The role of hybridization and introgression in maintaining species integrity and cohesion in naturally isolated inselberg bromeliad populations.

Hybridization is a widespread phenomenon present in numerous lineages across the tree of life. Its evolutionary consequences range from effects on the origin and maintenance, to the loss of biodiversity. We studied genetic diversity and intra- and interspecific gene flow between two sympatric populations of closely-related species, Pitcairnia flammea and P. corcovadensis (Bromeliaceae), which are adapted to naturally fragmented Neotropical inselbergs, based on nuclear and plastidial DNA. Our main results indicate a strong reproductive isolation barrier, although low levels of interspecific gene flow were observed in both sympatric populations. The low rates of intraspecific gene flow observed for both P. corcovadensis and P. flammea populations corroborate the increasing body of evidence that inselberg bromeliad species are maintained as discrete evolutionary units despite the presence of low genetic connectivity. Nuclear patterns of genetic diversity and gene flow revealed that hybridization and introgression might not cause species extinction via genetic assimilation of the rare P. corcovadensis. In the face of reduced intraspecific gene exchange, hybridization and introgression may be important aspects of the Pitcairnia diversification process, with a positive evolutionary impact at the bromeliad community level, and thus contribute to increasing and maintaining genetic diversity in local isolated inselberg populations.

Atypical perceptual and neural processing of emotional prosodic changes in children with autism spectrum disorders.

OBJECTIVE: The present study explored the processing of emotional speech prosody in school-aged children with autism spectrum disorders (ASD) but without marked language impairments (children with ASD [no LI]). METHODS: The mismatch negativity (MMN)/the late discriminative negativity (LDN), reflecting pre-attentive auditory discrimination processes, and the P3a, indexing involuntary orienting to attention-catching changes, were recorded to natural word stimuli uttered with different emotional connotations (neutral, sad, scornful and commanding). Perceptual prosody discrimination was addressed with a behavioral sound-discrimination test. RESULTS: Overall, children with ASD (no LI) were slower in behaviorally discriminating prosodic features of speech stimuli than typically developed control children. Further, smaller standard-stimulus event related potentials (ERPs) and MMN/LDNs were found in children with ASD (no LI) than in controls. In addition, the amplitude of the P3a was diminished and differentially distributed on the scalp in children with ASD (no LI) than in control children. CONCLUSIONS: Processing of words and changes in emotional speech prosody is impaired at various levels of information processing in school-aged children with ASD (no LI). SIGNIFICANCE: The results suggest that low-level speech sound discrimination and orienting deficits might contribute to emotional speech prosody processing impairments observed in ASD.

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. PATIENTS AND METHODS: This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. RESULTS: Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. CONCLUSIONS: In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis.

Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease.

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p<0.05). The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67). CONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting. KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

A 4-arm randomized controlled pilot trial of innovative solutions for jugular central venous access device securement in 221 cardiac surgical patients.

PURPOSE: To improve jugular central venous access device (CVAD) securement, prevent CVAD failure (composite: dislodgement, occlusion, breakage, local or bloodstream infection), and assess subsequent trial feasibility. MATERIALS AND METHODS: Study design was a 4-arm, parallel, randomized, controlled, nonblinded, pilot trial. Patients received CVAD securement with (i) suture+bordered polyurethane (suture + BPU; control), (ii) suture+absorbent dressing (suture + AD), (iii) sutureless securement device+simple polyurethane (SSD+SPU), or (iv) tissue adhesive+simple polyurethane (TA+SPU). Midtrial, due to safety, the TA+SPU intervention was replaced with a suture + TA+SPU group. RESULTS: A total of 221 patients were randomized with 2 postrandomization exclusions. Central venous access device failure was as follows: suture + BPU controls, 2 (4%) of 55 (0.52/1000 hours); suture + AD, 1 (2%) of 56 (0.26/1000 hours, P=.560); SSD+SPU, 4 (7%) of 55 (1.04/1000 hours, P=.417); TA+SPU, 4 (17%) of 23 (2.53/1000 hours, P=.049); and suture + TA+SPU, 0 (0%) of 30 (P=.263; intention-to-treat, log-rank tests). Central venous access device failure was predicted (P<.05) by baseline poor/fair skin integrity (hazard ratio, 9.8; 95% confidence interval, 1.2-79.9) or impaired mental state at CVAD removal (hazard ratio, 14.2; 95% confidence interval, 3.0-68.4). CONCLUSIONS: Jugular CVAD securement is challenging in postcardiac surgical patients who are coagulopathic and mobilized early. TA+SPU was ineffective for CVAD securement and is not recommended. Suture + TA+SPU appeared promising, with zero CVAD failure observed. Future trials should resolve uncertainty about the comparative effect of suture + TA+SPU, suture + AD, and SSD+SPU vs suture + BPU.

