A randomised crossover trial of chemotherapy in the home: patient preferences and cost analysis.
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Biomedical subjects
Publications and source records attributed to J P Hall.
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In Australia, demographic changes have seen the population of large cities move away from the inner city. This, combined with changes in healthcare delivery and the ageing of many tertiary teaching hospitals, has led governments to attempt to close, relocate or redefine the role of some institutions. Tracing the media coverage of two such events--the attempts to move St Vincent's hospitals in Sydney and Melbourne--provides some interesting insights into the challenges of resource allocation facing policymakers within the healthcare sector. Both hospitals were long-established, much-loved fixtures on inner-city sites with powerful connections to government and business. In Sydney, where the attempt was part of a larger plan to reallocate resources to the western suburbs, the announcement was met with 10 days of intense media coverage and scrutiny by lobby groups and the general public. By contrast, in Melbourne, no such announcement was made and the low-key reporting of support and opposition to the move occurred over two months. Both attempts failed. No matter how the debate is handled, radical changes involving long-established hospitals, powerful provider groups and loyal communities are very difficult to accomplish.
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Cationic chalcogenopyrylium dyes 5 were synthesized in six steps from p-aminophenylacetylene (9), have absorption maxima in methanol of 623, 654, and 680 nm for thio-, seleno-, and telluropyrylium dyes, respectively, and generate singlet oxygen with quantum yields [Phi((1)O(2))] of 0.013, 0.029, and 0.030, respectively. Selenopyrylium dye 5-Se was phototoxic to cultured murine Colo-26 and Molt-4 cells. Initial acute toxicity studies in vivo demonstrate that, at 29 mg (62 micromol)/kg, no toxicity was observed with 5-Se in animals followed for 90 days under normal vivarium conditions. In animals given 10 mg/kg of 5-Se via intravenous injection, 2-8 nmol of 5-Se/g of tumor was found at 3, 6, and 24 h postinjection. Animals bearing R3230AC rat mammary adenocarcinomas were treated with 10 mg/kg of 5-Se via tail-vein injection and with 720 J cm(-2) of 570-750-nm light from a filtered tungsten lamp at 200 mW cm(-2) (24 h postinjection of 5-Se). Treated animals gave a tumor-doubling time of 9 +/- 4 days, which is a 300% increase in tumor-doubling time relative to the 3 +/- 2 days for untreated dark controls. Mechanistically, the mitochondria appear to be a target. In cultured R3230AC rat mammary adenocarcinoma cells treated with 0.1 and 1.0 microM 5-Se and light, mitochondrial cytochrome c oxidase activity was inhibited relative to cytochrome c oxidase activity in untreated cells. Irradiation of isolated mitochondrial suspensions treated with 10 microM dye 5-Se inhibited cytochrome c oxidase activity. The degree of enzyme inhibition was abated in a reduced oxygen environment. Superoxide dismutase, at a final concentration of 30 U, did not alter the photosensitized inhibition of mitochondrial cytochrome c oxidase by dye 5-Se. The data suggest that singlet oxygen may play a major role in the photosensitized inhibition of mitochondrial cytochrome c oxidase.
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Transplantation of microencapsulated islets of Langerhans is impaired by a pericapsular host reaction that eventually induces graft failure. We are studying the role of cytokines in the pathogenesis of this reaction, using the model of alginate-polylysine microcapsule implantation in rat epididymal fat pads. The objectives were: (1) to develop a method to measure, by semiquantitative PCR, TGF-beta1 gene expression in fat pad pericapsular infiltrates, and (2) to use this method to evaluate TGF-beta1 gene expression 14 days after microcapsule implantation. TGF-beta1 mRNA level was significantly higher in pericapsular infiltrate cells than in nonimplanted tissue cells and saline-injected tissue cells (p < 0.0001 and p < 0.01, respectively). There was no significant difference between the TGF-beta1 mRNA levels of the two types of controls (p = 0.0945). These results suggest that TGF-beta1 plays a role in the pathogenesis of the pericapsular reaction. The method developed can be used to study the role of other fibrogenic cytokines potentially involved. This will shed light on the mechanisms underlying the pericapsular reaction and will serve as a basis for the development of strategies to control this reaction.
