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Biomedical subjects

B Sadzot

Publications and source records attributed to B Sadzot.

At least 73 records · Page 4Linked to original sources
PubMed1990

Quantitative analysis of 18/FDG-PET in the presurgical evaluation of patients suffering from refractory partial epilepsy. Comparison with CT, MRI, and combined subdural and depth. EEG.

CT, MRI, 18/FDG-PET and Depth. EEG, performed with subdural and depth electrodes were part of the presurgical evaluation in 22 patients. Statistical analysis of 18/FDG-PET was performed to compare cerebral utilization of glucose to that of normal age matched controls. The findings of CT, MRI, and quantitative analysis of PET are compared with those of ictal Depth. EEG. A positive correlation between CT and Depth. EEG was obtained in 23% of the patients and between MRI and Depth. EEG. in 50%. For both imaging techniques a negative correlation was found in 5%. Regional abnormalities were found with quantified PET in 95% of the patients and were concordant with Depth. EEG. for side of onset in 77% of the patients and for lobe of onset in 59%. A possibly false localising PET result for lobe of onset was obtained in 8 patients (36%). Limitations of PET were most apparent in patients with regional mesiolimbic or bilateral seizure onset. A favourable outcome of surgery was associated usually with positive convergence of both methods. PET may be a valuable contribution to the research and management of partial complex epilepsy, but at present cannot be considered a reliable alternative to invasive EEG methods in patients without clear unilateral focus localization on surface EEG.

Adolescent↗
PubMed1990

Detection and quantification of opiate receptors in man by positron emission tomography. Potential applications to the study of pain.

Opiate receptors in the brain are the target of endogenous opioids and of exogenous synthetic opiates. It is well established that these receptors play a major role in the modulation of pain perception. With positron emission tomography (PET) and the appropriate radioligands, it is now possible to image and quantify neuroreceptors in vivo. We used 11C-diprenorphine and the extremely potent mu opiate receptor agonist 11C-carfentanil to image the distribution of opiate receptors in the human brain and to quantify their density, affinity, and occupancy. Several important methodological aspects of the in vivo opiate receptor labeling with PET in relation to the study of pain are considered in this paper. Monitoring receptor occupancy by opiate drugs as a function of pain relief has the potential to reveal better ways to treat pain.

Humans↗
PubMed1990

Comparison of [11C]diprenorphine and [11C]carfentanil binding to opiate receptors in humans by positron emission tomography.

The kinetics and regional distribution of [11C]carfentanil, a mu-selective opiate receptor agonist, and [11C]diprenorphine, a nonselective opiate receptor antagonist, were compared using paired positron emission tomography studies in two normal volunteers. Kinetics of total radioactivity (counts/mCi/pixel) was greater for [11C]diprenorphine than [11C]carfentanil in all regions. [11C]Carfentanil binding (expressed as the total/nonspecific ratio) reached near equilibrium at approximately 40 min, whereas [11C]diprenorphine showed a linear increase until approximately 60 min. Kinetics of specific binding demonstrated significant dissociation of [11C]carfentanil from opiate receptors, whereas little dissociation of [11C]diprenorphine was observed during the 90-min scan session. Regional distributions of [11C]carfentanil and [11C]diprenorphine were qualitatively and quantitatively different: Relative to the thalamus (a region with known predominance of mu-receptors), [11C]diprenorphine displayed greater binding in the striatum and cingulate and frontal cortex compared to [11C]carfentanil, consistent with labeling of additional, non-mu sites by [11C]diprenorphine. We conclude from these studies that [11C]diprenorphine labels other opiate receptor subtypes in addition to the mu sites selectively labeled by [11C]carfentanil. The nonselective nature of diprenorphine potentially limits its usefulness in defining abnormalities of specific opiate receptor subtypes in various diseases. Development of selective tracers for the delta- and kappa-opiate receptor sites, or alternatively use of unlabeled inhibitors to differentially displace mu, delta, and kappa subtypes, will help offset these limitations.

