bluuebunny/crossref_metadata_2025 huggingface dataset:
Alopecia in association with severe seborrhoeic dermatitis following combination antiretroviral therapy for acute retroviral syndrome
Authors: Hardcastle NJ , Tunbridge AJ , Shum KW , Dockrell DH , Green ST
Published: August 2005

We present a case where alopecia occurred with severe seborrhoeic dermatitis associated with the commencement of combination antiretroviral therapy for acute retroviral syndrome. We postulate that the eruption could represent a novel manifestation in association with immunological response to antiretroviral therapy.
Synchronous balneophototherapy is effective for the different clinical types of psoriasis
Authors: Holló P , Gonzalez R , Kása M , Horváth A
Published: August 2005

Background  The efficacy of synchronous balneophototherapy in clearing psoriasis is based on the multiple‐targeted effects of UVB light and Dead Sea salt. Their synchronous application produces a synergic effect.

Objective  The purpose of this retrospective study is: 1) to evaluate the efficacy of synchronous balneophototherapy for treating different clinical types of psoriasis; 2) to determine whether there is any difference between response to treatment, and 3) to gain more data in order to predict the effect of treatment in different clinical types, and thus to support the selection of patients for treatment.

Methods  Patients received a basic course of synchronous balneophototherapy according to the Regensburg scheme, consisting of 35 treatment sessions, followed by a maintenance course of a further 25 treatments. The patients’ skin status was monitored by weekly assessment using the PASI score throughout the course. The efficacy of the treatment was evaluated through the results of 373 patients treated according to protocol during the basic course, and the results of 78 of these patients during the maintenance course. One hundred and eighty‐six patients were enrolled into the study comparing the efficacy of the basic course for the different clinical types of psoriasis: data of patients with large plaques, small plaques, guttate and confluating type of skin signs were summarized and compared.

Results  During the basic course of treatment 70.7% improvement of the average PASI index was observed; the average PASI index decreased from 16.14 to 4.73. A further improvement from 4.58 to 4.27 of the average PASI was found during the maintenance therapy. Small plaque‐type skin signs showed the best response with a PASI decrease of 76.1%; Guttate type had a PASI decrease of 73.7%, large plaque type, 67.1% and confluating type, 62%. Comparing data with the average PASI decrease, a statistically significant lower decrease was found in confluating type cases.

Conclusions  These results confirm that synchronous balneophototherapy is an effective treatment modality for different clinical types of psoriasis. Patients with small plaques have the greatest chance of the most marked clinical clearing; guttate and large plaque types of psoriasis also respond well to the treatment.
Correlation between HLA and pityriasis rosea susceptibility in Brazilian blacks
Authors: Miranda SMB , Porto LC , Pontes LFS , Filgueira AL
Published: August 2005

Objectives  The human leucocyte antigen (HLA) has been related to susceptibility factors in several diseases. This study aimed to determine the potential genetic susceptibility of patients with pityriasis rosea (PR) through HLA molecular typing analysis.

Methods  The method of choice was polymerase chain reaction with sequence‐specific primers (PCR‐SSP) using low‐resolution typing kits, with determination of the alleles class I (HLA‐A, HLA‐B and HLA‐C) and class II (HLA‐DRB1, DRB3, DRB4, DRB5 and DQB1) performed in 30 Afro‐Brazilian PR‐diagnosed patients and 45 healthy individuals as the control group (PR‐C).

Results  Analysis of the HLA typing results showed that the relative risk (RR) of 4.00 [95% confidence interval (95% CI) 1.20–13.28, two‐tailed P = 0.018] for allele HLA‐DQB1*04 class II, detected in 33.3% of PR patients, was significant. By contrast, in the control group only 11.1% of subjects had that allele. Three out of six B*51 alleles and three out of six B*53 alleles detected in PR patients were found, together with the allele DQB1*04.

Conclusion  We suggest that alleles DQB1*04 may be involved in the genetic susceptibility of PR based on the significant predominance of those alleles observed in the black PR patients. We also recommend that more studies are conducted on populations of other ethnic origins, preferentially with higher resolution techniques of DNA typing.
Ego involvement and effort: Cardiovascular, electrodermal, and performance effects
Authors: Gendolla Guido H. E. , Richter Michael
Published: September 2005

An experiment with N=52 university students manipulated ego involvement (low vs. high) and task difficulty (unfixed vs. easy) of a letter detection task. In accordance with the theoretical predictions about the role of ego involvement in active coping, high ego involvement increased the performance‐related reactivity of systolic blood pressure, diastolic blood pressure, heart rate, and also the number of unspecific skin conductance responses when task difficulty was unfixed (“do your best”). Ego involvement had no impact on autonomic reactivity when task difficulty was easy due to a fixed low performance standard. Furthermore, participants in the ego involvement/unfixed condition, where autonomic reactivity was relatively strong, committed significantly fewer errors in the letter detection task than those in the other conditions, reflecting an association between mental effort and performance.
Reduced prepulse inhibition in unaffected siblings of schizophrenia patients
Authors: Kumari Veena , Das Mrigen , Zachariah Elizabeth , Ettinger Ulrich , Sharma Tonmoy
Published: September 2005

