En esta tesis se realiza un estudio comparativo y analítico, que ordena la población del estudio en dos grupos A y B, con el objetivo de la descripción, valoración, análisis, evaluación y comprobación de los datosespecíficos de la valoración de acertada identificación, desarrollo y precisión del método clínico y del método de imágenes de RMN (en adición del método clínico) para realizar el diagnóstico de una posible lesión meniscal (interna y/o externa) aislada o acompañada de otras lesiones articulares de la rodilla. Se contrasta ambos grupos A y B, según el modelo estadístico elaborado de casos y controles, valorando retrospectivamente el conjunto de datos de la comparación entre ambos grupos, en sus contenidos, y en específico para evaluar estadísticamente la importancia, efectividad, utilidad, aporte y precisión de los métodos diagnósticos referentes utilizados, contrastando los grupos A y B, y tomando la artroscopia como método estándar para el total de la población de esta Investigación. El propósito de tener un diagnóstico de las lesiones meniscales de la rodilla que sea acertado, seguro y de gran precisión facilita el tratamiento apropiado, aplicado posteriormente al diagnóstico correcto, y efectivamente la buena recuperación e incorporación a la vida activa y laboral. Se tratará en esta tesis de evaluar el valor real de los criterios diagnósticos específicos realizados para el diagnóstico de la lesión meniscal (con o sin otras lesiones articulares de la rodilla) y la determinación de las características del aporte conjunto y específico de los métodos aplicados para obtener sus funciones reales e indicaciones diagnósticas precisas en el diagnóstico meniscal. Respecto a la población del grupo A, se ha realizado el diagnóstico meniscal por ambos métodos: clínico y por imágenes de RMN. En el grupo de control (grupo B) se ha realizado el diagnóstico únicamente por los criterios del método clínico. Se toma la artroscopia como método estándar en la comparación creada entre el grupo A y el grupo B (artroscopia diagnóstica y/o terapéutica). De modo específico, se comprueba el valor y la importancia del método clínico, el cual ha sido elaborado por los criterios clínicos comprendidos por la historia y exploración clínica (interrogatorio clínico, síntomas, signos y pruebas clínicas), con o sin el método RMN; e identificar las utilidades e indicaciones precisas del método tecnológico de RMN junto al método clínico para establecer un diagnóstico sólido y seguro, y los beneficios alcanzados con esta indicación para la futura terapia meniscal y para establecer las debidas y precisas indicaciones, diagnósticas y/o terapéuticas, realizados por el método de la artroscopia de la rodilla.Se evidencia igualmente, de forma clasificada y específica, la capacidad y eficacia del método tecnológico (imágenes de RMN) en adición al método clínico para identificar, diagnosticar y precisar las otras alteraciones articulares de la rodilla que acompañan a las lesiones meniscales (internas y/o externas), tal como lesiones del cartílago articular, ligamentosas, capsulares, sinoviales, degenerativas, congénitas, etc.

