Posttraumatic Stress Disorder (PTSD) is a psychiatric condition that can develop following exposure to a traumatic event involving actual or threatened death or serious injury. Responses include intense fear, helplessness or horror. Symptoms are characterised into clusters, described as re-experiencing, avoidance, and arousal. These symptoms, which are also evident in other conditions, have been associated with dysfunctions in the central acetylcholinergic system. Benefits from administering acetylcholinesterase inhibitors (AChEI) to people suffering these symptoms have been demonstrated. Donepezil hydrochloride, a reversible inhibitor of the enzyme acetylcholinesterase, is used in the treatment of conditions with difficulties in cognitive function, but has not been used in PTSD. The aim of this thesis was to determine (1) whether there was a difference in the ACh system in people with PTSD and (2) whether administration of an AChEI would change the symtomatology. IDEX (I¹ ² ³ iododexetimide) has been useful in imaging muscarinic-ACh receptors using Single Photon Emission Computerised Tomography (SPECT) and was utilised to investigate whether cholinergic activity in PTSD is altered. One hundred and sixty eight potential subjects were screened and eleven PTSD subjects were enrolled in the IDEX SPECT study. Three healthy non-PTSD control subjects also completed the study. Due to technical complications only the data obtained from eight PTSD and two control subjects was available for analysis. Imaging data for 2 further healthy non-PTSD control subjects were obtained from another study. Sixteen subjects were enrolled in the donepezil open label study (assessed at baseline, Week 2, 6 and 10). Nine PTSD subjects completed the 10-week trial and seven withdrew prematurely (at or after Week 2) due to side effects or a worsening of PTSD symptoms. For the IDEX SPECT study, a voxel-by-voxel statistical analysis of the PTSD subject group versus the control group showed both areas of reduced and increased IDEX uptake. Significant clusters in the PTSD group with a reduced IDEX uptake centred around the bilateral hippocampus, left insula and right precuneus, while increased IDEX uptake appeared in the caudate head. For the donepezil study, in the per-protocol analysis (including only the 9 subjects that completed the protocol), all psychological assessments revealed a difference between the totals obtained at the Week 10 visit compared to those at the Baseline visit and the improvement was in the order of 51%. The intention-to-treat analysis (including all 16 subjects), a repeated measures Analysis of Variance (ANOVA) with a mixed models approach showed that all psychological measures demonstrated statistically significant benefits of the treatment. All subjects who completed the protocol recounted considerable improvement in their overall PTSD symptom profile, which covered symptoms in each of the three clusters. The results of the IDEX SPECT study suggest that alterations in ACh binding in PTSD are evident and may begin to explain a part of the altered cognitive symptomatology apparent in this condition. The pilot open label donepezil trial provided some preliminary evidence that treatment with an AChEI can lessen the intrusions and distress associated with traumatic memories in people with PTSD. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1374974 / Thesis (M.Med.Sc.) -- University of Adelaide, School of Medicine, 2009

Habil.-Schr. Technische Hochschule Aachen, 1997.

Orientador: Sylvia Maria Ciasca / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T14:33:13Z (GMT). No. of bitstreams: 1 Guimaraes_InesElcione_D.pdf: 4272361 bytes, checksum: 61a706cfbc3b1f7cff0820fbeb662e9a (MD5) Previous issue date: 2008 / Resumo: A doença cerebrovascular (DCV) na infância é considerada rara e interfere drasticamente na evolução da criança. Este estudo teve como objetivo relacionar as achados neuropsicológicos em crianças com DCV isquêmica ou hemorrágica, com variáveis que interferem na doença como: recorrência, etiologia, idade de instalação do quadro. Participaram do estudo 32 crianças com história de acidente vascular cerebral (AVC) isquêmico ou hemorrágico, de ambos os sexos na faixa etária de 6 a 16 anos, que foram submetidos à avaliação neuropsicológica, intelectual, viso-motor, desempenho escolar, exame de imagem funcional, entre outros. A amostra foi selecionada a partir do banco de dados do Grupo de Estudos em DCV na Infância e Adolescência do HC da UNICAMP. Participaram ainda outras 25 crianças que compuseram o grupo controle. O grupo isquêmico com 68,75% da amostra e o hemorrágico com 31,25%, não se diferiram quanto ao sexo, recorrência, crise convulsiva e idade de instalação do AVC. Constatou que 87% evoluíram com seqüela motora e 34,3% com rebaixamento intelectual. O desempenho intelectual foi mais prejudicado frente às seguintes situações: anemia falciforme, idade precoce de instalação do quadro, recorrência, evolução com crise convulsiva, dois hemisférios acometidos, lesão cortico-subcortical e seqüela