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)

Apart from its anti-inflammatory activity, which has been used for the treatment of active Crohn's disease, thalidomide is also a potent inhibitor of angiogenesis. We therefore studied the effect of thalidomide in six patients with severe recurrent intestinal bleeding refractory to standard treatment (three patients with Crohn's disease (CD), three patients with obscure intestinal bleeding; mean of 56 blood transfusions within the last 24 months). Bleeding stopped within two weeks after the start of thalidomide in all patients. Haemoglobin normalised without further transfusions for the whole observation period (mean follow up 33 months) while patients needed a mean of 2.2 (CD) and 3.1 (obscure bleeding) blood units/month in the 12 months before treatment. After three months of thalidomide therapy, serum levels of vascular endothelial growth factor were strongly suppressed compared with pretreatment levels. (CD 818 (82) v 129 (86) pg/ml; obscure bleeding 264 (68) v 50 (25) pg/ml). All six patients reported transient fatigue. Peripheral neuropathy was observed in one patient with CD after nine months and was reversible after lowering the dose to 100 mg daily. These results indicate that thalidomide might be useful for patients with otherwise refractory intestinal bleeding.
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PMID:Thalidomide for treatment of severe intestinal bleeding. 1501 59

Intolerance of gluten, resposible for Coeliac disease, is essentially shown by an auto-immune enteropathy, even if the cutaneous manifestation (herpetiform dermatitis) and perhaps certain neurological signs (cerebral syndrome, peripheral neuropathy) may be independent as well as associated with the intestinal illness. This affection is of immunological nature, occuring in a genetic field that predisposes to the illness (familial form: concordance of 70% in homozygote twins; 90% of patients show an HLA molecule of type DQ2, DQ8 in almost all the other cases. The exogenous factor is the gluten content contained in wheat, rye and barley, more precisely by the intermediary "the prolamines" which are the "reactive" element that induces a the same time an inflammatory reaction of type TH11 locally (expressed by the histological aspect of a duodenal biopsy evolving as villous atrophy) and a humoral response with production of anti-gliadine and anti-transglutaminase antibodies (the role of the latter enzyme is intervention in the local transformation of antigens to make them antigenic). It is an illness of adults as well as children and this point must now be emphasized. Recent epidemiological studies insist on a high prevalence (1/300 in Europe). Clinical expression, at the start very polymorphic and so misleading, before the appearance of the more classical signs of malabsorption and development, always feared, towards a lymphoma. These signs are haematological (anemia of various types, hyper platelets by hyposplenism, haemorrhagic signs) cutaneous (herpetiform dermatitis, cutaneous vasculitis) mucosal (aphtose), hepatic (cytolysis), neurophysical (fatigue, troubles of behaviour, cerebral syndrome, neuropathy) and osteo-articulitis (osteopenia, arthralgias, diffuse pains). The association of certain auto-immune illnesses must be emphasized (diabetes, Hashimoto thyroiditis, Gougerot disease, primitive biliary cirrhosis). To think early of the possibility of intolerance to gluten, is to give the means of a very easy diagnosis (measurement of anti-gliadin, anti-endomysium and anti-transglutaminase, and secondarily duodenal biopsy if necessary), and it is early elimination of gluten food which will make the various clinical manifestations disappear and so prevent the risk of evolution to a tumoral pathology.
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PMID:[A great imitator for the allergologist: intolerance to gluten]. 1513 80

Thalidomide has re-emerged as a novel antineoplastic agent with immunomodulatory and antiangiogenic activities. In the early sixties, it was withdrawn from the market after its infamous association with congenital abnormalities that left about 10,000 children affected world-wide. With strict regulations and precautions, thalidomide is now approved by the FDA for the treatment of erythema nodosum leprosum. Its role in cancer therapy is promising, with clinical trials in the past 5 years showing significant activity in multiple myeloma. Several trials are ongoing in other malignancies, such as myelodysplastic syndrome, agnogenic myeloid metaplasia, renal cell carcinoma, and prostate cancer. The major toxicities of thalidomide are birth defects, sensorimotor peripheral neuropathy, somnolence, rash, fatigue, and constipation. Less common side effects include deep venous thrombosis, Stevens-Johnson syndrome, elevated liver enzymes, malaise, and peripheral edema. The incidence and severity of adverse events are related to dose and duration of therapy. Doses of the drug of 200 mg/day or less are usually well tolerated. In this review, we will discuss the incidence and management of the side effects of thalidomide and the precautions and interventions needed to minimize the toxicities of this drug.
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PMID:Management of thalidomide toxicity. 1533 75

