Gilbert J. Wise

Prospective Multicenter Surveillance Study of Funguria in Hospitalized Patients

Although fungal urinary tract infections are an increasing nosocomial problem, the significance of funguria is still not clear. This multicenter prospective surveillance study of 861 patients was undertaken to define the epidemiology, management, and outcomes of funguria. Diabetes mellitus was present in 39% of patients, urinary tract abnormalities in 37.7%, and malignancy in 22.2%; only 10.9% had no underlying illnesses. Concomitant nonfungal infections were present in 85%, 90% had received antimicrobial agents, and 83.2% had urinary tract drainage devices. Candida albicans was found in 51.8% of patients and Candida glabrata in 15.6%. Microbiological and clinical outcomes were documented for 530 (61.6%) of the 861 patients. No specific therapy for funguria was given to 155 patients, and the yeast cleared from the urine of 117 (75.5%) of them. Of the 116 patients who had a catheter removed as the only treatment, the funguria cleared in 41 (35.3%). Antifungal therapy was given to 259 patients, eradicating funguria in 130 (50.2%). The rate of eradication with fluconazole was 45.5%, and with amphotericin B bladder irrigation it was 54.4%. Only 7 patients (1.3%) had documented candidemia. The mortality rate was 19.8%, reflecting the multiple serious underlying illnesses found in these patients with funguria.

CYTOKINE VARIATIONS IN PATIENTS WITH HORMONE TREATED PROSTATE CANCER

PURPOSE We evaluated the immunological response in patients with hormone sensitive and refractory prostate cancer, and untreated benign prostatic hyperplasia (BPH). MATERIALS AND METHODS Serum levels of pro-inflammatory and anti-inflammatory cytokines were measured by enzyme-linked immunosorbent assay in 3 groups of patients. The groups included 18 men with a mean age of 79 years who had hormone sensitive prostate cancer, mean prostate specific antigen (PSA) plus or minus standard deviation 1.03 +/- 2.65 ng./ml. and a mean of 35 months of treatment, 10 with a mean age of 86 years who had hormone refractory prostate cancer, mean PSA 27.52 +/- 42.23 ng./ml. and a mean of 42 months of treatment, and 19 with a mean age of 73 years who had BPH and mean PSA 3.37 +/- 2.47 ng./ml. Results were compared with those in 10 age matched, disease-free controls. In the hormone sensitive group PSA regressed to normal and there was clinical evidence of a response to hormone ablation therapy, including orchiectomy, luteinizing hormone releasing hormone analogue and androgen blockade. Hormone refractory cases had elevated PSA and/or clinical evidence of disease progression. RESULTS Levels of the anti-inflammatory cytokines interleukin (IL)-4, IL-6 and IL-10 were significantly elevated in the hormone refractory group compared with values in the hormone sensitive group (p = 0.02, 0.01 and 0.0001, respectively). Abnormal anti-inflammatory cytokines in hormone resistant cases correlated with elevated PSA, while in the BPH group there was no significant difference from controls. Pro-inflammatory cytokines in the hormone sensitive and resistant groups were not significantly different from those in controls. CONCLUSIONS Our study indicates that in hormone refractory prostate cancer a high level of the anti-inflammatory cytokines IL-4, IL-6 and IL-10 develops that is directly associated with elevated PSA. Changes in the level of anti-inflammatory cytokines when androgen independent cells exist may have an important role in the selection of a subset of hormone insensitive cells. These criteria may be used as a prognostic marker for the response to hormone ablation therapy in men with prostate cancer.

Genitourinary manifestations of tuberculosis

By the 1980s, the availability of antituberculosis chemotherapy reduced the incidence and prevalence of tuberculosis. Changing patterns of population emigration and the development of large pools of immune-compromised individuals reversed the downward trend of tuberculosis. The incidence of genitourinary tuberculosis has remained constant. The manifestations of GU TB can be variable and cause a variety of clinical patterns that mimic other diseases. Adrenal insufficiency, renal disease, obstructive uropathy, and chronic cystitis are not uncommon with TB. The patient with TB may have genital disease that simulates STD or scrotal tumors. Infertility can be caused by GU tuberculosis. Awareness of environmental factors and patient history should alert the urologist to the wide array of clinical findings in the genitourinary system that can be caused by tuberculosis.

Nitrofurantoin: the return of an old friend in the wake of growing resistance.

