Use of holmium laser for urethral strictures in pediatrics: A prospective study.

INTRODUCTION: The management of urethral strictures is very challenging and requires the wide expertise of different treatment modalities ranging from endoscopic procedures to open surgical interventions. OBJECTIVE: To assess the effectiveness and complications of retrograde endoscopic holmium: yttrium-aluminum-garnet laser (Ho: YAG) urethrotomy (HLU) for the treatment of pediatric urethral strictures. PATIENTS AND METHODS: From January 2010 to January 2013, 29 male pediatric patients with a mean age of 5.9 years and primary urethral strictures 0.5-2 cm long were treated using HLU. The stricture length was <1 cm in 16 (55%) patients and >1 cm in 13 (45%). Fifteen (51.7%) patients had an anterior urethral stricture, while 14 (48.3%) had a posterior urethral stricture. No positive history was found in 14 (48.3%) patients for the stricture disease, while six (20.7%) had straddle trauma and nine (31%) had an iatrogenic stricture. All of the patients were pre-operatively investigated and at 3 and 6 months postoperation by uroflowmetry and voiding cystourethrography (VCUG). If there were suspicious voiding symptoms, selective uroflowmetry and VCUG were performed at 12 months postoperation. RESULTS: The mean operation time was 31.7 min (20-45 min). Twenty-three (79.3%) and 18 (62.1%) patients showed normal urethra on VCUG with improvement of symptoms at 3 and 6 months, respectively. Thus, recurrence was 37.9% after 6 months of follow-up. The mean pre-operative peak urinary flow rate (Qmax) was 6.47 ml/s. The mean postoperative Qmax at 3 and 6 months was 17.17 ml/s and 15.35 ml/s, respectively. The success rate and flowmetry results did not show any statistical significance in relation to site, length and cause of the strictures. The other 11 patients who failed to improve underwent repeated HLU sessions: 4/11 (36.3%) achieved successful outcomes. Among the seven patients with failed HLU for the second time, a third session was conducted. However, only one patient (14.2%) was cured, while open repair was needed for the remaining six. DISCUSSION: One study has previously been published on the management of pediatric urethral strictures using HLU. The present results are similar to short-term studies after a single session of visual internal urethrotomy using cold knife (VIU). In the present study, the length, location and cause of strictures did not significantly affect the results. However, the outcomes with strictures <1 cm were better than strictures >1 cm, although patients with strictures >2 cm were excluded. In the present study, the success rates among patients with second and third sessions of HLU were 36.3% and 14.2%, respectively. This was similar to other studies, which reported low success rate with the second session of VIU. The present study was limited by the relatively short period of follow-up and the small number of patients. However, it was the first prospective study evaluating HLU for pediatric strictures. The use of flowmetry and VCUG for evaluation of all patients added to the strength of the study. CONCLUSION: HLU can be safely used with good success rates for the treatment of primary urethral strictures (<2 cm) in children. Repeat HLU (more than twice) adds little to success.

Influencing factors for household water quality improvement in reducing diarrhoea in resource-limited areas

Background and Objectives: Water and sanitation are major public healthissues exacerbated by rapid population growth, limited resources, disasters andenvironmental depletion. This study was undertaken to study the influencing factorsfor household water quality improvement for reducing diarrhoea in resource‑limitedareas.Materials and Methods: Data were collected from articles and reviews from relevantrandomized controlled trials, new articles, systematic reviews and meta‑analysesfrom PubMed, World Health Organization (WHO), United Nations Children’s Fund(UNICEF) and WELL Resource Centre For Water, Sanitation And Environmental Health.Discussion: Water quality on diarrhoea prevention could be affected bycontamination during storage, collection and even at point‑of‑use. Point‑of‑use watertreatment (household‑based) is the most cost‑effective method for prevention ofdiarrhoea. Chemical disinfection, filtration, thermal disinfection, solar disinfectionand flocculation and disinfection are five most promising household water treatmentmethodologies for resource‑limited areas.Conclusion: Promoting household water treatment is most essential for preventingdiarrhoeal disease. In addition, the water should be of acceptable taste, appropriatefor emergency and non‑emergency use

Influencing factors for household water quality improvement in reducing diarrhoea in resource-limited areas.

