracers, a wide range of substances can now be labelled without their biological properties being affected. Positron emission tomography (PET) enables the distribution and metabolism of the labelled substance to be studied in different organs. By providing quantitative, locational, functional and biochemical information difficult to obtain by other means, PET opens up new possibilities, both diagnostic, pathophysiological and therapeutic, in a broad spectrum of medical practice. The development of the technique is described, with particular reference to its use at Uppsala.

Abdominal Neoplasms↗
PubMed1989

Striatal and frontal cortex binding of 11-C-labelled clozapine visualized by positron emission tomography (PET) in drug-free schizophrenics and healthy volunteers.

The binding of 11C-labelled clozapine in the brain was studied in three drug-free schizophrenic patients and in three healthy volunteers. High radioactivities were found in the striatum and in the frontal cortex. The rate constant k3, which is proportional to receptor association rate and the number of receptors, was lower in the frontal cortex compared to the striatum. No obvious difference between the two brain areas was seen for the dissociation rate constant from the receptors (k4). Two schizophrenic patients were reexamined after pretreatment with haloperidol, one after 6 weeks of treatment with a low oral dose, the other one after an IV injection 1 h before 11C-clozapine was given. After haloperidol pretreatment, the binding of 11C-clozapine in striatum and frontal cortex was reduced, more pronounced in the striatum, indicating competition for D-2 dopamine binding sites. Our finding indicates that clozapine has an affinity for a receptor population in the frontal cortex that is predominantly not of the dopamine-D2 type. This feature might be of importance for the unique clinical profile of the drug.

Adult↗
PubMed1989

Uptake and regional distribution of (+)-(R)- and (-)-(S)-N-[methyl-11C]-nicotine in the brains of rhesus monkey. An attempt to study nicotinic receptors in vivo.

N-[methyl-11C] nicotine (11C-nicotine) was given intravenously to monkeys and the uptake and regional distribution of radioactivity was followed in the brain using positron emission tomography (PET). The 11C-radioactivity in the brain peaked within 1-2 min and then rapidly declined. Pretreatment with unlabelled nicotine (10 micrograms/kg) reduced the uptake of 11C-radioactivity to the brain by 30%. The uptake of radioactivity was higher following (+)11C-nicotine than (-)11C-nicotine. Both enantiomers were distributed in a similar manner within the brain. When animals were infused with a peripheral nicotinic blocker (trimetaphan) the uptake of radioactivity to the brain was lower following (+)11C-nicotine compared to (-)11C-nicotine. The amount of radioactivity was high in the occipital cortex, thalamus, intermediate in the frontal cortex and low in white matter in (-)11C injected monkeys while no regional difference in distribution of 11C-radioactivity was observed after injection of (+)11C-nicotine.

Animals↗