Standard Semen Parameters vs. Sperm Kinematics to Predict Sperm DNA Damage.

PURPOSE: The aims of this study were to associate sperm kinematics and standard semen parameters with sperm DNA damage and to evaluate whether the addition of sperm kinematics improve the multivariable prediction of sperm DNA fragmentation compared to standard semen parameters alone. MATERIALS AND METHODS: We evaluated sperm kinematics, standard semen parameters, and DNA fragmentation index (DFI) in 122 men. Univariate and multivariate logistic regression models were fitted to evaluate the association of sperm kinematics and standard semen parameters with pathologically damaged sperm DNA (DFI≥26%), and receiver operating characteristics (ROC) curves were calculated for these models. RESULTS: On univariate analyses, average velocity, curvilinear velocity, straight-line velocity, straightness (STR), beat-cross frequency (BCF), and the percentage of progressive motile sperm cells (PPMS) were significantly associated with pathologically damaged sperm DNA. Likewise, among standard semen parameters, sperm concentration, progressive motility, normal morphology, and vitality were found to be linked with sperm DNA damage. On the multivariate analysis, vitality was the strongest predictor of pathologically damaged sperm DNA with an area under the ROC curve (AUROC) of 88.3%. Adding STR, BCF, and PPMS to vitality increased the AUROC to the significant extent of 91.5%. CONCLUSIONS: Sperm vitality is the most accurate routine-based laboratory test for the prediction of pathologically damaged sperm DNA, but the addition of sperm kinematics increases its accuracy. Both standard semen parameters and sperm kinematics are complementary in predicting pathologically damaged sperm DNA, and might serve as a new tool to screen for fertile men.

The 1999 and 2010 WHO reference values for human semen analysis to predict sperm DNA damage: A comparative study.

Standard semen parameters are often used to predict male fertility, but whether the 2010 World Health Organization (WHO 2010) thresholds are better predictors than the 1999 thresholds has not been investigated. In this study, we addressed this issue using sperm DNA fragmentation (SDF) as a marker of male fertility in 134 subfertile male individuals. To compare the predictive value of the 1999 thresholds with the 2010 cutoffs, the Youden indices (YIs) of all possible thresholds were calculated using receiver operating characteristic (ROC) curves and compared to each other and to the respective YIs of optimal thresholds. We found that the area under the ROC curves of progressive motility and vitality was the highest among standard semen parameters, and that the YI of both parameters from the 2010 manual was comparable to the respective optimal YIs. In contrast, the threshold of sperm concentration and total sperm number from both WHO recommendations demonstrated low YIs, with substantial differences to the respective optimal YIs. The YIs of normal morphology cutoffs from both WHO manuals were slightly different from each other and from the respective optimal YIs. In conclusion, the 2010 thresholds for progressive motility and vitality are superior to the 1999 thresholds in predicting SDF, whereas the cutoff value of sperm concentration, total sperm number and normal morphology may need further revisions to increase their accuracy.

The association of seminal leucocytes, interleukin-6 and interleukin-8 with sperm DNA fragmentation: A prospective study.

The effect of seminal leucocytes on sperm DNA integrity has been discussed controversially in literatures. Moreover, the studies investigating the in vivo effect of pro-inflammatory cytokines interleukin-6 and interleukin-8 on sperm DNA fragmentation are scarce and inconsistent. The association of standard sperm parameters with sperm DNA fragmentation is also a matter of ongoing discussion. Hence, the aims of this study were, first, to evaluate the effect of seminal leucocytes, interleukin-6 and interleukin-8 on sperm DNA integrity and, second, to examine whether standard semen parameters are associated with sperm DNA fragmentation. Seminal leucocytes, interleukin-6, interleukin-8 and standard semen parameters, including total sperm number, sperm concentration, progressive motility, nonprogressive motility, immotility and normal morphology, were determined in 134 consecutive men. The concentrations of seminal leucocytes, interleukin-6 and interleukin-8, did not correlate with sperm DNA fragmentation. In contrast, total sperm number, sperm concentration, progressive motility, nonprogressive motility and normal morphology exhibited significant inverse correlations with sperm DNA fragmentation. Immotile spermatozoa were directly correlated with sperm DNA fragmentation. In conclusion, seminal leucocytes, interleukin-6 and interleukin-8, are not associated with sperm DNA fragmentation. Poor standard semen parameters are significantly related to the high levels of sperm DNA fragmentation.

