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Morphological profiles of neutron and X-irradiated small intestine.

This paper describes the response of mouse small intestine, at several time points after treatment with neutron or X-irradiation, using doses expected to give similar effects in terms of crypt/microcolony survival. Using resin histology, the effects of radiation on the numbers of duodenal cell types and measurements of tissue areas were assessed. The results for individual parameters and for an estimate of overall damage are given in a data display, which summarises the morphological profile of the organ after both types of radiation. Damage and recovery were seen for many of the parameters studied but there was no standard response pattern applicable for all parameters. In particular, the response of individual crypt cell types could not be predicted from knowledge of the change in crypt numbers. With regard to the holistic response of the gut, neutron irradiation appeared to have caused more damage and produced more early effects than the X-irradiation. More specifically, neutron treatment led to more damage to the neuromuscular components of the wall, while X-irradiation produced early vascular changes.

Animals↗

Leukocyte migration inhibition in methotrexate-induced pneumonitis. Evidence for an immunologic cell-mediated mechanism.

Methotrexate-induced pneumonitis is a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In three patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LIF), by peripheral blood lymphocytes after incubation with methotrexate (MTX) in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving methotrexate but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. Along with these results, we obtained bronchoalveolar lavage (BAL) cell data displaying high grade lymphocyte alveolitis with a lymphocyte subset inverted ratio. This production of LIF suggests that pneumonitis associated with methotrexate therapy is also associated with a specific cellular immune response to the drug.

Adolescent↗

Serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in children with insulin-dependent diabetes mellitus.

Pubertal development has recently been evaluated from the standpoint of changes in insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) levels in healthy children. We studied puberty related changes in serum IGF-I and IGFBP-3 levels in 24 patients (11 prepubertal) with insulin dependent diabetes mellitus (IDDM) and 26 healthy subjects (14 prepubertal). Serum IGF-I and IGFBP-3 levels were assayed using immunoradiometric assays and radioimmunoassays, respectively. Serum IGF-I and IGFBP-3 levels in diabetics did not increase during puberty, as opposed to those in healthy children. Serum IGF-I and IGFBP-3 levels of diabetic patients were found to be lower than those of control subjects during puberty (p < 0.0001 and p < 0.05, respectively). Proteolysis is believed to be a general mechanism to increase IGF bioavailability in the presence of IGFBPs. Increased IGFBP-3 protease activity has been shown in sera of children with IDDM as well as a decrease in this activity in response to insulin therapy. Our data displaying low IGFBP-3 levels in diabetic children may be due to increased proteolysis, which also causes a shift in IGF-I to its lower molecular weight forms. Higher rate of clearance of the latter may be the reason for the low IGF-I levels we observed in children with IDDM. The moderate correlation between insulin dose and IGFBP-3 levels (r = 0.5, p < 0.01) may suggest insulin to be a contributing factor in the regulation of IGFBP-3 levels. We conclude that regulation of IGF-I and IGFBP-3 concentrations is disturbed in children with IDDM, in particular during adolescence.

Adolescent↗

Inhaled human insulin ((insulin human [rDNA origin]) Inhalation Powder) in diabetes mellitus.

Inhaled human insulin ((insulin human [rDNA origin]) Inhalation Powder) is a prandial insulin approved in the EU and the US for the treatment of adults with diabetes. Its glycaemic control is comparable to subcutaneous insulin in Type 1 and 2 diabetes, and has superior efficacy versus oral antidiabetic agents in Type 2 diabetes. Hypoglycaemia and mild-to-moderate cough are the main side effects. The treatment group differences in pulmonary function occur early, and are small, nonprogressive for up to 2 years and reversible following discontinuation. Patient-reported outcomes data displays higher diabetes treatment satisfaction, improvements in some quality-of-life scores, and treatment preference with inhaled human insulin versus traditional means. Availability of inhaled insulin may increase insulin acceptance and thus improve glycaemic control in patients with diabetes.

Administration, Inhalation↗

Concordance between task and interface rotational and translational control improves ground vehicle performance.

Research in various areas of human-system interaction suggests the importance of examining the similarities and dissimilarities between tasks and the interfaces used to complete them. Specifically, the theory of cognitive fit suggests that human problem solvers will perform better when the data and data displays they use to complete a task match some characteristic of that task. An experiment was performed that extends the theory of cognitive fit to the realm of human performance on motor tasks. Participants completed several virtual vehicle control motor tasks that consisted of rotational and translational control components. The tasks were performed with user interfaces that either combined or separated rotational and translational control. The tasks were of two types: control of either rotation or translation changes but not both concurrently, or simultaneous control of combined rotation and translation changes. The results indicate that task performance was better when the characteristics of the interface matched the characteristics of the task. Actual or potential applications of this research include constructing ground vehicle interface controls that are designed specifically based on the characteristics of the task for which they are to be used, such as primarily driving fast and in a straight line (e.g., on a highway) versus primarily driving slowly with much turning (e.g., on a city street).

Adolescent↗

Sensitivity of a method for the analysis of facial mobility. II. Interlandmark separation.

