Bacterial biofilms and catheters in experimental urinary tract infection.

Employing in vitro and in vivo models of catheter-associated infection, biofilm formation of Pseudomonas aeruginosa in artificial urine and bactericidal activity of several classes alone or in combination with a macrolide antibiotic were investigated. In the course of continuous urine flow, bacteria adherent to a Teflon catheter formed microcolonies at 6 h and a biofilm at 24 h. Following 24 h of urine flow, the thickness and the density of the biofilm increased to about 20 microm and 10(8) cfu/mm3, respectively. Of the antibiotics examined, the fluoroquinolones showed the most potent bactericidal activity against the P. aeruginosa biofilms. However, those antibiotics were not always potentiated by the combination with a macrolide antibiotic.

In vitro bactericidal activities of beta-lactamases, amikacin, and fluoroquinolones against Pseudomonas aeruginosa biofilm in artificial urine.

OBJECTIVES: To compare bactericidal activities of antimicrobial agents against Pseudomonas aeruginosa biofilms by employing an in vitro model of catheter-associated infection because such infections are refractory to antimicrobial treatment. METHODS: Bactericidal activities of piperacillin (PIPC), ceftazidime (CAZ), panipenem (PAPM), amikacin (AMK), ciprofloxacin (CPFX), and levofloxacin (LVFX) were examined against a P. aeruginosa biofilm generated on a Teflon catheter in artificial urine. The colony-forming activities of biofilm bacteria were determined for 48 hours during the treatment with each drug at concentrations of 1 up to 128 times the minimal bactericidal concentration (MBC), and time-kill curves were constructed by plotting the viable cell counts against time. RESULTS: Although CAZ was more bactericidal to the biofilm bacteria than PIPC, the biofilm bacteria still remained on the catheter during CAZ treatment at a concentration 128 times the MBC for 48 hours. Biofilm bacteria were completely eradicated within 48 hours by treatment with PAPM and AMK at a concentration 64 and 128 times the MBC, respectively. Both CPFX and LVFX eradicated biofilm bacteria completely by 24 hours at a concentration 32 times the MBC. CONCLUSIONS: These results indicate that fluoroquinolones have the most potent bactericidal activity against the P. aeruginosa biofilm generated in urine.

Possible metastatic routes via portacaval shunts in renal adenocarcinoma with liver metastasis.

Renal adenocarcinoma findings from autopsies on patients with and without liver metastasis (635 and 936 patients, respectively) were investigated concerning the mode of metastasis. The patients with liver metastasis showed a significantly higher frequency of metastases to the lungs, lymph nodes, contralateral kidney, adrenals, pancreas, spleen, peritoneum, and intestines; in the female patients, those with liver metastasis had a higher frequency of metastasis to the ovary and uterus than patients without liver metastasis. Some of the metastases to those organs are explainable by venous spread via portacaval shunts as well as ordinary hematogenous or lymphogenous spread, especially, those to the contralateral kidney, adrenals, spleen, intestines, or ovary.

[The role of serum IgG antibody of Chlamydia trachomatis in urogenital tract diseases].

In the present study, the frequency of antigen and the titer of serum IgG antibody for Chlamydia trachomatis in non-gonococcal urethritis and prostatitis and the variation in the titer of serum IgG antibody were investigated. The frequency of antigen for C. trachomatis was 44.4% in men with non-gonococcal urethritis and 9.1% in those with prostatitis. The serum IgG antibody was found in 59.3% of the men with non-gonococcal urethritis and in 54.5% of the men with prostatitis. There was a high change to show positive serum IgG antibody in patients with non-gonococcal urethritis of positive antigen for C. trachomatis. The variation makes the titer of serum IgG antibody a poor index of the therapy of C. trachomatis.

[Study on urinary beta-glucuronidase and alkaline phosphatase activities as indicators of CDDP renal toxicity].

