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Publications and source records attributed to S Sparks.
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Neutrophils form CD18-dependent adhesions to endothelial cells at sites of inflammation. This phenomenon was investigated under conditions of flow in vitro using isolated human neutrophils and monolayers of HUVEC. The efficiency of conversion of neutrophil rolling to stable adhesion in this model was >95%. Neither anti-CD11a nor anti-CD11b antibodies significantly altered the extent of this conversion, but a combination of both antibodies inhibited the arrest of rolling neutrophils by >95%. The efficiency of transendothelial migration of arrested neutrophils was >90%, and the site of transmigration was typically <6 microm from the site of stationary adhesion. Approximately 70% of transmigrating neutrophils migrated at tricellular corners between three adjacent endothelial cells. A model of neutrophils randomly distributed on endothelium predicted a significantly greater migration distance to these preferred sites of transmigration, but a model of neutrophils adhering to endothelial borders is consistent with observed distances. It appears that stable adhesions form very near tricellular corners.
Ecdysteroid titres have been determined in adult female house crickets (Acheta domesticus) in relation to reproductive maturation. Ecdysteroid levels in newly emerged adult females are low except in the gut and carcass, which probably reflects the remnants of the preecdysial ecdysteroid peak. Ecdysteroid levels in all compartments increase markedly once ovarian weight surpasses 10 mg. Apolar ecdysteroid conjugates (ecdysone 22-fatty acyl esters) predominate in ovarian tissue throughout ovarian maturation, but low levels of free ecdysteroid and polar conjugated ecdysteroids are also present. During this period, two peaks of ecdysteroids (mainly free and apolar conjugated ecdysteroids) are observed in the haemolymph, gut, and carcass compartments. The peaks in the haemolymph occur when the ovarian mass reaches 30 and 100 mg. The gut and carcass may be acting as sinks or sites of metabolism for the hormone released from the ovaries. The rate of ecdysone acylation by ovaries was found to be developmentally regulated, increasing from low levels in the immature ovaries of newly emerged females as the ovaries increase in size. A semiquantitative assay has been developed to identify compounds which inhibit the conversion of [3H]ecdysone into 22-fatty acyl [3H]ecdysone by ovaries in vitro. A number of ecdysteroids possessing a free hydroxyl group as C-22 as well as the side-chain stereochemistry of ecdysone effectively inhibit this conversion, probably by acting as competitive substrates. In the cases of 20-hydroxyecdysone and ponasterone A, it was clearly demonstrated that these compounds are converted to a mixture of C-22 fatty acyl esters. Several other compounds which have been suggested to affect ecdysteroid metabolism/mode of action in other systems were also tested for their effects on the acyltransferase activity of ovaries in vitro.
Accurate enumeration of CD34+ stem cells is important in assessing the need for continued mobilization and subsequent apheresis collections. We compared two new analysis systems, ProCOUNT (Becton Dickinson Immunocytometry Systems) and IMAGN 2000 STELLer (Biometric Imaging, Inc.) with our current (3-Color) flow cytometry-based method. The ProCOUNT system uses an absolute counting tube, which contains reference beads and a specific (multiple) gating strategy to determine an absolute count. The STELLer assay combines microvolume fluorimetry and automated analysis software to determine an absolute count. To evaluate linearity and reproducibility, peripheral blood was spiked with CD34+ cells (KG1a cell line). Three dilution series (measured at approximately equal to 0, 5, 10, 25, 50, and 100 CD34+ cells/microliter) were analyzed by each method. Analysis of predicted versus actual CD34+ concentration showed excellent correlation with all methods (r2 > or = 0.97, slope 0.98-1.04). To further assess precision, two PBSC samples, at approximately 200 and 800 CD34+ cells/microliter, respectively, were analyzed 10 times by each method. Coefficients of variation for the precision analysis of these samples were 5.1%-6.4% and 5.4%-12.3%, respectively. To assess overall performance, 75 patient specimens were analyzed. Excellent correlation (r2 values of 0.89-0.98) was observed among all three methods. We conclude that the three methods provide comparable linearity and reproducibility.
