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)

Chronic mild dehydration is a common condition in some population groups, including especially the elderly and those who participate in physical activity in warm environments. Hypohydration is recognised as a precipitating factor in a number of acute medical conditions in the elderly, and there may be an association, although not necessarily a causal one, between a low habitual fluid intake and some cancers, cardiovascular disease and diabetes. There is some evidence of impairments of cognitive function at moderate levels of hypohydration, but even short periods of fluid restriction, leading to a loss of body mass of 1-2%, lead to reductions in the subjective perception of alertness and ability to concentrate and to increases in self-reported tiredness and headache. In exercise lasting more than a few minutes, hypohydration clearly impairs performance capacity, but muscle strength appears to be relatively unaffected.
 ...
PMID:Impact of mild dehydration on wellness and on exercise performance. 1468 9

The purpose of this report is to summarize information on oxaliplatin, a drug recently approved by the U.S. Food and Drug Administration. Information provided includes regulatory history, study design, efficacy and safety results, and pertinent literature references. A single, multicenter, randomized trial, enrolling 463 patients with metastatic colorectal carcinoma whose disease had recurred or progressed during or within 6 months of completion of therapy with the combination of bolus 5-fluorouracil (FU)/leucovorin (LV) and irinotecan, was submitted. Study arms included infusional 5-FU/LV alone (arm A), oxaliplatin alone (arm B), and the combination of oxaliplatin and infusional 5-FU/LV(arm C). Oxaliplatin, at a dose of 85 mg/m2, was administered to patients in arms B and C intravenously over 2 hours in 250-500 ml of dextrose 5% in water (D5W) on day 1 only. A 200-mg/m2 dose of LV was administered simultaneously to arm C patients, in a separate bag using a Y-line, or alone to arm A patients, by i.v. infusion, over 2 hours. 5-FU was then administered to arms A and C patients, first as a bolus injection over 2-4 minutes at a dose of 400 mg/m2, then as a continuous infusion in 500 ml of D5W over 22 hours at a dose of 600 mg/m2. LV was repeated on day 2 of the cycle (arms A and C) followed by a 400-mg/m2 5-FU bolus and a 600-mg/m2 22-hour infusion. Treatment was repeated every 2 weeks. Response rate was the prespecified end point for accelerated approval. Time to progression (TTP) was a secondary end point. The prespecified primary comparison was between the 5-FU/LV regimen and the 5-FU/LV/ oxaliplatin combination regimen. The three arms were well balanced for patient prognostic factors. There were no complete responders. The partial response rates were 0%, 1%, and 9% for the 5-FU/LV, oxaliplatin, and oxaliplatin plus 5-FU/LV treatments, respectively (p = 0.0002, arm C versus arm A). The median times to radiographic tumor progression, based on available radiographs, were 2.7 months, 1.6 months, and 4.6 months, respectively (p < 0.0001, arm C versus arm A). Common adverse events associated with the combination treatment included peripheral neuropathy, fatigue, diarrhea, nausea, vomiting, stomatitis, and abdominal pain. Neutropenia was the major hematologic toxicity. Adverse events were similar in men and women and in patients <65 and > or =65 years of age, but older patients may have been more susceptible to dehydration, diarrhea, hypokalemia, and fatigue. Oxaliplatin in combination with infusional 5-FU/LV was approved for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed during or within 6 months of completion of first-line therapy with the combination of bolus 5-FU/LV and irinotecan. Approval was based on response rate and on an interim analysis of TTP. No results are available, at this time, that demonstrate a clinical benefit, such as improvement in disease-related symptoms or survival.
 ...
PMID:FDA drug approval summaries: oxaliplatin. 1475 10

