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Biomedical subjects

S Nakao

Publications and source records attributed to S Nakao.

At least 163 records · Page 9Linked to original sources

Increase in the delta ST/delta heart rate (HR) index: a new predictor of restenosis after successful percutaneous transluminal coronary angioplasty.

With the goal of improving the prediction of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we evaluated the usefulness of the delta ST/delta heart rate (HR) index derived from serial exercise treadmill tests. Exercise treadmill tests were performed by 125 patients with single-vessel coronary artery disease before and several days after PTCA, and just before follow-up angiography 3 to 12 months later. Simple HR-adjusted indexes of ST-segment depression during exercise (delta ST/delta HR index) were derived. We compared the usefulness of the increase in delta ST/delta HR index at follow-up over the value obtained several days after PTCA for prediction of restenosis with that of a positive exercise treadmill test and a positive thallium scintigram at follow-up. At follow-up, 47 of the 125 patients showed restenosis. The delta ST/delta HR index increased in 43 of 47 patients in the restenosis group and in 18 of 78 patients without restenosis (p < 0.0001). Separate analysis of each criterion revealed the following respective values for sensitivity, specificity, and positive and negative predictive values for prediction of restenosis; increased delta ST/delta HR index of follow-up: 91%, 77%, 70%, and 94%; positive exercise treadmill test: 83%, 65%, 59%, and 86%; and positive thallium scintigram: 79%, 78%, 69%, and 86%. The increased delta ST/delta HR index had a significantly (p < 0.05) higher sensitivity than the positive thallium scintigram and a significantly (p < 0.01) higher specificity than the positive exercise treadmill test. An increased delta ST/delta HR index at follow-up identifies subgroups of patients who are at high risk for restenosis after PTCA.

Aged↗

Right ventricular stiffness measured by a new method without volume estimation in coronary artery disease.

This study was designed to measure the right ventricular (RV) stiffness (delta P/ delta V) with a new method without estimating the RV volume itself. RV stiffness has rarely been measured due to the difficulty in estimating the RV volume. Without measuring RV volume itself, stiffness can be determined by measuring its volume change (delta V). Tricuspid filling flow volume, which is the diastolic RV delta V, is measurable by using Doppler echocardiography. Thus, RV stiffness may possibly be obtained from Doppler echocardiography combined with high-fidelity RV pressure. Subjects consisted of 8 controls, 8 patients with angina pectoris, 8 with anterior, 8 with posterior, and 8 with inferior prior myocardial infarction. Tricuspid annular dimension was measured by 2-dimensional echocardiography and the tricuspid annular area was calculated. Velocity-time integral of the tricuspid filling flow during the late diastole was measured by pulsed Doppler echocardiography. Then, the late diastolic RV delta V was obtained as the product of the tricuspid annular area and the integral. The late diastolic RV pressure rise (delta P) was also measured with a micromanometer catheter. The RV elastic chamber stiffness constant ([delta P/ delta V]/P) was obtained by dividing simple stiffness by the mean RV pressure during late diastole. The RV elastic chamber stiffness constant did not significantly differ among controls, patients with angina pectoris, and those with anterior and posterior myocardial infarction (0.0054 +/- 0.0009 vs 0.0057 +/- 0.0018 vs 0.0064 +/- 0.002 vs 0.0052 +/- 0.0019 ml-1). However, it was significantly increased in patients with inferior myocardial infarction (0.010 +/- 0.004 ml-1, p < 0.01 or 0.05) compared with those in the other 4 groups. These results suggest (1) that RV stiffness can be measured with a new method without RV volume estimation, and (2) that this new method is useful in evaluating RV diastolic pathophysiology in patients with coronary artery disease.

Aged↗

Nitrous oxide depresses somatocardiac sympathetic A- and C-reflexes in anesthetized rats.

Effect of nitrous oxide (N2O) on the somatosympathetic A- and C-reflexes was investigated using artificially ventilated rats anesthetized with alpha-chloralose and urethane. Somatocardiac sympathetic A- and C-reflexes were elicited in the inferior cardiac nerve by electrical stimulation of A and C afferent fibers of the tibial nerve, respectively. Both reflexes were depressed by inhalation of N2O for 20 min. The depression was greater in the C-reflex than in the A-reflex. The depressive effects of N2O on both reflexes were unchanged after pretreatment with intravenous naloxone (0.2 or 2.0 mg/kg) or by prolongation of the inhalation of N2O for 2 h. These results suggest that the opioid receptor is not involved and that acute tolerance is not developed in the depressive action of N2O on the somatosympathetic A- and C-reflexes.

Anesthetics, Inhalation↗

Polyclonal B cell chronic lymphoproliferative disease with hairy cell morphology: a case report and clonal studies.

