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Biomedical subjects

M E Lacy

Publications and source records attributed to M E Lacy.

9 recordsLinked to original sources
PubMed1994

Antiresorptive drugs and trabecular bone turnover: validation and testing of a computer model.

A computer model of trabecular bone turnover has been developed, based on concepts of Jonathan Reeve [1]. This model predicts changes in bone volume by summing bone resorption and formation over a large number of remodeling sites. Clinical data [histomorphometry and bone mineral content (BMC)] from two clinical studies using an antiresorptive drug (etidronate disodium, EHDP) in postmenopausal osteoporosis were used to test the model. The results for BMC obtained from the EHDP and placebo groups in each study at 60 and 120 weeks were correctly predicted by the model from the histomorphometric data obtained from baseline and week 60 biopsies. The parameter in this model having the greatest influence on predicted changes in bone volume was found by sensitivity analysis to be activation frequency. These results suggest that the contribution of bone turnover to BMC can be predicted solely by considering the cell kinetics of the basic multicellular unit (BMU), and that, in the case of antiresorptive drugs, maximal effects on bone volume may be achieved by pharmacological reduction of activation frequency. The results also suggest that the present model may be useful in predicting in clinical studies the effects of EHDP and similar drugs on bone turnover.

Absorptiometry, Photon↗
PubMed1990

Method validation revisited: a chemometric approach.

A validation procedure is presented that satisfies the FDA requirements of accuracy (including precision repeatability), sensitivity, linearity, dynamic range, and homoscedasticity, all with a single set of data. The procedure utilizes the corrigible error correction (CEC) technique comprised of three response curves--standard, Youden one-sample, and method of standard additions (MOSA) plots, from a total of 15 to 18 X,Y data pairs. For the bias component of accuracy, the systematic bias error of the method is quantitatively separated into its constant and proportional error components. The overall constant systematic error is further separated into the system (blank) and analyte-matrix (sample) components. The CEC data also provide an internal, i.e., in situ corrected assay for the sample for comparison with alternative method data. Statistical diagnostic tests are used for the final evaluation of the method acceptability, specifically in deciding whether or not the systematic error indicated requires a root source search for its removal or is simply a calibration constant of the method.

Administration, Topical↗
PubMed1986

Efficacy of dantrolene sodium in management of tetanus in children.

The effectiveness of dantrolene sodium in controlling tetanic spasms was evaluated in 21 children (aged 4 days-13 years) with tetanus. These dantrolene-treated patients were compared with an historical control group of 26 children previously treated for tetanus by traditional means at the same institution. The groups were comparable in terms of age, other treatments, and severity of disease. All patients received standard treatments for tetanus, including sedatives, antibiotics, and tetanus-immune globulin. Patients in the dantrolene-treated group also received dantrolene, either intravenously (Dantrium Intravenous) or orally, in divided doses totalling 4-6 mg/kg/day. Mortality was 73% (neonates 83%, non-neonates 50%) in the control group, compared with 33% (neonates 50%, non-neonates 0%) in the dantrolene-treated group. Dantrolene did not cause additional respiratory depression when administered alone or in combination with other drugs routinely used to treat tetanus. In this study, the use of dantrolene with traditional conservative therapy significantly reduced mortality from tetanus.

Adolescent↗
PubMed1984

Computer modeling of the recombination reaction of rhodopsin.

Various mechanistic schemes for the recombination reaction of rhodopsin were designed and tested using computer modeling and simulation with data from kinetics experiments. The reaction schemes were mathematically modeled by systems of nonlinear first-order ordinary differential equations (ODEs) with unknown rate constants. Each model was fitted to the experimental data by using a modified simplex algorithm for parameter (rate constant) estimation and Gear's method for solving stiff systems of ODEs. The recombination reaction of rhodopsin was best modeled by branched, multistep reaction schemes which included formation of noncovalent complexes, acid-base equilibria, and acid and base-catalyzed dehydration of a Schiff base intermediate. The biochemical bases for these models are discussed.

Animals↗
PubMed1984

Regeneration of rhodopsin and isorhodopsin in rod outer segment preparations: absence of effect of solvent parameters.

Regeneration of rhodopsin and isorhodopsin from bleached bovine rod outer segment suspensions and 11- or 9-cis retinal occurs at similar rates (second-order rate constants of 1000 M-1s-1 and 900 M-1s-1, respectively) and to a similar extent (maximal regeneration at pH 5.5-7.0). Formation of both pigments follows pseudo-first order kinetics in an excess of retinal at pH 7.0. These results suggest that the mechanisms of regeneration are similar for the 11-cis and 9-cis retinal isomers. Solvent ionic strength, buffer concentration, viscosity, and polarity have no significant effect on the rate of pigment formation, providing further evidence that the retinal binding site in bleached bovine rod outer segments is well protected from the hydrophilic environment.

Animals↗
PubMed1982

Inhibition of rhodopsin regeneration by cyclohexyl derivatives.

Twenty two compounds, bearing some structural similarity either to the ring-end or aldehyde-end of 11-cis-retinal, have been screened for their effectiveness in decreasing the rate of regeneration of rhodopsin in vitro from 11-cis retinal and bovine opsin. The results of these experiments indicate that only those compounds containing a ring and having at least two methyl groups at the 1,5-ring positions are capable of decreasing the rate of regeneration of rhodopsin. Short-chain aldehydes resembling the aldehyde-end of retinal did not affect the rate of pigment formation. There was no additive effect of combining a dimethylcyclohexyl inhibitor and a short chain aldehyde. The methyl groups at the 1,5-positions may play a special role in anchoring the retinal into the protein binding site. This hypothesis is supported by the failure of the ring demethylated analogue, 11-cis, 1,1,5-desmethyl-5,6-dihydroretinal, to form pigment under the same conditions with which good pigment yields are obtained with 11-cis 5,6-dihydroretinal.

Binding Sites↗
PubMed1981

Neuromelanin: a hypothetical component of bioelectronic mechanisms in brain function.

Several lines of evidence suggest the involvement of bioelectronic mechanisms in brain function. Although no components of such mechanisms have been identified, neuromelanin is a likely candidate. The functional significance of neuromelanin is supported by considerable published work, herein reviewed. Certain electronic properties of melanin, notably in stable free radical characteristics and its semiconduction, may be influenced by alpha-MSH, ACTH 4-10, and melatonin. Neuron function may be influenced in turn by the effect of semiconduction on synaptic transmission. Thus neuromelanin may be an important part of a complex neural modulation system.

Animals↗