http://hdl.handle.net/1956/947 Search the Channel search http://bora.uib.no/simple-search http://hdl.handle.net/1956/2392 Title: Portal and umbilical venous distribution in the human fetus : a longitudinal ultrasound study <br/> <br/>Authors: Kessler, Jörg <br/> <br/>Abstract: Knowledge of the venous perfusion of the human fetal liver is fragmentary and mainly limited to the umbilical circulation. Current ultrasound technology makes it possible to study blood flow noninvasively and to give new insights into the developmental changes during gestation. AIMS: The general aim of the study was to map the hemodynamics of the venous supply to the fetal liver in humans. In detail: to establish longitudinal reference ranges for ductus venosus flow velocities and waveform indices (paper I), to establish a technique for direct flow measurement in the main portal stem and study its development during the second half of pregnancy (paper II), to assess the flow velocity pattern in the left portal vein (paper III), and to determine the distribution of venous blood supply within the liver and explore the impact of maternal and fetal factors (paper IV). MATERIAL AND METHODS: After informed written consent, 160 women with low-risk pregnancies were recruited to a longitudinal study according to a protocol approved by the Regional Committee for Research Ethics (REK-Vest 04/3837). 4-5 ultrasound examinations, each lasting 60 minutes, were done at four weeks intervals between 20 and 40 weeks of gestation. At each session the inner diameter was measured in: 1. the intraabdominal portion of the umbilical vein, 2. the ductus venosus, 3. the main portal stem, and 4. the left portal vein. In the same vessels, time-averaged maximum flow velocties were measured by Doppler ultrasound. Volume blood flow was calculated and normalised for fetal weight. Mean and percentile curves were constructed using regression analysis and multi-level modelling. The impact of maternal and fetal factors on liver blood flow was investigated by deviance statistics. RESULTS: The established longitudinal reference ranges for ductus venosus flow velocities and waveform indices allow the calculation of conditional percentiles, which are narrower and commonly shifted compared to those of the entire population (Paper I). Blood flow in the main portal stem was pulsatile in 99%. Both diameter and flow velocities doubled during the observation period. Correspondingly, blood flow increased throughout gestation, and so did flow, normalised for fetal weight (Paper II). Flow velocities in the left portal branch increased throughout gestation. We found pulsatile flow in 69%, usually directed towards the right lobe. However, intermittent flow reversal occurred during respiratory movements, and continuous reversal in 8% of the observations close to term (Paper III). Total venous liver flow increased throughout gestation, while normalised flow decreased. Lobe specific flow distribution was stable during gestation directing 60% of the total venous liver flow to the left and 40% to the right lobe. The umbilical vein was the dominating venous blood source, but the portal fraction grew during the last trimester. Venous liver flow and its components were related to birthweight, while lobe specific flow and fractional flow distribution to the lobes were related to pregnancy weight gain (Paper IV). CONCLUSION: We have established longitudinal reference ranges for all components of venous liver supply and the ductus venosus in the human fetus. The reference ranges for ductus venosus velocimetry are appropriate for serial measurements, especially when conditional terms are applied (Paper I). The present established technique of assessing flow in the main portal stem had a high success rate and could be used to show an increasing hemodynamic importance of the main portal stem towards term (Paper II). The umbilico-portal watershed is usually situated in the right liver lobe, but may shift towards the left portal vein even in circulatory uncompromised fetuses. The time-averaged maximum flow velocity is suggested for the evaluation of the umbilico-portal watershed (Paper III). The relationship between venous liver flow and birth weight may indicate a link between liver perfusion and fetal growth. The growing portal fraction of the total venous blood flow signifies the high circulatory priority given to the splanchnic circulation close to term. The relationship between low pregnancy weight gain and the distributional shift in favour of left liver lobe perfusion may be part of an adaptation to various intrauterine environments (Paper IV). Mon, 25 Jun 2007 22:58:59 GMT http://hdl.handle.net/1956/2371 Title: Hereditary Colorectal Cancer <br/> <br/>Authors: Stormorken, Astrid Tenden Thu, 12 Apr 2007 22:58:59 GMT http://hdl.handle.net/1956/2325 Title: Assessing medical students’ attitudes towards