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— från internationella workshops och medicinska tidskrifter —
På den här sidan kommer jag att lägga in ett antal korta artiklar av vetenskaplig karaktär, som belyser kronisk prostatit ur olika synvinklar.
Classification and Definition of Prostatitis, National Institutes of Health, USA. The following classifications were approved by the working group chairs and will be the NIDDK reference standard for research studies on these diseases and disorders: 1. Acute bacterial prostatitis is an acute infection of the prostate. 2 Chronic bacterial prostatitis is a recurrent infection of the prostate. 3. Chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS), where there is no demonstrable infection. Subgroups of this class are: 3A. Inflammatory
chronic pelvic pain syndrome, where white cells are found in the semen expressed
prostatic secretion 3B. Non-inflammatory chronic pelvic pain syndrome where white cells are NOT found in semen, EPS and VB-3. 4. Asymptomatic
inflammatory prostatitis (AIP), where there are no subjective symptoms but white
blood cells are Hämtat från http://www.prostatitis.org/newdf.html
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New Classification for pelvic pain syndrome? Nedanstående är ett sammandrag av det viktigaste från the Journal of Urology. Vol. 175, 1989-1990, June 2006. A New Classification is Needed for Pelvic Pain Syndromes-Are Existing Terminologies of Spurious Diagnostic Authority Bad for Patients? http://www.jurology.com/issues/contents and then click Previous Issue button Dr. Abrams P, Baranowski A, Berger RE, Fall M, Hanno P, Wesselmann U. We propose that a new nomenclature be introduced for all sufferers of chronic pelvic pain under the umbrella term of chronic pelvic pain syndrome. Within the pelvic pain syndrome a group of sufferers would be identified according to the primary organ that appears to be affected on clinical grounds, for example the prostate or the bladder. In the case of the prostate all symptomatic patients would be said to be suffering from painful perineal prostate syndrome. To arrive at the diagnosis of prostate pain syndrome the prostate would have to be tender, and appropriate sexual and urinary symptoms would be present. A substantial number of patients would have idiopathic painful prostate syndrome when no cause could be identified. To arrive at more specific terms, abnormal inflammatory parameters and/or infection would need to be identified from prostatic secretions or tissue to justify the term prostatitis (acute, chronic or abacterial). However, pain not associated with an individual organ would be described in terms of the symptoms. Many patients can not localize pain origin. Furthermore, even clinical examination can be misleading, as the finding of local tenderness needs to take into account the fact that many patients appear to have generalized trigger points but local tenderness may not indicate a local problem. When in doubt a descriptive approach needs to be used. There are several major advantages to patients of our proposed classification. The affected organ would be specified in clear terms when possible, and the known cause, if any, would be stated. However, more importantly, those patients with no apparent cause for their symptoms could be identified and classified by the symptoms and the organ principally affected. Patients become frustrated and may believe their doctor to be unhelpful at best or incompetent at worst. In our view, telling a patient that the clinician does not fully understand their condition is vital in allowing the patient to have realistic expectations of treatments. Although we do not know the etiology and mechanisms of the pain that these patients perceive, we do have treatments that will help them. Patients need reassurance that symptomatic treatment will improve quality of life, which is another reason why clearly defining the symptoms in this group of patients is important. By explicitly diagnosing some cases as idiopathic, and scrutinizing and compiling constellations of signs and symptoms, research efforts can be concentrated to understand the pathophysiology and thereby develop rational treatments for each subset. Our plea is for the use of a simple descriptive based classification that will be intelligible not only to patients, but also to their care givers.
Understanding chronic pelvic pain syndrome, Norge och Tyskland Urol 2002 Jan;12(1):63-7 Bjerklund Johansen
TE, Weidner W. a) Urology Section, Telemark Central Hospital, Porsgrunn, and
University of Patients with non-inflammatory chronic pelvic pain syndrome, the largest group of prostatitis patients according to the US National Institute of Diabetes and Digestive and Kidney Diseases classification, are characterized by the absence of objective findings. Nothing thus links the symptoms of this disease to the prostate or other male organs in particular. For this reason, observations on interstitial cystitis in women are of interest to understand the chronic pelvic pain syndrome. New information from studies on the inflammatory response in expressed prostatic secretion in patients with chronic pelvic pain syndrome and in bladder tissue from patients with interstitial cystitis indicates that complex systems on the cytokine gene expression level may be operating in these diseases. Research findings point to a common denominator at the level of molecular biology that might explain how the symptoms of chronic pelvic pain syndrome and interstitial cystitis can be precipitated by pathogens, inflammatory reactions and even neurological mechanisms. The initial clinical trial reports of drugs that modulate the inflammatory response in interstitial cystitis are met with great interest. PMID: 11753136 [PubMed - in process]
Granulomatous prostatitis linked to HLA-DRB1*1501 Journal of Urology. 171(6, Part 1 of 2):2326-2329, June 2004. ALEXANDER, RICHARD B. *; MANN, DEAN L.; BORKOWSKI, ANDREW A.; FERNANDEZ-VINA, MARCELO; KLYUSHNENKOVA, ELENA N.; KODAK, JAMES; PROPERT, KATHLEEN J.; KINCAID, MARCIE Abstract: Purpose: Granulomatous prostatitis is characterized by a pattern of granulomatous inflammation in the prostate. In most cases the etiology is unknown. Based on the hypothesis that granulomatous prostatitis may be an autoimmune disease we performed intermediate and selective high resolution typing of HLA-DR in a group of patients with the disease and compared the frequency of class II HLA phenotypes to that in a control group of volunteer marrow donors in the military. Materials and Methods: Histological records from 1 institution from 1990 to 2000 revealed 12 patients with diffuse granulomatous prostatitis. Three patients were dead and 1 refused blood drawing. Peripheral blood from the remaining 8 patients was typed along with blood from an additional 3 identified at the practice of one of us from 1999 through 2002. All slides were reviewed by 1 pathologist. Intermediate resolution typing of HLA-A, B and DR was performed by polymerase chain reaction-sequence specific oligonucleotide probe. High resolution, allele specific identification of HLA DR15 was performed if patients were DR15 positive by intermediate resolution typing. Results: There were 3 black and 8 white individuals identified with diffuse nonspecific granulomatous prostatitis. Six of 8 white patients (75%) were HLA-DR15 by intermediate resolution typing. One of the 3 black American patients (33%) was HLA-DR15. In the control group 127 of 451 white (28.2%) and 23 of 89 black (25.8%) volunteer marrow donors were HLA-DR15. The case-control comparison of white patients was significantly different (Fisher's exact test p = 0.0086). There were no statistically significant differences between case-control comparisons for any other HLA-DR phenotype. High resolution DR15 typing showed that the white patients were HLA-DRB1*1501 and the black patient was HLA-DRB1*1503. Conclusions: The data suggest an association between HLA-DRB1*1501 and granulomatous prostatitis. HLA-DR15 is strongly associated with other autoimmune diseases, notably multiple sclerosis. The data are consistent with an autoimmune etiology for nonspecific granulomatous prostatitis.
Diagnosis of mastocytosis: value of cytochemistry and immunohistochemistry. Hematopathology/Hilton 1020, Mayo Clinic, 200 First Street, Southwest, Rochester, MN 55905, USA. li.chinyang@mayo.edu The diagnosis of mastocytosis or mast cell disease may be difficult sometimes because of the wide variety of clinical presentation, abnormal morphology of mast cells, and variation in histologic features which may mimic varieties of other diseases. Over the years, several cell type specific cytochemical and immunochemical markers have been used for the identification of hematopoietic cells in order to establish the accurate diagnosis of mastocytosis and their associated hematologic diseases. Cytochemical stain for aminocaproate esterase is the most specific enzyme marker for identification of mast cells on cytologic specimens and the immunohistochemical stain for tryptase and/or c-kit has also been established as a sensitive and specific marker for mast cells in paraffin sections. Se även: http://www.b-p-s-a.org.uk/mast_cells_and_ic.htm
J Urol 2002 Jan;167(1):137-40 Mehik A, Hellstrom P, Nickel JC, Kilponen A, Leskinen M, Sarpola A, LukkarinenO. Division of Urology, Department of Surgery, Oulu University Hospital, Oulu, Finland. PURPOSE: We performed a prospective study to confirm early results implying that intraprostatic tissue pressure is elevated in men with the chronic prostatitis-chronic pelvic pain syndrome. We planned to determine further whether this technique would detect a significant difference in inflammatory and noninflammatory categories IIIA and IIIB. MATERIALS AND METHODS: A total of 48 patients with the chronic prostatitis-chronic pelvic pain syndrome, including 18 with inflammatory category IIIA and 30 with noninflammatory category IIIB disease, and 12 asymptomatic controls completed a Finnish version of the National Institutes of Health-Chronic Prostatitis Symptom Index. In addition, culture and microscopy of lower urinary tract segmented specimens, serum prostate specific antigen determination, transrectal ultrasound, uroflowmetry and ultrasound post-void residual urine measurement were done. All patients and controls also underwent independent intraprostatic right and left lobe tissue pressure measurement using a standard intracompartmental tissue pressure monitor system. Pressure was measured via an intraprostatic needle placed percutaneously in the perineum at baseline, and 10, 60 and 120 seconds after standard saline injection. RESULTS: All patients with the chronic prostatitis-chronic pelvic pain syndrome had significantly higher pressure at all measurement points compared with controls (p <0.001). Mean intraprostatic tissue pressure was significantly higher (p <0.01) in category IIIA with greater than 10 leukocytes per high power field in prostate specific specimens compared with category IIIB with less than 10. CONCLUSIONS: Our study supports the suggestion that patients with the chronic prostatitis-chronic pelvic pain syndrome have significantly higher prostate tissue pressure than controls. Findings also validated the previous clinical assumption that there is a rationale for differentiating chronic prostatitis-chronic pelvic pain syndrome cases into inflammatory and noninflammatory categories. PMID: 11743292 [PubMed - in process]
Jin-Kwan Jeong, Yong-Jin Kim, Ji-Kan Ryu, Kwoan-Youb Choo, Shuguang Piao, Yeonsook Moon, Do-Hwan Seong, In-Young Hyun, Wonsick Choe, Jun-Kyu Suh*, Incheon, Republic of Korea These Korean researchers used a new technique to detect deep-seated infections, called technetium-99(Tc-99) ciprofloxacin imaging, to look for bacterial infection in seminal vesicles in men diagnosed with CP/CPPS. They identified 50 men with CP/CPPS who showed evidence of seminal vesicle infection and compared their symptom scores, four-glass test results, and bacterial cultures with those of 8 men with CP/CPPS who did not show evidence of infection. The researchers tested aspirated seminal vesicle fluid as well as the fluids obtained in the four-glass test. In 17 of the 50 patients who showed "hot uptake" of the imaging medium in seminal vesicles, the researchers found microorganisms in their seminal vesicle fluid, most commonly Escherichia coli (in 13), followed by coagulase-negative staphylococci (in 2), E coli and Enterococcus fecalis (in 1), and Chlamydia trachomatis (in 1). The researchers found no microorganisms in any of the patients who didn't show evidence of uptake on the scans. The investigators concluded that seminal vesicle infection definitely occurs in some men with CP/CPPS, although the impact of that on the diagnosis and treatment remains to be researched.
