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Biomedical subjects

T C Pearson

Publications and source records attributed to T C Pearson.

At least 127 records · Page 7Linked to original sources

Venesection in haemoglobin Yakima, a high oxygen affinity haemoglobin.

High oxygen affinity haemoglobins result in polycythaemia and cardiovascular adaptation to maintain tissue oxygenation. The polycythaemia can cause symptoms of hyperviscosity and vaso-occlusive disease. We report a kindred with a high affinity haemoglobin (Haemoglobin Yakima) one of whose members gave birth to two infants with intra-uterine growth retardation and who suffered with symptoms of hyperviscosity which settled on reduction of the PCV by venesection.

Adolescent↗

The haemodynamic responses to venesection and the effects of cardiovascular disease.

The haemodynamic effects of the venesection of one unit (450 ml) of blood over 9 min were measured using non-invasive techniques, in 14 healthy controls and 18 patients with coronary heart disease or hypertension. Venesection was associated with significant reductions in supine and standing systolic and diastolic blood pressure, stroke volume index and cardiac index, and increases in standing heart rate, in both patient groups. No significant differences were observed between the responses of subjects with and without cardiovascular disease. The authors conclude that, in contrast to established teaching, blood loss can be detected in its early stages by careful haemodynamic monitoring and that venesection can be performed safely without volume replacement in patients with stable cardiovascular disease.

Adult↗

Erythropoietin gene expression in haemopoietic cell lines.

Erythropoietin (Epo) gene expression was studied in a number of different haemopoietic cell lines by in situ hybridization and Northern Blot analysis using a radioisotope-labelled monkey Epo DNA probe. A positive message was expressed by a human cell line, CM-S, derived from a patient with congenital hypoplastic anemia, and by a murine erythro-leukaemic cell line, clone 707, derived from the spleen of Friend virus-infected mice. No message was detected in two megakaryoblastic cell lines, and in a monocytic cell line, derived from a patient with acute monocytic leukaemia. These data may fit with the hypothesis of expression of Epo and other growth factors by haemopoietic cells through a mechanism of so-called autocrine secretion.

Animals↗

Apparent polycythaemia.

Patients with apparent polycythaemia are characterised by a raised packed cell volume (PCV; males above 0.51, females above 0.48) but normal red cell mass (RCM; less than 25% greater than predicted). Prediction and interpretation of RCM and PV should be based on height and weight, since the use of body weight alone is misleading. Patients with PCV values up to 0.60 may have apparent polycythaemia but only 18% have a reduced PV (relative polycythaemia). Therefore, the most common cause of the raised PCV is a change in RCM and/or PV within their normal ranges. The clinical associations and possible causes for the RCM/PV changes include male sex, obesity, dehydration, diuretics, smoking, hypertension, alcohol, arterial oxygen desaturation, renal disease and increased catecholamine levels. Retrospective studies of patients with apparent polycythaemia and information from other groups of polycythaemic patients suggest an increased risk of vascular occlusion, although other factors, such as hypertension and smoking, are also involved. Proposed management includes modification of possible underlying causes and examination for risk factors for vascular occlusion. In patients with PCV levels chronically above 0.54 venesection should be used, but patients with PCV values below this level should only be venesected if they are considered to be at risk of vascular occlusion. The suggested target value for PCV for venesected patients is 0.45 or below.

Hematocrit↗

Zinc improves the filterability of sickle erythrocytes at intermediate oxygen partial pressures.

1. The deformability of erythrocytes from patients with sickle-cell anaemia was measured with a St George's blood filtrometer at a range of oxygen partial pressures and at four levels of zinc loading. 2. When incubated in buffered saline containing zinc and the chelator ethyl maltol, erythrocytes rapidly accumulated zinc and thus their oxygen affinity was increased. 3. Neither the oxygen partial pressure nor zinc loading affected the filtration of normal erythrocytes. 4. Deoxygenation of sickle erythrocytes greatly impaired filtration, although the initial filtration rate declined sharply at different oxygen partial pressures (between 70 and 35 mmHg) in different patients. 5. Low levels of zinc (0.03 +/- 0.003 mol of zinc/mol of haemoglobin tetramer) were without effect on sickle cells, but at zinc/haemoglobin ratios of 0.6:1 and above, the sharp fall in filtration rate occurred at oxygen partial pressures 8-25 mmHg below the oxygen partial pressure that impaired filtration of untreated cells. 6. Hence, the deformability of sickle erythrocytes in vitro can be improved by increasing the intracellular content of zinc to 20-fold above normal. Further studies are now required to examine the stability of zinc in erythrocytes, the effects of high intracellular zinc concentrations on erythrocyte viability, and the toxicity of zinc released from zinc-laden cells.

Cells, Cultured↗

Primary thrombocythaemia: diagnosis and management.

