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At least 1,711 records · Page 95Linked to original sources

Local delivery system of immune modulating drug for unresectable adenocarcinoma: in vitro experimental study and in vivo animal study.

The purpose of the study was to evaluate the efficacy and safety of a developed drug delivery system containing OK-432 through in vitro and animal study. An OK-432-impregnated polycarbonate/polyurethane stent membrane was used to develop a drug delivery system (DDS) enabling the locoregional release of OK-432. Polyethyleneglycol was used as a detergent and porosity generator. The stability of OK-432 in solvent, releasing kinetics of drug, and cytotoxicity of the DDS were evaluated. OK-432-impregnated DDS was implanted in mice in which a human adenocarcinoma cell line was injected and grown in their back. Flow cytometry and enzyme-linked immunosorbent assay were used for quantifying the amount of drug. OK-432 exposed to phosphate-buffered saline and OK-432 exposed to N,N-dimethylacetamide showed similar results on dot graphs and histograms. However, OK-432 exposed to tetrahydrofurane showed different dot graphs and histograms, which means that the antigenicity of the drug was changed. The release rate of OK-432 was maintained at a constant level for 6 weeks. The local delivery of OK-432 was found to have an antitumor effect on a human adenocarcinoma cell line in an animal study, but no effect on this cell line in in vitro cell culture. Histologic examination showed minimal inflammatory reaction in surrounding tissue. Our study shows that local treatment using this OK-432 release system is safe and effective in reducing adenocarcinoma in a mouse model.

Adenocarcinoma↗

[Scientific evaluation and quality assurance in refractive surgical interventions. Evaluation of the Datagraph med computer program].

BACKGROUND: During recent years refractive surgical procedures have been increasingly used to correct refractive errors. Exact saving and assessment of pre-, intra- and postoperative results for scientific evaluation are desired and are necessary for quality management. The purpose of this investigation was to evaluate the database program Datagraph med (version 2.5) which has been developed for data processing and assessment in refractive surgery. MATERIAL AND METHODS: Pre-, intra- and postoperative data of 169 eyes treated with different refractive surgical methods (laser in situ keratomileusis, photorefractive keratectomy, laser thermal keratoplasty, phacic IOL) were collected, entered in the database and then evaluated by the above-mentioned program (with a follow-up of up to 12 months). The exactness of the Datagraph results was compared by means of manual recalculation. RESULTS: Datagraph med was able to precisely process the patient data and save them in a database. Statistics and graphs presented by Datagraph were as data has been entered. Furthermore all standard graphs requested by the international consensus for evaluation of refractive surgical data (stability, predictability, efficacy, safety and complications) could be imaged. CONCLUSIONS: Datagraph med is a helpful and precisely functioning program for processing and evaluation of refractive surgical data. It can be used for both scientific studies and for quality control. A continuous development and improvement of the program as well as the addition of statistical functions will be necessary due to the on-going progress in refractive surgery.

Adult↗

3-D imaging and quantitative comparison of human dentitions and simulated bite marks.

This study presents a technique developed for 3-D imaging and quantitative comparison of human dentitions and simulated bite marks. A sample of 42 study models and the corresponding bites, made by the same subjects in acrylic dental wax, were digitised by laser scanning. This technique allows image comparison of a 3-D dentition with a 3-D bite mark, eliminating distortion due to perspective as experienced in conventional photography. Cartesian co-ordinates of a series of landmarks were used to describe the dentitions and bite marks, and a matrix was created to compare all possible combinations of matches and non-matches using cross-validation techniques. An algorithm, which estimated the probability of a dentition matching its corresponding bite mark, was developed. A receiver operating characteristic graph illustrated the relationship between values for specificity and sensitivity. This graph also showed for this sample that 15% of non-matches could not be distinguished from the true match, translating to a 15% probability of falsely convicting an innocent person.

Australia↗

Comparison of parzen density and frequency histogram as estimators of probability density functions.

