Svensk forskning (prostatit/uretrit/IC)

 

—  svensk forskning är begränsad inom det här området 

 

 

Då jag hittar artiklar som rör svensk forskning kring kronisk prostatit och närliggande områden, kommer detta att läggas in på den här sidan. Jag är tacksam för alla tips.

 

I Storbritannien finns en organisation som heter Prostate UK. I deras informationsmateriel (från maj 2006) kan man bl.a. läsa följande: "Until recently little scientific effort had been focused on the prostate. Prostate cancer, BPH and prostatitis were all Cinderella disorders, losing out to more high profile medical conditions both in terms of medical interest and research funding. Prostate Research Campaign UK, founded in 1994, has worked hard to overcome this neglect by raising money to fund relevant research, increasing public awareness and providing information on ALL prostate diseases."

 

 

  Forskning rörande kronisk abakteriell prostatit, Skövde Observera!

  Prof. Hans Hedelins forskningsresultat

  Chronic abacterial prostatitis: Living with a troublesome disease affecting many aspects of life

  Increased expression of CCAAT/enhancer-binding protein beta in proliferative inflammatory atrophy of
      the prostate: relation with the expression of COX-2, the androgen receptor, and presence of focal chronic
      inflammation

  Interstitiell cystit, molekylärbiologiska studier

  The use of intraprostatic nitric oxide measurements to differentiate between inflammatory and
      non-inflammatory abacterial chronic prostatitis

  Dr. H. Wedren 

  Dr. B. E. Persson m.fl.

  Dr. L. Carlsson m.fl.

  Symptomatic urethritis is more prevalent in men infected with Mycoplasma genitalium than with
      Chlamydia trachomatis

  Ameliorative effect of allopurinol on nonbacterial prostatitis: a parallel double-blind controlled study

  Pain in and health-related quality of life in a geographically defined population of men with prostate cancer

  In Vitro Pharmacodynamics of the New Ketolides HMR 3004 and HMR 3647 (Telithromycin) against
      Chlamydia pneumoniae

  Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue:
      Sildenafil and papaverin generate inhibition

 

 

Forskning rörande kronisk abakteriell prostatit (oss veterligt den enda officiella i Sverige) pågår f.n. (i början 2006) med ett begränsat antal patienter vid Kärnsjukhuset i Skövde under ledning av Prof. Hans Hedelin.

Under rubriken Sammanfattning.

Kronisk abakteriell prostatit (k.a.p.) är ett symtomkomplex med en duration på minst 3 månader karakteriserat av:

1. Smärtor lokaliserade suprapubiskt, till perineum, ländrygg och yttre genitalia.

2. Vattenkastningsbesvär i form av täta imperativa urinträngningar, ofta sveda vid vattenkastningen (men utan bakteriuri) och stråle av varierande styrka.

3. Sexuell dysfunktion med bl a nedsatt lust, smärtsamma ejakulationer.

K.a.p. drabbar var 10:e man med ofta mycket långdragna besvär. Orsaken är okänd, kausal behandling saknas och även den symtomatiska behandlingen är otillfredsställande.

Diagnosen ställs på anamnesen (och avsaknad av bakteriuri) distinkta objektiva kriterier för diagnosen saknas. Kunskap om hur de olika delsymtomen påverkar den drabbade mannen och hur de samvarierar och påverkas av utlösande faktorer som t ex kyla saknas vilket kan synas märkligt då det är ett så vanligt tillstånd. Den kliniska erfarenheten antyder vidare att det finns flera orsaker bakom k.a.p. där var och en ger sitt "symtommönster".

Tanken med den nu planerade studien är att via intervjuer av män med k.a.p. i olika svårighetsgrad och duration öka kunskapen om de k.a.p. associerade symtomen och försöka utveckla kriterier för när diagnosen kan ställas (då på förhoppningsvis mer objektiva grunder). Avsikten är också att försöka klarlägga och definiera de olika former av k.a.p. som sannolikt finns, något som inte tidigare studerats.

 

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Scand J Urology Nephrology 2008 July 10:1-6

Chronic Abacterial Prostatitis: Living With a Troublesome Disease Affecting Many Aspects of Life - Abstrac.

