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Self-serving (hedonic) bias Hopelessness Theory of Depression the use of attribution concepts medications ending in zole buy leflunomide 20 mg on line, including the notion of attributional style medicine hollywood undead order leflunomide, in understanding learned helplessness and depression led to conventional medicine 20mg leflunomide free shipping the formulation that the presence of a pessimistic attributional style increased the risk that an individual would experience helplessness, hopelessness and depression (Abramson et al. This attribution dimension was later incorporated as a key component of the hopelessness theory of depression (Abramson et al. This model predicts that an individual is at risk for hopelessness depression to the extent that negative events are attributed to internal, stable and global causes, and that these causes are perceived as both likely to prompt other negative consequences and to be reflective of deficiencies or shortcomings of self. Further, cognitive vulnerability to hopelessness depression is conceptualized as a function of individual differences in attributional style as well as the propensity to infer negative consequences and negative self-evaluation in response to adverse events (Gotlib and Abramson, 1999). Specifically, the self-serving bias reflects a wish to present oneself in the best possible light. People tend to extend this attribution bias to important others in their interpersonal sphere. Multiple explanations have been offered in the literature regarding the causal underpinnings of these attribution biases (Forsterling, 2001). Attributions in Health and Illness Given that attribution processes tend to be activated by negative, unanticipated, or ambiguous events, it is logical to assume that attribution theory would have a useful role in conceptualizing how people come to understand the causes of their illness as well as processes of stress and coping with illness (Amirkhan, 1990; Salovey et al. Empirical evidence supports this view, as exemplified in a recent meta-analytic study that suggested that attributions influence illness-related coping and adjustment (Roesch and Weiner, 2001). However, associations between specific attributions and illness should not be interpreted to mean that certain attribution patterns cause illness, but rather that they may be among a complex set of factors affecting responses to illness. It is clear that causal attributions are important in facilitating health promotion and positive health practices (Rodin and Salovey, 1989; Salovey et al. To the extent possible, treatment interventions with medically ill persons should incorporate a focus upon enhancing the individual perceptions of control over health and treatment regimens with the aim of increasing adherence to medical regimens and improving adjustment to medical procedures and conditions. Existing research also underscores Person Perception and Implicit Personality Theories Person perception, also referred to as social perception, pertains to the ways in which people formulate impressions of others (Leyens and Fiske, 1994). Social psychologists have long suggested that people formulate implicit personality theories that consist of general beliefs about human characteristics and patterns of covariation among personality traits (Schneider, 1973). These knowledge systems facilitate rapid formation of inferences about the enduring personality qualities of other people in everyday life by using assumptions about interrelationships among dispositional qualities to draw conclusions about observed behavior. More recently, schema concepts in social cognition have been investigated in order to specify cognitive processes through which individuals organize and represent coherent and meaningful impressions of others (Leyens and Fiske, 1994). These person perception variables affect interaction styles between physicians and their patients which, in turn, may influence the nature and quality of medical care. Person perception has clinical relevance for the cognitive interpretation of interpersonal situations. Thus, while person perception research has demonstrated a normative tendency to make rapid evaluations of others and interpersonal situations based on limited information, this process is apt to become problematic when cognitive distortions are operative. For example, the depressed person with low self-esteem and a pessimistic attributional style who, based on a few experiences of being criticized, perceives others as judgmental in virtually every interpersonal interaction is overgeneralizing based upon limited data. Implicit personality theories and schemas in social cognition are clinically applicable to understanding chronically maladaptive person perception processes. This may have particular relevance for the clinical understanding of personality disorders. For example, the patient with paranoid personality disorder may hold a pervasive view of others as potentially attacking, blaming and controlling (Benjamin, 1996). The patient with borderline personality disorder may perceive others as simultaneously rejecting, abandoning and needing dependent others (Benjamin, 1996). To address these maladaptive implicit personality theories, schemas and associated interaction patterns, effective psychotherapy helps patients identify dysfunctional person perceptions, develop an affective and cognitive awareness of the etiology of these beliefs and the functions they serve, and form more adaptive schemas of self in relation to others (Benjamin, 1996). Individual attitudes consist of three elements: cognitive (beliefs about attitude objects), affective (emotions elicited by attitude objects) and behavioral (action intentions or overt behavior directed toward attitude objects). Additionally, individual attitudes may be associatively or logically linked to form broader inter-attitudinal structures consisting of two or more attitudes (Eagly and Chaiken, 1998). Fundamentally, attitudes serve an important adaptive function by virtue of their evaluative properties involving distinctions of good stimuli presumed to enhance well-being from bad stimuli that could endanger well-being (Eagly and Chaiken, 1998). Attitude Theories Attitude theory and research has a rich history as one of the great areas of inquiry within social psychology (Eagly and Chaiken, 1998; Petty and Wegener, 1998).
