SEARCH · Search PubMed
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.
Nine patients are reported who presented with severe weight loss of up to 13.6 kg (30 lb) as a result of chronic erosive gastritis. In many the cachexia was sufficient to prompt a search for malignancy but no other lesion was found. The importance of the radiological pursuit of this diagnosis is emphasised. Illustrative case histories are presented.
Rats bearing the Yoshida AH-130 ascites hepatoma showed an increased expression of both uncoupling protein-2 (UCP2) (two-fold) and UCP3 (three- to four-fold) in skeletal muscle (both soleus and gastrocnemius). The increase in mRNA content was associated with increased circulating concentrations of fatty acids (two-fold), triglyceride (two-fold) and cholesterol (1.9-fold). Administration of nicotinic acid to tumor-bearing rats abolishes the hyperlipidemic increase associated with tumor burden. The vitamin treatment also resulted in a decreased UCP3 gene expression in soleus muscle but not in gastrocnemius. It is concluded that circulating fatty acids may be involved in the regulation of UCP3 gene expression in aerobic muscles during experimental cancer cachexia. Since the UCP3 protein could have a role in energy expenditure, it may be suggested that hypolipidemic agents may have a beneficial role in the treatment of the cachectic syndrome.
Rats bearing the Yoshida AH-130 ascites hepatoma showed an increased expression of both uncoupling protein-2 (UCP2) (194%) and UCP3 (189%) mRNA levels in skeletal muscle 7 days after tumour inoculation. Interestingly, an even greater increase was observed in mRNA for both UCP2 (278%) and UCP3 (797%) in the pair-fed animals, suggesting that the increase in gene expression was the result of the anorexia associated with tumour burden. The results constitute the first report of UCP2 and UCP3 gene expression during cancer cachexia and agree to their possible role in the increase of energy expenditure associated with tumour growth.
Microanalytical separation techniques including capillary liquid chromatography, capillary electrophoresis and capillary electrochromatography are suitable for detection of diagnostically important changes in the metabolic profiles of biological fluids. A prototype instrument was employed to serve as an integrated platform for the analysis of urine sample from patients suffering from cancer cachexia. The instrument provides for convenient, rapid and efficient multidimensional approach towards method development which would facilitate simultaneous analysis of complex biological mixtures by the above techniques.
Laxative abuse may cause systemic and metabolic changes, but cachexia has not been reported as a predominant feature. A patient with finger clubbing and extreme wasting recovered when senna intake was stopped and nutritional care provided. A diagnosis had been made of acquired common variable hypogammaglobulinaemia with absence of circulating B lymphocytes. The immunological abnormalities were corrected after senna intake was stopped and lean body mass restored.
A rare presentation of an antrochoanal polyp is reported. A 14-year-old boy presented with obstructive sleep apnoea and subnormal growth velocity for height and weight over a 1-year period. Examination revealed a post-nasal mass which following removal was confirmed histopathologically as an antrochoanal polyp. Relief of the airway obstruction was promptly followed by catch-up growth and subsequent normal growth velocities. The possible mechanisms underlying the cachexia are explored including the possible association with the obstructive sleep apnoea.
Cachexia is a common consequence of chronic illness. The nutritional abnormalities contributing to the clinical picture are often a composite of reduced appetite, dietary factors including protein, energy and micronutrient intake, malabsorption and increased consumption or loss of nutrients. In this article, using chronic heart failure as an example, we have reviewed the potential influences of chronic disease on each of these and how they might lead to the relentless progression of wasting and the poor prognosis associated with it.
Cancer cachexia is a complex, multifactorial syndrome that results from a reduction in food intake, a variety of metabolic abnormalities (including hypermetabolism) or more often a combination of the two. Multiple mediator pathways including pro-inflammatory cytokines, neuroendocrine hormones and tumour-specific factors are involved. Therapy requires a multi-model approach that addresses both reduced food intake and metabolic change. Combination treatments such as nutritional support plus metabolic/inflammation modulation promise improved functional capacity and quality of life.
