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Biomedical subjects

I Cavill

Publications and source records attributed to I Cavill.

At least 37 records · Page 2Linked to original sources

Assessing erythropoiesis and the effect of erythropoietin therapy in renal disease by reticulocyte counting.

Renal disease is characterized by failure of erythropoietin (Epo) production and low bone marrow sensitivity to Epo. The reticulocyte count is the best laboratory marker of erythropoiesis available, but reticulocytes have not been extensively studied in renal disease. Cluster analysis suggests that in non-haemodialysed renal patients the anaemia is associated with uraemia while the reticulocyte number and immature subclasses are correlated with the ineffective erythropoietic component of the anaemia. This emphasizes the importance of treating the renal disease in patients with the anaemia of end-stage renal failure. Human recombinant Epo therapy has been demonstrated to be effective in correcting anaemia in most cases of chronic renal insufficiency. In renal patients the reticulocyte count should only be monitored by automated methods to assure reliability at low counts.

Anemia↗

Iron and erythropoiesis in normal subjects and in pregnancy.

Erythropoiesis is a highly dynamic process which may be monitored by quantitative reticulocyte counting. In chronic renal failure erythropoietin therapy can restore erythropoiesis to normal level. Occult infection and malignancy can limit this response and quantitative reticulocate counting can be used to identify this at an early stage. Iron supply may also be limiting and the measurement of percentage hypochromia is an effective means of detecting this. In pregnancy erythropoiesis is stimulated at a very early stage, direct measurement of red cell mass using a non-radioactive method has shown that half of the increase may occur within the first trimester. Recent studies suggest that erythropoiesis is stimulated very soon after conception.

Erythropoiesis↗

Serum erythropoietin during autologous bone marrow transplantation: relationship to measures of erythroid activity.

Marked elevation of serum erythropoietin (sEPO) occurs following high dose chemotherapy for malignant disease. It has been proposed that the subsequent fall in sEPO constitutes a relative erythropoietin (EPO) deficiency, prompting trials of recombinant EPO to reduce red cell transfusion during chemotherapy. We have investigated these phenomena by serial estimations of reticulocytes and sEPO in 11 autologous marrow transplant recipients. sEPO reached two to five times baseline 0 to 5 days after transplant but the inverse relationship between sEPO and haematocrit was maintained. Observed to expected log sEPO (Epo ratio) rose and fell in parallel with sEPO, remaining greater than 1.0 throughout. A progressive fall in reticulocyte count during chemotherapy was followed by an increase during engraftment. The strong inverse relationships between reticulocytes and Epo ratio in the 10 days after initiating chemotherapy support the hypothesis that loss of EPO-receptor bearing erythroid precursors allows a rise in sEPO during chemotherapy. The elevation of Epo ratio levels during engraftment indicates that it is the availability of EPO-sensitive progenitors, rather than the supply of EPO, that limits the rate of resumption of erythropoiesis after high-dose chemotherapy.

Adult↗

Evaluation of erythropoiesis after bone marrow transplantation: quantitative reticulocyte counting.

Erythroid regeneration is an important and separate element in the engraftment process in allogeneic and autologous bone marrow transplantation (alloBMT, autoBMT). Qualitative visual reticulocyte counting has proved inadequate in the evaluation of erythropoiesis after BMT but automated flow cytometry now allows the reliable quantitation of reticulocytes even to very low levels. Reticulocyte counts and highly fluorescent reticulocyte (HFR) counts (very early reticulocytes) were estimated daily in recipients of 22 autoBMT and 14 alloBMT using a Sysmex R-1000 automated reticulocyte counter. Marrow ablation caused an immediate and rapid fall in both the reticulocyte count and the HFR. Measurable numbers of reticulocytes persisted throughout the hypoplastic period, but HFR fell to zero in the majority of both the autoBMT and alloBMT. HFR rose significantly after a median time of 14 d post-autoBMT, and 12 d post-alloBMT. Attainment of 15 x 10(9)/l reticulocytes and 0.5 x 10(9)/l HFR at day 21 post-transplant was associated with ultimate engraftment in 100% cases. Inadequate engraftment was seen in the majority of patients whose responses fell below these levels. Graft-versus-host disease was associated with a transient slight reduction in reticulocyte count. Neither episodes of infection nor blood transfusions had any significant impact on trends of reticulocytes or HFR. Automated flow cytometric reticulocyte counting has been shown to provide an accessible measure of erythroid activity which may be of predictive value in the management of patients following bone marrow transplantation.

Blood Cell Count↗

Comparison of a modified thiazole orange technique with a fully automated analyser for reticulocyte counting.

Two independent methods for quantitating reticulocyte counts were compared. One used a modified thiazole orange technique and a flow cytometer (Becton Dickinson FACS); the other was a fully automated whole blood analyser (Sysmex R1000). Both methods gave comparable results with a coefficient of variation of less than 5%. Samples measured using the R1000 showed a negligible decrease in the reticulocyte count over five days at room temperature, although there was evidence of continuing intracellular maturation: with thiazole orange there was an apparent increase. A practical reference range of 20-70 x 10(9)/l was established from 89 normal subjects. The close correlation between the two independent estimates indicates the validity of the quantitation of the reticulocyte count and shows that automation allows significant changes within and below the normal range to be detected with a degree of reliability which was not previously possible.

Benzothiazoles↗

Treating renal anaemia with recombinant human erythropoietin: practical guidelines and a clinical algorithm.

Treatment with erythropoietin is highly effective and beneficial if given with care. In view of its cost, however, it is essential to exclude and treat other causes of anaemia before considering using this hormone. After treatment is started the important points for success are regular review of iron availability state combined with a slow correction of the anaemia. Failure of response requires a thorough search for a possible cause, which should be corrected before considering an increased dose of the hormone. Regular monitoring for potential complications, particularly a rise in blood pressure, is required.

Algorithms↗

The treatment of renal anaemia in CAPD patients with recombinant human erythropoietin.

Fifteen severely anaemic patients receiving CAPD were treated with subcutaneous recombinant human erythropoietin (Epo). Ten subjects had a good response with the haemoglobin concentration increasing from less than 8 g/dl to greater than 10 g/dl within 16 weeks. Four patients had a poor response, which was due to infection in two, myelofibrosis in one and unknown cause in another. Epo was ineffective in the remaining individual, probably due to the presence of occult metastatic carcinoma. Iron supplementation in the form of intravenous iron dextran was given to 12 patients when transferrin saturation decreased below 20%. There was a significant increase in red cell volume (P less than 0.005), with a decrease in plasma volume (P less than 0.005). Red cell iron turnover increased (P less than 0.05) but there was no change in red cell lifespan or deformability. Biochemical parameters remained unaltered, as did peritoneal function. Exercise duration improved (P less than 0.001), as did maximal oxygen consumption (P less than 0.01). Four patients required an increased dose of hypotensive drugs. Epo is a safe effective therapy for the anaemia of CAPD subjects.

Adult↗