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Biomedical subjects

N P Verhoeff

Publications and source records attributed to N P Verhoeff.

At least 37 records · Page 2Linked to original sources
PubMed1994

Stereotypy, schizophrenia and dopamine D2 receptor binding in the basal ganglia.

Animal models suggest a relationship between disturbed striatal dopaminergic function and stereotyped behaviour. Several studies show increased stereotypy in schizophrenic patients compared to normal controls. We investigated the performance of 12 antipsychotic-drug-free schizophrenic patients, and 15 healthy control subjects on a neuropsychological measure of stereotypy--the two-choice guessing task--and correlated this with in vivo striatal dopamine D2 receptor binding, as measured by 123I-iodobenzamide single photon emission tomography. Patients and controls did not differ with respect to the measures of stereotypy derived from the task. However, there was a significant correlation between one of these measures (RR Information) and the degree of striatal D2 receptor binding asymmetry in the patient group only. In view of research connecting striatal and frontal lesions with stereotypy in animals and cognitive inflexibility in humans, these data could suggest a similar disturbance underlying the phenomenon in schizophrenia.

Adolescent↗
PubMed1994

D2 dopamine receptor binding in the basal ganglia of antipsychotic-free schizophrenic patients. An 123I-IBZM single photon emission computerised tomography study.

We used SPECT to examine striatal D2 receptor binding in 20 antipsychotic-free DSM-III-R schizophrenic patients and 20 age- and sex-matched normal controls. Dynamic single-slice SPECT, at a slice chosen to include the basal ganglia, began immediately following intravenous injection of 185 MBq of 123I-IBZM. A semiquantitative approach was used to generate indices of specific D2 receptor binding in the basal ganglia. There was no overall elevation of D2 receptor binding between patients and controls. A male sex-specific left lateralised asymmetry of striatal D2 receptor binding was found in the patient group. Age-dependent decline of striatal D2 receptors was confirmed in controls, but not in patients. These results suggest that alterations in striatal D2 receptor distribution and density do occur in schizophrenia, and possibly reflect wider disruptions in prefrontal-striatal-limbic circuits.

Adolescent↗
PubMed1993

Imaging of dopamine D2 and somatostatin receptors in vivo using single-photon emission tomography in a patient with a TSH/PRL-producing pituitary macroadenoma.

A 28-year-old man with a thyroid stimulating hormone/prolactin (TSH/PRL)-secreting pituitary macroadenoma is discussed in relation to dopamine D2 and somatostatin receptor single-photon emission tomography (SPET). The patient presented with decreased vision in the left eye as a result of a temporal visual field defect and with mild hyperthyroidism. Medical therapy was tried. A test dose of both octreotide and bromocriptine resulted in an acute reduction in serum levels of TSH, alpha-subunits and PRL, whereas there was no response to TRIAC. Somatostatin and dopamine D2 receptors were present on the tumour as visualised by SPET with the ligands indium-111 diethylene triamine penta-acetic acid (DTPA)-octreotide (111In-SMS) and iodine-123 iodobenzamide (123I-IBZM), respectively. Therefore, treatment with octreotide 150 micrograms t.i.d. subcutaneously and bromocriptine 10 mg b.i.d. orally was given for > 12 and > 6 weeks, respectively. Following this treatment the visual defects disappeared, although tumour size, as measured by CT scanning, and serum TSH levels did not decrease. SPET with 111In-SMS and 123I-IBZM after therapy revealed no change or a possible increase in somatostatin receptor binding potential and a possible decrease in dopamine D2 receptor binding potential. The lack of long-term effects of the medical treatment is discussed. It is concluded that a high somatostatin and dopamine D2 receptor binding potential in vivo in a TSH/PRL-producing adenoma does not necessarily predict a successful outcome of medical treatment.

Administration, Oral↗
PubMed1993

Dosimetry of iodine-123 iomazenil in humans.

The distribution of the central benzodiazepine receptor specific ligand iodine-123 iomazenil was investigated in seven human adults from whole-body scans, blood samples and urine collected up to 24 h after injection. Using 12 source organs, the MIRD method was applied to calculate the absorbed radiation dose of the radioligand in various organs. The urinary bladder wall (0.15 mGy/MBq), lower large intestinal wall (0.071 mGy/MBq) testes (0.044 mGy/MBq) and upper large intestined wall (0.038 mGy/MBq) received the highest absorbed doses. The average effective dose equivalent of 123I-IBZM for adults was estimated to be 0.033 mSv/MBq.

Adult↗
PubMed1993

Dosimetry of iodine-123 iodobenzamide in healthy volunteers.

