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PubMed2000

CNS induced neurogenic cystitis is associated with bladder mast cell degranulation in the rat.

PURPOSE: To determine if bladder mast cell degranulation is involved in the genesis of neurogenic cystitis induced by pseudorabies virus (PRV) invasion of the central nervous system (CNS). MATERIALS AND METHODS: Rats received a total of 4 x 106 plaque forming units (pfu) of PRV-Bartha in the abductor caudalis dorsalis (ACD) muscle. Granulated bladder mast cells per mm2 of bladder tissue and urine histamine content were monitored as the cystitis developed over the next few days. In a subgroup of rats, intravesical resiniferatoxin was used to remove capsaicin-sensitive sensory bladder afferents, while another subgroup was pretreated with a mast cell degranulator. RESULTS: PRV injection into the ACD muscle leads to neurogenic cystitis. Histamine levels were elevated in the urine of virus injected rats before any behavioral or microscopical signs of cystitis were present. When the cystitis became clinically manifest, urine histamine returned to control levels, and the number of granulated mast cells dropped significantly. Rats in which capsaicin-sensitive afferents had been removed did not show any signs of cystitis, or increase in urine histamine, or change in the number of granulated mast cells. Pretreatment of animals with a mast cell degranulator completely prevented the appearance of cystitis without altering the CNS disease. CONCLUSION: These results provide further evidence that mast cells are involved in neurogenic cystitis induced by changes in CNS activity.

Administration, Intravesical↗
PubMed2001

Increased plasma norepinephrine concentration in cats with interstitial cystitis.

PURPOSE: Interstitial cystitis is a chronic urological syndrome affecting humans and domestic animals, including cats (feline interstitial cystitis). The symptoms of interstitial cystitis seem to be exacerbated by stress, suggesting involvement of the sympathetic nervous system and/or hypothalamic-pituitary-adrenal axis. Others have described sympathetic nervous system abnormalities in patients with interstitial cystitis but to our knowledge no data on plasma catecholamine concentrations or hypothalamic-pituitary-adrenal axis function in such patients have been reported. To evaluate the role of these systems in cats with feline interstitial cystitis we simultaneously measured baseline plasma concentrations of catecholamines and their metabolites to assess sympathetic activity, and the response of plasma adenocorticotropic hormone and cortisol concentrations to the infusion of corticotropin-releasing factor. MATERIALS AND METHODS: Eight healthy cats and 8 with feline interstitial cystitis were anesthetized and a catheter was placed in the external jugular vein. Four hours after recovery samples were obtained for high performance liquid chromatography analysis of plasma norepinephrine, dihydroxyphenylglycol, epinephrine, dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid. In 4 cats per group 1 microg. ovine corticotropin-releasing factor per kg. body weight was infused and blood samples were collected at intervals for 120 minutes for determining adenocorticotropic hormone and cortisol. RESULTS: Significant increases in plasma norepinephrine and dihydroxyphenylglycol as well as a trend toward increased epinephrine were found, whereas no effect on dihydroxyphenylalanine, dopamine, dihydroxyphenylacetic acid, adenocorticotropic hormone or cortisol was identified in cats with feline interstitial cystitis. CONCLUSIONS: These results support and extend previous studies identifying an increase in sympathetic activity in cats with feline interstitial cystitis.

Animals↗
PubMed2002

Changes in urinary bladder cytokine mRNA and protein after cyclophosphamide-induced cystitis.

