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)

To evaluate the frequency of the causes of exercise limitation in patients with chronic pulmonary disease and to assess the relationship between the resting pulmonary functional parameters and the degree of exercise dyspnea, we reviewed the data from 88 consecutive stable patients with chronic lung disease (62 COPD, 16 interstitial lung disease [ILD]). In each patient, the intensity of dyspnea was measured by a Borg scale (BS) during an incremental symptom-limited exercise test. COPD patients stopped exercise due to fatigue (46%), dyspnea (36%), cardiac limitation (12%), and peripheral circulatory limitation (6%). ILD patients stopped exercise due to dyspnea (62%), fatigue (25%), and cardiac limitation (12%). In all patients, dyspnea severity increased linearly with exercise intensity as measured as VO2, VE, and VE/MVV. The severity of dyspnea expressed as the slope of the relationship between BS and VE/MVV (DBS/D[VE/MVV]) showed in COPD a significant inverse correlation with VC, FEV1, MIP, and a positive correlation with PaCO2 and VE/MVV at rest. In ILD, DBS/D(VE/MVV) showed a significant inverse correlation with VC, FEV1, TLC, and PaO2 and a positive correlation with VE/MVV at rest. The predicting power of all equations was very low.
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PMID:Dyspnea on exercise. Pathophysiologic mechanisms. 157 44

The reduced respiratory muscle strength and increased work of breathing in patients with severe chronic obstructive pulmonary disease (COPD) may predispose these patients to the development of respiratory muscle fatigue and consequent respiratory failure. To test the hypothesis that these patients may be experiencing chronic respiratory muscle fatigue, we studied the effects of resting the respiratory muscles in a group of patients with severe COPD. Fifteen stable patients with severe COPD were randomized into study and control groups. In 8 study group patients (Group B), breathing was assisted with a negative pressure ventilator 3 to 6 h daily for 3 consecutive days. The remaining 7 patients served as controls (Group A) and did not receive any intervention. Baseline lung function was evaluated by spirometry and arterial blood gas determinations. Respiratory muscle strength and endurance were evaluated by maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and the maximal duration that isocapnic hyperventilation equal to 50 and 70% of the 12-s maximal voluntary ventilation could be sustained (DSV). Baseline DSV was determined as the best effort of several practice trials. All measurements were repeated on the final day of assisted ventilation approximately 2 to 3 h after its discontinuation. After assisted ventilation, the DSV at 50 and 70% of the maximal voluntary ventilation improved significantly (p less than 0.05). Maximal inspiratory pressure and MEP increased to 114% (p less than 0.05) and 112% (p = 0.05) of baseline values, respectively. Mean arterial PCO2 in the hypercapnic subgroup of Group B patients decreased from 60 mm Hg before to 52 mm Hg after assisted ventilation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intermittent negative pressure ventilation on respiratory muscle function in patients with severe chronic obstructive pulmonary disease. 310 44

Patients with congestive heart failure (CHF) suffer from respiratory muscle weakness which may contribute to dyspnea. Nasal continuous positive airway pressure (NCPAP) can improve left ventricular ejection fraction (LVEF) and reduce dyspnea in patients with CHF and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) but its effects on respiratory muscle strength are not known. We therefore studied the effects of NCPAP on maximal inspiratory and expiratory pressures (MIP and MEP, respectively), LVEF, dyspnea, and fatigue in patients with chronic CHF and CSR-CSA over 3 mo. Eight patients were randomized to control and nine to nightly NCPAP. There were no significant changes in any of these factors in the control group during the study. In contrast, among the NCPAP group, MIP increased from 79.3 +/- 8.1 to 90.7 +/- 10.4 cm H2O (mean +/- SEM; p < 0.02), LVEF increased from 24.0 +/- 4.0 to 32.6 +/- 6.6% (p < 0.02) and symptoms of dyspnea and fatigue were alleviated. However, MEP did not change. In addition, the number of apneas and hypopneas decreased from 49 +/- 11 to 17 +/- 7 per hour of sleep (p < 0.001) and mean low Sao2 during sleep increased from 87.9 +/- 1.0 to 93.0 +/- 1.0% (p < 0.01). Our data indicate that nightly application of NCPAP in patients with CHF and CSR-CSA improves inspiratory muscle strength and LVEF, and relieves dyspnea and fatigue.
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PMID:CPAP improves inspiratory muscle strength in patients with heart failure and central sleep apnea. 854 29

