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PubMed1989

[Tumor necrosis factor alpha (cachectin). Biological properties and role in physiopathology].

Cachectin, or TNF-alpha (tumor necrosis factor alpha) was first described as a product of activated monocytes capable of inducing tumor cell lysis both in vitro and in vivo. In addition to this activity, TNF-alpha has been shown to possess many other biological properties: it modulates the synthesis of the enzymes involved in lipogenesis and regulates the function of various types of normal cells, such as fibroblasts, osteoblasts, endothelial cells and adipocytes. Moreover, TNF-alpha - displays multifunctional immunoregulatory activity on T and B lymphocytes and on natural killer and lymphokine activated killer cells and plays a major role in the defence against infections and in the immune response against cancer. In severe infection or cancer, an excessive production of TNF-alpha may be responsible for septic shocks or cachexia in both animals and man. The high conservation of the TNF-alpha gene in all species despite its toxicity indicates that it plays a crucial but still partially understood role.

Animals↗
PubMed1989

Tumour necrosis factor: clinical relevance.

The anticancer effect of tumour necrosis factor (TNF) in murine tumours and in vitro has stimulated great enthusiasm for investigating its possible therapeutic role in humans. Results have now indicated that 400-800 micrograms ng/m2 of TNF may be given to patients and further dose increases are limited by hypotension and hepatic damage. At this dose, no consistent anticancer effects have yet been seen and measurement of TNF serum concentrations suggests that these effects are less than those required to induce regression of mouse tumours. TNF as a single agent is unlikely to have a major role in the treatment of cancer in humans and further studies will explore combination with other agents. During the investigation of the clinical role of TNF, observations have clarified its biological role as a mediator of inflammation and shock, cachexia and organ dysfunction.

Animals↗
PubMed1989

Persistence of the hypertriglyceridemic effect of tumor necrosis factor despite development of tachyphylaxis to its anorectic/cachectic effects in rats.

The administration of a single injection of tumor necrosis factor (TNF) produces a variety of acute and sustained biological effects, including hyperlipidemia, stimulation of hepatic lipogenesis, decreases in adipose tissue lipoprotein lipase activity, and anorexia with weight loss. Chronic administration of a fixed dose of TNF produces tachyphylaxis to the anorectic/cachectic effects of TNF. We now report that the hyperlipidemic effect of TNF persists during chronic TNF administration in the absence of any cachectic effect of TNF. Sprague-Dawley rats injected with TNF (250 micrograms/kg) show a significant decrease in weight over the next 24 h which can be accounted for by decreases in food and water intake accompanied by an increase in urine output. With subsequent daily injections of TNF, treated rats begin eating and rapidly regain weight. Hypertriglyceridemia persists for up to 10 days of daily injections of TNF. After three daily injections of TNF, no decreases were seen in lipoprotein lipase activity in a wide variety of tissues. De novo hepatic lipogenesis remained increased in TNF-treated animals after four daily injections, but by the fifth day hepatic lipogenesis returned to normal. After 5 days of TNF treatment the acute incorporation of labeled glycerol into serum triglycerides remained elevated. These data indicate that hyperlipidemia persists during multiple daily injections of TNF and that TNF induced hypertriglyceridemia is not inevitably linked to the syndrome of cachexia.

Animals↗
PubMed1989

Gelatinous transformation of bone marrow in systemic lupus erythematosus.

Gelatinous transformation of marrow is a rare disease entity described in cachexia and various other disorders. Its association with systemic lupus erythematosus (SLE) has never been reported. We found gelatinous transformation in 3 of 30 patients with SLE with pancytopenia. Two of these patients were cachetic, one of whom also had active tuberculosis. We propose that gelatinous transformation can be associated with SLE, and its detection calls for an evaluation of nutritional status, and a search for chronic debilitating infections such as tuberculosis.

Adult↗
PubMed1986

Malnutrition and the heart.

