Clinical wisdom suggests that adults with histories of childhood trauma will have difficulty engaging in psychotherapy. I examined the relationship between early childhood trauma and treatment response in the form of rate of symptom decline among a group of 202 adults recruited into the longitudinal Austen Riggs Center Follow-Along Study. Participants were recruited at admission to the hospital and provided extensive demographic and clinical data at baseline, including retrospective recall of childhood traumatic experiences using the Traumatic Antecedents Interview (TAI) and narrative responses to the Relationship Anecdote Paradigm (RAP) used to generate ratings on the Social Cognition and Object Relations Scale (SCORS). Participant symptoms were assessed at baseline and again every six to eight months for up to four years using the Symptom Checklist-90-Revised (SCL-90-R). Hierarchical Linear Modeling (HLM) was used to perform growth curve modeling of the symptom change data, which demonstrated an overall linear rate of decline and significant unexplained variability. The hypothesis that degree of childhood trauma would predict rates of symptom change failed to receive support, as did other related hypotheses. Only participant age predicted differences in rates of symptom decline, with younger participants' symptoms declining more rapidly than those of older participants. The findings indicate the following: (1) symptom severity tends to decline linearly after hospital admission, (2) individual rates of symptom change vary considerably, and (3) rates of symptom decline may slow as people age. Implications for clinical research and practice are discussed.

Pre-clinical study of cancer often involves imaging different aspects of a tumor, ranging from visualizing sub-cellular detail to imaging of the tumor anatomy. Multimodal imaging seeks to combine imaging techniques with complementary strengths and use them to provide a more complete picture of the disease. In this dissertation work, the development of various optical, nuclear and magnetic resonance imaging (MRI) techniques applicable to the study of cancer xenografts in murine window chamber models was carried out. Two types of window chamber models were used in this work: the dorsal skinfold WC (DSFWC) model and the mammary WC (MWC) model. The MWC was specifically used to study breast cancer xenografts. In this work, optical pH imaging with a pH-sensitive fluorescent agent was used to evaluate methods to achieve tumor-specific pH modulation. Temporary tumor acidification was performed by administration of an agent that consists of glucose and meta-iodobenzylguanidine. On the other hand, re-normalization of pHₑ in acidic tumor tissue was achieved by administration of buffer solutions, such as sodium bicarbonate. A broadband reflectance spectral imaging system was developed to perform in vivo imaging of oxygen saturation in the MWC murine model. The imaging system was used to study tissue oxygenation changes in animals that receive chemotherapy. Preliminary results were obtained to evaluate the utility of the MWC murine model in imaging the spatiotemporal changes in oxygen saturation (SaO₂) as an early biomarker of response to neo-adjuvant chemotherapy. To study metabolic activity, nuclear imaging of radiolabeled fluorodeoxyglucose (18F-FDG) was carried out using a beta-imager, as well as a pre-clinical PET system. The 2D nuclear imaging capability of the beta-imager was cross-validated with the 3D PET imaging system. Anatomical and functional MRI was performed on the MWC murine model. Anatomical MRI was used to study tumor growth rates, which aid in the identification of animals that responded to chemotherapy. In addition, diffusion-weighted (DW) MRI, dynamic-contrast-enhancement (DCE) MRI, and perfusion MRI were performed to study various functional aspects of the tumor xenografts. Lastly, work was done to incorporate patient derived xenograft (PDX) tumors into the MWC murine model. As opposed to xenografts grown from cultured cancer cells, PDX tumors better recapitulate characteristics of human tumors. This new cancer model is aimed at improving the translational power of pre-clinical studies employing window chamber models.

