Acute renal failure and cystic fibrosis.
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Biomedical subjects
Publications and source records attributed to J Drew.
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OBJECTIVE: To examine the anti-inflammatory activities of tea tree oil (TTO) in vivo. METHODS: Mice were sensitized to a chemical hapten, trinitrochlorobenzene, on their ventral skin and 7 days later challenged (or re-exposed) on their dorsal skin with the same hapten. RESULTS: TTO applied 30 min before or up to 7 h after to the same dorsal site as hapten challenge caused a significant reduction in skin swelling after 24 h. TTO reduced oedema but not the influx of inflammatory cells. This finding was supported by the inability of TTO to suppress TNFalpha-induced E-selectin expression by human umbilical vein endothelial cells. TTO did not suppress irritant- or ultraviolet B-induced oedema. CONCLUSION: Topical TTO, specifically the TTO components, terpinen-4-ol and alpha-terpineol can regulate the oedema associated with the efferent phase of a contact hypersensitivity response.
BACKGROUND: Neonatal necrotising enterocolitis is a serious, commonly fatal disease in premature neonates. Although feeding with expressed breast milk and other good nursery practices are partly protective, preventive measures are needed. Treating neonates enterally with a mixture of human IgA and IgG, prepared from donated blood, has been claimed to protect against necrotising enterocolitis. However, no IgA preparation is available in Australia. Our aim, therefore, was to identify whether or not enteral IgG could prevent the disorder. METHODS: We did a multicentre, double-blind, placebo- controlled trial. We randomly assigned 768 infants to receive human IgG 1200 mg/kg daily, and 761 to receive placebo, for up to 28 days. Treatment began at the same time as enteral feeding. The primary outcome measure was the proportion of infants who developed definite necrotising enterocolitis during the trial, and any deaths that resulted from the disorder in the treatment and placebo groups. Analysis was on an intention-to-treat basis. FINDINGS: 43 infants developed definite necrotising enterocolitis in the IgG group, ten of whom died. In the placebo group, 41 infants contracted the disorder and six died (p=0.47). 25 infants on IgG and 36 on placebo had suspect necrotising enterocolitis (p=0.14). INTERPRETATION: Supplementation of enteral feeds with human IgG does not reduce necrotising enterocolitis.
This Position Paper reviews the role, standards of practice, education, training and staffing requirements for radiation oncology physics. The role and standard of practice for an expert in radiation oncology physics, as defined by the ACPSEM, are consistent with the IAEA recommendations. International standards of safe practice recommend that this physics expert be authorised by a Regulatory Authority (in consultation with the professional organization). In order to accommodate the international and AHTAC recommendations or any requirements that may be set by a Regulatory Authority, the ACPSEM has defined the criteria for a physicist-in-training, a base level physicist, an advanced level physicist and an expert radiation oncology physicist. The ACPSEM shall compile separate registers for these different radiation oncology physicist categories. What constitutes a satisfactory means of establishing the number of physicists and support physics staff that is required in radiation oncology continues to be debated. The new ACPSEM workforce formula (Formula 2000) yields similar numbers to other international professional body recommendations. The ACPSEM recommends that Australian and New Zealand radiation oncology centres should aim to employ 223 and 46 radiation oncology physics staff respectively. At least 75% of this workforce should be physicists (168 in Australia and 35 in New Zealand). An additional 41 registrar physicist positions (34 in Australia and 7 in New Zealand) should be specifically created for training purposes. These registrar positions cater for the present physicist shortfall, the future expansion of radiation oncology and the expected attrition of radiation oncology physicists in the workforce. Registrar physicists shall undertake suitable tertiary education in medical physics with an organised in-house training program. The rapid advances in the theory and methodology of the new technologies for radiation oncology also require a stringent approach to maintaining a satisfactory standard of practice in radiation oncology physics. Appropriate on-going education of radiation oncology physicists as well as the educating of registrar physicists is essential. Institutional management and the ACPSEM must both play a key role in providing a means for satisfactory staff tuition on the safe and expert use of existing and new radiotherapy equipment.
