Para avaliar a reserva adrenal após o uso de glicocorticóide na fase de indução de remissão em pacientes com Leucemia Linfocítica Aguda, estudo duplo-cego foi realizado em 29 crianças e adolescentes de 1,7 a 15,9 anos (média:6,8 anos], que receberam por escolha aleatória, Prednisona na dose de 40 mg/m²/dia ou Dexametasona, 6 mg/m²/dia, via oral, por um mês. Testes do ACTH em baixa dose (1,0 µg/m² EV) foram realizados antes e a cada 7 dias por 8 semanas para avaliar pico de cortisol após o estímulo. Não houve diferença significativa entre as médias dos picos de cortisol nos testes realizados em cada grupo e entre os dois grupos, mostrando reserva adrenal adequada. Não houve correlação entre os picos de cortisol nos dois grupos e a presença de infecção / In order to evaluate adrenal reserve after adminstration of glucocorticoid during induction phase in patients with Acute LymphociticLeukemia, a double-blind study was performed in 29 children and adolescents 1,7 to 15.9 years old (mean: 6.8 years old), who randomly were chosen to receive either Prednisone, 40 mg/m²/day or Dexamethasone, 6 mg/m²/day, PO, for one month. Low-dose ACTH tests (1.0 µg/m² IV), were performed before and every 7 days after glucocorticoid for 8 weeks. There were no significant differences of cortisol mean peak levels in the tests of each group and in both group, suggesting adequate adrenal reserve. There was no correlation of cortisol mean peak levels in both groups and the presence of infection

Introdução: As infecções são importantes causas de morbidade e mortalidade em pacientes com lúpus eritematoso sistêmico juvenil (LESJ). No entanto, estudos avaliando somente infecções fúngicas invasivas (IFI) em pacientes com LESJ são restritos a relatos de casos ou série de casos, sem qualquer avaliação sistemática dos possíveis fatores de risco ou desfechos associados. A escassez de dados referentes às IFI em pacientes com LESJ e seu impacto sobre as características da doença em uma grande população levou ao desenvolvimento deste estudo multicêntrico. Objetivos: Estudar a prevalência, fatores de risco e mortalidade de IFI em pacientes com LESJ. Método: Um estudo de coorte multicêntrico retrospectivo foi realizado com 852 pacientes com LESJ de 10 Serviços de Reumatologia Pediátrica do Estado de São Paulo. Uma reunião foi realizada e todos os pesquisadores foram treinados para o preenchimento do banco de dados. As IFI foram diagnosticadas de acordo com as definições revisadas pelo grupo de consenso EORTC/MSG (comprovadas, prováveis ou possíveis). Foram coletados dados acerca de dados demográficos, características clínico-laboratoriais, atividade da doença (SLEDAI-2K), dano cumulativo (SLICC/ACR-DI) e tratamento, além de características e complicações das IFI. Resultados: IFI foram diagnosticadas em 33/852 (3,9%) pacientes com LESJ. IFI comprovadas foram diagnosticadas em 22 pacientes, IFI prováveis em 5 e IFI possíveis em 6. Os tipos de IFI encontradas foram: candidíase em 20 pacientes, aspergilose em 9, criptococose em 2, histoplasmose disseminada em um e paracoccidioidomicose em um. A mediana de duração da doença foi menor (1,0 vs. 4,7 anos, p < 0,0001), com maiores escores de SLEDAI-2K atual [19,5 (0-44) vs. 2 (0-45), p < 0,0001] e dose atual de prednisona [50 (10-60) vs. 10 (2-90) mg/dia, p < 0,0001] em pacientes com IFI em comparação com os pacientes sem IFI. A frequência de óbito foi maior no grupo com IFI (51% vs. 6%, p < 0,0001). A análise de regressão logística revelou que SLEDAI-2K atual (OR=1,108, IC 95%=1,057- 1,163, p < 0,0001), dose atual de prednisona (OR=1,046, IC 95%=1,021-1,071; p < 0,0001) e duração da doença (OR=0,984, IC 95%=0,969-0,998, p=0,030) foram fatores de risco independentes para IFI (R2 Nagelkerke 0,425). Conclusão: Este foi o primeiro estudo que caracterizou IFI em pacientes com LESJ. Identificou-se que a atividade da doença e uso de glicocorticoides foram os principais fatores de risco para estas infecções potencialmente graves, principalmente nos primeiros anos de curso da doença e com uma elevada taxa mortalidade / Introduction: Infections are an important cause of morbidity and mortality in childhoodonset systemic lupus erythematosus (cSLE) patients. However, studies evaluating solely invasive fungal infections (IFI) in cSLE patients are restricted to case reports or case series without any systematic evaluation of the possible associated risk factors and outcome