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Cholinergic Crisis with Normal Serum Cholinesterase Levels due to Excessive Galantamine Ingestion: A Case Report. 过量摄入金刚烷胺导致血清胆碱酯酶水平正常的胆碱能危象:病例报告。
Pub Date : 2024-04-15 Epub Date: 2024-04-01 DOI: 10.31662/jmaj.2023-0170
Ayaka Suzuki, Taku Mayahara, Tomohiro Katayama, Hiroyuki Arai, Kazuyoshi Matsuura, Kentaro Nagata, Eisaku Maruo

Galantamine is a cholinesterase inhibitor employed in Alzheimer's disease management. Cholinesterase inhibitors are associated with potential cholinergic side effects that, when severe, can result in cholinergic crises. Although crises induced by other cholinesterase inhibitors, such as distigmine and rivastigmine, have been reported, cases of galantamine-induced cholinergic crises remain undocumented. This study presents a case of cholinergic crisis triggered by galantamine overdose in an 89-year-old woman weighing 37 kg with Alzheimer's disease history, even though her serum cholinesterase levels were normal. The patient overdosed on 264 mg of galantamine, leading to rapid deterioration, marked by restlessness, tremors, sweating, diarrhea, pharyngeal gurgling, and severe hypoxia. Upon arrival at the emergency department, the patient exhibited pinpoint pupils, compromised airway, and low oxygen saturation, necessitating immediate intubation and transfer to the intensive care unit. After 72 h, the patient successfully recovered and was weaned off mechanical ventilation, maintaining normal serum cholinesterase levels. Animal studies suggest a lethal galantamine threshold of 3 to 6 mg/kg in humans. Unlike other cholinesterase inhibitors that typically reduce serum cholinesterase levels during cholinergic crises, galantamine appears to selectively inhibit acetylcholinesterase, possibly sparing butyrylcholinesterase. This selectivity may explain the normal serum cholinesterase levels.

加兰他敏是一种用于治疗阿尔茨海默病的胆碱酯酶抑制剂。胆碱酯酶抑制剂具有潜在的胆碱能副作用,严重时可导致胆碱能危象。虽然有报道称其他胆碱酯酶抑制剂(如地斯的明和利巴斯的明)会诱发危象,但加兰他敏诱发胆碱能危象的病例仍未见记载。本研究介绍了一例因过量服用加兰他敏而引发胆碱能危象的病例,患者是一名 89 岁的女性,体重 37 公斤,有阿尔茨海默病病史,但其血清胆碱酯酶水平正常。患者过量服用了 264 毫克加兰他敏,导致病情迅速恶化,表现为烦躁不安、震颤、出汗、腹泻、咽部咯血和严重缺氧。到达急诊科后,患者瞳孔呈针尖状,呼吸道受损,血氧饱和度低,必须立即插管并转入重症监护室。72 小时后,患者成功康复并脱离机械通气,血清胆碱酯酶水平保持正常。动物实验表明,加兰他敏对人体的致死阈值为 3 至 6 毫克/千克。其他胆碱酯酶抑制剂通常会在胆碱能危象期间降低血清胆碱酯酶水平,而加兰他敏则不同,它似乎选择性地抑制乙酰胆碱酯酶,而可能不抑制丁酰胆碱酯酶。这种选择性可能是血清胆碱酯酶水平正常的原因。
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引用次数: 0
Japanese General Clinical Oncologists' Knowledge and Real-world Experiences of Cancer Genomic Medicine: A Nationwide Web-based Survey Study. 日本普通临床肿瘤学家对癌症基因组医学的了解和实际经验:一项全国性网络调查研究。
Pub Date : 2024-04-15 Epub Date: 2024-03-15 DOI: 10.31662/jmaj.2023-0187
Ai Unzaki, Kazumi Takahashi, Yuko Ohnuki, Mizuho Yamazaki Suzuki, Kei Takeshita

Introduction: In Japan, insurance began covering two cancer gene panel tests in 2019. However, the availability of these tests remains limited to 247 facilities (as of October 2023). This survey-based study assessed the knowledge and recognition of cancer genomic medicine by physicians involved in cancer treatment.

