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Biomedical subjects

J R Butler

Publications and source records attributed to J R Butler.

At least 19 recordsLinked to original sources
PubMed2001

Meningococcal vaccination for adolescents? An economic evaluation in Victoria.

OBJECTIVE: To undertake an economic evaluation of the options for vaccination of adolescents using meningococcal polysaccharide vaccine based on Victorian data. METHODOLOGY: Cost-effectiveness and cost-benefit analyses of three options for vaccination were undertaken for hypothetical populations aged 15-19 years. Baseline analyses assumed a single year of programme implementation and vaccine protection of 5 years. Sensitivity analyses of key variables were performed. Outcomes included the number of people vaccinated, cases averted, life years saved and disability adjusted life years (DALY) averted. Lost earnings avoided were included as a measure of vaccination benefit in cost-benefit analyses. RESULTS: Vaccination of people in Years 10-12 (secondary school) and first year university within a defined population with a high rate of disease was the most cost-effective option. Excluding direct cost savings and compared with no vaccination, this resulted in a discounted cost per DALY avoided of $17646 and benefits exceeding costs in discounted terms. The 'break-even' incidence rate for this option in the cost-benefit analysis was 11.9/100000. CONCLUSIONS: Economic evidence favours the use of vaccination within well-defined populations with a high rate of disease.

Adolescent↗
PubMed2001

Should programmes for community-level meningococcal vaccination be considered in Australia? An economic evaluation.

BACKGROUND: Disease due to serogroup C Neisseria meningitidis is life-threatening and potentially preventable by vaccination. In 1999, the UK instigated mass vaccination after a sustained increase in serogroup C meningococcal disease. In the same year, Victoria, Australia experienced a similar change in disease epidemiology. It is timely to undertake an economic evaluation of options for community vaccination in Australia based on local data. METHODS: Cost-effectiveness and cost-benefit analyses of three options for use of polysaccharide vaccine were undertaken for a hypothetical population aged 15--19 years. Baseline analyses assumed 5 years' duration of vaccine protection following a single year of programme implementation. Sensitivity analyses of key variables were performed, including vaccine coverage and effectiveness, case fatality rate and the discount rate. Outcomes included the number of people vaccinated, cases averted, life-years saved and disability-adjusted life-years (DALY) averted. Cost-benefit analysis used lost earnings avoided as a measure of vaccination benefit. RESULTS: Vaccination of people aged 15--19 years in a defined population with a high rate of disease was the most cost-effective option. Compared with no vaccination and assuming 5 years' duration of protection and exclusion of direct cost savings, this resulted in a discounted cost per life-year saved of $23,623, a cost per DALY avoided of $21,097 and benefits exceeding costs in discounted terms. The 'break-even' incidence rate for this option with exclusion of direct cost savings was 14.0/100,000. CONCLUSIONS: Community use of polysaccharide vaccination may be cost effective in Australia under certain conditions. Economic evidence favours use of vaccination in well-defined populations with a high rate of disease. Policy decision-making also requires consideration of non-economic factors, including feasibility of implementation and risk perception by the community.

Adolescent↗
PubMed2000

Deficiency of Src homology 2-containing phosphatase 1 results in abnormalities in murine neutrophil function: studies in motheaten mice.

