Ausgehend von einer unspezifischen bakteriellen Infektion kann es während der Schwangerschaft zu einer Infektion der Fruchthöhle kommen. Das volle Bild dieser Art von Infektionen wird Amnioninfektionssyndrom genannt. Die Infektion der Fruchthöhle bedroht Mutter und Kind und die sofortige Entbindung würde ein rasches Abklingen der Infektion des Uterus herbeiführen. Auf der anderen Seite würde häufig eine Entbindung zu einem Zeitpunkt induziert, da das Kind zusätzlich zur Infektion durch die Unreife bedroht ist. Aus der Diagnostik heraus wird die Entscheidung über konservatives oder progressives Vorgehen getroffen. Es stellen sich folgende Fragen: 1. Sind die präpartal erhobenen klinischen Zeichen eines Amnioninfektionssyndromes relevant in der Diagnostik einer konnatal erworbenen neonatalen Infektion? 2. Sind die immunkompetenten Zellen des Neugeborenen in der Lage, inflammatorische Zytokine zu produzieren? 3. Gibt es lösliche Faktoren im Nabelschnurblut, die die Diagnostik einer Infektion des Neugeborenen entscheidend verbessern und die einen Zusammenhang mit einer Infektion der Plazenta aufweisen? 4. Besteht ein Zusammenhang zwischen der präpartalen klinischen Symptomatik eines Amnioninfektionssyndromes und den infektionsabhängigen löslichen Parametern im Nabelblut? Es wurden zwei prospektive Studien zur Beantwortung der Fragestellung durchgeführt. Im Rahmen der ersten Studie wurden 511 Fälle analysiert. Es fand eine Evaluierung der präpartalen klinischen Parameter bezogen auf das Ereignis neonatale Infektion und histologisch gesicherte Infektion der Plazenta statt. Die Konzentrationen der Zytokine Interleukin-6, Interleukin-8, Tumornekrosefaktor-a, G-CSF und der laborchemischen Parameter C-reaktives Protein und Procalcitonin wurde im Nabelschnurblut direkt nach der Geburt bestimmt. Diese Konzentrationen wurden in Bezug gesetzt zu klinischen Anzeichen einer Infektion des Neugeborenen und histologischen Zeichen einer Infektion der Plazenta. Außerdem wurden sie in Bezug gesetzt zu den präpartalen Symptomen eines Amnioninfektionssyndromes. In einer zweiten Studie wurden 42 Fälle analysiert. Mittels Durchflußzytometrie wurden Zellen aus Vollblut isoliert. Isoliert wurde die T-Zellpopulation CD 4 und CD 8 der Lymphozyten untersucht Eine intrazytoplasmatische Zytokinbestimmung nach Stimulation mit Ionomycin und Phorbol-12,13-Dibutyrat unter Verwendung von Monensin wurde durchgeführt. Bestimmt wurde die intrazytoplasmatische Zytokinfreisetzung der Zytokine Interleukin-6 und Interleukin-8. Die präpartalen Symptome mütterliche Temperaturerhöhung, mütterliche CRP-Erhöhung und fetale Tachykardie haben nur eine begrenzte Aussagekraft im Hinblick auf das Ereignis Neonatale Infektion. Während für die präpartal festgestellte fetale Tachykardie und die mütterliche Temperaturerhöhung eine Sensitivität für die "Neonatale Infektion" von 28,6 % bestimmt wurde, liegt dieser Wert für die präpartale mütterliche CRP-Erhöhung bei 45,5% deutlich höher. Die aus dem Nabelblut isolierten Lymphozyten sind in der Lage, auf eine unspezifische Stimulation hin, Interleukin-8 und Interleukin-6 zu produzieren. Signifikant höher liegt die Sekretion an Interleukin-6 dann, wenn die Kinder mit dem Verdacht auf eine peripartale Infektion geboren wurden oder wenn infektionsrelevante Ereignisse vor der Geburt aufgetreten waren. Von den im Nabelschnurblut untersuchten löslichen Parametern fällt auf, daß Procalcitonin mit einer Sensitivität von 93,3% und einer Spezifität von 73,1% ein sehr zuverlässiger Parameter zur Diagnostik einer neonatalen Infektion darstellt. Mit einer Sensitivität von 58,3% und einer Spezifität von 90,4% hebt sich auch der hochsensitive Nachweis des CRP im Nabelblut noch deutlich von den herkömmlich verwendeten Parametern ab. Nur eingeschränkte Aussagekraft auf das Ereignis "Neonatale Infektion" hat die Bestimmung des Interleukin-6. Die kombinierte Betrachtung der präpartal erhobenen klinischen Parameter fetale Tachykardie, mütterliche Temperaturerhöhung und mütterliche CRP-Erhöhung verbessert die vorgeburtliche Diagnostik einer intrauterin bestehenden Infektion deutlich. Der Nachweis der intrazellulären