Direct Measurement of the Cosmic-Ray Proton Spectrum from 50 GeV to 10 TeV with the Calorimetric Electron Telescope on the International Space Station.

In this paper, we present the analysis and results of a direct measurement of the cosmic-ray proton spectrum with the CALET instrument onboard the International Space Station, including the detailed assessment of systematic uncertainties. The observation period used in this analysis is from October 13, 2015 to August 31, 2018 (1054 days). We have achieved the very wide energy range necessary to carry out measurements of the spectrum from 50 GeV to 10 TeV covering, for the first time in space, with a single instrument the whole energy interval previously investigated in most cases in separate subranges by magnetic spectrometers (BESS-TeV, PAMELA, and AMS-02) and calorimetric instruments (ATIC, CREAM, and NUCLEON). The observed spectrum is consistent with AMS-02 but extends to nearly an order of magnitude higher energy, showing a very smooth transition of the power-law spectral index from -2.81±0.03 (50-500 GeV) neglecting solar modulation effects (or -2.87±0.06 including solar modulation effects in the lower energy region) to -2.56±0.04 (1-10 TeV), thereby confirming the existence of spectral hardening and providing evidence of a deviation from a single power law by more than 3σ.

Extended Measurement of the Cosmic-Ray Electron and Positron Spectrum from 11 GeV to 4.8 TeV with the Calorimetric Electron Telescope on the International Space Station.

Extended results on the cosmic-ray electron + positron spectrum from 11 GeV to 4.8 TeV are presented based on observations with the Calorimetric Electron Telescope (CALET) on the International Space Station utilizing the data up to November 2017. The analysis uses the full detector acceptance at high energies, approximately doubling the statistics compared to the previous result. CALET is an all-calorimetric instrument with a total thickness of 30 X_{0} at normal incidence and fine imaging capability, designed to achieve large proton rejection and excellent energy resolution well into the TeV energy region. The observed energy spectrum in the region below 1 TeV shows good agreement with Alpha Magnetic Spectrometer (AMS-02) data. In the energy region below ∼300 GeV, CALET's spectral index is found to be consistent with the AMS-02, Fermi Large Area Telescope (Fermi-LAT), and Dark Matter Particle Explorer (DAMPE), while from 300 to 600 GeV the spectrum is significantly softer than the spectra from the latter two experiments. The absolute flux of CALET is consistent with other experiments at around a few tens of GeV. However, it is lower than those of DAMPE and Fermi-LAT with the difference increasing up to several hundred GeV. The observed energy spectrum above ∼1 TeV suggests a flux suppression consistent within the errors with the results of DAMPE, while CALET does not observe any significant evidence for a narrow spectral feature in the energy region around 1.4 TeV. Our measured all-electron flux, including statistical errors and a detailed breakdown of the systematic errors, is tabulated in the Supplemental Material in order to allow more refined spectral analyses based on our data.

Energy Spectrum of Cosmic-Ray Electron and Positron from 10 GeV to 3 TeV Observed with the Calorimetric Electron Telescope on the International Space Station.

First results of a cosmic-ray electron and positron spectrum from 10 GeV to 3 TeV is presented based upon observations with the CALET instrument on the International Space Station starting in October, 2015. Nearly a half million electron and positron events are included in the analysis. CALET is an all-calorimetric instrument with total vertical thickness of 30 X_{0} and a fine imaging capability designed to achieve a large proton rejection and excellent energy resolution well into the TeV energy region. The observed energy spectrum over 30 GeV can be fit with a single power law with a spectral index of -3.152±0.016 (stat+syst). Possible structure observed above 100 GeV requires further investigation with increased statistics and refined data analysis.

Relationship between cytokine single nucleotide polymorphisms and sarcoidosis among Japanese subjects.

