ミロシナーゼ ニ カンスル ケンキュウ

京都大学0048新制・論文博士農学博士乙第2570号論農博第517号新制||農||173(附属図書館)学位論文||S49||N685(農学部図書室)UT51-49-E198(主査)教授 秦 忠夫, 教授 森田 雄平, 教授 山田 秀明学位規則第5条第2項該当Kyoto UniversityDFA

Successful Treatment of Lithium-Induced Nephrogenic Diabetes Insipidus with Celecoxib: A Promising Therapeutic Option

BACKGROUND: Nephrogenic diabetic insipidus (NDI) poses a challenge in clinical management, particularly when associated with lithium ingestion. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of numerous diseases worldwide, including NDI. However, many studies have reported the diverse adverse effects of long-term use of non-selective NSAIDs. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a better drug to relieve pain and inflammation in terms of long-term safety and efficacy than non-selective NSAIDs. Nevertheless, there are few reports describing the effectiveness of celecoxib in treating NDI. CASE REPORT: We report a case of a 46-year-old woman with schizophrenia who presented with severe hypernatremia and refractory polyuria due to lithium-induced NDI. Cessation of lithium ingestion and traditional treatments, including trichlormethiazide and desmopressin, yielded minimal improvement in her hypernatremia and polyuria. Her sodium level needed to be strictly controlled with the infusion of dextrose 5% in water. Given the safety of celecoxib, we decided to initiate celecoxib as the treatment of lithium-induced NDI instead of indomethacin. Notably, the introduction of celecoxib led to a substantial and sustained amelioration of polyuria and hypernatremia without any celecoxib-associated adverse effects. Even after transfer to another hospital, stability in serum sodium levels persisted with celecoxib. CONCLUSIONS: We presented a case of lithium-induced NDI successfully treated with celecoxib, a selective COX-2 inhibitor. To the best of our knowledge, this is the first reported case of successful treatment of lithium-induced NDI with celecoxib, and suggests celecoxib is a viable therapeutic option warranting further exploration. Physicians should consider its use when faced with the challenging management of lithium-induced NDI

Pyogenic sacroiliitis caused by Salmonella schwarzengrund in a young healthy woman: a case report and literature review

BACKGROUND: Salmonella species are a leading cause of diarrheal diseases worldwide. Recent epidemiological studies have shown that Salmonella schwarzengrund (S. schwarzengrund) is highly prevalent in various regions. Herein, we report that S. schwarzengrund caused sacroiliac joint (SIJ) infection with septic shock in a young woman, although she was immunocompetent. CASE PRESENTATION: A 20-year-old woman presented with left hip pain, accompanied by vasopressor-requiring hypotension. Her imaging examinations showed fluid collection in her SIJ and a small abscess in the left iliac muscle. Later, the blood and aspiration fluid culture and genetic analysis revealed the presence of S. schwarzengrund. We diagnosed sacroiliac joint (SIJ) infection with septic shock caused by S. schwarzengrund. Her condition improved after performing several interventional radiology (IVR) procedures for SIJ abscesses and providing appropriate antibiotic treatment. Finally, she was discharged without any sequelae. Screening tests and genetic analysis about her immunodeficiency did not indicate a congenital disorder. CONCLUSION: These clinical courses indicate that S. schwarzengrund could cause the fatal SIJ infection irrespective of the host immunocompetence. Considering the recent increase in the diagnostic rate of S. schwarzengrund, this case emphasized the need to be more cautious about Salmonella species infection

Nurses' understanding of the necessity of core items recommended by the latest Utstein resuscitation registry template for in-hospital cardiac arrest: A cross-sectional study.

