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)

A 27-year-old man was admitted to our hospital with the complaint of general fatigue. He had cervical and mediastinal lymphadenopathy. Laboratory examination revealed anemia, hypergammaglobulinemia, and increased levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). A chest radiograph showed opacities in both lung fields. Pathological findings from thoracoscopic mediastinal lymph node and lung biopsies were compatible with multicentric Castleman's disease (MCD), plasma cell type with pulmonary involvement. Chemotherapy combined with radiation therapy resulted in no improvement of his lymphadenopathy and inflammatory symptoms. Eight mg/kg humanized anti-human IL-6 receptor antibody (tocilitumab) was thus administered biweekly. Soon after initiating the tocilitumab treatment, the patient's general fatigue disappeared, and anemia, CRP, ESR, hypergammaglobulinemia and lymphadenopathy all improved remarkably. Further treatment with tocilitumab for two years resulted in maintenance of this good response without any severe adverse events, but the pulmonary findings showed no obvious improvement. Tocilitumab therapy was effective in this MCD patient, however its influence on concurrent lung disease needs to be investigated further.
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PMID:[Effectiveness of long term administration of humanized anti-interleukin-6 receptor antibody (tocilizumab) for multicentric Castleman's disease with pulmonary involvement]. 1698 13

Polymyalgia rheumatica is a disorder that affects people over 50 years of age. The etiology of the disease has not been hitherto clarified exactly. Its incidence among people over 50 is in the range of 0.1-0.5%. The incidence rate peaks in the age group of 60-70 years. It is also found in younger people, but far less frequently. The diagnosis is based primarily on locomotor complains--namely on pronounced pain, morning stiffness of the shoulder girdle, pelvic girdle and neck. Complaints relating to the arms and legs (such as muscular weakness, oedema, tendonitis etc.) are also observed, however, in one third of the cases. The diagnostic criteria are defined empirically. Polymyalgia rheumatica was formerly considered to be a form of elderly onset rheumatoid arthritis. The progressive erosion process is absent in the case of polymyalgia rheumatica unlike in the case of rheumatoid arthritis. Numerous factors are known, which point to a link between polymyalgia rheumatica and giant cell vasculitis, arthritis, but the precise nature of this relationship remains unknown. Both conditions affect the same age group in the general population and they are even found--not infrequently--in the same patient. Polymyalgia rheumatica can be found in 40% of the patients suffering from arthritis while the histological examination detected mild vasculitis in approximately 10% of the patients suffering for "isolated" polymyalgia rheumatica. The response to be given to the acute phase is similar in both disorders. Scandinavian authors consider polymyalgia rheumatica as the appearance of generalised arthritis. Arthroscopic, nuclear magnetic resonance imaging as well as isotopic studies show unequivocally, that in the background of the osteo-muscular symptoms, complaints, inflammation is to be found partly of the joints but primarily that of the periarticular synovial structures. The above mentioned--dominant--proximal symptoms can often mask the distal locomotor disorders (pitting oedema of the hands and feet, tendonitis, tendosynovitis, carpal tunnel syndrome). The disorder may be accompanied by atypical generalised symptoms (loss of appetite, weight loss, fever, fatigue). An excellent indicators of the acute phase reactions are erythrocyte sedimentation rate, C-reactive protein and interleukin-6. These are suitable for monitoring the effectiveness of the therapy, for indicating a relapse/recurrence. It should be noted, that polymyalgia rheumatica may also be present if the erythrocyte sedimentation rate and C-reactive protein values are low. This disorder is also characterised by fast and effective response to corticosteroid, which should be administered for 1-2 years. In some individual cases a different dosage regime may be necessary: steroid administered in low dosage over a longer period of time. Administration of methotrexate and anti-tumor necrotic factor-alpha may also be considered as alternative or adjuvant therapy for lowering the quantity of corticosteroid. Further multicenter, double blind studies should, however, be performed on large number of patients in this regard.
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PMID:[Polymyalgia rheumatica]. 1713 99

Interest in the relationship between inflammation and oxidative stress has increased dramatically in recent years, not only within the clinical setting but also in the fields of exercise biochemistry and immunology. Inflammation and oxidative stress share a common role in the etiology of a variety of chronic diseases. During exercise, inflammation and oxidative stress are linked via muscle metabolism and muscle damage. Because oxidative stress and inflammation have traditionally been associated with fatigue and impaired recovery from exercise, research has focused on nutritional strategies aimed at reducing these effects. In this review, we have evaluated the findings of studies involving antioxidant supplementation on alterations in markers of inflammation (e.g., cytokines, C-reactive protein and cortisol). This review focuses predominantly on the role of reactive oxygen and nitrogen species generated from muscle metabolism and muscle damage during exercise and on the modulatory effects of antioxidant supplements. Furthermore, we have analyzed the influence of factors such as the dose, timing, supplementation period and bioavailability of antioxidant nutrients.
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PMID:The influence of antioxidant supplementation on markers of inflammation and the relationship to oxidative stress after exercise. 1715 94

