Abstract Respiratory distress syndrome (RDS) is a disease characterized by neonatal respiratory failure. It is principally caused by a deficiency of pulmonary surfactant, which is a lipoprotein mixture essential for reducing surface tension at the air-liquid interface of the alveolus. Prematurity is the major risk factor predisposing to RDS. Several pieces of evidence suggest the role of genetic factors in the susceptibility to this multifactorial disease. The present study was performed to determine whether polymorphisms of the surfactant protein SP-A1, SP-A2 and SP-B genes associate with RDS and to evaluate the relative contributions of genetic and environmental factors to the disease etiology. Allelic associations between the candidate genes and RDS were investigated using a matched and unmatched case-control and family-based study design. Disease concordance in monozygotic vs. dizygotic twin pairs was determined to measure the impact of heredity in RDS. SP-A and SP-B genes were shown to play a significant role in susceptibility to RDS. In very premature singleton infants born before 32 weeks of gestation, SP-A1 and SP-A2 allelic variations were associated with RDS, whereas the SP-B gene showed no direct association. Instead, the association between the high-risk (6A2, 1A0) or low-risk (6A3, 1A1/1A2) SP-A alleles and RDS was dependent on SP-B Ile131Thr variation, being restricted to a subset of infants carrying the homozygous genotype Thr/Thr. No allelic associations were evident in premature infants born after 32 weeks of gestation. RDS concordance was not significantly higher in monozygotic than in dizygotic twin pairs, implying a non-genetic disease etiology. However, the present study suggests that the concordance difference underestimates the extent of heredity. Twin pregnancies include intrauterine environmental factors that complicate the interpretation of the hereditary impact. SP-B Ile131Thr variation was associated with RDS in the first-born, but not in the second-born twins. The present results indicate that susceptibility to RDS is highly heterogeneous, involving complex environmental and genetic interactions. The degree of prematurity, singleton vs. multiple pregnancy, and birth order in a multiple birth are environmental confounders that determine disease subgroups. Genetic variations in the SP-A and SP-B genes account for part of the genetic component of RDS.

No description available.

Study objectives: To study the epidemiologic and clinical features of blastomycosis in northeast Tennessee. Design: Retrospective review of blastomycosis cases in the region from 1980 through 1995. Setting: Hospitals located in the Tri-Cities region of northeast Tennessee. Patients: Seventy- two patients with confirmed blastomycosis infection. Interventions: None. Results: During the 1980 to 1995 study period, we documented 72 cases of blastomycosis. The mean age was 52 years (range, 13 to 86 years), most were male (69.4%), and nine were immunocompromised. A possible environmental exposure was noted for 28 patients. Pulmonary involvement represented the most common site of infection (61 cases), but multiorgan involvement was common (17 cases). Most patients with pulmonary blastomycosis (66%) presented with a chronic illness, and radiologic findings usually revealed local consolidation or a mass-like lesion. Nine patients developed ARDS with an associated mortality rate of 89%, compared with a 10% mortality for non-ARDS pulmonary cases. Antifungal treatment regimens varied widely, with amphotericin B often used for sicker patients. An epidemiologic evaluation revealed that the mean yearly incidence rate for blastomycosis quadrupled between 1980 and 1987 (0.31 cases/100,000 population) and 1988 to 1995 (1.23 cases/100,000 population) (p=0.00001). Most new blastomycosis cases in the 1988 to 1995 period occurred in three counties in the region where significant new construction projects have been underway. Conclusion: Blastomycosis is endemic in northeast Tennessee and the number of eases is increasing, coinciding with major new construction in the region. Clinicians in the area must be alert to this condition.

Respiratory distress syndrome is a major cause of mortality among infants. Current therapies are limited in terms of invasiveness, cost, infrastructure, and leads to long term morbidities such as bronchopulmonary dysplasia. As a result a form of respiratory support termed as “artificial placenta” has been developed that allows natural development of lungs and avoids long term morbidities. The artificial placenta is connected via the umbilical vessels and provide pumpless respiratory support and is characterized by non-invasiveness, low cost and low infrastructure. Our group previously reported on a development of porous PDMS membrane artificial placenta. To build upon its development, one of the objectives of this thesis was to reduce the variation in the oxygen saturation of the input blood for testing the oxygenator. Another objective was to setup a mathematical model to predict the oxygen uptake in an oxygenating unit and use the model to optimize the geometric parameters of a design. The final objective was to improve the oxygen uptake of the oxygenating unit of the artificial placenta by redesigning the blood flow path and the membrane material. The experimental setup was improved to employ an active controller that actively maintained the oxygen saturation of the input blood for testing the oxygenator within a variation of ±3% of the set point for at least an hour. As compared to previous experimental setup the blood deviated from the set point by 9%. Later, the blood flow path in the oxygenator was redesigned from a flat height profile to a sloping height profile; and the PDMS membrane was reinforced with a thin steel mesh. Such changes improved the oxygen uptake at the operating pressure of 30 mmHg from 16 µL/min in case of an oxygenator with flat height profile and PDMS membrane to 26 µL/min in case of an oxygenator with flat profile and composite membrane. Finally, a mathematical model was developed that coupled oxygen uptake, pressure drop and membrane expansion. The model was validated against experimental results and was later used to optimize the configuration of the oxygenator with sloping profile and composite membrane. The predicted oxygen uptake of the optimized configuration at the operating pressure of 30 mmHg was 78.8 µL/min. / Thesis / Master of Applied Science (MASc)

