Caudal anesthesia in pediatrics: an update.
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AIM: Caudal anesthesia is one of the most used-popular regional blocks in children. This technique is a useful adjunct during general anesthesia and for providing postoperative analgesia after infraumbilical operations. The quality and level of the caudal blockade is dependent on the dose, volume, and concentration of the injected drug. Although it is a versatile block, one of the major limitations of the single-injection technique is the relatively short duration of postoperative analgesia. The most frequently used method to further prolong postoperative analgesia following caudal block is to add different adjunct drugs to the local anesthetics solution. Only few studies evaluated quality and duration of caudal block against the volume of the local anaesthetic applied. After reviewing recent scientific literature, the authors compare the duration of postoperative analgesia in children scheduled for hypospadia repair when 2two different volumes and concentrations of a fixed dose of ropivacaine are used. METHODS: After informed parental consent, 30 children (ASA I, 1-5 years old) were enrolled in a multicentre, perspective, not randomized, observational study conducted in two 2 children hospitals. After premedication with midazolam, anesthesia was induced with thiopental and maintained with sevoflurane in oxygen/air. After induction, patients received a caudal blockade either with ropivacaine 0.375% at 0.5 mL/kg (Low Volume High Concentration Group, LVHC; n = 15), or ropivacaine 0.1% at 1.8 mLl/kg (High Volume Low Concentration Group, HVLC; n = 15). Surgery was allowed to begin 10ten minutes after performing the block. MAC-hour was calculated. In the recovery room, pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). In addition, the motor block was scored. After transferral to the ward, the patients were observed for 24 hours for signs of postoperative pain. The time period to first supplemental analgesic demand, i.e., from establishment of the block until the first registration of a CHEOPS score = or > 9, was considered the primary endpoint of the study. The time periods were compared using analysis of variance adjusted for age, weight and duration of surgical procedure as covariates. RESULTS: All patients were judged to have sufficient intraoperative analgesia, and none of them received additional analgesics intraoperatively. Patients' characteristics were similar, besides the age (32+/-10 vs 24 +/- 9 months; P < 0.05) and weigh (15.13 +/- 3.92 vs 11.93 +/- 1.83; P = 0.08). Analgesics were needed after 520 +/- 480 min in the LVHC and 952 +/- 506 min in the HVLC group (P < 0.05). Motor block was less in the HVLC group. CONCLUSIONS: In children undergoing hypospadia repair, caudal block with a ''high volume, low concentration'' regimen produces prolonged analgesia and less motor block, compared to a ''low volume, high concentration'' regimen. (+info)
Association of long polyglycine tracts (GGN repeats) in exon 1 of the androgen receptor gene with cryptorchidism and penile hypospadias in Iranian patients.
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Hypospadias (a urethral orifice located along the ventral side of the penis) and cryptorchidism (failure of the testes to descend into the scrotal sacs) are the 2 most common congenital malformations in males, affecting 0.3%-0.7% and 2%-4%, respectively, at birth. To study the association of CAG/GGN trinucleotide repeats in the androgen receptor gene with cryptorchidism and hypospadias in an Iranian population, we performed a case-control study of 76 cryptorchid and 92 hypospadiac (divided into subgroups of glanular, penile, and penoscrotal hypospadias) Iranian males. The length of the CAG/GGN repeat segment was evaluated by using polymerase chain reaction (PCR) sequencing in exon 1 and PCR-single-strand conformation polymorphism (PCR-SSCP) in exons 2-8. There were no significant differences in CAG lengths between the cases and controls, but GGN numbers were found to be significantly higher (median, 24 vs 22) among both subjects with penile hypospadias (P = .018) and those with a history of cryptorchidism (P = .001) compared with controls. In addition, the GGN numbers among subjects with penile hypospadias were significantly different compared with the 2 other subgroups of hypospadias (P = .001). We were able to identify 12 different CAG alleles and 8 different GGN alleles in the cryptorchid group. Although further studies are needed to elucidate the possible role of specific CAG/GGC combinations as a susceptible factor, our data suggested the possible association between polyglycin tract polymorphism in androgen receptor gene and cryptorchidism. (+info)
Mutation screening of BMP4, BMP7, HOXA4 and HOXB6 genes in Chinese patients with hypospadias.
