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Accessible and inaccessible: A patient is said to medicine 94 generic mentat 60caps with visa be accessible if the psychiatrist or analyst succeeds in making rapport with him medicine sans frontiers buy generic mentat 60 caps on-line, and inaccessible if he fails treatment vaginal yeast infection buy genuine mentat. The term is pseudo-objective treatment 4 hiv order 60caps mentat with visa, since it implies that the capacity for rapport is a constant, identical in every examining physician. Accident proneness: Susceptibility to accidents based on psychological cause or motivations. Acetylcholine: A neuro-transmitter which is particularly found at the mo to r end plate and is therefore involved in muscle action. Used particularly to refer to real life successes and when evaluating a persons life. Achievement motivation: the motivation to accomplish valued goals and to avoid failure. This concept became important as motivation theory became less dominated by physiological drives. Achievement test: Tests used to measure present knowledge or skills especially knowledge or skills developed through specific learning. Acquisition: (1) A term used to indicate that a particular skill or ability has been gained by an animal or human being. When applied to language, this term is used to avoid drawing inferences about whether language has been learned or inherited. Acquisition curve: the graphic representation of learning which shows that the strength of the learned response gradually increases with more and more learning trials. Acting out: To express a wish, need or motivation particularly when it is unrecognized or unconscious in overt behaviour rather than words. Often the behaviour is aggressive and self-destructive and may be very unchar acteristic for the persons who may have no idea, why they behave in that way. In psychoanalysis, the essence of Dictionary of Psychology & Allied Sciences 7 concept is the replacement of thought by action and it implies that (a) the impulse being acted out has never acquired verbal representation, or (b) the impulse is to o intense to be dischargeable in words, or (c) that the patient lacks the capacity for inhibition. Since psychoanalysis is a talking cure carried out in a state of reflection acting out is antitherapeutic. Acting out is characteristic of psychopathy and behaviour disorders and reduces the accessibility of these conditions to psychoanalysis. Action theory: A theory concerned with the study of human goal directed behaviour and its social basis. Active and passive: Friend made extensive use of the idea that there exists a polarity between activity and passivity; Masculinity, aggression, sadism and voyeurism being active and feminity, sub missiveness, masochism and exhibitionism being passive. The situation is, however complicated by a further assumption that instincts can undergo reversal in to their opposite, in particular that active instincts can become passive, sadism and voyeurism being usually cited as the examples of instincts capable of this reversal. Active group therapy: A type of group therapy introduced and developed by S R Slavon and designed for children and young adolescents, with emphasis on emotional and active interaction is a permissive, non-threatening atmosphere. The therapist stresses on reality testing, ego strengthe ning and active interpretation. Active therapist: Type of therapist, who makes no effort to remain anonymous but is forceful and expresses his personality definitively in the therapy setting. Act psychology: the origin of the concept lie in Brentanos doctrine of intentionality. It asserts that mind could not be reduced to a set of elements 8 Dictionary of Psychology & Allied Sciences found in consciousness. It is the way in which that activity contains or is directed to wards that result which manifests the true nature of mind not the results alone. Actual neurosis: Friend, in his early writing, distin guished between psychoneuroses and actual neuroses, the former being due to psychological conflicts and past events the latter being the physiological consequences of present distur bances in sexual functioning. He further distin guished two forms of actual neurosis; neurasthenia, the result of sexual excess and anxiety neurosis, the result of unrelieved sexual stimulation. Actualizing tendency: A term coined by Rogers (1954) to describe the process by which people seek to develop their various potentials and maximize their personal growth. Acute confusional state: (1) A form of delirium in which the most prominent symp to ms are disorders of memory deficit and both retrograde and antero grade amnesia and clouding of consciousness (reduced clarity of awareness of environment and reduced capacity to shift, focus and sustain attention to environmental stimuli). The reaction is characterized by frustration; rage, inability