Synthesis, characterization and application of a two-fold 13C-labeled calibration standard for the analysis of arsenobetaine using HPLC-ESI-MS/MS without high resolution mass spectrometry.

A procedure has been developed for the determination of arsenobetaine in fish matrix by HPLC-ESI-MS/MS. Hereby (trimethylarsonium)-1,2-(13)C-acetate (arsenobetaine) is used as internal calibration standard. Arsenobetaine was determined in a fish material (Sea Bass) with an expanded uncertainty of 3.8%.

Kramers-Kronig-constrained variational dielectric fitting and the reflectance of a thin film on a substrate.

A test was made of the ability of Kramers-Kronig-constrained variational dielectric fitting to extract the optical conductivity of a thin film from reflectance data containing structure due to both thin film and substrate. The reflectance of a series of well-characterized thin films of SrRu(x)Mg(1-x)O(3) and SrRu(x)O(3) with a variety of thicknesses (approximately 56-300 nm) and dc resistivities (approximately 250-2200 micro Omega cm) was measured. The low frequency values of the extracted optical conductivities agree with the dc measurements, however, removal of features due to the substrate improves with increasing film thickness.

A history of robots: from science fiction to surgical robotics.

Surgical robotics is an evolving field with great advances having been made over the last decade. The origin of robotics was in the science-fiction literature and from there industrial applications, and more recently commercially available, surgical robotic devices have been realized. In this review, we examine the field of robotics from its roots in literature to its development for clinical surgical use. Surgical mills and telerobotic devices are discussed, as are potential future developments.

Cocaine-induced potentiation of synaptic strength in dopamine neurons: behavioral correlates in GluRA(-/-) mice.

Synaptic plasticity in the mesolimbic dopamine (DA) system is thought to contribute to the neural adaptations that mediate behavioral sensitization, a model for core aspects of addiction. Recently, it has been demonstrated that multiple classes of drugs of abuse, as well as acute stress, enhance strength at excitatory synapses on midbrain DA neurons. Here, we show that both the cocaine- and stress-induced synaptic enhancement involves an up-regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. This enhancement requires the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluRA as evidenced by its absence in mice lacking this subunit. The cocaine-elicited, but not the stress-elicited, synaptic potentiation in DA neurons was blocked by a D1-like receptor antagonist, indicating that the in vivo triggering mechanisms differ for these forms of experience-dependent synaptic modification. Surprisingly, behavioral sensitization to cocaine was elicited in GluRA(-/-) mice, indicating that potentiation of excitatory synaptic transmission in DA neurons is not necessary for this form of behavioral plasticity. However, GluRA(-/-) mice did not exhibit a conditioned locomotor response when placed in a context previously paired with cocaine, nor did they exhibit conditioned place preference in response to cocaine. We suggest that the drug-induced enhancement of excitatory synaptic transmission in midbrain DA neurons, although not required for behavioral sensitization per se, may contribute to the attribution of incentive value to drug-associated cues.

Frontal and parietal components of a cerebral network mediating voluntary attention to novel events.

Despite the important role that attending to novel events plays in human behavior, there is limited information about the neuroanatomical underpinnings of this vital activity. This study investigated the relative contributions of the frontal and posterior parietal lobes to the differential processing of novel and target stimuli under an experimental condition in which subjects actively directed attention to novel events. Event-related potentials were recorded from well-matched frontal patients, parietal patients, and non-brain-injured subjects who controlled their viewing duration (by button press) of line drawings that included a frequent, repetitive background stimulus, an infrequent target stimulus, and infrequent, novel visual stimuli. Subjects also responded to target stimuli by pressing a foot pedal. Damage to the frontal cortex resulted in a much greater disruption of response to novel stimuli than to designated targets. Frontal patients exhibited a widely distributed, profound reduction of the novelty P3 response and a marked diminution of the viewing duration of novel events. In contrast, damage to posterior parietal lobes was associated with a substantial reduction of both target P3 and novelty P3 amplitude; however, there was less disruption of the processing of novel than of target stimuli. We conclude that two nodes of the neuroanatomical network for responding to and processing novelty are the prefrontal and posterior parietal regions, which participate in the voluntary allocation of attention to novel events. Injury to this network is indexed by reduced novelty P3 amplitude, which is tightly associated with diminished attention to novel stimuli. The prefrontal cortex may serve as the central node in determining the allocation of attentional resources to novel events, whereas the posterior parietal lobe may provide the neural substrate for the dynamic process of updating one's internal model of the environment to take into account a novel event.