Thalidomide has been proved to play an important role in rescue treatment of patients with refractory/relapsed multiple myeloma (MM). However, thalidomide therapy is associated with numerous side effects, mainly somnolence, constipation, fatigue or peripheral neuropathy. We report three patients diagnosed with MM and treated with thalidomide as salvage therapy who developed severe renal failure when they received aminoglycoside antibiotics. This observation suggests that thalidomide can potentiate nephrotoxicity of aminoglycoside antibiotics in patients with MM.
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PMID:Aminoglycoside-associated severe renal failure in patients with multiple myeloma treated with thalidomide. 1537 Feb 32

Multiple myeloma (MM), a malignancy of the plasma cells, accounts for an estimated 14% of all newly diagnosed hematologic malignancies. Advances in chemotherapy and stem cell transplantation have improved survival rates, but MM remains incurable. Bortezomib (Velcade, Millennium Pharmaceuticals, Inc., Cambridge, MA), a first-in-class proteasome inhibitor, has been approved for patients with MM who have received at least two prior treatments and have demonstrated disease progression on the most recent one. During clinical trials, most side effects were manageable with standard interventions. The most common toxicities were asthenic conditions (fatigue, malaise, and weakness), gastrointestinal disturbances (nausea, vomiting, diarrhea, and constipation), thrombocytopenia, peripheral neuropathy, pyrexia, and anemia. Supportive therapies and strategies for side-effect management can prevent worsening of these symptoms, thereby avoiding dose reductions and treatment delays. Oncology nurses play a key role in ensuring the proper and safe administration of bortezomib and often are the first to identify the signs of side effects. Patient education about anticipated side effects and close monitoring of patients can lead to symptom management interventions that are essential to patient comfort and safety.
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PMID:Bortezomib, a newly approved proteasome inhibitor for the treatment of multiple myeloma: nursing implications. 1551 81

Concurrent chemoradiotherapy plays an important role in the treatment of unresectable NSCLC. This phase II study was conducted to evaluate the efficacy and toxicity of paclitaxel (PTX) and carboplatin (CBDCA) at a recommended dose, based on other previous phase I studies. Twenty-two unresectable stage III NSCLC patients participated in this trial. Of those 22 patients, 19 were evaluable, with a median age of 57 (with ages ranging between 42 and 74), in stages IIIA/IIIB: 6/13. Every patient displayed adequate organ functions. Treatment consisted of a 1-hour i.v. infusion of 50 mg/m2 of PTX followed by a half-hour infusion of CBDCA AUC 2 administered weekly concurrently with radiation treatment, every first day of those weeks in which the patient underwent radiotherapy. Concurrent thoracic radiation therapy was performed in daily doses of 2 Gy to a total dose of 66 Gy over a period of 6.5 weeks. After completion of chemoradiotherapy, consolidation chemotherapy was administered via a 3-hour i.v. infusion of 175 mg/2 PTX on days 1 and 22, in combination with a 1-hour i.v. infusion of CBDCA AUC 6 on days 1 and 22, q 4 weeks for 4 cycles. The overall response rate was 78.9% (95% CI: 62-87.7) with 5 CR (26.3%), 10 PR (52.6%), 2 SD (15.8%), and 1 PD (5.3%). The median survival rate of the patients was 13.9 months, and the 1-year survival rate was 65.1%. Toxicity was moderate: grade 2 neutropenia was seen in 8, and grade 3 neutropenia in 5 patients. Grade 2 thrombocytopenia was seen in 3 patients, and grade 3 thrombocytopenia was not observed. Nonhematologic toxicities were moderate: esophagitis was the most common, and significant toxicity was noted in this study (89.4%). Grade 1 asthenia/fatigue was observed in 5, and grade 2 asthenia/fatigue in 3 patients; furthermore, grade 1 peripheral neuropathy was seen in 4 of the cases and grade 2 peripheral neuropathy in 3 of the cases. Concurrent chemoradiotherapy with weekly PTX/CBDCA, followed by consolidation chemotherapy with the same regimen in patients with stage III unresectable NSCLC is feasible and well tolerated.
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PMID:Preliminary results of a phase II study of weekly paclitaxel (PTX) and carboplatin (CBDCA) administered concurrently with thoracic radiation therapy (TRT) followed by consolidation chemotherapy with PTX/CBDCA for stage III unresectable non-small-cell lung cancer (NSCLC). 1557 39

