| 1. |
- Aizawa, Naoki, et al.
(författare)
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Inhibition of Peripheral FAAH Depresses Activities of Bladder Mechanosensitive Nerve Fibers of the Rat
- 2014
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Ingår i: Journal of Urology. - : Elsevier. - 0022-5347 .- 1527-3792. ; 192:3, s. 956-963
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Austin, Paul F, et al.
(författare)
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The Standardization of Terminology of Lower Urinary Tract Function in Children and Adolescents : Update Report from the Standardization Committee of the International Children's Continence Society.
- 2014
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 191:6, s. 1863-1865
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The impact of the original International Children's Continence Society (ICCS) terminology document on lower urinary tract (LUT) function resulted in the global establishment of uniformity and clarity in the characterization of LUT function and dysfunction in children across multiple healthcare disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on pediatric LUT function.MATERIALS AND METHODS: A variety of worldwide experts from multiple disciplines within the ICCS leadership who care for children with LUT dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. Additionally, contributions and feedback from the multidisciplinary ICCS membership were solicited.RESULTS: Following a review of the literature over the last 7 years, the ICCS experts assembled a new terminology document reflecting current understanding of bladder function and LUT dysfunction in children using the resources from the literature review, expert opinion and ICCS member feedback.CONCLUSIONS: The present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of LUT function in children.
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| 3. |
- Aydogdu, Özgu, 1978, et al.
(författare)
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Near infrared spectroscopy to diagnose experimental testicular torsion: comparison with Doppler ultrasound and immunohistochemical correlation of tissue oxygenation and viability.
- 2012
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 187:2, s. 744-50
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Tidskriftsartikel (refereegranskat)abstract
- Near infrared spectroscopy measures tissue oxygenation even when there is complete cessation of blood flow. We evaluated near infrared spectroscopy to diagnose testicular torsion and blindly compared its accuracy with that of Doppler ultrasound. We also compared it by immunohistochemical evaluation of hypoxia and cell viability.Rats were randomized to 4 groups, including group 1-720-degree unilateral torsion, group 2-360-degree unilateral torsion, group 4-sham operation and group 4-720-degree unilateral torsion followed by surgical torsion reduction at minute 180. Near infrared spectroscopy and Doppler ultrasound were done blindly at minutes 0, 5, 30, 60, 180 and 400. All torsed and contralateral testicles were excised for pathological examination using hypoxia inducible factor-α for hypoxia and the TUNEL test for apoptosis. We compared all groups with the contralateral testis and the sham operated group.All blinded, near infrared spectroscopy measurements correctly identified the torsed testis after minute 5. Median oxygen saturation in groups 1 and 2 was significantly different compared to that in the sham operated group after minute 5. In group 4 near infrared spectroscopy detected detorsion with the loss of a significant oxygen saturation difference between the affected and the contralateral testicle after detorsion. At minute 400 median oxygen saturation in group 4 was not statistically different compared to that in the sham operated group (p = 0.09) but it was significantly different compared to that in groups 1 and 2 (p <0.001). In each torsed testis oxygen saturation was at least 18.75% lower than in the contralateral testis. In groups 1 and 2 hypoxia inducible factor-α staining in torsed testicles was significantly greater than that in the contralateral organ and the sham operated group. In group 4 hypoxia inducible factor-α staining after detorsion was significantly decreased compared to that in groups 1 and 2. There was no significant difference in the apoptotic index between the experimental and the contralateral testis or the sham operated group.Near infrared spectroscopy is as effective but quicker than Doppler ultrasound for detecting testicular torsion without a radiologist. Near infrared spectroscopy accurately reveals oxygen saturation, which is more vital than blood flow, on which Doppler ultrasound focuses.
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| 4. |
- Bechis, Seth K, et al.
(författare)
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Personalized medicine for the management of benign prostatic hyperplasia.
