liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 31 of 31
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Aizawa, Naoki
    et al.
    University of Tokyo, Japan.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Fuellhase, Claudius
    University of Munich, Germany.
    Ito, Hiroki
    University of Tokyo, Japan.
    Homma, Yukio
    University of Tokyo, Japan.
    Igawa, Yasuhiko
    University of Tokyo, Japan .
    Inhibition of Peripheral FAAH Depresses Activities of Bladder Mechanosensitive Nerve Fibers of the Rat2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 3, p. 956-963Article in journal (Refereed)
    Abstract [en]

    Purpose: FAAH degrades endocannabinoids and fatty acid amides. FAAH inhibition reduces micturition frequency and counteracts bladder overactivity in rats. We studied the effects of the peripherally active selective FAAH inhibitor URB937, and the CB1 and CB2 receptor antagonists rimonabant and SR144528, respectively, on single unit afferent activity of primary bladder afferents in rats. Materials and Methods: Female Sprague Dawley (R) rats were anesthetized. Single unit afferent activity of A delta or C-fibers from the L6 dorsal roots was recorded during bladder filling before and after URB937 administration with or without rimonabant or SR144528. Drugs (1 mg/kg) were given intravenously. FAAH, CB1 and CB2 expression, and expression of the sensory marker CGRP in the L6 dorsal root ganglion were compared by immunofluorescence. Results: A total of 102 single afferent fibers (48 A delta and 54 C-fibers) were isolated from 57 rats. URB937 decreased single unit afferent activity of C-fibers to a mean +/- SEM of 78% +/- 9% and of A delta-fibers to a mean of 67% +/- 7% while increasing bladder compliance to a mean of 116% +/- 3%. The effects of URB937 on single unit afferent activity and bladder compliance were counteracted by rimonabant or SR144528. Rimonabant increased single unit afferent activity of each fiber type but SR144528 affected only A delta-fiber activity. CGRP positive L6 dorsal root ganglion neurons showed strong FAAH, CB1 and CB2 staining. Conclusions: To our knowledge we report for the first time that inhibiting peripheral FAAH depresses the Ad and C-fiber activity of primary bladder afferents via CB1 and CB2 receptors. CB antagonists alone exerted facilitatory effects on single unit afferent activity during bladder filling in rats. The endocannabinoid system may be involved in physiological control of micturition as regulators of afferent signals.

  • 2.
    Andersson, Patiyan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Kolaric, Aleksandra
    Departments of Pathology, Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Departments of Urology, Örebro University Hospital, Örebro, Sweden.
    Kirrander, Peter
    Departments of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Karlsson, Mats G.
    Departments of b Pathology, Örebro University Hospital, Örebro, Sweden.
    PIK3CA, HRAS and KRAS gene mutations in human penile cancer2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 5, p. 2030-2034 Article in journal (Refereed)
    Abstract [en]

    Purpose: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways.

    Materials and Methods: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors.

    Results: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma.

    Conclusions: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.

  • 3.
    Berrum-Svennung, Ingela
    et al.
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    Granfors, Torvald
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Jahnson, Staffan
    Boman, Hans
    Lasarettet, Dept Urol, Alingsas, Sweden.
    Holmang, Sten
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    A single instillation of epirubicin after transurethral resection of bladder tumors prevents only small recurrences2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 1, p. 101-105Article in journal (Refereed)
    Abstract [en]

    Purpose: We studied whether a single instillation of epirubicin after transurethral bladder tumor resection would influence the interval to and size of the first recurrence. Materials and Methods: A total of 404 patients from 13 hospitals were randomized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors. Results: Of 155 evaluable patients in the epirubicin group 79 (51.0%) had recurrence compared to 95 of 152 (62.5%) in the placebo group (p = 0.04). Of the recurrences 63.3% were small (1 to 5 mm). Tumor size was unknown in 5 patients. Of 79 patients with recurrence in the epirubicin arm 33 (42.9%) vs 29 (31.5%) of 95 in the placebo arm had larger (more than 5 mm) first recurrences (p = 0.12). Approximately half of the patients with first recurrences were treated as outpatients and the other half spent a total of 145 days in the hospital with no difference between the groups. Conclusions: We confirmed the results of previous studies showing that 8.5 patients must be treated with a single instillation to prevent I recurrence. Furthermore, our data may indicate that only small recurrences are prevented, which could easily be fulgurated using local anesthesia at followup cystoscopy. The benefit of single instillations can be questioned if this finding is confirmed by others.

  • 4.
    Drake, Marcus J
    et al.
    Tyne Micturution Research Group, School of Surgical Sciences, University of Newcastle, United Kingdom..
    Hedlund, Petter
    Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
    Andersson, Karl-Erik
    Department of Clinical Pharmacology, University of Lund, Sweden..
    Brading, Alison F
    Hussain, Iqbal
    Fowler, Clare
    Landon, David N
    Morphology, phenotype and ultrastructure of fibroblastic cells from normal and neuropathic human detrusor: absence of myofibroblast characteristics.2003In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 169, no 4, p. 1573-6Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Fibroblasts are functionally diverse and fibroblastic cells with smooth muscle-like characteristics (myofibroblasts) regulate smooth muscle activity in certain tissues. The presence of myofibroblasts has been reported in the bladder with important implications for normal function and detrusor overactivity. We assessed fibroblastic cell characteristics to discern features suggesting a myofibroblast phenotype in normal or neuropathic human detrusor.

    MATERIALS AND METHODS: A total of 25 control samples were obtained from cadaveric organ donors or patients with a mean age of 42.3 years investigated for hematuria and compared with samples from 18 patients with a mean age of 37.4 years with neurogenic detrusor overactivity. Morphology, phenotypic expression of various markers and the ultrastructure of each fibroblastic cell visible in multiple sections from each specimen was evaluated by 2 independent assessors.

    RESULTS: Fibroblastic cells were observed throughout the smooth muscle and connective tissue. They were located peripherally on muscle fascicles and had a polar stellate appearance with processes ramifying in interfascicular planes and muscle. They possessed vimentin-like immunoreactivity and weak c-kit-like immunoreactivity but not desmin or alpha-smooth muscle actin-like immunoreactivity. Ultrastructurally they showed dilated rough endoplasmic reticulum with a moderately electron dense amorphous content and prominent golgi complexes. Nuclei had clumped peripheral heterochromatin. There were extensive flattened processes that lacked basal laminae. There was no specific contact with nerve fibers or smooth muscle. Neuropathic bladder samples did not differ overtly from those of controls.

    CONCLUSIONS: The detrusor possesses an extensive network of fibroblastic cells and processes. No evidence of myofibroblast differentiation was discerned in normal or neuropathic detrusor, although a minority subpopulation or regional variability in cellular phenotype could not be excluded.

  • 5.
    Drake, Marcus J
    et al.
    Urophysiology Research Group , School of Surgical Sciences, University of Newcastle, United Kingdom.
    Hedlund, Petter
    Department of Clinical Pharmacology, Lund University Hospital, Sweden.
    Harvey, Ian J
    Urophysiology Research Group , School of Surgical Sciences, University of Newcastle, United Kingdom.
    Pandita, Raj Kumar
    Department of Clinical Pharmacology, Lund University Hospital, Sweden.
    Andersson, Karl-Erik
    Department of Clinical Pharmacology, Lund University Hospital, Sweden.
    Gillespie, James I
    Urophysiology Research Group , School of Surgical Sciences, University of Newcastle, United Kingdom.
    Partial outlet obstruction enhances modular autonomous activity in the isolated rat bladder.2003In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 170, no 1, p. 276-279Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Autonomous bladder activity can take the form of localized micromotions (MMs), suggesting that the detrusor may be arranged into component modules, of which each is capable of contracting autonomously. We examined MMs in isolated whole rat bladder and the effects of partial bladder outlet obstruction as a model of detrusor overactivity (DO) to ascertain whether altered modular activity could be an etiological factor in DO.