O transtorno obsessivo-compulsivo (TOC) possui freqüentemente curso crônico, incapacitando cerca de 10% dos seus portadores. Os sintomas interferem de forma acentuada na vida do paciente, alterando suas rotinas e causando incompreensão dos familiares e daqueles que convivem com ele. A terapia cognitivo-comportamental em grupo (TCCG) é um tratamento eficaz, reduzindo os sintomas do TOC em mais de 70% dos portadores, sendo que ao redor de 27% obtêm remissão completa dos sintomas. Entretanto, cerca de 30% não obtêm nenhuma melhora. Conhecer as razões pelas quais esses pacientes não melhoram e identificar os fatores preditores associados ao aproveitamento ou não da terapia poderia auxiliar em uma melhor compreensão do TOC, numa melhor indicação do tratamento e no desenvolvimento de estratégias que incrementem sua eficácia. O presente estudo foi realizado com 181 pacientes com TOC, que cumpriram um programa de TCCG de 12 sessões semanais de 2 horas, entre outubro de 1999 e dezembro de 2006, no Programa de Transtornos de Ansiedade (PROTAN) do Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS) e tinha como objetivo verificar, em pacientes portadores de TOC, a existência de fatores preditores da resposta à TCCG.Os pacientes foram avaliados antes, durante e ao final do tratamento com os seguintes instrumentos: Y-BOCS, Y-BOCS chek-list, CGI, WHOQOL-BREF. Foi utilizada uma entrevista clínica estruturada com a finalidade de colher dados sobre os sintomas do paciente, histórico da doença, tratamentos anteriores e estabelecimento do diagnóstico do TOC de acordo com o DSM-IV-TR. Também foram coletados dados demográficos, socioeconômicos, status ocupacional, uso de medicação e critérios deinclusão na pesquisa. A entrevista foi complementada pelo MINI (International Neuropsychiatric Interview) para verificar a presença de comorbidades. Considerou-se como “resposta” a redução no mínimo de 35% nos escores da Y-BOCS e uma pontuação na CGI “normal” ou “limítrofe para doença” do pós para o pré-tratamento. O estudo pretende verificar se as seguintes variáveis: sexo, idade do paciente no início do tratamento, tempo de duração da doença, idade de início da doença, situação conjugal, nível de instrução, situação ocupacional, tipo de início da doença, curso, intensidade dos sintomas do TOC no início do tratamento, juízo crítico, história familiar, tipos de sintomas, uso de medicação específica para o TOC concomitante à TCCG estão associadas ou não com a resposta ao tratamento. Para avaliar a associação entre as variáveis categóricas à resposta ao tratamento, foi utilizado o teste qui-quadrado de Pearson. Nas variáveis dicotômicas foi aplicada a correção de Yates. Para avaliar as variáveis quantitativas em relação às categorias de resposta ao tratamento, foi utilizado o teste t de Student para amostras independentes. As variáveis que obtiveram um nível descritivo amostral (valor p) menor do que 0,25 foram inseridas no modelo de regressão logística múltipla.Fatores associados com uma melhor resposta à TCCG: sexo feminino (p=0,074); melhor juízo crítico acerca dos sintomas da doença (p=0,017); melhor qualidade de vida antes do início do tratamento: domínio físico (p=0,039), domínio psicológico (p<0,001), domínio ambiental (p=0,038), domínio social (p=0,053). Fatores associados com piores resultados: maior gravidade global da doença no início do tratamento, avaliada pela CGI (p=0,007); maior número de comorbidades associadas ao TOC (p=0,063); presença de fobia social (p=0,044) e distimia (p=0,072); presença de compulsão de repetição (p=0,104).Numa segunda etapa da análise estatística, incluiu-se no modelo todas as variáveis que na primeira fase haviam apresentado associação com os resultados. As variáveis que na análise de regressão logística múltipla permaneceram associadas significativamente foram: sexo feminino (ORAjustado=2,58; p=0,021); domínio psicológico da WHOQOLBREF (ORAjustado=1,05; p=0,011); juízo crítico (ORAjustado=2,67; p=0,042) e CGI-gravidade antes do inicio da terapia (ORAjustado=0,62; p=0,045). Embora alguns fatores relacionados com a resposta ao tratamento tenham sido identificados, poder prever quais os pacientes irão aproveitar a terapia e quais não irão se beneficiar é uma questão em aberto e está longe de ser esclarecida. As razões para essas dificuldades podem estar relacionadas à heterogeneidade do TOC e das amostras utilizadas nos diferentes estudos, além da falta de padronização das técnicas psicoterápicas utilizadas. Por fim, é possível que fatores não-específicos relacionados com a pessoa do terapeuta, com a qualidade da relação terapêutica, além da motivação e capacidade de tolerar