Fetal membranes from term human pregnancies produce prostaglandins, and may respond to bacterial endotoxin or interleukin-1ß (IL-1ß) with increased prostaglandin E2 (PGE2) production. The effects of endotoxin persisted for up to 24 h, whereas those of IL-1ß were maximal 4-8 h after addition. The maximum levels of PGE2 (200-350 pg/ml) were similar in all experiments, and were independent of the stimulus used. Not all tissues responded to these stimuli; those which did not had basal levels of PGE2 production of 200-350 pg/ml, which was not further increased by endotoxin or IL-1ß. The basal production from these tissues was therefore similar to the maximal production from those tissues which responded to endotoxin or IL-1ß. The high basal production of PGE2 was attributed to prior in vivo activation of the membranes such that PGE2 synthesis could not be further stimulated in vitro. Overnight pretreatment with aspirin decreased basal PGE2 production from these activated membranes to <100 pg/ml/4 h during subsequent culture in aspirin-free medium. Both endotoxin and IL-1ß increased PGE2 production from the activated aspirin-pretreated membranes during this culture time, but this was transient as after 12 h of culture basal PGE2 production rose to over 200 pg/ml despite aspirin pretreatment.

Microcephalic primordial dwarfism (MPD) is a class of disorders characterized by intrauterine growth restriction (IUGR), impaired postnatal growth and microcephaly. Majewski osteodysplastic primordial dwarfism type II (MOPD II) is one of the more common conditions within this group. MOPD II is caused by truncating mutations in pericentrin (PCNT) and is inherited in an autosomal recessive manner. Detailed growth curves for length, weight, and OFC are presented here and derived from retrospective data from 26 individuals with MOPD II confirmed by molecular or functional studies. Severe pre-and postnatal growth failure is evident in MOPD II patients. The length, weight, and OFC at term (when corrected for gestational age) were À7.0, À3.9, and À4.6 standard deviation (SD) below the population mean and equivalent to the 50th centile of a 28-29-, 31-32-, and 30-31-week neonate, respectively. While at skeletal maturity, the height, weight, and OFC were À10.3, À14.3, and À8.5 SD below the population mean and equivalent to the size of 3-year 10-to 11-month-old, a 5-year 2-to 3-month-old, and 5-to 6-month-old, respectively. During childhood, MOPD II patients grow with slowed, but fairly constant growth velocities and show no evidence of any pubertal growth spurt. Treatment with human growth hormone (n ¼ 11) did not lead to any significant improvement in final stature. The growth charts presented here will be of assistance with diagnosis and management of MOPD II, and should have particular utility in nutritional management of MOPD II during infancy.

There is strong evidence for the involvement of inflammatory mediators such as interleukin (IL)-1 in the biochemical mechanisms of parturition. Therefore the effects of the IL-1 family (IL-1 (1 ng/ml), IL-1 (1 ng/ ml) and the IL-1 receptor antagonist (IL-1ra) (10 ng/ml)) on the regulation of prostaglandin synthesis in term human fetal membranes were investigated. It was found that, after 4 h of culture, IL-1 increased prostaglandin E 2 (PGE 2 ) output approximately twofold. This was associated with both a significant increase in cyclo-oxygenase-2 (COX-2) mRNA levels (approximately fourfold compared with control) and translocation of cytoplasmic phospholipase A 2 (cPLA 2 ) from the cytosol to the membrane fraction. IL-1 was less effective than IL-1 at stimulating PGE 2 production through similar mechanisms.IL-1ra had no effect on PGE 2 output. However, in combination treatments, IL-1ra did not inhibit IL-1 -or IL-1 -stimulated PGE 2 output, and increased PGE 2 production further compared with IL-1 alone. IL-1ra decreased IL-1 -induced COX-2 mRNA expression by about half and significantly increased cPLA 2 protein levels, as detected by immunoblotting, when used alone and together with IL-1 . These results suggest that IL-1ra has partial agonist properties when used together with IL-1 and IL-1 in fetal membranes by increasing cPLA 2 protein levels, which leads to an increase in the production of prostaglandins.

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Prevalence of endocrine sequelae in medulloblastoma survivors is high, and evolution of endocrine dysfunction can occur as late as 15 years from treatment completion; hence, long-term close monitoring of growth, puberty and gonadal function is essential.