Sepsis has a high mortality rate; thus, in the intensive care unit, early diagnosis and adjunctive treatments are crucial. However, generally, most patients with sepsis from rural area initially visit the emergency department at a rural hospital and are managed in general medical wards in Japan. Here we report on an 81-year-old Japanese female manifesting septic shock caused by the upper urinary tract infection of extended-spectrum beta-lactamase-producing Escherichia coli secondary to the left ureter obstruction by the urothelial carcinoma. Broad-spectrum antibiotics were administered. Although critical for the source control of infection, drainage of the ureteropelvic junction could not be performed immediately because of catecholamine-resistant hypotension. Hence, we administered polymyxin B-immobilized fiber column direct hemoperfusion, followed by low-dose hydrocortisone administration. After 8 hours of infusion, she recovered from the septic shock and successfully underwent emergency percutaneous nephrostomy. This presented strategy may provide a new resolution of catecholamine-resistant patients in urosepsis.

OBJECTIVES:To investigate the impact of abdominal aortic calcification and visceral fat area (VFA) on lower urinary tract symptoms (LUTS) and clinical parameters in patients with benign prostatic hyperplasia (BPH).METHODS:We retrospectively studied 250 patients with LUTS associated with BPH. Each participant was examined with routine examination including measurement of various data; (1) voided volume (VV), maximum urinary flow rate on free uroflowmetry, (2) postvoid residual urine volume and prostate volume using transabdominal ultrasound, (3) International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS), and (4) aortic calcification index (ACI) and VFA were measured by abdominal CT.RESULTS:Mean age of the patients was 72.4 ± 9.6 years. ACI significantly correlated with VV (P = 0.0392) and tended to correlate with maximum urinary flow rate, while ACI did not correlate with subjective symptoms. VFA significantly correlated with nocturia score of IPSS (P = 0.0177) and frequency score of OABSS (P = 0.0166) and tended to correlate with urgency score of IPSS and maximum urinary flow rate.CONCLUSIONS:Aortic calcification index (ACI) correlated with only objective parameters, while VFA correlated with only storage symptoms. This study suggested that abdominal aortic calcification and VFA have certain influence on LUTS and clinical parameters in patients with BPH.

Anthcolorins A–F were isolated from a strain of Aspergillus versicolor originally isolated from the sea urchin Anthocidaris crassispana, and their absolute stereostructures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, an X-ray crystal-structure analysis and CD spectra. These compounds were unique tetrahydropyrane diterpene type metabolites with oxoindoline at C-3, and some of them exhibited significant growth inhibition against cultured P388 cells.

A continuous investigation of secondary metabolites produced by the sponge-derived fungus, Gymnascella dankaliensis, has yielded a new polyketide tyrosine derivative, dankastatin C (3) and the known steroid, demethylincisterol A3 (4), which was originally found from a Homaxinella marine sponge. The stereostructure of the new compound has been determined based on the analysis of 1D and 2D NMR data. Dankastatin C (3) showed potent cell growth inhibitory activity against the murine P388 cell line.

A new metabolite, pileotin A, was isolated from a strain of Aspergillus fumigatus originally obtained from the sea urchin Toxopneustes pileolus together with the known compound oxalicine B. The relative stereostructure of pileotin A was elucidated based on spectroscopic analyses, including 1D and 2D NMR techniques. This unique pyridino-α-pyrone sesquiterpene type metabolite has spiro-δ-lactone at C-4.

Three new metabolites, chaetomugilin S, dechloro-chaetomugilin A and dechloro-chaetomugilin D, were isolated from a strain of Chaetomium globosum originally obtained from the marine fish Mugil cephalus, and their absolute stereostructures were elucidated based on the basis of spectroscopic analyses, including 1D and 2D NMR techniques and some chemical transformations. Particularly, chaetomugilins T and U are the first compouds without a chlorine atom in azaphilones isolated from this fungal strain, to date. In addition, these compounds moderately inhibited the growth of cultured P388, HL-60, L1210 and KB cell lines.

