Biomedical subjects

Yoshihiko Hirao

Publications and source records attributed to Yoshihiko Hirao.

At least 19 recordsLinked to original sources

PubMed2006

Expression of hyperpolarization-activated cyclic nucleotide-gated cation channels in rat dorsal root ganglion neurons innervating urinary bladder.

Afferent pathways innervating the urinary bladder consist of myelinated Adelta- and unmyelinated C-fibers, the neuronal cell bodies of which correspond to medium and small-sized cell populations of dorsal root ganglion (DRG) neurons, respectively. Since hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel currents have been identified in various peripheral sensory neurons, we examined the expression of isoforms of HCN channels in the L6-S1 spinal cord and bladder afferent neurons from L6-S1 DRG in rats. Among HCN-1, HCN-2 and HCN-4 channel subtypes, positive staining with HCN-2 antibodies was found in the superficial dorsal horn of the spinal cord and small- and medium-sized unidentified DRG neurons. In dye-labeled bladder afferent neurons, HCN-2-positive cells were found in approximately 60% of neurons, and HCN-2 was expressed in both small- and medium-sized neurons with a higher ratio (expression ratio: 61% and 50% of neurons, respectively) compared with unidentified DRG neurons, in which the HCN expression ratio was 47% and 21% of small- and medium-sized cells, respectively. These results suggest that HCN-2 is the predominant subtype of HCN channels, which can control neuronal excitability, in small-sized C-fiber and medium-sized Adelta fiber DRG neurons including bladder afferent neurons, and might modulate activity of bladder afferent pathways controlling the micturition reflex.

Animals↗

PubMed2006

Decrease in nocturnal urinary levels of arginine vasopressin in patients with nocturnal polyuria.

OBJECTIVES: To elucidate whether heart function and endocrine levels of arginine vasopressin (AVP) or solute diuresis is associated with the nocturnal voided volume, and whether the urinary AVP could be a parameter for screening for nocturnal polyuria caused by AVP insufficiency. METHODS: A total of 50 patients were enrolled in this study. The blood and urine samples were obtained every 6 hours at 6 pm, 12 am, 6 am, and 12 pm. Atrial natriuretic peptide and brain natriuretic peptide were measured at admission. All voided urine samples were collected every 6 hours for examination. The evaluation items were AVP, osmolarity, sodium, potassium, chloride, and creatinine in blood and urine. RESULTS: The patients were classified into a group with nocturnal polyuria (n = 21) and a group without nocturnal polyuria (n = 25). There was no significant difference in atrial natriuretic peptide, brain natriuretic peptide, electrolytes in blood and urine, and plasma AVP of each sample between the two groups, but urinary AVP/urinary creatinine and urine osmolarity at 12 am and 6 am in the group with nocturnal polyuria were significantly lower than those in the group without nocturnal polyuria. The nocturnal voided volume correlated with urinary AVP/urinary creatinine level in the urine samples obtained at 12 am and 6 am. CONCLUSIONS: The present data have demonstrated that the significant decrease in urinary AVP/urinary creatinine level at 6 am may contribute to the increased nocturnal voided volume followed by nocturia and that the circadian rhythm disorder of AVP can be predicted by a noninvasive test measuring urinary AVP/urinary creatinine in the urine voided early in the morning.

Aged↗

PubMed2006

Quality of care associated with number of cases seen and self-reports of clinical competence for Japanese physicians-in-training in internal medicine.

