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Interstitial cystitis/painful bladder syndrome

 
Medical Dictionary: interstitial cystitis
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n.

A chronic inflammatory condition of unknown cause involving the mucosa and muscular tissue of the bladder and resulting in reduced bladder capacity.

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Interstitial cystitis/painful bladder syndrome
Classification and external resources
ICD-10 N30.1
ICD-9 595.1
DiseasesDB 30832
MedlinePlus 000477
eMedicine med/2866
MeSH D018856

Interstitial cystitis/painful bladder syndrome (commonly abbreviated to "IC/PBS"), is a urinary bladder disease of unknown cause characterised by pain associated with urination (dysuria), urinary frequency (as often as every 10 minutes), urgency, and pressure in the bladder and/or pelvis.[1] Pain that worsened with a certain food or drink and/or worsened with bladder filling and/or improved with urination was reported by 97% of patients.[2] Patients may also experience nocturia, pelvic floor dysfunction and tension (thus making it difficult to start their urine stream), pain with sexual intercourse, and discomfort and difficulty driving, traveling or working. Research has claimed that the quality of life of some IC patients is equivalent to those with end stage renal failure.[3]

It is not unusual for patients to have been misdiagnosed with a variety of other conditions, including: overactive bladder, urethritis, urethral syndrome, trigonitis, prostatitis and other generic terms used to describe frequency/urgency symptoms in the urinary tract.

IC/PBS affects men and women of all cultures, socioeconomic backgrounds, and ages. Although the disease previously was believed to be a condition of menopausal women, growing numbers of men and women are being diagnosed in their twenties and younger. IC/PBS is not a rare condition, however IC/PBS is more common in females than in men.[1] Early research suggested that IC/PBS prevalence ranged from 1 in 100,000 to 5.1 in 1,000 of the general population. Up to 12% of women may have early symptoms of IC/PBS.[4]

Contents

Nomenclature

Originally called interstitial cystitis, the name for this disorder changed to interstitial cystitis/painful bladder syndrome in the period 2002-2005. In 2007, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) began using the umbrella term Urologic Chronic Pelvic Pain Syndromes (UCPPS) to refer to pain syndromes associated with the bladder (i.e. interstitial cystitis/painful bladder syndrome, IC/PBS) and the prostate gland (i.e. chronic prostatitis/chronic pelvic pain syndrome, CP/CPPS).[5]

In 2008, terms currently in use in addition to IC/PBS include painful bladder syndrome, bladder pain syndrome and hypersensitive bladder syndrome, alone and in a variety of combinations. These different terms are being used in different parts of the world.

The term "interstitial cystitis" is the primary term used in ICD-10 and MeSH.

Causes

The cause of IC/PBS is unknown, though several theories have been put forward (these include autoimmune, neurologic, allergic and genetic).[6] Regardless of the origin, it is clear that the majority of IC/PBS patients struggle with a damaged urothelium, or bladder lining.[citation needed] When the surface glycosaminoglycan (GAG) layer is damaged (via a urinary tract infection (UTI), excessive consumption of coffee or sodas, traumatic injury, etc.), urinary chemicals can "leak" into surrounding tissues, causing pain, inflammation, and urinary symptoms. Oral medications like Elmiron and medications that are placed directly into the bladder via a catheter work to repair and rebuild this damaged/wounded lining, allowing for a reduction in symptoms.

Recent work at the University of Maryland, Baltimore indicates that genetics may be a factor in a small subset of patients. Two genes, FZD8[7] and PAND[8], are associated with the syndrome.

  • FZD8, at gene map locus 10p11.2, is associated with an antiproliferative factor secreted by the bladders of IC/PBS patients which "profoundly inhibits bladder cell proliferation," thus causing the missing bladder lining.[9]
  • PAND, at gene map locus 13q22-q32, is associated with a constellation of disorders (a "pleiotropic syndrome") including IC/PBS and other bladder and kidney problems, thyroid diseases, serious headaches/migraines, panic disorder, and mitral valve prolapse.

Symptoms

The symptoms of IC/PBS are often misdiagnosed as a "common" bladder infection (cystitis) or a UTI. However IC/PBS has not been shown to be caused by a bacterial infection, and the mis-prescribed treatment of antibiotics is ineffective. The symptoms of IC/PBS may also initially be attributed to prostatitis and epididymitis (in men) and endometriosis and uterine fibroids (in women).

