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Biomedical subjects

A Syrota

Publications and source records attributed to A Syrota.

At least 91 records · Page 5Linked to original sources
PubMed1992

Magnetic resonance imaging to monitor pathology of caudate-putamen after excitotoxin-induced neuronal loss in the nonhuman primate brain.

We used MR imaging to locate and monitor in vivo the pathological events taking place 2 to 4 weeks after unilateral striatal injections of ibotenic acid (IA) in the Papio papio baboon. As early as 2 weeks after IA injections, excitotoxic lesions in the caudate and the putamen were directly visualized on T1-weighted images as small areas of low signal intensity. On T2-weighted images, the lesion sites were visualized as areas of high-intensity signal, spreading over larger areas than the corresponding regions in T1-weighted images. These alterations of T2-values in the lesioned striatum persisted 4 weeks after surgery. However, as the striatal degeneration progressed from 2 to 4 weeks after lesion, the size of the areas of high signal intensity on T2-weighted images decreased, whereas the same regions appeared essentially unmodified on T1-weighted images. A marked enlargement of the ipsilateral lateral ventricle (a characteristic of excitotoxic striatal lesions) could be detected 4 weeks after surgery, on both axial T1- and T2-weighted images. Comparisons of MR images with postmortem anatomical data indicated that areas of increased T1 values corresponded to regions of severe neuronal depletion (a direct result of the excitotoxic lesion), whereas areas of increased T2 values corresponded to regions of increased content in astrocytes and ferritin and probably in the early period following lesion (2 weeks) to a superimposed edema.

Animals↗
PubMed1992

Myocardial beta-adrenergic desensitization and neuronal norepinephrine uptake function in idiopathic dilated cardiomyopathy.

Desensitization of myocardial beta-adrenergic receptors may result both from an impairment of the norepinephrine (NE) neuronal uptake function and from an increase in circulating NE concentrations. The respective role of these two mechanisms of desensitization was examined in 18 patients with congestive heart failure related to an idiopathic dilated cardiomyopathy. The neuronal NE uptake system was evaluated by [123I]metaiodobenzylguanidine (MIBG) scintigraphy. The desensitization level of beta-adrenoceptors was assessed as the net increase in peak positive left ventricular (LV) dP/dt during intracoronary dobutamine infusion. Arterial NE concentrations were determined at baseline. To obtain control values, we performed MIBG scintigraphy and determined baseline NE concentration in 12 normal subjects. Cardiac MIBG uptake was significantly decreased in patients as compared with controls. This decrease was related to the severity of the disease based on hemodynamic indexes. The inotropic response to intracoronary dobutamine infusion of heart failure patients correlated with both increased baseline NE concentration and diminished cardiac MIBG uptake (r = -0.63, p less than 0.01 and r = 0.73, p less than 0.001, respectively). These findings indicate that the desensitization process is related both to impaired neuronal NE uptake function and increased circulating NE concentrations. Moreover, a subset of 11 patients with moderate heart failure was identified who had diminished cardiac MIBG uptake but normal circulating NE concentrations. This suggests that impairment of the NE uptake function is an early mechanism of desensitization in idiopathic cardiomyopathy. Cardiac MIBG imaging may be a noninvasive means to assess severity of heart failure patients and may also be used to evaluate therapy effects on myocardial alterations of the adrenergic pathway.

3-Iodobenzylguanidine↗
PubMed1992

The value of pixel per pixel multiharmonic Fourier analysis to assess left ventricular function.

Left ventricular systolic and diastolic function can be assessed by peak ejection and filling rates and their time of occurrence. These parameters can be calculated using two different methods: from the global left ventricular time-activity curve analysed with a four harmonic Fourier fit and from each pixel time-activity curve analysed with two and three harmonics (the values being averaged over the left ventricular region of interest). In both cases, values were normalized for heart rate and end diastolic counts. A study was conducted in a series of 11 patients (six without and five with a previous myocardial infarction but a normal left ventricular function) examined at baseline and during an i.v. dobutamine infusion, at a dose known to increase both peak ejection and filling rates. During dobutamine infusion, analysis of global left ventricular time-activity curve demonstrated a statistically significant increase in both peak ejection and filling rates, but the local analysis showed a more significant increase of these parameters. To assess ventricular function, a local harmonic analysis can be used and appears to be a more sensitive approach than analysis of the global left ventricular time-activity curve. The local analysis provides spatial mapping and a histogram of the parameters which can be used as parametric images to describe systolic and diastolic function.

