Biomedical subjects

J Passchier

Publications and source records attributed to J Passchier.

At least 19 recordsLinked to original sources

PubMed2001

Quantifying drug-related 5-HT1A receptor occupancy with.

RATIONALE: There is an increased interest in measuring the interaction of new or established drugs with their targets, in order to gain a better understanding of their mechanisms of action. PET can provide this information if an appropriate radioligand is available. [18F]MPPF (4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[18F]fluorobenzamido]ethylpiperazine) is a selective radioligand for serotonin 5-HT1A receptors. We have established that the binding potential (BP=Bmax/KD) of [18F]MPPF for cerebral 5-HT1A receptors can be assessed in human brain without arterial sampling. OBJECTIVES: The aim of this study was to assess if 5-HT1A receptor occupancy can be measured through calculation of a drug-related decrease in BP with [18F]MPPF and PET. METHODS: Six volunteers were scanned twice using a Siemens Exact HR+ camera following injection of 70+/-18 MBq [18F]MPPF (baseline and medicated conditions). Before the second scan, volunteers orally received either 3x10 mg pindolol at T=-15.5 h, T=-6.5 h, and T=-1.5 h (n=3) or 10 mg buspirone in a single dose at T=-1.5 h (n=3). Binding potentials were calculated using the simplified reference tissue model with the cerebellum as reference. RESULTS: Administration of 30 mg pindolol led to a significant reduction in [18F]MPPF binding potential of 42+/-17%. In contrast, no significant reduction of [18F]MPPF binding potential was observed following administration of buspirone (5+/-17%). CONCLUSIONS: These results show that [18F]MPPF can be used for measurement of drug-related 5-HT1A receptor occupancy and may be of particular interest in determining the 5-HT1A receptor interaction of new or established drugs in phase 1 and early phase 2 drug trials. Apparently, the 5-HT1A partial agonist buspirone is already clinically effective at low levels of 5-HT1A receptor occupancy.

Adrenergic beta-Antagonists↗

PubMed2001

Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system.

The 5-HT1A subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy. Here, we review the radioligands which are available for visualisation and quantification of this important neuroreceptor in the human brain, using positron emission tomography (PET) or single-photon emission tomography (SPET). More than 20 compounds have been labelled with carbon-11 (half-life 20 min), fluorine-18 (half-life 109.8 min) or iodine-123 (half-life 13.2 h): structural analogues of the agonist, 8-OH-DPAT, structural analogues of the antagonist, WAY 100635, and apomorphines. The most successful radioligands thus far are [carbonyl-11C] WAY-100635 (WAY), [carbonyl-11C]desmethyl-WAY-100635 (DWAY), p-[18F]MPPF and [11C]robalzotan (NAD-299). The high-affinity ligands WAY and DWAY produce excellent images of 5-HT1A receptor distribution in the brain (even the raphe nuclei are visualised), but they cannot be distributed to remote facilities and they probably cannot be used to measure changes in endogenous serotonin. Binding of the moderate-affinity ligands MPPF and NAD-299 may be more sensitive to serotonin competition and MPPF can be distributed to PET centres within a flying distance of a few hours. Future research should be directed towards: (a) improvement of the metabolic stability in primates; (b) development of a fluorinated radioligand which can be produced in large quantities and (c) production of a radioiodinated or technetium-labelled ligand for SPET.

Central Nervous System↗

PubMed2001

The association between physiological and behavioral pain measures in 0- to 3-year-old infants after major surgery.

To estimate the association between behavioral and physiological pain measures and to identify determinants predicting the level of association, the COMFORT 'behavior' scale, heart rate (HR), mean arterial pressure (MAP), and the variability of HR and MAP (HRV and MAPV) were assessed every 3 hours after major abdominal or thoracic surgery. Subjects were 204 infants aged 0-3 years. The within-subject correlations, using the repeated measures, were 0.37, 0.44, 0.48, and 0.49 for COMFORT 'behavior' with HRV, HR, MAP, and MAPV, respectively. Neonates had lower behavior-physiology correlations than the older infants, due to low pain scores. Pain characteristics significantly predicted the COMFORT 'behavior'-HR/MAP correlations, suggesting that the behavior-physiology correlations increase with increasing pain. The behavior-physiology correlations were not greatly affected by physical condition. These data demonstrate large interindividual differences in behavior-physiology correlations after major surgery in 0- to 3-year-old infants. These differences should be further explored in future research.

