Management of a Jehovah's witness with thrombotic thrombocytopaenic purpura/haemolytic uraemic syndrome.
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Aged↗
Biomedical subjects
T Callaghan
Publications and source records attributed to T Callaghan.
Projecting mammographic screens.
OBJECTIVE: The purpose of mammographic screening is to reduce mortality from breast cancer. This study describes a method for projecting the number of screens to be performed by a mammographic screening programme, and applies this method in the context of New South Wales, Australia. METHOD: The total number of mammographic screens was projected as the sum of initial screens and re-screens, and is based on projections of the population, rates of new recruitment, rates of attrition within the programme, and the mix of screening intervals. The baseline scenario involved: 70% participation of women aged 50-69 years, 90% return rate for the second and subsequent re-screens, 5% annual screens (95% biennial screens), and a specified population projection. The results were assessed with respect to variations in these assumptions. RESULTS: The projections were strongly influenced by: the rate of screening of the target age group; the proportion of women re-screened annually; and the rates of attrition within the programme. Although demographic change had a notable effect, there was little difference between different population projections. Standard assumptions about attrition within the programme suggest that the current target participation rates in NSW may not be achieved in the long term. CONCLUSIONS: A practical model for projecting mammographic screens for populations is described which is capable of forecasting the number of screens under different scenarios. IMPLICATIONS: Projections of mammographic screens provide important information for the planning and financing of equipment and personnel, and for testing the effects of variations in important operational parameters. Re-screening attrition is an important contributor to screening viability.
Adult↗
Comparison of in vivo red cell survival of donations collected by Haemonetics MCS versus conventional collection.
The Haemonetics Multicomponents System (MCS) cell separator allows concurrent donation of red cells in addition to platelets and/or plasma, thus increasing the versatility of apheresis donations. In vivo survival of autologous red cells obtained by MCS was compared with red cells collected conventionally. In this cross-over controlled study, five male volunteers donated one unit of red cells by MCS and one unit of whole blood by the conventional manual method, 3 months apart. After storing donations in SAG-M for 35 days under standard conditions, radioactive (51Cr)-labelled autologous red cells were injected into each donor. The post-transfusion recovery (PTR) of red cells at 24 and 48 h did not show any significant difference between red cells obtained manually and by MCS, indicating that processing differences have no detrimental effects on red cell survival.
Blood Donors↗
Dynamic balanced randomization for clinical trials.
Common methods of treatment allocation for multi-centre and/or stratified randomized clinical trials can result in substantial differences between the number of patients allocated to each treatment arm. This can occur in the overall trial for a permuted block design or within individual institutions/strata when using a minimization scheme. This may lead to a bias in the result. Also, these procedures can be predictable, with the possibility of an investigator-introduced selection bias. An easily implemented method of randomization is proposed which attempts to overcome these problems by balancing treatment allocations both within strata and across the trial as a whole. The method keeps a running tally on total treatment allocation numbers at all stratification levels. When a patient accrues a hierarchical decision rule is applied, and the allocation is deterministic if certain pre-defined limits are exceeded, and random otherwise. The method is an extension of the big stick design of Soares and Wu, and is related to both Zelen's key number randomization methods and the schemes of Nordle and Brantmark. Simulation studies are used to demonstrate that major imbalances possible with other schemes do not occur using this method, and that the potential for selection bias is much reduced.
Algorithms↗
A complete description of the EGF-receptor exon structure: implication in oncogenic activation and domain evolution.
