Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CACHEXIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1999

Anthropometric evaluation of cachexia in chronic congestive heart failure: the role of tricuspid regurgitation.

Cardiac cachexia has recently been identified as an independent risk factor for mortality in chronic congestive heart failure. The aims of our study were to further identify the clinical or biochemical predictors or correlates of the cachexia, and to quantitate the magnitude of wasting. We undertook an anthropometric comparison of 30 patients with congestive heart failure, aged 56 (13) years, with ten age- and sex-matched healthy volunteers and 16 patients with essential hypertension. In comparison to the healthy volunteers, the heart failure patients exhibited a trend towards a lower body mass index, 21 (2.7) versus 23 (3.8) kg/m2, the 95% confidence interval for the difference being -0.54 to 5.4. However, the mid-upper arm circumference, of 24 (3.8) cm in the heart failure patients, was significantly (P<0.02) lower than the 27 (2.0) cm in the healthy volunteer group, with a 95% confidence interval for the difference being 1.18 to 4.82 cm. The triceps, mid-thigh, scapula and abdominal skinfold thicknesses were separately and significantly (P<0.05) diminished in the heart failure patients compared to the healthy controls. The sum of the four skin fold thicknesses, with a value of 68 (13) mm in the healthy volunteers, was highly significantly greater (P<0.001) than the value of 35.6 (9) mm in the heart failure patients. The 95% confidence interval for this difference was 22.7 to 41.3 mm. The patients with essential hypertension differed significantly from the heart failure patients in all of these parameters (P<0.01), but were not statistically different from the healthy controls in the anthropometric parameters. Among the heart failure patients, those with tricuspid regurgitation (n = 12) had a worse clinical, biochemical and cachexia profile compared to patients without the tricuspid regurgitation (n = 18). The values (tricuspid regurgitation versus no regurgitation) were New York Heart Association Class, 3.5 (0.65) versus 2.7 (0.75), P<0.01; ejection fraction of 34 (9) versus 43 (13)%, not significant; greater hepatomegaly of 159 (31) versus 135 (29) mm, P<0.05; more severe hypoalbuminemia, 24.5 (2.7) versus 28.5 (6.8) g/l, P<0.05; and worse hyponatremia, 128 (4) versus 133 (5) mmol/l, P<0.05. The tricuspid regurgitation group had a significantly more severe reduction in abdominal and scapula skin fold thickness (P<0.01) than that found in patients without tricuspid regurgitation. The sum of the four skin fold thicknesses was significantly lower (P<0.05) in tricuspid regurgitation, 30.9 (8) mm, than in heart failure without associated regurgitation, 38.0 (9.6). The 95% confidence interval for the difference was 0.8 to 13.4 mm. It is concluded that significant diminution of muscle bulk and subcutaneous fat occurs in chronic heart failure. Tricuspid regurgitation may be an accentuating and accelerating risk factor for cardiac cachexia, on account of a greater hypoalbuminemia and hyponatremia, which, presumably, results from the associated protein-losing enteropathy.

Anthropometry↗
PubMed2002

Distinguishing starvation from cachexia.

The poor response to hypercaloric feeding in ill adults may be caused by failure to distinguish cachexia from starvation (Table 1). The chief difference between starvation and cachexia is that refeeding reverses starvation but is less effective for cachexia. The ineffectiveness of refeeding in treating cachexia may explain some of the poor results from direct nutritional interventions in clinical trials. Simple starvation should respond to voluntary or involuntary hypercaloric feedings. The failure to demonstrate a more positive response may be caused by underlying cachexic states.

Aged↗
PubMed1995

Anorexia, cachexia, and dysphagia: the symptom experience.

