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Biomedical subjects

G M van Kempen

Publications and source records attributed to G M van Kempen.

At least 19 recordsLinked to original sources

The effect of m-CPP on tics and obsessive-compulsive phenomena in Gilles de la Tourette syndrome.

RATIONALE: Family genetic and phenomenological studies support an interrelationship between Gilles de la Tourette syndrome (GTS) and obsessive-compulsive disorder (OCD). Some authors consider GTS as part of a serotonergically mediated cluster of OCD spectrum disorders. OBJECTIVE: To study serotonergic mechanisms in GTS, the effect of the relatively selective 5-HT2c agonist meta-chlorophenylpiperazine (m-CPP) was assessed. METHODS: We studied the behavioural effects of m-CPP on tics, obsessions, compulsions and impulsions of GTS. Twelve medication-free GTS patients (ten men, two women) were included in a single dose 0.5 mg/kg oral m-CPP challenge study with a double-blinded placebo-controlled cross-over design. Global symptom scores, target symptom scores as well as biochemical measures were followed up to 24 h after baseline. RESULTS: While m-CPP caused a significant rise in plasma cortisol and prolactin levels, no significant effects were found on the tics, obsessions and compulsions. Impulsions showed a trend to ameliorate. CONCLUSIONS: This study does not support a predominant role for 5-HT on the tics in GTS. The trend of impulsions to ameliorate after m-CPP can be interpreted as circumstantial support for impulsivity-related 5-HT hypofunctionality in GTS. However, the large variability of m-CPP plasma concentrations found in this study casts doubts upon the reliability of m-CPP as a probe for challenge studies.

Adult

Mood correlates with blood serotonin, but not with glucose measures in patients with recurrent suicidal behavior.

Depressive mood and impulsive-aggressive behavior are relevant to suicidal behavior and have been associated with decreased central serotonergic function. Impulsive behavior and aggression have also been related to abnormal glucose metabolism. To investigate these relationships further, blood serotonin (5-HT), blood glucose measures (glycated hemoglobin (HbA1C) and fructosamine) and self-reported depressive symptoms and anger were repeatedly measured, during a 1-year follow-up, in 106 patients who had recently attempted suicide for at least a second time. A major DSM-III-R Axis I diagnosis or use of antidepressants were reasons for exclusion. Intra-individual variations in blood 5-HT were inversely correlated with variations in depressive mood, self-depreciation, and anger, and positively with variations in fructosamine. Intra-individual variations of HbA1c or fructosamine were not correlated with mood. Mean blood 5-HT levels per patient were positively correlated with mean scores of depression and self-depreciation. The contrast between the intra-individual and the inter-individual correlations may reflect a difference between short- vs. long-term effects. The results do support an association between serotonergic function and mood, but not between glucose metabolism and mood, in recurrent suicide attempters.

Adolescent

Plasma levels of arginine vasopressin elevated in patients with major depression.

Mentally healthy subjects show increased plasma concentrations of the neuropeptides, arginine vasopressin (AVP) and oxytocin (OT), under conditions of stress, but data are lacking about plasma concentrations of AVP and OT in patients with major depression. We thus assessed plasma concentrations of AVP and OT in patients with major depression (n = 52) and healthy controls (n = 37). Mean plasma AVP concentrations were higher in the group of depressed patients than in controls. A subgroup of 16 patients showed very high levels of plasma AVP, but no other feature differentiating this subgroup from the other patients was found. In-patients showed higher plasma AVP levels than out-patients, and melancholic patients had higher plasma AVP levels than did nonmelancholic patients. Plasma AVP levels were slightly related to psychomotor retardation and significantly inversely to neuroticism. Patients' plasma OT concentrations had a wider range than in controls. AVP and AVP-mediated functions may be a factor in the clinical picture of depression, possibly by influencing the activity of the hypothalamic-pituitary-adrenal axis.

Adrenocorticotropic Hormone

Suicidality, circadian activity rhythms and platelet serotonergic measures in patients with recurrent suicidal behaviour.

The circadian activity rhythm was assessed over a one-week period using a wrist-worn activity monitor in 59 patients with a history of recurrent suicide attempts. In 40 of these patients a second recording was made 6 months later. Platelet serotonin (5-HT) and monoamine oxidase-B activity (MAO) were measured. Suicidal ideation, borderline personality disorder and impulsiveness were associated with the absence of a clear 24-hour periodicity in motor activity. Depressive mood and hopelessness were associated with a less regular bed-in time and a lower daytime activity. Platelet 5-HT as well as MAO correlated negatively with the amplitude of the circadian activity rhythm. Our results support the suggested link between suicidality, altered circadian activity and serotonergic function.

