bluuebunny/crossref_metadata_2025 huggingface dataset:
MANAGERIAL AUTONOMY, CONTRACTUAL INCENTIVES AND PRODUCTIVITY IN A TRANSITION ECONOMY: SOME EVIDENCE FROM CHINA'S TOWN AND VILLAGE ENTERPRISES
Authors: Cheng Harrison , Hsiao Cheng , Nugent Jeffrey B. , Qiu Jicheng
Published: September 2006

Abstract.  In advanced industrial economies it is accepted that efficiency requires aligning managerial autonomy in decision‐making with managerial incentives. Should this hold for economies like that of rural China where (at least until very recently) managers might abuse autonomy and government owners may have objectives other than profit maximization? This paper tests for the effects of managerial autonomy on efficiency with and without alignment with incentives in a panel of Chinese town and village enterprises (TVEs). The results show that managerial autonomy has had a positive and significant effect on productivity only when aligned with incentives.
INFANT INDUSTRY AND POLITICAL ECONOMY OF TRADE PROTECTION
Authors: Xu Bin
Published: September 2006

Abstract.  This paper introduces infant‐industry considerations in political economy determination of trade protection. I build a model where the government cares about both political contributions and national welfare. A potentially beneficial high‐tech industry is not viable in the country whose initial human capital is low. In the political economy equilibrium, we find that the tariff schedule will be V‐shaped: it decreases initially to maintain the viability of the industry but increases thereafter as the industry expands and gains political power. We use the model to explain both China's tariff offers in WTO negotiations and GATT/WTO rules regarding developing countries.
FACTOR ACCUMULATION AND THE TERMS OF TRADE: APPLICATIONS TO THE ASIAN FINANCIAL CRISIS
Authors: Choi E. Kwan , Beladi Hamid
Published: September 2006

Abstract.  This paper investigates the effects of population growth and capital accumulation on trade and welfare. In the absence of a terms of trade effect, an population increase reduces the standard of living and causes a reduction in welfare. An increase in population causes deterioration in the terms of trade of a labour abundant country, whereas capital accumulation improves them, regardless of the source of growth. Moreover, an increase in the South's population is immiserizing.
BARTER'S ROLE IN THE MONEY–INCOME RELATIONSHIP
Authors: Marvasti Akbar , Smyth David J.
Published: September 2006

Abstract.  This paper deals with a reassessment of the money–income relation and predictability of changes in GDP with innovations in money in the presence of barter. Organized barter as a method of transaction, through barter exchanges, has been growing rapidly in the US economy. With the introduction of computers and the use of a credit system which allows non‐simultaneous transactions, barter exchanges have found new opportunities to offer an alternative to monetary transactions. Analysis of data from the 1974–96 period provides some evidence suggesting that inclusion of barter in the output function improves the marginal predictability of money.
EFNS guidelines on management of restless legs syndrome and periodic limb movement disorder in sleep
Authors: Vignatelli L. , Billiard M. , Clarenbach P. , Garcia‐Borreguero D. , Kaynak D. , Liesiene V. , Trenkwalder C. , Montagna P.
Published: September 2006

In 2003, the EFNS Task Force was set up for putting forth guidelines for the management of the Restless Legs Syndrome (RLS) and the Periodic Limb Movement Disorder (PLMD). After determining the objectives for management and the search strategy for primary and secondary RLS and for PLMD, a review of the scientific literature up to 2004 was performed for the drug classes and interventions employed in treatment (drugs acting on the adrenoreceptor, antiepileptic drugs, benzodiazepines/hypnotics, dopaminergic agents, opioids, other treatments). Previous guidelines were consulted. All trials were analysed according to class of evidence, and recommendations formed according to the 2004 EFNS criteria for rating. Dopaminergic agents came out as having the best evidence for efficacy in primary RLS. Reported adverse events were usually mild and reversible; augmentation was a feature with dopaminergic agents. No controlled trials were available for RLS in children and for RLS during pregnancy. The following level A recommendations can be offered: for primary RLS, cabergoline, gabapentin, pergolide, ropinirole, levodopa and rotigotine by transdermal delivery (the latter two for short‐term use) are effective in relieving the symptoms. Transdermal oestradiol is ineffective for PLMD.
Placebo‐controlled trial of riluzole in multiple system atrophy
Authors: Seppi K. , Peralta C. , Diem‐Zangerl A. , Puschban Z. , Mueller J. , Poewe W. , Wenning G. K.
Published: September 2006

We performed a placebo‐controlled cross‐over trial of riluzole (100 mg b.i.d.) in 10 patients with probable multiple system atrophy (MSA) administering riluzole and placebo for 4 weeks each with a 4‐week washout period. Outcome measures evaluated short‐term anti‐Parkinsonian effects using the Unified Parkinson's Disease Rating Scale (UPDRS) subscales (UPDRS‐II, activities of daily living; UPDRS‐III, motor examination; sum of UPDRS‐II and ‐III) before and at the end of each treatment phase. Delta values were calculated by subtracting the UPDRS scores measured at the end of each treatment arm from those before onset of each medication phase. Riluzole was generally well tolerated. There were no significant anti‐Parkinsonian effects of riluzole comparing the UPDRS delta values for both treatment arms using the Wilcoxon signed‐rank test. It is unlikely that riluzole treatment could have clinically meaningful anti‐Parkinsonian effects in MSA. A trial assessing the disease‐modifying potential of riluzole in MSA is underway.
Epidemiological and clinical manifestations of patients hospitalized with brown recluse spider bite
Authors: Dyachenko P , Ziv M , Rozenman D
Published: September 2006

Background  Necrotic arachnidism represents a common health problem and standard treatments are usually safe and effective.

