Assessment of psychosocial adjustment in patients with temporal lobe epilepsy using a standard measure

Despite the growing evidence of poor psychosocial adjustment, at present there is no formal method of assessment of social adjustment in patients with temporal lobe epilepsy (TLE). First, we assessed social adjustment in patients with TLE using a self-report questionnaire and compared the results with those from quality-of-life (QOL) scales. Second, we verified the influence of cognitive performance and clinical variables of epilepsy on social adjustment and QOL We evaluated 35 people with TLE and 38 healthy controls. Patients had worse social adjustment, and it was correlated with worse perception of cognitive function. Attention and verbal memory dysfunctions were negatively correlated with social adjustment. However, there was no significant correlation between cognitive performance and QOL Regarding clinical variables, persons with left TLE showed worse social adjustment and patients with frequent seizures showed worse QOL These findings indicate the relevance of evaluating social adjustment and emphasize the importance of cognitive rehabilitation to improved social adjustment. (c) 2010 Elsevier Inc. All rights reserved.

Effect of PaCO(2) variation on standard base excess value in critically ill patients

Purpose: The aim of this study was to investigate the impact of acute PaCO(2) temporal variation on the standard base excess (SBE) value in critically ill patients. Methods: A total of 265 patients were prospectively observed; 158 were allocated to the modeling group, and 107 were allocated to the validation group. Two models were developed in the modeling group (one including and one excluding PaCO(2) as a variable determinant of SBE), and both were tested in the validation group. Results: In the modeling group, the mathematical model including SIDai, SIG, L-lactate, albumin, phosphate, and PaCO(2) had a predictive superiority in comparison with the model without PaCO(2) (R(2) = 0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F change statistics (R(2) change = 0.059, P < .001) between the model with and without PaCO(2). A high correlation (R = 0.99, P < .001) and agreement (bias = -0.25 mEq/L, limits of agreement 95% = -0.72 to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the Van Slyke equation. Conclusions: Acute PaCO(2), temporal variation is related to SBE changes in critically ill patients. (C) 2009 Elsevier Inc. All rights reserved.

Predictive models for diagnosis of pleural effusions secondary to tuberculosis or cancer

Background and objective: Tuberculosis (TB) and cancer are two of the main causes of pleural effusions which frequently share similar clinical features and pleural fluid profiles. This study aimed to identify diagnostic models based on clinical and laboratory variables to differentiate tuberculous from malignant pleural effusions. Methods: A retrospective study of 403 patients (200 with TB; 203 with cancer) was undertaken. Univariate analysis was used to select the clinical variables relevant to the models composition. Variables beta coefficients were used to define a numerical score which presented a practical use. The performances of the most efficient models were tested in a sample of pleural exudates (64 new cases). Results: Two models are proposed for the diagnosis of effusions associated with each disease. For TB: (i) adenosine deaminase (ADA), globulins and the absence of malignant cells in the pleural fluid; and (ii) ADA, globulins and fluid appearance. For cancer: (i) patient age, fluid appearance, macrophage percentage and presence of atypical cells in the pleural fluid; and (ii) as for (i) excluding atypical cells. Application of the models to the 64 pleural effusions showed accuracy higher than 85% for all models. Conclusions: The proposed models were effective in suggesting pleural tuberculosis or cancer.

Relationship between Optical Coherence Tomography, Pattern Electroretinogram and Automated Perimetry in Eyes with Temporal Hemianopia from Chiasmal Compression

