Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

rDSPA alpha 1 (recombinant Desmodus salivary plasminogen activator alpha 1) is a recombinant protein corresponding to a natural plasminogen activator from the vampire bat Desmodus rotundus. The thrombolytic properties of rDSPA alpha 1 and tissue-type plasminogen activator (t-PA) were compared in a rat model of pulmonary embolism. Whole blood clots, produced in vitro and labeled with 125I-fibrinogen, were embolized into the lungs of anesthetized rats. Thrombolysis was calculated from the difference between initial clot radioactivity and that remaining in the lungs at 60 minutes. Blood was sampled for gamma counting, measurement of hemostatic factors, and plasminogen activator antigen levels. Thrombolysis at 3, 10, 30, and 100 nmol/kg intravenously (10% bolus, 90% over 60 minutes) amounted to 30% +/- 2%, 51% +/- 4%, 85% +/- 4%, 98% +/- 0% for rDSPA alpha 1 and 30% +/- 3%, 41% +/- 3%, 57% +/- 6%, 93% +/- 2% for t-PA (controls: 29% +/- 2%; mean +/- SEM, n greater than or equal to 6). t-PA at 100 nmol/kg significantly decreased fibrinogen, plasminogen, and alpha 2-antiplasmin levels by 33% +/- 7%, 38% +/- 8%, and 61% +/- 9%, whereas rDSPA alpha 1 at 100 nmol/kg only lowered alpha 2-antiplasmin significantly (by 29% +/- 6%). Compared with t-PA, rDSPA alpha 1 is the more potent and more clot selective (fibrin specific) thrombolytic agent. These results suggest that rDSPA alpha 1 may be safer and more efficacious than currently used thrombolytics.
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PMID:Thrombolytic properties of Desmodus rotundus (vampire bat) salivary plasminogen activator in experimental pulmonary embolism in rats. 153 47

A pulmonary embolism model in hamsters was used for the quantitative evaluation of the thrombolytic and pharmacokinetic properties of variants of tissue-type plasminogen activator (t-PA). A 25 microliters 125I-fibrin labeled human plasma clot was made in vitro and injected into the jugular vein of heparinized hamsters. The extent of thrombolysis within 90 min was determined as the difference between the radioactivity injected in the jugular vein and that recovered in the heart and lungs. Recombinant t-PA (home-made rt-PA or Activase) infused intravenously over 60 min caused dose-dependent progressive thrombolysis. The results of thrombolytic potency (clot lysis in percent versus dose administered in mg/kg) and of specific thrombolytic activity (clot lysis in percent versus steady state plasma level in microgram/ml) were fitted with an exponentially transformed sigmoidal function y = 100 c/(1 + e-a(ax-eh] and the maximal percent lysis (c), the dose or plasma level at which maximal rate of lysis is achieved (b) and the maximal rate of lysis (z = 1/4 ac.eb) were determined. With rt-PA, these parameters were c = 72 +/- 6% (mean +/- SEM), b = 0.19 +/- 0.08 mg/kg, z = 68 +/- 25% lysis per mg/kg, with corresponding values of 87 +/- 5%, 0.07 +/- 0.03 mg/kg and 150 +/- 38% lysis per mg/kg for Activase (p = NS). Deletion of the finger and growth factor domains in rt-PA (rt-PA-delta FE) was not associated with marked alteration of the thrombolytic potency (c = 90 +/- 30%, b = 0.34 +/- 0.35 mg/kg, and z = 54 +/- 14% per mg/kg), but was associated with a significant reduction of the specific thrombolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolytic and pharmacokinetic properties of human tissue-type plasminogen activator variants, obtained by deletion and/or duplication of structural/functional domains, in a hamster pulmonary embolism model. 190 70

We performed a double-blind randomized trial comparing high doses of subcutaneous heparin (12,500 units every 12 hours) with low doses (5000 units every 12 hours) for 10 days in the prevention of left ventricular mural thrombosis in 221 patients with acute anterior myocardial infarction. Left ventricular mural thrombosis was observed by two-dimensional echocardiography on the 10th day after infarction in 10 of 95 patients (11 percent) in the high-dose group and in 28 of 88 patients (32 percent) in the low-dose group (P = 0.0004). One patient in the high-dose group and four in the low-dose group had nonhemorrhagic strokes (P = 0.17). One patient in the low-dose group had a fatal pulmonary embolism. There was no difference in the frequency of hemorrhagic complications, which occurred in six patients in the high-dose group and four in the low-dose group. The mean (+/- SEM) plasma heparin concentration was 0.18 +/- 0.017 U per milliliter in the high-dose group and 0.01 +/- 0.005 U per milliliter in the low-dose group (P less than 0.0001). In the high-dose group, the mean plasma heparin concentration was 0.10 +/- 0.029 U per milliliter among patients with abnormal two-dimensional echocardiograms, as compared with 0.19 +/- 0.019 U per milliliter among patients with normal echocardiograms (P = 0.01). We conclude that heparin administered subcutaneously in a dosage of 12,500 units every 12 hours to patients with acute anterior transmural myocardial infarction is more effective than a lower dosage (5000 units every 12 hours) in preventing left ventricular mural thrombosis.
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PMID:Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction. 274 63

