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Biomedical subjects

D Clark

Publications and source records attributed to D Clark.

At least 55 records · Page 3Linked to original sources
PubMed2002

Palliative care and policy in England: a review of health improvement plans for 1999-2003.

Since 1987 health authorities in England have been required to make plans for palliative care provision, but their record in doing so has been patchy. The production of health improvement plans (HlmPs), in which each health authority must set out its priorities and actions designed to improve the health and well-being of its local population, provides an opportunity to examine the extent to which palliative care provision in the NHS is regarded as a priority by policy makers in England. This paper reports on a structured documentary review of the HlmPs published by the 99 health authorities in England. The review indicates that at the moment, in spite of the longstanding duty placed on health authorities to develop strategic plans for palliative care and to assess the level of local palliative care needs, not all have made significant progress in this direction. Among those that do have plans for palliative care, the vast majority of these plans are for people with cancer. What emerges most clearly is a sense in which specialist palliative care, especially for non-cancer patients, is perceived as an 'optional extra' by many health authorities rather than an integral and essential part of the overall supportive care strategy which they clearly are at pains to develop.

Community Health Planning↗
PubMed2001

Spiritual care. Soul survivors.

The importance of meeting spiritual needs when caring for older people is increasingly acknowledged. A survey of nursing and residential homes in the Trent region showed managers interpreted spiritual care very broadly, according favourite television programmes and countryside visits some spiritual significance. Most thought all home staff had a responsibility for residents' spiritual care.

Aged↗
PubMed2001

The bifunctional Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) protein is necessary for amebic growth and survival and requires an intact C-terminal domain for both alcohol dahydrogenase and acetaldehyde dehydrogenase activity.

The intestinal protozoan pathogen Entamoeba histolytica lacks mitochondria and derives energy from the fermentation of glucose to ethanol with pyruvate, acetyl enzyme Co-A, and acetaldehyde as intermediates. A key enzyme in this pathway may be the 97-kDa bifunctional E. histolytica alcohol dehydrogenase 2 (EhADH2), which possesses both alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase activity (ALDH). EhADH2 appears to be a fusion protein, with separate N-terminal ALDH and C-terminal ADH domains. Here, we demonstrate that EhADH2 expression is required for E. histolytica growth and survival. We find that a mutant EhADH2 enzyme containing the C-terminal 453 amino acids of EhADH2 has ADH activity but lacks ALDH activity. However, a mutant consisting of the N-terminal half of EhADH2 possessed no ADH or ALDH activity. Alteration of a single histidine to arginine in the putative active site of the ADH domain eliminates both ADH and ALDH activity, and this mutant EhADH2 can serve as a dominant negative, eliminating both ADH and ALDH activity when co-expressed with wild-type EhADH2 in Escherichia coli. These data indicate that EhADH2 enzyme is required for E. histolytica growth and survival and that the C-terminal ADH domain of the enzyme functions as a separate entity. However, ALDH activity requires residues in both the N- and C-terminal halves of the molecule.

Alcohol Dehydrogenase↗
PubMed2001

Siloxane-based biocatalytic films and paints for use as reactive coatings.

We have developed a new methodology for preparing films and paints suitable for use as biocatalytic coatings. The hydrolytic enzymes pronase and alpha-chymotrypsin were immobilized by either sol-gel entrapment or by covalent attachment into a polydimethylsiloxane (PDMS) matrix and cast into thin films or incorporated into an oil-based paint formulation. All of the coatings retained enzymatic activity and adhered to several different materials. The enzymatic films and paints also exhibited higher thermostability than enzyme free in solution or covalently attached to the outer surface of PDMS. A porous membrane based on a PDMS-immobilized enzyme was also prepared by an immersion precipitation process. Protein adsorption measurements showed that the enzyme-containing films and paints adsorbed less protein than enzyme-free controls, and that protein adsorption decreased with increasing proteolytic activity of the coating. These coatings thus provide the means to apply a stable enzymatic surface to a wide range of materials, and may be generally useful as biocatalytic paints and films.

Adsorption↗
PubMed2001

Significance of p53 mutations in patients with chronic lymphocytic leukemia: a sequential study of 30 patients.

BACKGROUND: In patients with B-cell chronic lymphocytic leukemia (CLL), considerable disease heterogeneity within clinical stages necessitates the search for relevant prognostic indicators, particularly those that may help to determine the need for early therapeutic intervention. In the current study, the authors investigated the role of p53 mutations and chromosomal abnormalities in 30 patients with CLL. METHODS: Thirty patients were screened for p53 mutations. Half of the group had aggressive disease characterized by leucocytosis, lymph node enlargement, organomegaly, and shortened tumor doubling time. Because 95% of p53 mutations reside in "hot-spot" regions of exons 5-9 of the p53 gene, the authors sequenced these exons completely for mutation detection. RESULTS: Sequence analysis identified p53 mutations in 14 of 30 patients that were distributed equally among patients with aggressive disease and nonaggressive disease. There were six mutations in exon 7, five mutations in exon 5, and one mutation each in exons 6 and 8. Five of 15 patients with clinically aggressive disease had mutations in exon 7. Only one patient with nonaggressive disease had an exon 7 mutation. Abnormal cytogenetics were present in 22 of 30 patients (73%). Most patients with the p53 mutation (13 of 14 patients; 93%) displayed abnormal cytogenetics. Twelve of 15 patients with aggressive disease and 9 of 15 patients with average disease exhibited abnormal karyotypes. CONCLUSIONS: The presence of p53 mutations did not predict clinical behavior or disease outcome, although the frequency of mutations appears to be higher than reported previously. In this study, mutations of exon 7 (5 of 6 patients) occurred in patients with clinically aggressive disease. The significance of this observation warrants further examination.

