Constipation remains a frequent presentation to paediatricians, with significant health resource implications. We present a practical guide to the management of paediatric constipation and evaluate the current evidence for treatment regimens, to help the clinician in treating a condition that can be distressing and has a significant impact on affected families.

Since Huggins defined the androgen-sensitive nature of prostate cancer (PCa), suppression of systemic testosterone (T) has remained the most effective initial therapy for advanced disease although progression inevitably occurs. From the inception of clinical efforts to suppress androgen receptor (AR) signaling by reducing AR ligands, it was also recognized that administration of T in men with castration-resistant prostate cancer (CRPC) could result in substantial clinical responses. Data from preclinical models have reproducibly shown biphasic responses to T administration, with proliferation at low androgen concentrations and growth inhibition at supraphysiological T concentrations. Many questions regarding the biphasic response of PCa to androgen treatment remain, primarily regarding the mechanisms driving these responses and how best to exploit the biphasic phenomenon clinically. Here we review the preclinical and clinical data on high dose androgen growth repression and discuss cellular pathways and mechanisms likely to be involved in mediating this response. Although meaningful clinical responses have now been observed in men with PCa treated with high dose T, not all men respond, leading to questions regarding which tumor characteristics promote response or resistance, and highlighting the need for studies designed to determine the molecular mechanism(s) driving these responses and identify predictive biomarkers.

On examination she is found to be miserable. She is not clinically dehydrated and has a diffusely hyperaemic right cheek. On examination of her mouth you notice a raw area on her upper gums where two teeth are erupting. No other abnormal clinical signs are noted.

Clinical trials of high-dose androgen (HDA) therapy for prostate cancer (PC) have shown promising efficacy but are limited by lack of criteria to identify likely responders. To elucidate factors that govern the growth-repressive effects of HDAs, we applied an unbiased integrative approach using genetic screens and transcriptional profiling of PC cells with or without demonstrated phenotypic sensitivity to androgen-mediated growth repression. Through this comprehensive analysis, we identified genetic events and related signaling networks that determine the response to both HDA and androgen withdrawal. We applied these findings to develop a gene signature that may serve as an early indicator of treatment response and identify men with tumors that are amenable to HDA therapy.