Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ventilatory pump failure can occur in the setting of severe infection. Recent in vivo studies have shown a significant decrease in diaphragm force production in rats with pneumococcal sepsis and sepsis secondary to Escherichia coli endotoxin. We hypothesized that diaphragm impairment during sepsis may be mediated by a direct effect of tumor necrosis factor-alpha (TNF) or endotoxin. To test this hypothesis we studied the mechanical characteristics of isolated rat diaphragm strips in tissue baths containing rTNF-alpha or endotoxin and compared the results with control strips. The strips were stimulated to contract isometrically in the tissue baths that were aerated with 95% O2-5% CO2. Baseline force-frequency determinations were made at 60 min. Following this, the strips were fatigued over a 4-min period (20 Hz, 0.33-s trains, 1 train/s) and force-frequency relationships determined 30 s, 10 min, and 60 min post-fatigue. There were no significant differences found between control and experimental strips in any aspect of contractile function tested, including force-frequency characteristics, fatiguability, and recovery from fatigue. Using an isolated cell line assay (L929), we found evidence of attenuated cytotoxicity of TNF at 26 degrees C compared with 37 degrees C. Therefore, we repeated the experiments studying the effects of TNF on in vitro muscle at 37 degrees C. We once again found no effect of TNF on contractile function. We conclude that the impairment of diaphragm function during sepsis is not mediated by a direct effect of TNF or endotoxin.
 ...
PMID:Tumor necrosis factor and endotoxin do not directly affect in vitro diaphragm function. 834 89

A 68-year-old man with severe dyspnea was admitted as an emergency case. He had no past history of any respiratory or neuromuscular diseases. Immediately after insufflation of oxygen, respiratory arrest occurred. The blood gas analysis showed hypoxemia and severe hypercapnia (PaO2; 32 mmHg, PaCO2; 127 mmHg). We diagnosed as CO2 narcosis, and he was treated with a respirator in the ICU. He showed nonflaccid bilateral diaphragmatic paralysis and muscle atrophy of the upper extremities. As the EMG showed giant spikes of neurogenic pattern, he was diagnosed as ALS. Weaning from the respirator failed because of his respiratory muscle fatigue. He was given rehabilitation during the day time and ventilatory support with the respirator during the night. We conclude that if we meet with an emergency patient with CO2 narcosis without any pulmonary disorder, we have to suspect neuromuscular diseases, e.q. ALS. In some of such cases, mechanical ventilation supports social rehabilitation.
 ...
PMID:[A case of emergency admission for CO2 narcosis in a patient with amyotrophic lateral sclerosis]. 852 59

Patients with chronic heart failure have an increased ventilation/carbon dioxide production ratio (VE/VCO2) during exercise. Recently it was discussed whether the cause of this increase was a ventilatory stimulus driven other than by CO2. Dyspnoea during exercise is thought to be related to impaired respiratory function. However, clinical confirmation is scarce. Ninety-two patients (age 51 +/- 9 years) with heart failure due to idiopathic dilated cardiomyopathy exercised on a bicycle ergometer to exhaustion, and measurement of ventilatory gases and Swan-Ganz catheterization were performed. The maximal oxygen consumption corrected for body weight (VO2max. kg-1) was 16.6 +/- 5.5 ml x min-1 x kg-1. The increase in (VE/VCO2) during exercise was related to an increase in respiratory rate (r = 0.43; P < 0.00001) but not to an increase in cardiac index or capillary wedge pressure. Nineteen patients stopped exercising because of dyspnoea. Their maximal tidal volume and VO2max . kg-1 were lower than the 67 patients who stopped exercise because of fatigue (P < 0.001 and P < 0.00001 respectively). Other variables showed no significant difference. In conclusion, the increase in VE/VCO2 during exercise may reflect a non-CO2 driven ventilatory stimulus as it cannot be attributed to increased pulmonary vascular pressures or an insufficient increase in cardiac output leading to a ventilation-perfusion mismatch. Low oxygen uptake is a prominent finding in patients with chronic heart failure who experienced dyspnoea during exercise, and dyspnoea is in part related to impaired respiratory function.
 ...
PMID:Ventilation and dyspnoea during exercise in patients with heart failure. 868 22

