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The present study was performed to determine if pigs varying in their susceptibility to stress, adapted to a casein-based diet, experience an improvement in biochemical parameters related to stress and behaviour compared to pigs adapted to the traditional western canadian cereal-based swine diet. Experiment 1 involved separating fifty-eight, 8-week old pigs according to genotype with respect to the halothane gene. Within each genotype pigs were divided into 2 groups and assigned to either a control diet or to a diet where most of the protein source was substituted for casein. All animals were adapted to diet for 6 weeks and experienced a weekly blood sampling stressor. Day 1, 14 and 35 of the plasma samples were analyzed for glucose, cortisol, ACTH, insulin, pyridoxal 5$ sp prime$-phosphate (PLP), amino acid concentrations and dopamine-$ beta$-hydroxylase (DBH) activity; metabolic indices known to be responsive to stress. Experiment 2 involved separating fifty-seven, 14-week old pigs in the same manner, then adapting the pigs to their respective diets for a period of 4 weeks. Afterwards, pigs were transferred from their pen to a novel pen-maze situation where they had their behaviour monitored for a period of one hour. Results of these experiments have revealed that (1) the stress susceptible and carrier pigs experienced reduced day 35 plasma glucose, PLP concentrations and DBH activity compared to normal pigs; (2) dietary adaptation to the casein diet resulted in greater day 14 and 35 PLP levels and day 35 essential amino acid lysine, threonine, methionine, tryptophan and arginine concentrations compared to control-adapted pigs; (3) the carrier pigs investigated their surroundings more frequently than the stress susceptible pigs, and the normal pigs engaged in the through-maze behaviour more often than the stress susceptible pigs; and (4) adaptation to the casein diet, compared to the control diet, resulted in fewer displacement-type behaviours such as drinking

BACKGROUND: Malignant and paramalignant pleural effusions are important complications of many malignancies. The two main management options debated in the literature are: 1) insertion of an indwelling pleural catheter (IPC) to achieve chronic drainage of the effusion, or 2) hospitalization with tube thoracostomy and subsequent chemical pleurodesis (CP) with talc or doxycycline to prevent fluid reaccumulation. We aimed to describe a large series of patients with malignant pleural effusions managed with an IPC, identify and validate factors identified in the literature as predictors of spontaneous pleurodesis in the IPC group and compare the group managed with IPC to patients managed with CP. METHODS: We designed a retrospective cohort study comparing patients with malignant and paramalignant pleural effusions managed either with CP between March 1, 2003 and February 28, 2006 or IPC insertion between May 1, 2006 and April 1, 2009. The CP group was identified through the prescription of talc or doxycycline and the IPC group from the IPC clinic database. Data were collected from paper and electronic records and from the Government of Ontario. RESULTS: We identified 193 consecutive patients with an ECOG performance status of less than 4 (ECOG less than 4 means that the patient is not completely disabled and confined to bed or chair) having undergone IPC insertion and 168 who were managed with CP. None of the variables we tested were significant predictors of spontaneous pleurodesis in the IPC group. Pleural effusion control rates at 6 months were higher in the IPC group than in the CP group (52.7% vs 34.0%, p<0.01) but the rate of freedom from pleural effusion at 180 days and catheter removal at 90 days was not significantly different (25.8% in the IPC group and 34.0% in the CP group p=0.14). Patients in the IPC group had a significantly longer median survival (148 days measured from the date of catheter insertion vs 133 days in the CP group, log-rank p<0.05). CONCLUSION: We found an intriguing possible survival benefit favouring management of malignant or paramalignant effusions with an IPC. Given possible biases due to the design of this study and uncertain explanatory mechanism, this needs to be confirmed in a randomized controlled trial. Quality of life, an important measure of success for these palliative procedures, should also be measured.

Malignant hyperthermia is a potentially fatal pharmacological disorder and is triggered by volatile anaesthetics in predisposed individuals. Mutations in the RYR1 gene, encoding the skeletal muscle calcium receptor channel have been linked to MH susceptibility. Over 200 point mutations have been have been found to date in the RYR1 gene linked to MHS worldwide. EBV-immortalization is regularly used worldwide as an effective procedure for inducing long-term growth of human B lymphocytes. In the current study, it was observed that immortalized lymphocytes from MHS patients heterozygous for the missense mutation H4833Y when initially cultured expressed both wild type and mutant allele but after a few weeks of culture they seemed to lose the mutant allele. High resolution melting assays and hybridization probe assays showed the loss of heterozygosity and this was confirmed using DNA sequencing. Genotyping and haplotype analysis using three intragenic RFLPs and two (CA)n repeat microsatellite markers tightly linked to the RYR1 gene showed a definite change in the haplotype, suggesting more widespread changes in the genome upon short-term culture of EBV-immortalized B-lymphocytes

