Search PubMed⌕ Search

Biomedical subjects

T Duke

Publications and source records attributed to T Duke.

At least 37 records · Page 2Linked to original sources

Separation techniques.

The past two years have seen continued development of capillary electrophoresis methods. The separation performance of flowable sieving media now equals, and in some respects exceeds, that provided by gels. The application of microfabrication techniques to separation science is gaining pace. There is a continuing trend towards miniaturization and integration of separation with preparative or analytical steps. Innovative separation methods based on microfabrication technology include electrophoresis in purpose-designed molecular sieves, dielectric, trapping using microelectrodes, and force-free motion in Brownian ratchets.

Biocompatible Materials↗

Sequencing in nanofabricated arrays: a feasibility study.

The feasibility of using nanofabricated arrays as electrophoretic chambers for DNA sequencing is investigated. A specific array design, consisting of rows of closely spaced posts, separated by longer open spaces, is proposed. Molecules driven through the array by an electric field get hooked over obstacles at successive rows and their progress through the device is delayed as a consequences. The dependence of the delay time on molecular size is derived. Numerical evaluation indicates that a device of modest dimensions, operating at high fields, can rapidly resolve oligonucleotides containing several hundred bases.

DNA↗

Early markers of major adverse events in children after cardiac operations.

OBJECTIVES: The purpose of this study was to determine the physiologic variables that predict major adverse events in children in the intensive care unit after cardiac operations. METHODS: A cohort observational study was conducted. At the time of admission to the intensive care unit and 4, 8, 12, and 24 hours later the following variables were recorded: mean arterial pressure, heart rate, cardiac index, oxygen delivery, mixed venous oxygen saturation, base deficit, blood lactate, gastric intramucosal pH, carbon dioxide difference (the difference between arterial carbon dioxide tension and gastric intraluminal carbon dioxide tension), and toe-core temperature gradient. Major adverse events were prospectively identified as cardiac arrest, need for emergency chest opening, development of multiple organ failure, and death. RESULTS: Ninety children were included in the study; 12 had major adverse events and there were 4 deaths. Blood lactate level, mean arterial pressure, and duration of cardiopulmonary bypass were the only significant, independent predictors of major adverse events when measured at the time of admission to the intensive care unit. The odds ratio (95% confidence intervals) for major adverse events if a lactate level was greater than 4.5 mmol/L was 5.1 (1.2 to 21.1), for admission hypotension 2.3 (0.5 to 9.8), and for a cardiopulmonary bypass time greater than 150 minutes 13.7 (3.3 to 57.2). Four hours after admission lactate and carbon dioxide difference, and 8 hours after admission lactate and base deficit, were independently significant predictors. The odds ratios for major adverse events if the blood lactate level was greater than 4 mmol/L at 4 and 8 hours were 8.3 (1.8 to 38.4) and 9.3 (1.9 to 44.3), respectively. At no time in the first 24 hours were cardiac output, oxygen delivery, mixed venous oxygen saturation, toe-core temperature gradient, or heart rate significant predictors of major adverse events. CONCLUSIONS: In the context of our current treatment strategies, the duration of cardiopulmonary bypass and blood lactate level, measured in the early postoperative period, were the best predictors of impending major adverse events.

Blood Pressure↗

Activation of the L-arginine nitric oxide pathway in severe sepsis.

AIMS: To determine in children with sepsis syndrome and septic shock the time course of nitric oxide metabolites: nitrate and nitrite (nitrogen oxides). To determine whether serum concentrations of nitrogen oxides distinguished those children who died from sepsis from those who survived; those who required prolonged inotropic support compared with those who did not; and whether there was any relationship of the levels of nitrogen oxides to markers of tissue perfusion. METHODS: Nitrogen oxides were measured in 30 children with sepsis syndrome or septic shock at admission, 12, 24, and 48 hours. A non-septic control group had serum nitrogen oxides measured at admission. Markers of haemodynamics and tissue perfusion measured were mean arterial pressure, blood lactate, base deficit, gastric intramucosal pH, and deltaCO2 (DCO2: the difference between arterial and gastric intraluminal carbon dioxide tensions). Inotrope doses, number of organ systems failing at 48 hours, and outcome as survival were recorded. RESULTS: Children with sepsis had increased nitrogen oxide concentrations at presentation compared with a group of non-septic controls. Children with organ failure at 48 hours had higher serum nitrogen oxide concentrations than those with sepsis uncomplicated by organ failure at 48 hours. There was no difference in nitrogen oxide when patients were subgrouped according to the receipt of inotropes at 48 hours, and no association with markers of tissue perfusion, or survival. CONCLUSIONS: While this study shows that nitric oxide production is increased in sepsis in children, there was a limited relationship with clinically important markers of illness severity and no relationship to survival.

Adolescent↗

Altered activation of the L-arginine nitric oxide pathway during and after cardiopulmonary bypass.