in pediatric lupus population. The scarcity of data regarding IFI in cSLE patients and its impact on disease characteristics in a large population led to the development of this multicenter study. Objective: To study the prevalence, risk factors and mortality of IFI in cSLE patients. Methods: A retrospective multicenter cohort study was performed in 852 cSLE patients from 10 Pediatric Rheumatology services. An investigator meeting was held and all participants received database training. IFI were diagnosed according to EORTC/MSG Consensus Group criteria (proven, probable and possible). Demographic data, clinical, laboratorial, disease activity (SLEDAI-2K), cumulative damage (SLICC/ACR-DI) and treatment were collected. IFI were characterized and its outcome were also evaluated. Results: IFI were observed in 33/852 (3.9%) cSLE patients. Proven IFI was diagnosed in 22 cSLE patients, probable IFI in 5 and possible IFI in 6. Types of IFI were: 20 candidiasis, 9 aspergillosis, 2 cryptococcosis, one disseminated histoplasmosis and one paracoccidioidomycosis. The median of disease duration was lower (1.0 vs. 4.7 years, p < 0.0001), with a higher current SLEDAI-2K [19.5 (0-44) vs. 2 (0-45), p < 0.0001] and current prednisone dose [50 (10-60) vs. 10 (2-90) mg/day, p < 0.0001] in patients with IFI compared to those without IFI. The frequency of death was higher in the former group (51% vs. 6%, p < 0.0001). Logistic regression analysis revealed that current SLEDAI-2K (OR=1.108; 95%CI=1.057-1.163; p < 0.0001), prednisone current dose (OR=1.046; 95%CI=1.021-1.071; p < 0.0001) and disease duration (OR=0.984; 95%CI=0.969-0.998; p=0.03) were independent risk factors for IFI (R2 Nagelkerke 0.425). Conclusion: This was the first study that characterized IFI in cSLE patients. We identified that disease activity and glucocorticoid use were the main risk factors for these life-threatening infections, mainly in the first years of disease course and with a high rate of fatal outcome

Introdução: As infecções são importantes causas de morbidade e mortalidade em pacientes com lúpus eritematoso sistêmico juvenil (LESJ). No entanto, estudos avaliando somente infecções fúngicas invasivas (IFI) em pacientes com LESJ são restritos a relatos de casos ou série de casos, sem qualquer avaliação sistemática dos possíveis fatores de risco ou desfechos associados. A escassez de dados referentes às IFI em pacientes com LESJ e seu impacto sobre as características da doença em uma grande população levou ao desenvolvimento deste estudo multicêntrico. Objetivos: Estudar a prevalência, fatores de risco e mortalidade de IFI em pacientes com LESJ. Método: Um estudo de coorte multicêntrico retrospectivo foi realizado com 852 pacientes com LESJ de 10 Serviços de Reumatologia Pediátrica do Estado de São Paulo. Uma reunião foi realizada e todos os pesquisadores foram treinados para o preenchimento do banco de dados. As IFI foram diagnosticadas de acordo com as definições revisadas pelo grupo de consenso EORTC/MSG (comprovadas, prováveis ou possíveis). Foram coletados dados acerca de dados demográficos, características clínico-laboratoriais, atividade da doença (SLEDAI-2K), dano cumulativo (SLICC/ACR-DI) e tratamento, além de características e complicações das IFI. Resultados: IFI foram diagnosticadas em 33/852 (3,9%) pacientes com LESJ. IFI comprovadas foram diagnosticadas em 22 pacientes, IFI prováveis em 5 e IFI possíveis em 6. Os tipos de IFI encontradas foram: candidíase em 20 pacientes, aspergilose em 9, criptococose em 2, histoplasmose disseminada em um e paracoccidioidomicose em um. A mediana de duração da doença foi menor (1,0 vs. 4,7 anos, p < 0,0001), com maiores escores de SLEDAI-2K atual [19,5 (0-44) vs. 2 (0-45), p < 0,0001] e dose atual de prednisona [50 (10-60) vs. 10 (2-90) mg/dia, p < 0,0001] em pacientes com IFI em comparação com os pacientes sem IFI. A frequência de óbito foi maior no grupo com IFI (51% vs. 6%, p < 0,0001). A análise de regressão logística revelou que SLEDAI-2K atual (OR=1,108, IC 95%=1,057- 1,163, p < 0,0001), dose atual de prednisona (OR=1,046, IC 95%=1,021-1,071; p < 0,0001) e duração da doença (OR=0,984, IC 95%=0,969-0,998, p=0,030) foram fatores de risco independentes para IFI (R2 Nagelkerke 0,425). Conclusão: Este foi o primeiro estudo que caracterizou IFI em pacientes com LESJ. Identificou-se que a atividade da doença e uso de glicocorticoides foram os principais