Biomedical subjects
Publications and source records attributed to C Jackson.
This paper explores an approach to the implementation and evaluation of integrated health service delivery. It identifies the key issues involved in integration evaluation, provides a framework for assessment and identifies areas for the development of new tools and measures. A proactive role for evaluators in responding to health service reform is advocated.
This trial compared the cost of an integrated home-based care model with traditional inpatient care for acute chronic obstructive pulmonary disease (COPD). 25 patients with acute COPD were randomised to either home or hospital management following request for hospital admission. The acute care at home group costs per separation ($745, CI95% $595-$895, n = 13) were significantly lower (p < 0.01) than the hospital group ($2543, CI95% $1766-$3321, n = 12). There was an improvement in lung function in the hospital-managed group at the Outpatient Department review, decreased anxiety in the Emergency Department in the home-managed group and equal patient satisfaction with care delivery. Acute care at home schemes can substitute for usual hospital care for some patients without adverse effects, and potentially release resources. A funding model that allows adequate resource delivery to the community will be needed if there is a move to devolve acute care to community providers.
BACKGROUND: Urinary incontinence is a common problem but, for those experiencing significant clinical symptoms, help seeking has been reported to be as low as 20%. As many of these people could be helped by simple interventions, there is a clear need to identify barriers to help seeking and develop interventions to overcome these barriers. OBJECTIVES: This study explores help-seeking behaviour in people with urinary symptoms such as leakage, frequency, nocturia and urgency in order to identify barriers to service use. METHOD: Thirty-one people who either had agreed to treatment as part of an intervention study or who were receiving treatment at a hospital out-patient clinic for their urinary problems took part in unstructured, taped interviews. Respondents were questioned about their views on help seeking for urinary problems and their personal experiences of consultations. The data were transcribed, coded and thematic analysis carried out. RESULTS: The most common theme to emerge was a lack of knowledge of the condition and of available treatments. Urinary symptoms frequently were considered a normal part of ageing or childbirth, or it was felt that these types of symptoms were inappropriate for medical intervention. Older people were not only more likely to accept symptoms but were also less likely to want to bother their GP. Patients did not always communicate their concerns about urinary symptoms to their GP, through either embarrassment or misconceptions of what is a 'medical problem'. CONCLUSIONS: There is a clear need for health education and health promotion in this area. Future work should explore professionals' knowledge and views of these types of conditions with the aim of providing guidelines for management in primary care.
Investigation of the pathophysiology of pre-eclampsia (characterised by insufficient invasion of the intrauterine vasculature by cytotrophoblasts) has been hampered by the absence of a suitable animal model, and ethical constraints in clinical studies. We have developed a novel in vitro human cell co-culture system allowing direct assessment of cytotrophoblast invasion of a decidual endothelial cell monolayer from the abluminal side, as occurs in vivo. This model will facilitate detection, at the cellular level, of abnormal endothelial cell-trophoblast functional interactions in pre-eclampsia and other pregnancy disorders with abnormal placentation.
Cytokine networking in the lung in response to inhaled Aspergillus fumigatus was assessed using a murine model of primary pulmonary aspergillosis in immunocompetent Crl:CF-1 mice. Inhalation of virulent A. fumigatus (6 x 10(6) CFU) resulted in the induction of interleukin 18 (IL-18), tumor necrosis factor alpha (TNF-alpha), IL-12, and gamma interferon (IFN-gamma) protein in bronchoalveolar lavage fluid and/or lung tissue. Induction of immunoreactive IL-18 preceded induction of TNF-alpha protein, which preceded induction of immunoreactive IL-12 and IFN-gamma. Real-time reverse transcriptase (RT) PCR analysis of infected lung tissue demonstrated that induction of IL-18 protein also preceded induction of pulmonary TNF-alpha, IL-12, and IFN-gamma mRNAs. Mice were subsequently treated with cytokine-specific neutralizing monoclonal antibodies (MAbs) to the IL-18 receptor (anti-IL-18R MAb), TNF-alpha (anti-TNF-alpha MAb), IL-12 (anti-IL-12 MAb), and/or IFN-gamma (anti-IFN-gamma MAb), and effects on intrapulmonary cytokine activity and growth of A. fumigatus were assessed in infected lung homogenates. Simultaneous neutralization of IL-12 and IL-18 resulted in decreased levels of immunoreactive TNF-alpha, while neutralization of IL-18, TNF-alpha, or IL-12 alone or of IL-18 and IL-12 together resulted in decreased levels of immunoreactive IFN-gamma. Simultaneous neutralization of IL-12 and IL-18 or neutralization of TNF-alpha alone or in combination with IL-12, IL-18, or IFN-gamma also resulted in a significant increase in A. fumigatus CFU in lung tissue. Taken together, these results demonstrate that endogenous IL-18, IL-12, and TNF-alpha, through their modulatory effects on both intrapulmonary cytokine activity and growth of A. fumigatus, play key roles in host defense against primary pulmonary aspergillosis.
