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Biomedical subjects

O Lingjaerde

Publications and source records attributed to O Lingjaerde.

At least 55 records · Page 3Linked to original sources

Prevalence of reported sleeplessness in northern Norway in relation to sex, age and season.

As part of a comprehensive population health survey in the municipality of Tromsø, north of the Arctic Circle, men between 20 and 54 years and women between 20 and 49 years were presented a questionnaire containing questions about sleeplessness and its possible association with season. Of the 14,667 respondents, 41.7% of the women and 29.9% of the men said they were sometimes bothered by insomnia. Insomnia not associated with any special time of the year was reported by 16.9% of women and 16.2% of men; insomnia in the "dark period" (midwinter insomnia) was reported by 17.6% of women and 9.0% of men; insomnia in the midnight-sun period or in spring or autumn was much less common. Difficulty falling asleep was the most common type of insomnia, especially in winter and summer. Overall, the frequency of insomnia increased with increasing age, but with some notable differences with regard to type (initial insomnia showed little relation to age, whereas middle and late insomnia increased markedly with age) and seasonal type (insomnia in the midnight-sun period decreased with age, whereas the other seasonal types increased with age).

Adult↗

Attention deficit disorders: a study of peptide-containing urinary complexes.

In several behavioral disorders, we have observed that abnormal amounts of peptides and protein-associated peptide complexes are excreted in the urine. The gel filtration patterns of these excreted substances have some specificity for the different disorders. The urinary excretion of peptide-containing complexes was studied in 91 boys and 13 girls (mean age 9.4 years, range 1-23) with the clinical diagnosis of attention deficit disorder (ADD), with or without hyperactivity. The gel filtration of urine precipitate showed patterns in all patients that were different from those seen in 36 normal controls. Sixty-four patients had increased benzoic acid-glycoprotein-peptide complexes in the late peaks. The symptoms of all these patients fit the criteria for diagnosis of attention deficit disorder with hyperactivity (ADDH). Thirty-five patients showed reduced amounts of uric acid complexes in the late peaks. Clinically, this group, with the exception of three patients, fit the criteria for diagnosis of attention deficit disorder without hyperactivity. Five patients showed reduced amounts of all urinary complexes; four of these were hyperactive. Moderate exercise in control children did not change the urinary pattern. One urinary peptide fraction from hyperactive patients, purified to homogeneity, increased the uptake of 14C[5-HT] in platelets. Strict clinical, neuropsychological, and psychophysiological selection of the patients reduced the heterogeneity of the patterns. Although more studies are needed, the findings seem promising for the possibility of developing biochemical tests that may be helpful diagnostically.

Adolescent↗

The uptake, storage, and efflux of serotonin in platelets from migraine patients.

A recently developed method for analysing 5-hydroxytryptamine (5-HT) efflux from platelets preloaded with a small amount of 14C-5-HT enables the assessment of the relative size of the granular and the cytoplasmatic pools of 5-HT within the platelets and of the rate of spontaneous efflux from these two compartments. This method, together with conventional assessment of the 5-HT uptake measures Km and Vmax, was applied in this study, comparing platelets from 14 patients with common migraine and 10 patients with classic migraine with platelets from 25 healthy controls. All patients were unmedicated and in an attack-free period. Neither the total patient group nor either of the two subgroups differed significantly from the control group on any measure of 5-HT uptake or efflux. However, two differences approached the conventional significance level: the relative size of the granular compartment (Compartment III) was larger for classic than for common migraine, and the efflux rate from Compartment III was shorter for classic migraine than for the healthy controls (P approximately 0.10 in both cases). Further studies are required to show whether these differences are real and, if so, whether they have any relevance for the pathogenesis of migraine attacks.

Adolescent↗

Effects of the benzodiazepine receptor ligands midazolam, Ro 15-1788, and Ro 5-4864, alone and in combinations, on platelet serotonin uptake.

The benzodiazepine (BZ) agonist midazolam, the BZ antagonist Ro 15-1788, and the peripheral BZ binding site ligand Ro 5-4864 have been assessed, separately and in combinations, as to their effect on the active uptake of serotonin (5HT) in human blood platelets in vitro, in an artificial, protein-free medium. Midazolam had a moderate noncompetitive (or mixed competitive/noncompetitive) inhibitory effect on the uptake. This effect was not influenced by Ro 15-1788, which in itself had only a very weak inhibitory effect. Ro 4-5864 showed in several independent experiments (but not always) a biphasic inhibitory effect, with a moderate but significant inhibition in the concentration range of about 10(-8) to 10(-6) M, and a stronger, noncompetitive inhibitory effect above 10(-6) M. When Ro 5-4864 was tested in the presence of a fixed concentration of midazolam (4 X 10(-6) M), the inhibitory effect of the former was markedly reduced (at higher concentrations), eliminated (at intermediate concentrations), or even reversed into a relative stimulatory effect (at low concentrations). Thus, low concentrations of Ro 5-4864 reduced the inhibitory effect of midazolam. A possible explanation of this interaction is that low concentrations of Ro 5-4864 have both an inhibitory and a stimulatory effect on platelet 5HT uptake (often seen to vary in relative strength between experiments), and that the stimulatory component is unmasked in the presence of a drug that already has an inhibitory effect, probably mediated by the same site.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzodiazepines↗

Relationship between clinical effects, serum drug concentration and serotonin uptake inhibition in depressed patients treated with citalopram. A double-blind comparison of three dose levels.

