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Biomedical subjects

S M Lewis

Publications and source records attributed to S M Lewis.

At least 163 records · Page 9Linked to original sources

Myeloid progenitor cells in the circulation of patients with myelofibrosis and other myeloproliferative disorders.

We have measured the numbers of myeloid progenitor cells in the circulation of patients with myelofibrosis (MF) and other myeloproliferative disorders. In general, progenitor cell numbers were increased in the circulation of patients with MF compared with controls. The mean increases were 9-fold for the multilineage progenitor cells (CFU-GEMM), 13-fold for the erythroid progenitor cells (BFU-E), 37-fold for the granulocyte-macrophage progenitor cells (CFU-GM) and 167-fold for the megakaryocyte progenitors (CFU-MK). Splenectomized patients generally had reduced numbers of circulating progenitor cells. In the CFU-MK assay, mature megakaryocytes cultured from patients with MF regularly showed large vacuoles in the nucleus and cytoplasm, unlike control cells. The increased colony formation in patients with MK, involving especially CFU-MK colonies, is consistent with the hypothesis that MF is a primary myeloproliferative disorder in which a megakaryocyte-derived factor predisposes to the formation of marrow fibrosis.

Adult↗

Protocol for evaluation of automated blood cell counters. International Committee for Standardization in Haematology (ICSH).

This protocol is proposed for the evaluation of automated blood cell counters to assess the performance, advantages and limitations of such instruments. It is based on the International Committee for Standardization in Haematology (ICSH) 'Protocol for type testing equipment and apparatus used for haematological analysis' (1978a) and the British Committee for Standardization in Haematology 'Guidelines for the evaluation of instruments used in haematology' (Shinton, England & Kennedy, 1982). The document has been prepared by the ICSH Panel on Cytometry after discussion with colleagues. This tentative protocol will be reviewed 1 year after publication, in accordance with the ICSH rules, before it is adopted as a definitive standard.

Blood Cell Count↗

Factors affecting expired waveform for carbon monoxide.

We previously presented a method based on a computer lung model for determining the distribution of both specific ventilation and specific diffusing capacity. These argon and carbon monoxide (CO) washin and washout studies were obtained in 12 normal subjects and 24 patients with varying degrees of obstructive lung disease. In addition to end-tidal and mixed expired gas concentrations, the expired waveform for both gases was sampled. In patients we found that this method failed to adequately describe CO dynamics during the early part of expiration; predicted concentrations were higher than actual data. Modifications of the original model that satisfy all data are presented. This new model suggests that CO uptake occurs in spaces with ventilatory properties of dead space. The accuracy and reliability of these observations were established by computer simulation studies as well as by repeated testing in one subject. These proved to be highly reproducible over a period of 5 mo. Standard parameter sensitivity tests showed parameters to vary by less than 10% and to be stable even when realistic levels of noise were added to the data. We conclude that studies involving ventilation of insoluble gases are insufficient to describe gas exchange in the lung. The addition of an exchangeable gas adds significant understanding of lung function, particularly in disease.

Adult↗

A simple quantitative estimate of the function of radiolabelled platelets.

The function ex vivo of autologous platelets, labelled with 111In, was evaluated at various times following injection by comparing the retention on foreign surfaces of radioactivity with the retention of total platelets (represented almost entirely by unlabelled and therefore unmanipulated platelets) after the application of fresh un-anticoagulated whole blood to (a) filter paper and (b) glass bead columns. Relative retentions were similar for the two materials, with labelled platelet retention being about 80% that of native platelet retention. Prior to injection, when labelled platelets were returned to an excess of freshly drawn whole blood, retention of radioactivity was greater than that of native platelets with a ratio significantly greater than that seen with labelled platelets tested ex vivo. Filter paper retention provides a simple technique which may be useful for the evaluation of labelled platelet function as a function of platelet age and also, with further standardisation, as an inexpensive rapid test of unlabelled platelet function.

Blood Platelets↗

Failure of medical therapy in tricuspid endocarditis due to Staphylococcus aureus.

A patient with isolated tricuspid endocarditis due to Staphylococcus aureus had persistent bacteremia despite antibiotic therapy for 47 days until surgery. Cultures of the resected valve disclosed 1.4 X 10(8) colony forming units per gram of valve. Time-kill studies done with the strain of S. aureus and the antibiotics used in the therapy of this patient disclosed decreased bactericidal activity of these antibiotics with increasing inocula concentrations. At 10(8) inoculum, only the combination of vancomycin and tobramycin was bactericidal. The inoculum dependence of bactericidal activity might explain the lack of correlation between in vitro susceptibility tests with clinical outcome of some endocarditis patients.