learning communication skills – which components of attitudes do we measure? <br/> <br/>Authors: Anvik, Tor; Gude, Tore; Grimstad, Hilde; Baerheim, Anders; Fasmer, Ole B.; Hjortdahl, Per; Holen, Are; Risberg, Terje; Vaglum, Per <br/> <br/>Abstract: Background. The Communication Skills Attitudes Scale (CSAS) created by Rees, Sheard and Davies and published in 2002 has been a widely used instrument for measuring medical students' attitudes towards learning communication skills. Earlier studies have shown that the CSAS mainly tests two dimensions of attitudes towards communication; positive attitudes (PAS) and negative attitudes (NAS). The objectives of our study are to explore the attitudes of Norwegian medical students towards learning communication skills, and to compare our findings with reports from other countries. Methods. The CSAS questionnaire was mailed simultaneously to all students (n = 3055) of the four medical schools in Norway in the spring of 2003. Response from 1833 students (60.0%) were analysed by use of SPSS ver.12. Results. A Principal component analysis yielded findings that differ in many respects from those of earlier papers. We found the CSAS to measure three factors. The first factor describes students' feelings about the way communication skills are taught, whereas the second factor describes more fundamental attitudes and values connected to the importance of having communication skills for doctors. The third factor explores whether students feel that good communication skills may help them respecting patients and colleagues. Conclusion. Our findings indicate that in this sample the CSAS measures broader aspects of attitudes towards learning communication skills than the formerly described two-factor model with PAS and NAS. This may turn out to be helpful for monitoring the effect of different teaching strategies on students' attitudes during medical school. Thu, 29 Mar 2007 22:58:59 GMT http://hdl.handle.net/1956/2299 Title: Lipogenic effects of antipsychotic drugs in cultured cells and in rat <br/> <br/>Authors: Fernø, Johan <br/> <br/>Abstract: The etiology of the serious psychiatric disorder schizophrenia is unknown. Epidemiological studies indicate a high heritability with a complex pattern of transmission. Moreover, structural and genetic findings indicate that both neuronal and glial function is affected, including oligodendrocyte and myelin abnormalities. Antipsychotic drugs are used to treat and ameliorate the symptoms of schizophrenia. Drug-mediated Dopamine D2-receptor blockage is probably necessary for reducing the positive symptoms (hallucinations, delusions) of schizophrenia, but the mechanism(s) involved in the improvement of other schizophrenic symptoms (negative and cognitive) are less well established. Unfortunately, there are several side effects associated with antipsychotic drug treatment, with increasing focus on weight gain and other metabolic adverse effects. To gain further insight into the mechanisms of antipsychotic drug action, we applied microarray technology and quantitative real-time PCR to investigate drug-induced changes in global gene expression in various cultured human cell lines, including glial-like cells, neuronlike cells and liver cells. We found that several typical and atypical antipsychotic drugs elevated the expression of genes involved in cellular lipid biosynthesis, including HMG-CoA reductase and fatty acid synthase that are essential enzymes in cholesterol- and fatty acid biosynthesis, respectively. These genes are controlled by the SREBP transcription factors, which we found activated by antipsychotic drugs on the protein level. The increase in gene expression had a functional outcome, as demonstrated by accumulation of intracellular cholesterol and triglycerides. Although with differences in efficacy, most of the tested antipsychotic drugs induced SREBP activation in cell culture. In our studies, the effect was more pronounced in glial cell lines than in neuronal-like cell lines. Antipsychotic-induced 10 SREBP activation was also seen in hepatocytes, indicating that clinically significant effects might occur in tissues other than the CNS. In a context of therapeutically relevant serum concentrations, clozapine and chlorpromazine appear as the most potent SREBP activators. Interestingly, clozapine has superior efficacy in otherwise treatment-resistent schizophrenia. Clozapine also has the highest liability to induce weight gain, and we further investigated the ability of clozapine to induce lipogenesis in vivo. Indeed, in rats exposed to a single intraperitoneal dose of clozapine we observed a marked increase in hepatic lipid levels and altered expression of several genes involved in the control of lipid homeostasis (e.g. SREBP, PPARα and LXRα). In summary, we have identified transcriptional activation of cellular lipogenesis as a new