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)

In any given population of free-living individuals 65 years of age and older, a substantial proportion (in the range of 6% to 25%) suffers from many of the elements of the syndrome of frailty. Although the syndrome is complex and still lacks a standard definition, there is a growing consensus about the signs and symptoms as well as the pattern of biological correlates that characterize this disorder. Patients who are afflicted with frailty typically exhibit loss of muscle strength, fatigue easily, are physically inactive, and have a slow-and often unsteady-gait, with an increased risk (and fear) of falling. They are likely to have a poor appetite and to have undergone a recent, unintentional loss of weight. Frail individuals are more likely than the nonfrail to experience impaired cognition and depression. They die sooner. Frailty, of course, is frequently complicated by a variety of coexistent illnesses. Among the biological correlates of frailty are sarcopenia (now readily measurable by dual-energy x-ray absorptiometry [DXA]), osteopenia (with an increased susceptibility to fracture), and activation of the inflammatory and coagulation systems, with a rise in inflammatory cytokines and several markers of coagulopathy. Age-dependent changes in a number of hormones also appear to promote the development of frailty in the elderly, particularly via their effects on muscle mass and strength, bone density, and by contributing to activation of the catabolic cytokines. In particular, serum levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) decline progressively during aging, and an association between reduction in the levels of these hormones and the involution of advancing age has been proposed. It is not yet known whether, in comparison with their nonfrail counterparts, frail individuals consistently manifest larger reductions in GH and IGF-1 (and other anabolic hormones). More research is needed before it will be known whether the benefits of administering GH to the frail elderly will outweigh the disadvantages. The poor appetite and weight loss that occur in many frail individuals are likely to be accompanied by a degree of visceral protein depletion (with its attendant morbidity), which can be estimated by making serial measurements of indicators of visceral protein status such as transthyretin (TTR), retinol-binding protein (RBP), and albumin. One characteristic of the frailty syndrome that distinguishes it from the effects of aging per se is the potential reversibility of many of its features. Progressive resistance training is feasible for many elderly individuals-even the oldest old-and, by increasing muscle mass and strength, can ameliorate or reverse important aspects of physical frailty. To the extent that visceral protein depletion has been caused by an inadequate intake of calories and protein, consumption of a more adequate diet can result in betterment of the frail patient's nutritional status, as determined by clinical improvement and favorable changes in TTR, RBP, and albumin.
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PMID:Frailty in the elderly: contributions of sarcopenia and visceral protein depletion. 1457 59

A recombinant enzyme-linked immunosorbent assay (ELISA) followed by a neutralization test (NT) and recombinant immunoblot assay (RIBA) were used for the detection of antibody to hepatitis C virus (anti-HCV) in 71 patients receiving 84 orthotopic liver grafts between 1984 and 1990. Before the liver transplantation (LTX) anti-HCV was present in six of the 71 recipients (8.5%) who were accepted for LTX because of acute or chronic liver failure. After LTX anti-HCV could not be detected in one of the patients, but it was continuously present in the others for more than 12 months. Detectable HCV antibodies were not present in the three patients who underwent LTX because of clinical evidence of fulminant NANB hepatitis. Two of 48 (4.2%) previously HCV seronegative recipients, who survived more than 3 months, seroconverted 9 and 16 months, respectively, after transplantation. The postoperative seroconversion was probably due to the transfer of virus via perioperative blood transfusions. Thus, these liver recipients may be able to respond by producing anti-HCV despite immunosuppressive therapy. None of the seven post-transplant HCV-seropositive patients developed symptoms such as icterus or fatigue, which would suggest the presence of liver insufficiency due to HCV infection. However, two of them had increased transaminase levels and histological signs of mild hepatitis. No significant difference was found in 1-year survival, prothrombin complex, albumin levels or the risk for retransplantation in post-transplant anti-HCV-seropositive patients, compared with those without detectable HCV antibodies (71% vs 69%, respectively). Thus, during the study period of 1-5 years, the clinical course of HCV infection was milder than that reported for hepatitis B infection in liver recipients.
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PMID:Seroprevalence and outcome of hepatitis C in liver transplantation. 1462 69

