Pediatric neurogenic bowel dysfunction: ICCS review document.

INTRODUCTION: The International Children's Continence Society (ICCS) aims to improve the quality of life in children with lower urinary tract dysfunction. A substantial portion of children also have problems with bowel dysfunction. There is a lack of evidence-based information on managing neurogenic bowel dysfunction (NBD) in children. OBJECTIVE/METHODS: The ICCS aimed to provide an up-to-date, selective, non-systematic review of NBD's definitions, assessment, and treatment. RESULTS: Specific definitions and terminology are defined within the document. Recommendations and considerations for physical assessment, history taking, and diagnostic studies are made. Management updates, both surgical and non-surgical, are provided as well as recommendations for follow-up and monitoring of individuals with NBD. CONCLUSION: This review of the current literature will help guide NBD management and research to improve NBD care.

Randomized open-label trial comparing topical prescription triamcinolone to over-the-counter hydrocortisone for the treatment of phimosis.

BACKGROUND: Phimosis is a common condition affecting most infant boys and generally resolves over time without symptoms. Severe cases of phimosis can lead to balanoposthitis, urinary tract infections, and urinary retention. Medical treatment for symptomatic phimosis includes topical corticosteroids with manual foreskin retraction. OBJECTIVE: Over-the-counter hydrocortisone 1% cream was compared in a randomized controlled fashion with prescription triamcinolone 0.1% cream for the medical management of symptomatic phimosis. METHODS: The study institution conducted a randomized open-label trial for the treatment of grades 4-5 phimosis (phimosis grade scale 0-5). Boys aged 3-13 years were randomized to hydrocortisone 1% cream or triamcinolone 0.1% cream dosed at least twice daily for a course of 12 weeks. Instructions were provided for appropriate application and manual retraction of the foreskin. Evaluations were performed at 4, 8, and 12 weeks. Successful completion of the study was determined by reaching phimosis grade 2 or less or after completing 12 weeks of treatment. RESULTS: A total of 52 boys enrolled in the trial, with a total of 32 boys completing the 12-week duration. Of the 13 boys in the hydrocortisone arm, there was a 30.8% success rate at 4 weeks, 53.8% success rate at 8 weeks, and 61.5% success rate at 12 weeks. Of the 19 boys in the triamcinolone arm, there was a 31.6% success rate at 4 weeks, 52.6% success rate at 8 weeks, and 68.4% success rate at 12 weeks. There was no statistical difference between the two arms at each interval. DISCUSSION: To the study authors' knowledge, this is the first open-label trial with direct comparison of hydrocortisone 1% cream with triamcinolone 0.1% cream. The study results support those reported in other studies when each topical steroid was compared with placebo. Limitations of the study include loss to follow-up, unblinded treatment allocation, and reduced power to detect differences by treatment frequency and duration. CONCLUSION: Over-the-counter hydrocortisone 1% cream is not inferior to triamcinolone 0.1% cream when paired with manual retraction for the treatment of grade 4-5 phimosis. Successful treatment response may be seen up to 12 weeks.

Assessment of pediatric bowel and bladder dysfunction: a critical appraisal of the literature.

