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At least 1,621 records · Page 90Linked to original sources
PubMed2000

Nutrition in cancer: an overview.

OBJECTIVES: To provide a review of weight loss, cachexia (both primary and secondary), and weight gain in cancer patients. DATA SOURCES: Research reports, review articles, textbooks, and personal communications. CONCLUSIONS: Alterations in nutritional status have the potential to affect mortality, morbidity, and quality of life outcomes. The detection and treatment of malnutrition is important to success of therapy. IMPLICATIONS FOR NURSING PRACTICE: Nursing interventions to help maintain optimal nutritional status in patients with cancer include careful assessment, identification of patients at risk, and management of problems before the initiation of therapy.

Cachexia↗
PubMed2000

Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases.

Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L-carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L-carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L-carnitine on the intramuscular GSH levels in cancer patients.

Adult↗
PubMed2000

Day-night pattern of energy expenditure and body temperature in cachectic tumour-bearing rats.

The implication of an increase in energy expenditure in cancer cachexia, which seems to be related to the type of tumour, remains unclear. We therefore investigated the energy metabolism and body temperature in anorectic and cachectic rats bearing the Yoshida sarcoma (TB), in comparison with pair-fed (PF) and ad-libitum fed (AL) control rats. The resting energy expenditure was higher in the TB than in the two control groups when corrected for the modifications of body composition. However, the total energy expenditure did not differ between the TB and the AL, presumably because of the drop of activity in TB. There was a temporal distribution of differences in energy expenditure with higher energy expenditure in TB than in AL during the diurnal phase and a lack of difference during the nocturnal phase. The TB presented a fever, which was limited to the diurnal period. Moreover, the acrophase of the body temperature rhythm was delayed in the TB. These results highlight the circadian effects of tumour development on the energy metabolism of the host and hint to the possible implication of cytokines.

Adipose Tissue↗
PubMed2000

Comparative analysis of mycobacterial infections in susceptible I/St and resistant A/Sn inbred mice.

SETTING: The availability and appropriate use of animal models is of significant importance for a better and more detailed understanding of the genetic, immunological and pathological mechanisms underlying the development of mycobacterial disease in humans. OBJECTIVE: To define a mouse model for tuberculosis severity that can be easily adapted to genetic and immunological analysis of host response to Mycobacterium tuberculosis infection. DESIGN: We describe here two inbred strains of mice, I/St and A/Sn (both Nramp1'), that differ vastly in commonly used parameters of susceptibility to infection with virulent and attenuated strains of M. tuberculosis. RESULTS: Following infection with a high dose of virulent H37Rv. M. tuberculosis and compared to their resistant A/Sn counterparts, I/St mice displayed more than a 2-fold shorter mean survival time and a more rapid onset and progression of severe body weight loss (cachexia). Moreover, I/St mice supported 20-100-fold higher multiplication of M. tuberculosis following challenge with H37Rv over a large range of infectious inocula. The high susceptibility of I/St mice was also reflected by more severe lung histopathology as evidenced by larger and more numerous lung granuloma and macrophage dominated cellular infiltrates. Finally, we determined that I/St are also unable to control infection with attenuated H37Ra M. tuberculosis and two strains of M. bovis (BCG and Ravenel) indicating hyper-susceptibility of the I/St mouse strain to mycobacterial infections. CONCLUSIONS: The results of our experiments suggest that comparative analysis of resistant A/Sn and susceptible I/St mice provides an ideal way to study host dependent aspects of tuberculosis susceptibility under the controlled conditions provided by an animal model.

Animals↗
PubMed2001

[Basic principles of enteral nutrition, tube techniques, percutaneous endoscopic gastrostomy].