Renal toxicity is the major side effect of cis-dichlorodiammine platinum (CDDP) and it develops renal tubular damage. In the present study, the acute changes of urinary beta-glucuronidase (beta-GL) and alkaline phosphatase (ALP) activities following CDDP administration as indicators of its toxicity were studied in 5 patients with urological malignant tumors. The activities were measured for 11 days continuously from the day before CDDP administration. In all cases, both urinary enzyme activities increased with CDDP administration. Increase patterns of urinary beta-GL activities were similar to those of urinary NAG, but remarkably-high values of beta-GL activities were found in cases of urothelial tumors probably because urinary beta-GL derives from the kidney (lysosomes of tubular cells) and from the epithelial cells of urinary tract. Urinary ALP activities changed corresponding well with urinary gamma-glutamyl transpeptidase (gamma-GTP). This study shows that the determination of urinary beta-GL is not a significant marker of CDDP renal toxicity, especially in cases with urological malignancies, in contrast to results for urinary brush border enzyme activities such as ALP or gamma-GTP.

[Clinical efficacy of aztreonam in patients with complicated urinary tract infections].

Aztreonam (AZT) (2 g daily) was intravenously administered for 5 to 7 days to 65 patients with complicated urinary tract infections (UTI). Ninety one organisms were isolated from these patients' urine. Among them 66 organisms were eliminated following AZT administration. The elimination rate for Gram negative organisms was 94.7% and that for Gram positive organisms was 33.3%. Thirty one organisms appeared newly by the replacement of organisms. Among them, 12 organisms were E. faecalis. The efficacy rate of AZT in single infection and in mixed infection was 55.8% and 13.7%, respectively. The overall clinical efficacy rate of AZT in the present study was 41.5%. As side effects, skin rash and itching were observed in 3 patients and slight elevations in blood chemistry were observed in 10 patients. The results indicate that AZT is an effective drug for the treatment of patients with complicated UTI, especially those caused by Gram negative organisms.

Seminal plasma transferrin concentration in normozoospermic fertile men and oligozoospermic men associated with varicocele.

Seminal plasma transferrin concentration has been reported a useful clinical marker for Sertoli cell function. In the present study, to investigate if transferrin production in the testis is decreased in oligozoospermic men associated with visible varicocele, seminal plasma transferrin concentrations in two groups -12 normozoospermic fertile men and 14 oligozoospermic varicocele patients--were measured and the values compared. Seminal plasma transferrin concentration in the oligozoospermic varicocele group was 29.9 +/- 6.8 micrograms/mL, and the concentration in the normozoospermic fertile group was 75.5 +/- 39.3 micrograms/mL. There was a significant difference between the two groups (P less than .001). The results indicate that transferrin production in the testis of oligozoospermic varicocele patients must be decreased, and also suggest that decreased transferrin production may be related to disturbed spermatogenesis in varicocele patients.

[Treatment of complicated urinary tract infections by ofloxacin].

To study the treatment effects of ofloxacin (OFLX) on the patients with complicated urinary tract infections (UTI), OFLX at a daily dose of 600 mg divided into either two or three doses per day, was administered for 14 days to 114 patients with complicated UTI. Among the 114 patients, 67 patients satisfied the criteria for clinical evaluation of complicated UTI. One hundred and one organisms were isolated from these patients' urine. Among them, 82 organisms were eliminated following OFLX administration. Twenty organisms appeared newly by the replacement of organisms. Among them, 6 organisms belonged to Candida sp. As to the overall efficacy of OFLX, an excellent response was seen in 37.3% and sum of efficacy rate was 65.7%. Side effects were observed in 3 of the 114 patients. These results indicate that OFLX is both safe and effective enough to be used for the treatment of the patients associated with complicated UTI.

[Relation of enzyme distribution in the kidney and increase pattern of urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) activities following CDDP administration].

Nephrotoxicity is the major side effect of CDDP and it develops renal tubular damage. In the present paper, we have studied acute effects of cis-dichlorodiamine platinum (CDDP, 20 mg daily for 5 days) on the renal tubule using urinary NAG and gamma-glutamyltranspeptidase (gamma-GTP) activities as indicators of the toxicity. Altogether 25 courses of chemotherapy in 15 patients who had malignant tumors were studied. Urinary enzyme activities consisting of N-acetyl-beta-D-glucosaminidase (NAG, lysosomal enzyme) and gamma-GTP (brush border enzyme) were measured for 11 days from the day before CDDP administration. In all cases, both urinary enzyme activities increased with CDDP administration. The increase of NAG activity was transient; the highest level was detected on the 5th day of chemotherapy and decreased after that. On the other hand, two peaks of gamma-GTP activity were observed in many cases, the first peak during chemotherapy and the second peak soon after the completion of CDDP administration. The differences in increase pattern of these two urinary enzyme activities, suggest that changes of brush border occur in an early stage and cellular tissue including lysosome of renal tubule is impaired afterwards.

