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PubMed2004

Treatment of interstitial cystitis.

Although the symptoms of interstitial cystitis (IC)--a debilitating, chronic disease characterized by urinary urgency and frequency, and bladder and pelvic pain on bladder filling--are easily confused with those of urinary tract infections, there is an absence of an underlying infection, and antibiotic therapy is of no therapeutic benefit. Severe cases of this disorder, which affects mainly women, can have a great negative impact on the quality of life of patients because of extreme urinary frequency. The diagnosis of IC is difficult and should be based on patient history, physical examination, and cystoscopy. A large number of pharmacologic treatments have been used to treat this condition with limited success, including pentosan polysulfate, heparin, antihistamines, tricyclic antidepressants, intravesical dimethyl sulfoxide, and bacille Calmette-Guérin. Among the potentially effective new treatment modalities currently under investigation are suplatast tosilate, resiniferatoxin, botulinum toxin, and gene therapy to modulate the pain response. As knowledge of the pathogenesis of IC increases through intensified research, the ability to provide effective treatment to patients with this disease will improve.

Cystitis, Interstitial↗

PubMed1997

Concentrations of specific epithelial growth factors in the urine of interstitial cystitis patients and controls.

PURPOSE: Interstitial cystitis (IC) is a chronic bladder disease for which the etiology is unknown. Because the bladder epithelium is often abnormal in IC, we determined whether the levels of specific urine growth factors postulated to be important for bladder epithelial proliferation are altered in IC. MATERIALS AND METHODS: ELISAs were used to determine levels of epidermal growth factor (EGF), insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), and heparin binding epidermal growth factor-like growth factor (HB-EGF) in urine specimens from women with IC, asymptomatic women without bladder disease, and women with bacterial cystitis. RESULTS: Urine HB-EGF levels were specifically and significantly decreased in IC patients as compared to asymptomatic controls or patients with bacterial cystitis, whether expressed as concentration (amount per volume of urine) or the amount relative to urine creatinine in each specimen. In contrast, urine EGF, IGF1, and IGFBP3 levels were all significantly elevated in IC patients compared to asymptomatic controls. Further, the amounts of urine EGF and IGF1 were also elevated in IC patients as compared to patients with bacterial cystitis, and urine IGFBP3 levels were significantly elevated when expressed per milligram of urine creatinine. CONCLUSIONS: These findings indicate that complex changes in the levels of urine epithelial cell growth factors (EGF, IGF1, and HB-EGF) and a growth factor binding protein (IGFBP3) are associated with IC. While EGF, IGF1, and IGFBP3 levels are either the same or increased in the urine of IC patients as compared to patients with bacterial cystitis or asymptomatic controls, HB-EGF levels are significantly decreased in the urine of IC patients. Understanding the reasons for these changes may lead to understanding the pathogenesis of this disorder.

Adult↗

PubMed1999

Care of the patient with interstitial cystitis: current theories and management.

Interstitial cystitis is a disease process that has only come into focus over recent years. Researchers are looking for a cause of this painful and frustrating disorder of the bladder, but currently, only theories exist. Nurses must understand the pathophysiology of the disease and the dysfunction of the bladder to educate and assist the patient in the management of this chronic process. This report provides the nurse with information and education on the symptoms, pathophysiology, nursing diagnoses, and potential treatment modalities.

Adult↗

PubMed2002

Interstitial cystitis.

Appropriate diagnostic tests for interstitial cystitis remain uncertain. One or more promising markers for this disease have been described which may provide a noninvasive means for diagnosis as well as clues to pathogenesis of this disease. Treatment remains empiric.

Bacterial Infections↗

PubMed2005

Bladder Adelta afferent nerve activity in normal cats and cats with feline interstitial cystitis.

PURPOSE: Symptoms associated with interstitial cystitis (IC) (urinary frequency, urgency and pain) resemble those in cats diagnosed with feline IC (FIC). Patients with IC also show enhanced sensitivity to intravesical application of KCl solution. In the current study we compared the effect of bladder distention and intravesical infusion of KCl solution on Adelta bladder afferent nerve activity in normal and FIC cats. MATERIALS AND METHODS: Cats were anesthetized with alpha-chloralose (60 to 70 mg/kg intravenously). Single and multiunit afferent nerve activity was recorded with platinum electrodes from fibers dissected from the transected pelvic nerve. Bladder Adelta afferents were activated by bladder distention at constant pressures (5 to 80 cm H2O) by infusing saline or KCl solution (80 to 300 mM). RESULTS: Increasing bladder pressure by saline infusion over a range of constant pressures (5 to 80 cm H2O) increased afferent firing in normal and FIC cats. However, the slope of the pressure-firing curve was significantly steeper in cats with FIC. In normal cats KCl infusion (80 to 300 mM) into the bladder produced a pressure-firing curve similar to that induced by saline infusion. However, in FIC cats KCl at concentrations of 150 to 300 mM produced almost complete inhibition of afferent firing at pressures between 30 and 80 cm H2O. CONCLUSIONS: These data suggest that 1) bladder Adelta afferents in FIC cats are more sensitive to pressure changes than are afferents in normal cats and 2) the inhibition of afferent firing by high concentrations of KCl in FIC cats is likely the result of afferent nerve depolarization and it is consistent with the idea of increased permeability of bladder epithelium in FIC.

