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Biomedical subjects

Philippe Robert

Publications and source records attributed to Philippe Robert.

At least 37 records · Page 2Linked to original sources

Novelty seekers and impulsive subjects are low in morningness.

The bipolar dimension of morningness-eveningness refers to the preferred times of day for achieving various activities (i.e. the phase of the circadian clock). It is validated from a biological point of view, associated with at least one gene and heritable through an epistatic mechanism. It has been used as a proxy to study the relationships between the circadian system, personality and psychopathology: there is a correlation between the evening orientation and depression, extraversion and, probably, impulsivity. Furthermore, there is a possible relationship with temperament in children as theorized by Thomas and Chess. In this paper, we expanded on the hypothesis that impulsive subjects are low in morningness by performing a factor analysis of the Composite Scale of Morningness, Cloninger's temperament and character inventory, and Spielberger's trait anxiety inventory in a sample of 129 males. The results can probably be extended to women. Morningness is negatively correlated with novelty seeking (which includes an impulsivity facet), positively correlated with persistence, and independent of character dimensions and trait anxiety. Future research may focus in the involvement of the circadian system in these personality dimensions and facets, and the benefits of adding chronotherapic manipulations in the treatment of the personality disorders.

Adolescent↗

Dark lumen magnetic resonance colonography in a rodent polyp model: initial experience and demonstration of feasibility.

PURPOSE: We sought to assess dark lumen magnetic resonance (MR) colonography for the detection of colon polyps in a rodent model with histology as the gold standard. MATERIAL AND METHODS: Fourteen male Wistar rats were subjected to carcinogenic N-methyl-N'-nitro-N-nitrosoguanidine at the age of 4 months to induce colon neoplasms. MR imaging was performed after a time interval of 1 year. Preparation and data acquisition was performed with the animals under full anesthesia. After a body-warm saline enema images were acquired on a clinical 1.5-T whole-body MR system using a standard extremity coil. Plain and contrast-enhanced (0.3 mmol/kg; Gd-DOTA; Dotarem, Guerbet, France) 3-dimensional T1-weighted gradient recall echo images were acquired. Two radiologists analyzed the MR data sets in consensus for lesion depiction. Contrast uptake in colonic wall and polyps was quantitatively assessed by signal-to-noise ratio and contrast-to-noise ratio measurements and compared using a Wilcoxon-Mann-Whitney U test with statistical significance at a P value < 0.05. Finally, all animals were killed, and the MR imaging results were compared with pathologic findings. Sensitivity and specificity were calculated. RESULTS: By pathology, a total of 15 polyps were found in 9 of 14 rats. MR colonography detected 13 of 15 polyps measuring between 4 and 11 mm (mean 7 +/- 0.6 mm) in 8 of 9 animals, resulting in a sensitivity and specificity of 0.87 and 1.0, respectively. Compared with the precontrast data, all polyps showed a statistically significant increase in signal-to-noise ratio (78.2 +/- 6.3 to 167.4 +/- 17.7) and contrast-to-noise ratio (45.4 +/- 5.2 to 124.6 +/- 11.2). CONCLUSION: MR colonography with a dark colon lumen and a bright, contrast-enhanced colon wall appears well suited for the detection of colonic lesions in a rodent model.

Animals↗

Evaluation of the Two-Way Communication Checklist as a clinical intervention. Results of a multinational, randomised controlled trial.

BACKGROUND: Patients and doctors often have divergent views on care needs. AIMS: To examine whether providing patients with an opportunity to identify and discuss their needs would improve communication and induce changes in care. METHOD: Patients with schizophrenia (n=134) were randomly allocated to either standard care or use of the Two-Way Communication Checklist (2-COM). Before seeing their clinician for a routine follow-up, participants in the active intervention group were given 2-COM, a list of 20 common needs, and told to indicate those areas they wanted to discuss with their doctor. Outcomes were assessed immediately and again after 6 weeks. RESULTS: Using 2-COM induced a stable improvement of patient-reported quality of patient-doctor communication (B=0.33, P=0.031), and induced changes in management immediately after the intervention (OR=3.7, P=0.009; number needed to treat, 6). Treatment change was more likely inpatients with more reported needs, and needs most likely to induce treatment change displayed stronger associations with non-medication than with medication changes. CONCLUSIONS: A simple intervention to aid people in discussion of their needs results in improved communication and changes in management.

