Staphylococcus aureus is a pulmonary pathogen associated with substantial morbidity and mortality. It is a common complication of influenza and SARS CoV2 infection, chronic obstructive pulmonary disease, cystic fibrosis and is a major cause of ventilator associated pneumonia. The prevalence of this specific organism as a respiratory pathogen has been attributed to its many gene products that thwart innate immunity. However, vaccines targeting virulence determinants have failed to be protective in humans, suggesting that other bacterial or host factors are also critical in pathogenesis. We postulated that S. aureus that are able to persist in the lung must adapt to substrates that are especially abundant. Here we show that among the many potential carbon sources in the infected airway, S. aureus is directed by carbon catabolite repression (CCR) to utilize proline. By following transcriptomic and metabolomic changes over the initial course of infection by human clinical isolates of S. aureus, we established that CcpA and CcpE upregulate expression of the S. aureus collagenase (scpA) and proline transporter (putP). In response to infection, airway fibroblasts synthesize collagen, of which proline is a major component. Host-adapted S. aureus is thus poised to ingest and metabolize newly available proline which fuels oxidative metabolism via the TCA cycle, outcompeting strains that have not made this metabolic transition. Thus, clinical settings characterized by airway repair processes and fibrosis provide a milieu that is intrinsically supportive of S. aureus infection.

No description available.

Class I antiarrhythmic drugs, such as lidocaine, quinidine and procainamide, are known to be effective membrane stabilizers. However, the mechanism of such "membrane stabilization" has not been elucidated. In the present study we found that all three drugs are powerful scavengers of hydroxyl! radical. In addition, lidocaine was found to be a quencher of singlet oxygen. These drugs are also found to inhibit NADPH-dependent lipid peroxidation in bovine lung microsomes in a dose dependent manner. Since oxyradicals are implicated in the lipid peroxidation process and antiarrhythmic drugs were found to scavenge/quench reactive oxygen species, we proposed that the membrane Stabilizing effects of antiarrhythmic drugs may, in part, be due to their antioxidant properties. Ischemia-reperfusion injury has been studied in many organs. Despite the evidence of functional, metabolic and structural abnormalities during reperfusion, the precise mechanism of reperfusion lung injury remains obscure. Data from the organ models suggest that toxic oxygen metabolites play an important role in the mechanism of reperfusion tissue injury. Lidocaine has also been shown to be clinically valuable for the treatment and prevention of ventricular arrhythmia occurring after surgical correction of myocardial infraction. We found that the class I antiarrhythmic drugs are effective in ameliorating post-ischemic lung reperfusion injury in an ex vivo perfused rat lung model exposed to both normoxic and hyperoxic conditions. Since phagocytes are known to generate reactive oxygen species and play an important role in causing irreversible oxidative tissue injury during reperfusion of organs, we examined the role of antiarrhythmic agents on macrophage function. We found that these drugs inhibit superoxide and hydrogen peroxide production in stimulated macrophages in a dose dependent manner. The diminished production of superoxide was found to be not due to the inactivation of superoxide generating NADPH-oxidase enzyme but by inhibition of the phagocytosis process by these drugs The results of these studies indicate that the antiarrhythmic drugs, such as, lidocaine, quinidine and procainamide, are effective antioxidants and can protect biomembranes against lipid peroxidation injury and post-ischemic reperfusion injury of the lung. We have investigated the mechanism(s) of action of these drugs in ameliorating oxidative tissue injury and found that these drugs are not only effective in removing reactive oxygen species but also cause inactivation of pulmonary macrophage from inappropriately generating reactive species of oxygen. The fundamental knowledge derived from these Studies could lead to enhanced functional improvement of patients following cardiopulmonary bypass, pulmonary arterial embolectomy and acute respiratory distress syndrome, all of which undergo a period of elective/induced ischemia and reperfusion or oxidative stress. / Ph. D.

