Immune cells such as neutrophils and monocytes enter tissues after tissue damage and clear cell debris to allow repair cells such as fibroblasts to close the wound. Monocytes also differentiate into fibroblast-like cells called fibrocytes to mediate wound healing, similar to fibroblasts. However, in abnormal wound healing such as acute respiratory distress syndrome (ARDS) and fibrosing diseases, the accumulation of immune cells such as neutrophils or fibrocytes become detrimental to health. In ARDS, neutrophils accumulate in the lungs and causes additional damage by producing reactive oxygen species (ROS). In fibrosing diseases, increased fibrocyte differentiation is one of the causes that increase extracellular matrix deposition, which leads to severe scar tissue build up. Since there are no effective treatments for ARDS or fibrosing diseases, understanding the regulation of neutrophil activation or fibrocyte differentiation could be helpful to develop new effective therapies. The Gomer lab has found several factors that either promote or inhibit fibrocyte differentiation. The pro-fibrotic cytokines such as IL-4 and IL-13 potentiate fibrocyte differentiation while the plasma protein serum amyloid P (SAP), crosslinked IgG, and the pro-inflammatory cytokines IFN-γ and IL-12 inhibit fibrocyte differentiation. In this thesis, I have now shown that additional factors such as toll-like receptor 2 (TLR2) agonists and low molecular weight hyaluronic acid (LMWHA) inhibit fibrocyte differentiation, while high molecular weight hyaluronic acid (HMWHA) potentiate fibrocyte differentiation. The accumulation of neutrophils in the lungs is one of the major factors that debilitate the health of a patient in ARDS. Since neutrophils have Fc receptors, I examined the effect of SAP on neutrophil spreading, adherence, activation, and accumulation. SAP inhibits neutrophil spreading induced by cell debris and TNF-α induced adhesion, but SAP is unable to have any effect on classic neutrophil adhesion molecules or the production of hydrogen peroxide. SAP inhibits neutrophil accumulation in the lungs of bleomycin-injured mice. There is an exciting possibility of using SAP as a therapeutic agent to treat ARDS.

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Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisor: Angela P. Clark. Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 88-97).

Introduction: Limited facilities exist at rural hospitals for the management of newborn infants with respiratory distress syndrome (RDS). Furthermore, the secondary and tertiary hospitals are under severe strain to accept all the referrals from rural hospitals. Many of these infants require intubation and ventilation with a resuscitation bag which must be sustained for hours until the transport team arrives. Not only is lung damage inflicted by the prolonged ventilation, but transferring the infant by helicopter and ambulance is expensive. CPAP (continuous positive airway pressure), a non-invasive form of ventilatory support, has been used successfully at regional (Level 2) and tertiary (Level 3) neonatal units, to manage infants with RDS. It is cost-effective for infants with mild to moderate grades of RDS to be managed at the rural hospital instead of being transferred to the regional secondary or tertiary hospital. CPAP was introduced to Ceres Hospital, a rural Level 1 hospital, in February 2008 for the management of infants with RDS. Aim: To determine the impact of CPAP on the management of infants with RDS in a rural level 1 hospital and whether it can reduce the number of referrals to regional hospitals. Study setting: Nursery at Ceres District Hospital, Cape Winelands District, Western Cape. Study design: Prospective cohort analytical study with an historic control group (HCG). Patients and Methods: The study group (SG) comprised all neonates with respiratory distress born between 27/02/2008 and 26/02/2010. The infants were initially resuscitated with a Neopuff® machine in labour-ward and CPAP was commenced for those with RDS. The survival and referral rates of the SG were compared to an historic control group (HCG) of infants born between 1/2/2006 to 31/01/2008 at Ceres Hospital. Results: During the 2 years of the study, 51 neonates received CPAP (34 <1800g, 17>1800g). Twenty (83%) of the SG infants between 1000g and 1800g and 23 (68%) of the infants between 500g and 1800g survived. Those <1800g that failed CPAP, had either a severe grade of RDS which required intubation and ventilation or were <1000g. Seventeen (33%) of the infants that received CPAP, were in the >1800g group. Thirteen (76%) of these infants were successfully treated with CPAP only. The four infants that failed CPAP suffered from congenital abnormalities and would not have benefited from CPAP. There was no statistically significant difference in the survival between the SG and HCG (80%) (p=0.5490) but the number of referrals decreased significantly from 21% in the HCG to 7% in the SG (p=0.0003). No complications related to CPAP treatment, such as pneumothorax, were noted. The nursing and medical staff quickly became proficient and confident in applying CPAP and were committed to the project. Conclusion: CPAP can be safely and successfully practised in infants with mild to moderate RDS in a rural Level 1 hospital. The survival rate stayed the same as the HCG, even though a higher risk infants were treated in the SG. The transfers were significantly reduced from 21% to 7%. This resulted in significant cost savings for the hospital.

