OBJECTIVE: To investigate the presence of leukotriene D4 receptors in fura-2-loaded human detrusor smooth muscle cells (DSMCs) by examining the ability of leukotriene D4 to raise intracellular-free Ca2+ concentration ([Ca2+]i), to determine the origin of the leukotriene D4-mediated rise in [Ca2+]i and to investigate whether the specific leukotriene D4 receptor antagonist montelukast inhibits the Ca2+ response induced by leukotriene D4. MATERIALS AND METHODS: Detrusor muscle biopsies were obtained from patients with benign noninvasive bladder diseases undergoing cystoscopy. DSMCs were isolated using an explant technique and maintained in culture. Only primary cultures or cells passaged up to three times were used for experiments. DSMCs were characterized with immunohistochemical staining and their identity confirmed by transmission electron microscopy. [Ca2+]i was measured in single DSMCs using the Ca2+ probe fura-2 and fluorescence-ratio microscopy. RESULTS: Immunohistochemical staining showed that 80-99% of the cells were positive for smooth muscle alpha-actin. The ultrastructural features of the cultured cells were those of smooth muscle cells and showed no differentiation in a fibroblastic or myofibroblastic direction. Leukotriene D4 increased the level of [Ca2+]i in a dose-dependent manner. Calcium was mobilized almost exclusively from intracellular Ca2+ stores. There was a dose-dependent inhibition of the increase in [Ca2+]i by montelukast. CONCLUSION: The present study is the first to show the presence of specific leukotriene D4 receptors in human detrusor myocytes. This may have implications for a potential pathophysiological role of leukotriene D4 in patients with interstitial cystitis and other functional or inflammatory bladder disorders.

Calcium↗

PubMed2001

Buttock placement of the implantable pulse generator: a new implantation technique for sacral neuromodulation--a multicenter study.

OBJECTIVE: In the standard operation procedure for sacral neuromodulation, the implantable pulse generator (IPG) is implanted in a subcutaneous pocket at the lower part of the anterior abdominal wall. This procedure requires a long operation time and three incisions. With the IPG in the abdominal wall, some patients complain of displacement or pain at the IPG site postoperatively. By modifying the technique of placement of the IPG, these disadvantages are overcome. METHODS: Between August 1999 and July 2000, 39 patients underwent a buttock implant of the IPG. In 2 of these patients the position of the IPG was changed from abdominal region to the buttock. During follow-up, complications concerning the operation and location of the IPG were compared to the published literature. RESULTS: Operation time is reduced in all patients by approximately 1 h. No repositioning of the patient is required during surgery. Only a short subcutaneous tunnel is required to connect the lead to the IPG. Pain at the level of the IPG was noted in 10% of the patients, which needed no further treatment. No infections were seen and the IPG did not displace postoperatively. CONCLUSION: Buttock placement of the IPG in sacral nerve stimulation leads to shorter operation time; only two incisions are needed instead of three and a shorter subcutaneous tunnel is needed. Using this technique there are less complications and a lower re-operation rate.

Adult↗

PubMed2001

The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis.

PURPOSE: The presence of leukotriene D4 receptors in human detrusor myocytes and increased urinary leukotriene E4 in patients with interstitial cystitis and detrusor mastocytosis imply a role for cysteinyl containing leukotrienes as proinflammatory mediators in this disease. We examined the efficacy of the cysteinyl leukotriene 1 receptor antagonist montelukast for treating patients with interstitial cystitis and detrusor mastocytosis. MATERIALS AND METHODS: Ten women in whom interstitial cystitis was diagnosed according to National Institute of Diabetes and Digestive and Kidney Diseases criteria and who also had detrusor mastocytosis with a minimum of 28 mast cells per mm.2 muscle tissue were included in this study. Patients received a single dose of montelukast daily for 3 months. The efficacy of treatment was determined by 24-hour urinary frequency, nocturia and pain using visual analog scales. RESULTS: After 1 month of montelukast treatment there was a statistically significant decrease in 24-hour urinary frequency, nocturia and pain which persisted during the 3 months of treatment. After 3 months 24-hour urinary frequency had decreased from 17.4 to 12 voidings (p = 0.009), nocturia had decreased from 4.5 to 2.8 (p = 0.019) and pain had decreased from 46.8 to 19.6 mm. on a visual analog scale (p = 0.006). No side effects were observed during treatment. CONCLUSIONS: Montelukast treatment resulted in significant improvement in urinary frequency and pain. Its efficacy for decreasing urinary frequency and pain imply a role of leukotriene receptor antagonists for managing interstitial cystitis but further placebo controlled clinical studies are needed.

