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)

Healthy male endurance-trained cyclists [n = 11, age = 27.3 (3.9) years; mass = 73.0 (9.3) kg; height = 180.5 (6.9) cm; maximal oxygen consumption (VO2max) = 71.1 (5.8) ml.kg-1.min-1, mean +/- (SD)] were recruited to assess the relationship between test protocol and the development of desaturation of arterial hemoglobin with oxygen, during incremental exercise tests to maximal aerobic capacity (VO2max). All subjects demonstrated resting pulmonary function within normal limits [forced vital capacity (FVC) = 6.0 (0.9); forced expiratory volume (FEV1.0) = 4.9 (0.6); FEV1.0/FVC = 0.8 (0.1)] and completed three ramped VO2max tests (Mijnhardt KEM-3 electronically braked cycle ergometer) beginning at 0 W with increments of either 20,30 or 40 W.min-1. All periods of testing were separated by a minimum of 72 h. VO2max, peak minute ventilation (VEpeak) (Medical Graphics, CPX-D), peak heart rate (fcpeak), peak power output (Wpeak), and minimum percentage arterial oxyhemoglobin saturation (% SaO2min) (Omeda Biox 3740 pulse oximeter) were determined. There were no significant differences (p > 0.05) in VEpeak [191.5 (26.2), 196.0 (24.4), 194.3 (23.9) l.min-1] fcpeak [191.4 (7.0), 190.3 (5.5), 187.8 (5.9) beats.min-1], VO2max [5.0 (0.5), 5.1 (0.4), 5.1 (0.5) l.min-1] or %SaO2min [89.5 (1.5), 89.6 (1.3), 90.0 (2.3)] between protocols. The 20-W protocol [417 (27) W] demonstrated significantly lower Wpeak (P < 0.05) than the 30-W [434 (36) W] and 40-W [453 (38) W] protocols, indicating that peripheral fatigue may play an important factor in response to these tests. The results of this study demonstrate that arterial desaturation occurs as a result of intense exercise in highly trained athletes independent of the rate of attainment of VO2max.
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PMID:The relationship between test protocol and the development of exercise-induced hypoxemia (EIH) in highly trained athletes. 891 25

This study used a double-dissociation design to evaluate whether children with ADHD demonstrated specific deficits relative to children with Reading Disorders. Recent theory suggests that ADHD children have deficits in time perception and working memory, whereas RD children have deficits in phonological decoding. The performance of 113 clinic-referred children aged 6-11 was examined using measures of working memory, phonological processing, and time perception. Respondents completed two time production tasks in which they were to judge when 30-s had elapsed, and another in which they were asked to estimate the duration of the Conners' CPT (CCPT). Time Perception and phonological processing variables were submitted to a 2 x 2 ANCOVA (ADHD vs. RD), covarying for age, SES, IQ, and working memory. Children with ADHD were more likely to overestimate the time taken for the CCPT than children without ADHD, but no group differences were found on the 30-s estimation tasks. Children with RD did not display deficits in time estimation, but showed deficits in auditory phonological processing. The lack of interaction effects supported an "etiological subtype" over the "phenocopy" model of ADHD and RD. No group differences were detected using the CCPT. Although our previous studies did not find an order effect for the Conners' CPT in a 1-hr battery, a fatigue effect was evident with a 1.5-hr battery. The implications for Barkley's behavioral inhibition theories (R. Barkley, 1997) are discussed.
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PMID:Time perception: does it distinguish ADHD and RD children in a clinical sample? 1550 28

Smoking is highly prevalent among patients with Attention Deficit Hyperactivity Disorder (ADHD). Previous studies using the reversed continuous performance task (R-CPT) have suggested that nicotine reduces inattention. Since especially adults with ADHD have been claimed to suffer from a core deficit in inhibitory control, this study aimed at determining whether nicotine improves response inhibition in addition to attention. Sixteen healthy regular smokers participated in a pre/post treatment design in which transdermal patches containing 7 and 21 mg nicotine per day were administered in a counterbalanced, double-blind manner. In a second study, patches containing 0 mg (placebo) and 21 mg per day were administered to a different group of regular smokers. For replication purposes, the R-CPT and the profile of mood states (POMS) were administered. Furthermore, a different version of the continuous performance task (CPT-AX) and the stop-signal task, traditionally used to measure response inhibition, were presented. The high dose of nicotine was found to relieve self-reported Depression in Study 1 and Fatigue in Study 2. Performance data indicated acute effects of nicotine on attention-related, but not on inhibition-related measures. Especially the comparison with placebo revealed decreases in reaction time and variability of responding. The results imply that patients with ADHD smoke to reduce inattention.
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PMID:Acute effects of nicotine on attention and response inhibition. 1636 Aug 13

