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Biomedical subjects

M Little

Publications and source records attributed to M Little.

At least 19 recordsLinked to original sources

'On being both professional and human': a response.

A recent publication in the Internal Medicine Journal touches on some sensitive points. It emphasizes deficiencies in communication between doctors and patients and between doctors and families of the patients, particularly in extreme medical circumstances that are likely to end in death. It stresses as well the trauma of seeing a loved one reduced from a human being with a distinctive biography to an impersonal clinical problem. Such articles have a long history but seldom produce any change in the attitudes or practices of the medical profession. There seem to be a number of reasons for this, including clinicians' ambivalence towards the real importance of ethics in medicine and the lack of a forum in which consumers and doctors might air and discuss their experiences of suffering and disappointment. A forum for mutual discussion is suggested as the most constructive step to take. Medical education has not proven to be an answer to the problems of sensitive communication.

Attitude of Health Personnel↗

A risk assessment based approach to the management of acute poisoning.

Early assessment and management of poisoning constitutes a core emergency medicine competency. Medical and psychiatric emergencies coexist; the acute poisoning is a dynamic medical illness that represents an acute exacerbation of a chronic underlying psychosocial disorder. The emergency physician must use an approach that ensures early decisions address potentially time critical interventions, while allowing management to be tailored to the individual patient's needs in that particular medical setting. This article outlines a rationale approach to the management of the poisoned patient that emphasises the importance of early risk assessment. Ideally, this approach should be used in the setting of a health system designed to optimise the medical and psychosocial care of the poisoned patient.

Antidotes↗

Toxicology case of the month: oral hypoglycaemic overdose.

A teenager ingests 375 mg of glipizide and 14.5 g of melformin intentionally in a small country town. She presents to the local medical facility with symptoms and signs of hypoglycaemia. Using a risk assessment based approach, the management of suiphonylurea and metformin overdose is discussed. Sulphonylurea overdose invariably results in profound hypoglycaemia that requires resuscitation with IV dextrose and the use of octreotide as an antidote. Metfonnin overdose rarely causes problems.

Adolescent↗

Toxicology case of the month: Carbamazepine overdose.

A 29-year-old woman presents shortly after a massive overdose of carbamazepine controlled-release tablets. In anticipation of coma, she is electively intubated to safely enable gastrointestinal decontamination with nasogastric activated charcoal. She is admitted to the intensive care unit for ongoing supportive care, and further doses of activated charcoal are prescribed to enhance elimination of carbamazepine. Carbamazepine levels remain high and haemodialysis is carried out to further enhance elimination. Her coma resolves as levels fall, but clinical progress is complicated by anticholinergic delirium, ileus and bowel obstruction from charcoal concretions. She survives to medical discharge on day 12.

Adult↗

Toxicology case of the month: ingestion of two unidentified tablets by a toddler.

An asymptomatic 18 month old child presents to the emergency department of a small district hospital shortly after ingesting two unidentified tablets. A small number of pharmaceuticals and illicit drugs may produce life threatening toxicity in a small child if ingested even in one or two dose units and the onset of toxicity may be delayed for some agents. Following risk assessment, a rational management plan is devised and the child is carefully monitored. The patient is observed overnight and discharged home the following day.

Decontamination↗

Expressing freedom and taking liberties: the paradoxes of aberrant science.

Complete freedom does not exist, despite people's preparedness to die for it. Scientific freedom is much defended and yet much misunderstood. Scientists have limits imposed on their freedom by the disciplines and discourse communities in which they place themselves. Freedom within these socially constructed constraints needs to be distinguished from taking liberties with the rules and practices that make up these constraints, and validate the activities of special groups within society. Scientists (and the public) perceive taking liberties with science's rules and practices as aberrant science, and they often react punitively. Aberrant science can be broadly examined under four headings: wicked science, naughty science, dysfunctional science, and ideologically unacceptable science. When we examine examples of perceived aberrant science, we find that these categories of "misconduct" are connected and often confused. Scientific freedom needs to be redefined with due regard to current understandings of scientists as human beings facing powerful social pressures to deliver results of a particular kind.

Attitude↗

Temporal and spatial transcriptional programs in murine kidney development.

We have performed a systematic temporal and spatial expression profiling of the developing mouse kidney using Compugen long-oligonucleotide microarrays. The activity of 18,000 genes was monitored at 24-h intervals from 10.5-day-postcoitum (dpc) metanephric mesenchyme (MM) through to neonatal kidney, and a cohort of 3,600 dynamically expressed genes was identified. Early metanephric development was further surveyed by directly comparing RNA from 10.5 vs. 11.5 vs. 13.5dpc kidneys. These data showed high concordance with the previously published dynamic profile of rat kidney development (Stuart RO, Bush KT, and Nigam SK. Proc Natl Acad Sci USA 98: 5649-5654, 2001) and our own temporal data. Cluster analyses were used to identify gene ontological terms, functional annotations, and pathways associated with temporal expression profiles. Genetic network analysis was also used to identify biological networks that have maximal transcriptional activity during early metanephric development, highlighting the involvement of proliferation and differentiation. Differential gene expression was validated using whole mount and section in situ hybridization of staged embryonic kidneys. Two spatial profiling experiments were also undertaken. MM (10.5dpc) was compared with adjacent intermediate mesenchyme to further define metanephric commitment. To define the genes involved in branching and in the induction of nephrogenesis, expression profiling was performed on ureteric bud (GFP+) FACS sorted from HoxB7-GFP transgenic mice at 15.5dpc vs. the GFP- mesenchymal derivatives. Comparisons between temporal and spatial data enhanced the ability to predict function for genes and networks. This study provides the most comprehensive temporal and spatial survey of kidney development to date, and the compilation of these transcriptional surveys provides important insights into metanephric development that can now be functionally tested.

