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)

Cachexia is a common problem in persons infected with the human immunodeficiency virus (HIV). Megestrol acetate, an agent used for the treatment of metastatic breast cancer, is associated with appetite stimulation and weight gain. To determine whether this drug might benefit HIV-positive patients, 22 such subjects (14 previously reported) were treated with oral megestrol acetate, beginning at a dose of 80 mg four times daily. All patients had lost at least 10% of their preillness weight prior to treatment; the median loss was 11.4 kg (range, 5.5 to 26.8). Preliminary data from patients observed during therapy from 2 to 72 weeks showed that 21 of the 22 patients gained weight; the average weight gain was 7.3 kg (range, -4.1 to 17.3). Three patients failed to gain weight on 320 mg per day of megestrol acetate; both appetite stimulation and weight gain were achieved with 460 mg per day in one and 640 mg per day in another. One patient continued to lose weight despite 480 mg per day megestrol acetate. The median time to peak weight during megestrol acetate treatment was 14 weeks. Seven patients returned to within 1 kg of their normal body weight. In three of the 22 patients treated, megestrol acetate and zidovudine were started simultaneously. For these three patients, weight gain was potentially due to the recognized weight gain associated with the initiation of zidovudine. For the remaining 18 patients, however, appetite stimulation and weight gain were a result of megestrol acetate. All patients tolerated the drug well. One patient developed a deep vein thrombosis. No patient developed peripheral edema or drug-related impotence. The appetite improvement and weight gain seen in this initial series are encouraging. The true effectiveness of megestrol acetate for HIV-related cachexia and the effects of treatment on quality of life are currently being assessed in a national prospective, randomized, double-blind, placebo-controlled trial.
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PMID:Megestrol acetate for treatment of anorexia and cachexia associated with human immunodeficiency virus infection. 225 23

A guiding objective of phase III clinical trials should be to achieve reliable evaluation of safety and efficacy of interventions in a real-world setting, ie, as the interventions would be delivered in clinical practice. This guiding objective motivates several principles of design. The control regimen should truly reflect standard of care; in turn, one should be reluctant to use placebos that might not be inert or that might adversely impact quality of life. The choice of concomitant therapy should be sufficiently flexible as to allow for treatment options that would be widely representative of routine care. Eligibility criteria should be as inclusive as the intended labeling, specifically excluding only those patients expected to be at high risk for toxicity or have a low likelihood of benefit. Study procedures should be simplified to avoid unnecessary inconvenience to patients and investigators and to reduce trial costs. Clinical end points should be chosen that unequivocally reflect tangible benefit to patients. Experiences from the phase III trial of trastuzumab (Herceptin; Genentech, San Francisco, CA) in metastatic breast cancer, a human immunodeficiency virus/acquired immunodeficiency syndrome trial, and a trial in cardiology will be used to provide additional motivation for several of these principles. These trials provide valuable insights into the challenging issues arising in the design and conduct of clinical trials.
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PMID:Issues in the design of clinical trials: insights from the trastuzumab (Herceptin) experience. 1048 1

Pyomyositis is a rare complication of chemotherapy. A 47-year-old woman with metastatic breast cancer, in whom pyomyositis developed after chemotherapy, is described. It was difficult to differentiate between pyomyositis and deep venous thrombosis early in her admission. Pyomyositis should be considered part of the differential diagnosis of deep venous thrombosis. This infection, after chemotherapy, usually is considered to be caused by neutropenia or immunodeficiency secondary to the cancer, or both. It is postulated that subclinical myopathy, secondary to the malignancy or drugs used in treating the malignancy, or both, may also predispose to pyomyositis.
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PMID:Pyomyositis after chemotherapy for breast cancer. 1068 75

The rising incidence of the human immunodeficiency virus (HIV) infection in women and the prolonged survival increases the risk of development of breast cancer in this population. Through December 2001, 38 cases of breast cancer, two occurring in men, have been reported in persons infected with HIV. Between 1995 and 2001, five HIV infected premenopausal women presented with breast cancer to the Karmanos Cancer Institute. Three patients presented 3-5 years after the diagnosis of HIV infection. One patient presented with stage IV breast cancer, three with stage III, and one with stage II disease. Chemotherapy-induced myelosuppression was pronounced in all patients. Two patients had progression of HIV on treatment manifested by a rise in HIV-1 RNA or development of opportunistic infections. In general, the outcome of breast cancer in our small series of patients was worse than in a non-HIV population. HIV infection may influence the natural history and treatment of breast cancer.
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PMID:Breast cancer in women with human immunodeficiency virus infection: implications for diagnosis and therapy. 1245 47

