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Biomedical subjects

S Pascal

Publications and source records attributed to S Pascal.

At least 19 recordsLinked to original sources
PubMed2001

Hypotony maculopathy: improvement of visual acuity after 7 years.

PURPOSE: To describe a 79-year-old Caucasian male with a history of hypotony maculopathy for 7 years after cataract extraction with subsequent recovery of normal intraocular pressure and improvement of visual acuity. METHODS: Interventional case report. The patient developed an intraocular pressure ranging from 0 to 5 mm Hg after cataract surgery. He developed hypotony maculopathy, and the visual acuity declined to 20/200. On evaluation 7 years later, a superior cyclodialysis cleft was detected and treated with the argon laser. RESULTS: Closure of the cleft with argon laser was successful. The intraocular pressure stabilized at 17 to 20 mm Hg, and the visual acuity improved to 20/30. CONCLUSION: The development of hypotony maculopathy leads to impairment of visual acuity. This case demonstrates that visual acuity can improve after resolution of the maculopathy even after several years of hypotony.

Aged↗
PubMed2001

A study of quetiapine: efficacy and tolerability in psychotic adolescents.

OBJECTIVE: To study the effectiveness, safety, and tolerability of quetiapine in adolescents with psychotic disorders. METHODS: This study was an 8-week, open trial using quetiapine with 15 adolescents, ages 13-17 years, mean age 15.1 years, with a diagnosis of a psychotic disorder. Our primary instruments focused on psychotic symptomatology as measured by the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Positive and Negative Syndrome Scale (PANSS), and the Young Mania Rating Scale (YMRS). Other measures included adverse events, clinical laboratory tests, vital signs, electrocardiogram (ECG), extrapyramidal (EPS) measures, and ophthalmologic examination. RESULTS: Quetiapine significantly reduced psychotic symptoms as measured by the BPRS, PANSS, YMRS, CGI, and CGI Severity of Illness scale. The average weight gain was 4.1 kg. After correction for expected weight gain, the mean weight gain over the 8-week period was 3.4 kg. Prolactin and cholesterol remained unchanged. Trends were found for a decrease in T4 and an increase in thyroid-stimulating hormone. Common adverse effects were somnolence, agitation, drowsiness, and headache. No significant findings were noted on repeat ECGs, EPS measures, or ophthalmic examination. The final average treatment dose was 467 mg/day (range 300-800 mg/day). CONCLUSIONS: Quetiapine is suggested to be effective treatment of youths with psychotic disorders and to have a favorable side-effect profile.

Adolescent↗
PubMed2000

Pulmonary arterial hypertension in patients with sleep apnoea syndrome.

BACKGROUND: Pulmonary arterial hypertension (PAH) in patients with sleep apnoea syndrome (SAS) is classically ascribed to associated chronic obstructive pulmonary disease (COPD). The aim of this retrospective study was to evaluate the possible occurrence of PAH as a complication of SAS in patients without COPD. METHODS: Right heart catheterisation was performed in 44 patients with SAS and without COPD confirmed by polysomnography (apnoea index >5/h) admitted for the administration of nasal continuous positive airway pressure (CPAP). RESULTS: Precapillary PAH, defined as mean pulmonary arterial pressure of >20 mm Hg with pulmonary capillary wedge pressure <15 mm Hg, was observed in 12/44 (27%) patients with SAS. There were no significant differences in apnoea index between patients with (PAH+) and those without PAH (PAH-) (42.6 (26.3) versus 35.8 (21.7) apnoeas/h). The PAH+ group differed significantly from the PAH- group in the following respects: lower daytime arterial oxygen tension (PaO(2)) (9.6 (1.1) versus 11.3 (1.5) kPa, p=0.0006); higher daytime arterial carbon dioxide tension (PaCO(2)) (5.8 (0.5) versus 5.3 (0.5) kPa, p=0.002); more severe nocturnal hypoxaemia with a higher percentage of total sleep time spent at SaO(2) <80% (32.2 (28.5)% versus 10.7 (18.8)%, p=0.005); and higher body mass index (BMI) (37.4 (6) versus 30.3 (6.7) kg/m(2), p=0.002). The PAH+ patients had significantly lower values of vital capacity (VC) (87 (14)% predicted versus 105 (20)% predicted, p=0.005), forced expiratory volume in one second (FEV(1)) (82 (14)% predicted versus 101 (17)% predicted, p=0.001), expiratory reserve volume (40 (16)% predicted versus 77 (41)% predicted, p=0.003), and total lung capacity (87 (13)% predicted versus 98 (18)% predicted, p=0.04). Stepwise multiple regression analysis showed that mean pulmonary artery pressure (PAPm) was positively correlated with BMI and negatively with PaO(2). CONCLUSION: Pulmonary arterial hypertension is frequently observed in patients with SAS, even when COPD is absent, and appears to be related to the severity of obesity and its respiratory mechanical consequences.

