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MUDr. Michal Otáhal Biomechanický model interakce oběhu a ventilace za podmínek UPV Abstract: Conventional mechanical ventilation provides gas exchange in conditions of respiratory failure by application positive airway pressure in the respiratory system. Due to the significant change in pressure conditions inside the thorax during conventional artificial ventilation the circulation can be significantly affected. Recruitment maneuver (RM) techniques can be a part of ventilation strategy in patients with the Acute Respiratory Distress Syndrome (ARDS), that are used to re-aerate collapsed parts of the lung parenchyma. During these RMs a significantly higher airway pressure is used than in protective ventilation strategy, which can limit the flow through the lung capillary network and can significantly affect the systemic hemodynamics of the patient. The aim of this work was to develop an optimized animation model of ARDS, then to compare the influence that has the application of different types of recruitment maneuvers on hemodynamics and to create a biomechanical simulation model of interaction and blood circulation and its verification with data obtained during the implementation of different types of RM in the experimental animal ARDS model. Results from the experimental animal model and simulations...

jdelvall@upc.edu.pe / Acute respiratory infections are responsible for high morbi–mortality in Peruvian children. However, the etiological agents are poorly identified. This study, conducted during the pandemic outbreak of H1N1 influenza in 2009, aims to determine the main etiological agents responsible for acute respiratory infections in children from Lima, Peru. Nasopharyngeal swabs collected from 717 children with acute respiratory infections between January 2009 and December 2010 were analyzed by multiplex RT-PCR for 13 respiratory viruses: influenza A, B, and C virus; parainfluenza virus (PIV) 1, 2, 3, and 4; and human respiratory syncytial virus (RSV) A and B, among others. Samples were also tested with direct fluorescent-antibodies (DFA) for six respiratory viruses. RT-PCR and DFA detected respiratory viruses in 240 (33.5%) and 85 (11.9%) cases, respectively. The most common etiological agents were RSV-A (15.3%), followed by influenza A (4.6%), PIV-1 (3.6%), and PIV-2 (1.8%). The viruses identified by DFA corresponded to RSV (5.9%) and influenza A (1.8%). Therefore, respiratory syncytial viruses (RSV) were found to be the most common etiology of acute respiratory infections. The authors suggest that active surveillance be conducted to identify the causative agents and improve clinical management, especially in the context of possible circulation of pandemic viruses

Background. Medical imaging has played an important role in the diagnosis, progress monitoring and follow-up of most disease entities, in particular chest infections. The emergence of a novel chest disease poses an immediate challenge to the pillars of imaging, namely chest radiography and computed tomography. The characteristic imaging appearances, differential diagnoses and diagnostic pitfalls need to be established for correct diagnosis and appropriate management. The sensitivity and utility of the different imaging modalities will also need to be addressed. / In the event of an outbreak or epidemic, these challenges are made more difficult by an overwhelming number of patients and limited resources. In March 2003, we were faced with such a situation in our institution and the disease was later termed Severe Acute Respiratory Syndrome (SARS). / Patients in Hong Kong were treated with a combination of an antiviral agent and corticosteroids in addition to respiratory support. The majority of patients improved with treatment, although between 20--36% required treatment in an intensive care unit. / Problems and importance. This novel disease of high infectivity, morbidity and mortality posed a major threat to public health and a challenge to health authorities both locally and internationally. With regard to medical imaging, the following research questions were identified: (1) What are the imaging signs of this new disease? (2) Does chest imaging provide a high degree of sensitivity for diagnosing the infection? (3) Are the imaging signs disease-specific or are they similar to other pathology? (4) Does the progressive evolution of the imaging appearance correlate with the clinical status of the patient? (5) Could the imaging appearance be useful for predicting the final outcome? (6) Are there complications that require detection by imaging? / The lung parenchyma is the main site of infection and the resultant microscopic pathology included: pulmonary exudate, sequestration of macrophages, diffuse alveolar damage, proliferation of epithelial cells and hyaline membrane formation. Macroscopic features include alveolar consolidation in the early stages and later, organizing pneumonia or bronchiolitis obliterans organizing pneumonia. / These answers to these questions are essential to our understanding of the disease and to increase our diagnostic ability. (Abstract shortened by UMI.) / This newly emerged disease is a respiratory infection with a high morbidity/mortality and was found to be caused by a coronavirus (SARS CoV). By the end of the outbreak a total of 8098 probable cases of infection were reported worldwide, with a mortality rate of 9.6% (774 deaths). Hong Kong was one of the hardest hit regions, totaling 1755 probable cases of infection and 299 deaths by the end of the outbreak. / Antonio Gregory Ernest. / "September 2005." / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3745. / Thesis (M.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 245-258). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