Objective  The aim of this study was to review documented Loxosceles species spider envenomations and identify the natural history of affected patients.

Methods  A retrospective single‐centre study included 52 patients with necrotic arachnidism hospitalized in the dermatology department between 1997 and 2004. We examined the relationship between the epidemiological, clinical and laboratory parameters and degree of lesion severity, length of hospitalization and time to complete healing.

Results  The bites occurred predominantly in rural areas, 67% between April and August. Only 35% of the patients sought medical care within 24 h post bite. Most bites were of the extremities (67%). Time to complete healing ranged from 14 days to more than 8 weeks (mean, 4.8 weeks). A marked relationship was found between age, comorbidities, lesion severity and time to complete healing (P < 0.01). Duration of hospitalization was significantly longer in patients with severe thigh lesions (P < 0.02).

Conclusions  Loxosceles species spider bites frequently induce necrotic, slowly healing ulcers on the fatty areas of the body. Early, appropriate systemic therapy may provide clinical benefit.
The natural compound n‐butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo3
Authors: Tsai Nu‐Man , Chen Yi‐Lin , Lee Chau‐Chin , Lin Po‐Chen , Cheng Yeung‐Leung , Chang Wen‐Liang , Lin Shinn‐Zong , Harn Horng‐Jyh
Published: September 2006

The naturally‐occurring compound, n‐butylidenephthalide (BP), which is isolated from the chloroform extract of Angelica sinensis (AS‐C), has been investigated with respect to the treatment of angina. In this study, we have examined the anti‐tumor effects of n‐butylidenephthalide on glioblastoma multiforme (GBM) brain tumors both in vitro and in vivo. In vitro, GBM cells were treated with BP, and the effects of proliferation, cell cycle and apoptosis were determined. In vivo, DBTRG‐05MG, the human GBM tumor, and RG2, the rat GBM tumor, were injected subcutaneously or intracerebrally with BP. The effects on tumor growth were determined by tumor volumes, magnetic resonance imaging and survival rate. Here, we report on the potency of BP in suppressing growth of malignant brain tumor cells without simultaneous fibroblast cytotocixity. BP up‐regulated the expression of Cyclin Kinase Inhibitor (CKI), including p21 and p27, to decrease phosphorylation of Rb proteins, and down‐regulated the cell‐cycle regulators, resulting in cell arrest at the G0/G1 phase for DBTRG‐05MG and RG2 cells, respectively. The apoptosis‐associated proteins were dramatically increased and activated by BP in DBTRG‐05MG cells and RG2 cells, but RG2 cells did not express p53 protein. In vitro results showed that BP triggered both p53‐dependent and independent pathways for apoptosis. In vivo, BP not only suppressed growth of subcutaneous rat and human brain tumors but also, reduced the volume of GBM tumors in situ, significantly prolonging survival rate. These in vitro and in vivo anti‐cancer effects indicate that BP could serve as a new anti‐brain tumor drug.
Fourteen polymorphic microsatellite DNA markers for the human malaria parasite Plasmodium vivax
Authors: KARUNAWEERA N. D. , FERREIRA M. U. , HARTL D. L. , WIRTH D. F.
Published: September 2006

We have optimized a set of 14 polymorphic microsatellite markers for the human malaria parasite Plasmodium vivax, all of them consisting of either tri‐ or tetranucleotide repeats. These markers, whose polymerase chain reaction amplification conditions are identical, were used to screen 25 parasite isolates from malaria‐endemic areas in Sri Lanka. The total number of alleles per locus ranged between 6 and 13 (average, 7.8), and expected heterozygosity ranged from 0.627 to 0.913 (average, 0.790). These markers are now being used to characterize the population structure of P. vivax in other endemic areas.
Eight new microsatellite markers in Atlantic cod (Gadus morhua L.) derived from an enriched genomic library
Authors: WESMAJERVI METTE SERINE , TAFESE TEKLE , STENVIK JØRGEN , FJALESTAD KJERSTI TURID , DAMSGÅRD BØRGE , DELGHANDI MADJID
Published: September 2006

One hundred and fifty random clones from an enriched genomic library of Atlantic cod were sequenced. Primer pairs were designed for 15 microsatellites containing perfect di‐, tri‐, tetra‐ and hexanucleotide repeats and characterized in 96 unrelated fish. Eight markers were successfully amplified, with the number of alleles ranging from two to nine per locus and observed heterozygosity ranging from 0.341 to 0.977. Loci Gmo‐G13 and Gmo‐G14 had a significant excess of homozygotes. All loci conformed to the Hardy–Weinberg equilibrium. Genetic linkage disequilibrium analysis between all pairs of the loci showed no significant departure from the null hypothesis between any of the loci.
Farmers’ Preferences for New Environmental Policy Instruments: Determining the Acceptability of Cross Compliance for Biodiversity Benefits
Authors: Davies Ben B. , Hodge Ian D.
Published: September 2006

This paper addresses the issue of farmers’ views concerning the perceived legitimacy of environmental cross compliance as a governance mechanism. Recent work on the theory of regulation emphasises the importance of the legitimacy ascribed to a regulation in determining the effectiveness with which it can be implemented. The current study outlines a rationale for why this motivational question should receive attention in economic studies of policy design and reports the results of a survey of 102 arable farmers in East Anglia, UK, which investigated the level of support for the principle of cross compliance for biodiversity objectives. It was found that two attitudinal factors, referred to as ‘Stewardship Orientation’ and ‘Technological Beliefs’, were by far the most significant in determining the acceptability of cross compliance in the sample, and that structural and socio‐demographic factors were considerably less important. The study also identified clusters of farmers according to their overall attitudinal orientation. Of the five groups thus categorised, four appeared on average likely to reject cross compliance as a general principle, leaving only the most ‘Environmental’ cluster in support. The policy implications are discussed and some conclusions drawn.
Assessing CAP Reform: Sensitivity of Modelling Decoupled Policies
Authors: Gohin Alexandre
Published: September 2006

