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Biomedical subjects

L Austin

Publications and source records attributed to L Austin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Nurse-patient relationships: the context of nurse prescribing.

Nurse prescribing was initiated in the United Kingdom in October 1994 in eight demonstration sites. The evaluation of this extension to the community nurses' role explored both economic and qualitative benefits to patients, carers, nurses and other health care professionals. In this paper the impact of nurse prescribing on patients is explored. Benefits experienced by patients are described along with the difficulties encountered. The patients' views regarding nurses as prescribers are also explored. Data were collected by means of interviews with patients/carers, the focus of which was to evaluate changes associated with nurse prescribing. Patients raised a number of issues associated with their relationship with nurses. Patients valued nurses for both their accessibility and approachability, which led them to discuss health issues which would not otherwise have been brought to the attention of the general practitioner. The arguments which support the incorporation of these qualities into an expanded nursing role are presented.

Attitude to Health↗
PubMed1997

Nurses' and GPs' views of the nurse prescribers' formulary.

This article presents the findings from the evaluation of nurse prescribing, undertaken in eight demonstration sites since October 1994. The authors examine in particular the nurses' prescribing behaviour and the type of items nurses and GPs would like to see added to the formulary. The opportunities for prescribing and the limitations of the formulary for health visitors and practice nurses are highlighted.

Attitude of Health Personnel↗
PubMed1997

The role of leukemia inhibitory factor in skeletal muscle regeneration.

Although a number of cytokines have been implicated in tissue regeneration, it is unknown which ones actually function in vivo. Here, we use mice with a targeted mutation in the leukemia inhibitory factor (LIF) gene to examine the role of LIF in muscle regeneration. Using a muscle crush model, we show that muscle regeneration in LIF knockout mice is significantly, reduced compared to control littermates. Further, targeted infusion of LIF in both normal and LIF knockout animals stimulated muscle regeneration, but the stimulation observed was much greater in the mutant animals than in controls. In contrast, interleukin-6 and transforming growth factor-alpha, which also stimulate myoblast proliferation in vitro, had no effect on regeneration. These findings demonstrate directly that LIF is involved in regeneration of injured muscle and points to the use of LIF as a therapeutic agent in the treatment of neuromuscular disease.

Animals↗
PubMed1997

Controlled release of leukaemia inhibitory factor (LIF) to tissues.

Leukaemia inhibitory factor (LIF) has been shown to effectively enhance skeletal muscle regeneration after mechanical injury and it may have potential therapeutic use in the muscular dystrophies as well as peripheral nerve repair after injury. When LIF is applied systemically to an animal, it is rapidly removed with a biological half life of only a few minutes, and at high doses it exhibits toxic effects. Calcium alginate rods have been developed for the purpose of insertion adjacent to skeletal muscles. These rods, when charged with LIF will release the growth factor to the muscle at a rate of less than 1% per day and for a period extending to several months. In addition, tubes of alginate are described which will be suitable for the continuous supply of LIF to repaired peripheral nerve.

Alginates↗
PubMed1996

Leukaemia inhibitory factor treatment stimulates muscle regeneration in the mdx mouse.

A number of growth factors are involved in coordinating muscle cell proliferation and differentiation, particularly after injury and in disease. Leukaemia inhibitory factor (LIF) strongly stimulates the proliferation of myoblasts in vitro and in vivo and its expression in muscle after injury suggests that LIF may have a role as a trauma factor. The mdx mouse was used to study the effects of LIF on in vivo muscle regeneration during disease. The rationale for using trophic factors such as LIF to treat neuromuscular disease includes the understanding that these molecules show some degree of selectivity for the population of cells in which they are effective. LIF was administered to muscle of the mdx mouse using osmotic pumps implanted subcutaneously in unrestrained mice. The growth factor was continuously delivered into the vastus lateralis muscle at 7 U/mu 1 for 7 days via a catheter. The results show that LIF increased the rate of muscle regeneration in mdx mice by stimulating the formation of larger myotubes. LIF treatment also increased the number of regenerating myotubes in the perfused area. This myotrophic action indicates that LIF contributes to muscle regeneration. Together with its known neurotrophic action, LIF is a potential therapeutic agent for the treatment of neuromuscular disease.