fatores de risco para estas infecções potencialmente graves, principalmente nos primeiros anos de curso da doença e com uma elevada taxa mortalidade / Introduction: Infections are an important cause of morbidity and mortality in childhoodonset systemic lupus erythematosus (cSLE) patients. However, studies evaluating solely invasive fungal infections (IFI) in cSLE patients are restricted to case reports or case series without any systematic evaluation of the possible associated risk factors and outcome in pediatric lupus population. The scarcity of data regarding IFI in cSLE patients and its impact on disease characteristics in a large population led to the development of this multicenter study. Objective: To study the prevalence, risk factors and mortality of IFI in cSLE patients. Methods: A retrospective multicenter cohort study was performed in 852 cSLE patients from 10 Pediatric Rheumatology services. An investigator meeting was held and all participants received database training. IFI were diagnosed according to EORTC/MSG Consensus Group criteria (proven, probable and possible). Demographic data, clinical, laboratorial, disease activity (SLEDAI-2K), cumulative damage (SLICC/ACR-DI) and treatment were collected. IFI were characterized and its outcome were also evaluated. Results: IFI were observed in 33/852 (3.9%) cSLE patients. Proven IFI was diagnosed in 22 cSLE patients, probable IFI in 5 and possible IFI in 6. Types of IFI were: 20 candidiasis, 9 aspergillosis, 2 cryptococcosis, one disseminated histoplasmosis and one paracoccidioidomycosis. The median of disease duration was lower (1.0 vs. 4.7 years, p < 0.0001), with a higher current SLEDAI-2K [19.5 (0-44) vs. 2 (0-45), p < 0.0001] and current prednisone dose [50 (10-60) vs. 10 (2-90) mg/day, p < 0.0001] in patients with IFI compared to those without IFI. The frequency of death was higher in the former group (51% vs. 6%, p < 0.0001). Logistic regression analysis revealed that current SLEDAI-2K (OR=1.108; 95%CI=1.057-1.163; p < 0.0001), prednisone current dose (OR=1.046; 95%CI=1.021-1.071; p < 0.0001) and disease duration (OR=0.984; 95%CI=0.969-0.998; p=0.03) were independent risk factors for IFI (R2 Nagelkerke 0.425). Conclusion: This was the first study that characterized IFI in cSLE patients. We identified that disease activity and glucocorticoid use were the main risk factors for these life-threatening infections, mainly in the first years of disease course and with a high rate of fatal outcome

The cancer recognition (CARE) antibody (Ab) test is a serologic assay for a specific IgM that is elevated in cancer patients. All tests are measured using an indirect enzyme-linked immunosorbent assay (ELISA) of human serum. The target polypeptide in the CARE Ab test is the IgM binding epitope (LT-11) of the CARE antigen (Ag) consisting of a 16 mer structure that has been produced synthetically. The mean relative concentration (MRC) is determined relative to standard, normalized human plasma. Non-parametric analysis showed median MRC values of healthy volunteers (HVs) with no history of cancer (n=47), family history of cancer (n=126) and a previous cancer history (n=24) to be 26, 34 and 46, respectively. It was determined that there was no significance found among the medians of the three HV groups (P=0.53). The specificity of the HV types was between 87 and 98%. Benign/non-cancer surgical patients (n=27) had a median value of 20 with a specificity of 96%. The cancer patients (n=61) had a median value of 246 with a sensitivity of 89%. There was a significant difference between the HV and cancer patients (P<0.0001) as well as between the benign/surgical non-cancerous group and cancer patients (P<0.0001). The IgM antibody is heat stable at room temperature for two days versus being frozen at -80°C (r2=0.97). Either serum or plasma samples may be used in the CARE Ab test (r2=0.92). The CARE Ab was almost exclusively IgM with no serum conversion to IgG in sequential measurements of patients with cancer over a six-month period. Preliminary data from patients undergoing post-operative cancer treatment showed that decreasing Ab levels revealed patients negative for residual cancer or undergoing remission, while relapsing patients show an increase in Ab levels. A return to a positive Ab level shortly after treatment is a poor prognostic sign while in advanced cancers the Ab levels may be depressed significantly.

