Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
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Pellagra is a systemic disturbance caused by a cellular deficiency of niacin, resulting from inadequate dietary nicotinic acid and/or its precursors, the essential amino-acid tryptophan. In Europe and North America cases of pellagra are rarely encountered, but in some developing countries this disease is frequent, and is the most frequent clinical feature of nutritional deficiency of adult. The principal causes of pellagra are: nutritional niacin deficiency; chronic alcoholism; gastro-intestinal malabsorption; some medications (5-fluoro-uracil, isoniazid, pyrazinamide ehtionamide, 6-mercaptopurine, hydantoins, phenobarbital and chloramphenicol). The diagnosis of pellagra is based on the patient's history and the presence of "3 D syndrome": dermatitis, diarrhea, and dementia. The dermatitis caused by pellagra is a bilaterally symmetrical erythema at the sites of solar exposure. The dermatitis begins in the form of an erythema with acute or intermittent onset gradually changing to an exsudative eruption on the dorsa of the hand, face, neck, and chest with pruritus and burning. Acute dermatitis of pellagra resembles sunburn in the first stages, sometimes with vesicles and bullae. The gastro-intestinal disturbances are: anorexia, nausea, epigastric discomfort and chronic or recurrent diarrhea. Anorexia and malabsorbative diarrhea lead to a state of malnutrition and cachexia. Stools are typically watery, but occasionally can be bloody and mucoid. Neuropsychologic manifestation included photophobia, asthenia, depression, hallucinations, confusions, memory loss and psychosis. As pellagra advances, patient become disoriented, confused and delirious; then stuporous and finally die. Pathological changes in the skin is non-specific, there are no chemical tests available to definitively diagnose pellagra. However low levels of urinary excretion of N-methylnicotinamide and pyridone indicates niacin deficiency. The treatment of pellagra consisted to exogenous administration of niacin or nicotinamide cures. Topical management of skin lesions with emollients may reduce discomfort. The therapy should also include other B vitamins, zinc and magnesium as well as a diet rich in calories. The prevention is based in the nutritional education (food sources of niacin: eggs, bran, peanuts, meat, poultry, fish, red meat, legumes and seeds), and the eviction of alcohol.
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PMID:[Pellagra]. 1620 85

Anorexia and appetite assessment is an important priority in supportive oncology. A series of 156 veterans participating in a hematology oncology service completed the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), the Functional Assessment of Cancer Therapy-General scale, the Memorial Symptom Assessment Scale Short Form (MSAS-SF), and the Zung Self-Rating Depression Scale and were followed for survival. The FAACT score correlated well with Karnofsky performance status, quality of life, and symptom distress subscales. A single appetite distress item from the MSAS-SF correlated well with these measures. Both appetite measures correlated with the presence of other symptoms and with concurrently measured hemoglobin, serum sodium, albumin, and cholesterol levels. These self-reported appetite measures were univariate predictors of survival and contributed additional prognostic information to data related to weight-loss distress. In a smaller study, the FAACT score correlated with a visual analogue measure of appetite and with the North Center Cancer Treatment Group appetite instrument. These data support use of these tools for the evaluation of appetite concerns among patients with advanced cancer.
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PMID:The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) Appetite Scale in veteran cancer patients. 1621 62

Cancer-associated malnutrition can result from local effects of a tumour, the host response to the tumour and anticancer therapies. Although cancer patients often have reduced food intake (due to systemic effects of the disease, local tumour effects, psychological effects or adverse effects of treatment), alterations in nutrient metabolism and resting energy expenditure (REE) may also contribute to nutritional status. Several agents produced by the tumour directly, or systemically in response to the tumour, such as pro-inflammatory cytokines and hormones, have been implicated in the pathogenesis of malnutrition and cachexia. The consequences of malnutrition include impairment of immune functions, performance status, muscle function, and quality of life. In addition, responses to chemotherapy are decreased, chemotherapy-induced toxicity and complications are more frequent and severe, and survival times are shortened. Depression, fatigue and malaise also significantly impact on patient well-being. In addition, cancer-related malnutrition is associated with significant healthcare-related costs. Nutritional support, addressing the specific needs of this patient group, is required to help improve prognosis, and reduce the consequences of cancer-associated nutritional decline.
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PMID:The causes and consequences of cancer-associated malnutrition. 1643 58