BACKGROUND: The extent of clinical exposure needed to ensure quality care has not been well determined during internal medicine training. We aimed to determine the association between clinical exposure (number of cases seen), self- reports of clinical competence, and type of institution (predictor variables) and quality of care (outcome variable) as measured by clinical vignettes. METHODS: Cross-sectional study using univariate and multivariate linear analyses in 11 teaching hospitals in Japan. Participants were physicians-in-training in internal medicine departments. Main outcome measure was standardized t-scores (quality of care) derived from responses to five clinical vignettes. RESULTS: Of the 375 eligible participants, 263 (70.1%) completed the vignettes. Most were in their first (57.8%) and second year (28.5%) of training; on average, the participants were 1.8 years (range = 1-8) after graduation. Two thirds of the participants (68.8%) worked in university-affiliated teaching hospitals. The median number of cases seen was 210 (range = 10-11400). Greater exposure to cases (p = 0.0005), higher self-reports of clinical competence (p = 0.0095), and type of institution (p < 0.0001) were significantly associated with higher quality of care, using a multivariate linear model and adjusting for the remaining factors. Quality of care rapidly increased for the first 100 to 200 cases seen and tapered thereafter. CONCLUSION: The amount of clinical exposure and levels of self-reports of clinical competence, not years after graduation, were positively associated with quality of care, adjusting for the remaining factors. The learning curve tapered after about 200 cases.

Clinical Competence↗

PubMed2006

A phase I trial of vaccination of CA9-derived peptides for HLA-A24-positive patients with cytokine-refractory metastatic renal cell carcinoma.

PURPOSE: A phase I peptide vaccination trial was done in patients with progressive cytokine-refractory metastatic renal cell carcinoma (RCC) to assess both the toxicity and capability to induce immune responses of three peptides (CA9p219-227, p288-296, and p323-331) derived from CA9, a tumor-associated antigen ubiquitously expressed in RCC. EXPERIMENTAL DESIGN: Twenty-three patients positive for human leukocyte antigen (HLA)-A24 with histologically confirmed RCC were enrolled. Eligibility included progressive disease after standard cytokine therapy with interleukin-2 and/or IFN-alpha. Patients were vaccinated s.c. with the three peptides emulsified in incomplete Freund's adjuvant at 2-week intervals. Pre- and post-vaccination blood samples were obtained for toxicity assessment and immunologic studies. Patients were monitored for clinical responses on a 3-monthly basis. RESULTS: Vaccinations were well tolerated without any major adverse event. Most of the patients developed peptide-specific CTLs and/or immunoglobulin G reactive to the peptides after the 6th or 9th vaccination, followed by a gradual increase in both CTL frequency and levels of peptide-reactive serum IgG. Three patients with multiple lung metastases showed partial responses with disappearance and shrinking of metastatic lesions. Additionally, stable disease for >6 months was observed in six patients (median duration, 12.2 months). Moreover, the median survival time of all patients who were progressive at trial enrollment after failing immunotherapy was 21.0 months (5-35 months). CONCLUSIONS: These results suggest that vaccination of these peptides is safe and recommended for further trials for HLA-A24-positive metastatic RCC patients.

Adult↗

PubMed2006

The case for androgen deprivation as primary therapy for early stage disease: results from J-CaP and CaPSURE.

PURPOSE: We analyzed the outcome of primary androgen depletion therapy, which has gained more attention as a potential therapeutic option in patients with localized or locally advanced prostate cancer as it has been increasingly implemented despite limited data on its therapeutic impact in Japan and the United States. MATERIALS AND METHODS: We analyzed data from CaPSURE and the Japanese Prostate Cancer study. RESULTS: In Japan primary androgen depletion therapy has long been the treatment of choice for localized and locally advanced prostate cancer. Based on CaPSURE data the frequency of primary androgen depletion therapy being chosen to treat localized and locally advanced disease is also increasing in clinical practice in the United States. A study of the outcomes of endocrine therapy is currently being performed in Japan by the Japanese Prostate Cancer Study Group. CONCLUSIONS: It is important to obtain such information about the role of primary androgen depletion therapy for localized and locally advanced prostate cancer from studies of natural history and clinical trials. It is also important to update practical treatment guidelines.

Androgen Antagonists↗

PubMed2006

The endoscopic surgical skill qualification system in urological laparoscopy: a novel system in Japan.

