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Background: This study explores the distribution of public awareness, knowledge of availability, and readiness for palliative care services, and the perceived reliability of information resources as part of a nationwide palliative care implementation intervention in Japan (Outreach Palliative Care Trial of Integrated Regional Model [OPTIM]). Methods: A cross-sectional anonymous questionnaire survey was conducted, and 3984 responses were used in the final analysis. Results: A total of 63.1% of respondents admitted having no knowledge about palliative care, while 0.5% of respondents were using palliative care services. Respondents who knew about palliative care services, yet did not know about their availability were 18.6% of all respondents. Respondents who had cancer-related experiences were more likely to be aware of palliative care compared to the general population and availability of palliative care services. Only awareness of palliative care was significantly associated with two typical images, while cancer-related experiences were not. Conclusion: Findings show that the public awareness of palliative care services and their availability is insufficient, and cancer-related experiences affect awareness of cancer palliative care but not directly related to typical images for palliative care such as care for patients close to death. [ABSTRACT FROM AUTHOR]

Abstract: Context: Prognosis is difficult to discuss with patients who have advanced cancer and their families. Objectives: This study aimed to explore the experiences of families of patients with cancer in Japan in receiving prognostic disclosure, explore family perception of the way the prognosis was communicated, and investigate relevant factors of family-perceived need for improvement. Methods: A multicenter questionnaire survey was conducted with 666 bereaved family members of patients with cancer who were admitted to palliative care units in Japan. Results: In total, 86.3% of the families received prognostic disclosure. The overall evaluation revealed that 60.1% of the participants felt that the method of prognostic disclosure needed some, considerable, or much improvement. The parameter with the highest value explaining the necessity for improvement was the family perception that the amount of information provided by the physician was insufficient (beta=0.39, P <0.001). Furthermore, the family perception that they had lost hope and that health care providers failed to facilitate preparation for the patient’s death had significant direct effects on the necessity for improvement (beta=0.21, P <0.001; and beta=0.18, P <0.001, respectively). The feelings for the necessity for improvement also were affected significantly by seven communication strategies (i.e., not saying “I can do nothing for the patient any longer,” pacing explanation with the state of the patient’s and family’s preparation, saying “We will respect the patient’s wishes,” making an effort to understand the family’s distress, being knowledgeable about the most advanced treatments, assuring continuing responsibility as the physician for medical care, and respecting the family’s values). Conclusion: This model suggests that strategies for care providers to improve family perception about prognostic disclosure should include 1) providing as much prognostic information as families want; 2) supporting families’ hopes by keeping up with up-to-date treatments and by assuring the continuing responsibility for medical care; 3) facilitating the preparation for the patient’s death by providing information in consideration of the family’s preparations and values; 4) stressing what they can do instead of saying that nothing can be done for the patient; and 5) assuring the family that they will respect the patient’s wishes. [Copyright &y& Elsevier]

The authors recently demonstrated that the mitochondrial voltage-dependent anion channel 1 (VDAC1) is involved in the sensitivity of cancer cells to furanonaphthoquinone (FNQ). The aim of the present study was to investigate whether mitochondrial VDAC1 reduces quinone antitumor drugs. The VDAC1 purified by immunoprecipitation reduced FNQ in the presence of nicotinamide adenine dinucleotide (NADH) and produced H2O2. Blue native polyacrylamide gel electrophoresis demonstrated that the band that reduced FNQ NADH-dependently mainly included VDAC1. Because H2O2 generation in catalyzing FNQ with NADH caused mitochondrial damage, the cytotoxic activity of FNQ was induced by VDAC1. In the quinone antitumor drugs, menadione (VK3), adriamycin and mitomycin C, mitochondrial VDAC1 bioreductively activated VK3. These results demonstrate that mitochondrial VDAC1 is a pharmacologic target for the treatment of tumor. [ABSTRACT FROM AUTHOR]