Acetates↗

PubMed2001

Increased urinary leukotriene E4 and eosinophil protein X excretion in patients with interstitial cystitis.

PURPOSE: The role of cysteinyl containing leukotriene C4, D4 and E4, and eosinophil protein X in interstitial cystitis is unknown. Leukotriene E4, the end product of cysteinyl containing leukotrienes, and eosinophil protein X are markers of the activation of mast cells and eosinophils, respectively. Cysteinyl containing leukotrienes are potent and specific chemoattractants for eosinophils. We compared the urinary excretion of leukotriene E4 and eosinophil protein X in patients with interstitial cystitis and in healthy controls. MATERIALS AND METHODS: Morning spot urine samples from nine patients with interstitial cystitis who fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria were collected on the day of cystoscopy with biopsies. Aliquots of urine specimens were immediately centrifuged and the supernatants were stored at -80C until use. Urine samples from 9 healthy women served as controls. Urinary leukotriene E4 and eosinophil protein X were measured by enzyme immunoassay and radioimmunoassay, respectively. All determinations were performed in duplicate and normalized to urine creatinine. RESULTS: Leukotriene E4 and eosinophil protein X were significantly increased in the morning urine of patients with interstitial cystitis compared with controls. The mean urinary excretion of leukotriene E4 plus or minus standard deviation was 148.8 +/- 62.5 and 62.2 +/- 17.5 ng./mmol. creatinine in patients and controls (p = 0.003), while the mean urinary excretion of eosinophil protein X was 109.7 +/- 70.4 and 43.7 +/- 22.0 microg./mmol. creatinine, respectively (p = 0.01). All urine cultures were negative. The mean mast cell count in detrusor biopsies in the interstitial cystitis group was 41 cells per mm.2 (range 5 to 84). Eosinophilic granulocytes were occasionally observed in the submucosa but not in the detrusor. CONCLUSIONS: Our study shows that patients with interstitial cystitis and detrusor mastocytosis have increased urinary leukotriene E4 and eosinophil protein X. It is possible that cysteinyl containing leukotrienes and eosinophil protein X are involved in the pathogenesis of interstitial cystitis. Urinary leukotriene E4 and eosinophil protein X may be useful markers for assessing the grade of activation of mast cells and eosinophils in patients with interstitial cystitis and/or for confirming the diagnosis. However, it remains to be investigated whether the increase in urinary leukotriene E4 and eosinophil protein X correlates with interstitial cystitis symptoms.

Adult↗

PubMed2000

Intra- and inter-investigator variation in the analysis of pressure-flow studies in men with lower urinary tract symptoms.

The objective of this study was to assess the intra- and inter-investigator variation in the analysis of pressure-flow studies that were performed in men with lower urinary tract symptoms. Two hospitals were involved in this study. In each hospital 100 PFS were selected. Photocopies of printouts of all PFS were analyzed manually by six experienced investigators, including determination of P(detQmax) and Q(max). Afterward, all 200 PFS were analyzed again in a different order. For each P(detQmax) and accompanying Q(max) the AG-number was calculated. With these AG numbers, the intra-investigator SD, the inter-investigator SD and the intra- and inter-investigator SD combined were calculated. The intra- and inter-investigator SD combined was 10.7. This implies that if one investigator analyzes a PFS once and determines an AG number of 40, another investigator may determine an AG number between 40 +/- 2. 77*10.7 = 10-70, using a 95% confidence interval. The inter-investigator SD was 10.0 and the intra-investigator SD was 3.7. The reproducibility of the manual analysis of urodynamic studies is moderate owing to a considerable intra- and inter- investigator variation. This is mostly caused by the substantial intra-investigator variation.

Humans↗

PubMed2000

A prospective, controlled, randomized study of the effect of a slow-release silver device on the frequency of urinary tract infection in newly catheterized patients.

