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Biomedical subjects

J Bishop

Publications and source records attributed to J Bishop.

At least 19 recordsLinked to original sources
PubMed1992

Prevalence of asthma in regional Victorian schoolchildren.

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.

Asthma↗
PubMed1992

Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer.

Toremifene is an antiestrogen that binds strongly to estrogen receptors (ER). A total of 19 previously treated postmenopausal women with metastatic breast cancer whose performance status was good and whose ER status was positive or unknown were studied to determine the maximum tolerated dose of toremifene. Cohorts of patients received 200, 300, or 400 mg/m2 p.o. daily until relapse or unacceptable toxicity had occurred. Nausea, vomiting, and dizziness were dose-related. Three of five patients receiving 400 mg/m2 experienced moderate or severe vomiting and another developed reversible disorientation and hallucinations. Mild sweating, peripheral edema, vaginal discharge, and hot flushes were encountered at all doses. Reversible corneal pigmentation was identified in seven cases but was not of clinical importance. The pharmacokinetics of toremifene was studied weekly and in detail on day 42 using a high-performance liquid chromatographic (HPLC) assay that identified the parent compound and three active metabolites, N-desmethyltoremifene, (deaminohydroxy)toremifene, and didemethyltoremifene. Steady state was achieved at 1-3 weeks. The toremifene area under the curve and the maximal concentration were dose-dependent at high doses. The recommended phase II dose is 300 mg/m2 p.o. daily.

Adult↗
PubMed1992

Evaluation of the properties and reliability of a clinical severity scale for acute asthma in children.

The inter-observer agreement (reliability) and validity of a clinical asthma severity scale (ASS) derived from separate scores of wheeze, heart rate and accessory muscle use (each on a 4-point scale) were studied in 60 children aged between 6 months and 17 years (mean 5.4 years). Independent assessments of these clinical parameters were made by two paediatricians, and they also rated patients as having a mild, moderate, severe or very severe acute episode (clinical judgement rating, CJR). Oxygen saturation (SaO2) was measured concurrently by a Biox 3700 pulse oximeter and readings were categorized as mild (SaO2 greater than or equal to 94%), moderate (91-93%) and severe (less than 91%). Agreement between clinicians was assessed by the weighted kappa statistic (kappa W). Agreement for the ASS score compared to the severity grade obtained from SaO2 was slight (kappa W = 0.34) and compared to CJR the kappa W was 0.55. An ASS score of moderate or worse (greater than 3) had sensitivity of 97% and specificity of 50% for prediction of admission. The maximum frequency and duration of nebulizer therapy following admission were significantly greater for severe patients than for moderate patients. Length of hospital stay did not reflect the ASS score in the emergency department but total duration of functional disability increased with ASS score. The substitution of an adjusted heart rate score for the raw heart rate score used in ASS detracted from scale performance. The ASS is an imprecise but reasonable quantitative measure of the severity of an acute episode of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The severe combined immunodeficient (SCID) mouse as a model for human myeloid leukemias.

Recent work has demonstrated the ability of lymphoblastic leukemias of pre-B- and T-cell origin to grow in severe combined immunodeficient (SCID) mice with a pattern reminiscent of the human clinical disease. Here, we investigated the possibility of engrafting human myeloid leukemias using both established cell lines and primary patient material. Whereas the two growth factor-independent cell lines K562 and U937 grew aggressively and induced leukemia in these animals, three other myeloid cell lines which require interleukin 3 or granulocyte-macrophage colony-stimulating factor for continuous growth in vitro failed to induce disease. Primary bone marrow and peripheral blood cells from five out of seven patients with different types of myeloid leukemias (undifferentiated, megakaryoblastic, monoblastic and chronic myelogenous leukemia in blast crisis) induced patterns of leukemic infiltration that were distinct for each leukemia subtype. The diagnosis of leukemia in SCID mice was established by microscopic detection of myeloblasts in the bone marrow, peripheral blood and, in some instances, in extramedullary sites, including the central nervous system and gonads. The karyotype and phenotype of the blasts recovered from mouse tissues were identical to those of the original patient cells. Moreover, human specific ALU sequences were amplified from the bone marrow DNA by polymerase chain reaction. Despite their ability to grow in vivo by serial transfers in SCID mice, the leukemic cells recovered from mouse tissues could not be maintained in vitro, even in the presence of recombinant cytokines. Overall, these data indicate that the SCID mouse may represent a useful animal model for human myeloid leukemias and for the development of new pharmacological and molecular approaches to therapy.

Adult↗
PubMed1991

Prevalence of asthma in Melbourne schoolchildren: changes over 26 years.

