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)

Aromatase inhibitors and inactivators are playing an increasing greater role in breast cancer treatment. Exemestane, a highly specific, steroidal aromatase inactivator, is the newest agent in this class. The drug is highly specific, and inhibits the in vivo conversion of androstenedione to oestrone (aromatization) by a mean of 97.9%. Exemestane has shown good efficacy and tolerability in multiple clinical trials among patients with metastatic breast cancer who have failed one or more previous hormonal therapies. Exemestane 25 mg/day slows disease progression and reduces tumour-related signs and symptoms and the drug exhibits a partial lack of cross-resistance with the non-steroidal aromatase inhibitors. Response rates to exemestane of 14% to 29% were observed including patients with visceral metastases, who have historically proven difficult to treat. In a large phase III trial, exemestane was found to be superior to megestrol acetate with respect to time to progression and overall survival. In addition, exemestane is currently under investigation as first-line therapy in metastatic disease and in sequence with tamoxifen in the adjuvant setting. Adverse events include low-grade hot flashes, nausea, and fatigue--mostly of mild to moderate intensity--and treatment-related discontinuations are rare. In conclusion, exemestane represents a novel and interesting drug for the treatment of advanced breast cancer, with exciting prospects for use in adjuvant therapy and, potentially, breast cancer prevention.
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PMID:Exemestane: a review of its clinical efficacy and safety. 1496 85

Vinegar is generally believed to be good for health. A mash consisting of 35% ethanolic extract from bitter melon malt vinegar-water (8:50:42) was subjected to further acetate fermentation and the resulting vinegar was converted to dried vinegar powder by spray drying after adsorption on dextrin, which was mixed with a commercial rat chow (CRF-1) in the ratio of 1:19 so as to prepare an experimental diet. Male 12-wk old rats of LETO and OLETF strains were fed this experimental diet in parallel with CRF-1 (control) and examined for respiratory quotient (RQ) and blood or plasma parameters associated with diabetes mellitus. Administration of the experimental diet increased daily food intake as well as daily energy expenditure in both strains. RQ significantly lessened in the vinegar diet-fed group of LETO strain, which was reflected not only in the increased energy consumption from fat but also in the decreased energy consumption from carbohydrate, while no significant difference was observed between both dietary groups of OLETF strain in this respect. The profiles of diurnal energy expenditure in both dietary groups of LETO strain exerted two peaks before lights-on and lights-off. Nevertheless, there was a clear difference between both dietary groups of OLETF strain: interestingly the reproduction of the two peaks became conspicuous in the vinegar diet-fed group despite the lack of such peaks in the control. As a consequence of blood or plasma inspection, it turned out that there was no change in HbA1c but a significant increase in plasma cholesterol in the vinegar diet-fed OLETF rats. From these results, a long-term administration of bitter melon malt vinegar can be expected to suppress a lowering of energy turnover inherent with aging and thereby improve anorexia rather than to bring about a preventive effect against the manifestation of NIDDM.
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PMID:Bitter melon malt vinegar increases daily energy turnover in rats. 1497 34

With the increasing indications for the use of androgen-deprivation therapy in the treatment of men with prostate cancer, side effects of the therapy deserve greater attention. Side effects such as hot flashes, decreased libido, decreased sexual function, and fatigue primarily affect the patients quality of life. Other side effects such as osteoporosis and changes in lipid profiles may also affect the patients overall health. Treatments such as estrogen, megestrol acetate, antidepressants, and bisphosphonates are useful in the management of many of the deleterious side effects of androgen deprivation. In addition, alternative management strategies such as intermittent androgen ablation and antiandrogen monotherapy may be useful in minimizing side effects caused by androgen ablation. Patients and physicians should be well aware of the potential side effects of androgen-deprivation therapy as well as the preventive and treatment strategies for these side effects in order to improve patients quality of life and health.
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PMID:Complications of androgen-deprivation therapy for prostate cancer. 1504 Aug 57

