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The Patient State Index as an indicator of the level of hypnosis under general anaesthesia.

BACKGROUND: This retrospective study describes the performance of the Patient State Index (PSI), under standard clinical practice conditions. The PSI is comprised of quantitative features of the EEG (QEEG) that display clear differences between hypnotic states, but consistency across anaesthetic agents within the state. METHODS: The PSI was constructed from a systematic investigation of a database containing QEEG extracted from the analyses of continuous 19 channel EEG recordings obtained in 176 surgical patients. Induction was accomplished with etomidate, propofol, or thiopental. Anaesthesia was maintained by isoflurane, desflurane, or sevoflurane, total i.v. anaesthesia using propofol, or nitrous oxide/narcotics. It was hypothesized that a multivariate algorithm based on such measures of brain state, would vary significantly with changes in hypnotic state. RESULTS: Highly significant differences were found between mean PSI values obtained during the different anaesthetic states selected for study. The relationship between level of awareness and PSI value at different stages of anaesthetic delivery was also evaluated. Regression analysis for prediction of arousal level using PSI was found to be highly significant for the combination of all anaesthetics, and for the individual anaesthetics. CONCLUSIONS: The PSI, based upon derived features of brain electrical activity in the anterior/posterior dimension, significantly co-varies with changes in state under general anaesthesia and can significantly predict the level of arousal in varying stages of anaesthetic delivery.

Adolescent↗

Three-dimensional quantitative analysis of hemispheric asymmetry in the human superior temporal region.

The recent observations of overall symmetry of the caudal infrasylvian region by Steinmetz et al. (1990) and Witelson and Kigar (1991, 1992) diverge from earlier findings of leftward asymmetry in this region (Geschwind and Levitsky, 1968; Galaburda et al., 1987; Larsen et al., 1989). To address this inconsistency, we measured the entire infrasylvian surface posterior to Heschl's gyrus from coronal magnetic resonance images of 10 young, normal, right-handed subjects. Computer models were constructed by tracing contours of this region and then interpolating a 3D triangle mesh between each pair of adjacent contours. Measurements of these models showed no significant directional asymmetry. The same contour set was used to obtain measurements with a conventional algorithm that does not interpolate a surface between contours. The results obtained with the second method showed significant leftward asymmetry. These results suggest that in some cases, unbalanced distortions due to folding differences of the hemispheres are sufficient to obtain spurious findings of left-right asymmetry. This supports the claim of Steinmetz and Witelson that leftward asymmetry is restricted to the temporal bank of the caudal infrasylvian surface, and is balanced by rightward asymmetry of the parietal bank.

Adolescent↗

ACLAME: a CLAssification of Mobile genetic Elements.

The ACLAME database (http://aclame.ulb.ac.be) is a collection and classification of prokaryotic mobile genetic elements (MGEs) from various sources, comprising all known phage genomes, plasmids and transposons. In addition to providing information on the full genomes and genetic entities, it aims to build a comprehensive classification of the functional modules of MGEs at the protein, gene and higher levels. This first version contains a comprehensive classification of 5069 proteins from 119 DNA bacteriophages into over 400 functional families. This classification was produced automatically using TRIBE-MCL, a graph-theory-based Markov clustering algorithm that uses sequence measures as input, and then manually curated. Manual curation was aided by consulting annotations available in public databases retrieved through additional sequence similarity searches using Psi-Blast and Hidden Markov Models. The database is publicly accessible and open to expert volunteers willing to participate in its curation. Its web interface allows browsing as well as querying the classification. The main objectives are to collect and organize in a rational way the complexity inherent to MGEs, to extend and improve the inadequate annotation currently associated with MGEs and to screen known genomes for the validation and discovery of new MGEs.

