Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness.

PURPOSE: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. RESULTS: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. CONCLUSIONS: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

Hepatic decompensation in patients with cirrhosis during infection with influenza A.

BACKGROUND: Patients with chronic liver disease can develop hepatic decompensation during systemic infections. Although gram-negative and gram-positive bacteria are well recognized as causes of decompensation, the effect of influenza virus infection on patients with chronic liver disease is poorly documented. METHODS: Retrospective analysis of patients with positive viral cultures who were seen at a liver transplantation clinic in a tertiary care referral center during the 1997-1998 influenza A (H3N2) epidemic in San Diego, Calif. RESULTS: Three patients with end-stage liver disease (1 with Wilson disease and 2 with alcoholic liver disease) developed hepatic decompensation and required hospitalization during infection with influenza A. Two patients had biochemical and clinical evidence of hepatic decompensation, including ascites, hepatic encephalopathy, and peripheral edema, and the third had acute hepatocellular damage, with elevated levels of aminotransferases. Viral hepatitis serologic test results, acetaminophen levels, drug and alcohol screening findings, and bacterial and fungal cultures were negative in all 3 patients. Hepatic decompensation resolved without the need for transplantation in the 2 patients with liver failure, and all patients recovered to their baseline liver function levels within 1 month of onset of acute illness. CONCLUSIONS: Influenza A infection can cause hepatic decompensation and hospitalization in patients having cirrhosis or who are awaiting liver transplantation. Effective prevention with vaccination and early recognition and treatment of influenza are strongly recommended in these individuals.

The ontogeny of the androgen receptor in human foreskin.

To investigate the relationship between the androgen receptor content of human foreskin and age-dependent physiological changes in genital development, cytosolic and nuclear androgen receptors were measured in preputial skin specimens from male subjects of various ages. Optimum incubation conditions (4 C, 20 h) were established for measurement of androgen receptors by the exchange method with the synthetic androgen ligand methyltrienolone. The number of total androgen receptor sites, cytosolic plus nuclear, was fairly constant at all ages studied. However, the androgen receptor was predominantly localized to the nuclear compartment at those developmental stages characterized by higher levels of circulating blood androgens, i.e. newborns, pubertal males, and adults. By contrast, the androgen receptor in specimens from prepubertal boys was confined almost exclusively to the cytosolic compartment. This corresponds to a time of low plasma androgen levels and quiescence in genital maturation. It is suggested that changes in the intracellular distribution of androgen receptors may bear some relationship to the sequence of normal genital growth and development with nuclear androgen receptors having major physiological importance.

Peyronie's disease: a newly recognized autosomal-dominant trait.

Peyronie's disease, a connective tissue disorder of unknown cause, is characterized by the formation of thickened fibrous plaques on the dorsum of the penis. It often occurs simultaneously with other fibrotic changes, most notably Dupuytren's contracture of the hands or feet. There are no previous reports suggesting inheritance of this syndrome; however, Willscher et al reported an association between Peyronie's disease and antigens of the HLA-B7 cross-reacting group. Family studies were undertaken when three patients reported similarly affected first-degree relatives. One kindred showed father-to-son transmission of Peyronie's disease with Dupuytren's contracture in three generations. Pedigree analysis of the three families suggests that Peyronie's syndrome is a male-limited, autosomal-dominant trait. Antigens of the HLA-B7 cross-reacting group occurred in all three kindreds; however, the data ruled out close linkage of the disease and HLA.

Perinephric and intrarenal abscesses.

Perinephric and intrarenal abscesses remain a significant source of morbidity and mortality as well as a diagnostic dilemma. The history, epidemiology, disease classification, etiology, diagnosis, and treatment are reviewed, with special attention to new diagnostic and treatment modalities.

The Interstitial Cystitis Data Base Study: concepts and preliminary baseline descriptive statistics.