Written by Jonsson K, Hedelin H.

Chronic abacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a disease of yet not clarified aetiology where the symptoms, voiding dysfunction and pelvic pain are difficult to alleviate. The aim of this study is to arrive at an understanding of how it influences the individual afflicted.

Ten men with CP/CPPS were interviewed about their situation. The interviews were transcribed and analysed using a phenomenological perspective. Results. The often severe symptoms influence well-being and a life in more or less constant fear of a relapse is described. A majority manages, despite the problems, to endure and conceal the problems. The situation can, however, become unbearable and force the man to seek solitude or lose his temper. Social isolation and restrictions at work and during recreational activities were thus reported by those more severely afflicted. Confirmation from the healthcare system that the disease is not life threatening and affirmation that they are not unwanted and neglected are essential.

Men with CP/CPPS are mostly able to live a normal life, although it is often difficult and the people around them are rarely given an insight into their world, where their existence is focused on attempts to obtain confirmation, control abrupt mood fluctuations and develop coping strategies. They have much in common with other patient groups afflicted by chronic pain, such as difficulties in performing at work and severe fatigue. More specific for CP/CPPS is the presence of additional symptoms, which individually can severely impair quality of life. Accepting the situation and developing coping strategies are consequently challenges for a man with CP/CPPS.

 

 

Jonsson K, Hedelin H.

Research and Development Centre and Department of Urology, Karnsjukhuset, Skovde, Sweden.

OBJECTIVE: Chronic abacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a disease of yet not clarified aetiology where the symptoms, voiding dysfunction and pelvic pain are difficult to alleviate. The aim of this study is to arrive at an understanding of how it influences the individual afflicted. 

MATERIALS AND METHODS: Ten men with CP/CPPS were interviewed about their situation. The interviews were transcribed and analysed using a phenomenological perspective. 

RESULTS: The often severe symptoms influence well-being and a life in more or less constant fear of a relapse is described. A majority manages, despite the problems, to endure and conceal the problems. The situation can, however, become unbearable and force the man to seek solitude or lose his temper. Social isolation and restrictions at work and during recreational activities were thus reported by those more severely afflicted. Confirmation from the healthcare system that the disease is not life threatening and affirmation that they are not unwanted and neglected are essential.

CONCLUSIONS: Men with CP/CPPS are mostly able to live a normal life, although it is often difficult and the people around them are rarely given an insight into their world, where their existence is focused on attempts to obtain confirmation, control abrupt mood fluctuations and develop coping strategies. They have much in common with other patient groups afflicted by chronic pain, such as difficulties in performing at work and severe fatigue. More specific for CP/CPPS is the presence of additional symptoms, which individually can severely impair quality of life. Accepting the situation and developing coping strategies are consequently challenges for a man with CP/CPPS.

Se: http://www.ncbi.nlm.nih.gov/pubmed/18615364

 

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Increased expression of CCAAT/enhancer-binding protein beta in proliferative inflammatory atrophy of the prostate: relation with the expression of COX-2, the androgen receptor, and presence of focal chronic inflammation

Augusti 2007.

Wang W, Bergh A, Damber JE

Department of Urology, Lundberg Laboratory for Cancer Research, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.

BACKGROUND: Proliferative inflammatory atrophy (PIA) in the prostate has been proposed to be a precursor to prostate cancer. CCAAT/enhancer-binding protein beta (C/EBPbeta) is an important transcription factor involved in cellular proliferation and differentiation. Activation of C/EBPbeta plays a crucial role during the initial stage of cyclo-oxygenase 2 (COX-2) induction by proinflammatory mediators. Overexpression of C/EBPbeta has been reported in several human tumors. Nevertheless, the C/EBPbeta expression and functions in human prostate tissue are basically unknown. 

METHODS: C/EBPbeta immunohistochemical staining was performed on 45 benign prostate hyperplasia (BPH) samples. The expression of C/EBPbeta in PIA lesions and normal-appearing acini was analyzed. In addition, by using double-IHC staining, C/EBPbeta expression and the association with chronic inflammatory cell density, co-expression of COX-2 and androgen receptor (AR) were also investigated.