Hospital readmission is prevalent among people with chronic obstructive pulmonary disease (COPD), particularly among older people in Hong Kong. Evidence shows that hospital readmissions exert a considerable impact on patients. Studies in this area primarily identify various associative factors based on the perspectives of health professionals. However, these factors are inadequate in illustrating the needs of older people and in illuminating the phenomenon of hospital readmissions. A thorough understanding of the issue can be achieved if the related experiences are interpreted from the perspective of the patients and in terms of their context. Understanding of their experiences has paramount significance in uncovering the unmet needs of patients and in informing the provision of healthcare services. Yet, there is a dearth of studies unfolding the experiences of Chinese older people. / This study aimed to explore and describe the lived experience of hospital readmissions of Chinese older people with COPD and to identify Chinese socio-cultural influences on the experience. Understanding was acquired through descriptive phenomenology. Twenty-two Chinese older people aged 62 to 89 were recruited by purposive sampling. They had been readmitted 4 to 14 times in the previous year. The older people were interviewed once during their hospitalization, and their readmission experiences were elicited from these unstructured interviews. Narrative descriptions were analyzed using the phenomenological method described by Giorgi (1985). / The general structure of the lived experience of hospital readmissions of Chinese older people with COPD reveals that older people refrain from unnecessary readmissions because they regard hospital care as the last resort in relieving breathlessness. When their breathlessness becomes intolerable, they perceive the urgency of surviving the distress. Craving for survival, they seek hospital readmission, which provides them immediate relief from the imminent threat. After being readmitted to a hospital, they feel powerless when their need for hospital care is disregarded by their doctors. Considering themselves as demanding to their families in daily lives, older people remain conscious of relieving their burden during their periods of hospital readmission because they regard this as the only opportunity to relieve their burden. Older people come to realize hospital readmissions are unavoidable after they put every effort to refrain from it but hospital care remains necessary. They further rationalize hospital readmissions as inevitable and resign themselves to it because of their perception of aging, doctors’ accounts of COPD, experience with and knowledge of the disease, and belief in fate. This acceptance of the inevitability of hospital readmissions precipitates an attitudinal shift toward the belief of living for the moment. Their past experiences inspire them to be satisfied with the current state of living and engage the present. This positive outlook enables them to embrace the experiences of hospital readmissions into their lives. Six invariant constituents emerged from the lived experience. The constituent “refraining from unnecessary readmissions” describes how older people manage their diseases in relation to hospital readmissions. “Craving for survival” explains why they seek hospital readmissions. “Feeling being disregarded and powerless” and “being conscious of relieving burden to families” characterize their experience of hospital readmissions. “Resigning to hospital readmissions” illustrates how they understand the recurrence of this phenomenon and “living for the moment” illuminates how they live with their experiences. / A deep understanding of hospital readmissions is embodied in the experiences of older people. The findings emphasize that hospital readmissions among Chinese older people are complex experiences shaped by their sociocultural context. The meanings of hospital readmissions to older people are influenced by their assumption of a submissive patient role, collectivism, external attribution style, and past life experiences. Although older people appear to accept and cope well with hospital readmissions, this study uncovers their needs as they move to and fro the hospital and home. The findings of this study offer implications in promoting the wellness of Chinese older people as they go through this revolving door. / 再次住院在患有慢性阻塞性肺病人士中相當普遍，尤其是在中國老年患者。