Bacteriophages↗

Evaluation of the effects of high dose irradiation on canine thigh muscle by follow-up magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: The authors investigate alterations of proton T1 and T2 relaxation times and phosphorus metabolites of canine thigh muscle tissue after high dose x-ray irradiation by follow-up magnetic resonance imaging (MRI) and phosphorus-31 (31P) magnetic resonance spectroscopy (MRS). METHODS: A group of 20 dogs was used for MRI and in vivo 31P MRS. Single doses of 5,000 and 10,000 cGy were delivered to the right thigh muscle of groups of 10 dogs each. All MRI and 31P MRS examinations were performed before irradiation and 1, 7, 14, 28, 42, and 56 days after irradiation. For measurement of T1, repetition time (TR) was measured at 300, 500, 1000, 1500, 2000 msec and echo time (TE) was fixed at 12 msec. Also, for measurement of T2, TE was measured at 20, 40, 60, and 80 msec and TR was fixed at 2000 msec. Image selected in vivo spectroscopy (ISIS) pulse sequence was used to obtain 31P MR spectra. Peak areas for each phosphorus metabolite were measured using a Marquart algorithm. RESULTS: Magnetic resonance imaging signal began to change at 28 days after a single dose of 10,000 cGy, whereas there was no significant MRI signal change until 56 days after a single dose of 5,000 cGy. Also, extensive MRI signal changes were observed at 42 days after a single dose of 10,000 cGy. Significant correlation was established between T2 and a lapse of time although there was no correlation between T1 and a lapse of time. T2 value increased substantially corresponding to the time period after x-ray irradiation. Although MR spectral change was not observed until 42 days after a single dose of 5,000 cGy, it began at 14 days after a single dose of 10,000 cGy. And, significant MR spectral changes were observed at 28 and 42 days. Inorganic phosphate and phosphodiesters signal intensities increased while phosphocreatine signal intensity decreased. The pH value was 7.22 +/- 0.05 at control, and 6.98 +/- 0.04 at 42 days after a single dose of 10,000 cGy. CONCLUSIONS: The postirradiation follow-up MRI and 31P MRS studies demonstrated that morphologic and metabolic changes were dependent upon the x-ray dose and a lapse of time.

Animals↗

A case-mix classification system for medical rehabilitation.

Dissatisfaction with Medicare's current system of paying for rehabilitation care has led to proposals for a rehabilitation prospective payment system, but first a classification system for rehabilitation patients must be created. Data for 36,980 patients admitted to and discharged from 125 rehabilitation facilities between January 1, 1990, and April 19, 1991, were provided by the Uniform Data System for Medical Rehabilitation. Classification rules were formed using clinical judgment and a recursive partitioning algorithm. The Functional Independence Measure version of the Function Related Groups (FIM-FRGs) uses four predictor variables: diagnosis leading to disability, admission scores for motor and cognitive functional status subscales as measured by the Functional Independence Measure, and patient age. The system contains 53 FRGs and explains 31.3% of the variance in the natural logarithm length of stay for patients in a validation sample. The FIM-FRG classification system is conceptually simple and stable when tested on a validation sample. The classification system contains a manageable number of groups, and may represent a solution to the problem of classifying medical rehabilitation patients for payment, facility planning, and research on the outcomes, quality, and cost of rehabilitation.

Activities of Daily Living↗

Objective tinnitus in children.

OBJECTIVE: To discuss the various symptoms and causes of objective tinnitus in children. STUDY DESIGN: Retrospective case review. PATIENTS: Five children who had audible signals emanating from their ears caused by audible spontaneous otoacoustic emissions, palatal myoclonus, arteriovenous malformation, and acoustic trauma. MAIN OUTCOME MEASURE: The tinnitus reported by the patients was linked to acoustic signals that could be measured objectively or heard by the examiner. RESULTS: Four of the five children had essentially normal hearing. The one child who demonstrated a hearing loss audiometrically was thought to have normal hearing sensitivity, but his intense roaring objective tinnitus appeared to mask his low-frequency thresholds. All five patients had measurable acoustic signals in the ear canal that matched the patients' descriptions of their tinnitus. CONCLUSION: The cases illustrate how the objective tinnitus was diagnosed and measured, how a treatment algorithm was applied, and the expected results of treatment. In addition, the cases provide support for the use of psychologic counseling throughout the examination and treatment of objective tinnitus in children.