    MATERIALS AND METHODS: A total of 12 adult female Sprague-Dawley rats underwent obstruction or sham operation for 1 or 4 weeks. Bladders were microsurgically removed and mounted in whole organ tissue baths. Recordings of intravesical pressure and simultaneous registration of intramural contractions were performed under standardized conditions.

    RESULTS: Prior to filling MMs took the form of localized contractions near the vesicoureteral junction in sham operated animals and multifocal microcontractions in obstructed animals. Intravesical volume increases were associated with a change in localized MMs to propagated contraction waves. In sham operated animals stretch resulted in increased MM frequency but decreased amplitude. After obstruction stretch elicited highly coordinated MMs and enhanced intravesical pressure transmission. The time since surgery did not alter observations in the sham or obstructed group.

    CONCLUSIONS: Detrusor muscle in isolated bladders under conditions modeling urine storage may have a functional modular arrangement with the basolateral region most active prior to filling. Peripheral factors determining intravesical pressure include the number of modules active, coordination and intramural tension at other sites. After bladder outlet obstruction more modules are active at baseline and their coordination is enhanced by stretch, leading to increased pressure fluctuations. Such changes may contribute to the development of DO.

  • 6.
    Fuellhase, Claudius
    et al.
    University of Munich, Germany .
    Russo, Andrea
    San Raffaele University, Italy .
    Castiglione, Fabio
    San Raffaele University, Italy .
    Benigni, Fabio
    San Raffaele University, Italy .
    Campeau, Lysanne
    Wake Forest University, NC USA .
    Montorsi, Francesco
    San Raffaele University, Italy .
    Gratzke, Christian
    University of Munich, Germany .
    Bettiga, Arianna
    San Raffaele University, Italy .
    Stief, Christian
    University of Munich, Germany .
    Andersson, Karl-Erik
    Wake Forest University, NC USA .
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Spinal Cord FAAH in Normal Micturition Control and Bladder Overactivity in Awake Rats2013In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 189, no 6, p. 2364-2370Article in journal (Refereed)
    Abstract [en]

    Purpose: We assessed whether spinal inhibition of the cannabinoid degrading enzyme FAAH would have urodynamic effects in normal rats and rats with bladder overactivity induced by partial urethral obstruction or prostaglandin E2. We also determined the expression of FAAH, and the cannabinoid receptors CB1 and CB2 in the sacral spinal cord. Materials and Methods: We used 44 rats for functional (cystometry) and Western blot experiments. The FAAH inhibitor oleoyl ethyl amide (3 to 300 nmol) was administered intrathecally (subarachnoidally) or intravenously. The expression of FAAH and CB1/CB2 receptors was determined by Western blot. Results: Oleoyl ethyl amide given intrathecally affected micturition in normal rats and rats with bladder overactivity but effects were more pronounced in the latter. In normal rats oleoyl ethyl amide only decreased micturition frequency, while it decreased frequency and bladder pressures in rats with bladder overactivity. Intravenous oleoyl ethyl amide (3 to 300 nmol) had no urodynamic effect. FAAH and CB1/CB2 receptors were expressed in the rat sacral spinal cord. The expression of CB1/CB2 receptors but not FAAH was higher in obstructed than in normal rats. Conclusions: FAAH inhibition in the sacral spinal cord by oleoyl ethyl amide resulted in urodynamic effects in normal rats and rats with bladder overactivity. The spinal endocannabinoid system may be involved in normal micturition control and it appears altered when there is bladder overactivity.

  • 7. Geirsson, Gudmundur
    et al.
    Lindström, Sivert
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Fall, Magnus
    The bladder cooling reflex and the use of cooling as stimulus to the lower urinary tract.1999In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 162, p. 1890-1896Article in journal (Refereed)
  • 8.
    Gladh, Gunilla
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Lindström, Sivert
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Outcome of the bladder cooling test in children with neurogenic bladder dysfunction1999In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 161, no 1, p. 254-258Article in journal (Refereed)
    Abstract [en]

    Purpose

    We evaluated the diagnostic use of the bladder cooling test in children with neurogenic bladder dysfunction.

    Materials and Methods

    We performed 201 bladder cooling tests in 65 female and 43 male patients 5 days to 17 years old, including 70 with myelomeningocele, 12 with high spinal lesions, 9 with sacral spinal lesions and 17 with encephalopathy of various types. At the end of routine cystometry we rapidly infused body temperature saline to approximately a third of cystometric capacity, followed by the same volume of saline at 4 to 8C. The test was considered positive when a detrusor contraction greater than 30 cm. water was evoked by the cold but not the warm infusion.

    Results

    The bladder cooling test was positive in 37 children younger than 4 years, at which age it is normally positive. The test was negative in only 2 patients, indicating a complete lower motor neuron lesion. It was positive in 34 of the 57 children older than 6 years, at which age it should be negative. Thus, the positive bladder cooling test confirmed neurogenic bladder dysfunction. Four of the 20 children with a negative test voided normally, while the remainder had no voiding contractions, suggesting a nonfunctional spinal sacral reflex arch to the bladder.

    Conclusions

    The bladder cooling test is a simple, reliable assessment that may serve to demonstrate a functional sacral reflex arch in young patients without voiding contractions or confirm a suspected lower motor neuron lesion. It may be used longitudinally to demonstrate changes in bladder function with growth.

  • 9.
    Gladh, Gunilla
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Mattsson, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Lindström, Sivert
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Outcome of the bladder cooling test in children with nonneurogenic bladder problems2004In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 172, no 3, p. 1095-1098Article in journal (Refereed)
    Abstract [en]

    Purpose:

    The bladder cooling test (BCT) engages a primitive neonatal spinal reflex that becomes suppressed by descending signals in older children and may reappear with suprasacral lesions. We assessed the outcome of the BCT in a large group of children with nonneurogenic bladder problems.

    Materials and Methods:

    The BCT was evaluated in a consecutive series of 178 girls and 106 boys, 1 month to 18 years old with bladder problems without overt neurology. The test was performed at the end of routine cystometry by a rapid control infusion of body warm saline followed, after fluid evacuation, by the same volume of cold saline (3 to 10C). The test was considered positive if a detrusor contraction greater than 30 cm H2O was evoked by the cold but not the warm fluid.

    Results:

    Most children younger than 4 years had a history of pyelonephritis (29 of 34) and/or had vesicoureteral reflux (grade IV to V in 26 of 34). For those younger than 2 years 87% of the BCTs were positive while only 21% of the tests were positive in 2 to 3-year-old children. Most children older than 4 years had idiopathic urge incontinence, and greater than 50% of the BCTs were positive in the youngest (less than 6 years) with a gradual decline to 0% at age 13 years.

    Conclusions:

    Conversion of positive to negative BCTs at about age 2 years presumably represents normal maturation while positive tests in older incontinent children suggest delayed maturation of the central neuronal control of the bladder.

