Polymorphonuclear (PMN) elastase in patients after severe traumatic brain injury.

BACKGROUND: Data on PNM elastase levels in cerebrospinal fluid following traumatic brain injury (TBI) in humans are not available in the literature. Therefore, the aim of this prospective study was to evaluate the dynamics of PMN elastase in the cerebrospinal fluid (CSF) of patients after TBI. METHODS: Patients suffering from isolated, closed TBI, presenting with an initial Glasgow coma score ≤ 8 and with intracerebral hemorrhage on the initial cranial computed tomography scan (performed within 90 min after TBI) were enrolled. CSF and blood samples were obtained immediately, 12 h, 24 h, 48 h, and 72 h after admission. ELISA testing was used to quantify the PMN elastase levels in CSF. In addition, the ratio of CSF albumin to serum albumin was calculated to evaluate the role of the blood-cerebrospinal fluid barrier (BCSFB). As controls, CSF samples were taken from patients receiving spinal anesthesia for elective orthopedic surgery of the lower extremity. RESULTS: Twenty-three patients meeting the inclusion criteria and ten control patients were enrolled. The PMN elastase showed a significant elevation at 48 and 72 h after TBI. When comparing the PMN elastase levels of patients with intact BCSFB to patients with defective BCSFB, there was no significant difference for the respective observation points. CONCLUSIONS: This is the first study to demonstrate that the PMN elastase levels in CSF significantly increased in the early posttraumatic phase (48 h and 72 h after TBI) in patients. The function of the BCSFB showed no significant influence on the PMN levels.

Significant Cytokine mRNA Expression Changes Immediately after Initiation of Cardiopulmonary Resuscitation.

INTRODUCTION: The purpose of this study was to evaluate immediate immunological changes following cardiopulmonary resuscitation (CPR). mRNA expression levels of selected immunomodulatory cytokines in out-of-hospital cardiac arrest (OHCA) survivors were detected and correlated to clinical parameter. METHODS: OHCA survivors with sustained unconsciousness after return of spontaneous circulation (ROSC) were included. PAXgene whole blood samples were drawn immediately after initiation of CPR and subsequently after 6 h, 12 h, 24 h, 48 h, and 72 h. TNF-alpha, IL-8, IL-10, and IL-1ra mRNA levels were quantified by RT-qPCR and compared to multiple organ failure, 30-day survival, and the induction of therapeutic hypothermia (TH). RESULTS: 25 patients (63 ± 15 years) were enrolled presenting a characteristic time-dependent cytokine profile in the early postresuscitation period. High initial TNF-alpha and IL-8 mRNA levels were followed by a significant decrease. IL-1ra mRNA levels significantly increased beginning after 6 h. Nonsurvivors showed significantly higher IL-8 mRNA levels immediately after CPR. TH induced significantly higher IL-1ra mRNA levels compared to normothermia. CONCLUSION: Significant mRNA cytokine expression changes are already detectable immediately after initiation of CPR. These expressional changes are significantly different depending on 30-day survival. TH seems to attenuate proinflammatory immune reaction by a significant increase of IL-1ra mRNA levels. This trial is registered with DRKS00012940.

Genome-Wide Changes in Peripheral Gene Expression following Sports-Related Concussion.

We conducted a prospective study to identify genome-wide changes in peripheral gene expression before and after sports-related concussion (SRC). A total of 253 collegiate contact athletes underwent collection of peripheral blood mononuclear cells (PBMCs) before the sport season (baseline). Sixteen athletes who subsequently developed an SRC, along with 16 non-concussed teammate controls, underwent repeat collection of PBMCs within 6 h of injury (acutely). Concussed athletes underwent additional sample collection at 7 days post-injury (sub-acutely). Messenger RNA (mRNA) expression at baseline was compared with mRNA expression acutely and sub-acutely post-SRC. To estimate the contribution of physical exertion to gene changes, baseline samples from athletes who subsequently developed an SRC were compared with samples from uninjured teammate controls collected at the acute time-point. Clinical outcome was determined by changes in post-concussive symptoms, postural stability, and cognition from baseline to the sub-acute time-point. SRC athletes had significant changes in mRNA expression at both the acute and sub-acute time-points. There were no significant expression changes among controls. Acute transcriptional changes centered on interleukins 6 and 12, toll-like receptor 4, and NF-κB. Sub-acute gene expression changes centered on NF-κB, follicle stimulating hormone, chorionic gonadotropin, and protein kinase catalytic subunit. All SRC athletes were clinically back to baseline by Day 7. In conclusion, acute post-SRC transcriptional changes reflect regulation of the innate immune response and the transition to adaptive immunity. By 7 days, transcriptional activity is centered on regulating the hypothalamic-pituitary-adrenal axis. Future efforts to compare expressional changes in fully recovered athletes with those who do not recover from SRC could suggest putative targets for therapeutic intervention.

