Factors related to self-care behaviors among hospitalized patients with heart failure in Japan, based on the European Heart Failure Self-Care Behaviour Scale.

[Purpose] The characteristics of heart failure in hospitalized patients with poor self-care behaviors are unknown. We investigated factors associated with self-care behaviors by using the European Heart Failure Self-Care Behaviour Scale (EHFScBS) in heart failure patients based on three comprehensive concepts. [Participants and Methods] This was a cross-sectional single-center study of heart failure patients hospitalized at a tertiary-care hospital. We investigated age, gender, family living together/apart, employment, and the Specific Activity Scale (SAS). A physical therapist provided the EHFScBS one time to determine the patients' pre-hospital self-care behavior status. The 12 items of the EHFScBS were classified into the following three categories: Maintenance, Monitoring, and Management. [Results] The median age of the 39 consecutive patients was 81 years. A multiple regression analysis revealed that the factors exhibiting significant associations were the SAS score (ß=0.504) for Management and age (ß=-0.403) for the total EHFScBS score (adjusted by the number of hospitalizations for heart failure). Maintenance and Monitoring were not significantly associated with the survey items. [Conclusion] These data indicate that self-care education for hospitalized patients with heart failure leads to individualized approaches based on characteristics such as age and physical activity capacity.

Lead optimization of 2-hydroxymethyl imidazoles as non-hydroxamate LpxC inhibitors: Discovery of TP0586532.

Infectious diseases caused by resistant Gram-negative bacteria have become a serious problem, and the development of therapeutic drugs with a novel mechanism of action and that do not exhibit cross-resistance with existing drugs has been earnestly desired. UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is a drug target that has been studied for a long time. However, no LpxC inhibitors are available on the market at present. In this study, we sought to create a new antibacterial agent without a hydroxamate moiety, which is a common component of the major LpxC inhibitors that have been reported to date and that may cause toxicity. As a result, a development candidate, TP0586532, was created that is effective against carbapenem-resistant Klebsiella pneumoniae and does not pose a cardiovascular risk.

Changes of sexual function and perception in Japanese men: A 15-year cross-sectional community-based study.

OBJECTIVES: To investigate the longitudinal changes of sexual function of Japanese men. METHODS: From 1992 to 1993, we carried out a cross-sectional community-based study on sexual function in Japanese men aged 40-79 years. After 15 years, a follow-up study was carried out to determine longitudinal changes of their sexual function. Of the 319 participants in the initial study, 135 participated again in the follow-up study. Sexual function was assessed using the same validated questionnaire in the two studies. RESULTS: Erectile rigidity declined in men of each age decade at baseline (40s, 50s, 60s and 70s) of the initial study (P < 0.01, <0.01, <0.01 and <0.05). The frequency of sexual drive was significantly decreased in men aged in their 40s, 50s and 60s (P < 0.05, <0.01 and <0.01). Men aged in their 40s were dissatisfied with their decreased sexual function (P < 0.05). In contrast, men aged in their 70s were satisfied with their sexual life (P < 0.01). CONCLUSIONS: Over a 15-year period, the sexual function of Japanese men declined in each age decade. However, the perception of this decline differed among different age group. Most elderly Japanese men did not worry about their impaired sexual function.

Intravenous Preload of Mesenchymal Stem Cells Rescues Erectile Function in a Rat Model of Cavernous Nerve Injury.

