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1.
  • Fredell, L, et al. (author)
  • Heredity of hypospadias and the significance of low birth weight
  • 2002
  • In: Journal of Urology. - 1527-3792 .- 0022-5347. ; 3, s. 1423-
  • Journal article (peer-reviewed)abstract
    • Purpose: We analyzed a large group of patients with hypospadias regarding familial aggregation, phenotype, twin rate and ethnic origin and assessed the correlation of low birth weight with hypospadias. Materials and Methods: We mailed questionnaires to 2,503 boys operated on for hypospadias in Sweden asking for additional cases of hypospadias in the family, the number of brothers in the nuclear family, and birth weight of the boys with hypospadias and their brothers. Results: Of the boys 7% reported 1 or more additional family members with hypospadias. The birth weight of the boys with hypospadias was significantly lower (p = 5 X 10(-13)) than the birth weight of their unaffected brothers. Phenotyping of 676 individuals revealed glandular hypospadias in 53%, penile forms in 39%, penoscrotal or perineal variants in 6% and cleaved prepuce as the only manifestation in 2%. There were 50% more twins than expected compared to the general population and established zygosity in 83% (67% monozygotic, 33% dizygotic). Non-Swedish ethnicity was noted in 22% of the subjects, a third of whom were from Middle Eastern countries. Conclusions: We present data on heredity, birth weight, phenotype and ethnic origin in a large group of patients with hypospadias. The finding of additional members with hypospadias in 7% of the families supports the concept that genetic factors are involved in the pathogenesis. The strong association with low birth weight may be explained by genetic and environmental factors.
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2.
  • Hang, L, et al. (author)
  • Cytokine repertoire of epithelial cells lining the human urinary tract
  • 1998
  • In: The Journal of urology. - 0022-5347. ; 159:6, s. 92-2185
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To examine the cytokine profile of epithelial cells lining the human urinary tract with the aim of differentiating between the constitutive and disease-related cytokine production in these tissues.MATERIALS AND METHODS: Sections from the renal pelvis, ureter, bladder or urethra were obtained from 22 patients undergoing urinary tract surgery and were stained with monoclonal antibodies to interleukin(IL)-1beta, IL-4, IL-6, IL-8, interferon gamma (IFNgamma) and transforming growth factor beta (TGFbeta). Sections were classified according to the presence or absence of disease in the tissue.RESULTS: Epithelial cells lining the renal pelvis, ureter, bladder or urethra all stained for IL-8 and TGFbeta (100%) in disease-free tissues and sections with cancer or interstitial cystitis (IC). In contrast, staining for IL-1beta, IL-4, IL-6 and IFNgamma varied with the disease state of the patient. Epithelial IL-1beta staining was absent (0%) in sections from healthy bladder, but positive in tissues with IC or cancer-associated pathology (50 to 100%). IL-6 staining was detected in the epithelial layer of several patients with IC or cancer related pathology, but only in cells with non-epithelial morphology and not in disease-free tissues. IFNgamma and IL-4 staining were only observed in patients with IC and only in cells with non-epithelial morphology.CONCLUSIONS: The results show that epithelial cells from all parts of the urinary tract constitutively produce IL-8 and TGFbeta and suggest that the production of other cytokines varies with the disease of the patient. Constitutive cytokine production provides the basis for a rapid host response, in the defense against mucosal attack by microbes or toxic agents.
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3.
