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There is also some evidence that epigenetic changes might occur in response to maternal overnutrition [50 purchase genuine valtrex on line,51] cheap generic valtrex canada. Altered epigenetic regulation can be induced by both maternal under- and overnutrition within genes that control lipid and carbohydrate metabolism and within genes involved in the central appetiteeenergy balance neural network [51] cheap valtrex 500mg otc. Perinatally acquired microstructural and epigenomic alterations in regulatory systems of metabolism and body weight seem to be critical discount 500mg valtrex mastercard, leading to a cardiometabolic risk disposition throughout life [54]. People with high birth weight also were shown to have higher death rates from both prostate cancer and breast cancer in adulthood [55e57]. Intrauterine exposure to the high levels of growth hormones was initially proposed as an underlying mechanism, increasing both cell proliferation and birth weight and predis- posing to cancer in later life [57]. Both human and animal evidence suggest that exposure to obese intrauterine environment can epigenetically program the offspring obesity risk by inuencing appetite, metabolism, and activity levels [59,60]. Given that lipids act as both transcriptional activators and signaling molecules, excess fetal lipid exposure may regulate genes involved in lipid sensing and metabolism through epigenetic mechanisms [61]. Prenatal overnutrition and maternal antibiotics, as well as low physical activity during pregnancy can result in fetal macrosomia (larger than normal fetal size and weight). Fetal macrosomia-related epigenetic reprogramming causes increased anabolic hormone levels, decreased catabolic hormone concentrations, and up-regulation of adipogenic genes. Fetal macrosomia is associated with long-term health problems including some cancers and probably type 2 diabetes. Crucial to proper infant growth and develop- ment is the placenta, and alterations to placental gene function may reect differences in the intrauterine environment which functionally contribute to infant growth and may affect the consequent health outcomes. Such a programming effect of milk intake in early life could potentially have implications for cancer and ischemic heart disease risk many years later. Different gestational dietary stressors (undernutrition, overnutrition, or a modied supply of key nutrients) can elicit similar metabolic responses in offspring [9]. High carbohydrate/protein ratio in the maternal diet was shown to be linked to impaired glucose homeostasis and raised blood pressure in offspring [89,90]. The authors suggested that a high carbohydrate intake in early pregnancy suppresses placental growth, especially if combined with a low dairy protein intake in late pregnancy, and such an effect could have long-term consequences for the offsprings risk of cardiovascular disease [91]. While the molecular basis of prenatal nutritional programming is unknown, available animal and human data suggest that epigenetic changes in gene expression play a substantial role in the link between the maternal diet, and altered metabolism and body composition in the adult offspring [93e95]. According to the epigenetic programming hypothesis, suboptimal maternal diet induces epimutations in offspring during early embryonic development, and that altered expression of affected genes is maintained into adulthood, eventually affecting health [9]. Epigenetic mechanisms play a key role in mediating between the early-life nutrient inputs and the ensuing phenotypic changes throughout the entire life and seem to be responsible, in part, for the biological changes that occur during aging [96]. In animal models, maternal diet alters offspring body composition, accompanied by epige- netic changes in metabolic control genes. Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. According to this hypothesis, undernutrition during in utero development results in long-term adaptive changes in glucoseeinsulin metabolism (including reduced capacity for insulin secretion and insulin resistance) that, due to an enhanced ability to store fat, improves survival under postnatal conditions of nutritional deprivation. If mismatch exists between the environment predicted in utero and the actual environment experienced in subsequent life (e. Fetal growth restriction followed by rapid weight gain during early infancy (catch-up growth) has also been proposed to play an important role in promoting central adiposity and insulin resistance [99]. Epigenetic regulation of gene expression is one mechanism by which genetic susceptibility and environmental insults can lead to type 2 diabetes. Recently, Reinhard Stoger used elements of the thrifty phenotype and thrifty genotype concepts to synthesize a thrifty epigenotype hypothesis [101]. According to Stogers visual metaphor, the efciency of anabolic metabolism (metabolic thrift) is built upon large gene networks that form a rigid canal. In the absence of nutritional extremes (either over- or undernutrition), metabolism develops into the healthy norm. However, under conditions of intrauterine malnutrition, compensatory epigenetic changes can be induced in adipogenic and energy metabolism gene networks, and this can change the shape of the canal in such a way that metabolic