Martin Ludwig

Evaluation of the cytokines interleukin 8 and epithelial neutrophil activating peptide 78 as indicators of inflammation in prostatic secretions.

OBJECTIVES Chronic prostatitis/chronic pelvic pain syndrome (CPPS) is a disorder characterized by pelvic pain and varying degrees of inflammation exhibited in expressed prostatic secretions (EPS). To provide objective parameters of inflammation, we measured the cytokines interleukin 8 (IL-8) and epithelial neutrophil activating peptide 78 (ENA-78) in EPS of healthy men, men with benign prostatic hyperplasia (BPH), men with bacterial prostatitis (BP), and men with chronic prostatitis/CPPS. METHODS Enzyme-linked immunosorbent assays of the EPS for IL-8 and ENA-78 were done in 63 men: control (n = 9), BPH (n = 6), BP (n = 3), inflammatory CPPS (National Institutes of Health [NIH] category IIIa) (n = 17), noninflammatory CPPS (NIH category IIIb) (n = 17), and asymptomatic inflammatory prostatitis (NIH category IV) (n = 11). RESULTS IL-8 was detectable in all patients, and ENA-78 was detectable in all except 2 patients (threshold of detection 10 pg/mL for IL-8, 15 pg/mL for ENA-78). Mean levels of IL-8 [ENA-78] were similar in control (3010 pg/mL [423 pg/mL]), BPH (3341 pg/mL [98 pg/mL]), and IIIb (2751 pg/mL [335 pg/mL]) groups. Both cytokine levels were higher in BP (11,175 pg/mL [13,761 pg/mL]), IIIa (10,418 pg/mL [2240 pg/mL]), and IV (8571 pg/mL [1865 pg/mL]) groups. A statistically significant difference between the control group versus BP, IIIa, and IV (P <0.05) groups was found for IL-8 but not for ENA-78. CONCLUSIONS IL-8 and ENA-78 are frequently elevated in the EPS of men with BP, CPPS IIIa, and asymptomatic inflammatory prostatitis category IV. These cytokines are direct mediators of leukocyte accumulation and activation at inflammatory sites and may be responsible, in part, for the presence of inflammatory reaction in the prostate.

A Pollen Extract (Cernilton) in Patients with Inflammatory Chronic Prostatitis–Chronic Pelvic Pain Syndrome: A Multicentre, Randomised, Prospective, Double-Blind, Placebo-Controlled Phase 3 Study

BACKGROUND National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists. OBJECTIVES To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS. DESIGN, SETTING, AND PARTICIPANTS We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres. INTERVENTION Participants were randomised to receive oral capsules of the pollen extract (two capsules q8h) or placebo for 12 wk. MEASUREMENTS The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post-prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk. RESULTS AND LIMITATIONS In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract (n=70) or placebo (n=69). The individual domains pain (p=0.0086) and quality of life (QoL; p=0.0250) as well as the total NIH-CPSI score (p=0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% (p=0.0141), respectively. Adverse events were minor in all patients studied. CONCLUSIONS Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.

Diagnosis and therapeutic management of 18 patients with prostatic abscess

OBJECTIVES Our retrospective study aimed to analyze the findings and therapeutic strategies in 18 men who were admitted to our department as outpatient emergency cases with prostatic abscess. METHODS During the period 1985 to 1997, prostatic abscess was diagnosed in 18 patients (mean age 48 years, range 20 to 68) on the basis of evidence of fluctuation at digital rectal examination and transrectal ultrasound (TRUS) findings. Diagnostic workup included analysis of midstream urine and abscess fluid for leukocytes and pathogens. Therapeutic options were conservative treatment and/or draining procedures. RESULTS Predisposing diseases were found in 13 men. Fluctuation at digitorectal palpation was present in 15 patients. In 3 patients, diagnosis was based on TRUS. All men demonstrated leukocytes in their midstream urine. Causative pathogens in midstream urine were found in 11 patients. In 3 men, additional microbiologic evaluation of abscess fluid revealed uncommon pathogens. All patients received antibiotic treatment. Nine men with monofocal abscess less than 1 cm in diameter were treated with antibiotic therapy and a suprapubic catheter. Surgical drainage (transperineal or transrectal puncture, partly guided by TRUS, or transurethral unroofing) was performed in 12 patients and included 3 patients in whom conservative treatment failed. CONCLUSIONS Our data confirm the importance of predisposing factors in the pathogenesis of prostatic abscess. Medical history and analysis of midstream urine indicated a diagnosis that was confirmed by digital palpation. In some cases, TRUS may improve diagnosis and treatment. Although both operative and conservative therapy strategies appear feasible, prostatic abscess chiefly requires individually selected drainage procedures.

