Comparison of mirabegron and vibegron for clinical efficacy and safety in female patients with overactive bladder: a multicenter prospective randomized crossover trial.

PURPOSE: To compare the efficacy and safety of mirabegron and vibegron in female OAB patients. METHODS: We conducted a multicenter, prospective, randomized crossover study of female patients with OAB. The patients were assigned to Group MV (mirabegron for 8 weeks, followed by vibegron for 8 weeks) or group VM (vibegron for 8 weeks, followed by mirabegron for 8 weeks). The primary endpoint was the change in OABSS from baseline, and the secondary endpoint was the change in FVC parameters. After completion of the study, each patient was asked which drug was preferable. RESULTS: A total of 83 patients were enrolled (40 and 43 in groups MV and VM, respectively). At 8th and 16th week, 33 and 29 in Group MV and 34 and 27 in Group VM continued to receive the treatment. The change in PVR was not significantly different between treatment with mirabegron and vibegron. The changes in OABSS, nighttime frequency, mean, and maximum voided volume were similar between mirabegron and vibegron. The mean change in the daytime frequency was greater in the vibegron than in the mirabegron. Of the 56 patients, 15 (27%) and 30 (53%) preferred mirabegron and vibegron, respectively. The remaining 11 patients (20%) showed no preference. The change in the urgency incontinence score during vibegron was better in patients who preferred vibegron to mirabegron. CONCLUSION: The efficacies of mirabegron and vibegron in female patients was similar. The patients' preference for vibegron could depend on the efficacy of vibegron for urgency incontinence.

Nocturia and sleep quality after transurethral resection of the prostate.

OBJECTIVES: To 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. METHODS: A 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. RESULTS: Overall, 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. CONCLUSIONS: Transurethral 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.

α1D/A-adrenoceptor antagonist naftopidil for the male lower urinary tract symptoms associated with benign prostatic hyperplasia: efficacy of dose increase therapy.

OBJECTIVES: To 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: A 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.

Effect of imidafenacin on nocturia and sleep disorder in patients with overactive bladder.

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.

New class azaphilone produced by a marine fish-derived Chaetomium globosum. The stereochemistry and biological activities.

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.

[Optimum initial dose of silodosin for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia].

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.

Polymyxin B and low-dose hydrocortisone treatment in a patient with uroseptic shock in a rural health unit.

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.

The relationship between the CD Cotton effect and the absolute configuration of FD-838 and its seven stereoisomers.

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.

Chaetomugilins, new selectively cytotoxic metabolites, produced by a marine fish-derived Chaetomium species.

Chaetomugilins A-F have been isolated from a strain of Chaetomium globosum originally isolated from the marine fish Mugil cephalus, and their absolute stereostructures have been elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, some chemical transformations and an X-ray analysis. These compounds exhibited significant growth inhibition against cultured P388 cells and HL-60 cells. In addition, chaetomugilins A, C and F showed selective cytotoxic activities against 39 human cancer cell lines.

Cell-adhesion inhibitors produced by a sea hare-derived Periconia sp.

Peribysin J and macrosphelide M have been isolated from a strain of Periconia byssoides originally isolated from the sea hare Aplysia kurodai. Their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some chemical transformations including the modified Mosher's method. These fungal metabolites inhibited the adhesion of human-leukemia HL-60 cells to human-umbilical-vein endothelial cells (HUVEC).

Case report of renal pelvic adenocarcinoma associated with a renal stone that produced carbohydrate antigen 125 and carbohydrate antigen 19-9.

A 68-year-old man underwent left side simple nephrectomy for symptomatic severe hydronephrosis with decreased function due to a renal stone. Because of severe adhesion around the kidney, the renal pelvic wall was torn during the operation. Pathological diagnosis was papillary adenocarcinoma of the renal pelvis with positive staining for carbohydrate antigen 125 (CA125) and carbohydrate antigen 19 9 (CA19-9). Retrospective analysis of preoperative blood sample showed a high level of CA125 and CA19-9. Four-cycle adjuvant chemotherapy with paclitaxel/carboplatin (TJ regimen) was performed. However, local recurrence developed 1 month after the termination of chemotherapy. Although papillary adenocarcinoma of the renal pelvis is extremely rare, the possibility of renal pelvic tumor should be kept in mind for patients who have a long-standing renal stone and hydronephrosis with irregularity at the renal pelvic wall. CA125 and CA19-9 can be useful markers for upper urinary tract tumor.

