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)

Classic renal tubular acidosis is characterized by a primary defect in establishment of a large hydrogen ion gradient across the distal renal tubule. Thus the development of hyperchlorenic metabolic acidosis follows. In addition, hypokalemia results from renal potassium wasting secondary hyperaldosteronism from sodium wasting and contraction of the extracellular fluid. The presenting signs and symptoms are growth retardation, fatigue, periodic paralysis, polyuria, polydipsia, vomiting and constipation as well as nephrocalcinosis and nephrolithiasis. It is suggested that effective treatment with alkali therapy requires markedly higher doses than formerly recommended, and may related to a higher rate of endogenous acid production from (1) intermediary metabolism of sulfur amino acids and organic acids, (2) impaired tubular reabsorption of bicarbonate and (3) hydrogen ion release from hydroxyapatite formation. It is also suggested that acidosis may interfere with vitamin D metabolism and thus play an important role in the pathoetiology of the growth failure in children with this disorder.
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PMID:Acid-base, calcium, potassium and aldosterone metabolism in renal tubular acidosis. 3 60

The major symptoms presented by the elderly patient with primary hyperparathyroidism (HPT) were studied in 30 patients, all of whom were over 70 years of age (70-89). Neuromuscular symptoms, fatigue or mental symptoms were the main complaint in 14 patients. Nephrolithiasis, pancreatitis, skeletal changes or thyroid diseases were associated with HPT in 13 patients. Three patients were considered to be asymptomatic. Seven out of the eight patients with neuromuscular symptoms, and two of the three patients with extreme fatigue as the dominant symptom, improved postoperatively. This study indicates that for elderly patients with HPT especially when associated with neuromuscular symptoms or fatigue, surgical therapy is the treatment of choice.
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PMID:Indications for surgery in the elderly patient with primary hyperparathyroidism. 102 May 88

Several recent articles question whether patients with asymptomatic hyperparathyroidism and minimal hypercalcemia should be treated by parathyroidectomy. We therefore reviewed our experience in 103 consecutive patients with primary hyperparathyroidism who were treated by parathyroidectomy to determine, first, how many of these patients had asymptomatic or symptomatic hyperparathyroidism, and second, did these patients benefit from parathyroidectomy? We also analyzed the safety of parathyroidectomy in 426 consecutive patients, including 79 who required reoperation for hyperparathyroidism, specifically looking for complications and the outcome of these procedures. Our study documents the following: (1) only 2 of 103 (2%) patients referred for parathyroidectomy had "true" asymptomatic hyperparathyroidism; (2) only symptoms of fatigue, bone pain, and weight loss correlated with the degree of hypercalcemia, whereas muscular weakness, psychiatric symptoms, nocturia, polyuria, recent memory loss, constipation, and nephrolithiasis did not; (3) only 1 of 15 patients who were referred as asymptomatic were truly asymptomatic after more thorough questioning, and all 14 improved following parathyroidectomy; (4) 81% of the patients who were referred with symptoms improved following parathyroidectomy; and (5) permanent complications occurred in only 4 patients. All but 1 had reoperations for persistent or recurrent hyperparathyroidism (3 vocal cord paralyses and 1 hypoparathyroidism requiring autotransplantation of cryopreserved parathyroid tissue). There was 1 death of an 84-year-old woman with hypercalcemic crisis. Thus, most patients with hyperparathyroidism are symptomatic and benefit symptomatically and metabolically from parathyroidectomy, which is a safe operation.
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PMID:Diagnosis and management of asymptomatic hyperparathyroidism: safety, efficacy, and deficiencies in our knowledge. 176 65