Objetivos: Avaliar a estatura final, mineralização e marcadores de mineralização óssea de adultos com síndrome nefrótica (SN) idiopática corticossensível na infância e adolescência e analisar a influência da doença, suas comorbidades e do alvo de estatura no crescimento e mineralização destes pacientes. Casuística: Avaliamos a estatura final de 60 pacientes (41 masculinos e 19 femininos) com idade mínima de dezenove anos ou desenvolvimento genital P4G4 nos masculinos e menarca nos femininos portadores de SN corticossensível na infância e adolescência. Realizamos a densitometria óssea (DMO=g/cm2) em 26 destes pacientes e em 35 controles, com análise concomitante dos níveis séricos de 25 OH vitamina D3 (25(OH)D), Paratormônio (PTH), telopéptido carboxiterminal do colágeno tipo 1( (CTx), Propeptídeo Aminoterminal do Colágeno Tipo I (P1NP) e Osteocalcina (OC) Resultados: A idade média inicial dos 60 pacientes foi de 5a3m e final de 20a5m, com acompanhamento médio de 15a2m. A dose média de prednisona utilizada foi de 1264 mg/kg. O Zscore médio da estatura inicial (-0,60; SD: 1,0) e final (0,64; SD: 0,92), não diferiu significativamente (Teste T: p=0,72) entre si. O Zscore estatura na idade adulta se correlacionou significativamente apenas com o Zscore estatura inicial e com o Zscore alvo de estatura. Seis pacientes atingiram Zscore estatura < -2 na idade adulta e este achado demonstrou forte correlação com o Zscore estatura inicial e com o Zscore alvo de estatura. A DMO e Zscore DMO de L1L4, Cabeça do fêmur e do Fêmur total dos pacientes e controles não diferiram significativamente. 6 pacientes e 2 controles apresentaram Zscore DMO < -2 (massa óssea reduzida) enquanto 2 pacientes e 1 controle demonstraram , Zscore DMO < -2,5 (osteoporose). Pacientes com massa óssea reduzida receberam 2189 mg/kg de prednisona durante 13 anos e aqueles com osteoporose, 2510 mg/kg durante 14 anos. Estes valores, comparados com aqueles de pacientes com massa óssea normal, mostraram significância estatística (p=0,01). Não houve correlação significativa entre as demais variáveis analisadas e a DMO. Os marcadores 25(OH)D, PTH, CTx, P1NP e OC dos pacientes e controles não diferiram significativamente. Quando analisados em relação à doença e suas comorbidades, DMO e estatura final não apresentaram significação estatística. Conclusões: 1. Os valores de Zscore estatura inicial e final se correlacionaram fortemente com o alvo de estatura. 2. Não houve associação entre as características clinicas da doença e a aquisição do alvo de estatura, neste grupo de pacientes. 3. A massa óssea e os marcadores de mineralização dos pacientes não diferiram quando comparados aos controles. 4. Os 6 pacientes com massa óssea reduzida (2 com osteoporose) utilizaram dose total e tempo de uso da prednisona significativamente maior que aqueles com massa óssea adequada 5. Não houve correlação entre os níveis séricos dos marcadores de mineralização óssea e a doença e suas comorbidades, a estatura final e a DMO dos pacientes adultos com SN na infância e adolescência / Objectives: The aim of the present study was to evaluate the final height, bone mineral density (BMD) and bone mineralization markers of adults with steroid responsive Idiopathic Nephrotic Syndrome (NS) in childhood and adolescence and to examine the influence of the disease, its co-morbidities and the patients\' target height in the final height and mineralization results. Patients and Methods: We have analyzed initial and final anthropometric data of 60 patients (41 male and 19 females) and / or their records, with a minimum age of nineteen years or fully developed pubertal status (P4G4 in males and menarche in females). BMD (g/cm2) was evaluated in 26 patients and in 35 controls, with a concomitant analysis, of serum levels of 25-OH Vitamin D (25(OH)D), Parathyroid Hormone (PTH); C-terminal telopeptide of type I collagen (CTx) and aminoterminal propeptide of type 1 procollagen (P1NP) and Osteocalcin (OC) Results: Mean age at first consultation was 5.3 years (SD: 2.4 yrs) and at last consultation was 20.4 yrs (SD: 3.0 yrs). The mean cumulative dose of prednisone was 1254 mg/kg (SD: 831.39 mg/kg). The mean initial height SDS was -0.60; (SD: 1.0) the final height SDS was -0.64; (SD: 0.92), (t-test: p=0.72). The final height SDS showed correlated significantly only with the initial height SDS and the target height SDS. Six patients achieved a final height SDS <-2 and this finding showed a strong correlation to the initial height SDS and to the target height SDS in the male patients. The patients\' and control subjects L1L4 head of the femur and the total femur BMD and BMD SDS did not differ significantly. 