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)

Cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisolone (CHOP) has for many years been the standard chemotherapeutic regimen for patients with aggressive non-Hodgkin's lymphoma. Published data for side effects experienced by patients undergoing CHOP chemotherapy in the treatment of non-Hodgkin's lymphoma are limited and inconsistent. No broad descriptive work appears to have been carried out. This study aimed to describe the range of problems experienced by patients receiving CHOP and to estimate incidence and severity of side effects over the treatment period. Data were collected at each treatment cycle via a 75-item self-report questionnaire, with severity of each side effect graded on a 5-point scale. The instrument has previously been shown to be reliable and valid. Nineteen participants received 99 cycles of CHOP and returned 74 questionnaires (response rate = 75%). Patients reported a total of 80 side effects. Alopecia was the most common problem, with all patients experiencing some hair loss by cycle 3. Fatigue was the second most common side effect (incidence = 77%) and taste change the third (incidence = 74%). Patients judged postchemotherapy nausea to be the "most troublesome" problem, followed by fatigue, taste change, constipation, and difficulty sleeping. Both nausea and fatigue were most problematic in the first part of the treatment course. These results indicate that patients receiving CHOP experience a wide range of problems, many of which merit further investigation.
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PMID:Side effects of CHOP in the treatment of non-hodgkin's lymphoma. 940 65

Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines in vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day.
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PMID:Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors. 953 30

In a post-marketing surveillance study of 752 patients suffering from urgent incontinence, mixed urgent-stress incontinence, reflex incontinence, urgency and enuresis were treated with propiverine hydrochloride. Clinical efficacy of propiverine hydrochloride was verified by the improvement of symptoms related to detrusor hyperactivity, hypersensitivity and hyperreflexia during a 12-week surveillance period: daytime and overnight urinary incontinence, as well as the frequency, nocturia, urgency in day time and at night decreased. These results are well demonstrated by decreased pad use and statistically significant decrease of Gaudenz urgency score during treatment, confirming the efficacy of propiverine hydrochloride already proved in clinical trials. The safety profile of propiverine hydrochloride displayed characteristic anticholinergic symptoms (dry mouth, accommodation disorders, constipation, tiredness, dizziness) with decreasing incidence during the 12-week treatment period. The residual urine volume decreased also. Serious adverse events were observed rarely and could be explained by the lack of consideration of contraindications, warnings and interactions with other drugs. The positive risk-benefit relationship of propiverine hydrochloride in the treatment of detrusor hyperactivity, hypersensitivity and hyperreflexia was reconfirmed in this post-marketing drug surveillance study.
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PMID:[Tolerance and effectiveness of propiverine hydrochloride in 752 patients with symptoms of detrusor hyperactivity and increased sensitivity and irritability of the urinary bladder: results of a study monitoring drug utilization]. 960 Jan 63

Benzylacyclouridine (BAU, IND 039655) is a potent and specific inhibitor of uridine phosphorylase (UrdPase; EC 2.4.2.3). This enzyme plays a major role in regulating uridine homeostasis and also catalyzes the conversion of fluoropyrimidine nucleosides to their respective bases. Inhibition of UrdPase enzyme activity 18-24 h after 5-fluorouracil (5-FU) administration increased plasma levels of uridine and enhanced the therapeutic index of 5-FU by rescuing normal tissues. Moreover, in vitro preclinical studies have also shown that inhibiting UrdPase enzyme activity by BAU prior to administration of 5-FU increased cytotoxicity in a number of human cancer cell lines. A series of preclinical studies was performed in dogs and pigs to evaluate the pharmacological and pharmacodynamic properties of BAU. These data showed a sustained elevation in plasma uridine concentration in both animal models. The rapid degradation of a tracer dose of uridine into uracil was virtually arrested by BAU administered both p.o. or i.v. The t1/2 of BAU was 1.8-3.6 h in dogs, with bioavailability levels of 85% (30 mg/kg) and 42.5% (120 mg/kg). In pigs, the half-life varied from 1.6 to 2.3 h, with a bioavailability of 40% at 120 mg/kg. The drug was distributed into most tissues with a tissue: plasma ratio of approximately 0.7. On the basis of these preclinical studies, we performed a Phase I clinical trial of BAU in patients with advanced cancer. Patients received 200, 400, 800, and 1600 mg/m2 BAU as a single oral dose. Toxicities included grade 2 anemia, grade 1 fever, grade 1 fatigue, grade 1 constipation, and grade 1 elevation in alkaline phosphatase; none of these toxicities were observed to be dose dependent. The maximum tolerated dose and dose-limiting toxicity were not reached at the doses given. BAU plasma concentrations and area under the curve correlated linearly with the oral dose level. The pharmacokinetics of BAU were consistent with a first-order clearance, with average peak concentrations ranging from 19 microM (200 mg/m2) to 99 microM (1600 mg/m2) and tbeta1/2 ranging from 3.0 to 3.9 h at the four dose levels. Compared with baseline plasma uridine, treatment of patients with 200, 400, 800, and 1600 mg/m2 BAU increased peak uridine concentrations by 120, 150, 250, and 175%, respectively. On the basis of this clinical study, the suggested Phase II starting dose of BAU in combination with 5-FU is 800 mg/m2. Studies combining BAU with 5-FU and incorporating appropriate molecular and biochemical end points to assess the effects of this drug combination on tumor and/or surrogate tumor tissue are under way.
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PMID:Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine phosphorylase inhibitor. 960 74

