Pharmacological modulation of ureteric peristalsis in a chronically instrumented conscious pig model: effect of adrenergic and nitrergic modulation.

PURPOSE: To evaluate the role of adrenergic and nitrergic signaling on ureteric peristaltic frequency and contraction force in vivo using a large animal model. METHODS: Twelve female pigs (72 ± 4 kg) were chronically instrumented with an electronic pressure-monitoring catheter in the right ureter. Nephrostomy, cystostomy, and arterial and venous catheters were left in situ. Ureteral peristalsis was recorded before and after the administration of propranolol, isoprenaline, doxazosin, urapidil, phenylephrine, LNNA (Nω-nitro-L-arginine), and L-arginine. RESULTS: α1-Adrenergic receptor stimulation resulted in an increased P max and peristaltic frequency. However, α1-inhibition decreased P max alone. Similarly, ß-adrenergic stimulation decreased P max and peristaltic frequency, whereas ß-inhibition increased only P max. LNNA administration increased P max in the distal ureter and hydrostatic pressure in the pyelocalyceal system. L-Arginine did not affect P max or frequency, but resulted in a significantly higher diuresis. Either agonist or antagonist of NO did not affect peristaltic frequency and length of contraction. CONCLUSIONS: Activation of α- and ß-adrenergic receptors, respectively, stimulates and inhibits ureteric peristalsis. The biological effect of NO on ureteric motility is regionally determined and corresponds to the distribution of NOS-positive nerves. Inhibition of NOS activity increases P max in the distal ureter and tonic activity of the ureteric muscle resulting in higher hydrostatic pressure in the renal pelvis.

Randomized double-blind, placebo controlled safety study of a low molecular weight heparinoid in patients undergoing transurethral resection of the prostate.

In preparation for an efficacy study, the effect of the low molecular weight heparinoid Org 10172 on postoperative blood loss was assessed in a randomized double-blind, placebo controlled study in patients undergoing transurethral resection of the prostate (TURP). Org 10172 and placebo were given twice daily as i.v. injection for three postoperative days starting one hour preoperatively. Three doses of Org 10172 (800, 1600, and 2400 anti-Xa units b.d.) were evaluated against placebo in three consecutive patient blocks respectively. Each block consisted of 20 patients, 15 receiving Org 10172 and 5 patients placebo. The study was discontinued after 9 patients of the third block had completed the protocol because of excessive urinary blood loss. Data analysis showed a dose-dependent increase in postoperative haemoglobin loss, this was not significant for the 800 anti-Xa units b.d. dosage but was significant in those patients treated with 1600 (p less than 0.05) and 2400 anti-Xa units b.d. (p less than 0.01). It was concluded that the heparinoid Org 10172 caused a dose dependent increase in urinary blood loss following TURP.

Brachytherapy with transperineal (125)Iodine seeds for localized prostate cancer.

BACKGROUND AND PURPOSE: To analyze the treatment results of transperineal (125)Iodine seeds in localized prostate cancer. PATIENTS AND METHODS: Between 1985 and 1996, 102 patients with T1-T2 N0 prostate cancer were treated with transperineal (125)Iodine seed implants at the Academic Medical Centre in Amsterdam. Tumours were classified as T1c in four patients, T2a in 73 patients and T2b in 25 patients. The mean pre-treatment PSA was 17 ng/ml. The (125)Iodine seeds were implanted transperineally under transrectal ultrasound guidance. The mean prostate volume was 31 ml (range 15-48 ml). An average of 49 seeds (range 29-74) was implanted. The dose to the periphery of the prostate was 160 Gy. Until 1988, 27 patients had additional external pelvic irradiation to a dose of 40 Gy in 20 daily fractions of 2 Gy. RESULTS: The 5- and 7-year actuarial survival rates were 77 and 63%, respectively (median 102 months). Ten patients (9.5%) died from prostate cancer. The 5- and 7-year clinical progression rates were 12 and 17%, respectively. Biochemical failure rates at 5 and 7 years were 39 and 44%, respectively. Age, alkaline phosphatase, creatinine, differentiation grade, additional treatment, staging procedure, number of seeds, prostate volume, treatment period and PSA were analyzed as prognostic factors. Only pre-treatment PSA was a prognosticator of clinical and biochemical outcome but not of survival. Biochemical control at 6 years varied from 30% for pre-treatment PSA values higher than 20 ng/ml to 95% for values < or =8 ng/ml. Forty-one out of 49 patients who were sexually active before brachytherapy maintained sexual function during the follow-up. Complete urinary incontinence occurred in one patient. No rectal complications were seen in patients receiving brachytherapy alone. CONCLUSIONS: Transperineal (125)Iodine seeds brachytherapy in localized prostate cancer achieves a good clinical control and overall survival with acceptable late toxicity. Biochemical failure was strongly correlated to the pre-treatment PSA value.