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OBJECTIVE: To elucidate the glycemic response and antibody formation in gestational diabetic women treated with insulin injected by a needle or a jet. The American Diabetes Association's position statement on jet injectors raised the concern that "insulin could be denatured as a result of forceful injection through a tiny port, which could lead to an increase in antibody formation" (Diabetes Care 11:600, 1988). However, the pharmacokinetics of jet-injected insulin suggest that it might be useful in controlling postprandial glucose levels. METHODS: We randomized 20 women with gestational diabetes mellitus (< 34 wk gestation) who required insulin to receive either jet-injected or needle-injected human NPH and regular insulin. Variables of interest were evaluated at the start of therapy, weekly until delivery, and 6-wk postpartum that included: 1) insulin antibodies in the mother and her infant, 2) HbA1c, 3) insulin dose, 4) fasting and postprandial glucose levels, and 5) subject acceptance and preference. RESULTS: Of the 10 women in the needle group, 6 developed significant insulin antibodies compared with 1 of 10 in the jet group (P < 0.001). HbA1c and insulin doses were the same in both groups. During the test meal, glucose levels in the jet group were significantly lower (P < 0.01), yet none of the women in the jet group experienced blood glucose < 70 mg/dl (3.89 mM) at 3-4 h after the meal, compared with 5 in the needle group (P < 0.001). Jet injection was associated with less variability (P < 0.001) in postprandial glucose values but slightly greater variability (P < 0.05) in fasting glucose. Jet-injected insulin was more readily accepted by subjects than needle injections. CONCLUSIONS: Jet injection is associated with a diminished antibody response and postprandial variability compared with needle-injected insulin. Thus, this warrants consideration as a therapeutic option for women with gestational diabetes mellitus and may also be applicable to nonpregnant, insulin-requiring diabetic patients.
There are those in the medical device manufacturing industry who consider the new regulatory system in Europe to be a burden that will reduce profitability. In this article, the author makes a case for the benefits that can be gained by implementing the new procedures, particularly for the many small companies that make up the European medical device industry. By using implementation of the new system as an opportunity to take a fresh look at product development and manufacturing processes, profitability can be increased.
The reaction of hydrogen peroxide with the copper-zinc bovine-liver superoxide dismutase at low molar ratios (0.2-20.0) of H2O2/active site between pH 7.3-10.0 leads to the loss of native enzyme as a distinct form monitored by electrophoresis. The pH dependence of the loss of native enzyme between 7.3 and 9.0 indicates the involvement of a conjugate base on the enzyme of pKa of 8.7 +/- 0.1. The rate of loss of the native enzyme is first order with respect to the concentration of both enzyme and hydrogen peroxide between pH 7.3 and 9.0 with no evidence for binding of peroxide. A second-order rate constant of 3.0 +/- 1.0 M-1 s-1 is obtained from these data. At pH 10.0 the reaction is first order with respect to enzyme concentration but saturable in H2O2. All data are consistent with the interpretation that H2O2 reacts with the enzyme at the lower pH where the reaction is dependent upon the conjugate base of a functional group on the enzyme. At the higher pH, the data are consistent with the reaction of HO2- and H2O2 with the dismutase. The dissociation constant for HO2- calculated from the kinetic data at pH 10.0 is between 25-50 microM and the rate constant for the breakdown of the HO2- dismutase complex is 1.10 + 0.05 x 10(-2) s-1. The change in the electrophoretic pattern at all pH values is accompanied by the loss of the ability of the enzyme to bind copper. Weakly bound or free copper can be detected using bathocuproine disulfonate. Furthermore copper-defficient forms of the enzyme can be detected by staining gels of the peroxide-treated dismutase with diethyldithiocarbamate.
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Patients who participated in an outpatient intravenous therapy program designed to limit hospitalization for those who could be maintained on ceftriaxone at home were interviewed regarding costs and benefits. Of the 79 patients interviewed concerning 83 therapeutic episodes, 43.4 percent were able to perform their usual activities as soon as they began the program, 28.9 percent were restricted for part of the time, and 27.7 percent never resumed their usual activities. The 83 therapeutic episodes represent a total of 2,409 outpatient days (mean 29.7; standard deviation [SD] 17.7), 1,406 of which represent unrestricted activities. Costs and benefits of the program were calculated separately for four employment groups: not employed; usually employed, but not while on intravenous therapy; employed while on intravenous therapy, with time off for follow-up visits; and employed while on intravenous therapy, no time off for follow-up required. The mean total benefit, weighted across all four groups, was $6,588.14 (SD = $3,802.90) per patient. Mean weighted costs totalled $1,768.02 (SD = $1,129.36). The overall weighted benefit/cost ratio was approximately 5:1. Although private insurers reimbursed 63 percent of the patients for all hospitalization costs, only 39 percent were fully covered for the follow-up physician visits required during outpatient therapy.
