Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 96-99).

Les granulocytes neutrophiles sont les cellules immunitaires les plus abondantes dans l'organisme. Elles constituent notre première ligne de défense contre les infections microbiennes. Les personnes neutropéniques sont à haut risque de mortalité en cas d'infections microbiennes graves. Lorsque les traitements antimicrobiens standards sont inefficaces, les patients peuvent recevoir une transfusion de concentré de granulocytes (CG) pour rétablir temporairement un nombre de neutrophiles en circulation permettant d'éradiquer l'infection. Au Canada, les CG sont préparés par Héma-Québec à partir de donneurs stimulés avec une dose de prednisone augmentant le nombre de neutrophiles en circulation. Aux États-Unis le G-CSF sert d'agent de stimulation des donneurs. Les neutrophiles sont récoltés par leucaphérèse et certifiés pour la transfusion selon le nombre de neutrophiles récoltés. Or, ce critère ne reflète pas la viabilité et l'état fonctionnel des cellules transfusées. Notre étude compare la viabilité, le phénotype et les fonctions antimicrobiennes des neutrophiles obtenus des CG dérivés de prednisone et de G-CSF. La prednisone mobilise des neutrophiles matures avec une phagocytose augmentée mais le nombre de neutrophiles est souvent proche de la limite transfusable. Le G-CSF augmente considérablement le nombre de neutrophiles récoltés, dont près de la moitié sont immatures, en plus d'abaisser la chimiotaxie et d'augmenter la production de cytokines. D'après nos résultats, la durée d'entreposage des CG est le paramètre le plus critique pour le maintien de la viabilité et des fonctions antimicrobiennes des neutrophiles, particulièrement pour ceux dérivés du G-CSF alors que la leucaphérèse a un effet négligeable sur les deux types de CG. L'amélioration des processus de fabrication, d'entreposage des CG et leur certification avec un critère fonctionnel permettra de maintenir la viabilité et les fonctions des neutrophiles et d'assurer leur efficacité in vivo. / Neutrophil granulocyte are the most abundant immune cells in the organism. They constitute our first line of defence against invasive pathogens. Neutropenic patients with life-threatening infections can be transfused with granulocyte concentrates (GCs) to temporarily restore a sufficient number of circulating neutrophils to eradicate infection. In Canada, GC are prepared by Héma-Québec from donors pre-treated with a unique dose of prednisone enhancing the number of circulating neutrophils. In the U.S, G-CSF is used as mobilizing agent in the donors. Neutrophils are collected by leukapheresis and certified for transfusion according to the number of neutrophils collected. This criterion, however, does not reflect the viability and the functional capacity of the transfused cells. Our study compare the viability, the phenotype and antimicrobial functions of neutrophils from prednisone and G-CSF-derived GCs. Prednisone mobilizes mature neutrophils with enhanced phagocytosis although the number of collected neutrophils is sometimes below the required transfusion dose of 1 x10¹⁰ granulocytes per unit. G-CSF significantly increases the number of collected neutrophils, though almost half are immature, along with decreasing chemotaxis and increasing cytokine production. According to our results, storage duration is the most critical parameter for the preservation of neutrophils viability and antimicrobial functions, particularly for G-CSF-derived GC neutrophils whereas leukapheresis had negligible effect for both type of GCs. The improvement of GCs supply chain and storage as well as certification based on a functional criterion will allow to preserve the viability and effector functions of neutrophils and guaranty GCs in vivo efficacy.

Dissertation (Ph.D.)--Auburn University, 2005. / Abstract. Vita. Includes bibliographic references.

