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Acuity profile perimetry: description of technique and preliminary clinical trials.

Acuity profile perimetry is a technique that allows visual acuity properties to be rapidly measured at any location in the visual field. This report describes our initial clinical trials with acuity profile perimetry, as performed in combination with standard static perimetry. Preliminary results from patients with cataracts, amblyopia, and central serous retinopathy show, in general, a much greater deficit for acuity profiles than for static sensitivity profiles. In contrast, patients with optic neuritis or other optic neuropathies display approximately equivalent losses for static and acuity profiles. The recovery process in optic neuritis is also about equal for the two functions. Our initial findings suggest that acuity profile perimetry may be a valuable differential diagnostic test, particularly for cases in which optic nerve disease is suspected.

Adult↗

A clinical profile of otitis media without an intact tympanic membrane.

An otitis media with effusion algorithm developed by Paradise et al has become the basis for many studies of otitis media. However, it has been shown to be too ambitious (low specificity) and too optimistic (absence of fluid does not necessarily mean normal ears). We developed a four-point profile to characterize the condition of the middle ear, but it cannot be used when the eardrum is perforated (with a functioning tube or chronic perforation). We propose a three-point profile for use without an intact tympanic membrane, and we report the validation of the profile by findings at myringotomy and by the preoperative profile. This postoperative profile and the previously described profile for ears with an intact tympanic membrane should increase the accuracy of middle ear assessment in following the course of otitis media over time.

Acoustic Impedance Tests↗

Effect of antenatal steroid administration on the fetal biophysical profile.

PURPOSE: Our objective was to determine whether antenatal steroid administration affects the biophysical profile score in fetuses. METHODS: A prospective study was conducted in 84 fetuses between 28 and 34 weeks' menstrual age at risk of preterm delivery. Two intramuscular injections of 12 mg of betamethasone were given to the mother 24 hours apart. All fetuses underwent biophysical profile testing prior to and between 24 and 48 hours after steroid administration. Biophysical profiles (including nonstress tests) were evaluated by two maternal-fetal medicine specialists blinded to the timing of steroid administration. Neonatal outcome, including Apgar score, menstrual age at delivery, admission to and length of stay in the neonatal intensive care unit, and mortality, was analyzed in all subjects. RESULTS: In 31 (37%; 95 confidence interval, 26.6-47.2%) of 84 cases, the biophysical profile score decreased at least 2 points after steroid administration. The most commonly affected variables were fetal breathing and the nonstress test. There was no significant difference in the neonatal outcome between the fetuses whose biophysical profile decreased and those whose did not. CONCLUSIONS: Biophysical profile scores were decreased in more than one third of fetuses within 48 hours of antenatal steroid administration, but neonatal outcome was not affected. Knowledge of this occurrence could avoid incorrect decision making regarding fetal well-being.

Adult↗

Multivariate reconstruction of lymphocyte profiles in a two-dimensional graphical model as a tool for the investigation of lymphocyte subset distribution in health and disease.

Advanced multivariate data-analytical techniques are proposed to concisely represent and evaluate complex lymphocyte profiles (i.e., compound lymphocyte subset distributions) of individual subjects in easily interpretable, two-dimensional, graphical correlation biplots. The lymphocyte profile of each subject is represented by its location in the model, and the score of a subject for a particular lymphocyte subset is inferred from the perpendicular projection on a rotated axis that coincides with this lymphocyte subset. Simultaneously, the model yields information about the correlation between the lymphocyte subsets. Furthermore, individuals with aberrant lymphocyte profiles can be easily identified. In case studies of 80 healthy donors and of 40 patients with multiple myeloma, 10 patients with monoclonal gammopathy of undetermined significance, and 50 age- and sex-matched healthy donors, reconstruction of the two-dimensional lymphocyte profiles from 27 flow-cytometric characterized lymphocyte subsets succeeded in representing 43% and 51% of the total information (variability) contained within the 80 x 27 (= 2,160) and 100 x 27 (= 2,700) flow cytometry measurements, respectively. It is concluded from the present studies that the correlation biplot represents a unique and powerful tool to concisely describe, represent, and analyze complex lymphocyte profiles of individual subjects and the heterogeneity in lymphocyte profiles among these subjects.

Adult↗

Fourier analysis of facial profiles of young twins.

