Determinants of Left Ventricular Hypertrophy in Hypertensive Patients: Identification of High-Risk Patients by Metabolic,Vascular, and Inflammatory Risk Factors

Left ventricular hypertrophy (LVH) is recognized as an independent predictor of cardiovascular morbidity and mortality in hypertensive patients. Thus, it is critical to understand the mechanisms underlying the development of LVH for formulation screening and treatment strategies. This study was designed to determine the association between echographically determined LVH measures and markers of inflammation, neurohormonal activity, glomerular function, oxidative stress, insulin resistance, and vascular endothelial function. In this study, 129 hypertensive subjects were evaluated for lipids, glucose, HbA1C, insulin, homeostasis model assessment-insulin resistance, C-reactive protein (CRP), urinary microalbumin, homocysteine, aldosterone, renin, and endothelin. LVH parameters including interventricular septum thickness, posterior wall thickness (PWT), and left ventricular mass index (LVMI) were assessed echographically. Serum aldosterone levels were significantly positively associated with left ventricular mass (LVM) and marginally positively associated with LVMI and PWT. Both LVM and LVMI were significantly elevated in subjects with high versus normal serum aldosterone levels (p = 0.018 for LVM and p = 0.050 for LVMI). Serum endothelin was positively associated with LVM and LVMI. In multiple linear regression analysis, aldosterone remained a significant predictor of LVM (standardized β = 0.229, p = 0.024), and endothelin a marginally significant predictor of LVM (standardized β = 0.178, p = 0.077). Among serum lipids, high-density lipoprotein cholesterol only had a significant inverse association with LVM and PWT. Homocysteine as well as CRP were significantly positively associated with LVM and LVMI in females. This study found that aldosterone and endothelin levels are the most important independent determinants of LVH in hypertensive subjects. These markers may be useful to identify asymptomatic hypertensive subjects at risk for heart failure.     

Self-management training for children with reading problems: Effects on reading performance and sustained attention

Fifth-graders identified as poor readers were randomly assigned to a self-management or a modeling control condition. The self-management treatment consisted of a slightly modified version of Meichenbaum's (Meichenbaum & Goodman, 1971) self-instructional procedure, i.e., five sequential steps during which task-oriented verbalizations were gradually faded to covert speech. The modeling control condition resembled a tutorial session, with the instructor modeling self-management task-approach behaviors without prompting subjects to perform them. All subjects were exposed to the same materials, tasks, and trainers, who were kept blind regarding the purpose of the study. The results indicated that students receiving self-management training performed better than the control group on a reading task. Moreover, self-management subjects committed fewer errors and manifested greater inhibitory control over their behavior on a measure of sustained attention. A postexperimental transfer measure of children's teaching style of a peer who had not participated in the study furthermore showed that only the experimental subjects consistently employed varied aspects of the self-management program.This study was undertaken as part of a doctoral dissertation submitted at the University of California, Los Angeles. The author would like to thank Dr. Barbara Henker of the psychology department, UCLA, for her valuable guidance throughout the varied phases of the research project.     

Changes in brain catecholamine turnover and receptor sensitivity induced by social deprivation in rats

Catecholamine turnover was compared in two brain areas of rats housed under different social conditions. Rats reared in isolation for 6–8 weeks had a significantly lower noradrenaline turnover in the brainstem and lower noradrenaline and dopamine turnover in a brain segment comprising all other areas except the cerebellum, pineal gland, thalamus, and and subthalamus. In the open-field test, isolated rats were much more active than group-housed animals. Noradrenaline turnover increased in both brain areas of isolated rats but not in grouped animals after exposure to the open field. Hyperactivity was selectively reduced in isolated rats by chronic oral treatment with d-amphetamine, 5 mg/kg/24 h. It was also reduced 15 min after pretreatment with -methyl-p-tyrosine 200 mg/kg. It is suggested that a prolonged period of reduced noradrenaline release may sensitise postsynaptic receptors in isolated rats. Hyperactivity appears to be associated with an increase in transmitter release onto sensitised receptors.This study comprises part of a Ph. D. thesis by Z. Speiser to be submitted to Tel Aviv University     

Evaluation of the Nursing Outcomes Classification (NOC)--from theory to practice in Israel

A study was undertaken on the use of the Nursing Outcomes Classification (NOC) in different practice settings in Israel that included an analysis of problems that can arise in using NOC and a proposed solution. The results indicated four main problems with using the NOC in nursing practice: It is not possible to build from several indicators a weighted index for estimating patient outcomes; some of the indicators are not identical to the clinical guidelines; the grading scales depend largely on subjective judgment; and we question whether an evaluation scale of 5 grades is necessary for such numerical values as vital signs. We suggest dividing the NOC into three main categories (based on original values, objective values as suggested in the clinical guidelines, and values that require the development of quantitative indices) to enable better implementation.     