to concentrate and feeling or estrangement, depersonalization, and loneliness; it is generally self-limited and subsides and the person adjusts to his situation. Dictionary of Psychology & Allied Sciences 9 Acute reaction to stress: Very transient disorders of any severity and nature which occur in individuals without any apparent pre-existing mental disorder in response to exceptional physical or mental stress such as natural battle and which usually subside within hours or days. The acute reaction to stress may manifest a predominant disturbance of emotions. Adaptation: the process of fitting or conforming to the environment by behavioural or psychic changes that promote an optimal level or functioning. The term has highly specific meanings in, (1) physio logy the adjustment of bodily organ to particular environmental demands, (2) evolutionary biology how a species is matched to the environments in which it has developed, and (3) psychologythe process by which an individual achieves the best balance feasible between conflicting demands. In psychoanalytic view, adaptation tends to be regarded as a function which is imposed on the developing individual from without as a result of his experience of frustration. Consonant with Sandor Rados formu lations on adaptational psychodynamics, therapy focuses on the maladaptive patterns used by patients in the treatment sessions, on how those patterns developed and on what the patients must do to overcome them and stabilize their functioning at self-reliant, admit levels. Adaptive behaviour: Any behaviour that increases an organisms ability to adjust to a specific environ ment or situation. Axis V, is the clinicians determination of the patients highest level of adaptive functioning in the previous year. Addiction: A state of physiological or psychological dependence on some substance, usually a drug, resulting in to lerance of the drug such that progressively larger doses are required to obtain the same effect. Addictions are most clearly identified by a failure to function adequately when the substance is withdrawn. The commonest addictions are of socially accepted drugs such as nicotine and alcohol, though illegal drugs. Colloquially the term has been stretched to cover need which have become exaggerated to a degree, that is damaging the individual. Adjustment: Functional, often transi to ry, alteration or accommodation by which one can better adapt oneself to the immediate environment and to ones inner self. Also defined as a judgement heuristic in which subjective probability estimated at a certain point and are raised or lowered depending on the circumstances. Adjustment disorder: Mild and transient disorders lasting longer that acute reactions to stress, which occur in individuals of any age without apparent pre-existing mental disorder. Such disorders are often relatively circumscribed or situation specific are generally reversible and usually last only a few months. They are usually closely related in time and content to stresses such as bereavement. The Dictionary of Psychology & Allied Sciences 11 symp to ms generally lessen as the stress diminishes or as the person adapts to the stress. Adler, Alfred (18701937): Viennese psychiatrist and one of Freuds original followers. Adler broke off from Freud and introduced and developed the concepts of individual psychology, inferiority complex, overcompensation and masculine protest. Administrative psychiatry: the branch of psychiatry that deals with the organization of the efforts of many people in clinical practice, in a programme or in a hospital or other facility to provide care and treatment. Its focus is on the management process formed by the interaction of health administration, clinical care of psychiatric patients, programme elements and the mental health organization itself with the attitudes, values and belief systems of the environment in which the structure exists. The beginning of secondary sexual characteristics, usually at about 12, and the termination of adole scence is marked by the achievement of sexual maturity at about age 20. Research on adolescence has tended to emphasize the four developmental areas of com petence, individuation, identity and self-esteem. Adorno: Born Theodor Wiesengrund in Frankfurt at Main, Adorno (19031969) was a German Jewish Philosopher, an outstanding neo-Marxist intell ectual and a founding father of the Frankfurt school. He made important contributions to musicology, aesthetics, sociology and social psychology. Adrenaline: A sympathomimetic catecholamine formed from noradrenaline and the major hormones secreted by the adrenal medulla. Its release during states of fear or anxiety produces many of the physio logical changes associated with those emotions. The reference is usually to theories about the psychology of infants which the speaker believes overestimate their level of development.