The brains of high functioning autistic individuals do not synchronize with those of others.

Multifaceted and idiosyncratic aberrancies in social cognition characterize autism spectrum disorders (ASDs). To advance understanding of underlying neural mechanisms, we measured brain hemodynamic activity with functional magnetic resonance imaging (fMRI) in individuals with ASD and matched-pair neurotypical (NT) controls while they were viewing a feature film portraying social interactions. Pearson's correlation coefficient was used as a measure of voxelwise similarity of brain activity (InterSubject Correlations-ISCs). Individuals with ASD showed lower ISC than NT controls in brain regions implicated in processing social information including the insula, posterior and anterior cingulate cortex, caudate nucleus, precuneus, lateral occipital cortex, and supramarginal gyrus. Curiously, also within NT group, autism-quotient scores predicted ISC in overlapping areas, including, e.g., supramarginal gyrus and precuneus. In ASD participants, functional connectivity was decreased between the frontal pole and the superior frontal gyrus, angular gyrus, superior parietal lobule, precentral gyrus, precuneus, and anterior/posterior cingulate gyrus. Taken together these results suggest that ISC and functional connectivity measure distinct features of atypical brain function in high-functioning autistic individuals during free viewing of acted social interactions. Our ISC results suggest that the minds of ASD individuals do not 'tick together' with others while perceiving identical dynamic social interactions.

[Errors and hazards in oncology: radiation oncology]. / Fehler und Gefahren: Medikamentöse und strahlentherapeutische Behandlung von -Kopf-Hals-Malignomen.

Adverse effects and hazards which have their origin from radiation using conventional techniques like 3-D conformal radiotherapy and total radiation doses are well known. However little is known about the sprectum of especially late toxicity after radiation using new technologies like intensity modulated radiotherapy (IMRT) combined with novel target volume and dose concepts. Since IMRT allows for selective protection of the large salivary glands this technique improves the intermediate term quality of life and is the standard of care despite many details need further prospective evaluation. Combining cytotoxic drugs and radiotherapy yield improved survival in well-defined high risk patients. However morbidity and mortality of these protocols are high and deserve special expertise and supportive therapy. EGF-receptor antibodies have gained well defined indications, albeit specific toxicities in combination with irradiation deserve prospective studies and special attention.

[Traffic medicine in rehabilitation]. / Verkehrsmedizin in der Rehabilitation.

Participation in road traffic in Germany is governed by various laws and acts. Physicians are obliged to decide whether, in the presence of medical conditions and handicaps, a patient is fit to drive a car safely. Following myocardial infarction this decision is generally made by specialized cardiologists (specialization in social medicine) in rehabilitation centers. If a patient does not undergo rehabilitation after an acute event, this decision must be made by the invasive cardiologist, who is often not skilled in this kind of assessment. The second problem faced in Germany is the discrepancy between outdated legal regulations, modern cardiology and the current standard of medical knowledge, especially in terms of treatment for acute coronary syndrome. According to current legal regulations, no patient at all is allowed to drive a car in Germany after any form of myocardial infarction, regardless of ejection fraction, for at least 3 months. In contrast, a working group for the German Society of Cardiology published a position paper in 2010 in which patients could be allowed to drive a car 2 weeks after an AMI with an EF >30. The third problem in this context in Germany is that, due to a decision by the Federal High Court of Justice, physicians are not only responsible to inform the patient, if he is not allowed to drive a car, but also have to assure that he does not leave the hospital or practice by car, if he is not allowed to. If the patient however opposes, drives home and has an accident, the physician is liable for the damages. The fourth and final problem lies in the fact that most cardiologists in Germany are neither skilled in legal traffic assessment, nor are they familiar with this field and its problems.

