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Biomedical subjects

L Austin

Publications and source records attributed to L Austin.

At least 19 recordsLinked to original sources
PubMed2003

Short-term beta-amyloid vaccinations do not improve cognitive performance in cognitively impaired APP + PS1 mice.

Prior work demonstrated that beta-amyloid (A beta) immunotherapy for 8 months prevented cognitive impairment in 16-month-old APP + PS1 transgenic mice. In the present study, 4 immunizations administered biweekly to cognitively impaired 16-month-old transgenic mice could not reverse deficits in working memory or reference memory in the radial arm water maze or in visual platform recognition, possibly because of inadequate antibody exposure. Nontransgenic mice showed cognitive savings between the 16- and 18-month test periods, but the transgenic groups did not. These results suggest that a longer period of active immunotherapy, or passive immunization, may be required to provide sufficient antibody titers to improve cognition in older transgenic mice. A beta-based immunotherapy for Alzheimer's disease will likely be more successful prophylactically than therapeutically.

Amyloid beta-Peptides↗
PubMed2001

In vivo and in vitro correction of the mdx dystrophin gene nonsense mutation by short-fragment homologous replacement.

Targeted genetic correction of mutations in cells is a potential strategy for treating human conditions that involve nonsense, missense, and transcriptional splice junction mutations. One method of targeted gene repair, single-stranded short-fragment homologous replacement (ssSFHR), has been successful in repairing the common deltaF508 3-bp microdeletion at the cystic fibrosis transmembrane conductance regulator (CFTR) locus in 1% of airway epithelial cells in culture. This study investigates in vitro and in vivo application of a double-stranded method variant of SFHR gene repair to the mdx mouse model of Duchenne muscular dystrophy (DMD). A 603-bp wild-type PCR product was used to repair the exon 23 C-to-T mdx nonsense transition at the Xp21.1 dys locus in cultured myoblasts and in tibialis anterior (TA) from male mdx mice. Multiple transfection and variation of lipofection reagent both improved in vitro SFHR efficiency, with successful conversion of mdx to wild-type nucleotide at the dys locus achieved in 15 to 20% of cultured loci and in 0.0005 to 0.1% of TA. The genetic correction of mdx myoblasts was shown to persist for up to 28 days in culture and for at least 3 weeks in TA. While a high frequency of in vitro gene repair was observed, the lipofection used here appeared to have adverse effects on subsequent cell viability and corrected cells did not express dystrophin transcript. With further improvements to in vitro and in vivo gene repair efficiencies, SFHR may find some application in DMD and other genetic neuromuscular disorders in humans.

Animals↗
PubMed2001

Leukemia inhibitory factor enhances regeneration in skeletal muscles after myoblast transplantation.

Cell-based therapies, such as myoblast transfer therapy, are likely to become an integral part of any approach to treat myopathies such as Duchenne muscular dystrophy. Previous studies have shown that an increased level of regeneration in the host muscle enhances incorporation of donor myoblasts. Leukemia inhibitory factor (LIF) increases the number of dystrophic fibers expressing dystrophin after myoblast transplantation and enhances regeneration in injured and diseased muscle. Morphometric analysis was used to investigate whether an increased level of regeneration is induced by LIF after myoblast transplantation. We found that, in muscles treated with LIF, the number of fibers undergoing regeneration was increased. The increased incorporation of donor myoblasts and thus dystrophin expression induced by LIF may be due, at least in part, to an increased level of regeneration of dystrophic muscle.

Animals↗
PubMed2001

Presymptomatic motor neuron loss and reactive astrocytosis in the SOD1 mouse model of amyotrophic lateral sclerosis.

In familial amyotrophic lateral sclerosis (fALS), there is a need to establish more precisely the progression of the disease, particularly whether there is gradual presymptomatic neuronal loss or an abrupt loss coinciding with the symptomatic stage. To elucidate this, we investigated the progression of motor neuron loss through morphological techniques, reactive astrocytosis, and expression of ubiquitin and neurofilament proteins, by immunohistochemistry, in SOD1 G93A mice with a protracted disease course and control mice. Loss of motor neurons in SOD1 G93A mice followed a biphasic progression, with an initial loss at 126 days of age, followed by a gradual loss from onset of symptoms through to end-stage disease. Reactive astrocytosis was first observed at 70 days of age and showed a gradual increase through to end-stage disease. This suggests that there is a need for early detection of fALS cases, and potential therapeutic treatments may be more beneficial if administered at an early stage.

Amyotrophic Lateral Sclerosis↗
PubMed2001

The role of physicians in mammography referral for older Caribbean women in Canada.