Adult↗

Effect of subthalamic nucleus stimulation on obsessive-compulsive disorder in a patient with Parkinson disease. Case report.

The authors report on a patient with Parkinson disease (PD) and severe obsessive-compulsive disorder (OCD), in whom bilateral stimulation of the subthalamic nucleus (STN) was used to treat both PD and OCD symptoms. This 49-year-old man had displayed symptoms of PD for 13 years. Progressively, his motor disability became severe despite optimal medical treatment. In parallel, he suffered severe OCD for 16 years, with obsessions of accumulation and compulsions of gathering and rubbing that lasted more than 8 hours per day. Bilateral high-frequency STN stimulation was performed to treat motor disability. After surgery (at 1-year follow up), motor and OCD symptoms were dramatically improved. The pre- and postoperative Yale-Brown Obsessive-Compulsive Scale scores were 32 and 1, respectively. No additional antiparkinsonian drugs were administered. This case and other recent reports indicate that OCD symptoms can be improved by deep brain stimulation, a finding that opens new perspectives in the surgical treatment of severe and medically intractable OCD.

Electric Stimulation Therapy↗

Wavelength modulation spectroscopy: combined frequency and intensity laser modulation.

A theoretical model of wavelength modulation spectroscopy that uses a laser diode on a Lorentzian absorption line is presented. This theory describes the general case of a current-modulated semiconductor laser, for which a combined intensity and frequency modulation with an arbitrary phase shift occurs. On the basis of this model, the effect of several modulation parameters on the detected signals is evaluated. Experimental signals measured on an absorption line of CO2 by use of a 2-microm distributed-feedback laser are also presented and validate this analysis. These experimental results agree with the calculated signals, confirming the relevance of the model.

Journal Article↗

Distributed measurement of chromatic dispersion by four-wave mixing and Brillouin optical-time-domain analysis.

A new nondestructive method for measuring the spatial distribution of chromatic dispersion along an optical fiber is presented. It is based on using Brillouin optical time-domain analysis to probe the power distribution of the four-wave mixing generated by two continuous-wave lasers. The results obtained prove that this new method is capable of providing better performance than comparable techniques. Furthermore, sensing the variations of Brillouin gain maximum produces additional information about the fiber, such as presence of strain and concentration of GeO2.

Journal Article↗

Biomolecular interactions between human recombinant beta-MyHC and cMyBP-Cs implicated in familial hypertrophic cardiomyopathy.

OBJECTIVE: Cardiac myosin-binding protein C (cMyBP-C) is a component of sarcomere that contains at least three putative myosin-binding sites. Mutations in its gene are implicated in familial hypertrophic cardiomyopathy (FHC) and most of them are predicted to produce C-terminal truncated cMyBP-Cs. The aim of the present study was to analyze whether cMyBP-C truncated mutants resulting from FHC mutations interact in vitro with human beta-MyHC. METHODS: Recombinant proteins were produced using the baculovirus/insect cell system, and wild type and three truncated cMyBP-Cs were purified using metal affinity chromatography. The interaction between recombinant proteins was analyzed in real time using biosensor technology on immobilized anti-beta-MyHC antibodies. RESULTS: Biomolecular interaction with beta-MyHC was detected for both wild type cMyBP-C and a truncated mutant lacking half of the C-terminal C10 domain. In contrast, no interaction with beta-MyHC was found for two truncated cMyBP-Cs lacking at least the C5-C9 region. CONCLUSIONS: Biosensor technology allows in vitro analysis of the interaction between human beta-MyHC and cMyBP-C mutants resulting from FHC mutations. The data show that the interaction depends on the size of the truncation. This suggests that, in the context of FHC, impairment of suitable interaction between beta-MyHC and some of the truncated cMyBP-Cs may promote degradation of the truncated proteins and therefore contribute to the development of the disease.

Animals↗

[Depression and apathy in Alzheimer's disease].

