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Biomedical subjects

J Gram

Publications and source records attributed to J Gram.

At least 127 records · Page 7Linked to original sources

Does protamine chloride neutralize low molecular weight heparin sufficiently?

The heparin neutralizing properties of protamine chloride on conventional heparin (porcine mucosa) and on low molecular weight heparin (Kabi 2165) were studied in vitro. Protamine chloride neutralized 99% of the delaying effect of conventional heparin on the activated partial thromboplastin time, whereas only 70% of the effect of low molecular weight heparin was neutralized. The neutralizing effect of protamine chloride on the inhibition of factor Xa (clot test) was 95% for conventional heparin and 55% for low molecular weight heparin, whereas the effect of both heparin preparations on the thrombin inhibition could be completely neutralized. We conclude that conventional heparin is neutralized more effectively in vitro by protamine chloride than is the low molecular weight heparin. The findings do not exclude that protamine chloride is able to suppress in vivo bleedings caused by low molecular weight heparin.

Blood Coagulation↗

Effects of an oral antidiabetic drug on the fibrinolytic system of blood in insulin-treated diabetic patients.

Selected variables of the fibrinolytic system were assessed in 23 men with insulin-treated diabetes with no measurable pancreatic beta-cell function. Gliclazide, a second-generation sulphonylurea drug, was administered to the patients over a period of 6 months in daily doses of 160 mg or 240 mg, and blood samples were obtained before, during, and after treatment. Determined by global assays, the drug did not significantly change plasminogen activator activities in euglobulins. Measurements of specific components of the system of fibrinolysis showed a marginal increase during administration of gliclazide of tissue-type plasminogen-activator antigen and prekallikrein activity in plasma, whereas the activities in euglobulins of the intrinsic plasminogen proactivators remained nearly the same during the study. Levels in plasma and euglobulin of C1-inactivator antigen and in plasma of factor XII antigen and t-PA inhibition capacity remained constant throughout the study. There were no changes of the increase in concentration of t-PA activity and t-PA antigen following venous occlusion. The metabolic state remained the same during the whole study. It is concluded that gliclazide induces small, but significant, non-insulin-dependent extrametabolic effects on the extrinsic (t-PA) and intrinsic (prekallikrein) system of fibrinolysis. Whether these changes are of physiological importance remains to be demonstrated.

Administration, Oral↗

Venous thrombosis after abdominal surgery. A comparison between subcutaneous heparin and antithrombotic stockings, or both.

In an open controlled study, 248 consecutive patients (age more than 40 yrs) admitted for major abdominal surgery were randomized to one of three prophylactic antithrombotic treatments. Eighty-five patients received subcutaneous heparin, 74 patients had graduated compression stockings to the knee (TED stockings), and 89 patients had both subcutaneous heparin and stockings. Treatment began on the evening before operation and continued to complete mobilization, or for not less than five days postoperatively. On the fourth or fifth postoperative day, the patients underwent a 99mTc-plasmin test of the lower limbs as a test for deep vein thrombosis. There were 29.7% positive tests in the stocking group, 29.4% in the group with heparin prophylaxis, and 25.8% in the combined group. Differences between treatments were not statistically significant.

Abdomen↗

Depression of tissue plasminogen activator (t-PA) activity and rise of t-PA inhibition and acute phase reactants in blood of patients with acute myocardial infarction (AMI).

We determined during the acute stage of myocardial infarction selected fibrinolysis variables (tissue-type plasminogen activator, intrinsic plasminogen activators, tissue-type plasminogen activator inhibition, C1-inactivator) and related the observed changes to changes in two acute phase reactants (C-reactive protein, fibrinogen). Acute myocardial injury induce significant increases in blood of tissue-type plasminogen activator inhibition (day one, p less than 0.05), C-reactive protein (day three, p less than 0.01), fibrinogen (day six, p less than 0.01), and C1-inactivator (day eight, p less than 0.01). Tissue-type plasminogen activator activity measured as C1-inactivator resistant fibrinolytic activity showed a minimum day two after the acute attack (p less than 0.01), whereas plasminogen activator activities arising from the intrinsic system of fibrinolysis remained constant. The observed changes did not parallel the occurrence of deep vein thrombosis indicated by a positive Tc-plasmin test (41% of the patients).

