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At least 721 records · Page 40Linked to original sources

On the estimation of pulmonary blood flow from CO2 production time series.

It may be possible to estimate a nominal pulmonary blood flow (Q) during an exercise stress test via the algorithm used to estimate breath-by-breath alveolar CO2 production. Recently it has been demonstrated that by relating breath-to-breath fluctuations in alveolar CO2 production to breath-to-breath fluctuations in end-tidal CO2, an optimizing parameter related to Q can be determined that can be used to process the CO2 production fluctuations and minimize their variation. However, the reported values of Q using this procedure appear to be biased low. Using a computer simulation of gas exchange, we demonstrate that the estimate of Q is biased low when the nominal lung volume used in the alveolar gas exchange algorithm is too large. Furthermore, alveolar CO2 transport is determined by an integral of alveolar CO2 over the breath time and, thus, is a path-dependent quantity. The use of end-tidal CO2 fluctuations to approximate fluctuations in this integral contributes to an error in the estimation of Q which yields estimates that are biased low. Alternatively, the use of mean alveolar CO2 fluctuations yield more appropriate Q estimates. These results suggest practical implications for estimating effective pulmonary blood flow during an exercise stress test by using breath-to-breath estimates of mean alveolar CO2.

Blood Flow Velocity↗

Computer-assisted dynamic integration of multiple medical thesauruses.

We have previously described a user-interactive rule-based computer program (Dyna-SaurI) designed for dynamic thesaurus integration, and demonstrated its efficacy on integrating dermatological subsets of the MeSH and SNOMED thesauruses. In the present study, we have refined our rules for merging and mapping multiple thesauruses and tested these rules. We then applied them with a set of optimized parameters to the integration of a third thesaurus, a subset of the International Coding Index for Dermatology, with the Integrated MeSH-SNOMED thesaurus. The parameter changes resulted in improved ranking of more specific and conceptually closer terms.

Abstracting and Indexing↗

Surface coil phosphorus-31 nuclear magnetic resonance studies of the intact eye.

The feasibility of employing the surface coil probe technique for the non-invasive study of ocular tissue metabolism by phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) in enucleated bovine, rabbit, human and rat globes is demonstrated. An assessment of individual phosphorus-metabolite contributions from ocular tissues, including the cornea, lens and iris, to the overall 31P NMR spectrum (NMR spectral acquisition parameters optimized for the lens region of the globe) was accomplished through the combination of surgical ablation and difference spectroscopy. The NMR measurements also provided tissue pH values for the lens and cornea. The strengths and limitations of the surface coil NMR method, which is particularly appropriate for in vivo metabolic studies of ocular tissues such as the lens, are discussed.

Adenosine Triphosphate↗

Modification, optimization and simplification of the spot ELISA technique for the enumeration of cells secreting anti-hapten antibodies.

We describe here a modification of the spot ELISA assay for the detection and enumeration of antibody-secreting cells. The modification increases sensitivity, convenience and simplicity while optimizing parameters of time, temperature and reagents. Laboratory reagents and 96 well microtiter plates commonly used for the standard ELISA assay are adapted for use in the spot ELISA assay. Special emphasis is placed on the detection of anti-hapten IgM or IgG production by splenocytes in response to stimulation by a range of doses of antigen. In addition, two procedures are described whereby the spot ELISA assay is altered to yield a measurable optical density: (1) the blue precipitate obtained in the spot ELISA assay is dissolved and the optical density of the resultant blue color is measured, and (2) a standard ELISA substrate is substituted for the spot ELISA substrate to yield a colored solution rather than a precipitate. Both of these are shown to correlate with spot numbers and can therefore supplement or substitute for the enumeration of spots (produced by antibody-secreting cells), thus speeding and mechanizing the assay.

Animals↗

Quantitation of Fc gamma RII mRNA in platelets and megakaryoblastic cell lines by a new method of in situ hybridization.

We have developed a highly sensitive and quantitative, non-isotopic method of in situ hybridization in which the level of probe binding to intracellular mRNA is determined using an ELISA based detection method. Highly purified cell preparations or cells from a cultured cell line are centrifuged into 96 well microtiter plates. The cells are fixed with formalin and pre-treated with Triton X-100 and Nonidet P40 before photobiotin labeled cDNA probes are applied. The biotin from the hybridization is detected using multiple applications of streptavidin and biotinylated alkaline phosphatase and then visualized by the p-NPP (p-nitrophenyl phosphate) conversion method. We have determined a number of the optimal parameters in the procedure including the effects of cell numbers per well, development times and standardization of data using ubiquitous beta-actin mRNA and poly-A+ RNA expression as controls. We have used the technique to study the level of expression of FcgR mRNA in platelets and precursors. We found that platelets and megakaryoblastic cell lines only express mRNA for Fc gamma RII. The presence of the Fc gamma RII molecules was confirmed by complementary studies using immunohistochemistry with specific monoclonal antibodies IV.3 and KB61.

