Magister Chirurgiae Dentium (MChD) / There is an absence of both dental services and systematic planning to meet the oral health needs of the Black* population ~f greater Cape Town. Little epidemiological data exists upon which such planning can be based. This study describes the prevalence and treatment need related to tooth decay and periodontal disease ofaXhosa-speaking* squatter community on the outskirts of Cape Town. An age and sex stratified sample of 290 adults attending the SACLA clinic in Crossroads were examined. Examiner variability was measured by a percentage intra-examiner agreement for the DMFT of 95% and for the CPITN 84%. Cohen's kappa statistic, for tooth-specific caries detection errors was k = 0.877. The mean DMFT was 11.8 and varied little with sex or age below 55 years. After this age, the DMFT climbs steeply due largely to the rapid increase in the M value (missing teeth). The results show that for every tooth needing to be extracted, two teeth per subject required a restoration. Only three subjects already had some restorations. Periodontal health was reflected by a high prevalence of calculus (TN2 = 99%; MNS = 5.2) for the whole sample. Deep pockets were detected in 13% of those aged between 15 and 29 years, but only at a relatively low intensity (MNS = 0.1). This prevalence reached a high 60% for those aged between 45 and 64 years (MNS = 1.7). All subjects require oral hygiene instruction and gross scaling in at least four sextants, according to CPITN criteria. In conclus~on it is noted that there is a shortage of relevant epidemiological information necessary to the planning of oral health services to improve the oral health of the Xhosa-speaking community in the Western Cape. Caries prevalence rates are already high in young adults and a high tooth mortality rate and an absence of fillings, suggests that extraction is the only form of treatment made available to this community. The absence of appropriate prevention strategies such as water fluoridation is reflected in these results. The existence of small amounts of severe periodontal disease in young adults is of concern. The high prevalence of mild (and preventable) periodontal disease, seems to reflect a low awareness of the condition and/or a lack of resources to control it. It is no coincidence that such poor oral health was observed in this, a poor, peri-urban squatter community. This study, serves as a sad reminder of the maldistribution of oral health and socia-economic resources in South Africa. The socia-economic and political character of this community is reflected by the epidemiological picture of oral health observed in the study. It is clear that further data must be collected, especially a clear assessment of community-expressed needs. Active planning must take place urgently to integrate oral health with Primary Health Care to rectify the serious misuse and maldistribution of oral health resources required to improve the oral health of this population.

Acute and subacute diseases causing intrinsic spinal cord damage are confusing and poorly defined clinically and pathologically. of this study is: The purpose 1. To analyse the spectrum of conditions responsible for acute and subacute myelopathy in South Africa. 2. To categorise the clinical presentations and prognosis of the illnesses and to correlate these with aetiology. 3. To assess the validity of diagnostic criteria for acute and subacute myelopathy in general and for the different aetiological groups. 4. To review the literature and to correlate previous studies with the present one. Thirty-four patients fulfilling strict criteria nave been identified over a seven-and-a-half-year period using the Groote Schuur Hospital computer retrieval system. Although the study was essentially retrospective, 11 of these patients were seen personally during their acute illnesses. All these patients have suffered from illnesses causing spinal cord dysfunction in the absence of trauma, physical agents or any extrinsic pressure such as might be caused by tumours or spondylosis. Maximum disability was reached in less than 8 weeks. In 17 patients no cause was identified. The clinical features, laboratory findings and courses have been analysed. Among the results, a high percentage of patients with Brown-Sequard Syndromes were found with possible significance for the pathogenesis of the illness. Seven patients with meningovascular syphilis were analysed as well as 2 additional patients with spinal cord syphilis not fulfilling the strict criteria of the study. Although well known before the penicillin era, this entity is not well described in modern neurological literature. Four patients had myelopathy associated with pulmonary tuberculosis in the absence of tuberculous meningitis or spinal disease. Three of these 4 patients also developed optic neuropathy. The association of these conditions has previously been described in only a very few patients. Two patients had Epstein-Barr virus infections and 1 had an infection with Mycoplasma pneumoniae. Two had systemic lupus erythematosus and 1 had an acute cord infarct following an aortic aneurysm repair. The literature is reviewed and the findings of this study correlated with previous ones. Conclusions regarding terminology, criteria for diagnosis, investigations, course and prognosis are discussed.