Cachexia of malignancy is a heterogenous and dynamic phenomenon. Thirty to fifty percent of all oncologic patients suffer from malnutrition. Patients with ENT carcinomas, from the clinical view-point, are clearly high-risk patients. Essentially, malnutrition in ENT carcinoma patients is attributable to reduced or even insufficient energy supply and intake of nutrients as a result of pain experienced in swallowing and constrictions of the upper swallowing tract. Malnutrition has turned out to be a factor entailing an unfavourable prognosis and, frequently, limiting a therapy. In a survey conducted by the Endoscopy Working Group of the German Society for Otorhinolaryngology, Head and Throat Surgery, 70% of the university ENT hospitals confirmed that their patients experienced a clinically relevant weight loss in the range from 3 to 10 kg during oncologic causal treatment. Tube feeding with liquid formula diets is the most efficient, least-risk approach to long term use, and should already be adopted prior to therapy irrespective of scheduled oncologic causal therapy. The feeding tube placed by percutaneous endoscopically controlled gastrostomy is increasingly becoming an alternative to a nasogastric tube. Two basic PEG techniques have been employed: 1. the transoral pull technique and 2. direct puncture. In direct puncture, as distinct from the pull technique, iatrogenic dispersal of tumour cells from the primary location of the tumour with subsequent implantation in the gastric or abdominal wall is definitely ruled out. In the ENT Clinic of Magdeburg University, we decided to adopt direct puncture and, since 1991, this technique has been used in interdisciplinary co-operation with the Magdeburg University Clinic of Gastroenterology and successfully employed in 660 patients with advanced carcinomas of the upper swallowing tract. Severe PEG-induced abdominal complications were extremely rare, observed in as little as 0.5% of the cases. For enteral feeding through PEG which maintained or even improved the nutritional status, good compliance was noted in 83% of the patients. Prior to PEG and oncologic causal therapy, 36% of the patients showed malnutrition (BMI < 20 kg/m2). At the stage of anamnesis half of the patients indicated that, for the past six months prior to diagnosis of the tumour, they had experienced a weight loss of more than 10% of the calculated ideal body weight. Prior to therapy, 97% of the patients complained of dysphagia-induced reduced or impaired food intake. The various PEG tube techniques, along with their pros and cons, as well as nutritional aspects in oncology are presented for the Magdeburg patients and discussed.

Cachexia↗
PubMed1998

Esophageal involvement in cicatricial pemphigoid.

We report on a 17-year-old male patient with dysphagia, cachexia, and physical underdevelopment. Despite a known esophageal stenosis, the patient received several months of psychiatric treatment, which failed to improve the clinical picture. After systematic diagnostic procedures, including repeated biopsies of the esophageal stenosis, a cicatricial pemphigoid was diagnosed and adequate therapy could be initiated.

Adolescent↗
PubMed2001

Uric acid in cachectic and noncachectic patients with chronic heart failure: relationship to leg vascular resistance.

BACKGROUND: Chronic heart failure (CHF) is a hyperuricemic state, and capillary endothelium is the predominant site of xanthine oxidase in the vasculature. Upregulated xanthine oxidase activity (through production of toxic free radicals) may contribute to impaired regulation of vascular tone in CHF. We aimed to study the relationship between serum uric acid levels and leg vascular resistance in patients with CHF with and without cachexia and in healthy control subjects. METHODS: In 23 cachectic and 44 noncachectic patients with CHF (age, 62 +/- 1 years, mean +/- SEM) and 10 healthy control subjects (age, 68 +/- 1 years), we assessed leg resting and postischemic peak vascular resistance (calculated from mean blood pressure and leg blood flow by venous occlusion plethysmography). RESULTS: Cachectic patients, compared with noncachectic patients and control subjects, had the highest uric acid levels (612 +/- 36 vs 459 +/- 18 and 346 +/- 21 micromol/L, respectively, both P <.0001) and the lowest peak leg blood flow and vascular reactivity (reduction of leg vascular resistance from resting to postischemic conditions: 83% vs 88% and 90%, both P <.005). In all patients, postischemic vascular resistance correlated significantly and independently of age with uric acid (r = 0.61), creatinine (r = 0.47, both P <.0001), peak VO2 (r = 0.34), and New York Heart Association class (r = 0.33, both P <.01). This correlation was not present in healthy control subjects (r = -0.04, P =.9). In multivariate and stepwise regression analyses, serum uric acid emerged as the strongest predictor of peak leg vascular resistance (standardized coefficient = 0.61, P <.0001) independent of age, peak VO2, creatinine, New York Heart Association class, and diuretic dose. CONCLUSIONS: Hyperuricemia and postischemic leg vascular resistance are highest in cachectic patients with CHF, and both are directly related independent of diuretic dose and kidney function. The xanthine oxidase metabolic pathway may contribute to impaired vasodilator capacity in CHF.

Adult↗
PubMed1997

Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene.

