The attempt to identify risk factors or correlates of intraventricular hemorrhage (IVH) has been constrained by conflicting research findings, changing hypotheses about the etiology of IVH, and by the exceedingly complex nature of this neurological disorder. In addition, few studies have investigated the possibility that antenatal factors might predispose the infant to IVH. Thus, research aimed at identifying IVH correlates from all time periods in which stress could occur to the neonate needs to be undertaken. This study was conducted for the purpose of identifying and quantifying correlates of IVH by constructing an interactive statistical model to predict the occurrence, severity, and onset of IVH. The study sample was composed of inborn neonates admitted to the University of Utah Medical Center's Neonatal Intensive Care Unit from July 1985 to June 1987. Ultrasound brain scans were used to assigned 150 infants into two groups of equal numbers: an IVH group and a nonIVH group. Forty-three maternal, 17 obstetric, and 35 neonatal variables were collected from the infants' and infants' mothers' medical records and included demographic, medical, and behavioral data. The mean birthweights and gestational ages for the IVH and non-IVH groups were 1413 g, 29.9 weeks, and 1573 g 31.3 weeks, respectively. Factors found to be associated with IVH were neonatal hypotension, bronchopulmonary dysplasia, lower hematocrit percent, pulmonary interstitial emphysema, severe respiratory distress syndrome, shorter gestational ages, lower 5-minute Apgar score, pneumothorax, shorter umbilical cord lengths, and lower maternal hemoglobin concentrations. No obstetric factors were found to be related to IVH. A second-order, interactive model used to predict IVH occurrence and severity explained 90.9% of the total variability. The attempt to predict the onset time of IVH was unsuccessful. While the condition of the neonate immediately following birth is the best predictor of IVH, maternal or antenatal factors may interact to contribute to the development of this neurological disorder.

It is well documented in the literature that low-birth-weight (LBW) and prematurity are associated with a variety of developmental disabilities. Within this population of LBW children it is estimated that at birth, up to 45% of them experience intraventricular hemorrhage (IVH). Only recently has pediatric research begun to look at the potentially unique effects of IVH, and attempt to separate these out form the effects of LBW in general. The purpose of this study was to investigate the neuropsychological differences that may occur in children with a history of mild or sever IVH, who are now approaching school age. The main objective was to determine whether children, ages 4 and 5, who were diagnosed with a mild IVH at birth would perform differently on a neuropsychological screening from children who were diagnosed with a severe IVH. Twenty-nine 4- and 5-year-olds born at the University of Utah Medical Center and Primary Children's Medical Center constituted the sample for this study. Potential children were identified through the medical records, where documentation of incident and severity of IVH was obtained. Descriptive medical data and documentation of other common sequelae of LBW was also obtained from the medical records. Parents of potential subjects were contacted from the respective medical centers, and interested parents were then contacted by the research team and included in the study. The children were tested on a variety of neuropsychological functions by trained examiners from the Early Intervention Research Institute at Utah State University and from the Neuropsychological Consultation Services in Salt Lake City, Utah. Analysis of this data was used in determining whether or not there were residual differences in the performance of preschool-age children who have a history of IVH at birth. The results did not indicate significant difference between mild and severe IVH groups in performance on the neuropsychological assessment. Discriminant analysis showed no significant results which did not indicate that group membership could be predicted based upon test performance. Individual subtest analyses also did not indicate a significant difference in performance. Further analysis indicated significant relationships between the presence of other common sequelae of LBW/IVH such as seizure disorder and birth asphyxia, and the neuropsychological test results. Further research is needed to determine the reliability of these findings.

Technological advances in neonatal care have dramatically improved the survival and disability rates among low birthweight infants (LBW). One common factor associated with later problems among these babies is intraventricular hemorrhage (IVH). A meta-analysis was conducted among LBW infants with and without IVH to determine developmental outcome. More than 450 studies were located. Only 125 studies met inclusion criteria. Mean effect sizes were computed by comparing the LBW group to either a fullterm children, LBW children scored worse in all areas except gross motor skills. Cognitive assessment was done commonly up to 6 years of age. LBW infants scored about 1/2 standard deviation below their comparison group. A positive linear trend was found for severity of IVH: those children without an IVH scored comparably to fullterm children, while those with severe bleeds were about one standard deviation behind. Assessment of academic skills was done with the 8- to 11-year olds. There was no information given on presence/severity of IVH. Very few assessments were done. On general academic measures, the LBW children scored about 1/2 standard deviation behind the comparison group. Over 80% of the language assessments were done at 15- to 38-months of age. LBW children tended to score 1/2 to 3/4 of a standard deviation below the comparison group. The severity of hemorrhage did not mediate these results. Fine motor assessments were performed on children 9 months to 11 years old. LBW children were about 2/3 of a standard deviation behind the comparison group. These skills were not affected by severity of IVH. Gross motor abilities were typically measured before the children were 24 months old. LBW children showed more deficits in this area than in any other: almost 90% of a standard deviation behind. Gross motor skills appear to be strongly impacted both by being low birthweight and by the severity of IVH. Results indicate that IVH is a mediating factor in outcome among LBW infants. More research needs to be conducted on these children when they are school age, so long-term effects of low birthweight can be determined.

