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Biomedical subjects

J Stuart

Publications and source records attributed to J Stuart.

At least 55 records · Page 3Linked to original sources

Acute abdominal distension following Cryptosporidium infection.

Two children, aged 15 months and 3 years, developed abdominal distension following proven Cryptosporidium enteritis. Both required readmission to hospital and both improved rapidly, one spontaneously and one with the help of an enema. The association of abdominal distension and Cryptosporidium infection has not been described previously.

Abdomen

Induction of siderophore activity in Anabaena spp. and its moderation of copper toxicity.

Growth of Anabaena sp. strain 7120 (in the absence of chelators or added iron) was inhibited by the addition of 2.1 to 6.5 microM copper and was abolished by copper concentration of 10 microM or higher. When the copper was chelated to schizokinen (the siderophore produced by this organism in response to iron starvation), the toxic effects were eliminated. Analysis of culture filtrates showed that the cupric schizokinen remains in the medium, thereby lowering the amount of copper taken up by the cells. Although this organism actively transports ferric schizokinen, it apparently does not recognize the cupric complex. Thus, Anabaena sp. is protected from copper toxicity under conditions in which siderophore is being produced. For cells grown in low iron, the accumulation of extracellular schizokinen was observed to parallel cell growth and continue well into stationary phase. The actual iron status of the organism was monitored by using iron uptake velocity as an assay. Cultures grown on 0.1 microM added iron were found to be severely iron limited upon reaching stationary phase, thus explaining the continued production of schizokinen. These data show that the siderophore system in Anabaena spp. has developed primarily as a response to iron starvation and that additional functions such as alleviation of copper toxicity or allelopathic inhibition of other algal species are merely secondary benefits.

Copper

Oxpentifylline and cetiedil citrate improve deformability of dehydrated sickle cells.

Erythrocytes from 14 patients with homozygous sickle cell anaemia were treated with the calcium ionophore A23187 to induce loss of cellular potassium and water. The dehydrated cells showed a decrease in filterability (loss of deformability) through pores of 5 micron diameter. Oxpentifylline and cetiedil citrate, which preserve erythrocyte cation and water content, had a significant (p less than 0.01) protective effect against loss of deformability at a concentration of 1 mumol/l. Oxpentifylline showed no adverse effect on the rheology, morphology, or haemolysis of sickle cells at concentrations up to 500 mumol/l. Drugs that act on the erythrocyte membrane to maintain cell hydration are of potential rheological benefit in sickle cell anaemia.

Anemia, Sickle Cell

Rheological effects of bed rest in sickle cell disease.

A serial rheological study in two patients with homozygous sickle cell disease whose leg ulcers healed as a consequence of bed rest showed an improvement in erythrocyte deformability (filterability) associated with evidence of decreased haemolysis and a fall in the number of irreversibly sickled cells. This rheological improvement may aid the healing of leg ulcers by increasing blood flow in the ulcer base. The effects of bed rest on the rheology of sickle cell disease should be taken into account in future studies of vaso-occlusive crisis.

Adult

Painful sickle cell crises precipitated by stopping prophylactic exchange transfusions.

A patient with homozygous sickle cell disease showed a reduced incidence of painful crises as a result of regular exchange transfusion, but on three occasions when transfusion treatment was interrupted, a painful crisis occurred. Onset of painful crisis was associated with raised packed cell volume (PCV) or percentage of haemoglobin S (HbS%), or both. Measurement of whole blood viscosity using in vitro mixtures of blood group compatible normal (AA) and sickle (SS) cells showed that above an HbS of 25% any increase in PCV caused a disproportionate increase in whole blood viscosity. These clinical observations and laboratory data suggest that when regular exchange transfusions are terminated both HbS% and PCV should be carefully monitored. Prophylactic venesection should be considered for patients who maintain their PCV after transfusion as HbS% rises.

Adult

Intrinsic factors that influence measurement of erythrocyte deformability.

The efficiency of rheological tests for measuring erythrocyte deformability is a function of test specificity and test sensitivity. Recent improvements in both specificity and sensitivity have revealed that rheological measurements of erythrocyte deformability are affected by the volume, haemoglobin concentration, and shape of the test erythrocytes. This applies both to filtration methods, using pores of 3-5 micron diameter, and to the measurement of erythrocyte elongation by laser diffractometry. Erythrocyte indices and morphology should therefore be measured routinely in both patients and controls so that the values for these intrinsic factors can be correlated with the results of rheological measurements in all published studies.

Blood Viscosity

Ranking of laboratory tests by consensus analysis.

A new analytical technique (consensus analysis) was devised to assess the performance of laboratory tests that are commonly used to monitor the acute and chronic phases of inflammatory disease. On thirty-one tests carried out monthly for 7 months in seventeen patients with rheumatoid arthritis, the consensus analysis procedure ranked plasma viscosity and erythrocyte sedimentation rate in a tie for first place. Measurement of the acute-phase serum protein orosomucoid ranked third. Consensus analysis has the potential to reduce laboratory costs by identifying the most useful tests; it also promises to be helpful in the design of new laboratory tests that are more sensitive and specific.

Adult

Effect of BW12C on oxygen affinity of haemoglobin in sickle-cell disease.

Eight subjects with sickle-cell disease in the symptom-free steady-state received a single one-hour infusion of the new anti-sickling agent BW12C on a total of eleven occasions. A dose-dependent increase in wholeblood oxygen affinity was observed, resulting from the action of BW12C in stabilising the oxy-conformation of haemoglobin and causing a left shift of the oxygen saturation curve. At the highest dose given (20 mg/kg bodyweight), up to 23% of haemoglobin was modified to a BW12C-reacted high-affinity form without evidence of tissue hypoxia. There was biochemical and rheological evidence for a transient decrease in haemolytic rate.

Adult

Blood rheology and proliferative retinopathy in homozygous sickle cell disease.

Some haematological and rheological features were compared in 27 age and sex matched pairs of patients (15 male, 12 female) with homozygous sickle cell (SS) disease with and without proliferative sickle retinopathy (PSR). Significant haematological differences between the groups were a higher haemoglobin and a lower fetal haemoglobin in PSR positive males and a higher MCHC in PSR positive females. The plasma viscosity and characteristics of erythrocyte filterability did not differ between those with and those without PSR, although PSR positive males had a significantly higher whole blood viscosity when measured at high shear and at the patient's own packed cell volume.

Adult

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