Qualitative and quantitative assessment of sperm miRNAs identifies hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p as potential biomarkers of male infertility and sperm quality.

BACKGROUND: In contrast with the preceding stages of the germ cells, spermatozoa are unusually rich in small non-coding RNAs in comparison to the coding RNAs. These small RNAs may have had an essential role in the process of spermatogenesis or may have critical roles in the post-fertilization development. Sporadic efforts have identified a few differentially expressed miRNAs in infertile individuals, which do not replicate in other studies. METHODS: In order to identify miRNAs signatures of infertility or poor sperm quality, we compared miRNA differential expression data across nine datasets, followed by their analysis by real-time PCR in a case-control study. This was followed by the validation of potential biomarkers in yet another set of cases and controls. For this, total RNA was isolated from 161 sperm samples. miRNA expression levels in infertile cases and fertile controls were measured using TaqMan real-time PCR. Meta-analyses of two miRNAs (hsa-miR-9-3p and hsa-miR-122-5p) were performed using Comprehensive Meta-Analysis Software (version 2). All statistical analyses were performed with the help of GraphPad Prism Software (version 8). RESULTS: Literature search identified seven miRNAs (hsa-let-7a-5p, hsa-miR-9-3p, hsa-miR-22-5p, has-miR-30b-5p, hsa-miR-103-3p, hsa-miR-122-5p and hsa-miR-335-5p) showing consistent dysregulation in infertility across a minimum of four studies. In the discovery phase, six miRNAs showed strong association with infertility with four (hsa-miR-9-3p, hsa-miR-30b-5p, hsa-miR-103-3p and hsa-miR-122-5p) showing consistent differential regulation across all sub-groups. Receiver operating characteristic (ROC) curve analysis showed that the area under curve of > 0.75 was achieved by three (hsa-mir-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p) miRNAs. In the validation phase, these three miRNAs showed consistent association with infertility (hsa-mir-9-3p, hsa-miR-30b-5p, and hsa-miR-122-5p). Meta-analysis on hsa-miR-122-5p showed its significant quantitative association with infertility [Hedge's g = -2.428, p = 0.001 (Random effects)]. CONCLUSIONS: Three miRNAs (hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p) have strong linkage with infertility and a high potential as sperm quality biomarkers.

Polymorphisms in the HSF2, LRRC6, MEIG1 and PTIP genes correlate with sperm motility in idiopathic infertility.

The aim of this study was to investigate the association of 24 functionally important single nucleotide polymorphisms (SNPs) with male infertility. In this cross-sectional study, we genotyped 24 functionally important single nucleotide polymorphisms in 24 infertility candidate genes in 500 oligo-/astheno-/oligoastheno-/normo-zoospermic infertile men with idiopathic infertility. Sequenom iPlex gold assay was used for genotyping. Sperm count and motility were compared between prevalent genotypes at each test locus. We did not observe any significant difference in the average sperm count between the alternate genotypes for the loci in the KLK3, LRRC6, MEIG1, HSF2, ESR2 and PTIP genes. However, we observed a significant difference in sperm motility between the alternate genotypes for the loci in the LRRC6, MEIG1, HSF2 and PTIP genes. Polymorphisms in the LRRC6 (rs200321595), MEIG1 (rs150031795), HSF2 (rs143986686) and PTIP (rs61752013) genes show association with sperm motility.

SPATA16 promoter hypermethylation and downregulation in male infertility.

Spermatogenesis associated 16 (SPATA16) gene plays an important role in acrosome formation. In this study, we analysed SPATA16 promoter methylation in 29 oligozoospermic infertile and 16 normozoospermic fertile sperm samples and in testicular biopsy from 16 non-obstructive azoospermic and 2 obstructive azoospermic individuals. Next, we analysed SPATA16 level in sperm from 8 oligozoospermic infertile, 6 normozoospermic fertile, 9 IVF failed normozoospermic and 10 IVF successful normozoospermic samples by immunoblotting. This was followed by the analysis of SPATA16 expression in testicular biopsy from azoospermic individuals (n = 8) in comparison to normozoospermic individuals (n = 2). Oligozoospermic infertile sperm samples showed significantly higher methylation in the SPATA16 promoter region. Similarly, testicular biopsy from azoospermic men also showed significantly higher level of DNA methylation. Sub-group analysis of infertile sperm and testicular biopsy samples showed a direct correlation between DNA methylation and the degree of spermatogenic impairment. Oligozoospermic infertile samples and IVF failed samples showed reduced SPATA16 expression in comparison to normozoospermic fertile and IVF successful samples, respectively. Human biopsy analysis showed a significant decrease in SPATA16 expression in hypospermatogenesis, maturation arrest and Sertoli cell only syndrome. In conclusion, hypermethylation in SPATA16 promoter shows a highly significant correlation with infertility, which is consistent with its down-regulation in infertility.

