Summary:
1. Modern medical treatments and health care delivery systems can improve length and quality of life, but may only increase suffering and prolong dying if not used properly.
2. Medical ethics can help us understand the importance of patient rights in medical research and choices in medical care and the appropriate use of medical technology.
3. A palliative approach to medical care in chronic severe illness can improve treatment of pain and other symptoms, and provide compassionate, comprehensive care of the patient and family.
4. Open honest communication between the medical care system and patients and families is necessary to achieve quality care at any stage of illness
(abstract in English by Robert Hugo Richardson. MD)

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[in Japanese]

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A good experimental model of thyroid papillary carcinoma has not been available, because of the difficulty to establish a culture cell line of thyroid papillary carcinoma as its slow growth. We studied the pathobiological characteristics of three cell lines, KTC-1, TPC-1 and K-1, which were derived from thyroid papillary carcinoma and compared them with two cell lines of thyroid undifferentiated carcinoma, TTA-1 and TTA-2. The cell growth of KTC-1 was slower than TPC-1 and K1, and that of K-1 was as fast as TTA-1 and TTA-2. Cyto-morphologically, KTC-1 and TPC-1 were uniform. KTC-1 had a polar shape and tended to arrange in follicles. K-1 showed remarkable nuclear pleomorphism with occasional giant cells, and resembled TTA-1 and TTA-2. Immuno-cytochemically, the expression of thyroid transcriptional factor-1 (TTF-1) was seen only in KTC-1. Over-expression of tumor suppressor gene p53 was evident in TTA-1 and TTA-2, but not in KTC-1, TPC-1 and K-1. KTC-1 could be implanted in SCID mice and formed a tumor resembling papillary carcinoma. In contrast, K-1 implanted to nude mice formed tumor resembling poorly-differentiated carcinoma. TPC-1 did not form tumor in both nude and SCID mice. TTA-1 and TTA-2 formed sarcomatous tumor that grew rapidly causing death in a short time. In conclusion, KTC-1 well retained the pathobiological characteristics of thyroid papillary carcinoma, and could provide a useful experimental model for papillary thyroid carcinoma.

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We investigated the clinical characteristics of elderly sclerotic patients showing a high level of ASI (arterial stiffness index) in comparison with patients showing a lower level. Sclerotic outpatients (n = 390, 111 males, 279 females, mean age: 78.1±7.8) complicated by hypertension, diabetes mellitus, cerebral infarction, hyperlipidemia and ischemic heart disease were followed for about 4 years. The ASI was measured non-invasively by computerized oscillometry using CardioVision MS-2000.
A relationship between ASI and age was observed (r = 0.31, p < 0.001) in elderly sclerotic patients. The rate of patients was 29.7% for an ASI less than 70, 36.7% for ASI: 71-140, 17.4% for ASI: 141-210, 7.9% for ASI: 211-280, 4.9% for ASI: 281-350 and 3.3% for ASI more than 351. The death rates among elderly outpatients were compared by ASI level. The rate was 0.0952 (dead/alive: 6/63) for patients showing an ASI more than 211 and was 0.0336 (11/327) for patients showing an ASI less than 210, which was not significantly different by chi-square test. The rate was further calculated by Mantel-Haenszel test stratified by age and sex, showing no significance between two groups. Age and sex were not confounding factors. Similarly, the rate was 0.1250 (4/32) for those with an ASI more than 281, while it was 0.0258 (3/116) for patients showing an ASI less than 70, and the difference was not significant. The Mantel-Haenszel test also did not show a significant difference between those groups. There was no relation between ASI level and the death rate among patients. Finally, we compared disease and laboratory data between the two groups with an ASI showing more than 211 or less than 70. The rate of DM and CKD were significantly higher among patients with an ASI more than 211 group. In patients with an ASI more than 211, values for BUN, Cr, HbA1C, mIMT and Plt Aggre were significantly higher (p < 0.001) than those in patients with an ASI less than 70, while differences in TP, Alb, Cr, CRP, TC and TG were not significant.
It could be concluded that although ASI was not associated with the death rate, it was a thrombogenic predictor even among elderly outpatients.

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Intravenous myocardial contrast echocardiography (MCE) is a useful noninvasive method to evaluate capillary myocardial blood flow and myocardial microcirculation. Dipyridamole (DIP) stress testing is a pharmacologic stress to detect myocardial ischemia by a coronary steal phenomenon and diagnose coronary artery disease (CAD). We evaluated the usefulness and safety of low-dose dipyridamole stress myocardial contrast echocardiography (DIP-MCE) on diagnosing myocardial ischemia in patients with CAD. The subjects were 111 patients consisting of those who had undergone coronary angiography due to suspected CAD such as stable effort angina or asymptomatic myocardial ischemia. Low-dose dipyridamole stress testing was performed with intravenous infusion of dipyridamole 0.56mg/kg. In MCE for this study, the echocardiographic contrast agent, Levovist was administered intravenously, and myocardial perfusion images before and after stress were obtained by the intermittent high mechanical index imaging method to destroy microbubbles, and ultraharmonic imaging to selectively detect and analyze the harmonic signals. Compared to 1 : 6 triggered images before and after stress, patients showing regional myocardial perfusion defect in 1 : 1 triggered images after stress were considered to be those with stress-induced myocardial ischemia. Coronary artery stenosis of more than 70% on coronary angiography was observed in 34 out of 111 patients (45 lesions). The diagnosis rates of coronary artery stenosis lesions of more than 70% on low-dose DIP-MCE were sensitivity 80.0% and specificity 90.3%. The diagnosis rate of each coronary artery lesion was sensitivity 100% and specificity 100% in the left main trunk, sensitivity 85.7% and specificity 90.7% in the left anterior descending artery, sensitivity 75.0% and specificity 89.5% in the right coronary artery, and sensitivity 80.0% and specificity 90.6% in the left circumflex artery. No severe adverse events due to DIP-MCE were observed in any patients, and mild adverse events were noted only in 7 patients (6.3%). This study demonstrated that low-dose DIP-MCE was a highly-safe and useful method to noninvasively and visually evaluate myocardial ischemia due to CAD.

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Although it has been shown that orally administered antigens can induce systemic immune tolerance (i.e., oral tolerance), the underlying detailed mechanism has not yet been elucidated. In this study, we aimed to analyze the dynamics of oral antigens and cellular interactions in Peyer's patches (PPs). Fluorescence-labeled ovalbumin (OVA) was orally administered to BALB/c mice and was found to be captured by dendritic cells (DCs) in the SED region of PPs. When mice were first transferred with OVA-specific naïve T cells derived from OVA-TCR transgenic mice and then orally administered OVA, these mice showed accumulation of T cells in the IFR region of PPs. The accumulated T cells were then collected and analyzed for the pattern of gene expression by real-time PCR, which revealed a gene expression pattern similar to that of FoxP3-positive regulatory T (T_reg) cells. CCR9, an intestinal homing marker, was also strongly expressed. These results suggest that DCs that have captured oral antigens in PPs locally induce antigen-specific naïve T cells to differentiate into T_reg cells with the intestinal homing property.

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