研究證據顯示再次住院對病人有很大的影響。現有的研究偏重於從醫務人員角度尋找不同的關聯因素，但該些因素並不足以反映老年人的需要以及解釋再次住院的現象。只有透過病人的觀點以及結合他們的背景來闡釋這些相關經驗，才能作出深入了解。了解病人的再次住院經驗有助於找出病人的需要以及指引醫療服務的提供。然而，有關中國老年人再次住院經驗的探討相當缺乏。 / 是次研究目的是探討和描述患有慢性阻塞性肺病的中國老年人再次住院的體驗，以及認識中國社會文化對再次住院經驗的影響。研究採用描述現象學方法。研究以立意抽樣方式選取了22名62至89歲的中國老年人。他們在去年入院次數為4至14次。這些老年人在住院期間均接受一次非結構式訪談以了解他們的再次住院經驗。這些敘述性描寫再按 Giorgi (1985) 的現象學方法作出分析。 / 患有慢性阻塞性肺病中國老年人再次住院的體驗的通用結構顯示他們避免不必要的再次住院，因為他們將住院護理視為紓緩呼吸困難的最後方法。當他們的呼吸困難惡化至無法忍受，他們會感受到從危病中活下來的迫切性。因著渴望生存的意識，他們尋求再次住院以即時消除緊迫的生命威脅。再次入院後，對於醫生漠視其住院護理的需要，他們感到無力。由於考慮到他們在日常生活中對家人的需求頗多，老年人以再次住院其間來減輕家庭負擔，因他們視這其間為唯一能減輕家庭負擔的機會。儘管老年人盡能力以避免再次入院，但他們依然需要住院護理，老年人逐漸意識到再次住院為無可避免。由於老年人對於老化的感知、醫生對慢性阻塞性肺病的解明、患病經驗和對疾病的相關知識以及相信命運的看法，他們更將再次住院合理化為無可避免並順從。接受再次住院為無可避免促成他們的態度轉變為活在當下。過去的經驗令他們對目前的生活感到滿意並希望活在當下。這個正面想法令他們將再次住院接納為生活的一部份。六個不變組成要素呈現於老年人的再次住院體驗當中。組成要素「避免不必要的再次住院」描述老年人如何管理慢性阻塞性肺病以避免再次住院。「渴望生存」解釋了他們尋求再次住院的原因。「感到被忽略和無力」以及「減輕家庭負擔的意識」敘述了他們再次住院的經驗。「順從再次住院」說明了他們對再次住院現象發生的理解，而「活在當下」說明了他們如何接納再次住院經驗。 / 對於再次住院的深入了解具體表現於老年人的經驗當中。是次研究結果強調，老年人再次住院是由他們的社會文化背景塑造而成的複雜經驗。對於老年人而言，再次住院的意義受到他們對順從性病人角色的假設、集體主義觀念、外部歸因以及過往的生活經驗所影響。雖然老年人似乎接受並適應再次住院，是次研究發現了他們在這現象中的需要。研究結果對於促進再次住院的中國老年人的健康帶來新的啟示。 / Tang, Wing Ki. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2015. / Includes bibliographical references (leaves 342-393). / Abstracts also in Chinese. / Title from PDF title page (viewed on 05, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Thesis (PhD (Pathology. Medical Microbiology))--University of Stellenbosch, 2005. / There has recently been a significant transformation in the medical world, in particular regarding the relation between the mind/health and mind/illnesses. The changes are briefly a revolution whereby the new approach sees the development of an illness as an interaction between the psychological, biochemical and physiological factors. Music, which is used as a clinical intervention, is perceived first through the brain, affirms this interaction between the body systems, as well as having the capacity to modify the mind and thus the biochemistry of the body. The aim of this study was essentially to supply empirical data by measuring selective parameters while the patients were receiving music intervention during the physiotherapeutic treatment for pneumonia and bronchitis. Forty adult patients who were divided into an experimental and control group, according to a random scale, participated in the research. The dependant variables that had shown significant changes amongst the experimental group after three days of physiotherapeutic treatment were as follows: the cortisol, the cortisol: DHEA ratio plasma levels, the POMS scale (that measures different moods), the peak flow measurements of the lung functions and the immune parameters, namely, CD4+ : CD8+ ratio and B-cells. The results showed that the experimental group that was exposed to the acoustic stimuli of the Magnificat in D, BWV 243 of JS Bach, experienced a more positive mood and lower cortisol levels, while the immune markers as well as the peak flow of the lungs had improved. The results of the control group showed significant implications, in that its cortisol levels increased and the POMS subscale of anger and depression showed no significant change, while the tension decreased significantly. This research provided sufficient scientific evidence to confirm the concept of a bidirectional communication between the brain and the immune system. It also showed clearly that music had the capacity to modify emotional conditions, which again influenced the endocrine and autonomic nervous system and modulated the immune systems.