Objectives: A psychometric scale for assessing cancer-related worry among cancer patients, called the Brief Cancer-Related Worry Inventory (BCWI), was developed. Methods: A cross-sectional questionnaire survey for item development was conducted of 112 Japanese patients diagnosed with breast cancer, and test–retest validation analysis was conducted using the data from another prospective study of 20 lung cancer patients. The questionnaire contained 15 newly developed items for cancer-related worry, the Hospital Anxiety and Depression Scale, The Impact of Event Scale Revised, and the Medical Outcomes Study Short Form-8. Results: Exploratory factor analysis of the 15 items yielded a 3-factor structure including (1) future prospects, (2) physical and symptomatic problems and (3) social and interpersonal problems. A second-order confirmatory factor analysis identified a second-order factor called cancer-related worry and confirmed the factor structure with an acceptable fit (chi-square (df=87)=160.16, P=0.001; GFI=0.83; CFI=0.92; RMSEA=0.09). The internal consistency and test–retest reliability were confirmed with the lung cancer sample. Multidimensional scaling found that cancer-related worry is separate from anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms. Conclusion: Our study succeeded in developing and confirming the validity and reliability of a BCWI. The study also confirmed the discriminable aspects of cancer-related worry from anxiety, depression, and PTSD symptoms. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Palliative care is an essential part of integrated cancer treatment. To improve palliative care throughout Japan, a nationwide demonstration project, the Outreach Palliative Care Trial of Integrated Regional Model (OPTIM) study, is ongoing. This article reviews the current status and the problems of palliative care in Japan and introduces the OPTIM study. Although the number of palliative care services is increasing, empirical evidence shows the quality of life of cancer patients is still inadequate. The OPTIM study is an intervention trial targeting 4 areas across Japan. Primary end points are quality of care reported by patients as well as the bereaved family, number of patients who received specialized palliative care services, and place of death. The interventions are comprehensively designed to cover all areas identified by the national task force. The OPTIM study will contribute to improve patients' quality of life by proposing a regional palliative care model suitable for Japan. [ABSTRACT FROM AUTHOR]

Background: Although it is important to achieve a good death in Japan, there have been no studies to explore factors associated with a good death. The aim of this study was to explore factors contributing to a good death from the bereaved family members' perspectives, including patient and family demographics and medical variables. Methods: A cross-sectional anonymous questionnaire survey for bereaved family members of cancer patients who had died in a regional cancer center and a medical chart review were conducted. We measured the results from the Good Death Inventory and family demographics. In addition, we extracted patient demographics, medical variables, and medical interventions in the last 48 h before death from a medical chart review. Results: Of the 344 questionnaires sent to bereaved family members, 165 responses were analyzed (48%). We found, first, that death in the palliative care unit was more likely to be described as a good death compared with death on a general ward. Some significant characteristics were ‘environmental comfort,’ ‘physical and psychological comfort,’ ‘being respected as an individual,’ and ‘natural death.’ Second, we found that a patient's and family member's age and other demographic factors significantly correlated with an evaluation of a good death. In addition, life prolongation treatment and aggressive treatment such as chemotherapy in the last 2 weeks of life were barriers to attainment of a good death. Moreover, appropriate opioid medication contributed to a good death. Conclusion: Withholding aggressive treatment and life-prolonging treatment for dying patients and appropriate opioid use may be associated with achievement of a good death in Japan. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the barriers to referral to inpatient palliative care units (PCUs) through a qualitative study across various sources of information, including terminal cancer patients, their families, physicians, and nurses.Materials and Methods: There were 63 participants, including 13 advanced cancer patients, 10 family members, 20 physicians, and 20 nurses in palliative care and acute care cancer settings from five regional cancer institutes in Japan. Semi-structured interviews were conducted regarding barriers to referral to PCU, and data were analyzed by content analysis method.Results: A total of 21 barriers were identified by content analysis. The leading barriers were (1) a negative image of PCUs by patients and families (n = 39), (2) delay of termination of anti-cancer treatment by physicians in the general wards (n = 24), (3) unwillingness to end anti-cancer treatment and denial of the fatal nature of the disease by patients and families (n = 22), (4) patient's wish to receive care from familiar physicians and nurses (n = 20), and (5) insufficient knowledge of PCUs by medical staff in general wards (n = 17).Conclusions: To correct these unfavorable images and misconceptions of PCUs, it is important to eliminate the negative image of PCUs from the general population, patients, families, and medical staffs. In addition, early introduction of palliative care options to patients and communication skills training regarding breaking bad news are relevant issues for a smooth transition from anti-cancer treatment to palliative care. [ABSTRACT FROM AUTHOR]

