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PubMed1993

Urine laminin P1 assessment discriminates between invasive and noninvasive urothelial cell carcinoma of the bladder.

In a cross-section study the levels of urine laminin P1 expressed as a laminin P1:creatinine ratio were determined in 25 patients with superficial (noninvasive) transitional cell carcinoma (TCC) of the bladder, 12 patients with invasive TCC, 15 patients with inflammatory bladder diseases and 50 healthy controls. The mean of laminin P1:creatinine ratios in invasive TCC patients (4.83 +/- 3.05 U/mol creatinine) significantly differed from those of superficial TCC (2.60 +/- 1.07 U/mol creatinine), inflammatory bladder disorders (2.38 +/- 1.74 U/mol creatinine) and controls (2.47 +/- 0.86 U/mol creatinine) (p < 0.03). At the individual patient level 7 out of 12 patients with invasive TCC, but only 1 out of 25 patients with superficial TCC, showed laminin P1 urine levels above the normal range (0.75-4.18 U/mol creatinine), thus giving a 58% sensitivity and a 96% specificity of laminin P1 urine assessment in the discrimination between noninvasive and invasive disease. Given a 20-24% prior chance of invasive disease at initial diagnosis detection of elevated urine laminin P1 in TCC patients raises the posttest chance of invasive disease to 87.5%.

Adult↗
PubMed2003

Graphical visualization and navigation of genetic disease information.

One of the goals of biomedical scientists in this exciting era of molecular biology is the discovery of novel genes and their relationship to the molecular basis of disease. Part of this information connecting the geno-type to the phenotype is already known and available through hubs such as LocusLink. Although Locus-Link is a valuable resource that organizes curated information around genes and provides links to other online resources, it has not been developed for users to visualize graphically the association between genes and diseases, nor to navigate easily from genotype to phenotype (and back) within the same application. The application we developed, g2p, aims at visualizing graphically and navigating genetic disease information, especially the link between genotype and phenotype. The information displayed comes from a LocusLink query on human genes associated with a known disease (1330 genotypes, 1835 phenotypes, and 2050 associations). This application is based, in part, on the graph visualization package GraphViz. Starting from a disease query, g2p displays the phe-notype view (Figure 1). Alternatively, from a gene query, it creates a genotype view (Figure 2). In the example here, a search on the disease Bladder cancer leads to several genes, including RB1 (Figure 1). The double frame around RB1 indicates that it is linked to more than one disease and thus is "navigable". Following this link leads to the several diseases associated with RB1, including - besides Bladder cancer - Retinoblstoma and Osteosarcoma (Figure 2). The latter disease also has a double frame, indicating that several genes are associated with it.

Computer Graphics↗
PubMed1994

The therapeutic role of sulfated polysaccharides in the urinary bladder.

Polysaccharide therapy for bladder disease is a novel therapy based on the model of bladder mucus activity and the belief that mucus and exogenous glycosaminoglycans (GAG) have protective properties. Interstitial cystitis is the first disease explored for the potential use of polysaccharide therapy, which appears to be effective in some patients with this syndrome.

Animals↗
PubMed1975

[Congenital bulbular urethral constrictures. Pathogenesis and treatment of diseases of the bladder neck and urogenital border regions(author's transl)].

This paper is a survey of the literature concerning diseases of the bladder neck, posterior urethra and the urogenital border region. Urethrographic, uroflowmetric and urethrocystoscopic examinations of more than 200 patients ranging in age from one day to over 70 years demonstrated a clear-cut bulbular urethral constricture in this broad-spectrum disease picture. Its a congenital appearance is explained embryologically. A case analysis allows for classification based on the functional value of the urethral constricture. Diseases of as yet unexplained etiology such as Marion's disease, bladder neck sclerosis, urethral valves and chronic prostatitis-prostatopathy are clarified, based on the demonstrated urodynamics.

Adolescent↗
PubMed1992

Urinary bladder cancer following cyclophosphamide therapy for Hodgkin's disease.