PURPOSE. To evaluate the relationship between pattern electroretinogram (PERG) amplitude, macular and retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT), and visual field (VF) loss on standard automated perimetry (SAP) in eyes with temporal hemianopia from chiasmal compression. METHODS. Forty-one eyes from 41 patients with permanent temporal VF defects from chiasmal compression and 41 healthy subjects underwent transient full-field and hemifield (temporal or nasal) stimulation PERG, SAP and time domain-OCT macular and RNFL thickness measurements. Comparisons were made using Student`s t-test. Deviation from normal VF sensitivity for the central 18 of VF was expressed in 1/Lambert units. Correlations between measurements were verified by linear regression analysis. RESULTS. PERG and OCT measurements were significantly lower in eyes with temporal hemianopia than in normal eyes. A significant correlation was found between VF sensitivity loss and fullfield or nasal, but not temporal, hemifield PERG amplitude. Likewise a significant correlation was found between VF sensitivity loss and most OCT parameters. No significant correlation was observed between OCT and PERG parameters, except for nasal hemifield amplitude. A significant correlation was observed between several macular and RNFL thickness parameters. CONCLUSIONS. In patients with chiasmal compression, PERG amplitude and OCT thickness measurements were significant related to VF loss, but not to each other. OCT and PERG quantify neuronal loss differently, but both technologies are useful in understanding structure-function relationship in patients with chiasmal compression. (ClinicalTrials.gov number, NCT00553761.) (Invest Ophthalmol Vis Sci. 2009; 50: 3535-3541) DOI:10.1167/iovs.08-3093

Association between degenerative aortic valve disease and long-term exposure to cardiovascular risk factors: results of the longitudinal population-based KORA/MONICA survey

Degenerative aortic valve disease (DAVD), a common finding in the elderly, is associated with an increased risk of death due to cardiovascular causes. Taking advantage of its longitudinal design, this study evaluates the prevalence of DAVD and its temporal associations with long-term exposure to cardiovascular risk factors in the general population. We studied 953 subjects (aged 25-74 years) from a random sample of German residents. Risk factors had been determined at a baseline investigation in 1994/95. At a follow-up investigation, 10 years later, standardized echocardiography determined aortic valve morphology and aortic valve area (AVA) as well as left ventricular geometry and function. At the follow-up study, the overall prevalence of DAVD was 28%. In logistic regression models adjusting for traditional cardiovascular risk factors at baseline age (OR 2.0 [1.7-2.3] per 10 years, P < 0.001), active smoking (OR 1.7 [1.1-2.4], P = 0.009) and elevated total cholesterol levels (OR 1.2 [1.1-1.3] per increase of 20 mg/dL, P < 0.001) were significantly related to DAVD at follow-up. Furthermore, age, baseline status of smoking, and total cholesterol level were significant predictors of a smaller AVA at follow-up study. In contrast, hypertension and obesity had no detectable relationship with long-term changes of aortic valve structure. In the general population we observed a high prevalence of DAVD that is associated with long-term exposure to elevated cholesterol levels and active smoking. These findings strengthen the notion that smoking cessation and cholesterol lowering are promising treatment targets for prevention of DAVD.

Executive dysfunction in children and adolescents with temporal lobe epilepsy: Is the Wisconsin Card Sorting Test enough?

The Wisconsin Card Sorting Test (WCST) is the gold standard in the evaluation of executive dysfunction (ED) in patients with temporal lobe epilepsy (TLE). We evaluated 35 children with TLE and 25 healthy controls with the WCST and with a more comprehensive battery. Among the children with TLE, 77.14% showed impairment on the WCST. On other tests (Wechsler Intelligence Scale for Children-Digit Forward, Matching Familiar Figures Test, Trail Making Test, Word Fluency, Finger Windows, and Number-Letter Memory), impairment was demonstrated in 94.29%. The authors concluded that the WCST is a good paradigm to measure executive impairment in children with TLE: however, it may be not enough. Evaluation performed only with the WCST not only underestimated the number of patients with ED, but also missed relevant information regarding the type of ED. (C) 2009 Elsevier Inc. All rights reserved.

