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An analysis of the association of gastroenteric lesions with chronic wasting syndrome of marmosets.

Retrospective pathology data from necropsies of 162 marmosets, Saguinus oedipus, were studied to determine the nature of chronic wasting syndrome, a poorly defined entity associated with a high mortality rate in many marmoset colonies. Paraffin sections of the gastroenteric organs of 116 of these marmosets were re-examined in detail; lesions were identified, quantitated, and analyzed with a method of multiple chi-square testing for possible associations between findings. Five distinct disease entities were identified: prosthenorchosis, amebiasis, paramyxovirus disease, sepsis, and chronic colitis. Lesions of several of these often occurred in the same monkey, and all but the first were associated with cachexia. Lesions of chronic colitis were crypt abscesses, mononuclear and polymorphonuclear infiltration of the lamina propria, epithelial cell atypia, karyorrhexis, and lymphoid hyperplasia. The cause of chronic colitis was not identified, nor was any explanation found for weight loss and increased susceptibility to disease.

Animals↗

[Bacterial nosocomial infections in urology: defective wound healing].

The highest incidence of defective wound healing in all surgical disciplines is observed after urological operations. Wound infections occur in more than 8% of all urological patients. Defective wound healing appears in about 17% of unselected nephrectomy cases, rising to 50% when pyonephrosis is present. Simple adenomectomy is associated with wound infection rates of between 8 and 12% in preoperatively uninfected patients and up to 50% in patients with preoperative bacteriuria. Numerous factors may influence wound healing, e.g. age, obesity, cachexia, chronic infectious and non-infectious diseases, anaemia, thrombopathy, faulty asepsis and antisepsis, preoperative showering and shaving, skin preparation, hand degerming, skin draping, duration of hospitalization, traumatic operative technique, suture material, diathermy, timing and length of operation, duration of hospitalization, and antibiotic regimen. Strict attention has to be paid to these factors if the incidence of postoperative wound infection is to be kept within reasonable limits.

Age Factors↗

[Systemic complications of tumors].

Tumours may give rise to systemic complications, among others by the release of specific substances. The accompanying symptoms are referred to as paraneoplastic syndromes. These complications have a marked effect on the course run by the disease. A number of common syndromes which are easy to diagnose, are discussed in a survey of the literature, namely: cachexia, anorexia, fever, hypercalcaemia, hypoglycaemia, anaemia and coagulation defects. Attention is paid to the occurrence of the syndromes in man and dogs, the relationship with specific forms of tumour, the pathogenesis and some forms of possible therapy.

Anemia↗

Effect of nursing interventions on nutritional and performance status in cancer patients.

Cancer patients, assessed as nutritionally at risk, were randomly assigned to a control group or to one of four intervention groups receiving (a) nutritional supplementation, (b) relaxation training, (c) both nutritional supplementation and relaxation training, or (d) neither nutritional supplementation nor relaxation training. Fifty-five subjects completed a four-month intervention period during which they were visited biweekly by a nurse (except control subjects). In repeated measures analyses of variance, significant group-by-time interactions were obtained for weight and arm muscle circumference (a measure of protein stores), indicating that for these measures the groups changed differentially during the intervention period. The group-by-time interaction approached significance on the Karnofsky Performance Status Scale. For all three variables, gain was greatest for the relaxation group; the most severe loss occurred in the control group. These findings suggest that the cachexia of cancer may be slowed or reversed through noninvasive nursing interventions.

Activities of Daily Living↗

Influence of hydrazine sulfate on abnormal carbohydrate metabolism in cancer patients with weight loss.

Thirty-eight patients with advanced cancer and weight loss were tested in a prospectively randomized, double-blind, placebo-controlled trial to evaluate the influence of hydrazine sulfate on carbohydrate metabolism in cancer cachexia. All patients had an initial 3-day inpatient metabolic evaluation including: standard 5-hr p.o. glucose tolerance test, hormone studies, and total glucose production by infusion of [6-3H]glucose. After 30 days of treatment with capsules containing either placebo or hydrazine sulfate in a 60-mg, 3 times/day dosage, inpatient evaluation was repeated. A total of 62 metabolic inpatient evaluations were performed. The pretreatment characteristics of age, sex, prior therapy experience, nutritional parameters and tumor types were comparable in placebo and hydrazine treatment groups. On initial evaluation, abnormal glucose tolerance and increased glucose production were frequently seen. Serial assessment of glucose tolerance showed no improvement after 30 days of placebo treatment. However, the glucose tolerance was significantly improved in patients receiving 30 days of hydrazine sulfate [2-hr glucose; initial 169 +/- 24 (S.E.) mg/dl versus final 128 +/- 12 mg/dl; p less than 0.05]. In addition, the rate of total glucose production was significantly decreased after 30 days of hydrazine sulfate compared to placebo treatment (2.46 mg/kg/min versus 3.07 mg/kg/min, respectively; p less than 0.05). Toxic effects of hydrazine sulfate were minimal. Our results suggest that hydrazine sulfate can influence the abnormal carbohydrate metabolism associated with weight loss in patients with cancer.