BACKGROUND: It is essential for nurses, who are more likely to be first responders to cardiac arrest patients in hospitals, to understand the items that should be recorded when a cardiac arrest occurs to record the event accurately. We aimed to assess Japanese nurses' understanding of the necessity of recording core items, as defined in the Utstein-style reporting template. METHODS: We conducted a cross-sectional study using an anonymous, self-administered online questionnaire survey at Kyoto University Hospital. In addition to nurses' understanding of the necessity of recording Utstein core items, we collected data on years of experience as a nurse, experiences of encountering in-hospital cardiac arrest (IHCA), and understanding and confidence in performing basic life support. RESULTS: Of 1, 202 eligible nurses, 492 participated, among whom 5.3% were aware of the Utstein-style reporting template. None of the items were considered “necessary” by all respondents. A documentation form listing the items to be recorded was requested by 86% of the respondents, and 82% reported having difficulties due to a lack of opportunities to learn how to write resuscitation documentation. CONCLUSION: We found that nurses lacked an understanding of the Utstein-style reporting template, which is critical for effective management and reporting of IHCA. Detailed and accurate documentation is crucial for improving outcomes in patients with IHCA. Effective education for nurses and development of a recording system are challenges that must be addressed in the future

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years

Development of HVJ-Liposome Mediated Gene Therapy Using HSV-Thymidine Kinase Gene for Hepatocellular Carcinoma

The suicide gene therapy for hepatocellular carcinoma (HCC) has given some promise, but the toxicity of adenovirusmediated gene delivery using the cytomegalovirus promoter (CMV) region linked to herpes simplex virus thymidine kinase gene (HSV-TK) in combination with ganciclovir (GCV) therapy was reported. In this study, to improve the technical issue of conventional gene therapy, we examined the usefulness of hemagglutinating virus of Japan (HVJ)-anionic-liposomemediated CMV-TK/GCV as an introductory target gene and development the selective application of alpha-fetoprotein (AFP) enhancer/promoter or heat shock protein (HSP) promoter for gene therapy. By the luciferase reporter gene assay, both HVJ-liposome transfection and the transcriptional activation of AFP enhancer/promoter or that of the HSP promoter by heat treatment were found to be quite effective in vivo and in vivo/in vitro models respectively. The toxicity of HVJ-anionic liposome-mediated gene therapy was smaller than that of adenovirus-driven approach as judged by histopathological examination of experimental animals\u27 liver and GPT blood test. Thus, the HVJ-liposome-mediated AFP-TK/GCV or HSPTK/ GCV technique may be a potent and useful strategy of the gene therapy of HCC

Facial trauma with life-threatening bleeding treated by andexanet alfa administration: A case report

Recently, anticoagulant reversal has become a treatment option for life-threatening bleeding, especially in intracranial hemorrhage. Although evidence of the beneficial efficacy of andexanet alfa accumulates in cases of intracranial hemorrhage, little is known about its effectiveness in head injuries without intracranial hemorrhage. We present the case of an 87-year-old man who suffered a stroke 1 year previously and had been taking apixaban since then, who was brought to the emergency department with facial trauma due to a fall. Upon arrival at the hospital, the patient was conscious, and his vital signs were normal; however, physical examination revealed epistaxis, and plain head computed tomography (CT) showed multiple facial fractures without intracranial hemorrhage. As epistaxis was challenging to control, upper airway obstruction developed. His percutaneous oxygen saturation (SpO₂) decreased rapidly, and he underwent tracheal intubation. Contrast-enhanced head CT revealed at least two extravasations, near the anterior wall of the right maxillary sinus and from the nasal canal to the nasopharynx area. However, embolization using interventional radiology was deemed difficult. Because the bleeding did not stop, we determined the bleeding was life-threatening and uncontrollable. Therefore, we infused andexanet alfa to stop the bleeding. After infusion, hemostasis was confirmed. This case suggests the effectiveness of andexanet alfa in cases of facial trauma and extracranial bleeding difficult to stop, resulting in favorable outcomes and hemostatic effects

Case report: Consecutive hyperbaric oxygen therapy for delayed post-hypoxic leukoencephalopathy resulting from CHANTER syndrome caused by opioid intoxication

