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)

1. Recruitment order was studied in pairs of motor units of the medial gastrocnemius (MG) muscle of decerebrate cats with the use of dual microelectrode recording from intact ventral root filaments. Excitation was provided by stretch of MG, stretch of synergists [lateral gastrocnemius (LG), plantaris (PL), and soleus (SOL) muscles] or electrical stimulation of the caudal cutaneous sural (CCS) nerve. Motor units were characterized by axonal conduction velocity (CV), tetanic tension (Pmax), twitch contraction time (CT), and fatigue index (FI). 2. Consistent with the recruitment pattern described by others, most often in relation to either CV or Pmax, the first unit of a pair to be recruited by MG stretch was typically the one with the lower CV and Pmax, and the higher FI and CT. The proportion of pairs that agreed in rank order of each property and recruitment order was as follows: for CT, 94%; for CV, 87%; for Pmax, 84%; and for FI, 75%. With a single marginal exception (CT vs. FI), no motor-unit property proved to be significantly better than the others at predicting recruitment (G test; P greater than 0.05). 3. In all 11 tested pairs containing one slow (type S) and one fast (type F) unit, the S was more easily recruited by stretch. Type F units divided into groups with high (type FR), low (type FF), and intermediate (type FInt) values for FI were recruited in order from FR to FInt to FF in 8/11 pairs. Thus our findings were similar to earlier demonstrations that recruitment proceeds in order by type. 4. Stretch of MG synergists usually recruited units in the same order as MG stretch. In two S-S pairs, recruitment order was switched with synergist stretch. 5. Stimulation of the CCS nerve was generally excitatory to the MG units sampled. Most unit pairs were recruited by CCS stimulation in the same order as by MG stretch, but, for 6 of 39 pairs, CCS stimulation switched the order produced by stretch. Thus, whereas sural afferent input can preferentially excite some units over others as suggested by Kanda et al., that effect is not widespread or selective for unit type under these conditions. 6. Assuming that all MG motor units cooperate as a single functional pool in homonymous stretch reflexes, we support others in concluding that a motoneuron's recruitment threshold is not strictly determined by its size. However, our data do not distinguish other schemes that predict recruitment order more accurately than the size principle.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Motor-unit recruitment in the decerebrate cat: several unit properties are equally good predictors of order. 176 76

Due to natural or artificial obstacles, gait is a less automatic and periodic process than it would appear when studying normal walking on the level. Pre-programmed functional electrical stimulation (FES) sequences, therefore, do not appear to be a suitable approach to the control of multichannel electrical stimulators in the restoration of paraplegic walking. Walking in paraplegic subjects must be, to a large extent, under voluntary control. To lessen the burden of this control, the symmetry of walking can be taken into account. Symmetric motion of the legs requires symmetric FES actuation. Symmetry of FES responses was studied in a group of 10 paraplegic subjects who had all undergone the FES training program. Recruitment curve, fatigue index and twitch delay were assessed. An average 80% symmetry was found in all parameters measured, thus allowing a reduction of complexity of control approach for FES locomotor aids.
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PMID:Symmetry of FES responses in the lower extremities of paraplegic patients. 221 30

This study deals with the recruitment characteristics of unfatigued electrically stimulated quadriceps muscles of paraplegic subjects and with the time-dependent force output of these muscles under sustained stimulation conditions. Both these aspects of the performance of paralysed stimulated muscles were studied under isometric conditions and at different muscle lengths. The forces in the knee joint resulting from stimulation of the quadriceps were also calculated. Recruitment force curves due to a ramp-like stimulation function indicated a strong dependence on muscle length and demonstrated a sigmoid-shaped curve with three distinct regions: negligible force up to threshold stimulation intensity; rapid force increase; and levelling-off of the curve after which the force remains constant even though intensity is further increased. When normalized to the maximal force, recruitment was found to be independent of muscle length, generating a typical recruitment curve for every patient, under isometric stimulation. The peak forces were obtained at the same flexion angles previously published for normal subjects, but with much lower values. Muscle fatigue in tetanic isometric conditions, defined as the decrease in force due to sustained stimulation with fixed parameters, was found to be length dependent and to have a double exponential decay. The first is the acute force loss and is the more significant for functional purposes; the second is the more moderate and asymptotic region, in which partial force recovery in the form of bursts is observed.
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PMID:Recruitment, force and fatigue characteristics of quadriceps muscles of paraplegics isometrically activated by surface functional electrical stimulation. 231 65