We present the case of a 56-year-old woman with anti-glomerular basement membrane (anti-GBM) antibody disease accompanied by granulomatous reaction in the kidney. Three months prior to admission to our kidney center, she had suffered from interstitial pneumonia and had a slightly elevated level of MPO-ANCA (13 EU). Her serum level of creatinine was normal (0.72 mg/dl) but proteinuria (1+) and hematuria (2+, 1-4/HF) were present. She was admitted to our hospital because of general fatigue, loss of appetite, high fever (over 38.5 degrees C) and a rapid decline in renal function (creatinine 8.50 mg/dl). Hemodialysis therapy was started immediately after admission. The serological study was negative for MPO-ANCA and PR3-ANCA but positive for anti-GBM antibody (139 EU). Renal biopsy demonstrated necrotizing glomeruli, cellular crescents and grauloma formation with multinucleated giant cells. Immunofluorescence microscopy revealed linear staining of IgG and C3. We diagnosed graulomatous, crescentic and necrotizing glomerulonephritis, patho-logically. She was diagnosed as having anti-GBM antibody disease because alveolar hemorrhage was absent. Steroid therapy including methylprednisolone pulse therapy (500 mg/day, 3 days) and 2 courses of plasma exchange were effective in reducing the fever, anti-GBM antibody titer and C-reactive protein level. Her renal function recovered and she was able to quit hemodialysis therapy 68 days after the start of hemodialysis and she has shown no signs of pulmonary alveolar hemorrhage to date. The present case suggests that intensive therapy may restore renal function in anti-GBM disease even though renal function was sufficiently damaged and required hemodialysis therapy and active pathological changes were observed in renal biopsy specimens.
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PMID:Anti-glomerular basement membrane antibody disease with granulomatous lesions on renal biopsy. 1737 97

Since prozone is a well known phenomenon in the serologic diagnosis of Brucella infections, it is necessary to prepare higher serum dilutions in the standard tube agglutination (STA) test for the brucellosis suspected patients. However, due to limited economical support, the serum dilutions generally last at 1/320-1/640 titers in some laboratories in Turkey. In this report, a brucellosis case whose STA test was found negative until the titer of 1/1280, has been presented. A 36-year-old female was admitted to our hospital with the complaints of fever, sweating, fatigue, generalized arthralgia and weight loss, lasting for 45 days. Hepatosplenomegaly was detected in the physical examination, and laboratory tests yielded anemia, leucopenia, elevated erythrocyte sedimentation rate and high C-reactive protein levels. Although brucellosis was suspected, Brucella STA test was found negative at 1/640 titer. On the sixth day of admission, Brucella melitensis was isolated from her blood culture. Since a positive result at 1/40 titer was detected in Brucella STA test with the use of Coombs antiserum, the patient's serum was retested at higher dilutions than 1/640, and positive result was obtained starting from 1/1280 dilution and extended to 1/5120 titer. The patient was treated with rifampin and doxycyline and discharged with complete cure. In conclusion, in countries endemic for brucellosis, STA test should be performed at 1/1280 or higher titrations in suspected patients especially in the presence of negative culture results, for the prevention of false negative results due to prozone phenomenon.
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PMID:[A case of brucellosis presenting as high titer negative result by standard tube agglutination test]. 1742 66

Chronic inflammation often acts as a tumor promoter, resulting in aggressive cancerous growth and spread. Many of the same inflammatory factors that promote tumor growth also are responsible for cancer cachexia/anorexia, pain, debilitation, and shortened survival. A compelling case may be made for mounting an attack on inflammation with other anticancer measures at initial diagnosis, with the consequent probability of improving both patient quality of life and survival. High serum levels of the inflammatory marker C-reactive protein or fibrinogen and an elevated white blood cell count correlate with poor prognosis and may be used as a prognostic index to establish the need for nutritional/metabolic intervention. At the author's institution, a concerted effort is being made to screen all newly diagnosed patients with non-small cell lung cancer for the presence of nutritional problems, inflammatory markers, and related symptoms. Interventions include dietary counseling; nutritional and, if warranted, vitamin supplementation; exercise concordant with the patient's physical condition; a prescription for omega 3 fatty acids if inflammation is present, and general symptom management. To establish the value of early nutritional/metabolic intervention, clinical trials are needed that combine measures that combat cachexia and inflammation with first-line chemotherapy in patients who present with weight loss, fatigue, and deteriorating function.
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PMID:Cancer cachexia and targeting chronic inflammation: a unified approach to cancer treatment and palliative/supportive care. 1750 May 3

We report three cases of multicentric Castleman's disease (MCD) successfully treated with anti-interleukin-6 receptor antibody (tocilizumab). Tocilizumab was administered intravenously at a dose of 8 mg/kg every 2 weeks. In each case, tocilizumab alleviated symptoms, including generalized fatigue, pyrexia, and alleviated biochemical abnormalities, including anemia, hypoalbuminemia, hypergammaglobulinemia, and increased C-reactive protein (CRP). Side effects included hypercholesterolemia, acute pyelonephritis, mild inflammation of the parotid glands, and upper respiratory system inflammation. Other severe side effects were not observed. These results indicate that tocilizumab is effective for the treatment of MCD. This is the first report on tocilizumab efficacy for Castleman's disease after approval for use for Castleman's disease.
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PMID:Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease. 1754 Dec 33

