| 1. |
- Pettersson, Ulrika, 1970-
(författare)
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Bone mass in the young athlete
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bone mass and bone size accumulate during childhood and adolescence and peak in the twenties. The obtained peak bone mass has been suggested to be a major determinant of bone mass even in the very elderly. Although, genetic factors are the main determinants, environmental and lifestyle factors also play a crucial role in modulating maximal bone mass. Assessing these lifestyle factors would be of great importance for the intervention strategies against osteoporosis. The first aim of this thesis was to compare the bone mass and bone size in male and female young adults on a high level of physical activity with males or females on a low level of physical activity. Furthermore, it also aimed to investigate the influence of pubertal maturity, menstrual disturbances, and different body constitutional factors on bone mass and size during adolescence and young adulthood. The female activity groups consisted of cross-county skiers, soccer players, and rope skippers. Compared to their age-matched inactive controls, all these athletic groups demonstrated a significantly higher bone mineral density (BMD) at those sites subjected to the sport-specific loading. Rope-skipping, a very high impact activity was associated with a higher bone size, preferentially in the lower extremity, suggesting an effect of weight-bearing activity also on bone geometry. The effect of menstrual disturbances was evaluated in a group of long-distance runners, where amenorrheic runners had significantly lower BMD in both trabecular and also cortical bone in the lower extremity compared to eumenorrheic runners, suggesting that weight-bearing activity cannot compensate for the shortfall of reduced estrogen levels. The male activity groups consisted of ice hockey players and badminton players. Compared to their age-matched controls, both athletic groups demonstrated a significantly higher BMD at those sites subjected to the sport-specific loading. Especially badminton was associated with a high BMD, suggesting that physical activity, including jumps in unusual directions has a great osteogenic potential. The main determinants of BMD in both male and females were, except for type of physical activity, activity, muscle strength, height, and different body constitutional factors. However, the relationships with muscle strength and body constitution were somewhat weaker in the athletic groups, especially in the males, indicating that impact forces may be of greater importance in regulating bone mass in highly trained athletes. Yet bone size was largely determined by parameters related to body size and less strongly to physical activity. In a prospective study on adolescent boys, the changes in bone mass during late puberty were mainly accounted for by growth and development, including height and pubertal maturation, and less to physical activity level. Thus, the osteogenic effect from physical activity seems to be of importance for bone mass achievement predominantly before late puberty.
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| 2. |
- Reuterskiöld, Christina
(författare)
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Language Processing and Contextual Influence. A study of Swedish preschool children with language impairment.
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Language Processing and Contextual Influence A Study of Swedish Preschool Children with Language Impairment The aim of the present work was to study different types of contextual influence on language performance in a variety of tasks: repetition of nonwords, narration, understanding of idioms and picture naming in a group of Swedish preschool children with language impairment (LI). The stress pattern of words and nonwords was found to have an impact on the repetition performance of the participants. Furthermore, nonword repetition was found to be linked to expressive language skills, particularly phonological developmental level. Different types of genres, that is conversation and narration, led to differences in aspects of language production such as fluency and grammatical structure. We also found that the relative level of language comprehension was important for the ability to provide a story with several content units as well as to only include aspects considered relevant for the listener and the task. It was shown that preschool children with LI do not interpret idioms literally but they have difficulties defining them. Idiom understanding was linked to performance on a theory of mind task, measures of semantic-lexical skills as well as receptive grammar. In the final study a sentence prime significantly increased naming speed in children with LI. There was a tendency that children who benefitted from the prime were the individuals with relatively good scores on some of the verbal measures. Assessment tools that incorporate dynamic aspects of processing need to be developed for clinical use. A dialogistic perspective could provide additional information when assessing children with LI.
