Search PubMed⌕ Search

Biomedical subjects

D B Hall

Publications and source records attributed to D B Hall.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacokinetic parameters of nevirapine and efavirenz in relation to antiretroviral efficacy.

Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (Cmin) and total drug exposure over 24 hr (AUC24) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the double nonnucleoside study (2NN), which compared the efficacy of NVP and/or EFV together with stavudine and lamivudine. The objective was to find cutoff values of the Cmin and AUC24 below which the risk of virologic failure increased. The relation between Cmin and AUC24 with virologic failure (never a plasma viral load [pVL] < 50 copies/ml or a rebound to two consecutive pVL > 50 copies/ml) was analyzed with proportional hazard analyses. Data were censored at end of study or change of allocated treatment. The risk of virologic failure with NVP (n = 511) started to increase at a Cmin < 3.1 mg/L (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.89-1.97), but there was no cutoff value below which a statistically significant increased risk occurred. Neither was such a cutoff point identified for the AUC24. The risk of virologic failure with EFV (n = 312) was significantly increased at a Cmin < 1.1 mg/L (HR, 1.95; 95% CI, 1.08-3.54) and an AUC24 < 40 mg x hr x L1 (HR, 1.95; 95% CI, 1.07-3.54). Both cutoff values represent the median values for adherent patients. These associations were driven by patients from Thailand. Adjusting for geographical region made the association between Cmin and AUC24 with virologic failure statistically nonsignificant. The sensitivity of the Cmin values was too low (29% for NVP, 64% for EFV) to be an adequate predictor for virologic failure. We conclude that identifying the Cmin value for the sole purpose of predicting virologic failure in patients who report to be adherent to NVP or EFV is questionable because of the absence of a concentration-response relation (NVP) or the low sensitivity for such a cutoff value (NVP and EFV).

Adult↗
PubMed2006

Plasma lipid concentrations after 1.5 years of exposure to nevirapine or efavirenz together with stavudine and lamivudine.

OBJECTIVES: To assess long-term changes in lipids and lipoproteins concentrations associated with exposure to non-nucleoside reverse transcriptase inhibitors. METHODS: Long-term analysis of plasma lipid concentrations was performed in patients starting first-line antiretroviral therapy with stavudine (d4T) and lamivudine, and either nevirapine or efavirenz. RESULTS: Concentrations of total cholesterol, low-density lipoprotein cholesterol and triglycerides continued to increase, while high-density lipoprotein cholesterol showed a slight decrease compared with earlier reported increases after 48 weeks. CONCLUSIONS: Changes in body fat distribution expected to occur with continued exposure to d4T could offer a potential explanation for these findings.

Alkynes↗
PubMed2002

Confinement and processing effects on glass transition temperature and physical aging in ultrathin polymer films: novel fluorescence measurements.

Fluorescence intensity measurements of chromophore-doped or -labeled polymers have been used for the first time to determine the effects of decreasing film thickness on glass transition temperature, T(g), the relative strength of the glass transition, and the relative rate of physical aging below T(g) in supported, ultrathin polymer films. The temperature dependence of fluorescence intensity measured in the glassy state of thin and ultrathin films of pyrene-doped polystyrene (PS), poly(isobutyl methacrylate) (PiBMA), and poly(2-vinylpyridine) (P2VP) differs from that in the rubbery state with a transition at T(g). Positive deviations from bulk T(g) are observed in ultrathin PiBMA and P2VP films on silica substrates while substantial negative deviations from bulk T(g) are observed in ultrathin PS films on silica substrates. The relative difference in the temperature dependences of fluorescence intensity in the rubbery and glassy states is usually reduced with decreasing film thickness, indicating that the strength of the glass transition is reduced in thinner films. The temperature dependence of fluorescence intensity also provides useful information on effects of processing history as well as on the degree of polymer-substrate interaction. In addition, when used as a polymer label, a mobility-sensitive rotor chromophore is demonstrated to be useful in measuring relative rates of physical aging in films as thin as 10 nm.

Journal Article↗
PubMed2001

Application technique and irrigation method affect imidacloprid control of silverleaf whiteflies (Homoptera: Aleyrodidae) on poinsettias.