The most common symptom of IC/PBS is pain, which is found in 100% of patients, frequency (82% of patients) and nocturia (62%).[10]

In general, symptoms are:

  • Pain that is worsened with bladder filling and/or improved with urination.[2]
  • Pain that is worsened with a certain food or drink.
  • Urinary frequency (as often as every 10 minutes), urgency, and pressure in the bladder and/or pelvis.
  • Some patients report dysuria (burning sensation in the urethra when urinating).
  • Some patients report waking at night to urinate, hesitancy (needing to wait for the stream to begin), pain with sexual intercourse, and discomfort and difficulty driving, travelling or working.

During cystoscopy, 5 to 10% of patients are found to have Hunner's ulcers.[6] Far more patients may experience a very mild form of IC/PBS, in which they have no visible wounds in their bladder, yet struggle with symptoms of pain, frequency and/or urgency. Still other patients may have discomfort only in their urethra, while others struggle with pain in the entire pelvis.

Diagnosis

Diagnosis has been greatly simplified in recent years with the development of two new methodologies. The Pelvic Pain Urgency/Frequency (PUF) Patient Survey, created by C. Lowell Parsons, is a short questionnaire that will help doctors identify if pelvic pain could be coming from the bladder.[11] The KCl test, also known as the potassium sensitivity test, uses a mild potassium solution to test the integrity of the bladder wall.[11] Though the latter is not specific for IC/PBS, it has been determined to be helpful in predicting the use of compounds, such as pentosan polysulphate, which are designed to help repair the GAG layer. The previous gold standard test for IC/PBS was the use of hydrodistention with cystoscopy. Researchers, however, determined that this visual examination of the bladder wall after stretching the bladder was not specific for IC/PBS and that the test, itself, can contribute to the development of small glomerulations (that is, petechial hemorrhages) often found in IC/PBS. Thus, a diagnosis of IC/PBS is one of exclusion, as well as a review of clinical symptoms.

In 2006, the ESSIC society proposed more rigorous and demanding diagnostic methods with specific classification criteria so that it cannot be confused with other, similar conditions. Specifically, they require that a patient must have pain associated with the bladder, accompanied by one other urinary symptom. Thus, a patient with just frequency or urgency would be excluded from a diagnosis. Secondly, they strongly encourage the exclusion of confusable diseases through an extensive and expensive series of tests including (A) a medical history and physical exam, (B) a dipstick urinalysis, various urine cultures, and a serum PSA in men over 40, (C) flowmetry and post-void residual urine volume by ultrasound scanning and (D) cystoscopy. A diagnosis of IC/PBS would be confirmed with a hydrodistention during cystoscopy with biopsy.

They also propose a ranking system based upon the physical findings in the bladder. Patients would receive a numeric and letter based score based upon the severity of their disease as found during the hydrodistention. A score of 1-3 would relate to the severity of the disease and a rating of A-C represents biopsy findings. Thus, a patient with 1A would have very mild symptoms and disease while a patient with 3C would have the worst available symptoms.[12]

In 2009, Japanese researchers identified a urinary marker called phenylacetylglutamine that could be used for early diagnosis.[13]

Treatment

Pelvic floor treatments

Work by Wise and Anderson (see details) has shown that urologic pelvic pain syndromes, such as IC/PBS and CP/CPPS, may have no initial trigger other than anxiety, often with an element of Obsessive Compulsive Disorder or other anxiety-spectrum problem.[14] This is theorized to leave the pelvic area in a sensitized condition resulting in a loop of muscle tension and heightened neurological feedback (neural wind-up). This is a form of myofascial pain syndrome. Current protocols largely focus on stretches to release overtensed muscles in the pelvic or anal area (commonly referred to as trigger points), physical therapy to the area, and progressive relaxation therapy to reduce causative stress.[15][16]

Most major IC/PBS clinics now evaluate the pelvic floor and/or refer patients directly to a physical therapist for a prompt treatment of pelvic floor muscle tension or weakness. Chronic pelvic floor tension can cause pain in the bladder and/or pelvis, which is often described by women as a burning sensation, particularly in the vagina. Men with pelvic floor tension experience referred pain, particularly at the tip of their penis. In 9 out 10 IC/PBS patients struggling with painful sexual relations, muscle tension is the primary cause of that pain and discomfort. Tender trigger points —small, tight, hyperirritable bundles of muscle— may also be found in the pelvic floor.[17]

