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Biomedical subjects

J Stuart

Publications and source records attributed to J Stuart.

At least 127 records · Page 7Linked to original sources

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↗

Rheological importance of acute-phase reactants.

Acute vascular events, and also chronic atherosclerotic vascular disease, are associated with a rise in blood level of several acute-phase reactants. Of these, fibrinogen is of particular rheological importance since hyperfibrinogenaemia causes hyperviscosity of plasma and whole blood and is an adverse prognostic factor in intermittent claudication, coronary artery disease, and stroke. Activation of the monocyte-macrophage system by fibrinogen degradation products, with release of interleukin-1 and secondary stimulation of liver and bone marrow, may be of pathogenic importance in the stress responses of acute and chronic vascular disease.

Acute-Phase Proteins↗

Fluctuating deformability of oxygenated sickle erythrocytes in the asymptomatic state and in painful crisis.

A new gravity filtration technique for the study of sickle cell deformability has shown a significant loss of filterability of oxygenated erythrocytes on day 2 of painful crisis in eight patients with homozygous sickle cell anaemia; there was no increase in irreversibly sickled cell (ISC) count. Serial study (mean of 5.2 occasions) in six out-patients when asymptomatic also showed considerable fluctuation in sickle cell filterability with time; this was again independent of ISC count. Erythrocyte filtration methods demonstrate fluctuations in the rheology of sickle cells that are not detected by ISC counts and which are probably secondary to clinically occult, as well as overt, vaso-occlusive events in the microcirculation.

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↗

Erythrocyte rheology.

Erythrocyte deformability was formerly measured by its contribution to whole blood viscosity. It is now more commonly measured by filtration of erythrocytes through, or aspiration into, pores of 3-5 microns diameter and by the measurement of shear induced erythrocyte elongation using laser diffractometry. Recent improvements in the technology for erythrocyte filtration have included the removal of acute phase reactants from test erythrocyte suspensions, ultrasonic cleaning and reuse of filter membranes, awareness of the importance of mean cell volume as a determinant of flow through 3 microns diameter pores, and the ability to detect subpopulations of less deformable erythrocytes. Measurements of erythrocyte elongation by laser diffractometry, using the Ektacytometer, are also influenced by cell size and need to be corrected for mean cell volume. These advances have greatly improved the sensitivity and specificity of rheological methods for measuring the deformability of erythrocytes and for investigating the mode of action of rheologically active drugs.

Blood Viscosity↗

Kinetic effect of human lactoferrin on the growth of Escherichia coli 0111.

Previous studies have suggested that human lactoferrin has a bacteriostatic effect on Escherichia coli 0111 growth. Determination of the time required for cultures to reach one-half maximal cell density (t1/2) indicates that within the concentration range of lactoferrin used in this study, its effect in vitro on the growth of E. coli 0111 is kinetic rather than bacteriostatic. Compared to a control, added apo-lactoferrin (250-1000 micrograms/ml) produced only a delay effect as seen by an increase in the t1/2 indicating these concentrations are probably within the subinhibitory concentration range. The kinetic delay effect of apo-lactoferrin is also consistently increased in the presence of Zn2+ and Cu2+ cations. Cu2+, Zn2+ and NTA (nitrilotriacetate) did not affect the growth rate of this organism in the absence of lactoferrin compared to the control. These studies indicate that the mechanism by which lactoferrin alters the bacterial growth of E. coli 0111 is more complex than simple iron deprivation.

Cations, Divalent↗

Cell clusters in the nucleus accumbens of the rat, and the mosaic relationship of opiate receptors, acetylcholinesterase and subcortical afferent terminations.

