l-Arginine Administration During Reperfusion Improves Pulmonary Function

Background. Nitric oxide is crucial to the maintenance of vascular homeostasis. Because nitric oxide levels decline upon lung reperfusion, infusion of l-arginine, a nitric oxide precursor, during reperfusion might prove effective at ameliorating reperfusion injury.Methods. Neonatal piglet heart-lung blocks were preserved with Euro-Collins solution for 12 hours, rewarmed at room temperature for 1 hour, and reperfused for 10 minutes with either whole blood (n = 5), whole blood containing l-arginine (10 mmol/L; n = 6), or leukocyte-depleted blood (n = 6) on an isolated, blood-perfused, working heart-lung circuit. After the initial 10 minutes, all blocks received whole blood for 4 hours. Control blocks were continuously perfused on the circuit without intervening ischemia (n = 6).Results. The partial pressure of oxygen in the whole blood group (113.8 ± 33.1 mm Hg) was significantly less than in controls (417.3 ± 6.2 mm Hg; p < 0.01). Lung compliance was significantly less in the whole blood group (0.8 ± 0.2 mL/cm H₂O) than in controls (2.9 ± 0.4 mL/cm H₂O; p < 0.01). The l-arginine and leukocyte-depleted blood groups showed no significant difference from controls.Conclusions. l-Arginine infusion during reperfusion improves pulmonary function, making it a simple alternative to leukocyte depletion.     

Relationship among symptoms,mood, and personality traits in patients with interstitial cystitis/bladder pain syndrome

ObjectiveWe have proposed an analysis of personality traits to classify patients with interstitial cystitis/bladder pain syndrome (IC/BPS) to determine the association between symptoms, mood, and personality traits in IC/BPS patients.Materials and methodsA total of 57 patients (7 males and 50 females) diagnosed according to the National Institute of Diabetes and Digestive and Kidney Diseases criteria were recruited from December 2005 to June 2006. All of these patients were newly diagnosed cases of IC/BPS, and the evaluation was made during the admission after hydrodistension. This study used the O'Leary–Sant Symptom Index and Problem Index (interstitial cystitis system index and interstitial cystitis problem index) to record the clinical symptoms of all IC/BPS patients. Basic Personality Inventory and Back Anxiety Inventory were used to analyze personality traits and mood status.ResultsIC/BPS patients have personality traits of depression and hypochondriasis, and show moderate anxiety mood. The duration of the symptoms is longer in depressive IC/BPS patients. Significant positive correlations were found among pain and anxiety mood, symptoms and interpersonal problems, and problem index and depression, respectively. Patients with severe anxiety mood status have abnormal personality traits such as depression, anxiety, self-depreciation, and others.ConclusionsIC/BPS patients frequently exhibit several mental health disorders and negative personality traits. Therefore, in addition to targeting the bladder pathological condition, psychological intervention focusing on personality traits and anxiety mood status should be provided to improve quality of life of IC/BPS patients.     

Intravesical nitric oxide production discriminates between classic and nonulcer interstitial cystitis

PURPOSE: Interstitial cystitis (IC) is one of the most bothersome conditions in urological practice. There are 2 subtypes, classic and nonulcer IC, with similar symptoms but different outcomes with respect to clinical course and response to treatment. Histologically there are fundamental differences between the 2 subtypes, classic IC presenting a severe abnormality of the urothelium and characteristic inflammatory cell infiltrates while inflammation is scant in nonulcer IC. Regulation of urinary nitric oxide synthase activity has been proposed to be of importance for immunological responses in IC. We present evidence of a profound difference between the 2 subtypes concerning nitric oxide production, mirroring the differences in inflammatory response in IC.MATERIALS AND METHODS: A total of 17 patients with both subtypes and active disease as well as patients with disease in remission were included in the study, all diagnosed according to National Institute for Diabetes and Digestive and Kidney Diseases criteria. Luminal nitric oxide was measured in the bladder of patients using a chemiluminescence nitric oxide analyzer. RESULTS: All patients with classic IC had high levels of NO. None of the other patients had any significant increase in NO levels in the bladder. The NO level in patients with classic IC was not related to symptoms but rather to the assignment to this specific subgroup of IC. The highest levels of NO were found in patients in the initial phase of classic IC. CONCLUSIONS: The difference in NO evaporation between classic and nonulcer IC allows for subtyping of cases meeting National Institute for Diabetes and Digestive and Kidney Diseases criteria without performing cystoscopy. The findings in the present series together with previous findings clearly demonstrate that the 2 subtypes of IC represent separate entities. This separation further emphasizes the need to subtype all cases included in all scientific matters, ensuring that the 2 subtypes are evaluated separately in clinical studies.     

