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 estimate the effect of the increase in ventilation induced by exercise on the dynamics of respiratory muscle in normal subjects and cases of respiratory diseases, we measured the changes of transdiaphragmatic pressure (Pdi), gastric pressure (Pga), tension time index of the diaphragm (TTdi) and tension time index of the abdomen (TTab). To confirm the effect of oxygen on exercise endurance, we investigated changes of parameters measured during exercise under air breathing and oxygen inhalation. In normal subjects, we found the increase in diaphragmatic activity as a gradual increase of exercise level, but TTdi always stayed in the non-fatigue zone. On the contrary, patients with COPD showed that TTdi was near fatigue threshold during quiet breathing and crossed easily into fatigue zone during exercise. There was an increase in endurance time with oxygen for COPD patients. Breathing with oxygen was associated with a smooth increase in Pdi during the inspiratory phase which indicates efficient contraction of the diaphragm. During the expiratory phase, the degree of increase in Pga was markedly reduced by oxygen inhalation.
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PMID:[Respiratory muscle fatigue]. 274 68

Ventilatory muscle function was examined at rest and during exercise on a cycle ergometer in 8 patients with moderate to severe chronic air-flow limitation (FEV1, 32 +/- 4% predicted) in air and in oxygen. The diaphragmatic electromyogram (EMG) was measured using an esophageal electrode. In addition, measurements of esophageal (Pes), gastric (Pga), and transdiaphragmatic (Pdi) pressures and abdominal wall movements were made. Patients exercised to exhaustion at a constant submaximal workload (80% of maximal power output) inspiring air or 40% O2 in random order on separate days. At end-exercise in air, tidal inspiratory Pes swings were 36 +/- 4% of static maximal inspiratory Pes, and inspiratory Pdi swings were 45 +/- 7% of the static maximal Pdi. Arterial oxygen saturation decreased from 91 +/- 2% at rest to 80 +/- 5% at end-exercise in air. During exercise in air, 5 patients demonstrated a persistent and greater than 20% fall in the ratio of high frequency (150 to 350 Hz) to low frequency (20 to 46 Hz) power (H/L) of the diaphragmatic EMG, indicating impending diaphragmatic fatigue, and 2 patients had paradoxical motion of the abdominal wall. Exercise time at the same constant work load increased from 3.0 +/- 0.6 min in air to 6.4 +/- 1.2 min in O2 (p less than 0.005). At the comparable time during exercise in O2 to end-exercise in air, minute ventilation was less by 13% (p less than 0.005), which was entirely attributable to a lower frequency of breathing. Mean inspiratory and expiratory flows and heart rate were all significantly lower.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ventilatory muscle function during exercise in air and oxygen in patients with chronic air-flow limitation. 402 48

To determine whether normal ventilatory muscles fatigue during short-term high-intensity exercise, we measured diaphragmatic electromyogram (EMG, esophageal electrode), and pleural (Ppl), gastric (Pga), and transdiaphragmatic (Pdi) pressures in seven normal young men. On separate days, the subjects performed exercise to exhaustion at a constant work load (80% maximum power output) inspiring air or 40% O2. Before and after exercise, Pdimax and maximum expiratory pressure at the mouth (PEmax) were measured. At 0.5-2 min postexercise, there was a decrease in Pdimax in both air (P less than 0.02) and O2 studies (P less than 0.05). There was some recovery in Pdimax from 2-5 min postexercise in air (P less than 0.05) and complete recovery 2-5 min postexercise in O2. PEmax did not change postexercise. During exercise in air, the EMG predicted diaphragmatic fatigue in five subjects using a 20% fall of the ratio of high-frequency (150-350 Hz) to low-frequency) (20-46 Hz) power (H/L) as the criterion. Further evidence of diaphragmatic fatigue during exercise in air in two subjects was the decrease in end-inspiratory Pdi toward end exercise. There was an increase in exercise time with O2 (P less than 0.05). The improved performance in O2 was associated with a delay in the fall in H/L and the absence of the decrease in end-inspiratory Pdi in those subjects in whom such changes were observed in air.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ventilatory muscles during exercise in air and oxygen in normal men. 670 58

Tegafur is an effective oral fluoropyrimidine that shows the same activity as 5-fluorouracil for a similar spectrum of cancers. Their biochemical modulation with oral Leucovorin (LV) attempts to simulate treatment with a continuous infusion of 5-fluorouracil and LV with the added advantage of outpatient administration. Thirty-three patients with advanced adenocarcinoma were included in the study. The treatment consisted of tegafur, 0.75 g/m2/day, for 21 days, with oral LV at different dose levels, 15, 30, 45, 60 and 90 mg/day, in a 28-day cycle. A correlation between the LV dose and an increase in grade III/IV toxicity (especially diarrhea, oral mucositis and fatigue) was established in the nonlinear regression model, reaching a plateau at 60 mg of LV. For the tegafur dose used, the recommended dose of LV is in the range of 45-60 mg/day. This schedule could be considered to evaluate the possible therapeutic effect in phase II trials.
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PMID:Clinical experience with tegafur and low dose oral leucovorin: a dose-finding study. 785 79

