Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cachexia-anorexia syndrome occurs in chronic pathophysiologic processes including cancer, infection with human immunodeficiency virus, bacterial and parasitic diseases, inflammatory bowel disease, liver disease, obstructive pulmonary disease, cardiovascular disease, and rheumatoid arthritis. Cachexia makes an organism susceptible to secondary pathologies and can result in death. Cachexia-anorexia may result from pain, depression or anxiety, hypogeusia and hyposmia, taste and food aversions, chronic nausea, vomiting, early satiety, malfunction of the gastrointestinal system (delayed digestion, malabsorption, gastric stasis and associated delayed emptying, and/or atrophic changes of the mucosa), metabolic shifts, cytokine action, production of substances by tumor cells, and/or iatrogenic causes such as chemotherapy and radiotherapy. The cachexia-anorexia syndrome also involves metabolic and immune changes (mediated by either the pathophysiologic process, i.e., tumor, or host-derived chemical factors, e.g., peptides, neurotransmitters, cytokines, and lipid-mobilizing factors) and is associated with hypertriacylglycerolemia, lipolysis, and acceleration of protein turnover. These changes result in the loss of fat mass and body protein. Increased resting energy expenditure in weight-losing cachectic patients can occur despite the reduced dietary intake, indicating a systemic dysregulation of host metabolism. During cachexia, the organism is maintained in a constant negative energy balance. This can rarely be explained by the actual energy and substrate demands by tumors in patients with cancer. Overall, the cachectic profile is significantly different than that observed during starvation. Cachexia may result not only from anorexia and a decreased caloric intake but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions). In any case, the major deficit of a cachectic organism is a negative energy balance. Cytokines are proposed to participate in the development and/or progression of cachexia-anorexia; interleukin-1, interleukin-6 (and its subfamily members such as ciliary neurotrophic factor and leukemia inhibitory factor), interferon-gamma, tumor necrosis factor-alpha, and brain-derived neurotrophic factor have been associated with various cachectic conditions. Controversy has focused on the requirement of increased cytokine concentrations in the circulation or other body fluids (e.g., cerebrospinal fluid) to demonstrate cytokine involvement in cachexia-anorexia. Cytokines, however, also act in paracrine, autocrine, and intracrine manners, activities that cannot be detected in the circulation. In fact, paracrine interactions represent a predominant cytokine mode of action within organs, including the brain. Data show that cytokines may be involved in cachectic-anorectic processes by being produced and by acting locally in specific brain regions. Brain synthesis of cytokines has been shown in peripheral models of cancer, peripheral inflammation, and during peripheral cytokine administration; these data support a role for brain cytokines as mediators of neurologic and neuropsychiatric manifestations of disease and in the brain-to-peripheral communication (e.g., through the autonomic nervous system). Brain mechanisms that merit significant attention in the cachexia-anorexia syndrome are those that result from interactions among cytokines, peptides/neuropeptides, and neurotransmitters. These interactions could result in additive, synergistic, or antagonistic activities and can involve modifications of transducing molecules and intracellular mediators. Thus, the data show that the cachexia-anorexia syndrome is multifactorial, and understanding the interactions between peripheral and brain mechanisms is pivotal to characterizing the underlying integrative pathophysiology of this disorder.
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PMID:Central nervous system mechanisms contributing to the cachexia-anorexia syndrome. 1105 8

Palliative care patients present with multiple symptoms other than pain and cachexia. Asthenia, delirium, dyspnea, and chronic nausea and constipation cause significant distress to patients and families and frequently coexist in the same patient. A careful assessment frequently identifies reversible causes. When none are identified or there is no improvement, symptomatic pharmacologic interventions are available. The success rate is variable, and it is very high for symptoms such as chronic nausea or constipation and less effective for symptoms such as asthenia and delirium. More research on the mechanism and treatment of these symptoms is needed.
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PMID:Pharmacologic management of nonpain symptoms in surgical patients. 1140 53

Physical symptoms other than pain often contribute to suffering near the end of life. In addition to pain, the most common symptoms in the terminal stages of an illness such as cancer or acquired immunodeficiency syndrome are fatigue, anorexia, cachexia, nausea, vomiting, constipation, delirium and dyspnea. Management involves a diagnostic evaluation for the cause of each symptom when possible, treatment of the identified cause when reasonable, and concomitant treatment of the symptom using nonpharmacologic and adjunctive pharmacologic measures. Part I of this two-part article discusses fatigue, anorexia, cachexia, nausea and vomiting. Fatigue is the most common symptom at the end of life, but little is known about its pathophysiology and specific treatment. Education of the patient and family is the foundation of treatment with the possible use of adjunctive psychostimulants. Anorexia and cachexia caused by wasting syndromes are best managed with patient and family education, as well as a possible trial of appetite stimulants such as megestrol or dexamethasone. For appropriate pharmacologic treatment, it is helpful to identify the pathophysiologic origin of nausea in each patient.
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PMID:Management of common symptoms in terminally ill patients: Part I. Fatigue, anorexia, cachexia, nausea and vomiting. 1156 72

