Adsorption onto granular activated carbon (GAC) is an established technology in water and advanced wastewater treatment for the removal of organic substances from the liquid phase. Besides adsorption, the removal of particulate matter by filtration and biodegradation of organic substances in GAC contactors has frequently been reported. The application of GAC as both adsorbent for organic micropollutant (OMP) removal and filter medium for solids retention in tertiary wastewater filtration represents an energy- and space saving option, but has rarely been considered because high dissolved organic carbon (DOC) and suspended solids concentrations in the influent of the GAC adsorber put a significant burden on this integrated treatment step and might result in frequent backwashing and unsatisfactory filtration efficiency. This pilot-scale study investigates the combination of GAC adsorption and deep-bed filtration with coagulation as a single advanced treatment step for simultaneous removal of OMPs and phosphorus from secondary effluent. GAC was assessed as upper filter layer in dual-media downflow filtration and as mono-media upflow filter with regard to filtration performance and OMP removal. Both filtration concepts effectively removed suspended solids and phosphorus, achieving effluent concentrations of 0.1 mg/L TP and 1 mg/L TSS, respectively. Analysis of grain size distribution and head loss within the filter bed showed that considerable head loss occurred in the topmost filter layer in downflow filtration, indicating that most particles do not penetrate deeply into the filter bed. Upflow filtration exhibited substantially lower head loss and effective utilization of the whole filter bed. Well-adsorbing OMPs (e.g. benzotriazole, carbamazepine) were removed by >80% up to throughputs of 8000-10,000 bed volumes (BV), whereas weakly to medium adsorbing OMPs (e.g. primidone, sulfamethoxazole) showed removals <80% at <5,000 BV. In addition, breakthrough behavior was also determined for gabapentin, an anticonvulsant drug recently detected in drinking water resources for which suitable removal technologies are still largely unknown. Gabapentin showed poor adsorptive removal, resulting in rapid concentration increases. Whereas previous studies classified gabapentin as not readily biodegradable, sustained removal was observed after prolonged operation and points at biological elimination of gabapentin within the GAC filter. The application of GAC as filter medium was compared to direct addition of powdered activated carbon (PAC) to deep-bed filtration as a direct process alternative. Both options yielded comparable OMP removals for most compounds at similar carbon usage rates, but GAC achieved considerably higher removals for biodegradable OMPs. Based on the results, the application of GAC in combination with coagulation/filtration represents a promising alternative to powdered activated carbon and ozone for advanced wastewater treatment.
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Tremor is a rhythmic, involuntary muscular contraction with consistency of rate, amplitude and pattern. It is the most common of all involuntary movements. Several systems for classifying tremor exist with the most frequent system classed according to behavioral context, ie, resting, postural and action. Clinical recognition of tremor type is extremely important as type determines prognosis, treatment and need for genetic counseling. The most common forms are parkinsonian, physiological, cerebellar intention and essential tremor. Essential or hereditary tremor is the most common of all neurologic conditions with 3-4 million Americans affected. Nursing implications of caring for essential tremor patients are presented.
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Changes within the immune system have been reported to contribute to the pathophysiology of bipolar disorder and epilepsy. Interestingly, overlapping results regarding the cytokine system have been found for both diseases, namely alterations of interleukins IL-1β, IL-2, IL-4, IL-6, and tumor necrosis factor-α (TNF-α). However, the effect of mood stabilizers and antiepileptic drugs (AEDs) on these cytokines has not been systematically evaluated, and their effect on IL-17 and IL-22, other immunologically important cytokines, has not been reported. Therefore, we systematically measured levels of IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22 and TNF-α in stimulated blood of 14 healthy female subjects in a whole blood assay using the toxic shock syndrome toxin TSST-1 as stimulant. Blood was supplemented with the mood stabilizers or antiepileptic drugs primidone (PRM), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), valproic acid (VPA), oxcarbazepine (OXC), topiramate (TPM), phenobarbital (PB), lithium, or no drug. IL-1β production was significantly decreased by PRM, CBZ, LEV, LTG, OXC, PB and lithium. IL-2 significantly decreased by PRM, CBZ, LEV, LTG, VPA, OXC, TPM and PB. IL-22 significantly increased by PRM, CBZ, LEV, OXC, TPM and lithium and decreased by VPA. TNF-α production significantly decreased under all applied drugs. The mechanism of action and side effects of mood stabilizers and AEDs may involve modulation of IL-1β, IL-2, IL-22 and TNF-α signaling pathways. IL-22 may be a research target for specific therapeutic effects of mood stabilizers and AEDs. These drugs might influence cytokine production by modulating ion channels and γ-aminobutyric acid (GABA) receptors of immune cells.
