Thèses : « Chronic and acute diseases »

1

Stewart, Simon. « Optimising therapeutic efficacy in acute and chronic cardiac disease states / ». Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phs851.pdf.

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2

White, David James. « Haemophilus in acute and chronic respiratory disease ». Thesis, Liverpool John Moores University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304425.

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3

Wei, Jin. « Acute Kidney Injury and Chronic Kidney Disease ». Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/6780.

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Ischemia and reperfusion are natural steps during kidney transplantation, and IRI is considered one of the most important nonspecific factors affecting allograft dysfunction. Transplanted organs experience several episodes of ischemia, in which cold ischemia occurs during allograft storage in preservation solutions. Even though cold ischemia has been studied extensively, all of the studies have been carried out in vitro and ex vivo models. There is no in vivo model available to examine renal IRI induced solely by cold ischemia. In the present study, we developed an in vivo mouse model to study renal IRI induced exclusively by cold ischemia through clamping the renal pedicle for 1 to 5 hours. During the ischemic phase, blood was flushed from the kidney with cold saline through a small opening on the renal vein. The kidney was kept cold in a kidney cup with circulating cooled saline, while the body temperature was maintained at 37℃ during the experiment. The level of kidney injury was evaluated by plasma creatinine, KIM-1, NAGL, GFR, and histology. Plasma creatinine was significantly increased from 0.15±0.04 mg/dl in the sham group to 1.14±0.21 and 2.65±0.14 mg/dl in 4 and 5-hours ischemia groups at 24 hours after cold IRI. The plasma creatinine in mice with ischemic time <3 hours demonstrated no significant increase compared with sham mice. Changes in KIM-1, NAGL, GFR and histology were similar to plasma creatinine. 65 In summary, we developed and characterized a novel in vivo IRI-induced AKI mouse model exclusively produced by cold ischemia.

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4

Rota, Cinzia. « Effect of foetal and adult stem cells in acute and chronic kidney diseases ». Thesis, Open University, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.594841.

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Acute kidney injury (AKl) and chronic kidney disease (CKD) are serious illnesses associated to high mortality and unsatisfactory therapeutic treatments. In search for new therapies, it has become evident that stem cells could be a possible option for patients with AKI and CKD. The evidence of the reno protective effect of bone marrow-mesenchymal stem cells (BM-MSCs) in experimental model of AKl, prompted us to study the effect of stem cells isolated from sources that are more accessible as cord blood (CB) and amniotic fluid. Infusion of hCB-MSCs in inununodeficient mice with AKI ameliorated renal function and tubular structure, prolonging survival. Moreover, transplanted hCB-MSCs localized in peritubular areas, limiting oxidative stress and apoptosis. By virtue of stem cell capacity to produce growth factors, hCB-MSCs were able- to induce the pro-survival factor Akt in tubular cells and subsequently their proliferation. Using the well-established model of AKI in immunodeficient mice, we studied the pro-regenerative effect of amniotic fluid stem (hAFS) cells. Infusion of hAPS cells in cisplatin-mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. These cells engrafted injured kidney predominantly in peri tubular region and through a paracrine mechanism are able to exert an anti-apoptotic effect, to activate AId and stimulate proliferation of tubular cells. We enhanced the therapeutic potential of hAFS cells by cell pretreatment with GDNF, which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartnent. In AKI models, the renoprotective effect of BM-MSCs is well established, however the role of these stem cells in model of eKD is controversial and not demonstrated so far. Therefore, we tested the effect of BM-MSCs in a model of adriarnycin-induced nephropathy. Repeated infusions of BMMSCs limited podocyte loss, and normalized distribution of parietal epithelial cells along the Bowman's capsule, reducing glomerulosclerosis. Moreover, through the local release of growth factors as VEGF, BM-MSCs were able to provide a local pro-survival environment that limited glomerular inflanunation and microvascular rarefaction.

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5

何美美 et Mai-mai Ho. « A study on the acute and chronic effects of morphine on rat stomachs ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1986. http://hub.hku.hk/bib/B31230611.

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Bevan, Damon. « Cytokine involvement in ultraviolet (UV) B induced chronic and acute inflammation in porcine skin ». Thesis, Royal Veterinary College (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300963.

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7

Phan, Thanh Huyen. « Development of therapeutic extracellular vesicles for the treatment of acute and chronic lung diseases ». Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/28760.

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Acute and chronic lung diseases are among the most common causes of disability and death worldwide, which consequently contribute a substantial burden for health and economic system. Chronic obstructive pulmonary disease (COPD) – one type of chronic lung diseases – is a complicated and life-threatening disease. Despite considerable efforts toward developing treatments for COPD, there are currently no effective treatments to resolve this disease. The only available treatments are supportive, and they either allow for temporary relief of several symptoms of COPD such as dyspnoea, cough, and sputum, or reduce exacerbations. Hence, there is an urgent need for a new regenerative medicine approach that can promote the repair/regeneration process in lungs. In the context of tissue regeneration, extracellular vesicles (EVs) are considered as the next generation therapeutics, which can regenerate and restore the function of lung tissue that has been damaged by a disease or injury. However, very few EV-therapeutics can progress to clinical trials due to (a) the lack of standardisation of EV production, and (b) the lack of appropriate lung models to validate the therapeutic effects of EVs. Hence, to accelerate the clinical translation of EV-therapeutics to resolve COPD, the presented work in this thesis was divided into two stages: 1. Development of EV-therapeutics and establishing quality control protocol for EVs to ensure their safety and efficacy in treating COPD. 2. Establishing pre-clinical models to enable testing and validation of the efficacy of EV-therapeutics in treating COPD. This research provided an innovative methodology to produce and comprehensively characterise EVs, which offers a new means to understand the role of EVs in numerous biological processes and disease mechanisms. Moreover, this research would bring significant benefits to global healthcare by accelerating the development of EV-therapeutics for the treatment of lung diseases.

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8

Brocca, Alessandra. « Characterization of molecular pathways involved in acute and acute-on-chronic liver disease ». Doctoral thesis, Università degli studi di Padova, 2017. http://hdl.handle.net/11577/3425355.

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Introduction: Acute decompensation was defined as the acute development of one or more major complications of liver disease and it was the main cause of hospitalization in patients with cirrhosis. The acute-on-chronic liver failure (ACLF) was characterized by acute decompensation of cirrhosis, organ failure and high 28-day mortality. ACLF displayed key features of systemic inflammation and its poor outcome was closely associated with exacerbated systemic inflammatory responses. Inflammasomes were multiprotein complexes which proteolytically activates the cytokines IL-1β and IL-18. These substrates might have an effect on the development of liver disease. Extracellular vesicles (EVs) were involved in many important biological processes as well as in disease pathogenesis. The dynamics of EVs secretion by different cell types and how the secreted EVs interact to advance the pathogenesis of liver disease were still unknown. Aims: The aim of this study was to characterize the molecular pathways involved in acute decompensation of cirrhosis and ACLF through: the characterization of the inflammatory profile of patients, the in vitro evaluation of cytotoxic effects of plasma from patients on renal tubular cells, the expression of Inflammasome in these treated cells and in Peripheral Blood Mononuclear Cells (PBMC) of patients, the characterization of EVs from patients and the study of in vitro effects of isolated EVs in renal tubular cells. Material and Methods: We enrolled patients with compensated cirrhosis, acute decompensation in cirrhosis, ACLF and healthy subjects as control population. Plasma levels of IL-6, IL-1β and IL-18 were detected by ELISA assay. Cytotoxic effects of plasma on renal tubular cells were assayed by annexin V and propidium iodide kit. Inflammasomes expression was detected both in renal tubular cells treated and in PBMC extracted from patients by Real Time PCR. Plasma EVs were extracted by ultracentrifugation and concentration was measured by Nanosight. Characterization of EVs was performed by FACS analysis. Cytotoxic effects of plasma EVs on renal tubular cells were assayed by XTT assay. Results: Plasma levels of pro-inflammatory cytokines measure in the firsts patients enrolled did not differed between the groups of compensated cirrhosis, acute decompensation and ACLF. Also viability and death rate did not change in a way statistically significant in cell stimulated with plasma from the three groups of patients. Furthermore, Inflammasome gene expression in these cells did not underlines the activation of this protein complex. In PBMC from patients, gene expression of Tool-like receptor 2 (TLR-2) was significantly higher in patients with compensated cirrhosis compare to acute decompensation of cirrhosis (p=0.036). Albumin added to cell medium reduced cytotoxic effects of plasma on renal tubular cells. Plasma EVs of patients enrolled were more concentrated in ACLF groups compare to healthy subjects. EVs did not expressed selected platelets (CD41, CD42b) and monocyte markers (CD14) in their surface but they expressed marker of platelets activated endothelium (CD62E). The levels of CD62E were significantly higher in patients with ACLF compare to healthy subjects and patients with compensated cirrhosis (p=0.0041 and p=0.0111, respectively). CD40L levels were significantly higher in all patients' groups compare to healthy subjects (p<0.02). Plasma EVs from patients with acute and acute-on-chronic liver failure exerted a higher cytotoxic effects compare to healthy subjects and patients with compensated cirrhosis on renal tubular cells (p<0.0001). Cells incubated with EVs from acute and acute-on-chronic liver failure underwent to apoptosis (p<0.0001), to ROS production (p<0.0001), to lose albumin intake capabilities (p<0.0001) and reduction of Zonula Occludens-1 (ZO-1) expression (p=0.0166) compare to healthy subjects and patients with compensated cirrhosis. Instead, megalin and PGC1α expression did not change. Conclusions: The role of EVs in decompensated cirrhosis and ACLF need to be invastigated and study their hypothetic role as vehicle of mediator of extrahepatic organ injury and complications of cirrhosis.
Introduzione: Lo scompenso acuto in cirrosi è definito come la progressione acuta di una o più gravi complicanze della patologia epatica ed è la principale causa di ospedalizzazione nei pazienti con cirrosi. L'insufficienza epatica acuta su cronica (ACLF) è caratterizzata da uno scompenso acuto della cirrosi, da danno d'organo e da un elevato tasso di mortalità a 28 giorni. L'ACLF è caratterizzato da infiammazione sistemica e l'outcome infausto è strettamente associato con l'eccessiva risposta infiammatoria che si attiva nel paziente. L'inflammasoma è un complesso multi-proteico che attiva, mediante taglio proteolitico, citochine pro-infiammatorie come IL-1β e IL-18. Queste, hanno un ruolo nello sviluppo della patologia epatica. Le vescicole extracellulari (EVs) sono coinvolte in molti processi biologici importanti, sia fisiologici che patologici. Il processo di secrezione delle EVs da diversi tipi di cellule e la loro azione nel modulare l'avanzamento della patogenesi nella malattia epatica, non sono ancora completamente chiariti. Scopo: Lo scopo di questo studio è caratterizzare la via del segnale coinvolta nello scompenso acuto della cirrosi e dell'insufficienza epatica acuta-su-cronica attraverso: la caratterizzazione del profilo infiammatorio dei pazienti arruolati, lo studio in vitro dell'effetto citotossico nel plasma dei pazienti nelle cellule tubulari renali (RTC), lo studio dell'espressione dell'inflammasoma nelle cellule trattate e nelle cellule mononucleate del sangue periferico (PBMC) estratte dai pazienti, la caratterizzazione delle EVs estratte dal plasma dei pazienti arruolati e lo studio del loro effetto in vitro su colture di RTC. Materiali e Metodi: sono stati arruolati pazienti con cirrosi compensata, scompenso acuto in cirrosi, insufficienza epatica acuta-su-cronica e una popolazione di volontari sani come controllo. I livelli plasmatici di IL-6, IL-1β e IL-18 sono stati misurati con kit ELISA. L'effetto citotossico del plasma nelle RTC è stato testato con il kit costituito da annexina V e propidio ioduro. Il livello di espressione delle molecole dell'inflammasoma è stato determinato sia nelle cellule stimolate con il plasma, sia nei PBMC estratti dai pazienti, attraverso Real Time Poly Chain Reaction (RT-PCR). Le EVs plasmatiche sono state estratte mediante ultracentrifugazione e la loro concentrazione determinata con il Nanosight. La loro caratterizzazione è stata eseguita mediante analisi al FACS. L'effetto citotossico delle EVs sulle RTC è stato determinato mediante saggio XTT. Risultati: I livelli plasmatici delle citochine pro-infiammatorie, misurati nei primi pazienti arruolati, non mostra differenze tra i gruppi di pazienti con cirrosi compensata, scompensata e insufficienza epatica acuta-su-cronica. Anche la vitalità e la morte cellulare nelle colture stimolate con i plasma dei pazienti arruolati non hanno mostrato un profilo peculiare dei gruppi testati e non è stata riscontrata attivazione della trascrizione delle molecole dell'inflammasoma. L'espressione del Tool-like receptor 2 (TLR-2) nei PBMC si è dimostrata significativamente elevata nei pazienti con cirrosi compensata rispetto a quelli con scompenso acuto (p=0,036). Aggiungendo albumina al mezzo di coltura cellulare si è notata una riduzione dell'effetto citotossico del plasma dei pazienti nelle RTC. La concentrazione plasmatica di EVs risulta maggiore nei pazienti con insufficienza epatica acuta-su-cronica rispetto ai controlli sani. Le vescicole non esprimono i marcatori tipici piastrinici (CD41 e CD42b) e monocitari (CD14) sulla loro superficie ma esprimono il marcatore dell'epitelio attivato da piastrine (CD62E). I livelli di CD62E sono significativamente elevati nei pazienti con insufficienza eparica acuta-su-cronica rispetto ai controlli sani e ai pazienti con cirrosi compensata (p=0,0041 e p=0,0111, rispettivamente). I livelli di CD40L sono significativamente elevati in tutti i gruppi di pazienti rispetto ai controlli sani (p<0,02). Le EVs isolate dei pazienti con insufficienza epatica acuta-su-cronica hanno un effetto citotossico superiore rispetto a quelle dei controlli sani e dei pazienti con cirrosi compensata nelle RTC (p<0,0001). Le cellule incubate con le EVs da pazienti con scompenso acuto in cirrosi e insufficienza epatica acuta-su-cronica vanno incontro ad apoptosi (p<0,0001), a produzione massiccia di ROS (p<0,0001), alla perdita della capacità di internalizzare l'albumina (p<0,0001) e alla riduzione dell'espressione di Zonula Occludens-1 (ZO-1) (p=0,0166) rispetto ai soggetti sani e ai pazienti con cirrosi compensata. Non si osserva invece un cambiamento nell'espressione cellulare di megalina e PGC1α. Conclusioni: Il ruolo delle EVs nella cirrosi scompensata necessita di essere approfondito perché potrebbero rappresentare il veicolo su cui viaggiano i mediatori del danno d’organo extraepatico.