Selegiline (deprenyl), a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B) is widely used in the treatment of Parkinson's disease. As the first MAO-B inhibitor approved for the treatment of Parkinson's disease, concerns were raised about the safety of the drug based on the adverse effect profiles of older, nonselective MAO inhibitors. Unlike the nonselective MAO inhibitors, selegiline does not significantly potentiate tyramine-induced hypertension (the 'cheese effect') at the dosages (5 to 10 mg daily) used for the treatment of Parkinson's disease. Selegiline has been well tolerated when given alone. The most frequent adverse events seen during monotherapy have been insomnia, nausea, benign cardiac arrhythmias, dizziness and headache. When combined with levodopa, selegiline can potentiate the typical adverse effects of levodopa, if the dose of levodopa is not reduced sufficiently. Thus, the most common adverse effects associated with this combination are nausea, dizziness, fatigue, constipation and insomnia. At the later stages of Parkinson's disease when fluctuations in disability occur, peak dose dyskinesias, psychiatric complications like hallucinations and insomnia, and orthostatic hypotension are further potentiated by selegiline. Mortality was recently reported to be increased when selegiline and levodopa were given together in comparison with treatment with levodopa alone, but a large meta-analysis of 5 long term studies and 4 separate studies did not support this conclusion. Selegiline seems to be generally well tolerated in combination with other drugs. However, when pethidine (meperidine) has been given to patients who are receiving selegiline therapy, severe adverse effects have been reported. Thus, the concomitant use of these drugs is not recommended. A low tyramine diet is recommended if selegiline is used together with nonselective MAO inhibitors or the selective, reversible MAO-A inhibitor, moclobemide. Several adverse effects have been reported when fluoxetine and selegiline have been used together. A recent survey revealed that the incidence of a true serotonin syndrome is, however, very low with this combination. Concomitant use of selegiline and other selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) like citalopram, which have generally less interactions than fluoxetine, seems to be well tolerated. Nevertheless, caution is advised when combining a SSRI or a tricyclic antidepressant and selegiline.
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PMID:Safety of selegiline (deprenyl) in the treatment of Parkinson's disease. 967 55

Although controversial, opioid analgesics have been prescribed for patients with chronic facial pain. Based primarily on survey data and a few well-controlled clinical trials, long-term opioid treatment provides adequate pain reduction in 41% to 100% of patients with chronic nonmalignant pain. However, only 25% of chronic facial pain patients reported adequate pain relief with chronic opioid treatment. Work, home, and school function are generally reestablished or maintained during chronic opioid treatment, but 25% to 38% of patients remain dysfunctional, and one study indicated that 20% of patients became dysfunctional during treatment. Chronic opioid treatment is associated with many transient side effects; constipation, dizziness, nausea, vomiting, itching, and fatigue have been reported in 5% to 42% of patients taking opioids over 1 year. Although survey studies suggest that the risks of addiction are low in typical patients, drug abuse rates up to 17.3% and prescription abuse rates up to 27.6% were reported within groups of chronic opioid users. Chronic opioid use induces analgesic tolerance and physical dependence, which may result in a serious abstinence syndrome in users and children born to users. Chronic opioid use also may induce harmful immune system changes, diminish cognitive and motor function, and produce nociceptive hyperexcitability. This article shows that the use of long-term opioids for chronic facial pain is not justified based on the available data. Despite these perceived problems, there is anecdotal evidence that chronic facial pain patients will respond positively to opioid analgesics. In our experience, the pain assessment scale and a modification of the World Health Organization's three-step analgesic ladder, which prescribes nonopioid analgesics, can be the starting point for the successful management of chronic facial pain.
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PMID:The use of nonopioid drugs in management of chronic orofacial pain. 973 70

