Update on Intensive Neuromonitoring for Patients with Traumatic Brain Injury: A Review of the Literature and the Current Situation

Intracranial pressure (ICP) measurements are fundamental in the present protocols for intensive care of patients during the acute stage of severe traumatic brain injury. However, the latest report of a large scale randomized clinical trial indicated no association of ICP monitoring with any significant improvement in neurological outcome in severely head injured patients. Aggressive treatment of patients with therapeutic hypothermia during the acute stage of traumatic brain injury also failed to show any significant beneficial effects on clinical outcome. This lack of significant results in clinical trials has limited the therapeutic strategies available for treatment of severe traumatic brain injury. However, combined application of different types of neuromonitoring, including ICP measurement, may have potential benefits for understanding the pathophysiology of damaged brains. The combination of monitoring techniques is expected to increase the precision of the data and aid in prevention of secondary brain damage, as well as assist in determining appropriate time periods for therapeutic interventions. In this study, we have characterized the techniques used to monitor patients during the acute severe traumatic brain injury stage, in order to establish the beneficial effects on outcome observed in clinical studies conducted in the past and to follow up any valuable clues that point to additional strategies for aggressive management of these patients.     

Recent Advances and Future Directions of Hypothermia Therapy for Traumatic Brain Injury

For severe traumatic brain injury (TBI) patients, no effective treatment method replacing hypothermia therapy has emerged, and hypothermia therapy still plays the major role. To increase its efficacy, first, early introduction is important. Since there are diverse pathologies of severe TBI, it is necessary to appropriately control the temperature in the hypothermia maintenance and rewarming phases by monitoring relative to the pathology. Currently, hypothermia is considered appropriate for severe TBI patients requiring craniotomy for removal of hematoma, while induced normothermia is appropriate for severe TBI patients with diffuse brain injury. Induced normothermia is expected to exhibit a cerebroprotective effect equivalent to hypothermia, as well as reduce the complexity of whole-body management and systemic complications. According to the Japan Neurotrauma Data Bank of the Japan Society of Neurotraumatology, the brain temperature was controlled in 43.9% of severe TBI patients (induced normothermia: 32.2%, hypothermia: 11.7%) in Japan. Brain temperature management was performed mainly in young patients, and the outcome on discharge was favorable in patients who received brain temperature management. Particularly, patients who need craniotomy for removal of hematoma were a good indication of therapeutic hypothermia. Improvement of therapeutic outcomes with widespread temperature management in TBI patients is expected.     

Heterogeneity of hepatitis B virus genotype D in Japan

OBJECTIVE: Hepatitis B virus (HBV) genotypes B and C are predominant in Japan. Previously, we reported that approximately 9% of HBV carriers in the Ehime area of western Japan were infected with genotype D (HBV/D) and their sequences closely related. Recently, serum samples from 3 patients with chronic HBV/D infections living in Tokyo and the surrounding area became available for testing. The purpose of this study was to determine whether the HBV/D isolates from these different areas of Japan are closely related. METHODS: Of the 3 Tokyo area patients infected with HBV/D, 2 had chronic hepatitis, and 1 had hemophilia with a history of frequent coagulation factor injections. The complete HBV/D genome sequences of each were determined, and compared with those of subjects from the Ehime area. RESULTS: All 3 HBV/D sequences had a genomic length of 3,182 bases, and the hepatitis B surface antigen subtype was ayw3. Phylogenetic analysis revealed that the 1 of the HBV/D isolates was closely related to the isolates from Ehime Prefecture, while 1 was similar and 1 was clearly distinct. CONCLUSION: Our results indicate that HBV/D infections in Japan are heterogeneous.     