In this paper, we report that the chicken Epidermal Growth Factor Receptor (EGF-R), encoded by the proto-oncogene c-erbB, is comprised of 28 exons and spans over 75 Kb. The four previously identified domains which make up the extracellular ligand binding region of the receptor are coded for by two copies of a 300 amino acid repeat. We have demonstrated that the 3' end of each repeat coincides with the 3' end of the last exon making up the repeat. This alignment suggests that an exon-duplication may have occurred in the ligand-binding region of the gene. The transmembrane domain is encoded within a single exon and the exon boundaries of the catalytic domain closely match those defined by structural homology with other kinases. Along with the 54 chicken splice sites, the region 5' to the first exon was also sequenced. The proposed promoter region is greater than 70% GC, contains five repeats of the consensus Sp1 binding sequence and does not have a CCATT or TATA box. In addition to the presence of these characteristic housekeeping features, expression analysis confirms the promoter activity of this region and four sets of TCC repeats similar to those found in the human EGF-R promoter have been identified. To our knowledge this represents the first complete description of the exon-intron structure of the EGF-receptor family. The elucidation of the EGF-R exon structure provides insight into the domain evolution of the receptor-kinases and the mechanisms for the oncogenic conversion of EGF-R in erythroleukemias and glioblastomas.
Amino Acid Sequence↗
Continuous intravenous infusion of high dose recombinant interleukin 2 for advanced lymphomas--a phase II study.
The prognosis of patients with advanced refractory lymphoma remains poor. We have carried out a Phase II study of continuous high dose intravenous recombinant interleukin 2 alone without LAK cells in this group of patients. Eight patients have so far been treated, 4 with non-Hodgkins lymphoma and 4 with Hodgkins disease. Of the 7 evaluable patients, the maximum response observed was stable disease in 2 patients (1 with NHL and 1 with HD). The other patients' diseases progressed in the face of immune activation following the rIL-2 infusion. Adverse reactions were common but no life-threatening occurred. These results are disappointing. Whether or not lymphokine-activated killer (LAK) cells are needed to improve response rate deserve further investigations.
Adult↗
Thyroid disorders in 2 cases of acute myeloid leukaemia following treatment with recombinant interleukin-2 infusion.
Two AML patients treated with recombinant interleukin-2 infusion without LAK cells developed thyroid complications within 2 months following the treatment. One patient was clinically and biochemically hypothyroid but was negative for thyroid autoantibodies while the other patient developed thyroid microsomal autoantibody but remained euthyroid. These 2 cases represent the two ends of the spectrum of thyroid complications following interleukin-2 therapy. Such complications are not uncommon but are poorly documented. We suggest that patients receiving cytokine therapy should be followed up closely for any autoimmune complications.
Adult↗
The presence of Sjögren's syndrome is a major determinant of the pattern of interstitial lung disease in scleroderma and other connective tissue diseases.
A number of patients with scleroderma, Sjögren's syndrome and other connective tissue diseases (CTD) were assessed to ascertain the prevalence of respiratory abnormalities as defined by bronchoalveolar lavage (BAL), standard respiratory function studies and gallium scan of the lung, and the relationship of these abnormalities to the presence or absence of dyspnea. These results suggest that respiratory symptoms are very common in CTD and in scleroderma, particularly if Sjögren's syndrome is also present. Our findings also suggest the presence of 2 patterns of interstitial lung involvement in scleroderma. In scleroderma alone this appears to be characterized by the presence of increased neutrophil proportions in the BAL, decreased DLCO, and no increase in gallium uptake within the lung. Where scleroderma is associated with Sjögren's syndrome, there is an increase in the proportion of lymphocytes in the BAL and respiratory symptoms are very prominent, the latter associated with an increase in gallium uptake within the lung. This suggests that Sjögren's is a major determinant of the pattern of interstitial lung disease seen in CTD.
Bronchoalveolar Lavage Fluid↗
A simple and rapid immunological technique for visualising chromosome-mediated gene transfer (CMGT).
A method is described for visualising chromosome-mediated gene transfer (CMGT) by detecting chromosomes labelled with bromodeoxyuridine (BrdU) using a monoclonal antibody to BrdU. In this experiment, the CCRF-CEM T cell line was grown in the presence of BrdU and the labelled chromosomes were isolated and transfected into human embryonic fibroblasts. Uptake and retention of chromosomes were compared for transfection with either PEG or DMSO treatments. Following transfection the labelled chromosomes could be visualised in recipient cells using a monoclonal antibody to BrdU, followed by immunoperoxidase staining. Chromosome uptake into cells was similar for both DMSO and PEG treatments and was a relatively frequent event; about 1 in 5 recipient cells had labelled material present. This technique can be used to assess the technical aspects of the earliest stages of chromosome-mediated gene transfer.
