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PubMedDate not supplied

Resting metabolic rate of esophageal carcinoma patients: a model for energy expenditure measurement in a homogenous cancer population.

In cancer patients controversy exists as to the nature of changes in resting metabolic rate (RMR) and their contribution to cachexia. This study describes the fasting indirect calorimetry, and nutritional measurements made on a homogeneous group of Black patients with carcinoma of the esophagus. It compares them with a reference group. All cancer patients had localized disease and were markedly malnourished. They were on average 20 to 25% lighter than reference subjects. In the cancer patients, the triceps skinfold thickness (TSF) in mm and the hand grip strength in kg/m2, mean and SD, were, respectively, 7.3 +/- 2.8 and 28 +/- 6 for men and 12 +/- 5 and 22 +/- 3.5 for women, and were significantly lower than those of the reference subjects. Fat-free mass was calculated from the TSF measurements. In men with cancer RMR (6.06 MJ/day +/- 0.56) was significantly lower than the reference subjects values (7.07 MJ/day +/- 0.64) p = 0.002. In women with cancer RMR was on average 2 MJ/day less than in controls but this difference failed to reach significance. However, when expressed per kg fat free mass, or per kg body weight this difference is no longer apparent the RMR being 0.14 MJ/kg/fat free mass in both groups. Our interpretation is that there is no direct effect of the tumour on RMR and that energy expenditure changes are secondary to body composition changes.

Black or African American↗
PubMedDate not supplied

Dietary intake in patients with acquired immunodeficiency syndrome (AIDS), patients with AIDS-related complex, and serologically positive human immunodeficiency virus patients: correlations with nutritional status.

One of the major clinical manifestations of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) is the development of cachexia. This most likely results from a multifactorial interplay of poor diet, malabsorption, and altered metabolism. To assess the potential role of nutrient intake in the development or persistence of malnutrition, a detailed analysis was performed of a 72-hr diet record in clinically stable patients with AIDS (N = 18), ARC (N = 12) and in human immunodeficiency virus (HIV) seropositive controls without significant manifestations of disease (N = 13). Total calorie intake was 39.1 +/- 13.2 kcal/kg/day in AIDS patients vs 34.6 +/- 7.8 kcal/kg/day in ARC patients or 31.9 +/- 17.7 kcal/kg/day in HIV seropositive cases (all p = NS). Likewise, mean protein intakes were similar among the groups and exceeded recommended daily dietary allowance (RDA) guidelines. The mean body weight changes from the inception of illness were -11 +/- 1% in AIDS, -6 +/- 7% in ARC, vs +3 +/- 2% in HIV-seropositive-only cases (p less than 0.05 vs AIDS and ARC). Dietary vitamin and mineral analysis revealed that 88% of AIDS, 88% of HIV seropositive, and 89% of ARC patients were ingesting less than 50% RDA for at least one nutrient. The mean number of deficiencies per patient was 1.8 +/- 1.3 in AIDS, 3.8 +/- 3.5 in ARC, and 2.9 +/- 2.5 in HIV-seropositive-only cases (p less than 0.05 AIDS vs ARC). There were no significant correlations between specific anthropometric measurements and dietary intakes of protein or fat.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗
PubMedDate not supplied

Parenteral vs enteral nutrition in tumor-bearing rats.

The development of cachexia may complicate cancer therapy, yet controversy exists concerning its nutritional management. For example, use of total parenteral nutrition (TPN) may not be appropriate because of gut atrophy, possible stimulation of tumor growth, and lack of total host protein repletion. In the present experiment, host and tumor responses were compared after identical parenteral or enteral nutritional supplementation (EN). Eighteen days after subcutaneous inoculation of adult male Fischer-344 rats with fresh methylcholanthrene-induced sarcoma (tumor-bearing [TB] rats), catheters were placed into either the external jugular vein or the stomach. Four days later, rats were started on an 11-day course of either TPN or EN with a Freamine-III-based formula (amino acids = 6%, dextrose = 21.5%, lipid = 1.5%). When the rats were killed, there was no difference in tumor weight between the various TB groups. Carcass weight was increased significantly in both the TB-TPN and TB-EN groups, and there was an elevation in gastrocnemius protein content in both groups compared with the TB-rat food group. Small intestine protein was preserved in the TB-EN group to the level observed in the control-rat food animals. Total lipids in the liver were increased in both TB-TPN and TB-EN groups; however, the magnitude of the increase was less in the TB-EN animals. Neither treatment resulted in complete protein repletion of tumor-bearing rats. EN may be more appropriate than TPN in that gut mass is preserved. The maintenance of gut mucosa may prove to be beneficial in the treatment of the depleted, immunocompromised, and metabolically stressed host.