Evaluation of Leukocyte Threshold Values in Semen to Detect Inflammation Involving Seminal Interleukin-6 and Interleukin-8.

OBJECTIVE: To evaluate leukocyte threshold values in semen to detect inflammation involving seminal interleukin (IL)-6 and IL-8. MATERIALS AND METHODS: The levels of leukocytes, IL-6, and IL-8 in semen were determined. The 75th and 90th percentiles of seminal IL-6 and IL-8 were considered as "high" and "very high" concentrations, respectively. Inflammatory semen was defined based on high levels of IL-6 (≥86.75 pg/mL) or IL-8 (≥4460 pg/mL). Very high levels of IL-6 (≥228 pg/mL) or IL-8 (≥12,480 pg/mL) were used to define acute seminal inflammation. On the basis of high and very high levels of IL-6 or IL-8, receiver operating characteristic curves were generated to evaluate leukocyte threshold values. RESULTS: Leukocytes at a cutoff level of 1 × 10(6)/mL had 51% sensitivity and 95% specificity to detect high levels of IL-6, whereas on the basis of very high levels of IL-6, the same cutoff level revealed 82% sensitivity and 90% specificity. Similarly, leukocytospermia demonstrated low sensitivity (56%) to detect high levels of IL-8 but acceptable sensitivity (94%) and specificity (92%) to predict very high levels of IL-8. The cutoff level of 0.315 × 10(6) leukocytes/mL had optimal sensitivity and specificity for predicting high levels of inflammatory cytokines. CONCLUSION: Leukocytospermia demonstrated poor sensitivity to detect seminal inflammation, as defined by high levels of inflammatory cytokines. The optimal threshold value to detect inflammation was found to be 0.315 × 10(6) leukocytes/mL. On the basis of very high levels of IL-6 or IL-8, leukocytospermia is a sensitive and specific marker to predict acute seminal inflammation.

Utility of cardiac magnetic resonance imaging, echocardiography and electrocardiography for the prediction of clinical response and long-term survival following cardiac resynchronisation therapy.

Cardiac resynchronisation therapy (CRT) can reduce symptoms, hospitalisations, and mortality in patients with severe left ventricular (LV) systolic dysfunction and electro-mechanical dyssynchrony. Unfortunately, approximately 30 % of eligible patients fail to respond to CRT. This study prospectively compared electrocardiography (ECG), echocardiography, and cardiac magnetic resonance (CMR) imaging for the prediction of response to CRT. We performed ECG, echocardiography and CMR on 46 patients prior to planned CRT implantation. Patients were divided into predicted responder and non-responder groups using previously described criteria for each modality. Changes in indicators of CRT response were recorded 6 months post-implantation, and later for transplant-free survival. Less dyspnoea, lower levels of N-terminal pro-brain natriuretic peptide, more LV reverse remodelling, and longer transplant-free survival were observed in predicted responders compared to predicted non-responders using each of the three modalities (p < 0.05 for each comparison). Additionally, for patients with QRS duration <150 ms and/or non-left bundle branch block (non-LBBB) QRS morphology, CMR predicted both clinical response and improved longer term transplant-free survival (80 % transplant-free survival in predicted responders vs. 20 % in predicted non-responders, p = 0.04). ECG and cardiac imaging techniques predict improvements in markers of response following CRT with similar accuracy. However, for CRT candidates with shorter, non-LBBB QRS complexes, a subgroup known to derive less benefit from CRT, CMR may predict those who are more likely to gain both symptomatic and survival benefits.

Influence of pathogens and moderate leukocytes on seminal interleukin (IL)-6, IL-8, and sperm parameters.