OBJECTIVES: To describe the design, patient population, and data and specimen collection aspects of the interstitial Cystitis Data Base (ICDB) Study and to provide preliminary descriptive statistics and inferential results from an interim analysis. METHODS: All 424 study participants successfully enrolled in the ICDB Study prior to December 31, 1995, were selected for an interim analysis and were classified into 1 of 3 symptom severity subgroups. Statistical tests for associations among these symptom severity subgroups and a broad range of baseline characteristics were conducted using Mantal-Haenszel procedures to adjust for variation among clinical centers. RESULTS: ICDB Study patients are predominantly female (91.5%), white (91.0%), with an average age at enrollment of 44.3 years. Nearly 45% of these patients underwent a cystoscopy at baseline screening, among whom there was an overall prevalence of 10.5% for Hunner's patch and 90% for glomerulations. Urodynamic evaluation for the entire 424 patients demonstrated that volumes at first sensation and at maximal capacity were inversely associated with symptom severity subgroups. A broad range of symptoms were analyzed, indicating that nearly 40% of patients reported urinating 15 times or more during awake hours, and more than 20% reported voiding at least 4 times per night. Almost half (47.9%) reported constant urgency and 23.6% reported having severe pain. Patients in the severe symptom subgroup reported greater limitations in selected quality-of-life indicators than those with less severe symptoms. CONCLUSIONS: This interim analysis of the ICDB Study data was compared to previous epidemiologic studies of IC and provides an essential foundation for further analytic investigations of baseline associations and longitudinal trends.

Associations among urodynamic findings and symptoms in women enrolled in the Interstitial Cystitis Data Base (ICDB) Study.

OBJECTIVES: The goal of this study was to correlate the cystometric findings with the presenting symptoms of the 388 women enrolled in the NIH/NIDDK-funded interstitial Cystitis Data Base (ICDB) Study as of December 31, 1995. METHODS: All patients underwent a complete history and physical and completed standardized questionnaires to assess voiding symptoms and quality of life (QOL). A 3-day voiding log was also obtained, followed by a baseline urodynamic exam. All results are expressed as mean values +/- 1 standard deviation, and all reported correlations were significant. RESULTS: A correlation was seen between reported daytime, nighttime, and 24-hour frequency, and both volume at first sensation to void (VFSV) and maximal cystometric capacity (VMCC). Patients with constant severe urgency had smaller VFSV, 63 +/- 59 mL versus 108 +/- 90 mL, and lower VMCC, 163 +/- 102 mL versus 288 +/- 135 mL, than patients without the complaint. A negative trend was seen for both VFSV and VMCC versus the global severity. An inverse trend was seen between minimal and maximal pain scores over the 4 weeks before the exam and VMCC. (No correlation existed between current pain noted during baseline screening visits and VFSV or VMCC). No urodynamics correlates were seen with global measures of body pain and global health. Uninhibited detrusor contractions (UDCs) were seen in 56 of 384 patients (14.6%). A positive correlation was seen between urgency symptoms and the presence of UDCs. Correlations between the VFSV and VMCC were made with both the average voided volume (AVV) and the average maximal voided volume (AMVV) as determined by a 3-day voiding log. Significant positive correlations were seen with each pair-wise comparison (P = 0.001). CONCLUSION: These findings confirm that subjective measurements of symptoms associated with interstitial cystitis can be confirmed objectively with urodynamic studies.

Associations among cystoscopic findings and symptoms and physical examination findings in women enrolled in the Interstitial Cystitis Data Base (ICDB) Study.