  • Lodding, P., et al. (author)
  • Characteristics of screening detected prostate cancer in men 50 to 66 years old with 3 to 4 ng./Ml. Prostate specific antigen
  • 1998
  • In: Journal of Urology. - 0022-5347. ; 159:3, s. 899-903
  • Journal article (peer-reviewed)abstract
    • Purpose: We defined the yield and nature of prostate cancer in the setting of population based, randomized prostate specific antigen (PSA) guided screening in men with PSA levels between 3 and 4 ng./ml. who were 50 to 65 years old at the time of randomization. Materials and Methods: Sextant biopsies were performed in 243 men with PSA of 3 to 4 ng./ml. Therapy decisions were based on core cancer length, histological grade and life expectancy. Results: Of the men 32 (13.2%) had prostate cancer constituting 23% of all of the 137 prostate cancers to date detected in the first round of our screening study. Age and PSA were similar in men with and without prostate cancer. Men with prostate cancer had significantly lower free PSA and free-to-total PSA ratio, and higher PSA density. Cancer was clinical stage T1c in 27 cases and stage T2 in 5. Hypoechoic areas were noted at transrectal ultrasound in 10 cases. Digital rectal examination and transrectal ultrasound were normal in 21 cases (66%). To date 14 patients have undergone prostatectomy. Surgical specimens showed a mean tumor volume of 1.8 cc (range 0.6 to 4.4) and significant amounts of high grade tumor were present in only 3 cases. Margins were positive in 5 cases, and pathological stage was pT2 in 8 cases and pT3 in 6. Conclusions: By lowering the PSA cutoff from 4 to 3 ng./ml. an increase in cancer detection by 30% was achieved. While the addition of free-to-total ratio and PSA density may reduce the number of biopsies by about 15% with sensitivity maintained at 90%, systematic sextant biopsies were necessary in most of these men as 66% of the tumors were negative on transrectal ultrasound and digital rectal examination. The majority of these cancers were clinically significant and suitable for curative treatment. If therapy decisions are based on the pathological findings of the biopsies, the risk of treating insignificant cancers seems low.
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4.
  • Mizusawa, H, et al. (author)
  • alpha-Melanocyte stimulating hormone and oxytocin induced penile erections, and intracavernous pressure increases in the rat
  • 2002
  • In: Journal of Urology. - : Elsevier. - 1527-3792 .- 0022-5347. ; 167:2, part 1, s. 757-760
  • Journal article (peer-reviewed)abstract
    • 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 mug.) 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 mug. N-nitro-L-argininemethyl 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 1-deamino, 2-D-Tyr(Oet), 4-Thr, 8-Orn-OT (Ferring AB, Malmo, 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 mug.) 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 mug. N-nitro-L-arginine-methyl ester HCl intrathecally. Conclusions: We confirmed by monitoring intracavernous pressure and blood pressure that supraspinal erectile responses induced by a-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.
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5.
  • Mizusawa, H, et al. (author)
  • Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat.
  • 2002
  • In: Journal of Urology. - 1527-3792 .- 0022-5347. ; 167:5, s. 2276-2281
  • Journal article (peer-reviewed)abstract
    • 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.
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6.
  • Oesterling, Joseph E., et al. (author)
  • Free, Complexed and Total Serum Prostate Specific Antigen : The Establishment of Appropriate Reference Ranges for their Concentrations and Ratios
  • 1995
  • In: The Journal of urology. - 0022-5347. ; 154:3, s. 1090-1095
  • Journal article (peer-reviewed)abstract
    • Purpose: Prostate specific antigen (PSA) exists in the serum in several molecular forms that can be measured by immunodetectable assays: free PSA, PSA complexed to alpha 1-antichymotrypsin (complexed PSA) and total PSA, which represents the sum of the free and complexed forms. We determined the normal distribution of values and established the appropriate reference ranges for these 3 molecular forms of PSA and their ratios (free-to-total, complexed-to-total and free-to-complexed PSA). Knowing the amount and ratio of these molecular forms appears to be useful in enhancing the ability of PSA to distinguish potentially curable prostate cancer from benign prostatic hyperplasia and in decreasing the number of unnecessary prostate biopsies. Materials and Methods: A total of 422 healthy men 40 to 79 years old was randomly chosen from the male population of Olmsted County Minnesota and underwent a detailed clinical examination that included digital rectal examination, serum PSA determination and transrectal ultrasound to exclude the presence of prostate cancer. Using newly developed, monoclonal-monoclonal immunofluorometric assays for each molecular form, the free, complexed and total PSA, and the ratios of these 3 forms were determined for each study participant. Results: All 3 molecular forms correlated directly with patient age (r = 0.45, r = 0.43 and r = 0.45, respectively). Using the 95th percentile, the recommended age-specific reference ranges for the free, complexed and total PSA forms, respectively, are 0.5, 1.0 and 2.0 ng./ml. for men 40 to 49 years old; 0.7, 1.5 and 3.0 ng./ml. for men 50 to 59 years old; 1.0, 2.0 and 4.0 ng./ml. for men 60 to 69 years old, and 1.2, 3.0 and 5.5 ng./ml. for men 70 to 79 years old. With regard to each of the ratios (free-to-total, complexed-to-total and free-to-complexed PSA) none correlated with patient age. As a result, the appropriate upper limit of normal (95th percentile) for all 3 ratios is constant for men of all ages. These reference ranges are greater than 0.15 for free-to-total PSA ratio, less than 0.70 for complexed-to-total PSA ratio and greater than 0.25 for free-to-complexed PSA ratio. The free-to-total PSA ratio will have its greatest value for men with a serum PSA value between 2 and 10 ng./ml. Conclusions: The establishment of appropriate reference ranges for free, complexed and total PSA as well as the ratios will allow the practicing urologist to incorporate these new parameters into the diagnostic evaluation of men at risk for early, potentially curable prostate cancer.
