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Biomedical subjects

G DuVal

Publications and source records attributed to G DuVal.

11 recordsLinked to original sources
PubMed2005

How physicians face ethical difficulties: a qualitative analysis.

BACKGROUND: Physicians face ethical difficulties daily, yet they seek ethics consultation infrequently. To date, no systematic data have been collected on the strategies they use to resolve such difficulties when they do so without the help of ethics consultation. Thus, our understanding of ethical decision making in day to day medical practice is poor. We report findings from the qualitative analysis of 310 ethically difficult situations described to us by physicians who encountered them in their practice. When facing such situations, the physicians sought to avoid conflict, obtain assistance, and protect the integrity of their conscience and reputation, as well as the integrity of the group of people who participated in the decisions. These goals could conflict with each other, or with ethical goals, in problematic ways. Being aware of these potentially conflicting goals may help physicians to resolve ethical difficulties more effectively. This awareness should also contribute to informing the practice of ethics consultation. OBJECTIVE: To identify strategies used by physicians in dealing with ethical difficulties in their practice. DESIGN, SETTING, AND PARTICIPANTS: National survey of internists, oncologists, and intensive care specialists by computer assisted telephone interviews (n = 344, response rate = 64%). As part of this survey, we asked physicians to tell us about a recent ethical dilemma they had encountered in their medical practice. Transcripts of their open-ended responses were analysed using coding and analytical elements of the grounded theory approach. MAIN MEASUREMENTS: Strategies and approaches reported by respondents as part of their account of a recent ethical difficulty they had encountered in their practice. RESULTS: When faced with ethical difficulties, the physicians avoided conflict and looked for assistance, which contributed to protecting, or attempting to protect, the integrity of their conscience and reputation, as well as the integrity of the group of people who participated in the decisions. These efforts sometimes reinforced ethical goals, such as following patients' wishes or their best interests, but they sometimes competed with them. The goals of avoiding conflict, obtaining assistance, and protecting the respondent's integrity and that of the group of decision makers could also compete with each other. CONCLUSION: In resolving ethical difficulties in medical practice, internists entertained competing goals that they did not always successfully achieve. Additionally, the means employed were not always the most likely to achieve those aims. Understanding these aspects of ethical decision making in medical practice is important both for physicians themselves as they struggle with ethical difficulties and for the ethics consultants who wish to help them in this process.

Adult↗
PubMed2004

Institutional ethics review of clinical study agreements.

Clinical Study Agreements (CSAs) can have profound effects both on the protection of human subjects and on the independence of investigators to conduct research with scientific integrity. Sponsors, institutions, and even investigators may fail to give adequate attention to these issues in the negotiation of CSAs. Despite the key role of CSAs in structuring ethically important aspects of research, they remain largely unregulated and unreviewed for adherence to ethical norms. Academic institutions routinely enter into research contracts that fail to meet adequate ethical standards. This is a failing that can have serious consequences. Accordingly, it is necessary that some independent body have the authority both to review research contracts for compliance with norms of subject protection and ethical integrity, and to reject studies that fail to meet ethical standards. Such review should take place prior to the start of research, not later. Because of its expertise and authority, the institutional ethics review board (IRB or REB) is the appropriate body to undertake such review. Much recent commentary has focused on contractual restrictions on the investigator's freedom to publish research findings. The Olivieri experience, and that of other investigators, has brought freedom of publication issues into sharp focus. Clinical study agreements also raise a number of other ethical issues relating to human subjects and research integrity, however, including disclosures relating to patient safety, data analysis and reporting, budget, confidentiality, and premature termination of the study. This paper describes the ethical issues at stake in structuring such agreements and suggests ethical standards to guide institutional ethics review.

Bioethical Issues↗
PubMed2001

What triggers requests for ethics consultations?

OBJECTIVES: While clinical practice is complicated by many ethical dilemmas, clinicians do not often request ethics consultations. We therefore investigated what triggers clinicians' requests for ethics consultation. DESIGN: Cross-sectional telephone survey. SETTING: Internal medicine practices throughout the United States. PARTICIPANTS: Randomly selected physicians practising in internal medicine, oncology and critical care. MAIN MEASUREMENTS: Socio-demographic characteristics, training in medicine and ethics, and practice characteristics; types of ethical problems that prompt requests for consultation, and factors triggering consultation requests. RESULTS: One hundred and ninety of 344 responding physicians (55%) reported requesting ethics consultations. Physicians most commonly reported requesting ethics consultations for ethical dilemmas related to end-of-life decision making, patient autonomy issues, and conflict. The most common triggers that led to consultation requests were: 1) wanting help resolving a conflict; 2) wanting assistance interacting with a difficult family, patient, or surrogate; 3) wanting help making a decision or planning care, and 4) emotional triggers. Physicians who were ethnically in the minority, practised in communities under 500,000 population, or who were trained in the US were more likely to request consultations prompted by conflict. CONCLUSIONS: Conflicts and other emotionally charged concerns triggers consultation requests more commonly than other cognitively based concerns. Ethicists need to be prepared to mediate conflicts and handle sometimes difficult emotional situations when consulting. The data suggest that ethics consultants might serve clinicians well by consulting on a more proactive basis to avoid conflicts and by educating clinicians to develop mediation skills.

Attitude of Health Personnel↗
PubMed1991

Effects of lead on the kidney: roles of high-affinity lead-binding proteins.

