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Biomedical subjects

D Bareford

Publications and source records attributed to D Bareford.

At least 19 recordsLinked to original sources

Continuous intravenous infusion of high-dose recombinant interleukin-2 for acute myeloid leukaemia--a phase II study.

A group of 13 patients with acute myeloid leukaemia of differing disease status were treated with continuous intravenous infusion of high-dose recombinant interleukin-2 (rIL-2). There was up-regulation of the cellular cytotoxic functions in all these patients following the rIL-2 therapy, with increase in the natural killer (NK) activity, lectin-dependent cellular cytotoxicity, induction of cytotoxicity-linked cytoplasmic serine esterase and lymphocyte activation. However, the clinical response to rIL-2 in these patients was disappointing, especially in patients treated in frank relapse. Although 1 patient treated in early second relapse achieved a third complete remission, the duration of the remission was brief and lasted only 6 months. Adverse reactions among these patients were common. Whether or not lymphokine-activated killer cells are needed to improve the response rate over rIL-2 alone in these patients deserves further investigation.

Adult

A comparative study of imipenem versus piperacillin plus gentamicin in the initial management of febrile neutropenic patients with haematological malignancies.

Three-hundred and twelve episodes of fever in 234 neutropenic patients with haematological malignancies were treated empirically with either imipenem or a combination of piperacillin and gentamicin. There were no significant differences in the percentages of patients responding to therapy at either 72 h (59% and 56% of assessable episodes in the imipenem and combination groups respectively) or at the end of treatment (55% and 53% of assessable episodes in the imipenem and combination groups respectively). Patients in the piperacillin plus gentamicin group experienced significantly more renal tubular damage whereas those who received imipenem suffered more nausea or vomiting. We conclude that imipenem monotherapy represents an acceptable alternative to piperacillin plus gentamicin as empirical therapy of the febrile neutropenic patient.

Adolescent

The effect of antihypertensive drugs on in vivo platelet activity in essential hypertension.

OBJECTIVE: To investigate whether antihypertensive drugs have a beneficial effect upon the abnormal in vivo platelet function found in patients with essential hypertension. DESIGN: A cross-sectional study in which plasma beta-thromboglobulin, a marker of in vivo platelet activation, was measured in patients with essential hypertension on various antihypertensive drugs. All were free from any other diseases which might affect platelet function. METHODS: Plasma beta-thromboglobulin was measured in 24 patients with untreated essential hypertension, 21 normotensive control patients, 16 patients receiving angiotensin converting enzyme (ACE) inhibitors, 16 patients receiving a beta-adrenoceptor blocker, 12 patients receiving calcium antagonists and 12 patients receiving a diuretic alone. RESULTS: Untreated hypertensives had significantly elevated plasma beta-thromboglobulin levels compared with controls. Plasma beta-thromboglobulin levels in patients receiving beta-blockers and diuretics were not significantly different from untreated hypertensives. Treatment with calcium antagonists was associated with lower plasma beta-thromboglobulin levels, but this difference was not statistically significant. In contrast, treatment with ACE inhibitors was associated with significantly lower plasma beta-thromboglobulin levels compared with untreated hypertensives. CONCLUSION: These results suggest that antihypertensive drugs have different effects upon abnormal in vivo platelet function in patients with essential hypertension. The apparent beneficial effect of ACE inhibitors may mean that they have more impact than other drug groups in the prevention of coronary heart disease.

Adrenergic beta-Antagonists

Inappropriate use of laboratory services: long term combined approach to modify request patterns.

OBJECTIVE: To see whether changes in request patterns for haematological tests could be influenced in the long term by information released from a haematology department. DESIGN: Analysis of request patterns by hospital divisions before and after intervention and of costs of intervention and savings achieved. SETTING: Haematology laboratory of an inner city district general hospital. INTERVENTIONS: Monthly release of a comparison of clinicians' workload statistics, issue of on call guidelines, and promulgation of information (by seminars and factsheets) on appropriate use of tests. MAIN OUTCOME MEASURES: Request patterns before and after intervention. RESULTS: During the year after intervention requests fell by at least a fifth, and the reduction persisted over the next two years. The reduction was most pronounced in relation to inpatients within the division of medicine, for whom requests fell from an average of 4.0 per patient in the six months before intervention to 2.9 per patient in the six months after. CONCLUSIONS: A definite and sustained reduction in inappropriate requests for laboratory investigations may be achieved by an ongoing policy of intervention including issuing guidelines and factsheets and holding seminars, but a positive attitude among senior consultant staff is crucial.

Costs and Cost Analysis

Post-transfusion thrombocytopenia: its duration in splenic and asplenic individuals.

Previous work in our department showed that after blood transfusion, the platelet count often falls to levels which are clinically significant. The probable site of platelet sequestration was identified as the spleen, and post-transfusion thrombocytopenia was prevented by blood filters which remove microaggregate debris from the donor blood. Since the duration of the thrombocytopenia has not been investigated, the purpose of the present study was to establish the rate of onset and duration of post-transfusion thrombocytopenia following packed red blood cell transfusions. In addition, the effect of spleen size, patients' diagnosis and post-transfusion history were examined. These observations provide interesting new data on the mechanisms involved in this phenomenon.

Humans

Thrombocytopenia following routine blood transfusion: micro-aggregate blood filters prevent worsening thrombocytopenia in patients with low platelet counts.

11 patients with anaemia and thrombocytopenia due to bone marrow failure each received 2 sets of red-cell transfusions. They were randomised to receive 1 blood transfusion through a standard 170-micron giving set filter and another through a 40 micron micro-aggregate filter. After transfusion, the mean fall in platelet count was 15 x 10(9)/l (41.7%) and 1.4 x 10(9)/l (4.6%), respectively (p less than 0.01). The results confirm the findings of a previous study which showed that micro-aggregate filters prevent a post-transfusional decrease in platelet counts. In addition, this new study shows that this is clinically relevant in patients who are thrombocytopenic at the time of their blood transfusion.