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  • Prestigiacomo, Anthony F., et al. (author)
  • A comparison of the free fraction of serum prostate specific antigen in men with benign and cancerous prostates : The best case scenario
  • 1996
  • In: Journal of Urology. - 0022-5347. ; 156:2, s. 350-354
  • Journal article (peer-reviewed)abstract
    • Purpose: In most previous studies of free-to-total serum prostate specific antigen (PSA) ratios, the specimens from patients with prostate cancer or those with benign prostatic hyperplasia (BPH) have not been highly characterized. We compared preoperative sera from post-radical prostatectomy patients with clinically significant cancers of at least 2 cm.3 to sera from those with BPH and large, biopsy negative prostates. Materials and Methods: We used 2 different time resolved immunofluorometric assays for free and total PSA, and a combination of a chemoluminescent immunoassay for free PSA detection with an immunoradiometric assay for total PSA to measure free and total PSA. The serum ratios of free-to-total PSA in these assays were compared to those obtained previously from gel filtration studies. Sera from 51 men with prostate cancer volumes of 2 to 18 cm.3 were compared to those from 48 men with BPH and a mean prostate volume of 78 ± 7 cm.3. The respective mean serum PSA levels plus or minus standard deviation were 10.0 ± 6.3 and 8.9 ± 7.2 ng./ml. Results: Monoclonal assays for free PSA confirmed the previous study with gel filtration. For PSA 4 to 10 ng./ml., 94 to 95% of the men with prostate cancer were correctly diagnosed, with a cutoff of less than 15% for free-to-total PSA on immunofluorometric assay and less than 14% for chemoluminescent immunoassay with immunoradiometric assay. However, 46% (immunofluorometric assay) and 36% (chemoluminescent immunoassay and immunoradiometric assay) of men with BPH did not have enough free PSA for diagnosis of BPH (that is 36 to 46% false-positive rate). Conclusions: For total PSA 4 to 10 ng./ml., the sensitivity of approximately 15% free-to-total PSA for prostate cancer is high (94 to 95%) but 36 to 46% of men with BPH and a large gland will not be correctly identified. For PSA 2 to 4 ng./ml., no ratio of percent free-to-total PSA discriminated BPH from prostate cancer.
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  • Schroder, Annette, et al. (author)
  • Carbon monoxide relaxes the female pig urethra as effectively as nitric oxide in the presence of YC-1.
  • 2002
  • In: Journal of Urology. - : Elsevier. - 1527-3792 .- 0022-5347. ; 167:4, s. 1892-1896
  • Journal article (peer-reviewed)abstract
    • 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.
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9.
  • Abrahamsson, Kate, 1959, et al. (author)
  • Bladder dysfunction: an integral part of the ectopic ureterocele complex.