  • 10.
    Gomez-Pinilla, Pedro J
    et al.
    - Spanien.
    Gomez, Maria F
    Lund.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Swärd, Karl
    Lund.
    Hellstrand, Per
    Lund.
    Camell, Pedro J
    Spanien.
    Pozo, Maria J
    Spanien.
    Andersson, Karl-Erik
    Lund/North Carolina.
    Effect of melatonin on age associated changes in guinea pig bladder function2007In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 177, p. 1558-1561Article in journal (Refereed)
    Abstract [en]

    Purpose

    The incidence of urinary incontinence increases with age but the cause and effect relationship between aging and altered bladder function is poorly understood. It was suggested that melatonin can ameliorate negative effects induced by aging by its free radical scavenging activity and its ability to decrease oxidative stress. We investigated the changes in bladder function evoked by aging and the possible benefits of melatonin treatment on age related bladder disturbances.

    Materials and Methods

    Bladder function was assessed using cystometry in conscious, freely moving female guinea pigs. Animals were grouped according to age as young adults (4 months old) and senescents (18 to 20 months old). A group of senescent animals were treated with 2.5 mg kg−1 day−1 melatonin for 21 days.

    Results

    Aging led to increased detrusor activity, as demonstrated by short micturition intervals, decreased bladder capacity and spontaneous contractions during the filling phase. During the voiding phase aged animals showed lower micturition pressures than young adults. Melatonin counteracted the cystometric changes in senescent animals and restored micturition parameters to those of young adults.

    Conclusions

    These results show that in guinea pigs aging induces detrusor overactivity. Melatonin treatment improved age induced changes in bladder function. If similar effects can be demonstrated in humans, melatonin treatment may be a new approach to decrease the impact of age related bladder disorders.

  • 11.
    Hammar, Mats
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Frisk, Jessica
    Linköping University, Department of health and environment. Linköping University, Faculty of Health Sciences.
    Grimsås, Ö
    Department of Surgery, County Hospital, Ludvika, Sweden.
    Höök, M
    Department of Surgery, County Hospital, Ludvika, Sweden.
    Spetz, Anna-Clara
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Wyon, Yvonne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Acupuncture treatment of vasomotor symptoms in men with prostatic carcinoma: A pilot study1999In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 161, no 3, p. 853-856Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Most men who undergo castration therapy for prostatic carcinoma will have vasomotor symptoms that usually persist for years. Vasomotor symptoms are elicited from the thermoregulatory center, possibly due to a decrease in hypothalamic opioid activity induced by low sex steroid concentrations. Acupuncture treatment in women, which stimulates hypothalamic opioid activity, alleviates vasomotor symptoms. We report on men treated with acupuncture for relief of vasomotor symptoms after castration therapy.

    MATERIALS AND METHODS: We asked 7 men with vasomotor symptoms due to castration therapy to receive acupuncture treatment 30 minutes twice weekly for 2 weeks and once a week for 10 weeks. Effects on flushes were recorded in logbooks.

    RESULTS: Of the 7 men 6 completed at least 10 weeks of acupuncture therapy and all had a substantial decrease in the number of hot flushes (average 70% after 10 weeks). At 3 months after the last treatment the number of flushes was 50% lower than before therapy. Therapy was discontinued after 10 weeks because of a femoral neck fracture in 1 man and after 3 weeks due to severe back pain in 1.

    CONCLUSIONS: Acupuncture may be a therapeutic alternative in men with hot flushes after castration therapy and merits further evaluation.

  • 12.
    Hannan, Johanna L.
    et al.
    The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
    Albersen, Maarten
    Urological Research Institute, San Raffaele Hospital, Vita-Salute University, Milan, Italy.
    Kutlu, Omer
    The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
    Gratzke, Christian
    Department of Urology, Ludwig-Maximilians-University, Munich, Germany.
    Stief, Christian G.
    Department of Urology, Ludwig-Maximilians-University, Munich, Germany.
    Burnett, Arthur L.
    The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
    Lysiak, Jeffrey J.
    Department of Urology, University of Virginia, Charlottesville, Virginia, USA.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Bivalacqua, Trinity J.
    The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
    Inhibition of Rho-Kinase Improves Erectile Function, Increases Nitric Oxide Signaling and Decreases Penile Apoptosis in a Rat Model of Cavernous Nerve Injury2013In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 189, no 3, p. 1155-1161Article in journal (Refereed)
    Abstract [en]

    Purpose: Bilateral cavernous nerve injury results in up-regulation of ROCK signaling in the penis. This is linked to erectile dysfunction in an animal model of post-prostatectomy erectile dysfunction. We evaluated whether daily treatment with the ROCK inhibitor Y-27632 (Tocris Bioscience, Ellisville, Missouri) would prevent erectile dysfunction in a rat model of bilateral cavernous nerve injury.Materials and Methods: Sprague-Dawley(R) rats underwent surgery to create sham (14) or bilateral (27) cavernous nerve injury. In the injury group 13 rats received treatment with Y-27632 (5 mg/kg twice daily) and 14 received vehicle. At 14 days after injury, rats underwent cavernous nerve stimulation to determine erectile function. Penes were assessed for neuronal and nitric oxide synthase membrane-endothelial nitric oxide synthase. ROCK2 was assessed by Western blot. Cyclic guanosine monophosphate was determined by enzyme-linked immunosorbent assay. Cavernous homogenates were tested for ROCK and protein kinase G enzymatic activity. Penile apoptosis was evaluated using the Apostain technique (Alexis, San Diego, California). Data were analyzed on ROCK using ANOVA and the t test.Results: While erectile function was decreased in rats with bilateral cavernous nerve injury, daily administration of Y-27632 improved erectile responses. Injury decreased neuronal and nitric oxide synthase membrane-endothelial nitric oxide synthase but ROCK2 was significantly increased. Y-27632 treatment restored neuronal nitric oxide synthase, nitric oxide synthase membrane-endothelial nitric oxide synthase and cyclic guanosine monophosphate levels, and protein kinase G activity. Treatment significantly decreased ROCK2 protein and ROCK activity. There were significantly fewer apoptotic cells after treatment than in injured controls.Conclusions: These results provide evidence for up-regulation of the RhoA/ROCK signaling pathway with detrimental effects on erectile function after bilateral cavernous nerve injury. ROCK inhibition improved erectile dysfunction associated with bilateral cavernous nerve injury by preserving penile nitric oxide bioavailability and decreasing penile apoptosis.

  • 13.
    Hedlund, Petter
    et al.
    Lund University Hospital.
    Holmquist, F.
    Lund University Hospital.
    Hedlund, H.
    Lund University Hospital.
    Andersson, K. E.
    Lund University Hospital.
    Effects of nicorandil on human isolated corpus cavernosum and cavernous artery1994In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 151, no 4, p. 1107-1113Article in journal (Refereed)
    Abstract [en]

    Nitric oxide (NO) released from nonadrenergic-noncholinergic (NANC) nerves seems to be a principal mediator of the relaxation of penile erectile tissue necessary for erection, and drugs acting by release of NO have been shown to produce erection when injected intracorporeally into impotent patients. By producing hyperpolarization, K+ channel openers are effective in relaxing isolated penile erectile tissue from rabbit and man, and can produce tumescence and erection when injected intracorporeally into animals. Nicorandil is classified as a K+ channel opener, but it also acts as a donor of NO. In the present study, the effects of nicorandil on isolated preparations from human corpus cavernosum (CC) and deep cavernous artery (Acc) were compared with those of cromakalim (K+ channel opener) and SIN-1 (NO donor). Nicorandil produced a concentration-dependent relaxation of CC and Acc preparations. The relaxations obtained at the highest nicorandil concentration used (10(-4) M.) were 75 +/- 3% and 66 +/- 4% in CC preparations contracted by noradrenaline and endothelin-1, respectively. The corresponding effects in Acc preparations were 70 +/- 14% and 73 +/- 5%. Glibenclamide (blocking ATP-dependent K+ channels) significantly reduced the nicorandil-induced relaxation in CC, but not in Acc. Methylene blue (believed to block soluble guanylate cyclase) reduced nicorandil's relaxant effect in CC, although statistical significance was not obtained. NG-nitro-L-arginine 10(-4) M. (NO synthase inhibitor) did not significantly influence the effect of nicorandil on precontracted preparations in either tissue. In CC preparations contracted by electrical field stimulation, nicorandil and cromakalim concentration dependently inhibited the responses. This effect was significantly counteracted by glibenclamide. It is concluded that nicorandil is effective in relaxing human CC chiefly by its K+ channel opening action, and to some extent by its ability to release NO. For nicorandil's relaxing effect on Acc, ATP dependent K+ channels seem to be of limited importance. If effective in impotent patients, the drug may represent a new, interesting approach to the treatment of erectile dysfunction.