Interleukin-6- und Interleukin-8-Produktion durch neonatale Lymphozyten zeigt die Fähigkeit der zellvermittelten Immunität des Neugeborenen schon vor der Geburt auf bakterielle Infektionen reagieren zu können. Die differenzierte Reaktionsfähigkeit zeigt sich in der gesteigerten Interleukin-6-Syntheseleistung in all den Fällen, die in die "Infektionsgruppe" eingeschlossen waren. Von den löslichen Infektparametern im Nabelblut sticht das Procalcitonin als sehr zuverlässiger Marker sowohl einer Infektion des Neugeborenen als auch der histologisch gesicherten Infektion der Plazenta hervor. Auch Interleukin-6 sollte bestimmt werden. Die nachgewiesene Möglichkeit des Neugeborenen, inflammatorische Zytokine in hohen Konzentrationen als Antwort auf eine bakterielle Invasion produzieren zu können, scheint auch die Gefahr in sich zu bergen, durch eben dieses Interleukin-6 eine cerebral schädigende Reaktion zu erfahren. Zur Abschätzung dieses Risikos ist eine Bestimmung des Interleukin-6 im Nabelschnurblut empfehlenswert. / Starting with a nonspecific bacterial infection, during the pregnancy an infection of the amnion can occur. The full expression of this kind of infections is called chorioamnionitis. The infection of the amnion endangers mother and child, and the immediate delivery would produce a quick subsidence of the uterine infection. On the other hand a delivery would frequently be induced at a time when in addition to the infection the child is endangered by prematurity. Out of the diagnostic investigation the decision on conservative or progressive procedure is made. Following questions arise: 1. Are the prepartally ascertained clinical signs of a chorioamnionitis relevant in the diagnosis of a connatally acquired neonatal infection? 2. Are the immunocompetent cells of the neonate able to produce inflammatory cytokines? 3. Are there soluble factors in the cord blood which decisively improve the diagnosis of an infection of the neonate and show a correlation with an infection of the placenta? 4. Is there a correlation between the prepartal clinical symptoms of an amniotic infection syndrome and the infection-dependent soluble parameters in cord blood? Two prospective studies were carried out in order to answer the question. Within the scope of the first study 511 cases were analyzed. An evaluation of the prepartal clinical parameters related to the occurence neonatal infection and histologically established infection of the placenta took place. The concentrations of the cytokines interleukin-6, interleukin-8, tumor necrosis factor-a, G-CSF and the lab-chemical parameters C-reactive protein and procalcitonin were measured in the cord blood directly after birth. These concentrations were related to clinical signs of an infection of the neonate and histological signs of an amniotic infection. In addition they were related to the prepartal symptoms of an amniotic infection syndrome. In a second study 42 cases were analyzed. Using flow cytometry cells were isolated from whole blood. The T cell population CD 4 and CD 8 of lymphocytes was isolatedly examined. An intracytoplasmic cytokine analysis after stimulation with Ionomycin and phorbol-12,13-dibutyrate using Monensin was performed. The intracytoplasmic cytokine release of interleukin-6 and interleukin-8 was determined. The prepartal symptoms maternal elevation of temperature, maternal CRP increase and fetal tachycardia are only poor prognostic predictors with regard to the occurence neonatal infection. While for the prepartally ascertained fetal tachycardia and the maternal rise of temperature a sensitivity for the "neonatal infection" of 28.6% was determined, for the prepartal maternal CRP increase this value is clearly higher with 45.5%. The lymphocytes isolated from cord blood are able to produce interleukin-8 and interleukin-6 on account of a nonspecific stimulation. The interleukin-6 secretion is significantly higher if the children were born with the suspicion of a peripartal infection or if infection-relevant occurences were arisen before birth. Regarding the soluble parameters examined from the cord blood, it is remarkable that with a sensitivity