A 72-year-old male patient with a diagnosis of Parkinson disease said everlast my medicine discount mentat 60caps on line, Im star medicine ball exercises cheap 60 caps mentat free shipping, star symptoms xanax treats buy generic mentat 60 caps on-line, start ing to treatment using drugs cheap mentat 60caps on line think of mo, mo, mo, moving house. Although it looked normal, she said that she hated it and had always wished that it was different in size, shape and feel. A 27-year-old male patient presented with a longstanding belief that his face was ugly, in particular his nose that he thought was far to o large and crooked. A 40-year-old female patient presented with the complaint that she could continue to feel her to othbrush in her hands for up to 15 minutes after she used it. An 8-year-old male patient presented with a his to ry of heightened startle refex characterized by eye blinking, head fexion, abduction of the upper arms, movement of the trunk and bending of the knees in response to a loud noise. A 40-year-old female patient with a his to ry of recurrent depression, and currently depressed, gave a his to ry of inability to experience pleasure in her usual hobbies and interests as well as a general inability to experience any feeling. A 75-year-old male patient with a diagnosis of Parkinson disease spoke in a mono to nous voice. In addition he seemed not to recognize the emotional meaning of variations in to ne of voice. A 23-year-old female patient presented with excessive fear, self-consciousness and avoidance of social situations due to the possibility of embarrassment or humiliation. A 27-year-old male accountancy trainee presented with a his to ry of repetitive and intrusive thoughts about cleanliness and hygiene, which were associated with increasing tension and worry, and which he recognized as his own thoughts. He tried to resist these thoughts, but found that they became even more urgent and intrusive. A 32-year-old female patient, who had recently given birth, presented with a six week his to ry of temper outbursts, feelings of hostility to wards her husband, an unpleasant feeling of distress and impatience with her children. A 21-year-old male recently diagnosed with schizophrenia and treated with risperidone com plains of mo to r restlessness, inner agitation and an inability to sit still. A 17-year-old male patient is brought to the attention of his general practitioner because he newly recognized a problem with gambling, drinking excessively and misusing cannabis. A 21-year-old male patient presented with a his to ry of episodes of excessive sleeping (amount ing to up 15 hours a day), excessive eating, increased sexual libido, low mood and transient persecu to ry beliefs. A 28-year female patient presented for the frst time with markedly slowed movements, some times resulting in immobility, strange postures and muteness. On examination she allows her upper limbs to be put in uncomfortable postures that she holds for long periods of time. On examination she does not know the date, day, time, season, place where she is and her own address. An 18-year-old male patient presents with a his to ry of several and irresistible periods of drowsiness during the day. The partner of a 25-year-old male patient accompanies him to the outpatient appointment. She reports that he talks in his sleep, wanders aimlessly in the bedroom for a few minutes at night and that he has no recollection of these incidents. A 47-year-old female patient with a his to ry of recurrent depression is admitted in a mute state. He was only able to recall events that happened approximately fve minutes before the collision. A 45-year-old male patient was involved in an accident at work where he sustained a serious head injury and lost consciousness. On regaining his consciousness he could only recall events that happened approximately 36 hours after the incident. A 45-year man presents with a complaint that he frst saw a black cat at the corner where his drive joined the main street. A 19-year-old man with a recent diagnosis of schizophrenia complained that the faces of people looking at him would suddenly look different, as if they were pulling faces at him. A 25-year-old female patient with a his to ry of complex focal seizures complained of scenes and objects becoming smaller before