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Biomedical subjects

J A White

Publications and source records attributed to J A White.

At least 19 recordsLinked to original sources

Density functional theory of fluids in nanopores: analysis of the fundamental measures theory in extreme dimensional-crossover situations.

Two density functional theories, the fundamental measures theory of Rosenfeld [Phys. Rev. Lett. 63, 980 (1989)] and a subsequent approximation by Tarazona [Phys. Rev. Lett. 84, 694 (2000)] are applied to the study of the hard-sphere fluid in two situations: the cylindrical pore and the spherical cavity. The results are compared with those obtained with grand canonical ensemble Monte Carlo simulations. The differences between both theories are evaluated and interpreted in the terms of the dimensional crossover from three to one and zero dimensions.

Algorithms↗

Finite-size effects in the microscopic structure of a hard-sphere fluid in a narrow cylindrical pore.

We examine the microscopic structure of a hard-sphere fluid confined to a small cylindrical pore by means of Monte Carlo simulation. In order to analyze finite-size effects, the simulations are carried out in the framework of different statistical mechanics ensembles. We find that the size effects are specially relevant in the canonical ensemble where noticeable differences are found with the results in the grand canonical ensemble (GCE) and the isothermal isobaric ensemble (IIE) which, in most situations, remain very close to the infinite system results. A customary series expansion in terms of fluctuations of either the number of particles (GCE) or the inverse volume (IIE) allows us to connect with the results of the canonical ensemble.

Journal Article↗

Plasma membrane voltage changes during nanosecond pulsed electric field exposure.

The change in the membrane potential of Jurkat cells in response to nanosecond pulsed electric fields was studied for pulses with a duration of 60 ns and maximum field strengths of approximately 100 kV/cm (100 V/cell diameter). Membranes of Jurkat cells were stained with a fast voltage-sensitive dye, ANNINE-6, which has a subnanosecond voltage response time. A temporal resolution of 5 ns was achieved by the excitation of this dye with a tunable laser pulse. The laser pulse was synchronized with the applied electric field to record images at times before, during, and after exposure. When exposing the Jurkat cells to a pulse, the voltage across the membrane at the anodic pole of the cell reached values of 1.6 V after 15 ns, almost twice the voltage level generally required for electroporation. Voltages across the membrane on the side facing the cathode reached values of only 0.6 V in the same time period, indicating a strong asymmetry in conduction mechanisms in the membranes of the two opposite cell hemispheres. This small voltage drop of 0.6-1.6 V across the plasma membrane demonstrates that nearly the entire imposed electric field of 10 V/mum penetrates into the interior of the cell and every organelle.

Cell Membrane↗

On the universal behavior of some thermodynamic properties along the whole liquid-vapor coexistence curve.

When thermodynamic properties of a pure substance are transformed to reduced form by using both critical- and triple-point values, the corresponding experimental data along the whole liquid-vapor coexistence curve can be correlated with a very simple analytical expression that interpolates between the behavior near the triple and the critical points. The leading terms of this expression contain only two parameters: the critical exponent and the slope at the triple point. For a given thermodynamic property, the critical exponent has a universal character but the slope at the triple point can vary significantly from one substance to another. However, for certain thermodynamic properties including the difference of coexisting densities, the enthalpy of vaporization, and the surface tension of the saturated liquid, one finds that the slope at the triple point also has a nearly universal value for a wide class of fluids. These thermodynamic properties thus show a corresponding apparently universal behavior along the whole coexistence curve.

Journal Article↗

Density functional theory of fluids in the isothermal-isobaric ensemble.

We present a density functional theory for inhomogeneous fluids at constant external pressure. The theory is formulated for a volume-dependent density, n(r,V), defined as the conjugate variable of a generalized external potential, nu(r,V), that conveys the information on the pressure. An exact expression for the isothermal-isobaric free-energy density functional is obtained in terms of the corresponding canonical ensemble functional. As an application we consider a hard-sphere system in a spherical pore with fluctuating radius. In general we obtain very good agreement with simulation. However, in some situations a peak develops in the center of the cavity and the agreement between theory and simulation becomes worse. This happens for systems where the number of particles is close to the magic numbers N=13, 55, and 147.