Adult

Effect of disease and drug treatment on blood serotonin and monoamine oxidase B activity in Parkinson's disease.

Serotonin (5-hydroxytryptamine, 5HT) content and monoamine oxidase (MAO) activity were determined in whole blood of patients with Parkinson's disease (PD) with and without drug treatment and compared with controls. From that comparison a significant reduction in platelet 5HT became apparent in PD. Selegiline, which was always used in combination with L-dopa, not only inhibited MAO activity, as expected, but it also appeared to induce an increase in 5HT content.

Adult

Analysis of phenprocoumon and its hydroxylated and conjugated metabolites in human urine by high-performance liquid chromatography after solid-phase extraction.

The anticoagulant phenprocoumon is mainly metabolized in humans to hydroxylated metabolites and their glucuronides. A method is described for the determination of phenprocoumon, 4'-hydroxyphenprocoumon, 6-hydroxyphenprocoumon, 7-hydroxyphenprocoumon, and their glucuronide and sulphate conjugates in human urine. Reversed-phase high-performance liquid chromatography is performed after selective extraction with disposable quaternary amine columns of untreated, and beta-glucuronidase- or sulphatase-treated urine samples. Urinary excretion data are presented for total, glucuronidated, sulphated and free phenprocoumon, 4'-hydroxyphenprocoumon, 6-hydroxyphenprocoumon and 7-hydroxyphenprocoumon in twelve patients after an average daily dosage of 1.3-4.2 mg phenprocoumon.

Adult

[Lithium].

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Bipolar Disorder

Assay of platelet monoamine oxidase in whole blood.

Monoamine oxidase (MAO; EC 1.4.3.4.) was measured in whole blood with kynuramine as the substrate. Optimal circumstances were determined. By use of selective inhibitors, gradient centrifugation, dilution of samples and removal of thrombocytes from whole blood it was shown that this assay of MAO in whole blood is in fact a determination of platelet MAO. No reversible endogenous inhibitors are present in the blood. Because preparation of platelet-rich plasma may lead to considerable losses of specific subpopulations with relatively low or high enzyme activities, the advantage of using whole blood is that the MAO activity is determined in the whole platelet population.

Blood Platelets

The effects of valproic acid on liver function.

To study a possible enzyme-inducing potency of valproic acid (VPA) in children, serum gamma-glutamyltranspeptidase (GGT) activity in serum and D-glucaric acid (GLA) excretion in urine were measured in 32 epileptic children who were on sodium valproate monotherapy (29.6 +/- 10.3 mg/kg/day). VPA did not affect GGT activity, but it selectively enhanced GLA excretion. To approach this phenomenon experimentally an attempt was made to induce a similar effect in animals. In guinea pigs it was possible to provoke a VPA induced rise in GLA excretion. In addition, vacuolisation of the cytoplasm of the hepatic parenchymal cells was observed. The question of the possible relationship between VPA hepatotoxicity and stimulation of GLA excretion remains to be answered.

Animals

Serum concentrations and enzyme induction in epileptic children treated with phenytoin and valproate.

In a group of 59 epileptic children treated with phenytoin (PHT) and valproate sodium (VPA), either alone or in combination, the following effects were studied: (1) the reciprocal effect on the serum levels of the two drugs, and (2) the enzyme-inducing effects of both drugs. VPA had no effect on PHT levels, but PHT significantly decreased VPA concentrations. PHT enhanced both gamma-glutamyltranspeptidase activity (gamma-GT) and D-glucaric acid excretion (GLA); these effects were potentiated by VPA. VPA alone did not affect gamma-GT, but significantly enhanced GLA.

Child

The appearance of erythrocyte membrane elevations. Effects of cooling rates.

Low cooling rates during the freezing procedure of normal human blood reveals red cell membrane elevations in freeze-etch electron microscopy. When high cooling rate is applied, these morphological changes are present, if the blood samples are quenched from 5 degrees C. The number of elevations is strongly reduced by low pH and glycerol. Elevations are not observed in ghosts. The formation of intramembrane particle aggregation is differently affected by many conditions.

Anticoagulants