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)

Despite an abundance of preclinical data, relatively little is known regarding the efficacy of DNA vaccination in humans. Here, we present results from a dose-escalation clinical trial of a dual expression plasmid encoding carcinoembryonic antigen (CEA) and hepatitis B surface antigen (HBsAg) in 17 patients with metastatic colorectal carcinoma. CEA was selected as a prototypic tumor-associated self-antigen, and the HBsAg cDNA was included as a positive control for immune response to the DNA vaccine without relying upon breaking tolerance to a self-antigen. Groups of 3 patients received escalating single i.m. doses of the DNA vaccine at 0.1, 0.3, and 1.0 mg. Subsequent groups of 3 patients received three repetitive 0.3- or 1.0-mg doses at 3-week intervals. A final group of 2 patients received three repetitive 2.0 mg doses at 3-week intervals. Toxicity was limited to transient grade 1 injection site tenderness, fatigue, and creatine kinase elevations, each affecting a minority of patients in a non-dose-related manner. Repetitive dosing of the DNA vaccine induced HBsAg antibodies in 6 of 8 patients, with protective antibody levels achieved in four of these patients. CEA-specific antibody responses were not observed, but 4 of 17 patients developed lymphoproliferative responses to CEA after vaccination. No objective clinical responses to the DNA vaccine were observed among this population of patients with widely metastatic colorectal carcinoma. Nevertheless, this pilot trial has provided encouraging human immune response data in support of this vaccine technology.
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PMID:Safety and immunogenicity of a DNA vaccine encoding carcinoembryonic antigen and hepatitis B surface antigen in colorectal carcinoma patients. 1223 17

The purpose of the present study was to examine the acute and long-term fatigue effects of exhausting stretch-shortening cycle (SSC) exercise on the stiffness of ankle and knee joints. Five subjects were fatigued on a sledge apparatus by 100 maximal rebound jumps followed by continuous submaximal jumping until complete exhaustion. Neuromuscular fatigue effects were examined in submaximal hopping (HOP) and in maximal drop jumps (DJ) from 35 (DJ35) and 55 cm (DJ55) heights on a force plate. Additional force and reflex measurements were made using an ankle ergometer. Jumping tests and ankle ergometer tests were carried out before, immediately after, 2 h (2H), 2 days and 7 days (7D) after the SSC exercise. Kinematics, force and electromyography (EMG) recordings were complemented with inverse dynamics, which was used to calculate joint moments. The quotient of changes in joint moment divided by changes in joint angle was used as a value of joint stiffness (JS). In addition, blood lactate concentrations and serum creatine kinase activities were determined. The exercise induced a clear decrease in knee joint stiffness by [mean (SD)] 29 (13)% (P < 0.05) in HOP, 31 (6)% (P < 0.05) in DJ35 and 34 (14)% (P < 0.05) in DJ55. A similar trend was observed in the ankle joint stiffness with significant post-exercise reductions of 22 (8)% (P < 0.05) in DJ35 and of 27 (19)% (P < 0.05) at 2H in DJ55. The subsequent recovery of JS was slow and in some cases incomplete still at 7D. Generally, all the EMG parameters were fully recovered by 2H, whereas the force recovery was still incomplete at this time. These data indicate that the immediate reduction in JS was probably related to the effects of both central (neural) and peripheral (metabolic) fatigue, whereas the prolonged impairment was probably due to peripheral fatigue (muscle damage).
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PMID:Acute and prolonged reduction in joint stiffness in humans after exhausting stretch-shortening cycle exercise. 1243 77

A well-documented observation after eccentric exercise is a reduction in maximal voluntary force. However, little is known about the ability to maintain maximal isometric force or generate and maintain dynamic peak power. These aspects of muscle function were studied in seven participants (5 males, 2 females). Knee extensor isometric strength and rate of fatigue were assessed by a sustained 60 s maximal voluntary contraction at 80 degrees and 40 degrees knee flexion, corresponding to an optimal and a shortened muscle length, respectively. Dynamic peak power and rate of fatigue were assessed during a 30 s Wingate cycle test. Plasma creatine kinase was measured from a fingertip blood sample. These variables were measured before, 1 h after and 1, 2, 3 and 7 days after 100 repetitions of the eccentric phase of the barbell squat exercise (10 sets x 10 reps at 80% concentric one-repetition maximum). Eccentric exercise resulted in elevations in creatine kinase activity above baseline (274+/-109 U x l(-1); mean +/- s(x)) after 1 h (506+/-116 U x l(-1), P < 0.05) and 1 day (808+/-117 U x l(-1), P < 0.05). Isometric strength was reduced (P < 0.05) for 7 days (35% at 1 h, 5% at day 7) and the rate of fatigue was lower (P < 0.05) for 3 days at 80 degrees and for 1 day at 40 degrees. Wingate peak power was reduced to a lesser extent (P < 0.05) than isometric strength at 1 h (13%) and, although the time course of recovery was equal, the two variables differed in their pattern of recovery. Eccentrically exercised muscle was characterized by an inability to generate high force and power, but an improved ability to maintain force and power. Such functional outcomes are consistent with the proposition that type II fibres are selectively recruited or damaged during eccentric exercise.
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PMID:Maximal-intensity isometric and dynamic exercise performance after eccentric muscle actions. 1247 4

