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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 235 records · Page 13Linked to original sources
PubMed1999

Effects of the Medicare Alzheimer's disease demonstration on Medicare expenditures.

Applicants were randomized either into a group with a limited Medicare community care service benefit and case management or into a control group receiving their regular medical care. Analyses assess whether or not community care management affected health care use. A tendency toward reduced expenditures was observed for the treatment group, combining all demonstration sites, and when observing each separately. These differences were or approached statistical significance in two sites for Medicare Part A and Parts A and B expenditures averaged over 3 years. Expenditure reductions approached budget neutrality with program costs in two sites.

Adult↗
PubMed1999

Stop the carts.

Nurses and pharmacists at the University of Utah Hospitals & Clinics successfully implement an automated medication distribution system to cut costs, and find they also create measurable process improvements.

Clinical Pharmacy Information Systems↗
PubMed1998

Surface Behavior of Spread Sodium Eicosanyl Sulfate Monolayers.

The surface behavior of spread sodium eicosanyl sulfate monolayers is characterized by determining the dilational moduli from different pi/A isotherms and from surface stress relaxation experiments in the short-time range (<10 min). The elasticities derived from the pi/A isotherms differ depending on the experimental conditions. The quasi-equilibrium isotherm displays a plateau in the range of coexistence of the condensed and the expanded phases and strong increases caused by the formation of a solid-like phase. In contrast, nonequilibrium pi/A isotherms yield effective elasticities showing a maximum within the phase coexistence range. The formation of a solid phase cannot be detected because of the onset of monolayer collapse. Different stress relaxation experiments were carried out for monolayer compression and dilation using transient drop volume jumps. Depending on the experimental run, these experiments lead to consistent and complementary results with those derived from pi/A isotherms under comparable conditions. The stress recoveries yield a relaxation time, a dilation viscosity, and a parameter characterizing the homogeneity of the relaxation process. The stress relaxation is interpreted accounting for both the nonequilibrium between the monolayer and the bulk phase and the nonequilibrium within the monolayer. The influence of alkylsulfate hydrolysis on the presented results was checked. It was found that within the time scale of the experiments no influence of hydrolysis could be detected. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

The 1.1 A resolution crystal structure of [Tyr15]EpI, a novel alpha-conotoxin from Conus episcopatus, solved by direct methods.

Conotoxins are valuable probes of receptors and ion channels because of their small size and highly selective activity. alpha-Conotoxin EpI, a 16-residue peptide from the mollusk-hunting Conus episcopatus, has the amino acid sequence GCCSDPRCNMNNPDY(SO3H)C-NH2 and appears to be an extremely potent and selective inhibitor of the alpha3beta2 and alpha3beta4 neuronal subtypes of the nicotinic acetylcholine receptor (nAChR). The desulfated form of EpI ([Tyr15]EpI) has a potency and selectivity for the nAChR receptor similar to those of EpI. Here we describe the crystal structure of [Tyr15]EpI solved at a resolution of 1.1 A using SnB. The asymmetric unit has a total of 284 non-hydrogen atoms, making this one of the largest structures solved de novo by direct methods. The [Tyr15]EpI structure brings to six the number of alpha-conotoxin structures that have been determined to date. Four of these, [Tyr15]EpI, PnIA, PnIB, and MII, have an alpha4/7 cysteine framework and are selective for the neuronal subtype of the nAChR. The structure of [Tyr15]EpI has the same backbone fold as the other alpha4/7-conotoxin structures, supporting the notion that this conotoxin cysteine framework and spacing give rise to a conserved fold. The surface charge distribution of [Tyr15]EpI is similar to that of PnIA and PnIB but is likely to be different from that of MII, suggesting that [Tyr15]EpI and MII may have different binding modes for the same receptor subtype.

Amino Acid Sequence↗
PubMed1998

The Shake-and-Bake structure determination of triclinic lysozyme.

