Developing-world research ethics.
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Clinical Trials as Topic↗
Biomedical subjects
D Wikler
Publications and source records attributed to D Wikler.
Statistical parametric mapping of regional glucose metabolism in mesial temporal lobe epilepsy.
We investigated statistical parametric mapping (SPM) use for positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) data analysis in mesial temporal lobe epilepsy. The study involved 14 patients with temporal lobe epilepsy ultimately treated by anterior temporal lobectomy. Surgical outcome in terms of seizure control was favorable in 12 patients. Two different SPM approaches were designed to analyze each FDG-PET scan: a direct comparison with a control group (n = 27) and a search for significant interhemispheric asymmetry considering the asymmetry existing in the control group. Statistical inference was performed, first, without correction for multiple comparisons (making the hypothesis of temporal hypometabolism) and, second, after correction for multiple comparisons. Search for temporal interhemispheric asymmetry under the hypothesis of temporal hypometabolism was the most reliable SPM approach: hypometabolism was identified on the side chosen for resection in most cases (sensitivity, 71%; specificity, 100%) and was predictive of favorable postsurgical outcome in 90% of the patients. There was no false-positive result within the control group using this approach. After correction for multiple comparisons, SPM also identified in some patients temporal hypermetabolic areas as well as extratemporal cortical and subcortical hypometabolic areas on the side of resection but also on the contralateral side. In a further step, SPM was used for a group analysis of patients with favorable outcome after reversing scans when needed to set an identical lateralization in all patients. This analysis identified multiple ipsilateral temporal and extratemporal hypometabolic regions; when temporal metabolic changes were specifically assessed, the contralateral mesiotemporal region was found hypermetabolic, possibly as a manifestation of compensatory mechanisms in the presence of a unilateral epileptogenic lesion.
Adolescent↗
Early alterations of myocardial blood flow reserve in heart transplant recipients with angiographically normal coronary arteries.
BACKGROUND: The evaluation of the coronary reserve provides valuable information on the status of coronary vessels. Therefore, we studied with positron emission tomography (PET) and 13N-ammonia the myocardial blood flow (MBF) reserve in heart transplant recipients free of allograft rejection and with angiographically normal coronary arteries early after heart transplantation (HTx). The MBF reserve was calculated as the ratio between MBF after dipyridamole injection and basal MBF normalized for the rate-pressure product. METHODS: Patients were studied within 3 months (group A, n = 12) or more than 9 months (group B, n = 12) after HTx. Five patients have been studied both during the early and late period after HTx. Results were compared to those obtained in 7 normal volunteers (NL). RESULTS: Group A recipients had a significantly lower dipyridamole MBF (in ml/min/100 gr of tissue) than that of group B recipients (142+/-34 vs 195+/-59, p<0.05). This resulted in a significant decrease in MBF reserve early after HTx (group A: 1.82+/- 0.33) and a restoration to normal values thereafter (group B: 2.52+/- 0.53 vs NL: 2.62+/-0.51, p = ns). Separate analysis of 5 patients studied twice is consistent with these results. CONCLUSION: This study shows that in heart transplant recipients free of allograft rejection and with normal coronary angiography, MBF reserve is impaired early after HTx. Restoration within one year suggests that this abnormality does not represent an early stage of cardiac allograft vasculopathy.
Adult↗
Combined magnetic resonance imaging- and positron emission tomography-guided stereotactic biopsy in brainstem mass lesions: diagnostic yield in a series of 30 patients.