Neutrophils, an essential component of the innate immune system, are regulated in part by signaling pathways involving protein tyrosine phosphorylation. While protein tyrosine kinase functions in regulating neutrophil behavior have been extensively investigated, little is known about the role for specific protein tyrosine phosphatases (PTP) in modulating neutrophil signaling cascades. A key role for Src homology 2 domain-containing phosphatase 1 (SHP-1), a PTP, in neutrophil physiology is, however, implied by the overexpansion and inappropriate activation of granulocyte populations in SHP-1-deficient motheaten (me/me) and motheaten viable (me(v)/me(v)) mice. To directly investigate the importance of SHP-1 to phagocytic cell function, bone marrow neutrophils were isolated from both me/me and me(v)/me(v) mice and examined with respect to their responses to various stimuli. The results of these studies revealed that both quiescent and activated neutrophils from motheaten mice manifested enhanced tyrosine phosphorylation of cellular proteins in the 60- to 80-kDa range relative to that detected in wild-type congenic control neutrophils. MOTHEATEN: neutrophils also demonstrated increased oxidant production, surface expression of CD18, and adhesion to protein-coated plastic. Chemotaxis, however, was severely diminished in the SHP-deficient neutrophils relative to control neutrophils, which was possibly attributable to a combination of defective deadhesion and altered actin assembly. Taken together, these results indicate a significant role for SHP-1 in modulating the tyrosine phosphorylation-dependent signaling pathways that regulate neutrophil microbicidal functions.

Animals↗
PubMed2000

Demography and dog-human relationships of the dog population in Zimbabwean communal lands.

Dogs are Zimbabwe's primary vector for rabies, and the majority live in communal lands (traditional agropastoralist rural areas). In 1994, a household questionnaire survey was conducted to provide baseline data on the demography and dog-human relationships of the dogs in the communal lands. The survey showed that all the dogs were owned, and there was no evidence of a feral population. They were unrestricted and semi-dependent on people. The numbers of dogs per capita varied little in each communal land, resulting in higher dog densities in communal lands with higher human densities, and indicating that people were not intolerant of dogs at higher densities. The population turnover was rapid: the life expectancy of the dogs was 1.1 years, the mean age 2.0 years, and 71.8 per cent died in their first year. The population was heavily skewed towards juveniles, with 40.8 per cent aged less than 12 months. Despite the high juvenile mortality, the population was growing by 6.52 per cent per annum. It was estimated that in 1994 there were 1.36 million dogs in communal lands.

Animals↗
PubMed1999

Phagosomal maturation, acidification, and inhibition of bacterial growth in nonphagocytic cells transfected with FcgammaRIIA receptors.

Phagocytosis and killing of microbial pathogens by professional phagocytes is an essential component of the innate immune response. Recently, heterologous transfection of individual receptors into nonmyeloid cells has been used successfully to elucidate the early steps that signal phagosome formation. It is unclear, however, whether the vacuoles formed by such transfected cells are bona fide phagosomes, capable of fusion with endomembranes, of luminal acidification, and of controlling the growth of microorganisms. The aim of the current study was to determine whether COS-1 and Chinese hamster ovary cells, rendered phagocytic by expression of human FcgammaRIIA receptors, express the cellular machinery required to support phagosomal maturation. Immunolocalization studies demonstrated that early endosomes, as well as late endosomes and/or lysosomes, fuse sequentially with phagosomes in the transfectants. Microfluorescence ratio imaging of particles labeled with pH-sensitive dyes revealed that maturation of the phagosome was accompanied by luminal acidification. The drop in pH, which attained levels comparable to those reported in professional phagocytes, was prevented by inhibitors of vacuolar-type H(+)-ATPases. Optimal phagosomal acidification required elevation of cytosolic [Ca(2+)], suggesting that it results from fusion of endomembranes bearing proton pumps. Moreover, the transfected cells effectively internalized live bacteria. Opsonization was essential for bacterial internalization, implying that it occurred by FcgammaRIIA-mediated phagocytosis, as opposed to invasion. Uptake into phagolysosomes was associated with inhibition of bacterial growth, due at least in part to the low intraphagosomal pH. These studies indicate that the biochemical events that follow receptor-mediated particle internalization in cells transfected with FcgammaRIIA receptors closely resemble the process of phagosomal maturation in neutrophils and macrophages. FcgammaRIIA-transfected cells can, therefore, be used as a model for the study of additional aspects of phagocyte biology.

Animals↗
PubMed1998

Importance of MEK in neutrophil microbicidal responsiveness.

