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Biomedical subjects

B Goldstein

Publications and source records attributed to B Goldstein.

At least 19 recordsLinked to original sources
PubMed2005

Pulse and mean intracranial pressure analysis in pediatric traumatic brain injury.

OBJECTIVE: We investigated the relationship between the intracranial pulse pressure (ICPpp) and the mean intracranial pressure (ICP(M)) in pediatric patients with traumatic brain injury (TBI). METHODS: We screened ICP records of 42 patients admitted to the Pediatric Intensive Care Unit at Doernbecher Children's Hospital (OHSU) for segments in which the ICPM varied at least 5 mmHg. We found 54 ICP segments in 9 pediatric TBI patients (ages 0.2-17.8 years, mean = 9.9). ICP was continuously monitored (fs = 125 Hz). We used an automatic algorithm to detect ICP beat components. We then calculated the ICPpp and ICPM for each beat and created density plots of ICPpp vs. ICPM. RESULTS: The coefficient of linear correlation was r > 0.70 in 43/54 segments (p < 0.01). We found that an underlying linear relationship exits between ICPpp and ICPM in most 1-hour records of pediatric patients with TBI. This finding is consistent with the data in adult studies, suggesting that children with TBI demonstrate similar changes in brain compliance. However, density plots revealed that there are also nonlinear ICPpp-ICPM patterns present that are not captured by linear metrics. CONCLUSION: Although there is an underlying linear relationship between ICPpp and ICPM, nonlinear patterns are also present. Further research is required to determine if specific nonlinear ICPpp-ICPM patterns correlate with clinically significant information.

Adolescent↗
PubMed2005

A computer model of intracranial pressure dynamics during traumatic brain injury that explicitly models fluid flows and volumes.

A model of intracranial pressure (ICP) dynamics that uses fluid volumes as primary state variables is presented, along with clinical data for two subjects with elevated ICP. The data includes annotations to indicate the precise timing of clinical changes in cerebral spinal fluid drainage, head of bed elevation, and minute ventilation. The response to changes in the clinical parameters was used to calibrate the model to correspond to specific subjects by estimating values for key characteristics such as hematoma volume and CSF uptake resistance. The error in mean ICP predicted by the model was less than 2 mmHg when cerebral spinal fluid is drained and the head of bed elevation was increased. The error in mean ICP predicted by the model exceeded 5 mmHg during an episode when the head of bed was decreased and also during a reduction in minute ventilation. The estimated values for hematoma volume and other subject characteristics were plausible but could not be verified empirically.

Blood Pressure↗
PubMed2005

Combinatorial complexity and dynamical restriction of network flows in signal transduction.

The activities and interactions of proteins that govern the cellular response to a signal generate a multitude of protein phosphorylation states and heterogeneous protein complexes. Here, using a computational model that accounts for 307 molecular species implied by specified interactions of four proteins involved in signalling by the immunoreceptor FcepsilonRI, we determine the relative importance of molecular species that can be generated during signalling, chemical transitions among these species, and reaction paths that lead to activation of the protein tyrosine kinase (PTK) Syk. By all of these measures and over two- and ten-fold ranges of model parameters--rate constants and initial concentrations--only a small portion of the biochemical network is active. The spectrum of active complexes, however, can be shifted dramatically, even by a change in the concentration of a single protein, which suggests that the network can produce qualitatively different responses under different cellular conditions and in response to different inputs. Reduced models that reproduce predictions of the full model for a particular set of parameters lose their predictive capacity when parameters are varied over two-fold ranges.

Animals↗
PubMed2001

On the evolution of early development in the Nematoda.

The phylum Nematoda serves as an excellent model system for exploring how development evolves, using a comparative approach to developmental genetics. More than 100 laboratories are studying developmental mechanisms in the nematode Caenorhabditis elegans, and many of the methods that have been developed for C. elegans can be applied to other nematodes. This review summarizes what is known so far about steps in early development that have evolved in the nematodes, and proposes potential experiments that could make use of these data to further our understanding of how development evolves. The promise of such a comparative approach to developmental genetics is to fill a wide gap in our understanding of evolution--a gap spanning from mutations in developmental genes through to their phenotypic results, on which natural selection may act.

Animals↗
PubMed2001

An upstream repressor element plays a role in Igf2 imprinting.