Anemia

Laboratory tests for monitoring prophylactic exchange transfusion in pregnancy complicated by sickle cell disease.

Prophylactic exchange transfusion is of uncertain value in pregnancy complicated by sickle cell disease (SCD), and there is a lack of laboratory tests to monitor its effect and determine the optimal number and frequency of transfusions. In a prospective study of four consecutive pregnancies complicated by SCD, the product of the PCV and percentage of haemoglobin S gave a 'sicklecrit' value that showed a significant (P less than 0.01) improvement following transfusion. Erythrocyte filterability through pores of 5 microns diameter also improved significantly (P less than 0.05) whereas whole blood viscosity did not, owing to the overriding effect of the increase in PCV. Measurement of sicklecrit and erythrocyte filterability, reflecting blood rheology in large and small vessels respectively, may therefore be used to monitor the effects of exchange transfusion in SCD.

Anemia, Sickle Cell

Splenic platelet-sequestration following routine blood transfusion is reduced by filtered/washed blood products.

The mean fall in the platelet count following 23 routine transfusions of 3-5 units packed cells for anaemia was 32.5%. This was significantly reduced to 12.5% in 15 similar transfusions through a 40 microns microaggregate filter (P less than 0.01) and to 4.6% following five transfusions through a polyester fibre filter (P less than 0.005). In 10 transfusions with frozen or polyester fibre filtered, washed red cells, the decrease in platelet count was 4.2% (P less than 0.001). A study of 111In-oxine labelled autologous platelets in nine patients indicated that the fall in platelet count was due to increased splenic sequestration. Since thrombocytopenia following routine transfusion is reduced by procedures which filter the packed cells, the decrease in platelets is probably caused by their adherence to infused microaggregate debris causing their premature removal from the circulation. Patients with preexisting thrombocytopenia who receive red cell transfusions for anaemia, should therefore receive blood products depleted of microaggregate debris in order to avoid exacerbation of thrombocytopenia and haemorrhagic complications.

Anemia

Effects of hyperglycaemia and sorbitol accumulation on erythrocyte deformability in diabetes mellitus.

Erythrocyte deformability was studied in a total of 83 poorly controlled diabetics (mean blood glucose 12.2 mmol/l) who were divided into three groups, each with matched healthy controls. There was no appreciable difference between diabetics and matched controls regarding the filtration of erythrocytes through 3 micron diameter straight channel pores (25 diabetics) or tortuous channel pores (28 diabetics), or for the measurement of erythrocyte elongation over a range of osmolalities in the Ektacytometer (30 diabetics). When erythrocytes from 17 additional diabetics and 17 healthy controls were incubated for two hours at 37 degrees C in hyperglycaemic (50 mmol glucose/l) buffer, however, there was a considerable reduction in erythrocyte filterability for both diabetics and controls in parallel with an increase in erythrocyte sorbitol concentration. This loss of filterability was prevented by the addition of an aldose reductase inhibitor (Sorbinil). High glucose concentrations (congruent to 50 mmol/l) impair the filterability of erythrocytes through 3 micron pores, and the intracellular accumulation of sorbitol in poorly controlled outpatients is therefore unlikely to have a major adverse effect on erythrocyte rheology in diabetes mellitus.

Adult

Speed of relapse in children with acute lymphoblastic leukaemia.

16 children with acute lymphoblastic leukaemia (ALL) who relapsed on maintenance treatment between September 1978 and December 1981 were studied. Their previous bone marrow aspirates were reviewed to determine the first evidence for marrow relapse and the subsequent rate of evolution of the disease. 60% of children had bone marrow evidence of unsuspected relapse at 8 wk, and 40% had evidence at 12 wk before clinical or peripheral blood relapse occurred. Early detection of relapse will prevent continued use of ineffective maintenance chemotherapy and may also reduce morbidity during subsequent induction therapy. Regular 8-weekly marrow aspirates are therefore recommended during first remission of ALL in children with a histocompatible sibling who would be eligible for bone marrow transplantation in second remission.

Bone Marrow Examination

Follow-up of normal individuals with a positive antiglobulin test.

Over a period of 20 yr (1962-1982), 67 apparently fit donors at a Regional Blood Transfusion Service were found to have an unexplained positive direct antiglobulin test (DAT). During 1983, 26 were traced and re-tested. 9 still had a positive DAT only 1 of whom had developed autoimmune haemolytic anaemia. 17 had become negative though in 7 of these an autoantibody could still be detected by an enzyme technique. Unlike patients with established autoimmune disorders, the positive DAT individuals were found to have normal T cell subsets though B cells were significantly increased.

Adult

Erythrocyte deformability in peripheral occlusive arterial disease.

A rheological study of 32 patients with peripheral occlusive arterial disease (POAD), compared with 32 matched healthy controls, has shown no loss of erythrocyte deformability as measured by filtration methods (using initial flow rate and positive pressure instruments, polycarbonate and silver membranes, and 3 microns and 5 microns diameter pores) or by viscometry (using laser visco-diffractometric and high shear rate viscosity methods). Erythrocyte ATP concentration in POAD was also normal. Patients with POAD showed a small (4 fl) increase in mean erythrocyte volume, associated with a raised serum gamma-glutamyl transpeptidase concentration, which correlated with erythrocyte filtration and viscometric measurements. Previous reports of impaired blood filterability in POAD probably reflect the effects of accompanying leucocytosis, plasma hyperfibrinogenaemia, or an increase in erythrocyte size, but not an intrinsic loss of erythrocyte deformability.

Adenosine Triphosphate