Thiamine deficiency as a cause of anorexia in terminally ill cancer patients: A case of possible gastrointestinal beriberi.

OBJECTIVES: Anorexia in cancer patients has a variety of causes and impairs patients' quality of life. However, there have been few reports of thiamine deficiency (TD) playing a role in anorexia during palliative care. The objective of this report was to describe such a case. METHODS: An 82-year-old woman with advanced cervical cancer was admitted for palliative care because of progressive disease. One month after admission, she developed myoclonus on the left side, difficulty speaking, slurred speech, and drooping of the left corner of the mouth, with no consciousness disturbance. She also developed nausea and complained of decreased dietary intake for more than 2 weeks. RESULTS: The patient's thiamine level, which had been measured 2 weeks earlier, was 27 ng/ml, which was below the normal range, and 100 mg of thiamine was administered intravenously. After 2 hours, the patient's neurological findings resolved, and her dietary intake improved from 30% to 40% of meals to 90% to 100%. Subsequently, the patient did not experience similar symptoms, and her clinical course was stable. Based on the patient's clinical course, gastrointestinal beriberi was diagnosed. SIGNIFICANCE OF RESULTS: This case shows that TD may cause anorexia. Many patients who receive palliative care have decreased dietary intake. Consequently, such patients may present with gastrointestinal beriberi, as in the present case. Appropriate diagnosis and treatment may contribute to increasing such patients' quality of life. It may be necessary to differentiate TD from other conditions as a cause of anorexia in patients receiving palliative care.

Identification of Chemicals That Abrogate Folate-Dependent Inhibition of Starch Accumulation in Non-Photosynthetic Plastids of Arabidopsis.

Folate, also known as vitamin B9, is an essential cofactor for a variety of enzymes and plays a crucial role in many biological processes. We previously reported that plastidial folate prevents starch biosynthesis triggered by the influx of sugar into non-starch-accumulating plastids, such as etioplasts, and chloroplasts under darkness; hence the loss of plastidial folate induces the accumulation of starch in plastids. To understand the molecular mechanism underlying this phenomenon, we screened our in-house chemical library and searched their derivatives to identify chemicals capable of inducing starch accumulation in etioplasts. The results revealed four chemicals, compounds #120 and #375 and their derivatives, compounds #120d and #375d, respectively. The derivative compounds induced starch accumulation in etioplasts and suppressed hypocotyl elongation in dark-grown Arabidopsis seedlings. They also inhibited the post-germinative growth of seedlings under illumination. All four chemicals contained the sulfonamide group as a consensus structure. The sulfonamide group is also found in sulfa drugs, which exhibit antifolate activity, and in sulfonylurea herbicides. Further analyses revealed that compound #375d induces starch accumulation by inhibiting folate biosynthesis. By contrast, compound #120d neither inhibited folate biosynthesis nor exhibited the herbicide activity. Protein and metabolite analyses suggest that compound #120d abrogates folate-dependent inhibition of starch accumulation in etioplasts by enhancing starch biosynthesis.

Palliative care unit treatment and care for a terminal breast cancer patient with untreated obsessive-compulsive disorder.

OBJECTIVES: Although palliative care units treat patients with various comorbidities, there are no reports of patients with obsessive-compulsive disorder (OCD). METHODS: The treatment and care of a breast cancer patient with OCD are presented. RESULTS: A woman in her 40s was admitted to the palliative care unit for terminal breast cancer. She spent most of the day cleaning the bath and bed areas, ignoring efforts to restrain her actions by the staff. After being diagnosed with OCD, the above symptoms improved through the coordinated action of the staff and medication. SIGNIFICANCE OF RESULTS: This is the first report of the diagnosis and treatment of a patient with OCD in a palliative care unit. Early psychiatric diagnosis and subsequent staff response contributed to improvement in the patient's quality of life.

Bathing in Terminal Care of Cancer Patients and Its Relation to Perceptions of a "Good Death": A Nationwide Bereavement Survey in Japan.

Background: Bathing in a tub is integral to Japanese culture. It improves palliative care patients' symptoms and may improve quality of life. Objectives: This study aimed to determine the prevalence and impressions of bathing for terminally ill cancer patients and its relations to the evaluations of perceived end-of-life care and achievement of a good death. Design: This was a cross-sectional, anonymous, self-report questionnaire survey. Setting/Subjects: The questionnaire for this study was sent to bereaved family members who had lost loved ones in 14 general hospitals and 187 palliative care wards in Japan. Measurements: The bereaved family members of the patients who had actually bathed were asked about their impression of bathing. The short version of the Good Death Inventory (GDI) and the Care Evaluation Scale were used to evaluate "achievement of a good death." In total, 1819 surveys were sent between July and September 2018 to bereaved family members of patients who had died between February 2014 and January 2018 in 14 general hospitals and 187 palliative care wards in Japan. Overall 885 questionnaires (valid response rate 48%) returned by bereaved family members were analyzed. Results: Overall, 85% of bereaved family members of patients who bathed evaluated the experience positively, 86% reported that the patient's face seemed to become calm after the bath, and 28% of bereaved family members whose loved one had not bathed reported regretting it. The total GDI score for the bereaved family's desired death was 82.7 ± 13.0 for the bathing group and 75.4 ± 15.7 for the no bathing group, a significant difference (effect size = 0.52, p < 0.01). Conclusions: Bathing before death was evaluated positively and was associated with the achievement of a good death.

