[Antibiotic therapy for patients with genitourinary tract infections].
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Biomedical subjects
Publications and source records attributed to Hiroshi Kiyota.
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We investigated the enhancement of the antimicrobial activities of beta-lactams against cefixime (CFIX)-resistant Neisseria gonorrhoeae in the presence of macrolides. Ten strains of CFIX-resistant N. gonorrhoeae, isolated between 2000 and 2003 from male patients with urethritis at Jikei University Affiliated Hospital and its related clinics in the Tokyo metropolitan area, were tested. The fractional inhibitory concentrations of clavulanic acid/amoxicillin (CVA/AMPC), CFIX, or cefteram (CFTM), in the presence of clarithromycin (CAM) or azithromycin (AZM), against these strains were determined. Synergism, partial synergism, or additivity was recognized between CVA/AMPC or CFTM and macrolides against nine strains. Additivity and partial synergism between CFTM and macrolides against nine and ten strains, respectively, were also recognized. On the other hand, antagonism between CFIX and macrolides was recognized. These results indicate that combination antimicrobial chemotherapy, using CFTM or CVA/AMPC with macrolides, is a possible alternative treatment for CFIX-resistant N. gonorrhoeae infections.
OBJECTIVE: To assess the significance and current status of the benign prostatic hyperplasia (BPH) impact index (BII) in the evaluation of subjective symptoms of impaired urination in so-called QOL disease, BPH. PATIENTS AND METHODS: Over the past 2 year-period, in 159 patients with the diagnosis of BPH were asked to reply to each of the international prostate symptom score (I-PSS), QOL index and BII questionnaires. The subjective symptom scores (a total of 246 points) were evaluated from the viewpoint of clinical statistics in the search for any these and to find which questions cover the BII, most. RESULTS: 1) Statistically significant but moderate correlations were observed among I-PSS total score, QOL index and BII. The correlations among Qmax, BII and QOL were very weak. 2) Out of the 11 domains in both IPSS and BII, 2 questions of BII ("bothersomeness caused by urinary problems" and "degree of worry about well-being") and 4 questions of IPSS ("residual sense," " pollakisuria," "weak urinary stream" and "nocturia") were shared as QOL indices. Patient satisfaction was affected also by the questions in the BII. 3) Of the 7 BPH symptoms assessed in IPSS, 4 symptoms ("residual sense," "pollakisuria," "weak urinary stream" and "nocturia") affected the QOL index, and 4 symptoms ("urgency on micturition," "residual sense," "nocturia" and "strain at urination") affected BII. 4) Of the 7 symptoms assessed by IPSS, different symptoms affected each of the 4 BII questions. CONCLUSION: It is needed to assess BPH symptoms not only by the IPSS and QOL index but also based on BII to provide the detailed therapeutic instructions and thorough patients consultation.
In order to establish an acceptable guideline for prevention of perioperative infection following urologic surgery, a questionnaire survey on the theory of antimicrobial prophylaxis (AMP) was conducted among urologists in Japan in February 2004. A reply was obtained from 149 urologists working for institutes located all over Japan from Hokkaido to Kyushu areas. Ninety-two percent of the urologists agreed that AMP should be administered 30 min before an incision, and 44% replied that an additional dose of AMP is required in the case of prolonged intervention. Penicillins or the 1st or 2nd generation cephems were used by 89 to 93% of the urologists in operations not including bowel segments, while 78% preferred such AMP agents in the procedures including bowel segments. AMP was terminated within 3 days in 87% for genital operations, in 70 to 76% for laparoscopic operations, in 54 to 65% for other clean or clean-contaminated operations, and in 24% for operations without the bowel segments. Especially, 58% of the urologists continued AMP for more than 5 days after operations with urinary diversion using the intestine. When compared with the previous questionnaire survey by Shinagawa et al, our survey demonstrated that standard consensus of AMP has spread widely among urologists in Japan, although the recommendations published in Europe and United States are still controversial in Japan. Thus, further well-designed clinical trials are required to establish original guidelines in Japan.