Dyspareunia and chronic pelvic pain in patients with interstitial cystitis/bladder pain syndrome

ObjectiveA previous study established that interstitial cystitis/bladder pain syndrome (IC/BPS) patients had significantly more dyspareunia and fear of pain than healthy controls. We evaluated the relationships between lower urinary tract symptoms and dyspareunia in IC/BPS patients.Materials and methodsA total of 156 IC/BPS female patients were included in this study. The diagnosis was made on the consensus of IC/PBS proposed by the Society for Urodynamics and Female Urology criteria in 2008. All women completed measures of pain severity (visual analog scale) and bladder symptom severity [IC Symptom Index, IC Problem Index, and the Pelvic Pain and Urinary/Frequency (PUF) scale]. Respondents were asked to recall if they experienced any sexual pain during or after sexual intercourse in the past 1 year. Cystoscopic hydrodistension during general anesthesia was performed for 5 minutes and maximal bladder capacity was also measured. Bivariate analyses were performed using chi-square and independent Student t tests.ResultsOf the women with a current sexual partner, 61% (96/156) reported dyspareunia during or after sexual intercourse. Of the 96 dyspareunia respondents, 46% (44/96) reported pain in the bladder only, 43% (41/96) in the vagina only, and 11% (11/96) in both the bladder and the vagina. Patients with dyspareunia complained of more severe urological pain (p = 0.02), a higher PUF scale score (p < 0.01), and larger anesthetic maximal bladder capacity (p = 0.04) than patients without dyspareunia. However, patients with dyspareunia at the bladder only had more severe urgency sensation (p < 0.01) but no differences in pain, PUF scale, severity of glomerulation, and maximal bladder capacity than those with dyspareunia at the vagina only.ConclusionIC/BPS women with dyspareunia have significantly more severe urological pain and a higher PUF scale score than women without dyspareunia. Physicians should consider sexual pain disorder in the management of patients with IC/BPS and use the PUF scale to evaluate not only IC-specific lower urinary tract symptoms, but also sexual pain disorder.     

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.     

Role of liposome in treatment of overactive bladder and interstitial cystitis

Intravesical (local) therapy of agents has been effective in delaying or preventing recurrence of superficial bladder cancer. This route of drug administration has also shown tremendous promise in the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS) and overactive bladder without systemic side effects. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core. They can incorporate drug molecules, both hydrophilic and hydrophobic, and show greater uptake into cells via endocytosis. Intravesical liposomes have therapeutic effects on IC/PBS patients, mainly because of their ability to form a protective lipid film on the urothelial surface. Recent studies have shown the sustained efficacy and safety of intravesical instillation of botulinum toxin formulated with liposomes (lipo-BoNT) for the treatment of refractory overactive bladder This review considers the current status of intravesical liposomes or liposomal mediated drug delivery for the treatment of IC/PBS and overactive bladder.     

Depressive symptoms and quality of life in patients with interstitial cystitis

PURPOSE: Previous research suggests that patients with interstitial cystitis have poorer quality of life and higher levels of depressive symptoms. However, most studies to date have been limited by the lack of standard measures to describe the experience of living with interstitial cystitis. In addition, to our knowledge no study has used a structured interview to assess depressive symptomatology. We investigated the extent of depressive symptoms and impaired quality of life in a sample of female patients with interstitial cystitis compared with healthy controls. Relationships among physician rated symptom severity, quality of life and depressive symptoms were also examined. MATERIALS AND METHODS: At a clinic visit 65 female patients previously diagnosed with interstitial cystitis and 40 age matched, healthy controls completed questionnaires on depressive symptoms (Beck Depression Inventory) and quality of life (Medical Outcomes Study 36-Item Short Form), and a structured interview on depressive symptoms (Hamilton Rating Scale for Depression) with trained interviewers. RESULTS: Patients reported compromised quality of life compared with healthy controls across various domains, including physical functioning, ability to function in one's normal role and vitality. They also had more severe depressive symptoms on the 2 depression measures. In patients, greater interstitial cystitis severity was associated with greater compromise in physical and social functioning, and mental health but not in other quality of life domains or depressive symptoms. CONCLUSIONS: A diagnosis of interstitial cystitis is related to poorer functioning in various life domains. Decrements increase with disease severity.     