Methods: Written requests for participation in a web-based questionnaire survey were sent to 14,579 affiliated general clinical oncologists certified by the Japanese Board of Cancer Therapy. The survey was conducted from July 1 to 31st, 2021. Data between physicians affiliated with cancer genome hospitals and noncancer genome hospitals and between regions of Japan were compared.

Results: In total, 2,402 valid responses were analyzed. Of the respondents, 1,296 and 1,106 were physicians working at cancer and noncancer genome hospitals, respectively. Physicians working at cancer genome hospitals showed significantly higher results for both knowledge of cancer genomic medicine and experience in cancer gene panel test performance compared with those working at noncancer genome hospitals. There were no significant regional differences in the percentage of physicians who reported having performed cancer gene panel tests.

Conclusions: The survey results suggest a disparity in the knowledge of cancer genomic medicine between physicians working at cancer genome hospitals and those working at noncancer genome hospitals; this disparity should be addressed by stakeholders. Closer collaboration between these facilities may be necessary to achieve national dissemination of cancer genomic medicine.

简介在日本,保险从 2019 年开始承保两种癌症基因面板检测。然而,这些检测仍仅限于 247 家机构提供(截至 2023 年 10 月)。这项基于调查的研究评估了参与癌症治疗的医生对癌症基因组医学的了解和认识:向 14,579 名获得日本癌症治疗委员会认证的附属普通临床肿瘤科医生发出了参与网络问卷调查的书面请求。调查时间为 2021 年 7 月 1 日至 31 日。对癌症基因组医院和非癌症基因组医院的附属医生之间以及日本各地区之间的数据进行了比较:共分析了 2,402 份有效答卷。在受访者中,分别有 1,296 名和 1,106 名在癌症基因组医院和非癌症基因组医院工作的医生。与在非癌症基因组医院工作的医生相比,在癌症基因组医院工作的医生在癌症基因组医学知识和癌症基因小组检测经验方面的成绩都明显较高。在报告进行过癌症基因组检测的医生比例方面,没有明显的地区差异:调查结果表明,在癌症基因组医院工作的医生与在非癌症基因组医院工作的医生在癌症基因组医学知识方面存在差距;利益相关者应解决这一差距。要在全国范围内推广癌症基因组医学,这些机构之间必须加强合作。
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引用次数: 0
Hypercapnia Induced by Pectus Excavatum and Cardiomegaly. 胸肌和心脏肥大引起的高碳酸血症
Pub Date : 2024-04-15 Epub Date: 2024-04-01 DOI: 10.31662/jmaj.2023-0162
Shota Shirotani, Yasuhiro Kano, Hiroyuki Tanaka
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引用次数: 0
Living-donor Lobar Lung Transplantation - Initiation and Development - Secondary Publication. 活体供体肺叶移植--启动与发展--二次出版。
Pub Date : 2024-04-15 Epub Date: 2024-02-09 DOI: 10.31662/jmaj.2023-0207
Hiroshi Date

Due to the difficulty of finding brain-dead donors, in October 1998, I performed the first living-donor lobar lung transplantation (LDLLT) for a ventilator-dependent 24-year-old female patient with bronchiectasis using lobes from her parents. The patient is still alive and in good health 25 years after the transplantation. Over time, the indications for LDLLT have expanded to include pulmonary hypertension, pulmonary fibrosis, congenital genetic diseases, pulmonary complications after stem cell transplantation, and, more recently, severe lung injury due to COVID-19 infection. In 2022, we successfully performed an ABO-incompatible LDLLT. To address size mismatches, we have developed new LDLLT techniques, such as right-to-left inverted transplantation, upper lobe-sparing transplantation, and segmental lung transplantation. Our published studies cover a range of topics, encompassing both basic and clinical research. Of particular significance is the observation that LDLLT offers immunological advantages over cadaveric lung transplantation (CLT). Having conducted 353 cases of lung transplantation, including 161 LDLLTs and 192 CLTs, our 5-year survival rates were 83% after LDLLT and 74% after CLT, surpassing the 55% 5-year survival rate reported by the International Society for Heart and Lung Transplantation. We have hosted numerous observers and research fellows from 15 countries. In addition, I have contributed to LDLLT procedures not only in Japan but also abroad. It brings me great satisfaction to think that my educational efforts may ultimately lead to saving the lives of those suffering from end-stage respiratory failure around the world.