Value of semen culture in the diagnosis of chronic bacterial prostatitis: A simplified method Scandinavian Journal of Urology and Nephrology, September 2006 , pages 326 - 331 Alberto Budía; José Luis Palmero; Enric Broseta; Susana Tejadillos; Antonio Benedicto; José A. Queipo; Miguel Gobernado; J. Fernando Jiménez Cruz. Departments of Urology, Statistics and Microbiology, "La Fe" University Hospital. Valencia. Spain. Abstract. Objective: To investigate the role of semen cultures versus segmented urine cultures for the diagnosis of bacterial chronic prostatitis. Material and methods: We retrospectively examined 895 patients (age range 17-67 years) who met the consensus criteria for clinical chronic prostatitis/chronic pelvic pain syndrome, 50.1% of whom had dysuria and/or perineal discomfort, 37.4% infertility of unknown etiology and 12.5% erectile dysfunction. Segmented urine cultures, including expressed prostatic secretions (EPSs) and semen culture, were performed in all patients. Results: Of the 895 patients, 182 had significant positive cultures for Gram-negative microorganisms (Escherichia coli was the commonest specimen isolated: 70.4% of cases) and 283 had significant positive cultures for Gram-positive microorganisms. We compared the culture yield in EPS and/or the urine voided after prostatic massage (VB3) sample (four-glass method) with that of the semen sample. In the Gram-negative group, 32 patients were diagnosed by means of semen culture (negative EPS and/or VB3 sample) and in only five cases was a positive diagnosis made despite a negative semen culture (positive EPS and/or VB3 sample). In the remaining subjects, diagnosis was performed with the aid of both EPS/VB3 sample and semen (both of which were positive). In the Gram-positive group, there was significant growth of such microorganisms in semen in every case considered positive, but in only 46 cases was diagnosis achieved via EPS and/or VB3 sample. A diagnosis of chronic prostatitis by Gram-positive microorganisms in these patients was only considered when the same microorganism was retrieved in repeated cultures without previous treatment. Only three cases met such criteria (all of whom had negative EPSs). To evaluate the diagnostic efficiency of the semen and EPS samples, we analyzed their sensitivity and specificity, obtaining higher sensitivity in semen than EPS samples for significant Gram-negative cultures: 97% vs 82.4%. In significant Gram-positive cultures, the sensitivity of semen samples was 100%, compared to only 16.1% for EPS. Conclusions: A semen sample has higher sensitivity than an EPS for the diagnosis of bacterial chronic prostatitis. In our clinical work-up, first-void urine and a semen culture are considered the only tests necessary to diagnose chronic prostatitis. Hela artikeln fins på http://www.informaworld.com/smpp/content~content=a755317687?words=prostatitis&hash=2387638923
Keith Jarvi*, Mount Sinai Hospital, Toronto Canada; Wenjun Wang, Bryan Korithoski, University Health Network, Toronto Canada; Khaled Kamal, Mount Sinai Hospital, Toronto Canada; Lori Burrows, University Health Network, Toronto Canada; Curtis Nickel, Queen Introduction and Objectives: The etiology of NIH type III (non-bacterial) prostatitis is undetermined. The concept that an undocumented bacterial infection may be contributing to this form of prostatitis is widely held. Culturing techniques to identify bacteria have been used for over 100 years, yet most microbial organisms remain difficult or impossible to culture. With the advent of molecular biology techniques to identify the bacterial genotype rather than the phenotype, it is now possible to detect any microorganisms, even those that are impossible to culture. We have applied the new molecular biology methods to determine the types of bacteria present in men with and without Type III prostatitis. Methods: Semen and urine (VB1, VB2 and VB3) samples from men with (23) and without (8) prostatitis were centrifuged, and then the pellet was washed twice with PCR buffer. The pellet was lysed with a Proteinase K based lysis buffer. PCR, using universal Eubacterial primers, was performed on an aliquot of the lysed pellet: the resulting amplicons were electrophoresed and UV fluorescence was used to identify amplicons of the correct length. The cleaned amplicons were then cloned and sequenced. These sequences were compared to bacterial sequences on deposit in the ribosomal database (Urbana, Illinois) using a BLAST search. Results: All semen and 47/58 urine specimens tested had bacterial DNA identified using universal Eubacterial PCR primers. A number of unusual organisms were identified in the urine and semen including Paenibacillus sp., Proteobacterium sp., Flavobacterium, uncultured eubacterium and Bradyrhizobium sp. The most frequently identified bacteria were of the Paenibacillus and Proteobacterium genera. These two genera were much more commonly found in men with prostatitis than in the controls. Conclusions: This is the first reported finding of Paenibacillus sp. or Proteobacterium sp. in the human genitourinary tract fluids. What is surprising is that these two previously undetected species are the most common bacteria found in men with prostatitis. In addition, there is a clear preponderance of these bacterial genera in the semen and urine of men with Type III prostatitis compared to asymptomatic controls. This suggests that these bacteria are associated with prostatitis: this association could be causative or it could be that the prostatic microenvironment in men with prostatitis is conducive to growth of these particular organisms. Antibiotic sensitivity could not be performed because those are unculturable bacteria.
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Detection of Borrelia burgdorferi in urine specimens from dogs by a nested polymerase chain reaction Zentralbl Bakteriol. 1998 May;287(4):347-61 Bauerfeind R, Kreis U, Weiss R, Wieler LH, Baljer G Institut fur Hygiene und Infektionskrankheiten der Tiere, Justus-Liebig-Universitat Giessen, Germany. A nested PCR (nested flagellin PCR) carrying an internal E. coli DNA control was established and compared with an in-vitro culture method for the detection of Borrelia burgdorferi in urine specimens of dogs. The predicted specific amplicon of the flagellin gene fla was generated from all cultured strains of B. burgdorferi tested (comprising three European genospecies). In contrast, all 13 strains of seven other flagellated bacterial species were negative. The PCR detection limit yielded 20 cells of B. burgdorferi per ml of double-distilled water and approx. 250 bacteria per ml of dog urine. Using the bacterial culture method, urine specimens collected from 216 dogs in Germany were all diagnosed negative for spirochetes by in-vitro culture and dark-field microscopy. In contrast, DNA of B. burgdorferi was detected in 32 specimens (14.8%) by PCR. 31 urine specimens (14.4%) showed inhibitory activity in the PCR assay. However, 94 (44%) were inhibitory in the culture assay. The majority of the PCR-positive dogs exhibited major clinical symptoms which have not been reported in the course of B. burgdorferi infection previously, e.g. cystitis (14/32 dogs) or prostatitis (5/32 dogs). Our results indicate that the analysis of urine specimens by the nested flagellin PCR is a highly valuable procedure for the diagnosis of B. burgdorferi infections in dogs.
Eur Urol. 2007 Apr;51(4):1119-27. Epub 2006 Nov 27 Chuang YC, et al. Department of Urology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan. OBJECTIVES: An animal model for nonbacterial prostatitis in rats was developed with the use of intraprostatic injection of capsaicin, an agent thought to excite C-afferent fibers and cause neurogenic inflammation. The analgesic and anti-inflammatory properties of botulinum toxin type A (BoNT-A) was tested in this model. METHODS: Adult male Spraque-Dawley rats were injected with varying doses of capsaicin into the prostate. The nociceptive effects of capsaicin were evaluated for 30min by using a behavior approach; then the prostate was removed for histology and cyclooxygenase (COX) 2 protein concentration measurement. Evans blue (50mg/kg) was also injected intravenously to assess for plasma protein extravasation. A second set of animals were injected with up to 20U of BoNT-A into the prostates 1 wk prior to intraprostatic injection of 1000mumol/l capsaicin. RESULTS: Capsaicin dose dependently induced modifications in pain behavior: closing of the eyes, hypolocomotion, and inflammatory changes: increase of inflammatory cell accumulation, COX2 expression, and plasma extravasation at the acute stage, but completely recovered at 1 wk. BoNT-A pretreatment dose dependently reversed pain behavior and inflammation. BoNT-A 20U significantly decreased inflammatory cell accumulation, COX2 expression, and Evans blue extraction (82.1%, 83.0%, and 50.4%, respectively), and reduced pain behavior (66.7% for eye score and 46.5% for locomotion score). CONCLUSIONS: Intraprostatic capsaicin injection induced neurogenic prostatitis and prostatic pain, and may be a useful research model. BoNT-A produced anti-inflammatory and analgesic effects, and support clinical evaluation in prostatitis.
European Urology 2000;38:393-399 (DOI: 10.1159/000020314). Dirk-Henrik Zermanna, Manabu Ishigookaa, Jörg Schubert, Richard A. Schmidta. Neurourology Unit, Department of Urology, University of Colorado Health Science Center, Denver, Colo., USA; Department of Urology, University Hospital, Friedrich Schiller University, Jena, Germany; and Department of Urology, Yamagata University Medical School, Yamagata, Japan. Background: Chronic prostatic pain is still a diagnostic and therapeutic problem. The clinical observation that prostatic and pelvic pain is accompanied by motoric and sensoric disorders of the pelvic floor muscles led to the hypothesis that prostatic pain roots in a changed processing of afferent and efferent information with the central nervous system (CNS). Methods: Neuro-urological work-up of 11 male patients with chronic prostatic pain was completed. This included a clinical evaluation of pelvic floor function, urodynamic investigation of bladder and urethra function and a cystoscopy to exclude morphological aberrations. A transurethral perisphincteric injection of 200 units botulinum toxin type A (BTX) was followed by a 2- to 4-week visit to evaluate their influence on the neuro-urological symptomatology. Results: All chronic prostatic pain patients suffered from a pathological pelvic floor tenderness, an inability of sufficient conscious pelvic floor control, a urethral hypersensitivity/hyperalgesia and a urethral muscle hyperactivity. Basic parameters of bladder function (capacity, sensitivity, compliance) were normal. The BTX injection was followed by a pelvic floor muscle weakening and a relief of prostatic pain and urethral hypersensitivity/hyperalgesia. A botulinum-related decrease of the functional urethral length, the urethral sphincter closure pressure, the postvoid residual volume and an increase of the peak and average uroflow were objectivated. Conclusion: A weakening of the urethral sphincter muscle via blocking acetylcholine release by BTX injection is followed by pain relief and symptom improvement. It can therefore be concluded that a barrage of nociceptive information from the dysfunctional pelvic floor overflood the CNS and induce a changed CNS processing. Interrupting the efferent branch of the disturbed central circle is one opportunity to treat chronic prostatic pain. Author
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Nicolai M, De Thomasis R, Di Federico G, Palmerio A, Iantorno R, Tenaglia R. Cattedra di Clinica Urologica, Universita degli Studi G. D'Annunzio, Chieti. Prostatitis syndromes are frequent and cause pain and discomfort in adult males. Non-bacterial types occur more often than bacterial prostatitis. Transrectal ultrasound permits a perfect evaluation of prostate, seminal vesicles and ejaculatory ducts. Fifty-five patients affected by prostatis syndrome and with negative bacteriological studies, underwent transrectal ultrasonography performed with 7.5 MHz probe. In 38 cases (70%) we found abnormalities such as subacute vesiculitis, asymmetric dilation of the seminal vesicle, dilated and calcific ejaculatory ducts, mullerian duct cyst, utricular cyst and calcification. Ultrasonography is able to detect these lesions that often are responsible of the clinical symptom of the prostatitis syndrome, and may have a therapeutic value through guided transperineal needle aspiration or in the planning specific endoscopic surgery. Publication Types: Clinical trial PMID: 9162337 [PubMed - indexed for MEDLINE]
Dellabella M., Milanese G., Muzzonigro G. Polytechnic University of the Marche Region, School of Medicine, Urology, Ancona, Italy INTRODUCTION & OBJECTIVES: Alterations of the bladder neck complex are frequently observed during transrectal ultrasound (TRUS) evaluation of patients affected by CP/CPPS. Such lesions are not well described in the literature. The aim of this prospective study was to evaluate the incidence of the bladder neck complex alterations and to correlate these lesions with other clinical parameters in young men affected by CP/CPPS. MATERIAL & METHODS: The bladder neck complex ultrasound alterations resulted in 15/25 (60%) consecutive CP/CPPS patients. We compared the ultrasound finding between 15 CP/CPPS patients and 15 healthy volunteers. All the men were < 50 years old; In each patient we evaluated both the IPSS score and NIH-CPSI score. The Qmax and the PVR were also recorded. The following ultrasound parameters were measured: prostate volume (PV), the hypoechoic periuretral zone volume (HPV), the posterior prostate lip thickness (LT), the bladder neck thickness (NT), the detrusor thickness (DT). Furthermore we evaluated the presence of prostate hyperechoic anterior stroma (AS) and of periuretral calcifications (PC). RESULTS: No differences were found in mean age and PV between the CP/CPPS group and the control group. In the CP/CPPS group resulted a significant reduction of the mean Qmax (14.5 vs. 26.0 ml/sec; p < 0.0001), a greater mean NIH-CPSI score (19.9 vs. 0.9; p < 0.0001) and a higher PVR (28.1 vs. 2.5 ml; p = 0.012) with respect to the control group. TRUS revealed significant differences among the two groups for all the evaluated parameters, but not for the PC frequency. There were close correlations between the NIH-CPSI score and HPV (rho = 0.798, p < 0.0001), and between NIH-CPSI score and LT (rho = 0.813; (p < 0.0001). CONCLUSIONS: The ultrasound evaluation of bladder-neck complex in this pathology could be useful for the possible role that such alterations could have on the pathogenesis of obstructive symptoms. The extimation of posterior lip and bladder neck could offer quantitative parameters to study the therapeutic effect of different drugs in CP/CPPS.
