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)

Patients who have undergone thyroidectomy for thyroid carcinoma are frequently subjected to periods of induced severe hypothyroidism in preparation for 131I whole body scanning and measurement of serum TG. These two tests are crucial in evaluating the patient's clinical status and determining administration of 131I or other necessary treatment. Severe hypothyroidism produces fatigue, weight gain, depression, inability to carry out usual activities, and occasionally significant illness. We compared the efficacy of inducing moderate hypothyroidism by cutting replacement therapy in half, to a standard method. In the standard preparation, patients substituted triiodothyronine for thyroxine replacement over a 3-week period, and then omitted hormone therapy for 3 weeks. For the subsequent scan, 6 to 12 months later, the thyroxine dosage was cut in half. TSH levels were assessed 4 weeks later, and if adequately elevated, whole body scanning was conducted at the end of the fifth week. Pulse, weight, clinical symptoms, thyroid hormone levels, and some clinical chemistries were evaluated prior to each scan, and some of the tests were also carried out during the interval between scans. Moderate hypothyroidism induced by the half-dose protocol induced TSH elevations above the target level (25-30 microU/mL) at 5 weeks in most patients. Typically TSH of 15 microU/mL in the previous week predicted adequate elevation of TSH at the time of scan. Half dose therapy can be prolonged, if necessary, especially in patients who begin with extreme suppression of TSH, or if a higher TSH is desired. Pulse, weight gain, and cholesterol were significantly different in the two protocols, and the patient's subjective evaluation of hypothyroid symptoms was significantly reduced. Reduction of thyroxine replacement dosage to half the usual amount, in patients with thyroid cancer, allows after 5 weeks in most patients sufficient elevation of TSH for whole body scanning and measurement of TG levels. This simple and economical procedure drastically reduces symptomatology of hypothyroidism and makes this key procedure much more tolerable to patients.
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PMID:Moderate hypothyroidism in preparation for whole body 131I scintiscans and thyroglobulin testing. 1566 27

The aspartate transcarbamoylase inhibitor, N-(phosphonacetyl)-L-aspartate (PALA), synergistically enhanced the cytotoxicity of a combination of 5-fluorouracil (5-FU) and interferon-alpha (IFN) against human colon cancer cell lines in vitro. To test the efficacy of this combination in the clinical setting, patients with locally advanced or advanced gastric carcinoma were treated with the combination of PALA, 5-FU and IFN (PFI). Patients were required to have biopsy-proven disease beyond the scope of surgical resection, measurable disease, no prior chemotherapy, adequate bone marrow, renal and hepatic function, to be fully ambulatory and to have given informed consent. Drug was administered as follows: PALA, 250 mg/m2, 15 min i.v. infusion, days 1, 15, 22, 29, and then weekly; 5-FU, 750 mg/m2 daily x 5 as a continuous i.v. infusion beginning day 2, then at 750 mg/m2 days 16, 23 and 30, then weekly; IFN, 9 MU subcutaneously three times per week beginning day 2. There were 22 patients enrolled. The major toxicities were fatigue and associated neurotoxicity, with acceptable gastrointestinal and haematological toxicities. There was one complete responder (5%) and 3 partial responders (14%); two of these responses were durable (> 3 years). Despite this modest clinical activity, other regimens for advanced gastric cancer such as FAMTX and ELF appear to have greater activity with comparable toxicity.
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PMID:Phase II trial of N-(phosphonacetyl)-L-aspartate (PALA), 5-fluorouracil and recombinant interferon-alpha-2b in patients with advanced gastric carcinoma. 875 62

