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Biomedical subjects

S Koehler

Publications and source records attributed to S Koehler.

16 recordsLinked to original sources

Investigations on the kinetics of electron transfer reactions in magnetic fields.

There is a controversial debate if a magnetic field can influence the rate of electron transfer (ET) reactions. In this paper, we report kinetic measurements of the ET rate constants for the redox couples [IrCl6]2-/[IrCl6]3-, [Fe(CN)6]3-/[Fe(CN)6]4-, and [Fe(H2O)6]3+/[Fe(H2O)6]2+ in magnetic fields up to 1 T. To reduce effects arising from magnetically induced mass transport (magnetohydrodynamic effect), disk microelectrodes with a diameter of 50 microm were used in potentiodynamic (cyclic and linear sweep voltammetry) and in electrochemical impedance spectroscopy experiments. None of the investigated redox couples showed a magnetic field effect on the ET rate constant.

Journal Article↗

Spectral karyotype analysis of colon cancer cell lines of the tumor suppressor and mutator pathway.

BACKGROUND AND AIMS: Microsatellite instability (MSI) is characterized by the size variation of microsatellites in tumor DNA as compared to matching normal DNA due to defects in the mismatch repair system. To examine the chromosomal differences in microsatellite-stable (MSS) and -unstable (MSI) tumors in detail, we analyzed MSS (Caco-2, Colo-205, SW948) and MSI (HCT-15, HCT-116, LoVo) cell lines by spectral karyotyping (SKY). METHODS: SKY is a sensitive method to detect chromosome aberrations by visualizing each chromosome in a different color. Metaphases were hybridized with a SKY probe mixture. Images were visualized with the SpectraCube system and analyzed with the SKYview imaging software. RESULTS: The average number of chromosomes was 49 in LoVo, 45 in HCT-116, 46 in HCT-15, 71 in Colo-205, 89 in Caco-2 and 66 in SW-948. Three aberrant chromosomes were detected in LoVo, three in HCT-116, two in HCT-15, seventeen in Colo-205, fourteen in Caco-2 and nine in SW948. CONCLUSION: The karyotypes of MSS colon cancer cells displayed complex numerical and structural aberrations. In contrast the chromosomes of MSI colon cancer cells were mostly unaltered but displayed a few isolated numerical and structural aberrations. We speculate that these isolated aberrations may be specifically involved in the pathogenesis of MSI tumors.

Chromosome Banding↗

o-Phthalaldehyde activates the Ca(2+) release mechanism from skeletal muscle sarcoplasmic reticulum.

o-Phthalaldehyde (OPA) is a bifunctional reagent that forms an isoindole derivative by reacting with cysteine and lysine residues separated by approximately 0.3 nm. OPA inhibits sarcoplasmic reticulum (SR) Ca(2+)-ATPase activity at low micromolar concentrations and induces Ca(2+) release from actively loaded SR vesicles by activating the ryanodine receptor from fast twitch skeletal muscle. Both ryanodine binding and single-channel activity show a biphasic concentration dependence. At low OPA concentrations (<100 microM), ryanodine binding and single channel activity are stimulated, while at higher concentrations, a time-dependent sequential activation and inhibition of receptor binding is observed. Activation is characterized by a Ca(2+)-independent increase in maximal receptor occupancy. Data are presented to support a model in which Ca(2+) channel and ryanodine binding activity are enhanced due to an intramolecular cross-linking of nearby lysine and nonhyperreactive cysteine residues. OPA complexation with endogenous lysine residue(s) is critical for receptor activation.

Animals↗

Evaluation of immunological responses in patients with ovarian cancer treated with the anti-idiotype vaccine ACA125 by determination of intracellular cytokines--a preliminary report.

