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)

Carpal tunnel syndrome is well known to be associated with hypothyroidism, but other mononeuropathies have been rarely reported. We report a 65-year-old male who showed right deep peroneal nerve palsy caused by hypothyroidism. The patient was admitted to our hospital because of general fatigue and right drop foot. On admission, bilateral pretibial pitting edema was observed, predominant on the right side. There was no muscle contraction in the right anterior tibial muscle and extensor hallucis longus in addition to slight weakness of the proximal muscles; whereas, muscle atrophy of the anterior tibial muscle was not noted. There was no sensory disturbance. On an electrophysiological examination, there was no muscle action potentials by the stimulation of the right deep peroneal nerve. Other nerves showed normal results both in the conduction velocity and in the compound action potential. Two months after the administration of levothyroxine sodium (0.025 mg/day), the right deep peroneal nerve palsy was completely recovered, associated with disappearance of pretibial edema. It is not yet determined which of axonopathy or demyelination is dominantly responsible for neuropathy associated with hypothyroidism. These results suggested a conduction block in deep peroneal nerve associated with focal edema. It is necessary to consider hypothyroidism as well as trauma, diabetes mellitus, and vasculitis when investigating mononeuropathy of deep peroneal nerve.
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PMID:[Deep peroneal nerve palsy associated with hypothyroidism]. 839 65

Following a previous EORTC GU-Group study, in which linomide showed some activity in poor prognosis patients, this study was initiated to determine the effect of linomide in more favourable patients. 35 patients with metastatic renal cell carcinoma with good prognostic factors, i.e. good performance status, prior nephrectomy, no prior systemic therapy, and no liver, bone or brain metastases, were treated with linomide, a quinoline derivative with immunomodulating properties, at a dose of 10 mg daily, after an initial dose escalation during the first 4 weeks of treatment. In 29 evaluable patients, no responses were observed (95% confidence interval 0-10%). Best overall response was no change in 9 patients, for a median duration of 4 months. Linomide in this schedule was poorly tolerated, with 17% (6 patients) of patients being withdrawn and 23% (8 patients) having dose reductions due to adverse events, mostly influenza-like symptoms of myalgia, arthralgia and fatigue. Several cases of pericarditis and neuropathy were observed. In spite of selection of favourable prognosis patients and an optimal daily dosing schedule, linomide was not an effective treatment in renal cell carcinoma. In view of toxicity and lack of efficacy, there is no rationale in further testing the drug in this disease.
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PMID:EORTC phase II study of daily oral linomide in metastatic renal cell carcinoma patients with good prognostic factors. 915 37

The presence of antibodies to cardiolipin (ACL Abs) has been reported in some patients suffering from multiple sclerosis (MS), especially of the "neuromyelitic" type. In addition, bright T2-imaging foci (unidentified bright objects) are occasionally detected on brain magnetic resonance imaging (MRI) scans, in patients with antiphospholipid syndrome. From a cohort of 100 patients with a probable or definite diagnosis of MS according to Poser's criteria, we isolated a subgroup of 20 patients (8 males and 12 females) consistently positive for ACL Abs. These patients were followed up neurologically for 1 to 3 years and brain MRI scanning and a complete autoimmune screening were performed. Nineteen (19 of 20) of our patients had the classic neuroimaging features of MS (multiple white-matter T2 bright foci on the MRI scan). The most common neurological syndrome was chronic, slowly progressing myelopathy (presenting as myelopathy, neuromyelitis optica, or spinocerebellar syndrome; 15 of 20), and optic neuropathy (6 of 20). Headache was a dominant symptom in 8 of 20 patients. Less common symptoms included cognitive and psychiatric disorders and chronic fatigue. The mean levels of ACL Abs were 38.8+/-28.2 GPL (normal values up to 7.5). Oligoclonal bands in the cerebrospinal fluid were detected in only 3 of 20 patients. Patients were treated with acetylsalycilic acid and occasionally with short courses of steroids. The progression of the chronic myelopathic/spinocerebellar syndrome was slower than expected in MS (only 2 patients deteriorated whereas 4 improved during a mean follow-up period of 20.8+/-7.1 months). We conclude that patients with probable or definite diagnosis of MS, and consistently elevated levels of ACL Abs show a slower progression and some atypical (for MS) features, such as persistent headaches and absence of oligoclonal bands in the cerebrospinal fluid. In these patients, other, presumably vascular, mechanisms may be involved in the pathogenesis of the neurological symptoms. Therefore, management should include antiplatelet or even anticoagulant agents.
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PMID:A subgroup of multiple sclerosis patients with anticardiolipin antibodies and unusual clinical manifestations: do they represent a new nosological entity? 977 61

