Effect of interstitial cystitis on drug absorption from urinary bladder

Borna disease (BD) is a virus-induced immunopathologic disease of the central nervous system in a variety of species from birds to primates and probably in humans. Severe inflammatory reactions lead to tissue destruction and finally to cortical brain atrophy. After experimental infection of the rat, intraparenchymal CD8+ T cells, MHC class I Ags on Borna disease virus (BDV)-infected neurons, and numerous nerve cell lesions were present. Treatment of BDV-infected rats with the mAb OX-8 directed against CD8+ cells inhibited the immunopathologic reactions and reduced MHC class I Ag expression. Neuronal lesions were minimal and no loss of brain substance could be observed. Because BDV has no acute cytopathic effects, we provide evidence that the presence of CD8+ T cells within the brain parenchyma and the expression of MHC class I Ags on neurons play a major role for immunopathologic brain tissue destruction and virus-infected neurons in vivo can be destroyed by T cell-mediated cytotoxicity.     

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.     

Increased tyrosine hydroxylase immunoreactivity in the locus coeruleus of cats with interstitial cystitis

PURPOSE: Environmental stressors seem to play a role in exacerbation of symptoms of interstitial cystitis (IC), both in cats and in human beings. These observations suggest a role for the sympathetic nervous system in the pathophysiology of IC. To begin to assess the underlying role in IC of the pontine nucleus locus coeruleus (LC), the most important source of norepinephrine in the central nervous system, we compared the intensity of tyrosine hydroxylase immunoreactivity (THIR) in sections of LC obtained from cats with IC and from healthy cats. Cats with IC were studied during quiescent periods in an attempt to avoid the risk of flare-induced activation of the LC. MATERIALS AND METHODS: Six cats diagnosed with IC and six healthy cats were studied. Cats with IC were monitored to ensure that no behavioral or urinary signs attributable to IC had been observed for at least two weeks prior to the study. Cats were euthanized and perfused with 4% paraformaldehyde, after which brainstem tissues were collected. Coronal sections (10 microns) of LC were prepared and examined for THIR. RESULTS: THIR in total LC, parabrachial nucleus and LC complex was significantly greater (p < 0.05) in samples from cats with IC than from healthy cats. CONCLUSIONS: The increased THIR in the LC of cats with IC provides additional evidence for increased sympathetic nervous system activity in patients with IC, even during periods of absence of clinical signs.     

Intestinocystoplasty in treatment of interstitial cystitis

Nine cases of interstitial cystitis treated by intestinocystoplasty are reviewed. The longest follow-up is seventy-eight months. Two patients have since died of unrelated causes. The results reveal seven symptomatic cures and two failures. Long-term renal and vesical function have been well maintained.     

Amitriptyline in the treatment of interstitial cystitis

Limited data and an accumulated body of anecdotal experience with the tricyclic class of antidepressants suggest that this group of drugs (especially amitriptyline) may be an effective treatment modality in nonulcerative interstitial cystitis. Both the ease of administration and the relatively rapid onset of relief make these types of drugs appropriate to consider for first-line therapy after bladder distention has failed.     

Treatment of interstitial cystitis with immunosuppression and chloroquine derivatives

Azathioprine, an immunosuppressive agent, was given to 38 patients presenting with intestinal cystitis. Pain disappeared completely in 22 patients and pollakiuria did the same in 20 patients, including two very severe cases with very contracted bladder. Chloroquine or oxychloroquine, usually combined with salicylate, was given to 22 patients. Pain disappeared in 11 patients and pollakiuria in 4 patients. No effect was noted in 10 patients in the azathioprine group and in 8 patients in the chloroquine group. The remaining patients had partial alleviation. The results are analyzed separately for various grades of severity. Spontaneous cure can be expected only in 11% of cases of interstitial cystitis calculated from a large series. Immunosuppression or chloroquine derivates are indicated for patients who do not respond to other treatments.     

