High Prevalence of Dysplastic Development of Sacral Vertebral Arches in Pediatric Enuresis.

PURPOSE: This is the first report to compare 3-dimensional computed tomography (3D-CT) images between pediatric patients with enuresis and children without lower urinary tract symptoms who underwent pelvic CT for other reasons. METHODS: Forty-seven children (33 boys and 14 girls) with primary enuresis underwent 3D-CT of sacrococcygeal bones. The control group consisted of 138 children (78 boys and 60 girls) who underwent pelvic CT for other reasons. First, we determined the presence or absence of unfused sacral arches at the L4-S3 levels in both cohorts. Subsequently, we compared the fusion of sacral arches in age- and sex-matched children from these 2 groups. RESULTS: Dysplastic sacral arches, characterized by lack of fusion at 1 or more levels of the S1-3 arches, were observed in nearly all patients in the enuresis group. In the control group (n=138), 54 of 79 children over 10 years old (68%) exhibited fused sacral arches at 3 S1-3 levels. All 11 control children under 4 years old displayed at least 2 unfused sacral arches at the S1-3 levels. In a comparative study of age- and sex-matched patients with enuresis and control children aged 5 to 13 years (n=32 for each group, with 21 boys and 11 girls; mean age, 8.0±2.2 years [range, 5-13 years]), only 1 patient (3%) in the enuresis group exhibited fusion of all S1-3 arches. In contrast, 20 of 32 control group participants (63%) had 3 fused sacral arches (P<0.0001). CONCLUSION: Sacral vertebral arches typically fuse by the age of 10 years. However, in this study, children with enuresis exhibited a significantly elevated prevalence of unfused sacral arches, suggesting that dysplastic development of sacral vertebral arches may play a pathological role in enuresis.

Thermal denaturation and autoxidation profiles of carangid fish myoglobins.

Although myoglobin (Mb) has been considered to be one of the well-characterized proteins, screening of post-genomic era databases revealed the lack of adequate information on teleost Mbs. The present study was aimed to investigate stability and functional features of Mbs from three teleosts of the same family. To unfold how primary structure influences the stability and function of proteins, Mbs were purified from the dark muscles of three carangids, namely, yellowtail, greater amberjack, and silver trevally. Thermostabilities measured by circular dichroism (CD) spectrometry revealed species-specific thermal denaturation pattern, i.e., silver trevally > yellowtail > greater amberjack Mbs. On the other hand, autoxidation rate constants of the ferrous forms of those three carangid Mbs showed positive correlation between the ferrous state of the heme iron and rising temperature. The order of autoxidation rate was in the order of greater amberjack > yellowtail > silver trevally Mbs. The finding of the present study denotes that the thermal stability is not necessarily correlated with the functional stability of carangid Mbs even though their primary structures shared high homology (84-94%).

Structural and dynamical characteristics of tropomyosin epitopes as the major allergens in shrimp.

Ingestion of marine invertebrates often causes food allergy, where the major allergens have been reported to be derived from tropomyosin (TM). Intact or the digestive fragments of food allergens generally show resistance to digestion, which is usually attributable to the structural stability (or rigidity). The difference in the structural and dynamical characteristics between the epitope and the non-epitope regions in TM has not yet been well understood. In the present study, molecular dynamics simulation was performed at constant pHs for shrimp TM. By analyzing the main-chain dihedral angle fluctuations and local α-helix contents, we found that the epitope regions are more stable than the non-epitope counterparts, providing a possible physical reason for the resistance to digestion in the epitopes regions. The difference of the structural stability between the epitope and the non-epitope regions was largest at low pHs, even though pH dependence of the structural stability in itself was not significant in both regions. The lower content of the Ala cluster in the epitope region is considered to cause the higher stability of the epitope region.

Clinical Guideline for Female Lower Urinary Tract Symptoms.

