Malignant Hypertension with Thrombotic Microangiopathy.

A 49-year-old man with malignant hypertension, acute kidney injury and mental deterioration was referred to our hospital. We initially observed microangiopathic hemolytic anemia, thrombocytopenia and kidney damage, indicating he had thrombotic microangiopathy (TMA). We considered TMA was caused by malignant hypertension and therefore did not start plasma therapy. The French TMA reference center reported that platelet counts and serum creatine levels have high values for predicting severe ADAMTS13 deficiency. The patient fully recovered from his illness after treatment with antihypertensive drugs and intermittent hemodialysis. This case might thus be useful to understand the proper differential diagnosis and treatment of TMA.

What is the true definition of a "Do-Not-Resuscitate" order? A Japanese perspective.

BACKGROUND: Japan has no official guidelines for do-not-resuscitate (DNR) orders. Therefore, we investigated the effect of DNR orders on physician decision making in relation to performing noncardiopulmonary resuscitation (CPR) and CPR procedures. METHODS: A case-scenario-based questionnaire that included a case of advanced cancer, a case of advanced dementia, and a case of nonadvanced heart failure was administered to physicians. The questions determined whether physicians would perform different non-CPR procedures and CPR procedures in the presence or absence of DNR orders. The number of non-CPR procedures each physician would perform and the number of physicians who would perform each non-CPR and CPR procedure in the absence and presence of DNR ocrders were compared. Physicians from three Japanese municipal acute care hospitals participated. RESULTS: We analyzed 111 of 161 (69%) questionnaires. Physicians would perform significantly fewer non-CPR procedures in the presence of DNR orders than in the absence of DNR orders for all three case scenarios (median [interquartile range] percentages: Case 1: 72% [45%-90%] vs 100% [90%-100%]; Case 2: 55% [36%-72%] vs 91% [63%-100%]; Case 3: 78% [55%-88%] vs 100% [88%-100%]). Fewer physicians would perform non-CPR and CPR procedures in the presence of DNR orders than in the absence of DNR orders. However, considerable numbers of physicians would perform electric shock treatment for ventricular fibrillation in the presence of DNR orders (Case 1: 26%; Case 2: 16%; Case 3: 20%). CONCLUSION: DNR orders affect physician decision making about performing non-CPR procedures. Although some physicians would perform CPR for ventricular fibrillation in the presence of DNR orders, others would not. Therefore, a consensus definition for DNR orders should be developed in Japan, otherwise DNR orders may cause harm.

NF-κB activation via MyD88-dependent Toll-like receptor signaling is inhibited by trichothecene mycotoxin deoxynivalenol.

Macrophages induce the innate immunity by recognizing pathogens through Toll-like receptors (TLRs), which sense pathogen-associated molecular patterns. Myeloid differentiation factor 88 (MyD88), which is an essential adaptor molecule for most TLRs, mediates the induction of inflammatory cytokines through nuclear factor κB (NF-κB). Trichothecene mycotoxin deoxynivalenol (DON) shows immunotoxic effects by interrupting inflammatory mediators produced by activated macrophages. The present study investigates the effect of DON on NF-κB in activated macrophages through MyD88-dependent pathways. DON inhibited NF-κB-dependent reporter activity induced by MyD88-dependent TLR agonists. In addition, lipopolysaccharide-induced phosphorylation of interleukin-1 receptor-associated kinase 1 and inhibitor κBα were attenuated by DON. Furthermore, DON downregulated the expression level of MyD88. These results suggest that DON inhibits NF-κB activation in macrophages stimulated with TLR ligands via MyD88-dependent TLR signals. Therefore exposure to DON may lead to the inhibition of MyD88-dependent pathway of TLR signaling.