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PubMedDate not supplied

[Leptin: regulatory role in bone metabolism and in inflammation].

Leptin is a peptidic molecule synthesized almost exclusively by adipocytes, that regulates appetite and energy expenditure at the hypothalamic level. In the last few years, further actions have been attributed to this molecule, as modulating the immune response and affecting the bone metabolism. We have reviewed if leptin contributes to the metabolic changes leading to cachexia and to the regulation of inflammation, paying attention to the pathogenetic mechanisms of chronic arthritis. Besides, considering the relationship between body mass index (BMI) e bone mineral density (BMD) and the protective role of the obesity towards osteoporosis, we have analysed the role of leptin on the bone metabolism

Adipocytes↗
PubMed1994

Increased resting metabolic rate in patients with congestive heart failure.

OBJECTIVE: To examine resting metabolic rate in patients with congestive heart failure as a cause of cardiac cachexia and associated weight loss. DESIGN: Cross-sectional study. SETTING: Baltimore Veterans Affairs Medical Center. PATIENTS: 20 men with heart failure (mean age +/- SD, 69 +/- 7 years) and reduced ejection fraction (mean, 0.24 +/- 0.10) and 40 healthy men (mean age, 69 +/- 7 years). RESULTS: Patients with heart failure had smaller fat-free mass than did controls (53 +/- 8 kg compared with 56 +/- 6 kg; P < 0.09), but no difference in fat mass existed (21 +/- 8 kg compared with 19 +/- 8 kg). Measured resting metabolic rate was 18% higher in patients with heart failure than in controls (1828 +/- 275 kcal/d compared with 1543 +/- 219 kcal/d; P < 0.01); no difference in caloric intake existed (2144 +/- 479 kcal/d compared with 2174 +/- 826 kcal/d). The difference in resting metabolic rate between the two groups was even more striking when indexed per kilogram of fat-free mass. CONCLUSIONS: Higher resting metabolic rate in patients with heart failure at least partially accounts for otherwise unexplained weight loss. Present caloric guidelines, which were established in healthy elderly persons, substantially underestimate the resting caloric needs of elderly persons with heart failure.

Aged↗
PubMed1995

Induction of adrenal suppression by megestrol acetate in patients with AIDS.

OBJECTIVE: To investigate the development of secondary adrenal suppression in a patient with the acquired immunodeficiency syndrome (AIDS) who was receiving megestrol acetate. DESIGN AND PATIENTS: Case report of one patient abruptly withdrawn from long-term therapy with megestrol acetate; prospective study of four patients with AIDS who were starting therapy with megestrol acetate for cachexia. SETTING: Outpatient clinic of a university hospital. INTERVENTIONS: Study patients received megestrol acetate, 80 mg three times daily. MEASUREMENTS: Study patients had cosyntropin-stimulation testing and oral glucose tolerance testing before and after starting therapy with megestrol acetate. RESULTS: The patient described in the case report developed symptoms of adrenal insufficiency after withdrawal of megestrol acetate after 4 years of treatment. His basal cortisol and adrenocorticotropic hormone (ACTH) levels were low. He showed an abnormally diminished response to a short cosyntropin-stimulation test but did respond to a 3-day cosyntropin-stimulation test. The morning cortisol levels of the study patients decreased significantly (from 11.0 +/- 1.8 micrograms/dL to 1.5 +/- 0.9 micrograms/dL; P < 0.01), and the ACTH levels of these patients decreased to below normal (from 16.6 +/- 5.5 pg/mL to 6.3 +/- 3.3 pg/mL; P = 0.02) during treatment with megestrol acetate. Cortisol levels after administration of cosyntropin decreased significantly (from 27.3 +/- 3.3 pg/mL to 9.3 +/- 6.3 pg/mL; P = 0.01) during treatment with megestrol acetate. The results of oral glucose tolerance testing in two patients were consistent with the development of insulin resistance, and daily insulin requirements increased 10-fold in a patient who had preexisting diabetes. CONCLUSIONS: Prolonged administration of megestrol acetate can induce clinically significant secondary adrenal suppression, and abrupt withdrawal of megestrol acetate after prolonged administration can cause adrenal insufficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Inhibition of prostate cancer metastasis in vivo: a comparison of 1,23-dihydroxyvitamin D (calcitriol) and EB1089.