Eur Urol. 2004 Dec; 46 (6):760-4 BERKELEY, CA (UroToday Inc.) - Prostate cancer, benign prostatic hyperplasia and prostatitis are well established causes of elevated prostate specific antigen (PSA). Prostatitis, even if asymptomatic and chronic, particularly shows elevated serum PSA levels. According to the NIH (National Institutes of Health) classification, asymptomatic chronic prostatitis is defined by the presence of inflammatory cells in expressed prostatic secretion or histologically in prostate biopsy specimens and is classified as NIH category IV prostatitis. Free PSA is a promising tool for differentiating PCa (prostate cancer) from non-malignant conditions of the prostate. The effect of asymptomatic prostatic inflammation on total PSA (tPSA), free PSA (fPSA) levels and the f/tPSA ratio was examined to assess whether the role of free and percent free PSA can be used as a diagnostic tool to distinguish between cancer and non-malignant diseases of the prostate. The study was performed by I. Stancik and colleagues from Vienna, Austria, and published in the December, 2004 issue of European Urology. In a retrospective study, they evaluated data on 404 patients who underwent prostate biopsies and also had levels of serum free and total PSA available. All patients underwent 6 or 8 core prostate needle biopsies based on an elevated PSA of >4.0ng/ml or an abnormal DRE (digital rectal exam) or TRUS (trans-rectal ultrasound). Analysis showed that 100 patients were diagnosed with prostate cancer (24.8%), 143 patients (35.4%) had BPH, and 137 (33.9%) had NIH-IV prostatitis diagnosed on prostate biopsy. Twenty-four patients (5.9%) had both prostate cancer and NIH-IV prostatitis histologically and were excluded from the analysis. The mean levels of tPSA, fPSA and %fPSA were 11.94 ng/ml, 1.31 ng/ml and 15 (? felskrivning i någon av siffrorna) for NIH-IV prostatitis; 11.94 ng/ml, 1.54 ng/ml and 13 for prostate cancer; and 8.19 ng/ml, 1.48 ng/ml and 18 for BPH. No significant difference was found in tPSA levels between PCa and prostatitis (p= 0.32), while the difference in tPSA levels between PCa and BPH was significant (p= 0.0001). Free PSA alone was found to have no diagnostic power in distinguishing PCa from prostatitis and BPH. By contrast, the f/tPSA ratio showed significant between-group differences (PDA vs. prostatitis (p= 0.011), and PCa vs. BPH (p= 0.0001). The authors state that despite the statistical significance shown in this study, they cannot deduce if the fPSA/TPSA is a reliable discriminator between PCa and prostatitis for an individual patient. Based on their results, the authors recommend the use of the fPSA/tPSA ratio only as a diagnostic indicator and not as an absolute indicator to exclude biopsy in a patient for whom one would clinically recommend biopsy.
Prostatitis Syndromes. Ejaculate Changes and Effects on Fertility, Tyskland Urologe A 2001 Jan; 40(1):18-23. Ludwig M; Dimitrakov J; Diemer T; Huwe P; Weidner W. Urologische Klinik, Justus-Liebig-Universitat Giessen. Inflammation and infections of the male reproductive tract represent an important factor in male infertility that is potentially responsive to successful therapy (ja i vissa fall, ISOPs kommentar). A standardized diagnostic procedure is a prerequisite for the exact evaluation of alterations of ejaculate specimens, especially in cases of the different forms of the prostatitis syndrome. Several alterations in ejaculate due to inflammation and infection have been identified that have a negative impact on the quality of sperm. Besides the influence of leuko- and bacteriospermia, the effect of inflammatory mediators, such as cytokines and reactive oxygen species (ROS), are being discussed as relevant pathomechanisms. These parameters just recently were incorporated into the conventional range of diagnostic criteria. Clinical studies that investigate the quality of ejaculate in the different forms of the prostatitis syndrome yielded contradictory results. Only antimicrobial therapy has been sufficiently described as a therapeutic option. In the future, it will be decisive to include novel functional and molecular parameters to define an interaction of urogenital infection and male infertility.
Influence of urogenital infection on sperm function, USA & Tyskland CURRENT OPINION IN UROLOGY 2000;10:39-44 Thorsten Diemera; Martin Ludwig; Petra Huweb; Dale Buchanan Halesa; Wolfgang Weidnerb. Department of Physiology & Biophysics, University of Illinois at Chicago, Chicago, Illinois, USA, and Department of Urology, University Hospital, Justus-Liebig-University, Giessen, Germany. 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. Full text available free at: http://www.co-urology.com
World
J Urol. 2006 Jan 11;:1-6 Chronic pelvic pain syndrome/chronic prostatitis affect the acrosome reaction in human spermatozoa. There are a number of ways to check a man’s fertility. Traditionally, those have included sperm counts, sperm motility (the proportion of sperm that swim), and normal appearance. More recently, fertility experts have used the acrosome reaction to assess sperm quality. That reaction, in which the head of the sperm ruptures and releases enzymes, is the one that allows the sperm to penetrate the egg. Infection is known to have a negative effect on sperm quality and fertility, and inflammation is thought to have a negative effect. These German researchers looked at traditional measures of sperm quality and measurements of the acrosome reaction in normal men and men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), who often have evidence of inflammation (category IIIa, with white blood cells in the semen). and found that men with CP/CPPS appear to have significantly lower sperm quality, fewer acrosome reactions, and lower acrosome-reaction potential. The researchers compared these measurements between 95 control men and 56 men with CP/CPPS, including 24 with type IIIA and 32 with type IIIb. They found that men with both types of CP/CPPS had significantly lower sperm counts, lower proportions of normal sperm, and lower levels of acrosome reactions, and lower acrosome reaction potential.
Relationship between etiological factors and total motile sperm count in 350 infertile patients Arch Androl 1997 Nov-Dec;39(3):197-210 Martin-Du Pan RC; Bischof P; Campana A; Morabia A, Department of Obstetrics and Gynecology University of Geneva, Switzerland. The prevalence of different etiologic factors has been evaluated in 350 male patients consulting the same physician in an urban, ambulatory setting for primary or secondary infertility of more than 1 year. Environmental factors such as alcohol or drugs represented 12% of the etiologies, acquired diseases such as varicocele and prostatitis 40%, congenital diseases and primary testicular failure 16.2%, idiopathic cases 19.4%, and abnormality of sperm transport 7.4%. The severity of sperm alterations in the different etiologic categories was evaluated by the total motile sperm count per ejaculate (TMS) (normal > 16). The TMS was less than 5 in classical causes of male infertility such as testicular failure, endocrinopathy, cancer, or antisperm antibodies. It was more than 10 in controversial causes of infertility such as varicocele, prostatis, Chlamydial infections, and professional exposure to heat. After treatment, there was a nonsignificant increase of the TMS in the latter cases. In cases of azoospermia of pituitary origin, the TMS was normalized by a hormonal treatment. In some cases of azoospermia of possible obstructive origin, sperm appeared in the ejaculate after diclofenac treatment. The utility of andrological investigation and treatment is discussed. För mer information http://www.prostatitis.org/infertility2.html#prostatic%20cyst
Klinik und Poliklinik fur Urologie and Kinderurologie, Giessen, Germany Ludwig M, Johannes S, Bergmann M, Failing K, Schiefer HG, Weidner W. OBJECTIVE: To assess the effect of initial antimicrobial therapy with a new highly potent quinolone (Sparfloxacin) on the outcome of infection, especially acute and chronic inflammation, in a rat model of unilateral Escherichia coli epididymitis. MATERIALS AND METHODS: The study included 60 Sprague-Dawley rats, each of which received 0.1 mL of an E. coli (0:6 strain) suspension (106 colony forming units/mL) injected into the right ductus deferens. At 24 h after infection an oral antimicrobial treatment with sparfloxacin was initiated in half of the animals. The rats were killed 14 days, 3 and 6 months after infection, and both epididymes and the prostate gland cultured to re-isolate E. coli. To evaluate the grade of inflammation in both epididymes, histological variables, including acute and chronic inflammation and scar formation, were evaluated and a total inflammatory score, representing the sum of all variables, computed. RESULTS: Whereas antimicrobial therapy eradicated the pathogen, in untreated animals the pathogen was detectable for up to 6 months after infection in the infected epididymis and/or the prostate gland, while the contralateral epididymis was sterile. The inflammatory reaction in the infected epididymis was significantly less in treated animals (P < 0.001). Subclinical nonbacterial inflammation was present in the contralateral epididymis. CONCLUSIONS: Although adequate antimicrobial treatment eradicated the pathogen and reduced the grade of epididymal damage, inflammation was not avoided. Subclinical inflammation of the contralateral epididymis may contribute to impaired fertility. These results indicate that an inflammatory reaction initiated by bacteria might persist as a nonbacterial process despite early therapy, or by bacteria undetectable by conventional culture techniques, and may compromise male fertility.