OBJECTIVES: To review the symptoms of anorexia, cachexia, and dysphagia and to provide information on nutritional assessment and interventions. DATA SOURCES: Published studies of anorexia, cachexia, and dysphagia, research abstracts, and review articles. CONCLUSIONS: Anorexia, cachexia, and dysphagia can cause severe alterations in nutrition in cancer patients that may lead to irreversible nutritional compromise and death. Nursing research must focus on symptom management of these three symptoms, the needs of the patient and family, and the impact of dysphagia on quality of life. IMPLICATIONS FOR NURSING PRACTICE: Assessment, objective evaluation, pharmacological interventions, and nutritional counseling are important interventions for patients with anorexia and cachexia. Swallowing therapy, food intake adjustments, oral hygiene, and supportive care are important measures needed by the patient with dysphagia.

Anorexia↗
PubMedDate not supplied

Cachexia in experimental models.

Cachexia refers to a state of severe malnutrition characterized by anorexia, weight loss, and muscle wasting. Although it is most commonly considered in the context of cancer, it may occur as a consequence of a variety of chronic diseases. Cachexia appears to differ from "semistarvation" in that there is evidence of metabolic changes that are different from the normal response to reduce food intake. Animal models are useful in the study of cachexia because they allow homogeneous groups of subjects, free from confounding influences, to be studied. Accurate control of diet is possible, and pair-fed controls can be used to allow specific investigation of the metabolic component. However, the model must show features that are appropriate for the disease being studied. In the case of cancer this means using a model in which cachexia occurs without too high a tumor burden or growth rate or too severe a reduction in food intake. Studies in the author's laboratory have used a transplantable Leydig cell tumor in Fischer rats. Food intake decreases by 20-40% and energy expenditure is greater than that of pair-fed controls. One mechanism that may be responsible for this relates to the postprandial metabolism of carbohydrate, since after a test meal there appears to be a greater rate of hepatic glycogen synthesis via the indirect pathway in tumor-bearing rats than in controls. The indirect pathway involves gluconeogenic enzymes, and studies using a variety of different tracers and enzyme inhibitors suggest that amino acids are important precursors. An increased rate of hepatic glycogen synthesis also appears to be maintained for a longer time after the meal in tumor-bearing rats, and this may act to delay the onset of the next meal, thereby explaining the decreased meal frequency that has been observed.

Animals↗
PubMed1999

Investigation of the potential of capillary electrophoresis with off-line matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for clinical analysis: examination of a glycoprotein factor associated with cancer cachexia.

The potential of capillary electrophoresis (CE) with offline matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry has been demonstrated for the examination of a glycoprotein factor associated with cancer cachexia. A comparison of CE profiles of a healthy volunteer and a cancer patient shows the presence of additional peaks in the electropherogram of the cancer patient that could be associated with cachexia. Micropreparative CE was performed with 180-micron fused silica capillary columns with tapered ends to collect CE fractions for further identification by MALDI-TOF-MS. The analysis of crude urine samples of cancer patients exhibiting cachexia, as well as CE fractions, with MALDI-TOF-MS using ferulic acid as the matrix shows a number of characteristic ions at m/z values of approximately 24 and approximately 67 kDa. The 24-kDa peak may be identified as the cachectic factor, a glycoprotein, whereas the peak at 67 kDa is identified as albumin, which is present in urine of most patients, and to which the cachectic factor is noncovalently bound. The combined use of CE and MALDI-TOF-MS was successful in detecting cachexia in all of the patients in this study, including one patient that was in an early phase of the disease.

Blood Proteins↗
PubMed2005

Therapy insight: Cancer anorexia-cachexia syndrome--when all you can eat is yourself.

