Cognitive impairment after traumatic brain injury: a functional magnetic resonance imaging study using the Stroop task

The anterior cingulate cortex (ACC) plays a key role in cognition, motor function, and emotion processing. However, little is known about how traumatic brain injury (TBI) affects the ACC system. Our purpose was to compare, by functional magnetic resonance imaging (fMRI) studies, the patterns of cortical activation in patients with cognitive impairment after TBI and those of normal subjects. Cortical activation maps of 11 right-handed healthy control subjects and five TBI patients with cognitive impairment were recorded in response to a Stroop task during a block-designed fMRI experiment. Statistical parametric mapping (SPM99) was used for individual subjects and group analysis. In TBI patients and controls, cortical activation, found in similar regions of the frontal, occipital, and parietal lobes, resembled patterns of activation documented in previous neuroimaging studies of the Stroop task in healthy controls. However, the TBI patients showed a relative decrease in ACC activity compared with the controls. Cognitive impairment in TBI patients seems to be associated with alterations in functional cerebral activity, especially less activation of the ACC. These changes are probably the result of destruction of neural networks after diffuse axonal injury and may reflect cortical disinhibition attributable to disconnection or compensation for an inefficient cognitive process.     

Changes in femoral vein blood flow velocity by intermittent pneumatic compression: calf compression device versus plantar-calf sequential compression device

Intermittent pneumatic compression has become widely used to prevent deep venous thrombosis potentially causing fatal pulmonary embolism. Although uniform compression has been commonly applied, a new method of sequential compression from plantar to calf has recently been developed. In this report, changes in maximum blood flow velocity in the femoral vein were compared with compression of only the calf uniformly and compression from plantar to calf sequentially in 10 healthy adult volunteers. A compression pressure of 60mmHg was applied for 5min, and the velocity was measured before and after this treatment by ultrasound echography. There was no statistically significant difference in the change in maximum velocity between calf compression and plantar-calf sequential compression. The maximum velocity increased significantly with both compressions. However, plantar-calf sequential compression tended to have a greater effect. Although the results did not demonstrate an advantage of plantar-calf sequential compression compared with calf compression only, if the former compression is applied for a long time, it may have a greater effect.     

Role of Dok-1 and Dok-2 in myeloid homeostasis and suppression of leukemia

Dok-1 and Dok-2 are closely related rasGAP-associated docking proteins expressed preferentially in hematopoietic cells. Although they are phosphorylated upon activation of many protein tyrosine kinases (PTKs), including those coupled with cytokine receptors and oncogenic PTKs like Bcr-Abl, their physiological roles are largely unidentified. Here, we generated mice lacking Dok-1 and/or Dok-2, which included the double-deficient mice succumbed to myeloproliferative disease resembling human chronic myelogenous leukemia (CML) and chronic myelomonocytic leukemia. The double-deficient mice displayed medullary and extramedullary hyperplasia of granulocyte/macrophage progenitors with leukemic potential, and their myeloid cells showed hyperproliferation and hypo-apoptosis upon treatment and deprivation of cytokines, respectively. Consistently, the mutant myeloid cells showed enhanced Erk and Akt activation upon cytokine stimulation. Moreover, loss of Dok-1 and/or Dok-2 induced blastic transformation of chronic phase CML-like disease in mice carrying the bcr-abl gene, a cause of CML. These findings demonstrate that Dok-1 and Dok-2 are key negative regulators of cytokine responses and are essential for myeloid homeostasis and suppression of leukemia.     

Mechanism of carcinogenesis in familial tumors

It is thought that malignant tumors occur through interactions of multiple environmental factors and a personal genetic factor. A normal somatic cell having an intrinsic function is able to acquire the characteristics of a malignant cell under the influence of many factors. A small percentage of all tumors have obvious familial aggregation. These entities are called familial cancer. The familial cancer syndrome is well defined for colorectal cancer, breast cancer, endocrine neoplasia, and so on. Traits of familial tumors are sequentially inherited by offspring through gametes in a Mendelian fashion, most commonly in an autosomal-dominant manner. Carcinogenesis requires multiple genetic events. A patient with a familial tumor is ahead of an individual without any germline mutation in the carcinogenesis process. In such a situation, patients frequently suffer from multiple malignant tumors at a young age. It is well known that three major genes are closely related to the cell cycle and tumorigenesis. These gene types are protooncogenes, tumor suppressor genes, and DNA mismatch repair genes. Proto-oncogenes function to accelerate cells during the G₁ or growth phase of the cell cycle. Tumor suppressor genes act as blocks against cell growth and proliferation. Inactivation of tumor suppressor genes requires alterations in both alleles. These phenomena are known as Knudsons two-hits theory. However, DNA mismatch repair genes are known as caretaker genes and correct mismatch pair generation during DNA replication. Germline mutation of DNA mismatch repair genes causes hereditary nonpolyposis colorectal cancer. The tumor phenotype from patients with hereditary nonpolyposis colorectal cancer is demonstrated to be microsatellite instability positive.     

