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Biomedical subjects

D Clark

Publications and source records attributed to D Clark.

At least 127 records · Page 7Linked to original sources
PubMed1995

Effects of the dopamine autoreceptor antagonist (-)-DS121 on the discriminative stimulus properties of d-amphetamine and cocaine.

(-)-DS121 [S-(-)-3-(3-cyanophenyl)-N-n-propyl piperidine) is a recently synthesised phenylpiperidine derivative suggested to be a dopamine receptor antagonist acting preferentially at dopamine autoreceptors. The drug exerts 'agonist-like' behavioural effects by enhancing dopamine release, but also shares properties in common with neuroleptics. The ability of (-)-DS121 to both generalise to and antagonise the stimulus effects of psychostimulants was determined in rats trained to discriminate d-amphetamine (0.5 mg/kg) or cocaine (5.0 mg/kg) from saline in a two-lever, food-reinforced, drug discrimination task. (-)-DS121 (3.5-14.0 mg/kg) produced small, but significant, increases in drug lever-appropriate responding in both d-amphetamine and cocaine-trained rats. However, there was no indication of a dose-dependent effect in either case. On the other hand, (-)-DS121 dose-dependently reduced response rate. Caffeine produced a higher level of drug lever-appropriate responding than (-)-DS121 in d-amphetamine-trained rats. (-)-DS121 (7.0-14.0 mg/kg) also weakly antagonised the cueing properties of both d-amphetamine and cocaine. A marked response disruption with the drug combination precluded testing of higher doses of (-)-DS121. A combination of subthreshold doses of (-)-DS121 (3.5 mg/kg) and d-amphetamine (0.0625 mg/kg) produced a significant degree of drug lever-appropriate responding, suggesting a synergistic interaction between these drugs. However, such an interaction was not noted with a higher dose of (-)-DS121, or when this drug was administered with a low dose of cocaine (0.25 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1995

Priority setting in health care: an axiomatic bargaining approach.

This paper examines how axiomatic bargaining theory can be used to analyze different rules for dividing the health care budget between two patients. This approach allows an explicit statement of the assumptions underlying the division rules and also provides a general characterization of the consequences of using these rules when the opportunity set (or number of patients) changes.

Budgets↗
PubMed1995

Contracting for palliative care.

In this paper the role of purchasing authorities, as set out in the current U.K. policy literature, is reviewed in the context of recent developments in palliative care. The notion of the purchasing cycle, from need assessment and strategic planning through to contracting and monitoring is outlined, along with core features of recent health and social care legislation in Britain: quality assurance, consumer choice and value for money. The role of providers and service users in the purchasing process is examined and the relationship between purchasers across the health/social care divide is explored. The implications of contracting for the voluntary sector provision of palliative care are also assessed. The review highlights the difficulties under the new legislation in reconciling the aim of efficiency with that of quality assurance, and of separating out the roles of purchasers and providers in a context where palliative care service developments have been provider-led. These factors reinforce the requirement to turn the purchaser-provider split into an effective partnership. Finally, the review highlights the need to address the current imbalances in the purchasing cycle by giving adequate attention to aggregate need assessment and strategic planning.

Contract Services↗
PubMed1995

IASP task force on euthanasia and assisted suicide.

The first meeting of the IASP Task Force on Euthanasia and Assisted Suicide took place in Venice on June 7, 1995. Several interested observers were present. It was decided that at the public IASP meeting the following day each speaker should address, briefly, the current legal situation and the pressure for change, as well as give a personal statement. David Clark spoke for North America, Bob Goldney for Australia, Michael Kelleher for Britain and Ireland, Jerzy Wasserman for Scandinavia, and Hans Wedler for the German-speaking world. Their views are published in this article. Ad Kerkhof requested that the Dutch television film "Death on Request" be discussed. The committee was of the opinion that clear definitions were essential. In their view, these should take into account the differences between active and passive euthanasia, as well as between professionally assisted and lay-assisted suicide.

Australia↗
PubMed1995

An audit of methotrexate and folic acid for rheumatoid arthritis. Experience from a teaching centre.

