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  • 1.
    Adolfsson, Per I
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Bloth, Björn
    Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Futurum Academy for Health and Care, Jönköping County Council, Sweden.
    Svensson, Samuel P S
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia.2015In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, no 3, p. 704.e15-704.e19Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the effects of zinc (Zn(2+)) concentrations on cultured benign prostatic hyperplasia (BPH) smooth muscle cell (SMC) proliferation.

    METHODS: The effects of Zn(2+) were studied in primary cultures of human BPH SMC, stimulated with either 10-μM lysophosphatidic acid (LPA) or LPA in combination with 100-nM testosterone. Deoxyribonucleic acid replication and protein synthesis using [(3)H]-thymidine and [(35)S]-methionine incorporation were measured. Furthermore, studies were performed to evaluate if Zn(2+) could potentiate the inhibitory effect of phosphodiesterase-5 blockers, on BPH SMC proliferation.

    RESULTS: Zn(2+) generated a bell-shaped concentration response, both regarding deoxyribonucleic acid replication and protein synthesis in cultured BPH SMC. Below a threshold value (approximately 200 μM), a significant mitogenic effect was seen, whereas higher concentrations inhibited SMC proliferation after stimulation with LPA. This effect was even more pronounced after stimulation of LPA in combination with testosterone. Moreover, phosphodiesterase-5 inhibitors, that is, sildenafil blocked LPA-stimulated BPH SMC proliferation. This antiproliferative effect, was significantly potentiated by coincubation with Zn(2+) in an additative manner.

    CONCLUSION: The bell-shaped concentration response of Zn(2+) on cultured BPH SMC proliferation suggests that changes in prostate Zn(2+) concentrations, during aging, diet, or inflammatory conditions, may be of importance in the pathogenesis of BPH.

  • 2.
    Andersson, Karl-Erik
    et al.
    Lund University Hospital, Sweden.
    Hedlund, Petter
    Lund University Hospital, Sweden.
    Pharmacologic perspective on the physiology of the lower urinary tract2002In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 60, no 5 Suppl 1, p. 13-20Article in journal (Refereed)
    Abstract [en]

    Myogenic activity, distention of the detrusor, and signals from the urothelium may initiate voiding. In the bladder, afferent nerves have been identified not only in the detrusor, but also suburothelially, where they form a plexus that lies immediately beneath the epithelial lining. Extracellular adenosine triphosphate (ATP) has been found to mediate excitation of small-diameter sensory neurons via P2X3 receptors, and it has been shown that bladder distention causes release of ATP from the urothelium. In turn, ATP can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, most probably, not only ATP but also a cascade of inhibitory and stimulatory transmitters and mediators are involved in the transduction mechanisms underlying the activation of afferent fibers during bladder filling. These mechanisms may be targets for future drugs. The central nervous control of micturition involves many transmitter systems, which may be suitable targets for pharmacologic intervention. gamma-Aminobutyric acid, dopamine, enkephalin, serotonin, and noradrenaline receptors and mechanisms are known to influence micturition, and potentially, drugs that affect these systems could be developed for clinical use. However, a selective action on the lower urinary tract may be difficult to obtain. Most drugs currently used for treatment of detrusor overactivity have a peripheral site of action, mainly the efferent (cholinergic) neurotransmission and/or the detrusor muscle itself. In the normal bladder, muscarinic receptor stimulation produces the main part of detrusor contraction, but evidence is accumulating that in disease states, such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis, as well as in the aging bladder, a noncholinergic activation via purinergic receptors may occur. If this component of activation is responsible not only for part of the bladder contractions, but also for the symptoms of the overactive bladder, it should be considered an important target for therapeutic interventions.

  • 3.
    He, Leye
    et al.
    The Third Xiangya Hospital, Central South University.
    Wang, Yong
    The Third Xiangya Hospital, Central South University.
    Long, Zhi
    The Third Xiangya Hospital, Central South University.
    Jiang, Chonghe
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Clinical Significance of IL-2, IL-10, and TNF-alpha in Prostatic Secretion of Patients With Chronic Prostatitis2010In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 75, no 3, p. 654-657Article in journal (Refereed)
    Abstract [en]

    Objectives

    To explore the clinical significance of interleukin-2 (IL-2), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in expressed prostatic secretions (EPS) of patients with different types of chronic prostatitis (CP).

