Objective: To determine the association between perceived stress and the presence of musculoskeletal disorders in physicians at La Caleta de Chimbote Hospital and Eleazar Guzmán Barrón Regional Hospital in Ancash, Peru. Methods. An exploratory cross-sectional analytical study was conducted in 116 physicians. The Nordic Questionnaire was used to determine the areas of musculoskeletal pain and the Perceived Stress Scale (PSS-10) to assess the level of stress. The sociodemographic and occupational characteristics of the population were evaluated from the measurement of proportions and measures of central tendency and dispersion. For the bivariate analysis, Fisher's exact test and Chi2 were used. Finally, the multivariate analysis, based on a Logistics Regression model, was calculated with the crude and adjusted Odd Ratio (OR) [95% Confidence Intervals (CI)]. Results: The responses of 71 evaluations from a group of people between ages 34 to 59 (median 48) with a higher predominance of males (72%) were analyzed. No statistically significant association was found between the presence of non-specific musculoskeletal disorders and the perception of stress (p = 0.066); However, cervical, lumbar, hip / leg and ankle / foot pain specifically did show a significant association (p = 0.009; p = 0.033; p = 0.033 and p = 0.034, respectively). Finally, the cervical area maintained its association when performing the crude analysis and adjusted to physical activity (ORc = 7.29; 95% CI = 1.51-35.21 / ORa = 7.29 95% CI = 1.25-42.37). Anatomical areas such as lumbar, hip / leg and ankle / foot showed a non-significant association when performing the multivariate analysis. / Objetivo: Determinar la asociación entre el nivel de estrés percibido y la presencia de trastornos musculoesqueléticos en médicos del hospital La Caleta de Chimbote y Hospital Regional Eleazar Guzmán Barrón en Ancash, Perú. Métodos. Se realizó un estudio exploratorio de tipo transversal analítico en 116 médicos. Se utilizó el cuestionario nórdico para determinar las zonas de dolor musculoesqueléticos y la Escala de Estrés Percibido (EEP-10) para valorar el nivel de estrés. Se evaluaron las características sociodemográficas y ocupacionales de la población a partir de la medición de proporciones y medidas de tendencia central y dispersión. Para la realización del análisis bivariado se utilizó la prueba exacta de Fisher, Chi2. Finalmente, el análisis multivariado, a partir de un modelo de Regresión de Logística, se calculó con el Odd Ratio (OR) crudo y ajustado [Intervalos de Confianza (IC) al 95%]. Resultados: Se analizaron las respuestas de 71 evaluaciones de un grupo de personas de entre 34 a 59 años (mediana 48) con mayor predominio del sexo masculino (72%). No se encontró asociación estadísticamente significativa entre la presencia de trastornos musculoesqueléticos de manera inespecífica y la percepción de estrés (p=0.066); sin embargo, el dolor cervical, lumbar, cadera/pierna y tobillo/pie específicamente sí mostraron asociación significativa (p=0,009; p=0.033; p=0.033 y p=0.034, respectivamente). Finalmente, la zona cervical mantuvo su asociación al realizar el análisis crudo y ajustado a la actividad física (ORc=7.29; IC95%=1.51-35.21 / ORa=7.29 IC95%=1.25-42.37). Zonas anatómicas como lumbar, cadera/pierna y tobillo/pie mostraron asociación no significativa al realizar el análisis multivariado. / Tesis

No description available.