motora. Verificou-se que 18,7% das crianças do grupo experimental não conseguiram responder à bateria de instrumentos, sugerindo que a lesão em regiões corticais e subcorticais em idade precoce produziram severos prejuízos cognitivos. Palavras chaves: doença cerebrovascular ¿ quociente intelectual - infância ¿ exame de imagem funcional, recorrência / Abstract: The cerebrovascular disease (CVD) during the childhood is rare and interferes drastically in the development of child. The aim of this study is to relate the neuropsychological findings in children with ischemic or hemorrhagic CVD, to variables that interfere in the disease, for example: recurrence, etiology, the age of the installation. Thirty-two children with prior history of ischemic or hemorrhagic stroke, of both sexes in the age group from 6 to 16 years, were subdued to an neuropsychological, intellectual, visual-motor, school performance, cerebral blood flow evaluation; among others, the sample was selected from the Group of Studies in CVD in childhood and adolescence database of the HC of UNICAMP. Twenty-five children also the hemorrhagic with 31,25%, there was no difference in relation of sex, recurrence, seizures and the age of installation of the CVA. It was noticed that 87% grew with motor sequelae and 34,3% with an intellectual reduction. The intellectual performance was more damaged facing these situations: sickle cell disease, premature age of the installation, recurrence, evolution of convulsive crisis, two hemispheres attacked, cortical-subcortical lesion and motor sequelae. It was checked, 18,7% of the children in the experimental group couldn¿t respond to the battery of instruments, suggesting that the lesion in the cortical an subcortical areas in early age produced severe cognitive damages. Key-words: disease cerebrovascular ¿ intelligence quotient ¿ childhood ¿ SPECT ¿ recurrence / Doutorado / Ciencias Biomedicas / Doutor em Ciências Médicas

Nukleärmedicinska bilder som exempelvis SPECT (Single Photon Emission Tomogra-phy) är en bildgenererande teknik som ofta används i många applikationer vid mätning av fysiologiska egenskaper i den mänskliga kroppen. En vanlig sorts undersökning som använder sig av SPECT är myokardiell perfusion (blodflöde i hjärtvävnaden), som ofta används för att undersöka t.ex. en möjlig hjärtinfarkt. För att göra det möjligt för läkare att ställa en kvalitativ diagnos baserad på dessa bilder, måste bilderna först segmenteras och roteras av en biomedicinsk analytiker. Detta utförs på grund av att hjärtat hos olika patienter, eller hos patienter vid olika examinationstillfällen, inte är lokaliserat och roterat på samma sätt, vilket är ett väsentligt antagande av läkaren vid granskning av bilderna. Eftersom olika biomedicinska analytiker med olika mängd erfarenhet och expertis roterar bilderna olika uppkommer variation av de slutgiltiga bilder, vilket ofta kan vara ett problem vid diagnostisering. En annan sorts nukleärmedicinsk undersökning är vid kvantifiering av dopaminreceptorer i de basala ganglierna i hjärnan. Detta utförs ofta på patienter som visar symptom av Parkinsons sjukdom, eller liknande sjukdomar. För att kunna bestämma graden av sjukdomen används ofta ett utförande för att räkna ut olika kvoter mellan områden runt dopaminreceptorerna. Detta är ett tröttsamt arbete för personen som utför kvantifieringen och trots att de insamlade bilderna är tredimensionella, utförs kvantifieringen allt för ofta endast på en eller flera skivor av bildvolymen. I likhet med myokardiell perfusionsundersökningar är variation mellan kvantifiering utförd av olika personer en möjlig felkälla. I den här rapporten presenteras en ny metod för att automatiskt segmentera hjärtats vänstra kammare i SPECT-bilder. Segmenteringen är baserad på en intensitetsinvariant lokal-fasbaserad lösning, vilket eliminerar svårigheterna med den i myokardiella perfusionsbilder ofta varierande intensiteten. Dessutom används metoden för att uppskatta vinkeln hos hjärtats vänstra kammare. Efter att metoden sedan smått justerats används den som ett förslag på ett nytt sätt att automatiskt kvantifiera dopaminreceptorer i de basala ganglierna, vid användning av den radioaktiva lösningen DaTSCAN. / Nuclear medical imaging such as SPECT (Single Photon Emission Tomography) is an imaging modality which is readily used in many applications for measuring physiological properties of the human body. One very common type of examination using SPECT is when measuring myocardial perfusion (blood flow in the heart tissue), which is often used to examine e.g. a possible myocardial infarction (heart attack). In order for doctors to give a qualitative diagnose based on these images, the images must first be segmented and rotated by a medical technologist. This is performed due to the fact that the heart of different patients, or for patients at different times of examination, is not situated and rotated equally, which is an essential assumption for the doctor when examining the images. Consequently, as different technologists with different amount of experience