published_or_final_version / Paediatrics / Master / Master of Philosophy

A clinical need exists for a blood oxygenator and pumping system for the support of neonates with respiratory deficiencies. Such systems now available for support of adults are not suitable for neonatal patients. In vitro evaluation of a new blood oxygenator and blood pumping system was performed. The data obtained suggested that this system may be applicable to neonates. In vivo studies with rabbits to further analyze the new system were done. Preliminary data from these studies indicate that the new blood oxygenator and blood pump system may be applicable to supporting neonates with respiratory deficiencies. Suggestions for future development of this system are presented. / Master of Science

Leung, Wan Lun Fiona. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 179-204). / Abstracts in English and Chinese. / Abstract --- p.i / 中文摘要 --- p.v / Acknowledgement --- p.viii / List of Abbreviations and Symbols x --- p.vi / List of Tables --- p.xx / List of Figures --- p.xxi / Chapter CHAPTER ONE --- Introduction --- p.1 / Chapter 1.1 --- General Overview --- p.1 / Chapter 1.2 --- Necrotizing Enterocolitis (NEC) --- p.3 / Chapter 1.2.1 --- Epidemiology of NEC --- p.3 / Chapter 1.2.2 --- "Clinical Presentation, Diagnosis and Management of NEC" --- p.5 / Chapter 1.2.3 --- Pathophysiology of NEC --- p.9 / Chapter 1.2.3.1 --- Prematurity --- p.9 / Chapter 1.2.3.2 --- Bacterial Colonization --- p.12 / Chapter 1.2.3.3 --- Enteral Feeding --- p.15 / Chapter 1.2.3.4 --- Hypoxia and Ischemia --- p.16 / Chapter 1.2.3.5 --- Genetic Polymorphism --- p.17 / Chapter 1.2.3.6 --- Inflammatory Mediators --- p.20 / Chapter 1.3 --- Spontaneous Intestinal Perforation (SIP) --- p.24 / Chapter 1.3.1 --- Epidemiology of SIP --- p.24 / Chapter 1.3.2 --- "Clinical Presentation, Diagnosis and Management of SIP" --- p.26 / Chapter 1.3.3 --- Risk Factors of SIP --- p.28 / Chapter 1.3.3.1 --- Prematurity --- p.29 / Chapter 1.3.3.2 --- Use of Drugs --- p.30 / Chapter 1.4 --- Comparison between NEC and SIP --- p.32 / Chapter 1.5 --- Role of Cytokines in Pathogenesis of NEC and SIP --- p.38 / Chapter 1.6 --- Immunoregulatory Molecules of Interest in This Study --- p.46 / Chapter 1.6.1 --- Angiopoietin-2 (Ang-2) --- p.46 / Chapter 1.6.2 --- v-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog 2 (avian) (ErbB3) --- p.48 / Chapter 1.6.3 --- Type II Interleukin-1 Receptor (IL-1RII) --- p.52 / Chapter 1.6.4 --- Urokinase Plasminogen Activator Receptor (uPAR) --- p.54 / Chapter CHAPTER TWO --- Objectives --- p.57 / Chapter CHAPTER THREE --- Materials and Methodology --- p.58 / Chapter 3.1 --- Overview of the Experimental Procedures --- p.58 / Chapter 3.1.1 --- Investigation on the Profile of Circulatory Immunoregulatory Proteins in Plasma of NEC and SIP High Risk Neonates --- p.58 / Chapter 3.1.2 --- Investigation on the mRNA Expression Level of Targeted Immunoregulatory Molecules on Resected Intestinal Tissues in NEC and SIP Neonates --- p.58 / Chapter 3.1.3 --- Investigation on the mRNA and Protein Expression Levels of Targeted Immunoregulatory Molecules in Human Intestinal Cell Lines --- p.60 / Chapter 3.2 --- Reagents and Lab-wares with Their Sources --- p.61 / Chapter 3.3 --- Study Population --- p.63 / Chapter 3.4 --- Collection of Neonatal Whole Blood Samples --- p.65 / Chapter 3.5 --- Cytokine Antibody Array Analyses --- p.67 / Chapter 3.6 --- Enzyme-linked Immunosorbant Assays (ELISA) --- p.69 / Chapter 3.6.1 --- Angiopoietin-2 --- p.69 / Chapter 3.6.2 --- sErbB3 --- p.71 / Chapter 3.6.3 --- sIL-lRII --- p.72 / Chapter 3.6.4 --- suPAR --- p.74 / Chapter 3.7 --- Collection of Neonatal Resected Intestinal Tissues --- p.76 / Chapter 3.8 --- Resected Intestinal Tissue RNA Isolation --- p.78 / Chapter 3.9 --- Purity Assessment of the Purified Tissue RNA Samples --- p.80 / Chapter 3.10 --- Integrity Assessment of the Purified Tissue RNA Samples --- p.81 / Chapter 3.11 --- In vitro Stimulation of Human Enterocytes by Lipopolysaccharides (LPS) and/or Platelet Activating Factor (PAF) --- p.84 / Chapter 3.12 --- mRNA Expression Level Assessment of Selected Target Genes in Resected Intestinal Tissues and Human Intestinal Cell Lines --- p.86 / Chapter 3.12.1 --- Synthesis of First Strand cDNA --- p.86 / Chapter 3.12.2 --- Quantitative Polymerase Chain Reaction (qPCR) --- p.87 / Chapter 3.13 --- Statistical Analysis --- p.89 / Chapter CHAPTER FOUR --- Screening of Immunoregulatory Target Protein Molecules in Plasma of NEC and SIP Patients by Cytokine Array Analyses --- p.104 / Chapter 4.1 --- Results --- p.104 / Chapter 4.1.1 --- Screening of Detectable Immunoregulatory Target Molecules --- p.104 / Chapter 4.1.2 --- Selection of Target Molecules Based on the Fold Change in NEC or SIP Compared with Control Samples --- p.105 / Chapter 4.1.2.1 --- Similar Regulation of Target Molecules in Both NEC and SIP patients --- p.105 / Chapter 4.1.2.2 --- Differential regulation of Target Molecules in NEC and SIP Patients --- p.106 / Chapter 4.1.2.3 --- "Relative Normalized Expressions of Selected Circulatory Immunoregulatory Protein Molecules in NEC, SIP and Control Neonates" --- p.108 / Chapter 4.1.2.3.1 --- Anti-inflammation --- p.108 / Chapter 4.1.2.3.2 --- Pro-inflammation --- p.109 / Chapter 4.1.2.3.3 --- Cell Growth --- p.110 / Chapter 4.1.2.3.4 --- Wound Healing --- p.110 / Chapter 4.1.2.3.5 --- Angiogenesis --- p.111 / Chapter 4.1.2.3.6 --- "Anti-apoptosis, Cell Adhesion and Extracellular Matrix Organization" --- p.112 / Chapter 4.1.3 --- Further Selection of Novel Target Molecules Based on Statistical Significance and Fold Change of NEC versus SIP --- p.113 / Chapter 4.2 --- Discussion --- p.115 / Chapter CHAPTER FIVE --- Validation of Target Proteins in Plasma of NEC and SIP Patients by Enzyme-linked Immunosorbant Assay --- p.132 / Chapter 5.1 --- Results --- p.133 / Chapter 5.1.1 --- Demographic Data of the Study Group --- p.133 / Chapter 5.1.2 --- "Comparison of Plasma Levels of Target Proteins between NEC, SIP and Respective Controls" --- p.134 / Chapter 5.1.3 --- Longitudinal Study of the Pre- and Post-operative Target Proteins Levels in Plasma --- p.136 / Chapter 5.2 --- Discussion --- p.138 / Chapter CHAPTER SIX --- Investigation on mRNA Expression Levels of Target Immunoregulatory Protein Molecules in Intestinal Tissue and Intestinal Cell Lines --- p.151 / Chapter 6.1 --- Results --- p.152 / Chapter 6.1.1 --- mRNA Expression Levels of Target Molecules in the Diseased Margin of Resected Intestinal Tissues of NEC and SIP patients --- p.152 / Chapter 6.1.2 --- mRNA Expression Levels of Target Molecules in the Macroscopically Normal and Diseased Margin of Resected Intestinal Tissues of NEC and SIP patients --- p.154 / Chapter 6.1.3 --- mRNA Expression Levels of Target Molecules in Human Intestinal Cell Lines upon LPS and PAF Challenge --- p.156 / Chapter 6.1.3.1 --- FHs-74 Int Cell Line --- p.156 / Chapter 6.1.3.2 --- Caco-2 Cell Line --- p.157 / Chapter 6.2 --- Discussion --- p.158 / Chapter CHAPTER SEVEN --- General Discussion --- p.171 / Chapter 7.1 --- Overall Findings --- p.171 / Chapter 7.2 --- Limitations of Study --- p.174 / Chapter 7.3 --- Future Investigations --- p.177 / References --- p.179

