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Biomedical subjects

M Lacour

Publications and source records attributed to M Lacour.

At least 19 recordsLinked to original sources

Changes in rat soleus muscle phenotype consecutive to a growth in hypergravity followed by normogravity.

It has been demonstrated that a long-term stay in hypergravity (HG: 2G) modified the phenotype and the contractile properties of rat soleus muscle. The ability of this muscle to contract was drastically reduced, which is a sign of anticipated aging. Consequently, our aim was to determine whether rats conceived, born, and reared in hypergravity showed adaptative capacities in normogravity (NG: 1G). This study was performed on rats divided into two series: the first was reared in HG until 100 days and was submitted to normogravity until 115 to 220 postnatal days (HG-NG rats); the second was made up of age paired groups reared in normogravity (NG rats). The contractile, morphological, and phenotypical properties of soleus muscle were studied. Our results showed that the NG rats were characterized by coexpressions of slow and fast myosin, respectively, 76.5 and 23.5% at 115 days. During their postnatal maturation, the fast isoform was gradually replaced by slow myosin. At 220 days, the relative proportions were respectively 91.05% and 8.95%. From 115 to 220 days, the HG-NG rats expressed 100% of slow myosin isoform and they presented a slower contractile behavior compared with their age-matched groups; at 115 days, the whole muscle contraction time was increased by 35%, and by 15%, at 220 days. Our study underlined the importance of gravity in the muscular development and suggested the existence of critical periods in muscle phenotype installation.

Animals↗

Kinematics of treadmill locomotion in rats conceived, born, and reared in a hypergravity field (2 g). Adaptation to 1 g.

The kinematics of treadmill locomotion in rats conceived, born, and raised in a hypergravity environment (HG: 2g) until the age of 3 months was investigated for 5 weeks after their exposition to earth's gravity. The locomotor performance of the HG rats (N=7) was compared to that of age-matched control rats (N=8) housed at 1g for the same period. Kinematic analysis of treadmill locomotion was performed up to 35 days of terrestrial life by an optoelectronic motion analyzer (ELITE system). Results showed that the HG rats exhibited a faster locomotor rhythm (increased number of steps/s), walked closer to the ground, and had a more dorsiflexed foot position. Also, HG rats had shorter steps. The data also highlight a fast adaptation to normal gravity since all the locomotor parameters returned to normal values within 3 weeks. The locomotor modifications may be seen as the persistence of a hypergravity-induced posturo-locomotor adaptation in the centrifuge and/or to more functional changes of sensorimotor systems. Because locomotor performance of HG rats is not severely affected, it is concluded that early development of locomotion processes is highly resistant to gravito-inertial changes.

Adaptation, Physiological↗

Influence of mistletoe ( Viscum album) extracts on phagocytosis/burst activity of human phagocytes.

The aim of the present study was to examine the in vitro effects of various mistletoe extracts on human phagocytes. Phagocytosis, oxidative burst, and intracellular killing were analyzed by flow cytometry. None of the mistletoe preparations investigated exhibited significant phagocytosis-enhancing properties. Different mistletoe lectin concentrations ranging from 0.025 to 20 ng/ml showed only marginal influence on phagocyte activity. Contrary to the opinion of numerous practitioners of complementary medicine, the mistletoe preparations tested do not enhance phagocytic function.

Candida albicans↗

Behavioural changes induced by early and long-term gravito-inertial force modification in the rat.

The study concerns rats conceived, born and raised in a hypergravity environment (HG: 2 g) for 3 months using a centrifuge. They were then exposed to terrestrial gravity (1 g) and submitted to behavioural tests investigating their spontaneous locomotor activity (open-field), their posture (support surface), and their vestibular function (air-righting reflex). Performances were compared to age-matched control rats housed at 1 g for the same time period. Results showed static and dynamic behavioural deficits as early as the rats were exposed to normal gravity. They exhibited strongly increased motor activity in open-field, with longer travelled distances and more scattered trajectories; in addition, the HG rats displayed more numerous rearings than controls did. They showed postural changes characterized by an enlarged support surface and they did not succeed in the air-righting reflex, due to increased time-delay for head righting. None of these changes were permanent. Indeed, for all tests, the HG rats tested after 3 weeks spent in normal terrestrial gravity exhibited behaviours similar to those of the controls. HG-induced changes in the functional properties of the vestibular system may explain the deficits showed by the HG rats once exposed to normal gravity. The adaptation process to 1 g leading to the appearance of normal behaviour takes about 3 weeks. It likely implicates a central re-evaluation of the sensory inputs and an updating of the motor commands.