OBJECTIVES: To determine the prevalence of asthma in the past 12 months in Melbourne schoolchildren aged 7, 12, and 15 years and to compare the prevalence of a history of asthma with that of 26 years ago. DESIGN: A questionnaire on respiratory symptoms was distributed to children for completion by parents and return to the school. Subjects were selected by a stratified cluster design. SETTING: Government and non-government schools in the greater Melbourne area, Australia. SUBJECTS: 10,981 children. Parents completed questionnaires for 3324 children aged 7, 2899 aged 12, and 2968 aged 15. The overall response rate was 90%. MAIN OUTCOME MEASURES: History of wheeze or asthma in the past 12 months and in lifetime. RESULTS: The prevalences of wheeze in the past 12 months were 23.1%, 21.7%, and 18.6% for 7, 12, and 15 year olds respectively. A history of wheeze was more common in boys than in girls at age 7 (443/1711 v 324/1614) and 12 (418/1767 v 322/1718) but not at age 15. Overall, 78% (1548) of those reporting wheeze also reported a history of asthma and 83% (1611) had used a bronchodilator. The prevalence of a history of asthma among 7 year olds was 46% compared with 19.1% in the 1964 survey, an increase of 141%. CONCLUSIONS: The current prevalence of asthma in Melbourne schoolchildren is high and has risen substantially over the past 26 years.

Adolescent↗
PubMed1991

Limited small cell lung cancer: the effect of radiotherapy on local control following response to chemotherapy.

The survival and rate of chest infield relapse was examined in 48 patients with limited disease small cell lung cancer (LSCLC) who had achieved complete (CR) or partial response (PR) following three courses of chemotherapy. During 1985-1986 chemotherapy consisted of carboplatin and etoposide and during 1986-1987, of etoposide, carboplatin, cyclophosphamide, and vincristine (ECCO). After three courses of chemotherapy, chest irradiation (50 Gy in 25 fractions over 5 weeks) was given to encompass the original tumor volume. Complete responders were also given prophylactic cranial irradiation, 30 Gy in 10 fractions over 2 weeks. Overall median survival of all patients receiving chest irradiation was 17 months from commencement of radiotherapy. The infield relapse-free survival at 24 months was 49% (95% confidence interval: 32-66%). Patients who had only achieved a PR at the time of irradiation were more likely to relapse in the chest than complete responders (p = 0.09). We conclude that local relapse remains a major cause of failure in patients with LSCLC in spite of sequential high dose radiotherapy given to patients who have responded to chemotherapy.

Adult↗
PubMed1991

Concurrent radiotherapy and carboplatin in non small-cell lung cancer: a pilot study using conventional and accelerated fractionation.

Thirteen patients with unresectable non small cell lung cancer were treated with radical radiotherapy and carboplatin administered concurrently. The first 6 patients were treated to a total dose of 60 Gy in 30 fractions in 6 weeks, with carboplatin 70 mg/m2/day on days 1 to 5 during weeks 1 and 5 of radiotherapy. The remaining 7 patients were given 60 Gy in 30 fractions in 3 weeks, treating twice a day (accelerated fractionation). Carboplatin was given as above but only during week 1 of radiotherapy. Twelve patients completed radiotherapy without interruption but 2 patients developed WHO grade 3 neutropenia. Major toxicity was oesophagitis, one patient requiring nasogastric feeding. Average duration of dysphagia (any grade) in the accelerated fractionation group was 21 weeks. Four patients achieved good partial responses even though initial tumour volume was large. We conclude that this treatment is associated with increased but acceptable early mucosal toxicity.

Aged↗
PubMed1991

Pulse oximetry in acute asthma.

The predictive value of pulse oximetry was evaluated in 100 patients who attended the emergency department with acute asthma. Oximetry after treatment with a cut off point of less than 91% had a sensitivity of 42% and specificity of 78% for unfavourable outcome, and oximetry before treatment had a sensitivity of 36% and a specificity of 57%. Despite its low sensitivity, oximetry after treatment does seem to have a role in minimising diagnostic errors in the emergency department, but only when used in conjunction with clinical assessment.

Acute Disease↗
PubMed1991

Novel, potent and selective inhibitors of protein kinase C show oral anti-inflammatory activity.

Clarification of the precise role of protein kinase C (PKC) in cellular functional responses has been hampered by a lack of potent, selective inhibitors. The structural lead provided by staurosporine, a potent but non-selective protein kinase (PK) inhibitor, was used to derive a series of bis(indolyl)maleimides of which the most potent, Ro 31-8425 (I50: PKC = 8 nM) showed 350-fold selectivity for PKC over cAMP-dependent protein kinase. Ro 31-8425 antagonised cellular processes triggered by phorbol esters (potent, specific PKC activators) and inhibited the allogeneic mixed lymphocyte reaction, suggesting a role for PKC in T-cell activation. Methylation of the primary amine in Ro 31-8425 produced an analogue. Ro 31-8830 which, when administered orally, produced a dose-dependent inhibition of a phorbol ester-induced paw oedema in mice (minimum effective dose = 15 mg/kg). Ro 31-8830 also selectively inhibited the secondary inflammation in a developing adjuvant arthritis model in the rat. The results presented here suggest that these selective inhibitors of PKC may have therapeutic value in the treatment of T-cell-mediated autoimmune diseases.