Clinical and epidemiological studies support a strong association between chronic inflammation and cancer. Inflammatory related cytokines, such as IL-1£\, IL-1RN, IL-1£], IL-4, IL-6, IL-8, IL-10, TNF-£\ and TGF£]-1, might play important role in carcinogenesis of oral squamous cell carcinoma (OSCC). Two case-control studies were carried out to evaluate the association of 16 various polymorphisms of 9 inflammatory-related genes with the risk for OSCC and the risk for betel quid (BQ)-related oral precancer lesions (OPL) and BQ-related OSCC. Then the association between various IL-1B C-511T/T-31C haplotypes with plasma levels of IL-1£] was evaluated. One case-contol study included 363 OSCC case patients and 487 healthy controls as well as the other case-control study included 227 BQ-related OSCC cases, 116 BQ-related OPL patients and 209 BQ-related controls. All subjects were recruited and genotyped by use of the PCR-RFLP techniques or TaqMan real-time PCR method from November 2003 and May 2007 at Kaohsiung Veterans General Hospital. Then, 9 OSCC case patients, 9 OPL patients, and 9 controls were selected and matched on sex, age as well as the quantity of BQ-chewing, alcohol drinking, and cigarette smoking for evaluation of plasma levels of IL-1£] by use of ELISA. In the single locus analysis, the variant genotype of RP1RP2 or RP2RP2 (VS. RP1RP1) of IL-4 intron 3 VNTR (AOR = 0.67, 95% CI = 0.45-0.99; AOR = 0.65, 95% CI = 0.45-0.95), TA or AA (VS. TT) genotype of IL-8 T-251A (AOR = 1.55, 95% CI = 1.05-2.30; AOR = 2.50, 95% CI = 1.46-4.27), TT (VS. CC) genotype of IL-8 C+781T (AOR = 2.01; 95% CI = 1.11-3.63), and GA combined with AA (VS. GG) genotype of TNFA G-308A (AOR = 0.40; 95% CI = 0.25-0.66) were associated with risk of OSCC, as compare with those genotypes of healthy controls. However, CC (VS. TT) genotype of IL-10 T-819C (AOR = 0.24, 95% CI = 0.08-0.74) and CC (VS. AA) genotype of IL-10 A-592C (AOR = 0.25, 95% CI = 0.08-0.79) were significantly associated with reduced risk of BQ-related OPL, as compared with those genotypes of BQ controls. In addition, the variant genotype of 2/2 or 1/2 (VS. 1/1) of IL-1RN intron2 VNTR (AOR = 0.11, 95% CI = 0.01-0.97; AOR = 0.48, 95% CI = 0.27-0.87), TC (VS TT) genotype of IL-1B T-31C (AOR = 1.82, 95% CI = 1.14-2.92), AA (VS. TT) genotype of IL-8 T-251A (AOR = 1.92, 95% CI = 1.01-3.66), GG (VS. TT) genotype of IL-8 T+396G (AOR = 2.18; 95% CI = 1.12-4.21), and GA combined with AA (VS. GG) genotype of TNFA G-308A (AOR = 0.46, 95% CI = 0.27-0.79) were significantly related with risk of BQ-related OSCC, as compared with BQ controls. Moreover, CC (VS. TT) genotype of IL-10 T-819C (AOR = 3.33, 95% CI = 1.07-10.42) was associated with increased risk of BQ-related OSCC, as compared with those genotypes of BQ-related OPL. In the haplotype analysis, -590C/RP2 (VS. -590T/RP1) haplotype of IL-4 (AOR = 0.69; 95% CI = 0.49-0.98) and -251A/+781T (VS. -251T/+781C) haplotype of IL-8 (AOR = 1.57, 95% CI = 1.19-2.06) were related with risk of OSCC, as compared with those haplotypes of healthy controls. However, -511C/-31C (VS. -511C/-31T) haplotype of IL-1B (AOR = 0.00, 95% CI = 0.00-0.01) and -1082A/-819C/-592C (VS. -1082A/-819T/-592A) haplotype of IL-10 (AOR = 0.66, 95% CI = 0.44-0.98) were strongly associated with reduced risk of BQ-related OPL, as compared with those genotypes BQ controls. In addition, -889C/2/-511C/-31T or -889T/1/-511C/-31T or -889T/1/-511T/-31C (VS. -889C/1/-511C/-31T) haplotypes of IL-1 family genes (AOR = 0.47, 95% CI = 0.26-0.87; AOR = 0.31, 95% CI = 0.13-0.73; AOR = 3.26; 95% CI = 1.34-7.93) were associated with risk of BQ-related OSCC, as compared with those genotypes of BQ controls. On the contrary, -511T/-31T (VS. -511C/-31T) haplotype of IL-1B (AOR = 0.34, 95% CI = 0.12-0.97) and -889T/1/-511C/-31T (VS. -889C/1/-511C/-31T) haplotype of IL-1 family genes (AOR = 0.27, 95% CI = 0.10-0.71) were associated with reduced risk of BQ-related OSCC, as compared with those haplotypes of BQ-related OPL. Finally, in the stratification analysis, the combined effects of three genes (IL-8 T-251A, IL-4 intron 3 VNTR and TNFA G-308A) had a significantly increased risk of OSCC among male, older group (¡Ö50 years old), Fukienece combined with Aborigine population, never-BQ chewers, never as well as heavy smokers, or light and heavy drinkers, compared with healthy controls. The results suggested that gene-environment combined effect were associated with the risk of OSCC. In ELISA assay, plasma IL-1£] levels in BQ-related OSCC and OPL were found significantly higher than those in haplotypes for IL-1B -511T/-31C and IL-1B -511T/-31T compared with the combined effects of IL-1B -511C/-31C and IL-1B -511C/-31T. In conclusion, polymorphisms of IL-1RN, IL-4 and TNFA were associated with the decreased risk of OSCC or BQ-related OPL, but IL-8 was with increased risk of OSCC or BQ-related OPL. Furthermore, polymorphisms of IL-1B and IL-10 had contrary effect between BQ-related OSCC and OPL. Additionally, plasma levels of IL-1£] was correlated with various IL-1B C-511T/T-31C haplotypes but not with correlated with the status of disease.