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A descriptive trial of essential tremor in Buenos Aires city is proposed. It may be considered as the first one like this in Latin America. During a 15 year period, sixteen families with essential tremor diagnosis have been examined, making a total of 39 patients (20 males and 19 females). The disease was basically studied from its semiological, clinico-evolutive and therapeutical view point, following a protocol. Our results indicate -- a. The clinico-evolutive characteristics: its frequency (according to race, sex, social status, age of beginning and physiopathological type), morbidity and mortality, evolution, prognosis, triggering factors, longevity and multiparity. b. The different treatment given to our patients with discussion of their pharmacokinetic and pharmacodynamic basis and evaluation of the best responses. In this matter, it is concluded that both primidone (750 mg/daily) and/or propranolol (160-240 mg/daily) are undeniably the drugs of first choice for the treatment of this disease. A comparison of the clinico-therapeutic features of this tremor in Buenos Aires and other cities is done. The study of this syndrome in Buenos Aires does not give different results from those obtained in Europe and USA.
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Successful treatment of partial complex seizures (and the epilepsies in general) is a process of management over time and involves several factors. It starts with accurate and adequate diagnostic formulations. To this end the physician must be thoroughly familiar with the ictal manifestations of partial complex and other epilepsies as well as the clinical features of other transient but reversible episodes that might present difficulties in differential diagnosis. The diagnosis is based upon the history of a patient experiencing partial complex seizures, and the most important resource is a careful and detailed history of the ictal events and the circumstances under which they occur. Clinical observation and electrophysiologic monitoring of the patient during attacks, either spontaneous or induced, is the most powerful technique available in cases which present difficult diagnostic problems. In addition to recognition and proper classification of the seizures themselves, diagnosis and treatment of the cause of the seizures, particularly when it is an active disease, is of prime importance. Even after accurate diagnosis, the heterogenous nature of the population of patients with partial complex seizures is such that marked variation in response to treatment with antiepileptic drugs is to be anticipated. The use of these drugs must be individualized and based upon a thorough and working knowledge of their clinical pharmacology. The most frequent mistakes in our experience have been prescribing the drugs in too little doses or for too short a time. Less often the problem is overmedication. The best indicator of the effectiveness of the drugs is the clinical response of the individual patient, and in general each drug should be prescribed in increasing doses until either the seizures are controlled or unacceptable degrees of toxicity develop. The use of serum level determinations can be very helpful if not invaluable, particularly in identifying and understanding potential adverse effects of the drugs. Patient noncompliance in adhering to drug schedules is widespread, but usually can be detected by measuring serum levels. Even with the most efficient use of the drugs, however, some patients will be intractable, and elective surgical treatment should be considered. Finally, control of seizure occurrence alone is not necessarily adequate treatment, as many patients will have difficult psychosocial problems associated with their epilepsy. Treatment of such associated problems is necessary on its own merits, but occasionally can result in significant improvement in seizure control.
The authors prospectively followed 662 pregnancies in women with epilepsy who used enzyme-inducing AED. Of the 667 neonates, 463 were exposed to carbamazepine, 212 to phenytoin, 44 to phenobarbital, 11 to primidone, and 7 to oxcarbazepine. The control subjects were 1,324 nonepileptic pregnancies (1,334 neonates) matched for maternal age, parity, number of fetuses, and delivery date. None of the mothers received vitamin K(1) during pregnancy, but all infants received 1 mg vitamin K(1) intramuscularly at birth.
A quantitative gas-liquid chromatographic procedure is described for the consecutive determination of phenytoin, phenobarbital, primidone, phenylethylmalondiamide, carbamazepine, trimethadione, dimethadione, ethosuximide and valproate from a single serum specimen of 1.2 ml. After extraction from serum by two different procedures, the anticonvulsants are chromatographed without further purification on a 3% OV 17 column either with or without derivative formation by means of "on-column" methylation. Multiple internal standards are employed in order to enhance the reproducibility of drug-concentration measurement.