Administration, Oral↗
PubMed1990

The polymerase chain reaction in the diagnosis of vertically transmitted HIV infection.

The presence of HIV-1 DNA sequences in DNA from peripheral blood mononuclear cells (PBMCs) was investigated in a two-stage polymerase chain reaction ('double' PCR) using four sets of nested primers. The PBMCs tested were obtained from 46 children born to HIV-seropositive mothers, seven 'control' children born to HIV-seronegative mothers and seropositive fathers, and 45 healthy adult blood donors who were HIV seronegative. Nine of the children had symptomatic HIV infection and other laboratory features characteristic of HIV infection: all nine were PCR-positive with each set of primers in each of their 22 blood samples tested. The remaining 44 children had no clinical or laboratory evidence of HIV infection, and each of their 50 samples was PCR-negative with each set of primers, as were all blood donor samples. PCR-positive samples were tested in more detail using two of the sets of primers, which spanned hypervariable regions in the env gene. Polyacrylamide gel electrophoresis of DNA amplified from these regions yielded patterns of amplified DNA length variation which were characteristic for each child, and which changed little with time (in serial samples obtained over periods of 3-7 months). This excluded contamination as a cause of PCR positivity. This is the first report of the use of a double PCR for the diagnosis of HIV infection. The results demonstrate the specificity of this PCR method in diagnosis, with failure to reveal in this cohort any cases of vertically transmitted HIV-1 infection in addition to those already confirmed by conventional laboratory techniques.

Child, Preschool↗
PubMed1990

Phase II trial of carboplatin in the management of malignant mesothelioma.

Thirty-one patients with advanced malignant mesothelioma, previously untreated or having received only one prior cytotoxic regimen, were treated in a prospective, single-arm phase II trial with carboplatin (NSC 241240) at a dose of 150 mg/m2 per day intravenously (IV) for 3 days (450 mg/m2/course). One complete remission and four partial remissions were achieved, yielding an overall objective response rate of 16% (95% confidence interval [CI], 5.4% to 34%). The median duration of remission was 8 months (range, 5 to 17). Nonhematological toxicity was mild (only 12% with World Health Organization [WHO] grade 3 vomiting); 16% suffered WHO grade 3 to 4 hematological toxicity, but there were no life-threatening episodes and no treatment-related deaths. Carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in the management of this disease.

Adolescent↗
PubMed1989

Automated quantification of rat plasma acute phase reactants in experimental inflammation.

Methods are described for the quantification of certain acute phase reactants (albumin, iron, fibrinogen, seromucoid, haptoglobin, and ceruloplasmin) in small amounts of plasma using the COBAS-BIO centrifugal analyzer. These methods have been applied to determine the concentrations of these acute-phase reactants (APRs) in rat plasma during the first 5 days of adjuvant-induced arthritis. The levels of the APRs alter with the degree of inflammation in a dose-related manner. Administration of the antiinflammatory and antirheumatic drugs (indomethacin, dexamethasone, and clobuzarit [CLOZIC]) during the course of the adjuvant-induced arthritis reduced the inflammatory response as judged by the measurement of oedema. These compounds, however, show differential effects on the profile of APRs as systemic measurements of the inflammatory disease. The present study shows that specific classes of drug have defined effects on acute-phase protein concentration. We believe that the multiple analysis of APR levels during the course of inflammation may help to distinguish between and elucidate the mechanisms of action, of antiinflammatory and antirheumatic drugs.

Acute-Phase Proteins↗
PubMed1989

Dose intensity and outcome with combination chemotherapy for germ cell carcinoma. Australasian Germ Cell Trial Group.

Two hundred and fifty-three patients with advanced stage germ cell carcinoma received induction chemotherapy with vinblastine, bleomycin and cisplatin, sometimes with subsequent surgical resection of residual masses. Overall, 191 patients (76%) achieved complete remission or no evidence of disease after surgery (CR + NED). With 64 months median follow-up only 24 patients have relapsed (13%) and 68% of all patients treated are long-term survivors and 84% of patients entering CR + NED are alive. Toxicity with this chemotherapy was considerable, including seven deaths from leukopenia and septicaemia and eight deaths from bleomycin lung toxicity. Dose reductions or omissions of the drug from the treatment programme was necessary with cisplatin in 8% of patients, with vinblastine in 37% and with bleomycin in 35% of patients. Analysis of these alterations in dose intensity for each drug revealed that initial treatment response and subsequent survival were not compromised by reductions in intended doses of drug administered for either vinblastine or bleomycin. Too few patients had dose reductions of cisplatin for meaningful analysis. This apparent lack of major dose-response effect for either vinblastine or bleomycin in the present treatment programme for germ cell carcinoma has prompted the initiation of a randomized study to determine whether deletion of bleomycin from treatment for patients with good prognostic pretreatment characteristics improves the therapeutic index of this very successful therapy.

Antineoplastic Combined Chemotherapy Protocols↗