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Biomedical subjects

S Pascal

Publications and source records attributed to S Pascal.

At least 19 recordsLinked to original sources

Viability of neocortical function shown in behavioral activation state PET studies in Alzheimer disease.

Twenty subjects with mildly to moderately severe Alzheimer disease (AD) and 14 normal elderly control subjects were studied using [18F]fluorodeoxyglucose and positron emission tomography (PET) to investigate regional cerebral glucose metabolism during both a resting state and a behavioral activation state, utilizing a reading memory task (RMT). The RMT produced significant global metabolic activation of 15 +/- 15% in normal subjects and 11 +/- 13% in AD subjects. The occipital regions were preferentially activated, but all regions in both groups were also significantly activated. The RMT did not allow a better discrimination of AD patients from normal controls on the basis of regional metabolic deficits. Regions in the AD group that were individually classified as hypometabolic during rest also exhibited metabolic activation. The apparent viability of hypometabolic regions in AD patients challenges current hypotheses regarding the cause of abnormal metabolism in AD.

Alzheimer Disease

Scintigraphy with J001 macrophage targeting glycolipopeptide. A new approach for sarcoidosis imaging.

Scintigraphy with radiolabeled J001 as a ligand for macrophage targeting is a new approach for sarcoidosis imaging. J001 is a fully characterized acylated peptido-poly (1,3) galactoside isolated from Klebsiella membrane proteoglycans and able to bind electively recruited macrophages. Its physiochemical properties allow rapid absorption by the respiratory tract when this agent, labeled by 99m technetium, is administered as an aerosol. Images are obtained within 3 to 5 h after inhalation. In the present study, we determined the ability of J001 scintigraphy to localize areas of sarcoidosis involvement in 22 patients compared with gallium scanning in ten of them. Nineteen patients underwent bronchoalveolar lavage (BAL) and serum angiotensin-converting enzyme (ACE) assay. J001 scintigraphy was also performed on a control group of six patients with extrathoracic melanoma, in whom J001 scintigraphy was used to evaluate the cutaneous extent of the tumor and the lymph node involvement. In this control group, no fixation appeared in the thoracic area. In the sarcoidosis group, 18 positive results were observed. One stage 0 patient had a mediastinal fixation. Five of the six stage 1 patients had a fixation located in the mediastinum, the lungs, and the wrists. Five of the six stage 2 patients had positive foci located in the mediastinum or the lung areas and in the myocardium in one of them. Six of the nine stage 3 patients had positive J001 scintigraphy occurring in the lungs and/or the mediastinum. One patient had a fixation on the main bronchi. J001 scintigraphy and gallium scanning, performed in ten patients, were positive in seven of them. There were discrepancies between the BAL results and J001 scintigraphy, as well as between the ACE results and J001 scintigraphy. In conclusion, 99mTc-J001 scintigraphy appears to be a sensitive and rapid technique for the imaging of thoracic sarcoidosis at the three stages of the disease.

Adult

[Antibiotics in aerosols].

The treatment of bronchopulmonary infections using antibiotics administered by aerosol should enable a better local concentration of the drug to be achieved whilst reducing the side effects. The parameters of the aerosol kinetics in the airways lead to an interaction of the physico-chemical characteristics of the molecule, the material used for the aerosolisation and also the conditions on inhalation. Intrabronchial concentrations are lower than after endotracheal instillation but remain 10 to 40 times greater than after parenteral administration. Antibiotic aerosols are relatively well tolerated but should be used with care and caution in patients susceptible to bronchial hyperreactivity. Aerosol treatment is currently little used outside those patients with mucoviscidosis and dilatation of the bronchi. In mucoviscidosis aerosol antibiotics are used in the acute situation to achieve cures of infection and in the chronic situation to prevent colonisation by Pseudomonas. Antibiotic aerosols are efficacious in the treatment of acute infectious episodes but do not seem to carry any additional clinical benefit which is superior to antibiotics administered parenterally. It could nonetheless constitute a useful alternative in simplifying treatment in the home. This style of treatment remains to be further explored in a more complete fashion in bronchial dilatation.

Aerosols

Evaluation of a neural-network classifier for PET scans of normal and Alzheimer's disease subjects.