RESULTS: C/EBPbeta was occasionally observed in normal-appearing prostate acini (4.9% +/- 6.7%, Mean +/- SD) but was clearly overexpressed in PIA lesions (81.8% +/- 16.4%) (P < 0.0001). Atrophic glands with T-lymphocyte and macrophage inflammation expressed higher level of C/EBPbeta. Furthermore, C/EBPbeta correlated significantly with COX-2 expression. Downregulation of the AR was common in PIA and was also related to the C/EBPbeta overexpression. 

CONCLUSIONS: The data demonstrated that chronic inflammation appeared to play roles in the induction of C/EBPbeta expression in prostate epithelium, which was in turn associated with increased COX-2 expression and AR downregulation. In combining with other molecular alteration in the epithelium of PIA, it is suggested that these cells might be a kind of intermediate cells and involved in the pathogenesis of prostate cancer. 

(c) 2007 Wiley-Liss, Inc.

Se http://www.ncbi.nlm.nih.gov/pubmed/17570496?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.
Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

PMID: 17570496 [PubMed - indexed for MEDLINE]

 

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Interstitiell cystit, molekylärbiologiska studier

Skapat av: Yr Logadottir, Sahlgrenska Universitetssjukhuset i Göteborg 2008-09-23

Interstitiell cystit (IC) är en kronisk invalidiserande sjukdom i urinblåsan. Etiologien till IC är ej känd. IC finns i två presentationer, klassisk och nonulcerös. Sjukdomen kännetecknas av svåra smärtor vid fyllnad av urinblåsan, som lättar vid tömning, vilket leder till starkt ökat antal toalettbesök natt och dag. Symptomen är desamma för de två presentationerna. Skillnaden är att sluttstadiet för klassisk IC är en skrumpblåsa pga destruktiv inflammation som ofta nödvändiggör avancerad rekonstruktiv kirurgi. Könsfördelningen är 10:1 kvinnor:män. För diagnos behöver patienten bl a undersökas i narkos med distension av urinblåsan, granskning av förändringar p.g.a. distension samt provtagning från blåsslemhinnan.

Vår forskningsgrupp har påvisat att klassisk och nonulcerös IC representerar olika sjukdomar. Klassisk IC är en äkta inflammatorisk sjukdom medan nonulcerös IC saknar tydliga inflammationstecken. Klassisk IC har bland många andra särdrag en dramatiskt hög frisättning av kväveoxid (NO) från blåsväggen samt markant infiltration av mastceller i blåsväggen inklusive slemhinnan. Vi anser bl.a. undersöka vilka celler som producerar NO och vilken isoform av enzymet kväveoxidsynthas (NOS) som är involverad. En ytterligare frågeställning är vilka olika inflammationsmarkörer som är relevanta. Tillgängliga data pekar på att vissa sådana torde vara mera intressanta, t.ex. TNF (Tumour Necrosis Factor), vissa interleukiner och cytokiner, samt tillväxtfaktorer som IGF-binding protein-3 och interleukin-6. Speciell uppmärksamhet har riktats mot epitelförändringen vid interstitiell cystit och faktorn APF (Anti Proliferative Factor).
Ett vidare delprojekt är att undersöka om förenklad diagnostik vid klassisk IC är möjlig. Vi avser här att använda 5-aminolevulinic acid (5-ALA) vid cystoskopi. Metoden är väl etablerad för blåscancerdiagnostik, är enkel och kan användas vid cystoskopi i lokalbedövning.
 

Målsättningen är att förbättra diagnostiken av en mycket plågsam sjukdom, den mest plågsamma benigna sjukdomen som drabbar urinblåsan, samt att analysera den specifika inflammationen vid klassik IC för att få en inblick i skeenden i inflammtionskaskaden. Förbättrad diagnostik kommer att leda till effektivare utvärdering av olika behandlingsalternativ och förhoppningsvis i förlängningen skapa ett fundament för att kunna behandla sjukdomen rationellt, kausalt, farmakologiskt.

