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1.
Cancer Genet ; 258-259: 85-92, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34666222

RESUMO

Osteosarcoma (OS) is a malignant bone tumor, with a peak of incidence in the second decade of life and possibly associated with the presence of germline mutations. Besides, clinicians have pointed to a second, rarer group of patients that develops OS before 10 years old. Here we access, through next-generation sequencing (NGS) strategy, the genetic alterations present in OS and blood samples from patients diagnosed before and during the second decade of life. A custom NGS panel, designed for the main alterations described in childhood and adolescence neoplasms, named Oncomine Childhood Cancer Research Assay (OCCRA©), was used. Of all 84 OS samples investigated, 42 (50%) presented some somatic variant, with TP53, MYC, CDK4, RB1 and PDGFRA genes harboring the most observed genetic variants. MYC CNVs were more frequent in tumors from patients diagnosed before 10 years old (X21= 5.18, p = 0.023). Additionally, patients diagnosed during the second decade of life presented a higher percentage of somatic and germline variants. Germline variants in TP53 and RB1 were found in 5 of the 11 (45.5%) patients analyzed. Clinical variables and tumor histopathological characteristics were also collected and correlated with our molecular findings.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/patologia , Variações do Número de Cópias de DNA , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Osteossarcoma/patologia , Adolescente , Neoplasias Ósseas/genética , Criança , Feminino , Seguimentos , Humanos , Masculino , Osteossarcoma/genética , Prognóstico
2.
Neuroimage ; 142: 351-370, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27521745

RESUMO

Although different MRI-based techniques have been proposed to assess the hemispheric lateralization for language (HLL), the agreement across methods, and its relationship with language abilities, are still a matter of debate. In the present study we obtained measures of HLL using both task-evoked activity during the execution of three different protocols and task-free methods of functional [resting state functional connectivity (rs-FC)] and anatomical [diffusion tensor imaging (DTI) tractography] connectivity. Regional analyses focusing on the perisylvian language network were conducted to assess the consistency of HLL across techniques. In addition, following a multimodal approach, we identified macro-factors of lateralization and examined their relationship with language performance. Our findings indicate the existence of a negative relationship between the structural asymmetry of the direct segment of the arcuate fasciculus (AF) and the inter-hemispheric rs-FC of key nodes of the perisylvian network. Instead, despite all the language tasks exhibited a leftward pattern of asymmetry, measures of HLL derived from task-evoked activity did not show a direct relationship with those obtained with the two task-free methods. Furthermore, a robust brain-behavioral relationship was observed only with a specific macro-factor that combined HLL measures derived from all MRI techniques. In particular, general language performance was positively related to more symmetrical structural organization, stronger inter-hemispheric communication at rest but more lateralized activation of Wernicke's territory during production tasks. Our findings, while not supporting the existence of a direct relationship between indices of hemispheric lateralization for language derived from different MRI techniques, indicate that general language performance can be indexed using combined MRI measures. The same approach might prove successful for likewise complex human behaviours.


Assuntos
Encéfalo , Conectoma/métodos , Lateralidade Funcional/fisiologia , Idioma , Imageamento por Ressonância Magnética/métodos , Adulto , Comportamento/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Compreensão/fisiologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Adulto Jovem
3.
Oncogene ; 35(5): 537-48, 2016 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-25893302