Dobutamine↗
PubMed1992

Temperature changes induced in human muscle by radio-frequency H-1 decoupling: measurement with an MR imaging diffusion technique. Work in progress.

To investigate temperature increases in tissues during magnetic resonance (MR) imaging or spectroscopy, the authors measured temperature changes in vitro and in vivo (leg of a volunteer) in a condition simulating hydrogen-1 decoupling in MR spectroscopy. Noninvasive measurements were obtained by using the temperature dependence of the translational diffusion coefficient of water. Temperature was measured at 0.5 T (86 MHz) by using a stimulated-echo sequence that included intense gradient pulses and a procedure reducing sensitivity to bulk tissue motion. Calibration curves of the diffusion coefficient against thermocouple-measured temperature were obtained for a gelatin phantom and bovine muscle. Temperature changes were 5.3 degrees C +/- 0.5 at 2.5 cm from the coil in gelatin and 7.7 degrees C +/- 0.5 at 0.7 cm in bovine muscle. The temperature changed by 4.9 degrees C +/- 1.9 at 2.2 cm from the coil in the calf muscle of a volunteer. The H-1 decoupling protocol can be adapted (modifications in transmission power, duty cycle) to reduce heating effects to below safety recommendations.

Animals↗
PubMed1992

Regional cerebral blood flow in childhood autism: a SPECT study.

OBJECTIVE: The authors investigated a possible cortical brain dysfunction associated with infantile autism. METHOD: They measured regional cerebral blood flow with single photon emission computed tomography (SPECT) and xenon-133 in 21 children with primary autism (according to DSM-III-R criteria). Five cortical brain areas including frontal, temporal, and sensory association cortices were examined in order to test the recent hypothesis of cerebral dysfunction in primary autism. Anatomical references for each subject were obtained with computerized tomography or magnetic resonance imaging and were used to delimit the regions of interest for SPECT analysis. RESULTS: When the results from the group with primary autism were compared with an age-matched group of nonautistic children with slight to moderate language disorders (N = 14), no cortical regional abnormalities were found. CONCLUSIONS: It appears that there is no regional cortical dysfunction in primary autism; however, in light of methodological limitations, one cannot exclude the possibility of more localized or subcortical brain dysfunctions in autism.

Autistic Disorder↗
PubMed1992

Changes in regional cerebral blood flow during brain maturation in children and adolescents.

Regional cerebral blood flow (rCBF) was studied by SPECT using 133Xe in 42 children, aged 2 days to 19 years, considered as neurologically normal. rCBF was measured on cortical regions and on the cerebellum and thalamus. Curves for reference values and standard deviation were defined for each region. At birth, cortical rCBFs were lower than those for adults; after birth they increased until 5 or 6 yr of age to values 50%-85% higher than those for adults and thereafter decreased, reaching adult levels between 15 and 19 yr. Neonatal values of rCBF on cerebellum and thalamus were slightly higher than adult level, but not significantly; after age 1, they followed the common pattern for cortical curves. When rCBFs were expressed in percent global CBF, they were lower at birth than adult levels in the cortex, then increased and reached a plateau corresponding to the adult value before the second year of age. The time needed to reach normal adult values differed for each cortical region. The shortest time was found on the primary cortex and the longest on the associative cortex. Cognitive development of the child seems to be related to changes in blood flow of the corresponding brain regions.

Adolescent↗
PubMed1991

The effect of nifedipine on myocardial perfusion and metabolism in systemic sclerosis. A positron emission tomographic study.

We assessed the effect of nifedipine on myocardial perfusion and metabolism in 9 patients with systemic sclerosis, using positron emission tomography with a perfusion tracer (potassium-38) and a metabolic tracer (18F-fluorodeoxyglucose [18FDG]). Nifedipine, 20 mg 3 times daily for 1 week, induced a significant increase in 38K myocardial uptake, a significant decrease in 18FDG myocardial uptake, and a significant increase in the myocardial 38K: 18FDG ratio. These results indicate that the increase in myocardial perfusion is associated with modifications in myocardial energy metabolism, which probably result from a beneficial anti-ischemic effect of nifedipine in patients with systemic sclerosis.

