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[Mathematical analysis in the prognostic determination of survivorship in patients with urothelial tumors of the upper urinary tract].

Mathematical analysis of the probable five-year survivorship is performed in patients operated on for neoplasms involving the urothelium lining the upper urinary tracts. The prognosis groups thus obtained are compared with the results of 5- to 10-year-long observation on the postoperative survival in fourty-one patients. It is established that the anticipated survivorship is determined with a high-degree probability by resorting to the mathematical method described.

Adult↗

[The assessment of microcirculation based on mathematical models of the hydrodynamics and oxygen transport in the microvessels (II)].

Our previous communication No. 1 presents a mathematical definition of dynamic hematocrit and rate of erythrocyte movement, based on microvessel hemodynamics model. Now we offer a mathematical model of convective diffusion oxygen transfer in the erythrocytic cylinder-plasma system. Another definition of erythrocyte movement rate is offered and a solution of two equations which permitted its definition by measured parameters. A series of practical formulae for estimating microhemodynamics is derived, which can be used in clinical practice. The proposed model has been used in cardiosurgery department of Research Center of Surgery.

Biological Transport↗

[Comparison between two diagnostic methods of computer's mathematic model and clinical diagnosis on TCM syndromes of rheumatoid arthritis].

Based on the test result of 14 trace elements in hair of 163 cases of rheumatoid arthritis, we used one of the methods of the computer's mathematic model, DYNAMIC to assign the patients to five groups among multidimensional space. Then, another method, M-DEC was used to diagnose it back on one plane. The result was compared with that by the usual clinical diagnosis, also five groups were obtained, the group of Deficiency of both Liver and Kidney, syndrome of intermingled Cold with Heat, Deficiency of Qi and Yin, syndrome of Dampness-Heat stagnating in collaterals and syndrome of Phlegm-Dampness stagnating in collaterals. And Kappa was 0.77, greater than 0.6. It displayed the consistency in observation of these two methods, which was shown reliable. After that, we have detected the sensitivity of the syndrome diagnosis by computer's mathematic model method, the result was 96.67% and the specificity of that was 95.15%. So we consider this method could give us an objective judgment on TCM syndromes of rheumatoid arthritis.

Adult↗

Using mathematical programming to assess the relative performance of the health care industry.

Unlike conventional methods for evaluating program efficiency, a recently developed mathematical programming technique, Data Envelopment Analysis (DEA), is able to handle multiple inputs and outputs simultaneously without assigning arbitrary weights and does not require the use of homogeneous measurement units nor a prespecified functional relationship between inputs and outputs. Despite of its unfamiliarity to health care researchers and administrators, this technique is becoming increasingly popular as a means of evaluating relative performance in not-for-profit entities.

Decision Making, Organizational↗

A mathematical model for the generation and control of a pH gradient in an immobilized enzyme system involving acid generation.

An optimal pH control technique has been developed for multistep enzymatic synthesis reactions where the optimal pH differs by several units for each step. This technique separates an acidic environment from a basic environment by the hydrolysis of urea within a thin layer of immobilized urease. With this technique, a two-step enzymatic reaction can take place simultaneously, in proximity to each other, and at their respective optimal pH. Because a reaction system involving an acid generation represents a more challenging test of this pH control technique, a number of factors that affect the generation of such a pH gradient are considered in this study. The mathematical model proposed is based on several simplifying assumptions and represents a first attempt to provide an analysis of this complex problem. The results show that, by choosing appropriate parameters, the pH control technique still can generate the desired pH gradient even if there is an acid-generating reaction in the system.

Acids↗

Mathematical prediction of ileal pouch capacity.

Restorative proctocolectomy is an operation still in the stage of development. Three main types of ileal pouch construction are used, but the advocacy of each probably arises more from familiarity and convenience than from scientific considerations. Since, other things being equal, pouch capacity can be expected to affect stool frequency, it seemed reasonable to examine calculable pouch capacity geometrically for different methods of construction. A mathematical model was therefore used to compare the double loop ('J') type with the quadruple loop ('W') construction. The W was estimated to have a capacity more than half as great again as the J. Similarly anastomotic methods which encroach on the ileal circumference by creating an inverted edge can be expected to reduce resultant capacity by 10 per cent or more.

Colectomy↗

Investigation of artificial biomembrane systems in biopartitioning micellar chromatography by method of mathematical design.