Recently treatment kennel cough buy leflunomide 10 mg, the field has greatly expanded and now includes detailed examinations of the natural history of psychiatric disorders treatment shingles buy leflunomide amex, genetic epidemiology medicine 666 colds discount 10 mg leflunomide mastercard, the relationships between physical and mental disorders, and studies of the use and outcomes of mental health treatments. This expansion has required significant advances and developments in psychiatric epidemiologic methods (Tsuang and Tohen, 2002). Important characteristics that distinguish psychiatric epidemiological research from other clinical investigations are the inclusion of representative samples and the application of systematic methods for determining diagnosis or outcome. The specific type of sample and choice of mental health measure depend on the goal of the study. For studies aimed at establishing prevalence and incidence rates, the population-based survey is the optimal method. Complex sampling procedures have been developed to ensure random selection for both single-stage and two-stage studies. For studies of rare disorders, identified patients are usually ascertained from registries or a representative set of psychiatric treatment facilities. However, because only a minority of individuals with diagnosable disorders are ever treated for psychiatric problems within the mental health care system (Regier et al. The development of structured diagnostic interview schedules tailored to clear operationalized diagnostic criteria was the crucial element underlying the recent progress in psychiatric epidemiology. As a result of the development of structured diagnostic interview schedules, the need to establish the prevalence of specific disorders was finally realized, at least within the limits of our current ability to operationalize mental disorders and within the constraints inherent in interview data (Fennig and Bromet, 1992). Estimates suggest that approximately 12% of children (Institute of Medicine, 1989) and 15% of adults (Regier et al. More precise estimates will be possible as more sensitive diagnostic tools become available. Because the ultimate goal of epidemiological research is to understand the cause of disease and prevent its occurrence, epidemiology is the backbone of public health. To make such advances, investigators have had to overcome formidable problems that are unique to the study of psychiatric disorders. Foremost among their achievements has been the development of the ability to define mental disorders reliably and efficiently. This accomplishment has in turn allowed investigators to conduct descriptive analyses that have yielded much-needed estimates of the incidence, prevalence, age at onset, and frequency of recurrence of mental disorders. The ability to accurately categorize cases and noncases has also been essential for allowing psychiatric epidemiologists to progress from simple descriptive work establishing rates to analytical research aimed at identifying risk factors, as well as biological and psychosocial variables that modify the effects of these risk factors. Examples of promising areas in which there has been significant research activity recently include investigations of the genetic bases for psychiatric disorders (Risch and Merikangas, 1990) and the modification of risk by environmental exposures, especially in the prenatal period (Neugebauer et al. Whereas traditional epidemiology has largely been concerned with the occurrence and causes of disease, clinical epidemiology has emerged as a closely related discipline which seeks to identify the occurrence and determinants of clinical outcomes from illnesses (Weiss, 1985; Sackett et al. Clinical epidemiologic studies employ the same principles and methods of population-based epidemiology, but are usually conducted among clinical samples. Other examples include two countywide longitudinal studies of first-admission psychosis (Beiser et al. Psychopharmacoepidemiology has been an especially fast growing component of clinical epidemiologic inquiry (Wang et al. Clinical epidemiologic research has also begun to evaluate the economic costs associated with mental disorders, both the direct costs for provision of mental health services as well as the indirect costs to society, secondary to the disability caused disorders. For example, major depression was the single most burdensome disease in the world among individuals under 45 years of age. Another closely related area of inquiry is that of mental health services research. This discipline investigates the patterns of utilization of mental health services, unmet needs for treatment, barriers to help seeking, the appropriateness and quality of treatments, and premature dropout from treatment (Kessler et al. The accumulation of information on risk factors for mental disorders, their outcomes, and treatment has in turn led to another important line of inquiry in psychiatric epidemiology, namely, interventional research. In addition to efficacy trials of psychiatric treatments conducted under rigorously controlled conditions (Tohen et al. Finally, the proliferation of effective but costly interventions, coupled with growing constraints on health care budgets, have also made it imperative to study not only the effectiveness of interventions but also their cost-effectiveness and cost-benefits. For this reason, economic analyses now frequently accompany efficacy and effectiveness trials of interventions (Schoenbaum et al. However, when attrition occurs, the cumulative incidence rate is a less desirable measure.