Twins studies provide a powerful approach to determining the relative contribution of genetics and environment to observed variation. Such studies assume trait differences in monozygous (MZ) twins are due to environmental factors and those in dizygous (DZ) twins are due to both genetic and environmental factors. This study quantitated facial profiles of twins using Fourier equations, determining their value in profile analysis and the assessment of the genetic contribution to facial shape. Standardized profile slide photographs of 79 pairs of 4-6 year-old twins (37 MZ pairs, 42 DZ pairs) were scanned and x and y coordinates were extracted from each profile using sellion and Camper's plane as references. The coordinates were subjected to Fourier analysis and the normalised vertex projection coefficients were studied. The means of the differences between coefficients for MZ co-twins did not differ significantly from that of DZ co-twins, although the DZ group showed higher mean differences in the higher harmonics. Subjective examination of superimposed reconstructions showed wider variation between DZ co-twins than MZ co-twins. Correct classification of twins by discriminant function analysis using Fourier coefficients was similar for both groups (MZ: 70.3%; DZ: 73.8%). Fourier analysis could quantitate facial profiles of young children and differentiate some details, but was unable to discriminate between genetic and environmental influences, and any possible interactions between these influences, on their overall facial profiles at this developmental stage.

Child↗

The utility of Wechsler Adult Intelligence Scale profile analysis with prisoners.

Determined the efficacy of profile analysis with a prison population (63 white, 63 black) of the Petersburg Federal Correctional Institution as Ss. By use of Veldman's Hierarchical Profile Analysis, five distinctive WAIS profile types were derived empirically for each racial group. Analyses of covariance that controlled for full-scale IQ differences revealed significant differences among the profile types within each race in terms of Stanford Achievement Test scores and MMPI T-scores. Further, partial correlations indepepdent of full-scale IQ revealed significant relationships between some of the profile types and the commission of rule infractions while incarcerated. These findings are interpreted as supportive of profile analysis with inmate populations. However, it is suggested that further research be effected to cross-validate these findings.

Adolescent↗

A comparison of MMPI profile types across standard and contemporary norms.

Changes in mean elevation, dispersion, overall configuration, and code type of well-defined MMPI profiles derived from diagnostic groups with known clinical correlates were examined after transformation using contemporary norms developed by Colligan, Osborne, Swenson, and Offord (1983). A total of 34 MMPI profiles from both Gilberstadt and Duker (1965) and Marks, Seeman, and Haller (1974) were analyzed using contemporary normalized T scores. Results yielded the expected reduction in mean elevation and dispersion about the mean upon transformation to contemporary norms. Linear and contemporary normalized T-score profiles correlated highly with each other and manifested a similar pattern of correlation with Skinner and Jackson's (1978) three modal MMPI types. Similarity in the code types of 94% of the profiles was found. However, the substantial number of order changes in the scales that comprise the code type evident upon transformation highlights the caution and care necessary when one is interpreting MMPI profiles based on contemporary norms. Continued use of original norms together with contemporary norms appears indicated until the full implications of profile and code type differences upon transformation to contemporary norms are understood.

Humans↗

Capillary electrokinetic separation techniques for profiling of drugs and related products.

Capillary electrokinetic separation techniques offer high efficiency and peak capacity, and can be very useful for the analysis of samples containing a large variety of (unknown) compounds. Such samples are frequently met in impurity profiling of drugs (detection of potential impurities in a pharmaceutical substance or product) and in general sample profiling (determination of differences or similarities between samples). In this paper, the potential, merits, and limitations of electrokinetic separation techniques for profiling purposes are evaluated using examples from literature. A distinction is made between impurity profiling, forensic profiling and profiling of natural products, and the application of capillary zone electrophoresis, micellar electrokinetic chromatography, and capillary electrochromatography in these fields is discussed. Attention is devoted to important aspects such as selectivity, resolution enhancement, applicability, detection, and compound confirmation and quantification. The specific properties of the various electrokinetic techniques are discussed and compared with more conventional techniques as liquid chromatography.

Cations↗

Rapid recognition of aberrant dHPLC elution profiles using the Transgenomic Navigator software.

