Researchers Database

nakai hideo

    Children'sMedicalCenterTochigi,divisionofpediatricurology Professor
Last Updated :2021/12/04

Researcher Information

Research funding number

  • 50167540

J-Global ID

Research Interests

  • cryptorchidism   nocturnal enuresis   urinary incontinence   lower urinary tract dysfunction   neurogenic bladder   disorder of sexual development   hypospadia   contenital anomaly of the genital organ   congenital hydronephrosis   vesicoureteral reflux   congenital anomaly of the kidney and the urinary tract   pediatric urology   

Research Areas

  • Life sciences / Urology / pediatric urology

Academic & Professional Experience

  • 2007/09 - Today  Jichi Medical Universitydepartment of pediatric urologyprofessor
  • 2005/05 - 2007/08  Dokkyo Medical Universitydepartment of urologyassociate professor
  • 2002/05 - 2005/04  Dokkyo Medical Universitydepartment of urology講師
  • 1992/10 - 2002/04  Tokyo Metropolitan Kiyose Children's Hospitaldepartment of urology医長
  • 1991/07 - 1992/09  Mainz Universitydepartment of urology研究生
  • 1987/06 - 1991/06  Tokyo Metropolitan Kiyose Children's Hospitaldepartment of urology医員
  • 1986/06 - 1987/05  Keio Universitydepartment of urology助手
  • 1985/06 - 1986/05  Tokyo Metropolitan Kiyose Children's Hospitaldeoartment of urology研究生
  • 1984/06 - 1985/05  国立東京第二病院泌尿器科医員
  • 1983/06 - 1984/05  Keio Universitydepartment of urology助手
  • 1982/04 - 1983/05  東京都済生会中央病院外科医員
  • 1981/09 - 1982/03  Keio Universitydepartment of surgeryresident