Toxic neutrophils exhibit a variety of nuclear and cytoplasmic abnormalities in Romanowsky-stained blood smears, and are associated with inflammation and infection. The purpose of the retrospective study reported here was to investigate the association of toxic neutrophils with clinicopathologic characteristics, diseases, and prognosis in cats. Cats with toxic neutrophils (n = 150) were compared with negative-control cats (n = 150). Statistical analyses included Fisher exact, independent t-, nonparametric Mann-Whitney, and chi-squared tests. Cats with toxic neutrophils had significantly (P < .05) higher prevalence of fever, icterus, vomiting, diarrhea, depression, dehydration, weakness, and cachexia, as well as leukocytosis, neutrophilia, left shift, neutropenia, anemia, hypokalemia, and hypocalcemia. The prevalence of shock, sepsis, panleukopenia, peritonitis, pneumonia, and upper respiratory tract diseases was significantly higher among these cats, as were infectious (viral and bacterial) and metabolic disorders. Control cats had a significantly higher prevalence of feline asthma, as well as allergic, idiopathic, and vascular disorders. Hospitalization duration and treatment cost were significantly (P < .001) higher in cats with toxic neutrophils. In 53 and 47% of the cats with toxic neutrophils, the leukocyte and neutrophil counts were normal, respectively, whereas in 43%, both abnormalities and left shift were absent, and toxic neutrophils were the only hematologic evidence of inflammation or infection. In conclusion, toxic neutrophils were found to be associated with certain clinicopathologic abnormalities, and when present, may aid in the diagnosis, as well as the assessment of hospitalization duration and cost. The evaluation of blood smears for toxic neutrophils provided useful clinical information.
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PMID:Toxic neutrophils in cats: clinical and clinicopathologic features, and disease prevalence and outcome--a retrospective case control study. 1649 19

Anorexia is one of the most common symptoms of patients with advanced cancer and it presents as loss of appetite due to satiety. On the other hand, cachexia is described in those patients with unwanted weight loss. Cancerous processes produce an energy unbalance by decreased food intake and increased catabolism, resulting in a clearly negative balance. Several factors determining cachexia are observed, from metabolic unbalances produced by tumoral products and endocrine impairments or the inflammatory response produced by cytokines, all of them leading to higher lipolysis, loss of muscle protein, and anorexia. Besides, causes of anorexia are multiple, from chemotherapy agents, radiotherapy, or immunotherapy, which may produce different degrees of nausea, vomiting, diarrhea, and also leading to impairments of taste and smell, to obstruction of the digestive tract, pain, depression, constipation, etc. From the knowledge of the different mechanisms producing the anorexia-cachexia syndrome, hypercaloric diets for artificial nutrition have been studied with varying success, and different drugs with a positive effect on appetite gain such as progestogens, steroids, and with lesser clinical evidence cannabinoids, cyproheptadine, mirtazapine (antidepressant), and olanzapine (antipsychotic). Other drugs have been studied because of their anti-inflammatory properties, anti-cytokine, such as melatonin, polyunsaturated omega-3 fatty acids, pentoxifylline, and thalidomide; with the exception of the latter, clinical data are still scant for daily usage. Similarly happens with testosterone-derived anabolic drugs or with metabolism inhibitors such as hydrazine sulfate. With no doubt, progestogens, especially megestrol, and corticosteroids will be first-line therapies for anorexia-cachexia syndrome to stimulate the appetite and increase weight (megestrol), and have an effect on quality of life improvement and comfort in patients with advanced cancer.
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PMID:[Pharmacological therapy of cancer anorexia-cachexia]. 1676 27

This study involved longitudinal evaluations of symptom severity and describes the symptom patterns of 77 terminal cancer patients (median age: 62 years; 61% female), selected from 537 consecutive patients admitted to the Palliative Care Unit of the National Taiwan University Hospital. The most common primary cancer sites in these patients were lung (23.4%), liver (15.6%), and stomach (13%). Nineteen physical and psychological symptoms were assessed using different scales. The median number of symptoms was 11 (range: 1-18) on admission, among which weakness, fatigue, anorexia, pain, and depression were the most common. A comparison of the initial symptom severity scores with those at one week after admission and two days before death suggested six symptom change patterns: A: continuous static (restless/heat, abdominal fullness, constipation, dizziness, and insomnia); B: static-increase (fatigue, weakness, nausea/vomiting, taste alteration, dysphagia, diarrhea, dry mouth, and night sweats); C: decrease-static (pain and depression); D: decrease-increase (anorexia and dyspnea); E: static-decrease (aggression); and F: gradually decrease (anxiety). These six symptom patterns can be divided into two categories on the basis of the relative severity of symptoms between one week after admission and two days before death. The first category included patterns A, C, E and F, and the symptoms improved with palliative care. However, the symptoms in the second category (patterns B and D), which were associated with the anorexia-cachexia syndrome and dyspnea, did not show improvement. As symptom management is an essential component of palliative care, holistic care, which encompasses physical, psychosocial and spiritual aspects, represents a rational approach for the relief of these incurable symptoms at the end stage of life for these patients.
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PMID:Symptom patterns of advanced cancer patients in a palliative care unit. 1706 Feb 55

