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Opening versus closing wedge osteotomy of the curved ulna in radial clubhand.

The use of an opening or closing wedge osteotomy to straighten the curved ulna in radial clubhands was simulated by using a specially designed computer program. Sixty-eight lateral x-ray films of curved ulnas in 39 children aged from a few weeks to early adolescence were examined. When lengthening is possible, closing wedge osteotomies yield, at best, only millimeters gain in length. Many will decrease bone length. There is no advantage in using multiple closing wedges. Opening wedges of reasonable angle will lengthen the ulna by 5 mms or more. Some multiple opening wedges can produce slightly better gains in length, but no more than two wedges should be used.

Adolescent↗

Relying solely on historical surgical times to estimate accurately future surgical times is unlikely to reduce the average length of time cases finish late.

STUDY OBJECTIVE: To determine whether using only previous cases' surgical times for predicting accurately surgical times of future cases is likely to reduce the average length of time cases finish late (after their scheduled finish times). DESIGN: Computer simulation. MEASUREMENTS AND MAIN RESULTS: Data from an operating room (OR) information system for two surgical suites were analyzed. For each case performed in fiscal year 1996, we searched backward for 1 year and counted the number of previous cases that were the same type of procedure performed by the same surgeon. Then, for each suite, surgical times were fitted to a statistical model estimating the effect of the type of procedure and who the surgeon was on surgical time. The estimated "variance components" were used in Monte-Carlo computer simulations to evaluate whether a hypothetical increase in the number of previous cases available to estimate the next case's surgical time would improve scheduling accuracy. Predictions of how long newly scheduled cases should take were impaired because 36.5% +/- 0.4% (mean +/- SE) of cases at a tertiary surgical suite and 28.6% +/- 0.7% of cases at an ambulatory surgery center did not have any cases in the previous year with the same procedure type and surgeon. Computer simulation was used to generate additional hypothetical cases. Using this data, even having many previous cases on which to base predictions of future surgical times would only decrease the average length of time that cases finish late by a few minutes. CONCLUSION: An OR manager considering using only historical surgical times to estimate future surgical times should first investigate, using data from their own surgical suite, what percentage of cases do not have historical data. Even if there are sufficient historical data to estimate future surgical times accurately, relying solely on historical times is probably an ineffective strategy to have future cases finish on time.

Ambulatory Surgical Procedures↗

Parthenolide and its photochemically synthesized 1(10)Z isomer: chemical reactivity and structure-activity relationship studies in human leucocyte chemotaxis.

The present study has achieved the photochemical conversion of a germacrolide into a melampolide. The investigation on their chemical properties allowed us to evaluate the minimum interatomic distance needed for transannular bridging of C(10) ring in germacrolides and to explain the regiochemical selectivity of electrophilic cyclizations. The antiinflammatory activity of parthenolide and its semisynthetic derivatives was evaluated by in vitro chemotaxis assay with human neutrophiles. These structure-activity relationship studies have led to hypothesize a new pharmacophore and have provided useful information for computationally designed drugs.

Anti-Inflammatory Agents, Non-Steroidal↗

Imaging findings of some buccomasseteric masses.

OBJECTIVE: The purpose of this study was to review and illustrate the appearances on diagnostic images of pathologic conditions of the buccomasseteric region. STUDY DESIGN: Computed tomographic, sonographic, and magnetic resonance images of the buccomasseteric masses were reviewed retrospectively. RESULTS: In our series of 66 cases, there were 60 benign lesions; of these, 21 were benign masses, 11 were inflammations, and 28 were myopathies. The most common pathologic condition of the buccomasseteric region was masseteric hypertrophy (n = 22). The most common lesion manifesting as a benign mass in this series was hemangioma (n = 10), which was followed by lipoma (n = 6). Six of the 66 patients had malignant tumors. CONCLUSIONS: Computed tomography and magnetic resonance imaging were useful in demonstrating the location and extent of the buccomasseteric masses. Sonography provided clear images of internal architectures of the mass in this region.

Adolescent↗

Clinical monitoring of ocular physiology using digital image analysis.