Blood Platelets↗

Fetal whole-body permeability--surface area product and reflection coefficient for plasma proteins.

The transcapillary distribution of protein between the vascular and interstitial spaces largely depends on the protein permeability characteristics of the capillary membranes, i.e., the reflection coefficient and permeability - surface area product for plasma proteins. Our purpose was to estimate whole-body values for these parameters in chronically catheterized, near-term fetal sheep. Average experimental changes in plasma protein concentration, blood volume and vascular pressures following fetal hemorrhage or intravascular saline infusion were analyzed using mathematical modeling and parameter optimization techniques. The mathematical model consisted of three interacting compartments: (1) fetal blood, (2) fetal interstitium, and (3) maternal blood. We found that the mean fetal whole-body protein reflection coefficient averaged 0.61 following hemorrhage and 0.80 after intravascular saline infusions. The protein permeability - surface area product averaged 0.36 ml/min/kg for the hemorrhages and 0.70 ml/min/kg following saline infusions. The major findings are that the fetus has (1) a permeability - surface area product averaging 15 times that of the adult, (2) a protein reflection coefficient approximately 70 to 90% of adult values, and (3) the ability to decrease its capillary surface area following hemorrhage.

Animals↗

Impedance of the lower respiratory system in ducks measured by forced oscillations during normal breathing.

The lower respiratory system of 10 conscious Pekin ducks breathing normally was subjected to superimposed oscillations of 1.3 to 16 Hz by a small volume piston pump. Induced sinusoidal flow (VO) and pressure (PO) signals were measured in late expiration, when the gas flow ventilated by the animal was minimum. The modulus of the respiratory impedance was calculated as the ratio PO/VO. The values obtained at the various oscillatory frequencies were compared to those predicted on the basis of a series mechanical network model consisting of resistive, inertial and compliant elements (RIC) using a least squares non linear regression method. The experimental data fitted well the frequency response of a simple RIC mathematical model. After correcting for the effects of the endotracheal tube, the mean values +/- SE of the optimized parameters were: resistance 4.8 +/- 0.4 cm H2O . L-1 . sec; inertance: 0.05 +/- 0.01 cm H2O . L-1 . sec2; compliance: 7.7 +/- 0.5 ml . cm H2O-1; natural frequency: 8.0 +/- 0.4 Hz. It is concluded that: (1) the lower respiratory system in ducks can be closely modeled by a RIC mechanical series network model; (2) the forced oscillation method can be used to investigate avian mechanics of breathing, with the birds awake and breathing spontaneously.

Airway Resistance↗

Psychosocial adjustment after renal retransplants.

Twenty-four patients who underwent more than one kidney transplant were interviewed to assess their psychosocial adaptation. Of these 24, we found 15 patients with a functioning kidney and 9 patients with a nonfunctioning transplant who were back on hemodialysis. In both groups, approximately 50% of the patients had life satisfaction ratings of "good" and "very good." The groups differed in two respects. Those with a functioning kidney had a higher employment rate and a better sexual functioning than the group on dialysis. We found many similarities in all other scored parameters (optimism, object relationships, coping devices, psychologic functioning). Denial was commonly used by most of the patients, but the group of patients who scored "good" and "very good" on life satisfaction more frequently utilized other coping devices, such as altruism, "feeling chosen," inner control, and activity than patients with "fair" or "poor" life satisfaction.

Adaptation, Psychological↗

A simple algorithm for the solution of the multiple dosing problem.

A system theoretical approach to the general multiple dosing problem is discussed [1], which is in turn reduced to a classical parameter optimization problem. An efficient numerical algorithm based on the cyclic coordinate search method to solve the latter is explained. A flexible and user-friendly program written in standard FORTRAN which is suitable for this problem is introduced. Finally, the problem is applied to the dopaminergic substitution problem in Parkinson's disease, and the necessary input data as well as the resulting output is displayed in a sample run.

Computers↗

GGOPT: an unconstrained non-linear optimizer.

GGOPT is a derivative-free non-linear optimizer for smooth functions with added noise. If the function values arise from observations or from extensive computations, these errors can be considerable. GGOPT uses an adjustable mesh together with linear least squares to find smoothed values of the function, gradient and Hessian at the center of the mesh. These values drive a descent method that estimates optimal parameters. The smoothed values usually result in increased accuracy.

Algorithms↗

Rapid and stable gene expression in hippocampal slice cultures from a defective HSV-1 vector.

