【目的】ハンセン病治療薬として使用されてきたクロファジミン（CFZ）は、2021年9月に肺非結核性抗酸菌（NTM）症に対して保険審査上認可されることとなった。CFZを使用する際には心電図を定期的にモニターすることが推奨されているが、本剤と薬剤性QTc延長症候群との関連については相反する報告があり一致した見解は得られていない。更にCFZは添付文章上では半減期が10日と記載されており、定常状態に到達するまで長い日数を要するが、本剤によるQTc間隔への影響を長期的にモニターした報告はない。そこで本研究ではCFZの定常状態の血中濃度とQTc間隔との関連性を調査した。【方法】複十字病院に入院又は外来治療中でインフォームドコンセントが得られた肺NTM症患者45例を対象とし、前向き観察研究を実施した（UMIN000041053）。評価項目はCFZによる有害事象とし、原因暴露の指標としてCFZの血清中濃度を使用した。採血は1人あたり２～５点をCFZのトラフ付近で行い、高速液体クロマトグラフィー質量分析装置にてCFZ濃度を測定した。CFZ濃度は非線形混合効果モデルを用いて解析し、CFZの定常状態の血中濃度個別予測値とQTc間隔のベースラインからの変化量を相関分析した。なお、本研究は複十字病院及び明治薬科大学より研究倫理承認を受けて実施した。【結果・考察】組み入れられた45例の患者のうち43例は50mg/day、2例は100mg/dayのCFZを含むレジメンで治療された。母集団薬物動態解析の結果CFZの半減期は36日と推定され、定常状態に到達するまで144日以上を要することが明らかとなった。CFZの血中濃度が定常状態に到達した後にQTc間隔が測定されていた患者は35例おり、QTc間隔のベースラインからの変化量と定常状態の血中CFZ濃度は有意に相関した（相関係数：0.34、P値：＜0.001）。また、本研究ではQTc間隔500mSec以上、又はベースラインからQTc間隔が60mSec以上延長した患者は4例認められたが、いずれもU波の影響が疑われCFZとの関連性は否定的であった。更に本研究コホートではTorsades de pointesを発症した患者はおらず、QTc間隔のベースラインからの増加量は平均±SDで16.5±21 mSecと臨床的に問題とならない程度であった。【結論】CFZの定常状態の血清中濃度はQTc間隔と正の相関関係を示したが、投与量50mg/dayのCFZによるQTc延長症候群、及びTorsades de pointesのリスクは低いと考えられた。
We report multi-wavelength monitoring observations of an M-dwarf flare star AD Leonis with Seimei Telescope (6150--7930 Å), SCAT (Spectroscopic Chuo-university Astronomical Telescope; 3700--7500 Å), ...NICER (Neutron Star Interior Composition Explorer; 0.2--12.0 keV), and collaborations of OISTER (Optical and Infrared Synergetic Telescopes for Education and Research) program. Twelve flares are detected in total which include ten H\(\alpha\), four X-ray, and four optical-continuum flares; one of them is a superflare with the total energy of \(\sim\) 2.0\(\times\)10\(^{33}\) erg. We found that (1) during the superflare, the H\(\alpha\) emission line full width at 1/8 maximum dramatically increases to 14 Å from 8 Å in the low-resolution spectra (R\(\sim\) 2000) accompanied with the large white-light flares, (2) some weak H\(\alpha\)/X-ray flares are not accompanied with white-light emissions, and (3) the non-flaring emissions show clear rotational modulations in X-ray and H\(\alpha\) intensity in the same phase. To understand these observational features, one-dimensional hydrodynamic flare simulations are performed by using the RADYN code. As a result of simulations, we found the simulated H\(\alpha\) line profiles with hard and high-energy non-thermal electron beams are consistent with that of the initial phase line profiles of the superflares, while those with more soft- and/or weak-energy beam are consistent with those in decay phases, indicating the changes in the energy fluxes injected to the lower atmosphere. Also, we found that the relation between optical continuum and H\(\alpha\) intensity is nonlinear, which can be one cause of the non-white-light flares. The flare energy budget exhibits diversity in the observations and models, and more observations of stellar flares are necessary for constraining the occurrence of various emission line phenomena in stellar flares.
A 67-year-old man, in whom a linear ulcer running from the duodenal bulb to the descending part had been noted 3 years previously, was admitted to our hospital because of abdominal pain and melena. ...Duodenoscopy revealed a bleeding giant longitudinal ulcer, which was more extensive than before. Tests for Helicobacter pylori (Hp) were negative. The ulcer was cured by endoscopic hemostasis and repeated blood transfusions. Attention must be paid to Hp-negative post-bulbar duodenal ulcers because of the frequent complications including hemorrhage.
The Laser Interferometer Gravitational-wave Observatory Scientific Collaboration and Virgo Collaboration (LVC) sent out 56 gravitational-wave (GW) notices during the third observing run (O3). ...Japanese collaboration for Gravitational wave ElectroMagnetic follow-up (J-GEM) performed optical and near-infrared observations to identify and observe an electromagnetic (EM) counterpart. We constructed web-based system which enabled us to obtain and share information of candidate host galaxies for the counterpart, and status of our observations. Candidate host galaxies were selected from the GLADE catalog with a weight based on the three-dimensional GW localization map provided by LVC. We conducted galaxy-targeted and wide-field blind surveys, real-time data analysis, and visual inspection of observed galaxies. We performed galaxy-targeted follow-ups to 23 GW events during O3, and the maximum probability covered by our observations reached to 9.8%. Among them, we successfully started observations for 10 GW events within 0.5 days after the detection. This result demonstrates that our follow-up observation has a potential to constrain EM radiation models for a merger of binary neutron stars at a distance of up to \(\sim\)100~Mpc with a probability area of \(\leq\) 500~deg\(^2\).