Journal Article↗

Platelet glycoprotein IIb/IIIa inhibition in acute coronary syndromes. Gradient of benefit related to the revascularization strategy.

AIMS: To assess the efficacy of platelet glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes primarily medically managed. METHODS AND RESULTS: We performed a meta-analysis of the randomized clinical trials of platelet glycoprotein IIb/IIIa inhibitor therapy in the medical management of non-ST-elevation acute coronary syndromes. Among 29570 patients, IIb/IIIa integrin blockade was associated with a reduction in death or non-fatal myocardial infarction at 30 days, from 11.5% to 10.7% (odds ratio 0.91,P =0.02). Patients undergoing percutaneous coronary intervention during index hospitalization sustained a greater reduction in ischaemic events (odds ratio 0.82, P=0.01) than patients medically managed (odds ratio 0.95, P=0.27). Among patients undergoing intervention, the benefit was more pronounced if the procedure was performed during glycoprotein IIb/IIIa inhibitor infusion (odds ratio 0.74; P=0.02), than if revascularization was performed after drug discontinuation (odds ratio 0.87,P =0.17). CONCLUSION: This analysis, including the entire large-scale trial experience of intravenous glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes primarily medically managed, demonstrates an overall significant, albeit moderate, reduction in 30-day death or myocardial infarction associated with therapy. Although not based on a prospectively defined hypothesis, the findings suggest a gradient of benefit conferred by these agents depending on the revascularization strategy used.

Acute Disease↗

Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes.

BACKGROUND: Diabetes mellitus is a major risk factor for adverse outcomes after acute coronary syndromes (ACS). Because this disease may be associated with increased platelet aggregation, we investigated whether diabetic patients with ACS derive particular benefit from platelet glycoprotein (GP) IIb/IIIa receptor inhibition. METHODS AND RESULTS: We performed a meta-analysis of the diabetic populations enrolled in the 6 large-scale platelet GP IIb/IIIa inhibitor ACS trials: PRISM, PRISM-PLUS, PARAGON A, PARAGON B, PURSUIT, and GUSTO IV. Among 6458 diabetic patients, platelet GP IIb/IIIa inhibition was associated with a significant mortality reduction at 30 days, from 6.2% to 4.6% (OR 0.74; 95% CI 0.59 to 0.92; P=0.007). Conversely, 23 072 nondiabetic patients had no survival benefit (3.0% versus 3.0%). The interaction between platelet GP IIb/IIIa inhibition and diabetic status was statistically significant (P=0.036). Among 1279 diabetic patients undergoing percutaneous coronary intervention (PCI) during index hospitalization, the use of these agents was associated with a mortality reduction at 30 days from 4.0% to 1.2% (OR 0.30; 95% CI 0.14 to 0.69; P=0.002). CONCLUSIONS: This meta-analysis, including the entire large-scale trial experience of intravenous platelet GP IIb/IIIa inhibitors for the medical management of non-ST-segment-elevation ACS, shows that these agents may significantly reduce mortality at 30 days in diabetic patients. Although not based on a randomized assessment, the survival benefit appears to be of greater magnitude in patients undergoing PCI. Therefore, the use of platelet GP IIb/IIIa inhibitors should be strongly considered in diabetic patients with ACS.

Diabetes Complications↗

Unified optimization criterion for energy converters.

We propose a unified optimization criterion for energy converters. It represents the best compromise between energy benefits and losses for a specific job and neither an explicit evaluation of entropies nor the consideration of environmental parameters are required. For all considered systems the criterion predicts a performance regime laying between those of maximum efficiency and maximum useful energy. Such regime has been invoked as optimum not only in macroscopic heat engines but also in some molecular motors.

Journal Article↗

Acquisition of texture-cued fasting-anticipatory meal-size change in rats with adequate energy intake.