The European Union reformed farm policy in June 2003 towards the decoupling of farm income support instruments. Available impact studies find that this reform reduces production incentives substantially for beef and to a lesser extent for arable crops. However, these studies assume that the previous reform, under Agenda 2000, already decoupled arable crop direct payments to a considerable extent, while beef premiums were linked more closely to production. Our main objective in this paper is to test the sensitivity of these results to this questionable modelling of Agenda 2000 direct payments, which neglects eligibility rules and land market imperfections. Our analysis reveals that the effects of the reform on both arable crop and beef production are always negative, however the Agenda 2000 direct payments are modelled. On the other hand, we show that, when the eligibility rules and land market imperfections are acknowledged, the production reducing effects may be much larger for arable crops than for beef. Policy implications of these results are noted.
Non‐parametric Modelling of Spatial Price Relationships
Authors: Serra Teresa , Goodwin Barry K. , Gil José M. , Mancuso Anthony
Published: September 2006

We apply non‐parametric methods to a consideration of price transmission processes within US egg markets at the turn of the nineteenth century. Gordon (National Bureau of Economic Research Working Paper 7833, 2000) labelled this as an era of ‘Great Inventions’ which contributed to the subsequent years of significant productivity growth and noted that the development of mechanical refrigeration and transportation technologies played an important role in this growth. Our models present certain advantages relative to parametric models traditionally employed in price transmission analyses. We compare results derived from local polynomial modelling with those obtained using non‐linear threshold models. Both techniques suggest that US egg markets were interrelated at the turn of the nineteenth century. However, non‐parametric techniques often suggest a higher degree of price transmission than that implied by threshold models. Results also suggest that threshold models may have difficulties in adequately capturing price relationship dynamics, especially when these are of a highly nonlinear nature.
The Impact of Electronic Clock Auction Systems on Shellfish Prices: Econometric Evidence from a Structural Change Model
Authors: Guillotreau Patrice , Jiménez‐Toribio Ramón
Published: September 2006

Economic theory suggests that different auction systems may lead to different price equilibria under specific conditions. By changing the trading rules, the introduction of electronic clock auction systems (ECAS) on primary fish markets is likely to modify the price formation process. A relationship between the prices of live prawns (Nephrops norvegicus) in two French ports where different ECAS have been successively introduced is estimated through two univariate models and a vector autoregressive model applied to stationary weekly data series. Using a recent multiple break searching procedure (Econometrica, Vol. 66, 1998, 47; Journal of Applied Econometrics, Vol. 18, 2003, 1; Econometrics Journal, Vol. 6, 2003, 72), a single structural change matching the date of implementation is discovered in the two ports and shows a different impact partly explained by the type of auction system in force. The introduction of the Euro in January 2002 also appeared to play an influential role in the adoption of electronic clock auction markets.
The Social Value of Seascapes in the Jurien Bay Marine Park: An Assessment of Positive and Negative Preferences for Change
Authors: McCartney Abbie
Published: September 2006

The Jurien Bay Marine Park, Australia, is known for its pristine seascapes, including views of the ocean and of the coastline. To aid the management of the various seascapes, this paper estimates aspects of the social value of these seascapes through the use of a contingent valuation study. Positive and negative preferences for change were accommodated within the survey design and model estimation. A single‐function extended spike model was employed to estimate the willingness to pay (WTP) for protection of the seascapes, and was later constrained to a restricted version of a spike model. The restricted model identified that a proportion of the population had a positive preference for change within the seascapes, but a larger proportion had a negative preference, resulting in a positive net WTP to maintain seascapes in their current condition. Seascapes with coastal views were determined as having the highest social value; however, the value of the ocean seascapes followed closely behind. The positive welfare estimate for natural seascapes provides a reason for their preservation.
Spontaneous Recurrent Seizures in Rats: Amino Acid and Monoamine Determination in the Hippocampus
Authors: Cavalheiro E. A. , Fernandes M. J. , Turski L. , Naffah‐Mazzacoratti M. G.
Published: September 2006

Summary: Rats subjected to structural brain damage induced by sustained convulsions triggered by systemic administration of pilocarpine (PILO) are a useful model for investigation of the mechanisms essential for seizure generation and spread in rodents. After PILO administration, three distinct phases are observed: (a) an acute period of 1–2 days’ duration corresponding to a pattern of repetitive limbic seizures and status epilepticus; (b) a seizurefree (silent) period characterized by a progressive return to normal EEG and behavior of 4–44 days’ duration; and (c) a period of spontaneous recurrent seizures (SRS) starting 5‐45 days after PILO administration and lasting throughout the animal's life. PILO (320–350 mgikg intraperitoneally, i.p.) was administered to rats, and the content of hippocampal monoamines and amino acids was measured in the acute, silent, and SRS periods by liquid chromatography. Norepinephrine (NE) level was decreased during all periods whereas dopamine (DA) content was increased. Serotonin (5‐hydroxytryptamine, 5‐HT) was increased only in the acute period. Utilization rate measurement of monoamines showed increased NE consumption and decreased DA consumption during all phases. 5‐HT utilization rate was increased only in the acute period. Amino acid content showed a decrease in aspartate (ASP) and glutamate (GLU) concentrations associated with increased y‐aminobutyric acid (GABA) level during the acute period. The silent phase was characterized by a decrease in glycine (GLY) and GABA levels and an increase in GLU concentration. The SRS period showed an increase in all amino acid concentrations. These findings show important neurochemical changes in the course of establishment of an epileptic focus after brain damage induced by status epilepticus triggered by pilocarpine.
Family History of Seizures in Posttraumatic and Alcohol‐Associated Seizure Disorders
Authors: Schaumann B. A. , Annegers J. F. , Johnson S. B. , Moore K. J. , Lubozynski M. F. , Salinsky M. C.
Published: September 2006

