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Biomedical subjects

S McCann

Publications and source records attributed to S McCann.

At least 55 records · Page 3Linked to original sources
PubMed1996

Empowering the patient in the consultation: a pilot study.

This study examined the efficacy of a brief written intervention for primary care patients, designed to increase their level of participation in the consultation. Patients given the intervention leaflet (N = 59) were compared with those given a control leaflet (N = 61) on various consultation process and outcome measures. Psychological and sociodemographic data were also obtained to determine whether these influenced the effects of the intervention. The results showed that the intervention group had significantly longer consultations and asked more questions than the controls. Younger patients and those from social classes 1 and 2 were more likely to benefit from the intervention, but locus of control and self-efficacy scores were not particularly helpful in predicting outcomes. No differences in patient satisfaction were found nor were any negative effects on the doctor observed. A number of explanations are explored and some directions for future research are discussed.

Adolescent↗
PubMed1996

The repression of apoptosis by activated abl oncogenes in chronic myelogenous leukaemia.

The formation of the unique fusion gene, bcr-abl, and the resultant increase in abl tyrosine kinase activity, is seen as the major driving force in the initiation of chronic myelogenous leukaemia (CML). The deregulation of abl tyrosine kinase activity, brought about by the binding of a portion of the Scr molecule to the SH2 regulatory domain of abl, appears to play a role in promoting resistance to drug-induced apoptosis. Thus the large increase In mature myeloid cells seen in CML could be the direct result of the suppression of apoptosis by the bcr-abl fusion protein. The role and contribution of apoptosis in the progression of CML and the possible role of antisense oligonucleotides to the bcr-abl gene as therapeutic agents is discussed.

Apoptosis↗
PubMed1995

Repression of the c-myb gene by WT1 protein in T and B cell lines.

The c-myb gene is primarily expressed in immature hematopoietic cells, and it is overexpressed in many leukemias. We have investigated the role of negative regulatory sites in the c-myb promoter in the Molt-4 T cell line and in the DHL-9 B cell line. A potential binding site for either the EGR-1 or WT1 protein was identified by in vivo footprinting in the 5'-flanking region of c-myb in a region of negative regulatory activity in T cells. We showed by electrophoretic mobility shift assay and electrophoretic mobility shift assay Western that WT1, EGR-1, and Sp1 bound to this site. A mutation of this site which prevented protein binding increased the activity of the c-myb promoter by 2.5-fold. In the DHL-9 B cell line, this site was nonfunctional; however, we found a potential EGF-1/WT1 site located more 3' in a region of negative regulatory activity. We showed that WT1, EGR-1, and Sp1 bound to this site, and that mutation of this site increased the activity of the c-myb promoter by 3.2-fold. Cotransfection of a WT1 expression vector repressed the activity of the c-myb promoter in both cell lines, and this repression was relieved when the EGR-1/WT1 sites were removed. Cotransfection of either an EGR-1 or Sp1 expression vector had no significant effect on the activity of the c-myb promoter. We conclude that WT1 is a negative regulator of c-myb expression in both T and B cell lines.

Animals↗
PubMed1993

Meiotic recombination in an Irish family with beta-thalassaemia.

Using the technique of allele-specific priming of the polymerase chain reaction (PCR), the C-T substitution in codon 39 was identified as the cause of beta-thalassaemia in an Irish family. Analysis of the restriction fragment length polymorphisms (RFLPs) in the beta-globin gene cluster established linkage of the beta-thalassaemia mutation to a particular beta-haplotype but indicated that a recombinational event had occurred in the paternal chromosome in the younger of two affected children. Non-paternity was excluded by DNA fingerprinting analysis with hypervariable minisatellite probes. This is the fourth case of recombination in the beta-globin gene cluster to be reported. The event has occurred 5' of the polymorphic RsaI site at position -550 bp upstream of the beta-globin gene mRNA Cap site, within the 9.1-kb region that has been shown to be a hot spot for recombination in the beta-globin gene cluster.

Base Sequence↗
PubMed1993

Bone marrow transplantation for acute myeloblastic leukaemia: an EBMT Leukaemia Working Party prospective analysis from HLA-typing.

The optimal post-remission therapy for patients with acute myeloblastic leukaemia remains controversial. Allogeneic bone marrow transplantation, autologous bone marrow transplantation, and consolidation chemotherapy are the major options. In order to evaluate their respective value the European Group for Bone Marrow Transplantation conducted a prospective registration study. Patients with newly diagnosed acute myeloblastic leukaemia were registered at the time of HLA-typing and intention to treat in case of presence or absence of an HLA-identical donor was recorded. 27/79 (34%) patients HLA-typed at diagnosis had an identical donor identified. The estimated survivals at 3 years from HLA-typing were 44% and 21% among patients with or without HLA-identical donor, respectively (P = 0.02). 22/26 (85%) patients for whom allogeneic bone marrow transplantation was intended were transplanted but only 15/47 (32%) patients for whom autologous bone marrow transplantation was intended were indeed transplanted (P < 0.001). The survival was 50%, 29% and 17% (P = 0.004) for patients treated with allogeneic bone marrow transplantation, autologous bone marrow transplantation, or chemotherapy, respectively. 40/68 patients HLA-typed in first complete remission had an HLA-identical donor. The estimated 3-year survival among patients typed in first remission with and without HLA-identical donors was 42% and 35% (n.s.), respectively. This technique of early patient registration illustrates the problems of patient selection during the course of the disease and might be used as a complement to randomized trials when comparing bone marrow transplantation and other treatment options.