Mutations in the desert hedgehog (DHH) gene in the disorders of sexual differentiation and male infertility.

PURPOSE: To identify the contribution of mutations in the Desert Hedgehog (DHH) gene to the disorders of sexual differentiation (DSD) and male infertility. METHODS: The study included a total 430 subjects, including 47 gonadal dysgenesis cases, 6 patients with undescended testis and infertility characterized by azoospermia, 125 infertile male patients characterized by oligoasthenozoospermia, 24 patients with oligoasthenoteratozoospermia, and 200 ethnically matched normozoospermic fertile men who had fathered a child in the last two years. Sequencing of the complete coding region of the DHH gene was undertaken to find its contribution to the DSD and male infertility. RESULTS: We observed four novel mutations in the DHH gene in the cases with different reproductive anomalies. A synonymous substitution, c. 543C>T (p.His181His) was observed in 6.6% oligoasthenozoospermic infertile males and 1.5% normozoospermic fertile control samples (RR = 4.4077, 95%CI 1.19-16.29). Another synonymous substitution, c.990G>A (p.Ala330Ala) was observed in an infertile patient with unilateral undescended testis (case #12). Insertion of G at c.1156insG (p.Arg385fs) was observed in a case with bilateral undescended testis and azoospermia (case #23). In gonadal dysgenesis category, two mutations, insertion of G at c.1156insG (p.Arg385fs) and c.997A>G (p.Thr333Ala) substitution were observed in one case (case #34). These mutations were completely absent in control samples. CONCLUSION: Mutations in the DHH gene impact reproduction with mild mutations affecting fertility, and severe or multiple mutations resulting in gonadal dysgenesis.

Assessment of long term outcomes after buccal mucosal graft urethroplasty: the impact of chronic kidney disease.

OBJECTIVES: To compare and assess various outcomes and success of buccal mucosal graft urethroplasty (BMGU) in patients with CKD versus patients having normal renal function. MATERIAL AND METHODS: This was a retrospective, single centre study, during period 2013 to 2017. Patients were grouped into two groups. Group 1 had patients with estimated Glomerular Filtration Rate (eGFR)>60mL/min/1.73m2 while group 2 had patients with eGFR <60mL/min/1.73m2. eGFR was calculated according to the MDRD equation. The two groups were compared with regard to various outcomes like length, location of stricture, technique of graft placement, intra-operative blood loss (haemoglobin drop), duration of hospital stay, post-operative complications and recurrence. RESULTS: A total of 223 patients were included in study with group 1 had 130 patients and group 2 had 93 patients. Mean age of patients with CKD were higher (47.49 years versus 29.13 years). The mean follow-up period was comparable between both groups (23.29 months and 22.54 months respectively). Patients with CKD had more post-operative Clavien Grade 2 or higher complications (p=0.01) and a greater recurrence rates (p<0.001) than in non-CKD patients. On multivariate analysis, age and CKD status was significant predictor of urethroplasty success (p=0.004) (OR= 14.98 (1.952-114.94, 95% CI). CONCLUSIONS: CKD patients are more prone to post-operative complications in terms of wound infection, graft uptake and graft failure and higher recurrence rates following BMGU.

Primary prostatic extra-gastrointestinal stromal tumor causing giant prostatomegaly.

Prostatic extra-gastrointestinal stromal tumors (E-GIST) are rare mesenchymal tumors with only 9-cases reported in the English literature so far. We herein describe a case of E-GIST causing massive enlargement of the prostate gland. A 55-year-old male was diagnosed with localized prostatic E-GIST causing massive prostatomegaly (1230 cc) during workup for lower urinary tract symptoms (LUTS). The patient was managed with Imatinib mesylate therapy as high anesthetic risks precluded surgery. Given the rarity, E-GISTs should be included in the differential diagnosis of patients presenting with LUTS as it may influence the treatment decisions.

Role of Percutaneous Nephrostomy in Bladder Carcinoma with Obstructive Uropathy: A Story Revisited.