RESUMO

Merlin (Moesin-ezrin-radixin-like protein, also known as schwannomin) is a tumor suppressor protein encoded by the neurofibromatosis type 2 gene NF2. Loss of function mutations or deletions in NF2 cause neurofibromatosis type 2 (NF2), a multiple tumor forming disease of the nervous system. NF2 is characterized by the development of bilateral vestibular schwannomas. Patients with NF2 can also develop schwannomas on other cranial and peripheral nerves, as well as meningiomas and ependymomas. The only potential treatment is surgery/radiosurgery, which often results in loss of function of the involved nerve. There is an urgent need for chemotherapies that slow or eliminate tumors and prevent their formation in NF2 patients. Interestingly NF2 mutations and merlin inactivation also occur in spontaneous schwannomas and meningiomas, as well as other types of cancer including mesothelioma, glioma multiforme, breast, colorectal, skin, clear cell renal cell carcinoma, hepatic and prostate cancer. Except for malignant mesotheliomas, the role of NF2 mutation or inactivation has not received much attention in cancer, and NF2 might be relevant for prognosis and future chemotherapeutic approaches. This review discusses the influence of merlin loss of function in NF2-related tumors and common human cancers. We also discuss the NF2 gene status and merlin signaling pathways affected in the different tumor types and the molecular mechanisms that lead to tumorigenesis, progression and pharmacological resistance.


Assuntos
Neoplasias/metabolismo , Neurofibromina 2/metabolismo , Animais , Humanos , Neoplasias/genética , Neurofibromina 2/genética
4.
Oncogene ; 33(27): 3571-82, 2014 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-23934191

RESUMO

Neurofibromatosis type 2 (NF2) is caused by mutations in the NF2 gene that encodes a tumor-suppressor protein called merlin. NF2 is characterized by formation of multiple schwannomas, meningiomas and ependymomas. Merlin loss-of-function is associated with increased activity of Rac and p21-activated kinases (PAKs) and deregulation of cytoskeletal organization. LIM domain kinases (LIMK1 and 2) are substrate for Cdc42/Rac-PAK and modulate actin dynamics by phosphorylating cofilin at serine-3. This modification inactivates the actin severing and depolymerizing activity of cofilin. LIMKs also translocate into the nucleus and regulate cell cycle progression. Significantly, LIMKs are overexpressed in several tumor types, including skin, breast, lung, liver and prostate. Here we report that mouse Schwann cells (MSCs) in which merlin function is lost as a result of Nf2 exon2 deletion (Nf2(ΔEx2)) exhibited increased levels of LIMK1, LIMK2 and active phospho-Thr508/505-LIMK1/2, as well as phospho-Ser3-cofilin, compared with wild-type normal MSCs. Similarly, levels of LIMK1 and 2 total protein and active phosphorylated forms were elevated in human vestibular schwannomas compared with normal human Schwann cells (SCs). Reintroduction of wild-type NF2 into Nf2(ΔEx2) MSC reduced LIMK1 and LIMK2 levels. We show that pharmacological inhibition of LIMK with BMS-5 decreased the viability of Nf2(ΔEx2) MSCs in a dose-dependent manner, but did not affect viability of control MSCs. Similarly, LIMK knockdown decreased viability of Nf2(ΔEx2) MSCs. The decreased viability of Nf2(ΔEx2) MSCs was not due to caspase-dependent or -independent apoptosis, but rather due to inhibition of cell cycle progression as evidenced by accumulation of cells in G2/M phase. Inhibition of LIMKs arrests cells in early mitosis by decreasing aurora A activation. Our results suggest that LIMKs are potential drug targets for NF2 and tumors associated with merlin deficiency.


Assuntos
Quinases Lim/metabolismo , Terapia de Alvo Molecular , Neurofibromatose 2/tratamento farmacológico , Neurofibromatose 2/enzimologia , Inibidores de Proteínas Quinases/farmacologia , Fatores de Despolimerização de Actina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Aurora Quinase A/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Inativação Gênica , Humanos , Quinases Lim/antagonistas & inibidores , Quinases Lim/deficiência , Quinases Lim/genética , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Camundongos , Mitose/efeitos dos fármacos , Neurofibromatose 2/metabolismo , Neurofibromatose 2/patologia , Neurofibromina 2/genética , Neurofibromina 2/metabolismo , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Células de Schwann/citologia , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Células de Schwann/patologia
5.
J Pediatr (Rio J) ; 88(1): 87-92, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22344501

