Contrast-enhanced ultrasonography in the diagnosis of upper urinary tract urothelial cell carcinoma: a preliminary study.

PURPOSE: The main objective was to assess the effectiveness of contrast-enhanced ultrasonography (CEUS) in the diagnosis of upper urinary tract malignancies by comparing with multidetector computed tomographic urography (MDCTU) and magnetic resonance urography (MRU). Secondary objectives were to compare the tumor size measured with CEUS, MDCTU and MRU and to assess the usefulness of CEUS in distinguishing high-grade tumors from low-grade ones. MATERIALS AND METHODS: In connection with this prospective study carried out from January 2009 to September 2011, 18 patients underwent MDCTU or MRU, grayscale ultrasonography (US), color Doppler ultrasonography and CEUS followed by surgery and histological examination of the specimen. Quantitative analysis was performed using perfusion software. Time intensity curves were extracted and the following parameters were considered: wash-in time, time-to-peak, maximum signal intensity and wash-out time. RESULTS: Grayscale US identified 15/18 lesions; color Doppler showed no flow signal in 8 lesions, low color signal in 9 lesions and an intense color signal in 1 lesion; CEUS identified 17/18 lesions with the undetected lesion being the smallest one (1.2 cm) located in the upper pelvicalyceal system. Semi-quantitative analysis produced different data for high-grade and low-grade urothelial cell carcinoma (UCC). All detected upper urinary tract masses were UCCs. MRU, MDCTU and grayscale US overestimated the tumor size, while CEUS was the most accurate. CONCLUSION: CEUS is useful for evaluating upper urinary tract masses as this method permits differentiation between high-grade and low-grade tumors as well as distinction of the tumor from the adjacent structures and accurate mass measurements.

A prospective randomized study to compare pelvic floor rehabilitation and dapoxetine for treatment of lifelong premature ejaculation.

Premature ejaculation (PE) is the most common male sexual disorder. We compared pelvic floor muscle rehabilitation to on-demand treatment with the selective serotonin reuptake inhibitor dapoxetine in 40 men with lifelong PE (baseline intra-vaginal ejaculatory latency time (IELT) ≤1 min). Subjects were randomized into the following two treatment groups: (1) PFM rehabilitation or (2) 30 or 60 mg of on-demand dapoxetine. Total treatment time for both groups was 12 weeks, at the end of which, IELT mean values were calculated to compare the effectiveness of the two different therapeutic approaches. At the end of treatment, 11 of the 19 patients (57%) treated with rehabilitation were able to control the ejaculation reflex, with a mean IELT of 126.6 sec (range: 123.6-152.4 sec). In the dapoxetine group, after 12 weeks of therapy, 5 of 8 (62.5%) patients in the 30 mg subgroup and five of seven (72%) in the 60 mg subgroup had an IELT >180 sec (mean: 178.2 and 202.8 sec, respectively). The results obtained in the group treated with pelvic floor rehabilitation are promising, and this treatment represents an important cost reduction if compared to dapoxetine on-demand treatment. The present study confirms the data that are previously available in the literature on the efficacy and safety of the new inhibitor of serotonin reuptake, dapoxetine, as well as proposes and evaluates a new type of physical treatment that may be a viable therapeutic option for treatment of PE.

Role of low-mechanical index CEUS in the differentiation between low and high grade bladder carcinoma: a pilot study.