PURPOSE: To evaluate the role of pathogens and moderate leukocytes on seminal interleukin (IL)-6, IL-8, and sperm parameters in men undergoing infertility investigation. METHODS: Semen samples from men (n = 171) were divided into three groups on the basis of leukocyte count: no leukocytes (L-; ≤ 0.1 × 10(6)/ml Mio/ml), moderate leukocytes (L ±; >0.1 × 10(6)/ml and <1 × 10(6)/ml), and high leukocytes (=leukocytospermia) (L+; ≥ 1 × 10(6)/ml). Each group was further classified into two subgroups, according to the presence (B+) or absence (B-) of pathogens. IL-6, IL-8, and sperm characteristics were analyzed in each subgroup. A correlation test was performed to show the association between inflammatory parameters and sperm characteristics. RESULTS: No significant differences in leukocyte count, cytokine levels, and sperm characteristics were apparent in subgroups with and without pathogens. Grade b motility was significantly lower in subgroup IIa (L ±,B-) than in subgroup Ia (L-,B-)(p < 0.05). More significant limitations in sperm motility (lower rapid progressive motility and increased percentage of immotile sperm) were observed in subgroup IIIa (L+,B-) compared with subgroup Ia (p < 0.05). Moderate and high leukocytes increased significantly cytokine levels (p < 0.001). CONCLUSIONS: Moderate leukocyte counts could be an indicator of male genital tract inflammation. Seminal pathogens have no influence on cytokine levels and sperm parameters.

Oncostatin M and IL-6 induce u-PA and VEGF in prostate cancer cells and correlate in vivo.

BACKGROUND/AIM: Oncostatin M (OSM) and interleukin-6 (IL-6) are growth factors for prostate cancer (PC). Vascular endothelial growth factor (VEGF) and urokinase-type plasminogen-activator (u-PA) have been implicated in tumour progression. A possible interaction between IL-6, OSM, u-PA and VEGF in PC was investigated. MATERIALS AND METHODS: Primary prostate epithelial cells (PPEC) and DU-145 PC cells were treated with IL-6 or OSM and the effects on u-PA and VEGF expression were studied. Plasma levels of IL-6, OSM, u-PA and VEGF were determined in patients with or without PC. RESULTS: In DU-145 cells, OSM and IL-6 up-regulated u-PA and VEGF significantly. Higher levels of IL-6 and OSM in metastasising PC than in nonmetastasising PC and benign prostatic hyperplasia (BPH) and correlations between IL-6, OSM, u-PA and VEGF were found. CONCLUSION: OSM and IL-6 increase u-PA and VEGF in DU-145 cells but not in PPEC and possibly, by promoting matrix degradation and angiogenesis, could play a role in the pathogenesis of prostate cancer.

New method for differentiating chronic prostatitis/chronic pelvic pain syndrome IIIA from IIIB involving seminal macrophages and monocytes.

OBJECTIVES: To evaluate a new method for differentiating inflammatory from noninflammatory prostatitis using the simple and rapid quantification of seminal macrophages and monocytes. METHODS: Patients affected with chronic pelvic pain syndrome (CPPS) were classified as having the IIIA (n = 11) and IIIB (n = 30) subtypes according to the peroxidase positive leukocyte concentration in semen; 18 healthy individuals served as controls. Seminal inflammatory markers, including polymorphonuclear elastase, interleukin (IL)-6 and IL-8, and numbers of macrophages/monocytes (MMs) per 50 fields of 1000 × magnification (high-power field [hpf]), were determined for all patients. RESULTS: The numbers of MMs/50 hpf correlated significantly with the peroxidase positive leukocyte counts and IL-8, IL-6, and polymorphonuclear elastase levels (all P < .001). Data from the analysis of receiver operating characteristic curves (area under the curve 0.912 ± 0.073; P < .001) showed a sensitivity of 90.9% and specificity of 86.7% at a cutoff value of 5 MMs/50 hpf. The positive and negative predictive value was 71.4% and 96.3%, respectively. The median concentrations of IL-6, IL-8, and elastase in the patients with CPPS with ≥ 5 MMs/50 hpf differed significantly (P ≤ .002) from those in the patients with <5 MMs/50 hpf. CONCLUSIONS: The results of our study have shown that the quantification of seminal macrophages and monocytes is a simple, rapid, and reproducible technique by which to differentiate chronic prostatitis/CPPS IIIA from IIIB.