Afferent Pathways↗

PubMed2002

Interstitial cystitis: diagnosis and treatment options.

Interstitial cystitis (IC) is a disease complex characterized by urinary frequency, urgency, and bladder pain without an identifiable cause. Essentially, IC is a diagnosis of exclusion. The lack of knowledge of pathophysiology remains the biggest hurdle in diagnosis and treatment of this puzzling and troublesome disorder. Nevertheless, several recent advances, coupled with increased public awareness of this disease, make it easier for physicians and patients to effectively deal with IC.

Administration, Intravesical↗

PubMed2005

[Interstitial cystitis--its diagnostics and treatment].

Interstitial cystitis is a chronic, non-bacterial inflammatory disorder of the wall of the urinary bladder and it manifests with very painful symptoms. Initially it can resemble a bacterial inflammation of the urinary bladder. This syndrome is characterised with motor and sensory dysfunction of the urinary bladder. The difficulties can be classified into so-called syndrome of the chronic pelvic pain. Increasing incidence, chronicity of this disorder and specific treatment leads to the reinterpretation of the chronic inflammation of the urinary tract diagnosed in the past and to the modification of the treatment of these patients. Because of the polymorphic difficulties and the psychosomatic manifestations, IC can lead to invalidity of the patient.

Adolescent↗

PubMed2007

Bladder necrosis following hydrodistention in patients with interstitial cystitis.

PURPOSE: Bladder hydrodistention is used to diagnose and treat patients with interstitial cystitis. This procedure has been shown to have minimal morbidity and provide symptomatic relief in a subset of patients with interstitial cystitis. We report our experience with almost total bladder necrosis after hydrodistention at 2 institutions. To our knowledge this rare complication has not been previously reported in the literature. We also reviewed the literature regarding complications of hydrodistention and discuss their possible etiology. MATERIALS AND METHODS: We report 3 cases of bladder necrosis after therapeutic hydrodistention for interstitial cystitis at 2 institutions. All records were reviewed, and the clinical presentation, findings and treatments are discussed. A literature review was performed to evaluate the effectiveness and complications of hydrodistention for interstitial cystitis. RESULTS: There were 2 female and 1 male patient between ages 29 and 46. All patients had a previous diagnosis of interstitial cystitis and had been previously treated with hydrodistention. All patients presented with severe abdominal pain and had necrosis of the entire bladder wall with sparing of the trigone. Two patients were treated with supratrigonal cystectomy. A review of the literature revealed little data on the effectiveness of hydrodistention for interstitial cystitis. CONCLUSIONS: Vesical necrosis is a rare but devastating complication of hydrodistention. It can occur in young patients in the absence of a contracted bladder and it usually presents as severe postoperative abdominal pain. At exploration bladder necrosis with sparing of the trigone was observed. All patients required enterocystoplasty.

Adult↗

PubMed2006

Uronate peaks and urinary hyaluronic acid levels correlate with interstitial cystitis severity.