ObjectivesTo examine the efficacy of dose increase therapy in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia who responded poorly to 50 mg/day of naftopidil.MethodsA total of 95 patients received 50 mg/day of naftopidil for 8 weeks. After this treatment period, they were divided into two groups: the poor responders were defined as those who either had an International Prostate Symptom Score‐Quality of Life ≥4 or with an International Prostate Symptom Score‐Quality of Life of 3 whose International Prostate Symptom Score‐Quality of Life improved <2 points (group A). All other patients were defined as responders to naftopidil 50 mg/day (group B). The dose of naftopidil was increased to 75 mg/day in group A, and maintained at 50 mg/day in group B. The treatment was continued for a further 8 weeks.ResultsThe prostate volume at the baseline was significantly larger in group A than group B. The improvement of International Prostate Symptom Score total score, International Prostate Symptom Score‐Quality of Life, and voided volume after 8 weeks was significantly better in group B than in group A. However, there was no significant difference in the changes of all parameters between the two groups after 16 weeks.ConclusionsA dose increase to 75 mg/day is an effective treatment strategy in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia who responded poorly to an initial dose of 50 mg/day of naftopidil. Furthermore, a starting dose of 75 mg/day should be considered in patients with a large prostate volume, as this is a predictive factor for dose increase.

Objective: To evaluate the efficacy of imidafenacin on nocturia and sleep disorder in patients with overactive bladder (OAB). Patients and Methods: A prospective multicenter study of imidafenacin 0.1 mg twice daily for patients with OAB and nocturia was conducted. At baseline and at week 4 and 8, patients were assessed using the overactive bladder symptom score (OABSS), frequency volume charts (FVC) and the Pittsburgh Sleep Quality Index (PSQI). Results: Treatment with imidafenacin significantly improved OAB symptoms. Imidafenacin also improved PSQI, especially subjective sleep quality, sleep latency and daytime dysfunction. In FVC, the number of daytime voids and nighttime voids significantly decreased and average voided volume significantly increased after imidafenacin. Subanalysis of FVC based on the patients’ age revealed that nocturnal polyuria was more often found in patients aged 75 years or over than in those aged under 75 years (79 vs. 55%, p < 0.05). Treatment with imidafenacin significantly reduced the nocturnal polyuria index only in patients aged 75 years or over. Conclusions: Imidafenacin can improve nocturia and sleep disorder in patients with OAB. The efficacy of imidafenacin on nocturia is attributable to an increase in bladder capacity and a decrease in nocturnal urine volume. We conclude that imidafenacin is an effective and safe drug for nocturia in patients with OAB.

We investigated the optimum initial dose and timing of administration of α1A-adrenoceptor antagonist silodosin for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH/LUTS). Ninety-eight patients were given a 4 mg dose after breakfast (group A), 4 mg after supper (group B), or 4 mg after breakfast and after supper (group C). At baseline, 4, 8 and 12 weeks after treatment, we assessed International Prostate Symptom Score (IPSS) and quality of life (QOL) index. Twenty-five percent or less improvement of total IPSS and no improvement of QOL index compared with baseline were defined as treatment failure at each evaluation point. Otherwise treatment was considered effective. In group A and group B, patients with treatment failure at 4 or 8 weeks after treatment, the dose of silodosin was increased to 8 mg daily. At the end of the study, 83 patients were evaluable. At 12 weeks after treatment, 20 of the 31 patients in group A and 22 of the 29 patients in group B remained on the 4 mg dose ; silodosin was effective in 65 and 76% of the patients, respectively. When patients with dose escalation were included, silodosin was effective in 81 and 90% of the patients, respectively. Silodosin was effective in 18 of the 23(78%) patients in group C, although improvement of total IPSS and voiding symptom score of IPSS at 12 weeks after treatment was better in group C than in group A or group B, the difference was not significant. In patients with IPSS less than 20, the degree of improvement of IPSS was similar among the 3 groups. In contrast, in patients with IPSS of 20 or greater the degree of improvement was better in group C than in group B or group C, but the difference was not significant. Storage symptom score of IPSS was significantly improved in all 3 groups without any significant difference among the 3 groups. Three patients (52, 59 and 76 years old) experienced abnormal ejaculation. In conclusion, 4 mg of silodosin daily showed effectiveness against BPH/LUTS, but 8 mg of silodosin daily might be better for patients with severe LUTS.

