Audiotaping the heart surgery consultation: qualitative study of patients' experiences.
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Communication↗
Biomedical subjects
J Douglass
Publications and source records attributed to J Douglass.
Proteases and pH in chronic wounds.
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Bandages↗
Enhancing validity: what counts as an asthma attack?
BACKGROUND: Major epidemiological studies in asthma use the question: "How many attacks of asthma have you had in the last 12 months?" We set out to study what constitutes an asthma attack from the perspective of people with asthma. We also examined concordance between qualitative responses and standard quantitative measures of this question. METHODS: Individuals aged 18 to 70 years who sought care for asthma at Emergency Departments in an Australian central city, a suburban and a regional hospital were recruited. Sixty two (43 women and 19 men) participants were interviewed in depth. All interviews were taped, transcribed and thematically analyzed. Demographic data and responses to respiratory health data were also collected. FINDINGS: Widely varying responses to the question, "How many attacks of asthma have you had in the last 12 months?" were found in the quantitative data set. Comparison of quantitative and qualitative data sets showed good agreement between these two responses (intraclass correlation 0.66). People defined asthma attacks as "major" and "minor," as determined by the degree of personal control they were able to exercise. A strongly unifying description of a severe attack was that it was "out of control." Patient's recognized that upper respiratory tract infections commonly triggered major attacks. INTERPRETATION: A commonly asked question about the number of asthma attacks in the past year needs refinement in order to enhance validity. Asthma action plans should use the words "out of control" when defining a severe attack of asthma.
Adolescent↗
Choosing to attend an asthma doctor: a qualitative study in adults attending emergency departments.
BACKGROUND: Asthma treatment guidelines currently recommend a 'therapeutic partnership' to achieve best care. It is frequently assumed that individuals presenting to emergency departments with asthma do not have a good doctor-patient relationship. We asked what is the nature of patients' relationships with their doctors in those presenting to hospital emergency departments for asthma care. METHODS: A qualitative study of all consenting individuals aged 18-70 years who presented to a hospital emergency department over 2 months was carried out. Sixty-two participants (19 male) engaged in in-depth interviews which were taped, transcribed and underwent thematic analysis. Questionnaire data were also collected and asthma severity determined. RESULTS: Nearly all patients (61/62) had a doctor whom they saw for their asthma. Patients made thoughtful choices on where they sought care according to their needs. Our findings identified that perceptions of doctors' competence, listening to patients and time constraints were important influences on doctor-patient relationships. Participants had strong expectations that their personal disease experience would be acknowledged by their doctors. CONCLUSION: This group of patients had doctors who cared for their asthma. The acceptability of medical care was determined as much by patient choice as by the quality of the doctor-patient relationship.
Adolescent↗
Role of intravenous immunoglobulin in severe steroid-dependent asthma.
BACKGROUND: Subgroups of asthma patients have extremely severe respiratory symptoms that require chronic use of steroids for disease control. These patients are at risk of significant side-effects from chronic exposure to high doses of oral steroids. Intravenous immunoglobulin (IVIG) has immunomodulatory properties as shown by its use in some immune disorders. A few trials have suggested a possible benefit in individuals with severe asthma. AIMS: To evaluate the role of IVIG as an adjunctive therapy in steroid-dependent asthma, monitoring the outcomes of lung function and measured reduction in oral steroid requirement. METHOD: Seven patients with severe steroid-dependent asthma were given IVIG at a dose of 1 g/kg each month for 6 months. Baseline pulmonary function tests and immunoglobulin levels were obtained. At the end of 6 months, the end-points observed were lung function and the degree of reduction in the dose of oral steroids. The number of hospital admissions during the 12 months following commencement of IVIG was compared with the preceding 12 months. RESULTS: There was a significant reduction in daily prednisolone dose from 56 +/- 31 mg to 39 +/- 35 mg (P=0.04, Wilcoxon rank sum test) and a decrease in the number of hospital admissions from 5.9 +/- 2.9 to 3.6 +/- 3.5 (P=0.04). No significant improvement occurred in lung function. CONCLUSION: IVIG provides a potentially important adjunctive therapy in severe steroid-dependent asthma, reducing steroid requirement and decreasing hospital admissions, but not improving lung function.
Adjuvants, Immunologic↗
Specific allergen immunotherapy: time for alternatives?
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Administration, Intranasal↗
Effects of diadenosine polyphosphates on tear secretion in New Zealand white rabbits.
