Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety.

PURPOSE: Neuromodulation of sacral nerves has shown promising results in correcting voiding dysfunction. We report the results of a multicenter trial designed to assess the efficacy of sacral nerve neuromodulation in patients presenting with refractory urinary urgency-frequency. MATERIALS AND METHODS: A total of 51 patients from 12 centers underwent baseline assessment, including a detailed voiding diary, urodynamic evaluation and percutaneous test stimulation of the sacral nerves at S3 and/or S4. All patients enrolled in the study had undergone prior conventional treatment, such as pharmacotherapy, hydrodistention and surgical intervention, which failed. All patients demonstrated a satisfactory response to trial stimulation and were randomly divided into a stimulation group (25 patients) and a control group (26). A sacral nerve stimulation device was implanted after 6 months in the control group. Patients were followed at 1, 3 and 6 months, and at 6-month intervals for up to 2 years after implantation of a neuroprosthetic InterStim* system. dagger The study variables included the number of voids daily, volume voided per void and degree of urgency before void. RESULTS: Compared to the control group, 6-month voiding diary results demonstrated statistically significant improvements (p <0.0001) in the stimulation group with respect to the number voids daily (16.9 +/- 9.7 to 9.3 +/- 5.1), volume per void (118 +/- 74 to 226 +/- 124 ml.) and degree of urgency (rank 2.2 +/- 0.6 to 1.6 +/- 0.9). Patients in the control group showed no significant changes in voiding parameters at 6 months. Significant improvements in favor of the stimulation group were noted in various parameters with respect to water cystometry and quality of life (SF-36). At 6 months after implant, neurostimulators were turned off in the stimulation group and urinary symptoms returned to baseline values. After reactivation of stimulation sustained efficacy was documented at 12 and 24 months. CONCLUSIONS: Neuromodulation of the sacral nerves is an effective, safe therapy that successfully treats significant symptoms of refractory urgency-frequency.

Measurement of thermal effects on the optical properties of prostate tissue at wavelengths of 1,064 and 633 nm.

BACKGROUND AND OBJECTIVE: The extent of thermal injury during laser prostatectomy is dependent on the light distribution in laser-irradiated tissue. As tissue is irradiated, the optical properties change as a function of temperature due to an alteration of molecular and cellular structure. The purpose of the present study was to determine how the exposure of both fresh and previously frozen canine prostate tissue to elevated temperatures affects the optical properties. STUDY DESIGN/MATERIALS AND METHODS: Optical properties were measured by using a double integrating sphere spectrophotometer with an inverse adding-doubling algorithm. Measurements were made at two wavelengths (1,064 nm and 633 nm) on samples heated in a waterbath in 5 degree-10 degree increments for 10 min through a 50 degrees C temperature range. RESULTS: Upon coagulation, the absorption coefficient of fresh tissue decreased from the baseline measurement for both wavelengths (0.027 +/- 0.003 to 0.019 +/- 0.002 for lambda = 1,064 nm; 0.073 +/- 0.007 to 0.061 +/- 0.006 for lambda = 633 nm). However, the scattering coefficient increased sharply from the baseline measurement following coagulation (3.06 +/- 0.26 to 6.05 +/- 0.29 for lambda = 1,064 nm; 4.89 +/- 0.23 to 7.22 +/- 0.30 for lambda = 633 nm). Thermal coagulation occurred during exposure to temperatures between 60 degrees C and 70 degrees C. CONCLUSION: Data obtained in this study indicate that thermal coagulation of tissue alters the optical properties. The extent to which these changes occur was found to be dependent on wavelength and freshness of tissue. These results are significant because they suggest how thermally induced changes in the optical properties may limit the depth of light penetration in tissue thus compromising treatment.

Evaluation of renal resistive index, maximum velocity, and mean arterial flow velocity in a hydronephrotic partially obstructed pig model.

