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Biomedical subjects

M Lacour

Publications and source records attributed to M Lacour.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

Homozygous nonsense mutation in helix 2 of K14 causes severe recessive epidermolysis bullosa simplex.

We have studied a consanguineous family containing two children with severe, generalized epidermolysis bullosa simplex (EBS). Electron microscopy of skin biopsies from the affected individuals showed that basal keratinocytes were devoid of tonofilament bundles, although some single intermediate filament were visible. Genetic linkage analysis with the microsatellite probe D12S96 excluded the type II keratin gene cluster in this family. However, homozygosity by descent was observed with the polymorphic probes KRT9, KRT10 Ava II, and D17S1787 in both affected children, consistent with a recessive defect in a type I keratin. Immunoreactivity to keratin K5 and K15 was normal, but monoclonal antibodies LL001 and RCK107 against K14 showed no staining, suggesting a deficiency of K14 in these individuals. mRNA extracted from biopsy material was amplified by RT-PCR to obtain full-length K14 cDNA. Direct automated sequencing identified a homozygous nonsense mutation, W305X. A Hinf I restriction enzyme site is created by this nucleotide transition, which was used to confirm the presence of the mutation in this kindred and exclude it from 100 normal chromosomes. This is the fourth kindred with severe recessive EBS for whom a mutation has been found in the K14 gene. In this instance, the premature termination codon is the farthest downstream of the reported cases, occurring in the helix 2 domain and so giving a much longer translation product. Nevertheless, the heterozygous carriers are unaffected by the disease and display no epidermal fragility. We postulate that translation of the potentially dominant-negative truncated K14 might be down-regulated due to instability of the mutant mRNA, as observed in previous cases with similar mutations.

Base Sequence↗
PubMed1998

Short-term changes in neck muscle and eye movement responses following unilateral vestibular neurectomy in the cat.

The purpose of this study was to investigate changes in neck muscle and eye movement responses during the early stages of vestibular compensation (first 3 weeks after unilateral vestibular neurectomy, UVN). Electromyographic (EMG) activity from antagonist neck extensor (splenius capitis) and flexor (longus capitis) muscles and eye movements were recorded during sinusoidal visual and/or otolith vertical linear stimulations in the 0.05-1 Hz frequency range (corresponding acceleration range 0.003-1.16 g) in the head-fixed alert cat. Preoperative EMG activity from the splenius and longus capitis muscles showed a pattern of alternate activation of the antagonist neck muscles in all the cats. After UVN, two motor strategies were observed. For three of the seven cats, the temporal activation of the individual neck muscles was the same as that recorded before UVN. For the other four cats, UVN resulted in a pattern of coactivation of the flexor and extensor neck muscles because of a phase change of the splenius capitis. In both subgroups, the response patterns of the antagonist neck muscles were consistent for each cat independently of the experimental conditions, throughout the 3 weeks of testing. Cats displaying alternate activation of antagonist neck muscles showed an enhanced gain of the visually induced neck responses, particularly in the high range of stimulus frequency, and a gain decrease in the otolith-induced neck responses at the lowest frequency (0.25 Hz) only. By contrast, for cats with neck muscle coactivation, the gain of the visually induced neck responses was basically unaffected relative to preoperative values, whereas otolith-induced neck responses were considerably decreased in the whole range of stimulation. As concerns oculomotor responses, results in the two subgroups of cats were similar. The optokinetic responses were not affected by the vestibular lesion. On the contrary, otolith-induced eye responses showed a gain reduction and a phase lead. Deficits and short-term changes after UVN of otolith- and semicircular canal-evoked collic and ocular responses are compared.

Animals↗
PubMed1998

Distribution of choline acetyltransferase immunoreactivity in the vestibular nuclei of normal and unilateral vestibular neurectomized cats.

