Induction of Transplant Tolerance with Immunodominant Allopeptide-pulsed Host Lymphoid and Myeloid Dendritic Cells

We have studied the effects of adoptive transfer of host thymic dendritic cells pulsed with immunodominant WF Class I peptide 5 (residues 93-109) on cardiac allograft survival in the WF-to-ACI rat combination. Our results showed that, whereas intrathymic inoculation of WF peptide 5-pulsed ACI thymic dendritic cells alone on day -7 did not prolong graft survival, similar treatment combined with 0.5 mL antilymphocyte serum (ALS) led to 100% permanent acceptance (> 200d) of donor-specific cardiac allografts. Extension of our study to systemic administration of peptide 5-pulsed host thymic dendritic cells confirmed that intravenous injection of peptide 5-pulsed self thymic dendritic cells combined with ALS transient immunosuppression resulted in 100% permanent donor-specific graft survival (> 200d). These results were reproducible in a clinically relevant model using intravenous injection of peptide-pulsed host myeloid dendritic cells. In contrast, thymectomy prior to adoptive transfer of peptide-pulsed host dendritic cells resulted in acute graft rejection at times equivalent to rejection in thymectomized controls. The long-term unresponsive recipients challenged with second-set grafts accepted permanently (> 100d) donor-type (WF) but not third party (Lewis) cardiac allografts. This study suggests that intravenous administration of genetically engineered dendritic cells expressing donor MHC molecules has the potential of inducing transplant tolerance.     

Prevalence and impact of extracolonic findings in patients undergoing CT colonography

BACKGROUND: CT colonography (virtual colonoscopy) is a new technique being offered to patients as a noninvasive method of imaging the colon. The aims of this study were to prospectively determine the prevalence of extracolonic findings in patients undergoing CT colonography, as well as to determine the clinical significance and consequences of these findings. METHODS: Two-hundred and fifty patients who were referred for colonoscopy for clinically indicated reasons underwent CT colonography using low-dose radiation (50 mAs) immediately prior to conventional colonoscopy. A single radiologist reviewed the CT images for extracolonic pathology, and findings were classified as having high, moderate, or low clinical significance. Electronic medical records were reviewed to assess what follow up diagnostic tests, if any, were performed. RESULTS: A total of 136 extracolonic findings were detected in 83 (33.2%) of the 250 patients. Of these 136 findings, 17 (12.5%) were highly significant, 53 (38.9%) were moderately significant, and 66 (48.5%) were of low significance. The most common highly significant lesions were solitary lung nodules in 3 patients, mesenteric lymphadenopathy in 3, adrenal masses in 2, low attenuation liver lesions consistent with metastases in 2, and bone metastases in 2 patients. Fourteen of the 17 (82.4%) highly significant findings were new findings, and in 11 the extracolonic abnormalities resulted in further diagnostic testing. None of the patients with moderate or low significance lesions underwent further testing. CONCLUSIONS: Low-dose CT colonography can detect highly significant extracolonic findings. Although extracolonic lesions were common, only a small proportion of patients required further diagnostic testing. Additional studies to determine the optimal radiation dose, cost-effectiveness, and legal implications of detecting extracolonic findings are warranted.     

Novel Infrastructure for Sepsis Biomarker Research in Critically Ill Neonates and Children

Introduction

Sepsis biomarker research requires an infrastructure to identify septic patients efficiently and to collect and store specimens properly. We developed a novel infrastructure to study biomarkers of sepsis in children.

Methods

Patients in pediatric and neonatal intensive care units were enrolled prospectively; enrollment information was stored in a secure, remotely accessible database. Researchers were notified of electronic medical record (EMR) orders for blood cultures (a surrogate for a diagnostic evaluation of suspected sepsis) by a page triggered by the order. Staff confirmed patient enrollment and remotely submitted an EMR order for collection of study specimens simultaneous with the blood culture. Specimens were processed and stored by a mobile clinical research unit.

Results

Over 2 years, 2029 patients were admitted; 138 were enrolled. Staff received pages for 95% of blood cultures collected from enrolled patients. The median time between the blood culture order and collection was 34 minutes (range 9–241). Study specimens were collected simultaneously with 41 blood cultures. The median times between specimen collection and storage for flow cytometry and cytokine analysis were 33 minutes (range 0–82) and 52 minutes (range 28–98), respectively.

Conclusion

This novel infrastructure facilitated prompt, proper collection and storage of specimens for sepsis biomarker analysis. Clin Trans Sci 2012; Volume #: 1–5