The aim of this study was to evaluate myofibrillar creatine kinase (CK) activity and to quantify the substrate channelling of ATP between CK and myosin ATPase under different pH conditions within the integrity of myofibrils. A pure myofibrillar fraction was prepared using differential centrifugation. The homogeneity of the preparation and the purity of the fraction were confirmed microscopically and by enzymatic assays for contaminant enzyme activities. The specific activity of myofibrillar CK reached 584 +/- 33 nmol PCr min(-1) mg(-1) at pH 6.75. Two methods were used to detect CK activity: (1) measurement of direct ATP production, and (2) measurement of PCr consumption. This method of evaluation has been tested in experiments with isolated creatine kinase. No discrepancy in CK activity between the methods was observed in the pH range tested (6.0-7.5). However, the same procedures resulted in a significant discrepancy between the amounts of reacted PCr and produced ATP within the pure myofibrillar fraction. This discrepancy represents the portion of ATP produced by the CK reaction, which is preferentially channelled to the myosin ATPase before diffusing into the bulk solution. The maximum evaluated difference reached 42.3 % at pH 6.95. The substrate channelling between myofibrillar-bound CK and myosin ATPase was evaluated under various pH levels within the physiological range and it reached a maximum value in a slightly acidic environment. These results suggest that ATP/ADP flux control by the CK system is more important at lower pH, corresponding to the physiological state of muscle fatigue.
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PMID:Substrate channelling in a creatine kinase system of rat skeletal muscle under various pH conditions. 1252 49

The purpose of the present study was to investigate the fatigue effect of repeated exhaustive stretch-shortening cycle (SSC) exercise on concentric muscle function. Ten healthy male subjects performed SSC exercise [92 (30) jumps] on a special sledge apparatus. Exhaustion occurred on average within 3 min. A squat jump (SJ) test utilizing a concentric-only action was performed immediately before and after the SSC exercise, and then 10 min, 20 min, 2 days and 4 days later. In addition, a drop jump (DJ) test using an SSC was also performed immediately before and 20 min after the SSC exercise, and 2 days and 4 days later. During jump tests, lower limb joint moment, power, and work contributions were analyzed by using the kinetic and kinematic data. The fatigue exercise was characterized by a relatively high blood lactate concentration [7.2 (0.8) mmol x l(-1)] and a 2-day delayed increase in serum creatine kinase activity [486 (300) U x l(-1)]. SJ performance decreased markedly immediately after the SSC exercise (P<0.05) and then recovered within 10 min. In contrast, DJ performance and knee joint contribution showed a delayed decrease 2 days after the SSC exercise bout. The surface electromyographic (EMG) activity of the lower limb muscles showed no obvious change in the SJ in comparison to the DJ, although in the latter there was a delayed decrease of knee extensor EMG during the pre-activation and braking phases. The results suggest that isolated concentric muscle function is affected mainly by acute metabolic fatigue after SSC exercise. During a follow-up period after the exercise, changes in hip and knee joint contribution in SJ showed a different recovery pattern compared to those in eccentric DJ. It could be suggested that exhaustive SSC exercise would mainly influence the relative power-work balance between the hip and knee joints during the eccentric phase of SSC. Thus different motor control strategies may account for the distinctive fatigue responses observed in SJ and DJ.
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PMID:Exhausting stretch-shortening cycle (SSC) exercise causes greater impairment in SSC performance than in pure concentric performance. 1256 Sep 51

Primary hypothyroidism is a chronic and insidious disease caused by failure of thyroid hormone production. We observed a 38-year-old woman admitted to our hospital due to progressive proximal weakness, muscle pain and fatigue during mild exercise. Laboratory tests showed features of rhabdomyolysis and hypothyroidism. After examination of the thyroid, we reached a diagnosis of Hashimoto's thyroiditis and hypothyroid myopathy. Hypothyroidism should be considered as a differential diagnosis of creatine kinase elevation; actually, neuromuscular symptoms and signs occur in most newly diagnosed patients with thyroid diseases. Hypothyroidism presenting as muscle stiffness and pseudohypertrophy is called 'Hoffman's syndrome'.
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PMID:Hoffman's syndrome: muscle stiffness, pseudohypertrophy and hypothyroidism. 1258 16

