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Biomedical subjects

J J Young

Publications and source records attributed to J J Young.

At least 19 recordsLinked to original sources
PubMed2006

Decision threshold adjustment in class prediction.

Standard classification algorithms are generally designed to maximize the number of correct predictions (concordance). The criterion of maximizing the concordance may not be appropriate in certain applications. In practice, some applications may emphasize high sensitivity (e.g., clinical diagnostic tests) and others may emphasize high specificity (e.g., epidemiology screening studies). This paper considers effects of the decision threshold on sensitivity, specificity, and concordance for four classification methods: logistic regression, classification tree, Fisher's linear discriminant analysis, and a weighted k-nearest neighbor. We investigated the use of decision threshold adjustment to improve performance of either sensitivity or specificity of a classifier under specific conditions. We conducted a Monte Carlo simulation showing that as the decision threshold increases, the sensitivity decreases and the specificity increases; but, the concordance values in an interval around the maximum concordance are similar. For specified sensitivity and specificity levels, an optimal decision threshold might be determined in an interval around the maximum concordance that meets the specified requirement. Three example data sets were analyzed for illustrations.

Algorithms↗
PubMed2005

Quantitative density profiling with pure phase encoding and a dedicated 1D gradient.

A new centric scan imaging methodology for density profiling of materials with short transverse relaxation times is presented. This method is shown to be more robust than our previously reported centric scan pure phase encode methodologies. The method is particularly well suited to density imaging of low gyro-magnetic ratio non-proton nuclei through the use of a novel dedicated one-dimensional magnetic field gradient coil. The design and construction of this multi-layer, water cooled, gradient coil is presented. Although of large diameter (7.62 cm) to maximize sample cross section, the gradient coil has an efficiency of several times that offered by conventional designs (6 mT/m/A). The application of these ideas is illustrated with high resolution density-weighted proton (1H) images of hazelnut oil penetration into chocolate, and lithium ion (7Li) penetration into cement paste. The methods described in this paper provide a straightforward and reliable means for imaging a class of samples that, until now, have been very difficult to image.

Cacao↗
PubMed2001

Differential effects of citrate versus PPACK anticoagulation on measured platelet inhibition by abciximab, eptifibatide and tirofiban.

BACKGROUND: High levels of glycoprotein (GP) IIb/IIIa receptor inhibition are required to prevent arterial thrombosis following percutaneous coronary intervention. Ex-vivo turbidometric platelet aggregation in citrate anticoagulated blood samples has been the primary method previously utilized to derive dose regimens for administering platelet GP IIb/IIIa inhibitors. Enhanced GP IIb/IIIa binding and inhibition of platelet aggregation for eptifibatide secondary to citrate induced reduction of ionized plasma calcium concentrations has been reported. METHODS/RESULTS: We evaluated the differential effects of citrate versus PPACK anticoagulation on turbidometric platelet inhibition in normal volunteers by eptifibatide, tirofiban or abciximab. The decrease in ionized calcium afforded by citrate was associated with enhanced in vitro platelet inhibition for all three GP IIb/IIIa inhibitors, including abciximab. The magnitude of citrate effect was greatest for eptifibatide. Both tirofiban and abciximab have similar citrate calcium chelation associated enhancement of measured platelet inhibition. CONCLUSION: Accurate assessment and comparison of platelet inhibition by GP IIb/IIIa inhibitors may require avoidance of calcium chelating anticoagulants.

Abciximab↗
PubMed2000

Abciximab: cost-effective survival advantage in clinical trials and clinical practice.

Adjunctive blockade of the platelet glycoprotein (GP) IIb/IIIa receptor during either percutaneous coronary intervention (PCI) or for patients who present with non-ST segment elevation acute coronary syndromes has demonstrated efficacy in reducing platelet-mediated adverse cardiovascular ischemic events. The three currently available agents (abciximab, eptifibatide, tirofiban) differ markedly in pharmacodynamic and pharmacokinetic profiles, receptor affinity, and cost. Although pharmacoeconomic substudies are available from placebo-controlled randomized trials of platelet GPIIb/IIIa blockade during PCI, "real-world" cost-effectiveness data from high-volume practice are lacking. Therefore, in-hospital and late (6-month) clinical outcomes and cumulative cost/charge data were analyzed on 1472 consecutive PCI procedures (70% received abciximab) performed by high-volume operators at a single institution.(1) Data were adjusted for lack of randomized treatment allocation with the use of a propensity scoring technique. Adjunctive abciximab therapy for PCI was associated with a significant (3.4%) reduction in mortality to 6 months. Based on the economic cost-effectiveness concept of cost per life year gained relative to standard therapy,(2,3) abciximab provided a cost-effective survival advantage in high-volume interventional practice that compares very favorably with currently accepted standards. Clinical and procedural demographics associated with increased cost-effectiveness include multivessel coronary intervention, stent deployment, recent (<1 week) myocardial infarction (MI), and impaired left-ventricular (LV) function.

Abciximab↗
PubMed2000

Low-molecular-weight heparin therapy in percutaneous coronary intervention: the NICE 1 and NICE 4 trials. National Investigators Collaborating on Enoxaparin Investigators.