Adolescent↗

What have we learned about laryngeal physiology from high-speed digital videoendoscopy?

PURPOSE OF REVIEW: The purpose of this review is to describe recent developments in high-speed videoendoscopy. The applications of this technique are highlighted and important findings regarding vocal fold physiology and voice pathology are discussed. RECENT FINDINGS: The number of applications for digital high-speed imaging has increased during recent years because of the development of camera image sensor systems with increased image resolution of video and television quality. Other improvements are related to computer processing speed and storage capacity and the development of automatic algorithms for quantification and measurements both in time and room dimensions. This is enhanced by combining high-speed videoendoscopy with laser-based measurement systems, acoustic analyses or other glottographic methods, such as flow glottography or electroglottography. High-speed videoendoscopy is currently used in studies of voice mechanisms of phonation (e.g., the voice source can be examined with a high sampling rate, from 1000 to over 8000 frames per second), and in phonation onset or offset. High-speed imaging is also useful in linguistic studies and in the examination of different artistic singing styles, such as extremely high-pitched singing, throat singing, or different pop and rock styles. High-speed videoendoscopy is also used in the examination of patients with voice disorders, particularly with irregular vocal fold vibrations, ventricular phonation, or the phonation of individuals who have had a laryngectomy. SUMMARY: Findings from studies of normal voice physiology and of voice disorders using high-speed imaging are presented and their relevance is discussed.

Electrokymography↗

A microarray-based antibiotic screen identifies a regulatory role for supercoiling in the osmotic stress response of Escherichia coli.

Changes in DNA supercoiling are induced by a wide range of environmental stresses in Escherichia coli, but the physiological significance of these responses remains unclear. We now demonstrate that an increase in negative supercoiling is necessary for transcriptional activation of a large subset of osmotic stress-response genes. Using a microarray-based approach, we have characterized supercoiling-dependent gene transcription by expression profiling under conditions of high salt, in conjunction with the microbial antibiotics novobiocin, pefloxacin, and chloramphenicol. Algorithmic clustering and statistical measures for gauging cellular function show that this subset is enriched for genes critical in osmoprotectant transport/synthesis and rpoS-driven stationary phase adaptation. Transcription factor binding site analysis also supports regulation by the global stress sigma factor rpoS. In addition, these studies implicate 60 uncharacterized genes in the osmotic stress regulon, and offer evidence for a broader role for supercoiling in the control of stress-induced transcription.

Anti-Bacterial Agents↗

Bootstrap estimates of chaotic dynamics.

Bootstrap sampling is a nonparametric method for estimating the standard error of a statistic. This paper describes the application of bootstrap sampling to estimate the error in local linear approximations of the dynamics on chaotic attractors reconstructed from time series measurements. We present an algorithm for identifying influential points, i.e., observations with an especially large effect on a least-squares fit, and an algorithm to estimate the standard error of regression coefficients obtained from total least squares. We also consider the application of bootstrap methods to assess the uncertainty in Lyapunov exponent computations from chaotic time series.

Journal Article↗

Frequency domain dipole localization: extensions of the method and applications to auditory and visual evoked potentials.

We describe a statistical frequency domain approach to localizing equivalent dipole generators of human brain evoked potentials. The frequency domain representation allows considerable data reduction, constrains the magnitude function of the dipoles to be smooth, and accounts for the statistical properties of the background EEG. A previous paper described a restrictive model in which the dipole orientations were assumed to be fixed over time, and only one dipole was allowed. In this paper, we consider the more general model in which the orientation can vary over time, and which includes multiple dipole generators. The varying orientation model has the practical advantage of being more nearly linear and more flexible than the fixed orientation model, which facilitates convergence of the iterative fitting algorithm. We suggest a measure of goodness-of-fit that compares the likelihood of the dipole model with the likelihoods of saturated and null models. We report the results of fitting the model to recorded auditory and visual evoked potentials. A single dipole with fixed orientation seems to be an adequate model of the auditory midlatency response, while two dipoles with varying orientation are needed to fit the later P200 component. Analysis of the visual P100 response to unilateral stimulation localized a generator in the contralateral occipital cortex, as expected from anatomical considerations. A two-dipole model fit the visual P100 response of bilateral stimulations, and the locations of the two dipoles were similar to the locations obtained by single-dipole fits to the responses to left and right unilateral stimuli.