frustração por parte do paciente possam exercer um papel importante que não tem sido avaliado pelas pesquisas. / Obsessive-compulsive disorder (OCD) frequently is a chronic disorder that incapacitates about 10% of patients. Symptoms severety affect the life of patients, change their routines and cause misunderstandings with family and all those that have contact with the patient. Group cognitive-behavioral therapy (GCBT) in 12 two-hour weekly sessions is an efficient treatment that reduces OCD symptoms in over 70% of the patients and results in complete remission of symptoms in 27%. However, about 30% of the patients do not show any improvement. The knowledge of reasons why these patients do not improve and the identification of factors associated with these different therapy outcomes may help to understand OCD better, and may inform treatment indications and the development of strategies to increase its efficacy. This study included 181 patients with OCD treated with 12 session of GCBT from October 1991 to December 2006 at the Anxiety Disorders Program (Programa dos Transtornos de Ansiedade – PROTAN) of Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. The purpose of this study was to investigate predictors of response to GCBT.The following instruments were used to evaluate patients before and at the end of the treatment: Y-BOCS, Y-BOCS checklist, CGI, WHOQOL-BREF. Evaluation was conducted by means of a structured clinical interview to collect data about the patient’s symptoms, disease history, previous treatments, and OCD diagnosis according to DSM-IVTR (APA, 2002). Demographic and socioeconomic data, occupational status, use of medication and criteria for inclusion in the study were also recorded. The interview wascomplemented with the MINI (International Neuropsychiatric Interview) to investigate comorbidities. Response criteria were: >35% reduction in Y-BOCS scores and normal or borderline CGI scores at post-treatment evaluation. The study investigated the possible association of the following variables with response to treatment: sex, age at beginning of treatment, disease duration, age at onset, marital status, education, occupation, type of disease onset, disease course, intensity of OCD symptoms at beginning of treatment, insight, family history, types of symptoms, and use of antiobsessional medications during GCBT. The Pearson chi-square test was used to evaluate the association between categorical variables and response to treatment. Yates correction was performed for dichotomous variables. The Student t test for independent samples was used to evaluate quantitative variables in relation to categories of response to treatment. Variables that achieved a p value lower than 0.25 were included in the initial logistic regression model, which evaluated the predictors of response to treatment and also controlled for possible confounding variables. The following factors showed associations with response to GCBT: women had greater odds of responding to treatment (p=0.074); better insight into disease symptoms was associated with better results (p=0.017); better quality of life before the beginning of treatment was also associated with better results (physical domain: p=0.039; psychological domain: p<0.001; environmental domain: p=0.038; social domain: p=0.053); patients with greater global severity of disease according to CGI had worse results (p=0.007); a greater number of associated comorbidities (p=0.063), social phobia (p=0.044) and dysthymia (p=0.072) were associated with poorer results; repeating compulsion was also associated with lower odds of responding to treatment (p=0.104).In the second stage of statistical analysis, all variables associated with results in the first analysis were included in the multivariate model, and the variables that retained significance were: female sex (ORAdjusted=2.58; p=0.021); WHOQOL-BREF psychological domain (ORAdjusted=1.05; p=0.011); insight (ORAdjusted=2.67; p=0.042) and CGI-severity before GCBT (ORAdjusted=0.62; p=0.045). Although we identified some factors associated with response to treatment, predicting which patients will benefit from therapy and which will not is still an open question. The reasons for such different outcomes may be associated with the heterogeneity of OCD and of the samples used in different studies, as well as with the lack of standardization of the psychotherapeutic techniques used. Finally, unspecific factors not associated with the person of the therapist, the quality of the therapeutic relationship, and the patient’s motivation and tolerance to frustration may play an important role that remains to be evaluated.