Megestrol acetate is a progestational agent for treatment of metastatic breast cancer and endometrial cancer. Megestrol has also been used as an appetite stimulant for patients with human immunodeficiency virus and malignancy who experience cachexia and wasting; also, megestrol can be beneficial in relieving hot flashes in women and men. Megestrol has been shown to have a glucocorticoidlike effect and has been associated with substantial suppression of plasma estradiol levels. We describe 2 patients who recently presented to our Metabolic Bone Disease Clinic with severe osteoporosis complicated by multiple vertebral fractures experienced while the patients were receiving high-dose megestrol therapy. The patients had evidence of adrenal axis suppression but recovered fully after megestrol was discontinued. We speculate that megestrol was an important factor in the development of osteoporosis and subsequent fractures. Further study is warranted to clarify the relationship between megestrol and its potential for adversely affecting the skeleton.
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PMID:Osteoporosis associated with megestrol acetate. 1559 41

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c+) and plasmacytoid (CD123+) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR(+)IC). Although DR(+)IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR(+)IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR(+)IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR(+)IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR(+)IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.
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PMID:A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer. 1635 94

Megestrol acetate (MA) is a progestational agent for the treatment of metastatic breast cancer and endometrial cancer. MA has also been used to promote weight gain in malnourished elderly patients, in patients with immunodeficiency virus and in cancer-induced cachexia. In addition to thromboembolic disease, MA may induce hyperglycaemia, osteoporosis, suppression of the gonadal axis, and Cushing's syndrome. MA has also been shown to cause symptomatic suppression of the hypothalamic-pituitary-adrenal (HPA) axis owing to its intrinsic glucocorticoid-like effect. Three additional patients are presented who developed symptomatic adrenal insufficiency while they were receiving 160-320 mg MA daily. The patients were treated with cortisone acetate supplements, had clear evidence of HPA-axis suppression but recovered fully after MA was discontinued. Patients receiving MA might have an inadequate adrenal response during stressful conditions, possibly because 160-320 mg MA daily may not provide adequate protection to prevent the symptoms of adrenal insufficiency. The adverse MA effect on the HPA axis is probably not well recognised in clinical practice, and clinicians need an increased awareness of the endocrine complications secondary to MA treatment.
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PMID:Primary symptomatic adrenal insufficiency induced by megestrol acetate. 2341 18

In view of the fact that insufficiency in immune response often correlates with poor prognosis, research in recent years has focused on the task of describing the precise status and function of the immune system and its possible effect on cancer patients. Although more than two thirds of treated patients respond to endocrine therapy, most patients with metastatic breast cancer develop a resistance to it. Estrogen modulates angiogenesis, partially through its effects on vascular endothelial growth factor (VEGF). It also appears that transforming growth factor-beta (TGF beta) could be another factor contributing to this resistance. TGF beta is a highly immunosuppressive factor that inhibits natural and specific immunity against tumors and stimulates the production of VEGF. The purpose of the study was to monitor immune responses in patients with hormone receptor-positive breast cancer who were resistant to hormone therapy. The examination of cellular components (CD4, CD8, HLA-DR, NK cells) and humoral immunity (IgG, IgG subclasses, IgA, IgM,). TGF beta and VEGF production were monitored with special attention, along with an analysis of the changes that occurred during the hormonal treatment. 68 patients included in the research project were implemented with routine cancer treatment with endocrine therapy. Basic parameters (the histological type and grade, the degree of expression of estrogen receptors (ER) and progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF beta and VEGF were measured by ELISA and antitumor cellular immunity (CD4, CD8) was measured by flow cytometry. Patients who failed in the first line of hormone therapy treatment were considered as resistant to hormone therapy.Depression in cellular immunity was found especially in patients with resistance to endocrine therapy. In addition, immunoglobulin plasma levels were decreased (mainly IgG4 subtype). Most patients showed clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections). Significant increases in TGF beta and VEGF plasma were also detected.The correlation of these factors with resistance to hormonal therapy and the state of anticancer immunity could be helpful in the task of predicting resistance to hormonal therapy and could contribute to the selection of targeted immune therapy in cancer patients in the future.
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PMID:Cellular and humoral immunodeficiency in breast cancer patients resistant to hormone therapy. 2419 14