Die vorliegende Arbeit diente vor allem der Untersuchung, ob es im Gehirn vergleichbare Lymphabflusswege wie im übrigen Körper gibt und falls dies zutrifft, wo diese Abflusswege des Gehirns verlaufen. Denn für größere Proteine und Moleküle müsste es eine geeignete Route geben, um das ZNS verlassen zu können, da diese zum Passieren der Bluthirnschranke (BHS) zu groß sind. In dieser Arbeit konnte erstmals gezeigt werden, dass es auch eine Art lymphatischen Drainageweg aus der Hypophyse (HVL = Adenohypophyse) zu den tiefen und superfizialen, zervikalen Lymphknoten gibt. Daneben konnten auch die Abflussrouten des CSF und über die Nase bestätigt werden. Darüber hinaus wurde versucht zu ermitteln, wie schnell über die jeweiligen Drainagemöglichkeiten extrazelluläre Substanzen und Flüssigkeiten (Liquor) aus dem Gehirn gelangen und weiter in die peripheren Lymphknoten des Halses abtransportiert werden können. Hierbei sollte auch dargestellt werden, ob diese Mechanismen nur passiven Vorgängen zuzuordnen sind, oder ob es auch Hinweise auf aktive, zellulär gesteuerte Prozesse gibt. Wahrscheinlich spielen hier Makrophagen, die hirneigene Proteine und Antigene aufnehmen und in Lymphknoten transportieren und präsentieren, eine wesentliche Rolle. Obwohl es die BHS gibt, die als eine physiologische Barriere- und Filterfunktion zwischen dem Blutkreislauf und dem ZNS fungiert, existieren dennoch autoimmun bedingte Krankheitsbilder des ZNS wie die Autoimmun-Hypophysitis oder die MS. Es ist daher wahrscheinlich, dass es möglicherweise auch mehrere Mechanismen (passiv und aktiv) geben könnte, über die hirneigene Proteine und Substanzen aus dem Gehirn zu den Lymphknotenstationen gelangen können. Über das Lymphsystem wäre wiederum eine Aktivierung des Immunsystems naheliegend, sodass die aus dem ZNS entstammenden Proteine eine Immunantwort initiieren und so autoimmune Krankheitsprozesse einleiten könnten. Für das Verständnis von Erkrankungen wie der MS, der Autoimmunhypophysitis oder aber auch des Morbus Alzheimer wären genauere Kenntnisse über die funktionellen Hintergründe eines „hirneigenen lymphatischen Systems“ von großer klinischer und therapeutischer Relevanz. Auf der Grundlage der Ergebnisse dieser Arbeit könnte das Entstehen von Autoimmunerkrankungen des ZNS und eben auch der Hypophyse eine Erklärung finden, da auch Antigene dem Immunsystem über die beschriebenen Abflusswege zu den peripheren Lymphknotenstatioen des Halses gelangen und präsentiert werden können. Weiterhin besteht die Vermutung, dass zusätzlich auch Makrophagen aktiv durch ihre antigenpräsentierenden Eigenschaften an solchen Immunreaktionen beteiligt sind, jedoch sehr wahrscheinlich in verzögerter Weise im Vergleich zu den schnelleren passiven Drainagerouten des ZNS.

Thesis (M. Tech.) -- Central University of Technology, Free State, 2008 / Motivated by the challenges associated with demonstrating the cervicothoracic junction, a study was conducted at Pelonomi Regional Hospital from May 2006 to June 2007. In this study, two projections of the cervicothoracic junction were done, with the only difference between them being the orientation of the arms. One projection was done using the swimmer’s projection and the other using an adaptation of the swimmer’s projection where the orientation of the arms was reversed. The sample, consisting of 45 patients, was referred from the emergency department and wards. Most of the patients (95.5%) were examined using a computed radiography system providing digital images that were printed using a laser film printer. Other patients were examined using conventional film/screen systems. The objectives of this study were to compare the two imaging techniques with reference to diagnostic quality of the projections, diagnosis of pathology and repeat rate. Radiographers obtained the two projections of the cervical spine; the researcher collected the images and distributed these to three participating radiologists on a rotational basis. The radiologists evaluated the films using a set of criteria; a biostatistician analysed the results of these evaluations. In all the criteria of image quality the swimmer’s projection showed better results. There were also, however, instances where the adapted swimmer’s had better results. The differences in percentages were not significant enough to show any statistical difference between the resultant images of the two techniques. No valid deduction could be made in relation to the demonstration of pathology due to variable instances of pathology evaluated by the radiologists. The repeat rate of the adapted swimmer’s projection compared well with the swimmer’s projection. Though the swimmer’s projection had better results for most of the criteria used in this study, no unequivocal, statistically significant evidence of it demonstrating C7-T1 better could be found. What was evident was the validity of the adapted swimmer’s projection as an alternative under certain conditions. Knowing that there is an alternative method to visualising the C7- T1 junction could be beneficial not only to radiography, but also to our patients. In cases where the swimmer’s projection is not possible due to extremity injuries, an alternative arm orientation can be useful. The alternative can also address the problem regarding multiple repeats of the swimmer’s projection.

