Diss. (sammanfattning) Stockholm : Karolinska institutet, 2001. / Härtill 5 uppsatser.

The total annual incidence of arthritis in this prospective cross-sectional study on adults was 115/100 000. The annual incidence of rheumatoid arthritis (RA) was 24/100 000, 29/100 000 for women, and 18/100 000 for men. For reactive arthritis (ReA) the annual incidence was slightly higher, 28/100 000, and for undifferentiated arthritis 41/100 000. The annual incidence of Lyme disease and sarcoid arthritis was low. The annual incidence of arthritis in this study compares well with findings in earlier reports from both registers and case review studies. Almost 50% of the patients in the series of 71 patients with arthritis of less than 3 months’ duration had a preceding infection. Campylobacter jejuni ReA dominated the enteric ReA group. We found only a few patients with preceding Chl. trachomatis, Chl. pneumoniae, Borrelia burgdorferi or parvovirus B19 infections. The arthritis patients with a preceding infection went into remission more often than the patients without a preceding infection. The disease specificity of anti-CCP antibodies for RA was high, 96%, confirming earlier results. Anti-CCP antibodies differentiated RA from other arthritides. Several patients in the different diagnosis groups had raised serum COMP levels, indicating cartilage involvement very early in the disease, even in mild and self-limiting disease with good prognosis. The economic burden of early joint inflammation was found to be considerable already during the first few months of the arthritis irrespective of diagnosis. Surprisingly, patients with ReA generated almost as high costs as patients with RA during thefirst few months of the disease, even though most of the ReA patients had a relatively mild disease. Sick leave accounted for about 50% of the costs. The distribution of costs in the different patient groups was skewed. The median cost per patient for the group of patients with RA was US$4385, for ReA US$4085, for other types of specified arthritis US$3361, and for undifferentiated arthritis US$1482. This underlines the necessity of quick referral and therapy, not only to decrease the inflammation and prevent functional impairment, but also to decrease the costs of early arthritis.

Diss. (sammanfattning) Stockholm : Karol inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol inst., 2004. / Härtill 4 uppsatser.

In conclusion, gene expression profiling in blood may have potential to be an adjuvant marker for early detection of AD. Expression marker panel is more informative than single gene expression signature. Further validation in prospective studies will substantiate its clinical application and explore its potential to differentiate AD from other dementias and to predict the progression from MCI to AD. (Abstract shortened by UMI.) / In the study, the profile of 12 target gene expression levels in peripheral blood cells were determined in 96 AD, 145 MCI and 167 normal controls (NC) by quantitative real-time RT-PCR. The genes were identified with (i) high expression in blood and brain; (ii) differential expression between AD and control; (iii) AD related candidate genes. Then, a list of genes were selected including CTSB, CTSD, DDT, ITPKB, NDUFA6, NRD1, PIN1, SNX2, TSC1, UQCRC1, CNR2, GSTM3. Seven genes were found to be differentially expressed between AD and NC group, with upregulation of CTSB, CTSD, DDT, TSC1 and UQCRC1, and downregulation of ITPKB and PIN1 in AD patients. Expression levels of two genes were increased in the MCI compared with NC group, including CTSB and CTSD. In addition, an upregulation of CTSD, UQCRC1, NRD1 and downregulation of ITPKB were observed in AD subjects in comparison to the MCI group (Mann-Whitney U test, p<0.05). After adjusting for confounding factors of age, gender, education level, ApoE4 status and the total CIRS score, expression level of any single gene was not associated with the classfication of AD or MCI (Logistic regression, p>0.05). A five gene biomarker panel, including DDT, ITPKB, PIN1, TSC1 and UQCRC1 was identified with logistic regression analysis. The function of Logit(P)= ln(P/(1-P))= b0+b1RatioDDT+ b2RatioITPKB + b3Ratio PIN1 +b4 RatioTSC1+b5Ratio UQCRC1 were defined as the probability of a subject to be diagnosed as "AD" or "MCI' by using 5-gene biomarker panel. ROC analysis showed that the AUC for the 5-gene biomarkers panel in differentiating between AD and NC, between MCI and NC, between AD and MCI were 0.79 (95% CI, 0.72-0.86; p<0.001), 0.61 (95% CI, 0.53-0.69; p=0.007) and 0.68 (95% CI, 0.60-0.76; p<0.001) respectively. The 5-gene combination was found to discriminate AD subjects from normal controls with good sensitivity and specificity of 70.7% and 86.7% respectively at an optimal cut-off point of 0.486. Low