INTRODUCTION: We evaluated the potential preventive effects and mechanisms of intravenously preloaded mesenchymal stem cells (MSCs) for erectile dysfunction (ED) in a cavernous nerve (CN) injury model. METHODS: Male Sprague-Dawley (SD) rats were used for this study. Rats were randomized into two groups. One group was intravenously preloaded with MSCs (1.0 × 10(6) cells in 1 mL total fluid volume) and the other was infused with medium alone (1 mL Dulbecco's modified Eagle's medium [DMEM]) for sham control, respectively. Crushed CN injury was induced immediately after infusion. The surgeon was blind to the experimental conditions (MSC or medium). MAIN OUTCOME MEASURES: To assess erectile function, we measured the intracavernous pressure (ICP) and arterial pressure (AP) at 1 hour and 2 weeks after CN injury. After measuring the initial ICP/AP of pre-injury (normal) male SD rats, they were randomized into the two groups and infused with MSCs or medium. PKH26-labelled MSCs were used for tracking. To investigate the mRNA expression levels of neurotrophins in the major pelvic ganglia (MPG), we performed real-time quantitative real-time polymerase chain reaction. RESULTS: The reduction of ICP/AP and area under the curve of ICP (ICP-AUC) in the MSC group was significantly lower than in the DMEM group (P < 0.05; P < 0.05) at 1 hour. The ICP/AP and ICP-AUC at 2 weeks post-injury in the MSC group was significantly higher than in the DMEM group (P < 0.01; P < 0.05). The preloaded PKH26-labelled MSCs were detected in the MPG and CN using confocal microscopy indicating homing of the cells to the injured nerve and ganglia. Glia cell-derived neurotrophic factor (GDNF) and neurturin, which are important neurotrophic factors for erection, had expression levels in MPG significantly higher in the MSC group than in the DMEM group (P < 0.01, 0.05). CONCLUSION: Intravenous preload of MSCs before a CN injury may prevent or reduce experimental ED.

[Polyorchidism: a case report and review of the literature].

A 10-year-old boy presented with a painless left scrotal mass that had been present for 2 years. Ultrasound examination revealed 2 left testes measuring 2.4 ml and 1.0 ml with the same echogenicity. Atsurgery, there were 2 similarly sized testes connecting with other spermatic vascular, but the supernumerary testis had no connection with the vas deferens. Histological findings showed immature testicular tissue without malignancy. We report the 26th case of polyorchidism in Japan and discuss this condition.

Correlation between erection hardness score and nocturnal penile tumescence measurement.

INTRODUCTION: The Erection Hardness Score (EHS) and the Sexual Health Inventory for men (SHIM) are patient-reported outcome scoring systems for erectile function. It is unclear which is more reliable for predicting the objective erectile function. AIM: The aim of this study was to evaluate whether the EHS could predict objective erectile function by measuring the maximal penile circumferential change (MPCC) with an erectometer. METHODS: The study included 98 patients who visited our clinic from 2005 to 2010. The erectile function was evaluated using the SHIM, EHS, and MPCC. The MPCC was measured with the largest circumferential change of three consecutive occurrences of nocturnal penile tumescence (NPT) determined using the erectometer. MAIN OUTCOME MEASURES: We defined erectile dysfunction (ED) as MPCC < 20 mm and carried out multivariate analysis using logistic regression analysis to clarify the predictors for ED, with the variables including age, the SHIM score, and the EHS. We compared the tendency for MPCC ≥ 20 mm when EHS was 3 or more with that when EHS was 2 or less. RESULTS: The median age of the patients was 59.5 years (range 18-83). In logistic regression analysis, the EHS was the only predictor for ED with MPCC < 20 mm. The mean EHS in the MPCC < 20 mm group was 1.64 ± 0.20 (mean ± SEM) and that in the MPCC ≥ 20 mm group was 2.46 ± 0.13 (P = 0.0018). There was a correlation between the EHS and the MPCC (correlation coefficient = 0.33). In comparison with the group having an EHS of 2 or less, that with an EHS of 3 or more tended to have MPCC ≥ 20 mm (P = 0.013). CONCLUSIONS: The EHS was correlated with the MPCC. The EHS represents the objective erectile function shown by the measurement of NPT.

[Clinical features of six patients with pancreas metastasis from renal cell carcinoma].

