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PubMed2005

Nerve growth factor mediates peripheral mechanical hypersensitivity that accompanies experimental cystitis in mice.

Increased sensitivity to somatic stimuli has been noted in the presence of visceral inflammation. Cystitis was induced by intraperitoneal injection of cyclophosphamide (CYP) in female mice. Sensitivity of hind paws to mechanical stimuli was determined prior to and 4, 9 and 24 h after CYP, and sensitivity of the tail to thermal stimuli was determined prior to, 4 and 24 h after CYP treatment. To investigate the role of nerve growth factor (NGF) in these processes, other groups of mice received NGF antiserum, normal serum, or K252a intravenously 30 min after CYP administration. CYP induced bladder inflammation that was not ablated by treatment with NGF antiserum or K252a. Sensitivity to mechanical stimuli was increased 4 and 9 h after CYP administration. This was reversed by NGF antiserum or K252a but not by normal serum. After 24 h, no differences were observed in withdrawal threshold among groups. None of the treatments had any effect on sensitivity to thermal stimuli. To further investigate the role of NGF in this process, NGF was instilled into the bladders of mice in the presence or absence of intravenous NGF antiserum. Four hours after intravesical instillation of NGF, the threshold of the hind paws to mechanical stimulation was significantly decreased, and this effect was reversed by prior treatment with NGF antiserum. This model of visceral pain causes increased sensitivity to peripheral application of mechanical stimuli. This effect is at least partially mediated by NGF, and the bladder may be the source of NGF in this process.

Animals↗
PubMed2005

Outcomes of a pharmacoepidemiological survey on the antibiotic treatment of uncomplicated acute cystitis in community.

We carried out a community-based survey in order to emphasize the importance of therapeutic appropriateness of antibiotic prescription by local physicians and the close connection between pharmacotherapy and pharmacoeconomics. Twenty general practitioners belonging to the local sanitary firm of Paola (CS, Italy) provided information, including their prescription, regarding 64 patients, both male and female, presenting clinical symptoms of uncomplicated acute cystitis. The data collected were compared with those of a previous trial performed in the same setting and documenting the effectiveness and advantages associated with the use of amoxicillin against community-acquired uncomplicated urinary tract infections (UTI). By comparing the prescriptive behaviour of physicians between the first and the present survey, we detected a significant increase in the use of amoxicillin (from 0 to 26.56%), paralleled by a decrease in prescribing aminoglycosides (from 18.18 to 1.56%). In addition, this resulted in a significant reduction in the costs of treatment (from 23.06 to 12.75 euros). Therefore, given the vast consensus concerning the adoption of empirical treatment for the eradication of UTI, the present survey underlines the crucial role of local antibiotic resistance monitoring in order to optimize the use of these drugs. Moreover, we have also observed a significant reduction in treatment costs associated with an appropriate and effective treatment of UTI.

Acute Disease↗
PubMed2004

Hemorrhagic adenovirus cystitis after renal transplantation.

PURPOSE: Viral infections are a major cause of postoperative morbidity and mortality after renal transplantation. Although cytomegalovirus, Epstein-Barr virus, and polyoma virus infections are common, there have been only a few reports of adenovirus infections. MATERIALS AND METHODS: We report an unusual case of a patient with adenovirus-induced hemorrhagic cystitis (AHC). We also performed a comprehensive MEDLINE review to identify similar cases. We then compared the presentation, management, and outcome of all patients to identify patterns that may facilitate the diagnosis and management of AHC. RESULTS: Review of the literature revealed 36 other reported cases of AHC in renal transplant recipients. Thirty-six of the 37 cases occurred within 1 year of transplantation. These patients presented with fever, dysuria, hematuria, and graft dysfunction. Thirty-four received high-dose steroids for treatment of symptoms of acute rejection. Four patients received antiviral medications. The infection was self-limited with mean duration of symptoms being 20 days. In all cases, serum creatinine returned to baseline or near baseline levels with resolution of symptoms. CONCLUSIONS: Although uncommon, AHC usually presents within 1 year of renal transplantation with a consistent constellation of symptoms. The infection appears to be self-limited with full recovery in most patients within 4 weeks. The efficacy of antiviral medications could not be determined in this review.