Use of computed tomography and mechanical CPR in cardiac arrest to confirm pulmonary embolism: a case study.

Precise therapeutic decision-making is vital in managing out-of-hospital cardiac arrest. We present an interesting approach where suspected pulmonary embolism could be confirmed by early computed tomography in cardiac arrest. Chest compressions were performed automatically by mechanical devices also during the acquisition of computed tomography data and subsequent thrombolysis.

Early Dynamics of Cerebrospinal CD14+ Monocytes and CD15+ Granulocytes in Patients after Severe Traumatic Brain Injury: A Cohort Study.

In traumatic brain injury (TBI) the analysis of neuroinflammatory mechanisms gained increasing interest. In this context certain immunocompetent cells might play an important role. Interestingly, in the actual literature there exist only a few studies focusing on the role of monocytes and granulocytes in TBI patients. In this regard it has recently reported that the choroid plexus represents an early, selective barrier for leukocytes after brain injury. Therefore the aim of this study was to evaluate the very early dynamics of CD14+ monocytes and CD15+ granulocyte in CSF of patients following severe TBI with regard to the integrity of the BBB. Cytometric flow analysis was performed to analyze the CD14+ monocyte and CD15+ granulocyte population in CSF of TBI patients. The ratio of CSF and serum albumin as a measure for the BBB's integrity was assessed in parallel. CSF samples of patients receiving lumbar puncture for elective surgery were obtained as controls. Overall 15 patients following severe TBI were enrolled. 10 patients were examined as controls. In patients, the monocyte population as well as the granulocyte population was significantly increased within 72 hours after TBI. The BBB's integrity did not have a significant influence on the cell count in the CSF.

Necrotizing fasciitis in a young patient with acute myeloid leukemia - a diagnostic challenge.

BACKGROUND: Necrotizing fasciitis is characterized by a fulminant destruction of the soft tissue with an alarmingly high mortality rate. One of the main reasons for the continued high mortality is due to the challenge to punctual recognize and diagnose this disease, as specific cutaneous signs can vary or even be missing early in its evolution - especially in case of simultaneous first manifestation of an acute leukemia. CASE PRESENTATION: An untypical case of necrotizing fasciitis disease in a young patient with the first diagnosis of acute myeloid leukemia is presented. After her induction chemotherapy the only presenting clinical sign was fever in the presence of severe neutropenia without an evident infectious focus. After a few days a painless confluent, erythematous, pustular skin rash with a central necrosis on lateral thigh appeared. Escherichia coli was isolated from blood cultures. Surgical debridement was performed and showed subcutaneous tissue, fascia and underlying muscle around the site of initial cutaneous manifestation with typical necrosis on exploration. But, initially taken skin biopsy did not show any typical histopathological findings like bacteria or inflammatory cells confirming necrotizing fasciitis. Nevertheless, the intraoperative findings were impressive and highly indicative for a necrotizing soft tissue infection, so that the patient was treated according to clinical guidelines with extensive recurrent surgical debridement, broad-spectrum antibiotics and intensive care therapy. After recovering from NF, she successfully underwent further chemotherapy and stem cell transplantation. CONCLUSION: The presented case highlights the risk of potential misinterpretation, delayed diagnosis and treatment of necrotizing fasciitis in patients presenting with an untypical clinical and histopathological manifestation of necrotizing fasciitis as a result of severe neutropenia following chemotherapy for acute myeloid leukemia.

Increased activation of the transcription factor c-Jun by MAP kinases in monocytes of multiple trauma patients is associated with adverse outcome and mass transfusion.