PURPOSE: Levels of uronate, a basic component of urothelial glycosaminoglycans, are increased in urine specimens of patients with interstitial cystitis with severe symptoms. In this study we examined the urinary glycosaminoglycan profile and correlated the profile and urinary hyaluronic acid (a glycosaminoglycan) levels with symptom severity. MATERIALS AND METHODS: Urine specimens and completed O'Leary-Sant interstitial cystitis symptom and problem indexes questionnaires were obtained from 29 patients with interstitial cystitis, 14 normal individuals, and 14 patients with other benign pelvic and bladder conditions. Patients with interstitial cystitis were divided into group 1-1 or both indexes less than 50% maximum score, and group 2-both indexes 50% of maximum score or greater. All patients met the National Institutes of Diabetes and Digestive and Kidney Diseases criteria except regarding glomerulation. In a followup study 30 urine specimens were collected from 8 patients with interstitial cystitis and from 4 normal individuals during 12 months. The urinary glycosaminoglycan profile was determined by gel filtration chromatography. Glycosaminoglycan peaks were analyzed by polyacrylamide gel electrophoresis. Urinary hyaluronic acid levels were determined by the hyaluronic acid test. RESULTS: Group 2 urine specimens contained 3 uronate peaks, whereas urine specimens from normal individuals and patients in group 1 contained 1 or 2 peaks. Peak 1 consisted of macromolecular glycosaminoglycans whereas peaks 2 and 3 contained oligosaccharides. Urinary hyaluronic acid levels were 3 to 4-fold increased in group 2. Glycosaminoglycan profile and hyaluronic acid levels detected interstitial cystitis severity with 83% sensitivity, and 89.7% and 74.4% specificity, respectively. Interstitial cystitis urothelial cells/tissues also over expressed hyaluronic acid synthase 1 (which synthesizes hyaluronic acid) compared to normal urothelial cells/tissues. In the followup study urinary uronate levels, glycosaminoglycan profile and hyaluronic acid levels detected patients with severe symptoms with 73% sensitivity and 87% to 94% specificity. In both studies uronate, glycosaminoglycan profile and hyaluronic acid levels significantly correlated with interstitial cystitis severity (p <0.001). CONCLUSIONS: Urinary glycosaminoglycan profile, uronate content and hyaluronic acid levels are potentially useful markers for monitoring interstitial cystitis severity, and are likely to be involved in interstitial cystitis pathophysiology.

Adult↗

PubMed1999

[Interstitial cystitis: surgical treatment].

Surgical therapy of interstitial cystitis must never be considered a first option but must be reserved for cases, less than 10%, in which conservative therapy has proven ineffectual. Surgical therapy includes a variety that started at the turn of the century. Neurosurgical denervation and perivesical denervation like cysto-cystoplasty and cystolysis, manipulate the innervation to reduce the bladder's hypersensitivity. This surgical approach may be considered in patients in whom bladder capacity is normal. The results are uncertain and the complications like neurogenic bladder relevant. Enterocystoplasty is much more widespread because interstitial cystitis is a benign disease that rarely required radical surgery. Augmentation cystoplasty and substitution cystoplasty are two variants but only the later has a rationale as it involves the resection of the detrusor which is the source of the pain. Detubularization drastically reduced urinary incontinence. The resection of the detrusor can be supratrigonal, subtrigonal or at the proximal urethra like in the orthotopic neobladder. If urinary diversion is chosen, the bladder must be removed. Before recommending surgical therapy each patient should undergo tests for the localization of the pain; moreover psychological and gynaecological evaluations should be made. If the bladder capacity exceeds 400 cc surgical operation is not advisable. If, on the other hand, the bladder capacity is lower than 400 cc substitution cystoplasty is first choice. If the patient suffers from trigonal cystitis or urethral hypersensitivity, urinary diversion is a better therapy. According to the questionnaires send to the Urologic Departments in Lombardy in 1998, the most widespread type of operation seems to be supratrigonal cystectomy + enterocystoplasty and augmentation cystoplasty. Subtrigonal cystectomy or urinary diversion are only occasionally chosen; continent pouch is the least frequent therapy at all.

Adult↗

PubMed1994

Interstitial cystitis. A patient's perspective.

Interstitial cystitis is a debilitating bladder disorder that affects up to 450,000 people in the United States, 90% of whom are women. Confusion in defining and understanding interstitial cystitis has resulted in the failure to diagnose and treat thousands of afflicted patients, committing them to a life of intractable pain. Even with diagnosis, there are no uniformly effective treatments. It is extremely important that these patients have the understanding and support of the medical community, and they should develop a constructive and effective relationship with their physician and other urologic caregivers.

Cystitis↗

PubMed2001

Increased urinary leukotriene E4 and eosinophil protein X excretion in patients with interstitial cystitis.

