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)

Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Although evidence supports a good safety profile for these agents, numerous tolerability issues have been associated with their use. This review provides an overview of the safety issues associated with the nitrogen-containing class of bisphosphonates and discusses the potential effect of these issues on adherence. The review specifically considers upper gastrointestinal (UGI) adverse events (AEs), renal toxicity, influenza-like illness, osteonecrosis of the jaw and evidence on how to treat or prevent these events. In clinical trials, UGI AEs, including severe events such as oesophageal ulcer, oesophagitis and erosive oesophagitis, have been reported at similar frequencies in placebo- and active-treatment arms. However, postmarketing studies have highlighted UGI AEs as a concern. These studies show that a significant portion of patients are less compliant with administration instructions outside strict clinical trial supervision, and when oral bisphosphonates are not administered as directed, patients are more likely to experience UGI AEs. Some clinical trials with oral bisphosphonates have suggested that a decrease in the frequency of administration may lead to improvement in gastrointestinal tolerability. In the authors' experience, the issue of UGI tolerability can be minimised by explaining to the patient and/or caregiver the importance of following administration instructions. Intravenous (IV) bisphosphonates have been recently approved for use in osteoporosis, offering an alternative regimen for patients with osteoporosis. Earlier generation IV bisphosphonates (e.g. etidronate) have been associated with acute renal failure. Alternatively, late-generation IV bisphosphonates (i.e. ibandronate) have shown a better safety profile in relation to renal toxicity. Influenza-like illness, often referred to as an acute-phase reaction, covers symptoms such as fatigue, fever, chills, myalgia and arthralgia. These symptoms are transitory and self-limiting and usually do not recur after subsequent drug administration. Symptoms of influenza-like illness have been associated with both IV and oral bisphosphonates. Osteonecrosis of the jaw has also been associated with IV bisphosphonate treatment, particularly in patients treated with high doses. A small number of patients with cancer and osteoporosis using oral bisphosphonates have also reported this AE. As osteonecrosis of the jaw is difficult to treat and is often associated with dental procedures and poor oral hygiene, preventive measures seem to be the best management option for patients taking bisphosphonates.Overall, the safety and tolerability profile of the nitrogen-containing bisphosphonates is good, and long-term treatment does not appear to carry a risk of serious AEs. By encouraging adherence to administration instructions physicians can minimise certain complications, such as UGI intolerability. By being aware of other potential safety issues, such as renal impairment, influenza-like illness and osteonecrosis of the jaw, physicians can detect these AEs early in the course of treatment.
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PMID:Safety considerations with bisphosphonates for the treatment of osteoporosis. 1772 68

The bis-phenazine XR5944.14 is a novel cytotoxic agent which intercalates into DNA and inhibits transcription. The objectives of this study were to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of XR5944.14 when given at doses ranging from 3.6 to 36 mg m(-2) every 3 weeks to patients with advanced tumours. Twenty-seven patients were treated with a total of 77 cycles. Dose-limiting toxicities occurred at doses > or =24 mg m(-2). Oral mucositis was the most common DLT. Two patients developed acute renal failure possibly related to the study drug. Other less-severe toxicities were diarrhoea, nausea, vomiting and fatigue. Haematological toxicity was mild. One patient showed an objective partial response. Pharmacokinetic analysis was performed during the first cycle of treatment and plasma was assayed for XR5944.14 using a validated liquid chromatography tandem mass spectrometry. The systemic exposure of XR5944.14 increased more than proportionally with increasing dose, with inter-patient variability increasing from dose level 24 mg m(-2) onwards. The lack of correlation between toxicity and PK values makes it difficult to recommend a dose for further study in phase 2 trials. More work is needed to explain the inter- and intra-individual variation in PKs and pharmacodynamics.
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PMID:First-into-man phase I and pharmacokinetic study of XR5944.14, a novel agent with a unique mechanism of action. 1784 59

Exertional heat illness is primarily a multi-system disorder results from the combined effect of exertional and thermoregulation stress. The severity of exertional heat illness can be classified as mild, intermediate and severe from non-specific symptoms like thirst, myalgia, poor concentration, hysteria, vomiting, weakness, cramps, impaired judgement, headache, diarrhea, fatigue, hyperventilation, anxiety, and nausea to more severe symptoms like exertional dehydration, heat cramps, heat exhaustion, heat injury, heatstroke, rhabdomyolysis, and acute renal failure. At its early stage, it is quite difficult to find out the severity of disease with manual screening because of overlapping of symptoms. Therefore, one need to classify automatically the disease based on symptoms. The 7:10:1 backpropagation artificial neural network model has been used to predict the clinical outcome from the symptoms that are routinely available to clinicians. The model has found to be effective in differentiating the different stages of exertional heat-illness with an overall performance of 100%.
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PMID:Backpropagation ANN-based prediction of exertional heat illness. 1804 Dec 90

