著者
Kazuhiko Higashioka Hiroaki Niiro Kenji Yoshida Kensuke Oryoji Kazuo Kamada Shinichi Mizuki Eisuke Yokota
出版者
一般社団法人 日本内科学会
雑誌
Internal Medicine (ISSN:09182918)
巻号頁・発行日
vol.55, no.5, pp.467-471, 2016 (Released:2016-03-01)
参考文献数
32
被引用文献数
9

Objective Low-dose trimethoprim-sulfamethoxazole (TMP-SMX) is commonly used to prevent pneumocystis pneumonia in daily practice. Previous reports have shown a relationship between high- or standard-dose of TMP-SMX and hyperkalemia, however it remains unclear whether this is true for low-dose TMP-SMX. In this study we sought to determine the risk factors for hyperkalemia associated with low-dose TMP-SMX. Methods In this retrospective cohort study, 186 consecutive adult patients who received TMP-SMX as prophylaxis for pneumocystis pneumonia from January 2014 to January 2015 were evaluated. Data on the patients' age, gender, baseline estimated glomerular filtration rate (eGFR), baseline serum potassium, maximum serum potassium, duration reaching the maximal serum potassium level, dosage, and concomitant use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), β-blockers, non-steroidal anti-inflammatory drugs and potassium-sparing diuretics were retrospectively collected. Hyperkalemia was defined as a serum potassium level ≥5 mEq/L. Univariate and multivariate analyses were performed. Results The median age of the patients was 66 years and 51.1% were men. Hyperkalemia associated with low-dose TMP-SMX was observed in 32 patients (17.2%). The median duration to reach the maximal serum potassium level was 12 days. The multivariate logistic regression analysis identified renal insufficiency to be a major risk factor for hyperkalemia associated with low-dose TMP-SMX (eGFR <60 mL/min/1.73 m2, adjusted OR 4.62). Moreover, in the subpopulation of patients with renal insufficiency, ACEi/ARB use was considered to be a major risk factor for hyperkalemia (adjusted OR 3.96). Conclusion Renal insufficiency in concert with ACEi/ARB use is a major risk factor for hyperkalemia induced by low-dose TMP-SMX.
著者
Atsushi Watanabe Shigeki Yoneyama Mikio Nakajima Norihiro Sato Ryoko Takao-Kawabata Yukihiro Isogai Aki Sakurai-Tanikawa Kazuhiro Higuchi Akihito Shimoi Hideyuki Yamatoya Kenji Yoshida Terutomo Kohira
出版者
The Japanese Society of Toxicology
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.37, no.3, pp.617-629, 2012-06-01 (Released:2012-06-01)
参考文献数
14
被引用文献数
57 69

Teriparatide, a therapeutic agent for osteoporosis, has been reported to increase the incidences of bone neoplasms such as osteosarcoma when administered subcutaneously to Fischer 344 (F344) rats for a long term, but its non-carcinogenic dose level following 2-year daily administration has not been established. Here we report detailed studies on the carcinogenicity of teriparatide following long-term administration. When teriparatide was administered subcutaneously to male and female Sprague-Dawley (SD) rats daily for 2 years, the incidence of osteosarcoma was increased at 13.6 μg/kg/day. The non-carcinogenic dose level was 4.5 μg/kg/day for both males and females. The development of osteosarcoma in SD rats depends on the dose level of, and treatment duration with, teriparatide. Responses of the bones to teriparatide were similar between F344 and SD rats in many aspects. These results suggested that the carcinogenic potential of teriparatide in SD rats is essentially the same as in F344 rats.
著者
Yoshitaka Hirasawa Atsushi Fujiwara Kazuya Tabata Kenji Yoshida Tsutomu Negama Takayuki Anzai Shin-ichi Sato
出版者
The Japanese Society of Toxicology
雑誌
Fundamental Toxicological Sciences (ISSN:2189115X)
巻号頁・発行日
vol.7, no.2, pp.105-114, 2020 (Released:2020-03-27)
参考文献数
33

The purpose of this study was to profile cytokine storms (cytokine release syndrome) in the LPS-induced disseminated intravascular coagulation (DIC)-cynomolgus monkey model by measuring changes in 22 cytokines using Luminex. In this study, increases were noted in 20 cytokines, excluding IL-4 and IL-17A. Specifically, IL-6, IL-8, G-CSF and TNF-α, pro-inflammatory cytokines, and IL-10, an anti-inflammatory cytokine, as well as MCP-1, markedly increased by 10,000 pg/mL or more. In addition to the marked increases in the pro-inflammatory cytokines IL-6 and G-CSF, the concentrations of IL-5, IL-18, IFN-γ, VEGF and IL-15 increased continuously. Also, in addition to the marked increases in the pro-inflammatory cytokine IL-8 as well as in MCP-1, the concentrations of IL-1ra, IL-2, IL-1β, IL-12/23 (p40), GM-CSF and TGF-α gradually decreased after initially increasing. On the other hand, in addition to the marked increases in the pro-inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10, MIP-1β and MIP-1α transiently increased and then rapidly disappeared from serum. IL-13 increased at 6 hr after administration only. Since the behavior of cytokines in this monkey model was similar to those noted in DIC in humans, this model will be useful for evaluating the efficacy of anti-DIC drugs. In addition, this model will also be useful for assessing the risk of cytokine storm development, which is a serious adverse effect of certain types of antibody drugs and CAR-T cell-based therapies.
著者
Kenji YOSHIDA Hisanori ITOH
出版者
Meteorological Society of Japan
雑誌
気象集誌. 第2輯 (ISSN:00261165)
巻号頁・発行日
vol.90, no.3, pp.377-401, 2012-06-25 (Released:2012-06-30)
参考文献数
46
被引用文献数
12 17

This study examines the indirect effect of tropical cyclones (TCs) on cases of heavy rainfall during the Baiu season in Kyushu, Japan using data analyses and numerical experiments. A detailed analysis of the heavy rainfall event that occurred on 7 June 1999 (JST) is performed. This event was remotely affected by Typhoon Maggie (9903), which was located approximately 2000 km from Kyushu at the time. As Typhoon Maggie passed close to Taiwan, a high potential vorticity (PV) zone appeared to the north of Taiwan. A low PV region formed simultaneously to the east of Taiwan, corresponding to a northwestward extension of the Pacific high. These dynamical changes induced an enhanced southerly moisture flux between the high PV zone and the low PV region, leading to moisture convergence and heavy rain in the vicinity of Kyushu. During this time, Typhoon Maggie also caused the northward advection of a separate tropical disturbance.The high PV zone to the north of Taiwan was produced by diabatic heating associated with interplay between the circulation of Typhoon Maggie and the topography of Taiwan. In contrast, the low PV region was formed through the advection of low-PV air from low latitudes by Typhoon Maggie. A piecewise PV inversion diagnostic shows that the low PV region was the largest contributor to the southerly moisture flux, although both Typhoon Maggie and the high PV zone also made positive contributions. Numerical experiments reveal that the precipitation in and around Kyushu was enhanced by both the topography of Taiwan and the northward advection of the additional tropical disturbance.This study identifies a new mechanism as an indirect effect of TCs. The core element of this mechanism is a large moisture flux south of Kyushu, which is termed “moisture road,” and the difference from “atmospheric river” is discussed. This mechanism is not unique to Typhoon Maggie, as other cases of heavy rainfall in and around Kyushu are associated with similar situations.