Stable transfer of genetic information into neurons is a powerful strategy to elucidate specific mechanisms of neurophysiology and to develop therapies for neurological disorders. To evaluate the optimal parameters for efficient gene delivery of defective herpes simplex virus type one (HSV-1) vectors into a specific brain region, an HSV-1 vector expressing E. coli beta-galactosidase was used to infect organotypic cultures of hippocampal slices. beta-Galactosidase was expressed as early as 2 h after infection in a dose-dependent manner as measured on immunoblots, and reached a maximum level after approximately 35 h. Expression of the RNA and the antigen was still evident after the longest time sampled (11-12 days), whereas no beta-galactosidase was ever detected in cultured slices infected with a control virus lacking the reporter gene. Hippocampal cells expressing the reporter gene outlined the contour of the neuronal cell body layers in fields CA3 and dentate gyrus; such correspondence was less evident in field CA1. Anatomical, morphological, and immunohistochemical criteria also confirmed that the majority of these infected cells were neurons. beta-Galactosidase was also detected in the somata and processes of infected interneurons. Tests for synaptic pathology associated with virus infection showed no changes in pre- and postsynaptic markers.

Animals↗

Receptor-ligand interactions measured by an improved spun column chromatography technique. A high efficiency and high throughput size separation method.

Size exclusion chromatography may under the right circumstances be an easy and powerful way to measure in solution the interaction between a receptor an dits ligand. Spun column chromatography is a fast size exclusion technique of increasing popularity, however, little information exists on the method development essential to obtain efficient separation in particular when used for analytical purposes. In this paper we describe a systematic approach to select the optimal parameters for spun column separation including a simple modification of the technique whereby the spun columns are eluted by high-speed gradient centrifugation. This modification is easy to implement and it considerably improves spun column performance. We hypothesize that the high-speed centrifugation step leads to the release of additional buffer which assists in the complete elution of excluded molecules while the gradient centrifugation helps to achieve equilibrium across the gel matrix during the elution. The new method has been used successfully for several different receptor-ligand interactions, and this paper describes a general approach on how to develop new applications of the technique.

Amino Acid Sequence↗

Correlations between the activities of semen acid phosphatase and Ca(2+)-dependent ATPase and age in different breeds of cocks.

1. The present work aims to find a biochemical criterion for evaluating the evolution of sperm according to age through the study of the ATPase activity from the spermatozoa and the acid phosphatase from the seminal plasma of cocks from three different breeds. 2. The optimal parameters of action of the cock semen acid phosphatase and the Ca(2+)-dependent ATPase from the spermatozoa were studied. 3. The substrate specificity of the semen acid phosphatase and its inhibition by tartrate, fluoride, metavanadate, molybdate and Hg2+ were also studied. 4. The two enzymes were determined from the Sussex, Golden Cornish and Plymouth Rock breeds at different ages. 5. The data lead to the conclusion that some properties of bird spermatozoa are less influenced by breed while the acid phosphatase activity, secreted in the ductus deferens is a breed characteristic.

Acid Phosphatase↗

The mouse type-III procollagen-encoding gene: genomic cloning and complete DNA sequence.

Overlapping cosmid clones were isolated that covered the entire mouse type-III collagen-encoding gene (mCol3) locus including flanking sequences approximately 40 kb upstream and 20 kb downstream from the gene. This gene was characterized initially by restriction mapping and then followed by sequencing of 43.6 kb, including 5 kb upstream from the transcription start point (tsp) and all exons and introns of the entire gene. The optimal parameters for sequencing a gene of this size were determined by sequencing 5-10-kb fragments at different ratios of random and directed sequencing, and comparing their efficiency. Based on our experience for sequencing mCol3, we have estimated that the most cost-efficient method was to achieve a twofold redundancy in sequencing by using random DNA subclones as templates for sequencing prior to initiating directed DNA sequencing to close the gaps between contiguous regions. mCol3 spans 37.6 kb from the tsp to the single polyadenylation site and contains 51 exons. The overall structure of mCol3 is similar to that of other members of the fibrillar collagen-encoding gene family. Several repetitive elements were located within the gene boundaries. Based on the nucleotide (nt) sequence, the predicted sizes of the mouse type-III collagen (mCOL3) mRNA and polypeptide are 4767 nt and 1464 amino acids (aa), respectively. A comparison of mCOL3 versus the human type-III collagen (hCOL3) showed 91% identity at the aa level.

Amino Acid Sequence↗

An afterloading 192Ir surface mold.

Patients with basal cell skin cancer can be treated with afterloading 192Ir surface molds constructed from dental wax. High activity 192Ir seeds in ribbons are distributed in the mold to uniformly irradiate the target volume. The treatment is preplanned with a treatment planning system to achieve a uniform dose distribution in the planned target volume. The implant parameters optimized include the seed strength and number of seeds, inter- and intracatheter spacing between 192Ir seeds, and the distance between the implant and treatment planes. The radioactive 192Ir strands are afterloaded in the catheters embedded in the wax mold and the position secured with buttons. The treatment area drawn on the patient surface is visually overlapped with the uniformly irradiated area sketched on the mold surface. The mold is taped to the head to secure this position. The dose rate on the surface of the mold in contact with the patient skin is measured with calibrated LiF TLD chips and is within +/- 5% of the computer preplanned dose rate value. This technique is a viable alternative to external beam treatments when daily treatments are not feasible and a dose distribution conforming to the treatment area is desirable.