Summary: The potential role of genetic factors in the etiology of posttraumatic and alcohol‐associated seizures was studied in 289 male patients with recurrent seizures and in 174 individuals who had never experienced a seizure. The incidence of seizures in first‐degree relatives of probands was compared with that in relatives of unaffected individuals. Relatives of patients with alcoholassociated seizures had a rate ratio of 2.45 [95% confidence interval (CI) 1.41–4.251, whereas no excess incidence was noted among relatives of posttraumatic epilepsy patients (rate ratio 1.20, 0.64–2.25 CI). Relatives of probands with both antecedents showed an intermediate rate ratio of 1.72 (0.92–3.20 CI). Among probands with alcohol‐associated seizures, the rate ratio of 2.05 for patients with alcohol‐related seizures (i.e., spontaneously occurring seizures in association with chronic alcohol abuse) was slightly higher than that of 1.85 for probands with alcohol withdrawal seizures. Trauma severity had a slight impact on the incidence of affected relatives; patients with severe head injuries had a rate ratio of 0.73 and probands with milder trauma had a rate ratio of 0.99. The results indicate a limited, if any, role of genetic predisposition in development of posttraumatic seizures. Alcoholrelated seizures, however, showed familial aggregation of unprovoked seizures, suggesting an involvement of genetic factors in the origin of such seizures.
Clinical Trials of Antiepileptic Drugs Performed in the Private Practice Setting
Authors: Beran Roy G. , Tilley Michelle
Published: September 2006

Summary: Clinical trials of antiepileptic drugs (AEDs) are usually performed only in major teaching centers, thus ignoring the very real contribution available from private practice. The relation between the consultant and the referring family physician is often much closer in private practice, allowing much earlier recruitment of de novo patients into clinical trials. Between October 1988 and February 1992, 50 subjects were entered into various clinical trials including gabapentin (both an open add‐on trial and parallel‐arm add‐on study in generalized epilepsies), vigabatrin (placebo‐controlled cross‐over study in focal epilepsies), and lamotrigine (both placebo‐controlled cross‐over add‐on studies and parallel‐arm comparative monotherapy study in newly diagnosed patients with epilepsy). All these trials were coordinated in private neurologic practice in Sydney, Australia, as part of either national or international multicenter AED studies. The experience demonstrated the improved ease of recruitment and patient liaison available in the private sector. It also highlighted the very real logistic problems, such as the need for a noninstitutional‐based ethics committee, the training of support staff and a modified primary information resource system. Inclusion of private practice centers in clinical trials demonstrates the potential for improved patient recruitment and administrative management, especially in studies requiring newly diagnosed patients.
Lack of Interaction of Gabapentin with Carbamazepine or Valproate
Authors: Radulovic Louis L. , Wilder B. J. , Leppik Ilo E. , Bockbrader Howard N. , Chang Tsun , Posvar Edward L. , Sedman Allen J. , Uthman Basim M. , Erdman Gary R.
Published: September 2006

Summary: Gabapentin (GBP) studies were conducted in patients with epilepsy receiving carbamazepine (CBZ, n= 12) or valproate (VPA, n = 14) monotherapy. The effects of GBP coadministration on steady‐state CBZ or VPA concentrations and of these antiepileptic drugs (AEDs) on GBP pharmacokinetics were investigated. GBP (400 mg) was coadministered every 8 h for 3% days with CBZ or for 5 1/3 days with VPA. GBP was well tolerated. Mean steady‐state plasma CBZ/CBZ‐10, ll‐epoxide (CBZ‐E) and serum VPA concentrations before, during, and after GBP administration were not significantly different. Mean steady‐state GBP pharmacokinetic parameters during CBZ or VPA coadministration were similar to steady‐state parameters reported in healthy subjects. Thus, no pharmacokinetic interaction exists between CBZ or VPA and GBP. No dosage adjustment is necessary when GBP and CBZ or VPA are coadministered.
Effects of Valproate and Citrulline on Ammonium‐Induced Encephalopathy
Authors: Stephens Jeffrey R. , Levy René H.
Published: September 2006

Summary: Hyperammonemia is a recognized side effect of treatment with the antiepileptic drug (AED) valproate (VPA). Encephalopathic complications have also been observed in some patients receiving VPA therapy. The relation between VPA‐induced hyperammonemia and encephalopathy is not clear, however. A model of ammonium (NH4,+)‐induced coma was used to investigate the contribution of VPA and to assess the efficacy of citrulline (a urea cycle intermediate) on hyperammonemia and encephalopathy. In groups of 6–12 rats, administration of VPA (2.5 mmol/kg) was associated with (a) a decrease in the dose of NH4+ that produces coma in 50% of the animals (CD50) from 6.1 to 3.6 mmol/kg, and (b) significant increases in blood ammonia concentrations in NH4,+ treated animals. In addition, clear evidence also showed that in the presence of VPA, a lesser concentration of ammonia produced coma. Citrulline treatment (5. 0 mmol/ kg) was associated with (a) an increase in the CD50 value of NH4,+treated animals from 6.1 to 8.6 mmolikg, (b) a statistically significant decrease in ammonia concentration at all doses examined, (c) complete protection from encephalopathic effects of NH, + at citrulline concentrations threeto tenfold greater than basal levels; and (d) a 24% increase in the CD, value and a statistically significant decrease in ammonia concentration of VPA/NH4,+ treated animals. These findings indicate that VPA has a dual effect on encephalopathy and that citrulline should benefit those patients treated with VPA who experience adverse encephalopathic effects.
Hyponatremia Associated with Carbamazepine and Oxcarbazepine Therapy: A Review
Authors: Van Amelsvoort Th. , Bakshi R. , Devaux C. B. , Schwabe S.
Published: September 2006

