Nobuaki Honda

Pharmacokinetic–pharmacodynamic target attainment analysis of doripenem in infected patients

This study was a pharmacokinetic (PK)-pharmacodynamic (PD) target attainment analysis of doripenem. Drug concentration data in plasma (115 samples) and urine (61 samples) from 18 infected patients were concurrently analysed to develop a more accurate population PK model for doripenem. In the final PK model, creatinine clearance (CL(Cr)) was the most significant covariate: CL(r) (L/h)=0.137xCL(Cr); CL(nr) (L/h)=2.49; V(1) (L)=8.29; Q (L/h)=8.10; and V(2) (L)=9.37, where CL(r) and CL(nr) are the renal and non-renal clearances, V(1) and V(2) are the volumes of distribution of the central and peripheral compartments, and Q is the intercompartmental (central-peripheral) clearance. Based on the PK model, a Monte Carlo simulation predicted the probabilities of attaining the bactericidal exposure target (40% of the time above the minimum inhibitory concentration (MIC)) in plasma and defined the PK-PD breakpoints (the highest MIC values at which the target attainment probabilities were >or=90%). The breakpoint for 500 mg every 8h (q8h) (1-h infusion) with a CL(Cr) of 80 mL/min (1 microg/mL) corresponded to those for 250 mg q8h with a CL(Cr) of 40 mL/min and 250 mg every 12h with a CL(Cr) of 20 mL/min. Prolonging the infusion time was a more effective strategy than dose escalation to increase the breakpoint. These results provide guidance for constructing a PK-PD-based strategy for dosing guidance for tailoring doripenem regimens.

Long-term results of endoureterotomy using a holmium laser

Abstract:  The long‐term results of endoureterotomy using a holmium laser in cases of benign ureteral stricture, uretero‐pelvic junction obstruction (UPJ‐O) and ureteroenteric stricture were evaluated. Twenty procedures were carried out in 18 patients. Strictures were incised with a holmium laser using a fiber passed through the ureteroscope. Sixteen of the 20 procedures (80%) were successful at average follow‐up of 60.5 months (range, 46–74). Stricture recurred in four cases. All failures occurred within 18 months. Although stricture length was not correlated with recurrence, all failures, with the exception of a single UPJ‐O, involved middle ureteral strictures. Endoureterotomy using a holmium laser affords favorable results with respect to long‐term patency. This procedure is recommended as a satisfactory therapeutic option for the initial management of patients presenting with ureteral stricture.

Contrast-enhanced ultrasound using a time-intensity curve for the diagnosis of renal cell carcinoma.

Study Type – Diagnosis (non‐consecutive series)

THE TREATMENT WITH TRANILAST, A MAST CELL BLOCKER, FOR IDIOPATHIC OLIGOZOOSPERMIA

Although many drug treatments have been reported to theoretically improve semen parameters in male infertility, a standard method has not been established. The authors examined whether tranilast, a mast cell blocker, improves fertility and/or semen parameters in severe oligozoospermia. Seventeen patients with a sperm density of less than 10 2 10 6 sperm/mL and their fertile partners were enrolled in this study. Patients were prescribed tranilast 300 mg/day for at least 12 weeks. Semen and blood samples were collected before and after the prescription of tranilast for 12 weeks. Semen parameters, serum gonadotropins, luteinizing hormone, follicle-stimulating hormone, serum testosterone, and testicular size were evaluated. One patient complained of mild drowsiness during treatment. The sperm count was significantly increased after administration of tranilast in 7 patients (41.1%), although sperm motility was not altered. Semen volume and normal morphology were also unaltered. Three pregnancies were achieved. Endocrine profile and testicular size were unchanged. Tranilast, a mast cell blocker, is clinically useful for the treatment of severe idiopathic oligozoospermic men.

Treatment of Oligoasthenozoospermia with Tranilast, a Mast Cell Blocker, After Long-Term Administration

The authors retrospectively examined whether long-term administration of tranilast improves semen parameters in severe oligoasthenozoospermia. Fifty-two patients presenting with sperm concentration of less than 10 2 10 6 sperm/mL were enrolled. Subjects were partitioned into 3 groups as follows: patients displaying an atrophic testis with elevated (FSH) (group 1), patients exhibiting normal testicular volume with elevated FSH (group 2), and patients with normal testicular volume and normal FSH levels (group 3). Tranilast (300mg/day) was administered until pregnancy was achieved or for a period of up to 12 months. Sperm concentration was significantly increased at 3 months in 16 subjects (44%) in groups 1 and 3. In group 2, sperm concentration was increased at 12 months (5 of 16 subjects; 31%). Total sperm count was obviously elevated at 3 months in groups 1 and 2, and at 6 months in group 3. Six pregnancies were achieved via natural intercourse. Tranilast, a mast cell blocker, demonstrates a certain clinical benefit in terms of improvement of semen parameters involving severe oligoasthenozoospermia, but it does not appear to afford clinical benefit in long-term administration.

