Clinical phenotyping in chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis: a management strategy for urologic chronic pelvic pain syndromes.

The urologic chronic pain conditions such as chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis are syndromes whose evaluation and management are controversial. Part of the difficulty in diagnosis and therapy is the heterogeneity of etiologies and symptoms. We propose a six-domain phenotype, which can classify these patients clinically and can direct the selection of therapy in the most evidence based multimodal manner. The domains are urinary, psychosocial, organ specific, infection, neurologic and tenderness of skeletal muscles. This system is flexible and responsive to new biomarkers and therapies as their utility and efficacy are proven.

Implantable FES system for upright mobility and bladder and bowel function for individuals with spinal cord injury.

STUDY DESIGN: Postintervention. OBJECTIVES: To determine the effectiveness of the Praxis multifunctional implantable functional electrical stimulation (FES) system (Neopraxis Pty. Ltd, Lane Cove, NSW, Australia) to provide standing and stepping ability and bladder and bowel management for individuals with motor complete thoracic level spinal cord injuries (SCI). SETTING: Pediatric orthopedic hospital specializing in SCI. SUBJECTS: Three males, ages 17 and 21 years, with motor-complete thoracic level SCI and intact lower motor neurons to the muscles targeted for stimulation. METHODS: Each subject was successfully implanted with the Praxis FES system. All three subjects received electrodes for upright mobility and the first two subjects received additional electrodes for stimulated bladder and bowel management. Following training, subjects were evaluated in their ability to use FES for nine mobility activities. Acute and chronic experiments of the effect of stimulation on bowel and bladder function were also performed. RESULTS: All three subjects could independently stand up from the wheelchair and could walk at least 6 m using a swing through gait pattern. Two subjects were able to independently perform swing through gait for 6 min and one subject was able to independently ascend and descend stairs. Suppression of reflex bladder contractions by neuromodulation (subject 1) and stimulated contractions of the rectum (subject 2) were observed in acute experiments. When stimulation was applied over the course of several weeks, a positive effect on bowel function was measured. Stimulated bladder contractions were not achieved. CONCLUSION: The feasibility of using the Praxis FES system for upright mobility and aiding aspects of bladder and bowel function was demonstrated with three subjects with thoracic level SCI.

A randomized placebo-controlled multicentre study to evaluate the safety and efficacy of finasteride for male chronic pelvic pain syndrome (category IIIA chronic nonbacterial prostatitis).

OBJECTIVE: To determine if finasteride can reduce symptoms in men with a clinical diagnosis of chronic nonbacterial prostatitis (National Institutes of Health, NIH, category IIIA chronic pelvic pain syndrome, CPPS) compared with placebo. PATIENTS AND METHODS: Men (76) with category IIIA CPPS enrolled in four North American prostatitis research centres were randomized after a 2-week placebo run-in to finasteride or placebo for 6 months. The primary efficacy variable was a subjective overall assessment (SOA); the secondary efficacy variables included the NIH chronic prostatitis symptom index (NIH-CPSI) and safety data. Patients were assessed at screening, baseline (after the 2-week placebo run-in), 3 and 6 months. RESULTS: Sixty-four patients had at least one assessment on medication (31 placebo, 33 finasteride); 75% of the finasteride and 54% of the placebo group had at least a mild improvement (defined as > 25% improvement in SOA), and 44% and 27%, respectively, a moderate or marked improvement (>50% improvement in SOA). The trend was similar in the NIH-CPSI scores. Five patients in the finasteride and seven in the placebo group reported medication-related adverse events. CONCLUSION: This randomized placebo-controlled pilot study suggests that finasteride was of benefit for some men with category IIIA CPPS, but the results do not justify recommending finasteride as monotherapy, except for men who also have benign prostatic hyperplasia. A larger, properly powered study, possibly evaluating combination with other therapies or specifically in men with prostatitis and benign prostatic hyperplasia, is required to confirm any clinical benefit.

The Spanish National Institutes of Health-Chronic Prostatitis Symptom Index: translation and linguistic validation.