DEPRESSION IN THE ELDERLY SUBJECT: Depression is diagnosed to a varying extent in the elderly. In subjects with Alzheimer's disease, the most specific signs involve mood disorders, loss of energy, a feeling of hopelessness, and sometimes body discomfort or pain. DEFINITION OF APATHY: Apathy is defined as a loss of motivation, expressed by a loss of interest in activities, lack of productivity, loss of will and initiative, as well as limited affective response to positive or negative elements. TWO DIFFERENT SYNDROMES: The differential diagnosis is difficult, but studies have demonstrated that depression and apathy are two relatively different syndromes, which may be intertwined. Lack of volition and initiative are suggestive of apathy. Neuropsychology, particularly the capacity to divide attention, may be useful. FUNCTIONAL CONSEQUENCES: Apathy and depression both have functional effects which may accelerate institutionalization (altered capacity for initiative, adaptation to the environment). FUNCTIONAL ANATOMY AND NEUROCHEMICAL CONSEQUENCES: Apathy and to a lesser degree depression, involve prefrontal cortical areas. Involvement of the prefrontal pathways is a common feature of apathy and depression, but the other pathways are affected specifically. Cholinesterase inhibitors and selective serotonine reuptake inhibitors as well as serotoninergic antidepressants have been found to be effective for certain components of apathy.

Aged↗

How does the Hospital and Anxiety and Depression Scale measure anxiety and depression in healthy subjects?

Many anxiety and depression scales are commonly used, although the assumption that they all measure the same construct may be questioned. Thus, researchers have to pay attention to the nature of the scales they use. The Hospital Anxiety and Depression Scale (HADS) was constructed in 1983 to allow a rapid and separate measure of depression and generalised anxiety. Surprisingly, since its introduction, there has been no comprehensive documentation of its psychometric properties. Therefore, as a contribution to assessing the construct validity of the HADS, we conducted a set of confirmatory factor analyses in a sample of 195 healthy students. None of the formerly proposed models fit our data. We were able to split the original Anxiety subscale into two components that we have labelled 'Anxiety' and 'Restlessness', while the original Depression subscale is slightly modified. The results are discussed from both clinical and theoretical points of view.

Adult↗

Improved MR coronary angiography with use of a new rapid clearance blood pool contrast agent in pigs.

PURPOSE: To evaluate in an animal model the potential for clinical use of a new rapid clearance blood pool contrast agent to improve free-breathing and breath-hold magnetic resonance (MR) coronary angiography. MATERIALS AND METHODS: Free-breathing and breath-hold MR coronary angiography were performed in a pig model (n = 9) (a) without use of a contrast agent; (b) with P792 (Guerbet Research, Aulnay Sous Bois, France), a monodisperse monogadolinated macromolecular compound that acts as a blood pool contrast agent with rapid clearance properties; and (c) with an extravascular gadolinium-based contrast agent. This resulted in six imaging options, which were compared in terms of contrast-to-noise ratio (CNR), signal-to-noise ratio, and vessel length measurements by using the Student t test. RESULTS: Use of P792 improved CNR and visible vessel length significantly with both MR respiratory motion correction approaches, as compared with nonenhanced MR imaging (P <.05). CNR was improved by 76% (from 5.0 to 8.6) with the free-breathing approach and by 34% (from 6.2 to 8.2) with the breath-hold approach. Visible vessel length was increased by 27% (from 79.7 to 99.2 mm) with the free-breathing approach and by 90% (from 48.2 to 86.5 mm) with the breath-hold approach. The P792-enhanced free-breathing approach allowed more distal visualization of the coronary arteries than did the P792-enhanced breath-hold approach (P <.05). Use of the extravascular contrast agent did not improve image quality significantly when compared with that of nonenhanced MR images. CONCLUSION: Use of P792 improves coronary artery MR imaging in conjunction with free-breathing and breath-hold approaches.

Animals↗

The Spielberger Trait Anxiety Inventory measures more than anxiety.

OBJECTIVE: Researchers tried to explain the overlap between anxiety and depression by suggesting that some items of self-administered questionnaires were badly selected and that both constructs should rather be considered as multidimensional. Thus, we hypothesise that the Spielberger trait anxiety inventory (TAI) includes items related to depression. METHOD: A non-clinical sample of 193 subjects filled out the TAI and the Hospitalised Anxiety-Depression Scale. Factors were postulated on the basis of item content and submitted to confirmatory factor analysis (CFA). RESULTS: We found five factors: a 10-item anxiety factor containing three factors, a four-item unsuccessfulness factor correlated with the HADS anhedonia factor, and a six-item happiness factor. CONCLUSION: The TAI scale encompasses measures of anxiety, depression and well-being. Consequently, the overlap with other measures of depression may result from item selection. This work awaits replication in independent normal and pathological samples.

