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Biomedical subjects

C Michel

Publications and source records attributed to C Michel.

At least 109 records · Page 6Linked to original sources

Prevalence of histological beta2-microglobulin amyloidosis in CAPD patients compared with hemodialysis patients.

BACKGROUND: The prevalence of beta2-microglobulin amyloidosis (Abeta2m) in patients on continuous ambulatory peritoneal dialysis (CAPD) is unknown. METHODS: We prospectively obtained a median of 2 (range 1 to 4) joint samples from 26 CAPD patients aged 44 to 93 (median 73) years at post-mortem evaluation after 4.5 to 126 (median 27) months solely on CAPD (N = 19) or primarily on CAPD (that is, < or = 10% and < or = 1 year of renal replacement therapy time on other modalities; N = 7). The diagnosis of Abeta2m rested on Congo red staining (typical birefringence) and positive immunostaining of amyloid deposits by a monoclonal anti-beta2m antibody. RESULTS: Abeta2m was diagnosed in 8 of 26 patients (31%). Prevalence ranged from 20% (2 of 10 patients) within < or = 24 months CAPD to 30% (3 of 10 patients) after 24 to 48 months and 50% (3 of 6 patients) after 49 to 126 months (P = 0.11). The prevalence of Abeta2m was similar in patients without or with one or more peritonitis episodes. No significant difference in prevalence (P = 0.118) was found between CAPD patients (8+/26; 31%) and hemodialysis patients (13+/26; 50%) carefully matched for time on dialysis and age at the onset of dialysis. CONCLUSIONS: The prevalence of histological Abeta2m reaches 31% after a median duration of 27 months of CAPD. This prevalence is not significantly different from that observed in a group of HD patients matched for age and dialysis duration.

Adult↗

[Visual perception of movement. A normative study].

BACKGROUND: A battery of tests has been developed to better define the variety of defects which can occur in the process of visual perception of motion. METHODS: The tests assessed the perception of 1) coherent motion, in each of the four cardinal directions; (2) form from motion; (3) flow in depth; and (4) motion of a target moving in depth, within or without an optic flow surround. A normative study was conducted with 34 subjects, 21 to 69 years of age. RESULTS: Recognition of form from motion was better with upwards than with downwards motion. Perception of motion in depth was better with backward than forwards motion. The presence of an optic flow altered the perception of a motion in depth. CONCLUSION: The recognition of form from motion demonstrated an asymmetry in threshold between the upward and downward movements. This asymmetry did not occur with global coherent motion, thus reflecting the variety of mechanisms involved in the visual process of motion. Moreover, alteration of perception of motion in depth within an optic flow reflected background effect.

Adult↗

Physical activity, skeletal muscle beta-adrenoceptor changes and oxidative metabolism in experimental chronic heart failure.

In chronic heart failure (CHF), changes in sympathetic nervous activity and skeletal muscle metabolism contribute to a limitation in the capacity for exercise. The aim of this study was to investigate the potential relationships between physical deconditioning, skeletal muscle beta-adrenoceptor (beta-AR) characteristics and muscle metabolic changes in rats with coronary ligation-induced experimental CHF. Muscle beta-AR and norepinephrine levels were assessed in rats with CHF that had been treated with propranolol at 28 mg/kg/day and compared with rats with CHF that had not been treated and those that had undergone sham operations. The soleus muscle was investigated because of its predominantly oxidative fibre-type composition. Measurements of spontaneous locomotion activity were carried out using telemetry. After 85 days, muscle energetic phosphate levels were assessed using 31P-magnetic resonance spectroscopy. The phosphocreatine resynthesis rate was decreased in the untreated CHF rats (15 +/- 3 vs 33 +/- 5 mmol L-1 min-1 in the sham-operated rats, p < 0.05), but this had been partially reversed in the rats given propranolol (22 +/- 3 mmol L-1 min-1, non-significant (NS) when compared with the sham-operated rats). Spontaneous activity did not differ among the three groups of animals. Soleus beta-adrenoceptor density was decreased in rats with CHF (8.8 +/- 3.0 fM/mg of protein vs 22.0 +/- 7.0 fM/mg of protein in the sham-operated rats, p < 0.05) and normalized in the propranolol-treated rats (31.9 +/- 7.0 fM/mg of protein, NS vs the sham-operated rats; p < 0.05 vs the untreated rats with CHF). Unchanged spontaneous activity in the rats with CHF suggests that physical deconditioning could not account for the muscle metabolic changes. Changes in skeletal muscle energy metabolism were accompanied by changes in beta-AR density, occurring in typically oxidative beta-AR-rich muscles, reversible after beta-blocker therapy and therefore suggestive of beta-AR downregulation.