Animals↗
PubMedDate not supplied

Insulin resistance and the alterations of glucose transporter-4 in adipose cells from cachectic tumor-bearing rats.

BACKGROUND: Insulin resistance may play an important role in cancer cachexia; however, its mechanisms remain to be clarified. METHODS: Cellular mechanisms of insulin resistance in tumor-bearing rats (TBR) were investigated in isolated adipose cells by measuring 3-O-[14C]methyl glucose transport activity and glucose transporter-4 (GLUT4) protein in low-density microsomes at a basal state and in the plasma membrane at an insulin-stimulated state. RESULTS: The insulin-stimulated glucose transport activity in adipose cells from TBR was significantly lower than that of control rats (CTR) (0.51 +/- 0.25 and 2.27 +/- 0.11 fmol/cell/min, respectively). The amount of GLUT4 in low-density microsomes at a basal state and in plasma membrane at an insulin-stimulated state was less in TBR than in CTR. CONCLUSIONS: These data suggest that the insulin resistance seen in the adipose cells of these tumor-bearing rats was caused in part by both a decreased amount of GLUT4 protein in a basal state and a decreased translocation of GLUT4 in response to insulin stimulation.

Adipocytes↗
PubMedDate not supplied

Thalidomide: dual benefits in palliative medicine and oncology.

Thalidomide is an immunomodulator, anti-angiogenic agent, anti-cytokine, and anti-integrin. Alone or in combination with other drugs, thalidomide has also demonstrated anti-cachexin and anti-neoplastic properties. Anorexia and cachexia are common symptoms of advanced cancer. Since certain cytokines also promote tumor growth, we may have a class of agents with palliative and anti-tumor benefits in combination with anti-neoplastics and anti-cytokines, such as thalidomide.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Assessment of nutritional status and fluid deficits in advanced cancer.

Malnutrition and cachexia are frequent manifestations of cancer and are major contributors to morbidity and mortality. The assessment of nutrition status in cancer patients can be easily accomplished. The first step is to record a complete medical history and to perform a thorough clinical examination to uncover signs of nutritional deficiency. Simple and inexpensive tests are available to assess the body composition, such as: anthropometric measurements, skinfold thickness, arm muscle circumference and area, and weight and body mass index (BMI). Biochemical measurements are also available, such as serum albumin, transferring, and prealbumin. Fluid deficit is divided into two categories based on pathophysiology (dehydration and volume depletion) and to three subtypes based on plasma sodium concentration (hyponatremic, hypernatremic, and isotonic). Dehydration (total water deficit, especially intracellular) is always hypernatremic, while volume depletion (intravascular water and sodium deficit) is either hyponatremic, hypernatremic, or isotonic. There are no clear clinical differences among the various categories, but a delay of capillary refill, tachycardia, and orthostatic hypotension is more common with volume depletion. Careful clinical assessment and laboratory tests, especially serum sodium, are the keystones for diagnosis and effective management. Bioelectrical impedance (BEI) is an easy way to assess both nutrition status and fluid deficits in advanced cancer and should be used more often than it currently is. This article reviews the subjective and objective methods of assessing fluid deficit and nutrition in advanced cancer.

Biomarkers↗
PubMed1996

Hyperglycemia induced by megestrol acetate in a patient with AIDS.