Lead-induced nephropathy produces both tubular and interstitial manifestations of cell injury, but the pathophysiology of these lesions is not completely understood. Delineation of the molecular factors underlying renal handling of lead is one of central importance in understanding the mechanisms of renal cell injury from this agent. Recent studies from this laboratory have identified several distinct high-affinity lead-binding proteins (PbBP) from rat kidney and brain that appear to play critical roles in the intracellular bioavailability of lead to several essential cellular processes in these target tissues at low dose levels. The PbBP from rat kidney has been shown to be a specific cleavage product of alpha 2-microglobulin, which is a member of the retinol-binding protein superfamily. Recent preliminary Western blot and immunohistochemical studies have shown that a polyclonal antibody to the renal PbBP does not recognize the brain PbBP, which appears to be a chemically similar, but distinct molecule. These studies have also shown that the renal PbBP is selectively localized in only certain nephrons and only specific segments of the renal proximal tubule. The striking nephror and cell-type specificity of the localization reaction could result from physiological differences in nephron functional activity or selective molecular uptake mechanisms/metabolism differences that act to define target cell populations in the kidney. In addition, other preliminary studies have shown that short-term, high-dose lead exposure produces increased excretion of this protein into the urine with concomitant decreases in renal concentrations.

Alpha-Globulins↗
PubMed1989

Preliminary purification and characterization studies of a low molecular weight, high affinity cytosolic lead-binding protein in rat brain.

Carrier-free 203Pb has been used to label high affinity lead-binding proteins in rat brain cytosol to allow their initial characterization. The low molecular weight 203Pb-protein complex collected from a Sephadex G-75 column eluate has been further purified by Sephadex DEAE chromatography and then partially characterized. The protein has a molecular weight of 23,000 daltons as determined by SDS polyacrylamide gel electrophoresis and significant levels of glutamic acid (9.3%), aspartic acid (10.8%) and cysteine (9.4%). Western blot studies conducted using the polyclonal antibody to the renal lead-binding proteins showed a lack of reactivity, indicating that the brain protein is immunologically distinct from that found in the kidney.

Animals↗
PubMed1985

Some kinetic characteristics of immobilized protomers and native dimers of mitochondrial malate dehydrogenase: an examination of the enzyme mechanism.

Some kinetic characteristics of immobilized native mitochondrial malate dehydrogenase dimers and immobilized protomers, prepared by direct immobilization under conditions yielding complete dissociation without substantial unfolding, were compared to those of native soluble enzyme. Enzyme was covalently immobilized to derivatized porous glass by using a technique which permitted subsequent release of bound enzyme with 0.2 M hydroxylamine at room temperature and pH 7. Kinetic properties of enzyme released from both immobilized dimers and protomers were the same as those for native soluble enzyme, indicating that the immobilization reaction per se did not affect the structure. Both immobilized native dimers and the immobilized protomers exhibited activity with a pH dependence similar to that of native soluble enzyme. The effects of diffusional inhibition were demonstrated for both forms of the immobilized enzyme, especially for the NADH----NAD+ reaction direction. Intrinsic Michaelis constants of both immobilized forms, obtained by extrapolation of apparent values, were similar to those of the soluble enzyme. Furthermore, the effects of inhibitors and effectors with the immobilized forms were the same as those with native soluble enzyme. For example, substrate inhibition was observed with oxalacetate, the inhibitor hydroxymalonate was competitive with ketomalonate and uncompetitive with L-malate, and inhibition was observed with citrate in the NADH----NAD+ direction. Thus, immobilization did not appear to suppress the conformational equilibria of either protomers or dimers. More significantly, the kinetic characteristics of the immobilized protomer were indistinguishable from those of the dimer. Hence, a reciprocating mechanism involving subunit interactions cannot be invoked to explain the allosteric behavior of this dimeric enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Lead in detectable amounts was not observed in ocular fluids or the crystalline lens.

An earlier report described the presence of high concentrations of lead in the bovine eye. However, we have been unable to detect this heavy metal in the ocular fluids or lenses of rabbits dosed with Pb, despite the appearance of high concentrations in blood, liver, and brain. We were also unable to detect it in lenses from cattle, horses, dogs, or four elderly humans. The possibility of environmental lead exerting toxic effects in the eye thus appears to be minimal.

Aged↗
PubMed1984

Preparation and characterization of thionyl chloride-activated succinamidopropyl-glass as a covalent immobilization matrix.

The reaction of succinamidopropyl-glass with nonaqueous thionyl chloride followed by washing with water produces an activated surface which reacts with amino and thiol groups under nondenaturing conditions. Subsequent treatment of the covalently immobilized species with dilute hydroxylamine at pH 7 and room temperature releases about 80% of those molecules attached through amino groups and about 50% of those attached through thiol groups. The succinamidopropyl group appears to be a minimum requirement for such surface reactivity. The derivatized glass beads are stable during storage, and immobilization is achieved by simply contacting the surface with a solution of the protein or biochemical species to be attached. Moreover, the activated succinamidopropyl sites can be dispersed within an inert surface of glycerolpropyl sites. Such dispersion improves the subsequent release of immobilized protein and should provide a useful technique for preparation of a wide variety of specific matrices for affinity chromatography. It was possible to obtain, in solution, molecules which had been refolded from a completely denatured state in an immobilized form; however, extensive unfolding of proteins in strong denaturants reduced by roughly 50% the amount of protein which could be subsequently released.

Binding Sites↗