6 patients and 2 control subjects showed a BMD SDS <-2 (low bone mass) while 2 patients and 1 control subjects showed a BMD SDS <-2.5 (osteoporosis). Patients with BMD SDS <-2 received 2189 mg / kg of prednisone over 13 years while those with a BMD SDS <-2.5 received 2510 mg / kg prednisone for 14 years (p = 0.01 vs BMD SDS -2 ). No other studied variable correlated significantly with BMD. The studied bone biomarkers showed similar results in patients and control subjects without a significant correlation with disease activity, co-morbidities, and BMD or height parameters. Conclusion: 1. the initial and final height SDS were strongly correlated to the height target. 2. INS and its co-morbidities did not prevent the patients to reach their target height 3. The patients\' BMD and bone mineralization markers did not differ when compared to controls. 4. The 6 patients with low bone mass (2 with osteoporosis) used a total dose of prednisone for a longer period of time in relation to those with an adequate BMD 5. There was no correlation between bone mineralization markers, disease activity and its co-morbidities, final height and BMD of adult patients with INS in childhood and adolescence

O objetivo deste trabalho foi avaliar a evolução clínica, sorológica e terapêutica dos doentes de pênfigo foliáceo, acompanhados no ambulatório de doenças bolhosas auto-Imunes do Departamento de Dermatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 1991 a 2002. Foram avaliados todos os 104 doentes com diagnóstico de pênfigo foliáceo acompanhados dentro do período citado. Os dados foram obtidos através das análises dos prontuários dos doentes. Do ponto de vista clínico, os doentes foram divididos de acordo com a forma clínica da doença: 15 doentes apresentaram a forma localizada da doença e 89, a forma generalizada de pênfigo foliáceo, sendo 12 eritrodérmicos. Com relação à terapêutica, a droga de escolha para tratamento do pênfigo foliáceo foi a prednisona oral usada como primeira opção em 99 doentes. A triancinolona foi opção terapêutica para 39 casos prednisona resistentes, sendo usada, ainda, em cinco casos como primeira opção. Os imunossupressores, em especial a ciclofosfamida, foram utilizados, com relativo sucesso, em casos de difícil controle. Houve queda dos títulos de auto-anticorpos circulantes da classe IgG após a instituição da terapêutica específica. As complicações mais freqüentes foram: parasitoses intestinais, infecções bacterianas e virais, diabetes e hipertensão. O índice de mortalidade foi de 5,7%, e esteve associado à septicemia e/ou à broncopneumonia. Cinco entre os seis doentes que evoluíram para óbito encontravam-se nos dois primeiros anos da doença. Seis mulheres engravidaram durante o seguimento e, dentre as oito gestações acompanhadas, três foram espontaneamente interrompidas e cinco culminaram com o nascimento de cinco crianças sadias. / The present study evaluated the clinical, serological and therapeutic profile of 104 patients with pemphigus foliaceus followed at Hospital das Clínicas, Department of Dermatology, University of São Paulo from 1991 to 2002. Data were obtained by retrospective analysis of patients´records . From the clinical point of view, 15 out of 104 pemphigus foliaceus patients presented the localized form, and 89 the generalized form; erythroderma was seen in 12 patients with the generalized form. The drug of choice for the treatment of pemphigus foliaceus was systemic prednisone, which was administered in 99 patients. Triamcinolone was utilized in 39 cases as an option for prednisone-resistant cases, and was utilized as a first option only in 5 patients. Immunossupressants, in special cyclophosphamide, were used as adjuvant therapy in refractory cases, and showed to be a good option. As for the patients´ serological profile, circulating IgG autoantibodies titers decreased after the introduction of specific therapy. Most frequent complications included: intestinal parasitosis, bacterial and viral infections, diabetes and hypertension. Mortality rate was 5.7%, occurred during the first two years of the disease, and was associated to sepsis or pneumonia. Six patients were pregnant during the follow-up: 5 out of 8 pregnancies were well-succeeded, resulting in five healthy newborns, and three were spontaneously interrupted.