To determine if an increase in intake at a meal before a long fast can be conditioned to food texture cues, male Sprague-Dawley rats were given a high- or low-fat diet in one texture (powder or pellet) for 1 h prior to a 12.5-h fast and in the other texture before a 3-h fast. Each group (N = 9) went through a pseudorandom sequence of four duplicates of each texture-fast pairing over 4 experimental days in each of three training trials, followed by one 4-day trial under extinction, i.e. without the difference in fast lengths between textures. Neither the high-fat group nor the low-fat group as a whole gave a clear indication of a learnt texture-cued increase in meal size before the longer fast relative to the shorter fast. However, the rats trained on the high-fat diet that had the highest intakes on the first 4 days of training showed a relative increase in the amount eaten of the texture predicting the longer fast during the third training trial, and this effect also approached statistical significance in the extinction test. These results provide some support for the conclusion that anticipatory hunger/satiety can be differentially conditioned to dietary texture cues, but only if sufficient food is eaten before a short fast to prevent the rise in hunger during longer fasts that reinforces the discriminative increase in meal size.

Animals↗

Assisted venous drainage cardiopulmonary bypass in congenital heart surgery.

BACKGROUND: A novel active venous drainage perfusion circuit was designed to achieve effective venous return through small venous cannulas. The efficacy and safety of this new system was investigated and compared with a conventional gravity drainage system. METHODS: Four hundred consecutive patients undergoing open heart repair of congenital heart lesions by one surgeon were studied. The first 200 patients were supported by gravity drainage and the next 200 patients were supported by assisted venous drainage. No patient in the time period was excluded from the study. RESULTS: The two groups did not differ significantly in weight, bypass time, or cross-clamp time. Priming volumes were less in the assisted group than in the gravity group (576+/-232 mL versus 693+/-221 mL, p < 0.001). Venous cannula size was smaller in the assisted group when compared with the gravity group (33.2F+/-7.4F versus 38.5F+/-7.1F, p < 0.001). There was a trend to lower operative mortality in the assisted drainage group (5 of 200, 2.5% versus 11 of 200, 5.5%; p = 0.10). Hospital stay and pulmonary, infectious, and neurologic complications were comparable in both groups. Cardiac complications were less common in the assisted group than in gravity group (22 of 200, 11% versus 38 of 200, 19%; p = 0.017). Hematologic complications were less common in the assisted group than the gravity group (6 of 200, 3% versus 19 of 200, 9.5%; p < 0.01). CONCLUSIONS: These findings suggest that assisted venous drainage is safe in congenital heart operations and facilitates the use of smaller venous cannulas.

Analysis of Variance↗

Age and valve size effect on the long-term durability of the Carpentier-Edwards aortic pericardial bioprosthesis.

BACKGROUND: Bioprosthesis durability decreases with time and younger age. However, the time-scale and determinants of durability of the aortic Carpentier-Edwards stented bovine pericardial prosthesis are incompletely characterized. METHODS: Between September 1981 and January 1984, 267 patients underwent implantation of the pericardial aortic prosthesis at four centers. Mean age at implant was 65 +/- 12 years (range 21 to 86 years). Follow-up averaged 12 +/- 4.5 years. The primary end point was explant for structural valve dysfunction (SVD), which was analyzed multivariably in the context of death as a competing risk. RESULTS: Freedom from explant due to SVD was 99%, 94%, and 77% at 5, 10, and 15 years. Risk of SVD increased exponentially with time and younger age (p = 0.0001) at implantation; an increased risk of small valve size was not reliably demonstrated (p = 0.1). Considering the competing risk of death, patients aged 65 years or older had a less than 10% chance of explant for SVD by 15 years. CONCLUSIONS: Durability of this stented pericardial aortic bioprosthesis is excellent and justifies its use in patients aged 65 or older.

Actuarial Analysis↗

Partial left ventriculectomy for dilated cardiomyopathy: is this an alternative to transplantation?

