論文 - 吉野　鉄大

Conference report: Fifth annual young researcher forum of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine

Yoshino T., Tanide S., Hamai M., Nishiura R., Hatae A., Nose I., Oda Y., Fukada Y., Yang X., Ando H., Ogawa K., Murakami K., Nakashima S.

Traditional and Kampo Medicine 12 （ 1 ） 74 - 79 2025年04月

　概要を見る

Seven young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan-yaku) at the Fifth Annual Young Researcher Forum held the day before the 2024 annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine. Ms Tanide presented on the changes in flavonoid and synephrine content in chimpi based on the storage period. Ms Hamai discussed natural compounds that contribute to improving bortezomib resistance in myeloma cells and their mechanisms of action. Ms Nishiura presented the production of a monoclonal antibody against geniposide and its application in indirect competitive enzyme-linked immunosorbent assay. Mr Hatae presented about the effects of ninjin'yoeito on cisplatin-induced anorexia and the variations in intestinal clock genes. Ms Nose explored the analgesic effects of bushi-containing Kampo formulas, with a focus on goshajinkigan's improvement of cold allodynia. Dr Oda discussed the antifungal activity of henna leaves against Malassezia. Lastly, Mr Fukuda presented how cultivation environments affect the quality of Schizonepeta spikes, including their morphology and component content. The event, conducted both in person and online, attracted a total of 54 participants. Looking ahead, we aim to further develop and continue hosting this forum in 2025 and beyond, fostering the advancement of research in this field.

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Survey of attitudes toward clinical research among Japanese traditional (Kampo) medicine specialists and certified doctors affiliated with the Japan Society for Oriental Medicine

Nogami T., Uneda K., Yoshino T., Ito H., Imoto S., Tahara E., Sunagawa M., Takayama S., Yakubo S., Mitani K.

Traditional and Kampo Medicine 12 （ 1 ） 27 - 37 2025年04月

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Aim: This study aims to assess the motivation, capability, and working environment of Japanese traditional (Kampo) medicine (JTM) specialists and certified physicians affiliated with the Japan Society for Oriental Medicine regarding clinical research. Their awareness and perception of COVID-19 studies and their interest in clinical research based on traditional JTM diagnostic concepts are explored. Methods: An online survey was conducted between May 20 and June 30, 2024, using Google Forms, targeting 2146 Japan Society for Oriental Medicine-certified JTM specialists and physicians. The survey covered their awareness of and participation in COVID-19 research, barriers to research, and educational needs for clinical researcher training. Results: In total, 570 participants (26.6%) responded, 44.1% of whom had more than 15 years of certification experience. Approximately 50% were unaware of the COVID-19 studies, and participation rates were low. The most common barriers to conducting clinical research included lack of time (58.1%), funding (54.8%), and research personnel (51.1%). In terms of educational needs, 74.3% of respondents expressed a need for statistical analysis training, and nearly 90% felt clinical research education should occur within 10 years of obtaining their medical licenses. Conclusion: This study reveals gaps in awareness and participation in clinical research among JTM specialists. Many respondents expressed willingness to engage in research; however, barriers such as limited time, funding, and personnel remain critical challenges. Furthermore, the need for specialized educational programs was strongly emphasized. Addressing these issues is essential for promoting clinical research in JTM.

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A Simulated Interprofessional Team Conference Using Cross-Training for Junior Healthcare Students in Interprofessional Education: a Qualitative Content Analysis

Tomisaki E., Haruta J., Horiguchi T., Arahata T., Fukui R., Uno S., Ando T., Yoshino T., Ishikawa S., Suzuki S., Yamaura K., Monkawa T.

Advances in Medical Education and Practice 16   583 - 594 2025年

ISSN  1179-7258

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Purpose: In 2021, we introduced a new simulation-based learning program focusing on a roleplay conference before patient discharge. This study aimed to evaluate the program’s effectiveness and highlight the significance of cross-training in interprofessional education (IPE). Methods: In September 2023, the program included 346 students (98 medical, 110 nursing, and 138 pharmacy students). The students’ reflective writing was analyzed using inductive content analysis to describe their learning and perspectives. The original items, subcategories, and main categories were extracted. The simulation involved the students role-playing various healthcare professionals during a discharge-planning conference for a stroke patient. This allowed them to experience the challenges and dynamics of interprofessional collaboration. Results: Student feedback emphasized the importance of understanding what constitutes a good healthcare team. A total of 203 items were grouped into eight main categories and 17 subcategories, including patient-centered care (related to the importance of patient-centered care, supporting patient decision-making, communicating with patients during conferences, and facilitating decision-making processes), contrasts in patient and interprofessional communication, conference communication (challenge of building consensus, the way to proceed conferences, importance of conference preparation, and process of information aggregation and realization of outcomes), mutual recognition and role contribution, building relationships (importance of daily interprofessional communication), understanding one’s profession (reflection on one’s own profession, understanding the roles of different professions, and communication within one’s own professional context), recursion into learning (motivation for continuous learning and improvement), and understanding other professions (understanding the role and perspectives of other professions and recognizing professional differences). Specific feedback highlighted improved empathy and communication skills. Students recognized the value of each profession’s contribution to patient care. Moreover, students reported a deeper appreciation of patient-centered approaches and the complexities of coordinating care across different healthcare roles. Conclusion: Simulated interprofessional team conferences using cross-training effectively taught junior students to understand the essence of a good healthcare team and the importance of a patient-centered approach. Cross-training significantly enhanced students’ interprofessional competencies, communication skills, and empathy toward other professions. This case underscores the necessity of incorporating cross-training into IPE to prepare healthcare professionals for collaborative practice and improve patient outcomes. Future research should consider expanding the scope to include more diverse scenarios and longitudinal assessments to measure longterm impacts on professional practice.

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Three Kampo medicines—bofutsushosan, boiogito, and daisaikoto—have different effects on host fat accumulation and the intestinal microbiota in a high-fat-diet–induced mouse model of obesity

Nakamichi K., Yoshino T., Akiyama M., Jibiki A., Yokoyama Y., Kawazoe H., Suzuki S., Watanabe K., Kim Y.G., Nakamura T.

Journal of Natural Medicines 2025年

ISSN  13403443

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Inhibiting body fat accumulation is important for the prevention of obesity. In Japan, three Kampo medicines are commonly used to treat obesity: bofutsushosan, boiogito, and daisaikoto. To compare the influences of these Kampo medicines on the intestinal microbiota, it is necessary to conduct a simultaneous investigation using the same mouse model under the same experimental conditions. C57BL/6J mice were divided into five groups: normal chow (NC), high-fat diet (HFD), HFD + 3% bofutsushosan extract (BTS), HFD + 3% boiogito extract (BOT), and HFD + 3% daisaikoto extract (DST). Epididymal white adipose tissue (WAT) weight, mesenteric WAT weight, serum triglyceride levels, and serum total cholesterol levels were measured. Additionally, total bacteria, alpha diversity, beta diversity, and bacterial composition in stool samples were measured. Body weight and epididymal WAT weight gain were significantly inhibited in the BTS-treated group and DST-treated group, but not in the BOT-treated group, compared with the HFD control group. Additionally, serum total cholesterol levels were significantly lower in the DST-treated group than in the HFD group. Specific intestinal bacteria, Clostridium sensu stricto 1, Erysipelatoclostridium, Roseburia, and the Lachnospiraceae NK4A136 group, were significantly changed in the Kampo-treated groups compared with the HFD group, and each of them was correlated with body weight gain, body fat rate, epididymal WAT weight, or mesenteric WAT weight. Our simultaneous investigation of BTS, BOT, and DST under the same conditions clearly demonstrated different changes in the intestinal microbiota and different effects on fat accumulation as well as their association among the three Kampo medicines.

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3-epi-18b-Glycyrrhetinic Acid or Its Glucuronide, the Metabolites of Glycyrrhizinic Acid with Individual Differences, Correlated with Diagnostic Marker for Licorice-Induced Pseudoaldosteronism in Humans

Sakoda R., Ishiuchi K., Yoshino T., Tsunoo Y., Namiki T., Ogawa-Ochiai K., Minamizawa K., Fukunaga K., Watanabe K., Makino T.

Drug Metabolism and Disposition 52 （ 12 ） 1407 - 1416 2024年12月

査読有り,  ISSN  00909556

　概要を見る

Licorice is a crude drug that is used in traditional Japanese Kampo medicine and is also used as a sweetener. Occasionally, it causes pseudoaldosteronism (PsA) as a side effect. The major symptoms include hypokalemia, hypertension, edema, and low plasma aldosterone levels. PsA might be caused by the metabolites of glycyrrhizinic acid (GL), a component of licorice. The development of PsA markedly varies among individuals; however, the factors that cause these individual differences remain unknown. In this study, 78 patients who consumed Kampo medicines containing licorice were enrolled, and their laboratory data, including serum potassium levels, plasma aldosterone concentrations (PAC), and the concentrations of GL metabolites in the residual blood and/or urine samples were evaluated. Of the 78 participants, 18b-glycyrrhetinic acid (GA), 3-epi-GA, 3-oxo-GA, 18b-glycyrrhetinyl-30-O-glucuronide (GA30G), and 3-epi-GA30G were detected in the serum samples of 65, 47, 63, 62, and three participants, respectively. Of the 29 urine samples collected, GA30G and 3-epi-GA30G were detected in 27 and 19 samples. 3-epi-GA30G is a newly found GL metabolite. Moreover, 3-epi-GA, 3-oxo-GA, and 3-epi-GA30G were identified in human samples for the first time. High individual differences were found in the appearances of 3-epi-GA in serum and 3-epi-GA30G in urine, and the concentrations of these metabolites were correlated with serum PsA markers. The inhibitory titers of 3-epi-GA, 3-oxo-GA, GA30G, and 3-epi-GA30G on human 11b-hydroxysteroid dehydrogenase type 2 were almost similar. These findings suggest that 3-epi-GA and/or 3-epi-GA30G are associated with individual differences in the development of PsA.

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Exploratory study of cold hypersensitivity in Japanese women: genetic associations and somatic symptom burden

Wu X., Yoshino T., Maeda-Minami A., Ishida S., Tanaka M., Nishi A., Tahara Y., Inami R., Sugiyama A., Horiba Y., Watanabe K., Mimura M.

Scientific Reports 14 （ 1 ） 1918 2024年12月

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Temperature perception is essential for humans to discern the environment and maintain homeostasis. However, some individuals experience cold hypersensitivity, characterized by a subjective feeling of coldness despite ambient environmental temperatures being normal, the underlying mechanisms of which are unknown. In this study, we aimed to investigate the relationship between subjective cold symptoms and somatic burden or single nucleotide polymorphisms to understand the causes of cold hypersensitivity. We conducted an online questionnaire survey [comprising 30 questions, including past medical history, subjective symptoms of cold hypersensitivity, and the Somatic Symptom Scale-8 (SSS-8)]. Respondents were 1200 Japanese adult female volunteers (age: 20–59 years), recruited between April 21 and May 25, 2022, who were customers of MYCODE, a personal genome service in Japan. Among the 1111 participants, 599 (54%) reported cold hypersensitivity. Higher cold hypersensitivity severity was positively associated with the SSS-8 scores. Additionally, a genome-wide association study for cold hypersensitivity was conducted using array-based genomic data obtained from genetic testing. We identified 11 lead variants showing suggestive associations (P < 1 × 10^–5) with cold hypersensitivity, some of which showed a reasonable change in expression in specific tissues in the Genotype-Tissue Expression database. The study findings shed light on the underlying causes of cold hypersensitivity.

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Current situation and future issues with Kampo medicine: A survey of Japanese physicians

Uneda K., Yoshino T., Ito H., Imoto S., Nogami T.

Traditional and Kampo Medicine 11 （ 2 ） 156 - 166 2024年08月

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Aim: We aimed to elucidate the present clinical situation, future challenges, and potential need for diagnostic support software in Kampo medicine. Methods: We conducted an online survey (comprising 28 questions) of Japanese physicians from the 23 to 24 January 2024 via MedPeer. The participants' responses were stratified according to their age distribution. Results: We evaluated data for 652 respondents. The most common respondent age groups were those in their 30s and 40s. The most common specialty of respondents was internal medicine (43.7%). Only 33.7% of respondents had received education on Kampo medicine at university. Most respondents (90.0%) were not licensed as certified physicians or members of the Japan Society for Oriental Medicine. Most respondents (86.7%) currently prescribed Kampo formulas (current users); only 3.8% had no experience in prescribing Kampo formulas. The conditions for which Kampo formulas were frequently prescribed were muscle cramps, constipation, medically unexplained symptoms/menopausal syndrome, appetite loss/malnutrition, and fatigue. However, 48.3% of current users did not use traditional Kampo patterns (sho). The most frequent issues reported by respondents were the lack of scientific evidence and standardization of diagnostic methods in Kampo medicine. Respondents indicated the need for postgraduate education and implementation of diagnostic support software for using Kampo patterns by non-specialists in Kampo medicine. Conclusion: There was a discrepancy between the high frequency of Kampo formula prescriptions and the low use of traditional Kampo patterns in Japan. Diagnostic support software is likely to become a useful method of improving appropriate Kampo formula prescriptions by non-specialists.

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Discrepancies of frequent symptoms in licorice-induced pseudoaldosteronism: A comparison of a systematic case review and the Ministry of Health, Labour and Welfare's manual

Hattori Y., Asano Y., Yoshino T.

Traditional and Kampo Medicine 11 （ 2 ） 167 - 169 2024年08月

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Background: Licorice-induced pseudoaldosteronism has been identified as a side effect of excessive licorice consumption. This condition is often characterized by hypertension, hypokalemia, and hyporeninemic hypoaldosteronism. If left untreated, this condition can lead to severe complications, such as arrhythmia and rhabdomyolysis, which can be life-threatening. Thus, it is critical to recognize the early symptoms of pseudoaldosteronism to facilitate prompt intervention and effective management. Here, we investigated the frequency of various accompanying symptoms by systematically reviewing case reports of licorice-induced pseudoaldosteronism not covered in similar studies and comparing findings with the manual on pseudoaldosteronism published by the Ministry of Health, Labour and Welfare (MHLW). Methods: A comprehensive search was conducted using MEDLINE/PubMed to gather relevant human studies published between 1960 and July 2023 and written in English; data focusing on accompanying symptoms were summarized. Results: Thirty-seven pertinent articles, encompassing 48 case reports (26 females and 1 unreported sex, mean age 64.6 ± 14.6), were identified and scrutinized. The analysis revealed that hypertension was the most prevalent followed by weakness and edema. None of the researched cases reported instances of spasticity or rigidity. Discussion: The study findings identified hypertension and weakness followed by edema as the predominant symptoms associated with pseudoaldosteronism which is in agreement with the MHLW manual. However, we doubt that spasticity, rigidity, and possibly numbness could be noticed by patients and their families as common initial symptoms outlined in the manual.

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Conference report: Fourth annual young researcher forum of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine

Yoshino T., Sakoda R., Nishihara M., Okayama M., Muraoka T., Yang X., Ando H., Nakashima S.