Patients with chronic liver disease exhibit a progressive loss of fat and muscle mass leading to mixed protein-energy malnutrition. The severe loss of muscle mass and body cell mass have convincingly been shown to carry a grave prognosis. Cachexia is likely to progress due to increased requirements as a consequence of hypermetabolism on the one hand and reduced volitional food intake and malabsorption on the other. Hypermetabolism may be mediated by factors such as frequent episodes of endotoxinemia, an activation of the inflammatory cytokine and/or the beta-adrenergic system. Some of these factors may also be responsible for reduced appetite. Obviously, these mechanisms may also be operative in other disease entities but clearly, portal hypertension and portosystemic shunting pose the cirrhotic patient at a particular risk for such disturbances including that of malabsorption. Apart from the established value of providing sufficient nutritious substrate to meet requirements the use of beta-adrenergic blocking agents and endotoxinemia lowering strategies seem worthwhile options that merit further clinical evaluation.
Patients with advanced lung disease (ALD) demonstrate changes in body composition characteristically manifested by a progressive loss of body weight. The mechanisms of this pulmonary cachexia syndrome are multifactorial, and treatment must be comprehensive in nature. This article addresses our current knowledge regarding the relationship between nutrition and ALD.
The implantation of the Lewis lung carcinoma (a fast-growing mouse tumour that induces cachexia) to both wild-type and gene-deficient mice for the TNF-alpha receptor type I protein (Tnfr1 degree/Tnfr1 degree), resulted in a considerable loss of carcass weight in both groups. However, while in the wild-type mice there was a loss of both fat and muscle, in the gene-knockout mice muscle wastage was not affected to the same extent. In both groups, tumour burden resulted in significant increases in circulating TNF-alpha, a cytokine which, as we have previously demonstrated, can induce protein breakdown in skeletal muscle. Muscle wastage in wild-type mice was accompanied by an increase in the fractional rate of protein degradation, while no changes were observed in protein synthesis. The result is a decreased rate of protein accumulation that accounts for the muscle weight loss observed as a result of tumour burden. In contrast, gene knockout mice did not have significantly lower rates of protein accumulation as a result of tumour implantation. The increase in protein degradation in the tumour-bearing wild mice was accompanied by an enhanced expression of both ubiquitin and proteasome subunit genes, all of them related to the activation of the ATP-dependent proteolytic system in skeletal muscle. Tumour-bearing gene-deficient mice did not show any increase in gene expression. It is concluded that TNF-alpha (alone or in combination with other cytokines) is responsible for the activation of protein breakdown in skeletal muscle of tumour-bearing mice.
OBJECTIVES: Anorexia is a major clinical problem in large number of patients with advanced cancer disease. Serotonergic mechanisms are assumed to play a role in the process of feeding behavior during normal and pathologic circumstances, which may also involve cancer anorexia according to previous experimental and clinical studies. METHODS: In the present study, we evaluated the effect of the tricyclic antidepressants desipramine (7.5 mg x kg(-1) x d(-1), intraperitoneal) and imipramine (2 to 5 mg. kg(-1) x d(-1), intraperitoneal) the serotonin synthesis inhibitor para-chlorophenylalanine (300 mg x kg(-1) x d(-1), intraperitoneal), the serotonin receptor 5-HT(2C) antagonist cyproheptadine (5 mg x kg(-1) x d(-1), intraperitoneal) and the selective serotonin reuptake inhibitor citalopram (20 mg x kg(-1) x d(-1), intraperitoneal) on anorexia in MCG-101 tumor-bearing mice, a model with significant anorexia and cachexia sensitive to cyclooxygenase inhibition. Also, MCG 101-bearing mice develop well-recognized alterations in brain tryptophan/serotonin metabolism as increased Trp, 5-HPT, and 5-HIAA during tumor progression. RESULTS: Daily provision of desipramine, imipramine, para-chloropheylalanine, cyproheptadine, and citalopram at doses that cause behavioral and metabolic alterations in normal mice did not alter food intake or body weight in tumor-bearing and healthy control mice. Also, the treatments did not decrease elevated plasma concentrations of interleukin-6 and prostaglandin E(2) in the tumor-bearing mice. CONCLUSIONS: Thus, our results do not support previous observations that serotonin metabolism itself is a major factor behind anorexia in tumor-bearing animals in general. Rather, other mechanisms, such as eicosanoid and nitric oxide-dependent pathways, seem to be more important for induction of anorexia along tumor progression in the present model.
