S. Grant Mulholland

Role of surface mucin in primary antibacterial defense of bladder

Histochemical staining of bladder tissue has demonstrated a discrete layer of mucopolysaccharide (mucin) at the surface of rabbit and human bladders. This mucin is disrupted by acid treatment and is probably resynthesized by the transitional cells in less than twenty-four hours and replaced by forty-eight hours. Physiologic data indicate that bladder mucose can resist bacterial attachment, a function that is also disrupted by acid and recovers in less than twenty-four hours. These findings suggest that the surface mucopolysaccharide inhibits bacterial binding and may be the primary antibacterial defense of the urinary tract.

Role of urothelial surface mucoprotein in intrinsic bladder defense

To implicate further the surface mucoprotein as the factor responsible for preventing bacterial attachment to the bladder mucosa, rabbit urothelium was severely disrupted and allowed to regenerate for varying periods of time. Quantitative measurements of the attachment of 14C-labeled Escherichia coli were correlated with the histologic presence of the surface mucoprotein. Control levels of bacterial attachment were observed only when the PAS-positive layer had regenerated, further supporting the role of this layer in the bladders antibacterial defense.

The protective effect of heparin in experimental bladder infection.

Abstract The surface mucopolysaccharide layer of the urinary bladder has been shown to interfere with bacterial attachment, and we therefore consider it to be the primary mechanism of combatting bacterial colonization and subsequent infection. Experimentally, hydrochloric acid alters this layer in such a way as to permit massive bacterial adsorption to the vesical mucosa. Heparin, an acid mucopolysaccharide, was instilled into rabbit bladders that had their naturally occurring mucopolysaccharide altered by hydrochloric acid. Heparin was shown to inhibit the attachment of inoculated Escherichia coli to these acid-treated bladder mucosas, and the degree of protection afforded was similar to that of the mucopolysaccharide layer of the intact urothelium.

Effect of Ammonium on Bacterial Adherence to Bladder Transitional Epithelium

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.

Antisera to a rabbit urinary tract antigen also react with human bladder and kidney tissue.

The mucin layer covering the bladder transitional cell mucosa appears to function as a primary defense mechanism against bacterial infection. We have previously prepared a glycoprotein fraction (GP1) from the urinary bladder mucosa of NZW rabbits and raised murine antisera against it. These antisera react with bladder, ureter and kidney tissue from rabbits, rats, guinea pigs, and hamsters. We now show that a similar substance occurs in human kidneys and bladder. In order to remove antibodies reactive with the Tamm-Horsfall protein (THP), the antisera were initially absorbed with an immunoadsorbent composed of purified human THP covalently bound to Sepharose CL-4B gel. Using an enzyme linked immunosorbent assay (ELISA) it could be shown that the absorbed antisera did not react with THP but retained a high titer in binding to GP1. Immunohistochemical procedures involving avidin-biotin-immunoperoxidase staining demonstrated that the absorbed anti-GP1 reacted well with six human urinary bladder biopsy specimens and two kidney autopsy specimens while normal murine sera showed little or no binding. Although this reactivity was not as strong as that found with homologous tissue (rabbit) these studies suggest that GP1, an antigen common to several animal species, is also related to a human urinary tract component.

Oral Methylene Blue and the Dissolution of Renal Calculi

Oral methylene blue therapy was not effective in dissolving non-obstructive renal calculi in 26 patients but it may prevent new stone formation in patients with metabolically active urolithiasis. The use of methylene blue therapy in combination with other regimens having different mechanisms of stone inhibition is recommended to further improve results.

Partial nephrectomy: Review of 80 cases emphasizing its role in management of localized renal stone disease

Abstract Eighty cases of partial nephrectomy are reviewed with respect to indications for surgery, operative technique, intra- and postoperative complications, and results. In those patients operated on for localized stone disease and followed for an average of 3.9 years, the incidence of ipsilateral new stone formation was 6.3 per cent.

Primary external urethral sphincter hyperkinesia in a boy

Abstract The case presented is an example of urethral obstruction secondary to increased resistance of the external sphincter in a neurologically normal young boy. Unilateral pudendal neurectomy markedly improved voiding pressure-flow patterns in this patient with severe bladder and upper urinary tract disease. The entity of primary external urethral sphincter hyperkinesia, including its cause, diagnosis, and treatment, is discussed.

Antibiotic sensitivity of isolates from nosocomial and community-acquired urinary tract infections

Abstract This report presents the results of antibiotic sensitivity testing of 1,534 urinary tract isolates obtained from hospitalized patients during a twelve-month period. In vitro sensitivities demonstrated that gentamicin was the most effective antibiotic, followed by chloramphenicol and nalidixic acid. Fifty-nine to 61 per cent of the isolates were sensitive to colistin, kanamycin, cephalosporin, and nitrofurantoin. Fewer than half were sensitive to ampicillin, streptomycin, and tetracycline. Bacterial isolates from women with urinary tract infection were significantly more sensitive than those from men. In addition, isolates from community-acquired infections were more sensitive than those of nosocomial origin. This difference in sensitivity suggests the presence of a more antibiotic-resistant hospital flora for the major types of organism.

Two-Stage Urethroplasty for Urethral Stricture Disease

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.