Adult↗

Protein synthesis measured in vivo in muscle and liver of cachectic tumor-bearing mice.

Protein synthesis has been measured in vivo in liver and muscle of mice bearing the XK1 tumor, an appropriate model for cancer cachexia. Two different methods were used involving measurement of tracer incorporation into tissue protein either at the end of a 4-hr constant infusion of [14C]tyrosine or 10 min after i.v. injection of a flooding dose of [3H]phenylalanine. Whole-body tyrosine flux was decreased by 60% in cachectic tumor-bearing mice, and protein synthesis was depressed by 70% in muscle and by 40% in liver. The depression of protein synthesis in muscle was due to a reduction in both RNA content (i.e., protein-synthesizing capacity) and RNA activity (i.e., protein synthesized per g of RNA per hr). In liver, the depression of protein synthesis was due entirely to a decrease in RNA activity. The results also suggest that the synthesis of export proteins was affected more than the synthesis of fixed liver protein. Restriction of food intake in normal mice by up to 50% caused a loss of body weight and reductions in protein synthesis in liver and muscle which were less severe than those caused by the presence of the tumor. It is concluded that the wasting which is associated with advanced malignant disease is brought about by a reduction in the rate of protein synthesis in the tissues, and that this cannot be explained by depression of food intake alone.

Adenocarcinoma↗

Hyperalimentation in cancer.

A growing body of work has been addressed to the hypothesis that because patients with cancer who have poor nutritional status have a worse prognosis, increased nutritional support in these patients will result in better tolerance of surgical interventions, chemotherapy and radiation therapy, and a better outcome from the cancer. Although the hypothesis is an attractive one, there is only a single well-conducted, randomized, prospective trial to date that shows that active nutritional support is of benefit in the therapy of patients with cancer. Based on this review of the literature, it is felt that though cachexia is clearly of negative import in patients with cancer, there is little evidence to support the hypotheses that any nutritional support changes the outcome or the course of therapy of patients with cancer. It seems reasonable to continue the nutritional support to cachectic patients with cancer concomitant with specific anticancer therapy, but supportive nutritional therapy alone with postponement of specific anticancer treatment, as in awaiting weight gain or anabolism, cannot be justified with the current state of the art.

Cachexia↗

Enteral versus parenteral nutritional support in cancer patients.

There are many theoretical and practical advantages to enteral rather than parenteral administration of nutrients. However, it is unlikely that enteral supplementation of nutritional intake as presently practiced will be successful as a primary therapy for most patients with the cancer cachexia syndrome. The most likely role of enteral nutritional support (ENS) is in conjunction with other therapies. This modality deserves evaluation in surgery with curative intent. Changes in diet are effective in reducing the gastrointestinal symptoms of abdominopelvic irradiation, but the effect of ENS on the hematologic toxicity of radiation therapy and on response rates and survival is unclear. Elemental diets can reduce the gastrointestinal toxicity of conventional doses of 5-FU, but they worsen the mortality and hematologic toxicity of higher doses. Factors such as protein, fat, and carbohydrate sources, degree of hydrolysis of protein, lactose content, and timing of dietary manipulations are important in evaluating the response to ENS.

Animals↗

Energy and tissue metabolism in patients with cancer during nutritional support.

The present study evaluates the energy and skeletal muscle metabolism in malnourished patients, with and without cancer, in response to nutrition. The energy balance was positive in all patients receiving nutritional support. This led to an increase in body weight and body potassium levels. Glucose turnover increased in all patients. In patients with cancer, elevated glucose turnover reflected increased utilization of glucose preferentially for synthetic pathways rather than for oxidation. Protein synthesis and RNA content in skeletal muscles increased during nutrition. Nutritional support improved energy balance and protein synthesis capacity in skeletal muscles in patients with cancer to the same extent as in malnourished patients without cancer. Malignant cachexia seems to be a consequence of a relative lack of energy and not of impaired energy utilization in host tissues, at least early in the disease.

Aged↗

Animal models for the study of cancer-induced anorexia.