Post-lesion recovery of vestibular functions is a suitable model for studying adult central nervous system plasticity. The vestibular nuclei complex (VN) plays a major role in the recovery process and neurochemical reorganizations have been described at this brainstem level. The cholinergic system should be involved because administration of cholinergic agonists and antagonists modify the recovery time course. This study was aimed at analysing the postlesion changes in choline acetyltransferase immunoreactivity (ChAT-Ir) in the VN of cats killed 1 week, 3 weeks or 1 year following unilateral vestibular neurectomy. ChAT-positive neurons and varicosities were immunohistochemically labelled and quantified (cell count and surface measurement, respectively) by means of an image analysing system. The spatial distribution of ChAT-Ir within the VN of control cats showed darkly stained neurons and varicosities mainly located in the caudal parts of the medial (MVN) and inferior (IVN) VN, the nucleus prepositus hypoglossi (PH) and, to a lesser extent, in the medial part of the superior vestibular nucleus (SVN). Lesion-induced changes consisted in a significant increase in both the number of ChAT-positive neurons (IVN, SVN) and the surface of ChAT-positive varicosities (IVN, SVN, PH). They were observed bilaterally in the acute (1 year and 3 weeks) and compensated (1 year) cats for the SVN and PH, while they persisted only in the IVN on the lesioned side in the compensated cats. These findings demonstrate vestibular lesion-induced reorganization of the cholinergic system in the IVN, SVN and PH which could contribute to postural and oculomotor function recovery.

Animals↗
PubMed1997

Histamine immunoreactivity changes in vestibular-lesioned and histaminergic-treated cats.

Histamine is likely involved in vestibular function recovery since histaminergic medications are effective in vestibular-related syndromes. We investigated the histamine immunoreactivity changes after unilateral vestibular neurectomy and the effects of betahistine (a partial histamine H1 receptor agonist and an histamine H3 receptor antagonist) and thioperamide (a pure histamine H3 receptor antagonist) treatment in cats. Histamine staining was analyzed in the tuberomammillary and vestibular nuclei through immunohistochemical methods and quantification techniques in light microscopy. Unilateral vestibular neurectomy induced a strong bilateral decrease in histamine immunoreactivity in the vestibular nuclei and a smaller reduction in the tuberomammillary nuclei in both acute (1 week) and compensated (3 weeks, 1 year) cats. One-week thioperamide or betahistine treatment led to a near-total lack of staining in these structures in both lesioned and control cats. One-month betahistine treatment had weaker effects in the compensated cats. We conclude that vestibular lesions reduce histamine staining because of an increase in histamine release in the vestibular and tuberomammillary nuclei, promoting vestibular functions recovery, and betahistine could contribute to this process by acting on both the presynaptic histamine H3 and postsynaptic histamine H1 receptors.

Animals↗
PubMed1997

Sensory strategies in human postural control before and after unilateral vestibular neurotomy.

Vestibular inputs tonically activate the anti-gravitative leg muscles during normal standing in humans, and visual information and proprioceptive inputs from the legs are very sensitive sensory loops for body sway control. This study investigated the postural control in a homogeneous population of 50 unilateral vestibular-deficient patients (Ménière's disease patients). It analyzed the postural deficits of the patients before and after surgical treatment (unilateral vestibular neurotomy) of their diseases and it focused on the visual contribution to the fine regulation of body sway. Static posturographic recordings on a stable force-plate were done with patients with eyes open (EO) and eyes closed (EC). Body sway and visual stabilization of posture were evaluated by computing sway area with and without vision and by calculating the percentage difference of sway between EC and EO conditions. Ménière's patients were examined when asymptomatic, 1 day before unilateral vestibular neurotomy, and during the time-course of recovery (1 week, 2 weeks, 1 month, 3 months, and 1 year). Data from the patients were compared with those recorded in 26 healthy, age- and sex-matched participants. Patients before neurotomy exhibited significantly greater sway area than controls with both EO (+52%) and EC (+93%). Healthy participants and Ménière's patients, however, displayed two different behaviors with EC. In both populations, 54% of the subjects significantly increased their body sway upon eye closure, whereas 46% exhibited no change or significantly swayed less without vision. This was statistically confirmed by the cluster analysis, which clearly split the controls and the patients into two well-identified subgroups, relying heavily on vision (visual strategy, V) or not (non-visual strategy, NV). The percentage difference of sway averaged +36.7%+/-10.9% and -6.2%+/-16.5% for the V and NV controls, respectively; +45.9%+/-16.8% and -4.2%+/-14.9% for the V and NV patients, respectively. These two distinct V and NV strategies seemed consistent over time in individual subjects. Body sway area was strongly increased in all patients with EO early after neurotomy (1 and 2 weeks) and regained preoperative values later on. In contrast, sway area as well as the percentage difference of sway were differently modified in the two subgroups of patients with EC during the early stage of recovery. The NV patients swayed more, whereas the V patients swayed less without vision. This surprising finding, indicating that patients switched strategies with respect to their preoperative behavior, was consistently observed in 45 out of the 50 Ménière's patients during the whole postoperative period, up to 1 year. We concluded that there is a differential weighting of visual inputs for the fine regulation of posture in both healthy participants and Ménière's patients before surgical treatment. This differential weighting was correlated neither with age or sex factors, nor with the clinical variables at our disposal in the patients. It can be accounted for by a different selection of sensory orientation references depending on the personal experience of the subjects, leading to a more or less heavy dependence on vision. The change of sensory strategy in the patients who had undergone neurotomy might reflect a reweighting of the visual and somatosensory cues controlling balance. Switching strategy by means of a new sensory selection of orientation references may be a fast adaptive response to the lesion-induced postural instability.

