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We describe a case of a patient with glossopharyngeal neuralgia (refractory to treatment with carbamazepine, amytriptyline, diazepam, and indomethacin) treated with lamotrigine as monotherapy, the first described, who responded completely to the therapy and did not complain of side effects. The complete analgesic effect was reached at the lamotrigine daily dose of 200 mg per day and was maintained at that dose for additional 6 months, with the blood concentration within the reference range.
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Phenytoin (5,5-diphenylhydantoin), which has been in use for 60 years, is still an important antiepileptic drug. Its primary mechanism of action is modulation of the sustained repetitive firing of neurones by direct inhibition and blockage of voltage-gated sodium channels in the neuronal cell membrane, and by delay of cellular reactivation. The plasma protein binding of phenytoin is normally between 90% and 95%. The drug is rapidly distributed from the blood to the tissues and is almost completely metabolized in the liver. The plasma phenytoin concentration normally reaches the steady-state level within 1-2 weeks. The half-life of phenytoin is less than 20 h in low doses, but is prolonged in high doses, newborn infants and elderly people. The half-life is shortened when phenytoin is given concomitantly with an enzyme-inducing drug, such as phenobarbital or carbamazepine. Phenytoin is effective for treating generalized tonic-clonic seizures, partial seizures with or without generalization, and convulsive status epilepticus. Over the years, many new, and even serious, adverse effects of phenytoin have been recognized. Phenytoin encephalopathy, manifesting as cognitive impairment and a cerebellar syndrome, is an important adverse neurological effect, the development of which depends on the saturation kinetics of phenytoin, individual differences in phenytoin metabolism, an inhibitory effect of certain drugs on phenytoin metabolism, or the ability of certain drugs to displace phenytoin from plasma proteins, leading to an increase in the plasma level of unbound phenytoin. Because of its potentially adverse effects, phenytoin is not recommended as the first choice for treating epileptic seizures, except as a co-drug for managing convulsive status epilepticus. In patients with epilepsy who also have intellectual disability, and are susceptible to balance disturbances and cognitive dysfunction, it is wise to replace phenytoin with another drug, such as carbamazepine or oxcarbazepine. The long-term use of phenytoin is not recommended for patients with loss of locomotion, marked cognitive impairment, or symptoms and signs of cerebellar disease. The prevention of phenytoin intoxication, with the subsequent development of phenytoin-induced encephalopathy, depends on careful observation of the patients and frequent monitoring of plasma levels of phenytoin and other concomitantly administered antiepileptic drugs.
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Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning.
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Psychiatric drugs influence DNA methylation patterns over and above cell type composition in bipolar disorder. Drug-related changes in DNA methylation are therefore not only an important confounder in psychiatric epigenetics but may also inform on the biological mechanisms underlying drug efficacy.
Serum total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and very low-density lipoprotein cholesterol, triglyceride, apolipoproteins A1 and B levels were studied in 57 healthy children and in 39 children with epilepsy who had been receiving carbamazepine (CBZ) (23 children) for 1.58 +/- 1.10 years or valproic acid (VPA) (16 children) for 1.34 +/- 1.11 years. In patients receiving CBZ, mean TC level, mean LDL-C level, mean TC/HDL-C ratio and mean LDL-C/HDL-C ratio-were significantly higher than controls. None of the mean levels of serum lipids evaluated in patients receiving VPA was significantly different from the corresponding control group mean. Changes in serum lipids correlated with neither duration of therapy or plasma antiepileptic levels nor age or gender.
The authors recommend that additional studies regarding the relationship between the growth of prolactinoma and atypical antipsychotics would be worthwhile.
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This report involves a patient suffering from focal epilepsy caused by an unruptured, intracranial aneurysm (UIA), and her treatment using intravascular embolisation, with an excellent postoperative outcome in terms of the epilepsy. A 52 year-old, right-handed woman had been suffering for three years from focal seizures, characterized by loss of consciousness, and oroalimentary and hand automatisms. The epilepsy was not controlled by carbamazepine monotherapy. Magnetic resonance imaging and digital subtraction angiography revealed a saccular aneurysm at the bifurcation of the middle cerebral artery, in contact with the cortex of the temporal opercular region. An intra-arterial embolisation, using a detachable, mechanical spiral (MDS, Bold Platinum), was performed, with no complications. The purpose of embolisation was the treatment of the aneurysm. The patient had two more, complex partial seizures (CPS) in the early postoperative period, but was seizure-free between September 1998 and September 2002. This is the first case report that presents the successful treatment of UIA-related epilepsy by means of intravascular embolisation.
