Biomedical subjects
Publications and source records attributed to J Bishop.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The usefulness of surveys for measuring the severity of asthma in school-age children depends on the availability of reliable and valid questionnaires. The aim of this study was to develop a measure of functional severity of asthma over the previous 12 mo, for use in population studies and in investigating treatment regimens. Of 10,198 children surveyed, 9,192 (90%) in school Years 2, 7, and 10 (mean ages 8, 13, and 16 yr) in Melbourne were screened for wheeze. The parents of the 1,267 children with wheeze were interviewed. Symptoms and restriction of activity due to asthma were analyzed using factor analysis and the partial credit version of the item response theory measurement model. The result was a continuous severity scale that was highly consistent with the data, and with goodness of fit statistics indicating the severity of 97% of children was well described by the scale. The scale correlated significantly with school absence due to wheeze (r = 0.35), functional impairment during the 2 wk before interview (Functional Status II-R [FSII-R], r = 0.30), visits to medical care for wheeze (r = 0.22), and amount of medication (r = 0.36). For descriptive purposes, a simple index with four bands of severity was developed from the continuous severity scale: low severity (47% of children with wheeze), moderate (30%), mild (18%), and high (5%). The scale and index facilitate standardized description of the impact of asthma on daily life on the basis of responses to six survey questions.
Comparison of asthma prevalence between populations is difficult because of lack of uniformity of methodology and agreement on the definition. This study aims to determine and compare the prevalence of wheeze and respiratory symptoms in Hong Kong schoolchildren with that in Melbourne children by using identical questionnaires. Schools were randomly selected in different regions of Hong Kong and three age groups (7, 12 and 15 yrs) were chosen for the study. The Chinese version of the questionnaire used in a recent Melbourne survey was distributed to children for completion by their parents. A total of 1,800 questionnaires was issued and 1,689 returned (response rate = 94%). The prevalence of wheeze in the past 12 months was 7 (5.1-8.0), 5 (3.0-6.7) and 4 (1.7-5.6) % for 7, 12 and 15 year olds, respectively. The prevalence of a history of asthma in the respective age groups was 10 (7.1-12.9), 8 (7.5-9.2) and 7 (5.0-9.6) %, respectively. Whilst a history of wheeze ever was more common in boys than in girls and 12 yr olds (14% vs 5%), wheeze in the past 12 months was more common in boys than in girls aged 7 yrs (9 vs 4%). We conclude that the prevalence of wheeze and asthma in school children was low in Hong Kong compared to Melbourne. Environmental differences between the two regions may be important in the pathogenesis.
Several lines of circumstantial evidence support the assumption that protein kinase C (PKC) activation together with elevated levels of cytosolic Ca++ are necessary for T-cell activation and proliferation in response to a physiological stimulus, i.e., MHC class II restricted antigen presentation. By using a potent, cell-permeable and selective inhibitor of PKC, Ro 32-0432, we have tested this hypothesis. Ro 32-0432 inhibits interleukin-2 (IL-2) secretion, IL-2 receptor expression in, and proliferation of, peripheral human T-cells stimulated with phorbol ester together with phytohemagglutin or anti-CD3, but does not inhibit IL-2 induced proliferation in cells already stimulated to express IL-2 receptors. Proliferation of the influenza peptide antigen HA 307-319-specific human T-cell clone (HA27) after exposure to antigen-pulsed autologous presenting cells was also inhibited by Ro 32-0432. Oral administration of Ro 32-0432 inhibited subsequent phorbol ester-induced edema in rats demonstrating the systemic efficacy of the compound to inhibit PKC-driven responses. Induction of more physiologically T-cell driven responses such as host vs. graft responses and the secondary paw swelling in adjuvant-induced arthritis were also inhibited by Ro 32-0432. These data demonstrate the crucial role for PKC in T-cell activation and that selective p.o. bioavailable PKC inhibitors are efficacious in preventing T-cell driven chronic inflammatory responses in vivo. Inhibition of PKC represents an important mechanistic approach to prevent T-cell activation and compounds of this class may have important therapeutic applicability to chronic inflammatory and autoimmune diseases.