[N-acetyl-beta-D-glucosaminidase (NAG) activity in human semen: its relation to gamma-glutamyl transpeptidase (gamma-GTP) activity in seminal plasma and reproductive tissues, and relation between seminal mucoprotein concentration and seminal NAG, and gamma-GTP activities].

N-Acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) activities in seminal plasma obtained from male infertile patients and these activities in reproductive tissues obtained from cryptorchids and patients with bladder tumors were studied. Seminal mucoprotein concentration was also measured. The mean NAG and gamma-GTP activity in seminal plasma was 2,092 +/- 794 mU/ml and 10,942 +/- 4,179 mIU/ml, respectively. The mean seminal mucoprotein concentration was 28.0 +/- 5.7 mg/ml. In seminal plasma, a significant correlation was obtained between NAG and gamma-GTP (p less than 0.001). and between gamma-GTP and mucoprotein concentration (p less than 0.05). However, there was no correlation between NAG and mucoprotein concentration. In the reproductive tissue high gamma-GTP activity was observed in the testicular tissue and in the external gland of the prostate. The activity in the epididymis was higher in the tail than in the head. High NAG activity was observed in the epididymal head and in the internal gland of the prostate. In the testicular tissue, NAG activity was low. These findings showed that in the seminal plasma NAG and gamma-GTP activities were closely related but in the reproductive tissue, these activities located in different areas.

[Prophylactic intravesical chemotherapy in bladder tumors after surgery of upper tract urothelial carcinoma].

Sixteen patients with upper tract urothelial carcinoma underwent intravesical chemotherapy usually at 2 week intervals in the first year and at 4 week intervals in the second year after nephrouretectomy. For bladder instillation 10 mg mitomycin C in 20 ml saline was used on 7 patients, 5 mg carboquone and 100 mg cytosine arabinoside in 40 ml saline on 5 patients and 30 mg adriamycin in 40 ml saline on 4 patients. Two (12.5%) of the 16 patients developed bladder tumors within 2 years after surgery, but 11 (42.3%) of the 26 patients with upper tract urothelial carcinoma who did not receive intravesical chemotherapy suffered from bladder tumor within 2 years after surgery. Prophylactic intravesical chemotherapy reduced significantly (p less than 0.1) the incidence of bladder tumor after the surgery of renal pelvic and ureteral tumors.

[Study of N-acetyl-beta-D-glucosaminidase (NAG) activity in the human semen].

NAG activity in the human semen was measured using NAG kit. Plasma NAG activity in the semen was more than 500 times higher than that of urine, while in sperm, NAG activity was low. In a frozen condition, NAG activity in semen plasma did not change for more than five weeks. NAG activity in semen plasma of male infertility associated with oligozoospermia was 1,918 +/- 829 (M +/- S.D.) mU/ml. Among the reproductive tissue, high NAG activities were observed in epididymis and prostate. Our present study suggests that NAG in semen plasma must possess some active roles related to sperm maturation and/or sperm motility or both.

[Bladder instillation of verapamil as a means of enhancing the efficacy of chemotherapy in superficial bladder carcinoma: influence of bladder instillation of verapamil on the cardiovascular system].

Although it is well known that calcium antagonists in vitro possess enhancing effects on anti-tumor drugs, their clinical use is limited on account of side effects on the cardiovascular system. In the present study, the authors attempted the instillation of Verapamil (calcium antagonist) combined with anti-tumor drugs into the bladder for the treatment of superficial bladder carcinoma. The dosage of Verapamil necessary for maintaining an effective concentration for enhancement of the anti-tumor drug was determined and the influences of bladder instillation of Verapamil on the cardiovascular system and on the bladder were studied. The results obtained were as follows: the use of 5 mg of Verapamil was able to maintain an effective concentration (10(-5) M) for enhancement of anti-tumor drugs for at least 2 h. Absorption of Verapamil from the bladder to the vascular system was minimal. No influence on the cardiovascular system or on the bladder was observed. The results of the present study encourage us to pursue the clinical use of Verapamil combined with anti-tumor drugs for the treatment of superficial bladder carcinoma.

