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Biomedical subjects

L G Miller

Publications and source records attributed to L G Miller.

At least 37 records · Page 2Linked to original sources
PubMed1997

Sustained release of acetaminophen from heterogeneous matrix tablets: influence of polymer ratio, polymer loading, and co-active on drug release.

The aim of this research was to investigate the effect of pseudoephedrine (PE), polymer ratio, and polymer loading on the release of acetaminophen (APAP) from hydroxypropyl methyl cellulose (HPMC)/polyvinylpyrrolidone (PVP) matrices. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and PVP were compressed into tablets at varying compression forces ranging from 2000 to 6000 Ib. In vitro drug release from the matrix tablets was determined and the results correlated with those of tablet water uptake and erosion studies. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP (P < 0.05, F = 3.10). Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45, and at high total polymer loading (> or = 9.6%). Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.45. At pH 1.16, a decline in the percentage of APAP released occurred after 18 hours. This was due to the hydrolysis of APAP to p-aminophenol. The drug dissolution data showed good fit to the Korsmeyer and Peppas model, and the values of the release exponents ranged from 0.20 to 0.62, indicating a complex drug release pattern. Tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation controlled mechanism. Overall, the results of this study indicated that PE, as a co-active in the formulation, modified the matrix, and hence retarded APAP release.

Acetaminophen↗
PubMed1997

Meningitis in older patients: how to diagnose and treat a deadly infection.

Studies of bacterial meningitis have documented a peak of incidence among persons age 60 and older. The most common bacterial pathogens in these patients differ from those seen in children. Presentation of meningitis in older patients may be atypical; fever is not a consistent finding, and nonspecific symptoms such as confusion are often seen. Nuchal rigidity is not as sensitive nor as specific a sign as in younger patients. Definitive diagnosis relies on interpretation of CSF studies. Ampicillin plus a third-generation cephalosporin should be administered for community-acquired meningitis until Gram's stain and culture results return. Cases of S pneumoniae meningitis may require varying strategies, based upon the degree of penicillin resistance.

Aged↗
PubMed1996

Pulsed-field gel electrophoresis and ribotype profiles of clinical and environmental Vibrio vulnificus isolates.

Vibrio vulnificus belongs to the autochthonous bacterial flora of warm estuarine waters. It can cause life-threatening extraintestinal disease in persons who have underlying illness and who consume raw shellfish or contact wounds with estuarine water. Currently, very little is known about genetic diversity within this species. In this report, we describe high-level variation in restriction fragment length polymorphism profiles among 53 clinical and 78 environmental isolates, as determined by pulsed-field gel electrophoresis. In contrast, ribotype profiles showed greater similarity. When combined ribotype profiles of clinical and environmental isolates were analyzed, four predominant clusters were observed. Interestingly, a low number (16%) of clinical isolates were found in cluster C, compared with clusters A, B, and D (range, 50 to 83%). In addition, 83% of all Hawaiian isolates were located in a single cluster, indicating a possible relationship between geography and genotype. We also report that spontaneous translucent colonial morphotypes were distinct by both restriction fragment length polymorphism and biochemical profiles, compared with opaque parent strains.

Bacterial Typing Techniques↗
PubMed1995

Pregnenolone sulfate potentiation of NMDA-mediated increases in intracellular calcium in cultured chick cortical neurons.

Pregnenolone sulfate (PS) has been reported to selectively augment glutamate-induced depolarizations mediated by the NMDA subtype of the glutamate receptor. The present study examines the ability of this neuroactive steroid to potentiate NMDA-mediated increases in intracellular calcium in cultured chick cortical neurons using the fluorescent dye Fura2. PS, in the absence of NMDA and glycine, significantly elevated intracellular calcium at 250 and 500 microM. This increase in free calcium was significantly attenuated at 250 microM PS by the prior addition of 50 microM CNQX, 10 microM dizocilpine or 1 microM nimodipine. NMDA and glycine, when added to the cells in saturating concentrations of 500 and 50 microM, respectively, consistently increased intracellular free calcium over baseline levels. In the presence of NMDA and glycine, both 50 and 100 microM PS produced a further significant rise in intracellular free calcium. The prior addition of CNQX, dizocilpine or both compounds together significantly inhibited this elevation in free calcium. The application of the endogenous polyamine spermine (250 microM) significantly potentiated the response of chick cortical neuronal cells to NMDA and glycine. PS, in the presence of NMDA, glycine and spermine, produced a further increase in intracellular free calcium at concentrations of 50 and 100 microM. The prior application of CNQX, dizocilpine or both compounds together significantly attenuated this rise in free calcium. These data confirm that PS is a positive allosteric modulator of the NMDA receptor and provide evidence that this neurosteroid does not interact with the polyamine modulatory site.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Prenatal lorazepam exposure: 4. Persistent alterations in pentylenetetrazole-induced seizure threshold and GABA-dependent chloride uptake after prenatal lorazepam exposure.

