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Biomedical subjects

R Sparrow

Publications and source records attributed to R Sparrow.

9 recordsLinked to original sources

Right of the living dead? Consent to experimental surgery in the event of cortical death.

Ravelingien et al have suggested that early human xenotransplantation trials should be carried out on patients who are in a permanent vegetative state (PVS) and who have previously granted their consent to the use of their bodies in such research in the event of their cortical death. Unfortunately, their philosophical defence of this suggestion is unsatisfactory in its current formulation, as it equivocates on the key question of the status of patients who are in a PVS. The solution proposed by them rests on the idea that it should be up to people themselves to determine when they should be treated as dead. Yet the authors clearly believe (and state) that patients who are in a PVS are in fact dead. Finally, given the public good that their proposal is intended to achieve, the moral importance they place on the consent of a person to the use of his or her body in research is ultimately only defensible in so far as this consent represents the wishes of a living person. It is thus only a gentle caricature of their position to suggest that according to their account, consent to participation in xenotransplantation research is a "right of the living dead". The equivocation by Ravelingien et al on the question of whether these people are living or dead means that they avoid confronting the implications of their argument. The solution proposed by Ravelingien et al to the problem of how we should proceed with xenotransplantation research is therefore not as neat as it first seems to be.

Attitude to Death↗

Bone marrow stromal function from patients after bone marrow transplantation.

A two-stage long-term bone marrow culture (LTBMC) has been used to assess haemopoietic supporting ability from patients following allogeneic bone marrow transplantation (BMT). Irradiated confluent LTBMCs derived from recipients following BMT were recharged with flow cytometry sorted CD34+/CD38- cells from normal BM donors. The output of granulocyte/macrophage colony-forming cells (GM-CFC) in the non-adherent fraction of the cultures was monitored weekly until output ceased. Patient stromal cell function was determined by comparing the percentage of the total cumulative GM-CFC output to the output from normal control stroma. Neutrophil recovery was rapid and complete early in the post-transplant period. However, in contrast, GM-CFC recovery was significantly reduced in all patients up to 5 years after BMT. In 58% of patients studied following BMT the BM stroma is considerably compromised in its ability to support early uncommitted haemopoietic cells contained within the CD34+/CD38- cell fraction of normal BM. Bone marrow stroma from BMT recipients exhibited severe deficits in their abilities to support primitive haemopoietic cells and in some patients this effect lasted for several years. While the growth of stroma from patients following BMT was severely delayed and often incomplete, characterisation of cells types using APAAP techniques did not show significant differences in proportion when compared with normal cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

ADP-ribosyl Cyclase↗

Elevated serum homocysteine as a predictor for vitamin B12 or folate deficiency.

Tissue deficiency of vitamin B12 and folate results in an increase in serum homocysteine (sHcy). We have measured sHcy in patients with reduced serum vitamin B12 and/or red cell folate (RCF) to determine its usefulness as a discriminant for the diagnostic interpretation of reduced vitamin levels. Of 3846 patients who had serum vitamin B12 and RCF assayed, 335 (9%) had reduced vitamin levels. Multivariate analysis showed a significant association between sHcy and serum creatinine (p = 0.0001), positive intrinsic factor (IF) antibody or neutrophil hypersegmentation (NHS) (p = 0.001), increased MCV (p = 0.014) and low RCF (p = 0.025) but no relationship with the level of serum vitamin B12 or haemoglobin. After censoring the patients with renal impairment (n = 54), the distribution of the remaining 72 patients with elevated sHcy was 37/151 (25%) with low serum vitamin B12 with or without low RCF and 35/130 (27%) with low RCF alone. sHcy correctly identified response to vitamin therapy in 33/35 (94%) patients who had adequate parameters to assess response. The positive predictive values of IF antibody/NHS, macrocytosis and/or low RCF for elevated sHcy were 100% and 34% respectively. Twenty-four percent of patients with a low serum vitamin B12 and elevated sHcy had no abnormal haematologic parameters as determined by the routine laboratory staff. These data suggest that the usefulness of measuring sHcy in a routine diagnostic setting is limited and a careful review of the peripheral blood for macrocytosis and NHS plus determination of RCF may be a more cost-effective process than sHcy assay in most instances to determine the presence of tissue deficiency.

Adult↗

Expression of CD45 isoforms in chronic B-cell leukaemias.

CD45 isoform expression was studied in 204 cases of B-cell lymphoproliferative disease, including 162 chronic lymphocytic leukaemia (CLL). In almost half the samples tested, CD45R0 was co-expressed with CD45RA, unlike normal B-cells, which express only CD45RA, except at terminal stages of differentiation. In a small number of cases CD45R0 was the dominant isoform expressed. No correlation could be discerned either with Binet or RAI staging in CLL or with disease type CLL, prolymphocytic leukaemia (PLL) or hairy cell leukaemia (HCL). Comparison of CD45 isoform expression with other markers showed no correlation with apparent maturational status of the cells involved.

Antigens, CD↗

Clinical application of a rapid, functional assay for multidrug resistance based on accumulation of the fluorescent dye, fluo-3.

A rapid and simple functional assay for P-glycoprotein (Pgp) using flow cytometry to measure the accumulation of the flurophore fluo-3 has been applied to samples from patients with B-cell chronic lymphocytic leukaemia (B-CLL). Peripheral blood lymphocytes from 37 patients with B-CLL were studied for Pgp. Pgp expression, using MRK-16, a monoclonal antibody recognising an external surface epitope of Pgp, was detected in 92% of patients with B-CLL. The functional assays for Pgp expression were positive in 78 and 59% of patients using the fluo-3 and doxorubicin (dox) assays, respectively. When compared with the MRK-16 assay, the fluo-3 assay had a sensitivity of 82% compared to a sensitivity of 56% for the dox assay (P = 0.004). The specificity of the fluo-3 and dox assays could not be evaluated because of the low number of MRK-16 negative CLL cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Acquired amegakaryocytic thrombocytopenia: report of a case and review of literature.

We describe a 55-year-old female with acquired amegakaryocytic thrombocytopenia who has been successfully treated with antithymocyte globulin. In-vitro studies assessing megakaryocytopoiesis in the presence of the patient's plasma and peripheral blood adherent cells showed normal or increased stimulation. This patient brings to 30 the number of adult cases of acquired amegakaryocytic thrombocytopenia now reported in the English literature. Review of this material suggests that it may be more common than has been appreciated. Several pathogenic mechanisms, especially immune mechanisms, have been identified; good, sustained remissions have been achieved in eight patients who were treated with immunosuppressive agents.

Antilymphocyte Serum↗

Murine megakaryocyte colony stimulating factor: its relationship to interleukin 3.

A protocol for the partial purification of murine megakaryocyte colony stimulating factor from WEHI-3 cell conditioned medium is described. The procedure involving separation by anion exchange chromatography and molecular sieving on Sephadex G100, gave a 260-fold purification over starting material, as determined by in-vitro megakaryocyte colony formation. Fifty percent of maximum colony numbers were obtained at a dose of 1 microgram protein/ml. Electrophoretic analysis of the partially purified preparation followed by silver nitrate staining revealed four major protein bands with apparent molecular weights of 67 Kd, 43 Kd, 38 Kd and 28 Kd. All megakaryocyte colony stimulating activity and interleukin 3 activity was found in the 22-25 Kd fraction from a preparative SDS-polyacrylamide gel using non-reducing conditions, a molecular weight range that coincided with the 28-Kd molecule obtained when reducing conditions were employed.

Animals↗