Tamm-Horsfall protein as a marker in interstitial cystitis.

It has been suggested that immunohistochemical staining for Tamm-Horsfall protein in bladder epithelium may be a marker for interstitial cystitis. Of bladder biopsies from 14 interstitial cystitis patients only 3 demonstrated positive staining for Tamm-Horsfall protein within the mucosa, whereas 2 of 11 control biopsies showed positive Tamm-Horsfall protein results. In addition, staining in 4 ureteral specimens from interstitial cystitis patients and 4 controls was negative in all cases. An effort to detect this protein in enterocystoplasty specimens also showed a negative pattern. Our study does not confirm the Tamm-Horsfall protein as permeating either the bladder epithelium in interstitial cystitis or bowel mucosa in enterocystoplasty. This finding does not necessarily mean that these surfaces are not permeable to substances of smaller molecular size, nor does it define whether this is of importance in the etiology of interstitial cystitis. However, it does suggest that this technique does not allow detection of a marker for the disease.     

Tamm-Horsfall autoantibodies in interstitial cystitis

Interstitial cystitis presents a diagnostic and therapeutic challenge. Although many etiologies, including autoimmunity, have been proposed its pathogenesis remains obscure. Tamm-Horsfall protein has been identified in the superficial urothelium of patients with interstitial cystitis demonstrating abnormal urothelial permeability. Eight patients with a clinical diagnosis of interstitial cystitis underwent cystoscopy and bladder biopsy. Characteristic cystoscopic findings were present, and each patient had chronic inflammation and mast cells by histopathological analysis. Preoperative anti-Tamm-Horsfall protein serum antibody (IgG) titers were determined by enzyme-linked immunosorbent assay (range 500 to 8,000, mean 2,750). A control group of 8 patients with a negative urological history also had titers of 0 to 500 (p = 0.02). The humoral response to Tamm-Horsfall protein in these patients suggests a role for Tamm-Horsfall protein in interstitial cystitis. Measurement of serum Tamm-Horsfall protein antibody may prove to be useful as a noninvasive diagnostic test in patients with this disease.     

Interstitial cystitis

Interstitial cystitis (IC) is a multifactorial syndrome with symptoms of pelvic or perineal pain, urinary frequency and urgency. The etiologies are unknown, but several theories have been proposed. Diagnosis is often delayed because most of the conventional evaluation is normal. Pelvic examination is normal except for bladder tenderness. Urodynamics are normal except for increased bladder sensitivity and low capacity. Urinalysis, urine culture and office cystoscopy are also normal. The diagnostic test is cystoscopy under anesthesia with bladder distension. Small submucosal hemorrhages (glomerulations) or ulcers appear after distension. Many empiric treatments have been proposed for IC. None is universally effective, and so treatments are tried sequentially until good symptom relief is achieved. Bladder distension gives excellent (but transient) relief in some patients, especially those with severe bladder inflammation (who also tend to be older). A variety of oral, intravesical and adjunctive treatments are also described.     

Tamm-Horsfall protein acts as a general host-defense factor against bacterial cystitis

AIMS: Tamm-Horsfall protein (THP) is urine's most abundant protein, but its biological function has remained elusive. Recently, THP-deficient (THP(-/-)) mice were shown to have difficulty clearing Escherichia coli from the urinary bladder. It has remained unclear if interaction between THP and E. coli is specific for E. coli or if THP has a versatile ability to clear a variety of bacteria from the bladder, and act as a broad host-defense mechanism against urinary tract infection (UTI). In this study, we examined the role of THP as a protective factor against UTI caused by bacteria other than E. coli, namely Klebsiella pneumoniae and Staphylococcus saprophyticus by determining if the THP(-/-) mouse has difficulty clearing these bacteria from its bladder. METHODS: THP gene knockout mice were generated by the technique of homologous recombination. K. pneumoniae and S. saprophyticus were introduced transurethrally, in separate experiments, into the bladders of the THP(-/-) and genetically similar wild-type (THP(+/+)) mice. Urine was collected at periodic intervals and cultured to quantitate the degree of bacteriuria. Bladders were surgically removed and examined histomorphometrically to determine the intensity of inflammation. RESULTS: Results showed that both with K. pneumoniae and with S. saprophyticus, the THP(-/-) mice had more severe bacteriuria in comparison with THP(+/+) mice. The inflammatory changes in the bladder were also markedly more intense in THP(-/-) mice with each of the bacterial species. CONCLUSIONS: These findings support the hypothesis that THP helps eliminate K. pneumoniae and S. saprophyticus from the urinary tract and acts as a general host-defense factor against UTI.     

Interstitial cystitis.

Twenty histologically proven cases of interstitial cystitis were investigated in an attempt to find evidence of a possible autoimmune mechanism in its aetiology. HLA tissue typing was performed, autoantibody profiles were obtained, and a questionnaire of the patients' past history completed, especially with respect to other autoimmune conditions. An experiment was designed to test the effect of sodium cromoglycate on rat bladders. The results are discussed in relation to the management of patients with interstitial cystitis.     

Interstitial cystitis treated with intravesical doxorubicin

Three patients with interstitial cystitis diagnosed on the basis of clinical symptoms, classic endoscopic findings, and a typical histologic picture were treated with intravesical doxorubicin. All 3 patients showed remarkable improvement, as manifested by complete clearance of irritative bladder symptoms and healing of ulceration. Doxorubicin therefore may be the breakthrough drug for interstitial cystitis.     

Interstitial cystitis in Japan

OBJECTIVE: To determine the prevalence of interstitial cystitis in Japan, and to analyse the diagnostic criteria and treatments most commonly used by Japanese urologists. Materials and methods Questionnaires were sent to 300 urologists at major hospitals, including medical university hospitals, throughout Japan, asking about the number of patients with interstitial cystitis, its epidemiology, diagnosis and therapy. RESULTS: The prevalence of interstitial cystitis was 1.2 per 100 000 patients and 4.5 per 100 000 female patients; the male/female ratio was 1 : 5.8. Most Japanese urologists used two or more diagnostic criteria; bladder biopsy was the most common diagnostic method. Dimethyl sulphoxide instillations and corticosteroids were the most frequently used therapies. CONCLUSION: The prevalence of interstitial cystitis in Japan is markedly lower than that reported in Europe and North America. The reasons for this difference were not only racial but also the lack of awareness among Japanese urologists and patients about interstitial cystitis.     

Interstitial cystitis in men

Interstitial cystitis is an uncommon disease reported predominantly in females. Recently we were involved in the management of 4 men who had the clinical, endoscopic and pathological features consistent with the diagnosis of interstitial cystitis. The rarity of occurrence of the disease in males prompted us to report these cases.     

Interstitial cystitis following colocystoplasty

A case of interstitial cystitis occurring in a patient following colocystoplasty for intractable symptomatology resultant from interstitial cystitis is presented. The recurrence of the inflammatory disease in the transposed colonic patch does not appear to be immunologically mediated in this patient.