Rheological analyses of coagulation of blood from different individuals with special reference to procoagulant activity of erythrocytes.

In our previous papers, we reported that factor IX (FIX), when activated by erythrocyte membranes, causes coagulation. We have identified and characterized the FIX-activating enzyme located in normal human erythrocyte membranes. In this paper, to examine physiological and pathological significances of procoagulant activity of erythrocytes, coagulation of blood obtained from different individuals was analyzed by means of a rheological technique. In more than 65% of subjects including normals and patients, the initiation of coagulation seemed to be governed by erythrocytes. Coagulation of whole blood and platelet-free plasma supplemented with erythrocytes had a tendency to occur rapidly in the elderly. It was suggested that the concentration of FIX-activating enzyme on erythrocyte membranes for aged donors was somewhat higher than that for young ages. Propagation reactions on erythrocyte membranes (i.e. factor X activation leading to thrombin generation after FIX activation) was slower than that on platelet membranes. Moreover, the propagation reaction on erythrocyte membranes was greatly dependent on individuals, whereas that on platelet membranes was not so much. Our study demonstrates that the activation of FIX by erythrocytes and subsequent propagation reaction on platelet membranes may be important for initiating and controlling blood coagulation reactions.     

Neural Mechanism of Propofol Anesthesia in Severe Depression: A Positron Emission Tomographic Study

Background: The precise neural mechanisms of propofol anesthesia in humans are still unknown. The authors examined the acute effects of propofol on regional cerebral blood flow (rCBF) using positron emission tomography in patients with severe depression.

Methods: In six severely depressed patients (mean age, 55.0 yr) scheduled for electroconvulsive therapy, anesthetic levels were monitored by electroencephalography, and rCBF was serially quantified in the awake, sedated, and anesthetized states. The authors used high-resolution positron emission tomography with 15O-labeled water and statistical parametric mapping 99 for imaging and analysis of the data.

Results: Global cerebral blood flow showed sharp decreases from the awake level during the administration of propofol, decreasing 26.8% in the sedated state and 54.4% in the anesthetized state. Moreover, a dose effect was seen in both parietal cortices and the left lateral prefrontal region with larger regions of relative decrease in rCBF at higher propofol doses. At the higher dose, the values of rCBF in the pulvinar nucleus of the thalamus, the pontine tegmentum, and the cerebellar cortex were also affected. Meanwhile, there were few changes of relative rCBF in the basal frontal lobes during both sedated and anesthetized states.     

Objective examination for two-point stimulation using a somatosensory oddball paradigm: an MEG study.

OBJECTIVE: To establish an objective two-point discrimination test using magnetoencephalography (MEG). METHODS: First, we determined the discrimination threshold (DT) of the two-points. In the first experiment, we applied 0.9DT as standard stimuli, and 0.8DT, 1.1DT and 2DT as deviant stimuli in Conditions 1, 2 and 3, respectively. In the second experiment, we used 2DT and 0.9DT as the standard and deviant stimuli, respectively, in Condition 1. We applied two-stimuli that subjects felt as definitely one point or two-points in Condition 2 and 3, respectively. RESULTS: In the first experiment, the components peaking around 30-70 and 150-250ms following deviant stimuli were significantly larger than those following standard stimuli. Considering the peak latency, these components seem consistent with the magnetic mismatch field (MMF). In the second experiment, the MMF was recorded only in Condition 1. Therefore, it is considered that the MMF was recorded only when subjects automatically discriminate one point from two-points stimuli. CONCLUSIONS: This novel method can be used in neurophysiological two-point discrimination tests without the need to rely on the examiners' skills and subjects' reactions. SIGNIFICANCE: We confirmed that our new method could be used for the objective examination of two-point spatial discrimination.     

Transient Abnormal Myelopoiesis in Down's Syndrome

Recent data have elucidated the pathogenesis of transient abnormal myelopoiesis (TAM) to a great extent. TAM is a monoclonal disorder which resolves spontaneously and the target cell in this disorder is a multipotent stem cell which is capable of differentiating into megakaryocytes. The pathogeneses of TAM/AMKL (acute megakaryoblastic leukemia) appears to be closely associated with abnormal quality and quantity of a gene located on chromosome 21. AMKL developing after the regression of TAM appears to come from the same clone as the TAM, which apparently experiences some kind of genetic alterations. It seems that the gene responsible for TAM will soon be cloned in the near future. However, the mechanism of spontaneous regression of TAM has as yet not been clarified. The expanding clone in the transient phsysiological immunodeficient state, during the perinatal period, might be eliminated with the maturation of more mature immunosurveilance. Alternatively, the TAM clone might be destined to undergo spontaneous death, which is called “programmed cell death” (apoptosis). The mechanism of this phenomenon awaits further elucidation.     