sensitivity (42.4%) and acceptable specificity (76.2%) were observed at a cut-off threshold of 0.505 when differentiating MCI from NC subjects. Between AD and MCI subjects, gene combination showed a sensitivity of 61% and specificity of 73.7% at a cut-off value of 0.496. / Several genes including CTSD, DDT, NDUFA6, TSC1 and UQCRC1 were found in association with the cognitive and psychiatric symptoms, indicating the role of genetic factors in moderating the presence of cognitive and NP profiles in demented individuals. / The aim of the present study is to evaluate the gene expression profiling of peripheral leukocytes in Chinese subjects with Alzheimer's disease (AD) and explored its potential of clinical application. Behavioral phenotypes of cognitive performance and neuropsychiatric assessment were also investigated in association with gene expression in AD. Persons with mild cognitive impairment (MCI), as an at-risk state between normal aging and clinical dementia, was also assessed in consideration that the information may provide a better understanding of the mechanisms involved in clinical progression of AD. / The genes identified in this study were involved in processes implicated in neurodegneration, including protein isomerization (PIN1), calcium disequilibrium and mitochondria insufficiency (ITPKB and UQCRC1), increased inflammatory response (DDT), apoptosis (CTSB and CTSD) and neurogeneration (NRD1 and TSC1). / Fu, Yan. / Adviser: Chiu Wa Lam. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 132-168). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

A ecocardiografia é um importante exame no diagnóstico de insuficiência cardíaca, avaliando as funções, sistólica e diastólica, comprometidas nesta síndrome. Pacientes com insuficiência cardíaca apresentando disfunção sistólica esquerda constituem uma população com alta morbidade e mortalidade, tendo sido descritos diversos parâmetros ecocardiográficos marcadores de prognóstico. Recentemente, desenvolveram-se metodologias que possibilitam avaliar a sincronia mecânica do coração que se apresenta especialmente comprometida nesta população. No entanto, o valor destas medidas em estimar o risco de eventos clínicos adversos é incerto. O objetivo deste estudo foi o de testar se estas medidas ecocardiográficas podem constituir marcadores de eventos cardíacos adversos em pacientes clinicamente estáveis com insuficiência cardíaca e disfunção sistólica esquerda. Duzentos e sete pacientes encaminhados consecutivamente dos ambulatórios de Insuficiência Cardíaca e Miocardiopatias, em condição clínica estável e com medicação otimizada realizaram um ecocardiograma, coletando-se nesta data: dados clínicos, eletrocardiográficos e amostras de sangue. No ecocardiograma, avaliaram-se além das medidas convencionais, aquelas que descrevem a sincronia: atrial esquerda, atrioventricular, interventricular, intraventriculares diastólica e sistólica, esta última por cinco metodologias distintas. Acompanharam-se estes pacientes por 1,5±0.9 anos. Por meio da regressão logística de Cox, analisaram-se estes dados como marcadores dependentes ou independentes de desfecho principal (óbito ou transplante cardíaco) e secundário (óbito, transplante cardíaco ou hospitalização por descompensação da insuficiência cardíaca). As características e frequências mais marcantes do grupo foram: sexo masculino - 64%, idade 58±13 anos, Classe funcional II/III - NYHA 70%, doença arterial coronariana 40%, uso de inibidores de enzima de conversão ou bloqueador dos receptores de angiotensina II 93%, uso de betabloqueadores 90%, intervalo QRS 148±31 ms, bloqueio de ramo esquerdo 57%, diâmetro diastólico do ventrículo esquerdo 72±9 mm, fração de ejeção do ventrículo esquerdo 30±5 %, disfunção diastólica grau III ou IV 46%, insuficiência mitral mais que discreta 19%. Nenhuma variável ecocardiográfica que avalia a sincronia mecânica foi marcadora destes eventos. Na análise multivariada pelo modelo de Cox, as variáveis associadas ao desfecho primário foram: sexo feminino HR, 0,14 (p=0.01), Classe funcional III - NYHA, HR 14,64 (p<0.01), índice de massa cardíaca cada 10 g, HR 1,16 (p<0,01), fração de ejeção do ventrículo esquerdo cada 5%, HR 0,44 (<0,01) e a fração de esvaziamento ativo do átrio esquerdo cada 10%, HR 0,38 (p<0,01). Para o desfecho secundário, as variáveis que se associaram foram: Classe funcional III - NYHA, HR 8,50 (p<0,01), índice de massa cardíaca cada 10 g, HR 1,06 (p=0,04), fração de esvaziamento ativo do átrio esquerdo cada 10%, HR 0,69 (p=0,01) e a integral do Doppler da via de saída do ventrículo esquerdo cada 5 cm, HR 0,65 (p=0,03). Os resultados deste estudo indicam que as medidas ecocardiográficas de sincronia cardíaca não se apresentam como marcadores prognósticos de pacientes clinicamente estáveis, portadores