PURPOSE: The Japanese Urological Association, and Japanese Society of Endourology and ESWL have established the Endoscopic Surgical Skill Qualification System in urological laparoscopy. The system consists of a urological section as well as gynecology and general surgery sections. We present details of the Endoscopic Surgical Skill Qualification System and year 1 results. MATERIALS AND METHODS: Endoscopic Surgical Skill Qualification System requirements test the ability to complete common laparoscopic surgeries in each field. In urology applicants are required to complete adrenalectomies or nephrectomies appropriately and safely. Applicants should have 2 years of experience with laparoscopic practice, in addition to having completed a 6-year formal urological training program. Also, each surgeon must have performed more than 20 laparoscopic surgeries. According to assessment guidelines applicant skills are assessed by 2 referees who view unedited videotapes showing the entire laparoscopic procedure. To establish these referees 6 expert referees were first selected and 23 were then chosen from 36 referee applicants. Each referee had completed more than 100 laparoscopic surgeries and was chosen after video assessments by the 6 initial expert referees. RESULTS: Of 5,600 certified urologists in Japan 205 applied to this system in its first year, including 6 expert referees and 36 referee applicants. After video assessments by the referees 136 applicants were certified as having appropriate skills, resulting in a 66% pass rate. CONCLUSIONS: The Endoscopic Surgical Skill Qualification System has just started but it has drawn a lot of attention from the public. We hope that this qualification system will help prevent complications of urological laparoscopic surgeries and promote safer surgical procedures.

Clinical Competence↗

PubMed2006

Sustained prophylactic effect of intravesical bacille Calmette-Guérin for superficial bladder cancer: a smoothed hazard analysis in a randomized prospective study.

OBJECTIVES: A previous meta-analysis had revealed that intravesical chemotherapy was effective in reducing the recurrence of superficial bladder cancer only in the early phase, the phase thought to be caused by tumor cell implantation and/or residual tumor cells. To ascertain the sustained prophylactic effect of intravesical bacille Calmette-Guérin (BCG) after transurethral resection of bladder tumor (TURBT), we compared the estimation of the duration of the effect with that of doxorubicin. METHODS: Eighty eligible patients with superficial bladder cancer (Stage Ta or T1, grade 1 or 2) were included. Patients were randomly allocated into two groups: the BCG group (six weekly instillations of 80 mg BCG [Tokyo 172 strain]) and the doxorubicin group (17 instillations of 20 mg doxorubicin). A comparison between the smoothed hazards of tumor recurrence was performed using a kernel function method. RESULTS: All 80 patients (40 each in the BCG and doxorubicin groups) were compared. The median follow-up period was 667 days (range 64 to 1607). The risk of recurrence was significantly lower in the BCG group than in the doxorubicin group (P = 0.017, log-rank test). A smoothed hazard curve depicting the reduced risk of recurrence in the BCG group suggested that BCG is not only efficacious in the early phase of recurrence (up to 500 days after TURBT), but also in the late phase, and the latter is thought to include second primary tumors (new tumors). CONCLUSIONS: BCG instillation may prevent tumor recurrence caused by both tumor cell implantation and second primary tumors.

Adjuvants, Immunologic↗

PubMed2006

Prostate-specific antigen changes as a result of chlormadinone acetate administration to patients with benign prostatic hyperplasia: a retrospective multi-institutional study.

BACKGROUND: Antiandrogens used to treat benign prostatic hyperplasia (BPH) may affect the diagnosis of prostate cancer by decreasing serum prostate-specific antigen (PSA) values. We conducted a retrospective survey of BPH patients treated with chlormadinone acetate (CMA) and analysed the effect of CMA on their PSA values. METHODS: A chart-based, retrospective, multi-institutional survey of clinically diagnosed patients with BPH who had been treated with CMA (Prostal; 50 mg/day) was conducted. The patients were divided into three groups according to their baseline PSA values: <4 ng/mL, Group I; >or=4 ng/mL and <10 ng/mL, Group II; and >or=10 ng/mL, Group III. The changes in the PSA values from baseline after 16, 26, and 52 weeks of CMA therapy were predicted using a nonlinear regression model analysis. RESULTS: Data from 192 of the 303 enrolled patients were analysed. The predicted percent changes from baseline among all patients after 16, 26, and 52 weeks of treatment were -49.6%, -49.8%, and -49.9%, respectively. The corresponding values were -42.4%, -43.7% and -43.8% in Group I; -57.4%, -58.4% and -58.5% in Group II; and -50.6%, -50.6% and -50.6% in Group III, respectively. CONCLUSION: The PSA values reached a nadir, approximately -50% of the baseline, after 16 weeks of CMA administration and remained at the same level thereafter. When CMA is used to treat BPH patients, the possibility of abnormal increases in PSA associated with prostate cancer must be considered; if prostate cancer is suspected, prompt testing, including a biopsy, should be performed.