Mitogen-activated protein (MAP) kinase cascades are conserved signal transduction pathways that are required for eukaryotic cells to respond to a variety of stimuli. Multiple MAP kinase pathways can function within a single cell type; therefore, mechanisms that insulate one MAP kinase pathway from adventitious activations by parallel pathways may exist. We have studied interactions between the mating pheromone response and the osmoregulatory (high-osmolarity glycerol response [HOG]) pathways in Saccharomyces cerevisiae which utilize the MAP kinases Fus3p and Hog1p, respectively. Inactivating mutations in HOG pathway kinases cause an increase in the phosphotyrosine content of Fus3p, greater expression of pheromone-responsive genes, and increased sensitivity to growth arrest by pheromone. Therefore, the HOG pathway represses mating pathway activity. In a HOG1+ strain, Fus3p phosphotyrosine increases modestly and transiently following an increase in the extracellular osmolarity; however, it increases to a greater extent and for a sustained duration in a hog1-delta strain. Thus, the HOG-mediated repression of mating pathway activity may insulate the mating pathway from activation by osmotic stress. A FUS3 allele whose gene product is resistant to the HOG-mediated repression of its phosphotyrosine content has been isolated. This mutant encodes an amino acid substitution in the highly conserved DPXDEP motif in subdomain XI. Other investigators have shown that the corresponding amino acid is also mutated in a gain-of-function allele of the MAP kinase encoded by the rolled locus in Drosophila melanogaster. These data suggest that the DPXDEP motif plays a role in the negative regulation of MAP kinases.
Mitogen-activated protein (MAP) kinases comprise a family of conserved, eukaryotic enzymes that mediate responses to a wide variety of extracellular stimuli. In yeast, different signal transduction pathways utilize distinct MAP kinase family members. We have identified a new yeast MAP kinase gene (named SMK1) that is required for the completion of sporulation. Molecular and cytologic markers indicate that meiotic development proceeds normally in homozygous smk1-delta 1 diploids through meiosis II. However, light and electron microscopy show that smk1 asci are defective in organizing spore wall assembly. Consistent with a defect in spore wall assembly, smk1-delta 1 mutant asci display enhanced sensitivities to enzymatic digestion, heat shock, and exposure to ether. SMK1 mRNA, which is not detectable in vegetative cells, is derepressed at least 200-fold just prior to prospore enclosure. We propose that the SMK1 MAP kinase participates in a developmentally regulated signal transduction pathway that coordinates cytodifferentiation events with the transcriptional program.
The identification of risk factors, such as a raised cholesterol level, hypertension, cigarette smoking, and obesity, permits the prediction of the possible development of ischaemic heart disease and has led to attempts at its prevention through modification of these factors. A high risk of developing ischaemic heart disease is also associated with age, specific socioeconomic groups, a family history of ischaemic heart disease, and preexisting evidence of the disease. Preventive strategies have either sought to reduce the average levels of risk in the general population or to identify by population screening individuals or groups who are at particular risk and to reduce their level of risk. Differing methods of risk-factor identification and modification are appropriate for each of the high-risk groups. For a number of strategies that are directed at either the whole population or high-risk groups we have estimated the costs of identification and risk-factor modification and the probable benefits of undertaking such a strategy. A strategy which educates the whole population by way of the media costs considerably less than does any strategy that involves the identification of individuals at high risk. At a medium cost estimate, with a reduction in risk of only 1%, such an approach costs approximately $8000 per case that is prevented; when risk reduction approaches 3% it actually results in a saving of health-care expenditure within five years. The costs of the other strategies vary between $12,000 and $26,000 per case that is prevented in a five-year period.
Progress in health promotion and preventive programme planning is limited by a lack of data on the development of current activities. A cross sectional survey of hospitals, community health centres, and other health agencies in New South Wales was therefore undertaken to determine the nature and extent of health promotion programmes being conducted in the period July to December 1983. A subsample of 1198 preventive programmes in child and family health was identified, making up 26% of all programmes operating in this period. Results indicate that three major types of programme are being conducted in child health. These are in the areas of (1) parent education and support, (2) school health education, including drug and alcohol education and personal development, and (3) child safety and first aid. Although the nature of these programmes generally corresponds with current thinking on what priorities in health promotion should be, results also indicate that evaluation of these programmes is limited. Most programmes assess only what participants think of the programme rather than assessing changes in knowledge, attitude, behaviour, or health status. Improvements in evaluation practice are required if preventive intervention programmes are to undertake seriously the task of altering the pattern of diseases and problems in childhood and adolescence.
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Respiratory emergencies are a challenge, both to the patient's life and to the nurse who must deal with the emergency. Regardless of the initiating event, the patient must be assessed and treatment instituted rapidly. Clearing of the airway and breathing are the first two considerations for action in the emergency department's protocol, and in many cases it will be the sole responsibility of the nurse to facilitate these essential functions.
The X-ray crystal structure of [Ru3 O2 (NH3)14] (S2 O3)3 . 4H2 O, the thiosulphate salt of Ruthenium Red, has been determined. The cation contains an essentially linear N-Ru-O-Ru-O-Ru-N backbone formed from three ruthenium coordination octahedra, giving an effectively cylindrical shape to the ion. Resonance Raman spectra are consistent with retention of this structure in solution.
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