BACKGROUND: A pathway consisting of bombesin, G-protein coupling receptors (GPCRs), metalloproteases, pro-heparin-binding epidermal growth factor (proHB-EGF), and epidermal growth factor receptor (EGFR) has been reported in prostate cancer cells. The occurrence of HB-EGF shedding from proHB-EGF in this pathway, however, has not been proven directly. In addition, it is still unclear how much this pathway contributes to the migration of prostate cancer cells. In this study, we tried to directly elucidate HB-EGF shedding in this pathway and to determine its contribution to the migration of prostate cancer cells. METHODS: RT-PCR and indirect immunofluorescence staining for HB-EGF and its receptors, such as EGFR and HER4/erbB4, were performed on PC-3 cells. The influences of bombesin, anti-EGFR neutralizing monoclonal antibody, HB-EGF, and HB-EGF shedding inhibitor on the migration of PC-3 cells were studied by means of in vitro wound assays. The amount of HB-EGF shed from PC-3 cells with alkaline phosphatase-tagged HB-EGF in the presence of bombesin was determined by measuring AP activity. Immunoprecipitations and phosphotyrosine Western blotting were performed to detect EGFR transactivated by bombesin. RESULTS: PC-3 expressed HB-EGF and EGFR, but not HER4/erbB4. PC-3 migrated in the presence of bombesin, but its migration was partly inhibited by the neutralizing antibody against EGFR. PC-3 also migrated in the presence of HB-EGF, but HB-EGF shedding inhibitor partly inhibited this phenomenon. HB-EGF was shed from PC-3 cells in the presence of bombesin, and this shedding was inhibited by HB-EGF shedding inhibitor. In addition, the EGFR on PC-3 was activated in the presence of bombesin and inactivated in the presence of HB-EGF shedding inhibitor. CONCLUSIONS: These results indicated that HB-EGF shedding and the following transactivation of EGFR occurs in this pathway and that this pathway partly contributes to the migration of prostate cancer cells.
The frequency, severity, and outcome of flutamide-induced hepatic injury were prospectively evaluated in 55 patients with prostate cancer who received 125 mg of flutamide 3 times a day (daily dose: 375 mg) combined with an agonistic analogue of luteinizing hormone-releasing hormone. In addition, we examined plasma and urine concentrations of flutamide and its major metabolites 4 weeks after the beginning of flutamide therapy, and evaluated their significance in predicting flutamide-induced hepatic dysfunction. Hepatic function could be assessed in 50 patients and hepatic dysfunction during therapy was observed in 9 patients (18%); 3 patients (6%) were classified as having moderate liver dysfunction and 6 (12%) were classified as having mild liver dysfunction. The steady-state plasma levels of flutamide and its biologic active metabolite, hydroxyflutamide (OH-Flu), were not related to hepatic dysfunction. However, the concentration of another major metabolite, 4-nitro-3-(trifluoromethyl)phenylamine (FLU-1) was considerably higher in 2 patients who developed clinically significant hepatic dysfunction. These findings suggest that clinically significant hepatic dysfunction could be induced in patients with compromised flutamide metabolism, which leads to a high concentration of FLU-1. Based on results of this study, we propose that plasma FLU-1 levels are one of the predictive factors for flutamide-induced hepatic dysfunction. This hypothesis will be confirmed in a large-scale study.
The interaction between CD40 ligand (CD40L) and CD40 on antigen-presenting cells is essential for the initiation of antigen-specific T-cell responses. In order to clarify whether the expression of CD40L in tumor cells might be useful as a systemic therapy against bladder cancer, we investigated the antitumor immunity induced by CD40L in the mouse bladder cancer cell line MBT2. MBT2 was transduced by the retroviral vector expressing CD40L (MBT2-CD40L). Mouse bone marrow-derived dendritic cells cocultured with MBT2-CD40L cells produced eight times more IL-12 than those cocultured with parental MBT2 cells. In animal studies, subcutaneously inoculated MBT2-CD40L cells were rejected promptly. The vaccination of MBT2-CD40L cells induced antitumor immunity against parental tumors at a distant site. However, the antitumor effect of MBT2-CD40L inoculation was insufficient against pre-existing tumors. In the vaccination model, antibody ablation studies revealed that CD4(+) T cells were required for antitumor immunity, and tumor-specific cytotoxicity of sera was demonstrated. These data demonstrated that the antitumor immunity induced by CD40L was effective in the vaccination model and suggested that immunogene therapy using CD40L may be a new strategy of systemic therapy against bladder cancer.
Xanthogranulomatous cystitis (XC) is a rare benign chronic inflammatory disease of unknown etiology. Herein we report a case of a 70-year-old woman who presented with frequent, postmicturition pain and lower abdominal discomfort. Cystoscopy revealed a mass at the dome of the bladder near the left wall. Enhanced computed tomography (CT) demonstrated a mass with a central cavity. The patient underwent partial cystectomy because the presence of bladder neoplasm could not be ruled out. She had has no recurrence of XC 29 months after the operation. The present case of XC is the 20th to be reported in the world.