Animals↗
PubMed1996

Leukemia inhibitory factor and interleukin-6 are produced by diseased and regenerating skeletal muscle.

The process of skeletal muscle regeneration following injury or disease involves locally produced growth factors which control cellular proliferation and differentiation. Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) have previously been shown to promote the proliferation of myoblasts in vitro, and thus may be involved in muscle regeneration. In the present investigation, the in vivo expression of these two myogenic growth factors was examined in regenerating muscle after a crush injury of wild type mice, and in diseased skeletal muscle and diaphragm of the mdxmouse. Using Reverse transcription polymerase chain reaction we have demonstrated that while normal muscle rarely expresses mRNA for these two molecules, there is significant up-regulation following injury, coinciding with the active period of muscle regeneration. This suggests these molecules act as locally produced trauma factors. This observation is reinforced in mdxmouse muscle, which is undergoing a cycle of degeneration and regeneration, and expresses both LIF and IL-6. Using in situ hybridization we have localized mRNA for LIF expression in the mdx diaphragm, suggesting that local production of these molecules by regenerating muscle itself, as well as by other cells in muscle, plays an important role in muscle regeneration.

Animals↗
PubMed1996

Cranial irradiation after surgical excision of brain metastases in melanoma patients.

BACKGROUND: Brain metastases account for 20-54% of reported deaths from melanoma. Duration and quality of survival depend on the extent of metastatic disease and response to treatment. Treatment goals are palliation of symptoms and prolongation of life. No studies have directly compared surgery alone and surgery with adjunctive cranial irradiation in patients with solitary brain metastases. METHODS: We evaluated postoperative adjunctive cranial irradiation in 34 patients with solitary brain metastases. RESULTS: Overall survival was significantly improved in the 22 patients who received adjunctive cranial irradiation versus that in the 12 patients who had surgery alone. Twenty-eight patients subsequently relapsed. Nine of 10 patients with surgery alone had brain recurrence as a component of failure. Six of 10 patients not receiving irradiation had brain recurrences as a component of relapse at multiple sites whereas only 1 of 18 patients receiving irradiation relapsed with the brain. CONCLUSIONS: Adjunctive cranial irradiation is justified for melanoma patients who undergo surgical therapy for solitary brain metastases. Survival in patients presenting with solitary brain metastases was improved by a reduction of relapse in the brain as a component of failure by combined surgery and irradiation.

Adult↗
PubMed1996

Up-regulation of leukaemia inhibitory factor and interleukin-6 in transected sciatic nerve and muscle following denervation.

Leukaemia inhibitory factor (LIF) and Interleukin-6 (IL-6) are multifunctional cytokines that are related on the basis of their predicted structural similarities and shared signal transducing receptor components. Both these factors stimulate myoblast proliferation, and whereas LIF is neurotrophic for sensory neurons, and for the motor neurons which innervate muscle, IL-6 has only been reported to act on a population of septal neurons in the brain. We have looked at the effect of peripheral nerve trauma on the expression of these factors. We show here that whereas LIF and IL-6 mRNAs are expressed in low levels in normal sciatic nerve and skeletal muscle, there is significant up-regulation in the nerve segments after injury, with proximally and distally. There is also an increase in LIF and IL-6 expression in the denervated muscle located largely in the muscle cells. In addition, while there is retrograde axonal transport of LIF by the sciatic nerve, IL-6 is not retrogradely transported, and as a result, IL-6 does not stimulate the survival of sensory neurons in vitro. Both growth factors are produced by Schwann cells. These results show a rapid response in the expression of these genes after injury and suggest that LIF and IL-6 act as trauma factors but with different roles in injured peripheral nerve.

Animals↗
PubMed1996

PUVA treatment selectively induces a cell cycle block and subsequent apoptosis in human T-lymphocytes.