Traditional and Kampo Medicine 11 （ 1 ） 83 - 85 2024年04月

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Four young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan-yaku) at the Fourth Annual Young Researcher Forum held the day before the 2023 annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine. Mr Sakoda outlined his research plan, emphasizing the potential of yokukansan to enhance palliative care for cancer patients. Meanwhile, Ms Tanide and Mr Nishihara explored the correlation among component contents in Coptis japonica on Sado Island. Additionally, Mr Okayama presented his study, focusing on the use of Sinomenium acutum-derived compounds to inhibit the Wnt/β-catenin pathway and eradicate cancer stem cells. Finally, Mr Muraoka shared insights from his research on the inhibitory properties of Cassia obtusifolia sprout components. The event, conducted both in person and online, attracted a total of 58 participants. Looking ahead, we aim to further develop and continue hosting this forum in 2024 and beyond, fostering the advancement of research in this field.

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Machine learning model for predicting the cold–heat pattern in Kampo medicine: a multicenter prospective observational study

Maeda-Minami A., Yoshino T., Katayama K., Horiba Y., Hikiami H., Shimada Y., Namiki T., Tahara E., Minamizawa K., Muramatsu S.I., Yamaguchi R., Imoto S., Miyano S., Mima H., Uneda K., Nogami T., Fukunaga K., Watanabe K.

Frontiers in Pharmacology 15   1412593 - 1412593 2024年

ISSN  1663-9812

　概要を見る

Objective: The purpose of this study was to predict the four cold–heat patterns in patients who have the subjective symptoms of the cold–heat pattern described in the International Classification of Diseases Traditional Medicine Conditions – Module 1 by applying a machine learning algorithm. Methods: Subjects were first-visit Kampo outpatients at six institutions who agreed to participate in this multicenter prospective observational study. The cold pattern model and the heat pattern model were created separately with 148 symptoms, body mass index, blood pressure (systolic and diastolic), age, and sex. Along with a single cold or heat pattern, the tangled heat/cold pattern is defined as being predicted by both cold and heat patterns, while the moderate (heat/cold) pattern is defined as being predicted by neither the cold pattern nor the heat pattern. Results: We included 622 participants (mean age ±standard deviation, 54.4 ± 16.9; with female 501). The accuracy, macro-recall, precision, and F1-score of a combination of the two prediction models were 96.7%, 93.2%, 85.6%, and 88.5% respectively. The important items were compatible with the definitions of the cold–heat pattern. Conclusion: We developed a prediction model on cold–heat patterns with data from patients whose subjective cold/heat-related symptoms matched the cold–heat pattern diagnosis by the physician.

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Patient prognosis and prediction model for taking Kampo formulas in dysmenorrhea: An observational study

Maeda-Minami A., Kawamoto A., Yoshino T., Yokoyama Y., Suzuki S., Horiba Y., Nakamura T., Mimura M., Watanabe K.

Medicine United States 102 （ 48 ） e36191 2023年12月

ISSN  00257974

　概要を見る

Two representative Kampo formulas, keishibukuryogan and tokishakuyakusan, are frequently prescribed for patients with dysmenorrhea. We previously constructed a model that could predict which of these 2 formulas was most suitable, which is based on 4 subjective symptoms and 3 objective signs. To evaluate the prognosis of patients with dysmenorrhea using the established prediction model and assess the treatment outcomes between those treated in accordance with the prediction model and those who received various other treatments. In this retrospective, observational study, we included patients with menstrual pain who visited the Kampo Clinic at the Keio University Hospital for the first time between October 2014 and December 2020. These patients were monitored over a 90-day follow-up period. Participants were categorized into 2 groups: model-accordance and various-options. The progression of visual analogue scale (VAS) values was evaluated by determining the slopes from regression analysis between these 2 groups, with changes corroborated by the medical records. The study comprised 57 patients: 37 in the model-accordance group and 20 in the various-options group. Notably, the various-options group reported a significantly higher number of subjective symptoms (P = .03). The VAS value showed a decline, as indicated by the negative slope value of the regression line, across both groups - irrespective of their classification. There were no significant differences in the occurrence of adverse events between the 2 groups. The prognosis of patients with dysmenorrhea and the incidence of adverse events remained consistent, regardless of whether the treatment approach was in accordance with the prediction model or varied. Further studies are warranted to assess the prognosis when Kampo formulas are chosen based on the prediction model in the various-options population.

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A review of frequently used Kampo prescriptions. Part 3. Yokukansan

Yamaguchi H., Yoshino T., Oizumi H., Arita R., Nogami T., Takayama S.

Traditional and Kampo Medicine 10 （ 3 ） 197 - 223 2023年12月

　概要を見る

Background: The source of yokukansan (YKS) is thought to be Baoying-Jinjiang (Hoeikinkyōroku in Japanese) by Xue Ji. YKS was originally designed for children and indicated for spasms, clenching of teeth, digestive dysfunction due to mental instability, and insomnia. Key Findings: YKS formula consists of seven types of crude drugs. Clinical studies have revealed that YKS exerts physiological effects including the treatment of behavioral and psychiatric symptoms of dementia (BPSD), preoperative sedation and anxiety, and postoperative delirium. A meta-analysis showed that YKS could improve BPSD and daily living activities; however, no improvement in cognitive function was observed. Preclinical studies have also reported that YKS modulates neuronal pathways in the central nervous system, including the serotonergic, glutamatergic, GABAergic, and other neurotransmitter pathways. The incidence of adverse events associated with YKS was 5.17%, with the major adverse effect being pseudoaldosteronism. Routine blood sampling is considered for hypokalemia prevention. Conclusion: YKS is useful for BPSD and perioperative mental instability. The modulation of the serotonergic and glutamatergic neural pathways is one of mechanisms. Pseudoaldosteronism is one of the side effects.

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Development of a novel drug information provision system for Kampo medicine using natural language processing technology

Maeda-Minami A., Yoshino T., Yumoto T., Sato K., Sagara A., Inaba K., Kominato H., Kimura T., Takishita T., Watanabe G., Nakamura T., Mano Y., Horiba Y., Watanabe K., Kamei J.

BMC Medical Informatics and Decision Making 23 （ 1 ） 119 2023年12月

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Background: Kampo medicine is widely used in Japan; however, most physicians and pharmacists have insufficient knowledge and experience in it. Although a chatbot-style system using machine learning and natural language processing has been used in some clinical settings and proven useful, the system developed specifically for the Japanese language using this method has not been validated by research. The purpose of this study is to develop a novel drug information provision system for Kampo medicines using a natural language classifier® (NLC®) based on IBM Watson. Methods: The target Kampo formulas were 33 formulas listed in the 17th revision of the Japanese Pharmacopoeia. The information included in the system comes from the package inserts of Kampo medicines, Manuals for Management of Individual Serious Adverse Drug Reactions, and data on off-label usage. The system developed in this study classifies questions about the drug information of Kampo formulas input by natural language into preset questions and outputs preset answers for the questions. The system uses morphological analysis, synonym conversion by thesaurus, and NLC®. We fine-tuned the information registered into NLC® and increased the thesaurus. To validate the system, 900 validation questions were provided by six pharmacists who were classified into high or low levels of knowledge and experience of Kampo medicines and three pharmacy students. Results: The precision, recall, and F-measure of the system performance were 0.986, 0.915, and 0.949, respectively. The results were stable even with differences in the amount of expertise of the question authors. Conclusions: We developed a system using natural language classification that can give appropriate answers to most of the validation questions.

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Contribution of traditional Japanese Kampo medicines, kakkonto with shosaikotokakikyosekko, in treating patients with mild-to-moderate coronavirus disease 2019: Further analysis of a multicenter, randomized controlled trial

Takayama S., Namiki T., Arita R., Ono R., Kikuchi A., Ohsawa M., Saito N., Suzuki S., Nakae H., Kobayashi S., Yoshino T., Ishigami T., Tanaka K., Takagi A., Yamaguchi T., Ishii T., Hisanaga A., Mitani K., Ito T.

Journal of Infection and Chemotherapy 29 （ 11 ） 1054 - 1060 2023年11月

ISSN  1341321X

　概要を見る

We previously reported the finding of symptom relief in a randomized controlled trial with the combined use of kakkonto and shosaikotokakikyosekko added to conventional treatment in patients with coronavirus disease 2019 (COVID-19). For further evaluation, we performed post hoc analysis focused on symptom disappearance without recurrence, to determine a clearer effect of Kampo medicine. Patients with mild and moderate COVID-19 were randomly allocated to a control group receiving symptomatic therapy or a Kampo group receiving kakkonto (2.5 g) with shosaikotokakikyosekko (2.5 g) three times daily in addition to symptomatic therapy. The data of 161 patients (Kampo group, n = 81; control group, n = 80) were analyzed post hoc for the time to symptom disappearance. Kaplan-Meier and Cox proportional hazard estimates of disappearance of symptoms showed that all and each symptom targeted in this study disappeared faster in the Kampo group than in the control group, although not statistically significant (all symptomatic cases; hazard ratio [HR] 3.73, 95% confidence interval [CI] 0.46−29.98, log-rank p = 0.1763). In a supplemental assessment using covariate adjustment and competing risk analysis, fever disappeared faster in the Kampo group than in the control group (all symptomatic cases, HR 1.62, 95% CI 0.99−2.64, p = 0.0557; unvaccinated cases, HR 1.68, 95% CI 1.00−2.83, p = 0.0498) and shortness of breath disappeared significantly faster in Kampo group than in control group (all symptomatic cases, HR 1.92, 95% CI 1.07−3.42, p = 0.0278; unvaccinated cases, HR 2.15, 95% CI 1.17−3.96, p = 0.0141). These results demonstrate the advantages of Kampo treatment for acute COVID-19.

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The Integration of Traditional Medicine with Conventional Biomedicine: A Narrative Review of the Japanese Perspective

Yoshino T., Kashio A., Terasawa Y., Hachiki M., Yoshinaga R., Arita R.

Journal of Integrative and Complementary Medicine 29 （ 6-7 ） 372 - 379 2023年07月

ISSN  27683605

　概要を見る

Objectives: This is a narrative review of the integration of traditional medicine with conventional biomedicine in present day Japan, whose aging population is considered one of the largest globally. Design: It is focused on the aging population because this age group most avails of healthcare. We also tried to describe the unique Japanese medical situations, clinical outcome of Japanese traditional medicine (Kampo medicine) which may include acupuncture, and education of Kampo medicine workforce. Results: Conventional schools of medicine in Japan are required to teach Kampo medicine, and most Japanese physicians (>80%) prescribe traditional medicine, especially in primary care settings. The universal national healthcare system covers Kampo medicine prescribed by physicians and treatment by acupuncturists (they sometimes refer patients who may need evaluation by physicians), enhancing access to primary healthcare. Additionally, pharmacists who graduated from conventional schools of pharmacy also select and sell Kampo medicine as over-the-counter (OTC) medication. Kampo medicine available as prescription drugs and OTC is effective, and has been proven to be economically beneficial in several clinical settings. Conclusions: An aging population is a global concern for both developed and developing countries. Japan, having a significantly-large aging population, integrates conventional biomedicine and traditional medicine in its universal national healthcare coverage, through its biomedically-trained physicians and pharmacists who also learned traditional medicine, as well as the acupuncturists. By reviewing the current situation in Japan, the authors hope to introduce the future of the global contribution of traditional, complementary, and integrative medicine in primary care.

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Conference report: Third annual young researcher forum of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine

Yoshino T., Yokogawa T., Nakamichi K., Manse Y., Yoshikawa H., Sasaki H., Ando H., Nakashima S.

Traditional and Kampo Medicine 10 （ 1 ） 78 - 81 2023年04月

　概要を見る

Four young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan-yaku) at the third annual young researcher forum entitled “Respecting and Breaking Traditions,” held 1 week before the 2022 annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine. Dr. Yokogawa presented her research focusing on the mechanism of the Ayurveda drug-eluting string, Kshara Sutra, in treating anal fistulas, reporting on its effects on the anal tissue in an anal fistula rat model and its antibacterial activity against Escherichia coli and Staphylococcus aureus, the causative organisms of anal fistulas. Mr. Nakamichi presented his research focusing on the relationship between the efficacy of Kampo medicines with anti-obesity effects and intestinal microbiota composition. His results partially revealed that bofutsushosan and boiogito affect lipid metabolism in mice and correlate with the intestinal microbiota composition. Dr. Manse reported the anti-inflammatory activity of diterpenoid components in Enmei-so (Isodonis Herba), revealing its novel inhibitory activity on nitric oxide released from activated macrophages and on inflammatory cytokines, and identified active components contributing to the inhibition and the mechanism of action. Mr. Yoshikawa reported the anticancer activity of small molecular compounds isolated from the medicinal plants, Valeriana fauriei and Hypericum erectum. His results suggest that five compounds may increase the sensitivity of human cervical carcinoma cells to adriamycin via HSP105 expression suppression. The event was conducted online, and included 78 participants. We intend to hold and improve this forum in 2023 and the future.

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To whom the side effect of licorice, pseudoaldosteroneism, will occur: case-control study.

Tetsuhiro Yoshino, Komatsu, Akihiro, Nakamura, Tomonori and Watanabe, Kenji

2023年03月

　概要を見る

Background: Pseudoaldosteronism is a well-known side effect of licorice or glycyrrhizin (GL), one of major components in licorice. Pseudoaldosteronism mimics primary aldosteronism which causes hypokalemia, hypertension, and extremities’ edema. GL can be used to treat chronic hepatitis, but also plays important role in pseudoaldosteronism. The importance of multidrug resistance protein 2 (Mrp2) in GL excretion has been reported recently. Dysfunction of Mrp2 causes elevated direct bilirubin (DB), GL, and its metabolites. Hence, elevated DB can be a risk predictor of pseudoaldosteronism. The relationship between pseudoaldosteronism and elevated DB, however, has not been studied as yet. Objectives: To evaluate the relationship between elevated DB and hypokalemia, the most sensitive marker of pseudoaldosteronism.

Sigmoid Volvulus

Yoshino T., Hiruma H.

Annals of Internal Medicine Clinical Cases 2 （ 12 ）  2023年

　概要を見る

An 83-year-old woman who resided in a nursing home presented to the emergency department with abdominal pain and vomiting resulting in the diagnosis of sigmoid volvulus. She needed intermittent catheter reduction of the colonic air but no surgical intervention has been performed so far.

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Conventional and Kampo Medicine Treatment for Mild-to-moderate COVID-19: A Multicenter, Retrospective, Observational Study by the Integrative Management in Japan for Epidemic Disease (IMJEDI Study-observation)

Takayama S., Yoshino T., Koizumi S., Irie Y., Suzuki T., Fujii S., Katori R., Kainuma M., Kobayashi S., Nogami T., Yokota K., Yamazaki M., Minakawa S., Chiba S., Suda N., Nakada Y., Ishige T., Maehara H., Tanaka Y., Nagase M., Kashio A., Komatsu K., Nojiri M., Shimooki O., Nakamoto K., Arita R., Ono R., Saito N., Kikuchi A., Ohsawa M., Nakae H., Mitsuma T., Mimura M., Ishii T., Nochioka K., Chiu S.W., Yamaguchi T., Namiki T., Hisanaga A., Mitani K., Ito T.