Cytokine-mediated host defense against Candida glabrata infection was compared to that against C. albicans, using immunocompetent murine models of systemic candidiasis. The pathogenesis of infection was evaluated morphologically and by culture of target organs, while the kinetics of induction of cytokine mRNAs and corresponding proteins were determined in kidneys by real-time reverse transcription-PCR and cytokine-specific murine enzyme-linked immunosorbent assays, respectively. Systemic infection with C. glabrata resulted in a chronic, nonfatal infection with recovery of organisms from kidneys, while intravenous inoculation with C. albicans resulted in rapid mortality with logarithmic growth of organisms in kidneys and recovery of C. albicans from the spleen, liver, and lungs. Survival of C. glabrata-infected mice was associated with rapid induction of mRNAs and corresponding immunoreactive proteins for the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-12 (IL-12), and gamma interferon (IFN-gamma) and the lack of induction of protein for the anti-inflammatory cytokine IL-10. In contrast, mortality in C. albicans-infected mice was associated with induction of mRNA and corresponding protein for IL-10 but delayed (i.e., TNF-alpha) or absent (i.e., IL-12 and IFN-gamma) induction of immunoreactive proinflammatory cytokines. Mice were subsequently treated with cytokine-specific neutralizing monoclonal antibodies (MAbs) to TNF-alpha, IL-12, or IFN-gamma, and the effect on growth of C. glabrata in kidneys was assessed. Neutralization of endogenous TNF-alpha resulted in a significant increase in C. glabrata organisms compared to similarly infected mice administered an isotype-matched control MAb, while neutralization of endogenous IL-12 or IFN-gamma had no significant effect on C. glabrata replication. These results demonstrate that in response to intravenous inoculation of C. glabrata, immunocompetent mice develop chronic nonfatal renal infections which are associated with rapid induction of the proinflammatory cytokines TNF-alpha, IL-12, and IFN-gamma. Furthermore, TNF-alpha plays a key role in host defense against systemic candidiasis caused by either C. glabrata or C. albicans, as the absence of endogenous TNF-alpha activity was associated with enhanced tissue burden in both infection models.
The effects of a reduction in ambient temperature (from 26 degrees C to 15 degrees C) and a 10% reduction in daily food consumption on reproductively active male and female four-striped field mice ( Rhabdomys pumilio) were investigated. In male R. pumilio, both reduced ambient temperature and a reduction in food quantity had an inhibitory effect on spermatogenesis and on size of the reproductive organs, and this was greatest when the two factors were combined and the effect of fat was removed. Female R. pumilio responded differently and reproduction was inhibited by a reduction in food quantity, irrespective of ambient temperature. The masses of the ovaries and uterus, the numbers of developing follicles and corpora lutea, and the development of the uterine wall were all reduced by food deprivation at 26 degrees C to levels similar to those that resulted from a reduction in ambient temperature to 15 degrees C with a reduction in food quantity. It is concluded that reproduction in R. pumilio from the Eastern Cape Province of South Africa is opportunistic, that reproduction will be inhibited by an energetic challenge and that there is sexual dimorphism in the response to ambient temperature and food supply.
We examined the effect of stabling on upper and lower airway inflammation in 14 yearling Arabian horses that had been at pasture since birth. Horses were divided into 2 groups of 7. One group was stabled for 3 months and the other remained at pasture. The groups were then switched over for another 3 months. The nasopharynx, guttural pouches and trachea were examined endoscopically and bronchoalveolar lavage performed every month. An upper airway inflammation score was devised based on the magnitude of pharyngeal lymphoid hyperplasia and guttural pouch inflammation. During stabling this score remained constant, whereas it decreased during the 3 months at pasture. Stabling was also associated with a higher number and percentage of neutrophils in bronchoalveolar lavage fluid and with a smaller percentage of lymphocytes. There was no correlation between upper airway inflammation score and bronchoalveolar lavage cytology. During a nasal occlusion test, dorsal displacement of the soft palate occurred more times in stabled than in pastured horses, but this was heavily biased by the results from one animal. We conclude that stabling is associated with inflammation of both the upper and lower airway of young horses.
