Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
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Symptoms of entrapment neuropathies are often intermittent, making the diagnosis a challenge; pain, paresthesias, exertional fatigue, weakness, and atrophy may be present. An accurate, detailed history and physical examination, often after activity, is essential to make an accurate diagnosis. Laboratory, radiographic, and electromyographic studies may be helpful, but are often normal. This article reviews the etiology, evaluation, and treatment of the most common upper extremity entrapment neuropathies related to sports participation. Most conditions respond to conservative measures of rehabilitation exercises, relative rest, correction of training and equipment errors, anti-inflammatory medications, and protective padding or bracing; occasionally surgical intervention is necessary.
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PMID:Entrapment neuropathies of the upper extremity. 1295 6

Fibromyalgia syndrome (FS) is characterized by widespread pain and tenderness at specific anatomic sites. Different theories have been proposed in the etiopathogenesis of this syndrome, and besides genetic, neuroendocrine, psychologic, and traumatic causes, infections have also been reported. The aim of the present study was to evaluate the presence of FS in patients with hepatitis C virus (HCV) infection. Ninety-five patients with chronic HCV infection and 95 healthy controls were enrolled in the study. The 1990 American College of Rheumatology classification criteria were used for the diagnosis of FS. Tender point count, pain intensity, sleep disturbance, stiffness, headache, paresthesia, fatigue, irritable bowel syndrome (IBS), and sicca- and Raynaud-like symptoms were assessed. Fibromyalgia was found in 18.9% of patients and 5.3% of healthy controls. Mean tender point count, pain intensity scored on a visual analog scale (VAS), sleep disturbance, stiffness, paresthesia, and fatigue were higher in the HCV group. No significant relationship was observed between the two groups regarding headache, IBS, and sicca- and Raynaud-like symptoms. In addition, mean tender point count and pain intensity scores were also significantly higher in HCV patients with FS than in control subjects with FS. All of the symptoms except stiffness were not statistically significant between the HCV and control groups with FS. Our results demonstrate a tendency toward higher prevalence of FS in patients with HCV infection. Besides various extrahepatic features, musculoskeletal disorders including fibromyalgia might be expected in the progression of HCV infection. Detailed examination of the patients helps to differentiate FS from other musculoskeletal complications of HCV infection. This will provide appropriate management approaches and better quality of life for them.
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PMID:Fibromyalgia syndrome in patients with hepatitis C infection. 1450 18

Previous epidemiological and clinical studies of humans exposed to polychlorinated biphenyls (PCBs) indicate that the majority of patients have neurological complaints (e.g., headache, vertigo, paresthesias, poor memory and concentration, fatigue, depression). Since only a small minority of PCB-exposed patients demonstrate abnormalities on objective neurological measures (e.g., CT-scans, EEC, nerve conduction velocity), it is particularly unfortunate that objective neuropsychological data has not been published to substantiate patient complaints. The present study provides neuropsychological test data on two patients exposed to PCBs. In both cases, PCB exposure is documented by an analysis of PCB levels in the patients' work environments. Despite the absence of abnormalities on CT-scans and EEC, both patients displayed a variety of cognitive deficits and emotional disturbance. Serial assessment of one patient with high blood levels of PCBs revealed a dementia (sharing certain features with Alzheimer's disease) and an organic affective syndrome. Assessment of a second patient exposed to PCBs (but with no detectable blood levels of PCBs) suggested that his cognitive impairments were not due to PCB exposure. The present study provides data which points to the importance and sensitivity of neuropsychological examination in cases of PCB-exposure.
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PMID:Dementia as a neuropsychological consequence of chronic occupational exposure to polychlorinated biphenyls (PCBs). 1458 22