Internal Medicine 62 （ 2 ） 187 - 199 2023年

ISSN  09182918

　概要を見る

Objective Patients in whom coronavirus disease 2019 (COVID-19) was suspected or confirmed between January 1, 2020, and October 31, 2021, were enrolled from Japanese hospitals in this multicenter, retrospective, observational study. Methods Data on the treatment administered (including conventional and Kampo medicine) and changes in common cold-like symptoms (such as fever, cough, sputum, dyspnea, fatigue, and diarrhea) were collected from their medical records. The primary outcome was the number of days without a fever (with a body temperature <37°C). The secondary outcomes were symptomatic relief and the worsening of illness, defined as the presence of a condition requiring oxygen inhalation. The outcomes of patients treated with and without Kampo medicine were compared. Patients We enrolled 962 patients, among whom 528 received conventional and Kampo treatment (Kampo group) and 434 received conventional treatment (non-Kampo group). Results Overall, after adjusting for the staging of COVID-19 and risk factors, there were no significant between-group differences in the symptoms or number of days being afebrile. After performing propensity score matching and restricting the included cases to those with confirmed COVID-19 who did not receive steroid administration and initiated treatment within 4 days from the onset, the risk of illness worsening was significantly lower in the Kampo group than in the non-Kampo group (odds ratio=0.113, 95% confidence interval: 0.014-0.928, p=0.0424). Conclusion Early Kampo treatment may suppress illness worsening risk in COVID-19 cases without steroid use. Further randomized controlled studies are needed to confirm the clinical benefit of Kampo medicine for COVID-19.

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Multicenter, randomized controlled trial of traditional Japanese medicine, kakkonto with shosaikotokakikyosekko, for mild and moderate coronavirus disease patients

Takayama S., Namiki T., Arita R., Ono R., Kikuchi A., Ohsawa M., Saito N., Suzuki S., Nakae H., Kobayashi S., Yoshino T., Ishigami T., Tanaka K., Nochioka K., Takagi A., Mimura M., Yamaguchi T., Ishii T., Hisanaga A., Mitani K., Ito T.

Frontiers in Pharmacology 13   1008946 2022年11月

ISSN  1663-9812

　概要を見る

The traditional Japanese (Kampo) medicine, kakkonto with shosaikotokakikyosekko, has antiviral and anti-inflammatory effects. In this randomized trial, patients with mild and moderate coronavirus disease (COVID-19) were randomly allocated to the control group receiving conventional treatment for symptom relief such as antipyretics and antitussives or the Kampo group receiving mixed extract granules of kakkonto (2.5 g) and shosaikotokakikyosekko (2.5 g) three times a day for 14 days in addition to conventional treatment. The main outcome was the number of days until total symptom relief. The secondary outcome was the number of days until each symptom’s relief and whether the disease progressed to respiratory failure. We enrolled a total of 161 patients (Kampo group, n = 81; control group, n = 80). The results from Kaplan–Meier estimates of symptom relief showed that there are no significant differences between the groups. However, covariate-adjusted cumulative incidence of fever relief considering competitive risk showed that the recovery was significantly faster in the Kampo group than in the control group (HR 1.76, 95% CI 1.03–3.01). Additionally, the risk of disease progression to moderate COVID-19 requiring oxygen inhalation was lower in the Kampo group than in the control group (Risk Difference −0.13, 95% CI −0.27–0.01). No significant drug-related side effects were observed. Kakkonto with shosaikotokakikyosekko is effective for fever relief with suppression of disease progression in COVID-19 patients. Clinical Trial Registration: https://jrct.niph.go.jp/en-latest-detail/jRCTs021200020, identifier [jRCTs021200020]

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Exploring Standardized Scales and Serum Biomarkers to Evaluate Changes in Pruritus due to Eczema after Japanese Kampo Treatment: A Prospective Case Series

Yoshino T., Horiba Y., Mimura M., Watanabe K.

Complementary Medicine Research 29 （ 5 ） 373 - 380 2022年10月

ISSN  25042092

　概要を見る

Background: We aimed to explore standardized scales and serum biomarkers for tracking changes in the symptoms and severity of pruritus due to eczema in patients treated with Kampo formulas. Patients and Methods: This prospective, single-arm, pre-post comparison case series recruited patients with pruritus mostly due to eczema who consulted the Kampo Clinic at the Keio University Hospital from June 2019 to March 2020. The participants were prescribed a personalized Kampo formula for 12 weeks. Patient profiles and symptoms were assessed every 4 weeks using the visual analog scale (VAS), patient-oriented eczema measure (POEM) scale, 5-D itch scale (5D), Skindex-16, and eczema area and severity index (EASI). Blood biomarkers and intestinal permeability indicators were measured at the first consultation and 12 weeks later. Results: Pruritus and eczema severity improved significantly over time. The VAS, POEM, 5D, and Skindex-16 scores were well-correlated. The serum interleukin-31 levels decreased significantly after a 12-week intervention. Changes in the interleukin-31 level correlated with the diamine oxidase level at week 0, suggesting the involvement of the Th2 immune system and intestinal permeability in the mechanism of Kampo formulas. Conclusion: The evaluated scales are suitable for evaluating subjective symptoms and eczema severity after Kampo treatment; further studies are required to verify the study findings.

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Climacteric symptoms in postoperative patients among endometrial cancer, cervical cancer, and ovarian cancer: a cross-sectional study

Horiba Y., Yoshino T., Yokota M., Iwata T., Watanabe K., Mimura M., Aoki D.

Supportive Care in Cancer 30 （ 8 ） 6785 - 6793 2022年08月

ISSN  09414355

　概要を見る

Purpose: To date, no studies have assessed climacteric symptoms after hystero-adnexectomy for endometrial, cervical, or ovarian cancer. Thus, this study aimed to compare climacteric symptoms among patients who underwent surgery for these three cancer types. Methods: In this cross-sectional study, we interviewed patients who were registered at a menopausal outpatient clinic between January 1999 and July 2016 after undergoing total hysterectomy, intrapelvic only or intrapelvic plus para-aortic lymph node dissection, and bilateral adnexectomy performed via laparotomy as a cancer treatment. Climacteric symptoms were assessed using a patient-reported questionnaire covering core domains with five symptoms only at the initial consultation. Each symptom was graded from 0 (no symptoms) to 3 (severe symptoms). We evaluated the frequency of symptom severity according to the time elapsed since surgery and the cancer type. Results: The numbers of patients with endometrial, ovarian, and cervical cancer were 328, 90, and 107, respectively. Overall, climacteric symptoms were more severe in patients with cervical cancer than in those with endometrial or ovarian cancer; symptom severity decreased with increasing time since surgery. However, symptom severity did not decrease significantly over time in patients with cervical cancer even after > 5 years had elapsed since surgery. Conclusion: The climacteric symptoms were less severe in patients with endometrial or ovarian cancer with longer time elapsed since surgery but not in those with cervical cancer. Patients with cervical cancer may require more prompt interventions, including symptomatic treatment and longer follow-up period, than those with endometrial or ovarian cancer.

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Conference report: Second annual young researcher forum of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine

Yoshino T., Yoneda T., Yang X., Nishihara M., Ogawa K., Kitamura M., Ando H., Nakashima S., Horie I.

Traditional and Kampo Medicine （Wiley）  9 （ 2 ） 144 - 147 2022年08月

　概要を見る

Five young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan-yaku) at the second annual young researcher forum entitled “Growing Research Buds by Young Investigators,” held during the annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine 2021. Mr. Yoneda presented exploratory research on new pharmaceutical seed compounds from garlic (Allium sativum). Dr. Yang investigated whether diosgenin promoted proper axonal regeneration in the brain using a mouse model of Alzheimer's disease. Her study clarified the molecular mechanisms of the diosgenin-driven accurate pathfinding of injured axons. Mr. Nishihara presented his research on promoting the effective utilization of Phellodendron trees in Nara Prefecture. His research team evaluated the possibility of short-term cultivation, screened for useful components in the leaves. Dr. Ogawa used the Japanese Adverse Drug Event Report (JADER) database, which contains reports of side effects associated with drug treatment, to demonstrate the effectiveness of hokizai in reducing side effects, particularly those of anticancer drugs. Dr. Kitamura reported that Cnidium monnieri (L.) Cusson fruit extract and the isolated active ingredients, osthol and imperatorin, strongly inhibited the activity of furin-like enzymes. Further screening indicated that root extracts of Paeonia lactiflora Pall. and Scutellaria baicalensis Georgi suppressed cell syncytial formation by the S protein. The event was held online, and we had 86 participants. We can improve this forum in terms of format, frequency, and publicity activities; however, we hope to hold this forum in 2022 and in the future.

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A prediction model of qi stagnation: A prospective observational study referring to two existing models

Maeda-Minami A., Ihara K., Yoshino T., Horiba Y., Mimura M., Watanabe K.

Computers in Biology and Medicine 146   105619 2022年07月

ISSN  00104825

　概要を見る

Objective: To establish a prediction model of qi stagnation referring to two existing models. Design: Prospective observational study. Setting: We recruited patients who visited the Kampo Clinic at Keio University from February 2011 to March 2013. Methods: We constructed a random forest algorithm with 202 items as independent variables to predict qi stagnation patterns using full agreement data of the physicians’ diagnosis and the result of two existing scores as a reference standard. To compare the new model with the two existing models, we calculated the discriminant ratio (prediction accuracy), precision, sensitivity (recall), specificity, and F-measure of these models. Results: The number of eligible participants was 1,194, and 29.1% of them were diagnosed with qi stagnation by Kampo physicians. The discriminant ratio, precision, sensitivity, specificity, and F-measure in our new model were 0.960, 0.672, 0.911, 0.964, and 0.774, respectively. Our new model had a significantly higher discriminant ratio than the two existing models. Conclusions: We constructed a better qi stagnation prediction model than the previously established ones. Our results can be utilized to reach an international agreement on qi stagnation pattern diagnosis in traditional East Asian medicine.

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Oral Astragalus Root Supplementation for Mild to Moderate Chronic Kidney Disease: A Self-Controlled Case-Series

Yoshino T., Horiba Y., Mimura M., Watanabe K.

Frontiers in Pharmacology 13   775798 2022年03月

ISSN  16639812

　概要を見る

In this self-controlled case series, we aimed to investigate the variation in estimated glomerular filtration rate (eGFR) after taking astragalus-containing preparations in patients with mild to moderate chronic kidney disease (CKD) by retrospectively reviewing their charts in our clinic. We set the inclusion criteria as first-visit patients aged 20 years or older presenting to our clinic between 1 October 2014, and 31 June 2019, and who were prescribed astragalus-containing herbal preparations for any reason. We calculated the mean eGFR from the readings taken 6 months before (pre) and after (post) the intake of astragalus-containing preparations for each participant. Among the 37 patients included in our final analysis, we found a statistically significant improvement in the eGFR after prescribing astragalus-containing preparations (pre, 66 ± 12 ml/min/1.73 m² vs. post, 70 ± 14 ml/min/1.73 m²; p < 0.001 by paired t-test). Our results were consistent regardless of age, sex, CKD stage of the participants (G2 or G3), daily dosage of astragalus root, or duration of astragalus-containing preparations. No severe adverse reactions were recorded in the charts of the study participants. Our results suggest that there is eGFR improvement after taking astragalus-containing preparations in mild to moderate CKD cases as reported previously. The findings should be considered with caution due to major limitations such as small sample size without optimum control, short follow-up period, and incomplete data. Further adequately powered and designed studies are needed to confirm the efficacy and safety of the long-term use of astragalus root in patients with mild to moderate CKD.

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総合診療病棟　大柴胡湯去大黄による薬剤性間質性肺炎を早期診断加療し、救命できた1例

石田 洋子, 吉野 鉄大, 正木 克宜, 渡辺 賢治, 福永 興壱

総合診療 （(株)医学書院）  32 （ 2 ） 252 - 255 2022年02月

ISSN  2188-8051

　概要を見る

症例は76歳男性で、某年X月に39℃超の発熱が出るようになった。2週間後に呼吸困難が出現し、階段昇降時などの労作で症状が悪化した。咳嗽や喀痰は認めなかった。X+1月に夜間就寝中に強い呼吸困難が出現したため救急要請し、低酸素血症と両側肺野の浸潤影があり、肺炎の診断で緊急入院となった。入院時のCTで両側肺野にび漫性にすりガラス陰影と小葉間隔壁の肥厚を認めた。血液ガス所見ではI型呼吸不全を認めた。各種検査結果と経過も合わせて、薬剤性間質性肺炎およびその急性増悪が疑われた。被疑薬である大柴胡湯去大黄を中止した。予断を許さない呼吸状態であったため、第1病日からm-PSL 1000mg/日のステロイドパルスを3日間施行した。第4病日よりPSL 65mg/日(1mg/kg/日)を開始し、以降は第11病日よりPSL 60mg/日、第18病日よりPSL 50mg/日と漸減した。入院時にはリザーバーマスク15L/分で使用していた酸素需要は漸減し、第8病日には酸素投与不要となった。呼吸不全の悪化リスクがあり、気管支鏡検査は実施できなかったが、後日結果が判明した薬剤誘発性リンパ球刺激試験で大柴胡湯去大黄が陽性であり、経過なども踏まえて総合的に、漢方薬による薬剤性間質性肺炎と診断した。第19病日に独歩退院となった。

Climacteric symptoms in postoperative patients among endometrial cancer, cervical cancer, and ovarian cancer: A cross-sectional study

Horiba, Y. and Yoshino, T. and Yokota, M. and Iwata, T. and Watanabe, K. and Mimura, M. and Aoki, D.

ResearchSquare 2022年

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Relationship Between Conventional Medicine Chapters in ICD-10 and Kampo Pattern Diagnosis: A Cross-Sectional Study

Wu X., Le T.K., Maeda-Minami A., Yoshino T., Horiba Y., Mimura M., Watanabe K.

Frontiers in Pharmacology （Frontiers in Pharmacology）  12   751403 2021年12月

ISSN  16639812

　概要を見る

Objectives: The newest revision to the International Classification of Diseases, the 11th edition (ICD-11) includes disease classifications from East Asian medicine, including traditional Japanese medicine (Kampo medicine). These disease classifications allow for comparisons between disease classifications from conventional medicine and Kampo medicine. Design/Location/Subjects/Interventions: This is an exploratory, cross-sectional study exploring the relationship between conventional medicine diagnoses and Kampo medicine diagnoses at a large Kampo clinic in Japan. Patients were seen from October 1st, 2014 to June 30th, 2019 and were 20 years of age or older. Outcome measures: Patients presented with one or more conventional medicine ICD-10 codes into the clinic and were given one descriptor from the ICD-11 within the heat-cold module, excess-deficiency module, and an optional body constituents module. The distribution of these Kampo medicine codes was examined in relation to conventional medicine chapters. Results: 1,209 patients were included in our final analysis. Patient number, ages, sex ratio, and BMI varied within conventional medicine ICD-10 chapters and Kampo medicine descriptor codes. Certain conventional medicine chapters are related to specific Kampo medicine descriptor codes, such as chapter IV (endocrine, nutritional, and metabolic diseases) with excess, heat, and kidney qi deficiency. Conclusion: The advent of the ICD-11 allows for systematic, standardized comparisons between Kampo medicine, and contemporary medicine. In this exploratory study, our findings support the independence of Kampo medicine pattern descriptors with ICD-10 conventional medicine chapters. Code overrepresentations in relation to conventional medicine diseases and by age and sex should be an area of future investigation to best understand how to synergize and improve patient care.

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Clinical Risk Factors of Licorice-Induced Pseudoaldosteronism Based on Glycyrrhizin-Metabolite Concentrations: A Narrative Review

Yoshino T., Shimada S., Homma M., Makino T., Mimura M., Watanabe K.

