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Lower urinary tract symptoms in patients with Sjögren's syndrome and systemic lupus erythematosus.

Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are autoimmune diseases which have many similarities with interstitial cystitis (IC), a urinary bladder disease with unknown etiology. This survey on the occurrence, severity and nature of lower urinary tract symptoms among patients suffering from SS or SLE showed that these patients have significantly more urinary complaints, especially irritative bladder symptoms, than age- and sex-matched controls. We studied 36 patients with SS, 85 patients with SLE and 121 controls. In these groups, 25%, 29% and 66%, respectively, were free of urinary symptoms. The prevalences of mild symptoms were 61%, 62% and 27%, and severe symptoms 14%, 9% and 7% in the respective groups. SS and SLE patients with urinary complaints reported mostly urinary frequency (27% and 62%) and suprapubic pain (36% and 34%). The most common symptom in the control group was stress urinary incontinence. The frequency of lower urinary tract problems in patients with SS and SLE supports the concept that autoimmune disorders also have bladder affections.

Adult↗

Critical review of the models to study the biologic progression of bladder cancer.

For transitional cell carcinoma of the bladder, clinical data indicate that invasive, metastatic tumors can arise through at least two different progression pathways. The majority of invasive, metastatic bladder neoplasms clinically present de novo, i.e., the patients have no history of malignant bladder disease. This implies that the highly malignant tumor cells either arise de novo or have undergone a rapid progression. Alternatively, a considerable fraction of patients with superficial bladder cancer process to invasive disease after a history of relatively benign superficial TCC. The molecular and cell biological basis of tumor progression is only poorly understood. Clearly, a better understanding of this progress could have profound clinical implications, since patients with superficial TCC with a high risk for progression would have to be treated more aggressively. We discuss the problems that are associated with tumor biological studies on early steps in the progression of TCC, especially from a "model system point of view."

Animals↗

Ontogeny of the rat bladder: smooth muscle and epithelial differentiation.

The sequential expression of smooth muscle and epithelial markers in the rat bladder has been defined. Smooth muscle differentiation, based on cell morphology and immunohistochemical localization of smooth muscle alpha-actin, myosin, vinculin, desmin, vimentin and laminin, begins at 16 days of gestation (birth = 22 days) in the rat bladder. Smooth muscle cell differentiation begins in the periphery of the bladder mesenchyme immediately subadjacent to the serosa and continues toward the urothelium. The cytokeratins 5, 7, 8, 14, 18, and 19 are expressed in the bladder epithelium as a function of developmental age with cytokeratin 7, 8, 18, and 19 being coexpressed at 15 days' gestation followed by cytokeratin 5 at 17 days' gestation and cytokeratin 14 in the newborn bladder. An understanding of the ontogeny of both smooth muscle and epithelial differentiation markers in the normal bladder will allow us to study events that occur in the diseased bladder.

Animals↗

Comparative morphometric study of bladder detrusor between patients with benign prostatic hyperplasia and controls.

PURPOSE: We determined the change in the amount of connective tissue of the detrusor in patients with benign prostatic hyperplasia (BPH) in relation to the degree of bladder hypertrophy by ultrasound estimated bladder weight. The ratio of connective tissue-to-smooth muscle between controls and BPH cases was compared. MATERIALS AND METHODS: For normal controls we used cadaver bladders excised at autopsy from 13 men with no urinary tract diseases. Bladder wall samples were also obtained at subcapsular prostatectomy for BPH in 26 patients. On thin sections stained with Masson trichrome, the ratio of connective tissue-to-smooth muscle was measured using a computer assisted color image analysis. This ratio was compared in BPH cases with estimated bladder weight, which was measured preoperatively using transabdominal ultrasonography. RESULTS: A connective tissue-to-smooth muscle ratio ranged from 19.8 to 28.2% (mean plus or minus standard deviation 24.7+/-2.4) and from 12.9 to 53.3% (27.3+/-9.9) in control and BPH cases, respectively. In BPH cases a significant correlation was noted between estimated bladder weight and connective tissue-to-smooth muscle ratio (r=0.788, p <0.0001). Interestingly, in BPH cases with an estimated bladder weight of less than 60 gm. the ratio ranged from 12.9 to 30.4% (22.8+/-4.9), which was not significantly different compared to control cases. In contrast, in all BPH cases with an estimated bladder weight of 60 gm. or more connective tissue-to-smooth muscle ratio increased significantly to more than 30% (range 33.4 to 53.3%, mean 42.2+/-13.6%). CONCLUSIONS: These results suggest that abnormal increase of connective tissue in addition to smooth muscle hypertrophy and/or hyperplasia could contribute to advanced bladder hypertrophy caused by infravesical obstruction.