Average muscle fiber conduction velocity, mean power frequency, and mean EMG voltage have been measured in human vastus lateralis during prolonged isometric knee extensions at 10, 20, 30, and 40% of the maximum knee extension force. During contractions at 10 and 20% of maximum force, conduction velocity and mean power frequency rose as the contraction progressed, whereas the conduction velocity and mean power frequency fell at 30 and 40% of the maximum force. The mean EMG voltage rose during the contractions, with steeper increases for higher forces. It is argued that two principal factors influence the EMG during prolonged submaximal contractions: firstly, the fatigue of current active motor units, and, secondly, recruitment of fresh motor units. These factors act in opposition to muscle fiber conduction velocity. Recruitment gives an increase in average conduction velocity, whereas fatigue provokes a slowing in conduction velocity.
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PMID:Changes in muscle fiber conduction velocity, mean power frequency, and mean EMG voltage during prolonged submaximal contractions. 272 77

A strict interpretation of the size-principle hypothesis (37, 39-41) is that a muscle's motor units should be recruited in an ascending order according to both the size of their motoneurons and the size of their innervated muscle units (for reviews see Refs. 9, 39, 73). Studies of large mixed muscles in the cat hindlimb, however, have shown that motor axonal conduction velocity and tetanic tension, which are frequently considered indices of motoneuron and muscle-unit size, respectively, are uncorrelated in the fast-twitch (type F) motor-unit subpopulation (12, 13, 23, 24, 30, 32, 63, 71, 79). Attempting to focus on type F units, we compared the recruitment order of 42 pairs of cat plantaris (PL) motor units with both axonal conduction velocity and tetanic tension as well as with other muscle-unit properties. Single PL alpha-motor axons were functionally isolated in intact L7 ventral root filaments of decerebrate cats. Tension responses produced by stimulating each isolated motor axon were used to find the tetanic tension of the muscle unit and to classify the unit (12) as either type S (slow twitch, fatigue resistant), type FR (fast twitch, fatigue resistant), type FI (fast twitch, intermediate fatigability), or type FF (fast twitch, highly fatigable). Conduction velocity of each isolated axon was computed from measurements of axonal conduction time and length. The axon's reflex discharges were recorded from the proximal end of the cut filament and compared with the discharges of another PL axon residing in a different, previously cut filament of the same cat. The recruitment order of each motor-unit pair studied was found during reflexes elicited by homonymous muscle stretch, tendon taps, or single shocks at group I intensity to the PL nerve. If either axon of the pair failed to discharge, as often was the case with the high-threshold type F units, the monosynaptic reflex was facilitated by a 500-pps conditioning train applied proximal to a complete reversible cooling block of the PL nerve. In all 42 pairs studied, the weaker motor unit had the lower functional threshold for recruitment. Recruitment also invariably followed the order S greater than FR greater than FI greater than FF units. The motor unit of a pair with the higher resistance to fatigue thus always had the lower functional threshold. In 21 of the 22 pairs containing at least one type S motor unit, the unit with the slower-conducting motor axon had the lower functional threshold for recruitment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relationship among recruitment order, axonal conduction velocity, and muscle-unit properties of type-identified motor units in cat plantaris muscle. 298 33

1. The activity of 40 triceps brachii motor units was recorded from the dominant arms of 9 healthy adult volunteers (age 27.8 +/- 4.4 yr, mean +/- SD) during a fatigue task that included both isometric and anisometric contractions. The fatigue task lasted 8.3 min and consisted of 50 extension and 50 flexion movements of the elbow. Each movement (40 degrees in 0.8s) was separated by an isometric contraction. A constant load resisting extension of 17.7 +/- 3.0% of maximal voluntary contractions (MVC) was applied throughout the task. This paradigm enabled the direct contrast of motor-unit discharge behavior during the different types of fatiguing contractions. 2. Motor-unit behavior was examined to determine the relative contribution of two mechanisms for optimizing force production under fatiguing conditions: recruitment of motor units and modulation of motor-unit discharge following recruitment. Threshold torques for motor-unit recruitment thresholds were determined by ramp-and-hold isometric contractions. Motor-unit discharge was evaluated during the fatigue task by contrasting the number of motor-unit potentials (spikes) per contraction for concentric eccentric, and isometric contractions. 3. The fatigue task resulted in a 30 +/- 12% decline in the mean MVC of elbow extension. Recruitment of nine new motor units (23%) was evident during the fatiguing extension movements, often within five to seven movements (i.e., within 25-35 s). Each newly recruited motor unit had the largest recruitment threshold torque in that experiment. 4. Analysis of the motor units that were active from the beginning of the fatigue task revealed that the mean number of motor-unit spikes per contraction increased, or remained constant as fatigue ensued, yet for the majority of motor units it increased or remained constant. None of the newly recruited motor units demonstrated decreased number of mean spikes per contraction after recruitment. Further, concurrently active motor units displayed different discharge behavior in two-thirds of the subjects. It is proposed that if the neural drive to the muscle is distributed uniformly upon the motoneuron pool, peripheral feedback from the exercising muscle may modulate specific motoneuron discharge levels during fatigue.
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PMID:Motor-unit behavior in humans during fatiguing arm movements. 872 1