Motor skill learning underlies much of what we do, be it hitting a tennis serve, playing the piano, or simply brushing our teeth. Yet despite its importance, little is known about the neural circuits that implement the learning process or how the motor program is represented in the brain. Here I explore the role of motor cortex through lesion studies in rats trained on a motor skill. First, I interrogate whether motor cortex is necessary for the production of a complex motor sequence by training animals to produce temporally precise self-initiated movement sequences on a lever-pressing task. The movement sequences that emerged over months of training were remarkably complex, yet very precise. This motor skill, once mastered, survives large bilateral motor cortex lesions, suggesting that motor cortex is not required for generating movement sequences after consolidation. Next, I explored the role of motor cortex in motor skills that require dexterous manipulations. Animals trained to make constrained spatially precise movements using a joystick were impaired after motor cortex lesions. The role of motor cortex thus depends on the nature of the movements involved but not on the sequencing of movements. Third, I explored the function of motor cortex in sensorimotor transformations by training animals on the same lever-pressing task but with external cues instead of self-initiated movement. Surprisingly, these animals were also not impaired after lesions, suggesting that the method of learning the motor sequence has no consequence once the motor sequences are consolidated. Lastly, I explored the role of motor cortex in learning motor skills. Animals that were lesioned after being exposed to the lever-pressing task could learn to adjust the timing of their movements, indicating that motor cortex is not required for adapting a previously-acquired motor sequence. Lesions of motor cortex prior to any training, however, severely disrupted learning. Even with extended training, animals were unable to fully master the task, demonstrating that motor cortex is necessary for the acquisition of new motor skills even when it is not required for their execution.

No description available.

The presence of distributed micro-calcifications can be an indicator of early breast cancer. On the mammogram, they appear as bright smooth particles superimposed on the normal breast image background. Radiologists determine the occurrence of this lesion by detecting the individual micro-calcifications and then examining their distribution within the breast tissue. Due to the visual complexity of the mammogram, the detection sensitivity is usually less than 100%. The digital environment has the potential to increase the radiologist's accuracy. We have developed a computer aided detection (CAD) scheme that can identify clinically indicative clusters of micro-calcifications. The CAD algorithm emulates some aspects of the radiologists' approach by using contrast texture energy segmentation and morphological distribution analysis. On a local database of 61 mammograms digitised at 100μm with 8 bits intensity resolution, the CAD returns: a) 85% sensitivity (91% for malignant lesions and 78% for those that are benign), b) 0.33 false positive clusters (FPC) per image and c) 92% specificity. Therefore, the output from the CAD is shown to compare favourably with the performance of an expert radiologist. It also compares favourably with other CAD techniques, exceeding many algorithms which employ a higher level of mathematical complexity. The scheme is tested on an international database provided by the Mammographic Image Analysis Society. In this case it returns a) 96.4% sensitivity (100% for malignant lesions and 92% for those that are benign) b) 2.35 FPC rate per image and c) 33% specificity. The higher FPC rate is attributed to the different acquisition and production of the digital mammograms. It is concluded that this can be reduced by employing a shape analysis procedure to the CAD's final output. It is shown that the image processing principles we have implemented are generally successful on databases which are produced at other centres under different technical conditions.

