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)

Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalization and mortality. However, it is becoming recognized that frailty may be a distinct clinical syndrome with a biological basis. The frailty process appears to be a transitional state in the dynamic progression from robustness to functional decline. During this process, total physiological reserves decrease and become less likely to be sufficient for the maintenance and repair of the ageing body. Central to the clinical concept of frailty is that no single altered system alone defines it, but that multiple systems are involved. Clinical consensus regarding the phenotype which constitutes frailty, drawing upon the opinions of numerous authors, shows the characteristics to include wasting (loss of both muscle mass and strength and weight loss), loss of endurance, decreased balance and mobility, slowed performance, relative inactivity and, potentially, decreased cognitive function. Frailty is a distinct entity easily recognized by clinicians, with multiple manifestations and with no single symptom being sufficient or essential in its presentation. Manifestations include appearance (consistent or not with age), nutritional status (thin, weight loss), subjective health rating (health perception), performance (cognition, fatigue), sensory/physical impairments (vision, hearing, strength) and current care (medication, hospital). Although the early stages of the frailty process may be clinically silent, when depleted reserves reach an aggregate threshold leading to serious vulnerability, the syndrome may become detectable by looking at clinical, functional, behavioral and biological markers. Thus, a better understanding of these clinical changes and their underlying mechanisms, beginning in the pre-frail state, may confirm the impression held by many geriatricians that increasing frailty is distinguishable from ageing and in consequence is potentially reversible. We therefore provide an update of the physiopathology and clinical and biological characteristics of the frailty process and speculate on possible preventative approaches.
 ...
PMID:Frailty syndrome: a transitional state in a dynamic process. 1934 41

Autosomal dominant hypophosphatemic rickets (ADHR) is a rare disease, characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D(3) (calcitriol) levels. This syndrome involves rickets with bone deformities in childhood and osteomalacia, osteoporosis, articular and para-articular pain, and fatigue in adulthood. It is caused by mutations in a consensus sequence for proteolytic cleavage of the FGF23 protein. Normally, this protein actively regulates phosphate homeostasis. Here we report a Tunisian family in which one parent and three children show clinical and biological features of ADHR. Mutation analysis of the FGF23 gene finds a heterozygous substitution of the C at position 526 by a T (526 C --> T), leading to an amino acid replacement of the FGF23 protein (R176W) at position 176. This causative new mutation is located in the consensus sequence for the proteolytic cleavage domain. These results confirm the importance of this site in FGF23 function and its essential role in ADHR physiopathology.
 ...
PMID:An autosomal dominant hypophosphatemic rickets phenotype in a Tunisian family caused by a new FGF23 missense mutation. 1965 82

Hereditary forms of renal phosphate wasting have been studied thoroughly in the past years. X-linked Hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and autosomal recessive hypophosphatemic rickets (ARHR) are known genetic disorders in which a disturbance of phosphatonins is a causative factor in the pathogenesis. We describe a comparable but yet undescribed disorder in a family in which a 53 year old man presented with a spontaneous fracture after suffering for years with severe fatigue and musculoskeletal pains. A low serum phosphate was discovered. The two subsequent generations of this family developed the same symptoms but at an earlier age. Almost all family members have been investigated and the majority appears to have low bone density and/or renal phosphate wasting and/or low serum phosphate. Remarkably no rickets was found. No elevation of FGF23 or mutations in the gene encoding FGF23 were found. We believe this is a new familial disorder of bone metabolism and phosphate homeostasis in which a disturbance of bone modulators may play a central role.
 ...
PMID:A familial disorder with low bone density and renal phosphate wasting. 1971 54

The organ most frequently affected in mitochondrial disorders is the skeletal muscle (mitochondrial myopathy). Mitochondrial myopathies may be part of syndromic as well as non-syndromic mitochondrial disorders. Involvement of the skeletal muscle may remain subclinical, may manifest as isolated elevation of the creatine-kinase, or as weakness and wasting of one or several muscle groups. The course of mitochondrial myopathies is usually slowly progressive and only rarely rapidly progressive leading to restriction of mobility and requirement of a wheel chair or even muscular respiratory insufficiency. Frequently reported symptoms of mitochondrial myopathies are permanent tiredness, easy fatigability, muscle aching at rest or already after moderate exercise, muscle cramps, muscle stiffness, fasciculations and muscle weakness. The diagnosis is based on the history, clinical neurologic examination, blood chemical investigations, lactate stress test, electromyography, magnetic resonance imaging, magnetic resonance spectroscopy, muscle biopsy, biochemical investigations of the skeletal muscles, and genetic investigations. Only symptomatic therapy is available and includes physiotherapy and orthopedic supportive devices, diet, symptomatic drug therapy (analgetics, cramp-releasing drugs, antioxidants, lactate-lowering drugs, alternative energy sources, co-factors), avoidance of mitochondrion-toxic drugs, surgery (correction of ptosis or orthopedic problems), and invasive or non-invasive mechanical ventilation. General anesthesia needs to be performed in the same way as in patients with susceptibility for malignant hyperthermia.
 ...
PMID:[Mitochondrial myopathies]. 1989 Jul 72

