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Successful treatment of interstitial cystitis with sodium pentosanpolysulfate.

The surface of the bladder is lined by a layer of sulfonated glycosaminoglycans, of which the nonspecific anti-adherence effect is reproduced by synthetic sulfonated glycosaminoglycans. This mucous layer appears to be the most important line of defense between the transitional cells and all harmful substances in the urine. Many disease states may be associated with a deficiency in the anti-adherence activity of the glycosaminoglycan layer and may benefit from treatment with synthetic glycosaminoglycans. One such disease is interstitial cystitis. We administered oral sodium pentosanpolysulfate (Elmiron), a synthetic analogue of a sulfonated glycosaminoglycan, to 24 patients with interstitial cystitis. Within 4 to 8 weeks of initiation of treatment 20 patients experienced a decrease of at least 80 per cent in pain, urgency and nocturia, and 2 experienced a 50 to 80 per cent decrease in these symptoms. The 22 patients who responded continue to experience progressive improvement with time.

Humans↗

Intravesical treatment of severe bacillus Calmette-Guerin cystitis.

OBJECTIVE: Intravesical instillation of bacillus Calmette-Guerin (BCG) is an established treatment of carcinoma in situ and recurrent superficial bladder tumours. The inflammatory reaction due to BCG provokes cystitis of short duration as a frequent side effect. When the symptomatology is severe and long-lasting, different systemic treatments have been administered with varying degrees of efficacy. MATERIAL AND METHODS: We have studied the treatment of severe BCG cystitis with a anaesthetic anti-inflammatory solution administered by intravesical instillations to 16 patients. RESULTS: Good results were obtained in 94% of the cases, with immediate clinical improvement in terms of pain and urinary symptoms, and with no side effects. CONCLUSIONS: This treatment is inexpensive and easy to administer. We consider that it offers a useful option to solve an infrequent but very annoying problem for the patients.

Adjuvants, Immunologic↗

Interstitial cystitis and pelvic floor dysfunction: a comprehensive review.

Interstitial cystitis is a clinical condition occurring predominantly in women and is characterized by urinary frequency, urgency, and pain. Patient symptoms have the potential to significantly affect quality of life, posing a challenge to some to perform activities of daily living. This article comprehensively reviews the literature on the epidemiology, etiology, evaluation, and treatment of interstitial cystitis, and considers commonly associated pelvic floor dysfunction.

Journal Article↗

Cyclophosphamide cystitis in mice: behavioural characterisation and correlation with bladder inflammation.

The generation of transgenic 'knock-out' mice which lack genes relevant to pain is becoming increasing common. However, only one visceral pain model, the writhing test, is available in mice. The aim of this study was to adapt cyclophosphamide cystitis, a model of inflammatory visceral pain described in rats, for use in mice, and to characterise its behavioural effects. The toxic metabolites of systemically-administered cyclophosphamide are excreted in the urine, and induce bladder inflammation. We compared the effects of cyclophosphamide (100 and 300 mg/kg i.p., 4 h survival period) and vehicle (saline) in male mice on spontaneous behaviour (4 h continuous video-tape, and a 5-min Open Field test after 4 h). Involvement of the urinary bladder and other abdominal tissues was assessed by macroscopic examination and measurement of Evan's Blue plasma extravasation. Cyclophosphamide (300 mg/kg) produced significant changes in behaviour, including 22 +/- 6 min of 'crises' of visceral pain-related behaviour and a 53% reduction in activity, and also induced haemorrhage and substantial plasma extravasation in the bladder, but no change in other abdominal tissues. We conclude that cyclophosphamide cystitis has many advantages as a model of sub-acute, inflammatory visceral pain in mice. It does not require surgery or intubation, and we have found it to produce consistent, reproducible and quantifiable behavioural changes, which are significantly correlated with the degree of bladder inflammation in the absence of inflammation of other abdominal tissues. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

Glycoaminoglycan (GAG) deficiency in protective barrier as an underlying, primary cause of ulcerative colitis, Crohn's disease interstitial cystitis and possibly Reiter's syndrome.