Sympatric bromeliad species (Pitcairnia spp.) facilitate tests of mechanisms involved in species cohesion and reproductive isolation in Neotropical inselbergs.

The roles of intra- and interspecific gene flow in speciation and species evolution are topics of great current interest in molecular ecology and evolutionary biology. Recent modelling studies call for new empirical data to test hypotheses arising from the recent shift from a 'whole-genome reproductive isolation' view to a 'genic' view of species and speciation. Particularly scarce (and thus of particular interest) are molecular genetic data on recently radiated, naturally hybridizing species in strongly structured and species-rich environments. Here, we studied four sympatric plant species (Pitcairnia spp.; Bromeliaceae) adapted to Neotropical inselbergs (isolated outcrops resembling habitat 'islands' in tropical rainforests) using nuclear and plastid DNA. Patterns of plastid DNA haplotype sharing and nuclear genomic admixture suggest the presence of both, incomplete lineage sorting and interspecific gene flow over extended periods of time. Integrity and cohesion of inselberg species of Pitcairnia are maintained despite introgression and in the face of extremely low within-species migration rates (N(e)m < 1 migrant per generation). Cross-evaluation of our genetic data against published pollination experiments indicate that species integrity is maintained by the simultaneous action of multiple prezygotic barriers, including flowering phenology, pollinator isolation and divergent mating systems. Postzygotic Bateson-Dobzhansky-Muller incompatibilities appear to contribute to isolation, as suggested by asymmetric introgression rates of single loci. Our results suggest that incomplete lineage sorting, hybridization and introgression form integral aspects of adaptive radiation in Neotropical inselberg 'archipelagos'. Inselbergs with multiple closely related co-occurring species should be of special interest to students of speciation in mountain systems, and to ongoing conservation programmes in the Atlantic Rainforest biodiversity hotspot.

Efecto de dosis bajas de ketamina en la analgesia postoperatoria y consumo de morfina tras cirugía de revascularización miocárdica / Efficacy of low doses of ketamine in postoperative analgesia and the use of morphine after myocardial revascularisation surgery

Objetivos. Valorar la eficacia de la ketamina administrada intraoperatoriamente a dosis bajas en infusión continua (8mg/kg/min) en la analgesia postoperatoria y en reducir el consumo de morfina en las primeras 24h del postoperatorio de cirugía de derivación coronaria tras anestesia basada en remifentanilo. Material y método. Estudio prospectivo, aleatorio y doble ciego en 60 pacientes, ASA III–IV, programados para ser sometidos a cirugía de revascularización miocárdica sin circulación extracorporea. Técnica anestésica estándar con propofol y remifentanilo entre 0,5–1mg/kg/min, tras la inducción anestésica, el grupo K (n=30) recibió una infusión de ketamina constante de 8mg/kg/min y el grupo P (n=30) suero salino 0,9% al mismo ritmo de infusión por vía intravenosa. Antes de finalizar la cirugía se administró 0,15mg/kg de morfina vía intravenosa. La analgesia postoperatoria se realizó con morfina 3mg cada 5min cuando la escala verbal simple (1). Valoramos el consumo de remifentanilo propofol intraoperatorio, tiempo hasta administrarse el primer analgésico, consumo de morfina en las primeras 24h, intensidad del dolor mediante escala verbal simple y escala visual analógica, parámetros hemodinámicos, respiratorios, nivel de sedación y efectos adversos. Resultados. No hemos encontrado diferencias estadísticamente significativas en las características demográficas, así como en el consumo e infusiones medias de remifentanilo y propofol de ambos grupos. Los pacientes del grupo K retrasaron significativamente el momento de solicitar la primera dosis de analgésico con respecto al grupo P (p<0,03), el consumo de morfina en la reanimación y el consumo total en las primeras 24h no mostró diferencias significativas entre ambos grupos de estudio. Resultados. Los parámetros hemodinámicos, respiratorios y nivel de sedación permanecieron estables durante todo el periodo de estudio sin diferencias estadísticamente significativas entre ambos grupos. El control del dolor postoperatorio fue adecuado en ambos grupos (escala visual analógica <30, escala verbal simple <2) sin diferencias significativas durante las 24h de estudio. En la incidencia de efectos adversos no hubo diferencias significativas entre ambos grupos, la incidencia de nauseas y vómitos postoperatorios fue del 20% en el grupo K y del 30% en el grupo P. Ningún paciente presentó alucinaciones o disforia. Conclusiones. Dosis bajas de ketamina en infusión continua durante el periodo intraoperatorio de cirugía coronaria prolongan el tiempo de demanda de la primera dosis de morfina, sin reducir el consumo de remifentanilo intraoperatorio, ni el consumo total de morfina durante en las primeras 24h de postoperatorio (AU)

