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Biomedical subjects

M R Howard

Publications and source records attributed to M R Howard.

At least 55 records · Page 3Linked to original sources
PubMed1993

Sea blue histiocytosis: a common abnormality of the bone marrow in myelodysplastic syndromes.

AIMS: To determine whether myelodysplastic syndromes (MDS) are associated with sea blue histiocytosis in the bone marrow. METHODS: A retrospective review of bone marrow aspirates from 35 patients presenting consecutively with MDS and from 20 patients with each of the following: normal marrow appearance (routine staging for non-Hodgkin's lymphoma), polycythaemia rubra vera, immune thrombocytopenic purpura (ITP), chronic myeloid leukaemia (CML) in chronic phase. RESULTS: Sea blue histiocytes were present in the marrow in 12 of 35 cases of MDS and occurred in large numbers in three of these cases. Sea blue histiocytes varied in the degree of cytoplasmic granularity and some cells were intermediate in appearance between classic sea blue histiocytes and pseudo-Gaucher cells. Sea blue histiocyte granules additionally stained positively with Sudan black and periodic acid schiff. Sea blue histiocytes occurred only in the presence of marrow hypercellularity. Their presence did not correlate with FAB subtype, degree of dyserythropoeisis, or megakaryocyte numbers. No sea blue histiocytes were found in the normal marrow or polycythaemia cases. In ITP sea blue histiocytes were seen in two of 20 cases and in chronic myeloid leukaemia in eight of 20 cases. CONCLUSIONS: Sea blue histiocytes are a common cytological feature in the bone marrow of patients with MDS. As other disorders frequently associated with marrow sea blue histiocytes are relatively rare MDS is probably the most common cause of this phenomenon in a northern European population.

Aged↗
PubMed1992

Regional transfusion centre preoperative autologous blood donation programme: the first two years.

OBJECTIVE: To assess the efficacy of a regional autologous blood donation programme. DESIGN: Clinical and laboratory data were collected and stored prospectively. Transfusion data were collected retrospectively from hospital blood bank records. SETTING: Northern Region Blood Transfusion Service and 14 hospitals within the Northern Regional Health Authority. SUBJECTS: 505 patients referred for autologous blood donation before elective surgery. MAIN OUTCOME MEASURES: Patient eligibility, adverse events from donation, autologous blood units provided, and autologous and allogeneic blood units transfused within 10 days of operation. RESULTS: Of 505 patients referred, 354 donated at least one unit. 78 of 151 referred patients who did not donate were excluded at the autologous clinic, mostly because of anaemia or ischaemic heart disease. In 73 cases the patient, general practitioner, or hospital consultant decided against donation. 363 autologous procedures were undertaken. In 213 (59%) cases all requested units were provided. The most common reasons for incomplete provision were late referral or anaemia. Adverse events accompanied 24 of 928 donations (2.6%). Transfusion data were obtained for 357 of the 363 procedures. 281 donors were transfused; autologous blood only was given to 225, autologous and allogeneic blood was given to 52, and allogeneic blood only was given to four. 648 of 902 (72%) units of autologous blood were transfused. Complete provision of requested autologous units was followed by allogeneic transfusion in 12 of 208 procedures (5.8%). Incomplete provision was followed by allogeneic transfusion in 44 of 149 procedures (30%). CONCLUSIONS: This study shows the feasibility of a regional autologous transfusion programme. Autologous donors only infrequently received allogeneic transfusion. Patients should be appropriately selected and referred early.

Blood Banks↗
PubMed1992

Response patterns to central auditory tests and the clinical evaluation of Language Fundamentals--Revised: a pilot study.

Tests of central auditory function and measures of receptive and expressive language abilities were administered to 10 children suspected of having central auditory processing disorders. Eight of the 10 subjects displayed expressive language difficulties, suggesting a need to examine more closely the relationship between expressive language and central auditory processing.

Auditory Perceptual Disorders↗
PubMed1992

Current status of unrelated-donor bone marrow transplantation. The International Marrow Unrelated Search and Transplant (IMUST) Study.