Länk till sida om analys av sädesvätska m.m. Normal semen pH is 7.2-8.0. Prostatic secretion is acidic while seminal vesicle fluid is alkaline (seminal fructose is derived from seminal vesicles). Acidic ejaculate (pH<7.2) may be associated with blockage of seminal vesicles. Infection is usually associated with alkaline ejaculate (pH >8.0_ Azoospermia with low ejaculate volume, fructose negative and acidic may imply obstruction of the ejaculatory ducts. pH over 8.0 *may* indicate infection. The semen is initially in liquefied state but quickly coagulate by the action of protein kinase secreted by the seminal vesicles. Proteolytic enzymes from the prostate liquefy coagulum in 20-25 minutes. Abnormal liquefaction may be cased by prostatic abnormalities, e.g. prostatitis. Increased viscosity may affect sperm motility. Du kan läsa mer på följande URL: http://www.umc.sunysb.edu/urology/male_infertility/SEMEN_ANALYSIS.html
Comparison of microscopic methods for detecting inflammation in expressed prostatic secretions, USA. J Urol 2001 Dec;166(6):2518-24 Muller CH, Berger RE, Mohr LE, Krieger JN. Prostatitis Clinic and Male Fertility Laboratory, Department of Urology, University of Washington School of Medicine, Seattle, Washington. PURPOSE: We evaluated microscopic methods of detecting inflammation in expressed prostatic secretions. MATERIALS AND METHODS: Methods of counting expressed prostatic secretion leukocytes were compared in 251 samples from 159 patients with chronic prostatitis/chronic pelvic pain syndrome, including traditional wet mounts, hemocytometer derived concentrations and expressed prostatic secretion smears stained with Gram's method or DiffQuick stain (Dade International, Inc., Miami, Florida). RESULTS: Of 159 initial patient evaluations 84 (53%) showed inflammation by hem cytometer concentration at 500 leukocytes per mm.3 or greater but only 37 (23%) were considered inflammation by the traditional wet mount method (p <0.001). Inflammation was identified in 149 of 251 specimens (59%) by hemocytometer but in only 82 (33%) by wet mount (p <0.001). When inflammation was defined as 1,000 leukocytes per mm.3 or greater the hemocytometer still identified significantly more patients (41%) and specimens (48%) with inflammation than the wet mount. The hemocytometer method had a substantially lower interassay and intra-assay coefficient of variation than the wet mount method. Polymorphonuclear neutrophils and macrophages were the most common cells observed on stained smears, which detected inflammation in 147 specimens (59%) by DiffQuick but in only 98 (39%) by Gram's method. CONCLUSIONS: Detecting inflammation in expressed prostatic secretions is method dependent. Significantly more cases of inflammation were detected by hemocytometer than by the traditional wet mount technique. Because the wet mount method also proved more variable than the hemocytometer and highly sensitive to volume, its use is not recommended. These findings support the adoption of hemocytometer and staining methods for accurate evaluation of expressed prostatic secretion inflammation in men with chronic prostatitis/chronic pelvic pain syndrome. PMID: 11696821 [PubMed - in process]
John W. Polacheck, Tucson, AZ, L. Eduardo Vega. The Prostatitis Center and Carondelet St. Joseph's Hospital: Tucson, AZ. INTRODUCTION: We decided to compare semen and expressed prostatic secretions (EPS) from patients with chronic prostatitis using cytopathologic techniques in order to learn more about the pathophysiology of this disorder. METHODS: In patients with signs and symptoms of chronic prostatitis, we compared the cytopathology of their expressed prostatic secretions (EPS) obtained by prostatic massage to that of their semen obtained by ejaculation. Ten patients were studied (mean age 42 years, range 29-66). Semen was collected shortly after patients woke-up in the morning, and in each case they were instructed to void before collecting their sample. Immediately after obtaining the sample, 35 ml of preservative (50 percent isopropyl alcohol) was added, and the mixture was kept cool. Smears and cell blocks were prepared and staining was done with a modified Wright's, PAS, H&E and Papanicolau stains. For the EPS, two slides were made and stained with a modified Wright's stain and PAS. RESULTS: In 8 cases (80%), the EPS showed signs of acute inflammation, containing both individual polymorphonuclear leukocytes (PMNs) and cohesive aggregates of PMNs. We call these aggregates "PIAs", prostatic inflammatory aggregates. By sharp contrast, the semen from all the patients showed either no findings of inflammation (no PMNs nor PIAs) or only very mild changes (rare PMNs). In this small series, we did not observe PIAs in semen. COCLUSION: Our observations suggest that the muscular force of ejaculation is not sufficiently strong to express PIAs from the prostate, at least in the majority of patients with chronic prostatitis. PIAs can, however, be expressed by digital-rectal prostate massage. This provides objective evidence that digital-rectal massage of the prostate has a beneficial effect in patients with chronic Prostatitis. Furthermore, we see only scanty amounts of PAS positive protein in the total ejaculate specimens whereas it is prominent in EPS specimens. This suggests the total ejaculate of prostatitis patients contains only a minimal amount of prostate secretions. These observations have implications pertaining to fertility in patients with untreated chronic Prostatitis. Se även följande URL: http://www.medizin-forum.de/prostatitis/wbc-d.html och http://www.prostate-usa.com
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Diagnostic and therapeutic procedures for hemospermia H. John 1, 3 und M. Ludwig 2. (1) Urologische Klinik und Poliklinik, Universitätsspital Zürich, (2) Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Giessen, (3) Present Address: Urologische Klinik und Poliklinik, Universitätsspital, 8091 Zürich, Schweiz. Urologe [A] (2003) 42: 99-103, DOI: 10.1007/s00120-002-0271-6 Abstract: In general, hemospermia represents a trivial condition: nevertheless, it is often alarming for the patient and his partner. Although differential diagnosis is comprehensive, the most frequent underlying causes are infections and inflammatory processes in the lower seminal passages. Cases of primary and solitary hemospermia can be adequately assessed by urinalysis, blood pressure measurement, and reassurance of the patient. Persistent and recurrent cases of hemospermia are best clarified by transrectal ultrasound examination, cystoscopy, and magnetic resonance imaging. Treatment is based rationally on the examination results.
Journal of Clinical Microbiology Volume 34, Number 12. December 1996. Prokaryotic DNA Sequences in Patients with Chronic Idiopathic Prostatitis. John N. Krieger, Donald E. Riley, Marilyn C. Roberts, and Richard E. Berger 3120-3128. Half of all men experience symptoms of prostatitis at some time in their lives, but the etiology is unknown for more than 90% of patients. ”Optimal clinical and culture methods were used to select 135 men with chronic prostatitis refractory to multiple previous courses of antimicrobial therapy. The subjects had no evidence of structural or functional lower genitourinary tract abnor-malities, of bacteriuria or bacterial prostatitis by traditional clinical tests, or of urethritis or urethral pathogens by culture. Specific PCR assays detected Mycoplasma genitalium, Chlamydia trachomatis, or Trichomonas vaginalis in 10 patients (8%). Broad-spectrum PCR tests detected tetracycline resistance-encoding genes, tetM-tetO-tetS, in 25% of patients and 16S rRNA in 77% of subjects. The tetM-tetO-tetS-positive cases constituted a subset of the 16S rRNA-positive cases. Patients with 6S rRNA were more likely to have 1,000 (or more) leukocytes per cubic mm in their expressed prostatic secretions than men whose prostate biopsy specimens were negative for 16S rRNA (P less than 0.001). Based on direct sequencing and repetitive cloning, multiple sources of 16S rRNA were observed in individual patients. Sequences of 29 cloned PCR products revealed 16S rRNAs distinct from those of common skin and gut flora.” These findings suggest that the prostate can harbour microorganisms that are not detectable by traditional approaches.
Mycoplasma, chlamydia and ureaplasma Gabe Mirkin, M.D. WHAT THEY ARE: Mycoplasma, chlamydia and ureaplasma are the smallest of free-living organisms. They are unlike all other bacteria because they have no cell walls and therefore must live inside cells. They are unlike viruses because they can live in cultures outside of cells and can be killed by certain antibiotics. However, they cannot be killed by most antibiotics, as most antibiotics work by damaging a bacteria's cell wall. They can be killed by antibiotics such as the tetracyclines or erythromycins that do not act on a cell wall. WHAT DISEASES THEY CAUSE: If you feel sick and your doctor is unable to make a diagnosis because all laboratory tests and cultures fail to reveal a cause, you could be infected with any of these bacteria. The only way that you will be cured is for your doctor to suspect an infection with these germs and for you to take long-acting erythromycin or tetracyclines for several weeks, months or years. They are the most common cause of venereal diseases and are a common cause of muscle and joint pains, burning in the stomach, a chronic cough, and chronic fatigue. They can cause transverse myelitis (paralysis of the spine) (1); gall stones (2); a chronic sore throat (3); red itchy eyes, pain on looking at light and blindness (4); arthritis (5,19); brain and nerve damage with symptoms of lack of coordination, headaches and passing out; spotting between periods or uterine infections (6); kidney stones (7); testicular pain; asthma (8); heart attacks (9); strokes (10); cerebral palsy (11); premature birth (12); high blood pressure (13); nasal polyps (14); stuffy nose in newborns (15); chronic fatigue (16); belly pain (17); muscle pain (18); confusion, passing out and death (19); coughing, bloody diarrhea, and anal itching and bleeding. WHY THEY ARE SO DIFFICULT TO DIAGNOSE AND TREAT: Most doctors will not prescribe antibiotics to patients without a laboratory test that indicates a specific infection. No dependable test is available to rule in or out mycoplasma, chlamydia or ureaplasma infections. Most antibiotics will not kill these organisms and those that do have to be taken for many months and years. Furthermore, many infected people do not take medication long enough to be cured, or they may have a close contact with an infected person and become reinfected. Once these infections are allowed to persist for months or years, they are extraordinarily difficult to cure and often require treatment for many months. One venereal-disease patient in four takes medication as prescribed (20) and almost all women who still had chlamydia one month after treatment were reinfected by new or old partners (21). Usually your first symptoms from chlamydia, ureaplasma and mycoplasma are burning on urination, a feeling that you have to urinate all the time, terrible discomfort when the bladder is full and vaginal itching, odor or discharge. Other first symptoms include itchy eyes, a cough or a burning in your nose. You can be infected when an infected person coughs in your face, or you touch nasal or eye secretions from an infected person and put your finger in your nose or eye. Your chances for a cure are high if you are treated when you have only local symptoms; but after many months, the infection can spread to other parts of your body and make you sick or damage nerves, joints and muscles. If you feel sick and your doctor is unable to make a diagnosis because all laboratory tests and cultures fail to reveal a cause, you could be infected with mycoplasma, chlamydia or ureaplasma and can be cured only by taking long-acting erythromycin or tetracyclines for many months. HOW I TREAT: I often prescribe 500 mg of azithromycin twice a week and/or doxycycline 100 mg twice a day. You may require treatment for months or years, if your symptoms have gone on for many months or years: muscle and joint pains, a chronic cough, burning on urination, severe fatigue or signs of nerve damage. Many physicians disagree with these recommendations, so check with your doctor before you consider these treatments. For more information on some of the diseases and conditions that may be caused by these bacteria, see my reports on asthma, heart attacks, infertility, venereal disease, arthritis, and fibromyalgia. http://www.drmirkin.com/men/8307.html
Mycoplasma genitalium: Another important pathogen of nongonococcal urethritis, Japan THE JOURNAL OF UROLOGY March 2002;167:1210-1217 Takashi Deguchi, Shin-Ichi Maeda From the Departments of Urology, Gifu University School of Medicine, Gifu, and Toyota Memorial Hospital, Toyota, Japan. Purpose: We reviewed findings on the pathogenic role of Mycoplasma genitalium in nongonococcal urethritis and the treatment of men with M. genitalium positive nongonococcal urethritis. Materials and Methods: We reviewed literature selected from peer reviewed journals listed in MEDLINE and from resources cited in those articles from 1967 to January 2001. Results: M. genitalium was first isolated from 2 men with nongonococcal urethritis and thereafter it was shown to cause urethritis in subhuman primates inoculated intraurethrally. This mycoplasma has been detected significantly more often in patients with acute nongonococcal urethritis, particularly in those with nonchlamydial nongonococcal urethritis, than in those without urethritis. The prevalence of M. genitalium positive nonchlamydial nongonococcal urethritis is 18.4% to 45.5% of all nonchlamydial nongonococcal urethritis cases. In addition, the persistence of M. genitalium in the urethra after antimicrobial chemotherapy is associated with persistent or recurrent nongonococcal urethritis. M. genitalium is highly susceptible to tetracycline, macrolide and some new fluoroquinolones. The regimen of 100 mg. doxycycline orally twice daily for 7 days, which is recommended for chlamydial nongonococcal urethritis, seems to be effective for M. genitalium positive nongonococcal urethritis, although clinical data to substantiate this regimen are limited. Conclusions: The various results reported to date tend to support the proposition that M. genitalium is a pathogen of nongonococcal urethritis. However, currently diagnostic methods for this important mycoplasma are not available in clinical practice. Because of the possible association of the posttreatment presence of M. genitalium in the urethra with persistent or recurrent nongonococcal urethritis, eradication of this mycoplasma from the urethra is essential for managing M. genitalium positive disease. However, clinical data on treating M. genitalium positive nongonococcal urethritis are extremely limited. Thus, further studies are required to develop new diagnostic methods that would be available in clinical settings and establish a new treatment algorithm for nongonococcal urethritis, including M. genitalium positive disease.