  • 14.
    Hedlund, Petter
    et al.
    Departments of Clinical Pharmacology and Pathology, Lund University Hospital, Lund, Sweden.
    Ny, Lars
    Departments of Clinical Pharmacology and Pathology, Lund University Hospital, Lund, Sweden.
    Alm, Per
    Departments of Clinical Pharmacology and Pathology, Lund University Hospital, Lund, Sweden.
    Andersson, Karl-Erik
    Departments of Clinical Pharmacology and Pathology, Lund University Hospital, Lund, Sweden.
    Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase.2000In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 164, no 3 Part 1, p. 868-875Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To characterize the distribution of cholinergic nerves in the human corpus cavernosum (CC) and spongiosum (CS) using antibodies to the vesicular acetylcholine transporter (VAChT), and to compare this distribution to those of other transmitters/mediators or transmitter/mediator generating enzymes (heme oxygenases: HO-1 and HO-2; neuronal and endothelial NO synthases: nNOS and eNOS; vasoactive intestinal polypeptide: VIP; and tyrosine hydroxylase: TH), and to investigate NO- and carbon monoxide (CO)-mediated effects.

    MATERIALS AND METHODS: Immunocytochemistry, confocal laser scanning microscopy, radioimmunoassay, and functional in vitro studies.

    RESULTS: Along strands of smooth muscle in the CC and CS, rich numbers of VAChT-, nNOS-, VIP-, TH-, and very few HO-1-immunoreactive (-IR) nerve fibers were observed. Immunoreactivities for VAChT and nNOS, VAChT and VIP, and nNOS and VIP, were generally found in the same varicose nerve terminals. TH-IR nerve fibers or terminals did not contain immunoreactivities for VAChT, NOS or VIP. In the endothelium lining penile arteries, immunoreactivities for eNOS, HO-1, and HO-2 were detected. Single endothelial cells, lining the sinusoidal walls of the CC and CS, were found also to contain eNOS and HO-immunoreactivities. Noradrenaline (NA)-contracted preparations of CC and CS were relaxed by NO, CO, carbachol and by electrical stimulation of nerves. Inhibition of NO synthesis abolished electrically- and carbachol-induced relaxation. In NA-activated strips, relaxation induced by exogenously applied NO, but not those by CO, were accompanied by increases in intracellular levels of cyclic GMP.

    CONCLUSIONS: VAChT, NOS and VIP are found in the same nerve terminals within the human CC and CS, suggesting that these terminals comprise a distinct population of parasympathetic, cholinergic nerves. Endothelially derived NO and the HO/CO system may have a complementary role in penile erection.

  • 15.
    Hedlund, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Streng, Tomi
    Lund.
    Lee, Tack
    Lund.
    Andersson, Karl-Erik
    Lund/North Carolina.
    Effects of Tolterodine on Afferent Neutransmission in Normal and Resiniferatoxin Treated conscious Rats2007In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 178, p. 326-331Article in journal (Refereed)
    Abstract [en]

    Purpose

    The beneficial effects of antimuscarinics on detrusor overactivity and overactive bladder syndrome are exerted during bladder filling, when there is no parasympathetic outflow from the spinal cord. We tested the hypothesis that, if tolterodine exerts some of its effects on afferent nerves, the functional elimination of C-fiber afferents should affect the actions of the drug on urodynamic parameters.

    Materials and Methods

    The study was performed in normal female Sprague Dawley rats and rats treated with resiniferatoxin to eliminate vanilloid sensitive afferent nerves. Tolterodine was given intravenously to normal and resiniferatoxin treated animals. To test if tolterodine at the doses used affects efferent neurotransmission the drug was given to normal and resiniferatoxin treated animals in which detrusor activity was induced by apomorphine.

    Results

    In resiniferatoxin treated animals (0.3 mg kg−1 subcutaneously) the mean micturition interval and volume, and mean residual volume increased significantly compared to those in controls. Baseline and micturition pressures in control and resiniferatoxin treated animals were similar, whereas threshold pressures were higher in resiniferatoxin treated animals. In controls 10 μg kg−1 tolterodine administered intravenously increased the mean micturition interval, bladder capacity and micturition volume. In resiniferatoxin treated rats 1 and 10 μg kg−1 tolterodine increased the mean micturition interval, bladder capacity and micturition volume. Subcutaneous administration of 100 μg kg−1 apomorphine induced detrusor overactivity in all rats. The AUC of intravesical pressure during the initial 10 minutes from the start of detrusor overactivity showed no difference between normal and resiniferatoxin treated rats with or without tolterodine pretreatment.

    Conclusions

    Tolterodine increased the micturition interval and bladder capacity in controls and in resiniferatoxin treated animals, suggesting that these effects were exerted independently of resiniferatoxin sensitive afferents. Tolterodine did not decrease the contractile effects of apomorphine at the doses used, suggesting that the drug had no effect on efferent neurotransmission during voiding.

    Purpose

    The beneficial effects of antimuscarinics on detrusor overactivity and overactive bladder syndrome are exerted during bladder filling, when there is no parasympathetic outflow from the spinal cord. We tested the hypothesis that, if tolterodine exerts some of its effects on afferent nerves, the functional elimination of C-fiber afferents should affect the actions of the drug on urodynamic parameters.

    Materials and Methods

    The study was performed in normal female Sprague Dawley rats and rats treated with resiniferatoxin to eliminate vanilloid sensitive afferent nerves. Tolterodine was given intravenously to normal and resiniferatoxin treated animals. To test if tolterodine at the doses used affects efferent neurotransmission the drug was given to normal and resiniferatoxin treated animals in which detrusor activity was induced by apomorphine.

    Results

    In resiniferatoxin treated animals (0.3 mg kg−1 subcutaneously) the mean micturition interval and volume, and mean residual volume increased significantly compared to those in controls. Baseline and micturition pressures in control and resiniferatoxin treated animals were similar, whereas threshold pressures were higher in resiniferatoxin treated animals. In controls 10 μg kg−1 tolterodine administered intravenously increased the mean micturition interval, bladder capacity and micturition volume. In resiniferatoxin treated rats 1 and 10 μg kg−1 tolterodine increased the mean micturition interval, bladder capacity and micturition volume. Subcutaneous administration of 100 μg kg−1 apomorphine induced detrusor overactivity in all rats. The AUC of intravesical pressure during the initial 10 minutes from the start of detrusor overactivity showed no difference between normal and resiniferatoxin treated rats with or without tolterodine pretreatment.

    Conclusions

    Tolterodine increased the micturition interval and bladder capacity in controls and in resiniferatoxin treated animals, suggesting that these effects were exerted independently of resiniferatoxin sensitive afferents. Tolterodine did not decrease the contractile effects of apomorphine at the doses used, suggesting that the drug had no effect on efferent neurotransmission during voiding.