Objectives. To assess the efficacy of ketamine in low doses by continuous infusion (8mg/kg/min) given during surgery and the reduction in morphine use in the first 24h after coronary bypass surgery with remifentanil based anaesthesia. Material and method. Randomised, prospective, double blind study on 60 patients, ASA III–IV, scheduled to have off-pump myocardial revascularisation surgery. A standard anaesthetic technique with propofol and remifentanil between 0.5−1mg/kg/min, after induction of anaesthesia, the ketamine (K) group (n=30) received a continuous infusion of 8mg/kg/min and the propofol and remifentanil (P) group (n=30) received 0.9% physiological saline intravenously at the same infusion rate. Before the end of the surgery 0.15mg/kg of morphine was given intravenously. Post-operative analgesia consisted of 3mg of morphine every 5min when the simple verbal scale was <1 (SVS<1). The intra-operative use of remifentanil–propofol was determined, as well as, the time to giving the first analgesic, pain intensity using the SVS and visual analogue scale (VAS), haemodynamic and respiratory parameters, level of sedation and adverse effects. Results. No statistically significant differences were found between the demographic parameters, or in the mean use and infusions of remifentanil and propofol by both groups. The patients from the K group significantly delayed the time of requesting the first analgesic dose compared to the P group (P<0.03). There were no significant differences between both study groups in the use of morphine in recovery and the total use in the first 24h. Results. The haemodynamic and respiratory parameters, and the sedation level remained stable during the whole period of the study, with no statistically significant differences between both groups. Post-operative pain control was adequate in both groups VAS<30, SVS<2), with no significant differences during the 24h of the study. There no significant differences between groups, in the incidence of adverse effects. The incidence of nausea and post-operative vomiting was 20% in group K and 30% in group P. None of the patients had hallucinations or dysphoria. Conclusions. Low doses of ketamine in continuous infusion during the intra-operative period of coronary surgery prolongs the time of demanding the first morphine dose, without reducing the use of intra-operative remifentanil, or the total use of morphine in the first 24h after surgery (AU)

Phase I trial of dose-escalated cisplatin with concomitant cetuximab and hyperfractionated-accelerated radiotherapy in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Cetuximab is active in the treatment of squamous cell carcinoma of the head and neck (SCCHN), enhancing both radiotherapy and chemotherapy effects. This phase I study was designed to investigate the safety and tolerability of combining weekly cisplatin treatment with cetuximab and hyperfractionated-accelerated radiotherapy (HART) for locally advanced SCCHN. PATIENTS AND METHODS: Patients with unresectable stage III or IVA/B SCCHN were treated with cetuximab, 400 mg/m² initial dose on day -7 of HART, followed by 250 mg/m² weekly during the administration of HART, which started with 2.0 Gy/day (5 days/week) for 3 weeks followed by 1.4 Gy/twice-daily (Monday to Friday) for another 3 weeks, resulting in a total dose of 70.6 Gy. Cisplatin was administered weekly starting on the first day of radiotherapy until week 6. Cisplatin was dose escalated of four dose levels from 20 to 40 mg/m² using a classical 3 + 3 dose escalation algorithm. RESULTS: Eighteen patients were enrolled. Sixteen patients were eligible for toxicity, and 15 for response. No maximum tolerated dose was reached for cisplatin. One of six patients of dose level 4 had grade 4 neutropenia. This patient died 1 week after the end of the study treatment. The most common types of grade 3+ adverse events were mucositis (9 of 16 patients), in-field dermatitis (6 of 16 patients) and neutropenia (4 of 16 patients). Cetuximab-related hypersensitivity was observed in 1 out of 18 patients. Six weeks after the end of the study treatment, 5 complete responses, 8 partial responses and 1 progressive disease (at distant sites) were documented in a total of 15 patients (objective response rate 87%). CONCLUSIONS: The combination of cisplatin with cetuximab and HART is active, well tolerated and merits additional investigation. The recommended weekly dose of cisplatin for phase II studies is 40 mg/m².

