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Biomedical subjects

M Deane

Publications and source records attributed to M Deane.

At least 19 recordsLinked to original sources
PubMed2001

Systematic review of laparoscopic surgery for colorectal malignancy.

BACKGROUND: We set out to evaluate the current literature on the use of laparoscopic surgery for malignant colorectal disease and identify its place in current practice. METHODS: We performed a systematic review of the literature that included papers published from January 1991 to March 1997. Inclusion criteria were used to select the most robust studies. The quality of each study was assessed against predefined criteria and weighted according to hierarchy of evidence and sample size. RESULTS: The published literature was found to be low in the hierarchy of evidence. Of the 157 studies located, only 42 papers were found to be of sufficiently high quality to be included in the review. Only 13 of these 42 papers concentrated specifically on malignant colorectal disease. We noted the following findings: The average age of patients was 63.2 years. The most frequently reported contraindication to laparoscopic surgery was obesity. Conversion rate to open procedure varied between 1.5% and 48%. The most common postoperative complication was wound infection. Thirty-day mortality varied between 0 and 5.1%. Disease stage and pathology were poorly reported. Patient recovery benefits varied. It was not possible to identify the effectiveness, safety, survival outcome, or cost of laparoscopic surgery for colorectal malignancy in comparison to open surgery. CONCLUSIONS: Six years after the first report of laparoscopic surgery, studies low in the hierarchy of evidence continue to be reported. This reflects a lack of control following the introduction of this new technology. The majority of reports continue to be feasibility studies. The variable nature and content of the literature demonstrate the lack of standardization and the absence of an agreed core minimum data set. The benefit of laparoscopic surgery for malignant colorectal disease remains unclear. Until the mechanisms of port site recurrences are elucidated and long-term data on survival outcomes become available, laparoscopic surgery for malignant disease should be carried out only in the context of a large, multicenter randomized controlled trial.

Carcinoma↗
PubMed2001

A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation.

The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.

Acute Disease↗
PubMed1999

Locality commissioning: how much influence have general practitioners really had?

This paper investigates the various models of locality commissioning in relation to the participation of general practitioners (GPs), and explores the perceived successes of locality commissioning in the 15 health boards in Scotland and 13 health authorities in the Northern and Yorkshire Region of England. A postal questionnaire was sent to 190 individuals involved in commissioning, and semi-structured interviews with GPs (n = 31) and health authority managers (n = 41) were undertaken in each of the 28 health authorities. Seventy-five per cent of the health authorities had introduced some form of locality commissioning. Five types of locality commissioning organization were identified on the basis of the level of GP influence over decisions. All GP responders identified benefits resulting from their involvement in the process but only 27% of health authority responders did so. Most benefits related to improved professional relationships, not to service changes. On the whole, locality commissioning does not appear to have resulted in major changes to contracts or services.

England↗
PubMed1998

Acute skin GVHD following syngeneic BMT for CLL.

A 41-year-old woman received a syngeneic BMT for CLL and subsequently developed acute skin GVHD. Transfusion-related allogeneic GVHD was excluded on the basis of an unchanged HLA type in circulating lymphocytes. Short tandem repeat PCR was used to confirm syngeneicity between donor and recipient. The patient had a personal and family history of autoimmune disease which may have made her particularly susceptible to development of syngeneic GVHD. The distinction between allogeneic and syngeneic or autologous GVHD is important because of therapeutic implications.

Acute Disease↗
PubMed1998

FLAG-idarubicin and allogeneic stem cell transplantation for Ph-positive ALL beyond first remission.

We describe a single centre experience of eight consecutive patients with relapsed or refractory Ph+ ALL treated with the FLAG/idarubicin regimen followed by BMT or PBSCT. Following FLAG/idarubicin, one achieved a partial response and seven CR. All patients subsequently received allogeneic transplants: one sibling BMT, three matched unrelated (MUD) BMT and four sibling PBSCT. Two patients received second transplants with PBSC from their original BM donors following FLA/Ida with no further conditioning. Three patients are alive in CR 9, 24 and 32 months after transplant. Seven of eight patients had a cytogenetic response following FLAG/Ida induction and one of seven became bcr-abl negative. All eight patients had a complete cytogenetic response following transplant. Four of five assessable patients became p190 bcr-abl negative after transplant; three of these subsequently relapsed. Both patients with the p210 bcr-abl transcript remained bcr-abl positive in CR after transplant. FLAG/Ida was well tolerated and appears to be effective in inducing remission in relapsed Ph+ ALL. The use of FDR-containing chemotherapy without further conditioning prior to PBSCT deserves further study in heavily pre-treated patients and, in patients with relapsed ALL following BMT, may be a safer option than DLI (donor lymphocyte infusion) by avoiding the associated risk of aplasia.