The steroid hormone 1,25-dihydroxyvitamin D [1,25(OH)2D, also known as calcitriol] is known to inhibit the proliferation and to promote the differentiation of human prostate cancer cells. Additionally, we showed that 1,25(OH)2D markedly inhibits the invasiveness of human prostate cancer cells in vitro (G. G. Schwartz et al., Cancer Epidemiol. Biomark. Prev., 6: 727-732, 1997). These properties support the use of 1,25(OH)2D as differentiation therapy in prostate cancer. However, the use of 1,25(OH)2D in vivo is limited by the risk of hypercalcemia. We therefore compared the effects of 1,25(OH)2D and of EB1089, an analogue of 1,25(OH)2D with reduced calcemic effects, in an in vivo model of androgen-insensitive metastatic prostate cancer, the rat Dunning MAT LyLu prostate cancer model. Tumor growth and metastasis were studied using Copenhagen rats given s.c. injections of MAT LyLu cells. Fifty male rats were divided into five groups of 10 rats each. Four experimental groups received i.p. injections of low and high doses of 1,25(OH)2D and EB1089 (0.5 and 1.0 microg/kg, low and high, respectively). A control group received injections of vehicle only. Tumor volumes were measured three times per week. Rats were weighed weekly. The number of metastases to the lungs and the extent of hypercalcemia were evaluated. Compared with controls, tumor volumes were significantly smaller in all experimental groups. Similarly, the number of lung metastases (number of foci/lung) was reduced markedly by both 1,25(OH)2D and EB1089. Control rats developed 22.7 (+/- 1.98 SE) tumor foci per lung. Rats treated with 1,25(OH)2D and with EB1089 (1.0 microg/kg) developed 10.4 (+/- 2.81) and 7.70 (+/- 1.29) tumor foci, respectively (P < 0.001 and P < 0.0001, respectively; drug versus control). Compared with controls (10.79 +/- 0.1 mg/dl), serum calcium levels were significantly elevated in both 1,25(OH)2D and EB1089-treated rats (P < 0.01). However, EB1089 was significantly less calcemic than 1,25(OH)2D (12.59 +/- 0.21 mg/dl versus 14.47 +/- 0.46 mg/dl; 1.0 microg/kg; P < 0.001). Rats treated with 1,25(OH)2D showed marked weight loss: 20.0 +/- 1.9% and 26.3 +/- 1.7% of their initial weight (low and high doses, respectively, P < 0.001). Weight loss was significantly lower in rats treated with EB1089 at the high dose 8.4 (+/- 2.9) %. Moreover, rats treated with low-dose EB1089 gained 5.2 (+/- 3.7) % of their initial weight. In conclusion, 1,25(OH)2D and EB1089 showed marked and equivalent inhibition of prostate cancer metastasis in vivo. EB1089 was significantly less calcemic than 1,25(OH)2D and did not induce severe weight loss. This is the first report of a vitamin D analogue that significantly inhibits prostate cancer metastasis in vivo and that does so without producing cachexia or unacceptable hypercalcemia.

Animals↗
PubMed1997

Weight loss in cancer patients can be offset by aggressive nutritional therapy.

Patients with cancer or other debilitating diseases such as AIDS and COPD often have on and off interruptions in care because of cachexia, also known as wasting syndrome. However, managing these patients with "medical foods" can and does get them on their feet faster. Find out how and why some doctors are swearing by this not so well-known management tool.

Cachexia↗
PubMed1999

Palliative care and AIDS: 2--Gastrointestinal symptoms.

With the use of more intensive antiretroviral therapies (highly-active antiretroviral therapy, HAART) particularly in first world countries, reductions in the mortality and morbidity of HIV infection are being seen. However, though the prevalence of symptoms may change, symptom control does continue to be a problem for many people with HIV, particularly as their disease progresses. This is the second of 2 CME articles about palliative care and HIV infection. The first gave a background to palliative care, and covered symptom control of pain. This article gives suggestions for the treatment of common gastrointestinal symptoms in HIV infection; nausea and vomiting, cachexia and anorexia and chronic diarrhoea.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Elimination of anemia-inducing substance by cyclic plasma perfusion of tumor-bearing rabbits.

