Clinical Studies on Epidural and Spinal Postoperative Analgesia : With Special Reference to Continuous Techniques of Administration and Adjuvant Drugs

Continuous epidural analgesia (CEA) and continuous spinal postoperative analgesia (CSPA) provided by a mixture of local anaesthetic and opioid are widely used for postoperative pain relief. E.g., with the introduction of so-called microcatheters, CSPA found its way particularly in orthopaedic surgery. These techniques, however, may be associated with dose-dependent side-effects as hypotension, weakness in the legs, and nausea and vomiting. At times, they may fail to offer sufficient analgesia, e.g., because of a misplaced catheter. The correct position of an epidural catheter might be confirmed by the supposedly easy and reliable epidural stimulation test (EST). The aims of this thesis were to determine a) whether the efficacy, tolerability, and reliability of CEA might be improved by adding the α2-adrenergic agonists adrenaline and clonidine to CEA, and by the repeated use of EST during CEA; and, b) the feasibility of CSPA given through a microcatheter after vascular surgery. Studies I IV were double-blinded, randomized, and controlled trials; Study V was of a diagnostic, prospective nature. Patients underwent arterial bypass surgery of the legs (I, n=50; IV, n=46), total knee arthroplasty (II, n=70; III, n=72), and abdominal surgery or thoracotomy (V, n=30). Postoperative lumbar CEA consisted of regular mixtures of ropivacaine and fentanyl either without or with adrenaline (2 µg/ml (I) and 4 µg/ml (II)) and clonidine (2 µg/ml (III)). CSPA (IV) was given through a microcatheter (28G) and contained either ropivacaine (max. 2 mg/h) or a mixture of ropivacaine (max. 1 mg/h) and morphine (max. 8 µg/h). Epidural catheter tip position (V) was evaluated both by EST at the moment of catheter placement and several times during CEA, and by epidurography as reference diagnostic test. CEA and CSPA were administered for 24 or 48 h. Study parameters included pain scores assessed with a visual analogue scale, requirements of rescue pain medication, vital signs, and side-effects. Adrenaline (I and II) had no beneficial influence as regards the efficacy or tolerability of CEA. The total amounts of epidurally-infused drugs were even increased in the adrenaline group in Study II (p=0.02, RM ANOVA). Clonidine (III) augmented pain relief with lowered amounts of epidurally infused drugs (p=0.01, RM ANOVA) and reduced need for rescue oxycodone given i.m. (p=0.027, MW-U; median difference 3 mg (95% CI 0 7 mg)). Clonidine did not contribute to sedation and its influence on haemodynamics was minimal. CSPA (IV) provided satisfactory pain relief with only limited blockade of the legs (no inter-group differences). EST (V) was often related to technical problems and difficulties of interpretation, e.g., it failed to identify the four patients whose catheters were outside the spinal canal already at the time of catheter placement. As adjuvants to lumbar CEA, clonidine only slightly improved pain relief, while adrenaline did not provide any benefit. The role of EST applied at the time of epidural catheter placement or repeatedly during CEA remains open. The microcatheter CSPA technique appeared effective and reliable, but needs to be compared to routine CEA after peripheral arterial bypass surgery.

Modern computed tomography techniques in stroke management

Technological development of fast multi-sectional, helical computed tomography (CT) scanners has allowed computed tomography perfusion (CTp) and angiography (CTA) in evaluating acute ischemic stroke. This study focuses on new multidetector computed tomography techniques, namely whole-brain and first-pass CT perfusion plus CTA of carotid arteries. Whole-brain CTp data is acquired during slow infusion of contrast material to achieve constant contrast concentration in the cerebral vasculature. From these data quantitative maps are constructed of perfused cerebral blood volume (pCBV). The probability curve of cerebral infarction as a function of normalized pCBV was determined in patients with acute ischemic stroke. Normalized pCBV, expressed as a percentage of contralateral normal brain pCBV, was determined in the infarction core and in regions just inside and outside the boundary between infarcted and noninfarcted brain. Corresponding probabilities of infarction were 0.99, 0.96, and 0.11, R² was 0.73, and differences in perfusion between core and inner and outer bands were highly significant. Thus a probability of infarction curve can help predict the likelihood of infarction as a function of percentage normalized pCBV. First-pass CT perfusion is based on continuous cine imaging over a selected brain area during a bolus injection of contrast. During its first passage, contrast material compartmentalizes in the intravascular space, resulting in transient tissue enhancement. Functional maps such as cerebral blood flow (CBF), and volume (CBV), and mean transit time (MTT) are then constructed. We compared the effects of three different iodine concentrations (300, 350, or 400 mg/mL) on peak enhancement of normal brain tissue and artery and vein, stratified by region-of-interest (ROI) location, in 102 patients within 3 hours of stroke onset. A monotonic increasing peak opacification was evident at all ROI locations, suggesting that CTp evaluation of patients with acute stroke is best performed with the highest available concentration of contrast agent. In another study we investigated whether lesion volumes on CBV, CBF, and MTT maps within 3 hours of stroke onset predict final infarct volume, and whether all these parameters are needed for triage to intravenous recombinant tissue plasminogen activator (IV-rtPA). The effect of IV-rtPA on the affected brain by measuring salvaged tissue volume in patients receiving IV-rtPA and in controls was investigated also. CBV lesion volume did not necessarily represent dead tissue. MTT lesion volume alone can serve to identify the upper size limit of the abnormally perfused brain, and those with IV-rtPA salvaged more brain than did controls. Carotid CTA was compared with carotid DSA in grading of stenosis in patients with stroke symptoms. In CTA, the grade of stenosis was determined by means of axial source and maximum intensity projection (MIP) images as well as a semiautomatic vessel analysis. CTA provides an adequate, less invasive alternative to conventional DSA, although tending to underestimate clinically relevant grades of stenosis.