We investigated habituation effects during thermal quantitative sensory testing (tQST) using 8 repetitive measurements for thermal detection and pain thresholds. The same measurements were repeated two days later. 39 healthy subjects and 36 patients with chronic non-neuropathic pain syndromes (migraine, tension-type headache, non-radicular back pain) were enrolled. The pain intensity was assessed using an 11-point (0-10) numerical rating scale. Measurements correlated significantly over the two days in both groups (r=0.41...0.62). Warm detection (WDT) and heat pain threshold (HPT) revealed no significant differences over these days. Cold detection (CDT) and pain thresholds (CPT) showed significant differences but these were small compared to the range of normal variability (CDTDelta -0.28 degrees C; CPTDelta 1.51 degrees C). On both days, WDT showed no habituation during measurements. Although there was a small difference in CDT and CPT between first and second measurement, there was no habituation beyond the second stimuli. In contrast, HPT significantly increased between first and sixth stimuli, indicating pronounced habituation. Average HPT of first to third measurement was significantly lower than HPT of the fourth to sixth assessment (45.9 degrees C; 47.7 degrees C) with a good day-to-day repeatability. Repeatability and habituation was identical in both groups. Ongoing pain intensity in the patient groups correlated significantly with CDT/WDT but not with CPT, HPT, indicating that ongoing pain might suppress the sensitivity to non-painful stimuli. In summary, tQST proved a reliable diagnostic tool for clinical practice. Day-to-day differences were small but without clinical relevance. Habituation was most pronounced for HPT, probably due to peripheral fatigue of the receptors.
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PMID:Habituation and short-term repeatability of thermal testing in healthy human subjects and patients with chronic non-neuropathic pain. 1901 13

We report a case of stem fracture of a collarless, polished, double-taper cemented stainless steel femoral prosthesis. Scanning electron microscopy showed fatigue striations, indicating failure by fatigue. This case study highlights that stem fracture can still occur with modern implants. Size 0 CPT stem should be avoided in patients with high body mass index. To our knowledge this is the first case report of a CPT stem fracture used for primary total hip replacement.
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PMID:Stem fracture of a collarless, polished, double-taper cemented femoral prosthesis: a case report. 1905 9

A 61-year-old man admitted to our hospital for diarrhea and general fatigue was found in endoscopic and radiological examination to have sigmoid colon cancer with multiple liver metastases. The patient underwent sigmoidectomy (S, type 2, 105x78 mm, sSI (urinary bladder), sN0 (0/22), sH3 (Grade C), sP0, sM0, sStage IV). Pathological report was following: tub2, pSI (urinary bladder), ly0, v1, pN0(0/22), PM0, DM0, RM0. After operation, the patient received systemic chemotherapy (CPT-11+UFT/LV) with hepatic arterial infusion therapy(HAI). We could not observe any severe adverse events. We conducted hepatectomy because of partial response by chemotherapy. As of this writing 41 months after surgery, the patient continues to do well with no signs of recurrence. The combination chemotherapy of CPT-11+UFT/LV with HAI was safe and effective treatment for the patients with unresectable liver metastases from colorectal cancer.
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PMID:[A case report of multiple liver metastases from colorectal cancer effectively treated with systemic chemotherapy and hepatic arterial infusion]. 2003 62

Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. Previous work showed that adenosine A(2A) antagonists can reverse the effects of DA D(2) antagonists on effort-related choice. However, less is known about the effects of adenosine A(1) antagonists. Despite anatomical data showing that A(1) and D(1) receptors are co-localized on the same striatal neurons, it is uncertain if A(1) antagonists can reverse the effects DA D(1) antagonists. The present work systematically compared the ability of adenosine A(1) and A(2A) receptor antagonists to reverse the effects of DA D(1) and D(2) antagonists on a concurrent lever pressing/feeding choice task. With this procedure, rats can choose between responding on a fixed ratio 5 lever-pressing schedule for a highly preferred food (i.e. high carbohydrate pellets) vs. approaching and consuming a less preferred rodent chow. The D(1) antagonist ecopipam (0.2 mg/kg i.p.) and the D(2) antagonist eticlopride (0.08 mg/kg i.p.) altered choice behavior, reducing lever pressing and increasing lab chow intake. Co-administration of the adenosine A(1) receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.375, 0.75, and 1.5 mg/kg i.p.), and 8-cyclopentyltheophylline (CPT; 3.0, 6.0, 12.0 mg/kg i.p.) failed to reverse the effects of either the D(1) or D(2) antagonist. In contrast, the adenosine A(2A) antagonist KW-6002 (0.125, 0.25 and 0.5 mg/kg i.p.) was able to produce a robust reversal of the effects of eticlopride, as well as a mild partial reversal of the effects of ecopipam. Adenosine A(2A) and DA D(2) receptors interact to regulate effort-related choice behavior, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing, fatigue or anergia that can be observed in depression and other disorders.
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PMID:Differential effects of selective adenosine antagonists on the effort-related impairments induced by dopamine D1 and D2 antagonism. 2060 Jun 75