Adrenergic beta-Antagonists↗

Motor perseverations: a function of the side and the site of a cerebral lesion.

Motor perseverations are commonly thought to be a sign of frontal lobe lesions, although they may also occur following lesions outside the frontal lobes. Moreover, differences in the type and frequency of motor perseverations between the two cerebral hemispheres have been suggested. Recurrent perseverations (repetition of a previous response to a subsequent stimulus) and continuous perseverations (abnormal prolongation of a current activity) are two different aspects of motor intentional disorders. The former have been associated with left hemispheric lesions, and the latter with right hemispheric lesions. To test this hypothesis, we examined 42 patients with single cerebral lesions of different locations: 22 right hemispheric (7 frontal and 15 extrafrontal) and 20 left hemispheric lesions (8 frontal and 12 extrafrontal), and healthy controls with a graphic task, allowing for analysis of these two types of motor perseverations. We found that (i) both types of perseverations increased significantly for all groups of patients compared to normal controls, except for recurrent perseverations in patients with right posterior lesions, (ii) there was no significant dissociation between the type of perseverations and the side of lesions, and (iii) there was a significant interaction between the type of perseveration, frontal versus extrafrontal location, and the side of a lesion, which is based on the tendency for recurrent perseverations to be increased in left posterior and right frontal lesions, and decreased in left frontal and right posterior lesions, as compared to continuous perseverations. These findings cast doubt about the predominant role of the frontal lobes for motor perseverations, but support the idea of hemispheric specialization in motor control which is, however, more complex than previously thought.

Adult↗

[Adventicial cyst of the popliteal artery].

In a 42-year-old man with intermittent calf claudication, cystic adventitial disease of the popliteal artery was demonstrated by 3D CT. Cystic mass was seen to be compressing the arterial lumen. The diagnosis of cystic adventitial was confirmed by surgery. Compared with color doppler sonography, MR Imaging, 3D CT provides additional useful anatomic information concerning disease of the popliteal artery, usually gained only with sonography or arteriography.

Adult↗

Nitrogen-13-ammonia and oxygen-15-water estimates of absolute myocardial perfusion in left ventricular ischemic dysfunction.

UNLABELLED: Measurements of resting myocardial blood flow (MBF) in patients with chronic left ventricular ischemic dysfunction by 15O-water with 13N-ammonia and PET have yielded conflicting results. The aim of this study was to perform a head-to-head comparison of both tracers in the same patient population and to answer the question of whether distinctive tracer properties account for differences in estimates of MBF in chronically dysfunctional myocardium by both tracers. METHODS: A total of 30 patients with chronic dysfunction of the anterior myocardial wall due to significant left anterior descending coronary artery disease underwent PET measurements of absolute MBF in the anterior wall by use of 15O-water and 13N-ammonia before coronary revascularization by either coronary artery bypass graft (n = 24) or percutaneous transluminal coronary angioplasty (n = 6). Improvement of regional contractile function was assessed by two-dimensional echocardiography at a mean of 7.5 +/- 2.1 mo after revascularization. As judged from the changes in anterior myocardial wall motion after revascularization, patients were considered to have either reversibly (n = 16) or persistently (n = 14) dysfunctional myocardium. Estimates of MBF by 15O-water and 13N-ammonia, obtained in every patient before revascularization, were compared among the two patient groups by use of previously validated methods. RESULTS: With 13N-ammonia, resting regional MBF was significantly higher in reversibly as opposed to persistently dysfunctional segments [84 +/- 8 versus 48 +/- 6 ml (min x 100 g)(-1), mean +/- s.e.m., p < 0.01]. By contrast, no such difference was found when using 15O-water to measure MBF [74 +/- 6 versus 86 +/- 9 ml (min x 100 g)(-1), p = ns]. This was mainly due to the fact that the perfusable tissue fraction (PTF), a fitted parameter of the 15O-water model, was significantly higher in reversibly as opposed to persistently dysfunctional segments (0.63 +/- 0.03 versus 0.50 +/- 0.03, p < 0.05). As a consequence, the 15O-water perfusable tissue index (PTI), which is the ratio of the PTF to the anatomical tissue fraction, was greater in reversibly dysfunctional as opposed to persistently dysfunctional segments (1.07 +/- 0.07 versus 0.79 +/- 0.05, p < 0.01). CONCLUSION: This study demonstrates significant differences in MBF estimates between 15O-water and 13N-ammonia in chronically dysfunctional ischemic myocardium. Our results indicate that the 15O-water method yields higher absolute MBF values than the 13N-ammonia approach. Our results also support the use of PTI as a marker of myocardial tissue viability.