OBJECTIVE: Bowel and bladder dysfunction (BBD) is a clinical syndrome defined by the coexistence of constipation and lower urinary tract symptoms. Although BBD is a common condition in pediatric urology and can cause significant stress to patients/parents, clinical diagnosis of BBD has not been standardized. Bowel and bladder dysfunction instruments have gained popularity over the past decade to aid in diagnosis. In this review, the currently published BBD symptom questionnaires were summarized and an analysis on their psychometric validation process was provided. SUBJECTS/PATIENTS: PubMed was searched for articles on BBD symptom questionnaires/instruments/surveys since 2000. Two investigators (R.Y.J. & M.S.K.) conducted the search in duplicate. The search was limited to English language. The included search terms were 'dysfunctional elimination syndrome', 'bowel and bladder dysfunction', 'dysfunctional voiding', 'voiding dysfunction symptom score', and 'dysfunctional voiding symptom scale'. Reference lists of included studies were screened for missed studies. Unpublished abstracts presented at the following scientific meetings were also manually searched for: the American Urological Association, the Society for Pediatric Urology, and the American Academy of Pediatrics Section on Urology. Exclusion criteria included articles in languages other than English, articles not related to BBD questionnaires, and articles not pertaining to pediatric patients. RESULTS: After initial search, a total of 54 articles were obtained. Of the seven questionnaires reviewed, only one did not measure sensitivity or specificity. Almost all questionnaires showed excellent discriminative property with an Area under the curve (AUC) >0.85. Criterion validity was not reported in any of the questionnaires. Known-group validation was used as a common method to evaluate construct validity. Internal consistency was reported in 2 studies, and only 1 study measured questionnaire responsiveness during initial validation. CONCLUSIONS: Although BBD is a common pediatric urology condition; a large amount of heterogeneity exists in the questionnaires' psychometric testing and validation process. To further improve the diagnosis and management of BBD in pediatric patients, there is a need for consensus on the gold standard questionnaire measure.

Sterilization of Lung Matrices by Supercritical Carbon Dioxide.

Lung engineering is a potential alternative to transplantation for patients with end-stage pulmonary failure. Two challenges critical to the successful development of an engineered lung developed from a decellularized scaffold include (i) the suppression of resident infectious bioburden in the lung matrix, and (ii) the ability to sterilize decellularized tissues while preserving the essential biological and mechanical features intact. To date, the majority of lungs are sterilized using high concentrations of peracetic acid (PAA) resulting in extracellular matrix (ECM) depletion. These mechanically altered tissues have little to no storage potential. In this study, we report a sterilizing technique using supercritical carbon dioxide (ScCO2) that can achieve a sterility assurance level 10(-6) in decellularized lung matrix. The effects of ScCO2 treatment on the histological, mechanical, and biochemical properties of the sterile decellularized lung were evaluated and compared with those of freshly decellularized lung matrix and with PAA-treated acellular lung. Exposure of the decellularized tissue to ScCO2 did not significantly alter tissue architecture, ECM content or organization (glycosaminoglycans, elastin, collagen, and laminin), observations of cell engraftment, or mechanical integrity of the tissue. Furthermore, these attributes of lung matrix did not change after 6 months in sterile buffer following sterilization with ScCO2, indicating that ScCO2 produces a matrix that is stable during storage. The current study's results indicate that ScCO2 can be used to sterilize acellular lung tissue while simultaneously preserving key biological components required for the function of the scaffold for regenerative medicine purposes.

Imaging submandibular pathology in the paediatric patient.

A wide range of pathologies may arise from the submandibular space (SMS) or submandibular gland (SMG) in children. We review herein the normal anatomy of the SMS and describe the role of imaging in the evaluation of SMS lesions. A schematic approach for the categorisation of SMS pathology based on imaging characteristics is provided.

The effect of exposure to wood smoke on outcomes of childhood pneumonia in Botswana.

SETTING: Tertiary hospital in Gaborone, Botswana. OBJECTIVE: To examine whether exposure to wood smoke worsens outcomes of childhood pneumonia. DESIGN: Prospective cohort study of children aged 1-23 months meeting clinical criteria for pneumonia. Household use of wood as a cooking fuel was assessed during a face-to-face questionnaire with care givers. We estimated crude and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for treatment failure at 48 h by household use of wood as a cooking fuel. We assessed for effect modification by age (1-5 vs. 6-23 months) and malnutrition (none vs. moderate vs. severe). RESULTS: The median age of the 284 enrolled children was 5.9 months; 17% had moderate or severe malnutrition. Ninety-nine (35%) children failed treatment at 48 h and 17 (6%) died. In multivariable analyses, household use of wood as a cooking fuel increased the risk of treatment failure at 48 h (RR 1.44, 95%CI 1.09-1.92, P = 0.01). This association differed by child nutritional status (P = 0.02), with a detrimental effect observed only among children with no or moderate malnutrition. CONCLUSIONS: Exposure to wood smoke worsens outcomes for childhood pneumonia. Efforts to prevent exposure to smoke from unprocessed fuels may improve pneumonia outcomes among children.