The "Japanese Clinical Guideline for Female Lower Urinary Tract Symptoms," published in Japan in November 2013, contains two algorithms (a primary and a specialized treatment algorithm) that are novel worldwide as they cover female lower urinary tract symptoms other than urinary incontinence. For primary treatment, necessary types of evaluation include querying the patient regarding symptoms and medical history, examining physical findings, and performing urinalysis. The types of evaluations that should be performed for select cases include evaluation with symptom/quality of life (QOL) questionnaires, urination records, residual urine measurement, urine cytology, urine culture, serum creatinine measurement, and ultrasonography. If the main symptoms are voiding/post-voiding, specialized treatment should be considered because multiple conditions may be involved. When storage difficulties are the main symptoms, the patient should be assessed using the primary algorithm. When conditions such as overactive bladder or stress incontinence are diagnosed and treatment is administered, but sufficient improvement is not achieved, the specialized algorithm should be considered. In case of specialized treatment, physiological re-evaluation, urinary tract/pelvic imaging evaluation, and urodynamic testing are conducted for conditions such as refractory overactive bladder and stress incontinence. There are two causes of voiding/post-voiding symptoms: lower urinary tract obstruction and detrusor underactivity. Lower urinary tract obstruction caused by pelvic organ prolapse may be improved by surgery.

Thermodynamic characterization of muscle tropomyosins from marine invertebrates.

Structural properties of invertebrate muscle tropomyosin (TM) have not been characterized in detail to date. TMs were thus purified from the mantle muscle of Japanese common squid Todarodes pacificus, the foot muscle of tokobushi abalone Haliotis diversicolor and the tail muscle of kuruma prawn Marsupenaeus japonicus, and investigated for their thermodynamic properties by circular dichroism (CD) spectrometry and differential scanning calorimetry (DSC). From the CD spectrometry data, the apparent melting temperature and the apparent free energy of unfolding at 20°C were calculated to be 43.5°C and 14.5 kJ/mol for the squid TM, 43.0°C and 23.9 kJ/mol for the abalone TM, and 47.3°C and 50.2 kJ/mol for the prawn TM, respectively. From the DSC data, the total free energy of unfolding at 20°C was calculated to be 129 kJ/mol, 253 kJ/mol, and 271 kJ/mol for the squid, abalone, and prawn TMs, respectively. These results suggest that the thermal stability was in the order of prawn TM>abalone TM>squid TM.

Thermal denaturation profiles of tuna myoglobin.

Myoglobin (Mb) purified from fast skeletal muscle of bluefin tuna Thunnus thynnus orientalis was subjected to thermal treatment, and the denaturation profiles were examined by thermodynamic analysis. Based on the ellipticity or helical content obtained by circular dichroism (CD) spectrometry, it was found that denaturation of tuna Mb consisted of three steps, and that slight structural changes of Mb started below 20 degrees C. However, major structural changes were observed at around 58 and 72 degrees C. Differential scanning calorimetry (DSC) analysis revealed a similar but somewhat different thermal denaturation profile of Mb. In comparison with the denaturing profiles of whale Mb under the same conditions, the thermal stability of tuna Mb was found to be much lower. In the modeled tertiary structures of these Mbs, they were roughly similar to each other, though minor conformational differences were recognized and the total energy was found to be lower for tuna Mb.

Characterization of two tropomyosin isoforms from the fast skeletal muscle of bluefin tuna Thunnus thynnusorientalis.

Fast skeletal muscle tropomyosin (TM) of tunas is composed of nearly equimolar amount of two isoforms designated alpha-TM and beta-TM expediently based on their migration behavior in SDS-PAGE, whereas corresponding TMs from the other fish species are homogenous (alpha-type). The presence of beta-TM is thus specific to tunas so far. The amino acid sequence of beta-TM from bluefin tuna Thunnus thynnus orientalis, which has not been revealed to date unlike alpha-TM, was successfully obtained in this study by cDNA cloning. The coding region of beta-TM cDNA comprised of an open reading frame of 855bp encoding 284 amino acid residues, like most of the TMs. Unexpectedly, the sequence of beta-TM showed high similarity to those of other vertebrate alpha-type TMs including tuna alpha-TM. Phylogenetic analysis also showed that beta-TM has the closest relationship with alpha-TM of tuna. This fact was quite unlike the relation of mammalian alpha- and beta-TMs. Based on the distribution of amino acid substitutions, it was suggested that tuna TM isoforms are the products of different genes. By thermodynamic analysis of native and reconstituted TMs, it was demonstrated that beta-TM is less thermostable than alpha-TM. Proteolytic digestion also supported the lower stability of the former.

