Impulses coming from peripheries are modified in the spinal cord and transmitted to the brain. Several neurotransmitters have been involved in the processing of impulses in the spinal dorsal horn. Acetylcholine (ACh) is one of many neurotransmitters involved in the regulation of nociception in the spinal cord. In this study we investigated the role of nicotinic, muscarinic, serotonergic and GABA receptors in the regulation of spinal ACh release since these receptors are reported to be involved in spinal nociceptive processes. Different receptor ligands were infused intraspinally via microdialysis and the spinal ACh release was measured by on-line HPLC. Receptor-ligand binding studies were performed with spinal cord homogenates as well as receptors expressed in cells. In the first study, we found that nicotine and some of the nicotinic antagonists used increased ACh release suggesting that spinal ACh release is regulated by different nAChRs. Nicotine and nicotinic agonists may act on different types of receptors with different affinity to produce the observed net effect of increased ACh release. We propose the possibility of an involvement of three different nicotinic receptor subtypes in the regulation of spinal ACh release. The effect of epibatidine, which is regarded as a nicotinic agonist, on muscarinic receptors was investigated in the second study. We propose that epibatidine, in μM concentrations, is a partial muscarinic receptor agonist that may interact with spinal muscarinic receptors to increase ACh release. The dual action on both nAChRs and mAChRs may explain the potent analgesic effect observed after intra-spinal epibatidine administration. In the third study, we investigated the role of serotonin receptor involvement in ACh release control. The results suggest that only 5-HT1A and 5-HT2A receptors are involved in spinal ACh release. Considering current knowledge, the most probable location of 5-HT2A receptors is on cholinergic neurones. On activation of the 5-HT2A receptors the cellular excitability of cholinergic neurones is increased which results in an increasing ACh release. The 5-HT1A receptors might be located on cell bodies of GABA neurones which inhibit the firing rate of the GABA neurones when activated by serotonin. In the fourth study, we investigated the GABA receptor involvement in the regulation in spinal ACh release. We found that GABAA receptors are tonically inhibiting spinal ACh release. The results further suggest that GABAB receptors also are involved in the regulation of spinal ACh release. However, unlike GABAA antagonists, GABAB antagonists do not increase ACh release. This suggests that GABAB receptors are not tonically regulating the spinal ACh release.

Kritiskt sjuka patienter riskerar att utveckla malnutrition och ska erhålla nutritionsstöd i form av enteral nutrition (EN) och parenteral nutrition (PN). Trots att flödesscheman för EN används på många intensivvårdsavdelningar får patienter sällan 100 % av ordinerat kaloribehov. Syftet med denna studie var att utvärdera införandet av flödesschema för enteral nutrition på en neurokirurgisk intensivvårdsavdelning (NIVA). Som metod valdes en retrospektiv, kvantitativ studie. En granskning av journaldata från förgruppen (n =28), fem månader innan införandet av flödesschemat och data ifrån eftergruppen (n =20), fem månader efter införandet av flödesschemat har gjorts. En journalgranskningsmall användes vid insamlandet av data. Det som granskades är starttid av EN, antalet kalorier administrerat via EN, PN och EN+PN. Vidare granskades mängd ventrikelaspirat, frekvens av avföring och observerade avbrott av EN. Införandet av flödesschema för EN visade att eftergruppen administrerades totalt mera kalorier än om inte flödesschema användes. Eftergruppen administrerades signifikant mera kalorier via EN+PN och via PN enskilt. Skillnaden mellan ordinerade kalorier och administrerade kalorier var mindre i eftergruppen. EN startades några timmar senare i eftergruppen och förgruppen administrerades mera kalorier via EN. Eftergruppen redovisar signifikant mindre mängd ventrikelaspirat, och kräkning bredvid sond var mindre frekvent i eftergruppen. Fortsatt forskning behövs med RCT-studier som evidensbaserar flödesschema för EN.

