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Biomedical subjects

M Greaves

Publications and source records attributed to M Greaves.

At least 19 recordsLinked to original sources

Relationships between haemostatic factors and capillary morphology in human diabetic neuropathy.

We have examined haemostatic factors in 15 diabetic patients with peripheral neuropathy and 10 diabetic patients without clinical complications. Plasma and blood viscosity, fibrinogen, factor VIIIc, von Willebrand factor activity, spontaneous platelet aggregation and fibrinolytic activity were not significantly different between diabetic patients without clinical complications and diabetic patients with peripheral neuropathy. Platelet aggregation was enhanced in diabetic patients with neuropathy compared with those without complications. In the 15 patients with neuropathy and 3 without complications, who underwent biopsy of sural nerve, skin and muscle, associations were found between haemostatic variables and measures of nerve capillary pathology, notably: plasma fibrinogen and nerve capillary basement membrane thickness (r = 0.70, p < 0.001); thromboxane B2 production and nerve capillary basement membrane thickness (r = -0.61, p < 0.01); plasma fibrinolytic activity and endoneurial capillary lumen size (r = 0.60, p < 0.01) and endothelial cell outer perimeter (r = 0.65, p < 0.01). The main associations of skin and muscle capillary abnormalities were with measures of in vitro platelet aggregation, and the correlations found with nerve capillary measurements were not echoed in the overlying muscle and skin. The results are supportive of the involvement of haemostatic abnormalities in the pathogenesis of diabetic neuropathy.

Adult

Serum masks the inhibition of thrombin-induced prostacyclin release produced by anticardiolipin antibodies.

The effect on thrombin-induced release of prostacyclin from human umbilical vein endothelial cells of preincubation with both serum and serum derived from platelet-poor plasma (PDS) from patients with systemic lupus erythematosus (SLE), systemic sclerosis, the antiphospholipid syndrome (APS) and normal controls was examined. Although no significant differences in thrombin-induced prostacyclin release were found in any of the patient groups, further analysis revealed that PDS from patients with SLE and APS that contained IgG anticardiolipin antibodies produced significant inhibition of prostacyclin release when compared with controls (P = 0.02). The effect was maximal with samples that contained both IgG and IgM anticardiolipin antibodies (P less than 0.01) and which had a significantly higher titre of IgG antibodies than samples which contained solely IgG antibodies (P less than 0.05). The absence of any corresponding inhibition of prostacyclin release by serum samples that contained anticardiolipin antibodies, possibly due to the release of masking stimulatory factors by platelets during coagulation, provides an explanation for the conflicting nature of previous reports.

Adult

Guidelines for the use of fresh frozen plasma. British Committee for Standards in Haematology, Working Party of the Blood Transfusion Task Force.

Fresh frozen plasma should only be used to treat bleeding episodes or prepare patients for surgery in certain defined situations. Definite indications for the use of FFP: 1. Replacement of single coagulation factor deficiencies, where a specific or combined factor concentrate is unavailable. 2. Immediate reversal or warfarin effect. 3. Acute disseminated intravascular coagulation (DIC). 4. Thrombotic thrombocytopenic purpura (TTP). Conditional uses: FFP only indicated in the presence of bleeding and disturbed coagulation: 1. Massive transfusion. 2. Liver disease. 3. cardiopulmonary bypass surgery. 4. Special paediatric indications. No justification for the use of FFP: 1. Hypovolaemia. 2. Plasma exchange procedures. 3. 'Formula' replacement. 4. Nutritional support. 5. Treatment of immunodeficiency states.

Adult

Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption.

We studied bone biopsies from 26 patients with myelomatosis with apparently normal skeletal metabolism. Quantitative histomorphometric measurements suggested that skeletal disease was progressive despite normocalcaemia and normal urinary excretion rates of calcium and hydroxyproline. When biopsies were divided according to the involvement of marrow by plasma cells, bone resorption--as judged by the eroded surface--increased significantly the greater plasma cell burden. Osteoclasts were frequent with moderate tumour burdens, but there was no further increase in the number of osteoclasts when plasma cell infiltration increased by more than 50% of bone marrow. Contrary to expectation, the numbers of osteoblasts and bone formation rates were increased with bone biopsies with moderate tumour burden, but were markedly lower when plasma cell infiltration occupied more than 50% of bone marrow, due to a decreased functional capacity of osteoblasts. We conclude that skeletal bone disease in myeloma is commonly progressive despite apparently stable bone disease as judged by biochemical measurements. The major mechanism of bone loss in myelomatosis is increased osteoclastic resorption but decreased bone formation contributes to bone loss with heavy plasma cell burdens. Urinary excretion of calcium and hydroxyproline provide insensitive indices of bone resorption in myelomatosis.

