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)

Since the discovery of melatonin as the principal hormone of the pineal gland in 1963, scientists have come to recognize that melatonin is a "master hormone" involved in the control of circadian rhythms and other biological functions. Although little is known about the influence of the pineal gland on motor control, important clues may be obtained by considering the pattern of melatonin secretion during the sleep cycles and particularly during rapid eye movement (REM) sleep when melatonin plasma levels are at their lowest. Since REM sleep is characterized by the occurrence of profound atonia which results in an almost complete paralysis of striated muscles, it is suggested that there might be a causal relationship between inhibition of melatonin secretion during REM sleep and the development of REM sleep atonia. This relationship is supported by the findings that melatonin regulates the activity of brainstem serotonin (5-HT) neurons which characteristically cease to fire during REM sleep and which faciliate the development of REM sleep atonia. Moreover, as the muscular atonia of REM sleep is physiologically and pharmacologically indistinguishable from cataplexy, it is possible that the pineal gland also influences to the development of cataplexy. Cataplexy is an ancillary symptom of narcolepsy and also occurs in multiple sclerosis (MS). In fact, it is believed that several of the neurological symptoms experienced by patients with MS such as weakness in the legs, feeling of collapsing knees, paroxysmal sudden falling, weakness in the neck, extreme fatigue, intermittent paresthesias, slurring of speech and intermittent blurring of vision, which often are exacerbated by stress and other emotional influences, may reflect the manifestations of cataplexy. Thus, several of the clinical features of MS may reflect a dissociated state of wakefulness and sleep and may improve by the administration of anticataplectic drugs.
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PMID:The pineal gland, cataplexy, and multiple sclerosis. 886 24

It is estimated that 10-20% of patients with multiple sclerosis (MS) have a chronic progressive (CP) course characterized by an insidious of neurological deficits followed by steady progression of disability in the absence of symptomatic remission. No therapeutic modality has shown specific efficacy in the treatment of patients with CP MS and there are no data to indicate that any pharmacologic or other modality alters the clinical course of CP MS. Treatment with picotesla electromagnetic fields (EMFs) is a highly effective modality for the symptomatic management of MS including the chronic progressive form. In addition, this treatment also appears to alter the natural course of the disease in CP patients. A 36 year-old man experienced, at the age of 31, insidious weakness in the legs and several months later developed difficulties with balance with ataxia of gait. His gait abnormality progressed slowly over the following years and at the age of 35 he was severely disabled with spastic paraparesis and ataxia using a rolling walker for ambulation and a scooter for longer distances. In particular, his disability had progressed rapidly over the six months preceding the initiation of treatment with EMFs. He as classified have CP MS and his prognosis was considered extremely unfavorable due to the degree of cerebellar and pyramidal tract involvement and the rapid course of deterioration. In July 1995 the patient began experimental treatment with EMFs. While receiving three treatment sessions a week over 12 months he experienced improvement in cerebellar functions such as gait, balance and tremor as well as bowel and bladder functions, mood, sleep and cognitive function and resolution of diplopia, blurring of vision, dysarthria, paresthesias in the hands, and fatigue. Most remarkably, there was no further progression of the disease during the course of magnetic therapy. This case illustrated that treatment with EMFs, in addition to producing symptomatic improvement, also reverses the clinical course of CP MS.
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PMID:Treatment with electromagnetic field alters the clinical course of chronic progressive multiple sclerosis--a case report. 900 66