The fatigue threshold of the human diaphragm, index of its endurance and fatigability, corresponds, during spontaneous breathing, to a tension-time index (TTdi = Pdi/Pdimax x T1/Ttot (i.e., the inspiratory time over the total breath duration) of 0.15 to 0.18. We studied three quadriplegic patients with diaphragm pacing in order to reassess this threshold in patients in whom the contribution of the other respiratory muscles is lacking. Transdiaphragmatic pressure (Pdi) was obtained from the difference between gastric (Pga) and esophageal (Pes) pressures while the electromyograms (EMG) of both hemidiaphragms were recorded with surface electrodes. Four runs at different TTdi were performed on different days in each subject, varying either the Pdi developed per breath, changing the frequency of stimulation, or the T1/Ttot. The time of fatigue was defined when Pdi decreased during the trials by 35% from baseline. No evidence of transmission fatigue (i.e., decline in action potential amplitude) was observed. The TTdi at which fatigue occurred in all the quadriplegic patients was around 0.10 to 0.12, well below the values previously described. After fatigue had occurred, the force recovery during the force-frequency curve was not complete after 2 h at low frequencies, whereas at high frequencies it was fully complete at 30 min. We conclude that when respiration is accomplished only by the diaphragm, without the contribution of the other respiratory muscles, the fatigue threshold is lower than previously reported.
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PMID:The tension-time index of the diaphragm revisited in quadriplegic patients with diaphragm pacing. 861 61

Leucovorin (LV) enhances the activity of 5-fluorouracil (5FU). Based on these data, we performed a randomized trial with 5FU, epirubicin (EPI), mitomycin C(MMC) with/ without LV in advanced gastric cancer (AGC). The purpose of our study was to investigate if the addition of LV improved the response rate of the combination 5FU EPI, MMC (FEM) over FEM. From January 1988 until April 1994, 88 patients with recurrent or metastatic AGC were randomly received 5FU, EPI, MMC with (group A) or without (group B) LV. Between the two arms of the study no difference was noticed in sex, performance status, primary site of tumor, and lymph node metastases. Therapy included group A (5FU 600 mg/m2/day, i.v. bolus, on days 1, 8, 29, 36, and EPI 45 mg/m2/day, i.v. bolus, on days 1 and 29, MMC 10 mg/m2/day, i.v. bolus, on day 1) and group B (the same as group A plus LV 200 mg/m2/day by 2 h intravenous infusion with 5FU intravenous push at midinfusion). No significant difference in response rate was noticed between the two treatment arms; there were two (5%) patients with complete response in group A, and five (12%) in A and 11 (26%) partial responders in group B (p < 0.1). A significantly higher number of patients achieving stable disease was observed in group B; 19 (44%) in comparison to group A 10 (24%) (p < 0.048). There were more patients with progressive disease in group A 25 (59%) than in group B 12 (28%) (p < 0.003) (Table 2). No difference was noted in mean duration of response: group A, 15.8 (6-31) weeks; and group B, 17.6 (6-28) weeks. The mean time to progression was for group A [11.4 (6-35) weeks] and for group B [17.6 (8-33) weeks]. Mean survival was for group A [27.4 (12-59) weeks] and for group B [30.6 (17-53) weeks], for 50% of patients. Causes of death were, for group A, 40 patients from disease progression and two sudden deaths; for group B, causes of death were for 41 patients disease progression and two sudden deaths. There were two patients in group A and one in group B that were not evaluable because they abandoned therapy after the first cycle. Toxicity was increased in group B; anemia, nausea and vomiting, and alopecia (p < 0.055) were more severe in group B, but not statistically different when compared to group A. Neutropenia, thrombocytopenia, mucositis, and fatigue of any grade were significantly more common and severe in group B. Significant dose reductions due to toxicity were required more commonly in group B. We conclude that the response rate was increased in the schedule with the addition of LV, at the cost of increased toxicity and with no difference in survival. A randomized trial comparing FEM-LV with new generation regimens would determine whether the addition of LV qualifies FAM equally active with these.
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PMID:5-Fluorouracil, epirubicin, and mitomycin C versus 5-fluorouracil, epirubicin, mitomycin C, and leucovorin in advanced gastric carcinoma. A randomized trial. 882 83

The effects of steroid on diaphragmatic contractility and endurance were examined in 24 New Zealand rabbits. Diaphragmatic contractility was determined by measuring gastric pressure (Pga) with the lower thorax and the abdomen of the animal being fixed with a rigid cast. Endurance procedure was done by continuous 15 Hz stimulation of the bilateral phrenic nerves, and diaphragmatic endurance was expressed as the time from the initiation of the endurance procedure to the moment when transdiaphragmatic pressure 15 Hz (Pdi-15 Hz) decreased to 25% of Pdimax-15 Hz. Our data suggested that intravenous administration of dexamethasone 2.5 mg daily for 7 days did not affect the diaphragmatic contractility significantly, but could cause a significant decrease in diaphragmatic endurance. When delivered intravenously at the dose of 2.0 mg daily for 14 days, dexamethasone induced a significant decrease both in diaphragmatic contractility and endurance. The recovery of the diaphragmatic strength from fatigue, however, was not influenced by dexamethasone in either circumstance. The influence of dexamethasone on diaphragmatic contractility and endurance may have important clinical implications.
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PMID:Effects of steroid on diaphragmatic functions in rabbits. 927 6