2-Methyl-naphtho[2,3- b]furan-4,9-dione (FNQ3), a synthetic analogue of the quinone kigelinone, has demonstrated a real potential for use in the treatment of a variety of solid tumours. Unlike other quinones, such as mitomycin-C and adriamycin, the cytotoxicity of FNQ3 is often 10- to 14-fold more potent towards the tumour cells than their normal counterparts. We report, for the first time, that the drug had activity against a broad spectrum of leukaemias and multiple myeloma cells. It decreased the growth of acute myeloid leukaemia (AML) and multiple myeloma cell lines in a dose-dependent fashion (50% inhibitory concentration ≈1·25 μg/ml against most of the leukaemia cell lines). This dose apparently initiated mitochondrial collapse as measured by depolarisation of the mitochondrial membrane. FNQ3 potentiated the differentiation of HL-60 myeloid cells in the presence of either 1 α, 25(OH)2 dihydroxyvitamin D3 [1 α,25(OH)2D3] or all- trans-retinoic acid (ATRA). FNQ3 inhibited the proliferation of primary AML cells while inducing apoptosis. Eleven of 14 (79%) AML marrow samples had a prominent decrease in their clonogenic growth when cultured in the presence of the drug. In summary, this drug has growth inhibitory, apoptotic and differentiative effects against myeloid leukaemias and multiple myeloma cells. FNQ3 may represent a new therapeutic approach to these malignancies. [ABSTRACT FROM AUTHOR]

Background: Although integrated care for existential suffering is an essential part of palliative care, little is known about its concept and efficacy as perceived by professionals. A questionnaire survey was carried out to 1) explore the underlying structure of psychosocial interventions recommended by specialists, 2) identify the professionally perceived effectiveness of each intervention for specific existential distress, and 3) examine the effects of specialty on their recommendations. Methods: A questionnaire with three scenarios representing terminally ill cancer patients with uncertainty-related anxiety, guilt feelings, and dependency-related meaninglessness was mailed to 701 Japanese psychiatrists, 118 psychologists, and 372 palliative care nurses. Results: A total of 456 responses were obtained (response rate=38%). Recommended psychosocial interventions were classified into six subcategories: 'a supportive-expressive approach,' 'providing comfortable environments,' 'meaning-centered approach,' 'being,' 'education and coping skills training,' and 'a religious approach.' A 'supportive-expressive approach' was consistently recommended in all vignettes. On the other hand, 'providing comfortable environments' was most recommended for patients with uncertainty-related anxiety, and a 'meaning-centered approach' and 'being' were most recommended for patients feeling dependency-related meaninglessness. Psychiatrists estimated the effectiveness of psychopharmacological treatment significantly higher than psychologists and nurses, while nurses evaluated efficacy of all other interventions significantly higher than psychiatrists and psychologists. Conclusions: Experts evaluated a variety of clinical interventions as effective in palliating existential suffering, although the perceived levels of efficacy of each intervention differed according to the nature of suffering and their specialties. To effectively alleviate existential suffering in terminally ill cancer patients, an integrated care by an interdisciplinary team is necessary. [ABSTRACT FROM AUTHOR]