Abdomen↗

PubMed2001

Quality of life in adolescents with chronic pain in the head or at other locations.

The differences in quality of life and school absence were studied in one hundred adolescents from the open population who had reported chronic headache or chronic, physically unexplained, pain at other locations. The adolescents kept a 3-week diary about their pain and completed a quality of life questionnaire. Of all chronic pain sufferers in this study, it was the adolescents with headache who showed the least frequent pain, but they reported the poorest quality of life and the largest school absence due to their pain. Adolescents with headache or adolescents with back pain showed the highest negative correlations between pain parameters and quality of life. Headache sufferers showed highly negative relationships between pain parameters and most quality of life domains (median r = -0.46), and only in headache sufferers did this involve both intensity and frequency of pain. Qualitative studies are needed to reveal the background to these differences.

Absenteeism↗

PubMed2001

Interictal and postictal contingent negative variation in migraine without aura.

Cortical hyperexcitability is thought to explain the more enhanced contingent negative variation (CNV) amplitudes and impaired CNV habituation that have been found during the interictal period in migraine without aura. These CNV characteristics have been shown to normalize to the level of healthy controls during an attack. This study aimed to replicate the interictal findings, and additionally examine whether migraineurs show reduced CNV amplitudes during the postattack period. Of 12 patients with migraine without aura and their sex- and age-matched healthy controls, CNV characteristics were recorded once in an interictal period, once during the postattack period within 30 hours after an attack that was treated with sumatriptan, and once after an attack that was treated with habitual nonvasoactive medication (counterbalanced). The present results did not confirm the enhanced CNV early and late wave amplitudes or impaired habituation, and cortical hyperexcitability that have previously been reported in the interictal period in patients with migraine without aura. During the postattack period, a decrease in CNV early and late amplitudes was found but only after sumatriptan use. This reduction in CNV amplitudes was most prominent over the frontal cortex and could reflect cortical hypoexcitability, possibly related to a suppression of central catecholaminergic activity by sumatriptan.

Adult↗

PubMed2001

Prevalence and characteristics of headache in Dutch schoolchildren.

The aim of this study was to determine whether there has been an increase in headache prevalence in Dutch children and to compare headache characteristics of children with low, medium and high headache severity.A sample of 2358 schoolchildren between the ages of 10 and 17 years filled out Waters' Headache Questionnaire and the Paediatric Pain Assessment Tool. Results showed that 21% of the boys and 26% of the girls at elementary school, and 14% of the boys and 28% of the girls at high school reported weekly headaches. When compared to figures from a previous study in the Netherlands published in 1985, the prevalence of weekly headaches in 10-17-year-olds has increased by 6%. In boys at elementary school, the prevalence of headaches with a frequency of a few times a week has doubled. Children with low, medium and high headache severity differed with respect to all headache characteristics, i.e. pain quality, accompanying symptoms, warning signals, location, onset, impact of headache, family occurrence, perceived cause, medical consultation, and school absence.

Absenteeism↗

PubMed2001

On the quantification of [18F]MPPF binding to 5-HT1A receptors in the human brain.