Inspiratory muscle fatigue can probably determine hypercapnic respiratory failure. Diaphragm fatigue is detected by electrical phrenic stimulation (ELS), but there is no simple tool to assess rib cage muscle (RCM) fatigue. Cervical magnetic stimulation (CMS) costimulates the phrenic nerves and RCM. We reasoned that changes in transdiaphragmatic pressure twitch (Pdi,tw) with CMS and ELS should be different after selective diaphragm vs. RCM fatigue. Five volunteers performed inspiratory resistive tasks while voluntarily uncoupling diaphragm and RCM. Baseline Pdi,twELS and Pdi,twCMS were 28.57 +/- 1.68 and 32.83 +/- 2.92 cmH2O. After selective diaphragm loading, Pdi,twELS and Pdi,twCMS were reduced by 39 and 26%, with comparable decreases in gastric pressure twitch (Pga,tw). Esophageal pressure twitch (Pes,tw) was better preserved with CMS. Therefore Pes,tw/Pga,tw was lower with ELS than CMS (-1.24 +/- 0.16 vs. -1.73 +/- 0.11, P = 0.05). After selective RCM loading, there was no diaphragm fatigue, but Pes,twCMS was significantly reduced (-30%). These findings support the role of rib cage stiffening by CMS-related RCM contraction in the ELS-CMS differences and suggest that CMS can be used to assess RCM fatigue.
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PMID:Cervical magnetic stimulation as a method to discriminate between diaphragm and rib cage muscle fatigue. 957 19

The main objectives of this phase II study were to determine efficacy and safety of the combination of UFT with Leucovorin and mitomycin C in patients with metastatic colorectal cancer. Ninety-seven patients were treated with UFT (91 patients 300 mg/m2, 6 patients 250 mg/m2) + Leucovorin 90 mg days 1-28 q 5 weeks. During the first 4 cycles the patients also received mitomycin C 7 mg/m2 on day 1. At the end of 4 courses patients with benefit from the treatment could receive further courses of UFT and Leucovorin alone. Two patients had a complete response (2%), 20 (21%) had a partial response, 40 (41%) had no change, 19 (20%) had progression, and 16 (17%) were not evaluable for response. The overall response rate by intention to treat was 22/97 (23%). Median time to progression was 5 months and median survival 13 months. Severe (grade 3-4) toxicities included: anorexia 3%, nausea 6%, vomiting 7%, diarrhoea 7%, and fatigue 9%. Febrile neutropenia, renal failure, and thrombocytopenia were seen in 1% of the patients, respectively. The combination of UFT with Leucovorin and mitomycin C shows similar clinical activity with regard to overall response rate (23%) and survival (13 months) to other frontline 5-fluorouracil-based therapies in metastatic colorectal cancer patients. The results indicate that mitomycin C did not increase either efficacy or toxicity. Therefore, phase III trials with this regimen cannot be recommended.
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PMID:A phase II study of UFT and Leucovorin in combination with mitomycin C in patients with metastatic colorectal cancer. 1524 51

The abdominal muscles have been shown to fatigue in response to voluntary isocapnic hyperpnea using direct nerve stimulation techniques. We investigated whether the abdominal muscles fatigue in response to dynamic lower limb exercise using such techniques. Eleven male subjects [peak oxygen uptake (VO2 peak) = 50.0 +/- 1.9 (SE) ml.kg(-1).min(-1)] cycled at >90% VO2 peak to exhaustion (14.2 +/- 4.2 min). Abdominal muscle function was assessed before and up to 30 min after exercise by measuring the changes in gastric pressure (Pga) after the nerve roots supplying the abdominal muscles were magnetically stimulated at 1-25 Hz. Immediately after exercise there was a decrease in Pga at all stimulation frequencies (mean -25 +/- 4%; P < 0.001) that persisted up to 30 min postexercise (-12 +/- 4%; P = 0.001). These reductions were unlikely due to changes in membrane excitability because amplitude, duration, and area of the rectus abdominis M wave were unaffected. Declines in the Pga response to maximal voluntary expiratory efforts occurred after exercise (158 +/- 13 before vs. 145 +/- 10 cmH2O after exercise; P = 0.005). Voluntary activation, assessed using twitch interpolation, did not change (67 +/- 6 before vs. 64 +/- 2% after exercise; P = 0.20), and electromyographic activity of the rectus abdominis and external oblique increased during these volitional maneuvers. These data provide new evidence that the abdominal muscles fatigue after sustained, high-intensity exercise and that the fatigue is primarily due to peripheral mechanisms.
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PMID:Exercise-induced abdominal muscle fatigue in healthy humans. 1642 68


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