Nephrotoxicity issues of organophosphates.

Organophosphates are a large class of chemicals, initially invented in 1850 and since then they have been applied in numerous aspects of science to serve our purposes. Their mechanism of action in living organisms involves the irreversible inhibition of acetylcholinesterase, therefore they interfere with neuromuscular signal transmission. Due to the systematic and exaggerated use of these chemicals, there is massive exposure to them, hence there is great concern regarding the ramifications to all mammalian organisms. It has been widely accepted that over-exposure to organophosphates, has a deleterious impact on the renal tissue and subsequently on the renal function. Despite the significance of this global issue, limited knowledge exists, regarding the effect of these substances on our health. Therefore, new and extensive research is required to expand our knowledge and ensure proper guidance regarding the use of organophosphates as well the protection against their detrimental consequences. The aim of this review is to negotiate the effect of organophosphate exposure on renal tissue and kidney function.

Molecular and clinical aspects of embryotoxicity induced by acetylcholinesterase inhibitors.

Acetylcholinesterase inhibitors are widely used for a variety of medical, agricultural and public health purposes. Consequently, exposure is highly possible during lifetime. However, their systematic use raises concerns for the potential impact on the fetus and newborn since these substances may affect angiogenesis, the neonatal and maternal intensive care, neuroimmune function and response, mammary growth/lactation via cholinergic/non-cholinergic central and peripheral neuroendocrine pathways. New methodologies, neuroscientific technologies and research studies are needed to harness existing knowledge along with the proper management, availability for new acetylcholinesterase inhibitors, with stable pharmacodynamics and clinical outcomes.

The effect of mirabegron, used for overactive bladder treatment, on female sexual function: a prospective controlled study.

BACKGROUND: Αim of the study was to determine the effect of mirabegron, used for overactive bladder (OAB) treatment, on female sexual function. METHODS: Eighty five sexually active women suffering from overactive bladder were prospectively enrolled in this study. Females were divided into two groups. In Group A (control), 48 patients received no treatment and in Group B, 37 patients received mirabegron 50 mg/daily for 3 months. Patients were evaluated with FSFI-Gr at the beginning of the study and again after a period of 3 months. RESULTS: In Group B, there was a significant increase post-treatment compared to baseline (p < 0.001) in total FSFI (20.3 (3.8) to 26.6 (4.2)) and all domains (desire: 3.0 (1.2) to 4.8 (1.2)), arousal: 3.0 (0.8) to 4.8 (0.9), lubrication: 3.9 (1.1) to 4.8 (1.2), orgasm: 3.6 (0.8) to 4.8 (1.0), satisfaction: 3.2 (0.4) to 4.0 (0.8) and pain: 3.2 (0.8) to 4.4 (1.2)). In Group A, there were no statistically significant changes in pre- and post-observation values. CONCLUSIONS: This study is one of the few demonstrating that management of OAB with mirabegron improves female sexual function. TRIAL REGISTRATION: TRN ISRCTN17199301 , 20/10/2017, retrospectively registered.

Seasonal trends in the prevalence of hypospadias: Aetiological implications.

The aim of the present study was to examine the seasonality of hypospadias in Greece in an attempt to elucidate the aetiology. All boys born between 1991-1998, who underwent hypospadias repair at 'Aghia Sophia' Children's Hospital, Athens (n=542) were analysed. All Greek live-born males during the same period (population at risk; m=421,175) served as the controls. Seasonality by month of birth was evaluated with specific statistical tools. Meteorological parameters were also analysed. All tests yielded significant results, suggesting a simple harmonic prevalence pattern (highest/lowest: autumn, peak in October/spring, trough in April). Therefore, the first trimester of hypospadiac gestations coincides more frequently with winter. Meteorological parameters varied seasonally (maximal sunlight; air temperature in summer/minimal in winter, maximal rainfall in winter/minimal in summer) and were strongly associated pairwise. Hypospadiac birth prevalence follows a simple harmonic seasonal pattern and is associated with that of cryptorchidism in Greece. The coincidence of the first or third trimester of a potentially genetically influenced gestation with winter could lead to the phenotypic expression of hypospadias or cryptorchidism, respectively. The potential role of a cyclic-varied androgen-production stimulator, such as human chorionic gonadotrophin may be speculated. The seasonality of a common environmental factor acting directly/indirectly may contribute to these patterns, and possibly to the common pathogenesis of these congenital malformations.

