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Breaking Bulimia

Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

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Bulimia Help Method

Endorsed by University Professors, Eating Disorders Specialists, Doctors and former bulimics, the Bulimia Help Method is a proven & trusted approach to lifelong recovery from bulimia. The Bulimia Help Method home treatment program gives you the insight, skills and tools needed to break free from bulimia and to make peace with food and your body. You are guided step-by-step along the way so you always know what to expect and what to do next. A powerful audio program will help to reprogram your old eating habits at a sub-conscious level, speed up your recovery and help you feel more calm and grounded.

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Pathogenesis of Anorexia

The pathogenesis of anorexia is multifactorial and related to disturbances of the central physiological mechanisms controlling food intake. The precise neurochemical mechanisms are still matter of debate however, by understanding how energy intake is physiologically controlled, insights might be obtained. the hypothalamus transduces these inputs into neuronal responses and, via second-order neuronal signalling pathways, into behavioural responses. Intuitively, anorexia may be secondary to defective signals arising from the periphery, due to an error in the transduction process, or to a disturbance in the activity of second-order neuronal signalling pathways.

Ghrelin and Anorexia Nervosa

Anorexia nervosa is a psychiatric disorder characterised by patient-induced and maintained weight loss that leads to progressive malnutrition and specific pathophysiological signs (disturbance of body image and fear of obesity). Based on the presence or not of bulimic symptoms, anorexia nervosa appears in two specific subtypes, restricting and binge-eating purging 70 . Complications in many organ systems can occur, including cardiovascular, gastrointestinal, haematological, renal, skeletal, endocrine and metabolic systems. These alterations are not only related to the state of malnutrition, but also to the behaviour of these patients to control their weight. The endocrine disturbances include hypothalamic amenorrhoea, hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis, low T3 syndrome and alterations in the activity of the GH IGF-1 axis 71-73 . Exaggerated GH secretion coupled with reduced IGF-1 levels are common findings in anorexia nervosa as well as in other catabolic...

Appetite Loss and Anorexia

Patients receiving THC for nausea and vomiting associated with cancer chemotherapy have often shown improved appetite after receiving THC, but the effect is unpredictable (Regelson et al., 1976). In a small study comparing THC with diazepam in patients with anorexia nervosa, THC did not improve caloric intake and three of the eleven patients who took the drug developed paranoia (Gross et al., 1980). The Food and Drug Administration approved the use of synthetic THC (dronabinol) for anorexia associated with weight loss in patients with AIDS, based on clinical studies in which the effect of THC was sustained for up to 5 months a placebo-controlled trial involving 139 patients with AIDS in the US and Puerto Rico was carried out for an initial period of 6 weeks. The patients in the active arm of the trial received 2.5 mg THC twice daily before meals. THC produced a significant increase in appetite compared to the placebo but no corresponding increase in weight gain. Side effects...

Mechanisms of Cancer Related Anorexia Cachexia

The anorexia cachexia syndrome is one of the most common causes of death among patients with cancer and is present in 80 at death 1 . The term 'cachexia' derives from the Greek kakos, which means 'bad', and hexis, meaning 'condition'. The characteristic clinical picture of anorexia, tissue wasting, loss of body weight accompanied by a decrease in muscle mass and adipose tissue, and poor performance status that often precedes death has been named cancer-related anorexia cachexia (CAC) 2-5 . Since the 1980s, the previous concepts explaining CAC were replaced by a more complex insight, which stresses the interaction between metabolically active molecules produced by the tumour itself and the host immune response. One of the main features of the cachectic syndrome is anorexia, which may be so significant that spontaneous nutrition is totally inhibited. The pathogenesis of anorexia is most certainly multi-factorial but not yet well understood. It seems to be attributable, in part, to...

Cytokines in Cancer Anorexia

Cytokines play a key role in the activation of the immune system and the inflammatory response typical of the catabolic state 39-41 . Different experimental approaches have demonstrated that cytokines are able to induce weight loss. They initiate a cascade of events that ultimately leads to a state of wasting, malnourishment, and eventually death. A number of pro-inflammatory cytokines, including IL-1, TNF-a, and interferon (IFN)-y, have been isolated in tumours, as shown in Fig. 4 7 . These cytokines together with IL-6, leukaemia inhibitory factor (LIF), and ciliary neurotrophic factor (CNTF) are also implicated in the aetiology of cancer anorexia-cachexia syndrome 6,7 . A variety of tumours and peri-tumour cells release these cytokines into the circulation 42 . Elevated serum concentrations of IL-1, IL-6, and TNF- a occur in cancer patients and the concentrations of these cytokines correlate with tumour progression 4, 42, 43 . Furthermore, peripherally circulating cytokines...

The Impetus Behind Studying and Treating the Cancer Anorexia Weight Loss Syndrome

Experienced oncologists acknowledge that the cancer anorexia weight loss syndrome predicts a shorter survival for patients with advanced, incurable disease. Several powerful, well-conducted studies have borne out this clinical impression. DeWys et al. focused on weight loss in a multi-institutional, retrospective review of 3047 cancer patients and observed that loss of more than 5 of premorbid weight predicted an early demise 1 . This prognostic effect occurred independently of tumour stage, tumour histology and patient performance status. Weight loss was also associated with a trend towards lower chemotherapy response rates. Anorexia carries this same prognostic effect. Chang recently reviewed the predictive capability of various cancer symptoms and found that, similar to weight loss, anorexia, or loss of appetite, also predicts an early demise for the cancer patient 2 . Thus, the impetus for studying the cancer anorexia weight loss syndrome rests in part in the hope that effective...

Brief Overview of Mechanisms To Explain the Cancer Anorexia Weight Loss Syndrome

Recent strategies for treating the cancer anorexia weight loss syndrome have relied heavily on an improved understanding of mechanisms of disease. How does cancer cause weight loss, debility and anorexia A variety of different mediators have been described. Todorov et al. have discovered a 24-kilodalton proteoglycan derived from the MAC16 tumour line 9 and have labelled this mediator proteolysis-inducing factor (PIF). Although only a few studies have focused on PIF, antibodies to this substance appear to prevent weight loss in tumour-bearing animal models. Clinical data suggest that PIF is specific to cancer-associated wasting, as it is not found in cancer patients without weight loss nor in patients who are losing weight as a result of other diseases. To our knowledge, no clinical studies that have specifically focused on PIF inhibition have been reported thus far. In addition to this mediator, other mediators that appear to play an active role in cancer-associated anorexia weight...

Proinflammatory Cytokines and Anorexia

Another cause of CACS which, due to its particular aspects and appearance, may be considered specific for the syndrome is decreased food intake. Malnutrition may be considered a hallmark of cancer cachexia and it is associated with anorexia - that is, loss of appetite and or decreased food intake. Nutrition is a complex function resulting from the contribution of peripheral and central nervous afferents in the ventral hypothalamus. Stimulation of the medial hypothalamic nucleus inhibits feeding, while stimulation of the lateral nucleus promotes food intake. Among peripheral afferents, oral stimulation by pleasant tastes elicits eating, whereas gastric distension inhibits it. There is evidence that while the proinflammatory cytokines IL-1, IL-6, and TNF-a are involved in cancer-related anorexia and decreased food intake (see below), they are probably not the only mediators of CACS. Since multiple factors are involved in the control of food intake, it is possible that there are also...

Physical Activity and Anorexia

Clinical reports of anorexia nervosa have viewed excessive physical activity as an interesting but unimportant symptom of the syndrome. For example, Feighner et al. (1972) have described diagnostic criteria that include periods of overactivity as one of six possible secondary symptoms. In the traditional view, activity is secondary because it is simply a way that the anorectic burns off calories. That is, physical activity reflects the patient's desire to lose weight.

Antiserotonergic Therapies Targeting Anorexia and Cachexia

Disease-associated anorexia might be therapeuti-cally approached by interfering with the neuro-chemical events downstream of cytokine activation. Serotonergic hypothalamic neurotransmission represents a suitable example, and it is therefore tempting to speculate that by interfering with hypothalamic serotonin release, food intake might be improved. Hypothalamic serotonin synthesis strictly depends on the brain availability of its precursor, the amino acid tryptophan 10 . An increase of plasma and brain tryptophan levels, leading to increased brain serotonergic activity, has been demonstrated in different diseases and linked to the presence of anorexia and reduced food intake. Tryptophan crosses the blood-brain barrier via a specific transport mechanism shared with the other neutral amino acids, including the branched-chain amino acids (BCAA). Thus, by artificially increasing the plasma levels of the competing amino acids, a reduction of tryptophan brain entry could be achieved,...

