Systemic lupus erythematosus (SLE) is a systemic inflammatory disease. Clinically, the distinction between ongoing inflammation attributed to SLE, and organ damage due to medication or co-morbidities remains challenging. In addition, SLE is a heterogeneous disease where the various disease phenotypes complicate the search for biomarkers that adequately reflect disease activity and/or signs of increasing organ damage. The aim of the thesis was to investigate and evaluate potential new biomarkers of disease activity and/or organ damage in SLE patients. High mobility group box protein-1 (HMGB1) is a nuclear non-histone protein that can shuttle to the cytoplasm, become secreted extracellularly, and participate in systemic inflammation. Administration of monoclonal anti-HMGB1 antibodies has been reported both to attenuate and intensify disease in animal models of arthritis and lupus. In Paper I of the thesis, circulating anti-HMGB1 was found in 23% of the SLE patients and correlated with disease activity variables. The biological role of these autoantibodies remains to be elucidated. As a consequence of massive circulating levels of cellular debris and immune complexes, SLE patients have insufficient capacity to remove such material via the reticuloendothelial system. Pentraxin 3 (PTX3) may possibly protect against lupus flares due to classical complement activation, opsonization of apoptotic cells, and cytokine induction. In Paper II, circulating PTX3 was found to be inhibited or exhausted by interferon (IFN)-α, a key cytokine of SLE pathogenesis, and serum levels of PTX3 in SLE patients were inversely related to IFN-α levels. Suppressed PTX3 levels may contribute to a vicious circle resulting in impaired waste clearance, autoantigen exposure and autoantibody production, and sustained disease activity. Osteopontin (OPN), a protein known to influence cell signaling and apoptosis, has been proposed as a marker of organ damage in pediatric lupus. In a Swedish cross-sectional study, circulating OPN levels were found to be raised in SLE (Paper III). In patients with recent-onset disease, OPN reflected disease activity, while in established disease, OPN appeared to mirror damage accrual and cardiovascular damage. In Paper IV, OPN was instead analyzed in an international longitudinal multi-center study based on patients with recent-onset SLE and follow-up data. OPN turned out to be a poor predictor of organ damage, but significant associations were observed between OPN and disease activity both at disease onset, as well as over 5 years of follow-up. In conclusion, increased anti-HMGB1 antibody and decreased PTX3 levels could potentially sustain the impaired waste-disposal. Of the molecules analyzed in this thesis, OPN seems to be the best marker of disease activity. Further studies of these proteins may help to better understand SLE pathogenesis and to optimize treatment of patients.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients. In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment. To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery. / Parkinsons sjukdom (PS) är en av de vanligaste s.k. neurodegenerativasjukdomarna och orsakas av förlust av dopamin(DA)producerande nervceller i hjärnan. Detta orsakar motoriska symptom såsom skakningar, stelhet och förlångsammade rörelser. Levodopa (LD) är ett ämne, som kan omvandlas till DA i hjärnan och ge symptomlindring och det är oftast förstahandsval vid behandling av patienter med PS. Flera faktorer påverkar tillgängligheten av LD, bl.a. den hastighet som magsäcken tömmer sig med och denna verkar förlångsammad hos personer med PS vilket ger sämre tillgänglighet av LD i blodet och därmed i hjärnan. LD bryts även ner i hög grad av olika enzym ute i kroppen vilket leder till mindre mängd LD som hamnar i hjärnan och till fler nedbrytningsprodukter som orsakar biverkningar. Tillägg av enzymhämmare leder till ökad mängd LD som kan nå hjärnan och omvandlas till DA. Det anses viktigt att undvika höga toppar av LD i hjärnan då dessa verkar bidra till utvecklandet av besvärliga motoriska komplikationer hos patienter med PS. Om LD ges mer kontinuerligt, exempelvis som en kontinuerlig infusion in i tarmen eller i blodet, så minskar dessa motoriska komplikationer. Inopererande av stimulatorer i vissa delar av hjärnan (DBS) har också visat sig minska dessa motoriska komplikationer och även resultera i att man kan minska LD-dosen. Huvudsyftet med den här avhandlingen är att studera LD hos patienter med PS; i blod och fettvävnad då LD ges i tablettform och se om det finns något samband med LD-upptag och hastigheten på magsäckstömningen (MT) och om kontinuerligt given LD påverkar LD-upptaget eller MT; i blod och i ryggmärgsvätska då enzymhämmarna entakapon och karbidopa tillsätts LD; i hjärna vid behandling med DBS och då LD ges både som tablett och som infusion i blodet. Sammanfattningsvis kan vi se att LD-upptaget är mer gynnsamt hos patienter med PS i tidigare skede av sjukdomens komplikationsfas. MT är förlångsammad hos patienter med PS och det är inget tydligt samband mellan LD-upptag och MT eller mellan MT och sjukdomsgrad. Kontinuerligt given LD minskar LDnivåerna. Enzymhämmaren entakapon ökar den maximala koncentrationen av LD i blod och ryggmärgsvätska och effekten är mer tydlig vid tillägg av karbidopa vilket är viktigt att ta i beaktande vid behandling av PS för att undvika höga toppar av LD i hjärnan. LD ökar i hjärnan då man behandlar med LD i tablettform och som infusion i blodet och DA-nivåerna i hjärnan följer LD väl vilket visar på att patienter med PS fortfarande kan omvandla LD till DA trots trolig uttalad brist av de DA-producerande nervcellerna i hjärnan. DBS verkar öka DA i vissa områden i hjärnan och tillsammans med LD-infusion i blodet verkar det även öka LD i hjärnan och det kan förklara varför man kan sänka LDdosen efter DBS-operation.

