Potential Urine and Serum Biomarkers in Patients with Bladder Pain Syndrome/Interstitial Cystitis.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common chronic disease, and its aetiology and pathogenesis remain unclear. This study aimed to identify potential urine and serum biomarkers in patients with IC/BPS to further understand the pathogenesis and diagnosis of the disease. METHODS: Patients with IC/BPS diagnosed and treated in the First Hospital of Hebei Medical University from 1 July 2021 to 30 July 2023 were selected. The urine and serum biomarkers of 50 patients with IC/BPS were investigated and compared with the urine and serum samples of 50 healthy controls. IBM SPSS Statistics 26.0 was used for statistical analysis of the recorded data by using chi-square test, T-test and logistic regression analysis. RESULTS: Overall, 50 patients with IC/BPS (mean age, 54.20 ± 8.15 years) were included in the study. Those with history of urinary diseases, anxiety or depression were susceptible to IC/BPS. Levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), nerve growth factor, and prostaglandin E2 (PGE2) in urine, as well as IL-8, TNF-α, and PGE2 in serum, were found to significantly increase in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). These differences were statistically significant (p < 0.05). Multifactor analysis showed that anxiety, depression, IL-6, IL-8, TNF-α and PEG2 are risk factors for patients with IC/BPS. CONCLUSIONS: Multiple biomarkers were identified in the urine and serum of patients with IC/BPS, suggesting a potential close relationship to the pathogenesis of IC/BPS.

A nomogram for bladder pain syndrome/interstitial cystitis based on netrin-1.

PURPOSE: This study aimed to combine plasma netrin-1 and clinical parameters to construct a diagnostic model for bladder pain syndrome/interstitial cystitis (BPS/IC). METHODS: We analyzed the independent diagnostic value of netrin-1 and the correlation with clinical symptom scores of BPS/IC. Clinical parameters were selected using LASSO regression, and a multivariate logistic regression model based on netrin-1 was established, and then a nomogram of BPS/IC prevalence was constructed. The nomogram was evaluated using calibration curves, the C-index, and decision curve analysis (DCA). Finally, the model was validated using an internal validation method. RESULTS: The area under the curve for the ability of netrin-1 to independently predict BPS/IC diagnosis was 0.858 (p < 0.001), with a sensitivity of 85% and specificity of 82%. The predicted nomogram included three variables: age, CD3 + /CD4 + T lymphocyte ratio, and netrin-1. The C-index of this nomogram was 0.882, and the predicted values were highly consistent with the actual results in the calibration curve. In addition, the internally validated C-index of 0.870 confirms the high reliability of the model. DCA results show that the net patient benefit of the netrin-1 combined with other clinical parameters was higher than that of the single netrin-1 model. CONCLUSION: Netrin-1 can be used as a diagnostic marker for BPS/IC and is associated with pain. The nomogram constructed by combining netrin-1 and clinical parameters was able to predict BPS/IC with great accuracy. In addition, Netrin-1 may also serve as a novel therapeutic target for BPS/IC.

Diagnostic Utility of Serum and Urinary Metabolite Analysis in Patients with Interstitial Cystitis/Painful Bladder Syndrome.

OBJECTIVE: To identify the potential biomarkers of interstitial cystitis/painful bladder syndrome (IC), a chronic syndrome of bladder-centric pain with unknown etiology that has an adverse impact on quality of life, we analyzed the urine and serum metabolomes of a cohort of IC patients and non-disease controls (NC). METHODS: Home collection of serum and urine samples was obtained from 19 IC and 20 NC females in the Veterans Affairs (VA) Health Care System. IC was diagnosed independently by thorough review of medical records using established criteria. Biostatistics and bioinformatics analyses, including univariate analysis, unsupervised clustering, random forest analysis, and metabolite set enrichment analysis (MSEA), were then utilized to identify potential IC biomarkers. RESULTS: Metabolomics profiling revealed distinct expression patterns between NC and IC. Random forest analysis of urine samples suggested discriminators specific to IC; these include phenylalanine, purine, 5-oxoproline, and 5-hydroxyindoleacetic acid. When these urinary metabolomics-based analytes were combined into a single model, the AUC was 0.92, suggesting strong potential clinical value as a diagnostic signature. Serum-based metabolomics did not provide potential IC discriminators. CONCLUSION: Analysis of serum and urine revealed that women with IC have distinct metabolomes, highlighting key metabolic pathways that may provide insight into the pathophysiology of IC. The findings from this pilot study suggest that integrated analyses of urinary metabolites, purine, phenylalanine, 5-oxoproline, and 5-HIAA, can lead to promising IC biomarkers for pathophysiology of IC. Validation of these results using a larger dataset is currently underway.

