A report on small team clinical ethics consultation programmes in Japan.

Clinical ethics support, including ethics consultation, has become established in the field of medical practice throughout the world. This practice has been regarded as useful, most notably in the UK and the USA, in solving ethical problems encountered by both medical practitioners and those who receive medical treatment. In Japan, however, few services are available to respond to everyday clinical ethical issues, although a variety of difficult ethical problems arise daily in the medical field: termination of life support, euthanasia and questions about patient autonomy. In light of these conditions, a group of 17 volunteer educators and researchers from the area of biomedical ethics, including the authors, have formed the Clinical Ethics Support and Education Project, and began providing Japan's first small team clinical ethics consultation service in October, 2006. Members include scholars of biomedical ethics, scholars of philosophy and ethics, legal professionals and legal scholars, nurses and doctors, consisting of five women and 12 men. Consultation teams, made up of a small number of members, were organised each time a request for consultation was received. Over approximately 15 months (October 2006-December 2007), the programme received 22 consultation requests from medical practitioners and medical institutions, and three from the families of patients. In this paper, we will discuss the status of our consultation service and examples of consultation cases we have handled. In addition, we will examine the process of evaluating small team clinical ethics consultation services, as well as the strengths and weakness of such programmes.

Dietary intake and urinary excretion of selenium in the Japanese adult population: the INTERMAP Study Japan.

OBJECTIVE: This study is to examine the relationship between dietary selenium intake and 24-h urinary selenium excretion in Japanese population samples participating in the INTERMAP Study. METHODS: Using highly standardized methods, we assessed individual dietary selenium intake from four 24-h dietary recalls and measured urinary selenium excretion in two timed 24-h urine collections in 1145 Japanese participants (574 men and 571 women) ages 40-59 years in four areas of Japan. RESULTS: The medians of dietary selenium intake were 177.5 microg/day in men and 139.8 microg/day in women; the medians of 24-h urinary selenium excretion were 127.9 microg/day in men and 109.4 microg/day in women, that is, urinary excretion was estimated to be 73% of dietary intake in men and 77% in women. Dietary selenium intake was significantly correlated with 24-h urinary selenium excretion (r=0.24 in men, r=0.18 in women; P<0.001). With dietary selenium intake and urinary selenium excretion expressed per kg of body weight, values were similar for men and women (dietary intake, 2.7 microg/kg body weight in men and 2.5 microg/kg body weight in women; urinary excretion, 2.0 microg/kg body weight in men and 2.0 microg/kg body weight in women). CONCLUSION: Dietary intake and 24-h urinary excretion of selenium are related in the Japanese adult population.

How do bioethics teachers in Japan cope with ethical disagreement among healthcare university students in the classroom? A survey on educators in charge.

OBJECTIVE: The purpose of this study was to demonstrate how educators involved in the teaching of bioethics to healthcare university students in Japan would cope with ethical disagreement in the classroom, and to identify factors influencing them. METHODS: A cross sectional survey was conducted using self administered questionnaires mailed to a sample of university faculty in charge of bioethics curriculum for university healthcare students. RESULTS: A total of 107 usable questionnaires were returned: a response rate of 61.5%. When facing ethical disagreement in the classroom, coping behaviour differed depending on the topic of discussion, was influenced by educators' individual clear ethical attitudes regarding the topic of discussion, and was independent of many respondents' individual and social backgrounds. Among educators, it was commonly recognised that the purpose of bioethics education was to raise the level of awareness of ethical problems, to provide information about and knowledge of those issues, to raise students' sensitivity to ethical problems, and to teach students methods of reasoning and logical argument. Yet, despite this, several respondents considered the purpose of bioethics education to be to influence students about normative ethical judgments. There was no clear relationship, however, between ways of coping with ethical disagreement and educators' sense of the purpose of bioethics education. CONCLUSIONS: This descriptive study suggests that educators involved in bioethics education for healthcare university students in Japan coped in various ways with ethical disagreement. Further research concerning ethical disagreement in educational settings is needed to provide better bioethics education for healthcare students.

Keratinocyte gene therapy: inducible promoters and in vivo control of transgene expression.

Modulation of transgene expression by exogenous agents is an optimal goal in gene therapy. Successful keratinocyte gene therapy requires a promoter-enhancer cassette to regulate expression of the therapeutic gene in vivo. In this study, we first transferred plasmids, constructed by introducing inducible promoters fused to the beta-galactosidase gene (LAC Z), into keratinocytes in vitro. Metallothionein (MT) and 1,24-vitamin D(3)(OH)(2) dehydroxylase (VDH) promoters responded to the inducing agents, Cadmium and 1,25-vitamin D(3)(OH)(2) (VitD(3)), respectively. The plasmids were then introduced in vivo using a naked DNA method and the inducible promoters were evaluated by measuring beta-gal activity in rat keratinocytes. Zinc induced the transferred MT promoter activity by approximately 2-fold or 10-fold when administered systemically and topically, respectively. In addition, VitD(3) induced the transferred VDH promoter activity approximately 10-fold when administered topically. These data are useful for developing inducible promoters for keratinocyte gene therapy.