Effects of Bathing in a Tub on Physical and Psychological Symptoms of End-of-Life Cancer Patients: An Observational, Controlled Study.

This observational, controlled study explored the effects of bathing on the physical and psychological aspects of terminal cancer patients on a palliative care ward. With nurses' assistance, the patients evaluated and recorded the severity of their symptoms at 10:00 am, 30 minutes after initial bathing, and at 5:00 pm. The bathing care was provided as routine care according to the patients' wishes. Twelve symptoms were measured using 9 items (numbers 1-9) from the Edmonton Symptom Assessment System-Revised Japanese version and 3 items from the Cancer Fatigue Scale. Outcomes were compared between bathing days and nonbathing days (control) and between before and after bathing. Of the 57 bathers, data were available for both bathing days and nonbathing days for 42 bathers. In the comparison between bathing and nonbathing days, tiredness was significantly improved (effect size [ES], 0.35; P = .02). On the basis of the pre-post bathing comparison, 6 symptoms, namely, tiredness (ES, 0.40; P < .01), lack of appetite (ES, 0.36; P = .01), decreased well-being (ES, 0.33; P = .01), anxiety (ES, 0.36; P = .01), pain (ES, 0.31; P = .02), and depression (ES, 0.30; P = .02), were significantly improved. Bathing in a tub effectively improves tiredness and might be effective for distressing symptoms in end-of-life cancer patients.

Good death and bereavement in a lung cancer patient following meaning-centered couples psychotherapy by a cancer nursing specialist.

OBJECTIVE: There are many terminally ill cancer patients who are struggling with the meaning of life, but it cannot be said that their concerns are being adequately addressed. METHOD: From a series of cancer patients undergoing end-of-life care, the case of a patient, who developed incurable lung cancer and, together with his wife, lost the meaning of life and underwent meaning-centered couples psychotherapy once every two weeks to have them consider the meaning of life together, is presented. RESULTS: The patient was a 70-year-old man who had been diagnosed with lung cancer and pleural dissemination 14 months earlier. The meaning-centered psychotherapy (MCP) sessions were conducted with the patient and his 70-year-old wife by a cancer nursing specialist who had received extensive training in MCP and had also received 7-year on-going supervision from a Japanese MCP-enlightened psychologist. At the same time, palliative treatment of physical distress was performed. The patient was able to discover the meaning of life as a result of MCP performed by a cancer nursing specialist for him and his spouse who had lost any notion of the meaning of life after being informed that he had terminal cancer at the time of the initial diagnosis. SIGNIFICANCE OF RESULTS: Meaning-centered psychotherapy provided to terminal cancer patients by cancer nurses can help patients and their families express their gratitude, thereby achieving a good death for the bereaved family. Nurses are likely to increasingly perform MCP in the future.

The Principles of Revised Clinical Guidelines about Palliative Sedation Therapy of the Japanese Society for Palliative Medicine.

Background: When the suffering of a terminally ill patient is intolerable and refractory, sedatives are sometimes used for symptom relief. Objective: To describe the main principles of revised Japanese clinical guidelines about palliative sedation therapy. Design: Consensus methods using the Delphi technique were used. Results: The main principles of the guidelines that were newly defined or developed are as follows: (1) palliative sedation was defined as "administration of sedatives for the purpose of alleviating refractory suffering" (excluding the aim of reducing patient consciousness); (2) palliative sedation was classified according to the method of administration of sedatives: respite sedation versus continuous sedation (including (continuous) proportional sedation and continuous deep sedation); (3) a description of state-of-the-art recommended treatments for difficult symptoms such as delirium, dyspnea, and pain before the symptom was determined as refractory was included; (4) the principle of proportionality was newly defined from an ethical point of view; and (5) families' consent was regarded as being desirable (mandatory in the previous version). Conclusions: We described the main principles of revised Japanese clinical guidelines about palliative sedation therapy. Further consensus building is necessary.

[Trends in admission to a new palliative care unit from home and subjects for the future].

We investigated the trend in admission to new a palliative care unit (PCU) over 9 months. We observed a significant difference in the length of PCU stay depending on whether patients had access to a house call doctor. These findings suggest that house call doctors play an important role in ensuring a smooth admission to the PCU. In addition, our study suggests that review of the operational management in the PCU is required.

Preventive effect of a traditional herbal medicine, Hochu-ekki-to, on immunosuppression induced by surgical stress.