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The present study investigated the applicability of a laccase based bioprocess for the treatment of a mixture containing 13 selected pharmaceuticals. To do so, laccase was immobilized as cross-linked enzyme aggregates (MAC-CLEAs) on amine functionalized magnetic nanoparticles using chitosan/1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDAC) as the cross-linking system. The activity recovery of laccase reached 61.4% under the optimal conditions of MAC-CLEAs formation. The latter exhibited enhanced storage stability over one year at 4°C and showed better temperature resistance compared to its soluble counterpart. The biocatalysts were properly recycled and the catalytic activity recovery was good even after a hundred and fifty batch reactions. Complete removal of pharmaceuticals like acetaminophen, diclofenac, mefenamic acid, atenolol and epoxy carbamazepine and partial removal of fenofibrate, diazepam, trimethoprim, and ketoprofen by laccase was achieved within 12h of incubation, whereas efficient removal of indometacin required the presence of mediator.
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Twenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL) activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level.
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The purpose of this work was to investigate the mechanisms of cocrystal formation during cogrinding and storage of solid reactants, and to establish the effects of water by cogrinding with hydrated form of reactants and varying RH conditions during storage.
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A prospective Phase II study of CPT-11 in adult patients with recurrent supratentorial glioblastoma multiforme (GBM).
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CBZ affects not only the metabolism of IMI and its metabolites, but also their protein binding. Therefore, despite considerable reductions in total serum levels of IMI and DMI, but when the unchanged free fraction concentration of these compounds is maintained, a dosage elevation of IMI does not seem to be necessary after CBZ addition to TCA therapy.
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The delay in initiating prophylaxis appears to have no influence on prophylaxis outcome. Instead, those whose illness was more severe were treated earlier and these patients subsequently showed a relatively greater response. If severity is not controlled for as part of the analysis, latency may be mistaken as an important predictor for response.
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Effect of adenosinergic agents were investigated in lithium-pilocarpine-induced status epilepticus (SE) in rats. Adenosinergic agents such as adenosine (50, 100 mg/kg), 2-choloroadenosine (1, 2 mg/kg), carbamazepine (20, 80 mg/kg), N6-cyclohexyladenosine (1, 2 mg/kg) and dipyridamole (10, 20 mg/kg) produced theophylline-sensitive protective effects as they dose-dependently prolonged the latencies for onset of forelimb clonus with rearing. Pretreatment with Ro 5-4864 (20 mg/kg i.p.) did not offer any protection. These results indicate the possible involvement of adenosinergic mechanism in preventing lithium-pilocarpine-induced SE and mortality.
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Fifty-one Polish specialists, working in academic or clinical settings, completed the questionnaire. They limited combination therapy to two or three antiepileptic drugs. Valproate was the treatment of choice for myoclonic, generalized tonic-clonic seizures and Lennox-Gastaut syndrome. For infantile spasms caused by tuberous sclerosis and of symptomatic etiology, vigabatrin was treatment of choice; valproate and ACTH were other first line options. Valproate and ethosuximide were chosen for childhood absence epilepsy and valproate for juvenile absence epilepsy. Carbamazepine was the first-line treatment option for benign partial epilepsy of childhood with centrotemporal spikes and complex partial seizures. In the treatment of juvenile myoclonic epilepsy for males valproate, for females lamotrigine were chosen.
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To review the time to withdrawal, remission, and first seizure of carbamazepine compared with phenobarbitone when used as monotherapy in people with partial onset seizures (simple or complex partial and secondarily generalised) or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
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The rheobase of motor and sensory fibres was lower in the control group than the values of patients before and after CBZ and VPA therapy.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening drug reactions considered to be part of the spectrum of a single pathological process.
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During this period, six patients were identified. All had an aggravation of their epilepsy in both clinical and EEG activities. OXC had been used because of an incorrect diagnosis of focal epilepsy or generalized tonic-clonic seizures (GTCSs) of undetermined origin (no syndromic classification of the epilepsy). Before OXC, only one patient had experienced a worsening of seizures with an inadequate drug (CBZ). Four had juvenile myoclonic epilepsy, one had juvenile absence epilepsy, and one had IGE that could not be classified into a precise syndrome. OXC (dosage range, 300-1,200 mg/day) was used in monotherapy in all of them except for one patient. Aggravation consisted of a clear aggravation of myoclonic jerks (five cases) or de novo myoclonic jerks (one case). Three patients had exacerbation of absence seizures. One patient had worsened dramatically and had absence status, and one had de novo absences after OXC treatment. The effects of OXC on GTCSs were less dramatic, with no worsening in frequency in three and a slight increase in three.