RESUMO

OBJECTIVE: To perform a comparative assessment of the clinical and epidemiological aspects of testicular tumors in childhood and adolescence. METHODS: Retrospective analysis of medical records of patients with testicular or paratesticular neoplasms. Patients under 10 years were classified as children and patients between 10 and 20 were classified as adolescents. The obtained results were compared through the two-sample test for proportions: non-parametric Mann-Whitney test and log-rank test. RESULTS: 60 patients were admitted in the period from January 1992 to July 2009: 34 children and 26 adolescents with testicular or paratesticular neoplasms. The main manifestations were testicular tumor and scrotal pain. Pain complaints were more common in adolescents (p = 0.006), who presented a mean time from disease onset to diagnosis of 4.9 months, longer than children, who presented a period of 2.3 months from disease onset to diagnosis (p = 0.01). Histological types were as follows: germ cell tumors in 32/60 (53%), rhabdomyosarcomas (RMSs) in 23/60 (38.3%), and other in 5/60 (8.3%). Adolescents presented a higher incidence of RMSs, lymph node metastases (p = 0.003) and distant metastases (p = 0.035). Differences in survival rates among the studied patients were not statistically significant, the only indicative being that survival in RMS cases is longer for children (p = 0.072). CONCLUSIONS: Compared to children, adolescents with testicular tumor presented longer time from disease onset to diagnosis, aggressive histological type and advanced illness at diagnosis, despite the small sample analyzed.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Dor Aguda/etiologia , Adolescente , Distribuição por Idade , Brasil/epidemiologia , Criança , Métodos Epidemiológicos , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/patologia , Rabdomiossarcoma/complicações , Rabdomiossarcoma/epidemiologia , Rabdomiossarcoma/patologia , Escroto , Taxa de Sobrevida , Neoplasias Testiculares/complicações , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/patologia , Fatores de Tempo , Adulto Jovem
6.
J. pediatr. (Rio J.) ; 88(1): 87-92, jan.-fev. 2012. ilus, graf
Artigo em Português | LILACS | ID: lil-617055

RESUMO

OBJETIVO: Avaliar comparativamente aspectos clínicos e epidemiológicos dos tumores de testículo na infância e adolescência. MÉTODOS: Análise retrospectiva dos prontuários de pacientes com neoplasias de testículo ou paratesticulares. Foram classificados como crianças os menores de 10 anos e como adolescentes os pacientes entre 10 e 20 anos. Os resultados obtidos foram comparados por meio do teste para duas proporções: teste não paramétrico de Mann-Whitney e teste de log-rank. RESULTADOS: No período de janeiro de 1992 a julho de 2009, foram admitidos 60 pacientes: 34 crianças e 26 adolescentes com neoplasias de testículo ou paratesticulares. As principais manifestações foram tumor e dor na bolsa escrotal. A queixa de dor foi mais comum em adolescentes (p = 0,006). Estes apresentaram tempo médio de história de 4,9 meses, mais prolongado do que crianças, com 2,3 meses (p = 0,01). Os tipos histológicos encontrados foram: tumores de células germinativas em 32/60 (53 por cento), rabdomiossarcomas (RMSs) em 23/60 (38,3 por cento) e outros em 5/60 (8,3 por cento). Os adolescentes apresentaram maior frequência de RMSs, metástases em linfonodos (p = 0,003) e a distância (p = 0,035). As diferenças na sobrevida dos pacientes estudados não foram estatisticamente significantes, havendo apenas indicativo de que a sobrevida, nos casos de RMS, é maior nas crianças (p = 0,072). CONCLUSÕES: Os adolescentes com tumor testicular apresentaram maior tempo de história, tipo histológico agressivo e doença avançada ao diagnóstico quando comparados às crianças, a despeito da pequena amostra.