Ulcerative colitis, Crohn's disease and interstitial cystitis share many common features, the most important of which is a defect in the glycoaminoglycan (GAG) defensive barrier. This defect allows penetration of toxins causing localized inflammatory response, followed by fibrosis and distant pathological changes, together with a myriad of biochemical and immunological changes. The latter has caused confusion as to etiology of the aforementioned disorders. This hypothesis is somewhat supported by the fact that agents such as glucosamine and pentosan polysulphate (Elmiron) that replace the GAG layer, improve the conditions. The potential for extrapolation of this hypothesis to atherosclerosis and arthropathies exists. There is a great danger in modern medical research that if one misses the wood for the trees, one becomes hopelessly lost in the minutiae of research. At present, it is embarrassing that ulcerative colitis (UC), Crohn's (CR) and interstitial cystitis (IC) are the cause of a great deal of morbidity and occasionally mortality, yet after intensive research, the etiology and effective treatment eludes us. The research in the past has focused extensively on inflammatory response in the mucosal lining, and biochemical, infective and immunological changes in the serum. This has led to a vast array of research pathways that seem at the present time to be totally lost and, might I say, aimless in direction, as a cause for these conditions, that remain amongst the most imperically treated in modern medicine. Another possible syndrome in this class would be Reiter's, which has many features in common with the above. The basic tenet of a GAG deficiency hypothesis is that, as shown in Figure 1A, an intact GAG layer provides, firstly, a mechanical and electrostatic defence against penetration of infective agents, toxins, antigenic protein moieties, etc. and, secondly, the prevention of extravasation of body fluid components. A degraded GAG layer is the start of the disease cascade of the above group of illnesses.

Arthritis, Reactive↗

A case of interstitial cystitis and Hunner's ulcer in a domestic shorthaired cat.

An 8-year-old spayed, domestic, shorthaired cat was examined with signs of feline urological syndrome which were unresponsive to previous therapy with antibiotics and urinary acidifiers. Biopsy of the bladder revealed signs of cystitis similar to interstitial cystitis in humans. Treatment with sodium pentosan polysulphate resulted in a decreased frequency of urination and resolution of haematuria. This condition may be more widespread in cats than realised, as it is only by bladder biopsy that diagnosis can be made.

Journal Article↗

Treatment options for acute uncomplicated cystitis in adults.

Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of </=10-20%. Otherwise fluoroquinolones are recommended. Alternatives are fosfomycin trometamol or beta-lactams, such as second- or third-generation oral cephalosprins or pivmecillinam, especially when fluoroquinolones are contraindicated or a high proportion (>10%) of Escherichia coli strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis.

Journal Article↗

[Hemorrhagic cystitis related to the high-dose conditioning therapy in a bone marrow recipient].

Hemorrhagic cystitis (HC) is the syndrome of hematuria combined with symptoms of lower urinary tract irritation in the absence of bacterial infection or generalized hemorrhagic diathesis. HC often occurs as a difficult complication after autologous as well as allogeneic hematopoietic cell transplantation (HCT). It may be secondary to pretransplant preparative regimen (chemotherapy and/or radiation therapy) or viral infection by adenovirus, JC and BK viruses. The most effective treatment for HC has not been established yet. We report a case of a 17-year-old male with common acute lymphoblastic leukemia (cALL) in second CR, who was treated with high-dose chemotherapy (BuCy conditioning regimen) followed by autologous bone marrow transplantation (ABMT), complicated by hemorrhagic cystitis on day 0 (several hours after infusion of transplant material). The immediate use of increased dose of 2-mercaptoethane sulfonate sodium (mesna), bladder irrigation and intensive hydration with forced diuresis resulted in resolution of macroscopic hematuria on day +3 after the transplant and urinary tract recovery with normalization of urine analysis parameters on day +7.

Adolescent↗

Interstitial cystitis: characterization and management of an enigmatic urologic syndrome.