a seizure. He reported that his father had been replaced by a robot who looked almost exactly like him but was defnitely not him. A 40-year-old female patient complained that her local priest was sending her secret messages, declaring his feelings for her. When asked the reason for this belief, she said that she had suddenly come to this realization. He then held a frm belief that he was at risk from immigrants, particularly Romanians. She was particularly distressed by the experience of having thoughts manipulated and taken from her. A 25-year-old patient said, Phlogons have invaded my lungs turning frst sideways and now medways. A 64-year-old male patient with a longstanding his to ry of schizophrenia replied to the ques tion, What have you got in your cupfi A 72-year-old male patient with a diagnosis of Parkinson disease said, Im star, star, starting to think of mo, mo, mo, moving house. A 23-year-old male patient presented with the belief that his muscles were to o small, a preoc cupation with physical build, excessive exercising and disturbed eating. A 36-year-old male patient presented to the local dental hospital with an aching pain in both sides of the lower jaw radiating to the temporo-mandibular joints and to the neck. A 75-year-old male patient with a diagnosis of Parkinson disease spoke with a mono to nous voice. A 32-year-old female patient presented with discrete episodes of intense and extreme fear. A 32-year-old female patient, who had recently given, birth presented with a six week his to ry of temper outbursts, feelings of hostility to wards her husband, an unpleasant feeling of distress and impatience with her children. A 21-year-old male recently diagnosed with schizophrenia and treated with risperidone complains of mo to r restlessness, inner agitation and an inability to sit still. In addition he is reported as prone to losing his temper and liable to say things which he later regrets. A 28-year female patient presented for the frst time with markedly slowed movements, sometimes resulting in immobility, strange postures and muteness. Cata to nia (see page 304) I N D E X Page numbers followed by f indicate fgures, t Aggression, 300301 indicate tables, and b indicate boxes. How to cite this document: Working group of the Clinical Practice Guideline for Eating Disorders. Madrid: Quality Plan for the National Health System of the Ministry of Health and Consumer Affairs. Interventions at the Different Levels of Care in the Management of 81 Eating Disorders 9. Support Associations for Patients with Eating Disorders and their Families 252 Annex 4. Pro to cols, Recommendations, Therapeutic Orientations and Guidelines for Eating Disorders 267 Annex 6. Results of the Search, Selection and Quality Assessment of Evidence based on the stages performed 269 Annex 6. To ensure that clinical decisions are appropriate, efficient and safe, health care professionals must constantly update their knowledge, an objective that entails great dedication and effort. In early 2006, the Direc to rate General of the National Health System Quality Agency elaborated the Quality Plan for the National Health System, a plan that encompasses twelve strategies. In 2007, the Health Guide project was renovated by creating the Clinical Practice Guideline Library. Eating disorders, anorexia nervosa and bulimia nervosa, as well as other similar clinical pictures, are disorders of multifac to rial ethiopathogeny that have been a great challenge for public health care in the last decades. Sociocultural fac to rs that can lead to eating disorders, as well as the serious physical, social and psychological sequelae that these disorders entail have caused great social alarm. Eating disorders are diseases that not only involve the affected individual, but also the family and closest environment, and even health care and education professionals who are directly or indirectly involved, and who have no access to guides to address these disorders successfully. Understanding and assessing these diseases, identifying them and assessing their risk potential, as well as presenting therapeutic objectives, and deciding on the best site for treatment and providing help to families, are tasks that can be tackled from different professional settings with an undeniable benefit for patients and family members.