We investigated whether prepulse inhibition of the startle response is reduced in siblings of schizophrenia patients compared to age‐ and sex‐matched healthy controls. Nineteen unaffected biological siblings and 19 controls were assessed on prepulse inhibition by monaural and binaural acoustic prepulse stimuli, with the startle stimuli always presented binaurally. There was significantly less prepulse inhibition in siblings, compared to controls, with binaural prepulse stimuli, as also seen previously in schizophrenia patients. The difference between siblings and controls in prepulse inhibition with the left or right ear prepulse stimuli was not significant because of a pronounced increase in prepulse inhibition with monaural, relative to binaural, prepulses in the sibling group. High schizotypal ratings were mildly associated with reduced prepulse inhibition. Prepulse inhibition may provide a useful measure in the search for schizophrenia genes.
Respiratory sinus arrhythmia predicts written disclosure outcome
Authors: Sloan Denise M. , Epstein Eva M.
Published: September 2005

Research has indicated that writing about traumatic experiences is associated with beneficial health effects compared with writing about emotionally neutral topics. What remains unclear are those factors that moderate the beneficial effects associated with written disclosure. This study examined respiratory sinus arrhythmia (RSA) as a moderator of written disclosure outcome. Findings indicated that individuals with the highest RSA during the first written disclosure session benefited most from written disclosure in terms of physical health complaints and depression symptoms. As expected, RSA did not impact outcome for participants assigned to a control condition. These findings indicate that individuals who display good emotion regulation skills are best served by written disclosure.
Food shopping behaviour in Scotland: the influence of relative rurality
Authors: McEachern Morven G. , Warnaby Gary
Published: September 2005

Despite a number of studies investigating consumer food purchase behaviour, few studies actually address the nature of the rural consumer. This may have implications for the generalization of much research on food purchase behaviour, as official estimates of the UK rural population vary between 8.5% and 24%. This paper compares and contrasts the food shopping behaviour of customers in rural and urban areas in Scotland. Particular focus is given on respondent characteristics, attitudes towards rural and urban locations, distance travelled for food shopping purposes and store patronage. Results from the research emphasize the notion that rural and urban retailing should be conceptualized as a continuum rather than being regarded as dichotomous, and a conceptual framework is proposed.
A Measure of Trust in Insurers
Authors: Goold Susan Dorr , Fessler David , Moyer Cheryl A.
Published: September 2005

Background. Patient‐centered assessments are increasingly important. Patients repeatedly emphasize the importance of trust in health care institutions and personnel.

Objectives. (1) Develop a conceptual framework for trust in health care organizations and a comprehensive, reliable measure of trust in health insurers. (2) Examine predictors and correlates of trust in insurers.

Study Design. A conceptual framework for trust in health organizations based on theory and empirical studies was used to develop items for a structured telephone survey, which also included measures of health and utilization, doctor–patient trust, and satisfaction with care. Principal components factor analyses identified hypothesized domains of trust in health insurers and identified items for scales. Internal consistency assessment used Cronbach's α. Univariate analyses used Pearson's r or Student's t‐tests.

Sample. Insured residents of Southeastern Michigan (n=400).

Results. Respondents were diverse in age, gender, ethnicity, health, and socioeconomic status. One dominant factor (eigenvalue>10) included hypothesized domains: administrative competence, clinical competence, advocacy and beneficence, fairness, honesty and openness, and one global item. Multidimensional scales were reliable (long version 13 items, α=0.95, short: 9 items, α=0.91). Insurer trust correlated strongly with trust in doctors (r=0.49 and 0.46) and satisfaction with care (r=0.70 and 0.66), and with an item assessing overall worry about health insurance (r=−0.37 and −0.35). Those with less trust in their insurer were more likely to say that they would change insurance plans (p<.001).

Conclusions. This well‐grounded, reliable measure of enrollee trust in insurers can be a useful patient‐centered assessment tool.
Delayed Care and Unmet Needs among Health Care System Users: When Does Fiduciary Trust in a Physician Matter?
Authors: Mollborn Stefanie , Stepanikova Irena , Cook Karen S.
Published: September 2005

Objectives.To examine whether fiduciary trust in a physician is related to unmet health care needs and delayed care among patients who have a regular physician, and to investigate whether the relationships between trust and unmet health care needs and delays in care are attenuated for disadvantaged patients who face structural obstacles to obtaining health care.

Data Sources/Study Setting.The 1998–1999 Community Tracking Study (CTS) Household Survey, a cross‐sectional sample representative of the U.S. noninstitutionalized population. This study analyzes adults who usually see the same physician for their health care (n=29,994).

Study Design.We estimated logistic regression models of the association of trust with unmet health care needs and delayed care. We tested interactions between trust and barriers to obtaining care, including minority race/ethnicity, poverty, and the absence of health insurance. Control variables included patients' sociodemographic characteristics, health status, satisfaction with the available choice of primary physicians, and the number of physician visits during the last year.

Principal Findings.Patients' fiduciary trust in a physician is negatively associated with the likelihood of reporting delayed care and unmet health care needs among most patients. Among African Americans, Hispanics, the poor, and the uninsured, however, fiduciary trust is not significantly associated with the likelihood of delayed care. For unmet needs, only the uninsured have no significant association with trust.