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Tremor disorders are commonly encountered in the elderly. Physiological tremor is present in all of us and may be enhanced by drugs or other circumstances to cause symptomatic dysfunction. Essential tremor consists of postural and kinetic tremors which may involve the hands, head, and voice. Approximately 50% of cases are hereditary. Significant disability may occur. Propranolol and primidone provide effective treatment for some patients. The tremor of Parkinson's disease occurs in resting and postural positions. Treatment with levodopa usually reduces the tremor. Anticholinergics may also decrease tremor but often cause mental side effects in the elderly. Disturbances of the cerebellum may cause a kinetic tremor of the extremities or shakiness of the trunk. Tremors may also occur on a psychogenic basis. Proper classification of tremor disorder will lead to appropriate diagnosis and, often, effective treatment.
The concurrence of pregnancy and movement disorders is an uncommon event in a general neurologic practice. Even at specialized movement disorder referral centers, there is insufficient experience to adequately guide management of pregnancy, except perhaps in the case of WD. The questions posed most urgently by patients regard the safety of medication, an issue on which there is insufficient data, and their ability to care for a child for at least the next decade, an issue that differs by disease and social situation. The author's formulation of efficacy and toxicity suggests that certain medications commonly used in movement disorders should be discontinued before pregnancy, if possible. These medications include neuroleptics, amantadine, diazepam, primidone, selegiline, and reserpine. Pregnancy may unmask a pre-existing potential for chorea (i.e., chorea gravidarum) and frequently has a mild exacerbating effect on symptoms of PD; however, it has little effect on other movement disorders. Severe generalized dystonia would probably interfere with vaginal delivery, but the scant existing data suggest minimal effect of movement disorders on pregnancy, childbirth, and neonatal health.
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Our findings confirmed our hypothesis that primary bowing tremor is similar to primary writing tremor, with regard to phenomenology and epidemiology as well as tremor frequency. There was no difference in tremor frequency between conditions, suggesting that tremor is not influenced by bimanual coordination or bowing speed. Our findings thus provide new phenomenological aspects and may contribute to a better understanding of primary bowing tremor.
An automated gas-liquid chromatographic technique for the routine determination of phenobarbitone, primidone and phenytoin using a nitrogen-detector is described. The high selectivity of the detector for nitrogen-containing compounds allows a direct extraction procedure and the use of a phenytoin analogue as an internal standard obviates the need for accurate aliquot measurement after extraction. The anticonvulsants are chromatographed as methyl derivatives produced by on-column methylation with trimethylphenyl ammonium hydroxide following automatic liquid injection. Quality control data from an internal quality control scheme is presented and the performance of the laboratory in an inter-laboratory control scheme is reported and discussed.
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A total of 194 children of epileptic mothers and 71 children of epileptic fathers were examined for mental retardation, neurologic disturbances, major malformations, and acrofacial dysmorphias typical for hydantoin-barbiturate embryopathy (HB-E). HB-E was observed in nearly 7% of the children of mothers on anticonvulsants during pregnancy. Barbiturates and/or primidone were observed to induce the same dysmorphic features as hydantoins. The teratogenic potential of hydantoins may be slightly increased in combination with barbiturates/primidone. Neither the 71 children of epileptic fathers nor the 46 children of epileptic mothers without anticonvulsants exhibited symptoms of HB-E. The frequency of major, unspecific malformations was increased in children of epileptic mothers as well as in children of epileptic fathers as compared with the general population. Cerebral disturbances without dysmorphias were increased in children of mothers with and without anticonvulsants, but this was rarely the case in children of epileptic fathers. Cerebral disturbances were observed more often in children of mothers with seizures during pregnancy than in children of mothers without seizures. Multifactorial genetic influences on major malformations and influences of maternal seizures on cerebral disturbances in the offspring are likely.