We retrospectively reviewed patients who underwent radical or partial nephrectomy and were followed up in Oji General Hospital from 1992 through 2012. A total of 6 patients had disease recurrence in the pancreas during follow-up. We investigated their clinical features and treatment outcomes. The median age at diagnosis was 75 years. The median interval from nephrectomy to the detection of pancreatic metastasis was 114 months. As local therapy for metastasis, surgical resection was selected for 4 patients. On the other hand, administration of medication, including interferon alpha and sunitinib was selected for 2 patients with other simultaneous metastatic sites. One of the 4 patients with surgical resection had disease recurrence in the residual pancreas and needed additional excision. At the median follow-up of 38 months after treatment of pancreatic metastasis, one patient remained alive without evidence of disease, 3 patients were alive with recurrent disease, and 2 patients had died of the disease.

[Rhabdomyolysis after radical nephrectomy in the lateral decubitus position: report of 2 cases].

Rhabdomyolysis is a rare perioperative complication, however, potentially lead to fatal outcome. We experienced 2 cases of rhabdomyolysis after radical nephrectomy and nephroureterectomy in the lateral decubitus position. (Case 1) A 40-years old man was seen in our hospital because of asymptomatic grosshematuria. Computed tomography revealed right renal pelvic cancer, cT3N0M0. Right radical nephroureterectomy, lymph node dissection, partial cystectomy was underwent, and the operation was finished without any trouble. At the post-operative day 1, serum creatinine level was elevated to the point of 4.2 mg/dl, and serum creatine kinase was 1,945 IU/l. Continuous hemodiafiltration (CHDF) was done at intensive-care unit (ICU), and serum creatinine and creatine kinase level were decreased. At the post-operative day 1, urine myoglobin level was prominently elevated (2,943.7 ng/ml), so we diagnosed acute renal failure due to rhabdomyolysis. (Case 2) A 40-years old man was incidentally pointed out of right renal tumor that was seen as renal cell carcinoma, cT1aN0M0. Open partial nephrectomy was underwent, and there was no trouble during the operation. After recovering from anesthesia, the patient felt left thigh pain strongly. Serum creatine kinase was 888 IU/L after the operation. At the postoperative day 1, serum creatine kinase level was markedly increased (31,138 IU/L). Serum creatinine level was 1.34 mg/dl. Urine and serum myoglobin level was prominently elevated (89,000 ng/ml and 8,634 ng/ml, respectively). We diagnosed it rhabdomyolysis, and he received large amount of fluid intravenously at intensive-care unit. Serum creatine kinase was peak out at the post-operative day 3 (20,709 IU/L), and hemodialysis was not performed.

[Treatment of hemodialyzed patient by targeted therapy in metastatic renal cell carcinoma: a case report].

Experience with treatment of hemodialyzed patients by targeted therapy is limited to the few cases reported. Little information has been provided on the safety and toxicity profile of temsirolimus and sorafenib when administered in hemodialyed patients with renal cell carcinoma (RCC). Herein, we report an RCC patient undergoing hemodialysis treated with temsirolimus and sorafenib for 16 months. The patient was a 69-year-old man who was diagnosed with right RCC. He underwent nephrectomy for a pT1b tumor in December 2002. Hemodialysis was introduced in July 2003 (7 months after nephrectomy). Seven years later, CT showed retroperitoneal nodal metastases. He was started on temsirolimus. Although 8 cycles of this therapy were done, we discontinued it because of progressive disease. The CTCAE (Common Terminology Criteria for Adverse Events) grade 3 adverse events were thrombopenia, but no adverse events of grade 4 or greater developed. Secondly, he was started on sorafenib. CT showed a partial response with a 45% decrease in tumor bulk using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. He has partial response for 13 months. He presented high blood pressure requiring pharmacological treatment, but no adverse events of grade 4 or greater developed. Patients with terminal renal failure can be offered temsirolimus and sorafenib treatment with close clinical and laboratory monitoring. Treatment of RCC patient undergoing hemodialysis by targeted therapy appears to be feasible and effective.

[Intrascrotal malignant mesothelioma diagnosed after surgery for hydrocele testis: a case report].

