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Biomedical subjects

G Cheron

Publications and source records attributed to G Cheron.

At least 37 records · Page 2Linked to original sources

Intussusception in infants and children: feasibility of ambulatory management.

To evaluate the ambulatory management of ileo-colic intussusception in infants and children, a retrospective study over 3 years of 113 children treated for ileo-colic intussusception in a paediatric emergency department was undertaken with the aim of shortening the length of stay. A total of 113 children aged 10 days to 9 years (median 12 months) were treated for intussusception between January 1993 and December 1996. None had septic shock or peritoneal aeric effusion. Barium enema reduction was attempted in all patients. Successful reduction rate was 81%. Fifty patients (44.2%) were completely ambulatory managed and 42 were hospital-supervised after successful enema reduction. Twenty-one children underwent laparotomy after failure of enema. With the ambulatory device, costs were reduced ($1000/case) compared with conventional in-patient treatment. Outpatient treatment of acute ileo-colic intussusception is secure and reduces costs. It depends on the willingness of the medical team but requires simultaneous adaptation of hospital funding to promote this trend.

Ambulatory Care↗

Adaptive motor strategy for squatting in spastic diplegia.

Motor strategies, defined by kinetic, kinematic and/or muscle activation patterns, reflect neural planning of movement, which takes into account central as well as peripheral constraints. Major alteration is expected in cerebral palsy, a condition characterized by abnormal posture and movement secondary to early lesion of the brain. The objective of this study was to characterize the motor strategies involved in disruption of posture in cerebral palsy of the spastic diplegia type and compare them with normal controls. The optoelectronic ELITE system was used to record and analyse the movement of squatting from the standing position with the arms extended forward in 11 children with spastic diplegia aged between 3 and 12 years and 11 age-matched normal controls. Normal children maintained gaze and arm horizontality and trunk verticality throughout the movement. The knee followed an oblique trajectory. Its angular velocity profile showed a short, single-peaked, ascending phase. The onset of movement was preceded by deactivation of the semimembranous muscle. In diplegic children, gaze and arm horizontality and trunk verticality were lost. The ankle was rigidified, resulting in spatial fixation of the knee. The ascending phase of the knee velocity profile was prolonged and multi-peaked. There was widespread muscle co-contraction from the outset of movement. No anticipatory deactivation was evidenced, but anticipatory bursts appeared in the soleus. Patients with cerebral palsy have to organize a limited motor repertoire from a restricted neural potential. Consequent motor strategies presently demonstrated in spastic diplegia are distinct and appear as an original alternative to those of normal subjects.

Biomechanical Phenomena↗

Kinematics invariance in multi-directional complex movements in free space: effect of changing initial direction.

We investigated in normal human subjects the effect of changing the initial direction on the kinematic properties of figure '8' movement performed as fast as possible by the right arm extended in free space. To this end, the motion of the index finger was monitored by the ELITE system. The figure '8' movement was characterized by a complex tangential velocity profile (Vt) presenting 5 bell-shaped components. It was found that the temporal segmentation following Vt was not significantly different, whatever the initial direction of the movement. The decomposition of Vt into different velocity profiles with respect to vertical (3 phases, Iy-IIIy) and horizontal (5 phases, Iz-Vz) directions showed a significant relationship between the amplitude and the maximal velocity for all the different phases (except the IIy phase), which demonstrated a good conservation of the Isochrony Principle. However, we showed that the transition between the clockwise and counter-clockwise loop (inflection point) induced greater variability in the vertical velocity profile than in the horizontal one. Moreover, some parameters such as the maximal velocity of Iy and the movement amplitude of the last phases (IIIy and Vz) showed significant changes depending on the initial direction. A highly significant positive correlation was observed between the instantaneous curvature and angular velocity. This was expressed by a power law similar to that previously describe for other types of movement. Furthermore, it was found that this covariation between geometrical and kinematic properties of the trajectory is not dependent on the initial direction of movement. In conclusion, these results support the idea that the fast execution in different directions of a figure '8' movement is mainly controlled by two types of invariant commands. The first one is reflected in the 2/3 power law between angular velocity and curvature and the second one is represented by a segmented tangential velocity profile.

Adult↗

Transcriptional activation of CYP2C, MxA and Fas in sudden infant death syndrome.