Cancer cachexia generally is considered to be the end stage in the progression of nutritional deterioration and wasting of malignancy (Ottery, 1995). In patients with advanced cancer, this condition is very common and decreases quality of life, as well as survival (Fearon et al., 2001; Ottery; Smith & Souba, 2001; Whitman, 2000). However, if early diagnosis and intervention can control cachexia, the potential exists to greatly improve a patient's quality of life and prolong survival. Because metabolic alterations inhibit the effective use of conventional nutritional support, anti-inflammatory agents or fish oil are possible options. Orexigenic agents may be prescribed if patients wish to improve oral intake. Steroids and progestational agents may be used to attempt to improve mood and appetite. Nutrition affects symptoms that need to be managed effectively. Nurses should work aggressively to correct factors that contribute to decreased food intake (e.g., nausea, pain) and correct factors that worsen debility (e.g., anemia). Information must be presented so that informed choices can be made and realistic eating goals set. An interdisciplinary approach that involves the nurse, physician, dietician, and possibly social worker or case manager, as well as the patient and family, is necessary to identify nutritional alterations, assess specific needs, and plan individual interventions. Whitman (2000) stated that counseling is the most effective and least expensive intervention. It may be conducted by any member of the healthcare team and should be combined with other interventions. Palliation of cachexia in patients with advanced cancer is a challenge for nurses. Hopefully, early and judicious use of these interventions may decrease the significant morbidity and mortality that result from cancer cachexia.
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PMID:Cachexia in patients with advanced cancer. 1208 22

Parathyroid hormone-related protein (PTHrP) plays a central role in humoral hypercalcemia of malignancy (HHM), which is one of the most frequent paraneoplastic syndromes. PTHrP produced by the tumor acts through a common PTH/PTHrP receptor to promote bone resorption, inhibit calcium excretion from the kidney, and induce hypercalcemia. Patients with HHM often develop cachexia associated with typical symptoms such as anorexia, malaise, nausea, constipation, polyuria, polydipsia, and confusion. The etiology of the cachexia is not fully understood but is thought to be caused by hypercalcemia and various cytokines such as interleukin-6, tumor necrosis factor-alpha, leukemia inhibitory factor, and others. In this study, we investigated the role of PTHrP in hypercalcemia and cachexia in HHM by using humanized anti-PTHrP antibody. A mouse monoclonal antibody that binds to PTHrP amino acid sequence 1-34 and inhibits PTHrP function has been humanized to create a specific and potent agent for the treatment of patients with HHM. The mouse monoclonal antibody has been shown to have antihypercalcemic activity against nude mice bearing human tumors. Because a mouse antibody is highly immunogenic in human patients, the complementarity-determining regions from the mouse antibody were grafted into a human antibody. The resulting humanized antibody specifically recognizes PTHrP(1-34) and neutralizes PTHrP functions in vitro and in vivo. The humanized anti-PTHrP antibody was administered intravenously to HHM model animals bearing tumors such as LC-6 human lung carcinoma. These animals showed symptoms similar to those of patients with HHM (eg, hypercalcemia and cachexia). The humanized anti-PTHrP antibody-treated animals responded with normalization of blood ionized calcium level through an improvement of bone metabolism and calcium excretion. Moreover, the treated animals also showed an improvement in body weight, ultromotivity, metabolic alkalosis, food consumption, water intake, serum phosphorus, and renal function. Consequently, the humanized antibody-treated animals experienced complete resolution of hypercalcemia and cachexia. These results suggest that the humanized antibody would be an effective and beneficial agent for patients with HHM, and that PTHrP is a major pathogenetic factor of hypercalcemia and cachexia in patients with HHM.
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PMID:Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody. 1461 38