Adult↗
PubMed1989

In vivo labeling of central benzodiazepine receptors with the partial inverse agonist [3H]Ro 15-4513.

Ro 15-4513 is an imidazobenzodiazepine and a partial inverse agonist at the central benzodiazepine receptors (BZDr). It has been shown to antagonize behavioral and biochemical effects of ethanol. In vivo binding of [3H]Ro 15-4513 was evaluated in mouse brain. After intravenous injection [3H]Ro 15-4513 was readily taken up by the brain and distributed to brain areas enriched in benzodiazepine receptors. Binding was specific for central BZDr, saturable and reversible. A high degree of specific binding, relative to non-specific binding, was achieved. Analysis of dissociation kinetics revealed that [3H]Ro 15-4513 was retained significantly longer in hippocampus compared to other brain regions. In view of the known distribution of benzodiazepine receptor subtypes, this suggests that, in vivo, [3H]Ro 15-4513 has a higher affinity for benzodiazepine receptors type II and may explain quantitative differences in the regional distribution of this ligand compared to the antagonist [3H]Ro 15-1788. We conclude from these studies that Ro 15-4513 is a suitable ligand for in vivo studies of benzodiazepine receptors. Labeled with a positron-emitting isotope, it could be used with positron emission tomography to study BZDr in man under a variety of conditions.

Animals↗
PubMed1989

Hallucinogenic drug interactions at human brain 5-HT2 receptors: implications for treating LSD-induced hallucinogenesis.

It has been shown that the hallucinogenic potencies of LSD, the phenylisopropylamines, such as DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) and DOI (4-iodo-2,5-dimethoxyphenylisopropylamine), and the indolealkylamines, such as DMT (dimethyltryptamine) and 5-OMe-DMT (5-methoxy-dimethyltryptamine), strongly correlate with their in vitro 5-HT2 receptor binding affinities in rat cortical homogenates. In order to ascertain if this correlation applies to human 5-HT2 receptors as well, we examined the affinities of 13 psychoactive compounds at 3H-ketanserin-labelled 5-HT2 receptors in human cortical samples. Both radioligand binding and autoradiographical procedures were used. As in rat brain, d-LSD was the most potent displacer of 3H-ketanserin specific binding with a Ki of 0.9 nM. The phenylisopropylamine DOI also displayed high affinity (Ki of 6 nM). Stereospecific interactions were found with DOB; (-) DOB had a Ki of 17 nM while (+) DOB had a Ki of 55 nM. The behaviorally active compound DOM (4-methyl-2,5-phenylisopropylamine) had an affinity of 162 nM while its behaviorally less active congener iso-DOM had an affinity of 6299 nM. The indolealkylamines 5-OMe-DMT and DMT competed with moderate affinities (207 and 462 nM, respectively). In general, Hill coefficients were significantly less than unity which is consistent with an agonist interaction with 5-HT2 receptors. MDMA, a substituted amphetamine analog was inactive with a Ki of greater than 10 microM. A strong correlation was found for the hallucinogen affinities and human hallucinogenic potencies (r = 0.97). Also, human and rat brain 5-HT2 receptor affinities were strongly correlated (r = 0.99). These results strongly support the hypothesis that the hallucinogenic effects of these drugs in humans are mediated in whole or in part via 5-HT2 receptors. Furthermore, these studies imply that treatment with 5-HT2 receptor antagonists may be effective in reversing the hallucinogenic effects caused by the ingestion of LSD and LSD-like drugs.

Animals↗
PubMed1987

[Study of regional cerebral glucose metabolism, in man, while awake or asleep, by positron emission tomography].

Measurements of regional cerebral glucose uptake by the 18F-fluorodeoxyglucose technique (18FDG) and positron emission tomography (PET) along with polygraph recordings were made serially during relaxed wakefulness and different stages of nocturnal sleep in two right-handed normal volunteers. During stage III-IV sleep, values declined diffusely in both hemispheric regions (-31%), thalamus (-33%), cerebellum (-33%) and brain stem (-25%). During paradoxical sleep regional values increased diffusely compared with slow wave sleep. Compared to wakefulness, regional metabolic values seemed to increase but the results were more variable from one volunteer to the other. These preliminary data indicate important regional alterations in cerebral metabolism between sleep states.