Myocardial fibrosis predicts appropriate device therapy in patients with implantable cardioverter-defibrillators for primary prevention of sudden cardiac death.

OBJECTIVES: The purpose of this study was to evaluate the association between regional myocardial fibrosis and ventricular arrhythmias in patients with cardiomyopathy. BACKGROUND: Patients with heart failure are at risk of sudden cardiac death (SCD). Current guidelines recommend implantable cardioverter-defibrillator (ICD) devices for a subgroup based on impaired left ventricular function. A significant proportion of devices never discharge, hence a more accurate method for targeting those at risk is desirable. METHODS: We prospectively enrolled 103 patients meeting criteria for ICD implantation for primary prevention of SCD. Cardiac magnetic resonance imaging was performed before device implantation. Regional fibrosis was identified with late gadolinium enhancement (LGE). RESULTS: Median follow-up was 573 days (interquartile range: 379 to 863 days). The LGE identified regional fibrosis in 31 of 61 (51%) patients with nonischemic cardiomyopathy (NICM) and in all 42 patients with ischemic cardiomyopathy (ICM). There was a 29% (9 of 31) discharge rate in the NICM group with LGE compared with a 14% (6 of 42) discharge rate in the ICM group (p = NS). There were no ICD discharges in the NICM group without LGE, which was significantly lower than the rate observed in both the ICM patients (p = 0.04) and the NICM patients with LGE (p < 0.01). Left ventricular ejection fraction was similar in patients with and without device therapy (24 ± 12% vs. 26 ± 8%, p = NS) and those with or without LGE (25 ± 9% vs. 26 ± 9%, p = NS). CONCLUSIONS: Patients with advanced cardiomyopathy and myocardial fibrosis demonstrated by LGE on cardiac magnetic resonance imaging have a high likelihood of appropriate ICD therapy. Correspondingly, absence of LGE may indicate a lower risk for malignant ventricular arrhythmias.

Disproportionate exercise load and remodeling of the athlete's right ventricle.

PURPOSE: There is evolving evidence that intense exercise may place a disproportionate load on the right ventricle (RV) when compared with the left ventricle (LV) of the heart. Using a novel method of estimating end-systolic wall stress (ES-σ), we compared the RV and LV during exercise and assessed whether this influenced chronic ventricular remodeling in athletes. METHODS: For this study, 39 endurance athletes (EA) and 14 nonathletes (NA) underwent resting cardiac magnetic resonance (CMR), maximal oxygen uptake (VO2), and exercise echocardiography studies. LV and RV end-systolic wall stress (ES-σ) were calculated using the Laplace relation (ES-σ = Pr/(2h)). Ventricular size and wall thickness were determined by CMR; invasive and Doppler echo estimates were used to measure systemic and pulmonary ventricular pressures, respectively; and stroke volume was quantified by Doppler echocardiography and used to calculate changes in ventricular geometry during exercise. RESULTS: In EA, compared with NA, resting CMR measures showed greater RV than LV remodeling. The ratios RV ESV/LV ESV (1.40 ± 0.23 vs 1.26 ± 0.12, P = 0.007) and RV mass/LV mass (0.29 ± 0.04 vs 0.25 ± 0.03, P = 0.012) were greater in EA than in NA. RVES-σ was lower at rest than LVES-σ (143 ± 44 vs 252 ± 49 kdyn · cm, P < 0.001) but increased more with strenuous exercise (125% vs 14%, P < 0.001), resulting in similar peak exercise ES-σ (321 ± 106 vs 286 ± 77 kdyn · cm, P = 0.058). Peak exercise RVES-σ was greater in EA than in NA (340 ± 107 vs 266 ± 82 kdyn · cm, P = 0.028), whereas RVES-σ at matched absolute workloads did not differ (P = 0.79). CONCLUSIONS: Exercise induces a relative increase in RVES-σ which exceeds LVES-σ. In athletes, greater RV enlargement and greater wall thickening may be a product of this disproportionate load excess.

