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1.
  • Fredell, L, et al. (författare)
  • Heredity of hypospadias and the significance of low birth weight
  • 2002
  • Ingår i: Journal of Urology. - 1527-3792 .- 0022-5347. ; 3, s. 1423-
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • Cytokine repertoire of epithelial cells lining the human urinary tract
  • 1998
  • Ingår i: The Journal of urology. - 0022-5347. ; 159:6, s. 92-2185
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • Characteristics of screening detected prostate cancer in men 50 to 66 years old with 3 to 4 ng./Ml. Prostate specific antigen
  • 1998
  • Ingår i: Journal of Urology. - 0022-5347. ; 159:3, s. 899-903
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • alpha-Melanocyte stimulating hormone and oxytocin induced penile erections, and intracavernous pressure increases in the rat
  • 2002
  • Ingår i: Journal of Urology. - : Elsevier. - 1527-3792 .- 0022-5347. ; 167:2, part 1, s. 757-760
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat.
  • 2002
  • Ingår i: Journal of Urology. - 1527-3792 .- 0022-5347. ; 167:5, s. 2276-2281
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • Free, Complexed and Total Serum Prostate Specific Antigen : The Establishment of Appropriate Reference Ranges for their Concentrations and Ratios
  • 1995
  • Ingår i: The Journal of urology. - 0022-5347. ; 154:3, s. 1090-1095
  • Tidskriftsartikel (refereegranskat)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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7.
  • Prestigiacomo, Anthony F., et al. (författare)
  • A comparison of the free fraction of serum prostate specific antigen in men with benign and cancerous prostates : The best case scenario
  • 1996
  • Ingår i: Journal of Urology. - 0022-5347. ; 156:2, s. 350-354
  • Tidskriftsartikel (refereegranskat)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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8.
  • Schroder, Annette, et al. (författare)
  • Carbon monoxide relaxes the female pig urethra as effectively as nitric oxide in the presence of YC-1.
  • 2002
  • Ingår i: Journal of Urology. - : Elsevier. - 1527-3792 .- 0022-5347. ; 167:4, s. 1892-1896
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • Bladder dysfunction: an integral part of the ectopic ureterocele complex.
  • 1998
  • Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 160:4, s. 1468-70
  • Tidskriftsartikel (refereegranskat)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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10.
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