Anterior enterocele following cystectomy for intractable interstitial cystitis

PURPOSE: We clinically define the development of an anterior vaginal wall hernia following cystectomy for the management of intractable interstitial cystitis and establish surgical technique for its correction. MATERIALS AND METHODS: Of 27 women who underwent simple cystectomy and urethrectomy for intractable interstitial cystitis an anterior vaginal wall hernia developed in 3 (71, 56 and 61 years old) at 8, 14 and 16 months, respectively, postoperatively. Clinical appearance was similar to a midline cystocele but it contained bowel contents in the form of an anterior enterocele. Anterior enterocele was associated with vaginal vault prolapse in 1 patient who was treated with transvaginal sacro-spinous colpopexy. Patients with isolated anterior enterocele required a transabdominal approach with mobilization of the intestinal hernia contents and obliteration of the intervaginal abdominal wall space. RESULTS: At 12, 19 and 33 months following reconstruction prolapse has not recurred, and sexual function was restored in 1 patient. CONCLUSIONS: These cases suggest that an extended simple cystectomy performed on women with intractable interstitial cystitis may result in a weakening of the anterior vaginal wall with resultant anterior enterocele formation. When it is associated with vaginal vault prolapse a transvaginal technique may be considered but we prefer a transabdominal approach for an isolated anterior enterocele. Prevention of this entity may be warranted at the time of cystectomy.     

High affinity binding sites for [3H]substance P in urinary bladders of cats with interstitial cystitis

PURPOSE: Pain is a common feature of interstitial cystitis (IC). Although the effects of IC on sensory neuron density have been investigated, its influence on substance P receptor (SPR) numbers and function are not well known. To evaluate the role of SPR in cats with IC, we measured the affinity (Kd), numbers (Bmax), and substrate specificity of binding sites for [3H]SP in urinary bladders of healthy cats and cats suffering from IC. MATERIALS & METHODS: Radioligand binding assays of cat and rat brain, normal cat bladders, and inflamed bladders from cats diagnosed with IC were conducted using [3H]SP to determine SPR affinity and numbers. Binding sites for [125I]SP were identified using autoradiography in slide-mounted frozen tissue sections, and their specificity determined with competition binding studies. RESULTS: In bladder homogenate binding studies, low affinity SP binding sites for [3H]SP were found both in normal and inflamed tissue, whereas high affinity binding sites were found in inflamed bladder tissue only. Based on autoradiographic studies, high affinity binding appeared to be to small blood vessels, and to be specific for substance P, a pharmacology consistent with the neurokinin-1 receptor (NK1R). CONCLUSIONS: Upregulation of NK1R may be part of the pathophysiology of IC, as it is in some other inflammatory diseases. If so, more specifically targeted therapies for IC may become available.     

Epidemiology of interstitial cystitis: a population based study

Mycobacterium sp. strain CH1 was isolated from polycyclic aromatic hydrocarbon (PAH)-contaminated freshwater sediments and identified by analysis of 16S rDNA sequences. Strain CH1 was capable of mineralizing three- and four-ring PAHs including phenanthrene, pyrene, and fluoranthene. In addition, strain CH1 could utilize phenanthrene or pyrene as a sole carbon and energy source. A lag phase of at least 3 days was observed during pyrene mineralization. This lag phase decreased to less than 1 day when strain CH1 was grown in the presence of phenanthrene or fluoranthene. Strain CH1 also was capable of using a wide range of alkanes as sole carbon and energy sources. No DNA hybridization was detected with the nahAc gene probe, indicating that enzymes involved in PAH metabolism are not related to the well-characterized naphthalene dioxygenase gene. DNA hybridization was not detected when the alkB gene from Pseudomonas oleovorans was used under high-stringency conditions. However, there was slight but detectable hybridization under low-stringency conditions. This suggests a distant relationship between genes involved in alkane oxidation.     

The course after ileo-cystoplasty in patients with interstitial cystitis

The results of ileocystoplasty in nine patients with interstitial cystitis were evaluated. In addition to the information obtained from the hospital records, all patients answered a postal questionnaire. No serious complications occurred. Mean follow-up was 95 months (75-125 months). Seven patients were continent, of whom three were practising clean intermittent self-catheterization (CIS). One patient remained stress and urge incontinent in spite of CIS. After an uncomplicated operation one patient died seven years later from unknown causes. Six patients were very satisfied and two fairly satisfied with the outcome of the operation. All would accept a new operation if necessary.     

