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Repeated exposure to certain solvents may the effects of a toxic substance may vary dramati produce immediate effects after each dosing as well cally diabetes diet chart 2mg amaryl mastercard, depending on the stage of maturation of the as delayed adverse effects from long-term exposure animal diabetes medications patient handout discount amaryl online master card. Acute toxic responses result when an animal is Most preliminary assessments are designed to pro subjected to high concentrations of a substance over vide information on the population with the greatest a short period of time diabetic diet understanding order amaryl visa. However diabetes test in toddlers generic amaryl 1mg line, sudden and severe diabetes prevention program knowler effective amaryl 4mg, and usually lasts for a brief aged populations or those undergoing rapid matura period of time; in some cases diabetes urine test order amaryl 4 mg overnight delivery, however, it is tion are often especially vulnerable to environmental permanent. If the dose is sufficiently high, death may exposures; thus, tests to assess the neurobehavioral result. Lower doses (lower concentrations over functioning of these populations are necessary for a longer periods of time) may not immediately cause complete evaluation. As the dose decreases, the response is generally less severe and may take longer to the ideal tests are those that permit longitudinal develop. In chronic exposures, clinically adverse assessment of animals of both sexes at any stage of effects may take years to develop (47). Although substances generally produce the greatest effect and Dosing Regimen most rapid response when given intravenously, this Some compounds produce one kind of toxic effect is an unlikely route of entry except in the case of following a single exposure and other effects follow drug therapies or drug abuse. In environmental a potentially toxic agent enters the body can toxicology, a major objective is the detection of influence the time of onset, intensity, and duration of cumulative toxicity following continued (or inter the toxic effects. Thus, a multiple-dosing regimen influence the degree of toxicity and the organs most is most commonly used. Re contaminants from the air before they enter the peated exposures are divided into subacute, sub respiratory tract. Subacute exposure reach the alveoli of the lungs (where gas exchange refers to repeated exposure to a chemical for 1 takes place), it must be either a gas or of a certain month or less, subchronic exposure occurs typi particulate size (less than 10 microns in diameter) so cally from 1 to 3 months, and chronic exposures that it is not removed in the airway to the lungs. This may occur because of compensatory changes Most episodes of acute toxicity result from elicited by repeated administration or because of intentional or accidental ingestion of a chemical. For cumulative effects of mechanisms different from instance, a person may deliberately take an overdose those causing acute toxicity. Poisonous mushrooms may primary acute toxic effect of carbon disulfide is be accidentally ingested. Sufficiently large particles depression of central nervous system activity; how of inhaled toxic matter may collect in the throat and ever, repeated exposures can result in peripheral be swallowed. Acute exposure to rapidly absorbed substances is likely to produce the simplest route of exposure for humans and immediate toxic effects, but acute exposure can also animals is accidental or intentional contact of the produce prolonged toxicity that may or may not be chemical with the skin. A single dose of a compound that enced by the type of compound(s) involved and the produces an immediate, severe effect might produce condition of the skin. For example, cuts or abrasions less than half the effect when given in two equal on the skins surface will allow the agent to bypass doses and no effect when given in 10 doses over a the epidermis, the outer, protective layer of the skin. Chronic toxic effects Once through the epidermis, the substance can easily occur if the compound accumulates in the organ pass into the circulatory system. Depending on the isms system, if it produces irreversible toxic effects, concentration and duration of the exposure, some or if there is insufficient time for the system to substances, solvents, for example, can easily pass recover from the toxic damage (47). Other Considerations Extent and Duration of Exposure Several additional factors are considered in de the exposure of animals to chemicals is often signing neurotoxicological tests. One condition that divided into four categories: acute, subacute, sub may affect toxicity is the nutritional state of the chronic, and chronic. The purpose might be due to relatively nonspecific effects related of an acute test is to observe the evidence of toxicity to inhibition of growth or decreases in food or water after administration of the compound and the degree consumption. While acute exposure usually refers to a single administration, repeated or continuous Another factor is the housing conditions of the doses may be given within a 24-hour period for some experimental animals. An example housed individually in cages during toxicological Chapter S-Testing and Monitoring q 109 studies, an arrangement that may alter their respon siveness to the test compounds. For example, a chemical that causes depletion of the neurotransmit ters norepinephrine and dopamine produces less depression of motor activity in isolated rats than in grouped rats (125). Normally, the response of an animal to a toxic compound decreases as the environmental temperature is lowered, but the dura tion of the overall response may be delayed. Also, some drugs are more toxic in certain environmental temperatures than in others. For example, com pounds affecting the neurotransmitter acetylcholine may produce significantly greater toxicity in a warm environment than in a colder one. Eventually, the body temperature becomes elevated because the absence of perspira tion prevents cooling (38). In such a case, toxic effects may result from hyperthermia, not directly from the effect of the substance on the nervous system. Environmental Protection Agency Validation However, it may be possible through a well developed screening program to flag the substances Validation is a critical component of the test either currently in use or recently introduced that development process because it ensures that data have neurotoxic potential. Screening is conducted to generated as a result of testing will be useful in provide an initial evaluation of the effects of various evaluating the health risk posed by a particular substances on the nervous system. The value of any toxicity test lies in its screening may be used to reduce the number or ability to measure the endpoint it is designed to quantity of hazardous substances in commerce or to detect. For neurotoxicity, the endpoints are adverse aid in determining which additional studies should changes in the structure or function of the nervous be undertaken to further characterize their toxicolog system. An efficient screen should usually requires demonstration that the test is reliable, sensitive, and specific. For validation stud evaluate a variety of neurological effects rather than ies, chemicals with known neurotoxic potential and just one. Screens should also be sensitive, reproduc those known not to be neurotoxic are studied to ible, and capable of being administered rapidly determine the ability of the test to distinguish (32,33), between them. Because toxic substances can have many different effects on the nervous system, known Testing strategies often involve a tiered approach. In the initial screen of the tiered testing clude a multilaboratory phase to test the reproduci approach, the outcomes of acute studies are inter bility of the testing paradigm in different laborato preted. The third tier is composed of Evaluating Chemicals for Neurotoxicity detailed studies of subtle effects or mechanisms of It is impossible to thoroughly examine the neuro toxicity. At each stage the examiner builds on the toxicity of each of the chemicals in commerce. Neurotoxicity: Identifying and Controlling Poisons of the Nervous System Typically, 5 to 10 animals of the same species and dermal, inhalation, and oral exposure); subpart C strain are used in the tests. It is important