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Biomedical subjects

C N Chesterman

Publications and source records attributed to C N Chesterman.

At least 127 records · Page 7Linked to original sources
PubMed1982

Further observations on the effects of dietary fatty acid composition on platelet reactivity and blood coagulation in man and the influence of methodology on findings.

Eight human subjects were fed diets enriched in saturated fat (SF), or polyunsaturated fat (PUF) and after each dietary regimen the plasma heparinthrombin clotting time (HTCT) was determined. The HTCT of citrated plasma indicated reduced heparin-neutralizing activity (HNA) after PUF feeding compared with SF feeding. Platelet factor 4 (PF4) levels in the citrated plasma samples demonstrated an inverse correlation with the HTCT (r = 0.62). Experiments with purified PF4 indicated that the PF4 present in citrated plasma could only account for approximately 10% of the HNA. Plasma prepared in a manner which minimized in vitro release of platelet constituents contained significantly less PF4 after PUF feeding and indicated that most of the PF4 found in citrated plasma resulted from in vitro release. The factor Xa inhibitory activity of citrated plasma was not significantly altered by either of the dietary regimens.

Adult↗
PubMed1982

Retrospective analysis of 158 cases of adult acute leukaemia: factors influencing prognosis and treatment response.

Discriminant and regression analyses were employed to determine the influence of a large number of clinical and laboratory indices on outcome of treatment in a series of 158 adults presenting with acute leukaemia between 1970 and 1977. Induction therapy had been most commonly cytosine arabinoside plus daunorubicin, vincristine and prednisolone. This induced complete remission in 42% of non-lymphoblastic, and in 58% of lymphoblastic plus undifferentiated leukaemias. Some induction failures who had non-lymphoblastic leukaemia were treated with cytosine arabinoside plus 6-thioguanine, which induced remissions in 46%. Advanced age was the factor most strongly associated with failure either to achieve or to sustain complete remission. Thrombocytopenia, promyelocytic leukaemia, high percentage of marrow blasts, and absence of metaphases in marrow cytogenetic preparations were also associated with poor survival. A number of other factors which appeared to be associated with poor prognosis were found by the analysis to lack significance as independent variables.

Adult↗
PubMed1982

Platelet function in coronary artery disease: effects of coronary surgery and sulfinpyrazone.

Platelet survival and plasma concentrations of beta thromboglobulin and platelet factor 4 were measured in 44 patients before and 6 months after coronary artery bypass grafting. Postoperatively, patients were randomized to receive sulfinpyrazone, 800 mg/day, or placebo. Preoperatively, platelet survival was significantly shorter than normal, and plasma concentrations of both platelet-specific proteins were significantly elevated. Postoperatively, all three indexes of platelet function tended to become normal, but these changes were statistically significant only in patients treated with sulfinpyrazone. Postoperative exercise testing correlated significantly with plasma concentrations of beta thromboglobulin and platelet factor 4 measured preoperative and postoperative. These results are consistent with reports of the effects of sulfinpyrazine on platelet involvement in other conditions, and suggest that the drug reduces platelet activation and inhibits actual destruction. The results also show a relationship between abnormalities of platelet function and an index of postoperative myocardial ischemia.

Angina Pectoris↗
PubMed1980

Complete covalent structure of human platelet factor 4.

The amino acid sequence of the subunit of human platelet factor 4 has been determined. Human platelet factor 4 consists of identical subunits containing 70 amino acids, each with a molecular weight of 7,756. The molecule contains no methionine, phenylalanine or tryptophan. The proposed amino acid sequence of PF4 is: Glu-Ala-Glu-Glu-Asp-Gly-Asp-Leu-Gln-Cys-Leu-Cys-Val-Lys-Thr-Thr-Ser-Gln-Val-Arg-Pro-Arg-His-Ile-Thr-Ser-Leu-Glu-Val-Ile-Lys-Ala-Gly-Pro-His-Cys-Pro-Thr-Ala-Gln-Leu-Ile-Ala-Thr-Leu-Lys-Asn-Gly-Arg-Lys-Ile-Cys-Leu-Asp-Leu-Gln-Ala-Pro-Leu-Tyr-Lys-Lys-Ile-Ile-Lys-Lys-Leu-Leu-Glu-Ser. From consideration of the homology with beta-thromboglobulin, disulphide bonds between residues 10 and 36 and between residues 12 and 52 can be inferred.

Amino Acid Sequence↗
PubMed1980

Heparin-associated thrombocytopenia: case report and prospective study.

After observing a patient with heparin-induced thrombocytopenia we prospectively recorded the incidence of thrombocytopenia associated with heparin treatment by measuring the platelet count every second day in 166 patients given therapeutic heparin for various thromboembolic disorders, and 51 patients given low-dose heparin prophylaxis. A platelet count below 100 x 10(9)/litre developed in nine patients (5.4%) during or soon after full-dose heparin therapy, and in one patient given low-dose heparin. Careful clinical review suggested that heparin was either the most likely cause of a contributing cause of thrombocytopenia in 5/166 patients (3.0%) receiving therapeutic heparin and none of the patients who received prophylactic heparin. Associated laboratory studies suggest that heparin-initiated platelet aggregation in vivo is a useful marker for heparin-induced thrombocytopenia.