PURPOSE: The prominence of health related quality of life end points in international clinical research underscores the importance of well validated and translated measures to enable cross-cultural comparison. The National Institutes of Health (NIH)-Chronic Prostatitis Symptom Index (CPSI) assesses symptoms and health related quality of life in men with chronic nonbacterial, NIH type III prostatitis. To expand its use to Spanish speaking patients we performed a translation and linguistic validation. MATERIALS AND METHODS: The 9-item NIH-CPSI was translated into Spanish according to a standard methodology of 2 forward translations, 1 reconciled version, back translation of the reconciled version and 3 independent reviews by bilingual experts. The purpose of this methodology was to create a single universal Spanish version that would be acceptable to native Spanish speakers inside and outside of the United States. After the translation process the Spanish version was pre-tested in Argentina, Mexico, Spain and the United States. Patient responses were analyzed to identify necessary modifications. The internal consistency of the CPSI was evaluated using Cronbach's alpha. Pearson's product moment correlations were used to evaluate construct validity. RESULTS: Data were collected from chronic prostatitis patients, including 15 in Argentina, 15 in Mexico, 4 in the United States and 3 in Spain. The translation had high reliability overall and in all subscales (Cronbach's coefficient alpha = 0.81 to 0.94), and the subscales correlated well with each other (r = 0.76 to 0.97). However, patients expressed difficulty in distinguishing the response categories "a menudo" ("often") from "normalmente" ("usually") in question 3. We revised "a menudo" to "muchas veces" ("much of the time") and "normalmente" to "casi siempre" ("almost always") to improve the distinctiveness of response categories. CONCLUSIONS: The Spanish NIH-CPSI has high reliability as well as face and construct validity in Spanish speaking men from various countries. The Spanish NIH-CPSI permits cross-cultural comparisons of men with chronic nonbacterial prostatitis.

Quality of life is impaired in men with chronic prostatitis: the Chronic Prostatitis Collaborative Research Network.

OBJECTIVE: Health-related quality of life (HRQOL) impairment may be a central component of chronic prostatitis for men afflicted with this condition. Our objective was to examine HRQOL, and factors associated with HRQOL, using both general and condition-specific instruments. DESIGN: Chronic Prostatitis Cohort (CPC) study. SETTING: Six clinical research centers across the United States and Canada. PARTICIPANTS: Two hundred seventy-eight men with chronic prostatitis. MEASUREMENTS AND MAIN RESULTS: The Short Form 12 (SF-12) Mental Component Summary (MCS) and Physical Component Summary (PCS), and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) were measures used. CPC subjects' MCS scores (44.0 +/- 9.8) were lower than those observed in the most severe subgroups of patients with congestive heart failure and diabetes mellitus, and PCS scores (46.4+/-9.5) were worse than those among the general U.S. male population. Decreasing scores were seen in both domains with worsening symptom severity (P < .01). History of psychiatric disease and younger age were strongly associated with worse MCS scores, whereas history of rheumatologic disease was associated with worse PCS scores. Predictors of more severe NIH-CPSI scores included lower educational level and lower income; history of rheumatic disease was associated with higher scores. CONCLUSIONS: Men with chronic prostatitis experience impairment in the mental and physical domains of general HRQOL, as well as condition-specific HRQOL. To optimize the care of men with this condition, clinicians should consider administering HRQOL instruments to their patients to better understand the impact of the condition on patients' lives.

Comparison of bladder blood flow in patients with and without interstitial cystitis.