  • 1975/04 - 1981/08  Keio University  School of Medicine

Published Papers

  • Taiju Hyuga, Shigeru Nakamura, Shina Kawai, Taro Kubo, Rieko Furukawa, Toshinori Aihara, Makiko Mieno, Hideo Nakai
    WORLD JOURNAL OF UROLOGY 35 (10) 1611 - 1616 0724-4983 2017/10 [Refereed][Not invited]
    Endoscopic transurethral incision (TUI) of posterior urethral valve (PUV) can improve daytime urinary incontinence (DUI) and nocturnal enuresis (NE). However, the underlying mechanism has not been elucidated. In this study, we retrospectively examined the mobility of the urethra before and after TUI by measuring the urethral angle with voiding cystourethrography (VCUG), to clarify the effects of TUI on the morphology of the urethra during voiding. Between July 2010 and December 2014, 29 boys with intractable DUI and/or NE were diagnosed as PUV and underwent endoscopic TUI. VCUG during voiding phase was performed at sequential radiographic spot images (1 image per second) at a 45A degrees angle in oblique standing position. The point at which the angle of the urethra was the smallest during urination was regarded as the minimum urethral angle. The maximum urethral angle during early voiding phase was compared with the minimum urethral angle, and the percentage by which this angle changed was calculated as the flexion rate. Then changes in minimum urethral angle and flexion rate were analyzed before and 3-4 months after TUI. After TUI, the minimum urethral angle on VCUG became more obtuse (before vs. after TUI, respectively: 112.7 vs. 124.5A degrees, p < 0.001), the flexion rate decreased (before vs. after TUI, respectively: 11.8 vs. 4.1%, p < 0.001). This study demonstrated a significant difference in the degree of change. The findings may contribute to understanding of the mechanism of improvement in symptoms after TUI in patients with PUV.
  • Taiju Hyuga, Shigeru Nakamura, Shina Kawai, Hideo Nakai
    UROLOGY 105 153 - 156 0090-4295 2017/07 [Refereed][Not invited]
    OBJECTIVE To evaluate the effectiveness of a 3-month enuresis alarm (EA) treatment and repeat EA treatment among pediatric patients with nocturnal enuresis, and to compare patient characteristics among "responders" and "nonresponders" to treatment. MATERIALS AND METHODS Clinical outcomes were retrospectively evaluated for 137 children (94 boys and 43 girls, mean age, 10.1 years). Effectiveness was evaluated after an initial 3-month treatment, using the International Children's Continence Society criteria. Among children in the no-response group at 3 months, those who continued the EA treatment for >= 4 months were subclassified into group 1, whereas children who repeated the EA treatment at an interval >= 6 months were subclassified into group 2. RESULTS Among our 137 cases, 19 achieved complete response and 47 achieved partial response at 3 months, for an overall treatment effectiveness rate of 48%. Among the no-response group, treatment was extended in 17 cases (group 1), with 3 (18%) achieving a successful outcome. Treatment was repeated in 18 cases (group 2). In group 2, 8 (44%) achieved successful outcome at 3-month time point. Daytime urinary incontinence did not modify treatment effectiveness. CONCLUSION EA treatment should be given for a short period of time and should not be continued without a definite purpose or clear response. Suspending and then repeating this treatment after an appropriate interval is effective for patients who do not respond to the initial course of treatment. (C) 2017 Published by Elsevier Inc.
  • Shina Kawai, Takahiro Kanai, Taiju Hyuga, Shigeru Nakamura, Jun Aoyagi, Takane Ito, Takashi Saito, Jun Odaka, Rieko Furukawa, Toshinori Aihara, Hideo Nakai
    PEDIATRICS INTERNATIONAL 59 (7) 781 - 785 1328-8067 2017/07 [Refereed][Not invited]
    Background: Acute-phase technetium-99 m dimercaptosuccinic acid (DMSA) scintigraphy is recommended for initial imaging in children with febrile urinary tract infection (fUTI). Recently, the importance of identifying patients at risk of recurrent fUTI (r-fUTI) has been emphasized. To clarify the effectiveness of DMSA scintigraphy for predicting r-fUTI in infants, we investigated the relationship between defects on DMSA scintigraphy and r-fUTI. Methods: Seventy-nine consecutive infants (male: female, 60:19) with fUTI were enrolled in this study. DMSA scintigraphy was performed in the acute phase, and patients with defect underwent voiding cystourethrography and chronic-phase (6 months later) DMSA scintigraphy. Patients were followed on continuous antibiotic prophylaxis (CAP). Results: Defects on acute-phase DMSA scintigraphy were observed in 32 children (40.5%) of 79. The mean follow-up observation period was 17.0 +/- 10.1 months. Four patients had r-fUTI (5%). Two of them had defects on DMSA scintigraphy in both the acute phase and chronic phase, and had bilateral vesicoureteral reflux (VUR) grade IV. Two others had r-fUTI without defects on DMSA and did not have VUR. Twelve patients had defect on chronic-phase DMSA scintigraphy and four of them had no VUR. Conclusions: The top-down approach is a possible method for predicting r-fUTI in infants and does not miss clinically significant VUR. Also, given that the prevalence of r-fUTI was 5% regardless of the presence of defects on acute-phase DMSA, then, in conjunction with genital hygiene and CAP, acute-phase DMSA might be unnecessary if chronic-phase DMSA is performed for all patients to detect renal scar.
  • Takeo Nakaya, Taiju Hyuga, Yukichi Tanaka, Shina Kawai, Hideo Nakai, Toshiro Niki, Akira Tanaka
    MEDICINE 96 (15) e6499  0025-7974 2017/04 [Refereed][Not invited]