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Introduction Cisplatin has been widely used to treat solid tumours and much success has come from the use of this drug in the treatment of head and neck, ovarian, testicular, cervical and small-cell lung cancers. However, the success of cisplatin treatment is limited due to its dose-limiting toxicity and its resulting side-effects, such as nephro- and ototoxicity. The devastating side-effects induced by cisplatin treatment provided the platform for this study whereby the aim was to lower the concentration of cisplatin while maintaining its cancer-specific cytotoxic action. Equally concerning is, cisplatin resistance which is becoming increasingly common, and this radically limits the clinical efficacy and utility of the drug. Adjuvant therapy has thus become necessary in an attempt to possibly curb or lessen the extent of cisplatin resistance. Due to the large body of evidence implicating the importance of autophagy in cancer, the prospect of targeting this mechanism has generally been accepted. Various chemotherapy agents induce autophagy in cancer cells; however the effect of cisplatin on autophagic induction has not been very well explored. We thus hypothesise that the manipulation of the autophagic pathway will sensitise cancer cells to a low concentration of cisplatin treatment. Furthermore, due to the functional interaction between Bcl-2 and Beclin-1 and its role in the regulation of autophagy, ratio analysis of Beclin-1 to Bcl-2 as means of detecting the role of autophagy within the cell under homeostatic and treatment/stress conditions has been conducted. Additionally, Bcl-2 has a prominent role in the malignant cell and it’s over-expression has been found to confer resistance in a variety of cancerous cell lines. We therefore hypothesise that the silencing of Bcl-2 prior to cisplatin treatment will sensitise cervical cancer cells to apoptosis and increase the Beclin-1/Bcl-2 ratio in favour of apoptosis. Materials and Methods Three human cervical cell lines were used: a non-cancerous ectocervical epithelial cell line (Ect1/E6E7) and two cancerous cervical cell lines (HeLa and CaSki). In order to determine a concentration of cisplatin that was non-toxic to the non-cancerous Ect1/E6E7 cell line, a dose-response was performed. With the use of an autophagy inhibitor (bafilomycin A1) and an autophagy inducer (rapamycin), autophagic flux capacities were assessed in each cell line through the Western blotting technique. In order to assess whether the chosen concentration of cisplatin induced autophagy, flow cytometry with the use of a Lysotracker™ dye was utilised, as well as analysis of autophagy protein levels (LC-3 II, Beclin-1 and p62). Autophagy modulation was achieved through two methods: pharmacological modulation with use of two recognised agents, namely bafilomycin A1 and rapamycin, and biological manipulation with the use of ATG5 and mTOR mRNA silencing. The effects of different treatment regimes on cell death was assessed with the use of PARP and caspase-3 cleavage through Western blotting, caspase-3/-7 activity (Caspase-Glo®), PI inclusion, LDH release and MTT reductive capacity. Additionally the effects of these treatment regimes on cell-cycle progression were also analysed. Beclin-1 and Bcl-2 expression was determined through Western blotting and immunocytochemistry before and after treatment with cisplatin in HeLa and CaSki cells. To assess the reliance of the cervical cancer cells on Bcl-2 after cisplatin treatment, Bcl-2 knock-down was achieved through RNA interference, where after the Beclin-1/Bcl-2 ratio was assessed as well as apoptosis with the use of cleaved PARP analysis (Western blotting) and Caspase-Glo©. For the ex vivo analysis, biopsies were collected from patients undergoing routine colposcopy screenings and hysterectomies at Tygerberg Hospital, Tygerberg, Western Cape. A total of 10 normal, 29 low-grade squamous intraepithelial lesions (LSIL), 33 high-grade squamous intraepithelial lesions (HSIL) and 13 carcinoma biopsies were collected for analysis, where after the expression profiles of two autophagy markers (mTOR and LC-3 II), as well as one anti-apoptotic marker (Bcl-2) were assessed. Protein levels were analysed through Western blot and confirmed through immunohistochemistry. Results