This study was undertaken to investigate the relationship between Natural Killer cells and HLA-G at the placental barrier in HIV-I infected pregnant women and to establish the significance, if any, to in utero infection. Fifty-five HIV -I infected pregnant women were recruited into the study after consent was obtained. Blood samples were collected from both mothers and babies for viral loads and CD4+ cell counts. Placental samples were obtained from pregnancies at delivery and examined by immunoperoxidase immunohistochemistry methods using monoclonal antibodies to p24 antigens and Natural Killer (CD56+) cells. HLA-G expression was quantified using real-time polymerase chain reaction. Analysis of viral loads and CD4+ cell counts were undertaken in categories. No significant association was observed between the viral load of mothers and their CD4+ cell counts. Eighteen percent of the women in this study population had 5 log viral loads with a transmission rate of 0.27(95% Cl, 0.15 - O. 39). Maternal viraemia was significantly associated with transmission of infection to babies (p = 0.047). The odds ratio indicated that for every 1 log increase in maternal viral load the babies were 3.1 times more likely to acquire the infection (Exp (B) = 3.137 (95%CI, 1.015-9.696). Furthermore, the study found that a higher number of female babies were infected than males. Although not statistically significant the odds ratio indicated that female babies were 3.1 times more likely to become infected than males (Exp (B) = 3.110 (95%CI, 0.819-11.808). We report here the results of immunohistochemistry for p24 antigens and NK (CD56+) cells and compare them to the immunological responses of both mothers and babies at birth. HIV-1 antigens were detected in 94.5% of all placentas by immunohistochemistry. Infiltration of CD56+ was found in 98% of placental tissue. The analysis revealed that the presence of p24 antigens in placental tissue was not influenced by maternal viral load or CD4+ cell counts. Lower median NK cell values were observed in placentas of mothers with infected babies as compared with the uninfected cluster. Although not statistically significant, the risk of vertical transmission was increased 3.4 times more in placentas which had lower NK cell values. According to the odds ratio, babies CD4+ counts were affected by every 1 log increase in mother's viral load. Overall, maternal viral load emerged as a strong predictor for risk of infection from infected mothers to their infants. Our analysis indicated that female babies were 3.7 times more likely to acquire the infection than males. Using data obtained from real-time PCR we investigated the relationship between maternal viral load and the quantity of HLA-G expression (p = 0.045; 95%CI 1.029- 11.499). Logistic regression models revealed that mother's viral load was the strongest risk factor for vertical transmission. No statistically significant correlation was noted with HLA-G and viral transmission. However, the odds ratio indicated that the risk of infection increased by 1.3 with every 1 fold increase in HLA-G expression. An analysis of mother-to-child transmission rates by gender revealed that the odds ratio for transmission was 3.4 times more in female babies than in males. We then investigated the relationship between maternal viraemia and HLA-G expression. A positive correlation between maternal viral load and placental HLA-G was observed (p = 0.038). When gender susceptibility to HLA-G expression was explored a statistically significant association was observed in placental tissue of mothers with infected and uninfected male babies and HLA-G expression (p = 0.013). To conclude, the analysis found that HLA-G was up regulated 3.95 times more in placental tissue of mothers with infected babies than in mothers with uninfected babies. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2007.