To quantify physician practices in the care of patients with presumed pulmonary embolism or deep venous thrombosis, we analyzed heparin sodium orders, the intensity of anticoagulation, and complications in 65 patients with the diagnosis of deep venous thrombosis or pulmonary embolism. All patients were given heparin, for a mean (+/- SEM) period of 8.8 +/- 0.4 days. A high percentage of patients (60%) did not have a single partial thromboplastin time (PTT) greater than 1.5 times control within the first 24 hours of heparin therapy. Not until day 8 were 90% of PTTs in therapeutic range. We identified five common practices that led to delays in achieving a PTT greater than 1.5 times the laboratory control: (1) failure to start heparin therapy at the time of initial clinical suspicion, (2) choice of a heparin sodium bolus (mean, 5861 +/- 365 U) and continuous infusion (1026 +/- 148 U/h) insufficient to elevate the PTT to greater than 1.5 times control, (3) delay in obtaining the first PTT (mean, 11.7 +/- 1 h after start of heparin therapy), (4) insufficient heparin dosing in response to a low PTT, and (5) excessive and prolonged reductions in heparin therapy in response to a PTT greater than three times control, leading to subtherapeutic levels in 56% of subsequent PTTs. We think that poor understanding of heparin kinetics, overcautious behavior of physicians, and high heparin requirements in this selected population account for the findings.
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PMID:Physician practices in the treatment of pulmonary embolism and deep venous thrombosis. 337 15

Endoscopic sphincterotomy (ES) was attempted in 409 patients with common bile duct stone(s) (CBDS). The mean age of patients was 72.0 +/- 0.8 years (m +/- SEM); 47 p. 100 presented risk factors; 57 p.100 had previously been cholecystectomized while 43 p. 100 had not. On an average, patients in the former group were older (80 +/- 0.7 years) than in the latter 65.4 +/- 1.0 years, p less than 0.001). The procedure was successful in 98 p. 100 of the patients, after a standard ES in 78.5 p. 100 or after different technical artifices in 21.5 p. 100. The vacuity of the CBD was obtained in 96.5 p. 100 of the cases. During the first month after the ES, 13 p. 100 of the patients had complications and 4 p. 100 died; 37 complications (9 p. 100) were related to the ES and were responsible for death in 4 patients: 18 episodes of bleeding at the site of ES, 7 acute pancreatitis, 6 cholangitis, 4 retroperitoneal perforations and 2 other complications. The occurrence of these complications was closely related to the technique of ES being more frequent after technical artifices than after a standard ES (p less than 0.001). On the other hand, these complications occurred independently of the age of patients or of previous cholecystectomy. Seventeen complications (4 p. 100) did not depend directly on ES and were responsible for death in 14 patients (3 p. 100): pneumopathy, pulmonary embolism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Results of endoscopic sphincterotomy in common bile duct lithiasis]. 397 27

To evaluate the effects of the short-term, high-dose sodium heparin therapy on biochemical markers of bone metabolism, we studied 20 patients (11 males and 9 females) with pulmonary embolism, treated with sodium heparin (daily dose range: 40,000-45,000 I.U. by continuous i.v. infusion). Heparin therapy lasted 5-7 days, after which patients received warfarin over 12 months. Eleven patients (6 males and 5 females) with ischaemic stroke, treated with i.v. glycerol and pentoxifilline, were used as controls. Before and after therapy serum and urinary markers of bone metabolism were evaluated; in 12 heparin-treated pts., the parameters were also evaluated 4 months after discontinuation of warfarin therapy. After heparin therapy a significant reduction vs. basal value was observed in levels of serum osteocalcin (ng/ml;mean + SEM): 3.32 & 0.19 vs. 2.05 + 0.21; p < 0.001. In the 12 patients evaluated 4 months after discontinuation of warfarin therapy, serum osteocalcin levels returned to basal value: 3.41 + 0.12 ng/ml (p:n.s.). No significant changes of the examined parameters were observed in controls. In conclusion, our data seem to indicate an effect of i.v. short-term heparin therapy on bone metabolism. This effect seems to be characterized by an inhibition of osteoblast function as suggested by the reduction of serum osteocalcin levels.
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PMID:Effects of short-term, high dose, heparin therapy on biochemical markers of bone metabolism. 860 85