This thesis is about the politics and the possibilities of aetiology. Firstly, the possibilities. Does an infectious disease have one, single pathogenic cause or many, interacting causes? In the medical microbiological sciences, there is no definitive answer, one way or another, to this question: there, the conditions of aetiological possibility exist in a curious tension. Ever since the birth of the 'germ theory of disease' and the concomitant birth of the singular aetiological object, these conditions have allowed for the co-existence of a very different, and far less well understood kind of object: the multifactorial object. That SARS was caused by one, singular viral agent, a coronavirus (CoV), is now entrenched as microbiological fact. And yet, the curious thing about SARS is that the history of the 2003 outbreak is littered with moments at which the possibility of the multifactorial object presented itself to, and was actively considered by, medical microbiologists. So how did we get here - to SARS-CoV, an infectious disease that could be understood and storied in this, the most singular of ways? And what happened along the way to deny the multifactorial aetiological object any kind of existence at all? In an attempt to grapple with these questions, the thesis seeks to recover the possibility of the multifactorial object through a deep, ethnomethodological reading of the moments at which it flared up precise/y as a possibility for medical microbiologists investigating the outbreak. What emerges from that recovery operation is a sense that the multifactorial object was never actually ruled out or disproved in any way, but rather, was vanished. Put another way, the suggestion is that various medical microbiological practices and interventions, whilst establishing singularity, were serving, at the same time, to create an illusion of multifactorality's non-existence; an illusion behind which the issue of multifactorality, its possibility, could be discarded without ever having to be resolved, one way or the other. In the closing sections of this thesis a move is made towards suggesting that SARS-Co V, the singular disease, was the product of a choice-, a choice that was made to explore one aetiological possibility at the expense of another. And that is where the politics comes in. For if politics, the realm of the political, can be taken to arise in situations where various possibilities exist but not all possibilities can be chosen, then it follows that what this thesis provides is an opportunity to foreground the politics bound up with the practical doing of aetiology. As a result, and based on the experience of attempting to recover the vanished multifactorial object from the 2003 SARS outbreak, the thesis concludes with an attempt to inhabit the present in such a way as to make it possible to think, in a little more detail, about where aetiology, as understood by medical microbiologists, might be heading in the future: might recent shifts in practical, everyday, seemingly innocuous microbiological technique, have begun to make it easier to coax the multifactorial object out into a space of visibility? Might those shifts actually herald the crossing of an epistemological threshold in the medical sciences? And might the conditions of aetiological possibility be changing, and changing in ways that would drastically alter what it meant to speak of a 'disease', an 'infection' and a 'pathogen'?

Background Among adolescents and young adults with DSM-IV alcohol use disorders (AUDs), there are inter-individual differences in the speed of transition from initial alcohol use (AU) to AUD. AUDs are highly co-morbid with other mental disorders. The factors associated with rapid transition from first AU to AUD remain unknown and the role of mental disorders in rapid transitions is unclear. Given this background we examined (1) whether prior anxiety, mood, externalizing and non-alcohol substance use disorders are related to the risk and speed of transition from first AU to DSM-IV alcohol abuse (AA) and alcohol dependence (AD) and (2) whether early age of onset of prior mental disorders (PMDs) is a promoter of rapid transition. Method A total of 3021 community subjects (97.7% lifetime AU) aged 14–24 years at baseline were followed up prospectively for up to 10 years. AU and mental disorders were assessed with the DSM-IV/M-CIDI. Results Among subjects with lifetime AU, several PMDs, such as specific phobia, bipolar disorder and nicotine dependence, were associated with an increased risk of AUD independent of externalizing disorders. Associations of PMDs with the speed of transition to AUDs were mostly weak and inconsistent. Only social phobia and externalizing disorders were associated with faster transitions to AD even after adjustment for other PMDs. Earlier age of onset of PMD was not associated with rapid transition. Conclusions Mental disorders are associated with the risk of AUD. With the possible exception of social phobia and externalizing disorders, they do not promote rapid transition, even if they occur particularly early. Future research needs to identify factors relevant to rapid transition to AUD.

