L'implication des polynucléaires neutrophiles (PN) dans l'hémostase n'est pas un concept nouveau, mais requière encore beaucoup d'éclaircissements. Des données attribuent à ces cellules à la fois une capacité à favoriser (voire à déclencher) les mécanismes et une capacité à limiter voire éliminer le caillot de fibrine. Pour expliquer leur implication, une contribution des enzymes granulaires, et essentiellement la cathepsine G (Cath G) et l'élastase (HNE), est fréquemment citée. L'objet de ces travaux est d'étudier chez des sujets sains l'impact des PN humains et des 2 enzymes granulocytaires (Cath G et HNE) sur la coagulation, à l'aide de tests globaux : thromboélastométrie rotative et test de génération de thrombine. Le potentiel procoagulant des PN a aussi été étudié en thrombinographie chez des patients atteints de syndrome myéloprolifératif (SMP) JAK2V617F positif. Dans les systèmes choisis, les PN font preuve d'une activité procoagulante claire, permettant notamment une réduction systématique du temps de coagulation et une augmentation du travail thrombinique total. Cette activité procoagulante est proportionnelle à la concentration en PN et est exacerbée après stimulation préalable par le fMLP, mais elle n'est pas liée à une activité facteur tissulaire. La Cath G et l'HNE permettent également toutes deux une réduction du temps de coagulation, mais elles font preuve à la fois d'effets procoagulants (par inactivation des inhibiteurs comme le TFPI) et anticoagulants (par inactivation du facteur V ou par dégradation de la (du) fibrin(ogèn)e). Enfin, les données de ce travail ne mettent pas en évidence une hypercoagulabilité liée aux PN dans le contexte de SMP. / Polymorphonuclear neutrophils (PMN) are the most abundant nucleated cells in blood. Their involvement in haemostasis – in particular in coagulation and clot formation – is not a new concept, but is not yet fully understood. Many data from the literature indicate that these cells can enhance (even trigger) coagulation, whereas others indicate it can impair fibrin formation and facilitate clot elimination. Among the hypotheses explaining this involvement, attention has focused on PMN granules enzymes, in particular, Cathepsin G (Cath G) and elastase (HNE). We first aim at studying in healthy subjects the impact of PMN as well as Cath G and HNE on coagulation by use of global tests: rotative thromboelastometry (ROTEM®) and thrombin generation test (CAT®). Second, procoagulant potential of PMN is investigated using CAT® in patients affected by myeloproliferative disorders (MPD), with presence of JAK2V617F mutation. Under our conditions, PMN show an unambiguous procoagulant activity, inducing systematically a decrease in clotting time, along with an increase in total thrombin work. This activity is proportional with PMN concentration; fMLP-induced PMN stimulation enhances also it, but this is not related to tissue factor activity. Both Cath G and HNE induce a decrease in clotting time, but support procoagulant (by inactivation of inhibitors such as TFPI) as well as anticoagulant activity (by inactivation of factor V or fibrin(ogen) degradation). At last, data obtained don't show MPD-associated hypercoagulability which can be attributed to PMN.

A dissertation submitted in partial compliance with the requirements for a Master's Degree in Technology: Chiropractic, Technikon Natal, 1999. / The purpose of this study is to determine the relative effectiveness of (Contract-Relax- Agonist-Contract) CRAC stretching, a component of Proprioceptive Neuromuscular facilitated (PNF) stretching, as opposed to static stretching in the treatment of active myofascial trigger points of the shoulder girdle and neck muscles. This was a randomised clinical trial consisting of two groups. Group A received static stretching as their treatment protocol and Group B received PNF (CRAC) as their treatment protocol. Each group consisted of fifteen people between the ages of 18 and 55 who were randomly allocated to their respective groups. It is hypothesised that PNF (CRAC) stretching would be relatively more effective than Static stretching in the treatment of active myofascial trigger points of the shoulder girdle and neck muscles. Subjects diagnosed with active myofascial trigger points in the Trapezius, Infraspinatus and Rhomboid muscles were included in the study. The treatment regime consisted of a course of five treatments spread over a period of two weeks and then a one - month follow up consultation. Subjective and objective measurements were taken at the first, fifth and follow up consultations. Subjective data consisted of the Short Form McGill Pain Questionnaire, the CMCC Neck Disability Index and the Numerical Pain Rating Scale -101. The objective data was collected by means of algometer and goniometer measurements. This data was used to perform statistical analysis using the non-parametric Wilcoxin signed-rank test and the Mann Whitney unpaired test to compare intra-group and intergroup data respectively, at a 95% confidence level. This study suggests that both static and PNF (CRAC) stretching are effective in the treatment of active myofascial trigger points. However there is no clinical statistical difference between these two treatments. Further studies with a larger sample size are needed to clearly evaluate the use of stretching in the treatment of active myofascial trigger points. / M