Earlier concepts that the heart is spared in malnutrition have been shown to be incorrect. Inadequate intake of protein and energy results in proportional loss of skeletal and myocardial muscle. As myocardial mass decreases, so does the ability to generate cardiac output; however, various compensatory factors come into play. Nutritional supplementation for malnourished patients reverses the compensatory factors and may increase the short-term potential for heart failure. Severe cardiac debility results in poor nutrition, which may in turn produce unsuspected but clinically significant myocardial atrophy. Nutritional support may play a role in improving cardiac function in selected patients with cardiac cachexia who are being prepared for cardiac surgery and in patients with rapid weight loss who are at risk for sudden death due to arrhythmias. Malnutrition is common in hospitalized patients, and many patients in hospital now receive nutritional supplementation; both facts have important cardiac implications.

Animals↗
PubMed1988

[The clinical picture of postpartum hypopituitarism].

Hypopituitarism depends on the history of the obstetric cause, on the subsequent amenorrhoea and the usual absence of lactation, on the biochemical abnormalities found later, and on the effect of therapy. Nevertheless, an initial clinical inspection of the untreated patient gives important clues to the diagnosis. Cachexia does not occur in true hypopituitarism, unless there is some intercurrent factor which causes emaciation, such as carcinoma, tuberculosis, ulceration in the alimentary tract etc.

Amenorrhea↗
PubMedDate not supplied

[Construction of a jejunal pouch using stapling technics in total gastrectomy].

During the last four years we performed 16 total gastrectomies with construction of a jejunal pouch. The idea was that patients with a pouch should be able to eat larger meals. This was affirmed by the patients, also there were no complaints of regurgitation. Cachexia was not observed in the disease-free patients. Nevertheless the life expectancy stays poor. A description of the technique is given.

Adult↗
PubMed1987

Gluconeogenesis in the tumor-influenced rat hepatocyte: importance of tumor burden, lactate, insulin, and glucagon.

In an attempt to define the relationship between tumor burden (cachexia) and host hepatocyte gluconeogenesis, the following experiments were performed with the use of an F344 male rat bearing a transplantable sarcoma. Food intake of tumor-bearing (TB) rats was constant until day 24 following implant and a tumor burden of 18 +/- 5.2% (mean +/- SD), at which time food intake progressively declined daily. Tumor burden was arbitrarily divided at 12.8% to determine if any measured changes occurred prior to or following the approximate time when a significant decline in food intake occurred. Plasma glucose levels decreased with tumor burden. Whole-blood lactate levels increased with tumor burden. Fasting plasma alanine levels decreased with tumor burden. Plasma 3-methylhistidine levels increased with tumor burden. Plasma glucagon levels increased with tumor burden, whereas plasma insulin levels decreased. Hormone changes were noted at small tumor burdens prior to a decline in food intake. Viable hepatocytes were isolated from 4 groups: non-tumor-bearing (NTB), small tumor burden [(STB) 3.5% total body weight (TBW)], moderate tumor burden [(MTB) 14% TBW], and large tumor burden [(LTB) 23% TBW]. As expected in NTB rats, hepatocytes produced significantly more glucose with 20 mM lactate than 20 mM alanine or than Hanks' balanced salt solution (HBSS) alone. Hepatocytes from STB rats demonstrated the same basic relationship for lactate, alanine, and HBSS, but they produced significantly more glucose from lactate and HBSS alone than NTB hepatocytes. With alanine as substrate, the rates of glucose production by hepatocytes were not affected by the presence or size of tumor. However, with lactate as substrate, hepatocytes from MTB and LTB rats produced progressively less glucose as tumor burden increased (r = -0.85, p less than .001), which may partly explain the reduction in blood glucose and elevation in blood lactate levels observed. Elevated gluconeogenesis in TB rats occurred early prior to a decline in food intake. The key precursor appeared to be lactate. The balance between glucagon and insulin appeared to promote the abnormal host carbohydrate metabolism observed.

Amino Acids↗
PubMed1986

Protein turnover states of tumour cells and host tissues in an experimental model.

To investigate the progress of tissue protein metabolic perturbations in animals developing cancer cachexia, we analyzed an experimental model system based on a highly-deviated, transplantable ascites hepatoma of the rat (Yoshida AH-130). After inoculation, at first this tumour grew rapidly at an exponential rate, then it entered a stationary state until animal death (in about 15 days). Cessation of protein accumulation (growth) was achieved by tumour cells thanks to a combined reduction of synthesis and enhancement of protein degradation (slow-turnover protein pool); the latter was apparently operated through activation of the acidic vacuolar (lysosomal) mechanism. The body weight, net of tumour, early and progressively declined in transplanted rats. Their liver initially showed a moderate enlargement, mostly accounted for by a reduction in the protein breakdown rate; then the liver eventually atrophied, in spite of an enhanced synthetic rate, because of an even greater increase of the degradative rate. By contrast, gastrocnemius muscles started loosing weight and protein since the early phases of tumour growth; their atrophy was associated with elevation of the apparent protein degradative rate, with no change in the apparent synthetic rate. Therefore, tumour growth somehow elicited perturbations in the host tissues examined, which apparently mostly affected the catabolic side of protein turnover.