Global water shortage is placing an unprecedented pressure on water supplies. Treated wastewater is a valuable water resource, but its reuse for agricultural irrigation faces a roadblock: the public concern over the potential accumulation of contaminants of emerging concern (CECs) into human diet. In the present study, we measured the levels of 19 commonly occurring pharmaceutical and personal care products (PPCPs) in 8 vegetables irrigated with treated wastewater under field conditions. Tertiary treated wastewater without or with a fortification of each PPCP at 250 ng/L, was used to irrigate crops until harvest. Plant samples at premature and mature stages were collected. Analysis of edible tissues showed a detection frequency of 64% and 91% in all vegetables from the treated wastewater and fortified water treatments, respectively. The edible samples from the two treatments contained the same PPCPs, including caffeine, meprobamate, primidone, DEET, carbamazepine, dilantin, naproxen, and triclosan. The total concentrations of PPCPs detected in edible tissues from the treated wastewater and fortified irrigation treatments were in the range of 0.01-3.87 and 0.15-7.3 ng/g (dry weight), respectively. Annual exposure of PPCPs from the consumption of mature vegetables irrigated with the fortified water was estimated to be only 3.69 μg per capita. Results from the present study showed that the accumulation of PPCPs in vegetables irrigated with treated wastewater was likely limited under field conditions.
The antiepileptic drugs phenobarbital and phenytoin were determined in serum by enzyme immunoassay (Emit, Syva Corp.) and gas-liquid chromatography. The Emit assays were mechanized by the use of an Eppendorf analyzer 5010. The precision of the Emit system was sufficient (coefficient of variation within series 6-13% and from day to day 8-15% with various calibrators and control sera). Moreover the Emit method is rapid, specific and easy to perform. The procedure requires only 10 microliter of serum per determination. A disadvantage however is the high cost of the reagents. A comparison of the results obtained by Emit and gas-liquid chromatography in a series of about 50 patients showed a good correlation between both methods (correlation coefficient r = 0.968 for phenobarbital and 0.978 for phenytoin).
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The pharmacokinetics and efficacy of the anticonvulsant primidone (PRM) and its active metabolites, phenobarbital (PB) and phenylethylmalonamide (PEMA), were studied after single-dose administration in mice. The half-life of PB is twice that of PRM and PEMA. The plasma/brain ratios provide evidence of poor penetration of PRM into brain. The results support our findings of negligible or absent PRM concentrations in the brains of patients on primidone therapy who were undergoing surgery for intractable epilepsy. The anticonvulsant properties of PRM, PB, and PEMA against maximal electroshock in mice were also studied with the use of the metabolic inhibitor SKF 525A. The half-life, potency, peak anticonvulsant effect, and effective dose curves of these compounds indicate that the anticonvulsant effect of short-term oral PRM administration in mice is from derived PB.
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Prolonged QT or QU intervals can be caused by a variety of conditions which include drugs, electrolyte imbalance, and acquired and congenital diseases. This finding is associated with life-threatening ventricular arrhythmias that, at times, have unusual morphologies characteristically named "torsade de pointes." Treatment, when iatrogenic, is obvious--when due to acute acquired diseases, therapy is supportive until the acute phase passes. In congenital prolonged QT syndromes, primidone (Mysoline) recently has been found to be successful in long-term management.
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Of a prospective study, "Epilepsy, pregnancy, and child development," children could be retraced at school age and adolescence. Sixty-seven were born to mothers with epilepsy [no drugs during pregnancy (n = 13), monotherapy (n = 31), polytherapy (n = 23)]; 49 were nonafflicted control children. Assessments included an intelligence test (Wechsler), a neurologic examination (Touwen), and an EEG. Data analyses were performed, controlling for parental social status, type of maternal drug therapy and drug dosage, type of epilepsy, frequency of seizures during pregnancy, the original subgroups, and specific drug effects.
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We studied 4 patients (14-21 years old) with continuous spike/wave epilepsy during slow wave sleep with visual evoked potentials (VEP) and somatosensory evoked potentials (SEP). All the patients presented the same focality and received the same medication (primidone plus sodium valproate). No case had another pathology not related with epilepsy which could alter the evoked potential findings. The results obtained in the initial evoked potentials were compared with those achieved after 5 years of treatment. In the initial study interhemispheric asymmetry in the latency of the early component (L.N1) of the SEP was observed with a mean of 10%. Five years later normal SEP were obtained with the asymmetry having disappeared thus leading to the deduction that the physiopathologic improvement found in these patients was due to the treatment of sodium valproate together with primidone.