Management of the patient with multiple sclerosis (MS) encompasses a number of distinct, if overlapping, areas. They include anticipation and prevention of problems, symptom control, drug therapies aimed at reducing disease activity and finally, rehabilitation and service delivery. The recent advent of new immunosuppressant treatments for MS is extremely exciting. Beta-interferons (1a and 1b) are now licensed worldwide and glatiramer acetate (Copaxane) is in use in the United States. Many more drugs, including intravenous immunoglobulin, mitoxantrone, methotrexate and cladribine, are undergoing trials and some are showing promising results. Future therapies with monoclonal antibodies and adhesion molecules are also undergoing extensive research. Realistically, however, these new treatments aimed at reducing disease activity will have little impact on existing problems or the degree of disability. Consequently, much of the management of a patient with MS relates to control of the vast array of symptoms. These range from the obvious problems of weakness and spasticity, ataxia and sphincter disturbance, to less common but still important problems such as visual, cognitive, swallowing and respiratory difficulties. Some of the most common, and to the patient most disabling, symptoms are fatigue, thermal sensitivity and pain, areas often neglected by the physician in the face of more obvious physical needs. Much can be done for the patient in all areas. A combination of education, physiotherapy and drug therapy is usually required but occasionally there is a place for more invasive treatments such as intrathecal baclofen administration for severe spasticity or thalamic surgery for cerebellar tremor. A multidisciplinary team approach is essential in the overall management of the patient with MS, particularly when assessing their needs as a basis for both inpatient rehabilitation programs and in the provision of a comprehensive community-based service.
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PMID:The management of multiple sclerosis: current and future therapies. 1509 56

Previous studies have shown the possibility of developing in-situ polymerizable hydrogels that disclose a range of properties that might allow for their use as bone cements. Their main advantage is to be partially degradable, which is important to allow bone ingrowth (better fixation). In addition, their uptake of water makes them less agressive for the tissues, disclosing better fatigue properties and ideal for release of drugs when in service. This work reports a statistical study of the formulation of partially degradable acrylic bone cements that include on their composition corn starch/cellulose acetate blends (SCA). The aim was to optimize a set of properties (mechanical, swelling/degradation and curing) by changing the values of some parameters such as SCA amount and particle size and molar ratio of the acrylic monomers. Statistical tests demonstrated that the most important parameter was the molar ratio of monomers, with the SCA percentage also playing a role. It was possible to develop formulations with mechanical properties in the range of ASTM specifications and with polymerization temperatures lower than those of commercial acrylic cements. Some formulations were subsequently selected for tensile and dynamic mechanical thermal analysis (DMA) tests, under dry and wet conditions.
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PMID:Optimization of the formulation and mechanical properties of starch based partially degradable bone cements. 1533 94

Multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system (CNS), 2 results in damage to axons and their surrounding myelin sheath. The exact cause of inflammation remains unclear, but an autoimmune response directed against CNS antigens is suspected. MS can affect the brain, optic nerve and spinal cord, thus causing many neurological symptoms. These can include limb numbness or weakness, sensory or motor changes, ataxia, blurry vision, painful eye movements, bladder and bowel dysfunction, decreased memory, fatigue and effective disorders. This article will include a concise overview of the pathogenesis of MS in order to set the stage for subsequent discussion of the mechanisms of action of disease-modifying treatments, and whether these should influence our treatment choices. Although the exact pathogenesis of MS is not fully understood, current knowledge has already led to the development of effective treatments, namely interferon (IFN) 3 and glatiramer acetate, both of which have been shown to reduce relapse rates, while IFN 3- 1 a also reduces confirmed disability progression. Further increases in our understanding of the pathogenesis of MS are likely to assist in the identification of new targets for disease-modifying therapies and in the optimisation of current treatments..
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PMID:What do we know about the mechanism of action of disease-modifying treatments in MS? 1554 50

