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The mucopolysaccharide layer produced by the transitional cells coating the bladder plays an important role in the defense mechanism of the lower urinary tract. Carbenoxolone, a drug derived from licorice, has been shown to be beneficial to patients with peptic ulcer disease by stimulating increased mucous production in the stomach. Since the bladder epithelium has an endodermal derivation, the question of whether carbenoxolone has an effect on the mucopolysaccharide layer in the bladder was put forth. Carbenoxolone was shown to provide a protective effect to laboratory-induced lower urinary tract infections in the rabbit model.

Pre-existing bacteriuria of 2 to 3 weeks' duration in the rabbit had no effect on either the histological integrity of the sialomucin layer (anti-adherence factor) of the bladder mucosa or the protective effect of this layer against super-infection.

The glycolipids of the P blood groups have been isolated from human urothelial cells and have proved to be likely receptor sites for Escherichia coli. The presence or absence of these antigens may be a factor influencing the adherence of bacteria to the urothelial cells. Therefore, an experimental group of 27 infection-prone premenopausal women, ranging in age from seventeen to thirty-six years, received blood group typing in the ABO and P systems. These women were found to have a normal distribution in the ABO system. Eighty-five per cent were found to be the P2 phenotype compared with the expected frequency of 21 per cent in the general population. These data suggest that there is a genetic influence at the cellular level which may make certain women more prone to urinary tract infections and differences in bacterial adherence.

The virulence of urease-producing bacteria depends on the ability of urease to degrade urea into ammonia and thereby to alkalinize the urine. Infections caused by urease-producing organisms such as Proteus mirabilis are particularly difficult to manage clinically. We have shown that the layer of glycosaminoglycans at the bladder surface protects against infection by blocking the adherence of bacteria to the epithelium. To determine whether urease-producing urinary pathogens owe their virulence in part to an ability to inactivate the protective effect of the glycosaminoglycan layer, we tested the ability of ammonium chloride to alter bacterial adherence to the normal vesical mucosa. We used an in vivo adherence assay that we have described previously in rabbits. Control animals received sodium chloride adjusted to the same pH as the ammonium chloride. We found that 0.25 M ammonium chloride significantly increases bacterial adherence to normal vesical mucosa as compared to adherence in controls receiving 0.25 M sodium chloride (p less than 0.05). These data suggest that urease plays a hitherto undescribed role in bacterial virulence by altering the antiadherence activity of the glycosaminoglycan layer present at the transitional cell surface.

We previously reported the results of quantitative and histochemical studies implicating the surface mucin of the bladder mucosa as an important antibacterial defense mechanism, which functions by preventing bacteria from adhering to the bladder wall. We call the mucin "anti-adherence factor" and we feel this is a previously undocumented role for mucin as a type of host antibacterial defense. These experiments were conduced with Escherichia coli. In an effort to determine whether the anti-adherence ability of the vesical mucin was a generalized phenomenon, we repeated these studies using unrelated bacterial species, including E coli, Klebsiella pneumoniae, and Staphylococcus aureus. The ability of the vesical mucosa to resist bacterial adherence to its surface was found to be independent of the bacterial species that was investigated.

In order for micro-organisms to infect the urinary tract they must adhere to the vesical mucosa so that they remain after voiding. Experiments in our laboratory demonstrated that the bladder has a self-protective mechanism capable of preventing bacterial adherence to the surface. Histochemical staining demonstrated that this substance is a mucopolysaccharide. Treatment of the mucosa with acid disrupted the protective layer and resulted in a 20 to 100-fold increase in bacterial adherence. Within 24 hours this layer reappeared and binding was again reduced to normal. This phenomenon was not related to microbial species or metabolic activity.