Child abuse and the otolaryngologist: part I.

Nearly 1 million infants and children are neglected and abused yearly in the United States, with a greater than 1% resulting mortality rate. One half of these children are seen by physicians for abuse-related injuries, and nearly 75% have injuries of the head and neck. Physicians, however, account for reporting only 11% of all cases. As experts trained in diseases and injuries of the head and neck, otolaryngologists are particularly well positioned to recognize abuse in the clinic and in the emergency room and during other consultations. We present an overview of child abuse definitions, risk factors, and legal obligations of the physician. We also review the manifestations of child abuse within the head and neck, with particular attention to the role of the otolaryngologist. We briefly discuss some conditions that may be mistaken for abuse and suggest a practical protocol for management of suspected cases in the clinic.

Intermediate length scale dynamics of polyisobutylene.

We report on a neutron spin echo investigation of the intermediate scale dynamics of polyisobutylene studying both the self-motion and the collective motion. The momentum transfer (Q) dependences of the self-correlation times are found to follow a Q(-2/beta) law in agreement with the picture of Gaussian dynamics. In the full Q range of observation, their temperature dependence is weaker than the rheological shift factor. The same is true for the stress relaxation time as seen in sound wave absorption. The collective times show both temperature dependences; at the structure factor peak, they follow the temperature dependence of the viscosity, but below the peak, one finds the stress relaxation behavior.

Assessment of congenital bony nasal obstruction by 3-dimensional CT volume rendering.

The nature and extent of congenital bony nasal obstruction is best determined by X-ray computed tomography (CT) imaging. Three-dimensional volume rendering of CT images provides an integrated perspective that can assist in clinical decision making and in operative planning. Clinical cases of choanal atresia and pyriform aperture stenosis are reviewed with their images. The authors propose this modality as an evolving standard for imaging of congenital bony nasal obstruction.

Is the donut in front of the car? An electrophysiological study examining spatial reference frame processing.

The process of describing an object's location relative to another object results in ambiguity. How do people handle this ambiguity? The present studies examined spatial language processing when use of different reference frames results in ambiguity. We investigated whether electrophysiological (ERP) measures of cognitive processing may elucidate underlying reference frame processing; in particular, we were interested in semantic integration. ERP results showed a larger N400, peaking between 300 and 375 ms, when the intrinsic frame was not used. Behavioural results mirrored this finding, indicating a reduced cognitive processing requirement for the intrinsic reference frame. Previous work has not definitively tied spatial reference frame processing to specific ERP components and their associated cognitive processes. Although the N400 peak seen in this data is early, additional work supports the N400 interpretation, thereby linking spatial frame processing to semantic integration. Results are discussed within the larger context of spatial reference frame processing.

Nucleophilic reactivities of tributylstannyl-substituted furans and thiophenes.

Kinetic investigations of the reactions of benzhydryl cations with stannylated furans and thiophenes suggest that 2-(tributylstannyl)furan and -thiophene are preferentially attacked at the 5-position (k(rel), FcPhCH(+), 20 degrees C, CH(2)Cl(2)).

Pathophysiology underlying diminished attention to novel events in patients with early AD.