A cellular disintegrin and metalloproteinase (ADAM) is a new family of genes with structural homology to the snake venom metalloproteinases and disintegrins. We screened genes which were selectively expressed in the cachexigenic colon 26 adenocarcinoma subline in vivo. It was found that one novel cDNA clone, identified as a cachexigenic tumor selective gene, encodes a cysteine-rich protein which shows a sequence similarity to that of both the snake venom metalloproteinases and thrombospondins. We named this cDNA clone A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1). ADAMTS1 consists of six domains, 1) a pro- and 2) a metalloproteinase, 3) a disintegrin-like, 4) a thrombospondin (TSP) homologous domain containing TSP type I motif, 5) a spacer region, and 6) COOH-terminal TSP submotifs. Unlike other ADAMs, ADAMTS-1 does not possess a transmembrane domain and is a putative secretory protein. Therefore, ADAMTS-1 is a new type of ADAM family protein with TSP type I motifs. We demonstrated that the TSP homologous domain containing the TSP type I motif of ADAMTS-1 is functional for binding to heparin. ADAMTS-1 mRNA could be induced by stimulating colon 26 cells with an inflammatory cytokine, interleukin-1, in vitro. Moreover, intravenous administration of lipopolysaccharide in mice selectively induced ADAMTS-1 mRNA in kidney and heart. These data suggest that ADAM-TS-1 may be a gene whose expression is associated with various inflammatory processes as well as development of cancer cachexia.

ADAM Proteins↗
PubMed2002

Tumor necrosis factor-regulated biphasic activation of NF-kappa B is required for cytokine-induced loss of skeletal muscle gene products.

NF-kappaB activation is classically defined as a transient response initiated by the degradation of IkappaB inhibitor proteins leading to nuclear import of NF-kappaB and culminating with the resynthesis of IkappaBalpha and subsequent inactivation of the transcription factor. Although this type of regulation is considered the paradigm for NF-kappaB activation, other regulatory profiles are known to exist. By far the most common of these is chronic or persistent activation of NF-kappaB. In comparison, regulation of NF-kappaB in a biphasic manner represents a profile that is scarcely documented and whose biological significance remains poorly understood. Here we show using differentiated skeletal muscle cells, that tumor necrosis factor (TNF) induces NF-kappaB activation in a biphasic manner. Unlike the first transient phase, which is terminated within 1 h of cytokine addition, the second phase persists for an additional 24-36 h. Biphasic activation is mediated at both the levels of NF-kappaB DNA binding and transactivation function, and both phases are dependent on the IKK/26 S proteasome pathway. We find that regulation of the first transient phase is mediated by the degradation and subsequent resynthesis of IkappaBalpha, as well as by a TNF-induced expression of A20. Second phase activity correlates with persistent down-regulation of both IkappaBalpha and IkappaBbeta proteins, derived from a continuous TNF signal. Finally, we demonstrate that inhibition of NF-kappaB prior to initiation of the second phase of activity inhibits cytokine-mediated loss of muscle proteins. We propose that the biphasic activation of NF-kappaB in response to TNF may play a key regulatory role in skeletal muscle wasting associated with cachexia.

Animals↗
PubMed1996

Oxymetholone promotes weight gain in patients with advanced human immunodeficiency virus (HIV-1) infection.

The effect of the testosterone derivative oxymetholone alone or in combination with the H1-receptor antagonist ketotifen, which has recently been shown to block tumour necrosis factor alpha (TNF alpha), on weight gain and performance status in human immunodeficiency virus (HIV) patients with chronic cachexia was evaluated in a 30-week prospective pilot study. Thirty patients were randomly assigned to either oxymetholone monotherapy (n 14) or oxymetholone plus ketotifen (n 16). Patients receiving treatment were compared with a group of thirty untreated matched controls, who met the same inclusion criteria. Body weight and the Karnofsky index, which assesses the ability to perform activities of daily life, and several quality-of-life variables were measured to evaluate response to therapy. The average weight gain at peak was 8.2 (SD 6.2) kg (+ 14.5% of body weight at study entry) in the oxymetholone group (P < 0.001), and 6.1 (SD 4.6) kg (+10.9%) in the combination group (P < 0.005), compared with an average weight loss of 1.8 (SD 0.7) kg in the untreated controls. The mean time to peak weight was 19.6 weeks in the monotherapy group and 20.8 weeks in the combination group. The Karnofsky index improved equally in both groups from 56% before to 67% after 20 weeks of treatment (P < 0.05). The quality of life variables (activities of daily life, and appetite/nutrition) improved in 68% (P < 0.05) and 91% (P < 0.01) of the treated patients respectively. Oxymetholone was safe and promoted weight gain in cachectic patients with advanced HIV-1 infection. The addition of ketotifen did not further support weight gain. These results suggest the need for a randomized, double-blind, placebo-controlled multicentre trial.