Acute-Phase Proteins↗

A selective depression of tissue plasminogen activator (t-PA) activity in euglobulins characterises a risk group among survivors of acute myocardial infarction.

Among 29 patients recovering from a first-time acute myocardial infarction (AMI) 9 patients suffered reinfarction during a four year follow-up period. The 9 reinfarction patients were found to belong to a subgroup of 17 patients with a selective depression to near zero of euglobulin t-PA activity. None of the group of 12 patients with marked t-PA activity suffered a relapse. Euglobulin fibrinolytic activity as usually assayed did not distinguish between groups with or without relapse.

Aged↗

On the usefulness of fibrinolysis variables in the characterization of a risk group for myocardial reinfarction.

In a prospective study selected fibrinolysis variables were assessed in plasma samples from 29 consecutive patients recovering a first instance of acute myocardial infarction and the results were correlated with reinfarction during the next four years. Nine patients suffered a reinfarction leaving a group of 20 patients without evidence of relapse. The reinfarction group was characterized by lower tissue plasminogen activator activities in plasma euglobulins (p less than 0.05), significantly higher plasma concentrations of tissue plasminogen activator antigen (p less than 0.002) and a tendency to a higher plasma level of plasminogen activator inhibition capacity. There were no significant differences between the groups in plasma concentrations of plasminogen, histidine-rich glycoprotein, plasminogen kringle-4-binding-protein, and alpha 2-antiplasmin.

Fibrinolysis↗

Characterization of plasminogen activators in unstimulated and stimulated human whole saliva.

The fibrinolytic activity of saliva from healthy males was studied on plasminogen-free and plasminogen-rich fibrin plates. A cell-bound plasminogen activator in human unstimulated and stimulated whole saliva was demonstrated. The assessed fibrinolytic activities could always be quenched by incorporation into the fibrin plates of IgG antibodies raised against human two-chain tissue-plasminogen activator (t-PA), while additional experiments indicated the absence in normal human saliva of urokinase-like and factor XII-dependent plasminogen activators as well as the absence of inhibitors of fibrinolysis. Thus, t-PA is the only type of plasminogen activator in normal human saliva. The present findings seem to support our recent clinical observations of a decrease in the incidence of bleeding complications and need for replacement therapy in hemophiliacs undergoing oral surgery during local antifibrinolytic therapy with tranexamic acid. Whether the findings might also be of importance in other pathological conditions of the oral cavity, such as impaired wound healing, remains to be elucidated.

Factor XII↗

A delaying influence of cryoglobulins in the assessment of euglobulin fibrinolytic activity.

The presence of cryoglobulin in plasma was found to interfere with the assessment of euglobulin fibrinolytic activity. Cryoglobulins co-precipitate with the isoelectrically precipitated euglobulins thereby giving rise to erroneous determinations of components of the extrinsic and intrinsic fibrinolytic systems. Cold-promoted activation of the F XII-dependent part of the intrinsic proactivator system was related to the presence of cryoglobulins. Strictly optimized procedures for the preparation of euglobulin solutions are essential in the accurate determination of euglobulin fibrinolytic activity. Resuspended euglobulins should be kept for at least 30 min at 0 degree C followed by at least 2 min at 37 degrees C in order to secure conditions yielding accurate and reproducible assays of activity in samples of patient plasma.

Chemical Precipitation↗

The autodigestion of human plasmin follows a bimolecular mode of reaction subject to product inhibition.

Plasmin is a labile enzyme destroyed by a process termed autodigestion. Studied by a kinetic assay on the substrate Tos-Gly-Pro-Lys-pNA this process is shown to follow a bimolecular mode of reaction, which is retarded by plasmin degradation products. Plasmin is protected by fibrinogen, by epsilon-aminocaproic acid (6-aminohexanoic acid), by increasing ionic strength, and by glycerol. CNBr fragments of fibrinogen did not protect. Lack of substrate protection of plasmin may give rise to errors in a two-stage plasminogen activator assay, while the presence of substrate in a one-stage method prevents degradation of the generated plasmin.