Adolescent↗
PubMed1997

The in vitro detection of anti-leukaemia-specific cytotoxicity after autologous bone marrow transplantation for acute leukaemia.

Anti-leukaemia activity after allogeneic bone marrow transplantation has been studied extensively but its antigen specificity and effector cell phenotype remain unknown. Here we report a study in three recipients of autologous bone marrow transplantation done as part of the treatment for acute leukaemia, in whom we were able to detect innate specific anti-leukaemia activity post-transplant. One patient maintained selective cell-mediated cytolytic activity against her autologous leukaemic cells in the absence of cytolysis of her normal bone marrow mononuclear cells (BMMC). She remains in complete remission 3 years after ABMT for acute myeloid leukaemia (M5). A second patient was transplanted for acute lymphoblastic leukaemia and had detectable anti-leukaemia activity up to 20 weeks post-ABMT. At this point anti-leukaemia activity could no longer be demonstrated and the patient suffered a relapse 2 weeks later. A third patient was transplanted for AML (M4 Eo) and lacked detectable leukaemia-specific immune reactivity at 1, 3 and 6 months post-ABMT. She relapsed 6 months after her ABMT and returned to complete remission after further chemotherapy. She commenced treatment with alpha interferon and regained NK function. Furthermore, she developed high level cytolytic activity against her autologous leukaemic cells in the absence of activity against her remission bone marrow samples. She remains in complete remission 17 months after her initial relapse. This is the first report of an apparent association between in vitro leukaemia-specific cytolytic activity in individual patients after ABMT and clinical outcome. It encourages the theory that autologous immunomodulation may be useful in the future treatment of leukaemia.

Acute Disease↗
PubMed1997

Quantification of CMV viraemia in a case of transfusion-related graft-versus-host disease associated with purine analogue treatment.

We report a patient who developed transfusion-associated graft-versus-host-disease (GvHD) and concurrent cytomegalovirus (CMV) infection, both complications thought to be related to severe T lymphocyte depletion induced by treatment with a purine analogue drug, fludarabine. CMV viraemia was detected by qualitative PCR and the viral load in positive samples was measured using a fully quantitative PCR assay. This quantitative assay enabled the evaluation of the efficacy of antiviral interventions based on the qualitative PCR result. The case illustrates the risks associated with the use of purine analogue drugs, as well as the value of quantitative CMV PCR assays for monitoring CMV infection in immunocompromised patients.

Acute Disease↗
PubMed1996

The value of the Short Form 36 score in the outcome assessment of subarachnoid haemorrhage.

This pilot study aimed to establish if the Short Form 36 (SF-36) provides clinically relevant information about patient outcome which is not detected using the Glasgow Outcome Score (GOS) A retrospective postal questionnaire survey of all patients operated on for subarachnoid haemorrhage at the Leeds General Infirmary between March 1991 and December 1992 of perceived health status was undertaken 6-18 months following surgery. Of the respondents with a GOS score of Good the SF-36 score was reduced in each domain. The most notable score reduction was in the role-function physical domain where the mean score was 48 percent compared with a population norm of 88 percent. It was concluded that the SF-36 has a role in the evaluation of patients following surgery for SAH and may have a place in their routine assessment. Further work in a larger group of patients is required.

Activities of Daily Living↗
PubMed1994

Fetal marrow suppression after maternal chemotherapy for leukaemia.

A preterm baby, whose mother received chemotherapy for acute leukaemia during pregnancy, required intensive care because of profound anaemia and neutropenia. Haemopoietic progenitor cell studies showed fetal marrow suppression. Those caring for such mothers and babies should know the possible serious effects chemotherapy for malignancies can have on a developing fetus. Long term follow up of the baby is imperative.

Acute Disease↗
PubMed1994

Distinctive features of immunoglobulin heavy chain variable region gene rearrangement in multiple myeloma.