Influence of different uropathogenic microorganisms on human sperm motility parameters in an in vitro experiment

Summary. The influence of different uropathogenic microorganisms (E. coli, enterococcus, Pseudomonas aeruginosa, Staphylococcus saprophyticus, Candida albicans) on human sperm motility was studied in vitro with a computer‐assisted sperm analyser (CASA).

Outcome of antibiotic therapy with ciprofloxacin in chronic bacterial prostatitis

Chronic bacterial prostatitis (CBP) is a rare infection of the prostate with Escherichia coli being the predominant causative pathogen. Appropriate antimicrobial therapy is mandatory for cure. We report on our experience with a 4-week regimen of ciprofloxacin in 40 men suffering from CBP due to E. coli. Follow-up was conducted over a period of 12 to 24 months. The microbiological work-up included an analysis of expressed prostatic secretions (EPS) and semen.Eradication of the pathogen in EPS was achieved in 92% of patients 3 months after therapy and in about 70 to 80% of patients evaluated 12 and 24 months after treatment, respectively. Treatment failure was not associated with the presence of prostatic calculi, as assessed by transrectal ultrasonography. After successful therapy, mean EPS pH decreased significantly from 7.95 to 7.35. Significant bacteriospermia with E. coli was detected in 21/22 (95.5%) patients before treatment and in 6/22 (27.3%) patients 6 months after therapy.Our data reconfirm ciprofloxacin as an excellent antimicrobial agent in the therapy of CBP. However, eradication of the pathogen is unpredictable and cannot be achieved in every case. Further studies should correlate microbiological treatment success with symptomatic relief, as assessed by standardised questionnaires.

Extracorporal Shock Wave Therapy in the Treatment of Peyronie’s Disease

Objective: To test whether extracorporal shock wave therapy (ESWT) has an effect in the treatment of Peyronie’s disease.Methods: 22 patients with Peyronie’s disease and previous unsuccessful oral drug therapy were treated with ESWT in a prospective design with a follow–up of at least 3 months; 23 age–matched patients without previous therapy received oral placebo drug for 6 months daily as control. The standard follow–up included palpation, ultrasound, autophotography and evaluation of symptomatology based on a symptom score. The shock waves were applied under ultrasound guidance using the ‘Storz Minilith SL1’ lithotripter.Results: The results show a significant decrease in penile curvature in the patients treated with ESWT. Concerning the decrease in pain, subjective improvement and improvement in the quality of sexual intercourse, there was no significant difference to the case–control group. The inhomogeneity of the 2 groups may influence these results due to the questionable varying natural history.Conclusions: A prospective, controlled multicenter study with standardized parameters (concerning technique and patients) is urgently required to test the effect of ESWT.