Role of Brain Monoamines in Disease Associated Anorexia Cachexia

More data support a role for hypothalamic neurotransmission as an effective therapeutic target in the treatment of anorexia. Using in vivo microdial-ysis, Blaha et al. showed that intrahypothalamic serotonin concentrations are increased in anorec-tic tumour-bearing rats 22 . In the same study, they also showed a more complex derangement of hypothalamic monoaminergic neurotransmission, since dopamine levels were also found to be depressed 22 . This evidence may give the neurochemical explanation for the results obtained in anorectic cancer patients, whose food intake has been restored and quality of life improved by the administration of dopamine (L-DOPA) at a dosage ranging from 375 750 mg day 23, 24 . Although not obtained in prospective randomised clinical trials, these data are very intriguing and further support the 'monoaminergic' approach to the treatment of anorexia. The nitric oxide system and the production of eicosanoids might be of importance for the pathogenesis of...

On The Applied Side Activity Anorexia And The Interrelations Between Eating And Physical Activity

Twelve years later, Frank Epling (who was then an assistant professor of psychology at the University of Alberta) began to do collaborative research with David Pierce (author of this textbook), an assistant professor of sociology at the same university. They wondered if anorexic patients were hyperactive, like the animals in the self-starvation experiments. If they were, it might be possible to develop an animal model of anorexia. Clinical reports indicated that, indeed, many anorexic patients were excessively active. For this reason, Epling and Pierce began to investigate the relationship between wheel running and food intake (Epling & Pierce, 1988 Epling, Pierce, & Stefan, 1983 Pierce & Epling, 1991). The basic findings are that physical activity decreases food intake and that decreased food intake increases activity. Epling and Pierce call this feedback loop activity anorexia and argue that a similar cycle occurs in anorexic patients (see Epling & Pierce, 1992).

Treatment of Symptoms and Constipation as Causes for Secondary Anorexia Cachexia

In patients with advanced, progressive, incurable disease, the causes of anorexia, decreased oral intake and loss of weight are complex. Besides the primary (paraneoplastic) catabolic processes, a number of important causes for loss of appetite or weight may occur, such as severe symptoms (i.e. pain, shortness of breath, depression), syndromes (i.e. constipation, mucositis, bowel obstruction) or prolonged bed rest 12 . Poor assessment of interfering symptoms (see Chp. 9.11) by not acknowledging risk factors for symptom expression and insufficient symptom management (i.e. pain, depression, social distress), or negligence of the syndromes constipation 13 or sedation 14 can lead to sub-standard management.

Cytokines and Anorexia General

Several proinflammatory cytokines, including interleukin-1 (IL-1), IL-2, IL-6, IL-8, tumour necrosis factor-a (TNF-a) and interferon-y (IFN-Y), reduce food intake after peripheral or central administration in laboratory animals 3, 4 . Some cytokines suppress feeding synergistically 3, 4 . The anorectic effects of cytokines are pathophysi-ologically relevant because acute antagonism of particular cytokines and or their receptors often attenuates anorexia in various diseases or models of disease 5 . Furthermore, several immune challenges reduce food intake less in mice that are genetically deficient in a particular cytokine or cytokine receptor than in control animals (see below). Failure to establish a role for a particular cytokine in disease-related anorexia with genetic knock-out (KO) mice 5 is presumably due to the redundant and overlapping actions of cytokines, which allow for developmental compensation. Interestingly, the feeding-suppressive effect of proinflammatory cytokines...

Neuropeptides and Cancer Anorexia

Anorexia Food Groups

Food intake in tumour-bearing rats (TB-R) and control groups before and after tumour resection and sham operation, respectively. In the TB-R group, food intake decreased with the onset of anorexia. When rats were defined as anorectic, tumours were resected, while their controls underwent sham operation. Food intake continued to be measured until it normalised in TB-R, at which time rats in both groups were killed to harvest their brains. (From 59 ) Fig. 7. Food intake in tumour-bearing rats (TB-R) and control groups before and after tumour resection and sham operation, respectively. In the TB-R group, food intake decreased with the onset of anorexia. When rats were defined as anorectic, tumours were resected, while their controls underwent sham operation. Food intake continued to be measured until it normalised in TB-R, at which time rats in both groups were killed to harvest their brains. (From 59 ) ferent neuropeptides in cancer anorexia-cachexia syndrome, our knowledge...

Anorexia Nausea and Vomiting

Anorexia is common in patients on IFN, with loss of appetite and associated early satiety. Patients are frequently told to expect a 5-10 weight loss while on treatment with IFN. In overweight patients with hepatic steatosis, this weight loss can actually be beneficial, but some patients, particularly those with cirrhosis and catabolic malnutrition, do poorly with this degree of weight loss. Frequent small meals and use of high-calorie nutritional supplements are occasionally necessary. If patients lose more than 10 body wt, or have any associated symptoms suggestive of more serious disease, then a clinically appropriate workup for occult malignancy may be necessary.

Role of Brain Serotonin in Disease Associated Anorexia

Considering disease-associated anorexia as a pathological and persistent form of satiety, it is intuitive to speculate that the pathogenesis of anorexia could be related to a derangement of the physiological mechanism mediating satiety. As a consequence, much scientific effort has been devoted to clarify the involvement of hypothalam-ic appetite-suppressing circuits in the onset of anorexia. Many studies have been conducted in animal models of cancer anorexia, but it is reasonable to translate the results obtained to other diseases. Therefore, it appears that disease-associated anorexia is related to the inability of the hypothalamus to respond appropriately to consistent peripheral signals, primarily due to the hyperacti-vation of the melanocortin system. This derangement could be triggered by cytokines. The mechanisms by which cytokines negatively influence energy intake are currently under investigation. As proposed by Inui, cytokines may play a pivotal role in long-term inhibition...

Leptin and Cancer Anorexia Cachexia

The persistence of anorexia and the onset of cachexia in cancer patients, therefore, implies a failure of this adaptive feeding response 86 . Leptin, a member of the gp 130 family of cytokines, induces a strong T helper-1 lymphocyte response and is regarded as a proin-flammatory inducer 87 . Several data suggested a role of leptin in inflammatory diseases. Proinflammatory cytokines up-regulate leptin expression in white adipose tissue and increase plasma leptin levels in hamsters and mice 88 . However, in many common diseases associated with cachexia, such as chronic obstructive pulmonary disease and chronic inflammatory bowel disease, there is an inflammatory status caused by high proinflammatory cytokine levels, whereby leptin concentrations are decreased related to body fat mass. In patients with advanced non-small-cell lung cancer, serum leptin levels were lower than in controls and lower still in those who were cachectic who also showed an increase of...

Central Neural Mediation of Cytokine Induced Anorexia

The major hypothalamic detection site for blood-derived signals. Yet, severing the ARC from PVN or its connections with the PVN only slightly attenuated peripheral IL-1p-induced anorexia 35 , indicating that the ARC is involved but not necessary for peripheral IL-1p-induced anorexia. Several lines of evidence 20 implicate activation of hindbrain to forebrain aminergic neurons in the feeding suppression and hypermetabolic effects of circulating IL-1p. IL-1p-induced anorexia may in part be mediated through prostaglandin E2-dependent activation of serotoninergic neurons originating in the raphe nuclei and projecting to the hypothalamus 36 . In line with this idea, systemic administration of a serotonin (5-HT2c) receptor antagonist and microinjection of the 5-HT1A autoreceptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) directly into the raphe nucleus both markedly attenuated the feeding-suppressive effect of peripherally injected IL-1-p 3 . Interestingly, anorexia induced...

Leptin and Anorexia in Ageing

Ageing appears to be associated with leptin resistance. It has been found that the relatively hyper-leptinaemic state of ageing animals blunts the sensitivity of the hypothalamic energy regulatory system, thus decreasing appetite even during episodes of negative energy balance. It has been found that age-associated decreased levels of orexigenic signalling through AgRP and NPY neurons in the arcuate nucleus of the hypothalamus are accompanied by increased levels of anorexi-genic signalling through POMC CART neurons. This pattern of neuropeptide gene expression may contribute to the loss of appetite and anorexia associated with ageing 56 .