Cyclophosphamide (CYP)-induced cystitis alters micturition function and produces reorganization of the micturition reflex. This reorganization may involve cytokine expression in the urinary bladder. These studies have determined candidate cytokines in the bladder that may contribute to the reorganization process. An RNase protection assay was used to measure changes in rat bladder cytokine mRNA [interferon-gamma (IFN)-gamma, interleukin-1alpha/beta (IL-1alpha/beta), IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, and tumor necrosis factor-alpha/beta (TNF-alpha/beta)] after acute (4 h), intermediate (48 h), or chronic (10 day) cystitis. The correlation between bladder cytokine mRNA and protein expression was also determined by immunoassay. Although at each time point after cystitis significant changes in bladder cytokine mRNA were observed, the magnitude differed (acute > intermediate > chronic). Acute cystitis demonstrated the most robust changes (P </= 0.005; IL-1beta, 330-fold increase; IL-2, 20-fold increase; IL-4, 8-fold increase; IL-6, 80-fold increase) in cytokine mRNA expression and TNF-alpha or TNF-beta mRNA were only increased (2-10-fold) after acute cystitis. More modest increases in cytokine mRNA expression were observed after 48-h or 10-day cystitis. Cytokine protein expression generally paralleled that of mRNA. Increased cytokine expression after CYP-induced cystitis, alone or in combination with other inflammatory mediators or growth factors, may contribute to altered lower urinary tract function after cystitis.

Acrolein↗
PubMed1999

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

PURPOSE: We 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. MATERIALS AND METHODS: Bladder 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. RESULTS: In 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. CONCLUSIONS: Bladder 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.

Adult↗
PubMed2000

Increased tyrosine hydroxylase immunoreactivity in bladder tissue from patients with classic and nonulcer interstitial cystitis.

PURPOSE: Interstitial cystitis is a chronic debilitating condition which mainly affects women. Accumulated evidence indicates that interstitial cystitis is a heterogeneous syndrome. The nonulcer subtype appears different than classic interstitial cystitis in regard to symptoms, and endoscopic and histological findings as well as response to various treatments. We further explore the neurogenic nature of this disease using indirect immunofluorescence to evaluate the presence and density of various autonomic and sensory nerve fibers. MATERIALS AND METHODS: Specimens from the bladder wall of 6 patients with classic interstitial cystitis, 7 with nonulcer interstitial cystitis and 6 controls were evaluated to determine the presence and density of nerve fibers containing tyrosine hydroxylase, calcitonin gene-related peptide, neuropeptide Y and substance P using specific antibodies, and the general presence of nerve fibers using a mixture of antibodies against nerve filament, neuron specific enolase and S-100 protein. RESULTS: Increased density and number of nerve fibers immunoreactive for tyrosine hydroxylase were noted in interstitial cystitis cases compared to controls. Furthermore, there was a difference between classic and nonulcer disease in the overall density of nerves using the antibody mixture. CONCLUSIONS: Our findings indicate an altered peripheral sympathetic innervation in interstitial cystitis cases, which may be an indication of primary neurogenic etiology. The difference in nerve density observed after incubation with the antibody mixture between classic and nonulcer interstitial cystitis supports the hypothesis that the 2 forms represent separate entities.

Adult↗
PubMed2000

Quality of life among women with interstitial cystitis.

PURPOSE: Clinical case series suggest that the impact of interstitial cystitis on quality of life is severe and debilitating, however, little epidemiologic information is available. We examined the impact of interstitial cystitis on quality of life in a population based cohort of United States women. MATERIALS AND METHODS: We collected multidimensional measures of quality of life from 159,419 participants in the Nurses' Health Study I and II using a validated instrument, the Medical Outcome Study Short-Form 36 Health Survey Instrument. This instrument measures physical function, role limitations due to physical and emotional problems, bodily pain, vitality, social function and mental health. Quality of life measures were collected on 99 women with prevalent self reported interstitial cystitis confirmed by medical record review. RESULTS: After adjusting for age and co-morbid conditions, women with interstitial cystitis had significantly lower quality of life scores in 4 of the 7 quality of life dimensions, including role/physical (beta -13.1, p <0.001), bodily pain (beta -9.8, p <0.001), vitality (beta -7.7, p <0.001) and social function (beta -7.2, p <0.001) compared to women without interstitial cystitis. Women with interstitial cystitis experienced less decrement in physical function compared to women with rheumatoid arthritis but more compared to women with hypertension. In addition, they experienced greater differences in vitality and mental health than women with rheumatoid arthritis or hypertension. CONCLUSIONS: The quality of life among women with interstitial cystitis was especially limited in the psychosocial dimensions, such as vitality and mental health. Future research on interstitial cystitis should incorporate multidimensional measures of quality of life, especially with respect to response to the various treatments.