We carried out a fundamental study to search for a therapeutic modality that would remove the anemia-inducing substance (AIS) from the plasma of cancer patients because it is thought to be one of the substances responsible for anemia and immunodeficiency in advanced cancer patients. Using AIS isolated from the plasma of patients with advanced ovarian carcinoma, we confirmed that adsorption of AIS to noncoated charcoal was nonspecific and high. Moreover, it was verified that VX2 carcinoma-bearing rabbits are an optimal experimental model for plasma perfusion. The data obtained on day 40 after transplantation (hemoglobin, 9.1+/-2.1 g/dl; osmotic pressure inducing RBC lysis, 137+/-11 mosmol/kg; lymphocyte stimulation index, 8.8+/-8.6; and RBC fragility-inducing activity, 40+/-9 mosmol/kg) proved similar to the hematological findings in patients with cancer cachexia. A 1-h plasma perfusion (3 ml/min) through noncoated charcoal was performed in tumor-bearing rabbits, and it resulted in the restoration of RBC fragility-inducing activity and suppression of lymphocyte blast formation to pretransplantation values. When plasma perfusion was performed every 3 days, RBC fragility-inducing activity, which increased again 3 days after perfusion, was diminished, and RBC osmotic resistance was within the normal range from the fourth perfusion onward. These results showed that cyclic plasma perfusion is effective in sustained removal of RBC fragility-inducing factor from plasma, suggesting that it might have the potential for clinical application.

Adsorption↗
PubMed1999

The expression of genes in the ubiquitin-proteasome proteolytic pathway is increased in skeletal muscle from patients with cancer.

BACKGROUND: The intracellular mechanisms of muscle cachexia in patients with cancer are not known. To assess the role of the ubiquitin-proteasome proteolytic pathway in cancer-induced muscle breakdown, we determined messenger RNA levels for ubiquitin and several 20S proteasome subunits in muscle from patients undergoing surgery for cancer METHODS: A biopsy specimen was obtained from the rectus abdominis muscle in patients undergoing laparotomy for cancer (n = 6) or noncancer disease (n = 6). Tissue levels of mRNA for ubiquitin and the 20S proteasome subunits HC3, HC5, HC7, and HC9 were determined by dot blot analysis. RESULTS: The mRNA levels for ubiquitin and the 20S proteasome subunits were 2 to 4 times higher in muscle from patients with cancer than in muscle from control patients. CONCLUSION: This is the first report of increased expression of genes in the ubiquitin-proteasome proteolytic pathway in muscle tissue from patients with cancer. Cancer-induced muscle catabolism may at least in part reflect ubiquitin-proteasome-dependent protein breakdown.

Adult↗
PubMed1975

Causes of death in cancer patients.

Causes of death in the year 1970 were analyzed retrospectively on the basis of clinical and pathologic reports of 506 cases in the Roswell Park Memorial Institute and Hospital. The single major cause of death was infection (36%), which was also a contributory factor in an additional 68% of the cases. Other important causes of death were hemorrhagic and thromboembolic phenomena (18%), which also were contributory factors in an additional 43%. Organ invasion by neoplastic cells including hepatic failure was the major cause of death in 10% and was a contributory factor in 5%. Cachexia was reported as major cause of death in 1% and as contributory factor in 0.4%. Respiratory failure due to various causes (including aspiration) was the main mechanism of death in 19% and a contributory factor in 3%. Cardiovascular insufficiency was the major cause of death in 7% and a contributory factor in 3%.

Autopsy↗
PubMedDate not supplied

[Prevention of wasting and opportunistic infections in HIV-infected patients in West Africa: a realistic and necessary strategy before antiretroviral treatment].