Anorexia and Bulimia

Eating disorders that make you underweight cause health problems as severe as those caused by overweight. Anorexia, or self-starvation, is rampant on college campuses. Estimates suggest that one in five college women, and one in 20 college men restrict their intake of Calories so severely that they are essentially starving themselves to death. Others allow themselves to eat, sometimes very large amounts of food (called binge eating), but prevent the nutrients from being turned into fat by purging themselves, often by vomiting. Binge eating followed by purging is called bulimia. Anorexia has serious long-term health consequences. Anorexia can starve heart muscles to the point that it develops altered rhythms. Blood flow is reduced and blood pressure drops so much that the little nourishment that is present cannot get to the cells. The lack of fat that accompanies anorexia can also lead to the cessation of menstruation, amenorrhea. Amenorrhea occurs when Health problems resulting from...

Anorexia Nervosa

Anorexia nervosa (AN) is characterised by a deliberate reduction of food intake in order to achieve an 'ideal' body weight and due to constant fear of getting fat. People affected by this disorder are constantly concerned with their body weight they try to reduce their body size and do not consider their weight loss as abnormal. AN patients have an altered way of experiencing their own body they 'feel they are fat,' even though they are underweight, and believe that some parts of their body are 'too fat,' even if they are objectively underweight. Table 1 lists the main criteria for the diagnosis of AN. Table 1. Diagnostic criteria for anorexia nervosa (DSM-IV)

Activity Anorexia

Substantial evidence indicates that excessive physical activity is central to an understanding of human self-starvation, or anorexia (Epling and Pierce, 1996a Pierce & Epling, 1991). Separate research areas indicate that, contrary to common sense, increasing amounts of physical exercise may reduce a person's appetite. Also, lowered food intake can induce physical activity. Thus, declining food intake produces activity and activity suppresses food intake. These two effects combine to produce an activity anorexia that occurs in animals and accounts for a significant number of cases of anorexia nervosa (Epling & Pierce, 1992).

Anorexia in Animals

The process of activity anorexia begins when rats are fed a single daily meal and are allowed to run on an activity wheel. It is important to note that the size of the meal is more than adequate for survival. Also, animals are not forced to exercise on the wheel. They can choose to remain in an attached cage or just lie in the wheel. In fact, the animals start running, and this activity increases daily because of the food restriction (Epling & Pierce, 1996b). FIG. 13.9. Excessive running and reduction of food intake by an adolescent rat reported in A Theory of Activity-Based Anorexia, by W. F. Epling, W. D. Pierce, and L. Stefan, 1983, International Journal of Eating Disorders, 3, 27-46.

Humans and Anorexia

The seemingly willful starvation of animals appears similar to cases of human anorexia. For humans, social reinforcement can increase the tendency to diet or exercise. An individual may learn these responses to escape or avoid criticism for being overweight or to gain approval for being slim and fit (see Pierce & Epling, 1997, for an analysis of the social contingencies). The type and intensity of dieting and exercise is initially regulated by the responses of others. However, once social reinforcement has encouraged food restriction, especially in the context of increasing exercise, the activity-anorexia cycle may be initiated. When the process starts, the person is trapped by the activity food reduction cycle. Humans self-impose diets for a variety of reasons. All diets do not generate excessive activity. The type, severity, and pattern of diet are important factors contributing to physical activity. For example, many anorexics change their meal pattern from several meals to one per...

Cancer Anorexia

Cancer anorexia is defined as the loss of the desire to eat, and several factors are involved in its pathogenesis. Anorexia and reduced food intake are physiological responses prompted by the growing tumour, and persistent anorexia compromises host defences, which ultimately delays recovery. Anorexia contributes to the development of malnutrition and cachexia, since it reduces the oral intake of calories, thus promoting skeletal-muscle wasting 13 . In the methylcholanthrene-induced sarcoma (MCA)-bearing Fischer rat, anorexia develops with progression of tumour growth, so that a characteristic feeding pattern is observed with the onset of anorexia (Fig. 1,11).A decrease in food intake occurs, first via a decrease in meal number associated with a simultaneous partial compensatory increase in meal size that lasts for approximately 24-48 h. Thereafter, meal size also decreases, and anorexia becomes apparent and profound 30-33 , leading ultimately to the rats' demise 32 . The decrease in...

Eating Disorders

Eating disorders, while not as common of a comorbidity in bipolar disorder as substance use or anxiety disorders, is overrepresented in bipolar disorder (Krishnan 2005). In an inpatient sample there was an association between bipolar illness and eating disorders and 32 of the patients had a history of suicide attempts and self-injurious behavior (Stein et al. 2004). While rates of suicides and suicide attempts is high in patients with eating disorders, there is not enough data currently available to know whether the presence of an eating disorder in patients with bipolar disorder increases the suicide risk compared with patients without eating disorders (Corcos et al. 2002).

Immunological Parameters of Nutrition

4.1 Anorexia 8.2 Treatment of AIDS Anorexia-Cachexia Syndrome and Lipodystrophy 9.9 Omega-3 Fatty Acids, Cancer Anorexia, and Hypothalamic Gene Expression Eduardo J.B. Ramos, Carolina G. Goncalves, Susumu Suzuki,Akio Inui, 10.4 Palliative Management of Anorexia Cachexia and Associated Symptoms 10.9 An Update on Therapeutics The Cancer Anorexia Weight Loss Syndrome in Advanced Cancer Patients Pharmaco-nutritional Support, Progestagen and Anti-COX-2 Showing Efficacy and Safety in Patients with Cancer-Related Anorexia-Cachexia and Oxidative Stress

Why Is My Husband So Angry

Elmer is illustrative of some of the far-reaching consequences that a partner's chronic pain problem can have on the health and well-being of the spouse. Prior to the onset of backache, Mr. Elmer was apparently an easygoing man, his marriage was satisfactory, and he was on the whole a caring partner and a father. Then this patient went through what can only be described as a dramatic personality change following the onset of his back problem. He withdrew almost entirely from all family activities, and periodically engaged in verbally abusive behavior, mainly toward his wife and occasionally toward the children. His wife became very fearful of these outburst and lived in fear of him. The family was confronted with serious financial problems. Mrs. Elmer had to contend with her fear of these outbursts especially when directed at the children. When seen at the pain clinic, she had the appearance of a person under great stress. She looked emaciated, and reported that she...

Consequences of Altered Glucose Metabolism Oxidative Stress

An inadequate detoxification due to altered glucose metabolism in addition to symptoms such as anorexia cachexia, nausea, and vomiting, that prevent a normal nutrition and thereby a normal supply of nutrients such as glucose, proteins and vitamins, leading to accumulation of ROS 53 . In a series of our recently published studies

Changes in Intermediary Metabolism During the Acute Phase Response

Low-density lipoproteins, decreased lipoprotein lipase activity, increased de novo triglyceride synthesis and esterification, increased release of free fatty acid from the periphery, and a futile cycle of fatty acids between the liver and adipose tissue beds. These changes, which are promoted by a variety of cytokines, maintain serum lipid concentrations despite the presence of anorexia 4 .

Nucleoside Reverse Transcriptase Inhibitors

Adverse reactions early in treatment may include anorexia, nausea, vomiting, headache, dizziness, malaise and myalgia, but tolerance develops to these and usually the dose need not be altered. More serious Eire anaemia and neutropenia which develop more commonly when the dose is high, and with advanced disease. A toxic myopathy (not easily distinguishable from HIV-associated myopathy) may develop with long-term use. Rarely, a syndrome of hepatic necrosis with lactic acidosis may occur with zidovudine (and with other reverse transcriptase inhibitors).

General Symptom Data on Children at the End of Life

A retrospective chart review examined the signs and symptoms occurring at the end of life in 28 children dying from cancer in Japan. All children experienced anorexia, 82.1 had dyspnea, and 75 had pain. Other symptoms included fatigue (71.4 ), nausea vomiting (57.1 ), constipation (46.4 ), and diarrhea (21.4 ) (4). This symptom profile parallels that of the North American reviews of the symptoms of dying children (2,5,6).

