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)

This study was performed to evaluate local tumour control and toxicity of chemoradiotherapy given to patients with primary or recurrent carcinoma of the anal canal. A total of 117 patients were admitted to the Norwegian Radium Hospital during the period of 1983-1989, of which 106 received a combination of radiotherapy (50 Gy to the pelvis) and chemotherapy (mitomycin C + 5-fluorouracil). Sixty-five percent of the patients with primary carcinomas presented with advanced tumours (T3 or T4). Good local tumor control was obtained as only 25% of the patients with advanced tumours (T3 and T4) and 7% of those with smaller tumours (T1 and T2) had a local relapse after treatment. Recurrent tumours following primary surgery did not respond as well; 50% of these patients still had carcinoma 1 month following therapy. All patients experienced acute toxicity (dermatitis/mucositis, diarrhoea and general fatigue), and 50% needed as split course. There was, however, no therapy-related mortality. Survival data seem promising, but further follow-up is necessary to make conclusions. Eight percent of the patients had serious anal insufficiency after treatment. We conclude that the present regimen provides good local tumour control and well-preserved anal function, but has considerable acute toxicity.
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PMID:Chemoradiotherapy of anal carcinoma: tumour response and acute toxicity. 842 94

Disinfectant surveys from responding members of the American Society of Postanesthesia Nurses were divided into two groups based on whether or not they considered themselves to be exposed to disinfectants in their work environment. Their survey responses were then compared with those obtained previously from members of the Society of Gastroenterology Nurses and Associates, Inc., who were regularly exposed to 2% alkaline glutaraldehyde in the work setting. There were significant differences among the groups in the percentage of respondents who reported having headaches, eye irritations, respiratory problems, shortness of breath, rashes, memory loss, mood swings, and fatigue. These findings support the association of these complaints with 2% alkaline glutaraldehyde exposure. In contrast, there were no significant differences among the groups in the percentage of respondents who reported having asthma, rhinitis, chest pain, nausea, diarrhea, muscle/joint pain, visual disturbances, or dermatitis.
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PMID:Society of Gastroenterology Nurses and Associates, Inc. (SGNA) Endoscopic Disinfectant Survey results compared with control group. 902 1

An increasing number of persons say that they get cutaneous problems as well as symptoms from certain internal organs, such as the central nervous system (CNS) and the heart, when being close to electric equipment. A major group of these patients are the users of video display terminals (VDTs), who claim to have subjective and objective skin- and mucosa-related symptoms, such as pain, itch, heat sensation, erythema, papules, and pustules. The CNS symptoms are, e.g. dizziness, tiredness, and headache. Erythema, itch, heat sensation, edema and pain are also common symptoms of sunburn (UV dermatitis). Alterations have been observed in cell populations of the skin of patients suffering from so-called "screen dermatitis" similar to those observed in the skin damaged due to ultraviolet (UV) light or ionizing radiation. In "screen dermatitis" patients a much higher number of mast cells have been observed. It is known that UVB irradiation induces mast cell degranulation and release of TNF-alpha. The high number of mast cells present in the "screen dermatitis" patients and the possible release of specific substances, such as histamine, may explain their clinical symptoms of itch, pain, edema and erythema. The most remarkable change among cutaneous cells, after exposure with the above-mentioned irradiation sources, is the disappearance of the Langerhans' cells. This change has also been observed in "screen dermatitis" patients, again pointing to a common cellular and molecular basis. The results of this literature study demonstrate that highly similar changes exist in the skin of "screen dermatitis" patients, as regards the clinical manifestations as well as alterations in the cell populations, and in skin damaged by UV light or ionizing radiation.
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PMID:Skin changes in "screen dermatitis" versus classical UV- and ionizing irradiation-related damage--similarities and differences. 941 15