Animals↗
PubMed1991

Complementarity of magnetic resonance spectroscopy, positron emission tomography and single photon emission tomography for the in vivo investigation of human cardiac metabolism and neurotransmission.

The three techniques allowing the noninvasive study of cardiac metabolism, namely magnetic resonance spectroscopy (MRS), positron emission tomography (PET) and single photon emission computed tomography (SPET), all use external detection with stable or radioactive isotopes. These techniques yield different information. PET is quantitative and very sensitive, and therefore only tracer amounts of molecules need to be injected. It allows neurotransmitters and receptors to be studied and a global view of metabolism (oxygen consumption, glucose and fatty acid utilization) to be obtained. SPET also has good sensitivity, but uses gamma-emitting isotopes of heteroatoms. Their longer half-lives allow follow-up for hours or days. MRS is based on stable elements with high (hydrogen 1, phosphorus 31, fluorine 19...) or low (carbon 13, Deuterium) natural abundance. It has very low sensitivity and only millimolar concentrations of substrates can be detected, but various parts of metabolism can be studied. The in vivo measurement of myocardial concentration of substances has many problems that are common to all three techniques (measurement of the volume, measurement of the quantity of each molecule, resolution, partial volume effect, improvement of the signal-to-noise ratio, movement of the organ). The complementarity of the techniques is illustrated by their applications to the study of cardiac metabolism. For instance, the energy metabolism can be studied by 31P-MRS, which detects the high-energy compounds ATP and phosphocreatine, and 13C-MRS yields information on the tricarboxylic acid cycle activity. PET and SPET allow the utilization of fatty acids, the normal fuels of the heart, to be studied. During ischaemia, PET with 18F-fluorodeoxyglucose (18FDG) can determine the glucose consumption and 1H-MRS shows the increase in lactic acid, reflecting anaerobic glycolysis. Comparison of the use of acetate labelled with 11C for PET or 13C for MRS shows the potentials and limitations of each technique. Myocardial perfusion can be evaluated directly with various PET tracers or indirectly with thallium 201 or various technetium-99m-labelled tracers by SPET. No MRS marker of perfusion is so far clinically available. Mainly SPET and PET are used clinically for the investigation of ischaemic heart disease as well as cardiomyopathies, but some initial results using 31P-MRS are being obtained.

Animals↗
PubMed1991

Insulin increases the rate of degradation of 2-deoxy-glucose-6-phosphate in the perfused rat heart: a 31P NMR study.

The effect of insulin on the production and degradation of 2-deoxyglucose-6-phosphate (2DG6P) from 2-deoxyglucose (2DG) in the Langendorff-perfused rat heart was studied by 31P NMR. The 2DG concentrations ranged from 0.25 to 20 mM in the 5 mM acetate perfusion medium, and from 2 to 4 mM in the 12 mM glucose medium. With acetate as the carbon source, the apparent Km for the production of 2DG6P was 7 mM and Vmax was 1.8 mumols/min/mg prot. Insulin enhanced Vmax 7-fold without change in Km of the transporter. With glucose perfusion, insulin had no effect on the initial rate of production of 2DG6P. The interpretation is that glucose phosphorylation is regulated by work when glucose is the energy substrate. In acetate-perfused hearts, in the conditions where the 2DG6P content reached a plateau, the rate of production of 2DG6P (equal to the measured degradation rate, see below) was eight times smaller than the initial rate, both with and without insulin. In glucose-perfused hearts, it was the same as the initial rate. The degradation of 2DG6P upon interruption of 2DG perfusion was exponential. The time constant was the same in acetate or glucose. It was strongly affected by insulin, being 225 +/- 60 min without, and 92 +/- 13 min with insulin. The observation that 2DG6P degradation is sensitive to insulin in the heart shows that its rate may vary. This possibility should be kept in mind in the analysis of PET studies of glucose metabolism.

Acetates↗
PubMed1991

A serial study of regional cerebral blood flow before and after hemispherectomy in a child.

