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Biomedical subjects

D Wikler

Publications and source records attributed to D Wikler.

At least 37 records · Page 2Linked to original sources
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

Regional methionine and glucose uptake in high-grade gliomas: a comparative study on PET-guided stereotactic biopsy.

UNLABELLED: Gliomas are regionally heterogeneous tumors. The local relationship between histologic features and radiotracer uptake evaluated by PET should therefore influence analysis and interpretation of PET results on gliomas. This study explored this local relationship as a result of PET guidance of stereotactic biopsies. METHODS: Local histology was confronted to the regional uptake of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 11C-methionine (11C-MET) in 14 patients with high-grade glioma diagnosed during a procedure of PET-guided stereotactic biopsies. We analyzed the uptake of both tracers in regions of interest centered on the stereotactic coordinates of 93 biopsy samples. RESULTS: A semiquantitative analysis revealed a significant regional correlation between 11C-MET and 18F-FDG uptakes. Uptake of both tracers was significantly higher on the site of tumor samples showing anaplastic changes than in the rest of the tumor. Presence of necrosis in anaplastic areas of the tumor significantly reduced the uptake of 11C-MET. CONCLUSION: PET with 11C-MET and 18F-FDG may help to evaluate, in vivo, the metabolic heterogeneity of human gliomas. Anaplasia is a factor of increased uptake of both tracers, but microscopic necrosis in anaplastic areas influences their uptake differently. This finding probably relates to the differences in tracer uptake by non-neoplastic components of necrotic tumors. These results underline the complementary role of 18F-FDG and 11C-MET for the study of brain tumors and favors their use for stereotactic PET guidance of diagnostic or therapeutic procedures.

Adult↗
PubMed1997

Positron emission tomography and brain tumours.

The first applications of positron emission tomography (PET) for the study of brain tumours appeared early in the development of this technology. New trends in these particular PET applications tend to take into account the histological heterogeneity of these tumours and the necessity to integrate PET data in their surgical management. Better knowledge on PET tracers behavior in brain tumours should lead to new clinical uses, in particular in the promising field of cancer treatment evaluation.

Brain Neoplasms↗
PubMed1996

Regional glucose metabolism and histopathology of gliomas. A study based on positron emission tomography-guided stereotactic biopsy.

BACKGROUND: Positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) is widely applied to the study of gliomas. The histology of most gliomas is regionally heterogeneous. The relationship between histologic features and glucose metabolism evaluated by PET with FDG may therefore vary within the limits of the tumor. PET with FDG integrated in the planning of stereotactic brain biopsy allows precise comparison between local FDG uptake and histology. Using this approach, the authors investigated whether glucose metabolism of gliomas is related to anaplasia, and whether PET with FDG detects metabolic heterogeneity that parallels histologic heterogeneity of gliomas. METHODS: A total of 161 biopsy samples collected from 20 PET-guided procedures performed in patients with gliomas (8 low grade astrocytomas, 8 anaplastic astrocytomas, 1 anaplastic oligoastrocytoma, and 3 glioblastomas) were analyzed for the presence or absence of 8 histologic features. Stereotactic coordinates were used to calculate the metabolic rate of glucose (MRGlu) in the region of each biopsy sample. Gray and white matter MRGlu were used to define four metabolic grades that were compared with local histology. RESULTS: The difference in MRGlu expressed as micromoles per 100 g per minute was highly significant between anaplastic and nonanaplastic samples; the median +/- quartile deviation was 23 +/- 16 in anaplastic samples and 18 +/- 5 in nonanaplastic samples (P < 0.005). Even more significant differences were found when MRGlu was normalized to the cortex or to the white matter. Metabolic grades were different in anaplastic and nonanaplastic samples (P < 0.0001). Approximately 75% of samples metabolically graded 3 or 4 demonstrated signs of anaplasia, compared with 10% of samples graded 0 or 1. CONCLUSIONS: FDG uptake in gliomas is anatomically heterogeneous and is regionally related to the presence of anaplasia.

Adult↗
PubMed1996

Coronary vasomotility and myocardial blood flow early after heart transplantation.

Serotonin constricts coronary arteries with endothelial dysfunction, a common abnormality in cardiac transplant recipients. To assess whether endothelial dysfunction is associated with myocardial blood flow (MBF) abnormalities, 24 patients were studied 1 to 12 months after transplantation. Serotonin in increasing doses (1, 10, and 20 micrograms/min for 2.5 min each) was infused into the coronary circulation. Diameters were measured by quantitative angiography. Fourteen patients (group A) had a pronounced artery constriction (diameter reduction > 40%), while in 10 other patients (group B), such a constriction was never reached. No patient had evidence of rejection and all had angiographically normal coronary arteries. MBF was measured at rest and after intravenous dipyridamole with dynamic nitrogen-13 ammonia positron emission tomography (PET). The resting MBF was higher in group A than in group B (94 +/- 12 vs 74 +/- 15 ml/min/100 g of tissue; p < 0.05). During dipyridamole, MBF was not significantly different (191 +/- 53 vs 184 +/- 64 ml/min/100 g; p = NS). Coronary flow reserve (the ratio of perfusion after dipyridamole to perfusion at rest) was significantly lower in group A than in group B (2.08 +/- 0.54 vs 2.66 +/- 0.57; p < 0.05). Thus, coronary hypersensitivity to serotonin in cardiac transplant recipients is associated with elevated resting MBF and reduced coronary flow reserve. Immune mechanisms inducing endothelial injuries and inflammation-related hyperemia may account for these abnormalities.

Coronary Circulation↗
PubMed1996

Sex difference in 5HT2 receptor in the living human brain.