1. The aim of this study was to investigate the analgesic effect and its duration of a new sustained-release preparation of tramadol in an experimental pain model based on pain-related chemosomatosensory evoked potentials (CSSEPs) and subjective intensity estimates of painful phasic and tonic stimuli. 2. Twenty volunteers participated in a randomised, double-blind, three-fold cross-over study. Measurements were obtained before and 0.5, 1, 4, 6, and 12 h after administration of the drug (100 mg, 200 mg and placebo orally). CSSEPs were recorded after stimulation of one nostril with phasic, painful CO2 pulses. The other nostril was stimulated with a constant stream of dry air, which produced a tonic painful sensation. Subjects rated the perceived intensity of phasic and tonic stimuli via visual analogue scales. In order to test for nonspecific effects, acoustic evoked potentials (AEPs) were recorded, the spontaneous EEG was analysed in the frequency domain, the subject's vigilance was assessed in a tracking task, and the side effects of the drug were monitored. 3. The sustained-release preparation of tramadol produced a significant dose-related decrease in CSSEP amplitudes when compared with placebo. The reduction in amplitudes outlasted the observation period of 12 h, demonstrating the prolonged duration of the analgesic effect. 4. A dose-related significant decrease could be observed for the estimates of tonic pain. Similar to the decrease of amplitudes of the CSSEP, the reduction of the ratings of tonic pain outlasted the observation period of 12 h. The observed slight decrease in the estimates of phasic pain under medication did not reach a statistically significant level when compared with placebo. No significant effect could be demonstrated for the perception of the phasic and the tonic pain as determined by the McGill-Questionnaire. 5. A significant dose-related increase in the estimates of the side effects 'drowsiness', 'vertigo' and 'sickness' but not for 'tiredness' could be demonstrated.
 ...
PMID:Dose dependent time course of the analgesic effect of a sustained-release preparation of tramadol on experimental phasic and tonic pain. 883 37

The cellular mechanism of muscle fatigue is still in debate. Opposite conclusions regarding the role of intracellular pH (pHi) in fatigue have been drawn from skinned fiber vs. isolated perfused muscle studies. Because these experiments are typically performed at different temperatures, we tested the hypothesis that temperature alters the effects of pH on force. Tetanic force of isolated mouse extensor digitorum longus was measured at temperatures between 13 and 25 degrees C in either normocapnia (5% CO2) or hypercapnia (25% CO2). Hypercapnia decreased pHi (monitored by 31P nuclear magnetic resonance spectroscopy) by the same amount at both 15 and 25 degrees C. However, inhibition of force by hypercapnia was greater at the lower temperature. A similar pattern of temperature-dependent inhibition of force by pH was observed in glycerinated fibers from rabbit psoas at maximum Ca2+ activation. We conclude that temperature differences are responsible for disparate conclusions on the role of pHi in muscle fatigue. Based on our results, we suggest that changes in pHi may have little or no role in the loss in force production associated with muscular fatigue at physiological temperatures.
 ...
PMID:Effect of intracellular pH on force development depends on temperature in intact skeletal muscle from mouse. 884 18

Prospective registry of newly diagnosed cases of insulin-dependent diabetes mellitus in subjects under 20 years began in 1988 in Aquitaine, Lorraine, Basse- and Haute-Normandie (population base = 2,288,018 inhabitants under 20). The registry gave a complete coverage of the population as the capture-recapture method gave a 98% yield. The mean annual incidence was 7.6/100,000 for the period 1988-1990. A specific survey aimed at describing clinical and biological presentation at diagnosis. The main symptom was polyuria in 98% of the cases, fatigue in 58% and weight loss in 44%. Abdominal pain was reported in 34% of the cases. Diagnosis was ascertained by measurement of plasma glucose, which was > or = 11 mmol/l in 95% of the cases and associated with ketonuria in 84% of the children. Coma in 13% of the children and acidosis (total CO2 < or = 18 mmol/l) in 48% showed the severity at diagnosis. Ketonuria and acidosis were significantly more frequent in the younger age group (0-4 yr). Diagnosis was made by a general practitioner in the majority of the cases; conversely insulinotherapy was initiated at the hospital in 95% of the cases. Initial insulin treatment was 2 daily injections. Following the French experience the collaborative network EURODIAB ACE has undertaken the same survey among the European Registries. Important geographical variations in incidence rates of IDDM in children has been reported across Europe but it is not known whether this interferes with presentation at diagnosis of the disease.
 ...
PMID:[Diagnosis of insulin-dependent diabetes in children: data from the incidence registry]. 893 70