Submitted in fulfilment of the requirements of the Degree of Master of Technology: Biomedical Technology, Durban University of Technology, 2013. / The purpose of the study was to evaluate knowledge and effects of Haemolytic Disease of the Newborn (HDN) in postnatal women from the Umgungundlovu District. Although the prevalence of HDN has declined because of prophylaxis from 45 cases per 10,000 births to 10.2 cases per 10,000 births but it is still a cause of infant and neonatal morbidity and mortality. The effects of the disease range from jaundice, kernicterus and in severe cases death. Methodology : An interviewer-administered questionnaire was used to obtain information about the knowledge and effects of HDN amongst postnatal women. The incidence rate was calculated using the number of cases that were found divided by the total number of deliveries during the study period. A total of 300 women were interviewed. SPSS version 19.0 was used to analyse data. Findings : Fifteen (15) of the 300 women had babies with confirmed HDN and only four of the 15 (26%) women had knowledge of HDN. Two hundred and eighty five women had babies with jaundice but were not affected by HDN and, of these women, 12 (4.2%) of them knew what HDN was. Overall, only 16 (5.3%) knew what HDN was. All 15 women who had babies with HDN indicated financial and emotional effects because of HDN. The total incidence was 0.09% for the first 12 months of the study period. Conclusion : Postnatal women with jaundiced babies lack knowledge of HDN and HDN has financial and emotional effects on these women. Although the incidence rate of HDN was found to be even smaller than previously reported, it still exists and threatens the lives of infants and neonates.

Gestational diabetes mellitus (GDM) and infant macrosomia are important obstetric health concerns for Aboriginal populations in Canada. Previous research in non-Aboriginal populations has established that GDM and macrosomia are associated with increased risk of fetal morbidity. Specifically, GDM is a risk factor for infant macrosomia, hypoglycemia, polycythemia, hypocalcemia, and hyperbilirubinemia. Furthermore, macrosomia is an independent risk factor for shoulder dystocia, clavicular fracture, brachial plexus injury, birth asphyxia and operative delivery. The main objectives of this study were to determine prevalence rates of GDM and macrosomia related neonatal complications for the James Bay Cree population of northern Quebec, and to identify risk factors for specific birth trauma injuries and metabolic complications in the population. The prevalence of macrosomia (≥4500 g) was 10.4%, and the estimated prevalence of GDM was 16.6% (95% CI 14.6-18.6) (n = 229/1379). Shoulder dystocia was the most common birth trauma event among the Cree, affecting 2.5% (n = 42/1650) of all Cree births, and 9.3% (n = 16/172) of macrosomic deliveries ≥4500 g. The prevalence of neonatal hypoglycemia was also high, affecting 8.8% (n = 144/1650) of all Cree newborns, and 18.1% (n = 34/192) of GDM deliveries. Macrosomia (BW ≥ 4500 g) was a significant risk factor for shoulder dystocia, clavicular fracture, hypoglycemia, and caesarean section delivery. After adjusting for maternal age, parity, and gestational age, GDM was identified as a significant risk factor for macrosomia (≥4500 g), hypoglycemia, polycythemia, and hypocalcemia. In summary, this study identified a high incidence of neonatal complications among the James Bay Cree compared with rates in the general North American population. These outcomes can be explained, in part, by high prevalence rates of gestational diabetes and infant macrosomia. Further studies to investigate the long-term consequences of GDM and

No description available.