There is a strong controversy about the differences among standard medical care, palliative sedation therapy, and euthanasia in recent medical literature. To investigate the similarities and differences among these medical treatments, a secondary analysis of two previous surveys was performed. In those surveys, Japanese physicians and the general population were asked to identify their treatment recommendations or preferences for intolerable and refractory distress in the terminal stage. The options were standard medical care without intentional sedation, mild sedation, intermittent deep sedation, continuous deep sedation, and physician-assisted suicide (PAS)/euthanasia. Multidimensional scaling analysis mapped their responses. The physician responses were clustered into 3 groups: 1) standard medical care, 2) palliative sedation therapy including mild, intermittent deep, continuous deep sedation, and 3) PAS/euthanasia. The general population''s responses were classified into 3 subgroups: 1) standard medical care, 2) mild and intermittent deep sedation, and 3) a group including continuous deep sedation and PAS/euthanasia. Physicians placed continuous deep sedation closer to mild and intermittent sedation, while the general population mapped it closer to PAS/euthanasia. In conclusion, physicians and general population can generally differentiate the three approaches—standard medical care, palliative sedation therapy, and PAS/euthanasia. We recommend that mild and intermittent deep sedation should be differentiated from standard medical care, and that continuous deep sedation should be dealt with separately from other types of sedation. Clear definitions of palliative sedation therapy will contribute to quality discussion. [Copyright &y& Elsevier]

Image analysis quantitation of cytochrome oxidase activity, cytochemicaUy visualized in mitochondria, and the comparison between the activities of pulmonary alveolar Type I and Type II cells were performed. Normal lungs of rats were fixed with 2% glutaraldehyde for 10 min at 4°C and then small blocks were incubated for 60 min at 37°C in a medium containing 1.0 mg/ml (2.8×l0M) 3,3′-diamiDobcnzidlnc-tctrahydrochloride, 1 mg/ml cytochrome c, 0.1 mg/ml catalase, 7% sucrose and 0.1 M phosphate buffer at pH 7.4. The intermembrane space, between the outer and inner membranes, and intracristal space of Type II cell mitochondria were filled with deposits whose mean volume was 0.047 μm. Type I cell mitochondria were smaller in size than those of Type II cells, but because reaction deposits were not fully accumulated within the spaces the resulting net deposit volume was 0.00182 μm If the intermembrane spaces of Type I cell mitochondria had been thoroughly filled by the deposits, the mean volume would have been 0.00248 μm. These results indicate that stereoscopic image analysis of the reaction product is appropriate in the quantitation of cytochemicaUy visualized enzyme activity, and furthermore suggest that Type I cells may be rather deficient in cytochrome oxidase activity. [ABSTRACT FROM PUBLISHER]

Ultrastructural and cytochemical changes in rat livers after paraquat administration were Investigated. A single intraperitoneal injection of 150 mg/ kg paraquat dichioride caused primary toxicological changes in the hepatocyte mitochondria., such as decrease in the electron density of the matrices, disintegration of crlstae, disappearance of intramitocliondrial granules, and irreversible swelling. Ca-ATPase activity in those mitochondria disappeared. experiments, the activity of fixed normal livers was significantly inhibited by 10 mM paraquat. No significant effect on the plasma membrane Ca-ATPase activity was observed. These results suggest that the mitochondrial damage caused by paraquat may be related to the possible inhibition of their Ca-ATPase activity, resulting in cell injury. [ABSTRACT FROM PUBLISHER]

A high incidence of cytoplasmic pore complex similar to Maul's (, 104: 233, 1977) was found in the cultured myeloblastic leukemic cells, Ml line, clone 264-2. The pore complex was composed of one to four pores perforating a single cisterna of the endoplasmic reticulum. When the blastic M1 cells were cultured in the presence of a conditioned medium, they successfully differentiated into macrophages. This resulted in a loss of malignancy, and simultaneously the pore complex changed to the stacked annulate lamellae. The well-developed annulate lamellae were also generally found in the cytoplasm of the cloned macrophages. Mm-1 subline was derived from the M1 line by spontaneous differentiation, and the cells appeared less transplantable to animals. These results indicate that myeloblastic M1 cells possess the simple pore complex, which may develop into the annulate lamellae during cell differentiation into macrophages. [ABSTRACT FROM PUBLISHER]