Lupus interstitial cystitis. Apropos of a case]

The poor results obtained with the use of prosthesis in infrapopliteal arterial bypass grafting for critical limb ischaemia led to the introduction of several types of adjuvant arteriovenous fistula to improve the patency and limb salvage rates in patients who have no suitable autologous vein. The main aim of adjunctive arteriovenous fistula in infrageniculate prosthetic bypass is to accelerate the blood flow velocity through the prosthetic graft above the thrombotic threshold level. Since they are subject of great debate among vascular surgeons, the Authors have briefly reviewed the haemodynamic aspects and results reported with the use of such procedures.     

Cytologic examination of urine from patients with interstitial cystitis

PURPOSE: This study was performed to determine the toxicity and efficacy of external-beam radiotherapy in patients with age-related subfoveal neovascularization. METHODS AND MATERIALS: Between January 1996 and September 1996, 25 patients with a mean age of 70.5 (60-84) years were enrolled. All patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. A total of 25 patients were treated with a total dose of 12 Gy in 6 fractions over 8 days. We used a lens-sparing technique and patients were treated with a single lateral 6-MV photon beam. To assess the risk of radiation carcinogenesis after treatment of age-related subfoveal neovascularization, we estimated the effective dose for a standard patient on the basis of tissue-weighting factors as defined by the International Commission on Radiological Protection (ICRP). The calculations were made with TLD on a male randophantom. The lens dose was found to be 0.217 Gy per fraction. RESULTS: No significant acute morbidity was noted. Visual acuity was maintained or improved in 76% and 80% of treated patients at their 1- and 3-month follow-up examinations, respectively. On angiographic imaging, there was stabilization of subfoveal neovascular membranes in 23 patients (92%) at 3 months after irradiation. CONCLUSION: Our observations on these 25 patients in this study indicate that many patients will have improved or stable vision after radiotherapy treatment with low-dose irradiation.     

Detection of eubacteria in interstitial cystitis by 16S rDNA amplification

OBJECTIVE: To determine what role non-culturable microorganisms play in the etiology of interstitial cystitis (IC). MATERIALS AND METHODS: Thirty patients fulfilling NIH criteria for the diagnosis of interstitial cystitis and sixteen control patients with culture negative urine gave written informed consent and underwent bladder biopsy. Polymerase chain reaction (PCR) using two sets of universal primers for bacterial 16S rDNA was performed on urine from the cystoscope and on a cold cup bladder biopsy specimen. Of the PCR positive bladder biopsies, three patients with interstitial cystitis and three controls were randomly selected and cloned. Ten clones from each were sequenced and putative taxonomic assignments made. RESULTS: 12/26 (46%) IC and 5/12 (42%) control urine specimens and 16/30 (53%) and 9/15 (60%) bladder biopsies were PCR positive, respectively. The bacterial populations in the two patient groups tested appeared to be different based upon analysis of the 16S rRNA sequences. CONCLUSIONS: Both IC and control patients had non-culturable bacteria in their bladders. A random sampling of the two populations revealed that the bacterial populations are different, suggesting a possible link between one or more bacterial species and IC.     

Serum hyaluronic acid in Down''s syndrome

Changes in the emission intensities of ultraweak biophoton emission during the cell proliferation of human carcinoma cell culture (TE9 cell line) were detected using a highly sensitive and low noise measurement apparatus coupled with a flow culture system. In the sampling period of 93 h, the biophoton emission intensity from the culture followed a similar course as that of the growth curve. Spectral analysis of the biophoton emission from the cell culture demonstrated a significant peak at around 530 nm. Our results suggest that the emission intensity mainly depends on the cell population and that this noninvasive technique has a potential role in cancer diagnosis.     