O transtorno obsessivo-compulsivo (TOC) possui freqüentemente curso crônico, incapacitando cerca de 10% dos seus portadores. Os sintomas interferem de forma acentuada na vida do paciente, alterando suas rotinas e causando incompreensão dos familiares e daqueles que convivem com ele. A terapia cognitivo-comportamental em grupo (TCCG) é um tratamento eficaz, reduzindo os sintomas do TOC em mais de 70% dos portadores, sendo que ao redor de 27% obtêm remissão completa dos sintomas. Entretanto, cerca de 30% não obtêm nenhuma melhora. Conhecer as razões pelas quais esses pacientes não melhoram e identificar os fatores preditores associados ao aproveitamento ou não da terapia poderia auxiliar em uma melhor compreensão do TOC, numa melhor indicação do tratamento e no desenvolvimento de estratégias que incrementem sua eficácia. O presente estudo foi realizado com 181 pacientes com TOC, que cumpriram um programa de TCCG de 12 sessões semanais de 2 horas, entre outubro de 1999 e dezembro de 2006, no Programa de Transtornos de Ansiedade (PROTAN) do Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS) e tinha como objetivo verificar, em pacientes portadores de TOC, a existência de fatores preditores da resposta à TCCG.Os pacientes foram avaliados antes, durante e ao final do tratamento com os seguintes instrumentos: Y-BOCS, Y-BOCS chek-list, CGI, WHOQOL-BREF. Foi utilizada uma entrevista clínica estruturada com a finalidade de colher dados sobre os sintomas do paciente, histórico da doença, tratamentos anteriores e estabelecimento do diagnóstico do TOC de acordo com o DSM-IV-TR. Também foram coletados dados demográficos, socioeconômicos, status ocupacional, uso de medicação e critérios deinclusão na pesquisa. A entrevista foi complementada pelo MINI (International Neuropsychiatric Interview) para verificar a presença de comorbidades. Considerou-se como “resposta” a redução no mínimo de 35% nos escores da Y-BOCS e uma pontuação na CGI “normal” ou “limítrofe para doença” do pós para o pré-tratamento. O estudo pretende verificar se as seguintes variáveis: sexo, idade do paciente no início do tratamento, tempo de duração da doença, idade de início da doença, situação conjugal, nível de instrução, situação ocupacional, tipo de início da doença, curso, intensidade dos sintomas do TOC no início do tratamento, juízo crítico, história familiar, tipos de sintomas, uso de medicação específica para o TOC concomitante à TCCG estão associadas ou não com a resposta ao tratamento. Para avaliar a associação entre as variáveis categóricas à resposta ao tratamento, foi utilizado o teste qui-quadrado de Pearson. Nas variáveis dicotômicas foi aplicada a correção de Yates. Para avaliar as variáveis quantitativas em relação às categorias de resposta ao tratamento, foi utilizado o teste t de Student para amostras independentes. As variáveis que obtiveram um nível descritivo amostral (valor p) menor do que 0,25 foram inseridas no modelo de regressão logística múltipla.Fatores associados com uma melhor resposta à TCCG: sexo feminino (p=0,074); melhor juízo crítico acerca dos sintomas da doença (p=0,017); melhor qualidade de vida antes do início do tratamento: domínio físico (p=0,039), domínio psicológico (p<0,001), domínio ambiental (p=0,038), domínio social (p=0,053). Fatores associados com piores resultados: maior gravidade global da doença no início do tratamento, avaliada pela CGI (p=0,007); maior número de comorbidades associadas ao TOC (p=0,063); presença de fobia social (p=0,044) e distimia (p=0,072); presença de compulsão de repetição (p=0,104).Numa segunda etapa da análise estatística, incluiu-se no modelo todas as variáveis que na primeira fase haviam apresentado associação com os resultados. As variáveis que na análise de regressão logística múltipla permaneceram associadas significativamente foram: sexo feminino (ORAjustado=2,58; p=0,021); domínio psicológico da WHOQOLBREF (ORAjustado=1,05; p=0,011); juízo crítico (ORAjustado=2,67; p=0,042) e CGI-gravidade antes do inicio da terapia (ORAjustado=0,62; p=0,045). Embora alguns fatores relacionados com a resposta ao tratamento tenham sido identificados, poder prever quais os pacientes irão aproveitar a terapia e quais não irão se beneficiar é uma questão em aberto e está longe de ser esclarecida. As razões para essas dificuldades podem estar relacionadas à heterogeneidade do TOC e das amostras utilizadas nos diferentes estudos, além da falta de padronização das técnicas psicoterápicas utilizadas. Por fim, é possível que fatores não-específicos relacionados com a pessoa do terapeuta, com a qualidade da relação terapêutica, além da motivação e capacidade de tolerar