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Biomedical subjects

J R McPhee

Publications and source records attributed to J R McPhee.

11 recordsLinked to original sources

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 intention to hasten death: a survey of attitudes and practices of surgeons in Australia.

OBJECTIVE: To determine attitudes among surgeons in Australia to assisted death, and the proportion of surgeons who have intentionally hastened death with or without an explicit request. DESIGN: Anonymous, cross-sectional, mail-out survey between August and November 1999 PARTICIPANTS: 683 out of 992 eligible general surgeons (68.9% response rate). MAIN OUTCOME MEASURES: Proportion of respondents answering affirmatively to questions about administering excessive doses of medication with an intention to hasten death. RESULTS: 247 respondents (36.2%; 95% CI, 32.6%-39.9%) reported that, for the purpose of relieving a patient's suffering, they have given drugs in doses that they perceived to be greater than those required to relieve symptoms with the intention of hastening death. More than half of these (139 respondents; 20.4% of all respondents; 95% CI, 17.4%-23.6%) reported that they had never received an unambiguous request for a lethal dose of medication. Of all respondents, only 36 (5.3%; 95% CI, 2.9%-6.1%) reported that they had given a bolus lethal injection, or had provided the means to commit suicide, in response to an unambiguous request. CONCLUSIONS: More than a third of surgeons surveyed reported giving drugs with an intention to hasten death, often in the absence of an explicit request. However, in many instances, this may involve the use of an infusion of analgesics or sedatives, and such actions may be difficult to distinguish from accepted palliative care, except on the basis of the doctor's self-reported intention. Legal and moral distinctions based solely on a doctor's intention are problematic.

Adult↗

Transcranial magnetic stimulation in acute facial nerve injury.

OBJECTIVE/HYPOTHESIS: Available electrodiagnostic tests that are used to evaluate facial nerve injury examine the nerve distal to the stylomastoid foramen; because most facial nerve injuries are within the temporal bone, the tests cannot evaluate the nerve at or across the injury site. The interpretation of these tests depends on the predictability (or unpredictability) of distal degenerative process. Transcranial magnetic stimulation may be able to stimulate the nerve proximal to the injury site. The hypothesis of the present study is that in cases of mild traumatic facial nerve injury where axonal integrity is maintained, proximal stimulation of the nerve using higher than normal stimulus intensities to "overcome" the block at the injury site result in recordable facial nerve activity. STUDY DESIGN: A prospective controlled animal study comparing response to transcranial magnetic stimulation of the facial nerve in the following groups: mild injury, severe injury/transection, and control. METHODS: We studied 44 facial nerves in 22 cats. Fifteen nerves were subjected to mild trauma. Five nerves were severely crushed, 2 nerves were completely transected, and 22 nerves were not traumatized. All nerves were examined with the transcranial magnetic stimulation system before the trauma, immediately after the trauma, and at 3, 8, and 12 weeks after trauma. RESULTS: All nerves in the mild and severe trauma groups showed complete clinical paralysis immediately after trauma. The nerves in the mild trauma group showed significant increase in threshold as well as significant increase in latency for recordable facial muscle response to transcranial magnetic stimulation. Thresholds and latencies decreased gradually within 3 to 12 weeks and returned almost to preinjury levels. This paralleled the return of clinical facial muscle movement. In the severe trauma/transection group, the nerves had no facial muscle response to transcranial magnetic stimulation after trauma. Neither facial muscle response to transcranial magnetic stimulation nor facial muscle movements recovered. CONCLUSIONS: In cats transcranial magnetic stimulation can assess the integrity of the facial nerve after trauma and predict its potential for regeneration. This technique can excite the nerve proximal to the injury site and may play a role in the clinical evaluation of the acute traumatic facial nerve paralysis. It can be used immediately after trauma, because it does not depend on wallerian degeneration to occur.

Acute Disease↗

Impact of written information on knowledge and preferences for cardiopulmonary resuscitation.