Subirrigation systems are increasingly used to water and fertilize greenhouse crops. They also appear to be well suited for the application of systemic pesticides. We conducted two studies to look at interactive effects ofimidacloprid application technique and irrigation method on plant uptake of imidacloprid and whitefly control. Drench applications of imidacloprid resulted in much higher concentrations in the leaves than applications to the bottom of pots after 14 d. However, imidacloprid efficacy in subirrigated plants was better if the imidacloprid was applied to the bottom of the pot than when an equal amount was applied as a drench. In drip-irrigated plants, imidacloprid efficacy was greater after a drench than after an application to the bottom of the pots. A second study showed that drench applications to drip-irrigated plants result in high imidacloprid concentrations in the bottom of the canopy, whereas bottom applications to subirrigated plants result in a more even distribution of imidacloprid throughout the plant. Surprisingly, the high leaf imidacloprid concentrations in the bottom layer of drip-irrigated plants did not result in improved whitefly control. Imidacloprid efficacy was better in subirrigated, bottom-treated plants than in drip-irrigated, drenched plants. Overall, results from these studies indicate that imidacloprid is very effective when applied to the bottom of subirrigated pots.

Agriculture↗
PubMed2000

Zero-inflated Poisson and binomial regression with random effects: a case study.

In a 1992 Technometrics paper, Lambert (1992, 34, 1-14) described zero-inflated Poisson (ZIP) regression, a class of models for count data with excess zeros. In a ZIP model, a count response variable is assumed to be distributed as a mixture of a Poisson(lambda) distribution and a distribution with point mass of one at zero, with mixing probability p. Both p and lambda are allowed to depend on covariates through canonical link generalized linear models. In this paper, we adapt Lambert's methodology to an upper bounded count situation, thereby obtaining a zero-inflated binomial (ZIB) model. In addition, we add to the flexibility of these fixed effects models by incorporating random effects so that, e.g., the within-subject correlation and between-subject heterogeneity typical of repeated measures data can be accommodated. We motivate, develop, and illustrate the methods described here with an example from horticulture, where both upper bounded count (binomial-type) and unbounded count (Poisson-type) data with excess zeros were collected in a repeated measures designed experiment.

Animals↗
PubMed2000

Imidacloprid applications by subirrigation for control of silverleaf whitefly (Homoptera: Aleyrodidae) on poinsettia.

The objective of this study was to determine whether silverleaf whiteflies, Bemisia argentifolii Bellows & Perring, on poinsettia, Euphorbia pulcherrima Willdenow ex Klotsch, can be controlled with imidacloprid applied by subirrigation. Different amounts of imidacloprid uptake by the growing medium were obtained by not watering the subirrigated plants for 0, 1, 2, or 4 d before the imidacloprid application. These treatments resulted in absorption of 12-175 ml of imidacloprid solution by the growing medium. These treatments were compared with untreated control plants and plants that were treated with a standard drench application (100 ml) to the top of the growing medium. All imidacloprid treatments resulted in a significant decrease in both the survival of adult whiteflies and number of immature whiteflies on the plants. Subirrigation treatments resulted in better control of adult and immature whiteflies than drench application. Withholding water for 2 or 4 d before the imidacloprid application by subirrigation improved control of immature whiteflies. This indicates that the application of imidacloprid to poinsettia by subirrigation is a practical and efficient method to control silverleaf whiteflies.

Animals↗
PubMed1999

Long-range oxidative damage to DNA: effects of distance and sequence.

INTRODUCTION: Oxidative damage to DNA in vivo can lead to mutations and cancer. DNA damage and repair studies have not yet revealed whether permanent oxidative lesions are generated by charges migrating over long distances. Both photoexcited *Rh(III) and ground-state Ru(III) intercalators were previously shown to oxidize guanine bases from a remote site in oligonucleotide duplexes by DNA-mediated electron transfer. Here we examine much longer charge-transport distances and explore the sensitivity of the reaction to intervening sequences. RESULTS: Oxidative damage was examined in a series of DNA duplexes containing a pendant intercalating photooxidant. These studies revealed a shallow dependence on distance and no dependence on the phasing orientation of the oxidant relative to the site of damage, 5'-GG-3'. The intervening DNA sequence has a significant effect on the yield of guanine oxidation, however. Oxidation through multiple 5'-TA-3' steps is substantially diminished compared to through other base steps. We observed intraduplex guanine oxidation by tethered *Rh(III) and Ru(III) over a distance of 200 A. The distribution of oxidized guanine varied as a function of temperature between 5 and 35 degrees C, with an increase in the proportion of long-range damage (> 100 A) occurring at higher temperatures. CONCLUSIONS: Guanines are oxidized as a result of DNA-mediated charge transport over significant distances (e.g. 200 A). Although long-range charge transfer is dependent on distance, it appears to be modulated by intervening sequence and sequence-dependent dynamics. These discoveries hold important implications with respect to DNA damage in vivo.