The distribution of the dopamine D2-receptor specific ligand iodine-123 (S)-(-)-2-hydroxy-3-iodo-6-methoxy-N[(1-ethyl-2- pyrrolidinyl)methyl]-benzamide (123I-IBZM) was investigated in human adults from whole-body scans, blood samples and urine collected up to 48 h after injection. Results from the present study performed in six healthy volunteers were combined with those of five volunteers from a previous study. Using the brain, liver, lungs and spleen as source organs, the MIRD method was applied to calculate the absorbed radiation dose of the radioligand in various organs. The thyroid (despite blockage), gallbladder wall, large intestinal walls and spleen received the highest absorbed doses. The average effective dose equivalent of 123I-IBZM for adults was estimated to be 0.034 mSv/MBq. The absorbed dose to the thyroid may be a limiting factor for 123I-IBZM studies in children.

Adult↗
PubMed1993

Antipsychotic medication, D2 dopamine receptor blockade and clinical response: a 123I IBZM SPET (single photon emission tomography) study.

The hypothesis that poor response to antipsychotic medication is due to inadequate occupancy of central D2 receptors was tested in vivo. We assessed striatal D2 dopamine receptor availability for binding with the specific ligand 123I IBZM by single photon emission tomography (SPET) in two groups of DSM-III-R diagnosed schizophrenic patients on typical antipsychotic medication, and a group of healthy controls (N = 20). Patients were characterized by clinical ratings as antipsychotic responders (N = 10) or non-responders (N = 8). Dynamic single slice SPET, at a slice chosen to include the basal ganglia, began immediately following intravenous injection of 185 MBq 123I IBZM. Semiquantitative analysis generated indices of D2 receptor availability for binding. There was no difference in striatal D2 receptor availability between the patient groups, both showing a similar degree of occupancy by antipsychotic medication compared to the control group. Thus, poor clinical response does not appear to be accounted for by differential blockade, or inadequate occupancy of striatal dopamine D2 receptors by antipsychotic medication.

Adult↗
PubMed1993

Dopamine D2-receptor imaging with 123I-iodobenzamide SPECT in migraine patients abusing ergotamine: does ergotamine cross the blood brain barrier?

Two migraine patients were studied by in vivo SPECT using the dopamine D2-receptor specific radioligand 123I-3-iodo-6-methoxybenzamide (123I-IBZM) during ergotamine abuse and after withdrawal. Results were compared with 15 healthy controls. Striatum/cerebellum and striatum/occipital cortex ratios of count rate density were calculated as a semiquantitative measurement for striatal dopamine D2-receptor binding potential. No differences were found in striatal uptake of 123I-IBZM between healthy controls and the patients when on or off ergotamine. Preliminary evidence suggests that ergotamine may not occupy striatal dopamine D2-receptors to a large extent and thus may not cross the blood brain barrier in large quantities.

Benzamides↗
PubMed1993

123I-SCH 23982 is not suitable for dopamine D1 receptor imaging in vivo in the human brain.

The tracer 123I-SCH 23982 was tested with regard to its ability to image dopamine D1 receptor in the human brain in vivo with single photon emission computed tomography (SPECT). The tracer did not reach equilibrium with regard to its binding to dopamine D1 receptors, presumably owing to fast metabolism to hydrophilic products and deiodination. It is concluded that 123I-SCH 23982 is not suitable for dopamine D1 receptor imaging with SPECT in the human brain.

Adult↗
PubMed1993

Quantification of central benzodiazepine receptor binding potential in the brain with 123I-iomazenil SPECT: technical and interobserver variability.

Factors contributing to the quantification of the central benzodiazepine receptor binding potential in vivo using 123I-iomazenil and single photon emission computed tomography (SPECT) were analysed in phantom studies and in volunteers. SPECT was performed with the SME810 multidetector system. The Hoffman three-dimensional brain phantom was used to investigate linearity and reproducibility of SPECT results using different 123I activity concentrations. Dynamic and multislice SPECT scans were performed in nine healthy volunteers between 0 and 270 min after injection of 110 MBq 123I-iomazenil. Displacement studies were performed in three volunteers using 1 mg flumazenil administered intravenously (i.v.) at 250 min postinjection (p.i.). Regions of interest (ROIs) over the cerebral cortex and various subcortical nuclei were either fixed areas based on a stereotaxic brain atlas, or manually drawn, based on 60% isocontour lines. Interobserver variability of the ROI data and ratios derived from those data were estimated for two independent observers. The brain phantom measurements showed linearity with respect to 123I concentration and good reproducibility. The interobserver study showed a reasonable interobserver reliability for the large fixed ROIs. The displacement study showed about 50% displacement in all ROIs. Concentrations of 123I-iomazenil in the brain can be measured reliably with the SME810. Large fixed ROIs based on a stereotaxic atlas may be used reliably for quantification. The level of 4 cm above the cantomeatal line does not provide a useful reference region with a very low central benzodiazepine receptor binding potential.