Exons↗
PubMed2001

An enantioselective synthesis of insecticidal 4-alkynyloxazolines.

2-(2,6-Difluorophenyl)-4-phenylalkynyl oxazolines are potent insect growth regulators. An efficient and enantioselective synthesis to these compounds has been developed which relies on a (-)-sparteine mediated hydroxymethylation of the lithium dianion of propargylic amides.

Alkynes↗
PubMed2001

Biochemical and immunological properties of human cardiac troponin I fragments.

Cardiac troponin I (cTnI) is the inhibitory subunit of the troponin complex and is a biochemical marker for myocardial infarction (MI). It is found in human serum within 4-6 h following MI. One of us has shown [Morjana (1998) Biotechnol. Appl. Biochem. 28, 105-111] that MI patient serum TnI is cleaved at the N- and C-terminals and that the TnI fragments exist as a complex with tropinin C (TnC) and troponin T (TnT). In the present study, we have generated C-terminal truncated TnI fragments and studied their immunological and biochemical properties. Human recombinant TnI (rTnI) expressed in Escherichia coli is cleaved into a major fragment with a molecular mass of 17500 Da using CNBr. The major CNBr fragment contains the first 153 amino acids of human cTnI (TnI153). Cleavage of the rTnI with the endoproteinase Asp-N generates a smaller TnI fragment (TnI88, residues 6-96). TnI153 has higher immunological activity than that of rTnI and lower activity than that of TnI88, as judged by the Stratus II TnI Immunoassay. TnI153 exhibits biochemical and immunological properties similar to those of intact TnI. It binds TnC at a molar ratio of 1:1 and forms a ternary complex with TnC and TnT. TnC enhances the immunological activity of TnI153, but has little effect on the activity of TnI88. The TnI153-TnC complex exhibits higher immunological activity than rTnI-TnC and TnI88-TnC, and much higher activity than free rTnI, TnI153 and TnI88. The presence of TnT has no effect on the immunological activity of the TnI153-TnC complex, suggesting that the addition of TnT does not interfere with TnI153 recognition by TnI monoclonal antibodies. Free TnI153 and TnI88 degrade rapidly in human serum. TnC protects TnI153 from proteolytic degradation, but offers less protection for TnI88. The TnI88-TnC complex lost 80% of its immunological activity after incubation for 2 days in human serum at 37 degrees C. However, there was no loss in the immunological activity of the TnI153-TnC complex under the same conditions. A cTnI fragment (TnI80, residues 1-80), expressed in E. coli as a fusion protein, exhibits immunological activity and stability similar to that of TnI88.

Biomarkers↗
PubMed2001

Angina pectoris and coronary artery disease in severe isolated valvular aortic stenosis.

BACKGROUND: Angina pectoris has long been recognised as one of the principal symptoms of severe aortic valve stenosis (AS), even in patients without significant coronary artery disease (CAD). However, controversy exists concerning the prevalence of angina pectoris and associated CAD in such patients. OBJECTIVE: To determine the prevalence of CAD detectable by angiography and its relation to angina pectoris and coronary risk factors in patients with severe AS. PATIENTS AND METHODS: All patients with symptomatic AS who had undergone aortic valve replacement and preoperative cardiac catheterisation at the Austin and Repatriation Medical Centre between 1 January 1986 and 31 May 1996 were retrospectively analysed. Those patients with multiple valve disease, aortic regurgitation of grade 2 or more in severity, or who had had prior coronary artery or valve surgery were excluded from this analysis. RESULTS: A total of 328 consecutive patients with severe AS (242 men and 86 women; mean age 72 years, range 39-84 years) were studied. Significant CAD (reduction in luminal diameter > or = 50%) was found in 162 patients (49.4%). Typical angina was present in 74.7% of these 162 patients but it was also found in 44.6% of the 166 patients without obstructive CAD. Of the patients without angina (n = 133), 30.8% had significant CAD. By multivariate logistic regression, we have identified seven significant predictors for CAD among severe AS patients. Five factors increased risk. Expressed as odds ratio with 95% confidence interval, these included: (i) age in years (1.07; 1.04-1.11, P = 0.001); (ii) male gender (2.09; 1.14-3.80, P = 0.016); (iii) angina pectoris (3.19; 1.89-5.37, P < 0.001); (iv) history of myocardial infarction (2.87; 1.38-5.97, P = 0.005); and (v) peripheral vascular disease (2.28; 1.28-4.05, P = 0.005). Factors associated with decreased likelihood of CAD were serum high density lipoprotein (HDL) cholesterol (0.58; 0.34-0.71, P = 0.002) and peak systolic gradient across the aortic valve (0.97; 0.95-0.99, P = 0.0113). CONCLUSION: Coronary arteriography can probably be omitted for a patient with severe AS if that patient has no symptoms of angina and has no risk factors known to increase its incidence.