Dose-response curves revealed that 15 μM of cisplatin did not induce cell death in the normal cervical epithelial cell line (Ect1/E6E7) and was therefore utilised through-out the remainder of the study. It was additionally determined that the CaSki cells were more resistant to cisplatin treatment when compared to the HeLa and Ect1/E6E7 cells. Autophagic flux analysis revealed that, although all three cell lines were cervix derived, their autophagic flux capacities differed. It was observed that the chosen concentration of cisplatin was able to induce autophagy in all three cell lines, with the HeLa cells demonstrating a particularly pronounced response. Autophagy modulation in conjunction with cisplatin treatment revealed the following: Autophagy inhibition with bafilomycin A1 lead to significant increases in caspase-3 and PARP cleavage and LDH release in both cervical cancer cell lines. The inhibition of autophagy through silencing of ATG5 induced caspase-3 cleavage and agrees with results obtained from pharmacological inhibition of autophagy with bafilomycin A1. In addition to autophagic induction, a low concentration of cisplatin induced the up-regulation of Bcl-2, which when silenced significantly improved cisplatin-induced apoptosis in both cervical cancer cell lines. Analysis of the expression profiles of mTOR and LC-3 in normal, pre-malignant (LSIL and HSIL) and cancerous cervical tissue revealed that autophagy is significantly up-regulated in HSILs and carcinoma of the cervix. Additionally, Bcl-2 expression is significantly increased in cervical carcinoma tissue, which agrees with results from other studies. Conclusion Autophagic flux capacities between the three cell lines investigated, derived from the same organ, differ significantly. This should be taken into consideration when autophagic modulation is being used as an adjuvant treatment. With regard to chemotherapy treatment in cervical cells, a low-concentration of cisplatin significantly induces autophagy in malignant and non-malignant cervix-derived cell lines where it serves a pro-survival mechanism. Inhibition of autophagy with bafilomycin A1 and ATG5 siRNA confirmed this survival effect in both cancerous cell lines where apoptosis was significantly increased. Interestingly, rapamycin pre-treatment together with cisplatin did not induce significant levels of apoptosis in HeLa cells where autophagy induction may have provided additional protection from the cytotoxic effects of cisplatin. Therefore the inhibition of autophagy through pharmacological and biological inhibition improves the cytotoxicity of a low concentration of cisplatin and provides a promising new avenue for the future treatment of cervical cancer. Bcl-2 up-regulation in response to cisplatin treatment also serves as a protective mechanism by which cervical cancer cells survive. The extent of apoptotic cell death observed after biological inhibition of Bcl-2 reiterates the fact that this response may be exploited in order to favour the use of lower concentrations of cisplatin. Analysis of clinical specimens emphasised the value of the in vitro work: Cervical cancer biopsies had increased expression of both LC-3 II and Bcl-2, indicating autophagy induction and apoptosis inhibition, respectively. Thus two novel methods of improving cisplatin cytotoxicity have been demonstrated in the following study. Treatment regimens may administer more frequently and prolonged due to the minimal side-effects that accompanies low-dose cisplatin treatment. / AFRIKAANSE OPSOMMING: Inleiding Sisplatien word algemeen gebruik vir die behandeling van soliede gewasse. Baie sukses is reeds deur die gebruik van díe middel behaal in die behandeling van kop en nek, ovariale, terstikulêre, servikale en klein-sel kankers. Die sukses van Sisplatien-behandeling word wel ingeperk deur die dosis-beperkende toksisiteit en die gevolglike newe-effekte soos nefrotoksisiteit. Hierdie verwoestende newe-effekte wat deur sisplatien behandelings geïnduseer word, het as die platform vir hierdie studie gedien. Die doel was om die sisplatien konsentrasies te verlaag, maar terselfdertyd die kankerspesifieke sitotoksisiteit te behou. Nog ʼn punt van kommer is dat sisplatien-weerstandigheid aan die toeneem is, wat die kliniese effektiwiteit en gebruik van hierdie middel geweldig