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At least 199 records · Page 11Linked to original sources
PubMed1992

Insulin-like growth factor I preserves host lean tissue mass in cancer cachexia.

Insulin-like growth factor I (IGF-I) has been implicated in the regulation and maintenance of skeletal muscle protein balance and thus may be of potential benefit in attenuating the cancer-cachectic process. To examine this hypothesis, 47 sham or tumor-implanted Fischer 344 rats were randomized to receive either continuous subcutaneous IGF-I (220 or 400 micrograms/day) or saline as control. In the tumor-bearing (TB) population, IGF-I-treated groups showed a dose-dependent increase in host weight gain (P less than 0.05), final carcass weight (P less than 0.05), and gastrocnemius muscle weights (P less than 0.05) and protein contents (0.50 +/- 0.02, 0.40 +/- 0.01, and 0.52 +/- 0.03 g/100 g host wt, for non-TB saline, TB saline, and TB 400 mg IGF-I groups, respectively; P less than 0.01, IGF-I vs. saline). Similar increases in muscle RNA and DNA contents (P less than 0.01) were induced by IGF-I treatment (P less than 0.05). IGF-I treatment in this rat sarcoma model significantly reduced the proportion of aneuploid cells in the tumor (aneuploid-to-diploid ratio: TB saline 1.1 +/- 0.2 vs. TB IGF-I 0.5 +/- 0.1; P less than 0.05). IGF-I treatment attenuated host muscle protein and lean tissue depletion without stimulation of tumor growth. The tumor aneuploid population was reduced in response to IGF-I treatment. Thus IGF-I may be a potential therapeutic agent in cancer-induced cachexia.

Analysis of Variance↗
PubMed1993

Experimental cachexia: effects of MCA sarcoma in the Fischer rat.

Temporal patterns of the cachectic effects of tumor growth and their relation to systemic levels of tumor necrosis factor (TNF) and IL-6 (interleukin-6) were examined in a rat model of experimental cancer cachexia employing the methylcholanthrene (MCA) sarcoma. Fischer 344 rats, implanted with biotelemeters for measuring temperature and activity, were implanted subdermally with tumor tissue fragments. Ad libitum-fed and pair-fed controls were sham incised. Bioassays for TNF and IL-6 were performed on serial plasma samples, obtained via jugular vein at 3- to 6-day intervals throughout the experimental period. Tumor growth induced significant anorexia, weight loss, and a decline in motor activity corresponding to an increase in mean plasma IL-6 levels, independent of reduced food intake or weight loss alone as shown in pair-fed controls. A significant lowering of body temperature then developed, followed by a two- to threefold increase in water consumption. The patterns of weight loss and temperature reduction differed in rate and degree from those seen with pair feeding.

Animals↗
PubMed1990

Metabolic response to enteral food in different phases of cancer cachexia in rats.

The resting energy expenditure (REE) and postprandial energy expenditure (PPEE) were measured using closed-circuit indirect calorimetry in Walker 256 carcinosarcoma-bearing rats. The results were compared to the appropriate controls. The PPEE measurements were performed after oral test feeding. At the beginning of the tumor growth, the REE and PPEE were similar in all groups. In the second week, the tumor-bearing rats showed increased REE and decreased PPEE. The tumor-bearing rats lost weight and became anorectic. After day 14, the REE rapidly dropped to very low values and the body weight continued to decrease. This study makes it possible to differentiate three phases of cancer cachexia: silent or preclinical, hypermetabolic and hypometabolic.

Animals↗
PubMed1992

Megestrol acetate for anorexia and cachexia.

Based on promising preliminary information obtained from uncontrolled pilot studies, several randomized, placebo-controlled, double-blind clinical trials have been launched to evaluate the effectiveness of megestrol acetate for the treatment of patients with anorexia and/or cachexia. The results of these studies have demonstrated that megestrol acetate can improve patients' appetites and promote nonfluid weight gain in some. They also suggest that megestrol acetate has antiemetic properties. Ongoing clinical trials are evaluating the dose-response relationship of megestrol acetate for these clinical problems and whether megestrol acetate will improve the survival of patients at risk for developing cancer anorexia/cachexia.

Anorexia↗
PubMed1994

Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation.