Although addition of an antioxidant (alpha-tocopherol) is reported to prevent delamination in ultrahigh molecular weight polyethylene (UHMWPE) knee components, contribution of alpha-tocopherol as an antioxidant to the improvement of long-term fatigue performance of UHMWPE is an unknown mechanism. To solve this problem, bi-directional sliding fatigue tests were performed for gamma-irradiated (25 kGy), gamma-irradiated (25 kGy) with 0.3 wt% alpha-tocopherol added, and gamma-irradiated (25 kGy) with 0.3 wt% tocopheryl acetate added UHMWPE specimens. Internal defect initiation was quantified with scanning acoustic tomography (SAT). Also, oxidation index and crystallinity were obtained from infrared absorption spectra measured using Fourier transform infrared (FT-IR) microscopy. Only gamma-irradiated UHMWPE specimens resulted in severe fatigue fractures. alpha-Tocopherol-added UHMWPE specimens showed significantly lower projected area ratio of defects (1.80+/-0.82) than did gamma-irradiated (7.0+/-2.29) and tocopheryl acetate-added ones (8.50+/-2.01). The oxidation index of gamma-irradiated UHMWPE specimens (0.111+/-0.0052) was extremely higher compared to those of doped ones; 0.0179+/-0.0026 and 0.0144+/-0.0069 for alpha-tocopherol-added and tocopheryl acetate-added ones, respectively. The crystallinity of gamma-irradiated UHMWPE specimens (57.5+/-1.16) was lower compared to those of doped ones; 60.3+/-0.72 and 60.4+/-1.38 for alpha-tocopherol-added and tocopheryl acetate-added ones, respectively. The incorporation of alpha-tocopherol significantly improves the long-term fatigue performance of gamma-irradiated UHMWPE with oxidation stability. Also, the addition of alpha-tocopherol controls macromolecular structures resulting in the improvement of fatigue performance of UHMWPE.
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PMID:The anti-oxidative properties of alpha-tocopherol in gamma-irradiated UHMWPE with respect to fatigue and oxidation resistance. 1594 42

The objective of the study was to assess factors associated with treatment satisfaction among patients receiving antihypertensive therapy. A weighted cross-sectional online survey was conducted with hypertensive patients participating in a chronic disease panel in the US. Patients on monotherapy with medications from the following classes were identified: ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta blockers (BBs), calcium channel blockers (CCBs), and diuretics. The control group included patients without treatment. Pairwise comparisons between groups were conducted for factors that may affect patients' satisfaction. The study population had a mean age of 54.7+/-14.2 years and was 56.7% female. Participants with blood pressure (BP) controlled to JNC 7 guidelines were more satisfied with their medication than those with uncontrolled BP (90.3 vs 71.5%, P<0.05). Patients who had not experienced adverse events had higher satisfaction than patients experiencing adverse events (90.9 vs 75.8%, P<0.05). The most frequently self-reported adverse events were frequent urination, sexual dysfunction, and fatigue ranging from 7.0 to 9.6% across classes. The adverse event rates differed by class and were lowest among the ARBs. Patients on ARBs were the most likely to have switched from a previous antihypertensive class as compared to other classes (57.1% ARBs vs 49.8% ACEIs, 38.7% diuretics, 36.3% CCBs, and 31.7% BBs). Physician recommendation was the most common reason for switching. In conclusion, the ability to effectively treat hypertension depends upon a patient's satisfaction with antihypertensive therapy, which may be improved by achieving BP control and minimizing the occurrence of adverse events.
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PMID:Patient satisfaction with antihypertensive therapy. 1595 40

