Pelvic floor muscle tenderness in asymptomatic, nulliparous women: topographical distribution and reliability of a visual analogue scale.

INTRODUCTION AND HYPOTHESIS: Aim of this study is to investigate pelvic floor muscle pain scores in a group of healthy, asymptomatic, nulliparous women using a simple visual analogue scale, and to examine the inter-rater and test-retest reliability of the digital palpation of the pelvic floor muscle. METHODS: Seventeen female volunteers were recruited. Different sites of their pelvic floor muscle were examined digitally according to the suggestions of the International Continence Society from two investigators blinded to the clinical data in two consecutive visits and pain scores were obtained. Level of agreement between investigators, inter-rater and intra-rater reliability were assessed. RESULTS: Overall pain scores were low. There were statistically significant differences between scores at different pelvic sites, with the levator ani showing the lowest scores. Reliability was heterogeneous among pelvic sites, varying from poor to excellent. CONCLUSIONS: Pain upon palpation of the pelvic floor muscle in asymptomatic, nulliparous women should be considered an uncommon finding.

Oncogenic RAS enables DNA damage- and p53-dependent differentiation of acute myeloid leukemia cells in response to chemotherapy.

Acute myeloid leukemia (AML) is a clonal disease originating from myeloid progenitor cells with a heterogeneous genetic background. High-dose cytarabine is used as the standard consolidation chemotherapy. Oncogenic RAS mutations are frequently observed in AML, and are associated with beneficial response to cytarabine. Why AML-patients with oncogenic RAS benefit most from high-dose cytarabine post-remission therapy is not well understood. Here we used bone marrow cells expressing a conditional MLL-ENL-ER oncogene to investigate the interaction of oncogenic RAS and chemotherapeutic agents. We show that oncogenic RAS synergizes with cytotoxic agents such as cytarabine in activation of DNA damage checkpoints, resulting in a p53-dependent genetic program that reduces clonogenicity and increases myeloid differentiation. Our data can explain the beneficial effects observed for AML patients with oncogenic RAS treated with higher dosages of cytarabine and suggest that induction of p53-dependent differentiation, e.g. by interfering with Mdm2-mediated degradation, may be a rational approach to increase cure rate in response to chemotherapy. The data also support the notion that the therapeutic success of cytotoxic drugs may depend on their ability to promote the differentiation of tumor-initiating cells.

Expression profiling reveals specific gene expression signatures in gastric MALT lymphomas.

The purpose of this study is to identify genes that are involved in the etiology of Helicobacter pylori induced gastric MALT lymphoma. We compared gene expression profiles of gastric MALT lymphoma with their corresponding gastric MALT (chronic gastritis with formation of follicles and aggregates). cDNA microarrays were used to compare these two tissue types from the same patient (n = 21). Quantitative PCR and immunohistochemical staining were performed to validate the microarray results. Three hundred and fifty eight out of 11,552 genes were differentially expressed between gastric MALT lymphomas and gastric MALT. Thirty eight genes are implicated in immune response, 66 in signal transduction and 36 in cell proliferation. Interestingly, chromosome 6 was the only chromosome which was significantly over-represented with 25 genes (EASE score p = 0.01254). Several surface markers of haematopoietic cells, such as CD1c, CD40, CD44, CD53, CD83, CD86 and members of the HLA-D family were up-regulated in lymphoma tissues, indicating antigen-dependent survival of lymphoma cells. We conclude that gastric MALT lymphoma shows a specific gene expression profile, which allows the differentiation from H. pylori induced lymphoid gastritis.