Cystoscopic findings consistent with interstitial cystitis in normal women undergoing tubal ligation

PURPOSE: We test the hypothesis that women without chronic pelvic pain or irritative voiding symptoms do not demonstrate petechial hemorrhages known as glomerulations that are characteristic of patients with interstitial cystitis. MATERIALS AND METHODS: A prospective cohort design was used for examination with cystoscopy and bladder distention of 20 asymptomatic women undergoing tubal ligation. Cystoscopy with the patient under general anesthesia was performed to inspect the bladder mucosa before and after distention at 70 cm. of water pressure for 2 or 6 minutes. Photographs of the right, posterior and left of the bladder surfaces taken before and after the distention were scored on a scale of 1 to 5 using a panel of standards. Five urologists blinded to the source of individual photographs independently evaluated 120 research images interspersed with 46 other pictures from a library containing images from 19 symptomatic patients with and without interstitial cystitis. RESULTS: A total of 20 normal women with a mean age plus or minus standard deviation of 29+/-6 years consented to participate in this trial during laparoscopic tubal ligation. Photographs of bladder sites before and after distention with 890+/-140 ml. were scored as 1.4+/-0.3 (before distention) and 3.1+/-1.1 (after distention) on the scale of 1 to 5. The increase in scores following distention in normal subjects was seen to the same degree and in the same proportion as in patients with symptoms of interstitial cystitis (8 of 19 symptomatic patients in this series met current diagnostic criteria for interstitial cystitis). Slight but significant differences were seen among sites in the bladder but not between 2 and 6-minute distention durations. CONCLUSIONS: Bladder mucosal lesions characteristically associated with irritative voiding symptoms and pelvic pain in patients diagnosed with interstitial cystitis were observed in asymptomatic women.     

Detrusor myopathy: an accurate predictor of bladder hypocompliance and contracture in interstitial cystitis

OBJECTIVE: To determine whether any histological characteristics within the detrusor in cases of early interstitial cystitis (IC) predict the subsequent development of severe symptoms due to bladder contracture. PATIENTS AND METHODS: The detrusor muscle component of bladder biopsies from 21 patients with IC was examined in sections stained with haematoxylin and eosin. Videocystometrography was performed at least 2 months after the biopsy and the patients were then followed up clinically for at least 3 years. RESULTS: The detrusor appeared normal in 13 patients; in eight there was evidence of detrusor myopathy. Patients with biopsies confirming detrusor myopathy were significantly more likely to have hypocompliant bladders than those with normal detrusor muscle histology (P < 0.02). Over the following 3 years, six of the eight patients with detrusor myopathy developed progressively severe symptoms and required subtotal cystectomy and enterocystoplasty. None of the 13 patients without detrusor myopathy required bladder substitution. CONCLUSION: In IC, detrusor myopathy is associated with bladder hypocompliance. Patients with detrusor myopathy appear to have more severe disease and are more likely to progress to bladder contracture requiring substitution enterocystoplasty.     

Prolonged bladder distension: experience in the treatment of detrusor overactivity and interstitial cystitis

Prolonged bladder distension continues to be recommended for the treatment of detrusor instability and other bladder conditions. We have reviewed our experience of the technique. A total of 45 patients have undergone 50 procedures. Only 1 of 29 patients with detrusor instability had sustained improvement. 6 of 7 patients with interstitial cystitis noted improvement, sustained in 3. All the other patients noted some improvement. There was a 20% complication rate. 33 (75%) of the living patients returned questionnaires with 27% feeling that the operation was worthwhile. We feel that prolonged distension of the bladder is unhelpful in the treatment of patients with detrusor instability. Its place in the management of patients with interstitial cystitis and irritative symptoms remains controversial. The place of simple bladder distension should be considered.     

Depolymerization reactions of hyaluronic acid in solution

Samples of microbial sodium hyaluronate were degraded by heating, ultrasonication ultraviolet (UV) and gamma-ray irradiation and enzymatic treatment. The weight-average molecular weight, Mw, of hyaluronate in 0.15 M NaCl and 0.06 M Na2HPO4 was determined by gel filtration with UV detection. The Mw of the degraded samples varied from 8 x 10(4) to 1.38 x 10(6). Depolymerization processes can be described by linear relationship (1/Mw)2 = f(t) in the case of ultrasonic treatment and by non-linear relationships in the cases of heating and UV irradiation at 257 nm. Gamma-ray irradiation and enzymatic treatment caused chemical degradation and depolymerization to oligosaccharides, respectively.