Exposure of neutrophils to inflammatory stimuli such as the chemoattractant FMLP leads to activation of responses including cell motility, the oxidative burst, and secretion of proteolytic enzymes. A signaling cascade involving sequential activation of Raf-1, mitogen-activated protein kinase (MEK), and extracellular signal regulated kinase (ERK) is also rapidly activated after agonist exposure. The temporal relationship between these events suggests that the kinases may be involved in triggering the effector functions, but direct evidence of a causal relationship is lacking. To assess the role of the MEK/ERK pathway in the activation of neutrophil responses, we studied the effects of PD098059, a potent and selective inhibitor of MEK. Preincubation of human neutrophils with 50 microM PD098059 almost completely (>90%) inhibited the FMLP-induced activation of MEK-1 and MEK-2, the isoforms expressed by neutrophils. This dose of PD098059 virtually abrogated chemoattractant-induced tyrosine phosphorylation and activation of ERK-1 and ERK-2, implying that MEKs are the predominant upstream activators of these mitogen-activated protein kinases. Pretreatment of neutrophils with the MEK antagonist inhibited the oxidative burst substantially and phagocytosis only moderately. In addition, PD098059 antagonized the delay of apoptosis induced by exposure to granulocyte-macrophage CSF. However, the effects of PD098059 were selective, as it failed to inhibit other responses, including chemoattractant-induced exocytosis of primary and secondary granules, polymerization of F-actin, chemotaxis, or activation of phospholipase A2. We conclude that MEK and ERK contribute to the activation of the oxidative burst and phagocytosis, and participate in cytokine regulation of apoptosis.

Actins↗
PubMed1998

The short-term financial costs of abnormal Pap smears to women and government in Australia.

Using data collected from a private Canberra colposcopy service, we examined the direct costs, to women and government, of the gynaecological care of women with cervical cytological abnormalities and determine the potential savings of implementing the Commonwealth recommendations for the clinical care of women with screen-detected abnormalities. We performed a case note audit of 502 women who first attended a gynaecologist because of an abnormal Pap smear between 1 January 1989 and 30 April 1990. The smear resulting in their referral--their presenting smear--was categorised as No CIN (showing no evidence of cervical intraepithelial neoplasia), CIN 1, CIN 2 and CIN 3. The average costs to government (p for trend < 0.001) and women (p for trend = 0.006) increase as the presenting smear increases in severity; the median costs to government (p for trend < 0.001) and women (p for trend < 0.001) also rose with increasing cytological severity. Treatment of CIN 1 and No CIN accounted for half the costs incurred by government and women. Although costs increase with increasing severity of cytological abnormality, adherence to new Australian guidelines for the gynaecological care of women with screen-detected cervical abnormalities could result in substantial short-term savings to government and women.

Adult↗
PubMed1998

Volumetric changes following barrier regeneration procedures for the surgical management of grade II molar furcation defects in baboons: II. Bone, cementum, epithelium, and connective tissue.

In Part I, a computer imaging technique was used to measure the volumetric fill that occurred in surgically created grade II molar furcation defects after they had been treated using the principles of guided tissue regeneration. In Part II, the volumetric fill for each of the specific tissues comprising the defect fill (epithelium, connective tissue, bone, and cementum) was compared. The histologic material consisted of defects treated using one of three types of surgical treatment as well as untreated control sites. All volumetric measurements were expressed as a percentage of the original surgically created defect size, with 100% indicating complete healing of the defect. The results indicate that none of the defects achieved complete healing. Teeth receiving flap debridement had the most overall defect fill (79.50% comprised of 17.13% bone, 35.81% connective tissue, 37.35% epithelium, and 9.71% cementum). Teeth that received a biodegradable barrier showed a mean overall defect fill of 74.98% (7.41% bone, 47.13% connective tissue, 36.20% epithelium, and 9.26% cementum. Sites treated with an exclusion barrier showed 70.75% overall fill (9.63% bone, 40.89% connective tissue, 39.00% epithelium, and 10.48% cementum). The untreated control teeth showed a mean overall fill of 78.70% (5.56% bone, 59.11% connective tissue, 31.06% epithelium, and 4.27% cementum). No significant differences were found among teeth within the same animal and between treatment and controls. The following conclusions were drawn: (1) connective tissue comprised nearly one half of the total fill of the surgically created defects; (2) the percentage of new bone growth was significantly lower than anticipated; and (3) no significant differences were found among the treatment modalities and the untreated control sites for each of the specific tissue types.