An increasing number of biochemical tests for the detection of ailments such as hepatitis, AIDS, listeria poisoning etc are becoming qualitative in nature since the concern is over whether contamination is present or not rather than to what degree it is present. Many tests have an underlying quantitative scale that is dichotomised by the calculation of a detection limit, whereby a result is deemed negative, say, if its assay response is less than the detection limit and positive otherwise. A number of methods have been proposed for determining the detection limit and a few authors have tried to compare some of these methods. To date, as far as we are aware, these comparisons have been neither exhaustive nor conclusive. We propose a comparison criterion based on the false positive and false negative rates and use this criterion to assess five different methods via a simulation study. For the simulation model used, under the conditions imposed, we conclude that a detection limit based on control samples is probably the most efficient. Each method of calculating the detection limit has a coefficient associated with it for determining the exact position of the detection limit. The criteria, to date, for selecting the value of this coefficient seem arbitrary since whole numbers are often quoted, presumably reflecting convenience. Our simulation approach provides a possible method for determining the value of the coefficient which gives rise to a specified false positive or false negative rate.
BACKGROUND: Paclitaxel (Taxol) is the first of a new class of cytotoxic agents with activity against tumors resistant to other drugs. For clinical use, paclitaxel is currently formulated in a vehicle of 50% ethanol and 50% polyethoxylated surfactant Cremophor EL (Cremophor). We have previously shown that Cremophor will block the P-glycoprotein drug efflux pump responsible for the multidrug-resistant phenotype. Overexpression of P-glycoprotein is one mechanism of in vitro resistance to a number of currently used cytotoxic agents including paclitaxel. PURPOSE: Our aim was to develop a bioassay to measure plasma levels of Cremophor and to determine whether or not plasma levels of Cremophor achieved during paclitaxel therapy are sufficient to inhibit the activity of the P-glycoprotein. METHODS: All patients studied had histologically proven, advanced ovarian carcinoma with measurable or evaluable disease and had received at least one prior platinum-containing regimen. The bioassay used flow cytometry to measure the increase in equilibrium intracellular daunorubicin levels in multidrug-resistant human T-cell leukemia cells (CEM/VLB100) in the presence of a series of concentrations of Cremophor. Levels of Cremophor were measured in plasma from 21 patients after a 3-hour infusion of 135 or 175 mg/m2 paclitaxel. Both dose levels were given following premedication with oral dexamethasone, intravenous promethazine hydrochloride, and intravenous cimetidine. The Cremophor bioassay involved incubation of CEM/VLB100 cells (5 x 10(5)) for 1 hour with 2 micrograms/mL daunorubicin in 0.5 mL HL-1 medium plus 0.5 mL plasma prior to flow cytometric analysis. Pretreatment plasma was used to derive a standard curve for the effect of Cremophor on equilibrium daunorubicin levels. All measurements were done in triplicate. RESULTS: In vitro experiments indicated that, for maximal inhibition of P-glycoprotein activity, concentrations of Cremophor of 0.1% (vol/vol) were required. At the end of a 3-hour infusion of paclitaxel, plasma levels of Cremophor in 19 of 21 patients were 0.1% or higher and 0.09% in the remaining two. Concentrations of 5-20 microM paclitaxel dissolved in ethanol without Cremophor did not inhibit P-glycoprotein in this assay. CONCLUSION: The concentrations of Cremophor measured in plasma drawn from patients after a 3-hour infusion of paclitaxel at 135 or 175 mg/m2 were found to be sufficient to inhibit P-glycoprotein activity in vitro. IMPLICATIONS: The efficacy of paclitaxel against some tumors may be aided by its administration in a vehicle solution containing Cremophor in quantities that reach concentrations in the plasma sufficient to reverse multidrug resistance of neoplastic cells.
