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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mature, circulating mammalian erythrocytes have a finite lifespan. The molecular mechanism that determines removal of cells from the circulation remains unknown, but probably involves recognition of senescence antigens by phagocytes, either directly or via an antibody/complement-mediated pathway. It has been proposed that the major senescence antigen in aged erythrocytes is derived from the band 3 protein, the main transmembrane glycoprotein in erythrocytes. Other possible mechanisms for red cell aging include mechanical fatigue, ATP depletion, calcium accumulation, and the generation of reactive oxygen species (ROS). ROS, which damage proteins and initiate lipid peroxidation, can be generated either inside erythrocytes through the hemoglobin oxidation pathway or outside (eg, by stimulated macrophages). The ROS theory of red cell aging has been widely accepted, yet it lacks direct supporting evidence. To test this hypothesis, two critical techniques have been established in this laboratory. First, we determine the lifespan of erythrocytes in vivo using a fluorescent cell labeling technique. Second, transgenic mice have been produced which express high levels of the human antioxidant enzymes, superoxide dismutase and glucose-6-phosphate dehydrogenase, in their erythrocytes. These two techniques will be very useful for the evaluation of the free radical theory of red cell aging.
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PMID:Free radical theory of erythrocyte aging. 934 76

The purpose of this study was to compare the responses of selected hormonal, immunological, and hematological variables in athletes showing symptoms of overreaching with these variables in well-trained athletes during intensified training. Training volume was progressively increased over 4 wk in 24 elite swimmers (8 male, 16 female); symptoms of overreaching were identified in eight swimmers based on decrements in swim performance, persistent high ratings of fatigue, and comments in log books indicating poor adaptation to the increased training. Urinary excretion of norepinephrine was significantly lower (P < 0.05, post hoc analysis) in overreached (OR) compared with well-trained (WT) swimmers throughout the 4 wk. There were no significant differences between OR and WT swimmers for other variables including: concentrations of plasma norepinephrine, cortisol, and testosterone, and the testosterone/cortisol ratio; peripheral blood leukocyte and differential counts, neutrophil/lymphocyte ratio, and CD4/CD8 cell ratio; serum ferritin and blood hemoglobin concentrations, erythrocyte number, hematocrit, and mean red cell volume (MCV). MCV increased significantly over the 4 wk in both groups, suggesting increased red blood cell turnover. These data show that, of the 16 hormonal, immunological, and hematological variables measured, urinary norepinephrine excretion appears to be the only one to distinguish OR from WT swimmers during short-term intensified training. Low urinary norepinephrine excretion was observed 2 to 4 wk before the appearance of symptoms of overreaching, suggesting the possibility that neuroendocrine changes may precede, and possibly contribute to, development of the overreaching/overtraining syndromes.
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PMID:Hormonal, immunological, and hematological responses to intensified training in elite swimmers. 943 98

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

Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines in vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day.
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PMID:Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors. 953 30

Medullary cystic disease of the kidney is characterized by progressive tubulointerstitial disease with medullary cyst formation and secondary glomerular sclerosis. We treated a patient with chronic renal failure and investigated the family history of renal disease. The patient, an 18-year-old woman, was admitted due to poor appetite and fatigue for several months. Findings on physical examination were normal except for a pale conjunctiva. Urinalysis revealed only mild proteinuria with clear sediment. The hemogram showed normocytic normochromic anemia with hemoglobin 86 g/L. The patient was azotemic and her creatinine clearance rate was 10.7 mL/min. Renal sonography showed contraction of both kidneys with a marked increase in cortical echogenicity. One small cyst was found in the medullary area. Computed tomography (CT) and magnetic resonance imaging revealed several medullary cysts. Percutaneous renal biopsy showed focal and periglomerular sclerosis, marked tubular atrophy, and interstitial fibrosis. Ten of her family members were examined for renal function, and by sonography and CT. Five had medullary cysts, and three of the five showed abnormal renal function. Medullary cystic disease should be considered in the differential diagnosis of patients with renal disease and a positive family history.
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PMID:Medullary cystic disease: a family study. 954 73

An early phase II clinical study of S-1 in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group (Breast Cancer Working Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg (dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty-eight patients were enrolled, 27 were eligible for the study, and 25 were evaluable for efficacy. Four complete responses and seven partial responses were obtained, and the response rate was 40.7% (11/27) [ninety percent confidence interval for this response was 26.7-56.4%]. The major adverse reactions observed were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7% (11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia 55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The results suggested that the efficacy and safety of S-1 were effective against advanced or recurrent breast cancer. The objective of study judged should be investigated in a late phase II clinical study.
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PMID:[An early phase II clinical study of S-1 in patients with breast cancer. S-1 Cooperative Study Group (Breast Cancer Working Group)]. 964 19