Acquired Immunodeficiency Syndrome↗
PubMed1978

Meeting exceptional nutritional needs. 2. Elemental enteral alimentation.

Elemental enteral alimentation (EEA) is an alternative to parenteral nutrition in patients with a functioning gastrointestinal tract and increased caloric requirements or in whom regular oral feeding is impossible or impractical. EEA is given by nasogastric, jejunostomy, or gastrostomy tube. It is useful in cases of short-gut syndrome, pancreatic disease, partial intestinal obstruction, colitis, neuropsychiatric cachexia, trauma, fistula, vascular insult, and renal and liver disease, as well as in patients being prepared for surgery or requiring hyperalimentation after surgery or abdominal irradiation. Strict attention must be paid to fluid and electrolyte status and to blood and urine glucose levels in patients receiving EEA. With use of a nasogastric tube, infection of the middle ear is a possible but uncommon complication.

Cachexia↗
PubMed1985

Nutritional therapy in advanced cancer. Setting realistic goals.

Cancer cachexia is a complex syndrome resulting from metabolic disturbances, mechanical obstacles, and behavioral alterations. Assessments of the potential benefits of nutritional support for an individual patient must reflect the cancer stage and prognosis, the patient's expressed wishes, and the impact of treatment on the family unit. Enteral or parenteral alimentation may preserve body mass during aggressive, potentially curative therapy of early cancer. Palliation may be provided for the more advanced patient whose major problem is not being able to eat. In terminal illness, feeding may no longer be therapeutic--it may briefly prolong life with considerable morbidity and expense. At each stage, decisions should be based on realistic assessments of possible gains and losses to the patient's life and overall well-being.

Anorexia↗
PubMed1987

Hydrazine sulfate: a current perspective.

Hydrazine sulfate is an anticachexia agent which interrupts host energy wasting as a result of the malignant process. An inhibitor of gluconeogenesis at the phosphoenolpyruvate carboxykinase (PEP CK) reaction, this agent has been shown in randomized, placebo-controlled, double-blind trials to improve glucose tolerance, reduce glucose turnover, increase caloric intake, and increase or stabilize weight; in single-arm controlled trials, this agent has been shown to increase appetite, improve performance status, decrease pain, diminish anorexia, normalize laboratory indices, stabilize tumor growth, induce tumor regression, and promote survival, while inducing little to no important clinical side effects. In view of its demonstrated capacity to effect anticancer response, this drug is suggested for trial as a sole agent in early drug-resistant cancer, in combination with cytotoxic and related therapies, and in conjunction with total parenteral nutrition. It is postulated that effective control of the mechanisms associated associated with cancer cachexia may contribute to control of malignant disease.

Cachexia↗
PubMed1993

Alterations in postprandial glycogen and lipid synthesis in cachectic tumor-bearing rats.

Alterations in the postprandial metabolism of glucose were investigated in groups of tumor-bearing rats and freely fed controls and in groups of normal rats whose food intake had been restricted to match that of the tumor-bearing rats. A standard mixed meal was administered by gavage, and the rate of incorporation of 3H from 3H2O into hepatic glycogen and into saponifiable lipids in the liver and adipose tissue was measured at intervals up to three hours after the meal. In tumor-bearing rats, the rate of glycogen synthesis rose by more than twice as much as normal after the meal, while the normal rise in rates of fatty acid synthesis was suppressed. In contrast, in the rats whose food intake had been restricted, the postprandial rise in hepatic glycogenesis was suppressed and the rates of postprandial lipogenesis in liver and adipose tissue were increased. Thus the changes that were observed in the tumor-bearing animals did not represent a normal response to reduced food intake. Increased postprandial glycogenesis in tumor-bearing rats is likely to be associated with increased gluconeogenesis, thereby increasing energy expenditure. The prolonged high rate of hepatic glycogen synthesis may also delay the initiation of the next meal and thus contribute to the decrease in food intake in cancer cachexia.

Animals↗
PubMed1999

Tumor necrosis factor-alpha serum activity during treatment of acute decompensation of cachectic and non-cachectic patients with advanced congestive heart failure.