We present optical observations of type Ia supernova (SN) 2019ein, starting at 2 days after the estimated explosion date. The spectra and the light curves show that SN 2019ein belongs to the ...High-Velocity (HV) and Bload Line groups with relatively rapid decline in the light curves (Delta m15(B) = 1.36 +- 0.02 mag) and the short rise time (15.37 +- 0.55 days). The Si II 6355 velocity, associated with a photospheric component but not with a detached high-velocity feature, reached ~ 20,000 km s-1 at 12 days before the B-band maximum. The line velocity however decreased very rapidly and smoothly toward the maximum light, where it was ~ 13,000 km s-1 as relatively low among HV SNe. This indicates that the speed of the spectral evolution of HV SNe Ia is correlated not only to the velocity at the maximum light, but also to the light curve decline rate like the case for Normal-Velocity (NV) SNe Ia. Spectral synthesis modeling shows that the outermost layer at > 17,000 km s-1 is well described by the O-Ne-C burning layer extending to at least 25,000 km s-1, and there is no unburnt carbon below 30,000 km s-1; these properties are largely consistent with the delayed detonation scenario, and are shared with the prototypical HV SN 2002bo despite the large difference in Delta m15(B). This structure is strikingly different from that derived for the well-studied NV SN 2011fe. We suggest that the relation between the mass of 56Ni (or Delta m15) and the extent of the O-Ne-C burning layer provides an important constraint on the explosion mechanism(s) of HV and NV SNe.
Young solar-type stars are known to show frequent "superflares", which may severely influence the habitable worlds on young planets via intense radiations and coronal mass ejections. Here we report ...an optical spectroscopic and photometric observation of a long-duration superflare on the young solar-type star EK Draconis (50-120 Myr age) with the Seimei telescope and \(Transiting\) \(Exoplanet\) \(Survey\) \(Satellite\) (\(TESS\)). The flare energy 2.6\(\times\)10\(^{34}\) erg and white-light flare duration 2.2 hr are much larger than those of the largest solar flares, and this is the largest superflare on a solar-type star ever detected by optical spectroscopy. The H\(\alpha\) emission profile shows no significant line asymmetry, meaning no signature of a filament eruption, unlike the only previous detection of a superflare on this star (Namekata et al. 2021, \(Nat.Astron\)). Also, it did not show significant line broadening, indicating that the non-thermal heating at the flare footpoints are not essential or that the footpoints are behind the limb. The time evolution and duration of the H\(\alpha\) flare are surprisingly almost the same as those of the white-light flare, which is different from general M-dwarf (super-)flares and solar flares. This unexpected time evolution may suggest that different radiation mechanisms than general solar flares are predominant, as follows: (1) radiation from (off-limb) flare loops, and (2) re-radiation via radiative backwarming, in both of which the cooling timescales of flare loops could determine the timescales of H\(\alpha\) and white light.
Kamiseii-san (kampo) has been known to be effective for periodontal disease from ancient times . This study was performed to investigate the effect of kampo on the alveolar bone resorption associated ...with experimental periodontitis induced with Actinomyces viscosus ATCC 15987 in hamsters . The amount of the bone resorption in the experimental animals was about half that in the controls . Kamiseii-san did not display any effect on the growth of the bacteria either in vivo or in vitro. These findings suggest that this agent had an inhibitory effect on alveolar bone resorption without affecting tha bacteria, and supports the traditional story. While the mechanism of the inhibition still remains unclear, it seems that some indirect action of Kamiseii-san may on alveolar bone metabolism result in inhibition.
Using topographic maps, we studied the scalp field distribution of somatosensory evoked potentials (SEPs) in response to the stimulation of the tibial (TN), sural (SN) and lateral femoral cutaneous ...(LFCN) nerves in 24 normal volunteers. Cortical peaks, i.e., N35, P40, N50 and P60 were generally dominant in the contralateral hemisphere for the LFCN-SEP, whereas all peaks except N35 had dominance in the ipsilateral hemisphere for TN- and SN-SEPs. The findings imply that ipsilateral or contralateral peak dominance for the lower extremity SEP is determined by where the cortical leg representation occurs. As a result, mesial hemisphere representation results in peak dominance projected to the hemisphere ipsilateral to stimulation. Representations at the superior lip of the interhemispheric fissure or lateral convexity lead to midline or contralateral peak dominance. These findings also suggest that the paradoxically lateralized P40 is not the result of a positive field dipole shadow generated by the primary negative wave in the mesial hemisphere, but is the primary positive wave, analogous to P26 of the median nerve SEP. Accordingly, contralaterally dominant N35 is likely equivalent to the first cortical potential of N20 in the median nerve SEP. The difference in vector directions of potential fields between N35 and P40 may account for the opposite hemispheric dominance for these peaks in TN- and SN-SEPs.
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