In a first clinical trial, 45 patients with advanced ovarian carcinoma and recurrences were treated with the murine monoclonal anti-idiotypic antibody (Ab2) designated ACA125 for active immunotherapy. The monoclonal antibody (MAb) ACA125 mimics a specific epitope of the tumor-associated antigen CA125 expressed by most malignant ovarian tumors. Patients with CA125-positive tumors are immunologically tolerant to CA125, which could be overcome by the use of an anti-idiotypic antibody as a surrogate for the tumor antigen CA125. An immunological response to the anti-idiotype ACA125 in these patients was associated with a statistically significant survival prolongation. Humoral immunity to ACA125 was assessed by induction of anti-anti-idiotypic antibodies (Ab3) directed against CA125. Using flow cytometric detection methods we observe alterations of the intracellular cytokines IFN-gamma, IL-2, and IL-4 at the single-cell level during the course of immunization. There was a strong increase of intracellular IFN-gamma and IL-2 characteristic for a Th1 cell type immune response after treatment with ACA125. A delayed induction of Th2 type response, which promotes antibody-mediated immunity by B cells, could also be detected. The understanding of the kinetics of Th1 and Th2 responses could be important to improve treatment schedules for effective immunotherapy with anti-idiotype vaccines.

Antibodies, Anti-Idiotypic↗

Do not resuscitate (DNR): analysis of the DNR act.

Due to advances in technology, physicians and patients are being faced with the issue of do not resuscitate (DNR). DNR is an order that determines whether or not cardiopulmonary resuscitation (CPR) should be administered to a critically ill person. Within the state of Oklahoma, the Oklahoma DNR act was created in order to establish regulations regarding the decision-making of when to use CPR. This Act gives rise to legal and ethical problems, which have been taken into consideration by the Oklahoma Association for Healthcare Ethics (OAHE). The following article focuses on DNR with examples of case histories and possible recommendations for improvement to the current law. Furthermore, this article sets out to show why the decision of whether or not to resuscitate should be made by the patient or their family.

Female↗

Optimal target localization for ventroposterolateral pallidotomy: the role of imaging, impedance measurement, macrostimulation and microelectrode recording.

From October 1992 through December 1996, we performed 109 ventroposterolateral pallidotomies on 104 patients with Parkinson's disease. Throughout the series, we have used the basic imaging technique described by Laitinen, utilizing impedance measurement and macrostimulation to determine the optimal target position within with the pallidum and avoid the optic tract and the internal capsule. To take advantage of the high resolution of MR imaging while compensating for potential MR distortion, we have refined our stereotactic software to accomplish effective cross-registration and reformatting of CT and MR images. By 1995, several centers were suggesting that optimal target localization required microelectrode identification of pallidal neuronal firing patterns. During 1996, we performed microelectrode recording in 13 of the 25 patients undergoing pallidotomy. We have concluded that the basic technique of Laitinen, coupled with high-resolution imaging remains the foundation for achieving effective pallidotomy. Microelectrode recording is a useful adjunct to identify hyperactive firing patterns in the internal pallidum and, coupled with impedance measurements and macrostimulation, can define the lower border of the pallidum.

Brain Mapping↗

A natural language parsing system for encoding admitting diagnoses.

Free-text or natural language documents make up an increasing part of the computerized medical record. While they do provide accessible clinical information to health care personnel, they fail to support processes that require clinical data coded according to a shared lexicon and data structure. We have developed a natural language parser that converts free-text admitting diagnoses into a coded form. This application has proven acceptably accurate in the experimental laboratory to warrant a test in the target clinical environment. Here we describe an approach to moving this research application into a production environment where it can contribute to the efforts of the Health Information Services Department. This transition is essential if the products of natural language understanding research are to contribute to patient care in a routine and sustainable way.

Diagnosis-Related Groups↗

Development and evaluation of a computerized admission diagnoses encoding system.