Sexual dysfunction in men with lower urinary tract symptoms.

The conventional view that sexual function is not adversely affected by lower urinary tract symptoms (LUTS), assumed to be caused by enlargement secondary to benign prostatic hyperplasia (BPH), was investigated in this study of 423 men aged 40 years and over in a community population in the UK and 1271 urology clinic attenders aged 45 years and over in 12 countries, using the ICSmale and ICSsex questionnaires. Sexual dysfunction was found to be common: in the community, age standardized prevalences of reduced rigidity of erections were 53%, reduced ejaculation 47%, and pain on ejaculation 5%; in clinic men, age standardized prevalences of reduced rigidity of erections were 60%, reduced ejaculation 62%, and pain on ejaculation 17%. Sex lives were reported to be spoiled by LUTS in 8% of community men and 46% in the clinic. There were negative trends for age in the extent to which clinic men were bothered by these symptoms, although older men were still very concerned. Significantly raised odds ratios of sexual dysfunction were found in those with LUTS, especially storage symptoms associated with incontinence. Urinary flow rates were not associated with sexual symptoms. Sexual dysfunction is, therefore, strongly associated with LUTS, is a matter of concern to the men affected, and should be taken into account when managing patients with LUTS.

Is preoperative transrectal ultrasonography of value in localised prostatic carcinoma? A blind comparative study between preoperative transrectal ultrasonography and the histopathological radical prostatectomy specimen.

Digital rectal examination (DRE) for staging is subjective and unreliable. Understaging has been reported in 25-72% and clinical overstaging of T3 tumors varies from 24-50%. In the present study of 15 patients, transrectal ultrasound (TRUS) staging was compared, in a blind comparative fashion, with pathological staging of the surgical specimen. Multifocal lesions were present in 8/15 patients (53%). A distinction was made between capsular involvement and 'clear' capsular penetration. TRUS was more sensitive in predicting capsular involvement than DRE (83% vs 17%), but the specificity was low (67% vs 100%). If capsular perforation was considered, the sensitivity and specificity of TRUS are 43% and 91%, respectively. Sensitivity and specificity for seminal vesicle tumor involvement by TRUS was 63% and 86%. Using TRUS the overall staging was improved by 33% compared with DRE and therefore TRUS is considered to be a valuable acquisition in localising and staging prostate cancer.

Multichannel urethral pressure profiles: reproducibility and three-dimensional representation.

Urethral pressure profilometry (UPP) is used to investigate the pressure distribution in the urethra. Single UPP is dependent on the orientation of the catheter during the study. To circumvent this problem, we developed a system for multichannel profilometry (MCUPP) that can be used in daily clinical practice. In the study reported in this article, 29 healthy female volunteers (mean age 34.6 years) underwent MCUPP. The mean time needed to make five pressure profiles ranged from 4 to 12 minutes (mean 7.6). The system is patient- and user-friendly. The volunteers scored the discomfort on a 1 to 10 scale, with 10 meaning no discomfort at all, rendering a mean score of 7.6. The Symmetry Index (SI) is a calculated variable expressing the asymmetry in the pressure profiles. An SI of 1 means a completely symmetrical pattern of pressure distribution. The mean SI for the whole group was 0.7 (range 0.407-0.930). The standard deviation was 0.109. Within-subject SI was highly reproducible (Greenhouse-Geisser epsilon = 0.98292).

A view on the anatomy of the ureterovesical junction.