of 93.3% and a specificity of 73.1% procalcitonin shows to be a very reliable parameter for diagnosis of a neonatal infection. With a sensitivity of 58.3% and a specificity of 90.4% also the high sensitive detection of CRP in cord blood stands out clearly from the conventionally used parameters. The determination of interleukin-6 has only a limited meaningfulness with regard to the occurence "neonatal infection". The combined contemplation of the prepartally measured clinical parameters fetal tachycardia, maternal rise of temperature and maternal CRP elevation clearly improves the antenatal diagnosis of an intrauterine infection. The detection of intracellular interleukin-6 and interleukin-8 production through neonatal lymphocytes shows the capability of cell-mediated immunity of neonate to react to a bacterial infection before birth. The differentiated reactivity is shown in the increased interleukin-6 synthesis in all those cases which were included in the "infection group". Among the soluble infection parameters in cord blood the procalcitonin stands out as a very reliable marker of neonatal infection as well as the histologically established infection of the placenta. Interleukin-6 should also be determined. The proved possibility of the neonate to produce inflammatory cytokines in high concentrations as an answer to a bacterial invasion seems also to involve the risk to experience a cerebrally damaging reaction through exactly this interleukin-6. For estimation of this risk, an interleukin-6 analysis in cord blood is recommendable.

In dieser Arbeit werden die intratrachealen Doppler-Fluáparameter w?hrend der FAB bei 47 gesunden menschliche Feten im zweiten und dritten Trimenon analysiert. Die Dauer der Inspiration, die Dauer der Exspiration sowie die Atemfrequenz unterlagen zwischen den einzelnen Gruppen nur geringen Ver?nderungen. Wir konnten zwischen der 24. und der 35. SSW einen signifikanten Anstieg des medianen intratrachealen Fluávolumens w?hrend der regelm?áigen FAB mit zunehmendem Gestationsalter nachweisen. Das fetale Atemzugvolumen fiel dagegen nach der 36. SSW ab. Die Differenz zwischen dem inspiratorischen Fluávolumen und dem exspiratorischen zeigte einen interessanten Verlauf mit einer positiven Bilanz in den ersten vier Gruppen (20.-35. SSW) und eine negative Bilanz in der letzten Gruppe (36.-40. SSW). Dies k?nnte bedeuten, daá nach der 36. SSW w?hrend der ausgew?hlten Atemepisoden tendenziell mehr Fl?ssigkeit aus- als eingeatmet wurde. Unsere Untersuchungen zeigen, daá in den letzten Wochen vor der Geburt eine wichtige Umstellung der fetalen Ventilation stattfindet, die einen Abfall der Lungenfl?ssigkeit bewirkt. Ferner konnten wir zeigen, daá die Trachea beim Schafsfeten sonographisch darstellbar ist. Es konnte ferner gezeigt werden, daá die mittels hochaufl?sender Sonographie durchgef?hrten Trachealmessungen mit den pathologischen Messungen ?bereinstimmten. / Assessment of tracheal fluid flow was obtained in 47 healthy human fetuses (GA 20-40 weeks) in which FBM were seen by B-Mode scan. Color Doppler was applied to visualise the tracheal fluid flow, followed by spectral Doppler to record the velocity waveforms. The breathing rate, the inspiration and expiration time and the volume obtained by integration of the tracheal fluid flow displaced during fetal breathing were calculated. The fetal breathing rate was not different between the groups. Both the time of inspiration and expiration showed a significant increase at 24 weeks followed by a constant course until Term. The volume of tracheal fluid flow moved during inspiration (Vi) and expiration (Ve) increased until 35 weeks followed by a flattening until term suggesting either a reduction of lung liquid production or a diminished lung liquid volume. The median difference between Vi and Ve was positive in the first four age groups and negative in the last one, suggesting that mature fetuses have the tendency to expire more than to inspire. We furthermore showed that in the ovine fetus at mid-gestation shows that optimal views of the fetal trachea allowing accurate measurements can be obtained in almost all the cases.