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| 3. |
- Ekelund, Anders
(författare)
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Detection and haemodilutive treatment of cerebral arterial vasospasm and delayed ischaemia after Aneurysmal Subarachnoid Haemorrhage
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with cerebral arterial vasospasm and ischaemia, a serious complication after aneurysmal subarachnoid haemorrhage. Firstly is the noninvasive transcranial Doppler ultrasound and transcranial cerebral oximetry techniques evaluated in detecting cerebral arterial vasospasm in clinical practice. Patients were examined during first 14 days after the bleed. Flow velocities in normo- versus hypertensive patients were also compared. Secondly is the effect in blood viscosity, cerebral blood flow and cerebral oxygen delivery rate evaluated during the commonly used haemodilutive therapy for vasospasm. Haematocrit after colloid infusion was compared with controls. Both global and regional cerebral blood flow was measured after iso- and hypervolaemic haemodilution. Transcranial Doppler ultrasound used daily is a valuable non-invasive bedside method to detect an increased risk for vasospasm. Especially when there is a rapid increase in mean flow velocity during 24 hours. However, in patients with verified arterial hypertension even a moderately increased mean flow velocity may indicate vasospasm. Transcranial cerebral oximetry may be useful as a complement to transcranial Doppler ultrasound as a correlation between reduced cerebral saturation and increased mean flow velocity seem to exist. There is a spontaneous haemodilution after subarachnoid haemorrhage as haematocrit is lowered irrespective of haemodilutive therapy or not. Haemodilutive therapy alone may therefore not be beneficial for SAH patients. Isovolaemic haemodilution does not improve cerebral oxygen delivery although global cerebral blood flow and transcranial Doppler mean flow velocity increases. Nor is hypervolaemic haemodilution beneficial for patients with vasospasm as the increased CBF is counteracted by a reduction in oxygen delivery to the brain.
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| 4. |
- Bergdahl, Anders
(författare)
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Altered vascular responses in experimental congestive heart failure
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Congestive heart failure is accompanied with increased circulatory levels of several vasoregulatory neurotransmitters and hormones which affect the outcome of this disease. In this thesis the blood levels of several vasoactive peptides in humans with congestive heart failure and their effects on the vasculature by the use of an animal model of heart failure were studied. Patients with congestive heart failure had increased levels of noradrenaline (NA), adrenaline (A), neuropeptide Y, atrial natriuretic peptide (ANP) and antidiuretic hormone. The increased levels of ANP and NA correlated to the survival time in patients with congestive hart failure. Increased levels of NA and A were also found in the animal heart failure model. The passive elastic and active contractile capacity of small mesenteric arteries were attenuated in heart failure animals. Ca2+-mediated and KCl -induced contractions were attenuated in heart failure vessels, an effect due to alterations of a-adrenoceptors. The contractile responses of isolated vessel segments to agonists of the sympathetic nervous system were altered, especially the a2- adrenergic receptor, which mediated an attenuated response in several vascular beds, both in vivo and in vitro, in heart failure animals. The sympathetic co-transmitter neuropeptide Y (NPY) enhanced the response to NA in human omental arteries via the Y1 receptor and this receptor was involved in the modulation of the response to endothelin (ET) -1, U46619 and 5-HT in heart failure vessels. NPY-induced potentiation of ET seem to be mediated by a receptor different from the NPY Y1 type. Endothelin was found to be less potent in large conductance arteries in heart failure while the reverse was noted in small mesenteric arteries. The response mediated through the smooth muscle endothelin B receptor was altered since inhibition of this receptor in endothelium-denuded arteries induced a leftward shift of the concentration-response curve in heart failure but not in control animals. The dilatory response to calcitonin gene-related peptide was attenuated in several arterial beds in heart failure rats. It is concluded that the animal model is suitable for studying the effects of neurotransmitters in heart failure and correlates with findings in humans. Further, several receptor alterations are induced which might influence the outcome of this condition.
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| 5. |
- Bulow, Birgitta
(författare)
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Cardiovascular mortality and morbidity in hypopituitary patients and metabolic effects of growth hormone treatment
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Premature atherosclerosis, cardiovascular risk factors and increased cardiovascular mortality have been shown in patients with hypopituitarism on conventional hormone treatment, but without growth hormone (GH) replacement. The aims of paper I-III were to investigate separately the risks for cerebrovascular and cardiac mortality as well as the incidence of cardiovascular disease in patients with hypopituitarism and to assess the long-term prognosis for patients with craniopharyngioma. GH replacement has been associated with an impairment of glucose tolerance and the objectives of paper IV-V were to investigate whether individualized GH replacement therapy could avoid such a deterioration. There was a 1.75-fold increased cardiovascular mortality in 344 hypopituitary patients operated for a pituitary tumour compared to the general population. The risk for death in cerebrovascular disease was higher than for cardiac disease and females had a higher risk increase than males. A survival analysis of 60 patients operated for craniopharyngioma showed a more than 3-fold increase in cardiovascular mortality compared to the general population. There were no protective effects of radicality at surgery or radiotherapy on survival in patients with craniopharyngioma. Increased incidence of cardiovascular disease and increased prevalence of cardiovascular risk factors, such as lower degree of physical exercise, higher WHR, lower HDL-cholesterol and higher LDL:HDL ratio were observed in 33 hypopituitary females compared to a control group matched for sex, age, smoking habits, educational level and residence location. The increased cardiovascular mortality and morbidity could not be explained by inadequate treatment with corticosteroids, thyroid hormones or sex hormones alone. Unsubstituted GH deficiency (GHD) is likely to be a more important contributing factor. Individualized GH treatment to ten patients with childhood onset GHD caused a significant decrease in fat mass, but no impairment was observed in glucose tolerance during euglycemic conditions. The GH dose was adjusted after serum insulin-like growth facor-I (IGF-I) levels, which could be a useful method for monitoring GH treatment in adults with childhood onset GHD. During hypoglycemia, GH therapy caused an increase in insulin resistance, which could not be explained by changes in the counterregulatory hormones or serum IGF-binding protein-1.
