Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new mysoline research articles will be listed here shortly after becoming available to us.
Medical research on mysoline
How are we doing with the treatment of essential tremor (ET)?
Eur J Neurol. 2010 Jan 7;
Louis ED, Rios E, Henchcliffe C
Background: The pharmacological treatment of essential tremor (ET) is not optimal. There are only two first-line medications and troublesome side effects are common. It is not uncommon for patients to simply stop taking medication. Yet, no published data substantiate or quantify this anecdotal impression. Objectives: To determine, amongst patients with ET who were prescribed medication for tremor, what proportion are still taking medication and what proportion have stopped? Methods: Five hundred and twenty-eight patients with ET from three distinct study settings (clinical, brain donors, population) were interviewed. Results: A clear pattern that emerged across settings was that the proportion of patients with ET who had stopped medication was sizable and consistently similar (nearly one-third): 31.4% (clinical), 24.3% (brain donors), 30.0% (population), 29.8% (overall). A similarly high proportion of cases with severe tremor had stopped their medication: 31.9% (clinical), 36.4% (brain donors). For the four most commonly used medications (propranolol, primidone, diazepam, topiramate), one-half or more of the treated patients had stopped the medication; amongst the less commonly used medications, the proportion who stopped was even higher. Conclusions: Nearly one of every three patients with ET who had been prescribed medication for tremor had discontinued pharmacotherapy. Even more revealing was that a similar proportion of cases with severe tremor had stopped medication. These data make tangibly evident that there is a sizable population of patients with ET who are untreated and disabled, and underscore the inadequacy of current pharmacotherapeutic options for this common neurological disease.
J Chromatogr A. 2010 Jan 22; 1217(4): 558-64
Bisceglia KJ, Yu JT, Coelhan M, Bouwer EJ, Roberts AL
The presence of pharmaceuticals and other wastewater-derived micropollutants in surface and groundwaters is receiving intense public and scientific attention. Yet simple GC/MS methods that would enable measurement of a wide range of such compounds are scarce. This paper describes a GC/MS method for the simultaneous determination of 13 pharmaceuticals (acetaminophen, albuterol, allopurinol, amitriptyline, brompheniramine, carbamazepine, carisoprodol, ciclopirox, diazepam, fenofibrate, metoprolol, primidone, and terbinafine) and 5 wastewater-derived contaminants (caffeine, diethyltoluamide, n-butylbenzene sulfonamide, n-nonylphenol, and n-octylphenol) by solid phase extraction (SPE) and derivatization with BSTFA. The method was applied to the analysis of raw and treated sewage samples obtained from a wastewater treatment plant located in the mid-Atlantic United States. All analytes were detected in untreated sewage, and 14 of the 18 analytes were detected in treated sewage.
[Anticonvulsants as bioantioxidants under stress conditions]
Biomed Khim. 2009 Jul-Aug; 55(4): 519-24
Bogdanov GN, Mishchenko DV, Kotel'nikova RA, Frog ES, Faĭngol'd II, Tat'ianenko LV, Dorokhotova OV, Nartsissov IaR
The action of heterocyclic amides series (ethosuximide, phenytoin, primidone) on lipid peroxidation and membrane bound monoamine oxidases A and B under stress condition has been studied. The intraperitoneal injection of the drugs resulted in enhancement of SOD, decrease of brain malondialdehyde content and mitochondrial activity of monoamine oxidases A and B.
Evaluation of UV/H(2)O(2) treatment for the oxidation of pharmaceuticals in wastewater.
Water Res. 2010 Mar; 44(5): 1440-8
Rosario-Ortiz FL, Wert EC, Snyder SA
Advanced oxidation treatment using low pressure UV light coupled with hydrogen peroxide (UV/H(2)O(2)) was evaluated for the oxidation of six pharmaceuticals in three wastewater effluents. The removal of these six pharmaceuticals (meprobamate, carbamazepine, dilantin, atenolol, primidone and trimethoprim) varied between no observed removal and >90%. The role of the water quality (i.e., alkalinity, nitrite, and specifically effluent organic matter (EfOM)) on hydroxyl radical (OH) exposure was evaluated and used to explain the differences in pharmaceutical removal between the three wastewaters. Results indicated that the efficacy of UV/H(2)O(2) treatment for the removal of pharmaceuticals from wastewater was a function of not only the concentration of EfOM but also its inherent reactivity towards OH. The removal of pharmaceuticals also correlated with reductions in ultraviolet absorbance at 254nm (UV(254)), which offers utilities a surrogate to assess pharmaceutical removal efficiency during UV/H(2)O(2) treatment.