Infection of the central nervous system with Nocardia sp. usually manifests as supratentorial abscesses. Supratentorial and cerebellar abscesses from infection with Nocardia sp. following immunosuppression with long-term corticosteroids for idiopathic thrombocytopenia (ITP) have not been reported. An 83 years-old, human immunodeficiency virus (HIV)-negative, polymorbid male with ITP for which he required corticosteroids since age 53 years developed tiredness, dyspnoea, hemoptysis, abdominal pain, and progressive gait disturbance. Imaging studies of the lung revealed an enhancing tumour in the right upper lobe with central and peripheral necrosis, multiple irregularly contoured hyperdensities over both lungs, and right-sided pleural effusions. Sputum culture grew Nocardia sp. Neurological diagnostic work-up revealed dysarthria, dysphagia, ptosis, hypoacusis, tremor, dysdiadochokinesia, proximal weakness of the lower limbs, diffuse wasting, and stocking-type sensory disturbances. The neurological deficits were attributed to an abscess in the upper cerebellar vermis, myopathy from corticosteroids, and polyneuropathy. Meropenem for 37 days and trimethoprime-sulfamethoxazole for 3 months resulted in a reduction of the pulmonary, but not the cerebral lesions. Therefore, sultamicillin was begun, but without success. Long-term therapy with corticosteroids for ITP may induce not only steroid myopathy but also immune-incompetence with the development of pulmonary and cerebral nocardiosis. Cerebral nocardiosis may not sufficiently respond to long-term antibiotic therapy why switching to alternative antibiotics or surgery may be necessary.
 ...
PMID:Cerebellar nocardiosis and myopathy from long-term corticosteroids for idiopathic thrombocytopenia. 2004 27

PURPOSE Effects of specific antineoplastic therapies on progression of cancer-associated wasting remain uncharacterized. We selected a targeted therapy, sorafenib, because of its reported association with weight loss. PATIENTS AND METHODS Patients with metastatic renal cell cancer (RCC) who were resistant to standard therapy (N = 80) received sorafenib 400 mg twice daily or placebo in a randomized, double-blinded clinical trial. Computed tomography image analysis, which has high precision and specificity for evaluation of specific muscles and adipose tissues, was used to define change in total skeletal muscle and adipose tissue. Results At inclusion, 51% of patients were overweight or obese (ie, body mass index [BMI] > 25 kg/m(2)). Only 5% were underweight. Advanced muscle wasting (ie, sarcopenia) was present in 72% of patients with BMI less than 25 and in 34% of those with a BMI greater than 25. Patients received placebo for an average of 6 months and received sorafenib for 1 year. Patients in the placebo group had stable body weight during 6 months (0.8 kg +/- 0.7 kg), with no significant alteration of muscle or fat. Patients who received sorafenib lost 2.1 kg +/- 0.6 kg (P < .01) in 6 months and lost 4.2 kg +/- 0.7 kg (P < .01) by 1 year. Sorafenib-treated patients lost skeletal muscle progressively at 6 months (decrease of 4.9%; P < .01) and 12 months (decrease of 8.0%; P < .01). CONCLUSION Sarcopenia is prevalent in patients with metastatic RCC and is an occult condition in patients with normal or high BMI. Muscle loss is specifically exacerbated by sorafenib, consistent with the evidence for a role of kinases in regulating muscle mass. Muscle loss is a sorafenib adverse effect that may relate to asthenia, fatigue, and physical disability.
 ...
PMID:Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study. 2008 39

Male hypogonadism is commonly diagnosed on the basis of subphysiological concentrations of androgen hormones, and is associated with many symptoms present in advanced cancer. Androgen deficiency might be an important cause of muscle wasting in both cancer cachexia and sarcopenia. We did a systematic review of the clinical association of male hypogonadism in advanced cancer. We searched PubMed, Medline, and Embase for publications on the relation between male hypogonadism and functional status, nutritional status, body composition, symptoms, and quality of life in patients with advanced cancer. Of 381 publications identified, six original articles were included. We found no definitive association between nutritional, functional, or quality-of-life characteristics and male hypogonadism. Possible associations between male hypogonadism and weight loss, low albumin, low-body cell mass index, low-peripheral fat and muscle mass, higher inflammation, higher pain, higher opioid consumption, worse scores for anxiety, depression, and emotional and functional well-being need to be confirmed by better designed studies. There is no clear epidemiological data to indicate whether male hypogonadism is independently associated with clinical and biological sequelae of cancer cachexia, such as higher inflammation, fatigue, and body wasting. Standardised kits sensitive to low concentrations of free-testosterone or bioavailable testosterone are needed to diagnose androgen deficiency in women. A clearer epidemiology of androgen deficiencies in advanced cancer will help determine which patients should receive testosterone-replacement therapy for alleviating cancer cachexia symptoms and improving quality of life.
 ...
PMID:Male hypogonadism associated with advanced cancer: a systematic review. 2054 64