We used bilateral phrenic nerve stimulation (BPNS; at 1, 10, and 20 Hz at functional residual capacity) to compare the amount of exercise-induced diaphragm fatigue between two groups of healthy subjects, a high-fit group [maximal O2 consumption (VO2max) = 69.0 +/- 1.8 ml.kg-1.min-1, n = 11] and a fit group (VO2max = 50.4 +/- 1.7 ml.kg-1.min-1, n = 13). Both groups exercised at 88-92% VO2max for about the same duration (15.2 +/- 1.7 and 17.9 +/- 2.6 min for high-fit and fit subjects, respectively, P > 0.05). The supramaximal BPNS test showed a significant reduction (P < 0.01) in the BPNS transdiaphragmatic pressure (Pdi) immediately after exercise of -23.1 +/- 3.1% for the high-fit group and -23.1 +/- 3.8% (P > 0.05) for the fit group. Recovery of the BPNS Pdi took 60 min in both groups. The high-fit group exercised at a higher absolute workload, which resulted in a higher CO2 production (+26%), a greater ventilatory demand (+16%) throughout the exercise, and an increased diaphragm force output (+28%) over the initial 60% of the exercise period. Thereafter, diaphragm force output declined, despite a rising minute ventilation, and it was not different between most of the high-fit and fit subjects. In summary, the high-fit subjects showed diaphragm fatigue as a result of heavy endurance exercise but were also partially protected from excessive fatigue, despite high ventilatory requirements, because their hyperventilatory response to endurance exercise was reduced, their diaphragm was utilized less in providing the total ventilatory response, and possibly their diaphragm aerobic capacity was greater.
 ...
PMID:Aerobic fitness effects on exercise-induced low-frequency diaphragm fatigue. 894 41

Impaired pulmonary gas exchange can result from lung parenchymal failure inducing oxygenation deficiency and fatigue of the respiratory muscles, which is characterized by hypercapnia or a combination of both mechanisms. Contractility of and coordination between the diaphragm and the thoracoabdominal respiratory muscles predominantly determine the efficiency of spontaneous breathing. Sepsis, cardiac failure, malnutrition or acute changes of the load conditions may induce fatigue of the respiratory muscles. Augmentation of spontaneous breathing is not only achieved by the application of different technical principles or devices; it also has to improve perfusion, metabolism, load conditions and contractility of the respiratory muscles. Intermittent mandatory ventilation (IMV) allows spontaneous breathing of the patient and augments alveolar ventilation by periodically applying positive airway pressure tidal volumes, which are generated by the respirator. Potential advantages include lower mean airway pressure (PAW), as compared with controlled mechanical ventilation, and improved haemodynamics. Suboptimal IMV systems may impose increased work and oxygen cost of breathing, fatigue of the respiratory muscles and CO2 retention. During pressure support ventilation (PSV), inspiratory alterations of PAW or gas flow (trigger) are detected by the respirator, which delivers a gas flow to maintain PAW at a fixed value (usually 5-20 cm H2O) during inspiration. PSV may be combined with other modalities of respiratory therapy such as IMV or CPAP. Claimed advantages of PSV include decreased effort of breathing, reduced systemic and respiratory muscle consumption of oxygen, prophylaxis of diaphragmatic fatigue and an improved extubation rate after prolonged periods of mechanical ventilation. Minimum alveolar ventilation is not guaranteed during PSV; thus, close observation of the patient is mandatory to avoid serious respiratory complications. Continuous positive airway pressure breathing (CPAP) maintains PAW above atmospheric pressure throughout the respiratory cycle, which may increase functional residual capacity and decrease the effort of breathing. CPAP has been conceptually designed for the augmentation of spontaneous breathing and requires the intact central and peripheral regulation of the respiratory system. Airway pressure release ventilation (APRV) improves alveolar ventilation by intermittent release of PAW, which is kept above atmospheric pressure by means of a high-flow CPAP system. The opening of an expiratory valve for 1-2 s induces a decreased PAW and lung volume, which increases rapidly to pre-exhalation values after closure of the valve due to the high gas flow within the circuit (90-100 1/min). APRV may improve haemodynamics and VA/Q distribution as compared with conventional mechanical ventilation. Biphasic positive airway pressure (BIPAP) is characterized by the combination of spontaneous breathing and time-regulated, pressure-controlled mechanical ventilation. During the respiratory cycle the ventilator generates two alternating CPAP levels, which can be modified with regard to time and pressure. As with APRV, alveolar ventilation is maintained even if the spontaneous breathing efforts of the patient cease, which improves the safety of both modes of respiratory therapy. The contribution of spontaneous breathing to total minute ventilation may be important, since a decreased shunt and improved VA/Q relationship have been observed in experimental non-cardiogenic lung oedema. These data give support to the concept that spontaneous breathing should be maintained and augmented in the setting of acute respiratory failure.
 ...
PMID:[Augmented spontaneous breathing]. 896 3