PURPOSE: To assess the efficacy of low-mechanical index contrast-enhanced ultrasonography (CEUS) in the differentiation of a series of histologically proven bladder lesions identified via conventional cystoscopy and biopsied. MATERIALS AND METHODS: 36 patients (mean age: 62 years; range 45 - 72 years) with bladder lesions previously detected by color power Doppler ultrasonography (CDUS) were prospectively examined with low-mechanical index contrast-enhanced US after bolus administration of 2.4 ml of Sonovue (Bracco, Milan, Italy). All lesions were evaluated in real-time continuous scanning for 2 minutes and the videos were registered. Two ultrasound (US) experts evaluated the videos by consensus and assigned a score to the enhancement pattern. Subsequently, a specific sonographic quantification software (Qontrast, Bracco, Milan, Italy) based on pixel by pixel signal intensity over time was used to obtain contrast-enhanced sonographic perfusion maps for each lesion. Time-intensity curves (TICs) of each lesion were then extracted from the region of interest positioned within the lesion and in the closest bladder wall. The sensitivity and specificity of CDUS and CEUS were compared using McNemar's test. All patients subsequently underwent conventional cystoscopy with biopsy or transurethral resection. RESULTS: 22 high-grade and 14 low-grade transitional cell carcinomas (TCCs) were histologically diagnosed (mean diameter 2.1 cm; range: 1 - 4.5 cm). The sensitivity and specificity of CDUS were 86.4% (19 / 22; 95% CI = 66.7 - 95.3%) and 42.9% (6 / 14; 95% CI = 21.4 - 67.4%), respectively. The sensitivity and specificity of CEUS were 90.9% (20 / 22; 95% CI = 72.2 - 97.5%) and 85.7% (12 / 14; 95% CI = 60.1 - 95.9%), respectively. The sensitivity and specificity of CEUS using TICs were 95.4% (21 / 22; 95% CI = 78.2 - 99.2%) and 85.7% (12 / 14; 95% CI = 60.1 - 95.9%), respectively. There was no significant difference between the sensitivity of CDUS versus CEUS, CDUS versus TIC, and CEUS versus TIC (p > 0.05; McNemar's test). The specificity of CEUS and TIC was significantly higher than that of CDUS (p < 0.05; McNemar test). CONCLUSION: CEUS is a reliable noninvasive method for differentiating low- and high-grade bladder carcinomas since it provides typical enhancement patterns as well as specific contrast-sonographic perfusion curves. However, further studies involving larger patient populations is mandatory to confirm these promising results.

GolP: an atomistic force-field to describe the interaction of proteins with Au(111) surfaces in water.

A classical atomistic force field to describe the interaction of proteins with gold (111) surfaces in explicit water has been devised. The force field is specifically designed to be easily usable in most common bio-oriented molecular dynamics codes, such as GROMACS and NAMD. Its parametrization is based on quantum mechanical (density functional theory [DFT] and second order Möller-Plesset perturbation theory [MP2]) calculations and experimental data on the adsorption of small molecules on gold. In particular, a systematic DFT survey of the interaction between Au(111) and the natural amino acid side chains has been performed to single out chemisorption effects. Van der Waals parameters have been instead fitted to experimental desorption energy data of linear alkanes and were also studied via MP2 calculations. Finally, gold polarization (image charge effects) is taken into account by a recently proposed procedure (Iori, F.; Corni, S. J Comp Chem 2008, 29, 1656). Preliminary validation results of GolP on an independent test set of small molecules show the good performances of the force field.

Including image charge effects in the molecular dynamics simulations of molecules on metal surfaces.

Combinatorial bio-techniques have demonstrated that proteins can be good and even selective binders for several inorganic surfaces, including metals. However, the understanding of the basic physical mechanisms that govern such interactions did not keep up with the success in these experiments. The comprehension of such mechanisms would greatly benefit from the computational investigation of the problem. Because of the complexity of the system, classical molecular dynamics simulations based on an atomistic description appear to be the best compromise between reliability and feasibility. For proteins interacting with metal surfaces, however, methodological improvements with respect to standard Molecular Dynamics (MD) of proteins are needed, since the polarization of the metal induced by the protein (and the surrounding water) is not generally negligible. In this article, we present a simple approach to introduce metal polarization effects (often termed image effects) in MD simulations by exploiting standard features of bio-oriented MD codes such as the widely used GROMACS and NAMD. Tests to show the reliability of the proposed methods are presented, and the results for a model application showing the importance of image effects are also discussed.

The Effect of Arterial Curvature on Blood Flow in Arterio-Venous Fistulae: Realistic Geometries and Pulsatile Flow.

Arterio-Venous Fistulae (AVF) are regarded as the "gold standard" method of vascular access for patients with End-Stage Renal Disease (ESRD) who require haemodialysis. However, up to 60% of AVF do not mature, and hence fail, as a result of Intimal Hyperplasia (IH). Unphysiological flow and oxygen transport patterns, associated with the unnatural and often complex geometries of AVF, are believed to be implicated in the development of IH. Previous studies have investigated the effect of arterial curvature on blood flow in AVF using idealized planar AVF configurations and non-pulsatile inflow conditions. The present study takes an important step forwards by extending this work to more realistic non-planar brachiocephalic AVF configurations with pulsatile inflow conditions. Results show that forming an AVF by connecting a vein onto the outer curvature of an arterial bend does not, necessarily, suppress unsteady flow in the artery. This finding is converse to results from a previous more idealized study. However, results also show that forming an AVF by connecting a vein onto the inner curvature of an arterial bend can suppress exposure to regions of low wall shear stress and hypoxia in the artery. This finding is in agreement with results from a previous more idealized study. Finally, results show that forming an AVF by connecting a vein onto the inner curvature of an arterial bend can significantly reduce exposure to high WSS in the vein. The results are important, as they demonstrate that in realistic scenarios arterial curvature can be leveraged to reduce exposure to excessively low/high levels of WSS and regions of hypoxia in AVF. This may in turn reduce rates of IH and hence AVF failure.

