Abstract Background Primary ciliary dyskinesia (PCD) is a heterogenous disease caused by mutations of miscellaneous genes which physiologically play an important role in proper structure and/or function of various cellular cilia including sperm flagella. Besides male infertility, the typical phenotypes, based on decreased mucociliary clearance, are lifelong respiratory issues, i.e., chronic bronchitis leading to bronchiectasis, chronic rhinosinusitis, and chronic otitis media. Moreover, since motile cilia are important during embryological development in the sense of direction of gut rotation, 50% of affected individuals develop situs inversus – so-called Kartagener’s syndrome. Case presentation We present two cases of PCD as a rare cause of male infertility. Conclusions Primary ciliary dyskinesia should be suspected in infertile males having (sub)normal sperm concentration values with persistent zero motility together with patient’s and/or family history of respiratory symptoms like bronchiectasis, chronic cough, rhinitis, recurrent sinusitis, and otitis media. Due to more than 50 identified mutations until now, the causal mechanism of male infertility is miscellaneous and not in all cases known in detail. Besides impaired sperm motility, other mechanisms significantly decreasing efficacy of assisted reproduction techniques play a pivotal role. Thus, proper diagnostic work-up including, among others, sperm DNA fragmentation, is mandatory to avoid ineffective treatment burden.
In developed countries, approximately 15% of couples suffer from infertility, i.e. they do not conceive within one year of a regular unprotected sexual intercourse. Since infertility is the only one diagnosis of a couple, and not of an individual, it is essential to examine the couple as the unit. Sperm analysis, i.e. native microscopic evaluation, has been used for decades as a golden standard for male fertile potential assessment. Sperm analysis, in its fundamental form, has been only morphological, and not functional evaluation of ejaculate, thus it might not give us reliable information about actual fertile potential of an individual male. On that account, new methods are being introduced to the clinical practice with a goal to improve diagnostics and subsequent treatment. The article presents these new methods, namely flow cytometry, and the impact of asymptomatic urogenital infections on fertility.
Kratka Z, Luxova S, Vik V. Využiti průtokove cytometrie pro stanoveni kvality ejakulatu u mužů s poruchou reprodukce. Hlavni stanovisko: Vysetřeni spermiogramem neposkytuje dostatek informaci o kvalitě spermii. Pomoci průtokove cytometrie je možne stanovit zastoupeni apoptotických spermii v ejakulatu, fragmentaci jejich DNA a integritu akrozomu. Tyto testy umožňuji diagnostikovat pacienty s rizikem nižsi fertility, kteři by měli být vysetřeni andrologem. Cil: Přehled výsledků vysetřeni kvality spermii pomoci průtokove cytometrie Soubor pacientů a metody: Vysetřeni ejakulatu bylo provedeno u 800 mužů (ve věku 21-66 let) lecených v Centrech asistovane reprodukce GENNET. Soubor zahrnoval 366 normozoospermiků a 434 pacientů s patologickým spermiogramem. Pomoci průtokove cytometrie byl u vsech pacientů stanoven pocet živých a apoptotických spermii, u 213 pacientů byl stanoven pocet spermii s nizkou integritou akrozomu a u 65 pacientů byl stanoven pocet spermii s fragmentaci DNA metodou TUNEL. Pacienti byli rozděleni do skupiny ApoHigh s vysokým zastoupenim apoptotických spermii (>50 % apoptotických spermii) a ApoLow s nizkým zastoupenim apoptotických spermii (<50 % apoptotických spermii). Výsledky: U normozoospermiků bylo zjistěno 16,9 % ApoHigh vzorků, u pacientů s patologickým spermiogramem 53,9 % ApoHigh vzorků. Cim vice je apoptotických spermii v ejakulatu, tim vyssi je výskyt fragmentace DNA a nizke integrity akrozomu. Průměrna hodnota fragmentace DNA byla vyssi u vzorků ApoHigh než u ApoLow jak u normozoospermiků (24,0 % vs. 13,5 %), tak u pacientů s patologickým spermiogramem (33,3 % vs. 18,0 %). Vyssi průměrný pocet spermii s nizkou integritou akrozomu byl zjistěn u ApoHigh vzorků než u ApoLow jak u normozoospermiků (40,2 % vs. 23,9 %), tak u pacientů s patologickým spermiogramem (53,1 % vs. 35,2 %). Zavěr: Vyssi zastoupeni apoptotických spermii v ejakulatu snižuje jeho kvalitu. Test apoptozy spermii, fragmentace DNA a stanoveni integrity akrozomu doplňuji informace ziskane ze spermiogramu a umožňuji vytipovat rizikove subfertilni pacienty, pro ktere je vhodne podrobne andrologicke vysetřeni.