BACKGROUND AND OBJECTIVES: Water and sanitation are major public health issues exacerbated by rapid population growth, limited resources, disasters and environmental depletion. This study was undertaken to study the influencing factors for household water quality improvement for reducing diarrhoea in resource-limited areas. MATERIALS AND METHODS: Data were collected from articles and reviews from relevant randomized controlled trials, new articles, systematic reviews and meta-analyses from PubMed, World Health Organization (WHO), United Nations Children's Fund (UNICEF) and WELL Resource Centre For Water, Sanitation And Environmental Health. DISCUSSION: Water quality on diarrhoea prevention could be affected by contamination during storage, collection and even at point-of-use. Point-of-use water treatment (household-based) is the most cost-effective method for prevention of diarrhoea. Chemical disinfection, filtration, thermal disinfection, solar disinfection and flocculation and disinfection are five most promising household water treatment methodologies for resource-limited areas. CONCLUSION: Promoting household water treatment is most essential for preventing diarrhoeal disease. In addition, the water should be of acceptable taste, appropriate for emergency and non-emergency use.

Comparative analysis of epitope recognition of glutamic acid decarboxylase (GAD) by autoantibodies from different autoimmune disorders.

Autoantibodies to GAD, an important marker of the autoimmune process in type I or insulin-dependent diabetes mellitus (IDDM), are also found in non-diabetic individuals with autoimmune polyendocrine syndrome type 1 (APS1), APS2, and stiff man syndrome (SMS). Most IDDM sera contain two distinct GAD antibody specificities, one of which targets an epitope region in the middle-third of GAD65 (IDDM-E1; amino acids 221-359) and one of which targets the carboxy-third of GAD65 (IDDM-E2; amino acids 453-569). Using 11 chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of IgG antibodies from an individual with APS2-like disease (b35, b78, and b96) and MoAbs from an IDDM patient (MICA-2, MICA-3, and MICA-4). Neither the APS2 IgG antibodies nor the IDDM MoAbs bind the amino-terminal third of GAD65, but instead target the carboxy-terminal two-thirds of GAD65. Amino acids 270-359 (IDDM-E1) are targeted by one APS2 IgG antibody and MICA-4, while two other APS2 IgG antibodies, MICA-2 and MICA-3, target amino acids 443-585 (IDDM-E2). Using GAD65/67 chimera that span the IDDM-E2 region, we found that MICA-2 binds amino acids 514-528 of GAD65, but two APS2 IgG antibodies require this region and amino acids 529-570. In contrast, the binding of MICA-3 requires two discontinuous amino acid segments of GAD65 (452-513 and 528-569), but not amino acids 514-528. These results indicate that there are both similarities and differences in the humoral response to GAD65 in APS2 and IDDM.

Glutamic acid decarboxylase autoantibodies in stiff-man syndrome and insulin-dependent diabetes mellitus exhibit similarities and differences in epitope recognition.

Glutamic acid decarboxylase (GAD) is an autoantigen in two autoimmune diseases, insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS). However, most individuals with one of these diseases do not have the other disease. Prior studies have suggested that the natures of the GAD Abs associated with each of these diseases are different, which may have implications for the autoimmune pathogenesis. We have compared the GAD autoantibody profile and have mapped GAD protein epitope regions in the two diseases using an immunoprecipitation assay with recombinant GAD 65 and GAD 67 proteins, GAD protein fragments, and synthetic GAD peptides, as well as chimeric GAD proteins. Our results indicate that individuals with SMS have GAD Abs in 100- to 500-fold higher titer than individuals with IDDM. The population of GAD Abs in SMS sera is quite complex and includes those that recognize at least three GAD 65 epitope regions located between amino acids 1-16, 188-442, and 442-563. These types of GAD Abs are not found in IDDM sera. All SMS sera also had Ab specificity that binds GAD 67 in a region highly homologous to amino acids 188-442 of GAD 65. In contrast to prior studies that used immunoblotting to measure GAD Abs, we find GAD Abs in SMS sera also target two conformation-dependent regions of GAD 65, one located in the middle and one near the C-terminus of the protein. These two regions of the GAD 65 protein are similar to regions targeted by GAD 65-specific Abs found in individuals with IDDM. These results indicate that although disease-specific epitopes may exist, there is also overlap in the humoral response between the two diseases.