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Lo, Iek-long, et 羅奕龍. « Impacts of cognitive impairment on acute exacerbations of chronic obstructive pulmonary disease among Chinese elderly patients ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45830770.

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10

Chen, Roy Yu-Wei. « Biomarkers for acute exacerbation of chronic obstructive pulmonary disease ». Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/57759.

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Rationale: There are currently no generally accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD). There is an urgent need of biomarkers that can guide therapeutic management in AECOPD. Based on literature review, systemic inflammation and mild cardiac dysfunction are often associated with AECOPD. We hypothesized that certain protein markers can indeed be useful in tracking and diagnosing AECOPD progression. Methods: The study cohort consisted of 368 patients recruited in the chronic obstructive pulmonary disease (COPD) Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 76 stable COPD patients who served as controls. We first determined the relationship of AECOPD of C-reactive protein (CRP) and the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP). We then performed a discriminatory analysis using receiver-operating characteristics (ROC) curve in a logistic regression model. We compared the area under the curve (AUC) of 4 different combinations of CRP and NT-proBNP models. Lastly, we examined several potential biomarkers that were implicated in AECOPD. Results: The demographic data of the cohort and the controls were well matched, with an average age of 68 versus 65 years old, 64% versus 77% male, and a forced expiratory volume in 1 second (FEV1) % predicted of 52% versus 58%. The CRP and NT-proBNP levels at exacerbation onset were found to be the highest and progressively decreased over time. Of the 4 models of ROC curves, the leave-one-out cross-validated model including both CRP and NT-proBNP had an AUC of 0.80. This model replicated well in an external LEUKO dataset. On the ii other hand, D-Dimer, pulmonary and activation-regulated chemokine (PARC) and troponin I, showed minimal or no temporal changes during hospitalization and were no different than those with stable COPD. Conclusions: In summary, this thesis demonstrated that biomarkers such as CRP and NT-proBNP are significantly elevated during AECOPD and decreased with recovery. Secondly, a combination of CRP and NT-proBNP could discriminate patients who were hospitalized for their AECOPD from stable patients. Together, these two biomarkers show promise in diagnosing and tracking AECOPD.
Medicine, Faculty of
Medicine, Department of
Experimental Medicine, Division of
Graduate

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11

Harbord, Marcus William Nixon. « Investigation of acute inflammation in Crohn's disease and chronic granulomatous disease ». Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399572.

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12

Reavell, Colleen Frances. « Resolution of muscle wasting during an acute exacerbation of chronic obstructive pulmonary disease (COPD) ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0031/MQ64435.pdf.

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13

Chin, Elizabeth D. « Symptom Experience and Treatment Delay during Acute Exacerbation of Chronic Obstructive Pulmonary Disease : A Dissertation ». eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsn_diss/30.

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Chronic obstructive pulmonary disease (COPD) is a major health problem in the United States. Acute exacerbations of COPD are primarily responsible for the physical, psychological and economic burden of this disease. Early identification and treatment of exacerbations is important to improve patient and healthcare outcomes. Little is known about how patients with COPD recognize an impending exacerbation and subsequently decide to seek treatment. The purpose of this qualitative descriptive study was to explore and describe symptom recognition and treatment delay in individuals experiencing an acute exacerbation of chronic obstructive pulmonary disease (COPD). Leventhal’s Common Sense Model of illness representation undergirded this study. Using semi-structured interviews, adults hospitalized with an acute exacerbation of COPD were asked to describe their symptom experience and self care behaviors, including treatment seeking, in the days to weeks prior to hospitalization. Data analysis revealed one main theme: Recognizing, responding and reacting to change, and six subthemes: Something’s coming, Here we go again, Seeking urgent treatment, Riding it out, Not in charge anymore and My last day that richly described the COPD exacerbation experience. The study revealed that patients experience an illness prodrome prior to exacerbation and have a recurrent exacerbation symptom pattern that was self-recognized. Treatment seeking was most influenced by the speed and acuity of exacerbation onset, severity of breathlessness, fears of death, nature of patient-provider relationship and the perception of stigmatization during prior healthcare encounters. These findings are important for the development of interventions to improve patient recognition and management of COPD exacerbations in the future.

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Wong, May Yue Wai. « Novel anti-fibrotic agents in acute and chronic kidney disease ». Thesis, The University of Sydney, 2020. https://hdl.handle.net/2123/22015.

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The thesis spans the spectrum of causative and therapeutic aspects of chronic kidney disease (CKD), which is a significant and growing health burden. While it is desirable that these findings will translate into effective strategies to prevent CKD, kidney impairment is frequently diagnosed when advanced renal fibrosis has already developed. Thus, the second part of this thesis focuses on therapy and explores whether anti-inflammatory or anti fibrotic agents such as semicarbazide sensitive amine oxidase (SSAO) inhibitor or cationic-independent mannose 6-phosphate receptor (CI-6MPR) inhibitors show renoprotection and therefore proof of concept to develop as novel treatments. SSAO was studied in early renal fibrosis after unilateral ureteral obstruction (UUO) and in a diabetic mouse model that mimics the development of human diabetic kidney disease (DKD). Inhibition of SSAO with a highly selective, small molecule inhibitor reduced markers of extracellular matrix (ECM) deposition in the UUO model. Importantly, SSAO inhibition resulted in amelioration of proteinuria and glomerulosclerosis in the diabetic mice. It thus had a beneficial effect on preserving glomerular structure and function. We conclude that it may be a promising therapeutic strategy to limit the development of DKD and renal fibrosis of other aetiologies. CI-6MPR inhibition was studied in a UUO model and demonstrated a lower tubulointerstitial fibrosis index, collagen IV and fibronectin protein and mRNA expression when compared to untreated UUO mice. These results pave the way for translational studies in humans.

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Sabapathy, Surendran, et n/a. « Acute and Chronic Adaptations To Intermittent and Continuous Exercise in Chronic Obstructive Pulmonary Disease Patients ». Griffith University. School of Physiotherapy and Exercise Science, 2006. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20070115.170236.

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The primary aim of this thesis was to develop a better understanding of the physiology and perceptual responses associated with the performance of continuous (CE) and intermittent exercise (IE) in patients with moderate chronic obstructive pulmonary disease (COPD). A secondary aim was to examine factors that could potentially limit exercise tolerance in COPD patients, particularly in relation to the dynamics of the cardiovascular system and muscle metabolism. The results of the four studies conducted to achieve these aims are presented in this thesis. In Study 1, the physiological, metabolic and perceptual responses to an acute bout of IE and CE were examined in 10 individuals with moderate COPD. Each subject completed an incremental exercise test to exhaustion on a cycle ergometer. Subjects then performed IE (1 min exercise: 1 min rest ratio) and CE tests at 70% of peak power in random order on separate days. Gas exchange, heart rate, plasma lactate concentration, ratings of breathlessness, inspiratory capacity and the total amount of work completed were measured during each exercise test. Subjects were able to complete a significantly greater amount of work during IE (71 ± 32 kJ) compared with CE (31 ± 24 kJ). Intermittent exercise was associated with significantly lower values for oxygen uptake, expired ventilation and plasma lactate concentration when compared with CE. Subjects also reported a significantly lower rating of breathlessness during IE compared to CE. The degree of dynamic lung hyperinflation (change in end-expiratory lung volume) was lower during IE (0.23 ± 0.07 L) than during CE (0.52 ± 0.13 L). The results suggest that IE may be superior to CE as a mode of training for patients with COPD. The greater amount of total work performed and the lower measured physiological responses attained with intermittent exercise could potentially allow greater training adaptations to be achieved in individuals with more limited lung function. The purpose of Study 2 was to compare the adaptations to 8 wk of supervised intermittent and continuous cycle ergometry training, performed at the same relative intensity and matched for total work completed, in patients with COPD. Nineteen subjects with moderate COPD were stratified according to age, gender, and pulmonary function, and then randomly assigned to either an IE (1 min exercise: 1 min rest ratio) or CE training group. Subjects trained 3 d per week for 8 wk and completed 30 min of exercise. Initial training intensity, i.e., the power output applied during the CE bouts and during the exercise interval of the IE bouts, was determined as 50% of the peak power output achieved during incremental exercise and was increased by 5% each week after 2 wk of training. The total amount of work performed was not significantly different (P=0.74) between the CE (750 ± 90 kJ) and IE (707 ± 92 kJ) groups. The subjects who performed IE (N=9) experienced significantly lower levels of perceived breathlessness and lower limb fatigue during the exercise-training bouts than the group who performed CE (N=10). However, exercise capacity (peak oxygen uptake) and exercise tolerance (peak power output and 6-min walk distance) improved to a similar extent in both training groups. During submaximal constant-load exercise, the improved (faster) phase II oxygen uptake kinetic response with training was independent of exercise mode. Furthermore, training-induced reductions in submaximal exercise heart rate, carbon dioxide output, expired ventilation and blood lactate concentrations were not different between the two training modes. Exercise training also resulted in an equivalent reduction for both training modes in the degree of dynamic hyperinflation observed during incremental exercise. Thus, when total work performed and relative intensity were the same for both training modes, 8 wk of CE or IE training resulted in similar functional improvements and physiological adaptations in patients with moderate COPD. Study 3 examined the relationship between exercise capacity (peak oxygen uptake) and lower limb vasodilatory capacity in 9 patients with moderate COPD and 9 healthy age-matched control subjects. While peak oxygen uptake was significantly lower in the COPD patients (15.8 ± 3.5 mL·min-1·kg-1) compared to the control subjects (25.2 ± 3.5 mL·kg-1·min-1), there were no significant differences between groups in peak calf blood flow or peak calf conductance measured 7 s post-ischemia. Peak oxygen uptake was significantly correlated with peak calf blood flow and peak conductance in the control group, whereas there was no significant relationship found between these variables in the COPD group. However, the rate of decay in blood flow following ischemia was significantly slower (p less than 0.05) for the COPD group (-0.036 ± 0.005 mL·100 mL-1·min-1·s-1) when compared to the control group (-0.048 ± 0.015 mL·100 mL-1·min-1·s-1). The results of this study suggest that the lower peak exercise capacity in patients with moderate COPD is not related to a loss in leg vasodilatory capacity. Study 4 examined the dynamics of oxygen uptake kinetics during high-intensity constant-load cycling performed at 70% of the peak power attained during an incremental exercise test in 7 patients with moderate COPD and 7 healthy age-matched controls. The time constant of the primary component (phase II) of oxygen uptake was significantly slower in the COPD patients (82 ± 8 s) when compared to healthy control subjects (44 ± 4 s). Moreover, the oxygen cost per unit increment in power output for the primary component and the overall response were significantly higher in patients with COPD than in healthy control subjects. A slow component was observed in 5 of the 7 patients with COPD (49 ± 11 mL·min-1), whereas all of the control subjects demonstrated a slow component of oxygen uptake (213 ± 35 mL·min-1). The slow component comprised a significantly greater proportion of the total oxygen uptake response in the healthy control group (18 ± 2%) than in the COPD group (10 ± 2%). In the COPD patients, the slow component amplitude was significantly correlated with the decrease in inspiratory capacity (r = -0.88, P less than 0.05; N=5), indicating that the magnitude of the slow component was larger in individuals who experienced a greater degree of dynamic hyperinflation. This study demonstrated that most patients with moderate COPD are able to exercise at intensities high enough to elicit a slow component of oxygen uptake during constant-load exercise. The significant correlation observed between the slow component amplitude and the degree of dynamic hyperinflation suggests that the work of breathing may contribute to the slow component in patients with COPD.