Diagnosticering av neuroborrelios baseras på en kombinerad bedömning av neurologiska symtom, serologiska tester för Borrelia-specifika antikroppar och analys av cerebrospinalvätska för att räkna antalet vita blodkroppar och mäta nivåer av kemokinet CXCL13. Nyligen publicerade studier har visat på att analys av IgM-antikroppar riktade mot Borrelia inte är ett lika starkt laboratoriestöd som analys av IgG-antikroppar. Analys av IgM-antikroppar har bidragit till högre antal falskt positiva svar på grund av ospecifik reaktivitet till andra patogener och persisterande antikroppar från tidigare infektioner. Syftet med denna studie var att utvärdera det diagnostiska värdet av att analysera IgM antikroppar i cerebrospinalvätska och serumprover för patienter med misstänkt neuroborrelios. Dessutom jämfördes prestandan mellan två kemiluminiscens immunanalyser, LIAISON (DiaSorin, Italy) och VirClia (Vircell, Spain). För utvärderingen analyserades 80 patientprover på laboratoriet för Klinisk Mikrobiologi på Länssjukhuset Ryhov i Jönköping, Sverige.  För att konfirmera positiva resultatet från de två kemiluminiscens immunanalyserna användes immunoblot, EUROLINE (EUROIMMUN, Germany). Sammanfattningsvis finns det inte tillräckligt med bevis att analys av IgM har ett tillräckligt diagnostiskt värde för att bekräfta en misstänkt neuroborrelios-diagnos. Jämförelsen mellan två kemiluminiscens immunanalyser visade att VirClia kan vara ett lämpligare alternativ än LIAISON när få prover analyseras. / The diagnosis of neuroborreliosis is based on a combined evaluation of neurological symptoms, serological tests for Borrelia-specific antibodies, cerebrospinal fluid analysis to measure white blood cell count and chemokine CXCL13 levels. Recently published data has shown that analysis of IgM antibodies against Borrelia is not as supportive in establishing a clinical diagnosis as IgG antibodies. IgM analysis has contributed to higher false-positive rates because of unspecific reactivities to other biological agents and persistent antibodies from prior infections.  The purpose of this study was to assess the diagnostic value of analysing IgM antibodies in cerebrospinal fluid and serum samples from patients with suspected neuroborreliosis. The performance of two chemiluminescent immunoassays, LIAISON (DiaSorin, Italy) and VirClia (Vircell, Spain), were compared as well. For this assessment, 80 patient samples were analysed at the Laboratory of Clinical Microbiology in Jönköping County, Sweden. Immunoblotting, EUROLINE (EUROIMMUN, Germany), was utilised to validate positive results from the chemiluminescent immunoassays. In conclusion, there is no convincing evidence to suggest that IgM analysis has sufficient diagnostic value to confirm a suspected diagnosis of neuroborreliosis. The comparison of two immunoassays showed that VirClia could be a valid alternative to LIAISON when analysing fewer samples at a time.