Adult↗
PubMed2002

Norepinephrine content and adrenoceptor function in the bladder of cats with feline interstitial cystitis.

PURPOSE: Interstitial cystitis is a chronic syndrome affecting humans and domestic animals, including cats (feline interstitial cystitis). The aggravation of interstitial cystitis symptoms by stress suggests involvement of the sympathetic nervous system. Studies have identified increased sympathetic nervous system activity in patients with interstitial cystitis but to our knowledge effects on bladder function have not been reported. To address this question we measured bladder norepinephrine (NE) content, the electrical field stimulation flux of NE and acetylcholine (ACh), and the effects of feline interstitial cystitis on adrenoceptor (AR) mediated bladder strip contractility. MATERIALS AND METHODS: Bladders were obtained from healthy cats and cats with feline interstitial cystitis. In experiment 1 bladder tissue NE content was determined and the simultaneous release of 3H-NE and 14C-ACh in perfusion bath effluent after electrical field stimulation was measured. NE and ACh release was calculated from the area under the efflux curve. In experiment 2 electrical field stimulation induced contractility of bladder body strips was measured in the presence of 100 nM. to 25 microM. NE only or combined with atipamezole (an alpha2-AR antagonist), propranolol (a beta-AR antagonist) or phentolamine (an alpha-AR antagonist). Antagonists were added to the bath at least 15 minutes before stimulation, after which NE was added in cumulative doses and dose response curves were constructed. RESULTS: Significant increases in NE content and efflux in the absence of alterations in ACh efflux were identified. In the bladder strip studies decreased alpha2 and beta1-AR function was found in strips from cats with feline interstitial cystitis, whereas beta3 or atypical beta-ARs were tentatively identified. CONCLUSIONS: These results support and extend previous studies by identifying an effect of increased sympathetic activity on bladder function in cats with feline interstitial cystitis.

Animals↗
PubMedDate not supplied

[Physiopathologic relationship between interstitial cystitis and rheumatic, autoimmune, and chronic inflammatory diseases].

OBJECTIVES: To evaluate the current knowledge about interstitial cystitis pathophysiology and its relationship with rheumatic, autoimmune and chronic inflammatory diseases. METHODS: Literature search under "interstitial cystitis pathophysiology" either clinical or experimental trials and reports, in Medline, PubMed, Digital Urology Journal and Doctor's Guide, in addition to our own clinical research experience results. RESULTS: Both human and experimental trials show resemblances between interstitial cystitis and rheumatic, autoimmune, and chronic inflammatory diseases on clinical presentations, pathophysiology. Some interstitial cystitis patients show the bladder infiltrated with specific mononuclear cells, high incidence of circulating antinuclear antibodies, good response to anti-inflammatory and/or immunosuppressive therapies. Interstitial cystitis in association with rheumatic, autoimmune and chronic inflammatory diseases is very common. Many patients with systemic lupus erythematosus, Sjögren syndrome and fibromyalgia syndrome show antibodies against urothelium and/or muscle cells and/or other connective tissue components of urinary bladder. Systemic lupus erythematosus and Sjögren syndrome are the autoimmune diseases which bear strongest similarity with interstitial cystitis. Moreover, rheumatoid arthritis, chronic pelvic pain syndrome, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, Evan's syndrome and atopic dermatitis share some pathogenic characteristics. CONCLUSIONS: Nowadays, interstitial cystitis pathophysiology is unknown. Based on clinical presentations, epidemiology, pathology and laboratory findings and treatment response, there is an important correlation among interstitial cystitis and rheumatic, autoimmune and chronic inflammatory diseases. These disorders may share some pathophysiologic mechanisms. Rigorous studies of pathophysiology of these group of diseases are needed to confirm consistently this approach for such conditions.

