RESUMO
As monozygotic (MZ) twins are believed to be genetically identical, discordance for disease phenotype between MZ twins has been used in genetic research to understand the contribution of genetic vs environmental factors in disease development. However, recent studies show that MZ twins can differ both genetically and epigenetically. Screening MZ twins for genetic and/or epigenetic differences could be a useful and novel approach to identify modifying factors influencing phenotypic expression of disease. MZ twins that are phenotypically discordant for monogenic diseases are of special interest. Such occurrences have been described for Huntington's disease, spinocerebellar ataxias, as well as for familial forms of Alzheimer's disease. By comparing MZ twins that are phenotypically discordant, crucial factors influencing the phenotypic expression of the disease could be identified, which may be of relevance for understanding disease pathogenesis and variability in disease phenotype. Overall, understanding the crucial factors in development of a neurodegenerative disorder will have relevance for predictive testing, preventive treatment and could help to identify novel therapeutic targets.
Assuntos
Doenças Neurodegenerativas/genética , Fenótipo , Gêmeos Monozigóticos/genética , Doença de Alzheimer/genética , Metilação de DNA , Epigênese Genética , Humanos , Doença de Huntington/genética , Ataxias Espinocerebelares/genéticaRESUMO
In this analysis of the safety and efficacy of BAY 43-9006 (sorafenib) -- a novel, oral multi-kinase inhibitor with effects on tumour and its vasculature -- pooled data were obtained from four phase I dose-escalation trials. Time to progression (TTP) was compared in patients with/without grade 2 skin toxicity/diarrhoea. Grade 3 hand-foot skin reactions (HFS; 8%) and diarrhoea (6%) were common. At the recommended 400mg bid dose for phase II/III trials (RDP), 15% of patients experienced grade 2/3 HFS, and 24% experienced grade 2/3 diarrhoea. Sorafenib induced stable disease for 6 months in 12% of patients (6% stabilized for 1 year). Patients receiving sorafenib doses at or close to the RDP, who experienced skin toxicity/diarrhoea, had a significantly increased TTP compared with patients without such toxicity (P < 0.05). Sorafenib was well tolerated at the RDP, and induced sustained disease stabilization, particularly in patients with skin toxicity/diarrhoea.
Assuntos
Antineoplásicos/efeitos adversos , Benzenossulfonatos/efeitos adversos , Toxidermias/etiologia , Exantema/induzido quimicamente , Neoplasias/tratamento farmacológico , Piridinas/efeitos adversos , Administração Oral , Adolescente , Adulto , Idoso , Benzenossulfonatos/administração & dosagem , Ensaios Clínicos Fase I como Assunto , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/administração & dosagem , Sorafenibe , Resultado do TratamentoRESUMO
In this study, the functional and aesthetic outcome of patients with nasolabial flaps in the floor of the mouth was examined. Sixteen patients underwent reconstruction of the floor of the mouth with 19 nasolabial flaps after resection of a squamous cell carcinoma. Eight patients received postoperative radiotherapy. The patients were questioned concerning oral disabilities. Speech, mastication, deglutition, oral continence and the aesthetic result were evaluated. Two-point discrimination, temperature sensation and blunt-sharp discrimination of the intraoral flaps were tested. Speech and the wearing of dentures were hardly affected. Consumption of solid foods caused moderate problems in half of the patients. No sensibility problems were found. The aesthetic deformity was minimal. The use of nasolabial flaps in patients with limited defects of the anterior floor of the mouth after tumor resection showed adequate functional and aesthetic results.