  • 1998
  • In: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 160:4, s. 1468-70
  • Journal article (peer-reviewed)abstract
    • We evaluate whether bladder dysfunction is common in patients with ectopic ureterocele and, if so, whether it is an integral part of the ectopic ureterocele complex or a result of surgery.From 1986 to 1995, 34 patients with a mean age of 10 months were treated for large or medium ectopic ureteroceles at our institution and 32 participated in postoperative followup. Bladder function was investigated by a careful history and repeat uroflowmetry, and residual urine estimation was assessed by ultrasound and cystometry.Of the 32 patients 19 had infrequent voiding and 3 had incontinence. Cystometric bladder capacity was increased to greater than 150% of the normal value for age in 15 of 27 patients (55%). Uroflowmetry revealed greater than 5 ml. residual urine in 15 patients (56%). Postoperatively no radiological signs of bladder neck obstruction were found. Increased bladder capacity and residual urine did not correlate with ureterocele size or location, or surgical procedure. There was no progression of bladder dysfunction with age.Children with ectopic ureterocele are at high risk for a high capacity bladder with incomplete emptying. This bladder dysfunction associated with ectopic ureterocele does not seem to be the result of surgery but an integral part of the disorder.
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  • Adolfsson, J (author)
  • Quality of life
  • 2001
  • In: The Journal of urology. - 0022-5347. ; 166:3, s. 962-963
  • Journal article (other academic/artistic)
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  • Andrén, Ove, 1963-, et al. (author)
  • How well does the Gleason score predict prostate cancer death? : A 20-year followup of a population based cohort in Sweden
  • 2006
  • In: Journal of Urology. - Baltimore : Williams and Wilkins Co.. - 0022-5347 .- 1527-3792. ; 175:4, s. 1337-1340
  • Journal article (peer-reviewed)abstract
    • Purpose Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment. Materials and Methods We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death. Results Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 – strongly correlated to Gleason score – was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%. Conclusions Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed.
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  • Gladh, Gunilla, 1943-, et al. (author)
  • Outcome of the bladder cooling test in children with neurogenic bladder dysfunction
  • 1999
  • In: Journal of Urology. - 0022-5347 .- 1527-3792. ; 161:1, s. 254-258
  • Journal article (peer-reviewed)abstract
    • PurposeWe evaluated the diagnostic use of the bladder cooling test in children with neurogenic bladder dysfunction.Materials and MethodsWe 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.ResultsThe 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.ConclusionsThe 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.
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  • Hammar, Mats, 1950-, et al. (author)
  • Acupuncture treatment of vasomotor symptoms in men with prostatic carcinoma : A pilot study
  • 1999
  • In: Journal of Urology. - 0022-5347 .- 1527-3792. ; 161:3, s. 853-856
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Hedlund, Petter, et al. (author)
  • Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase.
  • 2000
  • In: Journal of Urology. - : Elsevier. - 0022-5347 .- 1527-3792. ; 164:3 Part 1, s. 868-875
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Jahnson, Staffan, et al. (author)
  • Predictive value of p53 and pRb immunostaining in locally advanced bladder cancer treated with cystectomy
  • 1998
  • In: Journal of Urology. - Philadelphia, USA : Elsevier. - 0022-5347 .- 1527-3792. ; 160:4, s. 1291-1296
  • Journal article (peer-reviewed)abstract
    • Purpose: We elucidate the association between altered immunostaining for retinoblastoma gene protein (pRb) and p53 nuclear proteins, and cancer specific death in patients treated with cystectomy for locally advanced bladder cancer.Materials and Methods: The hospital records of 173 patients treated with cystectomy for advanced urothelial bladder cancer between 1967 and 1992 were retrospectively reviewed. Representative biopsies obtained before treatment were sectioned and stained using the standard immunohistochemical technique with antibody DO-7 (p53) and antibody PMG3-245 (pRb). A tumor was considered to have an altered p53 expression if 20% or more of tumor cells exhibited nuclear staining. Similarly, if no tumor cell had nuclear immunostaining the tumor was considered to have an altered pRb expression.Results: An altered expression was observed for p53 in 98 tumors (57%) and for pRb in 60 (35%). In a proportional hazards analysis no association was found between an altered expression of pRb or p53 and cancer specific death. This finding was also true in another analysis when the results of immunostaining for pRb and p53 were combined.Conclusions: An altered expression for pRb and/or p53 was not correlated to cancer specific death. Thus, these parameters could not be used as predictors of treatment outcome after cystectomy for locally advanced bladder cancer.