phenotype is optimized for survival in these conditions. If the thrifty epigenotype 553 hypothesis is correct, then the thrifty epigenotype is anticipated to be present at signicantly higher frequencies in human populations experiencing recurrent food shortages [101]. Individ- uals exposed to these conditions will have a characteristic epigenetic prole, which could differ markedly from those for residents of developed countries. Leptin is thought to be one of the best thrifty gene candidates since it encodes a hormone regulating appetite and energy homeostasis [101]. Leptin is secreted by adipocytes, and serum leptin level is thought to signal nutritional status to the hypothalamus and thus help govern appetite and energy expenditure. Leptin has been shown to be implicated in nutritional programming during fetal and neonatal growth with long-term effects on susceptibility to obesity, diabetes, and coronary heart disease [102]. The failure of elevated leptin levels to suppress feeding and mediate weight loss in common forms of obesity denes a state of so- called leptin resistance. The mechanisms underlying leptin resistance remain a matter of debate, but there is increasing evidence that it may be programmed during the fetal and neonatal life [103]. The promoter region of the leptin gene is methylated in somatic tissues of human and mouse and displays epigenetic variation [104], and it is the gene for which proximal promoter demethylation has been shown to induce its transcription in mature adipocytes [105]. Recently, new evidence of the key role of leptin in epigenetic programming of human metabolic disorders was obtained. The strong evidence linking early-life conditions with adult disease risk has been accumulated from natural experiments, i. The bulk of these data were obtained in observational cohort studies of the long-term health consequences of the prenatal exposure to the Dutch famine of 1944e45 and to the Chinese famine of 1959e61 [107e109]. These associations were dependent on the timing of the exposure during gestation and lactation periods. The mechanisms contributing to associations between the prenatal exposure to famine and adult health outcomes are still unknown but may involve the persistent epigenetic alterations [108]. More recently, this observation was extended by the study a set of 15 additional candidate loci implicated in growth, metabolic, and cardiovascular disorders [111]. Methylation of six of these loci has been shown to be associated with in utero exposure to famine. Exposure to energy restriction during childhood and adolescence was also found to be asso- ciated with a lower risk of developing colorectal cancer. They measured maternal nutritional intake and circulating concentrations of folate, vitamin B12, tHcy, and methylmalonic acid at 18 and 28 weeks of gestation. These parameters were correlated with offspring anthropometry, body composition, and insulin resistance at 6 years. Higher maternal erythrocyte folate concen- trations at 28 weeks predicted higher offspring adiposity. The offspring of mothers with a combination of high folate and low vitamin B12 concentrations were the most insulin resistant. The early-life dietary manipulation of methyl group donors (either deciency or supple- mentation) can have a profound impact on the gene expression prole and, consequently, on the homeostatic mechanisms that ensure the normal course of physiological processes [117]. Methylation patterns in P2 of maternal blood were associated with serum levels of vitamin B12 in mothers blood, exposure to passive smoking, and mothers weight gain during pregnancy. The long-term effects of maternal behavior on the stress responsiveness and behavior of the offspring during adulthood are well documented in animal models, and these experimental ndings have been extended to humans by identifying an association between early-life adversity and epigenetic marks in adult life [133,134]. To test the hypothesis that epigenetic differences in critical loci in the brain are involved in the pathophysiology of suicide, McGowan et al. Suicide subjects were selected for a history of early childhood neglect/abuse, which is associated with decreased hippo- campal volume and cognitive impairments. The glucocorticoid receptor 1F expression was signicantly lower in samples from suicide victims with a history of childhood abuse compared with suicide victims without childhood abuse or controls. It is known that cesarean section can cause more severe stress in newborn infants compared with that of those born by vaginal delivery, who adapt to the new conditions better. To study whether the mode of delivery affects epigenetic activity in newborn infants, Schlinzig et al. The exposure to excess glucocorticoids in early life can permanently alter tissue glucocorticoid signaling, and these effects may have short-term adaptive benets but increase the risk of later disease [129]. Currently, multiple courses of synthetic glucocorticoids are recommended for various condi- tions. However, despite the benecial therapeutic effect of antenatally administered glucocorticoids, their prenatal administration can result in transgenerational effects with respect to the risk of developing several metabolic and cardio- vascular disorders in later life which implies that these epigenetic effects can persist across generations [132,136].

