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.

Urinary urgency - translating the evidence base into daily clinical practice.

AIM: To consider the currently available knowledge and understanding of the symptom of urgency. MATERIALS & METHODS: Each faculty member reviewed the literature base of a different aspect of urgency and along with their personal clinical experience provided a base of evidence for discussion. RESULTS: This overview summarises relevant published literature and the current clinical experience of the authors. DISCUSSION: Whilst the mechanisms producing the sensation of urgency are still not fully understood and we are working within a definition that may complicate measurement and treatment, our pressing need is to effectively manage our patients for whom the practical nature of urgency can be all too apparent. CONCLUSION: Health care professionals have an important role to play today in helping to alleviate the widespread problem of urgency and its consequences.

Pharmacologic erection with intracavernosal injection for men with sexual dysfunction following irradiation: a preliminary report.

Impotence is a possible consequence of treatment of pituitary adenomas and prostatic carcinomas. Following pituitary irradiation, the effect has been attributed to decreased gonadotrophins, while a variety of mechanisms, primarily vascular and neurogenic, have been proposed to explain the impotence following irradiation of prostatic carcinomas. Men with impotence of any etiology have been entered on a program to evaluate prospectively the efficacy of intracavernosal injection of vasoactive compounds in producing a satisfactory erection with pharmacologic means. Ten of these men had developed impotence following therapy for pituitary adenomas (2) or prostatic carcinomas (8). Test doses of 0.1 to 0.5 ml of a phentolamine (1 mg/ml) and papaverine (30 mg/ml) mixture were used; the dose was titrated to produce an erection deemed sufficient for vaginal penetration. All patients achieved a satisfactory response (i.e., tumescence and rigidity) lasting 10 minutes to 3 hours. Seven patients have continued in the pharmacologic erection program, with six patients functioning normally, and the remaining patient noting decreased tumescence after 18 months of treatment, but adequate erections are maintained with supplemental penile ring. Two patients have discontinued intracavernosal injections due to inconvenience, and one patient was lost to follow-up. Recent substitution of prostaglandin E1 (PGE1) has produced similar results and has replaced the phentolamine-papaverine combination. These preliminary results indicate that pharmacologic erection can be achieved in patients with impotence related to the treatment of pituitary and prostatic neoplasms and represents a reasonable alternative to implanted penile prostheses.

Analysis of long-term Elmiron therapy for interstitial cystitis.

OBJECTIVES: The long-term efficacy and safety of Elmiron (oral pentosan polysulfate sodium) in relieving recurring symptoms of interstitial cystitis (IC) were investigated in a long-term, open-label physician's usage study. METHODS: Patients with diagnosed interstitial cystitis who met the study entry criteria received shipments of Elmiron for 3 months at a dose of 100 mg 3 times a day and for the consecutive 3-month periods, provided they completed and returned questionnaires about their disease symptoms, reported any adverse events, and had laboratory data collected before each new shipment. Patients were required to purchase the medication. Responses to questionnaires provided the data reported here. Several symptomatic parameters of the disease (overall improvement, overall improvement in pain and urgency, urinary frequency, and nocturia) were recorded in this way and used to evaluate efficacy. RESULTS: Elmiron usage was correlated with improvements in some symptoms, and these improvements increased with duration of treatment. Some symptoms were improved within 5 months, although most continued to show improvements in both severity rating and in percentage of positive responders over 1 to 2 years. Populations of patients receiving extended treatment, some for > 90 months, showed no further improvement or worsening in symptom values. Forty-six percent of patients dropped out of the study within the first 3 months of Elmiron treatment. The frequency of adverse events was < 4%. The most notable adverse events were reversible alopecia, diarrhea, nausea, headache, and rash. CONCLUSIONS: Elmiron appears to be an efficacious long-term treatment for reducing a constellation of debilitating symptoms associated with interstitial cystitis in some patients. Patients with a positive response to Elmiron appear to maintain this response over time.

Factitious renal colic.

OBJECTIVES: We reviewed our experience with patients with factitious disorders who presented with renal colic to identify their common characteristics and to quantify the cost burden placed on the health care system as a result. METHODS: We retrospectively reviewed the medical records of two Philadelphia area hospitals from 1989 to 1995 to find patients with factitious disorders who presented with renal colic. A control group of patients with nephroureterolithiasis was also identified. RESULTS: We identified 12 patients who presented with renal colic and had a final diagnosis of Munchausen's syndrome or malingering. The incidence of factitious renal colic was 0.6%. Eighty-three percent of these 12 patients were men, had an average age of 32 years, and made a total of 18 hospital visits. Ninety-two percent claimed an intravenous contrast allergy, 25% claimed an allergy to a specific narcotic, and 39% of the hospital visits ended with the patient voluntarily discharged against medical advice. Thirty-three percent were treated elsewhere for similar complaints. Only the number of intravenous contrast allergies and the number of patients leaving against medical advice were statistically different from the control group. The total cost for all factitious visits was $52,452, with a mean cost per visit of $2914. The average bill of those patients who received retrograde pyelograms was $3046 greater than for those who did not. CONCLUSIONS: Factitious disorders should be considered when evaluating patients with an intravenous contrast allergy and renal colic. These patients are likely to leave against medical advice and place a significant cost burden on hospitals.