No abstract available. / Thesis (M.D.)-University of Natal, 1973.

Excessive weight can have a severe impact on health as well as creating a significant economic burden. Obesity is reaching epidemic proportions, but the mode of inheritance of obesity and its underlying complexity remains largely unresolved. Thus, the aim of this research project was to provide a further understanding of this condition in an Australian adolescent and adult population. Qualitative and quantitative differences in genetic and environmental influences affecting body mass index (BMI) in males and females, during development were examined. Structural equation models were fitted to longitudinal data collected at ages twelve, fourteen and sixteen from 470 monozygotic (MZ) twin pairs and 673 dizygotic (DZ) twin pairs. In addition, it is generally known that some genetic differences are only exposed in the presence of certain environmental stressors, such as the effects of parity and age on post-partum obesity. Therefore, models were fitted to data from 11, 915 female twins and their sisters from whom reproductive history was available in order to assess the changes in magnitude of genetic and environmental variation in female BMI due to these variables. To detect quantitative trait loci (QTLs) influencing adolescent BMI, up to 1133 highly polymorphic microsatellite markers were typed across the genome in a sub-sample of adolescent twins, their parents and siblings. Because gene mutations for some genetic disorders affecting body weight may manifest during childhood, univariate linkage analysis were applied to test for linkage between marker loci and BMI at twelve, fourteen and sixteen across the genome. Additionally, genes involved in pathways regulating body weight may operate differently in men and women. Therefore, a genome-wide linkage analysis allowing for sex difference in linkage patterns was performed in order to identify QTLs influencing BMI which may differ between adult males and females. Genetic factors contributed strongly to BMI in adolescent twins, accounting for approximately ninety percent of phenotypic variation at twelve, fourteen and sixteen years of age. In addition, the majority of this genetic variance was transmitted from age twelve to ages fourteen and sixteen. Sex differences in the size of genetic innovations at ages fourteen and sixteen suggest that the genetic variation in weight regulation is different in males and females. The presence of environmental influences in males and females may reflect the effects of lifestyle activities during adolescents such as severe exercise and diet regimes. Structural equation models exploring the effects of parity and age on female BMI revealed that genes become more important in the variation in BMI as parity increases. The ability to retain weight for lactation and support for foetal growth possibly reflects an evolutionary advantage in times when it was a necessary condition of survival. Unique environmental influences were also important in the variation female BMI across parity and age, possibly reflecting lifestyle factors and individual responses to social attitudes towards weight gain. Genome-wide linkage analysis in adolescent twins revealed strong evidence for linkage on chromosome 14q12-q13 at age fourteen (logarithm of odds (LOD) = 3.71, p = 0.000018) and suggestive linkage in the same region in sixteen year old twins (LOD = 2.46, p = 0.00038) which has been previously implicated in adiponectin in Northern Europeans. Chromosome 6p12 yielded a suggestive LOD = 2.95 (p = 0.00012) which harboured a known gene responsible for rebound weight gain. Evidence for replication (LOD = 1) at other areas of the genome was also observed, including 1, 4, 10, 11, 13 and 20, which have been previously associated with obesity in other studies, being LEPR, UCP1, OB10P, BMIQ3 and BMIQ6, respectively, although we did not have time to genotype these to test for association in our samples. The use of a genome-wide linkage analysis allowing for sex difference in linkage patterns identified areas on chromosome 8 and 20, providing us with evidence that some of the genes responsible for BMI may have different effects in adult men and women. Results revealed a suggestive linkage peak (-log10p = 3.13; equivalent to LOD = 2.19, p = 0.000741) at 12q24 (-log10p = 3.02; equivalent to LOD = 2.08, p = 0.000955), that has been implicated in weight in a wide range of populations and where non-insulin-dependent diabetes mellitus, a consequence of obesity, has also been mapped. We also identified many peaks near the threshold for replicating an existing finding (-log10p = 2; equivalent to LOD = 1.18, p = 0.01) in many areas across the genome that are within regions previously identified by other studies, as well as in locations that harbour genes known to influence weight regulation. Finally, the significances of these results are discussed and future directions are considered including association analysis on single nucleotide polymorphisms (SNPs) across six candidate genes: LEPR, GNβ3, UCP2, UCP3, FTO and INSIG2 which have previously been associated with obesity or BMI. We typed seventeen SNPs and performed analyses in a sample of 4494 MZ and DZ twins. Significant association was found for rs9939609 (A/T polymorphism) of the FTO gene. In our data, each additional copy of the rs9939609 A allele increased mean BMI by approximately 0.14kg/m2 in an apparent additive manner, comparable with recent published results from population-based studies in white European children and adults.

