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)

This report is an analysis of the medical records of 83 patients registered between 1960 and 1980 at Helsinki University Central Hospital as having malignant pleural mesothelioma. 65 of 83 patients had histologically confirmed malignant mesothelioma, and are the focus of this analysis. The remaining 18 (22%) patients were excluded because malignant mesothelioma was only confirmed cytologically, or because the primary tumor was not a mesothelioma. The ratio of men to women was 2:1.30 of 65 (46%) patients were not known or not likely to have been exposed to asbestos. The main symptoms at presentation were dyspnea, cough, chest pain, fatigue and weight loss. The median survival from diagnosis was 12 months, and from the onset of symptoms 18 months. Clinical stage and performance status were significant prognostic factors. Hematogenous metastases were present at autopsy in most cases. Disease and performance status therefore need to be well established and documented in clinical trials involving mesothelioma.
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PMID:Diagnosis and prognostic factors in malignant pleural mesothelioma: a retrospective analysis of sixty-five patients. 143 23

In light of in vitro and preclinical animal model data suggesting potential additive or synergistic antitumor effects from the combined use of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), we conducted a phase I study employing escalating doses of each agent in 36 patients with solid tumors to determine the maximum tolerated dose (MTD). Patients were given an intramuscular (i.m.) injection of IFN-gamma, followed 5 min later by an i.m. injection of TNF-alpha, each agent in different sites, every other day for ten doses over 20 days. Patients received 10, 50, or 100 micrograms/m2 of each agent throughout the treatment course. No dose modifications were made. Patients suffering serious toxicity had therapy stopped and were considered to be off-study. All patients experienced fatigue, and 36% spent over half their time in bed on treatment days. Fever and chills were nearly universal. Mild to moderate elevations in serum transaminase levels were noted in 44% of patients, and 44% developed transient microscopic hematuria. Although 81% of patients had anorexia, only 17% of patients lost more than 3 kg of body wt during the 3 weeks of therapy. Because two of three patients receiving 100 micrograms/m2 of both agents developed serious toxicity (one fever greater than 105 degrees F, one thrombocytopenia 43,000/mm3), the MTD was established to be 100 micrograms/m2 of IFN-gamma plus 50 micrograms/m2 of TNF-alpha. The use of aspirin did not significantly alter the toxic effects of the agents. One patient with melanoma had a mixed response and one patient with mesothelioma transiently cleared his ascites of malignant cells.
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PMID:Phase I evaluation of recombinant tumor necrosis factor given in combination with recombinant interferon-gamma. 179 Jan 43

As previously reported, cytotoxic synergy is produced when clinically achievable concentrations of cytarabine (Ara-C) and hydroxyurea (HU) are used as potential inhibitors of in vitro DNA repair in cisplatin (cis-Pt)-treated human colon carcinoma cells. This pilot study was subsequently designed to duplicate the in vitro dose and schedule and to determine the toxicity of this three-drug combination in two cohorts of patients. 21 patients had received prior chemotherapy and 19 were not previously treated. All patients had refractory solid tumors. They received monthly cycles of an oral loading dose of 800 mg/m2 HU followed every 2 h by 6 oral doses of 400 mg/m2, a 12-h continuous infusion of 200 or 250 mg/m2/h Ara-C concurrent with the HU, and then 100 mg/m2 cis-Pt over 1 h. A total of 95 cycles were given with the expected toxicities of nausea and vomiting and fatigue but not major acute toxicity observed. Thrombocytopenia was significant but transient and was dose-limiting only for patients who had received prior therapy. The median platelet nadir after one cycle was 43,000/microliters for all patients and 67,000/microliters for those who had not undergone prior treatment. Azotemia was treatment-limiting in responding and stable patients, suggesting the possibility of synergistic nephrotoxicity. Interestingly, there were early transient rises in both uric acid and lactate dehydrogenase (LDH). Partial responses were seen in 9 of 32 patients with measurable disease and there was significantly improvement in 5 of 8 patients with only evaluable disease. The responses or improvement occurred in patients with non-small-cell lung cancer, breast carcinoma, glioblastoma, ovarian carcinoma, small-cell lung cancer, and mesothelioma. Of these 14 patients, 9 had failed prior chemotherapy regimens. Significantly, responses were observed in 3 of 8 patients who had previously received cis-Pt, suggesting that the HU/Ara-C combination modulated cis-Pt resistance. Because of these encouraging results, a second pilot study has been initiated with modifications dictated by the toxicity issues raised in this trial.
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PMID:Cisplatin preceded by concurrent cytarabine and hydroxyurea: a pilot study based on an in vitro model. 224 91

The Patient was a 72-year-old man who presented with dyspnea and general fatigue. Chest X-ray and CT-scan at the admission showed bilateral pleural effusion with collapse of the left lung and pericardial effusion. Cytology from the left pleural effusion suggested malignant mesothelioma. For this reason, malignant mesothelioma of the left pleura was diagnosed clinically and it was supposed to have spread subsequently to the pericardium. At autopsy, entire surface of the heart was found to be encroached in a diffuse fashion by a thick layer of mesothelioma tissues, which formed a small mass around the left pulmonary vein over the left atrium and invaded deep into the myocardium of all cardiac chambers. The endocardium and the intima of the left pulmonary vein were free of the invasion. The parietal pericardium adhered in places to the cardiac lesion, but no direct invasion to the adjacent pleurae through the pericardial wall was present. The left pleura over the lung and chest cavity disclosed only a superficial invasion by similar mesothelioma which was identifiable only on microscopic study. No distant metastasis was present in any thoracic and other organs as well as lymph nodes including the hilar ones of the lung. It seemed most likely from this anatomical finding that the primary site of the present mesothelioma was in the pericardium (visceral) and the tumor spread to the left pleura by a continuous extension along the outside of the left pulmonary vein. Primary malignant mesothelioma of the pericardium is of very rare occurrence and we found only 51 cases of it in the Japanese literature since 1915.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Primary malignant mesothelioma of the pericardium masquerading as malignant pleural mesothelioma: report of an autopsy case and review of the reported cases in Japan as to its invasion to neighboring organs]. 268 98