One- and two-dimensional estimation of right and left ventricular size and function-comparison with cardiac magnetic resonance imaging volumetric analysis.

BACKGROUND: Estimations of right ventricular (RV) and left ventricular (LV) size and function based on 1D and 2D measures are commonly used. However, their correlation with volumetric analysis methods is not well documented. METHODS: We analysed a series of subjects undergoing CMR (n=30). Contiguous short axis cine imaging was obtained to assess RV and LV volumes and function. Standard short and long axis cine imaging were performed to evaluate linear and planimetric dimensions as well as functional analysis. RESULTS: Linear and planimetric measurements of the RV in standard long and short axis views correlated weakly with standard volumetric measurements (r=0.34-0.73). RV ejection fraction (EF), when calculated from single plane functional analysis correlated only moderately with the volumetric EF (r=0.75, p<0.001). In contrast, estimation of LV volumes, mass and EF by biplane area-length method demonstrated excellent correlation with volumetric data (r=0.89, 0.92 and 0.91, p<0.001 for all). CONCLUSION: Two-dimensional estimations of volume and function correlate well with LV volumetric analysis, but not with RV volumetric analysis. Estimation of RV size and function based on linear or planimetric assumption models should be performed and interpreted with caution.

Combined dyssynchrony and scar imaging with cardiac magnetic resonance imaging predicts clinical response and long-term prognosis following cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) is advocated in advanced heart failure; however, patient selection remains challenging. We examined the utility of multi-sequential cardiac magnetic resonance imaging (CMR) in predicting outcome after CRT. METHODS AND RESULTS: We performed multi-sequential CMR on 40 subjects with cardiomyopathy and advanced heart failure, despite optimized medical therapy. All patients had been recommended for CRT according to accepted clinical guidelines. Patients were defined by CMR as likely responders if they had significant mechanical dyssynchrony (> or =65 ms delay between septal and posterolateral wall contraction on cine imaging), and no transmural scarring of the anteroseptal or posterolateral wall on delayed contrast-enhanced imaging. Clinical composite score was recorded at baseline and 6 months post-CRT. Long-term follow-up (transplant-free survival) was 497 +/- 55 days post-CRT. A clinical response was achieved in 19/26 (73%) of the CMR-predicted responders and 2/12 (17%) of the CMR-predicted non-responders (P < 0.01, chi(2)). The sensitivity of CMR for prediction of clinical response to CRT was 90%, with a specificity of 59%. Transplant-free survival post-CRT was achieved in 88% of the CMR-predicted responders and 58% of the CMR-predicted non-responders (P < 0.05, Kaplan-Meier survival analysis). CONCLUSION: Multi-sequential CMR identifies patients with severe cardiomyopathy who will respond to CRT with a favourable long-term prognosis.

Diagnostic performance of multisequential cardiac magnetic resonance imaging in acute cardiac allograft rejection.

AIMS: We evaluated cardiac magnetic resonance imaging (CMR) as a non-invasive test for cardiac allograft rejection. METHODS AND RESULTS: We performed CMR on 50 heart-transplant recipients. Acute rejection was confirmed in 11 cases by endomyocardial biopsy (EMB) and presumed in 8 cases with a recent fall in left-ventricular ejection fraction (LVEF) not attributable to coronary allograft vasculopathy. Control patients had both normal LVEF and no significant rejection on EMB. Cardiac magnetic resonance imaging evaluated myocardial function, oedema, and early and late post-Gadolinium-DTPA contrast enhancement. Patients with confirmed rejection demonstrated elevated early relative myocardial contrast enhancement (4.1 +/- 0.3 vs. 2.8 +/- 0.2, P < 0.001) and a trend to higher oedema suggested by higher relative myocardial intensity on T(2)-weighted imaging compared to controls (2.1 +/- 0.1 vs. 1.7 +/- 0.1, P = 0.1). With rejection defined as increased early contrast enhancement or myocardial oedema, the sensitivity and specificity of CMR compared with EMB were 100 and 73%, respectively. Eight patients with presumed rejection also had elevated early myocardial contrast enhancement compared with controls, (8.7 +/- 1.9 vs. 2.8 +/- 0.2, P < 0.05), which reduced following increased immunosuppression (8.7 +/- 1.9 vs. 4.6 +/- 1.2, P < 0.05). In these patients LVEF improved following increased immunosuppression (32 +/- 5 vs. 46 +/- 5%, P < 0.05). CONCLUSION: Cardiac magnetic resonance imaging is a promising modality for non-invasive detection of cardiac allograft rejection.