We describe a patient who has a chronic polyclonal B lymphocyte proliferation with a hairy-cell appearance. A 48-year-old Japanese woman with marked splenomegaly, systemic lymphadenopathy, and leukocytosis was referred to out hospital. Laboratory examination revealed marked polyclonal IgG hypergammaglobulinemia. Morphologic examination of the patient's peripheral blood, including May-Giemsa staining and scanning electron microscopy, showed a monotonous proliferation of hairy-appearing mature lymphocytes. An immunophenotypic study revealed an expansion of cells with mature B cell antigens positive for CD11c; however, light-chain restriction was not seen. The lack of both immuno-globulin heavy-chain and T cell receptor gene rearrangements by Southern blot analysis indicated the polyclonal nature of the proliferating B cells. This was confirmed further by a clonal analysis of the patient's lymphocytes using an X-chromosome-linked restriction fragment polymorphism within the X-linked phosphoglycerate kinase (PGK) gene. Since chronic B cell lymphoproliferation with a hairy cell appearance has not been described previously, this case might be extremely rare, and has important implication for the pathogenesis of mature B cell lymphoproliferative diseases, including hairy cell leukemia.

B-Lymphocytes↗

Transesophageal Doppler echocardiographic assessment of left coronary blood flow velocity in chronic aortic regurgitation.

Assessment of systolic and diastolic coronary blood flow velocities (FVs) in patients with aortic regurgitation (AR) has remained a clinical challenge. We recorded left anterior descending coronary blood FV in 21 patients with chronic AR an in 6 control subjects using transesophageal pulsed Doppler echocardiography. In 7 patients FV was measured 4.0 +/- 5.2 months after aortic valve replacement. Peak and mean FVs during systole and diastole and systolic/diastolic ratios of these FVs were determined. Left ventricular (LV) mass index was calculated by means of standard M-mode echocardiography. In patients with severe AR, peak and mean systolic FVs were significantly increased (34 +/- 8 cm/sec and 21 +/- 6 cm/sec, respectively) compared with FVs in the control group (15 +/- 4 and 12 +/- 3 cm/sec, respectively) and in patients with mild AR (17 +/- 3 cm/sec and 13 +/- 2 cm/sec, respectively). Peak and mean systolic FVs were also significantly increased in severe AR (54 +/- 13 cm/sec and 33 +/- 9 cm/sec, respectively) compared with FVs in the control (30 +/- 8 cm/sec and 21 +/- 5 cm/sec, respectively) and mild AR groups (30 +/- 5 cm/sec and 21 +/- 4 cm/sec, respectively). Peak systolic and diastolic FVs were correlated significantly with LV mass index (r = 0.72 and r = 0.73, respectively). Systolic and diastolic FVs and LV mass index were significantly decreased, normalized or both after aortic valve surgery. In conclusion, LV mass seems to have an effect on the significantly increased systolic and diastolic left coronary blood FV pattern in patients with chronic, severe AR. Increased systolic and diastolic FV appears to be normalized in the late period after surgery.

Adult↗

High serum concentration of lipoprotein(a) is a risk factor for restenosis after percutaneous transluminal coronary angioplasty in Japanese patients with single-vessel disease.

To determine the relation between the concentration of lipoprotein(a) [Lp(a)] and restenosis after percutaneous transluminal coronary angioplasty (PTCA) in Japan, we studied 80 consecutive patients with single-vessel disease who successfully underwent PTCA. All were evaluated by follow-up angiography a mean of 6.9 months after PTCA and were divided into the restenosis (30 patients) and the non-restenosis (50 patients) groups. The serum Lp(a) concentration of 29 +/- 17 mg/dl in the restenosis group was significantly higher than that of 17 +/- 14 mg/dl in the nonrestenosis group (p < 0.01). Multiple logistic regression analysis for risk factors revealed a significant correlation between restenosis and Lp(a) (p < 0.003). The serum Lp(a) concentration was positively correlated with the coronary artery percent stenosis at the time of follow-up angiography (r = 0.32, p < 0.01). High serum concentration of Lp(a) is therefore a risk factor for restenosis after PTCA in Japan.

Adult↗

Response to immunosuppressive therapy and an HLA-DRB1 allele in patients with aplastic anaemia: HLA-DRB1*1501 does not predict response to antithymocyte globulin.

HLA-DRB1*1501, a subtype of HLA-DR2, has been shown to be closely associated with a good response to cyclosporine (CyA) therapy in patients with aplastic anaemia (AA). To determine whether this DRB1 allele can also predict a response to antithymocyte globulin (ATG) therapy in AA patients, we analysed the results of HLA-DRB1 typing in 59 Japanese patients who received ATG within 2 years after diagnosis of AA and also in 52 patients treated with CyA. All patients were divided into three groups: those with DRB1*1501, those with DRB1*1502, and those without either of these two alleles (DR2-). The response rate to ATG in DRB1*1501+ patients (56%) was not significantly higher than that in DRB1*1502+ patients (47%) and in the other DR2- patients (54%). In contrast, the response rate to CyA therapy in DRB1*1501+ patients (92%) was significantly higher than that in the DRB1*1502+ (41%) and in DR2- patients (57%). Multivariate analysis revealed that possessing DRB1*1501 was an independent factor significantly predictive of a good response to CyA. These results indicate that although identifying the DRB1*1501 allele in AA patients prior to therapy is predictive of a good response to CyA therapy, it does not have a predictive value for ATG therapy.