The amounts of water, carbohydrate and salt that athletes are advised to ingest during exercise are based upon their effectiveness in attenuating both fatigue as well as illness due to hyperthermia, dehydration or hyperhydration. When possible, fluid should be ingested at rates that most closely match sweating rate. When that is not possible or practical or sufficiently ergogenic, some athletes might tolerate body water losses amounting to 2% of body weight without significant risk to physical well-being or performance when the environment is cold (e.g. 5-10 degrees C) or temperate (e.g. 21-22 degrees C). However, when exercising in a hot environment ( > 30 degrees C), dehydration by 2% of body weight impairs absolute power production and predisposes individuals to heat injury. Fluid should not be ingested at rates in excess of sweating rate and thus body water and weight should not increase during exercise. Fatigue can be reduced by adding carbohydrate to the fluids consumed so that 30-60 g of rapidly absorbed carbohydrate are ingested throughout each hour of an athletic event. Furthermore, sodium should be included in fluids consumed during exercise lasting longer than 2 h or by individuals during any event that stimulates heavy sodium loss (more than 3-4 g of sodium). Athletes do not benefit by ingesting glycerol, amino acids or alleged precursors of neurotransmitter. Ingestion of other substances during exercise, with the possible exception of caffeine, is discouraged. Athletes will benefit the most by tailoring their individual needs for water, carbohydrate and salt to the specific challenges of their sport, especially considering the environment's impact on sweating and heat stress.
 ...
PMID:Fluid and fuel intake during exercise. 1497 32

A 64-year-old man was admitted to our hospital because of general fatigue and drowsiness. On admission, a physical examination disclosed dehydration and a laboratory investigation revealed the following values: plasma glucose, 1309 mg/dl; serum sodium, 160 mmol/l; potassium, 3.0 mmol/l; urea nitrogen, 65 mg/dl; creatinine, 2.73 mg/dl; and plasma osmolarity, 403 mOsm/kg. Urine ketone bodies were negative. A diagnosis of hyperosmolar non-ketotic diabetic syndrome was made, and hydration with an infusion of hypotonic saline (0.45%) and insulin therapy were immediately started. However, despite adequate rehydration and correction of blood glucose, his serum creatinine level increased to 3.1 mg/dl, while oliguria and myoglobinuria developed on the 4th hospital day, with serum creatine kinase increasing up to a maximum level of 16,749 IU/l, suggesting rhabdomyolysis. A final diagnosis of hyperosmolar non-ketotic diabetic syndrome associated with rhabdomyolysis and acute renal failure was made. His renal function gradually improved without hemodialysis, though acute renal failure due to rhabdomyolysis with hyperosmolar non-ketotic diabetic syndrome can sometimes be fatal. This rare case is presented along with a review of literature.
 ...
PMID:Hyperosmolar non-ketotic diabetic syndrome associated with rhabdomyolysis and acute renal failure: a case report and review of literature. 1500 Apr 44

The development of solutions that prevent dehydration or promote adequate re-hydration play a vital role in preventing fatigue during exercise, however, the methods commonly used to assess the hydration ability of such solutions are invasive and often assess the components of absorption separately. This paper describes using a non-invasive deuterium tracer technique that assesses gastric emptying and intestinal absorption simultaneously to evaluate the uptake of water during rest and exercise. The kinetics of absorption are further examined by mathematical modelling of the data generated. For the rest group, 0.05 g/kg of body weight of deuterium, contained in gelatine capsules, was ingested with ordinary tap water and saliva samples were collected every 5 min for one hour while the subject remained seated. The deuterium was administered as above for the exercise group but sample collection was during one hour of exercise on a treadmill at 55% of the subject's maximum heart rate. The enrichment data for each subject were mathematically modelled and the parameters obtained were compared across groups using an independent samples t-test. Compared with the rest condition, the exercise group showed delayed absorption of water as indicated by significant differences for the modelling parameters t2, t1/2, maximum absorption rate and solution absorption amount at t1. Labelling with a deuterium tracer is a good measure of the relative rate ingested fluids are absorbed by the body. Mathematical modelling of the data generates rates of maximum absorption and allows calculation of the percentage of the solution that is absorbed at any given time during the testing period.
 ...
PMID:Using a non-invasive stable isotope tracer to measure the absorption of water in humans. 1505 81