[Urinary NAG and gamma-GTP activities as indicators of CDDP renal toxicity: effect of fosfomycin on CDDP renal toxicity].

Using urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) activities as the indicator of renal toxicity, the effect of fosfomycin (FOM) on cisdichlorodiamineplatinum (CDDP) renal toxicity was studied in 10 patients with urological malignant tumors. Regimen of chemotherapy was daily 20 mg of CDDP and 800 mg of administered by drip infusion for 5 days and 40 mg of adriamycin injected in one-push on day 1. FOM was not used at 1st cure. At 2nd cure, daily 2 g X 2 of FOM was administered for eleven days from the day before CDDP administration. Urinary NAG and gamma-GTP were measured for eleven days continuously in both 1st and 2nd cure. Effect of FOM on CDDP renal toxicity was discussed by comparison of the urinary NAG and gamma-GTP activities between 1st and 2nd cure. The results showed that urinary NAG and gamma-GTP activities following CDDP administration were deeply influenced by these activities before CDDP administration and the combined therapy of FOM had tendency to reduce CDDP renal toxicity when urinary NAG and gamma-GTP activities before CDDP administration were in the normal range.

[Encrustation and stone formation in double J ureteral stent: report of two cases].

We recently experienced two cases of encrustation and stone formation on double J ureteral stent which had been indwelt at pyeloplasty and at pyelolithotomy. In these patients, bacteriuria and pyuria had continued. Encrustation and stone formation were recognized by follow-up X-ray fairly soon after operation. Judging from our experience, encrustation and stone formation should be suspected in patients with persistent bacteriuria and/or pyuria and who have episodes of urolithiasis. To avoid encrustation and stone formation, the ureteral stent should be replaced more frequently.

[Study on urinary gamma-GTP activities as an indicator of cis-diamminedichloride platinum nephrotoxicity].

Acute change in urinary gamma-glutamyl transpeptidase (GTP) activity following cis-diamminedichloride platinum (CDDP) administration was studied in 12 patients who had malignant tumors. The activities were measured for 11 days from the day before CDDP administration and were expressed as IU/day. In all cases, the gamma-GTP activity increased with CDDP administration and decreased after completion of chemotherapy. Two peaks of gamma-GTP activity following CDDP administration were observed in many cases. In cases presenting with high gamma-GTP activity and low creatinine clearance before CDDP administration, the increase in the activity was prominent. The gamma-GTP activity before CDDP administration was significantly correlated with the gamma-GTP activity during the 10 days. This study suggests that the measurement of urinary gamma-GTP activity is important for the evaluation of CDDP nephrotoxicity, especially in cases of high gamma-GTP activity before CDDP administration.

[Acute change in urinary NAG activity following CDDP administration].

In the present paper, the acute change of urinary NAG activities following CDDP administration was studied in 8 patients with urological malignant tumors. The activities were measured for 11 days from the day before CDDP administration and were expressed as U/day. According to the NAG activity and creatinine clearance (CCr), the patients were divided into 4 types. In type I (normal NAG activity and normal CCr), the increase of the NAG activity following CDDP administration was transient. In type II (normal NAG activity and low CCr), the NAG activity increased and decreased as in type I, but in type II, the NAG activity rebounded a few days after the completion of CDDP administration. In type III (high NAG activity and normal CCr) and in type IV (high NAG activity and low CCr), the increase of the NAG activities continued longer than in type I, II; especially in type IV, the increase and the prolongation of the NAG activity was prominent. The timing of CDDP administration is considered important to avoid renal toxicity of CDDP.

Parameatal urethral cysts.

Two cases of parameatal urethral cysts in boys are reported. Both had been present from early infancy. The etiology of parameatal urethral cysts is discussed.