Patients with advanced solid malignancies were enrolled to an open-label, single-arm, dose-escalation study, in which CRLX101 was administered intravenously over 60 min among two dosing schedules, initially weekly at 6, 12, and 18 mg/m(2) and later bi-weekly at 12, 15, and 18 mg/m(2). The maximum tolerated dose (MTD) was determined at 15 mg/m(2) bi-weekly, and an expansion phase 2a study was completed. Patient samples were obtained for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Response was evaluated per RECIST criteria v1.0 every 8 weeks. Sixty-two patients (31 male; median age 63 years, range 39-79) received treatment. Bi-weekly dosing was generally well tolerated with myelosuppression being the dose-limiting toxicity. Among all phase 1/2a patients receiving the MTD (n = 44), most common grade 3/4 adverse events were neutropenia and fatigue. Evidence of systemic plasma exposure to both the polymer-conjugated and unconjugated CPT was observed in all treated patients. Mean elimination unconjugated CPT Tmax values ranged from 17.7 to 24.5 h, and maximum plasma concentrations and areas under the curve were generally proportional to dose for both polymer-conjugated and unconjugated CPT. Best overall response was stable disease in 28 patients (64 %) treated at the MTD and 16 (73 %) of a subset of NSCLC patients. Median progression-free survival (PFS) for patients treated at the MTD was 3.7 months and for the subset of NSCLC patients was 4.4 months. These combined phase 1/2a data demonstrate encouraging safety, pharmacokinetic, and efficacy results. Multinational phase 2 clinical development of CRLX101 across multiple tumor types is ongoing.
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PMID:First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies. 2339 98

A modeling framework relating exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor (sVEGFR)-2, -3, soluble stem cell factor receptor (sKIT)), and tumor growth to overall survival (OS) was extended to include adverse effects (myelosuppression, hypertension, fatigue, and hand-foot syndrome (HFS)). Longitudinal pharmacokinetic-pharmacodynamic models of sunitinib were developed based on data from 303 patients with gastrointestinal stromal tumor. Myelosuppression was characterized by a semiphysiological model and hypertension with an indirect response model. Proportional odds models with a first-order Markov model described the incidence and severity of fatigue and HFS. Relative change in sVEGFR-3 was the most effective predictor of the occurrence and severity of myelosuppression, fatigue, and HFS. Hypertension was correlated best with sunitinib exposure. Baseline tumor size, time courses of neutropenia, and relative increase of diastolic blood pressure were identified as predictors of OS. The framework has potential to be used for early monitoring of adverse effects and clinical response, thereby facilitating dose individualization to maximize OS.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e85; doi:10.1038/psp.2013.62; advance online publication 4 December 2013.
CPT Pharmacometrics Syst Pharmacol 2013 Dec 04
PMID:PKPD Modeling of Predictors for Adverse Effects and Overall Survival in Sunitinib-Treated Patients With GIST. 2430 78

We conducted a phase II study of combination chemotherapy with paclitaxel (Pac) and irinotecan (CPT) to determine the effects and toxicities in patients 70 years or older with unresectable non-small cell lung cancer (NSCLC). Eligible patients were entered to receive three courses of Pac at 160 mg/m2 and CPT at 60 mg/m2 every 2-3 weeks. Twenty-one patients were registered. Thirteen patients were male and 8 were female, with a median age of 72 years (range: 70-82 years). Eight patients had a performance status (PS) of 0 and the other 13 patients had a PS of 1. Six and 15 patients were stage IIIB and stage IV, respectively. Ten patients received 3 to 6 cycles of the chemotherapy. Of the hematological toxicities, grade 4 neutropenia was observed in 23.8% of the patients. Of the non-hematological toxicities, grade 3 or 4 fatigue, anorexia and nausea were observed in 5, 3 and 4 patients, respectively. Three of 6 patients with infection developed grade 3 pneumonia. Grade 3 allergy with rash occurred in a patient. Cerebral infarction occurred in two patients and grade 3 peripheral neuropathy in one. The outcome of the Pac and CPT regimen in 21 patients was 8 PR, 10 SD and three PD, and the response rate was 38.1% The median survival time was 9.1 months. The one- and 2-year survival rates were 38.1% and 19.0%, respectively. The Pac plus CPT regimen is feasible and active with moderate toxicity for elderly patients with NSCLC.
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PMID:Prospective study of paclitaxel and irinotecan for elderly patients with unresectable non-small cell lung cancer. 2441 95


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