Prenatal benzodiazepine exposure is associated with behavioral and neurochemical alterations in the early postnatal period. To determine the persistence of these effects, we evaluated pentylenetetrazole-induced seizure threshold and GABA-dependent chloride uptake in mice at 6 and 12 months of age after prenatal lorazepam exposure. Seizure threshhold was reduced after acute lorazepam pretreatment in mice exposed to lorazepam prenatally, compared to control groups, at 6 and 12 months of age. Maximal GABA-dependent chloride uptake was also reduced in exposed mice at 6 and 12 months of age. These data indicate that behavioral and neurochemical alterations persist well into maturity after prenatal lorazepam exposure.

Animals↗
PubMed1995

Methylmercury oxidative degradation potentials in contaminated and pristine sediments of the carson river, nevada.

Sediments from mercury-contaminated and uncontaminated reaches of the Carson River, Nevada, were assayed for sulfate reduction, methanogenesis, denitrification, and monomethylmercury (MeHg) degradation. Demethylation of [(sup14)C]MeHg was detected at all sites as indicated by the formation of (sup14)CO(inf2) and (sup14)CH(inf4). Oxidative demethylation was indicated by the formation of (sup14)CO(inf2) and was present at significant levels in all samples. Oxidized/reduced demethylation product ratios (i.e., (sup14)CO(inf2)/(sup14)CH(inf4) ratios) generally ranged from 4.0 in surface layers to as low as 0.5 at depth. Production of (sup14)CO(inf2) was most pronounced at sediment surfaces which were zones of active denitrification and sulfate reduction but was also significant within zones of methanogenesis. In a core taken from an uncontaminated site having a high proportion of oxidized, coarse-grain sediments, sulfate reduction and methanogenic activity levels were very low and (sup14)CO(inf2) accounted for 98% of the product formed from [(sup14)C]MeHg. There was no apparent relationship between the degree of mercury contamination of the sediments and the occurrence of oxidative demethylation. However, sediments from Fort Churchill, the most contaminated site, were most active in terms of demethylation potentials. Inhibition of sulfate reduction with molybdate resulted in significantly depressed oxidized/reduced demethylation product ratios, but overall demethylation rates of inhibited and uninhibited samples were comparable. Addition of sulfate to sediment slurries stimulated production of (sup14)CO(inf2) from [(sup14)C]MeHg, while 2-bromoethanesulfonic acid blocked production of (sup14)CH(inf4). These results reveal the importance of sulfate-reducing and methanogenic bacteria in oxidative demethylation of MeHg in anoxic environments.

Journal Article↗
PubMed1995

Provider profiling: advancing to episodes of care.

Judging by the interest expressed by managed care organizations, provider profiling has arrived. Surveys indicate that most organizations have adopted, or plan to adopt in the near future, a means to describe provider practice patterns. A further vote of confidence came from providers: In 1994, the American College of Physicians, the largest national specialty organization, issued a position paper supporting provider profiling and questioning the value of other approaches to utilization management, such as preauthorization of individual services. Also, an article and an editorial in the New England Journal of Medicine cautiously supported the concept of profiling. Provider profiling has great promise as a means to promote cost-effective care without the limitations of case-by-case preauthorization. The combination of a sophisticated episode of care methodology and a set of validated practice benchmarks offers the opportunity to perform true clinical profiling and to supply providers with data to review and alter practice patterns.

Cost-Benefit Analysis↗
PubMed1994

Interleukin-1 modulates GABAergic and glutamatergic function in brain.

