Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

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

Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Feb. 19, 2009). Includes bibliographical references.

Thesis (MSc)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: Hypertensive conditions of pregnancy, such as pre-eclampsia, are the principal direct cause of maternal morbidity and mortality and affect up to 10% of first pregnancies worldwide. The placenta is vital in the pathogenesis of pre-eclampsia since the condition only occurs in the presence of placental tissue and the only cure is delivery of the placenta and the fetus. It has been hypothesised that the placenta may be the source of a circulating factor(s), which transports freely in the maternal system, resulting in the multi-systemic and immunological responses that are characteristic of pre-eclampsia. Among the potential "circulating" candidates currently being investigated worldwide, is the tachykinin member, neurokinin B (NKB). The aim of this project was to use a novel approach and investigate the role of Neurokinin B in pre-eclampsia on a genetic level. This would be achieved by bioinformatie characterisation of the neurokinin B (TAC3) and neurokinin B receptor (TACR3) genes. Samples from thirty pre-eclampsia patients (of whom 10 also had abruptio placentae) and twenty control individuals were used for mutation detection analysis involving Multiphor gel electrophoresis and automated sequencing. Three sequence variants were identified in the TAC3 gene and include: (i) 5' UTR variant (-25 c-t); (ii) intronic variant IVS3-53 (t-g) and (iii) 3' UTR variant exon 7 (479, t-c). Only the -25 c-t variant had been reported before (SNP database). A further two variants were identified in the TACR3 gene: (i) exon 3 variant (nt 857, a-t) and (ii) 3' UTR variant, amplicon 5b (nt 1471, t-c), of which the latter had previously been reported in the SNP database. In the analysis of allele and genotype frequencies, only variant homozygosity for TAC3 -25 c-t could be associated with increased risk of pre-eclampsia (RR 3.33, p=0.03). Follow-up work will include extended genotyping in further stratified and larger patient cohorts and transfection studies to assess splicing potential and functional consequences of the mutant alleles. These data represent the first documented mutation screen of the TAC3 and TACR3 genes and report novel variants in patients with pre-eclampsia. This study contributes to the knowledge of neurokinin B as a circulatory molecule and confirms the heterogeneity of pre-eclampsia. / AFRIKAANSE OPSOMMING: Die belangrikste direkte oorsaak van moedersterftes is hipertensiewe toestande in swangerskap, insluitende pre-eklampsie. Hierdie toestande kompliseer wêreldwyd 10% van alle swangerskappe. Die plasenta is kardinaal in die ontwikkeling van die siekte aangesien dit slegs voorkom terwyl die plasenta in-situ is en die simptome opklaar na verlossing van die plasenta. 'n Moontlike hipotese is dat die plasenta 'n sirkulerende agens afskei wat in die moederlike sisteem beland en die uiteenlopende multi-sistemiese simptome en tekens van die siekte veroorsaak, asook aktivering van die immuunsisteem. Een van die moontlike kandidate wat tans wêreldwyd ondersoek word as moontlike sirkulerende agens, is Neurokinien B (NKB), 'n lid van die Tachikinien familie. Die unieke benadering van hierdie projek was om die rol van Neurokinien B in pre-eklampsie te ondersoek op 'n genetiese grondslag. Dit is bereik deur bio-informatiewe karakterisering van die neurokinien B (TAC3) en neurokinien B reseptor (TACR3) en deur mutasie sifting op DNA monsters van 30 pasiënte met pre-eklampsie (waarvan 10 ook abruptio placentae gehad het) en twintig kontrole individue met behulp van Multiphor gel elektroforese en ge-outomatiseerde volgorde bepaling. Drie volgorde variasies is geïdentifiseer in die TAC3 geen en sluit in: (i) 5' UTR variant (-25 c-t); (ii) introniese variant IVS3-53 (t-g) en (iii) 3' UTR variant in ekson 7 (479, t-e). Slegs die -25 c-t variasie is voorheen raporteer (SNP databasis). Nog twee variante is ook gevind in die TACR3 geen: (i) ekson 3 variant (nt 857, a-t) en (ii) 3' UTR variant, amplikon 5b (nt 1471, t-e); hierdie laaste een is al in die SNP databasis raporteer. In 'n analise van genotipe en allele frekwensies is slegs homosigositeit vir variant TAC3 -25 c-t geassosieër met 'n verhoogde risiko vir preeklampsie (RR 3.33, p=0.03). Verdere werk sal nou fokus op die genotipering van groter en gestratifiseerde pasiënt kohorte en transfeksie studies om splitsing potensiaal en funksionele gevolge van mutante allele te ondersoek. Hierdie data is die eerste gedokumenteerde mutasie sifting van die TAC3 en TACR3 gene en verslag word gelewer van unieke variasies in pasiënte met pre-eklampsie.