Se http://www.fou.nu/is/sverige/document/12161

 

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Abolfazl Hosseini*, Ingrid Ehrèn, Peter Wiklund, Stockholm, Sweden

Introduction and Objective: Chronic prostatitis is an often used diagnosis in young men with chronic lower urinary tract symptoms. However in a great number of these patients no sign of infection in the prostate gland is found. Recent studies have shown that measurement of nitric oxide (NO) may be used to quantify the degree of inflammation in patients with asthma, colitis, rheumatoid arthritis and lower urinary tract inflammation. In the present study we measured the concentration of NO in the prostatic urethra in patients with the prostatitis syndrome.

Methods: Twenty patients with the prostatitis syndrome (age 42 plus, minus 8 years) were studied. The symptoms were evaluated with a prostatitis questioner developed by the University of Washington. The laboratory examination of urine was done as the recommended four-glass test and the expressed prostatic secretion (EPS) examined directly under microscope. The NO production in the prostatic urethra was measured by introducing a silicon catheter into the urethra. The catheter balloon was filled with room air and kept in the prostatic part of urethra for 5 minutes (5-min incubation yielded a 90% recovery of NO in control experiments). Transrectal ultrasonography was used to control the catheter balloon localization in the prostatic urethra. After incubation the air was injected into a chemiluminescence NO analyzer.

Results: Reagent strip urine analysis was negative in three voiding samples in all patients. Microscopic examination of expressed prostatic secretion showed >15 leukocytes per high power field (HPF) in 5 of 20 patients. In patients with >15 leukocytes/HPF the NO-levels were high (67 plus, minus 28 parts per billion, ppb), whereas in patients with <15 leukocytes/HPF the NO-levels were low (3 plus, minus 1, ppb). The 5 patients with increased intraprostatic NO-level had a median score of 7 (pain scale), 12 (voiding scale) and 2 (sexual dysfunction) in the prostatitis questioner, whereas the patients with low NO-level scored 11, 10 and 6 respectively.

Conclusions: Our results show that only 25% of the patients with chronic prostatitis showed evidence of inflammatory chronic abacterial prostatitis according to the "National Institutes of Health Classification of Prostatitis". In this group we found an increased NO formation in the prostatic urethra and increased number of leukocytes in EPS. Nitric oxide might be used as a marker to differentiate between the two subgroups of inflammatory and non-inflammatory chronic abacterial prostatitis.

Se även http://www.aerocrine.se/swedish/no_clinical_bladder.html 

 

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Scand J Urol Nephrol Suppl 1989; 123:1-36 

Wedren H: Department of Urology and Andrology, University of Umeå, Sweden

On chronic prostatitis with special studies of Staphylococcus epidermidis.

Patients with chronic prostatitis have an increased number of white blood cells in expressed prostatic secretion. Two groups can be separated; one is characterized by uropathogenic bacteria in expressed prostatic secretion and recurrent urinary tract infections, chronic bacterial prostatitis. In this group an immune response to the bacteria has been demonstrated. Patients belonging to the other group, non-bacterial prostatitis, have similar symptoms. Many harbour Gram-positive bacteria in a high number, often Staphylococcus epidermidis in expressed prostatic secretion. This bacterium is usually not considered in prostatitis in spite of extreme high numbers. The etiology of non-bacterial inflammations is thus unknown. Forty-three percent of the patients with chronic prostatitis had Gram-positive bacteria and13 % had Gram-negative in expressed prostatic secretion. Fortyfour per cent of patients referred with symptoms of prostatitis did not have any aerobic bacteria at the prostatic level in sufficient number for the diagnosis bacterial prostatitis according to Meares and Stamey and form thus a third group.  

Antibiotic treatment of patients with non-bacterial prostatitis reduced symptoms but also changed the bacterial flora in urethral and prostatic secretion in such a way that uropathogens were found after treatment. In a group of patients an immunologic response to Staph. Epidermidis was searched for by measuring complement components (C3c, C4c) as well as ceruloplasmin in serum and immunoglobulins (IgA, IgG) in seminal plasma. A specific ELISA method to estimate antibodies in serum against Staph. epidermidis was tested. No specific pattern separated patients from controls or patients with Gram-negative bacteria from patients with Gram-positive bacteria. Staphylococcus saprophyticus in cultures from men with prostatitis were more frequent in the third quarter of the year. The bacteria seemed to appear during or after antibiotic treatment but disappeared spontaneously during a follow-up period of six months.  