to select the includes testing procedures for subchronic dermal, proper animal model initially because it is desirable inhalation, and oral exposure; and subpart D de to use the same model in subsequent tiers. Some toxicity tests only General toxicological tests evaluate a broad require the acute dosing regimen, and it is not spectrum of potential toxicological effects, includ necessary to conduct repeated dosages. Box 5-A ing some effects on the nervous system; however, illustrates one example of a tiered testing approach. In vitro tests will be described later in this thology, and the effects of organophosphorous chapter. At the present time, these three tests are icity tests for use in regulatory programs. The guidelines are use the core tests routinely in evaluating new and old categorized into three subparts: subpart B describes chemicals and pesticide products. Box 5-ATiered Animal Testing To Identify Adverse Neurobehavioral Effects of Substances Tiered testing is an efficient and cost-effective approach to evaluate the toxicity of chemicals. In the first tier of an experiment, the recommended strategy is to identify acute hazards of substances. The second tier is designed to characterize the toxicity in repeated exposure, and the third is used to undertake detailed studies of special impairments or of mechanisms of chemical injury. The investigator seeks to identify any evidence of mortality, morbidity, or morphological changes. The first tier helps establish the parameters of exposure that are appropriate for the second tier. It may also suggest mechanisms by which the effect is produced, which may assist in the design of more sensitive experiments in the third tier. Second tierAnimals are repeatedly or continuously exposed to substances being evaluated. This tier provides an opportunity to characterize delayed toxicity, to observe the development of tolerance, and to characterize the reversibility of adverse effects. Third tierAt this stage, highly focused studies are performed to fully characterize toxicity, using methods dictated by the nature of the system. This tier can identify subtle sensory or perceptual impairments, affective disorders, or cognitive and intellectual dysfunction. A detailed hazard characterization not only can facilitate the identification of the most sensitive situation, but also may clarify the mechanism of action of the substance. The above schemes may be modified in the future as in vitro tests become available. Frazier, Alternatives to Animals in Toxicity Testing, Scientific American 1989; Wood, American Psychological Association, testimony before the of the Science Advisory Panel, U. It serves as a screening tool (thus, it is identifying hazardous chemicals and are not specifi considered a first tier test), indicating which sub cally designed to develop the data necessary for stances should be further characterized using second full-scale risk assessments (101). Some neurotoxicologists have challenged the Three doses of the test substances are used, with usefulness of the core battery, saying that it does not doses chosen so that the highest dose produces go far enough. The doses are selected on just the core battery, with the option of using more the basis of values from previous literature and comprehensive tests for selected compounds. The observer developmental neurotoxicity, and neurotoxic est records each response subjectively, using estab erase assay (101). After all data are collected, they are entered into a computer, summarized, and Which tests are most appropriate for routine use analyzed using statistical methods (17,68-70). Box in screening for neurotoxicity is the subject of 5-B summarizes the procedures for conducting the disagreement in the scientific community. Potential problems include difficulty in enable investigators to judge whether or not addi defining certain measures, a tendency toward sub tional (second tier) testing is necessary. Descriptions jective biases in assessing behavior (123), and the of various neurotoxicity tests follow. Next, the animal is picked up and rated for ease of handling and removal from the cage. The rat is observed and rated for signs, such as lacrimation and salivation, that the autonomic nervous system has been adversely affected. The rat is then placed on a cart top for 3 minutes, during which time the number of rears are counted and the gait, mobility, and level of arousal are rated. Next, the technician rates the rats responses to several stimuli, such as the approach of a pencil, snap of a metal clicker, touch of the pencil on the rats rump, and pinch of the tail with forceps. Using a pen flashlight, the observer tests the rat for pupil constriction in response to light. The righting reflex is then measured by the ability of the rat to flip over in midair and land on its feet. The rats hind feet are painted, and the technician then holds the rat a few inches above the cart top and drops it in order to measure landing foot splay. There is disagreement as to whether motor activity is a primary indicator of neurotoxic ity. For example, the primary action of a toxicant may be at some site other than the nervous system; the changes in motor activity maybe secondary, that is, a result of the primary effect. The quantitative approach measures the frequency, duration, and sequencing of various Motor Activity motor components of behavior. The qualitative approach is used to gather data on the presence or Motor activity is generally defined as any move absence of certain components of activity (90). The the use of observational methods to detect subtle acute motor activity test is used to examine changes changes in behavior has limitations. Many man in animal movement following the administration of hours are required to obtain and evaluate the data. The subchronic motor activity test is used observer interaction is an important consideration. Chapter 5Testing and Monitoring q 113 For example, the presence of the observer may Figure 5-lThe Effects of Toxic Substances modify the animals behavior (90). In most cases, videotaping has 400 minimized the problem of subject-observer interac tion and has provided a permanent record of 300 280 behavior which can be used for standardizing observations. The computer techniques have allevi 235 ated the problems of subjectivity (subject-observer 200 interaction and subjective bias) and laborious data collection procedures (90). Triad ures of motor activity in which beams of light traverse a cage and collide with photoreceptors. The number Hyperactivity, of beam interruptions is counted and recorded by a 330, 1989; and Potential of Pesticides: Age-related Effects of computer for a l-hour time period (60,68). Environmental Pro figure-8 maze is only one of a variety of chambers tection Agency report, Health Effects Research Laboratory, 1985. For example, another device commonly employed for assessing motor activity is the Motron Electronic Mobility to determine how motor activity changes with level Meter, which differs from the figure-8 maze because of exposure (59). Automated motor activity meas vices involve a vertical or horizontal displacement ures may be used to generate dose-response data. This is typically done by placing rats in a plexiglass Some of the mechanical devices used include box, Two video cameras monitor the animals stabilimeters and running wheels. Stabilimeters behavior, and the video signals are transferred to record the movement of the animal when it causes computers in order to identify common patterns in the chamber floor to be displaced from its resting movement and behavioral classification of the data position. To generate the data illustrated in ning wheels have been used in behavioral toxicology figure 5-1, motor activity was measured for 1 hour for over three-quarters of a century to study the in a group of rats in a figure-8 maze after administra effects of food deprivation, water deprivation, es tion of a toxic substance or placebo (P). The numbers trus, lesions of the central nervous system, and represent motor activity units for the entire hour. Neurotoxicity: Identifying and Controlling Poisons of the Nervous System There are many advantages of motor activity tests. These include the availability of automated test equipment, ease of testing, and objectivity of data (60). Additional factors include obtaining reproduci ble data that are sensitive to the effects of acute exposure to various toxic substances.