Vid elektroencefalografi (EEG) används intermittent ljusstimulering för att detektera eventuell fotoparoxysmal reaktion (PPR) hos patienter, som tecken på en fotosensitivitet och stöd för en misstanke om epilepsi. Intermittent ljusstimulering innebär att patienten exponeras för en stroboskoplampa som ger ljus med frekvenser mellan 1–60 Hz. PPR karaktäriseras av spikes, spike-waves eller polyspike-waves som uppkommer bilateralt och synkront, symmetriskt och generaliserat. Intermittent ljusstimulering är en provokation som utförs vid rutin-EEG som tolkas på Skånes universitetssjukhus mellan 6 månader och 70 års ålder. Studier har dock visat att PPR sällan provoceras fram i äldre åldersgrupper. För äldre åldersgrupper kan det istället vara till större förmån att använda andra former av provokationer. Syftet med studien var att kartlägga förekomsten av PPR i olika åldersgrupper. Åldersfördelningen studerades på patienter med PPR som undersökts med rutin-EEG vilka tolkades på Skånes universitetssjukhus under perioden 2017-2020. Av 4050 rutin-EEG hade 3821 utfört intermittent ljusstimulering. Av dessa hade 1,4 % PPR med ett medelvärde av åldern på 17 år och standardavvikelse på 10 år. PPR var vanligare hos yngre (p<0,001) och 91 % av patienterna med PPR var under 30 år. PPR var även vanligare hos kvinnor (p<0,001) och motsvarade 84 % av undersökningarna med PPR. Konklusionen av studien är att PPR är vanligare hos kvinnor och patienter under 30 år. / Electroencephalography (EEG) uses intermittent photic stimulation to detect possible photoparoxysmal response (PPR) in patients, as a sign of photosensitivity and as a contribution in the diagnosis of a suspected epilepsy. Intermittent photic stimulation means that the patient is exposed to flashing lights from a stroboscope lamp that provides light with frequencies between 1–60 Hz. PPR is characterized by spikes, spike-waves or polyspike-waves that occur bilaterally and synchronously, symmetrically and generalized. Intermittent photic stimulation is a provocation performed during routine-EEG that is interpreted at Skåne university hospital between 6 months and 70 years of age. However, studies have shown that PPR is rarely provoked in older age groups. For older age groups, it may instead be a greater advantage of using other forms of provocative methods. The purpose of this study was to map how common PPR is in different age groups. The age distribution was studied on patients with PPR who were examined with a routine EEG that was interpreted at Skåne university hospital during the period 2017-2020. Of the 4050 routine EEG, 3821 had performed intermittent photic stimulation. Of these 1.4 % had PPR with a mean age value of 17 years and a standard deviation of 10 years. PPR was more common in younger age groups (p<0.001) and 91% of the patients with PPR were younger than 30 years old. PPR was also more common in females (p <0.001), corresponding to 84 % of the examinations with PPR. The conclusion of the study is that PPR is more common in females and in patients younger than 30 years old.

Syfte: Syftet med denna studie var att undersöka sambandet mellan fysisk aktivitetsnivå, depressiva symtom och funktionshinder hos personer med Parkinsons sjukdom. Därtill kartlägga fysisk aktivitetsnivå, depressiva symtom samt funktionshinder bland personer med Parkinsons. Bakgrund: Parkinsons sjukdom är en av de mest förekommande neurodegenerativa sjukdomarna. Sjukdomen är kopplad till både motoriska och icke-motoriska symtom såsom depressiva symtom. Metod: 30 personer inkluderades i denna studie. I denna studie användes IPAQ-SF för att mäta fysisk aktivitetsnivå, MADRS-S för att mäta depressiva symtom samt WHODAS 2.0 för att skatta funktionshinder. Formulären sammanställdes i en webbenkät som publicerades via länk på Facebooksidor ägnade åt Parkinsons sjukdom. Resultat: Utav inkluderade i studien hade 4 (13.3%) låg fysisk aktivitetsnivå, 13 (43.3%) måttlig samt 13 (43.3%) hög. 16 (53.3%) klassades som väsentligen obesvärad, 11 (36.7%) som mild depression, 3 (10.0%) som måttlig samt ingen som svår depression. Bland de inkluderade var medianen för WHODAS 2.0 enligt följande: förstå och kommunicera 3.5 (2.0-5.0), förflyttning 4.5 (2.5-6.5), personlig vård 2.0 (2.0-3.5), relationer 4.0 (3.0-5.5), dagliga aktiviteter 4.5 (3.0-6.5) samt delaktighet i samhället 4.0 (3.0-6.0). Sambandet mellan fysisk aktivitetsnivå och depressiva symtom gav r=0.31 p=0.10. Sambandet mellan fysisk aktivitetsnivå och funktionshinder visade r=0.45 p=0.02. Sambandet mellan depressiva symtom och funktionshinder visade r=0.74 p=0.01. Slutsatser: En måttlig till hög fysisk aktivitetsnivå var vanligt. Likaså var förekomsten av depression omfattande. Förekomsten av funktionshinder var därutöver relativt låg. Korrelationen mellan samtliga variabler anses vara låg frånsett den mellan depressiva symtom och funktionshinder, vilken var måttlig. / Aim: The aim of this study is to explore the correlation between physical activity level, depressive symptoms and health and function in persons with Parkinson’s disease. In addition, this study aims to examine and map physical activity level, depressive symptoms and health and function among persons with Parkinson’s disease. Background: Parkinson’s disease