OBJECTIVE: To perform a comparative assessment of the clinical and epidemiological aspects of testicular tumors in childhood and adolescence. METHODS: Retrospective analysis of medical records of patients with testicular or paratesticular neoplasms. Patients under 10 years were classified as children and patients between 10 and 20 were classified as adolescents. The obtained results were compared through the two-sample test for proportions: non-parametric Mann-Whitney test and log-rank test. RESULTS: 60 patients were admitted in the period from January 1992 to July 2009: 34 children and 26 adolescents with testicular or paratesticular neoplasms. The main manifestations were testicular tumor and scrotal pain. Pain complaints were more common in adolescents (p = 0.006), who presented a mean time from disease onset to diagnosis of 4.9 months, longer than children, who presented a period of 2.3 months from disease onset to diagnosis (p = 0.01). Histological types were as follows: germ cell tumors in 32/60 (53 percent), rhabdomyosarcomas (RMSs) in 23/60 (38.3 percent), and other in 5/60 (8.3 percent). Adolescents presented a higher incidence of RMSs, lymph node metastases (p = 0.003) and distant metastases (p = 0.035). Differences in survival rates among the studied patients were not statistically significant, the only indicative being that survival in RMS cases is longer for children (p = 0.072). CONCLUSIONS: Compared to children, adolescents with testicular tumor presented longer time from disease onset to diagnosis, aggressive histological type and advanced illness at diagnosis, despite the small sample analyzed.


Assuntos
Adolescente , Criança , Humanos , Masculino , Adulto Jovem , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Distribuição por Idade , Dor Aguda/etiologia , Brasil/epidemiologia , Métodos Epidemiológicos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/patologia , Rabdomiossarcoma/complicações , Rabdomiossarcoma/epidemiologia , Rabdomiossarcoma/patologia , Escroto , Taxa de Sobrevida , Fatores de Tempo , Neoplasias Testiculares/complicações , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/patologia
7.
J Clin Oncol ; 24(7): 1161-8, 2006 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-16505436

RESUMO

PURPOSE: To evaluate the impact of chemotherapy and surgery on the outcome of osteosarcoma (OS) of the extremities and to identify prognostic factors in Brazilian patients. PATIENTS AND METHODS: A total of 225 patients with metastatic and nonmetastatic OS of the extremities were enrolled and assessed in two consecutive studies designed and implemented by the Brazilian Osteosarcoma Treatment Group. RESULTS: The 5-year survival and event-free survival rates for the 209 assessable patients were 50.1% and 39%, respectively; for the 178 patients with nonmetastatic disease at diagnosis, the rates were 60.5% and 45.5%, respectively. The multivariate analysis showed that the following variables were associated with a shorter survival: metastases at diagnosis (P < .001), necrosis grades 1 and 2 (P = .046), and tumor size (P = .0071). CONCLUSION: The overall 5- and 10-year survival rates were lower than the rates reported in North American and European trials. A pattern of advanced disease at diagnosis was often present, with a high proportion of patients having metastases (20.8%) and large tumor size (42.9%). However, these features were not necessarily associated with longer duration of prediagnostic symptoms. These findings were considered in the strategic planning of the current Brazilian cooperative study, with the aim of improving survival and quality of life of a large number of patients with OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Procedimentos Ortopédicos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/cirurgia , Adolescente , Amputação Cirúrgica , Neoplasias Ósseas/patologia , Brasil , Carboplatina/administração & dosagem , Quimioterapia Adjuvante , Criança , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Salvamento de Membro , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Metotrexato/administração & dosagem , Análise Multivariada , Procedimentos Ortopédicos/métodos , Osteossarcoma/secundário , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
8.
Support Care Cancer ; 11(6): 356-61, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12720070

