| 1. |
- Aardal-Eriksson, Elisabeth
(författare)
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Salivary cortisol and posttraumatic stress reactions : methodological and applied studies before and after trauma
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The field of psychotraumatology has its roots in ancient history. During the past decades, the surveillance of the psychobiological background of reactions to and consequences of traumatic stress has made great progress and the complexity of the human stress response system stands out. The hypothalamic-pituitary-adrenocortical axis activity, modulated by various neuroimmunological substances, seems to play a major role in the stress response. However, there are still inconsistencies in explanations of relationships between biological and psychological changes following traumatic stress. Moreover, the matter of predictive factors for the development of posttraumatic morbidity is still in a speculative phase.The aims of the present thesis were to further develop a commercial serum cortisol radioimmunoassay (RIA) for determination of cortisol in saliva and to test its reliability, specificity and sensitivity as a biochemical assay. The saliva sampling procedures and sample storage stability were also to be tested. Further issues were to investigate determinations of salivary cortisol and serum prolactin in relation to selfratings of posttraumatic psychological distress and general psychological health. Possible predictive and concurrent validity of salivary cortisol as a biochemical marker for posttraumatic psychological distress were to be tested.Cortisol is present in saliva mainly in non-protein form, representing the free, biologically active fraction of the total plasma cortisol concentration. In a first phase of the present thesis, the commercial serum cortisol RIA was modified for determination of cortisol in saliva. The relation between salivary and serum cortisol concentrations was tested. Reference ranges at 8 AM and 10 PM for the salivary cortisol assay were established from 195 healthy subjects. Salivary cortisol concentrations were tested in relation to serum cortisol in estimating adrenocortical function during endocrine dynamic function tests in 37 patients and 13 healthy controls. In testing salivary cortisol as a marker for stress for fieldwork use, a screening study was performed on 66 male rescue workers. Salivary cortisol at 8 AM and 10 PM and serum prolactin were determined and general psychological health and posttraumatic psychological distress were estimated with the self-rating scales General Health Questionnaire, Impact of Event Scale and Posttraumatic Symptom Scale. These scales were used in the second phase of the thesis. Three applied follow-up studies were performed with sampling of salivary cortisol and self-ratings: (a) a study of 31 UN-soldiers five days, two and nine months after a mine accident; (b) a study of 145 UN-soldiers before, at return, and two and six month after a six month mission. (c) a study of 101 UN-soldiers six and twelve months after a six month mission with severe combat exposure.The results from the present thesis indicate that the modified method of salivary cortisol determination possesses sufficient precision, accuracy, sample storage stability and procedural advantages for laboratory, clinical and field application. Moreover, it possesses moderate predictive information and moderate to high concurrent validity as a biochemical marker for posttraumatic psychological distress.
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| 2. |
- Ahlgren, Ewa, 1959-
(författare)
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Cerebral complications after cardiac surgery
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cerebral injuty remains a major cause of morbidity and mortality after cardiac surgery. Previous studies have mainly focused on preoperative risk factors and intraoperative events but cerebral complications may also occur in the postoperative period. Cognitive impairment is common after cardiac surgery but the consequences of this complication for activities of daily life are less known. Safe driving involves a complex set of skills requiring preserved cognitive function. A substantial number of patients with heart disease are active drivers. The impact of postoperative cognitive dysfunction on driving performance, however, has not previously been investigated in this large patient group.In this thesis pre-, intra- and postoperative risk factors for focal cerebral complications were determined and the onset time of cerebral symptoms were evaluated in two cohorts of cardiac surgical patients, comprising 2480 and 3282 patients respectively. Data analysed were drafted from a clinical register and the surgical database of Linköping University Hospital Heart Center. Cerebral complication was delayed, i.e occurred after a free interval, in about one third of patients suggesting causes other than intraoperative events. Different risk factors were found for early and delayed cerebral complications suggesting different mechanisms of cerebral injury. Advanced age, preoperative hypertension, aortic surgery, prolonged cardiopulmonary bypass (CPB) time, intraoperative hypotension after completion of CPB, and arrhytlunia in the early postoperative period increased the risk for early cerebral complication. Female gender, diabetes, previous cerebrovascular disease, combined coronary artery bypass grafting (CABG) and valve surgery and arrhythmia on the thoracic ward increased the risk for delayed cerebral complication. Cognitive function and driving performance were evaluated in 27 patients before and 4-6 weeks after CABG. The patients underwent neuropsychological testing, an on-road driving test and a test in an advanced driving simulator. Twenty patients scheduled for percutaneous coronary intervention (PCI) served as controls. Complete data were obtained in 23 and 19 patients respectively. Furthermore cognitive function and driving performance in on-road driving of the 44 patients with complete tests before intervention were compared with controls of similar age without heart symptoms. Cognitive function and driving performance were already impaired in patients with coronary artery disease before intervention when compared with controls. After surgery 48% of the patients showed cognjtive decline compared to 10% after PCI. These patients also scored less in the on-road driving test to a greater extent than did patients without postoperative cognitive decline.