    Methods

    Fifty-seven CP patients and 12 healthy males (controls) were investigated. The CP patients were evaluated through routine examination of urine, EPS, 2 glasses urine culture, and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score and classified by the NIH prostatitis diagnostic criteria. The levels of cytokines TNF-α, IL-10, and IL-2 in the EPS were measured by two-antibody enzyme-linked immunosorbent assay.

    Results

    CP patients fell into 3 groups: type II (n = 10), type IIIa (n = 26), and type IIIb (n = 21). EPS TNF-α and IL-10 levels were significantly higher in type II and type IIIa than in type IIIb and control groups. The levels of IL-2 were lower than control in all CP groups, but only type II was statistically different from the controls. In the CP patients, the level of TNF-α was positively related to the white blood cell counts (r = .77; P <.01), and the level of IL-10 was positively related to the NIH-CPSI scores (r = .55; P <.01).

    Conclusions

    Determination of variety expression of TNF-α, IL-10, and IL-2 in the EPS of CP patients may provide a potential indicator for clinical diagnosis classification and an indicator to evaluate the effect of treatment of CP.

  • 4.
    Jancke, Georg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Health and Developmental Care, Regional Cancer Centre.
    Chebil, Gunilla
    County Hospital, Helsingborg, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Bladder Wash Cytology at Diagnosis of Ta-T1 Bladder Cancer Is Predictive for Recurrence and Progression2012In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 80, no 3, p. 625-631Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To evaluate the effect of the bladder wash cytology finding at the primary diagnosis of Stage Ta-T1 urinary bladder cancer on recurrence and progression. less thanbrgreater than less thanbrgreater thanMETHODS The clinical and pathologic characteristics of all patients with primary Stage Ta-T1 urinary bladder cancer were prospectively registered. The data were divided according to the bladder wash cytology results at diagnosis. Multivariate analyses were performed to determine the influence of bladder wash cytology on recurrence and progression. less thanbrgreater than less thanbrgreater thanRESULTS The analysis included 768 evaluable patients with a mean follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). High-grade malignant bladder wash cytology was predictive for recurrence and progression (P andlt; .001 and P = .036, respectively). Other factors affecting recurrence were missing bladder wash cytology data, tumors size 16-30 mm and andgt;30 mm, Stage T1 tumor category, and multiplicity (P = .008, P = .006, P andlt; .001, P = .002, and P andlt; .001, respectively). Progression was also associated with T1 tumor category, local recurrence, and primary concomitant carcinoma in situ (P andlt; .001, P andlt; .001, and P = .024, respectively). less thanbrgreater than less thanbrgreater thanCONCLUSION High-grade malignant bladder wash cytology at the primary diagnosis was predictive for recurrence and progression. This could be taken into account in designing future follow-up schedules.