Urinary bladder cancers following prolonged cyclophosphamide therapy are being increasingly reported. We report a case of transitional cell carcinoma of the urinary bladder occurring 12 years after pulse intravenous therapy with cyclophosphamide for Hodgkin's disease. The mechanism of bladder carcinogenesis and the possible role of the uroprotector MESNA in preventing cyclophosphamide induced bladder cancer are discussed.

Cyclophosphamide↗
PubMed1982

Flow cytometry of normal and nonneoplastic diseases of the bladder: an estimate of the false positive rate.

From July 1980 through February 1981, 100 patients with normal or nonneoplastic disease of the bladder were studied by flow cytometry. These patients had a variety of medical problems, including carcinoma of the prostate, benign prostatic hypertrophy, acute and chronic cystitis and carcinoma of other sites. The results showed that inflammation and cystitis affected flow cytometry analysis and could lead to false positive diagnoses under some circumstances. With present criteria we estimate that the false positive rate in a urologic population is an acceptable 2 per cent.

False Positive Reactions↗
PubMed1991

Hydroureteronephrosis after spinal cord injury. Effects of lower urinary tract dysfunction on upper tract anatomy.

The hypothesis that upper tract changes in the absence of vesicoureteral reflux are a function of chronically elevated intravesical pressure has had increasing impact on the management of the lower urinary tract in patients with lower tract dysfunction secondary to neurogenic bladder disease. The application of our growing ability to measure bladder and bladder outlet function objectively and in a more physiologic manner through expanding urodynamic techniques will continue to provide information that can be applied to the diagnosis and treatment of lower urinary tract dysfunction and hydroureteronephrosis after spinal cord injury. Current methods of classifying lower urinary tract behavior have not provided the ability to identify accurately those patients at greatest risk for upper tract deterioration. The application of new techniques and the use of new measures may increase our ability to identify these patients.

Humans↗
PubMed1977

Exogenous estrogens and endometrial carcinoma: review and comments for the clinician.

It is justifiable to have reservations about the significance of the data available at this time on a possible increase in the risk of a patient's developing endometrial cancer if estrogen replacement therapy has been prescribed for her. Hopefully, additional studies currently being conducted will help to clarify the issue further. In the meantime, clinicians need guidelines on the use of estrogen replacement therapy. Estrogen is indicated in the premenopausal woman who has had surgical or radiation castration for treatment of disease. Menopausal women with severe vasomotor instability or atrophic vaginitis should also be considered for estrogen replacement therapy. In the latter situation, topical administration may be adequate. Contraindications to estrogen replacement include undiagnosed vaginal bleeding, breast cancer history of thromboembolic disease, liver disease, uterine leiomyomata, hypertension, diabetes, migraine headaches or gall bladder disease. In patients for whom estrogens are contraindicated, atrophic vaginitis can be treated with local estrogens and vasomotor symptoms with sedatives such as phenobarbital and belladonna. Before estrogen treatment is begun, a medical history and physical examination that look for possible contraindications are required. Obviously, any woman with abnormal uterine bleeding in the menopausal age group requires a procedure that provides tissue for histopathologic examination. Although postmenopausal women taking estrogen may have uterine bleeding related to the hormone, such bleeding cannot be assumed to be due to the therapy and always requires evaluation. The lowest dose effective in controlling a patient's symptoms should be administered, preferably in cyclic fashion. Whether the addition of a progestational compound at cyclic intervals has a beneficial effect on the endometrium is a matter of conjecture at this time. Requirement for continuing therapy should be reevaluated at least on an annual basis and preferably more often. In conclusion, a quote from Graber and Barber is appropriate: "The entire picture of routine postmenopausal estrogen therapy is in a state of complete confusion. We must proceed with circumspection and caution. We need less passion, fewer hypotheses, and more facts."

Estrogens↗
PubMed1997

Stromal and vascular invasion in an human in vitro bladder cancer model.