Animals↗
PubMed1997

Child Health Surveillance in England and Wales: the bad news.

Postal surveys were conducted in 1993 among all, or samples of, six groups of providers and managers of pre-school child health surveillance (CHS) in England and Wales. Content analyses were also carried out of strategic policy statements for CHS produced by 54 district health authorities in England and Wales. The surveys aimed to document the views and experiences of CHS providers and managers about the impact of recent changes affecting the structure and operation of CHS, including the publication of Health for All Children, the 1990 Contract for General Practitioners (GPs), the implementation of the National Health Service and Community Care Act 1990, and the changing roles of community doctors and health visitors. Four adverse findings from the surveys are discussed: fragmentation in the child health service; the unwanted effects of the NHS internal market; the adverse consequences of the changing role of health visitors; and the concerns voiced by the community doctors about the quality of CHS in general practice.

Child↗
PubMed1997

Child Health Surveillance in England and Wales: the good news.

Postal surveys were conducted in 1993 among all, or samples of, six groups of providers and managers of pre-school child health surveillance (CHS) in England and Wales. Content analyses were also carried out of strategic policy statements for CHS produced by 54 district health authorities in England and Wales. The surveys aimed to document the views and experiences of CHS providers and managers about the impact of recent changes affecting the structure and operation of CHS, including the publication of Health for All Children, the 1990 Contract for General Practitioners (GPs), the implementation of the National Health Service and Community Care Act 1990, and the changing roles of community doctors and health visitors. Five positive findings from the surveys are discussed: the impact of the first edition of Health for All Children; improvements in the development and use of child health information systems; the beneficial effects of the growing Involvement of GPs in CHS; the developing understanding of, and commitment to, the principle of clinical audit in CHS; and the growing collaboration between providers in the NHS internal market. A separate paper reports the negative findings from the study.

Child↗
PubMed1997

A cost-effectiveness analysis of directly observed therapy vs self-administered therapy for treatment of tuberculosis.

STUDY OBJECTIVES: To compare the costs and effectiveness of directly observed therapy (DOT) vs self-administered therapy (SAT) for the treatment of active tuberculosis. DESIGN: Decision analysis. SETTING: We used published rates for failure of therapy, relapse, and acquired multidrug resistance during the initial treatment of drug-susceptible tuberculosis cases using DOT or SAT. We estimated costs of tuberculosis treatment at an urban tuberculosis control program, a municipal hospital, and a hospital specializing in treating drug-resistant tuberculosis. OUTCOME MEASURES: The average cost per patient to cure drug-susceptible tuberculosis, including the cost of treating failures of initial treatment. RESULTS: The direct costs of initial therapy with DOT and SAT were similar ($1,206 vs $1,221 per patient, respectively), although DOT was more expensive when patient time costs were included. When the costs of relapse and failure were included in the model, DOT was less expensive than SAT, whether considering outpatient costs only ($1,405 vs $2,314 per patient treated), outpatient plus inpatient costs ($2,785 vs $10,529 per patient treated), or outpatient, inpatient, and patients' time costs ($3,999 vs $12,167 per patient treated). Threshold analysis demonstrated that DOT was less expensive than SAT through a wide range of cost estimates and clinical event rates. CONCLUSION: Despite its greater initial cost, DOT is a more cost-effective strategy than SAT because it achieves a higher cure rate after initial therapy, and thereby decreases treatment costs associated with failure of therapy and acquired drug resistance. This cost-effectiveness analysis supports the widespread implementation of DOT.

