Clinical studies of cefpirome in the treatment of urinary tract infections caused by Enterococcus faecalis.
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Publications and source records attributed to J Kumazawa.
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PURPOSE: Since the delayed type hypersensitivity (DTH) response to testis antigens plays a key role in the induction and/or maintenance of experimental autoimmune orchitis (EAO), an animal model for human immunological male infertility or aspermatogenesis, we have investigated the immunosuppressive effect of cyclosporin A (CsA) on the DTH response to autologous testicular cells (TC). MATERIALS AND METHODS: A DTH response to autologous TC was induced in C3H/HeN mice by bilateral testicular injury (trauma). CsA was administered intraperitoneally for 10 consecutive days before and after injury. A DTH response was assessed by measuring delayed footpad reaction (DFR) to autologous TC 9 days after injury. RESULTS: When the mice were traumatized alone, 10 mg./kg. or more of CsA suppressed the DTH response to autologous TC significantly. In mice traumatized with 100 mg./kg. of cyclophosphamide (CY)-pretreatment, 30 mg./kg. or more of CsA was needed to suppress the DTH response. In mice traumatized with 200 mg./kg. of CY-pretreatment, 50 mg./kg. of CsA was needed to suppress the autoimmune response. CONCLUSIONS: The DTH response to autologous TC was suppressed significantly by administration of CsA in a dose-dependent manner. We have also shown the direct suppressive effect of CsA on effector cells for DTH by means of local passive transfer of DTH. Administration of CsA had no augmenting or suppressive effect on suppressor cells for DTH. CsA might be a significant drug for the immunosuppression of EAO and possibly for immunological male infertility.
BACKGROUND: Until recently, epidemiologic studies of sexually transmitted diseases (STDs), including human immunodeficiency virus type-1 (HIV-1) infection, among Japanese female commercial sex workers and their patterns of condom use have been rare. We investigated trends in STDs among female commercial sex workers and their condom use patterns in Fukuoka, Japan, from 1990 through 1995. METHODS: The study group consisted of 1218 female commercial sex workers who attended an STD clinic to undergo screening for major STDs including chlamydial infection, gonorrhea and HIV-1 infection from 1990 through 1995. Endocervical smear specimens were taken from the women to detect Chlamydia trachomatis and Neisseria gonorrhoeae, and blood samples were obtained for the serologic diagnosis of HIV-1. Also, the commercial sex workers were interviewed concerning their condom use patterns. RESULTS: The annual infection and detection rates of C. trachomatis declined significantly from 58.1% in 1990 to 46.2% in 1995 and from 16.3% in 1990 to 10.0% in 1995, respectively, while the annual infection and detection rates of N. gonorrhoeae also declined significantly from 13.2% in 1990 to 3.5% in 1995 and from 1.5% in 1990 to 0.4% in 1995, respectively. None were found to be seropositive for HIV-1 during the 6-year period. The proportion of commercial sex workers using condoms significantly increased during 1992-1993 and 1994-1995 periods, as compared with the 1990-1991 period. CONCLUSION: Reductions in the prevalence of major STDs among female commercial sex workers may be related to an increase in the frequency of condom use.