Conserving large populations of lions - the argument for fences has holes.

Packer et al. reported that fenced lion populations attain densities closer to carrying capacity than unfenced populations. However, fenced populations are often maintained above carrying capacity, and most are small. Many more lions are conserved per dollar invested in unfenced ecosystems, which avoid the ecological and economic costs of fencing.

Aberrations in the arcuate fasciculus are associated with auditory verbal hallucinations in psychotic and in non-psychotic individuals.

The pathophysiology of auditory verbal hallucinations (AVH) is still unclear. Cognitive as well as electrophysiological studies indicate that a defect in sensory feedback (corollary discharge) may contribute to the experience of AVH. This could result from disruption of the arcuate fasciculus, the major tract connecting frontal and temporo-parietal language areas. Previous diffusion tensor imaging studies indeed demonstrated abnormalities of this tract in schizophrenia patients with AVH. It is, however, difficult to disentangle specific associations with AVH in this patient group as many other factors, such as other positive and negative symptoms, medication or halted education could likewise have affected tract integrity. We therefore investigated AVH in relative isolation and studied a group of non-psychotic individuals with AVH as well as patients with AVH and non-hallucinating matched controls. We compared tract integrity of the arcuate fasiculus and of three other control tracts, between 35 non-psychotic individuals with AVH, 35 schizophrenia patients with AVH, and 36 controls using diffusion tensor imaging and magnetization transfer imaging. Both groups with AVH showed an increase in magnetization transfer ratio (MTR) in the arcuate fasciculus, but not in the other control tracts. In addition, a general decrease in fractional anisotropy (FA) for almost all bundles was observed in the patient group, but not in the non-psychotic individuals with AVH. As increased MTR in the arcuate fasciculus was present in both hallucinating groups, a specific association with AVH seems plausible. Decreases in FA, on the other hand, seem to be related to other disease processes of schizophrenia.

Effects of buprenorphine on a cecal ligation and puncture model in C57BL/6 mice.

Sepsis research relies heavily on animal models. One of the most frequently used models, cecal ligation and puncture (CLP), involves surgery, and animal use committees may require the use of analgesics after CLP. However, some analgesics are immunomodulatory and may affect research outcomes. In addition, both septic inflammation and responses to opioids may vary with the sex of the subject. Therefore, we investigated the effects of buprenorphine in inbred mice of both sexes undergoing CLP. We hypothesized that buprenorphine would not significantly change the outcome or patterns of inflammation in C57BL/6 mice after CLP. Male and female C57BL/6 mice underwent CLP surgery and were randomized into 2 groups to receive either buprenorphine or saline. Three-week survival studies were performed (n = 20 per group). Survival did not differ between groups of female mice, but male mice that received buprenorphine had decreased survival compared with that of controls. Reducing the dose of buprenorphine in male mice ameliorated the difference in survival. To examine inflammation, mice (n = 10 per group) were euthanized at 12, 24, or 48 h after CLP. Cell counts and cytokines were measured in the blood and peritoneal lavage fluid. In female and male C57BL/6 mice, buprenorphine treatment resulted in few differences in inflammatory parameters, although peripheral neutrophil counts were decreased transiently in male mice. The findings suggest that the effects of buprenorphine on sepsis models in C57BL/6 mice may be sex-specific. Consequently the use of analgesics must be assessed on a study-by-study basis, and investigators should define analgesic regimens when publishing sepsis studies.

Effects of short-term fasting in male Sprague-Dawley rats.

