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Biomedical subjects

J Dawes

Publications and source records attributed to J Dawes.

At least 55 records · Page 3Linked to original sources
PubMed1990

Inflammatory response, neutrophil activation, and free radical production after acute myocardial infarction: effect of thrombolytic treatment.

Activated neutrophils releasing proteolytic enzymes and oxygen free radicals have been implicated in extending myocardial injury after myocardial infarction. Neutrophil elastase was used as a marker of neutrophil activation and the non-peroxide diene conjugate of linoleic acid was used as an indicator of free radical activity in 32 patients after acute myocardial infarction; 17 were treated by intravenous thrombolysis. Patients with acute myocardial infarction had higher plasma concentrations of neutrophil elastase and the non-peroxide diene conjugated isomer of linoleic acid than normal volunteers or patients with stable ischaemic heart disease. Patients treated by thrombolysis had an early peak of neutrophil elastase at eight hours while those who had not been treated by thrombolysis showed a later peak 40 hours after infarction. The plasma concentration of non-peroxide conjugated diene of linoleic acid was highest 16 hours after the infarction irrespective of treatment by thrombolysis. Quantitative imaging with single photon emission tomography showed decreased uptake of indium-111 labelled neutrophils in the infarcted myocardium (as judged from technetium-99m pyrophosphate) in those who had received thrombolysis, suggesting a decreased inflammatory response. The results indicate increased neutrophil activation and free radical production after myocardial infarction; they also suggest that thrombolysis does not amplify the inflammatory response and may indeed suppress it.

Adult↗
PubMed1990

Comparison of the pharmacokinetics of enoxaparin (Clexane) and unfractionated heparin.

The pharmacokinetics of enoxaparin (Clexane) and unfractionated heparin were compared by crossover study in healthy volunteers, using three different assays. After intravenous administration, unfractionated heparin was cleared with a half-life of 35 min, irrespective of assay methods. However, the concentration of enoxaparin, measured by competitive binding assay, declined with the longer half-life of 60 min, and its anti-Factor IIa and anti-Factor Xa activities had half-lives of 40 and 275 min, respectively. These data may reflect more rapid clearance of longer chain molecules with anti-Factor IIa activity, or release by enoxaparin of an endogenous compound with anti-Factor Xa activity. Following subcutaneous injection, the bioavailability of enoxaparin was 3-fold greater than that of unfractionated heparin; unlike unfractionated heparin, enoxaparin was almost completely absorbed. Peak plasma concentrations occurred 3 h after injection. The pharmacokinetic parameters of enoxaparin were not affected by dose; by contrast, the half-life of unfractionated heparin was highly dose-dependent. The pharmacokinetics of both unfractionated heparin and enoxaparin did not display circadian variation, and neither preparation crossed the human placenta.

Heparin↗
PubMed1989

The absorption, clearance and metabolic fate of dermatan sulphate administered to man--studies using a radioiodinated derivative.

An iodinated derivative of dermatan sulphate was administered by the intravenous, subcutaneous and oral routes to healthy human volunteers in conjunction with unlabelled dermatan sulphate. Following intravenous injection clearance of radiolabel and concentration as measured by competitive binding assay were highly correlated and displayed complex kinetics which were not dose-dependent. Intact 125I-dermatan sulphate was absorbed following both subcutaneous and oral administration, though there appeared to be selective uptake by the gut of a subfraction comprising the smaller or less sulphated molecules. The intact material was subsequently excreted unchanged in the urine. Degradation products of dermatan sulphate were not detected by either gel filtration or affinity chromatography on Polybrene-Sepharose at any time in either plasma or urine, indicating that administered dermatan sulphate is not catabolised by man.

Absorption↗
PubMed1989

Thrombospondin in malignant and non-malignant breast tissue.

Cytosols of malignant breast tissue contained significantly higher levels of thrombospondin (TSP) and von Willebrand factor (vWF) than non-malignant breast. TSP and vWF content of human breast were significantly correlated whereas there was no correlation between TSP and the platelet-specific protein beta-thromboglobulin (beta TG). Whilst TSP in pre-menopausal breast cancer was slightly lower than in post-menopausal breast cancer, it did not correlate with oestrogen receptors (ER) or progesterone receptors (PR), but was negatively correlated with tissue-type plasminogen activator (tPA), an oestradiol-inducible enzyme. Secretion of TSP by MCF-7 cells was low and refractory to hormones. High levels of TSP appeared to be associated with the centre of the tumour mass. It is suggested that activation of the endothelium may be responsible, at least in part, for the high levels of TSP found in malignant breast tissue and could be a factor in the growth and spread of breast cancer.