Frontiers in Nutrition （Frontiers in Nutrition）  8   719197 2021年09月

ISSN  2296861X

　概要を見る

Licorice, the dried root or stolon of Glycyrrhiza glabra or G. ularensis, is commonly used worldwide as a food sweetener or crude drug. Its major ingredient is glycyrrhizin. Hypokalemia or pseudoaldosteronism (PsA) is one of the most frequent side effects of licorice intake. Glycyrrhizin metabolites inhibit type 2 11β-hydroxysteroid dehydrogenase (11βHSD2), which decomposes cortisol into inactive cortisone in the distal nephron, thereby inducing mineralocorticoid receptor activity. Among the several reported glycyrrhizin-metabolites, 18β-glycyrrhetyl-3-O-sulfate is the major compound found in humans after licorice consumption, followed by glycyrrhetinic acid. These metabolites are highly bound to albumin in blood circulation and are predominantly excreted into bile via multidrug resistance-associated protein 2 (Mrp2). High dosage and long-term use of licorice are constitutional risk factors for PsA. Orally administered glycyrrhizin is effectively hydrolyzed to glycyrrhetinic acid by the intestinal bacteria in constipated patients, which enhances the bioavailability of glycyrrhizin metabolites. Under hypoalbuminemic conditions, the unbound metabolite fractions can reach 11βHSD2 at the distal nephron. Hyper direct-bilirubin could be a surrogate marker of Mrp2 dysfunction, which results in metabolite accumulation. Older age is associated with reduced 11βHSD2 function, and several concomitant medications, such as diuretics, have been reported to affect the phenotype. This review summarizes several factors related to licorice-induced PsA, including daily dosage, long-term use, constipation, hypoalbuminemia, hyper direct-bilirubin, older age, and concomitant medications.

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Inter-Rater Reliability of Kampo Diagnosis for Chronic Diseases

Maeda-Minami A., Yoshino T., Horiba Y., Nakamura T., Watanabe K.

Journal of Alternative and Complementary Medicine （Journal of Alternative and Complementary Medicine）  27 （ 7 ） 613 - 616 2021年07月

ISSN  10755535

　概要を見る

This single-center observational study aimed to assess the inter-rater reliability (IRR) of Kampo medicine pattern diagnosis, which is modularized into three modules for chronic diseases, using 64 participants' information documents. The linearly weighted percentage of agreement and Gwet's agreement coefficient (AC) 2 for the deficiency-excess module, among three specialists, were 85.9% and 0.708, respectively. The unweighted percentage of agreement and Gwet's AC1 were 64.6% and 0.542 for the cold-heat, and 35.9% and 0.254 for the qi-blood-fluid modules, respectively. Our findings suggest that our modularization method may improve the IRR of Kampo medicine pattern diagnosis.

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不登校の孫と易疲労の祖母に柴胡加竜骨牡蛎湯が奏効した症例

沢井 かおり, 吉野 鉄大, 大岸 美和子, 渡辺 賢治

日本東洋医学雑誌 （(一社)日本東洋医学会）  72 （ 3 ） 235 - 238 2021年07月

ISSN  0287-4857

　概要を見る

漢方治療では、異なる病状の症例でも漢方的病態が同じであれば同一処方が有効であり、これを異病同治と称する。特に家族では、遺伝的素因や生活環境の共通性から漢方的病態が類似しやすい。今回、不登校の孫と易疲労の祖母に対する異病同治の症例を経験したので報告する。症例1(孫)は13歳女性、主訴は不登校である。やや実証、寒熱中間証、気逆、気滞、血虚と診断して柴胡加竜骨牡蛎湯を処方したところ、次第に登校できるようになり、集中力がついて成績もよくなった。症例2(祖母)は73歳女性、主訴は易疲労である。虚実中間証、寒熱中間証、気滞、気虚と診断して柴胡加竜骨牡蛎湯を処方したところ、体調がよくなり元気になった。不登校の孫と易疲労の祖母に対して、柴胡加竜骨牡蛎湯がいずれも奏効した。これは血縁であるということと、家庭内のトラブルという背景の一致によって、漢方的病態が似ていたためと思われた。(著者抄録)

Identification of an Alternative Glycyrrhizin Metabolite Causing Liquorice-Induced Pseudohyperaldosteronism and the Development of ELISA System to Detect the Predictive Biomarker

Ishiuchi K., Morinaga O., Yoshino T., Mitamura M., Hirasawa A., Maki Y., Tashita Y., Kondo T., Ogawa K., Lian F., Ogawa-Ochiai K., Minamizawa K., Namiki T., Mimura M., Watanabe K., Makino T.

Frontiers in Pharmacology （Frontiers in Pharmacology）  12   688508 - 688508 2021年05月

ISSN  16639812

　概要を見る

Liquorice is usually used as crude drug in traditional Japanese Kampo medicine and traditional Chinese medicine. Liquorice-containing glycyrrhizin (GL) can cause pseudohyperaldosteronism as a side effect. Previously, we identified 18β-glycyrrhetyl-3-O-sulfate (3) as a GL metabolite in Eisai hyperbilirubinuria rats (EHBRs) with the dysfunction of multidrug resistance-related protein (Mrp2). We speculated that 3 was associated with the onset of liquorice-induced pseudohyperaldosteronism, because it was mainly detected in serum of patients with suspected to have this condition. However, it is predicted that other metabolites might exist in the urine of EHBRs orally treated with glycyrrhetinic acid (GA). We explored other metabolites in the urine of EHBRs, and investigated the pharmacokinetic profiles of the new metabolite in EHBRs and normal Sprague-Dawley rats. We further analyzed the serum concentrations of the new metabolite in the patients of pseudohyperaldosteronism. Finally, we developed the analyzing method of these metabolites as a preventive biomarker for the onset of pseudohyperaldosteronism using an enzyme-linked immunosorbent assay (ELISA). We isolated a new GL metabolite, 18β-glycyrrhetyl-3-O-sulfate-30-O-glucuronide (4). Compound 4 significantly inhibited rat type-2 11β-hydroxysteroid dehydrogenase (11β-HSD2) and was a substrate of both organic anion transporter (OAT) 1 and OAT3. Compound 4 was also detected in the serum of patients with suspected pseudohyperaldosteronism at an approximately 10-fold lower concentrations than 3, and these concentrations were positively correlated. Compound 4 showed a lower serum concentration and weaker inhibitory titer on 11β-HSD2 than 3. We developed an enzyme-linked immunosorbent assay system using an anti-18β-glycyrrhetyl-3-O-glucuronide (3MGA) monoclonal antibody to measure the serum concentration of 3 to facilitate the measurement of biomarkers to predict the onset of pseudohyperaldosteronism. Although we found 4 as the secondary candidate causative agent, 3 could be the main potent preventive biomarker of liquorice-induced pseudohyperaldosteronism. Compound 3 was detected in serum at a higher concentration than GA and 4, implying that 3 may be a pharmacologically active ingredient mediating not only the development of pseudohyperaldosteronism but anti-inflammatory effects in humans administered GL or other liquorice-containing preparations.

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Conventional and Kampo medicine in the treatment of mild to moderate COVID-19: A multicenter, retrospective observational study protocol by the Integrative Management in Japan for Epidemic Disease (IMJEDI study-Observation)

Takayama S., Kashima M., Namiki T., Ito T., Ono R., Arita R., Saito N., Nakae H., Irie Y., Kobayashi S., Yoshino T., Ishigami T., Tanaka K., Nogami T., Minakawa S., Nagase M., Kashio A., Ishige T., Maehara H., Saito T., Sempuku S., Yamazaki M., Tahara E., Suda N., Nakamoto K., Mitsuma T., Sato H., Shimooki O., Nakada Y., Abe S., Masuda T., Kai H., Yokota K., Chiba S., Saitoh F., Tanaka Y., Koizumi S., Fujii S., Katori R., Kainuma M., Nochioka K., Chiu S.W., Kikuchi A., Suzuki T., Mimura M., Yamaguchi T., Ishii T.

Traditional and Kampo Medicine 8 （ 1 ） 106 - 110 2021年04月

　概要を見る

Aim: We present the study protocol of a multicenter, retrospective observational study that aims to investigate the efficacy of the actual treatment (the efficacy of conventional and Kampo medicines) of patients with mild to moderate or suspected coronavirus disease (COVID-19). Methods: This study is designed as a multicenter, retrospective observational study. Outpatients and inpatients will be recruited from Japanese hospitals. The inclusion criteria are as follows: having or suspected to have COVID-19, mild to moderate COVID-19, symptomatic, ≥20 years of age, male or female, able to communicate in Japanese, and treated with conventional and Kampo medicine. The exclusion criteria are: unable to provide informed consent due to dementia, psychosis, or psychiatric symptoms, severe COVID-19, or determined unsuitable for this study. The sample size is set at 1000, as this number of people can be treated at the collaborating medical institutions during the study period. Results: The main outcome is the number of days without fever, with a body temperature of less than 37°C. The secondary outcome is set at common cold-like symptoms other than fever (fatigue, cough, shortness of breath, sputum, diarrhea) and severity of illness and hospitalization up to 14 days after the visit. Trial registration: The trial was registered in the University Hospital Medical Information Network (Reservation No. UMIN000041301) on August 4, 2020. Conclusion: Our study will explore the contribution of conventional and Kampo medicine in the treatment of patients with mild and moderate COVID-19.

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Bilateral pneumothorax after acupuncture treatment

Nishie M., Masaki K., Kayama Y., Yoshino T.

BMJ Case Reports （BMJ Case Reports）  14 （ 3 ）  2021年03月

ISSN  1757790X

　概要を見る

A 31-year-old female physician was diagnosed with bilateral pneumothorax a day after her acupuncture treatment. Her body mass index was 16.9 and she did not have a prior history of respiratory disease or smoking. Acupuncture needles may easily reach the pleura around the end of the suprascapular angle of the levator scapulae muscle where the subcutaneous tissue is anatomically thin. In our patient, the thickness between the epidermis and the visceral pleura in this area was only 22 mm as confirmed by an ultrasound scan. Although she felt chest discomfort 30 min after the procedure, she assumed the symptom to be a reaction to the acupuncture. In light of our case, we advise practitioners to select appropriate acupuncture needles for patients based on the site of insertion and counsel them regarding the appearance of symptoms such as chest pain and dyspnoea immediately after the procedure.

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薬局薬剤師を対象とした漢方薬の書籍等情報源認知度調査

前田 絢子, 湯本 哲郎, 里 香世子, 稲葉 健二郎, 小湊 英範, 木村 隆夫, 中村 智徳, 吉野 鉄大, 堀場 裕子, 渡辺 賢治 and 亀井 淳三

未病と抗老化 （(一財)博慈会老人病研究所）  30   52 - 58 2021年

ISSN  1347-667X

　概要を見る

[目的]漢方薬に興味がある薬剤師、苦手意識がある薬剤師はともに7割を超えており、西洋薬よりも服薬指導が難しいとする薬剤師が半数を超えている。薬局薬剤師の漢方薬服薬指導の質的向上を図るため、漢方薬を対象とした書籍等情報源認知度の現状を把握し、抽出された課題への解決策を検討した。[方法]保険薬局に勤務する薬剤師を対象とし、webアンケート調査を実施した。薬局に一般的に所蔵されている情報源の記載項目を参考に臨床現場で直面するシナリオを10問(西洋薬との併用、漢方薬との併用、禁忌、適応外処方、小児用量、副作用、妊婦への使用、組成・性状(構成生薬)、重要な基本的注意、副作用の好発時期)設定した。シナリオ提示後、対象者に各シナリオを解決するための情報検索方法を知っているか質問し、知っていると申告した場合は検索する情報源も質問した。対象者を認定や刻み生薬調剤経験または、漢方処方取り扱いが多い群(A群)と少ない群(B群)に分類した。項目別認知度は、質問毎に、情報検索方法を知っており、書籍等の情報源を回答した人数の有効回答数に対する割合とした。A群とB群で比較した。[結果]456名(A群:141名、B群:315名)より解答が得られた。項目別認知度は全体で35-70%であった。西洋薬との併用、漢方薬との併用(P<0.01)、適応外処方、副作用、組成・性状(構成生薬)、小児用量、禁忌(P<0.05)で、B群の項目別認知度の方がA群より有意に低かった。[考察]漢方薬の項目別認知度は、今後改善の余地があると考える。大学における漢方薬の情報源及び記載内容の知識を向上させる教育の拡充、生涯学習を通した薬局薬剤師の能力の改善が未病社会における漢方薬の適正使用のために必要であると考える。(著者抄録)

甘草の副作用、偽アルドステロン症の発症メカニズムとその予防

吉野鉄大

（ シンポジウム 15「生薬・漢方薬の医薬品情報最前線」 ）  2021年

しくじり先生　俺みたいになるな

吉野鉄大

2021年

漢方薬の選びかた風邪＆インフルエンザ そしてCOVID-19/POST COVID-19

吉野鉄大

2021年

漢方製剤の処方選択支援モデルの開発とそのビジョン

吉野鉄大

2021年

A multi-center, randomized controlled trial by the Integrative Management in Japan for Epidemic Disease (IMJEDI study-RCT) on the use of Kampo medicine, kakkonto with shosaikotokakikyosekko, in mild-To-moderate COVID-19 patients for symptomatic relief and prevention of severe stage: A structured summary of a study protocol for a randomized controlled trial

Takayama S., Namiki T., Ito T., Arita R., Nakae H., Kobayashi S., Yoshino T., Ishigami T., Tanaka K., Kainuma M., Nochioka K., Takagi A., Mimura M., Yamaguchi T., Ishii T.