Effect of transdermal electromotive drug therapy on fibrogenic cytokine expression in Peyronie's disease.

OBJECTIVES: To assess the effect of transdermal electromotive drug therapy (EMDT) on transforming growth factor-beta (TGF-beta) and basic fibroblast growth factor (bFGF) expression and their receptors in plaques in patients with Peyronie's disease. METHODS: Tissue was obtained from 13 patients with stable Peyronie's disease who had undergone plaque excision because of penile curvature. Of the 13 patients, 7 underwent EMDT with dexamethasone, verapamil, and lidocaine as first-line therapy before plaque excision and 6 were therapy naive. TGF-beta and bFGF mRNA and protein expression and that of their receptors were measured using real-time polymerase chain reaction and Western blotting. RESULTS: The mean patient age was 52.83 years. The mean interval from the end of EMDT to plaque excision was 7.6 months, with stable disease for >or=5 months. The comparison of TGF-beta mRNA expression in the plaques showed no difference between the EMDT and therapy-naive patients (P = .17). Also, TGF-beta protein expression in the plaques was not significantly different between the EMDT and therapy-naive patients (P = .443). TGF-beta receptor 1 mRNA expression in the plaques was significantly different between the EMDT and therapy-naive patients (P = .023), but no difference was found for TGF-beta receptor 2 mRNA (P = .292). The expression of bFGF mRNA (P = .0005) and bFGF protein expression (P = .034) in the plaques was significantly lower after EMDT. bFGF receptor mRNA expression (P = .619) showed no significant differences. CONCLUSIONS: Patients with Peyronie's had significantly lower bFGF mRNA and bFGF protein expression in the plaques after EMDT. Also, overexpression of TGF-beta protein and the TGF-beta receptor was identified in the EMDT plaques compared with the therapy-naive plaques.

Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping.

OBJECTIVES: The purpose of this study was to investigate a noninvasive method for quantifying diffuse myocardial fibrosis with cardiac magnetic resonance imaging (CMRI). BACKGROUND: Diffuse myocardial fibrosis is a fundamental process in pathologic remodeling in cardiomyopathy and is postulated to cause increased cardiac stiffness and poor clinical outcomes. Although regional fibrosis is easily imaged with cardiac magnetic resonance, there is currently no noninvasive method for quantifying diffuse myocardial fibrosis. METHODS: We performed CMRI on 45 subjects (25 patients with heart failure, 20 control patients), on a clinical 1.5-T CMRI scanner. A prototype T(1) mapping sequence was used to calculate the post-contrast myocardial T(1) time as an index of diffuse fibrosis; regional fibrosis was identified by delayed contrast enhancement. Regional and global systolic function was assessed by cine CMRI in standard short- and long-axis planes, with echocardiography used to evaluate diastology. An additional 9 subjects underwent CMRI and endomyocardial biopsy for histologic correlation. RESULTS: Post-contrast myocardial T(1) times correlated histologically with fibrosis (R = -0.7, p = 0.03) and were shorter in heart failure subjects than controls (383 +/- 17 ms vs. 564 +/- 23 ms, p < 0.0001). The T(1) time of heart failure myocardium was shorter than that in controls even when excluding areas of regional fibrosis (429 +/- 22 ms vs. 564 +/- 23 ms, p < 0.0001). The post-contrast myocardial T(1) time shortened as diastolic function worsened (562 +/- 24 ms in normal diastolic function vs. 423 +/- 33 ms in impaired diastolic function vs. 368 +/- 20 ms in restrictive function, p < 0.001). CONCLUSIONS: Contrast-enhanced CMRI T(1) mapping identifies changes in myocardial T(1) times in heart failure, which appear to reflect diffuse fibrosis.