OBJECTIVE: To determine the late effectiveness of partial left ventriculectomy and risk factors for failure. METHODS: Between May 1996 and December 1998, partial left ventriculectomy and concomitant mitral valve surgery were performed in 62 patients (95% transplant candidates) with a mean age of 54 years (range 17-72 years). All patients were in New York Heart Association functional class III (38%) or IV (62%) because of idiopathic dilated cardiomyopathy (59 patients) or ischemic, valvular, or familial cardiomyopathy (1 patient each). Outcomes considered for multivariable analysis included implantation of left ventricular assist device, return to class IV heart failure, relisting for transplantation, and death. RESULTS: Partial left ventriculectomy reduced the left ventricular end-diastolic diameter immediately preoperatively to immediately postoperatively (from 8.4 +/- 1.1 cm to 5.92 +/- 0.8 cm; P =.01), reduced the left ventricular end-diastolic volume index (from 133 +/- 48.6 mL to 64.1 +/- 26 mL; P <.0001), and increased the left ventricular ejection fraction (from 16 +/- 7.6 to 31.5 +/- 10.9; P <.0001). Survival was 80% and 60% at 1 and 3 years after surgery and freedom from failure was 49% and 26%, respectively. Increased systolic pulmonary artery pressure, decreased maximum exercise oxygen consumption, and increased left atrial pressure were associated with failure and/or death. The degree of preoperative mitral regurgitation did not correlate with clinical outcome. CONCLUSIONS: Early and late failures preclude the widespread use of partial left ventriculectomy. However, in view of its sometimes beneficial effect, use in situations that do not allow for transplantation or as a biologic bridge to transplantation may be appropriate.

Adolescent↗

Systematic ab initio study of the compressibility of silicate garnets.

The structural properties of the silicate garnets andradite, Ca(3)Fe(2)Si(3)O(12), uvarovite, Ca(3)Cr(2)Si(3)O(12), knorringite, Mg(3)Cr(2)Si(3)O(12), goldmanite, Ca(3)V(2)Si(3)O(12), blythite, Mn(2+)(3)Mn(3+)(2)Si(3)O(12), skiagite, Fe(2+)(3)Fe(3+)(2)Si(3)O(12), calderite, Mn(2+)(3)Fe(3+)(2)Si(3)O(12), and khoharite, Mg(3)Fe(3+)(2)Si(3)O(12), have been investigated with a quantum-mechanical model as a function of applied pressure. The study has been performed with the density functional theory code CASTEP, which uses pseudopotentials and a plane-wave basis set. All structural parameters have been optimized. The calculated static geometries (cell parameters, internal coordinates of atoms and bond lengths), bulk moduli and their pressure derivatives are in good agreement with the experimental data available. Predictions are made for those cases where no experimental data have been reported. The data clearly indicate that the elastic properties of all silicate garnets are dominated by the compressibility of the dodecahedral site. The compression mechanism is found to be based on a bending of the angle between the centers of the SiO(4) tetrahedra and the adjacent octahedra, as in the aluminosilicate garnets. An analysis of the relationship between ionic radii of the cations and the compressibility of silicate garnets is presented.

Journal Article↗

Real-Time linux dynamic clamp: a fast and flexible way to construct virtual ion channels in living cells.

We describe a system for real-time control of biological and other experiments. This device, based around the Real-Time Linux operating system, was tested specifically in the context of dynamic clamping, a demanding real-time task in which a computational system mimics the effects of nonlinear membrane conductances in living cells. The system is fast enough to represent dozens of nonlinear conductances in real time at clock rates well above 10 kHz. Conductances can be represented in deterministic form, or more accurately as discrete collections of stochastically gating ion channels. Tests were performed using a variety of complex models of nonlinear membrane mechanisms in excitable cells, including simulations of spatially extended excitable structures, and multiple interacting cells. Only in extreme cases does the computational load interfere with high-speed "hard" real-time processing (i.e., real-time processing that never falters). Freely available on the worldwide web, this experimental control system combines good performance. immense flexibility, low cost, and reasonable ease of use. It is easily adapted to any task involving real-time control, and excels in particular for applications requiring complex control algorithms that must operate at speeds over 1 kHz.

Computer Simulation↗

Networks of interneurons with fast and slow gamma-aminobutyric acid type A (GABAA) kinetics provide substrate for mixed gamma-theta rhythm.

