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[Induction of atrial tachyarrhythmia in patients with Wolff-Parkinson-White syndrome with and without spontaneous atrial fibrillation].

The purpose of this study was to examine the relation between spontaneous atrial fibrillation and the induction of atrial tachyarrhythmias during electrophysiologic study in patients with Wolff-Parkinson-White, with and without atrial fibrillation. Intracavitary electrophysiologic study was performed on 115 patients, 27 with spontaneous atrial fibrillation (group 1), 57 symptomatic due to AV re-entrant tachycardias, without spontaneous atrial fibrillation (group 2) and 31 asymptomatic (group 3). Induction of atrial fibrillation was attempted by using single and double atrial extrastimuli during atrial pacing at 2 different cycle lengths and by incremental atrial pacing (protocol A). When atrial fibrillation was not obtained, atrial bursts were added (protocol B). Atrial fibrillation or flutter were induced in 81% of group 1.54% of group 2 and 55% of group 3 patients (p less than 0.05), using protocol A. They were induced in 100, 75 and 71%, respectively (p = 0.01), with protocol B. Considering only sustained (greater than 1 minute) episodes, atrial fibrillation or flutter were induced in the three groups with protocol A in 74, 33 and 32% of the patients, respectively (p less than 0.001). The difference in the three groups was even greater when atrial fibrillation was considered separately from atrial flutter. The reason for this was that atrial fibrillation was induced in two thirds of group 1 patients, while only about 15% of patients without spontaneous atrial fibrillation had this arrhythmia induced. Our results suggest that the induction of sustained atrial fibrillation is a useful parameter to separate Wolff-Parkinson-White patients with from those without spontaneous atrial fibrillation. Due to the low specificity of the analysis of the shortest R-R interval during induced atrial fibrillation for the identification of the patients at risk of sudden death, the induction of sustained atrial fibrillation could be proposed as an additional parameter. This would improve the specificity of electrophysiologic study.

Adult↗

Analysis of a model virus using residue-specific chemical cleavage and MALDI-TOF mass spectrometry.

A nonenzymatic proteomics strategy is applied to the rapid identification of viruses. The approach provides solubilization and subsequent digestion of viral coat proteins in under 30 s. Acid digestions were carried out using a laboratory-quality microwave system equipped with temperature, pressure, and power controls, which allowed for precise optimization of experimental parameters. Under optimal conditions, this method provides an efficient alternative to traditional enzymatic digestion-based methods for virus identification. Following rapid microwave heating of a suspension of a model virus, RNA bacteriophage MS2, 13 chemical digestion products were detected in parallel with the coat protein precursor using MALDI-TOF MS. Because of the high sequence coverage obtained, the bacteriophage MS2 coat protein was identified with high confidence and the specificity of the identification allowed for the discrimination between bacteriophage MS2 and other closely related RNA bacteriophages.

Amino Acid Sequence↗

Comparison of transesophageal echocardiographic identification of embolic risk markers in patients with lone versus non-lone atrial fibrillation.

Although transesophageal echocardiographically derived parameters, notably spontaneous echocardiographic contrast (SEC) in the left atrium or left atrial appendage (LAA), are known predictors of embolism in atrial fibrillation, their value is less well known in patients who have lone atrial fibrillation (LAF). This study describes transesophageal echocardiographic findings and identifies clinical predictors of SEC in the left atrium or LAA in a cohort of patients who had LAF. Eighty-two patients who had LAF and 289 patients who had non-LAF and underwent transesophageal echocardiography were enrolled from July 1998 to March 2002. LAA abnormality was defined as the presence of an LAA area >5 cm(2), emptying or filling LAA velocities <25 cm/s, or the presence of SEC or thrombus in the left atrium or LAA; LAA abnormalities were significantly less frequent in patients who had LAF than in those who had non-LAF. SEC in the left atrium or LAA was significantly less frequent in patients who had LAF than in those who had non-LAF (29.3% vs 49.8%, respectively, p <0.001). In patients who had LAF, SEC in the left atrium or LAA was significantly (p <0.05) less frequent in patients who were </=60 years old (17.9%) than in patients who were >60 years old (39.5%) and in patients who had paroxysmal LAF (5.9%) than in those who had persistent LAF (45.8%). On multivariate analysis, age and persistent LAF were the only clinical variables independently associated with SEC. Thus, transesophageal echocardiography detects thromboembolism risk markers in patients who have LAF. These abnormalities are less frequent in patients who have LAF than in those who are at low risk and have non-LAF; however, in patients who have LAF, older age and persistent atrial fibrillation are associated with these risk markers.