BACKGROUND: In addition to its role in calcium and phosphorus metabolism, calcitriol (1,25-dihydroxyvitamin D3; 1,25-D3) demonstrates multiple effects on cell proliferation/differentiation by expressing major histocompatibility complex (MHC) antigens and intercellular adhesion molecule-1 (ICAM-1). It has recently been reported that 1,25-D3 inhibits the growth of prostatic cancer (PCa) cells. In this study we examined the effect of 1,25-D3 on both the growth and expression of HLA-ABC, HLA-DR and ICAM-1 antigens in PCa cells. METHODS: Four human PCa cell lines (PC-3, PPC-1, ALVA-41 and ALVA-101) were examined. The cell numbers were enumerated, and the effects of interferon-y (IFN-gamma) and 1,25-D3 on the expression of HLA-ABC, HLA-DR and ICAM-1 were quantitated by flow cytometry. RESULTS: A dose-dependent antiproliferative effect of 1,25-D3 was found in all PCa cells lines except ALVA-41.1,25-D3 was approximately 10 times as potent as its analogue 24,25-dihydroxyvitamin D3 in inhibiting the growth of PC-3 cells. Also, the relative inhibitory ability of these compounds paralleled the strength of their binding affinities for the 1,25-D3 receptor, indicating that the antiproliferative effect may require a receptor-ligand interaction. HLA-ABC was expressed in PC-3, ALVA-41 and ALVA-101, but not in PPC-1 cells, while HLA-DR was not expressed on any of the tested cells. IFN-gammacould enhance or induce HLA-ABC but not HLA-DR expression in the tested cells. ICAM-1 was expressed in all cells and slightly upregulated by IFN-gamma. CONCLUSION: In this study 1,25-D3 had an antiproliferative effect on 3 of the 4 examined PCa cell lines.
Forty-two men with gonococcal urethritis were treated with an oral dosage of 200 mg of pazufloxacin, a new fluoroquinolone, three times daily for 3 days. Only 28 of the 42 men (66.7%) had negative culture results for Neisseria gonorrhoeae during follow-up. Of the 42 isolates, 41 could be recultured for antibiotic susceptibility testing and DNA sequencing. In 26 of the 41 isolates (63.4%), GyrA mutations with or without ParC mutations were identified. Among the 26 isolates, 23 contained a single GyrA mutation, 1 contained two GyrA mutations, and 2 contained three mutations including double GyrA and single ParC mutations. A single Ser-91-to-Phe mutation, which was detected in 14 of the 26 isolates, was the most common GyrA mutation, followed by an Ala-75 to Ser mutation and an Asp-95 to Asn or Gly mutation in GyrA. All three isolates with two or three mutations contained the Ser-91-to-Phe GyrA mutation. Eleven of the 14 isolates with the single Ser-91-to-Phe mutation within GyrA and all 3 isolates with two or three mutations persisted after pazufloxacin treatment. On the other hand, all 15 wild-type and 9 mutant isolates with a substitution at codon Ala-75 or Asp-95 were eradicated. The mean MIC of pazufloxacin for mutants with the single Ser-91-to-Phe mutation in GyrA was 66-fold higher than that for the wild type. The results obtained in this study suggest that a high prevalence of fluoroquinolone-resistant gonococcal isolates with the Ser-91-to-Phe mutation in GyrA reduced the efficacy of pazufloxacin as treatment for gonococcal urethritis.
BACKGROUND AND OBJECTIVES: Gonococcal fluoroquinolone resistance is now a significant problem in Japan. We generated gonococcal mutants resistant to norfloxacin in vitro from norfloxacin sensitive isolates and analysed the contribution of three known mechanisms of quinolone resistance in Neisseria gonorrhoeae. MATERIALS AND METHODS: Three clinical isolates of N gonorrhoeae susceptible to norfloxacin were exposed to increasing concentrations of norfloxacin. To identify mutations in the gyrA and parC genes of the gonococcal mutants, the quinolone resistance determining regions of the gyrA and parC genes were polymerase chain reaction (PCR) amplified and the PCR products were directly sequenced. Norfloxacin accumulation in the gonococcal cells was also measured. RESULTS: The MICs of norfloxacin for three variants containing a single GyrA mutation were 16-fold higher than that for their parent isolates. A variant showing reduced norfloxacin accumulation in the cells, without mutations in the GyrA or ParC proteins, was also less sensitive to norfloxacin, with a 16-fold increase in the MIC, compared with the parent strain. The MIC of norfloxacin for a variant which contained a single GyrA mutation with reduced norfloxacin accumulation in the cells was 128-fold higher than for the parent strain. A variant containing mutations in both GyrA and ParC proteins with reduced accumulation of norfloxacin in the cells showed a 256-fold increase in the norfloxacin MIC compared with the parent strain. There was no variant containing a ParC mutation without the simultaneous presence of a GyrA mutation. CONCLUSIONS: The results from this study suggest that not only a mutation in the gyrA gene but also reduced drug accumulation in cells contributes to the development of fluoroquinolone a mutation in the gyrA gene contributes to a high level of fluoroquinolone resistance in gonococci with decreases in accumulation in cells having an additional but lesser effect.