In transitional cell carcinoma (TCC) of the urinary bladder, disease spread may occur through local invasion of the bladder wall and/or via hematogenous dissemination. Although the metastatic phenotype is well studied, little is known about the mechanisms that determine and regulate secondary dispersion via stromal and vascular routes. The aim of this study was to develop an in vitro system to study TCC invasion using normal human urinary tract stroma in organ culture. Human de-epithelialized urinary tract stromas were seeded with established human TCC cell lines (RT4, RT112, and EJ) and maintained in organ culture at an air-liquid interface for up to 8 weeks. The composite tissues were analyzed immunohistochemically using antibodies to a proliferation-associated antigen, cell adhesion molecules, extracellular matrix components, and cytokeratin isotypes. The phenotype of TCC cell lines maintained as monolayer cultures were compared with the composite tissues to assess the regulatory effects of the stroma. On a normal urothelial stroma, the TCC cell lines proliferated and underwent a degree of differentiation related to the grade of the original tumor. RT4 cells formed a stratified epithelium with low proliferation, some characteristics of urothelial differentiation, and no evidence of stromal invasion over the 8-week culture period. RT12 cells formed a stratified epithelium with limited differentiation and by 2 weeks showed intravasation of the subepithelial capillary bed. Anaplastic EJ cells did not stratify but diffusely invaded the stromal matrix and the superficial vasculature. In conclusion, the urothelial stroma can support cytodifferentiation in vitro and influence the behavior of malignant TCC cells. The model has application for determining genetic and epigenetic factors that influence whether a tumor progresses by local and/or hematogenous spread. Furthermore, it may offer a useful approach in evaluating prognostic and diagnostic markers and strategies for preventing invasion.

Antibodies, Monoclonal↗
PubMed2002

[Cystic cystitis in children].

Cystic cystitis is a common urinary bladder disease with a histologic picture of nodular lesions of the bladder mucosa. Intralesional lymphoid proliferation due to recurrent urinary tract infection play a major role in the occurrence of cystic cystitis. It is often found together with vesicoureteral reflux and other urinary tract anomalies and urodynamic disturbances. Examination of 116 children with cystic cystitis revealed it to be associated with urinary tract anomalies, especially vesicoureteral reflux. The average age at diagnosis is 7 years. The disease often needs longterm prophylaxis for urinary tract infections, and has favorable prognosis.

Adolescent↗
PubMed2001

Sensitivity and specificity of antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor as urine markers for interstitial cystitis.

We previously determined that the urine of interstitial cystitis (IC) patients specifically contains a factor (antiproliferative factor [APF]) that inhibits primary bladder epithelial cell proliferation, and that it has significantly decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and increased levels of epidermal growth factor (EGF) compared with urine from asymptomatic controls and patients with bacterial cystitis. We sought to confirm the specificity of these findings for IC using a larger patient population, including control patients with a variety of urogenital disorders. Clean catch urine specimens were collected from 219 symptomatic IC patients, 113 asymptomatic controls without bladder disease, and 211 patients with various urogenital diseases including acute bacterial cystitis, vulvovaginitis, chronic nonbacterial prostatitis, overactive bladder, hematuria, stress incontinence, neurogenic bladder, benign prostatic hyperplasia, bladder or pelvic pain without voiding symptoms, bladder cancer, prostate cancer, or miscellaneous diagnoses including anatomic disorders. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and EGF levels were determined by enzyme-linked immunosorbent assay. APF activity was present significantly more often in IC than control urine specimens (P <0.005 for IC vs any control group; sensitivity = 94%, specificity = 95%, P <10(-82) for IC vs all controls). HB-EGF levels were also significantly lower and EGF levels significantly higher in IC urine than in specimens from controls (P <10(-84) and P <10(-36), respectively). These findings confirm the utility of APF, HB-EGF, and EGF as markers for IC. Understanding the reasons for altered levels of these markers may lead to understanding the pathogenesis of this disorder.

Adult↗
PubMed1987

Construction of a low pressure reservoir and achievement of continence after "diversion" and in end stage vesical dysfunction.