is one the most widespread neurodegenerative diseases. The disease can present itself in either motor or non-motor symptoms, such as depressive symptoms. Method: 30 participants were included in this study. IPAQ-SF was used to measure physical activity level, MADRS-S to measure depressive symptoms and WHODAS 2.0 to measure health and function. The questionnaires were compiled in a web survey which was then posted on various Facebook pages aimed at Parkinson’s disease. Results: Among participants included 4 (13.3%) had low physical activity level, 13 (43.3%) moderate and 13 (43.3%) high. 16 (53.3%) were classed as having no depression, 11 (36.7%) as mild depression, 3 (10.0%) as moderate and none as severe depression. The median for the respective domain of were as follows: cognition 3.5 (2.0-5.0), mobility 4.5 (2.5-6.5), self care 2.0 (2.0-3.5), getting along with people 4.0 (3.0-5.5), life activities 4.5 (3.0-6.5), participation 4.0 (3.0-6.0). The correlation between physical activity level and depressive symptoms provided r=0.31 p=0.10, physical activity level and health and function r=0.45 p= 0.02 and depressive symptoms and health and function r=0.74 p=0.01. Conclusions: This study demonstrated a prominent occurance of high and moderate levels of physical activity. Likewise, the prevalence of depression was extensive. In addition, the incidence of disability was apparently low. The correlation between all variables is considered to be low apart from that between depressive symptoms and disability, which was moderate.

The liver is one of the largest organs within the human body and it handles many vital tasks such as nutrient processing, toxin removal, and synthesis of important proteins. The number of people suffering from chronic liver disease is on the rise, likely due to the present ‘western’ lifestyle. As disease develops in the liver there are pathophysiological manifestations within the liver parenchyma that are both common and important to monitor. These manifestations include inflammation, fatty infiltration (steatosis), excessive scar tissue formation (fibrosis and cirrhosis), and iron loading. Importantly, as the disease progresses there is concurrent loss of liver function. Furthermore, postoperative liver function insufficiency is an important concern when planning surgical treatment of the liver, because it is associated with both morbidity and mortality. Liver function can also be hampered due to drug-induced injuries, an important aspect to consider in drug-development. Currently, an invasive liver needle biopsy is required to determine the aetiology and to stage or grade the pathophysiological manifestations. There are important limitations with the biopsy, which include, risk of serious complications, mortality, morbidity, inter- and intra-observer variability, sampling error, and sampling variability. Cleary, it would be beneficial to be able investigate the pathophysiological manifestations accurately, non-invasively, and on regional level. Current available laboratory liver function blood panels are typically insufficient and often only indicate damage at a late stage. Thus, it would be beneficial to have access to biomarkers that are both sensitive and responds to early changes in liver function in both clinical settings and for the pharmaceutical industry and regulatory agencies. The main aim of this thesis was to develop and evaluate methods that can be used for a ‘non-invasive liver biopsy’ using magnetic resonance (MR). We also aimed to develop sensitive methods for measure liver function based on gadoxetate-enhanced MR imaging (MRI). The presented work is primarily based on a prospective study on c. 100 patients suffering from chronic liver disease of varying aetiologies recruited due to elevated liver enzyme levels, without clear signs of decompensated cirrhosis. Our results show that the commonly used liver fat cut-off for diagnosing steatosis should be lowered from 5% to 3% when using MR proton-density fat fraction (PDFF). We also show that MR elastography (MRE) is superior in staging fibrosis. Finally we presented a framework for quantifying liver function based on gadoxetate-enhanced MRI. The method is based on clinical images and a clinical approved contrast agent (gadoxetate). The framework consists of; state-of the-art image reconstruction and correction methods, a mathematical model, and a precise model parametrization method. The model was developed and validated on healthy subjects. Thereafter the model was found applicable on the chronic liver disease cohort as well as validated using gadoxetate levels in biopsy samples and blood samples. The liver function parameters correlated with clinical markers for liver function and liver fibrosis (used as a surrogate marker for liver function). In summary, it should be possible to perform a non-invasive liver biopsy using: MRI-PDFF for liver fat and iron loading, MRE for liver fibrosis and possibly also inflammation, and measure liver function using the presented framework for analysing gadoxetate-enhanced MRI. With the exception of an MREtransducer no additional hardware is required on the MR scanner. The liver function method is likely to be useful both in a clinical setting and in pharmaceutical trials.