Aged↗

PubMed2006

Sexuality and seeking medical help for erectile dysfunction in young adults with spina bifida.

OBJECTIVES: The objectives of this study were to evaluate the correlation between the sexual function of spina bifida (SB) patients and Sharrard classification, touch sensation on the penis, to examine if SB patients who are sexually active have erectile dysfunction (ED) on the International Index of Erectile Function-5 (IIEF5), and to clarify if they seek medical treatment for ED. METHODS: Thirty-six male SB patients aged over 18 years were enrolled. A questionnaire was sent to all patients that included the following items: touch sensation on the penis, psychogenic erection, rigidity at erection, ejaculation, orgasm and experience in sexual intercourse. In addition, patients who had experience in sexual intercourse were asked about ED through the use of the IIEF5 and whether or not they sought medical help for their ED. RESULTS: Twenty-six patients responded. The positive rates of psychogenic erection, rigidity at erection, ejaculation and orgasm were 85%, 54%, 88% and 65% respectively. Psychogenic erection and ejaculation correlated with Sharrard classification. Rigidity at erection and orgasm correlated with touch sensation on the penis. Eleven patients had experience in sexual intercourse and six of them were diagnosed as having ED on the IIEF5. There were no factors correlating with ED. None of the patients sought medical advice and none was treated for ED. CONCLUSIONS: Sexual function of SB patients could be predicted by Sharrard classification and touch sensation on the penis to some degree. However, ED did not correlate with sexual function. Therefore, we should not evaluate the neurological loss but instead provide adequate information.

Adolescent↗

PubMed2006

Efficacy of primary hormone therapy for localized or locally advanced prostate cancer: results of a 10-year follow-up.

OBJECTIVE: To evaluate the efficacy of primary hormone therapy for localized or locally advanced prostate cancer, by analysing the 10-year survival rates for men with localized or locally advanced prostate cancer treated with primary hormone therapy or prostatectomy. PATIENTS AND METHODS: Between February 1993 and March 1995, men with T1b, T1c or T2-3 N0M0 prostate cancer were enrolled. In all, 176 men who had a prostatectomy were assigned to Study 1 and were given adjuvant luteinizing hormone-releasing hormone (LHRH) agonist; 151 men who did not have a prostatectomy were assigned to Study 2 and had LHRH agonist monotherapy or combined androgen blockade. They were followed until death, loss to follow-up, or until the end of the observation period (31 March 2004). We analysed all cases in each study as a single population, and compared Study 1 with Study 2. RESULTS: The mean patient ages were 67.2 years in Study 1 and 75.7 years in Study 2. During a median of 10.4 years of follow-up, 20 men in Study 1 and 17 in Study 2 died from prostate cancer, and 21 men in Study 1 and 50 in Study 2 died from other causes. In Study 1, the 10-year overall survival rate was 73% and the 10-year cause-specific survival rate was 86%, vs 41% and 78% in Study 2. Overall survival curves were similar to expected survival curves in both studies. There was no significant difference between studies in cause-specific survival. CONCLUSIONS: The progression of prostate cancer was retarded by primary hormone therapy in men with localized or locally advanced prostate cancer. With primary hormone therapy or prostatectomy, the men had a life-expectancy similar to that of the normal population.

Aged↗

PubMed2006

Polyamines as an inhibitor on erythropoiesis of hemodialysis patients by in vitro bioassay using the fetal mouse liver assay.