BACKGROUND: The aim of the study presented here was to stratify drug therapy for patients with benign prostatic hyperplasia (BPH) displaying various voiding symptoms. METHODS: Two different alpha1-adrenoceptor antagonists; tamsulosin hydrochloride (Tam) and naftopidil (Naf ), were administered to 96 patients with BPH for 8 weeks in a crossover study. RESULTS: With the administration of both drugs, the International Prostate Symptom Score (I-PSS) significantly decreased and the maximum urinary flow significantly increased. Whereas Naf monotherapy decreased the I-PSS for storage symptoms, Tam monotherapy decreased the I-PSS for voiding symptoms. In both the Naf-to-Tam and Tam-to-Naf groups, crossover was effective when the initial drug was judged subjectively and objectively to have been ineffective. Compliance was acceptable with both drugs. CONCLUSION: Our results show that either Naf or Tam can be used to treat patients on the basis of objective and subjective assessment of voiding symptoms. Our findings should be helpful for patient guidance and treatment of BPH.
OBJECTIVES: We performed a questionnaire survey to investigate various issues in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome by Japanese urologists and to clarify the circumstances surrounding prostatitis in Japan. METHODS: Japanese urologists (n = 1869) were surveyed by mail using a 17-item questionnaire to determine current diagnostic and treatment practices for prostatitis/chronic pelvic pain syndrome. RESULTS: Only 1.5% (11/739) of urologists diagnosed chronic prostatitis/chronic pelvic pain syndrome using the 4-glass test, while most did so using the 2-glass test (voided bladder [VB]2 and VB3, or VB2 and expressed prostatic secretion [EPS]). Approximately half (55.2%; 412/746) did not perform urine cultures to differentiate chronic bacterial prostatitis from chronic abacterial prostatitis/chronic pelvic pain syndrome. Approximately half (46%; 343/746) did not count the number of leukocytes in VB2 or VB3/EPS to differentiate chronic abacterial prostatitis from chronic pelvic pain syndrome. Although many urologists (63.8%; 459/720) thought that chronic abacterial prostatitis/chronic pelvic pain syndrome was not an infectious disease, many chose antimicrobial agents as the primary treatment. More than half (52.2%; 384/735) of all urologists felt pessimistic about dealing with chronic prostatitis/chronic pelvic pain syndrome compared to treating benign prostatic hypertrophy or prostate cancer, because of the high number of complaints by patients and their own lack of confidence in diagnosing and treating the condition. CONCLUSION: There is much confusion and frustration among Japanese urologists about chronic prostatitis/chronic pelvic pain syndrome. Further studies are needed to elucidate its etiology and pathogenesis, and to establish guidelines for its diagnosis and treatment.
Asymptomatic prostatitis is classified as category IV in NIH classification of prostatitis syndrome (1999). No report concerning this category has been present. We investigated this category histopathologically and clinically, in order to clarify the histopathological distribution and its correlation to the clinical features, in this study. Among 785 patients who were suspected prostate cancer because of their high prostatic specific antigen (PSA) values and to have a sextant prostate needle biopsy was performed between January, 1996 and December, 2000, 88 patients (11.2%) were diagnosed as NIH category IV prostatitis (asymptomatic prostatitis). We observed all pathological specimens stained with Hematoxylin-Eosine, and classified them into subtypes according to the classification criteria for prostatitis defined by True et al. (1999). We also investigated the relationship between histopathological distribution and clinical features such as PSA values, PSA density, the incidence of pyuria or bacteriuria. In the histopathological study, grade distributions were 12.5% (11/88) in mild, 71.6% (63/88) in moderate, and 15.9% (14/88) in severe. Location distributions were 2.3% (2/88) in glandular, 68.2% (60/88) in periglandular, and 29.5% (26/88) in stromal. No relationship between these subtypes and clinical features was recognized statistically. However, 7 patients (7.95%) were diagnosed as prostate cancers, later. Pyuria was found in 29.1% (23/79). Bacteriuria was present in 14.3% (11/77). Isolated bacteria were 4 strains of Enterococcus faccalis, 2 strains of each of Pseudomonas aeruginosa and Staphylococcus aureus, and one strain of each of Escherichia coli, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Staphylococcus haemolyticus, and Staphylococcus epidermidis. Gram positive rod, and Candida sp. No relationship between these subtypes and bacterial species was recognized. These results indicated that the incidence of NIII category IV prostatits was not low without correlation to any clinical features. However, we should pay attention to the presence of prostate cancer, because a small number of the patients were diagnosed as prostate cancer, later.