AIM: To examine the use of image analysis to quantify changes in ocular physiology. METHOD: A purpose designed computer program was written to objectively quantify bulbar hyperaemia, tarsal redness, corneal staining and tarsal staining. Thresholding, colour extraction and edge detection paradigms were investigated. The repeatability (stability) of each technique to changes in image luminance was assessed. A clinical pictorial grading scale was analysed to examine the repeatability and validity of the chosen image analysis technique. RESULTS: Edge detection using a 3 x 3 kernel was found to be the most stable to changes in image luminance (2.6% over a +60 to -90% luminance range) and correlated well with the CCLRU scale images of bulbar hyperaemia (r=0.96), corneal staining (r=0.85) and the staining of palpebral roughness (r=0.96). Extraction of the red colour plane demonstrated the best correlation-sensitivity combination for palpebral hyperaemia (r=0.96). Repeatability variability was <0.5%. CONCLUSIONS: Digital imaging, in conjunction with computerised image analysis, allows objective, clinically valid and repeatable quantification of ocular features. It offers the possibility of improved diagnosis and monitoring of changes in ocular physiology in clinical practice.

Journal Article↗

Binding studies using ion-selective electrodes. Examination of the picrate-albumin interaction as a model system.

We are studying the binding of ligands to macromolecules by using ligand ion selective electrodes as transducers. The picrate-bovine albumin interaction is examined in detail as a model system. A picrate ion selective electrode is used to monitor the free picrate concentration directly in the presence of albumin and bound ligand. The binding parameters are estimated and the effect of protein concentration, ionic strength, pH, and temperature is studied. The experimental data are interpreted with a specially designed computer program that performs nonlinear least-squares fitting of the generalized Scatchard model with an infinite number of classes of binding sites directly to the raw potentiometric data. The binding parameters (binding constant and maximum number of ligands that can be bound), the nonspecific binding as well as their standard deviations are estimated by this program. The principles described can be used for the potentiometric study of any ligand-binder interaction.

Electrodes↗

Novel selective inhibitors of the interaction of individual nuclear hormone receptors with a mutually shared steroid receptor coactivator 2.

Nuclear hormone receptor (NR) signaling, currently a therapeutic target in multiple diseases, involves an ordered series of protein interactions to regulate transcription in response to changing hormone levels. Later steps in the process of ligand-dependent signaling are driven by a highly conserved interaction between the NRs and the steroid receptor coactivators (SRCs) that is effected by a conserved interaction motif (L1XXL2L3), known as an NR box. Using computational design and combinatorial chemistry, we have produced novel alpha-helical proteomimetics of the second NR box of SRC2 that exploit structural differences between human estrogen receptor alpha (hERalpha), human estrogen receptor beta (hERbeta), and human thyroid hormone receptor beta (hTRbeta). The resulting library sequentially replaced each leucine with non-natural side chains. Screening this library using a quantitative competition assay revealed compounds that selectively inhibit the interaction of SRC2-2 with each individual NR in preference to its interaction with the other NR. This approach generated highly selective compounds from one that had no specificity for a particular family member. These compounds represent the first family-member-selective competitive inhibitors of the protein interactions of transcription factors.

Biomimetic Materials↗

A "sea urchin" family of boranes and carboranes: the 6m + 2n electron rule.

A new family of related borane and carborane cages has been designed computationally. These compounds obey a new electron counting rule (6m + 2n rule) rather than Wade's rule. The structures of these cages can be conceived by combining m aromatic pyramidal and n aromatic triangular units. The interstitial electrons from the m pyramids (six electrons for each unit) and the n triangles (two electrons for each unit) constitute the total 6m + 2n skeletal electrons. The greater number of skeletal electron pairs in large closo-borane cages (e.g., B32H328- or C8B24H32) achieves stabilization through the optimal occupancy of all bonding orbitals. The favorable electronic structure, the large HOMO-LUMO gaps, the large lowest positive frequencies, and the local aromaticity of the pyramidal and triangular units (as demonstrated by the large negative NICS values) of the new large closo-cages auger well for their eventual experimental realization.

Journal Article↗

N-phenylphenylglycines as novel corticotropin releasing factor receptor antagonists.

Screening of a computationally designed synthetic library led to the discovery of the N-phenylphenylglycines (NPPGs) as a novel class of human corticotropin releasing factor (h-CRF(1)) antagonists. Several NPPGs with greater potency than the original hit 1 were rapidly identified, and resolution of the racemate demonstrated that only the R-enantiomer displays activity. This structural class represents the first example of a non-peptide CRF(1) antagonist with a stereochemically distinct receptor binding affinity.

Animals↗

Redistribution of glutamate and glutamine in slices of human neocortex exposed to combined hypoxia and glucose deprivation in vitro.

