Imatinib-induced cytogenetic remission in chronic eosinophilic leukaemia.
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Benzamides↗
Biomedical subjects
P Cannell
Publications and source records attributed to P Cannell.
Delivery of postgraduate dental education to meet the needs of general dental practice --a case study.
In order for dental practices to gain the maximum benefit from an educational opportunity such as a course or workshop, it is important that the training received meets the needs of these practices and is delivered appropriately. This paper provides an account of an educational initiative undertaken within the Eastern deanery in 2003 and 2004, 'Essex Promoting Infection Control' (EPIC), which set out to establish training needs in infection control within general dental practices across Essex and then to design and deliver learning events to meet these needs.
Dental Staff↗
A phase II study of Rituximab in rheumatoid arthritis patients with recurrent disease following haematopoietic stem cell transplantation.
Haematopoietic stem cell transplantation (HSCT) has been used recently as an effective therapy in patients with resistant rheumatoid arthritis (RA). Although disease control occurs in the majority of cases, recurrence is common, often coinciding with B-cell reconstitution. We hypothesized that Rituximab, a monoclonal anti-CD20 antibody, would have activity in this group of patients. We treated 10 RA patients (8F:2M, median age 46.5 years), who had recurrent disease post HSCT. All patients received two doses of Rituximab 1 g, 2 weeks apart with no major adverse sequelae and were followed for 12 months. A total of eight out of 10 patients experienced major clinical responses as measured by the American College of Rheumatology (ACR) criteria, with 50-70% improvement in disease parameters. Responses were equivalent to previous responses attained with HSCT. Disease responses were maximal at 4-8 months post Rituximab and correlated with B-cell lymphopenia and a reduction of rheumatoid factor titre. Disease recurrence occurred in 6/9 responders within 12 months and four patients were subsequently retreated, with major responses again attained. This study provides further evidence that B-cell depletion leads to a significant improvement in disease activity in patients with severe RA and provides data for future trials of HSCT and Rituximab therapy.
Adult↗
Prolonged profound abciximab associated immune thrombocytopenia complicated by transient multispecific platelet antibodies.
Patients receiving abciximab occasionally develop transient severe thrombocytopenia within a few hours of receiving the drug. Thrombocytopenia has been reported to resolve within 10 days of abciximab administration, but in this case profound thrombocytopenia lasted 21 days before a slow spontaneous recovery. Management was complicated by the presence of HLA antibodies and the transient production of antibodies directed at major platelet glycoproteins IIb/IIIa, Ib/IX, and Ia/IIa. The patient remained refractory to platelet transfusion and two courses of intravenous gammaglobulin for the duration of her admission.
Abciximab↗
Investors in people: what is it all about?
Recently, there has been a proliferation of press releases from organizations recognized as Investors in People including the BDTA, the DPB, the BDA and many individual dental practices. Indeed, the number of dental practices recognized as Investors in People has more than doubled in the last six months. What is this sudden interest in Investors in People within the dental profession all about? This article is a guide to what the Investors in People (IiP) standard is, what relevance it has to dental practice and what benefits can be gained from working towards this standard. I have used my own experiences in gaining the standard in our dental practice to act as an example throughout the article.
Dental Staff↗
Effects of glycosylated recombinant human granulocyte colony-stimulating factor after high-dose cytarabine-based induction chemotherapy for adult acute myeloid leukaemia.
The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 microg per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5 x 10(9)/l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 x 10(9)/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P= 0.015) and a trend to reduced number of days with fever >38.0 degrees C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects.
Acute Disease↗
Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome.
Previous retrospective studies have demonstrated improved outcome in patients whose donors were matched for non-HLA markers in the MHC as well as for HLA genes. Forty patients receiving transplants from unrelated donors were typed prospectively for HLA and non-HLA markers. Non-HLA markers near HLA-B (beta-block markers) and in the DRB1 introns (delta-block markers) were used to assess MHC match between donors and recipient. Patients whose donors were matched at the beta- and delta-blocks had improved event free survival (63%) compared to patients whose donors were mismatched at one or both blocks (25%) (p < 0.05). Patients whose donors were matched at the beta-block had significantly less severe acute graft versus host disease (p < 0.05). In order to investigate the basis for improved outcome block matching was correlated with HLA matching as determined by DNA sequencing. Beta-block matching was highly correlated with matching for exons 2 and 3 of HLA-B but less so for HLA-C. Delta-block matching was highly correlated with matching for exon 2 of HLA DRB1. It is concluded that matching for non-HLA markers in the MHC improves matching for HLA genes. Further studies are required to determine whether matching for non-HLA markers improves outcome to a greater extent than matching for the HLA genes alone.
Adolescent↗
Molecular detection of minimal residual disease in adult and childhood acute lymphoblastic leukaemia reveals differences in treatment response.
Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of patients with B lineage acute lymphoblastic leukaemia (ALL). Two hundred and three bone marrow samples from 54 patients (33 adults and 21 children) were analysed by PCR within specific time-points after diagnosis (ie 1, 2-3, 4-6 and 7-12 months) using FR1 and JH primers (fingerprinting with a sensitivity > or =1:5 x 10[3]). CDR3-derived allele specific oligoprimers (ASO to achieve a sensitivity between 1:10[4] and 1:10[5]) were applied to 12 children and 18 adults, while size of CDR3 region, oligoclonality and background problems prevented their application to the remaining patients. All patients were followed clinically for > or =24 months. Thirty adults and 16 children presented as newly diagnosed ALL, while the remaining eight patients were analysed in first or subsequent relapse. Patients destined to relapse showed a higher proportion of positive tests (> or =50%), particularly after 1 month, than in the remission group, irrespective of age. Among patients staying in remission, a decrease in MRD-positive tests occurred during the first 12 months in both age groups. However, the proportion of positive tests dropped below 15% at a later stage in adults (4-6 months) than in children (2-3 months). Among children, only patients destined to relapse were MRD positive beyond 1 month, with the exception of only one patient, still positive at 2-3 months in the remission group. The difference in MRD positivity between relapse and remission patients was statistically significant in children (P < 0.03) at any time of testing, but only at 4-6 months in adults (P < 0.01). These data suggest that resolution of MRD in ALL occurs more rapidly in children compared to adults, particularly within the first 6 months. Children and adults, studied in first or subsequent relapse, showed a higher proportion of positive tests during reinduction compared to newly diagnosed patients.
Adolescent↗
Mobilization of predominantly Philadelphia chromosome-negative blood progenitors using cyclophosphamide and rHUG-CSF in early chronic-phase chronic myeloid leukaemia: correlation with Sokal prognostic index and haematological control.
Mobilization of Philadelphia chromosome (Ph) negative blood progenitors was attempted in 23 newly diagnosed chronic myeloid leukaemia (CML) patients using a regimen of cyclophosphamide (CY) 5 g/m2 and rHUG-CSF 150 microg/m2 daily. This regimen was well tolerated with no major adverse events reported. More than 2 x 10(6)/kg CD34+ cells were collected in 21 patients (91%). Predominantly Ph-negative mobilization (0-25% Ph-positive) was seen in 30% of cases overall and was confined to patients with a Sokal prognostic score < 1 (7/11 with Sokal score <1; 0/12 with Sokal score > or = 1). Within the low Sokal index group, a low WBC count pre-mobilization and a low WBC nadir both correlated strongly with Ph-negative mobilization (P = 0.006 and 0.02 respectively). Five of 19 patients receiving at least 6 months of Roferon A therapy post mobilization achieved a major cytogenetic response; all five patients were Ph-negative mobilizers. Therefore CML patients can be divided into a good-prognosis group in whom predominantly Ph-negative progenitors can be mobilized using a regimen of moderate intensity if haematological control is achieved pre-mobilization, and a poor-prognosis group for whom predominantly Ph-positive cells are mobilized with this regimen regardless of haematological control.
Adult↗
Recruitment of CD34+ cells during large-volume leukapheresis.
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Adult↗
Collection and recruitment of CD34+ cells during large-volume leukapheresis.
Although sufficient progenitor cells for hematopoietic rescue following high-dose therapy may be obtained in a single leukapheresis, the majority of patients require multiple procedures. In an attempt to minimize the number of leukapheresis and maximize collection efficiency, we undertook large-volume leukapheresis in 17 patients with a variety of hematologic malignancies. Twenty-four procedures were performed over a 6-h period, with a mean of 21 L of blood processed. By employing a modified collection set, three separate 2-h collection bags were analyzed for a number of variables. CD34+ cells are collected at a steady rate throughout the procedure, with no evidence of exhaustion of progenitor cells. There was evidence of progenitor cell recruitment, with 1.4-fold more CD34+ cells in the collected product than were present in the blood at the beginning of the procedure. Initiation of leukapheresis was based on the blood CD34+ count, and this value was strongly correlated with the number of CD34+ cells in the collected product. The procedure is safe and relatively simple and minimizes the number of leukaphereses required to collect adequate progenitors for autologous transplantation.
Adolescent↗
Correlation of bone marrow minimal residual disease and apparent isolated extramedullary relapse in childhood acute lymphoblastic leukaemia.
We have used a polymerase chain reaction (PCR) technique capable of detecting one leukaemic cell in 10(5) normal cells to monitor minimal residual disease (MRD) in a retrospective study of childhood ALL. We were particularly interested in comparing MRD findings in patients in long-term remission, bone marrow relapse and apparent isolated extramedullary relapse (EMR). Archival slides were initially studied from 21 patients. However, on subsequent analysis, only 15 patients were informative at the molecular level. All seven patients with EMR had evidence of MRD in the bone marrow at the time of relapse. Five of the seven also had evidence of bone marrow MRD prior to EMR. In one of the seven patients, MRD was not detected in a bone marrow sample studied 5 months prior to EMR. The remaining EMR patient was not studied prior to EMR. Of five patients who remained in long-term remission (mean 144 months), three did not have detectable MRD at the end of induction therapy (2 months) and all five were MRD-negative at the end of treatment (36 months). This contrasts with the three patients who relapsed in the bone marrow at 8, 15 and 88 months post-treatment and who had evidence of MRD at the end of therapy.
Bone Marrow↗
Procoagulant states and stroke.
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Blood Coagulation↗