Challenges in managing proximal hypospadias: A 17-year single-center experience

BackgroundThere are only a few publications in the medical literature reporting on complication rates in proximal hypospadias surgery, particularly with regard to long-term follow-up.MethodsOver a 17.5-year period, we operated 100 patients with penoscrotal, scrotal and perineal hypospadias. Sixty-four had a single-stage repair, including 15 who received a buccal mucosa inlay “Snodgraft” repair. Thirty-six had a two-stage Bracka repair of which 19 received buccal or lower lip grafts and 17 had preputial grafts. Overall, 34 patients received buccal grafts. The median follow-up was eight years (range 1–16 years). Three patients were operated for residual chordee years later.ResultsUrethral fistulae occurred in a total of 26/100 (26.0%) cases, meatal stenosis in 16/100 (16.0%), wound breakdown in six (6.0%) and graft failure in one (1.0%). The fistula rate after the single-stage approach was 15/64 (23.4%), whereas it was 11/36 (30.6%) following two-stage repair (P = 0.4811).ConclusionsProximal hypospadias remains a challenging condition to treat. It is possible to perform a single-stage repair in 64.0% of cases. This brings down the median number of operations to only two. Lower lip grafts were used in 34.0% but are now used in redo-surgeries only. Our fistula rate was 26.0% but has decreased significantly in recent years.Level of evidenceLevel III.     

Prognostic significance of soluble fas and soluble fas ligand in serum of patients with complete hydatidiform moles

Citation Soni S, Rath G, Deval R, Salhan S, Mishra AKumar, Saxena S. Prognostic significance of soluble Fas and soluble Fas ligand in serum of patients with complete hydatidiform moles. Am J Reprod Immunol 2011; 66: 230–236 Problem Despite of advances in diagnosis and staging, the prognosis of hydatidiform mole (HM) remains intricate. HM possesses the substantial risk of developing persistent trophoblastic disease (PTD), which is considerably high for complete hydatidiform moles (CHMs). Significance of serum soluble Fas (sFas) and soluble FasL (sFasL) has been observed in various malignancies; however, there is no report till date on HM. Method of study The serum levels of sFas and sFasL were measured using enzyme‐linked immunosorbent assay in 62 patients with CHMs and 64 healthy controls. The protein concentrations were also correlated with clinicopathological parameters, β‐hCG level, and clinical outcome. Results The serum sFas and sFasL levels in patients with CHM were significantly higher than those in control group (mean ± SD: 703.497 ± 491.759 versus 348.141 ± 175.24; P < 0.004 and 31.17 ± 18.758 versus 18.802 ± 6.775; P < 0.0001, respectively). Patients who progressed to PTD demonstrated higher sFas and sFasL concentrations than those who regressed spontaneously (794.211 ± 415.892 versus 446.69 ± 161.382; P < 0.046 and 37.55 ± 20.337 versus 22.763 ± 6.52; P < 0.011, respectively). Furthermore, significant associations were observed among sFas, sFasL, and β‐hCG levels (P < 0.0001 for all associations). Conclusion Production of sFas and sFasL may play a crucial role in progression of CHM and may serve both as prognostic tool and therapeutic target in improving the clinical outcome.     

Recurrent hypoglycemia increases hypothalamic glucose phosphorylation activity in rats

The mechanisms underpinning impaired defensive counterregulatory responses to hypoglycemia that develop in some people with diabetes who suffer recurrent episodes of hypoglycemia are unknown. Previous work examining whether this is a consequence of increased glucose delivery to the hypothalamus, postulated to be the major hypoglycemia-sensing region, has been inconclusive. Here, we hypothesized instead that increased hypothalamic glucose phosphorylation, the first committed intracellular step in glucose metabolism, might develop following exposure to hypoglycemia. We anticipated that this adaptation might tend to preserve glucose flux during hypoglycemia, thus reducing detection of a falling glucose. We first validated a model of recurrent hypoglycemia in chronically catheterized (right jugular vein) rats receiving daily injections of insulin. We confirmed that this model of recurrent insulin-induced hypoglycemia results in impaired counterregulation, with responses of the key counterregulatory hormone, epinephrine, being suppressed significantly and progressively from the first day to the fourth day of insulin-induced hypoglycemia. In another cohort, we investigated the changes in brain glucose phosphorylation activity over 4 days of recurrent insulin-induced hypoglycemia. In keeping with our hypothesis, we found that recurrent hypoglycemia markedly and significantly increased hypothalamic glucose phosphorylation activity in a day-dependent fashion, with day 4 values 2.8 ± 0.6-fold higher than day 1 (P < .05), whereas there was no change in glucose phosphorylation activity in brain stem and frontal cortex. These findings suggest that the hypothalamus may adapt to recurrent hypoglycemia by increasing glucose phosphorylation; and we speculate that this metabolic adaptation may contribute, at least partly, to hypoglycemia-induced counterregulatory failure.     