Summary: Hyponatremia, an electrolyte disturbance usually without clinical significance, may sometimes lead to serious complications when overlooked or not treated appropriately. One cause of hyponatremia, the syndrome of inappropriate antidiuretic hormone (SIADH) secretion, has been associated with some drugs, including carbamazepine (CBZ). Because of its antidiuretic effects, CBZ has been used successfully to treat diabetes insipidus centralis. Possible mechanisms for the antidiuretic effects of CBZ have been proposed. Altered sensitivity to serum osmolality by the hypothalamic osmoreceptors appears likely, but an increased sensitivity of the renal tubules to circulating ADH cannot be excluded. CBZ has led to hyponatremia in patients with epilepsy, neuralgia, mental retardation, and psychiatric disorders with a frequency varying from 4.8 to 40%. Oxcarbazepine (OCBZ), which is structurally related to CBZ, has shown similar hyponatremic effects, but whether hyponatremia occurs more often than with CBZ is not yet clear. Experience with OCBZ is still limited, and there is no definite explanation for a possible difference in antidiuretic potency. Most patients with CBZiOCBZ‐induced hyponatremia are asymptomatic. In rare cases, water intoxication has been reported, necessitating treatment discontinuation.
Acute Oral Loading of Carbamazepine‐CR and Phenytoin in a Double‐Blind Randomized Study of Patients at Risk of Seizures
Authors: Van Der Meyden C. H. , Kruger A. J. , Müller F. O. , Rabie W. , Schall R.
Published: September 2006

Summary: The serum levels and side effects of, an acute oral loading dose‐schedule of carbamazepine (C) divitabs [CBZ controlled release (CR)] and phenytoin (PHT) were assessed in patients at risk of seizures. CBZ‐CR and PHT were administered to 42 adult patients (21 each) at a dosage of 20 mg/kg with a minimum and maximum dosage of 1,200 and 1,600 mg in patients weighing 80 kg, respectively. CBZ‐CR was given as single loading dose; PHT was split, with two thirds of the dose administered at 0 h and one third administered 2 h later. The 24‐and 36‐h doses were assessed according to the nystagmus status at 24 h. Mean CBZ serum levels (percentage of subjects with level >4 μg/ml shown in parentheses) were 0.0 (0%), 5.2 (62%), 6.7 (81%), 6.8 (95%), and 6.1 μg/ml(95%) at 0, 4, 8, 24, and 48 h after loading, respectively, and mean PHT levels (percentage of subjects with PHT level >10 μg/ml in parentheses) were 0.1 (0%), 13.2 (86%), 16.3 (loo%), 16.3 (l00%), and 15.4 pg/ml (82%). One subject in the CBZ group and 3 in the PHT group vomited. Clinical effects did not differ significantly between treatment groups and are reported. Acute doses of CBZ‐CR 20 mg/kg and PHT 20 mg/kg (two‐thirds at 0 h and one‐third at 2 h) provided therapeutic levels in most patients in G4 h and were well tolerated.
Effects of Carbamazepine on Murine Humoral and Cellular Immune Responses
Authors: Andrade‐Mena C. E. , Sardo‐Olmedo J. A. J. , Ramírez‐Lizardo E. J.
Published: September 2006

Summary: Oral administration of carbamazepine (CBZ)(15, 10, or 5 mg/kg) to mice significantly decreased both humoral and cellular immune responses evaluated by enumeration of direct and indirect plaque‐forming spleen cells (PFC) and delayed–type hypersensitivity reaction (DTH) against sheep red blood cells (SRBC) as compared with those observed in normal control animals. Moreover, spleen T cells obtained from CBZ–treated donor mice were capable of decreasing both PFC and DTH responses of normal spleen cells transferred into lethally irradiated recipient animals. The immunodepressor effect of CBZ was observed even though administration of CBZ induced augmentation of spleen cellularity.
Carbamazepine Effects on Afterdischarge, Memory Retrieval, and Conditioned Avoidance Response Latency in Hippocampally Kindled Cats
Authors: Majkowski J. , Dlawichowska E. , Sobieszek A.
Published: September 2006

Summary: Carbamazepine (CBZ) effects on (a) complex partial seizures and afterdischarges (AD), (b) memory retrieval, and (c) conditioned avoidance response (CAR) latencies were studied in a group of 9 hippocampally kindled cats. Significant AD and epileptic seizure suppression was observed in kindled cats after administration of CBZ concurrent with significant improvement in percentage scores on the memory retrieval test. The CAR latencies were longer in kindled cats with or without CBZ than in the conditioned group of cats without both kindling and CBZ. CAR latencies were not significantly different between kindled and kindled–CBZtreated cats. Thus, the longer latencies in kindled animals cannot be due to CBZ but apparently are related to the effects of kindling. In some kindled animals, longer CAR latencies were reversed by CBZ.
Lorazepam‐Valproate Interaction: Studies in Normal Subjects and Isolated Perfused Rat Liver
Authors: Anderson Gail D. , Gidal Barry E. , Kantor Eric D. , Wilensky Alan J.
Published: September 2006