RESUMO

The resource utilization and cost of 51 episodes of febrile neutropenia in children with leukemia and lymphomas who were admitted to the Pediatric Oncology Institute (GRAAC) of the Federal University of São Paulo were analyzed. Patients aged 60 days to 21 years with confirmed diagnoses of acute myeloid leukemia, acute lymphoid leukemia, non-Hodgkin lymphoma, or Hodgkins disease who presented axillary temperature above 38 degrees C at least once episode, or between 37.5 degrees C and 38 degrees C on three occasions during a 24-h period, neutrophil count below 500/mm(3), or between 500/mm(3)and 1,000/mm(3) but expected to fall below 500/mm(3) were included in the study. The patients' ages varied between 1 and 15.6 years, and 67% of the patients were male. The median cost per treated episode was US dollars 2,660 (2,039). Hospitalization costs accounted for 62% of the total cost of the treatment, antibacterials accounting for 23%. Episodes in patients with documented infections had a higher median direct cost than episodes in patients with fever of unknown origin (P=0.018). There was a trend for a higher median direct cost in episodes among patients with a worse prognostic factor, such as type of underlying disease, presence of documented infection, and longer duration of neutropenia. This is the first study to evaluate the economics of febrile neutropenia episodes in Brazil, and serves as a basis for resource utilization and costs incurred in the treatment of such patients in this country.


Assuntos
Febre/economia , Febre/terapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Serviços de Saúde/estatística & dados numéricos , Leucemia/complicações , Linfoma/complicações , Neutropenia/economia , Neutropenia/terapia , Adolescente , Adulto , Brasil , Criança , Pré-Escolar , Custos e Análise de Custo , Feminino , Febre/etiologia , Humanos , Lactente , Masculino , Neutropenia/etiologia , Prognóstico
9.
J Pediatr Surg ; 36(10): 1581-3, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11584414

RESUMO

Duplications of the alimentary tract are rare malformations. A case of a 2-year-old girl with an intestinal intussusception caused by a cystic duplication of the cecum is presented. This case report is justified by its clinical features and the difficult diagnosis, which was only confirmed during surgery. Ultrasonography had documented an abdominal mass that then disappeared and later reappeared, leading to surgical indication. During surgery, the intussusception within the abdomen was reduced, and right hemicolectomy was performed around the mass in the interior part of the cecum and appendix, with ileocolic anastomosis. On resecting the cecum, a cystic duplication measuring 4 x 3 cm was observed, with a granular mucous layer, an ulcerated hole in its interior, and inflammatory reaction. The patient had an uneventful recovery and was discharged on the fourth postoperative day.


Assuntos
Ceco/anormalidades , Doenças do Íleo/etiologia , Intussuscepção/etiologia , Pré-Escolar , Feminino , Humanos , Doenças do Íleo/cirurgia , Intussuscepção/cirurgia
10.
Cancer Genet Cytogenet ; 130(1): 14-21, 2001 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-11672768

RESUMO

Osteosarcomas (OS) are aggressive tumors of the bone and often have a poor prognosis. Conventional cytogenetic analyses of OS have revealed highly complex karyotypes, with numerous abnormalities. In this study, we analyzed 18 untreated OS tumors from 17 patients of the younger incidence age group by comparative genomic hybridization (CGH), 4 tumors by spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Comparative genomic hybridization identified frequent copy number changes of the chromosomal region 1p (10/17) and gain of part or all of chromosome 19(8/17). In addition gains were observed at 5p(3/17), 8q(3/17), 16p(3/17), and 17p(5/17); and losses at chromosomes 2q(3/17), 10(4/17) and 13(3/17). High level gains were detected in the 8q23 approximately q24 region in two tumors as well as at 17p in one primary and a metastatic tumor. Minimal regions of gain were present at 1p35 approximately p36.3 (8/17); 5p14 approximately p15.2 (3/17), and 8q22 approximately q24.3 (3/17). SKY analysis demonstrated that OS has a complex pattern of clonal and non-clonal rearrangements and helped confirm the structural basis for the imbalances detected by CGH. Spectral karyotyping confirmed an overall pattern of chromosomal gain affecting 1p in all four tumors. Fluorescence in situ hybridization analysis from these tumors confirmed the gain of the 1p36 region in 2 tumors as determined by CGH analysis as well as the amplification of 8q.