Thesis (MA)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: The objective of this thesis is to review and synthesize the scientific literature on cognitive and neuropsychological deficits associated with children who were exposed to alcohol prenatally and to highlight possible areas of future attention. High incidences of Fetal Alcohol Syndrome has been reported especially in patients from low socio-economic areas. The highest reported incidence is found in the Western Cape province in South Africa. The devastating part of FAS is that its affects are entirely preventable. Alcohol is a physical and a behavioural teratogen. Prenatal alcohol exposure causes structural damage to the central nervous system and the brain that is vulnerable throughout the pregnancy. A dose-response association exist as exposure to heavier amounts of alcohol can cause more harm. The timing and pattern of alcohol consumption also plays a role. To date though, no "safe" level of alcohol consumption during pregnancy can be advocated. Various neuropsychological decrements are found in individuals with fetal alcohol syndrome or alcohol related neuro-developmental deficits as evaluated on standardized tests. Mental retardation is commonly found and even individuals with normal IQ's still display other learning disabilities. IQ's remain stable over the life span. Along with impaired intellectual functioning they also struggle with mathematical tasks especially as their complexity increases. Speech and language development is also delayed in individuals with FAS. There is little variation in the pith and display poor language comprehension. Attentional deficits are also noted and especially impact on academic functioning. Clinically, children often present with ADHD but in-depth studies have revealed that neurobiologically there is some differences as children with FAS struggle more with encoding and shifting of attention as opposed to other patients with ADHD. Difficulties with visual-spatial functioning has also been found. Verbal learning and memory are also impaired in individuals with FAS. Their poor verbal learning are influenced by their shallow level of encoding. Problems with fine motor skills are also noted. It also appear that all executive functions are impaired. They demonstrate poor planning skills, initiation, cognitive shifting, slow information processing, their thinking is concrete and they have poor self-regulatory skills. Behavioural problems include impulsivity, hyperactivity, aggressiveness, poor social skills and impaired judgement. Early intervention is thus essential to lessen the impact of neuro-psychological deficits on functional adaptation. A sensitive battery of neuro-psychological tests are also required to identify all the impairments in affected individuals and to plan more focussed intervention strategies. / AFRIKAANSE OPSOMMING: In hierdie tesis word 'n oorsig aangebied van literatuur wat betrekking het op die disfunksie van kinders wie se moeders tydens swangerskap alkohol misbruik het. Leemtes asook moontlike areas van toekomstige navorsing, is bespreek. 'n Hoe voorkoms van fetale alkohol sindroom (FAS) word gerapporteer, pasiente uit die lae SES gebiede. Die hoogste voorkoms word gerapporteer in die Wes- Kaapse provinsie in Suid Afrika. Wat die probleem meer tragies maak, is die feit dat dit heeltemal voorkombaar is. Alkohol is 'n teratogeen wat fisieke, neurologiese en gedragsimplikasies het. Blootstelling aan alkohol voor geboorte veroorsaak strukturele veranderinge in die sentrale senuweestelsel en die brein. Blootstelling tot hoer volumes van alkohol veroorsaak noodwendig meer skade. Die spesifieke stadium van alkohol-inname tydens die swangerskap, en die moeder se drinkpatroon, speel 'n rol in die neurosielkundige uitkomste. Tot op hede kon geen veilige alkoholsvlak tydens swangerskap vasgestel word nie. Verskeie neurosielkundige uitvalle is gevind in kinders met FAS en ook kinders met alkohol-verwante neurologies ontwikkelings probleme, volgens neurosielkundige toetsing. Verstandelike gestremdheid kom algemeen voor in kinders met FAS. Kinders met FAS wat oor normale intellektuele vernoens beskik ervaar leerprobleme. Die intellektuele inkortings bly stabiel oor die lewenspan. Kinders met FAS ondervind erge probleme met wiskunde, veral wanneer die werk moeiliker raak. Die spraak-en taalontwikkeling wat kinders met FAS ervaar sluit in beperkte taalbegrip en intonasie. Hulle kort aandagspan affekteer veral hulle akademiese funksionering. Die aandagsteuring van kinders met FAS en kinders met aandagstekort-hiperaktiwiteit versteuring verskil neuro-biologies. Verdere verskille bestaan ook aangesien kinders met FAS spesifiek sukkel met swak enkoderingsvermoe en om kognitiewe aanpassings te maak. Visueel-ruimtelike verrnoe van kinders met FAS is ook benadeel. Hulle sukkel ook met verbale leer en hulle geheue is ook ingekort. Die inkortings dui op 'n oppervlakkige enkoderingsvermoe. Probleme met fyn-motoriese vaardighede is ook gevind, volgens toetseing. Toetse wat gemik is om uitvoerende funksies te evalueer, het verskeie uitvalle aan die lig gebring. Probleme in abstrakte redenering, beplanning, impulsiwiteit, self-regulering, en die lnlslerlnq en prosessering van informasie. Gedragsprobleme soos swak sosialiseringsvaardighede, aggresiwiteit, swak oordeel en hiperaktiwiteit. Die wye neurosielkundige uitvalle wat voorkom in kinders met FAS noodsaak vroee intervensie om die langtermyn-impak daarvan te verminder. Hiervoor word 'n sensitiewe battery neurosielkundige toetse benodig wat al die kognitiewe uitvalle kan identifiseer.