Neurophysiology Responses

The behavioural mode of action of cytokines has been found to be consistent with the neurophysio-logical pattern induced by a cytokine 11, 27 . For instance, IL-1p activates specifically and reversibly the glucosensitive neurons in the ventromedial hypothalamic nucleus or VMN (a site involved in the integrative control of meal termination). This would predict changes of meal size and meal duration as those induced by IL-1p. Based on the data of IL-1p-induced inhibition of the inward calcium channel current (and hence calcium permeability), a model has been proposed that would be consistent with an IL-1p long-lasting VMN neuronal activity modulation that may be associated with the long-term anorexia induced by the cytokine. A decrease of calcium influx in VMN glucose-sensitive neurons may inhibit the defined calcium-dependent potassium conductance in these neurons, leading to maintenance of intracellular potassium, depolarisation and increase in neuronal activity.

General Symptom Data in the Context of Life Limiting Illness

The pattern of symptoms based on the self-report of US children aged 10-18 years treated for cancer was studied (7). This study included children across the spectrum of illness and included newly diagnosed patients, those receiving a bone marrow transplant, and those receiving palliative care. It showed that children with cancer are very symptomatic and are often highly distressed by their symptoms. A prevalence rate greater than 35 was noted for the symptoms of pain, drowsiness, nausea, cough, anorexia, lack of energy, and psychological upset. Inpatients reported being more symptomatic than their outpatient cohort, as evidenced by comparing their mean number of symptoms of 12.7 4.9 and 6.5 5.7, respectively. Recent administration of chemotherapy is associated with significant symptomatology in children with cancer (7). Children with solid tumors were more symptomatic than children with other malignancies. Pain, nausea, and anorexia were clustered as highly distressing symptoms (7)....

Transducing Mechanisms and Functional Antagonism

And is indirect since IL-1 receptors are not G-pro-tein coupled. Receptors coupled to GaO that respond to feeding-stimulatory signals include receptors for galanin, endogenous opioids, and neuropeptide Y. Thus, IL-1p-induced modulation of GaO protein may be involved in IL-1p-induced brain activities and anorexia including antagonism of neuropeptide Y action. The consequence of this cytokine mode of action is broad. G-protein-coupled receptors that have been associated with energy balance regulation by the brain include receptors for cate-cholamines, serotonin, histamine, neuropeptide Y, hypocretins orexins, melanin-concentrating hormone, agouti-related protein, a-melanocyte stimulating hormone, IL-8 and other chemokines intercrines, cholecystokinin, opioids, glucagon and others. Cytokines have the ability to modulate mechanisms associated with all of these endogenous substances, and therefore, the potential of cytokine-induced modulation of G-proteins - the interface between...

Ten Aspects To Consider for Future Research into Brain Mechanisms Involved in Wasting and Cachexia

Links and feedbacks exist among neurological, psychological and psychiatric manifestations of diseases accompanied by wasting and cachexia. Symptoms or signs such as anxiety, depression, cognitive impairment, fatigue and asthenia, and anorexia can exacerbate wasting and cachexia due to deleterious positive feedback cycles. This increases the frequency of complications, decreases the quality of life and activities of daily living and performance, and has an impact on overall morbidity and mortality. What are the main mechanistic interactions and magnitude of the individual contributions responsible for symptomatology interface

Thyroid Disorders Thyrotoxicosis

Anorexia occasional, usually younger patient with mild disease, weight gain may occur when caloric intake exceeds metabolic demand 18 . Anorexia, rather than hyperphagia, occurs in about one-third of elderly TS patients and contributes to the picture of apathetic TS 22 .

Adrenal Insufficiency and Weight Loss

Primary adrenal insufficiency can develop as acute adrenal insufficiency or adrenal crisis, in which shock and gastrointestinal symptoms are prominent, or as a slow process characterised by weight loss (commonly associated with nausea, vomiting, and anorexia), hyperpigmentation of the skin and mucosae, and electrolyte disturbances. Thus, nausea, vomiting, and a history of weight loss and anorexia, coupled with dehydration and hypotension represent some of the clinical features suggesting adrenal insufficiency 25,27 . Anorexia

Ectopic ACTH Syndrome and Weight Loss

Most patients affected by ectopic ACTH syndrome have malignant tumours, half of them being small-cell lung carcinoma. The metabolic manifestations appear suddenly and progress rapidly while the typical Cushing's habitus is absent. Anorexia, weight loss, and anaemia are frequent and comprise the picture of neoplastic cachexia 30,31 .

Use in Prevention and Therapy

During increased physiologic stress, body requirements for BCAAs are greatly increased relative to other amino acids. Supplemental BCAAs are important in conserving body stores of protein in chronic illness, anorexia nervosa, very low-calorie diets, injury, surgery, burns, or infection.3 Anorexia. Appetite and food intake are increased when serotonin levels in the brain are low. By reducing brain uptake of tryptophan (the precursor of serotonin), BCAAs may increase appetite and food intake in disorders where appetite is lost (chronic infection, AIDS, cancer).

Hypothalamic Diseases and Weight Loss

Besides pituitary dysfunction, diseases of the hypothalamus can cause abnormal mental function and behavioural disorders, including hyper-phagia which leads to marked obesity or anorexia with weight loss 36 . Indeed, the hypothalamus is involved in the regulation of diverse functions and behaviours -in particular, social behaviours, sleep, sexuality, body temperature, and eating patterns. The abnormal eating pattern in subjects affected by hypothalamic lesions include exaggerated and uncontrolled food intake (binge eating, or bulimia) or profound anorexia with cachexia, as in Simmond's disease 37 . These are analogous to syndromes of hyperphagia produced in rats by destruction of the ventromedial nucleus or of connections to the paraventricular nucleus, while lateral hypothalamic damage causes profound anorexia 36 .

Role of Hypothalamic Neuroimmune Interactions

Recent data suggested that hypothalamic sero-tonergic neurotransmission may be critical in linking cytokines and the melanocortin system. Fenfluramine is a serotonin agonist once widely prescribed in the treatment of obesity. It has been recently shown that fenfluramine raises hypothal-amic serotonin levels, which in turn activate POMC CART neurons in the arcuate nucleus, therefore inducing anorexia and reduced food intake 54 . It is also well-documented that cytokines, and particularly IL-1, stimulate the release of hypothalamic serotonin 55 . Thus, it could be speculated that during disease cytokines increase hypothalamic serotonergic activity, which in turn contributes to persistent activation of POMC CART neurons, leading to the onset of anorexia and reduced food intake. Supporting the role of serotonin in the pathogenesis of anorexia, we demonstrated that in anorectic tumour-bearing animals hypothalamic serotonin levels are increased when compared with the levels in control rats...

Nutritional Support

In case of hypona-traemia, water restriction should be imposed, and in case of ascites or oedema, sodium restriction is needed. Cirrhosis patients with encephalopathy require protein restriction and solutions enriched in branched-chain amino acids (BCAAs) 78 . Because BCAAs compete with tryptophan, which is the precursor of brain serotonin, across the blood-brain barrier, they block the increased hypothalam-ic activity of serotonin that strongly decreases appetite therefore, BCAAs may also serve to counteract anorexia and cachexia 79 .

Other Indications For Antidepressants

SSRIs are effective in milder cases of the eating disorder bulimia nervosa, particularly fluoxetine (in higher doses than are required for depression). This effect is independent of that on depression (which may co-exist) and may therefore involve action on transmitter systems other than those involved in modulating depression. Antidepressants appear to be ineffective in anorexia nervosa.

Cachexia Pathophysiology

Cachexia in the elderly cannot be completely explained by reduced food intake rather, several social and psychological factors, disease conditions, and medications can aggravate the physiological anorexia of aging and lead to weight loss 1 . Furthermore, a person eats less when he or she eats alone compared to when eating in a group. The pleasurable qualities of food are determined by taste, smell, and vision 1 , with olfaction being the most important determinant 1 . The decreased sense of smell and the changes in taste that occur with aging (taste threshold, difficulty in recognising taste mixtures, and increased perception of irritating tastes) contribute to anorexia 1 . Other factors that contribute to the development of cachexia are detailed in the following sections.