Adolescent↗

Relative erythroid hyperplasia in the bone marrow at diagnosis of aplastic anaemia: a predictive marker for a favourable response to cyclosporine therapy.

Predicting the treatment response of aplastic anaemia (AA) is essential when considering cyclosporine (CyA) therapy among several treatment options, because it requires at least 2 months determine whether the therapy is beneficial to a patient with AA. To identify the characteristics of patients with AA who are likely to respond to CyA therapy we retrospectively reviewed the clinical records and bone marrow smears of patients treated with CyA. Among 30 patients who received the therapy for at least 3 months within 1 year after diagnosis of AA, and who had not been exposed to antilymphocyte or antithymocyte globulin, 16 (53%) responded with disease remission. CyA-responsive patients had a significantly higher ratio of erythroblasts to granulocytes (E/G ratio) in the bone marrow at the time of diagnosis as compared with patients refractory to therapy (P = 0.004). Multivariate analysis revealed that a high E/G ratio ( > 0.6) was significantly associated with a good response to CyA (P = 0.03): 15 (83%) of the 18 patients with an E/G ratio > 0.6 responded, but only one (8%) of the 12 with an E/G ratio > or = 0.6 did. Although the presence of subclinical paroxysmal nocturnal haemoglobinuria was suspected from the relative erythroblastosis observed in the bone marrow of these patients, flow cytometric analysis of neutrophils in the peripheral blood failed to reveal neutrophils deficient for glycosyl-phosphatidylinositol (GPI) anchored membrane proteins in all but one case. Identification of the presence of relative erythroid hyperplasia in he bone marrow when AA is diagnosed may help to predict a favourable response to CyA therapy, and therefore facilitate the selection of optimal therapy for AA.

Adolescent↗

Sevoflurane, enflurane and isoflurane have no persistent postanaesthetic effects on the central nervous system in cats.

Several reports have appeared on postanaesthetic convulsive disorders in humans after enflurane and isoflurane anaesthesia. However, it is controversial if enflurane induces epileptiform electroencephalogram (EEG), abnormal behaviour, or both, lasting for several days after anaesthesia in laboratory animals. We chronically implanted electrodes for EEG recording in the cortex, medial amygdala and dorsal hippocampus, and for reticular multi-unit activity (R-MUA) in the midbrain reticular formation in five cats. Two weeks later they were anaesthetized with 5.0% sevoflurane, 3.5% enflurane or 4.8% isoflurane for 3-4 h. EEG recordings, R-MUA and behaviour were observed for 1-3 h, during both wakefulness and sleep, every day for 5-7 days after anaesthesia. None of the cats showed abnormal behaviour, or EEG or R-MUA abnormalities after any of the anaesthetics, not only during wakefulness but during slow-wave and paradoxical phases of sleep. These results suggest that if seizures occur after anaesthesia, volatile anaesthesia itself may not be the cause.

Amygdala↗

Halothane and diazepam inhibit ketamine-induced c-fos expression in the rat cingulate cortex.

BACKGROUND: Ketamine, a noncompetitive N-methyl-D-aspartate antagonist, has psychotomimetic side effects. Recent studies have shown that noncompetitive N-methyl-D-aspartate antagonists cause morphologic damage to the cingulate and retrosplenial cortices and induce c-fos protein (c-Fos) in the same regions. Although benzodiazepines are effective in preventing these side effects, the neural basis of the drug interactions has not been established. METHODS: The effects of diazepam and halothane on c-Fos expression induced by ketamine were studied. Diazepam (1 and 5 mg/kg) or vehicle were administered subcutaneously, followed 7 min later by 100 mg/kg ketamine given intraperitoneally. Halothane (1.0 and 1.8%), was administered continuously from 10 min before ketamine administration until brain fixation. Two hours after ketamine injection, rats were perfused and their brains fixed and extracted. Brain sections were prepared in a cryostat and c-Fos expression was detected using immunohistochemical methods. RESULTS: Ketamine induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices, thalamus, and neocortex. Diazepam suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices in a dose-dependent manner, leaving the thalamus and neocortex less affected. Halothane suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices and the neocortex in a dose-dependent manner, leaving the thalamus relatively unaffected. CONCLUSION: Halothane and diazepam inhibited ketamine-induced c-Fos expression in the cingulate and retrosplenial cortices, leaving the thalamus relatively unaffected.

