Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus is an autoimmune disease of unknown cause characterized by exacerbations and remissions. Disease manifestations are diverse, but the most common symptoms are fatigue, fever, weight loss, skin rash, arthritis or arthralgias, and anemia. Clinical findings and measurement of antibody titers are the most common diagnostic criteria. Individualized therapy with corticosteroids, immunosuppressives, or antimalarial agents and careful monitoring of disease activity are essential.
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PMID:Systemic lupus erythematosus. How to manage this chronic, complicated disorder. 268 93

The characteristics and clinical uses of recombinant colony-stimulating factors (CSFs) are described, and the pharmacist's role as a consultant and educator on biotherapeutic substances is discussed. CSFs stimulate the formation and differentiation of the erythrocytes, neutrophils, eosinophils, basophils, monocytes, and platelets that compose the blood cell population. Recombinant CSFs represent a means by which the numbers of hematopoietic cells can be modulated, thus making these agents potentially useful in treating hematologic and immunologic deficiencies. CSFs also can increase the ability of neutrophils and monocyte-macrophages to protect the body against foreign invasion. Granulocyte macrophage colony-stimulating factor (GM-CSF) has increased host defenses in acquired immunodeficiency syndrome patients with Kaposi's sarcoma; increased neutrophil, platelet, and erythrocyte counts in preleukemic patients; and increased neutrophil counts in patients with aplastic anemia. GM-CSF and granulocyte colony-stimulating factor (G-CSF) have appeared to alleviate the drastic decrease in neutrophil counts associated with cytotoxic chemotherapy. G-CSF also has shown promise in stimulating neutrophil production in patients with transitional cell carcinoma, congenital agranulocytosis, and hairy-cell leukemia. Mild adverse effects such as fever, chills, rash, fatigue, myalgia, and bone pain are associated with GM-CSF therapy; G-CSF therapy is associated mostly with mild to moderate bone pain. Areas of education for pharmacists working with biotherapeutic substances include stability, storage temperature, drug interactions, novel drug-delivery systems such as monoclonal antibodies or liposomes, variations in biologic activity, and the evolving nature of the information about these investigational drugs. The pharmacist can anticipate an increasing role as a consultant on the use of CSFs and other biotherapeutic substances.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony-stimulating factors and tomorrow's pharmacy: why we must be ready. 269 Jun 7

Twenty-four evaluable patients with metastatic melanoma have been entered in a multicentre Phase II study of two induction cycles of human recombinant interleukin-2 (rIL-2) 18 x 10(6) IU/m2/day continuous i.v. bolus on days 1-5 and days 12-17. Dacarbazine (DTIC) 850 mg/m2 i.v. bolus was given on day 26. The cycle was repeated at five weeks. Maintenance therapy was scheduled three weeks after the completion of the induction treatment, consisting of rIL-2 18 x 10(6) IU/m2/day for five days alternating with DTIC 850 mg/m2 i.v., every three weeks, for a total of 18 weeks. Median age was 44 years (range 23-80), and Karnofsky index was 100 (range 80-100). One patient had received prior chemotherapy with hydroxyurea and one patient had prior radiotherapy. Six patients responded (25%): two had complete responses (CR) and four had partial responses (PR). Stable disease (SD) was seen in five patients. Responses occurred in the following sites: liver 2/9 (22%), lung 3/14 (21%), skin 2/11 (18%), and lymph nodes 3/12 (25%). Duration of CR was 11+ and 13 months. PRs lasted 2, 5, 7, and 11+ months. Of note, time to progression in patients with SD was similar to that of responders: 4, 4, 11+, 11+, and 14+ months. Toxicity included fever, skin rash, fatigue, anorexia, and diarrhoea in most patients. Two patients had a weight gain of more than 10%. Hypotension requiring vasoactive agents or interruption of rIL-2 occurred in four patients, creatinine elevations WHO grade 1-2 in seven patients, and bilirubin elevations WHO grade 1-3 in six patients. One patient developed transient ventricular tachycardia. It appears that rIL-2 and DTIC in this schedule is feasible and effective, but not clearly superior to rIL-2 alone.
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PMID:Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma. A multicentre phase II study. 269 78