Autoimmune Diseases↗
PubMed1991

[Clinical studies on acute uncomplicated cystitis in women].

A total of 499 female patients with acute uncomplicated cystitis were observed and analyzed clinically for age distribution, characteristics of symptoms, bacterial culture of urine, behavioral aspects of recurrent cystitis and others. The patients were between 3 years and 88 years old (average: 43 years) and the majority of patients were from 20 to 69 years old. From 81.1% of the patients Escherichia coli was detected, followed by Staphylococcus spp (11.2%). The major symptoms were pain on urination (421 cases), urinary frequency (421 cases) and residual urine sensation (418 cases). The major causes of cystitis as reported by the patient were fatigue (131 cases), infrequent voiding (114 cases) and exposing the body to coldness (103); only 42 patients reported a relationship between sexual intercourse and cystitis. The patients who had been suffering from "honeymoon cystitis" were significantly inclined to be suffering from acute uncomplicated cystitis again in comparison with those who had not suffered from honeymoon cystitis. There was suggested to be a relationship between sexual intercourse and recurrent cystitis.

Acute Disease↗
PubMed1986

Hemorrhagic cystitis associated with adenovirus infection in bone marrow transplantation.

A retrospective study of bone marrow transplant recipients shedding adenovirus type 11 in the urine was carried out to determine the association between viral shedding and hemorrhagic cystitis in this population. Weekly urine virology surveillance cultures were obtained during the first 100 days following transplantation. Adenovirus type 11 was cultured from five of 502 bone marrow transplant recipients from 1977 through 1984. In four of these five patients there was associated hemorrhagic cystitis. This contrasts with an overall incidence of hemorrhagic cystitis of 20% in this bone marrow transplant population. A case of hemorrhagic cystitis occurred in a patient following bone marrow transplantation. Recognition of a viral origin of hemorrhagic cystitis may explain the occurrence of late hemorrhagic cystitis in patients despite interventions designed to prevent cyclophosphamide-induced hemorrhagic cystitis. Hemorrhagic cystitis may be the presenting sign of a lethal adenoviral infection.

Adenoviridae Infections↗
PubMed1984

Hemorrhagic cystitis after conditioning for bone marrow transplantation and its prophylaxis.

The situation regarding hemorrhagic cystitis after conditioning for bone marrow transplantation (BMT) in Japan was surveyed and analyzed. Thirty-seven of 110 patients (33.6%) developed hemorrhagic cystitis after conditioning for BMT with cyclophosphamide (CY) and total body irradiation. In two of these 37 patients the cystitis was virus (adenovirus)-induced. In the others it was diagnosed as CY-induced. The severity and duration of CY-induced hemorrhagic cystitis were related to its onset. The delayed type of hemorrhagic cystitis induced by CY seemed to have a poor prognosis and often continued until the patient died. Therefore, late-onset hemorrhagic cystitis should be followed carefully and its prophylaxis may be important. 2-Mercaptoethane sulphonate (mesna) injections for prophylaxis of CY-induced hemorrhagic cystitis were found to be effective in reducing the incidence of the delayed type in 21 (53.8%) of 39 patients treated, but did not reduce the total incidence of CY-induced hemorrhagic cystitis.

Bone Marrow Transplantation↗
PubMed1993

Hemorrhagic cystitis associated with allogeneic and autologous bone marrow transplantation for malignant neoplasms in adults.

