Cardiovascular risk factors and homocysteine in epilepsy

Epidemiological studies have found the risk for heart disease and stroke are increased in persons with epilepsy. Anti-epileptic drugs (AEDs) have varying effects on serum lipids and homocysteine-an independent risk factor for coronary disease. The prevalence of cardiovascular risk factors (high cholesterol, hypertension, diabetes, obesity and smoking) and homocysteine were investigated in a multiethnic epilepsy population. Data included demographics, clinical factors, lab assessments and supplementation patterns. Mean age was 45 years (71 males and 94 females)-75 were African American, 27 Latino and 60 Caucasian. Fifty-two percent of participants had two or more cardiovascular risk factors when compared with rates for the general population of 28%. The Framingham risk score (FRS) assessment was also used to compare risk levels. Twenty-nine percent of men and 1% of women had a FRS indicating >5% level of risk, only 7% had a FRS>10%. Cardiovascular screening and primary preventative recommendations based on the American Heart Association and supplementation should be suggested for the adult epilepsy population when appropriate.     

Development of a monoclonal antibody binding okadaic acid and dinophysistoxins-1, -2 in proportion to their toxicity equivalence factors

Okadaic acid (OA) and structurally related toxins dinophysistoxin-1 (DTX-1), and DTX-2, are lipophilic marine biotoxins. The current reference method for the analysis of these toxins is the mouse bioassay (MBA). This method is under increasing criticism both from an ethical point of view and because of its limited sensitivity and specificity. Alternative replacement methods must be rapid, robust, cost effective, specific and sensitive. Although published immuno-based detection techniques have good sensitivities, they are restricted in their use because of their inability to: (i) detect all of the OA toxins that contribute to contamination; and (ii) factor in the relative toxicities of each contaminant. Monoclonal antibodies (MAbs) were produced to OA and an automated biosensor screening assay developed and compared with ELISA techniques. The screening assay was designed to increase the probability of identifying a MAb capable of detecting all OA toxins. The result was the generation of a unique MAb which not only cross-reacted with both DTX-1 and DTX-2 but had a cross-reactivity profile in buffer that reflected exactly the intrinsic toxic potency of the OA group of toxins. Preliminary matrix studies reflected these results. This antibody is an excellent candidate for the development of a range of functional immunochemical-based detection assays for this group of toxins.     

Thrombosis in myeloproliferative disorders: prevalence, prognostic factors, and the role of leukocytes and JAK2V617F

An underlying myeloproliferative disorder (MPD), especially polycythemia vera (PV) or essential thrombocythemia (ET), is a risk factor for thrombosis. Considering large selected studies, prevalence rates for major thrombosis, at time of diagnosis, range from approximately 34 to 39% for PV and 10 to 29% for ET; the corresponding figures for thrombosis at follow-up are approximately 8 to 19% for PV and 8 to 31% for ET. In all instances, arterial events were more frequent than venous events. In both PV and ET, advanced age and history of thrombosis are independent predictors of recurrent thrombosis. In addition, leukocytosis, but not thrombocytosis, has been identified as a potential risk factor for thrombosis in both diseases. The particular observation is consistent with the laboratory demonstration, in these disorders, of increased number of activated granulocytes and granulocyte-platelet aggregates, upregulation of platelet P-selectin and tissue factor expression by granulocytes, and the antithrombotic value of hydroxyurea therapy. Most recently, a JAK2 gain-of-function mutation ( JAK2V617F) was described in virtually all patients with PV and approximately 50% of those with ET. Whether the presence of this specific mutation or its allele burden modifies the risk of thrombosis in patients with MPDs currently is under investigation.     

Food omega-3 fatty acid intake of individuals (total, linolenic acid, long-chain) and their blood pressure: INTERMAP study