Pelvic floor dysfunction is a fairly new area of specialty for physical therapists world wide. The goal of therapy is to relax and lengthen the pelvic floor muscles, rather than to tighten and/or strengthen them as is the goal of therapy for patients with incontinence. Thus, traditional exercises such as Kegels, can be helpful as they strengthen the muscles, however they can provoke pain and additional muscle tension. A specially trained physical therapist can provide direct, hands on, evaluation of the muscles, both externally and internally. While weekly therapy is certainly valuable, most providers also suggest an aggressive self-care regimen at home to help combat muscle tension, such as daily muscle relaxation audiotapes, stress reduction and anxiety management on a daily basis. Anxiety is often found in patients with painful conditions and can subconsciously trigger muscle tension.

Thiele massage

Transvaginal manual therapy of the pelvic floor musculature (Thiele massage) has shown promise in relieving the pain associated with Interstitial cystitis in at least one open, clinical pilot study.[18]

Medication

As recently as a decade ago, treatments available were limited to the use of astringent instillations, such as chlorpactin (oxychlorosene) or silver nitrate, designed to kill "infection" and/or strip off the bladder lining. In 2005, our understanding of IC/PBS has improved dramatically and these therapies are now no longer done. Rather, IC/PBS therapy is typically multi-modal, including the use of a bladder coating, an antihistamine to help control mast cell activity and a low dose antidepressant to fight neurogenic inflammation.[1]

Pentosan polysulfate

Oral pentosan polysulfate (Elmiron) is believed to provide a protective coating in the bladder, but studies show it is not statistically significant compared to placebo.[19][20] However, some studies have found that a minority of patients do respond to pentosan polysulfate.[21][22]

Amitriptyline

Amitriptyline can reduce symptoms in patients with IC/PBS.[23] Patient overall satisfaction with the therapeutic result of amitriptyline was excellent or good in 46%.[24]

Bladder instillations

DMSO, a wood pulp extract, is the only approved bladder instillation for IC/PBS yet it is much less frequently used in urology clinics. Research studies presented at recent conferences of the American Urological Association by C. Subah Packer have demonstrated that the FDA approved dosage of a 50% solution of DMSO had the potential of creating irreversible muscle contraction. However, a lesser solution of 25% was found to be reversible. Long term use is questionable, at best, particularly given the fact that the method of action of DMSO is not fully understood.[25]

Rescue instillations

More recently, the use of a "rescue instillation" composed of Elmiron or heparin, Cystistat, lidocaine and sodium bicarbonate, has generated considerable excitement in the IC/PBS community because it is the first therapeutic intervention that can be used to reduce a flare of symptoms. Published studies report a 90% effectiveness in reducing symptoms.[26]

Bladder coatings

Other bladder coating therapies include Cystistat (sodium hyaluronate) and Uracyst (chondroitin). They are believed to replace the deficient GAG layer on the bladder wall. Like most other intravesical bladder treatments, this treatment may require the patient to lie for 20 – 40 minutes, turning over every ten minutes, to allow the chemical to 'soak in' and give a good coating, before it is passed out with the urine.

Diet

The foundation of therapy is a modification of diet to help patients avoid those foods which can further irritate the damaged bladder wall. Common offenders are highly spiced or acidic foods and include alcohol, coffees, teas, herbal teas, green teas, all sodas (particularly diet), concentrated fruit juices, tomatoes, citrus fruit, cranberries, the B vitamins, vitamin C, monosodium glutamate, chocolate, and potassium-rich foods such as bananas. Most IC/PBS support groups and many urology clinics have diet lists available.

The problem with diet triggers is that they vary from person to person: the best way for a person to discover his or her own triggers is to use an elimination diet.

Anecdotal evidence has linked gluten intolerance to UCPPS symptoms.[27] Studies are lacking in this area.