BACKGROUND: Post-traumatic dysfunction of the immune system is a major source of morbidity and mortality in patients with multiple trauma. The underlying intracellular mechanisms are still incompletely understood. Previous mRNA expression studies in monocytes suggested an involvement of the MAP kinases p38 and JNK and of the transcription factor c-Jun. Therefore, it was the aim of this study to elucidate whether alterations in the protein expression p38 MAPK, JNK, and c-Jun could be linked to PRBC substitution and survival. MATERIALS AND METHODS: Thirty-seven patients with blunt multiple injuries and an ISS > 16 points were enrolled in our study. Blood was drawn on admission and 6, 12, 24, 48, and 72 h after the traumatic event. Monocytes were isolated immediately after sample collection and nuclear protein was extracted and phosphoprotein concentrations were measured. The resulting data were statistically analyzed. RESULTS: An increased activation of MAP kinases and c-Jun could be shown in patients who died from their injuries. Additionally, patients who received PRBC substitution ≥10 units exhibited increased expression of activated MAP kinases and c-Jun. CONCLUSIONS: We present a serial, sequential investigation in human monocytes of major trauma patients evaluating the activation of p38 MAPK, JNK and c-Jun in the post-traumatic period. We show that death after trauma and massive PRBC substitution are associated with activation of this pathway. The p38 MAPK, JNK, and c-Jun have well established proinflammatory properties. Therefore, it appears likely that this pathway is involved in the systemic hyperinflammatory states seen after massive PRBC transfusion and multiple trauma.

The Munich Shoulder Questionnaire (MSQ): development and validation of an effective patient-reported tool for outcome measurement and patient safety in shoulder surgery.

BACKGROUND: Outcome measurement in shoulder surgery is essential to evaluate the patient safety and treatment efficiency. Currently this is jeopardized by the fact that most patient-reported self-assessment instruments are not comparable. Hence, the aim was to develop a reliable self-assessment questionnaire which allows an easy follow-up of patients. The questionnaire also allows the calculation of 3 well established scoring systems, i.e. the Shoulder Pain and Disability Index (SPADI), the Constant-Murley Score (CMS), and the Disabilities of the Arm, Shoulder and Hand (DASH) Score. The subjective and objective items of these three systems were condensed into a single 30-questions form and validated against the original questionnaires. METHODS: A representative collective of patients of our shoulder clinic was asked to fill in the newly designed self-assessment Munich Shoulder Questionnaire (MSQ). At the same time, the established questionnaires for self-assessment of CONSTANT, SPADI and DASH scores were handed out. The obtained results were compared by linear regression analysis. RESULTS: Fifty one patients completed all questionnaires. The correlation coefficients of the results were r = 0.91 for the SPADI, r = -0.93 for the DASH and r = 0.94 for the CMS scoring system, respectively. CONCLUSIONS: We developed an instrument which allows a quantitative self-assessment of shoulder function. It provides compatible data sets for the three most popular shoulder function scoring systems by one single, short 30-item. This instrument can be used by shoulder surgeons to effectively monitor the outcome, safety and quality of their treatment and also compare the results to published data in the literature.

Comparison of intraosseous versus central venous vascular access in adults under resuscitation in the emergency department with inaccessible peripheral veins.

INTRODUCTION: Current European Resuscitation Council (ERC) guidelines recommend intraosseous (IO) vascular access, if intravenous (IV) access is not readily available. Because central venous catheterisation (CVC) is an established alternative for in-hospital resuscitation, we compared IO access versus landmark-based CVC in adults with difficult peripheral veins. METHODS: In this prospective observational study we investigated success rates on first attempt and procedure times of IO access versus central venous catheterisation (CVC) in adults (≥ 18 years of age) with inaccessible peripheral veins under trauma or medical resuscitation in a level I trauma centre emergency department. RESULTS: Forty consecutive adults under resuscitation were analysed, each receiving IO access and CVC simultaneously. Success rates on first attempt were significantly higher for IO cannulation than CVC (85% versus 60%, p=0.024) and procedure times were significantly lower for IO access compared to CVC (2.0 versus 8.0 min, p<0.001). As for complications, failure of IO access was observed in 6 patients, while 2 or more attempts of CVC were necessary in 16 patients. No other relevant complications like infection, bleeding or pneumothorax were observed. CONCLUSIONS: IO vascular access is a reliable bridging method to gain vascular access for in-hospital adult patients under resuscitation with difficult peripheral veins. Moreover, IO access is more efficacious with a higher success rate on first attempt and a lower procedure time compared to landmark-based CVC.