Summary: Valproate (VPA) has been shown to interact with all the major antiepileptic drugs (AEDs) through two mechanisms of action: displacement from albumin binding sites and inhibition of drug metabolism. More recently, evidence showed that VPA inhibits the elimination of drugs metabolized by glucuronide conjugation. Lorazepam (LZP), which is primarily eliminated by conjugation with glucuronic acid, is administered concurrently with VPA both in treatment of epilepsy and in patients treated with VPA for psychiatric disorders. Therefore, a significant drug interaction is likely. We investigated such interaction both in in vitro isolated perfused rat liver (IPRL) and in normal subjects. LZP [2 mg, intravenous (i.v.) bolus] was administered to 8 normal volunteers before and after chronic dosing with VPA. In 6 of 8 subjects, VPA significantly decreased LZP plasma clearance by an average of 40% (p < 0.05) and increased LZP concentrations by decreasing formation clearance of the LZP glucuronide. In the IPRL studies, VPA also significantly decreased formation of LZP glucuronide (from 0.72 + 0.14 to 0.22 ± 0.15 ml/h/kg, p < 0.05), indicating that IPRL is a useful tool for evaluation of the effect of VPA on drugs eliminated by glucuronide conjugation.
Pharmacokinetics and Pharmacodynamics of Valproate Analogues in Rats. IV. Anticonvulsant Action and Neurotoxocity of Octanoic Acid, Cyclohexanecarboxylic Acid, and 1‐Methyl‐1 ‐Cyclohexanecarboxylic Acid
Authors: Liu Mei‐jen , Pollack Gary M.
Published: September 2006

Summary: We examined the pharmacodynamics of valproate (VPA) and three structural analogues, octanoic acid (OA), cyclohexanecarboxylic acid (CCA), and 1‐methyl‐1‐cyclohexanecarboxylic acid (MCCA) in rats. A pentylenetetrazol (PTZ) infusion seizure model was used to determine threshold convulsive doses of PTZ; the increase in PTZ threshold dose after administration of test compound was taken as an index of anticonvulsant activity. Each of the compounds investigated antagonized PTZ‐induced seizures, with MCCA evidencing the highest potency. Both CCA and MCCA appeared to have an approximate twofold advantage relative to VPA in protective index (i.e., the ratio of concentrations that produce toxicity to concentrations that produce anticonvulsant effect), based on a rotorod assay of neurotoxicity. Examination of the time course of PTZ antagonism indicated that there was significant dissociation between pharmacokinetics and pharmacodynamics of VPA, with a marked delay in production of maximal anticonvulsant activity. In contrast, only a slight delay in production of maximal protection against PTZ‐induced seizures was observed for MCCA, and no delay was evident for CCA. The data indicate that the dynamics of anticonvulsant action differ between these low‐molecular‐weight carboxylic acids despite their similar chemical structures.
Therapeutic Safety Monitoring: What to Look for and When to Look for It
Authors: Harden Cynthia L.
Published: September 2006

Summary: This review focuses on the safety problems associated with antiepileptic drugs (AEDs) as revealed by laboratory testing and clinical examination. There are two classes of side effects: (a) common and mild and (b) rare and severe. Allergic reactions to AEDs are common and usually mild. However, on rare occasions, they can progress to more severe cutaneous disorders, including Stevens‐Johnson syndrome and toxic epidermal necrolysis. Severe allergic reactions to AEDs range from immune responses with fever to multiorgan dysfunction. Allergic rashes may be genetically or immunologically determined. Laboratory abnormalities produced by AEDs are common and mild, and include hepatic enzyme elevation associated with phenytoin and mild elevation in ammonia associated with valproate. Serious, although rare, idiosyncratic side effects, such as aplastic anemia, hepatotoxicity, and thrombocytopenia, have also occurred with AEDs. These reactions are largely confined to the “classic” AEDs. With the exception of felbamate, AEDs approved in the past decade have not been plagued by severe idiosyncratic reactions. Subtle endocrine abnormalities, including variations in thyroid function tests and bone metabolism, and the often subclinical effects on peripheral nerve conduction produced by phenytoin and carbamazepine, are also examined.
Three Brief Epileptic Seizures Reduce Inhibitory Synaptic Currents, GABAACurrents, and GABAA‐Receptor Subunits
Authors: Evans M. Steven , Cady Craig J. , Disney Kimberly E. , Yang Li , LaGuardia James J.
Published: September 2006

Summary: Purpose:Cellular mechanisms activated during seizures may exacerbate epilepsy. γ‐Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in brain, and we hypothesized that brief epileptic seizures may reduce GABA function.

Methods:We used audiogenic seizures (AGSs) in genetically epilepsy‐prone rats (GEPRs) to investigate effects of seizures on GABA‐mediated inhibition in the presence of epilepsy. GEPRs are uniformly susceptible to AGSs beginning at 21 postnatal days. AGSs are brief convulsions lasting ∼20 s, and they begin in inferior colliculus (IC). We evoked three seizures in GEPRs and compared the results with those in seizure‐naive GEPRs and nonepileptic Sprague‐Dawley (SD) rats, the GEPR parent strain.

Results:Whole‐cell recording in IC slices showed that GABA‐mediated monosynaptic inhibitory postsynaptic currents (IPSCs) were reduced 55% by three brief epileptic seizures. Whole‐cell recording in IC neuronal cultures showed that currents elicited by GABA were reduced 67% by three seizures. Western blotting for the alpha1 and alpha4 subunits of the GABAAreceptor showed no statistically significant effects. In contrast, three brief epileptic seizures reduced gamma2 subunit levels by 80%.