The prevalence of spasticity after first-ever stroke is approximately 20%, but there are no data on the prevalence of disabling spasticity.The reported prevalence of pain after stroke varies between 19% and 74%, whether pain is associated with spasticity is not known. Until now, there is no health economic analysis of patients with spasticity after stroke. Methods: Two groups of patients were studied. Cohort I was a cross-sectional survey. A representative sample of 140 patients was investigated 1 year after their first-ever stroke. Spasticity was defined as ≥ 1 score on the modified Ashworth scale, disabling spasticity was defined as spasticity having such an impact that intervention, e.g. intensive physiotherapy, orthoses or pharmacological treatment, should be offered. Pain was assesed with the Visual Analogue Scale. All direct costs during one year were identified and converted into Purchasing Power Parities US dollar (PPP$). Cohort II was a prospective cohort study. Forty-nine patients were examined at day 2–10, at one month, and at six months after their first-ever stroke. Assessment and definitions were similar as for cohort I. Results: Spasticity occurs within 1 month and disabling spasticity occur within 6 months. After one year, the prevalence of spasticity was 17% and that of  disabling spasticity 4%. Disabling spasticity was more frequent in the upper extremity. There was an independent effect of severe upper extremity paresis (OR 22, CI 3.9–125) and age below 65 years (OR 9.5, CI 1.5–60). The prevalence of stroke-related pain was 21% after one year. Stroke-related pain was associated with paresis (OR 3.1, 95% CI 1.2–7.7), sensory disturbance (OR 3.1, 95% CI 1.1–8.9) and depression (OR 4.1, 95% CI 1.4–13), but not with spasticity as an independent variable. The majority of the direct costs for one year (78%) were associated with hospitalization, whereas 20% was associated with municipality services. Only 1% of all direct costs were related to primary health care and 1% to medication. The mean (median, inter-quartile range) direct cost for stroke patients with spasticity was PPP$ 84 195 (72 116, 53 707) compared to PPP$ 21 842 (12 385, 17 484) for stroke patients without spasticity (P < 0.001).

Syftet med denna uppsats är att beskriva hur skillnaderna i det pedagogiska och det medicinska perspektivet konstrueras i kurslitteraturen för blivande lärare och läkare, samt hur barn med uppmärksamhetsstörningar konstrueras i litteraturen. Metoden i denna studie baseras på textanalys. Resultatet visar att olika diskurser speglas i kurslitteraturen för respektive utbildning och att barn med uppmärksamhetsstörningar därmed beskrivs på skilda sätt. Kurslitteraturen för läkarstudenter presenterar avvikelse utifrån det som anses normalt och avvikelse som begrepp har där en central roll. Kurslitteraturen för lärarstudenter presenterar olikheter som en utmaning vilka bör ligga till grund för positiv utveckling hos eleven.  Slutsatsen är att barn med neuropsykiatriska störningar/barn i behov av särskilt stöd beskrivs utifrån olika diskurser och att kurslitteraturen för respektive utbildning förespråkar olika behandlingar för dessa barn. Läkaren nämns nästan enbart i den pedagogiska litteraturen i samband med en diagnos, eller i de samband där specialpedagogens utveckling genom samverkan med olika professioner nämns. Den medicinska litteraturen beskriver sällan lärarens roll utan detta sker enbart i ett fåtal fall, däremot benämns skolmiljön som ett område där avvikande beteende kan definieras. / The purpose of this essay is to describe how differences in the educational and medical perspective are constructed in the literature for future teachers and doctors, and also how children with attention disorders are constructed in this literature. A text analysis was based on books from medical training program and teacher training program. The results show that different discourses are reflected in the literature and that children with attention disorders hence are described in different ways. The course literature for medical students present deviation from what is considered normal, and deviation as a concept has a central role consistently through the literature. The course literature for teacher students presents differences as a challenge which should be the basis for positive development of the student. The conclusion is that children with neuropsychiatric disorders/ children with special needs are described by various discourses and that the course literature for medical students and teacher students advocate different treatments for these children. The medical doctor is almost only referred in the educational literature when associated with a diagnosis. The medical literature rarely describes the role of the teacher, this happens only in a few cases, however the school environment is more frequently mentioned as an area in which deviant behavior can be defined.