OBJECTIVE: To evaluate the performance of a new improved enzyme immunoassay (EIA) kit for the detection of Chlamydia trachomatis in vaginal swab and endocervical swab specimens from female commercial sex workers, in comparison with a conventional EIA test and a polymerase chain reaction (PCR) assay. METHODS: A high risk group of 163 female commercial sex workers who visited a sexually transmitted disease (STD) clinic in order to undergo screening for major STDs, including chlamydial infection, were enrolled. A total of four swab specimens, including two vaginal and two endocervical specimens, were collected from each woman by a clinician. To identify C trachomatis, a new improved EIA kit (IDEIA PCE), a conventional EIA kit (IDEIA), and PCR assay (Amplicor) were used. Discrepancies in the results were resolved using supplementary PCR assay. A female patient was considered to be infected with C trachomatis if the IDEIA PCE test and PCR test for both sample sites (endocervical and vaginal) gave positive results. Following resolution of these discrepancies, relative sensitivity and specificity, confidence intervals, and predictive values for each type of specimen by each assay were calculated. RESULTS: Of the 163 women tested, 35 (21.5%) were shown to be infected with C trachomatis. The relative sensitivities in vaginal swab specimens were 88.8%, 68.6%, and 91.4% using IDEIA PCE, IDEIA, and PCR, respectively. The relative specificities in vaginal swab specimens were 99.2%, 99.2%, and 100%, respectively. The relative sensitivities in endocervical swab specimens were 85.7%, 77.1%, and 91.4% with IDEIA PCE, IDEIA, and PCR, respectively. The relative specificities in endocervical swab specimens were all 100%. CONCLUSIONS: The results obtained in this study suggest that the sensitivity and specificity of IDEIA PCE test on vaginal swab and endocervical swab specimens were similar to those of PCR assay on the two types of specimen. It is concluded that IDEIA PCE test on vaginal swab specimens is an acceptable, sensitive, and less invasive approach for the detection of C trachomatis in commercial sex workers with a high prevalence of C trachomatis infection.
In the urine, the function of polymorphonuclear leukocytes (PMNs) is thought to be impaired because of the high osmolality and low pH along with a high concentration of inorganic salts. We investigated the effect of the properties of urine and its components on the chemiluminescence (CL) response of PMNs. This was helped by using an artificial urine. The CL response was measured by automatic luminometer following stimulation of phorbol myristate acetate. We found the CL response of PMNs to be significantly suppressed at a pH of 6 or 5, but not suppressed at a pH of 7 or 8. The CL response was significantly reduced when the osmolality was increased to 580 or 800 mOsm/kg H2O by the addition of urea as compared to the response in the standard artificial urine at an osmolality of 425 mOsm/kg H2O. A change in the osmolality by the addition of mannitol only minimally influenced the CL responses. In addition, the CL response was significantly impaired by both low and high concentrations of sodium at 12 and 300 mEq/L as compared to 77.5 mEq/L in the standard artificial urine. Potassium significantly reduced the CL response in a concentration-dependent manner in the range of from 4 to 31 mEq/L as compared to 52.3 mEq/L in the standard artificial urine. A high concentration of calcium at 8.1 or 9.9 mg/dL reduced CL response as compared to 3.9 mg/dL, whereas CL response was not reduced by the change in the concentration of magnesium. A high concentration of creatinine significantly reduced the CL response as compared to the standard artificial urine. We conclude that the function of PMNs in urine is reduced mainly by urine pH, concentration of urea, sodium, potassium, and creatinine. We suggest that reversal of these change in urine may restore functions of PMNs to clear bacteria in patients with urinary tract infections.