OBJECTIVES: To determine if specific symptoms or physical findings were associated with findings on cystoscopic examination under anesthesia in patients participating in the Interstitial Cystitis Data Base (ICDB) Study. METHODS: Subjects entering the ICDB Study completed symptom questionnaires and underwent physical examinations. Additionally, at the discretion of study investigators, 150 women underwent cystoscopy under anesthesia following a specific protocol of bladder distension at 70 to 80 cm irrigating fluid height and reinspection after capacity was reached and the irrigant drained. RESULTS: Statistically significant (p < 0.01) associations between bodily pain and urinary urgency with the presence of a Hunner's patch, and urinary frequency and urgency with a reduced bladder capacity under anesthesia were seen. Neither the findings of bloody irrigating fluid nor glomerulations were strongly associated with any symptom, and except for an association of urethral tenderness with Hunner's patch, no physical examination finding was associated with any cystoscopic findings. CONCLUSIONS: The strong associations of Hunner's patch and reduced bladder capacity under anesthesia with severe pain and urinary urgency, and urgency and frequency, respectively, indicate not only the importance of these findings in diagnosing interstitial cystitis, but also their potential utility in subclassifying this disease.

Associations among cystoscopic and urodynamic findings for women enrolled in the Interstitial Cystitis Data Base (ICDB) Study.

OBJECTIVES: Interstitial cystitis is a symptom complex characterized by pelvic pain, urinary urgency, urinary frequency, and nocturia. Patients with these symptoms, at the 5 clinical centers participating in the National Interstitial Cystitis Data Base (ICDB) Study, have been evaluated with history and physical exams, questionnaires, and urodynamic studies. METHODS: Of the 388 female subjects entered in the study as of December 31, 1995, 150 women have undergone cystoscopy with hydrodistension. The data from the endoscopic procedures and the urodynamic studies were analyzed. The associations among cystoscopic and urodynamic findings were reviewed. RESULTS: Patient demographics of this subgroup show a predominance of Caucasians 139/150 (92.7%), with the average age being 43 (+/-13.2) years. Of the total, 17 patients (11.3%) had a Hunner's patch (HP). The prevalence by center varied from a low of 2/38 (5.3%) to a high of 3/9 (33.3%). Bloody effluent following hydrodistension was present in 113/150 (75.3%). Glomerulations appeared in varying degrees (mild, moderate, severe) in 91.3% of the 150 patients. There was a strong inverse relationship (P < 0.001) between bladder capacity under anesthesia and the presence of a HP (mean of 845 cc with HP absent versus a mean of 531 cc when present). The incidence of HP varied from 67.6% among women with a bladder capacity at hydrodistension of < 400 cc to 3.8% for those with a bladder capacity of at least 800 cc. The presence and increasing severity of glomerulations was positively associated (P < 0.003) with the presence of HP, ranging from 0/13 (0%) when glomerulations were not present to 6/31 (19.4%) when glomerulations were graded as severe. Of the patients with HP, 17/17 (100%) had glomerulations after hydrodistension. HP is more closely associated with the moderate to severe range of glomerulations (P < 0.01). Nearly half of the patients with HP or 8/17 (47.1%) had "moderate" glomerulations, while 6/17 (35.3%) had "severe" glomerulations. The volume at first sensation to void on urodynamics (mean 87 cc without HP versus 34.7 cc with HP) was highly inversely associated (P = 0.002) with the presence of HP, but not with any of the other cystoscopic findings. Of patients with HP, 94% had a volume at first sensation to void of < or = 50 cc where only 36% of patients without HP had a volume at first sensation to void of < or = 50 cc. The volume at maximum capacity on urodynamics was positively associated with the volume at hydrodistension (P < 0.001). CONCLUSIONS: Overall, patients with HP had lower bladder capacities, lower volumes at first sensation to void, and more severe glomerulations. Thus, the presence of HP would imply a more severe case of interstitial cystitis. Logically, a higher bladder capacity on cystometrogram is associated with a higher volume at the time of hydrodistension, and bloody effluent is associated with more severe glomerulations.

Suppression of post-vasectomy cytotoxic sperm antibody formation in rats by a short-term pretreatment with cyclosporine.