Safety and Efficacy of Bipolar Versus Monopolar Transurethral Resection of the Prostate in Patients with Large Prostates or Severe Lower Urinary Tract Symptoms: Post Hoc Analysis of a European Multicenter Randomized Controlled Trial.

PURPOSE: We compare bipolar vs monopolar transurethral prostate resection safety/secondary outcomes including efficacy in patients with large prostate volume or severe lower urinary tract symptoms. MATERIALS AND METHODS: From July 2006 to June 2009 candidates for transurethral prostate resection were recruited at 4 centers, randomized 1:1 into monopolar/bipolar transurethral prostate resection arms and followed up to 36 months. Post hoc data analysis from patients with large prostate volume or severe lower urinary tract symptoms is presented. Patients with large prostate volume or severe lower urinary tract symptoms were defined as those with transrectal ultrasound based prostate volume greater than 80 ml or International Prostate Symptom Score greater than 19. Safety was estimated using sodium/hemoglobin changes immediately after surgery, complications during the early postoperative period (up to 6 weeks), and short-term (up to 12 months) and midterm (up to 36 months) followup. Secondary outcomes included, among others, efficacy quantified by changes in maximum urine flow rate, post-void residual urine volume and International Prostate Symptom Score compared with baseline. RESULTS: A total of 279 patients were randomized. Post hoc analysis of data from patients with a large prostate volume or severe lower urinary tract symptoms was based on analysis A-in 62 of 279 participants (22.3%) (monopolar transurethral prostate resection 32, bipolar transurethral prostate resection 30) or analysis B-in 126 of 279 participants (45.2%) (monopolar transurethral prostate resection 57, bipolar transurethral prostate resection 69). Mean (SD) prostate volume was 108.0 (25.9) ml for monopolar transurethral prostate resection and 108.9 (23.4) ml for bipolar transurethral prostate resection (p=0.756). Mean International Prostate Symptom Score was 25.0 (4.2) for monopolar transurethral prostate resection and 25.3 (3.7) for bipolar transurethral prostate resection (p=0.402). Neither safety nor any secondary outcome differed significantly between the arms throughout followup. The only exception was the decrease in sodium (analysis A), which was significantly greater after monopolar transurethral prostate resection (-4.2 vs -0.7 mmol/l, p=0.023) and did not translate into a significant difference in transurethral resection syndrome rates (monopolar transurethral prostate resection 1 of 32 vs bipolar transurethral prostate resection 0 of 30, p=1.000). CONCLUSIONS: Bipolar and monopolar transurethral prostate resection show similar safety/efficacy in these patient subpopulations.

Impact of varicocele on biological markers of gonadal function.

PURPOSE: The aim of this study is to evaluate the potential effect of varicocele in the hormonal and clinical profile of adolescents. METHODS: Twenty adolescents at Tanner stage 4-5 with left varicocele were studied and compared with a control group of 20 healthy adolescents. All patients underwent ultrasonographic testicular volumetry as well as hormonal evaluation of inhibin B, testosterone, baseline and gonadotropin-releasing hormone stimulated, follicle-stimulating hormone as well as luteinizing hormone. Statistical analysis was performed using the student's t test with p value <0.05 taken as statistical significant. RESULTS: Patients with varicocele showed reduced levels of inhibin B compared to controls and a significant reduction in the testicular volume on the affected side. The response of luteinizing hormone to gonadotropin-releasing hormone stimulation was significantly higher in the varicocele group compared to the control group. Furthermore a significant inverse relationship of inhibin B compared to follicle-stimulating hormone was noted. CONCLUSION: Serum inhibin B levels could represent a useful marker of Sertoli cell damage caused by varicocele.

Validation of revised Epstein's criteria for insignificant prostate cancer prediction in a Greek subpopulation.

BACKGROUND: Different treatment options for patients with prostate cancer (PCa) are applicable after stratifying patients according to various classification criteria. The purpose of our study is to evaluate the revised Epstein's criteria for insignificant PCa prediction in a Greek subpopulation. METHODS: During a 4-year-period, 172 Cretan patients were submitted to radical retropubic prostatectomy in our institution. 23 out of them met the revised Epstein's criteria for the presence of clinically insignificant PCa (clinical stage T1c, prostate specific antigen density < 0.15 ng/ml/g, absence of Gleason pattern 4-5, <3 positive biopsy cores, presence of <50% tumor per core) during pre-treatment evaluation and were retrospectively included in the study. Post-surgery outcomes were evaluated including pathological stage, surgical margins and Gleason score upgrade. RESULTS: Organ confined disease and insignificant PCa were predicted with a 74% and 31% accuracy, respectively. These figures are remarkably lower than those derived from similar studies worldwide. CONCLUSIONS: Due to the high variation in the revised Epstein's criteria prediction accuracy observed worldwide, the development and implementation of novel tools/nomograms with a greater predictive accuracy is still warranted. Hippokratia 2015, 19 (1): 30-33.

