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Biomedical subjects

J Stuart

Publications and source records attributed to J Stuart.

At least 145 records · Page 8Linked to original sources

Preservation of deformability (filterability) of sickle cells by BW12C during progressive deoxygenation.

Venous blood from patients with sickle-cell disease in the steady state or in crisis was progressively deoxygenated in vitro to study the effect of BW12C, a new compound designed to stabilize haemoglobin in the oxy-conformation, on the deformability (filterability) of washed erythrocytes. At a final concentration of 1.5 mM, BW12C significantly increased erythrocyte deformability, compared with no added compound, at all levels of deoxygenation below normal arterial PO2. At concentrations of 3.0 and 5.0 mM, BW12C prevented any significant reduction of erythrocyte deformability, or increase in sickled cells, with deoxygenation down to PO2 values below the normal venous level. These in vitro results demonstrate the considerable potential, as an anti-sickling agent, of this novel compound.

Aldehydes↗

Effect of alpha thalassaemia on the rheology of homozygous sickle cell disease.

A study of rheological determinants (plasma viscosity, whole-blood viscosity, and erythrocyte deformability) was made in 24 matched pairs of patients with homozygous sickle cell disease, with and without homozygous alpha-thalassaemia 2. Patients with coexisting alpha-thalassaemia showed a significant increase in erythrocyte deformability measured as filtration of washed erythrocytes through 5 micron diameter pores and also as viscosity of whole blood at high shear rate (230s-1) and standard haematocrit (0.45). This rheological advantage may explain the beneficial effect of alpha-thalassaemia 2 on haematological parameters and clinical events in homozygous sickle cell disease.

Adolescent↗

Thrombocytosis of active rheumatoid disease.

Two cross-sectional and one longitudinal study of patients with rheumatoid arthritis showed that platelet number correlated with both clinical and laboratory parameters of disease activity, including erythrocyte sedimentation rate, zeta sedimentation ratio, viscosity of plasma and blood, white cell count, liver enzymes, rheumatoid factor, and several acute-phase proteins. There was also an inverse relationship between platelet number and the haemoglobin and serum albumin levels. III Indium-labelled platelet survival was reduced in 4 patients with active rheumatoid arthritis despite a raised platelet count, with labelled platelets being localised to inflamed joints in the 2 patients studied. Platelet aggregation was normal. We suggest that the raised platelet count of active rheumatoid arthritis may be a useful index of disease activity and may represent a bone marrow stress (syndrome) response to shortened platelet survival, with platelet sequestration occurring in areas of synovial inflammation.

Arthritis, Rheumatoid↗

An improved chromogenic substrate endotoxin assay for clinical use.

An improved quantitative assay for endotoxin in plasma was developed after evaluating three different chromogenic substrates and seven methods for removal of plasma inhibitors. Optimal storage conditions for plasma samples prior to assay were also determined. Using chromogenic substrate S2423 with plasma diluted 1/10 in water and heated to 75 degrees C for 5 min to remove inhibitors, a within-batch coefficient of variation of 4% was obtained at levels of endotoxin likely to be encountered clinically. The limit of assay sensitivity was less than 10 pg/ml. This assay provides a sensitive quantitative test for single episodes of endotoxaemia in individual patients but variable activation of the Limulus proenzyme by endotoxin from different bacterial strains limits quantitative comparisons between patients.

Blood Preservation↗

Amoebic meningitis also occurs in NSW.

The clinical, pathological and laboratory findings of a 3-year-old boy with proven primary amoebic meningo-encephalitis are described. The EEG showed changes of acute cortical necrosis lateralised to one temporal lobe and was similar to that described with Herpes simplex encephalitis. CT scan findings indicated acute cortical inflammation and basal arachnoiditis. The disease should be suspected in the context of acute pyogenic meningitis when no organisms are isolated. Treatment with amphotericin-B, miconazole and rifampicin has been effective in previously reported patients.

Amebiasis↗

Haemophilia and the kidney: assessment after 11-year follow-up.