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Sabapathy, Surendran. « Acute and Chronic Adaptations To Intermittent and Continuous Exercise in Chronic Obstructive Pulmonary Disease Patients ». Thesis, Griffith University, 2006. http://hdl.handle.net/10072/366117.

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The primary aim of this thesis was to develop a better understanding of the physiology and perceptual responses associated with the performance of continuous (CE) and intermittent exercise (IE) in patients with moderate chronic obstructive pulmonary disease (COPD). A secondary aim was to examine factors that could potentially limit exercise tolerance in COPD patients, particularly in relation to the dynamics of the cardiovascular system and muscle metabolism. The results of the four studies conducted to achieve these aims are presented in this thesis. In Study 1, the physiological, metabolic and perceptual responses to an acute bout of IE and CE were examined in 10 individuals with moderate COPD. Each subject completed an incremental exercise test to exhaustion on a cycle ergometer. Subjects then performed IE (1 min exercise: 1 min rest ratio) and CE tests at 70% of peak power in random order on separate days. Gas exchange, heart rate, plasma lactate concentration, ratings of breathlessness, inspiratory capacity and the total amount of work completed were measured during each exercise test. Subjects were able to complete a significantly greater amount of work during IE (71 ± 32 kJ) compared with CE (31 ± 24 kJ). Intermittent exercise was associated with significantly lower values for oxygen uptake, expired ventilation and plasma lactate concentration when compared with CE. Subjects also reported a significantly lower rating of breathlessness during IE compared to CE. The degree of dynamic lung hyperinflation (change in end-expiratory lung volume) was lower during IE (0.23 ± 0.07 L) than during CE (0.52 ± 0.13 L). The results suggest that IE may be superior to CE as a mode of training for patients with COPD. The greater amount of total work performed and the lower measured physiological responses attained with intermittent exercise could potentially allow greater training adaptations to be achieved in individuals with more limited lung function. The purpose of Study 2 was to compare the adaptations to 8 wk of supervised intermittent and continuous cycle ergometry training, performed at the same relative intensity and matched for total work completed, in patients with COPD. Nineteen subjects with moderate COPD were stratified according to age, gender, and pulmonary function, and then randomly assigned to either an IE (1 min exercise: 1 min rest ratio) or CE training group. Subjects trained 3 d per week for 8 wk and completed 30 min of exercise. Initial training intensity, i.e., the power output applied during the CE bouts and during the exercise interval of the IE bouts, was determined as 50% of the peak power output achieved during incremental exercise and was increased by 5% each week after 2 wk of training. The total amount of work performed was not significantly different (P=0.74) between the CE (750 ± 90 kJ) and IE (707 ± 92 kJ) groups. The subjects who performed IE (N=9) experienced significantly lower levels of perceived breathlessness and lower limb fatigue during the exercise-training bouts than the group who performed CE (N=10). However, exercise capacity (peak oxygen uptake) and exercise tolerance (peak power output and 6-min walk distance) improved to a similar extent in both training groups. During submaximal constant-load exercise, the improved (faster) phase II oxygen uptake kinetic response with training was independent of exercise mode. Furthermore, training-induced reductions in submaximal exercise heart rate, carbon dioxide output, expired ventilation and blood lactate concentrations were not different between the two training modes. Exercise training also resulted in an equivalent reduction for both training modes in the degree of dynamic hyperinflation observed during incremental exercise. Thus, when total work performed and relative intensity were the same for both training modes, 8 wk of CE or IE training resulted in similar functional improvements and physiological adaptations in patients with moderate COPD. Study 3 examined the relationship between exercise capacity (peak oxygen uptake) and lower limb vasodilatory capacity in 9 patients with moderate COPD and 9 healthy age-matched control subjects. While peak oxygen uptake was significantly lower in the COPD patients (15.8 ± 3.5 mL·min-1·kg-1) compared to the control subjects (25.2 ± 3.5 mL·kg-1·min-1), there were no significant differences between groups in peak calf blood flow or peak calf conductance measured 7 s post-ischemia. Peak oxygen uptake was significantly correlated with peak calf blood flow and peak conductance in the control group, whereas there was no significant relationship found between these variables in the COPD group. However, the rate of decay in blood flow following ischemia was significantly slower (p less than 0.05) for the COPD group (-0.036 ± 0.005 mL·100 mL-1·min-1·s-1) when compared to the control group (-0.048 ± 0.015 mL·100 mL-1·min-1·s-1). The results of this study suggest that the lower peak exercise capacity in patients with moderate COPD is not related to a loss in leg vasodilatory capacity. Study 4 examined the dynamics of oxygen uptake kinetics during high-intensity constant-load cycling performed at 70% of the peak power attained during an incremental exercise test in 7 patients with moderate COPD and 7 healthy age-matched controls. The time constant of the primary component (phase II) of oxygen uptake was significantly slower in the COPD patients (82 ± 8 s) when compared to healthy control subjects (44 ± 4 s). Moreover, the oxygen cost per unit increment in power output for the primary component and the overall response were significantly higher in patients with COPD than in healthy control subjects. A slow component was observed in 5 of the 7 patients with COPD (49 ± 11 mL·min-1), whereas all of the control subjects demonstrated a slow component of oxygen uptake (213 ± 35 mL·min-1). The slow component comprised a significantly greater proportion of the total oxygen uptake response in the healthy control group (18 ± 2%) than in the COPD group (10 ± 2%). In the COPD patients, the slow component amplitude was significantly correlated with the decrease in inspiratory capacity (r = -0.88, P less than 0.05; N=5), indicating that the magnitude of the slow component was larger in individuals who experienced a greater degree of dynamic hyperinflation. This study demonstrated that most patients with moderate COPD are able to exercise at intensities high enough to elicit a slow component of oxygen uptake during constant-load exercise. The significant correlation observed between the slow component amplitude and the degree of dynamic hyperinflation suggests that the work of breathing may contribute to the slow component in patients with COPD.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Physiotherapy and Exercise Science
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McVeigh, Beverley. « An acute care program for patients with chronic obstructive pulmonary disease ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ62030.pdf.

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Flaherty, Helen M. « Informal Caregivers’ Experience During Acute Exacerbation of COPD in Older Adults : A Dissertation ». eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsn_diss/51.

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Chronic obstructive pulmonary disease (COPD) has been recognized as a leading cause of mortality in older adults involving acute exacerbations as life-threatening events that lead to frequent hospitalization for care. Informal caregivers have been essential to helping older adults with COPD during an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A lack of empirical knowledge exists regarding the experience of informal caregivers of older adults with AECOPD in situation awareness for recognizing, understanding, and responding to an AECOPD in an emergent situation. This qualitative descriptive study explored situation awareness and its components of perception, comprehension and projection of next steps, including the caregiver’s confidence level during the AECOPD event. Fifteen informal caregivers, ages 31-77 years (mean age 48), who provided care for older adults with COPD were interviewed from an underserved community health center. The overarching theme derived from this study was something was wrong and something needed to be done. Subthemes emerged as a heightened sense of awareness, caregiver tipping point, planning next steps, caregiver confidence, and caregiver commitment. This study utilized situation awareness theory as a relevant guiding framework in exploring the experience of lay informal caregivers caring for older adults with AECOPD events. Study findings provided a description of the complex processes involved, including confidence level, for informal caregiver’s in situation awareness to recognize and respond to an AECOPD event in the older adult. Future targeted interventions need to address strategies to enhance individualized care for older adults with AECOPD events for managing care at home.

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Saudny-Unterberger, Helga. « Impact of nutritional support on changes in functional status during an acute exacerbation of chronic obstructive pulmonary disease (COPD) ». Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=23294.

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Despite the acknowledged importance of nutritional support for COPD patients, it is difficult to accomplish in acutely stressed individuals. A randomized trial of nutritional supplementation during an acute exacerbation was carried out in 16 hospitalized patients for a 2 week period. Six control patients consumed a standard diet supplying 1,951 $ pm$ 130 (mean $ pm$ SEM) kcal and 80 $ pm$ 6 g protein/d, while ten treatment patients, in addition to the usual diet received oral supplements (Ensure) or snacks, resulting in an intake of 2,516 $ pm$ 129 kcal (p = 0.012) and 99 $ pm$ 6 g protein/d (p = 0.059). Although the treatment subjects improved their intake over the control group, no significant improvement in nutritional status occurred in either group.
Forced vital capacity (FVC % predicted) improved significantly over the study period in treated vs control subjects (+11.10 $ pm$ 4.63 vs $-$4.50 $ pm$ 2.14; p = 0.026). Nitrogen balances were calculated for 9 subjects, and all were in negative balance ($-$8.42 $ pm$ 1.74 g nitrogen/d) with no difference between groups.
Because of the high doses of methylprednisolone administered (69.6 $ pm$ 8.3 mg/d), and their known catabolic effects, we examined whether the dose affected nitrogen balance and muscle strength. Both nitrogen balance (r = $-$0.73; p = 0.025) and grip strength (r = $-$0.76; p $<$ 0.001) worsened with higher doses of steroids. The catabolic process may have resulted from elevated energy requirements, inadequate intake of protein and energy or been induced by high doses of steroids.
Hospitalized COPD patients are highly stressed and catabolic, and the means to preventing protein wasting during an acute exacerbation of their disease remains to be established. (Abstract shortened by UMI.)