Adaptation, Physiological↗

Raised limb bands developing in infancy.

Congenital cutaneous constriction bands are rare and often occur with other abnormalities, including the presence of rudimentary digits. This diverse syndrome lacks a precise definition and a satisfactory explanation. We describe two unusual cases with features previously undescribed, in which predominantly raised, annular limb bands became apparent postnatally. One infant was also born with foreshortened digits and a constricting limb band, suggesting a shared aetiology with other congenital cases. The development of raised bands during infancy would be difficult to reconcile with the widely held 'amniotic band hypothesis', and would be more in keeping with a multifocal developmental abnormality in limb growth.

Abnormalities, Multiple↗

Deficits and recovery of head and trunk orientation and stabilization after unilateral vestibular loss.

The aim of the study was to analyse changes in the orientation and stabilization of the head and trunk and their recovery after complete unilateral loss of vestibular information in humans. The ability of nine Ménière's patients to orient and stabilize their heads and trunks in space was investigated during a simple dynamic task of knee-bends and compared with the performance of 10 healthy subjects. Patients' performance was recorded before unilateral vestibular neurotomy (UVN) and during the time-course of recovery (1 week, 1 month, 3 months). Experiments were performed both in eyes open (EO) and eyes closed (EC) conditions to evaluate the role of visual cues in the recovery process. Head and trunk mean angular position (orientation) and mean maximal angular rotation (stabilization) in the roll plane and the yaw plane were recorded using a video motion analysis system. The results indicate that, in the acute stage after UVN (1 week), patients exhibit marked impairments in head and trunk orientation in both visual conditions. In the EC condition, head and trunk were deviated towards the operated side in the roll plane and the yaw plane. Head and trunk stabilization in space was impaired in the roll plane and associated with increased stabilization of the head on the shoulders. Interestingly, vision caused a complete inversion of the orientation pattern, with head and trunk rotations towards the intact side in the roll plane and the yaw plane. Relative to darkness, vision also reduced head and trunk oscillations. Recovery from abnormal head orientation in the light and impaired head stability in both visual conditions was achieved within 1 month and 3 months after UVN, respectively. However, head and trunk orientation in the dark and trunk stabilization in the roll plane remained uncompensated 3 months post-lesion. These results suggest that unilateral vestibular loss leads to a postural syndrome similar to that described previously for various animal species. They confirm the necessity of vestibular inputs for properly stabilizing head and trunk during self-generated displacements in healthy subjects. They also support the notion that vestibular compensation relies on visual cues whose substitution role gradually decreases after UVN.

Adaptation, Physiological↗

Contractile properties and myosin expression in rats born and reared in hypergravity.

The effects of hypergravity (HG) on soleus and plantaris muscles were studied in Long Evans rats aged 100 days, born and reared in 2-g conditions (HG group). The morphological and contractile properties and the myosin heavy chain (MHC) content were examined in whole muscles and compared with terrestrial control (Cont) age-paired rats. The growth of HG rats was slowed compared with Cont rats. A decrease in absolute muscle weight was observed. An increase in fiber cross-sectional area/muscle wet weight was demonstrated, associated with an increase in relative maximal tension. The soleus muscle changed into a slower type both in contractile parameters and in MHC content, since HG soleus contained only the MHC I isoform. The HG plantaris muscle presented a faster contractile behavior. Moreover, the diversity of hybrid fiber types expressing multiple MHC isoforms (including MHC IIB and MHC IIX isoforms) was increased in plantaris muscle after HG. Thus the HG environment appears as an important inductor of muscular plasticity both in slow and fast muscle types.