UNLABELLED: Previous studies have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperazine ([(18)F]MPPF) binds with high selectivity to serotonin (5-HT(1A)) receptors in man. However, in these studies, the calculation of the binding potential (BP, which equals receptor density divided by equilibrium dissociation constant) used a metabolite-corrected arterial input. The aim of this study was to determine whether metabolite correction and arterial sampling are essential for the assessment of BP. METHODS: Five analytic methods using full datasets obtained from 6 healthy volunteers were compared. In addition, the clinical applicability of these methods was appraised. Three methods were based on Logan analysis of the dynamic PET data using metabolite-corrected and uncorrected arterial plasma input and cerebellar input. The other 2 methods consisted of a simplified reference tissue model and standard compartmental modeling. RESULTS: A high correlation was found between BP calculated with Logan analysis using the metabolite-corrected plasma input (used as the reference method for this study) and Logan analysis using either the uncorrected arterial plasma input (r(2) = 0.95, slope = 0.85) or cerebellar input (r(2) = 0.98, slope = 0.91). A high correlation was also found between our reference method and the simplified reference tissue model (r(2) = 0.94, slope = 0.92). In contrast, a poor correlation was observed between our reference method and the standard compartmental model (r(2) = 0.45, slope = 1.59). CONCLUSION: These results indicate that neither metabolite analysis nor arterial sampling is necessary for clinical evaluation of BP in the human brain with [(18)F]MPPF. Both the Logan analysis method with cerebellar input and the simplified reference tissue method can be applied clinically.

Adult↗

PubMed2000

Influence of P-glycoprotein on brain uptake of [18F]MPPF in rats.

The aim of this study was to determine if the brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[18F]fluorobenzamido ]ethylpiperazine ([18F]MPPF), a radioligand for the imaging of 5-HT1A receptors, is influenced by the action of P-glycoprotein. Anesthetized male Wistar rats were injected i.v. with the 5-HT1A receptor antagonist [18F]MPPF (2 MBq, S.A.>110 TBq/mmol) after treatment with saline (controls) or with the 5-HT1A receptor antagonist 1-(2'-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190) (2.5 mg/kg i.v.). After 60 min, the animals were sacrificed and 13 areas of the brain were dissected for ex vivo gamma counting. The regional distribution of radioactivity was also assessed in brain slices using a storage phosphor system. Modulation of P-glycoprotein was achieved by injection of cyclosporin A (50 mg/kg) 30 min prior to injection of [18F]MPPF.The distribution of 18F-derived radioactivity corresponded to regional 5-HT1A receptor density as known from autoradiography. Modulation of P-glycoprotein with cyclosporin A caused a 5- to 10-fold increase in the uptake of [18F]MPPF. Tissue/cerebellum ratios in the brain correlated with receptor densities determined by in vitro autoradiography. Measurements of plasma radioactivity showed that the increased brain uptake of [18F]MPPF is partially due to a rise in ligand delivery after treatment with cyclosporin A (area under the curve, AUC, increased by a factor of 1.8). Biodistribution experiments in wild type and mdr1a(-/-) knockout mice confirmed that [18F]MPPF is a substrate for P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Towards an objective quantitative assessment of daily functioning in migraine: a feasibility study.

Migraine is a chronic disabling disorder, with migraine episodes significantly reducing quality of life and leading to impaired functioning (physically, socially, emotionally) both at home and at work. We explored whether ambulatory accelerometry can be used as an objective method to quantify the behavioral aspects of migraine-related disability. Four body mounted uni-axial piezo-resistive accelerometers were used to quantify the time spent in different body postures (lying, sitting, standing), physical activities (walking, cycling) and a general index of body motility during eight migraine attacks and subsequent recovery periods of six patients in their habitual environment. The migraine attacks and recovery periods could be monitored after about 1 h, which was the time required for the investigator to travel to the patient and for the sensors to be attached. In order to quantify the influence of a migraine episode on daily activities, we also performed measurements during a headache-free baseline period of the same patients. Overall, the procedures functioned well, indicating that ambulatory accelerometry measurements before, during and after a migraine attack are feasible to perform. Furthermore, our quantitative data revealed that migraine always influenced behavior by reducing overall body motility and that, dependent upon the severity of the attack, the effectiveness of acute treatment and the time of day, the time spent in various body positions, dynamic activities, and the number of postural transitions were affected. This feasibility study showed that ambulatory accelerometry can provide the objective behavioral effect parameters for the evaluation of migraine and its treatment on daily functioning in the habitual environment of migraine patients.

