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The porcine esophageal mucosa has been proposed as a substitute for the buccal mucosa barrier on ex vivo permeability studies mainly due to its large surface area as well as its easier preparation. Therefore, this study compared the ex vivo permeability parameters of two drugs (carmabazepine (CBZ) and triamcinolone acetonide (TAC)) with different permeabilities and physicochemical properties through buccal and esophageal mucosae using a Franz diffusion cell system and HPLC as detection method. The freezing effects on drug permeability parameters were also evaluated by comparing them when fresh and frozen tissues were used. The barrier properties were not affected by the freezing process since the obtained parameters for both drugs were similar in frozen and fresh tissues (buccal and esophageal mucosae). However, an increase of CBZ retention was shown in frozen tissues. Fresh and frozen esophageal mucosae provided higher permeation of TAC than on buccal mucosae while the obtained permeability parameters for CBZ were similar on both mucosae. According to our results, porcine esophageal mucosa could be used as a substitute for buccal mucosa on ex vivo studies involving CBZ but not TAC. Frozen tissues could be used as substitute for fresh tissues in both cases. However, any substitution should be done with care and only if previous tests were performed, because the results could differ depending on the tested drug.
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Maternal use of antiepileptic drugs (AEDs) during pregnancy has been associated with an increased risk of congenital abnormalities in the fetus. This is partly attributable to AEDs. We aimed to analyse seizure frequency and the rate and type of any congenital malformation related to pregnancies in women with epilepsy in this prospective study. Eighty four pregnant women with epilepsy on AEDs were followed for congenital malformations. Z test was used for statistical analysis. Pregnancy did not influence the seizure frequency in 64 (76.2%) pregnancies. The seizure frequency increased in 16 (19.04%) pregnancies. In 4 (4.76%) pregnancies the number of seizures decreased during pregnancy. Overall percentage of congenital malformations in infants of mothers with epilepsy treated with AEDs was 10%, versus 3.65% in the general Turkish population. Percentages of malformations in children of pregnancies in women with epilepsy on antiepileptic drugs (AEDs) were; 6.52% (3/46) for carbamazepine (CBZ), 14.28% (2/14) for phenytoin (PHT), 13.33% (2/15)for valproic acid (VPA) and 20% (1/5) for phenobarbital (PB). This comfirms previous reports that all four AEDs (CBZ, PHT VPA, PB) are associated with an increased risk of congenital malformations, although CBZ seems to be the the safest agent in monotherapy.
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Benzodiazepines have been shown to have broad-spectrum activity, rapid onset of action, and a wide therapeutic window compared with other anxiolytic medications. Yet the use of benzodiazepines has been limited by concern regarding dependence, withdrawal, and abuse. Agents such as antidepressants, serotonergic anxiolytics, anticonvulsants, and beta-blockers have been used with varying degrees of success to help facilitate the tapering of benzodiazepines. Carbamazepine, imipramine, valproate, and trazodone have been beneficial in the management of benzodiazepine discontinuation, but not in decreasing the severity of benzodiazepine withdrawal. A stepwise approach to discontinuing benzodiazepines is offered.
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Patients who had uncontrolled pain with carbamazepine therapy and those who suffered adversely from its side effects were selected for this safe, simple and repeatable surgery. Pain-free periods were achieved for at least 2 years. Functional difficulty was not experienced in the affected numb areas. When it recurred, pain was less intense and was better controlled with a reduced dosage of carbamazepine. In four cases, after avulsion of the involved nerves, a suitable-sized titanium screw was inserted into the mental and infra-orbital foramina. Obturation of the foramen prevented nerve regeneration, which further prolonged the pain remission period.
A 3.5-year-old girl had epilepsia partialis continua of the right side. Clinical and laboratory findings were consistent with Rasmussen's encephalitis. Treatment with high-dose methylprednisolone led to temporary control of seizures, but for 2 years, the seizures remained refractory to phenobarbital, phenytoin, lorazepam, carbamazepine, valproic acid, vigabatrin, gabapentin, and lamotrigine. A 6-week course, and later a 6-month course, of intraventricular interferon-alpha almost totally suppressed the seizures. Although moderately hemiparetic, the child has reasonable neurologic function with mild speech delay. She is receiving her third course of treatment, and seizures remain completely controlled.