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It is important to note that the committee was not tasked with assessing the benefts (effectiveness) of vaccines or any policy issues related to vaccination diabetes mellitus oms buy generic amaryl pills. Chapters 411 present the evidence reviewed by the committee for each of the eight vaccines covered and the conclusions it reaches diabetes prevention articles buy amaryl 4 mg with visa. Chapter 12 presents causality assessments for adverse events that can occur with any injected vaccine regardless of the vaccine antigen and components control diabetes food amaryl 2 mg low price. Annual summary of vital statistics: Trends in the health of Americans during the 20th century diabetes type 1 unplanned pregnancy buy amaryl 2 mg with amex. Adverse effects of pertussis and rubella vaccines: A report of the committee to review the adverse consequences of pertussis and rubella vaccines diabetes test your knowledge purchase 1 mg amaryl. Immunization safety review: Thimerosal-containing vaccines and neuro developmental disorders diabetes prevalence discount 4mg amaryl amex. Immunization safety review: Hepatitis B vaccine and demyelinating neurological disorders. Charge to the Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality Copyright National Academy of Sciences. The categories used previously were considered appropriate and the benefts of consistency were deemed compelling enough to extend the categories to this report. Two streams of evidence from the peer-reviewed literature support the committees causality conclusions: (1) epidemiologic evidence derived from studies of populations (most often based on observational designs but ran domized trials when available), and (2) clinical and biological (mechanistic) evidence derived primarily from studies in animals and individual humans or small groups. Some studies provide evidence relevant to both epidemio logic and mechanistic questions. Drawing from both lines of evidence to support causal inference is well established in the literature. The frst wave of searches included the earliest date of the database to the date of the frst search. Follow-up searches were conducted in August 2010 and late December 2010 to ensure that articles published after the initial search were not missed. On occasion, specialized searches were conducted to supplement the general searches. Also, review of the reference list of an article sometimes revealed studies not captured by the general search. Titles and abstracts, where available, were reviewed to screen out articles that did not address one of the potential vaccine adverse events to be reviewed or that were not primary research articles. The committee restricted its review to those vaccines used in the United States, even if the study was conducted outside of the United States, with a few exceptions that will be discussed in the vaccine-specifc chapters that follow. Articles written in languages other than English were translated using Google Translate or a professional translation service. The committee did not include in its reviews data presented only in abstract form or in oth erwise unpublished formats, with one exception described in Chapter 9, Human Papillomavirus Vaccine. Decisions from the Vaccine Injury Compensation Program were not reviewed, because they are not published in the peer-reviewed medical literature. Adverse Effects of Vaccines: Evidence and Causality 41 Copyright National Academy of Sciences. Section I contained those articles on which the committee focused its initial review. The frst assessment applies to the weight of evidence from the epide miologic literature; the second applies to the weight of evidence from the biological and clinical (mechanistic) literature. In assessing the weights of evidence, each individual article (or fndings within an article if more than one outcome or vaccine was studied) was evaluated for its strengths and weaknesses. The committee then synthesized the body of evidence of each type (epidemiologic or mechanistic) and assigned a weight of evidence for each. These weights of evidence are meant to summarize the assessment of the quality and quantity of evidence. The committee then reviewed the two weight-of-evidence assessments in order to make a conclusion about the causal relationship. The committees approach to each of these three assessments will be discussed in the following sections. Epidemiologic Evidence Experimental studies (trials) are generally considered more rigorous than observational studies; controlled studies are generally considered more rigorous than uncontrolled studies. A brief description of major study designs and methodological considerations can be found in Appendix A. Surveillance studies were reviewed, but the absence of a control group lim ited their contribution to the weight of epidemiologic evidence; studies that included individual case descriptions were reviewed for their contribution to the evaluation of mechanistic evidence (discussed in subsequent sections). Small clinical studies that were not controlled for vaccine administration were generally reviewed for contributions to the mechanistic weight of evidence. Studies that were deemed to be very seriously fawed did not contribute to the weight of evidence; they are identifed in the text for completeness but are not discussed in depth. It is important to note that a specifc study could be well designed and well conducted but also have very serious limitations for the purposes of this committees analysis. A specifc study could have fewer limitations for some vaccines or some outcomes than for others. Small clinical studies can be well conducted but the number of subjects may be too small to detect most adverse events. Although most effcacy studies include a safety com ponent, the results are often nonspecifc (e. Studies in which no cases of a specifc adverse event were identifed are uninformative for this review, because if the vaccinated cohort does not include enough cases to approximate background rates, the study is under powered to inform an assessment. The upper limit of the 95% confdence interval will always overlap with the background rate unless the vaccine is protective. Some might use that information as means to approximate an upper limit on risk, but the committee did not see that as its charge (see Chapter 13). Studies such as these were considered to have very serious limitations for the purpose of the committees assessment. The committee was rigorous in assessing the strengths and weaknesses of each epidemiologic study. For many of the conditions and adverse events considered by the committee, the expected incidence and prevalence rates in the general unvaccinated population as well as in unvaccinated but po tentially susceptible subgroups may be very low. Although randomized clinical trials aiming to study vaccine effcacy may provide the most valid, controlled circumstances in which to also study vaccine safety, such trials inevitably enroll too few study par Copyright National Academy of Sciences. Some studies, as will be documented in chapters that follow, reviewed are likely the most meth odologically sound that can be done given the nature of the exposure and the outcomes, even if the studies have some residual limitation due to the