Interleukin-1 is a polypeptide cytokine involved in the acute-phase response. We examined the effects of IL-1 on the major inhibitory and excitatory neurotransmitter systems in brain mediated by GABA and glutamate, respectively. IL-1 enhanced the effects of GABA as determined by GABA-dependent chloride uptake at 1 and 10 ng/ml in cortical synaptoneurosomes. This effect was attenuated by pretreatment with the IL-1 receptor antagonist. Neither IL-6 nor TNF was effective in this system. IL-1 decreased the effect of NMDA and glycine on intracellular calcium concentrations in cultured chick cortical neurons in both the presence and absence of the endogenous polyamine spermine. This effect was attenuated by pretreatment with the AMPA/kainate antagonist CNQX. These data indicate that IL-1 modulates both inhibitory and excitatory neurotransmitter function in brain.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Polyamine potentiation and inhibition of NMDA-mediated increases of intracellular free Ca2+ in cultured chick cortical neurons.

Polyamine potentiation and inhibition of N-methyl-D-aspartate (NMDA) receptor-mediated Ca2+ changes was studied in cultured chick cortical neurons. Spermidine and spermine potentiated the effect of saturating concentrations of NMDA and glycine. No effect of spermidine or spermine was observed in the absence of NMDA or in the presence of either kainate or quisqualate. Similarly, antagonism of the NMDA receptor complex with dizocilpine (an open channel blocker), or with competitive antagonists to the NMDA or glycine binding sites greatly attenuated or completely abolished the combined effects of polyamines plus NMDA and glycine. N-Acetylspermine and N-acetylspermidine, in the presence or absence of NMDA and glycine, were without effect. These data strongly suggest that spermidine and spermine are potent and selective agonists at the polyamine binding site. Putrescine and diethylenetriamine were ineffective as antagonists of NMDA-mediated intracellular free Ca2+ increases in the presence or absence of added spermine or spermidine. Arcaine and 1,10-diaminodecane, however, antagonized NMDA-mediated intracellular free Ca2+ increases in the presence and absence of spermine and spermidine, and therefore appear to act either as inverse agonists at the polyamine binding site or as open channel blockers of the NMDA receptor.

Animals↗
PubMed1994

Acute effects of benzodiazepines on operant behavior and in vivo receptor binding in mice.

Lorazepam and alprazolam produced dose-dependent decreases in the rate of fixed-ratio (FR) 20 schedules of food presentation in which either a nose-poke or a lever-press defined the operant and under a fixed-interval (FI) 2-min lever-press schedule of food presentation. In contrast, under FI 2-min and differential reinforcement of low response rate (DRL) 20-s schedules of nose-poke responding for food, intermediate doses of alprazolam produced increases in response rate. Lorazepam, however, only decreased overall response rates under the FI schedule and produced some increases in responding under the DRL schedule. Acute in vivo benzodiazepine receptor binding experiments showed that low to intermediate doses of alprazolam produced significant increases in the binding of [3H]flumazenil in all brain areas tested, while lorazepam produced increases in the brain stem only. The acute effects on binding produced by both drugs were positively and significantly correlated with their acute effects on response rate only under the FR lever-press procedure. These results indicate that the effects of benzodiazepines on in vivo binding may be related to their effects on FR lever-press responding.

Alprazolam↗
PubMed1994

Interaction of central and peripheral benzodiazepine sites in benzodiazepine tolerance and discontinuation.

1. Chronic administration of benzodiazepines is associated with the development of tolerance and discontinuation effects in humans and in a mouse model. 2. Co-administration of compounds active at the "peripheral" benzodiazepine site may alter chronic benzodiazepine effects. 3. During chronic lorazepam administration, addition of the peripheral site antagonist PK11195 attenuates behavioral tolerance and receptor downregulation. 4. In mice treated with both lorazepam and PK11195, discontinuation effects were also attenuated compared to lorazepam alone. 5. Specificity of the action of PK11195 was confirmed by antagonism of its action by the peripheral-site agonist Ro5-4864.

Animals↗
PubMed1994

Prenatal cocaine exposure: increased striatal dopamine transporter binding in offspring at 3 and 6 months of age.