In this study, insomnia in 80-year-olds was related to medical, psychological and social factors. The data were based on examinations every year in people aged between 80 and 89 years. Of 333 people living in the city of Lund and born in 1908, 67% participated. Increased severity of insomnia was significantly associated with use of diuretics, other cardiovascular drugs, hypnotics and laxatives, and with nervousness, difficulty relaxing, anorexia, nausea, constipation, backache, feeling cold, sweating, loss of weight, dizziness, depression, general fatigue, exhaustion, angina pectoris, cardiac insufficiency, worsened objective and subjective health, presence of negative T-waves on ECG, anxiety, total life satisfaction, neuroticism, disbelief in a just world, feeling lonely and lower survival rates. Thus insomnia has widespread associations with different aspects of life in 80-year-olds.
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PMID:Insomnia in an 80-year-old population: relationship to medical, psychological and social factors. 978 73

One hundred patients admitted to an acute hospice/palliative care unit in a U.S. teaching hospital were evaluated using a standardized data acquisition tool that assessed the presence of physical symptoms and attitudes concerning admission to such a specialty unit. Patients entering the unit between June 1995 and October 1995 completed the tool within 24 hours of admission. Symptoms reported were fatigue in 81 patients, anorexia in 70, dyspnea in 61, xerostomia in 58, cough in 52, pain in 49, confusion in 37, depression in 37, constipation in 35, nausea in 30, insomnia in 23, and vomiting in 22. Of the 59 patients and family/friends that responded to the question "How do you feel about hospice care?", 53 gave a positive response. When asked about the best aspects of the unit, the most common response related to the care the patient and family received (23 responses, 39%). We conclude that patients admitted to an acute inpatient hospice/palliative care unit have multiple symptoms and a high degree of satisfaction with the environment.
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PMID:Symptoms and attitudes of 100 consecutive patients admitted to an acute hospice/palliative care unit. 984 25

The enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants (TCAs), and the frequency and type of adverse events, have made the treatment of depression in this group difficult. The selective serotonin reuptake inhibitors (SSRIs) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs. We compared the therapeutic actions and side effects produced by citalopram, the most selective SSRI available, with amitriptyline in a group of elderly patients (aged 65 and older) diagnosed with major depression. In a double-blind, double-dummy, parallel-group, multicenter comparison of citalopram (20 or 40 mg/day) and amitriptyline (50 or 100 mg/day), patients who did not respond to placebo during a 1-week single-blind phase were randomly assigned to receive citalopram or amitriptyline for 8 weeks. Efficacy measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAMD), and Clinical Global Impressions. Both drug treatments produced equivalent time-related declines in severity of depression, so that by 8 weeks slightly more than 50% of the patients in each group experienced marked recovery, defined as MADRS scores < or = 12. Amitriptyline produced a greater overall incidence of adverse events, including a significantly higher (P < 0.001) percentage of patients reporting dry mouth (34% vs. 7%), as well as a significantly higher (P < 0.02) incidence of somnolence. Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group. For only one event (nausea) did the citalopram group report a significantly greater (P = 0.012) incidence (12.8% vs. 4.8%). On the basis of these results, it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly. Because of its low incidence and low magnitude of side effects, citalopram seems especially useful in private practice.
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PMID:Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. 987 16

This longitudinal study examined relations among mood, coping, perceived stress, and side effects from chemotherapy in 50 individuals with stages III and IV adenocarcinoma of the lung over four consecutive combination chemotherapy courses. Results indicated that perceived stress was moderately high only at the time of pretreatment, and four coping strategies were used: seeking social support, planful problem solving, self-control, and positive reappraisal. No relations existed between coping strategies and side effects from chemotherapy, coping and perceived stress, mood and side effects, and perceived stress and side effects. Seven side effects occurred: leukopenia, decreased activity, nausea, loss of appetite, fatigue, constipation, and taste changes. In summary, receiving chemotherapy is stressful at the time of pretreatment, so nursing interventions need to be concentrated at that point.
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PMID:Temporal differences in coping, mood, and stress with chemotherapy. 1045 3


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