Journal Article↗
PubMed2001

Religion, medicine, and community in the early origins of St. Christopher's Hospice.

Commentators on the history and development of hospice and palliative care can appear inclined toward a revisionist viewpoint that sees something "lost" in recent years from the original concept. The thesis concerning the "secularization of hospice" is one such example. It is suggested that the quality of these debates can be improved by serious scholarly attention to earlier events and circumstances, drawing on contemporary source materials, rather than retrospective viewpoints. This article, based mainly on correspondence from the early 1960s, explores ideas that shaped the early origins of St. Christopher's Hospice, England. It shows how Cicely Saunders and her associates created an Aim and Basis for the hospice that sought to reconcile questions about its religious orientation; its relationship to medicine; and its status as a community. We see how tensions between these were resolved, resulting in a model that would be applicable in other contexts. Without this pragmatic turn, it is unlikely that the hospice movement would have spread so quickly and so far in the 1970s and 1980s.

Correspondence as Topic↗
PubMed2001

UK geriatricians' attitudes to active voluntary euthanasia and physician-assisted death.

AIM: To describe the views of British geriatricians on active voluntary euthanasia and physician-assisted death. METHOD: Postal questionnaire to 742 consultant members of the British Geriatrics Society. RESULTS: 81% considered active voluntary euthanasia never to be justified ethically, although 23% supported legalization in some situations and 13% would be willing to administer active voluntary euthanasia in some situations. With regard to physician-assisted death, 68% opposed it on ethical grounds and 24% supported its legalization in some instances, with 12% stating they would be willing to provide such assistance in some situations. Free text comments frequently cited good palliative care as an important response to such issues in clinical practice.

Adult↗
PubMed2001

The predominant aciduric microflora of root-caries lesions.

The etiology of root caries is not fully understood, and although mutans streptococci, lactobacilli, and A. naeslundii have been implicated in its initiation and progression, this study was designed to determine the potential role of other microbial species and the nature of predominant aciduric microflora in the root caries process. We isolated the predominant aciduric microflora from root-caries lesions (n = 14) and sound root surfaces in subjects with (n = 13) or without (n = 10) root caries, using both a "most probable numbers" method and conventional plating methods. The predominant aciduric bacteria from root lesions were lactobacilli and A. israelii, while from sound root surfaces in subjects with root caries, A. gerencseriae comprised over 60% of aciduric isolates. Mutans streptococci were not among the aciduric isolates. Subjects without root caries harbored fewer bacteria, and S. anginosus (pH 4.8) and S. oralis (pH 5.2) were the predominant aciduric bacteria. The microbial etiology of root caries is more complex than was previously appreciated, and factors underlying the microbial succession occurring during the disease process are not known. Taxa with previously unrecognized aciduric characteristics have been isolated routinely, and the role of these organisms in the root caries process requires further investigation.

Actinomyces↗
PubMed2001

Needs assessment for palliative care: three projects compared.

Needs assessment remains an inexact yet evolving field of activity in palliative care. One reason for the variable quality of needs assessments in palliative care is the pragmatic orientation that comes from limited time and resources. Consequently a comprehensive approach to palliative care needs assessment is often not achieved. One route to its improvement lies in sharing experiences about techniques and methods in conducting needs assessment studies. In this paper we offer some thoughts on our own experience of conducting needs assessment for palliative care in three separate locations within a single English health region. We describe the context in which the projects were conducted; the background and origin of each study; the aims and methods used; the research process in each case; key findings; as well as the dissemination process and impact of the work. We show some of the different forms which palliative care needs assessment can take and conclude with some general principles intended to improve practice in this challenging area of health services research.

England↗
PubMed2001

Tending the soul as well as the body: spiritual care in nursing and residential homes.

This article reports findings from a study in the UK which investigated the perceptions and practice of spiritual care in care homes for older people. Over 1500 homes were sent a postal questionnaire and a response rate of 42% was achieved. Home managers were found to have a broad understanding of spiritual care, according a spiritual dimension to a range of tasks that were social and emotional in nature. Most managers felt that responsibility for providing spiritual care lay with the home itself, rather than other parties, although concerns were expressed over the ability of some staff to deliver this care. Many homes had input from religious providers via regular services and visiting personnel. There was a perception of a heightened level of spiritual need for dying residents, although it is suggested that physical pain continues to dominate the focus of care at this stage.

Aged↗