Assuntos
Neoplasias Ósseas/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 1 , Hibridização de Ácido Nucleico , Osteossarcoma/genética , Genoma , Humanos , Hibridização in Situ Fluorescente , Cariotipagem
11.
Minerva Cardioangiol ; 49(2): 99-106, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11292953

RESUMO

BACKGROUND: Hypertensive patients with left ventricular hypertrophy and normal systolic function can develop congestive heart failure refractory to conventional drug therapy with digoxin, diuretic, and vasodilators. METHODS: We studied 8 patients with a history of systemic hypertension (6 females and 2 males, mean age 69+/-6 years), affected by New York Heart Association (NYHA) class IV congestive heart failure notwithstanding conventional drug therapy with digoxin, diuretic, and vasodilators. After clinical history and physical examination, blood chemistry including cardiac enzymes, arterial blood gases, chest roentgenogram, standard 12-lead ECG, and complete echocardiographic study were performed in all patients. RESULTS: In all cases, a left ventricle with increased wall thickness, normal cavity size, and normal or supernormal systolic function was shown. All patients had left ventricular systolic dynamic obstruction, with peak gradient between 36 and 130 mmHg (mean 83+/-31). After having stopped treatment with nitrates, digoxin, and diuretics, drug therapy with calcium channel antagonists or beta-blockers was started, and rapid clinical improvement with disappearance of left ventricular outflow obstruction was observed. CONCLUSIONS: Sometimes, a distinction between several forms of heart failure is clinically impossible. However, when conventional therapy is not effective in patients with longstanding history of systemic hypertension and ECG signs of left ventricular hypertrophy, diastolic heart failure and/or dynamic left ventricular obstruction should be suspected. Thus, an early echocardiographic study should be performed.


Assuntos
Insuficiência Cardíaca/etiologia , Hipertensão/complicações , Obstrução do Fluxo Ventricular Externo/complicações , Idoso , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Sístole , Obstrução do Fluxo Ventricular Externo/fisiopatologia
12.
Minerva Cardioangiol ; 49(2): 127-30, 2001 Apr.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-11292956

RESUMO

A 60-year-old woman with systemic sclerosis, systemic hypertension, and chronic renal failure, presented with clinical manifestations of heart failure. An echocardiogram showed a mildly dilated left ventricle and global hypokinesis. A six-month treatment including reduced sodium intake, furosemide, and nifedipine did not change the clinical and instrumental findings. Casually, vitamin E (600 mg daily) was added. After 6 months, clinical manifestations of heart failure were disappeared and the echocardiogram showed a normally-sized left ventricle with normal wall motion.


Assuntos
Antioxidantes/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Escleroderma Sistêmico/complicações , Vitamina E/uso terapêutico , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Pessoa de Meia-Idade , Indução de Remissão
13.
Pediatr Surg Int ; 16(7): 529-32, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11057562

RESUMO

We review our experience and the literature in treating 4 patients with Wilms' tumor (WT) with intracardiac extension among 92 patients with this neoplasm. Cardiopulmonary bypass with circulatory arrest and profound hypothermia was used. There were 3 boys (3 years, 4 years 5 months, and 15 years) and 1 girl (6 years). The follow-up periods were 8 months, 3 years, 2 years 6 months, and 15 years, respectively. We had no surgical complications and conclude that the preoperative diagnosis is extremely important. These patients must be transferred to institutions where concomitant cardiac procedures can be performed. In treating patients with WT, Doppler ultrasound must be used preoperatively in all cases, not only those in which clinical and radiologic signs of intravascular involvement are found. We propose that preoperative chemotherapy should be used, as it shrinks the thrombus and causes desirable adherence of the thrombus to the venous wall, reducing the probability of thromboembolism during the surgical procedure. We also find this method safer than in our 1st case, where neither cardiac arrest nor hypothermia was used. Our results agree with the literature that intracardiac extension of WT does not worsen its prognosis when a rational surgical approach is used.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Neoplasias Cardíacas/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Tumor de Wilms/cirurgia , Adolescente , Ponte Cardiopulmonar , Criança , Pré-Escolar , Feminino , Parada Cardíaca Induzida , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/etiologia , Humanos , Hipotermia Induzida , Neoplasias Renais/complicações , Neoplasias Renais/tratamento farmacológico , Masculino , Terapia Neoadjuvante , Resultado do Tratamento , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgia , Tumor de Wilms/complicações , Tumor de Wilms/tratamento farmacológico
14.
Clin Orthop Relat Res ; (373): 32-8, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10810460

