Advance Requests of In-patients and Their Families regarding Medical Intervention Practices at the End of Life

Much emphasis is being placed nowadays on Advance Care Planning（ACP）. Under this circumstance, we report on the “advance-request form” prepared by our hospital, along with some relevant considerations. ［Intended Persons and Method］A total of ５３９ newly admitted patients and their families were asked to sign and submit the “advance-request form,” indicating their preferences on the following three kinds of end-of-life interventional practices:（ １）cardiac massage,（２）endotracheal intubation and mechanical ventilation, and（３）use of vasopressors. ［Results］Completed questionnaires were returned by ２１５ male and ３２４ female patients（average age :８２．３ years）. Of the responders, ７２（１４％）indicated their desire for all the three of the aforementioned interventions（［１］,［２］, and［３］）,６５（１２％）indicated their desire for only（１）, ４５（８%）indicated their desire for only（１）and（３）, １４（３%）indicated their desire for only（３）, while the remaining３４１（６３%）requested that none of these to be implemented. Of all the patients, ８７（１６％）patients were able to make their own decisions. ［Conclusion］About ３０％ or more patients and their families indicated their desire for some kind of life-sustaining treatment at the end of life. We believe that ACP only prioritizes a patient’s right to self-determination and that the practice of ACP should not lead to withholding of life-sustaining treatment

Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK-/- and GLUT5-/- mice

Elevated blood fructose concentrations constitute the basis for organ dysfunction in fructose-induced metabolic syndrome. We hypothesized that diet-induced changes in blood fructose concentrations are regulated by ketohexokinase (KHK) and the fructose transporter GLUT5. Portal and systemic fructose concentrations determined by HPLC in wild-type mice fed for 7 days 0% free fructose were 1 mM) with reversed portal to systemic gradients. Systemic fructose in wild-type and KHK(-/-) mice changed by 0.34 and 1.8 mM, respectively, for every millimolar increase in portal fructose concentration. Systemic glucose varied strongly with systemic, but not portal, fructose levels in wild-type, and was independent of systemic and portal fructose in KHK(-/-), mice. With ad libitum feeding for 12 wk, fructose-induced hyperglycemia in wild-type, but not hyperfructosemia in KHK(-/-) mice, increased HbA1c concentrations. Increasing dietary fructose to 40% intensified the hyperfructosemia of KHK(-/-) and the fructose-induced hyperglycemia of wild-type mice. Fructose perfusion or feeding in rats also caused duration- and dose-dependent hyperfructosemia and hyperglycemia. Significant levels of blood fructose are maintained independent of dietary fructose, KHK, and GLUT5, probably by endogenous synthesis of fructose. KHK prevents hyperfructosemia and fructose-induced hyperglycemia that would markedly increase HbA1c levels. These findings explain the hyperfructosemia of human hereditary fructosuria as well as the hyperglycemia of fructose-induced metabolic syndrome

Grand-averaged waveforms of the onset and change-related responses.

Grand-averaged waveforms of the onset responses (A) and change-related responses (B) for each condition. Red arrowheads indicate the sound (A) and change (B) onsets.</p

Amplitude and latency for LDAEP and the change-related response.

LDAEP and the change-related response are shown aligned. On the right are the P50/N100 and N100/P200 amplitudes corresponding to sound pressure and sound pressure changes, respectively, and on the left are the P50, N100, and P200 latencies corresponding to sound pressure and sound pressure changes.</p

Waveforms of a representative subject.

Both the onset and abrupt sound pressure increase evoked a triphasic response with peaks at approximately 50 (P50), 100 (N100), and 200 (P200) ms, with peak amplitudes measured in the time windows of 30–80, 80–150, and 150–280 ms, respectively. The EOG does not affect evoked potentials for either LDAEP or change-related responses. LDAEP, loudness-dependent auditory evoked potentials; ISI, interstimulus interval.</p

Sex differences in LDAEP and the change-related response in P50/N100 and N100/P200.

Differences in correlation coefficients between LDAEP and the change-related response by are shown for the P50/N100 and N100/P200 components. (TIF)</p

Paradoxical Effect of IL-18 Therapy on the Severe and Mild Escherichia coli Infections in Burn-Injured Mice

OBJECTIVE: To investigate the effects of IL-18 therapy on severe and mild bacterial infection after burn injury. SUMMARY BACKGROUND DATA: IL-18 therapy restores IFN-γ production in immunosuppressive mice following burn injury and up-regulate host response to LPS and experimental bacterial peritonitis. On the other hand, the overproduction of IFN-γ could induce an exaggerated inflammation. Therefore, in this study, we focus on the beneficial and deleterious effects of IL-18-induced IFN-γ and investigate the behavior of IL-18 in infections. METHODS: Burn injury was induced in C57BL/6 mice and then they were i.p. injected with IL-18 (0.2 μg) on alternate days. After 1 week, severe and mild infections were made in mice by an Escherichia coli challenge (5 × 10(8) CFU and 1 × 10(8) CFU i.v., respectively). RESULTS: IL-18 therapy decreased the mortality of burn-injured mice followed by a severe infection, whereas it unexpectedly increased the mortality of burned mice with a mild infection. The IL-18 therapy increased the number of liver mononuclear cells (MNCs), especially NK cells, and greatly up-regulated the impaired IFN-γ production from the liver and spleen MNCs in mice with severe infection. Both the serum IFN-γ concentrations recovered while the bacterial count in the liver decreased. In contrast, the serum IFN-γ concentrations of the burned mice with mild infection did not decrease in comparison to the unburned mice, whereas IL-18 therapy greatly up-regulated the serum IFN-γ levels in burned mice. However, IL-18 therapy significantly elevated the serum ALT and creatinine levels, thus suggesting that the mortality was induced by an exaggerated form of shock/multiorgan failure. These beneficial and deleterious effects of IL-18 therapy in mice with severe and mild infections, respectively, were all inhibited by anti-IFN-γ Ab pretreatment. CONCLUSION: IL-18 therapy can be a potent therapeutic tool against severe bacterial infection in immunocompromised hosts, but careful attention should also be paid to its adverse effects