Adult↗
PubMed1980

Plasma concentrations of platelet-specific proteins correlated with platelet survival.

Relationships between 51Cr platelet survival and plasma concentrations of beta-thromboglobulin (betaTG) and platelet factor 4 (PF4) were analyzed in 91 studies of patients with coronary artery disease. betaTG was significantly correlated with platelet life-span, turnover, and the number of hits in the multiple hit model. PF4 was significantly correlated with life-span and turnover. The most significant relationship involving platelet-specific protein concentrations and life-span estimates was between betaTG and life-span estimated using the multiple hit model (r = -0.39, p less than 0.001). There was a high correlation between betaTG and PF4 (r = 0.62, p less than 0.001), and no improvement could be obtained by combining the measurements of the two proteins in any regression with life-span or turnover. The results indicate that the patients with the shortest platelet survival time in this group tended to have the highest plasma concentration of betaTG and PF4 and thus probably increased in vivo release of betaTG and PF4. They strengthen the claim that these platelet-specific proteins may be indicators of platelet involvement in disease.

Blood Platelets↗
PubMed1979

Detection of deep venous thrombosis by scanning of 99mtechnetium-labelled red-cell venous pool.

A comparative study of 32 patients with suspected deep venous thrombosis was carried out using blood-pool radionuclide scanning and conventional x-ray phlebography. Results of the two methods showed close agreement, the sensitivity (positive correlation) of the scan being 100% and its specificity 89%. We conclude that a patient's red cells labelled with 99mtechnetium (99mTc) provide an excellent medium for this type of scanning. The technique has particular advantages in visualising the whole venous system, giving a persisting image, and obviating the need to inject into a vein of the affected limb. In view of the inherent disadvantages of contrast phlebography, 99mTc-red-cell scanning is clearly an acceptable alternative.

Erythrocytes↗
PubMed1978

Complete covalent structure of human beta-thromboglobulin.

The complete primary structure of the platelet-specific protein human beta-thromboglobulin has been determined. beta-Thromboglobulin consists of identical subunits of 81 amino acids, each with a molecular weight of 8851. The amino acid sequence of the beta-thromboglobulin subunit is: Gly-Lys-Glu-Glu-Ser-Leu-Asp-Ser-Asp-Leu-Tyr-Ala-Glu-Leu-Arg-Cys-Met-Cys-Ile-Lys-Thr-Thr-Ser-Gly-Ile-His-Pro-Lys-Asn-Ile-Gln-Ser-Leu-Glu-Val-Ile-Gly-Lys-Gly-Thr-His-Cys-Asn-Gln-Val-Glu-Val-Ile-Ala-Thr-Leu-Lys-Asp-Gly-Arg-Lys-Ile-Cys-Leu-Asp-Pro-Asp-Ala-Pro-Arg-Ile-Lys-Lys-Ile-Val-Gln-Lys-Lys-Leu-Ala-Gly-Asp-Glu-Ser-Ala-Asp. Disulfide bridge-18 to half-cystine-58. The amino acid sequence of beta-thromboglobulin shows a marked homology with that of platelet factor 4. When the sequences are aligned for maximum homology, 42 of the 81 residues of beta-thromboglobulin are identical with those of platelet factor 4, including the position of the four half-cystines.

Amino Acid Sequence↗
PubMed1978

Plasma levels of platelet factor 4 measured by radioimmunoassay.

A radioimmunoassay has been developed to measure platelet factor 4 (PF4) in biological fluids both in vitro and in vivo. The assay has been shown to be highly specific for PF4 and has a sensitivity of 0.08 ng/assay tube and 1.6 ng/ml of plasma. The preparation of plasma for the measurement of in vivo levels of PF4 requires the use of an anticoagulant containing EDTA, theophylline and prostaglandin E1, the immediate cooling of the blood and high speed or prolonged centrifugation to reduce platelet contamination. Plasma levels of PF4 are normally between 4 and 24 ng/ml with a median of 7.4 ng/ml. Plasma PF4 levels are markedly increased during cardiopulmonary bypass surgery with shortened 51Cr-labelled platelet survival times and during arterial thrombosis. However, despite similarly shortened platelet survival times, the level of PF4 is normal in immune thrombocytopenia. Elevations of plasma PF4 levels are found following surgery, acute myocardial infarction and frequently during acute infections and in inflammatory states. On the contrary, normal levels are usual in disseminated malignancy, in severe hepatic and renal disease and in chronic arterial disease. The measurement of PF4 is a useful addition to the study of platelet pathophysiology. It is apparent, however, that raised levels are by no means specific for thromboembolic disease and similarly platelet destruction is not invariably associated with abnormally increased plasma PF4 levels.

