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Biomedical subjects

J K Duguid

Publications and source records attributed to J K Duguid.

At least 19 recordsLinked to original sources

A case of unexplained mild Rh (D) haemolytic disease in utero.

This report describes the case of a patient with a history of HDN complicated by fetal losses, in which the alloantibody in this particular pregnancy did not appear to cause HDN in utero. No protective HLA-DR antibodies could be demonstrated, and transport of IgG across the placenta appeared to be normal. The infant's red cells possessed a normal D antigen and his mononuclear phagocyte system appeared unimpaired. However, the number of molecules of IgG bound in vivo per fetal red cell was below the level usually associated with significant haemolysis and HDN.

Adult

Haemolytic disease of the newborn due to anti-M.

A patient with haemolytic disease of the newborn (HDN) due to anti-M which required exchange transfusion is described. Anti-M antibodies are usually assumed to be naturally occurring and to consist of immunoglobulin M (IgM); many however have an immunoglobin G (IgG) component. In view of this and the described occurrence of HDN, recommendations are made regarding the management of a pregnancy in which anti-M antibodies are detected.

Adult

Autologous bone marrow transplantation for myeloma patients using PNA- and CD19-purged marrow rescue.

A new method of in vitro bone marrow purging using a lectin and monoclonal antibody in combination has been used for the first time in vivo. Two patients with advanced myeloma were treated with high-dose melphalan and total body irradiation and then rescued with autologous bone marrow which had been purged in vitro to remove malignant cells by using a combination of a plasma cell-binding lectin (peanut agglutinin, PNA) and the anti-B lymphocyte monoclonal antibody anti-CD19, bound to magnetised microspheres. Both patients showed rapid engraftment of the purged bone marrow and remain well 36 and 46 months later with normal bone marrow morphology, although one patient still has a low level of circulating paraprotein. This is a promising form of therapy for what has been an invariably fatal condition.

Adult

Prothrombin fragment F1 + 2: correlations with cardiovascular risk factors.

Plasma prothrombin fragment F 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT), fibrinogen and factor VII were related to variables associated with increased cardiovascular risk in 86 plasma donors (49 male and 37 female). F1 + 2 had a log-normal distribution and increased significantly with age and body mass index (BMI). Significantly, higher F1 + 2 levels were found in smoking compared with non-smoking males and in indolent males compared with males taking regular exercise. Higher levels were found in subjects with a parental history of ischaemic heart disease than in those lacking such a history. F1 + 2 correlated strongly with increasing cholesterol in males. Fibrinogen was significantly higher in male smokers than male non-smokers but did not vary with age or BMI. Factor VII correlated strongly with cholesterol and to a lesser extent with fibrinogen, F1 + 2 and BMI, but not with smoking. F1 + 2 correlated more closely with risk factors for cardiovascular disease than fibrinogen and factor VII, and consistently reflected the difference in cardiovascular risk when correlated with risk factors which have markedly different effects between the sexes. It promises to be a useful predictive marker of ischaemic heart disease.

Adult

Red cell antibody screening and identification: a comparison of two column technology methods.

Two commercial column techniques for use in antibody screening and identification procedures were tested in parallel with 1000 random samples sent for ante-natal serological investigation. The DiaMed ID microtyping system uses a sephadex gel contained in microtubes, either neutral or impregnated with anti-human globulin (AHG), for use in two-stage enzyme methods and LISS indirect antiglobulin testing (IAT) respectively. The Ortho Biovue technique consists of a slurry of micro glass spheres which act as the filter to retain haemagglutination reactions within the matrix. Columns containing AHG also possess a macromolecular density barrier to prevent test serum from passing into the column and neutralising the AHG. Both systems offer the advantage of 'no-wash' IAT, which minimises the potential for problems and errors associated with conventional spin-tube techniques. In this comparison of the two column methods, antibody detection rates were found to be similar and the sensitivity of both methods was comparable, although the Biovue technique was prone to exhibit equivocal results, particularly in the IAT.

Antibodies

A method for clinical purging of myeloma bone marrow using peanut agglutinin as an anti-plasma cell agent, in combination with CD19 monoclonal antibody.

Previous studies have shown that the lectin peanut agglutinin (PNA) binds bone marrow plasma cells in the majority of patients with myeloma and does not bind to normal haemopoietic progenitors. This lectin has been used in combination with anti-CD19 monoclonal antibody (moAb) in a system for purging myeloma bone marrow. This has now been scaled up for application to ex vivo treatment of large volumes of bone marrow suitable for autologous bone marrow transplantation. Four bone marrow harvests from patients with myeloma containing 9.5 +/- 4.9% plasma cells were depleted of erythrocytes and mature granulocytes by Ficoll separation using the Haemonetics V50 cell separator. The mononuclear fraction was then purged with magnetic beads coated with PNA and anti-CD19 moAb. The system proved highly efficient with removal of all detectable plasma cells and CD19+ cells. Average mononuclear cell recovery following purging was 71% of the concentrated marrow with 78% yield of CFU-GM. Normal progenitor recovery related to patients' weight is predicted to be adequate for haemopoietic reconstitution following ablative chemoradiotherapy. This system is therefore feasible for large-scale clinical purging.

Adult

Immunisation of staff of a regional blood transfusion centre with a recombinant hepatitis B vaccine.

