PubMed Health⌕ Search

Biomedical subjects

D A Stephens

Publications and source records attributed to D A Stephens.

At least 19 recordsLinked to original sources
PubMed2000

Identification of a yellow impurity in aged samples of aqueous butamben suspension: evidence for the oxidative degradation of poly(ethylene glycol).

Butamben (butyl p-aminobenzoate) has been formulated to provide long-acting treatment for chronic pain. The suspension, which contains poly(ethylene glycol) and polysorbate 80, was found to yellow under ambient conditions if not adequately protected from oxygen. The impurity responsible for the color was isolated and identified on the basis of nuclear magnetic resonance spectroscopy and mass spectrometry. The compound is an oxalamidine, which is formally the condensation product of oxalic acid with four equivalents of butamben, and may be formed by the reaction of butamben with an oxidation product of poly(ethylene glycol).

Benzocaine↗
PubMed1999

The Bayesian analysis of a pivotal pharmacokinetic study.

The aim of this paper is to carry out a detailed Bayesian population pharmacokinetic analysis of a three-period cross-over study of the drug fluticasone propionate carried out in 12 healthy male volunteers. The study was carried out to characterize the pharmacokinetics of the drug, in particular to investigate dose proportionality. We examine the appropriateness of modelling assumptions via a variety of diagnostic techniques. We also examine the effect of deleting time points at which the concentration was recorded as below the limit of quantification, as opposed to including these points as censored observations. We assess dose proportionality before carrying out a final combined analysis of data from all three doses.

Adult↗
PubMed1996

Estimating linkage heterogeneity.

The admixture model for linkage heterogeneity is modified to take account of the difference in recombination fractions in the two sexes. The data used may concern a single (marker) locus on one chromosome, which is suspected of being sometimes near a (disease) locus for a particular condition of interest, or there may be data on more than one locus on this chromosome. There may be data on a locus or loci on a second chromosome, which is also suspected of sometimes carrying an allele for the condition in question. The general principle for the analysis is the same in all such cases, though details may differ. The object is to estimate the relevant recombination fractions, and the proportions of cases in which the allele for the condition falls on each chromosome.

Chromosomes, Human, Pair 16↗
PubMed1995

Estimating multipoint recombination fractions.

The likelihood in linkage investigations can be expressed as a polynomial in the relevant recombination fractions. With polymorphic characters, this can be reduced to a product of separate factors for female and male recombinations, with only mild loss of information. With three generation data the polynomials take a specially simple form. Algorithms are given for finding maximum likelihood estimates and their standard errors.

Female↗
PubMed1993

Bayesian inference in multipoint gene mapping.

The problem of ordering and mapping genes on the basis of recombinant data and radiation hybrid data is formulated as a problem of Bayesian inference for an unknown permutation. The challenging computational problems posed by this approach are shown to be resolvable using Markov chain Monte Carlo methods.

Algorithms↗
PubMed1990

Ribozymes as potential anti-HIV-1 therapeutic agents.

Certain RNA molecules, called ribozymes, possess enzymatic, self-cleaving activity. The cleavage reaction is catalytic and no energy source is required. Ribozymes of the "hammerhead" motif were identified in plant RNA pathogens. These ribozymes possess unique secondary (and possibly tertiary) structures critical for their cleavage ability. The present study shows precise cleavage of human immunodeficiency virus type 1 (HIV-1) sequences in a cell-free system by hammerhead ribozymes. In addition to the cell-free studies, human cells stably expressing a hammerhead ribozyme targeted to HIV-1 gag transcripts have been constructed. When these cells were challenged with HIV-1, a substantial reduction in the level of HIV-1 gag RNA relative to that in nonribozyme-expressing cells, was observed. The reduction in gag RNA was reflected in a reduction in antigen p24 levels. These results suggest the feasibility of developing ribozymes as therapeutic agents against human pathogens such as HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Direct detection of HIV-1 RNA from AIDS and ARC patient samples.

Human immunodeficiency virus (HIV), formerly termed human T-lymphotropic virus (HTLVIII/LAV), is the etiological agent of acquired immune deficiency syndrome (AIDS). Direct detection of HIV-1 nucleic acid sequences in patient tissue or blood samples is possible in only a minor fraction of cases due to the low percentage of infected cells (Shaw et al., 1984). We report a modification of the polymerase chain reaction method (PCR) (Saiki et al., 1985), in which we amplify sequences from HIV-1 RNA templates, for the identification of HIV-1 in peripheral blood and tissue samples obtained from AIDS and AIDS-related complex (ARC) patients. This method of HIV-1 detection is at least six orders of magnitude more sensitive than standard nucleic acid detection methods and has direct clinical applications. In vitro tissue culturing of the virus is not required for HIV-1 detection. Using this technique, the sequence in the orfB region of HIV-1 has been amplified and detected from less than 1 microgram of total RNA prepared from a few milliliters of peripheral blood samples. This technique enables the rapid and unambiguous clinical detection of potential HIV-infected individuals and can be used to assay the efficacy of anti-HIV-1 drugs. To enhance the efficiency of this technique, we have appended the prokaryotic T7 RNA polymerase promoter sequence to one of the priming oligonucleotides. After several cycles of PCR with the promoter-containing oligo, a small aliquot of the reaction can be utilized to direct specific and efficient T7 RNA polymerase-mediated transcription of the amplified sequences, thus enhancing the sensitivity and simplifying the labor of the experiment.