Tumour Necrosis Factor

Depend on the site of production 40 . This was demonstrated by intracerebral injection of TNF-a-secreting cells, which resulted in body weight loss and anorexia, while TNF-a-producing cells inoculated into peripheral tissue triggered cachexia, including weight loss, depletion of lipid and protein stores, and anaemia but without significant anorexia 39,40 .

Symptoms and Complications

The incubation period is approx 6 weeks to 6 months. As the name suggests, the virus primarily affects the liver. Typical symptoms include malaise, anorexia, nausea, mild fever, and abdominal discomfort and may last from 2 days to 3 weeks before the insidious onset of jaundice. Joint pain and skin rashes may also occur as a result of immune complex formation. Infections in the newborn are usually asymptomatic.

Medroxyprogesterone Acetate and Megestrol Acetate Clinical Experiences

Medroxyprogesterone Acetate In two clinical studies 22, 66 , we used MPA(1 g day, os) and a hypercaloric diet to correct anorexia and cachexia occurring in HIV-infected patients. In the first study 22 , MAP was administered to 74 AIDS patients. The control group of 96 The progestogenic synthesised derivative MA has been successfully used in the treatment of neoplas-tic cachexia, anorexia, and in AIDS patients 24,56, 81-83 , but the optimal dosage of the drug remains to be defined. Also, the mechanism of action of MA is many-sided and not yet completely understood. It is thought that the stimulation of appetite by progestogens takes place at the hypo-thalamic level 84-86 . A second effect of MA, which has been demonstrated in vitro, is the promotion of fibroblast transformation into adipocyte. Finally, evidence has emerged showing anti-TNF and anti-IL-1 action 83 . may be achieved with a dose of 320 mg day. We designed a controlled study to evaluate the safety and efficacy of MA at...

Regulation of Appetite in the Elderly

Adaptive Relaxation Stomach

Regulation of appetite is a sophisticated process that involves feedback from peripheral sensory endings and the interaction of a variety of neurotransmitters in the central nervous system 1 . Numerous studies have shown that food intake declines over the human lifespan, with males having a greater decrease in food intake than females. A large part of the anorexia of aging seems to be related to the changes in gastrointestinal activity that occurs with aging 1 . Starvation (Anorexia of aging) The hormone leptin is released from adipose tissue 18 and exerts its effects by decreasing food intake and increasing the metabolic rate. Circulating leptin levels increase in older men and decrease in older women 19 . The increase in lep-tin levels in men is related to the decrease in testosterone that occurs with aging 1 , which, in turn, is associated with muscle loss 20 and an increase in body fat 21 . Testosterone replacement in older men leads to a decline in leptin levels 1 . The increase...

Factors Other Than Cytokines

In addition to humoural factors, tumour-derived molecules have also been suggested as mediators of cancer cachexia. Firstly, cancer cells are capable of constitutively producing cytokines. These may act on cancer cells in an autocrine manner or on supporting tissues, such as fibroblasts and blood vessels, to produce an environment conducive to cancer growth 31 . While tumour-produced cytokines may have a more important role in the anorexia-cachexia syndrome, several compounds produced by the host 32 are likely to have an important role in mimicking the metabolic

Alternative Models of Cachexia

Most of the studies that have identified cytokines as important determinants in cancer cachexia have employed rat tumours. These tumours tend to grow rapidly, have a strong anorectic component, and may require large tumour masses before cachexia is apparent. However, most human tumours grow slowly, can produce cachexia in the absence of anorexia 5 , and the tumour mass does not normally exceed 5 of the body weight. In human cachexia, there is also evidence for a circulatory factor capable of inducing protein degradation in skeletal muscle in patients with weight loss 10 6 . MAC16 is a chemically induced, transplantable adenocarcinoma of the colon, that is passaged in inbred NMRI mice 7 .In male animals,weight loss occurs when the tumour mass comprises more than 0.3 of body weight and reaches 30 when the tumour represents just 3 of body weight 8 . Weight loss involves a decrease in both carcass fat and skeletal muscle mass and is directly proportional to the weight of the tumour....

Role of Ghrelin in Cachexia

The infusion of ghrelin stimulates eating and produces obesity in rats 79 , and a study in humans showed that ghrelin infusion led to short-term increase in hunger 80 . Maintenance of weight reduction after gastric bypass surgery was suggested to be due to markedly low levels of ghre-lin 76 . It has also been shown that ghrelin levels are elevated in cachectic patients with chronic heart failure or anorexia nervosa 78 . Several studies are currently underway to explore the effects of ghrelin and its agonists on cachexia.

Strategies To Fight Cachexia Based on Cytokines and Transcriptional Factors

Since both anorexia and metabolic disturbances are involved in cancer cachexia, the development of different therapeutic strategies has focused on these two factors. Unfortunately, counteracting anorexia either pharmacologically or nutritionally has led to rather disappointing results in the treatment of cancer cachexia. It is basically for this reason that the strategies mentioned below rely on neutralising the metabolic changes induced by the tumour, which are ultimately responsible for the weight loss. Therefore, taking into account the involvement of cytokines in cachexia, therapeutic strategies have been aimed at blocking either their synthesis or their action.

Structure Of Biguanides

Sar Sulfonylurea

2.3.1.1 Side Effects, Adverse Effects. The major side effects associated with metformin therapy are gastrointestinal, including diarrhea, nausea, abdominal discomfort, and anorexia, which improve with dose reduction and can be minimized by slow dose titration (3, 118). Lactic acidosis, a serious often fatal side effect associated with biguanides, is rare

Anionexchange resins bile acid sequestrants

About half the patients who take Colestyramine experience constipation and some complain of anorexia, abdominal fullness and occasionally of diarrhoea these effects are dose-related but may limit or prevent its use. Because the drug binds anions, drugs such as warfarin, digoxin, thiazide diuretics, phenobarbitone and thyroid hormones should be taken 1 h before or 4 h after Colestyramine to avoid impairment of their absorption.

Nutrition in the Palliative Care Context

The goal of palliation is to alleviate the suffering of patients and their relatives that is caused by distressing symptoms and complications. Treatment is based on active assessments that take into account multidimensional (physical, psychological emotional, social, spiritual existential) aspects 6 . Palliative nutrition aims to primarily improve subjective well-being of patients and their relatives, rather than to improve weight or nutritional intake per se (for further discussion of this concept, see the chapter 'Palliative Management of Anorexia Cachexia and Associated Symptoms').

Symptom Assessment Close to the Patients Endof Life Multidimensional Issues

Eating-related symptoms may also carry a more multidimensional meaning, one that reflects the suffering. The concept of 'total anorexia' has not been defined, although attempts have been made to define 'total pain.' Likewise, a staging system for eating-related symptoms, in order to identify refractory eating-related symptoms, has not yet been developed.

Assessment Instruments for Eating Related Distress

Traditional instruments, such as the FAACT (Functional Assessment of Anorexia Cachexia Therapy) for anorexia cachexia, or widely used quality-of-life instruments, such as the EORTC-QlQ-c30, carry some items related to distress, but they were not specifically developed for the purpose of assessing distress. The FAACT 19 , as an example, asks at least three distress-related questions 'I am worried about my weight' (item 3), 'I am concerned how thin I look' (item 5), and 'my family or friends are pressuring me to eat' (item 8). In the general section of the FACT, there is a question regarding the impact of physical function on social contacts (item 3). In the EORTC-QlQ-c30, questions assessing interference with (physical) function (items 6, 7) or social contacts (items 26, 27) may depict issues related to cachexia and weakness, but not directly to eating. As a solitary symptom, only the impact of pain on daily life (item 19) is included in the EORTC-QLQ-C30, but there are no items...

Specific Diagnostic Criteria

The focus of the anxiety and worry is not confined to features of an Axis I disorder, e.g., the anxiety or worry is not about having a Panic Attack (as in Panic Disorder), being embarrassed in public (as in Social Phobia), being contaminated (as in Obsessive-Compulsive Disorder), being away from home or close relatives (as in Separation Anxiety Disorder), gaining weight (as in Anorexia Nervosa), having multiple physical complaints (as in Somatization Disorder), or having a serious illness (as in Hypochondriasis), and the anxiety and worry do not occur exclusively during Posttraumatic Stress Disorder.