Conclusions.Results show that trust is associated with improved chances of getting needed care across most subgroups of the population, although this relationship varies by subpopulation.
Effects of Cattle Grazing on Diversity in Ephemeral Wetlands
Authors: MARTY JAYMEE T.
Published: September 2005

Abstract:  Cattle are usually thought of as a threat to biodiversity. In regions threatened by exotic species invasion and lacking native wild grazers, however, cattle may produce the type of disturbance that helps maintain diverse communities. Across 72 vernal pools, I examined the effect of different grazing treatments (ungrazed, continuously grazed, wet‐season grazed and dry‐season grazed) on vernal‐pool plant and aquatic faunal diversity in the Central Valley of California. After 3 years of treatment, ungrazed pools had 88% higher cover of exotic annual grasses and 47% lower relative cover of native species than pools grazed at historical levels (continuously grazed). Species richness of native plants declined by 25% and aquatic invertebrate richness was 28% lower in the ungrazed compared with the continuously grazed treatments. Release from grazing reduced pool inundation period by 50 to 80%, making it difficult for some vernal‐pool endemic species to complete their life cycle. My results show that one should not assume livestock and ranching operations are necessarily damaging to native communities. In my central California study site, grazing helped maintain native plant and aquatic diversity in vernal pools.
Recovery of Soil Macrofauna Communities after Forest Clearance in Eastern Amazonia, Brazil
Authors: MATHIEU J. , ROSSI J.‐P. , MORA P. , LAVELLE P. , MARTINS P. F. da S. , ROULAND C. , GRIMALDI M.
Published: September 2005

Abstract: As primary forest is cleared, pastures and secondary forest occupy an increasing space in the Amazonian landscape. We evaluated the effect of forest clearing on a soil macrofauna (invertebrate) community in a smallholder farming system of southeastern Amazonia. We sampled the soil macrofauna in 22 plots of forest, upland rice fields, pastures, and fallows of different ages. In total, we collected 10,728 invertebrates. In cleared plots the species richness per plot of the soil macrofauna fell from 76 to 30 species per plot immediately after forest clearance, and the composition of the new community was different. Ants, termites, and spiders were most affected by the disturbance. In plots deforested several years before, the effect of forest clearance was highly dependent on the type of land use (pasture or fallow). In fallows, the community was similar to the initial state. The species richness per plot in old fallows rose to 66, and the composition was closer to the primary forests than to the other types of land use. On the contrary, in the pastures the species richness per plot remained low at 47. In fallows, all the groups showed a richness close to that in primary forest, whereas in the forest only the richness of earthworms and Coleoptera recovered. Our results show that forest clearing constitutes a major disturbance for the soil macrofauna and that the recovery potential of the soil macrofauna after 6 or 7 years is much higher in fallows than in pastures. Thus, fallows may play a crucial role in the conservation of soil macrofauna.
Using Vascular Plants as a Surrogate Taxon to Maximize Fungal Species Richness in Reserve Design
Authors: CHIARUCCI ALESSANDRO , D'AURIA FRANCESCA , DE DOMINICIS VINCENZO , LAGANÀ ANGELA , PERINI CLAUDIA , SALERNI ELENA
Published: September 2005

Abstract:  Fungi are a hyperdiverse taxonomic group that may be disappearing at a very high rate. Identifying fungal species is difficult in the field, and the use of highly specialized taxonomists is required. Data and expertise on vascular plants are, on the other hand, much more common and easy to find. We tested the potential of using vascular plants as surrogates to select reserve sites that maximize the pooled number of fungal species. We used data from 25 forest plots in Tuscany, Italy, that were sampled for woody plants, all other plants, and fungi. Species richness of woody plants and all other plants did not correlate with species richness of fungi. The gradients in species composition were similar among the three considered groups, as indicated by a detrended correspondence analysis ordination and species complementarity between pairs of plots. Fungal communities of the 25 plots had a lower β diversity than plant communities, and there were no pairs of totally complementary sites. Site prioritization for conservation was obtained through integer linear programming to find for any given number of sites those combinations containing the maximum pooled species richness of woody plants or all plants. The combinations of sites obtained by optimizing vascular plant species did not maximize the pooled species richness of fungi, whereas those obtained by maximizing woody plant species provided better results for sets of four to eight plots, but not for all the possible combinations. These results indicated that, in general, vascular plants cannot be used to maximize fungal species richness.
Intellectual Prognosis of Status Epilepticus in Adult Epilepsy Patients: Analysis with Wechsler Adult Intelligence Scale–Revised
Authors: Adachi Naoto , Kanemoto Kousuke , Muramatsu Reimi , Kato Masaaki , Akanuma Nozomi , Ito Masumi , Kawasaki Jun , Onuma Teiichi
Published: September 2005

Summary:  Purpose: Status epilepticus (SE) appears to cause cognitive dysfunction as well as other serious neurologic sequelae. To confirm whether SE produces a subsequent intellectual decline, we evaluated intellectual function prospectively in adult epilepsy patients with and without SE.

Methods: Of 1,685 patients with epilepsy who underwent comprehensive neuropsychological testing in two national hospitals in Japan, 15 patients experienced an episode of SE afterward and underwent the second neuropsychological examination after the SE episode. Forty clinically matched patients with epilepsy, but without an episode of SE since their initial neuropsychological examination, were also reevaluated. We compared IQs and subscores from the Wechsler Adult Intelligence Scale–Revised between the two groups by repeated measures analysis of variance. In the patients who experienced an SE episode, SE‐related variables (i.e., age at the SE episode and type and duration of SE) and epilepsy‐related variables such as epilepsy type, lateralization of EEG abnormalities, the presence of mesial temporal sclerosis, and previous history of SE, were evaluated in relation to intellectual outcome.

