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Biomedical subjects

M Parker

Publications and source records attributed to M Parker.

At least 55 records · Page 3Linked to original sources

Genetics and the interpersonal elaboration of ethics.

Confidentiality in genetic testing poses important ethical challenges to the current primacy of respect for autonomy and patient choice in health care. It also presents a challenge to approaches to decision-making emphasising the ethical importance of the consequences of health care decisions. In this paper a case is described in which respect for confidentiality calls both for disclosure and non-disclosure, and in which respect for patient autonomy and the demand to avoid causing harm each appear to call both for testing without consent, and testing only with consent. This creates problems not only for clinicians, families and patients, but also for those who propose clinical bioethics as a tool for the resolution of such dilemmas. In this paper I propose some practical ways in which ethical issues in clinical genetics and elsewhere, might be addressed. In particular I call for a closer relationship between ethics and communication in health care decision-making and describe an approach to the ethics consultation that places particular emphasis on the value of interpersonal deliberation in the search for moral understanding. I reach these conclusions through an analysis of the concept of 'moral development' in which I argue that the achievement of moral understanding is a necessarily intersubjective project elaborated by moral persons.

Bioethics↗

The ethics of evidence-based patient choice.

In this paper I analyse the ethical implications of the concept of 'evidence-based patient choice' in the light of criticism of the 'individualism' of patient-centred medicine. I argue that individualism in the sense used by the critics of patient centred medicine is not an inevitable consequence of an emphasis on patient choice and that a concern with the promotion of individual choices is not incompatible with 'communitarian' values. Indeed, I argue that any ethical approach to decision-making in health-care must be capable of taking seriously both the moral status of the individual (and of his or her choices) and the moral significance of the social dimensions of such choices. The best way to ensure respect for the principle of autonomy, I suggest, is to facilitate and encourage social interactions of a particular, deliberative, kind. This is also the best way to ensure that the broader public interest is taken into account in decision-making.

Decision Making↗

Study of Medicare beneficiary complaint procedures.

New procedures for reviewing a sample of Medicare beneficiary complaints about quality of care are compared with traditional procedures at a peer review organization (PRO) for 1998-1999. These new procedures included: (1) expanded communications with complainants and providers, (2) changed data collection methods, (3) integrated concurrent review findings from other agencies, (4) expedited review procedures, and (5) changed the medical review procedures. The findings showed improved beneficiary satisfaction with the new procedures over the traditional procedures and shorter time periods for processing the reviews. Even with the new procedures, beneficiaries continued to be concerned that the review time frames were too lengthy, the reviews generally failed to confirm their complaints, and the PROs generally did not disclose the findings to the beneficiaries.

Aged↗

Pea legumin overexpressed in wheat endosperm assembles into an ordered paracrystalline matrix.

Legumin, a major component of pea seed storage vacuoles, is synthesized by a number of paralogous genes. The polypeptides are cleaved posttranslationally and can form mixed hexamers. This heterogeneity hampers structural studies, based on the production of hexamer crystals in vitro. To study a single type of homogenous legumin we produced pea legumin A in transgenic wheat (Triticum aestivum) endosperm where prolamins are predominant and only small amounts of globulins accumulate in separate inclusions. We demonstrated that the legumin precursor was cleaved posttranslationally and we confirmed assembly into 11S hexamers. Legumin was deposited within specific regions of the inclusion bodies. Angular legumin crystals extended from the inclusion bodies into the vacuole, correlating with the high legumin content. This suggests that the high-level production of a single type of legumin polypeptide resulted in the spontaneous formation of crystals in vivo. The use of a heterologous cereal system such as wheat endosperm to produce, isolate, and recrystallize homogenous 11S legume globulins offers exciting possibilities for structural analysis and characterization of these important seed storage proteins.

DNA, Complementary↗

Individual and bivalent vaccines based on alphavirus replicons protect guinea pigs against infection with Lassa and Ebola viruses.