mechanism of action of antipsychotic drugs. Enhanced cholesterol synthesis in the CNS may have therapeutic implications (glia-produced cholesterol serves as a glial growth factor to promote synaptogenesis and myelination), whereas increased lipid production in the liver and adipose tissues may be linked to the well-known metabolic side effects of these drugs. We propose that our findings provide new insight into the molecular mechanisms of antipsychotic drugs and provide new candidate genes for disease susceptibility and drug response in schizophrenia. Wed, 09 May 2007 22:58:59 GMT http://hdl.handle.net/1956/2208 Title: Hyperoxia retards growth and induces apoptosis and loss of glands and blood vessels in DMBA-induced rat mammary tumors <br/> <br/>Authors: Raa, Anette; Stansberg, Christine; Steen, Vidar M.; Bjerkvig, Rolf; Reed, Rolf K.; Stuhr, Linda E. B. <br/> <br/>Abstract: Background: This study investigated the effects of hyperoxic treatment on growth, angiogenesis, apoptosis, general morphology and gene expression in DMBA-induced rat mammary tumors. Methods: One group of animals was exposed to normobaric hyperoxia (1 bar, pO2 = 1.0 bar) and another group was exposed to hyperbaric hyperoxia (1.5 bar, pO2 = 1.5 bar). A third group was treated with the commonly used chemotherapeutic drug 5- Fluorouracil (5-FU), whereas animals housed under normal atmosphere (1 bar, pO2 = 0.2 bar) served as controls. All treatments were performed on day 1, 4, 7 and 10 for 90 min. Tumor growth was calculated from caliper measurements. Biological effects of the treatment, was determined by assessment of vascular morphology (immunostaining for von Willebrandt factor) and apoptosis (TUNEL staining). Detailed gene expression profiles were obtained and verified by quantitative rtPCR. Results: Tumor growth was significantly reduced (~57–66 %) after hyperoxic treatment compared to control and even more than 5-FU (~36 %). Light microscopic observations of the tumor tissue showed large empty spaces within the tissue after hyperoxic treatment, probably due to loss of glands as indicated by a strong down-regulation of glandular secretory proteins. A significant reduction in mean vascular density (30–50%) was found after hyperoxic treatment. Furthermore, increased apoptosis (18–21%) was found after hyperoxic treatment. Conclusion: Thus, by increasing the pO2 in mammary tumor tissue using normobaric and moderate hyperbaric oxygen therapy, a significant retardation in tumor growth is achieved, by loss of glands, reduction in vascular density and enhanced cell death. Hyperbaric oxygen should therefore be further evaluated as a tumor treatment. Mon, 29 Jan 2007 22:58:59 GMT http://hdl.handle.net/1956/2134 Title: Genetics in Parkinson’s disease <br/> <br/>Authors: Kurz, Martin Thu, 14 Dec 2006 22:58:59 GMT http://hdl.handle.net/1956/2096 Title: Cognitive and psychosocial problems in children with epilepsy : a population-based approach <br/> <br/>Authors: Høie, Bjørg Thu, 11 Jan 2007 22:58:59 GMT http://hdl.handle.net/1956/2067 Title: A study of recurrent unipolar major depression and executive functions <br/> <br/>Authors: Stordal, Kirsten Irene <br/> <br/>Abstract: Background: Unipolar major depression is a prevalent disorder and is in the World Health Organisation’s (WHO) top five on their global burden of disease-list. For more than three decades, assessment of neurocognitive functioning in patients with mental disorders by use of neuropsychological tests has been performed for research purposes. Patients with schizophrenia have been extensively studied, but a substantial amount of research has also been performed on depressed patients. In patients with unipolar major depression, performance below that of healthy controls has been shown on tests measuring memory, attention, psychomotor speed and executive functions. Executive Functions (EF) are higher order neurocognitive functions that control and integrate other neurocognitive functions; dysfunctions have been associated with frontal lobe dysfunction. Still, there is a lack of studies investigating EF in the most prevalent form of unipolar major depression, patients with recurrent subtype. This thesis is based on four original research papers published in referee based international journals. In paper I, we question whether executive dysfunctions also are present in patients with recurrent unipolar major depression compared to healthy controls. The investigation includes pattern and severity of executive dysfunction. In paper II, we consider whether all patients with recurrent unipolar major depression have impairment of EF. Mental disorders can be regarded as both categorical and dimensional conditions: according to the continuum model unipolar major depression and schizophrenia can be viewed as different levels of general psychopathology (LGP). Paper III explores the continuum model of