Estimated number of loci for autosomal recessive severe nerve deafness within the Israeli Jewish population,with implications for genetic counseling

Deafness occurs in about 1 per thousand live births, and at least 50% of congenital deafness is hereditary. The aim of this study was to examine the number of loci for recessively in herited severe nerve deafness of early onset within the Israeli population and to compare the results to those obtained in other populations. The Jewish population in Israel originates from many countries and may be divided into Sephardi, Eastern and Ashkenazi Jews, and the matings will be intraethnic or interethnic. Data were obtained on 133 deaf couples who lived in the Tel Aviv area, through the files of the Helen Keller Center. Causes of deafness in the spouses were studied and data on their children were obtained. Among 111 couples who had recessive or possibly recessive deafness and had at least 1 child, there were 12 with only deaf children and 5 with both deaf and hearing children. The number of loci for recessive deafness in the whole group was estimated at 8–9. Intraethnic and interethnic matings gave an estimate of 6.7 and 22.0 loci, respectively, which indicates that within populations fewer loci exist with recessive mutations for deafness than between populations. it could be shown that the sharing of loci between spouses decreased with increasing geographical distance of their origin. The results provide data for genetic counseling in Israel for deaf couples who have no children or have one hearing or one deaf child.     

Inhibitors that target protein kinases for the treatment of ovarian carcinoma

OBJECTIVE: Ovarian cancer is the leading cause of death from gynecologic malignancies in the United States. In an attempt to develop drugs that suppress ovarian cancer cells, we examined the effect of selective inhibitors of protein tyrosine kinases-tyrphostins, which are likely to play a role in ovarian cancer cells. STUDY DESIGN: We examined the cellular and biochemical effects of tyrphostins AG1478, PP2, AGL2592, and AG490 from four different families on the ovarian carcinoma cell line OV1063. RESULTS: We found that the AG1478, PP2, AGL2592, and AG490 tyrphostins suppressed cell proliferation and altered cell cycle distribution of the OV1063 cells in a dose- and time-dependent manner. Immunoblotting analysis indicated that AG1478 effectively inhibited epidermal growth factor receptor autophosphorylation, that AG490 decreased the level of Jak2 and phosphorylated Stat3, and that PP2 decreased the level of pp60Src protein. AGL2592 decreased the level of constitutive activated epidermal growth factor receptor and pStat3, but its molecular targets have not been identified completely. CONCLUSION: The growth-arresting properties of these tyrphostins identify them as possible candidates for signal transduction therapy.     

AF150(S) and AF267B: M1 muscarinic agonists as innovative therapies for Alzheimer's disease

The M1 muscarinic agonists AF102B (Cevimeline, EVOXACTM: prescribed in USA and Japan for Sjogren's Syndrome), AF150(S) and AF267B--1) are neurotrophic and synergistic with neurotrophins such as nerve growth factor and epidermal growth factor; 2) elevate the non-amyloidogenic amyloid precursor protein (alpha-APPs) in vitro and decrease beta-amyloid (A beta) levels in vitro and in vivo; and 3) inhibit A beta- and oxidative-stress-induced cell death and apoptosis in PC12 cells transfected with the M1 muscarinic receptor. These effects can be combined with the beneficial effects of these compounds on some other major hallmarks of Alzheimer's disease (AD) (e.g. tau hyperphosphorylation and paired helical filaments [PHF]; and loss of cholinergic function conducive to cognitive impairments.) These drugs restored cognitive impairments in several animal models for AD, mimicking different aspects of AD, with a high safety margin (e.g. AF150[S] >1500 and AF267B >4500). Notably, these compounds show a high bioavailability and a remarkable preference for the brain vs. plasma following p.o. administration. In mice with small hippocampi, unlike rivastigmine and nicotine, AF150(S) and AF267B restored cognitive impairments also on escape latency in a Morris water maze paradigm in reversal learning. Furthermore, in aged and cognitively impaired microcebes (a natural animal model that mimics AD pathology and cognitive impairments), prolonged treatment with AF150(S) restored cognitive and behavioral impairments and decreased tau hyperphosphorylation, PHF and astrogliosis. Our M1 agonists, alone or in polypharmacy, may present a unique therapy in AD due to their beneficial effects on major hallmarks of AD.