Topiramate is a recently licensed and marketed antiepileptic drug in the UK for use as add-on therapy for refractory partial epilepsy. It has multiple modes of action involving voltage-dependent sodium channels, GABA receptors and glutamate receptors. Topiramate has very favourable pharmacokinetics as it is primarily excreted unchanged. Its metabolism is, however, increased by enzyme inducers, and it can inhibit the metabolism of phenytoin in some patients. Its efficacy as adjunctive treatment in refractory partial epilepsy in adults appears good, over 40% of patients have a 50% or greater reduction in seizure frequency when topiramate is added to their regime with up to 7% becoming seizure free. The main adverse events are ataxia, impaired concentration, confusion, dizziness, fatigue, parasthesia, somnolence and "thinking abnormal'. Most of these occurred during rapid titration. During long-term treatment, weight loss also occurred and nephrolithiasis occurred in 1.5% of patients receiving topiramate. Topiramate is a useful and well-tolerated addition to our treatment of refractory epilepsy, but it should be titrated slowly in order to avoid adverse events.
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PMID:Topiramate: a new antiepileptic drug for refractory epilepsy. 890 21

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

Although the incidence of hyperparathyroidism (HPT) in the elderly exceeds 1.5%, limited resources and co-morbidity inhibit referral for parathyroidectomy. To determine the risks and benefits of surgery, we examined the outcomes of elderly patients who underwent exploration for primary HPT. Data from 211 consecutive patients who underwent parathyroidectomy by one surgeon at the Johns Hopkins Hospital between August 1990 and May 1996 were recorded prospectively. Of these patients, 184 had primary HPT. Demographic and outcome data of elderly patients (> 70 years of age) (n = 36) were compared to those from younger patients (< 70 years of age) (n = 148). Preoperative symptoms of mental impairment, bone disease, and fatigue were more common in elderly patients (p < 0.05), and nephrolithiasis was more frequent in younger patients (p < 0.025). Elderly patients presented with more advanced disease, manifested by higher preoperative parathyroid hormone levels (301.9 +/- 63.3 vs. 169.2 +/- 14.3 pg/ml, p < 0.05). The cure rate (94.4%), morbidity (5.5%), and mortality (0%) in the elderly were indistinguishable from those of their younger cohorts (98%, 1.4%, and 0%, respectively). In conclusion, the more advanced disease seen in the elderly suggests that they are referred for surgery with a higher threshold than younger patients. Although several series of parathyroidectomy in elderly patients have reported high morbidity rates, significant mortality, and long length of stay (LOS), we found that parathyroidectomy in these patients can be performed with high cures, low morbidity, no mortality, short LOS, and high patient satisfaction. These data suggest that the benefits of surgery outweigh its risks and argue for a lower threshold for referral of elderly patients with primary HPT for surgical treatment.
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PMID:Parathyroidectomy in the elderly: do the benefits outweigh the risks? 959 24

Six studies are cited to demonstrate that topiramate is effective as adjunctive therapy for refractory partial-onset seizures in adults. Subsequent studies indicate that topiramate is also effective as monotherapy in adults and as adjunctive therapy for partial-onset seizures in children, tonic-clonic seizures of nonfocal origin in children and adults, and drop attacks in Lennox-Gastaut syndrome. Adverse effects for adults and children included dizziness, fatigue, ataxia, confusion, somnolence, nephrolithiasis, paresthesia, and weight loss. More adverse effects were observed at higher doses. Topiramate exhibits rapid absorption, long duration of action, and minimal interaction with other antiepileptic drugs.
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PMID:Topiramate. 1053 Jun 97

