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Intrarenal reflux: diagnosis with contrast-enhanced harmonic US.

The objective of this case report is to demonstrate the possibility of visualizing intrarenal reflux (IRR) in children using contrast-enhanced harmonic voiding urosonography (VUS). A 10-month-old girl underwent VUS as part of the work-up of acute pyelonephritis of the right kidney. Before and after intravesical administration of US contrast medium (Levovist) the urinary tract was scanned in harmonic imaging mode. Bilateral vesicoureteric reflux was detected (right grade IV, left grade III). Moreover, at the height of the reflux the right kidney parenchyma turned markedly echogenic, corresponding to massive IRR. The voiding cystourethrography that followed confirmed the results of the VUS.

Contrast Media↗

Production of MCP-1 and RANTES in bladder cancer patients after bacillus Calmette-Guerin immunotherapy.

Bacillus Calmette-Guerin (BCG) therapy induces a local immunological response mediated by cellular immune and inflammatory reactions that enhance its anti-tumor efficacy in bladder cancer. Monocyte chemotactic protein-1 (MCP-1) and the "regulated on activation normal T expressed and secreted" chemokine (RANTES) are potent chemotactic molecules that attract monocytes and memory T cells. MCP-1 and RANTES levels in patients with superficial bladder cancer treated with intravesical instillations of BCG are significantly higher than in untreated cancer patients and controls. In the present study, the subjects were divided into three groups: (1) control subjects; (2) bladder cancer patients who did not receive BCG treatment; (3) bladder cancer patients who received intravesical administration of BCG. No differences in the basal production and expression of MCP-1 and RANTES mRNA were observed between BCG-treated and untreated patients. BCG treatment influenced the monocyte response to phytohemagglutinin (PHA) and BCG stimulation. After 24-h incubation, monocytes from BCG-treated bladder cancer patients released more MCP-1 and RANTES than those from untreated bladder cancer patients and controls. The anti-tumor effects of BCG observed in superficial bladder cancer therapy may depend on stimulation of the investigated chemokines, which attract monocytes/macrophages and memory T cells.

BCG Vaccine↗

Current status of vesicoureteral reflux diagnosis.

In children, diagnostic imaging for vesicoureteral reflux (VUR) encompasses both radiologic and sonographic modalities. The former comprises voiding cystourethrography (VCUG), the most widespread method for examination for reflux, and radionuclide cystography (RNC). In RNC the radiation exposure is significantly less than in VCUG with continuous fluoroscopy, but the anatomic details depicted are much inferior. With the introduction of pulsed fluoroscopy, the radiation exposure of VCUG has been markedly curtailed. VCUG is the first imaging choice for the urethra. The sonographic diagnosis of VUR with the intravesical administration of an ultrasound (US) contrast agent-voiding urosonography (VUS)-is being used increasingly in the routine diagnostic imaging work-up of reflux. Various sonographic reflux examination methods had been tried in the past. The real breakthrough came with the availability of stabilized US contrast media. Further impetus came with the introduction of harmonic US imaging. The recent release of a second generation US contrast medium promises to make a further positive impact on VUS. The diagnostic accuracy of contrast-enhanced VUS has been found to be comparable to radiologic methods. VUS is primarily performed in follow-up studies and as the primary reflux examination modality in girls.

Child↗

Update on overactive bladder: pharmacologic approaches on the horizon.

Limitations exist with regard to the array of available agents for the pharmacologic therapy of overactive bladder, including issues of efficacy and tolerability. It is clear that the ideal agent for this condition has not been identified. However, several new pharmacologic treatments, including some with novel approaches to drug delivery, have emerged in clinical development over the past few years. These agents include a variety of anticholinergics and others. In initial studies, some of the agents appear to compare favorably with existing therapies. Whether these promising results will hold up when subjected to large-scale, well-controlled clinical trials is unclear.

Administration, Cutaneous↗

Inhibition of murine bladder tumor growth by bacille Calmette-Guerin: lack of a role of natural killer cells.