Topiramate is a new antiepileptic drug which has recently become available in the United States and in a number of European countries. Pharmacological studies suggest that its mode of action is multifactorial and involves blockade of voltage-dependent sodium channels, potentiation of GABAergic transmission and inhibition of excitatory pathways through an action at AMPA receptor sites. Carbonic anhydrase inhibiting properties have also been demonstrated but they are considered not to be relevant to anticonvulsant activity. Topiramate is well absorbed from the gastrointestinal tract, peak plasma levels being usually attained in 2-3 hours. The drug is negligibly (9-17%) bound to plasma proteins and is eliminated partly by renal excretion in unchanged form and partly by oxidation and hydrolysis. In healthy volunteers, the half-life is about 20-30 hours, but elimination rate is accelerated in patients taking concomitant enzyme inducing drugs such as phenytoin, carbamazepine and barbiturates. Topiramate has no major effects on plasma levels of concurrent anticonvulsants, except for a rise in plasma phenytoin in occasional patients. In double-blind add-on trials in refractory partial epilepsy, a significant reduction in seizure frequency has been demonstrated in over 40% of topiramate-treated patients (vs about 10% of those treated with placebo), a response rate which compares favourably with that observed with other new antiepileptic drugs. Dosages found to be effective in add-on controlled trials range between 200 and 1000 mg day-1, although most patients are likely to benefit from receiving 400 mg day-1 or less. Preliminary data suggest that topiramate may be effective also in generalized epilepsies, but this needs to be confirmed in prospective studies. The most common adverse effects of topiramate are CNS-related and include dizziness, fatigue, visual disturbances, ataxia, mental slowing and impaired concentration. Paresthesias, anorexia, weight loss and increased risk of nephrolithiasis have been also reported. Many of these effects are related to dose and/or to rate of dose titration. Based on these data, topiramate appears to be a valuable new drug, whose main current indication is in the add-on management of refractory partial and secondarily generalized seizures. Studies on its potential-value as monotherapy are in progress.
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PMID:A pharmacological and clinical review on topiramate, a new antiepileptic drug. 926 38

Symptomatic hypotension during hemodialysis is a disabling complication in end-stage renal disease (ESRD) patients, especially in certain groups of patients who are at higher risk for this problem. Autonomic dysfunction is thought to play a significant role. We evaluated the efficacy of midodrine, an oral agent with selective alpha-adrenergic agonist activity used in the treatment of neurogenic orthostatic hypotension, on 10 hemodialysis patients with persistent intradialytic hypotension. The patients were given a dose of midodrine (mean dose, 5.5 mg; range, 5 to 10 mg) 30 minutes before each hemodialysis session. We compared blood pressure, pulse, body weight, and laboratory values for 10 consecutive dialysis sessions off and on midodrine therapy. There was a statistically significant improvement in lowest intradialytic systolic blood pressure (from 96.6 to 114.7 mm Hg; P < 0.001), lowest intradialytic diastolic blood pressure (from 53.2 to 59.0 mm Hg; P = 0.002), lowest intradialytic mean arterial pressure (from 67.7 to 77.6 mm Hg; P < 0.001), posthemodialysis systolic blood pressure (from 116.5 to 127.1 mm Hg; P < 0.001), posthemodialysis diastolic blood pressure (from 66.6 to 69.7 mm Hg; P = 0.040), and posthemodialysis mean arterial pressure (from 83.2 to 88.8 mm Hg; P = 0.001) after patients were placed on midodrine. There also was a small but statistically significant decrease in intradialytic pulse rate (from 86.3 to 81 beats/min; P = 0.021) and posthemodialysis pulse rate (from 87.4 to 81.7 beats/min; P = 0.024) after initiation of midodrine therapy. There was no significant difference in any of the prehemodialysis blood pressure measurements or pulse rate off or on midodrine therapy. The improvements in intradialytic and posthemodialysis blood pressure were associated with a uniform subjective improvement in symptoms associated with dialysis hypotension, such as cramps, fatigue, dizziness, and weakness. Other than scalp paresthesia in one patient, no adverse effects were noted. Our results suggest that the administration of a single dose of midodrine before hemodialysis is an effective therapy for intradialytic hypotension. A prospective trial with adequate patient numbers and long-term follow-up would be useful to evaluate this drug's efficacy and safety profile in patients with ESRD.
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PMID:Intradialytic hypotension: is midodrine beneficial in symptomatic hemodialysis patients? 939 20

