bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of microsurgical varicocelectomy on serum follicle stimulating hormone, testosterone and free testosterone levels in infertile men with varicocele
Authors: Cayan  , Kadioglu  , Orhan  , Kandirali  , Tefekli  , Tellaloglu
Published: March 2003

Objectives

To analyse the effects of varicocelectomy on serum follicle‐stimulating hormone (FSH), testosterone and free testosterone levels, and to investigate the interrelationships between seminal and hormonal variables.

Patients and methods

The records were retrospectively evaluated for 78 infertile patients who underwent microsurgical inguinal varicocelectomy, with documented serum FSH, testosterone, free testosterone levels, sperm concentration and sperm motility before and after surgery. Left and bilateral varicoceles were detected in 40 and 38 patients, respectively. In addition, serum hormonal values of 10 fertile men in whom physical examinations and Doppler ultrasonography revealed no evidence of varicocele were recorded and used as a control group.

Results

The mean (sd) serum FSH levels of all patients decreased from 15.21 (3.34) before surgery to 10.82 (2.93) mIU/mL afterward (P=0.01), and serum testosterone levels increased from 5.63 (1.40) to 8.37 (2.2) ng/mL (P=0.01), whereas free testosterone levels increased from 23.13 (3.19) to 32.83 (4.37) pg/mL (P<0.001). In contrast to the significant difference in sperm motility before and after surgery of all patients (P<0.01), the difference in sperm count was insignificant (P>0.05). Thirty‐six patients with high serum FSH levels before surgery had significantly lower levels afterward (P=0.001). In this group, the sperm concentration and motility also increased, from 17.66 (4.35) to 20.76 (4.37) million/mL (P=0.05) and from 30.9 (4.4)% to 37.5 (4.34)%, respectively (P=0.01). In the remaining 42 patients who had normal preoperative serum FSH levels, there was a slight decrease after surgery (P=0.02). Their sperm concentration increased slightly (P=0.04), and motility also increased (P=0.001). Sixty patients had a significantly higher testosterone level after surgery; in this group the sperm concentration and motility increased (P=0.01).

Conclusion

Varicocelectomy promotes Sertoli and Leydig cell function. The significant increase in serum free testosterone level results in a significant improvement in sperm concentration and motility.
Focal changes in nerve, muscle and connective tissue in normal and unstable human bladder
Authors: Charlton  , Morley  , Chambers  , Gillespie
Published: March 2003

Objective

To compare and quantify, in a morphological study, the changes that occur in the connective tissue elements (elastin and collagen), muscle fibre diameters and nerve densities between normal, idiopathic and neuropathic bladders.

Materials and methods

Bladder tissue was obtained from 27 patients undergoing cystectomy for carcinoma, from 12 with idiopathic instability and from seven neuropathic patients who were undergoing ileocystoplasty. A combination of histochemical and immunohistochemical techniques were used to detect detrusor muscle, connective tissue and nerve profiles in the bladder tissue.

Results

In both idiopathic and neuropathic bladder tissue the structural changes were highly punctate. From the density of nerve profiles, three areas were defined: (i) apparently unaffected normal fascicles with a high density of nerves, no hypertrophy of the muscle and no infiltration of elastin and collagen. The nerve density in these areas was similar to that in normal bladder tissue. (ii) Fascicles with a low density of nerve profiles, muscle hypertrophy but no connective tissue infiltration. (iii) Areas with few nerve profiles, muscle hypertrophy and extensive elastin and collagen infiltration within the fascicles. The mean (sem) density of nerve profiles in control tissue was 752 (53) nerves/mm2 and in the idiopathic bladders was 905 (91), 81 (20) and 74 (38) nerves/mm2 in the three defined areas, respectively. In the neuropathic tissues the nerve profile densities were 672 (249), 57 (23) and 37 (28) nerves/mm2 , respectively. Fibre diameter, elastin and collagen content and nerve density were measured in normal and unstable bladder tissue using these three defined areas. The mean (sem) fibre diameter was 6.81 (0.52) in normal bladder; in idiopathic bladder tissue the fibre diameters in the three areas were 6.72 (0.62), 7.06 (0.62) and 7.34 (1.15) μm, respectively, and in neuropathic bladders were 6.75 (0.62), 8.24 (0.62) and 9.35 (0.62) μm, respectively. The relative areas of elastin were 0.79 (0.70), 0.56 (0.45) and 18.3 (4.1)% for the control, normal and affected areas of the neuropathic bladders, respectively, and the relative areas of collagen were 3.5 (1.3), 6.15 (3.6) and 15.7 (5.0)%, respectively. The pattern was similar in idiopathic bladders.

Conclusion

These observations suggest that the primary defect in the idiopathic and neuropathic bladders is a loss of nerves accompanied by a hypertrophy of the cells. These changes may continue with further hypertrophy of the cells and an increased production of elastin and collagen within the muscle fascicles.
A comparison of ambulatory and conventional urodynamic studies in men with borderline outlet obstruction
Authors: Rosario  , Macdiarmid  , Radley  , Chapple
Published: March 2003

Objective

To compare detrusor function and outlet behaviour on ambulatory urodynamic monitoring (AUM) with conventional cystometrography in symptomatic men with borderline evidence of bladder outlet obstruction (BOO), as determined by conventional cystometrography, and to assess the usefulness of AUM in reclassifying this population of patients into obstructed and unobstructed groups.

