Research on the process by which parents of children with schizophrenia associate with their experience : From onset to continuing life in community

13301甲第4694号博士（保健学）金沢大学博士論文本文Full 以下に掲載：Journal of Wellness and Health Care 41(2) pp.57-67 2018. Wellness and Health Care Society. 共著者：Megumi Kawaguchi, Kazuyo Kitaok

Endometrial Cancer as a Familial Tumor: Pathology and Molecular Carcinogenesis (Review)

Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Such tumors are thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene, but many aspects of the pathology of familial endometrial cancer are unclear and no effective screening method has been established. However, the pathology of endometrial cancer with familial tumor has been progressively clarified in recent studies. At present, about 0.5% of all cases of endometrial cancers meet the clinical diagnostic criteria for HNPCC. A recent analysis of the three MMR genes (hMLH1, hMSH2 and hMSH6) revealed germline mutations in 18 of 120 cases (15.0%) of endometrial cancer with familial accumulation of cancer or double cancer, with a frameshift mutation of the hMSH6 gene being the most common. Many cases with mutation did not meet the current clinical diagnostic criteria for HNPCC, indicating that familial endometrial cancer is often not diagnosed as HNPCC. The results suggest that the hMSH6 gene mutation may be important in carcinogenesis in endometrial cancer and germline mutations of the MMR gene may be more prevalent in cases associated with familial accumulation of cancer. An international large-scale muticenter study is required to obtain further information about the pathology of endometrial cancer as a familial tumor

Chemotherapy with low-dose capecitabine as palliative treatment in a patient with metastatic breast cancer: a case report

Chemotherapeutic agents are rarely used for symptom management in patients under palliative care setting. This is because chemotherapeutic agents not only have limited efficacy in palliative treatment but are also known to exert severe adverse effects. We describe our experience with a patient with metastatic breast cancer who was successfully treated with low-dose capecitabine, without the development of any severe toxicities and with significant improvement in activities of daily living (ADL) and quality of life (QOL)

統合失調症の子をもつ親の経験：発症から地域生活継続に至るまで親はその経験といかに付き合っていったのか

This study presents the process of associating with experiences by parents of children with schizophrenia from onset to continuation of life in the community. Semi-structured interviews were conducted among 14 parents of children with schizophrenia. The results were analyzed using Kinoshitaʼs modified grounded theory approach. Based on the results, two categories and 13 concepts were extracted.　When children with schizophrenia experienced onset, their parents ʻcontinued living without consideration as hallucination/delusion.ʼ When the children were diagnosed as having schizophrenia, the parents were shocked by psychosis, and started the process of the [expectation of independence as parents.] This shock was influenced by the parentsʼ prejudice. The parents associated with their experience by ʻbelieving full recoveryʼ of children, and ʻtried every possible means to keep pace with others of the same generationʼ when children showed recovery. They also associated with their experience by ʻreprimandʼ children when children experienced recurrence. The parents repeatedly experienced these two associations and ʻwere not able to decide what to do to address hallucination/delusion.ʼ However, they were gradually able to ʻrespect their childrenʼ and ʻenjoying oneʼs own life apart from the role of a parentʼ based on the central concept of ʻfeeling relief from a family association,ʼ and entered the process of the [recognition of the recovery limits.] The parents were able to ʻaccept a life within the range of the childʼs abilityʼ by ʻaccepting the child with schizophrenia,ʼ which led to continuation of the childʼs life in the community. Associates of ʻaccepting the child with schizophreniaʼ and ʻaccepted a life within the range of the childʼs abilityʼ were influenced by ʻabandoning full recovery.ʼ 　However, parents became devoted to ʻpreparing for the future after the death of parentsʼ for the child as they grew older, and the feeling of ʻhoping for independence that they cannot abandonʼ for the child arose in the parentsʼ mind, causing conflict with ʻaccepting a life within the range of the childʼs abilityʼ in the parentsʼ mind.子が統合失調症の発症から地域での生活を継続していくまでに、その親はそれらの経験とどう付き合っていったかのプロセスを明らかにした。統合失調症の子をもつ親 14 名を対象として，半構構造化面接を実施し、木下の修正版グランデッド・セオリー・アプローチを用いて分析した。結果，2 つのカテゴリー，13 の概念を抽出した。　子の発症当時の親は、子の症状を「幻覚・妄想と捉えず生活を継続」していた。子が診断を受けることで親は精神疾患への衝撃を受け、【親としての自立への期待】のプロセスに入っていた。この衝撃には、親自身の偏見が影響していた。親は、子の「完治を信じる」ことを行い、子の回復が見られると「同世代と足並みを揃えるために手を尽くす」ことを行っていた。また、子が再発を経験すると「叱咤激励する」ことを行っていた。この二つを幾度も経験することで親は「幻覚・妄想への対応に迷走」していた。しかし、「家族会から安心を得る」ことをコアの概念として、「子を尊重する」ことや「自分の人生を楽しむ」ことができるようになり、【回復の限界の認識】のプロセスに入っていた。親は、「統合失調症の子を受容する」ことで「子のできる範囲の生活を受け入れる」ことができ、子の地域での生活継続に至っていた。「統合失調症の子を受容する」と「子のできる範囲の生活を受け入れる」ことには、「完治を諦める」ことが影響していた。その一方で，年齢を重ねるにつれ，子の「親亡き将来の準備をする」ことに力を注ぐようになり，子の「自立への捨てきれない望みを抱く」思いが沸き上がり、「子のできる範囲の生活を受け入れる」こととの間で，心の葛藤を生んでいた