The expression of cytochrome P4502C has been shown to be upregulated in sudden infant death syndrome (SIDS) and could be linked to viral infection through the release of interferon alpha and interleukins. MxA is a reliable marker of IFNalpha release and its level was significantly enhanced in SIDS reflecting the release of IFNalpha in response to viral infection. Similarly, the concentration of Fas protein was increased in SIDS (2.6x control) and indicated a stimulation of the Fas gene expression. Accumulation of MxA and Fas proteins were visible in liver and to a lesser extent in lung and kidney. The amount of RNA encoding CYP2C9 (4.4x control), 2C8 (2.5x) and 2C18 (2.3x) was markedly higher in SIDS than in age-matched children and would suggest a transcriptional activation of CYP2C gene expression. Finally, CYP2C genes were shown to be adjacent to two IFN-inducible genes (IFI54 and IFI56) on chromosome 10. We conclude that in SIDS a viral infection leads to the release of IFNalpha which could activate a battery of IFN-inducible genes. This might modify the chromatin structure and facilitate the accessibility to promoter/regulatory sequences of CYP2C and Fas genes close to IFN-inducible gene on chromosome 10.

Adaptor Proteins, Signal Transducing↗

Multi-joint coordination strategies for straightening up movement in humans.

Complex movement execution theoretically involves numerous biomechanical degrees of freedom, leading to the concept of redundancy. The kinematics and kinetics of rapid straightening up movement from the squatting position were analysed with the optoelectronic ELITE system in 14 subjects. We found multiple acceleration and deceleration peaks for the hip, knee and ankle joints during the early extension phase of the movement. In order to test the temporal coordination between the angular acceleration of these joints, conjugate crosscorrelation functions (CCF) between each set of two variables were calculated. We found a bimodal distribution of the maximum CCF in positive and negative values suggesting the existence of two distinct strategies, the in-phase and the out-of-phase strategy for each pair of joints. The hip and knee coordination strategies (in- or out-of-phase) were well conserved in each subject for repetitive movements. Combination of joint pair strategies was more reproducible for the hip-knee/knee-ankle pair than for the other combinations, suggesting that the straightening up strategies are organised around the knee. We conclude that mastering of the redundancy problem can be realised by using coordination strategies characterised by opposed joint acceleration patterns.

Acceleration↗

Hand trajectory formation during whole body reaching movements in man.

End-effector trajectory formation was studied during a reaching movement using the whole body. The movements of various parts of the body were measured with the optoelectronic ELITE system. Wrist reaching movement paths showed noticeable curvatures. The analysis of various marker onset latencies revealed that the wrist was the last to move, always after the head, knee or trunk, suggesting a subordinate role of the focal component with respect to the primary role of the equilibrium component. These results suggest that reaching wrist movements are subjected to whole-body equilibrium constraints in addition to constraints placed upon end-effector kinematics or the dynamic optimization of upper-limb movements.

Adult↗

Expression of CYP3A in the human liver--evidence that the shift between CYP3A7 and CYP3A4 occurs immediately after birth.

CYP3A isoforms are responsible for the biotransformation of a wide variety of exogenous chemicals and endogenous steroids in human tissues. Two members of the CYP3A subfamily display developmentally regulated expression in the liver; CYP3A7 is expressed in the fetal liver, whereas CYP3A4 is the major cyrochrome P-450 isoform present in the adult liver. To gain insight into the descriptive ontogenesis of CYP3A isoforms during the neonatal period, we have developed several approaches to explore a neonatal liver bank. Although CYP3A4 and CYP3A7 are structurally closely related, they differ in their capacity to carry out monooxygenase reactions. We have cloned CYP3A4 and CYP3A7 and established stable transfectants in Ad293 cells to investigate their substrate specificities. The 16alpha hydroxylation of dehydroepiandrosterone is catalyzed by both proteins, but CYP3A7 has a higher affinity and maximal velocity than CYP3A4. Conversely, the conversion of testosterone into its 6beta derivative is essentially supported by CYP3A4. We used these two probes to determine the ontogenic evolution at the protein level; CYP3A7 was very active in the fetal liver and its activity was maximal during the first week following birth before to progressively decline and reached a very low level in adult livers. Conversely, the activity of CYP3A4 was extremely weak in the fetus and began to raise after birth to reach 30-40% of the adult activity after one month. CYP3A4 RNA accumulation displays a similar pattern of evolution; when probed with an oligonucleotide, its concentration increased rapidly after birth to reach a plateau as soon as the first week of age. These data supports the assumption that CYP3A4 expression is transcriptionally activated during the first week after birth and is accompanied by a simultaneous decrease of CYP3A7 expression, in such a way that the overall CYP3A protein content and the level of pentoxyresorufin dealkylase catalyzed by the two proteins remain nearly constant.

Adult↗

Emergence of clusters in the hidden layer of a dynamic recurrent neural network.