Antibodies, Monoclonal↗
c-erbB activation in avian leukosis virus-induced erythroblastosis: multiple epidermal growth factor receptor mRNAs are generated by alternative RNA processing.
Avian leukosis virus-induced erythroblastosis results from the specific interruption of the host oncogene, c-erbB, by the insertion of an intact provirus. This insertion results in the expression of two size classes (3.6 and 7.0 kilobases [kb]) of truncated c-erbB transcripts which are initiated in the 5' long terminal repeat of the integrated provirus. Through sequence analysis of erbB cDNA clones we have previously shown that the 3.6-kb activated erbB mRNA contains portions of viral gag and env genes fused to c-erbB sequences (T.W. Nilsen, P.A. Maroney, R.G. Goodwin, F.M. Rottman, L.B. Crittenden, M.A. Raines, and H.-J. Kung, Cell 41:719-726, 1985). In this report we show that the 7-kb mRNA differs from the shorter activated c-erbB mRNA in the length of its 3' untranslated sequence such that the longer mRNA has an extremely long (4.3 kb) 3' untranslated sequence. Additionally, we demonstrate that activated c-erbB mRNA precursors can be processed by alternative splicing to yield mRNAs with viral gag sequences fused directly to c-erbB sequences. Finally, blot hybridization evidence suggests that the two size classes of activated c-erbB mRNA in erythroblastic tissue represent truncated versions of the two c-erbB mRNAs present in normal tissue.
Animals↗
The rabbit C family of short, interspersed repeats. Nucleotide sequence determination and transcriptional analysis.
The C repeat family was first observed in the rabbit beta-like gene family. We have estimated the repetition frequency of the C repeats, determined the nucleotide sequence of three intact members and one truncated member, and have investigated the size, tissue specificity, and intracellular localization of C repeat transcripts. Members of the C repeat family are short (average size of 316 base-pairs) and are repeated about 170,000 times per haploid genome in a widely dispersed pattern. They end in a 3' poly(dA) tract and are flanked by direct repeats that range in size from 8 to 16 base-pairs. The consensus internal control regions for polymerase III transcription are located near the 5' end. Different amounts of C repeat RNA accumulate in a variety of tissues, and most of the transcripts are confined to the nucleus. A heterogeneous distribution of C repeat RNA sizes was found, ranging from about 330 to 8200 nucleotides. These structural and transcriptional properties are similar to those of primate and rodent Alu and Alu-like repeats. However, the C repeats are not similar in sequence to the Alu repeats. Thus two different types of short, interspersed repeats capable of being transcribed and proposed to be transposable elements have now been identified in mammals. The positions of these short repeats in mammalian beta-like globin gene families are not tightly conserved.
Animals↗
Two sequential randomized trials of community participation to recruit women for mammographic screening.
BACKGROUND: If mammographic screening is to reduce mortality from breast cancer, it is essential that a high proportion of the target population attend for screening. In order to achieve this, effective recruitment strategies are needed. This paper reports two trials of recruitment strategies for mammographic screening involving eight communities in rural New South Wales (NSW), Australia. METHODS: Each trial involved two matched pairs of towns in the Hunter Valley region of NSW. Towns were randomly allocated to intervention, receiving either mass media promotion or community participation in Trial 1 and community participation or family physician involvement in Trial 2. RESULTS: In Trial 1, significantly higher attendance rates were observed in the two towns that received the community participation intervention compared with their matched media promotion towns (63% vs 34%, P < 0.001 and 51% vs 34%, P < 0.01). In Trial 2, a significantly higher attendance rate was observed in one town that received the family physician involvement intervention compared with its matched town which received the community participation intervention (68% vs 51%, P < 0.01). There was no significant difference in attendance in the other pair of towns (68% vs 58%, P = 0.11). CONCLUSIONS: Both community participation and family practitioner involvement are more promising strategies for the promotion of attendance at mammographic screening facilities than media promotion alone.
Adult↗