Lassa and Ebola viruses cause acute, often fatal, hemorrhagic fever diseases, for which no effective vaccines are currently available. Although lethal human disease outbreaks have been confined so far to sub-Saharan Africa, they also pose significant epidemiological concern worldwide as demonstrated by several instances of accidental importation of the viruses into North America and Europe. In the present study, we developed experimental individual vaccines for Lassa virus and bivalent vaccines for Lassa and Ebola viruses that are based on an RNA replicon vector derived from an attenuated strain of Venezuelan equine encephalitis virus. The Lassa and Ebola virus genes were expressed from recombinant replicon RNAs that also encoded the replicase function and were capable of efficient intracellular self-amplification. For vaccinations, the recombinant replicons were incorporated into virus-like replicon particles. Guinea pigs vaccinated with particles expressing Lassa virus nucleoprotein or glycoprotein genes were protected from lethal challenge with Lassa virus. Vaccination with particles expressing Ebola virus glycoprotein gene also protected the animals from lethal challenge with Ebola virus. In order to evaluate a single vaccine protecting against both Lassa and Ebola viruses, we developed dual-expression particles that expressed glycoprotein genes of both Ebola and Lassa viruses. Vaccination of guinea pigs with either dual-expression particles or with a mixture of particles expressing Ebola and Lassa virus glycoprotein genes protected the animals against challenges with Ebola and Lassa viruses. The results showed that immune responses can be induced against multiple vaccine antigens coexpressed from an alphavirus replicon and suggested the possibility of engineering multivalent vaccines based upon alphavirus vectors for arenaviruses, filoviruses, and possibly other emerging pathogens.

Alphavirus↗

Deciding for imperilled newborns: medical authority or parental autonomy?

The ethical issues around decision making on behalf of infants have been illuminated by two empirical research studies carried out in Scotland. In-depth interviews with 176 medical and nursing staff and with 108 parents of babies for whom there was discussion of treatment withholding/withdrawal, generated a wealth of data on both the decision making process and the management of cases. Both staff and parents believe that parents should be involved in treatment limitation decisions on behalf of their babies. However, whilst many doctors and nurses consider the ultimate responsibility too great for families to carry, the majority of parents wish to be the final arbiters. We offer explanations for the differences in perception found in the two groups. The results of these empirical studies provide both aids to ethical reflection and guidance for clinicians dealing with these vulnerable families. They demonstrate the value of empirical data in the philosophical debate.

Asphyxia Neonatorum↗

What is the role of clinical ethics support in the era of e-medicine?

The internet is becoming increasingly important in health care practice. The number of health-related web sites is rising exponentially as people seek health-related information and services to supplement traditional sources, such as their local doctor, friends, or family. The development of e-medicine poses important ethical challenges, both for health professionals and for those who provide clinical ethics support for them. This paper describes some of these challenges and explores some of the ways in which those who provide clinical ethics support might respond creatively to them. By offering ways of responding to such challenges, both electronically and face-to-face, the providers of clinical ethics support can show themselves to be an indispensable part of good quality health care provision.

Access to Information↗

Prevalence of mitochondrial DNA mutations in childhood/congenital onset non-syndromal sensorineural hearing impairment.

Genetic factors are the major causes of childhood hearing impairment. Whereas autosomal recessive mutations account for the majority of prelingual non-syndromic sensorineural hearing impairment (NSSHI), the relative contribution of mitochondrial DNA (mtDNA) mutations to childhood onset NSSHI has not been established. We screened 202 subjects with congenital/childhood onset NSSHI, consisting of 110 sporadic cases, 75 sib pairs, and 17 families with affected subjects in more than one generation, in order to determine the prevalence of mtDNA mutations associated with NSSHI.mtDNA mutations were found in three of 10 families (30%) in whom the affected members were related through the maternal lineage. One sporadic case (0.9%) was also found to have a known mtDNA mutation but none was found in the sib pairs. Although the prevalence of mtDNA mutations was low in the group as a whole (2%), we suggest that screening should be considered in cases of childhood hearing impairment when it is progressive and particularly in families where transmission is compatible with maternal inheritance.

Age of Onset↗

Intracapsular hip fracture and the region-specific loss of cortical bone: analysis by peripheral quantitative computed tomography.

