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)

A 49-year-old woman had a six-week history of increasing shortness of breath and fatigue. X-ray films and pulmonary scans showed multiple areas of emboli, especially in the right lung. Treatment with heparin was unsuccessful, and although a repeat scan showed only slight changes, the patient's condition deteriorated. Acute pulmonary edema and ventricular tachycardia preceded her death. Autopsy revealed a primary intimal sarcoma with osteogenic elements arising in the posterior leaflet of the pulmonary valve and obstructing the main pulmonary artery and its right branch.
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PMID:Primary intimal sarcoma of pulmonary valve and trunk with osteogenic sarcomatous elements. Report of a case considered to be pulmonary embolus. 106 72

A phase I trial of piritrexim was conducted by use of a prolonged, low-dose oral schedule. A number of different regimens were tested, including daily dosing for 21 days followed by 7 days of no drug therapy; continuous dosing; and daily dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest. Dose escalation was accomplished by increasing the dosing frequency from once a day to twice a day and then to three times a day and by increasing the number of days of administration. Fifty-one patients with advanced cancer were entered in the study. One hundred twenty-four (96%) of 129 courses were considered assessable. Myelosuppression proved to be the dose-limiting toxic effect. Other toxic effects included stomatitis, nausea and vomiting, anorexia, diarrhea, skin rash, fatigue, and elevation of liver transaminase levels. Antitumor activity was observed in patients with melanoma and bladder cancer, and disease stabilization occurred in those with sarcoma and pheochromocytoma. The recommended dosing schedule for phase II clinical trials is 25 mg three times a day for 5 days for 3 consecutive weeks followed by 1 week of no drug therapy.
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PMID:Phase I trial of piritrexim capsules using prolonged, low-dose oral administration for the treatment of advanced malignancies. 198 18

Merbarone, a nonsedating derivative of thiobarbituric acid, has demonstrated excellent activity against certain murine tumors, including L1210 and P388 leukemias, B16 melanoma, and M5076 sarcoma. Preclinical studies suggested that the antitumor effects of this drug were schedule dependent, since repeated dosing increased killing of tumor cells when compared to intermittent injections. We have completed a Phase I clinical and pharmacological study of merbarone in which the drug was administered both as a 2-h infusion and as a continuous i.v. infusion over 24 h. In view of the increased toxicity observed in animals following bolus injections and the possibility of schedule-dependent anticancer activity, a schedule of drug administration daily for 5 days was selected. Fifty patients with advanced cancer were treated at dose levels that ranged from 100 to 1500 mg/m2/day. When the drug was administered by peripheral vein, phlebitis was observed at the infusion site at daily doses greater than or equal to 150 mg/m2. Therefore, all patients who received drug doses greater than or equal to 200 mg/m2 were treated by continuous i.v. infusion using central venous catheters. Renal insufficiency, initially observed at a dose of 1000 mg/m2/day, was the dose-limiting toxic reaction at 1500 mg/m2/day. Three of five patients treated at the highest dose level were unable to complete the infusion due to this effect. Marked hypouricemia was observed in all patients. Other toxic effects were mild and included nausea, fatigue, leukopenia, thrombocytopenia, and anorexia. Alopecia was noted in several patients who received doses greater than or equal to 1000 mg/m2/day. No major antitumor effects were observed. Dose-dependent, steady-state plasma concentrations of merbarone were reached within 24-48 h after beginning the continuous i.v. infusion. Elimination of drug from plasma followed a two-compartment model, with a t1/2 alpha of 4.2 h and a t1/2 beta of 15.3 h. Renal excretion of merbarone and its major metabolites accounted for less than 30% of the administered dose. We conclude that merbarone is relatively well tolerated with few constitutional symptoms. The current formulation of the drug causes phlebitis when administered by peripheral vein, and renal insufficiency is commonly observed at daily doses which exceed 1250 mg/m2. The recommended dose for extended Phase II evaluation is 1000 mg/m2/day daily for 5 days administered by central venous catheter.
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PMID:Phase I clinical and pharmacological study of merbarone. 229 63

Twenty-five patients with disseminated cancer (nine with renal cell carcinoma, five with melanoma, three with Hodgkin's lymphoma and chronic myelocytic leukemia [CML], two with soft tissue sarcoma, one each with large-cell lymphoma, breast cancer, and colon cancer), 13 males and 12 females, aged 25 to 68, were treated with recombinant human interleukin-2 (rIL2) by continuous infusion and adoptive transfer of autologous lymphocytes activated in vitro with IL2. Patients underwent leukapheresis on days 1, 8, 15, and 22 of the treatment. Cells, bulk activated for 20 hours in serum-free culture medium with 1,000 U IL2/mL in transfusion transfer packs as culture vessels, were transfused the following day. The infusion of IL2 by continuous infusion for six days started immediately after each adoptive transfer for 4 weekly courses. The dose of IL2 was escalated weekly in each patient; starting doses of IL2 were also escalated in subsequent cohorts of patients until maximally tolerated doses were reached. Nine patients had objective tumor regressions (three with renal cell cancer, two with Hodgkin's lymphoma, and one each with melanoma, sarcoma, breast, and colon cancer). Six responses were partial, two were minor, and one was mixed. Responding patients were maintained with IL2 by continuous infusion for six days every 6 to 8 weeks, without adoptive cell transfer. The median duration of responses was 16 weeks (3 to 60 + weeks). Tumor regression was related to the dose of IL2 (greater than or equal to 3.4 x 10(6) U/m2/d for six days) and to the in vivo lymphoproliferative effects of the lymphokine, but not to the total number of cells adoptively transferred. Side effects of treatment were transient and quickly reversible. Renal, hepatic dysfunction, and dyspnea were directly related to the dose of IL2 and to lymphocytosis. Other toxicities were mild hypotension with mild fluid retention, oral mucositis, anemia, thrombocytopenia, fever, and fatigue.
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PMID:Recombinant interleukin-2 by continuous infusion and adoptive transfer of recombinant interleukin-2-activated cells in patients with advanced cancer. 266 33