Hemimegalencephaly (HME) is a severe unilateral brain malformation the prognosis of which may be improved by hemispherectomy. HME also provides a unique opportunity to compare normal and pathological hemispheric function in the same patient. We performed a serial functional cerebral imaging study in a child suffering from a neuropathologically confirmed left HME. He was hemispherectomized at 11 months because of intractable epilepsy; this led to cessation of seizures and dramatic psychomotor improvement. Regional cerebral blood flow (rCBF) was studied at 1, 7, 10, 12 and 25 months with single photon computed tomography (SPECT) using 133-Xenon and with simultaneous EEG recording. At one month of age SPECT was performed ictally. During left EEG discharges, rCBF was 40% higher on the left hemisphere than on the right, even in occipital and frontal regions, usually immature at this age. A crossed cerebellar hyperperfusion was also found. At 7 and 10 months, SPECT was performed interictally; rCBF was 45% lower in the left hemisphere than in the right. During follow-up, global and regional CBF values showed normal levels and normal maturation in the right hemisphere except for a mild and transient decrease observed one month after hemispherectomy. SPECT provides an additional procedure for studying hemispheric function in vivo. Serial SPECT imaging may be useful for the preoperative and postoperative evaluation in unilateral cerebral malformation.

Brain↗
PubMed1991

Diagnosis of muscular glycogenosis by in vivo natural abundance 13C NMR spectroscopy.

Natural abundance 13C NMR (nuclear magnetic resonance) spectroscopy was used to distinguish patients suffering from muscle glycogenosis type V (McArdle's disease) from normal subjects by measuring their muscle glycogen content at rest. Proton-decoupled 13C spectra were obtained in 10-15 min from calf muscles at rest. The ratio of the glycogen/creatine signal areas was 12.9 +/- 1.7 in four McArdle's disease patients and 2.0 +/- 0.7 in seven normal subjects. This technique thus allows the non-invasive diagnosis of muscle glycogenosis.

Adult↗
PubMed1991

Kinetic analysis of central [76Br]bromolisuride binding to dopamine D2 receptors studied by PET.

The in vivo kinetic analysis of dopamine D2 receptors was obtained in baboon brain using positron emission tomography (PET) and [76Br]bromolisuride [( 76Br]BLIS) as radioligand. An injection of a trace amount of [76Br]BLIS was followed 3 h later by an injection of a mixture of [76Br]BLIS and BLIS in the same syringe (coinjection experiment). A third injection performed at 6 h was either an excess of unlabeled ligand (displacement experiment) or a second coinjection. This protocol allowed us to evaluate in the striatum of each animal and after a single experiment the quantity of available receptors (B'max) and the kinetic parameters including the association and dissociation rate constants (k + 1VR and k-1, respectively, where VR is the volume of reaction). The cerebellum data were fitted using a model without specific binding. All the parameters were estimated using nonlinear mathematical models of the ligand-receptor interactions including or not including nonspecific binding. The plasma time-concentration curve was used as an input function after correction for the metabolites. An estimate of standard errors was obtained for each PET study and for each identified parameter using the covariance matrix. The average values of B'max and KdVR were 73 +/- 11 pmol/ml tissue and 1.9 +/- 0.9 pmol/ml, respectively. The nonspecific binding was identifiable in the experiment where the last injection corresponded to a second coinjection. We found that approximately 6% of the striatal binding was nonspecific after a tracer injection of [76Br]BLIS. The nonspecific binding appeared to be reversible in the striatum but irreversible in the cerebellum.

Animals↗
PubMed1991

Exercise-induced muscle modifications: study of healthy subjects and patients with metabolic myopathies with MR imaging and P-31 spectroscopy.

Exercise-induced variations in proton signal intensity at magnetic resonance (MR) imaging and in intracellular pH were studied in the forearm muscles of healthy subjects and patients with muscular glycogenoses. The relative increase in T2 was measured from MR images obtained at 0.5 T, and end-exercise pH was measured with surface coil phosphorus-31 spectroscopy at 2 T. Eight healthy subjects showed a relative increase in T2 ranging from 20% to 44% in the flexor digitorum superficialis muscle and a drop in pH ranging from 0.35 to 1.1. Seven patients with muscular glycogenosis (six with McArdle disease and one with phosphofructokinase deficiency) showed only a slight variation in T2 (0%-17%) and no decrease in pH. Variations in T2 and in end-exercise pH were found to be correlated, perhaps reflecting the stimulation of muscular perfusion caused by acidosis.