由于很难找到脑死亡捐献者,1998 年 10 月,我为一名依赖呼吸机的 24 岁女性支气管扩张症患者实施了首例活体捐献肺叶移植手术(LDLLT),使用的是她父母的肺叶。移植 25 年后,患者仍然健在,身体状况良好。随着时间的推移,LDLLT 的适应症已扩展到肺动脉高压、肺纤维化、先天性遗传疾病、干细胞移植后的肺部并发症,以及最近的 COVID-19 感染导致的严重肺损伤。2022 年,我们成功实施了 ABO 不兼容 LDLLT。为了解决大小不匹配问题,我们开发了新的LDLLT技术,如右向左倒置移植、上叶保留移植和节段肺移植。我们已发表的研究涵盖一系列主题,包括基础研究和临床研究。尤其重要的是,我们发现 LDLLT 与尸体肺移植(CLT)相比,具有免疫学优势。我们进行了 353 例肺移植,包括 161 例 LDLLT 和 192 例 CLT,LDLLT 后的 5 年存活率为 83%,CLT 后的 5 年存活率为 74%,超过了国际心肺移植学会报告的 55% 的 5 年存活率。我们接待了来自 15 个国家的众多观察员和研究员。此外,我不仅在日本,还在国外为 LDLLT 手术做出了贡献。想到我在教育方面的努力最终可能会挽救全世界终末期呼吸衰竭患者的生命,我就感到非常满足。
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引用次数: 0
Development and Application of Technology for Neural Circuit Visualization - Secondary Publication. 神经回路可视化技术的开发与应用》--第二出版物。
Pub Date : 2024-04-15 Epub Date: 2024-04-05 DOI: 10.31662/jmaj.2024-0019
Shigeo Okabe

The dynamics of neurite extension and synaptic connections are central issues in neural circuit research. The development of technologies for labeling purified cytoskeletal proteins with fluorescent dyes and introducing them into living neurons using microinjection greatly facilitated our understanding of cytoskeletal dynamics in neuronal axons. Imaging data showed that the cytoskeleton repeatedly polymerized and depolymerized within the axon, and elongation was driven by the new cytoskeleton formed at the axon tip. This finding significantly revised previously proposed models that explained slow axonal transport. After the discovery of green fluorescent protein (GFP), its potential application to the live imaging of neurons was recognized in the 1990s, and a new method for visualizing synapses using GFP-tagged postsynaptic scaffolding molecules was established. This method revealed the continuous turnover of synapses during development, which overturned the established theory that synapses are highly stable once they are formed. Live imaging of synapses also demonstrated that the molecular composition of synapses changes rapidly, driven by the rapid replacement of synaptic molecules. Fluorescence measurement of single GFP molecules enabled estimation of the absolute number of postsynaptic molecules in a single synapse. Furthermore, in multiple mouse models of autism spectrum disorders (ASDs), enhanced synapse turnover was detected as a common circuit-level phenotype. This study provides solid experimental evidence that an increase in synapse dynamics underlies the pathophysiology in mouse models of ASDs. The introduction of fluorescence imaging in neurobiology revealed that the neuronal cytoskeleton and synaptic structure are not static but dynamic cellular components. Imaging technology is expected to further advance our understanding of the dynamic properties of neurons and neural circuits.