Tumor growth is associated with profound metabolic and neurochemical alterations, which can lead to the onset of anorexia-cachexia syndrome. Anorexia is defined as the loss of the desire to eat, while cachexia results from progressive wasting of skeletal muscle mass--and to a lesser extent adipose tissue--occurring even before weight loss becomes apparent. Cancer anorexia-cachexia syndrome is highly prevalent among cancer patients, has a large impact on morbidity and mortality, and impinges on patient quality of life. However, its clinical relevance is frequently overlooked, and treatments are usually only attempted during advanced stages of the disease. The pathogenic mechanisms of cachexia and anorexia are multifactorial, but cytokines and tumor-derived factors have a significant role, thereby representing a suitable therapeutic target. Energy expenditure in anorexia is frequently increased while energy intake is decreased, which further exacerbates the progressive deterioration of nutritional status. The optimal therapeutic approach to anorectic-cachectic cancer patients should be based on both changes in dietary habits, achieved via nutritional counseling; and drug therapy, aimed at interfering with cytokine expression or activity. Our improved understanding of the influence a tumor has on the host's metabolism is advancing new therapeutic approaches, which are likely to result in better preservation of nutritional status if started concurrently with specific antineoplastic treatment.

Anorexia↗
PubMed1999

Tumour inoculation site-dependent induction of cachexia in mice bearing colon 26 carcinoma.

Murine colon 26 carcinoma growing at either subcutaneous (s.c.) or intramuscular (i.m.) inoculation sites causes cachexia in mice. Such animals show extensive loss of body weight, wasting of the muscle and adipose tissues, hypoglycaemia, and hypercalcaemia, even when the tumour weight comprises only about 1.9% of carcass weight. In contrast, the same tumour when inoculated into the liver does not cause any sign of tumour-related cachexia even when the tumour becomes much larger (6.6% of carcass weight). Interleukin 6 (IL-6), a mediator associated with cachexia in this tumour model, is detected at high levels both in the tumour tissues and in the circulating blood of mice bearing colon 26 tumour at the s.c. inoculation site. In contrast, only minute levels of IL-6 are detected in the tumour grown in the liver. The colon 26 tumour grown in the liver does not lose its ability to cause cachexia, because the tumour when re-inoculated s.c. is able to cause extensive weight loss and produce IL-6 as did the original colon 26 cell line. Histological studies revealed differences in the composition of tumour tissues: the tumours grown in the subcutis consist of many polygonal tumour cells, extended-intercellular space, and high vascular density, whereas those grown in the liver consist of spindle-shaped tumour cells. Thus, the environment where tumour cells grow would be a critical factor in determining the cachectic phenotype of cancer cells, including their ability to produce IL-6.

Animals↗
PubMed2006

Leptin and inflammation-associated cachexia in chronic kidney disease.

Leptin is an adipocyte-derived hormone that acts as a major regulator of food intake and energy homeostasis. It circulates both as a free and as a protein-bound entity. Leptin is released into the blood in proportion to the amount of body fat and exerts sustained inhibitory effects on food intake while increasing energy expenditure. The leptin receptor belongs to the class I cytokine receptor superfamily and possesses strong homology to the signal-transducing subunits of the IL-6 receptor. The hypothalamic melanocortin system, and specifically the melanocortin-4 receptor (MC-4R), is critical in mediating leptin's effect on appetite and metabolism. Serum leptin concentrations are elevated in patients with chronic kidney disease (CKD) and correlate with C-reactive protein levels suggesting that inflammation is an important factor that contributes to hyperleptinemia in CKD. Hyperleptinemia may be important in the pathogenesis of inflammation-associated cachexia in CKD. We showed that experimental uremic cachexia was attenuated in db/db mice, a model of leptin receptor deficiency. Nephrectomy in these animals did not result in any change in weight gain, body composition, resting metabolic rate, and efficiency of food consumption. Furthermore, experimental uremic cachexia could be ameliorated by blocking leptin signaling through the hypothalamic MC-4R. MC-4R knockout mice or mice administered the MC-4R and MC-3R antagonist, agouti-related peptide, resisted uremia-induced loss of lean body mass and maintained normal basal metabolic rates. Thus, melanocortin receptor antagonism may provide a novel therapeutic strategy for inflammation-associated cachexia in CKD.

Animals↗
PubMed2001

Cleavage of caspases-1, -3, -6, -8 and -9 substrates by proteases in skeletal muscles from mice undergoing cancer cachexia.