Several susceptibility genes for sarcoidosis have been identified, but their relationship to the clinical state and prognosis remains to be elucidated. The aim of this study was to elucidate the relationship between sarcoidosis and five single nucleotide polymorphisms (SNPs) of three cytokines expected to play an important role in the inflammatory response. A case-control study was performed with 208 unrelated patients who met the diagnostic criteria for sarcoidosis used in Japan since 2006, and 328 control subjects. Five SNPs were analyzed: interleukin (IL)-10-819T/C (rs1800871), IL-10-592A/C(rs1800872), IL-6-634C/G (rs1800796), tumor necrosis factor-alpha (TNF-alpha)-857C/T (rs1799724), and TNF-alpha -1031T/C (rs1799964). No significant differences in SNPs were observed between the total sarcoidosis and control groups. However, the prevalence of rs1800871 and rs1800872 polymorphisms differed significantly in the sarcoidosis with eye involvement group compared with the control group [rs1800871 TT (vs. TC + CC): OR = 1.67, P = 0.034; rs1800872 AA (vs. AC + CC): OR = 1.66, P = 0.036]. Analyzing the cardiac involvement group, the prevalence of the rs1799724 polymorphism was significantly different from that of the control group [rs1799724 TT (vs. CC + CT): OR = 6.01. P = 0.006]. We concluded that the rs1799724 C/T polymorphism may affect susceptibility to cardiac sarcoidosis, while the rs1800871 T/C and rs1800872A/C polymorphisms may affect susceptibility to sarcoidosis with eye involvement.

High glucose attenuates insulin-induced mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in vascular smooth muscle cells.

The mechanisms for the effect of hyperglycemia on insulin-induced mitogenesis were investigated using rat vascular smooth muscle cells (VSMC). VSMC were preincubated in serum-free medium with low (5 mM) glucose (LG condition) or high (25 mM) glucose (HG condition), and examined for DNA synthesis using bromodeoxyuridine (BrdUrd) incorporation. Mitogen-activated protein kinase (MAPK) activity and MAPK phosphatase (MKP-1) protein expression were detected by Western blot analysis. Phosphatidylinositol 3-kinase (PI-3K) activity was detected by thin layer chromatography. Insulin induced a dose-dependent increase in BrdUrd incorporation (123.3+/-2.6% over basal level with 1 microM insulin) in the LG group and this effect was significantly enhanced (161.6+/-10.4% over basal level) in the HG group. In the LG group, MAPK activity was transient with a peak activation (137.4+/-11.2% over basal level) after 10 min exposure to 100 nM insulin. In the HG group, the MAPK activity was significantly potentiated (two-fold compared to the LG group) and was sustained even after 60 min. Insulin also induced PI-3K activity and MKP-1 expression, both of which were blocked by the PI-3K inhibitor wortmannin. In the HG group, insulin-induced PI-3K and MKP-1 expression was almost abolished. In conclusion, high glucose enhances insulin-induced mitogenesis associated with the potentiation of insulin-stimulated MAPK activity in VSMC. These effects of glucose might in part be due to the attenuation of MKP-1 expression through the blockage of the insulin-PI-3K signal pathway.

Pioglitazone enhances cytokine-induced apoptosis in vascular smooth muscle cells and reduces intimal hyperplasia.

BACKGROUND: Cytokines induce apoptosis in vascular disease lesions through enhancement of inducible nitric oxide (NO) synthase (iNOS) activation. The thiazolidinediones, novel insulin-sensitizing agents, have been demonstrated to modulate cytokine-induced NO production. We have investigated the role of pioglitazone in the apoptosis of vascular smooth muscle cells (VSMCs) in vitro and developed intimal hyperplasia in vivo. METHODS AND RESULTS: Pioglitazone (0.1 to 10 micromol/L) significantly enhanced cytokine-induced expression of iNOS and NO production in a dose-dependent manner in rat VSMCs, but 15-deoxy-Delta(12,14)-prostaglandin J2 (up to 10 micromol/L), a native peroxisome proliferator-activated receptor-gamma ligand, showed no effect. Pioglitazone also significantly enhanced reduction of cell viability, as evidenced by the increase in the number of TUNEL-positive cells. All of these effects of pioglitazone were blocked by treatment with N-monomethyl-L-arginine, an NO synthesis inhibitor. In an in vivo study with a balloon-injured rat carotid artery, neointimal thickness had reached maximum levels at 2 weeks after injury. Then, rats were fed with or without pioglitazone (3 mg. kg(-1). d(-1)) for an additional week. The ratio of intima to media area of carotid artery was significantly decreased by 30%, and the ratio of apoptotic cells in neointima was significantly increased in pioglitazone-treated rats compared with vehicle-treated control rats. CONCLUSIONS: Pioglitazone enhanced apoptosis in an NO-dependent manner in cytokine-activated VSMCs and induced significant regression of intimal hyperplasia in balloon-injured rat carotid artery. It appears that pioglitazone is a potent apoptosis inducer in vascular lesions, providing a novel pharmacological strategy to prevent restenosis after vascular intervention.