Macro- and microscopic dissection of 8 adult and 2 fetal human bladders was undertaken in two directions as part of a study to evaluate ureterovesical junction function. In the trigonal region the detrusor muscle consists of 3, more or less triangular layers. Both ureters are only loosely enveloped by a fibromuscular sheath of mainly bladder origin. This design allows for easy movement of the ureters on their oblique course through the bladder wall. The ureteral muscle fibers play only a minor part in the sheath or join the detrusor muscle. The majority fan out to end at the bladder mucosa or intermingle with fibers originating from the opposite ureter. Since an intricate muscular structure can be demonstrated, an active anti-reflux muscular component in the normal human bladder seems plausible. A classic ureteral sphincter mechanism does not exist. Our findings are discussed and compared with data from the literature.

Ten years survival after recurrent intracranial metastases from a renal cell carcinoma.

The clinical behaviour of renal cell carcinoma is often unpredictable. We report a patient who underwent three palliative resections over 10 years for recurrent intracerebral metastases from a renal cell carcinoma.

A study of concentrations of trimethoprim-sulphamethoxazole in the human prostate gland.

The ability of trimethoprim (TMP) and sulphamethoxazole (SMX) components of co-trimoxazole to penetrate the human prostate gland was investigated. After a single 4-tablet dose TMP was evenly distributed between prostate and plasma, whereas SMX was mainly associated with plasma. Following a week's therapy significant accumulation of TMP was seen in the prostate relative to plasma whereas SMX although still associated with plasma had increased drug levels in prostate compared with the single dose study. It is concluded that co-trimoxazole produces effective antibacterial levels in the human prostate and has indications in the treatment of prostatitis.

Leiomyosarcoma of the renal vein: a case report.

We report a rare case of leiomyosarcoma of the renal vein. There have been only 5 other such cases reported in the literature. Special attention is focused on the diagnostic problems and the paucity of presenting symptoms. The literature is reviewed briefly.

Adenocarcinoma of the kidney in childhood.

Renal adenocarcinoma in children is a rare tumor. A case report is presented and review of the available literature. There is no difference in symptomatology, therapy and prognosis between children and adults.

Functional anatomy of the human ureterovesical junction.

BACKGROUND: The valve function of the ureterovesical-junction (UVJ) is responsible for protection of the low pressure upper urinary tract from the refluxing of urine from the bladder. Controversy about the microanatomy of the human ureterovesical-junction persists. METHODS: Ten (3 male and 7 female) fresh cadaveric bladders (mean age 70 years old) were studied. The bladders were fixed within 24 hours postmortem, frozen, and serially sectioned. Acetyl- and butyryl- (nonspecific) cholinesterase activity were visualised as described by Karnovsky and Roots. The three-dimensional distribution of the different muscle groups participating in the formation of the UVJ was reconstructed. RESULTS: Three different muscle groups were identified: (1) the detrusor muscle and the deep trigone were mainly acetylcholinesterase-positive, (2) the inner and outer layer of the ureteric muscle were butyrylcholinesterase-positive and merged into a single longitudinal layer at the level of the UVJ and form the superficial trigone distally to the ureteric orifices, and (3) the muscularis mucosae is a discontinuous butyrylcholinesterase-positive layer in the bladder that is absent from the trigone. No evidence of any muscular connection was found between the ureter and bladder musculature. CONCLUSIONS: The anatomy of the UVJ as observed by us suggests the following model of the ureteric peristalsis. The urine bolus arrives in the ureteric lumen at the UVJ level. The ureter can only shorten its length, slides freely in its tunnel, and discharges the urine bolus in the bladder cavity. Ureteric constriction due to the peristalsis and thickening of the contracted portion of the ureter prevents the upstream leakage. Distal spreading of the ureteric "peristalsis" in the superficial trigone increases the submucosal ureteric length and prevents reflux.

An in vivo endoluminal ultrasonographic study of peristaltic activity in the distal porcine ureter.