PURPOSE: We compared bladder blood flow during filling and emptying in patients with and without interstitial cystitis, and correlated blood flow with symptoms in those with interstitial cystitis. MATERIALS AND METHODS: Bladder perfusion was measured using a dual channel endoscopic laser Doppler flow probe. Measurements were obtained in superficial and deeper vascular beds from the bladder mucosa at the trigone and back wall at baseline, at the volume of awake capacity, during 80 cm. water hydrodistention and after bladder drainage. American Urological Association symptom score was obtained preoperatively in interstitial cystitis patients. RESULTS: In all areas bladder perfusion decreased with filling in interstitial cystitis patients and increased in those without interstitial cystitis. There were no significant differences in response to emptying the bladder, as perfusion tended to increase in both groups. There was no correlation between bladder perfusion at baseline, or in response to filling or emptying with overall symptom score. CONCLUSIONS: Bladder perfusion decreases with bladder filling in patients with but increases in those without interstitial cystitis. The inability of the interstitial cystitis bladder to increase bladder blood flow with filling may be a reflection of other pathological processes in the bladder mucosa. The lack of correlation between blood flow and symptoms suggests that bladder ischemia alone cannot account for the symptoms in interstitial cystitis.

The National Institutes of Health chronic prostatitis symptom index: development and validation of a new outcome measure. Chronic Prostatitis Collaborative Research Network.

PURPOSE: Chronic abacterial prostatitis is a syndrome characterized by pelvic pain and voiding symptoms, which is poorly defined, poorly understood, poorly treated and bothersome. Research and clinical efforts to help men with this syndrome have been hampered by the absence of a widely accepted, reliable and valid instrument to measure symptoms and quality of life impact. We developed a psychometrically valid index of symptoms and quality of life impact for men with chronic prostatitis. MATERIALS AND METHODS: We conducted a structured literature review of previous work to provide a foundation for the new instrument. We then conducted a series of focus groups comprising chronic prostatitis patients at 4 centers in North America, in which we identified the most important symptoms and effects of the condition. The results were used to create an initial draft of 55 questions that were used for formal cognitive testing on chronic prostatitis patients at the same centers. After expert panel review formal validation testing of a revised 21-item draft was performed in a diverse group of chronic prostatitis patients and 2 control groups of benign prostatic hyperplasia patients and healthy men. Based on this validation study, the index was finalized. RESULTS: Analysis yielded an index of 9 items that address 3 different aspects of the chronic prostatitis experience. The primary component was pain, which we captured in 4 items focused on location, severity and frequency. Urinary function, another important component of symptoms, was captured in 2 items (1 irritative and 1 obstructive). Quality of life impact was captured with 3 items about the effect of symptoms on daily activities. The 9 items had high test-retest reliability (r = 0.83 to 0.93) and internal consistency (alpha = 0.86 to 0.91). All but the urinary items discriminated well between men with and without chronic prostatitis. CONCLUSIONS: The National Institutes of Health chronic prostatitis symptom index provides a valid outcome measure for men with chronic prostatitis. The index is psychometrically robust, easily self-administered and highly discriminative. It was formally developed and psychometrically validated, and may be useful in clinical practice as well as research protocols.

Sex differences and role of nitric oxide in blood flow of canine urinary bladder.

Continuous measurements were made of bladder blood flow by laser Doppler flowmetry in anesthetized dogs during bladder filling and emptying. In both mucosa and muscle, perfusion was inversely proportional to intravesical pressure. There was significantly greater perfusion in the bladder mucosa of males than females at baseline and up to 10 cm water filling pressure but not in the muscle. Intra-arterial infusion of the nitric oxide synthase inhibitor NG-nitro-L-arginine produced a significant decrease in resting bladder perfusion in the mucosa only, with no differences seen in the response to intravesical pressure. Intra-arterial infusion of L-arginine produced a significant increase in the level of perfusion in the mucosa seen immediately after the bladder was drained. No changes were observed in muscle perfusion after L-arginine. These results suggest that the perfusion of the bladder mucosa differs by gender and is regulated differently than the bladder muscle, possibly related to the different function of the two layers.

Adverse urologic consequences of spinal cord resection at the time of kyphectomy: value of preoperative urodynamic evaluation.