Pathway analysis in microarray data: a comparison of two different pathway analysis devices in the same data set.

Oligonucleotide microarray technology has been developed to a very powerful and favorable biotechnique. However, it is an explicit challenge to judge the potential biological meaning of such extensive amounts of data. There are various-commercially available or free-software applications for pathway analyses on microarray data on the market. The aim of the present study was to test whether pathway analyses on the same data set using different commercially available devices lead to roughly comparable or massively diverging results and, if so, to give potential explanations. Two different commercially available pathway analysis programs (GeneGo and Pathway Studio 6) have been elected. The programs have been compared concerning their different analyses tools, underlying databases, database constructions, and network-building algorithms. The same data set has been uploaded into two different programs. Pathway analysis was performed according to the following three criteria: the five top networks, the five top diseases, and the five top canonical networks that are associated with the uploaded gene list. The different programs differ in extracting their information from the literature, in database construction, and network-building algorithms. The "top networks," as suggested by the programs as to be "most important," substantially differ from each other and share only one same gene. Concerning the most represented diseases in the data set, there are certain overlaps but no uniform results in the different applications. Pathway analyses of microarray data using preformed software devices offer valuable options for investigating on the biological relevance and function of a focus gene set. However, there is no standard in constructing such programs. This leads to substantial differences when investigating on the same data set using different devices. The intention of this work is to sensitize for the potentialities and also pitfalls doing pathway analysis using automated software tools.

Comparison of two intraosseous access devices in adult patients under resuscitation in the emergency department: A prospective, randomized study.

INTRODUCTION: Current guidelines recommend intraosseous (IO) vascular access in adults if peripheral venous access is unavailable. Most available data derive from children, animal models, cadaver studies or the prehospital setting. Therefore we compared two different IO access devices in adults under resuscitation in the hospital setting. PATIENTS AND METHODS: This prospective, randomized clinical study compared two different IO access devices in adults (>/=18 years of age) under trauma or medical resuscitation admitted to our emergency department with impossible peripheral venous access. Each adult was randomized to either spring-loaded BIG Bone Injection Gun or battery-powered EZ-IO. Outcome measures included success rates on first attempt, procedure times and complications. RESULTS: Forty consecutive adults under resuscitation were enrolled. Twenty patients received the BIG, another twenty patients the EZ-IO. Over all success rate on first attempt was 85% and mean procedure time 2.0min+/-0.9. Comparing the two devices, success rate on first attempt was 80% for the BIG versus 90% for the EZ-IO and mean procedure time was 2.2min+/-1.0 for the BIG versus 1.8min+/-0.9 for the EZ-IO. The differences between both IO devices were not statistically significant. No other relevant complications like infection, extravasation or bleeding were observed. CONCLUSIONS: IO vascular access was a reliable and safe method to gain rapid vascular access for in-hospital adult emergency patients under resuscitation. Further studies are necessary regarding comparative effectiveness of different IO devices.

Is the intraosseous access route fast and efficacious compared to conventional central venous catheterization in adult patients under resuscitation in the emergency department? A prospective observational pilot study.

BACKGROUND: For patients' safety reasons, current American Heart Association and European Resuscitation Council guidelines recommend intraosseous (IO) vascular access as an alternative in cases of emergency, if prompt venous catheterization is impossible. The purpose of this study was to compare the IO access as a bridging procedure versus central venous catheterization (CVC) for in-hospital adult emergency patients under resuscitation with impossible peripheral intravenous (IV) access. We hypothesised, that CVC is faster and more efficacious compared to IO access. METHODS: A prospective observational study comparing success rates and procedure times of IO access (EZ-IO, Vidacare Corporation) versus CVC in adult (>/=18 years of age) patients under trauma and medical resuscitation admitted to our emergency department with impossible peripheral IV catheterization was conducted. Procedure time was defined from preparation and insertion of vascular access type until first drug or infusion solution administration. Success rate on first attempt and procedure time for each access route was evaluated and statistically tested. RESULTS: Ten consecutive adult patients under resuscitation, each receiving IO access and CVC, were analyzed. IO access was performed with 10 tibial or humeral insertions, CVC in 10 internal jugular or subclavian veins. The success rate on first attempt was 90% for IO insertion versus 60% for CVC. Mean procedure time was significantly lower for IO cannulation (2.3 min +/- 0.8) compared to CVC (9.9 min +/- 3.7) (p < 0.001). As for complications, failure of IO access was observed in one patient, while two or more attempts of CVC were necessary in four patients. No other relevant complications, like infection, bleeding or pneumothorax were observed. CONCLUSION: Preliminary data demonstrate that IO access is a reliable bridging method to gain vascular access for in-hospital adult emergency patients under trauma or medical resuscitation with impossible peripheral IV access. Furthermore, IO cannulation requires significantly less time to enable administration of drugs or infusion solutions compared to CVC. Because CVC was slower and less efficacious, IO access may improve the safety of adult patients under resuscitation in the emergency department.