Alkaline Phosphatase

Isolation of circulating megakaryocytes in man.

Recovery of the small numbers of megakaryocytes (MKs) known to be present in normal blood is difficult because of their low frequency. Isolation of circulating MKs was achieved using a modified filtration system in which untreated blood was passed through 5 microns polycarbonate membranes. MKs were retained while most other blood cells passed through the membranes. Four groups of MKs were identified in May Grünwald-Giemsa stained filters of blood from peripheral, central and umbilical veins and umbilical arteries. Type 1 MKs were nuclei with no visible cytoplasm. Types 2, 3 and 4 were nuclei with increasing amounts of cytoplasm. Type 4 MKs, possessing copious cytoplasm, were rarely isolated from peripheral venous blood but were more regularly encountered in central venous and cord blood. Filtration of whole blood through polycarbonate membranes is a useful technique for the isolation of circulating MKs, which are a normal physiological occurrence. Their presence is consistent with the production of platelets in the placenta during intra-uterine life, and subsequently in the pulmonary circulation.

Hemofiltration

Angioedema: manifestations and management.

Angioedema is characterized by localized swelling of sudden onset affecting the skin and/or mucous membranes. It can be classified into hereditary and acquired forms. Hereditary angioedema is a rare disease inherited as an autosomal dominant trait and caused by a deficiency of C1-esterase inhibitor. Acute attacks are life threatening and cannot be managed by antihistamines, corticosteroids, or adrenergic drugs. Prophylactic therapy is possible with danazol or stanozolol. Acquired angioedema includes nonhereditary C1-esterase inhibitor deficiency; idiopathic, allergic, and drug-induced forms; angioedema associated with lupus erythematosus and hypereosinophilia; and angioedema caused by physical stimuli. Treatment of these forms of angioedema depends on identifying and avoiding the cause, induction of tolerance, or symptomatic treatment with systemic antihistamines.

Angioedema

Lupus anticoagulant.

Acquired antibodies to phospholipids form a heterogeneous group, which may be detected in vitro by the inhibition of phospholipid dependent tests of coagulation (lupus anticoagulant) and also by immunological assays, such that a combined approach is required for their reliable detection. While initially described in sufferers from systemic lupus erythematosus, these antibodies are increasingly recognised in a broad spectrum of disease, most importantly in relation to thromboembolism and recurrent fetal loss; occasionally they may also be found in otherwise healthy individuals. The mechanisms underlying the prethrombotic state associated with these antibodies have not been defined, although interference with the natural anticoagulant systems seems possible. Identification of antiphospholipid in subjects with spontaneous thromboembolism may influence therapeutic decisions, while their presence in women with recurrent fetal loss has lead to attempts to alter the outcome of further pregnancies with anticoagulant and immunosuppressive regimens, however the optimum management has not yet been determined. The recognition of these antibodies and their clinical associations is therefore highly relevant to clinical and laboratory haematology.

Humans

Antiphospholipid antibodies in the aetiology of ischaemic optic neuropathy.

The involvement of antiphospholipid antibodies in the mediation of acute anterior ischaemic optic neuropathy (AION) was studied, in the light of recent associations between these autoantibodies and other vascular events. A strong association between IgG anticardiolipin antibodies and AION secondary to biopsy proven giant cell arteritis was identified, which did not exist with the 'non-arteritic', biopsy negative form of AION. The possible implications of this finding on the aetiology, diagnosis, and treatment of giant cell arteritis are discussed.

Acute Disease

Immediate-pressure urticaria--a distinct disorder.

We report a patient who has an immediate wealing response to pressure in the absence of symptomatic dermographism, which we designate 'immediate-pressure urticaria'. Our patient also suffered from cholinergic urticaria and chronic idiopathic urticaria in the past, demonstrating the clustering of urticarias which frequently occurs.

Female

Inter-relationships between platelet count, platelet IgG, serum IgG, immune complexes and severity of liver disease.