frustração por parte do paciente possam exercer um papel importante que não tem sido avaliado pelas pesquisas. / Obsessive-compulsive disorder (OCD) frequently is a chronic disorder that incapacitates about 10% of patients. Symptoms severety affect the life of patients, change their routines and cause misunderstandings with family and all those that have contact with the patient. Group cognitive-behavioral therapy (GCBT) in 12 two-hour weekly sessions is an efficient treatment that reduces OCD symptoms in over 70% of the patients and results in complete remission of symptoms in 27%. However, about 30% of the patients do not show any improvement. The knowledge of reasons why these patients do not improve and the identification of factors associated with these different therapy outcomes may help to understand OCD better, and may inform treatment indications and the development of strategies to increase its efficacy. This study included 181 patients with OCD treated with 12 session of GCBT from October 1991 to December 2006 at the Anxiety Disorders Program (Programa dos Transtornos de Ansiedade – PROTAN) of Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. The purpose of this study was to investigate predictors of response to GCBT.The following instruments were used to evaluate patients before and at the end of the treatment: Y-BOCS, Y-BOCS checklist, CGI, WHOQOL-BREF. Evaluation was conducted by means of a structured clinical interview to collect data about the patient’s symptoms, disease history, previous treatments, and OCD diagnosis according to DSM-IVTR (APA, 2002). Demographic and socioeconomic data, occupational status, use of medication and criteria for inclusion in the study were also recorded. The interview wascomplemented with the MINI (International Neuropsychiatric Interview) to investigate comorbidities. Response criteria were: >35% reduction in Y-BOCS scores and normal or borderline CGI scores at post-treatment evaluation. The study investigated the possible association of the following variables with response to treatment: sex, age at beginning of treatment, disease duration, age at onset, marital status, education, occupation, type of disease onset, disease course, intensity of OCD symptoms at beginning of treatment, insight, family history, types of symptoms, and use of antiobsessional medications during GCBT. The Pearson chi-square test was used to evaluate the association between categorical variables and response to treatment. Yates correction was performed for dichotomous variables. The Student t test for independent samples was used to evaluate quantitative variables in relation to categories of response to treatment. Variables that achieved a p value lower than 0.25 were included in the initial logistic regression model, which evaluated the predictors of response to treatment and also controlled for possible confounding variables. The following factors showed associations with response to GCBT: women had greater odds of responding to treatment (p=0.074); better insight into disease symptoms was associated with better results (p=0.017); better quality of life before the beginning of treatment was also associated with better results (physical domain: p=0.039; psychological domain: p<0.001; environmental domain: p=0.038; social domain: p=0.053); patients with greater global severity of disease according to CGI had worse results (p=0.007); a greater number of associated comorbidities (p=0.063), social phobia (p=0.044) and dysthymia (p=0.072) were associated with poorer results; repeating compulsion was also associated with lower odds of responding to treatment (p=0.104).In the second stage of statistical analysis, all variables associated with results in the first analysis were included in the multivariate model, and the variables that retained significance were: female sex (ORAdjusted=2.58; p=0.021); WHOQOL-BREF psychological domain (ORAdjusted=1.05; p=0.011); insight (ORAdjusted=2.67; p=0.042) and CGI-severity before GCBT (ORAdjusted=0.62; p=0.045). Although we identified some factors associated with response to treatment, predicting which patients will benefit from therapy and which will not is still an open question. The reasons for such different outcomes may be associated with the heterogeneity of OCD and of the samples used in different studies, as well as with the lack of standardization of the psychotherapeutic techniques used. Finally, unspecific factors not associated with the person of the therapist, the quality of the therapeutic relationship, and the patient’s motivation and tolerance to frustration may play an important role that remains to be evaluated.