Psoralen plus UVA (320-400 nm radiation; PUVA) is a highly effective therapy for cutaneous diseases caused by skin infiltration with normal or neoplastic T-lymphocytes. In comparing the effects of pharmacologically relevant, low-dose PUVA treatment on growth of human keratinocytes, peripheral blood leukocytes (PBMC), and T-lymphocyte cell lines, we determined that PBMC or T-lymphocytes were > 50-fold more sensitive to cytotoxic effects of PUVA, while antiproliferative effects were produced by similar PUVA levels in all cell types. Low doses of PUVA (10 ng/mL 8-methoxypsoralen and 1-2 J/cm2) were highly cytotoxic for phytohemagglutinin-activated normal lymphocytes or transformed T-lymphocytes as assessed by two viability assays and by flow cytofluorometry. Altered lymphocyte morphology, nuclear fragmentation, TUNEL+ nuclei or nuclear fragments, and the appearance of a sub-G1 DNA peak indicated that cell death occurred by apoptosis, beginning about 1 day after PUVA treatment and continuing for several days thereafter. From assessment of cell cycle progression in mimosine-synchronized cells, PUVA treatment markedly slowed cell cycle progression, eventually producing cell cycle arrest and apoptotic entry. We propose that the probable basis for disease remissions (psoriasis, cutaneous T-cell lymphoma) produced by PUVA treatment is through selective cytotoxic effects on clonal T-lymphocyte populations that are concentrated in diseased skin.

Apoptosis↗
PubMed1995

Specific binding of leukemia inhibitory factor to murine myoblasts in culture.

Leukemia inhibitory factor (LIF) is a member of the cytokine family of growth factors. It has been shown to exert a variety of actions on a diverse range of cell types, including neuronal, bone, and hemopoietic cells (Hilton, 1992, Trends Biochem. Sci., 17:72-76). In many of these cell types, studies have indicated the presence of specific receptors for LIF (Godard et al., 1982, J. Biol. Chem., 267: 3214-3222; Hilton et al., Proc. Natl. Acad. Sci. USA, 85:5971-5975; Hilton and Nicola, 1992, J. Biol. Chem., 267:10238-10247.). The mechanism by which these receptors act is believed to involve tyrosine phosphorylation and the signal transducing receptor component gp130. We have previously shown that LIF is capable of inducing both human and murine myoblasts to proliferate in culture (Austin et al., 1992, J. Neurol. Sci., 112:185-191). We now report that LIF binds specifically to receptors on the surface of myoblasts, with an equilibrium dissociation constant of 400 pM and the number of receptors per cell varies with cell density. Binding competition studies showed that LIF binding to these receptor sites was not competed for by a number of other growth factors which stimulate myoblast proliferation including basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF alpha), insulin-like growth factor 1 (IGF-1), and interleukin-6 (IL-6). There was a time and concentration-dependent down-regulation of receptor numbers following preincubation of myoblasts with LIF. The processing of these receptors subsequent to binding, involves as a first step, internalization and degradation by the myoblast. LIF appeared to stimulate myoblast proliferation rather than cell survival.

Animals↗
PubMed1995

Dynamic cardiomyoplasty.

Dynamic cardiomyoplasty is a promising new technique that appears to effect symptomatic improvement in patients with NYHA class III heart failure. Objective improvement in systolic performance of the left ventricle appears small but remains to be further defined. No survival advantage has yet been realized, although this may be seen as the technique is further refined and operative risk curtailed. Mechanism of action may include a girdling effect that prevents progressive left ventricular dilatation. This effect may be independent of any role in augmenting systolic performance. Randomized clinical trials currently in progress will provide definitive answers within the next few years to these important questions.

Adult↗
PubMed1994

Leukemia inhibitory factor (LIF) infusion stimulates skeletal muscle regeneration after injury: injured muscle expresses lif mRNA.

Leukemia inhibitory factor (LIF) is known to stimulate myoblast growth in culture via direct receptor mediated mechanisms, but it does not suppress myoblast fusion in vitro. We show here that LIF is also effective in vivo, using a muscle crush model. Administration of LIF to the site of the crush results in an increased rate of regeneration of the injured muscle. LIF stimulates an increase in the size of the muscle fibers rather than an increase in total number. Perfusion of 125I-labelled LIF (125I-LIF) at the site of the crush leads to uptake of the great majority of 125I-LIF into the muscle, which suggests that LIF is acting directly at the site of injury. Further, following crush injury LIF mRNA synthesis commences in the muscle. These data provide evidence that LIF is acting as a natural trauma factor in vivo and is actively involved in muscle regeneration.