We report here a case of intrascrotal malignant mesothelioma, arising from the tunica vaginalis, which was diagnosed after surgery for hydrocele testis. A 52-year-old man underwent left hydrocelectomy for hydrocele testis. After pathological diagnosis as malignant mesothelioma from the specimen of tunica vaginalis, left radical orchiectomy was performed. The patient had no exposure to asbestos and there has been no evidence of recurrence.

Detection of vitellogenin incorporation into zebrafish oocytes by FITC fluorescence.

BACKGROUND: Large volumes of lymph can be collected from the eye-sacs of bubble-eye goldfish. We attempted to induce vitellogenin (Vtg) in the eye-sac lymph of bubble-eye goldfish and develop a method for visualizing Vtg incorporation by zebrafish oocytes using FITC-labeling. METHODS: Estrogen efficiently induced Vtg in the eye-sac lymph of goldfish. After FITC-labeled Vtg was prepared, it was injected into mature female zebrafish. RESULTS: Incorporation of FITC-labeled Vtg by zebrafish oocytes was detected in in vivo and in vitro experiments. The embryos obtained from zebrafish females injected with FITC-labeled Vtg emitted FITC fluorescence from the yolk sac and developed normally. CONCLUSION: This method for achieving Vtg incorporation by zebrafish oocytes could be useful in experiments related to the development and endocrinology of zebrafish oocytes.

Which Happens Earlier, Lower Urinary Tract Symptoms or Erectile Dysfunction?

INTRODUCTION: Although an association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) has been suggested, it was not clarified whether LUTS developed before ED or vice versa. AIM: To clarify whether LUTS develop before ED or vice versa and which symptoms predicted the onset of the other condition in a longitudinal community-based study. METHODS: We conducted a longitudinal community-based study on LUTS and ED in aged Japanese men. A follow-up study was conducted to determine their longitudinal changes of LUTS and ED after 15 years. Erectile function was evaluated using a validated questionnaire. LUTS were evaluated based on the International Prostate Symptom Score, quality of life index, and prostate volume. MAIN OUTCOME MEASURE: We evaluated the baseline symptoms among the participants who had LUTS and ED in the follow-up survey and what prior symptoms could predict the onset of the other condition using the data from a long-term longitudinal survey. RESULTS: A total of 108 men were enrolled in this study. Of the 47 men having both LUTS and ED in the follow-up study, men having only LUTS (n = 16) were more frequent than those having only ED (n = 6) in the initial study. Likewise, of the 38 men having both nocturia and ED at the time of the follow-up study, those having only nocturia (n = 12) were more frequent than those having only ED (n = 5) in the initial study. In multivariable analysis, age 60 years or older (odds ratio: 7.10, 95% CI: 2.09-24.13) and nocturia (odds ratio: 15.83, 95% CI: 3.05-82.15) were independent predictors for the onset of ED. CONCLUSION: There were more men with prior onset of LUTS, especially nocturia, than men with prior onset of ED among those with both ED and LUTS in this long-term longitudinal study. Nocturia may be a predictor of subsequent ED. Matsuda Y, Kobayashi K, Fukuta F, et al. Which Happens Earlier, Lower Urinary Tract Symptoms or Erectile Dysfunction?. J Sex Med 2021;9:100275.

Formation of α clusters in dilute neutron-rich matter.

The surface of neutron-rich heavy nuclei, with a neutron skin created by excess neutrons, provides an important terrestrial model system to study dilute neutron-rich matter. By using quasi-free α cluster-knockout reactions, we obtained direct experimental evidence for the formation of α clusters at the surface of neutron-rich tin isotopes. The observed monotonous decrease of the reaction cross sections with increasing mass number, in excellent agreement with the theoretical prediction, implies a tight interplay between α-cluster formation and the neutron skin. This result, in turn, calls for a revision of the correlation between the neutron-skin thickness and the density dependence of the symmetry energy, which is essential for understanding neutron stars. Our result also provides a natural explanation for the origin of α particles in α decay.