The medical inequalities between countries of the North and South (infrastructure, drug availability, medical techniques) are particularly marked in terms of the challenge posed by HIV infection. We propose a strategy for monitoring adult patients in West Africa that is appropriate to the situation in the field and to economic constraints. The aim of this strategy is to increase the quality of life and the life expectancy of HIV-infected adults and to prevent the overcrowding of hospital departments with patients in the terminal phase of AIDS. We analyzed the biological and clinical spectrum of HIV infection before the onset of the diseases that define AIDS (excluding pulmonary tuberculosis). We found that it was particularly important to diagnose B-stage diseases early, especially atypical chronic cutaneous and mucous diseases. Careful analysis of data from a routine hemogram (total lymphocyte count 2500/ml; paradoxical eosinopenia), even in the absence of a CD4 lymphocyte count, should also enable clinicians from a wide variety of health structures to identify the HIV-infected patients most likely to benefit from more detailed clinical follow up, prophylaxis of opportunistic infections using cotrimoxazole, nutritional checkups and prevention of wasting. Cachexia is the most common AIDS-associated disease in West African patients. It involves an overall decrease in calorific intake, diarrhea, immune system activation, an increase in TNFalpha production and greater energy expenditure when resting. Recent nutritional studies have shown that it is vital to optimize the calorific intake of HIV-infected patients presenting with chronic diarrhea, before the onset of severe immune deficiency, to prevent wasting. So, spontaneous calorific intake should de routinely determined in HIV-infected patients and an optimal diet provided. Specific training in nutrition is required for doctors and nurses, as is consideration of the logistic organization required to provide nutritional support to HIV-infected adults. Despite the large number of individuals infected and the lack of sophisticated paraclinical facilities, we feel that it is possible to establish rational management "a minima" of HIV infection in West Africa, whilst waiting for antiretroviral drugs to become more widely available. This strategy could be of direct benefit to patients without swallowing up the financial resources of the health system in expensive biological follow up. Such basic management is also required before the new antiretroviral drugs become widely available. Research should be carried out in parallel in several reference centers in West Africa to determine the most effective associations of antiretroviral drugs and the optimal timing of treatment during the course of infection and to assess the potential side effects of these drugs in HIV patients exposed to recurrent antigenic stimulation by a wide diversity of pathogens.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

TNF alpha, IL-1 beta and IL-6 production by peripheral blood monocytes in patients with renal cell carcinoma.

Renal cell carcinoma (RCC) has been shown to be immunologically more labile than other types of cancer. In this study, we examined tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) production of peripheral blood monocytes in 38 RCC patients. Monocytes were isolated from peripheral blood mononuclear cells by adherence to a plastic dish and cultured with lipopolysaccharide for 24 hours. The culture supernatant was obtained, and the production of TNF alpha, IL-1 beta and IL-6 was measured by ELISA. As a result, TNF alpha and IL-1 beta production was significantly higher in the high stage patients compared to the control subjects and low stage patients. When the patients were divided according to serum C-reactive protein (CRP), TNF alpha, IL-1 beta and IL-6 production was significantly higher in the CRP-positive patients compared to the control subjects and the CRP-negative patients. Overexpression of these cytokines may therefore induce a hypermetabolic status that may be a cause of malnutrition and cancer cachexia.

Blood Cell Count↗
PubMed2000

The growth hormone and insulin-like growth factor 1 axis in heart failure.

Experimental data suggests that growth hormone and IGF-1 have beneficial effects on myocardial function in animal models of heart failure. Preliminary evidence suggests an abnormality in the growth hormone-IGF-1 axis in heart failure with relative growth hormone resistance. Beneficial effects of growth hormone and IGF-1 include vasodilatation, stimulation of cardiac hypertrophy, increase in calcium sensitivity of cardiac myofilaments and prevention of apoptosis. Recently, cardiac cachexia has been shown to be a powerful negative predictive factor in heart failure. Cachectic patients have higher angiotensin II levels. In the rat there is an important interaction between the renin-angiotensin system and IGF-1. Thus, angiotensin II infusion causes weight loss in part through a catabolic effect. This effect results from increased protein degradation. Angiotensin II reduces circulating and skeletal muscle IGF-1 but increases IGF-1 and the IGF-IR expression in cardiac muscle. Preliminary data suggest a potential beneficial effect of growth hormone in heart failure. Further trials are necessary to test the potential beneficial effect of growth hormone and/or IGF-1 in heart failure.

Animals↗
PubMed2000

[Clinical relevance of myosin isoforms in the diaphragm].