- 2014
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 192:1
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Benign prostatic hyperplasia affects more than 50% of men by age 60 years, and is the cause of millions of dollars in health care expenditure for the treatment of lower urinary tract symptoms and urinary obstruction. Despite the widespread use of medical therapy, there is no universal therapy that treats all men with symptomatic benign prostatic hyperplasia. At least 30% of patients do not respond to medical management and a subset require surgery. Significant advances have been made in understanding the natural history and development of the prostate, such as elucidating the role of the enzyme 5α-reductase type 2, and advances in genomics and biomarker discovery offer the potential for a more targeted approach to therapy. We review the current understanding of benign prostatic hyperplasia progression as well as the key genes and signaling pathways implicated in the process such as 5α-reductase. We also explore the potential of biomarker screening and gene specific therapies as tools to risk stratify patients with benign prostatic hyperplasia and identify those with symptomatic or medically resistant forms.MATERIALS AND METHODS: A PubMed® literature search of current and past peer reviewed literature on prostate development, lower urinary tract symptoms, benign prostatic hyperplasia pathogenesis, targeted therapy, biomarkers, epigenetics, 5α-reductase type 2 and personalized medicine was performed. An additional Google Scholar™ search was conducted to broaden the scope of the review. Relevant reviews and original research articles were examined, as were their cited references, and a synopsis of original data was generated with the goal of informing the practicing urologist of these advances and their implications.RESULTS: Benign prostatic hyperplasia is associated with a state of hyperplasia of the stromal and epithelial compartments, with 5α-reductase type 2 and androgen signaling having key roles in the development and maintenance of the prostate. Chronic inflammation, multiple growth factor and hormonal signaling pathways, and medical comorbidities have complex roles in prostate tissue homeostasis as well as its evolution into the clinical state of benign prostatic hyperplasia. Resistance to medical therapy with finasteride may occur through silencing of the 5α-reductase type 2 gene by DNA methylation, leading to a state in which 30% of adult prostates do not express 5α-reductase type 2. Novel biomarkers such as single nucleotide polymorphisms may be used to risk stratify patients with symptomatic benign prostatic hyperplasia and identify those at risk for progression or failure of medical therapy. Several inhibitors of the androgen receptor and other signaling pathways have recently been identified which appear to attenuate benign prostatic hyperplasia progression and may offer alternative targets for medical therapy.CONCLUSIONS: Progressive worsening of lower urinary tract symptoms and bladder outlet obstruction secondary to benign prostatic hyperplasia is the result of multiple pathways including androgen receptor signaling, proinflammatory cytokines and growth factor signals. New techniques in genomics, proteomics and epigenetics have led to the discovery of aberrant signaling pathways, novel biomarkers, DNA methylation signatures and potential gene specific targets. As personalized medicine continues to develop, the ability to risk stratify patients with symptomatic benign prostatic hyperplasia, identify those at higher risk for progression, and seek alternative therapies for those in whom conventional options are likely to fail will become the standard of targeted therapy.
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| 5. |
- Berglund, Anders, et al.
(författare)
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Comorbidity, treatment and mortality : a population based cohort study of prostate cancer in PCBaSe Sweden
- 2011
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Ingår i: Journal of Urology. - : Elsevier. - 0022-5347 .- 1527-3792. ; 185:3, s. 833-840
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Tidskriftsartikel (refereegranskat)abstract
- Purpose We examined associations among comorbidity, treatment decisions and mortality in patients with prostate cancer. Materials and Methods A total of 77,536 men diagnosed with prostate cancer between 1997 and 2006 were identified in PCBaSe Sweden from the National Prostate Cancer Register of Sweden. Logistic, Cox and competing risk regression were used to assess associations among Charlson comorbidity index, treatment and mortality. The Charlson comorbidity index was categorized into no (0), mild (1) and severe comorbidity (2+). Results In men with low risk prostate cancer 5,975 of the 13,245 (45.1%) patients without comorbidity underwent radical prostatectomy compared to 256 of the 1,399 (18.9%) men with severe comorbidity. Following adjustment for age and period of diagnosis, radical prostatectomy was less likely to be offered to men with severe comorbidity (OR 0.48, 95% CI 0.41–0.55). In men with high risk prostate cancer, radiotherapy was more common (range 7.7% to 21.3%) than radical prostatectomy (range 3.0% to 11.2%) regardless of comorbidity burden. All cause and competing cause but not prostate cancer specific mortality were increased in men with severe comorbidity (all cause HR 1.99, 95% CI 1.93–2.05; competing cause sHR 2.66, 95% CI 2.56–2.78; prostate cancer specific sHR 0.98, 95% CI 0.93–1.03). The cumulative probability of prostate cancer death given no death from competing causes was significantly higher in men with severe comorbidity in all risk groups (p <0.01). Conclusions Comorbidity affects treatment choices, and is associated with all cause, competing cause and conditional prostate cancer specific mortality. An increased conditional prostate cancer specific mortality in men with severe comorbidity may reflect less aggressive treatment, impaired tumor defense, lifestyle factors and poor general health behavior.