Ther Drug Monit. 2010 Feb; 32(1): 102-6
Heideloff C, Bunch DR, Wang S
Therapeutic drug monitoring of antiepileptic drugs (AEDs) is important in maximizing the therapeutic response while minimizing the adverse effects. High-performance liquid chromatography (HPLC) is the most commonly used technique for this purpose. Recently, commercial monolithic columns were introduced, which consist of a single rod of fused silica or polymer. The objective of this work was to develop a simple and fast method to quantify 10 commonly measured AEDs or metabolites [carbamazepine, carbamazepine-10,11-epoxide, felbamate, lamotrigine, 10,11-dihydro-10-hydroxy-carbamazepine (active metabolite of oxcarbazepine), pentobarbital, phenobarbital, phenytoin, primidone, and zonisamide] in serum/plasma by HPLC using a reverse-phase monolithic column. Serum/heparin plasma (100 microL) was mixed with an internal standard solution (5-ethyl-5-p-tolylbarbituric acid in methanol, 250 microL). After centrifugation at 15,500 g for 10 minutes, 15 microL of supernatant was injected into a monolithic column. The analytes were eluted with an isocratic solution of 0.1 M, pH 6.5, phosphate buffer:methanol:acetonitrile (77:20:3), monitored at 210 nm. The chromatography time was 16 minutes. The method was linear from 0.4-4.9 to 21.2-190.9 microg/mL depending on the analytes with analytical recovery of 80%-114%. The inter- and intra-assay coefficients of variation were 100 therapeutic drugs and common endogenous substances were tested and showed no interference. Comparison studies for 6 AEDs or metabolites were performed against commercial HPLC methods. Three AEDs were compared with Food and Drug Administration-approved immunoassays. All comparisons had R > 0.96 with slope ranging from 0.86 to 1.20. This is a simple and fast HPLC method suitable for measuring the 10 AEDs or metabolites. The use of the monolithic column resulted in increased sensitivity, better resolution, and a shorter analytical time compared with a regular C18 column.
Psychiatr Serv. 2009 Nov; 60(11): 1439-45
Gaynes BN, Warden D, Trivedi MH, Wisniewski SR, Fava M, Rush AJ
The authors provide an overview of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a large-scale practical clinical trial to determine which of several treatments are the most effective "next-steps" for patients with major depressive disorder whose symptoms do not remit or who cannot tolerate an initial treatment and, if needed, ensuing treatments. Entry criteria were broadly defined and inclusive, and patients were enrolled from psychiatric and primary care clinics. All participants began on citalopram and were managed by clinic physicians, who followed an algorithm-guided acute-phase treatment through five visits over 12 weeks. At the end of each sequence, patients whose depression had not fully remitted were eligible for subsequent randomized trials in a sequence of up to three clinical trials. In general, remission rates in the study clinics were lower than expected, suggesting the need for several steps to achieve remission for most patients. There was no clear medication "winner" for patients whose depression did not remit after one or more aggressive medication trials. Both switching and augmenting appeared to be reasonable options when an initial antidepressant treatment failed, although these two strategies could not be directly compared. Further, the likelihood of remission after two vigorous medication trials substantially decreased, and remission would likely require more complicated medication regimens for which the existing evidence base is quite thin. STAR*D demonstrated that inclusion of more real-world patients in clinical trials is both feasible and informative. Policy implications of the findings, as well as the study's limitations, are discussed.
Pediatr Dermatol. 2009 Sep-Oct; 26(5): 536-46
Newell BD, Moinfar M, Mancini AJ, Nopper AJ
OBJECTIVE: To review 32 pediatric patients with anticonvulsant hypersensitivity syndrome. DESIGN: Retrospectively, data and photographs were collected on 32 patients who had been diagnosed with anticonvulsant hypersensitivity syndrome. SETTING: The sections of dermatology at Children's Memorial Hospital in Chicago, Illinois, and Children's Mercy Hospitals and Clinics in Kansas City, Missouri. MAIN OUTCOME MEASURES: Presentation, implicated medications, laboratory evaluations, complications, treatment and outcome. RESULTS: The mean age of all patients with anticonvulsant hypersensitivity syndrome (ACHSS) was 8.9 years. The mean duration of anticonvulsant therapy before onset of symptoms was 3 weeks. Phenytoin, carbamazepine, and phenobarbital were the most commonly implicated medications. Lamotrigine, oxcarbamazepine, and primidone were implicated in some of our patients. Fever and rash were seen in all patients, while lymphadenopathy was found in 84.4% of patients. Hematologic abnormalities were seen in 93.8% and hepatic involvement was seen in 90.4% of cases, representing the two most commonly involved systems. Atypical lymphocytosis and eosinophilia was seen in 72% and 56% of patients, respectively. Renal and pulmonary involvement were each seen in 15.6% of cases. Systemic steroids were used in 59.4% of ACHSS patients; 16% of patients received intravenous immunoglobulin. No deaths were reported in our group of pediatric patients. CONCLUSIONS: The ACHSS is a distinct clinical entity which may occur in pediatric patients treated with anticonvulsants, and may have potentially life-threatening consequences. Involvement of multiple organ systems, including the hematologic, hepatic, renal, and pulmonary systems was common. Treatment varied widely, but ranged from supportive care to systemic corticosteroids.