We have analysed the rearranged Ig heavy chain (IgH) genes in a series of 28 cases of multiple myeloma (MM), in order to extend the study of Ig heavy chain variable (VH) gene usage in B lymphoid malignancies and to explore the ontogenic compartment from which transformed precursor cells arise in this disease. We were able to amplify 28 rearranged alleles by polymerase chain reaction from 23 of these cases, using a common joining region (JH) amplimer together with a panel of VH family-specific amplimers. The pattern of VH family usage was similar to that reported in normal peripheral blood B cells with infrequent usage of VH5 and VH6 genes. However, nucleotide sequence analysis of 17 IgH alleles revealed rearrangement of other VH family members, closely related to known developmentally regulated VH genes, some of which are known to be associated with autoimmune specificities. In contrast to previous findings on more immature B lineage malignancies, the rearranged genes diverged extensively from consensus germline sequences, consistent with somatic mutation. These findings support the hypothesis that the major proliferating precursor in MM arises at, or following a stage of T cell-dependent germinal centre proliferation in lymphoid follicles.

Base Sequence↗
PubMed1994

Uptake of carbon monoxide in Los Angeles commuters.

The uptake of carbon monoxide in Los Angeles commuters was measured by determining carbon monoxide concentrations in expired air before and after commuting. Estimates of exposure were made by determining carbon monoxide concentration in air collected within each car during each trip. There was a definite increase in expired air carbon monoxide concentration during the morning commute trip, but not during the afternoon trip. No consistent differences by geographic area were noted. Multiple correlation analysis showed that the post-commuting values depended more upon precommuting expired air values than upon carbon monoxide measured within the car. Smokers showed consistently higher values of carbon monoxide than nonsmokers, and the effect of smoking was several times greater than that of exposure to carbon monoxide levels experienced during commuting.

Adolescent↗
PubMed1993

Immunoglobulin VH4 gene usage in B lymphoid leukaemias.

VH4 gene rearrangements occur in a similar proportion of cases of B lineage acute lymphoblastic leukaemia (ALL) and B chronic lymphocytic leukaemia (B CLL). However, there may be differences in the pattern of VH4 gene usage between these disorders as is the case for VH1 gene rearrangements. To examine this, we analysed the sequences of 24 PCR-amplified clonal VH4 gene rearrangements from a series of 15 cases of ALL and nine cases of CLL. Five distinct groups of genes were rearranged, three of which (represented by V2-1, V71-2/V71-4, V4.21) have been described in rearranged form in normal B lymphoid tissues. The most frequently rearranged gene was V4.21 which is strongly associated with autoimmune reactivity. V71-2, V71-4 and V2-1 were more frequently rearranged in CLL than ALL. The remaining two groups (represented by V4.33, V4.35) have not previously been described in rearranged form. One of these, V4.35, was seen only in ALL rearrangements. Both V4.35 and a VH1 gene, 20P3, which is also preferentially rearranged in ALL, are located at the 3' end of the VH locus. The location of these genes suggests that their rearrangement may be developmentally regulated in ALL. The findings in this study confirm restricted repertoires of IgH gene rearrangement in ALL and CLL. Characterization of IgH repertoires provides a means of correlating these transformed B cell populations with normal B cell developmental compartments. Moreover, the distinctive repertoires in ALL and CLL may reflect important differences in the ontogenic timing and microenvironmental milieu of tumourigenesis in these disorders.

Base Sequence↗
PubMed1993

The genetic basis of human VH4 gene family-associated cross-reactive idiotype expression in CD5+ and CD5- cord blood B-lymphocyte clones.

In a recent study we have observed a high frequency expression of cross-reactive idiotypes encoded by genes from the relatively small VH4 family of immunoglobulin heavy chain genes in cord blood B-lymphocyte lines. Furthermore, we have demonstrated a selective pattern of expression of two VH4-associated cross-reactive idiotype (CRI) in B-lymphocyte lines established from CD5+ and CD5- cord blood B-lymphocytes. There was a restricted expression of one CRI marker recognized by the 9G4 monoclonal antibody in lines established from CD5+ B-lymphocytes but not in those established from the CD5- population. In the current study we examine the molecular basis for the selective pattern of CRI expression. Nucleotide-sequence analysis of functional immunoglobulin heavy chain (IgH) gene rearrangements in three CD5+ lines expressing the CRI recognised by 9G4 reveal that all use a single gene from the VH4 family, the V4.21 gene. However, all three lines have distinct third complementarity determining regions (CDR3) implying different clonal origins. In contrast, four cord blood cell lines (two established from CD5+ B-lymphocytes) expressing the CRI recognized by MoAb Lc1 have functional IgH gene rearrangements involving two different genes from the VH4 family, the V71-4, and V2-1 genes. Antigen specificity analysis reveals that all three 9G4-reactive lines produce antibodies that react with the I and/or i red blood cell carbohydrate antigens. These data suggest that the distinction in VH4 gene use in CD5+ B-lymphocytes in cord blood results from a selection process in vivo that shapes the repertoire of CD5+ B-lymphocytes. This study extends recent observations that the monoclonal anti-CRI antibodies 9G4 and Lc1 are markers of two distinct subgroups of proteins encoded by two subsets of genes within the VH4 family. Furthermore, it appears that amino acid residues in framework region one and complementarity determining region two are critical for the expression of the cross reactive idiotypes and the serological distinction between the two subgroups of proteins.