challenges that often attend such research. The reader will see in the sum mary paragraphs for the epidemiologic studies and, in some circumstances, the causality conclusion the committees interpretation of the evidence more fully than can be captured with the formal and consistent wording of the conclusions used in this report. Evaluation of the Body of Studies the committee reviewed methodological approaches of other system atic review efforts, but it was unable to identify one approach that incor porated all of the committees needs and could be adopted for immediate use. Cochrane reviews, for example, focus on randomized controlled trials, which is an uncommon design in vaccine safety studies. Other efforts focused on evidence for or against a clinical practice or intervention (Guyatt et al. Consequently, the committee adopted key components of these other approaches to develop a summary classifcation scheme that incorporates both the quality and quantity of the individual studies and the consistency of the group of studies in terms of direction of effect. A key concept to these classifcations is confdence, which refers to the confdence the committee has that the true effect lies close to that of the estimate of the average overall effect for the body of evidence. Validity refers to the absence of confounding, selection bias and information or measurement bias. The wider the 95% confdence inter vals, the less statistical power to detect a difference as signifcant. The four weight-of-evidence assessments for the epidemiologic litera ture are as follows: High: Two or more studies with negligible methodological limita tions that are consistent in terms of the direction of the effect and taken together provide high confdence. These are to indicate increased risk of the adverse event, decreased risk of the adverse event, or no change (null) in the risk of the adverse event. The committee does not consider a single studyregardless of how well it is designed, the size of the estimated effect, or the narrowness of the confdence intervalsuffcient to merit a weight of high or, in the absence of strong or intermediate mechanistic evidence, suffcient to sup port a causality conclusion other than inadequate to accept or reject a causal relationship. However, the Agency for Healthcare Research and Quality advises the Evidence-based Practice Centers that it has funded to produce evidence reports on important issues in health care to view an evidence base of a single study with caution (Owens et al. It does so due to the inabil ity to judge consistency of results, an important contributor to a strength of evidence, because one cannot be certain that a single trial, no matter how large or well designed, presents the defnitive picture of any particular clinical beneft or harm for a given treatment (Owens et al. However, the committee is not recommending policy, rather evaluating the evidence using a transparent and justifable framework. Mechanistic Evidence the committee assessed the mechanisms of vaccine adverse events by identifying and evaluating clinical and biological evidence. First, the com mittee looked for evidence in the peer-reviewed literature that a vaccine was or may be a cause of an adverse event in one or more persons (from case reports or clinical studies) in a reasonable time period after the vaccination. Then the committee looked for other information from the clinical and biological (human, animal, or in vitro studies) literature that would provide evidence of a pathophysiological process or mechanism that is reasonably likely to cause the adverse event or to occur in response to specifc im munization. Chapter 3 contains a discussion of the major mechanisms the Copyright National Academy of Sciences. The committee identifed many case reports in the literature describ ing adverse events following vaccination. For the purposes of this report, case report refers to a description of an individual patient; one publication could describe multiple case reports. The cases considered by the commit tee in weighing evidence of mechanisms were not derived from the large epidemiology studies considered above; there was no double counting. At a minimum, for a case to factor into the weight-of-evidence assessment, it had to include specifc mention of the vaccine administered, evidence of clinician-diagnosed health outcome,3 and a specifed and reasonable time interval. As discussed in the next section, however, these three criteria were only necessary but not suffcient to affect the weight of mechanistic evidence. After identifying cases with the three basic elements, the committee looked for evidence in the case descriptions and in other clinical or biological litera ture of a possible operative mechanism(s) that would support a judgment that the vaccination was related to the adverse event. See Chapter 3 for a description of possible mechanisms identifed by the committee. Rechallenge cases, in which an adverse event occurred after more than one administration of a particular vaccine in the same individual, could infuence the weight of evidence. Each rechallenge, however, must meet the same attributes of reasonable latency, documentation of vaccination receipt, and clinician diagnosis of the health outcome. It is possible that one or more of the challenges in an individual case patient reporting is related to a coincidental exposure; thus, the committee looked for other information, as described below, that would support a role for the vaccine in each challenge. The value for the committee of rechallenge cases is much greater for monophasic conditions (events that typically happen only once, 3On occasion, the case report author describes clinical test results or observations but does not proffer a diagnosis. In these cases, the committee assigned the case report to the health outcome it felt appropriate. Some authors of older case reports use a diagnosis appropriate for the time, but by todays understanding of clinical disease and pathophysiology, the committee offers a different diagnosis and the case report is described within that committee-directed assessment. For example, most adverse reactions from live virus vaccines would not be expected to occur within hours of vaccination; rather, time must elapse for viral replication. Another factor that affected the weight of evidence was information in the clinical workup that eliminated well-accepted alternative explanations for the condition, thus increasing the possibility that the vaccine could be associated with the adverse event. Another particularly strong piece of evidence in the case description that affected the weight of evidence is isolation of vaccine strain virus from the patient. Evidence from animal studies is also informative if the model of the disease is well established as applicable to humans or if the basic immunol ogy of the vaccine reaction is well understood. In vitro studies can also be informative, but such data must be eyed with skepticism regarding their relationship to the human experience. Specifc examples of relevant clinical or biological information are discussed in Chapter 3 generally and in the vaccine-specifc Chapters 4 through 11. The committee also searched for other appropriate frameworks for evaluating biological evidence as support for causation