Philip M. Hanno

Analysis of long-term Elmiron therapy for interstitial cystitis

OBJECTIVESnThe 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 physicians usage study.nnnMETHODSnPatients 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.nnnRESULTSnElmiron 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.nnnCONCLUSIONSnElmiron 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.

Bladder permeability in interstitial cystitis is similar to that of normal volunteers: direct measurement by transvesical absorption of 99mtechnetium-diethylenetriaminepentaacetic acid.

Bladder permeability was directly measured with the radionuclide used clinically for detecting vesicoureteral reflux (99mtechnetium-diethylenetriaminepentaacetic acid, 99mTc-DTPA) in 10 interstitial cystitis patients diagnosed according to National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criterion and compared to 9 sex matched, symptom-free, normal volunteers. After functional bladder capacity was determined (capacity at which the patient demands fluid inflow to stop), the bladder was emptied and 5 mCi. 99mTc-DTPA in 10 ml. of saline were infused followed by normal saline to 80% of functional capacity. This was done to normalize the patients to the same low bladder pressure, since previous studies of rabbits indicated that bladder permeability is low and not significantly different at 20% and 60% of anesthetized bladder capacity (defined as the volume producing an intravesical pressure of 20 cm. water). Radioactivity of 1 ml. serum specimens taken at 0, 2, 15 and 30 minutes after radionuclide infusion was determined in a gamma counter, corrected for radioactive decay and converted to per cent of instilled dose per whole body based on blood volume estimated from body weight for each individual. There was considerable interindividual variability in the absorption between the patients and the volunteers. Analysis of variance of these data showed no statistically significant difference between the patients and controls at any time sampled. These results indicate that while some interstitial cystitis patients have a more permeable bladder than others, the same is true for normal, symptom-free volunteers. Thus, the concept of increased bladder permeability in interstitial cystitis is not supported by this direct measurement of bladder permeability.

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

PURPOSEnWe 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.nnnMATERIALS AND METHODSnBladder 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.nnnRESULTSnIn 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.nnnCONCLUSIONSnBladder 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.

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

OBJECTIVESnTo outline a systematic approach to the evaluation, diagnosis and treatment of interstitial cystitis (IC).nnnMETHODSnA review of the literature as well as of our experience.nnnRESULTSnThe 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.nnnCONCLUSIONnAs 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.

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.

Clozapine-Induced Priapism

Priapism may be a side effect of certain medications. We present a case of priapism associated with the nonphenothiazine antipsychotic drug clozapine. The possible mechanism for the drug-induced priapism is discussed.

Bulbocavernosus reflex studies and autonomic testing in the diagnosis of erectile dysfunction

The electrophysiologic evaluation of patients with erectile dysfunction presents an important diagnostic challenge. The bulbocavernosus reflex (BCR) latency has been commonly used to evaluate these disorders. However, it is a measure of somatic penile innervation, whereas erection is primarily dependent on autonomic function. We evaluated 195 men with erectile dysfunction over a 3 year period. Each had electrophysiologic studies, nerve conduction studies and a BCR. BCR studies were abnormal in only 7%, of which most had diabetes or pelvic trauma. The BCR was the sole electrophysiologic abnormality in only 2%. Autonomic testing (AT) was additionally performed in 19 diabetic and 23 non-diabetic patients. This included sympathetic skin responses and measurement of the Valsalva ratio and heart rate variability with 6/min breathing. In the diabetic group, AT was positive in 63%, and most often was the sole abnormality. The bulbocavernosus reflex is relatively insensitive in the diagnosis of erectile dysfunction. Brief autonomic testing may provide valuable additional data, particularly in diabetics.

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 Hunners 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.

Factitious renal colic

OBJECTIVESnWe 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.nnnMETHODSnWe 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.nnnRESULTSnWe identified 12 patients who presented with renal colic and had a final diagnosis of Munchausens 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

Lack of effect following repeated in vivo exposure of the rabbit urinary bladder to urine from interstitial cystitis patients at low infusion volumes

52,452, with a mean cost per visit of