OBJECTIVE: This study demonstrates a method of quantifying facial movements based on distortions of the skin surface. DESIGN: Landmarks were identified on the faces of five healthy human subjects (2 men and 3 women; mean age, 27.6 years; range, 26 to 29 years), and the distortions were characterized by changes in the separation between 20 pairs of landmark distances during specific maximal facial animations: smile, lip purse, cheek puff, grimace, eye closure, and eye opening. Data were recorded with a video-based tracking system for a period of 3 seconds at a sampling rate of 60 Hz or frames per second. For each subject, we analyzed the change in the separation of 20 pairs of landmarks, of which the majority were bilaterally symmetrical and functionally active. RESULTS: Characteristic patterns of movement emerged for each animation. We found that smiling involved movements of the lateral orbital, circumoral, and chin regions; grimacing involved the inner orbital, lateral orbital, lateral nasal, and upper-lip regions; eye closure involved the inner orbital, lateral orbital, and, to a lesser degree, lateral nasal regions; eye opening involved the inner and lateral orbital regions; cheek puffing involved the cheek and lower-lip regions; and the lip purse animation involved the nasolabial, cheek, commissure, and lip regions. CONCLUSION: This measurement of distortion provided a quantitative estimate of facial movement, and this approach is especially applicable to patients with unilateral problems in which the patient can serve as his or her own control.

Adult↗

Responses and pauses: discrimination and a choice catastrophe.

Pigeons produced a stimulus change either by responding or by not responding for a specified time period (by pausing). They then had to choose between two responses to obtain food. One choice was correct if the first component had been completed by a response; the other was correct if the component had been completed by a pause. The pigeons usually chose correctly, thereby indicating that they used their own prior behavior as a discriminative stimulus. Fixed pause requirements did not produce equal first component completions by a response and by a pause. To obtain equality, the pause requirement was titrated as a function of current performance. Titration resulted in equal completions and also produced accurate discrimination. In addition to showing that pigeons discriminated whether they had responded or paused, the data displayed and discontinuous functions predicted by catastrophe theory. Another procedure used forced choice rather than titration to produce equal completions by pausing and responding and also showed accurate discrimination of behavior.

Animals↗

RepGene: a spreadsheet template for the management of reporter gene assays.

One of the most powerful techniques in molecular biology is the controlled expression of specific proteins by transfection of eukaryotic cells. This method has become feasible and highly sensitive and, thus, suitable for high-throughput reporter gene assays in basic and applied research. Moreover, the limiting factors are neither the transfection efficiency nor the functional analysis, but rather the ability to manage complex experimental protocols when multiple genes are co-transfected and/or when the effects of several chemical compounds are investigated within the same experiment. Here, we describe an easy-to-use and highly flexible spreadsheet template intended to rationalize and expedite the organization and data management of multi-step reporter gene assays. The objectives of this spreadsheet template are the design of the transfection protocol, the coordination of the administration of test compounds, and the graphical presentation and statistical analysis of the results.

Data Display↗

Application of transcriptome analysis to clinical pharmacology studies.

Clinical pharmacology is the investigation of drug effects in humans. This review discusses the basic tenets of clinical pharmacology research, including pharmacokinetic and pharmacodynamic analysis, therapeutic window, and clinical trial design, and the issues that may arise in the application of transcriptome analysis to clinical pharmacology studies. Examples of how transcriptome analysis can be applied to clinical pharmacology research are described, including a model system of endotoxin challenge (in vitro and in vivo), and an example of a cross-over drug study in normal volunteers. Various data display and analysis methods are also illustrated, including principal component analysis, hierarchical cluster analysis, and pathways analysis.

Animals↗

CT of the lumbosacral spine: importance of tomographic planes parallel to vertebral end plate.

An experimental computer program capable of reformatting stored display data from a CT scanner into true cross-sectional images of the spine has been clinically tested over a 1 year period. With this program, tomographic planes exactly parallel to the vertebral end plate can be imaged at the lumbosacral level even in patients who are markedly rotated or have scoliotic deformities. The reformatted image planes are tilted in the dorsoventral and mediolateral directions to compensate for lordosis or scoliosis. The reformatting can also produce images in coronal and sagittal planes on axes other than true horizontal or vertical. The program has been used in the examination of 269 spines and has been found to be valuable in demonstrating the spinal canal and the intervertebral foramina.

Adult↗

Changes in electrical impedance of skeletal muscle measured during hyperthermia.

The electrical impedance of rat skeletal muscle was measured from 100 Hz to 40 MHz during the application of typical hyperthermia heating regimens. Trials were performed employing freshly excised tissue heated to target temperatures from 39.5 to 50 degrees C. Abrupt and rapid decreases in the low-frequency beta-dispersion occurred very shortly after reaching hyperthermia temperatures. These rapid decreases continued at a rate and to an extent dependent upon the target temperature, and then, as heating continued, abruptly changed to a much slower rate which continued indefinitely. The initial rapid changes were associated with microscopically observed muscle fibre rounding and radial shrinkage, with accompanying increasing interstitial oedema. The subsequent slow changes were associated with a slow histolysis. The time- and temperature-dependence of the rapid resistivity changes evidenced similarities to typical hyperthermia endpoint responses. An Arrhenius analysis of the rate of the resistivity changes yielded a break at 43 degrees C, with activation energies of 36.1 and 58.3 kcal/mol above and below this break. Preliminary in vivo impedance data displayed qualitative similarities to the excised tissue findings.