Treatment with the surfactant sodium pentosanpolysulphate (Elmiron), a heparinoid, given orally to patients with chronic prostatitis reduced concomitant pain in muscles and joints. The possibility of an altered host factor function in the polymorphonuclear leucocytes of patients with chronic non-bacterial prostatitis colonized with Staph. epidermidis was investigated. Chemotaxis, phagocytosis and intracellular killing were reduced in vitro and may to apart explain the bacteriological findings. Careful evaluations must thus be performed of earlier neglected factors to reach better knowledge of the chronic prostatitis.

ISOPs kommentar: Trots ovanstående forskningsresultat är inte denna medicin (Elmiron) godkänd i Sverige (endast i USA och Tyskland?) för allmänt bruk vid behandling av kronisk prostatit och interstitiell cystit. För att du som patient skall få tillgång till denna medicin, måste den behandlande läkaren därför göra en ansökan om tillstånd att använda denna genom en s.k. licensansökan. Denna lämnas till Apoteket för vidare handläggning. Vid ett ev. godkännande kommer medicinen att omfattas av högkostnadsskyddet för läkemedel.

För att skapa en bättre helhetsbild kring forskningen kring Elmiron, har jag valt att lägga till nedanstående abstract från AUA - meeting 2002. 

 

Effects of pentosan polysulfat sodium (PPS) in men with pelvic pain syndrome: A multicenter randomized, placebo-comtrolled study

J Curtis Nickel*, Kingston, ON, Canada; John Forrest, Tulsa, OK; Kevin M Tomera, Anchorage, AK; Jose Hernandez-Graulau, Peoria, IL; Timothy D Moon, Madison, WI; Anthony J Schaeffer, Chicago, IL; John N Krieger, Seattle, WA; Scott I Zeitlin, Los Angeles, CA; Robert Evans, Greensboro, NC; Daniel J Lama, San Bernardino, CA; Durwood Neal, Springfield, IL; Grannum Sant, Boston, MA.

Introduction and Objectives: Pentosan polysulfate sodium (PPS; 300 mg) has been effective in the treatment of interstitial cystitis, a disease associated with chronic pelvic pain in women. This double-blind, placebo-controlled, multicenter study evaluated the effects of PPS (900 mg) in men with NIH Category III Chronic Pelvic Pain Syndrome (CPPS).

Methods: Patients with NIH Category III CPPS were randomly assigned to receive 900 mg/day of PPS or placebo for 16 weeks. The primary endpoint was Clinical Global Improvement (CGI). The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) was also administered.

Results: Baseline demographics in the PPS (n=51) and placebo (n=49) groups were comparable, and 73% of patients completed the study. According to the CGI score, a significantly higher percentage of patients reported that their condition was moderately or markedly better following treatment with PPS (36.7%) than with placebo (17.8%; p=0.04). Quality of life based on the NIH-CPSI improved significantly with PPS compared with placebo (p=0.037). Although there was a greater numerical decrease in pain and urinary symptom domains of the NIH-CPSI with PPS compared with placebo, the differences did not approach statistical significance (p=0.21 and p=0.37, respectively). More than twice as many PPS patients had a > 50% decrease in total NIH-CPSI score compared with patients on placebo (21% vs. 9%). There was no difference in the number of patients who reported adverse events (71% in the PPS group vs. 64% in the placebo group) or the type of adverse events. More patients discontinued medication due to adverse events in the PPS group (24%) compared to placebo (8%). The most common adverse effects with PPS and placebo were diarrhea (13.7% vs 8.2%), nausea (13.7% vs 6.1%), and headache (11.8% vs 6.1%). The dose of PPS (900 mg) was three times the dose typically given for interstitial cystitis (300 mg).

Conclusions: This randomized, controlled trial demonstrated significant improvements in quality of life and significant global improvements in symptoms of chronic pelvic pain syndrome in men following treatment with PPS. Further studies are warranted to evaluate PPS for the treatment of CPPS in men.