Reviewing Client Problems

Similarly, the lay public overuses the terms compulsive and panic. In diagnostic circles, compulsive behavior generally alerts the clinician to symptoms associated with either obsessive-compulsive disorder or obsessive-compulsive personality disorder. In contrast, many individuals with eating disorders and substance abuse disorders refer to their behaviors as compulsive. Once again, further questioning is needed before assuming that the client is suffering from a compulsive disorder. Finally, panic disorder is a very specific syndrome in DSM-IV-TR. However, many individuals with social phobias, agoraphobia, or public speaking anxiety talk about being frozen with panic. Therefore, although client use of the word panic should alert the interviewer to the possibility of an anxiety disorder, the appropriate diagnosis may not be panic disorder.

Decreased Food Intake

Malnutrition may be considered one hallmark of cancer cachexia and it is associated with anorexia, that is, loss of appetite and or decreased food intake. Appetite is a complex function resulting from the contribution of peripheral and central nervous afferents in the ventral hypothalamus. Stimulation of the medial hypothalamic nucleus inhibits feeding, while stimulation of the lateral nucleus promotes food intake. Among peripheral afferents, oral stimulation by pleasant tastes elicits There is evidence that proinflammatory cytokines such as IL-1, IL-6 and TNF-a are involved in cancer-related anorexia and decreased food intake, but these cytokines do not seem to be the only mediators of CAC. Since multiple factors are involved in the control of food intake, it is possible that there are also many factors contributing to the tumour-associated anorexia. Indeed, anorexigenic compounds are either released by the tumour into the circulation or the tumour itself may induce metabolic changes...

Signs and Symptoms of the Arteritic Form of AION j Note

Giant Cell Arteritis

The average age at the onset of anterior ischemic optic neuropathy in patients with temporal arteritis (AAION) is about 75 years. Arteritis can also present with branch retinal vessel occlusions, choroidal infarctions, or retinal ischemia, as indicated by the presence of numerous cottonwool spots. Ischemic pareses of the extraocular muscles may be present, and ischemia of the scalp, sufficient to cause patchy areas of hair loss, have been known to appear. Even myocardial infarctions, hemispheric strokes, and cranial nerve palsies can be caused by severe forms of arteritic disease. Temporal arteritis (also called giant cell arteritis, cranial arteritis, or Horton's cephalgia a now-obsolete term ) has the following typical signs and symptoms headache, jaw claudication, scalp pain when combing or brushing the hair, malaise, fatigue, low-grade fever, anorexia, migratory myalgias, weight loss, and thickened, cord-like enlargements of the superficial, subcutaneous arteries of the scalp (...

Social Causes of Weight Loss

Hospitalised AIDS patients, who take in only 70 of resting energy expenditure (REE) needs and 65 of protein needs, excluding the extra needs resulting from the hypermetabolism associated with fever, acute infections, and physical activity. Dietetic deficits in protein and calorie consumption interfere with the natural course of the main disease, emphasising subjective symptoms such as sickness, asthenia, anorexia, emesis, and constipation, which in turn interfere with feeding. A close relationship exists between susceptibility to infectious diseases and nutritional status regular nutrition and general good health make individuals more resistant to infections. Similarly, anergy to cutaneous tests (PPD, candidin, DNCB, etc.) is closely related to body-weight insufficiency and hypoalbuminaemia. The pre-surgical correction of denutrition reduces the incidence of post-surgical infectious complications, favouring the healing of the wounds and a quicker return to health 18-20 .

Cytokines General Comments

Multiple classes of cytokines have been proposed to participate in the induction and development of wasting and cachexia including via brain mechanisms. These comprise IL-1, IL-6 subfamily members including CNTF and leukaemia inhibitory factor, IFN-y, TNF-a and BDNF, which in many cases also induce anorexia 9,11,14, 28 . Studies have shown that intratumoral administration of IL-1 receptor antagonist significantly

Possible Complications

Even when appropriate caloric intake is offered, problems may exist with absorption and metabolism.15 Furthermore, eating disorders in infants and toddlers may be observed following long-term, intensive medical care. Extracardiac factors such as disturbed parent-child interaction may enhance disturbances of growth.16 Early definitive correction of cardiac defects provides optimum conditions for successful catch-up growth and a normalization of the physical development.15 Another recently recognized, and frequently underdiagnosed problem relates to young teenagers, usually female, who present with eating disturbances associated with a disturbed body image.

Nonsteroidal Anti Inflammatory Drugs

Inhibiting PG production by the rate-limiting enzymes known as cyclo-oxygenases (COX). Because traditional NSAIDs inhibit both COX-1 and COX-2, these drugs induce adverse effects such as gastrointestinal injury up to ulceration, reduced appetite and consequent reduced body weight indeed, these drugs may be considered a potential cause of anorexia in patients with cancer.

Consequences for the Family

Interventions) in connection with hospitalization and frequent outpatient visits, and the overall worries about the child, impose grave stress on parents, siblings, and the entire family environment. Oftentimes, long-lasting separation of family members related to attending to the child in hospital, as well as emotional stress caused by the severe and often life-threatening heart defect of the child, also evoke psychological and somatic consequences and conflicts within the family.26 Siblings suffer from lack of attention, often feel neglected, over-challenged, and misunderstood, and thus develop emotional disorders on their part. These may be eating disorders, sleeping disorders, regressive behavioral disorders, aggression, and or problems in academic performance. It is crucial to approach such psychological burdens immediately and to counteract or solve conflict situations. At this point, the help of professionals (psychologists, social education workers, and social workers) who...

Proinflammatory Cytokines

Solid tumours 15 , this cytokine has been implicated as the initiating signal for a variety of cellular and metabolic events seen in critically ill patients. TNF-a may circulate predominantly as a complex with its soluble receptors, making detection of the bioactive ligand more difficult. Increased levels of these soluble TNF-a receptors are seen in response to diverse inflammatory stimuli including sepsis, cancer and AIDS 16 . Nevertheless, elevated TNF-a levels are detected in many disease states including bacterial infections, cancer, sepsis and AIDS 17 . TNF-a is a metabolic hormone acting both in a paracrine fashion, and, in some istances, as an endocrine hormone 18 . Systemically, TNF-a has been suggested to act in the brain to cause anorexia and subsequent body weight loss 19 . The metabolic effects of TNF-a seem to promote redistribution of body protein and lipid stores. The result is a net loss of peripheral tissue protein with a concomitant increase in hepatic uptake 20 ....

The Gastrointestinal Tract

Pain Intestine And Bladder Fistula

How is your appetite is a good starting question and may lead into other important areas such as indigestion, nausea, vomiting, and anorexia. Patients often complain of indigestion, a common complaint that refers to distress associated with eating, but patients use the term for many different symptoms. Find out just what your patient means. Possibilities include Anorexia, nausea, vomiting in many gastrointestinal disorders also in pregnancy, diabetic ketoacidosis, adrenal insufficiency, hypercalcemia, uremia, liver disease, emotional states, adverse drug reactions, and other conditions. Induced but without nausea in anorexia bulimia. Anorexia is a loss or lack of appetite. Find out if it arises from intolerance to certain foods or reluctance to eat due to anticipated discomfort. Nausea, often described as feeling sick to my stomach, may progress to retching or vomiting. Retching describes the spasmodic movements of the chest and diaphragm that precede and culminate in vomiting, the...

Palliative Nutritional Endpoints and Decision Making

A careful multidimensional evaluation is the basis for treatment decisions for patients with advanced illness, such as cancer, suffering from anorexia, cachexia and related symptoms (see also Chp. 9.11 'Eating-related Distress of Patients with Advanced, Incurable Cancer and Their Partners'). In order to prioritise anorexia cachexia in the present (and often rapidly fluctuating) context, the patient should be assessed considering concurring physical (anorexia, fatigue, asthenia, body image, chronic nausea), psychological-emotional (anxiety, worthlessness, anhedonia), social (meal-ritual, express love through cooking) and spiritual-existential (bread of life) symptoms and distress. The subsequently developed comprehensive management approach involves team interactions and agreement with the patient and family about treatment goals and meaningful outcomes. The goals of the intervention may concentrate predominantly on changes in body image, focus on improvement of function, consist in...