Smallest Bacteria Found in Chronic Prostatitis Scand J Urol Nephrol. 2005;39(6):479-82. Mycoplasmas in semen of chronic prostatitis patients. Mycoplasmas, a type of bacteria, are some of the smallest free-living organisms. Various species are found in healthy people, especially in the mouth and genitourinary tract, but some have been associated with disease, including various urinary tract diseases and some immunodeficiency and autoimmune diseases. They are difficult to identify and culture, and a kit commonly used to detect them does not distinguish well among different species. These Estonian researchers looked for mycoplasmas in the semen of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and healthy controls. Using the kit first in 161 men, including healthy men and those with all categories of CP/CPPS (IIIa, the inflammatory type with white blood cells in semen and IIIb, the noninflammatory type, and IV, the inflammatory type with no symptoms). The kit detected mycoplasmas in all the groups of men, but a more precise method of identifying the bacterial species called polymerase chain reaction (PCR), used in 60 of these men, detected mycoplasmas more often in chronic prostatitis patients than healthy men. A quarter of the men with chronic prostatitis had mycoplasmas compared with about a fifth of the controls. In addition, the mycoplasmas occurred more frequently in the semen of men with category IIIa disease than in the healthy men. No healthy man had either Ureaplasma parvum or Mycoplasma gentialium, but some men in all categories of CP/CPPS had U parvum, and some men with IIIa disease had M genitalium. Although the numbers of patients in each group were very small, the differences between the CP/CPPS patients and controls for these two species were statistically significant. Further research has to be done to show whether these organisms may actually cause or trigger CP/CPPS.
The possible role of anaerobic bacteria in chronic prostatitis, Ungern Szoke I, Torok L,
Dosa E, Nagy E, Scultety S. Department of Clinical Microbiology, Albert
Szent-Gyorgyi Prostatis, the most common urological disease in men, afflicts between 25 and 50% of all adult men. Four clinical categories are recognized: acute and chronic bacterial prostatitis, non-bacterial prostatitis and prostatodynia. The role of Gram- positive aerobic bacteria and the different anaerobes in chronic bacterial prostatitis is still a matter of debate. During this study, the urethral discharge and the prostatic fluid obtained after prostatic massage of 50 patients with chronic prostatitis, confirmed by clinical examination and resistant to empirical quinolone therapy, were cultured under aerobic and anaerobic conditions. The parallel specimens from 24 patients exhibited high colony counts of Gram-positive and Gram-negative anaerobic bacteria, either alone (18 cases) or in combination with aerobic bacteria (6 cases). The specimens obtained after prostatic massage of the remaining 26 patients were completely negative for both aerobic (bakterier som behöver syre för att leva) and anaerobic (bakterier som inte kan leva i syre) bacteria. No Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum or Trichomonas vaginalis were isolated from these patients. Patients with chronic prostatitis who gave positive culture results for anaerobes were treated with amoxicillin/clavulanic acid (heter Spektramox i Sverige) or clindamycin (heter Dalacin i Sverige) for 3-6 weeks. After treatment, samples were again taken and cultured for all pathogens known to cause prostatitis. These post-therapeutic samples revealed a decrease or total elimination of the symptoms, and no anaerobic bacteria could be detected. ISOPs kommentar: Det skulle vara mycket intressant att se statsitik på hur många svenska laboratorier, som i samband med kronisk prostatit och interstitiell cystit, gör test på både aeroba och anaeroba bakterier?
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Fam Pract 2001 Jun;18(3):258-65 Related Articles, Books, LinkOut Santelmann H, Laerum E, Roennevig J, Fagertun HE. Department of General Practice and Community Medicine, University of Oslo, 0317 Oslo, Alpharma AS, 0212 Oslo and Parexel Medstat AS, 2001 Lillestroem, Norway. BACKGROUND: Antifungal therapy has been claimed to be effective in polysymptomatic patients with diffuse symptoms from multiple body systems and even well defined diseases, traditionally not related to fungi. Hypersensitivity to fungus proteins and mycotoxins has been proposed as the cause. METHODS: We conducted a 4-week randomized, double-blind, placebo-controlled study in 116 individuals selected by a 7-item questionnaire to determine whether the antifungal agent nystatin given orally was superior to placebo. At the onset of the study, the patients were free to select either their regular diet or a sugar- and yeast-free diet, which resulted in four different subgroups: nystatin + diet (ND); placebo + diet (PD); nystatin (N); and placebo (P). RESULTS: Nystatin was significantly better than placebo in reduction of the overall symptom score (P < 0.003). In six of the 45 individually recorded symptoms, the improvement was significant (P < 0.01). All three active treatment groups reduced their overall symptom scores significantly (P < 0.0001), while the placebo regimen had no effect (P = 0.83). The benefit of diet was significant within both the nystatin (ND > N) and the placebo groups (PD >P). CONCLUSIONS: Nystatin is superior to placebo in reducing localized and systemic symptoms in individuals with presumed fungus hypersensitivity as selected by a 7-item questionnaire. This superiority is probably enhanced even further by a sugar- and yeast-free diet. PMID: 11356731 [PubMed - in process]
Diagnosis and treatment of chronic abacterial prostatitis: A systematic review, USA. Ann Intern Med 2000 Sep McNaughton Collins M, MacDonald R, Wilt TJ General Medicine Unit, Massachusetts General Hospital, Boston 02114, USA. PURPOSE: The optimal management of chronic abacterial prostatitis is not known. A systematic review of the literature was done to answer the following questions: Are there accurate, reliable tests to diagnose chronic abacterial prostatitis? Are there effective therapies for it? DATA SOURCES: Studies were identified by searching MEDLINE (1966 to 1999), the Cochrane Library, and bibliographies of identified articles and reviews and by contacting an expert STUDY SELECTION: Diagnostic test articles were included if they reported on controlled studies; treatment articles were included if they reported on randomized or controlled trials. No language restrictions were applied. DATA EXTRACTION: For each selected article, two investigators independently extracted key data on study design, patient characteristics, diagnostic test or treatment characteristics, and outcomes. DATA SYNTHESIS: 19 diagnostic test articles and 14 treatment trials met the inclusion criteria The disparity among studies in design, interventions, and other factors precluded quantitative analysis or pooling of the findings. Diagnostic test articles included 1384 men (mean age, 33 to 67 years) and evaluated infection; inflammation, immunology, and biochemistry; psychological factors; and ultrasonography. Treatment trials included 570 men (mean age 38 to 45 years) and evaluated medications used to treat benign prostatic hyperplasia, anti-inflammatory drugs, antibiotics, thermotherapy, and miscellaneous medications. No trial was done in the United States. CONCLUSIONS: There is no gold-standard diagnostic test for chronic abacterial prostatitis, and the methodologic quality of available studies of diagnostic tests is low. The few treatment trials are methodologically weak and involved small samples. The routine use of antibiotics and alpha-blockers to treat chronic abacterial prostatitis is not supported by the existing evidence. PMID: 10979882, UI: 20417630
Treatment of experimental autoimmune prostatitis by BXL-628, a vitamine D receptor agonist Från http://www.icsoffice.org/ The International Continence Society Congress 2005, Montréal, Canada. Abstract 27 by Adorini L1, Amuchastegui S1, Aquilano F1, Cossetti C1, Mariani R1, Penna G11. Bioxell S.p.A., Italy Hypothesis/aims of study: Chronic non-bacterial prostatitis or chronic pelvic pain syndrome (CPPS, NIH category III) is a highly prevalent syndrome of suspected autoimmune origin, characterized by chronic pelvic pain with varying degrees of urogenital symptoms. Based on the marked inhibitory activity of the vitamin D receptor (VDR) agonist BXL-628 on basal and growth factor-induced proliferation of human prostate cells, and on its potent anti-inflammatory properties in different models, we have tested its capacity to treat experimental autoimmune prostatitis (EAP). Study design, materials and methods: EAP was induced in non obese diabetic (NOD) mice, a strain genetically prone to develop different autoimmune diseases, by injection of mouse prostate homogenate in complete Freund’s adjuvant (CFA). BXL-628 was administered orally 5 d/week at 100 ?g/Kg from day 14 to 28 post immunization. Results: Administration of BXL-628, at non hypercalcemic doses, for two weeks in already established EAP is able to inhibit significantly the intra-prostatic cell infiltrate, leading to a profound reduction in the number of infiltrating leukocytes, in particular CD4+ and CD8+ T cells, B cells, macrophages and dendritic cells. Immunohistological analysis demonstrates decreased cell proliferation, assessed by reduced expression of the proliferation marker Ki 67, and increased apoptosis, shown by increased staining revealed by the TUNEL assay, in prostates from BXL-628-treated mice. In addition, decreased production of the pro-inflammatory cytokines IFN-? and IL-17 is observed in T cells stimulated by TCR ligation of prostate-draining lymph nodes from BXL-628-treated NOD mice. Interpretation of results: The results indicate that BXL-628, at non hypercalcemic doses, is able to interfere with key pathogenic events in already established experimental autoimmune prostatitis. Concluding message: These data support the autoimmune pathogenesis of chronic non-bacterial prostatitis, and indicate that treatment with the VDR agonist BXL-628 may prove clinically beneficial in this syndrome.
Haarala M, Alanen A, Hietarinta M, Kiiholma P. Department of Obstetrics and Gynecology, University of Turku, Finland. Sjögren´s syndrome (SS) and systemic lupus erythematosus (SLE) are autoimmune disease which have many similarities with Interstitial Cystitis (IC), a urinary bladder disease with unknown etiology. This survey on occurrence, severity and nature of lower urinary tract symptoms among patients suffering from SS or SLE showed that these patients have significantly more urinary complaints, especially irritative bladder symptoms, than age- and sexmatched controls. In these groups 25%, 29% and 66%, respectively, were free of urinary symptoms. The prevalence's of mild symptoms were 61%, 62% and 27%, and severe symptoms in 14%, 9% and 7% in the respective groups. SS and SLE patients with urinary complaints reported mostly urinary frequency (27% and 62%) and suprapubic pain (36% and 34%) The most common symptom in the control group was stress urinary incontinence. The frequency of lower urinary tract problems in patients with SS and SLE supports the concept that autoimmune disorders also have bladder affections. PMID: 10805264. UI: 20263014
Neurogenic inflammation and chronic pelvic pain, USA World J Urol 2001 Jun;19(3):180-5 Wesselmann U. Department of Neurology, The Johns Hopkins University School of Medicine, Blaustein Pain Treatment Center, Baltimore, MD 21287, USA. pain@jhmi.edu Chronic pelvic pain is a puzzling disease entity. The pathophysiological mechanisms of chronic pelvic pain are not clear and current treatment strategies are often not successful, leaving patients as well as health care providers frustrated. In a subgroup of patients with chronic pelvic pain (e.g., interstitial cystitis, irritable bowel syndrome, vulvar vestibulitis, prostatodynia/prostatitis, and loin pain/hematuria syndrome) inflammatory changes are observed, for which no etiology has been identified. These inflammatory changes might be due to neurogenic inflammation. Applying the concept of neurogenic inflammation to chronic pelvic pain provides new insights into the pathophysiological mechanisms of these pain syndromes, makes it possible to account for the heterogeneity and variability observed in the clinical presentation, and might lead to the development of novel therapies.