Adult↗

Conversion of dihydroceramide to ceramide occurs at the cytosolic face of the endoplasmic reticulum.

Dihydroceramide desaturase is responsible for the introduction of the 4,5-trans double bond into ceramide. Here, we describe the localization of this enzyme in the endoplasmic reticulum (ER) using ER- and Golgi-enriched fractions from rat liver. Furthermore, enzyme topology was studied. Mild proteolysis of ER-derived vesicles under conditions which assure membrane integrity (latency of mannose 6-phosphatase was at least 91%) resulted in an up to 90% inactivation of dihydroceramide desaturase activity. This indicates a cytosolic orientation of dihydroceramide desaturase activity in the ER membrane.

Animals↗

Characterization of ceramide synthesis. A dihydroceramide desaturase introduces the 4,5-trans-double bond of sphingosine at the level of dihydroceramide.

Ceramide (N-acylsphingosine) biosynthesis has been proposed to involve introduction of the 4,5-trans-double bond of sphingosine after synthesis of dihydroceramide (i.e. N-acylsphinganine). For the first time, the in vitro conversion of dihydroceramide to ceramide has been demonstrated using rat liver microsomes and N-[1-14C]octanoyl-D-erythro-sphinganine (st-H2Cer) and either NADH or NADPH as co-substrate; the apparent Km values for st-H2Cer and NADH were 340 and 120 microM, respectively. Molecular oxygen is required for enzymatic activity, and cyanide, divalent copper, as well as antibodies raised against cytochrome b5 are inhibitory, which suggests that this enzyme should be named dihydroceramide desaturase based on these similarities with the mechanism of delta9-desaturase (stearoyl-CoA desaturase). Factors that influenced the activity of dihydroceramide desaturase include the alkyl chain length of the sphingoid base (in the order C18 > C12 > C8) and fatty acid (C8 > C18); the stereochemistry of the sphingoid base (D-erythro- > L-threo-dihydroceramides); the nature of the headgroup, with the highest activity with dihydroceramide, but some (approximately 20%) activity with dihydroglucosylceramide, however); and the ability to utilize alternative reductants (ascorbic acid could substitute for a reduced pyridine nucleotide, but was inhibitory at higher concentrations). Dihydroceramide desaturase was inhibited by dithiothreitol, which suggests that it might be possible to alter ceramide synthesis by varying the thiol status of hepatocytes. Consistent with this hypothesis, when rat hepatocytes were cultured in varying concentrations of N-acetylcysteine (5 and 10 mM), there was a decrease in the relative incorporation of [14C]serine into [14C]ceramide. These studies have conclusively established the pathway of ceramide synthesis via desaturation of dihydroceramide and have uncovered several properties of this reaction that warrant further consideration for their relevance to both sphingolipid metabolism and signaling.

Animals↗

[Complications of treatment by dialysis].

Only 30 years ago, the inevitable short-term outcome in patients with end-stage renal disease was death. Today, the widespread development of dialysis-transplantation programs and extended indications have totally revolutionalized the situation, yet despite great progress, quality of life and life expectancy remain inferior in uremic patients. Cardiovascular disease is the main cause of mortality, 50% of all deaths in chronic dialysis patients resulting from complex mechanisms leading to left ventricular hypertrophy, coronary artery disease and atheroma of the great vessels. A large number of factors are involved in disease progression including age, genetic factors and personal health status prior to dialysis as well as the nature of the initial renal disease and dialysis-related metabolic and cardiac output disorders among others. Morbidity is also higher in dialysis patients, mainly due to altered blood volume and pressure which respond variably to treatment. Other conditions include rythm disorders, diabetes, potassium depletion, hypoxemia. Angina is frequent and ischemia can occur in several territories, including the mesentery as reported by Hachache et of in this issue of La Presse Médicale. Prognosis depends heavily on events which occur prior to dialysis and thus on close collaboration between the nephrology team, the family physician and other specialists who must coordinate their efforts to identify early curable renal diseases and correctly manage moderate disease to prevent progression and avoid emergency dialysis situations.

Cardiovascular Diseases↗

Brain energy metabolism in early blind subjects: neural activity in the visual cortex.

