Elevated Diastolic,But Not Systolic,Blood Pressure Measured in the Emergency Department Predicts Future Development of Hypertension in Normotensive Individuals

Elevated blood pressure (BP) is reported in many individuals without hypertension presenting to the emergency department (ED). Whether this condition represents a transient state or is predictive for the development of future hypertension is unknown. This observational prospective study investigated patients admitted to an ED without a diagnosis of hypertension in whom BP values were ≥140/90 mm Hg. The primary outcome was development of hypertension during follow‐up. Overall, 195 patients were recruited and at the end of follow‐up (average 30.14±15.96 months), 142 patients were diagnosed with hypertension (73%). The mean age (50±12.25 vs 48.31±13.9, P=.419) and sex distribution (78 men/64 women vs 24 men/20 women, respectively; P=.148) were similar in both groups. There were significant differences in systolic and diastolic BP between those who developed hypertension on follow‐up and those who did not (177.6 mm Hg±22.6/106.1 mm Hg±16.9 vs 168.6 mm Hg±18/95.2 mm Hg±12.2; P=.011 for systolic BP, P<.001 for diastolic BP). In multivariate analysis the only significant predictive factor for the development of hypertension was diastolic hypertension recorded in the ED (P=.03). Elevated diastolic, but not systolic, BP among patients presenting to the ED is associated with future development of hypertension in previously normotensive individuals.     

Basic secretagogues activate protein tyrosine phosphorylation and release of arachidonic acid in mast cells via a novel protein kinase C and phosphatidylinositol 3-kinase-dependent mechanism

Mast cells play a central role in inflammatory and immediate-type allergic reactions. These granulated cells release by a process of regulated exocytosis a variety of biologically active substances which are either preformed (e. g. histamine), or synthesized de novo following activation [e. g. metabolites of arachidonic acid (AA) and multifunctional cytokines]. Exocytosis in mast cells is activated either in response to aggregation of the receptors for immunoglobulin E (FcϵRI) or by the direct activation of pertussis toxin-sensitive G-proteins by a class of receptor mimetic agents, collectively known as basic secretagogues of mast cells. In the present study we show that compound 48/80 (c48/80), a synthetic member of the class of basic secretagogues, stimulates protein tyrosine phosphorylation of a number of as yet unidentified cellular substrates.These phosphorylations were inhibited by the tyrphostin AG-18, by the phosphatidylinositol 3-kinase inhibitor wortmannin and by the protein kinase C inhibitors K252a and GF109203X. These inhibitors also inhibited the release of AA induced by c48/80 but had no effect on exocytosis. Taken together, our findings suggest that basic secretagogues induce protein tyrosine phosphorylation as part of their parallel multiple signaling pathways which are presumably mediated by more than one G-protein. Both protein kinase C and phosphatidylinositol 3-kinase serve as intermediates in this signaling pathway. The protein tyrosine kinase signaling pathway, which mediates the activation of AA release, does not contribute to secretion of the preformed mediators such as histamine, but it might largely contribute to the de novo production of inflammatory mediators like leukotrienes and prostaglandins.     

Case series of perimenopausal women with insomnia treated with mirtazapine followed by prolonged-release melatonin add-on and monotherapy

Objectives  

The sedating antidepressant mirtazapine is used off label for insomnia in perimenopausal women. Despite its apparent efficacy, mirtazapine causes significant increases in appetite and weight gain. Prolonged-release melatonin (PRM) is approved for primary insomnia in patients aged 55 years and older. A clinical experience with PRM add-on to mirtazapine in facilitating mirtazapine withdrawal while maintaining improved sleep quality and abrogating weight gain in perimenopausal women with insomnia is described.     