AIM: To investigate knowledge about and attitudes to cardiopulmonary resuscitation (CPR), and to determine whether written information about CPR alters knowledge and choices made. DESIGN: Questionnaire-based survey before and immediately after provision of written information describing CPR and its risks and benefits. SUBJECTS AND SETTING: All health professionals (803) and competent inpatients (260) in a tertiary care hospital (John Hunter Hospital, Newcastle, New South Wales, Australia) in June 1994. MAIN OUTCOME MEASURES: CPR knowledge scores and choice scores (number of hypothetical clinical scenarios in which CPR would be chosen) before and after provision of information about CPR. RESULTS: Response rates were 64% (health professionals) and 58% (patients). Patients had limited awareness of procedures involved in CPR, while both patients and health professionals overestimated its success rates. Mean knowledge scores increased after provision of information: for patients, from 6.4 out of 18 (95% confidence interval [CI], 6.0-6.9) to 10.4 (95% CI, 9.9-11.1); and for health professionals, from 11.9 (95% CI, 11.7-12.1) to 13.9 (95% CI, 13.7-14.2). In contrast, mean choice scores decreased after provision of information: for patients, from 5.3 out of 12 (95% CI, 4.7-5.7) to 4.4 (95% CI, 3.9-4.8); and for health professionals, from 4.1 (95% CI, 3.9-4.2) to 3.5 (95% CI, 3.3-3.7). CONCLUSION: Our results imply that people understand and use prognostic information to make decisions about CPR. To make autonomous judgements, patients and health professionals need better education on CPR outcomes.

Adult↗

Evidence of abnormal stromelysin mRNA expression in suspected carriers of otosclerosis. A possible molecular marker.

OBJECTIVE: There is strong evidence that otosclerosis is a genetic disease affecting bone remodeling. We propose that, if otosclerosis is genetic, it will manifest itself universally, particularly at the mRNA transcription level. DESIGN: Skin biopsy specimens were taken in a single blind from human subjects who had been clinically and surgically identified as having otosclerosis. SETTING: Subjects were volunteers from the community, identified through hospital records. All procedures were carried out in a clinical research facility. PATIENTS: Twenty-one volunteers underwent a biopsy, including those positively identified as having otosclerosis (n = 4), their blood relatives (n = 8), or nonrelatives with normal hearing and no known history of otosclerosis (n = 9). INTERVENTION: Three connective tissue remodeling factors, procollagenase, prostromelysin, and tissue inhibitor of metalloprotease, were analyzed. The mRNA was extracted from each biopsy specimen, hybridized against radiolabeled cDNA, and quantitatively measured by radioautography. MAIN OUTCOME MEASURE: We expected to see significant differences in the pattern of mRNA expression for one or more of the three measured bone remodeling factors in otosclerotics, compared with age- and sex-matched negative controls. RESULTS: Two of the otosclerotic subjects had abnormally low levels of mRNA for prostromelysin and two had higher than normal levels. In three (75%) of the four, variability of mRNA expression among procollagenase, prostromelysin, and metalloprotease tissue inhibitor was higher than normal. Three (38%) of the eight relatives showed a similar pattern and two (22%) of the nine control subjects also tested as abnormal. CONCLUSION: This observed variability in otosclerotic subjects might be a manifestation of a genetic control defect, and abnormal stromelysin mRNA expression could serve as a genetic marker for otosclerosis.

Adolescent↗

Aberration of the tissue collagenase system in association with otosclerosis.

Studies of aural and other body tissues suggest that otosclerosis represents the local manifestation of a general disorder of connective tissue. In particular, collagen abnormalities have been described. We have undertaken a pilot study of the in vivo messenger RNA (mRNA) transcription for procollagenase (precursor of collagenase), as well as for stromelysin and tissue inhibitor of metalloprotease (TIMP), an activator and a specific inhibitor of tissue collagenase activity, respectively. Human skin from individuals with surgically confirmed otosclerosis was compared to skin from their family members (clinically positive and clinically negative) and from unrelated normal controls. Preliminary data indicate that on average there are significantly lower levels of mRNA production for stromelysin among individuals with otosclerosis as compared to all others tested. Similar trends were demonstrated for TIMP and procollagenase, although these did not achieve statistical significance. In addition to suggesting a pathogenetic mechanism for the development of the disease, these data could serve as the basis of possible confirmatory tests for early diagnosis of otosclerosis and as a method for evaluating the genotype of offspring of affected individuals prior to their age of clinical manifestation. This could translate into the application of prophylactic treatment regimens in the future. The proposed abnormalities also suggest candidate genes for otosclerosis.

Audiometry↗

Determinants of otic capsule formation.

The otocyst is the epithelial anlage of the membranous labyrinth that interacts with surrounding head mesenchyme tissue during formation of the otic capsule. In vitro studies were performed to gain a better understanding of the role that epithelial-mesenchymal tissue interactions play in development of the otic capsule. Parallel series of otocyst/mesenchyme (O/M) and isolated periotic mesenchyme (M) explants provided morphological and biochemical data. The results indicate that epithelial-mesenchymal tissue interactions control development of both the otic capsule and the perilymphatic spaces. The otocyst induces cartilage differentiation in periotic mesenchyme between embryonic days 11 to 13 and organizes otic capsule morphology between embryonic days 13 to 14 in the mouse embryo. The otocyst exerts a localized repression of chondrogenesis in nearby mesenchyme during perilymphatic space formation on embryonic days 12 to 14.