analyses. Each category includes consideration of the clinical information from case reports and consideration of clinical and experimental evidence from other sources. Evidence consisting only of parallels with the natural infections is never suffcient to merit a conclusion other than the evidence is inadequate to accept or reject a causal relationship. On occasion, the committee determined that at least two cases, taken together, while suggestive, are nonetheless insuffcient for the com mittee to conclude the vaccine may be a contributing cause of the adverse event, based on an overall assessment of attribution in the available cases and clinical, diagnostic, or experimental evidence consistent with relevant biological response to vaccine. Implicit in these categories is that the absence of evidence is not evidence of absence. The committee then 6The committee considered the clinical manifestations of the natural infection against which the vaccine is directed to be suffcient for a weight of evidence of weak, rather than lacking. As will be discussed in a subsequent section, a mechanism weight of evidence of weak alone is never suffcient to support a causality conclusion other than the evidence is inadequate to accept or reject a causal relationship. The following are the categories of causation used by the committee: Evidence convincingly supports7 a causal relationshipThis ap plies to relationships in which the causal link is convincing, as with the oral polio vaccine and vaccine-associated paralytic polio. The category of establishes or convincingly supports no causal rela tionship is not used because it is virtually impossible to prove the absence of a relationship with the same certainty that is possible in establishing the presence of one. Even in the presence of a convincing protective effect of vaccine in epidemiology, studies may not rule out the possibility that the re action is caused by vaccine in a subset of individuals. The committee began not by assuming the causal relationship does not exist, but by requiring evidence to shift away from the neutral position that the evidence is inadequate to accept or reject a causal relationship. The committee then established a general framework by which the two streams of evidence (epidemiologic and mechanistic) infuence the fnal causality conclusion. This framework needed to ac commodate the reality that for any given causality conclusion one or both of the types of evidence could be lacking, the two types of evidence could confict, or neither type of evidence might defnitively infuence the causal ity conclusion. The framework also had to accommodate known limitations of both types of evidence. Epidemiologic analyses are usually unable to detect an increased or decreased risk that is small, unless the study population is very large or the difference between the groups (e. Epidemiologic analyses also cannot identify with cer tainty which individual in a population at risk will develop a given condi tion. These studies also can fail to detect risks that affect a small subset of the population. Mechanistic evidence, particularly that emerging from case reports, occasionally can provide compelling evidence of an association between exposure to a vaccine and an adverse reaction in the individual being studied, but it provides no meaningful information about the degree of risk to the population or even to other individuals who have the same predisposing characteristics.

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Age and risk factors for colon cancer (United States and Australia): Are there implications for understanding dif ferences in case-control and cohort studies Could dietary fat intake be an important determinant of seasonal weight changes in a rural subsistence farming community in the Gambia Macronutrients and plasma triglycerides diabetes mellitus definition emedicine 1mg amaryl, high-density lipoprotein diabetes type 1 and 2 yahoo generic amaryl 2 mg with visa, and the ratio of total to high-density lipoprotein cholesterol in women: the Framingham Nutrition Studies blood glucose sliding scale order amaryl 4 mg without prescription. Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults diabetes mellitus type 2 insulin dependent purchase generic amaryl pills. Influence of dietary fat composition on development of insulin resistance in rats diabetes mellitus blood test amaryl 1mg with visa. Dietary Reference Intakes: the Essential Guide to Nutrient Requirements blood glucose units of measurement order amaryl 2 mg online. Hypotensive effect of low-fat, high-carbohydrate diet can be independent of changes in plasma insulin concentrations. Early lesions of athero sclerosis in childhood and youth: Natural history and risk factors. Covert manipulation of dietary fat and energy density: Effect on substrate flux and food intake in men eating ad libitum. Covert manipulation of the ratio of dietary fat to carbohydrate and energy density: Effect on food intake and energy balance in free-living men eating ad libitum. Covert manipulation of the dietary fat to carbohydrate ratio of isoenergetically dense diets: Effect on food intake in feeding men ad libitum. Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats. Deteriora tion in carbohydrate metabolism and lipoprotein changes induced by modern, high fat diet in Pima Indians and Caucasians. Long-term (5-year) effects of a reduced-fat diet intervention in individuals with glucose intolerance. Effect of omega 3 and omega 6 fatty acids on transformation of cultured cells by irra diation and transfection. Effects of feeding 4 levels of soy protein for 3 and 6 wk on blood lipids and apolipoproteins in moderately hypercholesterolemic men. Nutrient balance and energy expenditure during ad libitum feeding of high-fat and high-carbohydrate diets in humans. Thomsen C, Rasmussen O, Christiansen C, Pedersen E, Vesterlund M, Storm H, Ingerslev J, Hermansen K. Comparison of the effects of a monounsaturated fat diet and a high carbohydrate diet on cardiovascular risk factors in first degree relatives to type-2 diabetic subjects. Dietary Reference Intakes: the Essential Guide to Nutrient Requirements. Relation of dietary carbo hydrates to blood lipids in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. Consumption of meat, animal products, protein, and fat and risk of breast cancer: A prospective cohort study in New York. Nutritional determinants of the increase in energy intake associated with a high-fat diet. Prolonged inhibition of platelet aggregation after n-3 fatty acid ethyl ester ingestion by healthy volunteers. Trevisan M, Krogh V, Freudenheim J, Blake A, Muti P, Panico S, Farinaro E, Mancini M, Menotti A, Ricci G. Consumption of olive oil, butter, and vegetable oils and coronary heart disease risk factors. Trichopoulou A, Katsouyanni K, Stuver S, Tzala L, Gnardellis C, Rimm E, Trichopoulos D. Consumption of olive oil and specific food groups in relation to breast cancer risk in Greece. Effect of acetate and propionate on calcium absorption from the rectum and distal colon of humans. Over weight prevalence and trend for children and adolescents: the National Health and Nutrition Examination Surveys, 1963 to 1991. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim H-J, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Dietary Reference Intakes: the Essential Guide to Nutrient Requirements. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. Effects of a fish-oil and vegetable oil formula on aggregation and ethanolamine-containing lysophospholipid generation in activated human platelets and on leukotriene production in stimulated neutrophils. Insulin resistance, impaired glucose tolerance and non-insulin-dependent diabetes, pathologic mechanisms and treatment: Current status and therapeutic possibilities. Uematsu T, Nagashima S, Niwa M, Kohno K, Sassa T, Ishii M, Tomono Y, Yamato C, Kanamaru M. Uusitupa M, Schwab U, Makimattila S, Karhapaa P, Sarkkinen E, Maliranta H, Agren J, Penttila I. Effects of two high-fat diets with different fatty acid compositions on glucose and lipid metabolism in healthy young women. Effects of varying the carbohydrate:fat ratio in a hot lunch on post prandial variables in male volunteers. A prospective cohort study on dietary fat and the risk of postmenopausal breast cancer. Effects of dietary fat modifications on serum lipids and blood pressure in children. Dietary fat intake and risk of lung cancer: A prospective study of 51,452 Norwegian men and women. Dietary fat intake and risk of prostate cancer: A prospective study of 25,708 Norwegian men. Dietary Reference Intakes: the Essential Guide to Nutrient Requirements. Dietary fat, fat subtypes, and breast cancer in postmenopausal women: A prospective cohort study. High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart disease. Comparison of nutrition as customary in the Western World, the Orient, and northern populations (Eskimos) in relation to specific disease risk. Boys from populations with high-carbohydrate intake have higher fasting triglyceride levels than boys from populations with high-fat intake. Calciuric effects of protein and potassium bicarbonate but not of sodium chloride or phosphate can be detected acutely in adult women and men. Dietary Reference Intakes: the Essential Guide to Nutrient Requirements. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. Meal energy density as a determinant of postprandial gastrointestinal adaptation in man. Metabolizable energy of diets low or high in dietary fiber from cereals when eaten by humans. Replacement of carbohydrate by protein in a conventional-fat diet reduced cholesterol and triglyceride concentrations in healthy normolipidemic subjects. Wolk A, Bergstrom R, Hunter D, Willett W, Ljung H, Holmberg L, Bergkvist L, Bruce A, Adami H-O. A prospective study of association of mono unsaturated fat and other types of fat with risk of breast cancer. Physiologic versus cognitive factors in short term food regulation in the obese and nonobese. Dietary choles terol, fat, and lung cancer incidence among older women: the Iowa Womens Health Study (United States). Independent effects of palatability and within-meal pauses on intake and appetite ratings in human volunteers. Effect of dietary macronutrient composition on tissue-specific lipoprotein lipase activity and insulin action in normal-weight subjects. Conjugated linoleic acid supplementation in humans: Effects of body composition and energy expenditure. Dietary Reference Intakes: the Essential Guide to Nutrient Requirements. Fish consumption and mortality from all causes, ischemic heart disease, and stroke: An ecological study. Dose-response effects of dietary a-linolenic acid enriched oils on human polymorphonuclear-neutrophil biosynthesis of leukotriene B4. Hydrogenation alternatives: Effects of trans fatty acids and stearic acid versus linoleic acid on serum lipids and lipoproteins in humans. Dietary Reference Intakes: the Essential Guide to Nutrient Requirements. Short-term energy balance: Relationship with protein, carbohydrate, and fat balances. Studies in human lactation: Milk composition and daily secretion rates of macronutrients in the first year of lactation. The safety and efficacy of a controlled low-energy (very-low-calorie) diet in the treatment of non-insulin-dependent diabetes and obesity. Energy and macronutrient content of human milk during early lactation from mothers giving birth prematurely and at term. Metabolic and endocrine responses to cold air in women differing in aerobic capacity. Metabolic rates during recovery from proteincalorie malnutrition: the need for a new concept of specific dynamic action. Glucose metabolism during fasting through human pregnancy: Comparison of tracer method with respiratory calorimetry. Obesity as an adaptation to a high-fat diet: Evidence from a cross-sectional study. Impact of the v/v 55 polymorphism of the uncoupling protein 2 gene on 24-h energy expenditure and substrate oxidation. Interrelation of age, obesity, cigarette smoking, and blood pressure in hypertensive patients. Dietary Reference Intakes: the Essential Guide to Nutrient Requirements. A meta-analysis of the factors affecting exercise induced changes in body mass, fat mass and fat-free mass in males and females. Psychological measures of eating behavior and the accuracy of 3 common dietary assessment methods in healthy postmenopausal women. A Metabolic Study with Special Refer ence to the Efficiency of the Human Body as a Machine. The Gaseous Metabolism of Infants, with Special Reference to its Relation of Pulse-Rate and Muscular Activity. Using biochemical markers to assess the validity of prospective dietary assessment methods and the effect of energy adjustment. Comparison of dietary assessment methods in nutritional epi demiology: Weighed records v. Variations and deter minants of energy expenditure as measured by whole-body indirect calorimetry during puberty and adolescence. Total energy expenditure and spontaneous activity in relation to training in obese boys. Measurements of total energy expenditure provide insights into the validity of dietary measurements of energy intake. Dietary Reference Intakes: the Essential Guide to Nutrient Requirements. Human energy expenditure in affluent societies: An analysis of 574 doubly-labelled water measurements. Thermogenic response to temperature, exercise and food stimuli in lean and obese women, studied by 24 h direct calorimetry. Thermogenic response to an oral glucose load in man: Comparison between young and elderly subjects. Daily energy expendi ture and physical activity assessed by an activity diary in 374 randomly selected 15-year-old adolescents. The effects of body weight on serum cholesterol, serum triglycerides, serum urate and systolic blood pressure. Dietary methods research in the Third National Health and Nutrition Examination Survey: Underreporting of energy intake. Muscle accounts for glucose disposal but not lactate appearance during exercise after acclimatization to 4,300 m. Effect of moderate cold exposure on 24-h energy expenditure: Similar response in postobese and nonobese women. Dietary Reference Intakes: the Essential Guide to Nutrient Requirements. Energy expenditure variations in soldiers performing military activities under cold and hot climate conditions. Energy expen diture and deposition of breast-fed and formula-fed infants during early in fancy. Adjustments in energy expenditure and substrate utilization during late pregnancy and lacta tion. Energy requirements derived from total energy expenditure and energy depo sition during the first 2 y of life.