Fasting is a common procedure for animals in experiments. Although fasting may be necessary for scientific reasons, it should be minimized. In the current study, jugular-catheterized male Sprague-Dawley rats in metabolism cages were fasted for 0 to 24 h before measurement of various physiologic markers (serum chemistry, CBC analysis, serum corticosterone). When controlled for cohort, rats fasted for 6 and 16 h had significantly lower serum glucose than did nonfasted rats. Other values did not differ from controls. Only rats fasted for 24 h had elevated serum corticosterone levels. Therefore, fasting for as long as 16 h has fewer effects on rats that does fasting for 24 h. Fasting for 24 h or more therefore should receive appropriate consideration by both scientists and the IACUC in the experimental design and the animal-use protocol.

Effects of tramadol and buprenorphine on select immunologic factors in a cecal ligation and puncture model.

Sepsis research relies on animal models. The models that most closely resemble clinical disease, such as cecal ligation and puncture, require surgery. After surgery, analgesics may not be included in experimental protocols because of concern over effects on inflammatory responses. This often generates animal welfare controversies within institutions; however, there are no scientific studies directly addressing the effects of analgesics on surgical models of sepsis. The purpose of this study was to characterize the effects of opioids on key parameters used in sepsis research.Female ICR mice were divided into four treatment groups (Ringer's lactate solution, high- or low-dose tramadol,buprenorphine) for 3-week mortality studies (n = 12 per treatment). Experimental groups were then repeated, and mice were killed at 12, 24, and 48 h postsurgery for cell counts, differentials, and cytokine levels in blood, peritoneum, and airways. Mortality studies demonstrated no significant differences between controls and any treatment group. However,significant differences were noted between buprenorphine and high-dose tramadol, revealing more and later deaths with tramadol. For comparison of immune parameters, Mann-Whitney U or Student t test was performed, emphasizing comparisons between treatment and control. Although several results were significant, comparisons between control and any treatment group yielded no differences that remained consistently apparent during the observation period. Again,differences were observed between the treatments. The results suggest that judicious and limited use of some analgesics may not dramatically affect the outcome of similarly conducted cecal ligation and puncture studies when compared with those not using analgesics. However, when different analgesics are used, comparisons between studies may be complicated.

Modeling sepsis in the laboratory: merging sound science with animal well-being.

Despite impressive advances in biomedical research, few noteworthy breakthroughs have been made in the treatment of sepsis during the past several decades. This stalemate is primarily due to the intricate and heterogenic nature of the systemic immune responses characterized as the sepsis syndrome. In general, such complexity must be approached with in vivo models. Several animal models have been described, suggesting that none adequately address all of the pressing needs in sepsis research. The most clinically applicable models involve a localized infection, such as surgically induced polymicrobial sepsis, that gradually propagates a systemic immune response. Because relevant models must mimic a severe and chronic syndrome, animal well-being is often a concern in sepsis research. A balance between the needs of sepsis research and animal welfare can only be achieved through knowledge of the strengths and weaknesses of and alternatives to in vivo sepsis models.

Quantification, distribution, and possible source of bacterial biofilm in mouse automated watering systems.

The use of automated watering systems for providing drinking water to rodents has become commonplace in the research setting. Little is known regarding bacterial biofilm growth within the water piping attached to the racks (manifolds). The purposes of this project were to determine whether the mouse oral flora contributed to the aerobic bacterial component of the rack biofilm, quantify bacterial growth in rack manifolds over 6 mo, assess our rack sanitation practices, and quantify bacterial biofilm development within sections of the manifold. By using standard methods of bacterial identification, the aerobic oral flora of 8 strains and stocks of mice were determined on their arrival at our animal facility. Ten rack manifolds were sampled before, during, and after sanitation and monthly for 6 mo. Manifolds were evaluated for aerobic bacterial growth by culture on R2A and trypticase soy agar, in addition to bacterial ATP quantification by bioluminescence. In addition, 6 racks were sampled at 32 accessible sites for evaluation of biofilm distribution within the watering manifold. The identified aerobic bacteria in the oral flora were inconsistent with the bacteria from the manifold, suggesting that the mice do not contribute to the biofilm bacteria. Bacterial growth in manifolds increased while they were in service, with exponential growth of the biofilm from months 3 to 6 and a significant decrease after sanitization. Bacterial biofilm distribution was not significantly different across location quartiles of the rack manifold, but bacterial levels differed between the shelf pipe and connecting elbow pipes.

