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 Phase I dose escalation and pharmacokinetic study of the alkylating cytotoxic agent treosulfan was conducted to evaluate the maximum tolerated dose and the dose-limiting toxicities in patients with advanced malignancies rescued by autologous peripheral blood stem cell transplantation. Twenty-two patients (15 ovarian and 7 other carcinomas/lymphomas) with a median age of 48 years were treated with 28 high-dose courses. Treosulfan was infused over 2 h at escalating doses from 20 to 56 g/m2, and pharmacokinetic parameters were analyzed. At 56 g/m2, three of six patients experienced dose-limiting toxicities: diarrhea grade III/IV in three patients; mucositis/stomatitis grade III in one patient; toxic epidermal necrolysis in one patient; and grade III acidosis in one patient. Other low-grade side effects, including erythema, pain, fatigue, and nausea/vomiting, were recorded. Two patients died within 4 weeks after treatment because of rapid tumor progression and fungal infection, respectively. Plasma half-life, distribution volume, and renal elimination of treosulfan were independent of dose, whereas the increase in area under the curve was linear up to 56 g/m2 treosulfan. The maximum tolerated dose of high-dose treosulfan is 47 g/m2. A split-dose or continuous infusion regimen is recommended for future high-dose trials. In consideration of antineoplastic activity and limited organ toxicity, inclusion of high-dose treosulfan in combination protocols with autologous peripheral blood stem cell transplantation seems worthwhile.
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PMID:Clinical phase I dose escalation and pharmacokinetic study of high-dose chemotherapy with treosulfan and autologous peripheral blood stem cell transplantation in patients with advanced malignancies. 1110 34

Erythema migrans, the characteristic skin manifestation of acute Lyme borreliosis, is a self-limited lesion. In contrast, acrodermatitis chronica atrophicans, the typical cutaneous manifestation of late Lyme borreliosis, is a chronic skin condition. In an effort to understand pathogenic factors that lead to different outcomes in dermatoborrelioses, skin biopsy samples from 42 patients with erythema migrans and 27 patients with acrodermatitis chronica atrophicans were analyzed for mRNA expression of five pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interferon-gamma, and interleukin-2) and two anti-inflammatory cytokines (interleukin-4 and interleukin-10) by in situ hybridization with cytokine-specific riboprobes. Among the 27 patients who had erythema migrans alone with no associated signs or symptoms, the major cytokines expressed in perivascular infiltrates of T cells and macrophages were the pro-inflammatory cytokine interferon-gamma and the anti-inflammatory cytokine interleukin-10. In the 15 erythema migrans patients who had associated signs and symptoms, including headache, elevated temperature, arthralgias, myalgias, or fatigue, a larger number of macrophages and greater expression of macrophage-derived pro-inflammatory cytokines, tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6, were also found. In comparison, infiltrates of T cells and macrophages in the skin lesions of acrodermatitis chronica atrophicans patients had very little or no interferon-gamma expression. Instead, they usually expressed only the pro-inflammatory cytokine tumor necrosis factor alpha and the anti-inflammatory cytokine interleukin-4. Thus, the activation of pro-inflammatory cytokines in erythema migrans lesions, particularly interferon-gamma, seems to be important in the control of the spirochetal infection. In contrast, the restricted pattern of cytokine expression in acrodermatitis chronica atrophicans, including the lack of interferon-gamma, may be less effective in spirochetal killing, resulting in the chronicity of this skin lesion. J Invest Dermatol 115:1115-1123 2000
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PMID:Differential expression of cytokine mRNA in skin specimens from patients with erythema migrans or acrodermatitis chronica atrophicans. 1112 Nov 50

