Erectile dysfunction in young patients and elderly patients by sexual encounter profile: A comparative study.

OBJECTIVE: Demand for erectile dysfunction treatments has increased not only in elderly patients but also in young patients. Reports indicate that frequent causes of erectile dysfunction in Japan are organic disorders in elderly patients and psychogenetic disorders in young patients. METHODS: We defined patients under the age of 40 as young erectile dysfunction patients, and those over 65 as elderly erectile dysfunction patients. We divided these two groups and conducted a retrospective comparative study based on medical questionnaires. We selected 215 cases of patients under the age of 40, and 176 cases of patients over the age of 65, and created a group of young patients and a group of elderly patients. We implemented the erectile hardness score, Sexual Health Inventory for Men, and sexual encounter profile questions 2 and 3 as the patient's daily clinical journal. RESULTS: The median age of young patients was 36 years, and that of elderly patients was 70 years. With respect to Sexual Health Inventory for Men, the average score was a significantly higher score in the young patients (9.26 vs 7.10, P < 0.001). Concerning erectile hardness score, young patients showed significantly higher scores in erectile hardness score (3.15 vs 2.06, P < 0.001). In terms of sexual encounter profile question 2, 50.9% of young patients responded "yes," but 24.3% of elderly patients responded, thus indicating a significantly higher score in young patients. In terms of sexual encounter profile question 3, 6.1% of young patients responded "yes," and 0.7% of elderly patients responded "yes," indicating a significantly higher in young patients. CONCLUSIONS: The results showed that many young patients with erectile dysfunction were able to perform insertion, but were unable to maintain erection.

[EFFICACY AND SAFETY OF 25 AND 50 µg DESMOPRESSIN ORALLY DISINTEGRATING TABLETS IN NOCTURIA DUE TO NOCTURNAL POLYURIA IN JAPANESE MALE PATIENTS].

(Purpose) To conduct a prospective study on the efficacy and safety of desmopressin for nocturnal polyuria. (Materials and methods) We selected 51 Japanese men, aged ≥50 years, with complaints of nocturia and a nocturnal polyuria index of ≥0.33. We administered 25 or 50 µg desmopressin (Minirinmelt Orally Disintegrating Tablet®), once daily at bedtime. We evaluated the nighttime urinary frequency and urine volume, nocturnal polyuria index, time to the first urination after falling asleep, and International Prostate Symptom Score (IPSS) at baseline and at 4, 8, and 12 weeks after administration. In addition, they underwent clinical examinations and blood tests at 1, 4, and 12 weeks to evaluate the safety of the drug. (Results) We observed a decrease in the nighttime urinary frequency and urine volume, and nocturnal polyuria index, increased prolonged time to the first urination after falling asleep, and improved IPSS at and after 4 weeks, compared to baseline data. Furthermore, the drug remained effective even at 12 weeks for all parameters. We observed adverse events in 31.3% of the patients. The incidence of hyponatraemia was particularly high in 15.7% of the patients. Those with a lower serum sodium level and lesser body weight at baseline were more likely to develop hyponatraemia. (Conclusion) Desmopressin was identified as a potential drug for the treatment of nocturnal polyuria. However, hyponatraemia, an important adverse event, resulted in treatment discontinuation in several patients. A sodium level lower than the normal level and low body weight at baseline were the risk factors for hyponatraemia.

[INITIAL TREATMENT OF NOCTURIA CAUSED BY NOCTURNAL POLYURIA WITH LOW-DOSE DESMOPRESSIN].

(Objective) Nocturia, an important male lower urinary tract symptom (LUTS), is often difficult to treat. Herein, we report our experience of the initial treatment of nocturia with the novel drug desmopressin. (Subjects and methods) Subjects included 25 patients with LUTS treated with desmopressin who had the chief complaint of nocturia. Before treatment, the frequency of nocturnal urination (≥2) and nocturnal polyuria index (≥0.33) were confirmed based on the urination diary for ≥ 72 h. Before sleep, 25 or 50 mg desmopressin (Minirin® Melt OD tablets) was administered once daily. The frequency of nocturnal urination, volume of nocturnal urine, time from falling asleep to first urination, first urinary volume after falling asleep, nocturnal polyuria index, International Prostate Symptom Score (IPSS), quality of life index, Overactive Bladder Symptom Score, and residual urine volume were comparatively evaluated before and 4 weeks after treatment. Treatment effect was self-evaluated by patients 4 weeks after the treatment. Safety was evaluated by interview and blood testing 1 and 4 weeks after the treatment. (Results) Decrease in the frequency of nocturnal urination and improvement in IPSS were observed. According to self-evaluation of the treatment, 72.6% of the patients considered the treatment efficacious. Regarding safety, adverse events were observed in 28% of the patients, particularly hyponatremia (12% of the patients). (Conclusion) Desmopressin is a potential key drug for the treatment of nocturia caused by nocturnal polyuria.