In rural Bangladesh people drink water from an estimated 10-11 million tube wells, many with arsenic concentrations well above the national standard of 50µg/L. Characteristic skin lesions and more serious health effects are probable. The research reported here was designed to determine the relation between arsenic concentration and skin lesions on hands and feet controlling for education, use of tube well water, protein consumption and body mass index (BMI). The investigation included a well survey, a prevalence survey and a nested case-referent analysis. Studies were conducted in two villages (population 11670) in northern Bangladesh. In the well survey 1509 wells in use were identified and measurements of arsenic concentration made in 1422 (94%). Three estimates were made for each well, which yielded correlation among repeats = 0.93. The overall median was 47mg/L and the highest recorded 1760 mg/L. Paramedics examined soles and palms of 11087 individuals for skin lesions and identified 168 cases (1.5%). In the third phase, cases (over 16 years) were matched by age, gender and village to referents (target of 3) without skin lesions. Cases and referents were interviewed about protein in diet, use of well water, education and residential history. Conditional logistic regression was used to assess the effects of arsenic concentration, controlling for confounders. Subjects with lesions had a higher median concentration (250µg/L) than those without (47µg/L). Prevalence increased with both age and arsenic concentration, reaching 26.7% in those over 50 years of age and >500 µg/L. Of the 160 cases (≥16 years) 137 were interviewed, 127 with arsenic concentration measured in well water, together with their 504 referents. Cases were somewhat more likely to have lived in the villages throughout their lives and less likely to report using tube well water for cooking. The final model confirmed the high risk of lesions associated with arsenic concentrations. Using ≤50µg/L for comparison, an odds ratio of 15.2 (95%CI 7.2-32.2) was observed for those using tube wells with concentrations >500 µg/L, adjusting for use of tube well water in cooking and lifetime residence in the villages. The results from this research provide continuing support for the use of 50µg/L as a useful national standard. While the enforcement of this standard has immediate value, it cannot be considered final without comparable information on more serious health risks.

No description available.

It is common for pigs to engage in physical aggression when mixed into new social groups, in order to establish dominance relationships. Phenotyping aggression is time consuming, however skin lesions resulting from physical aggression are quick to record, are genetically correlated with aggressive behavioural traits, and have low to moderate heritability (0.19 to 0.43). Reducing aggression via selection on skin lesion traits would provide a socially acceptable, long-term solution to the problem. Barriers to implementing selection against skin lesions lie in the lack of understanding regarding the underlying genetic basis of aggression, and its relationship with other behaviour and production traits. This thesis has focused on dissecting the phenotypic and genetic relationship between skin lesions recorded 24 hours after mixing (SL24h), and either 3 or 5 weeks later (SL3wk/SL5wk, respectively), with aggression performed at mixing, and several production traits. Chapter 2 provided evidence of a potential trade-off between involvement in aggression upon first mixing, and receipt of aggressive attacks several weeks after mixing. In particular, animals that avoid aggression at mixing had the highest fresh skin lesion numbers at 3 weeks. This suggests that reciprocal fighting at mixing may be beneficial for long-term group social stability. It also suggests that it may be possible to phenotype the least aggressive individuals in a group using SL3wk. In Chapter 3, I quantified the magnitude of reduction in complex aggressive behavioural traits when using SL24h or SL3wk as selection criteria, to identify the optimum skin lesion trait for selection purposes. The results of Chapter 3 provided evidence that selection against anterior SL24h would result in the greatest genetic and phenotypic reduction in aggressive behaviour recorded at mixing. Although there is evidence that selection for increased SL3wk would reduce aggression at mixing, current understanding of aggressive behaviour under stable group conditions is insufficient to recommend using this trait for selection purposes. Chapter 4, presented genetic associations between skin lesion traits as a measure of short- and long-term aggression, and commonly used commercial performance measures: growth, feed intake, feed efficiency, and carcass traits. The results suggested that, genetically, animals that receive many lesions show improved performance compared to those with few lesions, except for anterior SL24h, which have been shown to be genetically positively correlated with the initiation of nonreciprocal attacks. The aim of Chapter 5, was to determine whether skin lesion traits are phenotypically or genetically associated with behavioural measures of fearfulness. As found in Chapter 4, there was some evidence of an association between SL5wk and the traits, however this was not the case for anterior SL24h. For the 6th and final Chapter, we used skin lesion data from 1,840 pigs to perform genome wide association studies (GWAS), which detected a single SNP significantly associated with SL5wk on a genome wide level, as well as several SNPs associated with both SL24h and SL5wk on a chromosome wide level.