Hemorrhage and subsequent allogenic red blood cell transfusion are associated with characteristic monocyte messenger RNA expression patterns in patients after multiple injury-a genome wide view.

INTRODUCTION: As outcome to severe trauma is frequently affected by massive blood loss and consecutive hemorrhagic shock, replacement of red blood cell (RBC) units remains indispensable. Administration of RBC units is an independent risk factor for adverse outcome in patients with trauma. The impact of massive blood transfusion or uncrossmatched blood transfusion on the patients' immune response in the early posttraumatic period remains unclear. MATERIAL: Thirteen patients presenting with blunt multiple injuries (Injury Severity Score >16) were studied. Monocytes were obtained on admission and at 6, 12, 24, 48, and 72 hours after trauma. Biotinylated complementary RNA targets were hybridized to Affymetrix HG U 133A microarrays. The data were analyzed by a supervised analysis based on whether the patients received massive blood transfusions, and then subsequently, by hierarchical clustering, and by Ingenuity pathway analysis. RESULTS: Supervised analysis identified 224 probe sets to be differentially expressed (p < 0.001) in patients who received massive blood transfusion, when compared with those who did not. In addition, 331 probe sets were found differentially expressed (p < 0.001) in patients who received uncrossmatched RBC units in comparison with those who exclusively gained crossmatched ones. Functional pathway analysis of the respectively identified gene expression profiles suggests a contributory role by the AKT/PI3Kinase pathway, the mitogen-activated protein-kinase pathway, the Ubiquitin pathway, and the diverse inflammatory networks. CONCLUSION: We exhibited for the first time a serial, sequential screening analysis of monocyte messenger RNA expression patterns in patients with multiple trauma indicating a strongly significant association between the patients' genomic response in blood monocytes and massive or uncrossmatched RBC substitution.

Analysis of N-terminal pro-B-type natriuretic peptide and cardiac index in multiple injured patients: a prospective cohort study.

INTRODUCTION: Increased serum B-type natriuretic peptide (BNP) has been identified for diagnosis and prognosis of impaired cardiac function in patients suffering from congestive heart failure, ischemic heart disease, and sepsis. However, the prognostic value of BNP in multiple injured patients developing multiple organ dysfunction syndrome (MODS) remains undetermined. Therefore, the aims of this study were to assess N-terminal pro-BNP (NT-proBNP) in multiple injured patients and to correlate the results with invasively assessed cardiac output and clinical signs of MODS. METHODS: Twenty-six multiple injured patients presenting a New Injury Severity Score of greater than 16 points were included. The MODS score was calculated on admission as well as 24, 48, and 72 hours after injury. Patients were subdivided into groups: group A showed minor signs of organ dysfunction (MODS score less than or equal to 4 points) and group B suffered from major organ dysfunction (MODS score of greater than 4 points). Venous blood (5 mL) was collected after admission and 6, 12, 24, 48, and 72 hours after injury. NT-proBNP was determined using the Elecsys proBNP(R) assay. The hemodynamic monitoring of cardiac index (CI) was performed using transpulmonary thermodilution. RESULTS: Serum NT-proBNP levels were elevated in all 26 patients. At admission, the serum NT-proBNP values were 116 +/- 21 pg/mL in group A versus 209 +/- 93 pg/mL in group B. NT-proBNP was significantly lower at all subsequent time points in group A in comparison with group B (P < 0.001). In contrast, the CI in group A was significantly higher than in group B at all time points (P < 0.001). Concerning MODS score and CI at 24, 48, and 72 hours after injury, an inverse correlation was found (r = -0.664, P < 0.001). Furthermore, a correlation was found comparing MODS score and serum NT-proBNP levels (r = 0.75, P < 0.0001). CONCLUSIONS: Serum NT-proBNP levels significantly correlate with clinical signs of MODS 24 hours after multiple injury. Furthermore, a distinct correlation of serum NT-proBNP and decreased CI was found. The data of this pilot study may indicate a potential value of NT-proBNP in the diagnosis of post-traumatic cardiac impairment. However, further studies are needed to elucidate this issue.