The activity and toxicity of UFT (Tegafur and Uracil) in a 4:1 molar concentration, plus leucovorin (LV), were evaluated in the treatment of 45 patients with advanced, bidimensionally measurable metastatic colorectal carcinoma. Initially 350 and later 300 mg/m2/day, plus 150 mg LV, as administered in divided doses every 8 h for 28 days. After two courses of treatment, responses were evaluated. The overall response rate was 42.2%, with responses observed in liver (n = 18), lung (n = 6), and bone (n = 1). Five of the 7 patients who received 350 mg/m2 UFT experienced prolonged grade 3 diarrhea, resulting in a dose reduction to 300 mg/m2; 9 patients in the 300-mg/m2 group experienced grade 3 diarrhea, vomiting, abdominal cramping, and fatigue. Minor toxic effects included oral mucositis and rash. The oral regimen of 300 mg/m2/day UFT, plus 150 mg/day LV, administered for 28 days appears to have significant activity against metastatic colorectal carcinoma. The treatment is well tolerated; neutropenia did not occur, and oral mucositis was not significant, even though both are characteristic of intravenous schedules of 5-fluorouracil plus LV. The results of this trial constitutes the basis of phase III clinical trials comparing this oral schedule with intravenous 5-FU and LV to compare clinical efficacy, impact on well-being, and cost. In addition, the current National Surgical Adjuvant Breast and Bowel Project (NSABP) adjuvant colon clinical trial (CO-6) will compare this 28-day schedule of UFT plus oral leucovorin with a weekly regimen of intravenous 5-fluorouracil plus leucovorin in the postoperative adjuvant therapy of Dukes' B and C colon cancer patients.
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PMID:Phase II study of UFT plus leucovorin in colorectal cancer. 897 80

A combination of platinum and a taxane is regarded by many as the optimum treatment for advanced epithelial ovarian carcinoma. A recent meta-analysis has suggested that the addition of an anthracycline to platinum-based chemotherapy is associated with a significant survival advantage. We are therefore conducting an ongoing phase I/II study combining drugs from these three classes. We report here the first phase using carboplatin at an area under the concentration-time curve of 7, doxorubicin 50 mg/m2, and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 over 3 hours. The treatment was given on a 3-weekly cycle and granulocyte colony-stimulating factor was given if the nadir neutrophil count fell below 0.5 x 10(9)/L and was continued until recovery. Toxicity was assessed according to the Common Toxicity Criteria. All patients were required to have advanced ovarian cancer (stage IC to IV) but be ineligible for standard chemotherapy trials or to have advanced gynecologic malignancy, such as mixed mullerian tumor, fallopian tube carcinoma, coelomic carcinoma, or primary peritoneal carcinoma. To date, seven patients have been treated, and all were of performance status 0 to 2, 18 to 70 years old, with a life expectancy of > or = 3 months. Hematologic toxicity was significant, with all patients having grade 3/4 thrombocytopenia and six of seven grade 3/4 leukopenia. There was, however, only one grade 3/4 infection. Three patients have experienced fatigue, which in two cases was severe, and one patient had grade 3/4 stomatitis. Dose reduction was due to myelosuppression and was required in five patients. Five patients were evaluable for response, all of whom have obtained complete or partial response. There has been no clinical evidence of cardiotoxicity, but four patients had grade 1/2 cardiotoxicity as measured by left ventricular ejection fraction. We conclude that this combination is active and has acceptable but significant toxicity. It is only suitable for very fit patients, and we are currently assessing ways of reducing toxicity.
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PMID:Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. 904 34

Clinical evaluation in oncology has typically focused on outcome indicators, while less attention has been paid to how treatment affects quality of life (QOL) of the patient. In this article some general aspects of quality of life are discussed, a short review of published data on QOL in patients with prostate cancer is given and results of a QOL study executed by the authors on patients with lymph node positive prostatic cancer are presented. The purpose of the study was to examine the impact of immediate or delayed treatment (after objective progression) in patients with prostatic carcinoma (T1-3 N1-3 M0) on quality of life parameters. To this end an extended questionnaire was constructed. Fifty-five patients participated. Assessment was performed twice, in 1994 and 1995. The comparison between patients with and patients without treatment showed in 1994 as well as in 1995 significant differences for hormonal treatment side effects such as sexual functioning and hot flushes, all of which were experienced more frequently by treated patients. In 1994 the treated patients experienced more psychological distress while in 1995 they showed worse physical function, less energy and more fatigue when compared to patients under surveillance. The premise that active treatment would improve the psychological quality of life was not sustained. In addition global health status and quality of life were identified as independent factors for progression in untreated patients with lymph node positive prostate cancer. Finally, an increase in prostate-specific antigen (PSA) in hormonally treated patients not only indicated hormonal escape but also a decrease in QOL.
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PMID:Quality of life in patients with prostatic carcinoma: a review and results of a study in N+ disease. Prostate-specific antigen as predictor of quality of life. 914 92

