Toxicity of concurrent radiochemotherapy for locally advanced non--small-cell lung cancer: a systematic review of the literature.

Concurrent radiochemotherapy (RCT) is the treatment of choice for patients with locally advanced non-small-cell lung cancer (NSCLC). Two meta-analyses were inconclusive in an attempt to define the optimal concurrent RCT scheme. Besides efficacy, treatment toxicity will influence the appointed treatment of choice. A systematic review of the literature was performed to record the early and late toxicities, as well as overall survival, of concurrent RCT regimens in patients with NSCLC. The databases of PubMed, Ovid, Medline, and the Cochrane Library were searched for articles on concurrent RCT published between January 1992 and December 2009. Publications of phase II and phase III trials with ≥ 50 patients per treatment arm were selected. Patient characteristics, chemotherapy regimen (mono- or polychemotherapy, high or low dose) and radiotherapy scheme, acute and late toxicity, and overall survival data were compared. Seventeen articles were selected: 12 studies with cisplatin-containing regimens and 5 studies using carboplatin. A total of 13 series with mono- or polychemotherapy schedules--as single dose or double or triple high-dose or daily cisplatin-containing (≤ 30 mg/m(2)/wk) chemotherapy were found. Acute esophagitis ≥ grade 3 was observed in up to 18% of the patients. High-dose cisplatin regimens resulted in more frequent and severe hematologic toxicity, nausea, and vomiting than did other schemes. The toxicity profile was more favorable in low-dose chemotherapy schedules. From phase II and III trials published between 1992 and 2010, it can be concluded that concurrent RCT with monochemotherapy consisting of daily cisplatin results in favorable acute and late toxicity compared with concurrent RCT with single high-dose chemotherapy, doublets, or triplets.

Behavioral flexibility impairment with negative feedback in refractory temporal lobe epileptic patients with unilateral amygdala and hippocampal resection.

INTRODUCTION: Patients with amygdala dysfunction generally have behavioral impairment. Temporal lobe surgery might be a model of study of unilateral amygdala resection. The objective of this study was to evaluate behavioral flexibility in epileptic patients who undergo amygdala resection for epilepsy surgery and evaluate its relationship with their neuropsychiatric symptoms. MATERIAL AND METHODS: Ten epileptic patients who underwent amygdala and hippocampal resection (6 left and 4 right) matched by age and educational level with 10 healthy controls were tested with an extensive neuropsychological and neuropsychiatric battery. Psychiatric symptomatology was measured with the positive and negative syndrome scale (PANSS) and the Beck depression inventory. To assess behavioral flexibility the emotion-related visual reversal-learning task (O'Doherty et al., 2001) and the gambling task (Bechara et al., 1994) were used. RESULTS: Patient's mean scores were: Beck: 8 +/- 1.5; PANSS positive: 10 +/- 1.3, and negative: 14.4 +/- 2.2; intellectual quotient (IQ): 101.4 +/- 6.3; category number in Wisconsin card sorting test: 4.6 +/- 2.4. The emotion-related visual reversal-learning task showed significance differences in the number of reversion: healthy controls: 9.3; epileptic patients: 4.23 (p < 0.001); in the number of trials to the first reversion: healthy controls: 5; epileptic patients: 23.42 (p < 0.05). There was no correlation between reversion and depression, PANSS and IQ. CONCLUSIONS: Patients with epilepsy who undergo unilateral hippocampal and amygdala resection appear to have alterations in the reversion capacity with an emotional component that would explain the lack of behavior flexibility that they sometimes have and that are not related with either the isolated presence of executive alterations or low intellectual quotient.

Flexibilidad conductual ante un feedback negativo en pacientes epilépticos temporales refractarios con resección amigdalohipocámpica unilateral / Behavioral flexibility impairment with negative feedback in refractory temporal lobe epileptic patients with unilateral amygdala and hippocampal resection

Introducción. Los pacientes con disfunciones amigdalinas suelen presentar alteraciones en su conducta. La cirugía de epilepsia temporal proporciona un modelo de estudio de la resección amigdalina unilateral. El objetivo de este trabajo fue estudiar la flexibilidad conductual ante un feedback afectivo negativo en pacientes con resección de amígdala por cirugía de epilepsia y evaluar su relación con los síntomas neuropsiquiátricos. Material y métodos. Diez pacientes con epilepsia del lóbulo temporal (ELT) con resección de amígdala e hipocampo, 6 derechas y 4 izquierdas, apareados por edad y nivel de educación con 10 sujetos controles normales, fueron evaluados con una extensa batería neuropsicológica y neuropsiquiátrica que incluyó la Escala de síndromes positivos y negativos (PANSS) y la Escala de depresión de Beck. Para estudiar la adaptabilidad conductual se utilizaron el Test de Aprendizaje y reversión afectiva (O'Doherty et al., 2001) y el Test del Casino (Bechara et al., 1994). Resultados. Los pacientes tenían los siguientes puntajes (en media ± DE): escala de Beck de 8 ± 1,5, PANSS positiva de 10 ± 1,3 y negativa de 14,4 ± 2,2, un cociente intelectual (CI) de 101,4 ± 6,3, las categorías completadas en el Test de las cartas de Wisconsin fueron de 4,6 ± 2,4. En el test de aprendizaje y reversión afectiva mostraron diferencias significativas en el número de reversiones: controles, 9,3; ELT, 4,23 (p < 0,001), y en los ensayos para lograr la primera reversión: controles, 5; ELT, 23,42 (p < 0,05). No hubo correlación significativa entre las variables de reversión, depresión, la puntuación de la PANSS o el CI. Conclusiones. Los pacientes epilépticos con resección amigdalohipocámpica unilateral tendrían alteraciones en la capacidad de reversión con componente afectivo que explicarían la falta de flexibilidad conductual que a veces presentan los mismos y que no se relacionan ni con la presencia aislada de alteraciones ejecutivas ni con un bajo cociente intelectual