Adult↗

Impaired strategic regulation of contents of conscious awareness in schizophrenia.

Conscious awareness comprises two distinct states, autonoetic and noetic awareness. Schizophrenia impairs autonoetic, but not noetic, awareness. We investigated the strategic regulation of relevant and irrelevant contents of conscious awareness in schizophrenia using a directed forgetting paradigm. Twenty-one patients with schizophrenia and 21 normal controls were presented with words and told to learn some of them and forget others. In a subsequent test, they were asked to recognize all the words they had seen previously and give remember, know or guess responses according to whether they recognized words on the basis of autonoetic awareness, noetic awareness, or guessing. Overall, patients showed the same degree of a directed forgetting effect as normal subjects. However, whereas the effect was observed both for remember and know responses in normal subjects, it was observed for know, but not for remember, responses in patients. These results indicate that patients with schizophrenia exhibit an impaired strategic regulation of contents of autonetic awareness for relevant and irrelevant information.

Adult↗

Ambulatory system for human motion analysis using a kinematic sensor: monitoring of daily physical activity in the elderly.

A new method of physical activity monitoring is presented, which is able to detect body postures (sitting, standing, and lying) and periods of walking in elderly persons using only one kinematic sensor attached to the chest. The wavelet transform, in conjunction with a simple kinematics model, was used to detect different postural transitions (PTs) and walking periods during daily physical activity. To evaluate the system, three studies were performed. The method was first tested on 11 community-dwelling elderly subjects in a gait laboratory where an optical motion system (Vicon) was used as a reference system. In the second study, the system was tested for classifying PTs (i.e., lying-to-sitting, sitting-to-lying, and turning the body in bed) in 24 hospitalized elderly persons. Finally, in a third study monitoring was performed on nine elderly persons for 45-60 min during their daily physical activity. Moreover, the possibility-to-perform long-term monitoring over 12 h has been shown. The first study revealed a close concordance between the ambulatory and reference systems. Overall, subjects performed 349 PTs during this study. Compared with the reference system, the ambulatory system had an overall sensitivity of 99% for detection of the different PTs. Sensitivities and specificities were 93% and 82% in sit-to-stand, and 82% and 94% in stand-to-sit, respectively. In both first and second studies, the ambulatory system also showed a very high accuracy (> 99%) in identifying the 62 transfers or rolling out of bed, as well as 144 different posture changes to the back, ventral, right and left sides. Relatively high sensitivity (> 90%) was obtained for the classification of usual physical activities in the third study in comparison with visual observation. Sensitivities and specificities were, respectively, 90.2% and 93.4% in sitting, 92.2% and 92.1% in "standing + walking," and, finally, 98.4% and 99.7% in lying. Overall detection errors (as percent of range) were 3.9% for "standing + walking," 4.1% for sitting, and 0.3% for lying. Finally, overall symmetric mean average errors were 12% for "standing + walking," 8.2% for sitting, and 1.3% for lying.

Acceleration↗

Comparison of different types of blood pool agents (P792, MS325, USPIO) in a rabbit MR angiography-like protocol.