Serotonergic mechanisms are involved in gender-related behaviors and psychiatric conditions like aggression, eating disorders, depression, impulsivity or suicide. We studied gender differences in the living human brain type-2 serotonin receptor (5HT2r). Twenty-two healthy age-matched men and women were investigated using positron emission tomography and the selective radiotracer, 18F-labeled altanserin. Binding was quantified using a non-linear least-squares minimization procedure. We found significantly higher 5HT2r binding capacity in men than in women, especially in the frontal and cingulate cortices. Distinct liability for men and women to suffer from some psychiatric disorders responding to serotonergic agents may be related to differences in brain serotonin receptors.

Adult↗
PubMed1996

Prognostic value positron emission tomography with [18F]fluoro-2-deoxy-D-glucose in the low-grade glioma.

OBJECTIVE: The natural history of the supratentorial low-grade glioma (LGG) of the adult is variable, and its malignant transformation is hardly predictable. Because positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG) has prognostic value in high-grade gliomas, this study was designed to search for a possible relationship between glucose metabolism and risk of malignant evolution in LGGs. METHODS: Positron emission tomography with FDG was performed in 28 patients with LGGs (22 at the time of diagnosis and 6 after the diagnosis). A metabolic grading system based on the visual inspection of the positron emission tomographic images was used. RESULTS: In 19 patients, no area of FDG uptake higher than in the white matter was detected (metabolic Grade 1). All of those patients were alive at the end of the follow-up period. Only one of the patients presented a histological modification 7 months after the diagnosis. Nine patients presented areas of increased FDG uptake (metabolic Grade 2 or 3). Those areas were found in the tumor area in eight patients and in an area of radionecrosis in one. Of the nine patients with FDG "hot spots," six died, two had recurrence but were alive at the end of the follow-up period, and the patient with radionecrosis had no signs of recurrence. CONCLUSIONS: The presence of areas of increased FDG uptake in a histologically proven LGG predicts, in most cases, a deleterious evolution. This metabolic feature, detectable with a noninvasive procedure, may provide a clue to cellular changes, announcing malignant transformation in a tumor that retains the histological features of an LGG. Protocols with aggressive therapeutic strategies in this situation should be considered for evaluation.

Adolescent↗
PubMed1995

Basal ganglia and frontal lobe glucose metabolism. A reproducibility positron emission tomography study.

Positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) is frequently used to study the metabolic correlates of movement and mental disorders. These studies generally focus on changes in the frontal cortex and the basal ganglia. The reproducibility of glucose metabolism estimates in these structures was tested in 13 normal subjects studied at rest using a standard and simple protocol. A reproducible dorsoventral metabolic gradient was demonstrated in the frontal cortex. Such a gradient was not present in the basal ganglia when the upper region of interest in the caudate nucleus, where the lower metabolic rate of glucose was probably attributable to partial volume effects, was not considered. Absolute values of glucose metabolic rates varied by 6.4 to 12.5% in the frontal cortex and by 6.8 to 14.7% in the basal ganglia. Variations in normalized values in the basal ganglia ranged from 4.0 to 8.6%. The number of subjects required to detect statistical differences in group comparison or in test-retest studies was calculated for different anticipated levels of change. With the variability detected in this experiment, less than 10 subjects were expected to be sufficient to detect a 15% change in most regions and in both types of studies.

Adult↗
PubMed1994

Core values in health care reform: a communitarian approach.

Controlling health care costs should allow the nation to provide more health services and higher quality care to more people. The authors are concerned, however, that many of the reform efforts will unwittingly undermine the culture of care in their pursuit of savings and access. This article is a plea to maintain the core moral values and the social and institutional commitments that are essential in the delivery of care, so that the health care community is not turned into a health industry. The authors' communitarian approach aims to preserve the balance between individual rights and social responsibilities, the moral integrity of a caring society, and the unique character of mutual trust between patients and health care personnel. They advocate an orientation toward preventing disease and promoting health, an imperative of reforming the violent, reckless, and costly aspects of American society, and a moral justification for cutting administrative waste, defensive medicine, and excessive profits rather than rationing beneficial and humane health services.

Child↗
PubMed1993

Bioethics and anti-bioethics in light of Nazi medicine: what must we remember?

Only recently have historians explored in depth the role of the medical profession in Nazi Germany. Several recent works reveal that physicians joined the Nazi party in disproportionate numbers and lent both their efforts and their authority to Nazi eugenic and racist programs. While the crimes of the physician Mengele and a few others are well known, recent research points to a much broader involvement by the profession, even in its everyday clinical work. Analogous activities existed in the German legal and industrial communities; disruption of the medical ethic thus sprang from the broader social contexts of Nazi Germany. The new United States Holocaust Memorial Museum, now opening on the Mall in Washington, D.C., will have an opportunity to educate the public about both the great crimes at Auschwitz and other camps, and the gradual but thorough degradation of ethics in the German medical profession. From this presentation, contemporary bioethics can ponder the proper use of the Nazi analogy in bioethical debate.

Attitude of Health Personnel↗
PubMed1991

What has bioethics to offer health policy?

The field of bioethics has quickly become a subject of intense public fascination; and, following on an earlier period of resistance and skepticism, bioethics has been welcomed by clinicians as well. Bioethics, however, is largely a practical activity rather than a scholarly one, and its pretensions as an academic discipline within health policy and health services research must be greeted cautiously. Continuing problems in moral theory suggest that the most secure contributions that bioethics can make to health policy research are analysis and criticism rather than positive moral claims.

Advisory Committees↗