Alzheimer’s disease (AD) is the leading cause of dementia and is alone responsible for 60-70% of all cases of dementia. Though sharing clinical symptoms with other types of dementia, the hallmarks of AD are the abundance of extracellular depositions of β-amyloid (Aβ) plaques, intracellular neurofibrillary tangles of hyper phosphorylated tau proteins and synaptic depletion. The onset of the physiological hallmarks may precede clinical symptoms with a decade or more, and once clinical symptoms occur it may be difficult to separate AD from other types of dementia based on clinical symptoms alone. Since the introduction of radiolabeled Aβ tracer substances for positron emission tomography (PET) imaging it is possible to image the Aβ depositions in-vivo, strengthening the confidence in the diagnosis. Because the accumulation of Aβ may occur years before the first clinical symptoms are shown and even reach a plateau, Aβ PET imaging may not be feasible for disease progress monitoring. However, a negative scan may be used to rule out AD as the underlying cause to the clinical symptoms. It may also be used as a predictor to evaluate the risk of developing AD in patients with mild cognitive impairment (MCI) as well as monitoring potential effects of anti-amyloid drugs.Though currently validated for dichotomous visual assessment only, there is evidence to suggest that quantification of Aβ PET images may reduce inter-reader variability and aid in the monitoring of treatment effects from anti-amyloid drugs.The aim of this thesis was to refine existing methods and develop new ones for processing, quantification and visualization of Aβ PET images to aid in the diagnosis and monitoring of potential treatment of AD in clinical routine. Specifically, the focus for this thesis has been to find a way to fully automatically quantify and visualize a patient’s Aβ PET image in such way that it is presented in a uniform way and show how it relates to what is considered normal. To achieve the aim of the thesis registration algorithms, providing the means to register a patient’s Aβ PET image to a common stereotactic space avoiding the bias of different uptake patterns for Aβ- and Aβ+ images, a suitable region atlas and a 3-dimensional stereotactic surface projections (3D SSP) method, capable of projecting cortical activity onto the surface of a 3D model of the brain without sampling white matter, were developed and evaluated.The material for development and testing comprised 724 individual amyloid PET brain images from six distinct cohorts, ranging from healthy volunteers to definite AD. The new methods could be implemented in a fully automated workflow and were found to be highly accurate, when tested by comparisons to Standards of Truth, such as defining regional uptake from PET images co-registered to magnetic resonance images, post-mortem histopathology and the visual consensus diagnosis of imaging experts.

<p>Neuropeptide Y (NPY) is known to influence a vast number of physiological and behavioral processes such as vasoconstriction, circadian rhythms, feeding, anxiety and memory. Peptides of the NPY family bind to five different cloned G-protein coupled receptor subtypes (Y1, 2, 4-6). The studies compiled in this thesis present inter-species comparisons of sequence similarities, binding properties and expression patterns among receptors of the NPY family.</p><p>Cloning of Y1 and Y2 receptor subtypes from guinea pigs revealed strong binding profile similarity to the corresponding human receptors. Previously demonstrated atypical binding profiles in the caval vein of guinea pigs were concluded to result from other receptors than the cloned Y1 and Y2 receptors, or possibly combinations of distinct receptor subtypes.</p><p>The guinea pig Y5 receptor was found to be expressed in regions of the brain that have been indicated as important for regulation of food intake. Expression in the hypothalamus, amygdala and brain stem was noticed, similar to studies in rats and humans. In other brain regions, such as the striatum and hippocampus, some species differences were observed.</p><p>Mutagenesis studies of the human Y1 receptor indicated sites important for binding both of endogenous agonists and synthetic antagonists. Putative new sites of interaction with the Y1 antagonists BIBP3226 and/or SR120819A were recognized. The data were used to construct a three-dimensional structure model, based on a high-resolution bovine rhodopsin model.</p><p>Cloning of the chicken (<i>Gallus gallus</i>) Y1, Y2 and Y5 receptors revealed high sequence similarities with mammalian receptors. Most endogenous ligands bound with similar affinities as to mammalian receptors. The strongest exception was the discovery of high-affinity binding to chicken Y2 of [Leu³¹, Pro³⁴]NPY, which was previously considered to bind non-Y2 receptors only. </p><p>The new human Y1 receptor model provides a basis for further investigations of ligand-receptor interactions which will be aided by information on NPY receptors from other taxa. Guinea pigs are concluded to be a good complement to rats and mice for studying NPY signaling. These results demonstrate the benefits of species comparisons for pharmacological studies.</p>