and expertise will rotate images differently, variability between operators arises and can often become a problem in the process of diagnosing. Another type of nuclear medical examination is when quantifying dopamine transporters in the basal ganglia in the brain. This is commonly done for patients showing symptoms of Parkinson’s disease or similar diseases. In order to specify the severity of the disease, a scheme for calculating different fractions between parts of the dopamine transporter area is often used. This is tedious work for the person performing the quantification, and despite the acquired three dimensional images, quantification is too often performed on one or more slices of the image volume. In resemblance with myocardial perfusion examinations, variability between different operators can also here present a possible source of errors. In this thesis, a novel method for automatically segmenting the left ventricle of the heart in SPECT-images is presented. The segmentation is based on an intensity-invariant local-phase based approach, thus removing the difficulty of the commonly varying intensity in myocardial perfusion images. Additionally, the method is used to estimate the angle of the left ventricle of the heart. Furthermore, the method is slightly adjusted, and a new approach on automatically quantifying dopamine transporters in the basal ganglia using the DaTSCAN radiotracer is proposed.

Ejektionsfraktion (EF) är ett mått på den globala systoliska vänsterkammarens funktion. EF är en viktig parameter för den systoliska vänsterkammare funktionen eftersom de terapeutiska samt prognostiska fattade besluten bygger på bland annat detta mått, vilket normalt är ≥ 55 % av slutdiastolisk volym. Vid beräkning av EF används bland annat tvådimensionell (2D) ekokardiografi (2D-EKO) samt myokardscintigrafi i vila (GSPECT). Utifrån 2D-EKO erhålls EF med Biplan Simpson metoden tillämpad i fyrkammarvy och tvåkammarvy i slutdiastole och slutsystole. Med GSPECT i vila erhålls EF värden utifrån QPS och QGS bilderna efter att en automatisk utlinjering av endokardiets konturer genomförts med hjälp av Hermes Medical solution. Syftet med studien var att se om det föreligger en signifikant skillnad för uppmätt EF mellan Myokardscintigrafi (GSPECT) och 2D Ekokardiografi i vila. Studien innefattade 30 deltagare. Deltagarnas uppgifter avidentifierades och inhämtades från tidigare genomförd 2D-EKO respektive GSPECT i vila, med högst 6 månaders mellanrum av legitimerade Biomedicinsk Analytiker. Resultatet av studien förevisade ett p – värde (p=0,000) <0,1% samt r-värde (r = 0,65.) Vilket indikerar på en stark och signifikant korrelation däremot förekommer det en bristande uppnåelse av överstämmelse mellan metoderna utifrån spridningsdiagrammet som ger ( r^2= 0,42). Bland Altmandiagammet noterar att ett gott samband mellan metoderna föreligger och även så gör standardavvikelse för 2D-EKO samt GSPECT som påvisade (50.1±¬¬10,8) respektive (49,1± 15,1). Studien förevisade goda övergripande korrelationer mellan EF härstammande från 2D-EKO och GSPECT. Sammantaget visade studien att metoderna överensstämmer med varandra vid mätning av EF. / Ejection fraction (EF) is a measure of the global systolic left chamber function. EF is a significant parameter for the systolic left ventricle function since therapeutic and prognostic conclusions are based on the left chamber ejection fraction. EF is normally ≥ 55% of the end-diastolic volume. Left ventricle ejection fraction can be determined non-invasively by 2D echocardiography (2D – ECHO) and gated single photon emission computed tomography. Based on 2D echocardiography (2D-ECHO), EF was obtained using the biplane Simpson method applied in four-chamber view and two- chamber views in both end diastole and end systole. With myocardial perfusion (GSPECT), EF values were obtained based on the QPS- and QGS- images after an automatic orientation of endocarditis contours were carried out by Hermes Medical solution. The purpose of this report was to see if there is a significant difference in (EF) between (GSPECT) and (2D-ECHO) at rest. The study included 30 participants. EF values were attained by licensed biomedical scientist. Participants' data were de-characterized and obtained from previously performed Echocardiography (2D-ECHO) and myocardial perfusion (GSPECT) at rest examination at intervals of no more than 6 months. The outcomes of the study showed (p=0.000) <0.1% and (r = 0.65) thus representing a strong and significant correlation, however there is a lack of consistency between the methods based on the scattering chart that gives (r^2 = 0.42). Bland Altman's illustration state that a good correlation between the methods exists and so does standard deviation for 2D-ECHO and Myocardial perfusion (GSPECT) as demonstrated (50.1±10.8) and (49.1±15.1) respectively. The study showed good overall correlations between EF derived from (2D ECHO) and Myocardial perfusion (GSPECT). In conclusion, the statistics demonstrated that the methods are comparable to each other when measuring EF.