Laparoscopic surgery provides patients with less painful surgery and a more rapid recovery, while requiring that surgeons work harder and in a more remote manner from the operating field. Cost-containment pressures on surgeons demand efficient surgery, whereas the increased technological complexity and sometimes poorly adapted equipment have led to increased complaints of surgeon fatigue and discomfort during laparoscopic surgery. There is, therefore, a need to evaluate the ergonomic integration and suitability of the laparoscopic operating room environment to address the issues of efficiency, safety, and comfort for the operating team. This approach is particularly important in the design of laparoscopic surgical instruments. A review of the literature on the biomechanics of laparoscopic surgical instrument use was combined with data from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Ergonomics Questionnaire and demonstration station. Laparoscopic instruments suffer from ergonomically inadequate handle designs and inefficient handle to tip force transmission, which lead to surgeon fatigue, discomfort, and hand paresthesias. Improvements in the design of laparoscopic instruments are needed to decrease the work and discomfort of tissue manipulation during video-endoscopic surgery.
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PMID:Surgical technology and the ergonomics of laparoscopic instruments. 956 72

Patients with colorectal carcinoma progressing after a 5-fluorouracil (5-FU)-containing regimen were eligible. One treatment cycle consisted of repeated administrations of 5-FU combined to folinic acid for six times and to oxaliplatin for three times over 50 days. 5-FU was given at the dose of 2.6 g/m2 as a continuous infusion over 24 h on days 1, 8, 22, 29 and 43 preceded by i.v. folinic acid (FA) at a dose of 500 mg/m2 over 1 h. Oxaliplatin was given 1 h after 5-FU at the dose of 130 mg/m2 over a 2 h infusion on days 1, 22 and 43. A total of 37 patients were treated according to this schedule. The rates of objective responses after the first and second treatment cycles were 28 and 17%, respectively, with rates of tumor growth control, i.e. including the stabilizations, of 55 and 28%. The median duration of response was 10 months and the median duration of stabilizations was 6 months. The median survival time from initiation of oxaliplatin-containing therapy is 10 months (2-28+). The median survival time from the diagnosis of metastatic disease is 24 months (2-40+). The main toxicities were leucopenia, diarrhea, fatigue and paresthesias. The combination of 5-FU/FA/oxaliplatin was well tolerated and appears as a meaningful therapy after failure of a previous 5-FU-containing treatment.
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PMID:Oxaliplatin combined to 5-fluorouracil and folinic acid: an effective therapy in patients with advanced colorectal cancer. 963 19

The authors prospectively assessed symptoms induced by the interruption of antidepressants in 16 patients (11 women and 5 men), aged from 33 to 85 years (mean = 52.4 +/- 16.4), treated with antidepressants since at least two weeks. All patients were free of alcohol abuse or dependence disorder and of other dependence to psychoactive substances. None of them presented medical illness. Diagnosis were made by separate evaluations by two authors and confirmed with a semistructered assessment instrument: the Schedule for Affective Disorders and Schizophrenia (Lifetime Version). All patients were submitted to a brutal discontinuation of their antidepressant agent. Patients were assessed twice, before the interruption of the antidepressant, and 72 hours later. Effects of antidepressant interruption were assessed by several means. Modification of anxiety and depression were evaluated using the Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Scale. Symptoms of withdrawal were assessed with Cassano and al.'s scale SESSH including an evaluation of anxiety, agitation, irritability, anergy, difficulty on concentrating, depersonalization, sleep and appetite disorders, muscle pains, nausea, tremor, sweating, altered taste, hyperosmia, paresthesias, photophobia, motor incoordination, dizziness, hyperacousia pain, delirium. Fourteen of the 16 patients (87.5%) presented modifications of their somatic or psychic state 3 days after the interruption of the antidepressant treatment. Most frequent symptoms were: increase in anxiety (31%), increase in irritability (25%), sleep disorders (19%), decrease of anergia and fatigue (19%). Mean scores of anxiety and depression were not significantly modified by the withdrawal. Following TCAs interruption (7 patients) most frequent symptoms were sleep disorders; increase in anxiety, nausea. Among patients withdrawn from SSRIs (6 patients), most frequent symptoms were increase in anxiety, increase in irritability, headache. Patients also presented a decrease of nausea, and of anorexia.
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PMID:[Prospective evaluation of antidepressant discontinuation]. 969 14