Continuous-Flow Surface Aeration Systems

An aeration process in ail activated sludge plant is a continuous-flow system. In this system, there is a steady input flow (flow from the primary clarifier or settling tank with some part from the secondary clarifier or secondary settling tank) and output flow connection to the secondary clarifier or settling tank. The experimental and numerical results obtained through batch systems can not be relied on and applied for the designing of a continuous aeration tank. In order to scale up laboratory results for field application, it is imperative to know the geometric parameters of a continuous system. Geometric parameters have a greater influence on the mass transfer process of surface aeration systems. The present work establishes the optimal geometric configuration of a continuous-flow surface aeration system. It is found that the maintenance of these optimal geometric parameters systems result in maximum aeration efficiency. By maintaining the obtained optimal geometric parameters, further experiments are conducted in continuous-flow surface aerators with three different sizes in order to develop design curves correlating the oxygen transfer coefficient and power number with the rotor speed. The design methodology to implement the presently developed optimal geometric parameters and correlation equations for field application is discussed.

Simultaneous material selection and geometry design of statically determinate trusses using continuous optimization

In this work, we explore simultaneous geometry design and material selection for statically determinate trusses by posing it as a continuous optimization problem. The underlying principles of our approach are structural optimization and Ashby’s procedure for material selection from a database. For simplicity and ease of initial implementation, only static loads are considered in this work with the intent of maximum stiffness, minimum weight/cost, and safety against failure. Safety of tensile and compression members in the truss is treated differently to prevent yield and buckling failures, respectively. Geometry variables such as lengths and orientations of members are taken to be the design variables in an assumed layout. Areas of cross-section of the members are determined to satisfy the failure constraints in each member. Along the lines of Ashby’s material indices, a new design index is derived for trusses. The design index helps in choosing the most suitable material for any geometry of the truss. Using the design index, both the design space and the material database are searched simultaneously using gradient-based optimization algorithms. The important feature of our approach is that the formulated optimization problem is continuous, although the material selection from a database is an inherently discrete problem. A few illustrative examples are included. It is observed that the method is capable of determining the optimal topology in addition to optimal geometry when the assumed layout contains more links than are necessary for optimality.

Rendering stiffer walls: a hybrid haptic system using continuous and discrete time feedback

Instability in conventional haptic rendering destroys the perception of rigid objects in virtual environments. Inherent limitations in the conventional haptic loop restrict the maximum stiffness that can be rendered. In this paper we present a method to render virtual walls that are much stiffer than those achieved by conventional techniques. By removing the conventional digital haptic loop and replacing it with a part-continuous and part-discrete time hybrid haptic loop, we were able to render stiffer walls. The control loop is implemented as a combinational logic circuit on an field-programmable gate array. We compared the performance of the conventional haptic loop and our hybrid haptic loop on the same haptic device, and present mathematical analysis to show the limit of stability of our device. Our hybrid method removes the computer-intensive haptic loop from the CPU-this can free a significant amount of resources that can be used for other purposes such as graphical rendering and physics modeling. It is our hope that, in the future, similar designs will lead to a haptics processing unit (HPU).

Analysis of continuous beams—a three dimensional elasticity solution

A three dimensional elasticity solution for the analysis of beams continuous over an infinite number of equally spaced supports has been given. The beam has been subjected to normal tractions on its two opposite faces and these loads are identical over each span. The other two faces are traction free. Numerical results have been given for different cases when the beam is loaded on its bottom face. The results obtained have been compared with the results of two dimensional elasticity solution.