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As a result diabetes mellitus x insipidus discount amaryl online american express, culture and religion med them that a note taker would record their res play important role in their perception diabetes symptoms and types amaryl 2mg lowest price, attitude and practice of procreation diabetes symptoms gas generic amaryl 2 mg mastercard. This diabetes type 1 zwangerschap purchase amaryl 2mg overnight delivery, however diabetes diet help purchase cheap amaryl, they exhibit in their day-to-day interpersonal interactions diabetes mellitus y complicaciones generic 2mg amaryl overnight delivery, within and outside the Participants for the case study were identified during the in-depth interviews and the couples were con church and mosques. Five visits were made to their because of its status as the colonial headquarters of the Yoruba nation. As a result, it attracts Yoruba im homes at agreed hours of the day, mostly after work ing hours. In-depth interviews and non-participant migrants from the other Yoruba towns and villages. Fieldwork Research Participants the fieldwork was conducted by the researcher who In-depth interviews were conducted with 5 couples is a trained and experienced ethnographer. He was who have never conceived or bring pregnancy to assisted by one research Assistant who recorded term after one year of unprotected intercourse, 4 responses. Both the researcher and the note taker adult males, 4 adult females, a geneacologist, a are Yorubas and residents of the study area. The nurse, a herbalist and 2 religious leaders in Ibadan, interviews were conducted in Yoruba Language spo Nigeria making a total of 25 informants. Data collection lasted one range of the couples who participated in the study month. Two of the couples (wives Data Management and husbands) have less than secondary education. Another two had secondary education and one had In order to ensure proper handling of data received, tertiary education. Two couples (wives and hus all tapes were reviewed at the end of each session to bands) were Christians, while three were Muslims. Notes taken Also, two couples (wives and husbands) had married were also reviewed after every interview to be sure for two years while two other couples (wives and that correct responses were recorded by going thro husbands) had married for five years and one for ugh some of the questions randomly with the respon more than five years. This exercise lasted for about 5 munity respondents was between 25 and 70 males minutes. African Journal of Reproductive Health Jun 2010; 14(2): 120 Yoruba Culture and Acceptance of Assisted Reproductive Technologies Method of Data Analysis living. It is believed that a child born out of wedlock may not have similar behaviour pat Data collected were transcribed from tapes and en tern like other members of the lineage. After coding, data were ording to the respondents, sometimes these analyzed using the Atlas ti software. Those who col type of children may bring lineage to disre lected the data from the field and other members of pute. According to a male respondent if a the research group participated in the discussion of child is not directly conceived through the the data before the analysis and report writing. To normal process such a child will not resem achieve the objective of the study research partici ble other members of the family. On the ethical through mechanical process and it has impli dimension, the following issues were discussed cation for the future of such a child. Quoting a verse from the Data reveal that ethical and cultural issues Bible, he said, children are the heritage of are pertinent to the discussion of the use of God and the fruit of the womb is the gain. As a result, the cultural issues confron this was corroborated by the Islamic leader ting the use of the technologies is first pre who said it is a sin for man to compete with sented. Similarly, a Christian male Legitimacy of a child is paramount to mar respondent indicated that one must have riage stability in Yoruba culture. Faith is needed in such a cir nable for a family to go out of wedlock to cumstance not what man can do. It was argued that this can tian wife corroborated the view saying God lead to the problem of identity in the lineage. I dont want to limit His power in linage because of the communal pattern of my life. I have faith that He will do it one African Journal of Reproductive Health Jun 2010; 14(2): 121 Yoruba Culture and Acceptance of Assisted Reproductive Technologies day. A husband was of the opinion that only what to do in case of infertility because wo things that comes from God can last. When men are always blamed for this condition and one bye passes God it can lead to disaster. This view was also shared by a On the other hand, a few respondents were couple who indicated that it should be a joint of the opinion that nothing is wrong with the decision between husband and wife. According to them, God gives ing to the husband I and my wife have been man the knowledge to alleviate his problem. First, it is believed that A female Christian respondent corroborated she may be suffering from the spiritual attack this view saying God says that we shall of the enemy. This view was popular the knowledge is from God to give answer to especially among the herbalist, religious lea human suffering. According to the herbalist, patriarchy is a major cultural factor when ma enemies can cause a woman to be unable king decision about whether or not to use to bear children if they want to punish her. According to a majority of them (80%), this is why a woman must undergo some men dominate decision making about repro ritual for cleansing (Iwese) before entering duction. A woman said, there is little a wo the husbands house on the night of her wed man can do about child bearing. All decisions ding to ward off all the attacks of the enemy belong to our husbands. In this culture, men Christian and Muslim leaders share this view are to be heard even when they are not the but both differed on the ritual as solution. Closely related rated this view saying, children belong to the to this is that participants argued that a wo father in this culture. It will be an aberration man may suffer infertility if she acts against a for a woman to take absolute decision about taboo of her husbands family or that of her children. Ac expected is considered to be weak or char cording to the woman, if a woman does not med by his wife. In fact, the herbalist was of pay good attention to the taboos of her hus the opinion that if nothing is wrong with a bands house she may have problem of infer man spiritually, the wife should not be play tility. When this happens, the mans family should That is why one must enquire very well about respond to rescue their son. However, some the family of her/his spouse before going respondents felt that women should play deep into relationship. Lastly, it was a common child bearing because they are at the receiv opinion that a woman may not be able to ing end when things are not working well like bear children if she has committed abortion the case of infertility. I dont think that it is good for men to feel that Value of children is another cultural issue they have absolute decision making about mentioned by a majority (90%) of the partici African Journal of Reproductive Health Jun 