Targeted Mutagenesis in Pathogenic Leptospira Species: Disruption of the LigB Gene Does Not Affect Virulence in Animal Models of Leptospirosis

The pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetically manipulating pathogenic Leptospira species. Thus, homologous recombination between introduced DNA and the corresponding chromosomal locus has never been demonstrated for this pathogen. Leptospiral immunoglobulin-like repeat (Lig) proteins were previously identified as putative Leptospira virulence factors. In this study, a ligB mutant was constructed by allelic exchange in L. interrogans; in this mutant a spectinomycin resistance (Spc(r)) gene replaced a portion of the ligB coding sequence. Gene disruption was confirmed by PCR, immunoblot analysis, and immunofluorescence studies. The ligB mutant did not show decrease virulence compared to the wild-type strain in the hamster model of leptospirosis. In addition, inoculation of rats with the ligB mutant induced persistent colonization of the kidneys. Finally, LigB was not required to mediate bacterial adherence to cultured cells. Taken together, our data provide the first evidence of site-directed homologous recombination in pathogenic Leptospira species. Furthermore, our data suggest that LigB does not play a major role in dissemination of the pathogen in the host and in the development of acute disease manifestations or persistent renal colonization.

Good surgical outcome in discordant ictal EEG-MRI unilateral mesial temporal sclerosis patients

Purpose:Video electroencephalography (vEEG) monitoring of patients with unilateral mesial temporal sclerosis (uMTS) may show concordant or discordant seizure onset in relation to magnetic resonance imaging (MRI) evidence of MTS. Contralateral seizure usually leads to an indication of invasive monitoring. Contralateral seizure onset on invasive monitoring may contraindicate surgery. We evaluated long-term outcome after anteromesial temporal lobectomy (AMTL) in a consecutive series of uMTS patients with concordant and discordant vEEG findings, uniformly submitted to AMTL on the MRI evidence of MTS side without invasive monitoring. Methods:We compared surgical outcome of all uMTS patients undergoing vEEG monitoring between January 1999 and April 2005 in our service. Discordant cases were defined by at least one seizure onset contralateral to the MRI evidence of MTS. Good surgical outcome was considered as Engel`s class I. We also evaluated ictal SPECT concordance to ictal EEG and surgical outcome. Results:Fifty-four patients had concordant (C) and 22 had discordant (D) scalp EEG and MRI. Surgical outcome was similar in both groups (C = 74% versus D = 86%). Duration of follow-up was comparable in both groups: C = 56.1 +/- 20.7 months versus D = 59.8 +/- 21.2 months (p = 0.83, nonsignificant). Discordant single-photon emission computed tomography (SPECT) results did not influence surgical outcome. Discussion:Surgical outcome was not influenced by contralateral vEEG seizure onset or contralateral increased flow on ictal SPECT. Although vEEG monitoring should still be performed in these patients, to rule out psychogenic seizures and extratemporal seizure onset, a potentially risky procedure such as invasive monitoring may not only not be indicated in this patient population, but may also lead to patients erroneously being denied surgery.

The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis

Purpose: As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor kappa B (NF kappa B), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanisms of several brain disorders such as stroke, bipolar disorder, schizophrenia, and disease. The aim of the present work was to localize and quantify AngII AT1 and AT2 receptors in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis (MTS) submitted to corticoamygdalohippocampectomy for seizure control. Method: Immunohistochemistry, Western blot, and real-time PCR techniques were employed to analyze the expression of these receptors. Results: The results showed an upregulation of AngII AT1 receptor as well as its messenger ribonucleic acid (mRNA) expression in the cortex and hippocampus of patients with MTS. In addition, an increased immunoexpression of AngII AT2 receptors was found only in the hippocampus of these patients with no changes in its mRNA levels. Discussion: These data show, for the first time, changes in components of renin-angiotensin system (RAS) that could be implicated in the physiopathology of MTS.

