ishikawa kiyohito

We report the case of a 52-year-old man who underwent a renal transplantation and subsequently developed extrapulmonary tuberculosis. The immunosuppressive agent was intravenously administered continuously together with antituberculosis drugs. The tuberculosis improved and renal function has been well preserved for more than 3 years post transplantation.

The susceptibility of 10 antimicrobials against P. aeruginosa isolated from complicated UTI during 1992-1995 was determined, and the yearly trend was examinated. The drug tested included 3 cephems (ceftazidime [CAZ], cefpirome [CPR], cefclidin [CFCL]), 1 monobactam (aztreonam [AZT]), 2 carbapenem (imipenem/cilastatin [IPM/CS], biapenem [BIPM]), 2 aminoglycosides (netilmicin [NTL], gentamicin [GM]) and 2 new quinolones (ofloxacin [OFLX], ciprofloxacin [CPFX]). A total number of isolates of which MIC were determined was 77 in 1992/1993 and 70 in 1994/1995. MIC₅₀/MIC₉₀ (p&mu;g/ml) on the isolates were as follows (1992/1993 1994/1995); 3.13/100 12.5/50 in CAZ, 12.5/100 12.5/100 in CPR, 3.13/25 1.56/25 in CFCL, 6.25/50 12.5/100 in AZT, 6.25/25 3.13/25 in IPM/CS, 1.56/6.25 0.78/50 in BIPM, 12.5/100 6.25/100 in NTL, 6.25/50 6.25/100< in GM, 25.100< 25/100< in OFLX, 6.25/100 6.25/100< in CPFX. When the susceptibility of the yearly trend is compared, no significant changes were detected among the drugs tested expect the decrease of susceptibility on CAZ, AZT and increase of it on IPM/CS. From the data obtained, against complicated UTI infected by P.aerugunosa, CFCL, IPM/CS and BIPM are considered to drugs of first choice in the treatment.

A clinical study was performed in 13 cases of refractory Enterococcus faecalis pyelonephritis that were detected in the Department of Urology, Hiratsuka Municipal Hospital, from April 1975 to March 1995. The characteristic features were that pyelonephritis was commonly seen in females, and clinical symptoms (low-grade intermittent fever, low back pain, general malaise, etc.) were continuously refractory. Bacteriuria or polymicrobial infections were often found, and bacterial count was often as high as 10(2)-10(4)/ml. Nevertheless we considered that E. faecalis caused of refractory pyelonephritis must not have week adherence and pathogenesis to the kidney, owing to the clinical symptoms and the basic subjects. Furthermore this infection was difficult to cure completely with antimicrobials having activity against E. faecalis, and long-term treatment was needed. Therefore, we recommend that treatment for refractory E. faecalis pyelonephritis be carefully selected according to clinical symptoms and the bacterial density of this strain.

We performed basic and clinical studies of NM441, a new quinolone antibiotic, in chronic bacterial prostatitis, and the following results were obtained.<BR>1. Basic study<BR>1) Human prostatic tissue concentrations<BR>Concentrations in the prostatic tissue (Mean) were 1.72, 1.20, 1.25, 1.29, 1.17, 0.52 and 0.38&mu;g/g, and the serum concentrations (Mean) were 1.42, 0.40, 0.28, 0.42, 0.36, 0.19 and 0.06&mu;g/ml at 1.5, 2, 2.5, 4, 6, 8 and 24h after 200mg of NM441 administration, respectively. The ratios of the concentrations of prostatic tissue and serum were 0.71 to 13.0.<BR>2) Human prostatic fluid concentrations<BR>Concentrations in the prostatic fluid were<0.01 to 0.44&mu;g/ml at lh after 200mg of NM441 administration, and mean concentrations were 0.05, 0.02 and 0.14&mu;g/ml at 1.5, 2 and 4h after administration, respectively. The serum concentrations (Mean) were 0.50, 0.73, 0.80 and 0.28&mu;g/ml at 1, 1.5, 2, and 4h after administration, respectively. The ratios of the concentrations of prostatic fluid and serum were 0.02 to 1.62.<BR>2. Clinical study<BR>NM441 was orally administered to 22 patients with chronic bacterial prostatitis at a dose of 200mg twice a day for 10-22 days (Mean: 14.3 days). The clinical efficacy rate was 76.5% in 17 patients evaluable according to the criteria of the Japanese UTI Committee.<BR>Side effects were observed in a total of 2 cases; stomach discomfort and heartburn in 1, and oral cavity discomfort in 1, but all were mild and the treatment was continued. An abnormal laboratory finding was observed eosinophilia in 1 case, but this case recovered at 8 days after the termination of administration.