    Background: Renal dysplasia is the most important cause of end-stage renal disease in children. The histopathological characteristic of dysplasia is primitive tubules with fibromuscular disorganization. Renal dysplasia often includes metaplastic cartilage. Metaplastic cartilage in renal dysplasia has been explained as occurring secondary to vesicoureteral reflux (VUR). Additionally, renal dysplasia is observed in renal dysplasia-associated syndromes, which are combinations of multiple developmental malformations and include VACTERL association. Case presentation: We observed the following multiple developmental malformations in a 108-day-old male infant during a nephrectomy: a nonfunctioning right kidney with VUR, hemidiaphragmatic eventration, a ventricular septal defect (VSD) with tetralogy of Fallot in the heart, cryptorchidism, and hyperdactylia. These developmental anomalies satisfied the diagnostic criteria for VACTERL association. A surgical specimen of the right nonfunctioning kidney revealed prominent cartilaginous metaplasia in the renal dysplasia with VUR. The densities of the ectopic cartilaginous lesions in this nonfunctioning kidney were extraordinarily high compared with other renal dysplasia cases. Giemsa banding of his genome produced normal results. The patient has not undergone further detailed genomic investigation. Conclusion: This case might be a novel type of VACTERL association, that is, renal dysplasia combined with prominent cartilaginous metaplasia, tetralogy of Fallot and VSD of the heart, hemidiaphragmatic eventration, and hyperdactylia.
  • Hideo Nakai, Taiju Hyuga, Shina Kawai, Taro Kubo, Shigeru Nakamura
    Investigative and Clinical Urology 58 (Suppl 1) S46 - S53 2466-054X 2017 [Refereed][Not invited]
    Vesicoureteral reflux (VUR) is one of the most common diseases in pediatric urology and classified into primary and secondary VUR. Although posterior urethral valve (PUV) is well known as a cause of the secondary VUR, it is controversial that minor urethral deformity recognized in voiding cystourethrography represents mild end of PUV spectrum and contributes to the secondary VUR. We have been studying for these ten years congenital urethral obstructive lesions with special attention to its urethrographic and endoscopic morphology as well as therapeutic response with transurethral incision. Our conclusion to date is that congenital obstructive lesion in the postero-membranous urethra is exclusively PUV (types 1 and 3) and that severity of obstruction depends on broad spectrum of morphological features recognized in PUV. Endoscopic diagnostic criteria for PUV are being consolidated.
  • Shigeru Nakamura, Taiju Hyuga, Shina Kawai, Taro Kubo, Hideo Nakai
    EUROPEAN JOURNAL OF PEDIATRIC SURGERY 26 (4) 368 - 375 0939-7248 2016/08 [Refereed][Not invited]
    Purpose This study aims to evaluate the endoscopic morphological features of congenital posterior urethral obstructions in boys with refractory daytime urinary incontinence and/or nocturnal enuresis. Patients and Methods A total of 54 consecutive patients underwent endoscopy and were diagnosed with a posterior urethral valve (PUV) (types 1-4). PUV type 1 was classified as severe, moderate, or mild. A transurethral incision (TUI) was mainly performed for anterior wall lesions of the PUV. Voiding cystourethrography and pressure flow studies (PFS) were performed before and 3 to 4 months after TUI. Clinical symptoms were evaluated 6 months after TUI, and outcomes were assessed according to PFS waveform pattern groups (synergic pattern [SP] and dyssynergic pattern [DP]). Results All patients had PUV type 1 and/or 3 (i.e., n = 34 type 1, 7 type 3, and 13 types 1 and 3). There were severe (n = 1), moderate (n = 21), and mild (n = 25) cases of PUV type 1. According to PFS, SP and DP were present in 43 and 11 patients, respectively. TUI was effective in the SP group and symptoms improved in 77.4 and 69.3% of patients with daytime incontinence and nocturnal enuresis, respectively. Almost no effect was observed in the DP group. A significant decrease in the detrusor pressure was observed at maximum flow rate using PFS in the SP group. Conclusions PUV type 1 encompassed lesions with a spectrum of obstructions ranging from severe to mild, with mild types whose main obstructive lesion existed at the anterior wall of urethra occurring most frequently in boys with refractory daytime urinary incontinence and/or nocturnal enuresis.
  • Hyuga T, Kawai S, Nakamura S, Kubo T, Nakai H
    The Journal of urology 196 (2) 542 - 547 0022-5347 2016/08 [Refereed][Not invited]
  • Kenji Ishikura, Osamu Uemura, Yuko Hamasaki, Hideo Nakai, Shuichi Ito, Ryoko Harada, Motoshi Hattori, Yasuo Ohashi, Ryojiro Tanaka, Koichi Nakanishi, Tetsuji Kaneko, Kazumoto Iijima, Masataka Honda
    PEDIATRIC NEPHROLOGY 31 (1) 105 - 112 0931-041X 2016/01 [Refereed][Not invited]
    Vesicoureteral reflux (VUR) is associated with an increased risk of kidney disorders. It is unclear whether VUR is associated with progression from chronic kidney disease (CKD) to end-stage kidney disease (ESKD) in children with congenital anomalies of the kidney and urinary tract (CAKUT). We conducted a 3-year follow-up survey of a cohort of 447 children with CKD (stage 3-5). Rates of and risk factors for progression to ESKD were determined using the Kaplan-Meier method and Cox regression respectively. Congenital anomaly of the kidney and urinary tract was the primary etiology in 278 out of 447 children; 118 (42.4 %) had a history of VUR at the start of the cohort study. There were significantly more boys than girls with VUR, whereas the proportions were similar in children without VUR. The types of urinary anomalies/complications of the two groups were significantly different. Three-year renal survival rates of the groups were not significantly different, irrespective of CKD stage. Age < 2 years and age after puberty, stage 4 or 5 CKD, and heavy proteinuria, but not history of VUR, were significantly associated with progression to ESKD. History of VUR at the start of follow-up was not associated with the progression of stage 3-5 CKD in children with CAKUT.