The focus of this thesis is the life and death of adult retinal ganglion cells (RGCs). RGCs are neurons that convey visual information from the retina to higher centers in the brain. If the optic nerve is transected (ONT), adult RGCs die by a form of cell death called apoptosis, and a general hypothesis is that neurotrophic factors can support the survival of injured neurons. With the intention to gain knowledge about systems that can be used to decrease RGC death after ONT, we have studied growth factor receptors belonging to the tyrosine kinase family of receptors (RTK), known to mediate important cell survival signals. We found that the RTK Ret and its coreceptor GFRα1 were expressed by RGCs, and to test the above-mentioned hypothesis, we intraocularly administered glial cell-line derived factor, which activates a Ret-GFRα1 complex, and found transiently mediated RGC survival after ONT. To identify new, potential neurotrophic factor receptors expressed by RGCs, with the aim to improve RGC survival after ONT, we developed a method for the molecular analysis of acutely isolated RGCs. The method involves retrograde neuronal tracing, mechanical retinal layer-separation, and isolation of individual RGCs under UV-light for RT-PCR analysis. Using this method, in combination with degenerate PCR directed towards the tyrosine kinase domain, several RTKs were identified. Axl, Sky, VEGFR-2, VEGFR-3, CSF-1R, and PDGF-βR are expressed by adult RGCs, and considered to be receptors with potential neurotrophic activity. Other results have shown that RGCs may require depolarization or increase in intracellular cAMP levels in order to fully respond to exogenously added trophic factors. We found that melanocortin receptors (MCRs) were expressed by RGCs, and MCRs can mediate elevation of intracellular AMP. We observed that α-MSH induced neurite outgrowth from embryonic retinal cells, indicating that MCR ligands have direct effects on retinal cells. RTKs and their ligands may be involved in endogenous systems for neuronal repair within the visual system. BDNF, NT-3, FGF2, and HGFR all increased in the retina after ONT and may be a part of an activated system for neuronal repair locally within the retina. Adult axotomized RGCs die by apoptosis, therefore we examined the regulation of apoptotic genes after ONT. Bim and Bax increased in the retina after ONT, and may promote death of axotomized RGCs, whereas the increase in Bcl-2 may contribute to limit RGC apoptosis after ONT. All in all, this thesis provides insights into the expression and regulation of molecules involved in the death and survival of RGCs. The results have revealed a number of potential neurotrophic receptors expressed by RGCs, and both identified RTKs and MCRs will serve as new targets in therapeutic approaches aiming at counteraction of RGC death after injury.

Bakgrund: Många av patienterna på en neurointensivvårdsavdelning (NIVA) vårdas med respirator under en längre eller kortare period av vårdtiden. Neurointensivvårdspatienterna bedöms ibland utifrån de kriterier för urträning och extubering som används på allmänna intensivvårdspatienter. Detta kan leda till för tidig extubation med reintubation som följd. Syfte: Redogöra för vilka kriterier som ska bedömas hos neurointensivvårdspatienter inför en extubering. Metod: Litteraturstudie. Resultat och slutsats: Neurointensivvårdspatienter behöver uppfylla en kombination av kriterier inför extubation. Hänsyn ska tas till de generella extubationskriterierna avseende andning och cirkulation. Dessutom ska patienten ha en tillräckligt hög medvetandegrad för att kunna följa någon form av uppmaning. Till sist ska patientens förmåga att hålla fri luftväg bedömas genom observation av hostkraft, sekretmängd/konsistens och svalgfunktion. Det behövs ytterligare forskning för att utröna i hur hög grad neurointensivvårdspatienterna behöver vara medvetna inför extubering och på vilket sätt detta bäst bedöms. Forskning behövs kring ett enhetligt tillvägagångssätt för bedömning av hostkraft, sekretmängd/konsistens och svalgfunktion. / Background: Many of the patients cared for in a neurocritical unit are treated with mechanical ventilation for a longer or shorter period of time during their stay in the unit. When weaning or extubating neurocritical patients, they are sometimes assessed according to the criteria for weaning and extubation used in general intensive care patients. This can cause premature extubation, resulting in re-intubation. Aim: Describe the criteria to be assessed in neurocritical patients prior to extubation. Method: Literature review. Results and conclusion: Neurocritical patients need to fulfil a combination of criteria prior to extubation. The general criteria in terms of respiration and circulation must be taken in to consideration, as well as the patient’s level of consciousness. The patient has to be conscious enough to be able to take directions. Lastly the patient’s ability to protect the airway must be assessed by observation of cough strength, the quantities and viscosity of the secretions and the patient’s swallowing function. Further research is required to ascertain the level of consciousness required in the neurocritical patients prior to extubation and in which way the assessment is best carried out. There is also need for further research considering a standardized measurement for assessing cough strength, the quantities and viscosity of secretions and swallowing function in these patients.

Fatigue är ett vanligt förekommande symtom vid multipel skleros (MS). Denna ihållande och svåra trötthet beskrivs ofta som det svåraste MS-relaterade symtomet att hantera. Symtomet har en negativ påverkan på individens funktionella status samt på livskvaliteten. Syftet med litteraturstudien var att belysa upplevelserna av MS-relaterad fatigue samt hur symtomet påverkar det dagliga livet. Som metod användes en systematisk genomgång av tidigare forskning med en induktiv ansats. Forskning visar att fatigue upplevs som en oavbruten förlamande effekt som uppfattas skilja sig mycket från tidigare upplevd trötthet. Fatigue påverkar hela kroppen och leder till att kroppen blir svårare att styra och hantera. Den begränsade förmågan att utföra önskade aktiviteter påverkar individernas liv negativt. Individer med MS blir tvungna att reglera och planera sitt dagliga liv för att undvika och minska graden av fatigue. En bibehållen självkänsla samt en positiv attityd och en acceptans för sjukdomen och symtomet upplevs minska graden av fatigue. Kommande forskning bör fokusera på individanpassade metoder eller strategier som upplevs minska graden av fatigue.