Early coronary intervention in patients with non-ST segment elevation acute coronary syndromes (ACS) may be facilitated by adjunctive pharmacotherapies. Concomitant therapies such as low-molecular-weight heparins and platelet glycoprotein (GP) IIb/IIIa receptor blockade offer advantages in safety and efficacy during coronary intervention. Data from randomized clinical trials support the administration of both enoxaparin and platelet GP IIb/IIIa blockade to patients who present with non-ST segment elevation ACS. Enoxaparin, with its proven efficacy, predictability of action, and ease of administration, has been shown to be superior to unfractionated heparin in preventing major coronary events. Abciximab administration during percutaneous coronary intervention (PCI) reduces the incidence of ischemic adverse outcomes and appears to improve survival in long-term follow-up. The preliminary experience with combining these two therapies during PCI in the NICE 4 trial demonstrates a low incidence of minor/major bleeding and transfusion, and infrequent major cardiac events to 30 days follow-up. Algorithms for the use of these newer adjunctive pharmacotherapies in the care of patients presenting to the cardiac catheterization laboratory are presented.

Abciximab↗
PubMed1997

The effect of food on the pharmacokinetics of the bicalutamide ('Casodex') enantiomers.

'Casodex' (bicalutamide) is an orally active, non-steroidal, pure antiandrogen; it is a racemate with antiandrogenic activity residing predominantly in the (R)-enantiomer. Healthy male volunteers (n = 15) were administered single oral doses of bicalutamide (50 mg) after food and after fasting as part of a three-treatment, three-period, randomized cross-over study, with a 9 week washout. After fasting, plasma concentrations of (R)-bicalutamide were much higher than those of (S)-bicalutamide; the mean (R)-enantiomer Cmax (734 ng mL-1) was about nine times higher than the (S)-enantiomer value (84 ng mL-1). The corresponding tmax values were 19 and 3 h for (R)- and (S)-bicalutamide, respectively. Elimination of (R)-bicalutamide from plasma was monoexponential and slow (t1/2 = 5.8 d). Elimination of (S)-bicalutamide was biphasic in some volunteers but monophasic in others (terminal t1/2 =1.2 d; n = 11). There was no significant effect of food on AUC, tmax, or t1/2 data for either enantiomer. The observed slightly higher values of Cmax for (R)-bicalutamide (14%) and (S)-bicalutamide (19%), when dosing with food, achieved statistical significance. However, differences of this magnitude are unlikely to to be of any clinical relevance. These data indicate that 'Casodex' can be taken without reference to meal times; this may be of particular relevance for its indication in a disease of the elderly.

Administration, Oral↗
PubMed1994

Three-dimensional structure in solution of griseoviridin, a group A antibiotic.

The solution conformation of griseoviridin, a broad spectrum antibiotic, has been determined by 1H-NMR in deuterated dimethylsulfoxide. The structural determination is based on experimental data of NOE constraints Five structures were obtained from restrained molecular dynamics calculations, by imposing (the condition for) a minimum violation of distance constraints. These structures satisfy well the experimental restraints, with small values of NOE violation and total energies. On comparison with its crystal structure, a good agreement is noted with a backbone root-mean-square deviation value of 0.084 nm. However, a small variation between the structures is observed at the aminodecanoic acid part of the molecule.

Anti-Bacterial Agents↗
PubMed1994

FL-120A-D', new products related to kinamycin from Streptomyces chattanoogensis subsp. taitungensis subsp. nov. II. Isolation and structure determination.

Six new kinamycin antibiotics have been isolated from the culture filtrate of Streptomyces chattanoogensis. The structures of six related components were determined employing 1D and 2D NMR spectroscopy and mass spectrometry. These structures represent the first reported epoxide kinamycin (2, 3) and propionyl derivative of kinamycin (5), and new isobutyryl derivatives of kinamycin (1, 4, 6).

Anti-Bacterial Agents↗
PubMed1994

Solution conformation of enopeptin A, a depsipeptide antibiotic, using 2D NMR and restrained molecular dynamics studies.

Studies on the solution conformation of the cyclic depsipeptide antibiotic enopeptin A have been carried out using 2D NMR and molecular modelling techniques. The proton resonances of the antibiotic in DMSO-d6 have been assigned by the use of TOCSY and ROESY experiments. The interproton distance information obtained from the ROESY experiments have been used as the basis for elucidating the probable structures in solution. The restrained molecular dynamics technique was applied to calculate the structures in solution, and six resultant structures with fewer distance constraint violations were obtained that satisfy the experimental restraints very well. The conformation of the cyclic moiety of the molecules is well defined whereas the aliphatic chain segment is disordered.

Amino Acid Sequence↗
PubMed1993

Sustained release of salmon calcitonin in vivo from lactide: glycolide copolymer depots.

Studies were carried out to determine whether monolithic depot formulations, prepared using lactide:glycolide copolymers, could be used to administer salmon calcitonin (sCT) to rats in vivo. Formulations containing 2, 5, or 10% (w/w) sCT were administered subcutaneously to female Wistar strain rats. Release of sCT was determined by measurement of peptide in plasma using a specific radioimmunoassay and by measurement of residual sCT in the depots after recovery at postmortem. Plasma calcium concentrations and cumulative weight gain of the animals were used to measure pharmacological effects of the released sCT. Release of sCT from the depots was controlled by the copolymer and was sustained for periods up to 10 days. However, the release of sCT from the depots did not significantly alter plasma calcium concentrations, and effects on cumulative weight gain were small and transient. Peptide loading of the formulations was shown to modify sCT release. Maximal release of sCT from depots containing 10% peptide occurred over a 7 to 14-day period postadministration, with 5% sCT release occurred between days 11 and 14, and with 2% sCT, the period of maximal release was between days 11 and 18. Release of peptide from the depots was essentially complete by 21 days postadministration irrespective of the peptide loading. These data suggest that lactide:glycolide copolymer depots may have application for the convenient clinical administration of sCT in metabolic bone diseases.

Animals↗