O transtorno obsessivo-compulsivo (TOC) possui freqüentemente curso crônico, incapacitando cerca de 10% dos seus portadores. Os sintomas interferem de forma acentuada na vida do paciente, alterando suas rotinas e causando incompreensão dos familiares e daqueles que convivem com ele. A terapia cognitivo-comportamental em grupo (TCCG) é um tratamento eficaz, reduzindo os sintomas do TOC em mais de 70% dos portadores, sendo que ao redor de 27% obtêm remissão completa dos sintomas. Entretanto, cerca de 30% não obtêm nenhuma melhora. Conhecer as razões pelas quais esses pacientes não melhoram e identificar os fatores preditores associados ao aproveitamento ou não da terapia poderia auxiliar em uma melhor compreensão do TOC, numa melhor indicação do tratamento e no desenvolvimento de estratégias que incrementem sua eficácia. O presente estudo foi realizado com 181 pacientes com TOC, que cumpriram um programa de TCCG de 12 sessões semanais de 2 horas, entre outubro de 1999 e dezembro de 2006, no Programa de Transtornos de Ansiedade (PROTAN) do Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS) e tinha como objetivo verificar, em pacientes portadores de TOC, a existência de fatores preditores da resposta à TCCG.Os pacientes foram avaliados antes, durante e ao final do tratamento com os seguintes instrumentos: Y-BOCS, Y-BOCS chek-list, CGI, WHOQOL-BREF. Foi utilizada uma entrevista clínica estruturada com a finalidade de colher dados sobre os sintomas do paciente, histórico da doença, tratamentos anteriores e estabelecimento do diagnóstico do TOC de acordo com o DSM-IV-TR. Também foram coletados dados demográficos, socioeconômicos, status ocupacional, uso de medicação e critérios deinclusão na pesquisa. A entrevista foi complementada pelo MINI (International Neuropsychiatric Interview) para verificar a presença de comorbidades. Considerou-se como “resposta” a redução no mínimo de 35% nos escores da Y-BOCS e uma pontuação na CGI “normal” ou “limítrofe para doença” do pós para o pré-tratamento. O estudo pretende verificar se as seguintes variáveis: sexo, idade do paciente no início do tratamento, tempo de duração da doença, idade de início da doença, situação conjugal, nível de instrução, situação ocupacional, tipo de início da doença, curso, intensidade dos sintomas do TOC no início do tratamento, juízo crítico, história familiar, tipos de sintomas, uso de medicação específica para o TOC concomitante à TCCG estão associadas ou não com a resposta ao tratamento. Para avaliar a associação entre as variáveis categóricas à resposta ao tratamento, foi utilizado o teste qui-quadrado de Pearson. Nas variáveis dicotômicas foi aplicada a correção de Yates. Para avaliar as variáveis quantitativas em relação às categorias de resposta ao tratamento, foi utilizado o teste t de Student para amostras independentes. As variáveis que obtiveram um nível descritivo amostral (valor p) menor do que 0,25 foram inseridas no modelo de regressão logística múltipla.Fatores associados com uma melhor resposta à TCCG: sexo feminino (p=0,074); melhor juízo crítico acerca dos sintomas da doença (p=0,017); melhor qualidade de vida antes do início do tratamento: domínio físico (p=0,039), domínio psicológico (p<0,001), domínio ambiental (p=0,038), domínio social (p=0,053). Fatores associados com piores resultados: maior gravidade global da doença no início do tratamento, avaliada pela CGI (p=0,007); maior número de comorbidades associadas ao TOC (p=0,063); presença de fobia social (p=0,044) e distimia (p=0,072); presença de compulsão de repetição (p=0,104).Numa segunda etapa da análise estatística, incluiu-se no modelo todas as variáveis que na primeira fase haviam apresentado associação com os resultados. As variáveis que na análise de regressão logística múltipla permaneceram associadas significativamente foram: sexo feminino (ORAjustado=2,58; p=0,021); domínio psicológico da WHOQOLBREF (ORAjustado=1,05; p=0,011); juízo crítico (ORAjustado=2,67; p=0,042) e CGI-gravidade antes do inicio da terapia (ORAjustado=0,62; p=0,045). Embora alguns fatores relacionados com a resposta ao tratamento tenham sido identificados, poder prever quais os pacientes irão aproveitar a terapia e quais não irão se beneficiar é uma questão em aberto e está longe de ser esclarecida. As razões para essas dificuldades podem estar relacionadas à heterogeneidade do TOC e das amostras utilizadas nos diferentes estudos, além da falta de padronização das técnicas psicoterápicas utilizadas. Por fim, é possível que fatores não-específicos relacionados com a pessoa do terapeuta, com a qualidade da relação terapêutica, além da motivação e capacidade de tolerar