BACKGROUND: Despite the fact that the proportion of immigrant and minority women who consult a general practitioner about their health is similar to that of their Canadian-born counterparts, studies suggest that they are less likely to be screened for breast cancer. This study examines physician characteristics associated with mammography referral and perceived barriers to mammography among family physicians serving the Caribbean community of Toronto. METHODS: The study consisted of a mail-back family physician survey. RESULTS: Among the 64 physicians who responded to the survey, over half reported that they were "very likely" to refer women for mammography during a regular preventive check-up. Among physician variables, only the amount of time spent on patient education was significantly associated with the likelihood of referral. Regarding perceived barriers, for male physicians, patient refusal and intervention causing patient discomfort were significantly associated with referral. For female physicians, only forgetting to provide service was identified as a significant barrier to referral. INTERPRETATION: An increased emphasis on patient education may help to increase screening referral among all physicians. Gender differences in perceived barriers to referral suggest that the gender of the physician is of major importance to the Caribbean community.

Aged↗
PubMed2000

Increased levels of leukemia inhibitory factor mRNA in muscular dystrophy and human muscle trauma.

Leukemia inhibitory factor (LIF) is an important muscle trauma factor both after crush injury and in the mdx mouse dystrophy model. It is important to establish which growth factors have a role in human muscle regeneration due to potential clinical therapeutic applications. As there is limited information concerning LIF expression in human muscle, we investigated the relative levels of LIF messenger ribonucleic acid (mRNA) in human muscle injury. Semiquantitative reverse transcriptase followed by polymerase chain reaction was used to amplify LIF message. We found that although LIF mRNA is expressed in low levels in control muscle, a sevenfold increase occurred after orthopedic muscle trauma and a marked 19-fold increase in dystrophic muscle (P < 0.002). These results indicate that LIF mRNA is upregulated in surgical and especially medical muscle injury with repeated myonecrosis. Muscle growth factors such as LIF may assist in future muscle rehabilitation after injury.

Adolescent↗
PubMed2000

Leukemia inhibitory factor ameliorates muscle fiber degeneration in the mdx mouse.

Although the muscles of the mdx mouse lack dystrophin, the protein absent in muscles of humans affected with Duchenne muscular dystrophy (DMD), the only mdx muscle to degenerate in a manner similar to those of DMD boys is the diaphragm. We have previously shown that leukemia inhibitory factor (LIF) is a trauma factor that enhances muscle repair in vivo and, when applied exogenously, increases the fiber size of mdx skeletal muscle. Furthermore, we developed a controlled release device for LIF based on a calcium alginate rod (release rate about 0.5% per day). These rods were sutured to the abdominal surface of the hemidiaphragm of mdx mice 3 months old. At age 6 months the mice were killed and the diaphragm muscles fixed and sectioned. The sections showed obvious muscle degeneration at 3 months of age in mdx mouse diaphragms and further degeneration at 6 months in saline-perfused muscle. Hemidiaphragm muscles continuously exposed to LIF over the same period contained more normal myofibers, larger regenerated fibers, and less adipose tissue and other non-contractile tissue. Morphometric analysis of the diaphragm sections was carried out. The LIF-treated animals showed a significant increase in fiber number and size compared to saline rod controls. The amount of nonmuscle (connective tissue and adipose tissue) was significantly reduced and the maximum force-producing capacity of isolated diaphragm muscle strips was higher in LIF-treated mice. The results demonstrate that LIF treatment ameliorates the dystrophic abnormalities in mdx mouse diaphragm.

Animals↗
PubMed2000

Wound care in the community setting: clinical decision making in context.

Sixty-two community nurses in northern England of grades B and D to H were interviewed by a team of four researchers. The interviews were semi-structured, and were tape-recorded, fully transcribed and content analysed. They were conducted as part of a larger study, the aim of which was to examine community nurses' perceptions of quality in nursing care. One of the main themes the work focused on was decision-making as an element of quality. Data relating to wound care were considered from the perspective of the insights they offered into clinical decision-making. Data were interpreted in the light of a literature review in which a distinction had been made between theories which represented clinical decision-making as a linear or staged process and those which represented it as intuitive. Within the former category, three sub-categories were suggested: theorists could be divided into 'pragmatists', 'systematisers' and those who advocated 'diagnostic reasoning'. The interpretation of the data suggested that the clinical decisions made by community nurses in the area of wound care appeared largely intuitive, yet were also closely related to 'diagnostic reasoning'. They were furthermore based on a range of sources of information and justified by a number of different types of rationale.

Community Health Nursing↗
PubMed2000

The importance of 'knowing the patient': community nurses' constructions of quality in providing palliative care.