Palliative Symptom and Syndrome Management

For palliative treatment of anorexia, the progestins are still the most effective drugs, but with limited effects on other nutritional endpoints. It remains to be discussed with the patient, whether the pure improvement of the sensation of appetite is a meaningful endpoint considering the side-effects and price. Corticosteroids are effective, but only for a few weeks, then side-effects gain importance. Prokinetics are helpful for chronic nausea in a subgroup of patients. Newer treatments have the Constipation often causes symptoms such as anorexia, early satiety or nausea before it is perceived as a symptom (feeling of incomplete evacuation, fullness of the bowel, etc.). It needs to be diagnosed as a syndrome (history, X-ray abdomen, rectal examination), not as a symptom.

The Diagnosis of Cancer Cachexia and its Implications

However, not all patients will conform to the stereotypical image of 'cachexia' for example, they may still be technically overweight despite having lost a substantial mass of lean tissue or they may be relatively weight-stable despite significant physiological change.

Nutritional Therapy Background

Patients with advanced cancer may have an inadequate nutritional intake and fail to increase appropriately their intake in response to increased resting energy demands 18 . Intake may be reduced by 'primary' mechanisms induced by the cachexia syndrome (and manifesting as anorexia or early satiety) or may be 'secondary' to problems such as mechanical gut obstruction or impaired swallowing, nausea, constipation, depression, gastrointestinal fungal infection and treatment side-effects (e.g. opiates, antibiotics, chemotherapy, radiotherapy). Such secondary problems should be proac-tively sought and appropriately managed. In addition, the medical team should also be alert to the risk of deteriorating nutritional status when patients are hospitalised 19,20 . The pathogenesis of 'primary' anorexia early satiety and the control of human appetite are incompletely understood. At the present time,

Conventional Nutritional Support

The broad aims of nutritional support for cachectic cancer patients are to improve function and well-being, to reduce morbidity and mortality and to strengthen patients for further challenges that may be imposed upon them. A number of trials have studied conventional nutritional support in cancer patients, several in patients receiving anti-tumour therapy. These therapies may themselves be regarded as 'stressors' that can continue for weeks or months. Furthermore, many cancer interventions may exacerbate reductions in energy and nutrient intake. Surgical patients may be fasted for prolonged periods perioperatively and both chemotherapy and radiotherapy may induce side-effects such as anorexia, nausea, vomiting, mucosi-tis, taste change or lethargy (depending of course on the drugs being used and the location, treatment volume and dose of radiotherapy) 27 . Current understanding as to how nutrition and chemotherapy interact is incomplete 28-30 . Intuitively a nutritionally replete...

Refining Oral Nutritional Support

For any oral nutritional supplement to be effective it must be consumed and unfortunately patients with advanced cancer frequently demonstrate anorexia, early satiety and alteration in taste and food preference. These obstacles to increasing oral nutritional intake suggest that appetite and desire for food will often need to be improved if an oral

Approach To Hyperthyroidism Definitions

Metabolism Weight loss is a common finding, especially in older patients who develop anorexia. However, sometimes, especially in young adults, weight gain can occur as a consequence of markedly increased caloric intake. Many patients develop an aversion to heat and a preference for cold temperatures.

Endocrine Abnormalities and Cytokines

Colony Abbreviations

The clinical symptoms of anorexia, nausea, fever, asthenia, fatigue, lethargy, myalgia, sickness, diarrhoea, anaemia, leucocytopaenia, tachycardia, headache, neurovegetative disturbances, etc., can be attributed to the release of cytokines by macrophages and activated inflammatory cells. Lipid metabolism disturbances, anorexia, and weight loss together lead to cachexia and are caused by the combined action of TNF, IL-1, IL-6, and IFN-y, the production of each being stimulated by infections and cancer 82, 83 . We demonstrated 84 high levels of TNF-a in HIV patients who had lost more than 10 of their ideal weight (Table 3).

Cachexia Cachexia Therapy and Protein Nutrition

A large fraction of patients with advanced cancer develop cachexia 1 , a wasting syndrome characterised by anorexia, asthenia, and profound losses of adipose tissue and skeletal muscle mass. The association of cachexia syndrome with poor prognosis, loss of functional status and poor quality of life has motivated researchers to develop therapeutic strategies for this problem 2 .

First Clinical Study Of Immune Gene Therapy For Patients With

The intravenous infusion of transduced cells was well tolerated. None of the patients experienced immediate toxicity or adverse events. The patients in groups 1, 2, and 3 commonly experienced flu-like symptoms. These included fever, fatigue, and anorexia, which began within

Second Order Neuronal Signalling

The hypothalamic arcuate nucleus, where peripheral signals mainly converge, projects to other hypothalamic areas, thus interacting with a number of neuronal populations 20 . Many pathways serving as second-order neuronal signalling pathways, including those of orexins A and B, have been described but their involvement in the pathogenesis of anorexia has so far received little attention, although it cannot be excluded. In a recent study, Li et al. showed that a loss of renal function in Wistar rats reduced hypothalamic orexin A, a prophagic mediator 33 , which in turn may have contributed to the development of anorexia in these animals. Evidence exists suggesting that disease-associated metabolic changes, and particularly alterations of protein turnover, impact on the neu-rochemistry in localised brain areas 34 . However, they also appear to have a role in sustaining and corroborating anorexia, while its onset seems to be secondary to the inability of the hypothalamus to recognise and...

Other Antiinflammatory Agents

One of the most promising studies to look at anti-inflammatory agents was a landmark trial from Lundholm et al. 27 . In a placebo-controlled trial, these investigators found that indomethacin resulted in an improvement in survival in advanced cancer patients with the anorexia weight loss syndrome. Since then, other studies have suggested that non-steroidal anti-inflammatory agents may play a role in treating this syndrome 28 . Although direct antineoplastic effects may be at work in achieving these benefits, the implication that the cancer anorexia weight loss syndrome is mediated by inflammation suggests that these agents might also be directly treating this syndrome. Further confirmatory clinical studies and further mechanistic studies with these agents in this setting are indicated.

Mechanism of Action of High Dose Progestins in CACS

The first question has been answered in a trial on a group of 65 patients with non-hormone-sensitive tumours, undergoing treatment with 2000 mg day of MPA (Fig. 1, bottom) appetite (anorexia) improved in 62 of patients, while body weight increased significantly (more than 0.5 kg) in 63 4 .

Controlled Trials on MPA

Placebo-controlled trials 9-13 on the effect of MPA treatment on anorexia and body weight generally confirmed an improvement in both parameters (Table 2). It is important to remark that in three studies 9-11 MPA was administered during chemotherapy, and that in the same studies an improvement in quality of life was reported. Nevertheless, in contrast with our previous experience, those authors 13 who analysed body composition demonstrated that the bulk of the weight gain was due to increased body fat, while fat-free mass was not significantly influenced by the treatment. Anorexia

Outcomes of a Palliative Treatment of Cancer Cachexia

Moreover, the main outcomes and the surrogate outcomes of a medical approach should be defined in clinical research, and the relationship between main and surrogate outcomes represents an open question not yet fully answered 74-79 . Indeed, there are no definitive data distinguishing main and surrogate end-points in quality-of-life assessment, and the relationship between symptom control and quality of life in an outcome analysis is still unclear. Symptom assessment surely represents the core of the validated instruments for quality-of-life assessment, but it cannot represent by itself a validated instrument for quality-of-life assessment. It follows that symptom assessment can be an index of activity of a treatment, or a surrogate end-point of quality of life, but quality of life must be considered either the main outcome of a treatment in palliative care, or the main index of efficacy of the treatment 74 . If we assume that symptom assessment represents an index of activity, and...

Corticosteroids or High Doses of Progestagens The Best Choice in Clinical Practice

In the previous paragraphs we have reviewed the evidence supporting the use of corticosteroids or progestagens in the treatment of cancer anorexia-cachexia, supplying either the evidence of activity and efficacy (if any), or the limits of their use in clinical practice. The next step is the evidence-based analysis of the reasons for selecting one approach rather than another in clinical practice. Most reviews suggest some assumptions that are worthy of critical analysis

Objectives for a Clinical Trial

There is concordance of opinion amongst physicians, clinical scientists and regulatory health authorities on the value of multicentre, randomised, controlled clinical trials, with adequate statistical power and preferably double-blinded, to determine the true effects of an intervention with therapeutic intent. To evaluate treatment of a complex syndrome such as cachexia, rather than a distinct or singular abnormality, those design features may be considered requisite. Restrictive protocol eligibility criteria and stratification on prognostic factors must be used to limit the impact of various co-morbidities, concomitant medications, patient histories and physicians' treatment patterns and skills. Patients with eating disorders, infections, maldigestion, malabsorption or diarrhoea, adrenal or thyroid diseases should be excluded. Efforts to limit disparities among the patients may reduce confounding variables but also will limit the validity of generalisations about the results from the...