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| 3. |
- Alehagen, Siw, 1953-
(författare)
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Fear pain stress hormones during labor
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of the thesis were to develop a measure of fear during labor and to investigate women's experiences of fear and pain during labor and delivery as well as their levels of stress hormones. We also wanted to explore the associations between fear, pain, stress hormones and the duration of labor. Finally, we aimed to examine the relationships between pre-and postpartum fear, and fear and pain during labor.The measurement of fear was developed in two substudies. First we composed a list of 60 fear-related items and their contrasts and tested it in a group of 92 women in labor. After psychometrical analyses, 10 items were selected for the final scale. The scale was then tested in another group of 57 women in labor. Via semi-structured interviews the content of the items was documented and analyzed.Fifty-five nulliparous women participated in the investigation of women's experiences of fear, pain, levels of stress hormones and duration of labor. During gestation weeks 37-39, we measured levels of fear of childbirth, urinary catecholamines and salivary cortisol. During labor, hourly measurements were performed of fear, pain and levels of stress hormones. Finally, at two hours, two days and five weeks postpartum, fear of childbirth and stress hormones were measured.The questionnaire that measures fear during labor was called the Delivery Fear Scale (DFS). The DFS has an alpha coefficient of .8 and has good psychometric qualities in both nulliparous and parous women. It takes women in labor between 30 and 90 seconds to listen to and answer all the statements. We found that nulliparous women had higher fear during phase 1 of labor (cervix dilatation 3-Scm) than parous women. Fear during phase 1 of labor predicted the total amount of pain relief received during labor, but not the duration of remaining part of labor, nor the occurrence of instrumental vaginal delivery or emergency cesarean section.The results from the subsequently studies showed that there was an increase of the levels in stress hormones from pregnancy to labor. Epinephrine and cortisol increased more than 500% and norepinephrine approximately 50%. In women without EDA fear and cortisol increased throughout labor. In women with EDA cortisol did not increase, fear, pain and catecholamine levels first decreased after the administration of EDA but at the end of labor fear and pain increased. In phase 1, fear, but not pain, was more intensive in women who later subsequently received EDA than in those who did not. Fear and pain correlated positively during labor. A high level of epinephrine was associated with a shorter duration of phase 1 of labor. Postpartum fear of childbirth was higher in women who had received EDA during labor than in those who had not. Pre- and postpartum fear of childbirth correlated positively with fear but not with pain during phase 1 of labor.In conclusion, DFS is a new measure of fear during labor with good psychometric qualities. Childbirth is a stressful event associated with exceptionally high levels of stress hormones. In this study women's experiences of fear and pain were associated throughout labor. The administration of EDA heavily influenced the course of fear, pain and stress hormones. Women who later received EDA had higher scores of fear but not of pain early during labor than those who did not receive EDA. Late pregnant women who fear childbirth are prone to have a fearful delivery, as reported during the actual labor and postpartwn.