EFFECTS OF A POTENT PEROXYNITRITE DECOMPOSITION CATALYST IN MURINE MODELS OF ENDOTOXEMIA AND SEPSIS

Excessive free-radical production due to various bacterial components released during bacterial infection has been linked to cell death and tissue injury. Peroxynitrite is a highly reactive oxidant produced by the combination of nitric oxide (NO) and superoxide anion, which has been implicated in cell death and tissue injury in various forms of critical illness. Pharmacological decomposition of peroxynitrite may represent a potential therapeutic approach in diseases associated with the overproduction of NO and superoxide. In the present study, we tested the effect of a potent peroxynitrite decomposition catalyst in murine models of endotoxemia and sepsis. Mice were injected i.p. with LPS 40 mg/kg with or without FP15 [Fe(III) tetrakis-2-(N-triethylene glycol monomethyl ether) pyridyl porphyrin] (0.1, 0.3, 1, 3, or 10 mg/kg per hour). Mice were killed 12 h later, followed by the harvesting of samples from the lung, liver, and gut for malondialdehyde and myeloperoxidase measurements. In other subsets of animals, blood samples were obtained by cardiac puncture at 1.5, 4, and 8 h after LPS administration for cytokine (TNF-alpha, IL-1 beta, and IL-10), nitrite/nitrate, alanine aminotransferase, and blood urea nitrogen measurements. Endotoxemic animals showed an increase in survival from 25% to 80% at the FP15 doses of 0.3 and 1 mg/kg per hour. The same dose of FP15 had no effect on plasma levels of nitrite/nitrate. There was a reduction in liver and lung malondialdehyde in the endotoxemic animals pretreated with FP15, as well as in hepatic myeloperoxidase and biochemical markers of liver and kidney damage (alanine aminotransferase and blood urea nitrogen). In a bacterial model of sepsis induced by cecal ligation and puncture, FP15 treatment (0.3 mg/kg per day) significantly protected against mortality. The current data support the view that peroxynitrite is a critical factor mediating liver, gut, and lung injury in endotoxemia and septic shock: its pharmacological neutralization may be of therapeutic benefit.

Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans

The adenovirus type 5 (Ad5)-based vaccine developed by Merck failed to either prevent HIV-1 infection or suppress viral load in subsequently infected subjects in the STEP human Phase 2b efficacy trial. Analogous vaccines had previously also failed in the simian immunodeficiency virus (SIV) challenge-rhesus macaque model. In contrast, vaccine protection studies that used challenge with a chimeric simian-human immunodeficiency virus (SHIV89.6P) in macaques did not predict the human trial results. Ad5 vector -based vaccines did not protect macaques from infection after SHIV89.6P challenge but did cause a substantial reduction in viral load and a preservation of CD4(+) T cell counts after infection, findings that were not reproduced in the human trials. Although the SIV challenge model is incompletely validated, we propose that its expanded use can help facilitate the prioritization of candidate HIV-1 vaccines, ensuring that resources are focused on the most promising candidates. Vaccine designers must now develop T cell vaccine strategies that reduce viral load after heterologous challenge.

Higgs pair production at the LHC in models with universal extra dimensions

In this Letter we study the process of gluon fusion into a pair of Higgs bosons in a model with one universal extra dimension. We find that the contributions from the extra top quark Kaluza-Klem excitations lead to a Higgs pair production cross section at the LHC that can be significantly altered compared to the Standard Model value for small values of the compactification scale. (C) 2007 Elsevier B.V. All rights reserved.

Crotamine toxicity and efficacy in mouse models of melanoma

Objectives: Selective anticancer cell activity for both cell-penetrating and cationic antimicrobial peptides has previously been reported. As crotamine possesses activities similar to both of these, this study investigates crotamine`s anticancer toxicity in vitro and in vivo. Research design and methods: In vitro cancer cell viability was evaluated after treatment with 1 and 5 mu g/ml of crotamine. In vivo crotamine cytotoxic effects in C57Bl/6J mice bearing B16-F10 primary cutaneous melanoma were tested, with two groups each containing 35 mice. The crotamine-treated group received 1 mu g/day of crotamine per animal, subcutaneously which was well tolerated; the untreated group received a placebo. Results: Crotamine at 5 mu g/ml was lethal to B16-F10, Mia PaCa-2 and SK-Mel-28 cells and inoffensive to normal cells. In vivo crotamine treatment over 21 days significantly delayed tumor implantation, inhibited tumor growth and prolonged the lifespan of the mice. Mice in the crotamine-treated group survived at significantly higher rates (n = 30/35) than those in the untreated group (n = 7/35) (significance calculated with the Kaplan-Meier estimator). The average tumor weight in the untreated group was 4.60 g but was only about 0.27 g in the crotamine-treated mice, if detectable. Conclusions: These data warrant further exploration of crotamine as a tumor inhibition compound.