  • Nakamura S, Hyuga T, Kawai S, Nakai H
    The Journal of urology 194 (5) 1402 - 1406 0022-5347 2015/11 [Refereed][Not invited]
  • Akihiro Kanematsu, Shiro Tanaka, Kazuyoshi Johnin, Shina Kawai, Shigeru Nakamura, Masaaki Imamura, Koji Yoshimura, Yoshihide Higuchi, Shingo Yamamoto, Yusaku Okada, Hideo Nakai, Osamu Ogawa
    Journal of Pediatric Urology 9 (1) 57 - 61 1477-5131 2013/02 [Refereed][Not invited]
    Objective: We created software for patterning uroflowmetry (UFM) curves, and validated its utility. Patients and Methods: The software patterns a given UFM curve upon four parameters: sex, voided volume, maximal flow rate, and amplitude of fluctuation. Using the software, 6 urologists from 4 institutes assessed 30 test curves. Further, 329 UFM curves obtained from children presenting to 3 institutes for daytime and/or nighttime wetting were assessed. Clinical presentation was divided into 3 groups: group A, daytime incontinence group B, non-monosymptomatic nocturnal enuresis without daytime wetting and group C, monosymptomatic nocturnal enuresis. Results: Using the software, inter-rater agreement ranged from 0.85 to 1.00 (mean, 0.93 ± 0.04). It could pattern 310 out of 329 clinical curves. In each institute, the tower pattern was prevalent according to severity of daytime symptoms, although not significantly. The merged data showed that the percent tower pattern significantly correlated with presence of daytime symptoms (groups A, B, and C, 29.7%, 27.0%, and 16.3%, respectively p < 0.05). No correlation with daytime symptoms was noted for fluctuated (staccato and interrupted) and plateau patterns. Conclusion: The software creates a common platform for evaluating pediatric UFM, enabling extraction of common and biased features of different cohorts, and their integration into one single cohort. © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
  • Takashi Watanabe, Shigeki Matsubara, Tomoe Ikeda, Shina Kawai, Shigeru Nakamura, Hideo Nakai
    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 39 (1) 415 - 419 1341-8076 2013/01 [Refereed][Not invited]
    A married woman of reproductive age had labial adhesion with voiding difficulty. She and her husband had not been bothered by their inability to engage in sexual intercourse for the 10 years of their marriage. Surgical incision and reconstruction disclosed the normal vaginal vestibule and urethral meatus. Six months after surgery, her labium was fully open without recurrence. We must be aware that labial adhesion may occur and be hidden in a woman of reproductive age, even when the patient does not notice any abnormality in her genitalia.
  • Shigeru Nakamura, Shina Kawai, Taro Kubo, Toshiharu Kihara, Kenichi Mori, Hideo Nakai
    BJU INTERNATIONAL 107 (8) 1304 - 1311 1464-4096 2011/04 [Refereed][Not invited]
    What's known on the subject? and What does the study add? We have clarified that there exist two types of voiding urodynamics (pressure-flow-study) for congenital urethral obstruction in boys; one is synergic pattern (SP) and the other is dyssynergic pattern (DP). In terms of daytime incontinence and nocturnal enuresis, the transurethral endoscopic incision of these obstructive lesions is only effective in the SP type, while never effective in the DP type. The synergic pattern (SP) seems to represent simple anatomical obstruction, while the dyssynergic pattern (DP) may represent anatomical obstruction complicated with functional obstruction. The efficacy of endoscopic incision to mild forms of congenital urethral obstruction has been controversial, especially in terms of nocturnal enuresis. One of the reasons for the controversy is due to the lack of pre-and post-operative urodynamic assessment with its linkage to symptomatic change. We have, for the first time in the world, systematically conducted voiding urodynamic study for those elusive lesions seen in enuretic boys. Conclusively, for simple mechanical obstruction (SP), we confirmed that some voiding urodynamic parameters improve after the endoscopic incision, parallel to symptomatic improvement, while in the rest (DP) endoscopic incision is never effective. The cause of this ineffectiveness seemed to be due to persistent functional obstruction having superimposed on mechanical obstruction. The result of the study urges us to be more keen to diagnose and treat the mild congenial urethral obstruction as well as the concomitant functional obstruction in boys with nocturnal enuresis. OBJECTIVE center dot To evaluate the clinical significance of congenital obstructive lesions of the posterior urethra in boys with refractory primary nocturnal enuresis. PATIENTS AND METHODS center dot VCUG was performed in 43 consecutive boys who visited our department from April 2004 to April 2009 who were unresponsive to conservative treatment. 20 patients of the 43 patients, underwent TUI. VCUG and UDS were performed before and 3-4 months after TUI. center dot In UDS, the maximum flow rate (Q(max)), maximum bladder capacity, and post-voiding residual urine volume were determined using uroflowmetry (UFM), and the detrusor pressure (P(det)) at Q(max) was determined in a pressure flow study (PFS). center dot Clinical outcome was evaluated 3-4 months and 6 months after TUI. RESULTS center dot In VCUG performed 3-4 months after TUI, improvement was observed in urethral morphology in all patients. In preoperative PFS, two patterns were observed: 13 patients (65%) had a synergic pattern (SP) in which the P(det) increased with increasing urinary flow rate simultaneously with the initiation of voiding and seven (35%) had a dyssynergic pattern (DP) in which the P(det) was not coincident with the initiation of voiding, but was higher immediately before voiding than at Q(max). TUI was effective only in the SP group: symptomatic improvement was observed in 87.5% of patients with daytime incontinence and 77% of patients with nocturnal enuresis 6 months after TUI. center dot In the DP group, no effect was observed (0%). With regard to changes in UDS parameters, a significant decrease (P = 0.0004) was observed in the P(det) at Q(max) and a significant increase (P = 0.036) was observed in the maximum bladder capacity in the SP group, whereas no significant differences were noted in any parameters in the DP group. CONCLUSION center dot Two voiding urodynamic patterns with different clinical outcomes of TUI were detected among patients with congenital posterior urethral obstruction, the underlying disease of refractory primary nocturnal enuresis in boys.