The neural integrator of the oculomotor system is a privileged field for artificial neural network simulation. In this paper, we were interested in an improvement of the biologically plausible features of the Arnold-Robinson network. This improvement was done by fixing the sign of the connection weights in the network (in order to respect the biological Dale's Law). We also introduced a notion of distance in the network in the form of transmission delays between its units. These modifications necessitated the introduction of a general supervisor in order to train the network to act as a leaky integrator. When examining the lateral connection weights of the hidden layer, the distribution of the weights values was found to exhibit a conspicuous structure: the high-value weights were grouped in what we call clusters. Other zones are quite flat and characterized by low-value weights. Clusters are defined as particular groups of adjoining neurons which have strong and privileged connections with another neighborhood of neurons. The clusters of the trained network are reminiscent of the small clusters or patches that have been found experimentally in the nucleus prepositus hypoglossi, where the neural integrator is located. A study was conducted to determine the conditions of emergence of these clusters in our network: they include the fixation of the weight sign, the introduction of a distance, and a convergence of the information from the hidden layer to the motoneurons. We conclude that this spontaneous emergence of clusters in artificial neural networks; performing a temporal integration, is due to computational constraints, with a restricted space of solutions. Thus, information processing could induce the emergence of iterated patterns in biological neural networks.

Animals↗

Evidence of a preprogrammed deactivation of the hamstring muscles for triggering rapid changes of posture in humans.

Normal subjects were asked to make rapid flexions of the legs from a stationary initial standing posture in a self-paced mode. Because this movement implicates a rapid change in posture, questions were asked about the type of central command which must include the rupture of the erect posture and the accomplishment of the goal directed movement. Movements of the different segments of the body were recorded and analyzed using the optoelectronic ELITE system. Electromyographic (EMG) activities of 8 muscles of the lower limb on one side were recorded, rectified and integrated. The time relationships of the different EMG signals (activation or deactivation) were analyzed with respect to selected kinetic measures of the related segments of the body. In the majority of the subjects, before the movement onset, EMG events included a specific deactivation of the tonic EMG activity of the semimembranous (SM) and semitendinous (ST) muscles (time onset relative to the onset of the legs flexion: -196.9 +/- 96.4 ms and -180.5 +/- 89.7 ms, respectively). A second event was a phasic activation of the tibialis anterior (TA) muscle (time onset: -60.5 +/- 117.6 ms). Conjugate cross-correlation analysis of these EMG signals demonstrated the existence of a common coordinated strategy between the deactivation of the hamstring and the TA activation. Even though a small horizontal displacement of the head was recorded prior to leg movement, it occurred too late to induce deactivation of the hamstring muscles. These results demonstrate that for rapid legs flexion, where the gravity forces are the main source of joint angle acceleration, the deactivation of the SM and ST muscles acts in conjunction with the phasic activation of the TA. The preprogrammed deactivation of the SM and ST muscles represents the early phase of the central command to switch from the standing to the squatting posture.

Adult↗

Developmental expression of CYP2C and CYP2C-dependent activities in the human liver: in-vivo/in-vitro correlation and inducibility.

Experiments were performed in vivo and in vitro to date the onset of hepatic CYP2C isoforms and CYP2C-dependent activities during the perinatal period in humans. Proteins were not detected by immunoblotting in fetal livers and developed in the first few weeks after birth, irrespective of the gestational age at birth. Similarly, the hydroxylation of tolbutamide, a marker for CYP2C9 was undetected in fetal liver microsomes and rose in the first month after birth. In adult liver preparations, the hydroxylation of diazepam correlated well with the CYP3 A content of microsomes (r = 0.858, p < 0.01) and with the 6 beta hydroxylation of testosterone (r = 0.830, p < 0.005), whereas demethylation was related to the bulk of CYP2C proteins (r = 0.865, p < 0.005). In fetal liver microsomes, hydroxylation and demethylation activities accounted for less than 5% of the adult activities and both increased immediately after birth to reach adult activities at 1 year of age. When diazepam was given for sedative purpose in neonates and infants, the in-vivo urinary excretion of desmethyl diazepam, temazepam and oxazepam was extremely low in 1-2 day newborns (less than 5 nmol metabolites excreted in 24 h per kg body weight) and developed in the first week after birth. In newborns, barbiturates and to a lesser extent steroids, acted as inducers of CYP2C isoforms and increased tolbutamide hydroxylation, diazepam demethylation and diazepam hydroxylation by 2 to 10-fold. The surge of CYP2C proteins was caused by an accumulation of RNAs occurring in the first week after birth. The hepatic content in CYP2C8, 2C9 and 2C18 RNA displayed the same profile of evolution, which suggested a coregulation of their synthesis during the neonatal period. Taken together, these biochemical and clinical data enable dating of the onset of CYP2C proteins to the first weeks after birth, which is of considerable clinical importance in pediatric pharmacology.

Adult↗

Chest wall motion during tidal breathing.