Abstract The objective of this study was to investigate intellectual disability (ID) in children, with focus on occurrence, associated biomedical and sociodemographic factors, probable psychiatric problems and temporal variations in the occurrence of ID and the associated factors in an interval of 20 years. The study population consisted of two birth cohorts of children born in northern Finland, the Northern Finland Birth Cohort 1986 (NFBC 1986, N = 9,432 live-born children) and the Northern Finland Birth Cohort 1966 (NFBC 1966, N = 12,058 live-born children). Temporal changes in ID were studied by comparing NFBC 1986 with NFBC 1966. The same definition of intellectual disability (intelligence quotient ≤70), time of follow-up (up to 11.5 years), case ascertainment methods and data sources were used. Data were collected from questionnaires, registers and records. In NFBC 1986 the incidence of ID was 12.62/1,000 by age 11.5 years and prevalence 11.23/1,000 live-born at age 11.5 years. Associated biomedical aetiology could be found in two thirds of the cases. Genetic disorders were the largest aetiological category (36.1%) associated with ID. Maternal disadvantage (unskilled worker, basic education only) had the largest impact on the incidence of ID, while among single independent factors, maternal prepregnancy obesity (body mass index ≥30) showed the highest risk for ID (OR 2.8, 95% CI 1.5, 5.3) in the offspring. According to the assessments by the teachers at school children with ID had 4.9 times more likely probable behavioural problems than their peers not having ID. In an interval of 20 years, there was no change in the incidence or in the prevalence of ID between NFBC 1986 and NFBC 1966. However, a shift occurred from more severe levels of ID towards mild ID, so that both the incidence and prevalence of mild ID increased by 50% whereas more severe ID decreased by 50%. Temporal changes appeared in the proportions of aetiological categories (NFBC 1986 vs. NFBC 1966) with a statistically significant decrease of Down syndrome and paranatally originating causes (traumas/asphyxia). The proportion of chromosomal disorders other than Down syndrome increased, as did malformations of the central nervous system. Among sociodemographic factors associated with ID, indicators of socio-economic disadvantage retained their status as having the largest impact on the incidence of ID. Over the 20 years, the mother being single, living in a remote area and mother's older age at time of delivery had lost their association with ID. Only one new maternal sociodemographic factor, prepregnancy obesity, had emerged as having an association with ID with a statistically significant difference between NFBC 1986 and NFBC 1966. In conclusion, these results indicate that although the occurrence of ID remained the same in northern Finland over a period of 20 years, temporal changes have taken place in the biomedical and sociodemographic factors contributing to the incidence and prevalence of ID. There are also factors that have retained their status as associated disadvantageous factors. Studies like this with repeatedly collected data in the same geographical area, describing the occurrence of ID, and analysing associated biomedical and sociodemographic factors, are valuable for evaluating developments in the health care and service system. They are also of value for future planning of services for individuals with ID. / Tiivistelmä Tämän tutkimuksen tavoitteena oli selvittää kehitysvammaisuuden esiintyvyyttä lapsilla, siihen liittyviä lääketieteellisiä etiologisia ja sosiodemografisia