Medicine for the millennium: the challenge of postmodernism.
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Humans↗
Biomedical subjects
M Parker
Publications and source records attributed to M Parker.
PEP trial. Pulmonary Embolism Prevention.
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Aspirin↗
Pegylation of magnetically oriented lipid bilayers.
We report NMR data for magnetically oriented phospholipid bilayers which have been doped with a lipid derivatized with a polyethylene glycol polymer headgroup to stabilize samples against aggregation. (13)C, (31)P, and (2)H NMR data indicate that the incorporation of PEG2000-PE (1% molar to DMPC) does not interfere with the orientation properties of bicelles prepared at 25% w/v with or without the presence of lanthanide. Bicelles prepared at 10% w/v are also shown to orient when PEG2000-PE is added. The addition of PEG2000-PE to cholesterol-containing, lanthanide-flipped bicelles is shown to inhibit sample phase separation and improve spectral quality. Furthermore, the addition of PEG2000-PE to high w/v bicelles (40% w/v) is demonstrated to lead to an increase in overall sample order.
Cholesterol↗
The nuclear receptor co-repressor nrip1 (RIP140) is essential for female fertility.
Ovulatory dysfunction is the commonest cause of female infertility. Here we show that the co-repressor nuclear-receptor-interacting protein 1 (Nrip1; encoded by the gene Nrip1) is essential for ovulation. Mice null for this protein are viable, but female mice are infertile because of complete failure of mature follicles to release the oocyte at ovulation. In contrast, luteinization proceeds normally, resulting in a phenotype closely resembling that of luteinized unruptured follicle syndrome, often associated with infertility in women. Therefore, whereas the pre-ovulatory surge of luteinizing hormone induces both ovulation and luteinization, the ability to suppress the action of nuclear receptors is essential for the coordinated control of ovarian function with the essential process of oocyte release dependent on the activity of the transcriptional co-repressor Nrip1 (RIP40).
Adaptor Proteins, Signal Transducing↗
Medical ethics in the 21st century.
OBJECTIVES: To foresee how medical ethics may develop in the 21st century. DESIGN: We have looked into our crystal ball to see what factors are likely to drive medical ethics over the next few decades. We have given examples of how such factors might affect specific issues. RESULTS: Those factors that we identified as likely to shape the future of medical ethics are: Globalization: Medical ethics is likely to have to grapple increasingly with ethical issues arising from the huge discrepancies in the level of health care available in different countries. Increase in longevity: We predict that there will be, at least amongst the richer nations, a significant increase in life expectancy. This will result in issues of resource allocation becoming increasingly problematic within medicine. Child enhancement: Developments in genetics combined with control of reproduction will make it possible to select our children for a broad range of characteristics. There are optimistic and pessimistic predictions as to how such power will be used. In either case, this area will be an important focus of concern in medical ethics. The biological determination of behaviour: Genetic research will lead to an increasing sense that undesirable behaviour is genetically determined. This will lead to a re-examination of such concepts as criminal responsibility. Therapeutic research and clinical practice: We predict that an increasing amount of clinical practice will be within the setting of clinical trials. The ethics of therapeutic research and clinical practice will need to be brought within a coherent framework.
Clinical Medicine↗
Medicine, psychiatry and euthanasia: an argument against mandatory psychiatric review.
OBJECTIVE: The paper critically appraises the argument that requests for active assistance to die should be subject to mandatory psychiatric assessment. METHOD: The argument for mandatory psychiatric assessment is usually supported by an appeal to the need for safeguards against errors and omissions in both the diagnosis of psychiatric conditions affecting the terminally ill and the exploration of the meanings of their requests. This intuitively appealing view is challenged through a broader analysis which examines connections between medicine's traditional adherence to the moral distinction between acts and omissions and the following issues: the historical relationship between medical practice and dying, the recent development of research into treatment-withdrawal decisions, the scientific status of psychiatry, the logic of rationality and decision-making competence. RESULTS: The analysis reveals a number of hitherto unexamined and unacknowledged influences which would make psychiatric review of requests for assisted death a much less objective and impartial process than is assumed. CONCLUSION: Mandatory psychiatric review is an instance of the medicalisation of death and dying which could abridge the freedom of certain individuals to make decisions about their deaths.
Attitude to Death↗
Building community in the healthcare workplace. Part 2, Envisioning the reality.