Adenoviridae Infections↗
PubMed2004

Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor in men with interstitial cystitis versus chronic pelvic pain syndrome.

OBJECTIVES: To determine whether men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have urine markers previously described for patients with interstitial cystitis (IC; presence of antiproliferative factor [APF] activity, decreased levels of heparin-binding epidermal growth factor-like growth factor [HB-EGF], and increased levels of epidermal growth factor). METHODS: Clean catch urine specimens were collected from 41 symptomatic patients with CP/CPPS, 36 asymptomatic men without bladder disease who served as the control group, and 24 men with IC. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and epidermal growth factor levels were determined by enzyme-linked immunosorbent assay. RESULTS: Men with CP/CPPS did not differ significantly from asymptomatic controls for any of the three markers tested (P >0.49). In contrast, APF activity was present significantly more often and HB-EGF levels were significantly lower in the urine specimens from men with IC than in the specimens from controls or patients with CP/CPPS (P <0.00001 for all four comparisons). Although the epidermal growth factor levels also tended to be higher in the urine from patients with IC than in the urine from controls, the difference did not reach statistical significance (P = 0.06). CONCLUSIONS: These findings indicate that at least two of the urine biomarkers previously identified in women with IC (presence of APF activity and decreased levels of HB-EGF) are also found in men with IC, but not in men with CP/CPPS. This finding suggests that IC and CP/CPPS may be two different disorders with distinct pathophysiologies. It also confirms the utility of the presence of APF activity and HB-EGF levels as markers for IC in men, as well as in women, with this disorder.

Adolescent↗
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↗
PubMed2004

Expression of intercellular adhesion molecules in the bladder of patients with interstitial cystitis.

OBJECTIVES: To study the presence of intercellular adhesion molecule-1 (ICAM-1), P-selectin, and E-selectin, as well as the cytoskeletal components talin and vinculin that bind to cellular adhesion molecules (CAMs), in bladder biopsies from patients with interstitial cystitis (IC) and controls. IC is a sterile, bladder disorder characterized by urinary frequency and pelvic floor pain. The pathologic bladder findings include defective urothelium, activated mast cells, and variable inflammation. Mast cells can induce the expression of CAMs necessary for initiation of inflammation. METHODS: Fresh frozen biopsies were analyzed immunocytochemically from 2 female normal bladders, 10 female IC bladders, 1 clear margin of transitional cell carcinoma of female bladder, 1 normal foreskin, 1 transitional cell carcinoma of foreskin, and 1 inflamed male finger. RESULTS: Of the 10 IC samples, 9 were positive for ICAM-1, 6 for P-selectin, 6 for vinculin, 5 for talin, and 4 for E-selectin, all exclusively perivascular. Both normal bladders were negative for ICAM-1 and P-selectin and faintly positive for E-selectin, and one was weakly positive for talin and vinculin; the normal foreskin was negative. The "control" samples from the transitional cell carcinoma of the bladder and foreskin, as well as the inflamed finger skin, were positive only for ICAM-1. An increased number of activated mast cells associated with ICAM-1 was noted in IC. CONCLUSIONS: These results showed that ICAM-1 is expressed in IC, with variable expression of the other markers studied, supporting the different degrees of bladder inflammation noted in patients with IC.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2004

Encrusted cystitis and pyelitis in children: an unusual condition with potentially severe consequences.