(R)-3'-(3-methylbenzo[b]thiophen-5-yl)spiro[1-azabicyclo[2,2,2]octane-3,5'-oxazolidin]-2'-one, a novel and potent alpha7 nicotinic acetylcholine receptor partial agonist displays cognitive enhancing properties.

Recent studies have suggested that the alpha7 nicotinic acetylcholine receptors play important roles in learning and memory. Herein, we describe our research of the structure-activity relationships (SAR) in a series of (S)-spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin]-2'-ones bearing various bicyclic moieties to discover novel alpha7 receptor agonists. Through a number of SAR studies on the series, we have found out that inhibition of CYP 2D6 isozyme, which was a primary obstacle for the previously identified compound, was avoidable by the introduction of bicyclic moieties. Chemical optimization of the series led to the identification of a novel and potent alpha7 nicotinic acetylcholine receptor partial agonist 23. This compound not only possessed high binding affinity (K(i) = 3 nmol/L) toward the alpha7 receptor but also showed agonistic activity even at a concentration of 0.1 micromol/L. In addition, compound 23 improved cognition in several rat models, which might suggest the potential of the alpha7 receptor partial agonist for the treatment of neurological disorders including cognitive dysfunction.

Cell-adhesion inhibitors produced by a sea hare-derived Periconia sp. II. Absolute stereostructures of peribysins H and I.

Peribysins H (1) and I (2) have been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai. Their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using ID and 2D NMR techniques and some chemical transformations including the modified Mosher's method. These metabolites inhibited the adhesion of human-leukemia HL-60 cells to HUVEC.

A case of metastatic renal cell carcinoma to the ovary.

A 52-year-old woman had a pathological fracture of the right femur. On histopathological examination bone metastasis from renal cell carcinoma was suspected. Abdominal computed tomography showed a heterogeneous mass (9.1 x 7.8 x 6.5 cm) in the left kidney and a cystic multilocular mass (12 x 10 cm) in the pelvis. Bone scintigraphy revealed an abnormal uptake in the left coracoid process, right third rib, and right distal femur and proximal tibia. Clinical diagnosis was left renal cancer with multiple bone metastases (cT2NOM1, stage IV) and a right ovarian tumor. We performed left radical nephrectomy and resection of right ovarian tumor by bilateral adnexectomy. On histopathological examination, the left kidney tumor was diagnosed as renal cell carcinoma (clear cell carcinoma with chromophobe component, G2 > G1). The ovarian tumor consisted of carcinoma of clear cell type (G2) that resembled components of left renal cell carcinoma, confirming the diagnosis of metastatic renal clear cell carcinoma to the ovary. Although she underwent immunotherapy with interferon, she died 10 months after nephrectomy. Metastasis to the ovary from renal clear cell carcinoma is very rare and only 18 cases have been reported in the literature. This rarity may be related to the difficulty of differential diagnosis between metastatic renal cell carcinoma to the ovary and primary ovarian clear cell carcinoma. Elaborate analysis of microscopic features and immunohistochemical profiles may help in the distinction of this metastatic lesion.

Absolute stereostructures of cell-adhesion inhibitors, peribysins A, E, F and G, produced by a sea hare-derived Periconia sp.

Peribysins E-G (1-3) have been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai. Their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some chemical transformations. In addition, the absolute configuration of peribysin A (4), previously undetermined, has been established by conversion to 2 and 3. All these metabolites inhibited the adhesion of human-leukemia HL-60 cells to HUVEC.

Absolute stereostructures of cell adhesion inhibitors, macrosphelides H and L, from Periconia byssoides OUPS-N133.