Four children with thoracic level paraplegia and severe myelokyphosis underwent distal spinal cord resection at the time of kyphectomy. All four children were continent before spinal cord resection and became incontinent immediately afterward. Two children in retrospect had preoperative urodynamics that showed intact innervation to the external sphincter, and two had no preoperative urodynamic studies. All four had evidence of lower urinary tract denervation on urodynamic studies performed after cord resection. The urologic and urodynamic consequences of spinal cord resection at the time of kyphectomy in children with myelodysplasia are reviewed. Resection of the distal spinal cord in thoracic level myelodysplasia may cause postoperative incontinence in some previously continent patients. Preoperative urodynamic evaluation and urologic consultation is recommended. If individual evaluation indicates that residual sacral function is beneficial to urologic management, kyphectomy without cord resection is preferable.

Characterization of muscarinic cholinergic receptor subtypes in rat prostate.

The purpose of this study was to characterize the muscarinic receptor subtypes in the individual lobes of the rat prostate. Immunoprecipitation was performed on homogenates of these 3 lobes using antibodies to the m1-m4 muscarinic receptor subtypes. Reverse transcriptase polymerase chain reaction assays (RT-PCR) were also performed using primers specific for each of the five muscarinic receptor subtypes (m1-m5). The susceptibility of the receptors to degradation by endogenous prostate proteases was assessed by mixing rat ventral prostate with rat heart (m2) and rat parotid (m3) prior to immunoprecipitation. In the ventral lobe, transcripts for the m1-m4 subtypes were amplified whereas in the dorsal and lateral lobes only the m2 and m3 sets of primers amplified PCR products of the predicted size. Immunoprecipitation of the ventral lobe resulted in predominantly m3 receptors, while the majority of receptors immunoprecipitated from lateral and dorsal lobes were the m2 subtype. The m3 muscarinic subtype was apparently susceptible to degradation by prostate proteases whereas the m2 subtype was not. These results demonstrate a regional distribution in the subtypes of muscarinic receptors in the rat prostate, and a greater susceptibility of the m3 receptor to degradation during immunoprecipitation than the m2 subtype.

Logical and systematic approach to the evaluation and management of patients suspected of having interstitial cystitis.

OBJECTIVES: To outline a systematic approach to the evaluation, diagnosis and treatment of interstitial cystitis (IC). METHODS: A review of the literature as well as of our experience. RESULTS: The exclusion criteria for the research definition of IC can be used as guides when obtaining the history, physical examination, laboratory workup, and finally urodynamics and cystoscopy/hydrodistension under anesthesia. Once the diagnosis is established, patients who are still symptomatic after hydrodistension are treated initially with oral medications. Those who do not respond to oral therapy are given intravesical therapy. Patients whose symptoms are refractory to both routes can be considered for a TENS unit, experimental oral therapies, chronic pain control with opioids, or, as a last resort, surgery to create a urinary diversion. CONCLUSION: As IC is a diagnosis of exclusion, the evaluation remains one of ruling out other disorders that produce similar symptoms in patients whose history suggests IC. Until the etiology and pathogenesis of IC are identified, specific therapy is not possible. However, symptomatic treatments are helpful in the majority of patients.

Human prostate muscarinic receptor subtypes.

The alpha adrenergic receptor subtypes of the human prostate have been intensively investigated, while the muscarinic receptor subtypes and their function have yet to be determined in this tissue. [3H]-QNB binding to muscarinic receptors was performed on membrane homogenates of adenoma from six prostatectomy specimens resulting in an average total receptor density of 46 fMol/mg protein. Pirenzepine, hexahydrosiladifenidol, and para-fluoro-hexahydrosiladifenidol, drugs with high affinity for the M1 subtype, were significantly more potent inhibitors of [3H]-QNB binding than the M2 selective drug methoctramine. Immunoprecipitation studies were done using antisera raised to individual M1-M5 receptor subtypes. Approximately 75% of the solubilized receptors in the adenoma specimens were immunoprecipitated with the anti-M1 antibody, in contrast to 5% or less with antibodies against M2, M3 or M4 subtypes. These immunoprecipitation studies confirm the preponderance of the M1 subtype in prostate adenoma suggested by the high affinity pirenzepine binding. M1 receptors, when incubated with agonist, coimmunoprecipitated with the alpha subunits of the guanine nucleotide binding regulatory proteins Gi alpha, Gq/11 alpha and G16 alpha. Immunohistochemical staining with the anti-M1 antibody demonstrates the M1 receptor to be localized to the glandular epithelium. The human prostate is the first peripheral tissue in which a preponderance of the M1 subtype of muscarinic receptors has been demonstrated.