  • Tomoyuki Kuwata, Shigeki Matsubara, Shigeru Nakamura, Hideo Nakai
    PEDIATRICS INTERNATIONAL 53 (2) 281 - 282 1328-8067 2011/04 [Refereed][Not invited]
  • Matsuda Y, Yamada M, Arai T, Inoue H, Ichiki A, Okuda Y, Yasuoka A, Nakai H
    Masui. The Japanese journal of anesthesiology 58 (5) 609 - 612 0021-4892 2009/05 [Refereed][Not invited]
  • Satoshi Kitahara, Ryo Sato, Kosaku Yasuda, Gaku Arai, Hideo Nakai, Hiroshi Okada
    INTERNATIONAL JOURNAL OF UROLOGY 15 (7) 621 - 624 0919-8172 2008/07 [Refereed][Not invited]
    Objective: To survey practice patterns in surgical treatment for urethral distraction defect associated with pelvic fracture (PFUDD) and to analyze outcomes of the treatment in Japan. Methods: A questionnaire on surgical treatment for PFUDD to 3307 Japanese consultant urologists was sent. Responses were collected and statistically analyzed. Results: The number of respondents was 1290 (39%). Patients surgically treated for PFUDD in the previous 5 years totaled 0 for 919 urologists (71%), one to two for 283 (22%), and three to ten for 83 (7%) urologists. Realignment for PFUDD was carried out within 2 weeks in 205 patients (23%), after 2-6 months in 607 (69%) patients, and after more than 6 months in 72 (8%) patients. Urologists operated on 361 (61%) patients endoscopically (ES), 108 (18%) by open anastomosis (OA) and 101 (17%) by pull-through operation (PT). According to the operator's impression, success rates were 65% for ES, 79% for PT and 69% for OA. Re-operation (RO) rates were 43%, 25% and 26% for ES, PT, and OA, respectively, (ES vs PT or OA; P < 0.05). Postoperative repeated urethral dilatation (PORUD) was required in 71% of ES, 77% of PT and 38% of OA cases (OA vs ES or PT; P < 0.05). Conclusions: PFUDD represents a rare disorder for Japanese urologists. Deferred endoscopic realignment is the preferred treatment option. Success rates were not different among three surgical treatments. OA was superior to ES and PT in terms of PORUD and RO.
  • Toshiharu Kihara, Hideo Nakai, Ken-ichi Mori, Ryo Sato, Satoshi Kitahara, Kosaku Yasuda
    INTERNATIONAL JOURNAL OF UROLOGY 15 (3) 235 - 240 0919-8172 2008/03 [Refereed][Not invited]
    We described various types of congenital urethral anomalies seen in boys with LUTS such as refractory enuresis. Their urethrograpic and endoscopic finding were reviewed and the effect of trans-urethral incision (TUI) was analyzed. We evaluated 67 boys with lower urinary tract symptoms (LUTS, mean: 9 years old), in a period of three and a half years. A voiding cystourethrogram (VCUG) was performed in 37 patients and if we suspected a urethral abnormality, endoscopy was performed. Congenital urethral obstruction was diagnosed from VCUG and endoscopic findings and classified into Types 1, 3 and 4 posterior urethral valves (PUV) according to Douglas Stephens' description. Trans-urethral incision (TUI) was carried out for congenital urethral obstruction and the effect was judged three months later. On VCUG, 17 patients (45.8%) had an abnormal urethral configuration. On endoscopy, nine patients (24.3%) were diagnosed as having PUV. The effect of TUI on PUV excluding Type 3 was 80%, while that on Type 3 was 25%. The incidence of PUV compared to bulbar urethral narrowing was significantly different from that described in previous Japanese reports, but similar to other countries. The reason is thought to be the lack of standardized interpretations of VCUG images and endoscopic findings, resulting in the overestimation of the bulbar urethral lesion. The incidence of PUV in Japanese boys with LUTS was higher than had ever been described. The improvement rate by TUI was high in PUV excluding Type 3, but low in Type 3. The ring like strictures at the bulbar urethra may be less important than has previously been thought.
  • Tsuneki Suzuki, Kosaku Yasuda, Tomonori Yamanishi, Satoshi Kitahara, Hideo Nakai, Shin Suda, Hiromi Ohkawa
    NEUROUROLOGY AND URODYNAMICS 26 (6) 767 - 772 0733-2467 2007 [Refereed][Not invited]
    Aims: To evaluate the effect of functional continuous magnetic stimulation (FCMS) on urgency incontinence in randomized, sham-controlled manner. Methods: Thirty-nine patients with urgency incontinence, 16 males and 23 females (aged 66.0 +/- 16.5 years), who were refractory to pelvic floor muscle training (PFMT), were randomly assigned either to the treatment schedule performing 10-week active treatment, followed by 4-week non-treatment interval and then by 10-week sham treatment (A-S, n = 20) or to that performing the sham treatment first followed by 10-week active treatment (S-A, n = 19). Results: At 10 weeks, the number of leaks/week, the total score of the International Consultation on Incontinence-Questionnaire: Short Form (ICIQ-SF), and maximum cystometric capacity (MCC) were significantly improved as compared with the initial levels (P < 0.001, P < 0.001, and P = 0.003, respectively) in the former group, but not in the latter group. Four (20.0%) patients were cured in the A-S group, while no patient was cured in the S-A group. At the end of the A-S schedule (24 weeks of study), the effect of the active treatment was still maintained at a significantly improved level, as compared with the initial level. At the end of the S-A schedule, the number of leaks/week was significantly improved as compared with the initial level and with its 10-week level (P < 0.001 and P = 0.049, respectively), as well as ICIQ-SF total score (P = 0.001 and P = 0.006, respectively). MCC significantly increased from its initial level (P = 0.030). Conclusion: Magnetic stimulation was effective on urgency incontinence in comparison to sham stimulation in this small patient group.
  • Junko Miyamoto, Hiroshi Asanuma, Hideo Nakai, Tomonobu Hasegawa, Hajime Nawata, Yukihiro Hasegawa
    Clinical Pediatric Endocrinology 15 (4) 151 - 162 0918-5739 2006 [Refereed][Not invited]
    The prevalence of abnormalities in androgen receptor gene (AR) among patients with ambiguous genitalia is unknown. Moreover, endocrinological data from prepubertal patients with AR mutation are very limited. Thus, the aim of this study was to examine the prevalence of abnormalities in AR among patients with both ambiguous genitalia, which was defined as a combination of two or more genital abnormalities (i.e. hypospadias, microphallus (penile length < 25 mm), hypoplastic scrotum, bifid scrotum, undescended testis) in this study, and normal to elevated T levels. We also compared the endocrinological data of prepubertal patients with AR mutation and ambiguous genitalia with that of those without the AR mutation. We screened 26 Japanese prepubertal 46,XY patients (five from three families were included) with both ambiguous genitalia and normal to elevated T levels. Mutations in AR were found in three (two of the three were related). Among the 23 patients without mutation in AR, the steroid 5-alpha-reductase 2 gene (SRD5A2) was also examined in eight patients with elevated T/dehydrotestosterone ratio after the hCG (> 10) or with undervirilized family members. No mutation in SRD5A2 was found. Characteristics of the three patients with mutation in AR were compared with the 23 patients without mutation. In two patients, basal T levels (0.3, 0.2 ng/ml) and peak T levels after the hCG tests (8.3, 8.5 ng/ml) tended to be higher, and the peak LH/ peak FSH ratios after the GnRH tests (4.6, 4.0) were higher than in patients without mutation, at the ages of 1 yr and 9 mo and 3 yr and 8 mo, respectively. In conclusion, an abnormality in either AR or SRD5A2 was not common among patients with ambiguous genitalia and normal testosterone secretion. Elevated peak LH/peak FSH ratio (≥4) after the GnRH test in addition to detectable basal T levels and elevated peak T levels after the hCG test may infer AR abnormality in prepubertal patients with ambiguous genitalia at the age of one and over, although further study is needed, because our data were limited. Copyright© 2006 by The Japanese Society for Pediatric Endocrinology.
  • Tomonori Yamanishi, Kosaku Yasuda, Satoshi Kitahara, Hideo Nakai, Ken-Ichiro Yoshida, Hiroyuki Iizuka
    NEUROUROLOGY AND URODYNAMICS 25 (7) 815 - 819 0733-2467 2006 [Refereed][Not invited]
    Aims: beta-adrenoceptors are the predominant beta-adrenoceptor subtype present in the bladder and urethra. This study investigates the effects of 138-355, an active-metabolite of TT-138 and beta(3)-adrenoceptor agonist, on relaxation of the human detrusor in vitro. Methods: Tumor-free tissue samples of human bladder muscle from 39 patients undergoing total cystectomy due to bladder cancer were obtained, and the mucosa and serosa were removed. Tissues were mounted in 5 or 10 ml organ baths containing Krebs solution, which was gassed with 95% O-2 and 5% CO2. Resting tension of 1g was obtained. When the contraction had stabilized, increasing concentrations of beta adrenoceptor agonists (non-selective, isoprenaline; beta(2)-selective, clenbuterol; beta(3)-selective, 138-355 and BRL37344) and propiverine (a non-selective anti-muscarinic antagonist) were added cumulatively and concentration-relaxation curves (CRCs) were obtained. CRCs to 138-355 were obtained in the absence and presence of SR59230A, a beta(3)-selective antagonist, and antagonist affinity values (pA(2)) were calculated from the Schild plot. Results: Isoproterenol, clenbuterol, 138-355 and BRL37344 concentration-dependently relaxed isolated human urinary bladder strips with pEC(50) value being 6.76 +/- 0.17, 5.23 +/- 0.22, 5.80 +/- 0.26 and 5.90 +/- 0.28, respectively. Following antagonist assay, it was observed that concentration-relaxation curves to 138-355 was competitively antagonized by beta(3)-adrenoceptor antagonist, SR59230A, with a pA(2) value of 7.01 +/- 0.45 and with a Schild slope of 0.72 +/- 0.07. Conclusions: Involvement of the beta(3)-adrenoceptor appears to be greater than that of the beta(3)-adrenoceptor for relaxations of the human bladder. The relaxation response of 138-355 appears to be mediated via the beta(3)-adrenoceptor stimulation. (c) 2006 Wiley-Liss, Inc.
  • H Takayasu, Y Ishimaru, Y Kisaki, H Nakai, Y Ueda, H Ikeda
    INTERNATIONAL JOURNAL OF UROLOGY 12 (5) 497 - 499 0919-8172 2005/05 [Refereed][Not invited]
    Xanthogranulomatous pyelonephritis (XGP), a morphological and clinical variant of chronic pyelonephritis, is an uncommon disease in children. It is characterized by the destruction of the renal parenchyma and replacement by granulomatous tissue containing foamy lipid-laden macrophages and is classified into diffuse and focal XGP. We present a case of diffuse XGP in a child with myotonic dystrophy complicated by cerebral palsy and discuss the importance of correct diagnosis and preoperative management to reduce inflammation and improve malnutrition associated with the disease.
  • M Fukami, R Horikawa, T Nagai, T Tanaka, Y Naiki, N Sato, T Okuyama, H Nakai, S Soneda, K Tachibana, N Matsuo, S Sato, K Homma, G Nishimura, T Hasegawa, T Ogata
    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 90 (1) 414 - 426 0021-972X 2005/01 [Refereed][Not invited]
    We report on molecular and clinical findings in 10 Japanese patients ( four males and six females) from eight families ( two pairs of siblings and six isolated cases) with Antley-Bixler syndrome accompanied by abnormal genitalia and/or impaired steroidogenesis. Direct sequencing was performed for all the 15 exons of cytochrome P450 oxidoreductase gene (POR), showing two missense mutations (R457H and Y578C), a 24-bp deletion mutation resulting in loss of nine amino acids and creation of one amino acid (L612_W620delinsR), a single bp insertion mutation leading to frameshift (I444fsX449), and a silent mutation (G5G). R457H has previously been shown to be a pathologic mutation, and computerized modeling analyses indicated that the 15A>G for G5G could disturb an exonic splicing enhancer motif, and the remaining three mutations should affect protein conformations. Six patients were compound heterozygotes, and three patients were R457H homozygotes; no mutation was identified on one allele of the remaining one patient. Clinical findings included various degrees of skeletal features, such as brachycephaly, radiohumeral synostosis, and digital joint contractures in patients of both sexes, normal-to-poor masculinization during fetal and pubertal periods in male patients, virilization during fetal life and poor pubertal development without worsening of virilization in female patients, and relatively large height gain and delayed bone age from the pubertal period in patients of both sexes, together with maternal virilization during pregnancy. Blood cholesterol was grossly normal, and endocrine studies revealed defective CYP17A1 and CYP21A2 activities. The results suggest that Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis is caused by POR mutations, and that clinical features are variable and primarily explained by impaired activities of POR-dependent CYP51A1, CYP17A1, CYP21A2, and CYP19A1.
  • Yoshino A, Honda M, Ikeda M, Tsuchida S, Hataya H, Sakazume S, Tanaka Y, Shishido S, Nakai H
    Pediatric nephrology (Berlin, Germany) 19 (11) 1267 - 1272 0931-041X 2004/11 [Refereed][Not invited]
  • H Fujita, A Yoshii, J Maeda, K Kosaki, S Shishido, H Nakai, M Awazu
    PEDIATRIC NEPHROLOGY 19 (5) 554 - 557 0931-041X 2004/05 [Refereed][Not invited]
    We describe a 1-year-old boy with congenital varicella syndrome who had vesicoureteral reflux (VUR) and neurogenic bladder. His mother had varicella during the 3rd month of pregnancy. At birth the patient presented with right microphthalmia, right microcornea, and persistent hyperplastic primary vitreous of the right eye. He had chronic constipation from 3 months of age. He had urinary tract infection at I year of age. Urological investigation revealed left grade V VUR and neurogenic bladder. His varicella zoster virus IgG titer measured by ELISA was 39.4 antibody index (normal <0.1). He had repeated episodes of urinary tract infection despite antibiotic prophylaxis and clean intermittent catheterization, and underwent a uretero-vesiconeostomy at 2 years of age. Maternal infection during early pregnancy and the serological evidence of varicella zoster IgG antibodies without a history of varicella after birth led to the diagnosis of congenital varicella syndrome. Urogenital anomalies have previously been described in 14 cases of congenital varicella syndrome. Most of these patients had neurogenic bladder, the pathophysiology of which could be explained by the known neurotropic nature of the virus.
  • M Yano, S Kitahara, K Yasuda, T Yamanishi, H Nakai, R Yanagisawa, M Morozumi, Y Homma
    INTERNATIONAL JOURNAL OF UROLOGY 11 (5) 288 - 294 0919-8172 2004/05 [Refereed][Not invited]
    Aim: To evaluate the extent to which our newly developed questionnaire, the Saitama Prostate Symptom Score (SPSS), for prostatic symptom scoring reflects objective findings in benign prostatic hyperplasia (clinical BPH) and to compare it with the International Prostate Symptom Score (IPSS) with regard to diagnostic sensitivity in clinical BPH. Methods: In this study, both the SPSS and the IPSS were self-administered by patients. Free uroflowmetry, a pressure-flow study and the measurement of prostatic volume were carried out. Results: There was no significant correlation between the results of the IPSS questionnaire and the urethral obstruction grade estimated by Schaefer or Abrams-Griffiths nomograms. The total score of the SPSS was correlated with these nomograms (P = 0.0487 and P = 0.0413, respectively). There was no significant correlation between the results of the IPSS questionnaire and the total volume or transition zone volume of the prostate, whereas the total score of the SPSS correlated with the total volume of the gland and transition zone volume (P = 0.0044 and P = 0.0051, respectively). Conclusion: This study revealed the SPSS to correlate with objective findings satisfactorily. However, there are still several aspects of the SPSS which need to be improved upon, and the questionnaire should be studied in larger numbers of patients suffering from lower urinary tract symptoms.
  • K Shimada, H Kakizaki, M Kubota, M Taki, H Takeuchi, Y Hiramatsu, S Hosokawa, Y Hosoda, H Nakai, T Yamaguchi
    INTERNATIONAL JOURNAL OF UROLOGY 11 (3) 129 - 132 0919-8172 2004/03 [Refereed][Not invited]
  • H Nakai, T Yamanishi, K Yasuda, S Kitahara, T Suzuki
    NEUROUROLOGY AND URODYNAMICS 23 (7) 618 - 622 0733-2467 2004 [Refereed][Not invited]
    Aim: To examine the potential correlation between urethral function and lower urinary tract Symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Methods: Thirty-one patients with clinical BPH, who were confirmed to have benign prostatic enlargement (BPE) of 20 ml or more, were enrolled into the study. A mark-sheet questionnaire was used for obtaining the LUTS history. Multichannel pressure-flow urodynamic studies were performed and external urethral sphincter pressure (PEUS), intravesical pressure (PVES), and bladder neck pressure (PBN) were recorded both at maximum cystometric capacity and during voiding with 5-microtip transducers, for the purpose of detecting BPE-specific urodynamic findings at different levels within the urethra. Results: There was a positive correlation between hesitancy and detrusor bladder neck dyssynergia (DBND) (P - 0.0011) and between incomplete emptying and low PBN at maximum cystometric capacity (P = 0.0425). The hesitancy proved to have no correlation with bladder neck opening time (TBNO). Conclusion: Urodynamic evaluation of urethral function was beneficial for attributing LUTS to clinical BPH. Among various parameters, DBND was the most specific to clinical BPH, suggesting it to be a situation where a steep rise in PBN or prostatic urethral pressure remains greater than the increasing PVES, resulting in sustained difficulty in opening the bladder neck and subsequently the subjective sensation of hesitancy. (C) 2004 Wiley-Liss, Inc.
  • Nakai H, Asanuma H, Shishido S, Kitahara S, Yasuda K
    Pediatrics international : official journal of the Japan Pediatric Society 45 (5) 634 - 641 1328-8067 2003/10 [Refereed][Not invited]
  • S Shishido, H Asanuma, H Nakai, Y Mori, H Satoh, Kamimaki, I, H Hataya, M Ikeda, M Honda, A Hasegawa
    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 14 (4) 1046 - 1052 1046-6673 2003/04 [Refereed][Not invited]
    Chronic allograft nephropathy (CAN) is due to both immunologic and non-immunologic factors and results in the development of nonspecific pathologic features that may even be present in long-term well-functioning renal allografts. To investigate the natural history of CAN and potential risk factors associated with progression of these histologic lesions, this study evaluated the of histologic alterations of 124 sequential protocol biopsies performed at 2, 3, and 5 yr after transplantation in 46 patients who exhibited histologic evidence of CAN in the 1-yr biopsy. The occurrence of late acute rejection (AR) greater than 4 mo posttransplant was significantly associated with the development of histologic CAN. In contrast, early clinical AR occurring within 3 mo had no impact on the subsequent development of CAN at I yr. Subclinical AR was evident in association with CAN in 50%, 32%, 19%, and 16% of cases with CAN at 1, 2, 3, and 5 yr, respectively. These acute lesions correlated significantly with histologic progression defined as an increased CADI score of the follow-up biopsies. Furthermore, a group of patients who exhibited repeated subclinical AR in the sequential follow-up biopsies had a lower creatinine clearance at 5 yr after transplantation and worse long-term graft survival. In contrast, the absence of evidence of acute inflammation in association with CAN at any time point was associated with minimal deterioration in renal function or progression of renal lesions during the observation period. These results suggest that the persistence of chronic active inflammation may be responsible for the histologic progression of CAN.
  • H Nakai, H Kakizaki, R Konda, Y Hayashi, S Hosokawa, S Kawaguchi, H Matsuoka, K Nonomura, K Shimada, T Kawamura
    JOURNAL OF UROLOGY 169 (1) 309 - 312 0022-5347 2003/01 [Refereed][Not invited]
    Purpose: We evaluate clinical characteristics of primary vesicoureteral reflux in infants in a multicenter study in Japan with special reference to the relation of renal parenchymal damage to urinary tract infection and gender. Materials and Methods: Infants younger than 1 year old with primary vesicoureteral reflux were recruited from 14 hospitals during the 3-year registration period beginning in January 1996 and ending in December 1998. Various clinical parameters as well as renal parenchymal lesion on dimercaptosuccinic acid scintigraphy were evaluated. Results: Of 356 infants enrolled 296 (83%) were male and 60 (17%) were female. In 85% of infants presenting symptom was febrile urinary tract infection. There were 204 bilateral (57%) and 152 unilateral (43%) cases. Reflux was bilateral in 56% of males versus 65% of females, and high grade (grades IV and V) in 58% of males versus 55% of females. Diffuse parenchymal lesion was similarly noted in infants with or without prior urinary tract infection (38% and 46%, respectively) and was more often noted in male than in female infants (42% versus 25%). Conclusions: Despite the current use of screening prenatal ultrasound, many infants are still diagnosed as having vesicoureteral reflux only after the occurrence of urinary tract infection. The greater severity of renal parenchymal lesion in male infants combined with similar incidence of diffuse parenchymal lesion in those with or without prior infection suggests preexisting congenital abnormalities in the male refluxing kidney.
  • Konda R, Kakizaki H, Nakai H, Hayashi Y, Hosokawa S, Kawaguchi S, Matuoka H, Nonomura K, Reflux Nephrology Forum, Japanese Prospective, Study Group
    Nephron 92 (4) 812 - 816 1660-8151 2002/12 [Refereed][Not invited]
  • Higuchi A, Kawamura T, Nakai H, Hasegawa Y
    Pediatrics international : official journal of the Japan Pediatric Society 44 (5) 540 - 542 1328-8067 2002/10 [Refereed][Not invited]
  • Ikeda M, Yata N, Kamei K, Mori K, Ishikura K, Hataya H, Honda M, Asanuma H, Shishido S, Nakai H
    Pediatric nephrology (Berlin, Germany) 17 (1) 71  0931-041X 2002/01 [Refereed][Not invited]


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