We previously reported results of a Phase II trial of UFT [Taiho Pharmaceutical Ltd., Tokyo, Japan; (BMS-200604) Bristol-Myers Squibb, Princeton, NJ], an oral 4:1 molar concentration of uracil and tegafur, plus oral leucovorin for metastatic colorectal carcinoma (Pazdur et al., J. Clin. Oncol. 12:2296-2300, 1994]. Our results demonstrated that a 28-day schedule of this combination produced a response rate similar to that obtained with conventional intravenous fluorouracil (5-FU)-plus-leucovorin regimens but without the severe or life-threatening neutropenia or oral mucositis that complicates intravenous 5-FU regimens. The current Phase I trial examines the dose-limiting toxic effects and maximum tolerated dose of a 14-consecutive-day schedule of UFT plus oral leucovorin in 14 patients who had histologically proven cancer and had received prior chemotherapy. The daily UFT plus leucovorin dose was divided into three doses administered orally every 8 hours. In this study, the UFT dose was escalated while the leucovorin dose remained at 150 mg/day. Of the 14 patients, 4 were initially treated at the 350-mg/m2/day UFT level for 14 days without any dose-limiting toxic reactions. Subsequently, another 7 patients were treated at the 400-mg/m2/day level; grade 3 diarrhea developed in 3 of these 7 (with severe abdominal cramping in 2 cases and severe nausea and vomiting unresponsive to antiemetics in the third). To better define the starting dose for phase II studies, an additional 3 patients were treated at the 350-mg/m2/day dose level. Of the total 7 patients treated at 350 mg/m2/day, grade 3 toxic events (diarrhea) developed in 2 patients. Grade 1-2 toxic effects noted at this level included fatigue, stomatitis, skin rash, abdominal pain, nausea, and vomiting. Neither partial nor complete responses were observed in this trial. The maximum tolerated dose of this schedule is 350 mg/m2/day UFT plus 150 mg/day oral leucovorin. However, because of this schedule's inferior dose intensity compared with that of the 28-day schedule of UFT plus leucovorin, subsequent development of UFT in the United States has focused on the 28-day regimen.
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PMID:Phase I trial of uracil-tegafur (UFT) plus oral leucovorin: 14-day schedule. 922 Feb 91

A 59-year-old woman was admitted to the hospital with a one-month history of hemoptysis, generalized fatigue, and a high fever. A chest X-ray film obtained on admission showed a massive right-sided pleural effusion. Examination of an aspirate showed a high level of amylase, and bacteria that were the same as oral bacteria. Closed drainage yielded ichorous pus and food residues, which led us to the diagnosis of empyema caused by esophageal perforation. Esophagography and fiberoptic esophagoscopy revealed that an esophagobronchial fistula related to an advanced esophageal carcinoma had caused the empyema. Surgical resection was done, and the patient was alive at the time of this writing, 7 months after she was first treated. Esophageal carcinoma is sometimes accompanied by esophagobronchial fistula. Patients with this condition usually have severe respiratory symptoms; those presenting with empyema are rare. Esophageal carcinoma must be carefully ruled out as the cause of empyema.
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PMID:[Esophagobronchial fistula and empyema resulting from esophageal carcinoma]. 923 40