We have used an automatic motion analyzer, the ELITE system, to study changes in chest wall configuration during resting breathing in five normal, seated subjects. Two television cameras were used to record the x-y-z displacements of 36 markers positioned circumferentially at the level of the third (S1) and fifth (S2) costal cartilage, corresponding to the lung-apposed rib cage; midway between the xyphoid process and the costal margin (S3), corresponding to the abdomen-apposed rib cage; and at the level of the umbilicus (S4). Recordings of different subsets of markers were made by submitting the subject to five successive rotations of 45-90 degrees. Each recording lasted 30 s, and three-dimensional displacements of markers were analyzed with the Matlab software. At spontaneous end expiration, sections S1-3 were elliptical but S4 was more circular. Tidal changes in chest wall dimensions were consistent among subjects. For S1-2, changes during inspiration occurred primarily in the cranial and ventral directions and averaged 3-5 mm; displacements in the lateral direction were smaller (1-2 mm). On the other hand, changes at the level of S4 occurred almost exclusively in the ventral direction. In addition, both compartments showed a ventral displacement of their dorsal aspect that was not accounted for by flexion of the spine. We conclude that, in normal subjects breathing at rest in the seated posture, displacements of the rib cage during inspiration are in the cranial, lateral outward, and ventral directions but that expansion of the abdomen is confined to the ventral direction.

Adult↗

Cytochrome P-450 expression in sudden infant death syndrome.

In the human liver, the major rise of the cytochrome P-450 isoform content occurs during the first months following birth (e.g., the high vulnerability period to sudden infant death syndrome (SIDS), a syndrome frequently associated with viral infection and drug hypersensitivity. We examined the expression of individual P-450 isoforms in liver samples collected postmortem from SIDS infants and compared values with those of control adults and children of the same age suffering from various pathologies. Hepatic microsomes were prepared and examined for their content in total P-450, the level of individual isoforms (CYP1A2, CYP2E1, CYP4A, CYP3A, and CYP2C) determined with specific antibodies and for their enzymatic activities. Total RNA was extracted and probed with several CYP cDNAs and oligomers. The overall hepatic P-450 content was not modified in SIDS infants. Among cytochrome P-450 isoforms, only CYP2C was markedly increased. This rise resulted from an accumulation of RNA encoding CYP2C and was associated with a stimulation of diazepam demethylation. The precocious expression of CYP2C in SIDS could result in a higher production of epoxyeicosatrienoic acids in the neonate, believed to act as relaxant of pulmonary smooth muscles. Its consequence might be the induction of fatal apnea in SIDS.

Base Sequence↗

The hypothesis of the uniqueness of the oculomotor neural integrator: direct experimental evidence in the cat.

1. As far as horizontal eye movements are concerned, the well-known hypothesis, not yet experimentally proved, of the common neural integrator states that the eye-position signal is generated by a common network, regardless of the type of versional movement. The aim of this study was to evaluate the validity of this hypothesis by checking whether the sensitivity to eye position of the neurones of the nucleus prepositus hypoglossi (NPH) (the main component of the system integrating the different incoming velocity signals) would be the same regardless of the type of versional movement. 2. The discharge of sixty-five NPH neurones was recorded in the alert cat during spontaneous eye movements made in the light and in response to sinusoidal rotations of the head in complete darkness. 3. For each NPH neurone, the sensitivity to eye position was determined from measurements carried out during intersaccadic fixation. The discharge rate of the studied neurone was plotted against eye position. The slope of the resulting regression line gave the sensitivity (measured during intersaccadic fixation in the light) of the neurone to eye position, which was termed K(f). 4. A new method was developed to measure the sensitivity to eye position (K(v)) of neurones during vestibular slow phases. The difficulty came from the fact that, during slow phases, eye velocity and eye position changed simultaneously and that each of those two variables could influence neuronal activity. For each neurone, the instantaneous firing rate was measured each time the eye passed through a given position during any slow phase generated during any vestibulo-ocular reflex. At a given position, the discharge rate of the neurone under study was plotted against the eye velocity. From the resulting linear regression line, two interesting values were obtained: its slope, corresponding to the sensitivity of the neurone to eye velocity, R(v), (at that given eye position) and its 'y'-intercept, F(0), the interpolated firing rate when the eye velocity was zero. This procedure was repeated for different eye positions. The values of F(0) were then plotted against the eye positions. The slope of the resulting regression line gave the sensitivity (measured during vestibular stimulation) of the neurone to eye position, which was termed K(v). 5. The errors on the individual values of K(f) and K(v) were assessed in order to allow a statistical comparison at the single unit level. 6. We found that, for each of our sixty-five neurones, the sensitivity to eye position measured during intersaccadic fixation in the light was equal to the sensitivity to eye position measured during the vestibulo-ocular reflex (VOR) elicited in complete darkness. We conclude that our results favour the hypothesis of a unique horizontal oculomotor integrator for all versional movements.

Animals↗