We describe an audit of 158 patients with RA treated with weekly methotrexate and 5 mg of folic acid 24 h later. Our aim was to assess the safety and efficacy of this regime in our hands compared with published clinical trials of methotrexate in RA, and to examine patient outcomes. Treatment improved ESR, but only 69% of patients continuing therapy for prolonged periods believed their arthritis to be better on treatment. Health Assessment Questionnaire and Hospital Anxiety and Depression questionnaire scores in prospectively studied patients were not significantly altered by treatment. Toxicity occurred frequently (59% in those continuing and 89% in those ceasing therapy) and cessation of therapy solely due to lack of efficacy was rare. The probability of patients continuing with methotrexate and folic acid after 1, 2, 3 and 4 yr was 87, 76, 74 and 74%, respectively, figures that are at the upper end of the reported range for methotrexate alone.

Adult↗
PubMed1995

Construction of intertypic chimeric dengue viruses exhibiting type 3 antigenicity and neurovirulence for mice.

There are four dengue virus serotypes (DEN1 to -4), each of which causes major epidemics in tropical or subtropical areas. The current strategy for dengue virus immunization favors the use of a tetravalent vaccine preparation. We have previously employed full-length DEN4 cDNA to construct a viable intertypic dengue virus type 1 or type 2 chimera that contained the C-PreM-E or only the PreM-E genes of DEN1 or DEN2 substituting for the corresponding genes of DEN4. This success implied that it might be possible to create mutants of all four dengue virus serotypes for evaluation as candidate vaccines. In this study, we constructed DEN3-DEN4 chimeras that contained DEN3 C-PreM-E genes and expressed DEN3 antigenic specificity. Unlike our previous successes in cloning DEN1 or DEN2 chimeric cDNA, we were not able to clone the DEN3 C-PreM-E genes directly in the 5' intermediate vector or in the full-length chimeric DEN3-DEN4 plasmid in Escherichia coli. Nevertheless, a full-length DNA template of DEN3-DEN4 that could be used for transcription of infections RNAs was prepared by in vitro ligation. Progeny virus recovered from RNA-transfected C6/36 mosquito cells exhibited DEN3 antigenic specificity as determined by a reaction with monoclonal antibodies. Gel electrophoresis of virus-infected cell lysates yielded the predicted viral protein pattern, i.e., DEN3 C, PreM, and E and DEN4 nonstructural proteins. Two amino acid substitutions, Thr-435-->Leu and Glu-406-->Lys, which are analogous to mutations that, respectively, confer mouse neurovirulence on DEN4 and DEN2, were introduced into DEN3 E. A mutant chimera containing the Thr-435-->Leu substitution, which ablates the potential glycosylation site sequence, produced an E protein identical in size to that of wild-type DEN3 E, indicating that the glycosylation site is normally not used. Intracerebral inoculation of suckling mice revealed that the mutant chimera containing the Glu-406-->Lys substitution was neurovirulent, whereas its wild-type counterpart or parent DEN3 was not.

Animals↗
PubMed1995

Asthma in Jemez Pueblo schoolchildren.

Asthma, a major chronic health problem of children, has received little investigation in Native Americans. We conducted a survey of asthma in children of Jemez Pueblo, Jemez, New Mexico, in response to concerns of the community and health care providers about the frequency of asthma. In collaboration with Jemez Pueblo, we developed a standardized questionnaire and administered it to parents of 318 children aged 3 to 13 years. Parents reported that 12.3% had been diagnosed as having asthma or reactive airway disease by a physician or other health care practitioner. Asthma was reported as still active at the time of the interview for 55% of those subjects. The study showed that asthma was not uncommon among the Jemez Pueblo children and, in fact, was more common than in recent nationwide surveys.

Adolescent↗
PubMed1995

Suicidal thought and self-transcendence in older adults.

1. The suicide rate for adults over 65 years of age is the highest rate for suicide in any age group, and the rate is projected to increase. 2. To address a clinical concern, such as suicide, clinicians and researchers must identify factors that are specific to each population at high risk. This study chose to examine self-transcendence, which is thought to be specific to older adults' success in meeting the multiple changes of later life. 3. Two questions that address self-transcendence are: "Who is most meaningful (important) to you now?" and "What is most meaningful (important) to you now?" If an older adult is unable to answer these questions, a suicide risk assessment should probably be done.

Adaptation, Psychological↗
PubMed1995

Generation of a human monoclonal antibody to hepatitis C virus, JRA1 by activation of peripheral blood lymphocytes and hypo-osmolar electrofusion.