tekijöitä, mahdollisia psykiatrisia ongelmia sekä kehitysvammaisuuden esiintyvyydessä ja siihen liittyvissä tekijöissä tapahtuneita muutoksia 20 vuoden aikana. Tutkimusjoukko muodostui kahden syntymäkohortin lapsista, jotka olivat syntyneet Pohjois-Suomessa, Pohjois-Suomen syntymäkohortti 1986 (NFBC 1986, N = 9432 elävänä syntynyttä lasta) ja Pohjois-Suomen syntymäkohortti 1966 (NFBC 1966, N = 12058 elävänä syntynyttä lasta). Kehitysvammaisuudessa tapahtuneita ajallisia muutoksia tutkittiin vertaamalla Pohjois-Suomen syntymäkohortti 1986:ta Pohjois-Suomen syntymäkohortti 1966:een. Tutkimuksessa käytettiin samaa kehitysvammaisuuden määritelmää (älykkyysosamäärä ≤70, seuranta-aika 11.5 vuoteen saakka), tiedonkeruun menetelmiä ja tietolähteitä. Tiedot kerättiin kyselylomakkeista, rekistereistä ja asiakirjoista. Pohjois-Suomen syntymäkohortti 1986:ssa kehitysvammaisuuden ilmaantuvuus oli 12.62/1000 11.5 vuoden ikään mennessä ja vallitsevuus 11.23/1000 11.5 vuoden iässä. Kehitysvammaisuuteen liittyvä lääketieteellinen etiologia pystyttiin selvittämään kahdessa kolmasosassa tapauksia. Geneettiset häiriöt muodostivat suurimman etiologisen luokan (36.1%). äitiin liittyvillä epäedullisilla sosiaalisilla tekijöillä (kouluttamaton työntekijä, vain peruskoulutus) oli suurin vaikutus kehitysvammaisuuden ilmaantuvuuteen, kun taas yksittäisistä sosiodemografisista tekijöistä korkein riski (vaarasuhde 2.8, luottamusväli 1.5, 5.3) oli äidin lihavuudella (painoindeksi ≥30) raskauden alussa. Koulussa opettajien arvioiden mukaan kehitysvammaisilla lapsilla esiintyi mahdollisia käytöshäiriöitä 4.9 kertaa useammin kuin ei-kehitysvammaisilla lapsilla. 20 vuoden aikana Pohjois-Suomen syntymäkohorttien 1986 ja 1966 välillä ei ollut tapahtunut muutoksia kehitysvammaisuuden kokonaisilmaantuvuudessa eikä -vallitsevuudessa. Kuitenkin tuli esiin siirtymä vaikeammasta lievempään asteeseen siten, etta lievän kehitysvammaisuuden ilmaantuvuus ja vallitsevuus lisääntyivät noin 50%, kun taas vaikeamman väheni 50%. Lääketieteellisten etiologisten luokkien osuuksissa tuli esiin ajallisia muutoksia (Pohjois-Suomen syntymäkohortti 1986 vs. Pohjois-Suomen syntymäkohortti 1966) siten, että Downin syndrooman sekä syntymän aikaan ajoittuvan vamman ja hapenpuutteen osuudet vähenivät tilastollisesti merkitsevästi. Keskushermoston epämuodostumien sekä muiden kromosomihäiriöiden kuin Downin syndrooman osuudet kasvoivat. Kehitysvammaisuuteen liittyvistä sosiodemografisista tekijöistä sosioekonomisen huono-osaisuuden osoittimet säilyttivät asemansa suurimpana ryhmänä. 20 vuoden aikana äidin naimattomuus, asuminen syrjäseudulla sekä korkeampi ikä lapsen syntymän aikaan olivat menettäneet yhteytensä kehitysvammaisuuteen. Pohjois-Suomen syntymäkohortti 1986:n ja Pohjois-Suomen syntymäkohortti 1966:n välillä tuli esiin vain yksi uusi kehitysvammaisuuteen tilastollisesti merkitsevästi liittyvä sosiodemografinen tekijä, äidin lihavuus raskauden alussa. Yhteevetona voidaan todeta, etta vaikka kehitysvammaisuuden kokonaisesiintyvyys oli pysynyt samana Pohjois-Suomessa 20 vuoden aikana niin esiintyvyyteen liittyvät etiologiset ja sosiodemografiset tekijät olivat osittain muuttuneet. Tämänkaltaiset tutkimukset, joissa peräkkäisinä ajanjaksoina kerätään tietoja samalla maantieteellisellä alueella ja jotka kuvaavat kehitysvammaisuuden esiintyvyyttä sekä analysoivat siihen liittyviä lääketieteellisiä ja sosiodemografisia tekijoitä, ovat hyödyllisiä arvioitaessa terveydenhoidossa ja palvelujärjestelmässä tapahtunutta kehitystä. Niitä voidaan hyödyntää myös suunniteltaessa tulevaisuudessa palveluja kehitysvammaisille henkilöille.