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| 6. |
- Hauge, Truls
(författare)
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The upper gastrointestinal tract in chronic alcoholics
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Gastrointestinal symptoms such as dyspepsia, diarrhoea, and nausea are often seen in alcoholics. The causes are not clear. The stomach and upper small intestine are exposed to high alcohol concentrations. Yet, the majority of alcohol abusers do not exhibit macroscopic abnormalities at upper gastrointestinal endoscopy, although histological and electron microscopic (SEM) changes have been described. However, there are only scanty and contradictory data on this subject so far. Aim: In order to extend our knowledge in this field, we have studied a fairly large number of chronic alcoholics with respect to GI symptoms and endoscopic findings. Moreover we also explored the occurrence of Helicobacter pylori and mucosal bacterial growth, electron microscopical changes in duodenal mucosal morphology and induction of gamma-glutamyl transferase (GGT), intestinal alkaline phosphatase (IAP) and neuropeptides in the duodenal mucosa. Materials and methods: Twenty-four chronic alcoholics who were admitted to hospital for detoxification were investigated using an interview, upper gastrointestinal endoscopy with biopsies, and laboratory tests. The mean daily consumption of alcohol during the weeks before admission was 338 g/day (102-680). The control groups consisted of 12–33 patients referred for upper gastrointestinal endoscopy because of dyspepsia of the ulcer or reflux type, but who felt healthy otherwise. In addition, an interview was carried out as well as laboratory tests including serum CDT and serum GGT. The alcohol consumption was less than 40 g/week. Results: Twenty-one of 24 alcoholics had gastrointestinal symptoms on examination: 15 had abdominal pain/dyspepsia, 12 had diarrhoea, and 6 had nausea. There were not more patients with H. pylori infection in the alcohol group compared to controls and prevalence studies. Endoscopy showed no difference between the groups. Histology showed a slightly reduced villus index in duodenal biopsies, as well as ultrastructural changes (SEM). There were significantly more bacteria in the gastric mucosa in alcoholics than in controls (p<0.05). IAP and GGT levels were significantly higher in duodenal biopsies in the alcohol group (p=0.001, p<0.0001). The density of all the peptidergic nerve fibres in the duodenal mucosa exhibited a moderate general increase, but none of the peptides was selectively and strongly influenced. The numbers of glucagon and GIP cells in the duodenal mucosa were slightly increased in the alcohol group (p=0.02). Summary and conclusion: Chronic alcoholics often have gastrointestinal symptoms. They frequently exhibit mucosal bacterial overgrowth. Electron microscopic morphological changes are commonly found. GGT and IAP in the duodenal mucosa are increased. An alteration in the peptidergic nerve system as well as in some endocrine cells could be observed. Thus, in spite of scarce endoscopic findings in the upper GI tract, chronic alcoholics do show definite alterations in several respects as mentioned above.
