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Biomedical subjects

D R Norfolk

Publications and source records attributed to D R Norfolk.

At least 37 records · Page 2Linked to original sources
PubMed1994

The effect of cytokines on the in-vitro erythropoietin bioassay.

The effects of various concentrations of granulocyte macrophage colony stimulating factor (GM-CSF), gamma interferon (gamma IFN) and interleukins 1 alpha (IL-1 alpha), 1 beta (IL-1 beta) and 3 (IL-3) on the anaemic mouse spleen cell bioassay for erythropoietin (EPO) were investigated. Addition of IL-3 and GM-CSF at various concentrations had no effect on EPO stimulated 3H thymidine incorporation. However the addition of IL-1 alpha, IL1-beta and gamma IFN (3.3 x 10(-8) gl-1) caused a significant (P < 0.01) inhibition of EPO stimulated thymidine incorporation. This suggests that the EPO bioassay may be influenced by variable levels of some inflammatory cytokines in serum. Previous studies have shown that the bioassay is influenced by serum transferrin levels and thus serum immunoassays remain the technique of choice for specific estimates of EPO. Since EPO bioassays are not specific, they should be reserved for situations in which an estimate of the total erythropoietic activity of serum is required.

Animals↗
PubMed1994

Persistent clonal expansions of CD3+TCR gamma delta+ and CD3+TCR alpha beta+CD4-CD8- lymphocytes associated with neutropenia.

This communication reports the clinical and cellular features of five elderly female patients with persistent moderate to severe neutropenia and concomitant relative expansions of CD3+TCR gamma delta+ (n = 4) or CD3+TCR alpha beta+CD4-CD8- (n = 1) lymphocyte populations. In clinical terms, severe neutropenia was the main contributing factor to patient symptoms although two additionally had long-standing histories of rheumatoid arthritis. The absolute lymphocyte counts did not exceed the normal upper limit in these patients, and morphologically the lymphocytes were not typically of large granular lymphocyte (LGL) type although LGL-associated BLT-esterase staining was consistently increased. Expression of NK-associated (NKa) membrane determinants (CD16, CD56 and CD57) were variable but there was an apparent correlation between weak membrane CD8 and CD16 expression. DNA genotypic studies confirmed that the four CD3+TCR gamma delta+ cases were clonal in nature and add further support to an emerging impression that expansions of these lymphocyte subpopulations may frequently be clinically associated with autoimmune phenomena in general and neutropenia in particular.

Aged↗
PubMed1993

Circulating intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human malignancies.

Cellular adhesion molecules have been implicated in tumour progression and metastasis. This study examines for the first time the serum concentrations of circulating VCAM-1 and E-selectin in a consecutive series of 110 cancer patients seen in a general medical oncology clinic, and confirms and extends previous studies reporting measurement of circulating ICAM-1. Soluble ICAM-1 and VCAM-1 levels were significantly higher in all the patient groups compared with the controls whereas soluble E-selectin was significantly higher in the ovarian, breast and GI cancer groups and lower in the myeloma group. The significance of these results together with the possible sources and stimuli for release of these adhesion molecules are discussed.

Adult↗
PubMed1993

The relationship of haemoglobin to serum erythropoietin concentrations in the anaemia of rheumatoid arthritis: the effect of oral prednisolone.

Previous studies of the erythropoietin response to anaemia in RA have yielded conflicting findings. Some have found the response to be impaired and others have found a normal response. We have compared erythropoietin (EPO) levels measured by radioimmunoassay, in 54 anaemic rheumatoid patients and 55 patients with iron deficiency anaemia but no inflammatory disease. The erythropoietin response in the rheumatoid patients was impaired compared with the control group (P < 0.025) but only seven rheumatoid patients showed a response which fell below the 95% confidence intervals predicted for the control group. Rheumatoid patients who fell within the highest quartile for serum ferritin concentrations (i.e. those most likely to have anaemia of chronic disease) had significantly lower EPO levels compared with the control group (P < 0.01). EPO levels in rheumatoid patients within the lowest quartile for ferritin (i.e. those with iron deficiency anaemia) were not significantly different from the control group (P = 0.670). The difference in EPO response between the RA patients in the upper and lower quartile for ferritin approached but did not achieve significance (P = 0.056). In a second study 15 anaemic RA patients were given a 5-day course of oral prednisolone 1.5 mgkg-1. Hemoglobin did not rise significantly until day 4 but EPO levels fell by day 1 (P < 0.005) and remained lower than pretreatment values throughout the study. Thus, in RA patients, anaemia of chronic disease is associated with inappropriately low EPO concentrations but this does not appear to be the major cause of the anaemia and Hb response to prednisolone does not depend upon an increase in EPO concentration.