OBJECT: In the management of brainstem lesions, the place of stereotactic biopsy sampling remains debatable. The authors compared the results of magnetic resonance (MR) imaging, positron emission tomography (PET) scanning, and histological studies obtained in 30 patients who underwent MR imaging- and PET-guided stereotactic biopsy procedures for a brainstem mass lesion. METHODS: Between July 1991 and December 1998, 30 patients harboring brainstem mass lesions underwent a stereotactic procedure in which combined MR imaging and PET scanning guidance were used. Positron emission tomography scanning was performed using [18F]fluorodeoxyglucose in 16 patients, methionine in two patients, and both tracers in 12 patients. Definite diagnosis was established on histological examination of the biopsy samples. Interpretation of MR imaging findings only or PET findings only was in agreement with the histological diagnosis in 63% and 73% of cases, respectively. Magnetic resonance imaging and PET findings were concordant in 19 of the 30 cases; in those cases, imaging data correlated with histological findings in 79%. Treatment based on information derived from MR imaging was concordant with therapy based on histological findings in only 17 patients (57%). Combining MR imaging and PET scanning data, the concordance between the neuroimaging-based treatment and treatments based on histological findings increased to 19 patients (63%). In seven patients who underwent biopsy procedures with one PET-defined and one MR imaging-defined trajectory, at histological examination the PET-guided samples were more representative of the tumor's nature and grade than the MR imaging-guided samples in four cases (57%). In 18 patients PET scanning was used to define a biopsy target and provided a diagnostic yield in 100% of the cases. CONCLUSIONS: Although the use of combined PET and MR imaging improves radiological interpretation of a mass lesion in the brainstem, it does not accurately replace histological diagnosis that is provided by a stereotactically obtained biopsy sample. Combining information provided by MR imaging and PET scanning in stereotactic conditions improves the accuracy of targeting and the diagnostic yield of the biopsy sample; an MR imaging- and PET-guided stereotactic biopsy procedure is a safe and efficient modality for the management of mass lesions of the brainstem.
Adolescent↗
Can we learn from eugenics?
Eugenics casts a long shadow over contemporary genetics. Any measure, whether in clinical genetics or biotechnology, which is suspected of eugenic intent is likely to be opposed on that ground. Yet there is little consensus on what this word signifies, and often only a remote connection to the very complex set of social movements which took that name. After a brief historical summary of eugenics, this essay attempts to locate any wrongs inherent in eugenic doctrines. Four candidates are examined and rejected. The moral challenge posed by eugenics for genetics in our own time, I argue, is to achieve social justice.
Cultural Diversity↗
[Imaging of cancer using positron emission tomography].
Positron emission tomography (PET) is a method making use of short half-life radioactive compounds which allow imaging and quantification of functional and metabolic data at the level of multiple organs. This method has been initially oriented towards neurological and cardiological applications but gets now a more widespread use in oncology. This recent development has been made possible thanks to methodological progresses allowing "whole body" imaging and thanks to the use of a practical tracer, the 2-[18 F]fluoro-2-deoxy-D-glucose (FDG). The uptake of this tracer is enhanced in diverse cancer tissues. Recent studies has clarified the biological processes which lead to this enhanced uptake of FDG in cancers. This new insight allows a rational and helpful usage of PET in diverse aspects of clinical oncology: diagnosis of lesion, staging, follow-up of patients and treatment evaluation.
Fluorodeoxyglucose F18↗
Asymmetry of basal ganglia glucose metabolism and dopa responsiveness in parkinsonism.
We investigated, by positron emission tomography (PET) with [18F]fluoro-2-deoxy-d-glucose (FDG) (FDG-PET), brain glucose metabolism in 19 patients with parkinsonian features. We compared local pattern of FDG uptake and asymmetry indexes in patients with therapeutic response to levodopa (L-dopa) (group 1, presumed Parkinson's disease, n = 9) and patients without L-dopa therapeutic response (group 2, presumed striatonigral degeneration, n = 10). Limb dystonia was present in 11% of patients in group 1 and in 40% of patients in group 2. Asymmetry in basal ganglia metabolism was distributed differently in the two groups (analysis of variance, p < 0.04). In superior and inferior putamen, superior and middle caudate, ventral striatum, and inferior thalamus, relative reduction in metabolism on the side contralateral to predominant parkinsonian signs was associated with L-dopa unresponsiveness. On the contrary, in middle caudate, ventral striatum, and inferior thalamus, a relative increase in metabolism on the side contralateral to the predominant side, parkinsonian signs were found in L-dopa-responsive patients. Our FDG-PET study using simple statistical procedures demonstrates inverse asymmetry of basal ganglia glucose metabolism in parkinsonian patients grouped on the sole basis of L-dopa responsiveness.
Adult↗
Regional changes in glucose metabolism during brain development from the age of 6 years.
Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) studies of 42 subjects ages 6 to 38 years were analyzed using statistical parametric mapping to identify age-related changes in regional distribution of glucose metabolism adjusted for global activity. Whereas adults were normal volunteers, children had idiopathic epilepsy. We studied polynomial expansions of age to identify nonlinear effects and found that adjusted glucose metabolism varied very significantly in the thalamus and the anterior cingulate cortex and to a lesser degree in the basal ganglia, the mesencephalon, and the insular, posterior cingulate, frontal, and postcentral cortices. Regression plots slowed that the best fit was not linear: adjusted glucose metabolism increased mainly before the age of 25 years and then remained relatively stable. Effects persisted when anti-epileptic drug intake and sleep during the FDG uptake were considered as confounding covariates. To determine if the metabolic changes observed were not due to the epileptic condition of the children, PET data obtained in adults with temporal lobe epilepsy were compared with those in our group of normal adult subjects, resulting in the absence of mapping in the age-related regions. This study suggests that brain maturation from the age of 6 years gives rise to a relative increase of synaptic activities in the thalamus, possibly as a consequence of improved corticothalamic connections. Increased metabolic activity in the anterior cingulate cortex is probably related to these thalamic changes and suggests that the limbic system is involved in the processes of brain maturation.
Adolescent↗
Cerebral glucose metabolism and centrotemporal spikes.
The pathophysiology of regional glucose hypometabolism often associated with refractory, lesion-related, epilepsy is not well understood. In particular, the role of interictal spiking is controversial since animal models of partial epilepsy have shown that interictal spiking increases glucose metabolism. We addressed this question by studying with positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG) the regional cerebral metabolism in children with focal spiking unrelated to a brain lesion. Patients (11 children with benign childhood epilepsy with centrotemporal spikes (BCECS) and two children without seizures) had on EEG centrotemporal spikes which were either strictly unilateral (ten cases) or strongly predominant on one side (three cases). We looked for an asymmetry in the distribution of cerebral glucose metabolism in our group of patients using statistical parametric mapping (SPM). After spatial normalization, a reversed copy of the 13 scans was obtained, resulting in 26 scans which were assigned to two groups: a group with left-sided centrotemporal spikes and a group with right-sided centrotemporal spikes. Regional glucose metabolism was not statistically different in the two groups. This suggests that metabolic changes associated with interictal spiking cannot be demonstrated by PET with FDG in BCECS, and that this technique could be helpful for the differentiation between idiopathic and symptomatic cases of partial epilepsy in children.
Brain↗
Perisylvian dysgenesis. Clinical, EEG, MRI and glucose metabolism features in 10 patients.
We studied 10 patients who had neurological disorders with a MRI-based diagnosis of perisylvian dysgenesis based on the fact that the parasagittal and centrifugal extremity of the sylvian fissure was abnormally mesial. This abnormality was bilateral in seven cases; in the other three patients, the contralateral sylvian fissure appeared either normal (two cases) or enlarged (open operculum). The perisylvian cortex had a polymicrogyric appearance in most patients. Potential aetiopathogenic factors were determined in four patients. In two of them, ischaemia at mid-gestation was ascribed to death of a co-twin in a context of monozygotic twinning. In the other two patients, who were siblings, genetic factors were suspected. Pseudobulbar palsy was found in eight patients and epilepsy in five patients. We used PET with [18F]fluorodeoxyglucose to test the hypothesis that, despite this clinical and MRI heterogeneity, regional cerebral glucose distribution could have common features in these patients. The analysis of PET data was performed by visual inspection in two cases and by using statistical parametric mapping (SPM) in eight patients compared with a control group. Segmented grey matter MRIs of seven out these patients were also analysed using SPM. We found that the abnormal perisylvian cortex had normal grey matter activity in eight patients and in the other two there was a heterogeneous pattern with areas of preserved metabolism and of decreased metabolism. Metabolic changes were also detected outside the polymicrogyric-like cortex; three patients had hypometabolic areas in cortical regions where the MRI appeared normal and had a normal intensity. When polymicrogyria extended into the white matter, this ectopic dysgenetic cortex was associated with a grey matter pattern within the white matter territory, and was detected by SPM as areas of PET hypermetabolism and MRI hyperintensity. In order to detect possible metabolic changes undetected by the individual analyses, the group of patients was compared with the control group. This comparison revealed bilateral hypometabolism in the frontal opercular cortex. We propose that these PET data be considered in light of the presumed cyto-architectonic pattern of perisylvian dysgenesis, i.e. polymicrogyria. In this malformation, two dense cell layers are separated by a necrotic sparse cell layer. We speculate that the amount of synaptic activity preserved in these dense cell layers depends on the importance and timing of the necrotic process; this hypothesis accounts for the large range of metabolic patterns found, from profoundly decreased glucose metabolism to nearly normal activity.
Adolescent↗
Class, health and justice.