High-dose interleukin-2 (IL-2) with or without lymphokine-activated killer (LAK) cells has been reported to have activity in certain solid tumors, but toxicity has usually required hospitalization for administration. The purpose of this trial was to determine the antineoplastic effect and toxicity of IL-2 administered at a lower dose in an outpatient setting. Eligibility criteria included measurable disease, Karnofsky performance greater than or equal to 70%, age greater than 18 years, and adequate bone marrow, renal, and hepatic function. The median age of 35 patients was 56 years (range, 20 to 75). Diagnoses included malignant lymphoma (ML), (nine patients), chronic lymphocytic leukemia (CLL) (eight), melanoma (eight), colorectal cancer (six), renal cancer (two), and breast cancer (two). The initial 18 patients were treated with 1 mg/m2 (3 x 10(6) U/m2 intravenous [IV] bolus) for five days every other week for a total of 4 treatment weeks (8 weeks total). The subsequent 17 patients were treated with 0.5 mg/m2 (1.5 x 10(6) U/m2). All patients were evaluable for toxicity, and 26 for tumor response. Toxicities included fatigue (71%), nausea (69%), hypotension (54%), fever (51%), chills (40%), weight gain (37%), pruritus or rash (31%), dyspnea (14%), azotemia (6%), confusion (6%), thrombocytopenia (6%), and myocardial infarction (3%). Four patients died from apparently unrelated causes within the first 2 weeks of treatment. Treatment was discontinued before the completion of 8 weeks of treatment because of progressive disease (12 patients), severe hypotension (three), azotemia (one), myocardial infarction (one), early death (four), and miscellaneous causes (two). IL-2 at 1 mg/m2 IV for five days is associated with moderate toxicity, but a dose of 0.5 mg/m2 is tolerable for outpatient administration. Three partial responses (PR) and one minor response (MR) lasting 1 to 17+ months have been observed in 12 patients with ML and CLL evaluable for response. One additional MR was observed in a patient with melanoma. IL-2 deserves further study in patients with ML and CLL.
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PMID:Phase II trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia, and selected solid tumors. 278 39

Nineteen evaluable patients with advanced malignancy were treated with recombinant methionyl human interleukin-2 (Ala 125), 5 days per week by intravenous bolus. Patients were entered in five groups at starting doses ranging from 0.05 to 2.56 x 10(6) U/m2. Doses were escalated weekly as tolerated toward a potential maximal dose of 11.6 x 10(6) U/m2. Maximal tolerated dose was 3.84 x 10(6) U/m2. Dose-limiting toxicity included fatigue, rigors, nausea/vomiting, fever, and diarrhea. Other toxicities included hyperesthesias, arthralgias/myalgias, rash, fluid retention, balanitis, and mild confusion. Leukocytosis, including granulocytosis, eosinophilia, and mild lymphocytosis, was observed, as was rare mild thrombocytopenia. No partial or complete response occurred. T1/2 alpha averaged 13.4 min, with interleukin-2 detectable 2 h after doses of greater than or equal to 2.56 x 10(6) U/m2. Three patients developed anti-IL-2 antibodies without demonstrable clinical significance.
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PMID:Systemic administration of recombinant methionyl human interleukin-2 (Ala 125) to cancer patients: clinical results. 278 63

The effectiveness of enalapril 10-40 mg/day as first choice treatment of mild (90-104 mmHg, n = 37), moderate (105-114 mmHg, n = 21), or severe (115-130 mmHg excluding accelerated hypertension, n = 16) essential hypertension was studied in an open multicentre trial. Enalapril alone controlled the hypertension (diastolic blood pressure 90 mmHg or less) in 25 patients (34%). Of these, 20 had mild and 5 had moderate hypertension. The remaining patients required either enalapril plus hydrochlorothiazide 12.5 or 25 mg/day (n = 30), or a third drug of the physician's choice (n = 9). A relationship was present between baseline blood pressure and the number of drugs required to achieve blood pressure control. Plasma creatinine increased beyond the limits of laboratory error in 3 patients, and from 100-108 mumol/l (p less than 0.05) on enalapril alone in a subgroup of patients who ultimately required a diuretic. Enalapril was well tolerated; 60 (73%) had no drug related side effects during active treatment. Tiredness (n = 5), headache (n = 4), dizziness (n = 4) and palpitations (n = 3) were the most frequent side effects. Cough was a feature in 3 patients and 1 patient had a rash. This study suggests that enalapril is an effective and well tolerated anti-hypertensive agent in mild, moderate or severe hypertension, but that caution may be required in patients with impaired renal function.
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PMID:Enalapril as first choice treatment of mild, moderate and severe essential hypertension: results of an open multicentre clinical trial. New Zealand Hypertension Study Group. 283 97

A 29 year old white homosexual man presented with a two and a half week history of severe sore throat, fever, and extreme fatigue. His symptoms did not respond to antibiotics. He had mild bilateral conjunctivitis, a rash over his chest and back, and enlarged lymph nodes, but examination of the nervous system yielded normal results. He had low total white cell and platelet counts. The results of enzyme linked immunosorbent assay for human immunodeficiency virus (HIV) were equivocal when HIV IgM was detected in serum. Despite treatment with ampicillin his temperature remained high and he developed abnormal neurological signs, including a paraparesis and hyperreflexia of the arms. HIV was isolated from lymphocytes from blood and cerebrospinal fluid. Over the next six weeks the patient improved and was discharged. Two months later abnormal neurological signs persisted in his legs. Although various neurological syndromes associated with seroconversion to HIV have been described, this is probably the first report of a patient with myelopathy at the time of seroconversion.
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PMID:Acute myelopathy associated with primary infection with human immunodeficiency virus. 288 58