Administration, Oral↗
PubMed1993

A new method to study the efficiency of third generation blood filters.

In order to study the efficiency of third generation blood filters we have devised a new method using 3 microns pore size polycarbonate filter membranes and a filtration chamber to trap leucocytes passing through the blood filter. The method has enabled us to make two important observations: (1) The filters function very efficiently at the start but the efficiency diminishes progressively with time. (2) When the blood flow through the filter is retarded, due to defective priming and/or filter malfunction, the filters fail even at the outset of the transfusion.

Equipment Failure↗
PubMed1992

Anaemia in children following cardiac transplantation: treatment with low dose human recombinant erythropoietin.

Anaemia is common in children following cardiac transplantation. In a series of 5 children with anaemia beyond the immediate post-operative period one had a hypochromic, microcytic anaemia which corrected with oral iron. The other four had normochromic, normocytic anaemias unresponsive to iron or folate supplementation and associated with inappropriately low levels of erythropoietin. Subcutaneous administration of low dose human recombinant erythropoietin to these four patients resulted in correction of their anaemia. Our findings suggest that erythropoietin deficiency is an important cause of anaemia in transplant recipients and should be sought in cases of anaemia refractory to conventional haematinic therapy. In cases of proven erythropoietin deficiency, treatment with erythropoietin is effective, acceptable to patients and preferable to repeated blood transfusion.

Adolescent↗
PubMed1992

A distinct large granular lymphocyte (LGL)/NK-associated (NKa) abnormality characterized by membrane CD4 and CD8 coexpression. The Yorkshire Leukaemia Group.

In a study of 870 individual patients with either lymphocytosis (excluding known lymphoproliferative disease), increased proportions of blood lymphocytes with granular morphology (LGL), or neutropenia, 14 cases were found with abnormally increased CD3+CD4+CD8+ components. Eleven of these were further investigated and 10 shown in follow-up studies to be persistent in nature. Morphological assessments revealed increased LGL in 9/11 cases, and in seven of these > 50% lymphocytes had discernable cytoplasmic granulation. Immunophenotypic studies indicated that CD8 expression by CD4+ lymphocytes in these patients was of low density (CD8dim+), and that both the CD4+CD8- and CD4+CD8dim+ fractions in each patient was characterized by a CD11b+CD16-CD56+CD57+ composite NK-associated (NKa) phenotype (in contrast to normal CD4+CD8- blood lymphocytes and CD4+CD8+ thymocytes which were consistently CD11b-CD16-CD56-CD57-). TCR genotypic studies revealed rearranged components (beta plus gamma, or beta alone) in 5/11 cases, but there were no obvious relationships between TCR configuration (including rearranged band densities) and immunophenotypes, absolute lymphocyte or neutrophil numbers, the proportions of blood LGL, or the proportions of CD4+ cells coexpressing CD8. The occurrence of identical NKa phenotypic profiles in both germline and rearranged TCR cases does, however, suggest the possibility of an evolutionary process from a non-clonal expansion to a clonal state. Serum studies, including soluble CD4, CD8 and IL2-R concentrations and autoantibody investigations, of representative germline and rearranged TCR cases failed to indicate any consistent abnormalities, but there was some suggestion for the existence of a chronic reactive process in some of the patients with germline TCR. These findings suggest that expanded LGL/NKa+ components with phenotypic evidence of CD4/CD8 coexpression should be regarded as a distinct diagnostic category and that persistent CD4+CD8+ abnormalities with germline TCR should be monitored for possible clonal transition.

Antigens, CD↗
PubMed1992

Reduced erythropoietin response to anaemia in elderly patients with normocytic anaemia.

We studied the effect of age on the relationship between haemoglobin and serum erythropoietin (EPO) levels in anaemic patients. 568 patients over 70 years of age were compared with 137 patients under 70 and a reference group of 144 patients of all ages with proven iron deficiency. EPO was measured using a radioimmunoassay. We found that elderly patients with a normocytic anaemia (N = 375) had a statistically lower EPO response than younger patients with normocytic anaemia (N = 61) (p < 0.05) or patients of all ages with iron-deficiency anaemia (p < 0.05). There was no difference between the sexes. Elderly patients with microcytic or macrocytic anaemia had a normal EPO response as compared to the "gold standard" of iron deficiency. These findings suggest that a proportion of elderly patients with normocytic anaemia has an impaired EPO response.

Adolescent↗
PubMed1991

Thalidomide treatment for chronic graft-versus-host disease.