Malignant hyperthermia (MH) is a rare pharmacogenetic disorder in humans induced by volatile anaesthetics and depolarising muscle relaxants. An MH reaction shows abnormal calcium homeostasis in skeletal muscle leading to a hypermetabolic state and increased muscle contracture. A mutation within the skeletal muscle calcium release channel ryanodine receptor gene (RYR1) is associated with MH and is thought to cause functional defects in the RYR1 channel leading to abnormal calcium release to the sarcoplasm and consequent MH reactions. Mutations within RYR1 are also associated with a rare congenital myopathy, central core disease (CCD). CCD is characterised by muscle weakness and is thought to be caused by insufficient calcium release from the RYR1 channel during excitation-contraction (EC) coupling. To investigate functional effects of RYR1 mutations, the entire coding region of human RYR1 was assembled and cloned into an expression vector. Mutant clones containing RYR1 mutations linked to MH or CCD were also constructed. Wild-type (WT) and mutant RYR1 clones were used for transient transfection of HEK-293 cells. Western blotting was performed after harvesting and expressed WT and mutant RYR1 proteins were successfully detected. Immunofluorescence showed co-localisation of RYR1 proteins and the endoplasmic reticulum in HEK-293 cells. [3H]ryanodine binding assays showed that RYR1 mutants linked to MH were more sensitive to the agonist 4-chloro-m-cresol (4-CmC) and less sensitive to the antagonist Mg2+ compared with WT. Two C-terminal RYR1 mutants T4826I and H4833Y were very significantly hypersensitive to 4-CmC and they may also result in a leaky channel. This hypersensitivity of mutants linked to MH may result in abnormal calcium release through the RYR1 channel induced by triggering agents leading to MH reactions. RYR1 mutants linked to CCD showed no response to 4-CmC showing their hyposensitive characteristics to agonists. This study showed that the human RYR1 proteins could be expressed in HEK-293 cells. Moreover, using the recombinant human RYR1 clone, a single mutation within RYR1 resulted in a functional defect in expressed RYR1 proteins and functions of mutant RYR1 proteins varied from hypersensitive to hyposensitive depending on the mutation and whether it was linked to MH or CCD.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 4 uppsatser.

Σκοπός της παρούσας διπλωματικής εργασίας είναι η υλοποίηση ενός αποτελεσματικού αλγορίθμου ικανού να επεξεργάζεται οποιεσδήποτε βιοψίες κυττάρων που εμπεριέχουν κακοήθεις νεοπλασίες και να τις αναγνωρίζει. Η επεξεργασία γίνεται κυρίως χρησιμοποιώντας τις χρωματικές ιδιότητες των υπό εξέταση εικόνων. Το αρχικό δείγμα διέρχεται από αρκετά στάδια επεξεργασίας κατά τα οποία αλλάζει τόσο η μορφή του όσο και η χρωματική του δομή. Αρχικός σκοπός είναι η μετατροπή της αρχικής εικόνας σε μορφή που θα επιτρέπει με σαφήνεια την επεξεργασία της. Ο αλγόριθμος που υλοποιήθηκε είναι φιλικός προς τον χρήστη και δίνει την δυνατότητα σε κάθε βήμα να επιλέγει οποιαδήποτε τιμή της παραμέτρου εάν δεν επιθυμεί να ακολουθήσει τις προεπιλεγμένες τιμές. / Aim of present diplomatic work is the implementation of a robust algorithm capable to process any pigmentation biopsies of cells that include malignant neoplasm and finally to recognize them. The process mainly takes place by using the chromatic attributes of the pictures. The initial sample goes through from enough stages at which stage we change both the form and the chromatic structure. Initial aim is the transformation of the initial picture in a form that will allow with clarity the process. The algorithm that was implemented is friendly to the user and it gives the possibility in each step of selecting any price of parameter or if it does not wish it to follow the preselected prices.

Upplevelsen av att leva med maligna tumörsår är unik för varje patient och fysiska symtom som smärta, lukt, läckage, blödning och klåda kan ge upphov till depression och social isolering. Syftet med litteraturstudien var att belysa patienters upplevelse av att leva med maligna tumörsår. En allmän litteraturstudie genomfördes med sju vetenskapliga resultatartiklar som tolkades i en innehållsanalys. Tre teman kunde urskiljas: Leva med en förlorad kropp, Leva med strategier för att hantera lidandet och Leva med en förändrad självbild och livsvärld. Resultatet påvisade en förnekelse över sårets existens hos patienten och ett behov av att dölja såret för sin omgivning. En ständig oro för att såret skulle synliggöras gjorde att patienten medvetet valde bort att uppsöka vård. Upplevelser av skam och att förlora kontrollen över den fysiska kroppen gav upphov till en förändrad självbild hos patienten. Genom samtal kunde patienten återta kontrollen över sin livssituation och bryta isoleringen från omvärlden. Hopp var en stark strategi som bidrog till att patienten återfick sin livskraft. Inom vetenskapen omvårdnad kan sjuksköterskan öka kunskapsunderlaget om existentiella mänskliga behov och begär i patienters levda värld med maligna tumörsår genom akademisk utbildning och forskning som minskar patienters lidande och främjar en evidensbaserad omvårdnadsprocess. / Living with malignant fungating wounds is a unique experience and physical symptoms can lead to depression and social isolation. The aim of the study was to illuminate patients' experiences of living with malignant fungating wounds. A general literature study was conducted by content analysis of seven qualitative articles. Three themes emerged: Living with a lost body, Living with strategies to deal with suffering and Living with a new identity and lifeworld. The result showed a denial of the wound's existence and a need to conceal the wound from its surroundings. A constant concern that the wound would be made visible meant that the patient deliberately chose not to seek care. Experiences of shame and loss of control of the physical body gave rise to a change in the patient's self-identity. Through conversations, the patient was able to regain control over their life situation and break the isolation from the outside world. Hope was a strategy that helped restore the patient's vitality. Within the nursing tradition, the registered nurse can require more knowledge and increase understanding on the existential human needs in these patients' unique lifeworld through further research and academic education to alleviate suffering and promote an evidence-based nursing process.