The enigmatic urologic condition known as interstitial cystitis has an estimated prevalence of 0.01% to 0.50% of the female population. Its etiology is unknown but may involve microbiologic, immunologic, mucosal, neurogenic, and/or other, as yet undefined, agents. There is no gold standard for the diagnosis of interstitial cystitis; rather, it is a diagnosis of exclusion. It is impossible to provide a purely evidence-based treatment strategy, but review of available evidence suggests that conservative supportive therapy (including diet modification); oral treatment with pentosan polysulfate, amitriptyline, hydroxyzine, or cimetidine; and intravesical treatments with heparinoids, dimethyl sulfoxide, alkalized lidocaine, or bacille Calmette-Guérin may be effective in some patients.

Journal Article↗

Treatment approaches for interstitial cystitis: multimodality therapy.

Interstitial cystitis is an increasingly common disease characterized by urgency, frequency, and pelvic pain. Its etiology is poorly understood but is likely to be multifactorial. A proposed pathophysiology describing a cascade of events, including epithelial dysfunction, mast cell activation, and neurogenic inflammation, is presented. Using this model, multimodality therapy regimens have been developed that treat all components of this cascade. Multimodality therapy appears more effective than single agents in the treatment of interstitial cystitis.

Journal Article↗

Intestitial cystitis.

Interstitial cystitis, a disease of unknown origin which occurs predominantly in women, causes great pain and considerable disability. In most cases, the long interval between onset of symptoms and establishment of the diagnosis is due to a lack of familiarity with the disease.Although there is no "cure," several forms of therapy may lead to improvement. In a series of 27 patients, 15 received benefit from distention of the bladder through the use of a solution of monoxychlorosene.

Anti-Infective Agents, Local↗

Prevalence of clinically confirmed interstitial cystitis in women: a population based study in Finland.

PURPOSE: Interstitial cystitis (IC) is a clinical condition occurring predominantly in women that is characterized by irritative voiding symptoms, including urinary frequency, urgency and pain. To our knowledge its etiology is unknown and little is known about its occurrence. We evaluated the prevalence of IC in women in Finland. MATERIALS AND METHODS: A total of 2,000 participants were randomly selected from the Finnish population register. Urinary symptoms were evaluated using the validated O'Leary-Sant IC symptom and problem index questionnaire. Women with moderate or severe symptom scores (7 or higher) without any urinary tract infection during the last month were invited to undergo clinical examination. RESULTS: Of the 1,331 respondents 32 had moderate or severe symptoms involving a suspicion of IC, of whom 21 underwent clinical evaluation. Three women were found to have probable IC and 4 had possible IC. Thus, the prevalence of clinically confirmed probable IC in women was 230/100.000 (95% CI 100 to 360) and that of possible/probable IC was 530/100.000 (95% CI 140 to 910). Considering the lack of information on 8 patients with urinary symptoms the corrected estimates were 300/100,000 (95% CI 120 to 770) and 680/100,000 women (95% CI 360 to 1,300), respectively. CONCLUSIONS: Our results based on a large and representative population, and clinically confirmed diagnoses indicate that IC is substantially more common than previously thought.

Adolescent↗

Interstitial cystitis and panic disorder: a potential genetic syndrome.