[A case of extramedullary plasmacytoma of testis converted to multiple myeloma].

A 55-year-old male was referred to our hospital with the chief complaint of painless right scrotal swelling. Serum tumor marker levels were all within the normal range. A right radical orchiectomy was performed and the histopathological diagnosis was plasmacytoma. Chest and abdominal computed tomographic scan and bone scintigraphy did not show metastasis. Serum and urine protein electrophoresis and bone marrow biopsy were negative. Diagnosis was primary testicular plasmacytoma (extramedullary plasmacytoma). Eleven months after the operation, multiple bone lesions appeared and our diagnosis was conversion to multiple myeloma.

[Clinical features of patients with brain metastasis from testicular germ cell tumor].

We retrospectively reviewed 190 patients with germ cell tumors of testis or extragonadal origin who were treated in our hospital between 1980 and 2007. Five (2.6%) of them had brain metastasis. We studied the clinical features and treatment outcome of these patients. Median age was 30 years old (23-48). The clinical stage was III in all the patients, except one with stage I disease. Two patients had brain metastasis at the initial presentation. All patients underwent multiple regimens of chemotherapy. As local therapies for brain metastases, surgical resection was done in 4 and gamma knife was in 1. Whole brain irradiation was added to surgery in 2 patients. All patients died of the disease within one year after brain metastasis development, except 1 patient who was free of disease 47 months after the presentation. The long survivor had solitary brain metastasis at the initial presentation and received 4 regimens of chemotherapy, 2 surgical resections of brain metastases and whole brain irradiation. Finally, chemotherapy consisting of irinotecan and nedaplatin resulted in normalization of the tumor markers and complete remission was proved by the subsequent surgical resection. Although most patients with brain metastasis have a poor clinical outcome, aggressive local treatment and employment of novel anticancerous agents may contribute to improve clinical course of selected patients with germ cell tumors and brain metastasis.

Fragment-Based Discovery of Novel Non-Hydroxamate LpxC Inhibitors with Antibacterial Activity.

UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is a zinc metalloenzyme that catalyzes the first committed step in the biosynthesis of Lipid A, an essential component of the cell envelope of Gram-negative bacteria. The most advanced, disclosed LpxC inhibitors showing antibacterial activity coordinate zinc through a hydroxamate moiety with concerns about binding to other metalloenzymes. Here, we describe the discovery, optimization, and efficacy of two series of compounds derived from fragments with differing modes of zinc chelation. A series was evolved from a fragment where a glycine moiety complexes zinc, which achieved low nanomolar potency in an enzyme functional assay but poor antibacterial activity on cell cultures. A second series was based on a fragment that chelated zinc through an imidazole moiety. Structure-guided design led to a 2-(1S-hydroxyethyl)-imidazole derivative exhibiting low nanomolar inhibition of LpxC and a minimum inhibitory concentration (MIC) of 4 µg/mL against Pseudomonas aeruginosa, which is little affected by the presence of albumin.

First total synthesis of trimeric indole alkaloid, psychotrimine.

The first total synthesis of (+/-)-psychotrimine, a novel trimeric indole alkaloid isolated from Psychotria rostrata, was achieved. In the total synthesis, the copper-mediated intramolecular and intermolecular aminations of halobenzenes, which respectively contributed to the construction of a pyrrolidinoindoline core and the installation of a third tryptamine unit, were used as key steps.

[VESICOVAGINAL FISTULA CAUSED BY CYSTOCELE: A CASE REPORT].

Typical etiologies of vesicovaginal fistula (VVF) include obstructed labor, iatrogenic surgical injury, pelvic irradiation and cancer invasion. VVF caused by cystocele are very rare. To date, there are no documented cases in Japanese literature.A 74-year-old woman presented with near total incontinence. On physical examination, she was found to have severe cystocele and pressure necrosis of anterior vaginal wall, which caused partial breakdown of vaginal mucosa and VVF. She underwent vesicovaginal fistula repair using transvaginal and transabdominal approaches. Catheter drainage was performed for 10 days and postoperative cystogram showed no sign of leakage. She is currently symptom-free at 55 months.