Activities of Daily Living↗

PubMed2000

The reliability and validity of the COMFORT scale as a postoperative pain instrument in 0 to 3-year-old infants.

The aim of this study was to test the reliability and validity of the COMFORT scale as a postoperative pain instrument for children aged 0-3 years. Subjects were 158 neonates and toddlers after major abdominal or thoracic surgery. Trained nurses rated the children's pain at 3, 6 and 9 h postoperative on the Pediatric Surgical Intensive Care Unit using the COMFORT and a VAS for pain. Interrater reliability of the COMFORT items proved to be good (Kappa 0.63-0.93) for all items with the exception of the item 'Respiratory response', which was moderate (Kappa 0.54). LISREL analyses showed that the structure of the COMFORT data was best represented by three latent variables: COMFORT 'behaviour' with loadings from the behavioural items (Alertness, Calmness, Respiratory response/Crying, Physical movement, Muscle tone and Facial tension) and separate latent variables for 'Heart rate baseline' (HR) and 'Mean arterial blood pressure baseline' (MAP). Factor loadings of the items were invariant across time, indicating stability of the structure. The latent variables COMFORT 'behaviour' and VAS pain were highly interrelated indicating congruent validity. Stability of COMFORT 'behaviour' and VAS pain was moderate which might be due to varying painful episodes in this sample. HR and MAP, although stable across time, were weakly related to VAS pain and COMFORT 'behaviour'. These findings support the use of the COMFORT 'behaviour' scale to assess postoperative pain in neonates and infants.

Blood Pressure↗

PubMed2000

Quantitative imaging of 5-HT(1A) receptor binding in healthy volunteers with [(18)f]p-MPPF.

Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido+ ++] ethylpiperazine ([(18)F]p-MPPF) can be used for 5-hydroxytryptamine(1A) (5-HT(1A)) receptor imaging. The aim of this study was to develop a method for the quantitative imaging of 5-HT(1A) receptors in healthy volunteers with [(18)F]p-MPPF. After injection of [(18)F]p-MPPF radioactivity was rapidly taken up in the brain, with the highest accumulation in the medial temporal cortex. Low levels of radioactivity were found in cerebellum and basal ganglia. Plasma clearance and metabolism of [(18)F]p-MPPF resulted in only about 1% of the radioactivity in plasma as parent radioligand after 10 min. Using a linear graphical method (Logan-Patlak), binding potentials were calculated in several brain areas. A good correlation (r = 0.95) was found between the obtained binding potentials and literature values for 5-HT(1A) receptor densities. A good correlation (r = 0.96) was also found between the body weight-corrected region/cerebellum ratios and the respective binding potentials. Moreover, a blocking experiment with pindolol (n = 3) showed a decrease of 40% in the region/cerebellum ratios of the target areas. Compared to those of [carbonyl-(11)C]WAY-100635, the binding potentials were four to six times lower, indicating that [(18)F]p-MPPF has a lower in vivo affinity for 5-HT(1A) receptors. In conclusion, [(18)F]p-MPPF can be used for the quantitative analysis of 5-HT(1A) receptor distribution in human brain.

Adult↗

PubMed2000

Recurrent headache, coping, and quality of life in children: a review.

OBJECTIVES: To clarify the concepts of coping with pain and quality of life (QoL) and to present a literature review of the strategies that children with recurrent headaches use to cope with their pain, the impact of recurrent headaches on children's QoL, and the influence of personal and situational variables on headache, coping, and QoL in children. METHODS: The literature search encompassed published articles that were found by means of a CD-ROM search of MEDLINE (1966 to December 1998) and PsycLIT (1974 to December 1998) and the snowball method. RESULTS: In pediatric headache research, only three studies have been found in which children report the use of various coping strategies, and only two studies considered QoL. Demographic factors and psychological variables such as depression, anger, and anxiety influence headache prevalence. The impact of headache-related variables such as headache type, severity, perceived cause, and prior experience on QoL has only been studied in adults. CONCLUSIONS: More research on coping and QoL is needed in pediatric headache. The conceptual model that is presented in this article may serve as a guide.