An attempt to create and study an artificial membrane system was realized via biopartitioning micellar liquid chromatography. Towards this end the known formula of membrane permeability (on the basis of Fick's diffusion equation) was modified so that membrane permeability may be estimated in terms of chromatographic characteristics. The two-factoral experiments on the basis of mathematical design of second order were carried out. The regression equations are derived which describe the dependence of membrane permeability on the concentration of polyoxyethylene (23) lauryl ether in the mobile phase and its flow-rate for compounds with biomedical significance. Some regularities were revealed, which characterize the permeability of compounds of the different nature through membranes. The extremal dependence (with passing through minimum) of permeability on the concentration of non-ionic surfactant was observed for anionic compounds. The increasing character of permeability in relation with flow-rate of mobile phase was recognized for cationic samples. Both dependences were basically fulfilled for zwitterionic compounds.

Anions↗

An application of mathematical morphology to analysis of the size and shape of nuclei in tissue sections of non-Hodgkin's lymphoma.

Using principles from the theory of mathematical morphology, a semiautomatic analysis of the size and shape of cell nuclei on tissue sections was carried out on a Leitz Texture Analysis System (Leitz-TAS). The four parameters proposed here are more discriminatory than conventional shape evaluation by the form factor (FF), which is based on the ratio of perimeter squared to area. The parameters quantified, respectively, nuclear elongation (ND), narrow (R1) and wide (R2) irregularities, and the distribution of R1 and R2 along the nuclear contour (ID). The properties of these parameters were tested nucleus-by-nucleus on 24 nuclear models. The methodology was then illustrated by a study of lymph node nuclei in non-Hodgkin's lymphoma (NHL). Prior to analysis, 45 lymphomas were classified into five categories of nuclear size and shape according to the International Working Formulation (IWF). Two hundred nuclei were measured on each lymph node section. Statistical interpretation was based upon an analysis of the nuclear surface area on sections and upon the mean values of R1, R2, and ND, the standard deviations of R1 and R2, and the percentage of cleaved nuclei detected by ID. The mean value of R2 discriminated best between the two sets of populations with regular and irregular nuclear contours, respectively. Parameters R1, ND, and ID permitted the distinction of certain NHL cases among populations with irregular nuclei. Nuclear invaginations decreased in depth as the nuclear area became greater. The median surface area was well correlated to the IWF, and the skewness coefficient (third statistical moment of the nuclear surface area distribution) was related to the number of nuclear size or shape subpopulations.

Analog-Digital Conversion↗

Correction of cellular autofluorescence in flow cytometry by mathematical modeling of cellular fluorescence.

A method for the correction of background fluorescence in flow cytometry with special relevance to the quantitation of low levels of cellular surface membrane antigens is presented. The method is based on the mathematical modeling of cellular fluorescence distributions of background fluorescence (autofluorescence control or irrelevant antibody control) and total fluorescence (positively stained cells). Algorithms based on two models and utilizing only the routinely available background and total fluorescence histograms are developed and implemented in computer programs. These allow estimation of the fluorescence histogram corresponding exclusively to immunofluorescence staining of the cell surface antigen of interest. Thus, the correction of background fluorescence is effected solely with software processing of routinely available data; no additional hardware or parameter determinations are necessary. Two models were chosen to be physically plausible and to represent extremes in correlation between background and probe fluorescence. Extremes were chosen to assess the solution dependence on model and to provide bounds to the actual solution when no information on correlation is available. Results are presented for both computer simulations and for an actual assay of the CR1 complement receptor on human erythrocytes to test and illustrate the technique. Alternatively, data can be tested assuming a particular model to explore the relationship, if any, between specific and nonspecific fluorescence.

Algorithms↗

Germinal center analysis with the tools of mathematical morphology on graphs.

Only few studies devoted to quantitative analysis of tissue architecture have been performed. The analysis of neighborhood relationships between cells, using graphs and mathematical morphology (MM), constitutes one approach. We propose to analyse quantitatively the architecture of a tissue with the tools of MM on graphs. The use of graphs seems best suited to take into account the neighborhood relationships between cells, independently from their mutual distances: two cells are considered as neighbors if no interfering cell is placed in a given sense between them. Such neighboring cells are linked by an arc in a graph. On such a graph, all tools of MM may be applied. We investigate two of them in the present work: (1) the distance transforms permits to analyse the repartition of a cellular population A relative to population B, (2) the size distribution permits to analyse the tendancy of a cell population to form clusters. We have applied this method using Gabriel's graph, derived from the Voronoï diagram, to determine the "zone of influence" of a cell. We have analysed the neighborhood relationships between cells in germinal centers (GC) from lymph nodes. Twelve hyperplastic GCs from follicular hyperplasia (FH) and 5 neoplastic GCs from small cleaved cell follicular lymphoma (++SCCFL) have been studied; 2 microns hematoxylin-eosin plastic embedded sections have been analysed. Cell nuclei have been identified manually by the observer by giving a numerical and image color code. Gabriel's graphs have been constructed with all centrofollicular cells. Subgraphs with only lymphoid cells, large cells or small cleaved cells have also been studied. The application of MM transformations on the graphs using software package Morphograph has allowed a quantitative description of cell distribution in the tissue. The distances of centrofollicular lymphoid cells from the periphery of the GCs (mantle zone), from nonlymphoid cells as macrophages located within the GCs and between large lymphoid cells and small lymphoid cells have been determined in FH and SCCFL. Using iterative closings and openings, we have detected aggregates of small and large cells and characterized their size and distribution in the GCs. The application of this method on lymph node biopsy has allowed a quantitative description and comparison of GCs in different pathological conditions.