Enhanced expression of heparin-binding EGF-like growth factor and its receptor in hypertrophied left ventricle of spontaneously hypertensive rats.

OBJECTIVES: Although heparin-binding epidermal growth factor-like growth factor (HB-EGF) is thought to produce hypertrophy in isolated cardiomyocytes via an autocrine mechanism, the pathophysiological role of HB-EGF, in myocardial hypertrophy in vivo, is not yet known. To investigate the involvement of HB-EGF in cardiac remodeling associated with hypertension in vivo, we assayed the expression of HB-EGF mRNA and protein in the left ventricle (LV) during the development of left ventricular hypertrophy in spontaneously hypertensive rats (SHR). METHODS: Prior to sacrifice and assay of HB-EGF and EGF-receptor (EGF-R) mRNA, morphologic and hemodynamic variables were measured in SHR and in age-matched Wistar Kyoto rats (WKY). At 5, 9 and 12 weeks of age, rats were killed, their hearts were removed, and the expression of HB-EGF and EGF-R mRNA and protein were measured. In addition, SHR and WKY were treated with enalapril, atenolol, or both for 4 weeks. RESULTS: In untreated SHR, double products (i.e. systolic blood pressure (sBP) multiplied by heart rate (HR), an index of mechanical load, peaked at 9 weeks. Expression of HB-EGF mRNA was also observed to peak in these animals at 9 weeks, while expression of EGF-R mRNA increased from 5 to 9 weeks, but remained constant thereafter. In untreated WKY, double products and EGF-R mRNA expression did not change over time, whereas the level of HB-EGF message increased gradually. Antibody to HB-EGF reacted primarily with myocyte membranes in SHR, whereas antibody to EGF-R reacted mainly with interstitial cells in these animals. The angiotensin-converting enzyme inhibitor, enalapril, markedly decreased sBP in SHR, whereas the beta 1-adrenoreceptor antagonist, atenolol, significantly decreased HR. While neither alone affected the expression of HB-EGF mRNA, their combination significantly reduced the expression of HB-EGF mRNA, as well as double products, in these rats, but had no effect on expression of EGF-R mRNA. CONCLUSIONS: The enhanced expression of HB-EGF mRNA and protein in LV of SHR suggest that this growth factor may play an important role during the early development of LV hypertrophy and cardiac fibrosis in SHR. The association between double products and HB-EGF expression suggest that the latter may be induced by increased mechanical load and may contribute, in turn, to cardiac remodeling.

Relationship between serum lipoprotein(a) level and thrombin generation to the circadian variation in onset of acute myocardial infarction.

A high incidence of acute myocardial infarction (AMI) has been reported between 06:00 and 12:00 h. This may be related to an abnormality in hemostasis. An association has been founded between the serum lipid level and coronary atherosclerosis, as well as the serum lipid level and a hemostatic abnormality. We investigated the association between the time of AMI, the level of serum lipid, and of hemostatic factor. Of the 42 subjects evaluated retrospectively, 20 had experienced an AMI between 06:00 and 12:00 h (group A), while 22 had developed an AMI during some other period (group B). All patients received emergency coronary angiography, which identified a total occlusion of coronary artery in the proximal portion of the left antecedent branch. The serum level of several lipid factors and of hemostatic factors were compared between the two groups. Characteristics of patients were similar in both groups. The serum levels of lipoprotein(a) (Lp(a)) and of thrombin-antithrombin III complex (TAT) were higher in group A than in group B, respectively. The level of other factors were similar in both groups. Group A showed a significant correlation between the level of Lp(a) and TAT, with a tendency (not statistically significant), toward a positive correlation between Lp(a) and PAI-1, and a negative correlation between Lp(a) and t-PA. In a subgroup that experienced AMI in the early morning, a higher level of Lp(a) was associated with an elevation of TAT, a marker for thrombin generation, and with the level of fibrinolytic factor. This suggests that Lp(a) is closely related to the increase in the early morning incidence of AMI via a change in the prothrombotic state.