Bladder distension

Bladder distension (a procedure which stretches the bladder capacity, done under general anaesthesia) has shown some success in reducing urinary frequency and giving pain relief to patients.[28] However, many experts still cannot understand precisely how this can cause pain relief.[29] Recent studies showing that pressure on pelvic trigger points can relieve symptoms may be connected. Unfortunately, the relief achieved by bladder distensions is only temporary (weeks or months) and consequently, it is not really viable as a long-term treatment for IC/PBS.

Surgery

Surgical interventions are rarely used for IC/PBS.

Pain control

Pain control is usually necessary in the IC/PBS treatment plan. The pain of IC/PBS has been rated equivalent to cancer pain and may lead to central sensitization if untreated.

Medication

The use of a variety of traditional pain medications, including opiates and synthetic opioids like tramadol, is often necessary to treat the varying degrees of pain. Even children with IC/PBS should be appropriately addressed regarding pelvic pain, and receive necessary treatment to manage it.[1]

Neuromodulation

Neuromodulation can be successful in treating IC/PBS symptoms, including pain.[30] Electronic pain-killing options include TENS.[31] PTNS stimulators have also been used, with varying degrees of success.[32] Percutaneous sacral nerve root stimulation (PNS) was able to produce statistically significant improvements in several parameters, including pain.[33]

Acupuncture

A 2002 review study reported that acupuncture alleviates pain associated with IC/PBS as part of multimodal treatment.[34] While a 1987 study showed that 11 of 14 (78%) patients had a >50% reduction in pain,[35] another study (published in 1993) found no beneficial effect.[36] A 2008 review found that although there are hardly any controlled studies on alternative medicine and IC/PBS, "rather good results have been obtained" when acupuncture is combined with other treatments.[37]

Biofeedback

Biofeedback, a relaxation technique aimed at helping people control functions of the autonomous nervous system, has shown some benefit in controlling pain associated with IC/PBS as part of a multimodal approach that may also include medication or hydrodistention of the bladder.[38][39]

Links to other conditions

It is important to note that some people with IC/PBS suffer from anxiety disorder, and other conditions that may have the same etiology as IC/PBS. These include: irritable bowel syndrome (IBS), fibromyalgia, chronic fatigue syndrome, endometriosis, vulvodynia, and chemical sensitivities. Men with IC/PBS are frequently diagnosed as having chronic nonbacterial prostatitis, and there is an extensive overlap of symptoms and treatment between the two conditions, leading researchers to posit that the conditions share the same etiology and pathology.[40]

