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Abstract:We developed a local anesthetic procedure for three-dimensional 26-core prostate biopsy (3D26PBx), a combination of transperineal 14-core biopsy (TP14PBx) and transrectal 12-core biopsy (TR12PBx). At first, a periapical triangle, confined by the levator ani, the rhabdosphincter and the external anal sphincter muscle, was made visible by transrectal ultrasound. After administration of 1 mL of 1%-lidocaine into the midline perineal skin 1.5 cm above the anus, we inserted a spinal needle toward the periapical triangle for injection of 1.5-2.0 mL of 1%-lidocaine and performed the TP14PBx. After administration of the periprostatic nerve block with 10 mL of 1%-lidocaine, we performed the TR12PBx. The efficacy of the procedure was evaluated prospectively in 45 consecutive men undergoing the 3D26PBx. The 3D26PBx was completed with just local anesthesia in all patients. The pain levels, assessed by an 11-point visual analog scale, were not different between the TP14PBx and the TR12PBx.

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? C‐reactive protein (CRP) level has been shown to be a significant prognostic factor for various malignancies, including urothelial carcinoma treated surgically. Apart from CRP level, several prognostic factors have been identified for advanced urothelial carcinoma patients receiving a second‐line chemotherapy. CRP could also be a significant prognostic factor for advanced urothelial carcinoma patients receiving a second‐line chemotherapy. CRP kinetics, the dynamic change of CRP concentration, has a strong impact on survival. Adding to the baseline CRP status at the start of treatment, the normalization of CRP during treatment is significantly associated with prognosis. The period with normalized CRP level was strongly correlated with survival period. Therefore, CRP could be a potential biomarker for advanced urothelial carcinoma patients. OBJECTIVE To assess the impact of C‐reactive protein (CRP) kinetics, the effect of dynamic changes of CRP concentration on the survival of patients with locally advanced or metastatic urothelial carcinoma (UC) treated by single chemotherapeutic regimen including cisplatin was examined. PATIENTS AND METHODS Eighty patients with advanced UC, who failed treatment of advanced UC with the first‐line chemotherapy or who received perioperative treatment of neoadjuvant or adjuvant settings, were treated with gemcitabine, etoposide and cisplatin (GEP) as second‐line chemotherapy. Patients were divided into three groups according to CRP kinetics based on baseline and nadir CRP concentrations. Patients whose baseline CRP levels were <5 mg/L, patients whose baseline CRP levels were ≥5 mg/L and normalized (<5 mg/L), and patients whose baseline CRP levels were ≥5 mg/L and never normalized were assigned to non‐elevated, normalized and non‐normalized CRP groups, respectively. The prognostic impact of CRP kinetics and the correlation between normalized CRP period and overall survival period were determined. RESULTS In 46 (57%) of the 80 patients, CRP levels were elevated at the diagnosis of advanced UC. During treatment, after a median follow‐up period of 12 months CRP levels were normalized in 24 (71%) of 34 patients, whereas CRP levels remained elevated in the remaining 10 patients. Overall survival rates were significantly different between the non‐elevated, normalized, and non‐normalized CRP groups (P < 0.001), with 1‐year survival rates of 72, 51 and 14%, respectively. On multivariate analysis including Eastern Cooperative Oncology Group performance status, visceral metastasis, number of metastatic sites, previous definitive surgery, anaemia, baseline and nadir CRP levels (mg/L), and CRP kinetics status, CRP kinetics was an independent and significant factor for overall survival. The normalized CRP period was significantly correlated with the overall survival period in 52 patients who died. CONCLUSIONS CRP kinetics is significantly associated with the prognosis and survival ...

The structures of two protein factors, S-II and S-II', that specifically stimulate RNA polymerase II from Ehrlich ascites tumor cells were compared. The two proteins behaved differently on CM-cellulose chromatography and on isoelectric focusing, although they were shown to have common antigenicity. The following findings strongly suggest that S-II and S-II' have the same primary structure, but that S-II' is more extensively phosphorylated than S-II: (1)S-II an S-II' gave identical peptide maps when digested with various proteases. (2) S-II' that had been treated with alkaline phosphatases had the same mobility on sodium dodecyl sulfate-polyacrylamide gel as S-II, indicating that it could be converted to S-II by hydrolysis of its phosphate residues. (3) S-II' was phosphorylated more than S-II when Ehrlich ascites tumor cells were labeled in vivo with [32P]orthophosphate.

Laninamivir octanoate (LO) is a new neuraminidase inhibitor for inhalation. The objectives of this study were to model the population pharmacokinetics of LO and its active metabolite laninamivir after inhaled administration of LO using a pooled population of healthy subjects, and adult and pediatric patients with influenza virus infection from 8 clinical studies, and to evaluate covariate effects on pharmacokinetics. The pharmacokinetics of LO and laninamivir in plasma and urine are well-described by structural models that consist of a 2-compartment model for LO with instantaneous bolus input and first-order elimination; and a 1-compartment model for laninamivir with formation of laninamivir via the metabolic pathway from LO in systemic circulation, entry of laninamivir from the respiratory tract compartment, and linear elimination. Creatinine clearance was identified as a covariate of apparent total clearance for LO and renal clearances for LO and laninamivir, with the largest effect on laninamivir exposure. Body weight was identified to affect distribution volumes of LO and laninamivir and the metabolic clearance of LO; however there was no notable effect on exposures across the wide body weight range evaluated. The population pharmacokinetic model also provides insight into the likely kinetics of drug disposition in the respiratory tract following inhaled administration.