mental disorders. We investigate whether LGP explains more of the variance in EF than diagnosis (unipolar major depression versus schizophrenia). Elevated levels of the stress hormone cortisol are often found among depressed patients, and there is evidence that prolonged hypercortisolemia can be neurotoxic. Specifically, recurrent depression episodes may lead to progressive brain damage. It is uncertain if executive dysfunctions in recurrent unipolar major depression are associated with elevated cortisol levels. Therefore, the aim of paper IV was to explore whether level of saliva cortisol is correlated with level of executive dysfunctions in recurrent unipolar major depression. Method: Data were collected in the context of a Norwegian, cross-sectional, multi-centre study, the BOP, starting in 1998. In the BOP, patients with either a diagnosis of unipolar major depressive disorder (MDD), recurrent type (N=50) or schizophrenia (N=53) and healthy controls (N=50) were included. The patients were diagnosed by the Structured Clinical Interview for DSM-IV Axis I Disorders. Depressed patients scoring above 18 points on both the Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale were included. Other inclusion criteria were: age between 20 and 50, Norwegian language and normal vision and hearing. Patients were excluded if they had a history of head trauma, neurological disorder or developmental dysfunction, present alcohol or substance abuse, other medical conditions likely to affect neurocognitive functions or if they recently had received electro convulsive treatment. The clinical psychiatric evaluation was performed by five trained psychiatrists. In the BOP, a broad neuropsychological test battery was used to measure several domains of neurocognitive function. In this thesis, mainly tests assessing components of EF are used. The tests were administered by a licensed clinical neuropsychologists, a graduate psychology student or a medical doctor (Kirsten Irene Stordal) supervised by a neuropsychologists. Results: There was a tendency for patients with recurrent MDD to perform below healthy controls on all measures of EF (Paper I). A significant group difference was found for eight of ten measures. The executive dysfunctions were within -1.0 SD from the mean of the control group. While the components verbal fluency, inhibition, set-maintenance and working memory were affected in recurrent MDD, set-shifting and planning seemed to be spared. Whether this dysfunction could be found in all patients with recurrent episodes of depression, was uncertain. This was explored in the following paper, the result being that more than half of the patients with recurrent MDD had unimpaired EF when unimpairment was defined as performance above -1.0 SD of the sample mean of the control group on more than one component of EF (Paper II). The sub-group of patients without impairment of EF was characterised by higher intellectual abilities and fewer episodes of depression than the subgroup with EF impairment. In paper III we found EF impairment to be more strongly related to LGP than to diagnosis (MDD versus schizophrenia). In the last paper an inverse correlation between saliva cortisol and EF was found (Paper IV). Discussion: All the papers add to current knowledge in this field: The first paper in that patients with recurrent MDD have mild executive dysfunctions, and that seemingly all components of EF are affected. The second paper shows that more than half of patients with recurrent MDD have unimpaired EF when depressed, and that this subgroup has higher intellectual abilities and a history of fewer depression episodes. The novel finding in the third paper is that EF impairment is more strongly related to LGP than diagnosis (comparing MDD and schizophrenia). This finding is in line with the continuum hypothesis in psychiatry. In recurrent MDD, the level of performance on tests assessing EF seems to be inversely correlated with the level of saliva cortisol. Thus, this fourth study directly and indirectly gave support to the cortisol hypothesis. There is little evidence that unipolar major depression is uniquely associated with executive dysfunctions due to that 1) most components of EF are affected, 2) not all patients have executive dysfunctions, 3) executive dysfunctions are not specific to depression as they are also found in other mental disorders and in somatic disorders and 4) not all depressed patients have elevated levels of cortisol associated with executive dysfunctions. Future studies of the association between mental disorders and neurocognitive dysfunction should avoid restrictions resulting from imperfect diagnostic classifications for mental disorders, i.e. focusing on similarities in neurocognitive dysfunctions across psychiatric diagnoses rather than within one mental disorder at the time. Thu, 23 Nov 2006 22:58:59 GMT