Retrospective analysis of immune dysfunctions found in 55 dogs and 62 cats diagnosed with Chronic Fatigue Syndrome (CFS), revealed leukopenia in 11% of dogs (n = 6) and 22.5% of cats (n = 14), lymphopenia in 14.5% of dogs (n = 8) and 10% of cats (n = 6), hypogammaglobulinaemia in 9% of dogs (n = 5) and 13% of cats (n = 8) and thrombocytopenia in 20% of dogs (n = 11) and 68% of cats (n = 42). All patients had creatine kinase enzyme levels above the normal range (CK = 5-100 IU/L) and carried micrococcus-like organisms on erythrocytes. Blood cultures proved positive for Staphylococcus spp. in 16 cases. After low-dosage arsenic-based therapy (thiacetarsamide sodium) all animals experienced complete clinical remission. Subsequent controls demonstrated immune restoration in 4 representative FIV-FeLV negative cats, previously diagnosed with CFS associated with leukopenia, lymphopenia, hypogammaglobulinaemia and thrombocytopenia. The main conclusion is that a CFS-like disease in dogs and cats, characterised by the common hallmarks of high CK levels, absence of known causes of chronic fatigue in animals and presence of micrococcus-like organisms in the blood, can be associated with humoral and/or cellular immune deficiencies in 9-22.5% of cases and with thrombocytopenia in 20-68% of cases. Considerations are made on the possible role of micrococci in the aetiology of the condition and on the similarities with CFS in humans.
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PMID:Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS). 1268 27

A 12-year-old female presented with chronic diarrhea, fatigue, failure to thrive, sudden weakness of her upper and lower extremities and inability to walk. On neurological examination, atrophy was found of the lower extremity muscles, coupled with muscle weakness. Hypokalemia and a high creatine kinase (CK) level were detected. Antigliadin IgA, IgG and antiendomysial antibodies were positive. A duodenal biopsy revealed the classical findings of celiac disease. To our knowledge this is the first childhood case of celiac disease presenting with rhabdomyolysis.
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PMID:Rhabdomyolysis in celiac disease. 1272 76

Skeletal muscle disorders manifested by muscle pain, fatigue, proximal weakness, and serum creatine kinase (CK) elevation have been reported in patients with selenium deficiency. The object of this report was to review the conditions in which selenium deficiency is associated with human skeletal muscle disorders and to evaluate the importance of mitochondrial alterations in these disorders. A systematic literature review using the Medline database and Cochrane Library provided 38 relevant articles. The main conditions associated with selenium deficiency fell into three categories: (1) insufficient selenium intake in low soil-selenium areas; (2) parenteral or enteral nutrition, or malabsorption; and (3) chronic conditions associated with oxidative stress, such as chronic alcohol abuse and human immunodeficiency virus (HIV) infection. In low soil-selenium areas, reversibility of muscle symptoms was similar after selenium supplementation and placebo administration, suggesting a role for other factors in the development of disease. In parenteral or enteral nutrition, or malabsorption, muscle symptoms improved after selenium supplementation in 18 of 19 patients (median delay: 4 weeks). The reason that only a minority of selenium-deficient patients present with skeletal muscle disorders is unclear and is possibly related to cofactors, such as viral infections and drugs. Prospective studies of selenium-deficient myopathies would be useful in critically ill patients, alcohol abusers, and HIV-infected patients.
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PMID:Skeletal muscle disorders associated with selenium deficiency in humans. 1276 76

A 38-year-old man had suffered from general fatigue, mild weakness of proximal muscles, and dry cough in November, 2000. Serum levels of muscle enzymes were elevated. Computed tomography of the chest revealed reticular appearance in the bilateral dorsal lung areas. He did not show any improvement, therefore he was referred to our hospital in April, 2001. He was diagnosed as mild polymyositis with mild interstitial pneumonia. He was treated intravenously with methylprednisolone pulse therapy. During the pulse therapy serum level of creatine kinase was decreased, but he died because of acute pump failure of the heart. The cause of the heart failure could be an exacerbation of chronic myocarditis associated with polymyositis and it was confirmed by autopsy findings. When a patient with mild polymyositis complains of general fatigue, myocarditis should be carefully evaluated because of the high risk of death.
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PMID:[An autopsy case of polymyositis with exacerbation of chronic myocarditis]. 1291 Sep 94


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