Highly sensitive and rapid method for determination of fluoride ion concentrations in serum and urine using flow injection analysis with a fluoride ion-selective electrode.

An apparatus for flow injection analysis (FIA) was developed to measure very low fluoride ion concentrations (<1 micromol/l). The analytical conditions of the apparatus were investigated, and the instrument was used to determine fluoride ion concentrations in serum and urine. All interferences caused by serum and urine matrices were eliminated using the proposed method. The recovery was almost 100.0% for serum and urine samples. The precision was within 4%. The results of determination of fluoride ion concentrations in the NIST Standard Reference Material of urine, SRM 2671a, agreed with the certified values. The detection limits in serum and urine were 0.016 and 0.16 micromol/l, respectively. The assay throughput was 15 samples/h in serum and 24 samples/h in urine. The mean fluoride ion concentrations in serum and urine samples from 53 young Japanese women were 0.383+/-0.158 micromol/l and 0.207+/-0.103 mg/g Cr, respectively. There was a significant correlation (r=0.39, p<0.01) between serum and urine fluoride ion concentrations.

In vivo gene introduction into keratinocytes using jet injection.

Successful keratinocyte gene therapy requires the development of efficient methods of gene transfer to keratinocytes. Jet injection of a solution containing DNA can be used to transfer genes to several tissues in vivo. In this article, we tried to introduce DNA into rat and human keratinocytes using this method. First, we fired a beta-gal expression vector into rat skin at several distances using a jet injector and examined beta-gal activity in the epidermal keratinocytes. The highest activity in keratinocytes was found when the plasmid was fired at 10 cm from the skin surface; the activity lessened as the firing distance became shorter than 10 cm. Next, we transplanted human skin on to a nude rat, fired the vector into the human skin from a distance of 10 cm and examined the beta-gal activity. We also injected the same amount of plasmid with a needle to compare jet with needle injections. The results showed that jet injection of the naked DNA could introduce and express DNA in human keratinocytes in vivo and that jet injection exhibited much higher activity than needle injection. Jet injection of the naked DNA will provide a method for keratinocyte gene therapy in the future.

Synthesis of bis-netropsin-linked hydroxamic acids and their DNA cleavage properties in the presence of transition or lanthanide metal ions.

Nobel hydroxamic acids containing bis-netropsin units coupled by polymethylenetether (BNHA) have been synthesized. BNHA-ferrous complexes sequence-specifically cleaved pBR322 DNA fragment whereas corresponding cerium complexes showed low-sequence specific cleavage pattern.

[Serum inorganic fluoride concentrations and their urinary excretion during and after sevoflurane, isoflurane, or enflurane anesthesia in man].

Serum inorganic fluoride concentrations and their urinary excretion were examined during and after sevoflurane, isoflurane, or enflurane anesthesia in man. Duration of anesthesia was 3 hours in sevoflurane and enflurane groups (S3 group: n = 10, E3 group: n = 5), and 3 or 5 hours in isoflurane groups (I3 group: n = 5, I5 group: n = 5). Serum inorganic fluoride concentration of the S3 and E3 groups increased immediately following induction, and reached the maximum concentration of 21.8 +/- 9.3 (M +/- SD) mumol.l-1 (S3), 13.6 +/- 6.2 mumol.l-1 (E3) at 1 hour after anesthesia. Serum inorganic fluoride decreased after the peak concentrations, and returned to the pre-anesthesia level at 96 hours (S3) and 144 hours (E3) after anesthesia. On the other hand, serum inorganic fluoride of the I3 and I5 groups scarcely changed from the pre-anesthesia level, and maximum concentrations of these two groups were one tenth of the S3 group. Urinary excretion of inorganic fluoride of the S3 and E3 group began to increase from 2 hours after anesthesia, and showed plateau of 60-90 mmol.h-1 from 12 hours to 24 hours after anesthesia. The change of serum inorganic fluoride sharply contrasted with urinary excretion. Our results suggest that fluoride excretion is largely carried out by the kidney. Therefore sevoflurane or enflurane anesthesia should be avoided in patients with renal dysfunction.

[Micro-determination of fluoride in biological samples by pyrohydrolysis and flow-injection analysis using a fluoride ion-selective electrode].

An apparatus has been developed for the isolation of fluoride in biological samples through pyrohydrolysis. With this apparatus, it is possible to determine both organic and inorganic fluorocompounds with a recovery close to 100% and precision within 5%. The high recovery rate can be expected even for highly heat-resistant compounds such as CaF2, without using WO3 as a catalyst. For determination of the isolated fluoride, a separate apparatus was developed in which flow-injection analysis was used in conjunction with a fluoride ion-selective electrode as a detector. With this apparatus, fluoride in a sample solution with a volume as small as 0.2 ml, and at a concentration as low as 0.5 microgram/l, can be determined within 3 minutes with a precision of several percent. Combined use of the two apparatuses makes it possible to determine fluoride in different biological samples within 10-15 minutes with a precision of several percent, free from external contamination. By selecting suitable conditions for analysis and using a 1 g sample, it is possible to determine fluoride at a concentration as low as 5 ng/g. By employing these apparatuses, the fluoride content in different biological samples has been determine and the effectiveness of their use confirmed.