RESUMO
PURPOSE: Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis and pachydermia with defects in the degradation of prostaglandin E2 (PGE2). Mutations in SLCO2A1 gene-encoding prostaglandin transporter (PGT) resulted in PHO, autosomal recessive 2 (PHOAR2). The spectrum of mutations and variable clinical complications of PHOAR2 has been delineated. In this study, we investigated a Chinese PHO family with a manifestation of Bartter-like hypokalemia. METHODS: Clinical manifestations were collected and genetic analyses were performed in the PHO family. RESULTS: The 33-year-old male proband had severe hypokalemia due to potassium loss from the kidney, while his brother had mild hypokalemia. After being treated with etoricoxib, the serum potassium level of the patient increased rapidly to the normal range which corresponded with the reduction in his serum PGE2 and PE2 metabolite (PGEM) levels. A novel SLCO2A1 compound heterozygous mutation of p.I284V and p.C459R was identified in two PHO patients in this family. CONCLUSIONS: The present findings supported that the Bartter-like hypokalemia is a new complication of PHOAR2 caused by the high level of PGE2. Etoricoxib was demonstrated to be effective for the renal hypokalemia in PHO patients.
Assuntos
Síndrome de Bartter/genética , Hipopotassemia/genética , Mutação de Sentido Incorreto , Transportadores de Ânions Orgânicos/genética , Osteoartropatia Hipertrófica Primária/genética , Adulto , Povo Asiático/genética , Síndrome de Bartter/complicações , China , Análise Mutacional de DNA , Família , Heterozigoto , Humanos , Hipopotassemia/etiologia , Masculino , Osteoartropatia Hipertrófica Primária/complicações , LinhagemRESUMO
Objectives. To analyse the lung metastasis and possible factors influencing lung metastasis in alveolar soft part sarcoma (ASPS) patients. Methods. The medical records of 64 consecutive ASPS patients were reviewed to analyse their treatments, features of lung metastasis, and possible factors influencing lung metastasis. Results. Thirty-six females and 28 males with a median age of 27 years were included. The primary disease sites were the extremities in 51 patients and other locations in 13 patients. The median primary tumour size was 5 cm. Wide local excision of the primary tumour was performed on 56 patients (87.5 %). Thirteen patients (20.3 %) received postoperative adjuvant radiotherapy, and nine patients (14.1 %) underwent adjuvant chemotherapy. Twelve patients (18.8 %) presented with metastatic lung disease. Twenty-nine patients (45.3 %) developed metastatic lung disease during follow-up. Lung metastasis occurred in 64.1 % of the patients. Lung metastasis was detected at a median interval of 20 months after primary ASPS diagnosis. Being male, >20 years of age, having a primary tumour size ≥5 cm, and local recurrence were associated with a greater rate of lung metastasis. Median survival after the diagnosis of lung metastasis was 34 months. The 5-year survival rates were 64.1 and 95.2 % for patients with and without lung metastasis (P < 0.001). Thirty-seven patients with metastatic lung disease received anthracycline- and ifosfamide-based chemotherapy. One patient experienced a partial remission. Conclusions. ASPS patients have a high prevalence of lung metastasis. Sex, age, primary tumour size, and local recurrence are major factors influencing lung metastasis. Chemotherapy is not efficacious in ASPS patients with lung metastasis (AU)
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Assuntos
Adulto , Feminino , Humanos , Masculino , Neoplasias Pulmonares/diagnóstico , Sarcoma Alveolar de Partes Moles/complicações , Sarcoma Alveolar de Partes Moles/diagnóstico , Sarcoma Alveolar de Partes Moles/tratamento farmacológico , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/fisiopatologia , Sarcoma Alveolar de Partes Moles/fisiopatologia , Quimioterapia Adjuvante/instrumentação , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante , Radioterapia Adjuvante/instrumentação , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante , Quimiorradioterapia Adjuvante/métodosRESUMO
OBJECTIVES: To analyse the lung metastasis and possible factors influencing lung metastasis in alveolar soft part sarcoma (ASPS) patients. METHODS: The medical records of 64 consecutive ASPS patients were reviewed to analyse their treatments, features of lung metastasis, and possible factors influencing lung metastasis. RESULTS: Thirty-six females and 28 males with a median age of 27 years were included. The primary disease sites were the extremities in 51 patients and other locations in 13 patients. The median primary tumour size was 5 cm. Wide local excision of the primary tumour was performed on 56 patients (87.5 %). Thirteen patients (20.3 %) received postoperative adjuvant radiotherapy, and nine patients (14.1 %) underwent adjuvant chemotherapy. Twelve patients (18.8 %) presented with metastatic lung disease. Twenty-nine patients (45.3 %) developed metastatic lung disease during follow-up. Lung metastasis occurred in 64.1 % of the patients. Lung metastasis was detected at a median interval of 20 months after primary ASPS diagnosis. Being male, >20 years of age, having a primary tumour size ≥ 5 cm, and local recurrence were associated with a greater rate of lung metastasis. Median survival after the diagnosis of lung metastasis was 34 months. The 5-year survival rates were 64.1 and 95.2 % for patients with and without lung metastasis (P < 0.001). Thirty-seven patients with metastatic lung disease received anthracycline- and ifosfamide-based chemotherapy. One patient experienced a partial remission. CONCLUSIONS: ASPS patients have a high prevalence of lung metastasis. Sex, age, primary tumour size, and local recurrence are major factors influencing lung metastasis. Chemotherapy is not efficacious in ASPS patients with lung metastasis.
Assuntos
Extremidades/cirurgia , Neoplasias Pulmonares/terapia , Sarcoma Alveolar de Partes Moles/terapia , Neoplasias de Tecidos Moles/terapia , Adolescente , Adulto , Fatores Etários , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Criança , Estudos de Coortes , Extremidades/patologia , Feminino , Humanos , Ifosfamida/administração & dosagem , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Sarcoma Alveolar de Partes Moles/secundário , Fatores Sexuais , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida , Adulto JovemRESUMO
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P < 2.03 × 10(-3) were observed between LN and MYH9 in EAs (N = 4620), with the most pronounced association at rs2157257 (P = 4.7 × 10(-4), odds ratio (OR) = 1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.
