Need for enforcement of ethicolegal education – an analysis of the survey of postgraduate clinical trainees

BACKGROUND: The number of medical lawsuits in Japan was between 14 and 21 each year before 1998, but increased to 24 to 35 per year after 1999. There were 210 lawsuits during this 10-year period. There is a need for skills and knowledge related to ethics, which is as fundamental to the practice of medicine as basic sciences or clinical skills. in Japan education in ethics is relatively rare and its importance is not yet recognized. Establishing ethics education using legal precedents, which has already been achieved in Western countries, will be a very important issue in Japan. In the present study, a questionnaire survey was conducted among graduate intern doctors, in order to investigate whether ethics education using precedents might have a positive effect in Japan. METHODS: In 2002, a questionnaire survey entitled Physicians' Clinical Ethics was carried out in a compulsory orientation lecture given to trainees before they started clinical practice in our hospital. The attendees at this lecture were trainees who came from colleges in various districts of Japan. During the lecture, 102 questionnaires were distributed, completed by attendees and collected. The recovery rate was 100%. The questionnaire consisted of 22 questions (in three categories), of which 20 were answered by multiple choices, and the other two were answered by description. The time required to complete the questionnaire was about 10 minutes. RESULTS: The recovered questionnaires were analyzed using statistical analysis software (SPSS for Windows, Release 10.07J-1/June/2000), in addition to simple statistical analysis. answers using multiple choices for the 20 questions in the questionnaire were input into SPSS. The principal component analysis was performed for each question. As a result, the item that came to the fore was "legal precedent". Since many intern doctors were interested in understanding laws and precedents, learning about ethical considerations through education using precedents might better meet with their needs and interests. CONCLUSION: We applied a new method in which the results of principal component analysis and frequencies of answers to other questions were combined. From this we deduced that the precedent education used in Western countries was useful to help doctors acquire ethical sensitivity and was not against their will. A relationship was found between reading precedents and the influence of lawsuits, and it was thought that student participation-type precedent education would be useful for doctors in order to acquire ethical sensitivity

Reproducibility and validity of food group intake in a short food frequency questionnaire for the middle-aged Japanese population

Purpose: The purpose of this study was to evaluate the reproducibility and validity of a short food frequency questionnaire (FFQ) for food group intake in Japan, the reproducibility and partial validity of which were previously confirmed for nutrients. Methods: A total of 288 middle-aged healthy volunteers from 11 different areas of Japan provided nonconsecutive 3-day weighed dietary records (DRs) at 3-month intervals over four seasons. We evaluated reproducibility based on the first (FFQ1) and second (FFQ2) questionnaires and their validity against the DRs by comparing the intake of 20 food groups. Spearman’s rank correlation coefficients (SRs) were calculated between energy-adjusted intake from the FFQs and that from the DRs. Results: The intake of 20 food groups estimated from the two FFQs was mostly equivalent. The median energy-adjusted SRs between the FFQ1 and FFQ2 were 0.61 (range 0.38–0.86) for men and 0.66 (0.45–0.84) for women. For validity, the median de-attenuated SRs between DRs and the FFQ1 were 0.51 (0.17–0.76) for men and 0.47 (0.23–0.77) for women. Compared with the DRs, the proportion of cross-classification into exact plus adjacent quintiles with the FFQ1 ranged from 58 to 86% in men and from 57 to 86% in women. According to the robust Z scores and the Bland–Altman plot graphs, the underestimation errors in the FFQ1 tended to be greater in individuals with high mean levels of consumption for meat for men and for other vegetables for both men and women. Conclusion: The FFQ demonstrated high reproducibility and reasonable validity for food group intake. This questionnaire is short and remains appropriate for identifying associations between diet and health/disease among adults in Japan

Predictors of dying at home for patients receiving nursing services in Japan: A retrospective study comparing cancer and non-cancer deaths

<p>Abstract</p> <p>Background</p> <p>The combined effects of the patient's and the family's preferences for death at home have in determining the actual site of death has not been fully investigated. We explored this issue on patients who had been receiving end-of-life care from Visiting Nurse Stations (VNS). In Japan, it has been the government's policy to promote end-of-life care at home by expanding the use of VNS services.</p> <p>Methods</p> <p>A retrospective national survey of a random sample of 2,000 out of the 5,224 VNS was made in January 2005. Questionnaires were mailed to VNS asking the respondents to fill in the questionnaire for each patient who had died either at home or at the hospital from July to December of 2004. Logistic regression analysis was respectively carried out to examine the factors related to dying at home for cancer and non-cancer patients.</p> <p>Results</p> <p>We obtained valid responses from 1,016 VNS (50.8%). The total number of patients who had died in the selected period was 4,175 (cancer: 1,664; non-cancer: 2,511). Compared to cancer patients, non-cancer patients were older and had more impairment in activities of daily living (ADL) and cognitive performance, and a longer duration of care. The factor having the greatest impact for dying at home was that of both the patient and the family expressing such preferences [cancer: OR (95% CI) = 57.00 (38.79-83.76); non-cancer: OR (95% CI) = 12.33 (9.51-15.99)]. The Odds ratio was greater compared with cases in which only the family had expressed such a preference and in which only the patient had expressed such a preference. ADL or cognitive impairment and the fact that their physician was based at a clinic, and not at a hospital, had modest effects on dying at home.</p> <p>Conclusions</p> <p>Dying at home was more likely when both the patient and the family had expressed such preferences, than when the patient alone or the family alone had done so, in both cancer and non-cancer patients. Health care professionals should try to elicit the patient's and family's preferences on where they would wish to die, following which they should then take appropriate measures to achieve this outcome.</p

