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Biomedical subjects

M F Scully

Publications and source records attributed to M F Scully.

At least 109 records · Page 6Linked to original sources

Low-molecular-weight heparin and prevention of postoperative deep vein thrombosis.

The efficacy of low-molecular-weight heparin as a prophylactic agent was assessed in 150 consecutive patients over the age of 40 undergoing major abdominal surgery. Fifty of these patients received 1250 activated partial thromboplastin time (APTT) units of low-molecular-weight heparin every 12 hours: three developed isotopic deep vein thrombosis, which was confirmed by phlebography in two cases. The other 100 patients received a single injection of 1850 APTT units of low-molecular-weight heparin. Three of them developed isotopic deep vein thrombosis; phlebography failed to confirm the presence of thrombi in each case. None of the 150 patients studied died from fatal or contributory pulmonary emboli. Low-molecular-weight heparin was not associated with any increase in preoperative or postoperative bleeding. The effect of equal amounts of postoperative bleeding. The effect of equal amounts of low-molecular-weight heparin and unfractionated heparin on the coagulation mechanism during surgery was investigated in another 30 patients. The clotting assays and results of in-vivo platelet function tests indicated that both preparations produced similar effect. Intragroup comparisons, however, showed significant differences in the anti-factor Xa activity, lipoprotein lipase release, and plasma prekallikrein concentrations. A single injection of low-molecular-weight heparin daily is a convenient way of preventing deep vein thrombosis in high-risk patients undergoing major abdominal surgery.

Adult↗

Structural features of fibrinogen associated with binding to chelated zinc.

Fibrinogen absorbed to zinc chelate columns at pH 7.8 and was eluted sharply with a pK of 5.8 indicative of the involvement of a histidine residue. The binding was unaffected by high concentrations of calcium or zinc. Fibrinogen degradation products X and Y also bound to zinc chelate columns. On passage of fibrinogen fragments D and E through these columns fragment E was not bound and fragment D was eluted subsequently in a pure form with a pK of 6.1.

Binding Sites↗

An acquired coagulation inhibitor to factor II.

An elderly woman with a bleeding problem associated with prolonged PTT, PT and thrombin time but with normal snake venom time was found to have very high levels of plasma antithrombin. The antithrombin activity was isolated and characterized and found to be an IgG which directly inhibited thrombin and also precipitated prothrombin. The concentration in plasma of the gamma-globulin inhibitory activity was equivalent per ml to 80 NIH units of thrombin. Corticosteroid and immunosuppressive treatment reduced the level of the inhibitor with remission of bleeding symptoms.

Aged↗

The problem of infection after prostatic biopsy: the case for the transperineal approach.

The incidence of infection after needle biopsy of the prostate by different techniques was compared in 45 patients. Aerobic and anaerobic culture was made of the biopsy needle, prostate, urine and blood. In addition, endotoxin assays were determined by a new chromogenic method using Limulus lysate. All of the patients undergoing transrectal biopsy were found to have a bacteraemia; 27% were symptomatic and 87% had a post-operative urinary tract infection. A double-blind controlled trial using cefamandole with the premedication showed a significant reduction in the incidence of bacteraemia to 53% and the prevention of a urinary tract infection. Following transperineal biopsy, although the incidence of bacteraemia was 40% and urinary tract infection 27%, none of these patients was symptomatic and the organisms causing the bacteraemia were predominantly skin contaminants. The endotoxin assays showed differences between the groups with higher endotoxin values in the unprotected transrectal group.

Bacteria↗

Do prostacyclin and thromboxane play a role in endotoxic shock?

The role of prostacyclin and thromboxane during endotoxic shock is unknown. Using new radioimmunoassay techniques, we have studied the plasma levels of stable metabolites of prostacyclin (6-keto-PGF1 alpha) and thromboxane (TxB2) in a porcine model of endotoxic shock. TxB2 levels were markedly elevated but the production of prostacyclin appears to be impaired. Correction of this prostanoid imbalance by the infusion of prostacyclin or pre-treatment with a specific thromboxane synthetase inhibitor produces significant and beneficial effects on blood pressure and pre-kallikrein activation.

6-Ketoprostaglandin F1 alpha↗

Hereditary antithrombin III deficiency in an English family.