Delayed post-hypoxic leukoencephalopathy (DPHL) is a poorly recognized syndrome characterized by neuropsychiatric symptoms following recovery from an acute hypoxic episode. Although most cases are related to carbon monoxide poisoning, some have been linked to excessive opioid use. Opioid intoxication has recently become known for manifesting the characteristic imaging findings involving cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome. Herein, we present a patient with severe disturbances in consciousness who was initially diagnosed with CO poisoning but was later found to have taken excessive tramadol. Magnetic resonance imaging (MRI) in the acute phase revealed abnormal intensities in the bilateral globus pallidus and the cerebellum, indicative of CHANTER syndrome. After intensive care, his level of consciousness was restored. However, around the 3rd week after hospitalization, his consciousness gradually deteriorated and he developed severe neurological symptoms. Another MRI on day 25 revealed a new diffuse white matter abnormality; DPHL was suspected. Cerebrospinal fluid collected on day 28 revealed significantly elevated myelin basic protein levels. Although it was challenging to decide on a treatment plan, hyperbaric oxygen (HBO) therapy trials were initiated on day 58; the patient's condition improved after a series of HBO sessions. MRI revealed gradual shrinkage of the white matter abnormality. A total of 63 consecutive HBO sessions were performed, leading to the successful resolution of the serious neurological symptoms. While the effectiveness of HBO therapy for DPHL remains inconclusive, especially in opioid-related cases, this patient made a remarkable recovery, likely due to the therapeutic effect of improved cerebral blood flow and oxygenation

Trend of anticoagulant therapy in elderly patients with atrial fibrillation considering risks of cerebral infarction and bleeding

The introduction of direct oral anticoagulants (DOACs) has greatly changed the use of anticoagulant therapy in patients with non-valvular atrial fibrillation (Af). Therefore, this study aimed to examine changes in the proportions of oral anticoagulant prescriptions in patients with non-valvular Af aged ≥ 65 years, taking into consideration the risk of cerebral infarction and bleeding. Anticoagulant prescriptions in outpatients aged ≥ 65 years with Af were temporally analyzed using the nationwide claims database in Japan. Trends in anticoagulant prescriptions were examined according to cerebral infarction and bleeding risk. The proportion of anticoagulant prescriptions for 12, 076 Af patients increased from 41% in 2011 to 56% in 2015. An increase in DOAC prescriptions was accompanied by an increase in the proportion of anticoagulant prescriptions in each group according to the CHA2DS2-VASc and HAS-BLED scores. The proportion of anticoagulant prescriptions for patients with a high risk of developing cerebral infarction and bleeding showed a marked increase. Trends in anticoagulant prescriptions in Af patient with a CHA2DS2-VASc score ≥ 2 and HAS-BLED scores ≥ 3 showed a marked increase in DOAC prescriptions. The widespread use of DOACs greatly changes the profile the prescription of anticoagulant therapy in patients with Af

Single-molecular real-time deep sequencing reveals the dynamics of multi-drug resistant haplotypes and structural variations in the hepatitis C virus genome

While direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have dramatically progressed, patients still suffer from treatment failures. For the radical eradication of HCV, a deeper understanding of multiple resistance-associated substitutions (RASs) at the single-clone level is essential. To understand HCV quasispecies and their dynamics during DAA treatment, we applied single-molecule real-time (SMRT) deep sequencing on sera from 12 patients with genotype-1b HCV infections with DAA treatment failures, both pre- and post-treatment. We identified >3.2 kbp sequences between NS3 and NS5A genes of 187, 539 clones in total, classifying into haplotype codes based on the linkage of seven RAS loci. The number of haplotype codes during the treatment, per sample, significantly decreased from 14.67 ± 9.12 to 6.58 ± 7.1, while the number of nonsynonymous codons on the seven RAS loci, per clone, significantly increased from 1.50 ± 0.92 to 3.64 ± 0.75. In five cases, the minority multi-drug resistant haplotypes at pre-treatment were identical to the major haplotypes at relapse. Moreover, various structural variations (SVs) were detected and their dynamics analysed. These results suggest that SMRT deep sequencing is useful for detecting minority haplotypes and SVs, and to evaluate the dynamics of viral genomes at the single-clone level