 

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Journal of Urology 1996 Mar; 155(3): 958-60

Persson BE, Ronquist G, Department of Urology, University Hospital, Uppsala University, Sweden.

From NIH/NLM MEDLINE  NLM Citation ID: 96164640

PURPOSE: Chronic prostatitis is a common disease of the late teenage years, which affects patients for many years. In the majority of cases etiology is unknown but in some cases prostatitis is clearly caused by microorganisms that result from overuse of antibiotic drugs. We attempt to gain further knowledge about the etiology of the disease.

MATERIALS AND METHODS: We studied 56 patients with nonbacterial prostatitis in regard to whether urine reflux into the prostatic ducts was responsible for increased concentrations of creatinine, urate and white blood cells in expressed prostatic secretion. The patients were interviewed using a standard questionnaire.

RESULTS: A relationship was demonstrated between pain estimated in accordance with a scoring scale, and expressed prostatic secretion contents of white blood cells, urate and creatinine. 

CONCLUSIONS: These results provide further support of the role of reflux into the prostatic ducts as an underlying mechanism initiating a chemical inflammatory reaction. Urate appears to be the chemical agent eliciting this inflammatory.

 

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Antibacterial activity of human prostasomes.

Prostate 2000 Sep ??;44(4):279-86

Carlsson L, Påhlson C, Bergquist M, Ronquist G, Stridsberg M Department of Medical Sciences, Clinical Chemistry, Uppsala University,Sweden.

BACKGROUND: Prostasomes are prostate-derived organelles in semen exhibiting pluripotent properties. The present study deals with their possible antibacterial effects. 

METHODS: Antibacterial activity was assessed by growth inhibition of bacteria in an incubation medium containing prostasomes, after which the incubate was inoculated on cystine lactose electrolyte deficient agar (CLED) plates. In casesinvolving Bacillus megaterium, the effects were also documented ultrastructurally with scanning electron microscopy and atomic force microscopy. 

RESULTS: A dose-dependent growth inhibition was apparent, and a complete inhibition of growth was seen at a prostasome protein concentration of 30 microg/ml with Bacillus megaterium. Ultrastructurally, increasingly irregular contours and a loosening of the smooth surface were observed, combined with a fragmentation of the bacteria. Among 9 other bacterial strains tested, a complete growth inhibition by prostasomes was attained in 3 strains, while the other 6 were unaffected.

CONCLUSIONS: Our data suggest that prostasomes, or prostasome-derived proteins, are responsible for the antibacterial effects on Bacillus megaterium and some other bacterial strains. The results may serve as a basis of development of a new class of antibacterial drugs. 

PMID: 10951492, UI:?

 

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Symptomatic urethritis is more prevalent in men infected with Mycoplasma Genitalium than with Chlamydia trachomatis

L Falk1, H Fredlund2 and J S Jensen3 

1 Department of Dermatology and Venereology, Örebro University Hospital, Sweden

2 Department of Clinical Microbiology and Immunology, Örebro University Hospital, Sweden

3 Mycoplasma Laboratory, Statens Serum Institut, Copenhagen, Denmark.

Correspondence to: Dr Lars Falk Department of Dermatology and Venereology, Örebro University Hospital, SE-701 85 Örebro, Sweden; lars.falk@orebroll.se 

Objectives: To study the prevalence, symptoms, and signs of Mycoplasma genitalium and Chlamydia trachomatis infections in men attending a Swedish STD clinic and to study the criteria for urethritis. 

Methods: A cross sectional study among STD clinic attendees in Örebro, Sweden. Attendees were examined for microscopic urethritis and first void urine (FVU) was tested for M genitalium and C trachomatis.

Results: The prevalence of M genitalium and C trachomatis was 7% (34/512) and 12% (61/512), respectively. Dual infection was diagnosed in four men. In both infections 90% of the patients had signs of microscopic urethritis. M genitalium positive men had symptomatic urethritis significantly more often than those infected with C trachomatis (73% v 40%, RR 1.8; 95% CI 1.2 to 2.7). 63% of female partners of men infected with M genitalium were infected with M genitalium compared with chlamydial infection in 67% of female partners of men infected with C trachomatis. Non-chlamydial non-gonococcal urethritis without evidence of M genitalium infection was diagnosed in 180 men (35%). Symptoms and/or visible discharge were reported in 49% in this group. 