A 47-year-old woman visited a clinic with dyspnea which had continued for two months and was followed by general fatigue and fever. Antibiotics were not effective. Edematous erythema occurred on her face, elbows, knees and feet, and she entered our hospital. A skin biopsy revealed interface dermatitis with severe edema and mucinosis in dermis. Diffuse bilateral infiltration was observed in the chest X-ray, and laboratory findings showed increased LDH, GPT, GOT and CPK. No antinuclear factor was detected. Her respiratory condition rapidly worsened, and she died eight days after hospitalization in spite of corticosteroid pulse therapy. The autopsy revealed that the main cause of death was diffuse alveolar damage (DAD). Interstitial pneumonia related to dermatomyositis is not histologically uniform; the response to the therapy depends on its histological type. The patients with dermatomyositis who have poor prognosis are clinically characterized by acute onset with general symptoms and less pronounced muscle weakness; they generally show DAD in their lungs. We need to establish a simple method for distinguishing histological types of interstitial pneumonia and adequate therapy for each one.
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PMID:An autopsy case of dermatomyositis with rapidly progressive diffuse alveolar damage. 951 7

Between April 1993 and June 1994, 29 patients (pts) with unresectable, locally advanced, or metastatic non-small cell lung cancer were treated with a combination of p.o. trans-retinoic acid (TRA), 150 mg/m2/day, in three divided doses and s.c. IFN-alpha, 3 x 10(6) units/day. The age range was 41-80 years (median, 63 years). The Eastern Cooperative Oncology Group performance status was 0-1 (24 pts) and 2 (5 pts). Pts had advanced disease, refractory to conventional therapy (5 stage IIIB and 24 stage IV). Twenty-one pts had adenocarcinoma, six had squamous cell carcinoma, and two had large cell carcinoma. Only 3 pts completed 8 weeks of treatment, requiring neither interruption nor dose modification. Fatigue occurred in 88% of pts. A syndrome complex consisting of dry oral and nasal mucosa, recurrent sinus infections, and epistaxis occurred in 64% of pts. Grade II/III dermatitis was seen in 52%. Severe scrotal dermatitis was seen in 7 pts (47% of 15 males). Hypertriglyceridemia was moderate/severe in 11 pts, and 3 pts required gemfibrozil for levels up to 1660 mg/dl. Hematological toxicity was not encountered, and none of the pts had leukocytosis. One pt died with complications of myocardial infarction while on TRA/IFN-alpha. Twenty-five pts had more than 2 weeks of treatment and are evaluable for response; two pts died early with complications of cancer, and two pts declined to continue after only 3 and 5 days of treatment. Final assessment of response was by accepted clinical and radiological criteria at 8 weeks. There have been four objective responses: complete response, 2 (18+ and 17 months) and partial response, 2 (7 and 14 months). Responses were observed in all histologies. Combined differentiation treatment with TRA/IFN-alpha has modest but objective activity in non-small cell lung cancer. Toxicity is considerable. Additional studies to elucidate the biological basis of TRA/IFN-alpha and to define prognostic parameters predicting response are needed.
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PMID:Phase II study of all-trans-retinoic acid and alpha-interferon in patients with advanced non-small cell lung cancer. 981 69