Serum sphingosine-1-phosphate levels in bladder pain syndrome/interstitial cystitis patients: could it help in diagnosis?

PURPOSE: To find if there is any potential benefit of serum Sphingosine-1-Phosphate (S1P) level in the diagnosis of Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC). METHODS AND MATERIALS: Patients newly or previously diagnosed with BPS/IC between September 2017 and December 2018 were included. Healthy individuals who volunteered to enter the study were included as control group. The measurements of serum S1P in both groups were compared. Multiple regression analysis was conducted to find out the significant factors affecting S1P results. RESULTS: A total of 47 BPS/IC patients and 47 healthy controls were included. BPS/IC patients were older than controls (48.5 ± 12.4 vs 38.9 ± 8.1 years, p < 0.001). The female-to-male ratio was 46/1 for patient group and 29/18 for controls. 68.1% (32/47) of BPS/IC patients had previous treatments. 55.3%(26/47) of patient group had accompanying medical or psychiatric disease. The mean serum S1P level was notably elevated in BPS/IC group (median 213.6, mean ± SD 258.9 ± 167.2 vs median 125.4, mean ± SD 142.9 ± 54.8; p < 0.001). Using ROC curve analysis, a value of 165 was a good cutoff point between patient and control groups (AUC = 0.761, p < 0.001). On multiple regression analysis, being BPS/IC patient was the only significant predictor of a serum S1P level above the cutoff point documented on ROC analysis (OR 5.9; 95% CI 1.8-19.9; p = 0.004). CONCLUSION: Sphingosine-1-phosphate (S1P) pathway seems to have a potential role in the pathogenesis of BPS/IC. High serum S1P level might support the diagnosis of BPS/IC.

Effect of Water Avoidance Stress on serum and urinary NGF levels in rats: diagnostic and therapeutic implications for BPS/IC patients.

Nerve growth factor (NGF) is thought to play a key role in chronic pain felt by bladder pain syndrome/interstitial cystitis (BPS/IC) patients by activating its high affinity receptor tropomyosin-related kinase subtype A (Trk A). Whether this pathway is also involved in the aggravation of pain sensation during stress events was here investigated. The levels of plasmatic NGF were increased in rats submitted to Water Avoidance Stress test (WAS), compared to controls. The administration of the alpha1A adrenoceptors blocker silodosin prevented the increase of plasmatic NGF. Urinary NGF levels were also moderately increased in animals submitted to WAS. WAS increased pain behaviour score, lowered abdominal mechanical pain threshold and increase voiding bladder reflex activity. These changes were prevented by the administration of TrkA antagonist GW441756. These findings prompt the use of plasmatic NGF as diagnosis tool for chronic visceral painful conditions and opens therapeutic opportunities for TrkA receptors antagonist/NGF sequestration.

Elevated Urine Levels of Macrophage Migration Inhibitory Factor in Inflammatory Bladder Conditions: A Potential Biomarker for a Subgroup of Interstitial Cystitis/Bladder Pain Syndrome Patients.

OBJECTIVE: To investigate whether urinary levels of macrophage migration inhibitory factor (MIF) are elevated in interstitial cystitis/bladder pain syndrome (IC/BPS) patients with Hunner lesions and also whether urine MIF is elevated in other forms of inflammatory cystitis. METHODS: Urine samples were assayed for MIF by enzyme-linked immunosorbent assay. Urine samples from 3 female groups were examined: IC/BPS patients without (N = 55) and with Hunner lesions (N = 43), and non-IC/BPS patients (N = 100; control group; no history of IC/BPS; cancer or recent bacterial cystitis). Urine samples from 3 male groups were examined: patients with bacterial cystitis (N = 50), radiation cystitis (N = 18) and noncystitis patients (N = 119; control group; negative for bacterial cystitis). RESULTS: Urine MIF (mean MIF pg/mL ± standard error of the mean) was increased in female IC/BPS patients with Hunner lesions (2159 ± 435.3) compared with IC/BPS patients without Hunner lesions (460 ± 114.5) or non-IC/BPS patients (414 ± 47.6). Receiver operating curve analyses showed that urine MIF levels discriminated between the 2 IC groups (area under the curve = 72%; confidence interval 61%-82%). Male patients with bacterial and radiation cystitis had elevated urine MIF levels (2839 ± 757.1 and 4404 ± 1548.1, respectively) compared with noncystitis patients (681 ± 75.2). CONCLUSION: Urine MIF is elevated in IC/BPS patients with Hunner lesions and also in patients with other bladder inflammatory and painful conditions. MIF may also serve as a noninvasive biomarker to select IC/BPS patients more accurately for endoscopic evaluation and possible anti-inflammatory treatment.