BACKGROUND: To determine what factors contribute to and change BMD in dialysis patients. METHODS: Bone parameters, namely, osteosono-assessment index (calculated by speed of sound and transmission index) were measured at calcaneus bone by ultrasonic bone absorptiometry with an Aloka Acoustic Osteoscreener (Model AOS-100). Seventy two patients were 62. 8 +/- 10.5 years of age (mean +/- SD) (range 36-81) and 70.8% were males; the patients had received dialytic therapy for 52.7 +/- 41.7 months (range 2-205). The effects of sex, age, height, weight, postmenoposal years, dialysis duration, various blood parameters, oral phosphorus binding agent (CaCO3 dosage) and oral vitamin D3 treatment (D3 dosage) on BMD were assessed statistically. RESULT: BMD in male patients were significantly higher than those in female patients (Mann-Whitney test, p < 0.01). BMD showed significant correlations with age (Spearman's correlation coefficient r = -0.384, p < 0.01), height (r = 0.479, p < 0.00001), postmenoposal years (r = -0.692, p < 0.05), dialysis duration (r = 0.250, p < 0.01), blood Ca level (r = 0.292, p < 0.05) and CaCO3 dosage, postmenoposal years and dialysis duration were the variables that significantly correlated with the BMD (multiple correlation coefficient = 0.646).
BACKGROUND: The ideal urological management for the patients with cervical spinal cord injury (CSCI) is to obtain catheter free urination and to prevent urinary tract complications. We have evaluated cases that had undergone transurethral anterior sphincterotomy from the view-point of the operative indications and the efficacy. METHODS: We carried out sphincterotomy 166 times on 133 male patients with CSCI in our Center. Before the operations were performed, all patients suffered from urinary incontinence, and they were unable to catheterize themselves for low level activity of daily life. Before and after the operation, their detrusor functions with sphincter reactions were assessed by urodynamic study. In principle we have followed up these cases by cystogram combined with cystometry, cystogram and excretory-pyelography or abdominal ultrasonography. RESULTS: In post-operative evaluations, more than 80% of cases attained hypotonic detrusor contractions and residual urine was significantly decreased. In long term follow-up, 96% of patients had obtained catheter free urination and about 85% of patients had no urinary tract complications, such as bladder deformity, vesicoureteral reflux, or hydronephrosis, with the exception of common unavoidable urinary infections. About 20% of cases had to be re-operated upon, and some cases showed hypertonic detrusor contractions or detrusor-sphincter-dyssynnergia during follow-up. CONCLUSION: The operative indications of sphincterotomy should be decided when the CSCI patients is unable to perform self-catheterization, and when due to the dysfunction of the urethral sphincter, these patients suffered from voiding difficulties or autonomic dysreflexia, or when the urinary tract complications might occur. In the majority of cases the aims of the sphincterotomy were achieved but some cases underwent another operation or had recurrent dysfunction of the urethral sphincter, indicating the need for careful follow-up.
PURPOSE: At partial nephrectomy there is a risk of excessive blood loss, which necessitates transfusion and also results in renal function deterioration when a vascular clamp is used. We evaluated the usefulness of a microwave tissue coagulator for partial nephrectomy for renal cell carcinoma. MATERIALS AND METHODS: Partial nephrectomy was performed without renal pedicle clamping using a microwave tissue coagulator in 4 patients with a small kidney tumor. RESULTS: In 3 of the 4 patients partial nephrectomy was successful using a microwave tissue coagulator without renal pedicle clamping. Mean operative time and blood loss were 203 minutes and 153 ml., respectively, and there were no significant complications. In the remaining case partial kidney resection was also performed without any complications. However, nephrectomy was required due to possible incomplete tumor resection. CONCLUSIONS: Partial nephrectomy using a microwave tissue coagulator can be safe and successful without renal pedicle clamping. However, the insertion line of the microwave electrode must be carefully determined for resection to be curative and safe, just as when making the cut line for conventional partial nephrectomy or tumor enucleation.