Aged↗

Role of urinary beta-glucuronidase in human bladder cancer.

It has been suggested that high levels of urinary beta-glucuronidase may increase an individual's risk of bladder cancer by releasing free carcinogens from their inactive glucuronide conjugates in the bladder. The hypothesis derives in part from the high levels of urinary beta-glucuronidase observed in bladder cancer patients. Because most of the individual variation in levels of urinary beta-glucuronidase and other lysosomal enzymes in the normal population is genetically determined, we would expect that, if high glucuronidase levels were a predisposing factor in the disease, bladder cancer patients would transmit this trait to their progeny. We have tested this hypothesis and find that levels of urinary beta-glucuronidase and three other lysosomal enzymes, alpha-galactosidase, beta-galactosidase, and beta-hexosaminidase, are not significantly elevated in 34 progeny of bladder cancer patients compared to 34 matched controls. Additionally, 15 bladder cancer patients judged to be disease free for a median time of 5 years did not have elevated levels of urinary beta-glucuronidase when compared to a normal population of 125 individuals. Thus, the high levels of glucuronidase observed in bladder cancer patients are most likely a consequence of disease rather than a cause.

Adult↗

Gastric and gall bladder emptying of a mixed meal are not coordinated in liver cirrhosis--a simultaneous sonographic study.

BACKGROUND AND AIM: An impaired contractility has been suggested as a contributor to the increased incidence of gallstones in liver cirrhosis, but the few studies on gall bladder emptying in cirrhotics offered contradictory results. Ingestion of a meal triggers the physiological pathway of gall bladder emptying; therefore, it was decided to analyse postprandial kinetics by investigating simultaneously the rates of gastric and gall bladder emptying of a mixed meal in patients with liver cirrhosis. METHODS: Gastric and gall bladder emptying were measured using ultrasound techniques after a solid-liquid meal (14 g fat, 425 kcal) in 24 patients with liver cirrhosis and in 12 controls. None of the subjects had gall bladder disease. Sequential changes in cross sectional area of the gastric antrum and in gall bladder volume were represented as a monoexponential process after the test meal. Cirrhotic patients were analysed according to the severity of disease (Child classes). The presence of portal gastropathy was assessed by endoscopy. Differences between groups were assessed using the two tailed Student's t test for unpaired observations and the correlations by linear regression (Pearson's coefficient). RESULTS: It was found that gastric emptying after the solid-liquid meal was delayed in cirrhotic patients compared with controls. Gall bladder emptying was significantly diminished in cirrhotic patients: the area under curve was greater in Child A (p = 0.01), Child B (p = 0.04), and Child C (p = 0.014) cirrhotics compared with controls. No correlation was found between the variables of gastric and gall bladder emptying. Gall bladder refilling began earlier in cirrhotics than in controls, before completion of gastric emptying. CONCLUSIONS: These results indicate the lack of coordination between gastric and gall bladder emptying in liver cirrhosis. They also support the hypothesis that diminished gall bladder contractility might contribute to the increased gallstone formation in liver cirrhosis.

Female↗

[Bladder accommodation disorders in children with posterior urethral valves].