The imprinted Igf2 gene is associated with a small upstream region that is differentially methylated on the active paternal allele. We have identified a repressor element within this sequence and shown that repression is probably mediated through a trans- acting factor, GCF2. DNA methylation of this site abrogates both protein binding and repressor activity. Targeting experiments demonstrate that this element plays a role in the repression of the maternal Igf2 gene in vivo.

Animals↗
PubMed2001

Kinetic proofreading models for cell signaling predict ways to escape kinetic proofreading.

In the context of cell signaling, kinetic proofreading was introduced to explain how cells can discriminate among ligands based on a kinetic parameter, the ligand-receptor dissociation rate constant. In the kinetic proofreading model of cell signaling, responses occur only when a bound receptor undergoes a complete series of modifications. If the ligand dissociates prematurely, the receptor returns to its basal state and signaling is frustrated. We extend the model to deal with systems where aggregation of receptors is essential to signal transduction, and present a version of the model for systems where signaling depends on an extrinsic kinase. We also investigate the kinetics of signaling molecules, "messengers," that are generated by aggregated receptors but do not remain associated with the receptor complex. We show that the extended model predicts modes of signaling that exhibit kinetic discrimination for some range of parameters but for other parameter values show little or no discrimination and thus escape kinetic proofreading. We compare model predictions with experimental data.

Animals↗
PubMed2001

Dorsal and snail homologs in leech development.

As part of an examination of how developmental mechanisms such as axis specification, cell fate specification, and segmentation have evolved, we have cloned homologs of the Drosophila melanogaster genes dorsal and snail from the glossiphoniid leech Helobdella robusta. Sequences from one dorsal-class gene (Hro-dl) and two snail-class genes (Hro-sna1 and Hro-sna2) were identified. Polyclonal antibodies were raised against the most conserved domains of HRO-DL and HRO-SNA1. Nuclear staining appeared for both proteins in mid-embryogenesis, in mesodermal and ectodermal precursors. During segmentation, segmentally iterated stripes of cells with strong HRO-DL staining appeared. The stripes of HRO-DL staining were first concentrated in the cytoplasm of cells, and later in the nuclei. Around this time, HRO-SNA levels also appeared in nuclei in segmentally iterated stripes. The localization of HRO-DL and HRO-SNA proteins raise the possibility that these genes are part of a conserved genetic pathway that, instead of specifying the dorsoventral axis and the mesoderm as in flies, might play a role in the diversification of cell types within segment primordia during leech development.

Amino Acid Sequence↗
PubMed2001

Calculations show substantial serial engagement of T cell receptors.

The serial engagement model provides an attractive and plausible explanation for how a typical antigen presenting cell, exhibiting a low density of peptides recognized by a T cell, can initiate T cell responses. If a single peptide displayed by a major histocompatibility complex (MHC) can bind, sequentially, to different T cell receptors (TCR), then a few peptides can activate many receptors. To date, arguments supporting and questioning the prevalence of serial engagement have centered on the down-regulation of TCR after contact of T cells with antigen presenting cells. Recently, the existence of serial engagement has been challenged by the demonstration that engagement of TCR can down-regulate nonengaged bystander TCR. Here we show that for binding and dissociation rates that characterize interactions between T cell receptors and peptide-MHC, substantial serial engagement occurs. The result is independent of mechanisms and measurements of receptor down-regulation. The conclusion that single peptide-MHC engage many TCR, before diffusing out of the contact region between the antigen-presenting cell and the T cell, is based on a general first passage time calculation for a particle alternating between states in which different diffusion coefficients govern its transport.

Antigen-Presenting Cells↗
PubMed2001

Computer-assisted learning in critical care: from ENIAC to HAL.

Computers are commonly used to serve many functions in today's modern intensive care unit. One of the most intriguing and perhaps most challenging applications of computers has been to attempt to improve medical education. With the introduction of the first computer, medical educators began looking for ways to incorporate their use into the modern curriculum. Prior limitations of cost and complexity of computers have consistently decreased since their introduction, making it increasingly feasible to incorporate computers into medical education. Simultaneously, the capabilities and capacities of computers have increased. Combining the computer with other modern digital technology has allowed the development of more intricate and realistic educational tools. The purpose of this article is to briefly describe the history and use of computers in medical education with special reference to critical care medicine. In addition, we will examine the role of computers in teaching and learning and discuss the types of interaction between the computer user and the computer.