beperk. Byvoegmiddels het dus noodsaaklik geraak in die poging om die sisplatien-weerstandigheid te verhoed. As gevolg van verskeie bewyse wat die belangrikheid van outofagie in kanker impliseer, is die vooruitsig om hierdie meganisme te teiken, algemeen aanvaar. Verskeie chemoterapeutiese middels induseer outofagie in kanker selle, hoewel die effek van Sisplatien op outofagiese induksie nog nie goed ondersoek is nie. Ons hipotese is dus dat die manipulasie van die outofagiese pad die kankerselle sensitiseer tot ʼn lae konsentrasie van sisplatien. Verder, as gevolg van die funksionele interaksie tussen Bcl-2 en Beclin-1, en hul rol in die regulering van outofagie, is verhouding-analises van Beclin-1 tot Bcl-2 uitgevoer met die doel om die rol van outofagie in die sel onder homeostatiese en behandeling/stres kondisies te bepaal. Verder is Bcl-2 bekend daarvoor om ʼn prominente rol te speel in kwaadaardige selle, en die ooruitdrukking daarvan is gevind om weerstandigheid aan te help in ʼn verskeidenheid van kankeragtige sellyne. Ons hipotetiseer dus dat geenonderdrukking van Bcl-2 voor die behandeling met sisplatien die servikale kanker selle sal sensitiseer tot apoptose en ʼn verhoging in die verhouding van Beclin-1/Bcl-2 veroorsaak, wat in die guns van apoptose is. Materiale en Metodes Drie menslike servikale sellyne was gebruik: ʼn nie-kankeragtige servikale epiteel sellyn (Ect/E6E7) en twee kankeragtige servikale sellyne (HeLa en CaSki). Om ʼn konsentrasie van sisplatien te bepaal wat nie-toksies tot die nie-kankeragtige Ect1/E6E7 sellyn is, was ʼn dosisrespons uitgevoer. Met die gebruik van ʼn outofagiese inhibeerder (bafilomycin A1) en ʼn outofagiese induseerder (rapamycin), is die outofagiese-fluks kapasiteite van elke sellyn deur die Western Blotting tegniek geassesseer. Om te bepaal of die gekose konsentrasie van sisplatien outofagie induseer, is vloeisitometrie met ʼn Lysotracker™ kleurstof gebruik, sowel as analises op outofagie proteïenvlakke (LC-3 II, Beclin-1 en p62). Outofagie modulering is behaal deur twee metodes: farmakologiese modulering met twee erkende middels, naamlik bafilomycin A1 en rapamycin, en biologiese manipulasie met die gebruik van ATG5 en mTOR geenonderdrukking. Die effekte van die verskillende behandeling skedules op seldood was geassesseer deur gebruik te maak van PARP en kaspase-3 splitsing deur Western Blotting, kaspase-3/-7 aktiwiteit deur Caspase-Glo ®, PI-insluiting, LDH vrystelling en MTT reduserende kapasiteit. Verder is die effekte van hierdie behandeling skedules op selsiklus progressie ook geanaliseer. Beclin-1 en Bcl-2 uitdrukking was ook bepaal deur Western Blotting en immunohistochemie voor en na behandeling met sisplatien in HeLa en CaSki selle. Om die afhanklikheid van die servikale kankerselle op Bcl-2 na sisplatien behandelings te toets, is Bcl-2 onderdruk deur RNA-inmenging, waarna Beclin-1/Bcl-2 verhouding geassesseer is, sowel as opoptose deur die gebruik van gesplitste PARP analises (Western Blotting) en Caspase-Glo©. Vir die ex vivo analises is biopsies vanaf pasiënte wat roetine kolposkopie en histerektomies ondergaan, verkry (Tygerberg Hospitaal, Tygerberg, Westelike Provinsie). ʼn Totaal van 10 normale, 29 lae-graad plaveisel intraepiteel letsels (LSIL), 33 hoe-graad plaveisel intraepiteel letsels (HSIL) en 13 karsinoom biopsies is verkry vir analises. Die uitdrukkingsprofiel van twee outofagiese merkers (mTOR en LC-3 II), asook een merker vir apoptose (Bcl-2), was geassesseer. Proteïen vlakke was ook deur Western Blotting geanaliseer en deur immunohistochemie bevestig. Resultate Dosisrespons kurwes het getoon dat 15 μM sisplatien nie seldood in die normale sellyn (Ect1/E6E7) geïnduseer het nie, en was daarom gebruik deur die res van hierdie studie. Verder is daar ook gevind dat CaSki selle meer weerstandig tot sisplatien behandelings is wanneer vergelyk word met die HeLa en Ect1/E6E7 selle. Outofagiese-fluks analises het getoon dat, alhoewel al drie sellyne vanaf die serviks afkomstig is, daar verskille is in hul outofagiese-fluks kapasiteit. Daar is ook waargeneem dat die gekose konsentrasie van sisplatien in staat was om outofagie te induseer in al drie sellyne, met HeLa selle wat die mees merkbare respons getoon het. Modulering van outofagie in samewerking met sisplatien behandelings het die volgende onthul: inhibisie van outofagie deur bafilomycin A1 het gelei tot ʼn beduidende verhoging in kaspase-3, PARP splitsing en LDH vrylating in beide servikale kankersellyne. Geenonderdrukking van ATG5 induseer kaspase-3 splitsing en stem ooreen met resultate wat verkry is deur farmakologiese inhibisie van outofagie met bafilomycin A1. Bykomend tot outofagiese indusering, het ʼn lae konsentrasie sisplatien die opregulering van Bcl-2 geïnduseer. Wanneer Bcl-2 geenonderdrukking in hierdie scenario toegepas was, het dit ʼn beduidende verbetering in sisplatien-geïnduseerde apoptose in beide servikale kankersellyne getoon. Analises van die uitdrukkingsprofiel van mTOR en LC-3 in normale, pre-maligne (LSIL en HSIL) en kankeragtige servikale weefsel, het getoon dat outofagie beduidend opgereguleer is in HSILs en servikale karsinome. Verder is Bcl-2 uitdrukking ook gevind om beduidend verhoog te wees in servikale karsinoomweefsel, wat ooreenstem met resultate verkry in ander studies. Gevolgtrekking Outofagiese-fluks kapasiteite tussen die drie sellyne, afkomstig van dieselfde orgaan, toon beduidende verskille. Hierdie bevinding moet in ag geneem word wanneer outofagiese-modulering as ʼn bevorderingsbehandeling gebruik word. Met betrekking tot chemoterapie behandeling in servikale selle; ʼn lae konsentrasie van sisplatien veroorsaak ʼn beduidende indusering van outofagie in kwaadaardige en nie-kwaadaardige serviks-afkomstige sellyne, en dien as ʼn oorlewingsmeganisme. Inhibisie van outofagie met bafilomycin A1 en ATG5 siRNA het hierdie beskermings effek bevestig, aangesien apoptose beduidend verhoog was in beide kankersellyne. Interessant genoeg het rapamycin pre-behandeling tesame met sisplatien nie beduidende vlakke van apoptose in HeLa selle geïnduseer nie. Outofagie induksie mag dalk addisionele beskerming teen die sitotoksiese effekte van sisplatien gebied het. Daarom het die inhibisie van outofagie deur farmakologiese en biologiese inhibering die sitotoksisiteit van ʼn lae konsentrasie sisplatien bevorder, wat ʼn belowende bevinding is vir die toekomstige behandeling van servikale kanker. Bcl-2 opregulering as gevolg van sisplatien behandelings dien ook as beskermings meganisme waarby servikale kankerselle oorleef. Die mate van apoptotiese seldood wat waargeneem word na biologiese inhibering van Bcl-2, wys weer op die feit dat hierdie respons uitgebuit kan word vir die gebruik van laer konsentrasies van sisplatien. Analises van die kliniese monsters het ook die waarde van die in vitro werk versterk: Servikale kanker biopsies het verhoogde uitdrukking van beide LC-3 II en Bcl-2 getoon, wat aandui dat outofagie geïnduseer en apoptose geïnhibeer word. Daar is dus twee nuwe metodes vir die verbetering van sisplatien-toksisiteit in hierdie studie gedemonstreer. Behandeling regimes kan meer gereeld en vir langer tydperke toegepas word, aangesien die newe-effekte van lae-dosis sisplatien behandelings minimaal is. / MRC for funding

This study aimed to understand how the identity of Manitobans with early malignancy is affected through diagnosis, decision making and treatment. Using grounded-theory methodology, semi-structured interviews were conducted with 18 adult patients with early breast, colon, lung, prostate and gynecological cancers, before and after adjuvant treatment decision making. 15 adult friends and family members were also interviewed. Significant findings include: 1) After diagnosis, the “cancer identity” emerged as a new aspect of the patient’s identity; 2) Establishing a post-diagnosis routine was a significant source of distress for patients; 3) Ability to re-establish routine post-diagnosis may be enhanced by providing earlier notification of medical appointment times and information regarding how different treatment options will affect the patient’s identity. This study provides new insight into the experience of patients with malignancy in Manitoba. Additionally, it presents recommendations, based on the insights and concerns of its participants, for improving the cancer journey of Manitobans. / May 2017