RATIONALE AND OBJECTIVES: The authors investigate, in a controlled pig model, the usefulness of Doppler sonographic measurements of resistive index (RI), maximum velocity (Vmax), and mean velocity (Vmean) in diagnostic evaluation of the partially obstructed kidney. METHODS: Seven female pigs underwent surgical partial unilateral renal obstruction at the ureteropelvic junction. Doppler parameters of RI, Vmax, and Vmean were measured preoperatively and postoperatively in obstructed and contralateral nonobstructed kidneys. The General Linear Model multivariate analysis of variance was used for statistical analysis of data. RESULTS: There was no significant difference in the preoperative control values of RI (P = 0.71), Vmax (P = 0.27), and Vmean (P = 0.12). There was a statistically significant decrease in the Vmax and Vmean after postoperative day 5 in the obstructed kidney compared with the contralateral nonobstructed kidney (P = 0.01 and 0.03, respectively). There was no statistically significant difference in RI during the study. CONCLUSIONS: In this study, RI was not a reliable indicator of partial renal obstruction. Measurements of maximal and mean blood flow velocities reached discriminatory significance only after the fifth postobstructive day, proving insensitive in the immediate postobstructive period. Vmax and Vmean demonstrated a decrease in the partially obstructed renal collecting system after 5 days of obstruction and may serve as useful parameters in the evaluation of obstruction after the immediate acute period, when compared with a nonobstructed contralateral system.

Techniques of coagulation laser prostatectomy for narrow divergence angle fibers.

Although laser prostatectomy has become an accepted technique for the treatment of obstructive prostatism, considerable debate remains about which laser prostatectomy method to use in various treatment situations. This article discusses the different methods of noncontact side-firing coagulation laser prostatectomy using narrow divergence angle fibers (< 30 degrees). Static treatment strategies that have been successfully employed with widely divergent beams are not appropriate for fibers producing narrow divergence angle beams. Narrow divergence angle beams produce a small diameter spot on the prostatic urethra and far larger power density. Additionally, neodymium/yttrium aluminum garnet light scatters relatively poorly within prostatic tissue. Most light continues along the path of through transmission until ultimate tissue absorption and conversion into heat. The width and total volume of the coagulated lesion is therefore limited when using a narrow divergence angle fiber to produce static lesions. Probe movement is essential. Rapid (> 2 mm/s) probe movement produces only superficial coagulation. An initial dwell period of approximately 3 s is also important to maximize coagulated tissue volume. Scanning strategies where the fiber is moved through the prostatic urethra in longitudinal and radial directions are discussed and compared. Radial and longitudinal scanning methods produce similar coagulation defects. Treatment using a rocking motion within a limited volume of tissue may increase coagulation depth. No technique is ideal for all clinical situations. Vaporization prostatectomy or contact laser transurethral incision of the prostate is appropriate for primary treatment of glands < 30 g or as adjunctive therapy to facilitate early catheter removal. Alternative treatment methods are compared to noncontact coagulation prostatectomy.

Evaluation and management of the urologic consequences of neurologic disease.

Neurologic disorders create important functional urinary tract abnormalities. Loss of bladder reflex inhibition and coordination due to neurologic disease or injury to higher centers may lead to morbidity such as recurrent urinary tract infection, hydronephrosis, urinary tract stones and loss of renal function. This paper discusses neurogenic bladder disease using a descriptive urodynamic format. The importance of detrusor hyperreflexia and internal and external sphincter dyssynergia are discussed in detail. Finally, a practical clinical management plan is discussed for patients with urologic dysfunction due to cerebrovascular accident, Parkinson's disease, multiple sclerosis, spinal cord injury, and peripheral neuropathy.

Prevention and treatment of incontinence after radical prostatectomy.

Postoperative complications after radical prostatectomy have only recently been studied in a formal prospective manner. A survey of existing literature yields widely disparate rates of postoperative incontinence. Classically, about 5% of patients were believed to be incontinent. More recent studies that involve patient questionnaires and a specific continence history indicate that nearly 30% of patients experience some urinary leakage with activity. Evolving new operative techniques such as modified apical dissection and construction of a tubularized neourethra have potential to improve continence rates considerably. Patients who do experience urinary incontinence should be offered appropriate evaluation and treatment. In addition to cystourethroscopy, all patients should undergo cystometry and Valsalva leak-point testing to differentiate sphincteric dysfunction from detrusor instability. Injection of bovine cross-linked collagen into the preexternal sphincter zone or implantation of the artificial urinary sphincter are options for treatment of intrinsic sphincter dysfunction. Detrusor instability is best treated with pharmacotherapy. This article discusses the details of prevention, evaluation, and treatment of postprostatectomy incontinence.