神经元延伸和突触连接的动力学是神经回路研究的核心问题。用荧光染料标记纯化的细胞骨架蛋白并通过显微注射将其引入活体神经元的技术的发展极大地促进了我们对神经元轴突中细胞骨架动态的了解。成像数据显示,细胞骨架在轴突内反复聚合和解聚,轴突末端形成的新细胞骨架驱动了轴突的伸长。这一发现极大地修正了之前提出的解释轴突运输缓慢的模型。20 世纪 90 年代,绿色荧光蛋白(GFP)被发现后,其在神经元活体成像中的潜在应用得到认可,并建立了一种利用 GFP 标记的突触后支架分子来观察突触的新方法。这种方法揭示了突触在发育过程中的不断更替,颠覆了突触一旦形成就高度稳定的既有理论。对突触的实时成像还表明,突触分子的快速更换推动了突触分子组成的快速变化。通过对单个 GFP 分子进行荧光测量,可以估算出单个突触中突触后分子的绝对数量。此外,在多个自闭症谱系障碍(ASD)小鼠模型中,检测到突触周转增强是一种常见的回路级表型。这项研究提供了确凿的实验证据,证明突触动态的增加是自闭症谱系障碍小鼠模型病理生理学的基础。在神经生物学中引入荧光成像技术揭示了神经元细胞骨架和突触结构不是静态的,而是动态的细胞成分。成像技术有望进一步推动我们对神经元和神经回路动态特性的了解。
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引用次数: 0
Efficacy of Mobile Telemedicine System for Digital Subtraction Angiography of Moyamoya Disease Compared with Picture Archiving and Communication System. 移动远程医疗系统与图片存档和通信系统对 Moyamoya 病数字减影血管造影术的疗效比较。
Pub Date : 2024-04-15 Epub Date: 2024-02-09 DOI: 10.31662/jmaj.2023-0129
Toshiya Osanai, Haruto Uchino, Masaki Ito, Miki Fujimura
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引用次数: 0
Addressing Information Gaps and Revising Coverage Terms and Conditions for Cancer Panel Testing. 填补信息空白,修订癌症全套检测的承保条款和条件。
Pub Date : 2024-04-15 Epub Date: 2024-04-01 DOI: 10.31662/jmaj.2024-0014
Yasuhito Nannya
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引用次数: 0
Editorial for Living-donor Lobar Lung Transplantation - Initiation and Development in Japan. 活体供体肺叶移植--日本的起步与发展》社论。
Pub Date : 2024-04-15 Epub Date: 2024-04-01 DOI: 10.31662/jmaj.2024-0024
Jun Nakajima
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引用次数: 0
Human Brain Magnetic Resonance Imaging Studies for Psychiatric Disorders: The Current Progress and Future Directions. 针对精神疾病的人脑磁共振成像研究:当前进展与未来方向》。
Pub Date : 2024-04-15 Epub Date: 2024-03-18 DOI: 10.31662/jmaj.2023-0167
Jennifer Shi, Shinsuke Koike

With the prevalence of psychiatric disorders and the limitations of the diagnostic scheme and treatment options of these disorders, magnetic resonance imaging (MRI) studies play a significant role in uncovering the pathological basis of psychiatric disorders and potentially using biological markers in clinical settings. The use of MRI in clinical research has grown over the past three decades, and current MRI research continues to provide an avenue to guide the development of diagnostic approaches and therapeutic solutions. However, the current shortcomings of MRI studies derive not only from technical limitations (i.e., the range of contrasts that MRI probes or sensors can create) but also from confounding factors in the current methodological approaches of case-control studies for psychiatric disorders. Thus, by reviewing the recent literature on MRI research on psychiatric disorders, we explain the current progress and limitations of brain MRI methodologies used to study psychiatric disorders. We consider the growing use of cross-disorder methods to identify shared and disease-specific pathological features across psychiatric disorders. In addition, we need to outline healthy developmental and aging changes of the brain and investigate the disorder difference as a deviation of the trajectory. Although these methods have provided us with new insights, the demarcation between psychiatric disorders based on a definitive set of pathologies remains limited. This challenge of disease stratification is further complicated by the presence of multiple different sets of disorder pathologies within a single disorder and the different progressive timelines of different disorders. As such, we introduce the ongoing research projects in Japan, namely, the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) and the Strategic International Brain Science Research Promotion Program (Brain/MINDS Beyond). These collaborative research initiatives across Japan use neuroimaging and travel-subject harmonization to conduct nationwide MRI studies capable of providing large-scale coherent results, which may address the current limitations of MRI psychiatric disorder research.