Thesis (PhD )--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Parkinson’s disease (PD), a neurodegenerative movement disorder characterized by resting tremors, bradykinesia, postural instability and rigidity, is due to a selective loss of dopaminergic neurons in the substantia nigra. Non-motoric symptoms include autonomic, cognitive and psychiatric problems. PD has been suggested to result from environmental factors, genetic factors or a combination of the two. Evidence has mounted over the last 13 years supporting the involvement of a significant genetic component. Mutations in the parkin, PINK1, DJ-1, ATP13A2, SNCA, and LRRK2 genes have been conclusively associated with PD. The aim of the present study was to establish the first study on the genetic etiology of PD in South African patients. Patients from the various South African ethnic groups with predominantly early-onset PD and/or a positive family history were recruited. Varying numbers of study participants (ranging from 88-205) were used for the different sections of this study depending on their availability at the time of the experiments and the specific clinical criteria applied. Mutation screening was conducted using High-resolution melt (HRM) analysis, DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). HRM analysis and sequencing of the known PD genes identified the following mutations: parkin (T113fsX163), PINK1 (Y258X), and LRRK2 (G2019S and R1441C). Using haplotype analyses, the five South African LRRK2 G2019S-positive patients were found to share a common ancestor with other G2019S haplotype 1-associated families reported worldwide. Two commercially available MLPA kits, SALSA P051 and P052, were used to assess the study participants for exon dosage mutations. Exonic deletions and insertions in parkin were identified in five patients. In addition, a family with a whole-gene triplication mutation of SNCA was identified. This is the 4th family worldwide to have this specific mutation which leads to a severe phenotype with autonomic dysfunction and early-onset dementia. The CAESAR (CAndidatE Search And Rank) bioinformatic program was used to select novel candidate genes for PD. CAESAR produced a ranked list containing known PD causing genes as well as novel candidates. The MAPT and SNCAIP genes were selected from the list of ten highest scoring genes. HRM analysis identified novel sequence variants in both genes with unknown functional significance that warrants further study. A novel 16bp deletion (g.-6_+10del) in the promoter region of DJ-1 was identified in one PD patient. The functional significance of this variant was investigated using a Dual-Luciferase Reporter assay. The variant was found to significantly reduce luciferase activity in two separate cell lines, HEK293 and BE(2)-M17 neuroblastoma cells, both with and without oxidative stress (p<0.0001), and we proposed that the 16bp sequence might be important in transcriptional regulation of DJ-1. In addition, the activity of three transcription factors (AhR, ARNT and HIF- 1) with binding sites within the deletion sequence may be influenced by the variant. In conclusion, mutation screening resulted in the identification of mutations in six patients in parkin, six patients in LRRK2, one patient in PINK1 and one patient in SNCA. In addition, a number of novel sequence variants were identified with unknown functional significance. Investigating the genetic basis of PD in the unique South African ethnic groups has shown that the known PD associated genes play minor roles in causing the disease in this population which indicates the possible involvement of other as yet unidentified PD genes. Innovative bioinformatic and wet bench experimental strategies are therefore urgently needed to identify new candidate genes for PD. / AFRIKAANSE OPSOMMING: Parkinson se siekte (PS), ‘n neurodegeneratiewe bewegings-siekte, gekarakteriseer deur rustende spiersametrekkings, bradykinesia, posturale onstabiliteit en rigiditeit, onstaan as gevolg van geselekteerde verlies van dopaminergiese neurone in die substantia nigra. Nie-motoriese simptome sluit