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| 4. |
- Anderson, Emma S., 1975-
(författare)
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The type IV Oligodendrocyte : experimental studies on chicken white matter
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In mammals, islet amyloid polypeptide (IAPP) is co-produced with insulin in pancreatic ß-cells. In the chicken, the expression of IAPP in the brain is more than 10-fold higher than in the pancreas. We made the fortuitous finding that a polyclonal rabbit antiserum raised against chicken IAPP did not recognise the immunogen, but labelled a subpopulation of oligodendroglia! cells in chicken white matter. The hitherto unknown antigen was called T4-O (Type 4 Oligodendrocyte) since it was localised to the Schwann cell-like Type IV oligodendrocyte of Del Rio-Hortega (1928). This formed a starting point for the present thesis, which is centred on the Type IV oligodendrocyte in chicken white matter.Biochemical analysis of chicken spinal cord showed that the T4-O molecule is a protein with a molecular weight of approximately 100 kDa and an isoelectric point of about 4. Further characterisation has not yet been possible.Immunohistochemical studies on frozen sections revealed that the white matter oligodendrocytes exhibit subpopulations expressing T4-O immunoreactivity strongly, weakly or not at all. Strongly T4-O immunoreactive (IR) oligodendrocytes are co-localised with thick myelinated fibres in the ventral (VF) and lateral funiculi of the spinal cord. A corresponding T4-O immunoreactivity is not found in the fish, the frog, the turtle, the rat and the rabbit.To find out when the T4-0 antigen first appears during development we examined sections from embryonic and post-hatching chicken spinal cords by immunohistochemistry. This showed that the T4-O molecule is first expressed in the VF at embryonic day (E)15, after which the number of IR cells increases with age. Oligodendrocytes cultivated in vitro without or with neurons do not develop a T4-O IR phenotype.These findings called for a closer analysis of the structural development of chicken VF white matter. Electron microscopic (EM) examination revealed a developmental sequence of events principally similar to the development of mammalian white matter, but with a more rapid time course. As seen in the electron microscope the first compact myelin has appeared by E12, when most oligodendrocytes are multipolar. By E15 it seems that these cells have developed a Type IV phenotype, possibly by eliminating some sheaths.Histochemical analysis of Vibratome sections showed that Marchi-positive myelinoid bodies are enriched in white matter areas containing many T4-O IR oligodendrocytes and many large myelinated axons.Examination of the three-dimensional (3D) anatomy of early VF oligodendrocytes in Vibratome slices after 04 labelling or after intracellular injection of a fluorescent dye revealed that these units indeed are Schwann cell-like, with a start length of around 50 µm. We also found that these sheaths expand very rapidly, reaching lengths exceeding 200 µm in three days (E12- E15). The 3D data conformed to our EM evidence that the early oligodendrocytes develop a unipolar Schwann cell-like Type IV anatomy through elimination of some sheaths.To my knowledge the present observations represent the first evidence for an oligodendroglia! heterogeneity in the chicken spinal cord. Differences among oligodendrocytes might, conceivably, explain why inherited disorders of myelin metabolism such as Krabbe's disease, affect some CNS areas more than others.
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| 5. |
- Andersson, Eva, 1946-
(författare)
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Vitamin A and ß-carotene metabolism and effects of UV irradiation in human keratinocytes and melanocytes
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Retinoids (vitamin A and its derivatives) are modulators of proliferation and differentiation. Both retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) can be converted to retinoic acid (RA) and 3,4-didehydroretinoic acid (ddRA), ligands for the nuclear receptors, which induce gene transcriptions. A perturbed ROH metabolism is observed in several dermatoses and iu non-melanoma skin cancer. Dietary ß-carotene has been considered to play a critical role in the natural defence against cancer. Whether ß-carotene is converted to ROH in the skin has been debated.We have investigated ß-carotene and retinoid metabolism, retinoid binding proteins and retinoid receptors in human keratinocytes (KCs) and melanocytes (MCs) in vitro. Similar studies of vitamin A have been done in human malignant epithelial cells (HeLa) and malignant melanoma cells. The influence of ultraviolet radiation (UVR) on retinoid metabolism and receptor expression was specially focused upon this thesis. KCs and MCs contained high concentrations of ROH, ddROH, while HeLa- and melanoma cells contained lower levels. KCs contained the highest level of the retinoid-binding proteins CRBP I and CRABP II compared to MCs, HeLa and melanoma cells. High CRABP II levels showed a correlation with the ability to accumulate ddROH. In MCs, CRABP I was highly expressed, but in melanoma cells CRABP II dominated. The difference between MCs and melanoma cells in receptor levels was most pronounced for RARß, which was highly expressed in melanoma cells. Such dissimilarities between benign and malignant MCs might play a role in differentiation and growth regulation. The uptake of [3H]ROH, [3H]RA and ß-carotene was significantly higher in MCs than in KCs. We were able to demonstrate that [14C]ß-carotene was converted to [14C]ROH in both these cell types. This suggests that this local storage of ß-carotene might serve as au alternative supply for vitamin A in the skin.A moderate dose of UVR reduced the concentration of ROH, ddROH and [3H]RA in KCs and MCs by 20-50%. The concentration returned to starting levels in 1-2 days, and could be explained by a retarded metabolism of RA, the biologically most active metabolite. When KCs and MCs were exposed to UVR, the mRNA and protein levels of the three nuclear retinoid receptors (RARα, RARγ and RXRα) decreased rapidly. In MCs these levels were close to normal 3 days postirradiation. In KCs only the RARα mRNA and protein levels returned to baseline within 3 days. This thesis has increased our knowledge of the effects of UVR on retinoid metabolism and retinoid receptors in human cells. Further studies are needed to understand the role of ß-carotene and retinoid signaling in UV induced skin cancer.