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| 7. |
- Zhou, Li
(författare)
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Sources of Arachidonic Acid in Platelets, Bone, Marrow and Gastrointestinal Tract
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study investigates pathways by which the eicosanoid precursor pools in the platelets, bone marrow and the gastrointestinal (GI) mucosa are acquired and regulated, and in this context some aspects on the interaction between triglyceride (TG)-rich lipoproteins and platelets. 1. Platelets take up chylomicrons (CM) in vitro, the main part being sequestered in open canalicular system and not degraded, but do not exhibit any receptor mediated uptake and degradation of chylomicron remnants (CMR). Although CM, CMR and Intralipid affect agonist-induced platelet aggregation in vitro, CMs and CMRs are not an arachidonic acid (AA) source for platelets. The binding of prothrombin and protein S to postprandial TG-rich lipoproteins increased more after a meal rich in saturated fat than after a linoleate (LA) rich meal, which might increase platelet induced activation of these factors. 2. In rats plasma 2-arachidonyl-lysophosphatidylcholine (2-AA-LPC) supplies AA to several extrahepatic tissues, the quantitative importance being large in case of the small intestine. In guinea pigs, local desaturation-elongation of LA taken up as plasma free fatty acids (LA-FFA) is a major AA source. Bone marrow cells including megakaryocytes and the mucosa of GI tract produce much more AA than is exported from the liver. Therefore, we suggest that uptake and local interconversion of plasma LA-FFA and uptake of plasma 2-AA-LPC are two important alternative pathways for the supply of AA to extrahepatic tissues. Since platelets do not convert LA to d6-desaturase products, it is suggested that the build up of AA pools may be an integral part of the platelet formation in the bone marrow. 3. Fasting increases the rate of uptake and interconversion of plasma LA-FFA in both liver and extrahepatic tissues. The increase of plasma FFA concentration enhances the tissue uptake and this is linked to an increased rate of local interconversion of plasma LA-FFA. The concentration and composition of the plasma FFA pool as well as the regulation of desaturases activity in extrahepatic tissues during fasting is important determinants of eicosanoid precursor formation. 4. Our results challenge the common view that the liver is the main site of formation of AA which is then transported to other tissues mainly by lipoproteins. Our animal model can be used to study the rates of fatty acid desaturation and acylation in relation to enzyme activities and substrate availability in vivo.
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| 8. |
- Al Rayyes, Osama
(författare)
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Post-transplantation Hypercholesterolaemia
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The multidrug regimen, cyclosporine, corticosteroids, and azathioprine, is used in transplantation centres to prevent organ rejection. Several clinical studies have shown that cyclosporine and corticosteroids to cause increases in low density lipoprotein (LDL)-cholesterol, with subsequent development of atherosclerosis. The overall objective of the studies upon which this thesis is based was to investigate the aetiology and management of hypercholesterolaemia in transplanted patients. The highly differentiated HepG2 hepatocytic cells were used in tissue culture to study LDL catabolism. The results show cyclosporine and hydrocortisone (as an example of corticosteroids), either alone or combined, to decrease LDL catabolism due to a decrease in the synthesis of mRNA of the LDL receptor. 3-hydroxy-3-methylglutaryl CoA reductase inhibitors can compensate for the reducing effect of cyclosporine and hydrocortisone. Two of the major complications of corticosteroid therapy are impaired glucose tolerance and Cushing's syndrome, associated with a great risk of complication by insulin-resistant non-insulin dependent diabetes mellitus (NIDDM). Moreover, nephropathy is one of the long-term complications of diabetes mellitus, and associated with a risk of progression to renal failure necessitating transplantation. Troglitazone, a thiazolidinedione compound that is used in the treatment of insulin- resistant NIDDM, was examined to investigate its effect on LDL catabolism. The results showed troglitazone to increase LDL catabolism by increasing the synthesis of the LDL receptor mRNA. This effect may be due to an activation of peroxisome proliferator-activated receptor gamma (PPARg), as troglitazone is one of the PPAR gamma activators. Non steroidal anti-inflammatory drugs (NSAIDs) have recently been shown to activate PPARs but they also inhibit the release of different inflammatory mediators and cytokines. The results obtained in HepG2 cells , showed NSAIDs, particularly flufenamic acid and indomethacin, to enhance LDL catabolism by increasing the synthesis of LDL receptor mRNA. This effect may be due to an activation of PPARs. The conclusion to be drawn from the studies is that, after organ transplantation, cyclosporine and hydrocortisone decrease hepatic LDL receptor activity, which can be counteracted by HMG-CoA reductase inhibitors (statins). Also troglitazone, due to its increase in hepatic LDL receptor activity, should be well suited for use after organ transplantation of diabetic subjects. In addition to their anti-inflammatory effects, NSAIDs might be useful in controlling hypercholesterolaemia induced atherosclerosis. The hypocholesterolaemic effect of troglitazone and NSAIDs might provide a theoretical basis for the development of new strategies for the treatment of hypercholesterolaemia.