Adult↗
PubMed1991

The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride.

The striatal D2 receptors of 19 untreated schizophrenics and 14 normal control subjects were investigated with PET and 76Br-bromolisuride. The ratio of radioactivity in the striatum to that in the cerebellum was taken as an index of the striatal D2 receptor density. There was no significant difference between the control and the schizophrenic groups, nor any difference between subgroups of patients defined by clinical type or course of illness, and no relationship between the striatum:cerebellum activity ratio and SANS or SAPS ratings of symptoms. Unlike in the controls, this ratio was not correlated with age in schizophrenics. This study suggests that there is no quantitative abnormality of striatal D2 dopamine receptors in schizophrenia.

Adolescent↗
PubMed1991

PET study of carbon-11-PK 11195 binding to peripheral type benzodiazepine sites in glioblastoma: a case report.

The utility of the peripheral type benzodiazepine site ligand 11C-PK 11195, for imaging human glioma in conjunction with Positron Emission Tomography, relies on a high specific binding of the tracer to tumoral peripheral type benzodiazepines sites. In a patient with glioblastoma, we found that 11C-PK 11195 binding was two-fold higher in the tumor than in normal gray matter and that 30% of tumoral binding could be displaced by a large excess of unlabeled drug. These findings suggest that tumoral retention of the ligand is due, in part, to specific binding.

Aged↗
PubMed1991

Cardiac beta-adrenergic receptor density measured in vivo using PET, CGP 12177, and a new graphical method.

The in vivo quantification of myocardial beta-adrenergic receptor has been obtained in five closed-chest dogs using positron emission tomography (PET). The ligand was racemic (+/-)[11C] CGP 12177, a very potent hydrophilic antagonist of the beta-adrenergic receptor. A kinetic method appeared unsuitable because of the presence of metabolites which made the input function difficult to measure and also inaccurate. Therefore, a graphical method, based on a particular protocol, was proposed. The animals were injected with a trace amount of (+/-)[11C]CGP 12177, which was followed 40 min later by a second injection of radioligand with a low-specific activity. An additional injection of an excess of unlabeled CGP 12177 was administered after 90 min and allowed for the estimation of the dissociation rate constant. The main advantage of this graphical approach is that the results are obtained without having to measure the input function and therefore without estimating the metabolites. The average value of Bmax was 31 +/- 4 pmole/ml of tissue and the dissociation constant was 0.014 +/- 0.002 min-1.

Adrenergic beta-Antagonists↗
PubMed1991

[Abnormalities of the skeletal muscle in hypertrophic cardiomyopathy. Spectroscopy using phosphorus-31 nuclear magnetic resonance].

There have been several reports of electromyographic and histological changes of striated skeletal muscle, especially of the type I oxidative fibres, in hypertrophic cardiomyopathy. In order to determine whether these anomalies also cause metabolic changes, a P-31 magnetic resonance spectroscopic study was undertaken at rest and on exercise in 5 pauci-symptomatic patients and 10 control subjects. The 5 patients had primary hypertrophic cardiomyopathy without alteration of systolic function or signs of congestive cardiac failure (Stages I or II). There were no clinical signs of myopathy. None of the patients were receiving betablocker therapy at the time of investigation. No significant difference was observed at rest. Intracellular acidosis was particularly pronounced in 2 of the 5 patients at the peak of exercise. In addition, the phosphocreatine recovery time (T1/2) was longer in the patient group (3.4 +/- 1.7 vs 1.6 +/- 0.9 mn; p less than 0.01) suggesting a mitochondrial metabolic oxidation abnormality. These results suggest that some patients with primary hypertrophic cardiomyopathy have abnormalities of mitochondrial oxidation in their striated skeletal muscle which can be demonstrated by P-31 magnetic resonance spectroscopy. This would suggest a global abnormality of striated muscle which, at a more advanced stage of the disease, could account for decreased effort tolerance in these patients.

Adult↗