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J A Lewis

Publications and source records attributed to J A Lewis.

At least 19 recordsLinked to original sources
PubMed1992

Computer simulation for the prediction of separation as a function of pH for reversed-phase high-performance liquid chromatography. I. Accuracy of a theory-based model.

Computer simulation software (DryLab I/mp) is described for predicting high-performance liquid chromatographic separation as a function of changes in mobile phase pH. Three experimental runs with pH (only) varied are used to derive values of pKa plus capacity factors (k') for the ionized and non-ionized form of each ionizable solute. Various tests of the experimental data then allow classification of each solute as acidic, basic, neutral (including strong or weak acids or bases) and amphoteric. Experimental data are reported for the separation of several substituted anilines as a function of pH and solvent composition (%B). Experimental requirements for the accurate prediction of separation (ca. +/- 2-4% in alpha) as a function of pH are discussed. The reliability of the software is demonstrated for three different samples: mixtures of (a) substituted benzoic acids, (b) substituted anilines and (c) catecholamine-related compounds.

Aniline Compounds↗
PubMed1992

Computer simulation for the prediction of separation as a function of pH for reversed-phase high-performance liquid chromatography. II. Resolution as a function of simultaneous change in pH and solvent strength.

The optimization of reversed-phase high-performance liquid chromatographic separation by the simultaneous variation of pH and solvent strength (%B) was studied for acidic (substituted benzoic acids) and basic samples (substituted anilines). The combination of these two variables was expected to be more useful than either variable alone. This proved to be the case for the benzoic acid sample, but not for the aniline sample. Column plate numbers were also studied for each sample and as a function of pH. With the exception of one compound (3,5-dimethylaniline) in one particular pH range (3.0-4.5), plate numbers of 12,000-20,000 were observed for each sample.

Aniline Compounds↗
PubMed1992

Epanolol as a model for assessing patient preference in anti-anginal drug therapy.

Since drug therapy of angina is likely to produce a similar degree of efficacy for most drugs in common use, treatment choice should additionally focus on other factors, notably adverse events, quality of life, and convenience. Improvements in these factors can also lead to better compliance and can aid the doctor by cutting down the number of patient visits required to optimize therapy. The authors have evaluated the patient's overall assessment of symptomatic relief and adverse experiences in a comparative manner by means of the two-period crossover design using the patient's declared treatment preference as the primary measurement. This encapsulates several factors in a single assessment that can be understood by both physician and patient. The authors carried out two such studies of epanolol (Visacor), a novel anti-anginal agent with both beta-1 selective antagonist activity and also beta-1 selective partial agonist activity. In one study (n = 608) the comparator was metoprolol, and in the other (n = 571) it was nifedipine. This article describes and evaluates the methodology of these studies. To assess preference optimally, each patient had to receive both treatments in short but clinically relevant treatment periods, with no washout. Re-entry into the second period, after withdrawal from the first, was permitted. Both studies showed advantages for epanolol, more marked in the case of nifedipine, arising from equivalent efficacy but fewer adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1992

Safety profile and immunogenicity of an inactivated vaccine derived from an attenuated strain of hepatitis A.

To determine the safety and immunogenicity of an inactivated hepatitis A vaccine, 56 healthy adult volunteers were randomly assigned to receive an intramuscular injection of 6.3, 12.5 or 25 ng of inactivated hepatitis A vaccine or placebo at 0, 2 or 4, and 24 weeks. Adverse reactions occurred with similar frequency in vaccine and placebo recipients and consisted primarily of pain or tenderness at the injection site. By 4 weeks after a single 6.3, 12.5 or 25 ng injection, seven, nine and ten out of ten vaccinees, respectively, had antibody detectable by a HAV AB assay modified to increase its sensitivity tenfold. All vaccinees had antibodies detectable by this assay within 2 weeks of their second inoculation. Geometric mean antibody levels increased with higher doses of vaccine (p = 0.05). Neutralizing antibody was detected within 4 weeks of a single inoculation in all vaccinees. Neutralizing antibody was detected after the third inoculation at dilutions of greater than or equal to 1:2048 in all 12.5 and 25 ng vaccinees. All 19 vaccinees tested at 24 months still had HAV antibodies detectable by a modified HAV AB assay. This inactivated hepatitis A vaccine appears to be well tolerated and immunogenic at doses of 6.3-25 ng. The choice of dose and vaccination schedule may depend on the rapidity with which seroconversion is desired.