Patients and methods

Sixty‐nine consecutive men (mean age 59.6 years) with lower urinary tract symptoms (mean International Prostate Symptom Score 19.1) and borderline BOO on a medium‐fill conventional urodynamic study (CUS) were examined prospectively with AUM. Detrusor contractility, obstruction grade, maximal voiding detrusor pressure (pdetmax), detrusor pressure at peak flow (pdet Qmax) and peak flow rate (Qmax ) determined by both methods were compared. The incidence of detrusor instability (DI) detected by both modalities was also evaluated.

Results

There was considerable disagreement between the investigations during the voiding phase. Detrusor contractility was higher on AUM than on CUS (P=0.003) and obstruction grade was significantly lower on AUM (P=0.018). There was no difference in pdetmax nor pdet Qmax . The mean (95% confidence interval) Qmax was higher on AUM, at 12.9 (1.3) mL/s, than on CUS, at 8.9 (0.8) mL/s. On the Abrams‐Griffiths nomogram the most significant changes were six men (10%) from equivocal to obstructed, seven (11%) from equivocal to unobstructed and two (3%) from obstructed to unobstructed on CUS and on AUM, respectively. Thus, in 24% of patients there was a potentially clinically significant change resulting from the information generated by AUM. DI was identified on CUS in 26 (41%) men and on AUM in 25 (40%); 35 men (56%) had evidence of DI on either AUM or CUS.

Conclusion

The significant disagreement between the findings on CUS and AUM suggests that the conditions under which pressure‐flow investigations are carried out significantly affect findings in borderline cases. The reclassification of patients by AUM into obstructed and unobstructed groups occurs in 24% and may be clinically relevant. AUM appears to be complementary to CUS in the assessment of men who are borderline for obstruction on conventional testing, but the clinical implications of this have yet to be determined.
The responsiveness of the ICSmale questionnaire to outcome: evidence from the ICS‐‘BPH’ study
Authors: Donovan  , Brookes  , De La Rosette  , Peters  , Porru  , Kondo  , Dabhoiwala  , Millard  , Bosch  , Nordling  , Matos Ferreira  , Höfner  , Mostafid  , Walter  , Nissenkorn  , Frimodt Moller  , Mendes Silva  , Chapple  , Abrams
Published: March 2003

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.
The effects of experimental varicocele on testicular histology and fertility in monorchic adult rats
Authors: Asci  , Sarikaya  , Büyükalpelli  , Yilmaz  , Yildiz
Published: March 2003

Objective

To determine the effects of a left‐sided experimental varicocele on testicular morphology and fertility in right hemicastrated adult rats.

Materials and methods

A double‐controlled experimental study was carried out using mature Sprague‐Dawley rats, with 12 rats in each treated group and five corresponding controls. Group 1 underwent right orchidectomy, group 2 right orchidectomy and a left varicocele, and group 3 only a left varicocele; each control group underwent a corresponding sham operation. Two months after surgery each rat was placed with two mature female rats for one month to assess fertility. All the rats were then killed and their testes weighed; the mean testicular weight was calculated for each group and the mean seminiferous tubule diameter (STD) measured. Johnsen scores and histological abnormalities were evaluated for each testis using light microscopy.

Results

The mean (sem) testicular weight and STD in group 2 were significantly lower, at 1311 (100) mg and 225 (11) μm, respectively, than in group 1, at 1771 (28) mg and 255 (4) μm (P<0.05). The mean weights of both testes in rats in group 3 were significantly lower than those in group 1 (P<0.05) and although both mean STDs were less than in group 1, the differences were not significant (P>0.05). There were no differences between the Johnsen scores in groups 2 and 3. There were severe histological abnormalities in the left testes in three of nine and two of eight animals in group 2 and 3, respectively; in group 3, changes in the right testis were detected in one rat. Six of nine and seven of eight rats were fertile in group 2 and 3, respectively.

Conclusion

Experimental left varicocele decreased the left testicular weight and STD in both hemicastrated and intact adult rats. However, the presence of the right testis is important for preserving fertility.
The effects of long‐term oral administration of l‐arginine on the erectile response of rabbits with alloxan‐induced diabetes
Authors: Yildirim  , Ayan  , Sarioglu  , Gültekin  , Bütüner
Published: March 2003

Objective

To investigate the effects of the long‐term oral administration of l‐arginine on the impaired neurogenic and endothelium‐dependent relaxation responses of corpus cavernosum smooth muscle from alloxan‐induced diabetic rabbits.

Materials and methods

Thirty‐two New Zealand white rabbits were used in four groups of eight each. In group 1, the rabbits received no treatment after the induction of diabetes with alloxan hydrochloride given intravenously; in group 2, l‐arginine (1 mg/mL) was administered orally after the induction of diabetes; in group 3, 6 U/day of insulin was injected subcutaneously; group 4 was maintained with no treatment (as litter‐mate controls) for 8 weeks. Thereafter, the rabbits were killed by exsanguination and the penis removeden bloc. The reactivity of corpus cavernosum strips from the penis was then assessed in organ chambers.