Walker carcinoma 256/B transplanted sc in CD-COBS rats induce a decrease of food intake when the tumor size is less than 5% of the body weight. This anorexia is accompanied by a decrease of the adipose tissue and, to a lesser extent, of muscular tissue. The mechanism involved in cancer-induced anorexia seems to be different from that of classic centrally acting anorectic agents. Among the drugs tested to counteract this anorexia only cyproheptadine shows a modest effect. Cyclophosphamide reduces tumor growth and prevents decrease in food intake. It is suggested that Walker carcinoma 256/B may be a useful animal model to study problems related to cancer-induced anorexia and cachexia.

Animals↗

Feeding response of tumor-bearing rats to insulin and insulin withdrawal and the contribution of autonomous tumor drain to cachectic depletion.

The Walker 256 carcinosarcoma growing in Sprague-Dawley rats and the Morris 5123 hepatoma growing in Buffalo rats both produce cachexia but have widely differing patterns of host metabolism and tumor growth. Both organisms respond to exogenous insulin with increased food intake and rate of weight gain of host. The insulin treatment response of food intake was 1.5 to 2 times and of body weight gain was 2 to 3 times that of tumor-free controls. Insulin does not accelerate tumor growth. On withdrawal of insulin, the reactive hypophagia seen in tumor-free rats does not occur in tumor bearers, and the host weight does not return to the expected untreated value as it does in tumor-free rats. Most of the weight gained during insulin treatment of tumor bearers above that gained by tumor-free rats is retained after withdrawal of insulin. A computer model based on the inference from these results, that the tumor-bearing host is blind to body weight error, indicates that this abnormality of feeding control could account for only about one-third of the observed depression of host weight and food intake.

Animals↗

Malnutrition and hypernatremic dehydration in breast-fed infants.

Despite the well-recognized advantages of breast-feeding to both mother and child, malnutrition of breast-fed infants can occur. We report two cases of breast-fed infants with cachexia, hypernatremia, and, in the one case in which it was measured, an elevated level of breast-milk sodium. These cases, along with several reported previously, emphasize the need for proper education and close and early follow-up of the nursing mother and infant, especially since a lack of parental awareness can be part of this syndrome.

Breast Feeding↗

The natural history of nonalcoholic fatty liver: a follow-up study.

Nonalcohol-induced fatty liver is widely believed to be a benign condition with little or no risk of disease progression. There have been occasional reports of progression to cirrhosis but none in the absence of preexisting fibrosis on the index biopsy specimen even when co-existing hepatitis was present (steatohepatitis). From our histological database (1978 to 1985), we identified 161 patients with fatty liver seen at our institution and traced the case notes of 156. One hundred five patients were initially excluded as having an alcohol-induced cause, and the remaining 51 either were seen in the clinic (37) or had died, in which cases copies of their death certificates were obtained (14). A further 7 patients were excluded after clinic attendance gave evidence of alcohol excess and another 4 after review of their initial biopsy showed the presence of fibrosis or steatohepatitis. The apparent cause of the steatosis in the 40 included patients with strictly nonalcohol-induced pure fatty liver was obesity in 12, diabetes in 4 (1 obese patient), and cachexia associated with extrahepatic malignancy in 6. Four of the remaining 19 had serological evidence of an autoimmune disorder, but none of these had any clinical or histological features of autoimmune liver disease. Nine patients had evidence of hyperlipidemia, 3 of whom were also obese. At a median follow-up of 11 years (7 to 16), 12 of 26 living patients had abnormal results of liver blood tests and had repeat liver biopsies performed. None had progressed to steatohepatitis or cirrhosis; 1 obese patient had developed mild fibrosis 9.8 years after her index biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Transgenic models of HIV-1.

Transgenic technology has been very successful at providing insights into possible processes involved in HIV-induced pathogenesis. The availability of these small animal models for the study of HIV-related syndromes including KS, epidermal proliferative lesions, HIV-associated nephropathy, AIDS-related growth failure and cachexia may well facilitate the development of novel therapies for these complications. Other phenotypes created in mice, such as cataracts and hepatic cancer [59], may not have human analogies but may still provide insight into pathogenesis. Thus, transgenic models have already provided resources to study many manifestations of AIDS and others are likely to be developed. The optimal strategy for designing future transgenic animals, however, is less clear. No transgenic mouse model has been generated to date that will provide an avenue for vaccine development. This advance awaits the further discovery of the host factors that facilitate the virus replicative cycle in humans and a better understanding of these pathways in the mouse. For the development of molecular-based therapy, however, the currently available models may well be adequate to test molecular inhibitors of transcription [7,60,61] and post-transcriptional processing of viral mRNA [62]. Whether single or multigenic constructs under the control of the LTR are better or worse for this purpose is a debatable issue. Transgenic technology may yet make an additional contribution to the development of molecular therapy for AIDS. The best method of demonstrating that a gene therapeutic strategy is safe to administer to patients has not been determined. By introducing potentially therapeutic constructs into mice as transgenes, their safety can be assessed in many different cell types in vivo, analogous to toxicological testing in rodents for systemically administered drugs. Thus, transgenic technology has already provided insights into the pathogenesis of HIV-1. While it has not yet proven its utility for vaccine development, transgenic technology holds the promise of being an active participant in the development of both safe and effective gene therapy approaches for the treatment of AIDS.