Creation of a continent low pressure urinary reservoir was attempted in 33 patients: 11 with a supravesical diversion, 6 with a vesicostomy, 9 treated by catheter drainage and 7 with end stage bladder disease. The common problems were poor urine storage associated with bladder fibrosis, defunctionalization and decentralization or spinal cord injury coupled with a poorly functional urethral continence mechanism. The over-all outcome at a mean of 21 months (range 4 months to 11 years) was excellent in terms of upper tract function, reservoir capability and continence.

Adult↗
PubMed1982

Bethanechol chloride and the traumatic cord bladder.

The effect of bethanechol chloride was evaluated in 28 men with neurogenic bladder disease secondary to traumatic spinal cord damage. Simultaneous measurements of bladder pressure, electromyography of the pelvic floor and flow rate were obtained to evaluate the effect on voiding. The results of these studies revealed that bethanechol chloride failed to improve voiding dysfunction in these patients in either the supine or sitting position. Functional bladder outlet obstruction was aggravated by bethanechol chloride. It was found that the effect of this drug on the bladder was unpredictable, as evidenced by some patients converting from a definite detrusor contraction to a wave type pattern. Bethanechol chloride failed to induce a detrusor contraction in patients with areflexia or wave pattern bladders.

Adult↗
PubMed2001

Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent.

BACKGROUND: Infliximab is a humanized antibody against tumor necrosis factor alpha (TNF-alpha) that is used in the treatment of Crohn's disease and rheumatoid arthritis. Approximately 147,000 patients throughout the world have received infliximab. Excess TNF-alpha in association with tuberculosis may cause weight loss and night sweats, yet in animal models it has a protective role in the host response to tuberculosis. There is no direct evidence of a protective role of TNF-alpha in patients with tuberculosis. METHODS: We analyzed all reports of tuberculosis after infliximab therapy that had been received as of May 29, 2001, through the MedWatch spontaneous reporting system of the Food and Drug Administration. RESULTS: There were 70 reported cases of tuberculosis after treatment with infliximab, for a median of 12 weeks. In 48 patients, tuberculosis developed after three or fewer infusions. Forty of the patients had extrapulmonary disease (17 had disseminated disease, 11 lymph node disease, 4 peritoneal disease, 2 pleural disease, and 1 each meningeal, enteric, paravertebral, bone, genital, and bladder disease). The diagnosis was confirmed by a biopsy in 33 patients. Of the 70 reports, 64 were from countries with a low incidence of tuberculosis. The reported frequency of tuberculosis in association with infliximab therapy was much higher than the reported frequency of other opportunistic infections associated with this drug. In addition, the rate of reported cases of tuberculosis among patients treated with infliximab was higher than the available background rates. CONCLUSIONS: Active tuberculosis may develop soon after the initiation of treatment with infliximab. Before prescribing the drug, physicians should screen patients for latent tuberculosis infection or disease.

Adolescent↗
PubMed1991

The S-bladder, an ileal bladder substitution.

Low pressure continent urinary diversions with abdominal wall stomas alike the Kock-pouch have shown good results. However, if urethral function can be saved without risk, an anastomosis of a bowel bladder to the urethral stump is more favorable in regards of continence, ease of the procedure and cosmetics. The S-bladder developed on the basis of the S-pouch from Parks, is conceptualized to be a complete replacement of the lower urinary tract, offering a low pressure reservoir, safe antireflux mechanisms, continence and voiding per urethra with abdominal straining. 52 patients (46 males and 6 females) were treated with an S-bladder. Continence in daytime and nighttime was achieved in 44 patients, while 49 patients remain continent during the day. To achieve this result 16 of our patients had to be treated with an artificial sphincter implanted at the bulbous urethra. Eleven of these 16 patients suffered from neurogenic bladder disease with preoperative urethral incompetence. Indications was TCC of the bladder in 38, neurogenic bladders in 11 and low-compliance bladders in 3 patients. The complication rate of 13.5% was acceptable. Emptying by abdominal straining was possible in all patients. Residuals were less than 50 cc, even in those patients with artificial sphincters.

Carcinoma, Transitional Cell↗