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)

Kaposi's sarcoma (KS) is a malignant neoplasm that develops in 20% to 30% of all acquired immunodeficiency syndrome (AIDS) cases. Kaposi's sarcoma primarily involves the skin, but can progress to involve the lungs, gastrointestinal tract, and liver. alpha-Interferon alone or in combination with zivoduvine has activity in acquired immunodeficiency syndrome-related KS, especially in patients with limited disease and CD4 lymphocyte counts over 400/mm3. Patients with progressive or symptomatic visceral disease, however, can be treated more effectively with cytotoxic chemotherapy. We have used a combination of doxorubicin, bleomycin, and vincristine (ABV) and have achieved response rates of over 80%. Discontinuation of therapy, however, is associated with relapse shortly after response (2 to 3 months). Thus, we have begun studies to define a safe and effective maintenance therapy. Such therapies should include antiretroviral agents since most patients succumb to other human immunodeficiency virus complications, and since human immunodeficiency virus directly, through viral proteins, and indirectly, through the induction of cellular genes, induces KS growth. Additionally, agents with antitumor activity and possible antiviral activity, such as alpha-interferon, may be potentially effective in maintenance therapies. We recently studied 21 patients in a phase I study of recombinant interferon alpha-2b (INTRON-A, Schering-Plough Corp, Kenilworth, NJ) alone following ABV chemotherapy. A dose of 10 million units, given in daily subcutaneous injections, was the maximal tolerated dose; higher doses were associated with intolerable fatigue, diarrhea, and fevers. We are currently conducting a phase I/II trial studying the combination of zivoduvine (500 mg/d) and recombinant interferon alpha-2b (5, 10, and 15 million units) as maintenance in patients with advanced or progressive KS.
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PMID:Phase I/II trials of alpha-interferon alone or in combination with zidovudine as maintenance therapy following induction chemotherapy in the treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma. 171 42

Psychosexual sequelae associated with surviving acute leukemia treated with conventional chemotherapy or with chemotherapy followed by bone marrow transplantation (BMT) were investigated in 70 patients who were off treatment for at least 1 year. Assessment of psychosexual function included frequency of sexual activity, satisfaction, body image, gender role identity, and adjustment in sexual relations. No differences between BMT and conventional chemotherapy survivors were found on any of these measures, despite the high probability of gonadal impairment with BMT. Compared with physically healthy norms, women survivors generally reported decreased sexual frequency and satisfaction, whereas both men and women survivors reported poorer body image. Longer time since completing cancer treatment predicted greater frequency of sexual activity in women but poorer body image for both men and women. Those survivors who reported decreased sexual frequency, satisfaction, and poorer body image reported greater psychological distress and decreased energy. Results indicate that psychosexual sequelae in survivors of leukemia occur frequently and warrant intensive investigation, particularly to address the need for an intervention in those most distressed.
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PMID:Long-term psychosexual adjustment of acute leukemia survivors: impact of marrow transplantation versus conventional chemotherapy. 173 Apr 1

We inserted Gianturco-Z stents in 17 patients with tracheobronchial stenoses on 18 occasions. Three patients had benign, all others malignant stenoses due to compression of the tracheobronchial tree by metastasising malignancies. In all cases the stents could be easily positioned and the patients experienced relief of their severe dyspnea. In one case there was fatigue breakage of the stent. The patient was therefore given a silicone tracheal stent.
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PMID:[Clinical experiences with the Gianturco-Z stent in endotracheal and -bronchial stenoses]. 173 73

The National Cancer Institute (NCI) Canada Clinical Trials Group conducted a phase II study of recombinant tumor necrosis factor (rTNF) given intravenously daily for 5 days every other week, in measurable metastatic renal cell carcinoma. Two of 26 patients responded with responses lasting greater than 200 days. Toxicity was severe including rigors, fever, headache, fatigue, hypotension, and localized pain. We conclude that rTNF, given as described, has only modest antitumor activity in renal cell carcinoma and produces considerable toxicity. We plan no further studies of rTNF in this disease.
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PMID:A phase II study of recombinant tumor necrosis factor in renal cell carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group. 173 50