OBJECTIVE: To report a case of hyperglycemia induced by megestrol acetate in a patient with AIDS. CASE SUMMARY: A 28-year-old man with AIDS developed hyperglycemia requiring insulin therapy 5 days after beginning megestrol therapy. The hyperglycemia resolved with discontinuation of the agent and treatment with insulin, and recurred 2 years later, when megestrol acetate treatment was rechallenged. In this case the patient had developed hyperglycemia and pancreatitis 1 year before, related to pentamidine therapy. DISCUSSION: To our knowledge this is the first reported case of hyperglycemia that was induced by megestrol acetate as early as 5 days after beginning therapy and confirmed by rechallenge. The mechanism of action is unclear. CONCLUSIONS: Clinicians caring for patients with AIDS-related cachexia should be aware that megestrol acetate can cause a severe but reversible hyperglycemic state.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Cancer-induced fatigue and skeletal muscle wasting: the role of exercise.

Fatigue is the most frequently reported symptom by cancer patients. Many of these patients perceive fatigue as the most distressing symptom associated with their illness because it imposes limitations on their physical activity level. Skeletal muscle wasting, which occurs as part of cancer cachexia, is one of the mechanisms that contribute to fatigue. Cancer-induced skeletal muscle wasting may occur despite normal food intake and is not prevented by nutritional supplementation. Evidence suggests that endurance exercise ameliorates cancer-related fatigue. There is no compelling evidence to support that exercise-induced reduction in fatigue is related to preservation of muscle mass. Resistance exercise attenuates muscle wasting associated with a variety of catabolic conditions. However, its effects on cancer-induced muscle wasting have not been adequately studied. This article describes the physiological mechanisms implicated in the induction of cancer-related muscle wasting, summarizes findings from endurance and resistance exercise studies in relation to fatigue and muscle wasting during cancer and selected clinical conditions, and proposes directions for future research.

Animals↗
PubMed2004

Role of omega-3 fatty acid supplementation in inflammation and malignancy.

Omega-3 fatty acids (FAs), which include eicosapentaenoic acid (EPA) and docosahexaenoic acid, are found in fish oils and have long been investigated as components of therapy for various disease states. Population studies initially revealed the cardioprotective and anti-inflammatory effects of omega-3 FAs and EPA, with subsequent clinical studies supporting the therapeutic role of omega-3 FAs in cardiovascular and chronic inflammatory conditions. Prospective randomized placebo-controlled trials have also demonstrated the utility of omega-3 FA supplementation in malignancy and cancer cachexia. In recent years, in vitro and animal studies have elucidated some of the mechanistic explanations underlying the wide range of biological effects produced by omega-3 FAs and EPA, including their antiproliferative and anticachectic actions in malignancy. In this review, the authors discuss the recent progress made with omega-3 FAs, focusing on the advances in mechanistic understanding and the results of clinical trials.

Animals↗
PubMedDate not supplied

Diffuse malignant pleural mesothelioma: Part II. Symptom management.

Patients with diffuse malignant pleural mesothelioma (DMPM) experience multiple symptoms from their disease and treatment, which can affect all aspects of their lives. Dyspnea, cough, pain, fatigue, depression, weight loss, anorexia, and cachexia are the most common symptoms. Early, ongoing assessment and management of these symptoms are imperative to maximize quality of life for patients with DMPM.

Algorithms↗
PubMed1993

Body-composition changes in patients who gain weight while receiving megestrol acetate.

PURPOSE: Randomized placebo-controlled clinical trials have now established that megestrol acetate causes appetite stimulation and weight gain in patients with anorexia and/or cachexia. There is a paucity of available data to delineate the substance of this increased weight. PATIENTS AND METHODS: Using dual-energy x-ray absorptiometry and tritiated body water methodologies, we performed body-composition measurements in 12 patients with advanced cancer before the institution of oral megestrol acetate (800 mg/d) and at subsequent 2-month intervals. RESULTS: Seven of the 12 patients gained weight (2.1 to 16.5 kg) and had repeat body-composition measurements performed at the time of maximum weight gain. The vast majority of the gained weight was clearly from an increase in adipose tissue, while there was a suggestion that an increase in body fluid was responsible for a minority of the weight gain. CONCLUSION: Megestrol acetate-induced weight gain is primarily the result of an increase in body mass.

Anorexia↗
PubMed2001

Ovarian pathology and high incidence of sex cord tumors in follitropin receptor knockout (FORKO) mice.