Adult↗
PubMed1987

[Paraneoplastic limbic encephalopathy, inappropriate ADH secretion and recurrent subclinical epileptic seizures. Clinical, anatomo-pathological and metabolic correlations by positron emission tomography].

We report a case of limbic encephalopathy clinically characterized by a progressive amnestic syndrome and many EEG seizures mainly localized on the left temporal area. Biological investigations revealed diabetes mellitus and a syndrome of inappropriate antidiuretic hormone secretion (IADH). Haemodynamic and metabolic studies by positron-emission tomography showed an important increase in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen on the left anterior temporal region precisely where the electrical seizures were recorded. Nine months later, severe disorders of memory and a dramatic decrease in CBF and CMRO2 on the same area region were present. At autopsy, a small size oat cell bronchial carcinoma was found with metastases in two small adjacent lymph nodes. Neuropathological examination showed atrophy (neuronal loss, protoplasmic gliosis) in the amygdala; where there was in addition an area of nodular gliosis. The hippocampus and parahippocampal gyrus lesions were severe on the left and moderate on the right side. The authors discuss the nosology of their case in the paraneoplastic syndromes and, with a review of the literature, the role of ADH and cellular hyperactivity in the pathogenesis of specifically localized neuronal alterations.

Amnesia↗
PubMed1986

[Study of cerebral metabolism and blood flow in partial complex epilepsy and status epilepticus in man using positron emission tomography].

Positron Emission Tomography (PET) with the oxygen-15 steady state inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen consumption (CMRO2) and oxygen extraction ratio (OER) in 25 patients with partial complex seizures during the interictal state, in 1 patient with recurrent temporal seizures and in 3 patients whose EEGs were characterized by periodic lateralized epileptiform discharges (PLEDs). Interictal scans showed temporal zone(s) of hypoperfusion and hypometabolism in 80% of patients with normal X-ray CT Scan. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the EEG abnormalities. Comparison of the different values of CBF, CMRO2 and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease in OER, the latter was always the most prominent in the region of the focus determined by serial EEG recordings. The observed imbalance between blood flow and oxidative glucose metabolism could suggest an impairment of O2 utilization by the mitochondria in the epilepticus focus during seizures or status epilepticus.

Brain↗
PubMed1986

Regional cerebral blood flow and metabolic rates in human focal epilepsy and status epilepticus.

Positron emission tomography with the oxygen-15 steady state or bolus inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen extraction ratio (OER) and oxygen consumption (CMRO2) in 25 patients with partial complex seizures during the interictal state and in 5 patients during status epilepticus. Glucose utilization (CMRglu) was also studied in one case of status epilepticus with the 18F-fluorodeoxyglucose technique (18FDG). Interictal scans showed zone(s) of hypoperfusion and hypometabolism without significant variation of the OER in approximately 80% of patients. In 62%, there was a strong correlation between the overall EEG localization and the area(s) of hypoperfusion and hypometabolism. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the electroencephalograph (EEG) abnormalities. Comparison of the different values of CBF, CMRO2, and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease of OER; the latter was always the most prominent in the region of the epilepticus focus determined by serial EEG recordings. These results showed that the supply of oxygen by blood flow is large enough to meet metabolic demand. When comparing these values with CMRglu, it appeared that the relative changes in CMRglu and CBF were very similar, indicating that the increase in blood flow correlated with the enhancement in glucose utilization. The observed imbalance between blood flow, glucose utilization, and oxygen consumption could suggest that an impairment of oxygen utilization by the mitochondria could occur in the epileptic focus during prolonged status epilepticus.

Cerebrovascular Circulation↗
PubMed1986

[Hemodynamic and metabolic study using positron emission tomography in a case of right thalamo-capsular ischemic stroke].