Adult↗
PubMed1977

Controlled trial of the sequential use of streptokinase and ancrod in the treatment of deep vein thrombosis of lower limb.

Treatment with streptokinase ('Kabikinase') was given to 26 patients with venographically confirmed deep vein thrombosis extending into the popliteal vein or above. Treatment was continued for 4 days and the patients were allocated randomly to oral anticoagulant therapy or a course of treatment with ancrod ('Arvin') for 6 days followed by oral anticoagulant therapy. The degree of thrombolysis as judged by further venographic examination at 10 days was not significantly different between the 2 groups. The majority of patients showed clinical improvement but there was no appreciable difference between the groups at 3 and 6 months. Haemorrhagic complications were a more serious problem during the period of treatment with ancrod than during the equivalent period in the control group.

Ancrod↗
PubMed1977

Studies on the chemistry of human platelet factor 4.

The chemical characteristics of several PF4 preparations have been examined by gel electrophoresis, amino acid analysis and NH2-terminal amino acid sequence determination. Preparations of PF4 from gel filtration and from affinity chromatography appeared identical. A single NH2-terminal sequence was determined as follows: NH2-Glu-Ala-Glu-Glu-Asp-Gly-Asp-Leu-Gin-SCMCys-Leu-SCMCys-Val-Lys-Thr-Thr-Ser-Gln-Val-Arg-. The molecular weight of the PF4 subunits, which seem to be identical, was 7,100 based on the recovery of NH2-terminal glutamic acid.

Amino Acid Sequence↗
PubMed1976

Pulmonary embolism: current therapeutic concepts.

Pulmonary thromboembolism is a widespread problem and is an important cause of death in patients with a variety of medical and surgical conditions. There have been few significant advances in the understanding of the aetiology beyond additional evidence confirming the importance of Virchow's triad. An impressive list of epidemiological associations has been compiled, however. Some knowledge of the natural progression of the disease is required as an aid in the understanding of the application of the therapeutic and prophylactic measures available in the management of pulmonary embolism. It would seem that at least two-thirds of pulmonary emboli are non-fatal, and in these cases the natural resolution, even of comparatively large embolic masses, is very efficient in patients without pre-existing cardiopulmonary disease. Diagnosis may prove difficult and most ancillary investigations are of questionable value. On the other hand, pulmonary radio-isotope scanning is far more specific and pulmonary angiography is a comparatively simple and complication-free diagnostic procedure. Prophylaxis is a real and practical aim, especially following surgery or myocardial infarction. In these groups widespread clinical trials of prophylactic measures have been made possible by the objective radio-iosotope screening techniques. Mechanical means of preventing venous stasis and anticoagulation appear effective. In addition, low-dose subcutaneous heparin seems to be as useful as heparin in conventional dosage. Apart from conventional supportive therapy, there are three major approaches to the treatment of pulmonary embolism. Heparin remains the mainstay, particularly in the less severe cases, hopefully preventing propogation of thrombosis and recurrence of embolism, thus allowing resolution to take place. Thrombolytic therapy with streptokinase or urokinase is capable of producing far more rapid dissolution of pulmonary emboli with consequent theoretical advantages over heparin. No reduction in mortality has been shown using thrombolytic therapy. Patients who fail to respond satisfactorily to acute resuscitative measures may require pulmonary embolectomy.

Chronic Disease↗
PubMed1975

The fibrinolytic system and haemostasis.

The fibrinolytic enzyme system appears to be a parallel development with the plasma coagulation pathways involved in haemostasis. Both systems have common activation mechanisms, inhibitors and the enzymes involved have considerable homology. In addition, blood cells show capabilities for involvement in each of these systems. There is disagreement over the possible contribution of the fibrinolytic mechanism to normal fibrinogen catabolism either by the lysis of continually forming fibrin, or by degradation of circulating fibrinogen. The occurrence of systemic fibrinolysis is associated with haemorrhagic tendency which may be due to a number of factors including degradation of coagulation factors, the anticoagulant effect of F.D.P. and the lysis of alpha-chain crosslinking sites. A clinical study of patients treated with streptokinase indicates that a fall in plasma fibrinogen levels and increase in serum F.D.P. levels are correlated with the haemostatic defect.

Blood Cells↗
PubMed1975

Measurement of fibrinogen-fibrin-related antigen in serum as aid to diagnosis of deep vein thrombosis in outpatients.

A study of serum levels of fibrinogen-fibrin-related antigen (F.R.-antigen) in outpatients presenting with clinical features suggesting deep vein thrombosis was undertaken. A raised serum level of this antigen (greater than 12 mg/1) is strong evidence in favour of the diagnosis of deep vein thrombosis. It is virtually conclusive evidence if other known causes of a raised level of the antigen are absent. On the other hand, a normal serum level of F.R.-antigen does not exclude even extensive thrombosis, and other objective techniques are required to substantiate the diagnosis.

Adult↗