The future of urodynamics: non-invasive ultrasound videourodynamics.

A totally non-invasive transperineal urodynamic technique using Doppler ultrasonography has been developed. Normal urine doesn't have blood cells so urine was thought not to produce Doppler effects. However, basic studies confirmed that the decrease of pressure at high velocity (Bernoulli effects) caused dissolved gas to form microbubbles, which are detected by Doppler ultrasonography. Subjects sat and a probe was advanced via remote control to achieve gentle contact with the perineal skin. The digital uroflow data signals and the color Doppler ultrasound video images were processed on a personal computer. This method was viable to diagnose the degree of bladder outlet obstruction. The advantage of being rapid, effective, and equipped with no special attachments allows it to surpass any other non-invasive urodynamic methods. The difference between the echocardiogram and the ultrasound urodynamic system is only the frequency of obtaining velocity information: more than 50 times per minute vs once every several hours, respectively. Although the ultrasound urodynamic system is more difficult to develop than the echocardiogram, one principle is shared by both methods. The patient can void freely without interruptions, there is no contact between the penis and the equipment and it is specifically directed toward non-invasive diagnosis. The development of non-invasive Doppler ultrasound videourodynamics will dramatically expand understanding of voiding function.

Thermostability of striated and smooth adductor muscle tropomyosins from Yesso scallop Mizuhopecten yessoensis.

The striated and smooth adductor muscle tropomyosins (TMs) of Yesso scallop Mizuhopecten yessoensis have been known to express different isoforms, but have not been characterized in detail to date. In the present study, TMs from both muscles of Yesso scallop were purified and their stabilities were compared by circular dichroism (CD) spectrometry and differential scanning calorimetry (DSC). From the CD data, the apparent melting temperature and the apparent free energy of folding at 20 degrees C were calculated to be 30.5 degrees C and -13.4 kJ/mol, and 36.0 degrees C and -31.9 kJ/mol for the striated and smooth muscle TMs, respectively. From the DSC data, DeltaH values were calculated to be 1.87 x 10(3) and 2.19 x 10(3) kJ/mol for striated and smooth muscle TMs. These results suggest that smooth muscle TM has higher thermostability than striated muscle TM. The amino acid residues responsible for such stability difference were considered to be the six amino acid substitutions in the middle region of the TM molecules.

Use of Doppler ultrasound for non-invasive urodynamic diagnosis.

OBJECTIVES: A totally non-invasive transperineal urodynamic technique using Doppler ultrasonography has been developed. METHODS: Since normal urine does not have blood cells, urine was thought not to produce the Doppler effects. However, basic studies confirmed that the decrease of pressure at high velocity (Bernouilli effect) caused dissolved gas to form microbubbles, which are detected by Doppler ultrasonography. Subjects sat and the probe was advanced via remote control to achieve gentle contact with the perineal skin. The digital uroflow data signals and the color Doppler ultrasound video images were processed on a personal computer. The flow-velocity curves from two sites; the distal prostatic urethra just above the external sphincter (V1) and the sphincteric urethra (V2) were plotted against time. The parameters of both the pressure-flow studies and the Doppler ultrasound urodynamic studies were compared in men who had various degrees of obstruction. RESULTS: Functional cross-sectional area at prostatic urethra (A1), calculated by Q(max)/V1, was lower in the group of bladder outlet obstruction (BOO) vs. control group. Velocity ratio (VR), which was calculated by V1/V2, was the parameter having the best correlation with BOO index, though A1 had a similar correlation. This method is viable to diagnose the degree of BOO. CONCLUSIONS: The development of non-invasive Doppler ultrasound videourodynamics (Doppler UDS) will dramatically expand the information on voiding function.

Neural tube defects: prevalence, etiology and prevention.