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Butt, Muhammad U. « AGGRESSIVE DIURESIS AND SEVERITY-ADJUSTED LENGTH OF HOSPITAL STAY IN ACUTE CONGESTIVE HEART FAILURE PATIENTS ». UKnowledge, 2018. https://uknowledge.uky.edu/crd_etds/2.

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To see if aggressive diuresis in first twenty four hours is associated with a comparable number of total days in the hospital as compared to non-aggressive diuresis. In this retrospective cohort study, we compared the length of hospital stay of consecutive patients admitted in one year based on their diuresis during the first twenty-four hours of hospitalization: aggressive diuresis (group 1) i.e. > 2400mL versus non-aggressive diuresis (group 2) i.e. ≤ 2400mL urine output. Patients were excluded if in cardiogenic shock, had creatinine level above 3 mg/dL on admission, or on dialysis. A total of 194 patients were enrolled (29 in group 1 and 165 in group 2 respectively). The Kaplan-Meier estimate of the median cumulative proportion of patients still hospitalized for the group 1 was 4 days and in group 2 was 5 days (log-rank test; P=0.67). In univariate analysis, Cox PH regression showed unadjusted hazard rate of discharge from hospital was slightly higher in group 1 than group 2 but was statistically non-significant (HR=1.08; P=0.70). In multivariate Cox model analysis, creatinine at the time of admission when greater than 1.6mg/dL (P=0.75), LVEF (P= 0.14), total twenty-four hours dose of intravenous Furosemide given (P=0.98) and interaction between Furosemide dose and Creatinine level (P=0.79) were not significant predictor of hospital discharge. Adjusted hazard rate for discharge from hospital was 12% higher in group 1 than group 2 but still statistically non-significant (HR=1.12; P=0.60). Since the length of hospital stay is similar between two groups, we suggest the goal of diuresis to be less than 2400mL in first twenty-four hours to prevent excessive dehydration.

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Jackson, Kim Geraldine. « Acute and chronic effects of monounsaturated fatty acid intake on chylomicron metabolism ». Thesis, University of Surrey, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360952.

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Rogers, Andrew Vincent. « Inflammatory cell distribution in human bronchial mucosa : influence of chronic and acute disease ». Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.440463.

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Gallagher, Sean. « Reducing acute kidney injury in patients with chronic kidney disease undergoing cardiac surgery ». Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8669.

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Patients with chronic kidney disease (CKD) are a group with a markedly increased risk of adverse events following cardiac surgery. A particular problem for these patients is the development of post-operative acute kidney injury (AKI), which is associated with a significant increase in morbidity and mortality. Currently, there are no effective therapies proven to modify AKI in patients undergoing cardiac surgery. This thesis has three parts. The first describes an analysis of the Barts Health NHS Trust cardiac surgical dataset. Specifically, outcomes of patients with CKD and AKI were examined. The second describes a randomized control trial that examined the effect of remote ischaemic preconditioning (RIPC) upon AKI and myocardial injury in patients with CKD undergoing coronary artery bypass graft surgery (CABG). The final part describes the development of a panel of AKI biomarkers to allow the accurate prediction of AKI in patients with CKD undergoing CABG. The aims of this thesis were: 1. In our local cardiac surgical cohort, a. To assess the effects of CKD upon outcomes after CABG. b. To asses the prognostic importance of AKI after CABG. 2. To assess the potential for RIPC to reduce AKI and myocardial injury in patients with CKD undergoing CABG. 3. To investigate the diagnostic performance of serum and urine AKI biomarkers in a population of patients with CKD undergoing CABG. Analysis of the Barts Health NHS Trust cardiac surgical dataset confirmed that patients with CKD account for almost one-third of patients undergoing CABG. However, these patients account for a disproportionate two-thirds of all early mortality. CKD was also independently associated with late mortality after CABG. AKI was common in these patients. AKI was associated with late mortality even after accounting for pre-operative comorbidity and surgical complexity. In the randomized control trial, RIPC showed no effect upon the incidence of AKI or myocardial injury in the. 86 patients with CKD recruited. Secondary analysis of serum and urine biomarkers collected found change in serum cystatin C and NGAL as impressive predictors of AKI in patients with CKD. They allowed accurate early prediction of AKI more than 24 hours before diagnosis was possible using serum creatinine.

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Fossati, S. « Acute cardiovascular effects of exposure to airborne particulate matter : a study of possible pathogenetic mechanisms ». Doctoral thesis, Università degli Studi di Milano, 2009. http://hdl.handle.net/2434/64549.

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Introduction Increased levels of particulate matter air pollution (PM) have been associated with increased cardiovascular morbidity and mortality, especially in elderly adults and in people suffering from cardiovascular or lung diseases. The mechanisms behind these effects are still unknown, although some hypothesis have been postulated that include a modification of autonomic regulation of heart rhythm and the induction of arrhythmic events. Which fraction of PM is the most harmful is still controversial, and few studies investigated the role of personal exposure to different fractions, and in particular ultrafine particles. *Aim The aim of this thesis is to assess: i) the association between the individual exposure to PM and the modification of HRV (an index of autonomic regulation of heart rhythm) and QTec (an index of a pro-arrhythmic status), both in healthy subjects and in subjects suffering from chronic ischemic heart disease or chronic lung disease; ii) the potential role of inflammation and baseline health status in these associations; iii) the role of different PM fractions in these associations. *Materials and methods 27 healthy individuals (“Healthy” group), 34 individuals with chronic ischemic heart disease (Heart group), 18 with chronic asthma or COPD (Lung group) underwent a 24-hour exposure/clinical evaluation protocol during their habitual activities, both in the warm season (Summer) and in the cold season (Winter). Individual exposure to UFPs, fine and coarse particles number concentration, gravimetric PM2.5 and PM10 was assessed for each subject, along with a 24-hour ambulatory ECG, for the assessment of heart rate variability and QT period. Mixed effects models were used to evaluate the associations between exposure to particles and clinical parameters, during 24-hour, day- and night-time. *Results The mean±SD age of the study population was 64±10 years and 65% were male. 24-hour individual exposure levels to UFPs, PM2.5 and PM10 (median (25th-75th) or mean±SD) were 19.643 (14.520-30.328) #/cm3, 41,53±22,52 µg/m3 and 51,97±24,31 µg/m3 respectively. Higher individual exposure was observed during day-time, except for particles in the accumulation mode (FP0,3-1). A -5,69% (95% C.I. -10,76 to -0,62) and -8,61% (-17,57 to 0,35) decrease in night-time SDNN (night-SDNN) in the total sample and in the Heart group respectively, was observed for an interquartile range (IQR) increase in FP0,3-1 during the night period (night-FP0,3-1). The same, even stronger, association was observed between day-FP0,3-1 and night-SDNN, and was confirmed in all groups. In subjects with higher levels of hsCRP, an increase in all night-time vagal indices (PNN50>HF>rMSSD) was observed in the totality of subjects for an IQR increase in day-FP2.5-10, and confirmed in healthy subjects only. In all subjects with lower levels of hsCRP, a +12,21% (95% C.I. 2,67 to 22,64) and +7,09 (0,12 to 14,55) increase in night-HF for an IQR increase in night-FP0,3-1 and in night-FP2,5-10 respectively was found, coupled to a decrease in the LF/HF ratio. These findings were confirmed in healthy subjects only. These associations were even stronger between day-FP and night-HRV in the total sample, and confirmed in the “Healthy” and the Heart groups. *Discussion and conclusion The observed results suggest a major role of fine particles leading to acute and delayed alteration in autonomic control of heart rhythm in healthy subjects and subjects with chronic ischemic heart disease, probably not related to the inflammatory status. On the other hand, coarse particles possibly need higher concentrations to exert their effects on autonomic control of heart rhythm, and these effects could be linked to inflammatory mechanisms in healthy subjects. Ultrafine particles appear to be less involved in the observed associations suggesting for these particles mechanisms other than those investigated in this study.

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Fisher, Kimberly A. « Impact of COPD on the Mortality and Treatment of Patients Hospitalized with Acute Decompensated Heart Failure (The Worcester Heart Failure Study) : A Masters Thesis ». eScholarship@UMMS, 2014. https://escholarship.umassmed.edu/gsbs_diss/717.

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Objective: Chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients with heart failure, yet little is known about the impact of this condition in patients with acute decompensated heart failure (ADHF), especially from a more generalizable, community-based perspective. The primary objective of this study was to describe the in-hospital and post discharge mortality and treatment of patients hospitalized with ADHF according to COPD status. Methods: The study population consisted of patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during 4 study years: 1995, 2000, 2002, and 2004. Results: Of the 9,748 patients hospitalized with ADHF during the years under study, 35.9% had a history of COPD. The average age of this population was 76.1 years, 43.9% were men, and 93.3% were white. At the time of hospital discharge, patients with COPD were less likely to have received evidence-based heart failure medications, including beta-blockers and ACE inhibitors/angiotensin receptor blockers, than patients without COPD. Multivariable adjusted in-hospital death rates were similar for patients with and without COPD. However, among patients who survived to hospital discharge, patients with COPD had a significantly higher risk of dying at 1 (adjusted RR 1.10; 95% CI 1.06, 1.14) and 5-years (adjusted RR 1.40; 95% CI 1.28, 1.42) after hospital discharge than patients who were not previously diagnosed with COPD. Conclusions: COPD is a common co-morbidity in patients hospitalized with ADHF and is associated with a worse long-term prognosis. Further research is required to understand the complex interactions of these diseases and to ensure that patients with ADHF and COPD receive optimal treatment modalities.

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Fisher, Kimberly A. « Impact of COPD on the Mortality and Treatment of Patients Hospitalized with Acute Decompensated Heart Failure (The Worcester Heart Failure Study) : A Masters Thesis ». eScholarship@UMMS, 2007. http://escholarship.umassmed.edu/gsbs_diss/717.

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Objective: Chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients with heart failure, yet little is known about the impact of this condition in patients with acute decompensated heart failure (ADHF), especially from a more generalizable, community-based perspective. The primary objective of this study was to describe the in-hospital and post discharge mortality and treatment of patients hospitalized with ADHF according to COPD status. Methods: The study population consisted of patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during 4 study years: 1995, 2000, 2002, and 2004. Results: Of the 9,748 patients hospitalized with ADHF during the years under study, 35.9% had a history of COPD. The average age of this population was 76.1 years, 43.9% were men, and 93.3% were white. At the time of hospital discharge, patients with COPD were less likely to have received evidence-based heart failure medications, including beta-blockers and ACE inhibitors/angiotensin receptor blockers, than patients without COPD. Multivariable adjusted in-hospital death rates were similar for patients with and without COPD. However, among patients who survived to hospital discharge, patients with COPD had a significantly higher risk of dying at 1 (adjusted RR 1.10; 95% CI 1.06, 1.14) and 5-years (adjusted RR 1.40; 95% CI 1.28, 1.42) after hospital discharge than patients who were not previously diagnosed with COPD. Conclusions: COPD is a common co-morbidity in patients hospitalized with ADHF and is associated with a worse long-term prognosis. Further research is required to understand the complex interactions of these diseases and to ensure that patients with ADHF and COPD receive optimal treatment modalities.

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Stell, Ian Michael. « Extending the role of noninvasive ventilation in acute exacerbations of chronic obstructive pulmonary disease ». Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406692.

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Fearn, Amy. « Role of the immune system during the development of acute and chronic renal disease ». Thesis, University of Newcastle Upon Tyne, 2013. http://hdl.handle.net/10443/1862.