Lipid abnormality, current diabetes and age affect erectile hardness: An analysis of data from complete medical checkups carried out at a single hospital.

OBJECTIVES: To investigate the correlation between the Erection Hardness Score and both erectile function and metabolic and lifestyle factors. METHODS: This study included 548 men who underwent a complete standard medical checkup at Yokohama Shin-midori General Hospital between 1 July 2016 and 31 August 2018, and answered the question about erectile hardness. The following variables were evaluated: age, erectile hardness on the Erection Hardness Score, erectile function on the Sexual Health Inventory for Men, current medical history (diabetes, hypertension, dyslipidemia, heart disease, stroke), metabolic risk factors (abdominal circumference, hyperglycemia, high blood pressure, lipid abnormality) and lifestyle factors. First, to examine the correlation between erectile hardness and erectile function, the mean Sexual Health Inventory for Men score by Erection Hardness Score grade was determined for each age group. Then, an analysis was carried out to examine the association between erectile hardness and age, current medical history, metabolic risk factors, and lifestyle factors. RESULTS: In each age group, a lower Erection Hardness Score grade was associated with a lower mean Sexual Health Inventory for Men score. Lipid abnormality, diabetes and age were independent risk factors for decreased erectile hardness. CONCLUSIONS: Erection Hardness Score is a useful tool that can easily and accurately assess erectile function in the settings of medical checkups and clinical practice. Diabetes and lipid abnormality affect erectile hardness.

[EFFECTIVENESS AND SAFETY OF TADALAFIL IN VERY ELDERLY PATIENTS WITH LOWER URINARY TRACT SYMPTOMS].

(Aim) The α-1 blockers have been used as first-line therapy for benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS). A new phosphodiesterase type 5 inhibitor, tadalafil, was approved in 2014 and received a Grade A recommendation in the 2017 clinical practice guidelines for LUTS. In this study, we examined the effectiveness and safety of tadalafil in very elderly patients with LUTS. (Subjects and methods) The subjects were 84 very elderly patients, at least 75 years of age, with BPH/LUTS for which they had been administered tadalafil.Data of the 71 patients were retrospectively reviewed in terms of the International Prostate Symptom Score (IPSS), quality of life (QOL) index, overactive bladder symptom score (OABSS), maximum flow rate and postvoid residual urine volume at baseline and at weeks 4, 8, 12, and 24. We also examined the safety of tadalafil therapy. (Results) Patient characteristics were: median age 80.1±4.38 years, prostate volume 41.2±24.3 cc and IPSS 15.7±5.68. Patients who had undergone treatment for BPH/LUTS prior to tadalafil therapy accounted for 67.9% of the study population.Significant improvements occurred in IPSS, QOL and OABSS at week 4, and the improvements were maintained until week 24. As for postvoid residual urine test results, a significant improvement was seen at week 8 only.Adverse events were noted in 9 patients (10.7%), but only 5 (6.0%) needed to discontinue tadalafil therapy. (Conclusion) Tadalafil is considered to be a highly effective and safe drug in very elderly patients with LUTS.

[A Study of the Efficacy of the Additional Administration of Tadalafil in Japanese Men with α1-Blocker-Resistant LUTS/BPH].