The diaphragm as a striated muscle is characterized by the repetition of a single element arranged in series: the sarcomere containing two kinds of myofilaments: a thick one constituted by the myosin, and a thin one primarily composed of actin. The myosin molecule consists of two heads where two myosin heavy chains (MHC) are fixed, a flexible hinge with two light (MLC) chains, and long rod-shaped tails. The diaphragm contains 4 MHC isoforms (MHC-slow, MHC-2A, MHC-2B, MHC-2X) and 6 MLC isoforms (MLC-1f, MLC-3f, MLC-1sa, MLC-1sb, MLC-2f, MLC-2s/v). In humans, the diaphragm contains mainly fibers expressing the isoforms MHC-slow, MHC-2A, and MLC-2f, MLC-2s et MLC-1f. For the mechanical properties of the different isoforms, there is a gradient from the MHC-slow to the MHC-2A, MHC-2B and MHC-2X/2B. According to the circumstances, the diaphragm will adapt towards a slow profile (COPD, cardiac failure and in animals: Duchenne muscular dystrophy, denervation-1 week, age-female, corticosteroids, chronic stimulation), or a fast profile (in animals: chronic hypoxia, denervation-2 weeks, age-males) or a more oxidative profile (in animals: cachexia, obesity). The reasons why the diaphragm adapts towards a slower or a faster muscle are not known. In fact, for a given pathological situation, several factors are able to influence the fiber composition of the diaphragm. Therefore, the net result of the influence of these different factors in terms of MHC and MLC diaphragm adaptation is difficult to predict.

Adaptation, Physiological↗
PubMed1998

Energy expenditure in Alzheimer's disease.

Alzheimer's disease type dementia is a growing health problem and is one of the leading causes of death among elderly people. Unexplained weight loss and cachexia is a frequent clinical finding in patients with Alzheimer's disease. It has been postulated that Alzheimer's disease may by characterized by dysfunction in body weight regulation. This brief review examines energy intake, energy expenditure and body composition in Alzheimer's disease. We consider whether inappropriately high levels of energy expenditure may contribute to unexplained weight loss and decline in nutritional status. Specifically, we will consider studies that have examined body composition, daily energy expenditure and its components. The application of doubly labeled water and indirect calorimetry to problems of "wasting" has increased our knowledge regarding energy expenditure and physical activity levels in Alzheimer's patients. Although the number of studies are limited, results do not support the notion that a "hypermetabolic" state contributes to unexplained weight loss in Alzheimer's disease, even in cachectic patients. Clinical strategies aimed at developing feeding strategies to maintain adequate caloric intake and the restoration of energy balance should be a future area of investigation in Alzheimer's research.

Alzheimer Disease↗
PubMed1975

Non-digestive functions of the intestinal hormones (enterines). New data and hypotheses based on experimental duodenectomy (Short review).

In cats and dogs, total duodenectomy with transplantation of the papilla Vateri into the jejunum and gastroenteroanastomosis has been shown to result in the so-called "duodenal deficiency syndrome" which is characterized, in the first phase, by cachexia of the animals occurring within 6 weeks after operation followed by obesity in the second phase. In contrast, animals with preserved by isolated duodenum do not exhibit pronounced changes in body weight as compared to intact controls. Consequently, it is suggested that intestinal hormones (enterines) not only exert gastrointestinal effects but also systemic ones. Thus, duodenectomy has been shown to lead to disturbances of lipid and protein metabolism, decreased secretory activities of the thyroid gland and the hypothalamus. Due to these findings, -- in addition to the even well-known intestinal hormones -- the existence of enterines with thyrotropic, lipotropic, hypothalamotropic, and appetite-regulating functions can be assumed which may make the duodenum act as an "abdominal hypophysis".

Ampulla of Vater↗
PubMed1975

N-nitrosomethylurea as mammary gland carcinogen in rats.