Computer Simulation↗
PubMed2001

Uncoupling and recoupling of autonomic regulation of the heart beat in pediatric septic shock.

Healthy physiological systems exhibit marked signal variability and complexity, whereas diseased systems generally show a loss of variability, decreased complexity ("decomplexification"), and increased regularity. The goal of this study was to evaluate the uncoupling and recoupling phenomenon in children with septic shock by observing serial changes in heart rate variability metrics. Data were collected from 7 children with septic shock by using the computer system in the Complex Systems Laboratory at Oregon Health Sciences University. Heart rate time series were constructed and analyzed by using the Hales Research System at intervals of 6 h during pediatric intensive care unit (PICU) hospitalization. These power spectral values were then plotted vs. time. Six of seven patients showed an increase over time in low-frequency heart rate power and the low-/high-frequency ratio, whereas high-frequency heart rate power decreased. We also compared the change in mean heart rate, heart rate standard deviation, and power spectral values during the first 24 h of PICU hospitalization vs. the remainder of the PICU stay (for the 5 patients with a PICU length of stay > 48 h). Compared to the initial 24 h in the PICU, low-frequency power and the low-/high-frequency ratio increased, whereas high-frequency power decreased over the course of the illness. This report shows the potential value of monitoring the uncoupling and recoupling phenomenon in patients with septic shock. Our results are in agreement with other investigators who report evidence of decomplexification both in experimental models of sepsis and in clinical studies and provide direction for further work.

Adolescent↗
PubMed2001

Appointment scheduling system: a vehicle for increased productivity.

Operations management is the design and control of systems responsible for the productive use of human resources, equipment, and facilities in the development of a product or service. Applying those concepts to appointment scheduling can coordinate efficient use of resources. The focus of this paper is to assist the dentist and dental team in creating an appointment scheduling system that maximizes productivity and profitability.

Appointments and Schedules↗
PubMed2001

Anatomy of the peripheral nervous system.

This article is an overview of the structure and components of the peripheral nervous system. The fine structure and gross anatomy of peripheral nerves and ganglia are described. A functional and regional approach is used to highlight principles on which the peripheral nervous system is designed. Finally, the somatic and autonomic nervous systems are contrasted to underscore similarities between the two systems.

Autonomic Nervous System↗
PubMed2000

Embryonic polarity: a role for microtubules.

Researchers have suspected that initial polarization of the Caenorhabditis elegans embryo might be directed by microtubules, but demonstrating this has faced obstacles. A new study has cleverly bypassed these obstacles.

Animals↗
PubMed2000

Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group.

BACKGROUND: Endotoxin is a primary trigger of the inflammatory processes that lead to shock, multiorgan failure, and purpura fulminans in meningococcal sepsis. Bactericidal/permeability-increasing protein (BPI) is a natural protein, stored within the neutrophil granules, that binds to and neutralises the effects of endotoxin in vitro, in laboratory animals, and in humans. To establish whether a recombinant 21-kDa modified fragment of human BPI (rBPI21), containing the active antimicrobial and endotoxin-neutralising moiety, would decrease death and long-term disability from meningococcal sepsis, we did a randomised, double-blind, placebo-controlled trial of rBPI21 in children with severe meningococcal sepsis. METHODS: We enrolled children (2 weeks to 18 years of age) presenting to 22 centres in the UK and the USA with a clinical picture suggestive of meningococcal sepsis, and with evidence of severe disease. Children were randomly assigned rBPI21 (2 mg/kg over 30 min followed by 2 mg/kg over 24 h) or placebo (0.2 mg/mL human albumin solution) in addition to conventional medical therapy. Primary outcome variables were mortality, amputations, and change in paediatric overall performance category (POPC) from before illness to day 60. Analysis was by intention to treat. FINDINGS: Of 1287 patients screened, 892 were excluded, including 57 patients who died or who met criteria for imminent death before receiving the study drug. 190 patients received rBPI21, and 203 placebo. 34 (8.7%) of 393 patients died during the study: 14 (7.4%) in the rBPI21 group and 20 (9.9%) in the placebo group (odds ratio 1.31 [95% CI 0.62-2.74], p=0.48). Compared with patients randomised to placebo, fewer patients treated with rBPI21 had multiple severe amputations (six of 190 [3.2%] vs 15 of 203 [7.4%], odds ratio 2.47 [0.94-6.51], p=0.067), and more had a functional outcome similar to that before illness (as measured by the POPC scale) at day 60 (136 of 176 [77.3%] vs 126 of 190 [66.3%], p=0.019). INTERPRETATION: Because most deaths occurred in the interval between identification of patients and study drug administration, the mortality rate in the placebo group was substantially lower than predicted. The trial was therefore underpowered to detect significant differences in mortality. However, patients receiving rBPI21 had a trend towards improved outcome in all primary outcome variables. Given the excellent severity match between placebo and rBPI21 groups at study entry, the results overall indicate that rBPI21 is beneficial in decreasing complications of meningococcal disease.