Three newly synthesized imidazothiazole derivatives (N276-12, N276-14, N276-17) were examined regarding their ability and mechanism as a chemosensitizing agent against multidrug resistance 1 (MDR1)-mediated and multidrug resistance-associated protein (MRP)-mediated MDR. All three N276 compounds almost completely reversed the acquired resistance to vincristine (VCR), vinblastine (VBL), and doxorubicin (DXR) in MDR1-overexpressing human cancer cell lines (KB/VJ300 and T24/VCR). Their reversal effect against acquired resistance to VCR, DXR, and etoposide (VP16) was partial but clearly observed in the cell line expressing MRP (KB/VP4). All three N276 compounds enhanced the intracellular accumulation of [3H]VCR in MDR1-overexpressing KB/VJ300 cells through the inhibition of the increased efflux of the drug. They (100 microM) almost completely inhibited the photoaffinity labeling of P-glycoprotein encoded by the MDR1 gene. All the N276 compounds also remarkably enhanced the sensitivity to VBL and DXR in both MDR1- and MRP-overexpressing renal cell carcinoma (RCC) cell line (NKK1), whereas they showed no potentiation of these anticancer agents in an RCC cell line (KPK1) expressing neither MDR1 nor MRP. The combination chemotherapy of VCR or VP16 with N276-12 significantly increased the life span of mice inoculated i.p. or i.v. with drug-resistant P388/VCR cells without any significant side effects, whereas chemotherapy with the anticancer agent alone did not increase the life span at all. These results suggest that these newly synthesized imidazothiazole derivatives can be a useful chemosensitizing agent against not only MDR1- but also MRP-mediated MDR.
Polymorphonuclear leukocytes (PMNs) are one of the most important components of the defence mechanisms against bacterial infection. The functions of PMNs are believed to be impaired in patients during the perioperative period. Bactericidal function of PMNs was investigated together with the luminol-dependent chemiluminescence (CL) reaction of whole blood in 23 patients, 12 undergoing open surgery and 11 undergoing endoscopic surgery. Blood samples were collected one day before surgery (day -1) and 2 hours (day 0), 24 hours (day 1) and 7 days (day 7) after surgery. Counts of whole white blood cells (WBCs), PMNs and lymphocytes were not different between the two surgery groups. CL responses in the open surgery group were increased on days 0, 1 and 7. In the endoscopic surgery group, CL response was increased on day 1, but not on day 0 or day 7. These results suggest that the PMN function during the perioperative period was not impaired, but increased just after surgery, mainly due to an increasing number of WBC caused by the surgical intervention.
BACKGROUND: Radical nephrectomy is the standard therapy for low-stage renal cell carcinoma. However, recurrence sometimes develops even in patients who are considered to have undergone a curative resection of the primary tumor. The purpose of this study was to evaluate the usefulness of UFT (a 1:4 mixture of tegafur and uracil) adjuvant and the risk factors for recurrence in renal cell carcinoma. METHODS: A prospective randomized trial was conducted to compare the use of long-term oral UFT adjuvant with nonadjuvant therapy after a radical nephrectomy for Robson stage I or II renal cell carcinoma. A multivariate analysis was also performed to estimate the risk factors for recurrence. RESULTS: A total of 71 patients were entered into this study, and 66 were evaluable (33 for each group). There was no significant difference in patient characteristics between the 2 groups. The nonrecurrence rate at 5 years after a radical nephrectomy was 80.5% and 77.1% in the UFT adjuvant group and the nonadjuvant group, respectively, with a median follow-up of 112.9 months; the difference was not significant. The toxicity of UFT was generally mild and tolerable. The tumor grade was found to be an important factor influencing recurrence. CONCLUSION: UFT cannot be universally recommended as an adjuvant therapy for radical nephrectomy in all patients with low-stage renal cell carcinoma.