Breast↗
PubMed1989

Neutrophil activation during cell separation procedures.

Leucocytes labelled with 111In or 99Tcm are used as diagnostic agents for detecting sites of infection by scintigraphy. Before radiolabelling is performed, leucocytes are isolated from whole blood. The effect of isolation procedures on neutrophil activation has been studied by measuring the neutrophil elastase produced during incubation of whole blood with three erythrocyte sedimentation agents (dextran 70, hydroxyethyl starch and methylcellulose) and two density gradient media (Percoll and Mono-Poly Resolving Medium). Neutrophil elastase was measured using a standard radioimmunoassay. At 21 degrees C, dextran caused no elastase release while hydroxyethyl starch and methylcellulose induced significant release (p = 0.01 and p less than 0.01 resp.). All three agents caused significant elastase release at 37 degrees C. When whole blood was incubated with Percoll and Mono-Poly Resolving Medium, no release of neutrophil elastase was observed. These results show that neither density gradient medium induces neutrophil activation but that certain erythrocyte sedimentation agents do. Of the three sedimentation agents investigated, dextran is the agent of choice if neutrophil activation is to be minimized.

Cell Separation↗
PubMed1989

Safety and pharmacokinetics of the low molecular weight heparinoid Org 10172 administered to healthy elderly volunteers.

1. In a cross-over study a new low molecular weight heparinoid Org 10172 was administered to 12 elderly male and female volunteers. It was well tolerated and no adverse effects occurred. 2. The absolute bioavailability of Org 10172 as measured by plasma anti-Xa activity, glycosaminoglycuronans with no affinity to antithrombin III (NoA-GAG) and thrombin generation inhibiting activity approached 100% in both sexes. 3. The half-life of elimination of its anti-Xa activity (19.2 +/- 6.1 h) was similar to that found previously in young volunteers. Org 10172 was further characterised by a rapid disappearance from the circulation of its anti-thrombin activity (t1/2 1.8 +/- 0.6 h) and of the NoA-GAG (t1/2 3.5 +/- 2.1 h). 4. Its thrombin generation inhibiting activity was of intermediate duration (t1/2 elimination 6.2 +/- 4.0 h).

Administration, Cutaneous↗
PubMed1989

Coagulation disorder due to apparent inadvertent heparin administration.

A new competitive binding assay, which measures the concentration of heparin rather than its activity, was used to confirm the presence of a high concentration of heparin in blood samples from a patient which showed unexpected gross prolongation of thrombin time (TT) and activated partial thromboplastin time (APTT). Extrapolation of the heparin concentration enabled estimation of the likely time of administration and the probable dose given. It is possible that an error in dosage may have arisen due to the striking resemblance of vials containing different amounts of heparin marketed by different manufacturers. There is a need for the adoption by manufacturers of a standard coding scheme for vials containing different amounts of heparin (as is adhered to in the case of some drugs, e.g. warfarin), in order to pre-empt this possible source of error.

Adult↗
PubMed1989

Neutrophil activation in pregnancy-induced hypertension.

Human neutrophil elastase may be a major mediator of vascular damage and could contribute to the vascular damage seen in women with pregnancy-induced hypertension (PIH). Elevated plasma levels of this substance will reflect neutrophil activation in vivo. To determine neutrophil activation in PIH, we studied 30 normal non-pregnant women, 32 women with normal pregnancies, 19 with mild/moderate PIH and 16 with severe PIH between 28 and 39 weeks gestation. Plasma neutrophil elastase was measured by radioimmunoassay. There was a significantly higher concentration of plasma neutrophil elastase in both mild/moderate and severe PIH than in normotensive pregnancies and this may contribute to the vascular lesion associated with PIH. Concentrations were also significantly higher in normal pregnancy than in non-pregnant women which suggests that neutrophil activation and degranulation are increased in normal pregnancy.

Adult↗
PubMed1989

Increased neutrophil activation in diabetic pregnancy and in nonpregnant diabetic women.