The objective of this preliminary study was to evaluate more fully the role of daily spiritual experiences and daily religious/spiritual coping in the experience of individuals with pain due to rheumatoid arthritis (RA). Thirty-five individuals with RA were asked to keep a structured daily diary for 30 consecutive days. The diary included standardized measures designed to assess spiritual experiences, religious and spiritual pain coping, salience of religion in coping, religious/spiritual coping efficacy, pain, mood, and perceived social support. The participants in this study reported having spiritual experiences, such as feeling touched by the beauty of creation or feeling a desire to be closer or in union with God, on a relatively frequent basis. These participants also reported using positive religious and spiritual coping strategies much more frequently than negative religious and spiritual coping strategies. Although most of the variance in these measures was due to differences between persons, each measure also displayed a significant variability in scores from day to day. Indeed, there was just as much (or more) variability in these measures over time as there was variability in pain. Individuals who reported frequent daily spiritual experiences had higher levels of positive mood, lower levels of daily negative mood, and higher levels of each of the social support domains. Individuals who reported that religion was very salient in their coping with pain reported much higher levels of instrumental, emotional, arthritis-related, and general social support. Coping efficacy was significantly related to pain, mood, and social support in that on days that participants rated their ability to control pain and decrease pain using spiritual/religious coping methods as high, they were much less likely to have joint pain and negative mood and much more likely to have positive mood and higher levels of general social support. Taken together, these results suggest that daily spiritual experiences and daily religious/spiritual coping variables are important in understanding the experience of persons who have RA. They also suggest that newly developed daily diary methods may provide a useful methodology for studying religious and spiritual dimensions of living with arthritis.
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Apolipoprotein-E (apoE) protects against coronary artery disease via hepatic removal of atherogenic remnant lipoproteins, sequestration of cholesterol from vessel walls and local anti-oxidant, anti-platelet and anti-inflammatory actions. ApoE gene transfer may thus ameliorate a hyperlipidaemic profile and have beneficial effects at lesion sites to prevent or regress atherosclerosis, a concept endorsed by adenoviral-mediated hepatic expression studies. Here, using plasmid vectors expressing allelic human apoE2 or apoE3 isoforms, skeletal muscle was evaluated as an effective secretory platform for apoE gene augmentation. Transfected myoblasts and myotubes were found to efficiently secrete recombinant apoE in vitro as spherical 10-16 nm lipoprotein particles with pre-beta mobility. Intramuscular plasmid injection in apoE(-/-) mice, which develop spontaneous atherosclerotic plaque and xanthoma resulted in expression and secretion of apoE. Human apoE mRNA was detected by RT-PCR in injected muscles and, although concentrations of apoE3, which is rapidly cleared from plasma, were near ELISA detection limits, levels of plasma apoE2 were measurable (17.5 +/- 4.3 ng/ml). To assess whether muscle-based expression of apoE2 could inhibit atherogenesis, long-term follow-up studies were conducted. Although hyperlipidaemia was not reduced in treated animals, end-point pathology showed clear retardation of atherosclerotic and xanthomatous lesions. Up to 9 months following a single apoE2 plasmid administration, atherosclerotic lesion coverage in proximal aorta was significantly reduced by 20-30% (P < 0.01), whereas development of gross dorsal xanthoma (>5 mm diameter) was effectively reduced to zero. We conclude that expression of apoE from ectopic muscle sites has therapeutic potential to limit progression of atherosclerosis.
Inflammation is a basic pathological mechanism that underlies many diseases. An important component of the inflammatory response is the passage of plasma components and leukocytes from the blood vessel into the tissues. The endothelial monolayer lining blood vessels reacts to stimuli such as thrombin or vascular endothelial growth factor by changes in cell-cell junctions, an increase in permeability, and the leakage of plasma components into tissues. Other stimuli, such as tumor necrosis factor-alpha (TNF-alpha), are responsible for stimulating the transmigration of leukocytes. Here we show that angiopoietin-1, a cytokine essential in fetal angiogenesis, not only supports the localization of proteins such as platelet endothelial cell adhesion molecule-1 (PECAM-1) into junctions between endothelial cells and decreases the phosphorylation of PECAM-1 and vascular endothelial cadherin, but it also strengthens these junctions, as evidenced by a decrease in basal permeability and inhibition of permeability responses to thrombin and vascular endothelial growth factor. Furthermore, angiopoietin-1 inhibits TNF-alpha-stimulated leukocyte transmigration. Angiopoietin-1 may thus have a major role in maintaining the integrity of endothelial monolayers.