To re‐evaluate the first‐ and second‐line therapies for treating uncomplicated urinary tract infection (UTI), as although fluoroquinolones are commonly used for this purpose, its level of use is thought to be inappropriately excessive and will eventually have a detrimental impact; thus we hypothesise that nitrofurantoin might be the best choice for this indication, due to its low frequency of use and its high susceptibility rate in common UTI pathogens.

Amphotericin B as a Urologic Irrigant in the management of Noninvasive Candiduria

High urinary colony counts of Candida may develop in patients with prolonged indwelling bladder catheters, multiple antibiotic usage and compromised host resistance. Serum candidal antibody titers may differentiate candidal colonization or early infection from invasive or disseminated infection. The persistence of marked candiduria in the absence of elevated antibody titers or other manifestations of disseminated infection presents a therapeutic dilemma to the urologist. Should the patient be treated with systemic therapy, that is flucytosine or intravenous amphotericin B, or should he be observed until the signs of systemic or renal infection develop? Amphotericin B may be used as a urological irrigant in the management of noninvasive urinary fungal infection. Of 40 patients with persistent candiduria treated with daily irrigations of amphotericin B via a 3-way indwelling urethral catheter or urethral catheter and suprapubic tube for an average of 6 days 37 (92.5 per cent) demonstrated marked reduction or elimination of the candiduria. None of the patients had an adverse reaction. Amphotericin B also has been used as a urological adjuvant to surgical treatment of candidal infection of the kidney and upper tract. It also has a role in the treatment in candidal urethritis. We believe that the timely use of amphotericin B irrigations may prevent the development of disseminated candidal infection.

Genitourinary candidiasis: diagnosis and treatment.

Candida in the urine or surgical wound is a potentially lethal pathogen. Management of 82 patients has provided a rationale for the treatment of these infections. Urine colony counts, serologic findings and clinical observations determine therapy. Amphotericin B irrigants are effective for local infections. Disseminated infections require flucytosine and/or intravenous amphotericin B.

AGING EFFECTS ON CONTRACTILITY OF LONGITUDINAL AND CIRCULAR DETRUSOR AND TRIGONE OF RAT BLADDER

PURPOSE Aging is associated with bladder dysfunction, including difficult voiding and urinary leakage. Voiding involves reduction in the bladder lumen in all dimensions brought about by contraction of the meshwork of longitudinal, circular and oblique layers of detrusor smooth muscles. Most in vitro physiological studies of the effects of aging on bladder function used the longitudinal detrusor. To understand the region specific effects of aging on bladder function the contractile responses of longitudinal and circular detrusor, and trigone segments of the bladder from young and old rats were monitored. MATERIALS AND METHODS These studies were performed using male Fisher 344 rats 6 months (young) and 27 months (old) old obtained through the National Institute on Aging. Each rat was anesthetized and the bladder was isolated. From each bladder a strip of longitudinal detrusor, circular detrusor and trigone was isolated and mounted in an in vitro multi-muscle chamber containing normal physiological solution at 37C. Isometric contractions of the 3 bladder strips were monitored after electrical field stimulation, 120 mM. potassium and 1 to 1,000 microM. bethanechol using a digital oscilloscope. RESULTS In longitudinal detrusor from old rats there was no significant difference in the contractions evoked by electrical stimulation or high potassium but there was a significant reduction in contractions evoked by bethanechol compared with the responses of longitudinal detrusor from young rats. In circular detrusor from old rats there was a significant increase in contractions evoked by electrical stimulation and a slight increase in contractions produced by high potassium but no significant change in contractions evoked by bethanechol compared with the responses of circular detrusor from young rats. In trigone from old rats there was a significant decrease in contractions evoked by electrical stimulation, high potassium and bethanechol compared with young trigone. CONCLUSIONS The reduction in contractions evoked by bethanechol suggests an age related reduction in muscarinic receptors in the longitudinal detrusor of aged rats. An increase in contractions evoked by electrical stimulation without a change in contractions evoked by bethanechol suggests a decrease in compliance caused by an increase in collagen in the circular detrusor of aged rats. A general decline in all contractile responses, including those evoked by high potassium, suggests reduced membrane depolarization in the trigone of aged rats. The effect of aging is specific to different regions and functional components of the bladder, probably due to changes in muscarinic receptors, collagen and depolarization.