Spina bifida and anencephaly, the common form of neural tube defects, affect approximately 300 000 newborns each year worldwide. The effectiveness of folic acid supplementation in preventing their occurrence or recurrence has been unambiguous since 1991. In general, the prevalence of these abnormalities has decreased in the past 20 to 30 years because of periconceptional folate supplementation, food fortification in several countries, avoiding exposure to environmental factors, and increased accuracy of prenatal screening for fetal anomalies. Women who are planning to conceive should be informed about the importance of folic acid in fetal development and advised to take 400 microg/day of folic acid supplements. Food fortification with folic acid will ultimately be necessary to reduce the number of patients. Primary prevention of neural tube defects by the periconceptional intake of folic acid is a major public health opportunity and has wide implications in reducing the mortality and morbidity of offspring.

[Periconceptional intake of folate reduces the risk of neural tube defects: awareness among urologists in 2007].

AIMS: Folic acid is one of water-soluble Vitamin B group and plays an important role in proliferating cells of the fetus. A multicentered, randomized control trial proved in 1991 that folic acid supplements of 4 mg per day periconceptionally administered to 1031 women who were recruited from 7 countries and had afflicted prior pregnancy successfully prevented 72% of recurrence of neural tube defects. As a primary prevention method, the Government has recommended to take 400 microgram of folate supplements per day from 4 weeks before and 12 weeks after conception. Because of huge amount of folate being demanded in the first trimester, this vitamin is called as "vitamin for women" or "vitamin for fetuses". We herewith report results of questionnaire study performed among urologists. MATERIALS AND METHODS: A questionnaire was sent July 2007 to 400 urologists randomly selected from the Membership Directory of the Japanese Urological Association 2006 whether they are aware of the role of folic acid and how they guide young women or pregnant women on their life style. One hundred sixty-one responses were obtained (40%). RESULTS: Thirty-six percent of urologists were aware of the important role of folic acid in the critical stage of fetal development, which was significantly elevated compared to 26% observed in 2002 (p = 0.037). Fifty-seven percent of urologists acquired this information through Japanese Urological Association or medical journals, 17% through mass media, and 7% through internet. Those who guided young women or pregnant women to refrain from smoking, to abstain from alcohol, to take well-balanced meals and to take folate supplements were 73%, 62%, 67% and 7%, respectively. Ninety-two percent of urologists agreed to provide this information to young women or pregnant women. CONCLUSION: Birth incidence of spina bifida has been increasing in Japan. In order to suppress incidence of this congenital anomaly, Urologists are requested to send young women a message that maternal periconceptional intake of folate will suppress the risk of congenital anomalies.

[Continuous bladder irrigation following transurethral resection of the prostate (TURP)].

PURPOSE: We investigated whether continuous bladder irrigation after Transurethral Resection of the Prostate (TURP) would prevent catheter obstruction by the clot. MATERIALS AND METHODS: We analyzed data from 761 patients registered in "a multi-institutional study of TURP clinical pathway" sponsored by the Ministry of Health, Labor and Welfare between 2001 and 2003. The difference of clinical backgrounds of the cases, resected weight, operating time, risk of being feverish, risk of catheter obstruction and chance of postoperative Transurethral Fulguration (TUF) between each institution were investigated. The risk factor of catheter obstruction is characterized and the significance of continuous bladder irrigation is discussed. RESULTS: The incidence of catheter obstruction in the four institutions, in which 90% or more of patients underwent continuous bladder irrigation, was significantly lower than that in the three institutions, in which continuous bladder irrigation was performed in selected patients whose hematuria was severe (4.4% VS 12.9%, p<0.001). There was no difference in the frequency of either pyrexia or postoperative TUF. Logistic regression analysis showed that significant factors for catheter obstruction are continuous bladder irrigation, resected tissue weight and preoperative urinary infection. CONCLUSIONS: Routine continuous bladder irrigation achieved a lower incidence of catheter obstruction. However, we recommend that urologists should decide whether to perform routine continuous irrigation, considering the frequency of catheter obstruction, safety, labor and cost.

[Evolution of common clinical path for transurethral resection of prostate (TURP)].