Conclusions: M genitalium is a common infection associated with symptomatic urethritis and with a high prevalence of infected sexual partners supporting its role as a sexually transmitted infection. 

 

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Ameliorative effect of allopurinol on nonbacterial prostatitis: a parallel double-blind controlled study

Persson BE; Ronquist G; Ekblom M.  Department of Urology, University Hospital, Uppsala, Sweden.

J Urol 1996 Mar;155(3):961-4 CITATION IDS: PMID: 8583618 UI: 96164641

ABSTRACT: PURPOSE: Nonbacterial prostatitis is a common problem in young men. It is a disease that is often recurrent and each episode lasts for several months. Different causative mechanisms of the disease have been discussed, including identified and unidentified microorganisms, stone formation and psychological factors. We have demonstrated in a previous study that urinary reflux (as shown by a high creatinine concentration in prostatic fluid) occurs to a varying extent into the prostatic ducts, and this reflux has been related to prostatic pain and urate concentration in expressed prostatic secretion.

MATERIALS AND METHODS: We performed a paralled double-blind controlled study of the objective and subjective effects of allopurinol on patients with nonbacterial prostatitis. Twenty patients received placebo, 18 received 300 mg. allopurinol daily and 16 received 600 mg allopurinol daily for 240 days. All patients began medication at the same time regardless of whether the disease was in an active state. No side effects were noted in the treatment groups.

RESULTS: Significant effects were noted on the concentrations of serum urate, urine urate, expressed prostatic secretion urate, expressed prostatic secretion xanthine and subjective discomfort.

CONCLUSIONS: Allopurinol has a significant, positive effect on nonbacterial prostatitis. It is safe and worthy of trial for all at least a 3- month period at each episode to relieve the symptoms of nonbacterial prostatitis.

 

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Pain in and health-related quality of life in a geographically defined population of men with prostate cancer

British Journal of Cancer, p 497-503, Volume 85, Number 4, August 2001

G. Sandblom, P. Carlsson, P. Sigsjö, E. Varenhorst

Abstract: In order to provide baseline data on pain and health-related quality of life, to explore factors predicting pain and reduced quality of life, and to find potentially undertreated cases in men with prostate cancer, we undertook a population-based questionnaire study. The questionnaire, which included the EuroQo1 instrument, the Brief Pain Inventory form and 8 specially designed questions, was sent to all men with prostate cancer in the county of Östergötland, Sweden. Of the 1442 men included in the study, 1243 responded to the questionnaire. Altogether 42% had perceived pain during the previous week and 26% stated their quality of life to be 50% or lower on a visual analogue scale. A high rating of health care availability and short time since diagnosis were found to significantly predict lower ratings of pain (P< 0.05). Pain was found to be a significant predictive factor for decreased quality of life together with high age, low rating of health care availability and palliative treatment (P< 0.05). 

In conclusion, assessment and treatment of pain is essential for a good quality of life in men with prostate cancer. The monitoring of prostate cancer patients should be individualized to fit the demands of the groups with the greatest need for support. Copyright 2001 Cancer Research Campaign.

ISOPs kommentar: Tyvärr är det vanligt att de som drabbas av svåra kroniska smärttillstånd p.g.a. kronisk prostatit eller interstitiell cystit inte får tillgång till en adekvat smärtlindring. Är detta p.g.a. okunskap hos den behandlande läkaren eller är det för att kronisk prostatit och interstitiell cystit normalt inte räknas som livshotande sjukdomar?

 

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In Vitro Pharmacodynamics of the New Ketolides HMR 3004 and HMR647 (Telithromycin) against Chlamydia pneumoniae

Antimicrobial Agents and Chemotherapy, July 2000, p. 1846-1849, Vol. 44, No. 7

Gustafsson,1, E. Hjelm,2 and O. Cars1 Departments of Infectious Diseases1 and Clinical Microbiology,2 University Hospital, Uppsala, Sweden.