Echinoderms: their culture and bioactive compounds.

Of the five extant classes of echinoderms, it is the sea urchins (Echinoidea) and the sea cucumbers (Holothuroidea) that are both commercially fished and heavily overexploited. In sea urchins, it is the gonad of both males and females, normally referred to as'roe', that is a sought-after food. In the sea cucumber, the principal product is the boiled and dried body-wall or 'bêche-de-mer' for which there is an increasing demand. Many sea urchin and sea cucumber fisheries still have no management system or restrictions in place, and for those that do, the prognosis for catches to continue even at a reduced level is poor. Cultivation of these species increasingly becomes a necessity, both for stock enhancement programs and as a means to meet market demand. Sea urchin culture has been practised on a large scale in Japan for many decades, and effective methods for the culture and reseeding of species in these waters have been long established. Juvenile urchins are produced in their millions in state-sponsored hatcheries, for release to managed areas of seafloor. Outside of Japan, sea urchin cultivation is still a fairly recent practice, less than 10 years old, and largely still at a research level, although a range of species are now being produced in a variety of different culture systems. It is essential that the culture systems are adapted to be species-specific and meet with local environmental constraints. Sea cucumber cultivation originated in Japan in the 1930s and is now well established there and in China. Methods for mass cultivation of the tropical Holothuria scabra are now well established and practised in India, Australia, Indonesia, the Maldives and the Solomon Islands, with the focus of the research effort for both temperate and tropical species being centred on the production of juveniles in hatcheries for the restoration and enhancement of wild stocks. Like many other marine organisms, echinoderms have been, and continue to be, examined as a source of biologically active compounds with biomedical applications. Sea cucumber has been valued in Chinese medicine for hundreds of years as a cure for a wide variety of ailments. Some more recently isolated compounds, mainly from sea cucumbers and starfish, and including those with antitumour, antiviral, anticoagulant and antimicrobial activity are summarised below. When wild stocks decline, the demand created in the market place raises to the price of the product and, consequently, culturing is more likely to become viable economically. As this review shows, there have been dramatic advances in the culture methods of sea urchins and sea cucumbers in the last 10-15 years, to the extent that one can conclude that currently the major obstacles to successful cultivation are indeed economic rather than biological. Hence the future of the echinoculture industry is closely linked to that of the fisheries, whose fate will ultimately determine the market forces that will shape this growing industry.

Biosynthesis of eicosapentaenoic acid in the sea urchin Psammechinus miliaris.

The sea urchin Psammechinus miliaris (Gmelin) (Echinodermata: Echinoidea) was shown by using a deuterated tracer (D5-18:3n-3) and quantitation by negative chemical ionization gas chromatography-mass spectrometry to convert 18:3n-3 to 20:5n-3. The rate of conversion was very slow, corresponding to 0.09 microg/g tissue/mg 18:3n-3 eaten over 14 d. Deuterated arachidonic acid (D8-20:4n-6) was also included in the diet to give a measure of the relative amounts of diet eaten by the different animals. The recovery of this fatty acid in tissue lipids was 33.7% compared with only 0.95% recovery of D5-18:3n-3 and its anabolites, indicating that the majority of the D5-tracer was catabolized. Considerable elongation of D5-18:3n-3 into 20:3n-3 and a trace of 22:3n-3 was found, and these were accompanied by minor amounts of the intermediates 18:4n-3 and 20:4n-3. No deuterated 22:6n-3 was found.

Intraoral radiographic storage phosphor image mean pixel values and signal-to-noise ratio: effects of calibration.