Macrosphelide L has been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai, and the absolute stereostructures of this material and macrosphelide H, previously undetermined, have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some chemical transformation. (R)-Methyl 3-p-bromobenzoyloxy-5-oxohexanoate has been synthesized for configurational assignments of macrosphelide H. These macrosphelides inhibited the adhesion of human-leukemia HL-60 cells to HUVEC.

[A case of spermatic granuloma difficult to differentiate from malignant tumor].

A 33-year-old man visited our hospital with complaint of painless left intrascrotal mass. A hard and rough induration in contact with the left testis was palpable. The laboratory data including beta-human churionic gonadotropin, alpha fetoprotein and lactate dehydrogenase were normal. Ultrasound sonography showed a large hypoechoic lesion at the left epididymis. Surgical exploration of this lesion indicated a malignant tumor of the epididymis or spermatic cord, and left high orchiectomy was performed. A milk-white nodule 6 cm in diameter was found in the resected specimen. Pathological diagnosis was spermatic granuloma. Fourteen cases of spermatic granuloma have been reported in the last twenty years in Japan. All of them were relatively small nodules and epididymectomy was performed for most of them. We selected radical orchiectomy because of a large nodule with suspicion of malignant lesion.

[Usefulness of nocturnal urethral indwelling catheter for treating bladder dysfunction with nocturnal polyuria: case report of 3 women].

Clean intermittent catheterization is a well-known procedure of urinary drainage for patients who are unable to empty the bladder sufficiently. However, some patients with bladder dysfunction and nocturnal polyuria fail to obtain the benefits of intermittent catheterization and have annoying symptoms of nocturnal incontinence and low-compliance bladder, which threaten both their quality of life and renal function. We report the usefulness of nocturnal urethral indwelling catheterization using a specially designed catheter to treat patients (three women) with lower urinary tract dysfunction and nocturnal polyuria. Case 1: A 45-year-old woman with mental retardation suffered from difficulty of micturition and residual urine. A nocturnal urethral indwelling catheter freed her from difficulty with micturition and residual urine. Case 2: A 28-year-old woman with spina bifida and neuropathic bladder dysfunction suffered from urinary incontinence and recurrent pyelonephritis. The recurrent pyelonephritis was prevented and bladder compliance was improved with use of the nocturnal urethral indwelling catheter. Case 3: A 66-year-old woman with cervical myelopathy and multiple episodes of cerebral infarction suffered from nocturnal urinary incontinence. She underwent clean intermittent catheterization by her husband. Use of the nocturnal urethral indwelling catheter solved the problem of her nocturnal incontinence and relieved her husband of her nocturnal care. Nocturnal urethral indwelling catheterization is useful for treatment of nocturnal incontinence and recovery of bladder compliance in patients with lower urinary tract dysfunction and nocturnal polyuria.

[Tumor enucleation for pelvic schwannoma: a case report].

A 36-year-old man with a complaint of pollakisuria visited our hospital. A non-displaceable, palm-sized tumor was palpable in the lower abdomen. Laboratory data were normal except for slightly high serum S100 protein. Intravenous pyelography revealed hydronephrosis on the right side and deviation of the bladder to the left. Computed tomogaphy revealed a heterogenous tumor in the pelvis with a cystic lesion and calcification. The tumor was 16 x 12 x 11 cm in size and in contact with the sacrum. The tumor was extirpated following diagnosis as a benign schwannoma by needle biopsy. The pelvic cavity was occupied by the tumor rigidly adhered to the sacrum. Although serious complications, such as bleeding and nerve injury were apprehended, we incised the tumor capsule and enucleated the contents as much as possible. The histopathological diagnosis of the resected specimen was benign schwannoma, type Antoni A. In the last 10 years, 37 cases of pelvic schwannoma have been reported in the Japanese literature. In most of them, surgical extirpation was difficult to perform because of adhesion to the sacrum. If the tumor is confirmed benign from histopathologic findings preoperatively, tumor enucleation may become a therapeutic option.

The impact of abdominal aortic calcification and visceral fat obesity on lower urinary tract symptoms in patients with benign prostatic hyperplasia.

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.