de insuficiência cardíaca com disfunção sistólica esquerda. / Echocardiography is a diagnostic tool to establish clinical diagnosis of heart failure, accurately evaluating heart\'s dysfunction, systolic and/or diastolic, existing in this syndrome. Heart failure patients with systolic left ventricular dysfunction constitute a population with high morbidity and mortality, have being described several echocardiographic prognostic factors. Recently, new methodologies enable the evaluation of mechanical synchrony of the heart that compromises frequently this particular population. However, the value of these measurements to estimate risk of adverse clinical events in such patients is uncertain. The purpose of this study was to test whether these echocardiographic measurements can predict cardiac adverse events in heart failure patients, clinically stable, with left ventricular systolic dysfunction. Two hundred and seven patients referred consecutively from outpatient heart failure clinics, in stable clinical condition, with optimized medication did an echocardiogram collecting also clinical, electrocardiographic data and blood samples. There were evaluated in addition to conventional echocardiographic measurements, those that describe the various types of synchrony: left atrial, atriovenricular, interventricular, intraventricular diastolic and systolic, the latter by five distinct methods. The follow up was 1.5 ± 0.9 years. By Cox regression, we analyzed if these data were dependent or independent predictors of primary (death or cardiac transplantation) and secondary outcome (death, heart transplantation or hospitalization for heart failure decompensation). The most remarkable features and frequencies of this group were: male gender- 64%, age 58 ± 13 years, functional class II / III - NYHA 70%, known coronary artery disease 40%, use of converting enzyme inhibitor or receptor blocker angiotensin II 93%, beta-blockers 90%, QRS interval 148 ± 31 ms, left bundle branch block 57%, left ventricular diastolic diameter 72 ± 9 mm, left ventricular ejection fraction 30 ± 5%, diastolic dysfunction grade III or IV 46%, mitral regurgitation - more than mild 19%. None of the echocardiographic variables that evaluate mechanical synchrony predicted these events. On Cox multivariate regression, the variables associated to the primary outcome were: female gender, HR 0.14 (p = 0.01), functional class III - NYHA, HR 14.64 (p <0.01), cardiac mass index - every 10 g, HR 1.16 (p <0.01), ejection fraction, left ventricular - every 5 %, HR 0.44 (p <0.01) and left atrial active emptying fraction - every 10%, HR 0.38 (p <0.01). For the secondary outcome, the variables associated were: functional class III - NYHA, HR 8.50 (p <0.01), cardiac mass index - every 10 g, HR 1, 06 (p = 0.04), left atrial active emptying fraction - every 10%, HR 0.69 (p = 0.01) and the integral of left ventricle outflow Doppler - every 5 cm, HR 0.65 (p= 0.03). The results of this study indicate that echocardiographic measurements of cardiac synchrony are not predictors of cardiac events of clinically stable heart failure patients with systolic left ventricular dysfunction.

A ecocardiografia é um importante exame no diagnóstico de insuficiência cardíaca, avaliando as funções, sistólica e diastólica, comprometidas nesta síndrome. Pacientes com insuficiência cardíaca apresentando disfunção sistólica esquerda constituem uma população com alta morbidade e mortalidade, tendo sido descritos diversos parâmetros ecocardiográficos marcadores de prognóstico. Recentemente, desenvolveram-se metodologias que possibilitam avaliar a sincronia mecânica do coração que se apresenta especialmente comprometida nesta população. No entanto, o valor destas medidas em estimar o risco de eventos clínicos adversos é incerto. O objetivo deste estudo foi o de testar se estas medidas ecocardiográficas podem constituir marcadores de eventos cardíacos adversos em pacientes clinicamente estáveis com insuficiência cardíaca e disfunção sistólica esquerda. Duzentos e sete pacientes encaminhados consecutivamente dos ambulatórios de Insuficiência Cardíaca e Miocardiopatias, em condição clínica estável e com medicação otimizada realizaram um ecocardiograma, coletando-se nesta data: dados clínicos, eletrocardiográficos e amostras de sangue. No ecocardiograma, avaliaram-se além das medidas convencionais, aquelas que descrevem a sincronia: atrial esquerda, atrioventricular, interventricular, intraventriculares diastólica e sistólica, esta última por cinco metodologias distintas. Acompanharam-se estes pacientes por 1,5±0.9 anos. Por meio da regressão logística de Cox, analisaram-se estes dados como marcadores dependentes ou independentes de desfecho principal (óbito ou transplante cardíaco) e secundário (óbito, transplante cardíaco