The nucleus accumbens is located ventromedially in the mammalian neostriatum. Nissl- and myelin-stained material from the rat shows that the internal organization of the accumbens features clusters of cells occupying myelin-poor regions. These cell clusters served as basic morphological units against which several other histological features were examined. Markers for opiate receptors, acetylcholinesterase and subcortical afferent termination patterns reveal a mosaic heterogeneity in register with the cell clusters. Specifically, [3H]naloxone binds densely, acetylcholinesterase stains weakly and [3H]amino acids, anterogradely transported from the thalamic paraventricular, paratenial and central medial nuclei and from the ventral tegmental area, label termination-poor zones--all in patterns which correspond to the cell clusters. Details of this fit were provided by Golgi analysis of the spread of cell cluster dendrites. The restriction of dendrites to cell cluster territory, together with the sharply defined edges of opiate receptor and thalamic tract termination patterns, suggests that some connections are excluded from the clusters, and others terminate almost exclusively within their domain. Dopamine fluorescence is weak in the cell cluster areas, supporting the idea that projections from dopaminergic cells in the ventral tegmental area avoid cell clusters. Though certain extrinsic afferent projections are excluded from the cell clusters, it is argued that inputs from nearby striatal enkephalinergic neurons are preferentially received. Taken together, these findings suggest that the cell clusters are way-stations devoted to intrinsic information processing. It is speculated that these concepts can be extended to chemically similar arrangements in the caudate-putamen, which lacks a cytoarchitectural unit as distinct as the cell cluster.

Acetylcholinesterase↗

Blood rheology and proliferative retinopathy in sickle cell-haemoglobin C disease.

Haematological and rheological (plasma and serum viscosity, whole blood viscosity, and erythrocyte filterability) factors were studied in 31 age-sex matched pairs of patients with sickle cell haemoglobin C disease with and without proliferative sickle retinopathy (PSR). Patients with PSR had significantly higher mean cell haemoglobin and lower Hb F levels on average than the matched controls, but the viscosity and erythrocyte filtration indices did not differ between the 2 groups. There was, therefore, no evidence of rheological differences between patients with and without PSR at the time of the study, although transient rheological abnormalities at the time of development of PSR could not be excluded. Prospective longitudinal studies of rheology before, during, and after the development of PSR would be necessary to detect such changes.

Adolescent↗

Endotoxaemia as a cause of fever in immunosuppressed patients.

Using a recently developed chromogenic substrate assay sensitive to 10 pg/ml Escherichia coli endotoxin in plasma, systemic endotoxaemia was found in 52% of 21 episodes of fever in patients with a haematological malignancy who were infected. Endotoxaemia was also found in 27% of 22 episodes of fever of unknown origin. In 45 afebrile patients neither neutropenia nor cytotoxic chemotherapy was a cause of endotoxaemia. Passage of endotoxin from portal blood into the systemic circulation can contribute to unexplained fever in immunosuppressed patients.

Chromogenic Compounds↗

C reactive protein rapid assay techniques for monitoring resolution of infection in immunosuppressed patients.

Three rapid assay techniques (latex agglutination, laser nephelometry, and EMIT enzyme immunoassay) have been evaluated for serial monitoring of the serum C reactive protein (CRP) concentration in immunosuppressed patients with fever. Radial immunodiffusion assay was used as a reference method. Latex agglutination reliably distinguished between normal and raised serum CRP concentrations. Enzyme immunoassay also provided a result within minutes, showed particularly close correlation (r = 0.967) with the reference method, and was free from interference by lipaemic or icteric sera. In 27% of 55 episodes of fever studied serially in immunosuppressed patients, the enzyme immunoassay provided clinically useful information by indicating incomplete resolution of infection despite resolution of fever.

Bacterial Infections↗

Haemorrheological effects of prostaglandin E1 infusion in Raynaud's syndrome.

Eighteen patients with severe Raynaud's syndrome had impaired deformability of erythrocytes, as measured by filtration through 5 micron diameter pores, compared with 19 healthy controls. The patients were given prostaglandin E1 (PGE1) or placebo by intravenous infusion for 72 h to assess the haemorrheological action of PGE1. Contrary to a previous report, PGE1 did not improve erythrocyte filterability. Infusion of PGE1 did, however, evoke an acute phase response with hyperproteinaemia and a leucocytosis and is a potentially important mediator of this stress response in patients with vascular disease.