Head and neck in situ carcinoma: survival analysis of the Thuringian cancer registration database.

Head and neck in situ carcinoma is seldom diagnosed. Our knowledge about in situ cancer is limited. This study describes the epidemiology and prognosis of head and neck in situ cancer in Thuringia, Germany. We analyzed the cancer data of the Thuringian cancer registry database from 1996 to 2005. The database contained 3821 patients with primary head and neck cancer. Thirty-four patients (0.88%) had an in situ carcinoma. They were evaluated for patient's characteristics, tumor stage, incidence, treatment and trends in overall survival (OS) and recurrence-free survival (RFS). During 1996-2005, the average annual incidence of head and neck in situ carcinoma was 0.14 per 100,000 persons. Half of the cases were localized in the larynx. The patients were treated by local excision. Six patients (18%) developed a local recurrence. Only one recurrent tumor was diagnosed in early stage (rT1), but the other five tumors in advanced stage (rT3/rT4). The median time to recurrence was 27.43 months. For all 34 patients with in situ carcinoma, the 5-year OS was 84% and the 5-year RFS 60.4%. OS was better for laryngeal in situ cancer than for oral cavity or pharyngeal in situ cancer (p=0.031). The surveillance of patients with head and neck in situ carcinoma after treatment should be performed like in patients with invasive cancer, because nearly one fifth of patients developed a recurrence, predominantly in advanced stage.

Auditory stream segregation in children with Asperger syndrome.

Individuals with Asperger syndrome (AS) often have difficulties in perceiving speech in noisy environments. The present study investigated whether this might be explained by deficient auditory stream segregation ability, that is, by a more basic difficulty in separating simultaneous sound sources from each other. To this end, auditory event-related brain potentials were recorded from a group of school-aged children with AS and a group of age-matched controls using a paradigm specifically developed for studying stream segregation. Differences in the amplitudes of ERP components were found between groups only in the stream segregation conditions and not for simple feature discrimination. The results indicated that children with AS have difficulties in segregating concurrent sound streams, which ultimately may contribute to the difficulties in speech-in-noise perception.

Isolation and characterization of microsatellite loci in Pitcairnia albiflos (Bromeliaceae), an endemic bromeliad from the Atlantic Rainforest, and cross-amplification in other species.

Eight microsatellite markers were isolated from Pitcairnia albiflos, an endangered endemic bromeliad species restricted to 'inselberg' rock outcrops in the state of Rio de Janeiro, Brazil. The number of alleles observed for each locus ranged from two to 12. Average observed and expected heterozygosities were 0.408 and 0.663, respectively. The cross-amplification test in 16 taxa suggests that the markers will be useful in numerous related bromeliad species. The loci will be used to study genetic structure and reproductive biology in fragmented inselberg populations and the origin and maintenance of barriers to gene flow between sympatric Pitcairnia species.

Association of DISC1 with autism and Asperger syndrome.

The DISC1 gene at 1q42 has generated considerable interest in various psychiatric diseases, since a balanced translocation interrupting the gene was found to cosegregate with schizophrenia and related mental illnesses in a large Scottish pedigree. To date, linkage and association findings to this locus have been replicated in several study samples ascertained for psychotic disorders. However, the biological function of DISC1 in neuronal development would suggest a potential role for this gene also in other, early onset neuropsychiatric disorders. Here we have addressed the allelic diversity of the DISC1, DISC2 and TRAX genes, clustered in 1q42, in Finnish families ascertained for infantile autism (97 families, n(affected)=138) and Asperger syndrome (29 families, n(affected)=143). We established association between autism and a DISC1 intragenic microsatellite (D1S2709; P=0.004). In addition, evidence for association to Asperger syndrome was observed with an intragenic single nucleotide polymorphism (SNP) of DISC1 (rs1322784; P=0.0058), as well as with a three-SNP haplotype (P=0.0013) overlapping the HEP3 haplotype, that was previously observed to associate with schizophrenia in Finnish families. The strongest associations were obtained with broad diagnostic categories for both disorders and with affected males only, in agreement with the previous sex-dependent effects reported for DISC1. These results would further support the involvement of DISC1 gene also in the etiopathogenesis of early onset neuropsychiatric disorders.