Branched Chain Amino Acids

Other attempts at improving anorexia with nutritional substrates such as branched-chain amino acids (BCAA), which have been used in TPN, are still under investigation. BCAA can compete with tryptophan (the precursor of serotonin in the central nervous system, thus reducing serotonin production and increasing food intake 136 . Tayek et al. found that BCAA-enriched formulas improved albumin synthesis and may favourably influence protein metabolism in cancer cachexia 137 . Once again, the efficacy of BCAA in the geriatric setting is unknown.

N3 Fatty Acids and Fish

N-3 fatty acids, mainly from fish oils, interfere with the cyclooxygenase (PGE2 production) and lipooxygenase metabolic pathways. They also inhibit cytokine synthesis and activity 151, 152 . Dinarello 153 and Endres 154 found that N-3 fatty acids improved food intake in rats with IL-1-induced anorexia. Tisdale and Dhesi also reported that using omega-3 fatty acids stopped the weight loss in an experimental cachexia model 155 . While the role of N-3 fatty acids in the treatment of cancer cachexia remains unclear 156 , their potential role in the treatment of cancer cachexia is promising 157,158 .

Family Therapy Outcome

The literature on the merit of family therapy for health problems include studies on stroke (Clark et al., 2003), cancer (Keller and Jost, 2003 Sellers, 2000), diabetes (Hagglund et al., 1996 Satin et al., 1989), anorexia nervosa (Ball, 1999), and depression (Chase and Holmes, 1990 Clarkin et al., 1990 Lebow and Gurman, 1995 Stevenson, 1993 Waring et al., 1995). A comprehensive literature search failed to produce any controlled outcome study for family therapy and chronic pain disorders. However, there is one study that investigated the efficacy of couple therapy where both partners were victims of chronic pain (Boyd, 2001). The sample included five couples. Treatment outcome was analyzed from the participants' responses. This istudy is useful in understanding the emotional and relational needs when both partners are afflicted with chronic pain disorders. All the couples received eight sessions of therapy, and the outcome was generally positive. In an earlier study I reported on the...

Proteasome Dependent Protein Degradation

Cachexia is frequently accompanied by elevated levels of proinflammatory cytokines 1-5 . Indeed, tumour necrosis factor-a (TNF-a) appears to play a key role in the development of this perturbation 6 . TNF-a was first described in 1975 and termed cachectin for its ability to induce weight loss and anorexia in mice 7 . This syndrome, however, was reversed when the injection of TNF-a was discontinued. In chronic heart failure, for example, which often leads to cardiac cachexia, TNF-a leads to reduced peripheral blood flow 8 , increased apop-

Culturebound Syndromes

Because theories of human functioning are culture-bound, our current diagnostic system for mental health problems is heavily culturally influenced (Paniagua, 2001 D. W. Sue et al., 1996). In addition, the manifestation of mental angst and distress occurs through different culturally specific symptom complexes that change over time. For example, in contrast to Freud's era (Jones, 1955), not many women in the United States currently have vapors or fainting spells however, eating disorders were almost unheard of a hundred years ago. Posttraumatic stress symptoms reflect at least some common human responses to trauma across cultures, but the name of the disorder has varied over many centuries. In addition, to some extent, what is actually considered traumatic is culturally specific, and what to do in the face of trauma constitutes culturally informed advice.

Reinforcement Value of Food

The effects of food deprivation, since responding for food went down rather than up. Other evidence from these experiments suggested that the effects of exercise were similar to the effects when feeding the animal. This finding is important for understanding activity anorexia, since exercise appears to substitute for eating.

The Biological Context of Eating and Activity

A major problem for an evolutionary analysis of activity anorexia is accounting for the decreased appetite of animals who travel to a new food patch. The fact that increasing energy expenditure is accompanied by decreasing caloric intake seems to violate common sense. From a homeostatic (i.e., energy balance) perspective, food intake and energy expenditure should be positively related. In fact, this is the case if an animal has the time to adjust to a new level of activity and food supply is not greatly reduced.

Alphaglucosidase inhibitor blocks hydrolysis of an

Anions (negative ions) anorexia - loss of appetite antecubital fossa - area in the crook of the arm anthropometric - literally means the measure of man type of measurement also referred to as body composition analysis antibody - an immunoglobulin produced by a B lymphocyte in response to a unique antigen antibody titer - measure of the amount of antibody

Dose administration malaise myalgias fatigueDLT for lowdose administration

-mucocutaneous effects (stomatitis, mucositis) -cardiovascular effects (arrhythmias, hypotension) -anorexia -anorexia, nausea and vomiting -alopecia Dexamethasone -corticosteroid -leukocytosis -nausea and vomiting -anorexia or increased appetite -CNS effects (psychosis, confusion) -fluid retention -hyperglycemia -osteoporosis

Lapatinib In Clinical Studies

Rash, nausea, diarrhea, fatigue, and anorexia. In a randomized, multicenter, phase IB study of lapatinib in patients with EGFR- and or HER2-overexpressing advanced solid tumors, four patients achieved a partial response from the 30 patients with pretreated MBC (49). Biological response assessment in those that achieved a PR showed significant decline in phosphorylated EGFR and HER2 as well as in phosphorylated downstream signal transducers, namely Akt and Erk. These changes correlated with increased tumor cell apoptosis as assessed by TUNEL analysis.

Historical Context

Cancer is a leading cause of death in Americans, second only to heart disease. While breast cancer kills the most women, many gynecological cancers are part of the overall cancer statistic. Ovarian cancer, the so-called whispering disease because of its insidious nature, is detected in one in 70 predominantly perimenopausal and postmenopausal American women and often metastasizes undetected. Risk factors include family history of ovarian and breast cancer, high dietary fat, delayed menopause, and no or late childbearing. The use of oral contraceptives appears to decrease risk. Ovarian cancer often presents itself with a cluster of three persistent and severe symptoms a swollen abdomen, a bloated feeling, and urgent urination. Other symptoms associated with the disease include gas pains, anorexia, backache, and indigestion. Unfortunately most women seek medical advice when their ovarian cancer is in the advanced stage because the symptoms might be associated with other gynecological...

Motivational Basis of Eating and Running

In Chapter 7, we discussed the interrelations of eating and running (Pierce et al., 1986). Recall that the research evidence indicates that rats will work more for an opportunity to run on a wheel as food deprivation increases. The animals bar pressed many more times for 60 s of wheel running as their body weights declined. Additionally, rats pressed a lever for food less when they had run on a wheel the night before a food session. This effect occurred even though the animals had several hours of rest before being placed in the operant chamber. The overall findings suggest that the reinforcing effectiveness of physical activity increased as a function of food deprivation. Also, the reinforcement value of eating food decreased when preceded by a bout of physical activity. These two reinforcement relations provide a behavioral account of the activity-anorexia cycle (see Chapter 7 for the biological basis of these reinforcement relationships).

Assessment Treatment and Prevention

The activity-anorexia model has important practical implications. In the book Solving the Anorexia Puzzle A Scientific Approach, Epling and Pierce (1992) outlined the criteria for assessment, treatment, and prevention of activity anorexia. In terms of assess ment, the primary criteria involve a history of low and declining food intake, a history of excessive physical activity, and psychological symptoms that follow rather than precede weight loss. Treatment is based on traditional behavior-modification procedures but is directed at the responses that compose the activity-anorexia cycle. For example, contingencies are arranged to stop excessive dieting and exercise. In addition, patients are taught how to eat and to discriminate between moderate and excessive levels of exercise. Prevention of activity anorexia involves changing the sociocultural conditions that promote excessive dieting and exercising. Medical doctors are in the best position to call attention to the role of diet and...

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