Glucose modifies the cross-talk between insulin and the beta-adrenergic signalling system in vascular smooth muscle cells.

BACKGROUND: Abnormalities in the vascular function of insulin are observed in insulin resistance, and hyperglycaemia is one of the important factors inducing insulin resistance. OBJECTIVE: To investigate the role of glucose in the interaction of insulin and beta-adrenergic signalling systems in vascular smooth muscle cells (VSMC). METHODS: After cells were treated with D-glucose (525 mmol/l) and insulin (100 nmol/l), adenylyl cyclase activity was measured in the presence of isoproterenol, forskolin, and cholera toxin. Assays for insulin-induced activities of insulin receptor substrate (IRS)-1, phosphoinositide 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) were performed. RESULTS: In the presence of low glucose concentrations (5 mmol/l), insulin enhanced isoproterenol-, forskolin- and cholera toxin-stimulated adenylyl cyclase activities. This stimulatory effect was abolished by PI3-K inhibitors, wortmannin, or LY294002. In contrast, in the presence of high glucose concentrations (25 mmol/l), insulin attenuated isoproterenol-stimulated activity but not cholera toxin- or forskolin-stimulated activity. Insulin-stimulated activities of IRS-1 and PI3-K, but not MAPK activity, were also attenuated in the presence of high concentrations of glucose. The MAPK kinase inhibitor, PD98059, abolished the inhibitory effect of insulin on the beta-adrenergic signalling system. Troglitazone and pioglitazone prevented this inhibitory effect of insulin by restoring IRS-1 and PI3-K activities. CONCLUSIONS: In the presence of low glucose concentrations, insulin stimulates the beta-adrenergic signalling system through the IRS-1/PI3-K pathway. However, in the presence of high glucose concentrations, the effect of insulin is switched to an inhibitory one, through the MAPK pathway. Our finding suggests that high glucose concentrations modify the cross-talk between insulin and the beta-adrenergic signalling systems in VSMC.

Comparison of cardiac sympathetic nervous function with left ventricular function and perfusion in cardiomyopathies by (123)I-MIBG SPECT and (99m)Tc-tetrofosmin electrocardiographically gated SPECT.

UNLABELLED: The objective of this study was to clarify the relationship between cardiac sympathetic nervous function (CSNF) and left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-eight cases (32 males, 6 females; mean age, 56 +/- 15 y), consisting of 5 healthy control subjects, 15 patients with DCM, and 18 patients with HCM, were studied with (123)I-metaiodobenzylguanidine (MIBG) and (99m)Tc-tetrofosmin SPECT. CSNF was evaluated from cardiac uptake and washout of MIBG, whereas LV perfusion and function were evaluated from tetrofosmin uptake and wall thickening on electrocardiographically gated SPECT. As quantitative parameters of global cardiac MIBG uptake and washout, the heart-to-mediastinum ratio (H/M) and percentage washout were calculated from early and delayed planar images. As quantitative regional parameters, the regional uptake and percentage washout of MIBG were calculated from SPECT images dividing the left ventricle into 12 segments. In the tetrofosmin study, the H/M and LV ejection fraction were calculated as the parameters of global LV perfusion and function. As quantitative regional parameters, the regional uptake and wall thickening were also calculated for the 12 myocardial segments using the quantitative gated SPECT software. Multiple linear regression analysis was performed to investigate the correlations between the parameters from the 2 studies. RESULTS: In DCM and HCM, multiple linear regression analysis of the regional parameters showed significant correlations between LV function and CSNF (P < 0.0001) and between LV perfusion and CSNF (P < 0.0001). According to the partial correlation coefficients, washout and early uptake of MIBG were the most significant factors for predicting LV function and LV perfusion, respectively. CONCLUSION: In cardiomyopathies, CSNF was closely related to LV function. The quantitative parameters of MIBG washout could reflect cardiac functional impairment. Early MIBG uptake might be determined by myocardial perfusion in cardiomyopathies.

