Origin of an anomalous left coronary artery from a left hilar pulmonary artery.

Anomalous coronaries arising in nontruncal regions of the pulmonary artery are exceedingly rare. We report an autopsy case of an anomalous left coronary artery that arose from the distal pulmonary artery at the hilum of the left lung in an infant with complex congenital heart disease. To the best of our knowledge, this is the first such report. This previously unknown coronary malformation led to a fatal intraoperative complication during a pulmonary angioplasty procedure.

Does tight glucose control prevent myocardial injury and inflammation?

Hyperglycemia has been postulated to be cardiotoxic. We addressed the hypothesis that uncontrolled blood glucose induces myocardial damage in diabetic patients undergoing isolated coronary artery bypass graft surgery receiving continuous insulin infusion in the immediate postoperative period. Our primary aim was to assess the degree of tight glycemic control for each patient and to link the degree of glycemic control to intermediate outcome of myocardial damage. We prospectively enrolled 199 consecutive patients with diabetes undergoing isolated coronary artery bypass graft surgery from October 2003 through August 2005. Preoperative hemoglobin A1c and glucose measures were collected from the surgical admission. We measured biomarkers of myocardial damage (cardiac troponin I) and metabolic dysfunction (blood glucose and hemoglobin A1c) to identify a difference among patients under tight (90-100% of glucose measures < or = 150 mg/dL) or loose (<90%) glycemic control. All patients received continuous insulin infusion in the immediate postoperative period. We discovered 45.6% of the patients were in tight control. We found tight glycemic control resulted in no significant difference in troponin I release. Mean cardiac troponin I for tight and loose control was 4.9 and 8.5 (ng/mL), p value .3.We discovered patients varied with their degree of control, even with established protocols to maintain glucose levels within the normal range. We were unable to verify tight glycemic control compared to loose control was significantly associated with decreased cardiac troponin I release. Future studies are needed to evaluate the cardiotoxic mechanisms of hyperglycemia postulated in this study.

Restoration of adenosine deaminase-deficient human thymocyte development in vitro by inhibition of deoxynucleoside kinases.

Mutations in the gene encoding adenosine deaminase (ADA), a purine salvage enzyme, lead to immunodeficiency in humans. Although ADA deficiency has been analyzed in cell culture and murine models, information is lacking concerning its impact on the development of human thymocytes. We have used chimeric human/mouse fetal thymic organ culture to study ADA-deficient human thymocyte development in an "in vivo-like" environment where toxic metabolites accumulate in situ. Inhibition of ADA during human thymocyte development resulted in a severe reduction in cellular expansion as well as impaired differentiation, largely affecting mature thymocyte populations. Thymocyte differentiation was not blocked at a discrete stage; rather, the paucity of mature thymocytes was due to the induction of apoptosis as evidenced by activation of caspases and was accompanied by the accumulation of intracellular dATP. Inhibition of adenosine kinase and deoxycytidine kinase prevented the accumulation of dATP and restored thymocyte differentiation and proliferation. Our work reveals that multiple deoxynucleoside kinases are involved in the phosphorylation of deoxyadenosine when ADA is absent, and suggests an alternate therapeutic strategy for treatment of ADA-deficient patients.

Surgical management of esophageal perforation: role of esophageal conservation in delayed perforation.

Definitive repair of esophageal perforation is considered the preferred treatment for patients presenting early (<24 hours). However, the optimal management of delayed presentation (>24 hours) has not been well defined. This study examined the management of esophageal perforation and compared the outcomes of early versus delayed presentation. Records of patients admitted with the diagnosis of esophageal perforation were reviewed. Contrast studies were used to confirm the diagnosis in all cases. Patient demographics and outcome were analyzed to determine differences between early and delayed presentation. A total of 22 cases of esophageal perforation were identified (eight early vs 14 delayed presentations). Operative interventions included primary repair (four), reinforced repair (14) either with intercostal muscle or pleural flap, and a complete esophageal resection (one). Debridement and drainage without repair were done in two patients and a proximal intramural tear was treated with antibiotics and observation. Two patients died during hospitalization. All surviving patients had near-normal restoration of esophageal function. Follow-up at 3 years has shown minimal gastrointestinal problems. One patient required repeat esophageal dilatations and two patients underwent antireflux therapy. Esophageal repair should be considered in all cases of nonmalignant esophageal perforation and should not be influenced by the time of presentation.

Differential IL-7 responses in developing human thymocytes.

Interleukin (IL)-7 is a factor essential for mouse and human thymopoiesis. Mouse thymocytes have altered sensitivities to IL-7 at different developmental stages. CD4/CD8 double positive (DP) mouse thymocytes are shielded from the influence of IL-7 because of loss of CD127 (IL-7Ralpha). In this study, we assessed IL-7 receptor expression and IL-7 signaling in human thymocytes. We found human DP cells to be severely limited in their ability to phosphorylate STAT-5 in response to IL-7. The relative expression levels of the IL-7-inducible proteins Bcl-2 and Mcl-1 were also lower in human DP cells, consistent with a stage-specific decrease in IL-7 responsiveness. IL-7 responses were restored in a subset of cells that matured past the DP stage. Unlike the regulation of IL-7 signaling in mouse thymocytes, loss of IL-7 signaling in human DP cells was not due to absence of CD127, but instead correlated with downregulation of CD132 (common gamma chain).