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Biomedical subjects

D Comar

Publications and source records attributed to D Comar.

At least 55 records · Page 3Linked to original sources
PubMed1984

llC labelling of a protein: concanavalin A.

A method is described for the 11C labelling of a phytoagglutinin, concanavalin A, involving reductive methylation by formaldehyde and sodium cyanoborohydride. The reaction mixture is then chromatographed by gel permeation. The quantities (20-80 mCi) and specific activities (20-170 mCi/mg) obtained are such that a practical application of the method is possible. No evidence was found, however, of any preferential uptake of concanavalin A by Krebs II ascite cells in Swiss mice.

Animals↗
PubMed1984

Synthesis of ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo [1,5-a] [1,4]benzodiazepine-3-carboxylate (RO 15.1788-11C): a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography.

A method of labelling ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine-3-carboxylate (RO 15.1788 11C), a benzodiazepine antagonist with carbon-11 has been developed. RO 15.1788-11C was prepared by methylation of the nor derivative by I11CH3. About 100 mCi (maximum 153 mCi, 5.66 GBq) of the chemically and radiochemically pure labelled product were obtained within 25 min with a specific activity on average of 1100 mCi/mumol (maximum 1740 mCi/mu mol--64.4 GBq/mu mol). Preliminary results obtained after i.v. administration in the baboon have shown RO 15.1788-11C to be of interest as a benzodiazepine radioligand for the in vivo study of benzodiazepine receptors by positron emission tomography.

Animals↗
PubMed1984

Local interrelationships of cerebral oxygen consumption and glucose utilization in normal subjects and in ischemic stroke patients: a positron tomography study.

With the use of positron emission tomography (PET) and the 15O steady-state-[18F]fluorodeoxyglucose combined method, the local interrelationships between the cerebral metabolic rate for oxygen (CMRO2) and the cerebral metabolic rate for glucose ( CMRGlc ) were investigated in control subjects and in stroke patients. In addition to the classic in vivo autoradiographic approach, a kinetic method was used to measure CMRGlc because it was expected to be more reliable in cerebral ischemia. In control subjects local coupling between CBF, CMRO2, and CMRGlc was confirmed, and acceptable values for the CMRO2/ CMRGlc ratio were found; the latter, however, was lower in white matter than in gray. Uncoupling between CMRO2 and CMRGlc was observed in all stroke patients, suggesting that (1) enhanced anaerobic glycolysis occurred both in reperfused recent infarcts and in chronically ischemic tissue, and (2) substrates other than blood-borne glucose were being oxidized at the borders of recent infarcts. However, methodological uncertainties presently make such observations only tentative. Finally, a coupled depression of CMRO2 and CMRGlc was found in the contralateral cerebellum.

Aged↗
PubMed1984

Local cerebral glucose utilisation in treated and untreated patients with Parkinson's disease.

Using the 18f-fluoro-2-deoxy-d-glucose technique and positron emission tomography (PET), the local cerebral glucose utilisation (1CMRGlc) was measured in four non-demented patients with early-onset, bilateral Parkinson's disease characterised by the predominance of akinesia. The study was done twice, first in the untreated condition, and then after levodopa had been resumed. Despite a marked clinical improvement, we found no alteration in 1CMRGlc between the first and second studies in any of the brain structure analysed. Compared to control values, 1CMRGlc in the basal ganglia was moderately increased in both studies. These essentially negative findings agree with most previous human or animal studies, and indicate that the functional alterations in the central dopaminergic systems of patients with Parkinson's disease have metabolic correlates that are too small to be demonstrated by current PET devices.

Antiparkinson Agents↗
PubMed1983

[Positron emission tomography in the physiopathological study of cerebral ischemia in man].

