Increased expression of endoarterial vascular cell adhesion molecule-1 mRNA in an experimental model of lung transplant rejection: diagnosis by pulmonary arterial biopsy.

BACKGROUND: Early detection of rejection after lung transplantation may prevent allograft failure. This study determines if mRNA from the cell adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in pulmonary endovascular tissue samples could be markers of early rejection. METHODS: Single left lung transplants were performed in five dogs. Each dog was treated for 2 weeks with immunosuppression, after which rejection was allowed to occur. Percutaneous biopsies from 2- to 3-mm distal branch pulmonary arteries were obtained in each dog from the normal and the transplanted lungs at the end of immunosuppression therapy and periodically (2-4 times) for 1 to 3 weeks until euthanasia. Levels of cell adhesion molecule mRNA in the biopsy samples were quantitated by reverse-transcriptase polymerase chain reaction and normalized to beta-actin mRNA levels. RESULTS: Between three and five pulmonary endoarterial biopsy samples were obtained from each lung at each catheterization procedure. There was a significant increase in VCAM-1 mRNA levels in the biopsies of the transplanted lungs (which were undergoing rejection) compared with the native right lungs in all dogs. Progressive increases in VCAM-1 mRNA were observed with longer rejection times. VCAM-1 mRNA changes were detected earlier than histologic changes of rejection. CONCLUSIONS: In pulmonary endoarterial biopsy samples obtained in a canine lung transplant model, there was a progressive increase in VCAM-1 mRNA levels with increasing rejection. Changes in VCAM-1 mRNA were observed earlier than histologic changes of rejection. VCAM-1 quantitation by endoarterial biopsy may be useful in surveillance and early diagnosis of rejection in patients who undergo lung transplantation.

Attitudes of neonatologists toward delivery room management of confirmed trisomy 18: potential factors influencing a changing dynamic.

OBJECTIVE: The objective of this study was to determine the attitude of neonatal providers toward delivery room resuscitation of an infant with confirmed trisomy 18 with known congenital heart disease at >/=36 weeks of gestation. METHODS: A multiple-choice questionnaire listing this clinical scenario was completed by neonatologists and fellows staffing level III NICUs. Potential factors influencing the decision to initiate resuscitation included maternal preference, neonatal condition at birth, obstetric care, and legal concerns. RESULTS: Fifty-four (76%) of 71 surveys were completed. Of respondents, 44% indicated that they would be willing to initiate resuscitation. Maternal preference (70%) was the primary reason to initiate resuscitation, with the appearance of the neonate in the delivery room (46%) and legal concerns (25%) as additional factors. CONCLUSIONS: Until recently, there was universal consensus that trisomy 18 was a lethal anomaly for which resuscitation in the delivery room was not indicated. These data indicate that more providers (44%) than anticipated would consider initiation of resuscitation for an infant with trisomy 18 even with congenital heart disease. We speculate that support for the best-interest standard for neonates is diminishing in favor of ceding without question to parental autonomy. This shift may have profound implications for ethical decisions in the NICU.

Clinical concepts of futility and ethically justified limits on neonatal care: a case presentation of an infant with Apgar scores of 0 at 1, 5, and 10 minutes.

Appropriate length of delivery room resuscitative efforts for infants born without signs of life is controversial. We present the case of a preterm infant with Apgar scores of 0 at 1, 5, and 10 minutes but with a recovered heartbeat at 15 minutes. Using the clinically relevant conceptions of the principle of futility, we examine the ethical justification for the successive decisions to initiate, continue, and ultimately limit care for this patient. This difficult case highlights the importance of understanding the ethical justification for clinical interventions that are made in the neonatal intensive care unit.