Lung transplantation recipients have reduced exercise capacity despite normal resting pulmonary and hemodynamic function. The limiting factor may be contractile dysfunction of skeletal muscle. To test this postulate, we measured limb and respiratory muscle function in nine clinically stable lung allograft recipients (six men and three women, aged 30 to 65 yr, at 5 to 102 mo after transplantation) with reduced exercise capacity. Respiratory muscle strength was tested by measuring maximal inspiratory and expiratory pressure (MIP and MEP, respectively). Ankle dorsiflexor muscle strength was measured during maximal voluntary contraction (MVC). In a subset of six recipients, we also measured contractile properties and fatigue characteristics of the tibialis anterior muscle, using electrical stimulation of the motor point. Data were compared with values from age- and sex-matched control subjects. MIP values of transplant recipients did not differ from control values; however, MEP was blunted by 30% relative to control (p < 0.05), and MVC was decreased by 39% (p < 0.05). The force-frequency relationships and fatigue characteristics of the tibialis anterior were not different between the patient and control groups. We conclude that stable lung allograft recipients experience expiratory and lower limb weakness that may contribute to exercise intolerance.
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PMID:Respiratory and limb muscle function in lung allograft recipients. 1050 8

Ankylosing spondylitis (AS) has been shown to produce exercise limitation and breathlessness. The purpose of this study was to investigate factors which may be responsible for limiting aerobic capacity in patients with AS. Twenty patients with no other cardio-respiratory disease performed integrative cardiopulmonary exercise testing (CPET). The results were compared to 20 age and gender matched healthy controls. Variables that might influence exercise tolerance, including pulmonary function tests (body plethysmography), respiratory muscle strength (MIP, MEP) and endurance (Tlim), AS severity assessment including chest expansion (CE), thoracolumber movement (TL), wall tragus distance and peripheral muscle strength assessed by maximum voluntary contraction of the knee extensors (Qds), hand grip strength and lean body mass (LBM), were measured in the patients with AS and used as explanatory variables against the peak VO2 achieved during CPET. As subjects achieved a lower peak VO2 than controls (25.2 +/- 1.4 vs. 33.1 +/- 1.6 ml kg-1min-1, mean +/- SEM, P = 0.001). When compared with controls, ventilatory response (VE/VCO2) in AS was elevated (P = 0.01); however gas exchange indices, transcutaneous blood gases and breathing reserve were similar to controls. AS subjects developed a higher HR/VO2 response (P < 0.01) on exertion but without associated abnormalities in ECG, blood pressure response or anaerobic threshold. The AS group experienced a greater degree of leg fatigue (P < 0.01) than controls at peak exercise. Although the breathlessness scores (BS) were comparable to controls at peak exercise, the slopes of the relationship between BS and work rate (WR) [AS 0.054 (0.1), Controls 0.043 (0.06); P < 0.05] and BS and % predicted oxygen uptake [AS 0.084 (0.18), Controls 0.045 (0.06); P < 0.01] were steeper in the AS subjects. There was weak association between peak VO2 and vital capacity (r2% 12.0), MIP (11.8) but no association between Tlim, CE, Wall tragus distance or TL movement. The strongest association with aerobic capacity was between measurements of peripheral muscle strength (Qds; r = 0.75; hand grip; r = 0.47) accounting for 53% (P < 0.001) and 23.5% (P < 0.01) of the total variance in peak VO2, respectively. The addition of LBM to Qds in the regression model significantly improved the explained variance to 78.3% (P < 0.001). This study shows that peripheral muscle function is the most important determinant of exercise intolerance in AS patients suggesting that deconditioning is the main factor in the production of the reduced aerobic capacity.
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PMID:An investigation of factors limiting aerobic capacity in patients with ankylosing spondylitis. 1058 58

