Preventing school absences due to illness.
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Biomedical subjects
Publications and source records attributed to M L Kornguth.
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The lumped constant (LC) that relates the steady-state phosphorylation rate of 2-[18F]-fluoro-2-deoxy-D-glucose (2-FDG) to that of glucose was determined in an isolated working rat heart model by direct assay of phosphorylation product formation. Five conditions were tested: 5 and 30 mM glucose without insulin, and 2, 3.5, and 5 mM glucose + 10 mU/ml insulin, all at high external work load. Hearts were continuously perfused with 2-FDG and tritiated glucose without recirculation. The steady-state production of tritiated water was used to monitor the glucose phosphorylation rate. Perfused hearts were freeze-clamped and extracted in perchloric acid, and 2-FDG-6-phosphate was separated from 2-FDG with a formate column. The accumulation of 2-FDG phosphorylation products in tissue was also determined from the slopes of the total tissue radioactivity time courses measured by external gamma-ray detection. Without insulin, the LC value decreased 18% as perfusate glucose concentration was increased sixfold (0.94 +/- 0.06 at 5 mM vs. 0.77 +/- 0.17 at 30 mM). With insulin, the LC rose from 0.33 +/- 0.03 at 5 mM to 1.19 +/- 0.05 at 2 mM glucose concentration. The trends can be interpreted in terms of the concept of control strength; the LC value rises as glycolysis becomes rate limited by transport into cells. This potential variability of the LC must be addressed in the quantitative interpretation of myocardial deoxyglucose studies.
Positron emission tomography (PET) can give quantitative local information about many processes in the intact human body, which may be useful both for basic studies of metabolic processes in health and disease, and also for diagnostic purposes in individual patients. PET is absolutely limited by the availability of suitable radiotracers. Natural substrates for metabolic processes, e.g. 11C glucose, are not generally useful; compounds with a restricted range of metabolic transformations, all of which can be distinguished kinetically, are better. Radiotracer behavior may then be describable by a fairly simple set of linear first-order rate constants (kinetic model) which can each be determined from PET scan sequences and which can be combined to give physiologically meaningful data. Three 18F compounds, which form a hierarchy of pharmacologic complexity, are briefly described: fluoromethane, for blood flow, 2-deoxy-2-fluoro-D-glucose, for glucose metabolic rates, and 16-fluoropalmitic acid, a candidate tracer for rates of long-chain fatty acid metabolism.
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[18F]1-Fluoro-2,4-dinitrobenzene (FDNB), a substrate for the detoxification enzyme glutathione-S-transferase, was prepared by 18F-Cl exchange. It was administered as a rapid bolus in the perfused working rat heart and the kinetics of the label were followed by external coincidence detection and by analysis of the coronary effluents and tissue homogenates. The data suggest that part of the extracted tracer was released, part was dehalogenated and part was reversibly incorporated into a large tissue pool of FDNB that was not a substrate for defluorination. The rates of the specific processes, estimated from the residue data, may be sensitive to changes in the glutathione detoxification system and therefore applicable to investigation of the compromised myocardium.
Production conditions are reviewed from the perspective of maximizing activity--both total and specific--of 18F as electrophilic or nucleophilic precursors, with minimal levels of interfering species. Careful target design can avoid many pitfalls, and telemetry of a few key variables can guide the way to reproducible yields, consistent with prediction. Whether this 18F is chemically reactive or refractory is determined by the care taken at each step, and dictates the final success of the labeling effort.
Consensus exists that academic inbreeding inhibits innovation and scholarly achievement. Nevertheless, schools of nursing have been--and continue to be--more inbred than other schools within the university. In a follow-up survey to Miller and Ehnes' 1977 study, inbreeding has increased slightly--more junior than senior faculty are inbred, and rapidly expanding schools are the most inbred. A comparison of two schools (one highly inbred and one less so) demonstrates that schools do not recruit faculty from other schools in their region. The paper concludes that economic pressures may force deans to hire their own graduates (reducing recruitment costs) for junior positions and pay a relatively larger sum for a few senior level outbred faculty. Thus, academic inbreeding in nursing may be both inevitable and intentional.
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The effect of several tetracycline antibiotics of human erythrocytes was examined because of previous findings that these drugs bind to erythrocyte membranes. Minocycline and cetocycline, two highly lipid-soluble analogues, but not tetracycline, induced loss of K+ from red blood cells. Loss of K+ increased linearly with time of incubation, concentration of minocycline, and temperature. The effect of minocycline was inhibited by plasma and calcium. The cells from one volunteer consistently showed an augmented response to minocycline; similar findings for family members of the volunteer suggested a dominant autosomal mode of inheritance. The only abnormality noted in the subject was mild reticulocytosis and a slightly reduced K+ content in his red blood cells. Preliminary studies did not demonstrate alterations in protein composition of his red blood cell membranes, enhanced osmotic fragility, or defects in Ca++-dependent or ouabain-sensitive (Na+-K+)-dependent adenosine triphosphatase activity. The exact site of the minocycline effect remains to be determined.
Rabbits were injected intramuscularly with gentamicin and amikacin (15 mg of base per kg), and the antibiotic levels in tissues were determined 20 h after either a single or multiple injections. Disk diffusion assays, with Bacillus subtilis ATCC 6633, were carried out both on homogenates and on supernatants deproteinized with trichloroacetic acid. Both assays indicated that the kidney is the major site of antibiotic deposition. Antibiotic levels increased after multiple doses. Gentamicin levels in other tissues were higher than those of amikacin. The assay of trichloroacetic acid-treated material was more sensitive than the assay of the total homogenate.
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Human erythrocytes have been used as a model system for the study of uptake and release of antibiotics. Penicillin G, dicloxacillin, tetracycline, and minocycline were all taken up by the cells, but each showed a characteristic ratio of distribution between the extracellular and intracellular compartments. Comparison of the penicillin analogues indicated that dicloxacillin, the more lipid-soluble compound, reached higher intracellular concentrations than did penicillin G. Use of human plasma as the incubation medium markedly decreased antibiotic uptake and enhanced antibiotic egress from preloaded cells. These effects were related to the binding of drugs to serum proteins. In vivo studies in which penicillin G was injected intravenously by bolus and was then given by constant infusion showed that intraerythrocytic concentrations of drug after 2 hr approached or exceeded those in plasma. These results can be explained, in part, by the fact that the slower rate of efflux of penicillin G from the cells than of clearance from plasma serves to maintain the high initial levels of drug for a longer period.
The interaction between human erythrocyte lysates and antibiotics was studied, and the effect of intracellular components on the activity and binding of the drugs was determined. Lysates inhibited antibacterial activity of penicillin G, dicloxacillin, tetracycline, and minocycline to about the same extent as did human plasma. Dicloxacillin activity was the most inhibited, followed by the activities of penicillin G, minocycline and tetracycline. All four antibiotics bound to human hemoglobin, as determined by gel filtration methods. Heme-free globin was also effective in binding the antibiotics. In addition, minocycline and tetracycline were bound to another erythrocytic protein, which, on the basis of electrophoretic mobility, molecular size, and localization, has been identified as carbonic anhydrase. Experiments with pure preparations of carbonic anhydrase revealed that the C isozyme is the major binder of the tetracyclines and that zinc is required for binding. Tetracyclines did not inhibit enzymatic activity of carbonic anhydrase.
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The frequently absent child is most likely to be a girl of minority status whose family uses a public health clinic for services and is on Medicaid. Those students whose main source of health care was the school clinic had fewer absences due to illness.