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We compare methods of detection of intercellular transport of the herpes simplex virus protein VP22 and of a green fluorescent protein (GFP)-VP22 fusion protein. Spread of both proteins was observed by immunofluorescence (IF) using organic fixatives. Spread of both proteins was also detected by IF after paraformaldehyde (PFA) fixation and detergent permeabilization, albeit at reduced levels. However, while spread of GFP-VP22 was observed by examining intrinsic GFP fluorescence after methanol fixation, little spread was observed after PFA fixation, suggesting that the levels of the fusion protein in recipient cells were below the detection limits of intrinsic-fluorescence or that PFA fixation quenches the fluorescence of GFP-VP22. We further considered whether elution of VP22 from methanol-fixed cells and postfixation binding to surrounding cells contributed to the increased detection of spread observed after methanol fixation. The results show that while this could occur, it appeared to be a minor effect not accounting for the observed VP22 cell-to-cell spread in culture.
To better define the role of melatonin in fish, we have compared in detail the distribution of 2-[125I]iodomelatonin binding sites with gene expression for melatonin receptor subtypes in a widely studied seasonal species, the rainbow trout. Three distinct partial sequences of the melatonin receptor gene were cloned from trout genomic DNA. Two of the sequences corresponded to the Mella receptor subtype, and one corresponded to the Mellb receptor subtype. Analysis of numerous clones failed to find a sequence equivalent to the Mel1c receptor subtype. Comparison of receptor gene expression with 2-[125I]iodomelatonin binding distribution indicated dendritic transport of the receptor. Melatonin receptors were associated predominantly with visually related areas of the trout brain, such as the thalamic region, the pretectal area, and the optic tectum. The pituitary was devoid of 2-[125I]iodomelatonin binding, and melatonin receptor gene expression was not detectable. It would appear from the results of the present study that melatonin in this species is involved primarily in the processing of visual signals. How melatonin interacts with circannual rhythms of growth and reproduction is unclear, although a direct interaction between melatonin and the hypothalamo-pituitary axis is not clearly indicated.
Inguinal hernia (IH) is relatively common in premature newborn infants, and the timing of surgical correction is controversial. We studied 40 premature infants who developed an IH and who were initially treated in a neonatal intensive care unit. Birth weight (BW) ranged from 492 to 2,401 g; 21 infants had a BW less than 1,000 g. The weight of the infants at operation ranged from 1,000 to 4,400 g. Twenty-one patients underwent herniotomy within 2 weeks after the diagnosis (short waiting group), in which 1 case of incarceration occurred; 19 waited longer than 2 weeks between diagnosis and surgery (long waiting group). Two cases of strangulation occurred in this latter group, and in 1 of those testicular necrosis occurred. Operation time was analysed in boys with bilateral herniotomy (n = 25): the short waiting group (n = 12) showed a significantly reduced operation time compared to the long waiting group (n = 13). Patients weighing less than 1,000 g at birth (n = 21) had a longer average waiting period for surgery. In the group of male patients with bilateral herniotomy, average operation time was longer in the group weighing less than 1,000 g at birth (n = 13) than in the group over 1,000 g (n = 12). Body weight at surgery did not affect operation time. It is concluded that early hernia repair should be considered in premature infants to avoid operative difficulties and gonadal ischaemia caused by incarceration.