Findings from short-term randomized trials indicate that dietary supplements of omega-3 polyunsaturated fatty acids (PFA) lower blood pressure of hypertensive persons, but effect size in nonhypertensive individuals is small and nonsignificant. Data are lacking on food omega-3 PFA and blood pressure in general populations. The International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) is an international cross-sectional epidemiologic study of 4680 men and women ages 40 to 59 from 17 population-based samples in China, Japan, United Kingdom, and United States. We report associations of food omega-3 PFA intake (total, linolenic acid, long-chain) of individuals with blood pressure. Systolic and diastolic blood pressure were measured 8 times at 4 visits. With several models to control for possible confounders (dietary, other), linear regression analyses showed inverse relationship of total omega-3 PFA from food (percent kilocalories, from four 24-hour dietary recalls) to systolic and diastolic blood pressures. With adjustment for 17 variables, estimated systolic blood pressure/diastolic blood pressure differences with 2 standard deviation higher (0.67% kcal) omega-3 PFA were -0.55/-0.57 mm Hg (Z-score -1.33, -2.00); for 2238 persons without medical or dietary intervention, -1.01/-0.98 mm Hg (Z -1.63, -2.25); for 2038 nonhypertensive persons from this sub-cohort, -0.91/-0.92 mm Hg (Z -1.80, -2.38). For linolenic acid (largely from vegetable foods), blood pressure differences were similar, eg, for the 2238 "nonintervened" individuals, -0.97/-0.87 mm Hg (Z -1.52, -1.95); blood pressure differences were -0.32/-0.45 mm Hg for long-chain omega-3 PFA (largely from fish). In summary, food omega-3 PFA intake related inversely to blood pressure, including in nonhypertensive persons, with small estimated effect size. Food omega-3 PFA may contribute to prevention and control of adverse blood pressure levels.     

Epstein-Barr virus and virus human protein interaction maps

A comprehensive mapping of interactions among Epstein-Barr virus (EBV) proteins and interactions of EBV proteins with human proteins should provide specific hypotheses and a broad perspective on EBV strategies for replication and persistence. Interactions of EBV proteins with each other and with human proteins were assessed by using a stringent high-throughput yeast two-hybrid system. Overall, 43 interactions between EBV proteins and 173 interactions between EBV and human proteins were identified. EBV-EBV and EBV-human protein interaction, or "interactome" maps provided a framework for hypotheses of protein function. For example, LF2, an EBV protein of unknown function interacted with the EBV immediate early R transactivator (Rta) and was found to inhibit Rta transactivation. From a broader perspective, EBV genes can be divided into two evolutionary classes, "core" genes, which are conserved across all herpesviruses and subfamily specific, or "noncore" genes. Our EBV-EBV interactome map is enriched for interactions among proteins in the same evolutionary class. Furthermore, human proteins targeted by EBV proteins were enriched for highly connected or "hub" proteins and for proteins with relatively short paths to all other proteins in the human interactome network. Targeting of hubs might be an efficient mechanism for EBV reorganization of cellular processes.     

Strategies for Coping in a Complex World: Adherence Behavior Among Older Adults with Chronic Illness

Background Increasing numbers of medicines increase nonadherence. Little is known about how older adults manage multiple medicines for multiple illnesses. Objectives To explore how older adults with multiple illnesses make choices about medicines. Design Semistructured interviews with older adults taking several medications. Accounts of respondents’ medicine-taking behavior were collected. Participants Twenty community-dwelling seniors with health insurance, in Eastern Massachusetts, aged 67–90, (4–12 medicines, 3–9 comorbidities). Approach Qualitative analysis using constant comparison to explain real choices made about medicines in the past (“historical”) and hypothetical (“future”) choices. Results Respondents reported both past (“historical”) choices and hypothetical (“future”) choices between medicines. Although people discussed effectiveness and future risk of the disease when prompted to prioritize their medicines (future choices), key factors leading to nonadherence (historical choices) were costs and side effects. Specific choices were generally dominated by 1 factor, and respondents rarely reported making explicit trade-offs between different factors. Factors affecting 1 choice were not necessarily the same as those affecting another choice in the same person. There was no evidence of “adherent” personalities. Conclusion Prescribing a new medicine, a change in provider or copayment can provoke new choices about both new and existing medications in older adults with multiple morbidities. This paper was presented as: (1) Towards an understanding of non-adherence in the elderly with multiple illnesses, at the RW Johnson Seminar Series, School of Medicine, University of Michigan, Ann Arbor, MI, USA, May 2005; (2) Barriers to medicines taking in vulnerable populations, at the Second Annual Symposium of the HMS Fellowship in Pharmaceutical Policy Research, Harvard Medical School, Boston, MA, USA, June 2005; (3) Barriers to medicines taking in vulnerable populations, at the Harkness Fellows in Health Policy Reporting Seminar, Boston, MA, USA, June 2005; (4) Elliott RA, Ross-Degnan D, Adams AS, Safran DG, Soumerai SB. Towards an understanding of medication non-adherence in the elderly with multiple illnesses. Society of Medical Decision Making, Birmingham June 2006. [oral]