OBJECTIVE: To evaluate the role of percutaneous nephrostomy (PCN) in patients of carcinoma bladder presenting with obstructive uropathy. MATERIAL AND METHODS: We evaluated medical records of 33 patients of bladder cancer with obstructive uropathy that presented to a tertiary care hospital in north India from January 2015 to December 2016. Outcome measures included technical success rates, change in blood urea and serum creatinine (measured on Day 1, 7, and 14); and complications of PCN according to Society of Interventional Radiology Guidelines for Percutaneous Nephrostomy. RESULTS: PCN was done in 30 patients. The mean age of patients was 51 years (range 42-67). 24 patients were male and 6 patients were female. The technical success rates for PCN placement were 93.33%. In 12 patients there was no improvement after PCN insertion. Improvement in clinical condition/kidney function occurred in 18 patients. Out of these 6 patients underwent radical cystectomy with ileal conduit formation and palliative radiotherapy/chemotherapy was given to 5 cases. In the remaining 7 patients, after an initial improvement that lasted for 2 weeks after PCN progressive renal dysfunction developed due to malignancy. Minor complications of PCN were seen in 16.6% of patients and major complications were seen in 10 % of cases. CONCLUSION: In selected patients with bladder carcinoma with obstructive uropathy, PCN insertion may improve kidney function tests to normal levels and enable them to receive tumor-specific curative/palliative treatment.

Are there any factors affecting the outcome of endoscopic sclerotherapy in filarial chyluria? A prospective study.

INTRODUCTION: Filarial chyluria is a frequent problem in India. While endoscopic therapy is the mainstay of treatment, it is not always successful. We aimed to determine parameters that affect outcomes of endoscopic sclerotherapy for filarial chyluria (FC). METHODS: Prospectively maintained data of FC patients who received endoscopic sclerotherapy between June 2011 and March 2015 were analyzed. Sclerotherapy included either povidone-iodine (0.1%) or silver nitrate (1%). The parameters recorded included clinical evaluation, urinary triglyceride (TG)/cholesterol, sclerotherapy treatment, and follow-up. RESULTS: One hundred and fifty-seven patients (male: female, 104:53) with a mean age (± standard deviation [SD]) 41.12 ± 13.68 years underwent endoscopic sclerotherapy. Grade II (68.88%) chyluria was a most common presentation followed by Grade III (25.69%). One hundred and forty-four patients responded whereas six patients failed to respond; another seven were lost to follow up, and twenty patients had recurrence. Overall success rate was 86.11%. Baseline urinary TG (mean ± SD) between success and recurrence group was 195.51 ± 164.73 mg/dl and 652.65 ± 62.55 mg/dl and cholesterol (mean ± SD) was 16.99 ± 10.08 mg/dl and 89.07 ± 39.87 mg/dl, respectively. Patient with urinary TGs >300 mg/dl and urinary cholesterol >30 mg/dl had 3.2 and 1.3 times higher chance to have recurrence after endoscopic sclerotherapy, respectively. Choice of sclerosing agent (silver nitrate 1% versus povidone-iodine 0.1%) had no difference in success rate, but silver nitrate had slightly higher complications rate (25% vs. 20%). A higher number of instillations (>3) was associated with better success rate. Majority of the complications were either Clavien Grade 1 or 2. CONCLUSIONS: The factors predicting recurrence were higher clinical grade, higher number of pretreatment courses, and high urinary TG and cholesterol.

Functional polymorphisms in the IL6 gene promoter and the risk of urinary bladder cancer in India.