PROBABILITY OF SPERM RECOVERY IN NON-OBSTRUCTIVE AZOOSPERMIC PATIENTS PRESENTING WITH TESTES VOLUME LESS THAN 10 ml/FSH LEVEL EXCEEDING 20 mIU/ml

We evaluated the sperm recovery rate in non-obstructive azoospermia (NOA) patients presenting with bilateral testicular atrophy characterized by testes volume of less than 10 ml and FSH levels exceeding 20 mIU/ml (group NOA-1), and compared the results to those NOA cases displaying unilateral testis volume exceeding 10 ml or FSH levels less than 20 mIU/ml (group NOA-2). Sperm retrieval was conducted in 261 azoospermic patients from April 1995 to December 2002. Forty-six NOA-1 and 37 NOA-2 individuals underwent microdissection TESE or 3–4 standard biopsies. Sperm recovery was achieved in 11 (24%) and 12 (32%) cases in NOA-1 and NOA-2, respectively. All couples received ICSI. Four clinical pregnancies (36.3%) in NOA-1 and two (17%) in NOA-2 resulted. Five subsequent healthy deliveries were obtained. NOA patients presenting with bilateral severe atrophic testes volume and obviously elevated FSH levels exhibited approximately 24% probability of sperm recovery. On the other hand, NOA characterized by testicular atrophy or elevated FSH levels displayed probability of approximately 32%. Differences in sperm recovery were not evident between NOA-1 and NOA-2. No successful pre-operative predictors of sperm recovery were identified.

Retrograde ureteroscopic endopyelotomy using the holmium:YAG laser

Abstract Background : We report our experience of retrograde ureteroscopic endopyelotomy using the holmium laser for ureteropelvic junction (UPJ) obstruction not associated with upper tract stones.

Endoscopic ureteral incision using the holmium:YAG laser

Abstract Background: We reviewed the results of endoscopic ureteral incision for benign ureteral stricture, ureteropelvic junction obstruction and ureteroenteroanastomotic stricture using the holmium laser.

Lactate dehydrogenase, Gleason score and HER-2 overexpression are significant prognostic factors for M1b prostate cancer

It has not been elucidated whether certain types of M1b prostate cancer (M1b PC) are associated with a poor outcome. The present study retrospectively identified predictive factors related to the outcome of M1b PC. The subjects were 104 patients who attended our hospital and received a diagnosis of M1b PC. The observation period ranged from 4 to 122 months (median, 43 months). The parameters investigated were: T classification, N classification, Gleason score (GS), pretreatment prostate-specific antigen (PSA) level, extent of disease (EOD) grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), calcium, and hemoglobin (Hb) levels, platelet count, and the status of HER-2 overexpression as determined with a Hercep Test(TM) Kit using initial needle biopsy specimens for diagnosis. Log-rank test and Cox univariate analysis identified the following factors with statistically significant differences: pretreatment PSA ≥ 192, N1, GS ≥ 8, EOD grade 3+4, high LDH, high ALP, low Hb, and HER-2 overexpression. Multivariate Cox proportional hazard analysis identified the factors GS ≥ 8, high LDH, and HER-2 overexpression with significant differences. The hazard ratio was 5.962, 2.465, and 2.907, respectively, and the probability value was P=0.0218, P=0.0207 and P=0.0090, respectively. When the subjects with GS ≥ 8, high LDH, and HER-2 over-expression were classified as the high-risk group, the 5-year cause-specific survival rate was 51.2, 29.6, and 20.0%, respectively. The present study showed that M1b PC patients with GS ≥ 8, high LDH, and HER-2 overexpression have a very poor outcome and thus, should be treated as a high-risk group requiring close follow-up.

An immunohistochemical study of chromogranin A and human epidermal growth factor-2 expression using initial prostate biopsy specimens from patients with bone metastatic prostate cancer

To investigate, using prostate needle‐biopsy specimens at diagnosis from patients with bone metastatic prostate cancer, whether the relationship between neuroendocrine (NE) cell differentiation and human epidermal growth factor‐2 (HER‐2) expression is a prognostic factor for outcome.