2010; 14(2): 122 Yoruba Culture and Acceptance of Assisted Reproductive Technologies pants. According to a woman, marriage is challenges that may arise from the use of for children. A man indicated that question the following issues were mention one child is enough to sustain a marriage. This means who is stig was not clear who among the couples should matized or discriminated against. There participants, bareness is abhorred and unde was a general consensus among the respon sirable. A case study summarizes the find dents that husband should initiate discussion ings highlighted above. According to a wife this is a sensi tive issue to discuss by any woman suffering Case Study from infertility. It is better to allow such a discus Mr and Mrs A, aged 48 and 34 year respec sion to come from the man himself. The couple did was corroborated by a male participant say all it takes to have a child of their own but no ing It is not a good thing for a woman to ini luck. Husband is the head gyneacologists several times without positive of the family and he should be the one to say result. We cologists and the Nurses were of the opinion have tried to sustain our faith as Christians that such a discussion should be done jointly but temptation kept on coming. Family pressures the couples interviewed said that they have kept on coming from right and left with sug never done so. The prayer exposed wo ness on the part of both the wife and hus men to ridicule as if the problem of bareness band. Despite the prayers and all blem would try to proof that he or she is able efforts there was no pregnancy. Similarly, a wife indicated of adoption but we dumped it because of that such an issue is not easily discussed by societal reaction. Husband sug husband and wife will continue to seek solu gested the option and it was jointly decided tion to proof themselves. We tried to keep it this may lead to extra marital affairs espe from family members. For the community members, it is not something that should be discussed because Respondents were asked about the ethical the culture does not support it. Most women do come pondents were of the view that such a child down with this problem often especially may not enjoy equal recognition as those where husbands feel that they are not the born through the natural process. For the nurse, it to a wife, the best thing is that people should usually results in low self esteem within the not know. It is difficult to hide such a thing in marital union and in the immediate com our society where everybody is part of the munity. An adult male community member these include physical, social and psycho indicated that the issue of paternity is very logical injuries that may arise from the use of important in this culture. It was argued that error may occur in ple should have a child outside the natural the process of the operation. For many res process such a child may have problem of pondents, this may lead to permanent defor identity in the extended family and the so mity on the part of both the wife and the ciety may look at such a child with reserva husband. It is not a good experience to polygamous union, such a woman will be a be childless because one will go through se laughing stock and the child may be denied veral trials hoping to get solution from them. The There is nothing as good as natural process message that is giving is that the woman is of child bearing. This view was sup because they are to carry the pregnancy and ported by both Christian and Muslim priests one is not sure that such a process cannot both of who are of the opinion that the right lead to complications. This raises the question about may not be happy because they know that the cost and accessibility of the technologies. Respon that such a child may not receive equal love dents were of the view that the husband if eventually the father has children from should be the one to pay for it since he is the other women. This raises the question by a male community member saying that of how readily are the husbands willing to some men do have children through other pay for this kind of service. A African Journal of Reproductive Health Jun 2010; 14(2): 124 Yoruba Culture and Acceptance of Assisted Reproductive Technologies female respondent was of the view that as Kinship is the organizing principle of so long as the cost of receiving the service is ciety. It stipulates relationship, marriage choi high and the cause of infertility is still asso ces and family patterns. It is the basis of eco ciated with women it will be difficult for fami nomic, religious and political organization as lies to use it. Therefore, it will be dif are mostly affected do not have enough re ficult to understand who should be involved sources to demand for the service. This was in decision making about a patient without corroborated by a husband who argued that understanding the kinship system. So also, women have no right to make such decision cultural practices must be understood in re alone without involving the husband who will lation to the individual patient. Many women cannot afford the instance, provide some security and some cost of such services. Even if they can afford supra-individual means for taking action it the culture does not permit them to do so. Con autonomy, rights and dignity of users are fession, by the wrongful acts of the self are major ethical challenges in patriarchal socie made present to it and to the community, is ties where male dominance is the order of therefore often part of Dinka way of dealing the day. Knowledge is power, where this in patriarchal societies where female gender lack of cultural beliefs and religious injunc cannot take independent decision is a major tions tend to fill the gap. African Journal of Reproductive Health Jun 2010; 14(2): 125 Yoruba Culture and Acceptance of Assisted Reproductive Technologies It has been argued that misrepresentation that resulted in this paper. The authors de caused by lack of cultural sensitivity and clare no conflict of interest. Task Force on diagnosis and treatment of can lead to litigation which may disrupt physi infertility, infections, pregnancy and infertility. Approaches to the control of and practices thereby constituting major ob sexually transmitted infections in developing countries: old problems and modern challenges. Even Sexually Transmitted Infections, 2004, 80: 174 though some individuals may not have pro 182. Widge A, Sociocultural attitudes towards infertility while setting up infertility research in non and assisted reproduction in India. London, Taviskos ual indices of the phenomenon due to varied 1951 conceptualization. Ayantayo K, African Traditional Ethics and red their time to participate the interviews Transformation: Innovation And Ambivalence African Journal of Reproductive Health Jun 2010; 14(2): 126 Yoruba Culture and Acceptance of Assisted Reproductive Technologies Involved, And Modification Necessary For Sound 23. Correspondence: Thaleia Basmatzoglou, Student of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, Greece. They are directly connected to each other owing to the impact of this metabolic disease in humans reproductive function. Objective (Aim): this study aims to draw the attention of diabetes mellitus, both type 1 and type 2, in males and females in relationship to infertility.

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