Laser prostatectomy devices and their tissue effects.

Laser systems used for prostatectomy may be right-angle (sidefiring) devices, which are either refractive or reflective, or contact devices. The tissue physics of these systems differ, and as a result, there are very real differences in the optimal exposure techniques. An understanding of the device being used is essential for producing a satisfactory result.

Intrapelvic pressure monitoring in the partially obstructed porcine kidney.

OBJECTIVES: The diagnosis of urinary obstruction in newborns and infants remains difficult because the diagnostic studies available at present are fraught with many problems. It is our premise that precise measurement of renal pelvic pressures under physiologic conditions in patients with urinary tract dilation will allow diagnosis of obstruction and prediction of further renal damage. This study evaluates an intrapelvic pressure monitoring system. METHODS: Four porcine subjects had partial ureteropelvic junction obstruction created surgically; two subjects were used as controls. Doppler ultrasound and MAG-3 furosemide renography were performed preoperatively and each week pressures were measured with a Millar 5 F solid-state pressure transducer and the analog signals were converted on line to digital information to allow signal processing and later data analysis. Antegrade nephrostograms were obtained at the same sitting and showed that the model remained stable over time. Measurements were obtained at physiologic flow rates as well as at the standard Whitaker infusion rate of 10 cc/min. RESULTS: Thirteen pressure studies were performed on 9 kidneys. Each study was classified as normal (4), partial obstruction (8), or total obstruction (1), based on ultrasound and nephrostogram criteria. The normal units had baseline pressures of 4.12 +/- 0.94 cm water (H2O), which increased to 9.12 +/- 1.38 cm H2O with infusion. In the partially obstructed group, baseline was 16.4 +/- 3.83 cm H2O and increased to 35.3 +/- 15.9 cm H2O with infusion. The kidney with total obstruction showed a baseline pressure of 27 cm H2O, which increased to 68 cm H2O with infusion. These pressure measurements were also compared to furosemide renography. CONCLUSIONS: Intrapelvic pressures correlated well with conventional ultrasound and nephrostogram in the evaluation of partial obstruction. However, the results of furosemide renography and the Whitaker test were quite variable and did not accurately define partial obstruction or correlate with intrapelvic pressure. The Millar solid-state transducer monitoring system is an accurate method of evaluating the intrapelvic pressure and could possibly become a standard for diagnosing significant urinary obstruction against which other studies can be evaluated.

Urological manifestations of sacrococcygeal teratoma.

A review was done of 29 patients diagnosed with sacrococcygeal teratoma between 1978 and 1991. Urological disorders included total urinary retention (6 patients), hydronephrosis (6), hydrocele (4) and undescended testis (1). Ultrasonography and voiding cystourethrography were performed on the 6 patients in total urinary retention. These studies revealed cystic retrorectal lesions frequently with intralesional calcifications, and anterior and superior displacement of the bladder. Bladder wall trabeculation occurred in 2 of these 6 patients, and 4 had moderate or severe hydronephrosis. Upper urinary tract dilatation was found in 2 patients not in total retention. Hydronephrosis appeared to be related to poor bladder emptying and presumably high intravesical pressures, since each case resolved spontaneously after tumor resection. No primary upper tract anomalies were identified.

Long-term corneal retention of a plant foreign body.

A fragment of sunflower stalk had been retained in the cornea of a 71-year-old man for 58 years. During initial healing of the wound, which included formation of a retrocorneal membrane over the foreign body in the anterior chamber, there was probably loss of endothelial cells. This probably predisposed the cornea to the endothelial decompensation that occurred following cataract extraction and implant of an intraocular lens 56 years after the foreign body first appeared in the cornea.

Calcium-accentuated ischemic damage during reperfusion: the time course of the reperfusion injury in the isolated working rat heart model.