Extracellular diadenosine polyphosphates play important signaling functions in a number of physiological responses. Here we show that diadenosine polyphosphates are normal constituents of tear fluid and are potent stimulators of tear secretion through their interaction with P2Y receptors. Diadenosine tetraphosphate (Ap(4)A) and Ap(5)A were found in rabbit tears under basal conditions at concentrations of 2.92 and 0.58 microM, respectively. Single applications of UTP, ATP, and Ap(4)A increased tear secretion to 160 +/- 8% (n = 16) (P < 0.001), 131 +/- 6% (P < 0.05), and 162 +/- 11% (P < 0.05) of placebo values, respectively. Ap(4)A, Ap(5)A, and Ap(6)A, but not Ap(2)A and Ap(3)A, were able to stimulate tear secretion in a dose-dependent manner. Concentration-response studies produced pD(2) values of 5.56 +/- 0.03, 5.75 +/- 0.12, and 5.50 +/- 0.09 for Ap(4)A, Ap(5)A, and Ap(6)A, respectively, with Ap(4)A showing the greatest efficacy. Diadenosine polyphosphates also stimulated P2Y(1) and P2Y(2) receptors expressed in 1321N1 cells with no apparent effect on the other P2Y receptors tested. Nonselective P2 antagonists did not modify the tear secretion induced by UTP or Ap(4)A in rabbit eyes in vivo or in cloned receptors, except for a weak but significant reduction in stimulated tear secretion by reactive blue 2. These results suggest that diadenosine polyphosphates stimulate tear secretion via a P2Y receptor-mediated mechanism. Comparing the effects of diadenosine polyphosphates applied to the rabbit eye and to cloned P2Y receptors, it appears that the P2Y(2) receptor subtype is responsible for the prosecretory effects of these compounds.
Adenine Nucleotides↗
Identification of incompletely processed potential carboxypeptidase E substrates from CpEfat/CpEfat mice.
In an attempt to identify peptides that may be involved in the obese phenotype observed in CpEfat/CpEfat mice (deficient in Carboxypeptidase E, CpE) samples from fourteen neuroendocrine tissues in wild-type and CpEfat/CpEfat mice were obtained. Peptides were purified from these tissues and potential CpE substrate peptides were enriched using an anhydrotrypsin column that captures peptides with basic C-termini. Bound peptides were subjected to tryptic digestion and followed by liquid chromatography-mass spectrometry analysis. The relative levels of CpEfat/CpEfat versus wild-type peptides were determined by comparison of the ion intensities. Peptide ions elevated in the CpEfat/CpEfat samples were identified by targeted liquid chromatography-tandem mass spectrometry. From those ions, 27 peptides derived from known neuropeptides (including CpE substrates) were identified, together with another 25 peptides from proteins not known to be components of the neuropeptide processing pathway. The known CpE substrates identified included the recently discovered proSAAS, granin-like neuroendocrine peptide precursor that inhibits prohormone processing. The approach demonstrated the feasibility of using an affinity-based method for identifying differences in specific classes of peptides between normal and mutant mice.
Amino Acid Sequence↗
Multiple behavioral effects of cocaine- and amphetamine-regulated transcript (CART) peptides in mice: CART 42-89 and CART 49-89 differ in potency and activity.
Cocaine- and amphetamine-regulated transcript (CART) encodes a neuropeptide precursor protein that is highly abundant in cells of the hypothalamus. To date, the major research focus into the function of CART peptides has been feeding behavior. However, CART mRNA is found in other areas of the brain as well as some peripheral tissues, suggesting possible broader functions of this peptide. In this study, we investigated the effects of two CART peptides, CART 42-89 and CART 49-89, in several behavioral assays. Peptides were administered by i.c.v. route of administration. Both CART 42-89 and CART 49-89 inhibited food intake with the minimally effective dose of CART 42-89 (0.5 microg) being 5-fold greater than that of CART 49-89 (0.1 microg). Both peptides also produced significant antinociceptive effects in the hot-plate assay with similar potency differences. CART 42-89 significantly inhibited the acoustic startle response (ASR) of pulse alone trials at doses of 0.1 and 0.5 microg. In contrast, CART 49-89 did not affect ASR of pulse alone trials at doses of 0.05 and 0.1 (microg). For prepulse inhibition (PPI) trials, in general, both peptides appeared to enhance the magnitude of PPI and CART 42-89 was less potent than CART 49-89. Overall, these data suggest CART peptides may have multiple roles in central nervous system function and there may be biological differences between two processed forms of CART peptide.
Acoustic Stimulation↗
Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing.
Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These peptides are produced from a single precursor, termed proSAAS, which is present in human, mouse, and rat. ProSAAS mRNA is expressed primarily in brain and other neuroendocrine tissues (pituitary, adrenal, pancreas); within brain, the mRNA is broadly distributed among neurons. When expressed in AtT-20 cells, proSAAS is secreted via the regulated pathway and is also processed at paired-basic cleavage sites into smaller peptides. Overexpression of proSAAS in the AtT-20 cells substantially reduces the rate of processing of the endogenous prohormone proopiomelanocortin. Purified proSAAS inhibits prohormone convertase 1 activity with an IC(50) of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.