随着精神疾病的流行以及这些疾病诊断方案和治疗方法的局限性,磁共振成像(MRI)研究在揭示精神疾病的病理基础以及在临床环境中使用生物标记物方面发挥着重要作用。在过去的三十年中,磁共振成像在临床研究中的应用不断增加,目前的磁共振成像研究继续为诊断方法和治疗方案的开发提供指导。然而,目前核磁共振成像研究的不足之处不仅来自于技术上的限制(即核磁共振成像探头或传感器所能产生的对比范围),还来自于目前精神疾病病例对照研究方法中的干扰因素。因此,通过回顾近期有关精神疾病核磁共振成像研究的文献,我们解释了目前用于研究精神疾病的脑核磁共振成像方法的进展和局限性。我们将考虑越来越多地使用跨疾病方法来识别精神疾病的共同病理特征和疾病特异性病理特征。此外,我们还需要概述大脑的健康发育和衰老变化,并研究作为轨迹偏差的失调差异。尽管这些方法为我们提供了新的见解,但根据一组明确的病理特征来划分精神疾病仍然是有限的。由于同一疾病中存在多组不同的病理变化,而且不同疾病的进展时间表也各不相同,因此疾病分层的挑战变得更加复杂。因此,我们将介绍日本正在进行的研究项目,即 "疾病研究综合神经技术脑图谱"(Brain/MINDS)和 "国际脑科学研究战略推进计划"(Brain/MINDS Beyond)。这些日本全国范围内的合作研究计划利用神经影像学和旅行受试者的协调,在全国范围内开展核磁共振成像研究,能够提供大规模的一致性结果,从而解决目前核磁共振成像精神疾病研究的局限性。
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引用次数: 0
Translation and Validation of the Health Literacy Score-14 Questionnaire for Vietnamese Patients with Diabetes. 越南糖尿病患者健康素养评分-14问卷的翻译与验证。
Pub Date : 2024-04-15 Epub Date: 2024-04-10 DOI: 10.31662/jmaj.2023-0148
Khoa Tuan Vo, Khue Thy Nguyen, Hirohide Yokokawa, Aya Goto, Toshio Naito

Introduction: Health literacy (HL) is a crucial indicator for health promotion and diabetes care improvement, but the available measurements are mostly in English. This study aimed to translate and validate the 14-item Health Literacy Scale (HLS-14) questionnaire from English to Vietnamese for patients with diabetes in Vietnam.

Methods: We translated HLS-14 into Vietnamese in accordance with the World Health Organization guidelines and conducted a cross-sectional survey among 571 outpatients with type 2 diabetes using the HLS-14 Vietnamese version (HLS-14 VN). The reliability and validity of the tool were assessed using Cronbach's alpha, composite reliability (CR), average variance extracted (AVE), and maximum shared variance (MSV), and confirmatory analysis was conducted.

Results: Cronbach's alpha coefficients for the three subscales as in the original version were 0.931, 0.810, and 0.928 for functional HL, communicative HL, and critical HL, respectively. However, AVE for critical HL was 0.488, which improved to 0.516 after the removal of one item in the communicative HL. For all subscales in the revised 13-item version (HLS-13 VN), CR was above 0.8, AVE was above 0.5, and MSV was less than AVE. Confirmatory analysis of HLS-13 VN revealed an acceptable fit with comparative fit index of 0.983, goodness-of-fit index of 0.963, and root mean squared error of approximation of 0.058.

Conclusions: The reliability and validity of HLS-13 VN were confirmed. The tool is suitable for use in clinical settings in Vietnam to assess multidimensional HL in patients with type 2 diabetes.

导言:健康素养(HL)是促进健康和改善糖尿病护理的重要指标,但现有的测量方法大多使用英语。本研究旨在将 14 项健康素养量表(HLS-14)问卷从英语翻译成越南语,并对越南糖尿病患者进行验证:我们根据世界卫生组织的指南将 HLS-14 翻译成越南语,并使用 HLS-14 越南语版(HLS-14 VN)对 571 名门诊 2 型糖尿病患者进行了横断面调查。使用克朗巴赫α、综合信度(CR)、平均方差提取(AVE)和最大共享方差(MSV)评估了该工具的信度和效度,并进行了确认分析:原始版本中三个分量表的 Cronbach's alpha 系数分别为 0.931、0.810 和 0.928(功能性 HL、交际性 HL 和批判性 HL)。然而,临界水平的平均值为 0.488,在删除了交际水平中的一个项目后,平均值提高到了 0.516。在修订后的 13 个项目版本(HLS-13 VN)中,所有分量表的 CR 均高于 0.8,AVE 均高于 0.5,MSV 均小于 AVE。对 HLS-13 VN 的确认分析表明,其拟合度可以接受,比较拟合指数为 0.983,拟合优度指数为 0.963,近似均方根误差为 0.058:HLS-13 VN 的可靠性和有效性得到了证实。结论:HLS-13 VN 的可靠性和有效性得到了证实,该工具适合在越南临床环境中用于评估 2 型糖尿病患者的多维 HL。
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引用次数: 0
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