Thrombocytopenia is a common finding in subjects with chronic liver diseases. A variety of mechanisms may underlie this. Immunological disturbances are commonly a feature in chronic liver disease, including hyperglobulinaemia and the presence of autoantibodies and circulating immune complexes and immune mechanisms could therefore contribute to thrombocytopenia. We have investigated the relationships between blood platelet count, serum IgG and IgG immune complexes and IgG associated with platelets in 92 subjects with chronic liver disease (27 with chronic active hepatitis, 38 with primary biliary cirrhosis and 27 with alcoholic liver disease). Severity of liver impairment was a major determinant of degree of thrombocytopenia. Also, an inverse relationship was demonstrated between platelet count and platelet-associated IgG. In subjects with chronic active hepatitis the relationships between platelet count, serum IgG immune complexes and platelet-associated IgG were consistent with a role for immune mechanisms in general and immune complexes in particular as mediators of the thrombocytopenia.

Antigen-Antibody Complex

The effects of diet and insulin therapy on coagulation factor VII, blood viscosity, and platelet release proteins in diabetic patients with secondary sulphonylurea failure.

The effect of intensified dietary measures and subsequently insulin therapy upon haemorheological measures were studied in Type 2 diabetic patients with secondary sulphonylurea failure. Coagulation factors VIIc and VIIIc, fibrinogen, plasma viscosity, whole blood viscosity, beta-thromboglobulin, platelet factor 4, von Willebrand factor, and euglobulin clot lysis time were measured at baseline, after 3 months intensified dietary therapy and after 4 months insulin therapy. During intensified dietary therapy there was a significant fall in serum cholesterol (p less than 0.05) and a small decrease in weight, but no significant change in blood glucose control. Factor VIIc levels fell significantly (1.22 (SE 0.07) vs 1.42 (0.08) u ml-1, p less than 0.01), and plasma viscosity and whole blood viscosity (23 s-1) also improved (both p less than 0.05). Insulin therapy was instituted with either continuous subcutaneous insulin therapy or twice daily injections of soluble and isophane (NPH) insulin. During this period glycosylated haemoglobin improved (mean (SE) 49.5 (1.4) vs 65.0 (2.1) mmol-HMF mol-Hb-1, p less than 0.001; normal range 29-39 mmol-HMF mol-Hb-1) as did serum triglyceride (p less than 0.01), but weight increased (p less than 0.001). The only haemorheological changes with insulin were increased levels of the platelet release proteins beta-thromboglobulin (37 (3) vs 28 (2) micrograms l-1, p less than 0.01) and platelet factor 4 (median 7.5 (range 3.0-18.0) vs 4.5 (2.0-10.5) micrograms l-1, p less than 0.01).

Adult

Screening for lupus anticoagulant and anticardiolipin antibodies in women with fetal loss.

Sixty six women with first or second trimester fetal loss were investigated for the presence of lupus anticoagulant by routine coagulation tests and the dilute Russell's viper venom time with a platelet neutralisation procedure, and for raised anticardiolipin antibodies by an enzyme linked immunosorbent assay. Of 35 women with recurrent fetal loss, seven were positive for lupus anticoagulant and six had increased IgG anticardiolipin antibodies, while of 31 women with only one or two episodes of fetal loss, one had lupus anticoagulant and none increased IgG anticardiolipin antibodies. These findings were significantly different. There was no difference in the incidence of increased IgM anticardiolipin antibodies between the two groups (three and two cases, respectively). A further 11 women with intrauterine death in the third trimester were studied and lupus anticoagulant and raised IgM anticardiolipin antibodies were found in one case. No woman was known to have systemic lupus erythematosus. It is concluded that lupus anticoagulant and increased IgG anticardiolipin antibodies are independently associated with recurrent first and second trimester fetal loss and that such cases should be investigated, even in the presence of otherwise good health, by a comprehensive methodological approach.

Abortion, Habitual

Bone marrow aplasia in B cell chronic lymphocytic leukaemia: successful treatment with antithymocyte globulin.

Pure red cell aplasia is a rare but well known association of chronic lymphocytic leukaemia (CLL). Pancytopenia due to bone marrow aplasia has not been previously described in CLL. A 42 year old man with B cell CLL became severely pancytopenic with bone marrow aplasia. Bone marrow culture resulted in a greatly reduced colony formation. High dose corticosteroids and intravenous immunoglobulin treatment were unsuccessful. Prompt and complete marrow recovery ensued after administration of antithymocyte globulin.

Adult