Markku Leskinen, Olavi Lukkarinen and Timo Marttila. Division of Urology, Department of Surgery, University Central Hospital of Oulo, Oulo, Finland. From: Urology 53: 502-505 1999. Objectives: To investigate whether treatment of inflammatory chronic pelvic pain syndrome (ICPPS) with finasteride has any influence on symptoms associated with ICPPS. Methods: Forty-one patients with ICPPS were randomized (1:3) to treatment with either placebo (25%, n=10) or finasteride 5 mg daily (75%, n=31) for 12 months. Efficacy was evaluated by analysis of symptomatic improvement through response to symptoms questionnaires, pain evaluation on an analytic visual scale, analgesic use as reported in patient diaries, urine flow and residual volume and prostate volume. Results: Prostatitis Symptoms Severity Index and prostatism scores dropped significantly in patients in the finasteride group (P< 0.001 and P< 0.05, respectively) There were no statistically significant differences in pain between the groups. There were significant differences in the change of prostate volume and in serum prostate-specific antigen concentrations between the finasteride and placebo groups (P<0.03 and P< 0.02, respectively) The groups did not differ with regards to side effects. Conclusions: Our results indicate that finasteride has an effect in ICPPS. The mechanisms by which finasteride works in these patients are unclear and could not be solved in this pilot study, which had relatively few patients. A further trial with larger numbers is required to confirm these results.
Immunoligische Aspekte der chronischen Prostatitis, Tyskland R. U. Anderson aus: W. Vahlensieck, G. Rutishauser u.a., Benigne Prostatotpathien, Stuttgart, New York 1992, S. 52ff Über die Rolle der immunologischen Phänomene bei der chronischen Prostatitis, ob bakterieller oder abakterieller Ausprägung, wird seit vielen Jahren spekuliert. Die Produktion von Immunglobulinen im Serum und an der Mukosaoberfläche ist ein Maß für die Immunantwort des Menschen auf das Eindringen körperfremder Stoffe. Die Prostata kann als Sekretionsdrüse gesehen werden, in der sich Reaktionen auf spezifische Infektionen messen lassen. Reines Prostatasekret läßt sich durch Prostatamassage exprimieren, und die Immunglobuline (z.B. IgA und IgG) werden mittels hochentwickelter Mikroassayverfahren gemessen. In der Regel enthält das Prostataexprimat (EPS) von Männern jenseits des 50. Lebensjahres einen höheren Spiegel von IgA und IgG. Bei der chronischen bakteriellen Prostatitis könnte es sich um eine Folge eines eingeschränkten lokalen Immunschutzes der Schleimhautoberflächen handeln. In solchen Fällen wäre die Immuntherapie in Form einer Impfung günstig. Studien von Riedasch und Möhring (3), in denen eine aus verschiedenen inaktivierten Stämmen von Escherichia coli und anderen Enterobakterien bestehende Ganzzellvakzine zum Einsatz kam, zeigte keinen statistischen Unterschied bei der Reinfektionsrate von behandelten Probanden innerhalb der ersten zwei Monate. Dennoch kam es bei der Plazebo-Gruppe innerhalb von 6 Monaten zu höheren Reinfektionsraten, und bei einigen der behandelten Patienten, bei denen ein Reinfekt auftrat, war dies mit anderen Erregern als den ursprünglich festgestellten der Fall. Eine Pilotstudie über die Lymphozytentransformation wurde an 11 Probanden mit positiven humoralen Antikörpertitern durchgeführt. Bei dem mit entweder autologem Prostataexprimat oder homologem Prostataextrakt stimulierten Lymphozyten konnte kein signifikanter Anstieg der DNS-Synthese festgestellt werden. Diese Untersuchungen beweisen zwar nicht, daß es sich bei der abakteriellen Prostatitis um eine Autoimmunerkrankung handelt, sie lassen aber darauf schließen, daß bei einer großen Anzahl von Männern, die an diesem Syndrom leiden, Antikörper gegen ein Antigen des Prostatagewebes gebildet werden. Bei Langzeitstudien kam es zu Schwankungen der Titer der Prostata-Antikörper, die auch angesichts bleibend hoher Leukozytenzahlen im Prostatasekret auf nicht mehr feststellbare Mengen sanken. Es sind weitere Belege für die Spezifität des Antikörpers oder für die Tatsache, daß die Entzündung einen nicht spezifischen Autoantikörper hervorruft, erforderlich.
Eur Urol 2001 Jan;39 (1)72-78 John H, Barghorn A, Funke G, SulserT, Hailemariam S, Hauri D, Joller-Jemelka. HIClinic of Urology and Institutes of Clinical Pathology, Medical Microbiology, and Clinical Immunology, University Hospital, Zurich, Switzerland. OBJECTIVES: The aim of this prospective study was to observe immunophenotypic patterns in patients with noninflammatory chronic pelvic pain syndrome (Cat IIIB CPPS) for further description and as possible surrogate markers for diagnosis and treatment. METHODS: Eighty-eight patients with a referral diagnosis of chronic prostatitis underwent fractionated urinary cultures including expressed prostate secretion (EPS) and ejaculate analysis twice on two occasions. Monthly serum analyses included C3c, C4, IL-1alpha, sIL-2R, and IL-6. One hundred samples from healthy individuals were used as the control group for serum analysis. Monthly ejaculate testing was done for IgG, IgA, IgM, IL-1alpha, sIL-2R, and IL-6. The control group for ejaculate analysis was composed of 96 normal ejaculates (according to the WHO criteria). Immunohistochemical detection of CD3 cells (Tlymphocytes) and CD20 cells (B lymphocytes) was performed in 71 biopsy cylinders of Cat IIIB CPPS patients and in 25 prostate biopsy cylinders of men without symptoms or obstruction. RESULTS: Complete sampling of urinary, serum and ejaculate specimens was achieved in 50/88 (57%) patients. Cat IIIB CPPS was observed in 44/50 (88%) patients. Intra-acinar T-lymphocytic infiltrates were dominated by T cytotoxic cells (p = 0.05). Immunohistochemical studies showed inflammatory expression in serum complement, serum interleukin, and ejaculate interleukin concentrations in relation to the presence of large numbers of T cells (all p values </=0.01). No difference was found in the proportion of B lymphocytes in patients with Cat IIIB CPPS compared to the control group. Serum and ejaculate IL-6 and ejaculate IgA increased significantly and dropped again, correlating with a release of clinical symptoms. CONCLUSIONS: Interleukin, complement and immunoglobulin determinations in serum and ejaculate reveal an inflammatory process even in Cat IIIB CPPS. The findings of intra-acinar T-cell-rich infiltrates and the associated inflammatory reaction may be a significant advance in defining Cat IIIB CPPS caused by a possible autoimmune component. Serum and ejaculate IL-6 and ejaculate IgA are possible surrogate markers for the diagnosis and treatment of Cat IIIB CPPS
J Urol 2001 Nov;166(5):1738-41 Related Articles, Books, LinkOut Shahed AR, Shoskes DA. Harbor-University of California-Los Angeles Medical Center, Torrance, California, and Cleveland Clinic Florida, Fort Lauderdale, Florida. PURPOSE: The chronic pelvic pain syndrome is a clinically defined symptom complex of unclear etiology. We have noted increased oxidative stress in the prostatic fluid of these patients, implying an active inflammatory response. Immune cells can produce the natural opioid beta-endorphin at the site of injury, which may modulate pain. We measured beta-endorphin and the inflammatory marker prostaglandin E2 in the expressed prostatic secretions of men with prostatitis, and correlated the results with symptoms. MATERIALS AND METHODS: Expressed prostatic secretions samples from 70 patients and 8 asymptomatic controls were collected and frozen. beta-Endorphin and prostaglandin E2 were measured by enzyme-linked immunosorbent assay. Results were stratified according to prostatitis category and compared in individuals before and after therapy. RESULTS: In symptomatic patients beta-endorphin and prostaglandin E2 were not significantly different in categories II, IIIa and IIIb expressed prostatic secretions but they were higher than in controls. The mean beta-endorphin level plus or minus standard error of mean in symptomatic patients was significantly higher (23.8 +/- 11 ng./ml. versus 8.7 +/- 4.7, p = 0.0001) and mean prostaglandin E2 was lower (6.01 +/- 2.9 ng./ml. versus 3.01 +/- 2.9, p = 0.001) after successful therapy with antibiotics or antioxidant phytotherapy, Prosta-Q (Farr Laboratories, Santa Clarita, California). CONCLUSIONS: We observed a correlation of higher prostaglandin E2 and lower beta-endorphin in symptomatic men with chronic prostatitis. Increased oxidative stress and inflammation may induce prostaglandin E2 production that would inhibit beta-endorphin release. Treatment with therapeutic agents that decrease oxidative stress, such as antibiotics and antioxidant phytotherapy, may function at least partially by increasing beta-endorphin and decreasing prostaglandin E2.
Case builds for autoimmune component. Urology Times Nov, 1998 Chronic prostatitis: Case builds for autoimmune component. Author: Mac Overmyer Prostatic inflammation may exist even without the presence of bacteria, viruses, and leukocytes. Baltimore: A team of researchers here has uncovered evidence suggesting that some cases of chronic prostatitis/chronic pelvic pain syndrome may in fact be autoimmune disease, perhaps originating from earlier bacterial infection. Richard B. Alexander, MD, and colleagues from the University of Maryland and the Veterans Affairs Maryland Health Care System found elevated levels of tumor necrosis factor alpha (TNFa) and interleukin-1 beta (IL-1b) in the seminal fluids of men with the syndrome. "This suggests a continuing inflammatory process that can become active even in the absence of bacteria, viruses, or leukocytes," said Dr. Alexander, associate professor in the university's division of urology and chief of urology for the VA Maryland Health Care System. Last year, Dr. Alexander showed that T-cells from some men with the syndrome reacted to normal prostatic proteins, which also suggests a strong autoimmune component to the syndrome (Urology 1997; 50:893-9). Identifying the process underlying prostatitis in even a small percentage of patients would be welcome news. The condition accounts for an estimated 2 million office visits annually, but bacterial infection is identified as a causative entity in no more than 10% of cases. Empiric treatment with antimicrobial agents is a standard approach. These treatments can be long and expensive and carry the inherent risk of creating resistant organisms. Moreover, the benefits of such therapy have yet to be shown. The evidence of autoimmune disease is far from conclusive, but if it can be shown that some cases originate in the immune system, these men might benefit from investigational agents that reduce inflammation by blocking the actions of cytokines such as TNFa. Dr. Alexander's group identified 18 patients with a mean age of 38 who were diagnosed with chronic prostatitis/chronic pelvic pain syndrome. All patients presented with pelvic pain lasting longer than 3 months associated with voiding symptoms and sexual dysfunction, and all had been pretreated with antimicrobial therapies.Seminal fluid was obtained from the 18 patients as well as eight normal, healthy volunteers. The mean level of TNFa in the men with the syndrome was 98 pg/mL compared with 17 pg/mL in the normal volunteers (p=.039). The mean level of IL-1b was 246 pg/mL in the prostatitis patients and 27 pg/mL in the volunteers (p=.002). Don't count on leukocytes. The researchers noted that while the number of leukocytes per high-power field in expressed prostatic secretions (EPS) can provide evidence of prostatic duct inflammation, they found no correlation between leukocyte counts and cytokine levels. One intriguing observation was that no leukocytes could be found in the EPS of the patient with the highest cytokine levels. Conversely, some patients with higher than average leukocyte counts had cytokine levels comparable with those seen in the normal volunteers. These findings are "further evidence the number of leukocytes in EPS cannot reliably distinguish a meaningful sub-population of symptomatic patients with chronic prostatitis/chronic pelvic pain syndrome," the team reported. Dr. Alexander isn't surprised by the absence of a correlation with leukocytes. "These cytokines - seen in other inflammatory diseases such as rheumatoid arthritis and Crohn's disease - are secreted by monocytes," he told Urology Times. "The inflammation is in the tissue, not the ducts." Measuring cytokine levels in symptomatic men could be a means of objectively classifying disease severity and categorizing subgroups of patients for specific therapies, Dr. Alexander said. In turn, cytokine-inhibiting therapies may be a way of confirming whether or not some cases of prostatitis represent autoimmune disease. If the agents are proven to be clinically effective and if symptoms resolve when they are applied, the case for autoimmune disease would be more clearly established. Dr. Alexander's research was supported by grants from the National Institute of Diabetes, Digestive and Kidney Diseases and the U.S. Department of Veterans Affairs.