Urinary Microbiome and Cytokine Levels in Women With Interstitial Cystitis.

OBJECTIVE: To investigate differences in the urinary microbiome and cytokine levels between women with and without interstitial cystitis and to correlate differences with scores on standardized symptom severity scales and depression and anxiety screening tools. METHODS: Our cross-sectional study compared women presenting to a pelvic floor clinic and diagnosed with interstitial cystitis over a 6-month period with age-matched women in a control group from the same institution. Participants provided a catheterized urine sample and completed symptom severity, quality-of-life, depression, and anxiety screening questionnaires. Urinary microbiomes generated through bacterial ribosomal RNA sequencing and cytokine levels were analyzed using a standard immunoassay. Nonparametric analyses were used for all comparisons. RESULTS: Participants with interstitial cystitis reported more disability, bothersome urinary symptoms, genitourinary pain, and sexual dysfunction and scored higher on depression and anxiety screens compared with women in the control group. The urine of participants with interstitial cystitis contained fewer distinct operational taxonomic units (2 [median range 2-7, interquartile range 1] compared with 3.5 [median, range 2-22, interquartile range 5.25], P=.015) and was less likely to contain Lactobacillus acidophilus (1/14 [7%] compared with 7/18 [39%], P=.05) compared with women in the control group. L acidophilus was associated with less severe scores on the Interstitial Cystitis Symptoms Index (1 [median, range 0-17, interquartile range 5] compared with 10 [median, range 0-14, interquartile range 11], P=.005) and the Genitourinary Pain Index (0 [median, range 0-42, interquartile range 22] compared with 22.5 [median, range 0-40, interquartile range 28], P=.03). Participants with interstitial cystitis demonstrated higher levels of macrophage-derived chemokine (13.32 [median, range 8.93-17.05, interquartile range 15.86] compared with 0 [median, range 8.93-22.67, interquartile range 10.35], P=.037) and interleukin-4 (1.95 [median, range 1.31-997, interquartile range 11.84] compared with 1.17 [median, range 0.44-3.26, interquartile range 1.51], P=.029). There was a positive correlation between interleukin-4 and more severe scores on the Interstitial Cystitis Symptoms Index (r=0.406, P=.013). No associations between the presence of lactobacillus species and cytokine levels were observed. CONCLUSION: The urinary microbiome of participants with interstitial cystitis was less diverse, less likely to contain Lactobacillus species, and associated with higher levels of proinflammatory cytokines. It is unknown whether this represents causality and whether the effect of alterations to the urinary microbiome is mediated through an inflammatory response.

Elevated serum IgE may be associated with development of ketamine cystitis.

PURPOSE: Previous studies revealed bladder mast cell and eosinophil cell infiltration in patients with ketamine cystitis. Due to possible hypersensitivity in those with this condition we investigated the association of serum Ig, histology findings and symptoms in patients with ketamine cystitis. MATERIALS AND METHODS: We evaluated patients with ketamine cystitis for maximal bladder capacity, serum IgE, IgG and IgM, and pain visual analog scale score. Bladder biopsies were assessed for mast cells and eosinophils. Patients with interstitial cystitis/bladder pain syndrome, acute bacterial cystitis and controls were also studied. We used the Mann-Whitney U test for nonparametric data to compare serum IgE among groups with p <0.017 considered significant. RESULTS: Median serum IgE was significantly higher in the 20 patients with ketamine cystitis (205.5 IU/ml, IQR 36.9, 514.0) than in the 10 controls (33.4 IU/ml, IQR 13.5, 71.7, p = 0.015) and the 15 with acute bacterial cystitis (34.6 IU/ml, IQR 24.2, 101.9, p = 0.015). It was marginally higher than in the 13 patients with interstitial cystitis/bladder pain syndrome (65.8 IU/ml, IQR 11.9, 133.0, p = 0.029). Of patients with ketamine cystitis the median visual analog scale pain score was significantly higher in those with serum IgE greater than compared to less than 200 IU/ml. Maximal bladder capacity was significantly less in patients with ketamine cystitis who had higher IgE. Patients with severe or moderate bladder eosinophil infiltration had a greater visual analog scale score, higher serum IgE and smaller maximal bladder capacity than patients with no or mild eosinophil infiltration. Serum IgE and the visual analog scale score correlated significantly (r(2) = 0.318, p = 0.01). CONCLUSIONS: Patients with ketamine cystitis had higher serum IgE than patients with interstitial cystitis/bladder pain syndrome or acute bacterial cystitis, or controls. Serum IgE and the severity of eosinophil infiltration were associated with bladder pain severity and small maximal bladder capacity.