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Hypospadias, one of the most common congenital abnormalities of the male external genitalia with elusive etiology, are caused by a defect in the normal development of the urethra, foreskin and ventral aspect of the penis. Evidences indicate that BMP4 and BMP7, two of those major factors in a signaling cascade involved in controlling the embryonic urethral development, play central roles in the normal development of the urethra, and that HOXA4 and HOXB6 play important roles in the development of skin in various tissues at the time course of the urethral development. We directly sequenced all these exons and exon-intron boundaries of the four genes in 90 unrelated Chinese patients with hypospadias. Thirteen different heterozygous nucleotide variations were identified for the first time in the four genes in 14 of 90 cases. Of the 13 variations, eight are missense: c.619C>G (p.H207D), c.668G>A (p.R223H), c.751C>T (p.H251Y) in BMP4; c.907C>T (p.R303C) in BMP7; c.385G>T (p.G129C), c.869C>G (p.S290C) in HOXA4; c.124C>A (p.P42T), c.367T>C (p.C123R) in HOXB6. None of these variations were found in 380 control chromosomes. Amino-acid sequence alignments showed most of these changed amino acids are conserved across various vertebrate species. In a word, these findings, together with the indicated roles of the four genes, imply that it should not be random events for so many nucleotide variations found in the present study. Further functional studies are required to make the associations clear between these variants and hypospadias. (+info)
Agricultural pesticide use and hypospadias in eastern Arkansas.
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INTRODUCTION: We assessed the relationship between hypospadias and proximity to agricultural pesticide applications using a GIS-based exposure method. METHODS: We obtained information for 354 cases of hypospadias born between 1998 and 2002 in eastern Arkansas; 727 controls were selected from birth certificates. We classified exposure on pounds of pesticides (estimated by crop type) applied or persisting within 500 m of each subject's home during gestational weeks 6 to 16. We restricted our analyses to 38 pesticides with some evidence of reproductive, developmental, estrogenic, and/or antiandrogenic effects. We estimated timing of pesticide applications using crop phenology and published records. RESULTS: Gestational age at birth [odds ratio (OR) = 0.91; 95% confidence interval (CI), 0.83-0.99], parity (OR = 0.79; 95% CI, 0.65-0.95), and delaying prenatal care until the third trimester (OR = 4.04; 95% CI, 1.46-11.23) were significantly associated with hypospadias. Risk of hypospadias increased by 8% for every 0.05-pound increase in estimated exposure to diclofop-methyl use (OR = 1.08; 95% CI, 1.01-1.15). Pesticide applications in aggregate (OR = 0.82; 95% CI, 0.70-0.96) and applications of alachlor (OR = 0.56; 95% CI, 0.35-0.89) and permethrin (OR = 0.37; 95% CI, 0.16-0.86) were negatively associated with hypospadias. CONCLUSIONS: Except for diclofop-methyl, we did not find evidence that estimated exposure to pesticides known to have reproductive, developmental, or endocrine-disrupting effects increases risk of hypospadias. Further research on the potential effects of exposure to diclofop-methyl is recommended. (+info)
Birth prevalence of cryptorchidism and hypospadias in northern England, 1993-2000.
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AIM: There is much debate as to whether the prevalence rates of cryptorchidism and hypospadias are increasing. To address this issue we investigated the birth prevalence of cryptorchidism and hypospadias in the northern region of England during the period 1993-2000. METHODS: Cases of cryptorchidism and hypospadias were identified from northern region hospital episodes statistics (HES). Trends in birth prevalence, based on the number of male live births, were assessed using linear regression. RESULTS: Prevalence was 7.6 per 1000 male live births for cryptorchidism and 3.1 per 1000 male live births for hypospadias. The orchidopexy rates for 0-4 year olds and 5-14 year olds were 1.8 and 0.8 per 1000 male population, respectively. The rates for hypospadias repair for 0-4 year olds and 5-14 year olds were 0.6 and 0.1 per 1000 male population, respectively. There was a statistically significant decreasing temporal trend for the corrective procedure in cryptorchidism of 0.1 per 1000 male population aged under 5 years per annum (95% confidence interval: -0.01 to -0.05, p<0.001), but no temporal change for the corrective procedure in hypospadias (p = 0.60). CONCLUSION: HES data were of high quality for the study period. There was no significant change in the prevalence of surgically corrected hypospadias. However, there was an apparent decline in the prevalence of surgically corrected cryptorchidism that may reflect a decrease in the prevalence of the condition or may be due to a decrease in the rate of surgical intervention. (+info)
Hypospadias: an update.
