Biomedical subjects

G Hazlehurst

Publications and source records attributed to G Hazlehurst.

7 recordsLinked to original sources

PubMed2004

Leucodepletion for transmissible spongiform encephalopathies.

Transmissible spongiform encephalopathies (TSEs) have been recognised around the world for many years. Creutzfeldt-Jakob disease (CJD), one of the human forms of TSE, has been studied widely and thus far has not proved a great threat to human health. The emergence of two new TSEs--bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt-Jakob disease (vCJD) in humans in the UK--has caused great concern. BSE has had an economic impact and vCJD is a threat to human health. It has been shown that these two diseases are caused by the same prion agent and are linked. Research indicates that vCJD behaves differently to CJD and there is strong evidence to suggest that vCJD is present in lymphoid tissues and B lymphocytes, which presents a theoretical risk that it may be transmitted by transfusion of blood and blood products. To minimise/prevent this risk, the UK government has decided that plasma should be sourced from abroad and has instructed the National Blood Service to leucodeplete all blood and blood products, at a cost of 70 million pounds per annum, although it is not known if this will remove this risk.

Blood Donors↗

PubMed2000

Reducing red blood cell transfusion in elective surgical patients: the role of audit and practice guidelines.

In 1996, we prospectively audited peri-operative transfusion practice in elective surgical patients over a 3-month period. Two-unit transfusions represented 60% of all transfusions. Haemoglobin was measured infrequently prior to transfusion and the main 'trigger' for transfusion was an estimated blood loss in excess of 500 ml. Transfusion guidelines that required the haemoglobin level to be measured immediately before transfusion were introduced. The audit was repeated in 1998; transfusion 'triggers' and the number of transfusions for the two periods were compared. In the second audit, the total number of transfusions decreased by 43%. The mean estimated blood loss associated with a 2-unit transfusion had increased from 608 (373) ml to 1320 (644) ml (p < 0.01) and the estimated haemoglobin concentration after transfusion had decreased from 12.4 (1.8) g.dl-1 to 9.9 (2.4) g.dl-1 (p < 0.01). These results suggest that transfusion guidelines can have a significant impact on clinical practice.

Attitude of Health Personnel↗

PubMed1999

Hepatitis C lookback programme: a single hospital experience.

As part of the national Hepatitis C (HCV) Lookback Programme, HCV-infected donors donating blood after September 1991 were identified and the fate of their previous donations received at a single hospital were traced; 123 of 160 implicated blood components were traceable and transfused. Only 19 recipients were alive and traceable and were tested for HCV. Nine of the 14 recipients (64%) of HCV-positive donations and 2 of 5 recipients (40%) of HCV-indeterminate donations had evidence of HCV infection. Neither the number of donor exposures nor the type of component was predictive of recipient HCV status. Three recipients have chronic active hepatitis. The Hepatitis C Lookback Programme successfully identifies some but not all cases of transfusion-transmitted HCV. Transfusion records, particularly in the medical case notes, should be substantially improved. Many of the traced recipients are young, so that identification of HCV is of great importance.

Adolescent↗

PubMed1993

Impact of aprotinin on blood transfusion requirements in liver transplantation.

A retrospective study was carried out to ascertain the blood bank provision required to support a liver transplant programme and to assess the effect of intraoperative aprotinin on blood product requirements in liver transplant recipients with cirrhosis. Sixty patients with end-stage liver disease underwent 62 consecutive orthotopic liver transplants between October 1988 and January 1991. The total and intraoperative requirements of red cells, platelets and fresh frozen plasma (FFP) were analysed for three groups of liver transplant recipients, those without cirrhosis (n = 15), those with cirrhosis (n = 25) and those with cirrhosis who received intraoperative aprotinin (n = 20). Fifteen without cirrhosis had mean total requirements of 15 units of red cells, 18 units of platelets and 16 units of FFP. Twenty patients with cirrhosis who received intraoperative aprotinin had broadly similar requirements. However, blood product requirements for 25 patients with cirrhosis were significantly greater (46 units of red cells, 41 units of platelets, 43 units of FFP, excluding the seven patients with primary biliary cirrhosis). We conclude that a liver transplant programme can be supported by a teaching hospital blood bank. The use of intraoperative aprotinin significantly reduces blood product requirements.

Adult↗

PubMed1991

Possible mechanism of selective killing of myeloid leukemic blast cells by lymphokine-activated killer cells.