This paper reports findings from a study conducted in one community health care trust where 62 members of the district nursing team (grades B-H) were interviewed. An adaptation of the critical incident technique was used to determine factors which contributed or detracted from high quality care for a number of key areas including palliative care. The centrality of knowing the patient and his/her family emerged as an essential antecedent to the provision of high quality palliative care. Factors enabling the formation of positive relationships were given prominence in descriptions of ideal care. Strategies used to achieve this included establishing early contact with the patient and family, ensuring continuity of care, spending time with the patient and providing more than the physical aspects of care. The characteristics described by the community nurses are similar to those advocated in 'new nursing' which identifies the uniqueness of patient needs, and where the nurse-patient relationship is objectified as the vehicle through which therapeutic nursing can be delivered. The link with 'new nursing' emerges at an interesting time for community nurses. The past decade has seen many changes in the way that community nursing services are configured. The work of the district nursing service has been redefined, making the ideals of new nursing, for example holism, less achievable than they were a decade ago. This study reiterates the view that palliative care is one aspect of district nursing work that is universally valued as it lends itself to being an exemplar of excellence in terms of the potential for realizing the ideals of nursing practice. This is of increasing importance in the context of changes that militate against this ideal.

Community Health Nursing↗
PubMed2000

An evaluation of information cards as a means of improving communication between hospital and primary care for women with breast cancer.

This paper describes an intervention study aimed at improving communication between hospital services and the primary health care team. A series of information cards were developed by breast specialist secondary care professionals for members of the primary health care team. Women with breast cancer were involved in the communication pathway and were asked to take the information cards to their own general practitioner (GP) practice. It was envisaged that women would be more likely to utilize the primary health care team for information if they were aware that the primary health care team was in receipt of information specific to the treatment they had received. Women newly diagnosed with breast cancer were allocated to either an intervention (n=38) or non-intervention (n=38) group. Patient interviews were carried out around the time of diagnosis and at 4 months from diagnosis. Interviews were also carried out with 31 GPs to ascertain their views on the provision of information for women with breast cancer, and on the information cards if relevant. The study findings were interesting although not significant in terms of the direction anticipated. The cards did not impact on the utilization of the primary health care team and women in the intervention group were no more likely to utilize primary care sources of information than women in the non-intervention group. Factors such as the long-standing relationship women had with their GP, the perceived lack of specialist knowledge on the part of GPs and district nurses, and the women's perception that information seeking was not a tangible reason for primary care contact had an impact on information-seeking behaviour.

Adult↗
PubMed2000

Community nurses' perceptions of patient 'compliance' in wound care: a discourse analysis.

As part of an interview study of community nurses' perceptions of their work, 62 staff working within the district nursing service in one English National Health Service Trust (grades B-H) were asked to recount occasions when they had been involved in wound care and to discuss the ways in which working with patients who required such care could be either enhanced or made difficult. A large number of respondents expressed the view that non-compliance could pose serious problems for the management of wounds. Data relating to compliance are presented here and are interpreted in the light of discourse analysis, an approach which permits the researcher to focus on the meanings underlying the communications of research participants and to interpret those meanings in the light of social and cultural mores and influences. The authors found that non-compliance could be explained by nurses in a number of different ways. These ranged from passive resistance, which could be due to ignorance or lack of motivation, through overt refusal, to deliberate interference in order to prolong treatment. It also seeks to outline some of the factors that appear to motivate the nurses' desire to achieve compliance.

Attitude of Health Personnel↗
PubMed2000

Palliative care: community nurses' perceptions of quality.

OBJECTIVES: To identify community nurses' perceptions of quality care provision for patients requiring palliative care. DESIGN: Semi-structured interviews were conducted with community nurses working within the district nursing service. An adaptation of Flanagan's critical incident technique was employed to elicit factors associated with high or poor quality palliative care. Interviews were tape recorded and transcribed. Data were analysed using thematic content analysis, recurrent themes being agreed by the research team. SETTING: One community healthcare trust. SUBJECTS: 62 members of the district nursing team (grades B-H). RESULTS: Respondents recounted the context in which high quality palliative care could be provided, the actions required, and the indicators that suggested the desired level of care had been achieved. Key factors identified were: the early referral of patients to the district nursing service, family circumstances, the availability of time, the accessibility of services and equipment, and the relationship with other healthcare professionals and informal carers. There was a general view that a positive outcome had been achieved when patients retained control over their circumstances and died a peaceful death, in the place of their choice, supported by their family. CONCLUSIONS: Community nurses were able to articulate clearly the essential components of high quality care. Whilst these factors do not represent a comprehensive list, they are put forward as a useful starting point for standard setting and subsequent audit.

Attitude of Health Personnel↗
PubMed1999

Anterograde transport of leukemia inhibitory factor within transected sciatic nerves.

