Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial.

Down syndrome (DS) is the most common genetic cause of intellectual disability. The N-methyl-D-aspartate (NMDA) receptor uncompetitive antagonist, memantine hydrochloride (memantine), has been shown to improve learning/memory and rescue one form of hippocampus synaptic plasticity dysfunction in the best-studied mouse model of DS available, the Ts65Dn mouse. Given the status of memantine as a treatment for Alzheimer's disease (AD) approved by the Food and Drug Administration, the preclinical evidence of potential efficacy in Ts65Dn mice, and the favorable safety profile of memantine, we designed a study to investigate whether the findings in the mouse model could be translated to individuals with DS. In this pilot, proof-of-principle study we hypothesized that memantine therapy would improve test scores of young adults with DS on measures of episodic and spatial memory, which are generally considered to be hippocampus dependent. Accordingly, in this randomized, double-blind, placebo-controlled trial, we compared the effect of 16-week treatment with either memantine or placebo on cognitive and adaptive functions of 40 young adults with DS using a carefully selected set of neuropsychological outcome measures. Safety and tolerability were also monitored. Although no significant differences were observed between the memantine and placebo groups on the two primary outcome measures, we found a significant improvement in the memantine group in one of the secondary measures associated with the primary hypothesis. Only infrequent and mild adverse events were noted.

Impact of infants born at the threshold of viability on the neonatal mortality rate in Colorado.

OBJECTIVE: To determine the contribution of infants born at the threshold of viability (< 750 gm) on neonatal mortality in Colorado. STUDY DESIGN: For the period of January 1991 to December 1996, all Colorado live births who expired were evaluated for gestational age, birth weight, gender, hospital level of care, age at time of death, delivery room resuscitation, mechanical ventilation, medical and surgical complications, and serious malformations. RESULTS: Although infants weighing < 750 gm represent only 0.31% of all live births, they account for 46.3% of deaths. While those infants weighing < 500 gm and with a gestation of < 24 weeks almost always died (94.7%), the majority born in the 500- to 745-gm category (55.8%) survived. The vast majority (88.5%) of deaths occurred on the first day of life. A total of 38.4% of births in which the infant weighed < 750 gm occurred outside bona fide regional perinatal centers. CONCLUSION: Future attempts to reduce the Colorado neonatal mortality rate would best focus on the 500- to 750-gm weight group through the re-regionalization of high-risk perinatal care.

The application of hospice concepts to neonatal care.

Despite impressive improvements in outcome for infants cared for in neonatal intensive care units (NICUs), large tertiary-care referral units still admit a substantial number of infants who will not survive or, because of a predictably very poor outcome, should not be offered modern life-support techniques. Dealing with these infants can be extremely taxing on both the family and the staff. We have recently adapted the concepts first described in adult hospice care to the care of the dying neonate and his family. By providing a "Family Room" that is private yet close to the NICU and by training the staff in more supportive approaches toward these families, we have been able to deal with the problem of the dying newborn in a manner that has been beneficial to both families and staff.