The effect of a short pulse therapy with cyclosporine on the production of vasectomy-induced cytotoxic sperm antibodies was studied in Lewis rats. Cyclosporine at a dose of 10 mg/kg was administered once daily for 7 days before and 7 days after vasectomy (group A), for 7 days before vasectomy (group B), and for 7 days after vasectomy (group C). Ten rats were studied in each group for a period of 5 weeks. Ten rats were vasectomized and untreated with cyclosporine (group U). All animals in this group developed high titers of cytotoxic sperm antibodies at the end of the first week after vasectomy (primary antibody response). In contrast, all the treated rats of groups A, B, and C had a normal range of sperm antibody titers. By the third week, six of nine rats in the post-treated group C had significant cytotoxic sperm antibody titers, while the other groups had normal antibody titers. In the fourth week, all the rats of groups A and B continued to have normal sperm antibody titers of less than or equal to 16, while most animals in groups C (78%) and U (63%) had significant cytotoxic sperm antibody titers. It is concluded that prevasectomy treatment with cyclosporine may significantly reduce or delay the production of cytotoxic sperm antibodies in Lewis rats.

Pathological and immunological effects of surgically induced varicocele in juvenile and adult rats.

The presence of a varicocele in adult men has been correlated with infertility. This study documents the effect of an experimentally induced unilateral varicocele in 21-day-old juvenile prepubertal and 51-day-old adult rats (n = 10 per group) on subsequent adult testicular function. Varicoceles were induced by partial occlusion of the spermatic vein. There were ten sham-operated and five nonoperated control rats in each age group. The rats were sacrificed 1 month after surgery. Intrascrotal temperatures were elevated in both groups with varicoceles. Histologically, the ipsilateral testes of rats in both age groups demonstrated a decrease in the numbers of functioning seminiferous tubules and germ cells, but the decrease was significantly greater in the juveniles than in the adult rats. No changes were seen in the contralateral testes. Significant titers of cytotoxic sperm antibodies were present in all animals with varicoceles, which is in contrast to controls. The juveniles had significantly lower antibody titers (mean log2 +/- SEM; 3.2 +/- 0.09 vs. 8.5 +/- 1.1, P less than 0.001) than the adults. The induction of a unilateral varicocele damaged spermatogenesis and testicular function to a greater extent in juveniles than in adult rats. This damage may be immune complex-mediated.

Funding for urolithiasis research: progress and strategies for future NIH support.

A review of the National Institutes of Health funding history for urolithiasis shows that support has increased from about $3 million in 1990 to about $4.7 million in 1993 and to an estimated $5.1 million in 1994. The award of large project grants accounts for the increase: individual research project grant funding (R01-type grants) has not increased. The overall funding for urologic research supported by the National Institute of Diabetes and Digestive and Kidney Diseases has more than doubled in this same period, with most of the increase attributable to the award of individual research grants. Although there has been a significant number of urolithiasis research grant applications submitted in this time period, the percent of successful (funded) applications continues to lag behind the number in other urology-related areas. Strategies for improving the award rate for urolithiasis-related research grant applications are reviewed.

Organ culture of osteopetrotic (ia) rat bone: evidence that the defect is cellular.

Calvarial bone from osteopetrotic (ia) rats and normal littermates has been cultured in a chemically defined medium supplemented with homologous serum to test for the presence of inhibitors or the absence of promoters of bone resorption in mutant serum. In addition, the response of mutant and normal bone to parathyroid extract and hydrocortisone was tested in vitro. The results indicate that mutant and normal serum do not differ with respect to their ability to support bone resorption and that ia bone responds to hydrocortisone but not parathyroid extract in organ culture. These data indicate that the skeletal defect in ia rats is not humoral but cellular.

Genitourinary fungal infections.

Genitourinary fungal infections have become increasingly common in clinical practice. We review the literature on such infections, emphasizing recognition of fungal disease, predisposing factors, pathogenesis, and approaches to therapy.

The epidemiology of interstitial cystitis: is it time to expand our definition?