This paper describes an open assessment of cinoxacin in the treatment of 30 outpatients with symptomatic urinary tract infections caused by Escherichia coli, Klebsiella, Proteus mirabilis, and Enterobacter. Twenty-seven patients (90 percent) had a satisfactory clinical response and in 26 patients, there was a satisfactory microbiological response with elimination of the pathogen. Mild side effects were reported by three patients, none of whom stopped therapy. It is concluded that cinoxacin will be useful in the treatment of urinary tract disease because of the high urinary antibacterial activity produced. The relatively low incidence of side effects and convenience of twice-daily dosage should encourage good compliance by patients treated outside the hospital setting.

We have previusly provided physiologic and histochemical data implicating the bladder surface mucin layer as an important new antibacterial defense mechanism. This mucin or its contents seems to act as an "antiadherence factor", inhibiting bacterial adherence to the bladder mucosa and thereby facilitating the removal of bacteria by the voiding process. The present study was designed to investigate three mechanisms by which the mucin might repel bacterial attachment. Our data suggest that neither IgA nor a chelating agent are anti-adherence factors. We did find, however, that pH had a significant effect on the adherence of bacteria to mucosal cells stripped of their mucin layer. This result suggest that electrochemical charge is important in bacterial adherence. We beleive that the mucin layer both provides an electrochemical coat on the bladder surface that is a poor substrate for bacterial adherence and blocks the receptor sites of the transitional cells to which the microbes might adhere.

One of the primary antibacterial defense mechanisms of the bladder is the action of the luminal mucopolysaccharide layer against adsorption of inoculated bacteria. Previous studies have shown that local instillation of the mucopolysaccharide heparin can prevent bacterial adsorption on the bladder mucosa denuded of this "antiadherence factor". To determine whether this action was due to the mucopolysaccharide composition of heparin, or rather to its anticoagulant property, protamine sulfate (a basic protein with anticoagulant properties) was tested for antiadsorptive efficacy. Protamine offered no protection against bacterial adherence in the rabbit model. It appears that heparin's protective effect is unrelated to its action as an anticoagulant.

The need for better prostate imaging techniques is great. As experience is gained with newer modalities, they will become established and more reliable. In the next few years improvements certainly will be made and there will be significant improvements in patient care.

Forty patients with stage O papillary transitional cell carcinoma of the bladder were tested for the presence or absence of ABH blood group substances. Of 25 tumors with antigens 21 (84 per cent) remained stage O, with a mean followup of 13.3 years. Of 15 tumors devoid of blood group substances 11 (73.3 per cent) progressed to stage B or greater in a mean of 4.3 years. Patients without antigens whose tumor remained stage O were followed for a mean of 10 years. Two patients with initially positive tumors subsequently showed loss of antigens and invasion. In 7 of 8 patients the benign epithelium showed a greater concentration of blood group substances than did the corresponding tumor. The presence or absence of blood group substances can be used to predict the biological behavior of stage O transitional cell carcinoma.

A thirty-two-year-old man presented with a history of infertility, recurrent epididymitis, and a fluctuant pelvic mass on rectal examination. Preoperative evaluation disclosed a nonvisualized right kidney and a multiloculated cystic lesion in the pelvis. The intravenous pyelogram suggested a ureterocele on the right side. A cystic pelvic mass was noted on ultrasound and computed tomography. A dysplastic right kidney with an ectopic ureter inserting into a cystic seminal vesicle was found at surgical exploration.

One of the primary antibacterial defense mechanisms of the bladder is the action of the luminal mucopolysaccharide layer against adsorption of inoculated bacteria. Previous studies have shown that local instillation of the mucopolysaccharide heparin can prevent bacterial adsorption on the bladder mucosa denuded of this "antiadherence factor." To determine whether this action was due to the mucopolysaccharide composition of heparin, or rather to its anticoagulant property, protamine sulfate (a basic protein with anticoagulant properties) was tested for antiadsorptive efficacy. Protamine offered no protection against bacterial adherence in the rabbit model. It appears that heparin's protective effect is unrelated to its action as an anticoagulant.