After well over 1 year purchase valtrex 500 mg overnight delivery, the injured person had pain in his right elbow and was diagnosed by a medical specialist with right-sided tennis elbow order valtrex. The work required pressure on the knife while turning the forearm cheap valtrex 1000 mg fast delivery, and the movements can therefore be characterised as strenuous and relevantly stressful for the development of right-sided tennis elbow buy valtrex 500 mg amex. The remaining part of the working day she performed other functions, such as making sandwiches and washing up. The hard work of stirring food involved repeated movements against resistance while at the same time requiring muscular force for a substantial part of the working day, and the housekeeper had a right-sided tennis elbow in immediate connection with this work. While puttying the walls, which she did most of the time in the period in 182 question, she used a big stopping knife. The work of puttying, grinding and coating, including the puttying of large wall surfaces with the big knife, included repeated flexion and extension movements against resistance with application of muscular force. The injured person was diagnosed with right-sided tennis elbow and golfers elbow, after having performed continuous, strenuous and repeated movements that were stressful for the relevant muscle groups of the elbow region. Example 12: Recognition of golfers elbow (machine engineer for 3 months) The injured person worked as a machine engineer in a foundry manufacturing metal bars. The work of tightening and loosening the hand wheels of the machine was strenuous and straining on the elbow since a great deal of muscular strength was needed for the twisting movements. The injured person developed a golfers elbow in good time correlation with the strenuous exposure. Example 13: Recognition of tennis elbow (industrial lacquerer spray painting for 1. The work mainly consisted in spray painting various large units with a spray pistol. The hose of the spray pistol was about 10 metres long, and the weight of the pistol alone was about 7-8 kilos. He held the spray pistol fixated in his right hand with a strenuous static grip, while at the same time pressing his thumb against the tap, spraying the units. The industrial lacquerer performed spray painting with a spray pistol, and the work involved static fixation of pistol and hose in a fixated working posture under simultaneous, stressful application of muscular force. There is good correlation between the described work exposures, in the form of a continuous, static and strenuous load on relevant muscle groups, and the development of an elbow disorder. Example 14: Recognition of golfers elbow (fish cutter for 2 years) The injured person worked in the fish industry cutting different fish. The fishes were crudely cut on a machine, and she then made filleting, and cut off fins and tail etc. According to the specialist of occupational medicine, the work was done at a relatively high pace with simultaneous twisting and flexion/extension movements of the right wrist, and partly of the elbow joint, and required some muscular force against resistance. She developed pain in her right arm after well over 2 years work, and the medical specialist made the diagnosis of right-sided golfers elbow. It was relatively high-repetitive cutting work, with simultaneous strenuousness against resistance and twisting movements as well as flexion/extension movements of wrist and elbow. This type of work is relevantly stressful for the development of a right-sided golfers elbow. Example 15: Recognition of tennis elbow (employed in a cheese dairy for 3 years) A woman worked in a dairy, picking out and cutting cheeses. The first 3 years the work consisted in cutting three-kilo cheeses with a string, and then the cheeses were placed in a machine that cut them in triangles. The cheeses were now taken from the shelves in 183 packets of 3 cheeses weighing 3 kilos each. The cheeses were wrapped in plastic, which had to be cut up and ripped apart with the application of great force. Then, in order to separate them, the cheeses were banged against the table top with some exertion. Altogether, she performed relevant elbow-loading work movements for more than half of the working day for a bit more than 3 years. Example 16: Recognition of tennis elbow (cleaning work for 3 years) A 55-year-old cleaner worked full-time in a printing shop for 3 years. She washed floors for approximately 3 hours a day and stairs for approximately 30 minutes; vacuum cleaned for about 1 hour, wiped off tables for about 1 hour and washed toilets