N-nitrosomethylurea (NMU) given intravenously to rats at age 50 days induced mammary carcinomas in 89% of BUF/N, 73% of Sprague-Dawley, and 89% of F344 females. Latent periods were, respectively, 77, 86, and 94 days. Mortality was negligible. Biologic properties of NMU-induced tumors were tested in the BUF/N inbred strain. Before treatment, it reduced the number of tumors per rat but not the incidence; and after the tumor was established, castration arrested tumor growth or caused a temporary regression of the tumor. Metastases to bone marrow and spleen were constant, but they were rare to the liver and lungs. After the primary tumor was removed, metastases continued to grow but at a slower rate than the growth of the primary tumor. Almost all tumors were transplantable intraperitoneally and/or subcutaneously in the inguinal area of intact as well as ovariectomized and adrenalectomized rats. Transplanted tumors were able to metastasize as were primary tumors. Doubling times of NMU-induced primary and transplanted carcinomas were similar to 7 days. Cachexia ensued at the 5th week from the onset of the first tumor. When the tumor was larger than 15 g, hypercalcemia was usually observed. The treatment described appears to be the simplest method for inducing in rats a most nearly complete model for human mammary carcinomas.

Adenocarcinoma↗
PubMed2000

[Wasting and postoperative infection in cancer patients].

Denutrition decreases immunological responses of non-cancer patients, the healing is altered whereas infectious complications increase. Now during hospitalization, malnutrition prevails in cancer patients. The suppression of the adaptability to fasting which reduces the expenditure of energy at rest, an a normal metabolic response to nutrients' supply with the impossibility to compensate totally the metabolic deficits with the artificial nutrition alone, raise the fear of postoperative disorders, particularly an increase of the infectious risk. The key point is therefore to identify the cachexia's degree owing to a simple, predictive and consensual index. This check-up allows a postoperative complications' prevention by starting up a perioperative refeeding in high-risk subjects: that is to say all severe wasting patients, the people booked for a severe surgical procedure, especially for oesophageal and gastric neoplasms. Actually, we consider that the quality of the results depend more on the making up of the different nutritional solutions dispensed than to strictly providing for cancer patients' wants, which could be harmful in the postoperative period. Supplementation with antioxidant micronutrients or arginine, glutamine, ribonucleic acids and omega-3 fatty acids would allow an immuno- modulation of the renutrition. But complications strictly due to preoperative denutrition are still to be established.

Cachexia↗
PubMedDate not supplied

Palliative care education and training during residency: a survey among residents at a tertiary care hospital.

BACKGROUND: Palliative care is the active total care of patients in advanced and incurable stages of cancer. More than 70% of all cancer patients in India require palliative care for relief of pain, other symptoms and psychosocial distress. The need for education and training in palliative care has been emphasized by the World Health Organization (WHO) during the past 15 years. This survey aimed to assess the awareness, clinical knowledge, and education and training aspects of palliative care among the clinical residents of a tertiary care hospital. METHODS: During January and February 1999, a total of 100 residents were asked to respond to a questionnaire on palliative care education and training during residency. The questionnaire consisted of 10 questions (each question with 3 different responses). Awareness regarding palliative care was assessed by 3 questions; clinical knowledge by 4 questions; and education and training obtained during residency by 3 questions. Comparisons were made using the Chi-square test between the oncology and non-oncology resident groups. RESULTS: Forty-nine residents (23 oncology and 26 non-oncology) responded to the survey. Awareness that palliative care involves active total care was lacking in 8 (16%) residents. The cost of palliative care in India was considered high by 17 (65%) non-oncology residents and 21 (43%) of the whole group. Hospice, as the right place for palliative care, was chosen by 14 (61%) oncology and 3 (11.5%) non-oncology residents (p = 0.0003). In the whole group, 21 (43%) believed that palliative care could be provided on an outpatient basis. Pain, depression and cachexia were identified as the most distressing symptoms of patients with incurable cancer. Seventeen (83%) oncology and 4 (15%) non-oncology residents (p = 0.000) knew how to use the WHO step-ladder for cancer pain relief. All oncology residents and 10 (38%) non-oncology residents preferred the oral route for providing medications for pain relief (p = 0.0001). The didactic education and training imparted during residency was considered as 'not enough' by 39% of oncology and 62% of non-oncology residents (51% overall). The confidence to deliver quality palliative care was lacking in 43% and 58% of oncology and non-oncology residents, respectively. CONCLUSION: Clinicians in India need to be provided focused skills and training for them to be able deliver quality palliative care to the large number of patients with incurable cancer. The cost of palliative care and the optimum place to deliver it, the symptoms of advanced cancer, pain relief and symptom control methods and quality of life in end-stage cancer patients are some aspects that should be an integral part of clinical residency programmes.

Cachexia↗