OBJECTIVES: To report our experience with the management of encrusted cystitis and pyelitis (EC and EP) in the pediatric population. EC and EP are well-known entities in adults but are rarely identified in children. They consist of mucosal encrustations and are due to specific microorganisms. METHODS: Between 1996 and 2001, 4 children with a mean age of 9 years (range 4 to 13) were treated for EC (n = 2), EP (n = 1), and EC and EP (n = 1). The latter was a kidney transplant recipient. We retrospectively evaluated the clinical characteristics of the patients and the results of conservative management. RESULTS: The delay between the beginning of the symptoms and the diagnosis was longer than 1 month in all cases. The diagnosis of EC was not evoked and was made during cystoscopy in all cases. EP was diagnosed during pyelotomy in 1 patient because it was evoked and confirmed by computed tomography scan in the kidney transplant recipient. Corynebacterium urealyticum was identified in the urine of all patients. EC was treated by antibiotics and endoscopic debulking, and EP was treated by antibiotics and local acidification. The duration of antibiotic therapy was between 1 and 6 months. The tolerance to local acidification of the kidneys was poor. Cure was achieved in 3 cases, but the treatment of EP failed in the kidney transplant recipient and graft removal was decided after 6 months of failed management because intractable febrile urinary tract infections became life threatening for the patient. CONCLUSIONS: EC and EP are uncommon in children; however, these diseases must be considered. They must be diagnosed rapidly and require, if possible, conservative management. Nevertheless, kidney loss can occur in transplant recipients with EP.

Adolescent↗
PubMed2004

Prevalence of interstitial cystitis in young women.

OBJECTIVES: Traditional epidemiologic studies have significantly underestimated interstitial cystitis (IC) prevalence because they surveyed populations for diagnosed cases rather than screening for IC symptoms and evaluating suspected cases. Our earlier data have suggested that IC affects almost 25% of women. To test this hypothesis, we used a validated IC symptom questionnaire and intravesical potassium sensitivity testing (PST), history, and physical examination to determine the prevalence of IC in a fixed population of young women. METHODS: All female members of the University of California, San Diego, third-year medical student class were asked to complete the Pelvic Pain and Urgency/Frequency (PUF) scale. All those scoring 7 or greater were asked to undergo clinical evaluation, including urinalysis, urine culture, and PST. RESULTS: Of 52 potential subjects, 49 (median age 26 years) completed the PUF scale. Of the 49, 15 (30.6%) scored 7 or greater; 5 of those 15 volunteered for PST. All 5 had negative urinalysis findings and were PST positive, for a 10% (5 of 52) rate of positive voluntary PST in the medical student population. All 15 subjects with PUF scores of 7 or greater reported being sexually active. Dyspareunia was present in 13 (87%) of the 15 women, including all 5 PST-positive subjects. CONCLUSIONS: We identified probable IC in 30.6% and documented IC in a minimum of 10% of the female medical students. These data suggest the estimate of IC prevalence in the United States should be vastly increased from approximately 1.5 million to perhaps 25 to 30 million women and that IC is highly prevalent in young women. Screening for IC-specific symptoms is a useful method for identifying undiagnosed IC cases.

Adult↗
PubMed2005

Cystoprostatectomy and neobladder construction for florid cystitis glandularis.

Cystitis glandularis is a benign proliferative disease of the bladder mucosa with a characteristic histopathologic appearance. If a mass lesion is identified, it is resected transurethrally. More extensive surgical management for severe or recurrent cases is poorly characterized in published studies. We present a patient with multiple rapid recurrences of polypoid masses on the trigone causing irritative voiding symptoms. He developed a low-compliance small-capacity bladder and bilateral ureteral obstruction. The patient underwent total cystoprostatectomy with cavernosal nerve sparing and ileal neobladder construction. We advocate such aggressive surgical management in select cases of this disease.

Adenoma, Villous↗
PubMed2005

Successful downregulation of bladder sensory nerves with combination of heparin and alkalinized lidocaine in patients with interstitial cystitis.

OBJECTIVES: To test the efficacy of a new intravesical therapeutic solution in relieving urgency/frequency and pain in interstitial cystitis (IC). METHODS: A solution of 40,000 U heparin, 8 mL 1% lidocaine (80 mg; group 1) or 2% lidocaine (160 mg; group 2), and 3 mL 8.4% sodium bicarbonate was administered intravesically in patients with newly diagnosed IC with significant frequency, urgency, and pain. Using the Patient Overall Rating of Improvement of Symptoms, the response to treatment was evaluated within 20 minutes of instillation in all patients, after 24 to 48 hours in group 2, and after three treatments per week for 2 weeks in group 2 patients who elected to receive additional instillations. Significant symptom relief was defined as 50% or greater symptom improvement. RESULTS: After one instillation, 35 (75%) of 47 patients in group 1 (1% lidocaine) and 33 (94%) of 35 in group 2 (2% lidocaine) reported significant immediate symptom relief. The difference in the response rates was statistically significant (P <0.01). In group 2, 50% of the subjects experienced at least 4 hours of symptom relief from the single instillation, and 16 (80%) of 20 reported significant sustained symptom relief after 2 weeks of treatment. CONCLUSIONS: Intravesical treatment with combined heparin and alkalinized lidocaine immediately reduced the pain and urgency of IC in most patients treated for newly diagnosed IC. Symptom relief lasted beyond the duration of the local anesthetic activity of lidocaine, suggesting the solution suppresses neurologic upregulation. In IC treatment, this new intravesical solution may be helpful in the interval before heparinoid therapy reaches its full effect.

