How to use entity-relationship diagrams in developing personal database systems.
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Biomedical subjects
Publications and source records attributed to F W Lee.
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The article discusses the changes in health care delivery and the advances in computer technology that have resulted in benefits to patient care but also have raised concerns for protecting the confidentiality of health information. Numerous techniques for safeguarding computer information are also presented.
Computer-aided systems engineering (CASE) is a software technology that helps systems developers write complex application programs. CASE has been identified as having the potential to help health information systems developers complete large-scale projects such as the computer-based patient record or community health information network. The article evaluates the current use of CASE in health care and other settings through a review of the literature. There is no consensus on the value of CASE. Many experts believe that it is an emerging technology that will become widespread, whereas others see it as expensive and cumbersome to use.
Intravenous infusions of nitroglycerin (GTN), 1,2-glyceryl dinitrate (1,2-GDN), and 1,3-glyceryl dinitrate (1,3-GDN) were given to four conscious dogs at 10 micrograms/min, 30 micrograms/min, 50 micrograms/min, and 70 micrograms/min of GTN and 20 micrograms/min and 100 micrograms/min of GDNs. The steady state plasma concentrations (Css) of GTN were reached after about 60 min whereas for 1,2-GDN and 1,3-GDN the Css were reached at about 150 min after the infusion began. Except for one dog, the Css of GTN were not proportional to infusion rate, however, all dogs together showed a good linear relationship between Css of GTN and infusion rates with an average correlation coefficient of 0.917 +/- 0.102. Large variability in GTN clearance after various infusion rates was observed in all dogs. The Css ratios of 1,2-GDN/GTN and 1,3-GDN/GTN yield overall averages of 31.5 +/- 17.2 and 5.47 +/- 3.19, respectively. Average Css ratios of metabolites 1,2-GDN/1,3-GDN were 5.78 +/- 1.23. This ratio is different from those obtained after iv bolus and oral dosing indicating that the biotransformation of GTN to 1,2-GDN and 1,3-GDN differs for each dosing route. The clearances for 1,2-GDN and 1,3-GDN were not changed over the dose range of 20 micrograms/min to 100 micrograms/min. Terminal half-lives of 1,2-GDN and 1,3-GDN postinfusion were similar to those values obtained after a single bolus dose (45 min). It appears that all the GTN dose at steady state can be accounted for by the formation of measurable 1,2-GDN and 1,3-GDN. Large intra- and interdog variations in systolic blood pressure decrease (SPD) following infusions of GTN were observed, however, all dogs showed a clear systolic blood pressure decrease when the highest infusion rate (70 micrograms/min) was given. No significant systolic blood pressure drop was detected following 20 micrograms/min infusions of 1,2-GDN or 1,3-GDN. It was clear that systolic blood pressure in all dogs decreased following 100 microgram/min infusions of 1,2-GDN or 1,3-GDN. When SPD values were plotted vs. log GTN concentrations following the infusion of 70 micrograms/min of GTN in all four dogs, a counterclockwise hysteresis was observed indicating the significant contribution of the active dinitrate metabolites to GTN pharmacodynamics.
Studies were carried out in conscious dogs to determine the effects of 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl dinitrate (1,3-GDN) on nitroglycerin (GTN) pharmacokinetics and pharmacodynamics. In the first set of experiments, steady state plasma levels (Css) of either 1,2-GDN or 1,3-GDN in three dogs were rapidly achieved by giving an iv bolus (77 micrograms/kg), followed immediately by an infusion (50 micrograms/min) of the same GDN. A single iv bolus dose of GTN (0.025 micrograms/kg) was given 50 min after beginning the GDN infusion and compared with plasma concentrations following a similar GTN dose in the absence of dosed GDNs. No significant differences in GTN AUC (p > 0.9) and CL(app) (p > 0.7) were found. In a second set of experiments, an infusion of nitroglycerin was begun in each of 4 dogs and continued for 160 min at an infusion rate of 100 micrograms/min. Steady state concentrations of GTN were achieved within 100 min, at which time the dog received, simultaneously, an iv bolus dose (5.14 mg) of one of the GDNs and an infusion dose (100 micrograms/min) of the same GDN. For both dinitrate metabolites no significant differences (p > 0.5) were found between control and interaction arterial and venous clearances, although venous GTN clearances tended to decrease in the presence of dosed GDNs. Steady state systolic blood pressure during GDN infusions could be further reduced when GTN doses were administered; however, the steady state systolic blood pressure decrease caused by GTN could not be further reduced by the GDN infusions. Results suggest that the GDNs do not inhibit nitroglycerin metabolism or hemodynamics at the dose levels studied here.