Very few epidemiologic studies of interstitial cystitis (IC) have been published over the past 5 years. One population-based study focused only on women and suggested that the prevalence of the IC symptom complex in the United States is much higher than previously reported. Future epidemiologic studies of IC must overcome major obstacles to obtain more accurate population-based estimates. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) criteria used to assist in identifying patients with IC have proven to be cumbersome and too restrictive. Other obstacles include (1) the relative infrequency of the condition; (2) the long duration between development of symptoms and diagnosis; and (3) the perception that the disorder occurs predominantly in white women. Evidence suggests men with the IC symptom complex are often misdiagnosed by physicians and identified as having chronic prostatitis (also called the chronic pelvic pain syndrome) or benign prostatic hyperplasia. Children who present with the IC symptom complex are often thought to have voiding dysfunction. We propose that the more inclusive, less restrictive term chronic pelvic pain of the bladder (CPPB) be used in future epidemiologic studies of persons with the characteristic IC symptoms of urinary frequency, urgency, and pain. Early studies of chronic pelvic pain in general suggest that it is most common in women, of unknown etiology, and, in many patients, is associated with urinary bladder symptoms. It is necessary to develop case definitions for CPPB to accurately identify those patients with symptoms currently identified as IC.

Research guidelines for chronic prostatitis: consensus report from the first National Institutes of Health International Prostatitis Collaborative Network.

OBJECTIVES: The National Institutes of Health (NIH) organized the first International Prostatitis Collaborative Network workshop (November 5 and 6, 1998, Washington, DC) to address the confusion surrounding the diagnostic and treatment strategies in chronic prostatitis. METHODS: A panel of North American and international urologic researchers, interested physicians, medical industry representatives, and patients were invited to participate and reviewed current definitions, classification systems, and recent epidemiologic and both published and "in progress" treatment studies. RESULTS: A general concensus was developed for adoption of the following criteria for clinical studies in chronic prostatitis/chronic pelvic pain syndrome: (a) the NIH definition of chronic prostatitis/chronic pelvic pain syndrome; (b) the 1995 NIH Classification System; (c) the eligibility (inclusion/exclusion) criteria developed by the NIH Chronic Prostatitis Clinical Research Network; (d) the NIH Chronic Prostatitis Symptom Index. It was agreed that clinical treatment trials involving presently available, experimental, and theoretical therapeutic modalities be prioritized according to maximum potential benefits and that regulatory authorities (ie, Food and Drug Administration in the United States) consider major changes in the approval process for treatment modalities in chronic prostatitis. CONCLUSIONS: Chronic prostatitis is a major health care issue. Standardization of definitions, classification, study design, and outcome parameters will promote rational and comparative evaluation of diagnostic and therapeutic strategies.

Overview of past and current philosophy of prostatic cancer.

Carcinoma of the prostate is the second most common cancer in men, yet no significant change in overall survival has occurred since the original description of the results of castration by Huggins and Hodges. Many important questions about the disease remain unanswered. The cause of prostatic cancer is unknown, and few specific environmental or viral agents have been linked with the tumor. Increased recognition of the importance of frequent digitial rectal examination has resulted in more tumors being diagnosed in early stages. Developments in sonography suggest that it may be useful in detecting the presence of prostatic cancer and whether extraprostatic extension has occurred. Recent inprovements in the sensitivity of prostatic acid phosphatase assays have been made, but their use as a screening tool remains limited. In patients with clinical stage B lesions that are microscopically confined to the prostate, treatment by radical prostatectomy appears to confer greatest survival. The exact role of radiotherapy remains to be defined. However, when the tumor extends beyond the prostate and is localized to the pelvis, external beam ro interstitial radiation is appropriate. Pelvic lymphadenectomy has significant morbidity, but less invasive methods of pelvic nodal evaluation are less accurate. Lymphadenectomy has not been shown to have any therapeutic effect. Whether hormonal therapy improves survival needs further investigation, and efforts must continue to develop means of predicting hormonal responsiveness. Those patients unlikely to respond to hormonal therapy should be treated with early chemotherapy.