Accuracy of glycemic measurements in the critically ill.

BACKGROUND: Recent evidence emphasizes the importance of maintaining normoglycemia in critically ill patients to reduce morbidity and mortality. Different analytical methods of varying accuracy exist for obtaining and measuring blood glucose in critically ill patients. The purpose of this study was to determine if there were differences in blood glucose values measured by whole blood capillary and arterial samples using three different bedside blood glucose meters and a blood gas analyzer as compared to a reference blood glucose analyzer. METHODS: Sixty subjects were recruited from a university hospital medical/surgical intensive care unit. Matching capillary and arterial samples were analyzed by a clinical blood glucose reference analyzer (YSI, Yellow Springs Instrument, Yellow Springs, OH) and three blood glucose meters (Lifescan [Milpitas, CA] SureStepFlexx, Roche [Indianapolis, IN] Accu-Chek Inform, and Abbott [Alameda, CA] FreeStyle). Additionally, the arterial samples were analyzed by a point-of-care blood gas analyzer (Chiron 865, Bayer, Tarrytown, NY). RESULTS: Data analysis included repeated-measures analysis of variance, Consensus Error Grid analysis, Bland-Altman plots, and numerical estimates of inaccuracy. With capillary samples there were high numbers of errors as compared to the reference instrument. Measurement of blood glucose with arterial samples demonstrates a higher degree of accuracy. With arterial samples, the Abbott FreeStyle blood glucose meter and the blood gas analyzer glucose exhibited the lowest median and mean relative absolute deviation. CONCLUSION: In critically ill adult patients, measurement of blood glucose using arterial samples is recommended. Using arterial blood, the Abbott FreeStyle blood glucose meter and the point-of-care blood gas analyzer (Bayer Chiron 865) were shown to be highly accurate instruments to measure arterial blood glucose.

Thrombin-thrombomodulin connects coagulation and fibrinolysis: more than an in vitro phenomenon.

Thrombin activatable fibrinolysis inhibitor (TAFI), when activated, forms a basic carboxypeptidase that can inhibit fibrinolysis. Potential physiologic activators include both thrombin and plasmin. In vitro, thrombomodulin and glycosaminoglycans increase the catalytic efficiency of TAFI activation by thrombin and plasmin, respectively. The most relevant (patho-) physiologic activator of TAFI has not been disclosed. Our purpose was to identify the physiologic activator of TAFI in vivo. Activation of protein C (a thrombin-thrombomodulin-dependent reaction), prothrombin, and plasminogen occurs during sepsis. Thus, a baboon model of Escherichia coli-induced sepsis, where multiple potential activators of TAFI are elaborated, was used to study TAFI activation. A monoclonal antibody (mAbTAFI/TM#16) specifically inhibiting thrombin-thrombomodulin-dependent activation of TAFI was used to assess the contribution of thrombin-thrombomodulin in TAFI activation in vivo. Coinfusion of mAbTAFI/TM#16 with a lethal dose of E coli prevented the complete consumption of TAFI observed without mAbTAFI/TM#16. The rate of fibrin degradation products formation is enhanced in septic baboons treated with the mAbTAFI/TM#16; therefore, TAFI activation appears to play a key role in the extent of fibrin(ogen) consumption during E coli challenge, and thrombin-thrombomodulin, in a baboon model of E coli-induced sepsis, appears to be the predominant activator of TAFI.

Porcine endogenous retroviral nucleic acid in peripheral tissues is associated with migration of porcine cells post islet transplant.

Porcine islets represent an alternative source of insulin-producing tissue, however, porcine endogenous retrovirus (PERV) remains a concern. In this study, SCID mice were transplanted with nonencapsulated (non-EC), microencapsulated (EC) or macroencapsulated (in a TheraCyte trade mark device) neonatal porcine islets (NPIs), and peripheral tissues were screened for presence of viral DNA and mRNA. To understand the role of an intact immune system in PERV incidence, mice with established NPI grafts were reconstituted with splenocytes. Peripheral tissues were screened for PERV and porcine DNA using PCR. Tissues with positive DNA were analyzed for PERV mRNA using RT-PCR. No significant difference was observed between non-EC and EC transplants regarding presence of PERV or porcine-specific DNA or mRNA. In reconstituted animals, little PERV or porcine DNA, and no PERV mRNA was detected. No PERV or porcine-specific DNA was observed in animals implanted with a TheraCyte trade mark device. In conclusion, an intact immune system significantly lowered the presence of PERV. Microencapsulation of islets did not alter PERV presence, however, macroencapsulation in the TheraCyte device did. Lower PERV incidence coincided with lower porcine DNA in peripheral tissues, linking the presence of PERV to migration of porcine cells.

Stem cell-based approaches to solving the problem of tissue supply for islet transplantation in type 1 diabetes.

Type 1 diabetes is a debilitating condition, affecting millions worldwide, that is characterized by the autoimmune destruction of insulin-producing pancreatic islets of Langerhans. Although exogenous insulin administration has traditionally been the mode of treatment for this disease, recent advancements in the transplantation of donor-derived insulin-producing cells have provided new hope for a cure. However, in order for islet transplantation to become a widely used technique, an alternative source of cells must be identified to supplement the limited supply currently available from cadaveric donor organs. Stem cells represent a promising solution to this problem, and current research is being aimed at the creation of islet-endocrine tissue from these undifferentiated cells. This review presents a summary of the research to date involving stem cells and cell replacement therapy for type 1 diabetes. The potential for the differentiation of embryonic stem (ES) cells to islet phenotype is discussed, as well as the possibility of identifying and exploiting a pancreatic progenitor/stem cell from the adult pancreas. The possibility of creating new islets from adult stem cells derived from other tissues, or directly form other terminally differentiated cell types is also addressed. Finally, a model for the isolation and maturation of islets from the neonatal porcine pancreas is discussed as evidence for the existence of an islet precursor cell in the pancreas.