Adaptation, Psychological↗

PubMed2000

Chronic pain among children and adolescents: physician consultation and medication use.

OBJECTIVE: The goal of this study was to assess physician consultation and use of medication in Dutch children and adolescents (0-18 years old) having chronic pain in relation to sociodemographic factors and pain characteristics. DESIGN: This was a population-based cross-sectional survey. A questionnaire was either mailed to the participants' parents or distributed at school, and it was filled out by the parents (for children aged 0-7 years) or by the participant (for children and adolescents aged 8-18 years). SETTING: The study was conducted in the Rotterdam area. PATIENTS: Participants included a random sample of 1,300 children aged 0 to 3 years taken from the register of population. In addition, 41 schools were selected to obtain a representative sample of 5,336 children and adolescents aged 4 to 18 years. OUTCOME MEASURES: Reported physician consultation and medication use were assessed. RESULTS: Of the 6,636 children and adolescents surveyed, 5,424 (82%) responded. A total of 1,358 respondents (25%) reported chronic pain. Of these, 57% had consulted a physician and 39% had used medication for the pain. Respondents with earache, more intense pain, and more frequent pain and those attending lower vocational training programs were more likely to consult a physician for the pain than the average respondent. Respondents with earache, sore throat, headache, more intense pain, and multiple pain; children aged 0 to 3 years; and girls were more likely to use medication for the pain. Logistic regression analyses showed that for physician consultation, the most significant predictive factors were the intensity of pain, age, and earache as well as the level of education for respondents aged 12 to 16 years. The use of medication was predicted by earache, headache, limb pain, intensity of pain, and age. CONCLUSIONS: Chronic pain is a common complaint in children and adolescents, frequently resulting in consultation of a physician and medication use. Regarding physician consultation, children and adolescents with a lower educational level seem to be a group at risk.

Adolescent↗

PubMed2000

In vivo delineation of 5-HT1A receptors in human brain with [18F]MPPF.

UNLABELLED: Serotonin-1A (5-hydroxytryptamine-1A [5-HT1A]) receptors have been reported to play an important role in the pathophysiology of a variety of psychiatric and neurodegenerative disorders. Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2'-pyridinyl)-p-[18F]fluorobenzamido ]ethylpiperazine ([18F]MPPF) may be suitable for 5-HT1A receptor imaging in humans. The aim of this study was to determine if [18F]MPPF can be used for the quantitative analysis of 5-HT1A receptor densities in brain regions of healthy human volunteers. METHODS: [15O]H2O perfusion scanning was performed before intravenous injection of [18F]MPPF to obtain anatomic information. Cerebral radioactivity was monitored using a PET camera. Plasma metabolites of [18F]MPPF were determined by high-performance liquid chromatography. Binding potentials were calculated using the metabolite-corrected arterial input function and a linear graphic method (Logan-Patlak analysis). RESULTS: The highest levels of radioactivity were observed in the medial temporal cortex, especially in the hippocampal area. In contrast, the cerebellum and basal ganglia showed low uptake of 18F, in accordance with known 5-HT1A receptor distribution. The calculated binding potentials correlated well with literature values for 5-HT1A receptor densities. The binding potentials for [18F]MPPF were 4-6 times lower than those that have been reported for [carbonyl-1C]-(N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyrid yl) cyclohexane-carboxamide (WAY 100635), indicating that [18F]MPPF has a lower in vivo affinity for 5-HT1A receptors. CONCLUSION: These results confirm that [18F]MPPF can be used for the quantitative analysis of 5-HT1A receptor distribution in the living human brain. The rapid dissociation from the receptor makes this ligand a possible candidate to monitor changes in endogenous serotonin levels.

Adult↗

PubMed1999

Modification in Quetelet index five months after myocardial infarction: relevance of biographic and personality characteristics.