frustração por parte do paciente possam exercer um papel importante que não tem sido avaliado pelas pesquisas. / Obsessive-compulsive disorder (OCD) frequently is a chronic disorder that incapacitates about 10% of patients. Symptoms severety affect the life of patients, change their routines and cause misunderstandings with family and all those that have contact with the patient. Group cognitive-behavioral therapy (GCBT) in 12 two-hour weekly sessions is an efficient treatment that reduces OCD symptoms in over 70% of the patients and results in complete remission of symptoms in 27%. However, about 30% of the patients do not show any improvement. The knowledge of reasons why these patients do not improve and the identification of factors associated with these different therapy outcomes may help to understand OCD better, and may inform treatment indications and the development of strategies to increase its efficacy. This study included 181 patients with OCD treated with 12 session of GCBT from October 1991 to December 2006 at the Anxiety Disorders Program (Programa dos Transtornos de Ansiedade – PROTAN) of Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. The purpose of this study was to investigate predictors of response to GCBT.The following instruments were used to evaluate patients before and at the end of the treatment: Y-BOCS, Y-BOCS checklist, CGI, WHOQOL-BREF. Evaluation was conducted by means of a structured clinical interview to collect data about the patient’s symptoms, disease history, previous treatments, and OCD diagnosis according to DSM-IVTR (APA, 2002). Demographic and socioeconomic data, occupational status, use of medication and criteria for inclusion in the study were also recorded. The interview wascomplemented with the MINI (International Neuropsychiatric Interview) to investigate comorbidities. Response criteria were: >35% reduction in Y-BOCS scores and normal or borderline CGI scores at post-treatment evaluation. The study investigated the possible association of the following variables with response to treatment: sex, age at beginning of treatment, disease duration, age at onset, marital status, education, occupation, type of disease onset, disease course, intensity of OCD symptoms at beginning of treatment, insight, family history, types of symptoms, and use of antiobsessional medications during GCBT. The Pearson chi-square test was used to evaluate the association between categorical variables and response to treatment. Yates correction was performed for dichotomous variables. The Student t test for independent samples was used to evaluate quantitative variables in relation to categories of response to treatment. Variables that achieved a p value lower than 0.25 were included in the initial logistic regression model, which evaluated the predictors of response to treatment and also controlled for possible confounding variables. The following factors showed associations with response to GCBT: women had greater odds of responding to treatment (p=0.074); better insight into disease symptoms was associated with better results (p=0.017); better quality of life before the beginning of treatment was also associated with better results (physical domain: p=0.039; psychological domain: p<0.001; environmental domain: p=0.038; social domain: p=0.053); patients with greater global severity of disease according to CGI had worse results (p=0.007); a greater number of associated comorbidities (p=0.063), social phobia (p=0.044) and dysthymia (p=0.072) were associated with poorer results; repeating compulsion was also associated with lower odds of responding to treatment (p=0.104).In the second stage of statistical analysis, all variables associated with results in the first analysis were included in the multivariate model, and the variables that retained significance were: female sex (ORAdjusted=2.58; p=0.021); WHOQOL-BREF psychological domain (ORAdjusted=1.05; p=0.011); insight (ORAdjusted=2.67; p=0.042) and CGI-severity before GCBT (ORAdjusted=0.62; p=0.045). Although we identified some factors associated with response to treatment, predicting which patients will benefit from therapy and which will not is still an open question. The reasons for such different outcomes may be associated with the heterogeneity of OCD and of the samples used in different studies, as well as with the lack of standardization of the psychotherapeutic techniques used. Finally, unspecific factors not associated with the person of the therapist, the quality of the therapeutic relationship, and the patient’s motivation and tolerance to frustration may play an important role that remains to be evaluated.