Generalized bone loss within the femoral neck accounts for only 15% of the increase in intracapsular hip fracture risk between the ages of 60 and 80 years. Conventional histology has shown that there is no difference in cancellous bone area between cases of intracapsular fracture and age and sex-matched controls. Rather, a loss of cortical bone thickness and increased porosity is the key feature with the greatest change occurring in those regions maximally loaded during a fall (the inferoanterior [IA] to superoposterior [SP] axis). We have now reexamined this finding using peripheral quantitative computed tomography (pQCT) to analyze cortical and cancellous bone areas, density, and mass in a different set of ex vivo biopsy specimens from cases of intracapsular hip fracture (female, n = 16, aged 69-92 years) and postmortem specimens (female, n = 15, aged 58-95 years; male, n = 11, aged 56-86 years). Within-neck location was standardized by using locations at which the ratio of maximum to minimum external diameters was 1.4 and at more proximal locations. Cortical widths were analyzed using 72 radial profiles from the center of area of each of the gray level images using a full-width/half-maximum algorithm. In both male and female controls, cancellous bone mass increased toward the femoral head and the rate of change was gender independent. Cancellous bone mass was similar in cases and controls at all locations. Overall, cortical bone mass was significantly lower in the fracture cases (by 25%; p < 0.001) because of significant reductions in both estimated cortical area and density. These differences persisted at locations that are more proximal. The mean cortical width in the cases was significantly lower in the IA (22.2%;p = 0.002) and inferior regions (19%;p < 0.001). The SP region was the thinnest in both cases and controls. These data confirm that a key feature in the etiology of intracapsular hip fracture is the site-specific loss of cortical bone, which is concentrated in those regions maximally loaded during a fall on the greater trochanter. An important implication of this work is that the pathogenesis of bone loss leading to hip fracture must be by a mechanism that varies in its effect according to location within the femoral neck Key candidate mechanisms would include those involving locally reduced mechanical loading. This study also suggests that the development of noninvasive methodologies for analyzing the thickness and estimated densities of critical cortical regions of the femoral neck could improve detection of those at risk of hip fracture.

Aged↗

Accommodation and refractive error in children with Down syndrome: cross-sectional and longitudinal studies.

PURPOSE: To examine the relationship between defective accommodation and refractive errors in children with Down syndrome. METHODS: Children with Down syndrome aged 4 to 85 months were seen at their homes as part of an ongoing study of visual development. Seventy-five children contributed cross-sectional data and 69 children longitudinal data. Accommodation was measured using a modification of Nott dynamic retinoscopy technique, and refractive error measurements were obtained using Mohindra retinoscopy. RESULTS: Accommodation was poor, regardless of the refractive error present. The total accommodation produced by the children was related to the refractive error at the time of the test, with the degree of accommodation deficit increasing with the amount of positive refractive error. The longitudinal results showed that although children with Down syndrome did not accommodate accurately, the amount of accommodation elicited did not reflect their maximum amplitude of accommodation. Each child showed a consistent degree of underaccommodation for a given stimulus. Spectacles to correct hypermetropia did not improve the accommodative response. CONCLUSIONS: In children with Down syndrome, underaccommodation is substantial, even when there is no, or a fully corrected, refractive error. The accommodation system of children with Down syndrome may have the physical capacity to respond to a given stimulus, but the neural control of the system has an anomalous set point. Spectacles do not remedy the situation. This has important implications, especially for children in a learning environment, because near vision is consistently out of focus.

Accommodation, Ocular↗

Small bowel obstruction due to postoperative adhesions: treatment patterns and associated costs in 110 hospital admissions.