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

A Phase I study was carried out with ricin, a plant toxin acting by inhibiting protein synthesis, on 54 cancer patients with advanced disease. Ricin was given as i.v. bolus injections every two weeks at dose levels ranging from 4.5 to 23 micrograms/sq m of estimated body surface area. Ricin was well tolerated at doses up to 18 to 20 micrograms/sq m. At these levels and at higher levels, flu-like symptoms with fatigue and muscular pain appeared and, in some patients, nausea and vomiting occurred also. No myelo-suppression was seen. Antibodies to ricin were detected in serum after two to three ricin injections. Ricin was eliminated from blood according to first order kinetics. At each dose level, the plasma concentrations, as well as the side effects, showed only minor differences between patients. The highest dose given, 23 micrograms/sq m, gave plasma concentrations twice those found previously to be therapeutically effective in tumor-bearing mice. Of 38 evaluable patients, one patient with lymphoma had a partial response. Stable disease was observed in four patients with renal cancers, in two with soft tissue sarcomas, and in one patient each with mesothelioma, thyroid, and rectal cancer. A dose of 23 micrograms/sq m is recommended for Phase II trials of ricin.
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PMID:Phase I study of the plant protein ricin. 669 85

An observation of malignant peritoneal mesothelioma in a man of 61 is presented. The clinical signs included fatigue, loss of weight, enlarged abdomen. The duration of the disease was 8 months. The autopsy revealed a whitish tumor of the peritoneum of cartilage density with numerous nodules 0.5-1.5 cm in diameter. The tumor overgrew the liver, spleen, pancreatic gland, stomach, and intestinal loops forming a single conglomerate. In the peritoneal cavity there were 4000 ml of transparent yellowish fluid. The visceral and parietal pleura on the left was thicker and covered with small whitish nodules. Histological examinations showed the peritoneum to be thickened, sclerosed and hyalinized. In the thickness of the fibrous stroma there were numerous slits lined with mesothelial cells. There were metastases in regional lymph nodes. The tumor had the structure of a malignant mesothelioma of the epithelial-like variant.
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PMID:[Malignant mesothelioma of the peritoneum]. 711 33

A 27-year-old woman presented with fatigue and dyspnea and was found to have a 2 x 4-cm mass in the pericardium, which was resected. Histologic examination demonstrated a well-differentiated papillary mesothelioma of the pericardium. Postoperatively, she received radiation therapy and had no evidence of recurrence 28 years later. It is extremely rare for this indolent variant of mesothelioma to arise in the pericardium.
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PMID:Curative resection of a well-differentiated papillary mesothelioma of the pericardium. 788 81

Except for benign pleural effusion, asbestos-related pulmonary complications, including asbestosis, malignant mesothelioma and bronchogenic carcinoma, usually occur more than 20 years after exposure. Pleural plaques and pleural thickening serve as markers for asbestos exposure, but they are not associated with an increased risk of malignancy. Clinical criteria for the diagnosis of asbestosis include a reliable history of asbestos exposure, an appropriate interval between exposure and disease detection, radiographic evidence of pulmonary fibrosis, decreased vital capacity and diffusing capacity, and bilateral posterior inspiratory crackles. A lung biopsy is indicated only to rule out other causes of interstitial lung disease. A history of dyspnea, pleuritic chest pain, fatigue, weight loss and pleural effusion in a former asbestos worker is suggestive of mesothelioma. Cigarette smoking greatly increases the risk of lung cancer in asbestos workers.
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PMID:Pulmonary complications of asbestos exposure. 804 65

Fourteen patients with diffuse malignant pleural mesothelioma (DMPM) were enrolled in a Phase II study to assess activity and toxicity of the systemic administration of recombinant (r)-alpha-interferon (IFN)-2b. The IFN schedule was: 3 x 10(6) IU i.m. days 1-4, 6 x 10(6) IU days 5-8, 10 x 10(6) IU days 9-12; then IFN was administered at 10 x 10(6) IU 3 days/week. If grades II-III toxicity occurred, IFN dose was reduced and drug continued at the previous dose level. All patients were evaluated by CT scan. Only one patient was not evaluable for response and toxicity because of inadequate follow-up. Of 13 evaluable patients, we observed 1 objective response, 6 stable disease, and 6 failures (3 progressive disease and 3 early interruptions due to subjective toxicity). The median time to progression was 19 weeks, and the median overall survival was 62 weeks. Toxicity was mild: of 13 patients evaluable for toxicity we observed fever (9 patients), flu-like syndrome (3 patients), fatigue (4 patients), anorexia (2 patients), myelosuppression (3 patients), and muscle pain (1 patient). The results of this study indicate only marginal activity of r-alpha-IFN in the treatment of DMPM.
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PMID:Recombinant interferon alpha-2b in the treatment of diffuse malignant pleural mesothelioma. 831 Oct 14


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