The effect of in-plane arterial curvature on blood flow and oxygen transport in arterio-venous fistulae.

Arterio-Venous Fistulae (AVF) are the preferred method of vascular access for patients with end stage renal disease who need hemodialysis. In this study, simulations of blood flow and oxygen transport were undertaken in various idealized AVF configurations. The objective of the study was to understand how arterial curvature affects blood flow and oxygen transport patterns within AVF, with a focus on how curvature alters metrics known to correlate with vascular pathology such as Intimal Hyperplasia (IH). If one subscribes to the hypothesis that unsteady flow causes IH within AVF, then the results suggest that in order to avoid IH, AVF should be formed via a vein graft onto the outer-curvature of a curved artery. However, if one subscribes to the hypothesis that low wall shear stress and/or low lumen-to-wall oxygen flux (leading to wall hypoxia) cause IH within AVF, then the results suggest that in order to avoid IH, AVF should be formed via a vein graft onto a straight artery, or the inner-curvature of a curved artery. We note that the recommendations are incompatible-highlighting the importance of ascertaining the exact mechanisms underlying development of IH in AVF. Nonetheless, the results clearly illustrate the important role played by arterial curvature in determining AVF hemodynamics, which to our knowledge has been overlooked in all previous studies.

Infections caused by multiple strains of methicillin-resistant Staphylococcus aureus--a pressing epidemiological issue.

The genotype of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from several foci in the same patient was studied to identify the rate of infections caused by multiple MRSA strains during hospitalization. Twenty-one patients with MRSA bacteraemia and other specimens diagnosed between 1990-1994 were studied. Clinical data were retrospectively collected from the medical records. Genotyping of 113 MRSA isolates was performed by pulsed-field gel electrophoresis (PFGE), using the Gene Navigator System. More than one type of MRSA was detected from different foci in eight of 21 (38%) patients, and three types were identified in a single patient. Our results indicate that epidemiological investigations must be conducted carefully, especially in immunocompromised hosts with MRSA bacteraemia, as the probability of infection with multiple strains among these patients is relatively high.

DNA aberrations in urinary bladder cancer detected by flow cytometry and FISH: prognostic implications.

We evaluated the genetic changes in bladder cancer biopsy by fluorescence in situ hybridization (FISH) and related them to stage and grade of the tumor, ploidy (FCM) and clinical outcome, to determine a simple method to identify tumors with a poorer prognosis. Using FISH the numerical aberrations of chromosomes 1, 7, 9, 17 in tumor's imprints of 70 patients with transitional cell cancer (TCC) were determined. First of all, the data demonstrated that the sensitivity of FISH in detecting quantitative DNA aberrations exceeds FCM's sensitivity. The frequency of chromosome 1 and 9 aberrations did not show significant differences in diploid and aneuploid tumors in different stage and grade. On the contrary, the chromosome 7 and 17 aneusomy showed greater differences between pT1 and pT2-3 tumors (p<0.032 and p<0.0006, respectively) than between stage pTa and pT1. In our investigation, an increasing number of aberrations was observed in all chromosomes examined in tumors of patients who afterwards underwent cystectomy and/or had recurrent tumors. These results suggest that chromosome 7 and 17 aneusomy could be predictive of adverse outcome in a subgroup of patients with superficial tumors at presentation.

[Specular crossed renal ectopia and balanic hypospadias in monozygotic twins]. / Ectopia renale crociata speculare ed ipospadia balanica in gemelli monoovulari.

The observation of a balanic hypospadia with chordee associated with a renal malformation in both of identical twins is reported. Monozygosity of twins was demonstrated with the study of ABO, MNS, HLA and RH factor systems. Urography, performed in both twins, showed a specular crossed renal ectopia with fusion. Abdominal ultrasounds, Chest-X-ray and barium meal showed no other abnormalities. After an analysis of the embryogenetic mechanisms of twinning, the Authors elaborate a hypothesis to explain the development of this specular renal malformation, never reported up to date in identical twins.

[Role of urinary cytology in the study of bladder cancer. Comparison with the BTA test]. / Ruolo della citologia urinaria nello studio delle neoplasie vescicali. Confronto con il BTA test.

