Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 1999. / Härtill 7 uppsatser.

The suspected teratogenicity of Diphenylhydantoin (DPH) in man is important, especially to the 0.3 to 0.5% of pregnant women who are epileptic and, therefore, candidates for anticonvulsant drug therapy. To separate the teratogenic effect of epilepsy from DPH treatment, an animal model closely approximating the human condition was developed to meet the following criteria: (i) the test animal must have spontaneous seizures (ii) the seizures must be controlled or eliminated by DPH treatment (iii) the drug must be administered orally (iv) serum DPH levels must fall within the optimal human therapeutic range between 5 and 20 micrograms per ml serum (v) treatment must begin prior to mating and continue throughout gestation (vi) the offspring of treated animals must exhibit the spectrum of malformations observed in the offspring of epileptic women The first criterion was met by mutant quaking (qk) mice. The seizure activity of these animals was reduced (from 2.1 to .34 seizures per mouse day) by DPH treatment. To separate the effect of this gene from that of the DPH in the etiology of the malformations, heterozygous (+/qk) and homozygous non- quaking (+/+) mice were also studied. Monitoring of DPH levels with the SYVA Emit spectrophotometry assay technique indicated serum concentrations within the human therapeutic range at 40 and 60 mg/kg body weight dosages. The incidence of fetuses born with skeletal or soft-tissue abnormalities increased with increasing DPH dosages. This was observed in all three genotypes. The ability of the untreated quaking (qk/qk) dams to -produce normal offspring implicates the drug rather than the mutant gene as the cause of malformations. A preliminary application of this animal model produced what can be considered the mouse equivalent of the fetal hydantion syndrome. The similarities between the human and mouse syndromes include prenatal growth deficiency, neural, cardiac, orofacial, ocular and genitourinary anomalies. Further large-scale application of the model should provide insight into the role of DPH in the etiology of the malformations observed amongst the offspring of epileptic women on hydantoin anticonvulsant drug therapy. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Objective. Most biomarker studies of maternal smoking have been based on a single blood or urinary cotinine value, which is inadequate in capturing maternal tobacco exposure over the entire pregnancy. This thesis used maternal hair biomarkers to investigate the association between maternal active and passive smoking, and birthweight for gestational age (BW for GA). / Methods. Subjects were 444 term controls drawn from 5,337 participants of a multi-centre nested case-control study of preterm birth in Montreal. Maternal hair, collected after delivery, was measured for average nicotine and cotinine concentration across the pregnancy, assuming hair growth of 1 cm/month. The BW for GA z-score used Canadian population-based standards. Multiple linear regression was used to assess effects on the z-score, after controlling for potential confounders. / Results. In regression models for maternal active smoking analysis, the addition of hair nicotine to models containing either self-report or hair cotinine or both self-report and cotinine explained significantly more variance in the BW for GA z-score (p=0.009, p=0.017, and p=0.033, respectively). In maternal passive smoking analysis, no significant effect of ETS on BW for GA was found using hair biomarkers. / Conclusion. These results indicate that hair biomarkers are sensitive tools capable of predicting reductions in birthweight for maternal active smoking. The stronger results obtained for nicotine are reflective of the fact that hair nicotine is a better measure of maternal smoking, but it could also suggest that nicotine plays an aetiologic role in affecting foetal growth.

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BACKGROUND:A inverse correlation has been found between changes in ionized calcium concentrations and the addition of albumin in vitro, which may explain adverse cardiovascular effects attributed to exogenous albumin in vivo. The purpose of this investigation was to determine the interaction (if any) between exogenous 25% albumin administration (100 ml given over < 30 min) and calcium concentrations in patients, all but one of whom were in an intensive care unit.RESULTS:There were no significant differences in the ionized calcium concentrations obtained before, at the end and 6 h after the administration of albumin (1.09 +/- 0.23, 1.06 +/- 0.22, 1.06 +/- 0.21 mmol/l, respectively). Similarly, there were no significant differences in the total calcium concentrations between these same time periods (2.03 +/- 0.18, 2.05 +/- 0.20, 2.08 +/- 0.23 mmol/l, respectively).CONCLUSIONS:In patients receiving infusions of 25% albumin, it appears that circulating calcium concentrations are well regulated by homeostatic mechanisms. Albumin infusions had no effect on calcium concentrations, although it is possible that temporary changes of questionable clinical importance may have occurred between measurement periods.