BACKGROUND: Patients with mild to moderate AD often are apathetic and fail to attend to novel aspects of their environment. OBJECTIVE: To investigate the mechanisms underlying these changes by studying the novelty P3 response that measures shifts of attention toward novel events. METHODS: While event-related potentials were recorded, mildly impaired AD patients and matched normal controls (NC) viewed line drawings that included a repetitive background stimulus, an infrequent target stimulus, and infrequent novel stimuli. Subjects controlled how long they viewed each stimulus by pressing a button. This served as a measure of their allocation of attention. They also responded to targets by depressing a foot pedal. Patients did not differ from NC in age, education, estimated IQ, or mood but were judged by informants to be more apathetic. RESULTS: P3 amplitude to novel stimuli was significantly smaller for AD patients than NC. However, P3 amplitude to target stimuli did not differ between groups. For NC, P3 response to novel stimuli was much larger than to background stimuli. In contrast, for patients with AD, there was no difference in P3 response to novel vs background stimuli. Although NC spent more time looking at novel than background stimuli, patients with AD distributed their viewing time evenly. Remarkably, for patients with AD, the amplitude of the novelty P3 response powerfully predicted how long they would spend looking at novel stimuli (R2 = 0.52) and inversely correlated with apathy severity. CONCLUSIONS: The decreased attention to novel events exhibited by patients with AD cannot be explained by a nonspecific reduction in their attentional abilities. The novelty P3 response is markedly diminished in mild AD, at a time when the target P3 response is preserved. The disruption of the novelty P3 response predicts diminished attention to novel stimuli and is associated with the apathy exhibited by patients with AD.

Protein kinase CK2 signal in neoplasia.

Protein kinase CK2 (previously known as casein kinase II) is a protein serine/threonine kinase that has been implicated in cell growth and proliferation. The focus of this review is on the apparent role of CK2 in cancer. Studies from several laboratories have shown a dysregulated expression of the kinase in tumors. Nuclear matrix and chromatin appear to be key sites for signaling of the CK2 activity in relation to cell growth. Several types of growth stimuli produce a common downstream response in CK2 by enhancing its nuclear shuttling. The neoplastic change is also associated with changes in intracellular localization of the kinase so that a higher nuclear localization is observed in tumor cells compared with normal cells. Experimental studies suggest that dysregulated expression of the alpha subunit of CK2 imparts an oncogenic potential in the cells such that in cooperation with certain oncogenes it produces a profound enhancement of the tumor phenotype. Recent studies have provided evidence that overexpression of CK2 in tumor cells is not simply a reflection of tumor cell proliferation alone but additionally may reflect the pathobiological characteristics of the tumor. Of considerable interest is the possibility that CK2 dysregulation in tumors may influence the apoptotic activity in those cells. Approaches to interfering with the CK2 signal may provide a useful means for inducing tumor cell death.

The effect of changing transfusion practice on rates of perioperative stroke and myocardial infarction in patients undergoing carotid endarterectomy: a retrospective analysis of 1114 Mayo Clinic patients. Mayo Perioperative Outcomes Group.

OBJECTIVE: To evaluate changes in the institution's red blood cell (RBC) transfusion practice during the past 15 years and the influence of these changes on neurologic or cardiac morbidity after carotid endarterectomy. PATIENTS AND METHODS: Based on a retrospective analysis of the Mayo Clinic database, 1,114 patients who underwent carotid endarterectomy were stratified into 1 of 2 groups: (1) 1980 to 1985 (ie, pre-human immunodeficiency virus screening, early-practice group [n=552]) and (2) 1990 to 1995 (ie, recent-practice group [n=562]). Data were compared between time periods using the chi2 test for categorical variables and the rank sum test for continuous variables. Logistic regression was used to assess the association between perioperative transfusion practice and the occurrence of stroke or myocardial infarction. Two-tailed P values < or = 05 were considered statistically significant. RESULTS: Patients in the recent-practice group were significantly older (mean +/- SD age, 69.6 +/- 8.7 years) vs 65.9 +/- 8.3 years in the early-practice group (P<.001). The proportion of patients receiving perioperative RBC transfusion decreased dramatically from 72.9% in 1980-1985 to 8.7% in 1990-1995 (P<.001). Additionally, the mean +/- SD number of RBC units transfused decreased from 1.10 +/- 1.30 U in 1980-1985 to 0.27 +/- 1.22 U in 1990-1995 (P<.001). Mean +/- SD discharge hemoglobin concentration decreased from 13.7 +/- 1.4 g/dL in 1980-1985 to 11.8 +/- 1.5 g/dL in 1990-1995 (P<.001). Rates of perioperative stroke and myocardial infarction did not differ between the 2 time periods (early-practice group vs recent-practice group: stroke, 5.1% vs 3.6% [P=.22]; myocardial infarction, 1.5% vs 2.3% [P=.29]). CONCLUSIONS: Our results suggest that elderly patients undergoing carotid endarterectomy (ie, individuals known to be at high risk for cerebral and cardiac ischemia) can tolerate modest perioperative anemia despite a considerable change in the institution's transfusion practice (lower "transfusion trigger," the hemoglobin concentration or hematocrit value below which RBC transfusion is indicated).