A Phase II clinical trial of the combination of 5-fluorouracil (5-FU) and recombinant alpha-2a-interferon (alpha-2a-IFN) was conducted in 44 patients. Patients had not received chemotherapy previously and had measurable metastatic gastric carcinoma. 5-FU was administered as a continuous infusion at a dose of 750 mg/m2/d for 5 consecutive days and as an intravenous bolus at a dose of 750 mg/m2 weekly for 7 weeks beginning on day 12. Recombinant alpha-2a-IFN was administered subcutaneously at a dose of 9 x 10(6) U three times a week during weeks 1 to 8. Patients were examined for response during week 9. Of 44 patients entered, 40 could be examined for response. Nine patients experienced a partial clinical response and one achieved a complete response, for an overall response rate of 25% (95% confidence interval, 13% to 41%). The median duration of response was 13 weeks (range, 9 to 67 weeks) and the median survival time was 29 weeks. Grade 3 to 4 toxicities included granulocytopenia (nine patients), diarrhea (three patients), oral mucositis (seven patients), skin rash (one patient), and fatigue (four patients). One patient died of neutropenic sepsis. This regimen had modest activity with significant toxicity and produced responses of short duration. It did not appear to be superior to existing treatments of metastatic gastric carcinoma.
Cancer 1992 Feb 15
PMID:A phase II trial of 5-fluorouracil and recombinant alpha-2a-interferon in previously untreated metastatic gastric carcinoma. 173 78

We have investigated the pharmacokinetics, tolerance, and biological activity of recombinant human interferon-gamma (rHuIFN gamma) administered subcutaneously to cancer patients. Twenty-one patients with lymphoma and metastatic cancer received rHuIFN gamma (in doses of 0.1, 0.25, or 0.5 mg/m2) in two or three injections per week for up to 180 days. The most common adverse effects encountered were flu-like symptoms, fever and fatigue. The increase in body temperature after each administration ranged from 0 to 4 degrees C depending on the individual patient, but was unrelated to the rHuIFN gamma dose or its plasma concentration. The pharmacokinetic response of the patients after the two treatments showed a low intra-individual variability with respect to the plasma concentration/time profiles. However, as observed for the fever side-effect, the interindividual variation (CV greater than 50%) was high for the parameters area under the data points (AUC0-t) and maximum plasma concentration (cmax). Despite this high interindividual variability, the mean values obtained for AUC0-t and cmax after s.c. injection of rHuIFN gamma were approximately proportional to the dose administered: the injection of 0.1, 0.25 or 0.5 mg/m2 rHuIFN gamma resulted in AUC0-t values of 15.4, 31.5 or 69.6 ng h/ml, respectively and cmax was found to be 1.0, 2.4 and 4.9 ng/ml, respectively. With this s.c. administration protocol, objective antitumour responses were observed in two patients, but there was no partial or complete remission.
Cancer Immunol Immunother 1991
PMID:Pharmacokinetics and biological activity in subcutaneous long-term administration of recombinant interferon-gamma in cancer patients. 175 34

Nine consecutive patients with HCL seen over a period of five years were reviewed. Male: Female ratio was 8:1. Median age at diagnosis was 49 years. Weakness and fatigue (66%) were the commonest presenting symptoms and splenomegaly (66%) was the commonest physical findings. Varying degrees of pancytopenia was the consistent feature in majority of cases. Diagnosis was made on the basis of bone marrow biopsy and characteristic EM picture. Forty-four percent of cases developed serious infection during their clinical course. Gram negative bacilli and fungi were the most frequently isolated organisms. Major sites of infections were pneumonia and septicemia. Splenectomy was carried out in four cases. Rapid recovery of haematological parameters without any significant complication was observed in all these cases. Two patients were treated with alfa-interferon. In both the cases recovery of haematological parameters was slow compared to those under going splenectomy. One patient treated with alfa-interferon died due to infection related complications while the other went into remission.
Indian J Cancer 1991 Sep
PMID:Hairy cell leukaemia. A review of nine cases. 178 82