[Epidural anesthesia for coronary revascularization in the conscious patient]. / Revascularización coronaria en el paciente despierto bajo anestesia epidural.

Thoracic epidural anesthesia has been widely used to complement general anesthesia in coronary artery bypass grafting. The main advantages of the combination are excellent pain control and a less pronounced stress response to surgery. The invasiveness of surgery to treat ischemic heart disease has been attenuated thanks to the use of the mini-sternotomy and coronary anastomosis without extracorporeal circulation. In 4 patients, coronary artery revascularization was carried out via a mini-sternotomy, grafting the anterior descending artery to the left internal thoracic artery under high thoracic epidural anesthesia (block of segments T1-T8) with a perfusion of 0.75% ropivacaine and fentanyl in a conscious patient. There were no hemodynamic or respiratory complications during surgery. The mean duration of stay in the intensive care unit was less than 18 hours and the mean hospital stay was less than 5 days. Postoperative coronary arteriograms demonstrated the patency of all grafts and all patients were asymptomatic at 1 month. Our initial experience suggests that the use of only high thoracic epidural anesthesia is feasible in coronary revascularization in selected, cooperative patients who require a single coronary bypass graft.

Revascularización coronaria en el paciente despierto bajo anestesia epidural / Epidural anesthesia for coronary revascularization in the conscious patient

La anestesia epidural torácica ha sido ampliamenteutilizada en cirugía cardiaca como coadyuvante a laanestesia general en pacientes intervenidos de revascularizacióncoronaria. Sus principales ventajas son el excelentecontrol del dolor postoperatorio y la disminuciónde la respuesta al estrés quirúrgico. En el tratamientoquirúrgico de la cardiopatía isquémica la agresión quirúrgicase ha atenuado al reducir del tamaño de la esternotomíay a la realización de las anastomosis coronariassin circuito de circulación extracorpórea.Se han intervenido 4 pacientes de revascularizacióncoronaria a través de mini-esternotomía, revascularizandola arteria descendente anterior con la arteria mamariaizquierda, bajo anestesia epidural torácica alta (bloqueosegmentario T1-T8) con perfusión de ropivacaína0,75% y fentanilo y con el paciente consciente. No hubocomplicaciones hemodinámicas, ni respiratorias durantela cirugía. El tiempo medio de estancia en CuidadosIntensivos fue menor de 18 horas y la estancia mediahospitalaria menor de 5 días. La coronariografía postoperatoriamostró permeabilidad de los injertos en todoslos casos y los 4 pacientes permanecieron asintomáticosal mes.CONCLUSIÓN: Nuestra experiencia inicial indica que eluso exclusivo de la epidural torácica alta para la revascularizacióncoronaria sin circuito de circulación extracorpórea,supone una opción en pacientes seleccionados,colaboradores y que precisen revascularización coronariade un solo vaso

Thoracic epidural anesthesia has been widely used to complement general anesthesia in coronary artery bypass grafting. The main advantages of the combination are excellent pain control and a less pronounced stress response to surgery. The invasiveness of surgery to treat ischemic heart disease has been attenuated thanks to the use of the mini-sternotomy and coronary anastomosis without extracorporeal circulation. In 4 patients, coronary artery revascularization was carried out via a mini-sternotomy, grafting the anterior descending artery to the left internal thoracic artery under high thoracic epidural anesthesia (block of segments T1-T8) with a perfusion of 0.75% ropivacaine and fentanyl in a conscious patient. There were no hemodynamic or respiratory complications during surgery. The mean duration of stay in the intensive care unit was less than 18 hours and the mean hospital stay was less than 5 days. Postoperative coronary arteriograms demonstrated the patency of all grafts and all patients were asymptomatic at 1 month. Our initial experience suggests that the use of only high thoracic epidural anesthesia is feasible in coronary revascularization in selected, cooperative patients who require a single coronary bypass graft

Atypical pattern of discriminating sound features in adults with Asperger syndrome as reflected by the mismatch negativity.