Although the intracellular toxic sites of paraquat, a herbicide toxic to human bodies, have remained unclear for a long time, we recently demonstrated paraquat-induced mitochondrial injury in rat lung and liver . In the present study, cultured human lung cells (A549 adenocarcinoma cell line) which received 0.15 mM paraquat (equivalent to 40 mg/kg i.v.) showed selective mitochondrial breakage at 6–24 hr and died at 36–48 hr. These results suggest that mitochondria are the initial toxic site of paraquat as well as in contrast to the previously proposed microsome theory. [ABSTRACT FROM PUBLISHER]

The cytochrome oxidase activity of rat dorsal root ganglion cells was cytochemically and quantitatively measured. The 100 μm thick tissue slices fixed for 10 min were incubated in a DAB medium for 0, 30, 60, and 90 min at 37°C, and electron-dense deposit areas within the mitochondrial intermembrane-intracristal spaces were measured with a computer-controlled image analyzer. The activity was expressed as deposit accumulation rate filling the mitochondrial space, (1 unit corresponds to the deposit filling 100% of the mitochondrial space per hour). Three different activities of the enzyme in either large pale cells or small dark cells of sensory neurons could be distinguished, based on the quantitative analysis, as large cells with intense (0.83 units), intermediate (0.38), and weak activity (0.22), and small cells with the same degrees of activity (1.04, 0.35, and 0.11, respectively). The results indicate that accumulation rate measurements of reaction product may be useful to quantitatively present the cytochrome oxidase reactivity of mitochondria, and that the degree of enzyme activity may contribute to the identification of functional differences in sensory neurons. [ABSTRACT FROM PUBLISHER]

Cytochemically demonstrated cytochrome oxidase activities in mitochondria of rat pulmonary alveolar epithelial cells were quantitatively compared. As the standardized procedures, lungs were fixed for 10 mm at 4°C with 2% pure glutaraldehyde, and incubated for different times at 37°C in a medium containing 1.0 mg/ml 3,3'-diaminobenzidine-4HCl, 1 mg/ml cytochrome c, 0.1 mg/ml catalase, 7% sucrose, anb 0.1 M phosphate buffer, pH 7.4. Electron micrographs were then odtained, and the densities of the reaction deposits in the mitochondrial intermembrane-intracristal space were measured in an image analyzer, and were plotted in terms of time in minutes. The initial velocity (maximal rate) of the activity expressed as deposit accumulation rate (% area/60 min) filling the mitochondrial intermembrane-intracristal space of Type I, Type II and Type III cells was 40, 130 and 9.3, respectively. These results indicated that mitochondria are varied in the intensity of cytochrome oxidase activity among 3 types of pulmonary alveolar epithelial cells, and that the image-analyzing measurement of the accumulation rate of reaction product may be useful for quantitative analysis of enzyme activity, in particular, in the cells which are difficult to isolate from complex tissues. [ABSTRACT FROM PUBLISHER]

The ultrastructural localization of uterine peroxidase activity in the human endometrium was studied. Very weak peroxidase activity was present in a few surface nonciliated cells with very weak activity in the early proliferative phase; the activity was enhanced and distributed throughout the nonciliated cells during the late proliferative to secretory phase. The activity was observed in the endoplasmic reticulum and nuclear envelope but not in the secretory granules and Golgi apparatus. The surface ciliated cells and all glandular cells were entirely devoid of the activity throughout the menstrual cycle. Nucleolar channel system was transiently formed in the surface and glandular nonciliated cells in the postovulatory phase. The channels of the system in the surface cells showed intense peroxidase activity, but those in the glandular cells were negative. These results indicate that the human uterine peroxidase activity appears only in the superficial nonciliated cells and changes in its intensity depending on the menstrual cycle, and that the nucleolar channel system is closely related with the nuclear envelope showing peroxidase activity. [ABSTRACT FROM PUBLISHER]