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In order to design a means to preclude the development of nitrate tolerance, an in vivo model of nitroglycerin (GTN) tolerance was developed in the rabbit to examine the tolerance potential of S-nitroso vasodilators. Three separate studies were performed with 54 male New Zealand white rabbits which were instrumented for chronic infusion of vehicle or of either S-nitroso N-acetylpenicillamine (SNAP) or GTN (n = 6/group). Each vasodilator was infused for 24 hr at a dose rate of 60 nmol/kg/min. Three and 24 hr after the end of the infusion, each rabbit was anesthetized with pentobarbital and instrumented to monitor blood pressure, and dose-response curves were performed using SNAP or GTN. The dose-response curves were analyzed to determine the degree of displacement of the treated rabbit's dose-response curves compared to that of the vehicle-treated rabbit. Relative to the vehicle group, the GTN dose-response curve for systolic blood pressure in the GTN-infused rabbits was dextrally shifted 25.0-fold (P less than .05); 24 hr later the dextral shift was 0.9. The corresponding shifts in the SNAP dose-response curves were 2.7- and 0.5-fold, respectively. When SNAP was infused for 24 hr, the corresponding 3- and 24-hr dextral shifts for GTN were: 7.8- (P less than .05) and 0.7-fold; for SNAP they were: 1.9- and 0.6-fold. In a third study, N-acetylcysteine was coinfused (0.14 mg/kg/min, 200 mg/kg cumulative dose) with GTN over 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
The pharmacokinetics and pharmacodynamics of nitroglycerin (GTN) and its dinitrate metabolites, 1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate (1,2-GDN and 1,3-GDN), were examined in a seven-way crossover study in six conscious dogs. The mean apparent clearance after a low GTN i.v. dose (0.025 mg/kg) was 1440 ml/min/kg (S.D. = 630), which decreased to 686 ml/min/kg (S.D. = 317) after a high GTN i.v. dose (0.25 mg/kg), demonstrating dose-dependent pharmacokinetics. Bioavailability of oral GTN (0.25 mg/kg) was very low (0.015 +/- 0.019). The formation of dinitrate metabolites was rapid and extensive after i.v. and oral dosing of GTN. The pharmacokinetics of 1,2-GDN and 1,3-GDN were very similar. The dinitrates exhibited longer half-lives (approximately 45 min) and lower apparent clearances (approximately 16 ml/min/kg) than those found for GTN. The apparent fractional GTN clearances to 1,2-GDN (CLapp,m1) and 1,3-GDN (CLapp,m2) were also determined. The CLapp,m1 decreased significantly (P less than .05) in going from the low GTN dose (1030 +/- 620 ml/min/kg) to the high dose (425 +/- 145 ml/min/kg). In contrast, CLapp,m2 remained unchanged (low dose: 107 +/- 55 ml/min/kg; high dose: 115 +/- 37 ml/min/kg). The duration of systolic blood pressure decrease after low i.v. GTN doses was very short (approximately 15 min) and significantly longer (approximately 90 min) for high i.v. GTN doses. GTN is about 10 to 12 times more efficient than 1,2-GDN and 1,3-GDN in terms of the maximal systolic blood pressure decrease produced by a therapeutic dose. Oral GTN is pharmacodynamically active and this effect can be attributed to the formation of high levels of dinitrate metabolites.
A high-performance liquid chromatographic procedure was developed for the quantitation of homoharringtonine in plasma. Harringtonine was used as an internal standard, and 1 ml of sample was required. The single-step extraction with dichloromethane resulted in almost 100% recovery for homoharringtonine and harringtonine. Analysis was performed on a reversed-phase CN column with amperometric detection. Chromatography was completed in 12 min. At an oxidation potential of +1.0 V, the detection limit was 1 ng/ml at a signal-to-noise ratio of 2. The mean analytical recovery for homoharringtonine was 99.5%. The within-run precision and between-run precision were both less than 11%. The method is equally applicable for plasma or serum, and it has been demonstrated to be applicable for study of the pharmacokinetics of homoharringtonine in patients suffering from acute non-lymphocytic leukaemia.