Results: Patients with SE, in comparison to those without SE, failed to show any significant post‐SE intellectual decline. Furthermore, neither the SE‐related variables nor the clinical characteristics were correlated with intellectual outcome.

Conclusions: Our findings suggest that SE does not lead to a significant intellectual decline in adult patients receiving treatment for epilepsy.
Localizing Value of Ictal–Interictal SPECT Analyzed by SPM (ISAS)
Authors: McNally Kelly A. , Paige A. LeBron , Varghese George , Zhang Heping , Novotny Edward J. , Spencer Susan S. , Zubal I. George , Blumenfeld Hal
Published: September 2005

Summary:  Purpose: The goal of neuroimaging in epilepsy is to localize the region of seizure onset. Single‐photon emission computed tomography with tracer injection during seizures (ictal SPECT) is a promising tool for localizing seizures. However, much uncertainty exists about how to interpret late injections, or injections done after seizure end (postictal SPECT). A widely available and objective method is needed to interpret ambiguous ictal and postictal scans, with changes in multiple brain regions.

Methods: Ictal or postictal SPECT scans were performed by using [99mTc]‐labeled hexamethyl‐propylene‐amine‐oxime (HMPAO), and images were analyzed by comparison with interictal scans for each patient. Forty‐seven cases of localized epilepsy were studied. We used methods that can be implemented anywhere, based on freely downloadable software and normal SPECT databases (http://spect.yale.edu). Statistical parametric mapping (SPM) was used to localize a single region of seizure onset based on ictal (or postictal) versus interictal difference images for each patient. We refer to this method as ictal–interictal SPECT analyzed by SPM (ISAS).

Results: With this approach, ictal SPECT identified a single unambiguous region of seizure onset in 71% of mesial temporal and 83% of neocortical epilepsy cases, even with late injections, and the localization was correct in all (100%) cases. Postictal SPECT, conversely, with injections performed soon after seizures, was very poor at localizing a single region based on either perfusion increases or decreases, often because changes were similar in multiple brain regions. However, measuring which hemisphere overall had more decreased perfusion with postictal SPECT, lateralized seizure onset to the correct side in ∼80% of cases.

Conclusions: ISAS provides a validated and readily available method for epilepsy SPECT analysis and interpretation. The results also emphasize the need to obtain SPECT injections during seizures to achieve unambiguous localization.
Ethinyl Estradiol, Not Progestogens, Reduces Lamotrigine Serum Concentrations
Authors: Reimers Arne , Helde Grethe , Brodtkorb Eylert
Published: September 2005

Summary:  Purpose: To study the interaction between lamotrigine (LTG) and hormonal contraception.

Methods: LTG serum concentrations of female patients using either no hormonal contraception (n = 18), an ethinyl estradiol (EE)‐containing (n = 11), or a progestogen (PG)‐only–containing compound (n = 16) were analyzed. Patients were recruited prospectively, and blood samples were drawn during drug fasting and at steady‐state conditions. Comedication with enzyme inducers, valproate, topiramate, or sertraline was not allowed. Some patients changed groups and thus served as their own controls. Samples were analyzed by a gas chromatography/ mass spectroscopy method. The Mann–Whitney U test was used for statistical comparison of the groups.

Results: The LTG serum concentration‐to‐dose ratio (CDR), expressed as (mg/L)/(mg/d) was significantly lower in women using EE than in the control group (mean ± SD, 0.010 ± 0.004 vs. 0.017 ± 0.006; p = 0.003). The CDR in women using PG was 0.02 ± 0.007, which was not statistically different from controls. No difference was found in CDR between women using either oral, topical, or parenteral PG. Five women switched from the control to the EE group and experienced a considerable reduction in CDR. An increase of the CDR toward control level was seen in the two women who changed from EE to PG.

Conclusions: It is the EE component of oral contraceptives that interacts with LTG. The PG‐only compounds did not alter LTG serum concentrations in this study. These findings should be considered when counselling women with epilepsy in the childbearing ages.
Increased Expression of Ferritin, an Iron‐storage Protein, in Specific Regions of the Parahippocampal Cortex of Epileptic Rats
Authors: Gorter Jan A. , Mesquita Ana R.M. , Van Vliet Erwin A. , Da Silva Fernando H. Lopes , Aronica Eleonora
Published: September 2005

Summary:  Purpose: Iron accumulation in the brain has been associated with neurodegenerative disorders, including epilepsy. In our previous SAGE study, we showed that ferritin, an iron‐storage protein, was one of the genes (Ferritin‐H) that showed overexpression before the chronic epileptic phase. In this study we used ferritin as indicator for disturbed iron homeostasis to acquire insight into whether this could play a role in the pathogenesis of temporal lobe epilepsy.

Methods: With immunocytochemistry, we studied the regional and cellular distribution of ferritin protein in an animal model for temporal lobe epilepsy in which spontaneous seizures develop a few weeks after electrically induced status epilepticus (SE).