RATIONALE AND OBJECTIVES: The objective of this study is to determine the influence of the pharmacokinetic behaviors of different classes of blood pool agents (BPA) on a rabbit experimental model that mimics a magnetic resonance angiographic protocol. BPA were as follows: P792, a macromolecular agent (RCBPA), USPIO, an ultrasmall superparamagnetic iron oxide particle agent (SCBPA), and MS-325, a small gadolinium chelate that expresses intravascular behavior by reversible albumin binding. METHODS: The 2 main phases of early distribution following contrast agent injection, that is, the bolus phase and the steady-state phase, are investigated by measuring Gd or Fe blood concentrations in the first 5 minutes postinjection. T1 relaxation times and r1 relaxivity were calculated at each time point of blood sampling. Furthermore, in the case of MS-325, the concentrations of the free and bound forms were calculated, according to the measured concentrations and the apparent r1 relaxivities. RESULTS: Injected under similar conditions, the 3 BPA have, during the bolus phase, a comparable profile to Gd-DOTA. Signal enhancement was maximum during this short bolus phase, as were the T1 relaxation times under 30 ms for all agents. At 1 minute postinjection, P792 (r1 = 39 seconds(-1) x mmol/L(-1), 20 MHz) demonstrated the same pharmacokinetic behavior as USPIO (r1 = 33 seconds(-1) x mmol/L(-1), 20 MHz): C1 minute/C0 values were 91 +/- 6% and 92 +/- 12%, respectively. Immediately after the injection at clinical dose, 74% of MS-325 was in free form, resulting in an apparent r1 relaxivity of only 13 seconds(-1) x mmol/L(-1) (20 MHz); 1 minute postinjection, the C1 minute/C0 value of 61 +/- 4% was the lowest as compared with P792 and USPIO and the bound form represented 75% of the MS-325 molecules. CONCLUSIONS: The BPA P792 and USPIO have favorable properties that result from their intravascular retention and their lack of extravasation, allowing optimal contrast between the vessel and the adjacent tissue for several minutes postinjection. Combining a rapid body clearance and a marked T1 effect, P792 presents optimal blood pool characteristics for angiographic applications. During the bolus phase, MS-325 is mainly in free form, which presents the disadvantage of increasing the tissue signal background, due to extravasation of the free form.

Animals↗

Human p63RhoGEF, a novel RhoA-specific guanine nucleotide exchange factor, is localized in cardiac sarcomere.

The Rho small GTPases are crucial proteins involved in regulation of signal transduction cascades from extracellular stimuli to cell nucleus and cytoskeleton. It has been reported that these GTPases are directly associated with cardiovascular disorders. In this context, we have searched for novel modulators of Rho GTPases, and here we describe p63RhoGEF a new Db1-like guanine nucleotide exchange factor (GEF). P63RhoGEF encodes a 63 kDa protein containing a Db1 homology domain in tandem with a pleckstrin homology domain and is most closely related to the second Rho GEF domain of Trio. Northern blot and in situ analysis have shown that p63RhoGEF is mainly expressed in heart and brain. In vitro guanine nucleotide exchange assays have shown that p63RhoGEF specifically acts on RhoA. Accordingly, p63RhoGEF expression induces RhoA-dependent stress fiber formation in fibroblasts and in H9C2 cardiac myoblasts. Moreover, we show that p63RhoGEF activation of RhoA in intact cells is dependent on the presence of the PH domain. Using a specific anti-p63RhoGEF antibody, we have detected the p63RhoGEF protein by immunocytochemistry in human heart and brain tissue sections. Confocal microscopy shows that p63RhoGEF is located in the sarcomeric I-band mainly constituted of cardiac sarcomeric actin. Together, these results show that p63RhoGEF is a RhoA-specific GEF that may play a key role in actin cytoskeleton reorganization in different tissues, especially in heart cellular morphology.

Amino Acid Sequence↗

Standardized MR protocol for the evaluation of MRA sequences and/or contrast agents effects in high-degree arterial stenosis analysis.

PURPOSE: To investigate the relative role of high resolution (spatial or temporal) magnetic resonance angiography (MRA) sequence and of contrast agent properties in the evaluation of high-degree arterial stenosis. METHODS: We qualitatively and quantitatively studied both 50 and 95% (300 microm diameter) stenosis of a 6 mm arterial phantom with two contrast agents (CA), Gd-DOTA (r(1)=2.9 mM(-1) s(-1)) versus P760 (r(1)=25 mM(-1) s(-1)) at several CA concentrations, including arterial peak concentration after injection of either a single or double dose of CA, using either a high temporal (booster) or high spatial (HR) resolution 3D MRA sequences. Experimental data were then compared to theoretical data. RESULTS: With the 3D HR sequence, both visual and quantitative analysis were significantly better compared to the 3D booster sequence, at each phantom diameter. Quantitative analysis was significantly improved by injection of a double versus a single dose of each CA (Gd-DOTA or P760), primarily in high degree stenosis. CONCLUSION: Combined MRA spatial resolution and high CA efficiency are mandatory to correctly evaluate high degree stenosis.

Arterial Occlusive Diseases↗