Utility of myocardial fibrosis and fatty infiltration detected by cardiac magnetic resonance imaging in the diagnosis of arrhythmogenic right ventricular dysplasia--a single centre experience.

INTRODUCTION: Cardiac magnetic resonance imaging (CMR) has evolved as a major diagnostic tool to evaluate arrhythmogenic right ventricular dysplasia (ARVD). However, there is a lack of consensus in the interpretation of findings such as fatty infiltration or myocardial fibrosis. We examined the diagnostic utility of these two features in the diagnosis of ARVD. METHODS: We performed fast imaging employing steady-state acquisition cine imaging, T(1)-weighted black blood imaging with and without fat suppression and post-contrast delayed enhancement on a 1.5-T scanner to evaluate ventricular function and morphology, fatty infiltration and regional myocardial fibrosis in 52 subjects with suspected ARVD. RESULTS: Eight subjects met the international diagnostic criteria for ARVD. Right ventricle (RV) delayed hyper-enhancement was found in 7 of 8 (88%) ARVD subjects compared to 6 of 44 (14%) subjects without ARVD (p<0.001). Fatty infiltration was only identified in 1 ARVD patient, and 1 non-ARVD patient. On multiple logistic regression analysis RV enhancement remained an independent predictor for the diagnosis of ARVD (p<0.05). CONCLUSION: RV delayed enhancement is common in patients with ARVD, whereas detection of fatty infiltration of the right ventricle was rare in our patient population. The inclusion of RV fibrosis on CMR as a feature of ARVD may improve the diagnostic accuracy of this condition.

Effect of antibiotic therapy on interleukin-6 in fresh semen and postmasturbation urine samples of patients with chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVES: To investigate the effect of antibiotic therapy on interleukin (IL)-6 in fresh semen and postmasturbation urine samples of patients with chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS). METHODS: A total of 128 patients with CP/CPPS prospectively underwent the evaluation of IL-6 in fresh semen and postmasturbation urine samples. At 6 weeks after 4 weeks antibiotic therapy, the IL-6 levels were re-evaluated. RESULTS: Of the 128 patients, 109 (85.2%) were available for our analysis. Of the 109 patients, 72 (66.1%) met the criteria for National Institutes of Health (NIH) classification for inflammatory CP/CPPS (type IIIa) and 37 (33.9%) met the NIH criteria for noninflammatory CP/CPPS (type IIIb). Before antibiotic therapy, 86 patients (78.9%), irrespective of NIH classification, had an increased IL-6 level in fresh semen; 64 (88.9%) patients with CP/CPPS type IIIa and 22 (59.5%) with type IIIb CP/CPPS had increased IL-6 levels. After 4 weeks of therapy, a significant reduction was found in the IL-6 level, with only 44 (40.4%, P = .009) patients showing an increased IL-6 level: 34 patients with type IIIa (47.2%, P = .0000) and 10 with type IIIb (27.0%, P = .0033). An increased IL-6 level was found in the postmasturbation urine sample in 37 patients (33.9%), irrespective of NIH classification: 28 (38.9%) with type IIIa and 9 (24.3%) with type IIIb. At 6 weeks after therapy, only 3 patients (2.8%, P = .000) had an increased IL-6 level: 2 with type IIIa (2.8%, P = .0000) and 1 with type IIIb (2.7%, P = .02). CONCLUSIONS: The IL-6 levels had decreased significantly after antibiotic therapy in patients with CP/CPPS, suggesting a bacterial inflammatory character. The determination of IL-6 in seminal plasma and postmasturbation urine samples is useful as an addition to the diagnostic test for the patient with CP/CPPS and as an efficacy marker for therapy.

The effects of intravesical pentosanpolysulfate treatment on the symptoms of patients with bladder pain syndrome/interstitial cystitis: preliminary results.