in outonome, kognitiewe en psigiatriese afwykings. Dit is voorgestel dat PS ontwikkel as gevolg van omgewings- en genetiese faktore of ‘n kombinasie van die twee. Daar was ‘n toename in bewyse vir die verantwoordelikheid van die genetiese komponent oor die afgelope 13 jaar. Mutasies in die parkin, PINK1, DJ-1, ATP13A2, SNCA, en LRRK2 gene word met PS geassosieer. Die doel van hierdie studie was om vir die eerste keer die genetiese etiologie van PS in Suid- Afrikaanse pasiënte te ondersoek. Pasiënte van die verskillende Suid-Afrikaanse etniese groepe, met hoofsaaklik vroeë-aanvang PS en/of ‘n positiewe familie-geskiedenis, was gebruik. Wisselende getalle van studie-deelnemers (van 88-205) was gebruik vir die verskillende dele van die studie, afhangende van hul beskikbaarheid op die tyd van die eksperimente en die spesifieke kliniese kriteria wat van toepassing was. Mutasie-analiese was uitgevoer deur middel van Hoëresolusie smelting (HRS)-analiese, DNS volgorde-bepaling en multipleks ligasie-afhanklike ‘probe’ amplifikasie (MLPA). HRS-analiese en DNS volgorde-bepaling van die bekende PS gene het die volgende mutasies deïdentifiseer: parkin (T113fsX163), PINK1 (Y258X), en LRRK2 (G2019S en R1441C). Haplotiepe-analiese het gevind dat vyf Suid-Afrikaanse LRRK2 G2019S patiente ‘n gemeenskaplike voorvader deel met ander wêreldwyd gerapporteerde LRRK2 haplotiepe 1- geassosieerde families. Twee kommersieel beskikbare MLPA ‘kits’, SALSA P051 en P052, was gebruik om die deelnemers te toets vir exon-dosis mutaties. Exon-delesies en invoegings in parkin was gevind in vyf patiente. ‘n Familie met ‘n volle geen triplikasie van SNCA was gevind. Dit is die 4de familie wêreldwyd wat die spesifieke mutasie het en dit lei tot ‘n erge fenotiepe met outonomiese afwykings en vroeë-aanvang dementia. Die ‘CAESAR (CAndidatE Search And Rank)’ bioinformatiese program was gebruik om nuwe kandidaat PS gene te selekteer. Die program het ‘n lys kandidaat gene, wat beide bekende geassosieerde en nuwe bevat, opgelewer. Die MAPT en SNCAIP gene was gekies uit tien gene met die hoogste tellings. HRS analiese het nuwe DNS volgorde variante in beide gene gevind. Die funksies van die variante is tans onbekend en moet verder ondersoek word. ‘n Onbekende 16bp delesie (g.-6_+10del) in die promotor area van DJ-1 was gevind in een PS patient. ‘n Dubbel-lusiferase rapporteerder eksperiment was uitgevoer om die funksie van die variant te ondersoek. Die variant het die lusiferase-aktiwiteit aansienlik verlaag in twee afsonderlike sel lyne, HEK293 en BE(2)-M17 neuroblastoma selle, met en sonder oksidatiewe spanning (p<0.0001). Dit was voorgestel dat die 16bp volgorde dalk belangrik kan wees vir transkripsionele regulasie van DJ-1. Die variant mag dalk ook die aktiwiteit van drie transkripsie faktore (AhR, ARNT and HIF-1) met bindings plekke in die delesie- volgorde, beïnvloed. Ter afsluiting, mutasie analiese het gelei tot die identifikasie van mutasies in ses patiente in parkin, ses patiente in LRRK2, een patient in PINK1 en een patient in SNCA. ‘n Aantal nuwe variante was gevind met ombekende funksies. Ondersoek van die genetiese basis van PS in die uniek Suid-Afrikaanse etniese groepe het gevind dat die bekende PS gene nie ‘n groot rol speel in die ontwikkeling van die siekte in die populasie nie. Dit is moontlik dat ander onbekende PS gene hier verantwoordelik is vir die siekte. Dit is dus belangrik om innoverende bioinformatiese en eksperimentele strategieë toe te pas om nuwe kandidaat-gene, vir PS, te identifiseer. / University of Stellenbosch / Agence Nationale de la Recherche, France / South African Medical Research Council / Doris Crossley Foundation