This study tested the hypothesis that administration of immunosuppressive doses of prednisone in conjunction with ultralow-dose aspirin (0.5 mg/kg/day) would result in gastroduodenal lesion scores similar to those found in dogs administered only immunosuppressive doses of prednisone, but that the gastroduodenal scores from both of these treatment groups would be significantly higher than placebo when administered to healthy dogs for 27 days. Eighteen healthy adult purpose-bred dogs were divided randomly into three groups. Group I received placebo capsules and placebo suspension, Group II received prednisone capsules (mean 2.3 mg/kg, range 2.0-2.4) and placebo suspension, and Group III received prednisone capsules (mean 2.3 mg/kg, range 2.3-2.5) and aspirin suspension (0.5 mg/kg) by mouth once daily for 27 days. Gastroduodenoscopy was performed on days -7 (baseline), 5, 14, and 27 of treatment. Four regions of the stomach (angularis incisura, body, pylorus, and cardia) and the proximal descending duodenum were systematically scored on a scale of 1 (normal) to 11 (perforating ulcer) by an experienced observer who was blinded to the treatment groups and clinical signs of each subject. Dogs were observed every 8 hours for vomiting, diarrhea, and inappetence. Feces were scored on a scale of 1-5 with diarrhea defined as a fecal score <4. Lesion scores for each group, at each location, and total scores, at each time period were evaluated for the effects of time and treatment using a Kruskal-Wallis test. Total dog days of vomiting and dog days of diarrhea in each group were compared using a Wilcoxon rank sums test. Significance was determined at p<0.05. There were no significant differences in median total gastric lesion scores between any of the groups at any time during the study. There was no location effect on regional gastroduodenal lesion scores and there was no significant change in gastroduodenal lesion scores over time in any of the groups during treatment. Significantly more dog-days of diarrhea occurred within the prednisone and aspirin group during the experimental period (Period 2) in comparison to Period 1. However, no significant differences were found between any of the groups for dog-days of vomiting, diarrhea or inappetence at any time in the study. / Master of Science

Differences in cardiovascular/aerobic function in heart transplant patients might be attributed to the rate of corticosteroid withdrawal and/or to skeletal muscle function. This hypothesis was tested among nine male, cardiac transplant recipients. Prednisone dosage was monitored, and isokinetic strength testing was performed at 4 different time periods throughout the first year post-transplantation. Cardiovascular/aerobic measurements were obtained at the fourth time period. Pre-surgery characteristics were obtained from the patient's medical record. Significant Pearson-product moment correlations were only found between muscle function and aerobic function and between pre-surgery characteristics and cardiovascular/aerobic performance. The results of this study show no evidence that rapid reduction of prednisone dosage enhances aerobic function by benefiting skeletal muscle function.

No description available.

Cette étude avait comme objectif d’évaluer la coagulation par l’utilisation de la thrombélastographie (TEG®) et de la génération de thrombine (GT) chez des beagles en santé recevant de la prednisone ainsi que chez des chiens atteints d’hyperadrénocorticisme (HAC). Dans un premier temps, six beagles adultes en santé ont été évalués dans une étude prospective longitudinale au courant de laquelle chaque individu recevait 1 mg/kg/jour de prednisone par la voie orale pendant 2 semaines. Après un arrêt de traitement d’une durée de 6 semaines, ils ont finalement reçu 4 mg/kg/jour de prednisone pour encore 2 semaines. Les tracés TEG® et les mesures de la GT ont été obtenus au temps 0, à la fin des 6 semaines d’interruption de traitement, ainsi qu’à la suite des 2 dosages de prednisone. Suite aux 2 traitements avec la prednisone, des résultats significatifs,lorsque comparés aux valeurs de base, ont été obtenus pour la cinétique du caillot (« clot kinetics » ou K), l’angle alpha (α) et l’amplitude maximale (« maximal amplitude » ou MA). La GT avait augmenté de manière significative mais seulement après la dose de 1 mg/kg/jour de prednisone. Dans un deuxième temps, 16 chiens atteints d’HAC ont été évalués avant l’initiation d’un traitement pour leur condition. Quinze chiens ont été évalués par TEG® et 15 par GT. Les données obtenues ont ensuite été comparées aux valeurs normales. L’analyse par TEG® a démontré que 12/15 chiens avaient au moins un paramètre suggérant un état d’hypercoagulabilité. L’analyse par GT a démontré que 4/15 chiens avaient des changements compatibles avec un état d’hypercoagulabilité. Un test t-pairé pour des valeurs de variance inégales a démontré que le groupe de chiens atteints d’HAC avait des tracés hypercoagulables et un potentiel endogène de thrombine (« endogenous thrombin potential » ou ETP) plus élevé, lorsque comparé à la population de référence. / The purpose of this study was to use thrombelastography (TEG®) and thrombin generation (TG) to evaluate coagulation in healthy beagles receiving oral prednisone as well as client-owned dogs diagnosed with hyperadrenocorticism (HAC).Six healthy adult beagles were used in a prospective ongitudinal study whereby all dogs received 1 mg/kg of prednisone orally once daily for two weeks, followed by a 6-week washout period and then 4 mg/kg of prednisone orally once daily for two weeks. TEG® tracings and TG measurements were obtained at baseline, at the end of the washout period and at the end of both corticosteroid trials. Significant results as compared to baseline were obtained for clot kinetics (K), alpha angle (α)and maximum amplitude (MA), with tracings compatible with a hypercoagulable profile following both corticosteroid trials. Thrombin generation resulted in a significant increase in endogenous thrombin potential (ETP) after the 1 mg/kg/day trial only. Secondly, sixteen dogs affected by HAC were evaluated. Fifteen dogs were evaluated by TEG® and 15 dogs were evaluated by TG before treatment and compared to the normal reference values. For the TEG® analysis, 12/15 dogs had at least one parameter that suggested hypercoagulability. A paired t test for values with unequal variance was used to compare the HAC dogs to the healthy dogs and found that HAC dogs have hypercoagulable TEG® tracings. The same results were found when TG was used with the ETP elevated in the HAC dogs. However, when dogs were evaluated individually, only 4/15 had hypercoagulable TG results.