Major histocompatibility complex-unrestricted lymphokine-activated killer (LAK) cells have been proposed as therapy for a variety of hematologic malignancies. Because these cells recognize and kill their targets independently of their antigen specific CD3 receptor, it is unclear how they might discriminate between normal and malignant cells. We now propose one such mechanism for the selective killing of myeloid leukemia blasts. While both CD2+ and CD2- activated killer cells may inhibit the clonogenic growth of myeloid leukemia cells, only the CD2+ subset effectively inhibits the growth of normal myeloid (granulocyte-macrophage and granulocyte) progenitors. This difference appears to reflect differential requirements for cell adhesion molecule recognition between normal and malignant progenitor cells. Inhibition of the growth of normal granulocyte-macrophage colonies by CD2+ LAK cells is blocked by antibodies to the CD2-lymphocyte function-associated antigen 3 (LFA-3) (CD58) cell adhesion system. In contrast, these antibodies have no effect on CD2+ LAK-mediated inhibition of malignant cell clonogenic growth. Instead, antibodies to the LFA-1 (CD11a/CD18)-intercellular adhesion molecule 1 (ICAM-1) (CD54) adhesion system reduce inhibition. These differences correspond to differential expression of the CD54 cell adhesion molecule by normal and malignant myeloid progenitor cells because less than 15% of normal CD34 positive cells are CD54+ while greater than 85% of CD34+ acute myeloid leukemia blasts express the CD54 antigen. LFA-3, the ligand for CD2, is strongly expressed by erythrocytes, and these cells competitively inhibit killing of normal but not malignant clonogenic cells in an analogous way to the effects of monoclonal antibody to the CD2-LFA-3 adhesion system. The operation of this effect in vivo may be a basis for selective cytotoxicity by CD2+ LAK against clonogenic myeloid blast cells, and could be exploited further with infusion of appropriate monoclonal antibodies.

Antigens, CD↗

PubMed1991

Blood product support in patients undergoing chemotherapy and autologous or allogeneic bone marrow transplantation for haematological malignancies.

Three groups of patients with leukaemia and myelodysplasia were assessed with regard to the blood product support they required during their period of bone marrow hypoplasia following treatment. One group received myelo-ablative remission-induction chemotherapy followed by appropriate consolidation therapy (two courses in patients with acute myeloid leukaemia and one or two intensification courses in patients with acute lymphoblastic leukaemia); whilst the other two had 'conditioning' with chemotherapy and radiotherapy prior to autologous bone marrow transplantation (auto-BMT) or T cell depleted allogeneic bone marrow transplantation (allo-BMT). There was no statistically significant difference in blood product requirements between the three groups. However, platelet requirements during remission-induction chemotherapy alone were significantly less than for allo-BMT or auto-BMT. Platelet requirements for patients undergoing auto-BMT were also significantly higher than for patients receiving consolidation chemotherapy; and were required for a longer period than for patients receiving allogeneic-BMT. There was no difference in blood product support between ABO matched and mismatched transplants within the allogeneic group, but the presence of graft versus host disease and/or cytomegalovirus infection did significantly increase the requirements for blood product support.

Adolescent↗

PubMed1989

Endogenously generated activated killer cells circulate after autologous and allogeneic marrow transplantation but not after chemotherapy.

After marrow transplantation, major histocompatibility complex (MHC)-unrestricted natural killer (NK) lymphocytes are among the first cells to appear in the circulation. After T-cell-depleted bone marrow transplantation (TD-BMT), these cells have an activated pattern of target cell killing; they also secrete lymphokines including gamma-interferon (gamma-IFN), interleukin-2 (IL-2), and tumor necrosis factor (TNF) and may have a significant role as a primary defense against viral reactivation and in the elimination of residual host malignancy. We studied 43 patients with hematologic malignancy, treated by allogeneic TD-BMT, autologous nondepleted BMT, or chemotherapy alone to investigate (a) the mechanisms underlying the generation of these activated killer cells, (b) the range of conditions under which they are produced, and (c) their surface phenotype. We showed that gamma-IFN-secreting activated killer cells with the capacity to kill MHC-nonidentical NK-resistant targets are generated 4 to 6 weeks after either allogeneic TD-BMT or autologous BMT but do not appear after treatment with chemotherapy. Production therefore is not owing to T-cell depletion per se or to host donor alloreactivity, nor is it caused by stimulation by alloantigens contained in blood product support since no significant difference exists between allograft and chemotherapy patients in the number of units of blood platelet support given in the posttreatment period. Because most patients had no evidence of stimulation from virus reactivation/infection, the phenomenon of activation therefore appears to represent posttransplant immune disregulation following repopulation of the host immune system with lymphoid subsets derived exclusively from blood and marrow. Activated killing is predominantly mediated by the CD16+ CD3- subset, but substantial activity remains in the CD16- CD3+ cell fraction. Monoclonal antibodies (MoAbs) that block interaction with class-I MHC molecules at the level of target cell (W6/32 anti-HLA class I) or effector cell (CD8) do not inhibit killing by CD16- CD3+ cells. Activated killer cells may contribute to the lower risk of relapse after marrow transplantation as compared with intensive chemotherapy.

Adolescent↗