BACKGROUND: Interleukin-6 is a multifunctional cytokine, which plays a key role in tumor proliferation and differentiation. Variations in its gene (IL6) sequence may affect the risk of developing various cancers, including urinary bladder cancer. The present study was done to find the association of functional polymorphisms in the IL6 promoter with urinary bladder cancer. MATERIALS AND METHODS: Single nucleotide polymorphisms were genotyped in histologically confirmed 232 cases of urinary bladder cancer and 250 healthy controls. The controls subjects were matched to the cases by age, sex, and ethnicity. Genotyping of the polymorphisms (-174G>C; -572G>C, -596A>G) was undertaken by direct DNA sequencing. The level of association between the genotypes and urinary bladder cancer risk was estimated by odds ratios and 95% confidence intervals generated by applying the chi-square test. Linkage disequilibrium (LD) between SNPs and haplotype analysis were performed using Haploview software. RESULT: Significantly higher number of smokers (p=0.047), tobacco chewers (p=<0.001) and those with non-vegetarian food habits (p=0.016) were seen in the case group. The distribution of genotypes at -174G>C locus differed significantly between cases and controls and the variant genotypes GC+CC were significantly rarer in the cases (p=0.00073; OR=0.52 95% CI 0.35-0.75). Variant genotypes (GC+CC) were more common in grade I than grade III tumors (p=0.032), further suggesting a protective effect. No LD was found between the SNPs; however, the frequency of haplotype AGC was significantly lesser in the cases than controls (p=0.0103), suggesting a protective effect. Genotype distribution at the other two loci (-572G>C and -596A>G) did not show association with bladder cancer. CONCLUSIONS: IL6 (-174G>C) substitution confers significant protection against the risk of urinary bladder cancer in the study population, while other substitutions in this gene (-572G>C and -596A>G) do not affect the risk. In general, there is a lack of studies on the cytokine gene polymorphisms in urinary bladder cancer.

Meatal Occlusive Disease in Adult Males: Are There Any Clinical Variations?

OBJECTIVE: The study aimed to document the types of meatal occlusive disease (MOD) in adult males in terms of its clinical presentation, management and prognosis. MATERIAL AND METHODS: Eighty-six adult males with MOD were assessed during the study period. The patients were divided into Group 1, having meatal opening that was occluded by flimsy adhesions (meatal synechia/adhesive type MOD), and Group 2 that included patients who had circumferential constriction of the meatus (meatal stenosis/constrictive type MOD). All patients underwent meatal dilatation up to 18 Fr followed by self-dilatation for 3 months with topical clobetasol for 4 weeks. Degree of discomfort during self-dilation, improvement in flow rate, International Prostate Symptom Score (IPSS score) and recurrences were recorded at pre-determined intervals. RESULTS: Twenty-eight patients had meatal synechia (Group 1) and 48 had meatal stenosis (Group 2). Discomfort during self-dilatation in Group 1 patients was significantly less; there was improvement in IPSS and peak flow rate (mean follow-up 26.8 months) as compared to Group 2. With dilation alone, no recurrence was noted in Group 1; however, Group 2 showed 62.8% recurrence indicating poor outcome in this subset of patients. CONCLUSION: MOD in adult males consists of 2 separate clinical entities with different therapeutic outcomes.

Status and Interrelationship of Zinc, Copper, Iron, Calcium and Selenium in Prostate Cancer.

Deficiency or excess of certain trace elements has been considered as risk factor for prostate cancer. This study was aimed to detect differential changes and mutual correlations of selected trace elements in prostate cancer tissue versus benign prostatic hyperplasia tissue. Zinc, copper, iron, calcium and selenium were analysed in histologically proven 15 prostate cancer tissues and 15 benign prostatic hyperplasia tissues using atomic absorption spectrophotometer. Unpaired two tailed t test/Mann-Whitney U test and Pearson correlation coefficient were used to compare the level of trace elements, elemental ratios and their interrelations. As compared to benign prostatic tissue, malignant prostatic tissue had significantly lower selenium (p = 0.038) and zinc (p = 0.043) concentrations, a lower zinc/iron ratio (p = 0.04) and positive correlation of selenium with zinc (r = 0.71, p = 0.02) and iron (r = 0.76, p = 0.009). Considerably divergent interrelationship of elements and elemental ratios in prostate cancer versus benign prostatic hyperplasia was noted. Understanding of differential elemental changes and their interdependence may be useful in defining the complex metabolic alterations in prostate carcinogenesis with potential for development of element based newer diagnostic, preventive and therapeutic strategies. Further studies may be needed to elucidate this complex relationship between trace elements and prostate carcinogenesis.

c.29C>T polymorphism in the transforming growth factor-ß1 (TGFB1) gene correlates with increased risk of urinary bladder cancer.