AIDS Dementia Complex↗

Altered insulin response to glucose in weight-losing cancer patients.

Cancer cachexia and the underlying metabolic disturbances are due in part to either altered insulin release and action. Glucose intolerance in cancer patients is frequently observed but the nature of the insulin response is not usually described. The aim of this study was to investigate the insulin response in fasted, weigh-losing cancer patients following an oral glucose load (75 g). All cancer patients (n = 35) showed glucose intolerance. Three types of response were identified; those with an increased insulin: glucose ratio (I:G) at 60 min, (average 12.3, n = 13), those with a normal I:G (average 7.2 n = 7) and those with a decrease I:G (average 4.2, n = 15). Fasting plasma glucose concentrations were normal in all groups prior to the glucose tolerance test. However, patients with the lowest I:G also had the lowest fasting plasma insulin concentrations, the lowest plasma albumin concentrations and the highest plasma triglyceride concentrations. Those patients with an abnormal insulin response (either high or low I:G) had significantly greater weight loss (16% for low I:G group, 13% for the high I:G) compared to the normal responders (8%). Plasma fatty acid concentrations were increased in all cancer patients and decreased appropriately after glucose administration, indicating that lipolysis remained sensitive to the action of insulin. It is concluded that weight loss in cancer is associated with glucose intolerance and an abnormal insulin response, and that this response is indicative of either insulin resistance (high I:G) or decreased pancreatic function (low I:G). These findings suggest a role for insulin replacement therapy in the latter group of patients.

Blood Glucose↗

[Carbohydrate and lipid metabolism in the cancer patient].

The role of nutrition in cancer patients is highly important, not just in preventing development of the cancer but also in avoiding greater weight loss accompanying the cancerous cachexia in the evolution of the cancer. The different ways of treating cancer also involve increased deterioration of the nutritional state. To design a correct nutritional strategy for these patients, it is fundamental to understand the anomalies present at the metabolic level, including those affecting the cancer carrying host and those observed in the tumor itself. The results of various studies carried out on animals and neoplastic subjects using predominantly glucose as the non-protein calorie source suggest a stimulating effect on tumor growth. On the other hand, it appears that there is, at the level of the tumor, an inability to correctly oxidize fatty acids. Enhanced knowledge of the different alterations to carbohydrate and fat metabolism found in cancer patients might aid in a better grasp and design of a nutritional strategy aimed at reducing morbidity and mortality in these patients and improving their quality of life.

Animals↗

Control of common symptoms in advanced cancer.

In common with any medical problem, careful assessment and an analytical approach are the keystones to effective symptom control in advanced cancer. When dealing with such symptoms the multi-faceted pathophysiology must be considered, and due attention paid to the affective component of pain and other symptoms. Adequate care given to history taking and a knowledge of the likely pathogenesis of symptoms in advanced cancer can prevent unnecessary investigations and fruitless trials of inappropriate symptomatic remedies. The treatment chosen should be the simplest effective regimen tailored to the individual patient. The importance of explanation to the patient cannot be overstated and is an integral part of any treatment and the sole component of many. This paper reviews the management of common symptoms in advanced cancer (dyspnoea, nausea and vomiting, constipation, anorexia-cachexia syndrome, hypercalcaemia, confusion, insomnia and depression.

Anorexia↗

[Antitumor and anticachectic activity of UFT in BALB/c mice bearing colon 26 adenocarcinoma].

We established a cancer cachexia model in BALB/c mice bearing Colon 26 and examined antitumor and anticachectic activity of UFT. The mice bearing Colon 26 showed a progressive loss of body weight, loss of lipid, and hypalbuminosis associated with the change of tumor size and these symptoms were improved by removal of cancer. In this model UFT extended life span significantly at 15mg/kg/day though showed a little growth inhibitory activity. UFT showed a significant tumor growth inhibitory activity and extended life span at 20mg/kg/day and could reverse all biological parameters mentioned above. Since the intratumor and plasma contents of IL-6 were significantly lowered in the UFT administered group, it is estimated that the anticachectic activity of UFT originates from reduction of interleukin-6 in tumor.

Adenocarcinoma↗

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