Abstracts: The ketolides HMR 3004 and HMR 3647 (Telithromycin) are a new class of macrolides that have a potential clinical efficacy against intracellular pathogens. The objectives of this study were to investigate the MIC, minimum bactericidal concentration, and time-dependent killing of two Chlamydia pneumoniae strains of the two ketolides. The killing effect was also studied with a newly developed intracellular in vitro kinetic model. Furthermore, HMR 3647 was studied for the effect of a subinhibitory concentration of 0.5 times the MIC after a preexposure of 10 times the MIC during 12 h. The MICs for both strains were 0.0039 and 0.0156 mg/liter for HMR 3004 and HMR 3647, respectively. Killing with 10 times the MIC was time dependent, increasing from a 1-log-unit decrease in the number of inclusions per well at 48 h to a maximal effect of 2.8-log-unit decrease after 96 h. A preexposure of 10 times the MIC of HMR 3647 for 12 h followed by a subinhibitory concentration of 0.5 times the MIC increased the killing effect to a 1.2-log-unit reduction in inclusions per well. An exposure for 12 h gave poor reduction of inclusions, while a static dose of 10 times the MIC for 72 h showed a 2.2-log-unit reduction in inclusions per well. In the kinetic model, a small number of inclusions were detected after 72 h by one exposure of 10 times the MIC. Regrowth could not be detected after 120 h. The ketolides HMR 3004 and HMR 3647 have bactericidal activity and show a significant sub-MIC effect on the intracellular pathogen C. pneumoniae.

Du kan läsa mer om den här artikeln på följand URL: http://aac.asm.org/cgi/content/full/44/7/1846#B8

 

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Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: Sildenafil and papaverin generate inhibition

Published Online: 19 Mar 2002   Volume 51, Issue 1, 2002. Pages: 50-58

Copyright © 2002 Wiley-Liss, Inc.

Per I. Adolfsson 1 *, Christer Ahlstrand 2, Eberhard Varenhorst 2, Samuel P.S. Svensson 1.1Department of Medicine and Care, Division of Pharmacology, Faculty of Health Science, Linköping University, Linköping, Sweden. 2Department of Biomedicine and Surgery, Division of Urology, Faculty of Health Science, Linköping University, Linköping, Sweden

Background: The endogenous substance lysophosphatidic acid (LPA) has been found to generate proliferation of cultured smooth muscle cells (SMC). Therefore, the effect of LPA on human benign prostate hyperplasia (BPH) could be of interest.

Methods: The proliferative effect of LPA on cultured human prostatic SMC from specimens obtained at trans-urethral resection of the prostate (TURP) because of BPH, was analyzed by [3H]-thymidine and [35S]-methionine incorporation. In addition, LPA stimulated BPH SMC were treated with papaverin, forskolin, sildenafil or zaprinast, well known to increase the intracellular level of cAMP or cGMP. 

Results: LPA produced a dose-dependent increase in BPH SMC, both regarding DNA- and protein-synthesis with EC50 values of 3 and 10 M, respectively. Furthermore, both papaverin, a general phosphodiesterase inhibitor regarding cAMP hydrolyzes, and forskolin, an adenylyl cyclase stimulating agent, inhibited the LPA-stimulated DNA replication in a dose dependent manner with IC50 = 2.5, and 0.35 M, respectively. cGMP increasing agents, such as the NO-donors SIN-1 and SNAP, produced a weak anti-proliferative response. However, both phosphodiesterase 5 inhibitors sildenafil (Viagra®) and zaprinast efficiently blocked DNA replication. In addition, when the protein synthesis was examined, we found that the LPA response was significantly inhibited by forskolin and papaverin.

Conclusions: The major conclusion of this investigation is that the endogenous serum component LPA, is able to promote human BPH SMC growth. In addition, our study indicates that cyclic nucleotides can inhibit this effect. Future clinical studies will be needed to determine if different specific phosphodiesterase inhibitors per se or in combination could represent a new therapeutic possibility for the treatment of BPH. Prostate 51:50-58, 2002. 

 

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