Numerous studies have confirmed that performance can be impaired when athletes are dehydrated. Endurance athletes should drink beverages containing carbohydrate and electrolyte during and after training or competition. Carbohydrates (sugars) favor consumption and Na(+) favors retention of water. Drinking during competition is desirable compared with fluid ingestion after or before training or competition only. Athletes seldom replace fluids fully due to sweat loss. Proper hydration during training or competition will enhance performance, avoid ensuing thermal stress, maintain plasma volume, delay fatigue, and prevent injuries associated with dehydration and sweat loss. In contrast, hyperhydration or overdrinking before, during, and after endurance events may cause Na(+) depletion and may lead to hyponatremia. It is imperative that endurance athletes replace sweat loss via fluid intake containing about 4% to 8% of carbohydrate solution and electrolytes during training or competition. It is recommended that athletes drink about 500 mL of fluid solution 1 to 2 h before an event and continue to consume cool or cold drinks in regular intervals to replace fluid loss due to sweat. For intense prolonged exercise lasting longer than 1 h, athletes should consume between 30 and 60 g/h and drink between 600 and 1200 mL/h of a solution containing carbohydrate and Na(+) (0.5 to 0.7 g/L of fluid). Maintaining proper hydration before, during, and after training and competition will help reduce fluid loss, maintain performance, lower submaximal exercise heart rate, maintain plasma volume, and reduce heat stress, heat exhaustion, and possibly heat stroke.
 ...
PMID:Fluids and hydration in prolonged endurance performance. 1521 47

Perifosine (NSC 639966) is a synthetic, substituted heterocyclic alkylphosphocholine that acts primarily at the cell membrane targeting signal transduction pathways. Early clinical trials were limited because of dose-limiting gastrointestinal toxicity, and parenteral dosing of this class of agents is not possible because of their hemolytic properties; therefore, related compounds with an improved therapeutic index were developed. Toxicity was minimized and efficacy improved by using a loading dose/maintenance dose schedule, and therefore, this schedule was carried into clinical trials. This phase I trial enrolled 42 patients with incurable solid malignancies. The starting doses were 100 mg p.o. x four doses (every 6 hours) load followed by a 50 mg p.o. once daily maintenance dose with escalation of either component in successive dose levels. No treatment related deaths occurred. The maximum-tolerated dose was determined to be 150 mg p.o. x four doses load and 100 mg p.o. once daily maintenance. Dose-limiting toxicities such as nausea, diarrhea, dehydration, and fatigue were seen early during the loading phase and were surmountable with the use of prophylactic 5-HT3 receptor antagonists, dexamethasone, and loperamide. Toxicities during the chronic phase were difficult to manage and, given that pharmacokinetic data showed biologically active serum concentrations (based on preclinical data), raised the question of less frequent maintenance dosing. Pharmacokinetic data confirmed the maintenance of stable drug levels with chronic dosing and the long half-life. One partial response was seen, as were multiple patients with stable disease beyond course 2. These results suggest perifosine activity in sarcoma and perhaps renal cell carcinoma (stable disease in two patients who continued for 6 and 14 courses), thus justifying additional investigation of this agent in a phase II sarcoma trial.
 ...
PMID:A phase I trial of perifosine (NSC 639966) on a loading dose/maintenance dose schedule in patients with advanced cancer. 1556 74

Competitors in triathlons experience a range of environmental conditions and physiological demands in excess of that found in individual sport events of comparable duration. Consequently, there is a broad range of possible medical problems and complications that must be taken into account when preparing for such races. For most competitors, an Olympic-distance triathlon typically takes between 2-4 hours to complete. This race begins with a swimming segment of 1500 m. Given the wide variety of race venues found around the world, these swims occur in an assortment of water temperatures (from warm to cold) and conditions (from ocean surf to lake calm). Swimmers often exit the water in a state of moderate dehydration and hypothermia and then immediately start the 40 km cycling leg. Many do so in their swimming attire. A wide variety of road surfaces, technically challenging topography, variable environmental conditions and dramatically changing velocities can be encountered on the cycle course. The race concludes with a 10 km running leg. Since it is the final leg, it is often completed in higher ambient temperatures than those encountered at the start, with the athlete possibly running in a significant state of dehydration and fatigue. Other medical problems commonly encountered in triathlon include: muscle cramping, heat illness, postural hypotension, excessive exposure to ultraviolet radiation, musculoskeletal injuries and trauma, gastrointestinal problems as well as post-race bacterial infection, immunosuppression, sympathetic nervous system and psychological exhaustion, and haemolysis. The rate of occurrence of such events and the severity of their potentially negative outcomes is a function of the methods used by both the race organisers and the competitors to prevent or respond to the conditions imposed by the race. Triathletes also commonly compete in both shorter 'sprint distance' events (in the range of a 0.75 km swim, 20 km cycle and 5 km run) and longer events including both one-half and full Ironman distances (2.5 and 3.8 km swim, 80 and 180 km cycle, 20 and 42 km run, respectively), as well as ultra-distance events that exceed the Ironman distance. In the longer events, the previously mentioned medical considerations are further magnified and additional considerations such as hyponatraemia can also occur. Reducing risk associated with these concerns is accomplished by: taking into account weather and water temperature/conditions data prior to event scheduling; effective swim, cycle and run course organisation and management; environmental monitoring prior to and during the event; the implementation of a water safety plan; provision of appropriate fluid replacement throughout the course; implementation of helmet use and non-drafting regulations in the cycling leg; and competitor knowledge regarding fluid replacement, biomechanical technique, physical preparation, safe equipment and course familiarity. Despite these concerns, triathlon participation appears to relatively safe for persons of all ages, assuming that high-risk adults undertake health screening.
 ...
PMID:Medical considerations in triathlon competition: recommendations for triathlon organisers, competitors and coaches. 1570 78