A powerful reactivator of alkyl phosphate-inhibited acetylcholinesterase medicine hat news generic leflunomide 10 mg with amex, Biochim administering medications 7th edition answers buy leflunomide with american express. Reactivation kinetics of acetylcholinesterase from different species inhibited by highly toxic organophosphates medicine zoloft discount 20mg leflunomide amex, Arch. Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes, Biochem. Evaluation of oxime efficacy in nerve agent poisoning: development of a kinetic-based dynamic model, Toxicol. Bioscavengers: 8 Nerve AgentDevelopment of Progress in a New Mode of Protection against Organophosphorus Exposure David E. To overcome these disadvantages, the concept of using a bioscavenger has emerged as a new approach to reduce the in vivo toxicity of chemical warfare nerve agents. Bioscavengers fall into two broad categories, stoichiometric, that is, proteins that bind and detoxify a poison in some fixed molecular ratio, and catalytic, that is, proteins that can cause the breakdown of a molecule of a poison, regenerate, and then repeat the process until all of the poison molecules have been destroyed. Studies with equine or human butyrylcholinesterase or fetal bovine serum acetylcholinesterase showed that none of these scavengers elicited behavioral side effects the opinion or assertions contained herein are the private views of the authors and are not to be constructed as reflecting the view of the Department of the Army or the Department of Defense. These results were in stark contrast to the prolonged, up to 14 days, behavioral incapacitation experienced by animals that were pretreated with pyridostigmine and received the same dose of nerve agent followed by the standard atropine and oxime therapy with or without diazepam. Although several challenges still remain to be met before bioscavengers could augment or replace the current therapeutic regimes for nerve agent intoxication, the results to date offer impressive evidence for the value of this approach as the next generation of pharmaceuticals to afford protection against nerve agent poisoning with a virtual absence of behavioral side effects. This inhibition leads to an increase in the concentration of acetylcholine in the cholinergic synapses of both the peripheral and central nervous systems. Because numerous lines of evidence indicate that the sister enzyme butyrylcholinesterase (BuChE, E. The physiological consequences of elevated acetylcholine include alterations in the function of the respiratory center (de Candole et al. A sufficiently high level of acetylcholine or a sufficiently rapid increase in acetylcholine concentration precipitates a cholinergic crisis, resulting in dimming of vision, headache, shortness of breath, muscle weakness, and seizures. In the extreme, organophosphorus intoxication can be a life-threatening event, with death usually resulting from respiratory failure. This is often accompanied by secondary cardiovascular components, including hypotension, cardiac slowing, and arrhythmias (Taylor, 2001a, 2001b). Furthermore, it appears that greater than marginal improvement of these pharmacological approaches will be difficult because stronger drugs or higher doses of currently fielded drugs are likely to produce unacceptable performance decrements by themselves (Dunn and Sidell, 1989; Castro et al. The ineffectiveness of therapeutically administered oxime as a treatment for exposure to some nerve agents explains the continued research efforts aimed at alternative approaches to protection (Dunn and Sidell, 1989). To avoid the onset of a toxic insult, recent efforts have focused on identifying proteins that can act as biological scavengers of organophosphorus compounds and can remain stable in circulation for long periods of time. The concept of using a protein that can react with a nerve agent, either on a one to one basis (stoichiometrically) or with the capability to breakdown the nerve agent (catalytically) to protect against the toxic effects of those compounds is not new. This approach avoids the side effects and the requirement for rapid administration associated with current antidotes (Erdmann et al. Ideally, the scavenger would enjoy a long residence time in the bloodstream, would be biologically innocuous in the absence of nerve agent, and would not present an antigenic challenge to the immune system. For these reasons, a formal program to identify candidate bioscavengers was started in 1993 by the U. Army Medical Research Materiel Command, and it has focused on enzymes of mammalian (particularly human) origin. In the former category are naturally occurring human proteins that bind or react with nerve agents, including enzymes such as cholinesterases (ChEs) and carboxylesterases (CaEs). Each of these stoichiometric scavengers has the capacity to bind one molecule of nerve agent per molecule of protein scavenger. Although this approach has been proven to be effective in laboratory animals, it has the disadvantage that the extent of protection is directly proportional to the concentration of unreacted, active scavenger in the bloodstream at the time of nerve agent exposure. It might be possible to mitigate the need for large amounts of scavenger by also administering, either prophylactically or immediately after exposure, a currently fielded oxime. Oxime treatment might allow the continual reactivation of the bioscavenger in vivo, in effect converting the stoichiometric scavenger into a pseudocatalytic one. The ability to engineer site-specific amino acid mutations into naturally occurring scavenger enzymes can allow investigators to alter the binding and catalytic activities of these enzymes.