Effects of lisinopril and nitrendipine on urinary albumin excretion and renal function in patients with mild to moderate essential hypertension.

The present study was designed to evaluate the effects of an ACE inhibitor, lisinopril, and a calcium antagonist, nitrendipine, on urinary albumin excretion (UAE) and renal function in mild to moderate essential hypertensive patients with microalbuminuria. After the 4-week drug-free period, 17 patients were randomly divided into two groups. The first group (group 1: n=8) received lisinopril 10-20 mg daily for 8 weeks followed by nitrendipine 5-10 mg daily for another 8 weeks. The second group (group 2: n=9) received nitrendipine 5-10 mg daily for 8 weeks followed by lisinopril 10-20 mg daily for another 8 weeks. The mean blood pressure (MBP) significantly decreased in a similar manner in both groups. UAE significantly decreased after 8 weeks of treatment with lisinopril in group 1 and after 8 weeks of subsequent treatment with lisinopril in group 2. On the other hand, UAE was not altered by treatment with nitrendipine. The changes in UAE were significantly correlated with changes in MBP after 8 weeks of treatment with nitrendipine, but not after 8 weeks of treatment with lisinopril. No significant changes in creatinine clearance, urinary excretion of sodium or urinary N-acetyl-beta-D-glucosaminide were observed by any treatment in either group. These results suggest that lisinopril, not nitrendipine, reduces UAE in essential hypertensive patients with microalbuminuria independently of its effective antihypertensive properties.

Measurement of the directional distribution of incident particles in the Shuttle-Mir mission orbit.

The measurement of the directional distribution of incident particles was made by using the Real time Radiation Monitoring Device (RRMD)-III placed inside the Space Shuttle STS-84 cruised at an altitude of 400 km and an inclination angle of 51.6 degrees, which are the same as the cruising orbit of the International Space Station (ISS). The directional distributions of incident particles were evaluated over the observed linear energy transfer (LET) range (1-100 keV/micrometers). The pitch angle distribution is also obtained using the geomagnetic model of IGRF-95. The result is roughly in good agreement with the distribution obtained by the VF1-MIN anisotropy model calculation within the present experimental errors, if the shielding distribution is assumed to be uniform.

Successful treatment of a patient with nephrotic syndrome associated with chronic lymphocytic leukemia.

We report the case of a 62-year-old man with nephrotic syndrome associated with stage B chronic lymphocytic leukemia (CLL). Kappa Bence Jones proteinuria and the glomerular deposition of kappa-light chain were observed. Although treatment with cyclophosphamide and prednisolone tended to reduce the level of proteinuria, the administration of angiotensin-converting enzyme inhibitor, enalapril, resulted in complete remission of nephrotic syndrome.

Transient pulsus alternans induced by isosorbide dinitrate: echocardiographic and hemodynamic evidence of reduced venous return--a case report.

Transient pulsus alternans was induced by isosorbide dinitrate (ISDN) in a patient with postmyocarditis congestive heart failure under diuretic therapy. The severity and duration of pulsus alternans depended on the dose of ISDN. According to the echocardiographic and hemodynamic examinations, the superimposed preload reduction caused by ISDN combined with decreased blood volume owing to diuretic therapy most likely contributed to the development of pulsus alternans.

Measurement of LET distribution and dose equivalent on board the space shuttle STS-65.