The cytokines IL-1 beta and TNF-alpha cause cachexia and hypermetabolism in animal models, but their role in human inflammation remains controversial. The relationship between in vitro cytokine production and metabolism was examined in 23 adults with RA and 23 healthy control subjects matched on age, sex, race, and weight. Body composition was measured by multicompartmental analysis of body cell mass, water, fat, and bone mass. Resting energy expenditure (REE) was measured by indirect calorimetry. Cytokine production by PBMC was measured by radioimmunoassay. Usual energy intake, physical activity, disability scores, medication use, and other confounders were also measured. Body cell mass was 13% lower (P < 0.00001), REE was 12% higher (P < 0.008), and physical activity was much lower (P < 0.001) in subjects with RA. Production of TNF-alpha was higher in RA than controls, both before and after stimulation with endotoxin (P < 0.05), while production of IL-1 beta was higher with endotoxin stimulation (P < 0.01). In multivariate analysis, cytokine production was directly associated with REE (P < 0.001) in patients but not in controls. While energy and protein intake were similar in the two groups and exceeded the Recommended Dietary Allowances, energy intake in subjects with RA was inversely associated with IL-1 beta production (P < 0.005). In this study we conclude that: loss of body cell mass is common in RA; cytokine production in RA is associated with altered energy metabolism and intake, despite a theoretically adequate diet; and TNF-alpha and IL-1 beta modulate energy metabolism and body composition in RA.

Adult↗
PubMedDate not supplied

Influence of total parenteral nutrition on tumor growth and polyamine biosynthesis of fibrosarcoma-bearing rats after induced cachexia.

The effect of a protein-free diet (PF) or a restricted intake of chow (RI) and subsequent host repletion with total parenteral nutrition (PF-TPN, RI-TPN) on tumor growth and polyamine metabolism of fibrosarcoma-bearing rats was examined. Host weight was significantly reduced by PF and RI. Tumor growth was reduced in malnourished rats with the PF regimen resulting in the greatest decrease. Rats receiving TPN after 14 days of the RI or PF regimens had higher host weight and plasma albumin levels than malnourished rats. Tumor growth during TPN was evaluated as the percent increase and compared with that of the respective malnourished rats. The percent increase for RI-TPN rats was significantly greater although a trend toward an increase was also evident for PF-TPN rats. Tumor ornithine decarboxylase (ODC) activity and putrescine levels were increased for PF rats and decreased for RI rats while tumor ODC activity was consistently increased by TPN. Tumor growth, ODC activity, and putrescine levels were simultaneously increased only for those rats fed the RI regimen prior to TPN. These results show a disparity in tumor ODC activity, putrescine levels, and tumor growth in malnourished rats. The results of this study suggest that the nutritional origin of cachexia influences the response of the tumor to TPN and emphasizes the importance of considering the methods to induce malnutrition in designing therapuetic regimens.

Animals↗
PubMed1991

Chinese hamster ovarian cells transfected with the murine interleukin-6 gene cause hypercalcemia as well as cachexia, leukocytosis and thrombocytosis in tumor-bearing nude mice.

The effects of interleukin-6 (IL-6) in vivo were assessed by inoculating Chinese hamster ovarian (CHO) cells which were transfected with the murine IL-6 gene in nude mice. Nude mice bearing CHO cells expressing IL-6 developed hypercalcemia. Tumor-bearing mice also showed increases in white cell count, platelet count, and decreases in body weight. In nude mice carrying CHO tumors which had not been transfected with the IL-6 gene, there were no changes in these parameters. These results suggest that increased circulating concentrations of IL-6 in patients with malignant disease may contribute to a number of paraneoplastic syndromes including hypercalcemia, cachexia, leukocytosis and thrombocytosis.

Animals↗
PubMed1975

Lateral hypothalamic demyelination and cachexia in a case of "malignant" multiple sclerosis.

A 41-year old woman had profound weight loss and cachexia as a manifestation of rapidly fatal multiple sclerosis. Demyelinating lesions were present in the lateral hypothalamus. Data from animal experiments have indicated that lateral hypothalamic lesions cause a weight loss associated with a lowering of the regulation level or "set-point" for body weight. This case suggests, therefore, that a rapid decline in the level of maintained body weight in a patient without pituitary disease or general organic disorder, or distinct emotional disorder, may represent a clinical manifestation of tissue injury of the lateral hypothalamus.

Adult↗
PubMed1994

Case report: cachexia of the kidney--a cause of pseudo-hydronephrosis.

Various pitfalls in diagnosing early hydronephrosis on ultrasound (US) have been recognized. We present a case where the appearances on US mimicked bilateral hydronephrosis in a patient undergoing treatment for recurrent colonic carcinoma. Comparison with a previous ultrasound examination demonstrated marked loss of renal sinus fat. Doppler studies demonstrated normal venous flow within each portion of the "dilated collecting system". In oncology, renal cachexia should be remembered as one of the causes of pseudo-hydronephrosis.