As described in a comprehensive meta-analysis of over 180 studies with more than 40 immune measures medicine mountain scout ranch discount leflunomide online visa, many immunological changes reliably occur in patients with major depressive disorder (Zorrilla et al medicine 627 best buy for leflunomide. The experience of depression on the immune system is moderated by age medications qid safe leflunomide 10mg, sex, socioeconomic status, life stress, physical activity, and sleep. For these efferent pathways, multiple aspects of the immune system are altered with evidence of immune suppression. In turn, such immune changes have implications for infectious disease risk and the occurrence of inflammatory disorders. Clinical moderating factors It has been recognized that several clinical variables may influence immune measures and moderate the association between depression and changes in enumerative and functional measures of immunity, including age, gender, body mass, life stress, smoking and other psychiatric comorbidity (Stein et al. For example, older adults show declines in cellular immunity, and it appears that the presence of depression exacerbates age-related immune alterations (Schleifer et al. Third, in healthy adult depressed patients, adiposity and great body mass partially mediate the increase of inflammatory markers (see below) (Miller et al. Finally, specific diagnostic comorbidity such as anxiety disorder and alcohol dependence (Irwin et al. Given emerging data that sympathetic effector mechanisms have potent suppressive effects on natural and cellular immune responses in animal models, attention began to focus on the role of sympathetic neurotransmitters in contributing to the alterations of immune function in depression. At rest and in response to acute physical and/or psychological challenge, depressed patients show elevated levels of circulating catecholamines and neuropeptide Y (Irwin et al. Sympathetic nerve terminals are juxtaposed with immune cells in organs where immune system cells develop and respond to pathogens (Friedman and Irwin, 1997; Sanders and Straub, 2002). Cortisol exerts diverse effects on a wide variety of physiological systems, and also coordinates the action of various cells involved in an immune response by altering the production of cytokines or immune messengers. Similar to sympathetic activation, cortisol can suppress the cellular immune response critical in defending the body against viral infections. Cortisol can also prompt some immune cells to move out from circulating blood into lymphoid organs or peripheral tissues such as the skin (Dhabhar et al. For example, in depressed patients, decreased lymphocyte responses to mitogens are associated neither with dexamethasone nonsuppression (Kronfol and House, 1985) nor with increased excretion rates of urinary free cortisol (Kronfol et al. Of note, however, as indicated below, dexamethasone nonsuppression has been associated with evidence of increased activation of innate immune responses. With in vivo challenge by means of delayed-type hypersensitivity responses, it was reported that depressed patients were less responsive to a panel of antigenic challenges. Moreover, memory T-cell function in response to a specific viral pathogen was lower in depressed patients as compared to controls (Irwin et al. In other studies, psychological stress was reported to induce a marked decline in specific immune responses to immunization against viral infections (Vedhara et al. Behavioral mechanisms In addition to the biological mediators of immune changes in depression, several behavioral factors associated with depression appear to contribute to immune dysfunction. Conversely, exercise has been shown to have potent salutary effects on immune measures. In the meta-analysis from Herbert and Cohen (1993), melancholic depression correlated with greater impairments of cellular immunity which may be due, at least in part, to an increased predominance of neurovegetative symptoms. Stimulated cytokine production In animal models, stress was found to alter the expression of proinflammatory, anti-inflammatory, and T-helper 1 versus T-helper 2 (Th1/Th2) cytokines that were involved in initiating and coordinating immune responses to infectious challenge (Moynihan et al. In addition, peripheral blood mononuclear cells of nonmelancholic depressed patients showed a greater stimulated capacity to produce interleukin-1b and interleukin-1 receptor antagonist as compared to responses from controls and melancholic depressed patients (Kaestner et al. Given that insomnia is one of the most common complaints of depressed subjects, investigators explored whether sleep disturbances were associated with immune alterations in depression. Likewise, in studies that evaluated sleep using polysomnography, decreases of total sleep as well as sleep efficiency were shown to correlate with declines in natural and cellular immune function among depressed patients (Irwin et al. Inflammation and circulating levels of inflammatory markers In patients with inflammatory disorders such as rheumatoid arthritis (Zautra et al. Although early reports suggested increases in haptoglobin as well as some other acute-phase proteins in depressed patients (Zorrilla et al. Nevertheless, increases in C-reactive protein have been found in association with depression with elevations in healthy depressed adults (Miller et al. In turn, systemic immune activation is thought to lead to endothelial activation in depression with increases in the expression of soluble intercellular adhesion molecule (Lesperance et al. It is not known what mechanisms might account for the dissociation between inflammation and innate immune measures in depression, although genetic and metabolic variation in the expression of proinflammatory cytokines may play a role.