Two distinct glutamic acid decarboxylase auto-antibody specificities in IDDM target different epitopes.

Although most individuals with insulin-dependent diabetes mellitus (IDDM) have autoantibodies to glutamic acid decarboxylase (GAD), antibodies to GAD are also present in some individuals with a low risk of developing diabetes. The GAD autoantibodies of IDDM are specific for the GAD65 isoform, do not bind denatured GAD protein, and target epitope(s) dependent on conformation of the protein. However, the IDDM epitopes have been difficult to further define because the antibodies do not bind GAD protein fragments or synthetic peptides. Since the GAD67 isoform is highly homologous to GAD65 but is usually not a target of the GAD autoantibodies in IDDM sera, we created six GAD65/GAD67 chimeric proteins to maintain the overall GAD protein conformation and used these chimeric proteins to map conformation-dependent epitopes of GAD65 targeted by IDDM sera. We find that the GAD binding present in most IDDM sera (n = 11 of 12) is composed of two distinct GAD antibody specificities that target different conformation-dependent regions of the GAD65 protein, one that is located between amino acids 240 and 435 (termed IDDM-E1) and one that is located between amino acids 451 and 570 (termed IDDM-E2). One IDDM serum (n = 1 of 12) bound only the IDDM-E1 region. Identification of epitopes targeted by IDDM sera may allow one to distinguish between GAD antibody-positive individuals at high and low risk of developing IDDM and to determine if differences in the autoimmune repertoire directed at GAD are present. The chimeric GAD65/GAD67 proteins may also be useful in designing GAD assays specific for IDDM.

Identification of glutamic acid decarboxylase autoantibody heterogeneity and epitope regions in type I diabetes.

Glutamic acid decarboxylase (GAD) is an autoantigen of the islet cell antibodies (ICAs) present in type I diabetes. GAD autoantibodies are also found in patients with stiffman syndrome and in certain ICA-positive individuals who rarely develop diabetes on long-term follow-up. This latter subset of ICA has been termed restricted or beta-cell-specific ICA because the antibodies react with only the beta-cells of the islet. By immunoprecipitation of recombinant GAD65 and GAD67 protein and protein fragments, 83% of sera from individuals with new-onset diabetes or prediabetes (n = 30) had GAD65 autoantibodies, but only 26% had GAD67 autoantibodies. In contrast, all restricted ICA sera (n = 6) had both GAD65 and GAD67 autoantibodies. In both types of sera, the binding of GAD67 autoantibodies could be blocked by preincubation of the serum with GAD65 and GAD67, but the binding of GAD65 autoantibodies could not be blocked by preincubation with GAD67. The titer of GAD65 autoantibodies was much higher in the restricted ICA sera (titer > 1:1,000) than in the sera from individuals with new-onset diabetes or prediabetes (titer < 1:100) and was reflected by the greater amount of GAD65 protein immunoprecipitated by restricted ICA sera (2.61 +/- 1.39 U) compared with sera from individuals with new-onset diabetes (0.51 +/- 0.34 U). The restricted ICA sera immunoprecipitated equimolar amounts of GAD65 protein fragments, suggesting a non-conformational or linear epitope; epitope mapping localized the major epitope region to amino acids 361-442 and a second minor epitope region to amino acids 1-195.(ABSTRACT TRUNCATED AT 250 WORDS)