PURPOSE: The role of cysteinyl containing leukotriene C4, D4 and E4, and eosinophil protein X in interstitial cystitis is unknown. Leukotriene E4, the end product of cysteinyl containing leukotrienes, and eosinophil protein X are markers of the activation of mast cells and eosinophils, respectively. Cysteinyl containing leukotrienes are potent and specific chemoattractants for eosinophils. We compared the urinary excretion of leukotriene E4 and eosinophil protein X in patients with interstitial cystitis and in healthy controls. MATERIALS AND METHODS: Morning spot urine samples from nine patients with interstitial cystitis who fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria were collected on the day of cystoscopy with biopsies. Aliquots of urine specimens were immediately centrifuged and the supernatants were stored at -80C until use. Urine samples from 9 healthy women served as controls. Urinary leukotriene E4 and eosinophil protein X were measured by enzyme immunoassay and radioimmunoassay, respectively. All determinations were performed in duplicate and normalized to urine creatinine. RESULTS: Leukotriene E4 and eosinophil protein X were significantly increased in the morning urine of patients with interstitial cystitis compared with controls. The mean urinary excretion of leukotriene E4 plus or minus standard deviation was 148.8 +/- 62.5 and 62.2 +/- 17.5 ng./mmol. creatinine in patients and controls (p = 0.003), while the mean urinary excretion of eosinophil protein X was 109.7 +/- 70.4 and 43.7 +/- 22.0 microg./mmol. creatinine, respectively (p = 0.01). All urine cultures were negative. The mean mast cell count in detrusor biopsies in the interstitial cystitis group was 41 cells per mm.2 (range 5 to 84). Eosinophilic granulocytes were occasionally observed in the submucosa but not in the detrusor. CONCLUSIONS: Our study shows that patients with interstitial cystitis and detrusor mastocytosis have increased urinary leukotriene E4 and eosinophil protein X. It is possible that cysteinyl containing leukotrienes and eosinophil protein X are involved in the pathogenesis of interstitial cystitis. Urinary leukotriene E4 and eosinophil protein X may be useful markers for assessing the grade of activation of mast cells and eosinophils in patients with interstitial cystitis and/or for confirming the diagnosis. However, it remains to be investigated whether the increase in urinary leukotriene E4 and eosinophil protein X correlates with interstitial cystitis symptoms.

Adult↗

PubMed1994

Abnormal flow cytometry profiles in patients with interstitial cystitis.

Flow cytometry was performed on bladder cells from patients with interstitial cystitis and control patients. Cells were processed in standard fashion for flow cytometry with propidium iodide staining and analysis was restricted to samples with sufficient cells for cytokeratin gating and acceptable coefficients of variation. Of 14 interstitial cystitis patients 4 (29%) demonstrated aneuploid deoxyribonucleic acid (DNA) profiles as evidenced by a discrete peak with a DNA index of 1.2 or greater in the cytokeratin positive population. The aneuploid peak accounted for up to 54% of the cytokeratin positive population in these samples. No such aneuploid DNA profiles were evident in specimens obtained from control patients. A significant DNA tetraploid population, as evidenced by a 4C (G2) peak greater than 20%, was observed in 6 of 14 interstitial cystitis patients (43%) and 8 of 11 controls (72%). Manual counting of the per cent of binucleated cytokeratin positive cells in the cytokeratin stained population and nuclear preparations of several samples for flow analysis indicate that apparent DNA tetraploidy in the interstitial cystitis and control patients is due to an abundance of binucleated cells. Aneuploid DNA profiles on barbotage specimens from interstitial cystitis patients may reflect a real karyotypic abnormality or altered chromosome complement (true aneuploidy), abnormal chromatin structure or abnormal cytoplasmic binding of the propidium iodide stain. This finding may signal an underlying abnormality of the epithelial cell population in some patients with the clinical diagnosis of interstitial cystitis.

Adult↗

PubMed1993

Evaluation of urothelial Tamm-Horsfall protein and serum antibody as a potential diagnostic marker for interstitial cystitis.

Demonstration of adherence of Tamm-Horsfall protein to bladder epithelium has been suggested as a potential diagnostic test for interstitial cystitis. Bladder specimens from 18 interstitial cystitis patients were evaluated by indirect immunoperoxidase techniques using a Tamm-Horsfall protein specific monoclonal antibody to determine the diagnostic value of the staining results. The study population consisted of 7 severely diseased patients who required cystectomy with urinary diversion and 11 other patients meeting National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criteria for interstitial cystitis. We were unable to detect intraepithelial or surface-bound Tamm-Horsfall protein in any of the biopsy tissues. Human kidney tissue, similarly fixed and processed, consistently demonstrated Tamm-Horsfall protein staining of the kidney tubules. The monoclonal antibody also reacted on Western blots against urinary Tamm-Horsfall protein. Although antibody (alpha-Tamm-Horsfall protein) reactivity was measured by enzyme-linked immunosorbent assay in sera from interstitial cystitis patients, the titers did not differ statistically from those measured in sera from those without interstitial cystitis. Together, these results make it unlikely that immunohistochemical detection of Tamm-Horsfall protein will have diagnostic value in interstitial cystitis. Whether Tamm-Horsfall protein has a role in the pathogenic processes involved in this disease is not yet known. These findings do not eliminate the possibility that some interstitial cystitis patients will have abnormalities associated with the biochemical and physiological functions of Tamm-Horsfall protein.

Adult↗

PubMed2000

Clinical conversations: nurses who work with patients with interstitial cystitis.