Hospital information systems designed to support the needs of health care professionals include patient data entered using both freetext and precoded storage schemes. A major disadvantage of freetext storage schemes is that data captured in this format can only be presented as is to the user for review tasks. In the view of many health care scientists, natural language understanding systems capable of identifying, extracting, and encoding information contained in freetext data may provide the necessary tools to overcome this weakness. This paper describes the development and evaluation of a such a system designed to encode freetext admission diagnoses. This system combines both semantic and syntactic linguistic analysis techniques. Evaluation results demonstrate the overall performance of this system to be reasonable, accurately encoding approximately 76% of admission diagnoses. Inefficiencies are primarily due to the inability of this system to generate encodings in roughly 15% of test cases. When encodings are produced, however, accuracy equals that of the current manual coding method. With further modification, this application can partially automate the coding process.

Algorithms↗

Experience with a mixed semantic/syntactic parser.

The value of the computerized medical record is derived in part from the availability of medical information in a coded form accessible to manipulation by processes designed for automated decision support, medical research, and computer assistance in the management of health care delivery. To meet these needs medical reports captured and stored as natural language documents must be encoded. Below we discuss an ongoing formative process aimed at developing a natural language understanding system for chest x-ray reports. Comparative data showing the progress of this process is presented.

Hospital Information Systems↗

Three-point transformation for integration of multiple coordinate systems: applications to tumor, functional, and fractionated radiosurgery stereotactic planning.

The accuracy of an optimized three-point transformation method and its usefulness for integrating multiple independent coordinate systems has been described. Such integration can be implemented to accomplish complex stereotactic procedures which may require the use of multiple image data sets and combinations of frame-based and frameless stereotactic systems. This report details the application of an optimized transformation for intracranial lesion biopsy and/or resection, radiofrequency pallidotomy for treatment of Parkinson's disease, and fractionated stereotactic radiosurgery in a total of 68 patients. For approach to intracranial lesions, a noninvasive definition of image coordinate systems with multiple radiodense scalp markers was cross-registered with a standard stereotactic guidance system. This method allowed for elective acquisition of stereotactic image sets without requiring head frame fixation until the time of the operative procedure. In planning pallidotomy procedures, spatial cross-registration of CT and MR image coordinates were performed to target the posteroventral pallidum. CT coordinates were defined by the standard picket fence algorithm while MR images were referenced with multiple scalp markers. The addition of MR data sets improved anatomic resolution in the regions of the basal ganglia and commissures. Fractionated radiosurgery was accomplished by cross-registration of CT, MR, and plain radiographs using BRW localizers coupled with multiple scalp markers. A daily check of target positioning was performed with the BRW angiograph localizer. The average calculated error was 2.83 mm with a standard deviation of 1.66 mm which remained within the average scan slice thickness of 3.63 mm. In all cases surgical targets were reached without complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Preliminary experience using an optimized three-point transformation algorithm for spatial registration of coordinate systems: a method of noninvasive localization using frame-based stereotactic guidance systems.

This study describes the use of an optimized three-point transformation algorithm to spatially cross-register a volumetric computerized tomographic scan or magnetic resonance image data set with the coordinate system of a stereotactic frame. This algorithm was tested for accuracy using a scanned phantom in which calculated targets, using the Brown-Roberts-Wells (BRW) frame picket-fence algorithm as a standard, could be compared to physical targets measured using a BRW arc and phantom. These target values were then compared to target values calculated with the optimized three-point algorithm. This method was used for target localization in 21 patients. Following this noninvasive localization method, the standard BRW stereotactic system was used for guidance. The application accuracy of this frameless localization technique was within the limits of the scan slice thickness in 16 of 21 cases, with an average error of 2.11 mm in an average scan slice thickness of 3.1 mm. Intracranial targets were successfully reached in all cases without morbidity or mortality. The algorithm can be customized to cross-register image data sets with the coordinate systems of a wide variety of stereotactic guidance systems. The method increases the convenience and flexibility of frame-based stereotactic guidance by providing a means of noninvasive localization that can be accomplished electively at a separate time from the guidance part of a stereotactic operative procedure.

Aged↗

A natural language understanding system combining syntactic and semantic techniques.