All three studies concluded that there was no evidence that ``the exposure of volunteers to symptoms uterine prolapse cheap leflunomide american express low doses of nerve agents results in any adverse medical sequelae symptoms viral meningitis effective 10 mg leflunomide. Nor were there any differences on these measures between those exposed to symptoms 8 weeks pregnant buy 20 mg leflunomide mastercard sarin and control groups of volunteers who were not exposed. Likewise, there was no evidence of long-term psychiatric symptoms or in the type of illnesses that the exposed versus control groups experienced. The Presidential Advisory Committee also looked at short- and long-term health effects of selected Gulf War risk factors, for example, chemical=biological weapons, depleted uranium, infectious diseases, anti-biological warfare vaccines, pyridostigmine bromide, and so on. The Presidential Advisory Committee gave specific and serious attention to the question of health effects of low-level exposure to nerve agents. Such an increased level of research has already been initiated and some elements of it are discussed throughout this chapter. Since the end of the first Gulf War there has developed a substantial literature, in the form of review papers, on potential long-term health effects from low-level exposure to nerve chemical warfare agents. These papers have presented slightly different analyses of this issue and, not surprisingly, they have reached slightly different conclusions. However, we do highlight several papers to show the controversies within the field, as well as areas of consensus. Thus, they argued that exposures could be characterized as high, 74 Chemical Warfare Agents: Chemistry, Pharmacology, Toxicology, and Therapeutics intermediate, or low, depending upon factors such as intensity of cholinergic signs. Clearly identified long-term effects have been noted at or above their defined intermediate level exposure. Long-term health effects, according to Brown and Brix (1998), are not reported in individuals experiencing repeated low-level exposure alone. In his brief review of chronic effects of low-level exposure to anti-ChEs, Roy (1998) concluded that ``concerns about major adverse health effects of low-level exposure to anti-ChEs in general seem entirely unwarranted on the basis of currently available literature, but the data are at present insufficient to reflect the possibilities of subtle, agent-specific effects. It is a common practice for toxicologists to differentiate exposure to chemicals based on the dose and the duration of exposure. Four time frames have been used to define duration of exposures: acute, subacute, subchronic, and chronic. When referring to an inhalation exposure, the exposure duration most frequently used is 4 h. These exposures can be by any route; for most chemicals, it is the oral route with the chemical given in the diet (Klaasen and Eaton, 1991). The limited animal studies using nerve agents have usually employed parenteral administration of the agent and virtually all of them involve acute or subacute durations of exposure. These appear to range from any nonlethal exposure through ``subtoxic' (defined by DeMenti [1999] as no clinical signs) to ``subclinical' (defined by DeMenti [ibid. Exposure, then, is any contact with a chemical that may induce a biochemical effect. For the purposes of this review, we will attempt to characterize each paper in terms of presence=absence of either clinical signs or symptoms (in the case of human studies) and level and type of ChE inhibition. With respect to epidemiological research studies, Smith, Gray, and colleagues reported on continuing efforts to assess plausible relationships among potential Gulf War exposures and health effect outcomes. Between 1999 and 2003 there were improvements and refinements of exposure estimates, as well as improvements in regression modeling of hospitalizations. In summary, even after employing refined exposure estimates and up to a greater than 10 year postwar hospitalization window, these authors were unable to conclude that Gulf War veterans are at greater risk of hospitalization due to a specific exposure-related disease. While pertinent, extrapolation from these exposures to predictions of effects from nerve agents may be subject to Health Effects of Low-Level Exposure to Nerve Agents 75 risk. They also noted that the more severely exposed individuals or those with multiple exposures tended to display persistent symptoms that included forgetfulness, irritability, and confused thinking, although the duration of these persistent symptoms was never clearly defined. These effects began coincident with the depression of plasma and red-blood cell ChE activity to approximately 60% and 50% of original activity, respectively, following a single i. Psychological=behavioral effects were typically evident before the occurrence of physical symptoms.
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