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The purpose of this thesis was to investigate the contribution of the inflammatory mediators Nuclear factor κB and complement during the progression of renal diseases. The first two results chapters in this thesis demonstrated a novel role for complement component 3 (C3) during the progression of chronic renal disease in the murine model of unilateral ureteric obstruction (UUO) C3 gene up-regulation and complement activation persisted throughout the course of UUO in wild type (WT) mice. In situ hybridisation showed that renal tubular epithelial cells were the primary site of C3 gene expression during early ureteric obstruction in the renal cortices of WT mice. Gene expression for transforming growth factor-beta (TGF-β) and collagen I in obstructed C3 deficient (C3-/-) mouse kidneys was significantly reduced compared with obstructed kidneys from WT mice. The decrease in TGF-β and collagen I also coincided with a significant reduction in mRNA expression for alpha-smooth muscle actin (α-SMA) as well as a significant decrease in interstitial collagen deposition. In addition to these observations, the number of infiltrating CD8+ T cells and F4/80+ macrophages counted within the cortical tubulointerstitial compartment, was significantly higher in C3-/- mice. Gene expression for the membrane-bound complement regulatory proteins complement receptor-related protein-y (crry), CD59a and decay accelerating factor 1 (DAF1) decreased in WT and C3-/- mice during the course of UUO. In particular, crry, CD59a and DAF1 mRNA expression was found to be much lower in C3-/- mice. A transition from membrane to cytoplasmic expression of crry protein was also demonstrated in tubular epithelial cells of obstructed WT mouse kidneys. In contrast to this, factor H gene expression was markedly elevated in WT mice, but not in C3-/- mice. 13 In vitro stimulation of mouse proximal tubular cells using lipopolysaccharide (LPS) resulted in complement activation, C3 gene up-regulation and production of C3 protein, providing an in vitro model to use for future targeting of proximal tubular epithelial cell C3 gene expression. The final results chapter of this thesis demonstrated an important role for nuclear factor kappa-B (NF-κB) subunit nfκb1 during the progression of renal inflammation in the nephrotoxic serum nephritis model of acute renal injury. nfκb1 deficient mice developed significantly worse glomerular injury and proteinuria and displayed sustained up-regulation of interleukin-6 and S100 calcium binding proteins A8 and A9. Finally, in contrast to observations in the nephrotoxic serum model, fibrosis, immune cell infiltration and cytokine mRNA expression were all unchanged in nfκb1 deficient mice compared with WT mice after ten days of ureteric obstruction.

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Uniacke, Mark. « The natural history of acute kidney injury and its relationship to chronic kidney disease ». Thesis, University of Southampton, 2012. https://eprints.soton.ac.uk/361330/.

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Corten, Lieselotte. « The use of assisted autogenic drainage in children with acute and chronic respiratory disease ». Doctoral thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/25169.

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Background: Respiratory problems, both acute and chronic, remain an important cause of disease burden for children worldwide. Airway clearance techniques, as part of the management of these conditions, might influence the course of the disease thereby reducing this burden. Objective: This PhD thesis aimed to explore the epidemiology and management of children with acute respiratory diseases admitted to a paediatric hospital in Cape Town, South Africa; and to determine the usefulness and safety of assisted autogenic drainage in children with an acute (pneumonia) or chronic (cystic fibrosis) respiratory disease. In order to do this, several linked studies were undertaken including a retrospective folder review, two systematic reviews and two pragmatic randomised controlled trials.

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Rudomanova, Valeriia. « Unraveling the Secrets of Kidney Disease : Novel Molecular Mechanisms of Acute and Chronic Kidney Injury ». University of Cincinnati / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1623250686588821.

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Bailey, Patricia Hill. « Patients', family caregivers', and nurses' stories of acute exacerbation events of Chronic Obstructive Pulmonary Disease ». Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/21379.

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Loschi, Michael. « CD19SFv-CAR regulatory T-cell prevent acute graft versus host disease and improve chronic graft versus host disease ». Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC265.

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La greffe de cellules souches hématopoïétiques est une option curative pour de nombreuses maladies hématologiques malignes et bénignes. Cependant, son effet bénéfique est contrebalancé par le développement de la maladie du greffon contre l'hôte (GVHD) aiguë et chronique. Les options thérapeutiques permettant de réduire l'incidence et la gravité de la GVH reposent principalement sur des médicaments pan-immunosuppresseurs qui exposent le destinataire à des infections opportunistes et à une rechute de la maladie d'origine. Les immunothérapies à base de cellules T régulatrices (Treg) se sont révélées efficaces, mais sont limitées par les capacités de suppression variables entre les produits et le nombre de Treg. L’ingénierie des récepteur antigénique chimérique (CAR) donne maintenant la possibilité de rediriger les cellules T et d’augmenter leur fonction. Ici, nous avons testé le Treg CAR 4-1BB ciblant le CD19 humain (hCD19) pour supprimer la GVHD. Nous avons constaté que le CD19SFv-CAR Treg est spécifiquement activé via leur CAR. Cette hyperactivation confère des capacités métaboliques et suppressives plus élevées. Après l’activation du CAR, le CD19SFv-CAR Treg affiche des capacités de migration accrues vers l’intestin, principal organe cible de la GVHD. Les CD19SFv-CAR Treg préservent la réponse du greffon contre la leucémie (GvL) et présente une activité anti-tumorale. Dans un modele de cGVHD les CD19SFv-CAR Treg éliminent les cellules B du centre germinatif (cellules B de GC) et améliore la fonction pulmonaire des receveurs. Cette étude identifie les CAR-hCD19 Treg comme un moyen d’améliorer l’efficacité de l’immunothérapie par Treg en augmentant les capacités de suppression du Treg, leur migration et leur métabolisme sans modifier la réponse GvL du greffon
Allo-hematopoietic stem cell transplantation is a curative option for many malignant and benign hematologic disorders. However, its beneficial effect is counterbalanced by the development of acute and chronic graft versus host disease (GVHD). The therapeutic options to reduce GVHD incidence and severity mostly rely on pan immunosuppressive drugs that expose the recipient to opportunistic infections and relapse of the original disease. Regulatory T cell (Treg) therapies have proven efficient but are limited by inter product variable suppressive capacities and number of Treg. The chimeric antigen receptor (CAR) engineering now give the opportunity to redirect Tcell and increase their function. Here, we tested CAR 4-1BB Treg targeting the human CD19 (hCD19) to suppress GVHD. In aGVHD we found that CD19SFv-CAR Treg are specifically activated through their CAR. This hyperactivation confers higher metabolic and suppressive capacities. After CAR activation, CD19SFv-CAR Treg display increased homing abilities to the gut which is the main target organ in aGVHD. CD19SFv-CAR Treg preserve the Graft versus leukemia (GvL) response and display anti-tumor activity. In cGVHD CD19SFv-CAR Treg eliminate Germinal center B-cells (GC B-cells) and improve the pulmonary function of the recipients. This study identifies the CAR-hCD19 Treg as a way to improve Treg immunotherapy efficiency by increasing Treg suppressive capacities, homing, and metabolism without altering the GvL response of the graft

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Huiart, Laetitia. « Corticosteroid use and the risk of acute myocardial infarction in patients with chronic obstructive pulmonary disease ». Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=19420.

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Patients with chronic obstructive pulmonary disease (COPD) use medications known to have cardiovascular effects. Yet, the burden of cardiovascular disease in COPD and the effect of corticosteroids used in its treatment have not been described. We used the Saskatchewan health services database to form a population-based cohort of 5648 patients treated for COPD and followed during 1990-99. Cardiovascular morbidity and mortality were higher in our cohort than in the general population (Standardized Rate Ratio=l .9 and 2.0 respectively). Ischemic heart disease (19.6 per 1000 person-years) was a more frequent cause of death than COPD itself (15.5 per 1000 person-years). In a nested case-control analysis, doses of oral corticosteroids larger than 5 mg of prednisone per day increased the risk of AMI (Rate Ratio=l .81 ; 95%CI 1.05 -3.13). However, a réduction of the risk of AMI was observed with doses of inhaled corticosteroids ranging from 50 to 200 micrograms per day (Rate Ratio= 0.68; 95%CI 0.47 - 0.99). The burden of cardiovascular disease in COPD patients may be greater than that of the lung disease itself. The effects of corticosteroids on the cardiovascular system should be taken into account.

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Mirza, Mohd Tahir Beg Fatim Tahirah. « Optimising Assessment and Rehabilitation in People Hospitalised with an Acute Exacerbation of Chronic Obstructive Pulmonary Disease ». Thesis, Curtin University, 2016. http://hdl.handle.net/20.500.11937/76705.

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This research; (i) evaluated the measurement properties of the two-minute walk test (2MWT), including the effect of test repetition, coefficient of repeatability and validity, and compared the cardiorespiratory responses and symptoms reported during the 2MWT and the six-minute walk test, (ii) developed regression equations to estimate the two-minute walk distance and (iii) evaluated the effectiveness of an exercise program in people hospitalised with an AECOPD on exercise capacity, muscle force, functional performance and physical activity.

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Kadri, Amer N., Roop Kaw, Yasser Al-Khadra, Hasan Abumasha, Keyvan Ravakhah, Adrian V. Hernandez et Wai Hong Wilson Tang. « The role of B-type natriuretic peptide in diagnosing acute decompensated heart failure in chronic kidney disease patients ». Termedia Publishing House Ltd, 2018. http://hdl.handle.net/10757/624714.

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Introduction: Chronic kidney disease (CKD) and congestive heart failure (CHF) patients have higher serum B-type natriuretic peptide (BNP), which alters the test interpretation. We aim to define BNP cutoff levels to diagnose acute decompensated heart failure (ADHF) in CKD according to CHF subtype: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Material and methods: We reviewed 1,437 charts of consecutive patients who were admitted for dyspnea. We excluded patients with normal kidney function, without measured BNP, echocardiography, or history of CHF. BNP cutoff values to diagnose ADHF for CKD stages according to CHF subtype were obtained for the highest pair of sensitivity (Sn) and specificity (Sp). We calculated positive and negative likelihood ratios (LR+ and LR–, respectively), and diagnostic odds ratios (DOR), as well as the area under the receiver operating characteristic curves (AUC) for BNP. Results: We evaluated a cohort of 348 consecutive patients: 152 had ADHF, and 196 had stable CHF. In those with HFpEF with CKD stages 3–4, BNP < 155 pg/ml rules out ADHF (Sn90%, LR– = 0.26 and DOR = 5.75), and BNP > 670 pg/ml rules in ADHF (Sp90%, LR+ = 4 and DOR = 6), with an AUC = 0.79 (95% CI: 0.71–0.87). In contrast, in those with HFrEF with CKD stages 3–4, BNP < 412.5 pg/ml rules out ADHF (Sn90%, LR– = 0.19 and DOR = 9.37), and BNP > 1166.5 pg/ml rules in ADHF (Sp87%, LR+ = 3.9 and DOR = 6.97) with an AUC = 0.78 (95% CI: 0.69–0.86). All LRs and DOR were statistically significant. Conclusions: BNP cutoff values for the diagnosis of ADHF in HFrEF were higher than those in HFpEF across CKD stages 3–4, with moderate discriminatory diagnostic ability.
Revisión por pares

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Kirk, Richard James Thompson. « Endothelial function response to different modes of acute and chronic exercise in both health and diseased populations ». Thesis, University of Hull, 2014. http://hydra.hull.ac.uk/resources/hull:16454.