A large proportion of the medical record currently available in computerized medical information systems is in the form of free text reports. While the accessibility of this source of data is improved through inclusion in the computerized record, it remains unavailable for automated decision support, medical research, and management of medical delivery systems. Natural language understanding systems (NLUS) designed to encode free text reports represent one approach to making this information available for these uses. Below we describe an experimental NLUS designed to parse the reports of chest radiographs and store the clinical data extracted in a medical data base.

Bayes Theorem↗

Repeated dose administration of desmopressin acetate in uncomplicated cardiac surgery: a prospective, blinded, randomized study.

The effects of single or repeated doses of desmopressin on blood loss were examined in uncomplicated cardiac surgery, while assessing the potential for thrombogenic side effects. Seventy patients undergoing elective coronary artery bypass grafting (CABG) were studied. Patients were randomized into three blinded groups: Group I received DDAVP (0.3 micrograms/kg), IV, after cardiopulmonary bypass (CPB) and 12 hours later in the Intensive Care Unit (ICU); Group II, DDAVP (0.3 micrograms/kg), IV, after termination of CPB and saline (placebo) 12 hours later in the ICU; Group III, saline (placebo) IV after CPB and 12 hours later in the ICU. Blood loss and bleeding time decreased for Group I at 24 hours (P < 0.04) when compared to Group III; however, blood product replacement, as well as intraoperative and total blood loss at 36 hours, were not different among treatment and control groups. There were four myocardial infarctions recorded in Group I, two in Group II, and one in Group III. These differences were not found to be statistically significant. It is concluded that in routine CABG the prophylactic use of single or repeat dose DDAVP does not effectively decrease blood loss or blood product replacement.

Bleeding Time↗

Stereotactic localization and guidance using a machine vision technique.

Machine vision techniques (video cameras) can be used to determine the three-dimensional position of objects. This transformation can be accomplished with standard mathematical algorithms. Initial accuracy tests of stereotactic localization with video cameras were performed using a standard Brown-Roberts-Wells (BRW) phantom simulator coupled with the BRW angiographic localizer. Localization accuracy was within 1.5 mm. Potential applications of machine vision techniques include freehand stereotactic localization of the position and orientation of surgical instruments. With sufficient computer speed these techniques can be used for continuous monitoring of the position of instruments within the cranial vault.

Brain↗

Purification and characterization of gibberellic Acid-induced cysteine endoproteases in barley aleurone layers.

Using in series ammonium sulfate precipitation, gel filtration, and DEAE anion exchange high performance liquid chromatography, we have purified to homogeneity a protease of M(r) 37,000 secreted from barley (Hordeum vulgare L. cv Himalaya) embryoless half-seeds. This protease exists in three isozymic forms whose synthesis and secretion from barley aleurone layers was shown to be a gibberellic acid (GA(3))-dependent process (R Hammerton, T-HD Ho 1986 Plant Physiol 80: 692-697). This protease constitutes a major portion of the protease activity secreted from half-seeds between 72 to 96 hours of incubation in the presence of GA(3) as detected on activity gels containing hemoglobin as the substrate. Analysis of digestion products by urea/sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration indicated that this protease is an endoprotease, therefore it is designated as barley endoprotease-A (EP-A). Inhibitor studies demonstrated that EP-A belongs to the cysteine class of endoproteases. The optimum pH for EP-A activity was 5.0, and the temperature optimum was 45 degrees C. Comparison of cyanogen bromide generated peptide fragments and NH(2)-terminal sequence analyses of the three individual EP-A isozymes demonstrates that they are very similar to each other. The NH(2)-terminal sequence shows extensive sequence homology to the NH(2)-terminal sequence of papain and several other cysteine proteinases. We also provide evidence that EP-A is not ;aleurain,' a putative cysteine proteinase encoded by a GA(3)-induced barley cDNA clone (JC Rogers, D Dean, GR Heck 1985 Proc Natl Acad Sci USA 82:6512-6516).

Journal Article↗