See also

References

  1. ^ a b c d The Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies ISBN 1-57224-210-8
  2. ^ a b Warren JW, Brown J, Tracy JK, Langenberg P, Wesselmann U, Greenberg P (March 2008). "Evidence-based criteria for pain of interstitial cystitis/painful bladder syndrome in women". Urology 71 (3): 444–8. doi:10.1016/j.urology.2007.10.062. PMID 18342184. 
  3. ^ Ho N, Koziol J, Parsons CL. Epidemiology of Interstitial Cystitis, in G. Sant (Ed.), Interstitial Cystitis. Philadelphia: Lippincott-Raven Publishers, 1997; 9-15.
  4. ^ Rosenberg, Mt; Newman, Dk; Page, Sa (May 2007). "Interstitial cystitis/painful bladder syndrome: symptom recognition is key to early identification, treatment" (Free full text). Cleveland Clinic journal of medicine 74 Suppl 3: S54–62. doi:10.3949/ccjm.74.Suppl_3.S54. ISSN 0891-1150. PMID 17546832. http://www.ccjm.org/cgi/pmidlookup?view=long&pmid=17546832.  edit
  5. ^ "Multi-disciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network". NIDDK. 2007. http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-07-003.html. Retrieved 2008-01-11. 
  6. ^ a b NIDDK Interstitial Cystitis Summary - IC section of the NKUDIC
  7. ^ Online 'Mendelian Inheritance in Man' (OMIM) FRIZZLED, DROSOPHILA, HOMOLOG OF, 8; FZD8 -606146
  8. ^ Online 'Mendelian Inheritance in Man' (OMIM) PANIC DISORDER 1; PAND -167870
  9. ^ Numerous publications by Keay & colleagues available at PubMed Keay S, Zhang CO, Chai T, et al. (January 2004). "Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor in men with interstitial cystitis versus chronic pelvic pain syndrome". Urology 63 (1): 22–6. doi:10.1016/j.urology.2003.08.024. PMID 14751340. http://linkinghub.elsevier.com/retrieve/pii/S0090429503009130. 
  10. ^ Mouracade P, Lang H, Jacqmin D, Saussine C (November 2008). "[Using the intersitital cystitis new diagnostic criteria in daily practice: about 156 patients]" (in French). Prog. Urol. 18 (10): 674–7. doi:10.1016/j.purol.2008.05.001. PMID 18971112. 
  11. ^ a b Dr. Lowell Parsons website - includes references, protocols and publications.
  12. ^ ESSIC Society website - includes white papers, conference notes and protocols
  13. ^ Fukui, Y.; Kato, M.; Inoue, Y.; Matsubara, A.; Itoh, K. (November 2009). "A metabonomic approach identifies human urinary phenylacetylglutamine as a novel marker of interstitial cystitis.". J Chromatogr B Analyt Technol Biomed Life Sci 877 (30): 3806–12. doi:10.1016/j.jchromb.2009.09.025. PMID 19815468. 
  14. ^ "The Stanford Protocol". 2005. http://www.chronicprostatitis.com/spasmtx.html. Retrieved 2006-12-09. 
  15. ^ Anderson RU, Wise D, Sawyer T, Chan C (2005). "Integration of myofascial trigger point release and paradoxical relaxation training treatment of chronic pelvic pain in men". J. Urol. 174 (1): 155–60. doi:10.1097/01.ju.0000161609.31185.d5. PMID 15947608. 
  16. ^ Anderson RU, Wise D, Sawyer T, Chan CA (2006). "Sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome: improvement after trigger point release and paradoxical relaxation training". J. Urol. 176 (4 Pt 1): 1534–8; discussion 1538–9. doi:10.1016/j.juro.2006.06.010. PMID 16952676. 
  17. ^ 13. Sandler, G. Pelvic Floor Dysfunction and Problem Trigger Points in Other Areas of the Body. June 2002 IC/PBS Network Feature Column
  18. ^ Oyama IA, Rejba A, Lukban JC, et al. (November 2004). "Modified Thiele massage as therapeutic intervention for female patients with interstitial cystitis and high-tone pelvic floor dysfunction". Urology 64 (5): 862–5. doi:10.1016/j.urology.2004.06.065. PMID 15533464. 
  19. ^ Nordling J (November 2004). "Interstitial cystitis: how should we diagnose it and treat it in 2004?". Curr Opin Urol 14 (6): 323–7. doi:10.1097/00042307-200411000-00005. PMID 15626873. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0963-0643&volume=14&issue=6&spage=323. 
  20. ^ Sant GR, Propert KJ, Hanno PM, et al. (September 2003). "A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis". J Urol. 170 (3): 810–5. doi:10.1097/01.ju.0000083020.06212.3d. PMID 12913705. 
  21. ^ Sand PK, Kaufman DM, Evans RJ, Zhang HF, Alan Fisher DL, Nickel JC (August 2008). "Association between response to pentosan polysulfate sodium therapy for interstitial cystitis and patient questionnaire-based treatment satisfaction". Curr Med Res Opin 24 (8): 2259–64. doi:10.1185/03007990802240727. PMID 18582395. 