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

No description available.

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...

Das Atemnotsyndrom (ANS) ist eine der häufigsten Atemwegserkrankungen von Frühgeborenen. Es ist bei Kindern, die nach der Geburt auf neonatologischen Intensivstationen betreut werden, häufig behandlungsbedürftig. Daher gibt es für das ANS einen etablierten und gut untersuchten Diagnostik- und Behandlungsalgorithmus. Zur Diagnostik dienen insbesondere eine klinische Untersuchung und eine Röntgenaufnahme des Thorax. Diese Röntgenuntersuchung ist allerdings mit verschiedenen Belastungen für Patienten und Personal verbunden, wobei vorrangig die ionisierende Strahlung zu nennen ist. Um diese Strahlenexposition bei den Kindern zu verringern, sollte in dieser Arbeit untersucht werden, wie exakt die Diagnosestellung des ANS mittels Lungenultraschall möglich ist. Zusätzlich sollte analysiert werden, ob die Ergebnisgenauigkeit des Lungenultraschalls beim ANS von bestimmten Faktoren abhängig ist und wie stark die klinische Symptomatik der Kinder mit dem bildmorphologischen Schweregrad des ANS übereinstimmt. In dieser Promotionsarbeit wurden 65 Neu- und Frühgeborene der neonatologischen Intensivstation der Universitätsklinik Leipzig retrospektiv untersucht. Dabei konnten wir zeigen, dass die bildmorphologischen Ergebnisse der Neonatologen und Radiologen häufig miteinander übereinstimmten. Die Ergebnisgenauigkeit war besonders hoch, wenn die Kinder ein geringes Gestationsalter aufwiesen, mit einer Atemhilfe versorgt waren oder zusätzlich Sauerstoff mit einer FiO2>0,25 erhielten. Der Lungenultraschall war nur in geringem Ausmaß vom jeweiligen Untersucher abhängig. Die Höhe der FiO2 war am besten geeignet, um den klinischen Schweregrad des ANS abschätzen zu können. Aufgrund der guten Studienlage und unserer exzellenten Ergebnisse empfehlen wir die Verwendung des Lungenultraschalls als zusätzliche Untersuchungstechnik bei der ANS-Diagnostik. Als alleinige Diagnostik ist die Lungensonographie besonders bei der Verlaufs- und Therapiekontrolle des ANS geeignet.

No description available.

Class of 2012 Abstract / Specific Aims: The purpose of this study is to evaluate and compare clinical outcomes and cost involved with use of poractant versus beractant for the treatment of respiratory distress syndrome (RDS) in a level III, neonatal intensive care unit (NICU) within an academic medical center. Methods: This retrospective cohort study included patients if they were admitted to the NICU for RDS between April 1, 2010 to November 30, 2010 and December 1, 2010 to June 30, 2011 treated with beractant and poractant respectively. Patients were excluded from the study if they were greater than 35 weeks gestational age and survived less than 48 hours. This is a review and the information needed from the patients was submitted in a data extraction form. Data collected included demographic variables (age, birthweight, birth length, gender, and race/ ethnicity), FiO2 measurement, mechanical ventilation time, length of hospitalization in the NICU, the incidence complications in the first 28 days, number of doses given, use of the nasal CPAP, concurrent complications or comorbidites such as pulmonary hemorrhage, bronchopulmonary dysplasia, patent ductus arteriosis, intraventricular hemorrhage, and retinopathy of maturity. Main Results: Data from 27 neonates in beractant and 13 in poractant groups were collected. The FiO2 measurements in both groups were generally similar. However, FiO2 was consistently lower in the poractant group. (p = 0.044 from a runs statistical test) Conclusions: The FiO2 measurement is poractant group was lower compared with beractant group, however the difference was noted to be not statistically significant.