Antitubercular Agents↗
PubMed1997

Volumetric changes following barrier regeneration procedures for the surgical management of grade II molar furcation defects in baboons: I. Overall defect fill.

A computer imaging technique has been advocated for measuring the volumetric fill in furcation defects. Histologic material for this investigation was obtained from an animal study using five adult baboons (Papio anubis). The photographed histology was converted into digitized electronic information, and a computer calculated the overall volume of defect fill for the treated and the untreated control sites. All volumetric measurements were expressed as a percentage of the original surgically created defect size, with 100% indicating complete healing of the defect. The results indicate that none of the defects achieved complete healing. Teeth that had received flap debridement had the most overall defect fill (79.50%). Teeth that received a biodegradable barrier (Epi-Guide) showed a mean overall defect fill of 74.98%, while sites treated with an exclusion barrier (Gore-Tex) showed 70.75% overall fill. The untreated control teeth showed a mean overall fill of 78.70%. A variety of statistical tests revealed no significant differences among teeth within the same animal and between treatments and controls. The following conclusions were drawn: (1) digital imaging technology is a useful research tool for determining the volume of defect fill in surgically created grade II molar periodontal furcation defects in the baboon model; and (2) no significant differences were found among the treatment modalities and the untreated control sites.

Animals↗
PubMed1996

Chemotactic peptide-induced activation of MEK-2, the predominant isoform in human neutrophils. Inhibition by wortmannin.

Exposure of neutrophils to a variety of agonists including chemoattractant peptides and cytokines induces degranulation and activation of the oxidative burst which are required for bacterial killing. The signaling pathways regulating these important functions are incompletely characterized. Mitogen-activated protein (MAP) kinases, which include the extracellular signal-regulated kinases (ERKs), are activated rapidly in neutrophils, suggesting that they may regulate cell activation. We found that neutrophils express two isoforms of MAP/ERK kinase (MEK), mixed-function kinases that are responsible for phosphorylation and activation of ERK. Like MEK-1, MEK-2 was found to reside in the cytosol both before and after stimulation. Studies were undertaken to define the relative abundance and functional contribution of MEK-1 and MEK-2 in neutrophils and to characterize the signaling pathways leading to their activation. Although the abundance of the two isoforms was similar, the activity of MEK-2 was at least 3-fold greater than that of MEK-1. A rise in cytosolic [Ca2+] was insufficient for MEK stimulation, and blunting the [Ca2+] change with intracellular chelators failed to prevent receptor-mediated activation of either isoform, implying that cytosolic Ca2+ transients are not necessary. In contrast, both MEK-1 and MEK-2 were activated by exposure of cells to protein kinase C (PKC) agonists. Conversely, PKC antagonists inhibited the chemotactic stimulation of both isoforms, suggesting that PKC was required for their activation. Despite these similarities, clear differences were also found in the pathways leading to activation of the MEK isoforms. In particular, MEK-2 was considerably more sensitive than MEK-1 to the phosphatidylinositol 3-kinase inhibitor wortmannin. Phosphorylation and activation of ERK-1 and ERK-2 were also reduced by this inhibitor. In summary, MEK-2 is stimulated in formyl-methionyl-leucyl-phenylalanine-treated neutrophils, where it appears to be functionally the predominant isoform. The time course and inhibitor sensitivity of MEK-2 activation parallel those of several components of the microbicidal response, suggesting a signaling role of the MEK-ERK pathway.

Amino Acid Sequence↗
PubMed1996

A cost-effectiveness analysis of enalapril maleate in the management of congestive heart failure in Australia.

