Minimally Invasive Transanal Repair of Rectourethral Fistulas

Background

Rectourethral fistulas (RUFs) represent an uncommon complication of pelvic surgery, especially radical prostatectomy. To date there is no standardised treatment for managing RUFs. This represents a challenge for surgeons, mainly because of the potential recurrence risk.

Azathioprine in multiple sclerosis

Azathioprine is an immunosuppressive and steroid-sparing purine analogue, used in the treatment of several autoimmune diseases. In multiple sclerosis, available evidence suggests that oral azathioprine reduces relapse rates, provides a slight benefit on disability, and reduces new inflammatory lesions. Here, we focus on molecular mechanisms of Azathioprine and on its usefulness in multiple sclerosis.     

Functional antagonism between nociceptin/orphanin FQ (N/OFQ) and corticotropin-releasing factor (CRF) in the rat brain: evidence for involvement of the bed nucleus of the stria terminalis

Rationale Nociceptin/orphanin FQ (N/OFQ) has been proposed to be a functional antagonist of corticotropin-releasing factor (CRF) in relation to its anti-stress action and its ability to antagonize the anorectic effect of CRF in rats without exhibiting affinity for CRF receptors. The bed nucleus of the stria terminalis (BST) is highly sensitive to the inhibitory effect of N/OFQ on CRF-induced anorexia. Objective The present study was aimed at further evaluating the role of the BST in the functional antagonism between N/OFQ and CRF by examining it at molecular level and in the context of CRF-induced anxiety in the rat. Materials and methods First, in situ hybridization experiments investigated the expression of the pro-N/OFQ precursor and of NOP receptors in several brain areas 6 h after injection of CRF (0.2 and 1 μg/rat) into the lateral cerebroventricle (LV). Second, the elevated plus maze test was used to evaluate whether N/OFQ, injected into the BST (0.05 and 0.5 μg/rat) or into the LV (0.5, 1.8, and 2.4 μg/rat), inhibits the anxiogenic-like effect evoked by LV injection of CRF (1 μg/rat) in rats. Results The in situ hybridization study showed that LV injection of CRF 1 μg/rat increases NOP receptor expression in the BST, while no change of the N/OFQ precursor was observed. On the other hand, N/OFQ injection into the BST blocks the anxiogenic effect of CRF at doses lower than those required by LV injection (0.5 vs 1.8 μg/rat, respectively). Conclusion These data provide further support for the hypothesis that N/OFQ may behave as functional antagonist of CRF and suggest that this antagonism may occur within the BST.     

Grey Matter Density Predicts the Improvement of Naming Abilities After tDCS Intervention in Agrammatic Variant of Primary Progressive Aphasia

Agrammatic variant primary progressive aphasia is a neurodegenerative disorder specifically characterized by language deficits. A recent study has demonstrated a beneficial effect of transcranial direct current stimulation (tDCS) in combination with language training on naming accuracy in these patients. The aim of the study was to evaluate whether the improvement of naming accuracy after tDCS during language training was related to regional grey matter (GM) density. Eighteen avPPA patients underwent a brain magnetic resonance imaging before receiving a treatment that consisted of tDCS over the left dorsolateral prefrontal cortex during individualized language training (10 daily therapy sessions, 5 days per week from Monday to Friday). Performances on neuropsychological tests and naming of objects (treated and untreated) and actions were assessed at baseline, post-treatment  and 3 months after treatment. Correlations between individual changes after treatment on neuropsychological tests and on picture naming task and voxel-based GM volume at baseline were performed. We found that the improvement in the naming of treated objects was positively correlated with GM volume in the left fusiform, left middle temporal, and right inferior temporal gyri whereas action naming change was related to GM density in the left middle temporal gyrus. In conclusion baseline density of GM in these brain regions was associated with greater treatment response on naming performances, suggesting that intervention in early disease stages might be most successful. These findings have implication for designing future rehabilitation protocols in language variants of frontotemporal dementia.     

High homogeneity of MAGE,BAGE, GAGE,Tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simultaneous metastases of human melanoma: Implications for protocol design of therapeutic antigen-specific vaccination strategies

Human melanoma cells express several antigens which are recognized by autologous and specific CTL clones in association with HLA-class-I molecules. Many of these antigens represent suitable targets for tumor immunotherapy, since their expression in human melanoma cells is common and highly specific. In order to achieve real clinical success with therapeutic vaccination strategies, one important requirement is the expression of the target antigen by all the tumor lesions of a patient. We have studied this issue by assessing, through an RT-PCR approach, the expression of MAGE-1, MAGE-2, MAGE-3, BAGE, GAGE-1/2, Tyrosinase and Melan-A/MART-1 genes in 17 clusters of simultaneous in-transit or regional lymph-node metastases collected from 15 stage-III and 1 stage-IV (AJCC/UICC pTNM system) melanoma patients. In 14 out of 17 clusters of simultaneous metastatic lesions (82%), the homogeneity in the pattern of gene expression within the cluster was complete. Heterogeneity within the same cluster was observed in only 3 out of 17 clusters (18%) and represented only minor features. Our data reveal that, in AJCC-stage-III melanoma patients, different but simultaneous metastatic lesions express the same pattern of antigen-coding genes. These observations have 2 main clinical implications: (i) the antigenic characterization of one single and easily accessible lesion allows identification of optimal targets for an active antigen-specific immunotherapy treatment; (ii) almost all the metastatic lesions are expected to be hit by the immune response eventually induced against the tumor antigen. Moreover, these data suggest that active specific immunotherapy directed against MAGE-1, MAGE-3, BAGE, GAGE-1/2, Melan-A/MART-1 and Tyrosinase antigens could be exploited as an adjuvant treatment to surgery in high-risk AJCC-stage-III-melanoma patients. Int. J. Cancer 77:200–204, 1998.© 1998 Wiley-Liss, Inc.