The purpose of this study was to determine the time course of calcium-induced postischemic reperfusion injury to the myocardium, using an initial short-term calcium-enriched reperfusion solution. The isolated rat heart model was subjected to 30 min of normothermic potassium cardioplegia-induced ischemic arrest. Control hearts received normal calcium Krebs-Henseliet buffer (KHB) reperfusion. Experimental hearts were challenged with 10 min of calcium-enriched (KHB) reperfusion starting at 0, 1, 2, 5, 15, and 30 min after the beginning of reperfusion. Aortic flow recovery 60 min after reperfusion was used to determine functional recovery. Control hearts recovered 82 +/- 3% of preischemic aortic flow. Hearts which received calcium challenge at 0 and 1 min after the start of reperfusion recovered 43 +/- 4 and 69 +/- 3% of preischemic aortic flow, respectively (P less than 0.01 and P less than 0.05, respectively). Hearts which received calcium challenge 2, 5, 15, and 30 min after reperfusion recovered 75 +/- 2, 80 +/- 2, 85 +/- 2, and 83 +/- 2% of preischemic aortic flow, respectively. Our results indicate that the postischemic myocardium is very susceptible to calcium-accentuated ischemic damage during the initial period of reperfusion. The postischemic heart, however, quickly recovers its ability to withstand a calcium challenge. Five minutes after the start of reperfusion the heart is not influenced by calcium challenge.

Terminal magnesium cardioplegia: protective effect in the isolated rat heart model using calcium accentuated ischemic damage.

We have developed a modified isolated working rat heart model to study the effect of potassium and magnesium cardioplegia given just prior to reperfusion, "terminal cardioplegia," on preservation of aortic flow following a standard ischemic insult. The model incorporates a short-term calcium challenge at the beginning of reperfusion to accentuate ischemic injury. All hearts were given initial potassium cardioplegia and subjected to 30 min of normothermic ischemia. Terminal cardioplegia was given for the 2 min prior to reperfusion. Calcium-challenged hearts were reperfused initially with calcium-enriched reperfusate and then switched to standard reperfusate. Aortic flow prior to and 60 min after ischemia was used to determine functional protection. Hearts recovered 82 +/- 3% of preischemic aortic flow when reperfused with normocalcemic reperfusate. When the initial reperfusate was enriched with calcium, aortic flow was only 43 +/- 4% of control. Hearts given terminal magnesium cardioplegia and then challenged with calcium-enriched reperfusate recovered 79 +/- 4% of control aortic flow. Hearts given terminal potassium cardioplegia recovered only 53 +/- 5% of control aortic flow when challenged with calcium-enriched initial reperfusate. Our results indicate that the recovery of aortic flow is significantly reduced by short-term postischemic calcium challenge. This damage is blocked by terminal magnesium cardioplegia, but not by terminal potassium cardioplegia.

Disposition of the aromatic amine, benzidine, in the rat: characterization of mutagenic urinary and biliary metabolites.

The mutagenic and carcinogenic aromatic amine, benzidine (BZ), underwent extensive biotransformation in the rat. Three days after po (5.0 mg/kg) or iv (2.5 mg/kg administration of [14C]BZ, 90% of the radiolabel had been excreted in the urine (25%) and feces (65%); 7% was recovered in the animal. As the dose was increased from 0.5 to 50 mg/kg, the percentage of the dose excreted in urine increased twofold. In distribution studies, a major portion of the iv dose accumulated in the intestinal tract due to the excretion of 71% of the administered radiolabel in bile. The liver, which is a primary target organ of BZ carcinogenicity in rats, contained a higher concentration of radiolabel than other tissues studied. A minimum of 17 urinary and/or biliary metabolites were separated by HPLC. The major metabolites were N-acetyl-BZ(ABZ), N,N'-diacetyl-BZ(DABZ), BZ-N-glucuronide, ABZ-glucuronide, N-OH-DABZ glucuronide, 3-OH-DABZ glucuronide, and a glutathione conjugate of DABZ (3-GSH-DABZ). At low doses (0.5 to 5 mg/kg), 3-OH-DABZ glucuronide, 3-GSH-DABZ, and DABZ were the major urinary or biliary metabolites. However, at higher doses (50 mg/kg), N-OH-DABZ glucuronide, which was a minor metabolite at low doses, became a major urinary and biliary metabolite. Several urinary and biliary metabolites displayed significant mutagenicity in the Salmonella typhimurium (strain TA98)-liver S9-beta-glucuronidase assay. However, N-OH-DABZ glucuronide exhibited a mutagenic potency 10X greater than the other urinary metabolites. Results of these studies demonstrate that BZ is rapidly metabolized via N-acetylation, N-hydroxylation, and aromatic hydroxylation to a variety of mutagenic metabolites which are excreted in urine or bile primarily as glucuronide and/or glutathione conjugates. The most potent mutagen studied was also a major urinary and biliary metabolite.