Since PT is more likely than reactive thrombocytosis to be complicated by thromboembolic manifestations, the differential diagnosis is important. A combination of positive clinical and laboratory criteria probably represents the most useful diagnostic method at present, although a molecular biological approach may prove to be of value in females in the future. Treatment to suppress the megakaryocytic proliferation is suggested in all patients, since even young patients are not immune to major complications, and treatment may possibly delay long-term myelofibrotic transition. Acute haemorrhage should be treated by platelet transfusions, with or without platelet apheresis and with rapid control of the count by hydroxyurea. Vascular occlusive lesions should be treated with aspirin, with or without platelet apheresis and with hydroxyurea. Busulphan is suggested as the drug of choice for long-term therapy in patients over 40 years of age while hydroxyurea is proposed below this age. The place of interferon-alpha therapy has not yet been established but may have a particular role in women of child-bearing age.

Female↗

Primary thrombocythaemia in pregnancy.

Nine pregnancies in six patients with primary thrombocythaemia are reported. Eight pregnancies resulted in the delivery of normal infants. One pregnancy ended in spontaneous abortion at 7 weeks gestation. One pregnancy was complicated by superficial thrombophlebitis and a postpartum haemorrhage. We suggest that pregnancy in patients with primary thrombocythaemia can have a favourable outcome, but requires close monitoring. Administration of aspirin during pregnancy may be of benefit.

Abortion, Incomplete↗

Red cell lipid peroxidation and antioxidant enzymes in iron deficiency.

Whether iron deficient RBC in humans have a reduced, or an increased, susceptibility to lipid peroxidation was studied in the iron deficiency states of primary proliferative polycythaemia and iron deficiency anaemia and related to changes in the activities of iron-dependent and non-iron dependent antioxidant enzymes. Susceptibility of RBCs to lipid peroxidation was increased when expressed per g Hb. However, this was a result of the low RBC Hb giving an increased membrane lipid: Hb ratio in the incubations. Results were normal when expressed either per cell, or per ml, RBC. Glutathione reductase was normal. Increased RBC superoxide dismutase activity in iron deficiency may be explained by the younger RBC population and reductions in glutathione peroxidase and catalase activities by the microcytic hypochromic changes and the lack of availability of iron, respectively. There is no evidence of an increased susceptibility of RBC to lipid peroxidation in iron deficiency.

Aged↗

Erythropoietin responsive progenitors in anaemia of prematurity.

Circulating erythroid progenitors (BFU-E) in five anaemic preterm infants (haemoglobin less than 100 g/l) were about 2 and 4.4 times as abundant as in 10 preterm infants who were not anaemic and five healthy adults, respectively, and were significantly more responsive to low concentrations of recombinant human erythropoietin (rHuEpo) than those from healthy adults. These results encourage further studies in the use of rHuEpo for the treatment of the anaemia of prematurity.

Adult↗

Sensitivity of erythroid progenitors to recombinant growth factors in the diagnosis of myeloproliferative disorders.

Sixty-six adults were studied with the aim of establishing positive diagnostic criteria for myeloproliferative disease. Erythroid colony formation from peripheral blood progenitors was assayed in a serum-free culture system with the addition of recombinant human growth factors. Endogenous colonies were more frequent in myeloproliferative disease than controls. The mean number of clusters per erythroid burst (BFU-e) in cultures with erythropoietin only was lower in primary proliferative polycythemia (polycythemia vera, PPP) than controls. In PPP, primitive BFU-e demonstrated greater dependence on interleukin 3 than controls, and mature BFU-e more susceptibility to inhibition by alpha-interferon. The findings indicate an abnormal response to several different cellular messengers in PPP, and permit an effective diagnostic discrimination from non-clonal polycythemias.

Adult↗

Primary polycythaemia: positive diagnosis using the differential response of primitive and mature erythroid progenitors to erythropoietin, interleukin 3 and alpha-interferon.

Forty adult subjects were studied with the aim of establishing positive diagnostic criteria in primary proliferative polycythaemia (polycythaemia vera, PPP). These comprised 14 patients with PPP, eight secondary polycythaemia (SP), five idiopathic erythrocytosis, and 13 normal subjects, classified under standard criteria following comprehensive investigation for causes of SP. Erythroid colony formation from peripheral blood in a serum-free system was assayed with the addition of recombinant human erythropoietin (Epo), interleukin 3 (IL3), or alpha-interferon (alpha-IFN). The differential sensitivity of primitive and mature progenitors (BFU-E) was assessed by counting the number of clusters ('sub-colonies') comprising each erythroid burst. 'Endogenous' erythroid colonies were found in both PPP (56%) and controls (17%). In Epo containing cultures, the mean number of clusters per burst was lower in PPP than controls, and the percentage of small (less than or equal to 8 clusters) bursts was higher. In PPP primitive BFU-E demonstrated greater dependence on IL3 than controls, and mature BFU-E greater inhibition by alpha-IFN. These findings suggest an abnormal response to several growth factors, rather than dysfunction of a single growth factor receptor. Regression analysis of these data defined a discriminant of high diagnostic sensitivity and specificity. This discriminant accurately predicted diagnosis in a further nine polycythaemic patients.

Adolescent↗