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  • Jiang, Chong-He, et al. (author)
  • Intravesical electrical stimulation induces a prolonged decrease in micturition threshold volume in the rat
  • 1996
  • In: Journal of Urology. - 0022-5347. ; 155:4, s. 1477-1481
  • Journal article (peer-reviewed)abstract
    • Purpose: Intravesical electrical stimulation (IVES) has been used clinically to treat patients with voiding disorders. The aim of the present experimental study was to obtain objective evidence of a modulation of the micturition reflex by intravesical electrical stimulation (IVES).Materials and Methods: Forty-one female rats, anesthetized by alpha-chloralose were used for the experiments. Intravesical electrical stimulation was given by a catheter electrode in the bladder (5 minutes of continuous stimulation at 20 Hz, 7 to 11 mA). The effect was evaluated by the change in cystometric micturition threshold volume.Results: The threshold volume of the micturition reflex decreased significantly to 82% of controls after IVES (p<0.001; n=31). The effect was reversible and lasted for about 1 hour. The decrease was prevented by a transient blockade of the bladder nerves during IVES.Conclusions: Intravesical electrical stimulation induced a prolonged modulation of the micturition reflex in anesthetized rats. The effect was due to activation of bladder mechanoreceptor afferents and remained long after the period of stimulation. It is proposed that the modulation was due to a prolonged enhancement of excitatory synaptic transmission in the central micturition reflex pathway. Such a modulation may underlie the curative effect of IVES in certain voiding disorders.
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  • Loskog, Angelica, et al. (author)
  • Potent antitumor effects of CD154 transduced tumor cells in experimental bladder cancer
  • 2001
  • In: Journal of Urology. - 0022-5347 .- 1527-3792. ; 166:3, s. 1093-1097
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Current intravesical immunotherapy for bladder cancer with bacillus Calmette-Guerin instillations is standard treatment for patients with high risk superficial tumors but relapses are common. We evaluated the tumor vaccine concept in murine bladder cancer by comparing tumor cell transduction with genes coding for the immunostimulatory molecules CD154, interleukin (IL)-12 and CD80 to design a novel vaccination strategy. MATERIALS AND METHODS: Adenoviral vectors were used to transduce murine bladder cancer MB-49 cells with genes coding for CD154, IL-12 and CD80. Parental or transduced MB-49 cells were injected subcutaneously into syngeneic mice. The effects of transgene expression on tumorigenicity and the generation of protective immunological memory against challenge with parental tumor were studied. RESULTS: All 76 animals injected with parental MB-49 cells had tumors within 8 to 12 days. Tumor cell expression of CD154 combined with IL-12 completely inhibited tumor outgrowth with all 21 mice tumor-free and CD154 transduction alone was almost as effective with 33 of 35 tumor-free. IL-12 production by tumor cells delayed tumor outgrowth and 4 of 10 mice remained tumor-free. Over expression of CD80 had no effect on tumorigenicity. CD154 expressing tumors were rapidly infiltrated with large numbers of CD4+ and CD8+ T cells. Mice vaccinated 4 times with adenoviral CD154 transduced MB-49 cells were completely protected against challenge with parental tumor. Co-injection of CD154 modified cells with parental MB-49 cells retarded tumor growth. CONCLUSIONS: Our experimental results suggest that the potent antitumor effects of CD154 gene transduction should be considered for immunostimulatory gene therapy for bladder cancer.