Conclusions:The effects of the very first seizures, in animals known to be epileptic, in an area of brain known to be critical to the seizure network, were studied. The results indicate that even brief epileptic seizures can markedly reduce IPSCs and GABA currents and alter GABAA‐receptor subunit protein levels. The cause of the reductions in IPSCs and GABA currents is likely to be altered receptor subunit composition, with reduced gamma2 levels causing reduced GABAA‐receptor sensitivity to GABA. Seizure‐induced reductions in GABA‐mediated inhibition could exacerbate epilepsy.
Prevalence of Epilepsy in Bursa City Center, an Urban Area of Turkey
Authors: Çalişir Nermin , Bora Ibrahim , Irgil Emel , Boz Meral
Published: September 2006

Summary:  Purpose: The aim of this study was to determine the prevalence of epilepsy in the central district of Bursa, located in the western part of Turkey. The method used in this study was determined according to the recommendations of the World Health Organization (WHO) on prevalence research in developing countries.

Methods: In total, 2116 individuals were interviewed between September 1, 2004, and February 1, 2005. The sample group was selected from people living in the central district of Bursa, according to the stratified sampling method with regard to socioeconomic class, age, and sex. Neurology residents using standard questionnaires and semistructured interviews carried out face‐to‐face interviews.

Results: Of the 199 presumptive cases detected in the initial interview, 26 (11 female, 15 male subjects) received the diagnosis of epilepsy on the day of assessment. Prevalence of active epilepsy was 8.5 per 1000, and lifetime prevalence was 12.2 per 1000 in the central district of Bursa. Classification of the epileptic seizures revealed that 30.7% of the patients had partial and 65.3% had generalized seizures; seizures could not be classified in 3.8%. The seizures had begun during the first decade of life in 50% of the cases, and 34.6% have been using regular medications.

Conclusions: Prevalence studies in our country are scarce; thus further research including different regions and multiple centers is needed. Addition of questions suitable to the Turkish social structure to the standard questions determined by WHO may be beneficial for practitioners in considering the diagnosis of epilepsy and referring these patients to specialized centers.
Altered Tryptophan Metabolism in the Brain of Cystatin B‐Deficient Mice: A Model System for Progressive Myoclonus Epilepsy
Authors: Vaarmann Annika , Kaasik Allen , Zharkovsky Alexander
Published: September 2006

Summary:  Purpose: Progressive myoclonus epilepsy of the Unverricht–Lundborg type (EPM1) is a rare neurologic disorder, associated with mutations in the Cystatin B (Cstb) gene. Mice lacking Cstb, a cysteine protease inhibitor of the cathepsine family of proteases, provide a mammalian model for EPM1 by displaying similarly progressive ataxia, myoclonic seizures, and neurodegeneration. However, the linkage of Cstb deficit on the molecular level to pathologic features like myoclonic jerks or tonic–clonic seizures has remained unclear. We examined the tryptophan (TRP) metabolism, along the serotonin (5HT) and kynurenine (KYN) pathway in the brain of Cstb‐deficient mice, in relation to their possible involvement in the seizure phenotype.

Methods: TRP and its metabolites, along the 5HT and KYN pathways, were assayed in brain tissue by high‐pressure liquid chromatography (HPLC) with electrochemical detection. The inverted wire grid and mild handling tests were used for evaluation of ataxia and myoclonic activity.

Results: The Cstb‐deficient mice had constitutively increased TRP, 5HT, and 5‐hydroxyindole acetic acid (5HIAA) levels in the cerebral cortex and cerebellum and increased levels of KYN in the cerebellum. These neurochemical changes were accompanied with ataxia and an apparent myoclonic phenotype among the Cstb‐deficient mice.

Conclusions: Our findings suggest that secondary processes (i.e., overstimulation of serotoninergic transmission) on the cellular level, initiated by Cstb deficiency in specific brain regions, may be responsible for the myoclonic/seizure phenotype in EPM1.
Coexistence of Idiopathic Rolandic Epilepsy and CSWS in Two Families
Authors: De Tiège Xavier , Goldman Serge , Verheulpen Denis , Aeby Alec , Poznanski Nathalie , Van Bogaert Patrick
Published: September 2006

Summary:  Purpose: To report two families combining benign childhood epilepsy with centrotemporal spikes (BCECS) and cryptogenic epilepsy with continuous spike–waves during sleep (CSWS) in first‐degree relatives.

Methods: Clinical, EEG, and cerebral imaging data are described.

Results: Family 1: The proband was 3 years old at epilepsy onset. First seizures were convulsive, with centrotemporal spikes on EEG. At age 5 years, he had complex partial seizures, psychomotor regression, and centrotemporal CSWS. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) showed left parietal hypermetabolism. After several antiepileptic drug (AED) trials, valproate (VPA) and ethosuximide (ESM) induced seizure remission, CSWS disappearance, and psychomotor improvement. Learning disabilities, however, persisted. Family history was remarkable for BCECS in his father. Family 2: The proband was 2 years old at epilepsy onset. First seizures were convulsive, with centrotemporal CSWS on EEG. Despite several AED trials including corticosteroids, focal negative myoclonia, atypical absences, and psychomotor regression occurred, leading to severe mental retardation. FDG‐PET showed bilateral parietal hypermetabolism. Vagus nerve stimulator was implanted. Her family history was remarkable for BCECS in her father and febrile convulsions in infancy in her mother.