We have generated a human monoclonal antibody with binding specificity for hepatitis C virus (HCV)-specific peptides using peripheral blood lymphocytes isolated from a HCV antibody positive patient. The B-lymphocytes were stimulated with lipopolysaccharide (LPS) for 72 hours prior to the fusion. A recently described high efficiency hypo-osmolar electrofusion technique was employed, allowing generation of a large number of human hybridomas. The hybridomas were screened for human immunoglobulin and HCV-specific peptide binding by EIA. A single HCV-positive clone, JRA1, was detected and sub-cloned. Isotype analysis showed it to secrete an IgM lambda monoclonal antibody. The antibody was positive on both first and second generation HCV antibody analysis. This study confirms that viable pathogen-specific B-cells may be recovered from the peripheral blood. Although such cells are likely to be relatively uncommon in the circulating B-cell pool, they may be successfully immortalized by high efficiency electrofusion techniques. This technique might be valuable for the generation of human monoclonal antibodies with specificity for other human pathogens.

Adult↗
PubMed1994

Nucleosome positioning on chicken and human globin gene promoters in vitro. Novel mapping techniques.

We have developed two new techniques to assess the positions adopted by core histone octamers when reconstituted onto DNA. These, together with a previously described technique, were applied to mapping binding sites on plasmid DNAs containing either the human zeta-globin or chicken beta-globin gene promoters. Each of the approaches enabled the sites occupied by histone octamers to be measured at high resolution and, in qualitative terms, revealed the same pattern of multiple, overlapping sites. Monomer extension, one of the novel techniques, can be used to reveal binding sites over extensive stretches of a single reconstitute (approximately 1000 bp). We found the distribution of histone octamer binding sites to be largely independent of the conditions employed for reconstitution, the topology of the DNA substrate and prolonged incubation under various post-reconstitution conditions. These properties, and features of the binding site maps that we derived, suggest that histone octamer positioning on these DNAs is predominantly a characteristic of the DNA sequence itself and, by implication, that nucleosome-nucleosome interactions and the formation of nucleosome arrays are of minor influence. Some of the techniques provide quantitative information concerning the relative binding strengths of the core histone octamer for different positioning sequences. In this context, it is notable that the majority of potential binding sites compete very poorly for the histone octamer, demonstrating that under the conditions pertinent to our analysis, the range of binding strengths exhibited by the octamer for particular DNA sequences is extensive, and greater than that observed when competitive binding has been studied by methods that do not reflect precise positioning.

Animals↗
PubMed1994

Agency in health care with an endogenous budget constraint.

In this paper a doctor acts as a perfect agent for a group of patients in an environment where the health service is funded by a group of contributors. The contributor group donates resources to the health sector in accordance with its split preferences about the health care services which they would like for themselves and those which they would like for others. We show that the size of the health budget is endogenous and depends on the choices made by the doctor. The focus is on the division of the budget between health enhancing and non-health enhancing health care.

Budgets↗
PubMed1994

Axial length biometry in infants with retinopathy of prematurity.

Ultrasound axial length measurements were obtained on infants under a birthweight of 1500 g or 32 weeks gestation undergoing screening for retinopathy of prematurity (ROP). A total of 496 readings were obtained on 171 infants between 32 and 41 weeks post-conceptual age. Other details recorded were maximum stage of acute ROP, birthweight, gestational age, sex, and biparietal and occipitofrontal head diameters. The relationship of these variables to axial growth of the eye was examined using analysis of covariance with a repeated measures approach. Mean axial length increased from 15.27 mm to 16.65 mm in the left eye during this period. Following adjustment for repeated readings a growth rate of 0.18 mm/week was obtained for both eyes. Male infants were found to have longer axial lengths despite correction for birthweight, gestation and head size (p < 0.0001 right and left). Higher stages of acute ROP were also associated with shorter axial length (p < 0.05 for all stages of both eyes) but the rate of growth during the study period did not demonstrate significant differences between stages. Stage 3 infants reaching the threshold for cryotherapy had shorter axial length than stage 3 infants not receiving treatment. The effect of prematurity on the growth of the eye and the significance of these findings with respect to the subsequent development of refractive errors in premature infants are discussed.

Analysis of Variance↗