The present study is an evaluation of the quality of life of 32 patients following successful pancreatic transplantation. These patients were studied at from 6 months to 5 years post-transplantation. Over one-half of them were beyond the 21/2-yr mark. A questionnaire was developed that focused on symptoms of neuropathy, enteropathy, and retinopathy. All of the patients evaluated had completely normal carbohydrate metabolism, as evidenced by normal fasting blood sugars and hemoglobin A1C levels. Twenty-one of the 32 patients had symptomatic neuropathy pre-operatively, and 11 of these reported substantial subjective improvement. Eight remained unchanged and 2 became worse. Twenty-four patients had symptoms of enteropathy and 23 noted improvement post-transplantation. Retinopathy symptoms were not improved, but there was a suggestion that after 3 or 31/2 yr progression did not occur as rapidly as earlier. Virtually all of the patients had mood improvements and considerably less fatigue. We have determined that the risk of the procedure when receiving simultaneous renal and pancreas grafts is not significantly greater than that associated with a kidney transplant alone. Patients who are not uremic, either those with a successful kidney graft or those preuremic patients, are better candidates if symptoms are present. The risk of immunosuppression is insignificant in those patients who already have a successful renal transplant and are already on immunosuppressant drugs. Pancreatic transplantation can substantially improve the quality of life in diabetic patients, and should be considered as a therapeutic measure.
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PMID:Quality of life in diabetic recipients of kidney transplants is better with the addition of the pancreas. 1014 30

The aim of this study was to compare the efficacy and tolerability of docetaxel to methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure. A randomised multicentre trial was conducted in 283 patients with advanced breast cancer who had failed previous anthracycline treatment. Docetaxel at a dose of 100 mg/m2 every 3 weeks (n = 143) was compared with sequential methotrexate and 5-fluorouracil (MF; n = 139) given at day 1 and 8 every 3 weeks at dosages of 200 mg/ m2 and 600 mg/m2, respectively. After progression, crossover to the alternative treatment group was recommended. There was a significantly higher overall response rate in the docetaxel 42% (CR 8% + PR 34%) than in the MF arm 21% (CR 3% + PR 18%) (P < 0.001). The median time to progression (TTP) was 6.3 months in the docetaxel arm and 3.0 months in the MF arm (P < 0.001). Docetaxel also had a significantly higher response rate of 27% following crossover compared with MF (12%). Significantly more side-effects (leucopenia, infections, neuropathy, oedema, asthenia, skin, nail changes, alopecia) were seen in the docetaxel than in the MF group. However, grade 3 and 4 side-effects were infrequent with both drugs, with the exception of fatigue, alopecia and infections. Median overall survival (OS) including crossover phase was 10.4 months in the docetaxel and 11.1 months in the MF arm (P = 0.79). Based on the response rate and the primary endpoint of TTP, docetaxel is superior to sequential methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure.
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PMID:Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group. 1061 29

Patients with multifocal motor neuropathy may complain of muscle fatigue, even though the degree of conduction block assessed at rest has improved with treatment. To explore the mechanism involved, we examined changes in muscle force during maximum voluntary contraction (MVC) and monitored conduction block before and after MVC in five patients with multifocal motor neuropathy. The results were compared with those for the contralateral unaffected homonymous muscles. For one patient, who had bilateral involvement, a normal subject of a similar age and stature served as the control. Results of conduction studies were also compared with those from six patients with amyotrophic lateral sclerosis (ALS) with similar compound muscle action potential (CMAP) amplitudes after proximal stimulation. During MVC for 60 s, the affected muscles developed prominent fatigue; the force at the end of contraction compared with the initial force was significantly lower for the affected muscles [42 +/- 19% (mean +/- standard deviation) of the initial force] than for the control muscles (94 +/- 9%; P = 0.01). After MVC, the amplitude ratio of CMAPs after proximal versus distal nerve stimulation transiently decreased to 19 +/- 14% of that before MVC in the affected muscles, but not in the control muscles (94 +/- 3.8% of that before MVC) and in patients with ALS (95 +/- 6.7%). In one patient with a focal lesion in the forearm, nerve excitability was monitored at the lesion site before and after MVC for 120 s. There were significant increases in axonal threshold (approximately 48%) and supernormality (approximately 135%) immediately after MVC, suggesting that the axonal membrane had undergone hyperpolarization and, by extrapolation, that this had precipitated the conduction block. This study is the first to show that activity-dependent conduction block plays a role in human disease by causing muscle fatigue.
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PMID:Activity-dependent conduction block in multifocal motor neuropathy. 1090 90