Daily dialysis have showed excellent results because a higher frequency of dialysis is more physiological and it decreases the fluctuation of liquid, solutes and electrolytes. Improvement of certain causes of anorexia such as postdialysis fatigue, reduction in fluid overload, uremic milieu, medium and large-sized molecule removal could be observed with daily dialysis. The aim of this study was to evaluate nutritional parameters when thrice weekly on-line hemodiafiltration (OL-HDF) were switched to daily OL-HDF. 24 patients have been studied. Eight patients, 6 males and 2 females, mean age of 65.9 +/- 14 years, on thrice weekly 4 to 5 hours OL-HDF were switched to 2 to 2.5 hours six times per week. Dialysis parameters were the same in both periods and only frequency and dialysis time were changed. Other sixteen patients, mean age of 68.4 +/- 14 years, were a control group which dialysis parameters were maintained. Clinical and biochemical outcome were carried out over twelve months. Daily OL-HDF group: Dry weight increased from 67.8 +/- 8 kg at baseline to 68.5 +/- 8 kg after three months, 69.3 +/- 8 kg after six months (NS), 69.5 +/- 8 kg after nine months (p < 0.05) and 70.8 +/- 8 (p < 0.01) after one year. Mean nPCR increased from 0.93 +/- 0.2 g/kg/d on baseline to 1.18 +/- 0.3 after three moths (P < 0.0-5), 1.13 +/- 0.2 after six months (NS), 1.06 +/- 0.2 after nine months (NS) and 1.10 +/- 0.2 after twelve months (NS). There were no significant changes in serum protein, albumin, prealbumin, transferrin, total cholesterol, HDL-c, LDL-c and triglycerides (TG). There were no changes in control group. Mean dry weight was 62.3 +/- 9 kg at baseline and 62.1 +/- 10 kg after one year. Mean nPCR was 0.97 +/- 0.2 g/kg/d on baseline and 1.03 +/- 0.2 g/kg/d after one year. Neither there were changes in serum protein, albumin, transferrin, total cholesterol, HDL-c, LDL-c and TG. Improvement in nutrition status has been observed with the change from thrice weekly OL-HDF to short daily OL-HDF. Increased appetite and protein intake was accompanied by a dry body weight increase of three kg after twelve months.
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PMID:[Improvement of nutritional status in patients with short daily on-line hemodiafiltration]. 1508 59

Plasma proteins in hemodialysis patients display a significant increase in deamidated/isomerized Asx (asparagine and aspartic acid) content, a marker of protein fatigue damage. This has been linked to the toxic effects of hyperhomocysteinemia in uremic erythrocytes; however, treatment aimed at abating homocysteine levels did not lead to significant reductions in plasma protein damage. The hypothesis that lack of reduction in protein damage could be due to protein increased intrinsic instability, as result of interference with the uremic milieu rather than to hyperhomocysteinemia, was put forward. The deamidated/isomerized Asx content of normal plasma incubated with several uremic toxins for 24 h, 72 h, and 7 d was measured, identifying a group of toxins that were able to elicit this kind of damage. Uremic toxins were also incubated with purified human albumin, and dose-response experiments with the two most toxic agents in terms of protein damage (guanidine and guanidinopropionic acid) were carried out. The effect of the hemodialysis procedure on protein damage was evaluated. For investigating also the consequences of these alterations, human albumin was treated in vitro to produce an increase in deamidated/isomerized Asx residues, and the effects of albumin deamidation on protein binding were evaluated. Among the uremic toxins that are able to elicit protein damage, guanidine produced a dose-dependent increase in protein damage. No difference was found after a hemodialysis session. Deamidated albumin shows normal binding capacity to warfarin, salicylic acid, or diazepam but reduced binding to homocysteine. In conclusion, uremic toxins, especially guanidine, display an ability to induce significant protein damage, which can in turn have functional consequences.
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PMID:Plasma protein aspartyl damage is increased in hemodialysis patients: studies on causes and consequences. 1546 80