<p>Grade 2 gliomas are malignant brain tumours affecting otherwise healthy adults. Although the long-term prognosis is poor, many patients are well and may have a high quality of life for several years. There is, however, a large variability in the natural course of the disease which makes it essential to identify patients who might benefit from early surgery or radio-therapy. The aim of the present thesis was to define new and clinically useful prognostic markers that may assist in the initial treatment decision and in patient follow-up.</p><p>A retrospective study of 189 patients with gliomas WHO grade 2 showed no advantage in survival of early tumour resection or radiotherapy, and confirmed that histological subtype and patient age are the most important predictors of survival (I). In 89 patients, the pre-treatment uptake of 11C-methionine (MET) measured with positron emission tomography (PET) was identified as a prognostic marker for survival (II). At the time of tumour progression, irradiated tumours demonstrated signs of a residual radiotherapeutic effect that correlated with the pre-treatment uptake of MET (III). Pre-treatment uptake of MET may, therefore, be important both in predicting the natural course of the disease and the response after treatment. Immunohistochemical staining of 40 tumour samples showed an inverse association between the number of tumour cells expressing platelet-derived growth factor alpha receptor (PDGFRa) and survival (IV). Also, a reduction was observed in the number of receptor-positive cells after malignant transformation, supporting the prognostic value of PDGFRa.</p><p>Lumbar puncture was performed in eight patients with newly diagnosed low-grade gliomas to identify three important growth factors in tumour development. Neither PDGF nor vascular endothelial growth factor (VEGF) were detected in the cerebrospinal fluid (CSF), and fibroblast growth factor 2 (FGF-2) was measurable at extremely low concentrations in two of the patients (V). A proteome screening of the CSF, using two-dimensional gel electrophoresis and mass spectrometry, detected alpha 2-HS glycoprotein at significantly higher concentrations than in a control group (VI). This glycoprotein emerges as a novel substance in glioma research and may be of great interest because of its suggested involvement in the embryonic development of the neocortex.</p>

<p>The purpose of this investigation was to study sexual function in women with neurological disorders at fairly distinct and separate locations. The dissertation comprises descriptive, retrospective, quantitative studies on sexual functioning in women with hypothalamo-pituitary disorders (HPD) (<i>n</i>:48), multiple sclerosis (MS)(<i>n</i>:47), and insulin-dependent diabetes mellitus (IDDM) (<i>n</i>:42). The results werecompared with those in an age-matched control group (C) (<i>n</i>:42), and as reported by representative Swedish women (<i>n</i>:742) in the Swedish sex survey SiS). The studies were based on comprehensive interviews, neurological examinations, incl. Vibration Perception Thresholds (IDDM), concentrations of prolactin and testosterone in serum (HPD), and a checklist on life satisfaction (IDDM, C, and SiS).</p><p>Sexual dysfunction was prevalent in almost all women with HPD and MS, and in 40% of the IDDM group. The problem of insufficient vaginal lubrication was more common in those with neurological disorders than among women in the SiS group. Sexual problems caused by reduced libido and orgasmic difficulties were more commonin the HPD and MS groups than in the SiS group. In the HPD group, women with intrasellar adenomas had better sexual function than women having expansively growing pituitary adenomas with both intra- and suprasellar extension. Normal serum testosterone values correlated to masturbation activity. Amenorrhea and older age werecorrelated with sexual problems in all groups. In the MS group, symptoms of a weak pelvic floor and of bladder and bowel dysfunction were correlated with reduced lubrication and orgasmic ability. In the IDDM group, signs of autonomic neuropathy were correlated with sexual dysfunction. Concerning life satisfaction generally,proportionately fewer women with IDDM were satisfied or very satisfied, though differing significantly from the other two groups in only two domains of life: contacts with friends, and physical health.</p>