Publications by authors named "Hawthorn J"

Objective: To explore the experiences of 'spoke site' allied health and child and family health clinicians in the provision of care through a pilot 'hub and spoke' model Virtual Paediatric Feeding Clinic (VPFC) outreach service.

Design: The study was qualitative, with data from virtual interview transcripts analysed using thematic analysis.

Setting: Orange Health Service ('hub site') and seven community health centres within the Western NSW Local Health District ('spoke sites').

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Background: The eyes are particularly important aesthetic features of the face and revitalization of the infraorbital region has become a focus of aesthetic treatments. Published infraorbital scales to date have limitations in that they have been descriptive, subjective, or have used computer-generated images. Thus, there is an unmet need for a validated scale based on actual images.

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The transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative disorders characterised by the accumulation of a pathological form of a host protein known as prion protein (PrP). The validation of abnormal PrP detection techniques is fundamental to allow the use of high-throughput laboratory based tests, avoiding the limitations of bioassays. We used scrapie, a prototype TSE, to examine the relationship between infectivity and laboratory based diagnostic tools.

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Quality of life (QOL) measures have assumed increasing importance in assessing the impact of therapeutic drugs and interventions on patients and in making judgements about their cost-effectiveness. Important treatment decisions and crucial funding strategies involve QOL data and, for patients with a disease such as advanced breast cancer that impinges on their life expectancy, QOL can become a hugely important consideration. Yet, despite this, there is a lack of consensus on what defines an appropriate QOL measure, and inconsistency in the instruments that are chosen to measure it.

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Recently, we reported that PrP(Sc), a surrogate marker for prion disease, is associated with the cellular fraction of blood from scrapie-infected sheep using a ligand-based immunoassay. In the study reported here, we found that a subset of peripheral blood mononuclear cells is most likely to sequester PrP(Sc) during both the preclinical phase of disease and at clinical end point. These cells had a cell surface phenotype of MHC class II DQ(+), surface immunoglobulin(+), CD11b(+), CD11c(+), CD21(+/)(-), which is consistent with a subpopulation of B cells.

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The role of blood in the iatrogenic transmission of transmissible spongiform encephalopathy (TSE) or prion disease has become an increasing concern since the reports of variant Creutzfeldt-Jakob disease (vCJD) transmission through blood transfusion from humans with subclinical infection. The development of highly sensitive rapid assays to screen for prion infection in blood is of high priority in order to facilitate the prevention of transmission via blood and blood products. In the present study we show that PrP(sc), a surrogate marker for TSE infection, can be detected in cells isolated from the blood from naturally and experimentally infected sheep by using a rapid ligand-based immunoassay.

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Milk specimens were collected from lactating cows that had previously been challenged with bovine spongiform encephalopathy (BSE)-infected brain at 4-6 months of age. One group of 10 animals received a single oral dose of 100 g, a second group received 1 g and the third was made up of unexposed controls. The cows were inseminated artificially, and calved at approximately 2 years of age and annually thereafter.

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Respiratory support using negative extrathoracic pressure or high-frequency chest wall oscillation was used to treat 3 infants with cystic fibrosis and respiratory failure who had not responded to maximal medical therapy. Beneficial clinical effects were noted in all three cases. Pulmonary function testing was performed in 2 cases, and measures of compliance increased.

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In recent years the role of the area postrema in the emetic reflex has been predominant and the involvement of the abdominal visceral innervation has tended to be overlooked. This paper attempts to redress the balance reflex by reviewing aspects of the existing literature and complementing this with original studies from the ferret. In view of the widespread use of the ferret in studies of emesis and particularly in the characterization of the antiemetic actions of 5-HT3 receptor antagonist, the opportunity is taken to assess the suitability of this species for studies of emesis.

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A new group of selective 5HT3 antagonists are proving to be effective anti-emetics for cytotoxic and radiation induced vomiting in both animal models and man. Current anti-emetic regimens often benefit from combination therapy, in particular the efficacy of metoclopramide (which can be a weak 5HT3 antagonist), can be improved by combination with dexamethasone, another anti-emetic. Hence it was of interest to evaluate whether a 5HT3 receptor antagonist GR38032F could be improved by combination with dexamethasone.

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Apomorphine, a centrally-acting emetic, was administered subcutaneously (50 micrograms/kg) to nine normal subjects (four male, five female; aged 22-36 years) and four patients with idiopathic diabetes insipidus (DI) (one male, three female; aged 24-49 years). In the normal subjects this stimulus caused nausea (and vomiting in seven of nine) with a latency of 9.5 +/- 0.

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The aim of this study was to investigate whether direct afferent stimulation of the abdominal vagus could promote release of the neurohypophyseal hormones. The nucleus of the solitary tract is the major recipient of vagal afferent information, and this region of the brainstem may also be activated by stimulation of the area postrema. For this reason apomorphine, a D2 dopaminergic agonist which acts on the area postrema, and can evoke vasopressin secretion in man, was also investigated for its effect on vasopressin and oxytocin release.

