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Biomedical subjects

M Watts

Publications and source records attributed to M Watts.

At least 37 records · Page 2Linked to original sources
PubMed1998

Feasibility of multidrug resistance (MDR-1) gene transfer in patients undergoing high-dose therapy and peripheral blood stem cell transplantation for lymphoma.

We have performed a pilot study of MDR-1 gene transfer in patients receiving CD34-selected peripheral blood stem cell (PBSC) transplant for lymphoma. To ensure minimum engraftment thresholds and facilitate CD34 purification, mobilisation of > 2 x 10(6) CD34 cells/kg was a condition for recruitment. Of 11 patients counselled for study entry, only five achieved this target in a single apheresis. In three consenting patients, purified CD34 cells were exposed to A12M1 MDR-1 retroviral supernatant for 6 h, cryopreserved then thawed and readministered following ablative chemotherapy. No delay in engraftment was observed, although one patient received additional back-up cells. Gene transfer was demonstrated by polymerase chain reaction (PCR) for vector-derived MDR-1 cDNA sequence in all cases. Analysis of peripheral blood and bone marrow cells after transplant has, however, shown no evidence of in vivo gene transfer with a follow-up of 12, 15 and 18 months. The effect of MDR-1 substrate drugs has not yet been tested as all patients remain in clinical and radiological remission of their lymphoma. These results confirm the difficulty of achieving in vivo gene transfer in human haemopoietic cells and indicate major logistical constraints in PBSC mobilisation in patients with relapsed and resistant disease in whom initial studies are appropriate.

Adolescent↗
PubMed1998

Occupational gender segregation: index measurement and econometric modeling.

Empirical studies of gender segregation by occupation must be founded on rigorous measurement procedures. There appears to be a consensus that any index used in the analysis of time-series or international cross-section employment data must be either margin-free or decomposable to yield a margin-free component. On the other hand, Charles and Grusky (1995) advocate the use of multiplicative log models from which a margin-free odds ratio can be derived. In this paper, I contrast the construction and interpretation of the index of dissimilarity and the Karmel-MacLachlan index with the multiplicative modeling of gender segregation and the associated log index.

Employment↗
PubMed1998

The analysis of sex segregation: when is index measurement not index measurement?

In their paper in this issue, Grusky and Charles (1998) make a number of dubious claims about the measurement and interpretation of sex segregation. First, they incorrectly claim that only log-odds measures yield margin-free measures of segregation. Second, the estimation and testing of a limited class of log-linear models does not provide an independent test of the appropriateness of a log-odds ratio index to measure segregation. Their estimation in forms them of the statistically justifiable degree of occupational disaggregation, not whether a log-odds ratio is superior to, say, a linear index in the measurement of segregation. Finally, their index A is beset with problems of interpretation, not withstanding their arguments, and their additional measures, AW and AB, suffer similar problems. Grusky and Charles are, however, correct in arguing that measurement procedures should be margin-free. Further, I concur with the view that the adoption of a single annual summary measure of segregation cannot be justified, because it is premised on the assumption that individual occupations, or groups of occupations, exhibit similar trends in sex segregation.

Female↗
PubMed1997

Imprecision of counting CFU-GM colonies and CD34-expressing cells.

Determinations of committed haemopoietic progenitor cells, namely CFU-GM (colony-forming unit-granulocyte/macrophage) and of CD34-expression haemopoietic cells as assessed by multiparameter flow cytometry are routine diagnostic tools in haemopoietic cell therapy. Generally, the tests are used to optimise the timing and management of cytapheresis and to assess the engraftment potential of the harvested cells. Both measurements, however, are at best surrogate markers, as an adequate routine test which effectively assesses the short- and long-term repopulating haemopoietic cell is not available. Nonetheless, cell threshold doses have been established. Above these thresholds rapid engraftment is almost invariable but below these thresholds the outcome is variable. In this study we have focussed on the imprecision in counting haemopoietic cells, as assessed as CFU-GM and as CD34-expressing cells. The data on both tests have been analysed from six European institutions. The coefficient of variation in CFU-GM colony counting was about 30%, whereas the coefficient of variation in flow cytometric counting of CD34-expressing cells was about 10%. These data suggest that the technical imprecision in enumerating progenitor cells, particularly CFU-GM, at low levels, might make a major contribution to the clinical variability observed after transplantation of sub-threshold progenitor cell dose.