Animals↗
PubMed1992

Effects of leukaemia inhibitory factor and other cytokines on murine and human myoblast proliferation.

It has been shown previously that leukaemia inhibitory factor (LIF) and transforming growth factor-alpha (TGF-alpha) stimulate proliferation of primary cultures of murine myoblasts. We now show that human myoblasts respond in a similar manner to LIF and TGF-alpha. These responses occur over a range of growth conditions. There are total additive effects in both human and murine myoblasts between LIF and TGF-alpha and LIF and fibroblast growth factor-beta (FGF-beta), but not between LIF and interleukin-6 (IL-6) or insulin-like growth factor 1 (IGF-1). The LIF response is initiated by a short exposure to the cytokine and is maintained for prolonged periods in its absence.

Animals↗
PubMed1992

Potential oxyradical damage and energy status in individual muscle fibres from degenerating muscle diseases.

Inherited degenerating muscle diseases result in disintegration of muscle fibres, which is initiated by a lack of or alteration to a muscle protein. In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) the protein is known to be dystrophin. The cellular function of dystrophin is not known in any detail but its absence appears to lead to a weakening of the sarcolemma. It has been proposed by Murphy and Kehrer that this leads ultimately to increased oxyradical production which may accelerate the degeneration. Studies have been carried out on individual muscle fibres derived from biopsy samples from patients with a number of degenerative muscle diseases. The glutathione cycling components, in particular glutathione and glutathione peroxidase, are significantly elevated in DMD, BMD and other diseases. Glutathione reductase is also elevated in some of these diseases. Energy producing systems are also affected particularly in intact fibres of muscle derived from muscle at an advanced stage of the disease. These results suggest that oxyradical damage may occur as a secondary consequence of muscle degenerating disease, leading to a breakdown in the glycogenolytic energy producing system.

Adenosine Diphosphate↗
PubMed1991

Duchenne muscular dystrophy and dystrophin: sequence homology observations.

Duchenne muscular dystrophy (DMD) is a genetically transmitted disease characterized by progressive muscle weakness and usually leads to death. DMD results from the absence, deficiency or dysfunction of the protein dystrophin. Analysis of protein data bases, including homology alignments and domain recognition patterns, have located highly significant correlations between dystrophin and other calcium regulating proteins. In particular, a major portion of the dystrophin sequence has been found to contain repeating units of approximately 100 amino acid residues. These repeating units were found to exhibit significant homology to troponin I. Troponin I has been found to bind to the calcium binding proteins calmodulin and troponin C. The regions of highest homology were characterized by patterns of high localization of charged amino acids and thus could represent a possible calmodulin or troponin C surface accessible binding site. Since subcellular localization studies have indicated that dystrophin is associated with the triadic junction, these findings imply that dystrophin could be involved in controlling intracellular calcium homeostasis.

Amino Acid Sequence↗
PubMed1991

Stimulation of myoblast proliferation in culture by leukaemia inhibitory factor and other cytokines.

Significant stimulation of growth of myoblasts in culture is achieved by leukemia inhibitory factor (LIF). The optimum activity of this cytokine occurs at about 6 pM LIF. Interleukin-6 (IL-6) also stimulates cultured myoblasts but to a lesser degree than LIF and the effect is not maintained for extended culture periods. In addition, transforming growth factor-alpha (TGF-alpha) also increases the growth rate of myoblasts but only after a considerable lag phase. All 3 cytokines may be of value in the large scale production of myoblasts for use in the potential treatment of primary myopathies by injection of cultured myoblasts into diseased muscle to form genetically complete muscle fibres after fusion of the myoblasts in situ. Their potential use is enhanced in that at least under the conditions used here they do not stimulate fibroblast proliferation.

Animals↗
PubMed1991

Brain MRI in obsessive-compulsive disorder.

Magnetic resonance imaging (MRI) brain scans were performed on 12 patients with obsessive-compulsive disorder and 12 healthy controls. Measurements of the area of the head of the caudate nucleus, cingulate gyrus thickness, intracaudate/frontal horn ratio, and area of the corpus callosum did not differ between the two groups. These limited data do not support the presence of a consistent gross brain structural abnormality in obsessive-compulsive disorder. Further studies using other anatomic measurements and other brain structural imaging techniques are warranted.

Adult↗