Prior studies indicate that prenatal cocaine exposure can alter dopamine transporter binding in mature mice. To determine the persistence of these effects, pregnant mice were treated with cocaine, 10 mg/kg/d, during days 13 to 20 of gestation and dopamine transporter binding was evaluated in offspring at 3 and 6 months of age. In contrast to prior studies, binding in striatum was significantly increased at both time points in cocaine-exposed mice compared to controls.

Animals↗
PubMed1994

Degradation of methyl bromide by methanotrophic bacteria in cell suspensions and soils.

Cell suspensions of Methylococcus capsulatus mineralized methyl bromide (MeBr), as evidence by its removal from the gas phase, the quantitative recovery of Br- in the spent medium, and the production of 14CO2 from [14C]MeBr. Methyl fluoride fluoride (MeF) inhibited oxidation of methane as well as that of [14C]MeBr. The rate of MeBr consumption by cells varied inversely with the supply of methane, which suggested a competitive relationship between these two substrates. However, MeBr did not support growth of the methanotroph. In soils exposed to high levels (10,000 ppm) of MeBr, methane oxidation was completely inhibited. At this concentration, MeBr removal rates were equivalent in killed and live controls, which indicated a chemical rather than biological removal reaction. At lower concentration (1,000 ppm) of MeBr, methanotrophs were active and MeBr consumption rates were 10-fold higher in live controls than in killed controls. Soils exposed to trace levels (10 ppm) of MeBr demonstrated complete consumption within 5 h of incubation, while controls inhibited with MeF or incubated without O2 had 50% lower removal rates. Aerobic soils oxidized [14C]MeBr to 14CO2, and MeF inhibited oxidation by 72%. Field experiments demonstrated slightly lower MeBr removal rates in chambers containing MeF than in chambers lacking MeF. Collectively, these results show that soil methanotrophic bacteria, as well as other microbes, can degrade MeBr present in the environment.

Biodegradation, Environmental↗
PubMed1994

Isolation, Growth, and Metabolism of an Obligately Anaerobic, Selenate-Respiring Bacterium, Strain SES-3.

A gram-negative, strictly anaerobic, motile vibrio was isolated from a selenate-respiring enrichment culture. The isolate, designated strain SES-3, grew by coupling the oxidation of lactate to acetate plus CO(2) with the concomitant reduction of selenate to selenite or of nitrate to ammonium. No growth was observed on sulfate or selenite, but cell suspensions readily reduced selenite to elemental selenium (Se). Hence, SES-3 can carry out a complete reduction of selenate to Se. Washed cell suspensions of selenate-grown cells did not reduce nitrate, and nitrate-grown cells did not reduce selenate, indicating that these reductions are achieved by separate inducible enzyme systems. However, both nitrate-grown and selenate-grown cells have a constitutive ability to reduce selenite or nitrite. The oxidation of [C]lactate to CO(2) coupled to the reduction of selenate or nitrate by cell suspensions was inhibited by CCCP (carbonyl cyanide m-chlorophenylhydrazone), cyanide, and azide. High concentrations of selenite (5 mM) were readily reduced to Se by selenate-grown cells, but selenite appeared to block the synthesis of pyruvate dehydrogenase. Tracer experiments with [Se]selenite indicated that cell suspensions could achieve a rapid and quantitative reduction of selenite to Se. This reduction was totally inhibited by sulfite, partially inhibited by selenate or nitrite, but unaffected by sulfate or nitrate. Cell suspensions could reduce thiosulfate, but not sulfite, to sulfide. These results suggest that reduction of selenite to Se may proceed, in part, by some of the components of a dissimilatory system for sulfur oxyanions.

Journal Article↗
PubMed1994

Managing provider networks through expert systems: use of patterns of treatment to address overutilization.

Among the most important contributors to rising health care costs is excess utilization of services. Sophisticated clinical criteria, encoded as an expert system in software, allow identification of probable excess utilization in large claims data sets. These systems can be used to adjudicate claims, resulting in direct cost savings, or to profile physicians and other providers, facilitating creation and maintenance of networks. These systems are used by traditional payers to promote quality, control costs, and enhance competitiveness and are beginning to be used by nontraditional payers, such as physician groups and hospital-based networks.

Ambulatory Care↗