Papillary adenocarcinoma of the prostate, previously referred to as endometrioid carcinoma, is a variant of prostatic adenocarcinoma. Clinical and pathological evidence of involvement of the periurethral prostatic duct or verumontanum is usually required for definitive diagnosis of papillary adenocarcinoma. However, significant histologic and clinical features of papillary adenocarcinoma overlap with typical acinar carcinoma. Four cases of papillary adenocarcinoma were studied for the clinical features, histologic characteristics and immunohistochemical nature of prostatic specific antigen. In two cases, there were papillary regions, near the verumontanum, but in the other two cases, there were no papillary regions in the urethra. In two cases, acinar adenocarcinoma coexisted with papillary adenocarcinoma. All cases displayed positive immunohistochemical staining for prostatic specific antigen. In accordance with the observations of others, we suggest that papillary adenocarcinoma is one aspect of growth pattern of acinar adenocarcinoma, not a concept of a unique clinical and pathological entity.
We analyzed the chief complaints of patients with four major urogenital malignancies (renal cancer, renal pelvis and ureter cancer, bladder cancer and prostatic cancer) over the past decade (1990-1999) at the Jikei University Hospital. Over the last 10 years, a high percentage of renal cancers were detected incidentally. By contrast, prostatic cancers were more likely (10.5%) than other cancers to be detected on the basis of symptoms of metastasis. However, since 1995 more prostatic cancers are being detected with prostatic-specific antigen screening at the health checkups. Gross hematuria is the chief complaint of most patients with uroepithelial cancers (cancers of the renal pelvis, ureter and bladder cancer). Additionally, renal pelvis and ureter cancers were diagnosed with screening in a few patients in the past five years.
An X-ray diffraction experiment on ferret heart muscle was made to examine the relationship between tension and mass transfer from the thick to the thin filament associated with the interaction of cross-bridges with actin. A ferret papillary muscle was electrically stimulated for 8 s in the presence of 5 microM ryanodine to give a tetanus. At different extracellular Ca2+ concentrations (2-20 mM), a linear relationship was found between the tension and the mass transfer. It was concluded that a change in tension caused by altering the extracellular Ca2+ concentration is due to a change in the number of myosin heads bound to actin. This is in contrast to the results obtained on skinned preparations, which showed a markedly nonlinear relationship between the number of heads in the vicinity of the thin filaments and force. It was found that the tension per myosin head is similar in twitch and tetanus of cardiac muscle. Also, a similar fraction of myosin heads is recruited in tetanus of cardiac and skeletal muscles.
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We report here a case with malignant mesothelioma of testicular tunica vaginalis. An 81-year-old Japanese man with left hydrocele was referred for operation. When hydrocelectomy was performed, a thick wall of tunica vaginalis without malignancy was observed. Seven months after hydrocelectomy, a hard irregular mass was noticed in the left scrotum, therefore inguinal orchiectomy was performed. Pathologically, the mass showed severe atypia and mitosis. The diagnosis of malignant mesothelioma was made. He refused any adjuvant treatment and died 1 year later from multiple metastases to the paraaortic lymph nodes and lumbar supine.
A 46-year-old man refer to us because of hemospermia. The prostatic gland was normal in size and consistency at rectal examination. Serum prostate specific antigen was 7.04 ng/ml. Magnetic resonance imaging showed an area of low signal intensity on T2-weighted images in the left peripheral gland, possibly indicative of carcinoma. Transrectal prostate biopsy was performed after intravenous administration of piperacillin. He developed chills and fever (39 degrees C) the next morning following biopsy. He was taken unconscious into the hospital where a diagnosis of septic shock caused by Escherichia coli was made. Five days later, he died. His general condition deteriorated notwithstanding intensive treatment. Postmortem blood cultures were positive for a piperacillin resistant Escherichia coli. Histological examination of the biopsies showed a benign prostatic hyperplasia. Autopsy showed diffuse tissue damage in the heart, lung, liver and kidneys. The prostate had numerous microabscesses. Currently, transrectal prostate biopsy is considered a generally reliable procedure to detect adenocarcinoma of the prostate. Our case seems to the sixth case report of fatal complications.
A 28 year-old woman presented right upper abdominal pain. She had been pointed out her masculinization and amenorrhea. CT scan and magnetic resonance imaging showed right adrenal tumor. In the endocrinological study, the serum cortisol and testosterone was elevated. Transabdominal right adrenalectomy and nephrectomy was carried out and histopathological diagnosis was adrenocortical carcinoma. The masculine symptom had disappeared after the operation and she has been without recurrence for five years.