1. The International Marrow Unrelated Search and Transplant (IMUST) Study 1 provides novel prognostic data on outcome of unrelated-donor (UD) searches for patients with well-defined clinical characteristics. Case-types analyzed by multifactorial methods reveal the importance of HLA phenotype, ethnic mismatching, and stage of disease at search request, in predicting search outcome. White patients, with common HLA types and early disease, were least likely to suffer search failure. In contrast, searches for non-White patients with unusual HLA phenotypes and advanced disease were most likely to fail. Of importance, 70% of patients had HLA phenotypes defined as uncommon. 2. Overall donor yield at the 2 UK registries between 1989 and 1991 was 7%, significantly below expectations. Reasons for this shortfall are that theoretical predictions did not consider ethnic mismatch and logistical delays incurred by outdated UD search routines and most importantly HLA-typing inaccuracies. 3. IMUST Study 2 is a prospective multicenter-controlled cohort study comparing HLA-identical sibling donor (ID) and UD-bone marrow transplantation (BMT) for factors affecting BMT outcome. Generous support was provided by 83 BMT centers worldwide. An interim analysis of 165 UD- and 368 ID-BMT, with at least 6 months follow-up after BMT, is described. Unifactorial analysis showed a probability of engraftment at day 100 of 89% after UD- compared with 98% after ID-BMT (p < 0.001). Probability of Grades II-IV acute graft-versus-host disease (AGvHD) at 100 days was 52% after UD- compared with 42% after ID-BMT (p < 0.01). Probability of overall survival at day 400 was 42% after UD- compared with 63% after ID-BMT (p < 0.001). Survival on day 400 of those patients receiving UD-BMT for early disease was encouraging at 52%. 4. Multifactorial analysis was performed on combined data from UD- and ID-BMT cohorts to identify various factors predicting engraftment, AGvHD, and overall survival. Survival after UD-BMT was increased by center experience of UD-BMT and the use of additional pretransplant immunosuppression. Survival was decreased in UD- compared with ID-BMT, by female donor to male recipient and poor-risk disease. Engraftment was improved in ID- compared with UD-BMT, and after UD-BMT at centers experienced in UD-BMT. Engraftment worsened with the use of ex-vivo T-cell depletion for GvHD prophylaxis, in chronic myeloid leukemia, and in male recipients of female marrow.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

HLA-DR and DQ matching by DNA restriction fragment length polymorphism methods and the outcome of mixed lymphocyte reaction tests in unrelated bone marrow donor searches. The IMUST Study.

The use of DNA restriction fragment length polymorphism (DNA-RFLP) typing for HLA-DR and DQ genes was assessed in 96 patients who were HLA-A,B and DR matched by serology with one or more potential unrelated marrow donors (UD). Two hundred recipient-donor pairs from 10 transplant centres in the UK were studied. DNA-RFLP revealed serological errors in HLA-DR typing and identified additional recipient-donor mismatches. Of the 200 allegedly serologically matched pairs, 55 (28%) were mismatched for HLA-DR and/or DQ by DNA-RFLP typing. Of the 200 pairs, 68 (34%) mixed lymphocyte reactions (MLR) were negative and 132 (66%) positive. There was a significant correlation between DNA-RFLP defined mismatch and MLR positivity. However quantitative studies revealed no trend towards increasing MLR relative response index (RRI) with cumulative RFLP defined mismatch (i.e. for DR plus DQ compared with DR or DQ alone). RFLP matching for HLA-DR and DQ failed to predict a negative MLR. The RRI in the graft-versus-host direction was greater in RFLP matched pairs who carried HLA-DR4 than in matched pairs lacking DR4, suggesting that failure of RFLP to characterize DR4 subtypes was one reason why routine prediction of a negative MLR was not possible. Despite these limitations we have shown that DNA-RFLP is a reliable method for HLA-DR, DQ typing in routine UD searches in diverse clinical centres. By reducing the number of UD tested in MLR, RFLP typing can substantially reduce the work involved in donor selection.

Bone Marrow Transplantation↗
PubMed1991

PCR-fingerprinting for selection of HLA matched unrelated marrow donors. Collaborating Centres in the IMUST Study.

HLA typing contributes to the delays that occur in the search for HLA-matched unrelated marrow donors, and that result in poor patient survival. A new DNA technique for testing DR match between patient and unrelated marrow donors has been assessed. The technique is based on the formation of heteroduplexes between heterologous amplified coding and non-coding DNA sequences during the final annealing stage of the polymerase chain reaction (PCR), and different HLA-DR/Dw types give unique banding patterns ("PCR fingerprints") on non-denaturing polyacrylamide gel electrophoresis. HLA-DR matching is by visual comparison of patients' with donors' fingerprints. Identity can be confirmed by mixing donor and recipient DNA before the final stage of the PCR ("DNA crossmatching"). In an assessment of the technique in 53 unrelated HLA-A and HLA-B matched patient-donor pairs, 42 pairs gave the same results with PCR fingerprinting as with DNA-RFLP analysis. In the 11 other pairs DR/Dw mismatches were detected by PCR fingerprinting but not by the standard DNA-RFLP method; PCR-SSO typing with selected sequence-specific oligonucleotides (SSO) confirmed that mismatches were due to different subtypes of DR4. PCR fingerprinting might thus accelerate the selection of unrelated marrow donors by simplifying the logistics of the donor search.