The study objective was to demonstrate the safety of Streptococcus pneumoniae vaccine in 430 geriatric patients at high risk of infection. The reactions after inoculation were classified as follows: (1) Grade 1: slight pain at the site of injection; mild systemic fatigue to improve within 3 days. (2) Grade 2: symptoms of swelling, erythema, or pain lasting for more than 3 days; inability to move upper limb due to pain; systemic symptoms such as a temperature above 38 degrees centigrade. (3) Grade 3: reactions requiring immediate medical therapy. Seventy patients (16.3%) showed inoculation reactions, and 360 (83.7%) were asymptomatic. Of the symptomatic reactions, 50 (11.6%) were grade 1.17 (4.0%) grade 2, and 3 (0.7%) grade 3. About 5% of the patients with grade 1 and 2 reactions needed special management. One chronic heart failure patient complained of severe heart failure symptoms after inoculation.
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PMID:[Safety of and untoward reactions to 23-valent pneumococcal vaccine: a prospective study]. 1119 17

A 22-year old woman developed erythema in her hands. She also suffered from general fatigue and arthralgia. In July of 1992, she visited the dermatology clinic of Nagoya City University Hospital. We made a diagnosis of subacute cutaneous lupus erythematosus with thrombocytopenia and gave her 30 mg of prednisolone daily. Her conditions were improved and had been stable with 5 mg of prednisolone daily. In the winter of 1993, she developed ulcer in her fingers and soles. These lesions were associated with antiphosholipid syndrome. She complained of mild headache. She was examined by CT, MRI and single photon emission computerized tomography (SPECT) using N-isopropyl-p-[123I] iodoamphetamine (IMP). Low perfusion areas in the bilateral occipital lobes and the right temporal lobe were found in SPECT, although no abnormalities were detected by CT and MRI. Low perfusion areas in antiphospholipid syndrome might be caused by microarterial thrombosis, microvenous thrombosis or spasms, although they could be reversible. Ten mg of argatroban daily for one month improved cerebral low perfusion, headache, and skin lesions. In this case, argatroban was effective for both cerebral low perfusion and skin ulcer, which were related to antiphospholipid syndrome.
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PMID:[Improvement of cerebral perfusion with argatroban in a patient with antiphospholipid syndrome]. 1121 61

Eight genotypes of Borrelia burgdorferi are known currently. In Slovakia (Carpathian Euroregion) the most frequent genotypes are B. garini, B. afzelii, as well as B. valaisiana and B. lusitaniae. Infestation of the vector Ixodes ricinus is 3-30%. The most frequent early skin manifestation is erythema migrans (60-70%). Borrelia burgdorferi is suggested to be the causative agent in sclerodermia circumscripta, lichen sclerosus et atrophicus, maybe also in urticaria chronica, granuloma anulare, erythema anulare, erythema nodosum. It can be the causative agent also in neurological diagnoses as e.g. chronic oligosymptomatic encephalopathy, "sclerosis multiplex-like" syndrome and fatigue syndrome, arthralgia, myalgia, seronegative indifferentiated oligoarthritis and fibromyalgies. The serological diagnosis has to be coincide with clinical findings. Used serological examinations are ELISA, Immunoblot, indirect immunofluorescence examination. PCR is an important contribution in examination of synovial fluid (85% detection) and cerebrospinal liquor (24-100%). The importance of PCR is stressed in cases with mixed infections by several borrrelia genotypes. The first line treatment includes doxyciclin, amoxicilin, and erythromycin. The second line includes macrolides, cephalosporines. New perspectives are ascribed to active immunisation with recombined antigen OsA (LYMErix, ImuLyme).
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PMID:[Skin manifestations of Lyme borreliosis--occurrence, diagnosis, therapy]. 1121 59