Adult↗

Anticoagulants and erythrocyte filterability.

Positive-pressure and initial-flow-rate (Hémorhéomètre) filtration systems were used to study the deformability of erythrocytes from whole blood stored in EDTA or heparin. When all contaminating platelets and leucocytes were removed from the erythrocyte suspension there was no significant anticoagulant effect on erythrocyte filtration. Blood may therefore be stored in K2EDTA (1.5 mg/ml blood) or lithium heparin (15 IU/ml blood) for up to 6 hours at room temperature prior to measurement of erythrocyte filterability.

Anticoagulants↗

Leucocyte removal prior to study of erythrocyte deformability.

Positive-pressure and initial-flow-rate (Hémorhéomètre) methods for the study of erythrocyte filtration through 5 micron diameter pores are highly sensitive to the presence of contaminating leucocytes in the erythrocyte test suspension. A pre-filtration step, in which heparinised or EDTA-anticoagulated whole-blood was passed through a column of Imugard IG500 cotton wool, was therefore developed. This procedure removed contaminating platelets and leucocytes, but not erythrocyte sub-populations, and is likely to improve the sensitivity and specificity of erythrocyte filtration techniques.

Cell Separation↗

The acute-phase reaction and haematological stress syndrome in vascular disease.

Both acute and chronic phases of vascular disease are associated with a stress response that includes increased hepatic synthesis of fibrinogen and increased bone marrow release of leucocytes and platelets. A likely humoral mediator of the stress response is interleukin-1 released by reticulo-endothelial cells following their stimulation by fibrinogen degradation fragments D and E. Rheological consequences of the stress response include hyperviscosity of plasma and whole blood and decreased blood filterability. Since blood filterability is influenced by both the plasma fibrinogen concentration and the leucocyte count, it is essential to completely remove these extrinsic contaminants by a pre-filtration step before a true measurement of erythrocyte deformability can be made. Understanding of the pathogenesis of these stress syndromes is also a prerequisite to successful therapeutic control of the rheological abnormality of vascular disease.

Arteriosclerosis↗

Quantitative cytochemistry of blood neutrophils in myelodysplastic syndromes and chronic granulocytic leukaemia.

Quantitative cytochemistry of components of blood neutrophil azurophilic granules (myeloperoxidase, chloroacetate esterase, beta-glucuronidase, and acid phosphatase) and specific granules (lactoferrin) has been performed by scanning and integrating microdensitometry in 13 patients with a myelodysplastic syndrome and 11 patients with chronic granulocytic leukaemia. Both patient groups showed a reduction of enzyme activity in azurophilic granules, and also of lactoferrin, consistent with abnormal development of neutrophil granules. These cytochemical changes in blood neutrophils are similar to those found in acute myeloid leukaemia, are consistent with a leukaemic maturation defect, and may be of diagnostic value.

Acid Phosphatase↗

Quantitative cytochemistry of the toxic granulation blood neutrophil.

A quantitative cytochemical study has been made, using scanning-integrating microdensitometry, of 1000 toxic granulation blood neutrophils from 20 infected patients, in comparison with 1250 normal blood neutrophils. Myeloid precursor cells in 10 normal marrows were also studied. Normal bone marrow granulocyte maturation was associated with a progressive decrease in azurophilic granule enzymes (myeloperoxidase, beta-glucuronidase, acid phosphatase, chloroacetate esterase), and also Alcian blue staining from acid mucosubstance, but an increase in the specific granule marker lactoferrin. Toxic granulation blood neutrophils showed minor changes in the enzyme content of their azurophilic and specific granules, consistent with cell immaturity, and an increase in acid mucosubstance in azurophilic granules. Abnormal maturation of azurophilic granules, with persistence of acid mucosubstance, is the likely explanation for the intense Romanowsky dye staining of the toxic granulation neutrophil.

Acute Disease↗