The crystal structure of triclinic lysozyme, comprised of 1,001 non-H protein atoms and approximately 200 bound water molecules, has been determined ab initio (using native data alone) by the "Shake-and-Bake" method by using the computer program SnB. This is the largest structure determined so far by the SnB program. Initial experiments, using default SnB parameters derived from studies of smaller molecules, were unsuccessful. In fact, such experiments produced electron density maps dominated by a single large peak. This problem was overcome by considering the choice of protocol used during the parameter-shift phase refinement. When each phase was subjected to a single shift of +/-157.5 degrees during each SnB cycle, an unusually high percentage of random trials (approximately 22%) yielded correct solutions within 750 cycles. This success rate is higher than that typically observed, even for much smaller structures.

Crystallography, X-Ray↗
PubMed1998

Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema.

BACKGROUND: Nitrates and furosemide, commonly administered in the treatment of pulmonary oedema, have not been compared in a prospective clinical trial. We compared the efficacy and safety of these drugs in a randomised trial of patients with severe pulmonary oedema and oxygen saturation below 90%. METHODS: Patients presenting to mobile emergency units with signs of congestive heart failure were treated with oxygen 10 L/min, intravenous furosemide 40 mg, and morphine 3 mg bolus. 110 patients were randomly assigned either to group A, who received isosorbide dinitrate (3 mg bolus administered intravenously every 5 min; n=56) or to group B, who received furosemide (80 mg bolus administered intravenously every 15 min, as well as isosorbide dinitrate 1 mg/h, increased every 10 min by 1 mg/h; n=54). Six patients were withdrawn on the basis of chest radiography results. Treatment was continued until oxygen saturation was above 96% or mean arterial blood pressure had decreased by 30% or to below 90 mm Hg. The main endpoints were death, need for mechanical ventilation, and myocardial infarction. The analyses were by intention to treat. FINDINGS: Mechanical ventilation was required in seven (13%) of 52 group-A patients and 21 (40%) of 52 group-B patients (p=0.0041). Myocardial infarction occurred in nine (17%) and 19 (37%) patients, respectively (p=0.047). One patient in group A and three in group B died (p=0.61). One or more of these endpoints occurred in 13 (25%) and 24 (46%) patients, respectively (p=0.041). INTERPRETATION: High-dose isosorbide dinitrate, given as repeated intravenous boluses after low-dose intravenous furosemide, is safe and effective in controlling severe pulmonary oedema. This treatment regimen is more effective than high-dose furosemide with low-dose isosorbide nitrate in terms of need for mechanical ventilation and frequency of myocardial infarction.

Acute Disease↗
PubMed1998

Membrane potassium channels and human bladder tumor cells: II. Growth properties.

These experiments were done to determine the effect of glibenclamide and diazoxide on the growth of human bladder carcinoma (HTB-9) cells in vitro. Cell growth was assayed by cell counts, protein accumulation, and 3H-thymidine uptake. Glibenclamide added at 75 and 150 microM for 48 hr reduced cell proliferation. Dose-inhibition curves showed that glibenclamide added for 48 hr reduced cell growth at concentrations as low as 1 microM (IC50 = 73 microM) when growth was assayed in the absence of added serum. This microM-effect on cell growth was in agreement with the dose range in which glibenclamide decreased open probability of membrane KATP channels. Addition of glibenclamide for 48 hr also altered the distribution of cells within stages of the cell cycle as determined by flow cytometry using 10(-5) M bromodeoxyuridine. Glibenclamide (100 microM) increased the percentage of cells in G0/G1 from 33.6% (vehicle control) to 38.3% (P < 0.05), and it reduced the percentage of cells in S phase from 38.3% to 30.6%. On the other hand, diazoxide, which opens membrane KATP channels in HTB-9 cells, stimulated growth measured by protein accumulation, but it did not increase the cell number. We conclude that the sulfonylurea receptor and the corresponding membrane KATP channel are involved in mechanisms controlling HTB-9 cell growth. However, KATP is not rate-limiting among the signaling mechanisms or molecular switches that regulate the cell cycle.