1. The recruitment order of 64 pairs of motor units, comprising 21 type-identified units, was studied during centrally evoked muscle contractions of the cat medial gastrocnemius (MG) muscle in an unanesthetized, high decerebrate preparation. Motor units were functionally isolated within the MG nerve by intra-axonal (or intramyelin) penetration with conventional glass microelectrodes. 2. Graded stimulation of the mesencephalic locomotor region (MLR) was used to evoke smoothly graded contractions, which under favorable conditions was estimated to reach 40% of maximum tetanic tension of the MG muscle. With this method of activation, 100% of slow twitch (type S) units, 95% of fast twitch, fatigue-resistant (type FR) units, 86% of fast twitch, fatigue-intermediate (type FI) units, and 49% of fast twitch, fatigable (type FF) units studied were recruited. 3. Motoneuron size as estimated by axonal conduction velocity (CV) was correlated with muscle-unit size as estimated by maximum tetanic tension (Po). Although the correlation between these properties was significant among type S and FR units, no significant correlation was found for these properties among type FI and FF units. 4. Motor-unit recruitment was ordered by physiological type (S > F, 100% of pairs; S > FR > FI > FF, 93% of pairs). Although none of the motor-unit properties studied predicted recruitment order perfectly, motor-unit recruitment was found to proceed by increasing Po (89% of pairs), decreasing contraction time (79% of pairs), decreasing fatigue index (80% of pairs), and increasing CV (76% of pairs). These percentages were significantly different from random (i.e., 50%). Statistically, all four motor-unit properties were equivalent in predicting recruitment order. These results are similar to those reported by other investigators for motor-unit recruitment order evoked from other supraspinal centers, as well as from peripheral sites. 5. When, however, motor-unit recruitment within pairs of motor units containing two fast-twitch (type F) units was examined, Po was a significantly better predictor of recruitment order than CV (85% vs. 52% of pairs). One explanation for this observation is that the correlation between Po and CV is high among type S, type FR units, and possibly among the lower-tension type FF units, but not among the remaining higher-tension type FF units. 6. The reproducibility of recruitment order in multiple contractions was investigated in 16 motor-unit pairs. Recruitment order was found to be variable in only three motor-unit pairs, all of which contained units of similar physiological type and recruitment threshold. 7. Analysis of recruitment order by pair-wise testing confirms the general conclusion reached in human studies that the muscle force level at recruitment for a motor unit is highly correlated with its strength. As an additional confirmation, the whole-muscle force level at recruitment for 41 units was measured in a series of contractions in which the rate of rise of muscle tension was limited to rates < 1,000 g/s. For these contractions, a significant correlation was found between muscle tension at recruitment and motor-unit Po.
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PMID:Activation of type-identified motor units during centrally evoked contractions in the cat medial gastrocnemius muscle. I. Motor-unit recruitment. 882 39

Effective treatment options for high-risk localized prostate cancer are limited. Patients at high risk for recurrence include those with biopsy Gleason scores of 8 to 10, prostate specific antigen (PSA) levels > 20 ng/mL, and clinical stage T3 disease. Docetaxel chemotherapy is active in hormone-refractory prostate cancer, either combined with estramustine or used as a single agent. To determine if systemic therapy can improve the outcome of radical prostatectomy in men with high-risk localized prostate cancer, we are undertaking a pilot phase II clinical trial of weekly docetaxel at 36 mg/m(2) for up to 6 months, followed by surgery. Patients are monitored with weekly visits, monthly digital rectal examinations, PSA measurement, and testosterone tests, and endorectal magnetic resonance imaging done at baseline, after two cycles, and again after six cycles. To date, 15 patients have been enrolled, and 70 cycles of chemotherapy have been administered. Toxicity has been mostly grade 1 in intensity, and fatigue has been the most common grade 2 toxicity reported. The primary endpoint of the trial is measurement of pathologic complete response rate, for which data are not yet available. Recruitment to the trial is ongoing.
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PMID:Neoadjuvant docetaxel followed by radical prostatectomy in patients with high-risk localized prostate cancer: a preliminary report. 1168 27