Radiological and biochemical investigations of renal function were performed in 57 patients with haemophilia, 27 of whom had been previously investigated in 1969. Although one-third of patients had a renal radiographic abnormality, only two had abnormalities persisting since 1969 and attributable to renal bleeding. Isotope renography was a sensitive indicator of renal abnormality whereas a history of haematuria was a poor discriminator for patients with abnormal intravenous urograms or impaired creatinine clearance. Haematuria was not associated with progressive loss of renal function and its natural history in haemophilia is probably benign.

Adolescent↗

Haemostatic and rheological changes in normal pregnancy and pre-eclampsia.

Platelet activity (microaggregate formation, ADP-aggregation and beta-thromboglobulin release), coagulation activity (fibrinogen level and factor VIII related antigen/coagulant activity), and rheological factors (plasma viscosity, whole-blood viscosity and erythrocyte deformability) were studied serially in 14 healthy pregnancies to determine the effect of gestational age. Fourteen patients with pre-eclampsia, each matched for stage of gestation with a normal pregnancy, showed normal rheology of circulating blood and normal aggregability of circulating platelets, but there was a significant increase in platelet release of beta-thromboglobulin and a shorter platelet production time, indicating a shorter life-span. The results suggest that localized platelet activation within the utero-placental microvasculature, rather than a rheological abnormality, is a likely contributory factor to the occlusive vascular lesion of pre-eclampsia and fetal growth retardation.

Adolescent↗

Serum levels of acute phase and cardiac proteins after myocardial infarction, surgery, and infection.

C-reactive protein and four other acute phase reactant proteins of non-cardiac, origin (orosomucoid, alpha 1- antitrypsin, heptoglobin, and alpha 2- macroglobulin) were studied serially by laser immunonephelometric assay in sera from 17 patients with myocardial infarction. A similar comparison was made in 57 patients undergoing surgery and 72 patients with acute infection. C-reactive protein was consistently the most sensitive acute phase reactant in all three conditions. After myocardial infarction, a raised serum C-reactive protein level was found on admission in four patients before a rise in creatine kinase MB isoenzyme (CK MB). The peak C-reactive protein level was reached on the third post-infarct day and it then declined over seven days with a half-life similar to myocardial tropomyosin. Serial monitoring of serum C-reactive protein, in parallel with cardiac proteins of short half-life (CK MB) and long half-life (tropomyosin), provides maximal information for diagnosis and for detecting post-infarct complications.

Alpha-Globulins↗

Platelet inhibition with Ticlopidine in atherosclerotic intermittent claudication.

Fifty-one men with atherosclerotic intermittent claudication and haemorheological abnormalities completed a double-blind, one-year randomised trial of Ticlopidine (500 mg/day), a new antiplatelet agent. Ticlopidine caused significant inhibition of platelet aggregation but did not fully correct abnormalities of coagulation, viscosity, and fibrinolysis. There was no significant improvement in walking ability, Doppler ankle-pressure indices, or calf blood flow. Sustained platelet inhibition for 12 months was insufficient to correct the prothrombotic abnormality of extensive atherosclerosis.

Adult↗

C-reactive protein concentration as a guide to antibiotic therapy in acute leukaemia.

Serial monitoring of the serum C-reactive protein (CRP) concentration was performed, using a one-hour laser-immunonephelometric assay, during 29 episodes of infection in 22 neutropenic patients with acute leukaemia. Serum CRP increased to above a diagnostic level of 100 mg/l in all 29 episodes and continued to rise progressively until appropriate antibiotics, or granulocytes, were given when it fell with a half-life of approximately three days. Serial study of the serum concentration was of value in detecting occult or unresolved bacterial infection and provided an objective means of monitoring the response to antibiotic and granulocyte therapy.

Acute Disease↗

To tell or not to tell: haemophiliacs' views on their employment prospects.

As part of a study on the employment situation of haemophiliacs carried out by four Haemophilia Centres in the United Kingdom, the patients were invited to express their own views on their employment problems and prospects. 225 patients, most of them severely or moderately affected by the disease, made comments which were classified into eight categories. The results show that one third of the patients were preoccupied with whether or not to tell the employer about their condition. The ignorance of employers about haemophilia and of the benefits of self-treatment was also emphasised by many patients. It appears that education of both potential employers and of the public is essential for the rehabilitation of, and the provision of, satisfactory working conditions for the haemophiliac.