The purpose of this study was to determine whether psychological support associated with hormone replacement therapy (HRT) was more beneficial than replacement therapy alone. Our findings showed that HRT alone was more effective against vasomotor symptoms than HRT with psychological treatment (PT). While the combination of both treatment modalities (HRT + PT) was more effective against insomnia, nervousness, melancholy, fatigue, palpitations, and vertigo. Hormonal treatment alone and HRT with psychological treatment had little effect against paresthesia or tingling. Neither HRT alone nor HRT with psychological treatment was effective against joint and muscle pain or headache.
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PMID:Hormonal and psychological treatment: therapeutic alternative for menopausal women? 969 91

Allogeneic peripheral blood stem cell transplantation leads to an earlier engraftment compared to BMT. The feasibility, acceptance and long-term side-effects of G-CSF mobilisation of PBSC in unrelated healthy donors needs to be evaluated. Forty unrelated healthy donors received G-CSF in a dose of 10 microg/kg bodyweight for 5 days and two aphereses were performed. The donors were monitored prospectively. The data were compared to bone marrow harvests from unrelated donors. Almost all stem cell donors reported some side-effects due to Filgrastim application. Bone pain (32), headache (20), chest pain (two) and night sweats (one) were complained of. By taking analgesics, the pain was relieved in most cases. No donor discontinued the filgrastim application. Bone pain and headache resolved within 2-4 days after termination of Filgrastim application. There was, as expected, a seven-fold increase in the number of total WBCs. There were no significant changes of platelet counts during G-CSF application. After 4 weeks haemoglobin concentration and platelet counts showed no significant differences compared to baseline values. The aphereses were mostly tolerated very well. Eighteen donors reported paraesthesia, one donor developed dizziness, two complained of nausea and vomiting. There was a significant decrease in platelet count (242 before, 98 x 10(9)/l after aphereses). Autologous platelets were transfused after the second aphereses in four donors. These data were compared to data from 245 unrelated bone marrow donors, who had on average, 14 days bone pain and tiredness after donation. The G-CSF mobilisation and apheresis of peripheral blood stem cells is an alternative to traditional bone marrow harvesting in unrelated healthy donors. It is well tolerated and the duration of side-effects on average is shorter than after the surgical procedure. So far no long-term effects have been observed in the follow-up.
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PMID:Acceptance and feasibility of peripheral stem cell mobilisation compared to bone marrow collection from healthy unrelated donors. 971 88

This study was aimed to determine the activity and toxicity of combination paclitaxel and carboplatin in stage III B and IV NSCLC. Eligibililty required performance status. Paclitaxel was administered at a dose of 200 mg/m2, 3-hour infusion, followed by carboplatin at a tartgeted area under the concentration-time curve (AUC) of 6. Treatment was repeated at 3-week intervals for 6 courses. G-CSF 5 micrograms/kg was subcutaneously injected during subsequent courses if there was grade 3-4 leukopenia or granulocytopenia in the previous course. From August 1996 through June 1997, 15 patients were enrolled. The median age was 47 years (range 20-68 years), 60 per cent were female. 73.3 per cent had adenocarcinoma, and 66.7 per cent had stage III B disease. Eighty three courses were administered; 13 patients (86.7%) completed all six cycles. The objective response rate was 53.3 per cent, with 1 (6.7%) complete response and 7 (46.7%) partial responses. Pleural effusion, lung lesion and lymph node were the three most common sites that responded to chemotherapy. The major toxicity was myelosuppression. Grade 3 or 4 granulocytopenia, anemia and thrombocytopenia were observed in 18 per cent, 7.2 per cent and 1.2 per cent, respectively, of 83 courses administered. Four episodes of febrile neutropenia (4.8%) occurred in 3 patients. There was one episode of anaphylaxis during Paclitaxel infusion. Other common toxicities were mild myalgia, paresthesias, alopecia and fatigue. Most of the toxicities showed cumulative effect. Paclitaxel plus carboplatin is a moderately active regimen in advanced NSCLC. Toxicities of this regimen are well tolerated.
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PMID:Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer (NSCLC): a preliminary study. 980 67


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