Evaluation of seminal plasma parameters in patients with chronic prostatitis or leukocytospermia

Summary. Though detailed cytological and microbiological diagnostic procedures are routinely carried out in male genital tract infection, the correct diagnosis and localization of inflammation or infection is often difficult. In this prospective study, the relevance of the seminal plasma markers PMN elastase, complement C3, CRP, fructose, PSP 94, PSA, and α‐glucosidase was investigated in 13 patients with chronic prostatitis, 31 patients with significant leukocytospermia, and 58 patients with non‐inflammatory diseases (controls). Statistically relevant results were obtained for PMN elastase when comparing chronic prostatitis with controls, leukocytospermia with controls (P<0.001) and chronic prostatitis with leukocytospermia (P<0.05); for complement C3 chronic prostatitis and leukocytospermia vs. controls (P<0.05) and for fructose/ejaculate leukocytospermia vs. controls (P<0.05). No statistically relevant differences were found for C‐reactive protein, α‐glucosidase, PSA and prostatic secretory protein (PSP 94). To delimit genital tract inflammation from non‐inflammatory patients, cutpoint levels for PMN elastase of 230 ng ml−1 and for C3c of 0.01 g l−1 were suggested. PMN elastase was shown to possess the strongest discriminating power. The assessment of a cutpoint for fructose to indicate seminal vesicle dysfunction is not possible as the significance level is weak (P<0.05).

Comparison of expressed prostatic secretions with urine after prostatic massage—a means to diagnose chronic prostatitis/inflammatory chronic pelvic pain syndrome

OBJECTIVES To compare the analysis of urine after prostatic massage (VB3) with expressed prostatic secretions (EPS) to assess the significance of leukocyte analysis in VB3 and to give a first hint of the diagnosis of inflammatory chronic pelvic pain syndrome (CPPS) when EPS cannot be obtained. METHODS Three hundred twenty-eight men (mean age 38 years, range 18 to 70) with expressible prostatic secretions were investigated. EPS were stained using the Papanicolaou stain and analyzed for leukocytes per high power field (HPF) (x1000). Additionally, identical aliquots of first voided urine (VB1), midstream urine (VB2), and VB3 were centrifuged, stained (Papanicolaou), and analyzed for leukocytes (x400). Patients with increased numbers of leukocytes in VB1 and VB2 (2 or more per x400) were excluded. For statistical analysis, Spearmans correlation coefficient for nonparametric tests was used. RESULTS Of 180 men with less than 10 leukocytes per HPF in EPS, 178 (98.9%) had less than 10 leukocytes per view field in VB3. In 148 men with 10 or more leukocytes per HPF in EPS, 136 (91.9%) also had elevated leukocyte counts in VB3. The presence of elevated leukocytes in VB3 predicted the presence of increased leukocytes in EPS with a high certainty: 91.9% sensitivity, 98.9% specificity, and 95.7% accuracy, with a positive and negative predictive value of 98.6% and 93.7%, respectively. CONCLUSIONS We conclude that the determination of leukocytes in VB3 is a feasible and reliable method compared with the analysis of EPS. However, although this association does not directly prove the significance of VB3 in those patients from whom no EPS can be obtained, we suggest this method be taken into account as an indirect indicator in the diagnosis of inflammation.

Chlamydial antibodies in semen: search for "silent" chlamydial infections in asymptomatic andrological patients.

