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.

A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis.

PURPOSE: This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial. MATERIALS AND METHODS: A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine. Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months. RESULTS: A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports. CONCLUSIONS: The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.

Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study.

The purpose of this study was to investigate associations between bladder biopsy features and urinary symptoms for patients enrolled in the Interstitial Cystitis Database (ICDB) Study. Bladder biopsies were obtained during baseline screening in the ICDB Study and were evaluated for histopathologic features. Multivariable models for nighttime voiding frequency, urinary urgency, and pain were developed, incorporating biopsy features from the most diseased area of the bladder as predictors, adjusting for significant clinical factors, and clinical center variation. Among 204 interstitial cystitis (IC) patients providing biopsy specimens, cystoscopic pathology findings were not statistically associated (P >0.1) with primary IC symptoms, although the presence of Hunner's ulcer (n = 12) was suggestive of increased urinary frequency. Within a multivariable predictive model for nighttime voiding frequency, adjusting for age and minimum volume per void, 4 pathology features were noted: (1) mast cell count in lamina propria on tryptase stain; (2) complete loss of urothelium; (3) granulation tissue in lamina propria; and (4) vascular density in lamina propria on factor VIII (F8) stain were statistically significant (P <0.01). Similarly, in a multivariable model for urinary urgency, minimum volume, and percentage of submucosal granulation tissue remained statistically significant (P <0.01). Finally, the percentage of mucosa denuded of urothelium and the percentage of submucosal hemorrhage remained highly associated (P <0.01) with pain in a multivariable predictive model. The fact that the presence or severity of glomerulations was not selected for any of these predictive models suggests that cystoscopic findings of glomerulations are not predictive of IC symptoms. Furthermore, these results suggest an important role for certain pathologic features in the predictive modeling of IC symptoms.

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.

Immune response to influenza vaccine in adult liver transplant recipients.

Influenza virus infection may cause significant complications in liver transplant recipients, and whether vaccination is effective in these patients is controversial. We performed a study to assess the immune response to influenza vaccine in liver transplant recipients and patients with cirrhosis compared with healthy controls. Liver transplant recipients (n = 20), patients with compensated cirrhosis awaiting transplantation (n = 14), and healthy volunteers (n = 9) were administered the standard dose of the 1999 to 2000 inactivated trivalent vaccine (A/Bejing/262/95[H1N1]; A/Sidney/5/97[H3N2]; B/Yamanashi/166/98). Antibody responses to each component of the vaccine were measured at baseline and after 6 weeks by hemagglutination inhibition. Vaccination was well tolerated, and no major side effects were observed. A significant postvaccination increase in antibody titer to all 3 vaccine components was obtained in all groups. However, liver transplant recipients had significantly lower postvaccination geometric mean titers and geometric mean increases to the H3N2 component compared with patients with cirrhosis and controls. The rate of seroconversion to H3N2 after vaccination was also significantly lower in liver transplant recipients (15% v. 89%). We conclude that liver transplant recipients have a significantly impaired immune response to the influenza vaccine, and some patients may remain unprotected from influenza infection after vaccination. Further studies of modified protocols of influenza vaccination for these patients are recommended.

Treatments used in women with interstitial cystitis: the interstitial cystitis data base (ICDB) study experience. The Interstitial Cystitis Data Base Study Group.

OBJECTIVES: To evaluate the frequency and types of treatments reported at baseline in women who entered the Interstitial Cystitis Data Base (ICDB) cohort study. METHODS: From 1993 to 1997, 581 women were enrolled and followed in the ICDB. All treatments reported at study entry, including those prescribed for interstitial cystitis (IC) and concomitant medications, were reviewed. The number and types of treatments were evaluated with respect to baseline factors such as prior diagnosis of IC and symptom severity. RESULTS: One hundred five (18%) women were receiving no therapy at baseline. Single-mode therapy was reported by 195 (34%) women, and a combination of two treatments was reported by 119 (21%) women. Three or more treatments were reported in 162 (28%) women. A total of 183 different types of therapies were recorded. The five most commonly used therapies for IC symptoms were cystoscopy and hydrodistention, amitriptyline, phenazopyridine, special diet, and intravesical heparin. Because most patients entered the ICDB before the approval of oral pentosan polysulfate sodium (PPS), only 6% of women reported oral PPS use at baseline. There were statistically significant associations between the number and types of treatments and clinical center, a prior diagnosis of IC, and symptom severity. CONCLUSIONS: The diversity of IC therapies underscores the lack of understanding about the treatment of this syndrome. Further research in IC is essential to develop and to evaluate rational therapies and treatment algorithms. These algorithms should be "evidence based" and should be revised as the underlying etiology and pathophysiology of IC is delineated.