ou hospitalização por descompensação da insuficiência cardíaca). As características e frequências mais marcantes do grupo foram: sexo masculino - 64%, idade 58±13 anos, Classe funcional II/III - NYHA 70%, doença arterial coronariana 40%, uso de inibidores de enzima de conversão ou bloqueador dos receptores de angiotensina II 93%, uso de betabloqueadores 90%, intervalo QRS 148±31 ms, bloqueio de ramo esquerdo 57%, diâmetro diastólico do ventrículo esquerdo 72±9 mm, fração de ejeção do ventrículo esquerdo 30±5 %, disfunção diastólica grau III ou IV 46%, insuficiência mitral mais que discreta 19%. Nenhuma variável ecocardiográfica que avalia a sincronia mecânica foi marcadora destes eventos. Na análise multivariada pelo modelo de Cox, as variáveis associadas ao desfecho primário foram: sexo feminino HR, 0,14 (p=0.01), Classe funcional III - NYHA, HR 14,64 (p<0.01), índice de massa cardíaca cada 10 g, HR 1,16 (p<0,01), fração de ejeção do ventrículo esquerdo cada 5%, HR 0,44 (<0,01) e a fração de esvaziamento ativo do átrio esquerdo cada 10%, HR 0,38 (p<0,01). Para o desfecho secundário, as variáveis que se associaram foram: Classe funcional III - NYHA, HR 8,50 (p<0,01), índice de massa cardíaca cada 10 g, HR 1,06 (p=0,04), fração de esvaziamento ativo do átrio esquerdo cada 10%, HR 0,69 (p=0,01) e a integral do Doppler da via de saída do ventrículo esquerdo cada 5 cm, HR 0,65 (p=0,03). Os resultados deste estudo indicam que as medidas ecocardiográficas de sincronia cardíaca não se apresentam como marcadores prognósticos de pacientes clinicamente estáveis, portadores de insuficiência cardíaca com disfunção sistólica esquerda. / Echocardiography is a diagnostic tool to establish clinical diagnosis of heart failure, accurately evaluating heart\'s dysfunction, systolic and/or diastolic, existing in this syndrome. Heart failure patients with systolic left ventricular dysfunction constitute a population with high morbidity and mortality, have being described several echocardiographic prognostic factors. Recently, new methodologies enable the evaluation of mechanical synchrony of the heart that compromises frequently this particular population. However, the value of these measurements to estimate risk of adverse clinical events in such patients is uncertain. The purpose of this study was to test whether these echocardiographic measurements can predict cardiac adverse events in heart failure patients, clinically stable, with left ventricular systolic dysfunction. Two hundred and seven patients referred consecutively from outpatient heart failure clinics, in stable clinical condition, with optimized medication did an echocardiogram collecting also clinical, electrocardiographic data and blood samples. There were evaluated in addition to conventional echocardiographic measurements, those that describe the various types of synchrony: left atrial, atriovenricular, interventricular, intraventricular diastolic and systolic, the latter by five distinct methods. The follow up was 1.5 ± 0.9 years. By Cox regression, we analyzed if these data were dependent or independent predictors of primary (death or cardiac transplantation) and secondary outcome (death, heart transplantation or hospitalization for heart failure decompensation). The most remarkable features and frequencies of this group were: male gender- 64%, age 58 ± 13 years, functional class II / III - NYHA 70%, known coronary artery disease 40%, use of converting enzyme inhibitor or receptor blocker angiotensin II 93%, beta-blockers 90%, QRS interval 148 ± 31 ms, left bundle branch block 57%, left ventricular diastolic diameter 72 ± 9 mm, left ventricular ejection fraction 30 ± 5%, diastolic dysfunction grade III or IV 46%, mitral regurgitation - more than mild 19%. None of the echocardiographic variables that evaluate mechanical synchrony predicted these events. On Cox multivariate regression, the variables associated to the primary outcome were: female gender, HR 0.14 (p = 0.01), functional class III - NYHA, HR 14.64 (p <0.01), cardiac mass index - every 10 g, HR 1.16 (p <0.01), ejection fraction, left ventricular - every 5 %, HR 0.44 (p <0.01) and left atrial active emptying fraction - every 10%, HR 0.38 (p <0.01). For the secondary outcome, the variables associated were: functional class III - NYHA, HR 8.50 (p <0.01), cardiac mass index - every 10 g, HR 1, 06 (p = 0.04), left atrial active emptying fraction - every 10%, HR 0.69 (p = 0.01) and the integral of left ventricle outflow Doppler - every 5 cm, HR 0.65 (p= 0.03). The results of this study indicate that echocardiographic measurements of cardiac synchrony are not predictors of cardiac events of clinically stable heart failure patients with systolic left ventricular dysfunction.

Thesis (M.S.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).