Results: Increased ferritin expression was observed in regions known to be vulnerable to cell death, mainly in reactive microglial cells of epileptic rats. Ferritin expression after SE was initially high, especially throughout the hippocampus, but decreased over time. In the chronic epileptic phase, it was still upregulated in regions where extensive cell loss occurs during the early acute and latent period. Within the parahippocampal region, the most persistent ferritin overexpression was present in microglial cells in layer III of the medial entorhinal area. The upregulation was most extensive in rats that had developed a progressive form of epilepsy with frequent seizures (approximately five to 10 seizures per day).

Conclusions: The fact that ferritin upregulation is still present in specific limbic regions in chronic epileptic rats, when neuronal loss is absent or minimal, suggests a role of iron in the pathogenesis and progression of epilepsy.
Characteristics of Male Veterans with Psychogenic Nonepileptic Seizures
Authors: Dworetzky Barbara A. , Strahonja‐Packard Andreja , Shanahan Christopher W. , Paz Jeanette , Schauble Barbara , Bromfield Edward B.
Published: September 2005

Summary:  Purpose: To describe male patients (pts) with psychogenic nonepileptic seizures (PNESs) followed up in a Veteran's Administration (VA) seizure clinic and to compare them with those with epileptic seizures (ESs) by using clinical, and psychosocial variables.

Methods: Adult male veterans seen between 1997 and 2000 with ESs were compared with those with PNESs with respect to clinical history (head trauma, antiepileptic drug exposure, depression, anxiety, substance abuse, seizure description), documented chronic pain, posttraumatic stress disorder (PTSD), compensation for diagnosis, neurologic examination, and test results including imaging and EEG data.

Results: Men with PNESs were younger and reported more frequent events, and diagnoses of chronic pain, anxiety, and PTSD were significantly greater. Neuroimaging [computed tomography (CT) or magnetic resonance imaging (MRI) of the brain] and neurologic examination were significantly more likely to be normal or nonspecific in pts with PNESs, although history of ictal urinary incontinence or service‐connected compensation for diagnosis did not distinguish the groups.

Conclusions: Male veterans with PNESs have characteristics similar to those reported in the literature, even though younger women have dominated previously studied populations. Compared with men with ESs, those with PNESs are more likely to have chronic pain, anxiety, and PTSD, as well as normal examinations and brain imaging.
Characterizing Magnetoencephalographic Spike Sources in Children with Tuberous Sclerosis Complex
Authors: Iida Koji , Otsubo Hiroshi , Mohamed Ismail S. , Okuda Chiyuki , Ochi Ayako , Weiss Shelly K. , Chuang Sylvester H. , Snead O. Carter
Published: September 2005

Summary:  Purpose: Tuberous sclerosis complex (TSC) often causes medically intractable seizures. Magnetoencephalography (MEG) localizes epileptiform discharges. To evaluate the use of MEG spike sources (MEGSSs) for localizing epileptic zones in TSC patients, we characterized MEGSSs and correlated them to EEG and magnetic resonance imaging (MRI) results.

Methods: We analyzed data from seven children who underwent prolonged video‐EEG, MEG, and MRI. We classified MEGSSs as clusters (six or more spike sources, ≤1 cm between sources) and scatters (fewer than six spike sources regardless of distance between sources; sources with >1 cm between sources regardless of number of sources).

Results: A single, unilateral cluster with additional scatters occurred in two patients; these predominantly lateralized dipoles correlated to prominent tubers on MRI and ictal/interictal EEG zones. Bilateral clusters with scatters existed in two patients; cluster locations partly overlapped multiple prominent tubers. These patients also had bilateral or diffuse interictal discharges, bilateral or generalized seizures, and changing seizure types and EEG findings. Only bilateral scatters occurred in three patients; scatters partly overlapped EEG interictal/ictal‐onset regions; one patient had coexisting generalized seizures. In one patient with equally bilateral scatters, scatters overlapped a prominent tuber and interictal/ictal‐onset zones in the right frontal region.

Conclusions: MEG contributes to information from EEG and MRI for localizing epileptogenic zones in children with TSC. A single cluster with scatters in a unilateral hemisphere predicts a primary epileptogenic zone or hemisphere; bilateral or multiple clusters indicate bilateral primary or potential epileptogenic zones; and bilateral scatters without clusters may indicate epileptogenic zones that are hidden within extensive areas of scattered MEGSSs.
Pregabalin Drug Interaction Studies: Lack of Effect on the Pharmacokinetics of Carbamazepine, Phenytoin, Lamotrigine, and Valproate in Patients with Partial Epilepsy
Authors: Brodie Martin J. , Wilson Elaine A. , Wesche David L. , Alvey Christine W. , Randinitis Edward J. , Posvar Edward L. , Hounslow Neil J. , Bron Nicola J. , Gibson G. L. , Bockbrader Howard N.
Published: September 2005

Summary:  Purpose: Pregabalin (PGB) is an α2‐δ ligand with demonstrated efficacy in epilepsy, neuropathic pain, and anxiety disorders. PGB is highly efficacious as adjunctive therapy in patients with refractory partial seizures.

Methods: Given its efficacy as adjunctive therapy, the potential for interaction of PGB with other antiepileptic drugs (AEDs) was assessed in patients with partial epilepsy in open‐label, multiple‐dose studies. Patients received PGB, 600 mg/day (200 mg q8h) for 7 days, in combination with their individualized maintenance monotherapy with valproate (VPA), phenytoin (PHT), lamotrigine (LTG), or carbamazepine (CBZ).