AIDS-Related Complex↗
PubMed1988

Inhibition of human immunodeficiency virus by using an oligonucleoside methylphosphonate targeted to the tat-3 gene.

Antiviral effects were characterized for two oligodeoxyribonucleoside methylphosphonates synthesized in an antisense (3'-TCTTAACC-5') or a sense (5'-AGAATTGG-3') orientation, based on the RNA sequence of the first splice acceptor site of the tat-3 gene of human immunodeficiency virus (HIV) (5'...AGAAUUGG...3'). The development of syncytial cells and supernatant reverse transcriptase was inhibited by a single exposure to the antisense HIV, and HIV RNA synthesis was inhibited by both antisense and sense methylphosphonates but not by a control herpes simplex virus antisense sequence.

Antiviral Agents↗
PubMed1988

Pericardial fat necrosis.

Pericardial fat necrosis has a highly characteristic clinical picture that enables a preoperative diagnosis to be made on clinical grounds. Surgical therapy, which remains the treatment of choice for this curable entity, confirms the diagnosis. This report reviews the literature and adds a thirteenth documented case to the previously reported 12 cases.

Adult↗
PubMed1987

Evidence that cyclosporine does not inhibit allograft rejection by IL-2-treated sensitized splenocytes.

Splenocytes sensitized in vitro to the H-2 allotype of a skin allograft have been shown to cause accelerated rejection of the skin allograft after adoptive transfer of the splenocytes. Treatment of the host with splenectomy or sublethal radiation did not alter the accelerated rejection. In the present study, cyclosporine (CsA) given subcutaneously to mice bearing 1 day old skin grafts prevented the rejection of the graft despite the adoptive transfer of sensitized cells. If the CsA was given for 14 days at 50 mg/kg every other day, the grafts were rejected an average of 6 days after the cessation of CsA. If the CsA was given for 20 days 50 mg/kg every other day, the grafts were not rejected even after cessation of CsA. When no sensitized cells were given, the same pattern resulted; that is, when a 14 day course of CsA was given the grafts were rejected after cessation of the CsA but when a 20-d course was given, the grafts were not rejected even after the CsA was stopped. If splenocytes were sensitized in the presence of interleukin-2 (IL-2), they caused rejection of the skin allografts in animals even on treatment with CsA. We concluded that CsA can prevent skin allograft rejections in the murine system. Moreover, the dose of CsA was critical, in that a longer course of CsA was necessary for tolerance. CsA further prevented the accelerated rejection of skin allografts by adoptive transfer of specifically sensitized splenocytes. Donor irradiation did not alter the effect of the CsA or of the adoptively transferred cells. CsA could not prevent the rejection of skin allografts when the adoptively transferred cells were sensitized to antigen in the presence of IL-2.

Animals↗
PubMed1984

Factors associated with a good response to lithium in aggressive mentally handicapped subjects.

Twenty-five (25) mentally handicapped in-patient adults with persistent aggressive behaviour took part in a double-blind crossover trial lasting 5 months comparing the effects of lithium with placebo on aspects of aggressive behaviour. All patients were receiving neuroleptic and/or anticonvulsant drugs which were continued during the trial. Seventeen (17) of the patients showed greater improvement during the lithium phase compared to placebo. Multiple regression analysis was carried out to determine which of 17 background variables were related to outcome. The following factors were associated with a good response to lithium: less than one aggressive episode per week before starting treatment, overactivity, stereotypic behaviour, female sex and epilepsy. No patient became toxic during the investigation although lithium levels were maintained within the therapeutic range (0.5-0.8 mmol/l).

Adolescent↗
PubMed1984

Trazodone. A comparative clinical and predictive study.

The clinical efficacy and tolerability of trazodone and amitriptyline were compared in 74 hospital patients suffering from depressive illness. The daily doses of trazodone and amitriptyline were 150-300 mg and 75-225 mg, respectively, with half-strength capsules for patients over the age of 65 years. Twenty-five and 29 patients receiving trazodone and amitriptyline, respectively, completed the 6 week treatment period. Antidepressant activity was measured using the Hamilton Depression Rating Scale (HDRS), the Zung Scale of Depression, visual analogue scales and a Global Assessment Scale. Trazodone and amitriptyline were both effective but not statistically different from each other in terms of antidepressant action. Moreover, patients with neurotic or endogenous depression responded equally well on either treatment. Trazodone was less troublesome in respect of the persistent dry mouth and severe adverse psychiatric reactions which occurred with amitriptyline. Patients should be advised to take trazodone after meals.

Adult↗