Measurement of red blood cell ion transport levels have become increasingly important as biological markers in psychiatric research. A major drawback to large-scale collaborative studies of red blood cell lithium transport rates has been the requirements of fresh cells and a transport research laboratory for performance of the assays. We have developed a method for the preservation of human red blood cells for up to five days with retention of lithium efflux characteristics. This method should find wide-scale application in collaborative studies of this marker in major affective disorders, in genetic studies of families living in diverse geographic locales, and in collaborative studies utilizing a centralized transport assay laboratory.
Differences in red cell sodium content and sodium-lithium countertransport were studied in black and white children with a mean age of 12 years. For both boys and girls red cell sodium content was higher in blacks and countertransport lower (P less than 0.05). For both ethnic groups red cell sodium was lower in girls than boys and a consistent positive relationship was noted between body mass index and countertransport. Despite the lower red cell Na-Li countertransport values in black compared to white children, a significant positive correlation with systolic blood pressure was found independent of adiposity. In contrast, no correlation was evident between Na-Li countertransport and blood pressure in the white children. If red cell cation transport is confirmed as a marker for hypertension, study of racial differences may help explain the twofold higher prevalence of this disease among blacks.
A program has been developed for the outpatient administration of parenteral antibiotics. To date, more than 150 patients with osteomyelitis, septic arthritis, pyelonephritis, endocarditis, and other infections have been treated. Antibiotic solutions were prepared in the hospital pharmacy and given to the patient to be kept refrigerated at home until used. Patients administered their own antibiotics by means of a heparin lock, which was replaced every four days or when necessary. Complications were infrequent. Many patients were able to return to work while receiving therapy; others enjoyed the comfort of being at home. Cost reductions were substantial, calculated to be at least $142 a day, or the charge for a semiprivate room in 1981. In addition to the cost savings, critically needed hospital beds were freed for more acutely ill patients.
Assays for red cell sodium concentration and sodium-dependent lithium efflux were studied from a methodological point of view. The technical errors for sodium concentration--based on concurrent analysis of randomized blind duplicate samples--was 2.5% and for lithium efflux 6.4%. Based on repeated measures in the same individual, the assays were stable over time and reproducible; individual differences at a mean interval of 16 days were not significantly different. A wait of two hours from time of phlebotomy to analysis yielded a slight (3.8%) but significant fall in the sodium concentration; no further change was found at four hours. No change occurred in the lithium efflux over time. A standardized breakfast containing 664 mg sodium did not affect the measurements when fasting and three-hour postprandial levels were compared. The ratios of intra- to inter-individual variance were small--0.04 for red cell sodium concentration and 0.09 for sodium-stimulated lithium efflux. These assays appear to be reproducible and stable and can be applied in large scale field trials.
1. There was a significant positive relationship between sodium-stimulated lithium efflux and systolic blood pressure (r = 0.512) in erythrocytes of black school children. Weight was also positively and significantly correlated with blood pressure. Although erythrocyte sodium concentration did not bear any significant relationship with blood pressure, it did bear significant inverse relationship with urinary sodium excretion. 2. High-school students were randomly assigned to either the experimental or the control group. In the former a reduction of about 70% in salt intake was achieved. After 24 days, the erythrocyte sodium concentration was significantly reduced in the experimental group. A non-significant decline in systolic blood pressure was observed in the experimental group; no change was detectable in the control group for either erythrocyte sodium concentration or systolic blood pressure.
Since Lejeune et al. (1963) first described the syndrome of Cri du Chat (Cry of the Cat), cases have been described in the literature in terms of genetic abnormalities. All cases were severely retarded and the mental impairment has been believed to be progressive, although no longitudinal studies have been reported. Descriptions of speech and language behavior have been scarce. This paper presents a case of a 7-yr, 6 mo-old girl with Cri du Chat who has received speech and language therapy for five years. Her speech, language, and mental development are noted and are not consistent with cases reported previously.
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