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

An 8-year-old female with a history of back pain and loss of the ability to walk is presented. Transverse myelopathy was considered clinically after assessing magnetic resonance imaging results of the thoracic spine. Acute lymphoblastic leukemia was diagnosed approximately 5 months after the beginning of symptoms. Reviewing the related literature suggests that transverse myelopathy is not uncommon in neoplastic diseases. Children with a disorder of the spinal cord, especially if accompanied with fatigue and anemia, might have transverse myelopathy-associated malignant disease. Transverse myelopathy can be the initial presentation of acute lymphoblastic leukemia.
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PMID:Transverse myelopathy: an initial presentation of acute leukemia. 1151 15

Farnesyl protein transferase inhibitors (FTIs) represent a new class of anticancer agents specifically targeting aberrant biologic processes involved with cellular transformation and malignancy. Originally developed to inhibit tumors by preventing activation of oncogenic ras genes via suppression of their posttranslational farnesylation, their anticancer activity appears to stem from their ability to inhibit farnesylation of various proteins that mediate signal transduction, growth, apoptosis, and angiogenesis. The safety, biologic activity, clinical response, and pharmacokinetics of R115777, a potent, orally active FTI, were recently investigated in a phase I dose-ranging study in patients with acute leukemias. Patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myelogenous leukemia (CML) in blast crisis received R115777 100 mg, 300 mg, 600 mg, 900 mg, or 1,200 mg twice daily for 21 days. Cycles were repeated every 28 to 31 days for up to four cycles. An overall response rate of 29% (10/34 evaluable patients) was observed across all R115777 doses. R115777 was well tolerated; common adverse events included fatigue, increased creatinine, nausea, and neutropenia. Dose-limiting toxicity occurred at 1,200 mg twice daily. Farnesylation of lamin A and HDJ-2, examined as biologic end points, was inhibited by R115777 doses > or = 600 mg twice daily. Pharmacokinetic evaluation suggests that R115777 is concentrated in bone marrow at steady state. The biologic and antitumor activity and favorable tolerability of R115777 support further clinical evaluation alone and in combination therapy in hematologic malignancies.
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PMID:Farnesyl protein transferase inhibitors as targeted therapies for hematologic malignancies. 1152 24

Trismus is a firm closing of the jaw due to tonic spasm of the muscles of mastication from disease or the motor branch of the trigeminal nerve. Trismus may be produced by a variety of reasons such as dental abscess, trauma, following mandibular block with local anesthesia, as a result of radiation to the facial muscles, and patients after chemotherapy. A case of a referral of a six-year-old boy to a dentist from an ENT due to severe limitation in jaw opening is presented. Intraoral examination and panoramic radiograph demonstrated no signs of infection and/or other pathology. After a diagnosis of trismus was made, due to his icteric appearance, the general fatigue and loss of appetite in the last few days, palpated and sensitive lymph nodes in the submandibular and cervical regions, the child was referred for a complete blood count and sedimentation rate. The laboratory and clinical findings resulted in the diagnosis of acute lymphoblastic leukemia (ALL). Dental and oral manifestations of ALL are discussed, and the trismus may be explained by an intensive infiltration of leukemic cells into the deep portion of the contracting muscles of the face. This case emphasizes the importance of physical examination and independent judgement made by dentists, even when patients are referred to them by other members of the medical communities.
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PMID:Trismus in a 6 year old child: a manifestation of leukemia? 1217 25