A prominent feature of several type of cancer is cachexia. This syndrome causes a marked loss of lean body mass and muscle wasting, and appears to be mediated by cytokines and tumour products. There are several proteases and proteolytic pathways that could be responsible for the protein breakdown. In the present study, we investigated whether caspases are involved in the proteolytic process of skeletal muscle catabolism observed in a murine model of cancer cachexia (MAC16), in comparison with a related tumour (MAC13), which does not induce cachexia. Using specific peptide substrates, there was an increase of 54% in the proteolytic activity of caspase-1, 84% of caspase-8, 98% of caspase-3 151% to caspase-6 and 177% of caspase-9, in the gastrocnemius muscle of animals bearing the MAC16 tumour (up to 25% weight loss), in relation to muscle from animals bearing the MAC13 tumour (1-5% weight loss). The dual pattern of 89 kDa and 25 kDa fragmentation of poly (ADP-ribose) polymerase (PARP) occurred in the muscle samples from animals bearing the MAC16 tumour and with a high amount of caspase-like activity. Cytochrome c was present in the cytosolic fractions of gastrocnemius muscles from both groups of animals, suggesting that cytochrome c release from mitochondria may be involved in caspase activation. There was no evidence for DNA fragmentation into a nucleosomal ladder typical of apoptosis in the muscles of either group of mice. This data supports a role for caspases in the catabolic events in muscle involved in the cancer cachexia syndrome.

Animals↗
PubMed1995

[Value of megestrol acetate in treatment of cachexia in head-neck tumors].

Mortality of 70% of all patients with tumors in the head and neck is linked with anorexia and cachexia. Two reasons for cachexia are well known: 1. local disease and local therapy preventing oral nutrition and 2. advanced tumors activating biochemical pathways of proteolysis, lipolysis, and gluconeogenesis. Five groups of substances are now used to treat tumor-induced cachexia: corticosteroids, progestational drugs, cyproheptadine, hydrazine sulfate, and anabolic steroids. Between 1992 and 1993 we treated 38 patients suffering from cachexia due to advanced cancers of the head and neck with 160 mg megestrol acetate per day for four months. The increase in body weight was significant after eight weeks. The mean increase after full therapy was 4.58 +/- 3.19 kg. Treatment of the five women in the series was very successful and all achieved their former body weight. Megestrol acetate therapy was best started after assuring enteral nutrition. Significant adverse events were loss of libido for the men, headache and, rarely, thrombophlebitis. Our first experiences suggest that megestrol acetate treatment is useful in cachectic patients with advanced squamous cell carcinomas of the head and neck.

Adult↗
PubMed1988

Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation.

Cachexia is a potentially lethal syndrome of unknown etiology characterized by anorexia, weight loss, and protein wasting that frequently complicates the treatment of chronic inflammation and cancer. Cachectin/TNF was isolated during the search for a humoral mediator of cachexia and found to stimulate the breakdown of energy stores from adipocytes and myocytes in vitro, but the chronic effects of the monokine in vivo are not known. Sublethal doses of recombinant human cachectin administered twice daily for 7-10 d caused cachexia in rats, as evidenced by reduced food intake, weight loss, and depletion of whole-body lipid and protein stores. Significant anemia is also observed and found to be the result of decreased red blood cell mass, not expanded plasma volume. Leukocytosis and histopathological evidence of tissue injury and inflammation are observed in several organs, including omentum, liver, spleen, and heart. These data suggests that the exposure of the normal host to cachectin is capable of inducing a pathophysiological syndrome of cachexia, anemia, and inflammation similar to that observed during inflammatory states or malignancy.

Anemia↗
PubMed1996

Fat malabsorption in elderly patients with cardiac cachexia.