This study was undertaken to elucidate the roles of neurons and glial cells in the handling of glutamate and glutamine, a glutamate precursor, during cerebral ischemia. Slices (400-600 microns) from human neocortex obtained during surgery for epilepsy or brain tumors were incubated in artificial cerebrospinal fluid and subjected to 30 min of combined hypoxia and glucose deprivation (an in vitro model of brain ischemia). These slices, and control slices that had not been subjected to "ischemic" conditions, were then fixed and embedded. Ultrathin sections were processed according to a postembedding immunocytochemical method with polyclonal antibodies raised against glutamate or glutamine, followed by colloidal gold-labeled secondary antibodies. The gold particle densities over various tissue profiles were calculated from electron micrographs using a specially designed computer program. Combined hypoxia and glucose deprivation caused a reduced glutamate immunolabeling in neuronal somata, while that of glial processes increased. Following 1 h of recovery, the glutamate labeling of neuronal somata declined further to very low values, compared to control slices. The glutamate labeling of glial cells returned to normal levels following recovery. In axon terminals, no consistent change in the level of glutamate immunolabeling was observed. Immunolabeling of glutamine was low in both nerve terminals and neuronal somata in normal slices and was reduced to nondetectable levels in nerve terminals upon hypoxia and glucose deprivation. This treatment was also associated with a reduced glutamine immunolabeling in glial cells. Reversed glutamate uptake due to perturbations of the transmembrane ion concentrations and membrane potential probably contributes to the loss of neuronal glutamate under "ischemic" conditions. The increased glutamate labeling of glial cells under the same conditions can best be explained by assuming that glial cells resist a reversal of glutamate uptake, and that their ability to convert glutamate into glutamine is compromised due to the energy failure. The persistence of a nerve terminal pool of glutamate is compatible with recent biochemical data indicating that the exocytotic glutamate release is contingent on an adequate energy supply and therefore impeded during ischemia.

Brain Ischemia↗

A method to achieve control of dietary macronutrient composition in ad libitum diets consumed by free-living subjects.

OBJECTIVE: To validate a shop system in controlling macronutrient composition during ad libitum dietary intervention. DESIGN: Six months randomized intervention trial. SETTING: A shop at the department from which all foods were collected free of charge and registered by a purpose-designed computer system. SUBJECTS: Sixty-five free-living obese subjects (25 kg/m2 < BMI < 34 kg/m2) recruited through advertisement and from a waiting list at the Department. Total drop-out rate was 8%. INTERVENTIONS: Ad libitum low-fat diets (30 energy-% (E%) fat): (1) High-protein (25 E% protein, HP) or (2) Low-protein, (12 E% protein, LP) or habitual diet (controls, C). MAIN OUTCOME MEASURES: Compliance was assessed by 24 h urinary nitrogen excretion (24 h UN). RESULTS: After one month of dietary intervention 24 h UN increased significantly in the HP group and decreased significantly in the LP group (Group difference 95% CI):6.8 g (5.0-8.7 g), P < 0.0001). This group difference remained throughout the trial. There was good agreement between protein intake as estimated by the shop computer and as estimated from 24 h UN in both first (r = 0.86) and second half of the intervention (r = 0.80). CONCLUSION: The high dietary compliance demonstrates the potential of this method to control macronutrient composition in ad libitum dietary intervention studies in free-living subjects.

Adolescent↗

Development and use of fluorescent nanosensors for metabolite imaging in living cells.

To understand metabolic networks, fluxes and regulation, it is crucial to be able to determine the cellular and subcellular levels of metabolites. Methods such as PET and NMR imaging have provided us with the possibility of studying metabolic processes in living organisms. However, at present these technologies do not permit measuring at the subcellular level. The cameleon, a fluorescence resonance energy transfer (FRET)-based nanosensor uses the ability of the calcium-bound form of calmodulin to interact with calmodulin binding polypeptides to turn the corresponding dramatic conformational change into a change in resonance energy transfer between two fluorescent proteins attached to the fusion protein. The cameleon and its derivatives were successfully used to follow calcium changes in real time not only in isolated cells, but also in living organisms. To provide a set of tools for real-time measurements of metabolite levels with subcellular resolution, protein-based nanosensors for various metabolites were developed. The metabolite nanosensors consist of two variants of the green fluorescent protein fused to bacterial periplasmic binding proteins. Different from the cameleon, a conformational change in the binding protein is directly detected as a change in FRET efficiency. The prototypes are able to detect various carbohydrates such as ribose, glucose and maltose as purified proteins in vitro. The nanosensors can be expressed in yeast and in mammalian cell cultures and were used to determine carbohydrate homeostasis in living cells with subcellular resolution. One future goal is to expand the set of sensors to cover a wider spectrum of metabolites by using the natural spectrum of bacterial periplasmic binding proteins and by computational design of the binding pockets of the prototype sensors.