5-Fluorouracil (5-FU) is an effective enhancer of radiation therapy (RT) in head and neck cancers. Due to rapid, predominantly hepatic metabolism by dihydropyrimidine dehydrogenase (DPD) and suggested clinical benefit from prolonged drug exposure, 5-FU is commonly given by continuous infusion. Eniluracil is a novel DPD-inactivator designed to prolong the half-life of 5-FU and provide sustained plasma concentrations of 5-FU with oral dosing. We conducted a Phase I study of the safety and efficacy of eniluracil given with oral 5-FU in patients receiving concurrent RT for recurrent or advanced squamous cell carcinomas of the head and neck. Thirteen patients with recurrent, metastatic, or high-risk (defined as an expected 2-year survival rate of <10%) head and neck cancer were enrolled and treated with concomitant chemoradiotherapy on an every-other-week schedule. Eniluracil at a fixed dose [20 mg twice a day (BID)] was given for 7 consecutive days (days 1-7). 5-FU and RT were given on 5 consecutive days (days 2-6). One patient was treated with once-daily RT (2.0 Gy fractions). The remaining patients received hyperfractionated RT (1.5-Gy fractions BID). The initial dose of 5-FU was 2.5 mg/m2 given BID. Dose escalation in patient cohorts was scheduled at 2.5-mg/m2 increments, with intrapatient dose escalation permitted. Lymphocyte DPD activity and serum 5-FU and uracil concentrations were monitored during two cycles. DPD activity was completely or nearly completely inactivated in all patients. Sustained, presumed therapeutic concentrations of 5-FU were observed at a dose of 5.0 mg/m2 given BID. Cumulative dose-limiting myelosuppression (both neutropenia and thrombocytopenia) was observed during the fourth and fifth cycles following administration of 5.0 mg/m2 5-FU BID. One patient died of neutropenic sepsis during cycle 4. Other late cycle toxicities included diarrhea, fatigue, and mucositis. Grade 3 mucositis was observed in 4 patients, but no grade 4 mucositis or grade 3 or 4 dermatitis was observed. A second patient death occurred during cycle 1 of treatment. No specific cause of death was identified. The study was subsequently discontinued. Cumulative myelosupression was the significant dose-limiting toxicity of oral 5-FU given with the DPD-inactivator eniluracil on an every-other-week schedule. Clinical radiation sensitization was not observed, based on the absence of dose-limiting mucositis and dermatitis. Alternative dosing schedules need to be examined to determine the most appropriate use of eniluracil and 5-FU as radiation enhancers.
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PMID:Phase I study of eniluracil, a dihydropyrimidine dehydrogenase inactivator, and oral 5-fluorouracil with radiation therapy in patients with recurrent or advanced head and neck cancer. 1003 77

Capecitabine is an orally administered fluoropyrimidine carbamate used for the treatment of paclitaxel- or anthracycline-refractory breast cancer. Capecitabine is metabolised via a 3-step process to the active agent fluorouracil. The final step of this process occurs preferentially in malignant tissue. In patients with paclitaxel-refractory breast cancer receiving capecitabine (2510 mg/m2/day for 2 weeks of a 3-week cycle) the objective tumour response rate was 20%. Disease progression occurred in 34% of patients and 40% had stable disease. In this trial, the median duration of response was 241 days. Disease progression or death occurred in 83% of patients, and median time to progression was 93 days. Median survival time was 384 days. In previously untreated patients with breast cancer, the response rate was higher and time to disease progression was longer after oral capecitabine (2510 mg/m2/day for 2 weeks of a 3-week cycle) than after intravenous cyclophosphamide, methotrexate and fluorouracil therapy. In clinical trials, generally gastrointestinal or haematological adverse events were reported most frequently. Other commonly reported events included hand-and-foot syndrome, fatigue, hyperbilirubinaemia, dermatitis and anorexia.
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PMID:Capecitabine. 1043 30

To evaluate the therapeutic effects and systemic toxicities of a capecitabine-based home therapy regimen in patients with metastatic renal cell carcinoma, 30 patients were enrolled in a phase II clinical trial. Treatment consisted of oral capecitabine combined with subcutaneous recombinant human interferon-alpha 2a, recombinant human interleukin-2 and oral 13-cis-retinoic acid. There were two (7%) complete responses (CRs) and eight (27%) partial remissions (PRs), for an overall objective response rate of 34% (95% CI 17-53%). Except one, all responses are ongoing, with a median duration of 9+ and 8+ months for CRs and PRs, respectively. Additionally, 12 patients (40%) reached stable disease. Eight patients (27%) showed continued disease progression despite treatment. Therapy was well tolerated and was given in the outpatient setting. Capecitabine-related World Health Organization (WHO) grade 2 and 3 toxicities were observed in five and two patients respectively, and were limited to fatigue, nausea/vomiting, diarrhoea, stomatitis, dermatitis and hand-and-foot syndrome. The substitution of capecitabine for 5-FU in the pre-existing biochemotherapy regimen did not result in a reduced therapeutic efficacy and showed significant anti-tumour activity in patients with advanced renal cell carcinoma.
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PMID:Capecitabine in the treatment of metastatic renal cell carcinoma. 1094 96

