Okinawa Kyodo Hospital

Okinawa, Japan

Okinawa Kyodo Hospital

Okinawa, Japan
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Kadekawa K.,University of Pittsburgh | Kadekawa K.,Southern Knights Laboratory | Kadekawa K.,Okinawa Kyodo Hospital | Yoshizawa T.,University of Pittsburgh | And 7 more authors.
Experimental Neurology | Year: 2017

Purpose To examine (1) whether spinal cord injury (SCI) time-dependently increases the severity of autonomic dysreflexia (AD) and expression levels of bladder nerve growth factor (NGF) protein, and (2) whether local suppression of NGF in the bladder improves SCI-induced AD in rats. Materials and methods SCI was produced by the transection of the T2/3 spinal cord in female Sprague-Dawley rats. At 4 or 8 weeks after SCI, differences in the mean arterial blood pressure (ΔMAP) and heart rate (ΔMHR) during graded increases in intravesical pressure to 20, 40 and 60 cm H2O from those before bladder distention and NGF protein levels in the bladder wall were evaluated in spinal intact and SCI rats under urethane anesthesia. Seven weeks after SCI liposome-NGF antisense conjugates were administered intravesically to the animals. At 1 week after intravesical treatment (8 weeks after SCI), ΔMAP and ΔMHR during bladder distention and bladder NGF protein expression were evaluated. Results The ΔMAP and ΔMHR were increased in a graded manner in response to bladder distention at intravesical pressures of 20, 40 and 60 cm H2O in SCI rats. These AD-like cardiovascular responses and NGF protein expression in the bladder mucosal and muscle layers were increased after SCI in a time-dependent manner. The liposome-NGF antisense treatment significantly reduced the NGF protein overexpression in the mucosal layer of SCI rat bladder and reduced ΔMAP and ΔMHR elicited by bladder distention. Conclusions These results indicate that the duration of the post-SCI recovery period affects the severity of AD induced by bladder distention as well as the level of bladder NGF protein, and that local suppression of NGF expression in the bladder reduces SCI-induced AD. Thus, Intravesical application of liposome-NGF antisense conjugates can be a new effective therapy for bladder distention-induced AD after SCI. © 2017 Elsevier Inc.


Kadekawa K.,University of Pittsburgh | Kadekawa K.,Southern Knights Laboratory | Kadekawa K.,Okinawa Kyodo Hospital | Yoshimura N.,University of Pittsburgh | And 9 more authors.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2016

To clarify the lower urinary tract function in mice, we compared bladder and urethral activity between rats and mice with or without spinal cord injury (SCI). Female Sprague-Dawley rats and C57BL/6N mice were divided into five groups: 1) spinal intact (SI) rats, 2) SI mice, 3) pudendal nerve transection (PNT) SI mice, 4) spinal cord injury (SCI) rats, and 5) SCI mice. Continuous cystometry (CMG) and external urethral sphincter (EUS)-electromyogram (EMG) analyses were conducted under an awake, restrained condition. During voiding bladder contractions, SI animals exhibited EUS bursting with alternating active and silent periods, which, in rats but not mice, coincided with small-amplitude intravesical pressure oscillations in CMG recordings. In SI mice with bursting-like EUS activity, the duration of active periods was significantly shorter by 46% (32 ± 5 ms) compared with SI rats (59 ± 9 ms). In PNT-SI mice, there were no significant differences in any of cystometric parameters compared with SI mice. In SCI rats, fluid elimination from the urethra and the EUS bursting occurred during small-amplitude intravesical pressure oscillations. However, SCI mice did not exhibit clear EUS bursting activity or intravesical pressure oscillations but rather exhibited intermittent voiding with slow large-amplitude reductions in intravesical pressure, which occurred during periods of reduced EUS activity. These results indicate that EUS pumping activity is essential for generating efficient voiding in rats with or without spinal cord injury. However, EUS bursting activity is not required for efficient voiding in SI mice and does not reemerge in SCI mice in which inefficient voiding occurs during periods of reduced tonic EUS activity. © 2016 The American Physiological Society.