OBJECTIVE: To test the effect on urinary tract infections (UTIs) in patients needing continuous indwelling catheterization, of a newly designed urine-collecting system containing an antibacterial device which slowly releases silver ions onto the inner surface of the system. PATIENTS AND METHODS: The study comprised a prospective controlled randomized trial; 213 patients fulfilled the inclusion criteria. They were randomized to a urine drainage system (comprising a Unometer 400 metering system or PP 2000N closed urine-bag system, both from Maersk Medical, Denmark) either with or without the antibacterial device. The efficacy was assessed as the number of UTIs and the time to infection in the 170 patients eligible for analysis. RESULTS: There were fewer UTIs in those using the system containing the antibacterial device (19% vs 24%), but the difference was not statistically significant (P < 0.05). CONCLUSION: The potential importance of different infection routes were highlighted, suggesting that modifications to Foley catheters and urine-collecting systems attempting to prevent UTIs should focus not only on the intraluminal pathway, but on the internal and external pathways of infection.

Adult↗

PubMed2000

Transurethral water-induced thermotherapy for the treatment of benign prostatic hyperplasia: a prospective multicenter clinical trial.

PURPOSE: We evaluate the effectiveness and safety of transurethral water-induced thermotherapy for the treatment of lower urinary tract symptoms of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 125 patients with lower urinary tract symptoms due to BPH were enrolled at 8 study centers. Pretreatment evaluation included determination of International Prostate Symptom Score (I-PSS), peak urinary flow rate and quality of life score. Patients also completed a sexual function questionnaire. Patients were evaluated 3, 6 and 12 months after water-induced thermotherapy. RESULTS: Significant improvements in I-PSS, peak urinary flow rate and quality of life score were observed as early as 3 months after water-induced thermotherapy. At 12 months I-PSS had improved by a median of 12.5 (95% confidence interval 11.5 to 13.5) versus baseline, peak urinary flow rate by 6.4 ml. per second (5.6 to 7.5) and quality of life score by 2.5 (2.0 to 2.5). I-PSS, peak urinary flow rate and quality of life score improved by 50% or more at 12 months in 61.5%, 71.3% and 71.6% of patients, respectively. No adverse impact of water-induced thermotherapy on sexual function was noted, and preexisting discomfort during ejaculation and interference in sexual function due to lower urinary tract symptoms were significantly ameliorated after treatment. Serious adverse events were infrequent and manageable. CONCLUSIONS: Water-induced thermotherapy significantly alleviates lower urinary tract symptoms of BPH, increases peak urinary flow rate and enhances patient quality of life. This novel catheter based, minimally invasive treatment is easily administered in the outpatient setting. Water-induced thermotherapy holds promise as a useful and cost-effective option for the clinical management of BPH.

Aged↗

PubMed1999

Repeated pressure-flow studies in the evaluation of bladder outlet obstruction due to benign prostatic enlargement. Finasteride Urodynamics Study Group.

Test-retest reliability of repeated voids in pressure-flow studies and the influence on maximum flow rate (Q(max)pQ), detrusor pressure at maximum flow rate (p(det)Qmax), voided volume, and residual urine were studied. Also the agreement in interpretation of pressure-flow tracings between investigators and a single blinded central reader acting as a quality control center (QCC) were assessed. In addition, correlations between p(det)Qmax and patient age, International Prostate Symptom Score (IPSS), free maximum flow rate (Qmax), and prostate volume were calculated. Using suprapubic pressure recording, 216 men with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) were investigated in 11 centers. In each pressure-flow study, three sequential voids were performed, and quality controlled recordings were analyzed for Q(max)pQ and p(det)Qmax by the QCC. Trans rectal ultrasound was used to measure the prostate volume. Mean Q(max)pQ did not change, but p(det)Qmax decreased significantly in the second and third sequential voids. Using the Abrams-Griffiths nomogram definition of obstruction, 125 patients (67%) were classified as obstructed from the first void, but only 111 patients (59%) from the third void. The agreement between the investigator assessment and that of a single blinded reader was good. There was no significant correlation between p(det)Qmax and patient age, IPSS, and Qmax, whereas a modest correlation was found between p(det)Qmax and prostate volume. In summary, there was no significant change in Q(max)pQ, but p(det)Qmax decreased for the three consecutive voids, which can be explained by a decrease in outlet resistance. The agreement between the investigator and QCC interpretations shows the value of a standardized technique, supporting the feasibility of multicenter urodynamic studies. There is a modest, but statistically significant, correlation between detrusor pressure and prostate size, supporting the hypothesis that prostate size is a contributing factor in symptomatic BPH.