Despite the availability of numerous technologies for detecting mutations, only a few have been formatted for automated mutation calling. Here, we evaluate the utility of the Transgenomic Navigator software to facilitate automated detection of aberrant denaturing high performance liquid chromatography (dHPLC) elution profiles. We used dHPLC to identify germline variants in MSH6, NEIL2, NEIL3, and OGG1 in 172 patients with multiple colorectal adenomas. 3,747 dHPLC profiles were analysed with the Navigator software using three levels of analysis, each differing in the degree of operator input. 43.5% (60/138) and 98.3% (59/60) of products with profiles distinct from wild type ('outliers') harboured novel variants under Level 1 and Levels 2/3 analysis conditions, respectively. We also assessed the utility of the software to rapidly detect samples carrying common polymorphisms by analysing regions of the genes that harbour polymorphisms with minor allele frequencies between 8 and 40%, therein analysing 2,784 profiles. We showed that 1573/1612 (97.6%) and 1137/1172 (97.0%) of PCR products were correctly classified as wild-type and variant, respectively (Level 3 analysis conditions). Finally, we assessed the utility of the software to detect novel variants in fragments that also harboured common polymorphisms and showed that 59/61 (96.7%) of products with profiles outlying both the wild type and polymorphism groups harboured novel variants. We conclude that the Navigator software provides an excellent tool for rapid discrimination of aberrant dHPLC elution profiles that harbour sequence variants.

Chromatography, High Pressure Liquid↗

Profiling the humoral immune response in colon cancer patients: diagnostic antigens from Streptococcus bovis.

The human bowel contains a large and dynamic bacterial population that is not only essential for intestinal health, but also critical for the development of diseases such as cancer. In this respect, the Gram-positive bacterium Streptococcus bovis has been associated with colon cancer for many years. To investigate the clinical importance of this association, an immunocapture mass spectrometry assay was developed that can generate infection-related protein profiles. The composition of these profiles is governed by the capture of specific antigens by serum antibodies from colon cancer patients. This assay showed that S. bovis antigen profiles could distinguish 11 out of 12 colon cancer patients from 8 control subjects, whereas antigen profiles derived from the gut bacterium Escherichia coli were not diagnostic for colon cancer. Moreover, S. bovis antigen profiles were also detected in polyp patients, indicating that infection with this bacterium does occur early during carcinogenesis. Highly accurate tandem mass spectrometry was used to identify one of the diagnostic antigens as a surface-exposed heparin-binding protein, which might be involved in attachment of S. bovis to tumor cells. Together, these findings corroborate the hypothesis that colonic lesions provide a specific niche for S. bovis, resulting in tumor-associated "silent" infections. These infections, however, only become apparent in colon cancer patients with a compromised immune system (bacteremia) or coincidental cardiac valve lesions (endocarditis). This makes profiling of the humoral immune response against "silent" S. bovis infections a promising diagnostic tool for the early detection of human colon cancer, which is crucial for the effective treatment of this disease.

Antibody Formation↗

Cell responses to BMP-2 and IGF-I released with different time-dependent profiles.

During wound healing, growth factors are expressed in time-dependent amounts. Constant delivery of biomolecules, however, is often used to influence cell and tissue behavior. In the present studies, a crosslinked gelatin-coating system was used to deliver bone morphogenetic protein 2 (BMP-2) or insulin-like growth factor (IGF-I) to three types of mesenchymal cells with three temporally varying release profiles. The "early" delivery profile released most of the growth factor within the first 2 days. The "pseudo-zero-order" profile approximated constant rate of delivery for about 5 days. The "late" delivery profile released most of the growth factor after about 5 days. Early delivery of IGF-I had the greatest effect on mitogenesis of SaOS-2 human osteosarcoma cells with a secondary effect noted nearly 5 days after delivery was completed. Late delivery of BMP-2 resulted in greatest alkaline phosphatase (AP) activity in mouse pluripotent C3H10T1/2 cells. Rat bone marrow stromal cells (BMCs) responded to all delivery profiles of BMP-2, with the duration of elevated AP activity increasing as the amount of BMP-2 delivered increased. In addition to an early increase in AP activity, late release also stimulated BMCs over a longer portion of the culture period. BMCs responded similarly to SaOS-2 cells when seeded on early IGF-I delivery coatings, increasing AP activity after delivery had ended. Overall, these studies further show the importance of delivery profile, specifically the characteristics of time and concentration, on cell and tissue responses.

Animals↗

Osteoblasts and osteocytes respond differently to oscillatory and unidirectional fluid flow profiles.