RESUMO

Fourteen boys (56%) and 11 girls (44%) 4 to 17 years of age (mean, 12.2 years) who had osteosarcoma and open epiphyseal plates were studied. A possible correlation between transepiphyseal spread of osteosarcoma and radiologic and histopathologic findings was investigated. Epiphyseal plate invasion was detected radiologically in only 11 patients (44%), whereas histopathologic examination showed transepiphyseal extension in 21 patients (84%). The authors conclude that the epiphyseal plate is not a barrier against tumor growth and strongly recommend that limb salvage surgery preserving the epiphysis be planned carefully.


Assuntos
Neoplasias Ósseas/patologia , Lâmina de Crescimento/patologia , Osteossarcoma/patologia , Adolescente , Neoplasias Ósseas/cirurgia , Criança , Pré-Escolar , Feminino , Lâmina de Crescimento/cirurgia , Humanos , Masculino , Invasividade Neoplásica , Osteossarcoma/cirurgia , Prognóstico
15.
Med Pediatr Oncol ; 34(2): 87-91, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10657866

RESUMO

BACKGROUND: Infections are one of the major complications in children undergoing chemotherapy. Monotherapy with either ciprofloxacin or ceftriaxone is safe and efficient in low-risk patients (solid tumors and stage I/II lymphomas). The same drugs may be used in an outpatient setting, decreasing costs and the risk of nosocomial infections. PROCEDURE: Low-risk patients (N = 70) with episodes of fever and neutropenia (N = 116) were randomized to receive either oral ciprofloxacin or intravenous ceftriaxone as outpatients. Only one patient had a central venous catheter. RESULTS: Episodes of fever and neutropenia were classified as fever of unknown origin (41% vs. 32%) or clinically documented infection (56% vs. 63%) in the ciprofloxacin and ceftriaxone groups, respectively. Most of these infections were of upper respiratory tract, skin, or gastrointestinal origin. The mean duration of neutropenia was 5 vs. 6 days. Fever persisted for 1-9 days (mean 2 vs. 3 days). Therapy was successful with no modifications in 83% vs. 75% of the episodes. Patients were admitted in 7% vs. 4% of the episodes. No bone or joint side effects were seen in either group. All patients survived. CONCLUSIONS: Outpatient therapy with either oral ciprofloxacin or intravenous ceftriaxone for fever and neutropenia is effective and safe in pediatric patients with solid tumors and stage I/II non-Hodgkin lymphoma (low-risk patients).


Assuntos
Anti-Infecciosos/administração & dosagem , Antineoplásicos/efeitos adversos , Ceftriaxona/administração & dosagem , Cefalosporinas/administração & dosagem , Ciprofloxacina/administração & dosagem , Febre/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neutropenia/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Assistência Ambulatorial , Criança , Pré-Escolar , Febre/induzido quimicamente , Humanos , Neutropenia/induzido quimicamente , Estudos Prospectivos , Fatores de Risco
16.
Med Pediatr Oncol ; 33(2): 71-5, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10398179