Adult↗
PubMed1996

[Nosocomial infections in Germany. Microbiological diagnosis, preventive antibiotics and antibiotic therapy].

BACKGROUND: The NIDEP-study (Nosocomial Infections in Germany-Prevalence and Prevention) is the first large multicenter survey to examine the prevalence of nosocomial infections (NI) in Germany. This part of the NIDEP-study describes the frequency and quality of the microbiological diagnosis, antimicrobial chemoprophylaxis and therapy in representative German hospitals. PATIENTS AND METHOD: Prevalence of nosocomial infections in 14 966 patients of 72 randomly selected representative German hospitals was determined. Frequency, nature and results of the microbiological diagnosis, antimicrobial chemoprophylaxis and therapy were recorded simultaneously. RESULTS: The total prevalence rate of nosocomial infections was 3.5%. The most common infections were urinary tract infections (42.1%), lower respiratory tract infections (20.6%), postoperative wound infections (15.8%), and septicemia (8.3%). Microbiological evaluation was done in 56.5% of the patients with infections. Only five of the 49 hospitals with less than 400 beds and only nine of the 23 hospitals with more than 400 beds had their own microbiological department. Antimicrobial chemotherapy was administered in 17.7% of the patients. In 35.1% of the patients who were treated with antibiotics, no clinical diagnosis of infection was made, criteria for nosocomial infections were not fulfilled or microbiological evaluation was not established. Antimicrobial chemoprophylaxis was done in one third of the patients. Prophylaxis was missed in 20.6% of patients with colorectal operations, 60.1% of appendectomies, 48% of vaginal hysterectomies, and 35.5% of total hip replacements. On the other hand antimicrobial chemoprophylaxis was frequently administered in clean procedures without increased risk of postoperative wound infections. CONCLUSION: Insufficient microbiological evaluation, inadequate perioperative antimicrobial chemoprophylaxis and administration of chemotherapy without documented infection were detected in representative German hospitals.

Anti-Bacterial Agents↗
PubMed1996

Distribution of histaminergic axonal fibres in the vestibular nuclei of the cat.

The histaminergic projection in the cat brain originates from neurones located in the tuberomammillary nucleus. The distribution of histaminergic axonal fibres was investigated immunohistochemically in the vestibular nuclei of the cat using an antibody to histamine. Labelled fibres were sparsely distributed in the whole vestibular nuclei complex and were typically beaded with small, darkly stained swellings. Staining density was low to moderate compared with that of other structures in the cat brain. Histaminergic fibre distribution showed spatial variations, with significantly heavier labelling in the superior and medial vestibular nuclei than in the lateral and inferior nuclei. Histamine could play a neuromodulatory role in the processing of sensory afferent information in the vestibular nuclei and in the control of vestibular functions.

Animals↗
PubMed1996

[Nosocomial infections intensive care units. A nation-wide prevalence study].