Anemia is a multi-symptom syndrome involving both physical and emotional problems that can be evaluated for their impact on quality of life. Fatigue is the cardinal symptom of anemia, reported by three of four cancer patients using the general version of the Functional Assessment of Cancer Therapy (FACT-G) questionnaire. A subscale of the FACT-G, consisting of the FACT-Fatigue (FACT-F) and the FACT-Anemia (FACT-An), has been developed to specifically address this problem. The FACT-F is comprised of the FACT-G plus 13 questions related to fatigue, while the FACT-An is comprised of the FACT-F plus an additional set of seven miscellaneous (non-fatigue) questions relevant to anemia in cancer patients. The FACT-An subscale was initially validated in a cohort of 50 cancer patients. Tests of internal consistency and stability confirmed the reliability of the fatigue component, as well as that of the FACT-G (27 items), the FACT-F (FACT-G plus 13 fatigue items), and the FACT-An (FACT-G plus 20 anemia subscale items) measurement systems. Quality of life scores on these FACT scales significantly decline as patient performance status worsens, and the scales correlate well with other questionnaires (Profile of Mood States and Piper Fatigue Scale) purported to measure the same thing. The scores on the FACT-An subscale also clearly differentiate between patients with low and high hemoglobin levels. Low hemoglobin levels are associated with greater fatigue, poorer overall quality of life, and decreased ability to work (beyond that related directly to fatigue). Interventions that reverse fatigue and other anemia-related symptoms should have a positive effect on quality of life.
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PMID:Factors influencing quality of life in cancer patients: anemia and fatigue. 967 30

Anemia is common in patients infected with the human immunodeficiency virus (HIV). The etiology is often multifactorial and may include the HIV infection itself, opportunistic infections, cancer, medications (particularly zidovudine and sulfa-containing drugs), or anemia of chronic disease. Epoetin alfa therapy may play a supportive role in some HIV-infected patients by increasing hemoglobin, decreasing fatigue, and reducing the need for exposure to red blood cell transfusions. A large, placebo-controlled trial in the United States for anemic patients with the acquired immunodeficiency syndrome taking zidovudine demonstrated a statistically significant improvement in hematocrit in patients treated with epoetin alfa compared with placebo. Transfusion requirements decreased in epoetin alfa-treated patients over a 3-month period compared with placebo with a trend toward improvement in quality of life. Epoetin alfa was effective, however, only in patients whose pretreatment erythropoietin levels were less than 500 mU/mL. These advantages of epoetin alfa treatment may become especially important as HIV becomes more of a chronic disease, with the concern that red blood cell transfusion may accelerate progression of HIV.
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PMID:Experience with epoetin alfa and acquired immunodeficiency syndrome anemia. 967 34

Cisplatin is a known cause of hemolytic uremic syndrome (HUS). The acute, fulminant form of cisplatin-induced HUS is almost always fatal. We present a 67-year-old Hispanic woman who was treated with cisplatin for squamous cell carcinoma of the tongue. Three days after receiving the treatment, she presented with increasing fatigue, decreased urine output, and confusion. Physical examination was remarkable for tachycardia of 130 beats/min, peripheral edema, and mental obtundation. Laboratory investigations showed a white cell count of 5,500/microL, hemoglobin level of 9.6 g/dL, hematocrit of 29.6%, and platelet count of 13,000/microL. Schistocytes were present on peripheral smear. Screening for disseminated intravascular coagulation was negative. Serum chemistry values included blood urea nitrogen 111 mg/dL, creatinine 3.8 mg/dL, and lactate dehydrogenase (LDH) 927 IU. The patient underwent hemodialysis and therapeutic plasma exchange (TPE), using fresh frozen plasma (FFP). Dialysis was no longer required after the fifth day. TPE was performed daily until the platelet count normalized on the 13th day, after which intertreatment intervals were extended until normalization of LDH levels on the 50th day. We conclude that the normally fatal, fulminant form of cisplatin-induced HUS can be successfully treated with standard TPE, using FFP replacement.
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PMID:Successful treatment of cisplatin-induced hemolytic uremic syndrome with therapeutic plasma exchange. 970 19

This study assessed correlates of fatigue and the efficacy of testosterone therapy as a treatment for fatigue in men with symptomatic HIV and clinical hypogonadism. We conducted a 12-week open trial of testosterone for HIV+ men with clinical hypogonadism (low libido plus at least one of the associated symptoms of depressed mood, fatigue, and weight loss), CD4 count below 400 cells/cu.mm, and serum testosterone level below 500 ng/dl. 108 men entered the trial; 50% were nonwhite and 72% had an AIDS diagnosis. Baseline correlates of fatigue, as measured by the self-report Chalder Fatigue Scale (CFS), included elevated laboratory values (hematocrit, hemoglobin), lower overall physical functioning, greater psychological distress, and reduced quality of life. Sixty-six of 72 men who presented with fatigue completed the trial, with 52 (79%) rated as responders (much improved energy level) by the study doctor. Fatigue declined significantly among responders, but not nonresponders.
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PMID:Testosterone as a treatment for fatigue in HIV+ men. 971 99


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