OBJECTIVES: Improvement of perioperative management for transurethral resection of the prostate (TURP) by revising the common clinical path was investigated in multiple hospitals. METHODS: We discussed perioperative outcomes using the common path in 2002 and revised it for 2003. Changes in perioperative outcomes between 2002 and 2003 and differences among hospitals were compared. RESULTS: There were no statistically significant differences in age, proportion of patients with mildly impaired activity of daily living and/or impaired cognition, general anesthesia, operating duration, resected weight, incidence of intraoperative complications and blood transfusion between 2002 and 2003. Although there were no differences in preoperative hospital stay, re-hospitalization rate and charges for surgery and anesthesia, Foley catheter was removed significantly earlier from postoperative day 2.9 to 2.3 and total medical charge significantly decreased from 43,703 to 39,661 units (1 unit = 10 yen). The incidence of postoperative pyrexia increased from 2.4% to 11.2% in 2003, however, the incidences of epididymitis, postoperative bleeding and postoperative difficulty on micturition remained stable. The average and standard deviation of postoperative hospital stay and total medical charge at each hospital decreased, however, differences among hospitals found in 2002 remained in 2003. CONCLUSION: We found that standardization can be accomplished by discussing perioperative management using a common path in multiple hospitals and revising the path as needed. Common clinical path should be a valid method of advancing standardization in Japan.

Folic acid prevents neural tube defects: international comparison of awareness among obstetricians/gynecologists and urologists.

AIM: It has been suggested that periconceptional intake of folic acid prevents risks of having fetuses afflicted with neural tube defects. We aim to internationally investigate knowledge of the role of folic acid and attitudes toward the life-style of young women of child-bearing age among obstetricians/gynecologists and urologists. METHODS: A questionnaire was sent to obstetricians/gynecologists and urologists residing in Japan, South Korea, Taiwan, North America, Europe, Australia and New Zealand by post or e-mail. The investigation was conducted between December 2002 and November 2004. RESULTS: A mean of 91% of obstetricians/gynecologists and 56% of urologists are aware of the role of folic acid, where Asian urologists knew less compared to those of North America, Europe, Australia and New Zealand. A majority of doctors always, or occasionally, recommend folic acid supplements or multivitamins, well-balanced meals, and the cessation of smoking and drinking. An average of 85% of doctors believes information on folic acid should be disseminated to young women. CONCLUSIONS: A majority of obstetricians/gynecologists and urologists know the importance of periconceptional folic acid in reducing the risk of neural tube defects and have been advising young women to improve their lifestyle.

[Questionnaire survey of peri-operative management of transurethral prostate resection in Japan].

OBJECTIVES: We investigated perioperative management for transurethral resection of the prostate (TURP) in Japan. METHODS: The questionnaire survey was conducted in 1,213 educational institutions for urology. RESULTS: The questionnaires were returned from 722 (60%) institutions. Admission to hospital was most frequently scheduled on preoperative day 1; termination of continuous drip infusion, starting meal intake and walking on postoperative day 1; intravenous antibiotics for three days; removal of Foley catheter on postoperative day 4; oral antibiotics for 7 days; and discharge from hospital on postoperative day 7. CONCLUSION: Although hospitalization was 14 days or less at most institutions, several procedures, especially the administration of prophylactic antibiotics, were fairly varied. Discussions from various perspectives might be needed to standardize the perioperative management of TURP in Japan.

Efficacy, safety and hospital costs of tension-free vaginal tape and pubovaginal sling in the surgical treatment of stress incontinence.