Retained sacral function in children with high level myelodysplasia.

To assess the preservation of sacral function despite denervation higher on the spinal cord in children with myelodysplasia, we examined 151 myelomeningocele patients presenting for urodynamic evaluation from 1980 to 1992 with a lesion at L3 or above on neurological examination. Of the 151 patients 70 (46%) had denervation of the external sphincter on initial evaluation and 81 (54%) had sacral sparing, that is normal or near normal electrical potentials of the external urethral sphincter and/or retained reflexic bladder activity regardless of the presence or absence of sacral reflexes. Of the 81 patients with sacral sparing 57 (70%) had detrusor-sphincter dyssynergia and 21 had synergy or denervation of the sphincter in association with retained detrusor reflexia. Whereas only 18% of children age 1 year or younger with retained sacral function had upper urinary tract deterioration on initial radiological studies (manifested by reflux or hydronephrosis), 57% had deterioration when evaluated after age 1 year. None of the patients without retained sacral function had evidence of upper urinary tract damage at younger than 1 year but 28% of those studied beyond age 1 year had changes. Patients with flaccid lower extremities can retain sacral function, which puts the upper urinary tract at risk of deterioration. Our results show that this risk increases with time.

Diagnosis and treatment of enterovesical fistulae.

Presenting symptoms, diagnostic progression, etiology, therapy, and complications of 44 patients with enterovesical fistulae who came to three Yale teaching hospitals over a 9-year period were reviewed. Patients with diverticulitis as the cause of their fistula were older and came to the hospital with pneumaturia/fecaluria. Patients with pelvic cancer were more likely to have fecaluria, gastrointestinal symptoms, or hematuria. Patients with Crohn's disease were an average of 20 years younger than the patients with cancer or diverticulitis and they came to the hospital with pneumaturia, abdominal pain, abdominal mass, and tenderness. Computerized axial tomography scanning, cystoscopy, charcoaluria, and barium enema were useful in making the diagnosis; intravenous pyelography and colonoscopy were not. One-tenth of the patients were not candidates for operation, and one-quarter of the patients did not undergo complete operative resolution with restoration of enteric and urinary continuity. Nine patients underwent a two-stage repair consisting of resection/repair of the fistula with proximal fecal diversion and subsequent re-establishment of bowel continuity. These patients had a higher morbidity than the 19 patients who underwent one-stage repair. Enterovesical fistula is a challenging entity, the etiology of which may be suspected upon taking the patient's history or performing the physical assessment; however, the definitive diagnosis of enterovesical fistula can remain elusive. Single-stage repair can be achieved with low morbidity and mortality in many candidates.

The straight radial-antecubital PTFE angio-access graft in an era of high-flux dialysis.

Straight radial-antecubital polytetrafluoroethylene (PTFE) grafts were placed in 10 older (greater than 55 years) male patients with significant intercurrent diseases who were considered candidates for high-flux dialysis. Graft patency was 90% at 6 months, and suitable flow for high-flux dialysis (greater than 400 mL/minute) could be achieved with all grafts. Shorter dialysis times with no major cardiovascular, hemodynamic, or extremity complications were achieved with this mode of therapy. The principles and practicalities of high-flux dialysis are reviewed. This small series of patients demonstrates that the relatively low resting flow of the straight radial-antecubital PTFE graft should not be a major consideration in the choice of this vascular access procedure in patients being considered for high-flux dialysis. Straight radial-antecubital PTFE grafts preserved both the ulnar collateral to the hand and the brachial artery for later access, yet provided adequate flow in all patients in whom they remained patent.