Proteasome inhibitors, a novel class of chemotherapeutic agents, enhance the antitumor efficacy of anthracyclines in vitro and in vivo. We therefore sought to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of bortezomib and pegylated liposomal doxorubicin (PegLD). Bortezomib was given on days 1, 4, 8, and 11 from 0.90 to 1.50 mg/m2 and PegLD on day 4 at 30 mg/m2 to 42 patients with advanced hematologic malignancies. Grade 3 or 4 toxicities in at least 10% of patients included thrombocytopenia, lymphopenia, neutropenia, fatigue, pneumonia, peripheral neuropathy, febrile neutropenia, and diarrhea. The MTD based on cycle 1 was 1.50 and 30 mg/m2 of bortezomib and PegLD, respectively. However, due to frequent dose reductions and delays at this level, 1.30 and 30 mg/m2 are recommended for further study. Pharmacokinetic and pharmacodynamic studies did not find significant drug interactions between these agents. Antitumor activity was seen against multiple myeloma, with 8 of 22 evaluable patients having a complete response (CR) or near-CR, including several with anthracycline-refractory disease, and another 8 having partial responses (PRs). One patient with relapsed/refractory T-cell non-Hodgkin lymphoma (NHL) achieved a CR, whereas 2 patients each with acute myeloid leukemia and B-cell NHL had PRs. Bortezomib/PegLD was safely administered in this study with promising antitumor activity, supporting further testing of this regimen.
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PMID:Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies. 1562 43

POEMS (Crow-Fukase) syndrome is a rare plasma cell lymphoproliferative disorder associated with polyneuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal (M) gammopathy and skin (S) abnormalities. The latter are usually not specific and include hyperpigmentation, hypertrichosis, cutaneous angioma and skin-thickening. A 45-year-old Italian woman was admitted to hospital because of muscle weakness, marked fatigue and paresthesia of the upper and lower extremities. Two and a half years earlier, a POEMS syndrome had been diagnosed on the basis of a history of organomegaly and mild lymphadenopathy, IgA-lambda monoclonal gammopathy, hypothyroidism, severe lower and upper limb sensory-motor peripheral neuropathy and a single osteosclerotic lesion in the left humerus. Eight weeks later, she developed skin lesions bioptically shown to be due to calciphylaxis-induced cutaneous vasculitis. To our knowledge, this is the first case of POEMS syndrome with this peculiar type of vasculitis. The absence of predisposing conditions, namely renal failure, hyperparathyroidism or clotting disorders renders the pathogenetic mechanism(s) of this severe type of vasculitis more intriguing.
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PMID:Calciphylaxis in a patient with POEMS syndrome without renal failure and/or hyperparathyroidism. A case report. 1567 10

Amyloidosis is an uncommon plasma-cell dyscrasia with an incidence of eight patients per million per year. It is often difficult to recognize because of the myriad symptoms and vague nature of the clinical presentation. Symptoms include fatigue, dyspnea, edema, paresthesias, and weight loss. Clinical syndromes at presentation include nephrotic-range proteinuria with or without renal insufficiency, cardiomyopathy, hepatomegaly, symptomatic peripheral neuropathy, and autonomic failure. Recent advances have occurred in evaluation of patients by using the free light chain assay and new prognostic assessments with cardiac biomarkers. Newly developed therapeutic strategies, involving high-dose and intermediate-dose chemotherapy, have evolved in the last 3 years. This paper reviews a diagnostic pathway clinicians can use to diagnose the disorder, assess a patient's prognosis, and logically plan a therapeutic strategy.
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PMID:Amyloidosis. 1602 46

The fibromyalgia syndrome (FM) seems an unlikely candidate for classification as a neuropathic pain. The disorder is diagnosed based on a compatible history and the presence of multiple areas of musculoskeletal tenderness. A consistent pathology in either the peripheral or central nervous system (CNS) has not been demonstrated in patients with FM, and they are not at higher risk for diseases of the CNS such as multiple sclerosis or of the peripheral nervous system such as peripheral neuropathy. A large proportion of FM sufferers have accompanying symptoms and signs of uncertain etiology, such as chronic fatigue, sleep disturbance, and bowel/bladder irritability. With the exception of migraine headaches and possibly irritable bowel syndrome, the accompanying disorders are clearly not neurological in origin. The impetus to classify the FM as a neuropathic pain comes from multiple lines of research suggesting widespread pain and tenderness are associated with chronic sensitization of the CNS. An examination of how the term neuropathic pain is defined reveals a conceptual split into 2 partially overlapping groups of disorders: those with demonstrable pathology in the nervous system and those characterized primarily by enduring dysfunction in the nervous system. Requiring demonstrable pathology in the nervous system in the definition of neuropathic pain is the traditional approach. The expansion of the definition to require only enduring nervous system dysfunction is less palatable because it opens the classification to many disorders of uncertain etiology, including complex regional pain syndrome. As it is uncertain which of the many different chronic pain syndromes include an enduring component of central sensitization, restricting the term "neuropathic pain" to those disorders with a primary etiology clearly related to the peripheral or CNS is prudent and consistent with clinical practice.
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PMID:Is fibromyalgia a neuropathic pain syndrome? 1607 59


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