The serum concentrations of nitrogen oxides, the stable metabolites of nitric oxide, were measured in 61 children during and after cardiopulmonary bypass (CPB) for surgery of congenital heart disease. Overall, there was a small reduction in serum nitrogen oxide concentrations during CPB, from a median of 27.5 (interquartile range 16.6-55.7) to 26.4 (15.3-40.6) mumol/l, followed by an increase in the following 24 h to 33.1 (21.3-46.7) mumol/l. The largest postoperative increases in nitrogen oxides occurred in children who developed renal impairment, or were treated with nitrovasodilators. There was no relationship between changes in serum nitrogen oxides intraoperatively and early changes in pulmonary vascular resistance, and a weak positive relationship between changes in serum nitrogen oxides and early postoperative changes in cardiac index (r2 = 0.09, p = 0.04). We found no evidence for increased activation of the L-arginine nitric oxide pathway during CPB; and the reduction in nitric oxide metabolites that occurred during CPB were of doubtful significance to pulmonary or systemic haemodynamic changes in the postoperative period.

Arginine↗

The DCO2 measured by gastric tonometry predicts survival in children receiving extracorporeal life support. Comparison with other hemodynamic and biochemical information. Royal Children's Hospital ECMO Nursing Team.

STUDY OBJECTIVE: To assess the role of gastric tonometry in monitoring children receiving extracorporeal life support (ECLS) and to determine if DCO2 or pHi in the weaning phase of ECLS predicts survival. DESIGN: A prospective study of consecutive patients treated with ECLS. SETTING: A tertiary pediatric ICU that is the ECLS referral center for Australia. PATIENTS: Twenty consecutive children receiving ECLS for cardiovascular or respiratory failure. INTERVENTIONS: All children were monitored throughout their ECLS course using a tonometer inserted into the stomach via the orogastric route. The PCO2 in the tonometer balloon was measured every 4 to 6 h and the pHi was calculated using the Henderson-Hasselbalch equation. The DCO2, which is the difference between PCO2 in tonometer saline solution and arterial blood, was calculated. We compared the ability of pHi, DCO2, heart rate, mean arterial pressure, arterial pH, base deficit, and blood lactate to predict death or survival during the weaning phase. Measurements were taken on the lowest level of support, which for veno-arterial extracorporeal membrane oxygenation and ventricular assist device was defined as the lowest ECLS pump flows, and on veno-venous extracorporeal membrane oxygenation was defined as the time of lowest ECLS gas flow. Predictive power was assessed using the receivor operating characteristic (ROC) analysis on the data collected at these times. RESULTS: In the weaning phase of ECLS, the pHi was significantly lower in children who died (pHi = 7.21; 95% confidence intervals, 7.14 to 7.28) than in those who survived (pHi = 7.38; 95% confidence intervals, 7.28 to 7.47). The DCO2 was significantly higher in children who died (23.6 mm Hg; 95% confidence intervals, 14.3 to 33.1) compared with survivors (4.7 mm Hg; 95% confidence intervals, -0.78 to 10.1). The area under the ROC curve was 0.95 for DCO2 (and 0.88 for pHi). pHi and DCO2 predicted survival better than base deficit (area under ROC curve, 0.82), blood lactate level (0.29), arterial pH (0.65), heart rate (0.62), and mean arterial pressure (0.74). CONCLUSIONS: DCO2 is a clinically meaningful measurement in children receiving ECLS. A high DCO2 was a good predictor of death in this series. Gastric tonometry may provide a useful measure of the adequacy of regional perfusion and oxygenation in this group of patients.

Acidosis↗

Cardiopulmonary effects of propofol infusion in llamas.

OBJECTIVE: To evaluate selected cardiopulmonary responses to propofol 2 infusion rates in nonpretreated llamas breathing room air. ANIMALS: 5 adult llamas (3 males, 2 females) with mean +/- SD body weight of 135 +/- 17.7 kg. PROCEDURE: After anesthesia induction with propofol (2 mg/kg of body weight, IV), llamas received either propofol infusion 0.2 mg/kg/min (group 1) or 0.4 mg/kg/min (group 2) for 60 minutes. Measurements, taken before anesthesia induction and at regular intervals during infusion were: direct blood pressures, heart and respiratory rates, cardiac output, and arterial blood gas tensions. Systemic and pulmonary vascular resistance, cardiac and stroke indices, and plasma bicarbonate and base excess concentrations were calculated. RESULTS: At 3 to 60 minutes after either dosage of propofol, PaCO2 and heart rate increased in all llamas; at the same time, PaO2 and arterial pH decreased. Mean pulmonary artery and central venous pressures, and stroke index decreased at 3 to 60 minutes after either dosage of propofol. Mean arterial pressure decreased at 30 to 60 minutes after infusion of 0.4 mg of propofol/kg/min; pulmonary arterial wedge pressure decreased at 20 to 40 minutes and 3 to 60 minutes after infusion of 0.2 and 0.4 mg of propofol/kg/min, respectively. Mean time from termination of infusion to sternal recumbency was 7 (group 1) and 13 (group 2) minutes. Standing was achieved in a mean 11 (group 1) and 22 (group 2) minutes. CONCLUSION: Propofol infusion rate of 0.2 mg/kg/min was considered too low to maintain a suitable depth of anesthesia, but 0.4 mg/kg/min was considered sufficient for noninvasive procedures with minimal cardiopulmonary depression.