Medical, nursing, laboratory and other staff of the Mersey Regional Blood Transfusion Centre at risk of acquiring hepatitis B were vaccinated against the virus with a recombinant vaccine. Altogether, 86% staff developed greater than 10 mIU/ml antibody to hepatitis B virus surface antigen after immunisation but the proportion was lower in older staff. After a further injection of vaccine was given to poor and non-responders the overall proportion responding rose to 93%. The difference in response between the sexes was significant. Women had a higher rate of response and, among those persons responding, women developed a higher concentration of antibody.

Adult

Clinical evaluation of the effects of storage time and irradiation on transfused platelets.

Platelet concentrates stored for up to 5 days at room temperature or irradiated with 15 Gy immediately prior to transfusion were evaluated for their ability to increase the platelet count in thrombocytopenic patients. Platelets irradiated with a dose of 15 Gy immediately prior to transfusion achieved corrected increments (CI) at 1 and 20 h after transfusion no different from those achieved by non-irradiated platelets. Storage for 5 days reduced the mean 1-hour CI to 5.7 compared with a mean of 12.3 achieved by platelets transfused after only 1-day storage (p = 0.008). Similarly, the frequency of a repeat transfusion being indicated within 24 h increased with increasing storage time (p = 0.005).

Blood Platelets

Cold agglutinins in haemophiliac boys infected with HIV.

Eleven haemophiliac boys infected with HIV were screened for irregular red cell antibodies and were compared with nine haemophiliac boys who did not have antibodies to HIV. Seven (64%) of the children who had antibodies to HIV also had cold agglutinins, mostly of anti-I specificity, compared with one (11%) of those who did not have antibodies to HIV. The children with antibodies to HIV and cold agglutinins had a significantly increased mean IgM concentration. The presence of cold agglutinins was not correlated with T4 lymphocyte count, symptoms of HIV infection, serum beta 2 microglobulin concentrations, concentrations of IgG or IgA, or with the evidence of past infection with cytomegalovirus or Epstein-Barr virus.

Adolescent

Blood group chimaerism: a possible further example.

A blood group chimaera is described whose red blood cells exhibit a dual population of group A1 and O, in the proportions 20% and 80% respectively. These results could also indicate a blood group mosaic of the Amos type, but family studies, secretor and transferase investigations on this patient suggest that blood group chimaerism of unestablished type is more likely. There was no further evidence of chimaerism found during cytogenetic investigations, immunoglobulin allotyping or studies of red cell enzyme systems. Blood group chimaeras were previously thought to be rare, as dual red cell populations and the resulting mixed-field agglutination patterns are not always easy to recognise. This case is the second example of chimaerism found within two years in a single routine laboratory, appearing to confirm the view that chimaerism is not as uncommon as previously thought.

ABO Blood-Group System

Developing techniques in blood transfusion.

Expansion of transfusion medicine has led to an increasing awareness of the importance of its practice. Specialists in this branch of haematology whose main aim is to provide adequate and safe supplies of blood (and blood products) and to ensure these are used appropriately, are increasingly aware that to do this efficiently requires the development and utilization of new laboratory and technical procedures. Review of cross-matching techniques has led to the introduction of more rapid methods using low ionic strength saline. Use of monoclonal antibodies for blood grouping has made use of new technology, whilst allowing scarce human plasma to be used more appropriately for therapeutic purposes. Similarly, the implementation of a more rational approach to blood ordering, as in a maximum surgical blood-order schedule, allows for the more efficient use of donor blood. The use of microtitre plates for grouping and cross-matching techniques allows for speed and economy in the transfusion laboratory. Their use is also associated with increased automation and computer use. The possibility of using solid-phase techniques, monocyte-macrophage assays and antibody-dependent cellular cytotoxicity assays introduces new techniques differing markedly from time-honoured liquid-phase serology methods. The application of flow cytometry, which has already been shown to be useful in many aspects of haematology, is also of benefit in the field of blood transfusion science. Safety of blood transfusion is an important aspect of its practice and has led to the introduction and development of screening tests for donor blood to exclude infection risks from such organisms as HIV-1, hepatitis B and non-A, non-B hepatitis. Another approach to ensure the safety of transfused blood has been increased usage of autologous transfusion by means of both predeposit donation and intraoperative cell salvage.

Antibodies, Monoclonal

Red cell antigens and renal transplantation.

Donor-specific transfusion was performed with and without cyclosporine between haplomismatched relatives prior to living-donor renal transplantation. Red cell antigen mismatching was not taken as a contraindication to DST. Of 80 patients included in the trial; eleven were ABO-mismatched, 15 were Rh(D)-mismatched, and a further 11 were transfused in the presence of atypical red cell antibodies (anti-D, -C, -Fya, -Kell -N, -H/I -I, -P1, -Wra). Patients were randomized to receive cyclosporine (10 mg/kg) daily during DST or not (control group). The presence of atypical red cell antibodies, with the exception of Rh anti-D, did not appear to influence DST or renal transplantation. DST did not act as a primary stimulus to Rh anti-D production but stimulated preexisting anti D levels. ABO mismatching did not appear to influence DST or subsequent renal transplantation except in one group A [corrected] patient who received group O [corrected] blood and cyclosporine. This patient developed a severe, but self-limiting, autoimmune hemolytic anemia due to auto-anti A antibodies. A similar group A patient in the control group developed an auto-antibody with no clinical sequelae. The influence of cyclosporine on the development of this auto-antibody is uncertain. We conclude that, with the exception of preexisting anti-D antibodies, minor red cell antigen disparities should not preclude pretransplant conditioning with donor-specific transfusions.

ABO Blood-Group System