Characterization of a continuous CO2 laser-welded Fe-Cu dissimilar couple

Continuous CO2 laser welding of an Fe-Cu dissimilar couple in a butt-weld geometry at different process conditions is studied. The process conditions are varied to identify and characterize the microstructural features that are independent of the welding mode. The study presents a characterization of the microstructure and mechanical properties of the welds. Detailed microstructural analysis of the weld/base-metal interface shows features that are different on the two sides of the weld. The iron side can grow into the weld with a local change in length scale, whereas the interface on the copper side indicates a barrier to growth. The interface is jagged, and a banded microstructure consisting of iron-rich layers could be observed next to the weld/Cu interface. The observations suggest that solidification initiates inside the melt, where iron and copper are mixed due to convective flow. The transmission electron microscopy (TEM) of the weld region also indicates the occasional presence of droplets of iron and copper. The microstructural observations are rationalized using arguments drawn from a thermodynamic analysis of the Fe-Cu system.

A novel approach for large-scale polypeptide folding based on elastic networks using continuous optimization

We present a new computationally efficient method for large-scale polypeptide folding using coarse-grained elastic networks and gradient-based continuous optimization techniques. The folding is governed by minimization of energy based on Miyazawa–Jernigan contact potentials. Using this method we are able to substantially reduce the computation time on ordinary desktop computers for simulation of polypeptide folding starting from a fully unfolded state. We compare our results with available native state structures from Protein Data Bank (PDB) for a few de-novo proteins and two natural proteins, Ubiquitin and Lysozyme. Based on our simulations we are able to draw the energy landscape for a small de-novo protein, Chignolin. We also use two well known protein structure prediction software, MODELLER and GROMACS to compare our results. In the end, we show how a modification of normal elastic network model can lead to higher accuracy and lower time required for simulation.

Low Power continuous time common mode sensing for common mode feedback circuits

Continuous common mode feedback (CMFB) circuits having high input impedance and low distortion are proposed. The proposed circuits are characterized for 0.18 mu m CMOS process with 1.8 V supply. Simulation results indicate that the proposed common mode detector consumes no standby power and CMFB circuit consumes 27-34% less power than previous high swing CMFB circuits.

Protein sequence design on the basis of topology optimization techniques -Using continuous modeling of discrete amino acid types

The notion of optimization is inherent in protein design. A long linear chain of twenty types of amino acid residues are known to fold to a 3-D conformation that minimizes the combined inter-residue energy interactions. There are two distinct protein design problems, viz. predicting the folded structure from a given sequence of amino acid monomers (folding problem) and determining a sequence for a given folded structure (inverse folding problem). These two problems have much similarity to engineering structural analysis and structural optimization problems respectively. In the folding problem, a protein chain with a given sequence folds to a conformation, called a native state, which has a unique global minimum energy value when compared to all other unfolded conformations. This involves a search in the conformation space. This is somewhat akin to the principle of minimum potential energy that determines the deformed static equilibrium configuration of an elastic structure of given topology, shape, and size that is subjected to certain boundary conditions. In the inverse-folding problem, one has to design a sequence with some objectives (having a specific feature of the folded structure, docking with another protein, etc.) and constraints (sequence being fixed in some portion, a particular composition of amino acid types, etc.) while obtaining a sequence that would fold to the desired conformation satisfying the criteria of folding. This requires a search in the sequence space. This is similar to structural optimization in the design-variable space wherein a certain feature of structural response is optimized subject to some constraints while satisfying the governing static or dynamic equilibrium equations. Based on this similarity, in this work we apply the topology optimization methods to protein design, discuss modeling issues and present some initial results.

Three-Dimensional Unsteady Flow With Heat and Mass Transfer Over a Continuous Stretching Surface

A numerical solution of the unsteady boundary layer equations under similarity assumptions is obtained. The solution represents the three-dimensional unsteady fluid motion caused by the time-dependent stretching of a flat boundary. It has been shown that a self-similar solution exists when either the rate of stretching is decreasing with time or it is constant. Three different numerical techniques are applied and a comparison is made among them as well as with earlier results. Analysis is made for various situations like deceleration in stretching of the boundary, mass transfer at the surface, saddle and nodal point flows, and the effect of a magnetic field. Both the constant temperature and constant heat flux conditions at the wall have been studied.

Continuous-cooling method of specific heat measurement in the temperature range 100-300 K

The authors have developed a simple continuous-cooling method to determine specific heat of liquids and solids in the temperature range 100-300 K. The technique employs very simple instrumentation and continuously records the sample temperature as it cools to the bath temperature through a calibrated heat link. They have obtained specific heat values which agree with the reported data to within 3% for the samples investigated. This method also facilitates easy detection of abrupt changes in specific heat, as demonstrated in the observation of glass transition in some organic glass-forming systems. The method is sensitive to the study of relaxing heat capacity in supercooled liquids.