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| 6. |
- Aniansson Zdolsek, Helena, 1961-
(författare)
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Maturation of T-lymphocytes and monocytes in children in relation to development of atopic disease
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund: Atopiska sjukdomar har ökat i västvärlden under de senaste årtiondena. För att förstå den bakomliggande mekanismen vid sensibilisering mot allergen behöver vi förbättra vår kunskap av T-lymfocyters och monocyters utmognad hos små bam.Mål: Att prospektivt studera utmognaden av T-lymfocyter och monocyter hos bam som senare utvecklade atopisk sjukdom.Material och metoder: 170 barn med och utan atopisk sjukdom i familjen följdes från födelsen till 18 månaders ålder, och 38 av dessa följdes också upp vid sju års ålder. Förekomst av atopisk sjukdom under uppväxten(= kumulativ sjukhistoria) registrerades. En hudpricktest (SPT) utfördes vid 18 månader och vid sju års ålder. Markörer för ytreceptorer på T-celler (CD2, 3, 4, 8, 28) studerades med hjälp av flödescytometrisk teknik på alla bam vid födelsen och vid 18 månaders ålder. Dessa markörer studerades också vid 3, 6 och 12 månaders ålder i en undergrupp om 78 barn med stark familjär ärftlighet för atopisk sjukdom, eller avsaknad av sådan. Vid 18 månaders ålder deltog 54 barn, 29 icke-atopiska och 25 atopiska, i en funktionell T-cellsstudie. Proliferation av perifera mononukleära celler i blodet (PBMN celler) studerades med inmärkning av 3H-tymidin efter stimulering med anti-CD3 eller phytohemagglutinin (PHA). Anti-CD3 inducerad cytokin produktion (IL-4, IL-5, IL-6, IL-10, IL-13 och IFN-γ) rutalyserades med ELISA teknik (enzyme-linked immuno sorbent assay). Vid sju års ålder följdes 38/54 bam upp och IL-12 svaret hos PBMN celler studerades efter att stimulering med IL-2, IL-12 eller båda. Uttrycket av 1L-12Rß2 mRNA mättes med real-tids PCR (polymerase cltain reaction), medan cytokin-nivåer IL-5, IL-10 och IFN-γ mättes med ELISA. På 76 barn studerades monocyt-mru·kören CD14 med flödescytometrisk teknik, lösligt CD14 i serum (sCD14) med ELISA och total-nivåer av immunglobulin E (lgE) med UniCAP® vid födelsen, 3, 6, 12 och 18 månaders ålder. Vid sju års ålder rutalyserades också sCD14 och total-IgE hos 38 barn.Resultat: Vid 18 månaders ålder var 118/170 barn icke-atopiska och 31/170 hade utvecklat atopisk sjukdom. CD4 FI på T-hjälpar (CD3+CD4+) celler var lägre vid födelsen och vid 3 månaders ålder hos barn med en atopisk kumulativ sjukhistoria vid 18 månaders än hos ickeatopiska. Atopi var också förenat med en låg andel av CD2+ lymfocyter vid 18 månaders ålder. Vid samma ålder hade barn med kumulativ sjukhistoria och en positiv SPT lägre CD2, liksom lägre CD3 FI på pan T (CD3+CD45+CD14-) celler och högre CD28 FI på CD2+CD8+CD28+ celler. Atopisk sjukdom vid 18 månader var förenat med högre nivåer av anti-CD3 inducerad IL-5 sekretion och SPT- barn med atopisk sjukdom producerade högre nivåer av IL-l O än SPT + barn. Kvoten av IL-4/ IL-l O och IL-4/ IFN-γ var högre hos barn med förhöjda nivåer av total IgE. Barn med atopisk sjukdom och atopiska luftvägssymptom uppreglerade uttrycket av IL-2 inducerad IL-I2Rß2 mRNA mindre än icke-atopiska brun vid sju års ålder. De hade också en lägre IL-2 och IL-12 inducerad IFN-y sekretion. Vidare var sCD14 lägre vid sju års ålder hos barn med en atopisk kumulativ sjukhistoria, än hos ickeatopiska barn. Detta mönster observerades också vid 3 och 18 månader hos SPT+ barn med kumulativ atopisk sjukhistoria vid 18 månaders ålder jämfört med