The aim of the present study is to determine the effect of blood lead on the health of industrial workers in United Arab Emirates (UAE). This is a cross-sectional pilot survey of blood lead levels (BLL) of 100 industrial workers (exposed) and 100 non-industrial workers (nonexposed), matched for age, sex and nationality selected from Al-Ain, Abu-Dhabi Emirate. Industrial workers had significantly higher mean of BLL (77.5+/-42.8 microg/dl and median 80.9 microg/dl) than non-industrial workers (19.8+/-12.3 microg/dl and median 11.0 microg/dl). In the present study, reported symptoms among industrial workers were strongly associated with BLL nausea/vomiting, muscular symptoms, dizziness, fatigue, irritability, memory disturbances, insomnia and allergic conjuctivitis, rhinitis and dermatitis. Furthermore, the present study revealed that industrial workers had higher prevalence of respiratory symptoms for phlegm, shortness of breath and diagnosed asthma. In conclusion, this study determined that occurrence of certain symptoms might be associated with lead exposure among industrial workers.
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PMID:A pilot survey of blood lead levels in various types of workers in the United Arab Emirates. 1168 41

Capecitabine is an orally administered prodrug of fluorouracil which is indicated in the US and Europe, in combination with docetaxel, for the treatment of patients with metastatic breast cancer failing anthracycline therapy, and as monotherapy for metastatic breast cancer resistant to paclitaxel and anthracycline therapy (US) or failing intensive chemotherapy (Europe). Capecitabine is also approved for use in metastatic colorectal cancer. Capecitabine is metabolically activated preferentially at the tumour site, and shows antineoplastic activity and synergy with other cytotoxic agents including cyclophosphamide or docetaxel in animal models. Bioavailability after oral administration is close to 100%. In patients with pretreated advanced breast cancer, capecitabine is effective as monotherapy and also in combination with other agents. Combination therapy with capecitabine 1,250 mg/m(2) twice daily for 2 weeks of every 3-week cycle plus intravenous docetaxel 75 mg/m(2) on day one of each cycle was superior to intravenous monotherapy with docetaxel 100 mg/m(2) on day one of each cycle. Capecitabine plus docetaxel significantly reduced the risks of disease progression and death by 35% (p = 0.0001) and 23% (p < 0.05), respectively, and significantly increased median survival (p < 0.05) and objective response rates (p < 0.01). Efficacy has also been demonstrated with capecitabine monotherapy and combination therapy in previously untreated patients in preliminary trials. The most common adverse effects occurring in patients receiving capecitabine monotherapy include lymphopenia, anaemia, diarrhoea, hand-and-foot syndrome, nausea, fatigue, hyperbilirubinaemia, dermatitis and vomiting (all >25% incidence). While gastrointestinal events and hand-and-foot syndrome occurred more often with capecitabine than with paclitaxel or a regimen of cyclophosphamide, methotrexate and fluorouracil (CMF), neutropenic fever, arthralgia, pyrexia and myalgia were more common with paclitaxel, and nausea, stomatitis, alopecia and asthenia were more common with CMF. The incidence of adverse effects and hospitalisation was similar in patients receiving capecitabine plus docetaxel and those receiving docetaxel monotherapy. In conclusion, capecitabine, an oral prodrug of fluorouracil which is activated preferentially at the tumour site, is an effective and convenient addition to the intravenous polychemotherapeutic treatment of advanced breast cancer in pretreated patients, and also has potential as a component of first-line combination regimens. Combined capecitabine plus docetaxel therapy resulted in similar rates of treatment-related adverse effects and hospitalisation to those seen with docetaxel monotherapy. Capecitabine is also effective as monotherapy in pretreated patients and phase II data for capecitabine as first-line monotherapy are also promising. While gastrointestinal effects and hand-and-foot syndrome occur often with capecitabine, the tolerability profile was comparatively favourable for other adverse effects (notably, neutropenia and alopecia).
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PMID:Capecitabine: a review of its pharmacology and therapeutic efficacy in the management of advanced breast cancer. 1251 69


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