Nancy R. Krieger

Early hernia repair in the premature infant: long-term follow-up.

The incidence of inguinal hernia and incarceration is high among premature infants. Optimal timing, anesthetic technique, and long-term results of hernia repair in hospitalized premature infants remain undefined. The authors reviewed the records of 52 consecutively treated premature infants who underwent bilateral inguinal herniorrhaphy under general anesthesia before discharge from the intensive care nursery. There were no significant differences in gestational age, birth weight, age and weight at time of surgery, or presence of preoperative apnea or bradycardia in between infants extubated within 24 hours and those intubated for more than 24 hours. Twenty-four infants (46%) were available for follow-up of 24 months or more (mean follow-up period, 57 months). One recurrence was identified, representing 4% of the long-term follow-up group and 2% of the initial population. Two patients had asymmetric testicular volumes suggestive of unilateral atrophy. The short- and long-term results suggest that repair under general anesthesia can be safely performed before discharge from the intensive care nursery.

Interferon-gamma and interleukin-10 messenger RNA are up-regulated after orthotopic liver transplantation in tolerant rats: Evidence for cytokine-mediated immune dysregulation*

BACKGROUND Immune regulation requires antigen recognition, signaling, activation, secretion of cytokines, and effector function by lymphocytes. Although there is redundancy in the activation and function of the immune response, some cytokines simultaneously promote and suppress different pathways of immunity. In the experiments reported here we compare cytokine gene expression within liver allografts from tolerant rats with normal and isografted liver tissue. We also compare the secretion of interferon-gamma (IFN-gamma) in the supernatant from mixed lymphocyte cultures by using peripheral blood lymphocytes stimulated against donor antigen. METHODS Orthotopic liver transplantations were performed using the cuff technique without hepatic artery revascularization. Nonisotopic in situ hybridization (ISH) was used to detect and localize messenger RNA to specific cells within tissue. Antisense DNA probes were generated to interleukin-2 (IL-2), IL-4, IL-10, and IFN-gamma. One-way mixed lymphocyte cultures were set up against irradiated donor splenocytes, and the supernatant was collected to measure IFN-gamma by enzyme-linked immunosorbent assay. RESULTS Expression of IFN-gamma and IL-10 was up-regulated in tolerant animals versus normal or isografted liver (p = 0.0002 and 0.0001, IFN-gamma and IL-10, respectively). In situ hybridization localized the expression of messenger RNA predominantly to the cytoplasm of the hepatocytes. Levels of IFN-gamma were higher in the supernatant from proliferating peripheral lymphocytes against donor antigen from tolerant animals versus naive control animals. CONCLUSIONS Expression of IFN-gamma and IL-10 is up-regulated in hepatocytes from allograft tissue after orthotopic liver transplantation. We believe that the up-regulation of IL-10 cross-regulates the effector function of IFN-gamma and supports cytokine-mediated immune dysregulation, which may be a mechanism of tolerance after orthotopic liver transplantation in rats.

Differential localization of allograft nitric oxide synthesis: comparison of liver and heart transplantation in the rat model

Nitric oxide (NO) is a free radical with a diversity of cellular origins and potential functions. Within the realm of solid organ transplantation, NO has been the focus of much attention. Discordant reports have documented both suppression and potentiation of the alloimmune response. In addition to questions regarding its functional role, little is known of the cellular origins of NO in acute rejection of vascularized allografts. To address this question, acute rejection models of rat heterotopic heart and orthotopic liver transplantation were chosen. When compared with naive controls and isografted animals, acute rejection in both heart and liver transplantation was associated with elevated systemic levels of the NO metabolite, nitrite. This was accompanied by increased graft content of iNOS protein as determined by immunoblot analysis of protein extracts. Expression of iNOS mRNA was localized with in situ hybridization. In both heart and liver transplantation, iNOS mRNA was found in the inflammatory infiltrate accompanying acute rejection. In addition, hepatocytes also expressed iNOS mRNA in the rejecting liver allograft. In contrast, cardiac myocytes in the rejecting heart allograft did not stain for iNOS mRNA. These results indicate that organ‐specific, differential cellular expression of iNOS occurs in the acutely rejecting allograft. Transcriptional regulation of iNOS may vary among various organs according to the local cellular milieu. In addition, there may be a variable allograft specific response to acute rejection which may modify the associated immunologic biology.

Power Doppler imaging of acute renal transplant rejection

We evaluated the usefulness of power Doppler imaging (PDI) in diagnosing acute renal‐transplant rejection.