BACKGROUND: Evidence from a genetic linkage study had suggested a possible syndrome in some families with panic disorder (PD). This syndrome includes bladder problems (possibly urinary interstitial cystitis [IC]), thyroid disorders, chronic headaches/migraine, and/or mitral valve prolapse. In 19 multiplex families with PD, one marker (D13S779) on chromosome 13 gave a logarithm of odds score of more than 4 when individuals with any of the syndrome conditions were analyzed as affected. Families with the bladder problems yielded the highest logarithm of odds scores. These findings were replicated in an extended sample of 60 families. Whereas PD had been well characterized by direct interview, the urologic problems had been found only via medical history checklists and records. A case review by a board-certified urologist suggested they could be IC. OBJECTIVE: To determine whether patients diagnosed as having IC by urodynamics and/or cystoscopy and their first-degree relatives (FDRs) have increased rates of the syndrome conditions, thus validating that the bladder problems observed in the linkage study could be IC and providing further support for the panic syndrome. DESIGN: Case-control and family history study. SETTING: Two metropolitan urology clinics. PARTICIPANTS: One hundred forty-six probands (67 with IC and 79 with other urologic disorders) and 815 FDRs. MAIN OUTCOME MEASURES: Lifetime rates of syndrome conditions in probands and FDRs who were blind to urologic or psychiatric diagnoses in the proband. RESULTS: Compared with patients without IC, patients with IC had a significantly higher lifetime prevalence of PD (controlling for age and sex) (odds ratio, 4.05; 95% confidence interval, 1.22-13.40; P =.02) and a higher lifetime prevalence of any of the syndrome disorders (controlling for age and sex) (odds ratio, 2.22; 95% confidence interval, 0.89-5.54; P =.09). First-degree relatives of probands with (vs without) IC were significantly more likely to have PD, thyroid disorder, urologic problems, and any of the syndrome disorders (controlling for age and sex of the relative and sex of the proband) (adjusted odds ratio, 1.95; 95% confidence interval, 1.13-3.38; P =.02). These results in relatives were not influenced by PD in probands, and did not change substantially when controlling for the proband-relative relationship, modeling age as a categorical (vs continuous) variable, or excluding FDRs with PD. There were no interactions between proband IC status and sex of the relative. CONCLUSIONS: The increased frequency of seemingly disparate disorders in patients with IC and their FDRs is consistent with the genetic linkage findings in families with PD. These findings suggest that the bladder problems observed in the linkage study may be IC. The hypothesis that there is a familial, possibly pleiotropic, syndrome that may include IC, PD, thyroid disorders, and other disorders of possible autonomic or neuromuscular control deserves further investigation.

Adult↗

Acute hemorrhagic cystitis. Industrial exposure to the pesticide chlordimeform.

An outbreak of hematuria occurred from May 20 to May 23, 1975, among employees of a chemical packaging plant. Nine of 22 workers who packaged the insecticide chlordimeform in a separate shed became severely ill with abdominal pain, dysuria, urgency to void, or hematuria. None of 18 persons who worked in other areas of the plant were affected. Four additional workers who had packaged the chemical during the previous year had a history of similar symptoms. Bladder biopsy specimens from three affected persons showed severe hemorrhagic cystitis; chlordimeform and 2-methyl-4-chloroaniline, a metabolite of chlordimeform, were present in urine specimens collected three days after exposure. The illness lasted from one week to two months; the workers recovered completely. Chlordimeform that was injected subcutaneously into three cats produced similar, though less severe, changes in the bladders of two animals.

Acute Disease↗

Hemorrhagic cystitis with MOPP therapy.

After 12 cycles of MOPP therapy for Hodgkin's Disease, an adolescent black male developed hemorrhagic cystitis, which clinically and histologically was similar to that induced by cyclophosphamide. At that time he had a normal platelet count and had never been irradiated below the diaphram. The markedly contracted bladder returned to normal approximately one month following cessation of therapy.

Child↗

Emphysematous cystitis due to Clostridium perfringens and Candida albicans in two patients with hematologic malignant conditions.

BACKGROUND: Fever, abdominal pain, and hematuria developed in two patients with hematologic malignant conditions (multiple myeloma and agnogenic myeloid metaplasia). Each patient was found to have emphysematous cystitis (EC), secondary to Clostridium perfringens and Candida albicans, respectively. Both patients had debilitated general medical conditions, compromised immune function, prior treatment with broad-spectrum antibiotics and corticosteroids, bladder outlet obstruction, and indwelling Foley catheters as predisposing factors to EC. Neither was diabetic. METHODS: These cases provide an opportunity to review the related medical literature on the pathophysiology and management of this uncommon entity. RESULTS: Treatment consists of control of underlying diabetes (if present), administration of appropriate antibiotics, establishment of urinary drainage, provision of supportive general medical care, exclusion of the presence of a bladder fistula, and surgical debridement only when unavoidable. CONCLUSIONS: EC should be part of the differential diagnosis in patients with cancer who have fever, abdominal pain, and hematuria.

Aged↗