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Endothelial microparticles (EMP) offer an insight into the state of the endothelium and are known to be elevated in diseases characterised by endothelial dysfunction (ED) (Horstman et al., 2004; Vince et al., 2009a). EMP have also been shown to increase after exercise/endothelial stress in healthy individuals (Sossdorf et al., 2011; Vince et al, 2009) but this area remains relatively novel. The purpose of the first experiment was to quantify the effects of an acute bout of strenuous exercise on the circulating levels of EMP and to assess if this effect is different after the ingestion of an extensively researched ergogenic aid (sodium bicarbonate, NaHCO3). Seven physically active and apparently healthy males volunteered to perform 10 x 15 second (s) cycle sprints after the ingestion of either 0.03 g.kg.BW−1 NaHCO3 or 0.045 g.kg.BW−1 of a placebo (sodium chloride, NaCl) in capsules. The ingestion of NaHCO3 induced a pre exercise alkalosis as evidenced by a significantly altered resting acid base status, but had no influence on levels of EMP in healthy males. As a result, the data was combined for the two experimental groups, and the exercise produced a significantly increased level of CD105+ MP (MP; microparticles) at 90 minutes (min) and 180 min when compared with resting levels (p = 0.010, p = 0.043 respectively). The observed peak value at 90 min was also significantly greater compared to immediately post exercise (p = 0.019). CD106+ MP also increased significantly to 90 min from immediately post exercise (p = 0.020) and this was still greater at 180 min compared to post exercise (p = 0.015). It was concluded that exercise of this nature was sufficient to elicit ED, although the endothelium shows signs of endothelial repair within a matter of hours (hr). Also, it appears that pre exercise alkalosis has no effect on the attenuation of EMP quantity. Additional work was completed to verify the novel finding that CD105+ MP and CD106+ MP appear markers of endothelial function (EF), and to further examine the quantification of EMP, this time in healthy females. There was also an additional blood draw in order to assess where the maximum level of endothelial stress was occurring post exercise. In the second experiment, 10 healthy females completed the identical repeated sprints protocol as the first experiment, this time without the ingestion of NaHCO3. CD105+ MP were increased 90 min post exercise compared to immediately after exercise (p = 0.042). There was again a decline in both markers from 90 min to 180 min, although this was not significant. Furthermore, with the addition of a blood draw at 45 min post exercise, it was suggested that EMP levels appear to be rising between 45 min and 90 min post exercise, speculating this is the time point of greatest endothelial damage. Finally, shear stress was suggested as a key reason behind the increase in endothelial damage as a result of exercise, as indicated by significant changes in variables such as heart rate (HR) and systolic blood pressure (SBP). The third experiment employed a longer 90 min interval cycling protocol with the purpose of quantifying EF over a greater period of time, allowing investigation into whether the markers of EF were altered in the same way as the previous two experiments. It was also an aim to further assess the possible influence of shear stress factors on ED. Fourteen healthy males completed 90 min of high intensity aerobic exercise, and there were several changes in both CD105+ MP and CD106+ MP. CD105+ MP rose significantly from rest to an observed peak at 90 min (p = 0.019). Both of these markers indicated a significant restoration of the endothelium as indicated by a fall from peak values during recovery to 180 min post exercise (CD105+ MP, p = 0.009; CD106+ MP, p = 0.022). This experiment concluded that the endothelium is greatly affected by highly intense exercise over a prolonged period of time, but is recovered fully in a time period of 3 hr. The effects of shear stress again appear to be largely influential, but future work must now be conducted in order to build on the findings from this research and examine shear stress closely during exercise and its relationship with EMP quantification. It was the aim of the next experiment to investigate two separate methods of assessing EF (EMP and EndoPAT-2000), this time in a group of sedentary, but otherwise healthy individuals, in order to monitor the changes as a result of an acute bout of moderate intensity acute exercise. There were no significant differences found in EF as a result of exercise. This was indicated by no significant changes in CD105+ MP concentrations from pre to post exercise (p = 0.84) or pre to 60 min post exercise (p = 0.612). CD106+ MP concentrations showed a decrease from resting values (2513 CD106+ MP per μl platelet free plasma; PFP) to immediately post exercise (1368 CD106+ MP per μl PFP, p = 0.09), and again at 60 min post exercise (1293 CD106+ MP per μl PFP, p = 0.073) compared to resting values. Additionally, EndoPAT scores were unaffected by exercise, with values of reactive hyperaemia index (RHI) changing from rest (2.43) to post exercise (2.57), but this was not significant (p = 0.35). Correlations were carried out in order to determine and comparisons that may have existed between EMP and EndoPAT score using RHI. Although there was a slight trend for the higher numbers of CD105+ MP to correlate with the lower scores of RHI (r = 0.327) this was not significant (p = 0.171). CD106+ MP showed no correlations with RHI (r = -0.087, p = 0.717). This chapter suggested that exercise was not strenuous enough to see any significant changes in EF, and EMP continue to appear efficient markers of EF in a population of sedentary, healthy individuals. The final experimental chapter investigated the effects of a supervised 8 week moderate intensity exercise programme on women with polycystic ovary syndrome (PCOS) and control women free from any known disease. The aim was to assess if this type of exercise could improve EF in this population, and if there was a relationship with EMP (CD105+ MP and CD106+ MP) to other factors, such as body composition and cardiorespiratory fitness. EF was improved from baseline values to post exercise programme, with CD105+ MP concentrations reducing from 2113 CD105+ MP per μl PFP to 424 CD105+ MP per μl PFP (p = 0.025). Furthermore, control women showed no significant change from pre to post exercise programme in CD105+ MP (p = 0.25), or CD106+ MP (p = 0.99). Further analysis was performed to look for any associations with the changes in EMP compared to body composition changes as a result of exercise, but no significant correlations existed. This study concluded that supervised, moderate intensity exercise independent of substantial weight loss was enough to elicit an00 improvement in EF in women with PCOS compared to healthy control women. Additionally, EMP concentrations appear to be able to effectively map changes in EF across a long period of time in diseased states, adding to the notion that EMP may account for EF. Future work must now build on these findings from this research and examine this response in a larger cohort involving PCOS women with varied phenotypes and body composition.

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Moga, Ana Maria. « Acute effect of noninvasive ventilatory support on maxium exercise capacity in patients with chronic obstructive pulmonary disease ». Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104757.

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Background: Non-invasive ventilation (NIVS) has been used as an adjunct to exercise. However, the extent to which NIVS improves exercise tolerance is highly variable. To date, no studies have examined the effect of NIVS on maximal exercise capacity when applied during a single exercise test. Objective: To evaluate the acute effect of BiPAP (Vision, Respironics), compared to no assist, on maximum exercise capacity in individuals with COPD. Methods: A randomized crossover design was used. Ten stable COPD patients (FEV1 53 ± % pred) performed three symptom-limited incremental exercise tests on a cycle ergometer while breathing through a mouthpiece, with either: i) without pressure support PS (ØPS), ii) PS of 0 cm H2O (PS0; IPAP & EPAP 4 cm H2O), or iii) 10 cm H2O (PS10; IPAP 14 & EPAP 4 cm H2O) of assist on separate days. Exercise workload (WLmax), dyspnea and leg effort (Borg), end-expiratory lung volume (EELV), breathing pattern, O2 uptake (VO2) and CO2 production (VCO2) were measured during exercise. Results: There was no difference in WLmax between PS10 (33±16) and PS0 (30.5±13). However, WLmax was lower with PS0 and PS10 than ØPS. Dyspnea at peak exercise was similar without PS, PS0 and PS10; at isoload it was lower without PS compared to PS10 and PS0 (p < 0.01). Leg effort at peak exercise was higher without PS than PS10 and PS0 (p < 0.05), whereas it was not different at isoload. Tidal volume (VT) and minute ventilation (VE) were highest with PS10 and lowest without PS both at peak exercise (p < 0.001) and isoload (p < 0.001). EELV was similar at peak exercise with all three conditions. VO2 and VCO2 were greater with PS10 and PS0 than without PS (both p < 0.001), both at peak exercise and isoload.Conclusion: Use of BiPAP during incremental exercise increases VT and VE at the expense of increasing the VO2, VCO2 and dyspnea, which in turns reduces WLmax in COPD patients.
Contexte : La ventilation non invasive (VNI) a été utilisée pendant un test d'exercice. Toutefois, la mesure dans laquelle la VNI améliore la tolérance à l'exercice est très variable. À ce jour, aucune étude n'a examiné l'effet de la VNI sur la capacité d'effort maximale lorsqu'il est appliqué au cours d'un test d'exercice dynamique aérobie maximal. Objectif: Evaluer l'effet aigu de BiPAP (Respironics), comparativement à l'absence d'aide, sur la capacité maximale d'exercice chez les individus atteints de la maladie pulmonaire obstructive chronique (MPOC). Méthodes: Une étude croisée randomisée a été utilisée. Dix patients souffrant de MPCO stable (VEMS1 53 ± % pred.) ont effectué trois preuves d'effort supplémentaire sur une bicyclette ergométrique tout en respirant à travers une bout buccal, soit) sans le soutien de la pression(ØPS), ii) avec un soutien de 0cm H2O (PS0; IPAP & EPAP 4 cm H2O) ou iii), avec un soutien de 10cm H2O (PS10; IPAP 14 & EPAP 4 cm H2O). La fin des tests a été déterminée par les symptômes des patients, et chacun des tests a été effectué pendant un jour différent. Pendant l'exercice, nous avons mesuré la charge de travail(WLmax), la dyspnée et l'effort de la jambe (Borg), le volume pulmonaire en fin d'expiration (EELV), rythme respiratoire, la consommation d'O2 (VO2) et la production de CO2 (VCO2). Résultats: Il n'y avait aucune différence dans la charge de travail maximale du pic entre PS 10(33 ±16) et PS0 (30,5 ±13). Toutefois, la charge de travail maximum du pic était plus faible avec PS0 et PS10 de ØPS. La dyspnée pendant le pic de l'effort a été similaire à ØPS, PS0 et PS10. À isoload, elle était inférieure à ØPS par rapport à PS10 et PS0 (p < 0,01). L'effort de la jambe à l'exercice de pointe était plus élevé à ØPS de PS10 et PS0 (p < 0,05), alors qu'il n'était pas différent au isoload. Le volume courant (VT) et la ventilation minute (VE) étaient les plus élevés avec PS10 et les plus bas à ØPS, à la fois à l'exercice de pointe (p < 0,001) et isoload (p < 0,001). EELV était similaire à l'exercice de pointe avec les trois conditions. VO2 et VCO2 ont été plus grande avec PS10 et PS0 de ØPS (les deux p < 0,001), à la fois à l'exercice de pointe et isoload.Conclusion: L'utilisation du BiPAP pendant l'exercice augmente VT et VE, ce qui cause une augmentation du VO2, VCO2, et la dyspnée, qui à son tour réduit WL à l'exercice maximal chez les patients MPOC.

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Van, der Schyff Nasief. « Risk factors for prolonged ventilation in patients with chronic obstructive pulmonary disease presenting with acute respiratory failure ». Master's thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/12112.

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Includes abstract.
Includes bibliographical references (leaves 35-37).
Patients with COPD presenting to the Emergency Unit with acute hypercapnic respiratory failure often require invasive mechanical ventilation and subsequent admission to the intensive care unit (ICU). These patients are at an increased risk of prolonged and complicated ventilation and often experience weaning difficulties. In addition, the impact of a previous episode of pulmonary tuberculosis that might have resulted in structural lung disease on the duration of mechanical ventilation in such patients has not previously been evaluated. Methods: All patients with COPD admitted to the Respiratory ICU at Tygerberg academic hospital from the 01st January 2004 until 31st December 2007 requiring intubation and invasive mechanical ventilation for acute hypercapnic respiratory failure were included in the study.

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Centi, Justin. « Autonomic dysfunction in Parkinson's Disease : an evaluation of acute and chronic effects of cognition and daily life ». Thesis, Boston University, 2013. https://hdl.handle.net/2144/12729.