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BACKGROUND: The new '700 series' Medical Benefit Schedule (MBS) items for general practice introduce greatly increased potential for collaboration between general practitioners and other health professionals in patient care. AIM: To investigate the current perceptions of Australian GPs with respect to the desirability and impact of 'sharing care' with nurses and other health professionals. METHOD: Survey of a sample of GPs in Queensland and NSW participating in the Department of Veterans' Affairs Preventive Care Trial. RESULTS: Fifty-two percent of GPs surveyed worked in a practice where a nurse was employed. The main role of the practice nurse was to do electrocardiograms, apply dressings, and triage duties. Practice nurses played only a minor role in health promotion and education. Seventy percent of GPs identified 'cost' and 58% 'lack of a Medicare item' as the major disincentives to the employment of a practice nurse. Seventy percent of GPs were satisfied with the level of communication with community based health professionals outside the practice, with 'time' nominated as the greatest barrier to optimal contact. Eighty-two percent of GPs considered other health professionals had a role in conducting preventive home visits for the older population, with 70% of GPs identifying that these health professionals had the potential to identify additional health problems, previously unaddressed. CONCLUSION: Study findings demonstrate an acceptance by GPs of the nurses role and other health professionals in integrated patient care. Funding is seen as the major impediment to the greater utilisation of practice nurses in the general practice setting.
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The diagnosis of psychogenic nonepileptic seizures (PNES) can only be made with EEG-video monitoring. The authors describe a provocative technique without placebo. Patients with a clinical suspicion for PNES underwent an activation procedure using suggestion, hyperventilation, and photic stimulation. Of 19 inductions performed, 16 (84%) were successful in inducing the habitual episode. The authors' technique had a sensitivity comparable to those using placebo (e.g., saline injection), but does not have disadvantages.
PURPOSE: To test for an association between in vitro fibroblast radiosensitivity and complication risk in a case-control study of breast cancer patients treated under standard conditions in a clinical trial of radiotherapy dose fractionation. PATIENTS AND METHODS: A cohort of patients participating in a randomised clinical trial of radiotherapy dose fractionation was selected on the basis of treatment-induced changes in the breast several years later. Thirty-nine cases with marked normal tissue changes were matched on several variables with 65 controls with no changes attributable to radiotherapy. Dermal fibroblast strains were established from duplicate skin biopsies, and clonogenic cell survival assays performed in triplicate after both high ( approximately 1.6 Gy/min) and low ( approximately 1 cGy/min) dose-rate irradiation. Laboratory studies were blind to patient identity, treatment outcome and radiotherapy schedule. RESULTS: Analysis of 1128 clonogenic survival curves confirmed significant inter-patient variation in fibroblast radiosensitivity as measured by clonogenic survival. However, no association between fibroblast radiosensitivity and the development of late radiotherapy normal tissue effects was detected. CONCLUSIONS: Inter-individual variation in cellular radiosensitivity may not be the main determinant of complication risk in patients undergoing radiotherapy for breast cancer. Other biological and technical factors may be more important in explaining the marked inter-patient differences in normal tissue damage evident several years after curative radiotherapy.
OBJECTIVE: Stereotactic radiation treatment, also known as gamma knife surgery or radiosurgery, has come into acceptance as a treatment alternative to surgical removal for posterior fossa tumors. The purpose of this article is to describe the role of the neurotologist in the optimal management of neurotologic complications after stereotactic radiation, as illustrated by five patients. STUDY DESIGN: Retrospective chart review. PATIENTS: Five patients who underwent stereotactic radiation of posterior fossa tumors. MAIN OUTCOME MEASURES: Presence or absence of neurotologic complications (tumor growth, hearing loss, imbalance/ataxia, vertigo, and facial paralysis) or neurosurgical complaints (facial numbness, motor weakness, headache, hydrocephalus, and subarachnoid cysts). RESULTS: Postradiation neurotologic complaints included vertigo, imbalance/ataxia, and progressive hearing loss in four of the five patients. Continued tumor growth occurred in two patients; two patients had no growth; in one patient the tumor became smaller. The complications of facial nerve paralysis, facial numbness, motor weakness, headache, hydrocephalus, cerebellar edema, and posterior fossa arachnoid cyst formation occurred less frequently. CONCLUSIONS: Stereotactic radiation of posterior fossa tumors can produce significant neurotologic problems. It is imperative that neurotologists remain involved in the follow-up care of patients with posterior fossa tumors to offer optimal treatment alternatives for the neurotologic disorders.
This qualitative study was undertaken to assess patients' views of the urodynamic investigation. The aim was to identify the dimensions important to patients in evaluating satisfaction with this type of procedure and ways in which care could be improved. Unstructured interviews were carried out by four trained interviewers with 21 people (17 female and 4 male) who had undergone the urodynamic investigation at various gynaecology, urology and continence outpatient clinics. The interviews were audio-taped and transcribed verbatim. The data was then coded and a thematic analysis carried out. The main theme to emerge was focused on patients' feelings about the procedure. This consisted of a combination of anxiety and embarrassment. Anxiety was because of fear of the unknown and embarrassment at the intimate nature of the procedure and lack of privacy. The interpersonal and communication skills of the health care professional were central in alleviating these negative feelings. The establishment of a friendly relationship based on equality and mutual respect and trust was important in preventing anxiety and embarrassment. A number of practical issues were identified that would contribute to improving the service for patients. It was found that nurses possessed all the attributes required to provide an effective service and recommendations were made that nurses specializing in continence care should take a more active role in urodynamic investigations.