Adult↗

The interpretation of platelet kinetic studies for the identification of sites of abnormal platelet destruction.

The kinetics of platelets labelled with 111In have been studied in a series of 175 subjects including 18 normal volunteers, and 12 patients with idiopathic thrombocytopenic purpura (ITP), but excluding patients in whom there was scintigraphic evidence of intravascular platelet consumption. From analysis of the kinetics, the following parameters were calculated: splenic blood flow (SBF), intrasplenic platelet transit time (t-), splenic platelet pool capacity (expressed as a percentage of the total circulating platelet population), the fraction of the dose of labelled platelets ultimately destroyed in the spleen and the mean platelet life span (MPLS). SBF increased with increasing spleen size up to values of 25% total blood volume (TBV) per min. Some patients with immune complex related diseases were identified with elevated SBF (up to 24% TBV min-1) but without significant splenomegaly. Patients with cardiac decompensation had reduced SBF relative to spleen size. t- showed no relationship with spleen size. It tended to fall in patients who had high SBF relative to spleen size and to rise in those with low SBF relative to spleen size; i.e. it was inversely related to splenic perfusion (flow per unit tissue volume). The splenic platelet pool capacity is dependent on platelet input (SBF) and splenic platelet clearance (reciprocal of t-), and showed a close relationship with spleen size. When all subjects except those with ITP were considered, splenic platelet destruction showed a good correlation (r = 0.70, n = 42, P less than 0.001) with the splenic platelet pooling capacity. The ratio of the fraction of platelets destroyed in the spleen to the fraction pooling there, the D/P ratio, was approximately unity and did not appear to vary with MPLS, spleen size or the patient's condition, except in ITP where it varied between about 0.5 and 2. This variation in ITP was thought to be the result of an immune mediated re-direction of reticulo-endothelial platelet destruction. It is suggested that the D/P ratio, rather than the absolute quantity of 111In labelled platelets destroyed in the spleen, may be a more useful predictor of response to splenectomy since it takes into account the observed, appropriate, tendency for the spleen to destroy platelets in proportion to its platelet pooling capacity.

Blood Flow Velocity↗

Anaemia in myelofibrosis: its value in prognosis.

Forty-four patients with myelofibrosis were investigated in our hospital in the period 1971-81. Their clinical, laboratory and radioisotope parameters were analysed. The direct correlation between plasma volume and splenic red cell pool has highlighted the role of the spleen in the dilutional anaemia seen in myelofibrosis. 52Fe quantitation enabled us to show that the bone marrow contributes relatively more to effective erythropoiesis than the extramedullary sites. The prognostic value of changes in plasma volume and bone marrow 52Fe activity has been demonstrated. We have shown that the Hb: reticulocyte relationship at diagnosis can be used to recognize probable stages of the disease and provides a useful prognostic determinant.

Adult↗

Spurious polycythaemia--a study of 35 patients.

A study of 35 patients with elevated Hb and haematocrit but normal or borderline red cell mass has confirmed that the most common disease association was hypertension and that the peripheral blood findings are reversible when blood pressure is treated, especially when the body haematocrit is low. The situation is probably the result of abnormal distribution of red cells in the circulation. The red cell pool in these patients is normal and they show no evidence of progression to polycythaemia vera. Some cases are associated with smoking and obesity. It is more rational to treat the underlying disease than to attempt to alter the blood volume by venesection.

Diagnostic Errors↗

Evaluation of heat-damaged and IgG-coated red cells for testing reticuloendothelial function.

In vitro methods for standardising and assessing the reproducibility of reticuloendothelial function tests in man were performed. Variation in the degree of heat-induced red blood cell damage could be detected by both Channelyzer plots and a filtration test of red cell plasticity although the former test was less sensitive and difficult to quantitate. In a consecutive study of the clearance of heat-damaged red blood cells (HDRBC) in 8 patients and 2 normal individuals, consistent changes were demonstrated by both assays although occasionally one assay alone provided inconclusive results. When undamaged red cells were coated with IgG anti-D antibodies, the number of IgG molecules bound per red cell was determined by an indirect antiglobulin radioimmunoassay. With this assay, it was shown that the rate of clearance of coated cells was related to the amount of cell bound IgG anti-D. Some variation in the degree of coating of cells from patients with systemic lupus erythematosus was found although the differences were insufficient to account for the reported reduction in the clearance of IgG-coated cells in patients with this disease. The radioimmunoassay and microhaemagglutination techniques revealed that neither IgG, Clq, C3 or C3d were bound to HDRBC following incubation in autologous serum suggesting that these cells were cleared in vivo by mechanisms unrelated to immune receptor recognition.

Antibodies, Anti-Idiotypic↗