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Thesis (Ph.D.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
Non-motor symptoms of Parkinson's disease (PD) have emerged as an important research topic. Autonomic dysfunction is particularly prevalent, with the most common manifestation being orthostatic hypotension (OH). While cognitive deficits have been demonstrated in PD even in the absence of dementia, there has been no investigation of the potential effects of hemodynamic disorders on cognitive performance. The main hypothesis of the present study was that PD patients with OH would be cognitively impaired relative to those without OH, especially when in the upright position. The effects of impaired postural hemodynamics on cognition were examined in 36 nondemented PD patients - 18 diagnosed with OH (PDOH) and 18 without OH (PDNOH) - and 18 healthy normotensive control participants (NC) matched for age, male:female distribution, and education. Neuropsychological measures of executive function, visuospatial performance, memory, and attention/concentration were repeated in supine and upright positions to evaluate chronic and acute hemodynamic effects, respectively. Autonomic measures, taken concurrent to neuropsychological testing, included beat-to-beat arterial pressure, electrocardiography, transcranial Doppler sonography, and respiratory function. The first study assessed cognition associated with a diagnosis of OH. The second examined the relation between changes in blood pressure and cerebral blood flow and the impact of impaired hemodynamics on cognition. The third assessed the relation between subjective autonomic complaints and measurable impairments in autonomies and cognition. As hypothesized, both PDNOH and PDOH were impaired relative to NC, regardless of posture. There were few chronic effects of OH on cognition (PDNOH vs. PDOH, supine) whereas PDOH were significantly more impaired than PDNOH when upright (acute effect). Cerebral blood flow was reduced in PDOH compared to PDNOH and NC, and this reduction was correlated with performance on cognitive tests. PDOH had more subjective autonomic and functional complaints than PD alone. The presentation of PD with comorbid OH is associated with cognitive impairment, particularly while in the upright position, in patients without dementia. The prevalence of comorbidity of OH in PD is significant. The accompanying cognitive deficiency indicates that OH should be treated as both a physiologically dangerous and neuropsychologically relevant issue in individuals with this disorder.

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Olesin, Elizabeth A. « Transcriptional Regulation of Effector and Memory Responses during Acute and Chronic Lymphocytic Choriomeningitis Virus (LCMV) Infection ». eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/1000.

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Transcriptional regulation of CD8+ T cell differentiation during acute and chronic viral infections is an intricate web made up of many of transcription factors. While several transcription factors have been elucidated in this process, there are still many more that remain elusive. In this work, we look into the role of two transcription factors, IRF4 and Runx2, and their role in CD8+ T cell terminal effector cells and memory precursor cells during acute LCMV-Armstrong infection. We found that IRF4 expression was regulated by TCR signal strength during infection, and that IRF4 expression levels directly correlated with the magnitude of the effector cell response. IRF4 was also shown to regulate T-bet and Eomes, two transcription factors critical for CD8+ T cell differentiation into effector and memory cells. From these results, we were interested in the potential role of IRF4 during chronic LCMV-clone 13 infection, where ratios of T-bet and Eomes are critical for viral clearance. We found that haplodeficiency of IRF4 in the T cell compartment lead to an increase in the ratio of Eomes to T-bet in T cells, which in turn affected the proportion of Eomeshi versus T-bethi cells and resulted in a loss in ability to clear viral infection. Irf4+/-Eomes+/- compound heterozygous mice were generated to test if decreasing Eomes expression would rescue the Irf4+/- phenotype. Irf4+/-Eomes+/- mice were phenotypically similar to WT mice in terms of Eomes to T-bet ratios, and were able to clear viral infection, demonstrating a critical role of IRF4 in regulating T-bet and Eomes during chronic viral infection. Next we looked into the role of Runx2 during acute LCMV-Armstrong infection and found that Runx2-deficient pathogen-specific CD8+ T cells had a defect in the total number of memory precursor cells compared to WT controls. We further showed that Runx2 was inversely correlated with TCR signal strength, and that Runx2 expression was repressed by IRF4. From these work, we have introduced two more transcription factors that are critical for CD8+ T cells differentiation during acute and chronic viral infection. Given the sheer number of transcription factors known to regulate these processes, having a full understanding of the transcriptional network will allow us to find the best targets for therapeutic intervention for treatments ranging from vaccine development and autoimmunity to cancer immunotherapy and treatment of chronic viral infections.

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Hindricks, Janka. « Serum levels of fibroblast growth factor-21 are increased in chronic and acute renal dysfunction ». Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-182270.

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The progressively increasing prevalence of the Metabolic Syndrome (MetS) has emerged as a major global health concern since the MetS is associated with an increased risk for cardiovascular morbidity and mortality. Central obesity represents a key feature of the MetS and is strongly related to all MetS comorbidities. Dysregulation of adipose tissue-derived proteins, so called adipokines, has been implied to partially contribute to these effects. Recently, fibroblast growth factor-21 (FGF-21) has been introduced as a novel insulin sensitizing and weight reducing adipokine with potential therapeutic properties. However, data on FGF-21 elimination are rather limited. Therefore, FGF-21 regulation in relation to renal function has been investigated in a patient population with chronic kidney disease (CKD, study population 1), as well as one with acute kidney impairment (study population 2). In study population 1 (n = 499), patients were distributed into five CKD subgroups according to estimated glomerular filtration rate (eGFR). Median FGF-21 serum concentrations progressively increased from CKD stage 1 to stage 5 and highest values of FGF-21 were detected in stage 5 (1: 86.4 ng/l; 2: 206.4 ng/l; 3: 289.8 ng/l; 4: 591.3 ng/l; 5: 1918.1 ng/l). Furthermore, eGFR remained the strongest predictor for FGF-21 levels in multivariate analysis. For study population 2 (n = 32), blood samples were obtained before elective unilateral partial or total nephrectomy, as well as within 30 hours after surgery. In this population FGF-21 levels significantly increased after surgery (325.0 ng/l) as compared to before surgery (255.5 ng/l). Furthermore, relative changes of FGF-21 were independently and positively predicted by relative changes of creatinine in this cohort. These results are in accordance with the hypothesis that FGF-21 is eliminated by the kidneys and that the extent of kidney dysfunction substantially contributes to serum FGF-21 levels. However, additional animal experiments and prospective clinical studies are needed to further elucidate the role of the kidneys in FGF-21 physiology.

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de, la Puente Robles Beatriz. « Role of the sigma-1 receptor in the sensory-discriminative and affective-motivational components of acute and chronic pain ». Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/360581.

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The present Doctoral Thesis focuses on the study of the sigma-1 receptor (σ1R) in the field of pain. This research has been a part of the preclinical σ1R project focusing on drug discovery of σ1R ligands for the treatment of pain at the pharmaceutical company ESTEVE. The overall purpose of this Doctoral Thesis was to explore the role of σ1R in the sensory-discriminative and affective-motivational components of pain. To this end, acetic acid-induced visceral pain and partial sciatic nerve ligation in mice were used to model an acute and chronic pain state, respectively. The sensory discriminative and affective-motivational components of pain in these models were infered by changes in reflexive and non-reflexive behavioural outcomes, respectively. Abdominal contractions (writhing) and paw behavioural hypersensitivity to mechanical and thermal stimuli were analysed as reflexive outcomes. On the other hand, pain-related changes of sweet preference, locomotor activity and reward-seeking behaviour were analysed as non reflexive outcomes. These models and behavioural outcomes were used to evaluate the effect of pharmacological and genetic blockade of σ1R and also the effects of some reference compounds. Furthermore, electrophysiological and molecular studies in knock-out (σ1R /-) mice were used to understand the role of σ1R in the sensory discriminative component of chronic pain. Taken together, the results of this Doctoral Thesis provide new knowledge about σ1R and support the clinical development of selective σ1R antagonists as a suitable therapeutic intervention to treat neuropathic pain and its mood-related comorbidities.
El dolor es una experiencia sensorial y emocional desagradable. Es un mecanismo muy complejo determinado por dos componentes: el componente sensorial discriminativo, que corresponde a los mecanismos neurofisiológicos de la nocicepción y que informa de las características del dolor (naturaleza, duración, intensidad,…) y el componente afectivo-motivacional, que expresa la connotación desagradable relacionada con la percepción del dolor y que conlleva consecuencias emocionales que afectan al estado de ánimo y al bienestar del individuo. En la presente Tesis Doctoral se estudian estos dos componentes que conforman el dolor, evaluando respuestas de comportamiento en dos modelos animales de dolor, un modelo de dolor agudo visceral y un modelo de dolor crónico de origen neuropático. Además, se estudia el papel del receptor sigma-1 (σ1R) en cada modelo animal de dolor, evaluando su posible implicación tanto en el componente sensorial como en el afectivo. Para ello, se pusieron en práctica dos estrategias experimentales. Por un lado, se utilizaron ratones modificados genéticamente a los que se les ha eliminado el gen del receptor del sigma-1 (ratones knock-out σ1R) y por otro lado, se realizó un tratamiento farmacológico sistémico en ratones salvajes (wild-type) con el E-52862 (S1RA), un antagonista del receptor sigma-1 altamente selectivo. El E-52862 es un compuesto que ha sido desarrollado por ESTEVE y que tras su primera evaluación en seres humanos ha demostrado un buen perfil de seguridad y tolerabilidad (estudios clínicos de Fase I). Actualmente continúa siendo evaluado en subsecuentes estudios clínicos como indicación para el dolor neuropático de diferentes etiologías (estudios de Fase II). Los resultados de esta Tesis Doctoral proporcionan nuevos conocimientos sobre el receptor sigma-1 que apoyan el desarrollo clínico del antagonista selectivo para este receptor, el E-52862, como una opción terapéutica adecuada para el tratamiento del dolor neuropático y las comorbilidades afectivas asociadas a esta patología.

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Björklund, Fredrik. « Platelet reactivity and comorbidities in acute coronary syndrome ». Doctoral thesis, Umeå universitet, Institutionen för folkhälsa och klinisk medicin, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-51096.

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Background In the event of an acute coronary syndrome (ACS), the risk of death and complications such as stroke and re-infarction is high during the first month. Diabetes, impaired kidney function, elevated markers of systemic inflammation and high level of platelet reactivity have all been associated with worsened prognosis in ACS patients. Impaired kidney function is a condition with high cardiovascular morbidity and there is an established association between level of kidney function and outcome in the event of an ACS. Aims We sought to investigate the level of platelet reactivity during the first days of an ACS and specifically the level of platelet reactivity in patients with different conditions associated with worsened prognosis in the event of an ACS. We also wanted to investigate the prognostic impact of baseline levels of cystatin C as well as the importance of decreasing kidney function during the first days of an ACS. Methods We included 1028 unselected patients with ACS or suspected ACS during the years 2002 and 2003, of which 534 were diagnosed with an acute myocardial infarction (AMI). Blood samples for measuring platelet aggregation, cystatin C levels and other clinically important biomarkers were collected day 1, 2, 3 and 5 following admission. Platelet reactivity was measured using 2 different methods. Platelet aggregation was measured using Pa-200, a particle count method, based on scattering of laser light. PFA 100 is a method of measuring primary hemostasis in whole blood. Results Platelet aggregation and comorbidities. We found an increase in platelet aggregation when an ACS was complicated by an infection and there was an increased frequency of aspirin non-responsiveness in patients suffering from pneumonia during the first days of an ACS. Furthermore, we found an independent association between levels of C-reactive protein and platelet aggregation. During the first 3 days following an acute myocardial infarction, platelet aggregation increased despite treatment with anti-platelet agents. Platelet aggregation was found to be more pronounced in patients with diabetes. Patients with impaired kidney function, showed increased platelet aggregation compared to patients with normal renal function, however, this difference was explained by older age, higher prevalence of DM and levels of inflammatory biomarkers. We found no independent association between chronic kidney disease (CKD) and levels of platelet aggregation. Kidney function and outcome Serum levels of cystatin C on admission had an independent association with outcome following an acute myocardial infarction. With a mean follow-up time of 2.9 years, the adjusted HR for death was 1.62 (95% CI 1.28-2.03; p<0.001) for each unit of increase in cystatin C on admission. The level of dynamic changes in cystatin C during admission for an acute myocardial infarction was independently associated with prognosis in patients with normal or mild impairment of renal function. The adjusted HR for death was 10.1 (95% CI 3.4-29.9; p<0.001). Conclusion In patients suffering from an AMI platelet aggregation increases during the first days, despite anti-platelet treatment. Diabetes, age and biomarkers of inflammation are independently associated with platelet aggregation. Admission levels of cystatin C as well as changes in cystatin C levels during hospitalisation are independently associated with outcome.