Administration, Intravesical↗
PubMed2006

Prevalence of benign microscopic hematuria among women with interstitial cystitis: implications for evaluation of genitourinary malignancy.

OBJECTIVES: To assess the prevalence of benign microscopic hematuria among a cohort of women with clinical interstitial cystitis (IC). METHODS: A total of 100 women were prospectively assessed for microscopic hematuria with postvoid sterile catheterization. The evaluation for all patients included urine culture, potassium sensitivity test (PST), cystoscopy with hydrodistension under general anesthesia, and symptom assessment with the Pelvic Pain and Urgency/Frequency (PUF) questionnaire. RESULTS: The mean age +/- SD was 37 +/- 15 years, with no difference noted in those with or without microscopic hematuria (P = 0.71). Microscopic hematuria was present in 24 (24%) of the 100 women. No patient had gross hematuria, positive urine culture, or cystoscopic findings suspicious for malignancy. The mean PUF score was 17 +/- 6. The PST was positive in 92 (92%) of 100 women, and 8 patients had only cystoscopic findings diagnostic of IC. The likelihood of a positive PST or positive cystoscopic findings among patients with microscopic hematuria was similar to that of patients without microscopic hematuria. The PST results correlated with the cystoscopic findings (P < 0.001). Of 36 patients with positive cystoscopic findings, 28 (78%) had a positive PST, and 28 (30%) of 92 with a positive PST had positive cystoscopy findings. CONCLUSIONS: In this cohort of women with IC, the prevalence of benign microscopic hematuria was 24%. These data suggest that in women at low risk of genitourinary malignancy who have clinical IC, microscopic hematuria may be an incidental finding.

Adult↗
PubMed2000

Diagnosis, treatment, and lifestyle changes of interstitial cystitis.

Interstitial cystitis (IC) is a chronic inflammation of all the layers of the bladder wall. As it is difficult to diagnose and it affects mostly women, many physicians misdiagnose it as a psychological problem. Almost half a million individuals in the United States suffer from this cureless disorder. This article will review the anatomy, physiology, etiology, diagnosis, treatments, and current research foci of IC, along with the effects of the disease on lifestyle and personal issues from the patient's perspective.

Adult↗
PubMed2003

[Bladder fibrosis caused by eosinophilic cystitis].

A 70-years-old man with no history of allergy or genitourinary problems had bilateral hydronephrosis, a marked decrease in bladder capacity and severe eosinophilic infiltration with fibrosis of the bladder wall. A total cystoprostatectomy with ileal bladder replacement was performed. We reviewed the literature of eosinophilic cystitis for clinical presentation, diagnosis and therapeutic options.

Aged↗
PubMedDate not supplied

The relationship between fibromyalgia and interstitial cystitis.