Prevention of gut hypoplasia associated with total parenteral nutrition (TPN) was investigated in 67 adult male Fisher 344 rats. Mass and protein content of the small intestine was reduced by 31% and 39%, respectively, after 7 d of TPN in tumor-bearing (TB) rats. Coinfusing peptide YY (PYY; 1 nmol.kg-1.h-1) and treating the rats with the anabolic beta-adrenergic agonist, clenbuterol (CLE; 2 mg.kg-1.d-1), resulted in significant savings in small intestine weight (26% increase) and protein (42% increase). Although the colon also exhibited a significant decrease in mass (31%), none of the treatment combinations were effective in this region of the gut. Histologic analysis of ileum suggested that the additive effects of PYY and CLE were due to differential effects of these compounds on mucosal and muscular tissues, respectively. This combination of treatments also resulted in significant savings (30% increase) in gastrocnemius protein, suggesting a reduction in the cachectic response. These results suggest that TPN-induced gut hypoplasia and cancer cachexia may be reduced by the proper combination of nutritional, hormonal, and pharmacologic treatments. In addition, the anabolic effects of various treatments may be additive to counteract TPN-induced gut atrophy.
Tristetraprolin (TTP) is a widely expressed potential transcription factor that contains two unusual CCCH zinc fingers and is encoded by the immediate-early response gene, Zfp-36. Mice made deficient in TTP by gene targeting appeared normal at birth, but soon manifested marked medullary and extramedullary myeloid hyperplasia associated with cachexia, erosive arthritis, dermatitis, conjunctivitis, glomerular mesangial thickening, and high titers of anti-DNA and antinuclear antibodies. Myeloid progenitors from these mice showed no increase in sensitivity to growth factors. Treatment of young TTP-deficient mice with antibodies to tumor necrosis factor alpha (TNF alpha) prevented the development of essentially all aspects of the phenotype. These results indicate a role for TTP in regulating TNF alpha synthesis, secretion, turnover, or action. TTP-deficient mice may serve as useful models of the autoimmune inflammatory state resulting from chronic effective TNF alpha excess.
The present paper reviews current knowledge of the pulmonary cachexia syndrome with reference to chronic obstructive pulmonary disease (COPD). Aspects of incidence, aetiology and management are discussed. Malnutrition occurs in approximately one-quarter to one-third of patients with moderate to severe COPD. Both fat mass and fat-free mass become depleted. Loss of fat-free mass is the more important and appears to be due to a depression of protein synthesis. Weight loss is an independent prognostic indicator of mortality, and is associated with increased morbidity and decreased health-related quality of life. The aetiology of malnutrition in COPD is not well understood. Reduced food intake does not seem to be the primary cause. Resting energy expenditure (REE) is elevated in a proportion of patients and probably contributes to negative energy balance. Measurement of actual REE is helpful when considering the adequacy of nutritional supplementation. The underlying reason for a hypermetabolic state is not known. Although weight-losing COPD patients are not catabolic, nutritional supplementation alone does not appear to reverse the loss of fat-free mass. Strategies involving nutritional supplementation in combination with a second intervention are being explored, and there are some encouraging results using anabolic hormones.