Subarachnoid hemorrhage (SAH) comprises 7% of all stroke cases, and is associated with a disproportionately high morbidity and mortality with few therapeutic options available. The goal of this project was to understand the mechanism of neurological deterioration after experimental SAH, with a focus on cerebral vasospasm and brain injury after SAH. We tested the hypothesis that endothelial nitric oxide synthase (eNOS) is upregulated and uncoupled after SA, resulting in exacerbated neurological injury in a mouse model of SAH. The project entailed the investigation of eNOS-dimer uncoupling, its association with oxidative and nitrosative stress in the brain parenchyma and finally its association with secondary complications after SAH. In our studies we demonstrated the crucial role eNOS plays in anti-microthromboembolism, anti-apoptosis and maintenance of physiological superoxide (O2-)/NO balance. This study suggests that SAH up-regulates and disrupts eNOS, producing peroxynitrite (OONO-) and other radicals that further exacerbate the oxidative insult and neurological injury.

Subarachnoid hemorrhage (SAH) comprises 7% of all stroke cases, and is associated with a disproportionately high morbidity and mortality with few therapeutic options available. The goal of this project was to understand the mechanism of neurological deterioration after experimental SAH, with a focus on cerebral vasospasm and brain injury after SAH. We tested the hypothesis that endothelial nitric oxide synthase (eNOS) is upregulated and uncoupled after SA, resulting in exacerbated neurological injury in a mouse model of SAH. The project entailed the investigation of eNOS-dimer uncoupling, its association with oxidative and nitrosative stress in the brain parenchyma and finally its association with secondary complications after SAH. In our studies we demonstrated the crucial role eNOS plays in anti-microthromboembolism, anti-apoptosis and maintenance of physiological superoxide (O2-)/NO balance. This study suggests that SAH up-regulates and disrupts eNOS, producing peroxynitrite (OONO-) and other radicals that further exacerbate the oxidative insult and neurological injury.

No description available.

Hemoglobin is an oxygen binding protein in erythrocytes. Hemoglobin is composed of four polypeptide chains. During the fetal stage the type of hemoglobin called fetal hemoglobin (HbF) dominates. After birth HbF is replaced by adult hemoglobin (HbA). HbF persists in concentrations less than 1%. Elevated concentration of HbF in adults exists in different conditions, Talassemi for example. When the uterus is damaged and the fetus doesn’t feel well its blood can pass the placenta barrier and enter the blood stream of the mother. A venous blood sample from the mother is analyzed to determine the status of the fetus. Laboratory Medicine Västernorrland already has two methods for analyzing HbF, one routine and one on call. The routine method needed to be replaced and the possibility to use flow cytometry was investigated. In this study, results from flow cytometry using Fetal Cell Count™ kit was compared to the results from the presently used methods, Kleihauer-Betke and HPLC. Cord blood was diluted with venous blood from an adult with the same blood group in various concentrations. A number of tests were performed and showed a fairly good correlation between the different methods. However more tests will be necessary to draw any clear conclusion.

Analytical methods used clinically in Sweden for detection and quantification of fetal hemoglobin (HbF) in maternal blood are either the microscopic method Kleinhauer Betkes test (KBT) or high performance liquid chromatography. A more modern alternative to detect and quantify HbF+ erythrocytes is flow cytometry. The aim of this project was therefore to evaluate the commercial kit "Fetal Cell Count kit" using flow cytometry. The kit used two antibodies; one directed against the specific γ-chain of HbF protein and the other directed against the intracellular enzyme carbanhydrase (CA), which is found in all erythrocytes in adults. The resulting data showed good precision, sensitivity and linearity. A reference interval based on male blood donors was determined to <0.1 % HbF+ erythrocytes and <1.3 %F-cells. The kit is well suited to detect and quantify F-cells. It could be used as a important tool to follow-up patients withβ-thalassemia and sickle cell anemia. However the kit was not as useful for detection and quantification of HbF+ erytrocytes in fetomaternal hemorrhage induced by Rhimmunization.

Cerebral vasospasm following subarachnoid hemorrhage has high morbidity and mortality. Mathematical modeling of the progression of the condition provides insight to improve clinical treatment of patients post subarachnoid hemorrhage. An existing model of the clotting cascade is expanded to include the theoretical conditions of cerebral vasospasm. We consider clotting factor XIIIa, which has been implicated as a primary cause of the entrenchment of the smaller diameter. Solutions for clotting are used as boundary conditions to solve the concentration of diffusible clotting factors in the vessel wall and cerebrospinal fluid (CSF). Each domain (clot, vessel wall, CSF) is described by a separate initial-boundary value problem, requiring unique conditions, reaction-diffusion equations, and diffusion coefficients. Additionally, the results from the first domain (the clot) provide a subset of the boundary conditions for the second and third domains (arterial wall and CSF, respectively). Although this approach captures many detailed components of the clotting process, a simpler method for investigating the formation and dissolution of a clot post subarachnoid hemorrhage is to neglect the bulk of the clot cascade to focus on the most salient features, namely, the formation of cross-linked fibrin and the degradation of fibrin by plasmin. By assuming first order kinetics in the initial hours following hemorrhage, we find a simplified expression with kinetic rates that may be adjusted depending on experimental conditions.

published_or_final_version / abstract / toc / Surgery / Doctoral / Doctor of Philosophy