Nurses who work with patients with interstitial cystitis agree these patients demand considerable clinician time. Interstitial cystitis is a chronic disease with several etiologic theories explaining the syndrome. Diagnosis and treatment are already updated in the preceding article by Dr. Peters. Conversations with nurses who practice in different areas of the United States extend this discussion by addressing patient issues and offering specific nursing advice.

Combined Modality Therapy↗

PubMed1990

Diagnosis of interstitial cystitis.

We reviewed clinical and histological findings in 55 patients with interstitial cystitis and 21 with voiding dysfunction secondary to other pathological conditions. Of our interstitial cystitis patients 36% would fail to meet the research definition proposed at a recent National Institutes of Health workshop. Detrusor mastocytosis was present in 64% of our interstitial cystitis patients compared to 80% of the noninterstitial cystitis group. There was no statistically significant difference in mean detrusor mast cell counts between interstitial cystitis and noninterstitial cystitis patients. Biopsies of 12 patients who did meet the proposed National Institutes of Health research definition were evaluated by immunohistochemical techniques. Early results are inconclusive. These studies indicate that interstitial cystitis is a complex disease whose diagnosis presently still must be made from a symptom complex rather than from objective histological criteria, including mastocytosis or the presence of any specific immunoreactive cell.

Cell Count↗

PubMed1999

A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis.

PURPOSE: Nitric oxide synthase activity is decreased in the urine of patients with interstitial cystitis compared to the urine of controls. In a preliminary trial oral L-arginine, the substrate for nitric oxide synthase, increased urinary nitric oxide synthase activity and improved interstitial cystitis symptoms. This randomized, double-blind, placebo controlled study further investigates the efficacy of L-arginine treatment for interstitial cystitis. MATERIALS AND METHODS: A total of 53 interstitial cystitis patients were assigned to receive daily 1,500 mg. L-arginine or placebo orally for 3 months. Interstitial cystitis symptoms were assessed by interviews at 2 weeks, and 1, 2 and 3 months. RESULTS: The trial was completed by 21 of 27 patients in the L-arginine group and 25 of 26 in the placebo group. Using per protocol analysis 29% (6 of 21 patients) in the L-arginine group and 8% (2 of 25) in the placebo group were clinically improved by the end of the trial (p = 0.07). A Likert scale showed greater global improvement in the L-arginine group (48%, 10 of 21) compared to the placebo group (24%, 6 of 25) at 3 months (p = 0.05) with a decrease in pain intensity (p = 0.04), and tendency toward improvement in urgency (p = 0.06) and frequency of pain (p = 0.09). Using an intention to treat approach to analysis there were no differences between groups. CONCLUSIONS: Oral L-arginine (1,500 mg. daily) may decrease pain and urgency in a subset of interstitial cystitis patients.

Administration, Oral↗

PubMed1993

The natural history of interstitial cystitis: a survey of 374 patients.

A survey directed at determining the natural history of interstitial cystitis was conducted at our clinic. Information on demographics, risk factors, symptoms, pain and psychosocial factors was elicited from 374 patients who satisfied the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criteria for interstitial cystitis and had all been diagnosed as having interstitial cystitis by a urologist. With regard to demographics, patients were predominantly female (89.8%) and white (94.1%), with a mean age of 53.8 +/- 0.7 years (standard error) and age at the first symptoms of 42.5 +/- 0.8 years. Information on 25 potential risk factors included 44.4% of the women reporting hysterectomy, 38.2% of the patients having strong sensitivities or allergic reactions to medication and only 2.7% being diabetic. With regard to interstitial cystitis symptoms, frequency and urgency were reported by 91.7% and 89.3% of the patients, respectively, while pelvic pain, pelvic pressure and bladder spasms were reported by more than 60% of respondents and burning by 56%. Location and degree of pain were also reported. Urination relieved or lessened interstitial cystitis pain for 73.6% of the patients and medication was effective for 46.8%. Other behaviors (for example hot baths, heating pads, lying down or sitting) were less effective. Conversely, stress, constrictive clothing and intercourse increased interstitial cystitis pain in more than 50% of the patients. In addition, acidic, alcoholic or carbonated beverages, and coffee or tea increased interstitial cystitis pain in more than 50% of the patients. More than 60% of the patients were unable to enjoy usual activities or were excessively fatigued and 53.7% reported depression. Travel, employment, leisure activities and sleeping were adversely affected in more than 80% of the patients. Pain location and degree differed significantly between patients with and without ulcers in the bladder. In addition, there was an apparent plateau in the frequency and urgency among patients after approximately 5 years with symptoms.

Adult↗