Squeezed between mounting budget pressures and staffing demands, healthcare managers have little room to maneuver as they are buffeted by incessant new strategies. So what is the constant that they can use to keep a steady course through all the chaos? We suggest that the overarching constant is "community in the workplace." Although community building may have both short- and long-term benefits, it is not a strategy but a career-long philosophy, structure, and approach to help managers tie together all the facets of their daily work into a more meaningful and satisfying purpose. This article, part 2 in a 4-part series, explores the principles and characteristics of community and provides material for further study and discussion. Four conceptual cornerstones--philosophy, influence, culture, and inner transformation--are considered in relation to the community approach. Part 1 (April) described the negative dynamics that obstruct sustainable change and reasons for moving to community at work. Part 3 (October) will describe how to build community and will give options for implementing change in complex adaptive systems. The final article (November) presents case studies and discusses how community can be built in a unionized environment.
Communication↗
Building community in the healthcare workplace, Part 3: Belonging and satisfaction at work.
Squeezed between mounting budget pressures and staffing demands, healthcare managers have little room to maneuver as they are buffeted by incessant new strategies. So what is the constant that they can use to keep a steady course through all the chaos? We suggest the overarching constant is "community in the workplace." Although community building may have both short- and long-term benefits, it is not a strategy but a career-long philosophy to help managers tie together all the facets of their daily work into a more meaningful and satisfying purpose. This article, part 3 in a 4-part series, describes methods for building community in the entire organization or in a single unit. Options for implementing change in complex adaptive systems such as hospitals are discussed, along with remedies for the most common obstacles managers will encounter. Part 1 (July/August) described the negative dynamics that obstruct sustainable change and reasons for moving to community at work. Part 2 (September) discussed the basic characteristics and principles of community building. The final article (November) will present a case study and will discuss how community can be built in a unionized environment.
Humans↗
Building community in the healthcare workplace, Part 4. Partnering with union members to create community.
Squeezed between mounting budget pressures and staffing demands, healthcare managers have little room to maneuver as they are buffeted by incessant new strategies. So what is the constant that they can use to keep a steady course through all the chaos? We suggest the overarching constant is "community in the workplace." Although community building may have both short- and long-term benefits, it is not a strategy but a career-long philosophy to help managers tie together all the facets of their daily work into a more meaningful and satisfying purpose. This article, part 4 in a 4-part series, discusses partnering with union leaders and members to create a sense of community in the organization. Using a case study of an organization that had significant success implementing the community philosophy, this article describes concepts, structures, and processes that work, and a few that do not, in a unionized environment. Part 1 (July/August) described the negative dynamics that obstruct sustainable change and reasons for moving to community at work. Part 2 (September) discussed the basic characteristics and principles of community building. Part 3 (October) illustrated community implementation options and obstacles.
Humans↗
Public deliberation and private choice in genetics and reproduction.
The development of human genetics raises a wide range of important ethical questions for us all. The interpersonal dimension of genetic information in particular means that genetics also poses important challenges to the idea of patient-centredness and autonomy in medicine. How ought practical ethical decisions about the new genetics be made given that we appear, moreover, no longer to be able to appeal to unquestioned traditions and widely shared communitarian values? This paper argues that any coherent ethical approach to these questions must be able both to uphold the moral status of the individual and at the same time recognise the communitarian, interpersonal dimensions both of the world in which we live and of personal autonomy itself. The paper then goes on to propose an approach to the resolution of the ethical questions raised by the use of the new genetics in reproductive choice through the development of a coherent and principled process of public reason and justification oriented towards the support and development of personal autonomy.
Ethics, Medical↗
The effect of age, size of target, and cognitive factors on accommodative responses of children with Down syndrome.
PURPOSE: To investigate possible factors that may be implicated in the poor accommodative responses of individuals with Down syndrome. This article evaluates the effect of age, angular size of target, and cognitive factors on accommodation. METHODS: Seventy-seven children with Down syndrome who are participating in an ongoing study of visual development were assessed. One hundred thirty-one developmentally normal children took part in a previous study and provided control data. Accommodation was measured using a modified Nott dynamic retinoscopy technique. RESULTS: Children with Down syndrome showed considerably poorer accommodative responses than normally developing children. No target used in the present study produced an improved response in children with Down syndrome. Age, angular subtense of target, and cognitive factors could not fully account for the poor accommodation in children with Down syndrome. CONCLUSIONS: Poor accommodation is a common feature of Down syndrome, regardless of the target used. The etiology of the deficit has yet to be established. It is imperative that educators and clinicians are aware that near vision is out of focus for these children.
Accommodation, Ocular↗
Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States.
