Theatre of paediatric surgery

In the 50 years since the first edition of this journal, operative paediatric surgery has undergone radical change. Many of the most common instruments are unchanged, both as a testament to their utility and in recognition of past surgeons remembered eponymously. Surrounding that basic core of instruments, theatre has changed radically as new tools and techniques have arisen. Surgeons have come down from their pedestals, recognising surgery as a team sport rather than a solo performance. More than half of the current paediatric surgical trainees are women, a higher proportion than in any other craft group of the Royal Australasian College of Surgeons. The appearance, and rapid development, of laparoscopy is to many observers the most notable change in surgery over the last 50 years. Placed in its context though, it is simply the most prominent example of a frameshift in surgical thinking. The patient as a whole is now the focus, rather than just the disease. Recent developments are as much about minimising harm to normal tissues as they are about extirpating pathology. As a surgical maxim, ‘Primum non nocere’ is even more in evidence in 2015 than it was in 1965.     

An association study of ABCG2 rs2231142 on the concentrations of allopurinol and its metabolites

ABCG2 is a gene that codes for the human breast cancer resistance protein (BCRP). It is established that rs2231142 G>T, a single nucleotide polymorphism of the ABCG2 gene, is associated with gout and poor response to allopurinol, a uric acid‐lowering agent used to treat this condition. It has also been suggested that oxypurinol, the primary active metabolite of allopurinol, is a substrate of the BCRP. We thus hypothesized that carrying the rs2231142 variant would be associated with decreased oxypurinol concentrations, which would explain the lower reduction in uric acid. We performed a cross‐sectional study to investigate the association between the ABCG2 rs2231142 variant and oxypurinol, allopurinol, and allopurinol riboside concentrations in 459 participants from the Montreal Heart Institute Hospital Cohort. Age, sex, weight, use of diuretics, and estimated glomerular filtration rate were all significantly associated with oxypurinol plasma concentration. No association was found between rs2231142 and oxypurinol, allopurinol and allopurinol riboside plasma concentrations. Rs2231142 was not significantly associated with daily allopurinol dose in the overall population, but an association was observed in men, with T carriers receiving higher doses. Our results do not support a major role of ABCG2 in the pharmacokinetics of allopurinol or its metabolites. The underlying mechanism of the association between rs2231142 and allopurinol efficacy requires further investigation.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

ABCG2 is a gene that codes for the human BCRP. It is established that rs2231142 G>T, a single nucleotide polymorphism of the ABCG2 gene, is associated with gout and poor response to allopurinol, a uric acid‐lowering agent used to treat this condition. It is not clear if pharmacokinetic changes are involved in the underlying mechanism of those observations.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study addressed whether the rs2231142 loss‐of‐function variant is associated with decreased oxypurinol concentrations.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Our results do not support a major role of ABCG2 in the pharmacokinetics of allopurinol or its metabolites.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Further investigations of the links between ABCG2 rs2231142 and the pharmacodynamics of allopurinol are needed.     

Giant cervical polyp: a case report and review of a rare entity

BACKGROUND: If cervical polyps are a common pathology in the female adult population, giant cervical polyps with a size greater than 4 cm are rare and until now only several cases have been described in literature. The size and the clinical presentation can mimic a cervical neoplasia. The management is surgical and can be conservative regarding to the benign pathological feature of this entity. CASE REPORT: We report the case of a giant cervical polyp of 5.5 cm occurring in a multiparous 47-year-old woman who clinically presented vaginal bleeding. The lesion was resected by electrosurgery with no recurrence 7 months after surgery. CONCLUSION: The diagnosis, management and outcome of this rare entity had been reviewed according to the literature.     

Uterine receptivity and cytokines: new concepts and new applications

The implantation process, currently thought to be the most critical step in achieving a successful early pregnancy, remains one of the most important unsolved processes in reproductive medicine. It depends on uterine-dependent and embryo-specific events, which need to be critically coordinated. Early embryo signaling following a maternal hormonal or cytokine-mediated preparation phase seems to be involved in stages immediately before, during and just after the apposition step to permit adequate proliferation of the stroma. Our objective is to develop guidelines and diagnostic tools pertinent to appreciate uterine receptivity. We will focus our attention on the uterine luminal environment at the time of oocyte retrieval and on the monitoring of the endometrium using three-dimensional ultrasound associated with digital technology and cytokine quantification by real-time PCR during the implantation window in an IVF/ICSI population. There is an accumulating body of data which strongly suggests that both implantation and uterine receptivity are controlled, primarily, though not exclusively, by locally acting growth factors and cytokines, some under steroid control. Some specific cytokines (IL-12, IL-15 and IL-18) in the luminal environment and in the endometrium allow a distinct pattern of abnormal uterine receptivity. The identification of these distinct patterns of abnormal uterine receptivity and of the mechanisms leading to the abnormal angiogenesis before implantation strongly suggest that no single therapeutic scheme can correct all cases of implantation failure and should be adapted for each patient especially in the case of unexplained infertility.     

Referatenteil

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Geschlechts-Krankheiten

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Hautkrankheiten

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Hautkrankheiten Akute und chronische Infektionskrankheiten

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