Die dreidimensionale Sonographie ermöglicht die Beobachtung der menschlichen Morphogenese in utero. Ziel der vorliegenden Untersuchung war die Evaluierung der Darstellung der embryonalen und frühen fetalen Oberflächenmorphogenese mittels transvaginaler 3D-Sonographie unter Anwendung eines neuen Verfahrens (3D-Cut) zur Sichtoptimierung. Fünf Schwangere mit datierten Embryonen wurden longitudinal zwischen der 4. und 12. Woche p.m. transvaginal sonographiert. Die Untersuchungen wurden mit einem 3D-Ultraschallgerät der Firma Kretztechnik (VoluSonâ 530D MT) unter Verwendung einer 3D-Transvaginalsonde (5-8 MHz) durchgeführt. Die 3D-Daten wurden unter Einsatz des 3D-Cut-Verfahrens zu dreidimensionalen Oberflächenmodellen der Embryonen und Feten verarbeitet und mit embryologischen Präparaten gleichen Gestationsalters sowie den Ergebnissen bisheriger 3D-sonoembryologischer Studien verglichen. Die Darstellung der embryonalen und fetalen Oberflächenmorphologie gelang kontinuierlich ab der 6. Woche p.m.. Im chronologischen Verlauf zeigten die beobachteten Embryonen und Feten einen umfangreichen Gestaltwandel von einer C-förmigen Struktur ohne sonographisch fassbare Oberflächendetails hin zu einem Individuum von menschlicher Gestalt. Unter Berücksichtigung der sonographischen Auflösungsgrenzen war eine hohe Übereinstimmung zwischen den sonographischen Oberflächenmodellen und den korrespondierenden embryologischen Präparaten zu verzeichnen. Mit den Ergebnissen 3D-sonoembryologischer Voruntersuchungen ergab sich ebenfalls eine gute Korrelation. Die angewandte sonographische Methode ermöglicht auf nichtinvasive Weise eine detaillierte, systematische dreidimensionale Darstellung von Embryonen und frühen Feten in utero und vermittelt so wertvolle Informationen, die der embryologischen Forschung in dieser Weise bisher nicht zugänglich waren. / Three-dimensional sonography allows the observation of the human morphogenesis in utero. The objective of the presented study was the evaluation of the demonstration of embryonic and early fetal surface morphogenesis by means of transvaginal 3D-sonography using a new procedure (3D-Cut) for the optimization of image quality. Five pregnant women with dated embryos were examined longitudinally by transvaginal 3D-sonography between 3 and 11 completed weeks p.m.. The examinations were performed with a 3D-Ultrasoundmachine (VoluSonâ 530D MT) developed by Kretztechnik (Zipf/Austria) using a transvaginal 5-8 MHz-3D-transducer. The 3D-data were processed to three-dimensional surface models of the embryos and fetuses using the 3D-Cut-procedure and compared with embryologic specimens of corresponding gestational age as well as with the results of prior 3D-sonoembryological studies. Embryonic and early fetal surface morphology could be demonstrated continuously starting from 5 completed weeks p.m.. The observed embryos and fetuses showed an extensive morphological change from a C-shaped structure without sonographically detectable surface details to an individual of human shape. With consideration of the limited sonographic resolution a high agreement between sonographic surface models and the corresponding embryologic specimens was registered. A good correlation was also found with the results of prior 3D-sonoembryological studies. The applied sonographic method allows in a noninvasive way a detailed systematic three-dimensional demonstration of embryos and early fetuses in utero and provides thus valuable information, which was not accessible to embryological research in this way so far.

