Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Profound weight loss and progressive depletion of muscle mass is a common sequela of chronic diseases such as cancer, tuberculosis, and human immunodeficiency virus (HIV) infection. Studies of HIV-associated wasting have revealed several possible mechanisms. Alterations in anabolic hormones, energy intake, energy expenditure, and production of proinflammatory cytokines, which cause cachexia, may contribute to wasting in HIV-infected patients. These studies have revealed the complexity of the interactions between cytokines and the hormones that typically regulate catabolic-anabolic homeostasis. Despite this complexity, HIV-associated wasting should be manageable. Several strategies are currently under investigation, including anabolic steroid and human growth hormone therapy, appetite stimulants, nutritional supplementation, and cytokine antagonists. Some of these approaches have shown early promise. Further research in these areas should facilitate development of effective intervention strategies and lead to improvements in quality of life for patients suffering from wasting syndromes.
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PMID:Human immunodeficiency virus-associated wasting and mechanisms of cachexia associated with inflammation. 948 43

Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) have a prominent role in the pathogenesis of anorexia and cachexia of chronic disease. Pentoxyfylline and thalidomide are inhibitors of TNF-alpha that have been tried as rational therapeutic interventions in cachexia. Preliminary studies with pentoxyfylline have not shown efficacy in reversing weight loss, despite evidence of TNF-alpha inhibition. In contrast, the administration of thalidomide to patients with human immunodeficiency virus- and/or tuberculosis-associated weight loss has consistently resulted in weight gain. However, the relationship of the metabolic benefits of thalidomide treatment to its complex effects on the immune system is imperfectly understood. Studies of thalidomide, either alone or in combination with other therapies for the treatment of cancer cachexia, are warranted.
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PMID:Anticytokine approaches to the treatment of anorexia and cachexia. 962 84

The major acquired immunodeficiency syndrome (AIDS) clinical trials groups in the Division of AIDS of the National Institutes of Health have been investigating weight loss and wasting in persons with the human immunodeficiency virus (HIV) and AIDS. Both the AIDS Clinical Trials Group (ACTG) and the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) have developed research projects to study the pathogenesis, diagnosis, prevention, and treatment of HIV-related malnutrition and wasting. This article reviews multicenter trials concerning HIV-related malnutrition and wasting conducted by the AIDS clinical trials groups. CPCRA trials will examine the effects of caloric supplements and triglycerides, or the use of megestrol acetate, oxandrolone, and progressive resistance training, on weight loss in patients with HIV-associated wasting. Planned ACTG trials will study the effects of the combination of megestrol acetate and testosterone, the testosterone derivative nandrolone decanoate, or highly active antiretroviral therapy on weight loss. Results from these studies may also have relevance to clinical oncologists who are treating patients with cancer-related cachexia.
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PMID:Clinical trials update in human immunodeficiency virus wasting. 962 92

A common feature of human immunodeficiency virus (HIV) infection and aging is the loss of skeletal muscle mass. Although the causes of this loss of muscle are multifactorial, there may be some shared characteristics to this loss, and therefore common strategies for its prevention or reversal. For example, loss of muscle mass early in life and early in the progression of HIV infection may result from decreased levels of physical activity. The rapid loss of skeletal muscle mass at the end of life (sometimes referred to as failure to thrive syndrome) and in acquired immunodeficiency syndrome (AIDS) patients may also have common cause: cachexia. However, it also must be pointed out that loss of skeletal muscle mass with advancing age also may result from losses of motor units, decreased rate of skeletal muscle protein synthesis, and impaired regulation of appetite. These factors have not been demonstrated to be consequences of HIV infection. The use of exercise to treat the losses of muscle size, strength, and functional capacity holds great promise. Although the losses of muscle with HIV infection may be more rapid and dramatic than those seen with aging, resistance exercise training can attenuate or arrest this loss. In elderly people, resistance exercise has been demonstrated to result in increased nitrogen balance, muscle mass and strength, functional capacity, energy requirements, and when combined with a protein calorie supplement, increased energy intake. The use of resistance exercise in HIV-infected patients may also provide similar results. This review discusses many of the changes in body composition, physiological function, and metabolism associated with aging and HIV infection. The specific effects of exercise in the elderly and in patients infected with HIV on the treatment of muscle wasting, and its consequences are also discussed.
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PMID:Exercise and the treatment of wasting: aging and human immunodeficiency virus infection. 962 93