  • 5.
    Kedia, George T.
    et al.
    Hannover Medical School, Germany.
    Ückert, Stefan
    Hannover Medical School, Germany; Institute for Biochemical Research and Analysis, Germany.
    Oelke, Matthias
    Hannover Medical School, Germany.
    Sonnenberg, Joachim E.
    Institute for Biochemical Research and Analysis, Germany.
    Sohn, Michael
    AGAPLESION Markus Hospital, Germany.
    Kuczyk, Markus A.
    Hannover Medical School, Germany.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. University Vita Salute San Raffaele, Italy.
    Expression and Distribution of Phosphodiesterase Isoenzymes in the Human Male Urethra2015In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, no 4, p. 964.e1-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To investigate the expression and distribution of phosphodiesterase (PDE) isoenzymes PDE1A, PDE2A, PDE4A, PDE4B, and PDE5A in human urethral tissue. METHODS Specimens of penile urethra were obtained from male subjects who had undergone male-to-female sex reassignment surgery. Using immunohistochemistry (immunofluorescence), the occurrence of PDE1A, PDE2A, PDE4A, PDE4B, and PDE5A, the neuronal nitric oxide synthase, calcitonin gene-related peptide, and vasoactive intestinal polypeptide was examined in urethral sections. Cytosolic supernatants prepared from isolated human urethral tissue were subjected to Western blot analysis using specific anti-PDE antibodies. RESULTS Immunosignals specific for PDE1A, 4A, 4B, and 5A were observed in the urethral smooth musculature. The smooth muscle bundles were seen innervated by slender nerve fibers, characterized by the expression of the neuronal nitric oxide synthase, calcitonin gene-related peptide, and vasoactive intestinal polypeptide. The expression of the PDE isoenzymes mentioned was confirmed by Western blotting. CONCLUSION The results provide evidence for a significance of both the cyclic adenosine monophosphate and cyclic guanosine monophosphate signaling in the control of human urethral smooth muscle. The selective inhibition of PDE isoenzymes might represent a pharmacologic option to influence the function of smooth musculature in the human outflow region.

  • 6.
    Klaff, Rami
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Faculty of Medicine and Health Sciences.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Sandblom, Gabriel
    Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Hospital, Huddinge, Sweden.
    The Long-term Disease-specific Mortality of Low-risk Localized Prostate Cancer: A Prospective Population-based Register Study Over Two Decades2016In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 91, p. 77-82Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To identify prognostic factors, and to estimate the long-term disease-specific and annual disease-specific mortality rates of low-risk prostate cancer patients from the early prostate-specific antigen (PSA) era. PATIENTS AND METHODS We studied data extracted from the Southeast Region Prostate Cancer Register in Sweden, on 1300 patients with clinically localized low-risk tumors, T1-2, PSA level amp;lt;= 10 mu g/L and Gleason scores 2-6 or World Health Organization Grade 1, diagnosed 1992-2003. The Cox multivariate regression model was used to evaluate factors predicting survival. Prostate cancer death rates per 1000 person-years were estimated for 4 consecutive follow-up time periods: 0-5, 5-10, 10-15, and 15+ years after diagnosis. RESULTS During the follow-up of overall survivors (mean 10.6 years; maximum 21.8 years), 93 patients (7%) died of prostate cancer. Cancer-specific survival was 0.98 (95% confidence interval [CI] 0.97-0.99), 0.95 (95% CI 0.93-0.96), 0.89 (95% CI 0.86-0.91), and 0.84 (95% CI 0.80-0.88), 5, 10, 15, and 20 years after diagnosis. The 5-year increases in cancer-specific mortality were statistically significant (P amp;lt;. 001). Patients with PSA amp;gt;= 4 mu g/L managed initially with watchful waiting and those aged 70 years or older had a significantly higher risk of dying from their prostate cancer. CONCLUSION The long-term disease-specific mortality of low-risk localized prostate cancer is low, but the annual mortality rate from prostate cancer gradually increases. This indicates that some tumors slowly develop into lethal cancer, particularly in patients 70 years or older with a PSA level amp;gt;= 4 mu g/L. (C) 2016 Elsevier Inc.

  • 7.
    Oelke, M
    et al.
    University of Amsterdam.
    Hedlund, Petter
    Lund University Hospital.
    Albrecht, K
    Hannover Medical School.
    Ellinghaus, P
    Bayer HealthCare AG.
    Stief, CG
    Ludwig-Maximilians-University.
    Jonas, U
    Hannover Medical School.
    Andersson, KE
    Lund University Hospital.
    Uckert, S
    Hannover Medical School.
    Expression of cAMP and cGMP-phosphodiesterase isoenzymes 3, 4, and 5 in the human clitoris: Immunohistochemical and molecular biology study2006In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 67, no 5, p. 1111-1116Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Only a little research has focused on the evaluation of female sexual function. With sexual stimulation, the clitoris becomes engorged with blood and tumescent. Nevertheless, only little is known about the significance of the cyclic nucleotide-mediated signal transduction in the control of this process. We sought to elucidate the presence of the phosphodiesterase (PDE) isoenzymes 3, 4, and 5 in the human clitoris using immunohistochemical and molecular biology methods.