The teratogenic effects of prenatal alcohol exposure can significantly influence the development of a child, which may result in a range of structural, cognitive and behavioural abnormalities. The severity of these effects can vary and fall under the fetal alcohol spectrum disorder (FASD). South Africa hosts the highest prevalence rate (12%) of this disorder in the world. All conditions included in the FASD spectrum are completely preventable through maternal abstinence of alcohol during pregnancy. At present, very limited information is available regarding how much pregnant women in South Africa know about adverse effects caused by prenatal alcohol exposure. This study aimed to determine pregnant women’s awareness of alcohol’s potential teratogenic effects on pregnancy and their knowledge of the features and characteristics associated with fetal alcohol syndrome (FAS), the most severe of the FASD conditions. Additionally, the study compared the awareness and knowledge of pregnant women attending private antenatal centres, to those attending an antenatal clinic at Charlotte Maxeke Johannesburg Academic Hospital, a state hospital in the Johannesburg area. Participants (n=211) completed a self-administered questionnaire at their private antenatal class or state clinic. A total of 211 questionnaires were analysed; 107 questionnaires from the state antenatal clinic and 104 from the private antenatal centres. The awareness levels regarding alcohol use in pregnancy were found to be very similar amongst the private (52%) and state (55%) participants. However, results indicated that significantly more private participants (19%), compared to state participants (3%) could be classified as having knowledge of the condition FAS. Overall, this study found that pregnant women from various backgrounds have limited knowledge of the harms caused by alcohol use during pregnancy. Misconceptions about the acceptable levels of maternal alcohol consumption and the effects thereof were also evident. The results of this research highlights that prevention strategies and awareness campaigns regarding alcohol use during pregnancy should incorporate information on the severity and permanent nature of FAS, as well as highlighting the fact that all types of alcoholic beverages can result in this condition. Also, these campaigns should focus on informing women that no level of alcohol is acceptable during pregnancy, as any amount may have potentially teratogenic effects on the developing fetus.

Introduction: Poultry workers have an increased risk of respiratory symptoms associated with various irritant and allergenic exposures causing airway inflammation. This study investigated the levels of (1-3)-β-D glucan exposure in several poultry farming processes. The objectives involved categorising the different tasks undertaken in the poultry industry. After which a method was established and validated to detect and quantify the levels of (1-3)-β-D glucan using the Glucatell assay. This assay was used to measure the amount of (1-3)-β-D glucan poultry farm workers were exposed to using personal sampling. Thereafter, general respiratory symptoms were described briefly via the administration of a respiratory questionnaire. Method: A total of 308 personal air samples were collected from several poultry farming processes (rearing, laying, hatchery, broilers, catching) of a large poultry farm in the North West Province. A walkthrough checklist was used to obtain information on various exposure determinants such as farm size, number of chickens, ventilation system, bedding material used and poultry feed used. The Glucatell assay (Associates of Cape Cod, East Falmouth, MA, USA) was used to quantify the concentration of (1-3)-β-D glucans in the air samples. Results: The geometric mean concentrations of (1-3)-β-D glucans ranged from 24.38 to 645.98 ng/m3 across the various poultry farming processes investigated. Workers in the broiler farms were exposed to two times higher levels of (1-3)-β-D glucans compared to those in the breeding farms. The sizes of the broiler farm houses as well as the age of the chickens were among the main determinants of exposure. The larger broiler farm houses (GM=5.2 ng/m3, GSD=3.74) had significantly (p<0.05) lower levels than the smaller broiler farm houses (GM=6.4 ng/m3, GSD=2.14) whilst houses with older chickens had higher (1-3)-β-D glucan levels (G=5.8 ng/m3,

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.