The workload and costs of the emergency admissions and treatment of adhesive small bowel obstruction (ASBO) are unclear. This review details and costs the admission workload of ASBO. All admissions over a 2-year period for ASBO at two district general hospitals were identified through ICD10 diagnostic codes. Diagnostic investigations, treatment patterns, ward stay and outcome information for admissions were detailed from clinical records to develop mean cost estimates and assess the associated workload. Of the 298 admissions identified, 188 were not due to ASBO and were excluded from analysis. Of the 110 admissions detailed, 41 (37%) were treated surgically and 69 (63%) conservatively. Most admissions occurred through general practitioner referral (86.4%) to accident and emergency (90.0%). Mean (SD) length of stay was 16.3 days (11.0 days) for surgical treatment and 7.0 days (4.6 days) for conservative treatment. In-patient mortality was 9.8% for the surgical group and 7.2% for the conservative group. Costs were based on the mean values from both centres for surgical and conservative admissions and detailed according to the cost of referral and follow-up (100.98 Pounds surgical versus 102.61 Pounds conservative), hospital ward and ICU stay (3,327.48 Pounds versus 1,267.92 Pounds), theatre time (832.32 Pounds surgical only), investigations (282.73 Pounds versus 207.33 Pounds) and drug costs (133.90 Pounds versus 28.29 Pounds). Total treatment cost per admission for ASBO was 4,677.41 Pounds for surgically treated admissions and 1,606.15 Pounds for conservatively treated admissions. The impact of admissions for ASBO is considerable in terms of both costs and workload. Bed stay for these admissions represents the equivalent of almost one surgical bed per year and at least 2 days theatre time, impacting on surgical capacity and waiting lists. Adhesion prevention strategies may reduce the workload associated with ASBO. The review provides useful information for planning resource allocation.

Adolescent↗

Ethical and research dilemmas arising from a questionnaire study of psychological morbidity among general practice managers.

A questionnaire-based research project enquiring into the psychological health of general practice managers found that 5% of managers admitted to suicidal ideas. This paper explores the moral issues raised when research conducted at a distance uncovers information about participants which indicates that they may be at increased risk of harm. It examines whether the authors of such studies have responsibilities towards their research participants beyond those of analysing and properly interpreting the data supplied to them. The paper is an exercise in self-reflection and self-criticism; not all the questions posed and explored by it can be answered definitively. Implications for planning studies of this kind are discussed.

Administrative Personnel↗

Monitoring doctors' clinical competence: a Queensland focus.

The medical profession is held accountable in numerous ways, many of which are concerned with clinical competence. However, while Australia's State medical boards are statutorily charged with protecting the public from incompetent practice, they have never instituted programs aimed at maintaining the standards of all practitioners. The article describes recent legislative changes and developments in undergraduate medical education, which aim to increase physicians' accountability in relation to competence, and compares developments in Queensland and other States with those in the United Kingdom, Quebec and New Zealand. The investigation of clinical incompetence as currently undertaken by the Medical Board of Queensland should, and will, be adopted in other States. However, responding to incompetence is necessarily piecemeal, and the article further argues that the States should develop inclusive revalidation strategies. Both the community and leading voices within the profession are demanding greater commitment to a self-regulation culture that is more transparent and has sharper teeth.

Clinical Competence↗

Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus.

RNA replicons derived from an attenuated strain of Venezuelan equine encephalitis virus (VEE), an alphavirus, were configured as candidate vaccines for Ebola hemorrhagic fever. The Ebola nucleoprotein (NP) or glycoprotein (GP) genes were introduced into the VEE RNA downstream from the VEE 26S promoter in place of the VEE structural protein genes. The resulting recombinant replicons, expressing the NP or GP genes, were packaged into VEE replicon particles (NP-VRP and GP-VRP, respectively) using a bipartite helper system that provided the VEE structural proteins in trans and prevented the regeneration of replication-competent VEE during packaging. The immunogenicity of NP-VRP and GP-VRP and their ability to protect against lethal Ebola infection were evaluated in BALB/c mice and in two strains of guinea pigs. The GP-VRP alone, or in combination with NP-VRP, protected both strains of guinea pigs and BALB/c mice, while immunization with NP-VRP alone protected BALB/c mice, but neither strain of guinea pig. Passive transfer of sera from VRP-immunized animals did not confer protection against lethal challenge. However, the complete protection achieved with active immunization with VRP, as well as the unique characteristics of the VEE replicon vector, warrant further testing of the safety and efficacy of NP-VRP and GP-VRP in primates as candidate vaccines against Ebola hemorrhagic fever.

Animals↗