The first pyrethroid pesticide, allethrin, was identified in 1949. Allethrin and other pyrethroids with a basic cyclopropane carboxylic ester structure are type I pyrethroids. The insecticidal activity of these synthetic pyrethroids was enhanced further by the addition of a cyano group to give alpha-cyano (type II) pyrethroids, such as cypermethrin. The finding of insecticidal activity in a group of phenylacetic 3-phenoxybenzyl esters, which lacked the cyclopropane ring but contained the alpha-cyano group (and hence were type II pyrethroids) led to the development of fenvalerate and related compounds. All pyrethroids can exist as at least four stereoisomers, each with different biological activities. They are marketed as racemic mixtures or as single isomers. In commercial formulations, the activity of pyrethroids is usually enhanced by the addition of a synergist such as piperonyl butoxide, which inhibits metabolic degradation of the active ingredient. Pyrethroids are used widely as insecticides both in the home and commercially, and in medicine for the topical treatment of scabies and headlice. In tropical countries mosquito nets are commonly soaked in solutions of deltamethrin as part of antimalarial strategies. Pyrethroids are some 2250 times more toxic to insects than mammals because insects have increased sodium channel sensitivity, smaller body size and lower body temperature. In addition, mammals are protected by poor dermal absorption and rapid metabolism to non-toxic metabolites. The mechanisms by which pyrethroids alone are toxic are complex and become more complicated when they are co-formulated with either piperonyl butoxide or an organophosphorus insecticide, or both, as these compounds inhibit pyrethroid metabolism. The main effects of pyrethroids are on sodium and chloride channels. Pyrethroids modify the gating characteristics of voltage-sensitive sodium channels to delay their closure. A protracted sodium influx (referred to as a sodium 'tail current') ensues which, if it is sufficiently large and/or long, lowers the action potential threshold and causes repetitive firing; this may be the mechanism causing paraesthesiae. At high pyrethroid concentrations, the sodium tail current may be sufficiently great to prevent further action potential generation and 'conduction block' ensues. Only low pyrethroid concentrations are necessary to modify sensory neurone function. Type II pyrethroids also decrease chloride currents through voltage-dependent chloride channels and this action probably contributes the most to the features of poisoning with type II pyrethroids. At relatively high concentrations, pyrethroids can also act on GABA-gated chloride channels, which may be responsible for the seizures seen with severe type II poisoning. Despite their extensive world-wide use, there are relatively few reports of human pyrethroid poisoning. Less than ten deaths have been reported from ingestion or following occupational exposure. Occupationally, the main route of pyrethroid absorption is through the skin. Inhalation is much less important but increases when pyrethroids are used in confined spaces. The main adverse effect of dermal exposure is paraesthesiae, presumably due to hyperactivity of cutaneous sensory nerve fibres. The face is affected most commonly and the paraesthesiae are exacerbated by sensory stimulation such as heat, sunlight, scratching, sweating or the application of water. Pyrethroid ingestion gives rise within minutes to a sore throat, nausea, vomiting and abdominal pain. There may be mouth ulceration, increased secretions and/or dysphagia. Systemic effects occur 4-48 hours after exposure. Dizziness, headache and fatigue are common, and palpitations, chest tightness and blurred vision less frequent. Coma and convulsions are the principal life-threatening features. Most patients recover within 6 days, although there were seven fatalities among 573 cases in one series and one among 48 cases in another. Management is supportive. As paraesthesiae usually resolve in 12-24 hours, specific treatment is not generally required, although topical application of dl-alpha tocopherol acetate (vitamin E) may reduce their severity.
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PMID:Poisoning due to pyrethroids. 1618 Sep 29

Phorbol esters activate protein kinase C and modulate a variety of downstream cell signaling pathways. 12-O-tetradecanoylphorbol-13-acetate (TPA) is a phorbol ester that induces differentiation or apoptosis in a variety of cell lines at low concentrations. A phase I dose escalation trial of TPA was undertaken for patients with relapsed or refractory malignancies. The starting dose was 0.063 mg/m2 and most patients were treated with an intravenous infusion of TPA on days 1-5 and 8-12 followed by a 2-week rest period prior to retreatment. Thirty-five patients were treated. A biological assay was used to monitor levels of TPA-like activity in the blood after treatment. Serious adverse events included individual episodes of gross hematuria, a grand mal seizure, syncope, and hypotension. Many patients had transient fatigue, mild dyspnea, fever, rigors, and muscular aches shortly after the infusion. Dose-limiting toxicities included syncope and hypotension at a dose of 0.188 mg/m2. Only a single patient had evidence of tumor response. These studies establish 0.125 mg/m2 as the maximally tolerated dose when TPA is administered on this schedule.
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PMID:A phase I clinical trial of 12- O-tetradecanoylphorbol-13-acetate for patients with relapsed/refractory malignancies. 1623 Nov 82


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