Results

Relaxation and contraction responses of corpus cavernosum strips to sodium nitroprusside and potassium chloride, respectively, were similar in all groups. Relaxation responses of corpus cavernosum strips elicited by electrical field stimulation and carbachol from rabbits in group 1 were less than in controls; the responses to carbachol were not significantly impaired in group 2 and 3, whereas responses to electrical field stimulation were impaired in both groups when compared with the control group.

Conclusion

The impairment of endothelium‐dependent and nerve‐mediated relaxation by diabetes appears to involve an alteration in nitric oxide/cyclic GMP pathway. Administration of oral l‐arginine increased endothelium‐dependent relaxation, probably through activating nitric oxide synthase. Additionally, decreasing elevated blood glucose concentration and advanced glycosylation products by insulin treatment protected endothelium‐dependent relaxation, whereas neither l‐arginine nor insulin treatment restored impaired neurogenic relaxation.
Effects of ethanol and its metabolite acetaldehyde on responses of the rat bladder
Authors: Kim  , Moon  , Sohng  , Lee  , Lee  , Lee
Published: March 2003

Objective

To investigate the pharmacological effects of ethanol and its metabolite acetaldehyde on isolated rat bladder muscle, and thus assess the potential influence of ethanol ingestion on the risk of urinary retention in patients with benign prostatic hyperplasia.

Materials and methods

Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a pressure transducer. The acute or prolonged effects of ethanol (1–4%) or acetaldehyde (0.01, 0.1 or 1 mmol/L) were assessed on resting tension, electrical field stimulation (EFS), and bethanechol‐ (0.5 mmol/L), ATP‐ (2 mmol/L) or KCl‐ (127 mmol/L) induced contraction. To determine the mechanism of acetaldehyde‐induced stimulation, an antihistamine, diphenhydramine was used after bethanechol stimulation.

Results

At the concentrations used, ethanol and acetaldehyde did not change the pH of the bathing medium. The resting tension of the muscle was not changed by ethanol, and acetaldehyde caused only a small increase in baseline tone at 1 mmol/L. Incubation with ethanol or acetaldehyde significantly suppressed contractility induced by EFS, bethanechol, ATP or KCl at each concentration (P<0.05). Contractions induced by all drugs were not changed significantly by the acute application of ethanol and the acute application of acetaldehyde did not affect contractions induced by ATP or KCl. However, EFS‐ or bethanechol‐induced contractions were significantly enhanced (P<0.05). The acetaldehyde‐induced effects were completely blocked by the H1 antagonist, diphenhydramine (10 μmol/L).

Conclusions

Ethanol did not affect resting tension but acetaldehyde and ethanol suppressed bladder muscle contractions. However, direct acetaldehyde‐stimulation may release histamine and enhance contractility. This suggests that chronic alcoholism rather than acute intoxication is more likely to provoke urinary retention.
The histological extent of the local spread of carcinoma of the penis and its therapeutic implications
Authors: Agrawal A. , Pai D. , Ananthakrishnan N. , Smile S.R. , Ratnakar C.
Published: March 2003

Objective To explore the possibility of reducing the margin of clearance at surgery for carcinoma of the penis without causing an increase in the incidence of local tumour recurrence, so that the functional and cosmetic compromise associated with penectomy might be minimized.

Patients and methods Sixty‐four patients underwent partial or total penectomy based on the extent of tumour. The specimens were evaluated histologically for grade and for proximal microscopic extensions beyond the grossly visible tumour margin, by examining serial proximal 5 mm sections. The histological grade of the lesion was correlated with its clinical site, morphology and proximal microscopic spread. Differences were assessed using the chi‐squared test.

Results Of 64 tumours, 31% were grade 1, 50% grade 2 and the remaining 19% grade 3. Higher grade lesions were more likely to involve the penile shaft. The maximum proximal histological extent was 5 mm for grades 1 and 2, and 10 mm for grade 3 tumours; there was no discontinuous spread.

Conclusions Histological grading is mandatory in the management of carcinoma of the penis. A 10‐mm clearance is adequate for grade 1 and 2 lesions, and 15 mm for grade 3 tumours. This approach would qualify more patients for partial rather than total amputation; the residual length of the penis would then be cosmetically and functionally more acceptable.
A pilot study of a bioabsorbable self‐reinforced poly L‐lactic acid urethral stent combined with finasteride in the treatment of acute urinary retention from benign prostatic enlargement
Authors: Isotalo T. , Talja M. , Välimaa T. , Törmälä P. , Tammela T.L.J.
Published: March 2003

ObjectiveTo assess whether patients with acute urinary retention from benign prostatic enlargement can be treated with a combined therapy comprising a bioabsorbable self‐reinforced poly L‐lactic acid (SR‐PLLA) urethral stent and finasteride.

Patients and methodsEleven men in acute urinary retention were treated as outpatients; they had a suprapubic catheter inserted and the SR‐PLLA stent placed cystoscopically. The patients were allowed to attempt to void spontaneously after 2 days.

ResultsAll patients started to void spontaneously within 2 weeks. There was a steady improvement in urinary flow rates up to 9 months, followed by a slight impairment after the bioabsorption of the stent. During the mean (range) follow‐up of 24 (23–26) months only three patients required surgical treatment.