Systemic thrombolysis with the use of tenecteplase for segmental acute renal in-farction potentially associated with multiple thrombophilic gene polymorphisms.

BACKGROUND/AIM: The potential association of acute renal infarction with multiple thrombophilic gene polymorphisms and the experience of treatment with tenecteplase are described for the first time in the international literature. DESCRIPTION OF THE CASE: The case of a 50-year old male with segmental acute renal infarction potentially associated with multiple thrombophilic gene polymorphisms is presented. He was thrombolysed with a single intravenous bolus of tenecteplase in a weight-adjusted dose (0.53mg/Kg bodyweight). Within 30 minutes after drug administration, the patient's symptoms were completely relieved. Patient's clinical course was uneventful with an acceptable renal function outcome eight weeks post-treatment. The following gene polymorphisms were identified: G455A (b-fibrinogen); C677T; A1298C (methylenetetrahydropholate reductase); T196C (platelet glycoprotein IIIa); 4G/5G (plasminogen activator inhibitor-1). CONCLUSION: Tenecteplase is a safe and simple to use thrombolytic, with favourable pharmacokinetic profile, which might be useful if administered early, especially when local thrombolysis is impossible or unavailable and therefore warrants further investigation in clinical trials. Hippokratia 2014; 18 (1): 67-70.

Genetic analysis of the human Insulin-like 3 gene: absence of mutations in a Greek paediatric cohort with testicular maldescent.

This study investigated the hypothesis that genetic alterations of the human insulin-like 3 (INSL3) gene are associated with testicular maldescent (TMD). Genomic DNA was extracted and amplified from peripheral blood samples of 170 unrelated children with all possible phenotypical expressions of TMD and 50 volunteers with normal external genitalia from the general paediatric population (controls). PCR-single strand conformation polymorphism analysis was used to screen INSL3 gene for genetic variants. For rapid screening of a detected nonsilent genetic alteration, restriction assay using endonuclease Eag I was further employed. Products were analysed on 2% agarose gel and restriction patterns were visualised by ethidium bromide. Differences in genotype and allelic distributions of nonsilent genetic alterations were evaluated between (i) patients-controls, (ii) familial-sporadic, (iii) bilateral-unilateral and (iv) intra-abdominal-inguinal cases of TMD. No mutations were detected. Three common INSL3 gene polymorphisms (27G>A, 126G>A, 178G>A) unrelated to any particular phenotype of TMD were detected both in patients and controls. These results indicate that INSL3 gene mutations are not a common cause of TMD in the human.

The (TAAAA)n polymorphism of sex hormone-binding globulin gene is not associated with testicular maldescent.

The aim of this family-based study was to investigate the potential association/genetic linkage of the (TAAAA)n polymorphism of sex hormone-binding globulin gene proximal promoter with testicular maldescent (TMD). Genomic DNA was extracted from the peripheral blood of 487 subjects (174 index families): (i) 180 children with all phenotypes of TMD, (ii) 307 parents (156 mothers and 151 fathers). Conventional polymerase chain reaction amplification products were electrophoresed on 10% nondenaturating polyacrylamide gel and visualised by silver staining. After excluding ambiguous parental-child trios and most cases of index families with missing parental genotypes, 429 individuals were left for analysis: 138 completely typed nuclear families (five included a second affected child) and five child-parent couples (one parent missing). Eight fathers presented history of TMD, that is, a total of 156 cases with TMD were analysed. Alleles were analysed with the affected family-based control method and logistic regression-based extension of the transmission disequilibrium test for multiallelic loci. (ΤΑΑΑΑ)n polymorphism analysis revealed six alleles based on repeat numbers (n=5-10). No association/genetic linkage between the (TAAAA)n polymorphism and TMD was detected. Other factors should be investigated to potentially explain the genetic predisposition that seems to exist in at least a subgroup of these patients.

Screening for Y chromosome microdeletions in childhood: lack of evidence for a direct association with testicular maldescent.

