How many cisplatin administration protocols does your department use?

The introduction, 30 years ago, of the co-administration of appropriate hydration and ensuring a diuresis occurs during the administration of cisplatin was important in its development, allowing clinically significant doses to be given with acceptable rates of toxicity. The clinical usage of cisplatin has increased and hydration protocols have been amended to increase patient comfort and reduce resource utilization. We suspected that this had led to unnecessary variations in practice both in clinical trials and subsequently in the clinic. Therefore, we reviewed practice in the Edinburgh Cancer Centre and discovered that 25 different hydration protocols were in use, with wide variation in dilution of cisplatin, total fluid administered, use of electrolyte (potassium and magnesium) supplementation and diuretics. These differences are a reflection of adoption of variations in hydration regimes published in pivotal clinical trials. A review of the available evidence relating to cisplatin associated hydration regimens was performed and recommendations will be made for the future design of evidence-based protocols.

Transfer and metabolism of prostaglandin E(2)in the dual perfused human placenta.

Prostaglandins (PGs) are potent paracrine hormones that are important for the control of several functions in the uterus and fetus during pregnancy and parturition. PGs are rapidly metabolized to inactive metabolites by prostaglandin dehydrogenase (PGDH). However, the regulation of transfer and metabolism of PGs across the placenta is not well understood. This study used an in vitro dual perfused human placental cotyledon preparation to examine the production of the potent vasoactive and myometrial stimulants PGE(2)and PGF(2alpha), transfer of PGs from the maternal to the fetal circulation and the metabolism of PGs by PGDH. Secretion of PGE(2)was greater into the fetal compared to the maternal circulation. PGE(2)output was higher than PGF(2alpha)and concentrations of PGE(2)and PGF(2alpha)metabolites (PGEM and PGFM) were greater in both fetal and maternal outputs when compared to the primary prostaglandins. Infusion of PGE(2)into the maternal circulation did not result in increased PGE(2)efflux but PGEM was output was increased, demonstrating a rapid and efficient metabolism by the placenta. There was no significant transfer of PGE(2)across to the fetal circulation, although there was some transfer but in the form of inactivated PGEM. There was no significant interconversion of PGE(2)to PGF(2alpha)by the 9-keto-reductase pathway. Expression of PGDH as detected by immunoblot was high in placenta. This PGDH was localized throughout the syncytiotrophoblast at the fetal-maternal interface and also in extravillous trophoblast cells. The presence of PGDH at this site acts to stabilize output of primary PG from the placenta and also as a barrier preventing transfer to the fetal circulation, resulting in the separation of PG homeostasis in the fetus and mother.