UNLABELLED: In a large, multicenter survey in 1994, the prevalence of nosocomial infections in German hospitals was examined, predominant pathogens were identified, and possible risk factors evaluated. In this paper the results from the intensive care units (ICUs) are presented. METHODS: Seventy-two representative hospitals in Germany were selected by randomisation and divided into four different groups according to their size (< 200 beds; 200-400 beds; 400-600 beds; > 600 beds). During 10 months four especially trained doctors documented the patients clinical and laboratory data and possible endogenous and exogenous risk factors for nosocomial infections. For better evaluation, they discussed the cases with the responsible senior officers and health care workers and visited the patients. Diagnosis of nosocomial infection was based on CDC criteria. RESULTS: In 515 patients in 89 ICUs, 78 hospital-acquired infections were documented (15.3%). The most common were pneumonia (5.9%), bronchitis (2.7%), urinary tract infections (2.4%), and septicaemia (2.2%). Possible exogenous risk factors included: peripheral venous catheters (65.6%); catheterisation of the urinary tract (64.5%); central venous catheters (60.4%); gastric tubes (38.0%); wound drainage (28.6%) and artificial ventilation (27.6%). The most frequent concomitant diseases were cardiovascular (61.9%), diabetes (20.2%), malignancies (18.8%), pre-existing infections (15.3%), and chronic respiratory disease (14.0%). The prevalence of nosocomial infections was higher in hospitals with more than 600 beds than in smaller ones (28.3% versus 12.9%, P < 0.001). Predominant pathogens were Pseudomonas aeruginosa, enterococci, Staphylococcus aureus, Candida spp., Escherichia coli, and Klebsiella spp.. Fifty per cent of the ICUs changed ventilation tubes and 66.3% changed infusion sets daily; 34.8% of patients received drugs for the prevention of stress ulcers that neutralise or decrease production of gastric acid; only 7.6% received sucralfate. Routine microbiological surveillance of tracheal aspirates and urine was done by 25.9% and 24.6% of the ICUs, respectively. DISCUSSION: Nosocomial infections are seen far more often in ICUs than on normal wards due to the immuno-suppressed state of many ICU patients and the continuous use of invasive diagnostic and therapeutic procedures. Most of these infections are of endogenous origin. Other prevalence surveys have shown results comparable to ours. Daily changing of ventilation tubes is no longer necessary, but is still routine in many hospitals. Infusion sets were also changed more often than required. The use of selective decontamination of the digestive tract for the prevention of pneumonia is still controversial; in our study it was practised in only 1.5% of the cases. The most commonly used drugs for the prevention of stress ulcers were H2-receptor blocking agents, although it has been shown that sucralfate is the better choice, as it can help prevent nosocomial pneumonia. Routine microbiological surveillance of tracheal aspirates and urine was done in 25.9% and 24.6% of the ICUs. No study so far has shown that routine cultures of tracheal secretions and urine have a preventive effect regarding infection.

Adult↗
PubMed1996

Role of the pulsed dye laser in the management of ulcerated capillary haemangiomas.

A complication of capillary haemangiomas is ulceration, which may arise after trauma and/or infection. Until recently, conservative management was the rule. However, the recent advent of the pulsed dye laser has revolutionised the treatment of vascular birthmarks and provided a new tool for the management of capillary haemangiomas. Thirteen cases of ulcerated capillary haemangiomas referred to our department were reviewed; five were treated conservatively and eight were treated with the laser. Those treated with the laser had all failed conservative management and healed completely within one to four weeks. Remarkably rapid alleviation of pain was achieved. For those haemangiomas around the mouth and perineum, laser treatment enabled early restoration of normal feeding, micturition, and defaecation. It is therefore recommended that if ulcerated capillary haemangiomas do not improve after a short period of optimal conservative treatment, laser treatment should be considered.

Female↗
PubMed1996

Confirmation of linkage of Sjögren-Larsson syndrome to chromosome 17 in families of different ethnic origins.

Linkage analysis in two consanguineous pedigrees of Pakistani and English origin and one further Indian family in which affected subjects have Sjögren-Larsson syndrome (SLS) showed linkage to chromosome 17. Linkage of SLS to D17S783 and D17S805 has been reported in Swedish pedigrees, but since those data were generated from a single ethnic group originating from a common ancestor, there remained the question of whether this disease is genetically heterogeneous. This report confirms the linkage in non-Swedish pedigrees and, therefore, provides evidence to support a single locus for SLS.

Chromosome Mapping↗
PubMed1996

Update on Sjögren-Larsson syndrome.