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| 6. |
- Brandström, Per, 1959, et al.
(författare)
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The Swedish Reflux Trial in Children: I. Study Design and Study Population Characteristics
- 2010
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 184:1, s. 274-279
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Konferensbidrag (refereegranskat)abstract
- Purpose: We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection. Materials and Methods: Children 1 to younger than 2 years with grade reflux were recruited into this prospective, open, randomized, controlled, multi-center study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercaptosuccinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle. Results: During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy. Conclusions: Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.
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| 7. |
- Brandström, Per, 1959, et al.
(författare)
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The Swedish Reflux Trial in Children: III. Urinary Tract Infection Pattern.
- 2010
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 184:1, s. 286-291
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We evaluated the difference in the febrile urinary tract infection rate in small children with dilating vesicoureteral reflux randomly allocated to 3 management alternatives, including antibiotic prophylaxis, endoscopic treatment or surveillance only as the control. MATERIALS AND METHODS: At 23 centers a total of 203 children were included in the study, including 128 girls and 75 boys 1 to younger than 2 years. Vesicoureteral reflux grade III in 126 cases and IV in 77 was detected after a febrile urinary tract infection (194) after prenatal screening (9). Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before randomization and after 2 years. The febrile urinary tract infection rate was analyzed by the intent to treat principle. RESULTS: We noted a total of 67 febrile recurrences in 42 girls and a total of 8 in 7 boys (p = 0.0001). There was a difference in the recurrence rate among treatment groups in girls with febrile infection in 8 of 43 (19%) on prophylaxis, 10 of 43 (23%) with endoscopic therapy and 24 of 42 (57%) on surveillance (p = 0.0002). In girls the recurrence rate was associated with persistent reflux after 2 years (p = 0.0095). However, reflux severity (grade III or IV) at study entry did not predict recurrence. CONCLUSIONS: In this randomized, controlled trial there was a high rate of recurrent febrile urinary tract infection in girls older than 1 year with dilating vesicoureteral reflux at study entry but not in boys. Antibiotic prophylaxis and endoscopic treatment decreased the infection rate.
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| 8. |
- Brandström, Per, 1959, et al.
(författare)
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The Swedish Reflux Trial in Children: IV. Renal Damage.
- 2010
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 184:1, s. 292-297
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We compared the development of new renal damage in small children with dilating vesicoureteral reflux randomly allocated to antibiotic prophylaxis, endoscopic treatment or surveillance as the control group. MATERIALS AND METHODS: Included in the study were 128 girls and 75 boys 1 to younger than 2 years with grade III-IV reflux. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before randomization and after 2 years. Febrile urinary tract infections were recorded during followup. Data analysis was done by the intent to treat principle. RESULTS: New renal damage in a previously unscarred area was seen in 13 girls and 2 boys. Eight of the 13 girls were on surveillance, 5 received endoscopic therapy and none were on prophylaxis (p = 0.0155). New damage was more common in children with than without febrile recurrence (11 of 49 or 22% vs 4 of 152 or 3%, p <0.0001). CONCLUSIONS: In boys the rate of new renal damage was low. It was significantly higher in girls and most common in the control surveillance group. There was also a strong association between recurrent febrile UTIs and new renal damage in girls.