Blood Gas Analysis↗
PubMed1996

Conformational trapping in a membrane environment: a regulatory mechanism for protein activity?

Functional regulation of proteins is central to living organisms. Here it is shown that a nonfunctional conformational state of a polypeptide can be kinetically trapped in a lipid bilayer environment. This state is a metastable structure that is stable for weeks just above the phase transition temperature of the lipid. When the samples are incubated for several days at 68 degrees C, 50% of the trapped conformation converts to the minimum-energy functional state. This result suggests the possibility that another mechanism for functional regulation of protein activity may be available for membrane proteins: that cells may insert proteins into membranes in inactive states pending the biological demand for protein function.

Magnetic Resonance Spectroscopy↗
PubMed1995

Clinicopathologic study of probable Alzheimer disease: assessment of criteria for excluding cerebrovascular disease.

The National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related Disorders Association criteria for probable Alzheimer disease (AD) require exclusion of non-AD dementia-producing conditions but do not specify how the non-AD conditions are to be identified. We addressed this issue for the case of cerebrovascular disease (CVD) by defining exclusion rules based on commonly described clinical features: (a) history of strokelike episodes; (b) history of stepwise cognitive decline; (c) focal deficits on neurological examination; and (d) evidence of significant CVD on neuroimaging. We applied these rules retrospectively to clinical records for 92 cognitively impaired patients who otherwise met criteria for probable AD and whose brains were subsequently available for postmortem examination. We used Fisher's exact test to assess the effectiveness of the exclusion rules in predicting the presence of CVD on autopsy. Prediction was better than chance when all four clinical features were used together (p = 0.0008) and when the stepwise decline or neuroimaging criteria were used alone (p = 0.03 and p = 0.05, respectively). Overall, the CVD exclusion rules were deficient because of low accuracy (50.0%) and low sensitivity (52.6%). These results support provisional use of the CVD criteria chosen for this study but suggest that modifications are needed for acceptable diagnostic accuracy and sensitivity to be achieved.

Alzheimer Disease↗
PubMed1994

Plant sterol biosynthesis: identification of a NADPH dependent sterone reductase involved in sterol-4 demethylation.

Microsomes obtained from maize embryos were shown to catalyze the reduction of various sterones to produce stereoselectively the corresponding 3 beta-hydroxy derivatives. Enzymatic assay conditions have been developed to characterize this reduction step and the kinetics of the microsomal system has been established. Sterone reduction shows exclusive dependence on NADPH and is inactive with NADH. It is not sensitive to the azole inhibitors pyrifenox, ketoconazole, and itraconazole nor to phenobarbital nor pyrazole. Based on these coenzyme requirements and inhibitor susceptibility, and according to the common pattern of their classification, the maize microsomal sterone-reducing enzyme belongs to the family of ketone reductases. From a series of incubations with natural or synthetic sterones, the substrate specificity of the reduction at C-3 was determined. Our data indicate particularly that 4 alpha-methyl-9 beta,19-cyclo-C30-sterones and 4-desmethyl-delta 7-C27- or C30-sterones are preferentially reduced, while 4,4-dimethyl-C30- or C31-sterones react poorly. The results support the conclusion that the reductase activity identified is a constitutive component of the microsomal sterol 4-demethylation complex recently identified in photosynthetic organisms (S. Pascal et al., 1993, J. Biol. Chem. 268, 11639). They are consistent with the conclusion that 4 alpha-methylsterones are demethylation products of 4,4-gem-dimethylsterols rather than early intermediates in the 4 alpha-monomethyl-sterols-4-demethylation process.