for about 2 hours. When washing tables and toilets she wrung a cloth several times per minute, using strenuous wringing and turning movements of elbows and wrists. The toilets were often very dirty, and she had to use a lot of force to scrub them clean. Towards the end of the period she developed pain in her right elbow and a medical specialist diagnosed her with a right-sided tennis elbow (epicondylitis lateralis humeri dxt. The cleaner has had strenuous, repetitive and awkward work movements in her right elbow in connection with wet mopping and washing of stairs for a total of approx. In addition she also had powerful stresses on her elbow in connection with numerous wringing movements every day. These stresses are equivalent to 3-4 hours per day and existed for 3 years up to the onset of the disease. Example 17: Recognition of golfers elbow operator in aluminium business A 53-year-old woman worked for 4 years as a machine operator for a large manufacturer of aluminium profiles. She grabbed profiles that were 6 metres long and weighed between 3 and 30 kilos (typically 6-10 kilos) from a pallet and pulled them over to the saw, where she positioned them. The units were typically cut into 4 pieces, which she then picked up and packed into bundles, 3- 4 together. Then she lifted them onto a table and blew them clean with an air pressure pistol. She typically produced 70-80 units an hour with typically a total of approximately 300 lifts at 3/4 arms length. She developed pain in her right forearm and was diagnosed with right-sided golfers elbow. The right-sided golfers elbow qualifies for recognition on the basis of the list. This is because the work as an operator of a cut-off saw for several years constituted slightly to moderately strenuous and repetitive work for the right elbow with several hundred lifts per hour of objects weighing typically 6- 10 kilos. The work furthermore involved awkward movements of the right elbow with twisting and turning. The work with the wet mop in particular was relatively heavy and strenuous for her right arm. Only the work with the wet mop can be characterised as relevantly strenuous for the right elbow, whereas the other work functions, including the work with the dry mop, involved very moderate exertion of the elbow. Altogether the use of the wet mop was estimated at one hour per day and, for a brief period of time, about one more hour or a total of 2 hours per day. Therefore she does not meet the requirement for a relevant exposure of the right elbow for at least half of a normal, full working day (3- 4 hours) for a considerable period of time. Example 19: Claim turned down right-sided tennis elbow (butcher and bodybuilder) A 29-year-old butcher worked for a few weeks on a slaughter chain in a big slaughterhouse. His work consisted in cutting out back pieces with his right hand (the knife hand). After a short while he developed pain in his right elbow region and was diagnosed with right-sided tennis elbow. It also appeared from the information of the case that for about 2 months up to the onset of the complaints he had been in intensive hormonal treatment, being a bodybuilder in his spare time. The right-sided tennis elbow does not qualify for recognition on the basis of the list. For a short period of a couple of weeks, the work as a butcher was relevantly strenuous, repetitive and awkward for his right elbow, but in this case it is likely beyond reasonable doubt that the right-sided tennis elbow was caused by the intensive hormonal treatment. This is because the hormonal treatment in question is known to cause a massive build-up of the muscles, which very frequently has consequences, such as a tennis elbow. Therefore the disease must very likely have been caused by other than occupational circumstances, cf. Example 20: Claim turned down tennis elbow (postal worker for 2 years) A postal worker had worked for 2 years sorting letters, newspapers, magazines and small packages. The work as a mail sorter has not involved any twisting or turning movements in the elbow joint, movements against resistance or static fixation of objects with simultaneous use of muscular force, and the working postures cannot besides be regarded as awkward. The injured person therefore does not meet the requirements with regard to strenuous, elbow-straining work. Example 21: Claim turned down bilateral tennis and golfers elbow (healthcare assistant) The injured person developed complaints in both elbows after having worked in healthcare for approximately 25 years. In the period 1975 till 2004/2005, the injured person worked as a healthcare 185 assistant.