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.

A prospective study of interstitial cystitis: results of longitudinal followup of the interstitial cystitis data base cohort. The Interstitial Cystitis Data Base Study Group.

PURPOSE: We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study, a prospective cohort study of patients with interstitial cystitis. MATERIALS AND METHODS: A total of 637 eligible patients were entered into the study and followed for symptoms of pain, urgency and urinary frequency. Median followup was 31 months. RESULTS: More than 90% of patients were white women with a median age of 43 years. Using the overall pain-urgency-frequency score 7% of participants presented with mild, 44% with moderate and 49% with severe symptoms. Severe urgency in 41% of cases and severe 24-hour frequency in 41% were more common than severe pain in 29%. Of the patients 51% reported nighttime frequency of 2 or more voids. Median duration of interstitial cystitis symptoms was 8 years and 68% of participants were previously diagnosed with the condition. The 36% of patients who withdrew from study or were lost to followup were more likely to have had more severe symptoms at baseline. Patterns of change with time suggest initial symptom improvement due to regression to the mean, and an intervention effect associated with the increased followup and care of cohort participants. Although all symptoms fluctuated, there was no evidence of significant long-term change in overall disease severity. CONCLUSIONS: Our observations support the clinical observation that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time. These results provide a foundation for the design and performance of future clinical trials in interstitial cystitis using these end points in a similar patient population.

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.

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.

Duodenal bicarbonate secretion: eradication of Helicobacter pylori and duodenal structure and function in humans.

BACKGROUND & AIMS: Eradication of Helicobacter pylori expedites duodenal ulcer healing and prevents recurrences. Most patients with duodenal ulcers have impaired proximal duodenal mucosal bicarbonate secretion (DMBS). In patients with inactive, healed duodenal ulcers and normal subjects, the effect of H. pylori infection on DMBS and proximal duodenal secretory function and structure were examined. METHODS: DMBS was quantitated before and after eradication of H. pylori. Mucosal structure (duodenal bulb histopathology) and function (DMBS at rest and stimulated, effect of active vs. healed ulcer and of age) were determined in patients with duodenal ulcers and normal subjects. RESULTS: In patients with duodenal ulcers, H. pylori eradication normalized proximal DMBS. Histological examination of duodenal biopsy samples was comparable in patients with duodenal ulcers and normal subjects without apparent relationship between inflammation and DMBS. Significantly impaired DMBS occurred in response to all agonists tested (luminal acid, prostaglandin E2, and cephalic-vagal stimulation) in patients with duodenal ulcers, suggesting a generalized secretory defect. Neither the presence of active (vs.inactive) ulcer nor age significantly affected bicarbonate secretion. CONCLUSIONS: In patients with duodenal ulcers, eradication of H. pylori normalized proximal DMBS and may thereby reduce ulcer recurrences. Altered DMBS in patients with duodenal ulcers was unrelated to histopathologic abnormalities. Impaired bicarbonate secretion in patients with duodenal ulcers could be caused by a cellular and/or physiological regulatory transport defect possibly related to H. pylori.

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.

Effect of early antibiotic treatment on the formation of sperm antibodies in experimentally induced epididymitis.

This investigation was conducted to evaluate whether or not experimentally produced epididymitis could induce the development of cytotoxic sperm antibodies and if effective antibiotic therapy could reverse the development of immunity to sperm. Escherichia coli was injected into the tail of the epididymis in adult Lewis rats to induce epididymitis and was allowed to incubate for 24 h, 72 h, 8 days, or 15 days. Serum titers of cytotoxic sperm antibodies at these time intervals were determined. Sperm antibody titers began to rise 3 days after inoculation, peaked, and plateaued at 8 days. The titers were negligible in the control rats. Two other groups of rats were inoculated with E. coli in a similar manner and were treated with tetracycline 25 mg/kg/day starting at either 24 h or 8 days after inoculation, for 7 days. The antibody titers became negligible in these two treated groups, the results being statistically significant when contrasted with the infected but untreated groups (p < .001 and < .05, respectively, for the 24-h and 8-day groups). However, histological examination of the antibiotic-treated and untreated specimens revealed significant inflammation and infection of the epididymis in both treated groups. Testicular alterations were consistent in both groups. It is concluded that epididymitis consequent to infection with E. coli can induce cytotoxic antibody formation in Lewis rats. Treatment with appropriate antibiotics may suppress the antibody response either through a direct immunosuppressive effect of the antibiotic or through a decrease in the antigenic load of killed sperm secondary to eradication of the infection.

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.