Predictive variables for hemodialysis and death in Japanese spotted fever, and the association between distance from rivers and incidence.

The number of patients with Japanese spotted fever (JSF) and its case fatality rate have been increasing in Japan and other East Asian countries. Better clinical and laboratory biomarkers are needed to avoid misdiagnosing JSF and to predict severe cases. In addition to determining these predictors, we aimed to examine the association between the incidence of JSF and the distance from rivers, in Hiroshima Prefecture, one of the most JSF prevalent areas in Japan. Patients diagnosed with JSF from 2009 to 2017 in two hospitals in Onomichi City in Hiroshima Prefecture were studied, and their clinical characteristics and laboratory data were collected retrospectively from medical charts. A random forest was used to identify predictors of severe JSF leading to hemodialysis or death. A multivariable negative binomial regression model was utilized to analyze the association between the cumulative incidence in each postal code area and the distance from the residential postal code area to the closest river. Out of 82 patients with JSF (mean age at diagnosis, 74.1 ± 10.6 years; 34 (41.5 %) men), 6 cases were regarded as severe (among them 5 hemodialysis patients and 3 deaths). Twenty-eight (34.1 %) patients were misdiagnosed at least once at the initial hospital visit. Laboratory examination showed 34.5 % had atypical lymphocytes, 73.8 % had no eosinophils, 75.6 % had an elevated aspartate aminotransferase (AST) level, and 69.5 % had hyponatremia. Among cases without urine leucocytes, 63.3 % had proteinuria and 63.3 % had hematuria. Low serum total protein was the strongest predictor of severe JSF, followed by high blood urea nitrogen (BUN) and low albumin. Geospatial analysis showed a significant negative association between the cumulative incidence of JSF cases and the distance from rivers in an adjusted model: the cumulative incidence decreased by 0.51 times (95 % CI: 0.30 to 0.86) for every kilometer of distance from the residential postal code area to the closest river. Some laboratory data may be useful in averting misdiagnosis of JSF and in predicting severe cases. Additional studies should be done in order to clarify the mechanism and association of the incidence of JSF with the distance from the nearest river.

Prediction of Disseminated Intravascular Coagulation by Liver Function Tests in Patients with Japanese Spotted Fever.

Objective Cases of Japanese spotted fever (JSF) are sometimes complicated by disseminated intravascular coagulation (DIC) with an abnormal liver function, resulting in unfavorable outcomes. The aim of the present study was to clarify the correlation between liver function test results and DIC scores. Methods Twenty patients diagnosed with JSF between April 2010 and April 2014 were enrolled. Age, gender, disturbance of consciousness, body temperature, pulse rate, presence of diffuse erythema, eschar and swelling of lymph nodes, laboratory test results at the time of initial presentation such as blood cell count, C-reactive protein, liver function, renal function and blood coagulation and fibrinolysis, maximum Japanese Association for Acute Medicine (JAAM) DIC score during the course of JSF, treatment and the prognosis were retrospectively reviewed. Results The median age of the patients (8 men, 12 women) was 68.3 years. There were significant differences in the alkaline phosphatase (ALP) and rothrombin time international normalized ratio (PT-INR) between the DIC and non-DIC groups using Mann-Whitney's U test. A multiple logistic regression analysis showed that the ALP and blood urea nitrogen (BUN) levels at the time of initial presentation were independent predictors of the occurrence of DIC. Conclusion We should pay special attention to JSF patients showing high levels of ALP at the initial presentation, since such patients may have a higher likelihood of developing DIC over the course of JSF and unfavorable outcomes than those with lower levels.

Insufficient control of morning home blood pressure in Japanese patients with hypertension associated with diabetes mellitus.

UNLABELLED: Aims/Introduction: The combination of hypertension with diabetes mellitus (DM) has been recognized as a critical risk factor for cardiovascular disease (CVD). We investigated the blood pressure levels in hypertensive patients with DM (HDM patients) compared with those without DM (HnDM patients). Furthermore, we examined the effect of risk factors, including chronic kidney disease (CKD) and stroke, on the management of both office blood pressure (OBP) and morning home blood pressure (MHBP). MATERIALS AND METHODS: OBP and MHBP were evaluated in 1230 essential hypertensive patients in 30 institutions. Among them, 366 (30%) were complicated with DM. RESULTS: The ratio of masked hypertensives whose systolic OBP was <140 mmHg and systolic MHBP was more than 135 mmHg in HDM patients was significantly higher than that in HnDM patients (P < 0.02). HDM patients had significantly lower systolic and diastolic OBP and diastolic MHBP than HnDM patients (P < 0.05, respectively). However, systolic MHBP in HDM patients tended to be higher compared with HnDM patients (P = 0.0623). A stratified analysis showed that HDM patients with CKD or stroke had significantly higher systolic MHBP than others (P < 0.05, respectively). The adjusted odds ratio for morning hypertension defined by a systolic MHBP more than 135 mmHg was significantly higher in the HDM patients with CKD (1.98) compared with HnDM patients without CKD (reference). CONCLUSIONS: Diabetes, CKD and stroke are risk factors for MHBP. More intensive treatment is needed to achieve the thera-peutic goal for systolic MHBP in HDM patients, especially those who are complicated with CKD or stroke. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00056.x, 2010).

Olmesartan and temocapril prevented the development of hyperglycemia and the deterioration of pancreatic islet morphology in Otsuka-Long-Evans-Tokushima Fatty rats.