NM441, a new oral quinolone antibiotic, was administered to 74 patients with urinary tract infections at a daily dose of 100-600mg for 3-7 days. The patients evaluable according to the criteria of the Japanese UTI Committee were 60 cases, and the clinical efficacy rates were 100%(11/11) in acute uncomplicated cystitis and 63.3%(31/49) in complicated urinary tract infections. Side effects were observed in a total of 5 cases; headache and nausea in 1 and digestive symptoms in 4. Abnormal laboratory findings were observed in a total of 3 cases; an elevation of GPT in 1, elevations of BUN and serum creatinine in 1 and an elevation of serum creatinine in 1.

Balofloxacin (BLFX), one of the newer quinolones, was investigated for its in vitro activity, diffusion into prostatic fluid (PF) and clinical efficacy in the treatment of urinary tract infection (UTI). The results obtained were as follows.<BR>1. In vitro activity: Against 80 strains of Enterococcus faecalis isolated from UTI, the MIC of BLFX ranged from 0.20-25&mu;g/ml, and the MIC₅₀ and MIC₉₀ were 0.78&mu;g/ml and 12.5&mu;g/ml, respectively, roughly comparable to sparfloxacin. The drug appeared to be superior to other reference drugs such as norfloxacin, ofloxacin and ciprofloxacin. However, BLFX was less potent against 50 strains of Pseudomonas aeruginosa, for which the MIC₅₀ and MIC₉₀ were as much as 25&mu;g/ml and >100&mu;g/ml.<BR>2. Diffusion into PF: The concentration in PF at 1 hr after administration of 200 mg reached 0.01-0.94&mu;g/ml, with an average of 0.35&mu;g/ml (n=7), while that in serum, ranged from 0.06-1.96&mu;g/ml, with an average of 0.79&mu;g/ml. The ratio for PF/serum was 0.35.<BR>3. Clinical assessment: A total of 38 UTI patients were given BLFX at doses of 100-200 mg, once or twice a day for 3-14 days. The patients included 14 cases of acute uncomplicated UTI, 23 cases of chronic complicated UTI and one case of acute prostatitis. According to the evaluation by the doctor (s) in charge, 30 of 38 evaluable cases, 78.9%, were assessed as effective (excellent/good), while according to the Japanese UTI criteria, 28 of 34, 82.4%(excellent/moderate), were determined to be effective. The bacteriological response rate was 13 of 14, 92.9%, in uncomplicated UTI, and 17 of 23, 73.9%, in complicataed UTI.<BR>As for the safety profile, 3 of 39 patients treated with BLFX experienced adverse reactions (CNS) disturbance/GI disorder 1, CNS 1, GI disorder 1, however they were mild and transient, and disappeared after the completion of therapy without any treatment. No clinical abnormal values were detected in laboratory tests in any of the patients.

Cefluprenam (CFLP), a new injectable cephem antibiotic, was administered in the treatment of 16 cases with chronic complicated UTI and 1 case with acute prostatitis. The results obtained were as follows. Seventeen patients who received the drug were given at a dose of 0.5g or 1.0g, twice a day by drip infusion for 5 days. In complicated UTI, 15 patients out of 16 were evaluable by the Japanese UTI criteria, and its assessment was excellent or moderate in all cases treated (efficacy rate: 100%). In 1 case of acute prostatitis the effectiveness was fair. Response against clinical isolates, 25 strains out of 26, that included 16 of gram negative bacilli, 10 of gram positive cocci, were eradicated after treatment. A great potent in vitro activity on such strains as Escherichia coli, Morganella morganii, Proteus mirabilis, was proven as much as &le;0.05 &mu;g/ml of MIC values. So far the clincal data obtained, the relationship between the in vitro study and the clinical one was considered to be detected. In the safety profile, nothing was observed for adverse drug reaction. In laboratory values, in 2 cases, mild transient elevations of S-GOT, S-GPT/S-GOT, SGPT, &gamma;-GTP were noted. Conclusively, CFLP showed a useful strategy for complicated UTI, even though with stubborn UTI caused by Pseudomonas aeruginosa, Enterococcus faecalis. As for safety, no significant differences were observed, compared to the conventional compounds.