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We have used the ferret as an animal model to investigate the emetic action of the cytotoxic drugs cyclophosphamide and cis-platin. Using selective nerve lesions, a crucial role for the abdominal innervation in the genesis of retching and vomiting in response to these agents has been demonstrated. A combination of bilateral abdominal vagotomy and greater splanchnic nerve section can totally abolish retching and vomiting in response to intraperitoneal cis-platin or intravenous cyclophosphamide.

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The neurophysiology of vomiting.

Baillieres Clin Gastroenterol

January 1988

Nausea and vomiting can be induced by a wide variety of stimuli such as pregnancy, space travel, raised intracranial pressure, radiation and cytotoxic drugs. The mechanisms by which all these diverse stimuli culminate in a final common act is unknown. From studies in the 1950s a model of the emetic reflex emerged consisting of a chemoreceptor trigger zone in the area postrema and a vomiting centre in the brain stem.

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GR38032F is a highly selective 5HT3-receptor antagonist which inhibits vomiting induced by cisplatin, cyclophosphamide or X-radiation in the ferret. Since cisplatin selectively increased the levels of 5HT and 5HIAA in the intestinal mucosa, a possible site of the antiemetic action of GR38032F may be on 5HT3-receptors on vagal afferents in the small intestine. The potent antiemetic action of GR38032F should be of clinical value in reducing the nausea and vomiting associated with radiotherapy or chemotherapy of cancer.

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The distribution of oxytocin and vasopressin in the adrenals of rat, cow, hamster and guinea pig has been studied by use of immunohistochemical techniques. In all the species studied the adrenal cortex contained both peptides; the staining in the zona glomerulosa being more intense than that in zona fasciculata or zona reticularis. The medulla, however, showed considerable species variation.

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Recent studies have implicated 5-HT3(5-HT-M) receptors in the genesis of retching and vomiting evoked by antineoplastic agents. Such receptors have so far only been located peripherally, notably on the vagus. Therefore, the effects of bilateral abdominal vagotomy and antagonism of 5-HT3 receptors have been investigated on retching and vomiting induced by radiation.

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15 patients receiving cytotoxic drugs (other than cisplatin) that had previously produced nausea and vomiting refractory to first-line antiemetics were given a selective 5-HT3 receptor antagonist (GR38032F), 4 mg intravenously and 4 mg orally, immediately before chemotherapy, the oral dose being repeated 5 and 10 h later. Nausea, vomiting, and side-effects were recorded for the ensuing 24 h. The 15 patients received a total of thirty-one courses of chemotherapy.

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We have measured serum thyroxine (T4), triidothyronine (T3), thyroid-stimulating hormone (TSH) free thyroxine (FT4) and thyroxine-binding globulin (TBG) levels in a total of 5 post-menopausal women who were receiving oestrogen alone (Premarin, n = 19), progestogen alone (Primolut-N, n = 12), a combination of oestrogen and progestogen (Prempak C, n = 14) or no treatment (control group, n = 12). No differences were observed between the Premarin and Prempak C groups; both exhibited elevated T4 and TBG levels, although free thyroxin (FT4) and T4/TBG concentrations were normal relative to those in the control group. The Primolut-N subjects showed subnormal T3 and FT4 levels relative to the controls.

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The content of arginine vasopressin and oxytocin in various extrahypothalamic sites of the rat brain and spinal cord was determined by specific radioimmunoassays after lesions had been made in either the paraventricular (PVN), supraoptic (SON) or suprachiasmatic nuclei (SCN). In some animals all 3 nuclei were destroyed together. The PVN provided a considerable amount of the vasopressin innervation of the solitary tract nucleus, and most of that in the spinal cord.

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Vasopressin is known to mediate its action on the kidney through increasing the concentrations of cyclic AMP. As vasopressin is widely distributed in many extra hypothalamic areas of the brain and can be shown to act centrally, we have investigated the effect of vasopressin on cyclic AMP levels in homogenates of the striatal and locus coeruleus areas. In contrast with the effect obtained on the kidney, vasopressin did not stimulate adenyl cyclase activity in rat brain homogenates in a dose-related manner.

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While immunohistochemistry has been used extensively to map both oxytocin (OT) and vasopressin (VP) pathways in the brain, little information is available concerning the quantitative distribution of these hormones--particularly oxytocin. We have isolated oxytocin from extrahypothalamic regions of the rat brain and shown it to behave identically with standard oxytocin in radioimmunoassay (RIA) and on high-performance liquid chromatography. Using sensitive RIA we have measured and compared levels of both oxytocin and vasopressin in the rat brain.

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The subcellular localization of vasopressin (VP) from extra-hypothalamic areas of rat brain was investigated by measuring its distribution (a) along a continuous sucrose gradient; (b) during the preparation of isolated nerve endings (synaptosomes) and (c) during the preparation of synaptic vesicles. Quite large amounts of vasopressin are isolated in the same fractions as mitochondria, as well as synaptosomes. Osmotic rupture of membrane bound organelles in the homogenate results in the vasopressin being measured largely in the fraction containing synaptic vesicles.

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