Three dose levels (5, 25, and 50 mg once daily) of the selective serotonin uptake inhibitor citalopram were compared in a four-week, double-blind trial in depressed patients. Serum levels of citalopram and desmethylcitalopram, and the inhibitory effect of serum on serotonin uptake by fresh platelets, were assessed once weekly during the trial. The serum concentrations of citalopram were highly correlated with inhibition of serotonin uptake. Less of the metabolite was found, it being detected only in the higher dose groups. Steady state levels of citalopram, attained after 1 week, were linearly related to dose. The relationship between improvement (percentage reduction in total score on the Montgomery-Asberg Depression Rating Scale) and serum level of citalopram indicated a lower limit of effect in endogenous depression at about 100 nM, corresponding to an average dose of 15 mg. Marked improvement was seen in ten patients with steady state levels in the range 70 to 335 nM. The ten nonendogenously depressed patients had steady state levels from 15 to 620 nM; complete remission was seen in the three with the lowest levels (15-25 nM). No significant correlation was found between serum drug level and the few reported side effects.

Adult↗

Lactate-induced panic attacks: possible involvement of serotonin reuptake stimulation.

In panic disorder patients, panic attacks can be precipitated with great regularity by intravenous infusion of lactate. The mechanism behind this effect, as well as the mechanism behind the spontaneously occurring panic attacks, are unknown, however. The author draws attention to the fact that lactate as well as pyruvate stimulate serotonin uptake in human blood platelets, and suggests that lactate infusion may stimulate serotonin reuptake also in central serotonergic neurons, thereby decreasing serotonergic activity. This may possibly induce anxiety by reducing the inhibitory serotonergic influence on locus ceruleus. This mechanism--which may not be the only one involved in lactate-induced panic attacks--would easily explain the effect of tricyclic antidepressants, like imipramine, against lactate-induced panic.

Blood Platelets↗

Insomnia during the "dark period" in northern Norway. An explorative, controlled trial with light treatment.

Midwinter insomnia (MI) is an initial type insomnia that is typically seen north of the Polar Circle during the "dark period", when the sun does not rise above the horizon. The cause of MI is not known, but it seems reasonable to assume that it is the expression of a phase delay of the sleep-wake cycle, due to lack of the entraining effect of normal daylight. Based on his hypothesis, we have studied the effect of intensive light exposure (2000-2500 lux for half an hour between 7.30 and 8.30 a.m. for 5 days) on selected sleep and endocrinological variables (the latter will be reported elsewhere) in nine subjects with typical MI and eight healthy controls. After light exposure, the MI subjects had a significantly shortened sleep latency and a nonsignificant increase in total sleep time. Before light exposure, the MI subjects reported significantly less drowsiness in the evening than in the morning, whereas the opposite was true after light exposure. No significant changes were seen in the control group. The results of this study give some support to the delayed phase hypothesis.

Adult↗

From clomipramine to mianserin: therapeutic relevance of interactions with serotonin uptake and storage, as studied in the blood platelet model.

Inhibition of active serotonin uptake into neurones and platelets is a common effect of tricyclic and related antidepressants, and has been regarded as one of the more important mechanisms of action of such drugs. However, as is shown in this survey, the antidepressants vary widely in their potency as inhibitors of platelet serotonin uptake, and they also differ in the type of inhibition kinetics, from purely competitive to mixed competitive/noncompetitive. The therapeutic relevance of this effect is discussed. Serotonin uptake inhibition seems to be one of several mechanisms for obtaining the required normalization of monoamine dysfunction in depression. Analysis of efflux from platelets preloaded with a moderate amount of 14C-serotonin provides information on the storage and compartmentation of serotonin in the platelets, and on the rate of efflux from the different compartments. When present during the preloading phase, some antidepressants seem to produce a relative increase in serotonin in the granular storage compartment when compared to the smaller cytoplasmic compartment. This effect is in some respects opposite to that exerted by reserpine, and possibly may be pharmacologically relevant.

Antidepressive Agents↗

Platelet serotonin uptake inhibition as a basis for monitoring antidepressant drug treatment.