ObjectivesTo evaluate the clinical efficacy of transurethral resection of the prostate on nocturia and sleep disorders in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.MethodsA prospective multicenter study including lower urinary tract symptoms suggestive of benign prostatic obstruction patients with nocturia (twice or more) undergoing transurethral resection of the prostate was carried out. All patients were assessed using the International Prostate Symptom Score and the Pittsburgh Sleep Quality Index at baseline, and 6 months after transurethral resection of the prostate.ResultsOverall, 49 patients were included in the study. A total of 20 of them (41%) had a sleep disorder defined as a score of 5.5 or more on the Pittsburgh Sleep Quality Index global score. The nocturia score significantly correlated with component 4 of the Pittsburgh Sleep Quality Index (habitual sleep efficiency). Nocturia significantly decreased after transurethral resection of the prostate from 3.0 ± 1.2 to 1.9 ± 0.8, whereas the global Pittsburgh Sleep Quality Index score did not. In 20 patients with a sleep disorder before transurethral resection of the prostate, subjective sleep quality (component 1) and habitual sleep efficiency (component 4) significantly decreased after transurethral resection of the prostate, but this was not the case for the global Pittsburgh Sleep Quality Index score. In 16 patients with a persistent sleep disorder after transurethral resection of the prostate, International Prostate Symptom Score, voiding and storage symptoms score were higher than those of patients without a sleep disorder, although the nocturia score improved equivalently in both groups.ConclusionsTransurethral resection of the prostate diminishes nocturnal urinary frequency and partly improves sleep quality in patients with nocturia and lower urinary tract symptoms suggestive of benign prostatic obstruction. A persistent sleep disorder after transurethral resection of the prostate is associated with persistent voiding and storage symptoms.

Four new metabolites, chaetomugilins P-R and 11-epi-chaetomugilin I, were isolated from a strain of Chaetomium globosum originally obtained from the marine fish Mugil cephalus, and their absolute stereostructures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR techniques and various chemical transformations. Particularly, the skeleton of chaetomugilin P is different from that of other azaphilones isolated from this fungal strain to date. In addition, these compounds significantly inhibited the growth of cultured P388, HL-60, L1210 and KB cell lines.

Three new metabolites having a spiro-heterocyclic gamma-lactam core, cephalimysins B-D (1-3), as well as FD-838 (4) were isolated from a culture broth of Aspergillus fumigatus that was originally separated from the marine fish Mugil cephalus. Compounds 1-3 are the diastereomers of 4. Compounds 2 and 3 exhibit an opposite absolute configuration at a spiro carbon to that of other known naturally occurring spiro-heterocyclic gamma-lactams. In addition, we succeeded in the chemical transformation of the four natural products (1-4) into their epimers (1'-4') at C-8 to afford all the stereoisomers of FD-838 (4) with three stereogenic centers. Consequently, the relationship between the absolute configuration at stereogenic centers and the CD Cotton effects for these compounds could be unambiguously established. All of the compounds except 1 moderately inhibited the growth of cultured P388 and HL-60 cell lines.

AbstractGymnastatins I (I), J (II), and K (III) are isolated from the sponge‐derived title fungus.