We investigated the impact of olmesartan and temocapril on pancreatic islet beta-cells during the development of diabetes mellitus using Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats. Four-week-old male OLETF rats were fed standard chow (untreated:n5), or chow containing either 0.005% olmesartan(n5) or 0.01% temocapril (n5) until being sacrificed at 35 weeks of age. Pancreas sections were double-stained with anti-insulin and anti-glucagon antibodies. The percent areas of beta-cells, alpha-cells and non-alpha-non-beta-cells were compared among groups. In untreated OLETF rats, the fasting plasma glucose (FPG) level was elevated at the 18th week and remained elevated until the 35th week. On the other hand, no significant elevation in FPG levels was observed in olmesartan- or temocapril-treated rats. Pancreatic islets from olmesartan-treated rats were significantly smaller in size as compared with those from untreated OLETF rats. Furthermore, the average area occupied by beta-cells as a fraction of the total area of an individual islet was significantly higher in olmesartan- or temocapril-treated rats than that in untreated OLETF rats. Olmesartan and temocapril both prevented the development of hyperglycemia, possibly through the prevention of islet beta-cell loss in spontaneously diabetic OLETF rats.

The MUSCAT study: a Multicenter PROBE Study Comparing the Effects of Angiotensin II Type-1 Receptor Blockers on Self-Monitored Home Blood Pressure in Patients with Morning Hypertension: study design and background characteristics.

Elevated morning home blood pressure (MHBP) has been reported to have a close relationship to cerebro-cardiovascular events and hypertensive target organ damages, and hence is regarded as a predictor of cardiovascular events. However, there is no evidence that lowering of MHBP can improve morbidity, mortality or target organ damage. In recent guidelines, angiotensin II type-1 receptor blockers (ARBs) are recommended as the first-choice drugs for antihypertensive therapy. Pharmacological characteristics differ among ARBs, and some are suggested to have greater efficacy in lowering MHBP than others. In preparation for the MUSCAT study, we surveyed both self-monitored MHBP and office blood pressure (OBP) in 1,234 patients with essential hypertension. Among them, 367 patients had diabetes mellitus (DM) and 229 suffered from chronic kidney disease (CKD). More than 64% (n=790) of patients had morning hypertension. In MUSCAT, we will investigate the different effects of four ARBs (losartan, candesartan, valsartan, and telmisartan) in patients with morning hypertension, with a focus on the drugs' MHBP-lowering efficiency. Secondly, we will evaluate the different actions of the four ARBs on cardiovascular surrogate markers, such as the brachial-ankle pulse wave velocity, high-sensitive C-reactive protein level, and urinary albumin excretion/creatinine ratio. Patients will be randomized into four arms, and given one of the four "sartans" once daily for 12 months. MHBPs and surrogate markers will be examined at baseline and after 1 year of follow-up. In the stratified analysis, we will determine the significance of MHBP reduction on cardiovascular risk management.

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.

Practical efficacy of telmisartan for decreasing morning home blood pressure and pulse wave velocity in patients with mild-to-moderate hypertension.

The current guideline-recommended blood pressure values are difficult to maintain in general practice, partly due to the lack of ideal anti-hypertensive agents. Since morning hypertension has a high correlation with cardiovascular events, expectations that telmisartan, a long-acting angiotensin-II type-1 receptor blocker (ARB), can improve cardiovascular mortality are high. In this study, the efficiency of telmisartan in reducing morning hypertension and pulse wave velocity (PWV) as a practical surrogate endpoint was investigated. Seventeen unsupervised and 7 untreated hypertensive patients were prescribed telmisartan 40 mg/day for 3 months. Medication already prescribed upon enrollment in this study was continued, with the exception of ARBs (all of which turned out to be losartan 50 mg/day), which were discontinued and replaced with telmisartan. Morning home blood pressure (MHBP), office blood pressure (OBP), and brachial-ankle PWV (baPWV) were investigated in a prospective fashion. A stratified analysis was performed regarding previous use (group L) or non-use (group N) of losartan. Over a 3-month period, telmisartan was found to significantly reduce both OBP (from 153+/-13/85+/-9 to 141+/-17/80+/-7 mmHg (p <0.01)) and MHBP (from 153+/-23/93+/-11 to 137+/-22/82+/-10 mmHg (p <0.001)). Surprisingly, 7 patients (70%) from group L achieved an OBP of less than 140/90 mmHg by simply changing their medication to telmisartan. Furthermore, baPWV fell significantly from 1,892+/-334 cm/s to 1,672+/-324 cm/s (p <0.01), which was greater than the change in baPWV estimated by OBP reduction. Here it must be mentioned that there were no significant differences between group L and group N in the courses of blood pressures and baPWV. In conclusion, telmisartan 40 mg/day was found to be effective for reducing MHBP and arterial wall stiffness in patients with mild-to-moderate hypertension, and thus may also be effective for improving cerebrocardiovascular mortality.

[Effect of angiotensin II receptor blocker on insulin signaling in skeletal muscle cells].

Impairment of insulin-dependent glucose uptake in skeletal muscles plays a major role in the pathogenesis of diabetes mellitus. Angiotensin converting-enzyme inhibitor (ACEI) has been demonstrated to improve insulin-sensitivity in diabetic patients, partly through the increase in peripheral blood flow mediated by either suppressed angiotensin II or elevated bradykinin. Recently, angiotensin II type-1 receptor blocker (ARB) has been shown to produce similar effects, postulating the importance of intracellular signaling cross-talk between angiotensin II and insulin. In this brief review, we focused on insulin receptor substrate-1(IRS-1) in skeletal muscle cells, and the significance of its serine(612)-phosphorylation was discussed.