Bone cells subjected to mechanical loading by fluid shear stress undergo significant architectural and biochemical changes. The models of shear stress used to analyze the effects of loading bone cells in vitro include both oscillatory and unidirectional fluid shear profiles. Although the fluid flow profile experienced by cells within bone is most likely oscillatory in nature, to date there have been few direct comparisons of how bone cells respond to these two fluid flow profiles. In this study we evaluated morphologic and biochemical responses to a time course of unidirectional and oscillatory fluid flow in two commonly used bone cell lines, MC3T3-E1 osteoblasts and MLO-Y4 osteocytes. We determined that stress fibers formed and aligned within osteoblasts after 1 h of unidirectional fluid flow, but this response was not observed until greater than 5 h of oscillatory fluid flow. Despite the delay in stress fiber formation, oscillatory and unidirectional fluid flow profiles elicited similar temporal effects on the induction of both cyclooxygenase-2 (Cox-2) and osteopontin protein expression in osteoblasts. Interestingly, MLO-Y4 osteocytes formed organized stress fibers after exposure to 24 h of unidirectional shear stress, while the number of dendritic processes per cell increased along with Cox-2 protein levels after 24 h of oscillatory shear stress. Despite these differences, both flow profiles significantly altered osteopontin levels in MLO-Y4 osteocytes. Together these results demonstrate that the profile of fluid shear can induce significantly different responses from osteoblasts and osteocytes.

3T3 Cells↗

Morphometric evaluation of populations of neuronal profiles (cell bodies, dendrites, and nerve terminals) in the central nervous system.

Morphometric techniques have been developed to quantitatively characterize groups of transmitter-identified neuronal profiles, such as cell groups, dendrite and nerve terminal fields. These morphometric techniques will be illustrated by introducing some general tools for image analysis which can be considered as a background for the present specific applications. The following methods have been included: (1) methods to identify and quantitatively characterize, from both numerical and geometrical standpoints, groups of profiles in a two- and three-dimensional frame; (2) methods to evaluate the evenness of a certain distribution of profiles in the plane; (3) methods to identify subgroups of profiles based on their different spatial or optical density; and (4) methods to compare the distributions of two or more groups of profiles. The applications of these general tools to some neuroanatomical problems, such as cell group definition and description, have been illustrated. Practical examples performed on immunocytochemical preparations of neuronal profile populations are also given. Finally, the potentiality of numerical classification to classify and compare morphometric data has been shown. As an example, numerical classification methods have been applied to the morphometric and microdensitometric analysis of adrenaline/neuropeptide Y costoring neuronal systems of the brainstem in adult and aged rats.

Animals↗

Evaluation of SDS-polyacrylamide gel systems for the study of outer membrane protein profiles of clinical strains of Acinetobacter baumannii.

The outer membrane protein (OMP) profiles of 23 blood isolates of Acinetobacter baumannii representing all the different antimicrobial susceptibility patterns observed during a 3-year period in a Spanish hospital were studied. OMPs extracted from envelopes of sonicated cells after solubilisation with 2% of N-lauryl-sarcosinate were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) using the Laemmli's buffers. Eight running gel systems differing in the concentration of polyacrylamide (8%, 10% and 12%) and in the absence or presence of urea (4 M and 6 M) were used in a preliminary study analysing the OMP profiles of four clonally unrelated strains of A. baumannii. When this study was completed, the OMPs of the 23 A. baumannii were analysed in 10% SDS-polyacrylamide gels with 6 M urea and in 12% SDS-polyacrylamide gels. Ten OMP profiles were observed in 10% SDS-polyacrylamide gels with 6 M urea, whereas only 5 OMP profiles were visualised using 12% SDS-polyacrylamide gels. The OMP profiles obtained in 10% SDS-polyacrylamide gels with 6 M urea only partially correlated with those observed in 12% SDS-polyacrylamide gels. In conclusion, the use of 10% SDS-polyacrylamide gels with 6 M urea is recommended for the study of OMP profiles of A. baumannii.

Acinetobacter Infections↗

Comparison of laser beam intensity profiles produced by photodynamic therapy (PDT) and transpupillary thermotherapy (TTT) lasers.