Spinal anesthesia hypotension in elective cesarean section in parturients wearing extra-strong compression stockings

We have routinely applied an extra-strong graduated compression stocking to cesarean section patients to reduce the incidence of spinal anesthesia hypotension. Because bupivacaine has recently become available in Japan, we compared the incidence of spinal hypotension using either 2.0 ml of hyperbaric 0.3% dibucaine or 0.5% bupivacaine. There were 98 full-term parturients wearing the stocking who received 2.0 ml injection of dibucaine or bupivacaine for elective cesarean section. When systolic blood pressure decreased to 90–100 mm Hg or to less than 70% of the pre-anesthesia value, ephedrine was injected intravenously. There was no significant difference in systolic blood pressure or heart rate during spinal anesthesia between the dibucaine and bupivacaine groups. Although the demographic data and various data related to anesthesia or surgery were similar in the groups, the fluid volume and the dose and incidence of ephedrine injection during anesthesia showed significant differences: the mean dose was 3.6 and 1.5 mg and the incidence was 41% and 19% in the dibucaine and bupivacaine groups, respectively. Spinal anesthesia using bupivacaine results in a lower incidence of spinal hypotension compared with dibucaine and, in combination with fitting the extra-strong stockings onto both legs, is clinically useful for cesarean sections. Received: 14 November 2001 / Accepted: 3 December 2001 Correspondence to H. Iwama     

Arrangement of artificial teeth in the neutral zone after surgical reconstruction of the mandible: a clinical report

This clinical report describes the fabrication of a fixed partial denture, supported and retained by implants, for a patient with unfavorable tongue movement caused by movable grafted skin on the floor of the mouth after surgical reconstruction of the mandible. The neutral zone technique was used, and successful results were obtained.     

Emergency craniotomy for intraparenchymal massive hematoma after embolization of supratentorial arteriovenous malformations

OBJECTIVE: We sought to evaluate the efficacy of emergency craniotomy for patients with massive hematoma secondary to endovascular embolization of supratentorial arteriovenous malformations (AVMs) and to investigate relevant factors affecting outcome. METHODS: Within the past 15 years, 605 patients with intracranial AVMs have undergone 1066 endovascular embolizations at our institution. Of these, 24 patients experienced intracranial hemorrhage during or after the procedure. Fourteen patients were demonstrated to have massive intraparenchymal hematomas and deteriorated to a comatose state (Glasgow Come Scale score < or =6). Twelve patients underwent craniotomy within 170 minutes of being diagnosed with intraparenchymal hemorrhage. The surgical procedures performed were hematoma evacuation with total (6 patients) or partial (2 patients) resection of the AVM or hematoma evacuation only (4 patients). The clinical records of these 12 patients were analyzed retrospectively. RESULTS: Nine patients recovered to a favorable condition (good recovery, four patients; moderately disabled, five patients), one patient remained in a persistent vegetative state, and two patients died. The interval between hemorrhage and emergency craniotomy was significantly shorter in patients with favorable outcomes than in those with poor clinical outcomes. Advanced age and a larger volume of intraoperative blood loss were the factors relevant to poor outcome. Temporal lobe location of the AVM and incomplete embolization tended to correlate to poor clinical outcome, but this correlation was not statistically significant. The sizes of the AVM and the hematoma did not correlate to patient outcome. There was no difference in outcomes with regard to the surgical procedure performed. CONCLUSION: In patients with massive postembolization hematomas, emergency craniotomy should be performed as soon as possible to achieve a favorable outcome. Cooperation among interventional neuroradiologists, intensive care physicians, and neurosurgeons is essential to manage AVM patients with critical postembolization hemorrhage. There is no need to persist in performing simultaneous total resection of the AVM at the emergency craniotomy.     

Abstracts presented at the Spring Conference 2003 of the Cancer Genetics Group, 12–13 May 2003, Southampton, UK

Abstract List

Abstracts presented at the Spring Conference 2003 of the Cancer Genetics Group, 12–13 May 2003, Southampton, UK     

Synergy of histone-derived peptides of coho salmon with lysozyme and flounder pleurocidin

Recent research has identified endogenous cationic antimicrobial peptides as important factors in the innate immunity of many organisms, including fish. It is known that antimicrobial activity, as well as lysozyme activity, can be induced in coho salmon (Oncorhynchus kisutch) mucus after exposure of the fish to infectious agents. Since lysozyme alone does not have antimicrobial activity against Vibrio anguillarum and Aeromonas salmonicida, a four-step protein purification protocol was used to isolate and identify antibacterial fractions from bacterially challenged coho salmon mucus and blood. The purification consisted of extraction with hot acetic acid, extraction and concentration on a C(18) cartridge, gel filtration, and reverse-phase chromatography on a C(18) column. N-terminal amino acid sequence analyses revealed that both the blood and the mucus antimicrobial fractions demonstrated identity with the N terminus of trout H1 histone. Mass spectroscopic analysis indicated the presence of the entire histone, as well as fragments thereof, including a 26-amino-acid N-terminal segment. These fractions inhibited the growth of antibiotic-supersuscptible Salmonella enterica serovar Typhimurium, as well as A. salmonicida and V. anguillarum. Synthetic peptides identical to the N-terminally acetylated or C-terminally amidated 26-amino-acid fragment were inactive in antimicrobial assays, but they potentiated the antimicrobial activities of the flounder peptide pleurocidin, lysozyme, and crude lysozyme-containing extracts from coho salmon. The peptides bound specifically to anionic lipid monolayers. However, synergy with pleurocidin did not appear to occur at the cell membrane level. The synergistic activities of inducible histone peptides indicate that they play an important role in the first line of salmon defenses against infectious pathogens and that while some histone fragments may have direct antimicrobial effects, others improve existing defenses.