DNA Fingerprinting↗
PubMed1991

Unrelated donor marrow transplantation for severe aplastic anaemia.

Severe aplastic anaemia (SAA) is frequently a lethal disease. Allogeneic marrow transplantation may offer the best chance of a cure but more than 50% of eligible patients will lack a suitable family donor. The development of large volunteer registries has established unrelated donor marrow transplantation (UD-BMT) as a possible alternative in these patients. Early clinical studies indicate that UD-BMT for SAA is associated with a significantly greater risk of graft rejection and graft-versus-host disease (GVHD) than identical sibling BMT. Current strategies for improving results of UD-BMT for SAA include improved patient selection, more precise HLA matching between recipient and unrelated donor, and the use of more intensive pre-BMT immunosuppression and GVHD prophylaxis.

Anemia, Aplastic↗
PubMed1990

Unrelated donor marrow transplantation between 1977 and 1987 at four centers in the United Kingdom.

Retrospectively we analyzed the histocompatibility data and clinical results of bone marrow transplantation in 51 patients who received marrow from unrelated donors (UD) from 1977 to 1987 at one of four UK BMT centers. We compared the results with those obtained in 51 transplants carried out at the same centers using HLA-identical (ID) sibling donors. Of the UD/recipient pairs 32 (63%) were serologically identical for HLA A, B, and DR antigens, and 37% showed varying degrees of mismatch. UD-BMT primary diagnoses were: severe aplastic anemia or Fanconi's anemia (n = 17), acute leukemia (n = 11), chronic myeloid leukemia (n = 21), and other conditions (n = 2). T cell depletion of the graft was associated with a significant improvement in survival in both UD and ID-BMT. Graft failure was more common in recipients of UD than of ID transplants (13 [25%] vs. 5 [10%] P = 0.05) but there was no significant difference in the frequency of acute or chronic graft-versus-host disease. Actuarial survival was superior for recipients of ID transplants (UD vs. ID: 49% vs. 78%, respectively, at 3 months; 32% vs. 63% at one year). Reduced survival for recipients of UD-BMT was confirmed in case control regression analysis (relative risk 3.0, P = 0.01). Nevertheless in patients whose only alternative is a partially mismatched family donor we think that UD-BMT is justified.

Bone Marrow Transplantation↗
PubMed1988

A longitudinal study of serum beta 2-microglobulin levels in haemophilia.

Serum beta 2-microglobulin (beta 2-m) levels were measured in 75 adults with haemophilia A. Beta 2-microglobulin was found to be significantly elevated in haemophiliacs compared with the non-haemophiliac population. There was a greater rise in beta 2-m in HIV antibody-positive haemophiliacs. No further significant increase occurred in the subgroup with HIV-related disease but all these patients had beta 2-m levels greater than or equal to 3 mg/l. Over the study period of 18 months no significant increase in beta 2-m was documented in either HIV antibody-negative or -positive groups. Beta 2-microglobulin was elevated in HIV antibody-negative subjects with raised transaminase levels. No correlation was found between beta 2-m and the amount of factor VIII concentrate infused, T-cell subsets, thrombocytopenia or age. It is concluded that probable reasons for elevated beta 2-m levels in haemophiliacs include infection with HIV and other viruses, chronic liver disease, and repeated antigenic challenge from multiple infusions of factor VIII. The role of serial measurement of beta 2-m in haemophiliacs with a view to predicting the onset of HIV-related disease warrants further study.

Adolescent↗
PubMed1988

Prognostic indicators in centroblastic-centrocytic lymphoma.

The prognostic importance of ploidy and proliferative index (%S + G2) assessed by flow cytometry, mitotic and centroblast counts, and histological growth pattern were evaluated in biopsy specimens taken before treatment from 60 cases of centroblastic-centrocytic non-Hodgkin's lymphoma. Cases with a high proliferative index (greater than or equal to 18%) or DNA aneuploidy showed significantly poorer survival than those with a low proliferative index (less than 18%). A high mitotic count was also associated with a poor prognosis. On multiple regression analysis the flow cytometric assessments and mitotic counts were significant predictors of survival. Assessments of proliferative activity clearly have prognostic potential in centroblastic-centrocytic lymphoma and may permit more accurate characterisation of individual tumours.

Adult↗