Adolescent↗
PubMed1992

A detergent-solubilized nicotinic acetylcholine receptor of Caenorhabditis elegans.

We have used a spin column assay to study the detergent-solubilized levamisole receptor, a nicotinic acetylcholine receptor of the nematode Caenorhabditis elegans. The receptor can be successfully solubilized in detergent solutions of Triton X-100, Lubrol PX, or sodium cholate. Centrifugal gel filtration assay using the tritiated ligand [3H]meta-aminolevamisole ([3H]MAL) provides a greater signal and a better signal-to-noise ratio for soluble levamisole receptor binding than either polyethylene glycol precipitation or DEAE filter assay with the same ligand. As for membrane-bound receptor, the detergent-solubilized levamisole receptor consists of more than one affinity state. Detergent solubilization appears to increase the affinity of all states for [3H]MAL (Kd for the highest affinity solubilized [3H]MAL binding state, 41 +/- 5 pM). Data is presented on the equilibrium binding and the association and dissociation reaction rates of the receptor. The similar relative efficacy with which various compounds inhibit specific [3H]MAL binding and deficiencies in solubilizable high affinity specific [3H]MAL binding in two receptor mutants show that the solubilized receptor is the same nicotinic acetylcholine receptor that is detected by assaying membrane-bound specific [3H]MAL binding. The detergent-solubilized levamisole receptor is stable at 0 degree to 4 degrees C, making receptor purification feasible.

Animals↗
PubMed1992

Protein starvation impairs the ability of activated lymphocytes to produce interferon-gamma.

The impairment of lymphocyte function in nutritionally deprived rats was studied. Lymphocytes from rats fed a diet lacking protein showed a severe decrease in their ability to proliferate when stimulated with mitogens. This was accompanied by a dramatic inhibition of interferon-gamma (IFN-gamma) production and a lesser decrease in the release of interleukin-2 (IL-2). Analysis of RNA levels by Northern blot hybridization confirmed that lymphocytes from protein-starved rats had lower levels of mRNAs for IFN-gamma, IL-2, and IL-2 receptor than those from control animals. Protein deprivation therefore leads to a modification of lymphocyte function such that IFN-gamma production in particular is severely impaired.

Animals↗
PubMed1992

A review of chest physiotherapy in neonatal intensive care units in Australia.

Clinical techniques and protocols for chest physiotherapy vary greatly from one Neonatal Intensive Care Unit to another. In 1988 a questionnaire designed to investigate differing techniques used was distributed to Neonatal Intensive Care Units (NICU) around Australia. Fourteen of the 15 questionnaires were completed and returned. The results revealed that the methods of chest treatment and the indicators for commencing chest treatment were similar throughout NICU. Both physiotherapists and nursing staff played a role in the performance of chest treatment in all but one unit where it was the responsibility of nursing staff. However, the area in which there was most variability between NICU was the individual treatment protocols employed pre- and postextubation of the neonate. A review of literature over the past 10 years also demonstrates variability in chest physiotherapy. It was concluded that further well-controlled studies with larger sample sizes are needed to validate the use of chest physiotherapy for the neonate, especially in relation to the techniques and specific protocols employed.

Australia↗
PubMed1991

The analysis of failure time data in crossover studies.

Clinical trials of new drugs in the treatment of angina pectoris frequently make use of exercise tests to evaluate efficacy. The crossover design is often employed. The methods commonly used to analyse the various exercise times, for example, 'time to pain', are insensitive and potentially biased by the manner in which they deal with the censored nature of the data. Survival analysis can be adapted for use in crossover trials, both in a relatively simple way, and also through the full power of the Cox model. This is considerably more sensitive and not subject to the same bias. This methodology leads to the use of median survival times to illustrate treatment effects and this provides a practical interpretation of clinical relevance. The estimation of median survival times in crossover trials poses some special problems. The methodology is illustrated throughout by means of a specific two-period example in which atenolol was compared with the combination of atenolol and nifedipine. The three-period design is also briefly discussed.

Analysis of Variance↗
PubMed1991

Three-point versus two-point method for early individualization of aminoglycoside doses.