Aged↗

Identification of ethanol-intoxicated patients with minor head trauma requiring computed tomography scans.

OBJECTIVE: To determine whether clinical parameters and neurologic scores can be used to guide the decision to obtain computed tomography (CT) head scans for ethanol- intoxicated patients with presumed-minor head injuries. METHODS: In a prospective cohort analysis, 107 consecutive adult patients who presented to a county emergency department (ED) with serum ethanol levels >80 mg/dL and minor head trauma were studied. Commonly used clinical variables were determined for each patient. Each patient also underwent an abbreviated neurologic scoring examination and a Glasgow coma scale (GCS) score evaluation at the time of presentation and one hour later, after which a cranial CT scan was done. For purposes of analysis, patients with and patients without intracerebral injuries visible on CT scans of the head were compared. RESULTS: Nine of 107 patients (8.4%; 95% confidence interval [CI] = 3.9-15.4%) had CT scans that were positive for intracerebral injury. Two patients (1.9%; 95% CI = 0.2-6.6%) needed craniotomy. Five patients had hemotympanum and two patients had bilateral periorbital ecchymosis, but CT scans were negative for intracerebral injury in these patients. There was no statistically significant difference between the patients with and without CT scan abnormalities, based on the clinical variables, the GCS scores, or the abbreviated neurologic scoring examinations at presentation or at one hour. CONCLUSION: The prevalence of intracerebral injury in CT scans of ethanol-intoxicated patients with minor head injuries was 8.4%. Commonly used clinical parameters and neurologic scores at presentation and one hour later were unable to predict which patients would have intracerebral injuries and evidenced by CT scans. Our low (1.9%) neurosurgical intervention rate supports the need to develop a selective approach to CT scanning in this population.

Adult↗

Simultaneous assessment of electrocardiographic parameters for risk stratification: validation in healthy subjects.

BACKGROUND: Sudden cardiac death represents a major public health problem, but in the general population the identification of those subjects at very high risk remains poor. Simultaneous multiparametric ECG analysis can improve the identification of high-risk patients. METHODS: Five-min ECG recordings at a 5 MHz sampling rate (extended length-XL-ECG, Mortara Instruments, Milwaukee, WI, USA) were acquired in 105 healthy subjects (age range 21 to 80 years), equally distributed for age decades and sex, and three additional recordings, 30 min apart, were repeated in 30 subjects on the second day. The following parameters were recorded and analyzed: the RR interval, QRS duration, QT interval corrected according to the Bazett and Fridericia formulae, QT dispersion, T wave complexity, activation-recovery interval dispersion, standard deviation of the RR intervals, filtered QRS duration, the square root of the mean voltage of the last 40 ms of the filtered QRS, and the length of time that the terminal vector magnitude complex remains < 40 microV. RESULTS: QRS duration, activation-recovery interval dispersion, and filtered QRS differed in the two sexes. The standard deviation of the RR intervals, T wave complexity and QT dispersion were significantly correlated with age. The reproducibility was good for each parameter. CONCLUSIONS: The XL-ECG allows the simultaneous calculation of eight adequately reproducible different parameters the values of which are in agreement with those of the literature. Thus, XL-ECG is a reliable time- and cost-saving tool.

Adult↗

Lack of association between dyslipidemia and insulin resistance in HIV-infected persons treated with highly active antiretroviral therapy.