Introduction. Patients with amygdala dysfunction generally have behavioral impairment. Temporal lobe surgery might be a model of study of unilateral amygdala resection. The objective of this study was to evaluate behavioral flexibility in epileptic patients who undergo amygdala resection for epilepsy surgery and evaluate its relationship with their neuropsychiatric symptoms. Material and methods. Ten epileptic patients who underwent amygdala and hippocampal resection (6 left and 4 right) matched by age and educational level with 10 healthy controls were tested with an extensive neuropsychological and neuropsychiatric battery. Psychiatric symptomatology was measured with the positive and negative syndrome scale (PANSS) and the Beck depression inventory. To assess behavioral flexibility the emotion-related visual reversal-learning task (O'Doherty et al., 2001) and the gambling task (Bechara et al., 1994) were used. Results. Patient's mean scores were: Beck: 8 ± 1.5; PANSS positive: 10 ± 1.3, and negative: 14.4 ± 2.2; intellectual quotient (IQ): 101.4 ± 6.3; category number in Wisconsin card sorting test: 4.6 ± 2.4. The emotion-related visual reversal-learning task showed significance differences in the number of reversion: healthy controls: 9.3; epileptic patients: 4.23 (p < 0.001); in the number of trials to the first reversion: healthy controls: 5; epileptic patients: 23.42 (p < 0.05). There was no correlation between reversion and depression, PANSS and IQ. Conclusions. Patients with epilepsy who undergo unilateral hippocampal and amygdala resection appear to have alterations in the reversion capacity with an emotional component that would explain the lack of behavior flexibility that they sometimes have and that are not related with either the isolated presence of executive alterations or low intellectual quotient

Enhanced provider communication and patient education regarding return to work in cancer survivors following curative treatment: a pilot study.

BACKGROUND: For employed cancer survivors, returning to work and maintaining employment is an important aspect of their quality of life. We developed an intervention aimed at enhancing this by means of (a) providing the patient with an educational leaflet on return to work and (b) enhancing communication between attending and occupational physicians. The purpose of this study is to test the feasibility of this intervention and to examine the relation of patient adherence to the advice of the leaflet and return to work. METHODS: A patient series of 35 employed cancer survivors was used to evaluate the intervention. Survivors completed a baseline questionnaire prior to their treatment. Survivors and occupational physicians were interviewed by telephone eight weeks following all curative treatment. Our measure of feasibility included satisfaction of survivors with the intervention, adherence to the advice, time to return to work, satisfaction of occupational physicians with the intervention, and perceived influence on their rehabilitation efforts. RESULTS: Interviews of 26 survivors and 24 occupational physicians, revealed that those groups perceived the leaflet as useful (i.e., 7 on a 0-10 scale. Also seven out of ten suggestions in the leaflet was adhered to and half of the occupational physicians perceived the guidance they provided was helpful. However there was no effect of level of adherence on actual return to work. CONCLUSION: This pilot study demonstrated the feasibility of the approach used. However level of adherence to educational leaflet was not associated with an improvement in return to work in cancer survivors.

A nebular origin for chondritic fine-grained phyllosilicates.

Hydrated minerals occur in accretionary rims around chondrules in CM chondrites. Previous models suggested that these phyllosilicates did not form by gas-solid reactions in the canonical solar nebula. We propose that chondrule-forming shock waves in icy regions of the nebula produced conditions that allowed rapid mineral hydration. The time scales for phyllosilicate formation are similar to the time it takes for a shocked system to cool from the temperature of phyllosilicate stability to that of water ice condensation. This scenario allows for simultaneous formation of chondrules and their fine-grained accretionary rims.

Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2): structure, gene mapping, polymorphisms, and candidate evaluation for human orofacial clefts.

BACKGROUND: Nonsyndromic orofacial clefts have an estimated incidence of 1/1000 live births. Population genetic and embryologic studies suggest that cleft palate only (CPO) may be a distinct clinical entity from cleft lip with or without cleft palate (CL/P). Both CPO and CL/P are thought to be multifactorial in etiology, with evidence indicating that genetic, environmental, and developmental determinants may all play a role. The ARNT2 gene localizes to a conserved linkage group on mouse chromosome 7 that is syntenic with human chromosome 15q23-25. This chromosomal region was previously identified as a teratogen-induced clefting susceptibility locus in a genome-wide scan of AXB and BXA recombinant inbred mice. Arnt2 is expressed in the first branchial arch in mice. The teratogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) acts through the aryl hydrocarbon receptor (Ahr) pathway to produce dose-dependent CPO and thymic wasting in mice exposed in utero. Arnt2 and Ahr proteins dimerize in vitro. TCDD exposure is also associated with orofacial clefting in children of parents involved in agricultural work. METHODS: To determine whether ARNT2 influences human craniofacial development, we identified the human ARNT2 gene and conducted genomic structural analysis. Mutational screening was performed in infants with nonsyndromic CPO or CL/P who were identified by the Iowa Birth Defects Registry. RESULTS: A common amino acid polymorphism was detected but, no obvious disease-causing mutations were detected by SSCP analysis. The microsatellite marker, GATA89D04 (D15S823) was identified within intron 11 of the human ARNT2 gene, and linkage disequilibrium of nonsyndromic CPO and CL/P parent-infant trios was conducted. CONCLUSIONS: No association was demonstrated with CPO (n = 45) and CL/P (n = 37). Teratology 66:85-90, 2002.