This trial was designed to study the efficacy and tolerability of azelastine in controlling symptoms of chronic idiopathic urticaria, using ebastine as validation group. Fifty-two adult patients were randomised to receive azelastine (4 mg), ebastine (10 mg) or 18 placebo for 21 days. Patients were required to visit the investigating physicians on three different occasions (days 0, 7 and 21). On each of these three study days, investigators assessed itching, wheals and erythema, based on a 4-point scale, and quality of life using a visual-analogue scale and subscale 9 of the Short Form 36 (SF-36) Health Survey. Patients entered daily assessments of itching on diary cards also using a 4-point scale. Furthermore, investigators assessed global efficacy and tolerability of the study medication on day 21 or upon premature discontinuation of the trial. Side effects and compliance were evaluated on each visit. A statistically significant reduction in itching was found for both active treatments compared with placebo. These improvements, which were statistically significant already after 1 day of treatment, continued over the course of 3 weeks. Additionally, both azelastine and ebastine were effective in improving symptoms such as wheals and erythema when compared to placebo. The quality-of-life parameters were unaffected by either treatment. Taste perversion (2 cases) and somnolence (1 case) were the only adverse drug reactions of azelastine. Ebastine, however, seemed to cause more often and more severe symptoms such as fatigue, sleepiness and asthenia. Global assessments of efficacy and tolerability performed by the investigators, also favoured azelastine. In conclusion, both azelastine and ebastine are effective and safe drugs, able to control symptoms of chronic idiopathic urticaria since the first day of treatment, and along a period of 3 weeks.
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PMID:Azelastine tablets in the treatment of chronic idiopathic urticaria. Phase iii, randomised, double-blind, placebo and active controlled multicentric clinical trial. 1131 66

A 69-year-old Japanese man suffered from bronchial asthma, atrial fibrillation, general fatigue, high fever, and weight loss of about 5 kg within a month. He also had intermittent claudication, a tingling feeling in his fingers and toes, and an ulcer on his toe. His laboratory data revealed leukocytosis with absolute eosinophilia. The patient was treated with predonisolone 30 mg daily. Although the ulcers healed once, the lesions recurred with tapering predonisolone. The patient visited us because of the ulcer on his toe. Physical examination showed a 2 cm ulcer surrounded by slight erythema on his right fourth toe. Magnetic resonance angiography detected tapering stenosis of the medium-sized arteries in both legs. A biopsy from his myocardium showed the infiltration of eosinophils into the myocardium. The neuron conduction rate of his lower leg was slower than that of the normal control, demonstrating mononeuritis. From these findings, we diagnosed this patient as Churg-Strauss syndrome.
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PMID:Churg-Strauss syndrome involving medium-sized arteries. 1134 69

A 50-year-old fisherman was stung in his right hand by a Great Weever fish (Trachinus draco). The crew did not have sufficient medical knowledge to adequately treat him on board. Severe pain, oedema of the hand, fever, vomiting and syncope occurred. Treatment with antibiotics, on board, after disembarkation and later in hospital for six days reduced the severity of the symptoms. However, two years after the accident, the patient still suffered from a dysfunction of the right hand as well as extreme fatigue and intermittent joint complaints. The symptoms mostly commonly arising from a Weever fish sting are: severe pain, local erythema and oedema. Systemic symptoms may sometimes occur: headache, syncope, bradycardia, fever and hypotension. The symptoms of continuous joint pain and severe fatigue following a Weever sting have not been previously described. The Weever fish venom contains a mixture of biogenous amines, of which some are known: 5-hydroxytryptamine, epinephrine, norepinephrine and histamine. The venom's composition has yet to be fully elucidated. In the event of a Weever fish sting, the first aid which should be given is: clean the wound and immerse the affected part of the body for at least 30 minutes in water which is as hot as the victim can tolerate (40-45 degrees C). Persons at risk from Weever fish stings are bathers, especially from the Lesser Weever fish (Echiichthys vipera), and sea fishermen. General practitioners and first aiders in coastal areas as well as sea fishermen should be informed about the first aid to be given in the event of a Weever sting.
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PMID:[Chronic pain and impairment of function after a sting by the great weaver fish (Trachinus draco)]. 1137 1