Bakgrund Extern strålbehandling är en viktig del av processen för behandling av cervikal cancer. Målet med denna typ av behandling är att bestråla tumörområdet med så hög dos som möjligt och omkringliggande frisk vävnad med så lite dos som möjligt. Ett problem som upptäckts är att rörelser i tumörområdet under behandling kan påverka precisionen av strålfältet. Syfte Syftet med litteraturstudien var att beskriva omfattning av rörelse och volymförändring i tumörområdet under strålbehandling av cervikal cancer. Metod                  Nio artiklar med kvantitativ design kvalitetsgranskades och resultaten sammanställdes med inspiration av Fribergs modell. Resultat Omfattning av rörelser och volymförändringar upptäcktes variera och är något som skiljer sig mellan individer. Valet av bildtagnings- och mätmetod har stor betydelse gällande patientsäkerhet och stråldos.   Slutsats Hur mycket tumörområdet rör sig/förändras i volym var något som varierade mellan patienterna i studierna och det är därför viktigt att anpassa behandlingen efter dessa variationer. Olika metoder för bildtagning och mätning kan användas både för att upptäcka rörelser och volymförändringar i tumörområdet under extern strålbehandling. De olika metodernas fördelar bör noggrant vägas mot nackdelar innan användning för att hitta en optimal metod som främjar patientsäkerhet. / Background External radiation therapy is an important part when treating cervical cancer. The goal of this type of therapy is to irradiate the tumor area with the highest possible dose and minimize the dose given to the surrounding healthy tissue. One problem showed is that movement in the tumor area during treatment can cause problems regarding keeping the precision as high as possible. Aim The aim of this literature study was to describe the extent of movement and volume change in the tumor area during external radiotherapy treatment of cervical cancer. Method Nine articles with quantitative design were quality-reviewed and the results were compiled with inspiration from Friberg's model. Results The extent of movements and volume changes was discovered varying and is something that differs between individuals. The choice of imaging and measurement method is of great importance in terms of patient safety and radiation dose. Conclusions The extent of movement and change in volume varied between patients in the studies and it is therefore important to adjust the treatment according to these variations. Different methods of imaging and measurement can be used both to detect movements and volume changes in the tumor area during external radiation therapy. The benefits of the different methods should be carefully weighed against disadvantages before use to find an optimal method that promotes patient safety.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

This critical synopsis of prior work by Clive Beggs is submitted in support of a PhD by published work. The work focuses on venous and cerebrospinal fluid (CSF) anomalies associated with multiple sclerosis (MS) and other neurological diseases. MS is characterized by focal inflammatory lesions, which are often venocentric. Recently a vascular syndrome, chronic cerebrospinal venous insufficiency (CCSVI) has been linked with MS. This syndrome, which is characterized by constricted cerebral venous outflow, has become mired in controversy, with various studies producing conflicting findings, with the result that the science associated with CCSVI has become obscured. Clive Beggs work seeks to bring clarity to the debate surrounding CCSVI by characterizing physiological changes associated with constricted cerebral venous outflow. The work submitted here involves collaborative studies with Robert Zivadinov (University of Buffalo), Paolo Zamboni (University of Ferrara), and Chih- Ping Chung (National Yang Ming University of Medicine). The key findings of these studies are: (i) MS patients, diagnosed with CCSVI, exhibit greatly increased hydraulic resistance of the cerebral venous drainage system; (ii) MS patients experience loss of the small cerebral veins; (iii) MS patients exhibit reduced CSF bulk flow, consistent with mild venous hypertension; (iv) MS patients exhibit increased CSF pulsatility in the Aqueduct of Sylvius, which appears to be linked with mild venous hypertension associated with CCSVI; and (v) jugular venous reflux is associated with white matter and parenchymal volumetric changes in Alzheimer’s patients. Collectively, these findings suggest that extracranial venous anomalies are associated with changes in the intracranial physiology.