Animals↗

Percentage scattergram to depict changes in large amounts of data over time.

Graphical representation of changes in epidemiologic or clinical parameters over time is difficult when a large amount of data is involved. The traditional methods either cannot incorporate all necessary information (bar graphs, pie charts, tables) or are unable to depict information on more than a limited number of individuals (scattergrams). We have designed an effective way of visual presentation of the changes a variable demonstrates over time. The percentage scattergram provides accurate and complete depiction of any number of data points, allowing comprehensive and rapid analysis.

Data Display↗

Characterization of the endothelin receptors of rat myometrial plasma membranes.

Binding of 125I-endothelin-1 (human endothelin) to purified rat myometrial plasma membranes was assayed. Analysis of binding data displayed binding to two groups of receptors, a high affinity low capacity pool (Kd = 0.22 nM), and a low affinity high capacity pool (Kd = 173 nM). The high affinity pool most likely originated from contamination with vascular cell membranes, and it was concluded that the endothelin affinity to myometrial tissue is low, which is in agreement with earlier reports on the uterotonic potency.

Animals↗

UTOPIA: a consultation system for visit-by-visit diabetes management.

UTOPIA (UTilities for OPtimizing Insulin Adjustment) is a prototype computer system proposed to support home data analysis and therapy recommendations for the individual patient. The paper describes methods of analysis and their incorporation into an overall system design that matches the iterative practices at the physician-patient consultation from visit to visit. Four modules support home data display and comparison with clinical measurements; extraction of blood glucose trends and daily cycles using time series analysis, learning relationships between insulin adjustments and changes in time series patterns via a parametric, linear systems model; and advice generation by solving the linear equation for candidate insulin adjustments. Concepts and methods are placed in context, with a discussion of comparable and related research.

Algorithms↗

Visualization of inheritance patterns from graphic representation of additive and dominance relationships between animals.

Evaluation of pedigrees of normal and affected individuals help to suggest possible patterns of inheritance. Because large numbers of individuals are involved in studies of genetic disease, classic two-dimensional family tree charts are difficult to draw. Instead, DFA plots of graduated circles, weighted by dominance relationships, inbreeding, and additive relationships between individuals can be plotted above, on, and below the diagonal. Base animals without phenotypic measurements contribute information for computation of approximate dominance relationship, inbreeding, and additive relationships, but are not explicitly in the graph. Plotting only a set of randomly selected animals for each combination of phenotypes improves the visualization effect, especially when pedigrees are large or when computer resources are limited. For deficiency of uridine monophosphate synthase and interdigital hyperplasia, DFA plots showed higher densities of additive and dominance relationships among affected animals. However, DFA plots did not show clear patterns of inheritance for heel erosion, laminitis, or sole ulcers because environmental effects were important for those traits. Grouped graduated circles also improved visualization. The function of DFA plots is comparable with statistical scatter plots that display data to help examine statistical approaches. The DFA plots serve as a first approach to evaluate genetic hypotheses before a more complex model is fit.

Animals↗

Optimizing accuracy in magnetic resonance imaging-guided stereotaxis: a technique with validation based on the anterior commissure-posterior commissure line.

OBJECT: Some of the earliest successful frame-based stereotactic interventions directed toward the thalamus and basal ganglia depended on identifying the anterior commissure (AC) and posterior commissure (PC) in a sagittal ventriculogram and defining the intercommissural line that connects them in the midsagittal plane. The AC-PC line became the essential landmark for the localization of neuroanatomical targets in the basal ganglia and diencephalon and for relating them to stereotactic atlases. Stereotactic/functional neurosurgery has come to rely increasingly on magnetic resonance (MR) imaging guidance, and methods for accurately determining the AC-PC line on MR imaging are being developed. The goal of the present article is to present the authors' technique. METHODS: The technique described uses MR sequences that minimize geometric distortion and registration error, thereby maximizing accuracy in AC-PC line determinations from axially displayed MR data. The technique is based on the authors' experience with the Leksell G-frame but can be generalized to other MR imaging-based stereotactic systems. This methodology has been used in a series of 62 stereotactic procedures in 47 adults (55 pallidotomies and seven thalamotomies) with preliminary results that compare favorably with results reported when using microelectrode recordings. The measurements of the AC-PC line reported here also compare favorably with those based on ventriculography and computerized tomography scanning. CONCLUSIONS: The methodology reported here is critical in maintaining the accuracy and utility of MR imaging as its role in modern stereotaxy expands. Accurate parameters such as these aid in ensuring the safety, efficacy, and reproducibility of MR-guided stereotactic procedures.

Adult↗