  • 16.
    Hemdan, Tammer
    et al.
    University Hospital Uppsala, Sweden.
    Johansson, Robert
    Umeå University Hospital, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Hellström, Pekka
    University Central Hospital, Oulu, Finland.
    Tasdemir, Ilker
    Central Hospital of Rogaland, Stavanger, Norway.
    Malmström, Per-Uno
    University Hospital Uppsala, Sweden.
    5-Year Outcome of a Randomized Prospective Study Comparing bacillus Calmette-Guerin with Epirubicin and Interferon-alpha 2b in Patients with T1 Bladder Cancer2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, no 5, p. 1244-1249Article in journal (Refereed)
    Abstract [en]

    Purpose: In a multicenter, prospectively randomized study we evaluated the 5-year outcomes of bacillus Calmette-Guerin alone compared to a combination of epirubicin and interferon-alpha 2b in the treatment of patients with T1 bladder cancer. Materials and Methods: Transurethral resection was followed by a second resection and bladder mapping. Stratification was for grade and carcinoma in situ. Followup entailed regular cystoscopy and cytology during the first 5 years. The end points assessed in this analysis were recurrence-free survival, time to treatment failure and progression, cancer specific survival and prognostic factors. Results: The study recruited 250 eligible patients. The 5-year recurrence-free survival rate was 38% in the combination arm and 59% in the bacillus Calmette-Guerin arm (p = 0.001). The corresponding rates for the other end points were not significantly different, as free of progression 78% and 77%, treatment failure 75% and 75%, and cancer specific survival 90% and 92%, respectively. The type of treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant carcinoma in situ was not predictive of failure of bacillus Calmette-Guerin therapy. An independent factor for treatment failure was remaining T1 stage at second resection. Conclusions: Bacillus Calmette-Guerin was more effective than the tested combination therapy. The currently recommended management with second resection and 3-week maintenance bacillus Calmette-Guerin entails a low risk of cancer specific death. More aggressive treatment in patients with infiltrative tumors at second resection might improve these results. In particular, concomitant carcinoma in situ was not a predictive factor for poor outcome after bacillus Calmette-Guerin therapy.

  • 17.
    Hemdan, Tammer
    et al.
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Malmström, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Department of Surgical Sciences, Uppsala University, Uppsala.
    Segersten, Ulrika
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Emmprin expression predicts response and survival following cisplatin containing chemotherapy for bladder cancer: A validation study2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, no 6, p. 1575-1581Article in journal (Refereed)
    Abstract [en]

    Purpose Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response. Materials and Methods Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry. Results Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p <0.001). The values for cancer specific survival were 76% and 56%, respectively (p <0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p = 0.23) or cancer specific survival (55% vs 51%, p = 0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials. Conclusions Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression. © 2015 American Urological Association Education and Research, Inc.

  • 18.
    Jahnson, Staffan
    et al.
    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.
    Sandblom, Dag
    Orebro University Hospital.
    Holmang, Sten
    Sahlgrens University Hospital.
    A Randomized Trial Comparing 2 Doses of Polidocanol Sclerotherapy for Hydrocele or Spermatocele2011In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 186, no 4, p. 1319-1323Article in journal (Refereed)
    Abstract [en]

    Purpose: Polidocanol sclerotherapy for hydrocele or spermatocele combines high efficiency with low morbidity, but the optimal dose is not known. We compared the efficacy and morbidity of 2 or 4 ml polidocanol sclerotherapy for hydrocele or spermatocele. less thanbrgreater than less thanbrgreater thanMaterials and Methods: From 1993 to 2005 a double-blind randomized clinical trial was conducted using 2 or 4 ml polidocanol (30 mg/ml) for sclerotherapy of hydrocele/spermatocele in 224 evaluable patients at 3 university hospitals. Fluid was evacuated and 2 or 4 ml polidocanol was administered by a nurse, with the amount injected concealed from others present. At 3-month followup morbidity was ascertained using a questionnaire completed by the patients. Fluid recurrence was determined clinically and generally re-treated. less thanbrgreater than less thanbrgreater thanResults: After the first treatment, cure was observed in 59% and 47% in the 4 and the 2 ml group, respectively (p = 0.04). More patients in the 4 ml group had complications (31% vs 18%, p = 0.04). Complications were mostly of low or moderate intensity and seldom required medication. After 1 to 4 treatments 200 of 224 patients (89%) were cured and another 10 (5%) had small amounts of residual fluid, with no difference between the groups. Of the patients with hydroceles/spermatoceles larger than 175 ml, 58% and 34% were cured after the first treatment in the 4 and 2 ml groups, respectively (p = 0.012), with no differences in complications between the groups. less thanbrgreater than less thanbrgreater thanConclusions: Polidocanol sclerotherapy was effective for the treatment of hydrocele or spermatocele in our patients, with 94% satisfactory results after 1 to 4 treatments. A dose of 4 ml was superior to 2 ml, particularly for larger hydroceles/spermatoceles.

  • 19.
    Lee, Dawn
    et al.
    BresMed, England.
    Kildegaard Nielsen, Sandy
    BresMed, England.
    van Keep, Marjolijn
    BresMed, Netherlands.
    Andersson, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Ferring Int PharmaScience Centre, Denmark.
    Greene, Damien
    Sunderland Royal Hospital, England.
    Quality of Life Improvement in Patients Treated with Degarelix versus Leuprorelin for Advanced Prostate Cancer2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 193, no 3, p. 839-846Article in journal (Refereed)
    Abstract [en]

    Purpose: We used responses to questionnaires included in the CS21 degarelix trial and published mapping algorithms to address the paucity of evidence for health related quality of life in patients with advanced hormone dependent prostate cancer treated with degarelix. Materials and Methods: We measured health related quality of life in 610 patients enrolled in the CS21 trial using SF-12 (R) and EORTC QLQ-C30. Based on responses to these questionnaires we estimated patient utility using 4 published mapping algorithms. Utility was tested for relationships with aspects of the symptom and side effect burden that may be affected by degarelix treatment, that is prostate specific antigen progression and adverse events. Results: Average utility in patients without prostate specific antigen progression or an adverse event was 0.742, similar to previously published utilities for nonprogressed prostate cancer states. Prostate specific antigen progression was associated with a utility decrement of between 0.062 and 0.134 depending on the mapping algorithm used. Of adverse events considered in our analysis musculoskeletal events were associated with the greatest effects on patient utility with a decrement of between 0.029 and 0.086. The 4 mapping algorithms generated similar utility estimates, although values derived from SF-12 were consistently lower than those derived from EORTC QLQ-C30. Conclusions: Prostate specific antigen progression status and the incidence of treatment and disease related adverse events result in significant decrements to patient health related quality of life. By slowing prostate specific antigen progression degarelix may improve patient utility and the health related quality of life burden.

  • 20.
    Lee, Tack
    et al.
    Korea.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Newgreen, Donald
    USA.
    Urodynamic effects of a novel EP, receptor antagonist in normal rats and rats with bladder outlet obstruction2007In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 177, p. 1562-1567Article in journal (Refereed)
    Abstract [en]

    Purpose

    Prostaglandin E2 and its EP1 receptor were suggested as endogenous modulators of bladder function in the normal physiological state and under pathophysiological conditions. We investigated if the new EP1 receptor antagonist PF-2907617-02 would influence the regulation of normal micturition in rats, and if it affects bladder function in animals with partial bladder outlet obstruction.