What is the role for biomarkers for lower urinary tract disorders? ICI-RS 2013.

AIMS: A biomarker is an entity that measures a normal or pathological process, or the response to an intervention. A biomarker must measure exclusively and be sufficiently sensitive to the process of interest. Alternatively, a biomarker may give clues regarding the underlying pathology of the condition and be a useful research or specialist tool. If a biomarker is to be of practical benefit then it must also be economical and practical to use. This article will consider chemical moieties as biomarkers, although in principle physical markers (e.g., bladder wall thickness) could also be defined as such. RESULTS AND CONCLUSIONS: The validation of a biomarker for detrusor overactivity (DO) must appreciate the fact that the condition is likely to multifactorial and thus no single entity may be sufficiently selective and sensitive. However, more specific conditions, such as bladder pain associated with DO, may make the biomarker search easier. Several prospective agents including antiproliferative factor (APF) and epidermal growth factors (EGF) are discussed. Several urinary biomarkers, including neurotrophins (NGF, BDNF) and cytokines, and a serum marker, C-reactive protein, are considered as reaching the above criteria. All suffer from relatively poor lack of discrimination, as they all change in response to other, often inflammatory, conditions; BDNF may offer the highest expectations. Urinary ATP has also been proposed as a DO/OAB biomarker but requires further evaluation. Finally genetic markers offer potential to understand more about the pathophysiology of DO/OAB. The increasing availability of genome-wide association studies and micro-RNA assays offer genetic markers as a new generation of biomarkers. Neurourol. Urodynam. 33:602-605, 2014. © 2014 Wiley Periodicals, Inc.

Increased pro-inflammatory cytokines, C-reactive protein and nerve growth factor expressions in serum of patients with interstitial cystitis/bladder pain syndrome.

OBJECTIVE: The etiology and pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) are unclear. Chronic inflammation is considered the main pathology of IC/BPS. This study measured the serum c-reactive protein (CRP), nerve growth factor (NGF) and pro-inflammatory cytokine/chemokine interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and IL-8 expression in patients with IC/BPS to elucidate the involvement of systemic inflammation in IC/BPS. METHODS: Serum samples were collected from 30 IC/BPS patients and 26 control subjects. The concentrations of serum nerve growth factor (NGF), IL-1ß, IL-6, TNF-α, and IL-8 were quantified using a bead-based, human serum adipokine panel kit. Serum C-reactive protein (CRP) was also assessed. Differences of serum CRP, NGF, IL-1ß, IL-6, TNF-α, and IL-8 levels between the IC/BPS patients and controls were compared, and correlations between CRP and pro-inflammatory cytokines and chemokine were also evaluated. RESULTS: The results showed that CRP level (p = 0.031), NGF (p = 0.015) and pro-inflammatory cytokines/chemokine IL-1ß, IL-6, TNF-α, and IL-8 levels were significantly higher in the patients with IC/BPS than among controls (all p<0.001). Significant associations were observed between IL-1ß and IL-8 (p<0.001), IL-6 and CRP (p = 0.01), IL-6 and IL-8 (p = 0.02), and IL-6 and TNF-α (p = 0.03). CONCLUSION: Increased pro-inflammatory cytokines/chemokine (IL-1ß, IL-6, TNF-α, and IL-8) expression in the sera of IC/BPS patients implies not only mast cell activation, but also that other inflammatory mediators play important roles in the pathogenesis of IC/BPS. Thus, for some patients, IC/BPS is considered a chronic inflammatory disease.