The present trial was designed to evaluate whether interferon (IFN) combined with standard induction chemotherapy and/or interferon remission maintenance treatment improve treatment results in patients with multiple myeloma. Up to now 89 patients have received IFN plus vincristine/melphalan/cyclophosphamide/prednisolone (VMCP) as induction therapy, and 86 conventional VMCP. The proportion of patients with progressive disease was significantly lower (P less than 0.005) under IFN + VMCP as compared to the VMCP treatment group. Survival times were significantly longer (P less than 0.02) after IFN + VMCP induction therapy than after VMCP alone. In the second phase of this investigation, 33 progression-free myeloma patients were assigned to receive IFN as maintenance therapy, and 41 patients served as untreated controls. Patients maintained with IFN showed a tendency towards increased progression-free survival. Haematological side effects were observed significantly more often in patients receiving IFN, with more severe haematological toxicity in patients on the combined IFN + VMCP regimen and an increased number of patients with mild haematological toxicity in the group maintained with IFN. Other side effects, such as fever and fatigue, remained within tolerable limits. In conclusion, the preliminary results of this current clinical trial indicate significant advantages of combined IFN + VMCP induction treatment in terms of reduced disease progression and prolonged survival and possible benefits of IFN maintenance therapy in patients with multiple myeloma.
Eur J Cancer 1991
PMID:Interferon alfa-2b with VMCP compared to VMCP alone for induction and interferon alfa-2b compared to controls for remission maintenance in multiple myeloma: interim results. 179 76

A phase I trial of Roussel-Uclaf recombinant human interleukin 2 (IL 2) was performed on 31 cancer bearing patients of the Institut Gustave-Roussy, Villejuif, and the Institut Curie, Paris. This study allowed to define a schedule for administration of IL 2 in continuous infusion over 5 day cycles. This schedule is manageable in patients without major visceral failure. It is reproducibly feasible in conventional medical oncology units, without specialized intensive care facilities. Toxicities, although numerous, are acceptable for IL 2 doses below 24,000,000 IU/m2/day. There is a close relationship between secondary effect severity and IL 2 doses received. Main toxicities were: fever with chills, fatigue and general discomfort in 23 patients, nauseas and vomiting in 12, diarrhea in 10 and cutaneous rashes with erythema and dermal vascularitis in 13. One peculiar feature of this study was the minimal occurrence of manifestation related to leaky capillary syndrome prominant in other studies. Oliguria, functional renal failure and edema were observed in only 4 patients with functionally unique kidney. Five patients had severe anemia, 2 grade III thrombocytopenia, 1 grade IV hepatic cytolysis, 4 severe confusion episodes and 2 hypothyroidism with anti-thyroid microsome auto-antibodies. All these toxicities were reversible after withdrawal of IL 2 treatment. During this phase I trial, 3 therapeutic objective responses were observed, all 3 occurring in patients with metastatic melanoma treated with IL 2 doses equal to, or above 16,000,00 IU/m2/d. Recombinant IL 2 Roussel-Uclaf thus can be administered through a simple, manageable and efficient regimen.
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PMID:[Phase I trial of a recombinant human interleukin 2. Results in patients with disseminated solid tumors]. 182 63

Fatigue (stress) fractures are due to increased repetitive stresses. The onset of clinical symptoms and the pain characteristic usually are vague; furthermore the radiographic picture shows lesions of different age and therefore may mimic a pattern typical of bone tumors. While for malignant bone tumors early diagnosis, biopsy and initiation of the appropriate treatment is of importance, the biopsy of a fatigue fracture is not only unnecessary, but also may interfere with the healing process. The value of magnetic resonance imaging in the differential diagnosis between tumors and fatigue fractures has therefore been analysed. Five consecutive cases of fatigue fractures have been evaluated from the onset of symptoms for a mean of 19 month (range 3-45 month) of follow-up. The signal pattern with low intensity in the area of the lesion in T1- and T2-weighted images seen in 2 cases has lead to observe the process under immobilization of the affected limb, while because of an increase of the signal intensity from T1- to T2-weighted images as seen in almost all malignant bone tumors biopsy has been performed in 2 cases. In 1 cases no biopsy but close-meshed clinical examinations were performed although there was an increase of the signal. From these observations we conclude that the MRI in fatigue fractures may either show a 'chronic' type of reaction with low signal intensity allowing for the caution observation while in cases with the rather 'acute' reaction with increased signal biopsy usually cannot be avoided in order not to miss a malignant tumor.
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PMID:[Fatigue fracture as a tumor-simulating lesion. Differential diagnostic delimitation using proton spin tomography]. 183 19


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