Intravesical instillation of bacille Calmette Guerin (BCG) currently is considered the most effective treatment for recurrent superficial bladder cancer, but little is known about the mechanism of action. We have adapted a model in which the mouse bladder tumor, MBT-2, is implanted directly into the bladder to examine the mechanism by which BCG inhibits tumor growth. The intravesical administration of BCG inhibited MBT-2 implantation in a dose-dependent manner. Concomitantly, natural killer (NK) activity was augmented in a dose-dependent manner. Conversely, BCG doses which did not augment NK activity lacked antitumor activity. Linear regression analysis showed a significant correlation between the antitumor activity of BCG and modulation of NK activity (correlation coefficient, 0.991). Additional studies were performed in which NK activity was abrogated by administration of anti-asialo-GM1 serum. NK activity was depressed in spleens and lymph nodes of both normal and BCG-treated mice. Abrogation of NK activity did not alter the efficacy of BCG therapy suggesting that NK cells are not a major contributor to the antitumor activity of BCG.

Animals↗

Safety and efficacy of intravesical aminocaproic acid for bleeding after transurethral resection of prostate.

There appears to be no clinically significant difference in blood loss or transfusion requirements after transurethral resection of the prostate (TURP) when intravesical 0.5% aminocaproic acid is compared with 0.9% sodium chloride irrigation in patients during the first three days after surgery. This is probably because early post-TURP bleeding is due to inadequate hemostasis or perforation of the prostatic capsule, and not excessive local or systemic fibrinolysis. However, we suggest that intravesical aminocaproic acid might be a useful alternative to systemic antifibrinolytic therapy in patients with delayed, recurrent, excessive post-prostatectomy bleeding, which is thought to be due to fibrinolysis. Since aminocaproic acid is not systemically absorbed after bladder instillation, intravesical administration causes few side effects and does not necessitate screening patients for disseminated intravascular coagulation prior to treatment.

Aged↗

Motor and inflammatory effect of hyperosmolar solutions on the rat urinary bladder in relation to capsaicin-sensitive sensory nerves.

1. Intravesical administration of hyperosmolar NaCl or urea solutions produced a concentration-dependent stimulatory action on the micturition reflex in urethane-anesthetized rats. This effect was not modified in rats pretreated with capsaicin as adults (50 mg/kg s.c. 4 days before). 2. Hyperosmolar NaCl also produced Evans blue leakage (plasma extravasation) in the rat bladder. This effect was greatly reduced by extrinsic bladder denervation and in rats desensitized to capsaicin as newborns but not as adults. 3. Cumulative addition of NaCl produced a concentration-dependent increase in tone and biphasic effects on neurogenic contractions of the rat isolated bladder. These effects were not modified by in vitro capsaicin desensitization. 4. These findings do not support the idea that true osmoreceptors are present in the rat urinary bladder. The neurogenic component of the inflammatory response to hyperosmolar NaCl could involve activation of a subpopulation of bladder sensory fibers susceptible to the neurotoxic action of capsaicin in the early postnatal period only.

Animals↗

Painful bladder syndrome/interstitial cystitis.

Painful bladder syndrome (PBS) is the term used to refer to a chronic symptom complex of urinary frequency and bladder 'pressure', discomfort or pain in the absence of any other reasonable cause for these symptoms (such as infection). Interstitial cystitis (IC) is the established term used by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) consensus workshop for which a research definition was formulated in the late 1980s. Opinion varies regarding not only definition but also the usefulness of diagnostic investigations such as urodynamic assessment and the potassium sensitivity test. There are still controversies concerning the most basic investigation of cystoscopy in PBS/IC. New developments in the study of PBS/IC include the identification of a potential urinary biomarker, antiproliferative factor (APF), which is produced by urothelial cells in IC and thought to inhibit proliferation. In addition, condition-specific validated questionnaires should aid evaluation, and a growing number of randomised controlled trials should enable clinicians to use evidence-based therapeutic options.