We report a rare case of brain tumor metastasizing from an adrenocortical carcinoma. A 47-year-old man was referred to our department on September 21, 1995, with complaints of episodic loss of consciousness and severe left motor weakness. There was a past history of left adrenalectomy performed in the Department of Surgery of our hospital 9 months before. On admission, computed tomography (CT) and magnetic resonance imaging (MRI) revealed two well circumscribed masses in the right frontal lobe with peritumoral, marked brain edema and metastasis to the lung. The brain tumor was successfully removed via frontal craniotomy 4 days after admission. Histological examination of the tumor specimen revealed metastatic anaplastic cell carcinoma, indicating metastasis from an adrenocortical carcinoma. After chemotherapy with cisplatin, pepleomycin and pirarubicin, he was discharged without neurological deficit. Two months postoperatively, however, the patient received 50 Gy of telecobalt radiation therapy to the whole brain because of recurrence. Three months after-wards, the patient returned complaining of general fatigue. Chest CT scan revealed further enlargement of the lung lesions. Despite repeated chemotherapy, the patient died of lung metastases eight weeks later. Central nervous system metastasis from adrenocortical carcinoma is exceedingly rare. To the best of our knowledge, only 5 cases have been reported. We report here another case of brain metastasis from adrenocortical carcinoma possibly via lung metastasis, and review the pertinent medical literature.
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PMID:[Central nervous system metastasis from non-functioning adrenocortical carcinoma: report of a case]. 938 70

Menetrier's disease (MD) or polyadenomes en nappe is a form of hypertrophic gastropathy occurring primarily in middle-aged males. Patients generally present clinically with dyspepsia and, on occasion, with hypoproteinemic edema and anemia. The latter feature, when combined with the radiographic appearance of the stomach in MD, can lend to confusion with carcinoma and malignant lymphoma. To illustrate this diagnostic problem, a case is reported of a 41-year-old female who initially presented to her family physician with symptoms of easy fatigue and dyspnea on exertion and signs of pallor and ankle edema. Pertinent laboratory findings included a hemoglobin of 2.8 g/dL, hematocrit of 10.3 percent, mean corpuscular volume of 63.4 mu 3, a serum albumin of 2.7 g/dL, and heme positive stools. Endoscopic examination revealed a circumferential polypoid mass involving the cardia and fundus of the stomach with relative sparing of the antrum. A CT scan of the abdomen and pelvis showed a large mass in the stomach which the radiologists and gastroenterologists believed probably represented a lymphoma or gastric carcinoma. A total gastrectomy specimen exhibited features of MD. Routine bright-field microscopy and immunohistochemical reactivity for transforming growth factor-alpha confirmed the diagnosis of MD. Moreover, ulceration of the tips of some of the hypertrophied gastric folds provided an explantation for the iron deficiency anemia. Awareness that MD may present with anemia will help in the differential diagnosis with lymphoma and carcinoma.
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PMID:Menetrier's disease presenting with iron deficiency anemia. 951 79

Patients with colorectal carcinoma progressing after a 5-fluorouracil (5-FU)-containing regimen were eligible. One treatment cycle consisted of repeated administrations of 5-FU combined to folinic acid for six times and to oxaliplatin for three times over 50 days. 5-FU was given at the dose of 2.6 g/m2 as a continuous infusion over 24 h on days 1, 8, 22, 29 and 43 preceded by i.v. folinic acid (FA) at a dose of 500 mg/m2 over 1 h. Oxaliplatin was given 1 h after 5-FU at the dose of 130 mg/m2 over a 2 h infusion on days 1, 22 and 43. A total of 37 patients were treated according to this schedule. The rates of objective responses after the first and second treatment cycles were 28 and 17%, respectively, with rates of tumor growth control, i.e. including the stabilizations, of 55 and 28%. The median duration of response was 10 months and the median duration of stabilizations was 6 months. The median survival time from initiation of oxaliplatin-containing therapy is 10 months (2-28+). The median survival time from the diagnosis of metastatic disease is 24 months (2-40+). The main toxicities were leucopenia, diarrhea, fatigue and paresthesias. The combination of 5-FU/FA/oxaliplatin was well tolerated and appears as a meaningful therapy after failure of a previous 5-FU-containing treatment.
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PMID:Oxaliplatin combined to 5-fluorouracil and folinic acid: an effective therapy in patients with advanced colorectal cancer. 963 19


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