ConclusionThe bioabsorbable SR‐PLLA stent combined with finasteride therapy provides a promising new alternative in the treatment of acute urinary retention, especially in patients unfit for surgical therapy. Larger, placebo‐controlled studies are needed to establish the efficacy of this combined therapy.
Conservative treatment of urge urinary incontinence in women: a systematic review of randomized clinical trials
Authors: Berghmans L.C.M. , Hendriks H.J.M. , De Bie R.A. , Van Waalwijk E.S.C. , Van Doorn  , Bø K. , Van Kerrebroeck PH.E.V.
Published: March 2003

Objective To assess the efficacy of physical therapies for first‐line use in the treatment of urge urinary incontinence (UUI) in women, using a systematic review of randomized clinical trials (RCTs).

Materials and methods A computer‐aided and manual search was carried out for RCTs published between 1980 and 1999 investigating the treatment of UUI defined by the keywords ‘physical therapies’, e.g. bladder (re)training (including ‘behavioural’ treatment), pelvic floor muscle (PFM) exercises, with or without biofeedback and/or electrical stimulation. The methodological quality of the included trials was assessed using methodological criteria, based on generally accepted principles of interventional research.

Results Fifteen RCTs were identified; the methodological quality of the studies was moderate, with a median (range) score of 6 (3–8.5) (maximum possible 10). Eight RCTs were considered of sufficient quality, i.e. an internal validity score of  5.5 points on a scale of 0–10, and were included in a further analysis. Based on levels‐of‐evidence criteria, there is weak evidence to suggest that bladder (re)training is more effective than no treatment (controls), and that bladder (re)training is better than drug therapy. Stimulation types and parameters in the studies of electrical stimulation were heterogeneous. There is insufficient evidence that electrical stimulation is more effective than sham electrical simulation. To date there are too few studies to evaluate effects of PFM exercise with or without biofeedback, and of toilet training for women with UUI.

Conclusion Although almost all studies included reported positive results in favour of physical therapies for the treatment of UUI, more research of high methodological quality is required to evaluate the effects of each method in the range of physical therapies.
Telomerase activity as a potential marker in preneoplastic bladder lesions
Authors: Lancelin F. , Anidjar M. , Villette J.‐M. , Soliman A. , Teillac P. , Le Duc A. , Fiet J. , Cussenot O.
Published: March 2003

Objective To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis.

Patients and methods Tissue telomerase activity was assayed by two different techniques, the telomeric repeat amplification protocol‐polymerase chain reaction (TRAP‐PCR) and a telomerase PCR‐enzyme linked immunosorbent assay. Malignant and inflammatory bladder lesions and their adjacent normal tissues were assessed for telomerase activity in a group of 18 patients, 14 of whom had urothelial carcinoma and four a nonspecific inflammatory lesion of the bladder.

Results Eleven of the 14 tumour samples analysed were telomerase‐positive and two of the three telomerase‐negative tumour samples had a detectable ‘telomerase inhibitor’. In the apparently normal tissues next to bladder tumours, four of the 14 specimens were telomerase‐positive. Interestingly, these lesions were always next to high‐grade muscle‐invasive bladder tumours (pT2G3). Two of the four nonspecific inflammatory lesions (one of cystitis glandularis and one of severe dysplasia), known to be preneoplastic lesions, were also telomerase‐positive.

Conclusion These results strongly suggest that the reactivation of telomerase may be an early event in bladder carcinogenesis, preceding morphological changes related to malignant transformation. Telomerase activity may therefore be useful both as an indicator of malignant potential in preneoplastic lesions, e.g. cystitis glandularis and severe dysplasia, and as a prognostic marker of bladder tumour relapse or progression.
Surveillance for bladder cancer: the management of 4.8 million people
Authors: Wright M.P.J. , Jones D.J.
Published: March 2003

Objective To document the workload of bladder cancer surveillance on the British urologist.

Methods Thirty‐one consultant urologists serving a population of 4.8 million were sent postal questionnaires eliciting their views on the management of superficial bladder cancer. The number, type and outcome of cystoscopies performed over a 6‐week period throughout the region was then assessed prospectively.

Results One person in 1450 in the South‐west region is undergoing follow‐up for bladder cancer. Of the responding consultants, 36% would give a single dose of intravesical chemotherapy within 24 h of resection for a G1/2 pTa tumour and 84% would perform the first check cystoscopy at 3–4 months. Over the 6‐week period of the study, 696 cystoscopies were performed; there was considerable variation among centres in the choice of cystoscopy type, with 3–80% being rigid cystoscopies. Overall, there was a positive finding in 31% of the assessments.

Conclusion This study documents the practice of a significant number of UK urologists in the management of superficial bladder cancer. There are considerable variations among individuals in the type and timing of check cystoscopy.
A 10‐year follow‐up after Kegel pelvic floor muscle exercises for genuine stress incontinence
Authors: Cammu H. , Van Nylen M. , Amy J.J.
Published: March 2003

Objective To determine the outcome 10 years after an individual course of pelvic floor muscle (PFM) exercises for genuine stress incontinence.

Patients and methods Postal questionnaires were sent to 52 women who had undergone PFM training 10 years earlier, and their medical files were reviewed. The main outcome measures were the patients’ self‐assessment of therapy outcome, the frequency of PFM exercises at home, and the demand for surgery after physiotherapy.