DNA↗
PubMed1999

Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1.

Nevirapine and indinavir have the potential of affecting the pharmacokinetics of each other. In a prospective trial, 24 human immunodeficiency virus (HIV)-infected subjects on stable nucleoside or no therapy were treated with 800 mg of indinavir every 8 h. After 7 days, 200 mg of nevirapine a day was added for 14 days and then increased to 200 mg twice a day. At day 7 (before nevirapine), there was a sevenfold difference among the subjects in indinavir area under the curve (AUC), and there was a significant correlation between indinavir AUC (r2=0.378, P=.019), minimum plasma concentration (Cmin; r2=0.359, P=.023), maximum plasma concentration (Cmax; r2=0.340, P=.028), and plasma HIV RNA decline. Nevirapine significantly reduced median indinavir Cmin (47.5%) and AUC (27.4%) and, to a lesser extent, Cmax (11%). Plasma HIV RNA values were </=20 copies/mL in 10 of 17 (58.8%) subjects at 58 weeks or last visit. These data suggest that indinavir dosing should be dependent on drug exposure and not on cotherapy with nevirapine.

Adolescent↗
PubMed1998

Long-range and short-range oxidative damage to DNA: photoinduced damage to guanines in ethidium-DNA assemblies.

Short-range and long-range photoreactions between ethidium and DNA have been characterized. While no DNA reaction is observed upon excitation into the visible absorption band of ethidium, higher-energy irradiation (313-340 nm) leads both to direct strand cleavage at the 5'-G of 5'-GG-3' doublets and to piperidine-sensitive lesions at guanine. This reactivity is not consistent with oxidation of guanine by either electron transfer or singlet oxygen as shown by comparison with reactions of a rhodium intercalator and methylene blue, respectively. By covalently tethering ethidium to one end of a DNA duplex, we demonstrate the presence of two distinct reactions, one short-range and the other long-range. The short-range reaction involves a covalent modification of guanine by ethidium, based upon HPLC analysis of the nucleoside products and studies with ethidium derivatives. The long-range reaction is entirely consistent with oxidation of guanine by DNA-mediated electron transfer. The yield of this electron-transfer reaction is not attenuated with distance; equal yields of guanine damage are observed at a proximal (17 A Et-GG separation) and distal (44 A Et-GG separation) site. These results are quite similar to those previously observed with a covalently tethered rhodium photooxidant and underscore the unique ability of the DNA base stack to facilitate long-range electron transfer so as to effect oxidative damage from a distance.

Alkylation↗
PubMed1998

Induction-maintenance antiretroviral therapy: proof of concept.

OBJECTIVE: To investigate the concept of aggressive initial combination therapy followed by reduction to a less demanding maintenance regimen with respect to its potential for sustaining viral suppression. DESIGN: Durable viral suppression to < 20 HIV RNA copies/ml plasma was achieved with zidovudine-nevirapine-didanosine (ZDV-NVP-ddl) therapy. Potential for sustained antiviral response was explored for patients who began with ZDV-NVP-ddl and subsequently interrupted ddl. METHODS: Antiretroviral-naive patients were treated with ZDV-NVP, ZDV-ddl, or ZDV-NVP-ddl. Viral load was measured with the Amplicor assay (limit of quantification 400 copies/ml) and by the Ultra Direct assay (limit of quantification 20 copies/ml) when the Amplicor result was < 500 copies/ml. Treatment adherence for each drug was recorded, including all dose adjustments. RESULTS: Five patients who had begun treatment with ZDV-NVP-ddl discontinued ddl for at least 6 weeks after achieving viral load levels below detection. All were documented to have sustained their viral load at < 20 copies/ml during the ddl interruption. Two patients permanently discontinued ddl, both with sustained viral load below detection for more than 1 year while treated with ZDV NVP. In contrast, no patient initially receiving ZDV-NVP was able to maintain viral load below detection for sustained periods; none had viral load below detection after week 12 of treatment. CONCLUSIONS: After induction with ZDV-NVP-ddl, patients were able to sustain viral suppression with a regimen (ZDV NVP) that was only transiently effective as initial therapy. There was no evidence of virologic escape, even with the most sensitive measure of plasma viral load.