[LONGITUDINAL CHANGES OF FREE TESTOSTERONE LEVELS AND SEXUAL FUNCTION IN JAPANESE MEN EVALUATING TWO CROSS-SECTIONAL COMMUNITY-BASED STUDIES].

(Purpose) We conducted cross-sectional studies two times, in 1992 and 2007 and investigated the longitudinal changes of fT levels and sexual function by comparing the results. (Methods) In 1992 and 2007, we conducted cross-sectional surveys about lower urinary tract symptoms and sexual function in male inhabitants aged 40 to 79 years in Shimakaki village, Hokkaido. Comparing the results of these surveys, we analyzed longitudinal changes in fT levels and sexual function. FT levels were measured by radioimmunoassay and sexual function was evaluated using a validated questionnaire. (Results) A total of 123 inhabitants participated in the both surveys. The average age at the initial survey was 57.2 years.Complications causing sexual dysfunction were observed in 43 participants (35%) and 75 participants (61%) in the first and second surveys, respectively. Average fT levels were 12.9 pg/ml and 4.4 pg/ml in the first and second surveys, respectively. Linear approximations of fT (Y) using age (X) were Y = -0.12 X+19.6 and Y = -0.10 X+11.6, for the first and second surveys, respectively. Although decreased fT levels with aging were comparable in both surveys, fT levels were lower in the second survey than in the first survey. There was no significant association between fT levels and sexual function. (Conclusions) The fT levels at the time of the second surey were lower than those in the first survey. The fT level has no significant association with sexual function.

Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats.

INTRODUCTION: Intravenous preload (delivered before cavernous nerve [CN] injury) of bone marrow-derived mesenchymal stem cells (MSCs) can prevent or decrease postoperative erectile dysfunction (J Sex Med 2015;12:1713-1721). In the present study, the potential therapeutic effects of intravenously administered MSCs on postoperative erectile dysfunction were evaluated in a rat model of CN injury. METHODS: Male Sprague-Dawley rats were randomized into 2 groups after electric CN injury. Intravenous infusion of bone marrow-derived MSCs (1.0 × 106 cells in Dulbecco's modified Eagle's medium 1 mL) or vehicle (Dulbecco's modified Eagle's medium 1 mL) was performed 3 hours after electrocautery-induced CN injury. MAIN OUTCOME MEASURES: To assess erectile function, we measured intracavernous pressure at 4 weeks after MSC or vehicle infusion. Histologic examinations were performed to investigate neuronal innervation and inhibition of smooth muscle atrophy. Green fluorescent protein-positive bone marrow-derived MSCs were used for cell tracking. To investigate mRNA expression levels of neurotrophins in the major pelvic ganglia (MPGs), quantitative real-time polymerase chain reaction was performed. RESULTS: The decrease of intracavernous pressure corrected for arterial pressure and area under the curve of intracavernous pressure in the bone marrow-derived MSC group was significantly lower than that in the vehicle group at 4 weeks after infusion (P < .05). Retrograde neuronal tracing indicated that the MSC group had a larger number of FluoroGold-positive neurons in the MPGs compared with the vehicle group. The ratio of smooth muscle to collagen in the MSC group was significantly higher than in the vehicle group. Green fluorescent protein-positive bone marrow-derived MSCs were detected in the MPGs and injured CNs using confocal microscopy, indicating homing of cells to the MPGs and injured CNs. Brain-derived neurotrophic factor and glial cell-derived neurotrophic factor expression levels in the MPGs were significantly higher in the MSC group than in the vehicle group (P < .01). CONCLUSION: Intravenous infusion of bone marrow-derived MSCs after CN injury might have therapeutic efficacy in experimental erectile dysfunction. Matsuda Y, Sasaki M, Kataoka-Sasaki Y, et al. Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats. Sex Med 2018;6:49-57.