As an attempt to better understand the metabolic basis for the previously reported increases in glucose metabolism in the visual cortex of congenitally blind subjects, cerebral blood flow, oxygen consumption and glucose utilization were investigated with multitracer positron emission tomography. Measurements were carried out in three subjects who became blind early in life and in three age-matched blindfolded controls. Regional analysis of cerebral blood flow, metabolic rates for oxygen and glucose utilization revealed that these parameters were relatively higher in the visual cortex in case of early blindness (109.7 +/- 2.4%; 114.3 +/- 1.5%; 118.0 +/- 5.5%, respectively) than in controls (98.1 +/- 3.9%; 108.6 +/- 3.6%; 105.2 +/- 4.8%). There were slight differences, albeit statistically not significant, between early blind and control subjects in terms of oxygen-to-glucose metabolic ratios. The relatively preserved stoichiometry in the visual areas of blind subjects points to the lack of variation in the yield of glucose oxidation in this cortex. Those observations suggest that the high level of energy metabolism disclosed in early blind visual cortex is related to neural activity.

Adult↗

Anonymous HIV testing using home collection and telemedicine counseling. A multicenter evaluation.

BACKGROUND: Home human immunodeficiency virus (HIV) testing has been proposed as an alternative to conventional HIV testing. Despite debate over HIV type 1 (HIV-1) home test systems, these concerns have not to our knowledge been previously studied. OBJECTIVE: To evaluate the safety and efficacy of the Home Access Health Corp (Hoffman Estates, Ill) HIV-1 test system compared with traditional HIV-1 testing with venous blood. METHODS: A total of 1255 subjects were studied prospectively in a blinded, subject-as-control evaluation at 9 outpatient clinics using intent-to-treat analysis. Subjects were provided a home collection kit (Home Access Health Corp) to collect their own finger-stick blood spot samples for laboratory analysis. Subjects received pretest counseling by telephone and their comprehension was subsequently assessed. Subject-collected blood spot samples were compared with professionally drawn blood spot samples for adequacy (sufficient for completing the Food and Drug Administration-endorsed testing) and with venous samples for accuracy. Subjects called 3 days later for anonymous results and posttest counseling. Device safety was evaluated based on adverse events incidence. Subject comprehension of HIV information was measured. RESULTS: Subject-collected blood spot sample results were in complete agreement with venous blood sample results, demonstrating 100% sensitivity and 100% specificity compared with venous controls. Ninety-eight percent of subjects obtained testable blood spot specimens compared with phlebotomists. Following pretest counseling, subjects answered 96% of HIV risk questions correctly. There were no significant adverse events. CONCLUSION: Anonymous HIV-1 home collection kits with pretest and posttest telephone counseling can provide a safe and effective alternative to conventional venous HIV-1 antibody testing.

Adult↗

Cholinergic neurotransmission has different effects on cerebral glucose consumption and blood flow in young normals, aged normals, and Alzheimer's disease patients.

Cerebral blood flow (CBF) and glucose consumption (GC) are both tracers of brain metabolic activity used to image the human brain in vivo. To know if both tracers reacted in the same manner when brain cholinergic neurotransmission was activated, CBF and GC were measured in young normals (YN), aged normals (AN), and Alzheimer's Disease patients (AD) using positron emission tomography (PET), H2 15O, and 18F-FDG. Each subject was studied twice, under placebo and physostigmine, in randomized order and blind fashion using the maximal tolerated dose of physostigmine individually determined. Under physostigmine CBF increased significantly (P = 0.0007) in posterior regions of the cerebral cortex and in the subcortical structures. Inversely, GC was decreased significantly in most regions. The largest decrease was seen in the prefrontal region of the cerebral cortex (P < 0.0001). Significant regional decreases were registered in all three groups of subjects, but were larger in AD than in controls. Looking at the absolute values of prefrontal cortex metabolism we found no correlation (r = 0.04) between the responses of CBF and GC. After normalization of the regional values for the mean we found a significant positive correlation between the responses of CBF and GC (r = 0.71, P < 0.0001). These findings suggest two components in the CBF response to physostigmine: one metabolic, depressive, and regional which follows the GC response; and one vascular, larger, diffuse, and opposite in direction to the metabolic component. These results have implications for the interpretation of CBF values as tracer of brain metabolic activity when brain cholinergic neurotransmission is manipulated.

Adult↗

Relationship between left ventricular hypertrophy, myocardial contractility, and load conditions in hemodialysis patients: an echocardiographic study.