Results Forty‐five women (87%; mean age 61 years) were suitable for analysis. On completing the course of PFM exercises, physiotherapy had been apparently successful in 24 (53%), and considered to have failed in 21 women (47%). Sixteen of the 24 successful patients remained satisfied with their urinary continence when reassessed 10 years later; two women had undergone surgery (8%). In the group where physiotherapy initially failed, five women (24%) who had not had surgery claimed to be much improved; 13 women (62%) had undergone surgery. Overall, women in whom the conservative treatment of stress incontinence had produced an improvement over the 10 years had practised PFM exercises more regularly (76%) than the others (55%; not significant). However, an active voluntary PFM contraction before a sudden intra‐abdominal pressure rise (‘perineal lock’) appeared to be responsible for most of the success.

Conclusions When PFM training is initially successful, there is a 66% chance that the favourable results will persist for at least 10 years.
The protective effects of nitric oxide on the contralateral testis in prepubertal rats with unilateral testicular torsion
Authors: Dokucu A.I. , Öztürk H. , ÖzdemiR E. , Ketani A. , Büyükbayram H. , Yücesan S.
Published: March 2003

Objective To investigate histological changes in the contralateral testis of rats with unilateral testicular torsion and the protective effects of nitric oxide (NO) on possible damage.

Material and methods Twenty‐eight prepubertal male Sprague‐Dawley rats were divided into four equal groups. Group 1 underwent a sham operation of the right testis under general anaesthesia. Group 2 underwent a similar operation but the right testis was rotated 720° clockwise for 6 h, maintained by fixing the testis to the scrotum, and saline infused during the procedure. Group 3 underwent similar torsion but
l‐arginine methyl ester (a precursor of NO) was infused during the procedure. In Group 4, NG‐nitro‐l‐arginine‐methyl ester, a NO synthase inhibitor, was infused separately during the administration of
l‐arginine methyl ester and torsion. All the left (untwisted) testes were removed from rats 21 days after surgery and evaluated histologically, assessing seminiferous tubule diameter, loss of sperm and spermatids, loss of germ cell layers, disarray of germ cell layers, rupture of tubules, Leydig cell proliferation and reaction in the ruptured tubules, and oedema.

Results There was a significant difference in the indicators of histological damage between groups 2 and 4 and groups 1 and 3, except for the Leydig cell reaction in the ruptured tubules and oedema. The damage was significantly less in group 3 than in groups 2 and 4.

Conclusion These results suggest that long‐term histopathological changes in the contralateral testes are important after unilateral testicular torsion and that NO has a protective effect on the contralateral testis.
Role of C‐afferent fibres in the mechanism of action of sacral nerve root neuromodulation in chronic spinal cord injury
Authors: Shaker H. , Wang Y. , Loung D. , Balbaa L. , Fehlings M.G. , Hassouna M.M.
Published: March 2003

Objective  To determine whether sacral root neuro‐modulation (a promising therapeutic modality in patients with refractory voiding and storage problems) has its effect through the blockade of C‐afferent fibres that form the afferent limb of a pathological reflex arc responsible for the dysfunction of bladder storage.

Materials and methods  The study comprised 39 female Sprague Dawley rats divided into three equal groups: normal controls (group 1); spinally transected at T10 (group 2); spinally transected and electrically stimulated bilaterally at S1 for 6 h daily (group 3). Three weeks after transection the rats were assessed using urodynamics; substance P, neurokinin A and calcitonin gene‐related peptide (CGRP) were extracted from the dorsal root ganglia (DRG) of the L5 and L6 roots and quantified by radioimmunoassay.

Results  Spinally transected rats developed urinary bladder hyper‐reflexia after 3 weeks. This was associated with a significant increase in the neuropeptide content of the DRG of L6. Electrostimulation of S1 significantly decreased the neuropeptide content of L6. In contrast, transection and S1 neurostimulation did not affect the neuropeptide content of the L5 DRG, except for CGRP, which increased after spinal transection and decreased with neurostimulation.

Conclusions  In spinally transected rats, sacral root neurostimulation abolished bladder hyper‐reflexia and attenuated the rise in neuropeptide content of the L6 DRG. These results suggest that the blockade of C‐afferent fibre activity is one of the mechanisms of action of sacral root neuromodulation.
Efficacy of trospium chloride in patients with detrusor instability: a placebo‐controlled, randomized, double‐blind, multicentre clinical trial
Authors: Cardozo L. , Chapple C.R. , Toozs‐hobson P. , Grosse‐freese M. , Bulitta M. , Lehmacher W. , Strösser W. , Ballering‐brühl B. , Schäfer M.
Published: March 2003

Objectives To assess the efficacy and safety of trospium chloride (TCl, 20 mg twice daily) in the treatment of detrusor instability, compared with placebo.

Patients and methods In all, 208 patients were allocated at random to either TCl or placebo in a double‐blind clinical study; the patients were treated for 3 weeks. Urodynamic values were measured at the beginning and end of the treatment period. Adverse events were recorded on patient diary cards. A confirmatory adaptive procedure with one planned interim analysis was used to evaluate efficacy.

Results Trospium chloride produced significant improvements in maximum cystometric bladder capacity (median treatment effect 22.0 mL, mean 37.3 mL, one‐sided P = 0.0054) and urinary volume at first unstable contraction (median treatment effect 45.0 mL, mean 63.6 mL, one‐sided P = 0.0015). The patients’ assessment of efficacy showed significantly greater clinical improvement in the TCl group than in the placebo group (two‐sided P = 0.0047). Furthermore, TCl was well tolerated, with similar frequencies of adverse events reported in both groups (68% in the TCl and 62% in the placebo group).