Animals↗

How changes in vestibular and visual reference frames combine to modify body orientation in space.

The aim of this study was to analyse how changes in vestibular and visual reference frames combine to modify body orientation in space, and to determine the relationship between postural, oculomotor and perceptive parameters. Changes in vestibular and visual references were investigated by comparing controls and vestibular defective patients (Ménière's patients tested before and one week after unilateral vestibular nerve section) under three visual contexts (light with and without vertical and horizontal coordinates, darkness). Unilateral vestibular loss was responsible for postural and perceptive deviations whose direction depended on the presence of visual reference frame. We suggest these changes vary according to the spatial reference frame patients are based on. Postural changes were related to perceptive modifications but not to eye cyclotorsion.

Adult↗

Gamma amino butyric acid (GABA) immunoreactivity in the vestibular nuclei of normal and unilateral vestibular neurectomized cats.

Recent neurochemical investigations of the central vestibular pathways have demonstrated that several neurotransmitters are involved in various operations required for stabilizing posture and gaze. Neurons of the vestibular nuclei (VN) receive GABAergic inhibitory afferents, and GABAergic neurons distributed throughout the vestibular complex are implicated in inhibitory vestibulo-ocular and vestibulo-spinal pathways. The aim of this study was to analyse the modifications of GABA immunoreactivity (GABA-ir) in the cat VN after unilateral vestibular neurectomy (UVN). Indeed, compensation of vestibular deficits is a good model for studying adult central nervous system (CNS) plasticity and the GABAergic system is involved in CNS plasticity. We studied GABA-ir by using a purified polyclonal antibody raised against GABA. Light microscopic preparations of thin (20 microm) sections of cat VN were used to quantify GABA-ir by an image analysing system measuring GABA-positive punctate structures and the number of GABA-positive neurons. Both the lesioned and intact sides were analysed in three populations of UVN cats killed at different times after injury (1 week, 3 weeks and 1 year). These data were compared to those collected in normal unlesioned and sham-operated cats. Results showed a spatial distribution of GABA-ir in the control cats that confirmed previous studies. GABA-ir neurons, fibres and nerve terminals were scattered in all parts of the VN. A higher concentration of GABA-positive neurons (small cells) was detected in the medial and inferior VN (MVN and IVN) and in the dorsal part of the lateral VN (LVNd). A higher level of GABA-positive punctate structures was observed in the MVN and in the prepositus hypoglossi (PH) nucleus. Lesion-induced changes were found at each survival time. One week after injury the number of GABA-positive neurons was significantly increased in the MVN, the IVN and the dorsal part of the LVN on the lesioned side and in the ventral part of the LVN on the intact side. One year later a bilateral increase in GABA-positive neurons was detected in the MVN whilst a bilateral decrease was observed in both the SVN and the ventral part of the LVN. Changes in the GABA-staining varicosities did not strictly coincide with the distribution of GABA-ir cells, suggesting that GABA-ir fibres and nerve terminals were also modified. One week and later after injury, higher GABA-staining varicosities were seen unilaterally in the ipsilateral MVN. In contrast, bilateral increases (in PH) and bilateral decreases (in SVN and the ventral part of the LVN) were recorded in the nearly (3 weeks) or fully (1 year) compensated cats. At this stage GABA-staining varicosities were significantly increased in the lesioned side of the MVN. These findings demonstrate the reorganization of the GABAergic system in the VN and its possible role in recovery process after UVN in the cat. The changes seen during the acute stage could be causally related to the VN neuron deafferentation, contributing to the static vestibular deficits. Those found in the compensated cats would be more functionally implicated in the dynamic aspects of vestibular compensation.

Adaptation, Physiological↗

Histamine and betahistine in the treatment of vertigo: elucidation of mechanisms of action.