Cancer anorexia-cachexia syndrome (CACS) is a lethal but poorly defined involuntary wasting disorder. Loss of skeletal muscle and fat distinguishes it from starvation. Cachexia has been described as a clinical syndrome since ancient times, and the poor prognosis has long been acknowledged. In this article we have reviewed historical perspectives on cancer cachexia, and commented on modern definitions. In cancer cachexia, most historical descriptions included anorexia, wasting and a pale complexion. Other associated symptoms, such as fatigue, early satiety and taste changes, were inconsistently described. Newer descriptions have not significantly expanded the clinical picture.Today, there is still no consensus definition, hindering research on early diagnosis and effective therapy. The language descriptors used to characterise the syndrome are important. For example, the word 'cachexia' itself may mislead; perhaps cancer-related wasting syndrome is more accurate. Cancer anorexia-cachexia syndrome is a disorder associated with high morbidity and mortality, and deserves greater attention in both clinical and translational research.
 ...
PMID:What is cancer anorexia-cachexia syndrome? A historical perspective. 2060 45

Four goldfish Carassius auratus morphotypes of similar length (50 mm): common (streamlined, full complement of paired and median fins, bifurcated caudal fin), comet ('common like' but with a long, deeply forked caudal fin), fantail (short, deep body with twinned caudal and anal fins) and eggfish (similar to the fantail but lacking a dorsal fin) were compared. Drag, steady swimming kinematics, energetics, fast-start performance, stability in yaw and roll and propulsive muscle ultrastructural characteristics were measured. A performance 'pairing' (common and comet; fantail and eggfish) was a recurrent theme for most performance variables. Fantail and eggfish drag were higher (requiring more thrust at any given velocity) than those for the more streamlined common and comet. This was reflected in kinematics; tailbeat frequency and stride length at any given velocity for the common and comet were lower and higher, respectively, than that of the fantail and eggfish. Common and comet fatigue times were not significantly different from those of their ancestor, crucian carp Carassius carassius, and higher than the fantail and eggfish. The cost of transport of the common and comet (c. 0. 6 mg O(2) kg(-1) m(-1)) was accurately predicted by the mass scaling relationship for fish, but values for the fantail and eggfish (c. 1. 3 mg O(2) kg(-1) m(-1)) were not. Rolling and yawing motions in eggfish (dorsal fin absent) during steady swimming were associated with significant energy losses. Eggfish maximum fast-start acceleration (c. 5 m s(-2)) was poor due to the absence of inertial and lifting contributions to thrust from the dorsal fin and energy wasting rolling motions. Common and comet fast-start performance (average velocity c. 0. 45 m s(-1), maximum velocity c. 1. 2 m s(-1), average acceleration c. 7. 5 m s(-2), maximum acceleration c. 35 m s(-2)) was similar to that of other locomotor generalists (e.g. rainbow trout Oncorhynchus mykiss). Artificially selected fishes can contribute to the understanding of form and movement in fishes and complement studies of the role of locomotor adaptations in natural systems.
 ...
PMID:Swimming in four goldfish Carassius auratus morphotypes: understanding functional design and performance employing artificially selected forms. 2073 59

The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the "Autophagy Paradox". We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. We have termed this new paradigm "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism" or "Battery-Operated Tumor Growth". In this sense, autophagy in the tumor stroma serves as a "battery" to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients-both effectively "starving" cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy, by the upregulation of natural endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy, by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor stroma. As such, an anti-cancer therapy that combines the alternating use of both autophagy promoters and autophagy inhibitors would be expected to prevent the onset of drug resistance. We also discuss why anti-angiogenic therapy has been found to promote tumor recurrence, progression and metastasis. More specifically, anti-angiogenic therapy would induce autophagy in the tumor stroma via the induction of stromal hypoxia, thereby converting a non-aggressive tumor type to a "lethal" aggressive tumor phenotype. Thus, uncoupling the metabolic parasitic relationship between cancer cells and an autophagic tumor stroma may hold great promise for anti-cancer therapy. Finally, we believe that autophagy in the tumor stroma is the local microscopic counterpart of systemic wasting (cancer-associated cachexia), which is associated with advanced and metastatic cancers. Cachexia in cancer patients is not due to decreased energy intake, but instead involves an increased basal metabolic rate and increased energy expenditures, resulting in a negative energy balance. Importantly, when tumors were surgically excised, this increased metabolic rate returned to normal levels. This view of cachexia, resulting in energy transfer to the tumor, is consistent with our hypothesis. So, cancer-associated cachexia may start locally as stromal autophagy, and then spread systemically. As such, stromal autophagy may be the requisite precursor of systemic cancer-associated cachexia.
 ...
PMID:The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox. 2105 47


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