The aim of the study was to determine if the prevalence of symptoms suggestive of asthma in school-age children was similar in three countries with differing language and culture. To answer this question, we used the same instrument, translated appropriately, for schoolchildren in Melbourne, Australia, St. Gallen, Switzerland, and La Serena, Chile. A three page respiratory symptoms questionnaire was issued to schools for distribution to children for completion by parents and return to the school. Three age groups were selected for study, based on the average age of the school grade. Grades were used with average ages of 7, 12, and 15 years, respectively. A total of 26,628 questionnaires were issued to parents (Australia, 10,981; Switzerland, 4,464; Chile, 11,183). The response rates for each country were 89% for Australia, 97.5% for Switzerland, and 71% for Chile. The prevalence of wheezing in the last 12 months for 7 year olds was 23.1% in Melbourne, 7.4% in St. Gallen, and 26.5% in La Serena; for 12 year olds it was 20.9% in Melbourne, 6.0% in St. Gallen, and 21.1% in La Serena; for 15 year olds it was 18.6% in Melbourne, 4.5% in St. Gallen, and 17.7% in La Serene. A history of wheezing was more common in boys than girls at age 7 in Melbourne and St. Gallen, but not La Serena. This difference was less at age 12 and was not seen at age 15. Among those who had reported wheezing in the last 12 months, bronchodilator use was reported by 83% (1,611/1,948) from Melbourne, 46% (118/259) from St. Gallen, and 47% (538/1,140) from La Serena.(ABSTRACT TRUNCATED AT 250 WORDS)
Since the introduction of Cohen's kappa as a chance-adjusted measure of agreement between two observers, several "paradoxes" in its interpretation have been pointed out. The difficulties occur because kappa not only measures agreement but is also affected in complex ways by the presence of bias between observers and by the distributions of data across the categories that are used ("prevalence"). In this paper, new indices that provide independent measures of bias and prevalence, as well as of observed agreement, are defined and a simple formula is derived that expresses kappa in terms of these three indices. When comparisons are made between agreement studies it can be misleading to report kappa values alone, and it is recommended that researchers also include quantitative indicators of bias and prevalence.
Methods of quantifying cartilage destruction are described using a sponge/cartilage implant model in the rat. A cylinder of bovine nasal cartilage was positioned in the center of a sponge which had been pretreated with an irritant. The sponge/cartilages were then implanted subcutaneously into the backs of rats for periods of up to 16 days. The implanted sponges were rapidly surrounded by granulation tissue, maximal on day 2, and infiltrated by inflammatory cells which reached peak levels on day 9. Analysis of the cartilage shows an initial increase in wet weight and rapid loss of glycosaminoglycans. These changes were later followed by loss of cartilage wet weight and significant loss of hydroxyproline content. In a separate study, the effects of Mycobacterium tuberculosis (Mtb), kaolin, and zymosan were compared (1 mg/sponge) and the results showed that only Mtb induced pronounced inflammation and degradation of cartilage. The cartilage degradation directly correlated with the granulation tissue weight, but not with cellular infiltration. We believe that this simple, reproducible in vivo model could be used to elucidate the mechanisms involved in the destructive process and evaluate the efficacy of inhibitors of cartilage degradation.
The aim of the study was to investigate the relationship between myocardial collagen and regional echo amplitude in humans with non-fibrotic myocardium. The ratio of myocardial collagen to total myocardial protein was determined as the hydroxyproline/leucine ratio in endomyocardial biopsies obtained from the right ventricular side of the interventricular septum in orthotopically transplanted hearts. Regional echo amplitude was measured in the interventricular septum. Patients were studied prospectively. Twenty-five patients (five female, 20 male) who had undergone orthotopic cardiac transplantation were studied 355 to 2939 days (1009 +/- 718, mean +/- SD) post-transplantation at the time of annual cardiac catheterization and endomyocardial biopsy. Patient ages varied from 22 to 62 years (46 +/- 11). Donor ages were 14 to 47 years (25 +/- 8) and the ischaemic time, 90 to 245 min (151 +/- 42). Cardiac transplantation was performed for end-stage cardiac failure in all patients. The aetiology of cardiac failure was valvular heart disease in three, dilated cardiomyopathy in eight and ischaemic heart disease in the remainder. Echo amplitude studies were performed within 24 h of endomyocardial biopsy. All but one patient were on an immunosuppressive regime consisting of cyclosporine A and azathioprine with additional steroids in three. The remaining patient, who was the longest surviving patient in the study group, had never been treated with cyclosporine. This patient was maintained on steroids and azathioprine alone. No patient had clinical or histological evidence for acute cardiac rejection and all were clinically well. Five patients had angiographic evidence of coronary artery disease. All subject studies were performed at Harefield Hospital.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
The ability of diagnosis related groups (DRG) and refinement diagnosis related groups (RDRG) to measure differences in case-mix was investigated using discharge data for patients < 18 years of age from three specialist children's hospitals and four district hospitals. While the three children's hospitals each had a greater percentage of RDRG for more complex patients, only one children's hospital had more complex patients based on DRG and RDRG cost weights and on the percentage of diagnoses per discharge. Cost weights based on USA practices may be inappropriate in Australia, and Australian weights will be necessary for firm conclusions. Refinement diagnosis related groups with appropriate cost weights may be acceptable measures of case-mix in specialist children's hospitals, but they have inherent limitations for paediatric patients in that many complex paediatric patients are ill very seriously with one disorder, whereas complex adult patients usually have secondary diagnoses and secondary procedures. Moreover, no DRG version developed in the US will be suitable for use in Australia unless it takes account of medical costs and transfer practice.