Adult acute idiopathic scrotal edema.

We report here a rare case of adult acute idiopathic scrotal edema (AISE). Its characteristics and management are the same for adults as for prepubertal boys. AISE typically affects prepubertal boys, with an acute onset of a relatively painless scrotal erythema and subcutaneous edema, which resolves spontaneously, without sequela, in 1 to 3 days. The erythema and swelling can also extend to the perineum, abdomen, or penis. Its diagnosis is primarily made by exclusion. Vital signs, urinalysis, urine and tissue culture, and white blood cell count are normal. Palpably normal scrotal contents on physical examination and thickened scrotal wall and normal testis arterial flow on scrotal ultrasound with color flow Doppler further confirm the diagnosis. Differentiating AISE from a scrotal surgical emergency is essential in order to avoid unnecessary exploration.

Escherichia coli adherence to anion exchange resin. In vitro model for initial screening of potential antiadherence agents.

The first step in developing a bladder infection is attachment of bacteria to the bladder epithelium. Removing the bladder mucin increases bacterial adherence up to a thousand-fold, and this increase can be prevented by pretreating the mucin-deficient bladder with heparin. To develop a rapid, in vitro antiadherence screening assay, we studied the adherence of Escherichia coli to various chromatography resins and the ability of heparin and other agents to antagonize this attachment. The results can be summarized as follows: Although E. coli attached to all resins, only the adherence to the anion exchange resin was inhibited by heparin (up to 95%). Agents which did not effect E. coli adherence to the resin did not affect attachment to the bladder. Agents which inhibited E. coli adherence to the bladder also inhibited E. coli adherence to the resin. Similar to the effect of heparin on E. coli attachment, the adherence of Klebsiella ozaene, Proteus mirabilis, and Streptococcus fecalis to both bladder epithelium and anion exchange resin were also antagonized. These studies indicate that the adherence of E. coli (as well as other bacterial species) to anion exchange resin responds to heparin and other chemical agents in a similar manner as does adherence to the mucin-deficient rabbit urinary bladder. Because of the ease and rapid nature of this in vitro assay, it serves as a useful screen for potential bacterial antiadherence agents and could be used to help elucidate mechanisms of bacterial attachment.

Interstitial cystitis: unexplained associations with other chronic disease and pain syndromes.

OBJECTIVE: To determine the prevalence of concomitant disease in individuals with interstitial cystitis and to compare these results to the general population. METHODS: We used a questionnaire-based study evaluating 12 disease processes and a survey of interstitial cystitis characteristics. The population was 2,405 individuals with interstitial cystitis who responded to the initial survey and an additional 277 individuals who were randomly selected and individually contacted. RESULTS: Allergies, irritable bowel syndrome, and sensitive skin were the most common diseases in the interstitial cystitis population. In comparison to the general population, individuals with interstitial cystitis are 100 times more likely to have inflammatory bowel disease and 30 times more likely to have systemic lupus erythematosus. In addition, allergies, irritable bowel syndrome, sensitive skin, and fibromyalgia have an increased association with interstitial cystitis. CONCLUSIONS: Interstitial cystitis has, as yet, an unexplained association with certain other chronic disease and pain syndromes.

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.

Heparin as antibacterial agent in rabbit bladder.

Previous studies performed in our laboratory indicated that the primary antibacterial defense mechanism of the rabbit bladder is the antiadsorptive action of the surface mucopolysaccharide. The increased bacterial adsorption that occurs when the bladder is denuded of this layer was prevented by the instillation of heparin. Additional studies showed that the protective effect of heparin is inhibited by protamine, a further indication that the bladder's "antiadherence factor" is a mucopolysaccharide. Small amounts of heparin, applied directly to the mucoprotein-deficient bladder or to the surface of the inoculated bacteria, produced a statistically significant reduction in bacterial adsorption.

Nitrofurantoin not surface active agent in rabbit urinary bladder.

It has been recently suggested that nitrofurantoin may induce symptoms of interstitial cystitis by acting as a surface active agent that destroys glycosaminoglycan (GAG) on the bladder surface. Evidence accumulated over the past decade has demonstrated that the bladder surface GAG prevents bacterial adherence. In this experiment, exposure of the bladder lumen to nitrofurantoin at more than twice the therapeutic concentration did not destroy the bladder GAG layer (as evidenced by periodic acid-Schiff histochemistry) nor increase bacterial adherence as did a true surface active agent (Triton X-100). Acid treatment as well as all tested organic solvents except 50% dimethyl sulfoxide (DMSO) also removed the bladder GAG layer and increased bacterial adherence. These results indicate that neither nitrofurantoin nor 50% DMSO has adverse effects on the bladder surface and thus is unlikely to initiate the interstitial cystitis symptom complex by means of surfactant activity.