Modulation of B-1 and B-2 kinin receptors expression levels in the hippocampus of rats after audiogenic kindling and with limbic recruitment, a model of temporal lobe epilepsy

Epileptic seizures are hypersynchronous, paroxystic and abnormal neuronal discharges. Epilepsies are characterized by diverse mechanisms involving alteration of excitatory and inhibitory neurotransmission that result in hyperexcitability of the central nervous system (CNS). Enhanced neuronal excitability can also be achieved by inflammatory processes, including the participation of cytokines, prostaglandins or kinins, molecules known to be involved in either triggering or in the establishment of inflammation. Multiple inductions of audiogenic seizures in the Wistar audiogenic rat (WAR) strain are a model of temporal lobe epilepsy (TLE), due to the recruitment of limbic areas such as hippocampus and amygdata. In this study we investigated the modulation of the B-1 and B-2 kinin receptors expression levels in neonatal WARs as well as in adult WARs subjected to the TLE model. The expression levels of pro-inflammatory (IL-1 beta) and anti-inflammatory (IL-10) cytokines were also evaluated, as well as cyclooxygenase (COX-2). Our results showed that the B-1 and B-2 kinin receptors mRNAs were up-regulated about 7- and 4-fold, respectively, in the hippocampus of kindled WARs. On the other hand, the expressions of the IL-1 beta, IL-10 and COX-2 were not related to the observed increase of expression of kinin receptors. Based on those results we believe that the B, and B2 kinin receptors have a pivotal role in this model of TLE, although their participation is not related to an inflammatory process. We believe that kinin receptors in the CNS may act in seizure mechanisms by participating in a specific kininergic neurochemical pathway. (c) 2007 Elsevier B.V. All rights reserved.

Utility of Ictal Single Photon Emission Computed Tomography in Mesial Temporal Lobe Epilepsy With Hippocampal Atrophy: A Randomized Trial

BACKGROUND: The development of newer diagnostic technologies has reduced the need for invasive electroencephalographic (EEG) studies in identifying the epileptogenic zone, especially in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). OBJECTIVE: To evaluate ictal single photon emission computed tomography (SPECT) in the evaluation and treatment of patients with MTLE-HS. METHODS: MTLE patients were randomly assigned to those with (SPECT, n = 124) and without ictal SPECT (non-SPECT, n = 116) in an intent-to-treat protocol. Primary end points were the proportion of patients with invasive EEG studies, and those offered surgery. Secondary end points were the length of hospital stay and the proportion of patients with secondarily generalized seizures (SGS) during video-EEG, postsurgical seizure outcome, and hospital cost. RESULTS: The proportion of patients offered surgery was similar in the SPECT (85%) and non-SPECT groups (81%), as well as the proportion that had invasive EEG studies (27% vs 23%). The mean duration of hospital stay was 1 day longer for the SPECT group (P < 0.001). SGS occurred in 51% of the SPECT and 26% of the non-SPECT group (P < 0.001). The cost of the presurgical evaluation was 35% higher for the SPECT compared with the non-SPECT group (P < 0.001). The proportion of patients seizure-free after surgery was similar in the SPECT (59%) compared with non-SPECT group (54%). CONCLUSION: Ictal-SPECT did not add localizing value beyond what was provided by EEG-video telemetry and structural MRI that altered the surgical decision and outcome for MTLE-HS patients. Ictal-SPECT increased hospital stay was associated with increased costs and a higher chance of SGS during video-EEG monitoring. These findings support the notion that a protocol including ictal SPECT is equivalent to one without SPECT in the presurgical evaluation of adult patients with MTLE-HS.