The objective of this study was to compare the therapeutic benefit of thrombolytic therapy in women and men with acute pulmonary embolism. Data were combined from five prospective multicenter trials studying the efficacy and safety of pulmonary embolism thrombolysis. The study was conducted in 34 tertiary care medical centers in the United States, Canada, and Italy. Three hundred and twelve patients (144 women and 168 men) diagnosed with pulmonary embolism by either pulmonary angiography or a combination of high-probability ventilation-perfusion scanning and high clinical suspicion with no contraindications to thrombolytic therapy were included. A thrombolytic agent (either tissue plasminogen activator or urokinase) followed by intravenous heparin was administered. The magnitude of improvement on follow-up ventilation-perfusion scans and pulmonary angiograms and the frequency of important bleeding episodes were measured. The degree of reperfusion with thrombolysis as measured by lung perfusion scanning (mean +/- SEM, 11 +/- 1% in women vs. 12 +/- 1% in men, P = 0.67), improvement in angiographic scores (1.46 +/- 0.17 vs. 1.51 +/- 0.16, P = 0.85), and decrease in mean pulmonary arterial pressures (1.8 +/- 1.0 mmHG vs. 1.3 +/- 0.7 mmHG, P = 0.70) demonstrated little difference between the two genders. In addition, the occurrence of important bleeding was similar in women and men (17% vs. 22%, P = 0.23). In conclusion, the benefits and risks posed by thrombolysis for pulmonary embolism are similar in magnitude for women and men. Therefore, patient gender should not influence the decision to treat pulmonary embolism patients with thrombolytic agents.
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PMID:Similarity in Presentation and Response to Thrombolysis Among Women and Men with Pulmonary Embolism. 1076 2

The clinical importance of upper extremity deep venous thrombosis (UEDVT) has been increasingly demonstrated in recent literature. Not only has the risk of pulmonary embolism from isolated upper extremity DVT been demonstrated, but a significant associated mortality has been encountered. Examination of this group of patients has demonstrated the existence of combined upper and lower extremity deep venous thrombosis (DVT) in some patients who exhibit an even higher associated mortality. As a result of this information, it has become the standard practice at this institution to search for lower extremity DVTs in patients found to have acute thrombosis of upper extremity veins. Since January 1999, there have been a total of 227 patients diagnosed with acute UEDVT. Within this group, 211 (93%) patients had lower extremity studies; 45 of these 211 (21%) had acute lower extremity DVTs by duplex examination in addition to the upper extremity DVTs. Overall, there were 145 women, 66 men, and the average age was 70 +/-1.2 (SEM); 22 of these patients had bilateral lower extremity thrombosis (LEDVT), and 8 patients were found to have chronic thrombosis of lower extremity veins. Of the patients with bilateral upper extremity DVTs, there were 3 with bilateral LE acute DVTs. Finally, 8 of the remaining 166 patients (5%) with originally negative lower extremity studies were found to develop a thrombosis at a later date. These data serve to confirm previous studies, on a larger scale, that there should be a high index of suspicion in patients with UEDVT of a coexistent LEDVT.
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PMID:Prospective evaluation of combined upper and lower extremity DVT. 1659 61

A 42-year-old woman died from massive barium sulfate (BaSO(4)) lung embolism after a balloon catheter intended for elective colonography was inserted into her vagina. The vaginal insertion of the balloon catheter caused a bilateral laceration of the vaginal wall which was followed by penetration of BaSO(4) into the afferent veins and massive pulmonary embolism. Fluoroscopy performed during the fatal events and post-mortem X-rays revealed a radio-opaque substance in the vagina and uterus, the pelvic vessels and the vena cava, the right heart chambers, the lungs, and the kidneys. In addition to lungs, finely granular intravascular particles were demonstrated histologically in several organs including the brain and the glomerular capillaries. Scanning (SEM) and transmission (TEM) electron microscopy together with X-ray microanalysis, and inductively coupled plasma atomic emission spectrometry (ICP-AES) allowed the definite identification of BaSO(4) in lungs and confirmed its capacity to penetrate the pulmonary filter and to embolise via the systemic circulation in various organs.
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PMID:Fatal iatrogenic BaSO4 embolism: morphological and ultrastructural findings confirmed by X-ray microanalysis and ICP-AES. 1727 39