Systemic syndromes characterized by a persistent activity of circulating mediators (cytokines) are frequently present with advanced cancer. We grouped under the general heading of "Systemic Immune-Metabolic Syndrome (SIMS)" a particular variety of distressing systemic syndrome characterized by dysregulation of the psycho-neuro-immune-endocrine homeostasis, with overlapping clinical manifestations. SIMS may include cachexia, anorexia, nausea, early satiety, fatigue, tumor fever, cognitive changes and superinfection. The aim of this study was to ameliorate some of the SIMS symptoms in a homogeneous group of lung adenocarcinoma patients using a multitargeted therapy. Fifteen patients with evidence of SIMS were studied. SIMS was defined as the presence of weight loss, anorexia, fatigue performance status>/=2 and acute-phase protein response. Patients received medroxyprogesterone (MPA) (500 mg twice daily), celecoxib (200 mg twice daily), plus oral food supplementation for 6 weeks. After treatment, 13 patients either had stable weight (+/- 1%) or had gained weight. There were significant differences in improvement of body-weight-change rate, nausea, early satiety, fatigue, appetite and performance status. Patients who had any kind of lung infection showed higher levels of IL-10 compared to non-infected patients (P=0.039). Our results suggest that patients with advanced lung adenocarcinoma, treated with MPA, celecoxib and dietary intervention, might have considerable improvement in certain SIMS outcomes. This multitargeted symptomatic approach deserves further study.
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PMID:Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study. 1533 28

Thalidomide was first produced in Germany in the 1950s. The drug was promoted as a safe sedative and was found to be useful as an antiemetic during pregnancy. In late 1960s, reports of teratogenic actions resulted in the withdrawal of thalidomide from world markets. Thalidomide has multiple actions, including anti-inflammatory and anti-angiogenic ones. This article reviews the pharmacology and clinical trials of the drug for the treatment of various cancers including multiple myeloma. Furthermore, in preliminary studies, thalidomide has been found to be effective in several syndromes related to advanced cancer, such as the cancer cachexia, chronic nausea and pain.
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PMID:[Thalidomide--new prospective therapy in oncology]. 1504 11

The incidence of pancreatic cancer is about 10,000 cases a year in Germany. The role of surgery as a curative modality is limited. The 5-year survival for all stages remains less than 5%. Pain, cachexia, jaundice, nausea, fatigue and depression are frequent symptoms which reduce the quality of life for affected patients. Therefore, amelioration of symptoms is a major goal of palliative care. Chemotherapy may yield a moderate survival benefit. Gemcitabine is the drug of choice in metastatic pancreatic cancer. In locally advanced disease, radiochemotherapy can be considered. Different treatment strategies against molecular targets are currently tested in clinical trials.
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PMID:[Best supportive care of pancreatic carcinoma]. 1516 Feb 43

Many patients with life-threatening diseases such as cancer experience severe symptoms that compromise their health status and deny them quality of life. Patients with cancer often experience cachexia, pain, and depression,which translate into an unacceptable quality of life. The discovery of the endocannabinoid system has led to a renewed interest in the use of cannabinoids for the management of nausea, vomiting, and weight loss arising either from cancer or the agents used to treat cancer. The endocannabinoid system has been found to be a key modulator of systems involved in pain perception, emesis, and reward pathways. As such, it represents a target for development of new medications for controlling the symptoms associated with cancer. Although the cannabinoid receptor agonist tetrahydrocannabinol and one of its analogs are currently the only agents approved for clinical use, efforts are under way to devise other strategies for activating the endocannabinoid system for therapeutic uses.
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PMID:Mechanism of action of cannabinoids: how it may lead to treatment of cachexia, emesis, and pain. 1535 14

Delta-9-tetrahydrocannabinol (THC) is increasingly used for the long-term treatment of nausea, vomiting, cachexia, and chronic pain. Recent reports, however, have indicated an increased risk of myocardial infarction and thromboangiitis obliterans after THC intake. Blood platelets have an essential role in the pathogenesis of these two diseases, but it is unclear whether platelets are potential target cells for cannabinoids. We investigated the effects of THC on human platelets and the expression of cannabinoid receptors on their cell membranes in this in vitro study. The effects of THC (final concentrations 10(-7) to 10(-5) M) on the expression of activated platelet fibrinogen receptor (glycoprotein IIb-IIIa) and P selectin were characterized by flow cytometry. Western blotting was performed with platelet membrane preparations to determine the surface expression of cannabinoid receptors on human platelets. THC increased the expression of glycoprotein IIb-IIIa and P selectin on human platelets in a concentration-dependent manner. The two known cannabinoid receptors (CB(1) and CB(2)) were both detected on the cell membrane of human platelets. Our functional results may suggest a receptor-dependent pathway of THC-induced platelet activation. However, further in vivo studies are warranted to evaluate the role of cannabinoid receptors in mediating the demonstrated procoagulatory effect of THC.
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PMID:The procoagulatory effects of delta-9-tetrahydrocannabinol in human platelets. 1538 62


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