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In this study, we used isotopic (delta18O, delta2H, delta34S-SO4) and chemical tracers (boron) to assess the sources and transport processes of the micropollutants carbamazepine, galaxolide, and bisphenol A in groundwater underlying the city of Halle (Saale), Germany. Their ubiquitous presence in urban groundwater results from a combination of local river water infiltration, sewer exfiltration, and urban stormwater recharge. Attenuation during transport with infiltrating river water increased from carbamazepine (0-60%) to galaxolide (60-80%) in accordance with their increasing sorption affinity and decreasing recalcitrance against biodegradation. Distinctly higher attenuation during transport was found for carbamazepine (85-100%) and galaxolide (95-100%) if micropollutants originated from sewer exfiltration. Most likely, this is related to higher contents of organic matter and higher transit times of the respective flow paths. Although attenuation undoubtedly also affects the transport of bisphenol A, quantification is limited due to additional contributions from the urban stormwater recharge. As a consequence, micropollutant loads in groundwater indicate that groundwater discharge may dominate the export of bisphenol A from urban areas.
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The authors investigated the occurrence of pathological gambling among cocaine-dependent outpatients, its influence on short-term outcome of treatment, and comparative characteristics of patients with and without pathological gambling.
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Overall, 45 (84.9%) subjects reported treatment-emergent adverse events (TEAEs); most were mild or moderate in severity. The most commonly reported TEAEs were somnolence (n=14, 26.4%), sedation (n=12, 22.6%), dizziness (n=11, 20.8%), headache (n=9, 17.0%), and nausea (n=7, 13.2%). There were no clinically significant changes in vital signs, including weight. Mean changes in laboratory parameters were small, with values that were within the normal range for the majority of subjects. Few changes relative to screening for other safety parameters occurred. Mean total YMRS score decreased from baseline at each study visit. HAM-D and MADRS scores decreased from baseline at Weeks 4 and 8, and all three CGI-BP components (overall bipolar disorder, mania, and depression) improved during the study.
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Menstrual disorders, reduced fertility and sexual problems seem to be more frequent in women with epilepsy than in the general population. Most investigations concerning menstrual disturbances in epilepsy patients, however, are small and based on selected materials. We therefore wanted to investigate the frequency of menstrual disturbances in a large, unselected population of epilepsy patients.
The binding of carbamazepine to human serum albumin was studied in vitro using solid-phase microextraction (SPME) with liquid chromatography-ultraviolet detection (LC-UV), as well as spectroscopic fluorescence and nuclear magnetic resonance ((1)H NMR) techniques. We were able to recognize one high affinity binding site with both fluorescence and SPME methods. Additionally, SPME experiment showed the existence of one lower affinity binding site for carbamazepine at the range of concentrations studied with fluorescence. The analysis of Hill's plot indicated positive cooperativity between drugs located in these two binding sites. Two low affinity-binding sites have been found with SPME-LC-UV analysis performed in parallel to (1)H NMR study, which does not show any complex formation. In conclusion, the results of the studies with carbamazepine as a model drug showed the advantages of simultaneous use of solid phase microextraction and spectroscopic methods in protein binding studies and indicated complementary information, which can be obtained with the use of SPME. Furthermore, we show that SPME in combination with liquid chromatography-mass spectrometry permitted direct in vitro determination of plasma-protein binding and direct in vivo evaluation of inter-animal variability in free concentrations of carbamazepine at physiologically relevant concentrations, the type of experiments typically inaccessible by spectroscopic techniques due to poor sensitivity and different mode of implementation.
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Reuse of treated wastewater to irrigate agricultural crops is increasing in many arid and semi-arid areas around the world. The presence of numerous pharmaceutical and personal care products (PPCPs) in treated wastewater and their potential transfer into food produce such as vegetables poses an unknown human health risk. The goal of this study was to identify PPCPs that have a comparatively high potential for plant uptake and translocation. A total of 20 frequently-occurring PPCPs were compared for their accumulation into four staple vegetables (lettuce, spinach, cucumber, and pepper) grown in nutrient solutions containing PPCPs at 0.5 or 5μgL(-1). Triclocarban, fluoxetine, triclosan, and diazepam were found at high levels in roots, while meprobamate, primidone, carbamazepine, dilantin, and diuron exhibited more active translocation from roots to leaves. Root uptake of neutral PPCPs was positively correlated with the pH adjusted log Kow(i.e., log Dow), and was likely driven by chemical adsorption onto the root surfaces. In contrast, translocation from roots to leaves was negatively related to log Dow, suggesting hydrophilicity-regulated transport via xylems. Compounds preferentially sorbed to roots should be further evaluated for their uptake in tuber vegetables (e.g., carrot, radish) under field conditions, while those easily translocated into leaves (e.g., carbamazepine, dilantin) merit focused consideration for leafy and other vegetables (e.g., lettuce, cucumber). However, estimation of dietary intake by humans suggested the implied risks from exposure to PPCPs via wastewater irrigation to be negligible.