Disappointing functional recovery following peripheral nerve repair can be improved by neurotrophic growth factors. Leukemia inhibitory factor (LIF) is unique in that it has independent neurotrophic and myotrophic actions. The aim of this study was to explain this finding by establishing the existence of anterograde axonal transport of LIF from the site of nerve division to denervated muscles. Using 125I LIF, administered topically via an entubulation repair of divided rat sciatic nerve, we monitored its subsequent distribution by measuring the radioactivity associated with nerve segments and denervated muscles. We established that LIF preferentially accumulated in denervated muscles, a process we could reduce by 70% after tightly ligating the intervening nerve, confirming the presence of anterograde axonal transport. This was most likely an active mode of transport that ceased approximately 24 h after nerve division, establishing a narrow clinical time frame within which the myotrophic action of LIF could be optimized following nerve repair.

Animals↗
PubMed1999

Muscle protection following motor nerve repair in combination with leukemia inhibitory factor.

Leukemia inhibitory factor (LIF) has been shown to stimulate growth of muscle and nerve cells. In this rat study, in which the nerve to the medial head of the gastrocnemius was divided and repaired and slow-release LIF was administered at the repair site, we evaluated recovery by measuring the force of muscle contraction and of muscle bulk. Thirty-five male Sprague-Dawley rats (325-375 g) were randomly divided into 5 different groups according to type of treatment: denervated, end-to-end nerve repair, end-to-end nerve repair with LIF, neurotization, and neurotization with LIF. The contralateral side served as a nonoperated control group. Leukemia inhibitory factor was administered for 28 days to the site of the nerve repair via an implanted osmotic infusion pump. Muscle mass and muscular function were evaluated at 6 weeks using electrophysiologic techniques. The medial gastrocnemius muscle mass of the repair + LIF group was greater than the repair-alone group. The peak twitch, relative twitch, relative tetanic, and tetanic forces generated from the repair + LIF group were also significantly higher than those in the repair-alone group. Although neurotization was almost as effective as end-to-end nerve repair for reinnervating muscle, LIF had no increased effect on neurotization. These data suggest that LIF protects muscular function and reduces denervation atrophy following end-to-end nerve repair.

Animals↗
PubMed1998

Leukaemia inhibitory factor (LIF) production in a mouse model of spinal trauma.

A model of spinal trauma was developed where spinal neurones of adult mice were exposed to the excitotoxic glutamate analogue beta-N-oxylamino-L-alanine (L-BOAA). After 24 h, the injured neurones received a single dose of [125I]-LIF at the same site of the spinal cord, and 2 h later, tissues were removed to assess the distribution of leukaemia inhibitory factor (LIF). There was a significant increase in LIF binding to the injured region of the spinal cord over saline controls, and this corresponded with a significant increase in LIF mRNA expression in the same region of the cord. There was a change in the expression of ciliary neurotrophic factor, but the expression of cardiotrophin-1 (CT-1) and the common receptor subunit LIF receptor beta (LIFRbeta) did not change after neurotoxin treatment. The results add to the evidence that LIF plays a significant role in the response of adult neuronal tissue to injury.

Amino Acids, Diamino↗
PubMed1998

LIF (AM424), a promising growth factor for the treatment of ALS.

Growth factors are theoretically promising agents for ALS therapy, but have been disappointing in subcutaneous delivery due to either toxicity or lack of major efficacy. Leukaemia inhibitory factor (LIF), was named after its effect on haemopoietic cells, and belongs to a group of cytokines which includes CNTF, IL-6, CT-1, OM and IL-11. All group members use the gp130 signal transducing subunit for intracellular signalling, but show differences in biological effect. In vitro and in vivo studies on axotomy and nerve crush models demonstrate a powerful effect of LIF in the survival of both motor and sensory neurones, while reducing denervation induced muscle atrophy. Its effects in muscle also include stimulating myoblast proliferation in vitro, and up-regulation after muscle injury. LIF will also stimulate muscle regeneration in vivo when applied exogenously after injury. In published studies of both axotomy induced neuronal death and in the Wobbler mouse models LIF is active at doses of 10 microg/kg delivered systemically, well below the expected maximum tolerated dose suggested by primate safety studies. LIF is expressed in low levels by spinal cord neurones with significant up-regulation when the neurones are damaged by BOAA toxin, an excitatory amino acid associated with a form of ALS. This augments other evidence suggesting LIF is a trauma factor playing a role in the injury response of adult neuronal tissue, and may be more effective than related growth factors. Taken together, the data suggests LIF is a physiologically relevant trophic factor with implications in clinical medicine as a therapy for ALS, and a human recombinant form (AM424), entered human clinical trials during 1998.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Decision making: the context of nurse prescribing.

From October 1994 qualified district nurses and health visitors from eight demonstration sites in England have been able to prescribe from a limited list of formulary items. Data collected from nurses formed only one part of the evaluation of nurse prescribing. These data highlighted a number of areas where prescribing nurses were faced with difficult decisions. A number of authors have considered how both doctors and nurses make decisions, and the factors which may influence the decision making process. With reference to the literature this paper focuses on the findings related to decision making in the context of nurse prescribing.

Community Health Nursing↗