11- and 4'-epichaetomugilin A were isolated from a strain of Chaetomium globosum that was originally isolated from the marine fish Mugil cephalus 11-Epichaetomugilin A is the first compound to have an opposite absolute configuration at C(11) to that of other azaphilones isolated to date. Their absolute configurations were elucidated on the basis of spectroscopic analyses, including 1D- and 2D-NMR techniques, and some chemical transformations. 11-Epichaetomugilin A weakly inhibited the growth of cultured P388 cells and HL-60 cells (IC50 88.9 and 66.7 mu M resp.).

The Halichondria sponge-derived fungus, Gymnascella dankaliensis, was cultured in a malt extract medium containing the bromine source.Three new metabolites, gymnastatins I (5)-K ( 7), have been isolated from the mycelial MeOH extract.The spectroscopic analyses using 1D and 2D NMR techniques have established the stereostructures of 5-7 in which chlorine atoms in gymnastatins A (1)-C (3) are respectively replaced by bromine atoms.All of the isolated metabolites (5-7) exhibited growth inhibition against the P388 cancer cell line.Furthermore, gymnastatins I (5) and J (6) showed appreciable growth inhibition against the human cancer cell lines.

OBJECTIVES:To evaluate the clinical efficacy and tolerability of propiverine and solifenacin in female patients with overactive bladder (OAB).METHODS:A prospective nonrandomized crossover study of propiverine 20 mg and solifenacin 5 mg was conducted. Female OAB patients were assigned alternately to treatment with propiverine for 8 weeks then solifenacin for 8 weeks (Group P-S) or solifenacin for 8 weeks then propiverine for 8 weeks (Group S-P). At baseline, 8th week and 16th week, symptoms were assessed using overactive bladder symptom score (OABSS).RESULTS:A total of 121 patients were enrolled. Overall, 38 patients (31.4%) discontinued or dropped out and 83 patients were available for analysis (39 in Group P-S and 44 in Group S-P). In both groups, the total score and each score of OABSS were significantly improved after 8 weeks compared with baseline. In only Group P-S (changing over from propiverine to solifenacin), urgency score in the 16th week was further improved significantly compared with the 8th week. The most bothersome symptom at baseline was urgency incontinence (50.6%), followed by urgency (37.3%). Even after symptom improvement, more than half of the patients were bothered by urgency or urgency incontinence. The incidence of adverse events of moderate and severe grade was higher during propiverine treatment than solifenacin (11.1% vs 2.9%, P = 0.039).CONCLUSION:Propiverine 20 mg and solifenacin 5 mg were effective for treating female OAB patients. Urgency was further improved after switching from propiverine to solifenacin, but not after switching from solifenacin to propiverine. Solifenacin was better tolerated than propiverine.

In order to apply ion beam figuring (IBF) to final shape correction of the substrates of projection optics for EUVL, ion beam machining characteristics such as high-spatial frequency roughness (HSFR) and mid-spatial frequency surface roughness (MSFR) of ULE® substrate were investigated. Our previous research confirmed that the surface roughness of the ULE® machined by Ar+ ion beam with energy of 3–10 keV decreases with decreasing the ion beam energy. Therefore, we have conducted our research on ion beam machining of ULE® substrate by Ar+ ion beam with energy from 0.2 to 2 keV. The HSFR and MSFR of the mechanically pre-finished ULE® substrate were 0.06 and 0.07 nm rms, respectively; whereas, the HSFR and MSFR of the substrate irradiated by Ar+ ion beam at energy of 0.3 keV were less than 0.10 and 0.08 nm rms, respectively. The HSFR is the best result among our previous and other current research.

Chaetomugilins G and H were isolated from a strain of Chaetomium globosum that was originally isolated from the marine fish, Mugil cephalus , and their absolute stereostructures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, and chemical transformation. In addition, the absolute configuration of chaetoviridin C was established by derivatization from chaetomugilin A. These compounds exhibited a growth inhibitory activity against cultured P388, HL-60, L1210 and KB cells.