Biopsy↗

Mathematical description of electrophoretic separation of weak acids by means of an H+ pulse.

The paper gives a detailed theoretical description of the recently published principle of separation by a dynamic pulse in zone electrophoresis. The theory is illustrated by using a system in which weak acids are separated by migrating against an H+ pulse. The mathematical description pertains to (i) the evolution and migration of the concentration profile of the H+ pulse, and (ii) the migration of a sample substance (here a weak acid) against and through the pulse. As a result the migration (detection) times of the separated sample components are obtained. Based on the theory, a graphical treatment was developed which allows fast optimization of the separation conditions by observing (on the PC monitor) how the trajectories of the substances (drawn in a time vs. distance coordinate system) change with a change in the parameters of the pulse. Some of the results illustrate the possible advantages of using the dynamic pulse method in analytical practice.

Acids↗

A unified mathematical model for diffusion from drug-polymer composite tablets.

The derivation and experimental verification of a unified mathematical model for the estimation of drug release rate from drug-polymer composite tablets are presented. Cylindrical coordinates are utilized in the solution of the diffusion equation for a three-dimensional system. The model is applicable to tablets that range from the shape of a flat disk (radius greater than thickness) to that of a cylindrical rod (radius less than thickness). The general solution for the fraction of drug released at a time t is (see article). This approach to a three-dimensional system, utilizing cylindrical coordinates, presents a comprehensive method for the estimation of drug release rates from sustained release tablets with drug distributed homogeneously throughout a polymer matrix. The calculated and experimental drug diffusion rate of pyrimethamine from pyrimethamine-silicone rubber composite tablets that range in shape from that of a disk to a cylinder, and of hydrocortisone from EVA, polycaprolactone, and PVA terpolymer, are compared.

Caprolactam↗

Changes in the shape of the developing vertebrate nervous system analyzed experimentally, mathematically and by computer simulation.

Two forces are necessary and sufficient to produce the transformation of the newt neural plate from a hemispheric sheet of cells one cell thick to a keyhole shape. These forces are: (1) a regionally programmed shrinkage of the surface of the neural plate (accomplished by contraction of the apical surfaces of the neural plate cells and elongation of these cells perpendicular to the plate); and (2) displacement of the whole sheet caused by elongation of either the notochord or the overlying neural plate cells in the antero-posterior direction. A computer simulation and mathematical analysis ("morphodynamics"), together with experiments and observations on embryos, were used to deduce the morphogenesis of the neural plate from these forces.

Animals↗

Solution-solubility dependency of controlled release of drug from polymer matrix: mathematical analysis.

Two types of drug release mechanisms-matrix controlled (Q - t1/2 relationship) and partition controlled (Q - t relationship)-were reported previously. The dependency of the transition between these two processes on the solution solubility of drug is now analyzed. Mathematical expressions are derived to treat the systemic effects of the addition of varying volume fractions of the cosolvent system on the concentration gradients across both the drug depletion zone and hydrodynamic diffusion layer as well as on the partitioning behavior at the polymer-solution interface. The results are in excellent agreement with reported experimental observations.

Delayed-Action Preparations↗

Mathematical model for the selective deposition of inhaled pharmaceuticals.

To accurately assess the potential therapeutic effects of airborne drugs, the deposition sites of inhaled particles must be known. Herein, an original theory is presented for physiologically based pharmacokinetic modeling and related prophylaxis of airway diseases. The mathematical model describes the behavior and fate of particles in the lungs of adult human subjects under various breathing conditions. Their deposition patterns are calculated via superposition of the separate but not independent processes of inertial impaction, sedimentation, and diffusion. The related computer code is designed to calculate total and compartmental (tracheobronchial and pulmonary) distributions of inhaled aerosols. In this manuscript, the model is first tested via comparisons of predicted deposition patterns with laboratory data from human inhalation exposure experiments and then it is applied to determine which factors most influence the dosimetry of inhaled particles. In this format, deposition patterns are explicitly related to particle characteristics, ventilatory parameters, and intersubject variabilities of lung morphologies. The dosimetric model was developed to improve the efficacy of aerosol therapy via the selective deposition of inhaled pharmaceuticals at prescribed lung locations to elicit optimum effects.