Early diagnosis of bladder neoplasia at the moment makes use of urinary cytology and cystoscopy. The authors describe the results of a study on 62 patients (56 men and 6 women) with bladder neoplasia, and compare the results of urinary cytology to the BTA test (Bladder Tumor Antigen test), ones, after considering histological results of TURB (Trans Urethral Resection Bladder) or cystectomy. Sensibility of urinary cytology was quite better than BTA test sensibility (80.6% vs 48%). Finally it's described a study on 450 cases of istologically controlled bladder carcinomas, on which had been executed a cytological analysis before surgical treatment. The outcome of cytological diagnosis on 414 cases (92%) was neoplasia. On the basis of their experience, the authors regard cytology as a fundamental method in diagnostic iter and in follow-up of patients with bladder neoplasia.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1994). III. Secular changes in susceptibility].

Susceptibilities of Enterococcus faecalis, Staphylococcus aureus, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Pseudomonas aeruginosa and Serratia spp. isolated from patients with urinary tract infections (UTIs) in 10 hospitals during June 1994 to May 1995 to various antimicrobial agents were compared with those in the same period of previous years according to a classification, uncomplicated UTIs, complicated UTIs without indwelling catheter, and complicated UTIs with indwelling catheter. No remarkable changes were found in susceptibilities of Citrobacter spp., Enterobacter spp. and Serratia spp. The susceptibilities of E. faecalis to amikacin and quinolones were better than those in 1993. As for S. aureus, susceptible strains to all drugs increased in uncomplicated UTIs. Against E. coli in 1993, the antimicrobial activities of piperacillin, cefotiam and aminoglycosides have decreased, however, in 1994, these activities have turned to the better state. As for Klebsiella spp. susceptible strains to ABPC decreased. The susceptibilities of P. mirabilis to all drugs except minocycline were good. Against P. aeruginosa in 1993, the activities of aminoglycosides have decreased, but, in 1994, these activities have turned to the better state. These data should be considered in clinical treatment of various urinary tract infections.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1994). I. Susceptibility distribution].

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 567 bacterial strains isolated from patients with urinary tract infections in 10 hospitals during the period of June 1994 to May 1995. Of the above total bacterial isolates, Gram-positive bacteria accounted for 26.8% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 73.2% and most of them were Escherichia coli. 1. Enterococcus faecalis. Ampicillin (ABPC) and imipenem (IPM) showed the highest activities against E. faecalis isolated from patients with urinary tract infections. The MIC90s of them were 1 microgram/ml. Vancomycin (VCM) was also active with the MIC90 of 2 micrograms/ml. Piperacillin (PIPC) and biapenem (BIPM) were also active with the MIC90s of 4 micrograms/ml and 8 micrograms/ml, respectively. The others were not so active with the MIC90s of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA. VCM showed the highest activities against S. aureus isolated from patients with urinary tract infections. Its MIC90 was 1 microgram/ml against both S. aureus and MRSA. Arbekacin (ABK) was also active with the MIC90 of 2 micrograms/ml. The others except minocycline (MINO) were not so active with the MIC90s of 64 micrograms/ml or above. 3. Staphylococcus epidermidis. MINO showed the strongest activity against S. epidermidis isolated from patients with urinary tract infections. Its MIC90 was 0.25 microgram/ml. ABK was also active with the MIC90 of 1 microgram/ml. Cephems were active with the MIC90s of 2 approximately 16 micrograms/ml, but penicillins and quinolones were not so active with the MIC90s and 64 approximately 128 micrograms/ml. 4. Citrobacter freundii. Gentamicin (GM) showed the highest activities against C. freundii isolated from patients with urinary tract infections. Its MIC90 was 1 microgram/ml. IPM was also active with the MIC90 of 2 micrograms/ml. Cefpirome (CPR) and cefozopran (CZOP) were also active with the MIC90s of 4 micrograms/ml and 8 micrograms/ml. The others were not so active with the MIC90s of 32 micrograms/ml or above. 5. Enterobacter cloacae. IPM showed the highest activities against E. cloacae. Its MIC90 was 0.5 microgram/ml. GM and amikacin (AMK), ciprofloxacin (CPFX) and tosulfloxacin (TFLX) were also active with the MIC90s of 4 micrograms/ml. Penicillins and cephems except latamoxef (LMOX), cefmenoxime (CMX), CPR and CZOP showed lower activities with the MIC90s of 256 micrograms/ml or above. 6. Escherichia coli. Most of antimicrobial agents were active against E. coli. CPR, CZOP, IPM, carumonam (CRMN), CPFX and TFLX showed the highest activities against E. coli. The MIC90s of them were 0.125 microgram/ml or below. Cefotiam (CTM), flomoxef (FMOX) CMX, ceftazidime (CAZ), and LMOX were also active with the MIC90s of 0.25 microgram/ml. Penicillins were not so active with the MIC90s of 128 micrograms/ml or above. 7. Klebsiella pneumoniae. CRMN showed the highest activities against K. pneumoniae. Its MIC90 was < or = 0.125 microgram/ml. CZOP was also active with the MIC90 of 0.25 microgram/ml. Penicillins were not so active with the MIC90s of 128 micrograms/ml or above. 8. Proteus mirabilis. P. mirabilis was susceptible to a majority of drugs. CMX, CAZ, LMOX, CRP, cefpodoxime (CPDX), CRMN, CPFX and TFLX showed the highest activities against P. mirabilis isolated from patients with urinary tract infections. The MIC90s of them were 0.125 microgram/ml or below. MINO was not so active with the MIC90 of 128 micrograms/ml. 9. Pseudomonas aeruginosa. Most of the agents were not so active against P. aeruginosa. IPM showed MIC90 of 8 micrograms/ml. The others were not so active with the MIC90s of 16 micrograms/ml or above. CPFX showed MIC50 of 0.5 microgram/ml.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1994). II. Background of patients].