To investigate rates of bone turnover and calcium homeostasis in Gambian women, we recruited 103 peri- and postmenopausal women, aged 45 to 80+ years and 11 women of reproductive age. Fasting blood was analyzed for plasma osteocalcin, PTH, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], total- and bone-specific alkaline phosphatase. Plasma and urinary calcium, inorganic phosphate, sodium, potassium, creatinine, and albumin and urine free deoxypyridinoline (Dpd) was also measured. Samples from 20 premenopausal and 31 postmenopausal women from Cambridge, UK were analyzed, using the same methodology for comparison. For the Gambian women, peak calcium excretion occurred at around 50 years of age. For women aged > or =45 years, calcium excretion decreased by 3.0% per year of age (SE 1%; P < 0.005). In this age group, 25(OH)D also decreased with age (P < 0.005). Urinary sodium output, pH, and titratable acid output decreased (all P < 0.05) and total alkaline phosphatase (P < 0.005), osteocalcin (P < 0.005), and PTH (P < 0.05) increased with age. Comparisons were made between the following groups of Gambian and British women: premenopausal, early (age 55-64 years)- and late (age 65+ years)-postmenopausal. Gambian women of all ages were lighter (P < 0.001), shorter (P < 0.01), and had higher plasma bone-specific alkaline phosphatase activity (P < 0.05) and higher concentrations of osteocalcin (P < 0.05), PTH (P < 0.001), 1,25(OH)(2)D (P < 0.001), and 25(OH)D (P < 0.001). There were no consistent differences in calcitonin, while urinary free Dpd outputs were lower in the Gambians (P < 0.001). Plasma calcium, phosphate, and albumin (P < 0.01) were significantly lower. Urinary calcium, phosphate, sodium, and potassium excretion were lower, particularly in the postmenopausal group (P < 0.001). Although Gambian urine pH was more acidic, titratable acid output was lower (P < 0.01). These data show that Gambian women with low dietary calcium intakes and good vitamin D status have low urinary calcium excretion and that menopausal changes in calcium and bone metabolism among Gambian women are similar to those seen in other populations. In addition, they demonstrate that Gambian women of all ages have raised plasma PTH and 1,25(OH)(2)D concentrations and raised markers of osteoblast activity. We postulate that high endogenous PTH concentrations may be beneficial to bone health in Gambian women, removing fatigue damage and improving bone quality.
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PMID:Parathyroid hormone and rates of bone formation are raised in perimenopausal rural Gambian women. 1578 Sep 75

The health effects of long-term ingestion of rare earth elements (REEs) on the villagers living in high-REE-background areas in South Jangxi Province, China were studied. Major health complaints from the REE area population included indigestion, diarrhea, abdominal distension, anorexia, weakness, and fatigue, especially after high-fat or high-protein intake. Liver function tests were conducted for adult villagers. Among them, 45 live in a heavy rare earth (HREE) area, 62 in a light rare earth (LREE) area, and 49 in the control area. Test results showed that serum total protein and globulin from both HREE and LREE areas, as well as albumin from the LREE area, were significantly lower (p < 0.01 - 0.01) compared to the results from the control area, whereas albumin from the HREE area showed no significant variance (p > 0.05). The chi-square test showed that Serum-glutamic pyruvic transaminase (SGPT) in both areas were not significant (p > 0.05), whereas the IgM in the HREE area was significantly elevated. It is our conclusion that long-term ingestion of REE affected activities of some digestive enzymes, causing malabsorption and indigestion, and might further lead to a low-protein effect for the villagers in the LREE area. However, the damage to the liver was rather mild. The elevation of IgM was probably the result of stimulation induced by the formation of a large amount of granules as a result of direct binding of REEs to globulin or albumin (combination of REEs with globulin or albumin).
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PMID:Investigation on liver function among population in high background of rare earth area in South China. 1585 27

A controlled cross-linking polymerization system was designed, and soluble chemically cross-linked polyurethane was synthesized using laurylamine, n-octylamine, n-pentylamine, and ethylenediamine chain extenders. The mechanical analysis showed that the polyurethane materials synthesized in this paper have very excellent mechanical properties with a breaking elongation of 1914% and a tensile strength of 4303 N/cm(2). Such good mechanical properties must enable it to have good longevity when used as biomaterials. The polyurethane materials with n-pentylamine and n-octylamine chain extenders show reduced platelet adhesion than that with an ethylenediamine chain extender after sustaining 200 000 times of load cycles, indicating that polyurethanes introduced with an alkyl side chain onto the hard segments keep good antithrombogenic properties after sustaining load cycles. This might be because the hard segments are shielded by the alkyl side chain when the micro-phase-separation structure is destroyed in the repeated deformation of the polyurethane materials. The present investigation reveals that the influence of introducing long alkyl side chains into the backbone of the polyurethane macromolecule has been shown to reduce platelet deposition and to enhance in vitro albumin adsorption. However, in this paper, it has been observed that the polyurethane material introduced with a proper-length alkyl side chain onto the hard segment has the best antithrombogenic properties after the fatigue test.
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PMID:Synthesis and characterization of novel blood-compatible soluble chemically cross-linked polyurethanes with excellent mechanical performance for biomedical applications. 1587 98