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| 9. |
- Elneihoum, Ali Mohamed
(författare)
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Ischemic Cerebrovascular Disease: Risk Factors and Outcome Predictors with special reference to the role of leukocytes and inflammatory mediators
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ischemic cerebrovascular disease (CVD) is usually a consequence of atherosclerosis and is the commonest cause of stroke. The identification of risk factors and outcome predictors and the initiation of preventive measures constitute the cornerstone of efforts to reduce the risk of stroke and improve outcome. The trend for long-term outcome after stroke and the predictors of this outcome were evaluated in the light of data accumulated during the first four years after the founding of the Malmö Stroke Registry in 1989. Early predictors of ischemic CVD were studied in middle-aged, apparently healthy individuals, from the Malmö Prevention Project cohort. Since leukocytes are believed to play important parts regarding the risk and outcome of ischemic CVD, their possible involvement was the focus of special interest in this study. Although stroke incidence remained unchanged during the first four years of the Malmö stroke registry (1989-92), there was a trend toward a decline in the long-term recurrence and mortality rates following stroke. The long-term outcome predictors were evaluated. The age-standardized recurrence-free survival rate differs significantly between different residential areas in the city. In middle-aged, apparently healthy individuals, apart from traditional risk factors, a history of calf pain while walking (OR 1.9; p=0.002), a high serum uric acid level (OR 1.2; p<0.05) were found to be significant predictors of future ischemic CVD. In subjects with asymptomatic atherosclerosis (n=156), plasma levels of leukocyte activation markers neutrophil protease 4 (NP4), neutrophil gelatinase associated lipocalin (NGAL), tumor necrosis factor a (TNFa) and soluble TNF receptor-1 (sTNFR-1) were related to atherosclerosis risk factors (age, blood pressure, history of hypertension, and smoking). Patients with acute ischemic CVD (n=120) manifested higher plasma levels of NP4, NGAL and sTNFR-1 than did controls. During 4-year follow-up of patients with ischemic CVD (n=144) plasma levels of leukocyte activation markers at the time of acute cerebral ischemia, NGAL (OR 3.6; p<0.05) and sTNFR-1 (OR 2.0; p<0.01), were independent predictors of cardiovascular mortality. In conclusion, despite the observed trend of improving long-term outcome following stroke, the burden of this disease is still high. The observed variation of the long-term stroke free survival rate between different residential areas of the same city might be due to intra-urban differences in risk factor exposure or might indicate the importance of sociodemographic factors vis-à-vis long-term prognosis after stroke. Apart from traditional factors predicting ischemic CVD, the routine use of a simple questionnaire on calf pain while walking, and determination of the serum uric acid level might help in identifying those at high risk of ischemic CVD. Leukocyte activation seems to be an important factor both in atherosclerosis and ischemic CVD, and regarding outcome after ischemic CVD. The plasma levels of leukocyte activation markers might be useful in risk assessment, and possible targets for therapeutic medical intervention.
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| 10. |
- Filipsson, Karin
(författare)
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Regulation of Islet Function by the Neuropeptide PACAP
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is known that parasympathetic, sympathetic and sensory nerves innervate the islets and that these nerves harbor both classical neurotransmitters and neuropeptides. However, the neural influence on islet hormone release is complex and not yet fully understood A recently discovered pancreatic neuropeptide is pituitary adenylate cyclase-activating polypeptide (PACAP). The aim of this thesis was to establish the role of PACAP in the regulation of islet function by using a variety of cell biological techniques in isolated islets and insulin producing clonal cells, in combination with in vivo studies in mice and humans. PACAP was localized to pancreatic nerves within the islets, and two of the three established PACAP receptors were expressed in islet cells. PACAP stimulated insulin secretion from isolated mouse and rat islets, as well as in the insulin producing clonal cell lines HIT-T15 and RINm5F. This action was accompanied by formation of cAMP and increases in cytoplasmic Ca2+ and Na+ and dependent on the extracellular concentrations of glucose, Ca2+ and Na+. Furthermore, addition of specific PACAP antisera to isolated rat islets inhibited glucose-induced insulin secretion. In anesthetized mice, injection of glucose together with PACAP27 increased plasma insulin levels, without affecting plasma glucose levels compared to controls injected with glucose alone. Plasma glucagon and plasma adrenaline levels were increased by injection of PACAP. By analyzing the data according to the minimal model technique, PACAP reduced insulin sensitivity without altering glucose effectiveness. Injection of a specific PACAP receptor antagonist in anesthetized mice prior to presentation of a gastric glucose gavage reduced plasma insulin levels compared to controls given saline. Finally, infusion of PACAP27 in humans increased circulating insulin and glucagon levels, without altering glucose elimination rate. These results shows that PACAP is exclusively a neuropeptide in the islets, that the insulinotropic action of PACAP is mediated by activation of adenylate cyclase in combination with cytoplasmic changes in Ca2+ and Na+, and that PACAP contributes to glucose- and meal-induced insulin secretion. This suggests that PACAP is a neuropeptide in the endocrine pancreas of physiological importance for the regulation of islet function.
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