The pharmacokinetics of vancomycin (VAN) was retrospectively examined based on trough concentrations at large scale to identify pharmacokinetic differences between Japanese hematologic malignancy and non-malignancy patients. Data from 261 hematologic malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN estimated by an empirical Bayesian method, were collected and analyzed. Our results showed significantly higher values for VAN clearance and shorter elimination half-lives in patients with hematologic malignancies than non-malignancy patients. In addition, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to hematologic malignancies. In conclusion, since in hematologic cancer patients VAN clearance is increased, the blood concentration of VAN becomes lower than expected and this may contribute to the survival of resistant bacteria when VAN is administered at low doses. These results suggest that early monitoring of VAN levels in hematologic cancer patients might be recommended to maintain desired effects without side-effects.

Objective: Many reports on varicoceles suggest improved spermatic findings and increased pregnancy rates after correction of these lesions. Early repair during adolescence has been advocated , since clinically apparent varicoceles may affect testicular volume and sperm production in the future. We examined the efficacy of microsurgical varicocelectomy, and aimed to establish predictive parameters useful for ascertaining whether varicocele repair provides any benefits in adolescents and adults. Methods: We carried out microsurgical varicocelectomy on nine boys and 19 men. In adolescents, catch-up growth of the testis, expressed by pre-and postoperative ratios of left and/or right testicular volume, grade and serum level of follicle-stimulating hormone (FSH) were evaluated. In adults, the ratio of sperm concentration improvement, grade, testicular volume, preoperative sperm concentration and serum FSH level were evaluated. All subjects were followed for 12 months. Results: Catch-up growth was seen in 62.5% of boys. FSH level was significantly lower in boys with catch-up growth than in boys without catch-up growth. Improved sperm concentration was seen in 73.6% of adults. FSH level was significantly lower in adults with improved sperm concentration than in patients without improved sperm concentration. No correlations were seen between other parameters and catch-up growth in adolescents, or sperm concentration improvement in adults. Conclusions: Microsurgical varicocelectomy as a treatment for varicoceles with low FSH might be effective and the relevant predictive parameter for testicular development and function after surgery might be serum FSH level in both adults and adolescents.

Background and Aims:We carried out clinostat and parabolic flight experiments to examine the effects of a microgravity (µG) environment on human sperm motility.Methods: Semen samples were obtained manually from 18 healthy men (aged 27.4 ± 5.4 years) who had given their informed consent. In clinostat experiments, samples that were left stationary were used as a stationary control. Samples rotated vertically and horizontally were used as a rotation control and a clinostat rotation, respectively. In parabolic flight experiments using a jet plane, sperm motility was compared for each parameter at µG, 1G and 2G. The state of 1G during the flight was used as a control. Sperm motility was determined using an automatic motility analyzer HT-M2030 in a microgravity environment.Results: All parameters of sperm motility tended to be lower in clinostat rotation compared with rotation control at both low-speed and high-speed, but the differences were not statistically significant. In parabolic flight, sperm motility and parameters of linear movement were decreased (P < 0.05). There was no significant difference between µG and 2G, but sperm motility was significantly decreased at µG than at 1G. Conclusions:

We transferred the adventitious gene pCAGGS-lacZ to mouse testes with the use of a square-wave electroporator and investigated the efficiency of gene transfer (GT) and the influence of the procedure on testicular damage and spermatogenesis. Mice were divided into 5 groups: (1-2) injection of gene/phosphate-buffered saline (PBS) into the interstitial space followed by electroporation (EP), (3) EP alone, (4-5) injection of gene/PBS without EP. The presence of the lacZ gene was determined by X-gal (5-bromo-4-chloro-3-indolyl-␤-D-galactopyranoside) staining and the polymerase chain reaction (PCR). The influence of transfer on spermatogenesis was assessed by evaluating the seminiferous tubules according to the Johnsen score (JS). TdT-mediated dUTP-biotin nick end-labeling (TUNEL) staining was performed for the detection of apoptosis in the testes to evaluate the testicular damage caused by GT, and fertilization ability was assessed by mating male mice from each group with normal female mice at 1, 2, 4, 6, and 8 weeks after the procedure. LacZ expression was detected by X-gal staining and PCR for 4 weeks after GT in group 1. But in group 4, LacZ expression was not detected for all times. In groups 1 through 3, the JSs decreased gradually until 4 weeks and recovered at 6 and 8 weeks after GT. The JSs were significantly decreased at 4 weeks for groups 1 through 3 compared with groups 4 and 5. In groups 1 through 3, apoptotic cells were significantly more numerous at 1, 2, and 4 weeks after the procedure, and there were significant differences in their numbers between groups 1 through 3 and groups 4 and 5 until 4 weeks after the procedure. The number of offspring did not differ significantly between all groups. These results suggest that although spermatogenic damage caused by EP could present problems, GT by EP might be effective for transfecting germ cells or somatic cells and could be applicable for in vivo gene therapy for male infertility in the future.

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