Octreotide long-acting release (LAR) is a somatostatin analogue designed for once monthly intramuscular injection. As with endogenous somatostatin, octreotide LAR inhibits secretion of growth hormone (GH) as well as various other peptide hormones. In the treatment of acromegaly, octreotide LAR effectively controlled the secretion of GH and insulin-like growth factor-1 (IGF-1) in about 55-70% of patients (n > 100) who had previously been treated with somatostatin analogues, a similar degree of control to that observed with subcutaneous octreotide and lanreotide slow release (SR). Progressive control of serum levels of GH and IGF-1 was achieved with octreotide LAR in clinical studies of up to 4 years' duration. In addition, primary therapy with octreotide LAR provided effective control of GH and IGF-1 secretion, particularly in patients with a pretreatment GH level <20 microg/L. The percentage of patients achieving a target serum GH level of <2-2.5 micro g/L or normal IGF-1 levels was significantly greater with octreotide LAR 10, 20 or 30 mg every 28 days than with lanreotide SR 30 mg every 7-14 days in a large (n = 125) sequential, 6-month study, but was not significantly different between treatment groups in a small, randomised, nonblind, parallel group study of previously untreated patients. The volume of pituitary tumour shrinkage achieved with octreotide LAR or lanreotide SR was also similar ( approximate, equals 33% after 24 months). Acromegaly symptoms, such as headache, increased perspiration, paraesthesia, fatigue and osteoarthralgia were improved during treatment with octreotide LAR or lanreotide SR. Overall, octreotide LAR is generally well tolerated by most patients. The incidence of gastrointestinal symptoms is about 30% but, in most cases, events are transient and mild to moderate. Gallbladder abnormalities (sediment, sludge, microlithiasis and gallstones) can occur, but only 1% have become symptomatic to date. The prevalence of biliary abnormalities did not change after switching from subcutaneous octreotide, or from lanreotide SR, to octreotide LAR. Glucose metabolism can be affected by octreotide LAR in some patients; about 15% become hyperglycaemic, usually mild in severity. In summary, octreotide LAR controls GH and IGF-1 secretion in about 55-70% of patients with acromegaly. Octreotide LAR is administered intramuscularly every 28 days, offering improved patient compliance and convenience over three-times-daily subcutaneous octreotide. Long-term therapy provides progressive control of serum GH and IGF-1 levels, and is generally well tolerated by most patients. Thus, for the medical management of acromegaly, octreotide LAR is an effective, well tolerated and convenient treatment option.
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PMID:Octreotide long-acting release (LAR): a review of its use in the management of acromegaly. 1460 59

Fibromyalgia (FM) is a common and complex condition, defined as long lasting, widespread musculoskeletal pain, in the presence of tender points (TPs) at specific anatomical sites. Dysautonomic and functional symptoms, such as orthostatic hypotension, tachycardia, effort intolerance, marked fatigue, sleep disorders, cognitive disturbances, psychological distress, paresthesias, headache, genitourinary manifestations, irritable bowel syndrome and bladder dyskinesia, frequently occur. The etiopathogenesis of FM is presently unknown, but nociceptor, autonomic and neuro-endocrine system dysfunctions have been found in patients. Since specific serological or instrumental markers of the syndrome are not yet identifiable, TP search is the only useful diagnostic hallmark. The development of an effective therapy of FM has hitherto been hampered by the incomplete knowledge of its pathogenic mechanisms. In this paper, the most recent information on FM is reviewed.
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PMID:Fibromyalgia: state of the art. 1504 25

Migraine is one of the leading causes of disability. Topiramate has multiple mechanisms and may reduce neurotransmission through the trigeminocervical complex to prevent migraine. In clinical trials for the prevention of migraine, the mean monthly migraine frequency decreased from 5.6 to 4.5 in the placebo group and larger decreases were observed with topiramate (100 mg/day, 5.8 to 3.5; 200 mg/day, 5.1 to 3.0). However, topiramate use is associated with a high incidence of adverse events (paraesthesia, fatigue, anorexia, diarrhoea), which may limit the willingness of patients to use topiramate for the prevention of migraine. BIBN 4096 BS is a non-peptide calcitonin gene-related peptide-receptor antagonist that has recently been trialled in migraine attacks. The primary efficacy end point was the reduction of severe or moderate headache prior to treatment to mild or no headache at 2 h. This endpoint was achieved in 21 of 32 (66%) patients with BIBN 4096 BS 2.5 mg, compared to 27% of patients given placebo. Although BIBN 4096 BS is a non-peptide, it is still administered intravenously, which will probably limit its use to medical centres.
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PMID:New drugs for the prevention and treatment of migraine: topiramate and BIBN 4096 BS. 1501 83