Adrenal Glands↗
Allergen immunotherapy: current and new therapeutic strategies.
Allergic individuals respond to an environmental allergen encounter by producing T-cell cytokines, predominantly IL-4 and IL-5, which in turn drive the production of allergen-specific IgE antibodies and recruitment of an eosinophil-rich inflammatory infiltrate. Allergen-specific immunotherapy (SIT) involves the repeated injection of the allergen to specifically downregulate this predominantly Th2-type immune response. SIT is a clinically proven effective treatment for allergic diseases, including rhinoconjunctivitis and asthma. However, despite having been in clinical practice since early this century, its use remains empirical. Best practice protocols are based on clinical experience and include recommendations for selecting patients for treatment, SIT regimes and avoidance of adverse events. More rational and safer SIT regimes will result from new insights into the underlying immune mechanisms for allergic disease, in particular the critical role of helper T-cells in orchestrating this response. The development of recombinant techniques for producing purified allergens and allergen derivatives has led to a dramatic improvement in the ability to standardise allergen preparations and to develop novel vaccines for allergy treatment. Potential vaccines include short peptides based on dominant T-cell epitopes of allergens, allergen fragments and mutant allergens. All of these preparations are designed to target T-cells without binding IgE and inducing local and systemic side effects. Additional strategies under consideration include DNA vaccines and fusion protein constructs incorporating immunomodulatory elements such as bacterial cell proteins, cytokines and immunostimulatory sequences of DNA. Different forms of allergens are being evaluated for the more practical mucosal administration of allergy vaccines. The identification of recombinant allergens suitable for diagnostic use and the development of reliable laboratory assays, based on T-cell function to monitor clinical efficacy of SIT, are important practical outcomes from this research.
Allergens↗
Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease.
The treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential use for immunotherapy against PTLD in solid organ transplant patients. Peripheral blood mononuclear cells from a panel of solid organ transplant recipients with and without active PTLD were used to assess EBV-specific memory CTL responses. The activation protocol involved cocultivation of peripheral blood mononuclear cells with an autologous lymphoblastoid cell line under conditions that favored expansion of virus-specific CTL and hindered the proliferation of allospecific T cells. These CTL consistently showed (i) strong EBV-specificity, including reactivity through defined epitopes in spite of concurrent immunosuppressive therapy, and (ii) no alloreactivity toward donor alloantigens. More importantly, adoptive transfer of these autologous CTLs into a single patient with active PTLD was coincident with a very significant regression of the PTLD. These results demonstrate that a potent EBV-specific memory response can be expanded from solid organ recipients who have acquired their primary EBV infection under high levels of immunosuppressive therapy and that these T cells may have therapeutic potential against PTLD.
Adoptive Transfer↗
Evidence of a specific pancreatic polypeptide receptor in rat arterial smooth muscle.
Pancreatic polypeptide (PP) is a member of the PP fold family of regulatory peptides. Studies have shown that neuropeptide Y, peptide YY, and PP increased gastrointestinal motility. The GI effects of neuropeptide Y and peptide YY were accompanied by an increase in mean arterial blood pressure; however, PP decreased mean arterial blood pressure. Cloning of a receptor of the neuropeptide Y family with high affinity for PP has been reported. This Y4 receptor is present in intestine, pancreas, and prostate, and its mRNA has been detected in brain and coronary artery. We found in vitro evidence of PP-mediated inhibition of arterial neurogenic vasoconstriction. We have also detected Y4 mRNA in rat peripheral arteries. These findings suggest a potential role for the Y4 receptor in regulating vascular tone.
Animals↗
Allergy in the airway.
BACKGROUND: Airway disease is responsible for significant morbidity worldwide and the role of allergies in the cause and persistence of airway symptoms is becoming increasingly appreciated. OBJECTIVE: The exposure of the airway to allergens depends on the size of inhaled particles. Common allergens encountered in Australia include grass pollens, house dust mites and animal danders and sensitivity to each leads to a different clinical pattern of disease. The diagnosis of allergy requires a history of symptoms related to exposure to an allergen, together with detection of allergen-specific IgE. The evidence for the role of allergens in contributing to allergic airway disease is extensive. DISCUSSION: Airway allergies are an important factor in the genesis of asthma and allergic rhinitis. There is increasing evidence that modification of exposure to allergens can improve allergic symptoms and may prevent allergic diseases. Methods of allergen avoidance are discussed.
Allergens↗
Stinging insect allergies. Assessing and managing.