Intrathecal and systemic concentration of NT-proBNP in patients with severe traumatic brain injury.

Outcome of patients suffering from traumatic brain injury (TBI) depends on the development of secondary brain damage. In this context, recent studies underlined the role of the natriuretic peptides- atrial natriuretic peptide and brain natriuretic peptide (BNP)-in aneurysmatic subarachnoidal hemorrhage (SAH). Especially BNP correlates with intracranial pressure and clinical outcome after SAH. Since its role in TBI remains unclear, the intracranial and systemic concentrations of N-terminal (NT)-proBNP were analyzed in patients suffering from severe TBI. We measured NT-proBNP levels in cerebrospinal fluid (CSF) and serum of 14 patients suffering from severe TBI (GCS15 mm Hg (n=6), the serum (800+/-150 pg/mL) and CSF levels (55+/-9 pg/mL) of NT-proBNP were significantly increased after 24 h, as compared to patients with ICP15 mm Hg. Further studies are currently performed to elucidate the physiologic role of NT-proBNP in TBI.

An enzyme-linked immunosorbent assay for human cathepsin X, a potential new inflammatory marker.

The human lysosomal cysteine-type carboxypeptidase cathepsin X is mainly present in monocytes and macrophages and may be released into the circulation due to constitutive and/or regulated secretion by (activated) immune cells. To define its potential diagnostic value as an inflammatory marker, we have developed a highly sensitive and specific sandwich-type immunoassay (ELISA) for cathepsin X permitting both intra- and extracellular detection and quantification. The dynamic range of the cathepsin X ELISA was determined to be 100 (detection limit) to 8000 pg/ml. Reproducibility of both within and between runs yielded coefficients of variation (CVs) of 2.7-3.5% and 6.3-7.3%, respectively. Cross-reactivity with other members (cathepsin B, L) of the thiol-dependent cathepsin family was not observed. The ELISA was used to quantify cathepsin X in leukocytes as well as in plasma of healthy volunteers and patients with multiple trauma. During the first 72 h after trauma, plasma levels of cathepsin X increased significantly, particularly in patients who died during the posttraumatic period. In comparison to the well-known inflammation marker neutrophil elastase, cathepsin X levels predicted survival with a higher significance in the later posttraumatic phase. In conclusion, this report provides the first evidence of cathepsin X immunoreactivity not only in cell lysates but also in plasma samples. We suggest that the newly developed highly reproducible ELISA will be of great value for further evaluation of this protease as a diagnostic and/or prognostic marker in inflammatory diseases.

Genome-wide monocytic mRNA expression in polytrauma patients for identification of clinical outcome.

Immune activation in multiple trauma is closely linked to the development of multiple organ dysfunction and failure, and consequently, has a profound influence on patient outcome. Although peripheral blood monocytes play a critical role in this immune response, the biological significance of changes in genome-wide expression immediately after traumatic injury have not been explored previously. Thirteen patients presenting with multiple blunt trauma were studied. Peripheral blood monocytes were obtained within 90 min and at 6, 12, 24, 48, and 72 h after trauma. Apparent genome-wide expression was determined with Affymetrix U133A microarrays. Supervised analysis identified 698 probe sets that were differentially expressed in the 13 trauma subjects (P < 0.001) over the 72-h study period. An additional 763 probe sets were differentially expressed in patients who died (n = 3) compared with those who survived (n = 10). The ability of these probe sets to function as a classifier of survival was significantly demonstrated with six prediction models. Using pathway analysis, a network of proinflammatory genes and intracellular signaling pathways leading to c-JUN activation were consistently overexpressed in patients who died. Genome-wide mRNA expression patterns in circulating peripheral blood monocytes from multiple-injured patients can discriminate clinical outcome. The pattern of gene expression in patients who died suggests that in these individuals, there is a reprioritization of gene expression consistent with an early activation of selected genes involved in the initiation and propagation of a proinflammatory response.