The development of positron emission tomography now allows the local study of cerebral blood flow, oxygen consumption and glucose utilization in ischemic stroke patients. In recent cerebral infarction, a disruption of the normal couple between flow and metabolism is almost constantly observed: in the first few days cerebral blood flow is either inadequate (persistent ischemia) or over-abundant ("luxury perfusion"), whereas a late "luxury perfusion" is almost constant within the necrotic area between the 10th and the 40th day. Threshold values for cerebral blood flow and oxygen consumption that are ultimately associated with necrosis or tissue integrity have been determined. A metabolic depression without C.T. Scan counterpart has been observed in various brain structures remote from the infarcted area per se. Lastly, the hemodynamic and metabolic effects the superficial-temporal-middle-cerebral-artery anastomosis have been studied.

Brain Ischemia↗
PubMed1983

[55Co]- and [64Cu]DTPA: new radiopharmaceuticals for quantitative tomocisternography.

The diethylenetriaminepentaacetic acid (DTPA) complexes of the convenient half-life positron emitters 55Co and 64Cu have been prepared for quantitation of cerebrospinal fluid (CSF) kinetics in different areas of the brain using positron emission tomography. The radionuclides are prepared by proton bombardment of natural nickel (58Ni(p, alpha)55 Co and 64Ni (p,n)64Cu reactions). The chemical separation of the radionuclides from the target is described, and the production yields, radionuclidic purities and specific activities are given.

Brain Diseases↗
PubMed1983

[Water diffusion and measurement of cerebral blood flow by C15O2 inhalation].

Measurement of local Cerebral Blood Flow (CBF) using the C15O2 continuous inhalation technique coupled with Position Emission Tomography (PET) rests on the assumption that the in vivo labelled water (H215O) of blood diffuses freely within the brain water pool. This requirement however, may be disputed: in the rhesus monkey, Eichling et al (1974) showed a linear relationship between the single-pass extraction of water (E) and CBF after intra-carotid H215O injection, such that E decreases as CBF increases. Such a limitation in water transport across the blood brain barrier has also been suggested to exist in man (Paulson, 1977). In order to verify its possible effects on measured CBF in baboons, simple computer analysis was performed comparing the data obtained with CBF values reported in similar experiments, but using a freely diffusible inert gas (133Xe). This allowed calculation of a water extraction index (IE), which was shown to decline as CBF increased. This result may be considered as a presumption of the part played by the limited water diffusibility on the final CBF values, but other factors must also be considered, such as the inescapable admixture of grey and white matter (partial volume effect), a limitation of present day PET technology.

Animals↗
PubMed1983

Brain regional pharmacokinetics of 11C-labeled diphenylhydantoin: positron emission tomography in humans.

We used positron emission tomography to study the regional cerebral pharmacokinetics of 11C-labeled diphenylhydantoin (11C-DPH), which was given intravenously to 10 patients (8 intractable partial epileptics and 2 nonepileptics). In the nonaffected hemisphere, 11C-DPH concentration in gray matter reached equilibrium with blood within 20 minutes but was still rising at 60 minutes in white matter, where equilibrium was too slow to be detected owing to the fast physical decay of 11C. Brain-blood concentration ratios at 50 minutes were 1.37 and 1.06 in gray and white matter, respectively, similar but less variable than steady-state DPH ratios reported in human brain surgical samples. There was no indication that normal brain regions of medically resistant epileptics bind DPH less effectively than in nonepileptic patients. Brain and blood 11C-DPH concentrations were well correlated, confirming that the latter gives a reliable estimate of the former in unaffected brain regions.

Adolescent↗
PubMed1983

[11C-Ro15-1788 and 11C-flunitrazepam, two coordinates for the study by positron emission tomography of benzodiazepine binding sites].

In vivo binding of a benzodiazepine (flunitrazepam-C11) and a benzodiazepine antagonist (Ro 15-1788-C11) were studied with positron emission tomography. Advantages and disadvantages of each drug for studying specific in vivo binding sites are presented. The results obtained indicate that Ro 15-1788-C11 is a better in vivo radiocoordinat than flunitrazepam-C11.

Animals↗
PubMed1983

[In vivo study of benzodiazepine receptors using positron emission tomography].