Adolescent↗

Erythrocyte deformability in sickle-cell crisis.

A serial study of erythrocyte deformability, plasma viscosity, and whole-blood viscosity has been made during 10 sickle-cell vaso-occlusive crises. The peak serum lactate dehydrogenase level was used to confirm the duration of crisis and the rheological changes were compared with 19 estimations made on the same patients when asymptomatic. Erythrocyte deformability, measured by filtration of washed erythrocytes through polycarbonate filters of 5 microgram pore size, was significantly reduced on day 1 of crisis and, in one additional patient, this occurred 24 h before the onset of pain. There was no increase in irreversibly-sick-led-cell counts and plasma- and blood-viscosity did not increase significantly until day 5 of crisis, in parallel with the acute-phase rise in plasma fibrinogen. Measurement of erythrocyte filterability is therefore a valuable technique for investigating the pathogenesis of the early stages of sickle-cell crisis.

Adolescent↗

Serial study of C-reactive protein during infection in leukaemia.

Serum C-reactive protein was studied serially by a 1-hour laser nephelometric assay in 25 patients with leukaemia who developed 34 episodes of infection. The serum level rose above, or by, 100mg/l in 29 of the episodes. Serial measurement of this acute-phase reactant was of value in detecting infection in the neutropenic patient and in monitoring the response to antibiotic therapy.

Bacterial Infections↗

Haematological stress syndrome in atherosclerosis.

Forty patients with atherosclerotic peripheral vascular disease, as compared to 29 healthy controls, showed a significant increase in platelet number and activity, a neutrophil leucocytosis, and a raised level of several acute-phase reactant proteins (fibrinogen, antithrombin III, factor VIII, and serum globulin). The hyperproteinaemia was associated with increases in plasma-, serum-, and blood-viscosity and is the likely cause of the hyperviscosity of vascular disease. These multiple haemostatic abnormalities closely resemble the non-specific, haematological stress-syndrome response to acute and chronic inflammatory disorders. In atherosclerosis also they may represent a non-specific, secondary response and neither be of aetiological significance nor reflect continuing low-grade intravascular coagulation.

Aged↗

Efficiency of haematological screening tests for detecting disease.

A new "intermediate' reference (normal) range for the erythrocyte sedimentation rate has been compared with published "low' and "high' reference ranges in a study of 354 hospital patients. The "intermediate' range showed superior balance between sensitivity and specificity in the detection of disease-induced plasma protein abnormalities and and gave a test efficiency of 81.9%; this reference range can therefore be recommended for routine use in the diagnostic laboratory. Four other screening tests (whole-blood viscosity, plasma viscosity, zeta sedimentation ratio, and C-reactive protein level) were compared in the same 354 patients. Whole-blood viscosity proved to be unsuitable as a screening test (efficiency 44.8%) but the three other tests showed good balance between sensitivity and specificity and gave a test efficiency of 74.4-79.7%.

Blood Protein Disorders↗

Hyperviscosity and thrombotic changes in idiopathic and secondary Raynaud's syndrome.

Whole-blood viscosity (measured at 128, 23 and 0.2 s-(1) was significantly increased in 29 females with Raynaud's syndrome, 13 males with vibration-induced Raynaud's syndrome, and 18 males with calf claudication secondary to atherosclerosis, as compared with 50 healthy controls matched for sex, age and smoking habit. Viscosity was higher at low temperature (27 and 22 degrees C) in all three types of vascular disease and, despite symptoms of cold hypersensitivity, patients with Raynaud's syndrome did not show selective hypersensitivity at low temperature. Patients with vascular disease, irrespective of aetiology, also showed an increase in the acute-phase reactants haptoglobin, fibrinogen, and factor VIII antigen, together with reduced fibrinolytic activity and minor activation of platelets. These alterations in viscosity and haemostatic factors in vascular disease are probably related to the degree, rather than the aetiology, of endothelial damage and their cumulative effect may contribute to local stasis and thrombosis, particularly in cold extremities.

Adult↗

Blood rheology.

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Anticoagulants↗