Objetivos: Avaliar a estatura final, mineralização e marcadores de mineralização óssea de adultos com síndrome nefrótica (SN) idiopática corticossensível na infância e adolescência e analisar a influência da doença, suas comorbidades e do alvo de estatura no crescimento e mineralização destes pacientes. Casuística: Avaliamos a estatura final de 60 pacientes (41 masculinos e 19 femininos) com idade mínima de dezenove anos ou desenvolvimento genital P4G4 nos masculinos e menarca nos femininos portadores de SN corticossensível na infância e adolescência. Realizamos a densitometria óssea (DMO=g/cm2) em 26 destes pacientes e em 35 controles, com análise concomitante dos níveis séricos de 25 OH vitamina D3 (25(OH)D), Paratormônio (PTH), telopéptido carboxiterminal do colágeno tipo 1( (CTx), Propeptídeo Aminoterminal do Colágeno Tipo I (P1NP) e Osteocalcina (OC) Resultados: A idade média inicial dos 60 pacientes foi de 5a3m e final de 20a5m, com acompanhamento médio de 15a2m. A dose média de prednisona utilizada foi de 1264 mg/kg. O Zscore médio da estatura inicial (-0,60; SD: 1,0) e final (0,64; SD: 0,92), não diferiu significativamente (Teste T: p=0,72) entre si. O Zscore estatura na idade adulta se correlacionou significativamente apenas com o Zscore estatura inicial e com o Zscore alvo de estatura. Seis pacientes atingiram Zscore estatura < -2 na idade adulta e este achado demonstrou forte correlação com o Zscore estatura inicial e com o Zscore alvo de estatura. A DMO e Zscore DMO de L1L4, Cabeça do fêmur e do Fêmur total dos pacientes e controles não diferiram significativamente. 6 pacientes e 2 controles apresentaram Zscore DMO < -2 (massa óssea reduzida) enquanto 2 pacientes e 1 controle demonstraram , Zscore DMO < -2,5 (osteoporose). Pacientes com massa óssea reduzida receberam 2189 mg/kg de prednisona durante 13 anos e aqueles com osteoporose, 2510 mg/kg durante 14 anos. Estes valores, comparados com aqueles de pacientes com massa óssea normal, mostraram significância estatística (p=0,01). Não houve correlação significativa entre as demais variáveis analisadas e a DMO. Os marcadores 25(OH)D, PTH, CTx, P1NP e OC dos pacientes e controles não diferiram significativamente. Quando analisados em relação à doença e suas comorbidades, DMO e estatura final não apresentaram significação estatística. Conclusões: 1. Os valores de Zscore estatura inicial e final se correlacionaram fortemente com o alvo de estatura. 2. Não houve associação entre as características clinicas da doença e a aquisição do alvo de estatura, neste grupo de pacientes. 3. A massa óssea e os marcadores de mineralização dos pacientes não diferiram quando comparados aos controles. 4. Os 6 pacientes com massa óssea reduzida (2 com osteoporose) utilizaram dose total e tempo de uso da prednisona significativamente maior que aqueles com massa óssea adequada 5. Não houve correlação entre os níveis séricos dos marcadores de mineralização óssea e a doença e suas comorbidades, a estatura final e a DMO dos pacientes adultos com SN na infância e adolescência / Objectives: The aim of the present study was to evaluate the final height, bone mineral density (BMD) and bone mineralization markers of adults with steroid responsive Idiopathic Nephrotic Syndrome (NS) in childhood and adolescence and to examine the influence of the disease, its co-morbidities and the patients\' target height in the final height and mineralization results. Patients and Methods: We have analyzed initial and final anthropometric data of 60 patients (41 male and 19 females) and / or their records, with a minimum age of nineteen years or fully developed pubertal status (P4G4 in males and menarche in females). BMD (g/cm2) was evaluated in 26 patients and in 35 controls, with a concomitant analysis, of serum levels of 25-OH Vitamin D (25(OH)D), Parathyroid Hormone (PTH); C-terminal telopeptide of type I collagen (CTx) and aminoterminal propeptide of type 1 procollagen (P1NP) and Osteocalcin (OC) Results: Mean age at first consultation was 5.3 years (SD: 2.4 yrs) and at last consultation was 20.4 yrs (SD: 3.0 yrs). The mean cumulative dose of prednisone was 1254 mg/kg (SD: 831.39 mg/kg). The mean initial height SDS was -0.60; (SD: 1.0) the final height SDS was -0.64; (SD: 0.92), (t-test: p=0.72). The final height SDS showed correlated significantly only with the initial height SDS and the target height SDS. Six patients achieved a final height SDS <-2 and this finding showed a strong correlation to the initial height SDS and to the target height SDS in the male patients. The patients\' and control subjects L1L4 head of the femur and the total femur BMD and BMD SDS did not differ significantly. 