Gene transfer by direct intramuscular injection of naked plasmid DNA has been shown to be a safe, simple but relatively inefficient method for gene delivery in vivo. Eukaryotic plasmid expression vectors incorporating the Epstein-Barr virus (EBV) origin of replication (oriP) and EBNA1 gene have been shown to act as autonomous episomally replicating gene transfer vectors which additionally provide nuclear matrix retention functions. Prolonged expression of a LacZ reporter gene and recombinant human dystrophin was shown using EBV-based plasmid vectors transfected into C2C12 mouse myoblast and myotube cultures. Intramuscular injection of EBV-based dystrophin expression plasmids into nude/mdx mice resulted in significant enhancement in the number of muscle fibres expressing recombinant dystrophin compared with a conventional vector. This effect was observed for over 10 weeks after a single administration. These results indicate the potential advantage of EBV-based expression vectors for focal plasmid-mediated gene augmentation therapy in Duchenne muscular dystrophy (DMD) and a range of other gene therapeutic applications.
The authors evaluated the responsiveness of 4 preschool-aged children to positive reinforcers within a concurrent operants paradigm during mealtimes. The children were presented with two identical, concurrently available sets of food. Each set differed in quantity and quality of positive reinforcement paired with acceptance of each bite of food or in the number of bites of food required to obtain positive reinforcement. Experiment 1 evaluated 1 child's responsiveness to positive reinforcement while permitting escape from bite offers. Experiment 2 evaluated 2 children's responsiveness to positive reinforcement when escape extinction occurred. Results from these experiments suggested that the children were responsive to positive reinforcers and chose more often the bites paired with the greater quantity and/or quality of reinforcement. Experiment 3 evaluated 1 child's responsiveness to positive reinforcement both without and with escape extinction. Results suggested that positive reinforcement affected choice behavior and that escape extinction affected amount of food consumed.
As the population ages and becomes more frail, pressure ulcer prevalence and incidence within specific care settings are being evaluated through outcomes review. This article summarizes the process and outcomes of an ongoing prevalence study at a 300-bed acute care community hospital. All patients on the adult medical, surgical, and critical care units were examined regularly by the "Rear Admirals," a team comprising a skin care resource person and a nursing unit representative. The Total Quality Management model, characterized by the phrase "Plan-Do-Check-Act," was used to address barriers to quality care. Findings during that time prompted changes in policies, products, protocols, work assignments, and documentation tools. The outcomes achieved demonstrated the effectiveness of those strategies. After implementation of the Total Quality Management model at our Institution, the prevalence of patients with nosocomial pressure ulcers was reduced by 83%.
Plasma apolipoprotein AI (apoAI) and lecithin-cholesterol acyltransferase (LCAT) play important roles in reverse cholesterol transport, promoting the removal of excess cholesterol from peripheral cells and reducing formation of atherosclerotic lesions. Gene augmentation of either apoAI or LCAT, or both, are thus attractive targets for prevention or treatment of atherosclerosis. With the eventual aim of safe and efficient gene delivery to skeletal muscle, our chosen secretory platform for systemic delivery of anti-atherogenic proteins, we have constructed conventional and AAV-based plasmid vectors containing human apoAI or LCAT cDNAs; their efficacy was tested by lipoplex transfection of mouse C2C12 muscle cells or human 293 cells. The secretion of apoAI or LCAT by transduced cultures was two- to five-fold higher using AAV-based plasmid vectors than conventional plasmid vectors. Additionally, cells transfected with a bicistronic AAV-based vector containing an internal ribosome entry site (IRES) efficiently expressed both apoAI and LCAT simultaneously. Furthermore, AAV-based vector sequences were retained by host cells, whereas those of conventional plasmid vectors were lost. These studies indicate that ectopic overexpression of apoAI and LCAT in muscle tissue using AAV-based plasmid vectors might provide a feasible anti-atherogenic strategy in vivo.
Radiographic film is routinely used to obtain dosimetric information about therapy treatment beams. One source of inaccuracy is the variability of the chemical processing of the radiographic film. Several processors, film types and two sources (light and x-rays) were used to investigate the reproducibility of film processing for valid film dosimetry. Particular attention is paid to films commonly used in radiation therapy. The results suggest that for this series of film, given the same exposure, the variability in processing may result in an error of +/- 3.3% in optical density, which would lead to an error of +/- 4.4% in indicated dose. This level of inaccuracy is typical for both point and relative dose estimates. These results indicate that film should not be used as a point or relative dosimeter, unless the combination of film type, exposure, processing and reading have been specifically validated.