Alpha 1-blockers are widely used at present for lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). However, some patients experience little improvement of symptoms, and it is difficult to provide additional treatment. We have additionally administered tadalafil to patients with inadequate symptom improvement, despite treatment with alpha-1 blockers. The subjects were 57 patients with a diagnosis of LUTS/BPH who showed a poor response to treatment with alpha-1 blockers for 1 month or more (international prostate symptom score [IPSS] ≥8 and/or quality of life [QOL] index ≥3). Tadalafil 5 mg was administered on consecutive days to patients orally receiving alpha-1 blockers. We determined IPSS, the QOL index, overactive bladder symptom scores (OABSS), maximum urine flow, residual urine volume, and the sexual health inventory for men (SHIM) before, and 4, 8, and 12 weeks after administration, and then evaluated improvement effects. IPSS, the QOL index, OABSS, and SHIM showed significant improvement (P ＜0.05) at 4 weeks after the start of treatment and onward. IPSS and the QOL index showed greater improvement effects at 8 and 12 weeks. Residual urinary volume was significantly improved only at 8 weeks. However, the maximum urine flow showed no improvement at any time point. Our results demonstrated the additional administration of tadalafil to patients with LUTS showing poor responses to alpha-1 blockers to improve LUTS/BPH symptoms as well as sexual function.

Fluvoxamine, an anti-depressant, inhibits human glioblastoma invasion by disrupting actin polymerization.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor with a median survival time about one year. Invasion of GBM cells into normal brain is the major cause of poor prognosis and requires dynamic reorganization of the actin cytoskeleton, which includes lamellipodial protrusions, focal adhesions, and stress fibers at the leading edge of GBM. Therefore, we hypothesized that inhibitors of actin polymerization can suppress GBM migration and invasion. First, we adopted a drug repositioning system for screening with a pyrene-actin-based actin polymerization assay and identified fluvoxamine, a clinically used antidepressant. Fluvoxamine, selective serotonin reuptake inhibitor, was a potent inhibitor of actin polymerization and confirmed as drug penetration through the blood-brain barrier (BBB) and accumulation of whole brain including brain tumor with no drug toxicity. Fluvoxamine inhibited serum-induced ruffle formation, cell migration, and invasion of human GBM and glioma stem cells in vitro by suppressing both FAK and Akt/mammalian target of rapamycin signaling. Daily treatment of athymic mice bearing human glioma-initiating cells with fluvoxamine blocked tumor cell invasion and prolonged the survival with almost same dose of anti-depressant effect. In conclusion, fluvoxamine is a promising anti-invasive treatment against GBM with reliable approach.

EFFECT OF TADALAFIL THAT WAS ADDITIONALLY ADMINISTERED TO PATIENTS RECEIVING AN ALPHA1-BLOCKER IN JAPANESE MEN WITH LOWER URINARY TRACT SYMPTOMS SUGGESTIVE OF BENIGN PROSTATIC HYPERPLASIA.

(Objectives) Alpha1-blockers have been widely used for the treatment of lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). As improvement of symptoms occur relatively early after the administration of alpha-1 blockers, the blockers are considered to be extremely beneficial. However, some patients respond poorly to the blockers, providing additional treatment is difficult. Here we examined the efficacy of tadalafil that was additionally administered to patients receiving an oral alpha-1 blocker. (Subjects and methods) The subjects were patients who had been diagnosed with BPH/LUTS, had received an oral alpha1-blocker for at least 1 month, and had responded poorly to the alpha-1 blocker treatment (International Prostate Symptom Score IPSS ≥8 and/or QOL index ≥3). Tadalafil 5 mg was administered on consecutive days to patients orally receiving an alpha-1 blocker. The following were measured before and at 4 and 8 weeks after the administration of tadalafil to evaluate the add-on effect of Tadalafil: IPSS, QOL index, Overactive Bladder Symptom Score (OABSS), maximal urinary flow rate, residual urine volume, and International Index of Erectile Function-5 (IIEF-5). (Results) We studied 41 patients until 8 weeks after the drug administration. Tadalafil produced significant improvement in IPSS, QOL index, OABSS, and IIEF-5 at 4 weeks after the administration, as compared with before administration (P < 0.05). The improvement was even more significant at 8 weeks. However, the maximal urinary flow rate or residual urine volume did not differ significantly at any time point. (Conclusions) The results of this study revealed that additional administration of tadalafil improves not only urinary conditions but also sexual function in patients with BPH/LUTS.

INITIAL EXPERIENCE OF THE ENZALUTAMIDE TREATMENT FOR CASTRATION-RESISTANT PROSTATE CANCER.