Conclusion Trospium chloride (20 mg twice daily) is an effective and safe option for the treatment of detrusor instability.
The significance of the free‐to‐complexed prostate‐specific antigen (PSA) ratio in prostate cancer detection in patients with a PSA level of 4.1–10.0 ng/mL
Authors: Okegawa T. , Kinjo M. , Watanabe K. , Noda H. , Kato M. , Miyata A. , Murata A. , Yoshii M. , Nutahara K. , Higashihara E.
Published: March 2003

Objective To compare the ratio of free prostate specific antigen (fPSA), total PSA (tPSA) and complexed PSA (cPSA, measured using a novel immunoassay) with other variables used to detect prostate cancer in patients with intermediate serum PSA levels of 4.1–10.0 ng/mL.

Patients and methods 

From July 1997 to August 1998, 140 consecutive patients were assessed; all had intermediate serum PSA levels and/or abnormal findings on a digital rectal examination. All patients underwent transrectal ultrasonography (TRUS)‐guided biopsy, and the prostate and transition zone volumes were determined by TRUS. Free and tPSA were measured using the Tandem‐R assay (Hybritech Corp., San Diego, CA). PSA complexed with α1‐antichymotrypsin (cPSA) was measured using an appropriate assay. The ability of cPSA, free‐to‐total PSA ratio (f/tPSA), free‐to‐complexed PSA ratio (f/cPSA), tPSA density of the whole prostate (PSAD), of the transition zone (tPSATZ), and cPSA density of the whole prostate (cPSAD) and of the transition zone (cPSATZ) to improve the power of PSA in detecting prostate cancer was evaluated using receiver operating characteristic (ROC) curves.

Results Of the 140 patients, 126 had histologically confirmed benign disease and 14 had prostate cancer. The cPSA alone had better specificity for detecting prostate cancer than had tPSA alone but the difference was not significant. The area under the ROC curve for f/cPSA was larger than those for all other variables. With a 93% sensitivity for detecting prostate cancer, a f/cPSA threshold of 25% would result in fewer unnecessary biopsies (40% f/cPSA specificity) than with all other PSA variables. The difference in the resolution was significant between f/cPSA and tPSA, cPSA, tPSAD and tPSATZ, but not with f/tPSA, cPSAD or cPSATZ. In patients with a prostate volume of < 30 mL, the cPSATZ showed better specificity for prostate cancer than tPSA alone.

Conclusion 

Measuring the level of cPSA and its derivatives may provide better differentiation of prostate cancer and benign disease than tPSA alone in patients with a tPSA level of 4.1–10.0 ng/mL.
A novel basic protein from human kidney which inhibits calcium oxalate crystal growth
Authors: Selvam R. , Kalaiselvi P.
Published: March 2003

Objectives To isolate calcium oxalate‐binding proteins from human kidney and characterize the functional properties.

Materials and methods Calcium oxalate crystals were prepared and allowed to interact at two different pH values with Triton‐extracted human kidney homogenate. The proteins in the homogenate were isolated and fractionated on a cellulose column, and purified by high‐performance liquid chromatography. The protein with the greatest oxalate binding activity at pH 4.5 was analysed for its amino‐acid composition and characterized by Scatchard plot analysis, crystal growth, nucleation and aggregation studies.

Results Three major protein fractions were eluted when calcium oxalate monohydrate was adsorbed at both pH values (designated as fractions I–III, according to their order of elution). The yield of fraction I and III was increased when adsorbed at an acidic pH. However, only fraction III had maximum oxalate binding activity at pH 4.5. When purified, this protein had maximum oxalate binding activity of ≈ 270 pmol/mg protein and a molecular weight of ≈ 23 kDa. Amino acid analysis showed that 18% of the total molar proportion was of basic amino acids, e.g. lysine and arginine, while acidic amino acids accounted for only 11%. Both alanine and glycine constituted ≈ 41% of the total molar proportion. Modifications to the lysine group abolished oxalate‐binding activity of the protein. The protein inhibited crystal growth by 82% at 0.8 µmol/L, while it inhibited the nucleation and aggregation of the crystals by 6% and 28%, respectively, at 49 nmol/L. The inhibition of both nucleation and aggregation was higher at pH 5.7 than at pH 7.4. Significantly, the protein induced the formation of intertwined calcium oxalate dihydrate crystals in a medium known to induce the formation of individual dihydrate crystals.

Conclusion The protein described here is the first reported basic inhibitor of calcium oxalate crystal growth with oxalate‐binding activity at pH 4.5 that modulates calcium oxalate crystallization. It is suggested that this protein may play a physiologically significant role in inhibiting stone formation in acidic urine.
Incidence of bone fracture in patients receiving luteinizing hormone‐releasing hormone agonists for prostate cancer
Authors: Hatano T. , Oishi Y. , Furuta A. , Iwamuro S. , Tashiro K.
Published: March 2003

Objective To investigate the incidence of bone fractures in patients receiving luteinizing hormone‐releasing hormone agonists (LHRH‐a) for prostate cancer (in whom a continued low testosterone level after the long‐term administration of these drugs reduces bone mineral density), and thus determine the risk of secondary osteoporosis.