Results: Trough steady‐state concentrations of CBZ (and its epoxide metabolite), PHT, LTG, and VPA were unaffected by concomitant PGB administration. Likewise, PGB steady‐state pharmacokinetic parameter values were similar among patients receiving CBZ, PHT, LTG, or VPA and, in general, were similar to those observed historically in healthy subjects receiving PGB alone. The PGB–AED combinations were generally well tolerated. PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug–drug interactions.
Modulation of CaM Kinase II Activity Is Coincident with Induction of Status Epilepticus in the Rat Pilocarpine Model
Authors: Singleton Michael W. , Holbert William H. , Lee Anh Tuyet , Bracey James M. , Churn Severn B.
Published: September 2005

Summary:  Purpose: This study was conducted to characterize the early cellular changes in CaM kinase II activity that occur during the induction of status epilepticus (SE).

Methods: The pilocarpine model of SE was characterized both behaviorally and electrographically. At specific time points after the first discrete seizure, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II–specific substrate, autocamtide III, was used to determine kinase activity.

Results: After the development of SE, the data show an immediate inhibition of both cortical and hippocampal CaM kinase II activity in homogenate, but a delayed inhibition in synaptic kinase activity. The maintenance of synaptic kinase activity was due to a translocation of CaM kinase II protein to the synapse. However, despite the translocation of functional kinase, CaM kinase II activity was not maintained, membrane potential was not restored, and the newly translocated CaM kinase II did not terminate the SE event. Unlike the homogenate samples, in the crude synaptoplasmic membrane (SPM) subcellular fractions, a positive correlation is found between the duration of SE and the inhibition of CaM kinase II activity in both the cortex and hippocampus.

Conclusions: The data support the hypothesis that alterations of CaM kinase II activity are involved in the early events of SE pathology.
Photic‐ and Pattern‐induced Seizures: Expert Consensus of the Epilepsy Foundation of America Working Group
Authors: Harding Graham , Wilkins Arnold J. , Erba Giuseppe , Barkley Gregory L. , Fisher Robert S.
Published: September 2005

Summary:  Purpose: In August, 2004, the Epilepsy Foundation of America convened a workshop to begin to develop an expert consensus on photosensitive seizures.

Methods: Literature and data were reviewed, and consensus was derived from discussion.

Results: A flash is a potential hazard if it has luminance ≥20 cd/m2, occurs at a frequency of ≥3 Hz, and occupies a solid visual angle of ≥0.006 steradians (∼10% of the central visual field or 25% of screen area at typical viewing distances). A transition to or from saturated red also is considered a risk. A pattern with the potential for provoking seizures contains clearly discernible stripes, numbering more than five light–dark pairs of stripes in any orientation. When the light–dark stripes of any pattern collectively subtend at the eye from the minimal‐expected viewing distance a solid angle of >0.006 steradians, the luminance of the lightest stripe is >50 cd/m2, and the pattern is presented for ≥0.5 s, then the pattern should display no more than five light–dark pairs of stripes, if the stripes change direction, oscillate, flash, or reverse in contrast; if the pattern is unchanging or smoothly drifting in one direction, no more than eight stripes. These principles are easier to apply in the case of fixed media, for example, a prerecorded TV show, which can be analyzed frame‐by‐frame, as compared with interactive media.

Conclusions: A consensus view of stimuli likely to provoke visually evoked seizures can be developed.
Predicting Posttraumatic Epilepsy with MRI: Prospective Longitudinal Morphologic Study in Adults
Authors: Messori Anna , Polonara Gabriele , Carle Flavia , Gesuita Rosaria , Salvolini Ugo
Published: September 2005

Summary: Purpose:Evaluation of morphologic risk factors for posttraumatic epilepsy (PTE) by using brain magnetic resonance imaging (MRI) in serial assessments ≤2 years after traumatic brain injury (TBI).

Methods:Brain MRI hyperintense (gliosis) or hypointense (hemosiderin) areas or both were assessed in the images of 135 adult TBI inpatients who completed a 2‐year clinical, EEG, and MRI study protocol. Overall clinical follow‐up for the development of PTE was 5–10 years (median, 102 months). Morphologic risk factors for PTE were evaluated by using Kaplan–Meier curves and Cox regression analysis.

Results:In 20 patients, PTE developed. Kaplan–Meier curves showed that gliomesenchymal sequelae of focal brain lesions (subdural hematomas/contusions) that required surgical treatment (sSDH‐C) were a PTE risk factor (p < 0.001), as were sequelae of nonsurgical hemorrhagic contusions with gliosis wall incompletely surrounding hemosiderin dregs (IW) (p = 0.039) and mainly those with time‐related changes from incomplete to complete gliosis wall around hemosiderin (I/CW) (p = 0.005); those with early hemosiderin completely surrounded by gliosis (CW) were not (p = 0.821). Cox regression analysis showed that for patients with sequelae of sSDH‐C, the PTE risk was 4.38 (p = 0.023) times higher than for those who did not require surgical treatment or underwent surgery because of purely extradural hematoma; for those with IW and I/CW lesions, considered pooled, it was 6.61 times higher (p = 0.014) than for those with CW lesions.