We investigated the occurrence of hemorrhagic cystitis in 30 consecutive adult patients undergoing bone marrow transplantation (BMT) for hematological and non-hematological malignancies. Ten patients with hematological malignancies received allogeneic BMT, and twenty patients, seven with hematological and 13 with non-hematological malignancies, received autologous BMT. All 30 patients received high-dose cyclophosphamide-containing regimens (120 mg/kg in 16, 200 mg/kg in one, 6000 mg/m2 in 13) as preparative therapies. They all received 2-mercaptoethane sulphonate sodium (mesna) combined with hyperhydration 3 liter/day as prophylaxis for hemorrhagic cystitis. Bladder irrigation was not performed. Overall, five patients (16.7%) developed hemorrhagic cystitis; early-onset (within 48 hours of the end of the high dose chemoradiotherapy) hemorrhagic cystitis occurred in one (3.3%; 95% confidence interval, 0.6-16.7%) and late-onset occurred in four (13.3%; 95% confidence interval, 5.3-29.7%). In three of the four late-onset cases, adenovirus was isolated from the urine specimens at the onset of the hemorrhagic cystitis. Among the 13 patients with non-hematological malignancies receiving autologous BMT, one with recurrent breast cancer developed late-onset hemorrhagic cystitis associated with adenovirus type 11. We conclude the prophylactic measure with mesna and hyperhydration to be effective enough to prevent cyclophosphamide-induced hemorrhagic cystitis of early onset. Some BMT recipients, however, even those with non-hematological malignancies undergoing autologous BMT, develop late-onset hemorrhagic cystitis in which adenovirus is considered a principal causative agent.

Adult↗
PubMed1999

Epidemiology of interstitial cystitis: a population based study.

PURPOSE: Interstitial cystitis is a chronic and debilitating syndrome but surprisingly little is known about its epidemiology. This study was designed to estimate the prevalence of interstitial cystitis among women in the United States. MATERIALS AND METHODS: Female participants in the Nurses' Health Study (NHS) I and II (184,583) were asked by mailed questionnaires whether they had ever been diagnosed with interstitial cystitis. We requested and reviewed medical records of women self-reporting interstitial cystitis. The accuracy of self-reports was evaluated using standardized criteria. RESULTS: Among the 93,428 women who responded to the NHS II questionnaire and 91,155 women who responded to the NHS I questionnaire 1,354 (1.4%) and 357 (0.4%), respectively, self-reported interstitial cystitis. Based on medical record review 63 cases of interstitial cystitis were confirmed in NHS II and 47 in NHS I. The prevalence of interstitial cystitis was 67/100,000 women in NHS II and 52/100,000 in NHS I. There was no substantial variation in prevalence by age. CONCLUSIONS: The prevalence of interstitial cystitis in the United States is more than 50% greater than previously reported and 3-fold greater than that reported in Europe.

Adult↗
PubMed1990

Nerve fibre proliferation in interstitial cystitis.

The aetiology of pain in interstitial cystitis is not understood, although it has been reported to be due to release of mediators from mast cell granules. Cystolysis and intravesical instillation of dimethyl sulphoxide have been shown to relieve pain in this condition. We have studied the nerve population within the bladder wall using immunohistochemical stains for protein gene product 9.5. A group of 18 cases of chronic interstitial cystitis and 12 controls; neuropathic bladder (n = 1), chronic bacterial cystitis (n = 3), systemic lupus erythematosus cystitis (n = 2) and normals (n = 6), were investigated. There were significantly more nerve fibres within the sub-urothelial and detrusor muscle layers in chronic interstitial cystitis than there were in normals. Patients with chronic cystitis of other aetiology did not have a significant increase in nerve fibre density within the bladder wall suggesting a specific association between nerve fibre proliferation and interstitial cystitis. Cystolysis is shown to deplete selectively the submucosal nerve plexuses without altering the nerve density within detrusor muscle. This finding explains the desensitisation of the bladder without impairment of detrusor function after this procedure.

Cell Division↗
PubMed2006

Changes in galanin immunoreactivity in rat micturition reflex pathways after cyclophosphamide-induced cystitis.