Orientador: Antonio José Maria / Resumo: Justificativa: as lesões da mucosa traqueal em contato com o balonete do tubo traqueal são proporcionais à pressão exercida pelo balonete e ao tempo de exposição. Objetivo: estudar as eventuais lesões da mucosa do segmento traqueal em contato com o balonete do tubo traqueal insuflado com volume de ar suficiente para se obter a pressão de "selo" para impedir vazamento durante ventilação artificial, ou com a pressão "crítica" de 25 cm H2O. Método: dezesseis cães foram submetidos à anestesia venosa com pentobarbital sódico e ventilação com fluxo total de gases frescos de 2 L.min-1. Os cães foram distribuídos aleatoriamente em dois grupos de acordo com a pressão no balonete de grande volume do tubo traqueal (Portex Blue-Line, Inglaterra): G1 (n=8) balonete insuflado até a obtenção da pressão mínima de "selo" necessária para impedir vazamento de ar durante a respiração artificial; G2 (n=8) balonete insuflado até atingir a pressão de 25 cm de H20. A medida da pressão do balonete foi realizada por meio de manômetro digital (Mallinckrodt, EUA) no início do experimento (controle) e após 60, 120 e 180 minutos. Após osacrifício dos cães, foram feitas biópsias nas áreas traqueais adjacente ao tubo traqueal para análise à microscopia óptica (MO) e microscopia eletrônica de varredura (MEV). Resultados: à MO, evidenciaram-se mínimas alterações em ambos os grupos, mais significantemente em G1, em duas áreas da parede anterior da traquéia: uma em contato com o balonete (BB1) e outra abaixo do tubo traqueal (BP1) (p=0,002). À MEV as alterações não foram significantemente diferente nos grupos (p>0,30), mas ocorreram lesões mais intensas nas áreas de contato com o balonete nos dois grupos (p<0,05). Conclusões: no cão, nas condições experimentais empregadas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: The lesions of the tracheal mucosa in contact with the endotracheal tube cuff are proportionally related to the intracuff pressure and to the time of exposition. Objective: the aim of this work was to study the development lesions of tracheal mucosa in contact with the endotracheal tube cuff inflated to reach the "sealing" pressure in order to avoid leaking during the artificial ventilation or with the "peak" inflation pressure of 25 cm H2O. Methods: sixteen dogs were submitted to intravenous anesthesia with pentobarbital sodium and ventilation with total flow of fresh gases of 2 L.min-1. The dogs were randomly distribuited into two experimental groups according to the pressure in the high volume cuff of the endotracheal tube (Portex Blue Line, Inglaterra): G1 (n=8) the cuff was inflated in order to reach the sealing minimum pressure to avoid air leaking during the artificial respiration; G2 (n=8) the cuff was inflated to reach the pressure of 25 cm H2O. The intracuff pressure was measured with a digital manometer (Mallinckrodt, EUA) at the beginning of the experiment (control) and after 60, 120 and 180 minutes. The animals were sacrificied and biopsies were perfomed from the areas of the trachea adjacent the endotracheal tube to be analysed by light microscopy (LM) and scanning electronic microscopy (SEM). Results: The light microscopy showed mild and similar alterations in both groups. However G1 revealed alterations most frequently in two different areas of trachea anterior wall: one lesion in direct contact with the cuff (BB1) and the other lesion just below the tracheal tube (BP1) (p=0.002). The scanning electronic microscopy also showed similar alterations in both groups (P>0.30), with more. Conclusions: In the dog, considering the experimental conditions used... (Complete abstract, click electronic address below) / Doutor