Highlights in basic autonomic neuroscience: contribution of the urothelium to sensory mechanisms in the urinary bladder.

Urothelial cells in the urinary bladder express neural properties including: (1) release of neurotransmitters and neurotrophic factors, (2) expression of neurotransmitter receptors and ion channels, and (3) sensitivity to mechanical and chemical stimuli. These properties have focused attention on the possible contribution of the urothelium to the storage and emptying functions of the bladder. In addition chemicals released from urothelial cells can affect the excitability of adjacent afferent nerves and this interaction can be affected by pathological conditions. This raises the possibility that abnormal urothelial-afferent interactions may contribute to bladder dysfunctions and therefore be a target for drug therapy.

Increased urine and serum nerve growth factor levels in interstitial cystitis suggest chronic inflammation is involved in the pathogenesis of disease.

OBJECTIVE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is considered a bladder disorder due to localized chronic inflammation. This study investigated the nerve growth factor (NGF) levels in serum and urine in patients with IC/BPS. MATERIALS AND METHODS: Thirty patients with IC/BPS and 28 normal subjects without lower urinary tract symptoms were recruited from an outpatient clinic. IC/BPS was diagnosed by frequency, bladder pain, and the presence of glomerulations during cystoscopic hydrodistention. Serum and urine were collected before any treatment was given. Serum NGF and urinary NGF/Cr levels were compared between IC/BPS and the controls. RESULTS: Urinary NGF levels were significantly higher in patients with IC/PBS (26.3±11.2 pg/ml) than in controls (1.40±0.63 pg) (p = 0.014). After normalization, the urinary NGF/Cr levels were significantly greater in IC/BPS (0.69±0.38 pg/mg) than controls (0.20±0.01, p = 0.011). Relative to the levels in control subjects (1.90±0.38 pg/mL), the mean serum NGF levels were higher in patients IC/BPS patients (3.48±0.55 pg/mL) (p = 0.015). No significant correlation was found between the serum and urinary NGF levels in IC/BPS patients. However, the clinical characteristics and medical co-morbidities did not show significant difference between IC/BPS patients with a higher and lower serum NGF level. CONCLUSIONS: Increased urinary NGF levels in IC/BPS patients suggest that chronic inflammation is involved in this bladder disorder. Increased circulating serum NGF levels were noted in over half of patients with IC/BPS, however, the urinary and serum NGF were not inter-correlated and elevated serum NGF did not relate with clinical features.

Elevation of serum c-reactive protein in patients with OAB and IC/BPS implies chronic inflammation in the urinary bladder.

AIMS: Chronic inflammation has been implicated in the development of overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). An elevation of C-reactive protein (CRP) has been associated with chronic inflammation and lower urinary tract symptoms. This study aims to elucidate the association between CRP and OAB or IC/BPS. METHODS: Serum CRP and urinary nerve growth factor (NGF) levels were examined in 70 patients with OAB (n=22) or IC/BPS (n=48) and compared with 33 normal controls. Data of serum CRP and urinary NGF levels were compared among the controls, IC/PBS, and OAB. The Spearmen correlation analysis test and ANOVA (Kruskal-Wallis) test were used for statistical analysis with P<0.05 considered significant. RESULTS: Serum CRP levels were significantly higher in subjects with OAB (1.83 ± 2.30 mg/L vs. 0.59 ± 0.40 mg/L, P=0.012) or IC/BPS (1.76 ± 3.56 mg/L vs. 0.59 ± 0.40 mg/L, P=0.049) than in controls. No significant difference in CRP level was noted between patients with OAB and IC/BPS (P=0.43). In a subgroup analysis, patients of OAB wet had higher serum CRP level than that of OAB dry (2.95 ± 3.08 mg/L vs. 0.90 ± 0.52 mg/L); however, the difference did not reach statistical significance (P=0.34). The CRP between OAB wet and OAB patients with medical disease was not significantly different. There was no significant correlation between serum CRP and urinary NGF levels in the controls or patients with OAB or IC/BPS, except in the OAB patients with a CRP level >3 mg/L. CONCLUSIONS: Our data support the association between chronic inflammation of the urinary bladder in patients with OAB or IC/BPS.