Voiding urges perceived by patients with interstitial cystitis/painful bladder syndrome

AIMS: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a symptom-based diagnosis. We studied the IC/PBS symptom commonly referred to as "urgency" and its relationship to IC/PBS pain in a group of women with recent onset of the disease. METHODS: As part of a case control study to identify risk factors for IC, cases completed a questionnaire including two statements regarding the perceived cause of their urge to void. One was related to fear of incontinence and the other was linked with relief of pain. A Likert scale indicating level of agreement/disagreement comprised the response options. RESULTS: Most respondents (65%) agreed with the statement linking urge with pain relief. A minority (21%) concurred with the fear of incontinence statement. Disagreement for both was found in 19%. A substantial proportion (46%) agreed with pain relief but also disagreed that urge is related to fear of incontinence. Those who reported urge to relieve pain were significantly more likely to report worsened pain with bladder filling and/or improved pain with voiding. There were no such associations with urge to prevent incontinence. Overactive bladder or diabetes prior to IC onset did not confound these results. CONCLUSIONS: At least two distinct experiences of urge to urinate are evident in this population. For most, urge is linked with pain relief and is associated with bladder filling/emptying. About 1/5 reported urge to prevent incontinence. A similar portion did not agree with either urge, indicating that they may experience something altogether different, which requires further inquiry.     

Changes in urine markers and symptoms after bladder distention for interstitial cystitis

PURPOSE: We evaluated changes in urine markers and symptom scores after bladder distention in patients with interstitial cystitis. MATERIALS AND METHODS: Study subjects were 33 new patients who had undergone no prior interstitial cystitis treatment. Urine specimens were taken before and 1 month after bladder distention. University of Wisconsin symptom scores were done the same day as the urine specimen collection. Urine marker levels and symptom scores before and after distention were compared. Changes in markers were tested for associations with changes in symptom scores and other markers. Markers and specific symptoms before distention were tested for their association with post-distention symptom improvement. RESULTS: After distention the median total University of Wisconsin score decreased significantly (28.5 before, 20 after, p <0.001). A total of 12 patients (36%) had at least 30% improvement in University of Wisconsin score, and 8 patients (24%) had at least 50% improvement. No pre-distention markers or symptoms predicted which patients would have a good response. There were 2 urine markers that improved significantly after distention: anti-proliferative factor activity (median -96% before, -17% after, p <0.001) and heparin-binding epidermal growth factor-like growth factor levels (median 0.34 ng/mg creatinine before, 4.1 after, p <0.001). None of the changes in urine markers associated with changes in symptom scores. CONCLUSIONS: The median symptom score for newly diagnosed patients with interstitial cystitis decreased after distention, but only a minority of patients had at least 30% symptom improvement. Bladder distention altered urine anti-proliferative factor activity and heparin-binding epidermal growth factor-like growth factor levels toward normal, but the mechanism of symptom relief after distention is still unknown.     

Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot

Over the last 6 years there have been ongoing efforts around the world to standardize nomenclature, definition, and evaluation of interstitial cystitis/bladder pain syndrome/painful bladder syndrome. The convergence this year of several new projects stimulated an effort to bring together thought leaders from around the world to give a snapshot of current thinking with regard to this disorder. The Society for Urodynamics and Female Urology brought together thought leaders from Europe, Asia, and the United States to Miami, and a broad, structured discussion ensued which is the subject of this report. The most appropriate name of the disease remains an area of contention. A final “definition” of BPS/IC did garner substantial agreement among participants: An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable causes. It seems that the world is moving to a presumptive diagnosis based on history and physical examination, and relying on invasive procedures for more complex cases, although this is by no means a universal opinion, being more prevalent in the United States and Asia than in Europe. It is hoped that the conference proceedings can serve as a basis for future efforts to develop formal definitions, guidelines, and best practice policies to further advancement of the field. Neurourol. Urodynam. 28:274–286, 2009. © 2009 Wiley‐Liss, Inc.