Nagata M.,Kanagawa Cancer Center | Nagata M.,Okinawa Kyodo Hospital | Ito H.,Kanagawa Cancer Center | Matsuzaki T.,Kanagawa Cancer Center | And 5 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2017

OBJECTIVES: Cachexia has been shown to be related to mortality in patients with advanced cancers and chronic obstructive pulmonary disease. Smokers receiving surgery for lung cancer are thought to be at risk of developing cachexia postoperatively. We aimed to investigate whether 2 surrogate variables for cachexia, body mass index (BMI) and C-reactive protein (CRP) level, are predictive of mortality in smokers after complete resection of non-small-cell lung cancer. METHODS: We retrospectively examined 678 patients who underwent curative lobar resection for non-small-cell lung cancer at our hospital. Associations between clinicopathological factors and overall survival were assessed in smokers (N= 421) and never smokers (N= 257). RESULTS: Multivariate analysis of the smokers group showed that preoperative BMI ≤ 20.6 kg/m2 and CRP ≥ 0.13 ng/ml were risk factors for poorer prognosis, independent of age and pathological stage. In never smokers, BMI and CRP were not significantly associated with survival. Smokers in the high-risk group, defined based on preoperative BMI and CRP, had shorter survival after recurrence, although they did not have an elevated recurrence rate. Despite the absence of recurrence, they died more frequently of pneumonia or other cancers. These observations are consistent with the idea that the poor postoperative prognosis could have resulted from the progression of cachexia. CONCLUSIONS: In smokers with non-small-cell lung cancer, preoperative low BMI and elevated CRP are predictive factors for poor prognosis after complete resection, probably as a result of cachexia progression. The effective treatment of cachexia might improve postoperative prognosis. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.


PubMed | Okinawa Kyodo Hospital, Tomishiro Central Hospital, Southern Knights Laboratory LLP, Nanbu Tokushukai Hospital and Sakumoto Urology and Dermatology Clinic
Type: Journal Article | Journal: Lower urinary tract symptoms | Year: 2016

To clarify the influence of naftopidil, an 1D/A -adrenergic receptor antagonist, on the autonomic nervous system, we examined the relation between lower urinary tract symptoms (LUTS) and the plasma monoamine levels before and after naftopidil treatment in benign prostatic hyperplasia (BPH) patients.A total of 43 patients with BPH were studied. The frequency of urination, international prostate symptom score (IPSS), quality of life (QOL) index, overactive bladder symptom score (OABSS), and plasma monoamine levels (adrenaline, noradrenaline, dopamine, and serotonin) were evaluated before and after naftopidil treatment.Naftopidil significantly improved urinary frequency in daytime and nighttime, IPSS, QOL index and OABSS in all patients, and decreased the plasma adrenaline level at 8 weeks. When the patients were divided into two groups based on the median adrenaline level (40.5 pg/mL) before treatment, urinary frequency in daytime and/or nighttime, incomplete emptying and poor flow in the IPSS, and the QOL index were significantly improved in the high adrenaline (HA) group, but not in the low adrenaline (LA) group. The pretreatment plasma serotonin level was significantly lower in the HA group than in the LA group, but it increased gradually after the start of treatment until there was no difference between the groups.The modulation of plasma adrenaline and serotonin levels by naftopidil in patients with increased sympathetic activity contributed to improvement of LUTS associated with BPH, in addition to its antagonistic effects of 1D/A -adrenergic receptor on the detrusor and prostatic urethral smooth muscle, the urothelium, and the central nervous system.


Sugaya K.,Kitakami Central Hospital | Sugaya K.,Southern Knights Laboratory LLP | Sekiguchi Y.,Yokohama Motomachi Womens Clinic LUNA | Satoh T.,Satoh Continence Clinic | And 5 more authors.
International Journal of Urology | Year: 2014

Objectives: To investigate whether the anticholinergic agent, propiverine hydrochloride, is clinically effective for stress urinary incontinence. Methods: The participants were adult female patients with the chief complaint of stress incontinence. Propiverine (20 mg once daily) was given for 8 weeks. If the response was inadequate after 4 weeks of treatment, the dose was increased to 40 mg/day. Before and after 4 and 8 weeks of treatment, lower urinary tract symptoms were assessed. The urethral pressure and blood catecholamine levels were also measured. Results: A total of 37 patients (mean age 69 ± 11 years) were enrolled, including 15 patients with stress incontinence and 22 with mixed incontinence. The number of episodes of stress incontinence decreased significantly from 2.6 ± 2.3 times per day to 1.3 ± 2.2 times per day after 4 weeks, and 0.4 ± 0.6 times per day after 8 weeks. The daytime and night-time frequency of urination, and quality of life score showed significant improvement. The maximum urethral closing pressure and the functional urethral length increased significantly after treatment, but blood catecholamine levels, blood pressure and pulse rate at 8 weeks were not significantly different from those at baseline. Conclusions: Propiverine could be an effective drug for stress urinary incontinence by increasing urethral closing pressure without increasing blood catecholamine levels. © 2014 The Japanese Urological Association.