Interstitial cystitis (IC) is a relatively uncommon and enigmatic disorder characterized by pain in the bladder and pelvic region, typically accompanied by urinary urgency and frequency. Fibromyalgia is a more common disorder, with the prominent symptoms being diffuse musculoskeletal pain and fatigue, and it has been well established that there is substantial clinical overlap between fibromyalgia and chronic fatigue syndrome (CFS). Although genitourinary and musculoskeletal symptoms predominate in IC and fibromyalgia respectively, both disorders share a number of features, including similar demographics, "allied conditions" (e.g. irritable bowel syndrome, headaches, etc.), natural history, aggravating factors, and efficacious therapy. We hypothesized that there was substantial clinical overlap between fibromyalgia and IC, and examined cohorts of individuals with these two disorders in parallel, to compare the spectrum of symptomatology. Sixty fibromyalgia patients, 30 IC patients, and 30 age-matched healthy controls were questioned regarding current symptomatology. A dolorimeter examination was also performed in the three groups to assess peripheral nociception. We found that the frequency of current symptoms was very similar for the fibromyalgia and IC groups. Both the fibromyalgia and IC patients displayed increased pain sensitivity when compared to healthy individuals, at both tender and control points. These data suggest that IC and fibromyalgia have significant overlap in symptomatology, and that IC patients display diffusely increased peripheral nociception, as is seen in fibromyalgia. Although central mechanisms have been suspected to contribute to the pathogenesis of fibromyalgia for some time, we speculate that these same types of mechanisms may be operative in IC, which has traditionally been felt to be a bladder disorder.

Adult↗
PubMed1998

Increased tyrosine hydroxylase immunoreactivity in the locus coeruleus of cats with interstitial cystitis.

PURPOSE: Environmental stressors seem to play a role in exacerbation of symptoms of interstitial cystitis (IC), both in cats and in human beings. These observations suggest a role for the sympathetic nervous system in the pathophysiology of IC. To begin to assess the underlying role in IC of the pontine nucleus locus coeruleus (LC), the most important source of norepinephrine in the central nervous system, we compared the intensity of tyrosine hydroxylase immunoreactivity (THIR) in sections of LC obtained from cats with IC and from healthy cats. Cats with IC were studied during quiescent periods in an attempt to avoid the risk of flare-induced activation of the LC. MATERIALS AND METHODS: Six cats diagnosed with IC and six healthy cats were studied. Cats with IC were monitored to ensure that no behavioral or urinary signs attributable to IC had been observed for at least two weeks prior to the study. Cats were euthanized and perfused with 4% paraformaldehyde, after which brainstem tissues were collected. Coronal sections (10 microns) of LC were prepared and examined for THIR. RESULTS: THIR in total LC, parabrachial nucleus and LC complex was significantly greater (p < 0.05) in samples from cats with IC than from healthy cats. CONCLUSIONS: The increased THIR in the LC of cats with IC provides additional evidence for increased sympathetic nervous system activity in patients with IC, even during periods of absence of clinical signs.

Animals↗
PubMed1998

Polymerase chain reaction amplification of bacterial 16S rRNA genes in interstitial cystitis and control patient bladder biopsies.

PURPOSE: Several characteristics of the chronic bladder disease called interstitial cystitis (IC) suggest an infectious etiology. However, a single causative organism has not been convincingly cultured in vitro, and DNA for a variety of microorganisms has been found inconsistently in bladder biopsies from IC patients. We therefore looked for a possible bacterial cause for IC by using a sensitive nested PCR assay on cystoscopic bladder biopsy specimens obtained from IC patients and controls. MATERIALS AND METHODS: Bladder biopsies were obtained at cystoscopy from 6 IC patients and 6 controls. DNA was extracted from these specimens and PCR with 2-round amplification performed using nested primers from a highly conserved region of the bacterial 16s rRNA gene. Amplified DNA was purified and sequenced using the Sequenase PCR Product Sequencing Kit, and the sequences obtained were compared with bacterial rRNA gene sequences recorded in GenBank. RESULTS: Biopsy specimens from all 6 patients and 6 controls were positive by PCR for DNA encoding bacterial 16s rRNA. Sequence data indicated a predominant microorganism in 10 of the 12 specimens, with > 95% homology to DNA from several different genera of bacteria including Acinetobacter, Propionobacterium, Salmonella, and Escherichia. None of the organisms identified by PCR had been cultured from tissue or urine obtained simultaneously from these persons, using sensitive culture techniques. CONCLUSIONS: These data indicate no difference between IC patients and controls in the proportion of bladder biopsies with PCR positivity or the type(s) of organism present, providing additional evidence that IC is not associated with infection by a particular type of bacterium.

Cystitis, Interstitial↗