390 research outputs found

    Intimité et sexualité des patientsPoint de vue du personnel hospitalier

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    Quotidiennement, les soignants entrent dans la sphère intime du patient. De plus, ils ont à se position- ner à propos de questions difficiles, telles que la place à laisser à la sexualité du patient, la réaction à avoir face à des comportements «inadéquats», etc. Comment vivent-ils cette confrontation à l'inti- mité ? Quelles sont leurs ressources en termes de savoir-faire, formation, directives ? Quelles sont les différentes approches de la sexualité et l'intimité parmi les soignants ? Douze soignants ont participé à des entretiens semi-dirigés. Ces entretiens ont été analysés afin de faire ressortir les manières de réagir des soignants face à l'intimité. De plus, des experts ont répondu à des questions concernant le contenu de la formation ou les directives des hôpitaux. Beaucoup de réflexions qui permettent aux soignants de vivre au mieux la confrontation à l'intimité ont été dégagées. Voici deux exemples de réflexions importantes : de quelle manière et dans quel but exposer ou parler de l'intimité du patient ? Comment ajuster la distance thérapeutique en fonction du patient et de la situation ? Quatre manières d'aborder la sexualité ont été identifiées : inexpérimentée et fragile chez le «stagiaire» ; médicale et factuelle chez le «technicien» ; pudique, comme un sujet privé chez le «décent» ; et finalement attentive chez le «compréhensif». Actuellement, il n'existe pas de directives spécifiques au sujet de l'intimité et la sexualité des patients dans nos hôpitaux. En ce qui concerne la formation, le sujet souvent abordé est la protection de la pudeur lors des soins. Le sujet qui fait défaut est la gestion des situations complexes ou liées à la sexualité. Chaque soignant aborde la sexualité de manière très différente. Il est difficile d'élaborer des directives qui correspondent à chaque soignant et à chaque nouvelle situation. C'est pourquoi il faut se concen- trer sur la formation et la sensibilisation des soignants à cette problématique. Ceci leur permet de se préparer à la confrontation à l'intimité en y réfléchissant à l'avance

    Transcriptional silencing of the Dickkopfs-3 (Dkk-3) gene by CpG hypermethylation in acute lymphoblastic leukaemia

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    Dkk-3 is a newly characterised mortalisation-related gene and an antagonist of the Wnt oncogenic signalling pathway whose expression is decreased in a variety of cancer cell lines, suggesting that the Dkk-3 gene, located at chromosome 11p15.1, functions as a tumour suppressor gene. Although 11p15 is a ‘hot spot’ for methylation in acute lymphoblastic leukaemia (ALL), the role of Dkk-3 abnormalities has never been evaluated in this disease. We analysed CpG island methylation of the Dkk-3 promoter in six ALL cell lines and 183 ALL patients. We observed Dkk-3 hypermethylation in all cell lines and in cells from 33% (60/183) of ALL patients. Moreover, Dkk-3 methylation was associated with decreased Dkk-3 mRNA expression and this expression was restored after exposure to the demethylating agent 5-AzaC. Clinical features did not differ between hypermethylated and unmethylated patients. Estimated disease-free survival (DFS) and overall survival at 10 and 11 years, respectively, were 49.8 and 45.6% for normal patients and 10.5 and 15.1% for hypermethylated patients (P¼0.001 and 0.09). Multivariate analysis demonstrated that Dkk-3 methylation was an independent prognostic factor predicting DFS (P¼0.0009). Our data suggest that Dkk-3 methylation occurs at an early stage in ALL pathogenesis and probably influences the clinical behaviour of the disease

    Methylation status of Wnt signaling pathway genes affects the clinical outcome of Philadelphia-positive acute lymphoblastic leukemia

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    The clinical significance of aberrant promoter methylation of the canonical Wnt pathway antagonist genes (sFRP1, sFRP2, sFRP4, sFRP5, Wif1, Dkk3, and Hdpr1) and also putative tumor-suppressor gene Wnt5a, belonging to the non-canonical Wnt signaling pathway, was investigated in a large series of 75 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia by methylationspecific polymerase chain reaction. At least one methylated gene was observed in cells from 66% (49/75) of patients (methylated group). Disease-free survival and overall survival at 9 years were 51 and 40%, respectively, for the unmethylated group and 3 and 2%, respectively, for the methylated group (both P < 0.0001). Multivariate analysis demonstrated that the Wnt methylation profile was an independent prognostic factor predicting disease-free survival (P = 0.007) and overall survival (P = 0.039). Abnormal DNA methylation of promoter-associated CpG islands in the Wnt signaling pathway is very common in Philadelphia chromosome-positive acute lymphoblastic leukemia and potentially defines subgroups with distinct clinical characteristics

    Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia

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    Promoter hypermethylation plays an important role in the inactivation of cancerrelated genes. This abnormality occurs early in leukemogenesis and seems to be associated with poor prognosis in acute lymphoblastic leukemia (ALL). To determine the extent of hypermethylation in ALL, we analyzed the methylation status of the CDH1, p73, p16, p15, p57, NES-1, DKK-3, CDH13, p14, TMS-1, APAF-1, DAPK, PARKIN, LATS-1, and PTEN genes in 251 consecutive ALL patients.Atotal of 77.3% of samples had at least 1 gene methylated, whereas 35.9% of cases had 4 or more genes methylated. Clinical features and complete remission rate did not differ among patients without methylated genes, patients with 1 to 3 methylated genes (methylated group A), or patients with more than 3 methylated genes (methylated group B). Estimated disease-free survival (DFS) and overall survival (OS) at 11 years were 75.5% and 66.1%, respectively, for the nonmethylated group; 37.2% and 45.5% for methylated group A; and 9.4% and 7.8% for methylated group B (P < .0001 and P .0004, respectively). Multivariate analysis demonstrated that the methylation profile was an independent prognostic factor in predicting DFS (P < .0001) and OS (P .003). Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in AL

    Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia

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    Cancer testis antigens (CTA) provide attractive targets for cancer-specific immunotherapy. Although CTA genes are expressed in some normal tissues, such as the testis, this immunologically protected site lacks MHC I expression and as such, does not present self antigens to T cells. To date, CTA genes have been shown to be expressed in a range of solid tumors via demethylation of their promoter CpG islands, but rarely in chronic myeloid leukemia (CML) or other hematologic malignancies
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