Orientador: Julio Defaveri / Resumo: A paracoccidioidomicose (Pbmicose) é micose sistêmica na qual complexos eventos inflamatórios e imunológicos são desencadeados pela interação fungo-hospedeiro, resultando em duas características importantes da doença: freqüente instalação de distúrbios imunorregulatórios e reação inflamatória granulomatosa. Este trabalho teve por objetivo estudar em pacientes portadores da forma crônica multifocal da Pbmicose, na fase pré-tratamento, as características da resposta granulomatosa em lesões de pele e mucosa, considerando suas populações celulares e a presença in situ de citocinas de padrão Th1 e Th2. Estes achados foram correlacionados com a gravidade clínica, níveis de competência imunológica humoral e celular e níveis séricos dessas mesmas citocinas. Foram estudados 27 pacientes com gravidade clínica moderada (13 pacientes), moderada/grave (8 pacientes), grave (5 pacientes) e não avaliada (1 paciente). As biópsias foram realizadas por punch de lesões de pele ou mucosa. Os soros foram separados de sangue obtido por punção venosa, e o teste cutâneo realizado pela paracoccidioidina. Nas biópsias foram analisados o número e padrão de distribuição de neutrófilos, eosinófilos, células gigantes, plasmócitos, linfócitos T CD3+ e CD8+, linfócitos B e células NK (estes três últimos caracterizados pela imuno-histoquímica), contagem de fungos e a detecção imuno-histoquímica de IL-4, IFN- , IL-10, TNF- e TGF- . No soro dos pacientes foram realizadas dosagens de IL-2, IL-4, IL-10 e TGF- e de anticorpos específicos anti-Pb por ensaio imunoenzimático (ELISA)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Paracoccidioidomycosis (Pbmycosis) is a systemic mycosis in which a complex inflammatory and immunological events are unchained by the interaction of the fungus (Pb) with the host tissues, resulting in two important characteristics of the disease: frequent immunoregulatory disturbances and a granulomatous inflammation. The aim of this work was to study in patients with the chronic multifocal form of Pbmycosis, before treatment, the characteristics of the granulomatous response in skin and mucosal lesions, considering the cellular populations and the presence in situ of Th1 and Th2 cytokines patterns. These results were correlated with the clinical severity, the levels of humoral and cellular immune competence and serum levels of those cytokines. Twenty seven patients were studied, distributed accordingly to clinical severity: moderate (13 patients), moderate/severe (8 patients), severe (5 patients), and not evaluated (1 patient). Punch biopsies were collected from skin or mucosal lesions, the serum obtained from venous blood samples to measured antibodies levels, and the skin test accomplished by the paracoccidioidin. In biopsies the following parameters were evaluated: the number and distribution pattern of neutrophils, eosinophils, giant cells, plasma cells, T CD3+ and CD8+ cells, B cells and NK cells (the last three characterized by immunohistochemistry), number of fungi, and detection of IL-4, IFN- , IL-10, TNF- and TGF- by immunohistochemistry. It was also measured the serum levels of IL-2, IL-4, IL-10 and TGF- and the level of specific antibodies anti-Pb by ELISA test. Specific granulomatous lesions, composed with epithelioid, well organized granuloma together with epithelioid loose, ill organized granuloma were observed in the same lesion of the dermis and submucosa. Neutrophils... (Complete abstract, click electronic address below) / Doutor