Sjögren-Larsson syndrome (SLS, MIM 270200) is a rare autosomal recessive neurocutaneous disorder due to a deficiency of the fatty aldehyde dehydrogenase and defined by a characteristic triad of symptoms including congenital ichthyosis, spastic di- or quadriplegia and mental retardation. Recently, genetic studies have subsequently shown linkage of the syndrome to chromosome 17p in Swedish pedigrees, confirmation of linkage to the same locus in non-Swedish pedigrees, and finally cloning of the gene as well as detection of mutations in affected probands. Furthermore, SLS may well be soon added to the list of peroxisomal disorders. The purpose of this paper is to provide an up-to-date synopsis of SLS and to outline specific aspects of this syndrome that are still unclear.

Aldehyde Dehydrogenase↗
PubMed1996

Cyclic adenosine monophosphate (cAMP) differentially regulates IL-4 in thymocyte subsets.

It was recently reported that cAMP upregulated IL-4 in T cell lines generated in vitro and expressing an unrestricted lymphokine pattern. In order to study the effect of cAMP on IL-4 released by freshly isolated T cell populations, we tested various T cell subsets that have previously been reported to synthesize this lymphokine. We found that cAMP upregulated IL-4 release from in vivo activated single CD4+ peripheral T cells and CD4+CD8-HSAlowNK1.1- thymocytes stimulated with ionomycin and phorbol ester. Furthermore, as in conventional single CD4+ or CD8+ thymocytes, cAMP enhanced IL-4 production in CD4+CD8-NK1.1+ thymocytes. This latter subset has recently been shown to belong to a independent T cell lineage that is positively selected by MHC class I molecules, recognizes CD1 and expresses a restricted T cell receptor repertoire. In contrast, cAMP appeared not to upregulate IL-4 in a third independent T cell lineage. This was suggested by the observation that cAMP did not increase IL-4 in CD3+CD4-CD8- thymocytes, which are thought not to give rise to conventional single CD4+ or CD8+ T cells. It therefore appears that cAMP is coupled differently to IL-4, depending on the T cell lineage. In contrast, in all IL-4 producing stages of conventional T cells, IL-4 is consistently upregulated by cAMP.

Animals↗
PubMed1996

An appraisal of acitretin therapy in children with inherited disorders of keratinization.

Retinoid therapy represents the treatment of choice for severe inherited disorders of keratinization. This paper reviews our experience of acitretin, compares acitretin with etretinate and defines guidelines for treatment. Forty-six children have received acitretin since 1992 in our hospital: 29 children had either lamellar ichthyosis (nine), non-bullous ichthyosiform erythroderma (five), bullous ichthyosiform erythroderma (four), Sjögren-Larsson syndrome (three) or another rare condition (eight). The other 17 children who had psoriasis (16) and extensive viral warts (one), were excluded. Data on efficacy and tolerability of retinoid therapy were available for all but one patient. The cumulative follow-up was 472 months for acitretin. The mean (+/- standard deviation) optimal dosage for acitretin was 0.47 +/- 0.17 mg/kg per day, and this did not significantly differ between disorders. The overall improvement was considerable, with only three patients responding poorly. Mild to moderate mucocutaneous dryness was frequent. Minor abnormalities of liver function tests (four patients) and triglycerides (one patient) never led to changes of therapy. Irreversible side-effects did not occur. Acitretin therapy for children with inherited keratinization disorders is best started at 0.5 mg/kg per day. It represents a safe and effective treatment, provided that the minimal effective dose is maintained and that side-effects are carefully monitored. When switching from etretinate to acitretin, a 20% reduction is recommended if the etretinate dose is over 0.75 mg/kg per day or if side-effects are dose limiting. Otherwise the same dose can be used.

Acitretin↗
PubMed1996

Nance-Sweeney chondrodysplasia--a further case?

A 52-year-old male with short stature due to short limbs, a cleft palate and subcutaneous calcification was described by Nance and Sweeney in 1970. His parents were consanguineous and two female sibs and two cousins were said to be similarly affected, thus the authors proposed that this was a previously undescribed recessively inherited chondrodystrophy. We describe a patient with short stature due to short limbs, subcutaneous calcification, and a cleft palate with features similar to those described by Nance and Sweeney.

Arm↗