Conclusions: These data suggest the existence of a common genetic basis between BCECS and cryptogenic epilepsies with CSWS. The higher expression in patients with CSWS could be related to other genetic or acquired factors. These data suggest that these epileptic syndromes constitute edges of a continuum.
Exacerbation of Seizures in Medial Temporal Lobe Epilepsy Due to an α1‐Adrenergic Antagonist
Authors: Iváñez Vicente , Ojeda Joaquín
Published: September 2006

Summary: Purpose:We describe the first reported case of a proconvulsant effect of an α1‐adrenergic antagonist in humans.

Methods:A patient with medial temporal lobe seizures (MTLE) had increased seizure frequency after treatment with tamsulosin, an α1‐adrenergic antagonist.

Results:Experimental evidence suggests that noradrenaline, which has inhibitory effects on the excitatory synaptic response, can act as a powerful anticonvulsant. Mostly, α2‐adrenoreceptors, but also α1‐adrenoreceptors, have been implicated in this effect by different experimental models. Clinical reports of a proconvulsant or anticonvulsant effect of drugs that act through the adrenergic pathway are scarce.

Conclusions:This is the first report of a proconvulsant effect by an α1‐adrenergic antagonist in humans and suggests that α1‐adrenoreceptors may be involved in modulating noradrenergic activity in the limbic region.
Orgasm‐induced Seizures: A Study of Six Patients
Authors: Ozkara Cigdem , Ozdemir Samuray , Yılmaz Aynur , Uzan Mustafa , Yeni Naz , Ozmen Mine
Published: September 2006

Summary: Purpose:Reflex seizures are known as the epileptic seizures triggered by some specific stimuli in sensitive patients. They are often classified according to the stimuli that trigger them rather than by the type of the seizure. Epileptic seizures induced by sexual orgasm are very rare in the literature.

Methods:We report six patients with different epileptic syndromes who experienced seizures after sexual intercourse and orgasm.

Results:All patients are women whose epileptogenic focus was in the right temporal in four and left frontal in one patient. One patient had pure generalized reflex epilepsy.

Conclusions:Seizures induced by orgasm are very rare, with female and right hemisphere dominance requiring complex mechanisms to occur.
Neuromagnetic Source Localization of Epileptiform Activity in Patients with Graphogenic Epilepsy
Authors: Tanaka Naoaki , Sakurai Kotaro , Kamada Kyousuke , Takeuchi Fumiya , Takeda Youji , Koyama Tsukasa
Published: September 2006

Summary:  Purpose: To clarify the source localization of epileptiform activity by using magnetoencephalography (MEG) in patients with graphogenic epilepsy.

Methods: MEG and simultaneous EEG were recorded with a 204‐channel whole‐head MEG system in two patients with graphogenic epilepsy. During the MEG recordings, the patients performed a set of tasks comprising mental arithmetic calculation, speaking, moving the right arm in a manner resembling writing, writing, and thinking of writing. Equivalent current dipoles (ECD) were calculated for epileptiform discharges on MEG by using a single‐dipole model. The ECD were superimposed on the magnetic resonance images of the patients.

Results: The task of writing provoked seizures, in which both patients jerked the right arms. Thinking of writing also induced these seizures. In both patients, EEG associated with the seizures showed bursts of spike‐and‐slow‐wave complexes predominantly in the centroparietal region. MEG also showed epileptiform discharges corresponding to the EEG bursts. ECDs obtained from the discharges were clustered in the left centroparietal area.

Conclusions: Thinking of writing was a trigger for the seizures, as well as the task of writing. The source of the epileptiform discharge associated with the seizures was localized in the unilateral centroparietal area. The findings suggest that the centroparietal region plays an important role in the pathophysiology underlying these two graphogenic epilepsy cases.
Use of Selective Serotonin Reuptake Inhibitors and Sleep Disturbances in Community‐Dwelling Older Women
Authors: Ensrud Kristine E. , Blackwell Terri L. , Ancoli‐Israel Sonia , Redline Susan , Yaffe Kristine , Diem Susan , Claman David , Stone Katie L. ,   for the Study of Osteoporotic Fractures Research Group
Published: September 2006

OBJECTIVES: To determine the association between use of selective serotonin reuptake inhibitors (SSRIs) and objective measures of sleep disturbances in older community‐dwelling women, including women without evidence of depression.

DESIGN: Cross‐sectional study.

SETTING: Four U.S. clinical centers.

PARTICIPANTS: Two thousand eight hundred fifty‐three women aged 71 and older (2,630 nonusers of antidepressants and 223 taking SSRIs alone, not in combination with other antidepressants).

MEASUREMENTS: Medication use, assessed using an interviewer‐administered questionnaire with verification of use from medication containers and computerized dictionary used to categorize type of medication; evidence of depression assessed using self‐report or a score of 6 or higher on the Geriatric Depression Scale; and sleep parameters measured using a wrist actigraph, with data collected for an average of four consecutive 24‐hour periods.

RESULTS: Of the overall cohort of 2,853 women and of 2,337 women without evidence of depression, sleep disturbances were more common in women taking SSRIs than in those not taking antidepressants. After excluding women with evidence of depression and adjusting for multiple potential confounders, women taking SSRIs were more likely to have a sleep duration of 5 hours or less (multivariate odds ratio (MOR)=2.15, 95% confidence interval (CI)=1.04–4.47), sleep efficiency less than 70% (MOR=2.37, 95% CI=1.32–4.25), sleep latency of 1 hour or more (MOR=3.99, 95% CI=2.29–6.96) and eight or more long wake episodes (MOR=1.75, 95% CI=0.99–3.10).

CONCLUSION: SSRI use by older women, including those without evidence of depression, is associated with a greater likelihood of sleep disturbances, including poorer sleep efficiency, longer sleep latency, and sleep fragmentation, manifested by multiple long wake episodes. These results add to the uncertainty regarding risks and benefits of SSRI use in aged populations.