A patient with painful neuropathy developed ocular, facial, and masticatory weakness and fatigue after 3 months of gabapentin (GBP) treatment (400 mg/day). An elevated level of serum acetylcholine receptor antibodies (AChR-Ab) was detected. The patient recovered following pyridostigmine therapy and withdrawal of GBP and, 2 years later, is practically asymptomatic despite positive AChR-Ab. Because of this clinical observation, we gave 150 mg/kg GBP to rats with experimental autoimmune myasthenia gravis (EAMG). Repetitive nerve stimulation at 3-Hz was performed, and the 5th/1st amplitude ratio was used to calculate the decremental response. In all EAMG rats, GBP induced a transient, abnormal decrement (7-20%) 90 to 240 min after administration. No decrement was induced by GBP in normal rats. Thus, GBP aggravates the decrement in EAMG. The mechanism involved in the hitherto unreported possible unmasking of myasthenia gravis (MG) by GBP is unknown. Gabapentin should be used with caution in this disease.
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PMID:Gabapentin may be hazardous in myasthenia gravis. 1091 56

The limited single-agent activity of cisplatin, its toxicity profile, and the inconvenience involved in hydrating patients has compelled researchers to investigate other treatments as possible alternative therapies in non-small cell lung cancer. More recently, interest has focused on the potential of nonplatinum combinations. Phase II studies show that the combination of docetaxel (Taxotere; Aventis, Antony, France) and gemcitabine is active in stage IIIB/IV non-small cell lung cancer not previously treated by chemotherapy. Response rates of up to 54% and a median survival time of 13 months have been reported. These data are comparable with the achievements of cisplatin-based combinations. A randomized phase II trial of docetaxel plus gemcitabine versus docetaxel plus cisplatin found that the two regimens were equally active in terms of response rate, median, and 1-year survival. However, the combination of docetaxel with gemcitabine produced significantly less neutropenia and nonhematologic toxicities. In combination, from 80% to 100% of the full single-agent gemcitabine and docetaxel doses can safely be administered once every 3 weeks. The combination of docetaxel plus vinorelbine is also active in non-small cell lung cancer and preliminary data suggest that this schedule with prophylactic filgrastim may optimize tolerability and dose intensity. In a phase II study using this approach, a confirmed response rate of 51% was obtained in 35 patients. At 12 months, the predicted median survival is 14 months and the predicted 1-year survival rate is 60%. Excessive lacrimation, fatigue, and onycholysis were cumulative toxicities. However, the incidence of mucositis and neuropathy was low with the combination of docetaxel and vinorelbine. Docetaxel combined with other new agents, particularly gemcitabine, may offer another useful alternative to cisplatin-based chemotherapy in patients with good performance status.
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PMID:Challenging the platinum combinations: docetaxel (Taxotere) combined with gemcitabine or vinorelbine in non-small cell lung cancer. 1128 20

Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy. Zidovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddl) and lamuvidine (3TC) cause neuropathy; stavudine (d4T) and fialuridine (FIAU) cause neuropathy or myopathy and lactic acidosis. The tissue distribution of phosphorylases responsible for phosphorylation of NRTIs relates to their selective tissue toxicity. The myopathy is characterized by muscle wasting, myalgia, fatigue, weakness and elevation of CK. The neuropathy is painful, sensory and axonal. In vitro, NRTIs inhibit the gamma-DNA polymerase, responsible for replication of mtDNA, and cause mtDNA dysfunction. In vivo, patients treated with AZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA depletion, deficiency of COX (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion, as determined with in vivo MRS spectroscopy, due to impaired oxidative phosphorylation. Animals or cultured cells treated with NRTIs develop neuropathy, myopathy, or cell destruction with similar changes in the mitochondria. There is evidence that the NRTI-related neuropathy is also due to mitochondrial toxicity. The NRTIs (AZT, ddC, ddl, d4T, 3TC) contain azido groups that compete with natural thymidine triphosphate as substrates of DNA pol-gamma and terminate mtDNA synthesis. In contrast, FIAU that contains 3'-OH groups serves as an alternate substrate for thymidine triphosphate with DNA pol-gamma and is incorporated into the DNA causing permanent mtDNA dysfunction. The NRTI-induced mitochondrial dysfunction has an influence on the clinical application of these agents, especially at high doses and when combined. They have produced in humans a new category of acquired mitochondrial toxins that cause clinical manifestations resembling the genetic mitochondrial disorders.
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PMID:Peripheral neuropathy and antiretroviral drugs. 1129 2

Vestar has asked for a second time for Food and Drug Administration (FDA) approval of DaunoXome, a liposomal daunorubicin, for the treatment of patients with systemic Kaposi's Sarcoma (KS) based on results from a large phase III trial. Overall response rates were lower than expected in this trial, with only 23 percent responding to DaunoXome, and there were slightly more than expected cases of reported neutropenia. However, incidence of toxicity such as hair loss, fatigue, and neuropathy were significantly lower. One other liposomal anthracycline, Doxil, has also been recommended for approval. No trials as yet have been done to compare the two drugs' effectiveness, although quality-of-life issues make these drugs attractive candidates.
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PMID:Liposomal chemotherapies. 1136 53


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