Securing cochlear implants to the skull: two alternate methods.

In view of the various problems encountered with the traditional methods of securing cochlear implants--including dural tear and suture dissolution following infection--we devised two alternate methods of performing this procedure. We use a titanium mesh or a Gore-Tex patch secured with two 4-mm screws to fix the receiver to the skull. No patient who has undergone either of these procedures at our institution has experienced any of the complications that are associated with the older silk, nylon, and Dacron sutures. Moreover, our two alternate methods are less technically difficult and can be performed in a shorter period of time.

A unique case of Bezold's abscess associated with multiple dural sinus thromboses.

OBJECTIVES/HYPOTHESIS: Bezold's abscess and dural sinus thromboses are rare complications of otitis media in the era of antibiotics. Although potentially fatal, they are treatable. We present a unique case report of Bezold's abscess in association with multiple dural sinus thromboses. STUDY DESIGN: Single case report. METHODS: A young female patient's clinical course is presented and discussed. We review the anatomy, incidence, pathogenesis, and treatment of Bezold's abscess and dural sinus thrombosis. RESULTS: After mastoidectomy, neck exploration, broad-spectrum intravenous antibiotics, and anticoagulation therapy, the patient recovered fully and has remained asymptomatic since her discharge from the hospital at 12 months' follow-up. CONCLUSIONS: This is the first reported case of Bezold's abscess associated with a cavernous sinus thrombosis and the third reported case of Bezold's abscess associated with lateral sinus thrombosis. Despite its rarity, Bezold's abscess must be recognized and treated aggressively. Dural sinus thrombosis is relatively more common, and treatment of the underlying cause is essential. The diagnosis and rapid, aggressive treatment of these conditions are essential for an optimal clinical outcome.

Real-time, cine magnetic resonance imaging for evaluation of the pediatric airway.

BACKGROUND: Standard magnetic resonance imaging (MRI) and computed tomographic (CT) modalities are limited in their ability to image dynamic organs. New real-time, dynamic, cine magnetic resonance imaging (CMRI) techniques have the potential to image moving structures. OBJECTIVE: We therefore investigated the feasibility of using CMRI techniques to dynamically image the human airway, to assess laryngeal and tracheal patency and function. METHODS: A cohort of 10 pediatric patients, 10 adult patients, and 10 normal volunteers underwent routine static MRI, as well as CMRI using a Siemens 1.5 T Vision system (Siemens, Erlangen, Germany). Patients also underwent endoscopic evaluation. Cine axial, coronal, and sagittal sequences of the larynx and trachea were obtained during quiet respiration, as well as during a variety of provocative maneuvers. RESULTS: CMRI readily demonstrated normal vocal cord mobility and tracheal stability in normal volunteers. Abnormal vocal mobility was easily appreciated using the CMRI imaging system. Similarly, dynamic effects of tracheomalacia were clearly demonstrated using CMRI. Dynamic extrinsic tracheal compression resulting from mass lesions or anomalous vasculature was also visualized using CMRI. CONCLUSIONS: Cine MRI of the airway has the potential to provide novel data regarding laryngeal and tracheal patency and function. This evolving modality may serve as a valuable adjunct to static MR and CT imaging, as well as endoscopy, in the assessment of the airway.