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that produces left ventricular dysfunction and a negative inotropic effect in cardiac tissue when overexpressed in human subjects. Previous studies have shown that levels of circulating TNF-alpha are elevated in patients with advanced congestive heart failure (CHF) and especially in those with cardiac cachexia. To clarify the potential role of TNF-alpha in the unstable state of decompensated advanced CHF, we investigated the TNF-alpha serum activity in 25 cachectic and 22 non-cachectic CHF patients (New York Heart Association, NYHA functional classes III or IV), who were treated with intravenous diuretics and positive inotropic agents for acute decompensation of the disease, during a 5-day hospitalization period, as well as in 15 age-matched healthy control subjects. Cachectic CHF patients needed higher dosages of inotropic agents than non-cachectic patients and the determination of TNF-alpha serum concentrations in this patient group showed high levels of TNF-alpha at hospital admission (18.3 +/- 3.2 pg/ml) and a transient increase in circulating TNF-alpha during the treatment period with the highest levels on the 2nd day of hospitalization (32.5 +/- 7.1 pg/ml). The TNF-alpha serum levels were low in non-cachectic CHF patients and healthy controls on the 1st day (4.0 +/- 0.9 and 3.7 +/- 0.6 pg/ml, respectively) and did not change substantially during the course of the study. The present results show that TNF-alpha serum activity is transiently increased during the treatment of decompensated cachectic CHF patients only and may be related to the clinical instability and the consequent therapeutic interventions in this category of CHF patients.

Acute Disease↗
PubMed1998

Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: effect of indomethacin treatment.

The syndrome of cancer cachexia is accompanied by several alterations of lipid metabolism, especially that in the liver. In this study we have investigated a possible mechanism whereby the presence of the Walker 256 carcinosarcoma affects hepatic fatty acid oxidative capacity in tumour-bearing rats. Hepatic mitochondrial outer membrane carnitine palmitoyltransferase I (CPT I), generally accepted as the main site of regulation of fatty acid oxidation, was unaffected by the presence of the extra-hepatic tumour. However, mitochondrial inner-membrane carnitine palmitoyltransferase II (CPT II) activity was markedly decreased in mitochondria isolated from the liver of tumour-bearing rats. Immuno-detection by Western blotting using a CPT II-specific antibody identified two bands (corresponding to M(r) 69,000 and 54,000) in tumour-bearing rats whereas only the normal-sized CPT II was present (at the expected M(r) 69,000) in mitochondria from control rats. It is suggested that the emergence of the second, smaller protein may represent a catalytically less active protein that arises in vivo, since its appearance was not affected by the inclusion of proteolysis inhibitors in the mitochondrial preparation buffers. Treatment of the tumour-bearing rats with indomethacin, a prostaglandin (including PGE2) synthesis inhibitor, increased CPT II activity to levels even higher than those found in the control animals. It is suggested that PGE2 may play a role in the control of CPT II expression in the liver of tumour-bearing rats. Indomethacin treatment did not affect either of the two CPT activities of the mitochondria isolated from tumour tissue.

Animals↗
PubMed2004

The relationship between a urinary cachectic factor and weight loss in advanced cancer patients.

A 24K glycoprotein, the proteolysis-inducing factor (PIF), has been identified in mice and humans with cancer cachexia. Clinical cross-sectional studies found an association between the presence of PIF in urine and tumors of patients and weight loss. For the first time, we report results from a longitudinal study establishing the relationship between a urinary PIF pattern and persistent weight loss. Over time, cancer patients positive for the PIF pattern experienced weight loss, whereas those with a negative test gained weight.

Adult↗
PubMed2005

Tuberculosis, bronchiectasis, and infertility: what ailed George Orwell?

In the last and most productive years of his life, George Orwell struggled with pulmonary tuberculosis, dying at the dawn of the era of chemotherapy. His case history illustrates clinical aspects of tuberculosis with contemporary relevance: the role of poverty in its spread, the limited efficacy of monotherapy, the potential toxicity of treatment, and the prominence of cachexia as a terminal symptom. Orwell's ordeals with collapse therapy may have influenced the portrayal of the tortures of Winston Smith in the novel 1984. I discuss unifying diagnoses for Orwell's respiratory problems and apparent infertility, including tuberculous epididymitis, Young syndrome, immotile cilia syndrome, and cystic fibrosis.

Antitubercular Agents↗