OBJECTIVE: Highly active antiretroviral therapy has been implicated in the development of metabolic toxicities, including insulin resistance. Because it is "clinically silent," insulin resistance is often undetected, thus precluding the initiation of treatments that may prevent progression to frank diabetes. Previous studies have documented associations between dyslipidemic profiles and insulin resistance in patients who do not have the human immunodeficiency virus (HIV). Therefore, we explored whether serum lipids, parameters that are routinely measured in patients who have HIV or the acquired immunodeficiency syndrome, could be used to facilitate the identification of insulin resistance in patients infected with HIV. METHODS: Thirty-three adult patients who had clinically stable HIV infection and treated with highly active antiretroviral therapy fasted overnight and underwent phlebotomy to measure the following parameters: insulin levels, blood glucose, triacylglycerols, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol. RESULTS: Of the 33 participants, 15 had dyslipidemia, defined according to Adult Treatment Panel (ATP) III criteria, and 18 did not have dyslipidemia. The two groups did not differ significantly with respect to mean fasting insulin levels (P = 0.68). Only two participants had insulin levels that were higher than the laboratory reference range. No significant correlations were found between fasting insulin levels and any lipid parameters. CONCLUSIONS: Serum lipids are not predictive of fasting insulin levels in adult patients who are treated with highly active antiretroviral therapy. The findings are limited by the low prevalence of insulin resistance in the study sample and the small sample size.

Adolescent↗

Search for unknown adducts: increase of sensitivity through preselection by biochemical parameters.

Electrophilically reactive compounds or metabolites that occur in humans can be monitored through their reaction products with proteins and DNA. The identification of genotoxic risk factors, e.g., by haemoglobin (Hb) adducts, comprises both the identification of the causative factor and an estimate of the contribution to risk. The problems involved are illustrated by efforts to trace the origin of the observed background hydroxyethylations in Hb from persons without occupational exposures. Earlier work showed influences of smoking and, in animal studies, of dietary fat and intestinal flora on the levels of hydroxyethyl adducts to N-terminal valine. Efforts to measure adducts originating from ethene in environmental tobacco smoke and urban air show, however, that the resolving power of the methods used for identifying unknown risk factors must be increased. Studies of groups with excessive living habits and biochemical parameters that favour higher tissue doses of electrophiles would also enhance the possibilities of identifying risk factors.

Alkylation↗

Decomposition of nonlinear non-Gaussian process and its application to nonlinear filter and predictor design.

An approach for decomposing of a Nonlinear Non-Gaussian Process (NNGP) is presented. A set of adjoin processes alpha's are first constructed based on the orthogonal principle so that the linear and nonlinear part of the process can be completely separated by a correlation operation without the statistical assumption on the process (i.e., it is not necessarily a Gaussian Process). The linear and nonlinear filters or predictors can then be designed and implemented independently and the consistency of parameters is guaranteed. An algorithm is given for a second order nonlinear process, and it can easily be extended to higher order cases if necessary. The method is first demonstrated by applying it to a nonlinear filter design problem, i.e., system identification. Finally, the necessity of a proposed decomposition procedure is proven by applying it to an example in which the parameters of a signal model are extracted from a version which is distorted due to the nonlinearity of the channel.

Algorithms↗

Identification and quantification of the plasma volume expander dextran in human urine by liquid chromatography-tandem mass spectrometry of enzymatically derived isomaltose.