    METHODS: Thin sections of clitoral specimens were incubated with primary antibodies directed against PDE isoenzymes 3, 4, and 5. Next, the sections were incubated with either Texas red or fluorescein isothiocyanate-labeled secondary antibodies, and visualization was done using laser microscopy. The expression of mRNA encoding for various PDE isoenzymes was evaluated using reverse transcriptase polymerase chain reaction.

    RESULTS: Immunofluorescence indicating the presence of PDE4 (cyclic adenosine monophosphate-PDE) was observed in the nonvascular smooth musculature of the corpus cavernosum clitoris, sinusoidal endothelial and subendothelial layers, and nerve fibers innervating the tissue. Immunoreactivity specific for PDE5 (cyclic guanosine monophosphate-PDE) was limited to the smooth muscle of the clitoral erectile tissue. The fluorescein isothiocyanate reaction indicating the expression of PDE3 (cyclic adenosine monophosphate-PDE) was registered to a certain degree only in the clitoral epidermis. In the reverse transcriptase polymerase chain reaction studies, a predominant expression of mRNA encoding for PDE1A was registered, but only small amounts of mRNA encoding for PDE4 and PDE5 were detected.

    CONCLUSIONS: Our results have demonstrated the presence of cyclic adenosine monophosphate-PDE and cyclic guanosine monophosphate-PDE in the human clitoris and may indicate a regulatory function of these enzymes in the cyclic nucleotide-mediated control of smooth muscle tone.

  • 8.
    Rittmaster, Roger
    et al.
    GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
    Hahn, Robert G.
    Södertälje Hospital, Sweden.
    Ray, Paul
    Cook County Hospital, Chicago, Illinois, USA.
    Shannon, Jennifer B.
    GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
    Wurzel, Rafael
    Grove Hill Medical Center, New Britain, Connecticut, USA.
    Effect of dutasteride on intraprostatic androgen levels in men with benign prostatic hyperplasia or prostate cancer2008In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 72, no 4, p. 808-812Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Dutasteride exerts its beneficial effects on the prostate through suppression of intraprostatic dihydrotestosterone (DHT). The aim of this analysis was to assess the effects of the approved dose of dutasteride (0.5 mg/d), given for 2 weeks to 4 months, on the serum and intraprostatic DHT and testosterone levels in 3 randomized studies.

    METHODS: Intraprostatic androgen levels were measured in benign prostatic tissue collected during transurethral resection of the prostate (benign prostatic hyperplasia studies, n = 256) or radical prostatectomy (prostate cancer study, n = 51), performed after 2 weeks, or 1, 3, or 4 months of treatment with dutasteride or with placebo or surgery alone. The serum androgen levels were assessed at the same points during treatment. Data from the control groups were pooled to provide 1 comparison group.

    RESULTS: Dutasteride reduced the intraprostatic DHT levels by 83%, 90%, 92%, and 93% after 2 weeks and 1, 3, and 4 months of treatment, respectively, compared with placebo/surgery alone. Dutasteride reduced the serum DHT levels from baseline by 84% at 2 weeks and by approximately 90% at 1, 2, 3, and 4 months compared with a 5.2% increase in the control group. The decrease in DHT levels with dutasteride was accompanied by a reciprocal increase in the serum and intraprostatic testosterone levels. However, the intraprostatic testosterone levels in the dutasteride groups generally remained lower than the intraprostatic DHT levels in the control group.

    CONCLUSIONS: The results of our study have shown that dutasteride provides near-maximal suppression of both serum and intraprostatic DHT levels in men with benign prostatic hyperplasia or prostate cancer at all points assessed.