Trials （Trials）  21 （ 1 ） 827 - 827 2020年10月

　概要を見る

Objectives: We aimed to test our hypothesis that additional administration of traditional Japanese (Kampo) medicine, kakkonto (kakkon-To: KT) and shosaikotokakikyosekko (sho-saiko-To-ka-kikyo-sekko: SSKKS), is more effective in relieving symptoms and preventing the onset of severe infection in mild-To-moderate COVID-19 patients compared to those treated only with conventional treatment. Trial design: The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator-sponsored, two-Arm study. Participants: Patients and inpatients will be recruited from 8 Japanese academic and non-Academic hospitals. The inclusion and exclusion criteria are as follows: Inclusion criteria: 1. Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 2. Clinical stages of mild-To-moderate COVID-19 3. Symptomatic 4. ≥ 20 years of age 5. Male or female 6. Ability to communicate in Japanese 7. Outpatients and inpatients 8. Provided informed consent Exclusion criteria: 1. Difficulty in providing informed consent due to dementia, psychosis, or psychiatric symptoms 2. Allergic to Kampo or Western medicines used in this study 3. Pregnant and lactating 4. Unable to follow up 5. Participating in another clinical trial or interventional study 6. Hypokalemic or taking oral furosemide or steroids 7. Determined unsuitable for this study by the physician Intervention and comparator: Patients in the control group will receive conventional treatment with antipyretics, painkillers, or antitussives for symptoms that occurred after they contracted the SARS-CoV-2 infection. Patients in the Kampo group will receive 2.5 g of KT (TJ-1@TSUMURA and Co.) and 2.5 g of SSKKS (TJ-109@TSUMURA and Co.) 3 times a day, orally, for 14 days in addition to the conventional treatment as mentioned above. Main outcomes: The number of days till at least one of the symptoms (fever, cough, sputum, malaise, shortness of breath) improves in the first 14 days of treatment. To assess the cough, sputum, malaise, and shortness of breath, a numeric rating scale will be used to define improvement in terms of a 2-point decrease in the number of days from the start of treatment for at least 2 days. Fever will be defined as an improvement when the temperature is less than 37 °C. Randomization: Patients are randomized (1:1 ratio) to each group using the minimization method, with balancing of the arms with severity of disease stage and patient age (< 65, 65 to < 75, or ≥ 75 years). Computer-generated random numbers will be used for the minimization method. Blinding (masking): Open-label with no blinding Numbers to be randomized (sample size): The main research hypothesis of this study is that the combination of Kampo medicine and conventional treatment will significantly improve the patients' symptoms (fever, fatigue, cough, sputum, and shortness of breath) during the first 14 days of treatment as compared with conventional treatment alone. Concerning the analysis of the primary endpoint, the duration of time before improvement of at least one of the common cold-like symptoms (fever, malaise, cough, sputum, and shortness of breath) will be estimated using the Kaplan-Meier method, and the survival curves will be compared between groups using the log-rank test. Assuming this method of analysis and based on previous studies reporting the efficacy of Kampo medicine for COVID-19 and H1N1 influenza patients, the median survival time in the Kampo medicine group is estimated as 3 days; this time will be 1.5 times longer in the control group. Assuming a one-sided significance level of 5%, a power of 70%, and an allocation ratio of 1:1, the required sample size is calculated as 126 cases. To compensate for a loss in follow-up, we plan to include 150 cases in both groups (Kampo group = 75, control group = 75). Trial status: Protocol version 1.2 as of August 20, 2020 Recruitment start (expected): October 1, 2020 Recruitment finish (expected): October 31, 2023 Trial registration: Japan Registry of Clinical Trials (jRCT) jRCTs021200020. Registered on August 25, 2020 Full protocol: The full protocol is attached as an additional file and is accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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虚実中間証を含む虚実証の予測モデル

前田 絢子, 吉野 鉄大, 片山 琴絵, 堀場 裕子, 引網 宏彰, 嶋田 豊, 並木 隆雄, 田原 英一, 南澤 潔, 村松 慎一, 山口 類, 井元 清哉, 宮野 悟, 美馬 秀樹, 三村 將, 中村 智徳, 渡辺 賢治

日本東洋医学雑誌 （(一社)日本東洋医学会）  71 （ 4 ） 315 - 325 2020年10月

ISSN  0287-4857

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[目的]自動問診システムを用いて得た患者問診結果から医師の虚実診断を予測するモデルを構築したが、既報のモデルは中間証を予測できなかった。本研究では、中間証を含む虚実予測モデルを構築し施設間でカットオフ値を比較した。[方法]2012年1月-2015年2月に6施設を初めて受診し研究に同意した患者を対象とした。データ欠損、20歳未満、問診項目回答数が20項目未満、対象でない証の患者を除外した。ランダムフォレストを用いて、6施設統合データより抽出した学習データから虚実予測モデルを構築した。[結果]施設毎に学習データを除いたデータから虚実予測値を算出した。医師の診断結果をもとに受信者動作特性曲線からカットオフ値を求めたところ、全施設の虚実予測値のカットオフ値は虚証と中間証が0.5以下、実証と中間証が0.5以上であった。[考察]虚実予測モデルより計算した全施設のカットオフ値は狭い範囲に収まっていた。(著者抄録)

漢方薬の副作用に関連した最近の研究成果から　甘草による偽アルドステロン症の新たな原因物質の可能性

中村智徳, 吉野鉄大, 堀場裕子, 渡辺賢治, 三村將, 小川恵子, 南澤潔, 並木隆雄 and 牧野利明

医薬品相互作用研究 44 （ 2 ） 75 - 86 2020年09月

ISSN  0385-5015

Discrimination of prediction models between cold-heat and deficiency-excess patterns

Maeda-Minami A., Yoshino T., Katayama K., Horiba Y., Hikiami H., Shimada Y., Namiki T., Tahara E., Minamizawa K., Muramatsu S., Yamaguchi R., Imoto S., Miyano S., Mima H., Mimura M., Nakamura T., Watanabe K.

Complementary Therapies in Medicine （Complementary Therapies in Medicine）  49   102353 - 102353 2020年03月

査読有り,  ISSN  09652299

　概要を見る

Objective: The purpose of this study was to extract important patient questionnaire items by creating random forest models for predicting pattern diagnosis considering an interaction between deficiency-excess and cold-heat patterns. Design: A multi-centre prospective observational study. Setting: Participants visiting six Kampo speciality clinics in Japan from 2012 to 2015. Main outcome measure: Deficiency–excess pattern diagnosis made by board-certified Kampo experts. Methods: We used 153 items as independent variables including, age, sex, body mass index, systolic and diastolic blood pressures, and 148 subjective symptoms recorded through a questionnaire. We sampled training data with an equal number of the different patterns from a 2 × 2 factorial combination of deficiency–excess and cold–heat patterns. We constructed the prediction models of deficiency–excess and cold–heat patterns using the random forest algorithm, extracted the top 10 essential items, and calculated the discriminant ratio using this prediction model. Results: BMI and blood pressure, and subjective symptoms of cold or heat sensations were the most important items in the prediction models of deficiency–excess pattern and of cold–heat patterns, respectively. The discriminant ratio was not inferior compared with the result ignoring the interaction between the diagnoses. Conclusions: We revised deficiency–excess and cold–heat pattern prediction models, based on balanced training sample data obtained from six Kampo speciality clinics in Japan. The revised important items for diagnosing a deficiency–excess pattern and cold–heat pattern were compatible with the definition in the 11th version of international classification of diseases.

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Prediction of Deficiency, Medium, and Excess Patterns in Japanese Kampo Medicine: A Multicenter Prospective Observational Study

Ayako Maeda-Minami, Tetsuhiro Yoshino, Yuko Horiba, Hiroaki Hikiami, Yutaka Shimada, Takao Namiki, Eiichi Tahara, Kiyoshi Minamizawa, Shinichi Muramatsu, Masaru Mimura, Tomonori Nakamura, Kenji Watanabe

2020年

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こんな人が来ている漢方外来

鉄大, 吉野

2020年

Japanese government research grants for Kampo medicine: aAn overview of 10 years (1997-2017).

Hyun MK, Yoon HY, Yoshino T, Park MJ

Integrative medicine research 8 （ 4 ） 279 - 283 2019年12月

査読有り,  ISSN  2213-4220

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Identification of glycyrrhizin metabolites in humans and of a potential biomarker of liquorice-induced pseudoaldosteronism: a multi-centre cross-sectional study

Takahashi K., Yoshino T., Maki Y., Ishiuchi K., Namiki T., Ogawa-Ochiai K., Minamizawa K., Makino T., Nakamura T., Mimura M., Watanabe K.

Archives of Toxicology （Archives of Toxicology）  93 （ 11 ） 3111 - 3119 2019年11月

査読有り,  ISSN  03405761

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Liquorice [main ingredient, glycyrrhizin (GL)] is widely used as a food sweetener and herbal medicine. Occasionally, liquorice consumption causes pseudoaldosteronism as a side effect which causes oedema, hypokalaemia, and hypertension due to hyperactivity of mineral corticoid receptor. We aimed to detect GL metabolites in human blood and urine samples and to determine the pathological relationship between GL metabolites and pseudoaldosteronism. For this multi-centre, retrospective, cross-sectional study, we recruited patients who had visited Center for Kampo Medicine in Keio University Hospital, Department of Japanese Oriental (Kampo) Medicine in Chiba University Hospital, Clinic of Japanese Oriental (Kampo) Medicine in Kanazawa University Hospital, and Department of Oriental Medicine in Kameda Medical Center from November 2011 to July 2018. We collected laboratory data including concentration of serum potassium, plasma activity of renin and aldosterone, and residual blood and/or urine samples of participants who had experienced symptoms/signs of pseudoaldosteronism in the form of increase in blood pressure and occurrence or aggregation of oedema while taking liquorice-containing herbal preparations, and measured GL metabolites using a highly selective liquid chromatography tandem mass spectrometer system. We registered 97 participants (mean age 60 ± 15 years; male:female 14:83). 18β-glycyrrhetinic acid (GA) was detected in 67 serum samples (median 122 nM, range 5 nM–1.8 µM) and 18β-glycyrrhetyl-3-O-sulfate (compound 3) in 68 samples (median 239 nM, range 2 nM–4.2 µM). 3-Monoglucuronyl 18β-glycyrrhetinic acid, 22α-hydroxy-18β-glycyrrhetyl-3-O-sulfate-30-glucuronide, 22α-hydroxy-18β-glycyrrhetyl-3-O-sulfate, and GL itself were not or rarely detected. We could not find any correlation between blood pressure or peripheral oedema and serum concentration of GL metabolites. Sulfotransferase 2A1 catalysed the metabolic reaction of GA to compound 3, a major GL metabolite in human blood. High serum concentration of compound 3 was related to lower renin, aldosterone, and potassium levels, suggesting a pathological relationship between compound 3 and liquorice-induced pseudoaldosteronism. This is the first study to identify the association between a novel metabolite, compound 3, and the incidence of pseudoaldosteronism, highlighting it as a promising biomarker.

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Differences in demographics and complementary and alternative medicine use between patients attending integrative kampo versus biomedical clinics in Japan

Melby M., Yoshino T., Tonob D., Horiba Y., Watanabe K.

Complementary Therapies in Medicine （Complementary Therapies in Medicine）  46   202 - 209 2019年10月

査読有り,  ISSN  09652299

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© 2019 Elsevier Ltd Objectives: Growing interest in integrative medicine motivates examination of who seeks integrative care, and why. By examining differences in demographics and complementary and alternative medicine (CAM) use between patients recruited from Japanese Kampo (traditional herbal medicine) versus biomedical clinics, this study aimed to identify whether integrative medicine options might attract different patients. Design and setting: In this cross-sectional, observational study we administered the International Complementary and Alternative Medicine-Questionnaire (I-CAM-Q) to 209 patients recruited from four hospital clinics. Demographics, use of different types of CAM (self-help CAM, CAM practitioners, CAM products), and motivations were compared between Kampo and Non-Kampo patients and by gender. Factors influencing attendance at the Kampo clinic and CAM use were identified using logistic regression. Results: While some demographic characteristics, CAM provider and total CAM use differed between Kampo and non-Kampo patients, self-help CAM use did not. Motivations (for acute, long-term, health maintenance, or other reasons) differed between Kampo and non-Kampo clinic patients for going to non-Kampo physicians (P = 0.02) and Kampo physicians (P = 0.1). Logistic regression results for ‘any CAM’ use showed odds ratio of 0.32 (95%CI 0.15-0.67) for self-rated health, and 1.60 (95%CI 1.10–2.32) for Macarthur subjective social status scale. Attendance at the Kampo clinic showed odds ratios of 1.50 (95%CI 1.11–2.02) for education and 0.56 (95%CI 0.39-0.80) for employment status. Conclusions: Better understanding of factors such as motivation, self-rated health, and socioeconomic conditions that influence patients’ CAM use and integrative clinic attendance may enable more effective targeting of populations and integration of CAM into biomedical settings.

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Classification of patients with cold sensation by a review of systems database: A single-centre observational study

Yoshino T., Katayama K., Yamaguchi R., Imoto S., Miyano S., Mima H., Watanabe K.

Complementary Therapies in Medicine （Complementary Therapies in Medicine）  45   7 - 13 2019年08月

査読有り,  ISSN  09652299

　概要を見る

© 2019 Elsevier Ltd Objectives: In Kampo medicine, a traditional medicine pattern(TM1) refers to the complete clinical presentation of the patient at a given moment in time. Candidate herbal formulas are chosen for a chief complaint, and an appropriate formula is determined on the basis of the pattern(TM1) diagnosis. In this study, we demonstrated the importance of accompanying symptoms in diagnosing traditional medicine patterns(TM1). Design: Single centre observational study. Setting: We analysed data from 524 new patients with a hypersensitivity to cold sensation as their primary diagnosis (mean age 51.6 ± 17.8 years; female ratio 82.1%) who visited the Keio University Hospital Kampo Clinic between 2008 and 2013. Main outcome measures: Accompanying symptoms were recorded on the browser-based e-questionnaire system, which contained 128 items. The Japan Society for Oriental Medicine's board certified Kampo specialists diagnosed the traditional medicine patterns(TM1). Results: When participants were classified according to the origin of their cold sensation, there were no differences in their traditional medicine patterns. In contrast, when patients were classified based on the number of accompanying symptoms, a significant difference in the patterns was identified. An increasing number of accompanying symptoms was associated with more frequent qi stagnation and blood stasis pattern(TM1). Patients with a qi stagnation pattern had higher rates of depression and insomnia. In contrast, patients with a blood stasis pattern(TM1), had higher rates of acne, body stiffness, and menstrual abnormality. Conclusions: Qi stagnation and blood stasis patterns(TM1) are related to a number of different accompanying symptoms in the patients with hypersensitivity to cold sensation.

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Prediction of deficiency-excess pattern in Japanese Kampo medicine: Multi-centre data collection

Maeda-Minami A., Yoshino T., Katayama K., Horiba Y., Hikiami H., Shimada Y., Namiki T., Tahara E., Minamizawa K., Muramatsu S., Yamaguchi R., Imoto S., Miyano S., Mima H., Mimura M., Nakamura T., Watanabe K.

Complementary Therapies in Medicine （Complementary Therapies in Medicine）  45   228 - 233 2019年08月

査読有り,  ISSN  09652299

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© 2019 Elsevier Ltd Objective: The purpose of the present study was to compare important patient questionnaire items by creating a random forest model for predicting deficiency-excess pattern diagnosis in six Kampo specialty clinics. Design: A multi-centre prospective observational study. Setting: Participants who visited six Kampo specialty clinics in Japan from 2012 to 2015. Main outcome measure: Deficiency-excess pattern diagnosis made by board-certified Kampo experts. Methods: To predict the deficiency-excess pattern diagnosis by Kampo experts, we used 153 items as independent variables, namely, age, sex, body mass index, systolic and diastolic blood pressures, and 148 subjective symptoms recorded through a questionnaire. We extracted the 30 most important items in each clinic's random forest model and selected items that were common among the clinics. We integrated participating clinics’ data to construct a prediction model in the same manner. We calculated the discriminant ratio using this prediction model for the total six clinics’ data and each clinic's independent data. Results: Fifteen items were commonly listed in top 30 items in each random forest model. The discriminant ratio of the total six clinics’ data was 82.3%; moreover, with the exception of one clinic, the independent discriminant ratio of each clinic was approximately 80% each. Conclusions: We identified common important items in diagnosing a deficiency-excess pattern among six Japanese Kampo clinics. We constructed the integrated prediction model of deficiency-excess pattern.