Malnutrition resulting from chronic congestive heart failure (cardiac cachexia, CC) is not uncommon and contributes to mortality and morbidity especially of elderly people. The aetiology of cardiac cachexia is probably multifactorial. We have assessed whether malabsorption of fat is associated with CC and if so whether it is due to small-bowel bacterial overgrowth. Three groups of subjects were studied: 29 (20 women) patients (mean age 76.1 years) with controlled congestive heart failure and weight loss (CC); 14 (seven women) patients (mean age 74.0 years) with controlled congestive heart failure and no weight loss (non-cachexia, NON-CC); and 29 (20 women) healthy controls (mean age 74.9 years). Fast absorption was quantified using the cumulative 6 h 14CO2 exhalation in the 14C-triolein breath test and small-bowel bacterial overgrowth was quantified using the cumulative 8 h 14CO2 exhalation in the 14C-glycocholic acid breath test. The cumulative 6 h 14CO2 exhalation in the triolein breath test was reduced in the CC group (p = 0.001) implying impaired fat absorption. There was no evidence of small-bowel bacterial overgrowth in any group. Impaired absorption of fat was related to the clinical severity of heart failure and its duration. Impaired fat absorption is associated with cardiac cachexia. It is not due to small-bowel bacterial overgrowth. The aetiology of fat malabsorption in heart failure requires further studies.

Aged↗
PubMed2005

Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1beta -511 single nucleotide polymorphism.

BACKGROUND: Cachexia is common in chronic obstructive pulmonary disease (COPD) and is thought to be linked to an enhanced systemic inflammatory response. OBJECTIVE: We investigated differences in the systemic inflammatory profile and polymorphisms in related inflammatory genes in COPD patients. DESIGN: A cross-sectional study was performed in 99 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages II-IV), who were stratified by cachexia based on fat-free mass index (FFMI; in kg/m2: <16 for men and <15 for women) and compared with healthy control subjects (HCs). Body composition was determined by bioelectrical impedance analysis. Plasma concentrations and gene polymorphisms of interleukin 1beta (IL-1beta -511), IL-6 (IL-6 -174), and the tumor necrosis factor system (TNF-alpha -308 and lymphotoxin-alpha +252) were determined. Plasma C-reactive protein, leptin, and urinary pseudouridine (as a marker of cellular protein breakdown) were measured. RESULTS: Fat mass, leptin, and pseudouridine were significantly different (P < 0.001) between noncachectic patients (NCPs) and cachectic patients (CPs: n = 35); the systemic inflammatory cytokine profile was not. NCPs had a body compositional shift toward a lower fat-free mass and a higher fat mass compared with HCs. CPs and NCPs had a greater systemic inflammatory response (P < 0.05) than did HCs, as reflected in C-reactive protein, soluble TNF-R75, and IL-6 concentrations. The overall distribution of the IL-1beta -511 polymorphism was significantly different between the groups (P < 0.05). CONCLUSIONS: In COPD patients, who are characterized by an elevated systemic inflammatory response, cachexia is not discriminatory for the extent of increase in inflammatory status. This study, however, indicates a potential influence of genetic predisposition on the cachexia process.

Adipose Tissue↗
PubMed2006

Cachexia: pathophysiology and clinical relevance.

Cachexia causes weight loss and increased mortality. It affects more than 5 million persons in the United States. Other causes of weight loss include anorexia, sarcopenia, and dehydration. The pathophysiology of cachexia is reviewed in this article. The major cause appears to be cytokine excess. Other potential mediators include testosterone and insulin-like growth factor I deficiency, excess myostatin, and excess glucocorticoids. Numerous diseases can result in cachexia, each by a slightly different mechanism. Both nutritional support and orexigenic agents play a role in the management of cachexia.

Aging↗
PubMed1990

Lipolytic factors associated with murine and human cancer cachexia.

We have identified a lipolytic factor in extracts of a cachexia-inducing murine carcinoma (MAC16) that shows characteristics of an acidic peptide and appears to be composed of three fractions of apparent molecular weights corresponding to 3 kd, 1.5 kd, and 0.7 kd, as determined by exclusion chromatography. Material with identical chromatographic and molecular weight characteristics was also present in the serum of patients with clinical cancer cachexia but absent from normal serum, even under conditions of starvation. The MAC16 lipid factor, when injected into animals bearing the non-cachexia-inducing tumor MAC13, was capable of inducing weight loss without a significant reduction in food intake. Similar lipolytic material, although in lower concentration, was also found in the MAC13 tumor extracts. These findings suggest that cachexia may arise from the enhanced expression of a lipolytic factor associated with tumor cells.