An electrophysiological index of stimulus unfamiliarity.

This study investigated the functional significance of the N2 response to novel stimuli. In one condition, background, target, and deviant stimuli were simple geometric figures. In a second condition, all stimulus types were unfamiliar/unusual figures. In a third condition, background and target stimuli were unusual figures and deviant stimuli were simple shapes. Unusual figures, whether they were deviant, target, or background stimuli, evoked larger N2 responses than their simple, familiar counterparts. N2 elicited by an unusual background stimulus was larger than that evoked by simple, deviant stimuli, a pattern opposite that exhibited by the subsequent P3. Deviance from immediate context had limited influence over N2 amplitude. The results suggest that novelty N2 and novelty P3 reflect the processing of different aspects of "novel" visual stimuli. The novelty P3 is particularly sensitive to deviation from immediate context. In contrast, the novelty N2 is sensitive to deviation from long-term context that renders a stimulus unfamiliar and difficult to encode.

The influence of stimulus deviance on electrophysiologic and behavioral responses to novel events.

This study investigated the role of stimulus deviance in determining electrophysiologic and behavioral responses to "novelty." Stimulus deviance was defined in terms of differences either from the immediately preceding context or from long-term experience. Subjects participated in a visual event-related potential (ERP) experiment, in which they controlled the duration of stimulus viewing with a button press, which served as a measure of exploratory behavior. Each of the three experimental conditions included a frequent repetitive background stimulus and infrequent stimuli that deviated from the background stimulus. In one condition, both background and deviant stimuli were simple, easily recognizable geometric figures. In another condition, both background and deviant stimuli were unusual/unfamiliar figures, and in a third condition, the background stimulus was a highly unusual figure, and the deviant stimuli were simple, geometric shapes. Deviant stimuli elicited larger N2-P3 amplitudes and longer viewing durations than the repetitive background stimulus, even when the deviant stimuli were simple, familiar shapes and the background stimulus was a highly unusual figure. Compared to simple, familiar deviant stimuli, unusual deviant stimuli elicited larger N2-P3 amplitudes and longer viewing times. Within subjects, the deviant stimuli that evoked the largest N2-P3 responses also elicited the longest viewing durations. We conclude that deviance from both immediate context and long-term prior experience contribute to the response to novelty, with the combination generating the largest N2-P3 amplitude and the most sustained attention. The amplitude of the N2-P3 may reflect how much "uncertainty" is evoked by a novel visual stimulus and signal the need for further exploration and cognitive processing.

Antisense oligonucleotides against protein kinase CK2-alpha inhibit growth of squamous cell carcinoma of the head and neck in vitro.

BACKGROUND: Human squamous cell carcinomas of the head and neck (SCCHN) overexpress the protein kinase CK2, and elevated CK2 activity correlates with aggressive tumor behavior and poor clinical outcome. We therefore investigated whether interference with CK2 expression would inhibit SCCHN cell growth in vitro. METHODS: We targeted the catalytic (alpha) subunit of CK2 using an antisense oligodeoxynucleotide (ODN) strategy. Human Ca9-22 cells derived from SCCHN were transfected with CK2-alpha sense, nonsense, or antisense ODN; CK2 activity was measured; and the effect on CK2 activity and on cell growth was determined. RESULTS: Transfection of Ca9-22 cells with antisense CK2-alpha ODN resulted in significantly decreased CK2 kinase activity associated with nuclear chromatin and in dose-dependent growth inhibition of Ca9-22 cells in vitro. CONCLUSIONS: Interference with the protein kinase CK2 signal in SCCHN cells may offer a novel anticancer strategy for this malignancy.