Typescript (photocopy). / Digitized by Kansas Correctional Industries

Previous epidemiological evidence from a number of studies supports the hypothesis that the risk of essential hypertension, coronary heart disease and non-insulin dependent diabetes is, in part, programmed by intrauterine nutritional status. An increasing number of human studies indicate that the developing kidney is particularly vulnerable to the adverse effects of fetal growth retarding influences. In animals growth retarding diets or other insults, which have an impact on the development of cardiovascular functions, also appear to impact upon nephron number. In this study, the feeding of a 9% casein diet to pregnant rats, a mild protein restriction, reduced nephron number in the offspring, which progressively declined with age compared to those exposed to an 1 8% control diet. At weaning low-protein exposed offspring had hypertension and evedence of renal insufficiency. On natural death, the kidneys from aged male rats exposed to both low-protein and control maternal diets had a higher incidence glornerulosclerosis and renal disruption than females. Supplementing the maternal 9% casein diet with 3% glycine, 1.5% urea and 3% alanine in the rat normalised nephron number in the offspring. Only the addition of glycinc in the maternal low- protein diet prevented the appearance of high blood pressure in the offspring. In this study it has been demonstrated that in humans, those of a low birth weight or ponderal index, a marker of fetal undernutrition, had evidence of increased glomerular permeability, but not elevated blood pressure at age 10. This association was not evident at age 12 or in a separate cohort of young adults. It is possible that hypertension and a reduced nephron reserve are not causally associated. The evidence from this thesis suggest that prenatal undernutrition may programme renal structure in later life, but that renal programming is not one of the primary mechanisms leading to hypertension

Motor vehicle accidents are statistically the major cause of accidental severe injuries for pregnant women and fetuses fatality. Volunteers, post mortem human surrogates, anthropomorphic crash test devices and computational occupant models are used to improve human safety in motor vehicle accidents. However, due to the ethical issues, pregnant women and their fetuses cannot be used as volunteers or post mortem human surrogates to investigate the effects of crashes on them. The only anthropomorphic test device representing pregnant women is very limited in design and lacks a fetus. There is no computational pregnant occupant model with a fetus other than 'Expecting'. This thesis focuses on understanding the risk of placental abruption for pregnant drivers involved in road accidents, hence assessing the risk to fetus fatality. An extensive review of existing models in general and pregnant women models in particular is reported. The time line of successive development of crash test dummies and their positive effect on automotive passive safety design are examined. 'Expecting', the computational pregnant occupant model with a finite element uterus and a multibody fetus, is used in this research to determine the strain levels in the uteroplacental interface. External factors, such as the effect of restraint systems and crash speeds are considered. Internal factors, such as the effect of placental location in the uterus, and the inclusion and exclusion of a fetus are investigated. The head of the multibody fetus is replaced with a deformable head model to investigate the effects of a deformable fetus head on strain levels. The computational pregnant driver model with a fetus offers a more realistic representation of the response to crash impact hence provides a useful tool to investigate fetus safety in motor vehicle accidents. Seat belt, airbag and steering wheel interact directly with the pregnant abdomen and play an important role on fetus safety in motor vehicle accidents. The results prove that the use of a three-point seat belt with the airbag offer the greatest protection to the fetus for frontal crash impacts. The model without a fetus underestimates the strain levels. The outcome of this research should assist automobile manufacturers to address the potential safety issues at the design level.