The pathogenesis of anemia in patients with chronic renal failure has been greatly attributed to erythropoietin (EPO) deficiency. Recently, however, there has been some thought that uremic inhibitors might suppress the activity of EPO and reduce the maturation of erythropoiesis. Polyamines are well known to be involved in the regulation of cellular proliferation and differentiation. Furthermore, the polyamine levels in the serum or erythrocytes are elevated in chronic hemodialysis patients, and can be lowered immediately by hemodialysis. In the present study, we first measured the polyamines levels (putrescine, spermidine, spermine) by high performance liquid chromatography (HPLC) in 20 chronic hemodialysis patients, and investigated the effects of polyamines on erythropoiesis by in vitro bioassay using fetal mouse liver cells. The direct effects of polyamines in erythroid colony formation in the medium with and without EPO were evaluated. Each polyamine level in chronic hemodialysis patients was higher than in the healthy subjects, and a significant negative correlation was found between polyamines and erythropoiesis. Polyamines inhibited the activity of EPO, but they did not have any direct effect on colony formation of the fetal mouse liver cells. These results suggest that polyamines have inhibitory effects on the proliferation or maturation of erythroid precursor cells and are intimately involved in the pathogenesis of renal anemia in chronic hemodialysis patients.

Adolescent↗

PubMed2006

[Case of proximal-type epithelioid sarcoma of the perineum].

A 31-year-old man was referred to our department for investigation and treatment of a rapidly-growing mass in the perineal region. MRI showed a periurethral tumor in the perineal region measuring 3.5cm in maximum diameter and bilateral inguinal lymph nodes enlargement. Therefore, the tumor was extirpated immediately with bilateral inguinal lymphadenectomy. The pathological examination with immunohistochemistry revealed that the tumor was proximal-type epithelioid sarcoma. Multidisciplinary therapy with irradiation, chemotherapy, and tumor ablation with a microwave tissue coagulator, was not effective for local recurrence and metastasis, and finally he died of progressive disease 14 months after the operation. Epithelioid sarcoma originating from the thigh or trunk is classified into the proximal-type, which shows significantly poorer prognosis than the distal-type that develops in the distal extremities. The proximal-type epithelioid sarcoma of the perineum is rare and, to our knowledge, the present report is the fourth case in the Japanese literatures.

Adult↗

PubMed2006

[Operative position suitable for transvaginal excision of urethral diverticulum or closure of urethrovaginal fistula].

Among the various surgeries in female urology, transvaginal excision of urethral diverticulum needs careful and meticulous procedures in order to avoid some operative complications, such as urethral stricture or urethrovaginal fistula. In the present report, we present a woman with urethral diverticulum who initially underwent transvaginal excision of diverticulum in the dorsal lithotomy position, but she was complicated with urethrovaginal fistula postoperatively. Unfortunately, we failed to repair her fistula when she underwent excision of the fistula in the dorsal lithotomy position. With reconsideration of an operative position useful for transvaginal surgery, we succeeded in fistula closure in the Jackknife prone reverse-lithotomy position, and thereafter, two subsequent patients with urethral diverticulum were successfully treated with transvaginal excision of diverticulum in this operative position. In the transvaginal approach to the peri-urethral disorders, the Jackknife prone reverse-lithotomy position was notably superior to the dorsal lithotomy position with the following advantages: (1) the surgeons can easily operate in a bright and large surgical site without any blind view. (2) the surgeons can dissect and suture safely and accurately. (3) the assistants also can help in the operation bimanually in the same view as the surgeon when the posterior vaginal wall is fixed with a retractor.

Adult↗

PubMed2006

[Initial conservative treatment for grade 3 Ta-1 superficial bladder cancer].