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Recently buy valtrex without prescription, a novel mechanism of eosinophil function in innate immunity has been reported discount 500 mg valtrex with mastercard. In addition buy genuine valtrex line, eo- sinophils play an important role in repair and remodelling processes as well as in immuno- modulation (Jacobsson et al order valtrex cheap. The role of eosinophils under pathological conditions has mostly been studied in parasitic infections and in bronchial asthma. Because of its cat- ionic nature, it afects the charge of surface membranes resulting in disturbed permeabil- ity, disruption and injuring of cell membranes (Kroegel et al. Depending on the tissue and infammatory response, eosinophils modulate and / or sustain either T helper 1 508 Dagmar Simon and Hans-Uwe Simon %. Eosinophils migrate through the basement membrane and can be detected in newly formed blisters afer 12 to 24 hour (Iryo et al. Eosinophil gran- ule protein depositions have been observed in both blistering and evolving lesions (Bor- rego et al. Eosinophilic spongiosis can be observed in early pemphigus including pemphigus fo- liaceus (Brodersen et al. Although eosinophils are a common feature in cutaneous drug reactions, the presence of eosinophil spongiosis may not discriminate drug-induced pemphigus from pemphigus vulgaris (Landau, Brenner, 1997). Complement fxing antibodies were shown to in- duce eosinophil infltration in pemphigus (Iwatsuki et al. Charcot-Leyden crystals that are derived from eosinophil granule proteins have been observed in pemphigus vege- tans (Kanitakis, 1987). Although neutrophils and leukocytoklasis are typical for dermatitis herpetiformis, oc- casionally undermingled eosinophils can be seen in the papillary dermis (Blenkinsopp et al. Furthermore, both neutrophils and eosinophils are the predominant infl- trating cells in linear IgA bullous dermatosis (Caproni et al. Tey inhibit cytokine and chemokine release of infltrating immune cells, in particular T cells, as well as resident cells and thus decrease the production, activation and survival of eosinophils. However, long-term corticosteroid therapy is accompanied by a number of side efects, which might be relevant in particular in elderly patients. Terefore, specifc targeting of cells and/or cytokines relevant in the pathogenesis of autoimmune bullous diseases is a promising approach. It drastically decreases eosinophil numbers in the peripheral blood and to some extent in the tissues (Pltz et al. Blocking chemokines and its receptors represents another approach to downregulate eosinophil infammatory responses. Eotaxins are chemokines that are involved in eosino- phil recruitment into the tissue and remodeling. However, the exact mechanisms how eosinophils are recruited and activated as well as their pathogenic role is not fully under- stood. The detectable eosinophil granule proteins and cytokines point to the possibility that eosinophils play a role in tissue damage, immunomodulation and/or remodeling. It should be noted, however, that the pathogenic role of eosinophils in autoimmune bullous diseases remains unclear. Clinical trials with novel drugs that specifcally target eosino- phils, cytokines or their receptors may provide new insights into the pathogenesis of these diseases, besides the analysis of clinical efcacy. Clin Exp Dermatol 24:213225 Brodersen I, Frentz G, Tomsen K (1978) Eosinophilic spongiosis in early pemphigus foliaceus. Am J Respir Cell Mol Biol 15:3544 Czech W, Schaller J, Schpf E, Kapp A (1993) Granulocyte activation in bullous diseases: release of granular proteins in bullous pemphigoid and pemphigus vulgaris. Clin Exp Allergy 38:709750 Iryo K, Tsuda S, Sasai (1992) Ultrastructural aspects of infltrated eosinophils in bullous pemphig- oid. J Dermatol 19:393399 Iwatsuki K, Tagami H, Yamada M (1983) Pemphigus antibodies mediate the development of an infammatory change in the epidermis. J Allergy Clin Immunol 113:3037 Kroegel C, Costabel U, Matthys H (1987) Mechanism of membrane damage mediated by eosino- phil major basic protein. Allergy 59:793805 Landau M, Brenner S (1997) Histopathologic fndings in drug-induced pemphigus. Early clini- cal appearance as dermatitis herpetiformis with eosinophilic spongiosis. Blood 79:31013109 Scepek S, Moqbel R, Lindau M (1994) Compound exocytosis and cumulative degranulation by eosinophils and its role in parasite killing. Gut 59:2130 Strohal R, Rappersberger K, Pehamberger H, Wolf K (1993) Nonbullous pemphigoid: prodrome of bullous pemphigoid or a distinct pemphigoid variant? Paraneoplasias (paraneoplastic signs, syndromes or diseases) are accessory expressions of malignancies which are neither caused directly by the primary tumor itself nor by metas- tases, but represent distant efects of the neoplastic process. Paraneoplasias are a time-honored concept which were frst put forward by the neu- rologist Denny-Brown (Denny-Brown, 1948) and readily accepted by dermatology. Para- neoplasias attracted attention not only because of their potential to provide insight into tumor biology but also because they might make possible the earlier detection of malig- nant tumors. In the past decades, we have witnessed an enthusi- asm in dermatology to unveil new paraneoplasias which led to an undue expansion of this disease group and to a blurring of the concept. By defnition, the malignancy is the cause of paraneoplasias, and it is not reasonable to use this term for diseases in which malig- nant tumors may arise due to the disease proper or to common underlying