Cell Division↗
PubMed1998

Lifetime Calculations Relative to Maximum Bubble Pressure Measurements

The theoretical description of maximum bubble pressure experiments needs to consider inertial properties of the gas and liquid. On the basis of an analysis of the time-dependent pressure gradient inside the capillary, bubble lifetime and bubble deadtime are estimated. Numerical calculations of the derived model equations yield different importent dependencies which allow us to better understand bubble pressure experiments at high bubble frequencies: gas flow velocity as function of time, bubble radius as function of time, pressure drop within the capillary as function of time, and bubble lifetime as function of the initial gas velocity. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗
PubMed1998

X-ray crystallographic analysis of the hydration of A- and B-form DNA at atomic resolution.

We have determined single crystal structures of an A-DNA decamer and a B-DNA dodecamer at 0.83 and 0.95 A, respectively. The resolution of the former is the highest reported thus far for any right-handed nucleic acid duplex and the quality of the diffraction data allowed determination of the structure with direct methods. The structures reveal unprecedented details of DNA fine structure and hydration; in particular, we have reexamined the overall hydration of A- and B-form DNA, the distribution of water around phosphate groups, and features of the water structure that may underlie the B to A transition.

Crystallography, X-Ray↗
PubMed1998

Determination of population pharmacokinetic parameters for amikacin in neonates using mixed-effect models.

OBJECTIVE: The population pharmacokinetics of amikacin, in neonates, was investigated using the nonlinear mixed effects model (NONMEM). METHODS: One hundred and six steady-state amikacin serum levels were obtained from 53 black neonates with a mean gestational age of 35.1 weeks and mean age at the start of treatment of 3.1 days. A one-compartment model was used to fit the data. RESULTS: The final models for clearance (CL) and volume of distribution (V) were: CL(l.h(-1)) = 0.031WT(1.45) x P and V(l) = 0.316WT(1.44) where WT = birth weight (kg) and P = 1.28 for girls and 1.0 for boys. Inclusion of other fixed effect parameters in the model did not significantly improve the fit of the data. The inter-individual variability for CL and V were 18% and 13%. respectively. Intra-individual variability was 29%. Mean (95% CI) values of CL, V and half-life were 0.048 (0.045, 0.051) l.h(-1).kg(-1), 0.434 (0.414, 0.453) l.kg(-1) and 6.4 (6.2, 6.6) h respectively. CONCLUSION: Birth weight was an important determinant of both CL and V and, in this data set, gender was also found to influence CL. Mean population pharmacokinetic values were within the range of those previously derived for other neonatal populations using traditional methods.

Amikacin↗
PubMed1998

A model for the determination of carbamazepine clearance in children on mono- and polytherapy.

OBJECTIVE: To derive a model describing carbamazepine (CBZ) clearance in children, in terms of individual patient characteristics. METHODS: One hundred and eighteen steady-state serum carbamazepine concentration measurements were gathered during normal routine care of 72 compliant outpatients (2.3-16.3 years old). Levels were obtained from patients receiving monotherapy (55%), concomitant valproate (26%), or concomitant inducers (phenytoin, phenobarbitone; 19%). A one-compartment model was used to fit the data with the computer programme Nonlinear Mixed Effects Model (NONMEM). RESULTS: Weight, age and concomitant medication were all important determinants of clearance. The final model for clearance (1.h-1) was: CL = [0.7(WT) 0.4] . M, where WT is patient weight (kg) and M is a scaling factor for concomitant medication, with a value of 1 for patients on CBZ monotherapy or concomitant valproate and 1.4 for those receiving concomitant inducers. For the purposes of this analysis, bioavailability (f) was assumed to be complete, i.e., f is thus included in the term CL. CONCLUSIONS: CBZ clearance decreased with increasing age. As age and weight were correlated, either variable was a satisfactory predictor. The influence of both the inducers and valproate on CBZ clearance was as expected. This model, which describes clearance in terms of patient-specific details, can be used when predicting the maintenance dose required to achieve a target mean steady-state CBZ concentration in children.

Adolescent↗
PubMed1998

Cold effect on oxygen uptake, perceived exertion, and spasticity in patients with multiple sclerosis.