SPT- icke-atopiska barn. Dessutom hade barn med mycket allergi i familjen lägre nivåer av sCDI4 vid 3, 12, och 18 månader och vid 7 års ålder än bam utan allergi i familjen.Sammanfattning: Utmognaden av T celler och funktionen av dessa skiljer sig mellan atopiska och icke-atopiska barn. IL-12 svaret hos barn med atopiska luftvägssymptom och höga nivåer av total-IgE är reducerat. Sammantaget kan detta bidra till ett T-hjälpar 2 devierat humunsvar vid atopisk sjukdom. Atopiska barn har lägre nivåer av sCD14. De låga nivåerna kan möjligen vara en konsekvens av familjär atopisk ärftlighet/atopisk sjukdom och kan kanske också avspegla en minskad förmåga att svara på mikrobiella signaler hos atopiska individer.
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| 7. |
- Cedergren, Marie, 1963-
(författare)
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Epidemiological studies of congenital heart defects in the Southeast region of Sweden
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the most recent analysis of Swedish data on congenital malformations, it appeared that in the county of Östergötland, the prevalence of infants with a diagnosed congenital malformation was higher than in the rest of the country. This observation initiated an effort to make a more complete identification of all infants born with a congenital malformation in that county and to compare it with the other two counties in the Southeast region of Sweden (Jönköping and Kalmar), utilising all the relevant Swedish medical health registers available. A total of 10,171 infants with a congenital malformation of any type were identified in the region: 4,698 infants in Östergötland county (6.2%), and 5,473 in the reference counties (5.4%). A 15% excess malformation risk in Östergötland compared with the two reference counties. Various validations of the register data were undertaken and different types of error were detected. Limb reduction defects seemed to occur more often in Östergötland county and there was an increased risk of cardiovascular malformations in Östergötland county (22%).The next step comprised an exploration of putative risk factors for cardiac defects in the area. Maternal body mass index (BMI) >29 was found to be a significant risk factor for cardiac defects. Maternal diabetes mellitus and maternal use of antiepileptics were associated with an increased risk of cardiac defects in the offspring.To explore if the pregnant women in Östergötland county differed from the women in the reference counties, a comparative analysis of potential risk factors was performed. The only single putative risk factor that could contribute to the excess risk of cardiac defects in Östergötland county was matemal residency in a rural district. Notably, nearly all the potential risk factors studied i.e. spontaneous abortions, involuntary childlessness, maternal disease, high maternal body mass index, matemal medical during use and alcohol use in early pregnancy, parental employment and paternal age were stronger in Östergötland county compared to the reference area. A conceivable explantation is that one or more unidentified factors could activate prevalent and weak teratogenic risk factors for cardiac defects.Drinking water could be such a factor. By using a geographical infmmation system (GIS) it was possible to obtain individual data on drinking water characteristics. An increased tisk of a congenital cardiac defect seemed to be associated with the chlorination procedure, in particular the use of chlorine dioxide, and with increasing total trihalomethane concentration.