In this investigation we describe our observations of the status of the aging ovary in mice with disruption of the receptor for FSH. Knockout mice at 3-5 months of age are acyclic and sterile, with very small, underdeveloped ovaries. Thus, they exhibit hypergonadotropic-hypogonadism with high levels of circulating FSH similar to the postmenopausal state in women. By 12 months more than 92% of these animals developed various kinds of ovarian pathology, including neoplasms of sex cord-stromal type as well as cysts. Interestingly, the majority of tumors were located in the right ovary, with the contralateral ovary remaining unaffected but atrophic. The ovary from heterozygotes also showed pathology after 15 months. None of the age-matched wild-type mice that remained fertile developed any sign of ovarian tumors. Circulating LH and FSH levels were increased in follitropin receptor knockout mice and remained severalfold higher in tumor-bearing animals. The histological appearances of ovarian tumors were similar to the pathology observed in some types of sex cord-stromal neoplasms in women. The tumor burden caused weight loss and cachexia in follitropin receptor knockout mice. Based on these characteristics as well as the high incidence of ovarian pathology in the aging mutant, we propose that the loss of the FSH receptor signaling mechanisms predispose the ovary to molecular and structural changes leading to tumor formation. Hence, in the intact and fertile animal, FSH receptor signaling offers a protective mechanism that is lost upon reproductive senescence (menopause in women). Further studies are warranted in this genetic model to explore the molecular changes underlying the development of ovarian neoplasia.

Animals↗
PubMed2004

Interrelationship of growth differentiation factor 9 and inhibin in early folliculogenesis and ovarian tumorigenesis in mice.

To investigate the interrelationship of inhibin alpha and growth differentiation factor 9 (GDF9) during early folliculogenesis, we generated mice lacking both inhibin alpha and GDF9. Our findings on these Inha Gdf9 double-mutant mice are as follows: 1). females develop ovarian tumors and a cachexia-like wasting syndrome, resembling mice lacking inhibin alpha alone. This indicates that the granulosa cells are competent to proliferate despite the lack of GDF9; 2). follicular development progresses to multiple-layer follicle stages before tumorigenesis. This demonstrates that the up-regulation of inhibin alpha in the Gdf9 knockout ovary directly prevents the proliferation of the granulosa cells at the primary follicle stage, an effect that is released in the absence of inhibin alpha; 3). a morphological theca forms around the preantral follicles with no detectable selective theca markers [i.e. 17alpha-hydroxylase (Cyp17), LH receptor (Lhr), and Kit]. These results indicate that the theca recruitment can occur independently of GDF9, but the differentiation of thecal cells is blocked; and 4). inhibin/activin subunits betaA, betaB, and Kit ligand (Kitl) mRNA are highly up-regulated, suggesting that the increased activins and KITL play functional roles in early folliculogenesis. Thus, GDF9 appears to function indirectly to regulate early granulosa cell proliferation and theca recruitment in vivo.

Activins↗
PubMed1984

Surgical implications of the pathophysiology of advanced valvular heart disease.

The pathophysiology of advanced valvular heart disease and its clinical implications were analyzed. The study was undertaken primarily on 153 recent patients with implantation of central flow valves. The operative mortality rate was 3.9%, with deaths except one related to LOS. There was a higher incidence of LOS in left ventricular volume-overloaded hearts, and a much higher incidence in patients associated with TR: 70% of TR cases with RVEDP higher than 15 mmHg developed LOS. Cardiac contractile reserve proved to be useful index for predicting immediate postoperative and long-term results; less favorable results were indicated in patients with PWE below 10 mm even after epinephrine infusion. In volume-overloaded hearts, the muscle cell diameter of the left ventricle increased proportionally to the dimension of the left ventricle, with interstitial fibrosis representing irreversible morphological change. Patients with a prolonged indocyanine green disappearance rate showed fibrosis of the liver and were complicated more frequently by LOS, hepatic and renal disturbance and increased mortality. Patients with cardiac cachexia were liable to develop LOS postoperatively, and preoperative GIK therapy appeared to be effective in improving depressed metabolism and hemodynamics, except in patients with severe TR.

Adult↗
PubMedDate not supplied

Nursing management of nutrition in cancer and palliative care.