Sodium pentosanpolysulfate (Elmiron) is a synthetic, sulfated polysaccharide available in an oral form that is excreted into the urine. This drug was used in a double-blind fashion to evaluate its efficacy in the management of symptoms of interstitial cystitis. A dose of 100 mg. 3 times daily was used for a minimum of 4 months and was continued for longer than 18 months in some individuals. A total of 62 patients was evaluated from 2 different medical centers. Subjective improvements were greater in all parameters when the drug was compared to placebo therapy, with significant improvement in pain, urgency, frequency and nocturia. Objective improvement in average voided volumes was greater with the drug than with placebo (p equals 0.009). No significant difference was found between drug and placebo groups in the average number of daily voiding episodes.

The mucin layer covering the transitional epithelium of the bladder is thought to be an anti-adherence substance for bacteria. We describe the use of an immunoperoxidase staining technique to demonstrate the presence of glycoprotein lining the urothelium of both the upper and lower urinary tracts of the rabbit. Antisera against this glycoprotein (GP1) were raised in Swiss-Webster mice. The genitourinary tracts of male and female NZW rabbits were removed and sequentially treated with mouse anti-GP1 sera, biotin-labelled anti-mouse IgG, and an avidin-biotinylated horseradish peroxidase complex. The results demonstrated that an antigenically similar (or identical) glycoprotein covers the distal renal tubules and urothelium of the renal pelvis, ureters, bladder, and urethra, suggesting that it may function as an antibacterial defense mechanism throughout the urinary tract.

Six-thousand-seven-hundred and forty-nine positive urine cultures from a large metropolitan Veterans Administration hospital were analyzed with respect to the organisms isolated and their antimicrobial sensitivities. A "predicted therapeutic efficacy index" was calculated for each antimicrobial agent tested. Gram-negative pathogens accounted for 84% of the infections. Proteus infections outnumbered those due to strains of Escherichia coli. Gentamycin was found to be the most effective antimicrobial agent.

Of 97 patients who underwent first-stage urethroplasty 23 per cent required at least 1 revision. Sixty-seven patients underwent second-stage reconstruction with a 90 per cent success rate. The various factors influencing the outcome of 2-stage urethroplasty procedures are analyzed critically.

Most lower urinary tract infections in women are uncomplicated and are treated by gynecologists or family physicians. The problem patient may require a thorough workup to identify the causative organism or underlying pathology. A hypothetical case example is presented in which Klebsiella is identified as the pathogen. A cephalosporin is administered for seven days with reculture twenty-four hours after completion of therapy. If the urine proves to be sterile, a bedtime regimen is initiated of nitrofurantoin macrocrystals, 100 mg. The objective is to target the bladder with a potent bactericidal agent that will not create resistant bacterial strains or have side effects. After two weeks, dosage is reduced to every other night for two to four weeks. If the patient continues to have recurrences, short-course self-medication is indicated. In addition to the patient with recurrent infections, other problem patients include the patient with nosocomial infection, immunocompromised patients, infants and preschool children, and the elderly.

We herein describe 9 patients with non-opaque calculi and 3 patients with soft tissue filling defects in the renal pelvis studied by ultrasound. The calculi varied in size from 1.5 cm. to staghorn calculi. All stones were imaged satisfactorily by ultrasound, allowing the diagnosis of stone to be made with confidence. Ultrasonic differentiation of renal pelvic filling defects proved to be a simple, reliable, non-invasive method to differentiate these clinically perplexing lesions.

Ninety-two patients with bladder cancer have been treated with combined pre- and postoperative radiation in a Radiation Oncology Study Group (RTOG) Phase I-II study and at Thomas Jefferson University Hospital. Patients with invasive bladder cancer were entered into the study and given low-dose preoperative radiation (500 rad) to the whole pelvis, either on the day of or the day before cystectomy. Following surgery, patients were pathologically staged. Patients with stage B1 (T2) (grade 3 or 4), stage B2 and C (T3) tumors were given 4500 rad in 5 weeks postoperative radiation. Follow-up in the study ranges from a minimum of 24 months to 5 years, with a median of 36 months. Incidence of complications was 15% (14/92). The 4-year actuarial survival (Kaplan-Meier) by stage of disease is 68% for stage B1 (T2) (grade 3 or 4), 78% for stage B2, and 57% for stage C. These survival results appear to be better than those obtained with other approaches of adjuvant therapy and/or surgery in comparable histopathologically staged patients.