Bone marrow necrosis (BMN) is a relatively uncommon clinicopathologic entity. The etiology is diverse, and malignancy, especially hematopoietic in origin, is the most common underlying disease of BMN. In this retrospective analysis, cases with BMN were re-evaluated for etiology, histopathologic details, and clinical manifestations. In the last 8 years, 23 cases of BMN were detected among the 1,083 bone marrow (BM) biopsies, and the prevalence was found to be 2.2%. Three of these 23 cases with BMN were children, and 20 cases were in adults. Sixteen of these cases (80%) had underlying malignant disease, and four (20%) had nonmalignant disease. Among the malignant cases, three cases had acute myeloblastic leukemia (AML), four had relapsed Hodgkin's disease (R-HD), one had acute lymphoblastic leukemia (ALL), two had chronic myelocytic leukemia (CML), two had non-Hodgkin's lymphoma (NHL), three had disseminated intravascular coagulation (DIC) associated with metastatic solid tumor, and one had myelodysplastic syndrome/myeloproliferative syndrome (MDS/MPS). Among the nonmalignant cases, two had tuberculosis infection, one had anti-phospholipid syndrome (APS), and one had a history of drug ingestion. The most common symptoms were bone pain, fever, fatigue, and jaundice. The most common laboratory findings were variable and associated with underlying disease, but anemia, leukopenia, thrombocytopenia, and high LDH and alkaline phosphatase levels were detected in the majority of the cases, as was also seen in other series. BMN was graded according to the extent of necrosis in the BM biopsy, and necrosis was extensive in 12 cases, moderate in five cases, and mild in three cases. Increased reticulin was found in 16 cases; four cases had severe, eight had moderate, and four had mild fibrosis, and this was found to be an interesting accompanying finding in BMN. In conclusion malignancy is the most common cause of BMN but some nonmalignant conditions such as tuberculosis and APS may be the underlying cause of BMN.
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PMID:Bone marrow necrosis: clinicopathologic analysis of 20 cases and review of the literature. 1221 Aug 11

It has been reported that autoimmunity might be sometimes transferred from a donor to a recipient following allogenic bone marrow transplantation (allo-BMT). We report a patient to whom Basedow disease was transferred from the donor through an allo-BMT. A 18-year-old man with acute lymphoblastic leukemia, received the allo-BMT from his HLA-identical sister. Two-years later, he developed symptoms of palpitations and general fatigue. He was diagnosed as having Basedow disease because of hyperthyroidism, and high levels of the anti-thyroid stimulating hormone receptor antibody and antithyroid antibody. When he received the allo-BMT, his donor had neither the clinical symptoms of Basedow disease, nor abnormal findings on examination to determine her eligibility as a the donor. We retrospectively assayed anti-thyroid antibodies from their cryopreserved sera, and found the donor's anti-thyroid antibody was positive, while her serum was negative before transplantation. It was apparent that the donor had subclinical Basedow disease. The patient has remained in complete remission without any signs of chronic graft-versus-host disease (GVHD) up till the time of writing. It is believed that an anti-thyroid tissue reactive B-cell clone was transferred from the donor to the patient and commenced to produce antibodies. It is suggested that thorough investigation of the donor's autoimmunity is needed before allo-BMT. If the recipient develops an autoimmune disease after allo-BMT, we should definitely investigate the donor's autoimmunity.
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PMID:[Basedow disease occurring after allogeneic bone marrow transplantation for acute lymphoblastic leukemia]. 1241 87

Lymphomas secondarily involving the breast are uncommon, although they do represent the largest group of tumors metastatic to breast. A 20-year-old female with lymphoblastic lymphoma (LBL) presented here with 3 month history of weight loss, night sweats, fatigue and a mass in her left breast. Her physical examination revealed a left breast mass, lympadenopathy, bilateral pleural effusion and hepatomegaly. WBC count was 17,710/mm3 and LDH was mildly elevated. Breast ultrasound showed a 1.7 cm mass in the inner lower quadrant of left breast. Biopsy of the breast mass showed diffuse infiltration with small, round atypical cells which did not stain with CD20, CD43, CD34, cytokeratine and were positive for CD3. She was diagnosed as leukemic phase of a precursor T-cell LBL and treated with 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), intrathecal methotrexate and cranial radiotherapy, achieving a complete response. She then was started on maintenance therapy. Four months later she returned with CNS involvement and was started on induction treatment. She had a very aggressive course of disease and died only 12 months after diagnosis. Breast involvement is very rarely seen in precursor T-cell LBL/ALL and in this patient occurred secondarily as part of widespread disease.
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PMID:T-cell lymphoblastic lymphoma presenting with a breast mass. 1516 Sep 67