Conclusions:MRI follow‐up examination in the early chronic stage can differentiate among low‐, intermediate‐, and high‐risk sequelae of TBI. These findings yield new evidence for, but do not resolve, the debate on posttraumatic epileptogenesis.
Cerebral Damage in Epilepsy: A Population‐based Longitudinal Quantitative MRI Study
Authors: Liu Rebecca S. N. , Lemieux Louis , Bell Gail S. , Sisodiya Sanjay M. , Bartlett Philippa A. , Shorvon Simon D. , Sander Josemir W. A. S. , Duncan John S.
Published: September 2005

Summary:  Purpose: Whether cerebral damage results from epileptic seizures remains a contentious issue. We report on the first longitudinal community‐based quantitative magnetic resonance imaging (MRI) study to investigate the effect of seizures on the hippocampus, cerebellum, and neocortex.

Methods: One hundred seventy‐nine patients with epilepsy (66 temporal lobe epilepsy, 51 extratemporal partial epilepsy, and 62 generalized epilepsy) and 90 control subjects underwent two MRI brain scans 3.5 years apart. Automated and manual measurement techniques identified changes in global and regional brain volumes and hippocampal T2 relaxation times.

Results: Baseline hippocampal volumes were significantly reduced in patients with temporal lobe epilepsy and could be attributed to an antecedent neurologic insult. Rates of hippocampal, cerebral, and cerebellar atrophy were not syndrome specific and were similar in control and patient groups. Global and regional brain atrophy was determined primarily by age. A prior neurologic insult was associated with reduced hippocampal and cerebellar volumes and an increased rate of cerebellar atrophy. Significant atrophy of the hippocampus, neocortex, or cerebellum occurred in 17% of patients compared with 6.7% of control subjects. Patients with and without significant volume reduction were comparable in terms of seizure frequency, antiepileptic drug (AED) use, and epilepsy duration, with no identifiable risk factors for the development of atrophy.

Conclusions: Overt structural cerebral damage is not an inevitable consequence of epileptic seizures. In general, brain volume reduction in epilepsy is the cumulative effect of an initial precipitating injury and age‐related cerebral atrophy. Significant atrophy developed in individual patients, particularly those with temporal lobe and generalized epilepsy. Longer periods of observation may detect more subtle effects of seizures.
Hemispherectomy for Catastrophic Epilepsy in Infants
Authors: González‐Martínez Jorge A. , Gupta Ajay , Kotagal Prakash , Lachhwani Deepak , Wyllie Elaine , Lüders Hans O. , Bingaman William E.
Published: September 2005

Summary:  Purpose: To report our experience with hemispherectomy in the treatment of catastrophic epilepsy in children younger than 2 years.

Methods: In a single‐surgeon series, we performed a retrospective analysis of 18 patients with refractory epilepsy undergoing hemispherectomy (22 procedures). Three different surgical techniques were performed: anatomic hemispherectomy, functional hemispherectomy, and modified anatomic hemispherectomy. Pre‐ and postoperative evaluations included extensive video‐EEG monitoring, magnetic resonance imaging, and positron emission tomography scanning. Seizure outcome was correlated with possible variables associated with persistent postoperative seizures. The Generalized Estimation Equation (GEE) and the Barnard's exact test were used as statistical methods.

Results: The follow‐up was 12–74 months (mean, 34.8 months). Mean weight was 9.3 kg (6–12.3 kg). The population age was 3–22 months (mean, 11.7 months). Thirteen (66%) patients were seizure free, and four patients had >90% reduction of the seizure frequency and intensity. The overall complication rate was 16.7%. No deaths occurred. Twelve (54.5%) of 22 procedures resulted in incomplete disconnection, evidenced on postoperative images. Type of surgical procedure, diagnosis categories, persistence of insular cortex, and bilateral interictal epileptiform activity were not associated with persistent seizures after surgery. Incomplete disconnection was the only variable statistically associated with persistent seizures after surgery (p < 0.05).

Conclusions: Hemispherectomy for seizure control provides excellent and dramatic results with a satisfactory complication rate. Our results support the concept that early surgery should be indicated in highly selected patients with catastrophic epilepsy. Safety factors such as an expert team in the pediatric intensive care unit, neuroanesthesia, and a pediatric epilepsy surgeon familiar with the procedure are mandatory.
Consequences of Prolonged Caffeine Administration and Its Withdrawal on Pilocarpine‐ and Kainate‐induced Seizures in Rats
Authors: Hoexter Marcelo Q. , Rosa Pedro S. , Tufik Sergio , Mello Luiz E.
Published: September 2005

Summary:  Purpose: To investigate the consequences of caffeine consumption on epileptic seizures, we used the pilocarpine and the kainate models of epilepsy. We hypothesized that prolonged caffeine consumption or its withdrawal would alter adenosine levels and hence alter seizure susceptibility.

Methods: We administered a 0.1% caffeine solution in the drinking water of adult male Wistar rats over a 2‐week period. We challenged another group of animals with the same doses of pilocarpine or kainate 12 h after the withdrawal of the same caffeine‐administration protocol.