OBJECTIVE: To investigate the effect of subcutaneous oestradiol and testosterone on the proportion of type III collagen in the skin of postmenopausal women. DESIGN: A cross sectional comparison. SETTING: Dulwich Hospital menopause clinic. SUBJECTS: Fourteen untreated women and 11 women who had received subcutaneous oestradiol and testosterone for a median 8.0 years (range 3-14). Ten of the untreated women received subcutaneous hormone implants and the effect on skin collagen was studied prospectively. MEASUREMENTS: The proportion of type III collagen in skin biopsies taken from the lateral aspect of the thigh. RESULTS: The median type III collagen content in the skin of the women who had received hormone replacement therapy (25.4%, range 21.4-30.2) was significantly higher (P < 0.01) than in the untreated women (19.6%, range 18.2-28.8). The proportion of type III collagen in the skin of 10 untreated women increased significantly (P < 0.01) from a median of 19.9% (range 18.2-23.9) to 22.4% (range 20.5-31.5) following 6 months of treatment with hormone implants. CONCLUSION: This study indicates an increase in the proportion of type III collagen in women receiving hormone replacement therapy.
OBJECTIVE: To determine whether the separation rate from the hospital for children aged 0-15 years in Victoria was higher for those resident in the country area of the State in comparison with the metropolitan area and, if it was, to investigate possible explanations. DESIGN: Discharge data from all public hospitals in Victoria for children aged 0-15 years for the financial years 1988-89, 1989-90 and 1990-91 were analysed with detailed analysis being done on the 1990-91 data set. Discharge rates were determined according to the local authority area of residence. Patients were grouped according to Diagnosis Related Groups (DRGs) version 5. RESULTS: Children living in the country area showed a separation rate of 50 per cent greater than that for the metropolitan area. Separation rates for local authority areas were remarkably constant over the three years. Country local authority areas with the highest separation rates had separation rates for asthma and bronchitis (DRG 98), almost four times that of metropolitan residents, and for otitis media and upper respiratory infection (URI), a rate almost ten times that of metropolitan residents. CONCLUSION: It is suggested that variation in medical practice was the most likely explanation for the observed differences.
Numerous papers have been written to show which combinations of Shewhart-type quality-control charts are optimal for detecting systematic shifts in the mean response of a process, increases in the random error of a process, and linear drift effects in the mean response across the assay batch. One paper by Westgard et al. (Clin Chem 1977;23:1857-67) especially seems to have attracted the attention of users. Here we derive detailed results that enable the characteristics of the various Shewhart-type control schemes, including the multirule scheme (Clin Chem 1981;27:493-501), to be calculated and show that a fundamental formula proposed by Westgard et al. in the earlier paper is in error, although their derived results are not seriously wrong. We also show that, from a practical point of view, a suitably chosen Cusum scheme is near optimal for all the types and combinations of errors discussed, thereby removing the selection problem for the user.
OBJECTIVE: To determine whether the high prevalence of reported asthma in Melbourne schoolchildren is seen in rural Victoria. DESIGN: A questionnaire on respiratory symptoms was distributed to children to be completed by parents and returned to the school. Results were compared with a previous Melbourne study. SETTING: Two hundred and twenty-seven government and non-government primary schools in five rural regions of Victoria: coast, wheatbelt, riverland, highland and Latrobe valley. SUBJECTS: All children enrolled in grade 2 were invited to join the study. Parents completed questionnaires for 4661 children after 4886 questionnaires were distributed (response rate, 95%). MAIN OUTCOME MEASURE: History of wheeze in the past 12 months. RESULTS: The overall prevalence of wheeze in the last 12 months was 23.6%. There was a significant difference overall in this rate across the five rural areas and Melbourne, with the Latrobe Valley (26.2%) and highland areas (25.0%) having the highest rate, and the wheatbelt the lowest (19.6%). The spectrum of severity of asthma was similarly distributed across rural regions, although severe episodes were significantly more frequently reported by parents from rural areas than by parents in Melbourne. The reported use of bronchodilators and diagnosis of asthma showed a similar pattern of variation to that of the 12-month prevalence of wheeze. CONCLUSION: The prevalence of asthma in 7-year-old children is similar for rural Victoria as a whole compared with Melbourne, but there is variability in asthma prevalence in individual rural areas which is difficult to account for in terms of known environmental precipitants.