The clinical and radiological features of three fatigue fractures developing along the medial aspect of the distal femoral diaphysis are described. All three patients were skeletally immature and were referred with the radiographic diagnosis of a probable sarcoma of bone. The plain radiographic findings consisted of an uninterrupted single lamella of periosteal new bone arising medially from the distal femoral diaphysis. Bone scans showed no evidence of hyperaemia on the vascular phase and revealed a fusiform focus of increased uptake in the postero-medial cortex of the lower femoral diaphysis on the 3-h images. Computed tomography showed increased attenuation of the medulla due to fibrosis and an absence of a soft-tissue mass. Periosteal callus was present and a cortical fracture through the medial femoral cortex was identified in two cases. The features that distinguish a fatigue fracture of the femur from a sarcoma are discussed.
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PMID:Fatigue fractures of the femoral diaphysis in the skeletally immature simulating malignancy. 281 57

The clinical and radiological features of nine fatigue fractures developing along the soleal line of the posteromedial cortex of the proximal tibia are described. Seven patients were referred with the diagnosis of a probable malignant sarcoma of bone. All nine patients were male and all but one were 18 years of age or less. Only two gave a history of a recent increase in physical activity. The plain radiographic findings consisted of an uninterrupted, lamellar, periosteal reaction arising medially and posteriorly in the proximal tibia with the fracture seen through the thickened posterior cortex. Bone scan revealed a fusiform focus of increased uptake in the posteromedial cortex of the tibia with varying degrees of activity in the adjacent metaphysis. Computed tomography, on a soft-tissue window, showed perifracture oedema and the absence of a soft-tissue mass. The attenuation of the underlying medulla was increased as a result of fibrosis and hyperaemia. On an extended window setting, both periosteal and endosteal callus was identified, maximal in the posteromedial tibia, and the fractures, multiple in two cases, were best demonstrated on a cortical window. Clinical and radiological features that differentiate a fatigue fracture of the tibia from a sarcoma are discussed.
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PMID:Fatigue fractures of the proximal tibia simulating malignancy. 319 15

This study represents the examination of 14 primary, malignant pleural tumours--10 mesotheliomas and 4 sarcomas--in respect of the radiological appearance and clinical signs and symptoms. The presentation was widely different in the mesothelioma patients: 3 presented the radiological image of a mantle-like apicocaudal callosity. In 3 patients and extrapulmonary space-occupying growth was seen; one case presented with an interlobar effusion. Pleural effusion was additionally present in 6 cases. Of the 4 sarcoma patients, 3 presented with an intrapulmonary space-occupying growth and one only with an extrapulmonary lesion. Pleural effusion was definitely seen in 2 patients with pleural sarcoma. Therapy-resistant refractory thoracic pain was the principal clinical sign. Other symptoms were not so frequent, such as loss of body weight, tiredness, dyspnoea, hemoptysis and cough.
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PMID:[Primary malignant tumors of the pleura]. 372 17

Twenty patients with soft tissue sarcoma were treated with iv human fibroblast interferon (beta-interferon). Each cycle of treatment involved 5 X 10(6) units over 10 minutes, then 5 X 10(6) units iv over 3 hours daily X 10 with cycles repeated every 20 days X 3. Maintenance therapy was given twice weekly if disease was stable or responsive after three therapy periods. One patient had a partial response to treatment and six patients experienced stable disease for variable periods of time. Toxicity (fever, fatigue, leukopenia, hepatic enzyme elevations) was moderate and tolerable; therapy (except in one case of profound granulocytopenia) was neither interrupted nor discontinued because of toxicity. We conclude that beta-interferon in the dose and schedule used has limited value for soft tissue sarcoma.
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PMID:Treatment of soft tissue sarcoma with fibroblast interferon (beta-interferon): an American Cancer Society/Illinois Cancer Council Study. 394 93

Transcription and translation activity in relation to oxygen consumption have been measured in isolated liver cells from freely fed tumor-bearing mice and compared with that of freely fed controls. The liver cells were isolated by perfusion of livers in situ with a collagenase containing buffer. Adult nongrowing mice with a methylcholanthrene induced sarcoma were used. Liver cells under the remote effect of the malignant tumor had increased transcription and translation of hepatic proteins in spite of decreased cellular oxygen consumption. The mechanisms behind increased hepatic protein synthesis concomitant with decreased energy production in the tumor-influenced liver are unknown, but we suggest that the hepatic translation of some genetic information may be of importance for the host survival in the tumor-bearing condition.
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PMID:Transcriptional and translational activity in relation to oxygen consumption in isolated liver cells from sarcoma-bearing mice. 619 66

To determine the maximum tolerated dose (MTD) of escalating doses of interferon-alpha-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisplatin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), colorectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder (1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c. on days 1-5 and then three times weekly with DDP (75 mg/m2, day 1) and 5-FU [750 mg/m2, days 1-5, continuous infusion (CI) on a 28-day cycle. The first two patients treated at level I (3 x 10(6) U/m2 s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accident (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 toxicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those with prior exposure to DDP. This resulted in grade 3 toxicity in terms of nausea, vomiting, fatigue and leukopenia but in no further CNS event. All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The recommended dose of IFN is 2 x 10(6) U/m2 s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m2, days 1-5, CI) and DDP (75 mg/m2, day 1) on a 28-day cycle.
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PMID:A phase I study of recombinant human interferon alpha-2b combined with 5-fluorouracil and cisplatin in patients with advanced cancer. 788 58


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