Animals↗

From advance directives to advance care planning: current legal status, ethical rationales and a new research agenda.

This paper uses a case example to review the current legal status of advance directives, as well as their ethical rationale. We draw attention to ongoing efforts to institutionalize advance directives, and to some of the tractable and intractable reasons why advance directives are ineffective. We then introduce the concept of advance care planning, and argue that we should not assume that advance care directives have a place in this process. We conclude by offering three reasons why this assumption may operate, and by suggesting that contingency and uncertainty may sometimes overwhelm all rational approaches to medical care.

Advance Care Planning↗

Is there an Aboriginal bioethic?

It is well recognised that medicine manifests social and cultural values and that the institution of healthcare cannot be structurally disengaged from the sociopolitical processes that create such values. As with many other indigenous peoples, Aboriginal Australians have a lower heath status than the rest of the community and frequently experience the effects of prejudice and racism in many aspects of their lives. In this paper the authors highlight values and ethical convictions that may be held by Aboriginal peoples in order to explore how health practitioners can engage Aboriginal patients in a manner that is more appropriate. In doing so the authors consider how the ethics, values, and beliefs of the dominant white Australian culture have framed the treatment and delivery of services that Aboriginal people receive, and whether sufficient effort has been made to understand or acknowledge the different ethical predispositions that form the traditions and identity of Aboriginal Australia(ns).

Australia↗

The Wilms' tumour suppressor protein, WT1, undergoes CRM1-independent nucleocytoplasmic shuttling.

The Wilms' tumour suppressor gene (WT1) encodes a zinc finger-containing nuclear protein essential for kidney and urogenital development. Initially considered a transcription factor, there is mounting evidence that WT1 has a role in post-transcriptional processing. Using the interspecies heterokaryon assay, we have demonstrated that WT1 can undergo nucleocytoplasmic shuttling. We have also mapped the region responsible for nuclear export to residues 182-324. Our data add further complexity to the role of WT1 in transcriptional and post-transcriptional regulation.

Active Transport, Cell Nucleus↗

Improving selection of alphaIIbbeta3-binding phage antibodies with increased reactivity derived from immunized donors.

Although many studies of the immune response in polytransfused Glanzmann thrombasthenia (GT) patients and in autoimmune thrombocytopenic purpura (AITP) have demonstrated the frequent development of Abs directed against the alphaIIbbeta3 integrin, little is known about the induced anti-alphaIIbbeta3 autoantibodies at the molecular level. Phage display is a powerful technology for selecting and engineering mAbs expressed on the surface of filamentous bacteriophage. Combinatorial libraries of single-chain IgG were constructed from splenocytes from two patients with AITP and one patient with GT. In a previous study, activated platelets or alphaIIbbeta3-expressing CHO cells selection was performed to isolate human IgG anti-alphaIIbbeta3 binding fragments using combinatorial libraries created from the B cells of a GT and an AITP patient. However, we have experienced practical problems such as enrichment of truncated antibodies during selection. We decided to test prolonged treatments with elution agents after screening on the purified form of the alphaIIbbeta3 integrin activated with the RGD peptide. We obtained a higher percentage of clones with full-size antibody fragments as well as an enrichment of more specific alphaIIbbeta3-binding phage-Abs. Some of them, recognizing the activated form of the integrin, would be interesting to further study as potential diagnostic or therapeutic agents in acute coronary syndromes. Sequencing of selected phage-Abs revealed that they used different VH and VL genes with, for the majority of them, a high level of extensive hypermutations in the complementarity determining regions, indicating the diversity of the antigen-driven immune response that occurred in GT and AITP patients.

Animals↗

Severe cardiac failure associated with presumed jellyfish sting. Irukandji syndrome?

We present a retrospective review of twelve cases of Irukandji syndrome associated with pulmonary oedema. This is a life-threatening envenoming due to a presumed jellyfish sting throughout Northern Australia, although only one case occurred outside North Queensland. Patients presented with significant and ongoing pain, tachycardia and hypertension. Half the patients became hypotensive requiring inotropic support. Cardiac echocardiography revealed significant cardiac dysfunction. Six patients required ventilatory support. There was no death reported due to pulmonary oedema, but one patient died of intracerebral haemorrhage. We believe patients may develop a toxin associated cardiomyopathy, and jellyfish other than Carukia barnesi may be responsible. As there is confusion with nomenclature, Carukia barnesi should be known as the Barnes jellyfish, and the diagnosis of cardiotoxic marine envenoming is suggested for any patient who has been stung by a jellyfish, develops no or minimal skin markings, and develops cardiogenic pulmonary oedema associated with Irukandji syndrome.

Adolescent↗