The aim of this review is to provide clinicians with a picture of the mechanisms by which: histamine and histaminergic agonists act on the vestibular system both peripherally and centrally; and histaminergic agonists and antagonists interfere with the recovery process after peripheral vestibular lesion. We have focused on betahistine, a structural analogue of histamine with weak histamine H(1) receptor agonist and more potent H(3) receptor antagonist properties, to review the currently available data on the role of the histaminergic system in the recovery process after peripheral vestibular deficits and the effects of histamine analogues in the clinical treatment of vertigo. This review provides new insights into the basic mechanisms by which betahistine improves vestibular compensation in animal models of unilateral vestibular dysfunction, and elucidates particularly the mechanisms of action of this substance at the level of the CNS. It is proposed that betahistine may reduce peripherally the asymmetric functioning of the sensory vestibular organs in addition to increasing vestibulocochlear blood flow by antagonising local H(3) heteroreceptors. Betahistine acts centrally by enhancing histamine synthesis within tuberomammillary nuclei of the posterior hypothalamus and histamine release within vestibular nuclei through antagonism of H(3) autoreceptors. This mechanism, together with less specific effects of betahistine on alertness regulation through cerebral H(1) receptors, should promote and facilitate central vestibular compensation. Elucidation of the mechanisms of action of betahistine is of particular interest for the treatment of vestibular and cochlear disorders and vertigo.

Animals↗

Fos expression in the rat brain after exposure to gravito-inertial force changes.

The immediate-early genes constitute useful neurobiological tools for mapping brain functional activity after sensory stimulation. We immunohistochemically investigated Fos protein expression in the brain of rats exposed to gravito-inertial force changes. Experiments were performed in hypergravity rats born and housed for 60 days in terrestrian gravity (1xg) and thereafter exposed for 90 min to 2xg or 4xg in a centrifuge, and in hypogravity rats born and housed for 60 days at 2xg and submitted for 90 min to 1xg. Data from these two experimental groups were quantified by light microscopy and compared to those from two groups of control rats born and permanently housed in either 1xg or 2xg environments that never had to adapt to novel gravito-inertial environments. Results showed a low basal Fos expression in the controls and a strong Fos staining in the experimental rats. Only the hypergravity rats displayed Fos-positive cells in vestibular-related brainstem regions (medial, inferior, and superior vestibular nuclei (VN); group y; dorsomedial cell column (DMCC) of the inferior olive (IO)). By contrast, many suprabulbar areas were strongly labeled in both the hyper- and hypogravity rats, as shown by the numerous Fos-positive cells in mesencephalic (colliculus, laterodorsal periaqueductal gray, autonomic nuclei), diencephalic (hypothalamic and thalamic nuclei), and telencephalic (parietal, temporal, entorhinal and visual cortices) structures. These spatial patterns of Fos expression suggest that an increase in gravito-inertial force activates otolith-vestibulo-olivar pathways and various suprabulbar structures underlying the corticovestibular interactions, which govern the multiple representations of vestibular information in the cortex. A decrease in gravito-inertial force has the opposite effects on the vestibulo-olivar structures as a result of otolith system disfacilitation which, in turn, modifies the activity of complex neural pathways. Exposure to both hyper- and hypogravity environments likely induces neurovegetative and/or stress effects that could account for Fos labeling in autonomic nuclei and in nervous structures involved in the hypothalamo-pituitary-adrenal axis.

Animals↗

Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy.