(Objective) Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with castration-resistant prostate cancer (CRPC). We retrospectively evaluated clinical efficacy and safety of enzalutamide in CRPC. (Patients and methods) We reviewed clinical records of 73 patients who had received enzalutamide for the CRPC at Showa University and affiliated 7 hospitals. Enzalutamide was given at a dose of 160 mg/day, but some patients were treated at lower dose because of there age or poor performance status. Prostrate-specific antigen (PSA) response, prior docetaxel use and the previously administered agents were evaluated retrospectively. (Results) The median patients age was 77 years, the median Gleason score was 9 and the median PSA level at baseline was 26.9 ng/ml. The patients who had prior docetaxel use were 29 (39.7%) and the median of total docetaxel dose was 460 mg/body. The median number of total prior treatments (anti-androgens, Estramustine and steroid) was 3. Twenty seven (61.4%) patients with docetaxel-naïve achieved over 50% reduction of PSA level from baseline, but only 7 (24.1%) in patients previously treated with docetaxel. The most common adverse events included fatigue (24.7%), anorexia (24.7%) and the nausea (16.4%). We found a small proportion of responders to enzalutamide experienced a PSA flare. (Conclusion) Our results of the use of Enzaltamide for CRPC were similar with previous reports. PSA flare was found in some patients with CRPC who responded to enzaltamide. It should be noted that this possible PSA flare phenomenon.

[Testicular tumor with opposite inguinal lymph node metastasis in a patient with prior orchiopexy for undescended testis].

The patient was a 54-year-old man. At age 6 years, he had undergone orchiopexy for left undescended testis. Six months prior to the current presentation, he visited our hospital with a chief complaint of painless enlargement of the left testis. Left high orchiectomy was performed under a diagnosis of left testicular tumor. Histopathological examination determined the tumor to be a seminoma (pT2). Postoperatively, the patient was placed on surveillance without preventive radiation treatment. He visited our hospital six months after surgery due to a painless mass in the right inguinal region. All tumor markers (AFP, HCG-ß, and LDH) were within normal ranges. However, based on ultrasound and CT scan findings, lymph node metastasis was suspected and a right inguinal lymph node excision was thus performed. Histopathological examination led to the diagnosis of seminoma.

Inhalation of 10% carbon dioxide rapidly terminates Scn1a mutation-related hyperthermia-induced seizures.

The aim of this study was to assess the anticonvulsant effect of carbon dioxide (CO2) on Scn1a mutation-related febrile seizures. We examined physiological changes in the blood gas levels after the induction of hyperthermia-induced seizures (HISs), which were associated with the Scn1a missense mutation. We determined the efficacy of inhalation of 5% or 10% CO2 to treat HISs. HISs were evoked in Scn1a mutant and wild-type (WT) rats by hot water baths. To determine the anticonvulsant effect of CO2 inhalation, rats were placed in a chamber filled with air or mixed gas containing 5% CO2 or 10% CO2 for 3 min, immediately after the induction of HISs. We also analyzed the blood gas levels at the end of inhalation of CO2. Hot water bathing induced a significant reduction in the partial pressure of CO2 (pCO2) and respiratory alkalosis in the WT and Scn1a mutant rats. HISs were evoked in 100% of the Scn1a mutant rats within 5 min, but in none of the WT rats. The Scn1a mutant rats demonstrated a higher HISs susceptibility associated with respiratory alkalosis than the WT rats. Inhalation of 10% CO2 shortened the seizure duration from 62.6±12.1 s to 15.5±1.0 s. Blood gas analysis after the inhalation of 10% CO2 demonstrated an elevated pCO2 level and respiratory acidosis. Inhalation of 10% CO2 demonstrated a potent and fast-acting anticonvulsant effect against HISs.

High-frequency EEG oscillations in hyperthermia-induced seizures of Scn1a mutant rats.

We examined high-frequency oscillations (HFOs) in the ictal cortical EEGs of hyperthermia-induced seizures in a rat model of febrile seizures with an SCN1A mutation as a means of investigating the pathophysiological mechanisms underlying the generation of febrile seizures. We used 13 male homozygous Scn1a-N1417H mutant rats (F344/NSlc-Scn1a(Kyo811)) and 10 wild-type control rats. Generalized tonic-clonic seizures were induced in all mutant rats, and HFOs with frequencies ranging from 200 to 400 Hz were found to precede spikes during the clonic phases of these seizures in the ictal EEGs. The proportion of all spikes in each seizure that were associated with HFOs increased with age. In time-frequency spectra of the EEG data, the HFOs had a mean peak frequency of 301.1 ± 65.4 Hz (range: 156.3-468.8Hz) and a mean peak power of 24.6 ± 3.8 dB (range: 11.4-33.4 dB); the peak power increased with age. Regarding the wild-type rats, a brief seizure without unmistakable HFOs was exceptionally induced in only one rat. The generation mechanism of febrile seizures is still an unanswered question. The detection of HFOs from the ictal EEGs of hyperthermia-induced seizures may provide a cue to answering this open question, although in this research we were unable to provide sufficient evidence to prove that the generation of HFOs depended on the mutation.