The aim of the study was to investigate the hypothesis that Y chromosome microdeletions are directly implicated in testicular maldescent. Genomic DNA was extracted from the peripheral blood of 292 subjects. This population consisted of (i) 180 children with all phenotypes of isolated (non-syndromic) testicular maldescent from 174 index families, (ii) affected adult relatives available (n = 12) and (iii) 100 unrelated children with normal external genitalia (controls). The sequence-tagged site primer set and the conditions of conventional polymerase chain reaction amplification were based on the current laboratory guidelines for molecular diagnosis of Y chromosome microdeletions recommended by the European Academy of Andrology and the European Molecular Genetics Quality Network. Two multiplex reactions were designed to screen the regions of azoospermic factors a, b and c. Each multiplex reaction included adequate internal and external amplification controls. Amplification products were submitted to electrophoresis on 2% agarose gel impregnated with ethidium bromide dye solution for 80 volt-h and visualised under ultraviolet light. No microdeletions were detected in any subject. These results indicate that Y chromosome microdeletions are not directly implicated in the pathogenesis of testicular maldescent. Other factors should be investigated to potentially explain the genetic predisposition that seems to exist in at least a subgroup of these patients.

Tubeless percutaneous nephrolithotomy--the new standard of care?

PURPOSE: Traditionally the placement of a nephrostomy tube at the conclusion of percutaneous nephrolithotomy is considered the standard of care. However, the need for nephrostomy tube placement has been questioned by numerous authors. We evaluated the literature regarding tubeless percutaneous nephrolithotomy, and determined potential candidates for tubeless percutaneous nephrolithotomy and whether this procedure can be considered the new standard of care for complex stone removal. MATERIALS AND METHODS: A MEDLINE search was conducted between May 1997 and January 2010 to detect studies reporting tubeless percutaneous nephrolithotomy. "Nephrolithiasis," "percutaneous nephrolithotomy," "tubeless" and "lithotripsy" were used as medical subject headings (MeSH) key words. Additional citations were identified by reviewing the reference lists of the included articles. All relevant articles were reviewed for indications, outcomes and complications. RESULTS: The data obtained from 50 reports document comparable complication rates between tubeless and standard percutaneous nephrolithotomy. Tubeless percutaneous nephrolithotomy demonstrated advantages such as less pain, less debilitation, less costs and a shorter hospital stay. Mean stone-free rates for tubeless percutaneous nephrolithotomy were as high as 89%. CONCLUSIONS: Tubeless percutaneous nephrolithotomy appears to be safe and efficacious in uneventful procedures, in children, in obese patients, in simultaneous bilateral procedures, in supracostal access and in renal units with coexisting anatomical anomalies. Nephrostomy tube placement should still be considered in certain cases such as those with more than 2 nephrostomy access tracts, those necessitating a second look and those with intraoperative complications such as significant bleeding or collecting system perforation.

[Cryotherapy for renal tumors: current status and contemporary developments]. / Crioterapia de tumores renales: estado actual y desarrollos contemporáneos.

The proportion of renal tumors found incidentally dramatically increased in the past decade. More than half of them were diagnosed in patients over 70 years of age, a population with high associated comorbidity. Nephron-sparing minimally invasive surgical procedures are aimed at treating patients with small renal tumors and multiple comorbidities. Cryotherapy stands out among all other ablative procedures because of its better mid-term oncological outcome. A non-systematic review of the literature on cryotherapy as a treatment for renal tumors was made, analyzing its indications, actual and future application techniques, results, and complications.

[Urinary tract infections and Urolithiasis]. / Harnwegsinfektionen und Urolithiasis.

The classic "infection stone" struvite is formed as a result of metabolic activity of urease-positive bacteria from alkaline urine with pH-values above 7.5. Due to improved infection diagnostics and antibiotic therapy, the occurrence of infection-related urinary stones in the western industrialized world decreases, despite the generally increasing prevalence rates of urolithiasis in these societies. Struvite is often associated with other mineral phases. These accessory mineral phases could indicate other, non-infection-related causes of urinary stone formation. Thus, mineral analysis is always recommended. Struvite stones as well as struvite encrustations on urinary tract implants are characterized by rapid growth. The rapid growth-related embedding of urease-positive bacteria in the crystalline material makes the urinary stone a persistent source of recurrent urinary tract infections. According to the German Society of Urology guidelines on urolithiasis, a patient with the diagnosis "infection stone" should be assigned to the "high-risk" patient group. Complete stone and debris removal, as well as a special metaphylaxis strategy are required to initiate successful stone therapy.