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| 8. |
- Christensson, Lennart, 1952-
(författare)
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Malnutrition in elderly people in need of municipal care : assessment and intervention
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to describe nutritional status in elderly people at the time of entering municipal care, to evaluate nutritional assessment techniques and to investigate the effect of a nutritional care plan. Furthermore the aim was to investigate the staffs' attitudes towards nutritional nursing care. A total of 261 residents, mean age 84 years (range 65-103 years), admitted to a community resident home in a municipality in the south of Sweden were included. At the same municipalities, 151 nursing staff responded to an attitude scale on two occasions with one year between.During the first or second week after admission nutritional status was assessed using a combination of anthropometry and serum protein measurements as the criterion to define protein- energy malnutrition (PEM). This combination constituted the standard criterion when validity of the Subjective Global Assessment (SGA) and the Mini Nutritional Assessment (MNA) were evaluated. In 40 residents assessed as non-PEM on admission health problems were measured by the Nottingham Health Profile (NHP). To investigate the effect of a nutritional programme energy intake, anthropometry, serum protein measurements and functional capacity were assessed continuously during a five months period in 11 residents assessed as being PEM on admission. The nutritional programme consisted of meals based on individual energy requirements. An attitude scale was developed and used in order to measure whether the attitudes of nursing staff towards important issues within eating and nutrition changed after implementation of an educational programme.On admission, 33% of 261 elderly people were assessed as being PEM. The frequency of pressure sores or leg ulcers, psychological stress or acute disease in the previous 3 months, reduced fluid intake, deteriorated appetite, reduced mobility, need of help during meals and gastrointestinal symptoms were significant higher in residents assessed as PEM compared with residents assessed as non-PEM. Both SGA and MNA proved to be useful in detecting residents objectively assessed as PEM. NHP, measuring health problems, showed power to predict residents at risk of malnutrition. Anthropometric measurements, serum protein concentration and functional capacity increased significantly in 11 residents assessed as PEM after 3 months on the individualised care programme. Nutritional education and implementation of a nutritional programme did not change the attitudes of nursing staff towards important nutritional issues.In conclusion, at the time of entering municipal care a high frequency of residents assessed as PEM or at risk of PEM was found. The SGA and MNA were shown to be useful tools in detecting resident in need of nutritional attention. For early detection of residents at risk of malnutrition, measurement of health problems added important information. An individualised nutritional care programme was one useful approach to the improvement of nutritional status and functional capacity in residents assessed as PEM on admission. On the whole, nursing staff responded with positive attitudes towards nutritional nursing care. Nutritional education and implementation of a nutritional programme did not significantly change their attitudes.
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| 9. |
- Ekman, Bertil
(författare)
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IGF-I in growth hormone deficiency and in type 1 diabetes
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Both GH-deficiency and type 1 diabetes are associated with low IGF-I levels. The aim with our studies was to develop a dose titration model to obtain physiological IGF-I levels in growth hormone deficiency and to evaluate the relationship between glycaemic control and IGF-I in diabetes. First we established reference values for insulin like growth factor-I (IGF-I) and insulin like growth factor bindingprotein-1 (IGFBP-1) from 101 women and 101 men randomly selected from the population registry. No gender differences in IGF-I levels were fmmd. IGF-1 decreases with advancing age in both sexes, whereas IGFBP-1 increases with age.Titrating the GH dose according to population based reference values of IGF-I might be a way to obtain a fairly physiological substitution dose of GH. We hypothesised that a safe and probably effective maintenance dose of GH should increase IGF-I to the mean or slightly below the mean according to age adjusted reference levels. Eighteen adult hypopituitary patients with severe GH deficiency were titrated in steps, according to age adjusted IGF-I levels, to an individual dose of recombinant GH. For comparison 17 untreated healthy control subjects were evaluated. Similar IGF-1 levels armmd the mean for corresponding age were obtained in both sexes, but the maintenance median GH dose was more than twice in the women compared to men. The :individual dose differed markedly and elderly patients needed lower GH doses due to unchanged GH-sensitivity. Six months on the maintenance GH dose induced changes in blood-glucose, lipids, and insulin sensitivity index, indicating increased insulin resistance, which compared with the controls, were a normalisation. No major changes were seen in the variables of the renin-angiotensin-system. A significant increase in atrial natriuretic peptide seems also to be a normalisation if compared with the controls. The patients had less muscle strength and endmance at baseline compared with the controls and increased the muscle strength and endmance about 10 % after GH-substitution, an effect associated with the increase in IGF-I.Paradoxically circulating IGF-I is decreased in type 1 diabetes despite increased GH levels. We studied 134 adult patients with type I diabetes (aged 20-60 years), without endogenous insulin secretion, and found that circulating IGF-I were decreased to about 70 % of the values in the reference population. No con·elation between glycaemic control and IGF-I levels was found.To conclude the GH dose obtained when normalising circulating IGF-I according to population-based IGF-I levels, depends on GH-sensitivity (gender) and the IGF-1 level aimed for (age). In comparison with matched controls several OR-dependent variables are improved. In type 1 diabetes, our results suggests that the low IGF-I levels are independent of glycaemic control, and can not be corrected with subcutaneous insulin substitution.