One of the mechanisms proposed to explain the decrement in pulmonary function often seen after exercise is fatigue of the expiratory muscles. To test the hypothesis that expiratory muscle fatigue alters lung function, several indices of pulmonary function were measured before and after expiratory muscle fatigue was induced by expiratory loaded breathing. Eight subjects completed a fatigue trial (EF) in which expiratory threshold loaded breathing was performed at an initial resistance equal to 80 % of their maximal expiratory pressure (MEP), at a respiratory rate of 13 bpm, and a duty cycle (T(I)/T(Tot)) of 0.33. MEP was taken at predefined intervals throughout the loaded breathing protocol, and loaded breathing was discontinued when MEP was less than 80 % of each subject's pre EF trial MEP (T(Lim)). FVC, FEV(1.0), FEF(25 %), FEF(25-75 %), and maximal inspiratory and expiratory pressures (MIP and MEP) were taken prior to, immediately after, and at 5, 10, and 15 min post fatigue. On a separate day a control trial (CON) was performed that was identical to each subjects EF trial with the exception that no expiratory load was utilized. At T(Lim) MEP was significantly reduced (p < 0.001) by 23.5 % from the pre-expiratory loaded breathing value (183.1 +/- 39.56 to 140.13 +/- 30.45 mmHg), whereas it remained unchanged during the CON trial (191.06 +/- 44.18 to 188.06 +/- 43.50 mmHg). FVC measured prior to and immediately after T(Lim) remained unchanged following both the EF (5349.45 +/- 1130.8 to 5387.43 +/- 1139.92 mL) and CON trials (5287.75 +/- 1220.29 and 5352.78 +/- 1191.30 mL). These results suggest that any expiratory muscle fatigue developed during exercise by itself does not result in altered pulmonary function. However, any interactions between expiratory muscle fatigue and other consequences of exercise that may alter lung function cannot be ruled out.
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PMID:Pulmonary function subsequent to expiratory muscle fatigue in healthy humans. 1159 Apr 76

The function of respiratory muscles, and mainly inspiratory muscles, is impaired in COPD patients. Most of these impairments are essentially due to pulmonary hyperinflation that puts these muscles in a disadvantageous situation. The main consequence of this dysfunction is respiratory muscle fatigue that may cause shortness of breath, exertion intolerance, and hypoventilation with onset of hypercapnic respiratory failure. This function may be measured at the pulmonary function laboratory by means of unspecific (spirometry, pulmonary volumes) or specific tests (maxim respiratory pressures [MIP - M], transdiaphragmatic pressure, tension-time index of the diaphragm, electromyography, or endura tests). Therapy should aim at improving hyperinflation with bronchodilator therapy, improving muscular strength with rehabilitation, and in severe cases muscle rest with mechanical ventilation. Peripheral muscle dysfunction is a common complication in moderate-severe COPD, and it may be the result of chronic inactivity, hypoxemia, electrolytic impairments, under nutrition, steroids, oxidative stress, and systemic inflammation. Besides, it may contribute to patients' quality of life worsening, disability, and even an increase in morbimortality. It may tested by impedanciometry, muscle strength tests (dynamometry), imaging tests, and even muscle biopsy in research studies. Peripheral muscle dysfunction is potentially manageable with rehabilitation, nutritional supplementation, and anabolic drugs. However, therapeutic success is often incomplete, so that further studies with new therapeutic strategies are needed.
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PMID:[Clinical consequences of muscle dysfunction in chronic obstructive pulmonary disease]. 1676 33

The effects of training on dynamic hyperinflation in stable chronic obstructive pulmonary disease (COPD) were investigated by using a controlled study of 28 subjects with FEV(1) = 42.5 (8.3 SD)%pred and 20 matched controls [FEV(1) = 44.9 (10.4)%pred]. Training consisted of spending 45 min/day, 4 days/week on a cycle-ergometer for six weeks. Maximal inspiratory and expiratory pressures (MIP and MEP), lung volumes, and two constant-work-rate (CWR) exercise tests (low- and high-intensity) were performed. Significant (p < 0.0l) improvements in the training group were observed in MIP [+8 (12) cmH(2)O], MEP [+18 (20) cmH(2)O], and endurance to high-intensity CWR [+7(5) min], and there were significant decreases in respiratory rate and end-expiratory lung volume (EELV) during both exercise tests. At 5 min, EELV decreased 0.1(0.08) L and 0.31(0.13) L and at end of exercise, EELV decreased by 0.09(0.07) L and 0.15(0.11) L respectively, for the moderate- and high-intensity tests. Dyspnea also decreased significantly at both exercise intensities. No changes were observed in the control group. Increased endurance showed independent significant (p < 0.05) correlation with changes in EELV, leg fatigue, and MEP. EELV changes showed a significant negative correlation with resting inspiratory capacity. We conclude that exercise training has beneficial effects on respiratory pattern and dynamic hyperinflation that may partially explain the reduction in dyspnea and the improvement in exercise tolerance.
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PMID:A controlled trial of the effects of leg training on breathing pattern and dynamic hyperinflation in severe COPD. 1690 41

