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Biomedical subjects

M J Mackie

Publications and source records attributed to M J Mackie.

50 records · Page 3Linked to original sources
PubMed1984

Fibronectin C in acute leukaemia.

Fibronectin C (FN:C) is thought to represent fibronectin complexed with other plasma proteins and can be detected by a crossed two-dimensional immunoelectrophoretic technique. While we have not detected this on examination of normal plasma, FN:C was found in 26 of 33 patients (79%) with acute leukaemia at diagnosis. FN:C persisted throughout the induction phase of chemotherapy and disappeared only when a complete remission was obtained in 16 of 17 FN:C+ patients. FN:C has reappeared in the only patient whose leukaemia has relapsed to date. FN:C was present in both acute non-lymphoblastic (85%) and acute lymphoblastic leukaemia (50%). Leukaemia remission rates were similar in patients who were FN:C+ or FN:C- (69% and 57%). Evidence is presented to suggest that the composition of FN:C is partially related to the binding of fibrinogen/fibrin to fibronectin in plasma. No significant difference in in vivo activation of coagulation was detected between FN:C+ and FN:C- patients. There was no correlation between the presence of FN:C and plasma fibronectin levels.

Adult↗
PubMed1983

Skin infiltration associated with chronic myelomonocytic leukaemia.

Chronic myelomonocytic leukaemia (CMML) is typically associated with a prolonged clinical course and is not usually very responsive to chemotherapeutic intervention. Skin infiltration has not been recognized previously as a feature of this illness. We have seen four patients recently with CMML, who during the the course of their illness developed marked skin infiltration. Whilst sensitivity to chemotherapy could be demonstrated in the peripheral blood cell population, skin infiltration was quite resistant to treatment. Skin infiltration heralded a more aggressive phase of the disease although no discernible change in morphology, cytochemistry or membrane marker analysis of the leukaemic cell population could be demonstrated in three of the patients studied; one patient, however, transformed to an acute leukaemia shortly thereafter.

Aged↗
PubMed1983

Circulating plasmin-antiplasmin complexes in acute leukaemia.

Thirty consecutive patients presenting with acute leukaemia were studied throughout their hospital course to determine if plasma-alpha 2 antiplasmin (P-AP) complexes could be detected during episodes of increased fibrinolytic activity and to correlate this finding with other more conventional laboratory parameters. Increased fibrinolytic activity was a common finding, it was detected in 19 (63%) patients. This was usually present at diagnosis, but occasionally occurred later as a transient phenomenon. Increased fibrinolytic activity could not clearly be associated with either infection or chemotherapy. P-AP complexes were found in 11 (37%) patients and were almost always accompanied by additional laboratory evidence of increased fibrinolysis. These complexes were present in most instances at diagnosis and disappeared following successful chemotherapy. Forty-five per cent of patients with P-AP complexes had low alpha 2-antiplasmin levels and 36% had low plasminogen levels which returned to normal following successful chemotherapy. At diagnosis six of eight patients with P-AP complexes had major haemorrhagic manifestations.

Acute Disease↗
PubMed1983

Fibronectin in blood products--an in vitro and in vivo study.

The concentration of fibronectin was assessed in a variety of coagulation factor preparations. Highest concentrations of fibronectin were found in the intermediate purity factor VIII concentrates. Significant amounts were found in cryoprecipitate but high purity factor VIII concentrates contained only small amounts. For practical purposes factor IX concentrates contained no fibronectin. Qualitative estimation of fibronectin showed the presence of an abnormal slow migrating peak on 2 DIEP which was not found in normal plasma. In vivo recovery infused fibronectin was relatively low for all products studied (30-54%). The plasma half life (17-25 h) did not differ significantly depending on whether cryoprecipitate or a factor VIII concentrate was used as a source of fibronectin. No enhancement of plasma fibronectin concentrations was obtained following DDAVP infusion, venous occlusion and exercise. Plasma fibronectin concentrations and 2 DIEP patterns were unaltered following prolonged storage.

Blood Coagulation Factors↗
PubMed1983

Chronic inflammatory bowel disease, deep-venous thrombosis and antithrombin activity.

Of 34 patients with chronic inflammatory bowel disease (CIBD), 4 developed well-documented episodes of deep-venous thrombosis. All 4 patients had active disease at the time of thrombosis. This group was studied to determine if the tendency to deep-venous thrombosis in patients with CIBD was associated with reduced antithrombin activity by measuring the concentration of three thrombin inhibitors, antithrombin III (AT III), alpha 2-macroglobulin (alpha 2 M) and alpha 1-antitrypsin. 2 patients had low AT III levels and 10 had low alpha 2 M levels. 2 patients who developed deep-venous thrombosis had significantly low levels of both AT III and alpha 2 M. It is suggested that in patients with diseases predisposing to thrombosis and associated with low AT III levels, the measurement of alpha 2 M in addition to AT III may predict those particularly at risk.

Antithrombin III↗
PubMed1983

Combinations of increased thrombin, plasmin and non-specific protease activity in patients with acute leukaemia.

Thrombin generation, plasmin formation and non-specific protease activity, were assessed in a cohort group of 30 patients presenting with acute leukaemia. Abnormalities detected by specific tests of one or more of these three systems were found in 27 (90%) of patients while abnormalities in 'routine' laboratory coagulation tests were seen in only 17 (56%). All patients at presentation had a bleeding tendency which was defined as minor (skin purpura) or major (other bleeding sites). Patients presenting with minor (n = 19) or major haemorrhage (n = 11) could not be differentiated by the degree of thrombocytopenia. Similarly, increased generation of either thrombin or plasmin activity alone was non-discriminatory. However, more complex alterations of haemostasis involving increased activity of more than one of these three systems were seen only in those patients who had major haemorrhage.

Acute Disease↗
PubMedDate not supplied

Prospective study of the safety and financial benefit of ketoconazole as adjunctive therapy to cyclosporine after heart transplantation.

In a prospective study of the relative safety and potential benefit of concomitant ketoconazole and cyclosporine after heart transplantation, 15 transplant recipients were followed up for up to 1 year (mean, 10.7 months) after ketoconazole was added to their immunosuppressive regimen of cyclosporine, prednisone, and azathioprine, and these patients were compared with a matched cohort over the same time. There was an 88% reduction in the mean (+/- SD) dose of cyclosporine, from 394 (115) mg/day to 47 (21) mg/day (p less than 0.0005) in the ketoconazole group, compared with an insignificant change in the control group. The projected annual cost of cyclosporine was reduced by 88%, with a 72% reduction in the projected cost of immunosuppressive drugs and prophylactic antifungal therapy, from a mean of $6800 to $1862 per year per transplant recipient in the ketoconazole-treated group. Other beneficial effects found over the study period included a significant reduction in the mean and diastolic systemic arterial pressure and a significant reduction in serum cholesterol. The mean total serum cholesterol fell from 265 (44) to 204 (38) mg/dl in the ketoconazole group but did not change significantly in the control group (p less than 0.005). Low-density lipoprotein cholesterol also fell from a mean of 167 (32) mg/dl to 112 (28) mg/dl (p less than 0.005). Renal function was not significantly affected by ketoconazole when compared with the control group. Ketoconazole and other drugs of potential use in organ transplant recipients should be evaluated for financial as well as for other potential clinical benefits in the long-term management of these patients.

Azathioprine↗