Cette étude avait comme objectif d’évaluer la coagulation par l’utilisation de la thrombélastographie (TEG®) et de la génération de thrombine (GT) chez des beagles en santé recevant de la prednisone ainsi que chez des chiens atteints d’hyperadrénocorticisme (HAC). Dans un premier temps, six beagles adultes en santé ont été évalués dans une étude prospective longitudinale au courant de laquelle chaque individu recevait 1 mg/kg/jour de prednisone par la voie orale pendant 2 semaines. Après un arrêt de traitement d’une durée de 6 semaines, ils ont finalement reçu 4 mg/kg/jour de prednisone pour encore 2 semaines. Les tracés TEG® et les mesures de la GT ont été obtenus au temps 0, à la fin des 6 semaines d’interruption de traitement, ainsi qu’à la suite des 2 dosages de prednisone. Suite aux 2 traitements avec la prednisone, des résultats significatifs,lorsque comparés aux valeurs de base, ont été obtenus pour la cinétique du caillot (« clot kinetics » ou K), l’angle alpha (α) et l’amplitude maximale (« maximal amplitude » ou MA). La GT avait augmenté de manière significative mais seulement après la dose de 1 mg/kg/jour de prednisone. Dans un deuxième temps, 16 chiens atteints d’HAC ont été évalués avant l’initiation d’un traitement pour leur condition. Quinze chiens ont été évalués par TEG® et 15 par GT. Les données obtenues ont ensuite été comparées aux valeurs normales. L’analyse par TEG® a démontré que 12/15 chiens avaient au moins un paramètre suggérant un état d’hypercoagulabilité. L’analyse par GT a démontré que 4/15 chiens avaient des changements compatibles avec un état d’hypercoagulabilité. Un test t-pairé pour des valeurs de variance inégales a démontré que le groupe de chiens atteints d’HAC avait des tracés hypercoagulables et un potentiel endogène de thrombine (« endogenous thrombin potential » ou ETP) plus élevé, lorsque comparé à la population de référence. / The purpose of this study was to use thrombelastography (TEG®) and thrombin generation (TG) to evaluate coagulation in healthy beagles receiving oral prednisone as well as client-owned dogs diagnosed with hyperadrenocorticism (HAC).Six healthy adult beagles were used in a prospective ongitudinal study whereby all dogs received 1 mg/kg of prednisone orally once daily for two weeks, followed by a 6-week washout period and then 4 mg/kg of prednisone orally once daily for two weeks. TEG® tracings and TG measurements were obtained at baseline, at the end of the washout period and at the end of both corticosteroid trials. Significant results as compared to baseline were obtained for clot kinetics (K), alpha angle (α)and maximum amplitude (MA), with tracings compatible with a hypercoagulable profile following both corticosteroid trials. Thrombin generation resulted in a significant increase in endogenous thrombin potential (ETP) after the 1 mg/kg/day trial only. Secondly, sixteen dogs affected by HAC were evaluated. Fifteen dogs were evaluated by TEG® and 15 dogs were evaluated by TG before treatment and compared to the normal reference values. For the TEG® analysis, 12/15 dogs had at least one parameter that suggested hypercoagulability. A paired t test for values with unequal variance was used to compare the HAC dogs to the healthy dogs and found that HAC dogs have hypercoagulable TEG® tracings. The same results were found when TG was used with the ETP elevated in the HAC dogs. However, when dogs were evaluated individually, only 4/15 had hypercoagulable TG results.