  • 9.
    Robinson, David
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sandblom, Gabriel
    Department of Surgery, University Hospital of Lund, Lund, Sweden.
    Johansson, Robert
    Oncological Center, Umeå University Hospital, Umeå, Sweden.
    Garmo, Hans
    Uppsala Clinical Research Center, University Hospital, Uppsala, Sweden.
    Aus, Gunnar
    Department of Urology, Sahlgrens University Hospital, Göteborg, Sweden.
    Hedlund, Per Olov
    Department of Urology, Karolinska Hospital, Stockholm, Sweden.
    Varenhorst, Eberhard
    Linköping University, Department of Clinical and Experimental Medicine, Urology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    PSA Kinetics Provide Improved Prediction of Survival in Metastatic Hormone-Refractory Prostate Cancer2008In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 72, no 4, p. 903-907Article in journal (Refereed)
    Abstract [en]

    Objectives: To assess the value of prostate-specific antigen (PSA) kinetics in predicting survival and relate this to the baseline variables in men with metastatic hormone-refractory prostate cancer (HRPC).

    Methods: The data from 417 men with HRPC were included in a logistic regression model that included hemoglobin, PSA, alkaline phosphatase, Soloway score, and performance status pain analgesic score at baseline. The posttreatment variables included the PSA level halving time after the start of treatment, PSA level at nadir, interval to nadir, PSA velocity (PSAV), PSA doubling time after reaching a nadir, patient age, and treatment. These variables were added to the baseline model, forming new logistic regression models that were tested for net reclassification improvement.

    Results: The area under the receiver operating characteristics curve for the baseline model was 0.67. Of all variables related to PSA kinetics, the PSAV was the best predictor. The addition of PSAV to the baseline model increased the area under the receiver operating characteristics curve to 0.81. Only a moderate increase in the area under the receiver operating characteristics curve (0.83) was achieved by combining the baseline model in a multivariate model with PSAV, PSA doubling time, interval to nadir, and patient age at diagnosis of HRPC.

    Conclusions: The PSAV alone gave a better prediction of survival value than all other PSA kinetics variables. By combining PSAV with the variables available at baseline, a better ground for treatment decision-making in men with HRPC can be achieved.

  • 10.
    Sandblom, Gabriel
    et al.
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Dufmats, Monika
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Long-term survival in a swedish population-based cohort of men with prostate cancer2000In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 56, no 3, p. 442-447Article in journal (Refereed)
    Abstract [en]

    Objectives. To study the long-term survival of patients with prostate cancer, determine the risk factors for prostate cancer death, and investigate the outcome of initially untreated localized prostate cancer and incidentally detected tumors.

    Methods. The survival of 813 patients in a population-based cohort of patients with prostate cancer in Linköping, Sweden, diagnosed from 1974 to 1986, was analyzed.

    Results. At 10, 15, and 20 years after diagnosis, the prostate cancer-specific survival rate of men with localized, initially untreated, prostate cancer was 85.0% (95% confidence interval [CI], 79.0% to 91.0%), 80.0% (95% CI, 72.5% to 87.5%), and 62.6% (95% CI, 43.0% to 82.2%). Age 70 years or older, advanced stage, and poor differentiation were risk factors associated with an increased risk of prostate cancer death. At 10 years, the prostate cancer-specific survival rate among men with localized tumors treated by expectancy was 90% (95% CI, 84% to 97%) for grade 1 tumors, 74% (95% CI, 60% to 89%) for grade 2 tumors, and 59% (95% CI, 29% to 90%) for grade 3 tumors. For patients with incidentally detected tumors, the grade of malignancy was a more important risk factor than tumor volume.

    Conclusions. Patients with localized tumors have a favorable prognosis, even without initial treatment. However, when deciding on therapy, the grade of malignancy should be taken into account, as it has a great influence on survival. We did not see a tendency toward increased mortality when the patients were followed up for longer than 10 years after diagnosis.