Malnutrition is prevalent in patients with cancer. This can have deleterious effects including reduced response to treatment, diminished quality of life, increased length of hospital stay and decreased survival. It is, therefore, imperative that thorough nutritional screening is carried out by nurses on patients' admission and during their hospital stay to detect those who are malnourished or at risk of malnutrition in order to plan their nutritional care effectively. Cancer cachexia is the progressive weight loss and emaciation seen in cancer patients, particularly in advanced disease, which can have a devastating effect on the physical, psychological, social and spiritual aspects of the patient's life. Therefore, the aims of nutritional care are identified depending on the stage of the patient's illness and recommendations made for nursing, pharmacological and nutritional intervention. These include nursing comfort strategies, the use of recommended pharmacological agents and dietary interventions such as experimenting with different foods, textures, portion sizes and nutritional supplements. The use of fish oil-enhanced nutritional supplements and artificial nutritional support is also discussed. Consideration is also given to the legal and ethical aspects of providing nutrition and nutritional support.

Appetite Stimulants↗
PubMed2003

Mechanisms underlying cancer-induced symptoms.

In addition to the physical and emotional suffering induced by the diagnosis of cancer, patients are subjected to additional discomfort and suffering from symptoms induced by both the disease and its treatment. While an increasing amount of clinical and basic science research has focused on these issues, our understanding of the mechanisms underlying cancer-related symptoms remains incomplete. This article summarizes what is known about the mechanisms underlying the common symptoms of pain, cachexia, nausea and vomiting, dyspnea, fatigue and mood disorders, as well as the implications of these findings for therapeutic intervention.

Antineoplastic Agents↗
PubMed2004

The promise of thalidomide: evolving indications.

Thalidomide was first used in the late 1950s but it was withdrawn from the market in the 1960s for its notorious teratogenic effects. This drug was more recently rediscovered as a powerful immunomodulatory and antiinflammatory agent and was approved by the FDA in 1998 for treatment of erythema nodosum leprosum. Thalidomide has shown great promise in advanced or refractory multiple myeloma either alone or in combination with other agents. It has also demonstrated benefits in a wide variety of disparate conditions such as aphthous and genital ulcers, cancer cachexia, HIV, tuberculosis and chronic graft versus host disease. Thalidomide is being investigated for treatment of renal cell carcinoma, and liver and thyroid cancers. Better understanding of its many mechanisms of action has provoked great interest in its potential use for treatment of various disorders. This review focuses on thalidomide's mechanisms of action, biochemistry, pharmacokinetics and its use in erythema nodosum leprosum as well as multiple myeloma, graft versus host disease, and renal cell carcinoma.

Cachexia↗
PubMed2002

Systemic effects in COPD.

The pathogenesis and clinical manifestations of COPD are not restricted to pulmonary inflammation and structural remodeling. Rather, this disorder is associated with clinically significant systemic alterations in biochemistry and organ function. The systemic aspects of COPD include oxidative stress and altered circulating levels of inflammatory mediators and acute-phase proteins. Indeed, an impaired endogenous oxidant-antioxidant balance has been reported in patients experiencing exacerbations of COPD, and others have observed altered circulating levels of several cytokines and adhesion molecules in patients with stable disease. As in other chronic inflammatory conditions, weight loss, muscle wasting, and tissue depletion are commonly seen in COPD patients. Selective wasting of fat-free mass coupled with impaired respiratory and peripheral muscle function and a reduced capacity for exercise occur in COPD patients. Indeed, weight loss may directly impact poor prognosis in COPD patients. The mechanisms underlying weight loss and muscle wasting are incompletely understood but likely involve an imbalance in ongoing processes of protein degradation and replacement. This may include alterations in the relative levels or activities of endocrine hormones such as insulin, growth hormone, testosterone, and glucocorticoids. Furthermore, chronic systemic inflammation involving cytokines such as interleukin-1 and tumor necrosis factor-alpha may be associated with these hormonal changes and muscle wasting in COPD patients. This review includes a discussion of the mechanisms of skeletal muscle fiber protein metabolism/catabolism, the potential roles of endogenous cytokines in protein loss, and the possibility that novel drugs that inhibit cytokine signaling may provide benefits by reducing muscle wasting and cachexia, thereby improving the prognosis and quality of life among COPD patients.

Body Mass Index↗