Patients and methods Between 1994 and 1999, 218 patients (mean age 77.3 years) were treated for  6 months with LHRH‐a for prostate cancer; of these, 14 (6%) had a bone fracture during their treatment. Patients with fracture associated with motor vehicle accidents were excluded. The bone density in the third lumbar vertebra was meas‐ured using quantitative computed tomography. Osteocalcin, 1,25‐(OH)2 vitamin D, urinary type 1 collagen cross‐linked N‐telopeptides (NTx), parathyroid hormone and calcitonin were measured as metabolic markers.

Results The mean age of the patients with fracture was 78 years; the mean (range) interval from the start of treatment to fracture was 28 (11–46) months. There was no case of a bone fracture at the site of a metastasis from prostate cancer. The bone density was significantly lower in the patients with a fracture than in those without. Of the bone metabolic markers, NTx was higher in those with a fracture.

Conclusion There is a need to measure bone mineral density and bone metabolic markers periodically, and to evaluate secondary osteoporosis in patients receiving long‐term LHRH‐a for prostate cancer.
Results from different patient populations using combined therapy with alprostadil and sildenafil: predictors of satisfaction
Authors: Mydlo J.H. , Volpe M.A. , Macchia R.J.
Published: March 2003

Objective To evaluate the outcome of combined therapy (using intraurethral alprostadil and oral sildenafil) in private and clinic patients with erectile dysfunction, and thus assess predictors of satisfaction.

Patients and methods In all, 360 men were treated for erectile dysfunction using single and/or combined therapy, comprising 214 private‐practice and 166 clinic patients. Responses were evaluated using the International Index for Erectile Function (IIEF) questionnaire before and after treatment. Serum testosterone levels, education and socio‐economic status were also assessed. Group 1a consisted of 33 private patients and Group 1b of 24 clinic patients who tried the maximum dose of intraurethral alprostadil monotherapy initially, followed by the maximum dose of sildenafil monotherapy, and remained dissatisfied. Group 2a consisted of 32 private patients and group 2b of 31 clinic patients who tried the maximum dose of sildenafil monotherapy initially, followed by the maximum dose of alprostadil monotherapy, and were also dissatisfied. These two groups of 65 private and 55 clinic patients then underwent combined therapy.

Results The mean (
sd) score for erectile function was 24.1 (2) for combined therapy (a 123% improvement), and 19.8 (1.8) (83% improvement) and 15.2 (1.6) (41% improvement) for sildenafil and alprostadil monotherapies (P < 0.05 for both patient groups). The men also reported an improvement in their satisfaction with intercourse. However, at 18 months, 60 of the 65 private patients but only 40 of the 55 clinic patients continued with combined therapy; thus, the discontinuation rate was three times greater among clinic than among private patients. Furthermore, the private patients had an overall improvement in the satisfaction score of 128%, compared with 51% for the clinic patients.

Conclusion Although there were no significant differences in erectile function improvement within the two satisfied combined therapy groups, the differences in overall satisfaction and long‐term withdrawal rates suggests that other factors beside motivation must be involved for success, e.g. education, persistence, realistic expectations, and certain psychological factors. Combined therapy should be considered for those patients who have a suboptimal response to monotherapy and refuse or are not candidates for surgical options. Generally, those patients with a higher education, greater persistence and more realistic expectations were more satisfied with combined therapy.
A model to quantify encrustation on ureteric stents, urethral catheters and polymers intended for urological use
Authors: Choong S.K.S. , Wood S. , Whitfield H.N.
Published: March 2003

Objective To validate an encrustation model and to quantify encrustation on currently used urological devices and polymers intended for urological use.

Materials and methods An encrustation model was validated: (i) to measure the amount of calcium leaching from the glass model and from the polymer used; (ii) to determine whether the use of a single‐source or pooled urine produced similar results; (iii) to determine in vitro encrustation; and (iv) to compare the results of in vivo implantation of the same materials into the bladders of rodents with the in vitro results. A test polymer (a ureteric stent, a urethral catheter or a biomaterial) and a control silicone polymer were housed separately but received human urine from the same reservoir and under the same conditions (pH 6.0 and 37 °C) for 5 days. The amount of calcium encrustation on each polymer was measured using atomic absorption spectroscopy. Each experiment was repeated at least four times and the results expressed as an encrustation index, defined as the ratio of encrustation of the test and reference polymers.

Results The amount of calcium leaching from the glass model and polymers tested was insignificant. The use of a single‐source or pooled urine gave the same results in the encrustation model. The in vitro results correlated with in vivo implantation of disks into the bladders of rats. Among the commonly used ureteric stents tested, the Cook C‐Flex ureteric stents encrusted least. Hydrogel‐coated ureteric stents encrusted more than uncoated stents. The Bard polytetrafluoroethylene short‐term urethral catheter encrusted more than the Bard hydrogel‐coated long‐term catheter. A plasma‐activated surface modification of a synthetic biomaterial with hyaluronic acid encrusted less than silicone, a long‐term biomaterial widely regarded as the ‘gold standard’.