Animals↗

Epithelial-mesenchymal tissue interactions guiding otic capsule formation: the role of the otocyst.

The otocyst is the epithelial anlage of the membranous labyrinth which interacts with surrounding cephalic mesenchyme to form an otic capsule. A series of in vitro studies was performed to gain a better understanding of the epithelial-mesenchymal interactions involved in this process. Parallel series of otocyst/mesenchyme (O/M) and isolated periotic mesenchyme (M) explants provided morphological and biochemical data to define the role of the otocyst in organizing and directing formation of its cartilaginous otic capsule. Explants were made from mouse embryos ranging in age from 10 to 14 days of gestation, and organ cultured under identical conditions until the chronological equivalent of 16 days of gestation. Expression of chondrogenesis was determined by both histology and biochemistry. The in vitro behaviour of periotic mesenchyme explanted either with or without an otocyst supports several hypotheses that explain aspects of otic capsule development. The results indicate that prior to embryonic day 12 the otocyst alone is not sufficient to stimulate chondrogenesis of the otic capsule within O/M explants; the otocyst acts as an inductor of capsule chondrogenesis within O/M explants between embryonic days 12 to 13; isolated mesenchyme within M explants taken from 13-day-old embryos are capable of initiating in vitro chondrogenesis, but without expressing capsule morphology in the absence of the otocyst; and the isolated mesenchyme of M explants obtained from 14-day-old embryos expresses both chondrogenesis and otic capsule morphology in the absence of the otocyst. These findings suggest that the otocyst acts as an inductor of chondrogenesis of periotic mesenchyme tissue between embryonic days 11 to 13, and controls capsular morphogenesis between embryonic days 13 to 14 in the mouse embryo.

Animals↗

A comparison of morphological stages and sulfated glycosaminoglycan production during otic capsule formation: in vivo and in vitro.

The sequence of events leading to otic capsule formation in the normal mouse embryo is described for both in vivo and in vitro development. Specimens were taken from embryos at 9-16 days of gestation. The in vivo results permitted the categorization of the developmental events of capsule formation into five distinct stages: prechondrogenic, aggregation, metachromatic, early chondrogenesis, and late chondrogenesis. Synthesis of sulfated glycosaminoglycans (S-GAG) by early otic tissue complexes in vivo showed a sharp increase in the rate of S-GAG production at 14.5 days of gestation (late chondrogenesis stage). The synthesis of S-GAG in explants excised from embryos 12 days old (metachromatic stage) or older followed this same pattern of a sudden increase in S-GAG synthesis at the in vitro equivalent of 14.5 days of gestation. These otic explants underwent all five stages of capsule formation up to the morphological equivalent of 16 days gestation. Therefore, otic explants can serve as a valid model in the study of those factors (i.e., tissue interactions and extracellular matrix) which influence and direct otic capsule formation.

Animals↗

Hyaluronate production by the inner ear during otic capsule and perilymphatic space formation.

Otosclerosis has been hypothesized to result from a disorder of the extracellular matrix of the cartilaginous rests present in the adult temporal bone. Matrix relationship to bone formation and remodeling, as well as the fact that the pathogenesis of otosclerosis is expressed by the action of both of these processes, strongly suggests that more knowledge is needed about the process of otic capsule development. In pursuit of this goal, otic complexes were explanted from mouse embryos that ranged in age from 10.5 to 16 days old and were then exposed to 3H-glucosamine (50 microCi/ml) for 6 hours in vitro. Total labeled glycosaminoglycans (GAGs) and labeled hyaluronate content of each age group of otic explants were measured, and the results were compared to a developmental series of the otic regions of whole embryos stained with either toluidine blue or alcian blue. Increases in the synthesis of the total GAGs were observed on embryonic day 11 and for a prolonged period extending from gestation day 13.5 through day 16. The first increase of GAGs occurred at the initiation of metachromasia and positive staining by toluidine blue of the region of aggregated periotic mesenchyme cells that form the otic capsule. The second increase in GAGs was correlated with chondrification of the capsule. Hyaluronate production revealed a different pattern. Synthesis of hyaluronate exhibits peaks at 10.5, 12.5, and for an extended period of from 13.5 to 14.5 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