Cachexia↗
PubMed1994

Surgical treatment of patients with cardiac cachexia. An analysis of factors affecting operative mortality.

During the period from 1982 to 1990, we operated on 25 patients with cardiac cachexia associated with a long history of combined mitral and tricuspid diseases. The age distribution was 44 to 68 years, with an average of 58 years. The overall operative mortality was 28 percent (7/25). However, the operative mortality differed according to various factors. Patients with preoperative nutritional support had a mortality rate of 17 percent, as compared with 57 percent for those without nutritional support (p < 0.05). The operative mortality was higher in patients with giant left atrium (39 percent vs 0 percent, p < 0.01). The postoperative cardiothoracic ratio in chest radiographs was significantly decreased by left atrial plication (91.6 percent vs 74.1 percent, p < 0.05). However, the operative mortality in patients with plication was still higher than in patients whose left atrium was left intact (67 percent vs 16 percent, p < 0.025). Advanced age, female sex, advanced tricuspid regurgitation, preoperative renal failure (serum urea nitrogen > 30 mg/dl), and hepatic failure (ascites or serum total bilirubin > 2.5 mg/dl) had no significant effects on operative mortality. The results demonstrated that preoperative nutritional support resulted in significant decreases in the incidence of postoperative respiratory failure and operative mortality. In contrast, postoperative respiratory failure occurred in a high percentage of patients without nutritional support even though left atrial plication was successfully performed.

Adult↗
PubMed1992

Cancer-associated anorexia and cachexia. Implications for drug therapy.

Anorexia and cachexia are major problems in patients with cancer. Such measures as anti-cancer therapy, dietary counselling or hyperalimentation are not very successful in reversing this phenomenon in the vast majority of cancer patients. Thus, several drugs have been evaluated as agents to ameliorate cancer-associated anorexia/cachexia. Cyproheptadine is an antiserotonergic drug which appears to cause slight appetite stimulation in patients. A randomised clinical trial, however, was unable to demonstrate any weight gain from this agent. Corticosteroids are frequently used in clinical practice for appetite stimulation in patients with advanced malignancies. Supporting this practice, 4 randomised clinical trials showed that corticosteroid medications can stimulate the appetites of advanced cancer patients. However, these studies were not able to show any substantial nonfluid weight gain in treated patients. Megestrol acetate is a progestational agent which appears to be a relatively potent appetite stimulant. Randomised studies in advanced cancer patients have shown both substantial appetite stimulation and improvement in the nonfluid bodyweights of patients receiving this drug. Preliminary evidence also suggests that this drug has antiemetic properties. Several clinical studies are currently ongoing to determine the effect of various doses of megestrol acetate in patients with cancer. Efforts are also ongoing to evaluate both anabolic steroids and hydrazine sulfate as drugs for the treatment of patients with cancer anorexia/cachexia. The preliminary nature of these investigations, however, precludes recommendations for the use of either of these latter 2 drugs in routine clinical practice.

Anorexia↗
PubMed1992

Visceral leishmaniasis: a model for infection-induced cachexia.

Parasitic infections and malnutrition coexist in many tropical and subtropical areas. Studies of Leishmania donovani and of experimentally infected Syrian hamsters have provided important insights into the complex interrelationships between malnutrition and this parasitic disease. Malnutrition, which adversely affects cell-mediated immunity, is associated with the development of visceral leishmaniasis (kala-azar) in children living in endemic areas. In turn, L. donovani can cause wasting as well as hepatosplenomegaly, fever, and anemia. Syrian hamsters infected with L. donovani develop a disease that is comparable to that of humans with kala-azar. Weight loss in infected hamsters is associated with splenic macrophage secretion of potentially catabolic cytokines as measured by the D10.G4.1 assay for interleukin-1 and the L929 cytotoxicity assay for tumor necrosis factor/cachectin. Although decreased food intake contributes to wasting in infected hamsters, studies of skeletal muscle function indicate that it is not the sole factor. Leishmania donovani-infected hamsters have also been used to study drugs with the potential to prevent or reverse cachexia.

Adipose Tissue↗
PubMed1994

Megestrol acetate in patients with AIDS and cachexia.