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Hypospadias is the most common congenital anomaly of the penis. The problem usually develops sporadically and without an obvious underlying cause. The ectopically positioned urethral meatus lies proximal to the normal site and on the ventral aspect of the penis, and in severe cases opens onto the scrotum or perineum. The foreskin on the ventral surface is deficient, while that on the dorsal surface is abundant, giving the appearance of a dorsal hood. Chordee is more common in severe cases. Cryptorchidism and inguinal hernia are the most common associated anomalies. The frequency of associated anomalies increases with the severity of hypospadias. For isolated anterior or middle hypospadias, laboratory studies are not usually necessary. Screening for urinary tract anomalies should be considered in patients with posterior hypospadias and in those with an anomaly of at least one additional organ system. The ideal age for surgical repair in a healthy child is between 6 and 12 months of age. Most cases can be repaired in a single operation and on an outpatient basis. Even patients with a less than perfect surgical result are usually able to enjoy a satisfactory sexual life. (+info)
FGFR2, FGF8, FGF10 and BMP7 as candidate genes for hypospadias.
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Hypospadias is a common malformation, which results from failure of urethral tube closure, and whose molecular mechanisms are still largely unknown. The normal genital development is orchestrated by the urethral plate epithelium (UPE), at the genital tubercle (GT), which has polarizing activity, controlling a network of epithelial-mesenchymal interactions, which, when disturbed, may lead to hypospadias. Homeobox proteins (HOXs), fibroblast growth factors (FGFs) and bone morphogenic proteins (BMPs) are essential in this process. Hypospadias in the Hoxa13 -/- mice occurs as a result of the combined loss of Fgf8 and Bmp7 expression in the UPE. In both Fgf10 and Fgfr2 deficient mutant hypospadic male mice, cell proliferation is arrested prematurely and the maturation of the urethral epithelium is disrupted. Fgf8, Fgf10, and their receptor Fgfr2 are downstream targets of androgens (AR) during external genital development, an important fact given the pivotal role of AR in male sex differentiation. Therefore, we examined FGFR2, FGF10, FGF8, and BMP7 as candidate genes for hypospadias. DNA from 60 boys with familial, isolated, hypospadias was screened for mutations in FGFR2, FGF10, FGF8, and BMP7 genes, using DHPLC and DNA sequence analysis. The sequence variations c.590C>G and c.582-62G>A in FGF8, and, c.550+27C>T, c.727+180T>G, c.830T>C (p.Me186Thr), and c.2454C>T in FGFR2 were found uniquely in patients with hypospadias, as compared with 96 controls. No genetic variant in the other genes was detected. These results indicate that mutations are rare in FGF8 and FGFR2 in hypospadias, but gene variants may influence the risk. (+info)
Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities.
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BACKGROUND: We have recently suggested that homozygosity for a specific 'AGATA' haplotype within a approximately 50 kb linkage disequilibrium (LD) block of the gene for estrogen receptor alpha (ESR1) may raise the susceptibility to cryptorchidism by enhancing estrogenic effects of environmental endocrine disruptors (EEDs). METHODS: Haplotype analysis of ESR1 was performed in 328 Japanese subjects, i.e. 70 patients with micropenis (MP), 43 patients with hypospadias (HS), 80 patients with spermatogenic failure (SF) and 135 control males. Genotyping was performed by the 5' nuclease assay. RESULTS: The LD block was identified in each of the patient groups and in the control males. The frequency of homozygotes for the specific 'AGATA' haplotype was markedly higher in the HS patients [P = 0.0000033, odds ratio [OR] = 11.26] and slightly higher in the MP patients (P = 0.034, OR = 3.64) than in the control males, and the 'AGATA' haplotype was strongly associated with HS (P = 0.0000022, OR = 11.26) and weakly associated with MP (P = 0.040, OR = 3.64) in a recessive mode. There was no significant difference between the SF patients and the control males. CONCLUSIONS: Our results support the hypothesis that homozygosity for the specific ESR1 'AGATA' haplotype may increase the susceptibility to the development of male genital abnormalities in response to estrogenic EEDs. (+info)