We retrospectively investigated the therapeutic outcomes of our series of 7 Ta and 62 T1 bladder cancers with grade 3 (G3) malignancy in 61 men and 8 women having a mean age of 66.2 years. Following transurethral resection of bladder tumor (TURBT), 35 and 6 patients received intravesical instillations of bacillus Calmette-Guerin (BCG) and anthracycline-derivants, respectively, whereas 15 received no adjuvant therapy. Five and 2 patients received systemic and local chemotherapy with irradiation, respectively, and six underwent radical cystectomy for invasive potential. The 5-year nonrecurrence, progression-free, and overall (cancer-specific) survival rates were 66, 82%, and 76 (88%), respectively, after a median follow-up of 52 months. The 5-year non-recurrence rates were 24% in non-adjuvant, 85% in BCG, 0% in anthracycline-derivants, 65% in systemic and local chemoradiation therapy, and 68% in cystectomy. The 5-year progression-free and overall (cancer-specific) survival rates of the patients treated with BCG instillation were 91% and 94 (100)%. There were no significant differences in the 5-year non-recurrence and progression-free rates between 12 patients with carcinoma in situ (CIS) and 23 patients without CIS. Complete TUR of all visible tumors and a reliable histopathological diagnosis of appropriate specimens bearing the muscle layer are mandatory for assessment of recurrence. G3 Ta-1 bladder cancers and CIS showed a high risk of recurrence, and required aggressive treatment. Since BCG therapy following TURBT significantly reduced the risk of recurrence and progression, adjuvant BCG therapy is considered to be the most promising initial conservative treatment for G3 Ta-1 bladder cancers.

Adjuvants, Immunologic↗

PubMed2005

Association of HER-2 polymorphism with Japanese sporadic prostate cancer susceptibility.

BACKGROUND: Genetic polymorphisms may affect the development of prostate cancer (Pca). HER-2 is a proto-oncogene that has an important role in many human cancers, including Pca. To determine the association of the HER-2 gene with Japanese sporadic Pca, we analyzed the frequency of codon 655 (A/G, isoleucine, or valine) in case and control group. METHODS: We genotyped Ile 655 Val in Pca patients (n = 285) and in matched controls (n = 233). Statistical analyses were performed by Fisher's exact test and logistic regression analysis. RESULTS: We observed a significantly lower frequency of the Val655 allele in the Pca patients (14.7%) compared to the control group (26.2%) (P = 0.0025, odds ratio (OR) = 0.476, 95% CI = 0.306-0.740). This SNP was not found to be correlated with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. CONCLUSIONS: Our results indicate that the frequency of Val655 in HER-2 was significantly lower in Japanese Pca patients, however, it was recently reported that Val655 was significant higher in breast cancer patients. This contradictory observation in prostate and breast cancer patients is interesting considering the opposite hormonal sensitivity of these two cancers.

Aged↗

PubMed2005

The current status of perioperative chemotherapy for invasive bladder cancer: a multiinstitutional retrospective study in Japan.

BACKGROUND: We conducted a multiinstitutional analysis to clarify the clinical significance of perioperative chemotherapy, in invasive bladder cancers in Japan, and to identify the patient subpopulations who could benefit from perioperative chemotherapy. METHODS: A total of 913 consecutive patients aged less than 80 years who underwent radical cystectomy for invasive bladder cancer from 1990 to 2000 at 32 Japanese hospitals were retrospectively analyzed. Median follow-up was 3.8 years (range, 0.1 to 11.8 years). RESULTS: In total, 341 patients (37.3%) were treated with perioperative chemotherapy, including neoadjuvant chemotherapy (n = 174), adjuvant chemotherapy (n = 114), or a combination of both chemotherapies (n = 53). With cisplatin-based combination chemotherapy, the MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen was the one most frequently used for perioperative chemotherapy, but the average number of cycles was distinctly less than that in reported randomized trials. MEC (methotrexate, epirubicin, and cisplatin) chemotherapy had efficacy similar to that of the MVAC regimen. On analysis of patients stratified by stage, the overall survival of patients with adjuvant chemotherapy was significantly better than that of those without adjuvant chemotherapy, in patients with pT2b, pN0 or pT3, pN0 (P = 0.016 or 0.020, respectively), but adjuvant chemotherapy had no, or the opposite, effect on patients with pT2a, pN0, pT4, pN0, or pTany, pN+. On the other hand, neoadjuvant chemotherapy provided a statistically significant survival benefit only for patients with clinical T3N0 (P = 0.015). Of note, in the high-risk subgroup, the overall survival rate for patients with complete response (CR) after neoadjuvant chemotherapy was significantly better than that of patients with partial response (PR) or no change (NC)/progressive disease (PD) (P = 0.043). CONCLUSION: In Japan, cisplatin-based combination chemotherapy has been the main modality adopted perioperatively for high-risk patients with radical cystectomy. This study's clinical results indicated that perioperative chemotherapy may improve survival in patients with T3N0 or pT2b/pT3, pN0 bladder cancer.