Cyclosporin (CyA) has been shown to be highly effective and well tolerated in the short-term treatment of severe childhood atopic dermatitis; however, there is limited experience in its longer-term use. The aim of this study was to compare multiple short courses of CyA with continuous therapy for 1 year, with respect to efficacy, safety, tolerability and quality of life. Children aged 2-16 years, with a diagnosis of severe atopic dermatitis refractory to topical steroid therapy, were randomly assigned to receive short course therapy (multiple courses of 12 weeks) or continuous therapy. The starting dose and maximum dose for all patients was 5 mg/kg per day. Disease activity was monitored using the Six Area Six Sign Atopic Dermatitis score and the 'Rule of Nines' area score. Pruritus, sleep disturbance and irritability were measured using visual analogue scales, and topical therapy was monitored. Safety measurements included monitoring of serum creatinine, blood pressure and adverse events. Forty patients were included in the efficacy analysis, 21 of whom were randomized to the short course group (of whom six were withdrawn) and 19 to the continuous group (of whom five were withdrawn). Significant improvements were seen in all efficacy parameters at every time-point. There were no significant differences between groups, although the improvement was more consistent in the continuous arm. In the short course arm, 7 out of 21 patients could be managed by at least two short courses. The remaining 14 patients includes 12 who could not be controlled by at least two short courses, one patient who failed to return after week 12 and another patient who was withdrawn at week 4 due to an adverse event. Quality of life improved for both the children and their families. Tolerability was considered good or very good in at least 80% of the patients at week 12 and at the end of the study. No clinically significant change was seen in mean serum creatinine and no change was seen in mean blood pressure in either group. CyA is effective in controlling severe atopic dermatitis in children over a 1-year period and is well tolerated. More consistent control is achieved with continuous treatment; however, short course therapy was adequate for some patients, indicating that treatment should be tailored to the individual patient's needs. Short course treatment may produce prolonged remission in some cases and reduce the cumulative exposure to the drug.

Adolescent↗

Repeated prevalence investigations on nosocomial infections for continuous surveillance.

In order to obtain an overview for the planning of further infection control activities, nine repeated prevalence studies were performed at monthly intervals. These occurred in the surgical units of eight medium-sized German hospitals. A total of 4984 surgical patients were investigated, the number of patients observed in each hospital varied from 365 to 913 patients, an average of 69.2 patients per prevalence study per hospital. A total of 212 nosocomial infections were found, the majority being surgical site (43.9%) and urinary tract infection (33.0%). The overall prevalence rate was 4.0%. More than four repeated investigations had only a minor influence on the 95% confidence intervals, and a follow-up of late microbiological reports increased the prevalence rate by only 7.5%. However, it was very useful to record the presence of urinary catheters on the prevalence day and also the preceding days; for instance, a device-associated prevalence of 7.8 urinary tract infections per 100 patients with urinary catheters was found on the day of investigation. In order to evaluate the situation in one's own surgical department by prevalence studies and for reasons of cost-effectiveness, the workload can be limited to four repeated studies in most hospitals. A further follow-up of later microbiological reports is not recommended, and it seems useful to concentrate on patients with indwelling devices.

Cross Infection↗

Can quality circles improve hospital-acquired infection control?

It is a fundamental principle of continuous quality improvement (CQI) that processes should be the objects of quality improvement. The objective of this study was to improve process quality concerning the prevention of hospital-acquired infections in surgical departments and intensive care units by a continuous quality improvement (CQI) approach based mainly on quality circles. This approach was evaluated in a prospective controlled intervention study in medium-size acute care hospitals (four intervention and four control hospitals). During two intervention periods (each 10 months) four external physicians with training in hospital epidemiology and infection control introduced and supervised quality circles in the intervention hospitals. Process quality was assessed by interviewing senior staff members before the first and after the second intervention period using standardized questionnaires. The gold standard process quality was defined on the basis of the CDC/HICPAC-guidelines for the prevention of hospital-acquired infections. Most of the evaluated aspects of process quality belonged to the HICPAC-categories IA and IB respectively, the CDC category I. Fifty quality circle sessions were performed in the four intervention hospitals of which 28 were dealing directly with key subjects in infection control. In the intervention hospitals, 19.8% of evaluated aspects of process quality which concerned the prevention of hospital-acquired infections were improved compared to only 6.9% in the control hospitals (P<0.05). Sixty-six point seven percent of positive changes in process quality were initiated by the results of the quality circles. Our study demonstrates that a CQI approach based on infection control quality circles can lead to a substantial improvement of process quality regarding the prevention of hospital-acquired infections.

Cross Infection↗

Vestibular compensation in the cat: the role of the histaminergic system.