[Barbiturate rheumatism as a complication of essential tremor]
Rev Neurol. 2009 Sep 16-30; 49(6): 332-3
Venegas-Francke P, Sinning M
Environ Toxicol Chem. 2009 Dec; 28(12): 2528-36
Kahle M, Buerge IJ, Müller MD, Poiger T
Hydrophilic, persistent markers are useful to detect, locate, and quantify contamination of natural waters with domestic wastewater. The present study focused on occurrence and fate of seven marker candidates including carbamazepine (CBZ), 10,11-dihydro-10,11-dihydroxycarbamazepine (DiOH-CBZ), primidone (PMD), crotamiton (CTMT), N-acetyl-4-aminoantipyrine (AAA), N-formyl-4-aminoantipyrine (FAA), and benzotriazole (BTri) in wastewater treatment plants (WWTPs), lakes, and groundwater. In WWTPs, concentrations from 0.14 microg/L to several micrograms per liter were observed for all substances, except CTMT, which was detected at lower concentrations. Loads determined in untreated and treated wastewater indicated that removal of the potential markers in WWTPs is negligible; only BTri was partly eliminated (average 33%). In lakes, five compounds, CBZ, DiOH-CBZ, FAA, AAA, and BTri, were consistently detected in concentrations of 2 to 70 ng/L, 3 to 150 ng/L, less than the limit of quantification to 30 ng/L, 2 to 80 ng/L, and 11 to 920 ng/L, respectively. Mean per capita loads in the outflows of the lakes suggested possible dissipation in surface waters, especially of AAA and FAA. Nevertheless, concentrations of CBZ, DiOH-CBZ, and BTri correlated with the actual anthropogenic burden of the lakes by domestic wastewater, indicating that these compounds are suitable for quantification of wastewater contamination in lakes. Marker candidates were also detected in a number of groundwater samples. Carbamazepine concentrations up to 42 ng/L were observed in aquifers with significant infiltration of river water, receiving considerable wastewater discharges from WWTPs. Concentration ratios between compounds indicated some elimination of BTri and DiOH-CBZ during subsurface passage or in groundwater, while CBZ and PMD appeared to be more stable and thus are promising wastewater markers for groundwater. The wastewater burden in groundwater, estimated with the markers CBZ and PMD, reached up to 6%.
Environ Sci Technol. 2009 Jul 1; 43(13): 4858-63
Wert EC, Rosario-Ortiz FL, Snyder SA
The reduction of ultraviolet (UV) absorbance at 254 nm (UV254) and true color were identified as appropriate surrogates to assess the oxidation of six pharmaceuticals (i.e., carbamazepine, meprobamate, dilantin, primidone, atenolol, and iopromide) during ozonation of wastewater. Three tertiary-treated wastewaters were evaluated during oxidation with ozone (O3) and O3 coupled with hydrogen peroxide (O3/H2O2). The correlation between pharmaceutical oxidation and removal of UV254 was dependent upon the reactivity of each specific compound toward ozone, as measured by the second-order rate constant (k'(O3)). Oxidation of compounds with k'(O3) > 10(3) M(-1) s(-1) correlated well (R2 > 0.73) with UV254 reduction between 0-50%. Oxidation of compounds with apparent k'(O3) < 10 M(-1) s(-1) resulted primarily from hydroxyl radicals and correlated well (R2 > 0.80) with the UV254 reduction of 15-85%. The removal of true color also correlated well (R2 > 0.85) with the oxidation of pharmaceuticals during the ozonation of two wastewaters. These correlations demonstrate that UV254 reduction and true color removal may be used as surrogates to evaluate pharmaceutical oxidation in the presence or absence of dissolved ozone residual during advanced wastewater treatment with O3 or O3/H2O2. The use of online UV254 measurements would allow wastewater utilities to optimize the ozone dose required to meet their specific treatment objectives.