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| 9. |
- Burgu, Berk, et al.
(författare)
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Lower urinary tract conditions in children with attention deficit hyperactivity disorder: correlation of symptoms based on validated scoring systems.
- 2011
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 185:2, s. 663-8
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether certain voiding problems have a higher incidence in patients with attention deficit disorder with hyperactivity compared to age matched controls.We used the Conners Parent Rating Scale-revised for attention deficit disorder with hyperactivity and lower urinary tract symptom score to evaluate voiding problems. A total of 62 children with attention deficit disorder and 124 healthy controls were enrolled. We evaluated uroflowmetry patterns in both groups. Residual urine volumes and Bristol stool scale were noted. We examined the correlation between total Conners Parent Rating Scale-revised and lower urinary tract symptom score in patients with attention deficit disorder. Additionally we analyzed each index of the Conners Parent Rating Scale-revised separately in terms of correlation with symptom subgroups for lower urinary tract symptom scores.Mean ± SD total lower urinary tract symptom score was 11.1 ± 2.9 in patients with attention deficit disorder with hyperactivity and 3.2 ± 1.3 in controls, a difference that was statistically significantly (p <0.001). With the exception of constipation, mean scores of all lower urinary tract symptom subindices were significantly higher in patients with attention deficit disorder compared to controls. Symptoms evaluated in lower urinary tract symptom score were mostly correlated with attention deficit disorder index of the Conners Parent Rating Scale-revised. If a child with attention deficit disorder has a high index in the Conners Parent Rating Scale-revised, he or she is more likely to have urgency. Also, if a child with attention deficit disorder has a high hyperactivity subscale score, he or she is more likely to have enuresis.Voiding problems are more common in children with attention deficit disorder with hyperactivity than in age matched controls. Urgency and enuresis are the outstanding problems in children with attention deficit disorder. Simultaneous use of the Conners Parent Rating Scale-revised and lower urinary tract symptom score questionnaire should be encouraged in patients with attention deficit disorder to allow a structured and quantitative evaluation of these overlapping problems.
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| 10. |
- Carlsson, Sigrid, 1982, et al.
(författare)
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Pathological Features of Lymph Node Metastasis for Predicting Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer.
- 2013
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 189:4, s. 1314-1319
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Subclassification of nodal stage may have prognostic value in men with lymph node metastasis at radical prostatectomy. We explored the role of extranodal extension, size of the largest metastatic lymph node and the largest metastasis, and lymph node density as predictors of biochemical recurrence. MATERIALS AND METHODS: We reviewed pathological material from 261 patients with node positive prostate cancer. We examined the predictive value when adding the additional pathology findings to a base model including extraprostatic extension, seminal vesicle invasion, radical prostatectomy Gleason score, prostate specific antigen and number of positive lymph nodes using the Cox proportional hazards regression and Harrell concordance index. RESULTS: The median number of lymph nodes removed was 14 (IQR 9, 20) and the median number of positive lymph nodes was 1 (IQR 1, 2). At a median followup of 4.6 years (IQR 3.2, 6.0) 155 of 261 patients experienced biochemical recurrence. The mean 5-year biochemical recurrence-free survival rate was 39% (95% CI 33-46). Median diameter of the largest metastatic lymph node was 9 mm (IQR 5, 16). On Cox regression radical prostatectomy specimen Gleason score (greater than 7 vs 7 or less), number of positive lymph nodes (3 or greater vs 1 or 2), seminal vesicle invasion and prostate specific antigen were associated with significantly increased risks of biochemical recurrence. On subset analysis metastasis size significantly improved model discrimination (base model Harrell concordance index 0.700 vs 0.655, p = 0.032). CONCLUSIONS: Our study confirms that the number of positive lymph nodes is a predictor of biochemical recurrence in men with node positive disease. The improvement in prognostic value of measuring the metastatic focus warrants further investigation.
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