Space radiation dosimetry measurements have been made on board the Space Shuttle STS-65 in the Second International Microgravity Laboratory (IML-2). In these measurements, three kinds of detectors were used; one is a newly developed active detector telescope called "Real-time Radiation Monitoring Device (RRMD)" utilizing silicon semi-conductor detectors and others are conventional detectors of thermoluminescence dosimeters (TLDs) and CR-39 plastic track detectors. Using the RRMD detector, the first attempt of real-time monitoring of space radiation has been achieved successfully for a continuous period of 251.3 h, giving the temporal variations of LET distribution, particle count rates, and rates of absorbed dose and dose equivalent. The RRMD results indicate that a clear enhancement of the number of trapped particles is seen at the South Atlantic Anomaly (SAA) without clear enhancement of dose equivalent, while some daily periodic enhancements of dose equivalent due to high LET particles are seen at the lower geomagnetic cutoff regions for galactic cosmic ray particles (GCRs). Therefore, the main contribution to dose equivalent is seen to be due to GCRs in this low altitude mission (300 km). Also, the dose equivalent rates obtained by TLDs and CR-39 ranged from 146.9 to 165.2 microSv/day and the average quality factors from 1.45 to 1.57 depending on the locations and directions of detectors inside the Space-lab at this highly protected orbit for space radiation with a small inclination (28.5 degrees) and a low altitude (300 km). The LET distributions obtained by two different detectors, RRMD and CR-39, are in good agreement in the region of 15-200 keV/mm and difference of these distributions in the regions of LET < 15 keV/mm and LET > 200 keV/mm can be explained by considering characteristics of CR-39 etched track formation especially for the low LET tracks.

Measurements of LET distribution and dose equivalent onboard the Space Shuttle IML-2 (STS-65) and S/MM#4 (STS-79).

Space radiation dosimetry measurements have been made onboard the Space Shuttle STS-65 in the Second International Microgravity Laboratory (IML-2: 28.5 degrees x 300 km: 14.68 days) and the STS-79 in the 4th Shuttle MIR mission (S/MM#4: 51.6 degrees x 300-400km: 10.2 days). In these measurements, three kinds of detectors were used; one is a newly developed active detector telescope called "Real-time Radiation Monitoring Device (RRMD-I for IML-2 and RRMD-II with improved triggering system for S/MM#4)" utilizing silicon semi-conductor detectors and the other detectors are conventional passive detectors of thermoluminescence dosimeters (TLDs) and CR-39 plastic track detectors. The main contribution to dose equivalent for particles with LET > 5.0 keV/micrometer (IML-2) and LET > 3.5 keV/micrometer (S/MM#4) is seen to be due to galactic cosmic rays (GCRs) and the contribution of the South Atlantic Anomaly (SAA) is less than 5% (IML-2: 28.5 degrees x 300 km) and 15% (S/MM#4: 51.6 degrees x 400 km) in the above RRMD LET detection conditions. For the whole LET range (> 0.2 kev/micrometer) obtained by TLDs and CR-39 in these two typical orbits (a small inclination x low altitude and a large inclination x high altitude), absorbed dose rates range from 94 to 114 microGy/day, dose equivalent rates from 186 to 207 microSv/day and average quality factors from 1.82 to 2.00 depending on the locations and directions of detectors inside the Spacelab at the highly protected IML-2 orbit (28.5 degrees x 300 km), and also, absorbed dose rates range from 290 to 367 microGy/day, dose equivalent rates from 582 to 651 microSv/day and average quality factors from 1.78 to 2.01 depending on the dosimeter packages around the RRMD-II "Detector Unit" at the S/MM#4 orbit (5l.6 degrees x 400km). In general, it is seen that absorbed doses depend on the orbit altitude (SAA trapped particles contribution dominant) and dose equivalents on the orbit inclination (GCR contribution dominant). The LET distributions obtained by two different types of active and passive detectors, RRMDs and CR-39, are in good agreement for LET of 15 - 200 kev/micrometer and difference of these distributions in the regions of LET < 15 kev/micrometer and LET > 200 kev/micrometer can be explained by considering characteristics of CR-39 etched track formation especially for the low LET tracks and chemical etching conditions.

[Systemic and regional myocardial distribution of 123I-BMIPP in normal subjects].