Anti-HIV Agents↗
PubMed1996

Oxidative DNA damage through long-range electron transfer.

The possibility has been considered for almost forty years that the DNA double helix, which contains a pi-stacked array of heterocyclic base pairs, could be a suitable medium for the migration of charge over long molecular distances. This notion of high charge mobility is a critical consideration with respect to DNA damage. We have previously found that the DNA double helix can serve as a molecular bridge for photo-induced electron transfer between metallointercalators, with fast rates (> or = 10(10)s-1) and with quenching over a long distance (>40 A). Here we use a metallointercalator to introduce a photoexcited hole into the DNA pi-stack at a specific site in order to evaluate oxidative damage to DNA from a distance. Oligomeric DNA duplexes were prepared with a rhodium intercalator covalently attached to one end and separated spatially from 5'-GG-3' doublet sites of oxidation. Rhodium-induced photo-oxidation occurs specifically at the 5'-G in the 5'-GG-3' doublets and is observed up to 37 A away from the site of rhodium intercalation. We find that the yield of oxidative damage depends sensitively upon oxidation potential and pi-stacking, but not on distance. These results demonstrate directly that oxidative damage to DNA may be promoted from a remote site as a result of hole migration through the DNA pi-stack.

Base Sequence↗
PubMed1996

A computer program for regression analysis of ordered categorical repeated measurements.

RMORD is an easy-to-use FORTRAN program for the analysis of clustered ordinal data using the method of Stram, Wei, and Ware. This method constitutes an extension of the proportional-odds model to the situation in which groups of responses are correlated. At each measurement occasion, a proportional-odds regression model is fit to the data by maximizing the occasion-specific likelihood function. The joint asymptotic distribution of the occasion-specific regression parameter estimators is obtained along with a consistent estimator of their asymptotic covariance matrix. RMORD may be used when ordinal measurements are obtained at a common set of observation times for multiple subjects or clusters. Both missing data and covariates which vary within clusters can be accommodated. The program can be run on microcomputers, workstations, and mainframe computers. Two examples illustrating the usage and features of RMORD are provided.

Age Distribution↗
PubMed1996

Sodium and potassium currents of type I spiral ganglion cells from rat.

Ion channel activity of acutely dissociated type I spiral ganglion cells isolated from rats was investigated using the whole-cell variation of the patch clamp technique. Tetrodotoxin-sensitive sodium current and tetraethylammonium-sensitive potassium current were recorded. With a holding potential of -80 mV, peak sodium currents were generated by depolarizations to membrane potentials more positive than -50 mV. Potassium currents were elicited at membrane potentials more positive than -40 mV. Some cells which did not exhibit sodium current exhibited delayed rectifier potassium currents. Steady-state sodium channel inactivation curve yielded a slope of 12 mV and a half-inactivated potential of -83 mV. Recovery from inactivation of the sodium channel proceeded with a fast and slow time course; recovery began as early as 0.8 ms and proceeded with a time constant of 7.5 ms. It is concluded that type I spiral ganglion cells are endowed with sodium and potassium channels which are responsible for generation and propagation of auditory nerve action potentials.

Action Potentials↗
PubMed1995

Auditory cortex neurons: primary culture and ion channel activity in rat.

We have developed a primary dissociated cell culture of the fetal (E17) and post-natal (P0-P10) rat auditory cortex. Pyramidal and non-pyramidal cells had a mean cross-sectional diameter of 12.73 +/- 1.80 microns (mean +/- S.D., n = 25) and 17.58 +/- 1.67 microns (mean +/- S.D., n = 10), respectively, measured at 6 days in culture. These cells were viable for as long as 18-21 days. They expressed voltage-gated sodium and potassium channel currents as early as one day in culture, and at various phases in cell culture. Sodium current, activated at membrane potentials more positive than -60 mV, displayed fast activation and inactivation kinetics. Fifty percent inactivation of sodium channels occurred at a pre-pulse potential of -63 mV. Delayed rectifier potassium channels were activated at potentials positive to -40 mV. Large hyperpolarizing constant current pulses elicited anode break action potentials, and large depolarizing constant current pulses exhibited rectification indicative of the delayed rectifying potassium channel activity.

Animals↗