  • 11. Schelin, S
    et al.
    Geertsen, U
    Walter, S
    Spångberg, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Duelund-Jacobsen, J
    Kroyer, K
    Hjertberg, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Vatne, V
    Richthoff, J
    Nordling, J
    Feedback microwave thermotherapy versus TURP/prostate enucleation surgery in patients with benign prostatic hyperplasia and persistent urinary retention: A prospective, randomized, controlled, multicenter study2006In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 68, no 4, p. 795-799Article in journal (Refereed)
    Abstract [en]

    Objectives: To assess the clinical efficacy of ProstaLund Feedback Treatment (PLFT) using the CoreTherm device versus transurethral resection of the prostate (TURP) and prostate enucleation surgery. Methods: We performed a prospective, randomized, controlled, multicenter study of 120 patients with symptomatic benign prostatic hyperplasia and persistent urinary retention requiring an indwelling catheter or clean intermittent catheterization. The primary efficacy variables were success in catheter removal and symptom improvement. Results: Of the 120 patients, 79% and 88% were catheter free after PLFT and surgery, respectively. The bother score (quality-of-life question) decreased from 4.6 in both groups before treatment to 1.4 in the PLFT group and 0.8 in the surgery group at 6 months of follow-up. The peak urinary flow rate was 13.4 mL/s after PLFT and 18.0 mL/s after surgery. The mean catheterization time was 34 days in the PLFT group and 5 days in the surgery group. Conclusions: PLFT is an effective alternative to surgical treatment in this group of catheterized patients. The risk of severe complications is reduced using PLFT, and an excellent treatment option can thereby be offered to this high-risk patient group who earlier could be treated only with lifelong catheterization. © 2006 Elsevier Inc. All rights reserved.

  • 12.
    Song, Bo
    et al.
    Southwest Hospital, Third Military Medical University.
    Jiang, Chonghe
    Hunan Normal University Medical College.
    Wang, Yongquan
    Southwest Hospital, Third Military Medical University.
    Lu, Yang
    Southwest Hospital, Third Military Medical University.
    Li, Longkun
    Southwest Hospital, Third Military Medical University.
    Newly found prostate-bladder neural reflex in rats--possible mechanism for      voiding dysfunction associated with prostatitis/pelvic pain2009In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 74, no 6, p. 1365-1369Article in journal (Refereed)
    Abstract [en]
    Objectives

    To demonstrate the existence of a prostate-bladder neural reflex that might help clarify a neurologic mechanism for voiding dysfunction associated with chronic prostatitis/chronic pelvic pain syndrome.

    Methods

    Experiments were performed on anesthetized adult male Wistar rats. Repeated cystometry was used to study the changes in urinary bladder behavior induced by injecting formalin into the prostate. The pathway of a prostate-bladder reflex was identified by recording the electromyographic (EMG) response of the detrusor to electrical stimulation of the prostate, after saline or lidocaine injections into the prostate, and transection of the prostate nerves.

    Results

    Intraprostatic formalin injection induced significant changes in the parameters of cystometry. Electrical stimulation of the prostate consistently evoked a bladder EMG response. Intraprostatic lidocaine injection increased the delay and reduced the amplitude of this EMG response. The bladder EMG response was not affected by transection of the cervical spinal cord nor by just cutting the sympathetic chain; however, it was suppressed by resection of the sympathetic chain and by transection of the ipsilateral L6-S3 nerve roots.

    Conclusions

    A prostate-bladder reflex is proposed, and the lumbosacral spinal cord is assumed to be the primary center of the reflex. These findings might help determine the therapeutic approach to voiding dysfunction in patients with chronic prostatitis/chronic pelvic pain syndrome.

  • 13.
    Uckert, S
    et al.
    Hannover Medical School.
    Oelke, M
    University of Amsterdam.
    Waldkirch, E
    Hannover Medical School.
    Stief, CG
    Ludwig-Maximilian-University.
    Albrecht, K
    Hannover Medical School.
    Troger, HD
    Hannover Medical School.
    Jonas, U
    Hannover Medical School.
    Andersson, KE
    Lund University Hospital.
    Hedlund, Petter
    Lund University Hospital.
    Cyclic adenosine monophosphate and cyclic guanosine monophosphate-phosphodiesterase isoenzymes in human vagina: Relation to nitric oxide synthase isoforms and vasoactive intestinal polypeptide-containing nerves2005In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 65, no 3, p. 604-610Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the distribution of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) phosphodiesterases (PDEs) in relation to nitric oxide synthase isoforms and vasoactive intestinal polypeptide (VIP) in specimens of the human vagina. Nitric oxide and VIP, mediating biologic signals through cGMP and cAMP, have been assumed to be involved in the control of vaginal smooth muscle.