Master of Science (Medicine) / Clinical studies have demonstrated an arousal deficit in infants suffering Obstructive Sleep Apnoea (OSA), and that treatment to alleviate the symptoms of OSA appears to reverse the deficit in arousability. Some sudden infant deaths are thought to be contingent upon such an arousal deficit. This research utilised young piglets during early postnatal development, and exposed them to intermittent hypercapnic hypoxia (IHH) as a model of clinical respiratory diseases. Arousal responses of control animals were compared to the animals exposed to IHH. Comparisons were also made between successive exposures on the first and the fourth consecutive days of IHH. Time to arouse after the onset of the respiratory stimulus, and frequency of arousals during recovery, demonstrated that arousal deficits arose after successive exposures and that these were further exacerbated on the fourth study day. After an overnight recovery period, the arousal deficit was apparently dormant, and only triggered by HH exposure. These studies confirm that both acute and chronic deficits can be induced on a background of otherwise normal postnatal development, suggesting that deficits observed in the clinical setting may be a secondary phenomenon.

Hypoxia is a common feature of many respiratory disorders including acute severe asthma, chronic obstructive pulmonary disease and pneumonia. Hypoxia also occurs during sleep - disordered breathing in conditions such as sleep hypoventilation syndrome and sleep apnea. In most respiratory diseases hypoxia is coupled with increased respiratory load. Compensatory protective mechanisms are activated to oppose these impediments to respiration. However, hypoxia is associated with impaired neurocognitive function and recent studies have demonstrated that hypoxia suppresses respiratory load perception in healthy individuals and asthma patients. These recent findings raise the possibility that a variety of protective physiological reflex responses to increased respiratory load may be impaired during periods of hypoxia. The effects of hypoxia on several of these protective responses and possible mechanisms of respiratory sensory depression by hypoxia are explored in the experiments outlined in this thesis. In the first study, the respiratory related evoked potential ( RREP ) was used to investigate the mechanisms underlying hypoxia - induced suppression of respiratory load sensation in healthy individuals. As a positive control the effects of hypoxia on respiratory load perception to inspiratory resistive loads were also measured. The amplitude of the first and second positive peaks ( P1 and P2 ) of the RREP were significantly reduced during hypoxia. P1 is thought to reflect the arrival of the ascending respiratory signals to the somatosensory area of the cortex. The perceived magnitude of externally applied inspiratory resistive loads was also reduced during hypoxia. These data provide further support that hypoxia suppresses respiratory load perception and suggest that this is mediated, at least in part, by suppression of respiratory afferent information prior to its arrival at the cortex. In the second study, the effects of acute sustained hypoxia on the cough reflex threshold and cough tachyphylaxis to inhaled capsaicin were explored in healthy individuals. Acute sustained hypoxia suppressed cough reflex sensitivity to inhaled capsaicin. This finding raises the possibility that the cough reflex, important for protecting the lungs from inhalation or aspiration of potentially injurious substances and for clearing excess secretions, may be impaired during acute exacerbations of hypoxic - respiratory disease. In the third study, reflex responses of the genioglossus and scalene muscles to brief pulses of negative airway pressure were compared between hypoxia and normoxia during wake and sleep in healthy males in the supine position. Cortical RREPs to the same stimuli were also examined under these conditions. The genioglossus is the largest upper airway ( UA ) dilator muscle and can be reflexively augmented in response to negative UA pressure. A diminished response of this muscle during sleep has been postulated to be a contributing mechanism to obstructive sleep apnea ( OSA ) in individuals with an anatomically narrow UA. Cortical activation ( i.e. arousal ) to sudden airway narrowing in OSA is an important protective response to help restore ventilation during an obstructive event. In this study, genioglossus reflex responses to negative pressure pulse stimuli were maintained during mild overnight hypoxia. Conversely, reflex inhibition of the scalene muscle to the same stimuli was prolonged during hypoxia. In addition, a previously undescribed morphology of the genioglossus negative pressure reflex consisting of activation followed by suppression was observed with greater suppression during sleep than wake. The amplitude of the P2 component of the RREP was also significantly reduced during hypoxia. In summary, the potential mechanisms underlying hypoxia - induced suppression of respiratory load sensation and the effects of hypoxia on several protective respiratory responses have been investigated in healthy subjects. The potential implications of these findings for patients with hypoxic - respiratory disease are discussed. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2006.

Thesis (Ph. D.)--Case Western Reserve University, 2007. / [School of Medicine] Department of Epidemiology and Biostatistics. Includes bibliographical references. Available online via OhioLINK's ETD Center.

Thèse de doctorat : Génétique humaine : Paris 12 : 2005. / Titre provenant de l'écran-titre. Bibliogr. : 210 réf.

Thèse de doctorat : Physiopathologie de l'appareil respiratoire et des vaisseaux : Paris 12 : 2005. / Titre provenant de l'écran-titre. Bibliogr. f. 154-172.

Reproduction de : Thèse d'exercice : Médecine. Médecine interne : Nantes : 2008. / Bibliogr.

Reproduction de : Thèse de doctorat : Pharmacologie cardiovasculaire : Lyon 1 : 2006. / Titre provenant de l'écran titre. Bibliogr. f. 149-170.

Thesis (Ph. D.)--University OF MICHIGAN.