The removal of trace organic compounds (TOrCs) and their biotransformation rates, kb (LgSS(-)(1)h(-)(1)) was investigated across different redox zones in a biological nutrient removal (BNR) system using an OECD batch test. Biodegradation kinetics of fourteen TOrCs with initial concentration of 1-36μgL(-)(1) in activated sludge were monitored over the course of 24h. Degradation kinetic behavior for the TOrCs fell into four groupings: Group 1 (atenolol) was biotransformed (0.018-0.22LgSS(-)(1)h(-)(1)) under anaerobic, anoxic, and aerobic conditions. Group 2 (meprobamate and trimethoprim) biotransformed (0.01-0.21LgSS(-)(1)h(-)(1)) under anoxic and aerobic conditions, Group 3 (DEET, gemfibrozil and triclosan) only biotransformed (0.034-0.26LgSS(-)(1)h(-)(1)) under aerobic conditions, and Group 4 (carbamazepine, primidone, sucralose and TCEP) exhibited little to no biotransformation (<0.001LgSS(-)(1)h(-)(1)) under any redox conditions. BNR treatment did not provide a barrier against Group 4 compounds.
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This was a retrospective, observational study of WWE age 15-44 years, of childbearing ability, prescribed an AED from July 1, 2011 to June 30, 2012, and who had an appointment at the University of Colorado Hospital Outpatient Neurology Clinic (Anschutz Medical Campus).
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We based this review on published aggregate data. The main outcomes measured were the proportions of patients achieving a 12-month remission from seizures, reporting adverse effects, and being withdrawn from the treatment they had been randomised to receive.
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In a 39-year-old woman an anticonvulsant therapy was initiated because of focal attacks in the left arm and face. The patient experienced generalized maculopapular skin rashes in response to each of four chemically similar anticonvulsant drugs: phenytoin, carbamazepine, primidone and clonazepam. During administration of carbamazepine the clinical features included fever, hepatitis and hematological eosinophilia in addition to the skin rash (anticonvulsant hypersensitivity syndrome). The anticonvulsant hypersensitivity syndrome is defined as an idiosyncratic reaction caused by disturbed drug metabolism. Positive lymphocyte-transformation tests with carbamazepine and phenytoin indicate an immunological mechanism underlying the rashes in our patient. Patch testing with the four anticonvulsant drugs gave positive results only with carbamazepine. Skin biopsy showed the histological features of a delayed-type allergy. The anticonvulsant therapy was continued with a chemically unrelated preparation, valproic acid; this drug is well tolerated and has proved appropriate for prevention of seizures.
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A spinn immunoassay for diphenylhydantoin is reported, which appears to give an accurate and precise estimate of serum diphenylhydantoin concentrations, as judged by the disappearance of [14C]diphenylhydantoin from the serum of a rabbit. The assay also appears to be a reliable technique for routine diphenylhydantoin determinations, as judged from our experience with 28 patients. Serum diphenylhydantoin concentrations in the range of 1.0-50.0 mg/liter are easily determined on a 50-mul sample. Except for primidone, no significant cross reactivity was observed with eight drugs that are commonly used in conjunction with diphenylhydantoin therapy. This fast, simple, and precise method therefore appears to be readily applicable to routine determination of diphenylhydantoin.
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A retrospective data analysis in 3 patients was performed.
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Pharmacokinetic interactions between antiepileptics represent a major potential complication of epilepsy treatment because drug combinations are common. This review discusses pharmacokinetic drug interactions of clinical significance involving antiepileptics and cytochrome P450 (CYP). Most commonly used antiepileptics are eliminated through hepatic metabolism, catalysed by the enzymes CYP2C9, CYP2C19 and CYP3A4 and uridine diphosphate glucuronosyltransferase (UDGPT). Antiepileptics are associated with a wide range of drug interactions, including hepatic enzyme induction and inhibition. Phenytoin, phenobarbiral, primidone and carbamazepine induce CYP and UDPGT enzymes while valproic acid inhibits them. Avoidance of unnecessary polypharmacy, selection of alternative agents with lower interaction potential and careful dosage adjustments based on serum drug concentration monitoring and clinical observation are the main methods for reducing the risks associated with these interactions.
Medical records of all patients with a primary or secondary diagnosis of laryngeal spasm or essential tremor treated with primidone between June 1, 2012, and March 21, 2014, at a tertiary care medical center were reviewed. Data analysis occurred in April 2014.