Animals↗
PubMed1987

Resting energy expenditure and body cell mass alterations in noncachectic patients with sarcomas.

Resting energy expenditure (REE), body cell mass (BCM), and body fat (BF) were measured in six male and seven female volunteers and in a homogeneous group of noncachectic patients with sarcoma, (n = 7). The patients all had large localized tumors, no history or clinical evidence of decreased food intake or weight loss, and had received no prior treatment for cancer. Indirect calorimetry (for REE), K40 analysis (for BCM), and anthropometric measurements (for BF) were performed in accordance with established methods. Physical activity and nutritional status were also assessed. As expected, female control subjects had 50% greater percent BF (p less than 0.001) and 13% less percent BCM (p less than 0.01) than male controls. Male patients with sarcoma had equivalent percent BF, but significantly less percent BCM than controls matched for age, sex, and body surface area (BSA) (p less than 0.05). The REE corrected for BSA was similar in male and female controls but was 25% greater in male sarcoma patients than in male controls (p less than 0.05). This difference was doubled when REE was corrected for BCM (p less than 0.01). In patients with sarcomas, REE/BSA varied inversely with percent BCM (r = -0.782; p less than 0.05) while a similar relationship was not observed in healthy volunteers. We conclude that both REE and vital, functional BCM can be significantly altered in sarcoma patients before any overt signs of cachexia develop. The results support the contention that sarcoma alters host energy metabolism and causes abnormal body composition.

Adult↗
PubMed1986

Effects of tumor type and burden on carcass lipid depletion in mice.

Cancer bearing is frequently accompanied by weight loss, yet the factors causing cancer cachexia remain unclear. This study compares how tumor type and tumor burden affect host carcass fat depletion. Nude mice were inoculated with human malignant melanoma, human colon adenocarcinoma, or murine sarcoma cells, or were noninjected controls. Body weights, tumor burdens, and carcass lipid contents were measured. Carcass weights of melanoma-bearing mice were significantly lower than those of sarcoma-bearing mice, mice exposed to colon cancer antigens but without tumor growth, or control mice (all p less than 0.02). The degree of carcass lipid loss in melanoma-bearing mice (mean tumor burden 3.5% of total body weight [TBW]) was almost three times that of sarcoma-bearing mice (p less than 0.05), which had more than twice the tumor burden (mean tumor burden 7.8% TBW). Exposure to colon cancer antigens without tumor growth resulted in essentially no carcass lipid depletion compared with control mice. These findings argue against a mass effect of tumor as being solely responsible for host fat mobilization and suggest that carcass lipid depletion in tumor-bearing nude mice is more a function of tumor type than of tumor burden.

Adenocarcinoma↗
PubMed1986

Appetite stimulation with megestrol acetate in cachectic cancer patients.

Cachexia is often a severe problem in the management of cancer and other illnesses because it adds to the morbidity of the underlying disease and complicates its treatment. Megestrol acetate has been observed anecdotally to produce weight gain. A review of our experience, and our ongoing phase I/II study of high-dose megestrol acetate for breast cancer, revealed that weight gain occurred in nearly one third (27%) of patients at conventional doses (160 mg/d), and that a marked weight gain (median, 5.1 kg; range, 0.9 to 20.1 kg) occurred in 27 of 28 patients with breast cancer during treatment with high doses of megestrol acetate. Subjective improvement in appetite occurred in most patients at low doses and in most patients at high doses. Further, nearly one half (48%) of patients at conventional doses and virtually all patients at high doses experienced an increased sense of well-being. Our data suggest that megestrol acetate has a potential role in producing subjective improvement, sense of well-being, and increase in appetite and weight, and that the effect may be dose related. Further research is necessary to understand the mechanism of appetite stimulation and/or anabolic effect.