[A case of vesical endometriosis that worsened during the early pregnancy period].

We report a case of vesical endometriosis that worsened during the early pregnancy period. A 37-year old woman had been under treatment for endometriosis (including vesical endometriosis) by a gynecologist during the past 10 years. She was treated for sterility 1 year ago, and became pregnant through in vitro fertilization. In her 8th gestational week, she complained of gross hematuria at our hospital. Cystoscopic findings revealed some tumors that appeared worse than the last findings two years ago. In order to deny malignancy, transurethral resection of the bladder tumor was performed in her 12th gestational week. The pathologic diagnosis was endometriosis. She was able to stay pregnant, and delivered a girl. After delivery, cystoscopic findings revealed reduction of tumors. In most cases pregnancy cures endometriosis ; however, in this case symptoms became worse during the early stage of pregnancy. The reason for this contrary event is discussed.

Combining poly-arginine with the hydrophobic counter-anion 4-(1-pyrenyl)-butyric acid for protein transduction in transdermal delivery.

Topical therapy is the most favored form of treatment for whitening against hyperpigmentation and sunburn because it lends itself to self-administration, patient compliance, and absence of systemic adverse effects. However, transdermal delivery of hydrophilic chemicals is difficult. The main purpose of this study is to develop a delivering system of hydrophilic drugs and proteins across the skin. Hydroquinone (HQ), a well-known tyrosinase inhibitor and antimelanogenesis compound, and enhanced green fluorescent protein (EGFP) were fused with eleven poly-arginine (11R). Both HQ-11R and EGFP-11R were efficiently delivered in B16 cells, a mouse melanoma cell line. HQ-11R was as effective as HQ alone at inhibiting melanin synthesis in B16 cells. EGFP-11R was efficiently delivered into cells of the epidermis with 4-(1-pyrenyl)-butyric acid (PB), a counteranion bearing an aromatic hydrophobic moiety, in vivo, but EGFP alone or EGFP-11R without PB was not. Finally, topical application of HQ-11R with PB significantly inhibited UV irradiation-induced pigmentation in guinea pigs compared with HQ alone. These results suggest that topical therapy using poly-arginine in combination with PB is useful for the delivery of hydrophilic drugs and proteins by the transdermal route.

Therapy for hyperthermia-induced seizures in Scn1a mutant rats.

PURPOSE: Mutations in the SCN1A gene, which encodes the α1 subunit of voltage-gated sodium channels, cause generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). N1417H-Scn1a mutant rats are considered to be an animal model of human FS+ or GEFS+. To assess the pharmacologic validity of this model, we compared the efficacies of eight different antiepileptic drugs (AEDs) for the treatment of hyperthermia-induced seizures using N1417H-Scn1a mutant rats. METHODS: AEDs used in this study included valproate, carbamazepine (CBZ), phenobarbital, gabapentin, acetazolamide, diazepam (DZP), topiramate, and potassium bromide (KBr). The effects of these AEDs were evaluated using the hot water model, which is a model of experimental FS. Five-week-old rats were pretreated with each AED and immersed in water at 45°C to induce hyperthermia-induced seizures. The seizure manifestations and video-electroencephalographic recordings were evaluated. Furthermore, the effects of each AED on motor coordination and balance were assessed using the balance-beam test. KEY FINDINGS: KBr significantly reduced seizure durations, and its anticonvulsant effects were comparable to those of DZP. On the other hand, CBZ decreased the seizure threshold. In addition, DZP and not KBr showed significant impairment in motor coordination and balance. SIGNIFICANCE: DZP and KBr showed potent inhibitory effects against hyperthermia-induced seizures in the Scn1a mutant rats, whereas CBZ exhibited adverse effects. These responses to hyperthermia-induced seizures were similar to those in patients with GEFS+ and SMEI. N1417H-Scn1a mutant rats may, therefore, be useful for testing the efficacy of new AEDs against FS in GEFS+ and SMEI patients.