On the basis of 8 special cases, the authors draw attention to the role of pathology of the bladder itself in the aetiogenesis of residual dilatations of the upper urinary tract after endoscopic treatment of posterior urethral valves. This pathology is dominated by impaired accommodation of the bladder with hypertonicity during filling. It is a second bladder disease, residual after section of the valve. The diagnosis may be made on the basis of two arguments: --narrowing of the upper tract when the bladder is kept permanently drained (in the absence of any vesico-ureteral reflux); --data from urodynamic examination (confirming the absence of any residual obstructive pathology in the cervico-urethral canal). The effects upon the upper urinary tract of this impaired vesical accommodation may be demonstrated by simultaneous urodynamic studies of the upper and lower urinary tract, but in practice urography findings (comparison between full bladder and empty bladder) and those of urodynamics are sufficient to make the diagnosis. It is thus possible to avoid an erroneous diagnosis of primary obstruction of the terminal ureter or of residual cervico-urethral obstructive pathology. This in turn avoids useless and dangerous ureterovesical reimplantations, endoscopic procedures involving the bladder neck or so-called residual valve tissue which no longer exists. Therapeutic approaches are reviewed. The respective roles of urinary bypass and of enterocystoplasty have not yet been clearly defined.

Adolescent↗

[Ovulation inhibitors: the significance of estrogen dose].

The large prospective studies on adverse effects of oral contraceptives have unanimously revealed an increased risk of thromboembolic diseases, which seem to be associated with the dose of ethinylestradiol (EE). According to the recommendations of several medical committees, the dose of EE has, therefore, been more and more reduced; in some countries there are now ovulation inhibitors containing 20 micrograms EE. Since serious reactions, which have a relatively low incidence, are highly underreported (less than 10%), it is difficult to prove dose-dependent differences in the rates of cardiovascular diseases. There is, however, virtually no doubt that not only the incidence of thromboembolic diseases and stroke, but also that of benign liver tumours and gall bladder diseases is increased in relation to the EE-dose. A series of metabolic serum parameters, e.g. serum binding proteins, coagulation and fibrinolysis factors, angiotensinogen, is changed by EE in a dose-dependent manner which is, however, limited when the effects are receptor-mediated. Higher doses of EE have been shown to facilitate fibrin deposits on vascular subendothelium. The pharmacological effects of EE are to a large extent dependent on the dose, e.g. the irreversible reactions of EE and other ethinylated steroids with hepatic enzymes which are involved in the metabolism of steroids, drugs and toxic compounds. After long-term treatment with combinations containing 50 micrograms EE, in half of the women, abnormal liver function tests with pathological morphological alterations have been found. As combinations with low EE doses and a sufficiently effective progestogen component do not differ from higher dosed oral contraceptives in their contraceptive safety and cycle control, there are no indications for pills containing 50 micrograms EE, except the normophasic sequential preparations for women with sustained irregular bleedings when taking low dose combinations.

Contraceptives, Oral, Hormonal↗

Detection of tumorigenesis in rat bladders with optical coherence tomography.

Optical coherence tomography (OCT) is a novel technique that enables noninvasive cross-sectional imaging of biological tissues. Because of its high resolution (approximately 10 microm), superior dynamic range (140 dB in our case) and up to 2-3 mm penetration depth, OCT is potentially useful for noninvasive screening of superficial lesions. Bladder cancer arises within the transitional epithelium. Despite the ability to visualize the epithelium via cystoscopy, it is often difficult to detect early epithelial cancers and to determine their penetration to the underlying layers. To investigate the potential of OCT to enhance imaging of bladder cancers and other epithelial lesions, we applied OCT to normal and diseased bladder epithelium, and correlated the results with histological findings. OCT images of porcine bladder (a close homolog of human bladder) confirm the ability of this method to image human tissues. To determine whether OCT can track the course of bladder cancer, a standard rat model of bladder cancer in which Fisher rats are exposed to methyl-nitroso-urea (MNU), was followed both with OCT and histological studies. Our results show that the micro morphology of porcine bladder such as the urothelium, submucosa and muscles is identified by OCT and well correlated with the histological evaluations. OCT detected edema, inflammatory infiltrates, and submucosal blood congestion as well as the abnormal growth of urothelium (e.g., papillary hyperplasia and carcinomas). By contrast, surface imaging, which resembles cystoscopy, provided far less sensitivity and resolution than OCT. This is the first OCT study of any tumor documented in a systematic fashion, and the results suggest the potential of OCT for the noninvasive diagnosis of both bladder inflammatory lesions and early urothelial abnormalities, which conventional cystoscopy often misses, by imaging characterization of the increases in urothelial thickening and backscattering. However, because of the depth limitation, OCT may have limited applications in staging the invasion of higher-state urothelial cancers, especially for papillary carcinomas.