BACKGROUND: This study is motivated by the results of the SOLVD treatment trial (N Engl J Med 1991; 325: 293-302) which demonstrated the clinical efficacy of enalapril in the treatment of congestive heart failure but did not undertake an economic evaluation of enalapril therapy. AIMS: To undertake a cost-effectiveness analysis of enalapril maleate versus placebo, in conjunction with conventional treatment, in the management of congestive heart failure in Australia. METHODS: The published results from the SOLVD treatment trial are used to estimate the increase in survival, and the reduction in the number of hospitalisations, arising from the use of enalapril in the management of congestive heart failure. The costs of enalapril therapy are estimated using Australian data on the drug and non-drug costs of enalapril therapy and the costs of hospitalisation. RESULTS: Enalapril therapy increases mean survival in heart failure patients by 1.68 to 1.80 months. The average additional drug and non-drug cost of enalapril therapy is estimated to be $1890 over a four year period, against which must be offset cost savings from a reduction in hospitalisations of $2060 to $2140. On balance, therefore, enalapril is cost saving, reducing health care costs for a congestive heart failure patient on average by $170 to $250 over a four year period. This value is sensitive to estimates of cost offsets and of improved survival which can result in either a net cost saving with enalapril of approximately $1200 per patient or a net additional cost of up to $3000 per patient (over four years) or greater than $20,000 per life-year saved. CONCLUSIONS: The addition of enalapril to conventional management of congestive heart failure in Australia should improve survival and may provide a net reduction in treatment costs compared with conventional management alone.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

The measurement of molar furcation defect fill using digital computer technology--report on a new technique.

Recent advances in digital imaging technology have opened up new horizons for dental researchers. This study demonstrates the efficacy of a new technique for measuring regeneration in surgically created molar furcal defects. The investigators evaluated histologic material from a recently completed animal study using five adult baboons. In the animal study, surgically created molar furcation defects were treated using the principles of guided tissue regeneration. From the histologic data of one animal a computer calculated the volume of new bone, connective tissue, epithelium, and cementum as a percentage of the original defect size. The results of this study indicated that digital imaging technology is a useful research tool for determining the volume of defect fill in surgically treated Grade II molar furcation defects in the baboon animal model.

Animals↗
PubMed1995

Estimating treatment cost functions for progressive diseases: a multiproduct approach with an application to breast cancer.

Using the theory of multiproduct cost functions, a treatment cost function is derived for diseases which progress through a number of stages. The output classes are conceived as the stages at detection of the disease, with the unit of output within each class being the treated case. The derivation clarifies the assumptions underlying various specific functional forms for the treatment cost function. An empirical application to the treatment of breast cancer is provided, producing evidence on an important issue in the economics of screening programs, viz. whether detection of breast cancer at an earlier stage results in treatment cost savings.

Aged↗
PubMed1995

The costs of treating breast cancer in Australia and the implications for breast cancer screening.

The aim of the study was to determine if there is a relationship between the stage of breast cancer at the time of detection and the costs of treatment and to assess whether any such relationship would have an influence on the cost of a mammographic screening programme. A retrospective analysis of the stage at presentation for primary breast cancer and the treatment costs over the duration of treatment was made. Multiple regression analysis was employed, with treatment cost as the dependent variable and categorical variables to represent stage at detection. A total of 301 women whose treatment for breast cancer commenced at the Royal Brisbane Hospital participated in the study. A statistically significant relationship was found between the stage of disease at the time of detection and subsequent treatment costs; more advanced stages of disease incurred higher treatment costs. This relationship was robust even after taking into account the age of patients, their discharge status, and differences between patients in the duration of treatment. When the effect of earlier detection on treatment cost was assessed in relation to a breast screening programme, cost savings were estimated to be in the range of 8-36% of total screening costs. There are treatment cost savings to be gained from breast cancer screening as a result of the detection of earlier stages of disease. These treatment cost savings should be offset against the cost of a mammographic screening programme.

Adult↗