Hub structure in functional network of EEG signals supporting high cognitive functions in older individuals

IntroductionMaintaining high cognitive functions is desirable for “wellbeing” in old age and is particularly relevant to a super-aging society. According to their individual cognitive functions, optimal intervention for older individuals facilitates the maintenance of cognitive functions. Cognitive function is a result of whole-brain interactions. These interactions are reflected in several measures in graph theory analysis for the topological characteristics of functional connectivity. Betweenness centrality (BC), which can identify the “hub” node, i.e., the most important node affecting whole-brain network activity, may be appropriate for capturing whole-brain interactions. During the past decade, BC has been applied to capture changes in brain networks related to cognitive deficits arising from pathological conditions. In this study, we hypothesized that the hub structure of functional networks would reflect cognitive function, even in healthy elderly individuals.MethodTo test this hypothesis, based on the BC value of the functional connectivity obtained using the phase lag index from the electroencephalogram under the eyes closed resting state, we examined the relationship between the BC value and cognitive function measured using the Five Cognitive Functions test total score.ResultsWe found a significant positive correlation of BC with cognitive functioning and a significant enhancement in the BC value of individuals with high cognitive functioning, particularly in the frontal theta network.DiscussionThe hub structure may reflect the sophisticated integration and transmission of information in whole-brain networks to support high-level cognitive function. Our findings may contribute to the development of biomarkers for assessing cognitive function, enabling optimal interventions for maintaining cognitive function in older individuals

A Proposal for Practical Diagnosis of Renal Hypouricemia : Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals

Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FEUA). Further studies on FEUA in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. Methods: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of URAT1 (NFV-URAT1), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FEUA data. The effects of NFV-URAT1 on FEUA and SUA were also investigated using linear and multiple regression analyses. Results: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV-URAT1 were observed in 1040 hypouricemic individuals. Furthermore, NFV-URAT1 significantly increased FEUA and decreased SUA, enabling FEUA and SUA levels to be estimated. Conversely, FEUA and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-URAT1. Conclusions: Our findings reveal that specific patterns of FEUA and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests

A Cluster of Respiratory Syncytial Virus Infections in a Hospital Ward for Adult Immunocompromised Patients

Four male patients admitted to the same ward in the first half of September 201Y were identified to have respiratory syncytial virus（RSV）infection. Their ages ranged from 49 to 85 years（median 72.5）. One patient was infected with human immunodeficiency virus and three patients had hematological malignancies. Following immuno-chromatological testing with a nasal cavity swab, RSV infection was diagnosed. Although blood and sputum cultures were performed in three patients, no significant bacteria were detected. Two cases responded to supportive therapy. However, one patient died secondary to multiple myeloma, and another patient developed pneumonia and died with an exacerbation of leukemia. RSV infections in immunocompromised hosts are associated with a poor prognosis. Early diagnosis will facilitate isolation of infected individuals to prevent hospital outbreaks

Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout

Objective The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout. Methods We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia). Results This new approach enabled us to identify two novel gout loci (rs7927466 of CNTN5 and rs9952962 of MIR302F) and one suggestive locus (rs12980365 of ZNF724) at the genome-wide significance level (p<5.0×10– 8). The present study also identified the loci of ABCG2, ALDH2 and SLC2A9. One of them, rs671 of ALDH2, was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three ‘gout vs AHUA GWAS’-specific loci (CNTN5, MIR302F and ZNF724) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level. Conclusions This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals

Literature survey on epidemiology and pathology of gangliocytic paraganglioma

<p>Abstract</p> <p>Background</p> <p>Although gangliocytic paraganglioma (GP) has generally been regarded as a neuroendocrine tumor, its origin remains unclear. We therefore aimed to investigate the details of this disease by carefully analyzing and extracting common features of the disease as presented in selected publications.</p> <p>Methods</p> <p>We searched for English and Japanese cases of GP using the PubMed and IgakuChuoZasshi databases on August 2010. We then extracted and sampled raw data from the selected publications and performed appropriate statistical analyses. Additionally, we evaluated the expression of hormone receptors based on our previously reported case.</p> <p>Results</p> <p>192 patients with GP were retrieved from the databases. Patient ages ranged from 15 y to 84 y (mean: 52.3 y). The gender ratio was 114:76 (male to female, 2 not reported). Maximum diameter of the tumors ranged from 5.5 mm to 100 mm (mean: 25.0 mm). The duodenum (90.1%, 173/192) was found to be the most common site of the disease. In 173 patients with duodenal GP, gastrointestinal bleeding (45.1%, 78/173) was found to be the most common symptom of the disease, followed by abdominal pain (42.8%, 74/173), and anemia (14.5%, 25/173). Rate of lymph node metastasis was 6.9% (12/173). Our statistical analysis indicated that significant differences were found for gender between GP within the submucosal layer and exceeding the submucosal layer. Furthermore, our immunohistochemical evaluation showed that both epithelioid and pancreatic islet cells showed positive reactivity for progesterone receptors.</p> <p>Conclusions</p> <p>Our literature survey revealed that there were many more cases of GP exceeding the submucosal layer than were expected. Meanwhile, our statistical analyses and immunohistochemical evaluation supported the following two hypotheses. First, vertical growth of GP might be affected by progesterone exposure. Second, the origin of GP might be pancreatic islet cells. However, it is strongly suspected that our data have been affected by publication bias and to confirm these hypotheses, further investigation is required.</p