We have developed a model in rabbits for quantitatively determining the attachment of microbial organisms to the vesical mucosa. Our data suggest that the bladder has a primary antibacterial defense mechanism that serves to interrupt microbial attachment. This mechanism seems to be secretory, since after destruction with acid, the resistance to microbial binding returns in less than 24 hr.

Hormonal manipulation has been shown to result in less efficient bladder clearance of bacteria. We describe the use of a double antibody technique to semiquantitatively demonstrate the diminution of bladder glycoproteins from the transitional epithelium in oophorectomized rabbits. Rabbit bladder glycoprotein was isolated and used to immunize Swiss-Webster mice. Bladders of normal and oophorectomized rabbits were sequentially stained with mouse antirabbit sera and fluoresceinated goat antimouse antibody. A significant loss of bladder epithelial glycoprotein was evident in oophorectomized rabbits as compared to controls. This study, utilizing a semiquantitative immunologic staining technique, suggests an intact glycoprotein layer is important in the bladder defense mechanism.

The mucopolysaccharide (MPS) layer of the bladder has been implicated as a bacterial anti-adherence factor in previous experimentation. Production of MPS is known to be related to hormones in other systems of the body and probably to the urinary system. Due to the known rising incidence of urinary tract infection in most menopausal females, an experimental model using oophorectomized rabbits was designed. Oophorectomized and control rabbits were observed for their ability to clear their bladder of experimentally induced Escherichia coli 04 infections. There was a 2-fold increase in the mean number of days for clearance of bacteria among oophorectomized rabbits versus control rabbits. Twice as many rabbits cleared their infection within 1 week in the control population versus the oophorectomized population. To further examine the relationship of oophorectomy to urinary tract infection, a group of 1030 female canines in an animal veterinary practice was studied. It was found that the incidence of infection was higher in the spayed population than in the non-spayed group. The non-spayed group seem to have an age dependent history of urinary infection whereas ovariohysterectomy appeared to abolish this relationship to age.

The mucin layer of the bladder covering the transitional epithelium is thought to be an anti-adherence substance for bacteria. We have previously demonstrated that removal of this layer results in increased bacterial colonization. In this present communication we report our attempts to isolate and characterize the components of the mucin layer. Bladders were removed from female NZW rabbits and the mucosal layer was extracted with 0.1 M NaCl. Fractional centrifugation and column chromatography on AcA 34 and AcA 22 resulted in the separation of a partially purified glycoprotein, containing 30% carbohydrate, migrating as a single peak (4.5S) in the analytical ultracentrifuge. It was immunogenic in mice and the antisera were used to develop both a radioimmunoassay and an enzyme linked immunosorbent assay (ELISA). The antigenic activity of the glycoprotein was destroyed by protease or extremes of pH, but not by several glycosidases. In addition the murine antisera could not be inhibited by a panel of naturally occurring glycoproteins or glycosaminoglycans.

An analysis of the systems of nosocomial infection reporting utilized in a 332 bed, urban, referral-type hospital demonstrated that physician reporting was much less reliable than a well-planned surveillance system coordinated by an infection control nurse. During 12 months' experience with the most recently devloped system, the average monthly rate of nosocomial infection was 10.7%. A prevalence survey gave a rate of 14.4%. The efficiency of reporting was close to 100% when the infection control nurse spent 100% of her time on surveillance. With a reduction in surveillance time to 75%, the efficiency of reporting fell to about 75%.