Pazufloxacin (PZFX), a new family of oral newer quinolones, was tested for the in vitro activity on several strains of Pseudomonas aeruginosa isolated from UTI. For clinical evaluation, the drug was administered in the treatment of UTI, prostatitis. The results obtained were shown in the following<BR>1) In vitro activity on several clinical isolates of P. aeruginosa: The MIC values on the strains tested, varied according to the pH values of medium. When comparing with other conventional drugs, the in vitroactivity of PZFX was less influenced by the culture medium than the other control drugs. The MIC values of PZFX had a tendency to more active in acid media than in alkaline media.<BR>2) Penetration into human prostatic fluid after intake of 200 mg of PZFX: Average concentration (&mu;g/ml) of prostatic fluid (PF) was 0.18 &plusmn; 0.11 (n=4) at 1 hour, and it was 0.20 (n=2) at 2 hours. The ratio between PF/serum was 0.12&plusmn; 0.11 (1h), 0.26 (2 h) respectively.<BR>3) Patients with genitourinary tract infection were treated with oral administration of PZFX 50-200 mg b.i.d. or t.i.d. after meal for 3-14 days. According to the criteria proposed by the Japanese UTI Committee, the overall clinical efficacy of PZFX was 100%(14/14) in uncomplicated UTI, 90%(18/20) in complicated urinary tract infection and 3/3 in prostatitis.<BR>4) For safety, mild loose stool was observed in one patient, during the course of therapy. Laboratory abnormal values were detected for slight elevation of GPT in one case, also that of GOT, GPT and AlP in the other case.

Two cases of retroperitoneal leiomyosarcoma are presented. The first case was in a 67-year-old female, whose chief complaint of right upper abdominal mass and dull pain. The tumor, 13 x 12 x 8 cm in size, developing in the retroperitoneum was removed with the right kidney and vena cava. The pathological diagnosis was reported as leiomyosarcoma. The second case was in a 62-year-old male, whose complaint was left abdominal swelling, also with general fatigue. A large tumor mass, invading over all of the left flank organs, was palpable by physical examinations, from which the mass was far beyond surgical approach. Needle biopsy revealed the pathological finding of leiomyosarcoma. One month later, the patient died of cachexia. Review of the literatures for the retroperitoneal leiomyosarcoma, revealed only a few cases; 1.7%, of all leiomyosarcoma to date.

A new oral quinolone antibacterial drug, grepafloxacin (GPFX), was administered to a total of 52 patients, including 51 cases of urinary tract infections (UTI) and 1 case of chronic prostatitis, to examine its therapeutic efficacy and safety. In addition, its concentration in prostatic fluid was measured. GPFX was administered to patients with uncomplicated cystitis at a dose of 100 mg once a day for 3-5 days, and for patients with complicated UTI, the drug was given at a doses of 200-300 mg once a day or divided into 2 doses a day for 5 days.<BR>According to the criteria proposed by the Japanese UTI Committee, the efficacy rate was 100%(11/11) in uncomplicated cystitis, while it was 44.4%(12/27) in complicated UTI. In complicated UTI, the bacterial eradication rate was 10/15 (66.7%) for gram-positive cocci and 15/24 (62.5%) for gramnegative bacteria.<BR>The prostatic fluid concentration of GPFX at 1-4 hours after oral administration at doses of 200-300 mg was 0.03-0.53&mu;g/ml, with a serum ratio of 0.12-1.71. In regard to safety, subjective adverse reactions included 2 cases of GI disorder, 3 cases of CNS disorder and 1 case of allergic skin eruption. Abnormal laboratory findings included 1 case of slight elevation of sGOT, increase of neutrophils and lymphocytopenia.

We present a case of a uretero-aortic fistula assumed to be caused by an indwelling ureteral catheter.<br>A 65-year-old male who underwent cystectomy and ureterocutaneostomy with bilateral ureteral stents had been well until gross hematuria from the left catheter developed. In spite of a through radiological examination of the left kidney, no abnormal findings were noted. However, massive hemorrhage was encountered on catheter exchange, prompting us to suspect a formation of a uretero-arterial fistula. CT scan was performed again, demonstrating severe adhesion between the left ureter and the aorta at the crossing point.<br>At exploration, a fistula of about 7mm between the left ureter and anterior surface of the aorta was recognized. Left nephro-ureterectomy and closure of the aortic fistula with a rectus muscle fascia wrapping was successfully performed. His postoperative course was uneventful.<br>Because the continued increase in the utilization of ureteral catherers could cause frequent occurrence of this condition, urologists should be aware of a uretero-arterial fistula as possible serious complication of indweling ureteral catheters.