Call number: LD2668 .T4 1985 D42 / Master of Science

INTRODUÇÃO: As infecções pulmonares constituem uma das principais causas de morbidade e mortalidade após o transplante pulmonar. O transplante expõe a árvore brônquica a uma série de condições, como à lesão de secção e anastomose brônquica e à ação dos imunossupressores, alterando os componentes do epitélio mucociliar. O sistema mucociliar presente nas vias aéreas do sistema respiratório é o principal mecanismo de defesa do trato respiratório, assim a influência de drogas neste sistema precisa ser investigada. A prednisona é um importante corticosteróide usado após o transplante de pulmão, no entanto seu uso pode estar associado ao aumento da mortalidade no período pós por complicações como baixa cicatrização e infecções. Desta forma, o objetivo deste estudo foi avaliar os efeitos da secção brônquica e da terapia com prednisona na depuração mucociliar. MÉTODOS: Foram utilizados 180 ratos machos Wistar distribuídos em 6 grupos (P1, P2, P3, ScP2, ScSal e Sal). Os animais dos grupos P1, P2 e P3 receberam diferentes doses de prednisona (0,625, 1,25 e 2,5 mg/kg/dia); os do grupo ScP2 foram submetidos à cirurgia de secção e anastomose brônquica e terapia com 1.25 mg/kg/dia de prednisona; do grupo ScSal foram submetidos à cirurgia de secção e anastomose brônquica e gavagem diária de solução fisiológica; por fim, os animais do grupo Sal receberam gavagem de solução fisiológica. Após o período de tratamento (7, 15 ou 30 dias), os animais foram sacrificados, e as medidas de freqüência de batimento ciliar (FBC), velocidade de transporte mucociliar (VTMC) e transportabilidade do muco (TM) coletadas. Para avaliar os efeitos da droga realizamos a análise estatística comparativa entre os grupos P1, P2, P3 e Sal. Para avaliar a possível interação da droga com o procedimento cirúrgico comparamos os grupos ScP2, ScSal e P2. RESULTADOS: A administração das diferentes doses de prednisona estudadas prejudicaram a TM e a dosagem mais alta (P3) diminuiu a VTMC. Os animais submetidos à secção e anastomose brônquica mostraram redução significativa de VTMC e FBC após 7 e 15 dias da cirurgia (p<0.001) Observamos a recuperação desses parâmetros após 30 dias do procedimento cirúrgico. A droga melhorou a TM dos animais submetidos à secção e anastomose brônquica (p<0,02). CONCLUSÕES: Altas dosagens de prednisona prejudicam a depuração mucociliar. A terapia com prednisona associada à cirurgia de secção e anastomose brônquica não altera a depuração mucociliar visto que, apesar de melhorar a transportabilidade do muco, a freqüência de batimento ciliar e a velocidade de transporte mucociliar não são influenciadas / INTRODUCTION: Infections have been and still are the major cause of morbidity and mortality after lung transplantation. Since mucociliary clearance (MCC) plays an important role on the human defense mechanism, the influence of drugs on MCC of patients submitted to lung transplantation must be examined. Prednisone is the most important corticosteroid used after lung transplantation. The aim of this study was to evaluate the effects of bronchial transection and prednisone therapy (P) on mucociliary clearance. METHODS: 180 rats were assigned to 6 groups (P1, P2, P3, ScSal, e Sal) according to surgical procedure or drug therapy: P1 (0.625mg/kg/day), P2 (1.25 mg/kg/day), P3 (2.5mg/kg/day), ScP2 (bronchial section and reanastomosis + 1.25 mg/kg/day ), Sal (saline solution 2ml/day) and ScSal (bronchial section + saline solution 2ml/day). After 7, 15 or 30 days they were killed and lungs were removed from thoracic cavity. Mucociliary transport velocity (MCTV), ciliary beting frequency (CBF) and mucus transportability (MT) were evaluated. RESULTS: The administration of different doses of prednisone studied harmed MT and the highest dosage (P3) decreased MCTV. FBC and MCTV was significantly impaired 7 and 15 days after bronchial transection and reanastomosis (p<0.001), but they showed a partial recovery on the 30th day after surgery procedure. Prednisone therapy improved MT after surgery procedure (p<0,02). CONCLUSION: High dosages of prednisone affect mucociliary clearance. The Prednisone therapy after section and reanastomosis surgery not affect mucociliary clearance since, despite improving MT, the CBF and MCTV are not influenced