BACKGROUND: The aim of the present study was to summarise evidence from scientific studies on cancer anorexia-cachexia syndrome in order to assess and highlight the efficacy of high-dose progestins (megestrol acetate and medroxyprogesterone acetate) compared with placebo in patients with hormone-independent tumors. MATERIALS AND METHODS: A systematic review of published randomised clinical trials was carried out by an extensive electronic and hand search through databases, relevant journals and books, congress, proceedings, reference lists, without any language or year of publication restriction. The research was conducted by two independent operators who collected the data in a form specifically designed for this review. Among the several possible outcomes, appetite and body weight were chosen. RESULTS: Fifteen randomised clinical trials (more than 2000 patients) were retrieved for the review. There was a statistically significant advantage for high-dose progestins as regards improved appetite: pooled odds ratio (OR) = 4.23, 95% confidence interval (CI): 2.53-7.04. Although the effect of high-dose progestins on body weight was less impressive, statistical significance was also reached for this outcome: pooled OR = 2.66, 95% CI: 1.80-3.92. Treatment morbidity was very low, due to the brief period of the treatment in most of the studies. CONCLUSIONS: The effects of high-dose progestins on appetite and body weight were clearly demonstrated. However, further studies are undoubtedly warranted to investigate other aspects of progestin activity, especially as regards dosage, duration and timing with best therapeutic index.
Free radicals play an important role in the initiation and progression of inflammatory bowel disease (IBD). Therefore, the reduction or elimination of adverse oxidant effects can provide novel therapy for IBD. Here, the antioxidant capacity and protective effects of a new class of chemically modified hetastarch (polynitroxyl starch, or PNS) plus 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol or TPL) (PNS/TPL) were assessed in a model of colitis. The superoxide scavenging capacity of PNS/TPL-that is, the inhibition of the reduction of cytochrome c in the presence of xanthine/xanthine oxidase (X/XO)-was evaluated in vitro. The effects of PNS/TPL on X/XO-induced neutrophil endothelial adhesion in vitro were investigated. Also, this study tested the protection produced by PNS/TPL in a mouse model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. PNS/TPL was given intravenously immediately before (< 30 min) and intraperitoneally at 24 and 72 hr after TNBS induction. The body weight and survival rate of the mice were checked daily. Colonic mucosal damage was assessed on the 7th day by measuring intestinal permeability to Evans blue (EB) in vivo. The ability of PNS to reoxidize bioreduced TPL was documented by whole-body electron paramagnetic resonance (EPR) detection. We found that PNS or TPL exhibits superoxide dismutase (SOD)-like activity, with approximately 2% of SOD activity occurring on a molar basis. The endothelial-neutrophil adherence induced by X/XO was significantly inhibited by PNS/TPL but not by TPL alone. PNS/TPL protected against cachexia and mortality, both usually induced by TNBS. Epithelial permeability was increased significantly in TNBS mice but was ameliorated by the administration of PNS/TPL. In conclusion, PNS/TPL may be beneficial in the treatment or prevention of IBD through its antioxidant effects, which inhibit oxidant-mediated leukocyte adhesion and injury to endothelial cells.
The Walker 256 carcinosarcoma was shown to lack the enzyme 3-ketoacid CoA transferase. This suggests that ketone bodies cannot be used as a major substrate for the energy metabolism of this tumour. Systemic ketosis (1-2 mM acetoacetate plus 3-hydroxybutyrate) was induced both in tumour-bearing and in non-tumour-bearing rats with a diet containing 70% medium chain triglyceride. However, in rats bearing the Walker 256 tumour, this dietary ketosis did not reduce the tumour growth rate nor did it prevent the subsequent decrease in host body weight. Host body nitrogen losses were similarly unaffected. The ketosis induced in tumour bearing rats was shown to be abnormal since the blood glucose concentration of ketotic, tumour-bearing rats was significantly higher compared with that of ketotic non-tumour bearing rats (5.2 +/- 0.4 mM cf 3.4 +/- 0.6 mM, P less than 0.01). These results may partly explain why systemic ketosis failed to alter the growth and cachexia induced by the Walker 256 carcinosarcoma.