One hundred twenty-eight women with advanced metastatic breast cancer were treated with a combination of aminoglutethimide (AG) (1000 mg orally, daily) and medroxyprogesterone acetate (MPA) (1500 mg orally, daily for six weeks and thereafter 500 mg orally, daily; omitting cortisone substitution). AG/MPA did not lead to side effects other than those described under AG or MPA monotherapy. Mental and personality changes seem to be more severe and frequent under combined therapy than under monotherapy. Impairment of mental functions, depressive syndromes, fatigue, ataxia, skin rash, and transient increase of gammaglutamyl transferase appeared and disappeared within the first 4 to 6 weeks of treatment. Objective remissions of at least 3 months duration from initiation of therapy were seen in 21 of 128 patients (21.9%) (3.9% complete remission [CR], 18% partial remission [PR]). A no change (NC) status occurred in an additional 25.8%. The remission duration (mean and range) was 19 (10.5-54) for CR, 16.5 (4.5-52+) for PR and 6 (3-27) months for NC patients. The highest response rate was registered for patients with only bone involvement (PR, 11; and NC, 11 of 26 patients). There was a distinct correlation of response to prior systemic treatment, receptor status of the primary tumor, disease-free interval, menopausal status, age and condition of the patient. PR was obtained in 4 of 20 patients with receptor-negative primary tumors. These results justify a prospective trial comparing AG/MPA with other forms of endocrine therapy in selected patient subgroups.
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PMID:Aminoglutethimide and medroxyprogesterone acetate in the treatment of patients with advanced breast cancer. A phase II study of the Association of Medical Oncology of the German Cancer Society (AIO). 294 73

Interleukin 2 (IL-2) therapies have antitumor activities against several neoplasms. In vitro these activities are enhanced by beta-interferon (IFN-beta). Therefore, we initiated a Phase I trial with a combination of IL-2 and IFN-beta three times weekly. The IFN-beta was administered i.v. Initially, the IL-2 was administered s.c. However, neutralizing antibody to the IL-2 developed in five patients, and the route of administration of the IL-2 was changed to i.v. Forty-seven patients were entered on the study. The maximum tolerated doses for the combination given i.v. were 5 x 10(6) units/m2 of IL-2 and 10 x 10(6) units/m2 of IFN-beta. Dose-limiting toxicities were profound fatigue/decreased performance status, anorexia/weight loss, depression, and arthralgias. Hypotension, exfoliative skin rash, thrombocytopenia, diarrhea, temperature greater than 40.6 degrees C, and peripheral edema were rarely dose limiting. Thirty-two patients were evaluable for response. After 4 weeks of treatment, 21 patients had stable disease, three patients had a minor response, and one patient had a partial response. Significant lymphokine-activated killer cell (LAK) activity was seen in seven patients (22%) and required 5 x 10(6) units/m2 of IL-2. Those who had progressive disease had significantly less LAK activity than those with either stable disease or a response. This therapy also induced more than 60 units/ml of endogenous gamma-interferon 4 h after the i.v. IL-2 administration. This study demonstrates that (a) intermittent i.v. bolus IL-2 therapy can generate LAK activity, (b) LAK activity may be associated with an antitumor response, (c) significant levels of gamma-interferon are induced by this therapy, and (d) IL-2 and IFN-beta given three times weekly i.v. is both tolerable and biologically active. The recommended Phase II dose is 5 x 10(6) units/m2 of IL-2 plus 6 x 10(6) units/m2 of IFN-beta.
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PMID:A phase I study of recombinant interleukin 2 plus recombinant beta-interferon. 313 24

History of diagnosed illnesses, medical symptoms, and reproductive outcomes and their relation to combat intensity and herbicide exposure were studied, via a mailed questionnaire, among 6810 American Legionnaires who served during the Vietnam War (42% in Southeast Asia, 58% elsewhere). Heart disease, venereal disease, and benign fatty tumors were reported significantly more often by Vietnam veterans than by controls. Combat intensity was significantly dosage-related to history of high blood pressure, ulcers, arthritis and rheumatism, genito-urinary problems, nervous system disease, major injury, hepatitis, and benign fatty tumors. Agent Orange exposure was significantly dosage-related to history of benign fatty tumors, adult acne, skin rash with blisters, and increased sensitivity of eyes to light. Rates of the latter two conditions and of change in skin color were especially elevated in men whose military occupations involved direct handling of herbicides. Five "symptom complex" scales were constructed via factor analysis to measure degrees of feeling faint, fatigue or physical depression, body aches, colds, and skin irritation. Means of all five scales were significantly higher in Vietnam veterans compared to controls, and in herbicide handlers compared to nonhandlers. Both combat and Agent Orange exposure were significant, independent predictors of each of the five scales. Neither combat nor Agent Orange exposure was associated with difficulty in conception, time to conception of first child, or to birthweight or sex ratio of offspring, but maternal smoking was strongly related to reduced birthweight. The percentage of spouses' pregnancies which resulted in miscarriages was significantly higher for Vietnam veterans than controls (7.6% vs 5.5%, P less than 0.001). Logistic regression analysis showed that Agent Orange exposure and maternal smoking were both independently and significantly associated with miscarriage rates in a dose-related manner.
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PMID:Health and reproductive outcomes among American Legionnaires in relation to combat and herbicide exposure in Vietnam. 326 69


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