Crioterapia de tumores renales: estado actual y desarrollos contemporáneos / Cryotherapy for renal tumors: Current status and contemporary developments

La proporción de tumores renales incidentales ha incrementado drásticamente en la ultima década, siendo diagnosticados en más de la mitad de los casos en pacientes mayores de 70 años, población con una alta comorbilidad asociada. Las técnicas ablativas mínimamente invasivas conservadoras de parénquima están destinadas a tratar a pacientes con tumores renales pequeños y múltiple comorbilidad. La crioterapia destaca sobre otras técnicas ablativas por sus mejores resultados oncológicos a medio plazo. Realizamos una revisión no sistemática de la literatura médica analizando la crioterapia como tratamiento de los tumores renales, analizando sus indicaciones, las técnicas de aplicación actuales y las perspectivas de futuro, los resultados y las complicaciones (AU)

The proportion of renal tumors found incidentally dramatically increased in the past decade. More than half of them were diagnosed in patients over 70 years of age, a population with high associated comorbidity. Nephron-sparing minimally invasive surgical procedures are aimed at treating patients with small renal tumors and multiple comorbidities. Cryotherapy stands out among all other ablative procedures because of its better mid-term oncological outcome. A non-systematic review of the literature on cryotherapy as a treatment for renal tumors was made, analyzing its indications, actual and future application techniques, results, and complications (AU)

Multiparametric comparison of cold knife tonsillectomy, radiofrequency excision and thermal welding tonsillectomy in children.

OBJECTIVE: This is a prospective study evaluating certain intraoperative and postoperative parameters, comparing the relatively new technique of thermal welding tonsillectomy with cold knife tonsillectomy, and radiofrequency excision in pediatric population. METHODS: Ninety children aged from 5 through 13 years were enrolled a randomized prospective trial comparing cold knife tonsillectomy, radiofrequency excision, and thermal welding tonsillectomy. Indications included recurrent acute tonsillitis and/or obstructive sleep apnea syndrome. All techniques were compared by means of length of surgery time, blood loss, postoperative bleeding and postoperative pain. RESULTS: Sixty-eight patients underwent tonsillectomy for obstructive sleep apnea, whereas 22 children underwent tonsillectomy due to recurrent acute tonsillitis. Median values of all variables tested, length of surgery time, blood loss, postoperative bleeding and postoperative pain, were found to differ significantly among the three surgical techniques (P<0.001). Particularly, a statistically significant higher median duration (P<0.001) and intraoperative blood loss (P<0.001), as well as, a statistically significant lower median pain score in each day tested (P<0.001) of the cold knife group, compared to each one of the other two groups, were found. Tissue welding and radiofrequency groups did not differ significantly in any aspect tested. CONCLUSIONS: Both thermal welding and radiofrequency excision techniques have shown comparable results regarding intraoperative blood loss, postoperative hemorrhage, and pain. Compared with cold knife tonsillectomy, welding and radiofrequency excision techniques were associated with less intraoperative blood loss and duration, though cold knife tonsillectomy seems to prevail over the two techniques in terms of the postoperative pain.

Colostomy type in anorectal malformations: 10-years experience.

AIM: The aim of this study was to evaluate the influence of colostomy type on morbidity during the treatment of anorectal malformations. METHODS: Sixty-eight infants (male: female ratio 1.3:1) with anorectal malformations that required colostomy were treated in our clinics during the period 1991-2001. Of these patients, 26 had received a loop colostomy: 14 of these underwent posterior sagittal anorectoplasty (PSARP) at the age of 9-12 months (Group A), and 12 underwent PSARP at the age of 2-4 months (Group B). Forty-two infants received a separated-stomas colostomy and underwent PSARP at the age of 9-12 months (Group C). The incidence of complications among groups was compared using the 2 sided Fisher's exact test. RESULTS: Eight cases from group A were complicated with prolapse of the stomas, perianal wound infection, pull-through dehiscence, and anal fibrotic stricture. The only complication observed in groups B and C was perianal wound infection, which occurred in 1 case from each group. A statistically significant difference was observed in the incidence of complication between groups A and C (p<0.001) and between groups A and B (p=0.014). The results from groups B and C did not differ significantly (p=0.398). When the cases complicated with colostomy prolapse were removed from the statistical analysis, groups A and C still differed significantly (p=0.001) but groups A and B did not (p=0.069). CONCLUSIONS: As the incidence of complications increases with time after a loop colostomy, we encourage either an early corrective procedure or the modification into separated-stomas colostomy (SSC) before PSARP is performed for those cases that would involve definitive surgery in late infancy.