Evaluation by statistical brain perfusion SPECT analysis on MRI findings, kana pick-out test and Mini-Mental State Examination results in patients with forgetfulness]

The aim of this single photon emission computed tomography(SPECT) study was to determine the abnormality of the regional cerebral blood flow(rCBF) using a three-dimensional stereotactic surface projection (3 D-SSP) in 18 patients who were referred to the hospital because of forgetfulness. Two intergroup comparison by 3 D-SSP analysis was conducted based on MRI, kana pick-out test and Mini-Mental State Examination (MMSE) results. Of the MRI findings, in the brain atrophy group, rCBF was decreased in the posterior cingulate gyrus, medial temporal structure and parieto-temporal association cortex; these rCBF-decreased areas are similar to the Alzheimer disease pattern. In the group where the MMSE was normal but the kana pick-out test was abnormal, rCBF was decreased in the posterior cingulate gyrus and cinguloparietal transitional area. In the group where both the MMSE and kana pick-out test were abnormal, rCBF was decreased in the parieto-temporal association cortex, temporal cortex and medial temporal structure. These results suggest that 3 D-SSP analysis of the SPECT with MMSE and the kana pick-out test provides the possibility of early diagnosis of initial stage of Alzheimer's disease.     

Acceleration of surgical angiogenesis in necrotic bone with a single injection of fibroblast growth factor-2 (FGF-2).

The aim of this study was to accelerate angiogenesis in necrotic bone by combining vascular bundle implantation and fibroblast growth factor-2 (FGF-2) administration. Twenty-four Japanese white rabbits were evaluated in this study. A portion of a rabbit iliac crest bone was removed as a free bone graft and frozen in liquid nitrogen to ensure complete cellular necrosis. A narrow hole was created in the bone and the graft was placed in the proximal thigh. In group 1, FGF-2 was injected into the hole at a single dose of 100 microg, and the saphenous artery and its venae comitantes were passed through the hole of the bone. In group 2, injection of saline into the hole and the vascular bundle implantation was used as a control. Neovascularization around the vessel was evaluated at weeks 1 and 2 after surgery. Neovascularization was observed along the implanted vascular bundle in both groups. At both 1 and 2 weeks after surgery, the vessel density of group 1 was significantly higher than that of group 2. The average length of newly formed vessels of group 1 was also significantly longer than that of group 2 at both 1 and 2 weeks after surgery. Both the vessel density and length were greater in week 2 animals than week 1. A local single injection of FGF-2 improved surgical angiogenesis in necrotic bone in this study. As FGF-2 is recognized as a potent mitogen for a variety of mesenchymal cells, the combination of vascular bundle implantation and FGF-2 administration may contribute to the treatment of ischemic osteonecrosis.     

Predictive factors for vascularized iliac bone graft for nontraumatic osteonecrosis of the femoral head

We reviewed the results of 35 operations performed on 29 patients with osteonecrosis of the femoral head in which a pedicle iliac bone was utilized. The average age was 35 years (17–62). There were 28 patients of stage 2 and 7 of stage 3; there were 17 type C-1 hips and 18 type C-2 hips. The pedicle bone was inserted in the anterolateral direction of the femoral head. The average follow-up period was 8 years and 7 months. Collapse of the femoral head occurred in 19 hip joints. Although 16 of 28 stage 2 hips showed collapse, all 7 stage 3 hips resulted in collapse. Thirteen of 17 hips did not show collapse in patients with type C-1 necrosis, whereas 15 of 18 hips developed collapse in patients with type C-2 necrosis. When the bone graft was inserted in the anterolateral direction of the femoral head, incidence of collapse was reduced. These results indicate that deep circumflex iliac pedicle bone graft may be indicated for stage 2 type C-1 necrosis, and that the penetration of the graft into the anterolateral aspect of the lesion is essential for the procedure to succeed.