TGF-ß1 is a pleiotropic cytokine, which plays a dual role in tumor development. In the early stages, it inhibits the growth of tumor while in the late stages of carcinoma, it promotes tumor growth. The purpose of this study was to analyze the distribution of the TGFB1 gene polymorphisms between cases and controls so as to assess their correlation with bladder cancer risk. This study included 237 cases of urinary bladder cancer and 290 age matched controls from the same ethnic background. Three polymorphisms in the TGFB1 gene, c.29C>T (rs-1800470), c.74G>C (rs-1800471) and +140A>G (rs-13447341), were analyzed by direct DNA sequencing. Statistical analyses revealed no significant differences in the demographical data, except that the frequencies of smokers and non-vegetarians were higher in the cases. Eighty percent of the bladder cancer patients had superficial transitional cell carcinoma, and 53.16% and 26.31% of the patients were in grade I and grade II, respectively. We found that c.29C>T substitution increased the risk of bladder cancer significantly and recessive model of analysis was the best fitted model (p=0.004; OR=1.72 95% CI 1.18-2.50). A significantly higher risk in the recessive form was also suggested by co-dominant analysis showing that the homozygous form (TT) was a significant risk factor in comparison to CC and CT genotypes. The other two polymorphisms, c.74G>C (p=0.18, OR=0.67 95% CI 0.37-1.21) and +140A>G (p=0.416, OR=0.77 95% CI 0.41-1.45) did not affect the risk of urinary bladder cancer. In conclusion, we found that the TGFB1 c.29C>T substitution increases the risk of bladder cancer significantly while c.74G>C and +140A>G polymorphisms do not affect the risk.

A critical appraisal of complications of percutaneous nephrolithotomy in paediatric patients using adult instruments.

OBJECTIVE: To evaluate the complications (using the CROES Clavien scoring system) and various factors affecting them in children undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We analysed prospectively maintained data of paediatric PCNL (patients ≤17 years) from January 2008 to December 2012. Stone complexity was defined according to validated Guy's stone score (GSS). Procedures were performed in the prone position by experienced urologists. The tract was dilated (24-30F) under fluoroscopic guidance, and an adult rigid nephroscope complemented with a cystoscope/ureteroscope were used. Complications were recorded according to the CROES-Clavien score, recently defined by the Clinical Research Office of the Endourological Society (CROES) Study Group. RESULTS: The study group comprised 158 procedures performed in 153 children (98 boys and 55 girls), with a mean (range) age 10.03 ± 4.51 (2-17) years. The mean (range) stone burden was 376.68 ± 265.23 (150-2400) mm(2) . The distribution of cases according to the GSS was 31% grade I, 35.4% grade II, 19% grade III, and 14.6% grade IV. The stone-free rate of PCNL monotherapy was 85.4%, which increased to 93.7% after relook PCNL/extracorporeal shock wave lithotripsy. In all, 62 children (39.2%) had operative complications; 84% were minor, i.e. Clavien grade 1/2, and managed conservatively. Stone size, GSS, tract size, number of punctures and operation duration were significantly associated with complications on univariate analysis (P < 0.05). However, on multivariate logistic regression analysis, operation duration was the only independent risk factor associated with complications (95% confidence interval: 1.013-1.065, odds ratio = 1.04; P = 0.038). CONCLUSIONS: Percutaneous nephrolithotomy in children using adult instruments is an effective and safe procedure for managing simple as well as complex renal calculi. Assignment of specific Clavien scores to all possible PCNL complications by the CROES PCNL Study Group have improved precision in reporting complications in a standard objective format, including the minor ones. Such models are very useful for making inter-observer comparisons to obtain clinically relevant inferences. Mean operation duration is the only independent factor affecting complications of the procedure.

Dorsal onlay buccal mucosal graft urethroplasty in female urethral stricture disease: a single-center experience.

INTRODUCTION AND HYPOTHESIS: The aim of this report is to present our initial, short-term experience with dorsal onlay buccal mucosal graft urethroplasty (DBMGU) in women with urethral stricture. METHODS: Between May 2011 and April 2013, eight women with moderate to severe bothersome lower urinary tract symptoms due to mid- or distal urethral stricture underwent DBMGU. All women were evaluated preoperatively with the American Urological Association (AUA) symptom score, uroflowmetry with post-void residual volume (PVR) estimation, urodynamic study, calibration with 14 F catheter, and voiding cystourethrography. Postoperatively, the women were followed at regular intervals with AUA symptom score, uroflowmetry, and PVR estimation. Increase in AUA symptom score, maximum flow rate (Q(max)) < 12 ml/s, and failure to calibrate with 18 F catheter were considered as recurrence of the disease. RESULTS: The mean age of the patients was 40.6 years. The mean follow-up period was 14.8 months. All women voided successfully after catheter removal. One patient was lost to follow-up after 3 months. There was significant improvement in AUA symptom score and Q(max) and reduction in PVR (p < 0.0001) at 3, 6, and 9 months. Two women had recurrence of stricture at 12 months, while another had recurrence at 18 months which was treated by urethral dilatation followed by a self-dilatation protocol. The limitations of the study include the small number of cases with short follow-up. CONCLUSIONS: DBMGU is a simple and safe method of urethroplasty in women with unsatisfactory results. Large size studies with long-term follow-up are desirable to document the success rates.