    Materials and Methods

    The study was performed in normal female Sprague-Dawley rats and in rats with moderate, experimentally induced bladder outlet obstruction 2 weeks in duration. All animals underwent continuous cystometry in the awake state. PF-2907617-02 was given intravenously at doses of 0.1 and 1.0 mg/kg–1 in normal rats, and at 1.0 mg/kg–1 in bladder outlet obstructed animals. In a group of normal rats detrusor overactivity was produced by intravesical instillation of prostaglandin E2.

    Results

    In normal rats PF-2907617-02 (1 mg/kg–1) significantly increased bladder capacity, micturition volume and the micturition interval but it had no effect on other urodynamic parameters. The lower dose of PF-2907617 (0.1 mg/kg–1) showed no effect. Intravesical prostaglandin E2 (50 μM) induced detrusor overactivity. The antagonist significantly decreased the stimulatory effects of prostaglandin E2 at 0.1 and 1.0 mg/kg–1. In obstructed animals PF-2907617-02 significantly increased the micturition interval but not bladder capacity and residual volume. The drug also decreased the frequency and amplitude of nonvoiding contractions.

    Conclusions

    EP1 receptor is involved in initiation of the micturition reflex in normal rats and in animals with bladder outlet obstruction. It may also contribute to the generation of detrusor overactivity after bladder outlet obstruction. Thus, EP1 receptor antagonists may have potential as treatment for detrusor overactivity in humans.

  • 21.
    Lindström, Sivert
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Mazières, Leonor
    Jiang, Chonghe
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Inhibition of the bladder cooling reflex in the awake state: An experimental study in the cat2004In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 172, no 5 I, p. 2051-2053Article in journal (Refereed)
    Abstract [en]

    Purpose: We assessed the bladder cooling reflex in the awake cat. The bladder cooling reflex is consistently observed in anesthetized adult cats but not in awake, neurologically normal humans. This discrepancy could indicate a state dependant control of the reflex or a species difference. This study was designed to differentiate between these alternatives. Materials and Methods: Under ketamine-xylazine 5 animals had an indwelling catheter inserted into the bladder. The cooling reflex was tested by injections of cold saline into the bladder (4C to 8C), lowering its wall temperature to about 30C to 32C. The volume used (5 ml) was subthreshold for the Aδ micturition reflex, as confirmed by control injections of body warm saline. The procedure was repeated with the animals fully awake and it was well tolerated by all of them. Reflex responses were assessed by induced bladder pressures. Results: Typical bladder cooling reflexes with peak pressures greater than 3 kPa were evoked in all cats when in narcotic sleep (group mean ± CI 7.4 ± 3.1 kPa). No such reflexes were elicited when the animals were awake (2.0 ± 1.0 kPa). The difference was significant at the level of individual animals. Conclusions: The bladder cooling reflex is suppressed in adult cats during wakefulness, as in humans. This state dependent control of the bladder cooling reflex adds to its resemblance to the extensor plantar response (Babinski's sign).

  • 22.
    Malmqvist, U
    et al.
    University of Lund.
    Hedlund, Petter
    University of Lund.
    Swärd, K
    University of Lund.
    Andersson, KE
    University of Lund.
    Female pig urethral tone is dependent on Rho guanosine triphosphatases and Rho-associated kinase2004In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 171, no 5, p. 1955-1958Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Circular smooth muscle of the urethra generates spontaneous myogenic tone of relevance for the maintenance of continence. We tested if Rho guanosine triphosphatases (GTPases) and Rho-associated kinase (ROK) are involved in the generation of urethral tone.

    MATERIALS AND METHODS: Small circular strips of female pig urethra were dissected out and mounted for recording isometric force. The effect of pharmacological agents known to modulate the activity of Rho GTPases or ROK was examined. The intracellular calcium concentration was measured using fura-2.

    RESULTS: Urethral tone was abolished by removing extracellular calcium or by adding the calcium antagonist felodipine. The decrease in force was closely related to a decrease in intracellular calcium concentration, indicating that tone depends on membrane associated mechanisms. Toxin B, which inactivates Rho GTPases, and Y 27632, which inhibits ROK, completely abolished tone in the female pig urethra. The latter effect occurred without any change in the intracellular calcium concentration.

    CONCLUSIONS: The results suggests that urethral tone depends on activity in G-protein coupled pathways and inhibition of this activity is sufficient for urethral tone relaxation. Thus, to our knowledge a new pathway in the generation of urethral tone, which might be acted on by autonomic nerves during micturition, has been identified.

  • 23.
    Mattsson, Sven
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Gladh, Gunilla
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Lindström, Sivert
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Relative filling of the bladder at daytime voids in healthy school children2003In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 170, no 4 I, p. 1343-1346Article in journal (Refereed)
    Abstract [en]

    Purpose

    We analyzed how healthy children use their bladder storage capacity during everyday life, and how transient changes in diuresis affect bladder filling and voiding intervals.

    Materials and Methods

    Voided volumes and times were recorded during 1 or 2 24-hour periods by 206 healthy school children 7 to 15 years old. For each individual voided volumes were expressed as percentage of maximum voided volume (MVV). Mean diuresis preceding each void was estimated by dividing voided volume by voiding interval. A total of 1,098 voids were analyzed.

    Results

    The first void in the morning was the largest for a majority of the children (73%). Most daytime voids were considerably smaller than the individual MVV. Single voids less than half MVV occurred in 80% of the children, and more than one-third had voids smaller than 20% of their storage capacity. MVV was the same for children with different voiding frequency but the relative filling decreased with the number of voids per 24 hours. At high diuresis voids tended to occur at shorter intervals with somewhat larger relative filling of the bladder. Nighttime voids that occurred in 23 children were in most cases (19) much smaller than the individual MVV.

    Conclusions

    Healthy children typically void when they want to, not necessarily when they need to, and only exceptionally with a full bladder. The voiding pattern is more dependent on social activities and convenience than on physiological factors such as bladder capacity, filling and diuresis.

  • 24.
    Mizusawa, Hiroya
    et al.
    Department of Clinical Pharmacology, University of Lund.
    Hedlund, Petter
    Department of Clinical Pharmacology, University of Lund.
    Andersson, Karl-Erik
    alpha-Melanocyte stimulating hormone and oxytocin induced penile erections, and intracavernous pressure increases in the rat.2002In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 167, no 2 Part 1, p. 757-760Article in journal (Refereed)
    Abstract [en]

    PURPOSE: alpha-Melanocyte stimulating hormone (alpha-MSH; Fluka Chemie AG, Geneva, Switzerland) and oxytocin induce erection in rats after intracerebroventricular administration. We studied possible interactions of alpha-melanocyte stimulating hormone with mechanisms pertaining to oxytocin or nitric oxide.

    MATERIALS AND METHODS: We used 78 anesthetized male Sprague-Dawley rats. Catheters were implanted in the lateral cerebral ventricle or into the subarachnoid space at L6 to S1. Intracavernous pressure was documented and arterial blood pressure was directly measured.