Anesthetics, Inhalation↗

Hypercoagulability and high lipoprotein(a) levels in patients with aplastic anemia receiving cyclosporine.

There is some clinical evidence that cyclosporine A (CyA) is associated with thrombotic complications of bone marrow and renal transplantation. We investigated plasma concentrations of lipoprotein(a) [Lp(a)], a potentially atherothrombotic lipoprotein, and hemostatic and vascular status in ten patients with aplastic anemia receiving CyA, eleven patients not taking it, and 38 age-matched healthy controls. Patients receiving CyA had significantly higher concentrations of plasma fibrinogen (P < 0.05), prothrombin fragment 1 + 2 (F1 + 2; P < 0.05), plasminogen activator inhibitor-1 (PAI-1; P < 0.05), and von Willebrand factor antigen (P < 0.05) than did patients not taking CyA. Plasma concentrations of Lp(a) were higher in CyA-treated patients than those not receiving it (P < 0.05) or healthy controls (P < 0.05). The difference in the Lp(a) concentration between controls and patients who did not receive CyA-treatment was not significant. Our results suggest that hypercoagulability is likely to occur during CyA therapy. Further, the presence of high concentrations of Lp(a) may accelerate the process of atherosclerosis and increase thrombotic events in patients receiving long-term CyA.

Adult↗

Hematopoietic clone with karyotypic abnormalities of host origin after bone marrow transplantation: two case reports.

A patient with non-Hodgkin's lymphoma in remission developed a myelodysplastic syndrome (MDS) 12 years after ABMT. This patient had undergone bone marrow harvesting prior to any chemoradiotherapy. He had received the autograft following conditioning with high-dose CY and TBI. Chromosomal analysis of BM cells revealed complicated abnormalities. Similar karyotypic abnormalities in host-derived BM cells were found in another patient with AML who had received allogeneic BM following conditioning with CY plus TBI 15 months previously. These findings suggest that MDS or clonal karyotypic abnormalities following ABMT may derive from endogenous hematopoietic stem cells that survive the BMT preparative regimen.

Adult↗

-Rejection of an allogeneic bone marrow graft following successful treatment of severe graft-versus-host disease (GVHD).

A 38-year-old female with acute myelogenous leukemia (M2) received an allogeneic bone marrow graft from an HLA-DR one locus-mismatched sister during the first remission. The conditioning regimen consisted of busulfan and cyclophosphamide. Acute graft-versus-host disease (GVHD) developed on day 11 after transplantation. Although the GVHD was successfully treated with methylprednisolone, peripheral blood neutrophils that had begun to increase disappeared in association with improvement of the GVHD and graft rejection was eventually diagnosed. The second bone marrow transplantation from the same donor ended up with engraftment failure. She died of sepsis due to Candida albicans following the development of Epstein-Barr virus-associated B-lymphoproliferative disorder. The clinical course of this patient indicates that successful therapy of severe GVHD with methylprednisolone may lead to marrow graft rejection.

Acute Disease↗

Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic progenitor cells: increase of early hematopoietic progenitor cells in TNF receptor p55-deficient mice in vivo and potent inhibition of progenitor cell proliferation by TNF alpha in vitro.

Murine bone marrow cells with lineage phenotypes (Lin)-Sca-1+c-kit+ and Lin-Sca-1-c-kit+ cells represent primitive hematopoietic stem cells (HSCs) and committed hematopoietic progenitor cells, respectively. The number of Lin-Sca-1+c-kit+ HSCs in bone marrow was significantly increased in tumor necrosis factor (TNF) receptor p55-deficient (TNF-R55-1-) mice compared with the TNF-R55+/+ wild-type mice without a marked change in bone marrow cellularity. In both the methylcellulose culture and a single-cell proliferation assay, mouse TNF alpha (mTNF alpha) inhibited in vitro the proliferation of wild-type mouse-derived Lin-Sca-1+c-kit+ cells in response to a combination of multiple growth factors. The same is true for that of Lin-Sca-1+c-kit+ cells stimulated with granulocyte colony-stimulating factor (G-CSF) plus stem cell factor (SCF). Moreover, mTNF alpha significantly arrested the entry into S-phase from G0/G1 phase of Lin-Sca-1+c-kit+ cells stimulated with multiple growth factors and Lin-Sca-1-c-kit+ cells stimulated with G-CSF plus SCF. In contrast, mTNF alpha failed to affect the growth and cell cycle progression of Lin-Sca-1+c-kit+ cells and Lin-Sca-1-c-kit+ cells that were obtained from TNF-R55-deficient mice. These data suggest that TNF may be an important physiologic regulator of hematopoiesis and that TNF-R55 may be essentially involved in TNF-mediated inhibition of the growth of both primitive stem and more committed progenitor cells.

Animals↗