Computer Simulation↗

Comparison of pattern recognition methods for computer-assisted classification of spectra of heart sounds in patients with a porcine bioprosthetic valve implanted in the mitral position.

The diagnostic performance of two pattern recognition methods (or classifiers) to detect valvular degeneration was evaluated in 48 patients with a porcine bioprosthetic heart valve inserted in the mitral position. Twenty patients had a normal porcine bioprosthetic valve and 28 patients had a degenerated bioprosthetic valve. One method was based on the Gaussian-Bayes model and the second on the "nearest neighbor" algorithm using three distance measurements. Eighteen diagnostic features were extracted from the sound spectrum of each patient and, for each method, a two-class supervised learning approach was used to determine the most discriminant diagnostic patterns composed of 6 features or less. The probability of error of the classifiers was estimated with the leave-one-out approach. The performance of each method to discriminate between normal and degenerated bioprosthetic valves was verified by clinical evaluation of the valves. The best performance in evaluation of the sound spectrum (98% correct classifications) was obtained with the Bayes classifier and two patterns of six features each. The percentage of false positive classifications of valve degeneration was 0% and the percentage of false negative classifications was 4%. Sensitivity for the detection of valve degeneration was 96%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 95%. The best performance of the nearest neighbor method (94% correct classifications) was obtained by using the Mahalanobis distance and five patterns composed of three, four, five, or six diagnostic features. Using a pattern composed of only three features, the percentage of false positive classifications for degeneration was 10% and the percentage of false negative classifications was 4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Bayes Theorem↗

Design and analysis of a content-based pathology image retrieval system.

A prototype, content-based image retrieval system has been built employing a client/server architecture to access supercomputing power from the physician's desktop. The system retrieves images and their associated annotations from a networked microscopic pathology image database based on content similarity to user supplied query images. Similarity is evaluated based on four image feature types: color histogram, image texture, Fourier coefficients, and wavelet coefficients, using the vector dot product as a distance metric. Current retrieval accuracy varies across pathological categories depending on the number of available training samples and the effectiveness of the feature set. The distance measure of the search algorithm was validated by agglomerative cluster analysis in light of the medical domain knowledge. Results show a correlation between pathological significance and the image document distance value generated by the computer algorithm. This correlation agrees with observed visual similarity. This validation method has an advantage over traditional statistical evaluation methods when sample size is small and where domain knowledge is important. A multi-dimensional scaling analysis shows a low dimensionality nature of the embedded space for the current test set.

Abstracting and Indexing↗

Evaluating markers for selecting a patient's treatment.

Selecting the best treatment for a patient's disease may be facilitated by evaluating clinical characteristics or biomarker measurements at diagnosis. We consider how to evaluate the potential impact of such measurements on treatment selection algorithms. For example, magnetic resonance neurographic imaging is potentially useful for deciding whether a patient should be treated surgically for Carpal Tunnel Syndrome or should receive less-invasive conservative therapy. We propose a graphical display, the selection impact (SI) curve that shows the population response rate as a function of treatment selection criteria based on the marker. The curve can be useful for choosing a treatment policy that incorporates information on the patient's marker value exceeding a threshold. The SI curve can be estimated using data from a comparative randomized trial conducted in the population as long as treatment assignment in the trial is independent of the predictive marker. Estimating the SI curve is therefore part of a post hoc analysis to determine whether the marker identifies patients that are more likely to benefit from one treatment over another. Nonparametric and parametric estimates of the SI curve are proposed in this article. Asymptotic distribution theory is used to evaluate the relative efficiencies of the estimators. Simulation studies show that inference is straightforward with realistic sample sizes. We illustrate the SI curve and statistical inference for it with data motivated by an ongoing trial of surgery versus conservative therapy for Carpal Tunnel Syndrome.