Alterations in the expression of the neuropeptide, galanin, were examined in micturition reflex pathways of rat after cyclophosphamide (CYP)-induced cystitis of variable duration: acute (4 h), intermediate (48 h), or chronic (10 days). In control animals, galanin expression was present in specific regions of the gray matter in the rostral lumbar and caudal lumbosacral spinal cord, including: (1) the dorsal commissure (DCM); (2) superficial dorsal horn; (3) the regions of the intermediolateral cell column (L1-L2) and the sacral parasympathetic nucleus (SPN, L6-S1); and (4) the lateral collateral pathway (LCP) in lumbosacral spinal segments. Densitometry analysis demonstrated significant decreases (P< or =0.01) in galanin immunoreactivity (IR) in these regions of the L1-S1 spinal cord after acute or intermediate CYP-induced cystitis. In contrast, increases (P< or =0.01) in galanin-IR were observed in the DCM, SPN, or LCP regions in the L6-S1 spinal segments in rats with chronic cystitis. No changes in the number of galanin-immunoreactive cells were observed in the L1-S1 dorsal root ganglia (DRG) after CYP-induced cystitis of any duration. A small percentage of bladder afferent cells (Fast-blue-labeled) in the DRG expressed galanin-IR in control rats; this was not altered with cystitis. Galanin-IR was observed encircling DRG cells after chronic cystitis. These changes may contribute to urinary bladder dysfunction, altered sensation, and referred somatic hyperalgesia after cystitis.

Afferent Pathways↗
PubMed2006

Safety and efficacy of hyperbaric oxygen therapy for the treatment of interstitial cystitis: a randomized, sham controlled, double-blind trial.

PURPOSE: We conducted a double-blind, sham controlled study to evaluate the safety, efficacy and feasibility of hyperbaric oxygenation for interstitial cystitis. MATERIALS AND METHODS: A total of 21 patients with interstitial cystitis were randomized to 90 minutes treatment in a hyperbaric chamber pressurized with 100% O2 to 2.4 atmosphere absolute for 30 treatments sessions or 1.3 atmosphere absolute, breathing normal air in the control group. Moderate or marked improvement in a global response assessment questionnaire was defined as treatment response (primary outcomes). Secondary measurements included changes of pain and urgency evaluated by visual analog scales, functional bladder capacity and frequency. Changes in the O'Leary-Sant Interstitial Cystitis Index and rating of overall satisfaction with the therapeutic outcome were also reported. RESULTS: There were 3 of 14 patients on verum and no control patients who were identified as responders (p < 0.52) [corrected] At 12-month followup 3 patients (21.4%) still reported treatment response. Hyperbaric oxygenation resulted in a decrease of baseline urgency intensity from 60.2 +/- 15.0 to 49.9 +/- 35.2 mm at 3 months and decrease of pain intensity from 43.1 +/- 20.5 to 31.2 +/- 19.8 mm, respectively (p < 0.05). The Interstitial Cystitis Symptom Index score sum decreased from 25.7 to 19.9 points in patients on verum. Sham treatment did not result in improvement of the baseline parameters. CONCLUSIONS: A total of 30 treatment sessions of hyperbaric oxygenation appear to be a safe, effective and feasible therapeutic approach to interstitial cystitis. In the treatment responders application of hyperbaric oxygenation resulted in a sustained decrease of interstitial cystitis symptoms with a discordant profile regarding the peak amelioration of the various interstitial cystitis symptoms compared with a normobaric, normoxic sham treatment.

Adult↗
PubMed1998

The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis.