BACKGROUND: Obesity can be considered as a risk factor for (re-)occurrence of coronary heart disease. METHODS: The relationship between modification in quetelet index and personality characteristics was assessed in 166 survivors of a first myocardial infarction (MI). Quetelet index (weight/(height)2) was calculated a few days after first MI and again 5 months later. A multiple regression analysis was executed, with the quetelet index after 5 months as dependent variable and adjustment for gender, age, and quetelet index at baseline. RESULTS: It was found that strong feelings of vital exhaustion and lack of tension significantly contributed to the prediction of increased quetelet index 5 months after a first MI. CONCLUSIONS: It is recommended that individually tailored interventions be used based on these personality characteristics to accomplish body weight reduction in MI patients.

Anxiety↗

PubMed1999

A structural modeling analysis of anxiety and depression in patients undergoing coronary artery bypass graft surgery: a model generating approach.

The present study is a longitudinal study designed to explore structural relationships between anxiety, depression, personality, and background factors (e.g., gender, age, and complicated medical characteristics) in patients undergoing coronary artery bypass graft (CABG) surgery. At two timepoints before and two after CABG, 217 patients completed self-report questionnaires. To explore structural relationships, the structural equation modeling (SEM) method was applied. Using the model-generating approach, a model was developed, providing a good fit. The structural relationships revealed, in particular, the key position of neuroticism, which was related to both pre- and postoperative anxiety and depression. Relationships between anxiety and depression over time, both intra- and interrelationships, were relatively weak. Relationships between anxiety and depression at the same points in time were relatively strong, with preoperative depression leading to preoperative anxiety, and postoperative anxiety leading to postoperative depression. To provide a useful framework for development of intervention strategies, further research is needed to evaluate the plausibility of the final structural model.

Adult↗

PubMed1999

Interictal and postictal cognitive changes in migraine.

The question whether symptom-free migraine patients show cognitive impairments compared to matched control subjects is addressed, and also whether migraine patients show transient cognitive impairments induced by an attack. The Neuropsychological Evaluation System (NES2) was administered once in an interictal period and twice within 30 h after different migraine attacks. Since cognitive impairments could be related to attack duration or severity, cognitive performance was compared during a postictal period after sumatriptan use and during a postictal period after habitual nonvasoactive medication use. Twenty migraineurs without aura, 10 migraineurs with aura, and 30 matched headache-free controls participated in the study. During a headache-free period, migraineurs without aura responded as quickly as controls, while migraineurs with aura were slower than controls during all tasks specifically requiring selective attention. These effects were not aggravated by a preceding migraine attack, irrespective of medication use and attack duration.

Adult↗

PubMed1999

Personality traits and psychological reactions to mental stress of female migraine patients.

The purpose of this study was (i) to compare a range of stress-related personality traits, including defense and coping mechanisms, of migraine patients (n = 23) with those of tension headache patients (n = 18) and dermatologically afflicted, but otherwise healthy, controls (n = 22), and (ii) to compare their state anxiety and other moods before, during, and after the presentation of a psychological stressor (mental arithmetic). For all three groups, mental arithmetic induced a significant increase in state anxiety and mood disturbance, followed by a subsequent decrease during recovery. Migraine patients were not found to have a higher disposition for anxiety, depression, or rigidity than tension headache patients or controls. Between the headache groups no differences in the use of defense and coping mechanisms were found. Compared to the control group, however, both migraine patients and tension headache patients were more inclined to use internally focused defense mechanisms and less inclined to seek social support when confronted with a problem. The psychological reaction of migraine patients to mental stress hardly differed from tension headache and control subjects. Compared to the control subjects, however, both groups of headache patients exhibited a diminished recovery from feelings of vigour, depression, and fatigue due to the stress induced. It is suggested that this distinct psychological reaction to stress of headache patients versus healthy control subjects is related to the more internally focused defense style of the headache sufferers. Thus, in contrast to previous results, this study does not present evidence of a migraine personality. It suggests the development of specific personality characteristics as a consequence of suffering from episodic headache.

Adaptation, Psychological↗