Adult↗
PubMedDate not supplied

[Epilepsy with myoclonic-astatic attacks (Lennox-Gastaut syndrome) with particularly unfavorable course].

Out of over 100 children with the Lennox-Gastaut syndrome observed in the Outpatient Clinic and Department of Paediatric Neurology, Children's Health Center the authors present 6 cases in which the course of the disease was progressive and devastating. The main signs were astatic-myoclonic and generalized seizures, regression of psychomotor development, followed by mental regression, pareses of extremities, decortication symptoms and somatic cachexia. The authors suggest that the clinical course, the character of epileptic seizures very poor prognosis in certain children with the Lennox-Gastaut syndrome make the syndrome similar in its clinical aspects to subacute sclerosing panencephalitis and require careful differential diagnosis for excluding the latter disease.

Cachexia↗
PubMed1985

Glycerol dynamics in weight-losing cancer patients.

This study was designed to show whether weight-losing cancer patients have an elevated glycerol turnover. Four groups of patients were examined: weight-losing cancer patients, weight-losing patients without cancer, cancer patients without weight loss, and weight-stable and well-nourished hospitalized control patients. Glycerol was infused intravenously at three different rates (200, 400, and 800 mumol/hr/kg body weight) after an overnight fast. This allowed measurement of clearance and plasma glycerol turnover. Weight-losing cancer patients (group 1) had an almost threefold higher glycerol turnover per kilogram of body weight compared with malnourished and well-nourished noncancer patients. However, both malnourished cancer and noncancer patients had an elevated glycerol turnover compared with well-nourished patients when glycerol turnover was related to whole body lipids. The results how that progressive clinical cancer is associated with an elevated plasma glycerol turnover, probably indicating an increased whole body lipolysis. This may explain the loss of body fat during the development of cancer cachexia.

Aged↗
PubMed1977

Spinal cord infarction following therapeutic renal artery embolization.

A patient with dialysis cachexia became paraparetic within hours of therapeutic renal artery embolization. At autopsy, emboli of absorbable gelatin sponge filled spinal arteries, accompanied by spinal cord infarcts. The renal arteries of patients with end-stage renal disease are smaller than normal becaue of intimal fibrosis associated with prolonged dialysis. Embolic material can reflux more readily in these patients than in patients with renal tumors.

Adult↗
PubMed1977

[Do lithium salts have a place in the treatment of severe hyperthyroidism? (author's transl)].

In a patient with hyperthyroidism resulting in cachexia, severe cardiac complications and functional renal failure, and a second case of hyperthyroidism refractory to carbimazole as a result of iodine overload, the administration of 1 to 3 g of lithium gluconate every 1 to 3 days, in association with carbimazole, led to persistent clinical and biological improvement in 8 to 16 days. In the first case, the course was complicated by neurological intolerance (blood lithium 0.98 mEq/l) which responded to the temporary interruption of treatment and by a transient escape of thyroid function from the effects of lithium which disappeared after a slight adjustment in the dose. In the second case, the course under treatment was favourable from the outset. Thus in forms of hyperthyroidism in which usual forms of treatment are inadequate and where there is a risk of "acute crises", lithium may be valuable as adjuvant therapy. If the dose is regularly modified in order to obtain a daily blood lithium level of less than 0.60 mEq/l, and on condition of close clinical, electrocardiographic and ionic surveillance, cardiac and renal failure and neuropsychiatric disturbances do not prevent the use of lithium, which the authors feel to be of irreplaceable value.

Aged↗
PubMed1984

[Sarcoidosis in a child disclosed by blindness with major hypercalcemia].

We report here a case of sarcoidosis, observed in a 12 year-old algerian girl. When the child was examined, at an advanced stage of the disease, her clinical condition was very critical, associating blindness, cachexia, hepatic and splenic enlargement, and major hypercalcaemia. Though chest roentgenograms were normal, the results of both functional pulmonary tests and broncho-alveolar lavage were pathologic. The diagnosis of sarcoidosis was confirmed by the finding of an elevated level of Angiotensin-converting enzyme, and by histologic lesions observed in liver, kidney and conjunctiva biopsies. The corticosteroid treatment improved the general condition, but it failed to better the visual state.

Blindness↗