Made available in DSpace on 2014-06-11T19:30:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-02Bitstream added on 2014-06-13T19:40:09Z : No. of bitstreams: 1 gusman_pb_dr_botfm.pdf: 625469 bytes, checksum: 27745b379b0a215dafab05d5182357ac (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Desde sua primeira descrição, muito se investiu no melhor conhecimento da SARA, na identificação de sua etiologia, seus fatores de risco, seus mecanismos e mediadores, escolhendo-se métodos críticos de avaliação clínica que também pudessem definir o prognóstico. Com o objetivo de verificar se os efeitos da PEEP dependem da morfologia pulmonar, comparando sua resposta em três grupos de pacientes, descritos de acordo com os aspectos de hiperdensidades observadas nos cortes tomográficos, foram estudados 71 pacientes portadores de SARA, comparando-os a 11 voluntários sadios. Cada paciente foi submetido a exame tomográfico helicoidal de tórax em ZEEP e após implemento de PEEP de 10 cmH2O. Parâmetros hemodinâmicos e respiratórios foram mensurados nas mesmas condições. Hiperdistensão induzida pela PEEP e recrutamento alveolar foram quantificados por um software específico, Lungview®. Hiperdistensão ocorreu somente nos lobos superiores e se correlacionou significativamente com volume pulmonar caracterizado por uma densidade tomográfica de parênquima pulmonar variando entre -900 UH e -800 UH em ZEEP. Efeitos cárdio-respiratórios em PEEP foram semelhantes nos pacientes com SARA primária e secundária. O recrutamento alveolar induzido pela PEEP nos lobos inferiores se correlacionou de forma significativa com seu volume pulmonar residual. Recrutamento alveolar induzido pela PEEP foi maior nos lobos inferiores com atelectasias inflamatórias do que nos lobos inferiores com atelectasias mecânicas. A morfologia pulmonar acessada pelo exame tomográfico influenciou de forma significativa os efeitos da PEEP. Em pacientes com hiperdensidades difusas, a PEEP induziu recrutamento alveolar importante sem hiperdistensão, enquanto que nos pacientes com hiperdensidades localizadas, a PEEP induziu... / There has been some decades, a lot has been invested in the attempt of better knowledge of ARDS, characterizing in a more trustworthy way your aetiology, risk factors, its mechanisms and mediators, choosing critical methods of clinical evaluation that could also foresee the prognostic. To determine whether differences in lung morphology assessed on the CT scan influence the response to PEEP we study by a prospective study during a 53-month period in a fourteenbed surgical Intensive Care Unit of a university hospital, seventy-one consecutive patients with early ARDS. In each patient, a fast spiral thoracic CT scan was performed in ZEEP and after implementation of PEEP 10 cmH2O. Hemodynamic and respiratory parameters were also measured in the same conditions. PEEPinduced overdistension and alveolar recruitment were quantified by a specifically designed software, Lungview®. Overdistension occurred only in the upper lobes and was significantly correlated with the volume of lung characterized by a scanographic density ranging between -900 HU and -800 HU parenchyma in ZEEP conditions. Cardiorespiratory effects of PEEP were similar in patients with primary and secondary ARDS. PEEP-induced alveolar recruitment of lower lobes was significantly correlated with their resting lung volume. PEEP-induced alveolar recruitment was greater in the lower lobes with inflammatory atelectasis than in the lower lobes with mechanical atelectasis. Lung morphology assessed on the CT scan markedly influenced the effects of PEEP: in patients with diffuse hyperdensities, PEEP induced a marked alveolar recruitment without overdistension whereas, in patients with lobar hyperdensities, PEEP induced a mild alveolar recruitment associated with overdistension of previously aerated lung areas. These results... (Complete abstract click eletronic address below)