In neurobiology, and in other fields, the frequency histogram is a traditional tool for determining the probability density function (pdf) of random processes, although other methods have been shown to be more efficient as their estimators. In this study, the frequency histogram is compared with the Parzen density estimator, a method that consists of convolving each measurement with a weighting function of choice (Gaussian, rectangular, etc) and using their sum as an estimate of the pdf of the random process. The difference in their performance in evaluating two types of pdfs that occur commonly in quantal analysis (monomodal and multimodal with equidistant peaks) is demonstrated numerically by using the integrated square error criterion and assuming a knowledge of the "true" pdf. The error of the Parzen density estimates decreases faster as a function of the number of observations than that of the frequency histogram, indicating that they are asymptotically more efficient. A variety of "reasonable" weighting functions can provide similarly efficient Parzen density estimates, but their efficiency greatly depends on their width. The optimal widths determined using the integrated square error criterion, the harmonic analysis (applicable only to multimodal pdfs with equidistant peaks), and the "test graphs" (the graphs of the second derivatives of the Parzen density estimates that do not assume a knowledge of the "true" pdf, but depend on the distinction between the "essential features" of the pdf and the "random fluctuations") were compared and found to be similar.

Fourier Analysis↗

Effect of carbon dioxide on nitrification rates.

Lab-scale ideal mixed, aerated reactors were employed to test the influence of carbon dioxide (CO(2)) on the growth rate of a nitrifier community. The buffer medium used did not contain any carbon sources. Reactors were inoculated alternatively with sludge from a nitrifying membrane assisted bioreactor, reflecting autotrophic material, or with sludge from a plant having denitrification and nitrification steps, which reflects mixed heterotrophic and autotrophic material. CO(2) was added as a gas with the intake air supply. Nitrification rates were related to the CO(2) in the intake air as well as to the total inorganic carbon in the medium. The batch experiments show a relationship between CO(2) concentration and growth rate. The optimum growth rate occurred at 5 mg CO(2)/L, corresponding to 0.4% (V/V) CO(2) in the inlet air. Different CO(2) optima for autotrophic and mixed sludges were found. In the case of the autotrophic sludge, the observed optimum growth rate was about 0.47/d and the optimum for the mixed sludge was about 0.75/d. Higher CO(2) concentrations lead to a decreasing growth rate. The first part of the kinetic graph can be described by Monod kinetics. Overall, the resulting graph can be described by Haldane kinetics.

Journal Article↗

Multimodal cerebral monitoring in comatose head-injured patients.

Monitoring of comatose patients in the neurosurgical intensive care unit (NICU) is constantly extended by the development of new methods for monitoring of cerebral function, metabolism and oxygenation. To simplify the interpretation of the rising number of parameters, and to avoid data overflow, a multimodal cerebral monitoring (MCM) system has been developed for the acquisition, display, on-line analysis and recording of physiological parameters from multiple bedside data sources. This article describes the technical details and the design of this computerized data acquisition system for variable applications in clinical patient monitoring and research. A Windows (Microsoft Corporation, Redmont, Washington) platform was equipped with an analog/digital converter board. Software for multimodal cerebral monitoring was developed using LabVIEW for Windows (National Instruments, Austin, Texas), a graphical programming system. Two software modules were created: One for the automatic acquisition of data, display of time dependent trend graphs, processing of on-line histograms, special functions for research, and storage of data in compatible format. The other module serves as an off-line monitor to display recorded data in various modalities. The MCM system has been used in 30 comatose patients with severe head injury. Mean time of MCM is 5.3 days (+/- 2.8 days), resulting in a total running time of the system of about 3800 hrs. Hardware and software proved to run stable and safe. The MCM system has become a valuable tool for monitoring of comatose patients. The simultaneous display of trend graphs of various monitoring parameters and the online processing of histograms improved the survey of the patient's condition in the ICU. Recorded data were analysed offline and contribute to a consecutively increasing data bank.

Brain Injuries↗

The compressed feature matrix--a fast method for feature based substructure search.