PURPOSE: To examine the effect of preoperative administering of a Japanese traditional herbal medicine, Hochu-ekki-to (TJ-41), on immunosuppression induced by surgical stress in patients with gastrointestinal malignancies. METHODS: To monitor the immune functions, the mitochondrial membrane potential (MMP) and natural killer (NK) cell activity prior to and following operation were measured in peripheral blood lymphocytes (PBL) in patients with (n = 20) or without (n = 27) the preoperative administering of TJ-41 for 7 days. The plasma catecholamine and interleukin (IL)-6 levels were also analyzed prior to and following the operation. RESULTS: The numbers of MMP-high CD56-positive cells (NK cells) and NK cell activities in the TJ-41-treated group were significantly higher than those in the control group (P = 0.026 and P = 0.037, respectively). An elevation of plasma noradrenaline and IL-6 following surgery was also inhibited by the preoperative administering of TJ-41 (P = 0.023 and P = 0.039, respectively). A positive correlation between MMP-high CD56-positive cell numbers and NK cell activity in PBL treated with carbonyl cyanide m-chlorophenyl hydrazone (CCCP) in vitro suggested that MMP measurement in CD56-positive cells can serve as a convenient alternative to evaluate the NK cell activity. CONCLUSION: Our findings suggest that the preoperative administering of TJ-41 prevents surgical stress-induced immunosuppression by maintaining the NK cell activity and inhibiting the elevation of stress mediators.

Insertional mutagenesis by the Tol2 transposon-mediated enhancer trap approach generated mutations in two developmental genes: tcf7 and synembryn-like.

Gene trap and enhancer trap methods using transposon or retrovirus have been recently described in zebrafish. However, insertional mutants using these methods have not been reported. We report here development of an enhancer trap method by using the Tol2 transposable element and identification and characterization of insertional mutants. We created 73 fish lines that carried single copy insertions of an enhancer trap construct, which contained the zebrafish hsp70 promoter and the GFP gene, in their genome and expressed GFP in specific cells, tissues and organs, indicating that the hsp70 promoter is highly capable of responding to chromosomal enhancers. First, we analyzed genomic DNA surrounding these insertions. Fifty-one of them were mapped onto the current version of the genomic sequence and 43% (22/51) were located within transcribed regions, either exons or introns. Then, we crossed heterozygous fish carrying the same insertions and identified two insertions that caused recessive mutant phenotypes. One disrupted the tcf7 gene, which encodes a transcription factor of the Tcf/Lef family mediating Wnt signaling, and caused shorter and wavy median fin folds and pectoral fins. We knocked down Lef1, another member of the Tcf/Lef family also expressed in the fin bud, in the tcf7 mutant, and revealed functional redundancy of these factors and their essential role in establishment of the apical ectodermal ridge (AER). The other disrupted the synembryn-like gene (synbl), a homolog of the C. elegans synembryn gene, and caused embryonic lethality and small pigment spots. The pigment phenotype was rescued by application of forskolin, an activator of adenylyl cyclase, suggesting that the synbl gene activates the Galpha(S) pathway leading to activation of adenylyl cyclase. We thus demonstrated that the transposon-mediated enhancer trap approach can indeed create insertional mutations in developmental genes. Our present study provides a basis for the development of efficient transposon-mediated insertional mutagenesis in a vertebrate.

Serum nutritional status of tocopherol and retinol normalized to lipids of persons living in the southern rural Terai region in Nepal.

OBJECTIVE: The present study examined the levels of serum α-Tocopherol (Toc), retinol (Ret), cholesterol (Chol) and triglycerides (TG), and their correlations in the sera of people in Nepal. METHODS: The survey was conducted on the general populace in the agricultural Terai region in southern Nepal. The study population consisted of 93 males and 83 females aged 10-68 years. Serum Toc and Ret were measured by high-performance liquid chromatography. RESULTS: No significant differences were observed between the genders for the average of total Chol (T-Chol) (140 and 145 mg/100 ml, respectively), HDL-C (45 and 47 mg/100 ml), LDL-C (94 and 97 mg/100 ml), and TG (106 and 110 mg/100 ml), and the ratio of LDL/HDL (2.16). The levels of mean Toc (4.32 and 4.27 µg/ml) were about the same for both genders, while the mean Ret levels were significantly higher for males (624 ng/ml) than for females (535 ng/ml) (p<0.001). A direct relationship was found between the levels of Toc and Ret (r=0.46, p<0.001 and r=0.28, p<0.05 for males and females, respectively). Serum levels of Toc and Ret were positively related to the levels of Chol (r=0.48 and r=0.58, p<0.001 for males and r=0.49, p<0.01 and r-0.28, p<0.05 for females, respectively). The ratio of Toc/TG normalized to serum TG was directly correlated to the ratio of Ret/TG (r=0.79 for males, and r=0.72 for females, p<0.001, respectively) and the ratios of Toc/TG and Ret/TG were negatively related to the LDL/HDL levels (r=-0.49 and r=-0.43, for males, and r=-0.46 and r=-0.57 for females, p<0.001, respectively). CONCLUSION: The levels of Toc and Ret were low in the sera of people living in the southern rural Terai region in Nepal, and it was found that lower levels of Toc and Ret normalized to TG increased the ratio of LDL/HDL. These results suggest that greater intake of foods rich in Toc and Ret should be encouraged to reduce the erisk of coronary heart disease.