Clinical background was investigated on 628 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during period from June, 1994 to May, 1995. 1. Distributions of sex, age and urinary tract infections Among over sixties males, the majority was taken by complicated urinary tract infections. Among females, the uncomplicated urinary tract infections was most frequent without a relation of age. As for over 40 females, the increase of complicated UTI was admitted. 2. Distribution of sex, age and pathogens isolated from UTIs In uncomplicated UTIs, Escherichia coli was most frequently isolated without a relation of age, and next Enterococcus faecalis and CNS. In complicated UTIs without indwelling catheter, E. coli, Pseudomonas aeruginosa and E. faecalis were isolated the most frequent. In complicated UTIs with indwelling catheter, P. aeruginosa was most frequently isolated, and next E. faecalis and Staphylococcus aureus. 3. Administration of antimicrobial agents and pathogens isolated from UTIs In uncomplicated UTIs, pathogens, after administration of antibiotics, isolated from patients have obviously decreased from 216 to 32 isolates. And also, pathogens of complicated UTIs without indwelling catheter, have decreased from 127 to 50 isolates. However, in complicated UTIs with indwelling catheter, pathogens after or before administration of antibiotics, were not revealed an obvious change. 4. Pathogens and UTIs with or without factor and operation In uncomplicated UTIs with or without factor and operation, E. coli was mainly detected. In complicated UTIs without indwelling catheter and with factor and operation E. faecalis was mainly detected, and next E. coli, S. aureus and P. aeruginosa. Without factor and operation, E. coli was mainly detected. In complicated UTIs with indwelling catheter and with factor and operation, P. aeruginosa, E. faecalis and S. aureus were mainly detected at 23.5%, 15.0%, 15.0%, respectively. Without factor and operation, Proteus spp. 22%, and next E. faecalis and P. aeruginosa 10% and 12%, were detected, respectively. The distribution of pathogens, in the case of Proteus spp. and P. aeruginosa has been obviously varied by the influence of factor and operation.

CEUS in the differentiation between low and high-grade bladder carcinoma.

INTRODUCTION: Bladder cancer ranks 4th overall in the number of newly diagnosed cancers and 10th in causes of cancer deaths. More than 90% of all cases of bladder cancer are transitional cell carcinoma (TCC). The goal of this study is to confirm the usefulness of low mechanical index contrast-enhanced ultrasonography (CEUS), also in association with time-intensity curves, in the differentiation between high- and low-grade bladder malignant lesions. MATERIALS AND METHODS: From February 2006 to February 2012 we recruited 144 patients. All patients underwent grayscale ultrasonography (US), color-Doppler ultrasonography (CDUS) and contrast-enhanced ultrasonography (CEUS). Subsequently all patients underwent cystoscopy and TURB. RESULTS: HISTOLOGICAL DIAGNOSES WERE: 88 high-grade carcinomas (61.1%), and 56 low-grade carcinomas (38.9%). Sensitivity and specificity of CDUS were 87.5% (126/144) and 60%, respectively. Sensitivity and specificity of CEUS were 90.9% and 85.7%, respectively. Sensitivity and specificity of TIC were 91.6% (132/144) and 85.7%, respectively. DISCUSSION AND CONCLUSIONS: CEUS is a reliable noninvasive method for differentiating low- and high-grade bladder carcinomas since it provides typical enhancement patterns as well as specific contrast-sonographic perfusion curves.