Brachytherapy↗

Radiobiological speculations on therapeutic total body irradiation.

Unexpected total body irradiation (TBI) of human beings, involved in nuclear warfare or in accidents in nuclear reactors can be lethal. In the 1950s, bone marrow transplantation was discovered as a potentially life saving procedure after TBI in the dose range of 5.0 to 12.0 Gy. Since that time, deliberate or "therapeutic" TBI has been used to condition patients with a lethal bone marrow disorder for bone marrow replacement. The therapeutic ratio of TBI followed by bone marrow transplantation is small. Many potentially lethal complications can occur, such as acute TBI side effects, late TBI side effects or immunological complications of bone marrow transplantation such as graft versus host disease or graft rejection. The benefits of TBI and bone marrow transplantation are that they offer a chance for cure of previously lethal bone marrow disorders. The optimal parameters for TBI remain to be defined. The review discusses the current clinical and experimental animal data, as they relate to the future definition of less toxic TBI procedures with a better therapeutic ratio. Different TBI procedures are required for patients with malignant vs. non-malignant disorders or for patients with histoincompatible vs. histocompatible bone marrow donors.

Animals↗

The role of radiation oncology in small cell lung cancer.

Small cell lung cancer comprises a histologic subgroup of bronchogenic carcinomas distinguished particularly by a responsiveness to cytotoxic agents, and equally by a strong tendency to disseminate, both to mediastinal and distant sites. At one time considered suitable only for short-term palliation by radiation therapy, this disease is now managed by both systemic and regional approaches, typically with close integration of radiotherapy and chemotherapy. Thoracic irradiation produces modest improvements in both survival and local control in small cell lung cancer, when the clinical extent is limited to the chest. The optimal parameters of dose, treatment volume, fractionation, and temporal integration with chemotherapy are not yet defined. When the disease is more extensive radiotherapy plays a useful palliative role. New biological insights are being brought to the clinic, and have stimulated new therapeutic initiatives in the treatment of this disease. Modified radiotherapy fractionation schemes and sophisticated integration of chemotherapy and radiation therapy have resulted in further advances. In addition to improved response rates and median survivals, combined modality approaches suggest, in addition, the possibility of cured subset in cases of disease confined to the chest. The adverse effects of thoracic irradiation are manageable and the more serious can be prevented with careful attention to volume and technique. Radiotherapy offers relief of many symptoms and cost-effective palliation of metastatic lesions in most body sites. Considered as a significant problem in oncology, and apart from efforts at primary prevention, major progress in this disease is most likely to result from research focussed on the limited disease subset, which, unfortunately, consists of no more than half the incident cases. These patients have a median survival of 12-18 months, and are sufficiently numerous that it is possible to detect meaningful treatment progress in clinical trials of a reasonable size. Nevertheless, the marked advances of two decades ago, when chemotherapy first came into widespread use, are not seen today. Progress is now more likely to be seen in modest improvements in survival or tumor control rates when control and experimental regimens are compared statistically in large trials or in meta-analyses. While the evidence supports the use of thoracic radiotherapy the ideal drug combination is unknown, and there is a real need for new agents of substantially greater activity than those available today. While more rational combinations of agents may be possible, it seems likely that the limits of tolerance are being reached.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Neoplasms↗

Post-reconstruction filtering of positron emission tomography whole-body emission images and attenuation maps using nonlinear diffusion filtering.

RATIONALE AND OBJECTIVES: Positron emission tomography has been playing an important role as a quantitative molecular imaging modality to measure and image biochemical processes in vivo. The quality of positron emission tomography images may impact the accuracy of the quantitative or semiquantitative information extracted from them. MATERIALS AND METHODS: In this study, the anisotropic diffusion filtering technique was used to de-noise emission images and attenuation maps of a whole body for improving the quantitative accuracy of emission images. The efficacy of the filtering technique was shown on a hot-lesion phantom as well as on whole-body emission images and attenuation maps. RESULTS: The filtering technique showed a superb performance on images reconstructed using the iterative and the filtered back-projection reconstruction techniques. CONCLUSION: Filtering may allow the reconstruction of images with optimal parameters with respect to lesion contrast and image resolution by removing the consequential noise. An improvement of as much as six-fold may be attained. It may also improve the accuracy of the quantitative information, such as standard uptake value extracted from emission images.

Anisotropy↗