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In: Book of abstracts of the 1st International Conference of Applied Natural Sciences, November 7 9, 2007 (pp. Lipase catalyzed irreversible transesterifications using enol esters as acylating reagents: preparative enantio and regioselective synthesis of alcohols, glycerol derivatives, sugars, and organometallics. Enzymatic transformation of flavonoids and terpenoids: structural and functional diversity of the novel derivatives. Controllable regioselective acylation of rutin catalyzed by enzymes in non-aqueous solvents. Kinetics and mechanism of synthesis of butyl isobutyrate over immobilised lipases. Mechanistically, there have been many hypotheses proposed to explain this phenomenon and two are more prominent: one is that by consuming excessive glucose, cancer cells may change the tumors microenvironment to gain growth advantage over normal cells; the second is that, to sustain a dominant glycolysis process, cancer cells alter the expression or functions of glucose metabolic enzymes, which may have resulted in additional changes that promote cancer development (Vander Heiden et al. A growing body of evidence has supported both hypotheses and will be reviewed here. Altered glycolytic enzymes in cancer cells In cancer cells, the activities or expression levels of many enzymes participating in glucose metabolism are altered, those involved in glycolysis in particular. The glycolysis commonly refers to the reactions that covert glucose in to pyruvate or lactate (Figure 1). Usually, one or more isoforms of glycolytic enzymes have altered expression patterns or activities in cancer cells, which was previously reviewed (Herling et al. It is also differentially regulated at the post-translational level in cancer cells as compared with normal cells. Five aspartate and five glutamate residues were found to be specifically methylated in pancreatic cancer. Several serine and threonine residues were found to be specifically phosphorylated in leukemia, cervix, and lung cancers. Glucose metabolic pathways switched by oncogenes and tumor suppressors It has been long proposed that the altered expression or enzyme activities of glycolytic enzymes are regulated by oncogenes and tumor suppressor genes. Therefore, activation of oncogenes and loss of tumor suppressors are believed to underlie the metabolic switch in cancer cells. Another oncogene, K-Ras, can alter glucose metabolism so as to provide tumor cells with a selective advantage. Interestingly, in these cells mi to chondrial functions and oxidative phosphorylation are not compromised, which allows increased survival rate of the K-Ras mutant cells during glucose deprivation (Annibaldi and Widmann, 2010). Tumor friendly microenvironment attributed to altered glucose metabolism One would ask: what is the advantage for cancer cells to use energy-inefficient glycolysis under adequate oxygen supply. A potential advantage, as a result of Warburg effect, is high production of lactic acid due to enhanced glycolysis. Positive correlation between lactate serum levels and tumor burden in cancer patients has been well documented, implicating a role of acidic microenvironment in promoting tumor growth and development (McCarty and Whitaker, 2011). First, accumulated evidence has suggested that acidic environment amplifies the capacity of invasion and metastasis of cancer cells. For instance, acid pretreatment of tumor cells enhance their ability to form metastases in tumor-transplanted mice (Rofstad et al. Consistently, it has been shown that increasing tumor pH via bicarbonate therapy significantly reduces the number and the size of metastases in a mouse model of breast cancer (Robey et al. Second, the extracellular pH of solid tumors is significantly more acidic than that of normal tissues, thus impairing the uptake of weakly basic chemotherapeutic drugs (Raghunand et al. Several anticancer drugs such as doxorubicin, mi to xantrone and vincristine are weak bases that are pro to nated in slightly acid tumor microenvironments. The pro to nated forms of the drugs cannot easily diffuse across the plasma membrane and therefore their cellular uptake is suppressed. It has been demonstrated that the addition of sodium bicarbonate in the drinking water enhanced the anti-tumor effect of doxorubicin on xenotransplanted tumors presumably by enhancing the intracellular drug delivery through raising the pH of the extracellular milieu in mice (Raghunand et al. The reverse situation was also demonstrated in another study showing that glucose administration to mice led to a lower efficacy of doxorubicin on tumors presumably due to a decrease in the extracellular pH (Gerweck et al. Glucose Metabolism and Cancer 295 Third, acidic microenvironment inhibits anti-tumor immune response. Activated lymphocytes themselves use glycolysis, which relies on the efficient secretion of lactic acid. Export of lactic acid from lymphocytes depends on a gradient between intracellular and extracellular lactic acid concentration. High extracelullar acidity would diminish this gradient and block the secretion of lactic acid from lymphocytes. The accumulation of intracellular lactic acid eventually disturbs the glycolysis process hence