Algorithms↗

Kinetics of cycle length dependence of ventricular repolarization: effect of autonomic blockade.

INTRODUCTION: Beat-to-beat adaptation of ventricular repolarization duration to cardiac cycle length and autonomic activity has not been previously characterized in the spontaneously beating human heart. METHODS AND RESULTS: The ECG of 14 healthy subjects was recorded from the supine and upright positions. Autonomic blockade was accomplished by atropine and propranolol. RR and RT intervals were measured by a computer algorithm, and the impulse response (h) from RR to RT computed. In the supine position the maximal adjustment of the RT interval occurred in the first beat following a change in cycle length (hpeak = 17.8 +/- 1.6 msec/sec), but continued to be detectable for 3.8 seconds (2.9-4.7 sec). Propranolol attenuated the peak impulse response to 15.8 +/- 4.0 msec/sec (P = NS). In the standing position the peak impulse response was increased to 25.2 +/- 5.0 msec/sec (P = 0.004 vs supine), and the impulse response duration (hdur) shortened to 1.4 seconds (1.3-1.6). This was reversed by beta blockade (hpeak = 10.7 +/- 3.6 [P = 0.005 vs standing]; hdur = 5.5 sec [4.8-6.1]). Parasympathetic and combined autonomic blockade resulted in too little residual heart rate variability to estimate the impulse response accurately. The slope of the regression of delta RT and delta RR in the supine position was 0.0177 +/- 0.0016, which was closely correlated with the peak impulse response (r = 0.91). CONCLUSIONS: System identification techniques can assist in characterizing the cycle dependence of ventricular repolarization and may provide new insights into conditions associated with abnormal repolarization.

Adult↗

Inter- and intra-variability of pigmented skin lesions: could the ABCD rule be influenced by host characteristics?

BACKGROUND/PURPOSE: Many differences in color, shape and dimension exist between different moles even in the same individual. Major differences might be accounted for anatomical location, genetic factors and by environmental factors, mainly sunlight exposure. Therefore, it would be of great value, when evaluating skin lesions, to take into account the degree of intra- and inter-variability of several diagnostic parameters. In order to assess the morphologic and chromatic differences between lesions belonging to different patients and between lesions belonging to the same individual, we examined objective digital parameters obtained with dermatoscopic analysis, using the DBDermo MIPS system (BIO MIPS Engineering, S.R.L, siena, Italy). METHODS: The automatic classifier inside the software is based on a 'match by similarity' algorithm, based on the measurement of the Euclidean distances of all variables considered from the reference image. Two-hundred and four clinically benign pigmented lesion, belonging to 18 patients were examined, stored and automatically processed. For each lesion objective parameters related to geometry, color and texture were automatically evaluated. RESULTS: We found skin color (healthy skin) is objectively different from subject to subject and the lesion color is more similar among different lesions of the same patient than among lesions belonging to different individuals both in their darkest and slightly dark component. We also observed that lesion dimensions are individual correlates, i.e. the probability for a lesion to be large is higher when the other, in the same patient, is large. CONCLUSION: Many parameters of pigmented skin lesions evaluated by digital dermoscopy analysis are similar in the same patient and different from those belonging to different individuals. This indicates that, when considering a lesion, we should take into account the peculiar patient's characteristics.

Diagnosis, Computer-Assisted↗

Pain tolerance in patients presenting to primary care and physiotherapy services with upper limb disorders.