Cells↗

Cost-effectiveness and patient satisfaction with pregnancy day care for hypertensive disorders of pregnancy.

OBJECTIVE: To quantify the cost-effectiveness of, and evaluate patient satisfaction with, day care for management of hypertensive disorders of pregnancy. DESIGN: Retrospective descriptive study. SETTING: Pregnancy Day Care Centre, Royal Women's Hospital, Melbourne. SAMPLE: A total of 1200 consecutive women attending with a hypertensive disorder of pregnancy. METHODS: Sociodemographic details and perinatal outcome were entered in a purpose designed computer program. A satisfaction questionnaire was administered to 130 women. Clinical costing data were calculated by casemix analysts to compare traditional inpatient and day care models of care. RESULTS: An admission to the Pregnancy Day Care Centre cost an average of 684.85 dollars less than a traditional inpatient admission. Women had an overwhelming preference for day care. CONCLUSION: Pregnancy day care is a cost-effective method of providing care for women with hypertensive disorders of pregnancy. Women prefer day care to inpatient care.

Adult↗

Surgical skills training: simulation and multimedia combined.

CONTEXT: Basic surgical skills are needed throughout the medical profession, but current training is haphazard and unpredictable. There is increasing pressure to provide transparency about training and performance standards. There is a clear need for inexperienced learners to build a framework of basic skills before carrying out surgical procedures on patients. Effective learning of a skill requires sustained deliberate practice within a cognitive framework, and simulation offers an opportunity for safe preparation. OBJECTIVES: This paper presents a new approach to basic surgical skills training, where tuition using a specially designed computer program is combined with structured practice using simulated tissue models. This approach to teaching has evolved from practical experience with surgical skills training in workshops. METHODS: Pilot studies with 72 first-year medical students highlighted the need for separate programs for teaching and for self-directed learning. The authors developed a training approach in the light of this experience. Subsequent in-depth observational and interview studies examined (a) individual teaching sessions between surgical teachers and learners (five consultant surgeons and five senior house officers) and (b) group teaching sessions with general practitioners (14 participants in three group interviews). Further work has resulted in a self-directed learning program. CONCLUSIONS: Qualitative analysis of observational and interview data provides strong preliminary support for the effectiveness of this approach. The response of teachers and learners was extremely positive. The combination of information (presented by computer) and practice of psychomotor skill (using simulated tissue models) could be extended to other surgical and practical skills.

Clinical Competence↗

Solution multistability in first-order nonlinear differential delay equations.

The dependence of solution behavior to perturbations of the initial function (IF) in a class of nonlinear differential delay equations (DDEs) is investigated. The structure of basins of attraction of multistable limit cycles is investigated. These basins can possess complex structure at all scales measurable numerically although this is not necessarily the case. Sensitive dependence of the asymptotic solution to perturbations in the initial function is also observed experimentally using a task specific electronic analog computer designed to investigate the dynamics of an integrable first-order DDE.

Journal Article↗

Obstetric ultrasonographic findings and fetal chromosomal abnormalities: refining the association.

OBJECTIVE: In an attempt to refine the role of ultrasonography in screening and identifying fetuses at risk for chromosomal abnormalities, a retrospective review of patients undergoing genetic amniocentesis was undertaken. STUDY DESIGN: Computer databases from the perinatal biology laboratory and cytogenetics laboratory of our institution were correlated to compare the results of the fetus' ultrasonographic examination with the cytogenetic results from amniocentesis. Univariate and multivariate analysis were used to determine the best correlations between ultrasonographic findings and chromosomal abnormalities (study 1). The results were used to construct regression analysis formulas and a Neural Network program to predict the presence or absence of chromosomal abnormalities in a second set of patients (study 2) undergoing genetic amniocentesis. RESULTS: One hundred twenty-five chromosomal abnormalities were found in 3775 fetuses in study 1 (3.3%). Multivariate analysis showed significant correlations between anomalies of the central nervous system, heart, face and neck, and extremities and increased nuchal fold, increased bowel echogenicity, abnormal biparietal diameter-to-femur ratio, and the presence of chromosomal abnormalities. Regression equations and a Neural Network program successfully predicted the presence or absence of fetal chromosomal abnormalities in a second set of 901 at-risk fetuses. CONCLUSION: A normal ultrasonographic examination result in patients who are at increased risk for fetal chromosomal abnormalities reduces the risk 2- to 3-fold, whereas the presence of any major ultrasonographic abnormality or certain minor abnormalities significantly increases the risk. The application of these results to low-risk patients is still premature.

Adolescent↗