Vinorelbine (VNR) is a semi-synthetic vinca alkaloid (5'nor-anhydro-vinblastine) that differs from other vinca alkaloids by a modification of the catharantine moiety of the molecule. VNR binds to tubulin and inhibits tubulin assembly and microtubule formation. It has less activity than other vinca alkaloids against axonal microtubules and this may account for its reduced neurotoxicity in clinical use. In gastrointestinal tumours, VNR did not show significant activity in advanced pancreatic adenocarcinomas. Two phase II studies in metastatic colorectal cancer resulted in conflicting results: no activity in first-line therapy on lung metastases, but encouraging results in 5-fluorouracil (5-FU)-resistant metastases. Conversely, significant antitumoural effect in oesophageal squamous cell carcinoma has been demonstrated. The first study was performed in 46 patients with metastatic disease. Six of 30 patients (20%) without prior chemotherapy achieved a partial response (95% confidence interval (CI), 8-39%). One of 16 (6%) with prior chemotherapy responded. Grade (gr) 3 or 4 granulocytopaenia occurred in 59% of patients and peripheral neurotoxicity was minor (26% gr 1). These results were confirmed by another group. A phase I study was performed using VNR and concurrent radiation (64 Gy) in previously untreated patients with inoperable locally advanced oesophageal cancer ineligible for cisplatin-5-FU-based chemoradiation. Twenty-four patients entered the study. The maximal tolerated dose has been reached at 25 mg/m(2)/week, the dose-limiting toxicities being febrile neutropaenia and infection. Major objective tumour response was observed at each dose level except the first one. Recruitment is ongoing to confirm the recommended dose of VNR (20 mg/m(2)/week). A phase II study of a VNR-cisplatin combination in metastatic oesophageal squamous cell carcinoma was recently completed. Seventy-one eligible patients were included. Main toxicities were haematological (gr 3-4 granulocytopaenia, 41%), infection, vomiting and fatigue. The response rate was 37% (95% CI, 26-49%) with a median duration of response of 7.7 months. This 2-day regimen appears at least as active and less toxic than the standard 5-day 5-FU and cisplatin regimen.
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PMID:Activity of vinorelbine in gastrointestinal cancers. 1200 75

BBR3464, a novel tri-nuclear platinum complex, forms long-range DNA adducts and is highly potent when compared with cisplatin in vitro. Preclinical studies demonstrated activity in cisplatin-resistant tumours and tumours with mutated p53 status. Phase I & II clinical studies gave preliminary indications of activity in melanoma, pancreatic, lung and ovarian cancers. The aim of this study was to determine the efficacy and confirm the toxicity of BBR3464 when given either as first- or second-line treatment for advanced disease in patients with gastric and gastro-oesphageal adenocarcinoma. Two multicentre, open label, Gehan design studies were conducted; one study used BBR3464 as first-line and the other as second-line treatment for metastatic or locally advanced disease. Nineteen first-line and 26 second-line patients were enrolled receiving a total of 74 and 53 infusions, respectively. Initially, seven patients in the second-line study received BBR3464 using the planned schedule of 1.1 mg/m2 every 4 weeks; however, 5 of these patients experienced dose-limiting grade 3 or 4 febrile neutropenia; subsequent patients in both studies were treated using the modified schedule of 0.9 mg/m2, every 21 days. In 1 of 17 evaluable, previously untreated patients, regression of multiple skin lesions was noted with stabilisation of lung metastases and maxillary sinus mass, lasting 155 days. In the first-line study, the median time to progression was 85 days [95% Confidence Interval (CI): 42, 127] (2.8 months) and in the second-line study, the median time to progression was 71 days [95% CI: 42, 109] and 38 days [95% CI: 32, 73] in the 1.1 and 0.9 mg/m2 dose level groups, respectively. Toxicity data were available for 45 patients. Neutropenia was the main toxicity seen (G3: 40%, G4: 40%). Febrile neutropenia was observed in six patients (15%) treated with 0.9 mg/m2 compared with five patients (71%) treated with 1.1 mg/m2 BBR3464. Other drug-related toxicities (G3/4) included: anaemia, thrombocytopenia, nausea, vomiting, diarrhoea, mucositis and fatigue. Diarrhoea and nausea/ vomiting were adequately controlled by the use of loperamide and antiemetics, respectively. Recruitment to the second-line study was closed early due to the poor response rate (1/17 evaluable, 6%; 95% CI: 1%, 27%) and short time to progression noted in the first-line study. Further studies with BBR3464 in this tumour type are not recommended.
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PMID:Phase II studies of BBR3464, a novel tri-nuclear platinum complex, in patients with gastric or gastro-oesophageal adenocarcinoma. 1528 89


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