In der kontroversen Diskussion um die unklare Ätiologie der Appendizits wird oft eine Motilitätsstörungen angeführt. Die Interstitial cells of Cajal sind bedeutend für die Motilität und die Entstehung der Peristaltik im menschlichen Kolon. Bei einigen Motilitätsstörungen des Darmes wurde eine Rarifizierung dieser Zellen beobachtet. Die ICC wuden noch nie in der Appendix vermiformis beschrieben.In dieser Arbeit wurden erstmals die ICC in der Appendix mittels einer immunhistochemischen Färbung durch einen maus-monoklonalen Antikörper ( NCL- cKit) nachgewiesen sowie analysiert. Es konnten keine Subgruppen IC-SMP und IC-MP in der Appendix nachgewiesen werden. Die IC-LM zeigten sich reduziert im Vergleich zum Kolon. Die IC-CM konnten zahlreich und regelmäßig dargestellt werden. Eine unterschiedliche Verteilung bzw. Dichte der ICC in der normalen Appendix, der akut und chronisch entzündeten Appendizits konnte nicht nachgewiesen werden.Schlussfolgernd und in Übereinstimmung mit den Beobachtungen anderer Autoren besitzt die Appendix eine reduzierte Motilität und eine physiologische Koprosthase, die aber allein nicht zu einer Entzündung führt. Erst unter dem Einfluss der aus der Literatur bekannten Kofaktoren wird die Koprosthase verstärkt. Erst dies führt zu einer Alteration der Schleimhaut und zur Appendizitis. / The aetiology of the childlike appendicitis is not generally known, but a motility disorder is discussed. The Interstitial cells of Cajal (ICC) are important for the motility and the development of the peristalsis of the colon. In some motility disorders the ICC are abnormaly distributed. The ICC of the human vermiform appendix has never been examined before. We proved and analysed the ICC of the appendix with the mous-monoclonal antibody against c-kit, (NCL-cKit). We could not identify subtypes of ICC, as IC-SMP or IC-MP in the appendix. The IC-LM were reduced compared to the colon. The IC-CM were numerously and regularly distributed. There were no differences in the reduced incidence of ICC between normal vermiform appendix, acute inflamed and chronic inflamed appendicitis.In conclusion and conformance with other observations the appendix has a physiological motility disorder and koprosthasis. Only if some influences of presumably additional cofactors (e.g. inflamation, lymphoid hyperplasia, obstruction), the koprosthasis is intensified, the mucosa is irritated and the appendicitis is developed.

Magister Scientiae (Physiotherapy) - MSc(Physio) / Millions of patients with burns require medical attention each year. Impairments, disabilities and handicap due to burn injuries among children are increasing. One possible reason could be that burn injury prevention were not given as much attention as infectious diseases such as leprosy, and tuberculosis (TB). The purpose of the study was to compile a profile of burn injuries among children aged 0-12 years, who were treated at the Black Lion Hospital (BLH) between 1996 and 2001 in Ethiopia. A retrospective, quantitative study design was chosen. Data was collected from the hospital records of 250 children seen with burn injuries. Clinical data, such as the cause and severity of the burn, and socio-demographic data such as the age of the child and his or her caregivers, their socio-economic status and educational levels, were captured. Descriptive and inferential statistical analyses of the data were carried out between socio-demographic variables and the burn injuries. The Chi-squared statistical test was used to identify associations and differences between selected variables. The major causes of thermal burns were hot liquids (63.4%) and flames (36.6%). The highest prevalence of burn injuries occurred in those children in the care of illiterate caregivers (p<0.01). The highest risk environment for burn accidents was identified as the kitchen (p<0.05). Most of the burns (64%) occurred in the children below the age of five years old. This finding was not statistically significant but it is of great clinical importance. Health and safety promotion programmes aimed at carers to minimize the risk of childhood disabilities due to burn injuries are recommended. Caregivers and school children have to be taught to use simple fire prevention procedures to avoid thermal burn injuries. Although the results of this study cannot be generalized, it provides a glimpse of the burn status and causes of thermal burn at BLH. However, in order to get more comprehensive information it is important to obtain information from more hospitals in the country through prospective studies.