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易怒性を伴う高齢者の便秘症状に大承気湯が奏効し、治療後にアルツハイマー型認知症の合併が明らかになった2例

小池 宙, 吉野 鉄大, 中澤 敦, 堀場 裕子, 足立 智英, 渡辺 賢治

日本東洋医学雑誌 （(一社)日本東洋医学会）  70 （ 3 ） 219 - 226 2019年07月

ISSN  0287-4857

　概要を見る

[緒言]大承気湯により便秘と精神状態が改善した後、アルツハイマー型認知症が明らかとなった便秘型過敏性腸症候群の2例を報告する。[症例1]82歳男性。過敏性腸症候群に対して整腸剤や下剤で治療を受けるも改善せず精神状態も不安定だった。大承気湯を開始後、消化器症状は精神状態とともに安定した。その後の検査でアルツハイマー型認知症が明らかになった。[症例2]74歳男性。強い便秘症状があり浣腸と摘便を時に怒りを表出しながら強く希望し受診していた。大承気湯開始後、便秘は改善し精神状態も安定した。その後アルツハイマー型認知症が明らかとなった。[考察]易怒性を伴う便秘に大承気湯が有効だった2例を経験した。自覚なく未診断だったアルツハイマー型認知症が背景に存在し、そのストレスが便秘型過敏性腸症候群の増悪因子だったと考えられた。易怒性を伴う便秘患者には認知症が隠れている可能性があり注意する必要がある。(著者抄録)

Risk factors associated with pseudoaldosteronism in patients with chronic hepatitis: A retrospective cohort study

Komatsu A., Yoshino T., Suzuki T., Nakamura T., Kanai T., Watanabe K.

Basic and Clinical Pharmacology and Toxicology （Basic and Clinical Pharmacology and Toxicology）  124 （ 5 ） 607 - 614 2019年05月

査読有り,  ISSN  17427835

　概要を見る

© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society) Glycyrrhizin is used to treat chronic hepatitis, but it also plays an important role in pseudoaldosteronism. Multidrug resistance-associated protein 2 is important for glycyrrhizin excretion. Dysfunction of this transporter increases the serum levels of direct bilirubin, glycyrrhizin and its metabolites. Hence, elevated direct-bilirubin levels could predict the risk of pseudoaldosteronism. This study aimed to evaluate the relationship between elevated direct-bilirubin levels and hypokalaemia, which is the most sensitive marker of pseudoaldosteronism. This retrospective cohort study was conducted in a Japanese university hospital. The occurrence of hypokalaemia is defined as a serum potassium level of ≤3.5 mEq/L after the administration of a glycyrrhizin-containing medication, and a further decline of ≥0.5 mEq/L or an increase of ≥0.5 mEq/L after discontinuing the glycyrrhizin-containing medication was examined in patients with chronic hepatitis between January 2009 and December 2015. This analysis involved 1392 patients, including 596 women. Hepatitis C virus infections were the most common cause of chronic hepatitis in this study. Seventy-nine patients received glycyrrhizin (exposed group; mean age: 60.5 ± 14.2) and 1313 did not receive glycyrrhizin (control group; mean age: 58.3 ± 15.8 years). Synergistic effects of glycyrrhizin-containing medications and elevated direct-bilirubin levels were associated with hypokalaemia. Elevated direct-bilirubin levels and hypoalbuminaemia were associated with hypokalaemia in the exposed group. Older age, female sex, high daily glycyrrhizin dosage, longer duration of glycyrrhizin intake, and potassium-lowering medications were not associated with hypokalaemia after the model adjustment. Elevated direct-bilirubin levels and hypoalbuminaemia may predict pseudoaldosteronism caused by glycyrrhizin.

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Clinical Roundup: Selected Treatment Options for Respiratory Infections

吉野 鉄大

Alternative and Complementary Therapies 25 （ 2 ） 116 - 119 2019年04月

査読有り

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The use of maoto (Ma-Huang-Tang), a traditional Japanese Kampo medicine, to alleviate flu symptoms: A systematic review and meta-analysis

Yoshino T., Arita R., Horiba Y., Watanabe K.

BMC Complementary and Alternative Medicine （BMC Complementary and Alternative Medicine）  19 （ 1 ） 68 - 68 2019年03月

査読有り

　概要を見る

© 2019 The Author(s). Background: Influenza is a common viral infection worldwide. Maoto (ma-huang-tang) was developed in ancient China and is used to alleviate flu symptoms. Currently, no meta-analyses have evaluated the efficacy and safety of maoto for alleviating flu symptoms. Methods: In the present study, we searched MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, a Japanese database (Ichushi), two Chinese databases (China National Knowledge Infrastructure and VIP), and two Korean databases (Korean Medical database and Korean Association of Medical Journal Editors) for studies published in or before October 2017. Clinical studies that compared maoto plus neuraminidase inhibitors (NAIs) vs. NAIs alone, or maoto alone vs. NAIs alone, were included in the present analysis. The primary outcome measure (efficacy) was the length of time from the start of medication to resolution of influenza symptoms (fever, headache, malaise, myalgia, and chills) and virus isolation. The secondary outcome measures (safety) were as follows: (1) side effects and adverse reactions, such as nausea, abnormal behaviour, or discontinuation of symptomatic treatment; (2) morbidity (complications caused by influenza infection) or mortality; and (3) hospitalisation for any reason. Results: Twelve relevant studies were identified, including two randomised controlled trials (RCTs, N = 60) and ten non-randomised studies (NRSs, N = 1110). We found that maoto plus NAIs was superior to NAIs alone in terms of the duration of fever in one RCT (P < 0.05, median difference = - 6 h) and four NRSs (P = 0.003, weighted mean difference = - 5.34 h). The duration of symptoms or virus isolation did not differ between maoto and NAIs. No severe side effects or adverse reactions were reported related to maoto or NAIs. Conclusions: Although we could not reach a definitive conclusion because of the small sample sizes and high risk of bias in the analysed studies, maoto may lower the duration of fever when it is used alone or in combination with NAIs and may be a well-tolerated treatment. More RCTs are needed to determine the efficacy and safety of maoto.

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証を見極め風邪の漢方を使い分ける

鉄大, 吉野

2019年

Pseudoaldosteronism as an adverse effect of Glycyrrhiza intake: pathophysiology and detection of the causative metabolite

Yoshino, Tetsuhiro

2019年

Use of maoto (Ephedra Decoction) to Alleviate Flu Symptoms

Tetsuhiro Yoshino, Ryutaro Arita, Yuko Horiba, Watanabe, Kenji

2019年

Relationship Between the Frequency of Accompanying Symptoms and Traditional Medicine Pattern Diagnosis

Yoshino, Tetsuhiro

2019年

臨床研究論文の読み方

吉野鉄大

2019年

不定愁訴に使える漢方

鉄大, 吉野

2019年

Ninjin’yoeito for cancer treatment: A systematic review

Yuko Horiba, Rie Yoshinaga, Tetsuhiro Yoshino, Kenji Watanabe

2019年

臨床医から見た国産黄連

渡辺賢治 and 吉野鉄大

（日本漢方生薬ソムリエ協会）  2019年

漢方処方の使い分けは弁証なしで統計学的に再現できるのか

吉野鉄大

日本中医学会雑誌 8 （ 1 ） 27 - 34 2018年

ISSN  2185-8713

Maoto, Traditional Kampo Formula, for Influenza: A Systematic Review and Meta-analysis

Yoshino, Tetsuhiro

2018年

臨床研究論文の読み方

吉野鉄大

2018年

かぜに対する漢方薬　〜葛根湯と麻黄湯の先に〜

吉野鉄大

2018年

キクバオウレンとセリバオウレンのアルカロイド組成比に関する検討

佐々木陽平，鈴木龍一郎，白瀧義明, 荒砥はるか，北村雅史，安藤広和，

  2P - 58 2018年

婦人科がんに対する人参養栄湯の使用実態調査

吉永瑛里, 堀場裕子, 吉野鉄大, 中村智徳 and 渡辺賢治.

2018年

　概要を見る

【目的】人参養栄湯は、がん患者や高齢者への効果を期待した研究が多く、特に婦人科がん患者の抗がん剤治療による骨髄抑制の軽減効果を検討した研究が多い。今回我々は、実臨床における人参養栄湯の使用実態を明らかにするために、当院における婦人科がん患者を中心とした人参養栄湯の使用について調査した。

Goshajinkigan for Low Back Pain: An Observational Study

Takuya Hamaguchi, Tetsuhiro Yoshino, Yuko Horiba, Kenji Watanabe

JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE 23 （ 3 ） 208 - 213 2017年03月

査読有り,  ISSN  1075-5535

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直接ビリルビン高値は偽アルドステロン症の発症を予測できるか　後ろ向き観察研究

吉野鉄大, 佐野恵, 中村はるか, 鈴木健, 中村智徳, 金井隆典 and 渡辺賢治

106 （ Suppl ） 169 2017年

偽アルドステロン症発症に関連する因子の検討－症例対象研究－

小松旺広, 吉野鉄大, 佐野恵, 中村智徳, 金井隆典 and 渡辺賢治

2017年

　概要を見る

【目的】偽アルドステロン症発症にはMultidrug Resistance Protein 2 (Mrp2)の機能低下が示唆されている。我々の先行研究ではMrp2の機能低下の指標を直接ビリルビン(D-Bil)高値、偽アルドステロン症発症の指標を低カリウム(K)血症とし、グリチルリチン(GL)含有製剤使用患者(曝露群)におけるこれらの関係性を症例対象研究で示した。今回GL含有製剤未使用患者(対照群)を対象に含め、先行研究では検証できなかった他の因子について検討を行ったので報告する。

上腕骨外側上顆炎に起因する疼痛に烏薬順気散加減が奏効した一例

濱口 卓也, 吉野 鉄大, 堀場 裕子, 吉田 祐文, 渡辺 賢治

日本東洋医学雑誌 （(一社)日本東洋医学会）  67 （ 1 ） 50 - 53 2016年01月

ISSN  0287-4857

　概要を見る

疼痛に対しては局所のお血に注目し、駆お血剤が用いられることが多い。今回、上腕骨外側上顆炎に起因する疼痛に対して、気うつに注目し、烏薬順気散加減が奏効した一例を経験したので報告する。症例は48歳女性。右肘を打撲後、疼痛が持続したため当院整形外科を受診し、上腕骨外側上顆炎と診断された。整形外科で10ヵ月間の保存療法が行われたが疼痛の改善が得られず、漢方治療を希望して当科を初診した。気分が憂鬱になる、身体が重たく感じる、月経が不順であるといった気うつに関連した症状が主で、鬱々とした話し方や表情が見られ、烏薬順気散加減の内服を開始した。1ヵ月後、首や肩の張りは消失し、痛みが軽減した。2ヵ月後、MRIで病変の改善を認めた。9ヵ月後、月経が規則的になり、11ヵ月後、痛みをほぼ感じることなく日常生活を送れるようになった。長引く疼痛で、気うつが強い症例に、烏薬順気散加減が有効である可能性が示唆された。(著者抄録)

糖尿病性末梢神経障害と漢方

吉野鉄大 and 渡辺賢治

月刊糖尿病 8 （ 8 ） 91 - 97 2016年

医学論文の読み方　臨床的疑問に医学論文をどう活用するか

吉野鉄大

2016年

不登校の孫と易疲労の祖母に柴胡加竜骨牡蛎湯が奏効した症例

沢井かおり, 吉野鉄大, 大岸美和子, 渡辺賢治 and 三村將

67 （ 別冊 ） 320 2016年

The Difference between the Two Representative Kampo Formulas for Treating Dysmenorrhea: An Observational Study.

Tetsuhiro Yoshino, Kotoe Katayama, Yuko Horiba, Kaori Munakata, Rui Yamaguchi, Seiya Imoto, Satoru Miyano, Hideki Mima, Kenji Watanabe, Masaru Mimura

Evidence-based complementary and alternative medicine : eCAM 2016   3159617 - 3159617 2016年

査読有り,  ISSN  1741-427X

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Re-finding of Shanghan-lun: A Retrospective Cross-Sectional Study

Tetsuhiro Yoshino, Tetsuya Takada, Kenji Watanabe

2016年

Predicting Japanese Kampo formulas by analyzing database of medical records: a preliminary observational study.

Tetsuhiro Yoshino, Kotoe Katayama, Yuko Horiba, Kaori Munakata, Rui Yamaguchi, Seiya Imoto, Satoru Miyano, Hideki Mima, Kenji Watanabe

BMC Med. Inf. & Decision Making 16   118 - 118 2016年

査読有り

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Effectiveness of Japanese Kampo Formulas on Dysmenorrhea: a Retrospective Observational Study.

Tetsuhiro Yoshino, Yuko Horiba, Kenji Watanabe

2016年

冷え症に対する漢方治療

吉野鉄大

2015年11月

胃切除術後難治性嘔吐を大逆上気ととらえて麦門冬湯を投与した1例

吉野 鉄大, 清水 芳政, 秋葉 哲生, 渡辺 賢治

日本東洋医学雑誌 （(一社)日本東洋医学会）  65 （ 1 ） 45 - 48 2015年

ISSN  0287-4857

　概要を見る

麦門冬湯を、咳嗽ではなく嘔吐に応用した報告は少ない。症例は84歳男性。78歳時に重複早期胃癌stage IAに対して幽門側胃切除術、ビルロートI法再建を施行された。術後に逆流感と嘔吐が持続し、制酸薬や制吐薬で改善しなかった。通過障害が疑われて80歳時に残胃空腸吻合術を施行されたが、その後も症状が持続した。再び制酸薬や六君子湯、大建中湯が試みられたが効果がなく、漢方治療目的で当外来を受診した。嘔吐は明け方に胃酸だけを吐出していた。腹部に明らかな理学所見上の異常を認めず、採血や各種画像検査でも異常を認めなかった。半夏瀉心湯、真武湯の効果は限定的だった。初診から2ヵ月後、嘔吐を大逆上気ととらえて麦門冬湯に転方したところ3週間後には嘔吐の回数が減少し、その2週間後には嘔吐がほぼ消失した。『金匱要略』の大逆上気を嘔吐と捉えることで麦門冬湯の応用範囲がひろがるのではないかと考えられた。(著者抄録)

Daisaikoto for menstrual pain: a lesson from a case with menstrual pain successfully treated with daisaikoto

Horiba, Y., Yoshino, T. and Watanabe, K.

Case Rep Med 2015   929514 2015年

査読有り,  ISSN  1687-9627

　概要を見る

Menstrual pain is one of the common symptoms among women. It is estimated that 5-14% of women are sometimes absent from school or work because of pain. Usually gynecologists prescribe analgesics and/or low-dose oral contraceptives. However, such treatment is not always effective and sometimes causes an adverse effect, such as stomach pain or low body temperature. Kampo medicine is one of the choices for the menstrual pain in Japan. Tokishakuyakusan, kamishoyosan, or keishibukuryogan is commonly used for the treatment of menstrual pain. Here we report a case of menstrual pain successfully treated with daisaikoto which is not commonly used for such a case. Twenty-five-year-old woman suffered from severe menstrual pain and stress at company. She also had constipation and abdominal distension. We prescribed daisaikoto extract 7.5 g per day. Not only menstrual pain but also constipation and abdominal distension improved within 6 months. Here we propose that daisaikoto is one of the choices for the treatment of menstrual pain with mental stress.