BIBN 4096 BS ([R-(R*,S*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide) is the first selective, highly potent, small molecule, nonpeptide calcitonin gene-related peptide (CGRP) receptor antagonist, which has been developed for the treatment of acute migraine. The objective of this study was to obtain information on the safety, tolerability and pharmacokinetics of BIBN 4096 BS following single intravenous administration of rising doses (0.1, 0.25, 0.5, 1, 2.5, 5 and 10 mg) in 55 healthy male and female volunteers. The study was of single-centre, double-blind (within dose levels), placebo-controlled, randomized, single rising dose design. Blood pressure, pulse rate, respiratory rate, ECG, laboratory tests and forearm blood flow did not reveal any clinically relevant, drug-induced changes. Sixteen adverse events (AEs) were reported by eight of 41 volunteers after BIBN 4096 BS compared to five AEs reported by four of 14 volunteers after placebo. Approximately two-thirds of all AEs related to active treatment occurred at the highest dose of 10 mg. At this dose level, all AEs were confined to the three BIBN 4096 BS-treated females, and consisted mainly of transient and mild paresthesias. Paresthesias were the single most frequent AE, whereas fatigue was the AE which occurred in the highest number of subjects. Only two AEs were of moderate intensity, all remaining AEs were of mild intensity. No serious AEs were reported. The local tolerability after intravenous administration was good. In summary, intravenously administered BIBN 4096 BS revealed a very favourable safety profile over the dose range tested in both genders. Generally well tolerated at all dose levels, it was of satisfactory tolerability in female subjects at the highest dose of 10 mg. The plasma concentration-time courses of BIBN 4096 BS showed multicompartmental disposition characteristics. Mean maximum concentration (Cmax) values appeared to be dose-proportional. Based on the results from the two high dose levels (5 and 10 mg) with sufficient individual subject data, BIBN 4096 BS exhibited a total plasma clearance (CL) of approximately 12 l/h and an apparent volume of distribution at steady state (Vss) of approximately 20 l, resulting in a terminal half-life (t1/2) of approximately 2.5 h. Inter-individual variability was moderate with a coefficient of variation of approximately 45% based on the area under the plasma concentration-time curve (AUC) values. The mean renal clearance (CLR) was approximately 2 l/h, suggesting that renal excretion plays only a minor role in the elimination of unchanged BIBN 4096 BS.
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PMID:Safety, tolerability and pharmacokinetics of BIBN 4096 BS, the first selective small molecule calcitonin gene-related peptide receptor antagonist, following single intravenous administration in healthy volunteers. 1526 53

Fibromyalgia is a frequent disorder of the middle aged, particularly in women characterized by diffuse and widespread pain, and tenderness on palpation at characteristic sites, called tender points. Additional characteristic symptoms of fibromyalgia are fatigue, sleep disturbances, irritable bowel and bladder syndrome, chronic headaches, paresthesia, hearing and vestibular dysfunction. The etiology remains poorly understood. Diagnosis is based on characteristic symptoms, presence of tender points and exclusion of similar confounding conditions. Because of the unknown etiology, all therapies are symptomatic. Interdisciplinary combined treatments can relief the pain in about 50% of the patients.
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PMID:[Fibromyalgia]. 1530 16

Frovatriptan succinate is one of the most recent serotonin receptor agonists to receive FDA, approved labelling for use in the acute management of migraine with or without aura in adults. The mechanism of action of frovatriptan is thought to be similar to that of a serotonin agonist. However, frovatriptan has distinctive pharmacokinetic and pharmacologic properties, chiefly, a high affinity for serotonin receptors 1B and 1D and a long elimination half-life; frovatriptan was shown to be more selective for cerebral than coronary arteries, a property which makes frovatriptan more favourable in patients at risk of coronary artery disease. Additionally, frovatriptan has a half-life of approximately 25 h, substantially longer than that of any other agent within its class. This property makes frovatriptan suitable for patients who typically suffer migraines of long duration and/or those who suffer migraine recurrence. The efficacy of frovatriptan in the treatment of acute migraine was demonstrated in five double-blind, randomised, placebo-controlled trials. At 2h, headache response rates for frovatriptan 2.5 mg ranged from 38 to 40% compared to 22-35% for placebo. Headache recurrence for frovatriptan 2.5 mg at 24h ranged from 9 to 14% compared with 18% in placebo subjects. Frovatriptan has no clinically significant pharmacokinetic interactions with drugs used for migraine prophylaxis or with commonly prescribed medications. Adverse effects of frovatriptan including dizziness, paresthesia, dry mouth, fatigue and flushing were generally mild and well tolerated. Given the fact that patient response to serotonin agonists is individualised, and selecting an effective agent may involve trial and error, frovatriptan is a welcome alternative in the acute management of migraine.
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PMID:Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. 1531 27

The aim of this study was to assess the prevalence of Antimicrosomal Antibodies AMA, thyroid function and the occurrence of hypothyroidism symptoms in patients with Multiple Sclerosis (MS). Clinical examination was carried out in 21 MS patients; thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 and AMA were measured. Mean age was 41.05 years. Hypothyroidism symptoms included fatigue, weakness, lethargy and paresthesia. AMA were found in four patients (19%). Three categories of disease duration were considered: <60 months (3 patients AMA+; 7 AMA-), 60-120 months (8 patients AMA-), and >120 months (1 patient AMA+; 2 AMA-). Two patients presented decreased free T4 levels, but there was no associated decrease in T4 and TSH levels. In two patients, a mild increase in TSH levels was observed: one presented normal T4 levels (subclinical hypothyroidism) and the other one had low free T4 levels (classical hypothyroidism). We conclude that AMA measurement and thyroid function tests should become part of the routine assessment of MS patients, in view of the inaccuracy currently observed in the assessment of clinical hypothyroidism as a result of the superposition of hypothyroidism and MS signs and symptoms.
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PMID:[Prevalence of antimicrosomal antibodies in patients with multiple sclerosis]. 1533 29


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