Increasing adverse birth outcome are a major concern in South African maternal care and globally In South Africa, perinatal mortality rate of 40/1000 and maternal mortality ratio of 150/100 000 are poor considering the fact that 95.1 percent of women attend antenatal care and 83.7 percent of women deliver in a medical facility. This study focuses on the effect of lack of adequate antenatal care on adverse birth outcome using data from the 1998 South African Demographic and Health Survey. The analysis is based on univariate and bivariate analysis to examine the effect of socio- demographic characteristics on adverse birth outcomes. In addition, binary logistic regression is used to examine the impact of antenatal and sociodemographic characteristics on adverse birth outcome. The results show majority of women reporting adverse birth outcome are those who delivered though caesarean section (53 percent) and that most of these women are likely to be educated and have better socio economic status and that they are likely to be Non African. It is also shows that the proportion of women attending antenatal care adequately is very high in South Africa. The results show that the use of antenatal care is determined by a range of socio demographic factors including the level of education and the economic status of the mother. Only timing of antenatal care, place of delivery and race had a significant effect on adverse birth outcome. All other variables were not significant. Results from the binary regression analysis show that women who started their antenatal care during second and third trimester (95%CI: 0.211-0.975), were Non African (95%CI: 1.082 to 2.098) and delivered in a private health facilities (95%CI: 0.28 to 0.73) were more likely to have adverse birth outcome compared to their counterparts. Most women choosing caesarean section do so without adequate information on the disadvantages of delivering through caesarean section. Therefore, there is a need to focus maternal health education to all women in South Africa regardless of their socio- economic status background / Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2007.

Placental dysfunction is implicated in the pathogenesis of preeclampsia. Chemical signals between the placenta and maternal circulation are a suspect cause of endothelial dysfunction and maternal hypertension. This study examined select lipid mediators of inflammation produced by the placenta. Patients were recruited from Virginia Commonwealth University’s pregnancy clinics and placentas were collected at delivery. Forty-eight-hour explant cultures of villous placental tissue were used to model lipid production. Electrospray ionization mass spectrometry was used to quantify concentrations of free lipids in the culture media. Bicinchoninic acid assays were performed to quantify protein in each culture for normalization of lipid data. After analysis, it was found that severity of preeclampsia was correlated with a unique lipid profile. Pro-inflammatory hydroxyeicosatetraenoic acids and sphingolipids were elevated. Aspirin usage in patients who developed preeclampsia was found to attenuate accumulation of isoprostane oxidative stress markers and thromboxane production while preserving omega-3-fatty acid and increasing prostacyclin levels.

Includes list of papers arising from this thesis. "July 2004" Includes bibliographical references (leaves 253-297)

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 70-78).

No description available.