A 46-year-old male subject performed excessive physical exertion during 4-6 h in a studio for body builders during 5 days. He was not practicing sport prior to this training and denied the use of any aiding substances. Despite muscle aching already after 1 day, he continued the exercises. After the last day, he recognized tiredness and cessation of urine production. Two days after discontinuation of the training, a Herpes simplex infection occurred. Because of acute renal failure, he required hemodialysis. There were absent tendon reflexes and creatine kinase (CK) values up to 208 274 U/L (normal: <170 U/L). After 2 weeks, CK had almost normalized and, after 4 weeks, hemodialysis was discontinued. Excessive muscle training may result in severe, hemodialysis-dependent rhabdomyolysis. Triggering factors may be prior low fitness level, viral infection, or subclinical metabolic myopathy.
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PMID:Severe rhabdomyolysis after excessive bodybuilding. 1809 94

Hypersensitivity to inulin (polyfructan) is a rare event; two cases of food allergy and some patients presenting with allergy and hypersensitivity after inulin infusion have been reported. An 11-year-old boy suffering from severe immunoglobulin (Ig)A nephropathy (IgAN) experienced both anaphylactic reaction and concomitant relapse of his nephropathy following inulin infusion, used for measuring glomerular filtration rate (GFR) 2 years after the appearance of his initial symptoms. Pruritus, wheezing and cough were observed during a first renal function test; results of prick and intradermal tests were negative for inulin. The patient presented with pallor, asthenia and oliguria when a second inulin infusion was performed under dexchlorpheniramine, leading to the immediate cessation of the infusion. He was readmitted 2 days later because of fatigue and nausea related to acute renal failure. A drug-induced acute interstitial nephritis was first suspected. However, due to the presence of macroscopic haematuria and proteinuria, a renal biopsy was performed and showed acute proliferative relapse of IgAN. The underlying mechanism of inulin hypersensitivity is not well known. We can hypothesize that inulin had activated the innate immune system. Inulin may, thus, have been the initiating event of the renal relapse, acting like an infection, in a patient with IgA-mediated immunological dysregulation.
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PMID:'Renal hypersensitivity' to inulin and IgA nephropathy. 1853 47

Bacteremia and/or toxic shock syndrome is a rare complication of streptococcal pharyngitis in adults. We describe a case of streptococcal toxic shock syndrome in a previously healthy young man who presented with fatigue, high fever, and suspected extensive streptococcal tonsillo-pharyngitis. Therapy consisted of high doses of antibiotics followed by treatment of consumptive coagulopathy, acute renal failure, and toxic shock syndrome. An attempt at hemodialysis and hemodiafiltration was ineffective, and the patient died 24 h after admission. The autopsy findings were compatible with the clinical diagnosis. The invasive group A streptococci isolated from the pharyngeal swab and blood cultures were identified as M1 and T1 type with pyrogenic exotoxin genes A and B. This was thus a definite case of streptococcal toxic shock syndrome complicated with multiorgan failure and lethal outcome. The benefit of intravenous immunoglobulins, surgical intervention, or clindamycin in survival improvement remains to be evaluated.
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PMID:Toxic shock syndrome due to group A streptococcal pharyngitis and bacteremia in an adult. 1878 44

A 57-year-old man was admitted to our hospital complaining of general fatigue and appetite loss. The initial chest radiograph showed infiltration in the left upper lung field. Cefozopran was administered. Concomitant diabetic ketoacidosis was treated with hydration and rapid-acting insulin. However he was intubated and ventilated because of deteriorated respiratory condition and ketoacidosis on the 3rd hospital day. Urinary legionella antigen was detected the same day, therefore ciprofloxacin and imipenem were initiated. On the 4th hospital day, he developed acute renal failure and was treated with continuous hemodiafiltration. In addition, he developed adult respiratory distress syndrome on the 6th hospital day, therefore siveletat sodium was given. The patient gradually began to improve and was extubated on the 17th hospital day. After that he was transferred to the metabolic ward on the 24th hospital day for control of his diabetes mellitus. Despite the severe complications in his clinical course, including diabetic ketoacidosis, acute renal failure and ARDS, detection of Legionella pneumophila by a urinary antigen test, Gimenez stain and sputum culture made prompt and proper administration of antibiotics possible, finally yielding a desirable outcome.
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PMID:[A case of Legionella pneumonia with diabetic ketoacidosis rescued despite the development of acute renal failure and ARDS]. 1960 25