Adolescent↗
PubMed1993

Relapse of aplastic anaemia after immunosuppressive treatment: a report from the European Bone Marrow Transplantation Group SAA Working Party.

This study was designed to determine the incidence of relapse and factors predictive for relapse in 719 patients with severe aplastic anaemia (SAA) after immunosuppressive treatment (IS). Patients developing myelodysplasia or acute leukaemia after IS, and patients receiving a transplant, were excluded from this analysis. Response was defined as reaching complete independence from transfusions, relapse was defined as becoming again transfusion dependent. This criteria was validated by similar figures when using other 'relapse criteria' such as drop in neutrophil or platelet counts. Of 358 patients responding to IS. 74 patients relapsed after a mean time of 778 d after treatment. The actuarial incidence of relapse is 35.2% at 14 years after IS. The risk for relapse was higher in patients responding within 120 d from IS (48%) compared to patients responding between 120 and 360 d (40%) and only 20% for slow responders (> 360 d from IS) (P < 0.00001). In multivariate analysis this factor still proved significant (P < 0.0001). The mean time between diagnosis and treatment was significantly longer in patients relapsing compared to patients who did not relapse (260 v 134 d, P = 0.037). Relapse was not predicted by the severity of the disease, age, and sex. In 39 of the 74 relapsing patients a second response could be achieved. Responses after relapse were associated in univariate analysis with early response to previous IS and early occurrence of relapse. The actuarial survival of patients not relapsing is significantly better than survival of patients relapsing (79.8% v 67.1%, P = 0.0024). However, the actuarial survival of 39 relapsing patients who responded again to IS was similar to patients not relapsing (86%) and significantly better than in 35 patients not reaching a second response after relapse (49.3%, P = 0.0015). This study indicates that relapse is a relevant problem in the treatment of aplastic anaemia, and does have an impact on overall survival. Prospective studies of immunosuppressive regimens, looking at responses, should also address this problem in the future.

Adolescent↗
PubMed1993

Treatment of aplastic anaemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party.

134 patients with acquired aplastic anaemia (AA) were given HALG 15 mg/kg/d for 5 d and methylprednisolone for 1 month, and randomized to receive (n = 69) or not (n = 65) oxymetholone 2 mg/kg/d p.o. daily for 4 months. Early mortality (< 120 d) was comparable in the two arms 12/69 (17%) and 11/65 (17%), and correlated with the severity of the disease (39%, 10% and 6% respectively in patients with neutrophil counts (PMN) < 0.2, 0.2-0.5, > 0.5 x 10(9)/l). The response rate at 120 d was significantly greater in patients receiving androgens (56% v 40%; P = 0.04); it was 68% v 48% (P = 0.02) in patients surviving 120 d, and 78% v 27% (P = 0.03) in females with PMN less than 0.5 x 10(9)/l. In a multivariate Cox analysis on patients with less than 0.5 x 10(9)/l PMN, the probability of responding without androgens was reduced compared to the androgen treatment arm (P = 0.05). Survival was comparable in the two groups (71% v 65%). It was superior (74% v 50%), but not significantly (P = 0.1) in females with PMN < or = 0.5 x 10(9)/l receiving androgens. Side-effects, including biochemical abnormalities and virilization, could be controlled and were reversible. In conclusion, the addition of androgens to HALG and methylprednisolone as first line treatment of aplastic anaemia significantly improves the response rate at 4 months, particularly in females with low neutrophil counts, although there is no significant effect on short-term survival. The reversible side-effects warrant the use of androgens as an adjunct to the first course of ALG in females with severe AA.

Adolescent↗
PubMed1993

Successful second unrelated donor BMT in a child with juvenile chronic myeloid leukaemia: documentation of chimaerism using the polymerase chain reaction.