Left ventricular hypertrophy (LVH) is common and is an independent cardiac risk factor in dialysis patients. The aim of this study was to assess hemodynamic determinants of LVH and, more particularly, the relationship between left ventricular mass, myocardial contractility, and load conditions. Eighty dialysis patients aged 51 +/- 15 years were prospectively studied by echocardiography. LVH was detected in 62 patients (78%). Left ventricular mass was significantly correlated to both end-diastolic volume (r = 0.54; P < 0.001) and end-systolic stress/end-systolic volume, an index of contractility (r = -0.66; P < 0.001), but not to systolic blood pressure or end-systolic stress, both indexes of afterload. Thus, in dialysis patients, the degree of LVH is significantly correlated with the severity of both left ventricular dilatation and contractile myocardial failure, but not with left ventricular afterload.

Adolescent↗

[Protective effect of labetalol on cardiovascular consequences of brain death in the swine].

OBJECTIVE: Assessment of the preventive effect on cardiovascular changes following experimental brain death (BD) in the pig by pretreatment with labetalol, an alpha and beta adrenoreceptor blocking agent. STUDY DESIGN: Experimental study. ANIMALS: Ten 25-35 kg domestic pigs allocated either in the control group (n = 5) or the labetalol group (n = 5). METHODS: BD was achieved in anaesthetized animals by the rapid inflation of a Foley catheter inserted into the sub-dural space. In the labetalol group, the agent (total: 10 +/- 3 mg.kg-1) was administered immediately before BD and thereafter over a 20-min period, in order to maintain haemodynamic parameters at control values. The following haemodynamic data were recorded over a 3 hour period after BD: heart rate (HR), dP/dtmax, mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO) and left anterior descending coronary artery blood flow (CBF). Afterwards, a dynamic loading test with 500 mL of dextran over 20 min was performed. RESULTS: In the control group, BD elicited a significant increase in HR (from de 96 +/- 9 to 176 +/- 11 b.min-1), dP/dtmax (from 1,960 +/- 123 to 4,904 +/- 930 mmHg.s-1), MAP (from 88 +/- 5 to 119 +/- 11 mmHg), CO (from 2.4 +/- 0.2 to 3.6 +/- 0.7 L.min-1) and CBF (from 45 +/- 6 to 73 +/- 7 mL.min-1) respectively. Apart from a slight increase in HR and a significant increase in CBF (from 34 +/- 4 to 55 +/- 6 mL.min-1), no other modifications occurred in the labetalol group. Following volume expansion, the labetalol group animals experienced a significant increase in CO (from 2.3 +/- 0.3 to 3.7 +/- 0.2 L.min-1), dP/dtmax (from 1,400 +/- 91 to 2,100 +/- 212 mmHg.s-1) and MAP (from 55 +/- 5 to 70 +/- 5 mmHg). In the opposite, a significant decrease in dP/dtmax (from 1,645 +/- 450 to 628 +/- 152 mmHg.s-1) occurred in the control group. CONCLUSION: The protective effect of labetalol confirms the role played by the activation of the cardiac sympathetic nervous system in the cardiocirculatory changes following BD.

Adrenergic alpha-Antagonists↗

GABA(A) receptors containing the alpha4-subunit: prevalence, distribution, pharmacology, and subunit architecture in situ.

Recombinant GABA(A) receptors, expressed from alpha-, beta-, and gamma2-subunits, are diazepam-insensitive when the alpha-subunit is either alpha4 or alpha6. In situ, diazepam-insensitive receptors containing the alpha6-subunit are almost exclusively expressed in the granule cell layer of the cerebellum. However, diazepam-insensitive receptors are also expressed in forebrain areas. Here, we report on the presence of diazepam-insensitive GABA(A) receptors in various brain areas containing the alpha4-subunit. GABA(A) receptors immunoprecipitated with a newly developed alpha4-subunit-specific antiserum displayed a drug binding profile that was indistinguishable from those of alpha4beta2gamma2-recombinant receptors and diazepam-insensitive [3H]Ro 15-4513 binding sites in rat brain membranes. In addition, alpha4-subunit containing receptors and forebrain diazepam-insensitive receptors are present at comparably low abundance in rat brain and exhibit virtually identical patterns of distribution. Analysis of the subunit architecture of alpha4-subunit containing receptors revealed that the alpha4-subunit contributes to several receptor subtypes. Depending on the brain region, the alpha4-subunit can be coassembled with a second type of alpha-subunit variant being alpha1, alpha2, or alpha3. The data demonstrate that native receptors containing the alpha4-subunit are structurally heterogeneous, expressed at very low abundance in the brain, and display the drug binding profile of diazepam-insensitive [3H]Ro 15-4513 binding sites. Pharmacologically, these receptors may contribute to the actions of nonclassical ligands such as Ro 15-4513 and bretazenil.

Animals↗