An approach using two serum concentrations following the initial dose of an aminoglycoside was retrospectively evaluated using the first and third samples from all three-point studies conducted by the pharmacokinetic consult service in 1988. The same Sawchuk and Zaske method was used for the three-point and two-point studies. Although the predicted peaks and troughs from the two-point study were statistically different from those of the three-point study, it is the authors' opinion that the root mean squared error of 0.38 mg/L (95% confidence interval [CI] 0.31-0.45) for the peaks and 0.09 mg/L (95% CI 0.06-0.11) for troughs is well within the limits of acceptable clinical error for gentamicin and tobramycin. Eliminating one-third of initial aminoglycoside concentrations could result in significant time and cost savings.

Aminoglycosides↗
PubMed1990

Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant.

The principal neutralizing determinant (PND) of human immunodeficiency virus HIV-1 is part of a disulfide bridged loop in the third variable region of the external envelope protein, gp120. Analysis of the amino acid sequences of this domain from 245 different HIV-1 isolates revealed that the PND is less variable than thought originally. Conservation to better than 80 percent of the amino acids in 9 out of 14 positions in the central portion of the PND and the occurrence of particular oligopeptide sequences in a majority of the isolates suggest that there are constraints on PND variability. One constraining influence may be the structural motif (beta strand--type II beta turn--beta strand--alpha helix) predicted for the consensus PND sequence by a neural network approach. Isolates with a PND similar to the commonly investigated human T cell lymphoma virus IIIB (HTLV-IIIB) and LAV-1 (BRU) strains were rare, and only 14 percent of sera from 86 randomly selected HIV-1 seropositive donors contained antibodies that recognized the PND of these virus isolates. In contrast, over 65 percent of these sera reacted with peptides containing more common PND sequences. These results suggest that HIV vaccine immunogens chosen because of their similarity to the consensus PND sequence and structure are likely to induce antibodies that neutralize a majority of HIV-1 isolates.

Amino Acid Sequence↗
PubMed1990

Meta-analysis of value of propranolol in prevention of variceal haemorrhage.

A meta-analysis of all controlled clinical trials of beta-adrenoceptor blocking drugs, principally propranolol, in the prevention of primary or secondary variceal bleeding has shown that beta-blockade significantly reduced the occurrence of variceal bleeding, deaths from variceal bleeding, and overall mortality. There was some heterogeneity between trials in the effect of beta blockade on secondary prevention. When only fully reported, randomised, placebo-controlled studies were included the heterogeneity disappeared, and the reductions in bleeding episodes and mortality became more striking. Separate analyses of primary and secondary prevention studies also showed clear reductions in occurrence of variceal bleeding and deaths. These results seem to indicate the value of beta-adrenoreceptor blocking drugs for the primary prevention of haemorrhage from large oesophageal varices. However, there is still a need for large multicentre trials of beta-blockade for primary prevention of variceal bleeding in patients without large varices and of comparisons between beta-blocker therapy with other treatments in secondary prevention.

Adrenergic beta-Antagonists↗
PubMed1990

Interferon selectively inhibits the expression of mitochondrial genes: a novel pathway for interferon-mediated responses.

As an approach to identifying genes involved in physiological actions of interferons we used differential probes to screen a cDNA library from mouse L-929 cells treated with interferon alpha/beta. We identified two negatively regulated mRNA species which have been examined by analysis of the corresponding mRNAs and by DNA sequencing. Comparison with the GenBank database showed that these cDNA clones corresponded to mitochondrially encoded genes for cytochrome b and subunit I of cytochrome c oxidase. A further cDNA encompassing three mitochondrial genes was used as a probe to show that a third mRNA, NADH dehydrogenase subunit 5, was also down-regulated by interferon while a fourth, NADH dehydrogenase subunit 6, was unaffected. Expression of cytochrome b was also inhibited in mouse NIH 3T3 cells treated with interferon alpha/beta and in human Daudi lymphoblastoid cells treated with interferon alpha. The ability of interferon to reduce mitochondrial mRNA levels could be blocked by cycloheximide suggesting that these effects are mediated by an interferon-responsive nuclear gene which encodes a product capable of regulating mitochondrial gene expression. Analysis of proteins synthesized in the presence of emetine, a specific inhibitor of cytoplasmic translation, showed that the synthesis of several mitochondrial translation products, including cytochrome b, was reduced after treatment with interferon. Our results reveal a novel effect of interferon on cellular physiology which could have important consequences for understanding the effects of interferons as well as suggesting new mechanisms for the regulation of mitochondrial biogenesis and function.

Animals↗