BACKGROUND: The prevalence of lower urinary tract symptoms was determined by survey as an initial step in estimating the significance of benign prostatic hyperplasia (BPH) in Asia and Australia. METHODS: The symptom index (0 to 35) and quality-of-life (QOL) index (0 to 6) of the international prostate symptom score were measured in 7588 men in 9 Asian countries and 146 men in Australia. RESULTS: The percentages of Asian men considered to be symptomatic (symptom index > or = 8) were 18%, 29%, 40%, and 56% in the age groups of 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, respectively. For Australian men, these figures were 36%, 33%, and 37% in the 50 to 59, 60 to 69, and 70 to 79 year age groups, respectively. CONCLUSIONS: Our estimates indicate that the prevalences of symptomatic men in Asia and Australia are similar to or greater than those in Europe and America, and suggest BPH is similarly common in these areas.
BACKGROUND: The postoperative intravesical instillation of doxorubicin (ADM) has a preventative effect on recurrence after a transurethral resection (TUR) of superficial bladder cancer. However, the significance of preoperative ADM instillation remains unclear. Although the oral administration of 5-fluorouracil (5-FU) has been observed to show some clinical response against bladder cancer, its preventative effect on the recurrence of superficial bladder cancer after TUR is unknown. METHODS: Patients were randomized into 4 groups. All 4 groups received postoperative ADM instillation. In addition, patients in groups C and D received preoperative ADM instillation, whereas patients in groups B and D additionally received oral 5-FU postoperatively. The nonrecurrence rate and side effects were both compared among the 4 groups. RESULTS: Of the 282 patients registered, 200 were evaluable, with a median follow-up period of 21.4 months. There were no significant differences in the characteristics of the patients among the 4 groups. Group C (pre- and postoperative ADM) showed a significantly longer disease-free interval than group A (postoperative ADM alone). However, there was no significant difference in the disease-free interval between groups A and B (postoperative ADM plus 5-FU), or between groups C and D (pre- and postoperative ADM plus 5-FU). Bladder irritation symptoms were the most frequently noted side effect encountered in all groups, but the severity was generally mild. CONCLUSIONS: Preoperative ADM instillation was found to prevent recurrence to a greater extent than the usual postoperative instillation alone, whereas oral 5-FU was found to have no additional beneficial effect on the disease-free interval in patients with superficial bladder cancer.
Most Escherichia coli isolates from patients with pyelonephritis possess both pap (mannose-resistant) pili and type 1 (mannose-sensitive) pili. In the experimental pyelonephritis model of rats, the mannose-sensitive-piliated strain caused severe renal scarring, whereas the mannose-resistant or nonpiliated strain did not. Type 1 pili consist of several subunits; one major subunit and other minor subunits. One of the minor subunits, adhesin, is responsible for mannose-sensitive adhesion to eukaryotic cells. The role of adhesin was examined in scar formation after infection with a newly constructed adhesin-deficient mutant which has pilus structure but cannot agglutinate guinea pig erythrocytes. A mutant plasmid, pYMZ84, containing a deletion in the adhesin gene of type 1 pili, failed to agglutinate guinea pig erythrocytes even though the bacteria expressed pili morphologically indistinguishable from those produced by plasmid pSH2, carrying the intact genes for the type 1 pili. E. coli harboring pYMZ84 caused negligible or minimal renal scarring, whereas E. coli harboring pSH2 caused severe renal scarring in rats. These data suggest that the mannose-sensitive adhesin of type 1 pili stimulates renal scarring.
The incidence of catheter-associated urinary tract infections (UTIs) becomes higher with prolongation of the indwelling period of a catheter. As to the entry of bacteria, ascending UTIs have now attracted attention. In the present study. the metal area was examined bacteriologically and the possibility to use antiseptics for blocking the route of developing infections was investigated. The subjects included 72 patients with an indwelling, urethral catheter inserted post-operatively. These patients were divided into three groups treated with once or twice daily application of povidone-iodine or once daily application of povidone-iodine cream. In these groups, the relation between changes in isolation of bacteria from the meatal area and the incidence of UTI was evaluated. It was found that reduction in bacterial count by antisepsis is effective to prevent ascending UTIs. Moreover, once daily application of povidone-iodine was proven to be effective in male patients. The effective antisepsis in females was twice daily application of povidone-iodine.