Conclusion This validated encrustation model is the first to quantify encrustation on currently available ureteric stents and urethral catheters. A novel coating for a biomaterial was identified using the encrustation model, and which encrusted less than silicone.
Cytoplasmic induction and over‐expression of cyclooxygenase‐2 in human prostate cancer: implications for prevention and treatment
Authors: Madaan S. , Abel P.D. , Chaudhary K.S. , Hewitt R. , Stott M.A. , Stamp G.W.H. , Lalani E.‐N.
Published: March 2003

Objective To assess the level and morphological distribution of cyclooxygenase (COX)‐1 and ‐2 in human prostates and to determine any association with the Gleason grade of prostate cancer.

Materials and methods The study comprised 30 samples from patients with benign prostatic hyperplasia (BPH) and 82 with prostate cancer. Immunohistochemistry was used to assess the expression of COX‐1 and ‐2, and 13 samples were also assessed using immunoblotting (six BPH and seven cancers).

Results For both BPH and prostate cancer, COX‐1 expression was primarily in the fibromuscular stroma, with variable weak cytoplasmic expression in glandular/neoplastic epithelial cells. In contrast, COX‐2 expression differed markedly between BPH and cancer. In BPH there was membranous expression of COX‐2 in luminal glandular cells and no stromal expression. In cancer the stromal expression of COX‐2 was unaltered, but expression by tumour cells was significantly greater (P = 0.008), with a change in the staining pattern from membranous to cytoplasmic (P < 0.001). COX‐2 expression was significantly higher in poorly differentiated than in well differentiated tumours (P < 0.001). These results were supported by immunoblotting, which showed similar levels of COX‐1 in both BPH and cancer, but four times greater expression of COX‐2 in cancer than in BPH.

Conclusion This is the first study to assess the co‐expression of COX‐1 and COX‐2 proteins in benign and malignant human prostates, and showed the induction and significantly greater expression of COX‐2 in cancer, which was also associated with tumour grade. The regular use of nonsteroidal anti‐inflammatory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX‐2 inhibitors in the prevention and treatment of prostate cancer.
Percutaneous embolization of the failed renal allograft in patients with graft intolerance syndrome
Authors: González‐Satué C. , Riera L. , Franco E. , Escalante E. , Dominguez J. , Serrallach N.
Published: March 2003

Objective To analyse the circumstances, results and complications of percutaneous embolization in failed renal grafts that are not tolerated, to avoid surgical graft removal in selected patients.

Patients and methods The study included 33 patients (mean age 42 years,
sd 13.9) whose renal grafts failed between 1990 and 1999. The patients underwent percutaneous embolization of their renal transplant for graft intolerance syndrome. The allograft was left in situ after failure for a mean (
sd) of 9.9 (6.5) months. The subsequent hospital stay, the appearance of complications and the final results were assessed.

Results Post‐embolization syndrome (fever for 2–5 days) appeared in 20 (61%) of the patients; the clinical intolerance resolved in 28 (85%). The embolization was unsuccessful in five of the 33 patients (15%) and they required graft removal. The mean (
sd) hospital stay was 5 (2) days; there were no major complications from graft embolization.

Conclusions Graft embolization avoids kidney removal in many patients with failed and rejected transplants, with low rates of morbidity. Surgical graft nephrectomy was useful when graft intolerance syndrome persisted after embolization.
Comparison of the effects of novel antimuscarinic drugs on human detrusor smooth muscle
Authors: Yono M. , Yoshida M. , Takahashi W. , Inadome A. , Ueda S.
Published: March 2003

Objective To evaluate the effects of tolterodine, vamicamide and temiverine, novel antimuscarinic drugs developed for the treatment of frequency and urinary incontinence, on human detrusor smooth muscle.

Materials and methods Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy for malignant bladder tumour. Using an organ‐bath technique, the effects of various drugs on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in the detrusor strips were investigated.

Results Carbachol (0.001–10000 µmol/L) caused concentration‐dependent contractions in human detrusor smooth muscles. Tolterodine (0.01–10 µmol/L), vamicamide (0.01–10 µmol/L), temiverine (0.01–1 µmol/L) and atropine (0.001–1 µmol/L) caused parallel shifts to the right of the concentration‐response curves to carbachol. All slopes for the regression line of Schild plots were close to unity, and the rank order of pA2 values was atro‐pine = tolterodine > vamicamide > temiverine. Tolterodine, vamicamide and atropine did not inhibit the maximum contractile responses to carbachol, while temiverine (10 µmol/L) significantly inhibited the maximum contractions. Tolterodine (0.001–1 µmol/L) and vamicamide (0.01–10 µmol/L) did not inhibit the KCl‐ (80 mmol/L) and CaCl2‐induced (5 mmol/L) contractions, while temiverine (0.01–10 µmol/L) significantly inhibited the contractions. Electrical field stimulation (2–60 Hz) caused frequency‐dependent contractions in human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 1 µmol/L atropine, tolterodine and vamicamide did not inhibit the contractions induced by electrical field stimulation at all frequencies, while temiverine (10 µmol/L) significantly inhibited the contractions.

Conclusion Tolterodine and vamicamide inhibited contractions of human detrusor smooth muscles only through their antimuscarinic action, while temiverine had both antimuscarinic and calcium‐antagonist actions. Furthermore, these novel drugs have different efficacies and potencies for inhibiting human detrusor smooth muscle.