The problem of this study is to determine the vitamin B-6 status of patients who have chronic obstructive pulmonary disease (COPD). Erythrocyte aspartate transaminase assay was the method for measuring vitamin B-6 status. The vitamin B-6 status was examined in thirty subjects (ten COPD subjects and twenty control subjects). An unpaired t-test was used to compare the vitamin B-6 status of the COPD group versus the control group. Four determinants (percentage stimulation, ratio of basal to stimulated activity, basal activity, and stimulated activity) were used to determine vitamin B-6 status in both groups of subjects. Percentage stimulation and ratio of basal to stimulated activity were not significantly different (control group versus COPD group) at the .05 level. However, two of ten COPD subjects had values for percentage stimulation that were two standard deviations above the mean, indicating a poor B-6 status. In contrast, basal activity and stimulated activity of erythrocyte aspartate transaminase were found to be significantly lower at the .05 level in the COPD group than the control group. Therefore, the COPD subjects as a group had some biochemical characteristics of a lower level of vitamin B-6 than the controls.

Orientador: Irma de Godoy / Coorientador: Susana Erico Tanni Minamoto / Coorientador: Camila Renata Corrêa / Banca: José Antonio Baddini Martinez / Banca: Mariana Gobbo Braz / Banca: Oliver Augusto Nascimento / Banca: Ângela Victoriano de Campos Soares / Resumo: Foi realizado estudo transversal para avaliar e comparar a associação entre estresse oxidativo e estado inflamatório e suas relações com a força muscular, a massa muscular sistêmica, a capacidade funcional de exercício e o estado geral de saúde em tabagistas, pacientes com doença pulmonar obstrutiva crônica (DPOC) leve/moderado e controles não tabagistas. Foram avaliados 32 tabagistas ativos (carga tabágica >10 anos/maço) sem DPOC, 32 pacientes com DPOC leve/moderado [tabagistas ativos ou ex-tabagistas (carga tabágica >10 anos/maço)] e 32 indivíduos não tabagistas. Todos os indivíduos foram submetidos à avaliação clínica e do estado tabágico, espirometria pré e pósbroncodilatador, oximetria de pulso e as concentrações de mediadores inflamatórios [proteína C-reativa (PCR), interleucina (IL) 6, receptores do fator de necrose tumoral alfa (TNFR1 e TNFR2)] e indicadores de estresse oxidativo [produtos finais de glicação avançada (AGEs) e receptor solúvel do produto final de glicação (sRAGE)] foram avaliadas no soro. Foi realizada avaliação da composição do corpo por bioimpedância, da força muscular periférica por dinamometria, da capacidade funcional de exercício (distância percorrida em seis minutos) e da avaliação do estado geral de saúde, por meio do Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) e da Escala Hospitalar de Ansiedade e Depressão (HAD). Tabagistas (p<0,001) e pacientes com DPOC (p<0,001) apresentaram valores superiores de AGEs quando comparados aos controles. Não houve diferença estatisticamente significante entre tabagistas e pacientes com DPOC. As concentrações de sRAGE não diferiram entre os grupos (p=0,92). Tabagistas (p=0,01) e pacientes com DPOC (p=0,01) apresentaram valores superiores da PCR em comparação aos controles, sem diferenças nas demais comparações. As concentrações de IL6 (p=0,07) e TNFR1 (p=0,07) não diferiram entre os grupos. Os valores... / Abstract: The aim of this study was to evaluate the association between oxidative stress and inflammatory markers and their relationship with muscle strength, systemic muscle mass, exercise capacity, quality of life in smokers, mild/moderate COPD patients and nonsmokers controls. Were evaluated 32 active smokers (smoking history> 10 pack/years) without COPD, 32 mild/moderate COPD patients [current smokers or former smokers (smoking history> 10 pack/years) and 32 nonsmokers. All individuals underwent to medical and smoking status evaluations, spirometry pre and post-bronchodilator and pulse oximetry. The concentration of inflammatory mediators [C-reactive protein (CRP), interleukin (IL) 6, and tumor necrosis factor-alpha receptors (TNFR1 and TNFR2)] and indicators of oxidative stress [advanced glycation end-products (AGEs) and soluble receptors for advanced glycation end-products (sRAGE)] were measured in serum. We assessed body composition by bioimpedance, peripheral muscle strength by dynamometry, exercise capacity (six minutes walk distance) and the health status through the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HAD). Smokers (p<0.001) and COPD patients (p<0.001) had higher values of AGEs when compared to controls there was no statistically significant difference between smokers and COPD patients. The sRAGE concentrations did not differ between groups (p=0.92). Smokers (p=0.01) and patients with COPD (p=0.01) showed higher values of CRP compared to controls, there was no statistical significant difference between smokers and COPD groups. The concentrations of IL-6 (p=0.07) and TNFR1 (p=0.07) did not differ between groups. Regarding concentrations of TNFR2, COPD patients showed higher values when compared to smokers (p=0.004) and controls (p=0.004). We identified positive association of smoking (p=0.04), CRP (p=0.03) and IL6 (p=0.03) with the concentrations of AGEs. The ... / Doutor