Effect of phallic stretch on length of bulbous urethral stricture during retrograde urethrography.

OBJECTIVE: The purpose of this study was to evaluate the effect of phallic stretch on bulbous urethral stricture while performing retrograde urethrography (RUG). METHODS: Between July 2009 and June 2012, 197 adult males with stricture pattern on uroflowmetry underwent RUG. Two films were taken, first without (film A) and second after stretching the penis by about 5 cm (film B). 29 cases with proximal and distal bulbous strictures were included in the present analysis. The data recorded were stricture lengths in films A and B. RESULTS: 12 men had distal bulbous or penobulbous stricture (group 1) while 17 had stricture involving the proximal bulb (group 2). Mean stricture length in group 1 was 2.82 cm (range 1.2-4.2 cm) in film A and 4.59 cm (range 3.0-6.4 cm) in film B. In group 2 stricture length was 1.76 cm (range 1.0-2.3 cm) in film A and 1.79 cm (range 1.0-2.5 cm) in film B. The percentage change in stricture length on stretching was 38.48% (p = 0.0001) in group 1 and 1.67% (p = 0.8301) in group 2. CONCLUSIONS: The impact of phallic stretch on radiographic length during RUG was found to be significant in distal bulbous but not in proximal urethral stricture, which is important when interpreting the RUG and deciding the management of stricture.

Null genotypes at the GSTM1 and GSTT1 genes and the risk of benign prostatic hyperplasia: a case-control study and a meta-analysis.

BACKGROUND: Benign prostatic hyperplasia (BPH) is an age related non-malignant disease diagnosed as lower urinary tract symptoms and prostatic enlargement. Null genotypes in drug detoxification glutathione-S-transferase genes/enzymes, such as GSTT1 and GSTM1 have been reported to increase risk of several cancers including prostate. Meta-analysis on PC also suggested significant impact of GSTM1 null genotype but not that of GSTT1; however, BPH data have not been subjected to meta-analysis. METHODS: We investigated GSTT1 and GSTM1 genotypes in 429 subjects which included 244 BPH, 51 prostate cancer (PC) patients, and 134 control subjects to find if null genotype in any of the two genes increased the risk of BPH/PC. We also performed a quantitative meta-analysis on 888 BPH cases and 793 controls for GSTM1 and on 890 BPH cases and 793 controls for GSTT1 to assess overall consensus about the impact of null genotypes on BPH risk. RESULTS: We did not find any significant difference in the distribution of genotypes of either of the two genes between BPH/PC cases and controls; however, double deletion (GSTM1 null + GSTT1 null) increased BPH risk, significantly. Upon meta-analysis, null genotype of GSTM1 but not that of GSTT1 appeared to strongly affect BPH risk. CONCLUSIONS: In our population, null genotypes of either GSTM1 or GSTT1 do not appear to affect BPH risk; however, the double deletion was significantly associated with BPH. Meta-analysis suggested significant influence of GSTM1 null genotype but not that of GSTT1 on BPH risk.

Uroflowmetry nomograms for healthy children 5 to 15 years old.