Asperger syndrome, which belongs to the autistic spectrum of disorders, is characterized by deficits of social interaction and abnormal perception, like hypo- or hypersensitivity in reacting to sounds and discriminating certain sound features. We determined auditory feature discrimination in adults with Asperger syndrome with the mismatch negativity (MMN), a neural response which is an index of cortical change detection. We recorded MMN for five different sound features (duration, frequency, intensity, location, and gap). Our results suggest hypersensitive auditory change detection in Asperger syndrome, as reflected in the enhanced MMN for deviant sounds with a gap or shorter duration, and speeded MMN elicitation for frequency changes.

Auditory perception and attention as reflected by the brain event-related potentials in children with Asperger syndrome.

OBJECTIVE: Language development is delayed and deviant in individuals with autism, but proceeds quite normally in those with Asperger syndrome (AS). We investigated auditory-discrimination and orienting in children with AS using an event-related potential (ERP) paradigm that was previously applied to children with autism. METHODS: ERPs were measured to pitch, duration, and phonetic changes in vowels and to corresponding changes in non-speech sounds. Active sound discrimination was evaluated with a sound-identification task. RESULTS: The mismatch negativity (MMN), indexing sound-discrimination accuracy, showed right-hemisphere dominance in the AS group, but not in the controls. Furthermore, the children with AS had diminished MMN-amplitudes and decreased hit rates for duration changes. In contrast, their MMN to speech pitch changes was parietally enhanced. The P3a, reflecting involuntary orienting to changes, was diminished in the children with AS for speech pitch and phoneme changes, but not for the corresponding non-speech changes. CONCLUSIONS: The children with AS differ from controls with respect to their sound-discrimination and orienting abilities. SIGNIFICANCE: The results of the children with AS are relatively similar to those earlier obtained from children with autism using the same paradigm, although these clinical groups differ markedly in their language development.

Postprandial mononuclear NF-kappaB activation is independent of the AGE-content of a single meal.

OBJECTIVE: Dietary uptake of Advanced Glycation Endproducts (AGE) is supposed to potentially contribute to inflammatory reactions linked to vascular dysfunction and late diabetic complications. One mechanism by which dietary AGE might exert these effects is by activation of the proinflammatory transcription factor NF-kappa-B. The aim of this study was to analyze the postprandial effects of a casein meal with low or high AGE content on postprandial NF-kappaB activation in peripheral blood mononuclear cells (pBMC) of healthy volunteers. RESEARCH DESIGN AND METHODS: Casein was heated for 40 h at 50 degrees C in the presence of sorbitol or glucose, resulting in either minimal (Sorbitol [S]-casein) or large (glucose [G]-casein) amounts of AGE-modified casein. Nine healthy volunteers ate 250 g of both types of casein, whereas both meals were separated at least by 2 weeks. Plasma and pBMC were taken before and 2 h after each meal. Thereafter, the defined AGE carboxymethyllysine (CML) was determined by ELISA and Western blot. NF-kappaB activation in pBMC was assayed using Electrophoretic Mobility Shift Assays (EMSA) and Western blot analysis. RESULTS: S-casein contained only minor amounts of CML and no pentosidine, while G-casein contained large amounts of both. 2 h after ingestion, the S-casein or the G-casein-meal, both, resulted in a non-significant increase in plasma CML and in the intracellular CML-content of pBMC. This was paralleled by a highly significant increase in postprandial mononuclear NF-kappaB-binding activity. Remarkably, neither the extent of NF-kappaB induction (178% for S-casein, 188% for G-casein), nor composition of the NF-kappaB heterodimer (mainly consisting of NF-kappaB p50/p65) were significantly different after intake of S-casein or G-casein. Consistently, Western blots confirmed an increased NF-kappaBp65 nuclear translocation and a decrease of NF-kappaBp65 in the cytoplasm, while no difference in postprandial NF-kappaB nuclear translocation was observed following intake of S-casein or G-casein. CONCLUSION: Postprandial mononuclear NF-kappaB activation after a single meal is independent of the AGE-content of the ingested protein.