Dissertation (PhD)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: Introduction Despite advances in insulin therapy, the side effects associated with diabetes mellitus still remain. Pancreas transplantation has benefited diabetics with end-stage renal failure by reversing the diabetic state and preventing or reversing the progression of diabetes associated diseases. Currently the side effects associated with lifelong immunosuppression preclude pancreas transplantation as a viable treatment option for both type I and II diabetics. In the laboratory, transplanted rat foetal pancreata have been shown to be able to reverse the clinical signs of streptozotocin-induced diabetes in an isogeneic model. Reversal of diabetes by allogeneic foetal rat pancreas transplantation, although possible has proved to be more difficult due to fierce rejection of the grafts and the diabetogenic effects of conventional immunosuppressants. Aims One of the goals, focus and intentions of this laboratory study in rodents, is to contribute new information to the scientific literature. The potential to “reverse” the diabetic state by allogeneic foetal pancreatic transplantation, was the main stimulus for this study. Methods Foetal pancreata of 16-18 days gestation were transplanted into a surgically prepared renal subcapsular space. Immunosuppressive protocols used to prevent rejection of the allogeneic foetal rat pancreata included donor specific transfusion (DST), cyclosporine [a calcineurin inhibitor (CsA)], mycophenolate mofetil [a purine syntase inhibitor (MMF)], and a mouse anti-rat CD4 monoclonal antibody (W3/25). Immunosuppressants were used as monotherapies and in combination. Results Isogeneic foetal rat pancreas transplantation resulted in the growth and development of mature insulin producing islets of Langerhans at the site of engraftment. Allogeneic foetal pancreatic transplantation without immunosuppression resulted in complete rejection of the grafts at 14 days post-transplantation. Histological assessment of allografts at 14 and 30 days post-transplantation showed that CsA was able to prevent acute rejection in our rat models although graft scores and survival were improved if CsA was combined with MMF. Intraperitoneal anti-CD4 monoclonal injections were well tolerated, and if given daily effectively prolonged graft survival up to 30 days. Combining DST with anti-CD4 and CsA induction therapy provided long-term graft survival without daily immunosuppression. This combination, together with allogeneic foetal rat pancreas transplantation, was effective in reversing the clinical signs of experimentally induced diabetes. To my knowledge these are the first published results in which reversal of streptozotocin induced diabetes was achieved by fully MHC mismatched foetal rat pancreatic transplantation. Conclusion Foetal rat pancreatic transplantation is a potential source of endocrine replacement, which, with effective immunosuppression allows for the development of functional islets able to reverse the clinical signs of experimentally induced diabetes in an allogeneic rat model. An unique immunosuppressive protocol, with potential clinical relevance in the human, combines anti-CD4 mAb, CsA and DST induction therapy, which alleviates the burden of daily immunosuppression and associated side effects. / AFRIKAANSE OPSOMMING: Inleiding Ten spyte van die vordering met modeme insulienterapie bly die newe-effekte, waarmee diabetes mellitus geassosieer is, steeds ‘n probleem vir diabete. Diabetiese pasiente met eindstadium nierversaking trek geweldig voordeel uit nier-pankreasoorplantings wat die diabetes omkeer en die progressie van diabetesverwantesiektes voorkom of selfs omkeer. Die newe-effekte van lewenslange immuunonderdrukking skakel pankreasoorplanting uit as ‘n lewensvatbare behandelingsopsie vir tipe I of II diabete. In ‘n streptozotosien-gei'nduseerde diabetiese rotmodel kan isogenei'ese fetale pankreasoorplanting die kliniese tekens van diabetes omkeer. Die omkering van streptozotosien-gei'nduseerde diabetes deur allogeneiese fetale pankreasoorplanting behoort moontlik te wees indien verwerping en die diabetogeniese newe-effekte van konvensionele immuunonderdrukkers oorkom word. Doelstellings Een van die mikpunte, fokusse en oogmerke van hierdie laboratorium studie in knaagdiere, is om ‘n betekenisvolle bydrae tot nuwe kennis in die wetenskaplike literatuur, te maak. Die potensiaal om die diabetiese toestand deur allogeneiese fetale pankeasoorplanting om te keer, was die hoof stimulus vir die studie. Metodes Fetale rotpankreata van 16-18 dae gestasie was in ‘n chirurgies voorbereide spasie onder die nierkapsel oorgeplant. Immuunonderdrukkende protokolle, vir die voorkomming van verwerping van die allogeneiese fetale pankreasoorplantings, het donorspesifiekeoortappings (DST), siklosporien [‘n kalsineurien inhibitor (CsA)], mikofenolaat mofetiel [‘n purien sintase inhibitor (MMF)] en ‘n