OBJECTIVE: The DIGORA intraoral radiographic storage phosphor system needs to be calibrated before images are made. Calibration involves inputting of the maximum exposure to be used. This investigation studied the effects of different maximum exposure calibration settings on the mean pixel value for selected regions of interest and the signal-to-noise ratio for images of a test phantom. STUDY DESIGN: A dental phantom containing a step wedge made of different thicknesses of homogeneously radiopaque bone-equivalent material was imaged at 70 kVp with exposures ranging from 12.8 to 105.2 microC.kg-1. Images were displayed through use of imaging software, and a region of interest was set for each bone-step. The mean pixel values and their standard deviations were measured. RESULTS: Except for very low exposures (< 10% of the calibrated maximum), there was a linear relationship between exposure and the pixel values within the regions of interest irrespective of the calibrated maximum exposure. Low exposures resulted in underexposed low-contrast images. Low calibrated maximum exposures (< 54.5 microC.kg-1) resulted in low-density images with poor signal-to-noise ratios. CONCLUSIONS: Because of the very wide image latitude of the DIGORA system, loss of image quality was not observed as a result of adjustments in the calibration setting over the range of exposure commonly used in dental practice. The highest accepted exposure was limited by prior calibration; hence, if diligence is applied, patient exposure can be minimized without detriment to image quality.

Charge-coupled device panoramic radiography: effect of beam energy on radiation exposure.

OBJECTIVE: To determine the consequences for entrance exposure of varying the beam energy and operating current for panoramic radiography using a charge-coupled device receptor. MATERIAL AND METHODS: Images were made of a RANDO average man phantom (Alderson Research Laboratories, Stamford, CT) at kVcp settings of 60, 66, 70 and 80 and an mA of 2.0, 3.2, 6.4 and 10.0. The exposure cycle was set as recommended by the manufacturer at 17.6 s. Diagnostic image quality was rated by a panel of two oral and maxillofacial radiologists and one oral and maxillofacial pathologist. Entrance exposures were assessed using a 3 cc ionization chamber placed at the beam entry points while imaging the molar, premolar, and anterior teeth both using the DigiPan (Trophy Radiologie, Vincennes, France) CCD receptor and conventional T-Mat G film/Lanex Regular screens (Eastman Kodak, Rochester, NY, USA). RESULTS: Acceptable image quality was attained with combinations of 60 kVcp and 3.2, 6.4 or 10 mA, 70 kVcp and 2.0, 3.2 or 6.4 mA; at 80 kVcp irrespective of the mA it was unacceptable. The maximum reduction in entrance dose was 77%, averaged over the three sites, at 70 kVcp and 2 mA. CONCLUSION: The DigiPan receptor produces satisfactory images with saving in entry exposure saving of approximately 70% when compared with a conventional film/rare earth screen combination.

Tissue radiation dosages using the RVG-S with and without niobium filtration.

Tissue doses for a modified Rando head- and-neck phantom were measured for imaging with speed group E film with standardized aluminium filtration and the RVG-S both with and without added niobium filtration. Cylindrical holes drilled into the phantom's tissue-equivalent material permitted the placement of a small ionization chamber into anatomically correct sites representing the thyroid, parotid, submandibular and sublingual glands. To establish the necessary cone positions, angulations and time settings for each exposure, diagnostically acceptable images of six teeth, representative of different intraoral regions, were made for a DXXTR mannequin. Entrance and exit points were marked and transferred to the phantom to allow reproducible repeat exposures. The RVG-S provided reductions in average skin entrance dose of 31 per cent to 39 per cent with standard aluminium filtration and 51 per cent to 60 per cent with the addition of niobium filtration to attenuate the beam. While dose reductions relative to E-speed film usage were found for deep tissue sites, these were site and projection specific. The cumulative reduction from use of the RVG-S without niobium filtration was 32 per cent. It was 42 per cent with additional niobium filtration. It should be noted, however, that adding niobium filtration resulted in increased dosages to the deeper soft tissues such as the thyroid gland.