Administration, Intravesical↗

Diagnosis and treatment of the overactive bladder.

Overactive bladder syndrome (OAB) is a symptomatic diagnosis based on the presence of urgency, with or without urge incontinence, and usually accompanied by frequency and nocturia, in the absence of obvious pathologic or metabolic disease. Initial management of OAB requires an integrated approach using behavioral and pharmacologic methods. Patients should be educated about the functioning of the lower urinary tract system, fluid and dietary management, timed or prophylactic voiding and bladder training regimens, the keeping of micturition charts or bladder diaries, and pelvic floor exercises. Although the effectiveness of muscarinic receptor antagonists for the treatment of OAB has been shown, adverse effects, such as dry mouth, constipation, and blurred vision have somewhat limited their usefulness. Newer agents that are more bladder selective have been and continue to be developed. The concept of clinical effectiveness-a combination of efficacy, tolerability, and compliance-can be used to evaluate not only how well a drug works, but also the side-effect profile and bothersomeness and how likely patients are to continue treatment. Patients who do not respond to antimuscarinic treatment of OAB may do so because of a variety of nonpharmacologic and pharmacologic reasons. Most cases of OAB are not cured, but rather the symptoms are reduced, with an associated improvement in the patients' quality of life. Patients who have failed behavioral and pharmacologic intervention may respond to neuromodulation and augmentation cystoplasty. Future approaches may include (1) other types of systemic pharmacologic therapy; (2) intravesical administration of drugs, including blockers of afferent input; (3) intradetrusor injection of botulinum toxin; (4) the use of tissue engineering to simplify augmentation cystoplasty; (5) genetic interventions to reverse neuroplasticity changes; and (6) combinations of these approaches.

Algorithms↗

In vivo models of interstitial cystitis.

PURPOSE: We systematically identified and evaluated various animal models that have been studied to help identify the underlying mechanisms of and possible treatment options for interstitial cystitis. MATERIALS AND METHODS: Models of interstitial cystitis published between 1983 and 2001 were obtained by searching MEDLINE and other Internet databases using cystitis and model as the primary key words. Models with characteristics of interstitial cystitis similar to those defined by National Institutes of Arthritis, Diabetes, Digestive and Kidney Diseases criteria were reviewed. Some articles describing animal models with similar pathological conditions in other organs were also included to enlarge the base of potentially relevant material. RESULTS: We identified and evaluated some 16 animal models of interstitial cystitis, which we categorized as bladder inflammation induced by intravesical administration of an irritant or immune stimulant, systemic and environmentally induced inflammation, and a naturally occurring model of interstitial cystitis that occurs in cats. Some abnormalities identified in humans and cats with interstitial cystitis can be reproduced in healthy animals using luminal, systemic or environmental stimuli. At the level of the bladder the source of stimulation cannot be discriminated. Variability in the extent of bladder distention complicated the interpretation of some studies. In addition, the noxious stimuli used can affect many epithelial surfaces as well as the urothelium, suggesting they are nonspecific responses to injury rather than specific to interstitial cystitis. CONCLUSIONS: No model in bladder injury in healthy animals currently reproduces as many features of interstitial cystitis as the naturally occurring disease in cats. While induced models of relative injury may help to provide insight into the bladder response to injury, feline interstitial cystitis follows a similar chronic waxing and waning time course as does interstitial cystitis in humans, which may be more suitable for studying the effects of stressors on the severity of clinical signs as well as newly proposed therapies.

Animals↗

The morphological and functional changes in rat bladder following photodynamic therapy with phthalocyanine photosensitization.