Anesthetics, Intravenous↗

Motor protein mechanics: a stochastic model with minimal mechanochemical coupling.

A stochastic model for the action of motor proteins such as kinesin is presented. The mechanical components of the enzyme are 1) two identical head domains that bind to discrete sites on a microtubule and that are capable of undergoing a conformational change; and 2) an elastic element that connects each head to the rest of the molecule. We investigate the situation in which the strain dependence of the chemical reaction rates is minimal and the heads have independent biochemical cycles. The enzyme advances stochastically along a filament when one head detaches and diffuses to a new binding site, while the other head remains bound to the microtubule. We also investigate the case in which the chemical cycles of the heads are correlated so that the molecule shifts each head alternately. The predictions of the model are found to be in agreement with experimentally measured force-velocity relationships for kinesin-both when the force is applied externally and when the enzyme is loaded by a viscous drag. For reasonable values of the parameters, this agreement is quantitative. The molecular stepping characteristics observed in recent motility assays are also reproduced. A number of experiments are suggested that would provide a more stringent test of the model and help determine whether this simple picture is an appropriate description of motor proteins or whether models that include strain-dependent reaction rates or more complicated types of cooperation of the two heads need to be considered.

Animals↗

Intraabdominal carbon dioxide insufflation in the pregnant ewe. Uterine blood flow, intraamniotic pressure, and cardiopulmonary effects.

BACKGROUND: Laparoscopic surgical procedures are being performed in pregnant women with increasing frequency. Maternal-fetal physiologic changes occurring during intraabdominal carbon dioxide insufflation are poorly understood, and maternal-fetal safety is of concern during carbon dioxide pneumoperitoneum. A previous pilot study using end-tidal carbon dioxide-guided ventilation resulted in maternal and fetal acidosis and tachycardia during carbon dioxide pneumoperitoneum. Using serial arterial PCO2 to guide ventilation, this study was designed to evaluate maternal-fetal cardiopulmonary status, uterine blood flow, and the intraamniotic pressure effects of intraabdominal carbon dioxide insufflation in singleton pregnant ewes between 120 and 135 days of gestation. METHODS: In a prospective randomized cross-over study, nine ewes were to receive either abdominal insufflation with carbon dioxide to an intraabdominal pressure of 15 mmHg (n = 9; insufflation group) or receive no insufflation (n = 9; control group). Anesthesia was induced with thiopental and maintained with end-tidal halothane (1 to 1.5 minimum alveolar concentration/100% oxygen). Mechanical ventilation was guided by serial maternal arterial blood gas analysis to maintain PaCO2 between 35 and 40 mmHg. Data from insufflated animals were collected during insufflation (60 min) and after desufflation (30 min). Control group data were collected and matched to similar time intervals for 90 min. Ewes were allowed to recover, and after a rest period (48 h) they were entered in the cross-over study. RESULTS: During insufflation there was a significant increase (P < 0.05) in maternal PaCO2 to end-tidal carbon dioxide gradient and minute ventilation, with concomitant decreases in maternal end-tidal carbon dioxide and PaO2. Intraamniotic pressure increased significantly during insufflation. No significant changes were observed in maternal hemodynamic variables, fetal variables, or in uterine blood flow during the study. There were no fetal deaths or preterm labor in any of the animals during the experiment. CONCLUSIONS: During the 1-h insufflation, a marked increase in PaCO2-to-end-tidal carbon dioxide gradient was observed, suggesting that capnography may be an inadequate guide to ventilation during carbon dioxide pneumoperitoneum in the pregnant patient. No other significant circulatory changes were observed.

Amnion↗

Trapping of branched DNA in microfabricated structures.

We have observed electrostatic trapping of tribranched DNA molecules undergoing electrophoresis in a microfabricated pseudo-two-dimensional array of posts. Trapping occurs in a unique transport regimen in which the electrophoretic mobility is extremely sensitive to polymer topology. The arrest of branched polymers is explained by considering their center-of-mass motion; in certain conformations, owing to the constraints imposed by the obstacles a molecule cannot advance without the center of mass first moving a short distance backwards. The depth of the resulting local potential well can be much greater than the thermal energy so that escape of an immobilized molecule can be extremely slow. We summarize the expected behavior of the mobility as a function of field strength and topology and point out that the microfabricated arrays are highly suitable for detecting an extremely small number of branched molecules in a very large population of linear molecules.

Bacteriophage lambda↗