The compressed feature matrix (CFM) is a feature based molecular descriptor for the fast processing of pharmacochemical applications such as adaptive similarity search, pharmacophore development and substructure search. Depending on the particular purpose, the descriptor may be generated upon either topological or Euclidean molecular data. To assure a variable utilizability, the assignment of the structural patterns to feature types is arbitrarily determined by the user. This step is based on a graph algorithm for substructure search, which resembles the common substructure descriptors. While these merely allow a screening for the predefined patterns, the CFM permits a real substructure/subgraph search, presuming that all desired elements of the query substructure are described by the selected feature set. In this work, the CFM based substructure search is evaluated with regard to both the different outputs resulting from varying feature sets and the search speed. As a benchmark we use the programmable atom typer (PATTY) graph algorithm. When comparing the two methods, the CFM based matrix algorithm is up to several hundred times faster than PATTY and when using the CFM as a basis for substructure screening, the search speed is accelerated by three orders of magnitude. Thus, the CFM based substructure search complies with the requirements for interactive usage, even for the evaluation of several hundred thousand compounds. The concept of the CFM is implemented in the software COFEA. FIGURE CFM based substructure search using the compounds dopamine and benzene-1,2-diol

Algorithms↗

Minimally important change determined by a visual method integrating an anchor-based and a distribution-based approach.

BACKGROUND: Minimally important changes (MIC) in scores help interpret results from health status instruments. Various distribution-based and anchor-based approaches have been proposed to assess MIC. OBJECTIVES: To describe and apply a visual method, called the anchor-based MIC distribution method, which integrates both approaches. METHOD: Using an anchor, patients are categorized as persons with an important improvement, an important deterioration, or without important change. For these three groups the distribution of the change scores on the health status instrument are depicted in a graph. We present two cut-off points for an MIC: the ROC cut-off point and the 95% limit cut-off point. RESULTS: We illustrate our anchor-based MIC distribution method determining the MIC for the Pain Intensity Numerical Rating Scale in patients with low back pain, using two conceivable definitions of minimal important change on the anchor. The graph shows the distribution of the scores of the health status instrument for the relevant categories on the anchor, and also the consequences of choosing the ROC cut-off point or the 95% limit cut-off point. DISCUSSION: The anchor-based MIC distribution method provides a general framework, applicable to all kind of anchors. This method forces researchers to choose and justify their choice of an appropriate anchor and to define minimal importance on that anchor. The MIC is not an invariable characteristic of a measurement instrument, but may depend, among other things, on the perspective from which minimal importance is considered and the baseline values on the measurement instrument under study. A balance needs to be struck between the practicality of a single MIC value and the validity of a range of MIC values.

Health Status Indicators↗

EZ-FIT: a practical curve-fitting microcomputer program for the analysis of enzyme kinetic data on IBM-PC compatible computers.

EZ-FIT, an interactive microcomputer software package, has been developed for the analysis of enzyme kinetic and equilibrium binding data. EZ-FIT was designed as a user-friendly menu-driven package that has the facility for data entry, editing, and filing. Data input permits the conversion of cpm, dpm, or optical density to molar per minute per milligram protein. Data can be fit to any of 14 model equations including Michaelis-Menten, Hill, isoenzyme, inhibition, dual substrate, agonist, antagonist, and modified integrated Michaelis-Menten. The program uses the Nelder-Mead simplex and Marquardt nonlinear regression algorithms sequentially. A report of the results includes the parameter estimates with standard errors, a Student t test to determine the accuracy of the parameter values, a Runs statistic test of the residuals, identification of outlying data, an Akaike information criterion test for goodness-of-fit, and, when the experimental variance is included, a chi 2 statistic test for goodness-of-fit. Several different graphs can be displayed: an X-Y, a Scatchard, an Eadie-Hofstee, a Lineweaver-Burk, a semilogarithmic, and a residual plot. A data analysis report and graphs are designed to evaluate the goodness-of-fit of the data to a particular model.

Enzymes↗

Interaction of alpha-lactalbumin with dimyristoyl phosphatidylcholine vesicles. I. A microcalorimetric and fluorescence study.