Antigens, CD34↗
PubMed1997

Successful engraftment of haploidentical stem cell transplant for familial haemophagocytic lymphohistiocytosis using both bone marrow and peripheral blood stem cells.

Familial haemophagocytic lymphohistiocytosis (HLH) is a disease with a very poor prognosis unless patients receive a bone marrow transplant. It is often difficult to find an HLA-matched donor and haploidentical familial donors may be considered. The main complication of this type of transplant is graft rejection. We describe a patient with familial HLH who received a haploidentical transplant using both mobilized peripheral blood and bone marrow stem cells in an attempt to overcome graft rejection by increasing the stem cell dose. The peripheral blood stem cell inoculum was CD34 enriched using a Cellpro column and T-cell depleted by Campath-1M, the patient received conditioning for a matched sibling donor transplant with the addition of Campath 1G. There was rapid and full engraftment and the patient remains disease free at 5 months. This technique may be applicable for other fatal inborn errors in the absence of an HLA-matched donor.

Bone Marrow Transplantation↗
PubMed1996

In-vitro clonogenicity of mobilized peripheral blood CD34-expressing cells: inverse correlation to both relative and absolute numbers of CD34-expressing cells.

The determination of CD34-expressing cells by multiparameter flow cytometry is now widely used to estimate the reconstitution potential of cells harvested by cytapheresis for peripheral blood stem cell and progenitor cell transplantation. There is a correlation between the number of CD34-expressing cells collected and committed progenitor cells (CFU-GM and BFU-E) capable of forming colonies in vitro, but there is considerable variation in the proportion of CD34-expressing cells capable of clonogenic growth. The data in this study of 782 cytapheresis samples indicates that there is a negative correlation between the clonogenicity of the CD34-expressing cells and the absolute number or the proportion of CD34-expressing cells within the harvest. In 116 samples the proportion of CD34-expressing cells co-expressing the CD45-RA-antigen (a subset of CD34-expressing cells which includes virtually all clonogenic cells in terms of CFU-GM) was determined, but this did not help to identify the clonogenicity of a given sample. These findings may have clinical relevance, particularly when mobilization is judged to be relatively poor or when a good harvest is to be divided for multiple high-dose procedures.

Antigens, CD34↗
PubMed1995

The polymerase chain reaction in the demonstration of monoclonality in T cell lymphomas.

AIMS: To evaluate polymerase chain reaction (PCR) amplification of T cell receptor (TCR) beta and gamma chain genes as a means of demonstrating monoclonality in T cell lymphomas using histological samples; to compare the performance of PCR with Southern blot analysis. METHODS: TCR-beta, TCR-gamma and immunoglobulin heavy chain (IGH) genes were analysed using PCR in 55 cases of T cell lymphoma (28 frozen tissue and 27 paraffin wax embedded samples), diagnosed using morphological and immunohistochemical criteria. The 28 frozen samples were subjected to Southern blot analysis using TCR-beta, TCR-gamma and IGH gene probes. Twenty five B cell lymphomas and 21 non-neoplastic lymphoid tissue samples were used as controls. RESULTS: Using TCR-beta PCR, monoclonality was detected in 24 (44%) of 55 T cell lymphomas compared with 43 (78%) of 55 using TCR-gamma PCR and in 82% with both techniques. Five (9%) of 55 T cell lymphomas were IGH PCR positive. None of the non-neoplastic lymphoid control samples were PCR positive. All B cell lymphomas showed a polyclonal pattern with TCR-beta PCR while a single B cell lymphoma was positive using TCR-gamma primers. With TCR-beta PCR, a monoclonal result was seen in 12 (43%) of 28 frozen samples of T cell lymphoma, compared with 23 (82%) of 28 using Southern blot analysis. With TCR-gamma PCR, 19 (68%) of 28 frozen tissue samples were positive, compared with 26 (93%) of 28 using Southern blot analysis. A single case showed IGH rearrangement by Southern blot analysis. CONCLUSION: TCR-gamma PCR should be the method of choice for analysis of clonality in paraffin wax embedded sections of lymphoproliferative lesions, as TCR-beta PCR has a high false negative rate. Southern blot analysis remains the most successful technique when sufficient fresh tissue samples and resources are available.

Base Sequence↗
PubMed1994

Interpersonal learning in groups: an investigation.