Effect of repeated instillation of interstitial cystitis urine on the rabbit urinary bladder.

One theory for the etiology of interstitial cystitis (IC) proposes toxic substances in the urine. This hypothesis was tested in our laboratory by infusing urine into the bladders of rabbits twice weekly for six weeks. For the first study rabbits were treated by one-hour biweekly intravesical exposure to urine from a symptomatic interstitial cystitis patient, a normal volunteer, or physiologic saline. For the second study, animals were exposed to both a high and a low molecular weight fraction of urine pooled from 7 interstitial cystitis patients, 7 normal female volunteers, and physiologic saline. At the end of six weeks the animals were cystoscoped and the bladder was removed the following day for histologic and contractile studies. Post-distention glomerulations were observed in 3 of the 4 whole IC urine-treated animals and an ulcer identical to the classic "Hunner's ulcer" was seen in one of these animals. Post-distention petechial hemorrhages were also noted in all 5 of the high molecular weight IC urine-treated animals but in none of the others, suggesting a difference between IC and normal urine. These IC urine-treated groups also showed the greatest degree of histologic changes including edema and plasma cell infiltrates in the lamina propria, submucosa and perivascular tissue. However, there was no statistically significant difference in bladder capacity, micturition patterns, or contractile response of bladder strips. These results indicate that there are substances with nominal molecular weight greater than 10 kD in interstitial cystitis urine that induce changes in the rabbit bladder that resemble bladders of interstitial cystitis patients.

Heparin--examination of its antibacterial adsorption properties.

One of the primary antibacterial defense mechanisms of the bladder is the action of the luminal mucopolysaccharide layer against adsorption of inoculated bacteria. Previous studies have shown that local instillation of the mucopolysaccharide heparin can prevent bacterial adsorption on the bladder mucosa denuded of this "antiadherence factor." To determine whether this action was due to the mucopolysaccharide composition of heparin, or rather to its anticoagulant property, protamine sulfate (a basic protein with anticoagulant properties) was tested for antiadsorptive efficacy. Protamine offered no protection against bacterial adherence in the rabbit model. It appears that heparin's protective effect is unrelated to its action as an anticoagulant.

Preservation of periprostatic autonomic nerves during total perineal prostatectomy by intrafascial dissection.

A modification of Young's total perineal prostatectomy technique is described to prevent damage to the apical branches of the cavernous nerves. Based on anatomic relationships between investing prostatic fascial layers and the neurovascular bundle, emphasis is placed on division of the apical prostatic urethra between the anterolateral endopelvic fascia and Denonvilliers fascia (intrafascial dissection) in avoidance of the apical nerves. Vertical incision in the fused distal portion of Denonvilliers fascia is necessary to make this dissection atraumatic regarding the adjacent paraprostatic neurovascular bundle. Clinical application of this completely intrafascial prostatic dissection is exemplified. It is concluded that careful modification of Young's technique of total perineal prostatectomy may result in increased postoperative potency rates.

Effect of oxybutynin chloride on bladder spasm following transurethral surgery.

A double-blind study of the short-term effects of oxybutynin chloride versus placebo on bladder spasm after transurethral surgery was done in 106 male patients. No significant difference between the placebo and 10 mg. or 20 mg. of the drug was noted.

Management of simple ureterolithotomy closure.

Two methods of ureterotomy closure, loose adventitial closure and an unsutured incision, were evaluated and compared in 89 cases of simple ureterolithotomy. The loose adventitial closure was associated with a significantly shorter period of postoperative urinary drainage and a lower incidence of ureteral narrowing found at follow-up urographic examination.

Invasive carcinoma of prostate presenting as rectal carcinoma.

Prostate carcinoma occasionally can present with rectal obstructive symptoms and an annular constricting lesion of the rectum. Discriminating between primary rectal carcinoma and prostate carcinoma locally invasive to the rectum is of obvious importance because of the different treatments and prognoses. History and physical examination play only a marginal role in differentiating between these two lesions. The diagnosis of prostatic malignancy in patients in this circumstance can be supported by an elevated serum acid phosphatase as well as a bone scan that demonstrates a pelvic/vertebral distribution of bony metastases. The rectal mucosa is usually spared, and a barium enema often will demonstrate tapered margins as opposed to a tumor edge in primary rectal malignancy. Excretory urography often demonstrates hydronephrosis. Rectal biopsy with immunohistochemical staining for prostate specific antigen can direct the origin of a poorly differentiated adenocarcinoma to the prostate. Treatment involves hormonal manipulation with estrogen therapy or orchiectomy. Radiation therapy to the obstructed rectum has provided satisfactory palliation when hormonal manipulation fails.

Testicular plasmacytoma.

The case of a sixty-five-year-old man with multiple myeloma and a testicular plasmacytoma is described. This represents the thirty fourth reported case of testicular plasmacytoma and the first in which immunoperoxidase histochemistry has been used to demonstrate that the testicular plasma cells contain immunoglobulin of the same isotype as the patient's paraprotein. The clinical and morphologic features of previously reported testicular plasmacytoma are reviewed.