Pharmacotherapy for Parkinson’s disease (PD) is based on levodopa, the most effective dopaminergic drug. The development of motor complications constitutes the major challenge for new or refined therapies. To evaluate the impact of levodopa pharmacokinetics on motor function, an observational study in the patients’ home environment was carried out. A high variability in plasma levodopa levels was found in all patients, irrespective of treatment regimen. The impact of levodopa pharmacokinetics was further studied in a crossover trial comparing sustained-release tablets and continuous daytime intestinal infusion. Infusion produced significantly decreased variability in plasma levels of levodopa, resulting in significantly normalised motor function. A permanent system for long-term levodopa infusion has been developed and 28 patients have been followed for 87 patient-years. Motor response was generally preserved during the long-term observation period, implying that there is no development of tolerance to infusion therapy. Levodopa tablets are normally used in multiples of 50 or 100 mg, thus a rough estimate of individual dosage. A new concept for individualising levodopa/carbidopa doses with microtablets of 5/1.25 mg is under development. An electronic drug-dispensing device for administering the microtablets was tested on patients with PD. All were able to handle the dispenser and most were interested in future use of the concept. Self-assessment of symptoms is accurate in PD, but traditional paper diaries are associated with low compliance. A wireless electronic diary was compared with a corresponding paper diary. The time-stamped and thus completely reliable patient compliance was 88% with the electronic diary. To conclude, pharmacokinetics of levodopa is the major determinant for motor fluctuations in PD. Every effort to individualise dosage and to smooth out the fluctuations in levodopa concentrations should be made, e.g. by means of microtablets or enteral infusion. Electronic patient diaries for real-time data capture are suitable for PD studies.

Introduktion: Multipel Skleros [MS] är en autoimmun nervsjukdom som påverkar kroppens alla funktioner, genom att nervernas ytskikt, myelin, skadas och bryts ner. Orsaken är okänd och sjukdomen anses vara kronisk, då det i nuläget inte finns något botemedel. Sjukdomen upplevs olika av alla och genom att belysa erfarenheter hos personer med MS, kan sjuksköterskan få en större förståelse för personers situationer och på så vis kunna anpassa vården efter olika behov. Syfte: Litteraturstudiens syfte var att belysa personers erfarenheter av Multipel Skleros. Metod: Litteraturstudien grundades på Polit och Becks (2017) niostegs flödesschema. Sökningar genomfördes i databaserna Cinahl och PubMed. Urval i tre steg och databearbetning genomfördes, vilket resulterade i 15 kvalitativa artiklar. Resultat: Fyra huvudkategorier identifierades: MS – en känslofylld resa, Stöd & relationer, Planera för att vara aktiv och Att bilda familj – från ett kvinnligt perspektiv. Slutsats: Personer med MS upplevde att vägen fram till diagnos var lång och fylld av många olika känslor. Personer med MS ansåg att sjukdomen innebar en ständig kamp att anpassa sig till det vardagliga livet, där stöd och sociala relationer var en stor och viktig del.

Typically developing humans innately place subjective value on social information and orient attention to it. This can be shown through eye tracking and pupillometry, a method used to show attentional engagement. Social brain development and social preference is present from infancy, and is thought to rely on a carefully balanced network of neurotransmitters and neural connections. Autism Spectrum Disorder (ASD) presents altered neural systems which cause individuals to perceive and process social information differently, but the neurophysiology of this difference remains unclear. Previous research shows atypical gaze patterns, hyperarousal, and lack of orienting to social stimuli in ASD. Since autism is highly comorbid and shares traits with other neurodevelopmental disorders, it is difficult to distinguish aspects of these social processing differences. This study used a group of 35 neuropsychiatric patients to investigate how individuals with autism process social and non-social scenes. Eye tracking and pupillometry measures were collected while participants observed images of natural scenes with or without a person. Participants with autism did not show a pupillary response to social images and were slower to fixate on the face  region than the other participants. Additionally there were correlations between clinical measures of social functioning and the length of time it took to fixate to faces. The results highlight important distinctions of social processing in autism. This thesis proposes a new perspective of looking at the social deficits present in autism spectrum disorder. It suggests reframing the current discussion from two leading hypotheses to a unified approach and formally considering the limitations of differing types of stimuli.