Adenocarcinoma↗
PubMed2004

Rheumatoid cachexia: metabolic abnormalities, mechanisms and interventions.

We have previously identified the phrase 'rheumatoid cachexia' to describe the loss of body cell mass (BCM) that may occur among patients with rheumatoid arthritis (RA). Specifically, rheumatoid cachexia is characterized by altered energy and protein metabolism (reduced total energy expenditure, increased resting energy expenditure and increased whole-body protein catabolism) and increased inflammatory cytokine production (interleukin-1beta and tumour necrosis factor-alpha). Patients with rheumatoid cachexia consistently have a diet that appears adequate in protein and calories (based on US Dietary Reference Intakes), but with reduced physical activity. These phenomena are similar to some of the metabolic abnormalities that occur with normal ageing, but the aetiology appears to be different in RA. This review will focus on describing the metabolic abnormalities observed in rheumatoid cachexia, identifying potential mechanisms for loss of BCM and discussing strategies for intervention.

Aging↗
PubMed2001

Muscle cachexia: current concepts of intracellular mechanisms and molecular regulation.

OBJECTIVE: To review present knowledge of intracellular mechanisms and molecular regulation of muscle cachexia. SUMMARY BACKGROUND DATA: Muscle cachexia, mainly reflecting degradation of myofibrillar proteins, is an important clinical feature in patients with severe injury, sepsis, and cancer. The catabolic response in skeletal muscle may result in muscle wasting and weakness, delaying or preventing ambulation and rehabilitation in these patients and increasing the risk for pulmonary complications. RESULTS: Muscle cachexia, induced by severe injury, sepsis, and cancer, is associated with increased gene expression and activity of the calcium/calpain- and ubiquitin/proteasome-proteolytic pathways. Calcium/calpain-regulated release of myofilaments from the sarcomere is an early, and perhaps rate-limiting, component of the catabolic response in muscle. Released myofilaments are ubiquitinated in the N-end rule pathway, regulated by the ubiquitin-conjugating enzyme E2(14k) and the ubiquitin ligase E3 alpha, and degraded by the 26S proteasome. CONCLUSIONS: An understanding of the mechanisms regulating muscle protein breakdown is important for the development of therapeutic strategies aimed at treating or preventing muscle cachexia in patients with severe injury, sepsis, cancer, and perhaps other catabolic conditions as well.

Cachexia↗
PubMed2006

Role of intestinal function in cachexia.

PURPOSE OF REVIEW: Cachexia is a prominent feature in many chronic diseases, but its pathogenesis is still not fully understood. This article reviews recent research into the role of the gut barrier in the pathogenesis of inflammation and cachexia with special emphasis on two potentially catabolic diseases: liver cirrhosis and chronic heart failure. RECENT FINDINGS: There is increasing evidence that catabolic diseases such as liver cirrhosis and chronic heart failure are associated with increased gut permeability, endotoxemia and enhanced expression of proinflammatory cytokines. In liver cirrhosis normalization of portal hypertension by insertion of a transjugular intrahepatic portosystemic stent shunt obviously causes improvement not only of gut barrier function, but also of nutritional status. SUMMARY: Although its pathogenesis is not yet completely understood, proinflammatory cytokines have been implicated in the onset and progression of cachexia. Recent data support the hypothesis that impaired gut barrier function and increased permeability further translocation of endotoxins. Increased endotoxemia might be a potent trigger of systemic inflammatory response which is involved in the pathogenesis of the cachexia syndrome. Thus, it is tempting to speculate that therapeutic strategies for the improvement of gut barrier function will concomitantly improve nutritional status.

Bacterial Translocation↗