In this double-blind placebo controlled study the preoperative cardiovascular and metabolic effects of intramuscular (i.m.) clonidine and midazolam are assessed. Forty-five ASA Grade I patients (n = 15 per group) undergoing plastic surgical procedures were randomly allocated to receive either placebo, clonidine 4 micrograms kg-1 or midazolam 70 micrograms kg-1. Drugs were administered into the deltoid muscle approximately 90 min prior to the scheduled induction of anaesthesia. The metabolic measurements were performed using an indirect calorimetry device. Heart rate and blood pressure were measured noninvasively. Pre-operative subjective anxiety, dryness of mouth and tiredness were assessed using visual analogue scales (VAS). Clonidine increased subjective tiredness significantly more than placebo. Clonidine also induced moderate decreases in blood pressure and heart rate. Oxygen consumption (VO2), CO2 production and energy expenditure (EE) decreased significantly after clonidine and midazolam. The decrease in VO2 and EE was maximally 11-14% on average from the base-lines after clonidine and midazolam. These effects were of longer duration after clonidine and lasted until the end of the 90 min study period. In conclusion, both clonidine and midazolam are effective as a means of decreasing pre-operative VO2 and EE.
 ...
PMID:Cardiovascular and metabolic responses to clonidine and midazolam premedication. 908 19

1. The effect of altered intracellular pH (pHi) on isometric contractions and shortening velocity at 12, 22 and 32 degrees C was studied in intact, single fibres of mouse skeletal muscle. Changes in pHi were obtained by exposing fibres to solutions with different CO2 concentrations. 2. Under control conditions (5% CO2), pHi (measured with carboxy SNARF-1) was about 0.3 pH units more alkaline than neutral water at each temperature. An acidification of about 0.5 pH units was produced by 30% CO2 and an alkalinization of similar size by 0% CO2. 3. In acidified fibres tetanic force was reduced by 28% at 12 degrees C but only by 10% at 32 degrees C. The force increase with alkalinization showed a similar reduction with increasing temperature. Acidification caused a marked slowing of relaxation and this slowing became less with increasing temperature. 4. Acidification reduced the maximum shortening velocity (V0) by almost 20% at 12 degrees C, but had no significant effect at 32 degrees C. Alkalinization had no significant effect on V0 at any temperature. 5. In conclusion, the effect of pHi on contraction of mammalian muscle declines markedly with increasing temperature. Thus, the direct inhibition of force production by acidification is not a major factor in muscle fatigue at physiological temperatures.
 ...
PMID:The effect of intracellular pH on contractile function of intact, single fibres of mouse muscle declines with increasing temperature. 909 43


<< Previous 1 2 3 4 5 6 7 8 9 10