The treatment of chronic graft-versus-host disease (GVHD) may present a difficult therapeutic problem. We used thalidomide to treat six patients with severe chronic GVHD who failed to respond to standard immunosuppressive agents. Four of the six patients showed a clear response to thalidomide, with the fifth patient showing a partial response. The best results were seen in patients with chronic cutaneous GVHD. Two of the patients developed neurophysiological evidence of a peripheral neuropathy, associated with clinical signs in one patient. Measurement of thalidomide plasma levels and pharmacokinetic curves showed a significant inter-patient variation. Peak plasma levels varied from 0.47 to 1.46 micrograms/ml. Thalidomide has a role to play in the management of chronic GVHD and further studies are needed.

Adolescent↗
PubMed1991

Storage and preparation of samples for erythropoietin radioimmunoassay.

The evaluation of a radioimmunoassay for erythropoietin developed using recombinant material as immunogen and radiotracer is presented. A series of serum samples prepared and stored under varying conditions showed that immunoreactive erythropoietin levels were stable at room temperature for at least 10 days and at -20 degrees C for 5 months. The optimum time for separating sera from samples was between 6 and 24 h after venepuncture. Serum EPO values were significantly higher than those measured in heparin or potassium EDTA plasma.

Antibodies↗
PubMed1991

Changes in serum erythropoietin levels during allogeneic bone marrow transplantation.

Serial serum erythropoietin levels were measured in 10 consecutive patients undergoing allogeneic bone marrow transplantation. Observed erythropoietin levels are compared with those predicted from a large control population of anaemic patients not receiving chemotherapy. There was an initial acute rise in serum erythropoietin, peaking between days 1 and 4 after marrow transfusion, which was unrelated to changes in haemoglobin concentration. Patients maintained serum erythropoietin concentrations at around twice the predicted level for the first 2 weeks following transplantation, with a gradual fall into the expected range by wk 3. Erythropoietin levels did not change with episodes of bacterial infection or acute graft-versus-host disease. A patient with severe aplastic anaemia had initial successful engraftment with normalisation of erythropoietin levels, but showed a marked and amplified rise in erythropoietin 2 wk before falling peripheral blood counts indicated failure of the bone marrow graft.

Adolescent↗
PubMed1990

Postoperative autologous transfusion in cardiac surgery. A prospective, randomised study.

To investigate the safety and efficacy of postoperative autologous blood transfusion (AT) using the Shiley hardshell venous reservoir, a prospective, randomised, controlled study was carried out in two matched groups of twenty patients undergoing elective coronary artery bypass surgery. The mean volume of shed mediastinal blood reinfused in the first 6 h postoperatively was 371.7 +/- 63.23 ml. Use of homologous blood was reduced from 760.5 +/- 108.37 ml in the control patients to 466.25 +/- 87.44 ml in the AT patients, a reduction of 38.7% (p less than 0.05). There was no statistically significant difference in the clinical outcome, overall blood loss, use of platelets, fresh frozen plasma and colloids, haematological indices, renal and hepatic functions, or clotting mechanism, although there was a reduction in the fibrinogen level in the patients who received AT (p less than 0.05). Mediastinal blood did not clot and was defibrinogenated. It contained significant levels of haemoglobin (8.175 +/- 0.506 g/dl), platelets (96.55 +/- 10.39 per mm3 10(3)), protein (42.5 +/- 1.13 g/l), calcium (2.385 +/- 0.054 mmol/l) and was well oxygenated (PO2 = 20.46 +/- 0.81 kPa). No patients developed bacteraemia or had any AT-related infections. We conclude that postoperative autologous transfusion using the Shiley hardshell venous reservoir is a safe and efficient method for reducing postoperative homologous blood requirement after coronary artery bypass surgery.

Adult↗
PubMed1990

Erythropoietin deficiency in acute renal failure.

Erythropoietin (Epo) was sequentially measured by radioimmunoassay in 11 patients with acute renal failure (ARF) of varied aetiology. Epo rapidly decreased to a level inappropriately low for the haemoglobin, the reduced Epo value persisting throughout the oliguric phase and for up to 2 weeks after the restoration of apparently normal renal function. Epo values found in ARF were: at referral 18.2 +/- 9.5, mid-oliguria 14.4 +/- 6.8, diuresis 15.6 +/- 5.8, and recovery 25.1 +/- 15.8 mU/ml. Results are compared with 34 patients with end-stage chronic renal failure, 42 with non-renal anaemia, and 96 normal subjects. Epo deficiency alone is an inadequate explanation of the rapid reduction in haemoglobin at the onset of ARF, but would appear to be an important factor in the maintenance of anaemia in prolonged ARF and accounts for the slow increase in haemoglobin following recovery.

Acute Kidney Injury↗