We estimated the systemic and left ventricular (LV) regional myocardial distribution of 123I-BMIPP (beta-methyl-p-iodophenyl-pentadecanoic-acid) in normal subjects (n = 13, mean age 43.9). In planar studies, the count ratios of heart, lung and liver to mediastinum were 2.63, 1.28 and 3.80 in the early images, and 2.23, 1.20 and 2.26 in the delayed images, respectively. The uptake in liver was almost identical with that in heart in the delayed images. In SPECT studies, the regional relative counts in anterior, septal, posterior and lateral LV walls were 100, 98, 96 and 108 (%) in the initial images, and 100, 98, 99 and 107 (%) in the delayed images, respectively. The regional relative uptake was significantly higher in the lateral wall than those in the other parts of LV walls in both images. The relative counts in the basal, mid- and apical portions were 100, 111 and 87 (%) in the initial images, and 100, 113, 92 (%) in the delayed images, respectively. These results suggest that the myocardial regional distribution of BMIPP is not always uniform even in normal subjects. Thus, it is necessary to interpret with caution in the light of these findings, especially for detect in a myocardial lesion in an early phase of cardiomyopathy or a mild myocardial ischemia.

[Clinical significance of 123I-MIBG myocardial scintigraphy in patients with hypertrophic cardiomyopathy].

We studied the abnormality of myocardial sympathetic nervous system in patients with hypertrophic cardiomyopathy using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in comparison with the parameters of other clinical examinations. In 50 patients with HCM, the heart to mediastinum 123I-MIBG uptake ratio (H/M) was significantly low and washout rate (WR) of 123I-MIBG was significantly high respectively compared with normal subjects (n = 8). H/M was negatively correlated with serum norepinephrine level, wall thickness of left ventricle, left ventricular mass index, left ventricular end diastolic pressure respectively, and WR was positively correlated with those parameters respectively. On the other hand, LF/HF calculated by spectral analysis in holter electrocardiogram was positively correlated with H/M, and negatively correlated with WR. In HCM, H/M in patients with subjective symptoms was significantly lower than that without subjective symptoms, and WR in patients with paroxysmal atrial fibrillation was significantly higher than that without paroxysmal atrial fibrillation. This study revealed that H/M and WR reflected the severity and the difference of disease type in HCM. In conclusion, 123I-MIBG contributes to evaluating more details in diagnosis and pathophysiology of HCM.

[A psychological burden on patients with clinical trials during anesthesia].

We investigated with questionnaires, psychological outline of 30 patients, who were requested to participate in clinical trials of anti-tachycardia drugs during anesthesia. Although 14 patients consented to the trial, the consent was not based on adequate understanding or volunteerism in 3 patients. Nine patients of the consented group were anxious about the possible use of the trial drug. Eight patients of the rejected group felt anxiety on surgery and anesthesia, which was the most common reason for rejection. Forty % of refused patients felt a guilty conscience or embarrassed. Although we tried to obtain patients' consent following governmental and institutional regulations and guidelines, not only the consented but also the refused patients suffer from psychological burden with the clinical trial. It is of concern that recruitment to the trial enhances anxiety of the patients as they already feel uneasiness, unrest, and insecurity facing anesthesia and surgery. To avoid entry of less informed or unwilling patients to the clinical trial, we must secure patients' veto, and recruitment should be performed by clinicians who are not involved in anesthesia practice.

[Management of hypertension in patients with coronary artery disease].

The management of hypertensive patients with coronary artery disease (CAD) should be started with lifestyle modification for reduction of coronary risk factors. As the principle of drug therapy, rapid decrease in blood pressure below the limits of coronary auto-regulation must be avoided. Clinical trials showed J-curved relationship between diastolic pressure and mortality was not found above 75 mmHg. The current desired goal of blood pressure in patients with CAD might be suggested as 125-140/85-75 mmHg. Pulse pressure should be recognized as a strong predictor for CAD as well as systolic and diastolic blood pressure, especially in elderly patients. The choice of drug therapy have to be based on efficiency in clinical trials, side effects, and also particular condition of each patient.