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  • Lottman, Henri B., et al. (author)
  • Long-term effects of dextranomer endoscopic injections for treatment of urinary incontinence : an update of a prospective study of 31 patients
  • 2006
  • In: Journal of Urology. - 0022-5347 .- 1527-3792. ; 175:4, s. 1485-9
  • Journal article (peer-reviewed)abstract
    • PURPOSE: A prospective study was initiated 7 years previously to assess the efficacy of endoscopic dextranomer based implants for pediatric structural incontinence. Preliminary results revealed that at 3 years 50% of the patients were either dry or significantly improved. We report long-term results in the same cohort of patients. MATERIALS AND METHODS: A total of 33 children and adolescents 5 to 18 years old with severe incontinence due to sphincteric incompetence (exstrophy-epispadias complex in 13, neuropathic bladder in 16, bilateral ectopic ureter in 4) were enrolled. Of the patients 13 underwent 2 and 4 underwent 3 treatment sessions to achieve a definitive result. Mean injected volume was 3.9 ml (range 1.6 to 12) per session. At each evaluation patients were considered cured (dryness interval 4 hours), significantly improved (minimal incontinence requiring no more than 1 pad daily and no further treatment required) or treatment failures (no significant improvement). Videourodynamics were used to study the evolution of the bladder capacity, activity and compliance. A total of 31 patients were followed 3 to 7 years after the last injection. RESULTS: At 3 years after treatment 15 of 30 patients (50%) were dry or improved. One patient who had leakage after 3 years of dryness due to bladder deterioration subsequently underwent ileocystoplasty. At 4 years 12 of 25 patients (48%) were dry or improved. At 5 years 9 of 21 patients (43%) were dry, as were 4 of 11 (36%) at 6 years and 2 of 5 (40%) at 7 years of followup. The success rate according to pathological evaluation was comparable in neuropathic bladders (7 of 14, or 50%), exstrophy (3 of 6, or 50%) and epispadias (3 of 7, or 43%). Of 12 patients who underwent bladder neck plasty before the injection of bulking agent 7 (58%) were either dry or improved. The success rate was higher in males (13 of 23, or 57%) than in females (3 of 8, or 38%). Also, at puberty 2 males who were improved became dry. Bladder capacity increased in 12 of 18 initially small bladders and remained normal and stable in 9, while 4 initially dry patients had development of recurrent leakage secondary to bladder deterioration and underwent augmentation. Otherwise, there were no long-term side effects observed related to the injection of the bulking agent. CONCLUSIONS: Endoscopic treatment of severe organic urinary incontinence with dextranomer is durable for up to 7 years of followup in 40% of the patients.
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  • Müller, Lennart, 1959, et al. (author)
  • Ultrasound assessment of detrusor thickness in children and young adults with myelomeningocele
  • 2006
  • In: J Urol. - 0022-5347. ; 175:2
  • Journal article (peer-reviewed)abstract
    • PURPOSE: We determine by ultrasonography the range of dT in carefully treated and followed children with myelomeningocele, and evaluate the role of such measurements for the understanding of bladder abnormalities in these patients. MATERIALS AND METHODS: We studied 66 children and young adults with MMC (34 males and 32 females, median age 8.1 years, range 1.1 to 20.1). Detrusor thickness was measured with a previously established ultrasonographic technique and the results were compared to those in normal children. The variation in detrusor thickness with degree of bladder dysfunction as well as with bladder wall trabeculation, kidney function and anticholinergic treatment was studied. RESULTS: The detrusor of the ventral wall was slightly thinner in children with MMC compared to normal. No significant variation in dT was found for different degrees of bladder dysfunction, bladder wall trabeculation, kidney function or anticholinergic treatment. Boys had thicker detrusor of the ventral wall than girls. CONCLUSIONS: Children with MMC, followed closely and treated according to international standards, do not acquire detrusor thickening as measured by ultrasonography. The detrusor thickness did not correlate with the degree of bladder dysfunction or renal function, or with anticholinergic treatment. Bladder wall trabeculation at VCU was not associated with bladder wall thickening on ultrasonography. We postulate that in a closely monitored and actively treated population of patients with MMC muscular hypertrophy and the development of connective tissue in the bladder wall is kept to a minimum.
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  • Spetz, Anna-Clara, 1973-, et al. (author)
  • Momentary increase in plasma calcitonin gene-related peptide is involved in hot flashes in men treated with castration for carcinoma of the prostate
  • 2001
  • In: Journal of Urology. - 0022-5347 .- 1527-3792. ; 166:5, s. 1720-1723
  • Journal article (peer-reviewed)abstract
    • PurposeIn 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 MethodsWe 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.ResultsPlasma 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.ConclusionsCalcitonin 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.
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