A sensitive gas chromatographic-electron-capture detection method for the simultaneous determination of the antianginal drug nitroglycerin (GTN) and its dinitrate metabolites (1,2-GDN and 1,3-GDN) was developed. Human plasma samples (1 ml) spiked with 2,6-dinitrotoluene as the internal standard were extracted once with 10 ml of a methylene chloride-pentane mixture (3:7, v/v). Using this solvent system, less contaminants are extracted into the organic phase from plasma, resulting in cleaner chromatograms and prolonged column life. A break point was observed on the standard curves of GTN and GDNs. The two linear regions for the detectable concentrations of GTN are 0.025-0.3 and 0.3-3 ng/ml and for 1,2-GDN and 1,3-GDN they are 0.1-1 and 1-10 ng/ml. The limits of detection by this method for GTN, 1,2-GDN and 1,3-GDN in plasma are 0.025, 0.1 and 0.1 ng/ml, respectively.
Three strains of non-flagellate Ps. aeruginosa isolated from pathological specimens have already been described. The purpose of this paper is to report further isolates. All strains have been shown to be different types isolated from a variety of infections.
Three isolates of non-flagellate Pseudomonas aeruginosa obtained from pathological material of human cases are described. Two were found in urinary tract infections and the third in a respiratory infection. They were shown by typing methods to be distinct strains.
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The yeast retrotransposon Ty1 has been used to insert multiple copies of heterologous genes into the genome of Saccharomyces cerevisiae. Amplification using a GAL1-regulated Ty1 element carrying a 4.6 kilobase pair expression cassette (Escherichia coli lacZ structural gene under the control of the yeast CUP1 promoter, and the bacterial neo gene) was compared with that of a GAL1-regulated Ty1 element carrying only the neo gene. Mobilization of Ty1 was induced from a chromosomal element and a 2 mu-plasmid-based element; similar results were obtained for both locations. The two marked Ty1 cassettes were successfully integrated into the genomes of three different S. cerevisiae strains. Efficiencies were found to vary significantly between strains. The size of the inserted cassette was also important; the efficiency for the CUP1p-lacZ-neo cassette was much lower than that for the neo cassette in the same host. All amplified copies were found to be quite stable with or without expression for at least 50 generation in nonselective medium; moreover, there were no significant effects on the growth of the cells. After integration, beta-galactosidase specific activity from the lacZ construct in the three hosts was found to correlate well with the copy number of the CUP1p-lacZ expression cassette amplified by the Ty1 retrotransposon.
A novel delta-integration vector was developed to allow the sequential insertion of multiple cloned genes in the yeast Saccharomyces cerevisiae. To allow repetitive integrations, the reusable URA3 Blaster selection cassette was employed; the insertions (of CUP1p-lacZ in this study) were selected using the URA3 marker which was subsequently "popped" out by recombination between flanking direct repeats. Transformants contained only one new integrated copy after the loss of the URA3 marker, and subsequent transformations were effective for the sequential insertion of a series of genes (one at a time) into dispersed chromosomal delta sequences. The structural stability of the integrations was location-dependent (ranging from 75% to 100% after 50 generations in complex medium with or without gene expression), and the integrations (at least up to five) had no significant effects on the growth of the cells. In addition, beta-galactosidase specific activity levels varied linearly with integrated copy number. The repetitive, regulated nature of integration with this vector is not possible with traditional delta-integration or other homologous recombination methods, and is promising for fine-tuning cloned gene copy number and for the insertion of metabolic pathway genes.
BACKGROUND: Although primary care physicians are increasingly interested in adopting electronic medical record (EMR) systems, few use such systems in practice. This study explores the organizational impact of an EMR system on community-based practices that have overcome the initial barriers and are experienced EMR users. METHODS: Five primary care practices that are members of a national research network participated in this study. Using qualitative methods, including semistructured interviews and observations, we assessed the impact of an EMR system on the work lives of various user groups. RESULTS: Physicians and staff indicated that the EMR system has changed not only how they manage patient records but also how they communicate with each other, provide patient care services, and perform job responsibilities. The EMR is also perceived by its users to have an impact on practice costs. Although in most practices physicians and staff were unaware of actual expenses and cost savings associated with the EMR, those in practices that have eliminated duplicate paper-based systems believe they have realized cost savings. CONCLUSIONS: Several important themes emerged. The organizational context in which the system is implemented is important. Effective leadership, the presence of a system champion, availability of technical training and support, and adequate resources are essential elements to the success of the EMR.