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第21713号 / 薬科博第104号 / 新制||薬科||11(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 小野 正博, 教授 山下 富義, 教授 髙倉 喜信 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22358号 / 医博第4599号 / 新制||医||1042(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長船 健二, 教授 岩田 想, 教授 富樫 かおり / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22363号 / 医博第4604号 / 新制||医||1043(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 富樫 かおり, 教授 上本 伸二 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Introduction: Sentinel lymph node biopsy is an established method used to investigate the riskof lymphatic metastasis especially in breast cancer and melanoma patients. SPECT/ CT isconsidered to be an advantageous method in mapping of sentinel nodes. Aim: The aim of this systematic literature review was to investigate the clinical value ofSPECT/ CT in the detection of sentinel lymph nodes in breast cancer patients. Method: Using specific search terms the database PubMed was used to find studies of potentialrelevance for this systematic review. Criteria for inclusions and exclusion were decided todetermine article relevance. Eligibility of articles was determined according to these criteriawhich lead to the selection of the specific articles included in this study. Results: Eleven studies were included in this systematic review. Seven out of 8 studies foundhigher identification rates of sentinel lymph nodes with SPECT/ CT in comparison to planarlymphoscintigraphy. SPECT/ CT could detect additional lymph nodes in 9 out of 9 studies.SPECT/ CT detected additional extra-axillary lymph nodes in 6 out of 7 studies. SPECT/ CTdetected lymph nodes in 9 out of 9 studies where planar lymphoscintigraphy was negative.Information from additional SPECT/ CT lead to changes in surgical treatment plan in 4 out of4 studies. None of the included studies contained information about change in oncologicaltreatment plan due to findings on SPECT/ CT. Conclusion: SPECT/ CT is an imaging technique with much potential as it seems to allow amore accurate SLN mapping and more precise anatomical localization of SLN in breast cancerpatients, specifically in certain clinical situations. Despite this however, the impact of SLNmapping through SPECT/ CT on patient prognosis remains uncertain.

L’hypoxie est connue pour être responsable d’une propagation tumorale accrue. En conséquence, les tumeurs hypoxiques nécessitent un diagnostic rapide et précis. L’accès à toutes les localisations tumorales par l’imagerie nucléaire est devenu un intérêt majeur pour l’orientation thérapeutique. Dans la première partie de ce manuscrit, un nouveau traceur de l’hypoxie tumorale marqué au technétium 99m a été développé avec succès. De nouveaux traceurs organosilylés marqués au fluor 18 ont également été étudiés. Un second travail a porté sur le développement d’une nouvelle stratégie de fluoration nucléophile pour la préparation de traceurs TEP. Des essais synthèse du Fluorodésoxyglucose ont été réalisés. L’élaboration de cette stratégie a également conduit au développement d’une nouvelle méthodologie de synthèse de dérivés d’acides sulfoniques par déprotection de thiols au moyen d’hypochlorite de tert-butyle. / It has been recognized that hypoxia plays a major negative role in overall tumor progression. The identification and quantitative estimation of tumor hypoxia by means of nuclear imaging is an important factor in planning the therapeutic strategy for a better clinical outcome. In the present work, a new 99mTc tracer for imaging tumor hypoxia has been successfully developed. New organosilicon fluorinated derivatives were also studied. Every synthesized compounds incorporated a nitroimidazole moiety, which is selectively trapped in hypoxic cells. The second part of this work, led to the development of a new nucleophilic fluorination strategy for the preparation of PET tracers. The new strategy was attempted for the preparation of Fluorodeoxyglucose. In the course of this study, a novel oxidative deprotection method of thiols was developed. Herein was described, the synthesis of sulfonic acid derivatives by oxidative deprotection of thiols using tert-butyl hypochlorite.