Triathlon combines three disciplines (swimming, cycling and running) and competitions last between 1 hour 50 minutes (Olympic distance) and 14 hours (Ironman distance). Independent of the distance, dehydration and carbohydrate (CHO) depletion are the most likely causes of fatigue in triathlon, whereas gastrointestinal (GI) problems, hyperthermia and hyponatraemia are potentially health threatening, especially in longer events. Although glycogen supercompensation may be beneficial for triathlon performance (even Olympic distance), this does not necessarily have to be achieved by the traditional supercompensation protocol. More recently, studies have revealed ways to increase muscle glycogen concentrations to very high levels with minimal modifications in diet and training. During competition, cycling provides the best opportunity to ingest fluids. The optimum CHO concentration seems to be in the range of 5-8% and triathletes should aim to achieve a CHO intake of 60-70 g/hour. Triathletes should attempt to limit body mass losses to 1% of body mass. In all cases, a drink should contain sodium (30-50 mmol/L) for optimal absorption and prevention of hyponatraemia.Post-exercise rehydration is best achieved by consuming beverages that have a high sodium content (>60 mmol/L) in a volume equivalent to 150% of body mass loss. GI problems occur frequently, especially in long-distance triathlon. Problems seem related to the intake of highly concentrated carbohydrate solutions, or hyperosmotic drinks, and the intake of fibre, fat and protein. Endotoxaemia has been suggested as an explanation for some of the GI problems, but this has not been confirmed by recent research. Although mild endotoxaemia may occur after an Ironman-distance triathlon, this does not seem to be related to the incidence of GI problems. Hyponatraemia has occasionally been reported, especially among slow competitors in triathlons and probably arises due to loss of sodium in sweat coupled with very high intakes (8-10 L) of water or other low-sodium drinks.
 ...
PMID:Nutritional considerations in triathlon. 1570 79

International travel is an essential part of the life of elite athletes, both for competition and training. It is also becoming increasingly common among recreational sportspersons. Long-distance travel is associated with a group of transient negative effects, collectively referred to as 'travel fatigue', which result from anxiety about the journey, the change to an individual's daily routine, and dehydration due to time spent in the dry air of the aircraft cabin. Travel fatigue lasts for only a day or so, but for those who fly across several time zones, there are also the longer-lasting difficulties associated with 'jet lag'. The problems of jet lag can last for over a week if the flight crosses 10 time zones or more, and they can reduce performance and the motivation to train effectively. Knowledge of the properties of the body clock enables the cause of the difficulties to be understood (an unadjusted body clock), and forms the basis of using light in the new time zone to promote adjustment of the body clock. Sleep loss and its effects are important components of jet lag, and attempts to promote sleep by the use of melatonin and other hypnotics are also relevant. Sleep loss is also found in those who undertake challenges that involve long periods where the normal consolidated sleep of 8 h length is not possible. Advice on sleep regimens in such circumstances is given.
 ...
PMID:The stress of travel. 1576 27


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