Adult↗

PubMed1999

Pressure-flow studies: short-time repeatability.

The within and between examination variation in selected test parameters and test results in repeated pressure-flow studies was determined in a prospective study of consecutive pressure-flow examinations in 22 patients. The patients were pressure-flow tested twice within a month. Furthermore, it was evaluated whether there was a systematic change in the measured parameters during retesting. By using the Abrams-Griffiths nomogram, patients were classified as obstructed, equivocal, or unobstructed. Within and between examination variations in classification were evaluated. We found a systematic variation in P(det.Qmax) during testing, which in the absence of statistically significant systematic variations in P(det.Close) and Qmax, indicates a physiological effect of repeated pressure-flow studies, resulting in a less-obstructed second voiding. Supporting this, we found that all patients who changed group of classification of bladder outlet obstruction in the first examination shifted to a group of less obstruction, as did 66% of the patients who changed group of classification of bladder outlet obstruction in the second examination. Still, 80, respectively 85%, of the patients remained in the same group of classification of bladder outlet obstruction during retesting in the first and second examinations, respectively. Classifying the degree of bladder outlet obstruction by Qmax, P(det.Qmax), and P(det.Close) 85% of the patients reproduced their test results accurately in both examinations and taking only the first voiding in both examinations into account 95% reproduced their test results.

Aged↗

PubMed1999

Continued improvement in pressure-flow parameters in men receiving finasteride for 2 years. Finasteride Urodynamics Study Group.

OBJECTIVES: To assess the long-term effects of finasteride on pressure-flow parameters in men with urodynamically documented bladder outflow obstruction (BOO). METHODS: One hundred twenty-one men with benign prostatic enlargement (BPE) and lower urinary tract symptoms (LUTS) underwent a pressure-flow study (PFS) at 1 of 11 clinical centers. The PFS technique was standardized, and all tracings were read by a single reader unaware of the treatment group. Patients who were obstructed according to a modified Abrams-Griffiths nomogram were randomized to 5 mg finasteride (n = 81) or placebo (n = 40) for 12 months; all patients continuing into an open extension received finasteride during the second 12 months of therapy. Results of the initial 12-month study demonstrated the benefit of finasteride treatment on PFS parameters. To examine the continuing effects over time, an analysis of the data from 54 patients who completed 24 months of treatment with finasteride is provided. RESULTS: Detrusor pressure at maximum flow (PdetQmax) continued to decrease during the second 12 months of therapy (decreases of 5.3 and 11.7 cm H2O at months 12 and 24, respectively). The percentage of patients obstructed by Abrams-Griffiths classification decreased from 76.2% at baseline to 66.7% at month 12 and 59.6% at month 24. An intention-to-treat analysis yielded similar results. CONCLUSIONS: Finasteride improves urodynamic measures of obstruction in men with BPE and LUTS, with continued improvement during the second 12 months of therapy.

Double-Blind Method↗

PubMed1999

The responsiveness of the ICSmale questionnaire to outcome: evidence from the ICS-'BPH' study.

OBJECTIVE: To evaluate the responsiveness of the ICSmale questionnaire to the outcome of treatments for lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Consecutive men aged >45 years attending 23 urology centres in 12 countries, with symptoms suggestive of bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), were recruited to Phase I of the International Continence Society (ICS)-'BPH' study. In Phase II of the ICS-'BPH' study, 355 men in 15 centres in nine countries were followed up, having proceeded to treatment according to clinical practice. All men completed the ICS-'BPH' study questionnaire at baseline and follow-up, including the ICSmale which concerns LUTS and related problems. RESULTS: Patients included in Phase II were similar to those in Phase I according to age and levels of baseline symptoms. Patients received a range of treatments: 32% TURP, 29% drug therapies, 20% watchful waiting, 9% minimally invasive therapies and 10% 'others' (including open prostatectomy). For patients who underwent TURP, most LUTS, including voiding and filling symptoms, were highly statistically significantly better at follow-up than at baseline (P<0.0001). For drug, minimally invasive and 'other' treatments, fewer LUTS were highly statistically significantly better. For those undergoing watchful waiting, no symptoms were significantly different between baseline and follow-up. CONCLUSION: The ICSmale questionnaire, in addition to being psychometrically valid and reliable, is responsive to change in outcome.

Age Factors↗