Animals↗

[Hypogastric artery embolization as a palliative treatment for bleeding secondary to intractable bladder or prostate disease].

OBJECTIVES: Bleeding secondary to severe vesicoprostatic pathology (mainly neoplasic disease and radiation cystitis) may be a serious clinical management problem due to its morbidity and associated increased resources demand in the form of admissions, transfusions and other measures. We review a series of patients embolized for this purpose, its efficacy, tolerability and adverse events. METHODS: We review 8 patients who underwent hypogastric arteries embolization between July 1998 and December 2001, analyzing indications, efficacy and duration, tolerability, and consequences. Right femoral artery access was undertaken in all except one case that needed bilateral femoral accesses. Embolization was achieved by means of coils and particles. All procedures were performed under local anaesthesia. RESULTS: 9 procedures were performed in 8 patients. 3 patients presented with hematuria due to radiation cystitis, 3 from prostatic carcinoma, and 2 with urethrorragy from urethral relapses after cystectomy. 7/9 embolizations were effective achieving immediate complete or almost complete bleeding control; in one case control was partial; another one had limited or no effect. Selective embolization of distal arteries was performed in 3 cases; all the remainders underwent direct hypogastric trunk embolization sparing the superior gluteal artery. Effect lasted between 1 and 31 months. 4 patients died, 3 of them without haematuria, 1 because of an intercurrent disease, and the others from disease progression. 2 patients underwent posterior surgery, one due to recurrent haematuria, and the other, a case of urethral tumour, due to partial failure; partial cystectomy and urethrectomy were performed respectively. 2 patients needed administration of morphic derivatives after embolization, all the others were managed with magnesium metamizol. Only one patient referred mild transitory gluteal claudication. CONCLUSIONS: Percutaneous arterial embolization is an effective instrument to treat patients with haematuria or urethrorragy and severe lower urinary tract pathology in whom curative treatments are not applicable due to their general status, life expectancy, or tumor status.

Adult↗

Ultrasound studies of the effect of trospium chloride on gall-bladder kinetics.

In a randomized double-blind study the effects of increasing doses of trospium chloride (Spasmo-lyt, CAS 10405-02-4), 0.2, 0.5, 1.0, and 1.5 mg i.v., on gall-bladder contractility were compared among themselves and against placebo and n-butylscopolamine bromide (20 mg i.v.) by an intraindividual 5-fold crossover technique. Gall-bladder volumes after drug-induced contraction (fat stimulus with sodium iopodate) were measured by ultrasound scanning conducted by a single examiner. Serial measurements, carried out in 6 female subjects without any evidence of gall-bladder disease, demonstrated a dose-dependent trend of inhibition of gall-bladder motility produced by trospium chloride. In the maximal doses employed (1.0 and 1.5 mg i.v.) trospium chloride effected almost total inhibition of motility. The response to n-butylscopolamine bromide tested in a nonblind comparison, showed a dose-effect ratio of roughly 40:1 between trospium chloride and n-butylscopolamine bromide given intravenously. This work confirms that ultrasound measurement of gall-bladder volume is a suitable pharmacodynamic model for testing the dose-effect relationships of antispasmodic agents.

Benzilates↗

Electromyographic evaluation of human detrusor muscle activity in relation to abdominal muscle activity.

Simultaneous electromyographic (EMG) recordings from the bladder detrusor muscle and the inferior rectus abdominis muscle were made in six normal subjects, in four patients with lower motor neuron bladder disease and in two patients with an upper motor neuron type of bladder lesion. Results of the study demonstrate that the bladder electrodes do not record remote muscle activity from the abdominal muscles so that any increased detrusor electrical activity with abdominal contraction must have some other explanation such as a possible abdominal-detrusor reflex or the production of increased intra-abdominal pressure from abdominal contraction. The study also demonstrates that the detrusor EMG is of value in studying the physiology of the bladder in humans, is a safe and simple technique and is of value particularly in assessing neurogenic bladder disorders.

Abdominal Muscles↗