    RESULTS: Intracerebroventricular alpha-MSH (3 microg.) produced a mean of 2.6 +/- 0.6 erectile responses (p <0.05) with a mean duration of 3.4 +/- 1.1 minutes (p <0.05). Mean peak intracavernous pressure was 114 +/- 8 cm. water. An intracerebroventricular dose of 100 microg. N-nitro-L-arginine-methyl ester HCl (Sigma Chemical Co., St. Louis, Missouri) given in intracerebroventricular fashion abolished alpha-MSH induced erectile responses, whereas intracerebroventricular administration of 500 ng. of the oxytocin receptor antagonist l-deamino, 2-D-Tyr(Oet), 4-Thr, 8-Orn-OT (Ferring AB, Malmö, Sweden) had no effect. Intracerebroventricular oxytocin (30 ng.) induced a mean of 3.2 +/- 0.9 erectile responses (p <0.05) with a mean peak intracavernous pressure of 81 +/- 8 cm. water and a mean duration of 3.3 +/- 1.1 minutes. Intrathecal alpha-MSH (3 microg.) did not produce any erectile responses, whereas a mean of 5.7 +/- 0.9 responses (p <0.001) with a mean peak intracavernous pressure of 142 +/- 8 cm. water and mean duration of 5.0 +/- 1.3 minutes was obtained with 30 ng. oxytocin intrathecally. Responses induced by intrathecal oxytocin were abolished by 100 microg. N-nitro-L-arginine-methyl ester HCl intrathecally.

    CONCLUSIONS: We confirmed by monitoring intracavernous pressure and blood pressure that supraspinal erectile responses induced by alpha-melanocyte stimulating hormone involve effects mediated by nitric oxide but are independent of oxytocinergic mechanisms. At the spinal level oxytocin produces erectile responses involving nitric oxide. alpha-Melanocyte stimulating hormone does not seem to have a spinal site of action.

  • 25.
    Mizusawa, Hiroya
    et al.
    Department of Clinical Pharmacology, University of Lund, Sweden..
    Hedlund, Petter
    Department of Clinical Pharmacology, University of Lund, Sweden.
    Brioni, Jorge D
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois, USA.
    Sullivan, James P
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois, USA.
    Andersson, Karl-Erik
    Department of Clinical Pharmacology, University of Lund, Sweden.
    Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat.2002In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 167, no 5, p. 2276-81Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Activation of soluble guanylate cyclase with a subsequent increase in intracellular levels of cyclic guanosine monophosphate is necessary for normal erection. In vascular tissue 3(5'-hydroxymethyl-2'-furyl-1-benzyl indazole (YC-1) (Abbott Laboratories, North Chicago, Illinois) has been shown to stimulate soluble guanylate cyclase independent of nitric oxide. We studied whether YC-1 modulates erectile responses in the rat.

    MATERIALS AND METHODS: The effects of YC-1 given intracavernously or intraperitoneally on intracavernous pressure were investigated in rats. Functional effects of YC-1 on neuronal and endothelial nitric oxide relaxations were studied in 3 x 10(-6) M. 1-noradrenaline contracted preparations of rat isolated corpus cavernosum.

    RESULTS: Intracavernous YC-1 (10 micromol. kg.-1) produced erectile responses with a mean intracavernous pressure plus or minus standard error of mean of 81 +/- 17 cm. water (p <0.001) and a mean duration of 7.1 +/- 3.3 minutes (p <0.001). YC-1 (10 micromol. kg.-1) given intraperitoneally also increased the amplitude and duration of erectile responses to cavernous nerve stimulation. Mean peak intracavernous pressure increased from 63 +/- 6 to 10(2) +/- 16 cm. water (p <0.05). Erections induced by a submaximal dose of 25 microg. kg.-1 apomorphine s.c. increased in number after 10 micromol. kg.-1 YC-1 intraperitoneally (p <0.05). In vitro nerve induced relaxant responses were enhanced by increasing concentrations of YC-1. Relaxations at 20 Hz. were increased from a mean of 9% +/- 5% to 52% +/- 5% at a YC-1 concentration of 10(-5) M. (p <0.001). At this concentration carbachol induced relaxations were enhanced from a mean of 19% +/- 3% to 40% +/- 9% (p <0.05).

    CONCLUSIONS: YC-1 can evoke erectile responses when given intracavernously and it enhances erections induced by cavernous nerve stimulation and apomorphine when given systemically. In vitro YC-1 enhances electrically evoked relaxations in rat corpus cavernosum. YC-1 represents an interesting pharmacological principle that may be useful for treating erectile dysfunction.

  • 26.
    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
    eRegional Oncological Center and Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Stattin, Pär
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden.
    Mommsen, Sören
    Randers Hospital, Randers, Denmark.
    Varenhors, 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.
    Prediction of Survival of Metastatic Prostate Cancer Based on Early Serial Measurements of Prostate Specific Antigen and Alkaline Phosphatase2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 1, p. 117-123Article in journal (Refereed)
    Abstract [en]

    Purpose: We determined how serial measurements of prostate specific antigen and alkaline phosphatase can be used to predict survival early in the course of hormone treated metastatic prostate cancer.

    Materials and Methods: The study was based on a prospective randomized trial of 915 patients with metastatic prostate carcinoma designed to compare parenteral estrogen (polyestradiol phosphate) vs total androgen blockade. We included 697 men who survived at least 6 months and had complete serial measurements of prostate specific antigen and alkaline phosphatase. Six models were constructed based on prostate specific antigen and alkaline phosphatase at start, and after 6 months of treatment, alkaline phosphatase flare and relative prostate specific antigen velocity. We constructed time dependent receiver operating characteristic curves with corresponding area under the curve to predict death from prostate cancer within 3 years.

    Results: The best variables to predict outcome were alkaline phosphatase at 6 months (AUC 0.79 for polyestradiol phosphate and 0.72 for total androgen blockade), alkaline phosphatase at baseline (AUC 0.70 for polyestradiol phosphate and total androgen blockade) and prostate specific antigen at 6 months (AUC 0.70 for polyestradiol phosphate and total androgen blockade). Prostate specific antigen and alkaline phosphatase levels 6 months after start of treatment give better prediction of survival than baseline levels.

    Conclusions: Alkaline phosphatase at start of treatment and alkaline phosphatase and prostate specific antigen after 6 months can be used to predict survival of hormone treated metastatic prostate cancer.

  • 27.
    Schroder, Annette
    et al.
    Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden..
    Hedlund, Petter
    Andersson, Karl-Erik
    Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden..
    Carbon monoxide relaxes the female pig urethra as effectively as nitric oxide in the presence of YC-1.2002In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 167, no 4, p. 1892-1896Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Nitric oxide (NO) and carbon monoxide (CO) have been suggested to relax smooth muscle by activating soluble guanylate cyclase (sGC), binding to the same site of the enzyme. 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) (Cayman Co., Malmö, Sweden) increases the catalytic rate of sGC by binding to an allosteric site. We investigated whether YC-1 can modulate the relaxant responses of isolated urethral smooth muscle to exogenous CO, (NO) and electrical field stimulation.

    MATERIALS AND METHODS: In spontaneously active and noradrenaline (Sigma-Aldrich Chemie GmbH, Steinheim, Germany) pre-contracted preparations of circular urethral smooth muscle from female pigs relaxant responses were evoked by electrical field stimulation before and after incubation with 10(-5) M. YC-1. The concentration-response curves for CO and NO were investigated in noradrenaline pre-contracted strips before and after incubation with YC-1. The tissue contents of cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic adenosine monophosphate after electrical field stimulation, and the administration of CO or NO was investigated in the absence and presence of YC-1.

    RESULTS: YC-1 significantly increased the amplitude of the relaxations evoked by electrical field stimulation, CO and NO, and simultaneously caused significant increases in the cGMP content in all preparations. The effect on CO induced relaxant responses was conspicuous. In the presence of YC-1 the potency and maximal relaxant effect of CO were similar to those of NO in the absence of YC-1.

    CONCLUSIONS: YC-1 enhances cGMP dependent relaxant responses of the female pig urethra in vitro. The finding that the response to CO was greatly increased after sensitizing sGC suggests a potential for CO as a relaxant mediator in urethral smooth muscle.