The dissatisfaction of patients with communication in health care has largely been addressed by providing more communication skills training. Research into why skills training might be ineffective has identified various factors, which include organizational resistance, personal defences against anxiety and a need for personal reflection and support. In one college of nurse education small group discussion and reflection had become established practice for students in their first and second clinical experience. The groups met once weekly and were facilitated by a nurse teacher. Discussion was unstructured and focused on the nurse's interpersonal relationship with his or her patients. This project examined one such group and sought to examine the use of small group reflective discussion by nurses about their patients as a means of improving interpersonal communication. The research was conducted over a period of 6 months with nine student nurses meeting once weekly during their first two episodes of clinical experience. Kelly's personal construct theory was used and two repertory grids were constructed by the group. One grid examined processes and change in intrapersonal construing, and the other grid examined processes and change in construing about certain patients. These grids were completed by the students at the beginning and at the termination of the groups. Notes were taken after each group meeting, which recorded impressions and processes; these were discussed once weekly with supervision. The notes were analysed using a grounded theory methodology. The results show some changes in patterns of constructing in relation to self which indicate an increase in anxiety and reluctance to self-reflect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Platelet loss during plasma exchange is unaffected by in-line filters.

15 patients underwent plasma exchange using a standard 170-microns in-line filter with or without an additional 40-microns microaggregate filter in the return circuit. The mean platelet count fall immediately after plasma exchange in 15 patients was (54 +/- 6) x 10(9)/l and 48 h later was (23 +/- 8) x 10(9)/l representing a mean total platelet loss immediately after plasma exchange of (253 +/- 31) x 10(9) with no difference in the 40-microns filtered procedures. The mean platelet loss in the discarded plasma was (60 +/- 8) x 10(9), and a mean of 52 x 10(9) platelets were recovered from machine harness washings. The platelet loss in the removed plasma and in the harness therefore accounted for only 42-44% of the total loss of platelets. The inclusion of 40-microns microaggregate filters did not reduce platelet loss, and it is therefore unlikely that the thrombocytopenia is induced by reinfused microaggregates. It is likely that platelets are activated in the machine and sequestered in the spleen.

Humans↗
PubMed1992

Fc gamma RII, but not erythropoietin or GM-CSF, mediates calcium mobilization in fetal hemopoietic blast cells.

A proportion of fetal liver hemopoietic blast cells express Fc gamma RII, and addition of the anti-Fc gamma RII monoclonal antibody CIKM5 induces a rise in calcium in these cells in suspension. Although these cells are thus capable of mobilizing intracellular calcium in response to surface receptor mediated events, neither granulocyte-macrophage colony-stimulating factor (GM-CSF) nor erythropoietin produced detectable changes in intracellular calcium ion concentration in these cells.

Antibodies, Monoclonal↗
PubMed1991

Aggregation of subclinical autonomic nervous system dysfunction and autoantibodies in families with type I diabetes.

The purpose of our study was to evaluate the occurrence of autonomic nervous system autoantibodies (ANS) in the nondiabetic family members of insulin-dependent (type I) diabetic subjects. We studied 24 families, including 45 nondiabetic parents and 53 nondiabetic siblings of a type I diabetic proband. One hundred one nondiabetic population control subjects were also studied. Stored sera from nondiabetic family members and control subjects were evaluated for the presence of complement-fixing (CF) adrenal medullary antibodies (CF-ADM), sympathetic ganglia antibodies (CF-SG), and vagus nerve antibodies (CF-V) by indirect immunofluorescence. HLA-DR3 and -DR4 typing was performed on 42 nondiabetic family members and 104 diabetic subjects. One or more CF-ANS were in 45 of 93 (40%) nondiabetic family members compared to 2 of 70 (2.8%) control subjects. CF-SG were in 28 of 92 (30%) family members compared to 0 of 101 control subjects (P = 0.0001). CF-V were in 25 of 95 (26%) family members compared to 0 of 76 control subjects (P = 0.0001). CF-ADM were in 10 of 83 (12%) family members compared to 2 of 70 (2.8%) control subjects (P = 0.056). There was no HLA-DR3 or HLA-DR4 association with ANS. Subclinical autonomic dysfunction was demonstrated in 3 of 4 family members with autoantibodies compared to 0 of 4 family members without autoantibodies.

Adolescent↗