Plasma volume expanders are used in sports in order to control haematological parameters and/or to mask erythropoietin (EPO) misuse. A reliable method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for doping control purposes, enabling the identification and quantification of the plasma volume expander dextran in human urine. The dextran polymer was enzymatically hydrolysed by alpha-1,6-glucosidase (dextranase) followed by acetylation of the generated isomaltose subunits, allowing the chromatographic separation of different disaccharides, such as lactose, saccharose and isomaltose, as well as the identification and quantification of the analyte in human urine. The method was used to determine the basal concentration of isomaltose resulting from the enzymatic hydrolysis of polymeric 1,6-linked glucose in 238 routine doping control samples. In addition the concentration of dextran measured as isomaltose was estimated in seven urine specimens obtained from patients treated with dextran. Calibration curves for dextran were linear and reproducible. The inter- and intra-assay coefficients of variation for dextran ranged from 4.9 to 7.3% at three concentration levels between 53 and 1186 microg/mL. Recovery ranged from 97 to 112% (mean 106.9%). The assay limit of detection was 3.8 microg/mL and the lower limit of quantification was 12.5 microg/mL. In 96% of the investigated doping control samples, the concentrations of isomaltose were below the LLOQ of 12.5 microg/mL. Even the highest concentrations were approximately 100-300-fold lower than concentrations found in urine samples of patients after intravenous application of dextran. The presented results demonstrate the capability and reliability of the developed LC-MS/MS method for the identification and quantification of dextran in human urine and can be regarded as a method revealing the misuse of dextran in sports.

Aged↗

Increasing peptide identification in tandem mass spectrometry through automatic function switching optimization.

Comprehensive proteomic studies that employ MS directed peptide sequencing are limited by optimal peptide separation and MS and tandem MS data acquisition routines. To identify the optimal parameters for data acquisition, we developed a system that models the automatic function switching behavior of a mass spectrometer using an MS-only dataset. Simulations were conducted to characterize the number and the quality of simulated fragmentation as a function of the data acquisition routines and used to construct operating curves defining tandem mass spectra quality and the number of peptides fragmented. Results demonstrated that one could optimize for quality or quantity, with the number of peptides fragmented decreasing as quality increased. The predicted optimal operating curve indicated that significant improvements can be realized by selecting the appropriate data acquisition parameters. The simulation results were confirmed experimentally by testing 10 LC MS/MS data acquisition parameter sets on an LC-Q-TOF-MS. Database matching of the experimental fragmentation returned peptide scores consistent with the predictions of the model. The results of the simulations of mass spectrometer data acquisition routines reveal an inverse relationship between the quality and the quantity of peptide identifications and predict an optimal operating curve that can be used to select an optimal data acquisition parameter for a given (or any) sample.

Algorithms↗

Particle detection, number estimation, and feature measurement in gene transfer studies: optical fractionator stereology integrated with digital image processing and analysis.

Assessing the efficacy of in vivo gene transfer often requires a quantitative determination of the number, size, shape, or histological visualization characteristics of biological objects. The optical fractionator has become a choice stereological method for estimating the number of objects, such as neurons, in a structure, such as a brain subregion. Digital image processing and analytic methods can increase detection sensitivity and quantify structural and/or spectral features located in histological specimens. We describe a hardware and software system that we have developed for conducting the optical fractionator process. A microscope equipped with a video camera and motorized stage and focus controls is interfaced with a desktop computer. The computer contains a combination live video/computer graphics adapter with a video frame grabber and controls the stage, focus, and video via a commercial imaging software package. Specialized macro programs have been constructed with this software to execute command sequences requisite to the optical fractionator method: defining regions of interest, positioning specimens in a systematic uniform random manner, and stepping through known volumes of tissue for interactive object identification (optical dissectors). The system affords the flexibility to work with count regions that exceed the microscope image field size at low magnifications and to adjust the parameters of the fractionator sampling to best match the demands of particular specimens and object types. Digital image processing can be used to facilitate object detection and identification, and objects that meet criteria for counting can be analyzed for a variety of morphometric and optical properties.

Cell Count↗

[Nonlinear analysis of epileptic multichannel EEG].

OBJECTIVE: To study the difference between the nonlinear eigenvalue of epileptic patients and normal subjects for accurate identification of epileptic EEG signal. METHODS: Multivariable phase space reconstruction technique was employed to analyze the EEG of epileptic patients for estimating the correlation dimension(D(2)), which was one of the most often used parameters in quantitative discretion of complicated nonlinear dynamics system. RESULT AND CONCLUSION: The correlation dimension is an important eigenvalue for epileptic EEG identification.

