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The aim of the study was to demonstrate the expression of Toll-like receptor (TLR)-8 and to confirm the expression of TLR-7 on bladder transitional cell carcinomas (TCCs) analyzing the changes in expression between low-grade (LG) and high-grade (HG) and between non-muscle invasive (NMIBC) and muscle-invasive (MIBC) bladder cancers. In our study, 25 patients who underwent transurethral resection (TURB) for bladder TCC have been selected. Thirteen of those had an LG form,while the other cases were classified as HG; the lesions were NMIBC in 18 patients and MIBC in the others seven. The analysis of TLRs expression has been performed by immuno histochemistry. TRL-8 expression seems to be higher in MIBC (85%) than in NMIBC (78%), but it is associated with a reduced percentage of immuno reactive cells and with a lower intensity. The expression had a large nuclear localization in NMIBC (80%), althoughit was mainly cytoplasmic in MIBC (72%). TLR-7 was expressed in all NMIBC samples (where the localization was mainly nucleo-cytoplasmic) and in the 71% of MIBC samples (mainly in the nucleus). A higher expression of TRL-8 in HG TCC had been observed, while TRL-7 seems to be more expressed in LG forms. Our study allowed to document the immunohistochemical expression of TLR-8 in TCCs, confirm the immunohistochemical expression of TLR-7, and suggest an increased expression of TLR-7 in LG TCC and NMIBC, and a prevalent expression of TLR-8 in HG TCC and MIBC.

Introduction: Premature ejaculation (PE) is a sexual dysfunction with high prevalence. According to some reports, it is present in about 20-30% of the male population. Since 2009 PE has been treated with a novel inhibitor of serotonin re-uptake, Dapoxetine, which has been reported to be specifically active for PE., Materials and Methods: 59 patients have been selected among the patients affected by PE observed at the outpatient department of Urology and Andrology of the "Paolo Giaccone" University Policlinic Hospital of Palermo. Diagnosis was confirmed unequivocally in all patients, who were suitable for drug treatment and accepted to participate in the study. They were divided in 2 groups: one receiving Dapoxetine (41 patients), another (18 patients) receiving Citalopram. Patients were followed up by telephone at monthly intervals, in order to compare compliance, efficacy and side effects:, Results: Compliance to treatment was obtained in 56% of patients treated with Dapoxetine and in 61% of those treated with Citalopram. In the Dapoxetine group side effects were reported in 14.6% versus 38.4% in the Citalopram group. Benefit from the treatment was reported in 82% and 69.2%, respectively.

Background: Patients with multiple sclerosis (MS) who have a favourable clinical status several years after disease onset are classified as 'benign'. In many cases brain tissue damage does not differ between benign MS and the 'classical' MS forms., Objective: To assess whether the favourable clinical course in benign MS could be explained by the presence of an efficient functional cortical reorganization., Method: Twenty-five right-handed patients with benign MS (defined as having Expanded Disability Status Scale ≤ 3 and disease duration >15 years) underwent functional MRI during a simple motor task (right-hand tapping) to assess movement-associated brain activation. This was compared with that of 10 patients with relapsing-remitting MS and 10 normal controls. Benign MS patients also underwent conventional brain MRI and magnetization transfer imaging, which was compared with an identical examination obtained 1 year before. Quantitative structural magnetic resonance measures were baseline and changes over time in T2-lesion volume, magnetization transfer ratio in T2 lesions and normal-appearing brain and total brain volume., Results: Movement-related activation was greater in patients with benign MS than in those with relapsing-remitting MS or normal controls, extensively involving bilateral regions of the sensorimotor network as well as basal ganglia, insula and cerebellum. Greater activation correlated with lower T2-lesion magnetization transfer ratio, and with decreasing brain volume and increasing T2 lesion volume., Conclusions: The results suggest that bilateral brain networks, beyond those normally engaged in motor tasks, are recruited during a simple hand movement in patients with benign MS. This increased activation is probably the expression of an extensive, compensatory and tissue-damage related functional cortical reorganization. This can explain, at least in part, the favourable clinical expression of patients with benign MS.