Alcohol Oxidoreductases↗
PubMed1993

Plant sterol biosynthesis. Identification and characterization of two distinct microsomal oxidative enzymatic systems involved in sterol C4-demethylation.

Membrane-bound enzymatic systems obtained from maize embryos that catalyze the oxidative C4-monodemethylation of 4,4-dimethyl- and 4 alpha-methylsterols have been investigated. Enzymatic assay conditions have been developed for the first time to detect the C4-monodemethylated products formed. The properties of the microsomal systems have been established for co-factor requirements and kinetics. The demethylation process has been interrupted to demonstrate the formation of stable, oxygenated intermediates. In addition to the 3-keto and 3 beta-hydroxy-4-monodemethylated products formed, three new sterols have been identified. 3 beta-Hydroxy-4 beta,14 alpha-dimethyl-5 alpha-ergosta-9 beta,19-cyclo-24(24(1))-en-4 alpha-hydroxy methyl was identified for the first time as the immediate metabolite of 24-methylenecycloartanol by 4 alpha-methyl oxidase in addition to 3 beta-hydroxy-4 beta,14 alpha-dimethyl-5 alpha-ergosta-9 beta,19-cyclo- 24(24(1))-en-4 alpha-carboxylic-acid and 3 beta-hydroxy-5 alpha-stigmasta-7,24(24(1))-dien-4 alpha-carboxylic-acid, intermediates involved respectively in the oxidative demethylation of 24-methylenecycloartanol and 24-ethylidenelophenol. Proton nuclear magnetic resonance studies of enzymatically produced 3 beta-hydroxy-4 beta,14 alpha-dimethyl-5 alpha-ergosta-9 beta,19-cyclo-24(24(1))en-4 alpha-carboxylic acid indicate that the 4 alpha-methyl group of 24-methylenecycloartanol is oxidized and subsequently removed during its enzymatic conversion to cycloeucalenol. From a series of incubations with 25 natural or synthetic 4,4-dimethyl and 4 alpha-methylsterols, a high degree of substrate specificity for the oxidation at C4 of 4,4-dimethyl- and 4 alpha-methylsterols was determined. Our results indicate that oxidation of the 4 alpha-methyl group of the 4,4-geminal dimethylsterols requires the more flexible and presumably bent conformation of 9 beta,19-cyclopropylsterols and the absence of a delta 24(25) unsaturation, whereas the rigid planar conformation of delta 7-unsaturated sterols favors oxidation of 4 alpha-methylsterols. Distinct strict structural requirements for the oxidation of 4,4-dimethyl- and 4 alpha-methylsterols and different sensitivity toward cyanide ions and 3 beta,5 alpha,6 alpha-stigmastatriol, a novel inhibitor of 4 alpha-methylsterol C4 oxidase activity, are consistent with the conclusion that two distinct oxidative systems are involved in the removal of the first and second C4-methyl group of phytosterol precursors. Moreover, the present study directly establishes that during the conversion of cycloartenol to phytosterol one C4 dealkylation occurs before the removal of the 14 alpha-methyl group.

Indicators and Reagents↗
PubMed1993

[Cardio-respiratory complications of sleep apnea in obese patients].

The cardio-respiratory complications of sleep apnea syndrome have been prospectively assessed in 60 patients with massive obesity and free of chronic obstructive lung disease while the associated cardiovascular diseases and the alterations of pulmonary function were taken into account. These cardio-respiratory complications were observed only in patients with a number of apneas per hour of sleep greater than 20. The sleep apneas induced nocturnal hypoxemia that is frequently severe and independently correlated to the apnea index, diurnal hypoxemia and hypercapnia that are usually moderate, and presumably left ventricular hypertrophy that is not related to the development of daytime hypertension. However the nocturnal apneas were not associated with the development of an impairment of right or left ventricular function, or with the occurrence of cardiac arrhythmias or conduction disturbances. The absence of severe cardiac complications in this study may be related to the fact that the patients were relatively young and that the sleep apnea syndrome was diagnosed at an early stage of evolution. The findings of this study could help to define a more rationale approach in several therapeutic indications of sleep apnea syndrome.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