Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical presentation of visceral leishmaniasis, or kala-azar, is variable but usually includes fever, severe cachexia, lymphadenopathy and hepatosplenomegaly. In immunocompromised patients the clinical course of the disease is even less specific and the diagnosis is often made by means of incidental detection of the parasites at atypical sites such as the gastrointestinal tract, peripheral blood, lungs and cerebrospinal fluid. We describe a case of pericardial leishmaniasis in an HIV-infected patient.
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PMID:Visceral leishmaniasis with pericarditis in an HIV-infected patient. 1192 56

Although catastrophic weight loss is no longer common in HIV-infected men, we hypothesized that a more gradual process of cachexia [loss of lean body mass (LBM) without severe weight loss, often accompanied by elevated resting energy expenditure (REE)] is still common and is driven by excessive production of the catabolic cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). We performed a longitudinal analysis of an ongoing cohort study of nutritional status in 172 men with HIV infection. LBM loss of >1 kg occurred in 35% of the cohort, and LBM loss of >5% occurred in 12.2% over 8 mo of observation, but classical wasting (loss of approximately 10% of weight) was rare (2%). Both TNF-alpha (-150 g LBM. ng(-1) x ml(-1), P < 0.02) and IL-1 beta production (-130 g LBM x ng(-1) x ml(-1), P < 0.01) by peripheral blood mononuclear cells predicted loss of LBM. A rise in REE of >200 kcal/day was found in 17.7% of the subjects regardless of weight change. IL-1 beta (+9 kcal/day per ng/ml, P < 0.002) and TNF-alpha (+10 kcal/day per ng/ml, P < 0.02) production predicted Delta REE. Serum free testosterone was inversely associated with TNF-alpha production and was not an independent predictor of either Delta LBM or Delta REE after adjustment for cytokine production. Even though weight loss was rare in this cohort of patients treated with highly active antiretroviral therapy, loss of LBM was common and was driven by catabolic cytokines and not by inadequate dietary intake or hypogonadism.
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PMID:Role of cytokines and testosterone in regulating lean body mass and resting energy expenditure in HIV-infected men. 1206 54

Wasting, and particularly loss of metabolically active lean tissue, contributes to increased mortality, accelerated disease progression, and impairment of strength and functional status in patients with HIV infection. A variety of protein anabolic agents, including growth hormone, insulin-like growth factor-I, testosterone, nandrolone decanoate, oxandrolone, and oxymetholone, have been studied in patients with HIV-associated wasting. Overall, these studies have demonstrated that treatment with protein anabolic agents can increase lean body mass (LBM) and in some cases provide functional benefits and improvements in quality of life. Further research is needed to determine whether such treatment prolongs survival or reduces the overall health care burden of HIV infection. The advances in identification of successful treatments for HIV-associated wasting can provide a model for using these therapies in other catabolic states, including end-stage renal disease, cancer, chronic obstructive pulmonary disease, and cardiac cachexia.
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PMID:Anabolic treatment with GH, IGF-I, or anabolic steroids in patients with HIV-associated wasting. 1216 20

Thalidomide, administered as a sedative and antiemetic decades ago, was considered responsible for numerous devastating cases of birth defects and consequently was banned from markets worldwide. However, the drug remarkably has resurfaced with promise of immunomodulatory benefit in a wide array of immunologic disorders for which available treatments were limited. It is approved by the Food and Drug Administration for erythema nodosum leprosum (ENL). Although the relative paucity of leprosy and ENL worldwide may perceivably limit interest in and knowledge about thalidomide, increasing numbers of new and potential uses expand its applicability widely beyond ENL. Thalidomide, an inhibitor of tumor necrosis factor a, is the best known agent for short-term treatment of ENL skin manifestations, as well as postremission maintenance therapy to prevent recurrence. For this indication, it is effective as monotherapy and as part of combination therapy with corticosteroids. Studies of thalidomide in chronic graft-versus-host disease showed benefit in children and adults as treatment, but not as prophylaxis. The agent has been administered successfully for treatment of cachexia related to cancer, tuberculosis, and human immunodeficiency virus infection, although evidence of efficacy is inconclusive. Thalidomide monotherapy effectively induced objective response in trials in patients with both newly diagnosed and advanced or refractory multiple myeloma. Combination therapy with thalidomide and corticosteroids was also effective in these patients, as well as in treatment of aphthous and genital ulcers. Limited evidence supports the drug's benefit in treatment of Kaposi's sarcoma. Other thalidomide applications include Crohn's disease, rheumatoid arthritis, and multiple sclerosis. Somnolence, constipation, and rash were the most frequently cited adverse effects in studies, but thalidomide-induced neuropathy and idiopathic thromboembolism were critical causes for drug discontinuation. Thalidomide is still contraindicated in pregnant women, women of childbearing age, and sexually active men not using contraception. Clinicians should be conversant with thalidomide in ENL (its primary application) in the natural course of leprosy, as well as in the agent's other applications.
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PMID:Thalidomide for erythema nodosum leprosum and other applications. 1268 Apr 78

Advanced Viral Research Corp is developing reticulose, a nontoxic peptide nucleic acid preparation, for the potential treatment of viral infection. The compound is undergoing phase II clinical trials for the potential topical treatment of human papillomavirus infection in the US. Reticulose has also been investigated in clinical studies for the treatment of HIV infection in Barbados. Additionally, the drug is being investigated for the potential treatment of adenovirus infection, and is being evaluated in adjuvant arthritis models by the Weizmann Institute of Science. Investigations into the use of reticulose to reduce the toxic effects of cancer treatment are underway in Israel. Phase I trials in patients with cachexia associated with HIV, lymphoma and solid tumor, have also been initiated in Israel.
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PMID:Technology evaluation: reticulose, advanced viral research. 1277 10