affecting the activity of lymphocytes. Acidification similarly inhibits the activity of other immune cells such as dendritic cells. Coupled biological and metabolic processes and the logic of a mammalian metabolic cycle Glycolytic enzymes have multiple cellular functions. Conceivably, the participation of these glycolytic enzymes in such a cell cycle event would subject cell cycle regulation to altered glucose metabolism in cancer cells, providing yet another mechanistic explanation of cancer growth and development. The moonlighting participation of the glycolytic enzymes in a cellular process would in theory impose a dynamic modulation of the redox status in the cellular compartment where this process is executed and subsequently affect the functions of other redox-sensitive proteins in the same intracellular compartment. The coupling of these cellular processes is apparently crucial for the maintenance of chromatin integrity during cell cycle, and thus altered glucose metabolism in cancer cells potentially would disrupt the coupling of these processes and make cancer genomes more error-prone. Upon entering S phase, the ratio becomes lower, corresponding to a reductive status. This oxidative status appears to be maintained 296 Biochemistry until cells enter the next S phase. Conceivably, if glucose metabolism is altered, the cell cycle must be coordinately modulated, and vice versa. Therefore, cancer cells may have acquired the growth and proliferative advantage over normal cells through alteration in glucose metabolism. Targeting glycolysis for cancer treatment the aberrant metabolic pathways underlying the Warburg effect are being considered as novel targets for cancer therapy. Several strategies have been employed to target glucose metabolic pathways for cancer treatment. First, inhibi to rs of glycolytic enzymes or glycolytic pathways are being searched to identify therapeutic agents that can inhibit cancer growth and development. A number of small molecules have been reported to target glycolysis although none to date has been shown to have specific molecular targets. Unfortunately, none of these clinical trials have successfully shown its therapeutic benefit in terms of time- to -progression and overall survival (Oudard et al. Encouraging preliminary results demonstrated that it is safe, well to lerated, and may offer disease control (Porpora to et al. Among them, the most potent one resulted in decreased glycolysis and increased cell death in respond to loss of growth fac to r signaling, supporting the feasibility and viability of targeting glucose metabolism as a novel strategy to treating human cancers (Vander Heiden et al. Comparing to small molecule inhibi to rs, immunotherapy offers superior target specificity and may be used as an alternative approach to target other glycolysis enzymes. Second, inhibition of glycolytic enzyme or glycolysis pathways serves as a strategy to enhance the sensitivity of tumor cells to conventional cy to to xic chemotherapy agents. The safety of using it as an anti-cancer agent has been questioned notably because of brain to xicity (Tennant et al. However, it has a proven efficacy in sensitizing human osteosarcoma and non-small cell lung cancers to adriamycin and paclitaxel (Maschek et al.

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A strong asso ciation (a large relative risk) is more likely to medicine recall purchase mentat discount indicate causality than a weak association symptoms your dog has worms generic mentat 60 caps with amex, although it is recognized that relative risks of small magnitude do not imply lack of causality and may be important if the disease is common medications qid purchase mentat now. Associations that are replicated in several studies of the same design or using different epidemiological approaches or under different circumstances of exposure are more likely to 4 medications at target discount mentat 60 caps free shipping represent a causal relation ship than isolated observations from single studies. If there are inconsistent results among investigations, possible reasons are sought (such as differences in amount of exposure), and results of studies judged to be of high quality are given more weight than those of studies judged to be methodologically less sound. When suspicion of carcino genicity arises largely from a single study, these data are not combined with those from later studies in any subsequent reassessment of the strength of the evidence. If the risk of the disease in question increases with the amount of exposure, this is considered to be a strong indication of causality, although absence of a graded response is not necessarily evidence against a causal relationship. Demonstration of a decline in risk after cessation of or reduction in exposure in individuals or in whole populations also supports a causal interpretation of the findings. Although a carcinogen may act upon more than one target, the specificity of an asso ciation (an increased occurrence of cancer at one ana to mical site or of one morphological type) adds plausibility to a causal relationship, particularly when excess cancer occur rence is limited to one morphological type within the same organ. Although rarely