anti-rot CD4 monoklonale antiliggaam (W3/25) ingesluit. Die immuunonderdrukkers is as mono- of as kombinasieterapie gebruik. Resultate IsogeneTese fetale rotpankreasoorplanting het tot die ontwikkeling van volwasse insulienproduseerende eilande van Langerhans gelei, wat die kliniese tekens van streptozotosien-gei'nduseerde diabetes kon omkeer. Allogenei'ese fetale rotpankreasoorplanting sonder immuunonderdrukking het tot algehele verwerping van die oorplanting binnel4 dae na oorplanting gelei. Histologiese beoordeling van die oorplantings 14 en 30 dae na oorplanting het getoon dat CsA akute verwerping van fetale pankreasoorplantings in die rotmodelle voorkom. Indien CsA met MMF gekombineer word, word die oorplantings-telling en oorlewing verbeter. Intraperitoneale anti-CD4 monoklonale inspuitings was goed verdra, en indien daagliks toegedien, het dit die oorlewing van die pankreasoorplantings effektief tot 30 dae verleng. Die kombinasie van DST, anti-CD4 en CsA induksieterapie het tot langtermyn oorlewing van die pankreasoorplantings gelei sonder verdere daaglikse immuunonderdrukking. Die induksieterapie in kombinasie met allogenei'ese fetale pankreasoorplanting was effektief in die omkering van die kliniese tekens van streptozotosien-gei'nduseerde diabetes in die rot. Hierdie is, sover ek weet, die eerste keer dat omkering van streptozotosien-gei'nduseerde diabetes suksesvol met ‘n volledige MHC onverenigbare allogenei'ese fetale pankreasoorplanting behaal is. Gevolgtrekkings Fetale rotpankreasoorplanting is ‘n potensiele bron vir endokrien vervangingsterapie, wat met effektiewe immuunonderdrukking tot die ontwikkeling van funksionele eilande van Langerhans lei, wat die vermoe het om die kliniese tekens van experimenteel-ge'induseerde diabetes in ‘n allogeneiese rotmodel om te keer. ‘n Unieke immuunonderdrukkingsprotokol, met kliniese relevansie, kombineer DST met anti-CD4 mAb en CsA induksieterapie wat die las van daaglikse immuunonderdrukking en die geassosieerde newe-effekte van konvensionele immuunonderdrukking verlig.

published_or_final_version / Paediatrics / Doctoral / Doctor of Philosophy

<p>The aim with this thesis was to assess the impact of prenatal ultrasound exposure on psychotic illness, childhood brain tumors (CBT) and school achievement, and to evaluate prenatal X-ray exposure and the risk of CBT.</p><p>In a cohort study, children born in Malmö 1973-1978, where prenatal ultrasound was used routinely, were considered exposed (n=13, 212) and children born at hospitals with no use of ultrasound, were considered unexposed (n=357,733). Exposed men had a tendency toward a higher risk of schizophrenia. For other psychoses there were no differences between groups. Other factors related to place of birth might have influenced the results. </p><p>In a case control study, children born 1975-1984 with a diagnosis of CBT (n=512), and randomly selected control children (n=524) were included. Exposure data on X-ray and ultrasound from antenatal records was completed with information from the Medical Birth Register. We found no overall increased risk for CBT after prenatal X-ray exposure. When stratifying by histological subgroups, primitive neuroectodermal tumors had the highest risk estimates. For ultrasound exposure, no increased risk for CBT was seen and numbers of examinations or gestational age at exposure had no substantial impact on the results. </p><p>In a follow-up of a randomized trial on prenatal ultrasound scanning 1985-87, we assessed the children’s school grades when graduating from primary school (15-16 years of age). We performed analyses according to randomization, ultrasound exposure in the second trimester and exposure at any time during pregnancy. There were no differences in school performance for boys or girls according to randomization or exposure in the second trimester. Boys exposed to ultrasound any time during fetal life had a reduced mean score in physical education and small, non-significant increased risk of poor school performance in general.</p>

Increased environmental heat causes early embryonic death before implantation. This study was designed to examine tissues of dams exposed to environmental temperatures of 36°C and to examine 72 hour old embryos from these dams. Results showed adult mice exposed to heat stress had significant changes in liver morphology with hepatocyte swelling and vacuolization of the cytoplasm, organelles in the hepatocytes were displaced next to the cell membrane. After 48 hours of recovery from heat stress, liver morphology appeared normal. Embryos from heat stressed dams had delayed development indicated by increased 2alpha helical cellular inclusions. Embryos responded differently to different fixation techniques indicated permeability changes in either the zona pellucida or cellular membranes. Litter size or pup survivability from heat stressed dams allowed to recover indicated changes seen at this point were reversible