AIM: The efficacy, safety and hospital costs of the tension-free vaginal tape procedure were compared with the pubovaginal sling operation. METHODS: A total of 60 women urodynamically diagnosed as having stress or mixed urinary incontinence were operated on using either the tension-free vaginal tape or pubovaginal sling operation in a prospective manner. Preoperative characteristics of the women were not significantly different for the groups. The women were followed for up to 24 months. RESULTS: In the tension-free vaginal tape group, the operation time was shorter, numbers of analgesics postoperatively required were less and hospital charges were less expensive compared to those in the pubovaginal sling operation (P < 0.01). Kaplan-Meier survival analysis showed a marginal significant difference (P = 0.059) in the objective cumulative cure rates at 24 months between the groups receiving the former (70.3%) and latter (48.3%) procedures. Subjective cure rates were not significantly different (P = 0.101). In both groups, an improvement in quality of life was significant and surgical complications were identical. De novo urge incontinence developed in 6% and 10% in the former and latter, respectively. CONCLUSIONS: The tension-free tape was significantly superior to the pubovaginal sling in terms of operation time, postoperative pain, and hospital charges, but not in cure rates. A longer follow up with a larger sample size is necessary to draw definite conclusions.

Tension-free vaginal tape surgery for stress urinary incontinencne: a prospective multicentered study in Japan.

AIM: To report the prospective multicentered study of the tension-free vaginal tape (TVT) procedure for stress urinary incontinence. METHODS: One hundred and fifty-one women with stress urinary incontinence were operated on by the TVT procedure and were followed up at 3, 12, and 24 months after surgery. Patients' age and body mass index (BMI) averaged 57 years and 23.9, respectively. Forty-nine women were classified as type I, 46 women type II and 56 women type III (McGuire's classification). Local anesthesia was used in the operations on 137 women (91%) and epidural or general anesthesia was used in 14 (9%). Surgical outcomes were analyzed with Kaplan-Meier survival curves. RESULTS: The subjective and objective cumulative cure rates 24 months later were 92% and 77%, respectively (P > 0.05). The TVT operation for women with type III (62%) resulted in a significantly lower cure rate compared to those with type I or with type II (83%) (P < 0.001). Post-operatively a urethral catheter was indwelt one day in 77 women (51%), two days in 14 (9%) and 3-7 days in 60 (40%). Surgical complications were encountered in 43 women (28%). The most frequent was bladder perforation in 24 women followed by postoperative difficulty in urination and de novo urgency. CONCLUSIONS: The TVT surgery was promising for the treatment of stress incontinence because of minimal surgical invasiveness and satisfactory surgical results. Women with type III incontinence resulted in fewer satisfactory outcomes than those with type I or II incontinence.

[Long-term usefulness and safety of the contemporary balloon catheter].

OBJECTIVE: To evaluate usefulness and safety of an indwelling contemporary balloon catheter, we compared complication rates among five methods of urinary tract management. PATIENTS AND METHODS: History of febrile episode, bladder stones, pyuria and the miscellaneous urinary tract problems of 114 patients were retrospectively reviewed. The rates of complications were compared among five types of urinary tract management as clean intermittent catheterization dry (not incontinent) (CIC-dry: n = 33), clean intermittent catheterization with incontinence (CIC-wet: n = 16), clean intermittent catheterization with a contemporary balloon catheter indwelling at night (Contemporary catheter: n = 20), a suprapubic cystostomy catheter indwelling (Cystostomy: n = 22) and permanent urethral balloon catheter indwelling (Urethral catheter: n = 24). The contemporary balloon catheter used consisted of a reusable balloon catheter and a reservoir to inflate the balloon. The patients in the Contemporary catheter group self-inserted the catheter every night before sleeping, and then removed it in the next morning. After use, the catheter was washed with tap water, and stored in a special purpose case filled with disinfectant. RESULTS: The mean follow up period was 41 months. The incidence of febrile episode in CIC-wet was 3.36 times/100 months, Urethral catheter was 2.96, Cystostomy was 1.26, Contemporary catheter was 0.57, and CIC-dry was 0.42. The incidence of febrile episode in CIC-wet and Urethral catheter were significantly higher than in CIC-dry (p<0.05). The incidence of bladder stone in Urethral catheter was 1.11 times/100 months, Cystostomy was 1.05, Contemporary catheter was 0.96, CIC-wet was 0.61, and CIC-dry was 0.21. The Urethral catheter group had significantly higher incidence of bladder stone than CIC-dry (p<0.05). CONCLUSIONS: The indwelling contemporary balloon catheter is recommended for long-term use in CIC-wet group.