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Tsai, Ling Ling. « Novel Technologies to Measure Physical Activity and Improve Health Outcomes in People with Chronic Obstructive Pulmonary Disease ». Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/19974.

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Chronic obstructive pulmonary disease (COPD) is a common disease characterised by airflow limitation. In people with COPD, objectively measured physical activity is the strongest predictor of all-cause mortality. The effect of hospitalisation for an acute exacerbation of COPD (AECOPD) on physical activity levels is not well studied. Chapter 2 was a prospective observational study which determined the physical activity level of people hospitalised with an AECOPD (T1) and whether physical activity changed immediately after discharge (T2) and six weeks post hospital admission (T3). Physical activity levels were monitored using the SenseWear Armband and results showed a significant linear increase in steps per day from T1 to T3 (T1, mean (SD) 1385 (1972) steps/day; T2, 2040 (2680); T3, 2328 (2745), p=0.001). Pulmonary rehabilitation (PR) is an effective non-pharmacological intervention for people with stable COPD that increases exercise capacity but access to PR is poor in Australia. Alternative ways to deliver PR need to be developed and real-time videoconferencing technology offers a way to supervise exercise training in the home environment. The study in Chapter 3 determined the effect of supervised, home-based, real-time videoconferencing telerehabilitation on exercise capacity in people with stable COPD compared to usual care without exercise training. People randomised to the telerehabilitation group (TG) received exercise training three times a week for eight weeks. Results showed a significant increase in endurance shuttle walk test time in the TG compared to usual care (mean difference = 340s (95%CI: 153-526, p<0.001). Chapter 4 determined the level of satisfaction and experience in the people who completed the telerehabilitation program in Chapter 3. Results showed a high level of satisfaction with the quality of exercise sessions delivered via real-time videoconferencing technology.

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Dye, Andrew. « The role of Chlamydophila pneumoniae and 60KDa heat shock protein (HSP60) antibodies in acute and chronic respiratory disease ». Thesis, University of Sheffield, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408823.

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Steer, Alan John. « Survival, quality of life and health resource use following hospitalisation for acute exacerbations of chronic obstructive pulmonary disease ». Thesis, University of Newcastle upon Tyne, 2013. http://hdl.handle.net/10443/2036.

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Background Hospital admissions with acute exacerbations of chronic obstructive pulmonary disease are common and associated with high mortality rates, frequent readmission and worse quality of life. An ability to identify patients at risk of subsequent poor outcome is lacking and the longitudinal change in quality of life following discharge is uncertain. Methods The study consisted of two parts: 1) Clinical data were collected on 920 consecutive patients hospitalised with exacerbations. The ability of a novel modification of the traditional MRC dyspnoea scale (the extended MRC dyspnoea scale, eMRCD) to identify patients at risk of poor outcome was assessed. Independent predictors of important clinical outcomes were recorded and clinical prediction tools derived. 2) A subgroup of 183 patients underwent longitudinal assessment of quality of life following hospital discharge and predictors of quality of life decline were identified. Results The study population was similar to that reported in UK national audits. 96 (10.4%) patients died in-hospital and 37.3% were readmitted to hospital, or died without being readmitted, within 90-days of discharge. The eMRCD was a better predictor of outcome than the traditional scale and, compared to all clinical variables, was the single strongest predictor of mortality and readmission Strong independent predictors of many important clinical outcomes were identified and, notably, the DECAF (dyspnoea, eosinopenia, consolidation, acidaemia, atrial fibrillation) predictive tool was derived and shown to be an excellent, and internally valid, mortality predictor (area under ROC curve = 0.858). Most patients who survived to discharge reported an improvement in respiratory symptoms and quality of life during follow-up. We defined a subgroup of patients who experienced poor post-discharge quality of life and identified robust, simple-to- measure predictors of poor quality of life. Conclusions Important patient outcomes can be accurately predicted in this population. Application of our results may reduce morbidity and mortality in this common and frequently fatal condition by improving clinical decision making regarding appropriate level of care, location of care and resource allocation.

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Bourne, Simon Charles. « The effect of smoking on the severity, and mechanisms of acute exacerbations of chronic obstructive pulmonary disease (COPD) ». Thesis, University of Southampton, 2008. https://eprints.soton.ac.uk/67617/.

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COPD (Chronic Obstructive Pulmonary Disease) worldwide has a prevalence of 10% in men and 8.5% in women. Exacerbations of COPD account for approximately 10% of all acute medical admissions. Projected prevalence figures suggest that by 2020 COPD will be the third leading cause of mortality worldwide thus imposing a significant burden on healthcare resources in the future. Acute exacerbations are not only responsible for a decline in the patient’s quality of life, but have a major socioeconomic impact. Following a pilot study that showed current smokers recover lung function much more slowly from their exacerbation than ex smokers, I initiated a properly powered prospective study to investigate the difference between the two groups. A total of 58 patients admitted with acute infectious exacerbations of COPD were recruited to the study to determine the effect of smoking status on their exacerbation. Throughout the admission lung function was measured. Sputum was cultured for bacteria, and PCR used to detect viral infection. Blood and sputum cells were analyzed by flow cytometry. Serum was collected for CRP levels. Ex-smokers recovered significantly more quickly than current smokers in all spirometric parameters (P<0.01), and were discharged sooner (mean 3.08 vs 5.59 days, P<0.001). Sputum culture was positive for more pathogenic bacteria in current smokers, especially H. influenzae, which was associated with a significantly higher CRP rise (p<0.05) than any other organism. CD8+ T cells predominated in the sputum of ex-smokers while CD4+ T cells were the dominant cell type in current smokers (p<0.01). Current smoking is a risk factor for more severe exacerbations, delayed recovery and prolonged hospitalization. This may result from a variety of factors including bacterial, immune mediated responses and systemic inflammation.

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Allahwala, Usaid. « Anatomical, haemodynamic, biochemical and imaging characteristics of the coronary collateral circulation in acute and chronic atherosclerotic disease processes ». Thesis, The University of Sydney, 2020. https://hdl.handle.net/2123/25095.

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Aim: Although frequently identified during coronary angiography, the mechanisms by which coronary collaterals develop, and their prognostic implications are, to date, unknown. This body of work aims to determine the prevalence and predictors of coronary collateral recruitment in the setting of ST elevation myocardial infarction (STEMI) and chronic total occlusion (CTO) and to determine their prognostic impact. Furthermore, to identify biochemical, cellular and haemodynamic processes by which collaterals are recruited and mature, and influence haemodynamics in the coronary circulation. Methods: Anatomical grading of collaterals using the Rentrop classification was performed in a large cohorts of patients with STEMI and CTO to determine predictors, reproducibility and prognostic implications of collaterals. Data linkage with other health parameters including a history of obstructive sleep apnoea (OSA) and prior coronary artery bypass grafting (CABG) was performed to determine impact of comorbidities and haemodynamic modulation on collateral recruitment. Subsequent systematic reviews and meta-analyses were performed. Invasive haemodynamic assessment of coronary blood flow and pressure in the presence and absence of collaterals was correlated with endothelial, haematological, biochemical and proteomic markers in both human and animal studies. Results: The important and novel findings are; - The presence of acutely recruited robust collaterals in the setting of STEMI are associated with a reduction in mortality and improved left ventricular function. - In the setting of a CTO, robust collaterals do not reduce mortality or risk of future ischaemic events, but do increase likelihood of successful percutaneous revascularisation. - Collateral maturation is driven by an elevation in shear stress, alterations in blood flow and tissue ischaemia. - The presence of collaterals results in a consistent increase in coronary blood flow in the donor vessel, with resultant effect on both pressure and flow derived indices of ischaemia assessment commonly used in clinical practice. - Recruitment and maturation of coronary collaterals are associated with upregulation of endothelial derived chemoattractant proteins, growth factors and transcription factors. - Coronary artery bypass grafting to a donor vessel, results in poorer collateral recruitment, likely driven by alterations in coronary blood flow and endothelial shear stress - The presence of OSA is associated with more robust coronary collaterals in both the setting of STEMI and CTO, however in more severe forms of OSA, characterised by severe and prolonged hypoxia, collateral recruitment is attenuated. Conclusions: Coronary collaterals impart significant prognostic implications in the setting of acute and chronic coronary artery disease, recruited as a result of alterations in coronary haemodynamics and tissue ischaemia with resultant downstream activation of growth factors, chemokines and transcription factors. Ongoing research is necessary to determine whether this prognostic advantage can be translated into meaningful therapeutic targets along with a greater understanding of clinical implications of collaterals.

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Armitage, Trudi. « Development of improved diagnostics for acute and persistent Chlamydia trachomatis infections ». Queensland University of Technology, 2007. http://eprints.qut.edu.au/16584/.

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The asymptomatic nature of chlamydial infection renders the differential diagnosis of acute and chronic infection difficult. An untreated Chlamydia trachomatis infection can become chronic, result in disease sequelae such as salpingitis and pelvic inflammatory disease (PID), and ultimately culminate in tubal occlusion and infertility. Diagnostic tests for C. trachomatis such as nucleic acid amplification testing (PCR), antigen detection and serological methods have variable performance capabilities with respect to sensitivity, specificity and stage of infection. The use of PCR as a diagnostic tool is somewhat limited, as specimen collection is routinely sampled from the lower genital tract; hence, infections in the fallopian tube where inflammatory damage is most significant, escape detection. Furthermore, PCR can only detect selected Chlamydia DNA sequences from readily accessible sites of the genital tract, and therefore cannot differentiate between acute and chronic infection. Other serological assays aim to discriminate the various stages of C. trachomatis infection through identification of key antigens. The efficacy of these assays however is impeded due to cross-reactivity between chlamydial species and the subsequent antibody response against the target antigen is not restricted to patients with a specific stage of infection. To identify antibody responses capable of differentiating various states of chlamydial infection, samples were collected from both men and women given the variability of immune responses between the two genders. Samples were assigned to a patient group according to infection status and then probed against protein extracts of HEp-2 cells infected with C. trachomatis serovar L2 and HEp-2 cells pre-treated with IFN-γ and infected with C. trachomatis serovar L2. (persistence cell culture) Serological analysis revealed the presence of five antigens (denoted bands A, B, C, D and M) which were shown to be differential between patient groups. Identification of bands B and C by N-terminal sequencing provided two possible candidates for each antigen, ie. CT727 and CT396 (band B) and CT157 and CT423 (band C). In contrast, band M which was unique to males was a PmpB (probable outer membrane protein B) fragment. The four target antigens (CT157, CT423, CT727 and CT396) were expressed as recombinant proteins using autoinduction media and were subsequently probed by both male and female sera to evaluate their diagnostic potential. Results showed that two chlamydial antigenic targets (CT157 and CT727) have the potential to discriminate between acute and chronic C. trachomatis infection. However, since only a small number of samples (n = 3) were used for this aspect of the study, the findings should simply be viewed as preliminary. In females, sensitivity and specificity values were derived using various combinations of the four target antigens into a panel format for the purpose of detecting chronic C. trachomatis infections. The preferred format was B + C with a sensitivity and specificity of 80% and 84% respectively. Using the IFN-γ-mediated persistence model, only two of the five antigenic targets were shown to be differentially expressed. PmpB in males and CT157 (the most likely band C candidate) in females were shown to be up-regulated to varying degrees in samples across the patient groups. We also demonstrated that no other chlamydial antigens are up-regulated during a persistent C. trachomatis infection. In conclusion, although combinations of bands A, B, C, D and M differentiate between male and female patient groups under normal chlamydial growth conditions, during IFN-γ-induced persistence, only bands C (CT157) and M (CT413 - PmpB) are up-regulated thus suggesting a potential role in chronic C. trachomatis infection.

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Thèses sur le sujet « Chronic and acute diseases »

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