β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development

Abstract β-defensin family plays a role in host defense against viral infection, however its role in HCV infection is still unknown. In this study, we demonstrated that β-defensin 1 was significantly reduced in HCV-infected liver specimens. Treatment with interferon and ribavirin upregulated β-defensin-1, but not other β-defensin tested, with the extent and duration of upregulation associated with treatment response. We investigated β-defensin family expression in liver cancer in publicly available datasets and found that among all the β-defensins tested, only β-defensin 1 was significantly downregulated, suggesting β-defensin 1 plays a crucial role in liver cancer development. Further analysis identified E-cadherin as the top positive correlated gene, while hepatocyte growth factor-regulated tyrosine kinase substrate as the top negative correlated gene. Expression of two proteoglycans were also positively correlated with that of β-defensin 1. We have also identified small molecules as potential therapeutic agents to reverse β-defensin 1-associated gene signature. Furthermore, the downregulation of β-defensin 1 and E-cadherin, and upregulation of hepatocyte growth factor-regulated tyrosine kinase substrate, were further confirmed in liver cancer and adjacent normal tissue collected from in-house Chinese liver cancer patients. Together, our results suggest β-defensin 1 plays an important role in protecting HCV progression and liver cancer development

Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors

BACKGROUND: Somatic mutations in the mitochondrial genome occur in numerous tumor types including brain tumors. These mutations are generally found in the hypervariable regions I and II of the displacement loop and unlikely alter mitochondrial function. Two hypervariable regions of mononucleotide repeats occur in the mouse mitochondrial genome, i.e., the origin of replication of the light strand (O(L)) and the Arg tRNA. METHODS: In this study we examined the entire mitochondrial genome in a series of chemically induced brain tumors in the C57BL/6J strain and spontaneous brain tumors in the VM mouse strain. The tumor mtDNA was compared to that of mtDNA in brain mitochondrial populations from the corresponding syngeneic mouse host strain. RESULTS: Direct sequencing revealed a few homoplasmic base pair insertions, deletions, and substitutions in the tumor cells mainly in regions of mononucleotide repeats. A heteroplasmic mutation in the 16srRNA gene was detected in a spontaneous metastatic VM brain tumor. CONCLUSION: None of the mutations were considered pathogenic, indicating that mtDNA somatic mutations do not likely contribute to the initiation or progression of these diverse mouse brain tumors

Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model

Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30–40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13 Kcal day−1, respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cell-induced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers

TSPO ligand residence time influences human glioblastoma multiforme cell death/life balance

Abstract Ligands addressed to the mitochondrial Translocator Protein (TSPO) have been suggested as cell death/life and steroidogenesis modulators. Thus, TSPO ligands have been proposed as drug candidates in several diseases; nevertheless, a correlation between their binding affinity and in vitro efficacy has not been demonstrated yet, questioning the specificity of the observed effects. Since drug-target residence time is an emerging parameter able to influence drug pharmacological features, herein, the interaction between TSPO and irDE-MPIGA, a covalent TSPO ligand, was investigated in order to explore TSPO control on death/life processes in a standardized glioblastoma cell setting. After 90 min irDE-MPIGA cell treatment, 25 nM ligand concentration saturated irreversibly all TSPO binding sites; after 24 h, TSPO de-novo synthesis occurred and about 40 % TSPO binding sites resulted covalently bound to irDE-MPIGA. During cell culture treatments, several dynamic events were observed: (a) early apoptotic markers appeared, such as mitochondrial membrane potential collapse (at 3 h) and externalization of phosphatidylserine (at 6 h); (b) cell viability was reduced (at 6 h), without cell cycle arrest. After digitonin-permeabilized cell suspension treatment, a modulation of mitochondrial permeability transition pore was evidenced. Similar effects were elicited by the reversible TSPO ligand PIGA only when applied at micromolar dose. Interestingly, after 6 h, irDE-MPIGA cell exposure restored cell survival parameters. These results highlighted the ligand-target residence time and the cellular setting are crucial parameters that should be taken into account to understand the drug binding affinity and efficacy correlation and, above all, to translate efficiently cellular drug responses from bench to bedside