Novak J, Vik V. Domaci vysetřeni spermiogramu pomoci chytreho mobilniho telefonu? Vitejte v eře telespermatologie. Autor seznamuje ceske ctenaře s možnosti vysetřeni spermiogramu pomoci chytreho mobilniho telefonu.
Human diseases are often diagnosed by determining levels of relevant enzymes and treated by enzyme inhibitors. We describe an assay suitable for both ultrasensitive enzyme quantification and quantitative inhibitor screening with unpurified enzymes. In the DNA-linked Inhibitor ANtibody Assay (DIANA), the target enzyme is captured by an immobilized antibody, probed with a small-molecule inhibitor attached to a reporter DNA and detected by quantitative PCR. We validate the approach using the putative cancer markers prostate-specific membrane antigen and carbonic anhydrase IX. We show that DIANA has a linear range of up to six logs and it selectively detects zeptomoles of targets in complex biological samples. DIANA's wide dynamic range permits determination of target enzyme inhibition constants using a single inhibitor concentration. DIANA also enables quantitative screening of small-molecule enzyme inhibitors using microliters of human blood serum containing picograms of target enzyme. DIANA's performance characteristics make it a superior tool for disease detection and drug discovery.
The effects of aging, magnetic field and the voxel localization on measured concentrations of citrate (Cit), creatine (Cr), cholines (Cho) and polyamines (PA) in a healthy prostate were evaluated.
We report a 50-year-old female patient with a left-sided renal abscess caused by extended-spectrum β-lactamase-producing bacteria. According to the ORENUC classification she had phenotype N. The course was complicated by a perforation to an adjacent cyst and later to the renal pelvis. A primarily conservative approach of intravenous antibiotics had to be changed to an ultrasonography-guided percutaneous drainage of the lesion and insertion of a ureteral stent to stem a high volume of urine leakage. Drainage of a renal abscess is indicated if the size is larger than 3 cm according to EAU guidelines (relative size) or when the resolution does not occur after antibiotics. One-year follow-up showed the patient made a full recovery with no recurrence of a urinary tract infection or of any abscess.
Novak J, Stejskal J, Mokris J, Borovicka V, Vik V, Girsa D, Koukolik F, Zachoval R. Infikovana cysta způsobujici mechanický syndrom jako komplikace renalniho karcinomu. V nasledujici kazuistice demonstrujeme 57leteho pacienta, který se dostavil s cystickým ložiskem prave ledviny způsobujicim mechanický syndrom. Nalez klinicky imponoval jako infikovana cysta, diferencialně diagnosticky nebylo možne vyloucit cysticky změněný renalni karcinom, který byl po radikalnim ledvinu setřicim výkonu histologicky definitivně verifikovan.
BACKGROUNDGlutamate carboxypeptidase II (GCPII) is a transmembrane enzyme that cleaves N-acetyl-L-aspartyl-L-glutamate (NAAG) in the brain. GCPII is highly expressed in the prostate and prostate cancer and might be associated with prostate cancer progression. Another exopeptidase, plasma glutamate carboxypeptidase (PGCP), was reported to be similar to GCPII and to share its NAAG-hydrolyzing activity.METHODSWe performed a radioenzymatic assay with [H-3]NAAG as a substrate to detect and quantify the enzymatic activity of GCPII in plasma. Using a specific antibody raised against native GCPII (2G7), we immunoprecipitated GCPII from human plasma. We also cloned two PGCP constructs, expressed them in insect cells, and tested them for their NAAG-hydrolyzing activity.RESULTSWe detected GCPII protein in human plasma and found that its concentration ranges between 1.3 and 17.2 ng/ml in volunteers not diagnosed with prostate cancer. Recombinant PGCP was enzymatically active but exhibited no NAAG-hydrolyzing activity.CONCLUSIONGCPII is present in human blood, and its concentration within a healthy population varies. Recombinant PGCP does not hydrolyze NAAG, suggesting that GCPII alone is responsible for the NAAG-hydrolyzing activity observed in human blood. The potential correlation between GCPII serum levels and the disease status of prostate cancer patients will be further investigated. Prostate 74:768-780, 2014. (c) 2014 Wiley Periodicals, Inc.