The dramatic improvement of neonatal intensive care has produced vexing ethical and legal questions. One of the most striking issues is to determine whether the most defective neonates should be provided with intensive care and to what extent they should be treated. This thesis demonstrates that an attempt to answer this question and an analysis of the demands and limitations of a duty to treat defective neonates cannot properly occur without first considering the legal concerns and ethical issues surrounding the notion of "person". The author examines germane ethical theories and North-American jurisprudence to see what approaches and standards commentators and courts have adopted in this respect. This thesis demonstrates that in the context of the cessation or non-initiation of intensive care, the legal and moral status of very defective neonates remain ambiguous. In particular, the author suggests that a legal best interests analysis that includes quality of life considerations may actually involve the use of criteria similar to those supported by the authors of the controversial moral theories that negate the personhood of seriously handicapped newborns. The author ultimately concludes that a clear divide between the legal definition of the "person" and the moral and social perceptions of that term is misleading.

No description available.

A lesão nasal decorrente do uso da ventilação não invasiva (VNI) é um evento adverso cada vez mais comum nas unidades de terapia intensiva neonatais (UTIN) e apresenta consequências a curto e longo prazo. Esta lesão pode resultar em sequelas tanto de ordem estética quanto funcional, limitar o uso da VNI em RN que necessita desse suporte ventilatório, causar desconforto e septicemia; podendo aumentar, desta forma, o tempo de internamento na UTIN. Esta pesquisa tem por objetivo avaliar tecnológica e clinicamente os protetores nasais empregados na VNI de RN internados na UTIN. A metodologia consistiu primeiramente em levantar as possíveis causas da lesão nasal e avaliar os fatores de risco associados ao seu desenvolvimento. Em seguida, foi realizado um ensaio clínico randomizado para comparar os efeitos de três tipos de proteção nasal e das prongas novas e esterilizadas sobre a gravidade da lesão nasal. E por fim, foi realizada a caracterização térmica e estrutural dos protetores nasais após serem envelhecidas com temperatura e umidade no interior da incubadora neonatal. As principais causas da lesão foram relacionadas às características do material, a problemas no equipamento, a fatores assistenciais, neonatais e profissionais. Neste estudo, foram constatados como fatores de risco: a idade gestacional, a massa ao nascer, o tempo total de permanência na VNI, a reutilização deste suporte, o tempo da primeira utilização e da reutilização da VNI, bem como o tempo de internação na UTIN. Não foram observadas diferenças significativas na gravidade da lesão quando comparadas as três proteções estudadas, nem quando utilizadas prongas novas e esterilizadas. Quanto à análise dos materiais, foi constatado que a exposição à temperatura e à umidade alterou a percentagem de cristalinidade e a rugosidade das proteções nasais estudadas. / The nasal injury resulting from the use of non-invasive ventilation (NIV) is an adverse event increasingly common in the newborn intensive care unit (NICU) and shows the short and long term consequences. This lesion can result both aesthetic and functional sequelae, limit the use of NIV in newborns who need this ventilatory support, cause discomfort and septicemia, may thereby increase the length of stay in NICU. This research aims to evaluate technological and clinically nasal protectors used with NIV of newborns admitted to the NICU. The methodology consisted primarily in raising the possible causes of nasal injury and assess the risk factors associated with its development. Then, it was conducted a randomized clinical trial to compare the effects of three kind of nasal protector and new and sterilized prongs on the severity of nasal lesions. And finally, it was performed the thermal and structural characterization of nasal protection after being aged with temperature and humidity inside the neonatal incubator. The main causes of injury were related to characteristics of the material, equipment problems, assistive, neonatal and professional factors. In this study, it was found as risk factors: gestational age, weight at birth, the total time stay in the NIV, the reuse of this support, the time of first use and reuse of NIV and the length of stay in the NICU. They were not observed significant differences in lesion severity when compared the three protectors studied, nor when used new and sterilized prongs. The materials analysis indicated that exposure to temperature and humidity changed the percentage of crystallinity and the roughness of the nasal protections studied.