PURPOSE: Experiments were performed to quantify the duration and frequency of ureteric peristaltic activity in the laparotomized and non-laparotomized pig in its virgin and postinstrumented states. MATERIALS AND METHODS: Pigs (n = 10) in a steady state of hydration were studied under halothane anesthesia in two groups. The study was undertaken in two separate sessions at a week's interval. In group I laparotomy and vesicotomy were undertaken to obtain ELUS images. In group II, peristalsis was studied using an ELUS probe introduced through the working channel of a 22F rigid cystoscope. Peristalsis was visualized as a periodic diameter-change of ureter and recorded (for approx. 30 minutes) on videotape after an initial period of adaptation of approx. 30 minutes. RESULTS: The ureter acts like a pump discharging urine into the bladder through peristaltic activity. ELUS imaging of ureteric peristalsis correlated well with "eyeballing" of the passage of peristalsis through a ureter (group I). The shortest peristaltic activity in group I was 6.0+/-2.0 seconds in the non-instrumented- and 5.1+/-1.4 seconds in the instrumented ureter. In group II it was 6.8+/-1.5 seconds in the non-instrumented- and 6.4+/-1.5 seconds in the instrumented ureter. Chronic dilatation of ureter led to decrease in peristalsis frequency. Interestingly, acute dilatation caused an increase in ureteric peristalsis frequency. CONCLUSIONS: Ureteric peristalsis acts as a pump discharging urinary boluses (intraluminal fluid load) unidirectionally into the bladder. ELUS provides us an opportunity to quantify and study ureteric peristalsis.

Anatomy of ureterovesical junction and distal ureter studied by endoluminal ultrasonography in vitro.

PURPOSE: The emerging technique of endoluminal ultrasonography (ELUS) provides a new modality for endoscopic visualization of the urinary tract which needs to be further evaluated. We studied the normal anatomy of distal ureter and ureterovesical junction using ELUS. MATERIALS AND METHODS: An assessment of in vitro ELUS ureteric images undertaken at 1 mm. intervals from 8 fresh human cadaver pelvis blocs of bladder and distal ureter were compared with findings of serial histological sections of the same specimens (stained for cholinesterase isoenzymes) to assess the degree of correlation. Computer-assisted 3D reconstructions were made. RESULTS: The different components (ureteric, detrusor and periureteric tissue) of the UVJ could be identified on the basis of echogenicity and form, but differentiation between the respective muscle layers in the wall of the ureter or of the detrusor was not possible. Nevertheless, ureteric volume measurements and an assessment of transmural ureteric length and the angle of passage through the bladder wall were possible. CONCLUSIONS: ELUS is able to differentiate between the ureteric and detrusor muscle and the UVJ gross anatomy can be reconstructed. ELUS technology, however, fails to differentiate between individual muscular layers of the ureter or the detrusor. Further improvement in ELUS is mandatory.

Fibrous pseudotumor of the tunica vaginalis testis.

The incidence of fibrous pseudotumor of the tunica vaginalis testis is rare. It is a benign, fibroproliferative process with hyalinization and sometimes with focal calcification. In most cases malignancy is suspected although by careful physical examination it may be possible to establish the diagnosis pre-operatively. The best form of therapy is frozen section biopsy of the pseudotumor followed by excision; including if necessary the tunica vaginalis. If the pseudotumor is locally extensive an epididymectomy is sometimes necessary. A study of the literature reveals that because of the rarity of this lesion orchidectomy appears to have been performed in most cases. A case report of a patient with fibrous pseudotumor of the tunica vaginalis testis is presented.

Microvascular surgical orchiopexy in the treatment of high-lying undescended testes.

Extensive laboratory experiments in animals have led us to believe that autotransplantation of the testis in the human is feasible. To date, nine of our patients (aged 4-13 years) with undescended intra-abdominal testes have undergone autotransplantation. Using a microvascular surgical technique to anastomose the testicular vessels to the inferior epigastric vessels, it has been possible to place the testis in a scrotal position in every case. No postoperative complications have been noted. Follow-up varied from 9 to 18 months and no atrophy of the testis was observed in this period. Doppler investigations on all of the transplanted testes continue to demonstrate good arterial flow. The aim of surgery on the undescended testis is not only to increase the chances of fertility and to diminish the possibility of malignant transformation but also, more importantly perhaps, to prevent possible abnormal psychosexual development in the child.