The trend of epidemiological study against MRSA stains which were isolated in 1992 and in 1993 was investigated. Number of stains tested yearly consisted of 30 isolates that were considered to play pathogenic roles for inpatients in clinical departments at our institute. In comparing with biological studies on MRSA stains and the epidemilogical surveillance of the background of the isolation, the data summerizes as followings;<BR>1) No.of MRSA stains which were producible for TSST increased from 24/30, 80% up to 30/30, 100%.<BR>2) No.of enterotoxin type harbouring bitype of B/C increased 0/30, 0% up to 12/30, 40%.<BR>3) No.of type of plasmid DNA profile increased in varying from 3 types (A, B, C) to 8 types (A-H).<BR>4) The in vitro activity of antimicrobials, as such MINO, GM, IPM, CMZ was less potent than that of the prior year, and even for VCM, ABK, the activity proved less potent in 1-2 tubes in MIC₉₀.<BR>5) No.significant hospital acquired infection was detected between the inpatients, with MRSA infection and isolates from plasmid DNA profiles.<BR>6) Since the ratio of the coincidence of plasmid DNA profiles of MRSA was only in 4 patients out of 27, 14.9 &, nosocomial infections with MRSA brought to patients have not only been considered by medical, paramedical staff, but that the infection may be caused by broad contamination at the institute.

The following results were obtained for a new oral penem antibiotic, ritipenem acoxil (RIPMAC).<BR>1. Diffusion into human prostatic fluid<BR>The concentration of ritipenem (RIPM) in the prostatic fluid at 1 hour after administration of 400 mg RIPM-AC was less than 0.08 &mu;g/ml in all of 4 human prostatic fluid specimens tested.<BR>2. Clinical study on UTI<BR>The drug was given at daily doses of 450-600 mg divided into 3 times, for a period of 3-7 days in 24 patients with UTI.<BR>According to the Japanese UTI Committee's criteria, the efficacy on 17 patients with chronic complicated urinary tract infection was excellent in 11 patients, moderate in 4 and poor in 2, thus, a response rate being 88.2%. As for side effect, stomach discomfort was found in one patient. There were no particular significant abnormal laboratory values.

FK037, a new injectable cephem antibiotic, was administered in the treatment of 13 acute bacterial prostatitis (mean age 53.5, range 30-79), and its effectiveness and safety were evaluated. The human prostatic fluid (PF) concentration of FK037 on 7 specimens 1 hour after 1 g i.v.d., was in the range of 0.87-7.47 micrograms/ml (mean +/- SD, 3.43 +/- 2.23 micrograms/ml), whereas, the serum concentration averaged 45.3 +/- 2.88 micrograms/ml, the ratio of PF/serum consequently being 0.08 +/- 0.05. In the clinical study, 1g of FK037 was administered to 13 patients by i.v.d. twice a day for 7-9 days. Bacteriological eradication on expressed prostatic secretion (EPS) was obtained for all clinical isolates which included 11 strains of Escherichia coli (MIC < or = 0.05 microgram/ml), 2 of Enterococcus faecalis, and each one of Staphylococcus aureus and Morganella morganii. Symptomatical cure was 100% in all cases. As for safety profile, no side effects were noted. In laboratory values, slight elevation of transaminase were detected in 3 cases, but they were transient and returned to normal 1-2 weeks after completion of the therapy. We conclude that FK037 is highly effective in the treatment of acute bacterial prostatitis, and is well tolerated in comparison with other relative antimicrobials.