Aminocaproic Acid↗

Neurophysiological variables and fibrinolysis in insulin-dependent diabetes treated with an aldose reductase inhibitor or placebo. A double-blind randomized study.

In a double-blind study we randomized insulin-dependent diabetics (n = 19) into a group (n = 12) given daily 250 mg Sorbinil, a potent aldose reductase inhibitor reported to ameliorate diabetic neuropathy, and another group (n = 7) given placebo for 1 year. Objective, neurophysiological variables (biothesiometry, electromyography, nyctometri) were followed throughout the study and correlated with fibrinolytic variables in blood. We found that Sorbinil did not improve any of the selected neurophysiological variables. Neither did Sorbinil induce marked changes in the fibrinolytic activities of the extrinsic, tissue-type plasminogen activator (t-PA), or in the intrinsic factor XII-dependent or factor XII-independent (urokinase-like) plasminogen activator systems. We found no effect of Sorbinil on the activity of the fast-reacting inhibitor (PA-I) of plasminogen activator. Levels of PA-I in plasma influence the amounts of t-PA precipitated in euglobulins.

Aldehyde Reductase↗

Distinction by radioisotope technique of a subgroup with increased thrombophilic potential among patients submitted to major abdominal surgery.

Deep vein thrombosis (DVT) detectable by the 99mTechnetium-labeled plasmin test developed in 13 (37%) of 35 sequentially studied patients, all above 40 years, undergoing elective major abdominal surgery. Ten of the 13 patients with DVT had an abnormal pulmonary perfusion scintigram, suggesting pulmonary embolism (PE), but only three had clinical evidence of thrombotic disease.

Abdomen↗

On the significance of antithrombin-III, alpha 2-macroglobulin, alpha 2-antiplasmin, histidine-rich glycoprotein, and protein C in patients with acute myocardial infarction and deep vein thrombosis.

In a longitudinal study the plasma levels of antithrombin-III, alpha 2-macroglobulin, alpha 2-antiplasmin, histidine-rich glycoprotein, and protein C were followed in two groups of patients with acute myocardial infarction (AMI), one with and one without deep vein thrombosis (DVT). None of the sequentially studied periods revealed significant differences between the two groups of patients. However, small but consistently higher levels of histidine-rich glycoprotein in patients with DVT suggested the existence among patients submitted for myocardial infarction of a subgroup with increased thrombophilic potential. It was concluded that the inhibitors studied are of little value as possible indicators of the presence of DVT at early stages of the disease when clinical signs are absent and when antithrombotic prophylaxis should preferably be initiated.

Aged↗

Plasma histidine-rich glycoprotein and plasminogen in patients with liver disease.

Histidine-rich glycoprotein (HRG) has been reported to be a fibrinolysis regulating protein due to its capacity to bind to the high affinity lysine binding sites of plasminogen. Using immunological methods we have measured the concentrations in plasma of HRG and total plasminogen and calculated the amounts of plasminogen not bound to HRG (free plasminogen) in 28 patients with moderate to severe liver disease. All three parametres showed wide individual variations, but with decreasing functional capacity of the liver the individual levels of plasminogen were reduced earlier than those of HRG leading to decreased amounts of free plasminogen. Simultaneous determinations of HRG and total plasminogen combined with a calculation of free plasminogen might yield valuable information when evaluating patients for the availability of plasminogen.

Adult↗

A functional plasminogen assay utilizing the potentiating effect of fibrinogen to correct for the overestimation of plasminogen in pathological plasma samples.

An overestimation of the plasminogen concentration occurs in patients with elevated levels of fibrin degradation products (fdp) and/or fibrinogen, when using assays based on the activation of plasminogen by streptokinase (Sk) followed by the hydrolysis of a synthetic chromogenic substrate. This source of error could be overcome by addition of fibrinogen in excess to the plasminogen assay thereby obtaining maximum stimulation of the Sk-plasminogen complex. The late degradation products of fibrinogen and fibrin, Dcate and Ddimer, respectively, had no potentiating effect on the Sk-plasminogen complex. The modified assay was designed as a manual method or for a centrifugal analyzer. The excellent reproducibility is illustrated by the coefficient of variation (CV) within series being 1.3% (n = 24) and from day to day being 1.9% (n = 20).

Autoanalysis↗