Indinavir is a protease inhibitor used in the treatment of patients with HIV infection. Combination antiretroviral therapy with indinavir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is associated with greater reductions in viral load, greater increases in CD4+ cell counts, and reduced morbidity and mortality when compared with 2 NRTIs alone. In the landmark clinical trial ACTG 320, the rate of progression to AIDS or death (primary end-point) among zidovudine-experienced patients treated with indinavir, zidovudine and lamivudine was approximately half that of patients who received only zidovudine plus lamivudine (6 vs 11%; p < 0.001). The durability of an indinavir-containing regimen was demonstrated in Merck protocol 035, an ongoing trial in which a significant proportion of patients had sustained viral suppression for up to 3 years. Merck protocol 039, also an ongoing trial, showed a greater effect on surrogate markers of HIV disease progression with indinavir-based triple therapy than with zidovudine plus lamivudine or indinavir monotherapy in patients with advanced disease (median baseline CD4+ count 15 cells/microL). Numerous additional clinical trials have established the beneficial antiviral and immunological effects of indinavir in both antiretroviral-naive and -experienced patients with HIV infection. Indinavir is associated with various drug class-related adverse events, including gastrointestinal disturbances (e.g. nausea, diarrhoea), headache and asthenia/fatigue. A lipodystrophy syndrome has been commonly reported with indinavir and other protease inhibitors combined with NRTIs, but it has also been reported in many protease inhibitor-naive patients, and a definitive causal link has not been established between the syndrome and protease inhibitors. Nephrolithiasis may develop in about 9% of patients receiving indinavir but does not appear to be associated with other protease inhibitors; <0.5% of patients receiving indinavir discontinue the drug because of nephrolithiasis, which may be the extreme end of a continuum of crystal-related renal syndromes. Additional renal problems (e.g. nephropathy) have been reported in small numbers of patients receiving indinavir. In summary, indinavir is a protease inhibitor with well documented efficacy when used as part of combined therapy in patients with HIV infection. Both US and UK treatment guidelines continue to recommend protease inhibitor-based regimens including indinavir as a first-line option. Indinavir is being studied as a twice daily and once daily regimen with a low dosage of ritonavir as a way to alleviate tolerability, drug interaction and patient compliance/adherence issues. Indinavir-containing triple therapy has demonstrated positive effects not only on surrogate markers of disease progression, but also on clinical end-points of mortality and morbidity in patients with HIV disease. Protease inhibitors are a significant advance in the care of patients with HIV infection, and, in an era of evidence-based medicine, indinavir represents an important component of antiretroviral treatment strategies.
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PMID:Indinavir: a review of its use in the management of HIV infection. 1065 94

We present case report of primary hyperparathyroidism treated surgically as well as a review of literature concerning this subject. The disease of not well known etiology presents with elevated parathormon levels and hypercalcemia. Primary hyperparathyroidism which states 85% percent of all kinds of hyperparathyroidism is usually parathyroid adenoma, in 11-15% glandular hyperplasia and in 1-4% parathyroid cancer. Clinical symptoms are muscle weakness and fatigue, nephrolithiasis, occasionally peptic ulcers, pancreatitis, hypertension. Laboratory test reveal increased level of PTH, hypercalcemia, elevated alkaline phosphatase levels and decreased phosphorus levels. Diagnostic imaging techniques such as ultrasonography, MRI or CT have sensitivity about 52-75%. Highest sensitivity in localization of ectopic parathyroid adenoma has sestamibi scintigraphy with technetium-99. Skeleton x-rays show typical changes in distal parts of bones and osteopenia. Treatment of choice is surgical excision of adenoma. Normalization of PTH and calcium levels after surgery and improvement of renal, musculoskeletal and circulatory system function could be achieved in 95%. Most common complications are recurrent laryngeal nerve injury, hypo- or hyperparathyroidism, bleeding or stridor.
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PMID:[Primary hyperparathyroidism--case report and review of the literature]. 1682 51

Primary hyperparathyroidism (PHPT) is classically thought of as the somatic manifestation of hypercalcemia in which patients suffer from a variety of complaints including abdominal pain, nephrolithiasis, osteopenia, and mental status changes. Contemporary PHPT patients are generally free of somatic manifestations and are most often diagnosed when routine biochemical testing shows an elevated serum calcium level. The modern day patient may present with much more subtle neurocognitive symptoms including fatigue, lethargy, muscle weakness, depression, and cognitive impairment. Advances in imaging technology, intraoperative parathyroid hormone measurement, and surgical technique now allow parathyroidectomy to be performed using a focused approach without the absolute need of a four-gland exploration. Minimally invasive techniques allow the procedure to be accomplished under local anesthesia on an outpatient basis. This brief review summarizes the presentation, biochemical evaluation, operative intervention, and follow-up care of the modern day PHPT patient.
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PMID:Primary hyperparathyroidism. 1760 56


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