The purpose of this study was to determine dose-limiting toxicities and pharmacokinetics of imatinib in children with refractory or recurrent Philadelphia chromosome-positive (Ph(+)) leukemias. Oral imatinib was administered daily at dose levels ranging from 260 to 570 mg/m(2). Plasma pharmacokinetic studies were performed on days 1 and 8 of course 1. There were 31 children who received 479 courses of imatinib. The most common toxicities encountered, which occurred in less than 5% of courses, were grade 1 or 2 nausea, vomiting, fatigue, diarrhea, and reversible increases in serum transaminases. One patient at the 440-mg/m(2) dose level had dose-limiting weight gain. There were no other first-course dose-limiting toxicities. A maximum tolerated dosage was not defined. Among 12 chronic myeloid leukemia (CML) patients evaluable for cytogenetic response, 10 had a complete response and 1 had a partial response. Among 10 acute lymphoblastic leukemia (ALL) patients evaluable for morphologic response, 7 achieved an M1 and 1 achieved an M2 bone marrow. We observed marked interpatient variability in the pharmacokinetic parameters. In conclusion, we found that daily oral imatinib is well tolerated in children at doses ranging from 260 to 570 mg/m(2). Doses of 260 and 340 mg/m(2) provide systemic exposures similar to those of adults who are treated with daily doses of 400 and 600 mg, respectively.
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PMID:Imatinib mesylate (STI571) for treatment of children with Philadelphia chromosome-positive leukemia: results from a Children's Oncology Group phase 1 study. 1523 74

Somnolence syndrome classically occurs in children after cranial irradiation for acute lymphocytic leukemia. Symptoms include somnolence, fever, nausea and vomiting, and headache. The authors report a 29 year-old female who developed symptoms compatible with the somnolence syndrome after completing radiation therapy for a benign meningioma near the pineal region. Five weeks after completing conformal radiation therapy (54 Gy), she developed profound fatigue, headaches, and 102-degree fevers. Physical examination and routine laboratory work were unrevealing. Imaging was not performed. Prednisone was prescribed and within 1 week her symptoms had largely resolved. This is the first report of the somnolence syndrome after focal radiation therapy. The possible etiology of the somnolence syndrome is discussed.
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PMID:Somnolence syndrome after focal radiation therapy to the pineal region: case report and review of the literature. 1657 37

Imatinib and other Abl tyrosine kinase inhibitors (TKIs), such as dasatinib and nilotinib, have significantly improved the outcome of patients with chronic myeloid leukemia. Imatinib and dasatinib are currently Food and Drug Administration (FDA) approved, and nilotinib is expected to gain FDA approval soon. In addition, several other Abl TKIs are being evaluated in various clinical trials. Imatinib has also shown efficacy in the therapy of gastrointestinal stromal tumors, Philadelphia chromosome-positive acute lymphocytic leukemia and hypereosinophilic syndrome. Because of their efficacy, more patients will receive Abl TKIs for a longer period of time. Imatinib was FDA approved after a short follow-up because of its exceptional efficacy and safety profile. The most common adverse events reported included fluid retention, fatigue, diarrhea, and muscle cramps. With longer follow-up, issues related to the long-term use of imatinib have been discussed. Our aim is to review the emerging safety issues of Abl TKIs after a longer follow-up.
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PMID:Emerging safety issues with imatinib and other Abl tyrosine kinase inhibitors. 1738 19

Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor active clinically in cutaneous T-cell lymphoma and preclinically in leukemia. A phase 1 study was conducted to evaluate the safety and activity of oral vorinostat 100 to 300 mg twice or thrice daily for 14 days followed by 1-week rest. Patients with relapsed or refractory leukemias or myelodysplastic syndromes (MDS) and untreated patients who were not candidates for chemotherapy were eligible. Of 41 patients, 31 had acute myeloid leukemia (AML), 4 chronic lymphocytic leukemia, 3 MDS, 2 acute lymphoblastic leukemia, and 1 chronic myelocytic leukemia. The maximum tolerated dose (MTD) was 200 mg twice daily or 250 mg thrice daily. Dose-limiting toxicities were fatigue, nausea, vomiting, and diarrhea. Common drug-related adverse experiences were diarrhea, nausea, fatigue, and anorexia and were mild/moderate in severity. Grade 3/4 drug-related adverse experiences included fatigue (27%), thrombocytopenia (12%), and diarrhea (10%). There were no drug-related deaths; 7 patients had hematologic improvement response, including 2 complete responses and 2 complete responses with incomplete blood count recovery (all with AML treated at/below MTD). Increased histone acetylation was observed at all doses. Antioxidant gene expression may confer vorinostat resistance. Further evaluation of vorinostat in AML/MDS is warranted.
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PMID:Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes. 1796 10


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