O carcinoma espinocelular (CEC) de cabeça e pescoço é uma neoplasia maligna de prognóstico desfavorável e baixa taxa de sobrevida. Entender os processos biológicos envolvidos na carcinogênese poderá ser de extrema importância para o desenvolvimento de novas tecnologias de tratamento e melhora do prognóstico em pacientes acometidos pela doença. A maior causa de insucessos clínicos em termos de terapia e prognóstico em pacientes com câncer é a invasão tecidual e o desenvolvimento de potencial metastático. A migração celular é indispensável para a progressão tumoral e as células apresentam motores moleculares desempenhados especialmente pela família da Miosina II não muscular (MNMII). Codificadas por diferentes genes, existem três isoformas conhecidas em células de mamíferos (MNMIIA, MNMIIB, MNMIIC). As MNMIIs estão envolvidas em funções celulares como migração, adesão e citocinese. Sendo o entendimento da migração, adesão celular e citocinese fatores chave na progressão tumoral, e que o a invasão tecidual e o desenvolvimento de potencial metastático são essenciais na definição do prognóstico dos pacientes, o objetivo deste estudo foi descrever o perfil e exposição à fatores de risco como álcool e fumo dos pacientes diagnosticados com CEC de cabeça e pescoço, graduação histológica, parâmetros clínicos tumorais (TNM), padrão de expressão das isoformas de MNMII (MNMIIA, MNMIIB, MNMIIC) no centro do tumor, zona de invasão e tecido epitelial não neoplásico adjacente ao tumor, relacionando a expressão e localização dessas proteínas com os dados descritos bem como evolução dos pacientes após 5 anos de acompanhamento. De acordo com os resultados sugere-se que a MNMIIB expressa no EA possa indicar o potencial de metástase regional do CEC e a MNMIIC presente na zona de invasão tumoral (ZI) seja um fator predictor de prognóstico ruim da doença. Sendo assim, é possível propor que a avaliação de imunorreatividade da MNMIIB no EA e MNMIIC na ZI seja utilizada na análise das peças operatórias, como complemento à análise morfológica de rotina. / Squamous cell carcinoma (SCC) of the head and neck is a malignant neoplasm of poor prognosis and low survival rate. Understand the biological processes involved in carcinogenesis can be extremely important for the development of new treatment technologies and improved prognosis in patients affected by the disease. The major cause of clinical failure in terms of therapy and prognosis in cancer patients is the development of tissue invasion and metastatic potential. Cell migration is essential for tumor progression and the cells have molecular motors especially formed from non-muscular myosin II family (NMMII). Encoded by different genes, there are three known isoforms in mammalian cells (NMMIIA, NMMIIB, NMMIIC). The NMMIIs are involved in cellular functions such as migration, adhesion, and cytokinesis. As the understanding of migration, cell adhesion and cytokinesis key factors in tumor progression, and that the tissue invasion and metastatic potential for development are essential in defining the prognosis of patients, the objective of this study was to describe the profile and exposure to risk factors such as alcohol and tobacco of patients diagnosed with head and neck SCC, histological grading, tumor clinical parameters (TNM), pattern of expression of isoforms NMMII (NMMIIA, NMMIIB, NMMIIC) in the center of the tumor (CT), tumor invasion zone area and not neoplastic adjacent to the tumor (AE), relating the expression and localization of these proteins with the data described and outcome of patients after 5 years of follow-up. According to the results it is suggested that the NMMIIB expressed in AE may indicate the potential regional metastasis of SCC and NMMIIC present in the tumor invasion zone (IZ) is a predictor factor of poor prognosis of the disease. Therefore, it is possible to propose that immunoreactivity assessment of NMMIIB in EA and NMMIIC in IZ could be used in the analysis of operative parts, as a complement to routine morphological analysis.