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月経困難症に対して頻用される当帰芍薬散と桂枝茯苓丸の使い分けを支援する統計的モデルの検証

吉野鉄大, 堀場裕子, 牧田和也, 片山琴絵, 宗形佳織, 山口類, 井元清哉, 宮野悟 and 渡辺賢治

産婦人科漢方研究のあゆみ （産婦人科漢方研究会）  04 （ 32 ） 96 - 99 2015年

研究論文（研究会，シンポジウム資料等）, 査読有り,  ISSN  0913-865X

　概要を見る

月経困難症に対する桂枝茯苓丸と当帰芍薬散の使い分けを支援する統計的モデルを,診療録を用いて新規患者に後方視的に適用した結果を報告する.対象は2013年度に月経困難症を主訴に受診した初診患者で,桂枝茯苓丸ないし当帰芍薬散が処方され,その後の経過が確認できた15例(桂枝茯苓丸12例,当帰芍薬散3例)とした.初診時の診療録の記載をもとにモデルを適用して,桂枝茯苓丸か当帰芍薬散かを予測した.診療録上の処方とモデルの予測が桂枝茯苓丸で一致した8例中5例の症状が改善し,8例のいずれにも副作用は認めなかった.診療録上の処方は桂枝茯苓丸だったが,モデルの予測で当帰芍薬散となった4例のうち,3例は症状が改善したが,2例に副作用を認めた.診療録上の処方とモデルの予測が当帰芍薬散で一致した3例は,いずれも症状が改善したが1例に副作用を認めた.結果的にわれわれのモデルによる処方選択で,副作用の頻度を減らす可能性が示唆された.(著者抄録)

Characteristics of Patients with Cancer Treated with

Hiroshi Koike, Tetsuhiro Yoshino, Yuko Horiba and Watanabe, Kenji

2015年

Visualization and Standardization of Japanese Kampo Medicine with Large Clinical Database

Tetsuhiro Yoshino, Yuko Horiba and Watanabe, Kenji

2015年

　概要を見る

Prescriptions of Kampo formulas should be administered based on traditional Kampo pattern diagnoses in order to use Kampo formulas with safe and effective results. Approximately 90% of physicians use Japanese Kampo medicine in daily practice in Japan; however, these physicians are not Kampo specialists. They hope to utilize the decision support systems to make appropriate Kampo pattern diagnoses to properly prescribe one of the 148 officially approved Kampo formulas.

Use of Kampo Medicine in University Hospital

Tetsuhiro Yoshino, Yuko Horiba and Watanabe, Kenji

2015年

　概要を見る

Kampo medicine, Japanese traditional medicine, is widely used in daily practice in Japan. We have already reported the prescription of Kampo drugs under the Japanese health care insurance program. Here, we report the current usage of Kampo drugs by physicians in one of the largest university hospital in Japan.

Mental Symptoms Can Be Treated With Japanese Kampo

Ryutaro Arita, Tetsuhiro Yoshino, Yuko Horiba and Watanabe, Kenji

2015年

Kampo treatment for low back pain in elderly patients

Takuya Hamaguchi, Tetsuhiro Yoshino, Yuko Horiba and Watanabe, Kenji

2015年

Development of Clinical Decision Support System of Japanese Kampo Medicine

Tetsuhiro Yoshino, Kotoe Katayama, Yuko Horiba, Rui Yamaguchi, Seiya Imoto, Satoru Miyano and Watanabe, Kenji

2015年

　概要を見る

Around 90% of physicians, who had studied Western medicine, used Japanese traditional Kampo medicine in daily practice. However, it is difficult for physicians who do not specialize Kampo medicine to choose proper drug from 148 Kampo p roducts which are listed on national health insurance system.

患者中心の自動問診システムを目指した課題抽出とその解決

有田, 龍太郎, 吉野, 鉄大, 片山, 琴絵, 堀場, 裕子, 宗形, 佳織, 山口, 類, 井元, 清哉, 美馬, 秀樹, 宮野, 悟 and 渡辺, 賢治

66 （ 別冊 ） 352 2015年

日常臨床に漢方薬を生かすコツ

鉄大, 吉野

2015年

方証相対的弁証の試み

吉野鉄大

2015年

Risk Factors for Pseudoaldosteronism with Rhabdomyolysis Caused by Consumption of Drugs Containing Licorice and Differences Between Incidence of These Conditions in Japan and Other Countries: Case Report and Literature Review

Yoshino, T., Yanagawa, T., Watanabe, K.

Journal of Alternaative and Complementaly Medicine 20 （ 6 ） 516 - 20 2014年03月

査読有り,  ISSN  1557-7708

　概要を見る

Abstract Background: The pathogenesis of licorice-induced pseudoaldosteronism is thought to involve the inhibition of 11beta-hydroxysteroid dehydrogenase type 2 by glycyrrhetinic acid. Some risk factors have been reported, but differences between Japan and other countries have not been reported. Case Presentation: A 79-year-old woman was hospitalized because of pseudoaldosteronism with rhabdomyolysis caused by ingestion of herbal medicines containing licorice. She had been prescribed shakuyakukanzobushito (decocted, 3 g of licorice) and keishikajutsubuto (decocted, 2 g of licorice) for the treatment of lower back pain and had been taking antihypertensive agents for the treatment of essential hypertension. After taking the herbal medicines for 2 weeks, the patient developed weakness of the extremities and pain in both thighs. On admission, she had hypertension, oliguria, an elevated serum creatine kinase level, hypokalemia, alkalemia associated with metabolic alkalosis, low plasma renin activity, and low plasma aldosterone levels. Intravenous and oral potassium supplementation and the administration of spironolactone resulted in the normalization of her condition within approximately 2 weeks. Discussion: An analysis of case reports of pseudoaldosteronism with rhabdomyolysis revealed that in Japan, most cases occurred in elderly women with essential hypertension and were caused by drugs such as herbal medicines. In contrast, in other countries, many cases involved younger men, and the dominant causes were foods containing licorice. The use of herbal medicines is increasing all over the world, and when a patient with risk factors is prescribed an herbal medicine containing licorice, careful follow-up is required.

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当院漢方医学センター外来の月経困難症患者の特徴と頻用処方予測モデルの提案

吉野鉄大, 堀場裕子, 牧田和也, 片山琴絵, 宗形佳織, 山口, 類, 井元, 清哉, 宮野, 悟 and 渡辺, 賢治

産婦人科漢方研究のあゆみ （産婦人科漢方研究会）  04 （ 31 ） 80 - 84 2014年

研究論文（研究会，シンポジウム資料等）,  ISSN  0913-865X

　概要を見る

2008年5月～2013年3月の間に漢方医学センター外来受診の女性初診患者で現在月経がある1142例を対象に、これらを月経困難症と診断された患者(D群)と月経困難症ではない患者(ND群)の2群に分け、月経困難症の特徴と漢方の処方状況について検討した。その結果、1)D群は238例(平均年齢33.7±1.0歳)、ND群は904例(35.6±0.6歳)で、両群間には年齢以外に有意差は認められなかったが、子宮内膜症の合併はD群が8.0%、ND群が3.3%にみられた。2)症状ではND群に比べD群では「月経痛」「膝の痛み」が有意に高値であるも、「ものを忘れる」「分娩」「経血量が少ない」「げっぷ」ほか、「手のしびれ」「胸痛」「足に力が入らない」は有意に低値であった。3)漢方医学的診断ではND群に比べD群で「寒証」「お血」「水毒」が有意に多い一方、「気虚」「血虚」が有意に少なかった。4)処方の解析では59.2%の患者で漢方薬が併用され、その頻度は当帰芍薬散(33.6%)、桂枝茯苓丸(29.0%)、加味逍遙散11.3%、五苓散・抑肝散の順で、鎮痛目的で投与される安中散は8.0%で、芍薬甘草湯は1.7%で処方されていた。桂枝茯苓丸と当帰芍薬散のいずれかを処方された患者の漢方診断では「やや実証」「実証」「錯雑証」「お血」が桂枝茯苓丸の処方患者で有意に多く、「やや虚証」「虚証」「寒証」「水毒」が当帰芍薬散の処方患者で有意に多かった。

当院健康維持外来における慢性頭痛に対する呉茱萸湯の検討

堀場裕子, 吉野鉄大, 牧田和也, 横田, めぐみ, 岩田, 卓, 青木, 大輔 and 吉村, 泰典

産婦人科漢方研究のあゆみ （産婦人科漢方研究会）  04 （ 31 ） 89 - 93 2014年

研究論文（研究会，シンポジウム資料等）,  ISSN  0913-865X

　概要を見る

2000年4月～2012年12月に健康維持外来受診した初診患者で、頭痛に対して呉茱萸湯エキス製剤が処方された有経・閉経68例を抽出し、これらのうち初診時の症状に対する問診票への記載が確認できた40例の回答状況の相違について検討した。その結果、1)40例中、有効は32例、無効は8例であった。また、片頭痛と診断されたのは有効例では12例、無効例では1例であり、両群間の平均年齢・BMI・閉経例の割合は有意差は認められなかった。2)問診票の項目で有意差が認められた項目は「動悸」「意欲がわかない」「腟の痒み」であった。3)呉茱萸湯の投与目標としての「頭痛」「嘔気」「手足の冷え」「肩こり」は有効例と無効例においてどちらも有意差は認められなかった。4)重症度別で比較すると「動悸」は有効例では重症度2と3が合計37%であったのに対し、無効例では重症度2と3は認められなかった。一方、「意欲がわかない」は有効例では症状ありが70%であったのに対し、無効例では47%であった。更に「腟の痒み」は有効例では症状なしと重症度1しか認めず、無効例では重症度2が25%であった。以上より、「動悸」「意欲がわかない」は呉茱萸湯の奏功例を見分ける指標となり得ることが示唆された。

月経困難症に大柴胡湯単独で奏効した2例

堀場, 裕子, 吉野, 鉄大 and 渡辺, 賢治

日本東洋医学雑誌 （(一社)日本東洋医学会）  65 （ 4 ） 298 - 301 2014年

ISSN  0287-4857

　概要を見る

月経困難症の漢方治療では、駆お血剤が処方されることが多く、大柴胡湯が第一選択になることは少ない。今回、月経困難症に大柴胡湯単独で奏効した2例を報告する。症例1は19歳、大学入学後から月経痛が悪化し、市販の鎮痛剤が無効であり、頭痛や嘔吐のため講義に出席できないこともあった。腹力充実、腹部膨満、胸脇苦満、左右臍傍の圧痛を認め、実証、熱証、気うつ証・お血証とした。大柴胡湯エキス内服4週後には月経前の頭痛や嘔気が軽減し、20週後には月経痛に対する鎮痛剤が不要となった。症例2は35歳、息子の進学問題と転居を契機に月経痛や頭痛、いらいらが出現した。腹力やや充実、腹部膨満、胸脇苦満、心下痞硬、左右臍傍の圧痛を認め、実証、熱証、気うつ証・お血証とした。大柴胡湯エキス内服8週後には頭痛やイライラが消失し、20週後には月経痛は気にならなくなった。2例とも大柴胡湯にて「気うつ」が消失し、月経痛が改善した。(著者抄録)

Kampo Traditional Pattern Diagnosis and the Clustering Analysis of Patients with Cold Sensation

Yoshino, Tetsuhiro, Katayama, Kotoe, Munakata, Kaori, Horiba, Yuko, Yamaguchi, Rui, Imoto, Seiya, Miyano, Satoru, Watanabe, Kenji

（Mary Ann Liebert, Inc., publishers）  20 （ 5 ） A47 - A47 2014年

研究論文（国際会議プロシーディングス）, 査読有り

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Kampo Traditional Pattern Diagnosis and the Clustering Analysis of Patients with Insomnia

Yuko, Horiba, Tetsuhiro, Yoshino, Kenji, Watanabe

（Mary Ann Liebert, Inc., publishers）  20 （ 5 ） A47 - A47 2014年

研究論文（国際会議プロシーディングス）, 査読有り

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Kampo Extract of Shinbuto Improved Refractory Diarrhea in Milroy's Disease 汉方真武汤提取物 - 缓解米洛病引起的顽固性腹泻

Yuko Horiba, Tetsuhiro Yoshino and Kenji Watanabe

Global Advances in Health and Medicine 2 （ 1 ） 14 - 17 2013年02月

研究論文（学術雑誌）, 共著, 査読有り

Kampo Extract of Shinbuto Improved Refractory Diarrhea in Milroy's Disease.

Horiba Y, Yoshino T, Watanabe K, Global advances in health, medicine, improving healthcare outcomes worldwide, v

2 （ 1 ） 14 - 17 2013年01月

査読有り

　概要を見る

Horiba Y, Yoshino T, Watanabe K, Global advances in health and medicine : improving healthcare outcomes worldwide, 2013, vol. 2, no. 1, pp. 14-17

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慢性膵炎による膵外分泌機能不全に投与したパンクレリパーゼが有効と考えられた1例

吉野鉄大, 竹内哲, 新井潤, 鈴木考治, 陶経緯 and 鈴木英雄

消化と吸収 （(NPO)日本消化吸収学会）  35 （ 3 ） 309 - 312 2013年

ISSN  0389-3626

　概要を見る

パンクリレパーゼは日本初の高力価パンクレアチン製剤であり、膵外分泌機能不全に対して現段階で唯一適応を持つ薬剤である。症例は78歳男性。下痢、6ヵ月後より貧血、血圧低下によるふらつき、転倒が出現し、さらに全身の浮腫と胸腹水を認めるようになり、利尿薬が開始された。膵萎縮とびまん性の石灰化、BT-PABA試験で膵外分泌能の低下(6時間値33%)が確認されたため慢性膵炎による膵外分泌機能不全と診断された。成分栄養剤と既存の消化酵素配合剤では浮腫、低蛋白血症の改善は限定的であったが、高力価消化酵素剤であるパンクレリパーゼ1,800mg/日を投与したところ、4週間後には下痢、低蛋白血症、貧血、浮腫の改善を認め、利尿薬も漸減、終了することができた。耐糖能異常を含め明らかな副作用を認めなかった。現在もパンクレリパーゼの内服を継続しており、症状の再発を認めていない。(著者抄録)

続発性無月経に烏薬順気散が有効だった一例

吉野 鉄大, 堀場 裕子 and 渡辺 賢治

日本東洋医学雑誌 （(一社)日本東洋医学会）  64 （ 4 ） 227 - 230 2013年

ISSN  0287-4857

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症例は37歳の女性。半年前のオステオパシー施術後からの無月経を主訴に当院漢方クリニックを受診した。首から腰にかけての背部痛、頸椎・肩・手・膝・足関節のクリック、筋肉のこわばりを伴ったが、日常生活は送れていた。発病前の月経周期には異常なく、産婦人科、整形外科では異常所見を認めなかった。中間証、寒証で疼痛に伴う気うつによる症状と捉え、烏薬順気散料去白姜蚕加附子(煎じ)を開始した。1ヵ月後に関節症状や冷えが軽快し、3ヵ月後に月経が再開した。烏薬順気散の原典にある婦人血風は、古典の記載から無月経と解釈しうる。漢方医学において、無月経に対する気うつの関与が指摘されてはいるが、一般的には血の症状と考えられ、補血薬や駆お血薬を用いることが多い。続発性無月経の病態には血の異常だけでなく、気の異常が密接に関係しており、気剤も治療の重要な選択肢となりうることが再確認された。(著者抄録)

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経腟採卵後の下腹部痛・発熱・頻尿、尿失禁に漢方治療が奏効した一例

吉野 鉄大, 堀場 裕子, 水口 雄貴, 佐藤 卓, 末岡 浩 and 渡辺 賢治

日本東洋医学雑誌 （(一社)日本東洋医学会）  64 （ 3 ） 173 - 176 2013年

ISSN  0287-4857

　概要を見る

経腟採卵後の著明な膀胱血腫に対して血腫除去を行った後の、日単位での変化に対する随証治療で改善をみた急性疾患の1例を報告する。症例は44歳女性。朝、体外受精のために静脈麻酔下に経腟超音波下採卵を施行し昼過ぎに帰宅した。同日夕方に、右下腹部痛、血尿、頻尿、尿失禁、発熱、悪寒が出現したため救急外来を受診し、超音波で膀胱内に径45mm程度の血腫を認めたため入院となった。膀胱洗浄後に膀胱内持続還流、抗菌薬、止血薬を投与した。右下腹部痛は持続し、第5病日に発熱が再発した。浮脈、腹力中等度、右下腹部痛、頻尿、尿失禁、便秘傾向から大黄牡丹皮湯エキスを投与し、歯痕と入院時からの下腿浮腫を水毒とし五苓散料エキスを併用した。第6病日、右下腹部痛はほぼ消失、頻尿、尿失禁は軽減し、軟便になった。発熱時の発汗、脈浮虚、腹力虚より桂枝湯エキスに転方し、軽度の頻尿、尿失禁より猪苓湯エキスを併用すると汗が持続的に出て発熱を認めなくなり、頻尿、尿失禁も消失した。第7病日、全身状態良好となったため退院となった。(著者抄録)

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Statistical analysis of hie (cold sensation) and hiesho (cold disorder) in kampo clinic

Yoshino, T., Katayama, K., Munakata, K., Horiba, Y., Yamaguchi, R., Imoto, S., Miyano, S. and Watanabe, K.