BACKGROUND: Arm pain is a common cause of incapacity for work and is often attributed to occupational activities, but in many cases the pathogenesis is unclear. OBJECTIVE: To investigate whether arm pain in the absence of identifiable underlying pathology is associated with reduced tolerance of painful sensory stimuli. METHODS: 133 incident cases of arm pain, recruited from primary care and physiotherapy services, were classified according to a validated diagnostic algorithm. Pain tolerance was measured at three sites in each arm in response to electrocutaneous stimulation. Associations with pain tolerance (the geometric mean of the six measurements at 5 Hz) were assessed by linear regression, and findings were summarised as proportional changes in pain tolerance. RESULTS: Pain tolerance was generally lower than in an earlier community survey. Women had a lower tolerance than men. After allowance for sex, age, use of analgesics and anatomical extent of pain, there was no indication of reduced tolerance in patients with non-specific pain relative to those with specific local pathology. CONCLUSIONS: Pain tolerance may be generally reduced in patients presenting to medical services with arm pain, but those with non-specific pain do not seem to have lower tolerance than those with identifiable local pathology.

Adult↗

Instrumentation of digital gray-scale US.

Modern, high-resolution, gray-scale, ultrasound (US) imaging equipment is computer based, with all hardware signal processing functions under software control. This systems architecture permits maximum flexibility in function, rapid upgrades, and reliable performance. With modern US equipment, the spatial dimensions of the analog image are transformed into a digital matrix of picture elements (pixels). The volume of tissue, or voxel, that contributes to the echo amplitudes received from each pixel depends crucially on the section (ie, "slice") thickness at the voxel depth. Partial volume effects are more likely to occur in a longer voxel located at a depth outside the section thickness focal zone. The echo signal voltage, or amplitude, is acquired by an analog-to-digital converter simultaneously with the pixel location of the image echo origin. The most accurate echo amplitudes (with least partial volume averaging) occur at the highest image magnification when the voxel dimensions are the smallest in and out of the scan plane. With computer-based imaging, postprocessing procedures, such as fill-in algorithms and digital calipers (measurements of distances in images), can be used to aid in diagnosis.

Analog-Digital Conversion↗

[Effect of anti-hypertensive therapy with irbesartan on the absolute cardiovascular risk].

Blockade of the renin-angiotensin system with angiotensin converting enzyme inhibitors or with angiotensin receptor antagonists confers patients with arterial hypertension (AH) and associated risk factors, target organ lesion or cardiovascular disease with greater protection in morbidity and mortality terms. The objective of the present study was to evaluate the effect of irbesartan, an angiotensin II receptor antagonist, on the absolute cardiovascular risk in a cohort of hypertensive patients with moderate, high, or very high cardiovascular risk. This was a multicenter, prospective, observational, cohort study with 1974 patients (63 11 years; 47% males) with newly diagnosed essential AH or AH non-controlled with anti-hypertensive monotherapy, and moderate to very high cardiovascular risk. Irbesartan therapy at a dosage of 150300 mg was instituted as monotherapy or associated with hydrochlorothiazide, 12.5 mg. The clinical follow-up was 6 months. The evaluated parameters included the absolute cardiovascular risk, measured either quantitatively (Framingham algorithm) or qualitatively (low, moderate, high, and very high risk groups following the WHO/International Hypertension Society guidelines). Irbesartan therapy led to a significant (p = 0.0001) decrease in SBP (from 170.9 18.4 to 138.5 16.5 mmHg) and DBP (from 96.6 11 to 82 9 mmHg). The quantitative absolute cardiovascular risk decreased by 29.8% (from 12.14 8 to 8.65 6.2; p < 0.0001). The percentage of patients with very high cardiovascular risk decreased from 1.52% to 0.51% and that for patients with high cardiovascular risk from 92.77% to 88.32%. The latter patients changed to the moderate risk group. As a result, this moderate risk group increased from 5.71% to 11.17%. The adverse reaction rate was very low as only 2.2% of patients had some adverse reaction. In conclusion, irbesartan as monotherapy or associated with hydrochlorothiazide has been shown to be effective in reducing the absolute cardiovascular risk, which is obtained by a substantial decrease in arterial pressure and a good safety profile on the biochemical parameters. Tolerability was excellent, with a very low rate of adverse reactions.

Angiotensin Receptor Antagonists↗