Background: Storage symptoms are often undertreated in men with lower urinary tract symptoms (LUTS).Objective: To evaluate the combination of an antimuscarinic (solifenacin) with an alpha-blocker (tamsulosin) versus tamsulosin alone in the treatment of men with LUTS.Design, setting, and participants: A double-blind, 12-wk, phase 2 study in 937 men with LUTS (>= 3 mo, total International Prostate Symptom Score [IPSS] >= 13, and maximum urinary flow rate 4.0-15.0 ml/s).Intervention: Eight treatment groups: tamsulosin oral controlled absorption system (OCAS) 0.4 mg; solifenacin 3, 6, or 9 mg; solifenacin 3, 6 or 9 mg plus tamsulosin OCAS 0.4 mg; or placebo.Outcome measurements and statistical analysis: The primary efficacy end point was change from baseline in total IPSS. Secondary end points included micturition diary and quality-of-life (QoL) parameters. Post hoc subgroup analyses were performed by severity of baseline storage symptoms, with statistical comparisons presented only for tamsulosin OCAS alone versus combination therapy, due to the small sample size of the solifenacin monotherapy and placebo subgroups.Results and limitations: Combination therapy was associated with significant improvements in micturition frequency and voided volume versus tamsulosin OCAS alone in the total study population; improvements in total IPSS were not significant. Statistically significant improvements in urgency episodes, micturition frequency, total urgency score, voided volume, IPSS storage subscore, IPSS-QoLindex, and Patient Perception of Bladder Condition were observed in a subpopulation of men with two or more urgency episodes per 24 h (Patient Perception of Intensity of Urgency Scale grade 3 or 4) and eight or more micturitions per 24 h at baseline (storage symptoms subgroup) with combination therapy versus tamsulosin OCAS alone (p <= 0.05 for the dose-response slope, all variables). Combination therapy was well tolerated, and adverse events were consistent with the safety profiles of both compounds.Conclusions: Solifenacin plus tamsulosin OCAS did not significantly improve IPSS in the total study population but offered significant efficacy and QoL benefits over tamsulosin OCAS monotherapy in men with both voiding and storage symptoms at baseline. Combination therapy was well tolerated.ClinicalTrials.gov identifier: NCT00510406 (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.
AimsTo evaluate the potential of mirabegron, a selective 3-adrenoceptor agonist, for treatment of overactive bladder (OAB) symptoms.MethodsA multicenter, randomized, double-blind, double-dummy, parallel group, placebo and active-controlled, Phase 2, proof-of-concept study was conducted. Eligible patients (n=314) were enrolled into a single-blind, 2-week placebo run-in period followed by a randomized, double-blind, placebo-controlled treatment period. Patients received mirabegron 100 or 150mg twice-daily (BID), placebo or tolterodine 4mg extended release (ER) once-daily for 4 weeks. Primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes per 24hr. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes per 24hr; severity of urgency; nocturia, and quality of life measures. Safety parameters included adverse events, laboratory tests, electrocardiogram parameters and post-void residual volume.ResultsMirabegron 100 and 150mg BID resulted in a statistically significant improvement versus placebo in mean change from baseline to end-of-treatment in the primary endpoint of micturition frequency (2.2micturitions/24hr vs. 1.2micturitions/24hr for both doses, adjusted P0.01 for both comparisons). Mirabegron had a statistically significant effect versus placebo for most secondary endpoints, including quality of life variables. Despite a small increase in pulse rate, mirabegron demonstrated good safety and tolerability.ConclusionsMirabegron was efficacious and well tolerated in patients with OAB symptoms and heralds the first of a new class of oral pharmacological therapy for OAB for more than 30 years. Neurourol. Urodynam. 32:1116-1122, 2013. (c) 2013 Wiley Periodicals, Inc.
British Journal of UrologyVolume 81, Issue 1 p. 173-174 Invasive carcinoma in bladder exstrophy with transitional, squamous and mucus-producing differentiation Vik, Vik The Institute of Urology and Nephrology, University College London Medical School, London, UKSearch for more papers by this author Gerharz, Gerharz The Institute of Urology and Nephrology, University College London Medical School, London, UKSearch for more papers by this author Woodhouse, Woodhouse The Institute of Urology and Nephrology, University College London Medical School, London, UKSearch for more papers by this author Vik, Vik The Institute of Urology and Nephrology, University College London Medical School, London, UKSearch for more papers by this author Gerharz, Gerharz The Institute of Urology and Nephrology, University College London Medical School, London, UKSearch for more papers by this author Woodhouse, Woodhouse The Institute of Urology and Nephrology, University College London Medical School, London, UKSearch for more papers by this author First published: 25 December 2001 https://doi.org/10.1046/j.1464-410x.1998.00330.xCitations: 6 Mr Woodhouse The Institute of Urology and Nephrology, University College London Medical School, 48 Riding House Street, London W1P 7PN, UK. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume81, Issue1January 1998Pages 173-174 RelatedInformation