Le cancer du col représente un problème de santé publique au Marco. L’objectif principal de cette thèse est d’améliorer les connaissances sur le cancer du col de l’utérus au Maroc en terme d’épidémiologie descriptive et analytique notamment par l’étude des principaux facteurs associés à ce cancer, son retard de diagnostic et sa prise en charge.Méthodologie Pour répondre à notre objectif, trois études ont été menées. La première étude, rétrospective sur dossier d’hospitalisation, sur les stades de diagnostic et les résultats des traitements du cancer du col. La deuxième étude, transversale, sur les facteurs liés au retard de diagnostic du cancer du col et la troisième étude, cas-témoins multicentrique avec appariement individuel sur l’âge, sur les facteurs de risque du cancer du col de l’utérus. Résultats La première étude a montré la vulnérabilité socioéconomique de la population des femmes atteintes de cancer du col et a mis le point sur les problèmes du retard de diagnostic et de l’accessibilité aux établissements de soins auxquels elles sont confrontées. L’étude a mis l’accent sur la durée du suivi insuffisante et le nombre élevé des perdues de vue. La deuxième étude, a montré que les femmes âgées de moins de 50 ans, analphabètes, non mariées, les femmes au foyer, les femmes résidant en milieu rural, les femmes résidant à plus de 100Km du lieu du diagnostic du cancer, les femmes sans antécédents de cancer du col et les femmes n’ayant pas eu comme premier symptôme des saignements gynécologiques étaient plus à risque du retard de diagnostic du cancer du col. L’étude cas-témoins a confirmé que l’infection à HPV est le facteur de risque majeur du cancer du col. Les autres facteurs de risque du cancer invasif du col utérin étaient : la parité élevée, le faible niveau d'éducation, l’existence de multiples partenaires sexuelles chez le mari, les rapports sexuels pendant les menstruations et les antécédents d’IST. La limite majeure de notre étude cas-témoins est liée au manque de puissance statistique pour l’étude de l’association avec d’autres facteurs tels que les facteurs nutritionnels. Conclusion Les études réalisées dans le cadre de notre thèse, en dépit de leurs limites, constituent une source d’information pour la recherche scientifique sur le cancer du col au Maroc et dans les pays similaires. Elles contribuent à l’amélioration des connaissances sur le cancer du col au Maroc et par là des attitudes et pratiques des différents corps sanitaires vis-à-vis de ce cancer. Elles ont permis de définir les populations à risque de cancer du col et à risque de retard de diagnostic et, ainsi de mieux les cibler dans les programmes de dépistage d’information et d’éducation. Les résultats de nos travaux de recherche pourraient représenter une « situation de référence » utile pour tout programme d’évaluation concernant le cancer du col au Maroc. Ceci devrait permettre dans le futur de mieux évaluer à long terme l’efficacité des programmes de dépistage, de vaccination, des traitements et de l’éducation pour la santé. / The main objective of this work was to improve knowledge about cervical cancer in Morocco in terms of descriptive and analytical epidemiology including the study of the main factors associated with cancer, the delay in diagnosis and its management. Methods : To meet our objectives, we conducted three studies. The first (Study of diagnosis stages and treatment outcomes for cervical cancer), is a retrospective study using data from hospital records of patients with cervical cancer in the major cancer centers in Morocco. The second study (Study of factors related to delay in diagnosis of cervical cancer), transversal, with recruitment of cervical cancer patients. The third study (Study of risk factors for cervical cancer) was a multicenter case-control study with individual matching on age. Results : The first study showed the socio-economic vulnerability of the population of women with cervical cancer and the problems of delayed diagnosis and access to health facilities. In addition, this study focused on the inadequate length of the follow-up and the high number of lost to following-up. The second study showed that women aged less than 50 years, illiterate, unmarried, women at home, women living in rural areas, women living more than 100km from the place of cancer diagnosis, women without history of cervical cancer and women who have not had, as the first symptom, a gynecological bleeding were more at risk of delayed diagnosis of cervical cancer. The case-control study confirmed that HPV infection is the major risk factor for cervical cancer. The other risk factors for invasive cervical cancer identified in our study were: the high parity, the low educational level, husband's multiple sexual partners, sex during menstruation and the history of venereal diseases. Conclusion : The studies conducted in the context of our thesis, inspite of their limitations, are considered as a rich source of information for scientific research on cervical cancer in Morocco and in similar countries. They have improved the knowledge on cervical cancer in Morocco and thus should improve the knowledge, attitudes and practice of different health practitioner’s for cervical cancer. They helped to define population at risk of cervical cancer and of delayed diagnosis. Therefore, it allows them to be better targeted by the screening, information and education programs. The results of our research also represent a "reference situation" for any evaluation program for cervical cancer in Morocco. This should help, in the future, to better assess the long-term effectiveness of screening programs, vaccination, treatment and health education.