The value of PET as an objective diagnostic tool for dementia may depend on the degree to which abnormal metabolic patterns can be detected by quantitative classification methods. In these studies, a neural-network classifier based on coarse region of interest analyses was used to classify normal and abnormal FDG-PET scans. The performance of neural networks and of an expert reader were evaluated by cross-validation testing. When the "abnormal" class was represented by subjects with clinical diagnoses of "Probable Alzheimer's," the areas under the relative-operating-characteristic (ROC) curves were 0.85 and 0.89 for the neural network and the expert reader, respectively. When testing with abnormal subjects represented by "Possible AD" cases, ROC areas for both the network and the expert were 0.81. The neural network out-performed discriminant analysis. It is concluded that PET has potential for the detection of abnormal brain function in dementing diseases, and that the combination of neural networks and PET is a useful diagnostic tool. Despite the low-resolution "view" afforded the neural network, its performance was nearly equivalent to that of an expert reader.

Adult

Neuroanatomic differences between dyslexic and normal readers on magnetic resonance imaging scans.

The areas of six bilateral brain segments in the right and left hemispheres, on a horizontal brain section, and the area of subdivisions of the corpus callosum, on a midsagittal brain section, were measured on magnetic resonance images obtained from 21 dyslexic and 29 control subjects. In the entire group, the frontal half of the horizontal brain section showed asymmetry, with the right side being larger, whereas posteriorly only the occipital polar segment was asymmetrical, with the left side being larger. Dyslexic subjects exhibited asymmetry, with the right side greater than the left side, in contrast to the relatively symmetrical pattern that is normally observed in the midposterior segment that corresponds to the angular gyrus. In the corpus callosum, dyslexic subjects were found to have a larger splenium than nondyslexic subjects, and dyslexic female subjects were found to have a larger splenium than dyslexic male subjects. Because transcallosal pathways connecting the left and right angular gyrus regions traverse through the splenium of the corpus callosum, the above findings in dyslexic subjects suggest an anatomic abnormality in the angular gyrus region.

Adult

Cerebrocerebellar relationship during behavioral activation: a PET study.

The effect of behavioral activation on cerebral and cerebellar glucose metabolism was studied in normal subjects when performing either a verbal memory task or a tactile somatosensory task. Each subject was also studied in a resting state control condition, either 1 h earlier or later than the activation task. Compared to the resting state, both tasks produced asymmetrical metabolic activation, which was opposite in direction within the cerebral and cerebellar hemispheres. In both tasks, the difference of activation of CMRglc in the right and left hemispheres in the cerebellum was negatively correlated with that in the sensory-motor region. This apparently coupled metabolic activation of one cerebellum and areas within the opposite cerebral hemisphere represents the inverse of the crossed cerebellar diaschisis phenomenon commonly observed when a vascular lesion affects one cerebral hemisphere and hypometabolism occurs in the opposite cerebellum. Because these correlations were selective and concordant with known anatomical connections, and were found in two different tasks, they suggest strong functional connections between these specific brain regions.

Aged

Positron emission tomographic studies during serial word-reading by normal and dyslexic adults.

Positron-emission tomography (PET) was used to study regional cerebral metabolic activity during oral reading in right-handed adult males with, and without a childhood and family history of developmental dyslexia. Significant group differences in normalized regional metabolic values were revealed in prefrontal cortex and in the lingual (inferior) region of the occipital lobe. Lingual values were bilaterally higher for dyslexic than normal readers. In contrast to the asymmetry observed in prefrontal and lingual regions in nondyslexic subjects during reading, the dyslexic pattern was more symmetric. These results demonstrate that individuals who suffered from familial developmental dyslexia as children, activate different brain regions during reading as adults, as compared to individuals without such childhood history.

Adult

Metabolic asymmetries in asymptomatic HIV-1 seropositive subjects: relationship to disease onset and MRI findings.

Fifteen male homosexual subjects (mean age 31.6 +/- 7.2 yr) who were asymptomatic, but HIV-1 seropositive (HIV+) were compared to 15 male age-matched HIV-1 seronegative (HIV-) subjects using resting PET/FDG studies and MR scans. Mean cerebral metabolic rates for glucose (mg/100 g/min) in the HIV+ and HIV- subjects were 7.7 +/- 1.7 and 7.0 +/- 2.1, (p = 0.44), respectively. An index of regional metabolic asymmetry for the whole brain was 5.8% +/- 3.2% in the HIV+ and 2.7% +/- 2.3% in the HIV- (p = 0.002), and the difference was most prominent in the prefrontal area. Significant asymmetries were found in 10/15 HIV+ subjects, primarily in prefrontal (7/15) and premotor (4/15) regions. MRI scans showed no abnormalities on clinical or quantitative evaluation in HIV+ subjects. Upon follow-up of HIV+ subjects over 18-40 mo, seven became symptomatic, of which two died. There was no relationship between the presence of PET scan abnormalities and earlier onset of symptomatic disease.