  • 28.
    Schröder, Annette
    et al.
    Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
    Pandita, Raj K
    Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
    Hedlund, Petter
    Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
    Warner, Margret
    Departments of Medical Nutrition and Biosciences, Karolinska Institute.
    Gustafsson, Jan-Ake
    Departments of Medical Nutrition and Biosciences, Karolinska Institute.
    Andersson, Karl-Erik
    Department of Clinical Pharmacology, University of Lund, Sweden..
    Estrogen receptor subtypes and afferent signaling in the bladder.2003In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 170, no 3, p. 1013-6Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The influence of estrogen on bladder function has been the subject of several experimental and clinical studies. In addition to the well-known estrogen receptor (ER)alpha, recently the ER subtype ERbeta was discovered. We investigated potential changes in bladder function in mice lacking either 1 or both receptor subtypes compared with WT mice.

    MATERIALS AND METHODS: Female mice lacking genes for ERalpha (ERKO), ERbeta (BERKO) or both and their WT littermates were used for the study. Continuous cystometry in awake animals was performed before and after intravesical administration of capsaicin. In addition, in vitro responses to electrical field stimulation before and after incubation with scopolamine and alpha,beta-methylene adenosine triphosphate, and to carbachol were investigated.

    RESULTS: Control cystometry revealed no significant difference in urodynamic parameters among all strains. After capsaicin instillation the micturition interval and volume decreased, and micturition pressure increased in WT, ERbeta and 2 gene mice, while no changes were seen in ERKO mice. In vitro contractility was similar in all groups. Incubation with scopolamine and alpha,beta-methylene adenosine triphosphate led to significant decreases in the response to electrical field stimulation. There was no difference in the response to carbachol among the groups.

    CONCLUSIONS: The lack of ERalpha and/or ERbeta had little effect on in vitro contractility or on continuous cystometry in awake animals. The lack of response to capsaicin instillation in ERKO suggests that ER subtypes are important for vanilloid receptor function and mechano-afferent signaling.

  • 29.
    Spetz, Anna-Clara
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Hammar, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Lindberg, Bengt
    Department of Surgery, Kungälv Hospital, Kungälv, Sweden.
    Spångberg, Anders
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Prospective evaluation of hot flashes during treatment with parenteral estrogen or complete androgen ablation for metastatic carcinoma of the prostate2001In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 166, no 2, p. 517-520Article in journal (Refereed)
    Abstract [en]

    Purpose

    We evaluated the incidence and frequency of, and distress due to hot flashes after castration therapy with polyestradiol phosphate and complete androgen ablation.

    Materials and Methods

    A total of 915 men with metastatic prostate carcinoma enrolled in the Scandinavian Prostatic Cancer Group-5 trial study were randomized to intramuscular injections of 240 mg. Polyestradiol phosphate every 2 weeks for 8 weeks followed by monthly subcutaneous injections or complete androgen ablation, that is bilateral orchiectomy or 3.75 mg. of the gonadotropin-releasing hormone analog triptorelin monthly combined with 250 mg. of the antiandrogen flutamide 3 times daily. The incidence and frequency of, and distress due to hot flashes were recorded at regular intervals using a questionnaire.

    Results

    Of the 915 men 901 were evaluated at a median followup of 18.5 months. The incidence of hot flashes was 30.1% and 74.3% in the polyestradiol phosphate and complete androgen ablation groups, respectively (p <0.001). In the polyestradiol phosphate group the frequency of and distress due to hot flashes were significantly lower than in the androgen ablation group. There was complete relief from hot flashes in 50% of the men on polyestradiol phosphate during followup compared with none on androgen ablation. The incidence of hot flashes did not differ in men with and without tumor progression.

    Conclusions

    Endocrine treatment with polyestradiol phosphate induced fewer and less distressing hot flashes than complete androgen ablation. Flashes also disappeared to a greater extent during polyestradiol phosphate than during androgen ablation. The data in this study enable us to provide thorough individual information to patients on the risk and grade of expected distress and duration of hot flashes during polyestradiol phosphate or complete androgen ablation treatment.

  • 30.
    Spetz, Anna-Clara
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Pettersson, Bill
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Hammar, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Momentary increase in plasma calcitonin gene-related peptide is involved in hot flashes in men treated with castration for carcinoma of the prostate2001In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 166, no 5, p. 1720-1723Article in journal (Refereed)
    Abstract [en]

    Purpose

    In women the vasodilatory neuropeptides calcitonin gene-related peptide and neuropeptide Y seem to be involved in menopausal hot flashes. We assessed whether plasma calcitonin gene-related peptide and neuropeptide Y change during hot flashes in men after castration.

    Materials and Methods

    We evaluated 10 men 61 to 81 years old who underwent castration due to cancer of the prostate and had frequent hot flashes for changes in plasma calcitonin gene-related peptide and neuropeptide Y during 1 day at the outpatient clinic. At least 5 blood samples were obtained between flashes and 4 were obtained during each flash. The samples were analyzed for calcitonin gene-related peptide and neuropeptide Y using radioimmunoassay technique. Hot flashes were objectively recorded by measuring peripheral skin temperature and skin conductance.

    Results

    Plasma calcitonin gene-related peptide increased 46% (95% confidence interval 21 to 71) during flashes in the 6 men in whom it was measurable. This change was statistically significant (p = 0.028). The concentration of neuropeptide Y was below the detection limit. Skin conductance and temperature increased significantly during flashes.

    Conclusions

    Calcitonin gene-related peptide is involved in the mechanisms of hot flashes in men who underwent castration due to prostate carcinoma. Thus, there may be a similar mechanism of hot flashes in women and in men deprived of sex steroids.

  • 31.
    Zeng, Jianwen
    et al.
    Jinan University, Peoples R China .
    Pan, Chuzao
    Jinan University, Peoples R China .
    Jiang, Chonghe
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Lindström, Sivert
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Cause of Residual Urine in Bladder Outlet Obstruction: An Experimental Study in the Rat2012In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 188, no 3, p. 1027-1032Article in journal (Refereed)
    Abstract [en]

    Purpose: We explored the role of bladder mechanoreceptors in post-void residual urine in rats with bladder outlet obstruction. less thanbrgreater than less thanbrgreater thanMaterials and Methods: Partial bladder outlet obstruction was induced by a urethral ligature in 11 adult female Sprague-Dawley (R) rats. Nine sham operated rats served as controls. The outcome was evaluated in acute experiments using alpha-chloralose anesthesia 6 weeks later. Bladders were catheterized for infusion, pressure recording and intravesical electrical stimulation. Bladder efferent activity was recorded from a thin pelvic nerve branch close to the bladder. Micturition contractions were triggered at different bladder volumes by a brief train of electrical stimulation of bladder afferents while monitoring post-stimulus efferent activity and reflex bladder contractions. The degree of obstruction was assessed by bladder wet weight at the end of the experiment. less thanbrgreater than less thanbrgreater thanResults: Bladder weight, micturition threshold volume, anatomical bladder capacity and peak contraction force were significantly increased in obstructed rats. In sham operated controls a triggered micturition reflex was sustained by afferent feedback from the bladder until the bladder was empty. In contrast, reflex discharges failed with substantial volume remaining in the bladder in obstructed rats. The minimal micturition reflex volume correlated positively with bladder weight, micturition threshold volume and maximal bladder capacity (r andgt;= 0.74). less thanbrgreater than less thanbrgreater thanConclusions: In rats with partial bladder outlet obstruction the micturition reflex failed before the bladder was empty due to a decreased afferent drive from bladder mechanoreceptors. Similar changes may contribute to post-void residual urine in humans with bladder outlet obstruction.

1 - 31 of 31
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf