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Biomedical subjects

Hideo Nakai

Publications and source records attributed to Hideo Nakai.

14 recordsLinked to original sources

Effects of 138-355, a beta3-adrenoceptor selective agonist, on relaxation of the human detrusor muscle in vitro.

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% CO(2). Resting tension of 1 g 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.

Adrenergic beta-3 Receptor Agonists↗

Diffuse xanthogranulomatous pyelonephritis in a patient with myotonic dystrophy and cerebral palsy.

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.

Adolescent↗

Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients.

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.

Abnormalities, Multiple↗

Genitourinary anomaly in congenital varicella syndrome: case report and review.

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 1 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.

Abnormalities, Multiple↗

Correlation between lower urinary tract symptoms and urethral function in benign prostatic hyperplasia.

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.

Aged↗

Merit of the cuff-shaving procedure in children with chronic infection.

Catheter replacement and cuff-shaving are per-formed as a surgical treatment against tunnel infection(TI) in patients on chronic peritoneal dialysis. The efficacy of catheter replacement is well established, but that of cuff-shaving is not. For the purpose of evaluating the efficacy of cuff-shaving, we compared the time interval between each procedure and subsequent TI. In order to perform this comparison, we reviewed data from 32 cuff-shaving procedures and 29 catheter replacement procedures at Tokyo Metropolitan Kiyose Children's Hospital in the period from 1 March 1991 to 1 May 2001, retrospectively. There was no significant difference in the time interval between each procedure and subsequent TI(P=0.284). The incidence of recurrence was no more than 12.5% for the cuff-shaving procedures. The incidence of peritonitis due to post-surgery TI with the cuff-shaving procedures was 9.3% and 6.8% with the replacement procedure (P=0.725). There was no significant variation in time interval to post-cuff-shaving TI according to the reason for the cuff-shaving procedure. In conclusion,cuff-shaving may be worth considering for TI in adequately selected patients.

Adolescent↗

A pilot study evaluating a new questionnaire for prostatic symptom scoring, the SPSS, and its sensitivity as constructed to objective measures of outflow obstruction.

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.

Aged↗

Clinical characteristics of primary vesicoureteral reflux in infants: multicenter retrospective study in Japan.

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.

Female↗

Changing concepts in urological management of the congenital anomalies of kidney and urinary tract, CAKUT.

Recent advancement in ultrasonographic evaluation has prompted early detection and diagnosis of congenital anomalies in the kidney and urinary tract (CAKUT) in the asymptomatic phase. Consequently, early surgical intervention has become possible in the asymptomatic phase for the purpose of controlling manifestations early, thereby avoiding renal functional deterioration. However, some lesions detected by ultrasonography have been shown to often resolve or disappear without intervention. Thus, it has become more important to identify and understand the natural history of CAKUT. For the precise evaluation of the results of surgical intervention, one must understand the maturational process of renal function during infancy. Without considering this process, we cannot differentiate the renal significance of the surgical management from the natural course of CAKUT. Recent advancement in the field of radioisotopic studies has also made a major contribution to the more precise assessment of renal function. Recent progress in the understanding of the pathophysiology and the natural history of CAKUT has helped rationalize its treatment and management. Improvement in the surgical techniques and tools, together with improvements in pediatric anesthesiology, have made an appreciably positive impact on the outcome. Herein, we present the emerging concepts in the urological management of CAKUT, specifically, multicystic dysplastic kidney, vesicoureteral reflux, congenital hydronephrosis, ectopic ureters and ureteroceles.

Child↗

The impact of repeated subclinical acute rejection on the progression of chronic allograft nephropathy.

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 1 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.

Acute Disease↗

Urinary concentrations of alpha-1-microglobulin and albumin in patients with reflux nephropathy before and after puberty.

We determined urinary concentrations of alpha(1)-microglobulin and albumin in 155 patients with reflux nephropathy including 72 prepubertal (48 males and 24 females) and 83 postpubertal patients (43 males and 40 females) to elucidate the effect of age and gender in the progression of renal damage. Vesicoureteral reflux was resolved in all patients at least two years before enrollment into this study. Renal scarring was diagnosed with (99m)technetium dimercaptosuccinic acid renal scan. More severe renal scarring was found predominantly in male compared to female patients. Urinary alpha(1)-microglobulin levels were significantly lower in postpubertal female patients (mean +/- SD: 1.59 +/- 1.02 mg/g creatinine) than in prepubertal males and females (3.32 +/- 3.53 and 4.06 +/- 4, respectively; p < 0.007 and p < 0.002, respectively), and in postpubertal males (3.69 +/- 2.6; p < 0.002) regardless of severity of renal scarring. In the patients with severe unilateral renal scarring, urinary albumin levels were significantly higher in postpubertal males (81.9 +/- 239.5) than in prepubertal males and postpubertal females (25.8 +/- 63.1 and 13.8 +/- 7.7, respectively; p < 0.05 and p < 0.05, respectively). Our results suggest that glomerular injury may develop during adolescence predominantly in male patients with severe renal scarring. In contrast, renal damage indicated by urinary alpha(1)-microglobulon level appears to be ameliorated in female postpubertal patients. This gender difference may be attributed to sex hormones.

Adolescent↗