Human neutrophil elastase may be a mediator of vascular damage, and enhanced neutrophil reactivity could contribute to the susceptibility of pregnant diabetic women to vascular complications. Elevated plasma levels of neutrophil elastase will reflect neutrophil activation in vivo. The aim of this study was to determine whether neutrophil activation occurs in uncomplicated diabetic pregnancy. We studied 30 normal nonpregnant women, 20 nonpregnant diabetic women, 32 nondiabetic women with normal pregnancies, and 17 insulin-requiring pregnant diabetic patients. Plasma neutrophil elastase was measured by radioimmunoassay. There was a significantly higher concentration of plasma neutrophil elastase in normal pregnant women compared with the nonpregnant group (P less than .001). The nonpregnant diabetic group had significantly higher concentrations than the normal nonpregnant group (P less than .002). The pregnant diabetic group had significantly higher concentrations than the nonpregnant diabetic group (P less than .001) and the normal pregnant group (P less than .05). The high concentrations of plasma neutrophil elastase may contribute to the greater sensitivity of pregnant diabetic patients to vascular complications.

Adult↗
PubMed1989

Neutrophil activation detected by increased neutrophil elastase activity in type 1 (insulin-dependent) diabetes mellitus.

Neutrophils have been implicated in the development of vascular disease, and increased plasma neutrophil elastase indicates increased neutrophil activation. The aim of this study was to determine whether neutrophil elastase levels, measured by radioimmunoassay, are altered in diabetes. One hundred Type 1 (insulin-dependent) diabetic patients and 35 comparably-aged control subjects were studied. There was no difference in the total white cell count, but the diabetic group had a higher neutrophil count (p less than 0.05). Plasma neutrophil elastase (p less than 0.001) and total neutrophil elastase (p less than 0.02) were increased in the diabetic group. The total neutrophil elastase levels reflected the neutrophil count, but plasma neutrophil elastase was independent of the number of neutrophils. The increased plasma neutrophil elastase level was not related to age, duration of diabetes, plasma glucose or HbA1. The results suggest an association between diabetes and neutrophil activation which may play a role in the development of vascular disease.

Adult↗
PubMed1988

Do extra-platelet sources contribute to the plasma level of thrombospondin?

Thrombospondin, a trimeric glycoprotein contained in the platelet alpha-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relationship between plasma thrombospondin levels and platelet count in samples from profoundly thrombocytopenic patients with marrow hypoplasia, using the platelet-specific alpha-granule protein beta-thromboglobulin as control. Serum concentrations of both proteins were highly correlated with platelet count, but while plasma beta-thromboglobulin levels and platelet count also correlated, there was no relationship between the number of platelets and thrombospondin concentrations in plasma. Serial sampling of patients recovering from bone marrow depression indicated that the plasma thrombospondin contributed by platelets is superimposed on a background concentration of at least 50 ng/ml probably derived from a non-platelet source, and plasma thrombospondin levels do not simply reflect platelet release.

Adolescent↗
PubMed1988

Measurement of the affinities of heparins, naturally occurring glycosaminoglycans, and other sulfated polymers for antithrombin III and thrombin.

Heparin, other glycosaminoglycans, and synthetic sulfated polymers have antithrombotic and anticoagulant activities, which may be mediated through a range of interactions with different proteins. A simple, quantitative method has been developed for assessing the affinity of interaction between sulfated polymers and proteins in the liquid phase. This has been used to compare the binding of a range of glycosaminoglycans and other sulfated polymers to antithrombin III and thrombin, a major inhibitor of and a central protease in the coagulation system, respectively. The results are consistent with the binding of naturally occurring glycosaminoglycans to antithrombin III solely through the well-defined antithrombin III-binding pentasaccharide found in heparin, the apparent affinity of a preparation depending upon its content of this pentasaccharide. Highly sulfated synthetic polymers will, however, bind antithrombin III by a second mechanism. The affinity of heparin for thrombin decreased with decreasing molecular weight. However, results obtained with heparan sulfate preparations did not indicate any clear relationship between either molecular weight or sulfate content and thrombin binding, but suggested that there may be an oligosaccharide sequence containing N-sulfate residues which confers high affinity for thrombin. In addition, some of the synthetic sulfated polymers bound thrombin with very high affinity.

Antithrombin III↗