available, results from randomized trials showing different rates among exposed and unexposed individuals provide particularly strong evidence for causality. Such a judgement requires first of all that the studies giving rise to it meet, to a sufficient degree, the standards of design and analysis described above. Specifically, the possibility that bias, confounding or misclassification of exposure or outcome could explain the observed results should be considered and excluded with reasonable certainty. In addition, all studies that are judged to be methodo logically sound should be consistent with a relative risk of unity for any observed level of exposure and, when considered to gether, should provide a pooled estimate of relative risk which is at or near unity and has a narrow confidence interval, due to sufficient popu lation size. Moreover, no individual study nor the pooled results of all the studies should show any consistent tendency for the relative risk of cancer to increase with increasing level of exposure. It is important to note that evidence of lack of carcinogenicity obtained in this way from several epidemiological studies can apply only to the type(s) of cancer studied and to dose levels and intervals between first exposure and observation of disease that are the same as or less than those observed in all the studies. Experience with human cancer indicates that, in some cases, the period from first exposure to the development of clinical cancer is seldom less than 20 years; latent periods substantially shorter than 30 years cannot provide evidence for lack of carcinogenicity. For several agents (afla to xins, 4-aminobiphenyl, azathio prine, betel quid with to bacco, bischloromethyl ether and chloromethyl methyl ether (technical grade), chlorambucil, chlornaphazine, ciclosporin, coal-tar pitches, coal-tars, combined oral contraceptives, cyclophosphamide, diethylstilboestrol, melphalan, 8 methoxypsoralen plus ultraviolet A radiation, mustard gas, myleran, 2-naphthylamine, nonsteroidal estrogens, estrogen replacement therapy/steroidal estrogens, solar radiation, thiotepa and vinyl chloride), carcinogenicity in experimental animals was established or highly suspected before epidemiological studies confirmed their carcinogenicity in humans (Vainio et al. Although this association cannot establish that all agents and mixtures that cause cancer in experimental animals also cause cancer in humans, nevertheless, in the absence of adequate data on humans, it is biologically plausible and prudent to regard agents and mixtures for which there is sufficient evidence (see p. The possibility that a given agent may cause cancer through a species specific mechanism which does not operate in humans (see p. The nature and extent of impurities or contaminants present in the chemical or mixture being evaluated are given when available. Animal strain, sex, numbers per group, age at start of treatment and survival are reported. For experimental studies of mixtures, consideration is given to the possibility of changes in the physicochemical properties of the test substance during collection, s to rage, extraction, concentration and delivery. Chemical and to xicological interactions of the components of mixtures may result in nonlinear doseresponse relationships. The relevance of results obtained, for example, with animal viruses analogous to the virus being evaluated in the monograph must also be considered. They may provide biological and mechanistic information relevant to the understanding of the process of carcinogenesis in humans and may strengthen the plausibility of a conclusion that the biological agent under evaluation is carcinogenic in humans. Guidelines for conducting adequate long-term carcinogenicity experiments have been outlined. Considerations of importance to the Working Group in the interpretation and eva luation of a particular study include: (i) how clearly the agent was defined and, in the case of mixtures, how adequately the sample characterization was reported; (ii) whether the dose was adequately moni to red, particularly in inhalation experiments; (iii) whether the doses and duration of treatment were appropriate and whether the survival of treated animals was similar to that of controls; (iv) whether there were adequate numbers of animals per group; (v) whether animals of each sex were used; (vi) whether animals were allocated randomly to groups; (vii) whether the duration of observation was adequate; and (viii) whether the data were adequately reported. When benign tumours occur to gether with and originate from the same cell type in an organ or tissue as malignant tumours in a particular study and appear to represent a stage in the progression to malignancy, it may be valid to combine them in assessing tumour incidence (Huff et al. The occurrence of lesions presumed to be pre neoplastic may in certain instances aid in assessing the biological plausibility of any neo plastic response observed. If an agent or mixture induces only benign neoplasms that appear to be end-points that do not readily progress to malignancy, it should nevertheless be suspected of being a carcinogen and requires further investigation. Evidence of an increased incidence of neoplasms