PURPOSE: We determined flow rates and generated flow rate-voided volume nomograms based on healthy children 5 to 15 years old voiding spontaneously in their natural environment. MATERIALS AND METHODS: A total of 824 healthy school children of both genders were enrolled. A single uroflow record from each child was evaluated. A total of 103 children with a voided volume of less than 50 ml and/or a staccato/interrupted uroflow pattern were excluded, and 721 records were analyzed. Data were evaluated using several mathematical formulas and goodness of fit was determined. Linear regression analysis was used to generate nomograms. RESULTS: Flow rates and voided volumes increased with increasing age, with the effect being more pronounced in girls. No significant difference was noted in uroflow rates from 5 to 10 years, but significant differences (p <0.001) started appearing at 11 to 15 years. Also no significant difference was noted in uroflow rates among children 11 to 15 years. Therefore, 2 age groups were designated, with group 1 consisting of patients 5 to 10 years old and group 2 consisting of patients 11 to 15 years old. There were 222 boys and 122 girls in group 1 and 240 boys and 137 girls in group 2. In group 1 the maximum and average ± SD flow rates were 15.26 ± 4.54 ml per second and 7.68 ± 3.26 ml per second, respectively, for boys and 17.98 ± 6.06 ml per second and 9.19 ± 4.23 ml per second, respectively, for girls. In group 2 these rates were 22.50 ± 7.24 ml per second and 10.78 ± 4.03 ml per second, respectively, for boys and 27.16 ± 9.37 ml per second and 13.48 ± 5.21 ml per second, respectively, for girls. CONCLUSIONS: This large study, which expands the scant existing literature on uroflow parameters in healthy children, will hopefully promote wider application of uroflowmetry testing in the pediatric population.

Emphysematous Pyelonephritis With Scrotal Extension: An Unusual Case Presentation.

Emphysematous pyelonephritis (EPN) is a suppurative necrotizing form of renal infection with abscess and gas formation in the renal parenchyma and perirenal tissue. EPN with scrotal extension is rare; if not recognized and treated promptly, the clinical course can be severe and life-threatening. The most common causative organism is Escherichia coli and association with diabetes mellitus has been found in almost all cases. Prompt control of blood sugar and intravenous antibiotics are essential steps in management. Here, we report a rare form of extensive EPN extending from the right kidney to the scrotum retroperitoneally in a 47-year-old male with uncontrolled blood sugar. The patient was managed with a right percutaneous perinephric drain with right double J (DJ) stenting. His blood sugar was controlled by subcutaneous insulin. The patient was discharged on day 7 in satisfactory general condition with right percutaneous drainage and right DJ stent in situ.

Chemokine (CCR) and fractalkine (CX3CR) receptors and end stage renal disease.

OBJECTIVE AND DESIGN: Genetic polymorphisms of chemokines and their receptors were reported to be independent risk factors for inflammation associated disease. We explored the role of CCR5-Δ32, CCR5-G59029A, CX3CR1 V249I and T280M gene polymorphisms as susceptibility for end stage renal disease (ESRD). SUBJECTS AND METHODS: We genotyped 258 ESRD and 569 healthy controls by sequence-specific primers and RFLP and examined their association. RESULTS: There was significant difference in genotype frequencies of CCR5-G59029A (p = 0.005), and CX3CR1 V249I (p < 0.0001) between ESRD and controls. No homozygous individuals were observed for CCR5-Δ32. The haplotype analysis of all four studied genes reveled that haplotype +/A/T/I was more significant in patients and associated with higher risk (OR = 2.95) of ESRD. Further, the haplotype of CX3CR1 (T280M, V249I) gene showed 3.6-fold higher in an individual carrying T/I haplotype. No risk was seen for CCR5 haplotypes. CONCLUSIONS: These results highlight the role of CCR5 and CX3CR1 in ESRD.

Male infertility is not liked with HSF1, HSF2 and UBE2I gene polymorphisms among Indian subjects.

We analysed the polymorphisms at rs78202224 (C/A) for HSF1 gene, rs139496713 (C/T) and rs45504694 (C/A) for HSF2 gene and rs116868327 (G/A) for UBE2I gene in 547 infertile cases (non-obstructive azoospermia = 464, asthenozoospermia = 83) and 419 proven fertile controls of similar age group and ethnicity. SNP genotyping was done using AgenaMassARRY platform (Agena Bioscience, CA). Common, heterozygous, rare genotypes and allelic frequencies were analysed using dominant, recessive and co-dominant models. Data shows no significant association between HSF1, HSF2 polymorphisms and male infertility. However, under dominant (GG vs GA+AA) and co-dominanat (GG vs GA) model, polymorphism at the rs116868327 (G/A) locus in UBE2I gene was found to be linked with asthenozoospermia in males with a significant odd-ratio of 6.91 (confidence interval at 95% was 1.52-31.46; p=0.017). Moreover, frequency of rare allele was higher (2.4%) compared to controls (0.4%). Thus, this data showed a significant risk of developing asthenozoospermic condition in males (Odds ratio= 6.75; Confidence interval at 95%= 1.50-30.49; P= 0.018]. Hence, more number of genotyping studies along with the functional assay in multiple cohorts is needed to validate potential variants associated with male infertility.