The results obtained by positron-emission tomography in an "in vivo" study on the baboon using a benzodiazepine (flunitrazepam) labeled with carbon-11 are presented. The specificity of "in vivo" binding of Flunitrazepam-11C was demonstrated by competition with Lorazepam in the brain, but it was not possible to verify the criterium of stereospecificity "in vivo". The preliminary results of a study carried out under the same conditions on RO 15 1788 11C show the interest of using this labeled antagonist as an "in vivo" ligand for the specific binding sites of benzodiazepines in positron-emission tomography.

Animals↗
PubMed1982

Positron emission tomography in a case of experimental focal epilepsy in the baboon.

Repetitive limbic status epilepticus was produced in one baboon by intraamygdaloid microinjection of kainic acid. Brain metabolism was analysed by positron emission tomography (PET) after intravenous administration 18fluorodeoxyglucose (18FDG). In a control examination the distribution of 18FDG was symmetric in homologous parts of the brain. In contrast, during the epileptic state a restricted zone, the fronto-temporal region, showed increased 18FDG incorporation. This region corresponded to the side of kainic acid injection and to the limbic epileptogenic focus as demonstrated by EEG recording. The use of the non-invasive PET technique is suggested as an adjunct to classical EEG and clinical observation for the localization of an epileptic focus generating a status epilepticus.

Animals↗
PubMed1982

Synthesis and in vivo characteristics of [2-11 C]5,5-dimethyloxazolidine-2,4-dione (DMO).

No-carrier-added [2-11 C]5,5-dimethyloxazolidine-2,4-dione (DMO) has been prepared rapidly and in good radiochemical yield. The synthesis involves in situ conversion of phosgene to diethyl carbonate which reacts with 2-hydroxy-2-methylpropionamide to yield labeled DMO. HPLC purification provided up to 1.85 GBq (50 mCi) of pure [11C]-DMO for injection. The product's in vivo distribution was examined in mice and rabbits. The results are encouraging for further application to in vivo measurement of intracellular pH using positron tomography.

Animals↗
PubMed1982

[A 15oxygen positron study of relative local perfusion and oxygen extraction of the brain in lacunar hemiparesis (author's transl)].

The oxygen-15 non-invasive continuous inhalation technique coupled with positron emission tomography (PET) allows the local study of cerebral blood flow and oxygen metabolism. Recent PET studied have demonstrated the frequent occurrence of widespread metabolic depression remote from the site of middle cerebral artery territory infarct per se, especially over the cortical mantle and thalamus ipsilaterally, and over the cerebellar hemisphere contralaterally. These phenomena have been taken as indicative of a transneural depression (i.e. diaschisis). We thought interesting to study the possible occurrence of such abnormalities in patients with lacunar syndromes. We have applied the 15O technique to seven patients (2 with pure motor hemiplegia, 5 with ataxic hemiparesis) in whom no large causal ischemic lesion could be demonstrated on CT Scans; in only one patient was a lacunar lesion, presumably responsible for the clinical deficit, evidenced. Compared to a set of 19 patients without brain disease, the semi-quantitative results (analyzed in terms of asymmetry indices between homologous brain regions) in our patients did not disclose any pathophysiologically significant abnormality. More specifically, no evidence of physiological dysfunction similar to that reported in internal carotid artery territory infarcts, was detected over the cerebral or the cerebellar cortices. These original findings are commented upon in view of the presumably small size and the uncertain topography of the causal lesion.

Aged↗
PubMed1981

The kinetics and displacement of [11C]flunitrazepam in the brain of the living baboon.

The distribution and kinetics of [11C]flunitrazepam in the brain were studied by positron emission tomography in the living baboon. Flunitrazepam was labelled on the methyl group with the 20 min positron emitter carbon 11. Fifteen to 25 mCi corresponding to 15-30 nmol were injected i.v. and sequential tomographic pictures of the brain were obtained. In some experiments, therapeutic doses of various benzodiazepines were injected i.v. subsequently in order to study the displacement of the radioactive ligand from brain structures. Lorazepam was shown to displace [11C]flunitrazepam from brain tissue, although other benzodiazepines (chlordiazepoxide, Ro 116896 and Ro 116893) led to a redistribution of the radioactive ligand in the body accompanied by an increase of brain radioactivity.

Animals↗