Bacteremia and/or toxic shock syndrome are rare complications of streptococcal pharyngitis in adults. This report describes a previously healthy young man with streptococcal toxic shock syndrome who presented with fatigue, high fever, and suspected extensive streptococcal tonsillopharyngitis. Treatment consisted of high-dose antibiotics followed by therapy for consumptive coagulopathy, acute renal failure, and toxic shock syndrome. An attempt at hemodialysis and hemodiafiltration was ineffective, and the patient died within 24 h of admission. The autopsy findings were compatible with the clinical diagnosis. The invasive group A streptococci isolated from the pharyngeal swab and blood cultures were identified as M1 and T1 types with pyrogenic exotoxin genes A and B. This was a definitive case of streptococcal toxic shock syndrome complicated with multiorgan failure and fatal outcome. The benefits of intravenous immunoglobulins, surgical intervention, or clindamycin for improving survival remain to be evaluated.
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PMID:Toxic shock syndrome due to group A streptococcal pharyngitis and bacteremia in adults. 1981 63

A 70-year-old woman was referred and admitted to our hospital with fever of unknown etiology. She had a past medical history of pulmonary tuberculosis. Ten weeks before admission she was diagnosed with acute renal failure caused by crescentic glomerulonephritis. Oral steroid therapy was not effective and she required dialysis. On admission, she was started on empiric antibiotic treatment, with the suspicion of bacterial infection. On the 3rd hospital day, she developed sudden hypotension and underwent direct hemoperfusion with a polymyxin B immobilized fiber. Soon after, her blood pressure normalised. Her inflammatory level apparently then improved in terms of white blood cell count and C-reactive protein, although severe fatigue and liver dysfunction persisted. On the 17th hospital day, her blood pressure went down again, accompanied by progressive pancytopenia and significant increase in serum vitamin B12, lactate dehydrogenase and uric acid. The patient was transmitted to the intensive care unit where she received bone marrow aspiration. The result revealed marked hemophagocytosis. Suspecting lymphoma-associated hemophagocytic syndrome (HPS), we administered high-dose steroid and combination chemotherapy. The treatment had no effect, and the patient died on the 21st hospital day. The autopsy demonstrated a large number of tuberculous bacilli, marked hemophagocytosis and necrosis without granuloma formation in multiple organs, leading to the pathological diagnosis of tuberculosis-associated HPS. Tuberculosis in one of the major causes for morbidity and mortality in hemodialyzed patients. It often shows atypical clinical manifestation and is difficult to diagnose. HPS in general runs a mild course unless it is lymphoma or EB virus-associated. This case seemed like bacterial infection improved with antibiotics but turned out to be a rapidly progressive tuberculosis-associated HPS. A careful examination and extensive laboratory workup is necessary to rule out tuberculosis, particularly in patients undergoing hemodialysis.
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PMID:[Case of tuberculosis-associated hemophagocytic syndrome in a hemodialysis patient under steroid therapy]. 1999 90

Historically, the milk-alkali syndrome developed as an adverse reaction to the Sippy regimen of milk, cream and alkaline powders as treatment for peptic ulcer disease. The classic description includes hypercalcemia, metabolic alkalosis, and renal failure. Over the past 20 years, milk-alkali syndrome has had a resurgence, as consumption of supplements containing calcium has increased. A 46-year-old man presented to the emergency department after outpatient labs to evaluate his fatigue. He was found to have acute renal failure and hypercalcemia (total serum calcium was 15.9 mg/dL). Subsequent laboratory evaluation excluded both hyperparathyroidism and malignancy as causes. A detailed history led to the diagnosis of milk-alkali syndrome. With hydration and cessation of calcium carbonate ingestion, his renal function and serum calcium levels returned to normal. Physicians should have a high index of suspicion for milk-alkali syndrome in patients with hypercalcemia. Milk-alkali syndrome is no longer a merely a historical curiosity; it is currently the third most common cause of hypercalcemia.
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PMID:Hypercalcemia and acute renal failure in milk-alkali syndrome: a case report. 2010 39


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