The objective of the study was to determine whether intravesical pentosanpolysulfate (PPS) reduces symptoms associated with bladder pain syndrome/interstitial cystitis (BPS/IC). In a prospective, uncontrolled, open-label study, 29 female patients with BPS/IC received 300 mg PPS intravesically twice a week for 10 weeks and thereafter a voluntary maintenance therapy once a month. Treatment response was assessed by Visual Analog Scale (VAS) for quality of life and O'Leary-Sant Symptom and Problem Index (OSPI). Patients were tested before treatment, after 5 weeks of treatment, and 1 week, 3, 6, and 12 months after termination of the initial treatment. Twenty-five patients underwent the 10-week treatment and the 3-month follow-up. Mean reduction of VAS/OSPI was from 8.8/26.4 before to 4/15.3 after treatment, 3.8/15.2 after 3 months, 3.8/14 after 6 months, and 3.4/12.1 after 12 months. In 21 patients, renewed instillation or maintenance therapy was necessary. Intravesical treatment with PPS reduces both the VAS and the OSPI in patients with BPS/IC.

Hyaluronan treatment of interstitial cystitis/painful bladder syndrome.

The aim of this study is to evaluate the efficacy of intravesical hyaluronan therapy in interstitial cystitis/painful bladder syndrome (IC/PBS). One hundred twenty-six patients with IC/PBS and an average disease duration of 6.1 years were treated with weekly instillations of a 50-cm3 phosphate-buffered saline solution containing 40 mg sodium hyaluronate. To be eligible for hyaluronan treatment, a positive modified potassium test was requested as a sign of a urine-tissue barrier disorder. Data were obtained by a visual analogue scale (VAS) questionnaire rating from 0 to 10 that asked for global bladder symptoms before and after therapy. Additional questions evaluated the therapeutic impact on quality of life. A positive and durable impact of hyaluronan therapy on IC/PBS symptoms was observed--103 (85%) of the patients reported symptom improvement (> or =2 VAS units). The mean initial VAS score of 8.5 decreased to 3.5 after therapy (p < 0.0001). Out of 121 patients, 67 (55%) remained with no or minimal bladder symptoms after therapy (VAS 0-2). The majority (101, 84%) reported significant improvement of their quality of life. Intravesical therapy had to be initiated again with good success in 43 patients (34.5%) as symptoms recurred after discontinuation of treatment, while the rest stayed free of symptoms for up to 5 years. In general, hyaluronan therapy was well tolerated and, with the exception of mild irritative symptoms, no adverse reactions were reported for a total of 1,521 instillations. Timely hyaluronan instillation therapy may lead to complete symptom remission or even cure in part of the IC/PBS patients, while some responders need continuous intravesical therapy. The present results suggest that selection of patients for hyaluronan therapy by potassium testing improves the outcome of intravesical therapy with a response rate of >80%.

Effect of intravesical glycosaminoglycan substitution therapy on bladder pain syndrome/interstitial cystitis, bladder capacity and potassium sensitivity.

OBJECTIVE: To evaluate changes in bladder capacity and potassium sensitivity after glycosaminoglycan (GAG) substitution therapy. MATERIAL AND METHODS: The study population comprised two groups of female patients with bladder pain syndrome/interstitial cystitis (BPS/IC): responders (those with symptom improvement) and non-responders (those without symptom improvement) after a 10-week period of intravesical, episodic, weekly, GAG substitution therapy. A total of 27 volunteers with increased pre-therapeutic potassium sensitivity were enrolled in the study and re-evaluated using the modified comparative potassium test (maximal bladder capacity with a saline solution versus a 0.2 M KCl solution) following intravesical GAG substitution therapy. RESULTS: In the 13 responders, the average maximal bladder capacity increased by 17% with the saline solution and by 101.5% with the 0.2 M KCl solution. In the 14 non-responders, post-therapeutic average maximal bladder capacity was decreased by 35% with the saline solution and remained relatively unchanged after instillation with a 0.2 M KCl solution. CONCLUSION: These data demonstrate that in patients who respond symptomatically to intravesical GAG substitution therapy, cystometric bladder capacity is increased, whereas non-responders experience a decrease in bladder capacity.