Results: This did not alter the threshold for the induction of seizures by a subconvulsant dose of pilocarpine (200 mg/kg, i.p.) or kainic acid (8 mg/kg, i.p.). Similarly, challenging another group of animals with the same doses of pilocarpine or kainate 12 h after the withdrawal of the same caffeine‐administration protocol did not lead to any significant changes in seizures.

Conclusions: With the pilocarpine model of epilepsy, we were not able to find any significant difference in seizure profile that could stem from either caffeine administration or its withdrawal. Despite the extensive laboratory evidence on the convulsant properties of xanthine derivatives in animal models of epilepsy, such strong evidence is lacking in clinical settings. Our current findings with the administration of caffeine at doses similar to those of daily life both support and confirm the clinical experience.
Clinical Features of Patients with Posterior Cortex Epilepsies and Predictors of Surgical Outcome
Authors: Dalmagro Charles L. , Bianchin Marino M. , Velasco Tonicarlo R. , Alexandre Veriano , Walz Roger , Terra‐Bustamante Vera C. , Inuzuka Luciana M. , Wichert‐Ana Lauro , Araújo David , Serafini Luciano N. , Carlotti Carlos G. , Assirati João A. , Machado Hélio R. , Santos Antonio C. , Sakamoto Américo C.
Published: September 2005

Summary:  Purpose: Posterior cortex epilepsies (PCEs) encompass a group of epilepsies originating from the occipital, parietal, or occipital border of the temporal lobe, or from any combination of these regions. When their seizures are refractory to pharmacologic treatment, these patients are usually referred for surgery. The aim of our study was to analyze clinical characteristics of all PCE patients referred for surgery from 1994 to 2003, and to search for predictors of surgical outcome.

Methods: We performed a retrospective analysis of clinical and laboratory data from 81 consecutive refractory PCE patients referred for surgery. Surgical and nonsurgical groups of patients were compared, and detailed analyses of all variables of the surgical cases were performed in the search for predictors of seizure outcome.

Results: Risk factors for PCEs included gliosis (34.56%), malformations of cortical development (33.33%), tumors (8.64%), brain trauma (3.70%), Sturge–Weber disease (4.93%), vascular malformations (3.70%), family history of epilepsy (3.70%), history of CNS infections (2.46%), and low IQ (2.46%). Of the 81 patients, 44 were submitted to surgery at the time of the completion of this study. Surgical treatment was highly effective in improving seizures (p < 0.001) when compared with previous pharmacologic treatment alone. Twenty‐eight (65.11%) patients became seizure free after surgery versus none in the nonsurgical group. Regarding outcome predictors, patients with shorter duration of epilepsy and those without neurologic abnormalities on clinical examination had higher chances of favorable evolution.

Conclusions: Surgical treatment is effective for the treatment of PCEs and superior to pharmacologic therapy alone. In our series, shorter duration of epilepsy and normal neurologic examination were the only independent variables that predicted better surgical outcome.
A Comparison of Case‐Control and Family‐Based Association Methods: The Example of Sickle‐Cell and Malaria
Authors: Ackerman H. , Usen S. , Jallow M. , Sisay‐Joof F. , Pinder M. , Kwiatkowski D. P.
Published: September 2005

There has been much debate about the relative merits of population‐ and family‐based strategies for testing genetic association, yet there is little empirical data that directly compare the two approaches. Here we compare case‐control and transmission/disequilibrium test (TDT) study designs using a well‐established genetic association, the protective effect of the sickle‐cell trait against severe malaria. We find that the two methods give similar estimates of the level of protection (case‐control odds ratio = 0.10, 95% confidence interval 0.03–0.23; family‐based estimate of the odds ratio = 0.11, 95% confidence interval 0.04–0.25) and similar statistical significance of the result (case‐control: χ2= 41.26, p= 10−10, TDT: χ2= 39.06, p= 10−10) when 315 TDT cases are compared to 583 controls. We propose a family plus population control study design, which allows both case‐control and TDT analysis of the cases. This combination is robust against the respective weaknesses of the case‐control and TDT study designs, namely population structure and segregation distortion. The combined study design is especially cost‐effective when cases are difficult to ascertain and, when the case‐control and TDT results agree, offers greater confidence in the result.
Fishing for Pleiotropic QTLs in a Polygenic Sea
Authors: Bauman L. E. , Almasy L. , Blangero J. , Duggirala R. , Sinsheimer J. S. , Lange K.
Published: September 2005

The application of factor analysis to human genetics has the potential to discover the coordinated control of multiple traits by common environment, common polygenes, or a single major gene. Classical factor analysis explains the covariation among the components of a random vector by approximating the vector by a linear transformation of a small number of uncorrelated factors. In the current paper we show how factor analysis dovetails with the classical variance decompositions of biometrical genetics. To explore the relationships between related quantitative variables, and avoid complicated positive definiteness constraints, we employ Cholesky and factor analytic decompositions. We derive an ECM algorithm and a competing quasi‐Newton algorithm for estimating parameters by maximum likelihood and propose tactics for selecting initial parameter values. We also show how parameter asymptotic standard errors under these parameterizations propagate to asymptotic standard errors of the underlying variance components. Our genetic analysis program Mendel, which now incorporates the program Fisher, has performed well on a variety of data sets. We illustrate our methods, algorithms, and models on two data sets: a bivariate quantitative genetic example using total finger ridge count data and a multivariate linkage example using insulin resistance data.