Class inequalities in health are intuitively unjust. Although the link between social class and health status has been fully documented, the precise nature of the injustice has not been made clear. Four alternative views are presented, corresponding to four goals: (1) maximizing the sum total of health; (2) equalizing the health status of higher and lower social classes; (3) maximizing the health status of the lowest social class; and (4) maximizing the health status of the sickest individuals in society. The nature of the injustice is further obscured by several theoretical and empirical questions, like the degree and significance of personal responsibility for illness and the relation of the degree of economic inequality to sum total of health.
Health Care Rationing↗
Cerebello-thalamo-cerebral diaschisis: a case report.
This reports positron emission tomography and [18F]fluorodeoxyglucose (PET-FDG) in a 69-year-old woman who underwent resection of the left cerebellar hemisphere for an acoustic neurinoma 17 years earlier. Functional impairment in cerebral cortical and subcortical structures was evaluated by studying the level of glucose metabolic activity at rest. Relative glucose metabolism was reduced in the prefrontal cortex contralateral to the cerebellar lesion. Contralateral thalamic metabolism was reduced significantly. The results suggest that this phenomenon of "crossed cerebello-thalamo-cerebral diaschisis" is related to a functional depression of the cerebello-thalamo-cortical pathway.
Aged↗
Brain glucose metabolism in anorexia nervosa and affective disorders: influence of weight loss or depressive symptomatology.
Relationships between eating and affective disorders remain complex and unclear. Brain glucose metabolism of anorectic patients has been demonstrated to be reduced both globally and regionally, with a particular relative hypometabolism in the parietal cortex. To explore the possible influence of weight loss or depressive symptomatology on brain metabolism, we studied age- and sex-matched low-weight anorectic and depressed patients, normal-weight depressed patients, and healthy volunteers. Absolute global and regional glucose activity levels were reduced in low-weight patients, with the lowest values being found for anorectic patients. In relative values, anorectic patients showed a significant parietal hypometabolism in comparison to control subjects while they had higher metabolism in the caudate nuclei when compared with the other groups. Absolute hypometabolism of glucose seems to be a consequence of low weight as it was found in both low-weight anorectic and low-weight depressive patients. In addition, absolute glucose values were significantly correlated with body mass index in all subjects. Future positron emission tomographic studies in psychiatric patients should control for alimentary parameters.
Adolescent↗
Stereotactic brain biopsy guided by positron emission tomography (PET) with [F-18]fluorodeoxyglucose and [C-11]methionine.
The aim of the present study was to compare the contribution of the labelled tracers [C-11]methionine (Met) and [F-18]-fluorodeoxyglucose (FDG) in positron emission tomography (PET)-guided stereotactic biopsy of non resectable brain lesions. Twenty-five patients underwent combined Met-PET-, FDG-PET- and computerized tomography (CT)- or magnetic resonance (MR)-guided stereotactic biopsy according to a previously described technique for stereotactic FDG-PET. Met-PET and FDG-PET images were analyzed to determine which tracer offers the best information to guide at least one stereotactic biopsy trajectory. Histological diagnosis was obtained in all patients (23 tumours and 2 non-tumorous lesions). All tumours had an area of abnormal Met uptake and were biopsied under PET-guidance. FDG uptake in the tumour was higher than in the grey matter and was used for target selection in 12 of 23 tumours. Eleven of them were located in the basal ganglia or the brainstem. Met was used for target selection in 11 of 23 tumours where there was no FDG uptake or where FDG uptake was equivalent to that of the grey matter. Ten of them were located in the cortex. Two nontumoral lesions had no Met uptake and were biopsied under CT- or MR-guidance only. Forty-three out of 53 stereotactic trajectories obtained in these 25 patients were based on PET-defined targets and had an area of abnormal Met uptake. These trajectories always yielded a diagnosis of tumour. Moreover, all tumorous trajectories had an area of abnormal Met uptake. Finally, all non-diagnostic trajectories (n = 4) were CT/MR-defined because there was no area of abnormal Met uptake. These results suggest that patients who can benefit the most from Met-PET guidance could be selected pre-operatively. In conclusion, this work shows that Met is a good alternative to FDG for target selection in PET-guided stereotactic brain biopsy.
Adolescent↗
Brain hypometabolism of glucose in low-weight depressed patients and in anorectic patients: a consequence of starvation?