alpha-Lactalbumin and dimyristoyl phosphatidylcholine were used as a prototype to study the influence of a protein conformational change, induced by the pH, on the interaction between that protein and a phospholipid. The enthalpy changes associated with the interaction of alpha-lactalbumin with dimyristoyl phosphatidylcholine vesicles were measured as a function of the molar ratio of phospholipid to protein, pH and temperature. Gel-filtration, electron-microscopic and fluorescence data for the same experimental conditions were also obtained. At pH 4 and 5, the enthalphy changes (delta H) are not only larger than at physiological pH, but also show a maximum at aobut 23 degrees C in the delta H vs. temperature graph. At pH 6 and 7, on the contrary, delta H increases with decreasing temperature without a maximum in the curve. Gel-chromatographic and electron-microscopic data show that at pH 6 and 7, the morphological characteristics of the vesicles are unchanged upon addition of alpha-lactalbumin, while at pH 4 and 5 at 23 degrees C an extra peak appears in the gel-filtration graphs between the pure vesicles and alpha-lactalbumin. The new fraction contains lipid-protein complexes. Electron micrographs show that bar-shaped entities are formed. A red shift at 23 degrees C and a blue shift at 37 degrees C, both to 336 nm, are observed for lambda max of the fluorescence emission spectra at pH 4 when alpha-lactalbumin is brought into contact with the phospholipid. At the same time, a strong increase in the fluorescence intensity is observed. The chromatographic and fluorescence data indicate that a lipid-protein complex with a molar ratio of approx. 80 is formed. At pH 7 and different temperatures, the emission maximum remains at the wavelength of pure alpha-lactalbumin, the change in the fluorescence intensity, however, indicates that interaction with the lipid occurs. The results can be explained on the basis of an electrostatic interaction at pH 6 and 7, and a hydrophobic interaction at pH 4 and 5.

Calorimetry↗

The 'knotting' problem in proteins. Loop penetration.

The 'knotting' problem in proteins is redefined in terms of the more general concept of loop penetration. Disulfide-containing proteins are represented as linear graphs, and it is proposed that proteins with nonplanar graph representations display loop penetrations in their three-dimensional structure. With this argument, it is shown that the occurrence of loop penetration in disulfide-containing proteins is approximately that expected based on the random pairing of sulfhydryl groups. It is argued that loop penetration is not as rare as currently held.

Disulfides↗

Sensitive quantitation of carcinoembryonic antigen in cerebrospinal fluid and its barrier-dependent differentiation.

Modification of an enzyme immunoassay using beads as solid phase allows the detection of 3 pg/ml carcinoembryonic antigen (CEA). The beads are shown to be advantageous for the extraction of proteins in highly diluted antigen solutions thus replacing a need for concentration of the sample. The mean concentration of CEA in pooled cerebrospinal fluid (CSF) from 120 control persons was shown to be 2.7 pg/ml. The mean of the CSF/serum concentration quotients of CEA was 0.0015 for normal blood CSF barrier function with a corresponding mean albumin CSF/serum quotient of 0.0048. From the ratio of these two quotients (QCEA/QA = 0.31) and the corresponding biological variation we constructed the normal range of an evaluation graph. In the range of a blood CSF barrier dysfunction, the discrimination line between values with or without a local CEA synthesis in brain was determined to be QCEA = 0.7 QA. Twenty-five out of 383 control persons and 29 out of 45 patients with a tumor metastasis had evaluable quotients. The evaluation graph had a high significance with respect to the identification of tumor metastasis: from a group of patients with a confirmed leptomeningeal metastasis 13 out of 13 and from a group of patients with intraparenchymatous tumor metastasis 10 out of 16 could be identified by CSF analysis. The CEA CSF/serum concentration quotient fits well in the concept of a molecular size-dependent filter function of the blood CSF barrier.

Blood-Brain Barrier↗

An automaton computer program for a microcomputerized real-time (thesaurus based) abstract medical record.

A study of the key wordings used by the doctors in medical records in ICU preceded this implementation; they constitute a thesaurus (2700 strings) organized in 2 trees. These strings are proposed along the dialogue which occurs between the microcomputer and the user; on these bases, several graphs allows movement in the tree by minimization of the pathway. The use of the thesaurus with the corresponding graphs necessitates only one automaton program. This medical data microcomputerized system is transparent for the user, thanks to a multilayered software. In the external layer the microcomputer provides access to the system by one of the following function keys: creation of a medical record, additional information on a medical record already known, research of a medical record, listing of the open medical records, printing of a medical record. Each one of these function keys provides access to the following 5 chapters: identity, antecedents, reasons for admission, evolution, destiny; these chapters use parameterized procedures. This software is implemented on a low-cost microcomputer fitted with a dual drive disk (170 kilobytes each) and a printer (90 characters/s).