Electroencephalography↗

Optimization of reversed-phase microcapillary liquid chromatography for quantitative proteomics.

Currently, the field of shotgun proteomics relies primarily on the separation of peptides by reversed-phase microcapillary chromatography (RP-microLC) combined with either electrospray ionization (ESI) or matrix-assisted laser desorption ionization (MALDI) and tandem mass spectrometry (MS/MS) for protein identification as well as quantification. For this purpose we herein describe construction of a RP-microLC-ESI column-emitter along with optimized microLC conditions for using the device to quantify pair-wise changes in protein expression via the isotope coded affinity tag (ICAT) method that also maximize peak capacity. These optimized RP-microLC parameters required a balance be reached between the disparate needs of quantification which requires good peak shape and identification (i.e. proteome coverage) of proteins via peptide collision induced dissociation (CID) which requires peak capacity be maximized. A complex biological sample from a study of murine acetaminophen toxicity in hepatocyes was chosen for method development because of the high level complexity, but the biological results are not the focus of this manuscript.

Amino Acid Sequence↗

A confirmation analysis method for identification of chromosomal fragile sites.

Fragile sites are chromosome bands that do not manifest a presumed breakage pattern. Identification of fragile sites is a way to investigate the mechanism of carcinogenesis because the fragility at a specific chromosome position may be the causation of an associated cancer. A problem in the identification of fragile sites is the high false positive rate arising from simultaneously carrying out a large number of significance tests. To control it, we propose to find a reference study to confirm the identification result of an objective study. We utilize the Bayesian concept for linking two studies. Basically, our method demonstrates a conservative way to take account of the prior information of a binomial parameter. The derived estimate of breakage probability can be interpreted as a resampling weighted sample-pooling method. It is applied to confirm the identification of fragile sites for a data set of neuroblastoma patients.

Chromosome Banding↗

Cerebellum and speech perception: a functional magnetic resonance imaging study.

A variety of data indicate that the cerebellum participates in perceptual tasks requiring the precise representation of temporal information. Access to the word form of a lexical item requires, among other functions, the processing of durational parameters of verbal utterances. Therefore, cerebellar dysfunctions must be expected to impair word recognition. In order to specify the topography of the assumed cerebellar speech perception mechanism, a functional magnetic resonance imaging study was performed using the German lexical items "Boden" ([bodn], Engl. "floor") and "Boten" ([botn], "messengers") as test materials. The contrast in sound structure of these two lexical items can be signaled either by the length of the wordmedial pause (closure time, CLT; an exclusively temporal measure) or by the aspiration noise of wordmedial "d" or "t" (voice onset time, VOT; an intrasegmental cue). A previous study found bilateral cerebellar disorders to compromise word recognition based on CLT whereas the encoding of VOT remained unimpaired. In the present study, two series of "Boden - Boten" utterances were resynthesized, systematically varying either in CLT or VOT. Subjects had to identify both words "Boden" and "Boten" by analysis of either the durational parameter CLT or the VOT aspiration segment. In a subtraction design, CLT categorization as compared to VOT identification (CLT - VOT) yielded a significant hemodynamic response of the right cerebellar hemisphere (neocerebellum Crus I) and the frontal lobe (anterior to Broca's area). The reversed contrast ( VOT - CLT) resulted in a single activation cluster located at the level of the supratemporal plane of the dominant hemisphere. These findings provide first evidence for a distinct contribution of the right cerebellar hemisphere to speech perception in terms of encoding of durational parameters of verbal utterances. Verbal working memory tasks, lexical response selection, and auditory imagery of word strings have been reported to elicit activation clusters of a similar location. Conceivably, representation of the temporal structure of speech sound sequences represents the common denominator of cerebellar participation in cognitive tasks acting on a phonetic code.

Acoustic Stimulation↗

Functional and clinical consequences of mutations in the FSH receptor.