PURPOSE: Little formal eye skills training has historically been available to Australian general practitioners at undergraduate or postgraduate levels. The development of the National GP Eye Skills Workshop was a joint initiatve of the Royal Australian Colleges of General Practice and Ophthalmology, to enhance the skills of Australian general practitioners in a range of important ocular examination and procedural areas. METHODS: Workshops were run in eight Queensland Divisions of General Practice in 1998. Between two and 10 local ophthalmologists in each divisional area were involved ether in the workshop programme or in the recruitment of patients for the patient assessment module. Workshops were run on weekends and included modules on vision testing and disease screening in children and adults, ophthalmoscopy, assessment for glaucoma and diabetic retinopathy, incision of chalazions, removal of corneal foreign bodies, ocular first aid, implementing eye assessment in busy general practice, and a patient assessment clinic. A questionnaire was administered which was comprised of sections relating to the format of the workshop, new skills and concepts learnt, learning exceptions, and perception of future ability to treat/scan/assess for eye conditions in general practice. The questionnaire was completed by 91% of participants. RESULTS: Participants strongly supported the impact of the workshop on their ability to detect and treat eye problems in their practices, and refer where appropriate to an ophthalmologist. They also rated highly all individual aspects of the programme in terms of impact on their delivery of general practitioner eye care. CONCLUSIONS: The results illustrate the comprehensive success of the workshop programme in format, content, relevance and delivery.
The in vivo role of endogenous interleukin-18 (IL-18) in modulating gamma interferon (IFN-gamma)-mediated resolution of replicative Legionella pneumophila lung infection was assessed using a murine model of Legionnaires' disease. Intratracheal inoculation of A/J mice with virulent bacteria (10(6) L. pneumophila organisms per mouse) resulted in induction of IL-18 protein in bronchoalveolar lavage fluid (BALF) and intrapulmonary expression of IL-18 mRNA. Real-time quantitative RT-PCR analysis of infected lung tissue demonstrated that induction of IL-18 in BALF preceded induction of IL-12 and IFN-gamma mRNAs in the lung. Blocking intrapulmonary IL-18 activity by administration of a monoclonal antibody (MAb) to the IL-18 receptor (anti-IL-18R MAb) prior to L. pneumophila infection inhibited induction of intrapulmonary IFN-gamma production but did not significantly alter resolution of replicative L. pneumophila lung infection. In contrast, blocking endogenous IL-12 activity by administration of anti-IL-12 MAb) alone or in combination with anti-IL-18R MAb inhibited induction of intrapulmonary IFN-gamma and resulted in enhanced intrapulmonary growth of the bacteria within 5 days postinfection. Taken together, these results demonstrate that IL-18 plays a key role in modulating induction of IFN-gamma in the lung in response to L. pneumophila and that together with IL-12, IL-18 regulates intrapulmonary growth of the bacteria.
Porphyromonas gingivalis is a gram-negative, anaerobic coccobacillus that has been implicated as a major etiological agent in the development of chronic periodontitis. In this paper, we report the characterization of a protein, IhtB (iron heme transport; formerly designated Pga30), that is an outer membrane hemin-binding protein potentially involved in iron assimilation by P. gingivalis. IhtB was localized to the cell surface of P. gingivalis by Western blot analysis of a Sarkosyl-insoluble outer membrane preparation and by immunocytochemical staining of whole cells using IhtB peptide-specific antisera. The protein, released from the cell surface, was shown to bind to hemin using hemin-agarose. The growth of heme-limited, but not heme-replete, P. gingivalis cells was inhibited by preincubation with IhtB peptide-specific antisera. The ihtB gene was located between an open reading frame encoding a putative TonB-linked outer membrane receptor and three open reading frames that have sequence similarity to ATP binding cassette transport system operons in other bacteria. Analysis of the deduced amino acid sequence of IhtB showed significant similarity to the Salmonella typhimurium protein CbiK, a cobalt chelatase that is structurally related to the ATP-independent family of ferrochelatases. Molecular modeling indicated that the IhtB amino acid sequence could be threaded onto the CbiK fold with the IhtB structural model containing the active-site residues critical for chelatase activity. These results suggest that IhtB is a peripheral outer membrane chelatase that may remove iron from heme prior to uptake by P. gingivalis.