During active exploration, hippocampal neurons exhibit nested rhythmic activity at theta ( approximately 8 Hz) and gamma ( approximately 40 Hz) frequencies. Gamma rhythms may be generated locally by interactions within a class of interneurons mediating fast GABA(A) (GABA(A,fast)) inhibitory postsynaptic currents (IPSCs), whereas theta rhythms traditionally are thought to be imposed extrinsically. However, the hippocampus contains slow biophysical mechanisms that may contribute to the theta rhythm, either as a resonance activated by extrinsic input or as a purely local phenomenon. For example, region CA1 of the hippocampus contains a slower class of GABA(A) (GABA(A,slow)) synapses, believed to be generated by a distinct group of interneurons. Recent evidence indicates that these GABA(A,slow) interneurons project to the GABA(A, fast) interneurons that contribute to hippocampal gamma rhythms. Here, we use biophysically based simulations to explore the possible ramifications of interneuronal circuits containing separate classes of GABA(A,fast) and GABA(A,slow) interneurons. Simulated interneuronal networks with fast and slow synaptic kinetics can generate mixed theta-gamma rhythmicity under restricted conditions, including strong connections among each population, weaker connections between the two populations, and homogeneity of cellular properties and drive. Under a broader range of conditions, including heterogeneity, the networks can amplify and resynchronize phasic responses to weak phase-dispersed external drive at theta frequencies to either GABA(A,slow) or GABA(A,fast) cells. GABA(A, slow) synapses are necessary for this process of amplification and resynchronization.

Algorithms↗

Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism.

Retinoids, particularly all-trans-retinoic acid (RA), are potent regulators of cell differentiation, cell proliferation, and apoptosis. The role of all-trans-RA during development and in the maintenance of adult tissues has been well established. The control of all-trans-RA levels in cells and tissues is regulated by the balance between its biosynthesis and its catabolism to inactive metabolites. The cytochrome P450 enzyme P450RAI (herein renamed P450RAI-1) is partially responsible for this inactivation of all-trans-RA. In this report, we describe the identification, molecular cloning, and characterization of a second related enzyme, P450RAI-2, which is also involved in the specific inactivation of all-trans-RA. Transiently transfected P450RAI-2 can convert all-trans-RA to more polar metabolites including 4-oxo-, 4-OH-, and 18-OH-all-trans-RA. Competition experiments with other retinoids suggest that all-trans-RA is the preferred substrate. The high level of expression of P450RAI-2, particularly in the cerebellum and pons of human adult brain, suggests a unique role for this enzyme in the protection of specific tissues from exposure to retinoids.

Amino Acid Sequence↗

Video-assisted cardioscopy for intraventricular repair in congenital heart disease.

BACKGROUND: Video-assisted thoracoscopic surgical techniques have been widely adopted as a means to reduce surgical trauma. By adapting pediatric thoracoscopic instrumentation, we have developed a technique for video-assisted cardioscopy (VAC). We report our experience and describe the technical feasibility of VAC. METHODS: Since June 1995, 409 consecutive patients underwent 431 intracardiac procedures (ventricular septal defect, 150; tetralogy of Fallot or double outlet right ventricle, 101; atrioventricular canal, 52; subaortic stenosis, 43; valve repair, 50; Rastelli procedure, 12; Konno or Ross Konno operation, 11; and miscellaneous, 12) using VAC at Miami Children's Hospital. Using a prospective database, we tracked outcomes and operative events to delineate the usefulness and efficacy of this technique. RESULTS: VAC provided clear and precise imaging of small or remote intracardiac structures during repair of congenital heart defects without technical complications. Procedure times and aortic cross-clamp times using VAC were not prolonged. Intraoperative images were collected for every operation, documenting each patient's cardiac anatomy before and after repair. Surgery through small incisions was facilitated. Operative mortality was 1.2% (5 of 409), and no patient required reoperation before discharge. At a mean follow-up interval of 22 months, the incidence of reoperation for residual or recurrent lesions was 1.2% (5 of 404). CONCLUSIONS: Our experience demonstrates the technical feasibility and clinical utility of routine endoscopic imaging during open heart surgery for congenital heart repair.

Adolescent↗