pathomech- nisms. So, dermatitis herpetiformis is not a paraneoplasia even if lymphomas of the bowels may arise in the setting of gluten sensitivity. So, Bowens disease is not, although it may be accompanied by internal malignancies it is not caused by 518 Peter Fritsch these. Pagets disease of the nipple is not, because it represents the cutaneous extension of an underlying mammary duct carcinoma. Simple signs, particularly if nonspecifc, are not good candidates for the paraneoplasias, though they are clearly a valuable help for being aware of internal cancer in the manage- ment of skin patients. So, pseudoichthyosis is associated with many diseases leading to malnutrition, including some neoplasms. Interestingly, hirsutism accompanying ovarian carcinoma has never been included in the paraneoplasia group. Associations which lack a certain degree of statistical likelihood should not be called paraneoplasias. Skin signs which per se may be found both in malignant and non-malignant dis- ease pose the problem of specifcity. So, it is ofen stated in reviews that hypertricho- sis lanuginosa acquisita is a paraneoplasia in close to 100% although up to 10 non- malignant conditions are ofen listed in which excessive hair growth may occur as well. For paraneoplasias, it is obviously the core problem to distinguish between causal relationship vs. Curths criteria are still cited in most reviews; however, only the statistical association and the temporal linkage of paraneoplasias and neoplasms have remained as meaningful and useful parameters. Tese purely clinical parameters are, of course, fexible and provided for a good deal of ambiguity. This should be a conspicuous and unmistakable sign, pref- erably not found otherwise in clinical dermatology a sign specifc for individual tumors or groups of tumors which arises early in the neoplastic process thus allowing timely di- agnosis and treatment. This is the case in some instances, but in general the clinical reality difers from this idealized model: 18 Paraneoplastic Syndromes of the Skin 519 Concurrent onset. Leser-Trlat, hypertrichosis lanuginosa), or improvement sets in with delay (necrolytic mi- gratory erythema) or remains incomplete (acanthosis nigricans). Nevertheless, the evaluation may be complicated by the fact that these are easy diagnoses but may also arise as non-paraneoplasias. This is best illustrated by acan- thosis nigricans which is not linked to malignancy in 80% but to up to 50 diferent non- malignant conditions, most ofen insulin resistance and obesity. Acanthosis nigricans: hyperpig- mentation, velvety surface and multiple acrochorda of the axillary fold. The presenting sign is an ill-defned hyper- pigmentation (dirty neck) in which gradually small and then larger papillomas arise, re- sulting in a velvety and then irregular texture. Histopathology shows acanthosis, papillomatosis and hyperkeratosis and (at times) increased epidermal melanin. Tere is no infammation except in lesions of the oral mu- cosa and in association with scratching. It is characterized by a difuse thickening of pal- mar skin with a prominent rugged surface texture due to disproportionately hypertrophic dermatoglyphics (tripe a simile to the corrugated mucosa of the bovine stomach). This sign is defned as the sudden and massive development of sebor- rheic keratoses which are ofen infamed and pruritic. Acquired ichthyosis is a not uncommon fnding characterized by generalized hyperkera- tosis and scaling resembling ichthyosis vulgaris.

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Because a computerized dietary assessment program is not used cheap valtrex 500mg visa, it is also difficult to calculate nutrient intakes order generic valtrex canada. Some simply present a list of common foods and ask the respondent to recall consumption of the food over the past year order valtrex from india. This permits a rough estimate of nutrient intake discount 1000 mg valtrex with visa, which may be useful in epidemiological studies in particular. Without adjustments for caloric intakes, intakes are usually grossly overestimated. There may also be biases with underreporting of socially unacceptable items or behaviors such as high-fat foods, alcohol, and so on. Food Records Food records are another method of collecting dietary intake for nutrient analysis. The individual records the brand names, cooking method, and ingredients of mixed dishes in household measurements (21). Forgetting to record intake and inaccurate estimation of volume and weights of foods and beverages are disadvantages to this method (5,21). Environmental assessment includes the identification of physical and social influences on intake. Influences in the Physical Environment on Intake Conditions within the household, access to food shopping and cooking facilities, and other factors may greatly influence intake. For those who have difficulties ambulating, the use of assistive devices should be queried because they can make the process of food preparation much easier. It may also be useful to identify the number of people in the home (5), the person responsible for purchasing and cooking food, and whether there are facilities to store and cook foods properly during periods of illness when the person may be shut in the house (5,22). Other factors to determine include whether a car is available and how far it is to the grocery or convenience store, avail- ability of foods at nearby stores, and the patients ability to commute to and transport food from the store to the home (5). An environment that promotes physical activity also contributes to