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| 10. |
- Esamai, Fabian
(författare)
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Cerebral malaria in children in the highlands of Kenya : Aspects of pathogenesis and clinical presentation
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Malaria affects over 300 million persons in the world each year with a mortality of close to 2 million. In developing countries malaria has been endemic in the lowlands for centuries with no occurrence in the highlands above 2000 metres above sea level. This pattern has changed over the last decade whereby malaria is occurs in epidemics with a high morbidity and mortality among the inhabitants of the highlands especially children and pregnant women. Eldoret and its environs in Kenya is a highland area with an altitude of 2300 metres above sea level where malaria was rare up to the late 1980s. Since 1988 malaria occurs in epidemics in this region with a high prevalence of severe malaria especially cerebral malaria(CM). This led to the conduct of stndies that fonn the basis of this thesis with the aim of delineating aspects of pathogenesis and the clinical presentation of CM in the Western highlands of Kenya.Materials and Methods: Cross sectional, retrospective and prospective studies were conducted to study the prevalence of malaria among inpatients at the Moi Teaching and Referral Hospital (MTRH); to describe the clinical presentation of CM in the highlands; to compare temperatures in CM and uncomplicated malaria(UM) cases and to assay the serum tumour necrosis factor alpha (TNFa) and transforming growth factor beta (TGF-13)1 levels in these patients.A total of 4 720 children were retrospectively and prospectively studied over an 18 month period (1991-1993) to establish the top 20 diseases at the MTRH. This was followed by a prospective study of 23 CM and 12 UM cases in 1997. All the presenting features of the cases with CM were tabulated on admission and analysed so as to establish the clinical presentation of CM in this region and compare this to the standard as described by the World Health Organisation (WHO). A comparison was made between the brain, core and skin temperatures of the CM and UM cases with normal children acting as controls.This was a follow up of a similar stndy in 1993 that compared core and skin temperatures between measles, CM and UM with normal children as controls. Serum TNF-a and TGF-131 levels were assayed and compared among the CM and UM patients in the 1997 study and included the assay of cerebrospinal (CSF) TNF-α and TGF-β1 in CM.Results and conclusions: Malaria accounted for 3 3% of all admissions over the study period with a case fatality rate of 2.2% and a mortality rate of 10.7%. Most children with CM were aged 3-10 years and were of good nutritional status. They presented in coma, with fever, headache, convulsions and hyperparasitaemia and with a short duration of illness of less than 3 days. Severe anaemia and hypoglycaemia were not common features. Malaria is the leading cause of morbidity in the children stndied. CM in the highlands presents as that seen among non-immunes. There were no differences in brain, core and skin temperatures between the CM and UM patients. The brain temperature was however always lower than core temperature even in normal controls with brain temperature having a positive correlation with core temperature as the body temperature rises. Thus, the role of fever in the pathogenesis of CM is still unclear The serum TNF-α and TGF-β1 levels were the same in UM and CM cases with TNF-α and TGF-β1 having an inverse relationship to each other. Patients with deeper levels of coma had higher levels of TNF-α and lower levels of TGF-β1.
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