Computers↗

On the identification of verbs in computer programs of physiological models.

The rationale for identifying verbs (actions modeled) in the source code of a mathematical model is presented, with algorithms leading to computational techniques for devising explanations of such models. Using flow graph methodology the source code of a program can be described as disjoint intervals of its directed acyclic graph. Intervals of this set containing complete loops represent the code structure conceptually equivalent to verbs modeled. In turn, such structures can be mapped uniquely as functional dependencies of the intensional form of a relational data base which is the model output. Simulation, then, can be viewed as retrieval, and the logical inferences of a model appear to be derivable via relational algebra of the data base. In these terms, a verb is a relation consisting of at least one variable defined in an interval. The relation's key attributes must include at least one variable, also defined in the interval. Verb definitions are essential if programs are to explain themselves.

Computers↗

Microcomputer-based analysis of cardiovascular indices.

A microcomputer-based program has been developed which performs rapid and accurate acquisition of cardiovascular data from instrumented animals or isolated perfused hearts with concurrent analysis and display of the hemodynamic indices. The system allows real-time viewing of the data in four alternative graphic displays. These include: (1) a strip-charge type display of all channels; (2) a full screen display of any single channel; (3) display of pressure-segment length; and (4) trend graphs (cumulative change with time) of calculated hemodynamic indices such as heart rate, systolic and diastolic blood pressure, percent change in myocardial segment length, mean blood flow and percent change in arterial diameter. Precise analysis of both transient and steady-state events may be performed on any segment of data stored on the hard disk. The data at any point in the experiment may be accessed by cursoring through any trend graph of the derived indices, by recalling special event markers or by using the automatic time markers. The calculated results are printed and stored in ASCII files which can be transferred to spreadsheets, databases, graphics or statistical programs.

Animals↗

Algebraic framework of an optimization problem in diagnosis.

A formal analysis of an optimization problem in medical diagnosis is presented. The mathematical model of the diagnostic process corresponds in this work to an abstract machine definition which is based on the following sets and functions: Set of possible pathological states (diseases) of a patient, set of diagnostic tests (examination methods), set of all possible results of the tests (symptoms and signs), function which chooses successive tests, function performing a test (i.e., assigning to a given test its result), function assigning to each symptom a certain subset of the set of diseases. For a given abstract machine a class of pairs of graphs is formed; their analysis leads to the identification of a class of pairs of subgraphs which corresponds to an optimized diagnostic procedure. The optimization consists of a comparison of the distances between the initial and terminal vertices of the graphs and of a choice of a shortest route to a final diagnosis. For the considered class of pairs of subgraphs a mathematical model of the optimized diagnostic process is reconstructed.

Diagnosis↗

An improved method to evaluate the precision of computer ECG measurement programs.

We present a new graphical evaluation method aimed at displaying the main characteristics of computer ECG measurement program results. The proposed graphs provide information on the number of rejected measurements and gross program errors, and on the precision of the results, i.e. the scatter of the differences between fiducial point estimates given by the programs and the reference. 'Scatter-graphs' concerning P, QRS and T wave boundary recognition from the programs participating in the European Concerted Action on 'Common Standards for Quantitative Electrocardiography (C.S.E.)' are analysed and discussed (10 standard 12-lead ECG programs and 9 Vectorcardiographic (VCG) programs from 10 European, 5 American and 1 Japanese Centers). The method proved to be a powerful tool for a direct and global qualitative comparison of the efficiency of the algorithms elaborated by the program developers, and allowed some of the strategies adopted in these programs to be highlighted.

Algorithms↗

Grouping and linear regression.

With a large number of observations, the method of grouping is often employed to provide simpler graphs or tables. When one investigates the relationship between two variables, one usually groups based on the magnitude of the independent variable, and then plots the dependent variable averages against independent variable averages to get a clearer graph. If grouping is based on the magnitude of the dependent variable, the plot of group means as indicated above does not appropriately describe the relationship of the dependent variable to the independent variable. These results are demonstrated theoretically for the special case of bivariate normality (and thus linear regression), but would be expected to be similar for other distribution assumptions. An example is given from an epidemiological study.

Blood Pressure↗