RESUMO

BACKGROUND: Chemotherapy has dramatically improved the rates of cure and survival of patients with localized and metastatic osteosarcoma. Nonetheless, the number of chemotherapeutic agents active against osteosarcoma is limited to doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide. Carboplatin, a cisplatin analogue, has been tested as a single agent in patients with recurrent osteosarcoma or as part of multiagent chemotherapy in newly diagnosed patients. PROCEDURE: We tested the activity and toxicity of two cycles of intraarterial carboplatin as a "window therapy" (600 mg/m2 per cycle) in 33 consecutive patients with extremity osteosarcoma before the start of multiagent chemotherapy. Response was based on clinical (tumor diameter, local inflammatory signs, and range of motion) and radiological parameters (plain local films and arteriographic studies prior to drug administration). RESULTS: Patients' age ranged between 8 and 18 years (median age 13 years). Primary tumor originated from the femur (15 patients), tibia (10 patients), fibula (4 patients), humerus (3 patients), and calcaneus (1 patient). Only 7 patients (21%) had metastatic disease at diagnosis (5 in the lung and 2 in other bones). A favorable clinical and radiological response was documented in 81% and 73% of the patients, respectively. Clinical and radiological progression occurred in 12% and 9% of the patients, respectively. Seventeen of the patients remain alive and disease-free. Survival and event-free survival at 3 years for nonmetastatic patients are 71% (SE = 9%) and 65% (SE = 9%), respectively; for metastatic patients, the figures are 17% (SE = 15%) and 14% (SE = 13%), respectively. CONCLUSIONS: We conclude that carboplatin is an active agent in the treatment of newly diagnosed extremity osteosarcoma.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Carboplatina/administração & dosagem , Osteossarcoma/tratamento farmacológico , Adolescente , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Carboplatina/uso terapêutico , Quimioterapia Adjuvante , Criança , Extremidades , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/secundário , Radiografia , Análise de Sobrevida
17.
Med Pediatr Oncol ; 30(3): 183-6, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9434830

RESUMO

This, the fifth official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, develops another important topic: the Therapeutic Alliance between families and staff. This is addressed to the Pediatric Oncology Community as Guidelines that could be followed. Every parent, medical staff member, and psychosocial professional involved in the care of the child should be responsible for cooperating in the child's best interest. Everyone must work together toward the common goal of curing the cancer and minimizing its medical and psychosocial side-effects.


Assuntos
Família , Neoplasias/psicologia , Equipe de Assistência ao Paciente , Apoio Social , Humanos , Neoplasias/terapia , Pediatria
18.
J Am Coll Dent ; 65(4): 46-8, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9929990

RESUMO

This essay defines managed care and presents three particular ways it affects the profession of dentistry. The first issue is whether managed care is needed in dentistry; the second is the effects of managed care on treatment; and finally the dentist-patient relationship is examined. It is incumbent on dental students to be highly proficient in understanding and managing managed care because of the potential this system has for vast impact on patients, the profession, and one's practice.


Assuntos
Ética Odontológica , Programas de Assistência Gerenciada , Relações Dentista-Paciente , Humanos , Administração da Prática Odontológica/economia , Estudantes de Odontologia/psicologia , Estados Unidos
19.
Rev. bras. cancerol ; 43(3): 191-203, jul.-set. 1997. tab, graf
Artigo em Português | LILACS | ID: lil-199508

RESUMO

O câncer representa hoje a primeira causa de morte por doença entre a populaçÝo de faixa etária compreendida entre 1 e 21 anos nos Estados Unidos e em outros países economicamente desenvolvidos. No Brasil, esta doença figura como a terceira causa de morte por doença entre a populaçäo de faixa etária compreendida entre 1 e 14 anos, sendo já a primeira causa de óbito no município e no estado de Säo Paulo no grupo etário compreendido entre 5 e 14 anos, excluindo-se acidentes e causas externas. O objetivo deste artigo é informar a classe médica, principalmente a pediátrica, das particularidades do câncer infantil e de suas diferenças com as formas dos adultos, mais conhecidas e freqüentes. Graças à moderna abordagem multidisciplinar, o câncer infantil pode atingir índices de cura de 60 porcento a 70 porcento, mas, para tal, é imprescindível o diagnóstico precoce. Portanto, é importante que toda a comunidade pediátrica mostre-se motivada e informada sobre os sinais e sintomas das neoplasias pediátricas, já que näo dispomos de métodos de "screening" täo úteis e eficazes como para o controle do câncer do adulto.


Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/mortalidade , Neoplasias/prevenção & controle , Neoplasias/terapia , Oncogenes , Pediatria , Taxa de Sobrevida , Brasil , Estados Unidos
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