A 3-year old child with juvenile chronic myeloid leukaemia received a T cell-depleted BMT from a male unrelated donor. There was early graft failure associated with increasing splenomegaly and hypersplenism. Splenectomy was performed 53 days post-transplant and was followed by autologous marrow recovery with return of leukaemia. A second unrelated donor BMT was performed 9 months later using T cell-replete marrow from a similarly matched female donor. Grade 2 GVHD involving the skin and gut responded to treatment with steroids. Chimaerism was assessed using Y-specific polymerase chain reaction (PCR) and microsatellites. Samples taken at the time of splenectomy showed no donor marrow engraftment but there was significant engraftment in the spleen. Following the second transplant, donor-type haematopoiesis was documented using a panel of microsatellite probes. The patient remains well 6 months after transplant. Splenectomy should be considered prior to transplant in patients with significant splenomegaly and hypersplenism. Partial chimaerism in the spleen, but not bone marrow, post-BMT, has not previously been documented. PCR technology is a useful and highly sensitive way to assess chimaerism post-BMT and is informative in sex-matched cases, whilst the small amount of material required is advantageous in paediatric patients.

Bone Marrow Transplantation↗
PubMed1992

A multicentre survey of serum calcium levels in patients with malignant diseases.

Serum calcium and albumin levels were measured in 255 patients with a confirmed diagnosis of malignant disease. The average serum calcium and albumin levels were similar to those reported in an earlier larger American survey. Only 6/255 patients were above the normal range of corrected serum calcium and one patient was sufficiently hypercalcaemic (corrected serum calcium at least 2.8 mmol/L) to be included in a trial of oral clodronate therapy. The incidence of hypercalcaemia in this survey is considerably lower than that reported in the published literature (5-10%). A much larger proportion of patients (21/255) were hypocalcaemic. Serum albumin was depressed in 25/255 cases and elevated in 2/255 cases.

Calcium↗
PubMed1992

Bone marrow transplantation for acute myeloid leukemia: the EBMT experience. A prospective analysis from HLA-typing. The EMBT Leukemia Working Party.

In 1990, 4,234 BMT were performed in Europe; 2,097 autologous BMT (388 AML) and 2,137 allogeneic BMT (494 AML). Although an established therapy with leukemia free survival (LFS) at five years of 41% +/- 5% (EBMT results) its value compared to alternative therapies remains controversial. During the year 1985, the EBMT conducted a prospective evaluation study. In 12 centres 168 patients with AML were registered at the time of HLA-typing. Basic patient data and treatment intention were recorded. 79 patients were HLA-typed at diagnosis. 68 patients in 1st CR and 21 at other stages. Follow-up of these patients was obtained as of January 1, 1991. Three-year LFS is 44% for patients with an HLA-identical donor and 21% for those without (p = 0.02). Of the 68 patients HLA-typed in first CR, 40 had an HLA-identical donor and 28 no donor. Three-year LFS is 42% and 35%. resp. (n.s.). The difference in results between patients typed at diagnosis and first CR patients illustrates the problem of selection. We conclude that patient registration early in the disease can give insight into the process of selection. Allogeneic BMT incorporated prospectively at diagnosis into therapy offers a survival advantage for patients in this age category compared to alternative therapies.

Acute Disease↗
PubMed1992

Childhood leukaemia in Ireland.

In response to professional and public concern about health consequences, in particular cancer risk, from previous and current levels of ionising radiation in the Irish Sea, a study of incidence and mortality from acute lymphoid leukaemia (ALL) and other lymphoid malignancies in children was undertaken. Overall rates were similar to those found in other western populations and distribution of high rates was quite random over the country as a whole. There was a small but significant excess in incidence of ALL for the years 1974-76 in a narrow three mile wide strip along the east coast. It is not possible in the context of this study to postulate aetiological factors which might explain this finding.

Acute Disease↗
PubMed1990

Treatment with marrow transplantation or immunosuppression of childhood acquired severe aplastic anemia: a report from the EBMT SAA Working Party.

A total of 304 children under the age of 15 years with acquired severe aplastic anemia (SAA) received immunosuppressive therapy (IS) (n = 133) or a matched bone marrow transplant (BMT) (n = 171). The projected 10-year survival is 48% and 63% respectively (p = 0.002). Results following BMT have improved considerably over the years from 49% in 1970-80, to 70% in 1981-83 (p = 0.002) and to 81% between 1984-88 (p = 0.08). Other favorable prognostic factors are the use of cyclosporin A (p = 0.004), no previous therapy (p = 0.006) and early BMT (p = 0.009). In multivariate analysis only the year of treatment proved significant (p = 0.02). In contrast, results of IS are greatly dependent on the severity of pre-treatment neutropenia with survival of 56% versus 37% for neutrophils more or less than 0.2 x 10(9)/l (p = 0.003). Poor survival was associated in univariate analysis with female sex (43%), post-hepatitis SAA (37%), children not receiving androgens (38%) and patients younger than 5 years (35%), especially if associated with a low neutrophil count (11%). In multivariate analysis only the degree of neutropenia proved significant (p = 0.005). These results suggest that IS is a satisfactory alternative therapy for children with moderately SAA in the absence of an HLA-identical sibling, although BMT remains the treatment of choice. In children under 5 years with very SAA, results with IS are so poor that a search for an unrelated matched donor is justified as early as possible.

Actuarial Analysis↗