BACKGROUND: Mortality secondary to insect sting anaphylaxis, though uncommon in this country, is a genuine risk to patients with venom hypersensitivity. A number of non specific and specific preventive measures are available to minimise this risk. They include proper patient counselling regarding sting avoidance and the use of self injectable adrenaline, as well as venom specific immunotherapy. OBJECTIVE: This article attempts to review the spectrum of insect sting reactions, their appropriate assessment and subsequent management. Anaphylaxis is particularly emphasised with regard to first aid treatment and subsequent prevention. DISCUSSION: The most common causes of insect stings in Australia are bees and wasps. Insect sting reactions cover a spectrum of responses, from normal to anaphylactic. Immunotherapy is indicated in those patients who experience anaphylactic responses. The presence of venom specific IgE must be demonstrated before commencing immunotherapy. Venom sensitive patients should be educated in anaphylaxis first aid with adrenaline self injectable syringes.
Adrenergic Agonists↗
Characterization of the human cDNA and genomic DNA encoding CART: a cocaine- and amphetamine-regulated transcript.
PCR differential display screening has recently identified a rat mRNA termed CART (cocaine- and amphetamine-regulated transcript) which is transcriptionally regulated in the striatum following acute administration of psychomotor stimulants. The endogenous CART transcript is expressed in diverse rat brain structures, as well as endocrine tissues. The deduced CART protein contains a hydrophobic signal sequence, suggesting that it may be targeted for secretion. Thus, the CART protein may represent a novel neuroendocrine signaling molecule. The study described here represents a complete analysis of the human CART cDNA and gene. The complete nucleotide (nt) sequence of the approx. 900-nt human CART transcript is contained within three distinct exons, with the entire human CART gene localized to a segment of genomic DNA approx. 2 kb in length. The human CART cDNA sequence is 80% identical to the corresponding rat cDNA, with 92% homology observed within the deduced protein-coding region. Third-nt changes account for most of the latter differences, with CART exhibiting 95% identity between these two species at the amino-acid sequence level. PCR/Southern blot analysis of DNA isolated from human/rodent somatic cell hybrid panels localizes the CART gene to human chromosome 5. Lastly, Northern blot analysis reveals that the gross pattern of distribution of CART mRNA in human brain is similar to that previously observed in rat. These overall similarities suggest that CART plays a conserved role within the mammalian neuroendocrine system.
Amino Acid Sequence↗
Intradermal challenge with interleukin-8 causes tissue oedema and neutrophil accumulation in atopic and non-atopic human subjects.
BACKGROUND: Interleukin-8 (IL-8) is a cytokine with potent neutrophil chemotactic and activating properties and is active in inflammatory conditions in man. It has been identified in human inflammatory skin conditions where it is likely to be responsible for both neutrophil recruitment from the circulation and possibly T-lymphocyte chemoattraction. Studies in animals also suggest that IL-8 may augment skin oedema. OBJECTIVE: To study the effects of intradermally administered IL-8 in humans on tissue oedema and cellular recruitment in atopic and non-atopic volunteers. METHOD: Interleukin-8 (1.2 x 10(-7) M) in the presence and absence of histamine was administered by intradermal injection. Wheal and erythema area were measured at regular intervals and 3 h following challenge punch biopsies were taken for immunocytochemistry. Cellular infiltrate was measured by immunocytochemical identification of neutrophils, eosinophils and T-lymphocytes in glycol-methacrylate-embedded sections. RESULTS: In the presence of histamine, IL-8 provoked a significantly greater wheal area when compared to that produced by histamine alone (P < 0.001). In the presence of histamine, IL-8 produced a significantly greater neutrophil infiltrate (P < 0.05), however, neither lymphocyte or eosinophil infiltration was found to be increased with IL-8 challenge. There was no difference observed between atopic and non-atopic subjects, nor were any effects of IL-8 demonstrated in the absence of histamine. CONCLUSION: This study demonstrates that in human skin, IL-8 induces increased microvascular permeability and neutrophil infiltration, but not eosinophil or T-lymphocyte chemoattraction.
Adolescent↗
Neuronal adaptation to amphetamine and dopamine: molecular mechanisms of prodynorphin gene regulation in rat striatum.
Induction of prodynorphin gene expression by psychostimulant drugs may represent a compensatory adaptation to excessive dopamine stimulation and may contribute to the aversive aspects of withdrawal. We therefore investigated the molecular mechanisms by which dopamine psychostimulant drugs induce prodynorphin gene expression in vivo and in rat primary striatal cultures. We demonstrate that three recently described cAMP response elements (CREs), rather than a previously reported noncanonical AP-1 site, are critical for dopamine induction of the prodynorphin gene in striatal neurons. CRE-binding protein (CREB) binds to these CREs in striatal cell extracts and is phosphorylated on Ser-133 after dopamine stimulation in a D1 dopamine receptor-dependent manner. Surprisingly, following chronic administration of amphetamine, levels of phosphorylated CREB are increased above basal in rat striatum in vivo, whereas c-fos mRNA is suppressed below basal levels. D1 receptor-mediated CREB phosphorylation appears to mediate adaptations to psychostimulant drugs in the striatum.
Amphetamine↗