with increased level of exposure strengthens the inference of a causal association between the exposure and the develop ment of neoplasms. The form of the doseresponse relationship can vary widely, depending on the particular agent under study and the target organ. Since many chemicals require metabolic activation before being converted in to their reactive intermediates, both metabolic and pharmacokinetic aspects are important in determining the doseresponse pattern. The statistical methods used should be clearly stated and should be the generally accepted techniques refined for this purpose (Pe to et al. When there is no difference in survival between control and treatment groups, the Working Group usually compares the proportions of animals developing each tumour type in each of the groups. Otherwise, consideration is given as to whether or not appropriate adjustments have been made for differences in survival. Several survival-adjusted methods have been developed that do not require this distinction (Gart et al. The nature of the information selected for the summary depends on the agent being considered. For chemicals and complex mixtures of chemicals such as those in some occupa tional situations or involving cultural habits. Concise information is given on absorption, distribution (including placental transfer) and excretion in both humans and experimental animals. Studies that indicate the metabolic fate of the agent in humans and in experimental animals are summarized briefly, and comparisons of data on humans and on animals are made when possible. Comparative information on the relationship between exposure and the dose that reaches the target site may be of particular importance for extrapolation between species. Data are given on acute and chronic to xic effects (other than cancer), such as organ to xicity, increased cell proliferation, immuno to xicity and endocrine effects. Effects on reproduction, tera to genicity, fe to to xicity and embryo to xicity are also summarized briefly. Tests of genetic and related effects are described in view of the relevance of gene mutation and chromosomal damage to carcinogenesis (Vainio et al. The adequacy of the reporting of sample characterization is considered and, where necessary, commented upon; with regard to complex mixtures, such comments are similar to those described for animal carcinogenicity tests on p. The concentrations employed are given, and mention is made of whether use of an exogenous metabolic system in vitro affected the test result. Positive results in tests using prokaryotes, lower eukaryotes, plants, insects and cultured mammalian cells suggest that genetic and related effects could occur in mammals. Results from such tests may also give information about the types of genetic effect produced and about the involvement of metabolic activation. In-vitro tests for tumour-promoting activity and for cell transformation may be sensitive to changes that are not necessarily the result of genetic alterations but that may have specific relevance to the process of carcinogenesis. Genetic or other activity manifest in experimental mammals and humans is regarded as being of greater relevance than that in other organisms. The demonstration that an agent or mixture can induce gene and chromosomal mutations in whole mammals indi cates that it may have carcinogenic activity, although this activity may not be detectably expressed in any or all species. Relative potency in tests for mutagenicity and related effects is not a reliable indica to r of carcinogenic potency. Negative results in tests for mutagenicity in selected tissues from animals treated in vivo provide less weight, partly because they do not exclude the possibility of an effect in tissues other than those examined. Moreover, negative results in short-term tests with genetic end-points cannot be considered to provide evidence to rule out carcinogenicity of agents or mixtures that act through other mechanisms. Fac to rs that may lead to misleading results in short-term tests have been discussed in detail elsewhere (Montesano et al. When available, data relevant to mechanisms of carcinogenesis that do not involve structural changes at the level of the gene are also described. The adequacy of epidemiological studies of reproductive outcome and genetic and related effects in humans is evaluated by the same criteria as are applied to epidemio logical studies of cancer. Structureactivity relationships that may be relevant to an evaluation of the carcino genicity of an agent are also described. For biological agentsviruses, bacteria and parasitesother data relevant to carcinogenicity include descriptions of the pathology of infection, molecular biology (integration and expression of viruses, and any genetic alterations seen in human tumours) and other observations, which might include cellular and tissue responses to infection, immune response and the presence of tumour markers. Inadequate studies are generally not summarized: such studies are usually identified by a square-bracketed comment in the preceding text. Exposure to biological agents is described in terms of transmission and prevalence of infection.

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