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1.
Br J Cancer ; 113(9): 1313-22, 2015 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-26528707

RESUMO

BACKGROUND: Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs. METHODS: Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT-PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan-Meier estimates and Cox regression. RESULTS: We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29-0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31-0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44-3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28-0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19-0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29-0.73); P=0.001). CONCLUSIONS: RANK/OPG ratio of expression in primary ccRCC is associated with BM and prognosis in patients treated with anti-VEGFR-TKIs. Prospective validation is warranted.


Assuntos
Neoplasias Ósseas/patologia , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Osteoprotegerina/genética , Proteínas Tirosina Quinases/antagonistas & inibidores , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Neoplasias Ósseas/genética , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Genes src/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Proto-Oncogene Mas , Ligante RANK/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
2.
Vox Sang ; 100(3): 303-11, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21091697

RESUMO

BACKGROUND AND OBJECTIVES: Blood donation can contribute to iron deficiency. The possibly resulting anaemia importantly affects donor return rate. The determination of serum ferritin levels revealed iron deficiency in many non-anaemic premenopausal female blood donors at our Institution. We started an iron substitution programme targeting this donor group to prevent anaemia and enhance donor retain. MATERIALS AND METHODS: Women aged≤50 with haemoglobin levels adequate for donation and serum ferritin≤10 ng/ml were offered iron supplementation. Substitution lasted 16 weeks and the donation interval was extended. History collection including iron deficiency-related symptoms, whole blood count and serum ferritin determination was performed at baseline and after 2 and 6 months. Data were recorded prospectively and compared with those of 108 female controls with iron deficiency not receiving iron substitution (retrospective data). RESULTS: Of the 116 participating subjects, 60% completed the programme. Significant results were serum ferritin increase (from a mean value of 7.12 to 25.2 ng/ml), resolution of prostration, fatigue, sleep disturbances, tension in the neck, hair loss and nail breakage. No case of anaemia occurred. Sixty per cent of the women completed the programme and donated blood again. CONCLUSIONS: Targeted iron substitution prevents the development of anaemia and enhances donation return in premenopausal female blood donors with iron deficiency.


Assuntos
Doadores de Sangue , Deficiências de Ferro , Ferro da Dieta/administração & dosagem , Adulto , Feminino , Ferritinas/sangue , Hemoglobinas/análise , Humanos , Ferro/sangue , Ferro da Dieta/uso terapêutico , Pessoa de Meia-Idade , Projetos Piloto , Pré-Menopausa , Resultado do Tratamento , Adulto Jovem
3.
J Neurol Neurosurg Psychiatry ; 77(4): 513-4, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16543532

RESUMO

BACKGROUND: The number of older people with cognitive impairment being seen in out patient settings is increasing. A brief screening test, which is culturally and educationally fair, would be very useful for clinicians for identifying dementia in these settings. OBJECTIVES: To examine the new cognitive screening test, the Rowland Universal Dementia Assessment Scale (RUDAS), and to compare it with the Mini-Mental State Examination (MMSE). METHOD: We administered MMSE and RUDAS to 116 subjects, consisting of 58 patients with mild to moderate dementia and 58 age and sex matched controls. The two screening tests were compared with regard to sensitivity and specificity. We looked at the correlation of both tests with years of formal education among the controls. RESULT: RUDAS had a similar sensitivity but better specificity than MMSE, but did have an educational bias. CONCLUSIONS: RUDAS is a useful brief screening test in clinical settings.


Assuntos
Demência/diagnóstico , Demência/epidemiologia , Programas de Rastreamento/métodos , Testes Neuropsicológicos , Idoso , Área Programática de Saúde , Feminino , Humanos , Índia/epidemiologia , Masculino , Prevalência , Estudos Prospectivos , Índice de Gravidade de Doença
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