A candidate serum biomarker for bladder pain syndrome/interstitial cystitis.

Reliable diagnostic markers for Bladder Pain Syndrome/Interstitial Cystitis (IC) currently are not available. This study evaluated the feasibility of diagnosing IC in humans and domestic cats from the spectra of dried serum films (DSFs) using infrared microspectroscopy. Spectra were obtained from films from 29 humans and 34 domestic cats to create classification models using Soft Independent Modeling by Class Analogy (SIMCA). Ultrafiltration of serum improved discrimination capability. The classification models for both species successfully classified spectra based on condition (healthy/sick), and a different set of masked spectra correctly predicted the condition of 100% of the subjects. Classification required information from the 1500-1800 cm(-1) spectral region to discriminate between subjects with IC, other disorders, and healthy subjects. Analysis of cat samples using liquid chromatography-mass spectroscopy revealed differences in the concentration of tryptophan and its metabolites between healthy and affected cats. These results demonstrate the potential utility of infrared microspectroscopy to diagnose IC in both humans and cats.

Urinary and Serologic Markers forInterstitial Cystitis: An Update.

This update reviews the published literature from the past 2 years pertaining to urinary and serum markers for interstitial cystitis (IC). Literature on markers described before 2004 also is included when needed to provide background information for the current literature. The markers that have been the focus of the most research in the recent literature are antiproliferative factor, epidermal growth factor, heparin-binding epidermal growth factor-like growth factor, glycosaminoglycans, and bladder nitric oxide. These markers are discussed in consideration of their three different possible roles: 1) as diagnostic markers of IC; 2) distinguishing relevant subsets of IC patients; and 3) measuring disease activity and objectively following treatment response.

Diurnal cortisol variations and symptoms in patients with interstitial cystitis.

PURPOSE: Little attention has focused on systemic factors that may allow a state of chronic bladder inflammation to be established and maintained in interstitial cystitis cases. Abnormalities of the hypothalamic-pituitary-adrenal feedback system result in poorer regulation of the inflammatory response and are present in many chronic inflammatory and pain conditions, of which some have high co-morbidity with interstitial cystitis. MATERIALS AND METHODS: A total of 48 patients with interstitial cystitis and 35 healthy, age matched controls collected 24-hour urine samples and 3 days of salivary samples at 7 to 8 a.m., 4 to 5 p.m. and 8 to 9 p.m. for cortisol analysis. In addition, they completed a concurrent symptom questionnaire. Prospective symptom diaries also were completed in the month before sampling. RESULTS: Mean urinary or salivary cortisol did not differ in patients and controls. However, patients with interstitial cystitis and higher morning cortisol had significantly less pain and urgency, while those with higher urinary free cortisol reported less overall symptomatology (p <0.05). Relationships with morning cortisol were also observed when controlling for co-morbid conditions known to be affected by the hypothalamic-pituitary-adrenal axis, such as fibromyalgia, chronic fatigue and rheumatoid arthritis. Patients with morning cortisol less than 12.5 nmol./l. were 12.8 times more likely to report high urinary urgency than those with values above this cutoff. CONCLUSIONS: These findings imply that regulation of the hypothalamic-pituitary-adrenal axis may be associated with interstitial cystitis symptomatology and there may be different diurnal hypothalamic-pituitary-adrenal patterns in patients with interstitial cystitis who do and do not have co-morbid conditions. These findings may have treatment implications for patients with interstitial cystitis who have early morning cortisol deficiencies.

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.

Sulfhemoglobinemia after dermal application of DMSO.

A 43-y-old Caucasian female applied 4 ounces of dimethyl sulfoxide (DMSO) to her lower abdomen for treatment of interstitial cystitis. Within 24 h she developed fatigue, cyanosis and dyspnea with mild exertion. She sought medical attention 10 d later, at which time initial laboratory tests revealed a methemoglobin level of 47%. Two doses of 1 mg methylene blue/kg i.v. were given without significant improvement in either her cyanosis or methemoglobin level. Repeat analysis the day following admission using an outside lab demonstrated a sulfhemoglobin level of 6.2% and a methemoglobin level of < 0.1%. No prior reports have associated sulfhemoglobin formation with DMSO application. Carbon monoxide-oximetry may falsely identify sulfhemoglobin as methemoglobin; sulfhemoglobinemia should be considered in cases of methemoglobinemia refractory to methylene blue therapy.