Mechanisms in prostatitis/chronic pelvic pain syndrome. J Urol. 2004 Sep;172(3):839-45. Pontari MA, Ruggieri MR. Department of Urology, Temple University School of Medicine, 3401 N. Broad Street, Philadelphia, PA 19140, USA. PURPOSE: We reviewed the current literature on mechanisms involved in the pathogenesis of prostatitis/chronic pelvic pain syndrome (CPPS). MATERIALS AND METHODS: A literature review for the years 1966 to 2003 was performed using the MEDLINE database of the United States National Library of Medicine. RESULTS: National Institutes of Health categories I and II prostatitis result from identifiable prostatic infections, whereas patients with category IV are asymptomatic. The majority of symptomatic cases are category III or chronic prostatitis (CP)/CPPS. The etiology of CP/CPPS is unknown. The traditional marker of inflammation, namely white blood cells in prostatic fluids, does not correlate with the predominant symptom of pelvic pain. An imbalance toward increased proinflammatory and decreased anti-inflammatory cytokines has been implicated and a few studies have shown some correlation of this with pelvic pain. The imbalance in some men may result from polymorphisms at the cytokine loci. An autoimmune process may be involved and experimental evidence indicates that this can be under hormonal influence. Recent findings include possible defects in the androgen receptor. The prostate may not even be the source of the symptoms. Pelvic pain also correlates with the neurotrophin nerve growth factor implicated in neurogenic inflammation and central sensitization. Finally, psychological stress may produce measurable biochemical changes and influence the other processes. The role of normal prostatic bacterial flora in inciting the inflammatory response has also been reconsidered. CONCLUSIONS: The symptoms of CP/CPPS appear to result from an interplay between psychological factors and dysfunction in the immune, neurological and endocrine systems.
Cho IR, Keener TS, Nghiem HV, Winter T, Krieger JN. Department of Urology, University of Washington School of Medicine, Seattle, USA. PURPOSE: We determine whether the chronic prostatitis/pelvic pain syndrome is associated with abnormal prostate blood flow. MATERIALS AND METHODS: We used color Doppler ultrasonography to examine 53 patients with inflammation, 80 men without inflammation and 22 healthy controls. Images were recorded and scored using standardized criteria to characterize the degree and distribution of prostatic vascularity. RESULTS: Flow was observed to the entire prostatic capsule in 77% of patients but only 18% of controls (p<0.0001). Parenchymal flow was evaluated using several criteria. On a 2-point scale flow was classified as grade 2 in 74% of patients compared to 27% of controls (p<0.0001). Similar findings were noted on a Doppler spot scale, with flow classified as grade 2 in 47% of patients compared to 14% of controls (p<0.004). Patients also had more parenchymal Doppler spots than controls (p<0.01). Diffuse blood flow throughout the prostatic parenchyma was observed in 63% of patients compared to 36% of controls (p<0.03). There was no significant difference in the amount or distribution of blood flow in patients with and without inflammation. CONCLUSIONS: The chronic prostatitis/pelvic pain syndrome was associated with increased blood flow to the prostatic capsule and diffuse flow throughout the prostatic parenchyma. Despite technical limitations, color Doppler ultrasonography may provide objective documentation of prostate blood flow abnormalities in patients with this syndrome.
J Urol 2002 Jan;167(1):137-140 Mehik A, Hellstrom P, Nickel JC, Kilponen A, Leskinen M, Sarpola A, Lukkarinen O. Division of Urology, Departments of Surgery and Public Health Science and General Practice, Oulu University Hospital, Oulu and Division of Urology, Department of Surgery, Seinajoki Central Hospital, Seinajoki, Finland, and Department of Urology, Queen's University, Kingston, Ontario, Canada. PURPOSE: We performed a prospective study to confirm early results implying that intraprostatic tissue pressure is elevated in men with the chronic prostatitis-chronic pelvic pain syndrome. We planned to determine further whether this technique would detect a significant difference in inflammatory and noninflammatory categories IIIA and IIIB. MATERIALS AND METHODS: A total of 48 patients with the chronic prostatitis-chronic pelvic pain syndrome, including 18 with inflammatory category IIIA and 30 with noninflammatory category IIIB disease, and 12 asymptomatic controls completed a Finnish version of the National Institutes of Health-Chronic Prostatitis Symptom Index. In addition, culture and microscopy of lower urinary tract segmented specimens, serum prostate specific antigen determination, transrectal ultrasound, uroflowmetry and ultrasound post-void residual urine measurement were done. All patients and controls also underwent independent intraprostatic right and left lobe tissue pressure measurement using a standard intracompartmental tissue pressure monitor system. Pressure was measured via an intraprostatic needle placed percutaneously in the perineum at baseline, and 10, 60 and 120 seconds after standard saline injection. RESULTS: All patients with the chronic prostatitis-chronic pelvic pain syndrome had significantly higher pressure at all measurement points compared with controls (p <0.001). Mean intraprostatic tissue pressure was significantly higher (p <0.01) in category IIIA with greater than 10 leukocytes per high power field in prostate specific specimens compared with category IIIB with less than 10. CONCLUSIONS: Our study supports the suggestion that patients with the chronic prostatitis-chronic pelvic pain syndrome have significantly higher prostate tissue pressure than controls. Findings also validated the previous clinical assumption that there is a rationale for differentiating chronic prostatitis-chronic pelvic pain syndrome cases into inflammatory and noninflammatory categories. PMID: 11743292 [PubMed - as supplied by publisher]
J Urol 2002 Feb;167(2 Pt 1):753-6 Miller LJ, Fischer KA, Goralnick SJ, Litt M, Burleson JA, Albertsen P, Kreutzer DL. Department of Pathology, University of Connecticut, School of Medicine, Farmington, Connecticut, USA. PURPOSE: Chronic prostatitis-chronic pelvic pain syndrome is a disease of unknown pathogenesis. We investigated whether the chronic inflammation and pain experienced by patients may be caused by an imbalance of proinflammatory versus anti-inflammatory cytokines within the prostate, namely interleukin (IL)-8, interferon-gamma and IL-2 versus IL-10. We measured these inflammatory cytokines in seminal plasma as a reflection of the prostate environment. MATERIALS AND METHODS: We measured levels of IL-8, interferon-gamma, IL-2 and IL-10 in the seminal plasma of 31 patients with chronic prostatitis-chronic pelvic pain syndrome and 14 controls using enzyme-linked immunosorbent assay. Results were correlated with health related quality of life, as measured by the Multidimensional Pain Inventory, McGill pain questionnaire and International Prostate Symptom Score. RESULTS: The cytokines analyzed were detectable in the seminal plasma of patients with chronic prostatitis-chronic pelvic pain syndrome and controls. Interferon-gamma, IL-2 and IL-10 levels were statistically greater in patients. Furthermore, IL-10 levels correlated directly with measures of life interference (r = 0.52, p <0.01) and pain severity (r = 0.53, p <0 0.01), and inversely with spousal support (r = -0.39, p <0.04). CONCLUSIONS: Our study suggests that IL-10 may have a role in the pain symptoms experienced by patients with chronic prostatitis-chronic pelvic pain syndrome. PMID: 11792966 [PubMed - in process]
Protein Search Yields Potential Markers, Treatment Target From AUA meeting 2007. A panel of potential diagnostic biomarkers for chronic prostatitis/chronic pelvic pain syndrome. Jordan D Dimitrakov, Boston, MA; Jayoung Kim, Jaeseop Lee, John Quackenbush, Boston, MA; Weidong Zhou, Lance Liotta, Emanuel Petricoin, 111, Manassas, VA; David Zurakowski, Michael R Freeman, Boston, MA; J. Curtis Nickel, Kingston, ON, Canada. Proteomics is a fairly new approach to investigating disease using a large-scale protein identification. By identifying the differences in the particular proteins that people with a disease produce compared with healthy people, researchers can home in on disease markers, the causes of disease, and even treatments. Applying proteomics techniques to pre- and postprostatic massage urine of CP/CPPS patients and controls, these investigators identified 133 unique proteins in the postmassage urine of men with CP/CPPS. The top six protein candidates were PSA, zinc alpha 2 glycoprotein (ZA2G), neprilysin (NEP), aminopeptidase N (APN), decapentaplegic protein (DPP), and Tamm-Horsfall protein (THP). One of these may prove to be a useful biomarker. NEP is especially interesting because it is a protein that neutralizes enkephalin, one of the body's natural painkillers. This may be a basis of the pain in chronic prostatitis and also points to potential treatment.
Nerve growth factor and chronic prostatitis/chronic pelvic pain syndrome Urology 2002 Apr;59(4):603-8 Related Articles, Books, LinkOut Miller LJ, Fischer KA, Goralnick SJ, Litt M, Burleson JA, Albertsen P, Kreutzer DL. Department of Pathology, University of Connecticut School of Medicine and School of Dental Medicine, Farmington, Connecticut 06030, USA. OBJECTIVES: To investigate whether the pain experienced by patients with chronic prostatitis/chronic pelvic pain syndrome (CPPS) may be related to the expression of nerve growth factor (NGF), induced by inflammation and tissue injury experienced as a result of chronic inflammation. CPPS is a disease of unknown pathogenesis. METHODS: We measured the levels of NGF and the pro-inflammatory cytokine interleukin (IL)-6 and compared these with the levels of IL-8, interferon-gamma, IL-2, and IL-10 in the seminal plasma of 31 patients with CPPS and 14 controls using enzyme-linked immunosorbent assay technology. Results were correlated with health-related quality of life as measured by the multidimensional pain inventory, the McGill pain questionnaire, and the International Prostate Symptom Score. RESULTS: The cytokines analyzed were detectable in the seminal plasma from the patients with CPPS and controls. NGF correlated directly with pain severity (P <0.01) and IL-10 levels (P <0.04), and IL-6 correlated inversely with pain severity (P <0.03). CONCLUSIONS: These results suggest that NGF and cytokines that regulate inflammation (IL-6 and IL-10) may play a role in the pain symptoms experienced by patients with CPPS. PMID: 11927336 [PubMed - indexed for MEDLINE]
MIP-1 AND MCP-1: NOVEL BIOMARKERS FOR CHRONIC PROSTATITIS Jeffrey A. Stem, Chicago, IL; Alisa E. Koch, Phillip L. Campbell, Ann Arbor, MI; J. Richard, Landis, Philadelphia, PA; Anthony J. Schaeffer, Chicago, IL Two cytokines could become useful biomarkers for diagnosing CPPS. These researchers found that levels of the two cytokines in expressed prostatic secretions from men with CPPS distinguish them from healthy men. Known as macrophage inflammatory protein-1 (MIP-1) and monocyte chemoattractant protein-1 (MCP-1), these cytokines may also play a role in the actual disease process. MIP-1 attracts the types of white blood cells known as a macrophages and T lymphocytes, and MCP-1 attracts mononuclear phagocytes. The researchers looked for these two cytokines in specimens from 12 healthy men, 25 men with category IIIA prostatitis or inflammatory CPPS (who show white blood cells in the specimens), and 28 men with type IIIB prostatitis or noninflammatory CPPS. The mean levels of MIP-1 in those groups were 148.88 pg/mL, 1162.85 pg/mL, and 1384.05 pg/mL, respectively, and the mean levels of MCP-1 were 599.43 pg/mL, 3302.21 pg/mL, and 1927.88 pg/mL, respectively. The levels in both CPPS groups were significantly higher than in the healthy men. Using a cutoff point of 69.99 pg/mL for MIP-1 and a cutoff point of 1061.84 for MCP-1 yielded a sensitivity of 88.7 % and specificity of 80 % for detecting CPPS.