Amino Acid Sequence↗
PubMed1993

Child accident data: accessible and available?

The accessibility, availability and content of health service data on accidental injuries occurring in childhood was investigated. Death data, admission data and Accident and Emergency (A&E) data were examined. Considerable problems were experienced with the availability of routine data, and the available information was found to be limited by the nature and content of the data collected by computerized systems. Data were limited both in terms of providing information to the local Accident Prevention Working Group and for the monitoring of preventive activity. It was also determined that none of the data were being audited. It was concluded that there is a need for national agreement concerning both cause of injury coding and severity coding.

Abstracting and Indexing↗
PubMed1992

Specificity and idiotope expression of IgM produced by CD5+ and CD5- cord blood B-cell clones.

Epstein-Barr virus (EBV)-immortalized monoclonal B-cell lines were established from CD5+ and CD5- cord-blood B cells. IgM from many of both CD5+ and CD5- clones reacted with IgG-Fc, ssDNA, and a variety of other autoantigens. More CD5+ B cells that used light chains of the kappa isotype reacted with IgG-Fc and ssDNA than kappa-bearing CD5- B cells. Because many of the clones reacted with IgG-Fc, they were analyzed for the expression of cross-reactive idiotypes (CRI) associated with rheumatoid factor and cold agglutinin paraproteins using murine antibodies (mAb) recognizing V kappa and VH subgroup-associated determinants. Expression of the V kappa IIIb sub-subgroup-associated idiotope recognized by 17.109 mAb was expressed at significantly higher frequency (32%; p less than 0.05) and IgM antibodies derived from the CD5+ compared with the CD5- clones (5%). Both CD5+ and CD5- clones expressed the RF paraprotein-associated idiotope recognized by G8 mAb to the same extent. Similar results were obtained using binding to SpA as a marker of VH III family usage. Furthermore, no differences in frequency of expression of RF paraprotein-associated idiotopes recognized by B6 and/or D12, and characteristic of some antibodies using VH III family genes, were found between the CD5+ and CD5- populations. Although a higher than expected frequency of VH IV-gene expression was demonstrated (around 30%) in both CD5+ and CD5- cells, there were differences in expression of CRI recognized by mAb Lc1 and R2.1A2 with specificities for two VH IV subfamilies. While some CD5+ and CD5- clones were identified in which their IgM reacted with mAb Lc1, only CD5+ clones were recognized by another mAb R2.1A2. Analysis of the relationships between antigen specificities and V kappa- and VH-family gene usage indicated that auto- or polyreactivity was not associated with V kappa III nor any particular VH family. The higher frequency of the V kappa IIIb sub-subgroup-associated idiotope recognized by 17-109 in the CD5+ clones and the association of CD5+ B cells with the VH IV subfamily recognized by mAb R2.1A2 and 9G4 may suggest that CD5+ B cells in cord blood are expanded as a result of recruitment within the fetal environment.

Animals↗
PubMed1992

Is drinking water related to spontaneous abortion? Reviewing the evidence from the California Department of Health Services Studies.

Because preliminary data suggested a relation between risk of spontaneous abortion and tapwater consumption during pregnancy, the California Department of Health Services included questions on prenatal water consumption in all reproductive studies conducted between 1982 and 1988. Results from four of these five retrospective data bases suggest that women abstaining from tapwater or drinking bottled water during the first trimester of pregnancy may be at reduced risk of spontaneous abortion. Fetal resorption frequencies seen in an accompanying toxicology study were consistent with these epidemiologic findings, although not conclusive. Tap and bottled water samples from these study areas were analyzed for agents that might account for these findings. Differences in trace element composition and biological activity were observed, but the reproductive significance of these differences is unknown. This paper presents an overview of these studies, which are presented in detail separately. Three alternative explanations for these findings--bias, chance, and causality--are reviewed.

Abortion, Spontaneous↗