The follicle-stimulating hormone (FSH) is essential for normal gametogenesis. In females FSH is required for ovarian development and follicle maturation whereas in males FSH determines Sertoli cell number and quantitatively and qualitatively normal spermatogenesis. FSH action is mediated by a G-protein coupled receptor expressed solely in granulosa and Sertoli cells. The FSH-receptor (FSHR) gene is localized on chromosome 2 p21 and spans a region of 54 kb. It consists of ten exons; exon one to nine encode the large extracellular domain and the transmembrane domain is comprised of exon ten. Mutations in the FSHR gene could severely affect gametogenesis and result in infertility. Therefore screening programs have been initiated, in which patients with disturbed fertility were searched for mutations in the FSHR gene. Several Finnish families were identified displaying an inherited pattern of ovarian dysgenesis, a disease leading to streaky underdeveloped ovaries and primary amenorrhea. By genetic linkage the locus of the genetic defect was confined to chromosome 2 p21. Analysis of the FSHR gene resulted in the identification of a mutation (Ala189Val) homozygous in all affected females. Functional studies revealed that the mutation affects the proper protein folding and thereby inactivates the receptor. In a male patient hypophysectomized because of a pituitary tumor, who despite undetectable serum gonadotropins had normal semen parameters, we hypothesized an activating mutation of the FSHR. Screening of exon ten of the FSHR gene resulted in the identification of a Asp567Gly transition in the third intracytoplasmatic loop. Functional studies resulted in a 1.5-fold increase in basal cAMP production compared to wild type FSHR, indicating that the heterozygous mutation leads to a ligand-independent constitutive activation of the FSHR. This patient provides an exceptional model of nature defining the role of FSH in human spermatogenesis. Mutations of the FSHR might have differential effects in each gender. For example activating mutations have not been described in women, therefore it is not clear whether the constitutive activity of the receptor could disturb normal follicular development resulting in certain infertility.

Amino Acid Sequence↗

Binocular receptive field models, disparity tuning, and characteristic disparity.

Disparity tuning of visual cells in the brain depends on the structure of their binocular receptive fields (RFs). Freeman and coworkers have found that binocular RFs of a typical simple cell can be quantitatively described by two Gabor functions with the same gaussian envelope but different phase parameters in the sinusoidal modulations (Freeman and Ohzawa 1990). This phase-parameter-based RF description has recently been questioned by Wagner and Frost (1993) based on their identification of a so-called characteristic disparity (CD) in some cells' disparity tuning curves. They concluded that their data favor the traditional binocular RF model, which assumes on overall positional shift between a cell's left and right RFs. Here we set to resolve this issue by studying the dependence of cells' disparity tuning on their underlying RF structures through mathematical analyses and computer simulations. We model the disparity tuning curves in Wagner and Frost's experiments and demonstrate that the mere existence of approximate CDs in real cells cannot be used to distinguish the phase-parameter-based RF description from the traditional position-shift-based RF description. Specifically, we found that model simple cells with either type RF description do not have a CD. Model complex cells with the position-shift-based RF description have a precise CD, and those with the phase-parameter-based RF description have an approximate CD. We also suggest methods for correctly distinguishing the two types of RF descriptions. A hybrid of the two RF models may be required to fit the behavior of some real cells, and we show how to determine the relative contributions of the two RF models.

Animals↗

The identification of bile acid methyl esters by gas chromatography methane chemical ionization mass spectrometry.

Methane chemical ionization mass spectrometric data and gas chromatography retention parameters are reported for 31 bile acid methyl esters. The group includes both saturated and unsaturated compounds with up to three keto or hydroxyl groups. Major ions include the quasimolecular ions and fragments resulting from the loss of neutral species such as methanol, water and methane. The combination of gas-liquid chromatography retention and mass spectral data is sufficient for an unequivocal distinction among all the bile acids studied. Application of this data to the identification of bile acid metabolites is cited.

Bile Acids and Salts↗