  22. ^ Anderson VR, Perry CM (2006). "Pentosan polysulfate: a review of its use in the relief of bladder pain or discomfort in interstitial cystitis". Drugs 66 (6): 821–35. PMID 16706553. 
  23. ^ van Ophoven A, Pokupic S, Heinecke A, Hertle L (August 2004). "A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis". J. Urol. 172 (2): 533–6. doi:10.1097/01.ju.0000132388.54703.4d. PMID 15247722. http://linkinghub.elsevier.com/retrieve/pii/S0022-5347(05)61678-3. 
  24. ^ van Ophoven A, Hertle L (November 2005). "Long-term results of amitriptyline treatment for interstitial cystitis". J. Urol. 174 (5): 1837–40. doi:10.1097/01.ju.0000176741.10094.e0. PMID 16217303. http://linkinghub.elsevier.com/retrieve/pii/00005392-200511000-00038. 
  25. ^ AUA 2002 Abstract - DMSO: Does it change functional properties in the bladder wall Diethild Melchior*, C Subah Packer, Tomalyn C Johnson, Martin Kaefer, Indianapolis, IN
  26. ^ Parsons CL (January 2005). "Successful downregulation of bladder sensory nerves with combination of heparin and alkalinized lidocaine in patients with interstitial cystitis". Urology 65 (1): 45–8. doi:10.1016/j.urology.2004.08.056. PMID 15667861. 
  27. ^ "Prostatitis and Wheat". www.chronicprostatitis.com. http://www.chronicprostatitis.com/wheat.html. Retrieved 2009-11-05. 
  28. ^ Dunn M, Ramsden PD, Roberts JB, Smith JC, Smith PJ (1977). "Interstitial cystitis, treated by prolonged bladder distension". Br J Urol 49 (7): 641–5. doi:10.1111/j.1464-410X.1977.tb04545.x. PMID 597701. 
  29. ^ Erickson DR, Kunselman AR, Bentley CM, et al. (February 2007). "Changes in urine markers and symptoms after bladder distention for interstitial cystitis". J. Urol. 177 (2): 556–60. doi:10.1016/j.juro.2006.09.029. PMID 17222633. 
  30. ^ Peters KM, Carey JM, Konstandt DB (October 2003). "Sacral neuromodulation for the treatment of refractory interstitial cystitis: outcomes based on technique". Int Urogynecol J Pelvic Floor Dysfunct 14 (4): 223–8; discussion 228. doi:10.1007/s00192-003-1070-3. PMID 14530831. 
  31. ^ Fall M, Lindström S (February 1994). "Transcutaneous electrical nerve stimulation in classic and nonulcer interstitial cystitis". Urol. Clin. North Am. 21 (1): 131–9. PMID 8284836. 
  32. ^ Zhao J, Bai J, Zhou Y, Qi G, Du L (June 2008). "Posterior tibial nerve stimulation twice a week in patients with interstitial cystitis". Urology 71 (6): 1080–4. doi:10.1016/j.urology.2008.01.018. PMID 18372023. 
  33. ^ Whitmore KE, Payne CK, Diokno AC, Lukban JC (November 2003). "Sacral neuromodulation in patients with interstitial cystitis: a multicenter clinical trial". Int Urogynecol J Pelvic Floor Dysfunct 14 (5): 305–8; discussion 308–9. doi:10.1007/s00192-003-1080-1. PMID 14618305. 
  34. ^ "Complementary and Alternative Therapies as Treatment Approaches for Interstitial Cystitis", Reviews in Urology (www.pubmedcentral.nih.gov) 4(Suppl 1) (Suppl 1): S28–S35, May 14, 2002, PMID 16986031, http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1476005, "Our experience at the Pelvic Floor Institute shows that IC patients need 10–20 acupuncture treatment sessions in order to achieve symptom relief." 
  35. ^ Rapkin AJ, Kames LD (May 1987). "The pain management approach to chronic pelvic pain". J Reprod Med 32 (5): 323–7. PMID 2439689. 
  36. ^ Geirsson G, Wang YH, Lindström S, Fall M. (1993). "Traditional acupuncture and electrical stimulation of the posterior tibial nerve. A trial in chronic interstitial cystitis.". Scand J Urol Nephrol 27(1): 67–70. PMID 8493470. 
  37. ^ Binder I, Rossbach G, van Ophoven A (July 2008). "[The complexity of chronic pelvic pain exemplified by the condition currently called interstitial cystitis. Part 2: Treatment]" (in German). Aktuelle Urol 39 (4): 289–97. doi:10.1055/s-2008-1038199. PMID 18663671. 
  38. ^ Hsieh CH, Chang ST, Hsieh CJ, et al. (October 2008). "Treatment of interstitial cystitis with hydrodistention and bladder training". Int Urogynecol J Pelvic Floor Dysfunct 19 (10): 1379–84. doi:10.1007/s00192-008-0640-9. PMID 18496634. 
  39. ^ Dell JR, Parsons CL (March 2004). "Multimodal therapy for interstitial cystitis". J Reprod Med 49 (3 Suppl): 243–52. PMID 15088863. 
  40. ^ "Prostatitis Interstitial Cystitis CP/CPPS IC/PBS UCPPS". www.ucpps.org. http://www.ucpps.org/. Retrieved 2009-04-10. 

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