OBJECTIVE: To study the effects of a megestrol acetate liquid formulation (800 mg/d) on body weight, body composition, caloric intake, and mental outlook in patients with the acquired immunodeficiency syndrome (AIDS) who had cachexia. DESIGN: Twelve-week, multicenter, randomized, double-blind, placebo-controlled trial. SETTING: Multiple clinical centers. PATIENTS: 100 patients with AIDS who had weight loss of 10% or more of ideal body weight were randomly assigned to placebo (n = 48) or megestrol acetate (n = 52). MEASUREMENTS: Caloric intake, body weight, body composition, and sense of well-being. RESULTS: Most patients receiving megestrol acetate had increased caloric intake resulting in body weight gain (mainly fat mass). From baseline to week 8, the megestrol acetate group increased their daily caloric intake by 608 calories, whereas the placebo group increased intake by 134 calories (difference, 474 calories; 95% CI, -68 to 880 calories). Body weight in the megestrol acetate group increased by 3.86 kg from baseline to week 8, although it decreased by 0.46 kg in the placebo group (difference, 4.32 kg; CI, 2.42 to 6.22 kg). At week 8 in the megestrol acetate group, patients gained 3.68 kg in fat mass and those in the placebo group lost 0.28 kg (difference, 3.96 kg; CI, 2.49 to 5.43 kg). Body water, lean mass, and patient survival were not statistically different between treatment groups. Patients treated with megestrol acetate had an increased sense of well-being when compared with patients who received placebo. CONCLUSIONS: This megestrol acetate liquid formulation is well tolerated, increases food intake, results in body weight gain, and improves the sense of well-being in cachectic patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1975

[Pathogenesis of cachexia in cardiac insufficiency].

In 81 patients with circulatory insufficiency of the IIB-III stage some in dices of the lipids and protein metabolism along with the blood sugar level were studied. Changes in the lipids metabolism values are more pronounced in patients with mitral defects than in those with atherosclerotic cardiosclerosis. The authors attach definite importance to these derangements in the pathogenesis of cardiac cachexia secondary to the developing circulatory insufficiency.

Adult↗
PubMed1991

Nutritional support and cancer cachexia. Evolving concepts of mechanisms and adjunctive therapies.

Despite the widespread employment of intravenous feeding in patients with cancer cachexia to improve outcome, conflicting data exist regarding the efficacy of such therapy in addressing metabolic alterations secondary to immobility, malnutrition, and disease-specific processes. Persistence of distinct abnormalities of body and tissue integrity and peripheral tissue plasma inter-organ nitrogen flux imply the need for anabolic agents to enhance the therapeutic effects of parenteral nutrition. This article focuses upon potential anabolic agents such as chronic submaximal exercise, hormonal augmentation, pharmacologic intervention, and variations in substrate composition. Finally, the immunologic, metabolic, and endocrine consequences of bypassing the gastrointestinal tract are considered and related to the limited efficacy of current total parenteral nutrition regimens.

Cachexia↗
PubMed1991

Megestrol acetate in cancer cachexia.

This randomized, controlled trial assessed the activity, tolerance, and degree of weight gain and anorexia of two doses of megestrol acetate in patients with advanced cancer and cachexia. Patients received either 480 mg/d or 960 mg/d megestrol acetate or placebo for 8 weeks. As of June 1990, 55 patients had been randomized; 16 died during the 8-week study, and it was too early to evaluate another 5 patients. The remaining 34 patients were included in analyses. The median initial weight loss ranged from 15% to 22% of usual body weight, which shows the severe degree of malnutrition. Further weight loss was seen in 6 of 8 patients in the placebo group compared with only 5 of 15 and 3 of 11 patients in the low-dose and high-dose megestrol acetate groups, respectively. The median further weight loss was comparable in all groups. Six of 15 and 6 of 11 patients in the low-dose and high-dose groups, respectively, gained weight with a median of 3 kg and 4 kg, respectively. A trend showed beneficial effects of megestrol acetate. Appetite improvement was similar in all groups. Due to the small sample size, however, there were no statistically significant differences among the three groups. Side effects of megestrol acetate were mild. In a subgroup of 15 patients, measurement of body water content indicated a decrease of body fat after 8 weeks in the placebo and low-dose groups. Only the high-dose megestrol acetate group showed an increase in both fat and lean body mass, suggesting a positive effect.

Adult↗
PubMedDate not supplied

Nutritional assessment in cancer cachexia.

Cancer cachexia causes nutritional depletion due to the tumor burden and the patient's inability to eat. A nutritional assessment is valuable in assisting the medical team in nutritionally repleting malnourished patients. Using readily available information, the practitioner can determine nutritional assessment and plan interventions that help the child to successfully withstand cancer and its treatment.

Adolescent↗