Although many factors that trigger the herpes simplex virus (HSV) reactivation from latency have been reported, how HSV resides in a latent state in the normal human cornea still needs to be defined. We therefore conducted a series of studies regarding various aspects of HSV infections. To understand how patients subjectively perceived changes in their daily life that could have induced HSV reactivation, we first performed a comprehensive survey on the subjective factors in patients who had experienced recurrent herpetic keratitis. The result of our survey revealed that stress, lack of sleep, shoulder stiffness, and physical fatigue were the key factors. There were various causes for stress, and stress associated with reactivation often occurred between spring and summer. Regarding HSV latency in the normal cornea, we used real-time polymerase chain reaction (PCR) to determine the presence of HSV in the donor and host corneas. The findings showed that on average, those host corneas with a history of HSV keratitis had 1.6 x 10(4) copies/mg of HSV DNA, while the host corneas without a history and the donor corneas had 8.7 and 4.9 x 10(2) copies/mg of HSV DNA, respectively. Based on these observations, it is reasonable to infer that latent viruses could have resided in a normal cornea without a history and were transmitted to a host cornea through corneal transplantation. We also quantified the virus load in tears before and after ocular surgery (one week after corneal transplantation or the next day after vitreous surgery). Our results indicated that both the detection rate and the average copy number of HSV DNA had a tendency to increase postperatively. Moreover, we tried to differentiate the HSV strains that were involved in the recurrent lesions. In only one of the studied cases, could we find a single different nucleotide between two HSV strains. It seemed possible that two different strains of HSV had set off the same episode of reactivation. In recent years, chemokines have become known for their action in mediating inflammatory diseases. We suspected that chemokines might also play a role in the antiviral mechanism and examined the chemokine-derived antiviral activity. We used eight chemokines, including RANTES/CCL5, MIP-lalpha/ CCL3, and MIP-1beta/CCL4, in a murine HSK model with Vero cells. These chemokines directly bound to HSV and the chemokine-bound HSV was later resisted by the neutralizing antibody of envelope protein gB. Furthermore, by electron microscope analysis, it became clear that these chemokines had cut an opening in the HSV envelope. Consequently, these chemokines had significantly inhibited the HSV infection on Vero cells. In addition, the virus load in tears was decreased and the corneal opacity was less severe. We concluded in that study that during early infection, chemokines accumulated in the corneal stroma have the ability to protect cells and tissues from HSV infection. As for antiviral therapy, acyclovir (ACV) eye ointment has been effective for patients with herpetic keratitis. However, patients often find it difficult to successfully follow the treatment due to the required frequent application and the blurred vision after application. On the other hand, valaciclovir (VCV), which is the oral prodrug of ACV, has become commercially available in recent years for treating nonocular herpetic diseases. We therefore examined and compared the efficacies of oral VCV, oral ACV, ACV eye ointment, and ACV eye drops in a murine keratitis model; the group treated with oral VCV did show a significantly good antiviral effect. We have proved that oral VCV can be a beneficial alternative antiviral therapy for patients with difficulty in complying with the ACV eye ointment treatment.
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PMID:[Herpes simplex virus latency, reactivation, and a new antiviral therapy for herpetic keratitis]. 1841 13

The intracellular Ca(2+) concentration ([Ca(2+)](i)) in skeletal muscles must be rapidly regulated during the excitation-contraction-relaxation process. However, the signalling components involved in such rapid Ca(2+) movement are not fully understood. Here we report that mice deficient in the newly identified PtdInsP (phosphatidylinositol phosphate) phosphatase MIP/MTMR14 (muscle-specific inositol phosphatase) show muscle weakness and fatigue. Muscles isolated from MIP/MTMR14(-/-) mice produced less contractile force, had markedly prolonged relaxation and showed exacerbated fatigue relative to normal muscles. Further analyses revealed that MIP/MTMR14 deficiency resulted in spontaneous Ca(2+) leakage from the internal store - the sarcoplasmic reticulum. This was attributed to decreased metabolism (dephosphorylation) and the subsequent accumulation of MIP/MTMR14 substrates, especially PtdIns(3,5)P(2) and PtdIns (3,4)P(2). Furthermore, we found that PtdIns(3,5)P(2) and PtdIns(3,4)P(2) bound to, and directly activated, the Ca(2+) release channel (ryanodine receptor 1, RyR1) of the sarcoplasmic reticulum. These studies provide the first evidence that finely controlled PtdInsP levels in muscle cells are essential for maintaining Ca(2+) homeostasis and muscle performance.
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PMID:Deficiency of MIP/MTMR14 phosphatase induces a muscle disorder by disrupting Ca(2+) homeostasis. 1946 20


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