Histamine is thought to be involved in the recovery of vestibular function as histaminergic medications are effective in vestibular-related syndromes. We conducted studies in the cat to assess the effects of betahistine (a histamine-like substance) on the behavioural recovery process after unilateral vestibular neurectomy (UVN). We also investigated histamine immunoreactivity changes in the vestibular and tuberomammillary nuclei of betahistine-treated lesioned cats compared with untreated and unlesioned cats. Betahistine strongly accelerated the behavioural recovery process after UVN, with a time benefit of approximately 2 weeks for both static posture (support surface) and dynamic equilibrium function (locomotor balance) compared with untreated animals. A bilateral decrease in histamine immunoreactivity was seen in both acute and compensated UVN cats; this effect was strongly accentuated with betahistine treatment. In conclusion, the results indicate that vestibular lesion reduces histamine staining due to an increase in histamine release in the vestibular and tuberomammillary nuclei that promote vestibular recovery. Betahistine dihydrochloride should contribute to this process by acting on both the presynaptic histamine H3 and postsynaptic histamine H1 receptors.

Adaptation, Physiological↗

Fos expression in the cat brainstem after unilateral vestibular neurectomy.

Immediate early genes are generally expressed in response to sensory stimulation or deprivation and can be used for mapping brain functional activity and studying the molecular events underlying CNS plasticity. We immunohistochemically investigated Fos protein induction in the cat brainstem after unilateral vestibular neurectomy (UVN), with special reference to the vestibular nuclei (VN) and related structures. Fos-like immunoreactivity was analyzed at 2, 8, and 24 h, and 1 and 3 weeks after UVN. Data from these subgroups of cats were quantified in light microscopy and compared to those recorded in control and sham-operated animals submitted to anesthesia and anesthesia plus surgery, respectively. Results showed a very low level of Fos expression in the control and sham conditions. By contrast, Fos was consistently induced in the UVN cats. Asymmetrical labeling was found in the medial, inferior, and superior VN (ipsilateral predominance) and in the prepositus hypoglossi (PH) nuclei and the beta subnuclei of the inferior olive (betaIO) (contralateral predominance). Symmetrical staining was observed in the autonomic, tegmentum pontine, pontine gray, locus coeruleus and other reticular-related nuclei. As a rule, Fos expression peaked early (2 h) and declined progressively. However, some brainstem structures including the ipsilateral inferior VN and the bilateral pontine gray nuclei displayed a second peak of Fos expression (24 h-1 week). By comparing these data to the behavioral recovery process, we conclude that the early Fos expression likely reflects the activation of neural pathways in response to UVN whereas the delayed Fos expression might underlie long-term plastic changes involved in the recovery process.

Animals↗

Spatial performance of unilateral vestibular defective patients in nonvisual versus visual navigation.

The purpose of this study was to investigate the effects of unilateral vestibular neurotomy on humans ability to perform navigation tasks. These tasks provided self-motion feedback by way of either locomotor activity only (nonvisual navigation or "locomotor task") or visual motion cues only (visually simulated navigation or "visual task"). After exploration of an environment in which 4 locations were marked by different objects, subjects attempted to navigate to those locations either by reproducing the same paths as those followed during exploration, by reversing routes, or by making spatial inferences (shortcuts). Vestibular defective patients were tested one day before surgical treatment and during the recovery time course following unilateral vestibular nerve lesion (1 week, 1 month, and 3 month later). Their performance was assessed by measuring turn error and distance error in both navigation tasks and was compared to that of control subjects tested 4 times at similar time intervals. Turn error in the reproduction of previously explored routes in the locomotor task was lower in patients before surgery than in controls, suggesting the existence of compensatory processes. In the acute stage (1 week) after unilateral vestibular lesion, turn error was greater in patients than in controls for the highest level of mental representation (spatial inferences or reversing routes); impairment at making accurate rotations had disappeared by 1 month after vestibular lesion in both navigation tasks. These results point to the role of vestibular cues, in interaction with other sensory modalities, in the elaboration of an accurate internal representation of the environment. In addition, they suggest that unilateral suppression of vestibular information would induce transitory spatial memory disorganization at a high level of information processing.

Distance Perception↗