As low-weight anorectic patients presented a global as well as a regional absolute hypometabolism of glucose, we investigated a population of ten age- and sex-matched low-weight depressed patients without anorexia nervosa to evaluate the impact of weight loss on cerebral glucose metabolism evaluated by positron emission tomography and [18F]-fluorodeoxyglucose. Ten age- and sex-matched healthy volunteers were used as controls. Absolute global and regional glucose activity was significantly lower in anorectic and low weight depressed patients than in control subjects. Anorectic patients compared with normal control subjects also showed lower relative metabolism of glucose in the parietal cortex. Within patients, absolute hypometabolism of glucose seems to be a consequence of low-weight while there is a positive correlation between absolute metabolism of glucose and body mass index.
Adult↗
In vivo binding of [18F]altanserin to rat brain 5HT2 receptors: a film and electronic autoradiographic study.
To further validate its use in positron emission tomography (PET), we studied the binding of [18F]altanserin, a specific 5HT2 radioligand, in the rat brain using in vivo autoradiography. Distribution of [18F]altanserin binding was comparable to the in vitro mapping of 5HT2 receptors reported in the literature. Selective displacers were used to test the reversibility and the selectivity of this radioligand. Specific binding of [18F]altanserin in the rat frontal cortex was quantified by direct counting with an electronic imaging system and by quantification on digitalized autoradiograms. Close results of about 30 pmol/g were obtained with both methods. Our data confirmed that [18F]altanserin is a valid tracer for 5HT2 receptors binding studies.
Animals↗
Intracerebral transplantation of fetal ventral mesencephalon for patients with advanced Parkinson's disease. Methodology and 6-month to 1-year follow-up in 3 patients.
In order to launch a new transplantation program for Parkinson's disease (PD), we evaluated the safety and efficacy of fetal ventral mesencephalic grafts in 3 patients with advanced PD. Inclusion criteria and clinical evaluation followed strictly the Core Assessment Program for Intracerebral Transplantation. The transplantation procedure was based on the technique previously described by the groups in Lund (Sweden) and Créteil (France). The putamen contralateral to the site of predominant symptoms was unilaterally grafted in all patients. Magnetic resonance (MR)-based stereotactic guidance with multiplanar correlation was used to define 3 implantation trajectories in the precommissural, commissural, and postcommissural putamen. Fetal ventral mesencephalon was prepared from 6- to 8-week-old human embryos obtained from same-day abortions. Under general anesthesia, 8 deposits of 3 microliters of the fetal tissue were placed 1 mm apart along each implantation trajectory using a customized microsyringe and needle attached to the stereotactic frame. The patients recovered uneventfully from the neurosurgical procedure. Early postoperative MR clearly showed the implantation trajectories reaching the putamen in all patients. The follow-up period was of 12, 9 and 6 months, for each of the 3 patients, respectively. Clinical changes appeared between 3 and 6 months after transplantation and consisted of an increase in the 'on' periods and in quantitative bilateral improvement in the motor timed tests. There was an improvement of the Unified Parkinson's Disease Rating Scale score and an improvement of rigidity. Tremor was unchanged, and there was a slight and transient increase in dyskinesias. Neuropsychological follow-up revealed slight frontal alterations in 2 patients. Positron emission tomography demonstrated an increase of 18F-fluorodopa uptake in the grafted site. Adverse events include a reversible Cushing syndrome secondary to immunosuppression in 1 patient and a transient episode of confusion in another. The results of this study, designed as a prerequisite for a wider transplantation program, are in accordance with those previously reported by others and show that, using standardized neurosurgical techniques and methods of evaluation, transplantation is a reproducible and safe therapeutic approach which provides clinical benefits to patients with advanced PD.
Brain Tissue Transplantation↗
Serotonin 5-HT2 receptor imaging in major depression: focal changes in orbito-insular cortex.
BACKGROUND: Serotonin receptors may play an important role in the pathophysiology of affective disorders. We studied type-2 serotonin (5-HT2) receptors in the brain of patients with major depression. METHOD: Using positron emission tomography (PET) and the selective radioligand [18F]altanserin, we investigated 5-HT2 receptor distribution in eight drug-free unipolar depressed patients and 22 healthy subjects. Data were analysed using Statistical Parametric Mapping 95. RESULTS: In depressed patients, [18F]altanserin uptake was significantly reduced in a region of the right hemisphere including the posterolateral orbitofrontal cortex and the anterior insular cortex. A trend to similar changes was found in the left hemisphere. No correlation was found between the uptake and the Hamilton rating scale score. CONCLUSIONS: Pathophysiology of depression may involve changes in 5-HT2 receptor in brain regions selectively implicated in mood regulation.
Brain Diseases↗