Administration, Inhalation↗

Significance of viable skin layers in percutaneous permeation and its implication in mathematical models: theoretical consideration based on parameters for betamethasone 17-valerate.

The role of viable skin layers (viable epidermis and dermis) is examined by the three-layer model using parameter values for betamethasone 17-valerate. The mathematical three-layer diffusion model indicates that the lag time and half-life after vehicle removal in epidermis and split-thickness skin are longer than those in stratum corneum without viable layers, even if drug flux at steady-state is minimally altered. The theoretical values of the lag time and half-life predicted for epidermis and split-thickness-skin samples are compatible with the values observed in another in vitro study. The results predicted by the three-layer model indicate that the simplified model (single-layer or compartment model), which regards the whole skin as one diffusion layer or one compartment, may be warranted because all three skin layers have the same half-life after vehicle removal. The parameters used in the simplified model are estimated from some of the following values directly obtainable in the experiment: flux from skin and amount in the whole skin at steady-state, lag time, and drug concentration or amount maintained to be unchanged in the donor site. However, the simplified model often cannot resolve some discrepancy between the data and model (e.g., the ratio of the half-life to lag time) even if the data may be explained by the three-layer model.

Betamethasone Valerate↗

Mathematical model and dimensional analysis of glycocholate binding to cholestyramine resin: implications for in vivo resin performance.

In large doses, cholestyramine resin lowers blood serum cholesterol by binding bile salts in the intestinal lumen and thus increases the fecal excretion of bile salts. In order to gain a better understanding of the low in vivo potency of cholestyramine, mathematical models estimating the amount of glycocholate bound per gram of cholestyramine and the free glycocholate concentration were derived and employ the capacity-corrected molar selectivity coefficient. Predictions of the quantity of glycocholate bound per gram of cholestyramine and of the free glycocholate concentration matched observed values (r2 = 0.993 and r2 = 0.998, respectively) over a wide range of conditions. Simulated binding studies indicated the relative importance of several biopharmaceutical parameters for improved resin in vivo performance. Increasing resin selectivity of glycocholate over chloride has greatest therapeutic impact if bile salt sequestering is most important in the upper portion of the intestines. Furthermore, ion exchange phenomena was subjected to dimensional analysis and revealed the controlling factors as components of two dimensionless numbers, GC* and Cl*. Placing physiologic limits on values of GC* and Cl* suggests requisite selectivity properties of more potent bile acid sequestrants and dosing strategies to optimize current resin therapy.

Binding Sites↗

Encoding of anisotropic diffusion with tetrahedral gradients: a general mathematical diffusion formalism and experimental results.

A diffusion imaging method with a tetrahedral sampling pattern has been developed for high-sensitivity diffusion analysis. The tetrahedral gradient pattern consists of four different combinations of x, y, and z gradients applied simultaneously at full strength to uniformly measure diffusion in four different directions. Signal-to-noise can be increased by up to a factor of about three using this approach, compared with diffusion measurements made using separately applied x, y, and z gradients. A mathematical formalism is presented describing six fundamental parameters: the directionally averaged diffusion coefficient D and diffusion element anisotropies eta and epsilon which are rotationally invariant, and diffusion ellipsoid orientation angles theta, phi, and omega which are rotationally variant. These six parameters contain all the information in the symmetric diffusion tensor D. Principal diffusion coefficients, reduced anisotropies, and other rotational invariants are further defined. It is shown that measurement of off-diagonal tensor elements is essential to assess anisotropy and orientation, and that the only parameter which can be measured with the orthogonal method is D. In cases of axial diffusion symmetry (e.g., fibers), the four tetrahedral diffusion measurements efficiently enable determination of D, eta, theta, and phi which contain all the diffusion information. From these four parameters, the diffusion parallel and perpendicular to the symmetry axis (D and D) and the axial anisotropy A can be determined. In more general cases, the six fundamental parameters can be determined with two additional diffusion measurements. Tetrahedral diffusion sequences were implemented on a clinical MR system. A muscle phantom demonstrates orientation independence of D, D, D, and A for large changes in orientation angles. Sample background gradients and diffusion gradient imbalances were directly measured and found to be insignificant in most cases.

Animals↗