Multicentric Castleman disease (MCD) is an atypical lymphoproliferative disorder characterized by systemic lymphadenopathy and constitutional inflammatory symptoms. Dysregulated overproduction of interleukin-6 is responsible for the clinical abnormalities. This multicenter prospective study was undertaken to evaluate the safety and efficacy of a humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody (MRA) in patients with MCD. We report here results of the first 60 weeks of the study enrolling 28 patients. The initial dosing period consisted of 8 infusions of 8 mg/kg MRA administered biweekly. Adjustments in the dose and treatment interval were allowed for each patient in an extension phase after 16 weeks. Within 16 weeks, treatment with MRA consistently alleviated lymphadenopathy and all the inflammatory parameters. Hemoglobin, albumin, and total cholesterol levels, high-density lipoprotein cholesterol values, and body mass index all increased significantly. In addition, fatigue diminished. Chronic inflammatory symptoms were successfully managed over 60 weeks. In 8 (28.6%) patients, the MRA dose was decreased or the treatment interval was extended without exacerbation. Eleven (73.3%) of 15 patients who had received oral corticosteroids before study entry were able to do well on a reduced corticosteroid dose. Most adverse events were mild to moderate in severity. MRA was tolerated well and significantly alleviated chronic inflammatory symptoms and wasting in patients with MCD.
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PMID:Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. 1599 37

Protein-losing gastropathy due to diffuse varioliform gastritis is a rare condition, and its occurrence accompanying ampullary carcinoma is particularly rare. We report here a case of ampullary carcinoma accompanied with protein-losing gastroenteropathy due to diffuse varioliform gastritis. A 39-year-old Japanese woman was admitted to our hospital because of general fatigue and generalized edema. Her total protein level was 3.1g/dL, with an albumin level of 1.4g/dL, and hemoglobin level of 6.9g/dL. Upper gastrointestinal endoscopic examination showed diffuse varioliform gastritis and carcinoma of the papilla of Vater. A diagnosis of protein-losing gastropathy was made based on the results of scintigraphy using technetium 99m-labeled human albumin. Continuous bleeding from ampullary carcinoma caused anemia and deteriorated hypoproteinemia. Pancreaticoduodenectomy was performed for ampullary carcinoma prior to Helicobacter pylori eradication. The tumor was a papillary adenocarcinoma, which had invaded the lamina muscularis propria over the sphincter of Oddi; the resected stomach revealed typical hyperplastic lymphocytic gastritis. H. pylori were detected on microscopic analysis. Scintigraphy after surgery showed no accumulation of the tracer in the bowel. Anemia, hypoalbuminemia and diffuse varioliform gastritis are improved 6 months after surgery and H. pylori eradication, and the patient is currently free from disease.
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PMID:Ampullary carcinoma associated with protein-losing gastropathy due to diffuse varioliform gastritis. 1600 48

Physiological and biochemical responses of skeletal muscle fibres to enhanced neuromuscular activity under conditions of maximum activation can be studied experimentally by chronic low-frequency stimulation of fast muscles. Stimulation-induced changes in the expression pattern of the rabbit fast skeletal muscle proteome were evaluated by two-dimensional gel electrophoresis and compared to the altered isoform expression profile of established transformation markers such as the Ca2+-ATPase, calsequestrin and the myosin heavy chain. Sixteen muscle proteins exhibited a marked change in their expression level. This included albumin with a 4-fold increase in abundance. In contrast, glycolytic enzymes, such as enolase and aldolase, showed a decreased expression. Concomitant changes were observed with marker elements of the contractile apparatus. While the fast isoforms of troponin T and myosin light chain 2 were drastically down-regulated, their slow counterparts exhibited increased expression. Interestingly, mitochondrial creatine kinase expression increased while the cytosolic isoform of this key muscle enzyme decreased. The expression of the small heat shock protein HSP-B5/alphaB-crystallin and the oxygen carrier protein myoglobin were both increased 2-fold following stimulation. The observed changes indicate that the conversion into fatigue-resistant red fibres depends on: (i) the optimum utilization of free fatty acids via albumin transportation, (ii) a rearrangement of the creatine kinase isozyme pattern for enhanced mitochondrial activity, (iii) an increased availability of oxygen for aerobic metabolism via myoglobin transport, (iv) the conversion of the contractile apparatus to isoforms with slower twitch characteristics and (v) the up-regulation of chaperone-like proteins for stabilising myofibrillar components during the fast-to-slow transition process.
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PMID:Differential expression of the fast skeletal muscle proteome following chronic low-frequency stimulation. 1614 47


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