6 patients and 2 control subjects showed a BMD SDS <-2 (low bone mass) while 2 patients and 1 control subjects showed a BMD SDS <-2.5 (osteoporosis). Patients with BMD SDS <-2 received 2189 mg / kg of prednisone over 13 years while those with a BMD SDS <-2.5 received 2510 mg / kg prednisone for 14 years (p = 0.01 vs BMD SDS -2 ). No other studied variable correlated significantly with BMD. The studied bone biomarkers showed similar results in patients and control subjects without a significant correlation with disease activity, co-morbidities, and BMD or height parameters. Conclusion: 1. the initial and final height SDS were strongly correlated to the height target. 2. INS and its co-morbidities did not prevent the patients to reach their target height 3. The patients\' BMD and bone mineralization markers did not differ when compared to controls. 4. The 6 patients with low bone mass (2 with osteoporosis) used a total dose of prednisone for a longer period of time in relation to those with an adequate BMD 5. There was no correlation between bone mineralization markers, disease activity and its co-morbidities, final height and BMD of adult patients with INS in childhood and adolescence

O objetivo deste trabalho foi avaliar a evolução clínica, sorológica e terapêutica dos doentes de pênfigo foliáceo, acompanhados no ambulatório de doenças bolhosas auto-Imunes do Departamento de Dermatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 1991 a 2002. Foram avaliados todos os 104 doentes com diagnóstico de pênfigo foliáceo acompanhados dentro do período citado. Os dados foram obtidos através das análises dos prontuários dos doentes. Do ponto de vista clínico, os doentes foram divididos de acordo com a forma clínica da doença: 15 doentes apresentaram a forma localizada da doença e 89, a forma generalizada de pênfigo foliáceo, sendo 12 eritrodérmicos. Com relação à terapêutica, a droga de escolha para tratamento do pênfigo foliáceo foi a prednisona oral usada como primeira opção em 99 doentes. A triancinolona foi opção terapêutica para 39 casos prednisona resistentes, sendo usada, ainda, em cinco casos como primeira opção. Os imunossupressores, em especial a ciclofosfamida, foram utilizados, com relativo sucesso, em casos de difícil controle. Houve queda dos títulos de auto-anticorpos circulantes da classe IgG após a instituição da terapêutica específica. As complicações mais freqüentes foram: parasitoses intestinais, infecções bacterianas e virais, diabetes e hipertensão. O índice de mortalidade foi de 5,7%, e esteve associado à septicemia e/ou à broncopneumonia. Cinco entre os seis doentes que evoluíram para óbito encontravam-se nos dois primeiros anos da doença. Seis mulheres engravidaram durante o seguimento e, dentre as oito gestações acompanhadas, três foram espontaneamente interrompidas e cinco culminaram com o nascimento de cinco crianças sadias. / The present study evaluated the clinical, serological and therapeutic profile of 104 patients with pemphigus foliaceus followed at Hospital das Clínicas, Department of Dermatology, University of São Paulo from 1991 to 2002. Data were obtained by retrospective analysis of patients´records . From the clinical point of view, 15 out of 104 pemphigus foliaceus patients presented the localized form, and 89 the generalized form; erythroderma was seen in 12 patients with the generalized form. The drug of choice for the treatment of pemphigus foliaceus was systemic prednisone, which was administered in 99 patients. Triamcinolone was utilized in 39 cases as an option for prednisone-resistant cases, and was utilized as a first option only in 5 patients. Immunossupressants, in special cyclophosphamide, were used as adjuvant therapy in refractory cases, and showed to be a good option. As for the patients´ serological profile, circulating IgG autoantibodies titers decreased after the introduction of specific therapy. Most frequent complications included: intestinal parasitosis, bacterial and viral infections, diabetes and hypertension. Mortality rate was 5.7%, occurred during the first two years of the disease, and was associated to sepsis or pneumonia. Six patients were pregnant during the follow-up: 5 out of 8 pregnancies were well-succeeded, resulting in five healthy newborns, and three were spontaneously interrupted.

No description available.