Ventilator associated pneumonia (VAP) and acute respiratory distress syndrome (ARDS) are two respiratory conditions unique to mechanically ventilated patients. The diagnosis of these conditions, and therefore any subsequent treatment, are befuddled by uncertainty. VAP rates vary considerably according to the diagnostic or surveillance criteria used. The pathogenesis of ARDS is well understood but when the internationally agreed consensus criteria are employed, the histological hallmarks are absent about half the time, indicating a disconnection between the clinical diagnosis and what is known about the biology of this condition. It is argued that tests of biological function should be considered in addition to clinical characteristics in order to improve the utility of diagnosis. Given that the pathological sequelae of both VAP and ARDS are driven by an over exuberant host neutrophil response, the activated neutrophil was selected as a potential biological imaging target. Optical molecular imaging uses visible and near visible wavelengths from the electromagnetic spectrum to derive or visualize information based on the optical properties of the target tissue. Optical wavelengths are safe and cheap to work with, producing much higher resolution images than those relying on x-rays or gamma radiation. The imaging modality can be coupled with exogenously applied chemistry to identify specific biological targets or processes. The hypothesis that optical molecular imaging could be used to detect activated neutrophils in real time in the alveolar region of patients was tested. A bespoke optical molecular imaging agent called Neutrophil Activation Probe (NAP), designed in-house, was used to test the hypothesis. NAP is a dendrimeric compound delivered to the alveolar region of a patient in microdoses (≤100 micrograms), becoming fluorescent only on contact with activated neutrophils, and can be detected by optical endomicroscopy. Both the imaging agent and the endomicroscope are delivered to the distal lung via routine bronchoscopy. The agent was tested extensively in the laboratory to demonstrate function, specificity, and safety. Ex vivo testing took place using human and ovine lungs. A regulated dose escalation Phase I clinical trial of investigational medicinal product (CTIMP) in healthy volunteers, patients with bronchiectasis, and mechanically ventilated patients with a pulmonary infiltrate on chest radiography (NCT01532024) was designed and conducted. The aim of the Phase I study was to demonstrate the safety of the technique and to confirm proof of concept. In order to support the requirement for a technique that interrogates alveolar neutrophils two supplementary clinical studies were performed. Firstly, two VAP surveillance techniques (CDC surveillance and HELICS European VAP surveillance) were compared with clinically diagnosed VAP across consecutive admissions in two large tertiary centres for one year. Secondly, the utility of circulating neutrophils to permit discrimination between acute respiratory illnesses was examined. Blood samples from mechanically ventilated patients with and without ARDS underwent flow cytometric assessment using eight clusters of differentiation and internal markers of activation to determine neutrophil phenotype. All clinical studies received the appropriate regulatory, ethical, and/or Caldicott guardian approval prior to commencement. NAP became fluorescent only in the presence of three processes specific to neutrophil activation: active pinocytosis, progressive alkalinization of the phagolysosome, and the activity of human neutrophil elastase. High optical signal was detected following the application of NAP in the alveolar regions of explanted lungs from patients with cystic fibrosis, known to be rich in activated neutrophils. Using an ex vivo ovine lung ventilation and perfusion model optical signal was demonstrated following segmental lung injury. The safety and specificity of the technique in a small cohort of healthy volunteers and mechanically ventilated patients was demonstrated. The technique was tested on a small cohort of patients with bronchiectasis, which provided the first opportunity to obtain broncho-alveolar lavage samples for laboratory correlation. Fluorescent signal was shown in the lavaged neutrophils, labeling that could only have taken place in the alveolar region. The supportive clinical studies found the concordance between actual VAP events was virtually zero even though the reported VAP rates were similar. Furthermore, the rate at which clinicians initiate antibiotics for VAP was approximately five times higher than either surveillance VAP rate. The study of circulating neutrophils from the blood of healthy volunteers and mechanically ventilated patients with and without ARDS indicated circulating neutrophil activation phenotype was not capable of discriminating between clinically diagnosed ARDS and other acute respiratory illnesses. In summary, an ambitious programme of work was completed to develop and support an optical molecular imaging technique that meets the rigorous requirements for human application and can be applied at the bedside to yield immediate visual results. The spatiotemporal relationship of neutrophil activation in real time both in the laboratory and in volunteers and patients was visualized. The visualization of neutrophil activation at such a resolution has never been achieved before in humans, healthy or unhealthy. The Phase I study was not powered to determine utility but recruitment has begun to a Phase II CTIMP (NCT02804854) to investigate the utility, accuracy, and precision of the imaging technique in a large cohort of mechanically ventilated patients. Ultimately, it is proposed that the technique will facilitate diagnosis, stratify patients for treatment and monitor treatment response using this technique.