Clinical studies were carr+ied out to assess the effect and safety of biapenem (BIPM) in urogenital field infections, and the results were as follows.<BR>In the laboratory study, the MIC₅₀ of BIPM against 77 clinical strains of Pseudornonas aeruginosa isolated from c-UTI in 1992/1993 was 1.56&mu;g/ml, which was lower for 2 tubes than imipenem.<BR>In the clinical study, thirty-nine patients, including 28 cases of chronic complicated UTI, 3 of acute uncomplicated pyelonephritis and 8 of acute bacterial prostatitis, were treated at doses of 300-1200mg a day for 2-10 days. In complicated UTI, the clinical efficacy was excellent or moderate in 19 of 21 patients (90%). For the bacteriological response, in 19 strains of 8 species of GPC, and 17 strains of 8 species of GNB, 94% of bacteria were eradicated after treatment. In uncomplicated UTI and acute bacterial prostatitis, the clinical efficacy was 100%. No side effects were observed. In abnormal laboratory findings, mild transient elevation of GPT in 3 cases and decrease of leucocytes in 1 case were observed.

FK037, a new injectable cephem antibiotic, was administered in the treatment of 14 complicated urinary tract infections.<BR>The drug was given at doses of 0.25-1.0g b. i. d. by intravenous drip infusion for 5 days. The clinical efficacy was evaluated as excellent or moderate in 11 cases out of 13, 85% by the Japanese UTI criteria. Bacteriologically, 20 strains out of 22, 91% were eradicated after the therapy. Against strains of Pseudomonas aeruginosa, the response was 1 out of 3 strains. In the safety profile, no side events or abnormal laboratory findings were caused by FK037.

For the treatment of urinary tract infections (UTI), a newly developed injectable antibiotic agent, tazobactam/piperacillin (TAZ/PIPC), was administered to 22 UTI cases (complicated: 21, uncomplicated: 1) at a dose of 2.5g/day to 5.0g/day for 5 to 6 days. The results obtained were as follows:<BR>1. Of the 22 cases, 20 cases were evaluable for clinical efficacy by the Japanese UTI criteria. Excellent or good efficacy was obtained in 85%, or 17 out of 20 cases.<BR>2. The clinical isolates obtained before treatment were 11 species of bacteria and 30 strains.After treatment, 26 strains were eradicated. Thus, the eradication rate was 86.7%.<BR>3. Among 27 strains whose &beta;-lactamase production was examined, 15 produced penicillinase and/or cephalosporinase.<BR>4. The drug showed superior antibacterial activity even against &beta;-lactamase producingstrains, as well non-producing strains, especially against Serratia marcescens, in comparison with piperacillin.<BR>5. No subjective or objective adverse reactions were observed in any treated cases. Slight elevation of GPT was observed in two cases and eosinophilia was observed in one case.

A new oral penem antibiotic, SY5555, was administered in the treatment of urinary tract infection and prostatitis. The drug was given at doses of 300-600 mg a day for 3-14 days. The clinical efficacy was evaluated by the Japanese UTI Committee criteria in 44 of 58 patients treated. The efficacy was 100% in 24 cases of acute uncomplicated cystitis, and 60%(9 of 15) in chronic complicated UTI. Among 3 cases of acute bacterial prostatitis caused by Escherichia coli, bacteriological eradication was achieved in only one case. In the safety profile, adverse events were noted in 7 cases (12.5%) including mainly digestive disorders such as diarrhea or loose stool. No abnormal values were detected except for slight elevation of &gamma;-GTP in one case.

We evaluated transurethral resection of bladder tumor (TUR) for stage T1b & T2 bladder cancers by reviewing our long-term results from 181 patients. All were followed for a minimum of 5 years or until death.<br>In 29 patients with a stage T1b tumor treated by TUR, the 5- & 10-year survival rates were 82.5&plusmn;7.1 and 73.4&plusmn;8.8. Bladders were successfully preserved in 16 patients, whereas seven patients died of cancer, all of whom experienced tumor recurrence and progression at the same site as the initial lesion (true local recurrence). Conservative treatment is supposed to be indicated for a stage T1b tumor because more than half could be treated successfully by TUR. However, considering the true local recurrence, for which incomplete resection of primary lesion seems responsible, we believe that re-TUR (a second resection of the primary lesion area) is essential to evaluate the residual tumor. Radical cystectomy should subsequently be considered after re-TUR proved residual tumor because conservative treatment no longer appears reasonable and places the patients at undue risk regarding serious disease progression.<br>As for eight patients with a stage T2 tumor treated by TUR, only one had no recurrence. The others died of recurrence of invasive tumors. In contrast, the 5- & 10-year survival rates of the patients treated by cystectomy were both 63.6&plusmn;14.5%. Based on these data, radical cystectomy should be required as initial treatment for a stage T2 tumor.