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For ambulatory pediatric outpatients,reports of abnormalities of bone metabolism associated with anti-epileptic drugs are inconsistent and may be difficult to interpret.
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The occurrence of eight pharmaceuticals (beta-blockers: acebutolol, atenolol, metoprolol and sotalol; antiepileptic: carbamazepine; fluoroquinolone antibiotics: ciprofloxacin, norfloxacin, ofloxacin) were assessed in the raw and treated sewage of 12 sewage treatment plants (STPs) in Finland. The average concentrations in the raw and treated sewage ranged from 100 to 1060 ng L(-1) and from <24 to 755 ng L(-1), respectively. The average daily loads ranged from 36 to 405 mg/1000 inh and from 2 to 302 mg/1000 inh, respectively. In the treatment plants, fluoroquinolones were eliminated by >80%. Carbamazepine was not eliminated during the treatment and in fact even higher concentrations were frequently found in the treated than in the raw sewages. The increase in concentration was shown to be most likely due to enzymatic cleavage of the glucuronic conjugate of carbamazepine and release of the parent compound in the treatment plant. The beta-blockers were eliminated in average by less than 65% and the elimination varied greatly between the treatment plants. Especially the dilution of raw sewage by rainwater and a consequent decrease in the hydraulic retention time of a treatment plant was found to deteriorate the elimination of the beta-blockers. The work shows that especially carbamazepine and the beta-blockers may reach the recipient waters and there is a need to enhance their elimination in the sewage treatment plants. In this attempt, a denitrifying biofilter as a tertiary treatment could be of minor importance since in this study it did not result in further elimination of the target compounds.
To evaluate the effect of monotherapy (phenytoin sodium (DPH) and carbamazepine (CBZ) on the threshold intensity (TI), cortical latency (CL), central conduction time (CCT), using transcranial magnetic stimulation (TMS). A single pulse transcranial magnetic stimulation was used for recording the motor-evoked potentials (MEP) from the thenar muscles of both hands, in 36 patients with well-controlled epilepsy on monotherapy, with normal EEG and imaging studies. The TI, CL, CCT and the MEP amplitude were recorded and compared with 20 healthy controls. The threshold intensity was significantly higher in patients on DPH, (P< 0.05) with a significant decrease in the MEP amplitude when compared with controls (P< 0.05). Anticonvulsants alter the excitability of human motor pathways in epileptic subjects. This effect differs among the drugs used; DPH had a greater depressant effect on the excitability than CBZ in the present study.
The primary objective of this study was to determine the presence of unregulated organic chemicals in reclaimed water using complementary targeted and broad spectrum approaches. Eleven of 12 targeted human pharmaceuticals, antioxidants, and plasticizers, and 27 tentatively identified non-target organic chemicals, were present in secondary effluent entering tertiary treatment trains at a wastewater treatment plant and two water reclamation facilities. The removal of these compounds by three different tertiary treatment trains was investigated: coagulant-assisted granular media filtration (California Title-22 water, 22 CCR 60301-60357; Barclay ), lime clarification/reverse osmosis (lime/ RO), and microfiltration-reverse osmosis (MF/RO). Carbamazepine, clofibric acid, gemfibrozil, ibuprofen, p-toluenesulfonamide, caffeine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and N-butyl benzenesulfonamide (N-BBSA) were present at low to high nanogram-per-liter levels in Title 22 water. The lime/RO product waters contained lower concentrations of clofibric acid, ibuprofen, caffeine, BHA, and N-BBSA (<10 to 71 ng/L) than their Title 22 counterparts. The MF/RO treatment reduced concentrations to levels below their detection limits, although BHT was present in MF/RO product water from one facility. The presence of the target analytes in two surface waters used as raw drinking water sources and a recharged groundwater was also examined. Surface waters used as raw drinking water sources contained caffeine, BHA, BHT, and N-BBSA, while recharged groundwater contained BHT, BHA, and N-BBSA. Nontarget compounds in recharged groundwater appeared to be attenuated with increased residence time in the aquifer.
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Paroxysmal kinesigenic dyskinesia (PKD) is a disorder that is characterised by brief episodes of involuntary movements triggered by other sudden movements.