Adolescent↗
PubMed2000

When cells tell their neighbors which direction to divide.

Many cells must divide in specific orientations, yet for only a handful of cases do we have some understanding of how cells choose division orientations. We know of only a few cases where division orientations are controlled by specific cell-cell interactions. These cases are of interest, because they tell us something new and seemingly fundamental about how cells can function during development. Here, the evidence that interactions control division orientation in some cells of the early C. elegans embryo is presented, and what is known about how contact can regulate division orientation is discussed. Whether contact-mediated division orientation is a peculiarity of C. elegans or whether it may be more widespread is addressed.

Animals↗
PubMed2000

Continuous propofol anaesthesia for patients with myotonic dystrophy.

Myotonic dystrophy, a rare genetic disorder, may pose a serious problem to the anaesthesiologist due to muscular and extramuscular involvement. Thirteen patients, median age 21 yr were anaesthetized by continuous propofol infusion, fentanyl, atracurium and N2O to evaluate this combination in myotonic dystrophy. Intraoperatively, neither exaggerated reactions nor haemodynamic instability was observed. Recovery was smooth and quick. Although there was a significant decrease in mean postoperative vital capacity (965 (349) ml) from the preoperative value (1664 (566) ml, P = 0.0028), there was no change in mean postoperative SpO2 and there were no perioperative respiratory complications. Only two patients complained of nausea and vomiting. Similarly, muscular hypertonia and shivering were not observed. We conclude that the combination of continuous propofol infusion and fentanyl was a successful anaesthetic technique in these young myotonic dystrophy patients undergoing peripheral surgery.

Adolescent↗
PubMed2000

Linear and nonlinear analysis of hemodynamic signals during sepsis and septic shock.

OBJECTIVE: Neuroautonomic modulation of heart rate (HR) and blood pressure were assessed in sepsis or septic shock. We hypothesized that these metrics would be diminished in pediatric patients with sepsis and septic shock, indicating uncoupling of the autonomic and cardiovascular systems. DESIGN: Prospective case series. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PATIENTS: Thirty pediatric patients with sepsis or septic shock. INTERVENTIONS: None. MEASURES AND MAIN RESULTS: Metrics used included power spectral analysis, a linear frequency domain measure, and detrended fluctuation analysis, a nonlinear technique that assesses the degree of long-range correlation in HR or blood pressure. We found decreased low-frequency (2.68 +/- 0.24 vs. 3.37 +/- 0.17 [SEM] bpm2; p = .03) and high-frequency HR power (2.18 +/- 0.14 vs. 2.79 +/- 0.23 bpm2; p = .04) and increased detrended fluctuation analysis scaling exponent (1.22 +/- 0.06 vs. 1.00 +/- 0.07 bpm2; p = .02) in sepsis vs. shock patients, respectively. Compared with sepsis or shock, recovery was associated with increases in low-frequency (3.61 +/- 0.15 vs. 3.05 +/- 0.19 bpm2; p < .0001) and high-frequency HR power (3.11 +/- 0.15 vs. 2.50 +/- 0.22 bpm2; p < .0001). CONCLUSIONS: We conclude that uncoupling of the autonomic and cardiovascular systems occurs over both short- and long-range time scales during sepsis, and the degree of uncoupling may help differentiate between sepsis, septic shock, and recovery states.

Adolescent↗