A family including four members with decreased antithrombin III (ATIII) measured by a biological and an immunological method is described. Immunologically measured levels of other coagulation inhibitors were normal. In the antithrombin III deficient family members there was a history of thrombotic disease. Turnover of 125I-antithrombin III in a deficient individual showed the lower plasma levels probably to be due to a deficiency in the rate of synthesis rather than to an increased catabolic rate.

Adult↗

Enhanced in-vivo platelet release reaction, increased thromboxane synthesis, and decreased prostacyclin release after tourniquet ischaemia.

Plasma beta-thromboglobulin (beta-TG), a marker of in-vivo platelet release reaction, was measured in 27 meniscectomy patients, 10 patients who underwent total knee replacements (TKR) (both procedures performed under tourniquet ischaemia), and 10 herniorrhaphy patients. In 22 meniscectomy and 7 TKR patients plasma-thromboxane-B2 (TxB2), a stable end-product of thromboxane-synthetase activity, was also determined. The mean plasma beta-TG and TxB2 had risen significantly within 5 min of release of the tourniquet, indicating increased in-vivo platelet release reaction and prostaglandin synthesis in these patients. In the herniorrhaphy patients beta-TG and TxB2 did not alter significantly postoperatively. In 6 pigs (weighing 20-30 kg) who underwent meniscectomy under tourniquet ischaemia plasma TxB2 rose significantly 15-30 min after release of the tourniquet, and prostacyclin release was significantly lower from veins exposed to ischaemia than from control veins. Large de-endothelialised areas were seen on scanning electron-micrographic sections of affected veins, and these areas were covered with a monolayer of platelets and platelet clumps. These changes associated with tourniquet ischaemia may explain the high incidence of venous thrombosis seen in patients undergoing meniscectomy and TKR.

Adult↗

Methods for semi micro or automated determination of thrombin, antithrombin, and heparin cofactor using he substrate, H-D-Phe-Pip-Arg-p-nitroanilide-2HCl.

Methods for the measurement of thrombin and plasma antithrombin, by end point determination at a semi micro level and also by rate assay measurement in a fully automated system have been devised using the thrombin specific chromogenic substrate, H-D-Phe-Pip-Arg-p-nitroanilide. Preliminary defibrination of plasma is avoided in both methods. The semi micro method has been correlated with antitrhombin measured in plasma of postoperative patients by established clotting and immunological assays. The automated method has been found to be highly reproducible and to have less scatter than the other procedures.

Alpha-Globulins↗

Intermittent plasminogen-streptokinase treatment of deep vein thrombosis.

The fibrinolytic response of 12 patients receiving single daily infusions of 600,000 units of streptokinase (SK) and 90 mg of plasminogen for the treatment of DVT has been studied. The mean plasminogen concentration was maintained throughout the treatment period (4-6 days) at between 20-40% the initial value, while mean circulating plasmin concentration rose to only about twice initial plasma levels. The degradation of fibrinogen as indicated by a fall in clottable fibrinogen did not fall below 1 mg/ml and serum FDP rose to greater than 1 mg/ml. Limited fibrinogenolysis occurred in 2 patients, while in another patient who bled there was immediate and extensive depletion to below 0.5 mg/ml. The beneficial clinical results obtained with this regimen (Kakkar et al. 1975), which produces only limited systemic plasminaemia, suggest that thrombolysis may be facilitated by higher levels of plasminogen than those maintained during conventional SK treatment.

Fibrin Fibrinogen Degradation Products↗

Acquired dysfibrinogenaemia in acute and chronic liver disease.

Plasma from patients with both acute and chronic liver disease has been examined for evidence of acquired dysfibrinogenaemia, using electrophoretic methods and coagulation tests. An examination of isolated fibrins upon SDS polyacryamide gel electrophoresis failed to demonstrate any molecular or structural defect associated with the polypeptide chains of the patients' fibrinogen or fibrinogen derivatives produced by thrombin or plasmin. However, purified fibrin monomers isolated from plasma using both Reptilase and thrombin exhibited delayed polymerization rates and the occurrence of acquired dysfibrinogenaemia in liver disease is therefore confirmed.

Acute Disease↗