Short tandem repeat sequences in chronic prostatitis/chronic pelvic pain syndrome, USA John N Krieger*, Donald E Riley, University of Washington & VA Puget Sound Health Care System, Seattle, WA. Introduction and Objectives: Genetic variations in the region of the X-chromosome are important in urological disorders such as prostate cancer (CaP) and androgen insensitivity. In women, the risk of recurrent urinary tract infection reflects genetic background, e.g., blood group antigen and secretor status. Our objective was to assay the polymorphic, phosphoglycerate kinase (PGK1) gene short tandem repeats (STRs) in a region implicated in familial CaP, androgen insensitivity, and hypospadias to determine if potentially predisposing genetic differences exist in chronic prostatitis (CP/CPPS) patients. Methods: We used fluorescent PCR analysis and DNA sequencing to measure polymorphic PGK1 STR alleles. PGK1 STR allele sizes were measured in 180 CP/CPPS patients and 299 control subjects. Results: Nine alleles were detected in the 479 individuals studied. Alleles consisted of between 8 and 15 repeats of the tetrameric STR core sequence based on DNA sequencing. Alleles were named for the number of STR repeats they contained. The frequencies of the 9.5, 10 and 12 alleles in the CP/CPPS patients differed from the controls (p = 0.02). Conclusions: These results suggest that genetic predisposition associated with the PGK1 gene, or another gene within Xq11-Xq13, such as the androgen receptor gene should be investigated further. This approach may provide important insights into the pathogenesis of CP/CPPS and open this field to powerful new genetic techniques. Ultimately, it may prove possible to use such genetic information to predict a patient's ability to resolve CP/CPPS or his response to possible therapeutic interventions
Discussion, J Urol 2001 May (Prof. J. Nickel study highlights), Kanada J Urol 2001 May;165(5):1539-1544 (Prof. J Curtis Nickel, Canada. Study Highlights) Patients clinically diagnosed with the chronic prostatitis/chronic pelvic pain syndrome have an approximate 45% to 65% chance of significant symptom amelioration after a 12-week course of ofloxacin therapy. The prevalence of uropathogenic bacteria, significant leukocytosis and/or increased uropathogenic bacterial antibody levels in prostate specific specimens didnot predict the ultimate outcome. These findings have significant ramifications for clinical practice and suggest important avenues for research studies. Traditionally, experts in the field of prostatitis have recommended that antibiotics should only be used for culture proved bacterial prostatitis.13-15. However, multiple clinical practice surveys confirm that many urologists prescribe antibiotics for the majority of their patients with prostatitis regardless of cultures or microscopic findings, if they were done at all.2-4. The outcome measured in most published randomized controlled studies evaluating antibiotic therapy for chronic prostatitis is the successful eradication (usually short term) of uropathogenic bacteria rather than amelioration of symptoms.5 It has been suggested that future studies evaluating the role of antibiotics for treating the chronic prostatitis/chronic pelvic pain syndrome must address the long-term effect of therapy on symptoms.7,16,17. Uncontrolled clinical studies have generally indicated that approximately 40% of patients with chronic prostatitis have some symptomatic improvement with antibiotic therapy1,18-22. Unfortunately and to our knowledge, antibiotics have never been compared with placebo in patients with the chronic prostatitis/chronic pelvic pain syndrome. A European consensus report showed that antibiotic therapy is indicated for category II chronic bacterial prostatitis and suggests that a trial of antibiotic therapy for the category IIIA inflammatory chronic pelvic pain syndrome is justified but not for the category IIIB noninflammatory chronic pelvic pain syndrome.21 The rationale for these suggestions, which are generally accepted by the urological community, is based on the theory that there is a definite bacterial etiology for category II and a possible one for category IIIA. However, in our study there was no significant difference in the degree of symptom amelioration or the number of patients who noticed improvement with antibiotic therapy when they were stratified as category II, IIIA or IIIB before therapy. Wishnow and Stamey found that control patients (10) and men with chronic abacterial prostatitis (4) had no antibodies to gram-negative bacterialantigens in contrast to those with bacterial prostatitis (6). 23 They hypothesized that immunological analysis may provide a better diagnostic tool than culture and microscopy. Shortliffe et al found that total IgA and IgG in the prostatic fluid of men with chronic abacterial prostatitis were higher than in controls.8,9,24,25 They also discovered that prostatic fluid from control or abacterial prostatitis cases did not contain specific antibodies to gram-negative urinary pathogens in contrast to those with bacterial prostatitis. In our study there appeared to be no significant difference in improvement in patients with increased antibody activity against potential bacterial uropathogens in the urine after prostatic massage compared to those with no significant antibody presence. There are 3 possible explanations as to why antibiotics improve symptoms in all categories of prostatitis. Antibiotics may have a powerful placebo effect. The few contemporary placebo controlled trials on chronic prostatitis show that placebo improvement in the chronic prostatitis syndrome ranges from 10% to 20%.10,26 However, placebo response in many other studies of urology have been reported to be as high as that obtained in our study, and a significant and profound placebo effect cannot be discounted. Prolonged antibiotic therapy may eradicate offending microorganisms that are believed to benonpathogenic, or not routinely cultured or able to be cultured with traditional techniques. Candidates include Chlamydia, Mycoplasma, coagulase negative Staphylococci, diphtheroids, Corynebacterium or bacterial aggregates protected in intraductal biofilms.27 The antibiotic may have a beneficial effect other than killing bacterial pathogens. Prostatitis is associated with increased cytokine, reflecting an ongoing immunological and/or inflammatory process.28,29 Antibiotics, especially the fluoroquinolones, have been shown to influence cytokine activity. Ciprofloxacin modulates interleukin-6 and interleukin-8 expression,30 while levofloxacin also has an immunomodulatory action on cytokine production independent of antimicrobial activity.31 Cotrimoxazole has been prescribed for the immunosuppressive or anti-inflammatory effects on noninfectious disease.32 Antibiotics decrease detectable cytokine in expressed prostatic secretions of patients with chronic prostatitis,33 and they also appear to have a relative analgesic effect, at least in animals.34 Because all patients included in our study complained of pain and/or discomfort, it is possible that we may have measured an anti-inflammatory and/or analgesic effect rather than antimicrobial action. It seems reasonable to suggest that patients diagnosed with the chronic prostatitis/chronic pelvic pain syndrome be subjected to a least 1 trial of antibiotic therapy, regardless of culture or microscopic evaluation of the lower urinary tract. Our study would indicate that if patients did not respond to a 4-week course of an antibiotic, further antibiotic treatment may not be helpful. It is surprising that antibiotic therapy, to our knowledge the most popular choice of all physicians for treatment of chronic prostatitis, has never been rigorously evaluated. Our study confirms that a randomized controlled study comparing antibiotic to placebo therapy is urgently required before we can practice evidence based medicine for treatment of the chronic prostatitis syndrome. REFERENCES 1. Weidner, W., Schiefer, H. G., Krauss, H. et al: M. Chronic prostatitis: a thorough search for etiologically involved microorganisms in 1461 patients. Infection, 19: 119,1991 2. Moon, T. 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The Female Prostate, Prostatitis, and Recurrent Urinary Tract Infection, Slovakien. M Zaviacic,1 RJ Ablin2 1Institute of Pathology, Comenius UniversitySchool of Medicine, Bratislava, Slovakia (MZJ,2Innapharma, Inc., Suffern, NY (RM). In contrast to the almost 2 million office visits annually in the United States for male prostatitis, in excess of 5 million office visits by women have been noted for the urethral syndrome, the commonest urologic complaint among female patients, attributed to infection in the distal paraurethral glands ("the female prostate"). Given the general misconception that the prostate gland is exclusively a male organ, the failure to recognize the existence of the female prostate and to investigate its pathology have resulted in the misdiagnosis and inappropriate treatment of female prostatitis. In consonance with earlier anatomical and embryological data, our extensive anatomical, light and electron microscopic, biochemical, and immunohistochemical studies of the normal and pathologic adult human female prostate substantiate the unambiguous existence of the female prostate. The female homologue of the male prostate is susceptible to the same diseases, including prostatitis. Within this framework, it appears rational, in the interim of further studies, to apply knowledge gained from immunobiological studies of the male prostate suggesting the existence of what has been termed the "prostatolymphoreticular system," to the female prostate. If the female prostate exhibits the similar immunopermissiveness of its male counterpart, it may also serve as a nidus for various infectious agents, inclusive of HIV. Of particular significance in this regard, as elucidated from our studies, are the substantially increased number of mutually communicating ducts and intraepithelial glands with the urethra and anterior wall of the vagina in the female vs. male prostate. Providing an environment exceptionally favourable for the long-term survival of uropathogens, it is suggested that this may not only explain relapses of female prostatitis, but also the recurrent episodes of urinary tract infections diagnosed as acute cystitis. Richard J. Ablin, PhD, Director, Scientific Investigation, Innapharma, Inc., Suffern, NY 10901, Tel: (914) 357-4100, Fax: (914) 369-7899
Histol Histopathol 2000 Jan;15(1):131-42 Zaviacic M, Ablin RJ. Department of Pathology, Comenius University School of Medicine, Bratislava, Slovakia. Prostate-specific antigen (PSA) is currently the most frequently used marker for the identification of normal and pathologically altered prostatic tissue in the male and female. Immunohistochemically PSA is expressed in the highly specialized apically-superficial layer of female and male secretory cells of the prostate gland, and as well as in uroepithelial cells at other sites of the urogenital tract of both sexes. Unique active moieties of cells of the female and the male prostate gland and in other parts of the urogenital tract are indicative of secretory and protective function of specialized prostatic and uroepithelial cells with strong immunological properties given by the presence of PSA. In clinical practice, PSA is a valuable marker for the diagnosis and monitoring of diseases of the male and the female prostate, especially carcinoma. In the female, similarly as in the male, the prostate (Skene's gland) is the principal source of PSA. The value of PSA in women increases in the pathological female prostate, e.g., carcinoma. Nevertheless, the total amount of PSA in the female is the sum of normal or pathological female prostate and non-prostatic female tissues production, e.g., of diseased female breast tissue. The expression of an antigen specific for the male prostate, i.e., PSA in female Skene's glands and ducts, and structural and functional parameters and diseases similar to that of the male prostate, have provided convincing evidence of the existence of a prostate in women and definitive preference of the term "prostate" over that of Skene's glands and ducts. The use of the term Skene's glands incorrectly implies that some other structure rather than prostate is involved, promoting the vestigial position of this female organ. Publication Types: Review Review, tutorial PMID: 10668204 [PubMed - indexed for MEDLINE]
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