Adult

Oxidative C4-demethylation of 24-methylene cycloartanol by a cyanide-sensitive enzymatic system from higher plant microsomes.

Microsomes isolated from corn embryos (Zea mays) were shown to catalyse the C-4 monodemethylation of 28-[3H],24-methylene cycloartanol 1, leading to the corresponding 4 alpha-methyl sterol, cycloeucalenol 5. An enzymatic assay has been developed for the 4,4-dimethyl sterol 4-demethylase in higher plants. The demethylation process was shown to involve a 4-methyl, 4-hydroxymethyl derivative 2 which can be considered as the immediate metabolite of 1 by the 4-methyl oxidase. Compound 2 is further metabolized into 5 through a 4-methyl-4-carboxylic acid 3 and a 3-keto-4 alpha-methyl intermediate 4 which were identified. The conversion of 1 into 5 requires NADPH and molecular oxygen. The initial oxidative step was strictly dependent upon molecular oxygen, NADPH or NADH, and strongly inhibited by cyanide, whereas the overall process was completely insensitive to CO and to specific inhibitors of cytochrome P-450. It is concluded that in Zea mays microsomes, the C-4 demethylation of 1 results from a multistep process involving a terminal oxygenation system sensitive to cyanide which is distinct from cytochrome P-450 and in particular from that involved in the 14 alpha-demethylation of obtusifoliol.

Cholesterol

Sensitivity and specificity of positron emission tomography and magnetic resonance imaging studies in Alzheimer's disease and multi-infarct dementia.

Positron emission tomographic (PET) scans using [18F]-fluorodeoxyglucose and magnetic resonance imaging (MRI) scans were quantitatively analyzed for metabolic and structural abnormalities in normal subjects and patients classified as having Alzheimer's disease (AD), mixed dementia and multi-infarct dementia (MID) according to Hachinski ischemic scores. MRI-detected abnormalities in the periventricular white matter and in subcortical locations increased in incidence with age in normals and increased markedly in AD and especially in MID. Upper limits for the severity of these white matter lesions could be defined only for normal young and elderly subjects, but not for AD, mixed or MID patients. PET scan abnormalities occurred in about 90% of demented patients and in 54% of elderly and 34% of young normals. There was no characteristic pattern of abnormality that distinguished MID from AD patients. It is concluded that PET and MRI studies in demented patients are useful ancillary tests especially in evaluating the mild, questionably demented subject and for assessing the functional impact of structural disease.

Aged

Sensitivity of cerebral glucose metabolism to age, gender, brain volume, brain atrophy, and cerebrovascular risk factors.

In 76 normal volunteers studied by positron emission tomography, with [18F]fluorodeoxyglucose, CMRglu was significantly lower in the elderly as compared with young subjects and significantly higher in females relative to males. However, in 58 of these subjects who also had magnetic resonance imaging scans, age and gender were found to be unrelated to CMRglu, when the effects of brain volume and brain atrophy on CMRglu were partialed out using covariate analyses. Individually, brain volume was found to have a significant effect on CMRglu, explaining approximately 17% of the variability in CMRglu measures and brain atrophy explaining approximately 8% of the variance in CMRglu. Together these two measures accounted for approximately 21% of the variance. Cerebrovascular risk factors in normal subjects were not found to affect mean CMRglu or the variability of CMRglu measures. In this study almost 80% of the variance in CMRglu could not be explained by any of the factors that had been considered. This implies a lack of sensitivity of absolute values of global CMRglu to the mild effects of brain dysfunction. Although some of the unexplained variance is probably methodological in origin, physiological factors that are difficult to quantify, such as the state of arousal, are likely to be contributory as well.

Adult

Prealbumin-retinol-binding-protein-retinol complex in hemodialysis patients.

In hemodialysis (HD) patients, serum prealbumin (TBPA) is correlated to nutritional status and outcome despite usually elevated serum levels. The purpose of this work was to study the role of TBPA-retinol-binding-protein (RBP)-retinol complex changes in the elevation of serum TBPA in HD patients. Serum TBPA, RBP, and retinol were measured in 30 otherwise healthy HD patients (15 men, 15 women) and in 30 healthy volunteers (15 men, 15 women). The dependence of TBPA on RBP was studied by covariance and regression methods. TBPA (p less than 0.05), RBP (p less than 0.01), and retinol (p less than 0.05) were elevated in HD patients. Elevated TBPA was associated with a decrease of TBPA free from RBP (p less than 0.01). The decrease of free TBPA may explain the reduction of TBPA breakdown and its elevation in HD patients.

Adult