Hypericum Perforatum Extract is an extract of the capsules, flowers, leaves, and stem heads of Hypericum perforatum, commonly called St. John's Wort. Hypericum Perforatum Oil is the fixed oil from H. perforatum. Techniques for preparing Hypericum Perforatum Extract include crushing in stabilized olive oil, gentle maceration over a period of weeks, followed by dehydration and filtration. Propylene Glycol and Butylene Glycol extractions were also reported. The following components have variously been reported to be found in H. perforatum: hypericin, naphtodianthrones, flavonoids, terpene and sesquiterpene oils, phenylpropanes, biflavones, tannins, xanthones, phloroglucinols, and essential oils. Hypericum Perforatum Extract is used in over 50 cosmetic formulations and Hypericum Perforatum Oil in just over 10, both across a wide range of product types. Acute toxicity studies using rats, guinea pigs, and mice indicate that the extract is relatively nontoxic. Animals fed H. perforatum flowers for 2 weeks showed significant signs of toxicity, including erythema, edema of the portion of the body exposed to light, alopecia, and changes in blood chemistry. In a chronic study, rats fed H. perforatum gained less weight than control animals. Mixtures containing the extract and the oil were not irritants or sensitizers in animals. Because of the presence of hypericin, H. perforatum is a primary photosensitizer. In clinical tests, a single oral administration of Hypericum extract resulted in hypericin appearing in the blood. With long-term dosing, a steady-state level in blood was reached after 14 days. The polyphenol fraction of H. perforatum had immunostimulating activity, whereas the lipophilic portion had immunosuppressing properties. Mixtures of the extract and the oil produced minimal or no ocular irritation in rabbit eyes. Mutagenic activity in an Ames test was attributed to flavonols in one study and to quercitin in another, but other genotoxicity assays were negative. No carcinogenicity or reproductive and developmental toxicity data were available. A mixture of the extract and the oil was not irritating in clinical studies. Adverse reactions to Hypericum extract in the clinical treatment of depression include skin reddening and itching, dizziness, constipation, fatigue, anxiety, and tiredness. Absent any basis for concluding that data on one member of a botanical ingredient group can be extrapolated to another in a group, or to the same ingredient extracted differently, these data were not considered sufficient to assess the safety of these ingredients. Additional data needs include current concentration of use data; function in cosmetics; photosensitization and phototoxicity data using visible light; gross pathology and histopathology in skin and other major organ systems associated with repeated dermal exposures; dermal reproductive/developmental toxicity data; human skin irritation and sensitization data using the oil; and ocular irritation data, if available. Until these data are available, it is concluded that the available data are insufficient to support the safety of these ingredients in cosmetic formulations.
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PMID:Final report on the safety assessment of Hypericum perforatum extract and Hypericum perforatum oil. 1155 39

Postoperative radiotherapy (RT) forms an intrinsic part of breast conservation therapy, substantially reducing the risk of breast relapse. It is given 4-6 weeks postoperatively using medial and lateral beams to achieve a near homogeneous dose to the breast while minimising the dose to adjacent structures. Typically, a dose of 40 Gy in 15 daily fractions over three weeks or 50 Gy in 25 fractions over five weeks is given, with a boost of 10 Gy using low energy electrons or superficial X-rays. RT is delivered to the chest wall after mastectomy in patients with large tumours (> 5 cm), close surgical margins, or significant axillary node involvement and may result in an additional 10% survival benefit. Early complications of RT include tiredness, skin erythema and moist desquamation. Late reactions, breast fibrosis, telangiectases and peau d'orange are reduced if more treatment fractions are given. Lung irradiation is minimised by careful treatment planning and < 1% of patients experience radiation pneumonitis or pulmonary fibrosis. Patients with locally advanced breast cancer may be offered a combination of systemic therapy, endocrine, chemotherapy and radical RT. Preoperative systemic and radiation therapy reduces the mastectomy rate but at present does not improve survival. Those who are unfit for radical treatment and have large ulcerating or fixed cancers are offered either endocrine or cytotoxic therapy, depending upon the oestrogen receptor status, followed by RT, which is unlikely to cure but may achieve local control for a variable duration. RT forms part of the multidisciplinary approach to palliative treatment for metastatic disease. Bone metastases occur in 75% of women with metastatic disease and RT provides effective pain relief and reducing risk of pathological fractures. Patients with brain metastases need high-dose steroids followed by cranial RT.
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PMID:Radiotherapy for early and advanced breast cancer. 1177 Mar 58


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