A 56-year-old female non-smoker complained of general fatigue and pyrexia. Laboratory examination revealed elevation of white blood cells (WBC) 10200/microl and C-reactive protein (CRP) 13.3mg/dl. Chest radiograph showed bilateral patchy and ring-shaped consolidations in both lungs. Chest computed tomography (CT) revealed multiple round ground glass opacities fringed with consolidation, namely the "reversed halo sign". Transbronchial lung biopsy specimens showed polypoid granulation tissue in terminal air spaces, consistent with an organizing pneumonia pattern. Clinical findings suggesting collagen vascular diseases and drug induced lung diseases were not recognized, thus cryptogenic organizing pneumonia (COP) was diagnosed. High dose methylprednisolone therapy improved her condition, and the ring-shaped opacities on chest CT resolved. She relapsed twice during approximately five years after the disease onset. Chest CT at the recurrences revealed subpleural patchy consolidations without formation of the "reversed halo sign". The sign was originally supposed to be specific for cryptogenic organizing pneumonia. However, other diseases like sarcoidosis and paracoccidioidomycosis have been reported to show this sign. The meaning of the "reversed halo sign" should be examined based on the accumulation of more cases.
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PMID:[A case of cryptogenic organizing pneumonia showing reversed halo sign on computed tomography of the chest]. 1776 91

Under the common denomination of Systemic Immune-Metabolic Syndrome (SIMS), we grouped many symptoms that share a similar pathophysiologic background. SIMS is the result of the dysfunctional interaction of tumor cells, stroma cells, and the immune system, leading to the release of cytokines and other systemic mediators such as eicosanoids. SIMS includes systemic syndromes such as paraneoplastic hemopathies, hypercalcemia, coagulopathies, fatigue, weakness, cachexia, chronic nausea, anorexia, and early satiety among others. Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states, but treatment's compliance is generally poor. Preferentially, Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids, although their role in SIMS is unknown. The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach, some of the symptoms of the SIMS could be controlled. We exclusively evaluated 12 patients for compliance. Patients were assigned 1 of the 4 treatment groups (15-, 12-, 9-, or 6-g dose, fractionated every 8 h). For patients assigned to 15 and 12 doses, the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose. The maximum tolerable dose was calculated to be around 2 capsules tid (6 g of fish oil per day). A second cohort of 22 patients with advanced lung cancer and SIMS were randomly assigned to receive either fish oil, 2 g tid, plus placebo capsules bid (n = 12) or fish oil, 2 g tid, plus celecoxib 200 mg bid (n = 10). All patients in both groups received oral food supplementation. After 6 wk of treatment, patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite, less fatigue, and lower C-reactive protein (C-RP) values than their respective baselines values (P < 0.02 for all the comparisons). Additionally, patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values (P < 0.02 for all the comparisons). Comparing both groups, patients receiving fish oil + celecoxib showed significantly lower C-RP levels (P = 0.005, t-test), higher muscle strength (P = 0.002, t-test) and body weight (P = 0.05, t-test) than patients receiving fish oil + placebo. The addition of celecoxib improved the control of the acute phase protein response, total body weight, and muscle strength. Additionally, the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and/or celecoxib. This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor, some of the signs and symptoms associated with a SIMS could be ameliorated.
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PMID:Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. 1792 97

The majority of men with prostate cancer are aged > or =65 years. Men, as they age, are more likely to suffer from impaired physical function. The standard treatment for recurrent prostate cancer is androgen-deprivation therapy (ADT). Well-established toxicities from ADT include lean weight loss or sarcopenia, muscle weakness, fatigue, and reduced activity levels. Frailty is a term from geriatrics that describes older individuals with limited physiologic reserve who are at significant risk for adverse outcomes, including falls, disability, hospitalization, and death. An increasingly accepted definition of frailty is a syndrome in which > or =3 of the following are present: unintentional (lean) weight loss > or =10 pounds in the past year, weakness (measured by grip strength), slow walking speed, self-reported exhaustion, and low physical activity. This clinical syndrome overlaps closely with the known toxicities of ADT. In addition, alterations in the inflammatory system, neuroendocrine system, and energy production are associated with this syndrome, as evidenced by biomarkers such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. For this article, the authors reviewed the evidence for the effect of ADT on each of the 5 frailty components plus the identified biomarkers, and the evidence indicates that ADT may accelerate the development of frailty in vulnerable older men with prostate cancer. Given the association of frailty with important clinical outcomes such as hospitalization and death, this potential consequence of ADT should be considered carefully when initiating therapy in older patients with recurrent prostate cancer.
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PMID:Does androgen-deprivation therapy accelerate the development of frailty in older men with prostate cancer?: a conceptual review. 1796 Jun 9


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