A quantitative method for measuring serotonin uptake inhibition in fresh platelets incubated in diluted plasma (stored frozen until analyzed) from patients treated with tricyclic and related antidepressants is described. The method was used in a clinical trial comparing the specific serotonin uptake inhibitor zimelidine with the mixed serotonin-norepinephrine uptake inhibitor desipramine in patients with endogenous depression, and correlating this with plasma drug concentration assessment. The bioassay, based on the use of one single, low concentration of serotonin, was found to be very sensitive and to have a high reliability (coefficient of variation about 2% as calculated from duplicate samples), and to correlate highly with log plasma concentration of zimelidine, norzimelidine, and of desipramine. This bioassay may have some advantages in relation to plasma drug concentration assessment, but only future studies can show whether it provides a better basis for antidepressant drug monitoring.

Adult↗

Effect of midazolam, flunitrazepam, and placebo against midwinter insomnia in northern Norway.

Forty-three outpatients with "midwinter insomnia" (an early type insomnia commonly seen north of the Polar Circle when the sun stays below the horizon) were randomly allocated to one of three treatment groups, receiving either 15 mg midazolam, 1 mg flunitrazepam, or placebo, for 5 nights, double blind, after 3 nights without drug. In all three groups, this was followed by 5 nights on placebo (single blind). Several subjective sleep variables were recorded every morning, some variables also at noon. Placebo had practically no effect on any sleep variable, whereas both active drugs markedly improved sleep with regard to the following variables: sleep latency, number of awakenings, total duration of sleep, quality of sleep, total evaluation of sleep, and feelings of drowsiness in the morning and at noon. In the withdrawal period, patients who had received active drug showed a deterioration of sleep on most variables, but not beyond the baseline level. A true "rebound insomnia" could thus not be demonstrated. There was no significant difference in any of the variables between midazolam and flunitrazepam treatment. Side effects were reported by very few patients. Midazolam seems to be as effective as flunitrazepam in this type of insomnia, in spite of its much shorter biological half-life.

Adolescent↗

A double-blind comparison of zimelidine and desipramine in endogenous depression.

Zimelidine, a specific 5HT uptake inhibitor (final dose 225 mg), and desipramine, mainly a noradrenaline uptake inhibitor (final dose 150 mg), were given in random order to 24 in- and out-patients fulfilling the Research Diagnostic Criteria for Major Depressive Disorder, definite or probable endogenous type, for a 3-week treatment period. Nonresponders were crossed over to the other drug for another 3 weeks. There was a nonsignificant trend towards more overall improvement on desipramine. Some patients in both groups showed very little change during 3 weeks, indicating a bimodal distribution of response to either drug. Several nonresponders improved markedly upon direct crossing over to the other drug. There were few and mild side effects on both drugs, with no significant difference between them. No significant correlation was found between improvement and plasma concentrations of zimelidine, norzimelidine, or desipramine, whereas a significant positive correlation was found between improvement and platelet serotonin uptake inhibition (measured in fresh platelets incubated in diluted plasma from the patients) in zimelidine-treated patients.

Adolescent↗

Serotonin uptake and efflux in blood platelets from untreated and neuroleptic-treated schizophrenics.

Earlier studies on platelet serotonin uptake in schizophrenia have given equivocal results. In this study, platelet serotonin uptake in diluted plasma was assessed in 23 drug-free and 19 neuroleptic-treated schizophrenics, compared to 70 controls. The maximal uptake rate, Vmax, was slightly but significantly lower in drug-free schizophrenics than in the controls. In neuroleptic-treated patients there was a nonsignificant trend in the same direction. The "affinity constant" Km was significantly elevated in neuroleptic-treated schizophrenics compared to both controls and drug-free patients. Assessment of serotonin uptake in platelets resuspended in an artificial medium gave no definite answer whether reduced Vmax in plasma is due to a plasmatic or a platelet abnormality. Spontaneous efflux of serotonin from preloaded platelets did not differ significantly between patients and controls.

Adolescent↗

Plasma and erythrocyte levels of methotrimeprazine and two of its nonpolar metabolites in psychiatric patients.

Methotrimeprazine (levomepromazine) has two major metabolites in man: N-monodesmethyl methotrimeprazine, which is pharmacologically active and almost as potent as the parent drug; and methotrimeprazine sulfoxide, which is much less active. Blood levels and the distribution between plasma and erythrocytes of methotrimeprazine and the two metabolites were studied in five psychiatric patients on oral methotrimeprazine and after incubation of the compounds in blood from healthy volunteers. The concentrations were measured separately in plasma and erythrocytes by gas chromatography with a nitrogen detector, and the concentrations in whole blood were calculated from the plasma and erythrocyte concentrations. In four of the five patients the blood levels of both metabolites were similar to or higher than the levels of the parent drug. A large interindividual variation was observed in the plasma-erythrocyte concentration ratios. The mean ratios in all individuals were 1.76, 0.57, and 3.02 for methotrimeprazine, N-monodesmethyl methotrimeprazine, and methotrimeprazine sulfoxide, respectively. The relatively high blood concentrations of N-monodesmethyl methotrimeprazine suggest that this metabolite may contribute significantly to the therapeutic action and side effects of oral treatment with methotrimeprazine.

Adult↗