An Update on Lower Urinary Tract Tuberculosis

Tuberculosis of the genitourinary tract presents with atypical manifestations. Only 20% to 30% of patients with genitourinary tuberculosis have a history of pulmonary infection. Tuberculosis often affects the lower genitourinary system rather than the kidney. Tuberculosis of the lower genitourinary tract most commonly affects the epididymis and the testis, followed by bladder, ureter, prostate, and penis. Use of bacillus Calmette-Guérin therapy for bladder cancer can cause symptomatic tubercular infections of the lower genitourinary tract. Tuberculosis of the lower genitourinary tract can present with irritative voiding symptoms, hematuria, epididymo-orchitis, prostatitis, and fistulas. Tuberculosis of the seminal vesicles, vas, fallopian tubes, and the uterus can cause infertility. Urinalysis may demonstrate sterile pyuria, hematuria, or albuminuria. Identification of acid-fast bacilli in culture or tissue or by polymerase chain reaction studies is diagnostic. Medical treatment may not result in resolution of symptoms. Surgical intervention and reconstruction of the urinary tract are frequently indicated.

FUNCTION OF M3 MUSCARINIC RECEPTORS IN THE RAT URINARY BLADDER FOLLOWING PARTIAL OUTLET OBSTRUCTION

PURPOSE Partial outlet obstruction of the rat urinary bladder leads to hypertrophy and alteration in contractility of the detrusor muscle involving changes in muscarinic receptors. m3 muscarinic receptor subtype has been known to play a predominant role in contractility of normal urinary bladder. The purpose of the present study was to assess the role of m3 receptors in contractility of the obstructed bladder. MATERIALS AND METHODS In male rats, partial outlet obstruction of the urinary bladder was performed by surgically tying a 6-0 suture around the bladder neck, reducing the diameter of it by 2/3 of the original size. Four weeks after the surgery, the bladders were removed and thin strips were microdissected. Similarly, bladder strips from age matched unoperated normal rats were obtained. Sets of four strips from four normal or four obstructed rats were mounted in an in vitro multi-muscle chamber containing normal physiological solution at 37C. The tension responses evoked by optimal electrical field stimulation at 1, 10, 30, 50, and 100 Hz, and the contracture responses evoked by 120 mM potassium and 0.01 to 300.0 microM carbachol were recorded using a Nicolet digital oscilloscope. Similar responses were recorded in different sets of four strips following exposure to 10 and 100 nM 4-DAMP, which is a muscarinic antagonist with a high affinity for m3 and m1 receptor subtypes. RESULTS The obstructed bladders showed 119% increase in weight. In control physiological solution, the obstructed bladder strips did not show significant difference in electrically-evoked tension or carbachol contractures, but showed significantly lower potassium contractures compared with normal bladder strips. 4-DAMP at 10 to 100 nM significantly reduced the electrically evoked tension responses by about the same degree in normal and obstructed bladders, without affecting the potassium contractures. It significantly increased the EC50 values for carbachol contractures in normal bladder, and to a significantly lesser extent in obstructed bladder. Schild plots using the Hill transformed EC50 values showed that the pA2 value for 4-DAMP was not significantly different in normal and obstructed bladders. CONCLUSIONS Significantly smaller potassium contracture in the obstructed bladder indicates that depolarizability of the detrusor muscle membrane, and consequently the activity of voltage-gated Ca2+ channels may be reduced in the detrusor after partial outlet obstruction. Lack of a significant difference in the effect of 4-DAMP on the electrically evoked tension responses and in the pA2 values for 4-DAMP assessed by carbachol contractures, in normal and obstructed bladder strips, indicates that m3 muscarinic receptors still play a predominant role in causing detrusor contractility in the obstructed bladder, as in the normal bladder.

Correlation of histochemical and biochemical analyses of androgen binding in prostatic cancer: Relation to therapeutic response

A histochemical technique for the detection of androgen binding in prostatic cancer was performed on specimens from 108 patients and compared with a biochemical method in a double blind study of 77. Statistical analyses showed a significant agreement between the two assay systems for the qualitative and quantitative presence or absence of specific androgen binding, as well as for the subcellular localization of binding in nucleus and/or cytoplasm. Although the number of cases studied was too small for statistical analysis, there appeared to be good correlation between histochemical androgen binding results and clinical response, or lack of response to hormonal manipulation in 20 patients with Stage C and Stage D carcinoma. No correlation was evident between androgen binding and tumor grade or clinicopathologic stage of disease by either histochemistry or biochemistry.