The authors report the results of a Positron Emission Tomographic (PET) study of local cerebral blood flow and oxygen consumption in one patient with a right capsulo-thalamic ischemic lesion. That lesion is well demonstrated using X-ray CT Scan. PET study demonstrates a decreased perfusion and metabolism at three levels: first in right thalamus region, second in whole right hemisphere, more marked at orbitofrontal area and third at the level of the left cerebellar hemisphere. The authors point out the usefulness of PET studies which allow a better understanding of clinical signs by demonstrating functional consequences of damage in deeply located structures such as thalamus and internal capsule on cerebral and cerebellar cortices.

Brain↗
PubMedDate not supplied

Non-invasive methods to study drug disposition: positron emission tomography. Detection and quantification of brain receptors in man.

Positron emission tomography (PET) has been used mostly for the study of brain blood flow and metabolism in normal controls and in a variety of neurological and psychiatric conditions. With the appropriate radiotracers, PET also allows non-invasive imaging and quantification of a growing list of neuroreceptors, the target of most psychotropic drugs. For example, 11C-carfentanil and 11C-diprenorphine, two potent opiate ligands, have been used to label opiate receptors in vivo in man. Methods have been developed to quantify receptor studies with PET in terms of receptor density and affinity. PET is a unique tool that now allows measurement of receptor occupancy in vivo and could be used by the pharmacologist to optimize drug treatment.

Brain↗
PubMedDate not supplied

Anatomical localization for PET using MR imaging.

Accurate localization of an imaging plane of interest is often needed prior to a positron emission tomographic (PET) study. We have developed a simple method for accurate and reproducible selection of an imaging plane for PET using magnetic resonance (MR) imaging. This method is useful when optimal sampling of specific brain structures, such as small subcortical nuclei, or when a specific imaging angle is required for the PET study. An external localizing device, consisting of a series of tubes visible on MR, is affixed to an individually fitted thermoplastic mask. This mask system is worn by the patient during both the MR and PET studies. A plane of interest is planned from the sagittal MR image and defined by its relation to the localizing device and to the MR scanner's "landmark" or reference position. This plane is transferred to the mask by means of a calibrated alignment laser. The coplanar acquisition of MR and PET images allows individualized analysis of brain structure-function relationships. Phantom studies demonstrated the accuracy and reproducibility of imaging plane selection by this method to be within 1 mm and 1 degree. Application of the localization protocol in a human subject is also presented.

Adult↗
PubMedDate not supplied

[Reversible posterior leukoencephalopathy syndrome].

Reversible posterior leukoencephalopathy refers to a clinicoradiological syndrome observed in patients presenting with acute or subacute symptoms of various intensity including seizures, headache, vomiting, confusion and visual abnormalities. The radiological features are reversible bilateral white matter abnormalities predominantly located in the posterior regions of the cerebral hemispheres, demonstrated by computed tomography or, better, by magnetic resonance imaging. This syndrome mostly occurs in patients with hypertensive encephalopathy or in immunosuppressed patients. The recognition of this syndrome is critical as delay in the diagnosis or treatment can result in permanent neurological deficit while early prompt control of blood pressure or withdrawal of causative drugs can reverse the syndrome.

Adult↗
PubMedDate not supplied

[Clinical case of the month. Rendu-Osler-Weber disease: a rare case of stroke in the young].

Rendu-Osler disease or hereditary hemorragic telangiectasia is a group of autosomal dominant diseases characterized by angiodysplasic lesions in the skin, mucous membranes and viscera with risks of recurrent bleedings. Neurological complications have been described in 10-30% of these patients, most often hemorrhagic or septic. More exceptionally, ischemic strokes occur in these patients, particularly if they have pulmonary arteriovenous malformations. We report the observation of a 25 year old man who developed a latero-protuberantial stroke. The explorations revealed pulmonary AV malformations and nasal telangiectasias that led to the diagnostic of Rendu-Osler disease. This affection should be considered as a potential cause of cerebral ischemic attack, particularly in young patients without risk factors.

Adult↗