    METHODS: Immunohistochemical techniques were applied to sectioned specimens of the human vaginal wall to evaluate the presence of the PDE isoenzymes 3, 4, 5, and 10 in relation to neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and VIP.

    RESULTS: Immunoreactivity (IR) for cAMP-degrading PDE-4 was observed in the vaginal nonvascular smooth musculature, as well as in the wall of subepithelial arteries. VIP-IR nerves innervated the smooth muscle portion of the vaginal wall and also formed a subepithelial network. Immunoreactivity specific for PDE-5 was also registered in vascular and nonvascular vaginal smooth muscle. Immunosignals for eNOS were detected in the endothelial lining of arteries containing PDE-5-IR smooth muscle cells. These arteries were supplied by nNOS-IR nerve fibers. PDE-10-IR smooth muscle cells were located in muscle bundles of the vaginal wall.

    CONCLUSIONS: Our study revealed immunoreactivity specific for PDE-4, PDE-5, and PDE-10 in the vascular and nonvascular smooth muscle of the vagina. Immunosignals for PDE-4 and PDE-5 were also observed in close proximity to nNOS-IR or VIP-IR nerve fibers or to eNOS-IR endothelial cells. The distribution of PDEs may indicate a role of these enzymes in the control of the function of the human vagina.

  • 14.
    Waldkirch, Eginhard
    et al.
    Hannover Medical School, Germany.
    Uckert, Stefan
    Hannover Medical School, Germany.
    Sigl, Katja
    MorphoSys AG, Martinsried, Germany.
    Langnaese, Kristina
    Otto-von-Guericke-University, Magdeburg, Germany.
    Richter, Karin
    Otto-von-Guericke-University, Magdeburg, Germany.
    Stief, Christian G.
    Ludwig-Maximilians-University, Munich, Germany.
    Kuczyk, Markus A.
    Hannover Medical School, Germany.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Expression of cAMP-dependent protein kinase isoforms in the human prostate: functional significance and relation to PDE42010In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 76, no 2, p. 515.e8-515.e14Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the expression of isoforms of the cyclic AMP (cAMP)-dependent protein kinase (cAK) in the transition zone of the human prostate and the functional significance of the enzyme in the control of prostate smooth muscle.

    METHODS: Using Western blot analysis and immunohistochemistry, the expression and distribution in the prostate of cAKIalpha, cAKIbeta, cAKIIalpha, and cAKIIbeta in relation to alpha-actin and the phosphodiesterase PDE4 (types A and B) were investigated. The effects of the cAK inhibitor Rp-8-CPT-cAMPS on the reversion of the adrenergic tension of isolated prostate tissue induced by forskolin, rolipram, sodium nitroprusside (SNP), and tadalafil were examined by means of the organ bath technique.

    RESULTS: Immunosignals specific for cAKIalpha, cAKIIalpha, and cAKIIbeta were observed in the smooth musculature and glandular structures of the prostate. Double stainings revealed the colocalization of alpha-actin and PDE4 with the cAK isoforms. The expression of the cAK isoforms was confirmed by Western blot analysis. The relaxation of the tension induced by norepinephrine brought about by forskolin, rolipram, SNP, and tadalafil was significantly attenuated by Rp-8-CPT-cAMPS.

    CONCLUSIONS: The colocalization of smooth muscle alpha-actin and PDE4 with cAK, as well as the results from the organ bath experiments, provide further evidence for a pivotal role of the cAMP-dependent signaling in the regulation of prostate smooth muscle contractility. Compounds interacting with the cAMP/cAK pathway might represent a new therapeutic avenue to treat symptoms of benign prostatic hyperplasia and lower urinary tract symptomatology.

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