Adult↗
PubMed1993

Intracranial dissemination of a macroprolactinoma.

A patient with a macroprolactinoma and extrasellar extension was treated by incomplete transfrontal surgery, external irradiation and additional bromocriptine (Br) treatment. After 4 years, partial bromocriptine resistance developed (a rare occurrence) together with the appearance of intracranial metastases. 123I-Iodobenzamide was helpful in evaluating the dopamine D2 receptor status of the metastatic tumour both in vivo using single-photon emission computed tomography (SPECT) and in vitro. Prolactin release by the cultured metastatic tumour cells was more potently inhibited by CV 205-502 than by bromocriptine. The patient, treated by surgery, irradiation and CV 205-502, developed a ptosis of the left eye and a transient psychiatric delusional state, the latter probably an effect of the dopamine agonist. As the right frontal metastasis was markedly positive on SPECT with 111In-SMS, somatostatin treatment was added to the CV 205-502.

Aminoquinolines↗
PubMed1993

Estimation of dopamine D2 receptor binding potential in the striatum with iodine-123-IBZM SPECT: technical and interobserver variability.

Factors contributing to the quantification of the striatal dopamine D2 receptor binding potential in vivo using 123I-iodobenzamide (123I-IBZM) and SPECT were analyzed in phantom studies, healthy volunteers and in patients with the parkinsonian syndrome. A cylindrical brain phantom based on a stereotactic brain atlas was constructed with independently fillable compartments representing two striata (ST), cerebellum (CB) and background. Clinical 123I-IBZM SPECT studies were performed on 15 healthy volunteers and on 28 patients with parkinsonian syndrome. Interobserver variability of region of interest (ROI) selection and count ratios were estimated by two independent observers. ROIs for the striatum were either fixed, based on a stereotactic brain atlas, or drawn manually, based on 70% isocontour lines. Reference regions were either the cerebellum (isocontour ROIs) or the occipital cortex (occiptal cortex; fixed ROIs). The brain phantom measurements showed linearity with respect to radioactivity concentration, good reproducibility and good contrast recovery. The interobserver study showed that the striatum-to-occiptal cortex ratio with fixed ROIs for the striatum, as an estimate for striatal D2 receptor binding potential, resulted in a means of separating patients with normal receptor activity from those with decreased striatal dopamine D2 receptor activity.

Adolescent↗
PubMed1992

Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia.

According to the dopamine hypothesis of schizophrenia, D2 receptor blockade is essential for a drug to have antipsychotic potency, and antipsychotic potency and D2 blockade are linearly related in vitro. To test this assumption in vivo, we have compared clinical response with central D2 dopamine receptor availability measured by 123I-iodobenzamide single photon emission tomography in two groups of schizophrenic patients. 6 patients were on typical antipsychotic drugs and 10 were on the atypical antipsychotic clozapine, including 2 patients from the first group. The patients on typical antipsychotics showed poor therapeutic response despite D2 receptor blockade. Significant clinical improvement occurred in all patients on clozapine, but at a lower level of D2 blockade by the drug. These findings suggest a more complex relation between D2 blockade and clinical efficacy than was previously thought.

Adult↗
PubMed1992

Memory complaints, memory disorders and focus localization in patients with partial epilepsy.

Our study aimed at analysing effects of epileptic foci on memory function in patients with partial epilepsy. Twenty-eight patients with spontaneous memory complaints and psychometrically established memory disorders were assessed by 21-channel electroencephalography recorded both during cognitive testing and during 99mTc-HMPAO single photon emission computed tomography (SPECT). Computed tomography (CT) was performed on the same day. None of the epilepsy-related factors (seizure type, seizure frequency, type of epilepsy, age at onset of the seizures, type of antiepileptic treatment) could be related directly to severity or type of memory impairment (classified into the categories 'global', 'verbal' and 'non-verbal'). Remarkably, this study found no significant relationship between EEG focus localization and severity of measured memory impairment. Most areas with hypoperfusion on the SPECT were found in the group with global (severe) amnesia, typically with a right frontal localization. Abnormalities on CT were predominantly found in the same group, however, with a right-sided parietal localization. An unanticipated finding was that the majority of temporal CT and SPECT lesions were found in the group with relatively better memory performance.

Adult↗