L’ostéonécrose (ON) et les fractures (FR) sont des complications qui prennent de plus en plus place dans le traitement pédiatrique de la leucémie aiguë lymphoblastique (LAL). L’ON peut être causée par différents facteurs, dont principalement l’utilisation de glucocorticoïdes. Les glucocorticoïdes sont administrés lors du traitement de la leucémie dans le but d’initier l’apoptose des cellules malignes tout en ayant un effet anti-inflammatoire. Cependant, l’utilisation de ces corticostéroïdes comprend des effets secondaires sérieux, notamment le développement d’ostéonécrose. Des variantes génétiques peuvent mettre certains patients plus à risque que d’autres. Plusieurs gènes ont déjà été signalés comme régulés par les actions glucocorticoïdes (GC). Les variations génétiques présentes dans les régions régulatrices de ces gènes peuvent affecter leur fonctionnement normal et, en fin de compte, de déterminer un risque accru de développer l’ON associé au traitement contre la leucémie. Pour cette raison, plusieurs polymorphismes ont été identifiés et étudiés dans la cohorte QcALL de Ste-Justine, concernant les gènes suivants : ABCB1, ACP1, BCL2L11, NFKB1, PARP1, et SHMT1. Ces gènes jouent majoritairement un rôle dans les mécanismes d’action des glucocorticoïdes, mais quelques-uns ont plutôt un effet direct sur le développement d’ostéonécrose. Nos recherches ont démontré une corrélation entre ces polymorphismes et l’apparition d’ostéonécrose chez les patients de la cohorte QcALL, traités aux glucocorticoïdes. L'incidence cumulative de l'ostéonécrose a été évaluée rétrospectivement chez 305 enfants atteints de la leucémie qui ont subi un traitement à l’hôpital Ste-Justine selon les protocoles DFCI de Boston (87-01, 91-01, 95-01 et 2000-01). Parmi les huit polymorphismes de BCL2L11 étudiés, les 891T> G (rs2241843) et 29201C> T (rs724710) ont été significativement associés à ON (p = 0.01 et p = 0.03, respectivement). L'association du polymorphisme 891T> G a été modulée par le type de corticostéroïde (CS), l’âge, le sexe et le groupe à risque (p ≤ 0,05). Le polymorphisme 29201C> T était particulièrement apparent chez les patients à haut risque (p = 0,003). La même étude était conduite en parallèle sur des patients de la cohorte DFCI de Boston (N = 192), et montrait des résultats significatifs pour les polymorphismes étudiés. En conclusion, les résultats de cette étude permettront de confirmer l’association de ces polymorphismes au développement d’ON chez les patients de LLA traités aux GC. / Osteonecrosis (ON) and fractures (FR) are complications that take place in the treatment of children acute lymphoblastic leukemia (cALL). They can be caused by various factors, mainly using glucocorticoids. The corticosteroids, dexamethasone (DXM) and prednisone (PDN) are administered during the treatment of leukemia to initiate apoptosis of malignant cells; while having an anti-inflammatory effect. However, the use of these corticosteroids has severe side effects, including the development of osteonecrosis. Moreover, some patients develop resistance to treatment, and are at risk of developing side effects. The genetic variants predispose some patients at higher risk than others. Several genes have been previously reported as up- or down regulated by the GCs actions. The genetic variations present in gene coding or regulatory regions can affect their function and ultimately determine an increased risk of developing ON associated to ALL therapy. Therefore, we investigated the association between several single nucleotide polymorphisms (SNPs) in six candidate genes: BCL2L11, NFKB1, PARP1, ABCB1, ACP1, and SHMT1. These genes play a role in the mechanisms of action of glucocorticoids, but some have more of a direct effect on the development of osteonecrosis. Our research has shown a correlation between these polymorphisms and the occurrence of osteonecrosis in patients in the QCALL cohort, treated with glucocorticoids. Cumulative incidence of osteonecrosis was assessed retrospectively in 305 children with ALL who underwent treatment with DFCI protocols (87-01, 91-01, 95-01 and 2000-01) in childhood ALL cohort from Quebec (QcALL). Among the eight tag BCL2L11 polymorphisms studied the 891T>G (rs2241843) and 29201C>T (rs724710) were significantly associated with ON (p = 0.01 and p = 0.03, respectively). Association of 891T>G polymorphism was modulated by type of corticosteroid (CS), age, sex and risk group (p ≤ 0.05 and that of 29201C>T was particularly apparent among high risk (p = 0.003) patients. These polymorphisms have shown significant ON association in several QcALL risk groups, mainly in corticosteroid groups, age < 10 years, and high risk (HR) group. Furthermore, the same study was conducted in parallel with patients in the replication (DFCI) cohort (N = 192), and we showed significant genetic association results for all studied polymorphisms. In conclusion, this study identifies that some ALL children have a high incidence of ON during the treatment that is highly associated with polymorphisms in different genes regulated by corticosteroids and ALL prognostic factors.