In late summer 1999, an outbreak of human encephalitis occurred in the northeastern United States that was concurrent with extensive mortality in crows (Corvus species) as well as the deaths of several exotic birds at a zoological park in the same area. Complete genome sequencing of a flavivirus isolated from the brain of a dead Chilean flamingo (Phoenicopterus chilensis), together with partial sequence analysis of envelope glycoprotein (E-glycoprotein) genes amplified from several other species including mosquitoes and two fatal human cases, revealed that West Nile (WN) virus circulated in natural transmission cycles and was responsible for the human disease. Antigenic mapping with E-glycoprotein-specific monoclonal antibodies and E-glycoprotein phylogenetic analysis confirmed these viruses as WN. This North American WN virus was most closely related to a WN virus isolated from a dead goose in Israel in 1998.
Amino Acid Sequence↗
The role of coactivators in steroid hormone action.
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Animals↗
Echocardiographic prevalence of mitral and/or aortic regurgitation in patients exposed to either fenfluramine-phentermine combination or to dexfenfluramine.
We evaluated the prevalence of valvular regurgitation in patients who have taken anorectic medications. Two-dimensional echocardiograms with color flow Doppler were recorded in 200 consecutive patients referred to a major metropolitan hospital for evaluation of cardiac function because of a history of anorectic medication use. Each patient filled out a questionnaire at the time of the visit or through telephone contact. Each echocardiogram was reviewed by 2 observers. The degree of valvular regurgitation was graded by a consensus of both observers. Significant valvular regurgitation was defined as at least moderate mitral regurgitation (MR) or at least mild aortic regurgitation (AR), as recommended by the Food and Drug Administration and Centers for Disease Control and Prevention. For all patients having taken anorectic drugs, there was a 5% prevalence of at least moderate MR, a 12% prevalence of at least mild AR, and a 16% prevalence of significant MR and/or AR. Patients with significant AR and/or MR were older than those without significant valvular regurgitation (49+/-12 vs 44+/-11 years, p = 0.03). Patients with significant MR and/or AR had a longer exposure duration (8 vs 6 months, p = 0.049) to anorectic drugs. There was no difference in weight loss between those with and without significant regurgitation (p = NS). The 2 largest subgroups were patients who took the fenfluramine-phentermine combination (n = 127) and those who took dexfenfluramine alone (n = 42). The prevalence of significant MR and AR was 5% and 9% for the fenfluramine-phentermine group and 0% and 14% for the dexfenfluramine group, respectively. There was also a high subthreshold level of MR and AR in these patients.
Adult↗
Steroid and nuclear receptors. Villefranche-sur-Mer, France, May 25-27, 1999.
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Animals↗
Congenital non-syndromal sensorineural hearing impairment due to connexin 26 gene mutations--molecular and audiological findings.
We screened DNA from 72 sibships and 138 sporadically affected individuals with congenital non-syndromal sensorineural hearing impairment (NSSNHI) for mutations in the 26 (CX26) gene. A total of 20 (27.8%) of the sibships and 11 (7.9%) of the sporadically affected individuals were homozygous or compound heterozygotes for CX26 mutations. A total of 11 (17.2%) of 64 individuals with severe and 30 (30%) of 100 with profound NSSNHI compared to eight (8.7%) of 92 persons with moderate and none (0%) of 19 individuals with mild hearing impairment were homozygous or compound heterozygotes for CX26 mutations (chi2 test, 3 df, P = 0.000). CX26 mutation status bad no effect on the symmetry of the hearing impairment or configuration of the audiogram. In addition, serial audiograms showed no evidence of progression of the hearing impairment or differences in the severity of the hearing impairment in affected siblings in persons whether or not due to CX26 mutations. Sporadically affected individuals with congenital NSSNHI should be routinely tested for mutations in CX26, especially if the hearing impairment is severe or profound in severity, since identification of a mutation in CX26 allows use of Mendelian recurrence risks.
Audiometry, Pure-Tone↗
Two structural transitions in membrane pore formation by pneumolysin, the pore-forming toxin of Streptococcus pneumoniae.
The human pathogen Streptococcus pneumoniae produces soluble pneumolysin monomers that bind host cell membranes to form ring-shaped, oligomeric pores. We have determined three-dimensional structures of a helical oligomer of pneumolysin and of a membrane-bound ring form by cryo-electron microscopy. Fitting the four domains from the crystal structure of the closely related perfringolysin reveals major domain rotations during pore assembly. Oligomerization results in the expulsion of domain 3 from its original position in the monomer. However, domain 3 reassociates with the other domains in the membrane pore form. The base of domain 4 contacts the bilayer, possibly along with an extension of domain 3. These results reveal a two-stage mechanism for pore formation by the cholesterol-binding toxins.
Bacterial Proteins↗