Symposium on fresh whole blood for severe hemorrhagic shock: From in-hospital to far forward resuscitations

This report is prepared for The Hemostasis and Oxygenation Research (THOR) Network and based on presentations of invited THOR investigators. In order to make it available to a larger group of interested readers it has been agreed to publish the report in TRASCI, as a “what is happening?” in view of its importance and novelty. On June 14th 2011 the first symposium on fresh whole blood (FWB) was held in Bergen, Norway. THOR network leadership, which includes Tor Hervig, PhD, MD, Geir Strandenes, MD, Erling Bekkestad Rein, MD, and Philip C. Spinella, MD, organized the event. It was sponsored by the Royal Norwegian Navy Medical Service, Norwegian Armed Forces Medical Services and Caridian BCT. The objective of this meeting was to bring together investigators from around the world who are interested in analyzing the efficacy and safety of FWB for patients with severe traumatic hemorrhagic shock and to determine the initial steps in developing a research program in this area. The THOR network is specifically interested in determining if FWB can improve morbidity and mortality in combat casualties with life threatening hemorrhagic shock. A three-year research proposal has been developed by the THOR network to determine (1) if FWB donation adversely affects donor performance of combat related skills, (2) the optimal storage solution, temperature, and acceptable storage duration for FWB, (3) the logistics of providing FWB in a combat environment safely to include optimal transport and administration methods. The symposium speakers were tasked with reviewing current data on; coagulopathy associated with massive traumatic bleeding, immunology of transfusion, outcomes associated with FWB use, logistic and medical issues of the use of FWB in far forward situations, training required for medics on FWB collection and administration, the risks of FWB and stored blood components and methods to mitigate these risks. The meeting concluded with a discussion of the THOR network’s three-year research program.     

Focal myositis – A neurogenic phenomenon?

We report four cases of focal myositis. The patients, three men and one woman, had painful muscle hypertrophy, affecting four different sites. MRI confirmed the muscle enlargement and oedema. Electromyography revealed evidence of acute and chronic denervation in all four cases. Muscle biopsy was available in three and confirmed features suggestive of focal myositis. Based on our patient material, we suggest that chronic nerve irritation, such as compression, can lead to muscle hypertrophy which, when prolonged, provokes fibre necrosis and secondary inflammation. Our finding in four patients having hypertrophy involving four different sites, leads us further to suggest that this may be the common mechanism behind focal myositis.     

Mitochondrial DNA integrity is essential for mitochondrial maturation during differentiation of neural stem cells

Differentiation of neural stem cells (NSCs) involves the activation of aerobic metabolism, which is dependent on mitochondrial function. Here, we show that the differentiation of NSCs involves robust increases in mitochondrial mass, mitochondrial DNA (mtDNA) copy number, and respiration capacity. The increased respiration activity renders mtDNA vulnerable to oxidative damage, and NSCs defective for the mitochondrial 8-oxoguanine DNA glycosylase (OGG1) function accumulate mtDNA damage during the differentiation. The accumulated mtDNA damages in ogg1(-/-) cells inhibit the normal maturation of mitochondria that is manifested by reduced cellular levels of mitochondrial encoded complex proteins (complex I [cI], cIII, and cIV) with normal levels of the nuclear encoded cII present. The specific cI activity and inner membrane organization of respiratory complexes are similar in wt and ogg1(-/-) cells, inferring that mtDNA damage manifests itself as diminished mitochondrial biogenesis rather than the generation of dysfunctional mitochondria. Aerobic metabolism increases during differentiation in wild-type cells and to a lesser extent in ogg1(-/-) cells, whereas anaerobic rates of metabolism are constant and similar in both cell types. Our results demonstrate that mtDNA integrity is essential for effective mitochondrial maturation during NSC differentiation.     

Psychometric testing of a Norwegian version of the Premature Infant Pain Profile: an acute pain assessment tool. A clinical validation study

As neonates are submitted to pain, assessing the pain is crucial in effective pain control. The Premature Infant Pain Profile, an acute measurement tool combining physiological, behavioural and contextual indicators, was translated into Norwegian and tested clinically. The purpose was to establish construct validity, interrater reliability and internal consistency. In addition, the effect of sucrose as pain analgesia was tested in neonates >or= 36 weeks of gestational age. In a known-groups comparisons design with repeated measures, 111 consecutive neonates, preterm and term, were all observed at baseline, non-pain and pain event. Neonates in the neonatal unit received sucrose at pain event. A significant interaction effect of gestational age and events was found in the sucrose neonates. A significant interaction effect was detected from sucrose and event type for neonates from 36 weeks. The internal consistency of the six-item score was acceptable. A correlation coefficient of 0.89-0.97 was obtained for interrater reliability. The Norwegian version of the Premature Infant Pain Profile seems to be a reliable and valid instrument for pain assessment in neonates.     

The substrate-binding domain of 21-hydroxylase, the main autoantigen in autoimmune Addison's disease, is an immunodominant T cell epitope

The steroidogenic enzyme 21-hydroxylase (21OH) is the main autoantigen in autoimmune primary adrenal failure (Addison's disease). Autoantibodies against 21OH are immunological markers of an ongoing autoimmune process but are not directly involved in the tissue destruction. Autoreactive T cells are thought to mediate tissue damage, but the T cell antigen(s) has not been identified. To find out whether 21OH contains important immunodominant epitopes for T cells, we first immunized BALB/c and SJL inbred mouse strains with recombinant 21OH and showed that lymph node cells proliferated effectively following in vitro stimulation with recombinant 21OH (stimulation indices (SI) 20-40). We further synthesized a series of peptides based on 21OH with amino acid sequences with propensity to bind to major histocompatibility complex class II molecules. Only a few peptides could trigger lymphocytes of 21OH-primed mice to proliferate. One of these, 21OH (342-361), stimulated effectively 21OH-primed lymph node cells of SJL mice (SI = 4-8) and also, although to a lesser extent, of BALB/c mice (SI = 2.5). When SJL mice were immunized with 21OH (342-361), the immunizing peptide as well as peptide 21OH (346-361) triggered a significant proliferative response (SI = 24). A peptide from another part of 21OH, namely 21OH (191-202), did not stimulate the 21OH (342-361)-primed cells. Moreover, stimulation of lymph node cells of mice immunized with 21OH (342-361) with 21OH resulted in a significant proliferative response. We conclude that 21OH (342-361) is an immunodominant determinant for T cells in SJL and probably BALB/c mice. 21OH (342-361) corresponds to the substrate binding site of the enzyme. The p342-361 region may be involved in the pathogenesis of autoimmune adrenal failure in humans.