An outbreak of a previously unreported disease affecting southern chamois (Rupicapra pyrenaica) in the central Pyrenees (NE Spain) was recorded in 2001 and 2002. There was a marked temporal distribution, most animals being found between February and June. After the outbreak, the population was found to have decreased by about 42%, most probably due to the disease. We examined 20 affected chamois. Clinical manifestations included depression, weakness and movement difficulties in all cases. Three chamois presented abnormal behaviour, with absence of flight reaction, and 16 showed different degrees of alopecia with skin hyperpigmentation. At necropsy cachexia was observed in all animals, four chamois had abscesses in different parts of the body, four had pneumonia, one had an extensive subcutaneous infection on the head and neck and one had severe orchitis. Microscopic lesions were found in the brain, mainly edema, gliosis, espongiosis, cariorrexis and neuronal multifocal necrosis. A perivascular mononuclear inflammatory infiltrate was present in three of them. Skin lesions included marked follicular atrophy, mild to moderate epidermal hyperplasia with orthokeratotic hyperkeratosis and follicular hyperkeratosis, and hypermelanosis. In 13 chamois there were haemosiderin deposits in the spleen, and in three individuals kidney "cloissone" was observed. Intraeritrocitic parasites were detected either by direct observation or PCR in 8 of 17 chamois. A pestivirus was isolated and detected by RT-PCR from 12 of 13 affected chamois and antigenic characterized as border disease virus by monoclonal antibodies. This is the first time a border disease virus has been associated with an outbreak of a high-mortality disease in a wild species.
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PMID:Severe outbreak of disease in the southern chamois (Rupicapra pyrenaica) associated with border disease virus infection. 1710 Dec 42

Weight loss in older persons is associated with a variety of deleterious effects, including hip fracture, pressure ulcers, decreasing immune function, decreased functional status, and death. There are 4 major causes of weight loss: anorexia, sarcopenia, cachexia, and dehydration. Many of the reasons for the development of these conditions are treatable. For example, depression is the most common cause of weight loss in the elderly. Early screening for anorexia can be undertaken in the physician's office utilizing the Simplified Nutritional Assessment Questionnaire. An algorithmic approach to the office management of weight loss is provided.
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PMID:Office management of weight loss in older persons. 1714 41

Both proteolysis-inducing factor (PIF) and angiotensin II have been shown to produce a depression in protein synthesis in murine myotubes concomitant with an increased phosphorylation of eukaryotic initiation factor 2 (eIF2alpha). Both PIF and angiotensin II were shown to induce autophosphorylation of the RNA-dependent protein kinase (PKR), and an inhibitor of this enzyme completely attenuated the depression in protein synthesis and prevented the induction of eIF2alpha phosphorylation. The PKR inhibitor also completely attenuated the increase in protein degradation induced by PIF and angiotensin II and prevented the increase in proteasome expression and activity. To confirm these results myotubes were transfected with plasmids that express either wild-type PKR, or a catalytically inactive PKR variant, PKRDelta6. Myotubes expressing PKRDelta6 showed no increase in eIF2alpha phosphorylation in response to PIF or angiotensin II, no depression in protein synthesis, and no increase in protein degradation or increase in proteasome expression. Induction of the ubiquitin-proteasome pathway by PIF and angiotensin II has been linked to activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Inhibition of PKR prevented nuclear migration of NF-kappaB in response to both PIF and angiotensin II, by preventing degradation of the inhibitor protein I-kappaB. Phosphorylation of PKR and eIF2alpha was also significantly increased in the gastrocnemius muscle of weight losing mice bearing the MAC16 tumor, suggesting that a similar process may be operative in cancer cachexia. These results provide a link between the depression of protein synthesis in skeletal muscle and the increase in protein degradation.
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PMID:Skeletal muscle atrophy, a link between depression of protein synthesis and increase in degradation. 1721 91

Pancreatic cancer is one of the most lethal malignancies. An estimated 32,300 patients will die of pancreatic cancer in year 2006. It is the tenth most common malignancy in the United States. Despite recent advances in pathology, molecular basis and treatment, the overall survival rate remains 4% for all stages and races. Palliative care represents an important aspect of care in patient with pancreatic malignancy. Identifying and treating disease related symptomology are priorities. As a physician taking care of these patients it is essential to know these symptoms and treatment modalities. This review discusses symptom management and supportive care strategies. Common problems include pain, intestinal obstruction, biliary obstruction, pancreatic insufficiency, anorexia-cachexia and depression. Success is needed in managing these symptoms to palliate patients with advanced pancreatic cancer. Pancreatic cancer is a model illness to learn the palliative and supportive management in cancer patient. It is important for oncologists to recognize the importance of control measures and supportive measures that can minimize the symptoms of advanced disease and side effects of cancer treatment.
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PMID:Supportive and palliative care of pancreatic cancer. 1735 51


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