Infecções por Plasmodium sp. podem levar a complicações pulmonares denominadas síndrome do desconforto respiratório agudo (SDRA). O modelo experimental, que utiliza o parasita murino Plasmodium berghei ANKA (PbA) e camundongos da linhagem DBA/2, é empregado no estudo de mediadores imunológicos e fatores que propiciam o estabelecimento das lesões pulmonares. Camundongos DBA/2 infectados com PbA foram classificados de acordo com a causa de morte como SDRA ou HP (hiperparasitemia). In vivo foi analisada a distribuição do parasita e os pulmões foram coletados para análise da capacidade respiratória, histopatologia, permeabilidade vascular, qRT-PCR e imunoistoquímica e efeito anti-inflamatório (Dexametasona - Dexa). In vitro, células endoteliais pulmonares foram submetidas a diversos estímulos. Verificamos que há acúmulo de PbA nos pulmões de DBA/2 com SDRA e que TNF e IFN-γ aumentam a citoadesão, expressão de ICAM-1, VCAM-1 e EPCR. A inibição de TNF diminui a adesão e dexa protege os animais através da diminuição de fatores inflamatórios, EPCR e inibição da abertura de junções interendoteliais. A intervenção da citoaderência e da permeabilidade vascular com o uso de corticosteróides, pode ser um importante alvo para o tratamento e a prevenção da SDRA. / Infections by Plasmodium sp. can lead to pulmonary complications called acute respiratory distress syndrome (ARDS). The experimental model, using the murine parasite Plasmodium berghei ANKA (PbA) and DBA/2 mice, is used no study of immunological mediators and factors that allow the establishment of lung lesions. DBA / 2 mice infected with PbA were classified according to cause of death as ARDS or HP (hyperparasitism). In vivo the parasite distribution was analyzed, and the lungs were collected for respiratory capacity analysis, histopathology, vascular permeability, qRT-PCR, immunohistochemistry and anti-inflammatory effect (Dexamethasone-Dexa). In vitro, pulmonary endothelial cells were submitted to various stimuli. We found that there is accumulation of PbA in the lungs of DBA/2 with ARDS and TNF and IFN-γ increase cytoadhesion, expression of ICAM-1, VCAM-1 and EPCR. Inhibition of TNF decreases adhesion and dexa protects animals by decreasing inflammatory factors, EPCR and inhibiting the opening of interendothelial junctions. The intervention of cytoadherence and vascular permeability with the use of corticosteroids may be an important target for the treatment and prevention of ARDS.

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.

The objectives of this research study are: 1. To probe into the widespread period of severe acute respiratory syndrome. 2. To study on this highly contagious and rapid spread of this new kind of disease At the time when nearby emergency department of medical center breaks out a suspicion of nasocomial infection. First, our emergency department immediately formed a strict fever screening station. After comparing the outcome of the prevention and spreading of this disease by the set-up of the emergency fever station between the central and southern medical institution. The research period was from May 15, 2003to July 15, 2003. Our research targets made by the emergency fever station were around 3730 patients with a random selection of 300 cases. This research uses the structure of fever screening measurement questionnaires to gather information and then adapted the EP1-INFO 10.0 version of statistical analysis. The results of the research are as follows: 1. Chief complaint of sore throat (38.3%) and fever (17%) fitted to the clinical symptoms of SARS. In relation to SARS before and after the spread of the disease, there are still other complaints such as the gastrointestinal system (18.7%) and cardiovascular disease (16.7%) that showed no obvious difference. 2. During the period of emergency fever screening station, an additional 50% of manpower are being arranged to screen probable or non-probable affected cases. (from the 300 randomly selected cases) 3. There are no obvious difference showed after comparing the outcome of the prevention and spreading of this disease by the set-up of the emergency fever center between the central and southern medical institution. 4. After tallying the number of doctors and nurses participated in screening procedure and number of non-medical staff developed similar symptoms to SARS, we can see the result of total number of medical staff from the emergency fever screening station that can successfully control the spread and prevention of the disease, making it the standard and model in the prevention and control of other communicable disease in the future. Key words: Severe acute respiratory syndrome, fever screening station, emergency room, emergency task force