Significant cognitive impairment has been found in 20-30% of patients with clinically isolated syndromes suggestive of multiple sclerosis. In this study we aimed to assess the prognostic value of the presence of cognitive impairment for the conversion to multiple sclerosis in patients with clinically isolated syndromes. All patients with clinically isolated syndromes consecutively referred to our centre since 2002 and who had been followed-up for at least one year underwent cognitive assessment through the Rao's Battery and the Stroop test. Possible predictors of conversion to clinically definite multiple sclerosis were evaluated through the Kaplan Meier curves and Cox regression analysis. A total of 56 patients (41 women; age 33.2 +/- 8.5 years; expanded disability scale score 1.2 +/- 0.7) were recruited. At baseline, 32 patients (57%) fulfilled McDonald's criteria for dissemination in space. During the follow-up (3.5 +/- 2.3 years), 26 patients (46%) converted to a diagnosis of multiple sclerosis. In particular, 64% of patients failing >or= 2 tests and 88% of patients failing >or= 3 tests converted to multiple sclerosis. In the Cox regression model, the failure of at least three tests (HR 3.3; 95% CI 1.4-8.1; p = 0.003) and the presence of McDonald's dissemination in space at baseline (HR 3.8; 95% CI 1.5-9.7; p = 0.005), were found to be predictors for conversion to multiple sclerosis. We conclude that cognitive impairment is detectable in a sizable proportion of patients with clinically isolated syndromes. In these subjects cognitive impairment has a prognostic value in predicting conversion to multiple sclerosis and may therefore play a role in therapeutic decision making.

The objective of this article was to assess the association between apolipoprotein E (APOE)-epsilon4 and cognitive impairment (CI) in relapsing-remitting multiple sclerosis (RRMS). The APOE genotype was assessed in 85 RRMS cases (58 females, mean age 43 +/- 8.4 years, mean disease duration 15.8 +/- 9.6 years, mean Expanded Disability Status Scale (EDSS) 1.7 +/- 1.0). Cognitive functioning was evaluated in the whole sample using Rao's Brief Repeatable Battery (BRB). Performance on each test was assessed by applying the normative values for the Italian population. In a subgroup of 50 patients, a brain magnetic resonance (MR) study was performed including measurement of T2 lesion volumes (T2LV), neocortical volume (NCV) and normalized brain volume (NBV). The relationship between APOE genotype, CI and MR variables was assessed through univariate and multivariate logistic regression models. CI, most commonly involving complex attention and verbal memory tasks, was found in 28 cases (33%). We identified a total of 19 epsilon4carriers (22.4%), who did not differ from non-carriers regarding clinical and demographic characteristics. The presence of the epsilon4 genotype was associated with neither CI (p = 0.28) nor impairment on each neuropsychological test (p > 0.32; corrected for age, gender, disease duration, EDSS, depression and fatigue). The APOE genotype and CI were also not related in the subgroup of younger patients (age < 45 years; p > 0.9). Moreover, CI was related to higher T2LV (p = 0.008) and lower NCV (p = 0.006). In conclusion, in our sample CI was associated with higher subcortical damage and cortical atrophy but not with APOE-epsilon4 genotype. The role of APOE-epsilon4 as a possible biomarker in multiple sclerosis is still questionable.

Background: McDonald Criteria (MDC) have been validated in selected patients at high risk for multiple sclerosis (MS). However, possible overdiagnosis of MS can represent critical issues in less controlled clinical settings., Objective: To assess the contribution of oligoclonal bands (OB) to MS diagnosis in current clinical practice., Methods: We included all the patients admitted to our Department since 2001 who had undergone diagnostic workup for a possible MS diagnosis, followed up for at least 1 year. We assessed the accuracy of MDC, OB, and two MDC definitions of dissemination in space (DIS-MRI: fulfillment of MRI criteria, DIS-OB: two MRI lesions+OB)., Results: We included 118 patients (median follow-up 4.0 years). Twenty-eight cases received an alternative diagnosis, whereas none of these presented OB, 43% fulfilled the DIS-MRI criteria. OB were present in 70% of the remaining 90 patients. By the end of the follow-up, 56% of the diagnoses had converted to clinically definite MS and OB showed higher accuracy than DIS-MRI fulfillment (70% vs 58%). Moreover, after 1 year and at the end of the follow-up, DIS-OB yielded a higher Specificity level in comparison with DIS-MRI., Conclusion: OB can improve overall diagnostic Accuracy by increasing Specificity and negative predictive value.

Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a rescue treatment in multiple sclerosis (MS) patients not responding to first- or second-line therapies. To date, most of the treated cases had a secondary progressive disease course. However, patients with high inflammatory activity, but no secondary progression of the disease, could be candidates to take greater advantage of AHSCT. In this paper, we report two cases with very active, relapsing-remitting (RR) MS, who underwent AHSCT, and obtained a dramatic resolution to disease activity.

We assessed the proportion and potential predictors of response to interferon-beta (IFNbeta) therapy in relapsing remitting (RR) multiple sclerosis (MS) patients, comparing different definitions of response: a) lower relapse rate during therapy compared to the year and the two years before therapy, b) reduction of relapse rate during therapy of at least 30% compared to the two years before therapy, c) no relapse during treatment, d) no progression on the Expanded Disability Status Scale (EDSS). Among 147 RR patients treated for at least one year, 33 received IFNbeta-1b subcutaneously (SC) (Betaferon), 59 IFNbeta-1a intramuscularly (Avonex) and 55 IFNbeta-1a SC (Rebif). Using definitions a), b) and d), 72%, 73% and 73% patients, respectively, were considered responders. Forty-four per cent of our patients were completely relapse free. In the logistic regression model, using definitions a) and b), a higher relapse rate in the two years preceding the therapy turned out to be a significant predictor of response. Considering definition c), lower baseline relapse rate was associated with a more favourable response.

To assess the safety and tolerability of cyclophosphamide (CTX) 'pulse' therapy in progressive or very active multiple sclerosis (MS), we reviewed our experience in a cohort of MS patients who have been treated and prospectively followed-up in our Department since 1997. One hundred and twelve patients received intravenous CTX in monthly 'pulses' for 12 months at the dosage of 700 mg/m2 of body surface, then bimonthly for another 12 months. We evaluated the frequency and the severity of side-effects, as well as overall tolerability by the patient perspective using a visual analogue scale (VAS). Side-effects resulted in the discontinuation of therapy in 20 (18%) cases. Serious side-effects were observed in 24 patients (21.4%), most commonly definitive amenorrhea (33.3% of fertile women), hypogammaglobulinemia (5.4%), and hemorrhagic cystitis (4.5%). Malignancies were diagnosed in four (3.6%) subjects, three of whom were previously treated with azathioprine (AZA). Finally, 81.8% of the patients judged the treatment regimen as very or relatively acceptable and tolerable. Our data point to a reasonable safety and tolerability of CTX 'pulse' therapy. Further trials are needed to definitively assess the efficacy of CTX as an alternative therapeutic option for progressive or very active MS.

We assessed the interobserver agreement on the diagnosis of multiple sclerosis (MS) in a study sample consisting of 41 MS (15 relapsing remitting, two secondary progressive, five primary progressive and 19 presenting their first clinical attack) and three non-MS cases. Clinical and paraclinical information was recorded in standardized forms. Four neurologists were asked to make a diagnosis using Poser's and McDonald's criteria and to assess MRI scans according to the McDonald's guidelines. In terms of the kappa statistic (kappa), we found a moderate agreement on the overall diagnosis using both Poser's and McDonald's criteria (kappa, respectively 0.57 and 0.52). As for distinct diagnostic categories, we observed a moderate to substantial agreement for the three McDonald categories (range of kappa values 0.49-0.64) and a fair to substantial agreement for the nine Poser categories (range of kappa values 0.37-0.67). Taking into account clinical information, the agreement on dissemination over time was substantially higher (kappa = 0.69) than that found on dissemination over space (kappa = 0.46). In contrast, for MRI assessment, the agreement for spatial dissemination was substantial (kappa = 0.74) compared with the fair agreement (kappa = 0.25) yielded by dissemination over time. The new McDonald's criteria yield a good overall diagnostic reliability, and compare favourably with Poser's classification in terms of agreement on distinct diagnostic categories.