Focal liver necrosis appears early after partial hepatectomy and is dependent on T cells and antigen delivery from the gut

Introduction: Progressive liver failure may develop following removal of a large part of the liver or transplantation of a small for size liver graft. The pathophysiology of this clinical syndrome is only partially understood. Methods: We assessed liver damage and hepatocyte 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation following partial hepatectomy (PH) in C57BL/6, BALB/C and immune‐deficient mice. Hepatic lymphocyte subpopulations were characterized. Lipopolysaccharide (LPS) treatment and bowel decontamination determined the role of gut antigens. Results: Discrete, round necrotic lesions were observed as early as 2 h following 70%, but not 30% PH. In immune competent mice the extent of hepatocyte necrosis inversely correlated with BrdU incorporation. T, natural killer and natural killer T cells were recruited to the liver early after PH; however, only T‐cell depletion abrogated hepatic necrosis. Hepatic injury was significantly reduced in non‐obese diabetic/severe combined immunodeficient mice undergoing PH, while BrdU incorporation was not affected. Liver injury was augmented by LPS injection and reduced by gut decontamination. Conclusions: A distinct pattern of early focal hepatic necrosis is observed following extensive PH in mice. T cells infiltrating the liver immediately after PH and gut‐derived antigens are indispensable for the observed liver necrosis and may thus provide therapeutic targets to ameliorate liver damage following PH.     

Effects of age-dependent membrane transport changes on the homeostasis of senescent human red blood cells

Little is known about age-related changes in red blood cell (RBC) membrane transport and homeostasis. We investigated first whether the known large variation in plasma membrane Ca(2+) (PMCA) pump activity was correlated with RBC age. Glycated hemoglobin, Hb A1c, was used as a reliable age marker for normal RBCs. We found an inverse correlation between PMCA strength and Hb A1c content, indicating that PMCA activity declines monotonically with RBC age. The previously described subpopulation of high-Na(+), low-density RBCs had the highest Hb A1c levels, suggesting it represents a late homeostatic condition of senescent RBCs. Thus, the normal densification process of RBCs with age must undergo late reversal, requiring a membrane permeability increase with net NaCl gain exceeding KCl loss. Activation of a nonselective cation channel, Pcat, was considered the key link in this density reversal. Investigation of Pcat properties showed that its most powerful activator was increased intracellular Ca(2+). Pcat was comparably selective to Na(+), K(+), choline, and N-methyl-D-glucamine, indicating a fairly large, poorly selective cation permeability pathway. Based on these observations, a working hypothesis is proposed to explain the mechanism of progressive RBC densification with age and of the late reversal to a low-density condition with altered ionic gradients.     

Helena Kagan (1889-1978): the first paediatrician in Israel

In the Spring of 1914 Helena Kagan, a young 25-year-old physician, settled in Jerusalem. She opened a clinic at her home and became the first paediatrician in the country. She founded institutions to improve the health of Jerusalem children and engaged in extensive public activity on behalf of the Jerusalem community.     

BNP in septic patients without systolic myocardial dysfunction

BACKGROUND: We tested our hypothesis that serum BNP levels rise in sepsis and septic shock patients as a result of an inflammatory state and not only because of left ventricular dysfunction. METHODS: Twenty-one patients with sepsis or septic shock were enrolled in the study. Echocardiography was performed in every patient on admission and at discharge. Laboratory data were evaluated on admission, during hospitalization, and at discharge. Serum IL-1beta, IL-6, TNFalpha, and BNP concentrations were determined. RESULTS: BNP values on admission (r=0.47, p=0.03), during hospitalization (r=0.64, p=0.014), and on the day of discharge (r=0.54, p=0.015) were all positively correlated with CRP values. Mean BNP (r=0.07, p=0.006) and BNP level at discharge (r=0.68, p=0.001) were also positively associated with IL-1 at discharge. Mean CRP (17.7 mg/dL+/-1.5 vs. 9.2 mg/dL+/-3.6, p=0.002), IL-6 (46.6 pg/mL+/-2.2 vs. 25.6 pg/mL+/-16.3, p=0.003), and SAPS II levels (41.3+/-4.7 vs. 33.9+/-6.5 p=0.01) were also higher in patients who died versus those who survived. No difference in BNP levels was recorded in subjects who died versus those who survived. There was no clinical or echocardiographic evidence of left ventricular systolic dysfunction (mean EF% on admission 55.1+/-21.7 vs. 61.3+/-8.6 on discharge, p=0.123). Serum BNP levels at discharge were inversely associated with EF values on admission (r=-0.475, p=0.046) and positively associated with E/A ratio on admission (r=0.565, p=0.028). No association was found between BNP values and death. CONCLUSION: BNP is positively correlated with CRP levels in septic patients without clinical or echocardiographic evidence of systolic dysfunction. No association was found between death and BNP values. It seems that, in septic patients, BNP is less accurate as a measure of ventricular dysfunction.