Introduction : L’élastographie shear wave (ESW) est une technique récente d’échographie qui évalue quantitativement la dureté des tissus et permet d’améliorer la caractérisation des lésions mammaires. Comme toute nouvelle technique d’imagerie, l’ESW nécessite une validation préclinique pour définir les conditions d’utilisations et établir les limites des champs d’applications dans lesquelles la technique pourra être considérée comme valide. Matériels et méthodes : Dans une première partie effectuée au laboratoire de recherche en Imagerie nous avons étudié les éléments histologiques sous tendant l’image d’ESW sur un modèle de cancer du sein implanté chez la souris, au cours de sa croissance puis sous traitement. Dans une deuxième partie, nous avons étudié chez des patientes le rôle de la compression manuelle en ESW pour la caractérisation des lésions mammaires. Dans une dernière partie, effectuée en collaboration avec une équipe de l’Institut Langevin Ondes et Images, nous avons étudié la faisabilité d’un nouveau paramètre, le module de cisaillement non linéaire pour l’analyse des lésions mammaires. Résultats : Au laboratoire, nous avons établi des corrélations entre la dureté mesurée en élastographie et les caractéristiques histologiques des tumeurs, y compris sous traitement. Nous avons montré que la fibrose était associée à une dureté élevée et la nécrose à une dureté moindre. Notre étude clinique a montré qu’une compression manuelle minimale était nécessaire pour obtenir de bonnes performances de l’ESW et qu’une pression trop élevée devait être évitée. Enfin nous avons montré la faisabilité en imagerie mammaire d’un nouveau paramètre quantitatif obtenu en élastographie shear wave : le module de cisaillement non linéaire. Conclusion : A partir de travail de thèse, une meilleure compréhension de la part des éléments biologiques et techniques en ESW du sein est possible et des recommandations pour l’utilisation clinique peuvent être formulées. Nos observations cliniques ont entrainé la mise au point d’un nouveau paramètre diagnostique quantitatif : le module de cisaillement non linéaire. / Introduction: Shear Wave Elastography (SWE) is a recent ultrasound technique assessing quantitatively tissue stiffness and improving breast lesions characterization. As every new imaging technique, SWE requires a pre clinical validation in order to define in which conditions it should be used and precise the applications for which the technique is validated. Materials and methods: First, in a research lab we have investigated the pathological features underlying SWE image in a breast cancer model implanted in mice, during tumor growth and under therapy. Secondly, we have studied in patients the role of manual compression in SWE for the characterization of breast lesions. Finally, in collaboration with on team from Institut Langevin Ondes et Images, we have studied the feasibility of a new parameter, the non-linear modulus, for breast lesion assessment. Results: in the research lab, we have shown correlations between stiffness as measured with SWE and pathological features of tumors, even on treatment. We have shown that fibrosis was associated with high stiffness values and necrosis with lowers. Our clinical study, showed that a minimal manual compression was required for optimal performance of SWE and that strong compression should be avoided. Finally, we demonstrated feasibility of a new parameter, derived from SWE, the non-linear modulus. Conclusion: Our work provides a better understanding of biological and technical elements of SWE. On the basis of our results, new recommendations may be made for the use of SWE in clinical practice. From our clinical findings, we developed a new quantitative parameter, which may be useful for the diagnosis of breast lesions, the non-linear modulus.