AIDS-associated Kaposi's sarcoma (AIDS-KS) represents one of the most common malignancies associated with human immunodeficiency virus infection. To target effective therapeutic agents, we have discovered that AIDS-KS cells express high-affinity receptors for interleukin-4 (IL-4), a pleiotropic immune regulatory cytokine. Molecular studies have revealed that AIDS-KS cells express type II IL-4 receptors, in which IL-4 forms a productive complex with primary IL-4 binding protein (IL-4R beta, also known as IL-4R alpha) and a shared subunit between IL-4 and IL-13R systems (IL-13R alpha', also known as IL-13R alpha 1). A recombinant fusion protein composed of IL-4 and a mutated form of a powerful bacterial toxin called Pseudomonas exotoxin (PE)--the fusion protein is termed IL4(3837)-PE38KDEL or cpIL4-PE--was found to be highly and specifically cytotoxic to AIDS-KS cells in vitro. Normal human immune cells (e.g., resting T and B cells and monocytes) or endothelial cells, a possible precursor of AIDS-KS, expressed low numbers of IL-4R and showed little or no sensitivity to cpIL4-PE. Administration of cpIL4-PE in nude mice with established subcutaneously growing AIDS-KS tumors produced remarkable antitumor activity in a dose-dependent manner with the highest dose exhibiting complete responses without any visible toxicity. KS tumors produced metabolic changes including cachexia, hypoglycemia and lymphopenia, all of which were prevented by cpIL4-PE treatment. These studies indicate that cpIL4-PE is a promising experimental therapeutic agent for treatment of AIDS-KS.
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PMID:IL-4 receptor-directed cytotoxin for therapy of AIDS-associated KS tumors. 1293 11

The authors carried out a research project in a nursing consultancy on patients suffering from Human Immunodeficiency Virus. Their study comprised 108 patients. The authors analysed the causes which provoke nutritional problems since the signs and symptoms derived from this disease are associated with opportunistic infections which directly affect nutritional requirements. The authors selected variables which would determine general parameters for a nutritional study: anthropological measurement parameters such as weight, height and other basic vital measurements; Biochemical parameters such as albumin and ferritin; clinical parameters such as diarrhoea, vomiting, anorexia, fever, and dysphagia. The biochemical parameters provided evidence in the albumin measurements that 65.28% of these patients suffer from severe malnutrition. With regards to anthropological measurements, basic vitals showed that 16.8 of these patients have a normal range while 52.64% fall below the 10th percentile which demonstrate important levels of cachexia. In the near future, these authors shall publish their study regarding the eating habits of these patients and its relationship to their nutritional status.
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PMID:[Nutrition in HIV patients]. 1450 91

Currently there are no effective orally administered drugs or visceral leishmaniasis or kala-azar, a parasitic disease affecting about 0.5 million people a year, majority of whom are in India and adjacent areas of Nepal. Symptoms of affected patients are fever, cachexia, hepatosplenomegaly and pancytopenia. The disease is usually fatal, if left untreated. Traditionally kala-azar is treated with four weeks of injections of sodium stibogluconate, a pentavalent antimonial. However, this treatment has not only shown resistance in 37-64% patients of the current Indian epidemic in Bihar (the epicentrre) but also life-threatening cardiotoxicity in 7-10% and treatment-related deaths in 5-10% cases, besides being unsuccessful at times. Parenteral amphotericin B is used as a secondary agent that shows 95% effectiveness but its toxicity and high cost of even the well tolerated liposomal complex precludes its wide use in the developing countries, where the disease is present in epidemic proportions. Recently, miltefosine (hexadecylphosphocholine), a compound originally developed as an antitumour agent has been shown to be an orally effective drugs against kala-azar. All clinical trials with this drug are conducted in India in patients of visceral leishmaniasis. A regimen of 100 mg per day or 50 mg twice daily for 3-4 weeks was observed to produce a cure rate of 100%. Gastrointestinal side effects were frequent (62%) but no patient discontinued the therapy. A phase III trial involving 300 HIV-negative adults and adolescents is underway in India and the drug is hoped to be licensed in the next 2-3 years. Few studies of phase II clinical trials mainly conducted in Kenya with another drug, sitamaquine or kalazaquine (WR 6026), an 8-aminoquinoline has also shown promise as an orally effective agent (in a dose of 1 mg/kg/day for two weeks) for visceral leishmaniasis. These Studies with two orally effective compounds, it appears, will open new vistas for orally effective, affordable and acceptable drugs in the armamentarium for the treatment of kala-azar. It is expected that in future we would have effective ways to prevent and treat all forms of leishmaniasis without discomforting the patient.
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PMID:Orally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine. 1462 Oct 30

The oral traditions of medicine and public health have it that malnutrition is an important risk factor for the development of tuberculosis (TB). Malnutrition profoundly affects cell-mediated immunity (CMI), and CMI is the principle host defense against TB. It makes biological sense. Although most health professionals readily accept this principle, much of this belief is based on uncontrolled observations such as disaster situations or on backwards logic from the cachexia common among TB patients. In fact, the evidence in humans is surprisingly thin from the perspective of scientific rigor. And few data, if any, quantify the extent of the relative or attributable risk of TB due to malnutrition. Moreover, until recently, data from experimental animals were based on animal models that were largely not relevant to human TB infection and disease. This article reviews the scientific data supporting the contention that malnutrition is an important risk factor for TB concentrating on observations in humans and on experimental animal studies based on a highly relevant animal model. If it is true, malnutrition may account for a greater population attributable risk of TB than HIV infection, and certainly a much more correctable one.
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PMID:The relationship between malnutrition and tuberculosis: evidence from studies in humans and experimental animals. 1513 64

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.
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PMID:The promise of thalidomide: evolving indications. 1514 28


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