Includes bibliographical references. / 1 v. (various foliations) : ill. (some col) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Community Medicine, 1994

A case control study was performed in 6 cotton mills in KwaZulu-Natal, South Africa. The study used questionnaire and pulmonary function testing results to categorise respiratory symptoms in 52 exposed symptomatic, 30 exposed asymptomatic and 46 unexposed control subjects. These categorisation results were used to explore the relationship between serum IgG subclasses and cotton-specific IgG to byssinosis. No definitive relationships between the serum IgG subclasses and clinical and functional symptoms of byssinosis were found . Whereas, exposed symptomatic (22.72 mg All) subjects had significantly higher (P = 0.01) mean specific IgG concentrations than exposed asymptomatic (15.02 mg All) or unexposed control (13.08 mg All) subjects. A pathoaetiological or marker-aetiological role is indicated for specific IgG in the development of byssinosis. The findings of this research challenged the status quo in terms of the accepted aetiological pathways of byssinosis. In turn the acceptance of a different aetiological pathway provided a possible answer to the varying presentation of the disease and by implication contested the current definition of byssinosis. / Thesis (M.Med.Sc.)-University of Natal, Durban, 2002.

[Truncated abstract] Respiratory system impedance (Zrs) is commonly measured at low to medium frequencies (0.5 - 40 Hz) to infer structural and physiological information about the respiratory system. Coupled with the use of mathematical models of the lungs, Zrs has been used to partition the behaviour of the conductive airways and the respiratory tissues. High-frequency (HF) Zrs beyond 100 Hz has been comparatively less studied and understood. Past work has revealed spectral features at high frequencies termed antiresonances, marked by peaks in the real part of Zrs, often coinciding with zero-crossings in the imaginary part. It has been shown that the first occurrence of antiresonance in humans primarily reflects the contribution of the airways, and is a property of sound wave propagation in the airways. Also, the first antiresonance is altered in diseases such as chronic airflow obstruction, and wheeze in infants. The main aim of this project is to shed further understanding about the first antiresonance, via the behaviour of two parameters characterising this feature of the HF spectrum: the frequency at which the first antiresonance occurs, far,1, and the magnitude of the real part of Zrs at this frequency, Rrs(far,1). In our studies, Zrs is measured as an input impedance using the forced oscillation technique with a loudspeaker-in-box and wavetube setup, and employing pseudorandom frequency signals. We studied the effects of altered lung conditions, first in an animal model, then progressed on to humans. v vi In the rat, we found that both far,1 and Rrs(far,1) tended to decrease together with increasing lung volume. With methacholine(MCh)-induced bronchoconstriction, rats showed increases in far,1 and Rrs(far,1) with increasing MCh dose, but these occurred at higher doses compared to increases in airway resistance. The changes in these HF parameters were independent of the changes in tissue properties. ... It was found that in a group of patients with emphysema, VDRrs(far,1) was significantly more negative, potentially due to alterations to airway dimensions and wall properties. Furthermore, VDRrs(far,1) was correlated with extent of obstruction and hyperinflation, suggesting a relationship with severity of emphysema. These results show that the first antiresonance reflect changes in the airways, and its measurement shows promise as a clinical tool, in its potential as an easy-to-perform assessor of conditions in which the airways are altered. Keywords: antiresonance, respiratory input impedance, high frequencies, emphysema