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Diss. (sammanfattning) Linköping : Univ., 2001. / Härtill 6 uppsatser.

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

Unauthorized reproduction of this article is prohibited. Background:Mental health conditions are common among persons with HIV (PWH). An understanding of factors associated with prescription medication use for these conditions and clinical impact of the prescription medications may improve care of mental health disorders in PWH.Methods:Psychotropic medication use was examined among PWH within the AIDS Clinical Trials Group A5322 (HAILO) study. Multivariable logistic models and Cox regression models estimated the association between psychotropic medications (any/none) with baseline and incident slow gait (>1 s/m) and neurocognitive impairment (NCI) for more than 4 years.Results:Of 1035 participants, the median age was 51 years.81% were men, 30% black, non-Hispanic, and 20% Hispanic. Psychotropic medication use was similar between men (34%) and women (38%; P = 0.19). PWH using psychotropic medications had greater odds of baseline slow gait {odds ratio 1.61, [95% confidence interval (CI): 1.23 to 2.10]; P < 0.001}. Men but not women using psychotropic medications had an increased risk of developing slow gait [hazard ratio 1.85; (1.29 to 2.65) vs 0.77; (CI: 0.35 to 1.68), P interaction = 0.045]. The sex-specific odds ratios for medication use and NCI were qualitatively but not statistically different [men: 1.79; (1.14-2.80); women: 1.27; (0.56-2.90); P interaction = 0.47]. Psychotropic medication use was associated with an increased risk of incident NCI [hazard ratio 2.18; (95% CI: 1.23 to 3.84), P = 0.007] in both men and women.Conclusions:Psychotropic medications are associated with impairment in functional outcomes of aging, with a greater risk of baseline NCI and incident slow gait among men. Further investigation is needed to optimize outcomes in PWH and prescription of psychotropic medications among both men and women.

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Recent technological innovations and the need for increased safety on the world's roads have led to the introduction of In- Vehicle Information Systems (IVIS). These systems will provide navigation and advisory information to drivers while they are driving. One aspect of these systems, In-vehicle Signing Information Systems (ISIS), would provide the warning, regulatory, and advisory information that is currently found on road signs. These systems may be of particular benefit when external elements such as rain, snow, or night driving reduce or eliminate the opportunity for drivers to detect road signs. This study attempts to determine what benefits, if any, are realized by drivers using this system. Fifty-eight drivers operated an instrumented Oldsmobile Aurora under eight conditions. The eight conditions consisted of a daylight-clear weather-ISIS condition, a daylight-clear weather-No ISIS condition, a daylight-rain-ISIS condition, a daylight-rain-No ISIS condition, a night-clear weather-ISIS condition, a night-clear weather-No ISIS condition, a night-rain-ISIS condition, and a night-rain-No ISIS condition. Younger drivers (18-30 years old) and older drivers (65 years or older) took part in this study. Three measures of driver performance were collected along with subjective preference data. Each measure was evaluated in order to determine what impact, if any, weather, time of day, age, and ISIS use had on performance. Subjective data was evaluated to determine driver preference and acceptance of the ISIS display. The results indicated that use of the ISIS display led to reduced speeds and greater reaction distances for all drivers. Evidence was found that seems to indicate that older drivers may receive a greater benefit in complex, unfamiliar, or low visibility situations. Evidence was also found that indicates that all drivers may receive a greater benefit at night for the complex or unfamiliar situations. Subjectively, the majority of the drivers indicated that the ISIS display made them more aware of road sign information. / Master of Science

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.