OBJECTIVE: To determine the effect of a cold bath (24 degrees C) on oxygen consumption and perceived exertion during ambulation and on spasticity in individuals with mild to moderate multiple sclerosis. DESIGN: A repeated-measures design with random assignment of experimental and control conditions. SETTING: Outpatient physical therapy department associated with an academic institution. PATIENTS: Fourteen individuals with clinically definite multiple sclerosis exhibiting spasticity and capable of ambulating at 0.7 m/sec on a motorized treadmill without handrail support. MEASUREMENT: Assessment of oxygen uptake, heart rate, and perceived exertion occurred during two 10-minute walks interspersed with a 30-minute rest on 2 separate days. Measurement of spasticity occurred three times during each session. RESULTS: Oxygen consumption and perceived exertion were unchanged. Spasticity was higher immediately (p < .05) after the cold bath. CONCLUSIONS: Increase in spasticity was statistically significant, but unlikely to be of any clinical importance. Contrary to our hypothesis, a cold bath (24 degrees C) for 20 minutes did not reduce oxygen consumption or rating of perceived exertion during ambulation.

Adult↗
PubMed1998

Analysis of inter-fragmentary movement as a function of musculoskeletal loading conditions in sheep.

It is well accepted that inter-fragmentary movement influences the fracture healing process. Small axial movement can stimulate callus formation whereas larger shear movement delays the healing process. It is, therefore, essential for optimal fracture healing to minimize shear and to control axial movement. Unfortunately, the complex gap movements are mostly unknown under the large variety of clinical as well as experimental conditions of fracture fixation. To further understand the complex interactions of musculoskeletal loading and inter-fragmentary movements in bones and to reduce the need for animal experiments, a three-dimensional (3D) musculoskeletal model of the left hind limb of a sheep was developed. From 3D ground reaction forces and inverse dynamics, resultant joint loading was determined over a gait cycle. Muscle and joint contact forces were derived from an optimization routine and internal loads in the tibia and metatarsus from beam theory. Finally, inter-fragmentary movements were calculated from the bony loading condition and experimentally determined stiffness matrices of monolateral AISF external fixator constructs. Both the joint contact forces at the hip and gap movement of a mid-shaft tibial fracture agree with in vivo data reported in the literature. The bones proved to be mainly axially loaded with slightly increasing shear forces toward their ends. The results suggest that inter-fragmentary movement of metatarsal fractures is fairly independent of the fracture location whereas the movement increases in proximal tibial fractures compared to those in the distal and diaphyseal tibia. Considerable shear movement was found for all locations and external fixator mountings. However, shear movement could be minimized with a cranio-lateral rather than a cranio-medial shift from the cranial fixator plane.

Animals↗
PubMed1998

Dopamine D1-like receptors and reward-related incentive learning.

There now is general agreement that dopaminergic neurons projecting from ventral mesencephalic nuclei to forebrain targets play a critical role in reward-related incentive learning. Many recent experiments evaluate the role of dopamine (DA) receptor subtypes in various paradigms involving this type of learning. The first part of this paper reviews evidence from these studies that use antagonists or agonists relatively specific for D1- or D2-like receptors in operant paradigms with food, brain stimulation, self-administered stimulant or conditioned rewards or place conditioning. The focus is on studies that directly compare agents acting at the two DA receptor families, especially those studies where the agents produce differential actions. Results support the conclusion that D1-like receptors play a more critical role in reward-related learning than D2-like receptors. D1-like receptors initiate a cascade of intracellular events including cyclic adenosine monophosphate (cAMP) formation and activation of cAMP-dependent protein kinase (PKA). The final section of this paper reviews evidence from a wide range of neuroscience experiments that implicates the cAMP/PKA pathway in learning in general and in reward-related incentive learning in particular. We conclude that the molecular mechanism underlying DA-mediated incentive learning may involve DA release in association with reward, stimulation of D1-like receptors, activation of the cAMP/PKA cascade and additional intracellular events leading to modification of cortico-striatal glutamatergic synapses activated by stimuli encountered in close temporal contiguity with reward. Thus, when reward-related incentive learning takes place, it may be the action of DA acting at D1-like receptors that leads to plastic changes in the striatum that form the substrate of that learning.

Animals↗