SummaryThe importance of a serological diagnostic workup in male genitourinary infections withChlamydia trachomatis and its relevance for male infertility is still under debate. In a prospective study, antichlamydial serum and seminal plasma antibodies of 131 consecutive patients (mean age 31: 20–57) without evidence of acute urethritis and with negative urethral chlamydial culture were investigated. The antibody determination was carried out with a genus specific rELISA. In patients with positive seminal plasma IgA, chlamydial genome was evaluated by polymerase chain reaction (PCR). The results were associated with standard semen parameters according to evaluated WHO guidelines. Specific serum IgG antibodies were found in 51 patients (38.9%), IgA in in 39 (29.7%); both antibodies were present in 25 patients (19%). Seminal plasma IgG was demonstrable in seven patients (5.3%), IgA in 26 (19.9%), and five patients were positive for both antibody classes (3.8%). Of the 26 men positive for specific seminal plasma IgA antibodies 12 did not demonstrate a serum antibody reaction. Only two patients with positive IgA titers in their seminal plasma showed a positive chlamydial genome reaction in PCR (8%). Men with antichlamydial seminal plasma IgA and/or IgG did not differ significantly in any of the standard semen sperm parameters from men testing negative for antibodies, with the exception of peroxidase positive leukocytes (p<0.01), nor was there an association between any of the ejaculate parameters and any of the antibody titers. The data of about 40% antichlamydial serum antibody findings without a significant association with seminal plasma antibodies and no clinical signs of infection seem to reflect a history of urogenital infection. The unique presence of seminal plasma IgA in 12 of 26 cases may be caused by a local antibody response due to a “silent” infection. Thus, seminal plasma IgA was associated with signs of inflammation, whereas, there was no association with genome or pathogen demonstration. Therefore, it appears to be necessary to reevaluate genus-specific seminal plasma IgA antibodies with a species-specific microimmunofluorescence test and to compare these results with a genome screening using PCR orin situ hybridization.ZusammenfassungDie Relevanz einer serologischen Diagnostik in der Abklärung männlicher Genitalinfektionen mitChlamydia trachomatis und ihre Bedeutung für die männliche Infertilität ist unklar. In einer prospektiven Studie untersuchten wir Serum- und Seminalplasmaantikörper gegenC. trachomatis von 131 konsekutiven Patienten (31: 20–57 Jahre) ohne Hinweis für eine akute Urethritis mit negativer urethraler Chlamydienkultur. Die Antikörperbestimmung wurde mit einem genusspezifischen r-ELISA durchgeführt. Bei Patienten mit positiven Seminalplasma-IgA wurde ein PCR-Nachweis auf Chlamydiengenom durchgeführt. Die Befunde wurden mit Standard-Ejakulatparametern nach WHO-Kriterien verglichen. Serum-IgG-Antikörper fanden sich bei 51 Patienten (38,9%), Serum-IgA-Antikörper bei 39 Männern (29,7%), beide Antikörper bei 25 Patienten (19%). Seminalplasma-IgG wurde bei 7 (5,3%), IgA bei 26 Patienten (19,9%), beide Antikörper bei fünf Männern (3,8%) nachgewiesen. Von den 26 Männern mit positiven Seminalplasma-IgA-Titern wiesen 12 keine Serum-IgA-Antikörper auf. Nur zwei der Patienten mit positiven Seminalplasma-IgA-Titern zeigten eine positive Chlamydien-PCR (8%). Männer mit Seminalplasma-IgA und/oder IgG-Antikörpern unterschieden sich bezogen auf die Standard-Ejakulatparameter nicht signifikant von Patienten ohne Antikörper. Einzige Ausnahme war der vermehrte Nachweis von paroxidase-positiven Leukozyten (p<0,01). Es fand sich auch keine Assoziation zwischen den einzelnen Ejakulatparametern und der Höhe der Antikörpertiter. Der Nachweis von etwa 40% Chlamydienantikörpern im Serum ohne Assoziation zu Seminalplasmaantikörpern und ohne Zeichen einer klinischen Infektion scheinen eine urogenitale Infektionsanamnese widerzuspiegeln. Der alleinige Nachweis von Seminalplasma-IgA bei 12 von 26 Fällen ist eventuell durch eine lokale Antikörperreaktion bei klinisch inapparenter Infektion zu erklären. Entsprechend fand sich auch eine Assoziation zwischen Seminalplasma-IgA und Entzündungszeichen, während eine Assoziation zum Genom- oder Erregernachweis nicht nachgewiesen werden konnte. Es erscheint uns daher notwendig, die Bedeutung genusspezifischer Seminalplasma-IgA-Antikörper mit einem Spezies-spezifischen Mikroimmunfluoreszenztest zu reevaluieren und diese Befunde mit einem Genomscreening mittels PCR oderin situ Hybridisierung zu überprüfen.

Influence of urogenital infection on sperm function.

Male accessory sex gland infections are considered to be hazards to male fertility. Various pathophysiologic concepts have evolved from experimental and clinical studies that begin to explain the effects of bacteria and immunologic events on spermatozoa. Recent studies have identified and evaluated mediators that are responsible for specific molecular processes in infections that particularly affect the function of spermatozoa.