Sphingosylphosphorylcholine is a novel messenger for Rho-kinase-mediated Ca2+ sensitization in the bovine cerebral artery: unimportant role for protein kinase C

Although recent investigations have suggested that a Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle contraction plays a critical role in the pathogenesis of cerebral and coronary vasospasm, the upstream of this signal transduction has not been elucidated. In addition, the involvement of protein kinase C (PKC) may also be related to cerebral vasospasm. We recently reported that sphingosylphosphorylcholine (SPC), a sphingolipid, induces Rho-kinase-mediated Ca2+ sensitization in pig coronary arteries. The purpose of this present study was to examine the possible mediation of SPC in Ca2+ sensitization of the bovine middle cerebral artery (MCA) and the relation to signal transduction pathways mediated by Rho-kinase and PKC. In intact MCA, SPC induced a concentration-dependent (EC50=3.0 micromol/L) contraction, without [Ca2+]i elevation. In membrane-permeabilized MCA, SPC induced Ca2+ sensitization even in the absence of added GTP, which is required for activation of G-proteins coupled to membrane receptors. The SPC-induced Ca2+ sensitization was blocked by a Rho-kinase inhibitor (Y-27632) and a dominant-negative Rho-kinase, but not by a pseudosubstrate peptide for conventional PKC, which abolished the Ca2+-independent contraction induced by phorbol ester. In contrast, phorbol ester-induced Ca2+ sensitization was resistant to a Rho-kinase inhibitor and a dominant-negative Rho-kinase. In primary cultured vascular smooth muscle cells, SPC induced the translocation of cytosolic Rho-kinase to the cell membrane. We propose that SPC is a novel messenger for Rho-kinase-mediated Ca2+ sensitization of cerebral arterial smooth muscle and, therefore, may play a pivotal role in the pathogenesis of abnormal contraction of the cerebral artery such as vasospasm. The SPC/Rho-kinase pathway functions independently of the PKC pathway.     

Thrombolysis with rt-PA under Rivaroxaban Anticoagulation in a Hypertensive Rat Model of Intraluminal Middle Cerebral Artery Occlusion

Background

The aim of this study was to assess the risk and the threshold of hemorrhagic transformation (HT) after treatment with recombinant tissue plasminogen activator (rtPA) under the novel oral anticoagulant, rivaroxaban.

DISSEMINATED INTRAVASGULAR COAGULATION (DIC)

Renal tissues of 208 autopsied cases were examined. Malignant neoplasm with hematological malignancies often accompanied DIG. Tissue sections were stained with hematoxylin and eosin and Mallory's phosphotungstic acid hematoxylin (PTAH), and were applied for immunoperoxidase method (IP), using antisera against human fibrinogen, FDP-D and FDP-E. Histologically in 80 cases (38%) fibrin or fibrinogen related materials (FRMs) were observed in the glomerular capillary or the intratubular area or in both. FRMs were PTAH or IP positive or both in 23 of the 26 cases (88%) clinically diagnosed as DIC. In the remaining three cases anticoagulants probably Interfered with FRMs observation. This study showed the PTAH stain was nonspecific and insensitive to FRMs, and that IP was necessary for a pathological diagnosis of DIC. The presence of FRMs in the renal tubuli is an important finding in confirming DIG. DIC may be present histologically in the absence of clinical DIC symptoms.     

CHARACTERISTICS OF HISTIOCYTIC LESIONS IN THE RETICULOENDOTHELIAL SYSTEM OF NZB MICE

The so-called Potter's lesion, previously described as preneoplastic in the lymph nodes of C58 mice, develops frequently in autoimmune NZB mice. These lesions were characterized in the present study by bands or sheets of palestaining histiocytic cells in the cortex and medulla of the lymph node, and multiple small nodules of the same cells were found in the red pulp of the spleen and the liver. Electron microscopically, the cells had pleomorphic cytoplasm with long processes, electron-dense bodies, abundant mitochondria, and a characteristic labyrinth structure with many C-type viruses. Mac-1 antigen, IgG-Fc receptor, ferritin, and ACPase activity were identified on these cells. Intraperitoneally-injected iron colloids were found in the lesions of the spleen and liver but not in those of the lymph nodes. The lymph node lesions appeared when the mice were about 3 months of age and enlarged until the mice were around 10 months old, after which they gradually receded and were replaced by small vessels and fibroblastic cells. These data indicate that the lesions represent reactive hyperplasia of the macrophage system and may have no direct association with the development of malignant lymphoma in NZB mice.