Saji N.,Kawasaki Medical School | Saji N.,Comprehensive Care | Kimura K.,Nippon Medical School | Tateishi Y.,Nagasaki University | And 5 more authors.
Journal of Thrombosis and Thrombolysis | Year: 2016

The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2–4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin. © 2016 Springer Science+Business Media New York


PubMed | Okinawa Kyodo Hospital, Juntendo University, Jikei University School of Medicine, Kawasaki Medical School and 3 more.
Type: Journal Article | Journal: Journal of thrombosis and thrombolysis | Year: 2016

The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8% of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2%, P=0.06) and a lower risk of any ischemic events (6.0 vs. 7.6%, P=0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6%, P=0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.


Kadekawa K.,Southern Knights Laboratory LLP | Kadekawa K.,Okinawa Kyodo Hospital | Nishijima S.,Southern Knights Laboratory LLP | Ashitomi K.,Southern Knights Laboratory LLP | And 2 more authors.
International Journal of Urology | Year: 2012

Objectives: To investigate the effects of the antimuscarinic agent, propiverine, on the bladder and urethra in rats. Methods: A total of 54 female rats were given propiverine, imidafenacin (an antimuscarinic agent), or distilled water by gavage once or twice daily. After 2weeks, bladder and urethral activity were recorded under urethane anesthesia. In the propiverine group, the changes of bladder and urethral activity before and after intravenous injection of α 1-adrenergic antagonists (prazosin, silodosin and naftopidil) were also recorded. Furthermore, the leak point pressure after electrical stimulation of abdominal wall muscles was measured in rats with vaginal distension from the control and propiverine groups. Results: Intravesical baseline pressure was significantly lower in the propiverine and imidafenacin groups compared with the control group, whereas the urethral baseline pressure was significantly higher in the propiverine group compared with the control or imidafenacin groups. Intravenous injection of prazosin (an α 1-receptor antagonist) significantly decreased the urethral baseline pressure in both of the propiverine and control groups. Intravenous injection of silodosin and naftopidil (α 1A- and α 1D-receptor antagonists, respectively) significantly decreased the maximum contraction pressure and the urethral baseline pressure in the propiverine group. The leak point pressure of the propiverine group was significantly higher than that of the control group. Conclusions: An increase of catecholamines after propiverine administration might activate smooth muscle of the proximal urethra via α 1A- and α 1D-adrenergic receptors, as well as activating urethral and pelvic floor striated muscle via the spinal motoneurons. © 2012 The Japanese Urological Association.


Kadekawa K.,Southern Knights Laboratory LLP | Kadekawa K.,Okinawa Kyodo Hospital | Sugaya K.,Southern Knights Laboratory LLP | Nishijima S.,Southern Knights Laboratory LLP | And 4 more authors.
Life Sciences | Year: 2013

Aims Alpha1D-adrenoceptors (α1D-ARs) located in the spinal cord are involved in the control of lower urinary tract function. In order to clarify the effect of α1D-ARs on storage function in the spinal cord, we examined the effect of oral administration and intrathecal injection of the α1D/A-AR antagonist, naftopidil, on bladder activity, as well as the effect of naftopidil on bladder wall histology, in female rats with spinal cord injury (SCI). Main methods Adult female Sprague-Dawley rats with Th9-10 spinal cord transection were used. In SCI rats with or without 5 mg/day of naftopidil for 4 weeks, bladder activity was examined via continuous cystometry. In other SCI rats, bladder activity was examined before and after intrathecal injection of naftopidil. In addition, bladder wall histology was compared between SCI rats with or without oral administration of naftopidil for 4 weeks. Key findings Oral administration of naftopidil decreased the number of non-voiding contractions (NVCs). Intrathecal injection of naftopidil prolonged the interval between voiding contractions, decreased the maximum voiding contraction pressure and the number of NVCs, and increased bladder capacity without affecting the residual urine volume. Oral administration of naftopidil also decreased bladder wall fibrosis. Significance The α1D/A-AR antagonist naftopidil might act on the bladder and spinal cord to improve detrusor hyperreflexia in the storage state in SCI female rats. Naftopidil also suppressed bladder wall fibrosis, suggesting that it may be effective for the treatment of neurogenic lower urinary tract dysfunction after SCI. © 2013 Elsevier Inc.

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