BACKGROUND AND OBJECTIVES: For photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) lasers, long irradiation time (typically 1 minute or longer) is used and a large area of retina is treated. Consequently, the power stability but also the light distribution within the laser beam plays a major role. This study aimed to evaluate beam intensity profiles produced by several PDT and TTT lasers. STUDY DESIGN/MATERIALS AND METHODS: A beam profile analyzer (Cohu 4812 camera connected to a LPA-300PC, Spiricon, Logan, UT) was used to compare the beam profiles of PDT lasers: OPAL (Lumenis, USA); ACTIVIS (Quantel Medical, France), VISULAS (Zeiss, Germany). Spots of 2, 3, 4, and 5 mm were tested with each laser. Similarly, TTT lasers: OCULIGHT SLx (Iridex, CA) and IRIDIS trade mark (Quantel Medical, France) were evaluated with 2 and 3 mm spot diameter and power ranging from 200 to 1,000 mW. RESULTS: PDT lasers: OPAL had a "top hat" and homogeneous profile whatever the spot size. Numerous micro-spikes and micro-nadirs of power were observed with the ACTIVIS and the VISULAS. TTT lasers: for the IRIDIS the beam shape was rather gaussian, but the homogeneity was reduced by micro-spikes of power. With the OCULIGHT Slx the beam shape was rather top hat and only few micro-spikes or micro-nadirs of power could be disclosed. DISCUSSION: The literature tends to prove that the shape and homogeneity of the beam profile could play a role on the efficacy of the treatment. CONCLUSION: Since PDT and TTT lasers display different beam profiles, this parameter should be carefully evaluated when performing clinical evaluations of PDT or TTT treatments.

Laser Coagulation↗

Phospholipid profile of the human brain: 31P NMR spectroscopic study.

Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, and ethanolamine plasmalogen represent the six most abundant phospholipids of brain cell membrane. The ratio of the phospholipid contents (phospholipid profile) of the brain is remarkably consistent under various metabolic conditions and alteration of the phospholipid profile is believed to reflect changes in the membrane system. We describe here a simple but sensitive method to analyze the phospholipid profile of the human brain utilizing the acidified chloroform-methanol lipid extraction method of Folch et al. and 31P nuclear magnetic resonance (NMR) spectroscopy. Unique regional phospholipid profiles were consistently obtained. Although the large chemical-shift anisotropy of the 31P confined to rigid structures such as the cell membrane precludes direct observation of phospholipid profiles in living tissue, a reflection of the membrane phospholipid profiles can nevertheless be obtained by studying "NMR visible" water soluble intermediate metabolites of membrane phospholipids in vivo.

Adult↗

Efficient design of pulses with trapezoidal magnitude and linear phase response profiles.

A variation of the Shinnar-Le Roux (SLR) method of pulse envelope design that allows for control of the phase of the frequency response profile has been developed. The method makes use of the fact that a knowledge of one of the SLR polynomials in combination with a root inversion pattern for the other polynomial is sufficient to fully define the second polynomial. Optimization of the first polynomial, when cast in this form, remains nonlinear. However, it was demonstrated that the relationship between the SLR polynomials and the frequency response profile may be used to generate an initial guess for the SLR polynomials that is sufficiently accurate to allow for the application of linear optimization techniques in most cases. In practice several pulse envelopes having different root inversion patterns are investigated for each target profile. The resulting collection of pulses allows the user to trade off pulse power for profile accuracy. The proposed technique was used to design a large number of amplitude modulated excitation pulses having trapezoidal magnitude and linear phase frequency response profiles. A few examples of the resulting pulses and their response profiles are presented.

Magnetic Resonance Imaging↗

Improving the sensitivity of the sequence profile method.

The sequence profile method (Gribskov M, McLachlan AD, Eisenberg D, 1987, Proc Natl Acad Sci USA 84:4355-4358) is a powerful tool to detect distant relationships between amino acid sequences. A profile is a table of position-specific scores and gap penalties, providing a generalized description of a protein motif, which can be used for sequence alignments and database searches instead of an individual sequence. A sequence profile is derived from a multiple sequence alignment. We have found 2 ways to improve the sensitivity of sequence profiles: (1) Sequence weights: Usage of individual weights for each sequence avoids bias toward closely related sequences. These weights are automatically assigned based on the distance of the sequences using a published procedure (Sibbald PR, Argos P, 1990, J Mol Biol 216:813-818). (2) Amino acid substitution table: In addition to the alignment, the construction of a profile also needs an amino acid substitution table. We have found that in some cases a new table, the BLOSUM45 table (Henikoff S, Henikoff JG, 1992, Proc Natl Acad Sci USA 89:10915-10919), is more sensitive than the original Dayhoff table or the modified Dayhoff table used in the current implementation. Profiles derived by the improved method are more sensitive and selective in a number of cases where previous methods have failed to completely separate true members from false positives.

Amino Acid Sequence↗