Metabolism, distribution, and excretion of the carcinogenic aromatic amine, 3,3'-dimethoxybenzidine in the rat. Formation of mutagenic urinary and biliary metabolites.

The carcinogenic aromatic amine 3,3'-dimethoxybenzidine (DMOB) was rapidly metabolized in the rat. Thirty minutes after iv administration of 14C-DMOB, less than 2% of the dose could be recovered from the animal as the parent compound. Extensive biliary excretion (70% of the dose) resulted in the accumulation of approximately 50% of the dose in the intestinal tract. Three days after either oral or iv dosing, 50% of the administered radiolabel had been excreted in the feces and 30-40% excreted in the urine while 45% of the radiolabel remaining in the animal was present in the liver in the form of covalently bound metabolites. GC/MS studies of urine and bile demonstrated the presence of eight previously unidentified metabolites formed via N-acetylation, hydroxylation, O-demethylation, and glucuronidation. DMOB was mutagenic to Salmonella typhimurium strain TA98 only after metabolic activation by liver enzymes. N-Acetyl-DMOB was a more potent bacterial mutagen than either DMOB, N,N'-diacetyl-DMOB, or other biliary metabolites.

Autosomal recessive eye and brain anomalies: Warburg syndrome.

Two siblings are reported who appear to have an autosomal recessive disorder of eye and central nervous system anomalies. The findings in fourteen previously described and similarly affected patients are summarized. Ocular anomalies include microphthalmos, megalocornea, the Peter anomaly, cataract, coloboma, persistent hyperplastic primary vitreous, and retinal detachment with retinal dysplasia. Central nervous system malformations include agyria-pachygyria, cerebellar dysplasia, encephalocele, Dandy-Walker cyst, and hydrocephalus. We suggest that this disorder be known as Warburg syndrome.

Metabolism of the human carcinogen, benzidine, in the isolated perfused rat liver.

14C-Benzidine (BZ) was added to the recirculating perfusate of the isolated perfused rat liver. The system was monitored at timed intervals for the disappearance of BZ and the appearance of metabolites. BZ was extensively metabolized by this system and after 2 hr of perfusion greater than 95% of the administered radiolabel was in the form of metabolic products. In the perfusate the concentration of BZ declined rapidly whereas the concentration of N-acetyl-BZ (ABZ) increased temporarily and then declined. The concentration of N,N'-diacetyl-BZ (DABZ) increased with time and by 1 hr DABZ had become the major metabolite in the system. In the bile, which contained 22% of the dose after 2 hr, BZ-N-glucuronide and ABZ-glucuronide were the major metabolites initially, but after 1 hr of perfusion N-hydroxy-DABZ-glucuronide had become the major biliary metabolite. Addition of BZ and 35S-Na2SO4 to the perfusate resulted in at least one 35S-containing metabolite. Other major metabolites excreted in bile included 3-hydroxy-DABZ glucuronide, ABZ, and DABZ. DABZ underwent deacetylation to ABZ and N-hydroxy-DABZ underwent rapid reduction to DABZ when added to the isolated liver system. Qualitatively similar biliary metabolite patterns at later times were observed when either BZ, DABZ, or N-hydroxy-DABZ was added to the perfusate.

Invasive bladder carcinoma treated by radical cystectomy: survival of patients.

Sixty-three patients underwent radical cystectomy for invasive bladder carcinoma at West Virginia University Medical Center from 1961 to 1978. Survival statistics are presented and discussed in comparison with alternative modes of therapy. A brief discussion of complications is also presented.

Ureterosigmoidostomy followed by carcinoma of the colon.

Adenocarcinoma of the colon developing as a late complication or ureterosignoidostomy has been reported with increasing frequency. A patient is presented who developed adenocarcinoma of the colon 28 years after ureterosigmoidostomy for bladder exstrophy and 13 years after conversion of the ureterosigmoidostomy to an ileal conduit. The colonic tumor was documented at postmortem examination to be at the ureterosigmoidostomy site. Because of the potential late development of adenocarcinoma of the colon, careful follow-up of patients with ureterosigmoidostomies, particularly those performed in children many years ago, is indicated.