GLUT-1 glucose transporters in the blood-brain barrier: differential phosphorylation

Glucose is the primary metabolic fuel for the mammalian brain, and a continuous supply is required to maintain normal CNS function. The transport of glucose across the blood-brain barrier (BBB) into the brain is mediated by the facilitative glucose transporter GLUT-1. Prior studies (Simpson et al. [2001] J Biol Chem 276:12725-12729) had revealed that the conformations of the GLUT-1 transporter were different in luminal (blood facing) and abluminal (brain facing) membranes of bovine cerebral endothelial cells, based on differential antibody recognition. This study has extended these observations and, by using a combination of 2D-PAGE/Western blotting and immunogold electron microscopy, determined that these different conformations are exhibited in vivo and arise from differential phosphorylation of GLUT-1 and not from alternative splicing or altered O- or N-linked glycosylation.     

Dysfunctional reward processing in male alcoholics: An ERP study during a gambling task

Objective

A dysfunctional neural reward system has been shown to be associated with alcoholism. The current study aims to examine reward processing in male alcoholics by using event-related potentials (ERPs) as well as behavioral measures of impulsivity and risk-taking.

Methods

Outcome-related negativity (ORN/N2) and positivity (ORP/P3) derived from a single outcome gambling task were analyzed using a mixed model procedure. Current density was compared across groups and outcomes using standardized low resolution electromagnetic tomography (sLORETA). Behavioral scores were also compared across groups. Correlations of ERP factors with behavioral and impulsivity factors were also analyzed.

Results

Alcoholics showed significantly lower amplitude than controls during all outcome conditions for the ORP component and decreased amplitude during the loss conditions for the ORN component. Within conditions, gain produced higher amplitudes than loss conditions. Topographically, both groups had an anterior focus during loss conditions and posterior maxima during gain conditions, especially for the ORN component. Decreased ORP current density at cingulate gyrus and less negative ORN current density at sensory and motor areas characterized the alcoholics. Alcoholics had higher levels of impulsivity and risk-taking features than controls.

Conclusions

Deficient outcome/reward processing and increased impulsivity and risk-taking observed in alcoholics may be at least partly due to reward deficiency and/or dysfunctional reward circuitry in the brain, suggesting that alcoholism can be considered as part of the cluster of the reward deficiency syndrome (RDS).     

The Kalgoorlie Otitis Media Research Project: rationale, methods, population characteristics and ethical considerations

Otitis media (OM) is one of the most common paediatric illnesses for which medical advice is sought in developed countries. Australian Aboriginal children suffer high rates of OM from early infancy. The resultant hearing loss can affect education and quality of life. As numerous factors contribute to the burden of OM, interventions aimed at reducing the impact of single risk factors are likely to fail. To identify key risk factors and understand how they interact in complex causal pathways, we followed 100 Aboriginal and 180 non-Aboriginal children from birth to age 2 years in a semi-arid zone of Western Australia. We collected demographic, obstetric, socio-economic and environmental data, breast milk once, and nasopharyngeal samples and saliva on seven occasions. Ear health was assessed by clinical examination, tympanometry, transient evoked otoacoustic emissions and audiometry. We considered the conduct of our study in relation to national ethical guidelines for research in Aboriginal and Torres Strait Islander health. After 1 year of community consultation, the study was endorsed by local committees and ethical approval granted. Fieldwork was tailored to minimise disruption to people's lives and we provided regular feedback to the community. We saw 81% of non-Aboriginal and 65% of Aboriginal children at age 12 months. OM was diagnosed on 55% and 26% of routine clinical examinations in Aboriginal and non-Aboriginal children respectively. Aboriginal mothers were younger and less educated, fewer were employed and they lived in more crowded conditions than non-Aboriginal mothers. Sixty-four per cent of Aboriginal and 40% of non-Aboriginal babies were exposed to environmental tobacco smoke. Early consultation, provision of a service while undertaking research, inclusion of Aboriginal people as active members of a research team and appropriate acknowledgement will assist in ensuring successful completion of the research.