Rifabutin pharmacokinetics were studied by the population approach (NONMEM) with 40 human immunodeficiency virus-infected patients receiving rifabutin at different doses for prophylaxis or therapy of mycobacterial infections. A two-compartment open model with first-order absorption was used as the structural pharmacokinetic model. Parameter estimates were the absorption rate constant (0. 201/h), clearance/bioavailability (CL/F; 60.9 liters/h), volume of the central compartment/bioavailability (231 liters), intercompartmental clearance (60.3 liters/h), and volume of the peripheral compartment/bioavailability (Vp/F; 1,050 liters). The distribution and elimination half-lives were 1.24 and 25.4 h, respectively. The covariates tested for influence on CL/F and Vp/F were sex, age, weight, height, body surface area, tobacco smoking, drug addiction, alanine aminotransferase levels, creatinine clearance, total protein, bilirubin, numbers of CD4(+) cells, presence of diarrhea, cachexia index, rifabutin use (prophylaxis versus therapy), rifabutin dose, study site, and the concomitant administration of clarithromycin, fluconazole, phenobarbital, ciprofloxacin, azithromycin, or benzodiazepines. The only statistically significant effects on rifabutin pharmacokinetic parameters were a 27% decrease in Vp/F due to the concomitant administration of azithromycin and a 39% increase in Vp/F due to tobacco smoking. Such effects may be considered clinically unimportant. Our results confirm the lack of a correlation of rifabutin pharmacokinetic parameters with parameters of disease progression and gastrointestinal function. Also, the lack of a correlation with covariates which were previously found to be significant, such as concomitant fluconazole and clarithromycin use, may suggest that the effect of such covariates may be less important in the real clinical setting, in which several concomitant factors may influence pharmacokinetic parameters, with an overall effect of no apparent correlation.
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PMID:Population pharmacokinetics of rifabutin in human immunodeficiency virus-infected patients. 968

We developed a model of cancer cachexia by transplanting VX2 tumors into rabbits and investigated the effects of plasmapheresis in this model. AIS activity was identified in supernatants obtained from VX2 tumor by phenyl Sepharose chromatography. Fractions eluted with 0.5 M NaCl showed the ability to damage the red blood cell membrane and suppress immunity. Rabbits exhibited marked weight loss, anemia and immunodeficiency 40 days after transplantation of VX2 tumors. Plasmapheresis inhibited plasma-induced damage of the red blood cell membrane and suppression of immunity. Twice-weekly plasmapheresis resulted in gradual normalization of cellular immunity. Weight loss and survival were also improved. No side effects were observed.
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PMID:Effects of plasmapheresis in a rabbit model of cancer cachexia. 983 15

The present article reviews immune ageing and its relationship with nutritional ageing, with a particular insight into the influences of disease on both ageing processes. Immune ageing can be described primarily as the progressive appearance of immune dysregulations, mainly acquired immunity (mature: immature, naive: memory T lymphocyte subset decreases) leading to gradual increases in T-helper 2: T-helper 1 cells. This change is due initially to decreased thymic function, and later to accumulative antigen pressure over the lifespan. In contrast, innate immunity (macrophage functions) is preserved during the ageing process and in the elderly this leads to macrophage-lymphocyte dysequilibrium, which is particularly critical during on-going disease. Indeed, any disease induces long-lasting acute-phase reactions in aged patients and leads to body nutritional reserve (mainly protein) losses. Episodes of disease in the aged patient progressively deplete body nutritional reserves and lead to protein-energy malnutrition, undernutrition-associated immunodeficiency, and finally cachexia. Undernutrition is a common symptom in the elderly; protein-energy malnutrition is found in more than 50% of hospitalized elderly patients and in most elderly diseased subjects. In addition, micronutrient deficit or low levels are common in home-living self-sufficient apparently-healthy elderly subjects. All these nutritional deficits induce decreased immune responses, and micronutrient deficits are now thought to be partly responsible for the decreased immune responses (immune ageing?) observed in the apparently-healthy elderly. Indeed, several studies have shown that micronutrient supplements induce increased immune responses in the healthy elderly. The progression of infectious diseases depends on immune responses and on nutritional status before the onset of illness in aged subjects. In addition, recovery depends on the intensity of acute-phase responses in the undernourished elderly. In fact, chronic acute-phase responses, commonly associated with diseases in aged patients, lead to progressive lowering of metabolic responses in the undernourished elderly. This can be quantified by increased production of free radicals during treatment and these increases may explain the difficulty in successfully treating aged patients. Nutritive therapy in order to improve metabolic processes and also to maintain body reserves should be considered as a necessary adjuvant therapy in the treatment of elderly patients.
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PMID:Immune response during disease and recovery in the elderly. 1034 45

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.
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PMID:Elimination of anemia-inducing substance by cyclic plasma perfusion of tumor-bearing rabbits. 1049 46

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.
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PMID:Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases. 1064 95

The association between pharmacologic doses of corticosteroids and the development of aseptic bone necrosis has been well documented. Recent reports have described the corticosteroid activity of megestrol acetate. A retrospective review of adverse events reported to the U.S. Food and Drug Administration identified three human immunodeficiency virus (HIV) seropositive patients who developed avascular necrosis of the femoral head during treatment with megestrol acetate. All were males, ages 34, 36, and 55 years, and were on therapy for 6, 1.5, and 18 months, respectively, when symptoms of aseptic necrosis occurred in the absence of antecedent trauma. Megestrol acetate doses were 640, 320, and 600-1200 mg/d, respectively. Two patients had no history of corticosteroid use whereas the third had taken an undisclosed dose and duration of corticosteroids concurrent with pentamidine administration. Notably, despite the predominant use of megestrol in women for hormone sensitive malignancies, none of the reports of aseptic necrosis occurred in this population. Megestrol acetate may be associated with the development of avascular necrosis via its glucocorticoid-like effects. Cachectic acquired immunodeficiency syndrome (AIDS) patients may have additional risk factors that predispose them to aseptic necrosis when receiving megestrol acetate.
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PMID:Aseptic necrosis in HIV seropositive patients: a possible etiologic role for megestrol acetate. 1097 69


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