This cross-sectional, community-based study was designed to compare the health outcomes of 2 - 5 year-old children in different types of preschools. The Integrated Child Development Services (ICDS), run by the government of India, created a system of preschools, called anganwadis, to combat malnutrition, provide health education for mothers, and preschool for children 2 - 6 years old in 1975. Many children attend their local anganwadis, while others attend private schools, and others do not attend school at all. A pre-tested questionnaire was used to interview 125 urban and 130 rural mothers regarding their knowledge, attitudes, and practices about acute diarrheal disease (ADD), acute respiratory infections (ARI), and nutrition (practice only) as they pertained to their 2 - 5 year-old child. Two-week and four-week health recalls were obtained to determine which children had experienced diarrhea or ARIs during those time periods. Anthropometric measurements of the children (weight, height, upper-arm circumference) were collected whenever possible. The study was carried out in an urban slum rural villages surrounding in and surrounding Bangalore, India. Data was collected from March through May of 2009. Through data analysis, KAP and child health scores were calculated to compare four preschool types: anganwadis receiving health check-ups from a medical college, anganwadis not receiving the medical check- ups, other (non-anganwadi) preschools and children not attending preschool. Analyses were performed to identify gaps in KAP, determine the impact of KAP on nutritional status, determine the impact of KAP on ADD and ARI, and determine if preschool type influences KAP scores. Children not attending preschool of any type are at higher risk of ADD, ARI, and being underweight. These children have mothers with the lowest attitude scores. Mothers of children in other preschools have the highest percentage of good knowledge and practice scores. Children who attend other preschools also have the lowest prevalence of underweight. This information can be useful in designing interventions for specific populations.

This thesis is based on studies in Butajira district in the south central part of Ethiopia and one study in the Ethio-Swedish Children's Hospital in Addis Ababa. The Butajira project has a continuous demographic surveillance system, established in 1987 in a sample of 10 communities with a total baseline population of about 30,000. The project includes the development and evaluation of a system for continuous registration of vital events and provides a baseline population and sampling frame for health related research activities. The thesis used different study designs within the surveillance system. A carriership study was undertaken to determine the potential bacterial respiratory pathogens among under-five children. A clinical study was done to investigate aetiological agents among young infants (below 3 months) with pneumonia, sepsis and meningitis in a hospital setting. Interview studies were carried out on mothers' perceptions of illness and practices in the care of children with acute respiratory infections. Within the surveillance system, patterns of under-five mortality were analysed. A nested case-referent design was applied to assess public health and behavioural determinants of mortality. A cohort study was performed among under-fives in three communities to estimate the magnitude of illness burden, particularly from ARI, as well as to assess determinants of ARI morbidity. Among 1126 under-five children, 85% were found to harbour H. influenzae, 83% M. catarrhalis and 90% S. pneumoniae in the nasopharynx. The hospital-based study isolated S. pneumoniae, Streptococcus group A, Salmonella group B, E. coli and H. influenzae in the age group below 3 months. The study of mothers' perceptions and practices, showed that mothers do know the symptoms of measles and whooping cough, while they do not recognize pneumonia as an illness entity and are not aware of fast breathing as an important sign of pneumonia. The mortality studies showed a high infant and under-five mortality rate. ARI was responsible for one fifth of the under-five mortality and almost one third of the infant mortality rate. Cause of death in the case-referent study was determined using a validated verbal autopsy method. Breast-feeding and supplementary feeding were demonstrated to be strongly protective when controlling for parental and environmental determinants of mortality. A one year prospective home surveillance study showed that illness was reported in 5.8% of 1,216 person-years. ARI contributed half of this illness load and was particularly associated with parental factors. Among sanitation factors, the absence of piped water was an important determinant of morbidity. Among housing factors, the type of roof and lighting source for the house, and among parental factors, illiteracy of either parents and having a farmer as a father, were found to be independently associated with increased morbidity. Among health and behavioural factors, preterm delivery and lack of immunization were associated with increased morbidity. The results of the studies of this thesis have been utilized to design an intervention case management package. The intervention study and evaluation of its impact is now on-going. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1994, härtill 7 uppsatser.</p> / digitalisering@umu.se