Evid Based Complement Alternat Med 2013   398458 - 398458 2013年

査読有り,  ISSN  1741-427X

　概要を見る

A cold sensation (hie) is common in Japanese women and is an important treatment target in Kampo medicine. Physicians diagnose patients as having hiesho (cold disorder) when hie disturbs their daily activity. However, differences between hie and hiesho in men and women are not well described. Hie can be of three types depending on body part where patients feel hie. We aimed to clarify the characteristics of patients with hie and hiesho by analyzing data from new patients seen at the Kampo Clinic at Keio University Hospital between 2008 and 2013. We collected information about patients' subjective symptoms and their severity using visual analogue scales. Of 4,016 new patients, 2,344 complained about hie and 524 of those were diagnosed with hiesho. Hie was most common in legs/feet and combined with hands or lower back, rather than the whole body. Almost 30% of patients with hie felt upper body heat symptoms like hot flushes. Cold sensation was stronger in hiesho than non-hiesho patients. Patients with hie had more complaints. Men with hiesho had the same distribution of hie and had symptoms similar to women. The results of our study may increase awareness of hiesho and help doctors treat hie and other symptoms.

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A Report of 2 Cases of Disseminated Invasive Aspergillosis with Myocarditis in Immunocompromised Patients

T. Yoshino, H. Nishida, T. Takita, M. Nemoto, M. Sakauchi, M. Hatano, K. Koyama, M. Hori, K. Obara

Open Journal of Pathology 3 （ 4 ） 166 - 169 2013年

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Prescription of kampo drugs in the Japanese health care insurance program

Katayama, K., Yoshino, T., Munakata, K., Yamaguchi, R., Imoto, S., Miyano, S. and Watanabe, K.

Evid Based Complement Alternat Med 2013   576973 - 576973 2013年

査読有り,  ISSN  1741-427X

　概要を見る

Kampo medicine or traditional Japanese medicine has been used under Japan's National Health Insurance scheme for 46 years. Recent research has shown that more than 80% of physicians use Kampo in daily practice. However, the use of Kampo from the patient perspective has received scant attention. To assess the current use of Kampo drugs in the National Health Insurance Program, we analysed a total of 67,113,579 health care claim records, which had been collected by Japan's Ministry of Health, Labour and Welfare in 2009. We found that Kampo drugs were prescribed for 1.34% of all patients. Among these, 92.2% simultaneously received biomedical drugs. Shakuyakukanzoto was the most frequently prescribed Kampo drug. The usage of frequently prescribed Kampo drugs differed between the youth and the elderly, males and females, and inpatients and outpatients. Kampo medicine has been employed in a wide variety of conditions, but the prescription rate was highest for disorders associated with pregnancy, childbirth, and the puerperium (4.08%). Although the adoption of Kampo medicine by physicians is large in a variety of diseases, the prescription rate of Kampo drugs is very limited.

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胃切除術後難治性嘔吐に麦門冬湯が有効と考えられた1例

吉野鉄大, 清水芳政 and 渡辺賢治

2013年

　概要を見る

緒言：麦門冬湯は一般に咳嗽に対する処方として使用される漢方薬であり、その効果や作用機序も解明されてきている。今回我々は胃切除術後の難治性嘔吐に麦門冬湯が有効と考えられた1例を経験したので報告する。

冷えを訴える患者の問診によるクラスター解析

吉野 鉄大, 片山 琴絵, 宗形 佳織, 堀場 裕子, 山口 類, 井元 清哉, 宮野 悟 and 渡辺 賢治

2013年

Data Mining Analysis as an Individualized Clinical Evidence of Kampo Medicine

Yoshino, Tetsuhiro

2013年

当院における冷え症患者と漢方処方に関する解析

吉野 鉄大, 片山 琴絵, 宗形 佳織, 堀場 裕子, 山口 類, 井元 清哉, 宮野 悟 and 渡辺 賢治

2013年

当院漢方医学センター外来における月経困難症に対する漢方薬の投薬状況についての検討

吉野鉄大, 片山琴絵, 宗形佳織, 堀場裕子, 山口類, 井元清哉, 宮野悟 and 渡辺賢治

2013年

　概要を見る

目的：当院漢方医学センターでは、患者の年齢・性別、問診情報、医師の診察結果と漢方処方のデータベースを作成し、解析を進めている。今回、月経困難症患者の特徴と漢方処方の状況を明らかにし、漢方を専門としない医師が月経困難症患者に対して漢方薬を処方するための支援情報を得ることを目的として解析を行った。

A case of hypoglycemic hemiparesis and literature review

Yoshino, T, Meguro, S, Soeda, Y, Itoh, A, Kawai, T, Itoh, H

Ups J Med Sci 117 （ 3 ） 347 - 351 2012年01月

査読有り,  ISSN  2000-1967

　概要を見る

Abstract An 89-year-old man with diabetes treated with metformin 500 mg/day and glimepiride 4 mg/day was hospitalized because of hypoglycemic right hemiparesis and dysarthria (casual glucose value 1.8 mmol/L), which resolved quickly following administration of 40 mL of 40% dextrose. Hemiparesis is a rare symptom (4.2%) of hypoglycemia. There are about 200 case reports of hypoglycemic hemiparesis. The average glucose level at which hemiparesis developed was 1.8 mmol/L. Right-sided hemiparesis predominated (R 66%; L 34%). On imaging studies, abnormal findings were frequently observed in the internal capsule or splenium of the corpus callosum. The mechanism of hemiparesis is not fully understood. The existence of cases in which hypoglycemia cannot be distinguished from stroke on imaging studies suggests the importance of measurement of the blood glucose level when the symptoms of stroke are first recognized.

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フルルビプロフェンアキセチル脂肪乳剤の反復投与中に発症したMalassezia furfur真菌血症の1例

吉野鉄大, 鈴木考治, 竹内哲, 新井潤, 山口啓二, 大平雅之, 小山和幸 and 小原克之

日本内科学会雑誌 （(一社)日本内科学会）  101 （ 11 ） 3226 - 3228 2012年

ISSN  0021-5384

　概要を見る

20歳男。14歳時に潰瘍性大腸炎と診断され、PSL、メサラジンを内服中に脳静脈洞血栓症を発症した。潰瘍性大腸炎は悪化しインフリキシマブの導入、白血球除去療法を行いコントロールされていたが、カンジダ口内炎、帯状疱疹、肛門周囲膿瘍などの感染症を繰り返した。禁食継続の上、中心静脈カテーテルからの高カロリー輸液投与とした。肛門周囲膿瘍切開、排膿後の疼痛に対し、フルルビプロフェンアキセチル脂肪乳剤(FA)の頓用を継続したが、第135病日に表皮ブドウ球菌によるカテーテル関連血流感染症を発症した。バンコマイシン投与およびカテーテル交換を行ったが、第149病日に再び発熱を認め、カテーテル抜去したところ、翌日には解熱した。カテーテル逆血培養、抜去したカテーテルの先端のいずれからも酵母様真菌が検出されたため、カンジダ血症と暫定診断し、ミカファンギンを開始し、網膜症、肝膿瘍、脾膿瘍のないことを確認した。PCRの結果から、Malassezia furfurと同定され、同菌によるカテーテル関連血流感染症と診断した。食事開始でFAを中止し以後再発は認めていない。

Usage and attitudes of physicians in Japan concerning traditional Japanese medicine (kampo medicine): a descriptive evaluation of a representative questionnaire-based survey

Moschik, E. C., Mercado, C., Yoshino, T., Matsuura, K. and Watanabe, K.

Evid Based Complement Alternat Med 2012   139818 2012年

査読有り,  ISSN  1741-4288

　概要を見る

Kampo medicine has been the primary medical model in Japan until the mid 1800s, regained a prominent role in today's Japanese medical system. Today, 148 herbal Kampo formulas can be prescribed under the national health insurance system, allowing physicians to integrate Kampo in their daily practice. This article aims to provide information about the extent to which Kampo is now used in clinics throughout Japan and about physician's current attitudes toward Kampo. We used the results of a 2008 survey that was administered to physicians throughout Japan (n = 684). The data showed that 83.5% of physicians currently use Kampo in the clinic, although the distribution of physicians who use Kampo differ widely depending on the specialty and provided a breakdown of Kampo usage by specialty. It will be interesting to see how each specialty incorporates Kampo into its respective field as Kampo continues to play a pertinent role in Japanese medical system.

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結核性リンパ節炎に対して抗結核薬投与中に出現した全身倦怠感、食欲不振に対して十全大補湯を投与した一例

吉野鉄大, 滝田節 and 渡辺賢治

2012年

潰瘍性大腸炎の経過中に脳静脈洞血栓症を発症し、入院中 潰瘍性大腸炎の再燃や感染症を繰り返した1 例

吉野鉄大, 鈴木考治, 山口啓二 and 小原克之

2012年

潰瘍性大腸炎の経過中に脳静脈洞血栓症を発症した一例

吉野鉄大, 鈴木孝治, 山口啓二 and 小原克之

2011年

亜急性の頭痛により発症したと考えられた潰瘍性大腸炎に合併した脳静脈洞血栓症の一例

吉野鉄大, 鈴木孝治, 山口啓二 and 小原克之

2011年

A patient with Graves' disease who survived despite developing thyroid storm and lactic acidosis

Yoshino, T, Kawano, D, Azuhata, T, Kuwana, T, Kogawa, R, Sakurai, A, Tanjoh, K, Yanagawa, T

Ups J Med Sci 115 （ 4 ） 282 - 286 2010年08月

査読有り,  ISSN  2000-1967

　概要を見る

Abstract A 56-year-old woman with Graves' disease presented with the complaints of diarrhea and palpitations. Physical examination and laboratory data revealed hypothermia and signs of mild hyperthyroidism, heart failure, hepatic dysfunction with jaundice, hypoglycemia, and lactic acidosis. The patient was diagnosed as having developed the complication of thyroid storm in the absence of marked elevation of the thyroid hormone levels, because of the potential hepatic and cardiac dysfunctions caused by heavy alcohol drinking. A year later, after successful treatment, the patient remains well without any clinical evidence of heart failure or hepatic dysfunction. Thyroid storm associated with lactic acidosis and hypothermia is a serious condition and has rarely been reported. Prompt treatment is essential even if the serum thyroid hormone levels are not markedly elevated. We present a report about this patient, as her life could eventually be saved.

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巨大卵巣腫瘍にバセドウ病と著しい肺高血圧症を呈した1例

吉野鉄大, 野崎勲, 西川健一郎, 渡邉昌紀 and 柳川達生

内科 （(株)南江堂）  105 （ 2 ） 350 - 352 2010年02月

ISSN  0022-1961

　概要を見る

64歳女。食欲低下と嘔吐、下痢、38℃台の発熱で急性胃腸炎と腹部腫瘤を近医にて指摘され、当院産婦人科での経腟超音波と腹部CTにて巨大卵巣腫瘍を認め手術目的入院した。甲状腺機能亢進症とNT-proBNP高値を認め内科に転科となった。眼瞼結膜貧血軽度、眼球突出軽度、甲状腺は右葉に母指頭大の圧痛を伴う腫瘤を認め、頸静脈の怒張は著明で二峰性に拍動し、FT4 4.19ng/dl、甲状腺受容抗体陽性よりバセドウ病と診断した。甲状腺エコーで甲状腺の血流は豊富で、心エコーでEF78%、推定右室収縮期圧82mmHg、右房の拡張と下大静脈の呼吸性変動低下を認めた。腹部CTで骨盤から腎レベルに達する巨大な嚢胞性腫瘍を認め、下大静脈、大動脈下部や右総腸骨～外腸骨動脈も圧排されていた。甲状腺機能亢進症と診断してヨウ化カリウム、thiamazoleとmetoprolol tartrate内服を開始し、甲状腺機能を正常化後に手術施行とした。FT4の減少に伴って肺高血圧も改善した。手術により摘出された卵巣腫瘍は嚢胞腺腫と診断され、術後9日目に退院した。

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極端な偏食により湿性脚気、大球性貧血、壊血病を呈した1症例

吉野鉄大, 中尾英一, 西川健一郎, 豊田丈夫 and 柳川達生

綜合臨床 （(株)永井書店）  58 （ 10 ） 2189 - 2191 2009年10月

ISSN  0371-1900

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34歳男。生活は不規則で、この2年間はカップラーメンと卵ご飯しか食べていなかった。1ヵ月前より嘔気と四肢・体幹の痛み、下腹部のつっぱり感が出現し、その後両脚の浮腫が出現して体幹、左腕に拡大してきた。当院内科で低アルブミン・カリウム血症、大球性高色素性貧血を指摘され、翌週の再診時に浮腫の増悪と動悸が出現したため緊急入院となった。腱反射は上下肢とも消失し、CK上昇、葉酸とビタミンB12欠乏に伴う大球性高色素性貧血、BNP高値、便潜血陽性を認め、胸部X線では両側胸水とCTR拡大がみられた。湿性脚気と診断し、ビタミンB1を含む輸液に加え、ビタミンB1、葉酸、ビタミンB12を経口で補給し、利尿剤も併用した。浮腫と胸水は急速に改善したが、浮腫改善に伴って下腿に無痛性の点状紫斑が多発してきた。ビタミンC欠乏による壊血症の併発を考え、ビタミンC、カルバゾクロム、トラネキサム酸内服を開始した。第7病日には貧血の改善と胸水・浮腫の消失を認め、翌々日軽快退院した。

• CiNii Research

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Tetsuhiro Yoshino 1), Shigenari Hozawa 1), Hideaki Kanamori 1), Toshiaki Kawai 2) , Masahiro Jinzaki 3), Yoshiyuki Yamagishi 1), Hajime Higuchi 1), , Tokuhiro Kimura 4), Taketo Yamada 4), Yasunori Okada 4), Toshifumi Hibi 1), Department of Gastroenterology, School of medicine, Keio University, Tokyo, Japan, Department of Radiology, School of medicine, Keio University, Tokyo, Japan, Department of Pathology and Laboratory Medicine, National Defense Medical College, Saitama, Japan and Department of Pathology, School of medicine, Keio University, Tokyo, Japan

AMERICAN JOURNAL OF GASTROENTEROLOGY 103   S326 - S326 2008年10月

査読有り,  ISSN  0002-9270

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