We have studied photodynamic therapy (PDT) in the rat bladder with a new photosensitizer, aluminium sulfonated phthalocyanine (AlSPc) given intravenously and intravesically. The microscopic distribution of photosensitizer fluorescence in the bladder wall was studied by laser fluorescence microscopy. Prior to PDT the bladder capacity and compliance were assessed by filling cystometry. Intravesical red light (675 nm.) from a copper vapour pumped dye laser was used to activate the photosensitizer using light doses of 20 to 200 J/cm2. Urodynamic and histologic changes were studied at intervals for up to three months. The fluorescence studies showed that AlSPc was eliminated from the deeper muscle layers more quickly than from the superficial layers of the bladder wall so that by 24 hours there was four times as much fluorescence from the mucosa and lamina propria compared to the deeper muscle. Control bladders illuminated with laser light alone showed no effects at these light doses. Animals treated 24 hours after sensitization showed a reduction in bladder capacity of up to 78% (20 J/cm2. light and 1.5 mg./kg.AlSPc). An initial reduction in compliance recovered in two weeks after low doses (0.5 mg./kg.) of AlSPc but was still abnormal at three months after higher doses (1.5 mg./kg.); though there was no long term histologic abnormality seen. Aluminium sulfonated phthalocyanine is a promising photosensitizer for bladder photodynamic therapy and using low doses of the drug it is possible to produce a superficial necrosis without muscle damage across a range of light doses. This heals by epithelial regeneration with no long term functional impairment. Direct absorption of this photosensitizer following intravesical administration seems unreliable.

Animals↗

Choice of an optimal diluent for intravesical bacillus Calmette-Guerin administration.

The physical conditions, including diluent pH, salt concentration and duration of bacillus Calmette-Guerin attachment, were determined in in vitro binding assays for soluble and matrix fibronectin. Since soluble fibronectin may block attachment of bacillus Calmette-Guerin to matrix fibronectin in the bladder, the optimal conditions were determined under which matrix fibronectin-bacillus Calmette-Guerin binding was maximal and soluble fibronectin-bacillus Calmette-Guerin binding was minimal. These conditions, which were confirmed in vivo in the murine bladder model, included use of normal saline, pH 7 as diluent for bacillus Calmette-Guerin organisms, with retention of the bacillus Calmette-Guerin suspension for 2 hours.

Administration, Intravesical↗

Experimental cytoxan cystitis and prevention by acetylcysteine.

Cytoxan (cyclophosphamide) given to rats intraperitoneally produced a severe cystitis within four hours with marked inflammatory edema and hemorrhagic ulcerations of the mucosa. An in vivo staining test with methylene blue showed deep staining of the urothelium as has been demonstrated with other types of urothelial injuries; uninjured urothelium does not stain. The cytoxan cystitis is probably not due to cytoxan itself, but to a breakdown product acrolein, an aldehyde appearing in the urine. Rat experiments demonstrated that acrolein instilled intravesically produced a cystitis similar to that found with cytoxan injected intraperitoneally. The cystitis due either to cytoxan or acrolein was prevented by simultaneous intravesical administration of an aldehyde inactivating agent, acetylcysteine (mucomyst).

Acetylcysteine↗

Monitoring intravesical bacillus Calmette-Guerin treatment of bladder carcinoma with flow cytometry.

Flow cytometry of bladder irrigation specimens was studied in 22 patients with low stage bladder carcinoma who were treated by transurethral resection of visible tumor followed in 3 to 5 weeks by a course of intravesical bacillus Calmette-Guerin. The most informative examinations were just before the first bacillus Calmette-Guerin treatment, 6 weeks after completing a 6-week course of treatment (3 months) and at 9 months. Of the patients 10 had recurrent tumors after therapy; recurrence was anticipated correctly by flow cytometry at the 12-week followup examination in 6 of the 10 patients and suspected in another. Of 12 patients who remained clinically free of disease for a minimum of 15 months after bacillus Calmette-Guerin therapy flow cytometry identified correctly 7 at 12 weeks, while 1 had a partial response and the remaining 4 reverted to a negative status at 9 months. Of interest, only 4 of the 22 patients were free of disease by flow cytometry at the start of bacillus Calmette-Guerin treatment despite attempted ablation of the tumor by transurethral resection, suggesting that intravesical administration of bacillus Calmette-Guerin destroys existing carcinoma in situ in some cases.

BCG Vaccine↗