PURPOSE: We determined whether intravesical potassium absorption in normal bladders correlates with increased sensory urgency, and corroborated the hypothesis that mucus is important in the regulation of epithelial permeability. We compared sensory nerve provocative ability of sodium versus potassium, and determined whether intravesical potassium sensitivity discriminates patients with interstitial cystitis from normal subjects and those with other sensory disorders of the bladder. MATERIALS AND METHODS: A total of 231 patients with interstitial cystitis and 41 normal subjects underwent intravesical challenge with 40 ml. water and then 40 ml. of 40 mEq./100 ml. potassium chloride. Subjective responses of urgency or pain stimulation were recorded on a scale of 0 to 5. In 19 normal subjects potassium absorption was measured at baseline, after injury of the bladder mucus with protamine, after heparin treatment to reverse mucus damage and then for a final time. These subjects simultaneously recorded the symptoms of sensory urgency and pain at baseline, after protamine and after heparin. Another group of normal volunteers underwent a challenge with sodium versus potassium to determine which cation was more provocative. Patients with bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), detrusor instability, and acute and chronic urinary tract infection but no current infection were also evaluated for potassium sensitivity. RESULTS: Neither normal subjects nor patients with interstitial cystitis reacted to water administered intravesically. There was marked sensitivity to intravesical potassium in 75% of patients with interstitial cystitis versus 4% of controls (p <0.01). Only 1 patient with BPH responded to potassium and none of the 5 with chronic urinary tract infection responded. All 4 patients (100%) with a current acute urinary tract infection reacted positively to the potassium challenge. Of 16 patients with detrusor instability 25% responded. Normal subjects had minimal sensitivity to potassium before (11%) and markedly increased sensitivity after (79%) protamine treatment, and these symptoms were reversed by heparin in 42%. Potassium absorption directly correlated with symptoms (0.4, 3.0 and 1.3 mEq. before and after protamine, and after heparin reversal, respectively). In regard to sodium versus potassium provocation, potassium was far more provocative for causing urgency after protamine (10 versus 90%). Neither group underwent provocation before protamine. CONCLUSIONS: Chronic diffusion of urinary potassium into the bladder interstitium may induce sensory symptoms, damage tissue and be a major toxic factor in the pathogenesis of interstitial cystitis. Intravesical potassium sensitivity is a reliable method for detecting abnormal epithelial permeability. It discriminates between patients with interstitial cystitis and normal subjects with intact epithelial function, and it is a useful diagnostic test for interstitial cystitis. Potassium sensitivity correlates with increased potassium absorption in normal subjects, and potassium is far more provocative than sodium. Potassium sensitivity is also present in acute urinary tract infection and occasionally detrusor instability but not in BPH or chronic urinary tract infections.

Adult↗
PubMed1997

Effect of long-term oral L-arginine on the nitric oxide synthase pathway in the urine from patients with interstitial cystitis.

PURPOSE: We attempted to determine whether oral L-arginine, the substrate for nitric oxide synthase, increases nitric oxide synthase activity and cyclic guanosine monophosphate (cGMP) levels in the urine from interstitial cystitis patients. Nitric oxide and cGMP are decreased in urine from interstitial cystitis patients and both induce smooth muscle relaxation and immunological responses. Increasing urinary nitric oxide and cGMP may ameliorate interstitial cystitis symptoms. MATERIALS AND METHODS: Eight patients with interstitial cystitis were given L-arginine (1,500 mg. a day) orally for 6 months. Before and during treatment nitric oxide synthase activity and inducible nitric oxide synthase protein, cGMP, nitrate plus nitrite and interleukin 8 (IL-8) levels were measured in urine. RESULTS: After 2 weeks to 1 month of oral L-arginine treatment, urinary levels of nitric oxide synthase related enzymes and products increased significantly, while levels of the cytokine IL-8 were not changed significantly. IL-8 was significantly elevated in interstitial cystitis patients with leukocyte esterase positive urine. CONCLUSIONS: Long-term oral administration of L-arginine increases nitric oxide related enzymes and metabolites in the urine of patients with interstitial cystitis, which is associated with a decrease in interstitial cystitis related symptoms.

Administration, Oral↗