Adult↗

PubMed2005

Nocturia in men with lower urinary tract symptoms is associated with both nocturnal polyuria and detrusor overactivity with positive response to ice water test.

OBJECTIVES: To investigate whether detrusor overactivity (DO) and the response to the ice water test (IWT) influence nighttime urinary frequency in patients with lower urinary tract symptoms. METHODS: A total of 114 patients with lower urinary tract symptoms, who were older than 50 years, with an International Prostate Symptom Score 8 or more points and a quality of life index of 2 or greater, were evaluated by a 48-hour frequency-volume chart, free flowmetry, pressure flow study, and IWT. RESULTS: The DO-positive IWT responders had a significantly greater bladder outlet obstruction index than did the DO-positive IWT nonresponders and the DO-negative IWT nonresponders. The DO-positive IWT responders had significantly more frequent nocturia and smaller nighttime maximal and minimal voided volumes than did the DO-negative IWT nonresponders without any difference in the nocturnal voided volume. The patients with nocturia two or more times had a significantly larger nocturnal voided volume and smaller nighttime minimal voided volume than the patients with nocturia less than two times. The incidence of DO-positive IWT responders was significantly greater among the patients with nocturia three or more times than that among those with nocturia less than three times. In the multivariate logistic model, the nocturnal voided volume and nighttime minimal voided volume were independently associated with nocturia two or more times and the DO-positive IWT responders were independently associated with nocturia three or more times. CONCLUSIONS: Once high-grade bladder outlet obstruction induces C-fiber-related DO, it is strongly suggested that this process, together with nocturnal polyuria, plays an important role in the consequent clinical manifestations of nocturia in patients with lower urinary tract symptoms.

Administration, Intravesical↗

PubMed2005

Loss of blood group A antigen expression in bladder cancer caused by allelic loss and/or methylation of the ABO gene.

Loss of ABO blood group antigen expression has been reported in transitional cell carcinoma (TCC) of the bladder. Synthesis of the ABO blood group antigen was genetically determined by allelic variants of the ABO gene assigned on 9q34.1. We analyzed loss of heterozygosity (LOH) and promoter hypermethylation of the ABO gene in TCC and compared them with alterations of A antigen expression in TCC, dysplasia and normal urothelium. A total of 81 samples of TCC of the bladder obtained from transurethral resection (TUR) (n=44) and radical cystectomy (n=37) were examined. Expression of the A antigen was evaluated by immunohistochemical staining (IHC) using anti-A antigen monoclonal antibody. LOH of the ABO gene locus was examined by blunt-end single-strand DNA conformational polymorphism (SSCP) analysis using flouresence-based auto sequencer. Promoter hypermethylation of the ABO gene were examined by bisulfite PCR-SSCP (BiPS) analysis and/or methylation-specific PCR (MSP). Loss of A allele and/or hypermethylation were significantly associated with abnormal expression of the A antigen in cases undergoing TUR (P=0.02) and radical cystectomy (P=0.0005). For the analysis of the concomitant dysplasia in 23 cases with TCC of the bladder, the expression of the A antigen was maintained, regardless of the A allelic loss or methylation status in the tumor. In conclusion, A allelic loss and hypermethylation in the promoter region of the ABO gene showed significant correlation with reduction of A antigen expression in TCC, while the expression of the A antigen is maintained in concomitant dysplasia or normal urothelium, suggesting that loss of the ABO gene and/or its promoter hypermethylation is a specific marker for TCC.

ABO Blood-Group System↗