nutritional status. If necessary, efforts should be made to assist a patient with applications for food assistance programs (e. Family support and frequency of communication and activity with family and friends also need to be assessed because they too can influence dietary intake (18). In scleroderma, the mouth may become small, making it difficult for patients to feed themselves and consume adequate nutrients. Generic Quality-of-Life Indicators Evaluation of quality of life includes assessing physical ability and functional activity as well as the health-related emotional and social implications. Quality-of-life questionnaires are also available specifically for pediatric or adolescent patients. The most common measures include the Childhood Health Questionnaire, Pediatric Quality of Life Inventory Scales, and Quality of My Life Questionnaire (29). Arthritis-Specic Quality of Life Disease-specific quality-of-life questionnaires have been designed for many rheumatoid diseases. Table 1 lists the disease-specific quality-of-life measures for arthritis and related diseases. They are particularly useful because they provide specific information that is directly related to the disease. Indicators of malnutrition also include rheumatoid cachexia, which involves muscle wasting that is often replaced with fat (30). Even with good disease control and adequate caloric intake, skeletal muscle catabolism persists (31,32). Assessment of caloric and protein intake is important because inadequate intakes will further accelerate muscle loss. Muscle wasting also affects functional status and mobility, which may impair food shopping, meal preparation, and cleanup. As a result of the chronic inflammation, anemia of chronic disease is often present (10,11,34). Medication-related effects on biochemical indices of folic acid and iron status are also common. Some medications such as methotrexate also affect calcium and vitamin D status (1719). Dietary and functional assessments should include attention to energy intake and problems related to obtaining, preparing, and eating food. Patients with social support may have a better quality of life, potentially moderating the impact of pain, depression, and physical disability (33). The disease is chronic and characterized by an age of onset before 16 years of joint swelling, heat, and pain and stiffness of unknown origin (10, 11) that occurs for 6 weeks or more (11). Disease characteristics often include inflammation, fever, damage/deformity of joints, and altered bone growth (10). In abnormal bone growth, one bone may be longer than another at times of accelerated growth and later become stunted. If the abnormal bone growth occurs in the leg, the child may compensate by bending the longer leg until the hips are level. Either arm-span or knee-height measurements are appropriate depending on the location of contractures and range in motion of joints. Growth charts for stature for age, weight for age, and weight for stature are important tools for monitoring growth retardation and body composition changes. Biochemical indices for iron-deficiency anemia should be monitored and assessed to determine the cause and intervention for the anemia. Side effects that affect nutritional status include mouth sores, bone marrow damage and altered iron status (10,34), and blood and protein loss in urine (34). Dietary intake and status may be influenced by many manifestations of the disease, and therefore dietary intake is important to obtain. Energy and protein malnutrition may be found in 10 to 50% of children with this disease (11). Jaw function is compromised in the 20 to 30% of children who have abnormal jaw development (10), and a small jaw or teeth misalignment can result in dysphagia (difficulty swallowing) (10,11). Patients may be depressed and embarrassed, negatively impacting their social life (10,11). Gout is more prevalent in men than women (18,19) with an age of onset after 40 years (18,35,36). Women are more likely to develop gout later in life (after menopause) than men, and the upper extremities are more often affected (35,37). Large tophi on the heels may make it difficult to accurately measure a standing height. Alternative methods of estimating height may be required depending on the manifestations of the disease. Central fat distribution may be measured using waist circumference and risk is increased with a waist circumference of more than 100 cm for men 88 cm for women (39). Patients with gout are often prescribed medications for inflammation and uric acid control. Other anti-inflammatory drugs prescribed for gout include colchicine and corticosteroids. About 80% of patients experience side effects of nausea, vomiting, and diarrhea when taking colchicine (35). Nutritional deficiency of vitamin B12, sodium, and potassium are also related to colchicine (18). Central obesity and serum uric acid levels are associated with insulin resistance, hypertension, high serum lipids, and renal failure. When gathering dietary intake data, it is important to determine intake of alcohol, nonalcoholic beverages, and purine- rich foods. Adequate hydration is important if the patient is at risk for renal calculi (18,19). Dietary intake of purine- rich foods may contribute to as much as one-third of the serum uric acid (18,19, 36,39). However, dietary intake of purine-rich foods and the impact on serum uric acid is controversial. Elevated serum uric acid is caused by inadequate renal excretion (90% of the serum level) and excess synthesis (10% (18,19,36,39)).

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