Biomedical subjects
Publications and source records attributed to W Ganz.
Most cases of osteomyelitis of the skull base occur as a result of inadequately treated localized malignant otitis externa. We present four patients with osteomyelitis of the skull base who did not present initially as malignant otitis externa. Increased morbidity may occur when these atypical cases are not promptly recognized and treated.
This study evaluates a new nonangiographic marker of reperfusion--a rapid initial increase in plasma creatine kinase (CK) and CK-MB activity--in 50 patients receiving intracoronary streptokinase. Blood for CK and CK-MB activity was sampled at 30-minute intervals and angiography performed at 15-minute intervals or earlier if there were clinical signs suggestive of reperfusion. An absolute first-hour increase in CK activity of 480 +/- 345 IU/liter (range 54 to 1,440 IU/liter), or a relative first-hour increase of 34 +/- 18% (range 13 to 67% of the peak rise), or an absolute first-hour increase in CK-MB activity of 48 +/- 36 IU/liter (range 10 to 144 IU/liter) or a relative first-hour increase of 27 +/- 13% (range 13 to 57%) was found in patients immediately after reperfusion with Thrombolysis In Myocardial Infarction (TIMI) grade 3 perfusion of the artery of infarction. The onset of rapid increase in CK and CK-MB activity closely reflected the time of angiographic documentation of reperfusion. In contrast, in the absence of reperfusion, the absolute rate of increase in CK activity measured in the last hour of the 2 1/2-hour period beginning with the start of treatment was only 15 +/- 9 IU/liter on the average (range 2 to 30 IU/liter) and the relative rate of rise was 3 +/- 2% on the average (range 1 to 6%).(ABSTRACT TRUNCATED AT 250 WORDS)
Forty-two patients with acute myocardial infarction received 150-mg recombinant human tissue-type plasminogen activator (rt-PA) at 2.3 +/- 1.2 hours after the onset of chest pain. After a 40 U/kg bolus of heparin, rt-PA was given as a 10-mg bolus followed by a 2-hour continuous infusion of 90 mg in the first hour and 50 mg in the second hour. Nonangiographic signs of reperfusion occurred during treatment (41 +/- 21 minutes) in 35 patients and in 1 other patient about 30 minutes after rt-PA. Three patients had discordant nonangiographic signs of reperfusion, 2 patients had no evidence of reperfusion and 1 patient in cardiogenic shock died before completion of the rt-PA infusion and before reperfusion status could be ascertained. Clinical signs of early reocclusion occurred in 4 of the 36 patients with evidence of reperfusion, 3 of whom were retreated with rt-PA with clinical success in 2. Coronary angiography 10 +/- 8 hours later revealed a patent artery of infarction in 35 patients: 32 with nonangiographic signs of sustained reperfusion, both patients with successfully treated reocclusion and 1 of 3 patients with discordant signs of reperfusion. Angiography revealed evidence of partial reperfusion in the remaining 2 patients with discordant signs, and an occluded artery was found in both patients without any evidence of reperfusion and in both patients with clinical signs of persistent reocclusion. Hemorrhagic complications occurred in 9 patients, 7 were related to procedural trauma and 2 patients required a blood transfusion. Four patients died, each of a cardiac cause: 3 in hospital and 1 at home.(ABSTRACT TRUNCATED AT 250 WORDS)
Since thrombi continue to incorporate fibrin during lysis we tested the effect of pretreatment with ancrod, a defibrinating agent from Malaysian pit viper venom, on thrombolysis with urokinase and streptokinase. Thrombi were induced by copper-coils in the carotid arteries of the dogs, weighed after 1 hour and inserted into the femoral arteries of the same animals. They were then exposed for 15 min to iv boluses of streptokinase 10,000 U/kg, urokinase 10,000 U/kg and urokinase 25,000 U/kg with or without pretreatment with ancrod. Ancrod depleted fibrinogen within 5 min and enhanced the lytic effect of streptokinase from 25 +/- 8% to 59 +/- 13% (p less than .05), urokinase 10,000 U/kg from 16 +/- 11% to 66 +/- 18% (p less than .01) and urokinase 25,000 U/kg from 27 +/- 17% to 85 +/- 8% (p less than .001) of the initial thrombus weight. Ancrod itself did not activate plasminogen to plasmin. We conclude that ancrod enhances thrombolysis probably by depleting fibrinogen and preventing new fibrin incorporation into the thrombus during lysis.
The time course and characteristics of ventricular arrhythmias were studied in 45 consecutive patients with acute myocardial infarction who received intravenous streptokinase and underwent 24-hour Holter monitoring both after admission and before discharge 8 +/- 3 days later. In 41 of the 45 patients, thrombolytic treatment resulted in reperfusion as determined by characteristic clinical signs, i.e., rapid relief of pain associated with rapid resolution of ST-segment elevation and simultaneous abrupt increase in serum creatine kinase-MB activity. During the first 24 hours after reperfusion, the prevalence of ventricular premature complexes (VPCs) and couplets was nearly 100%, with an average frequency of 67 VPCs (range 1 to 1,336, median 44) and 6 couplets per hour per patient (range 1 to 97, median 4). Ninety percent of patients had an average of 8 runs of accelerated idioventricular rhythm per hour per patient (range 1 to 226, median 5) and 23% of the patients had an average of 2 runs of ventricular tachycardia per hour per patient (range 1 to 22, median 2) during the first 24 hours after reperfusion. The frequency of arrhythmias began to decrease 8 to 12 hours after reperfusion. Except for VPCs, ventricular arrhythmias were rare during the predischarge Holter study. Arrhythmias after reperfusion did not produce clinical symptoms and did not degenerate into ventricular fibrillation even though the patients were not receiving antiarrhythmic therapy. In the 4 patients without signs of reperfusion, the prevalence and frequency of all ventricular arrhythmias during the 24 hours after treatment was lower than in patients with reperfusion, and none had an accelerated idioventricular rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
The influence of patient age on mortality risk and on the incidence of serious hemorrhagic complications after treatment of acute myocardial infarction (AMI) with intravenous streptokinase (SK) and heparin was examined in 120 consecutive patients. No upper age limit was set for patient inclusion. The mortality rate increased abruptly in patients aged 75 years or older such that the 24 patients in that age group had a 10-fold higher in-hospital mortality rate (33% vs 3%) and 1-year mortality rate (42% vs 4%) than the 96 patients younger than 75 years. This increased mortality rate in the elderly patients was related to a 2-fold higher incidence of major hemorrhagic complications (24% vs 11%) and an increased incidence of anterior AMI, healed prior AMI, multiple-vessel coronary artery disease and extensive myocardial necrosis estimated by peak creatine kinase-MB. Hemorrhagic complications were more frequent in women than in men and in patients with diabetes mellitus or systemic hypertension; all of these conditions were more prevalent in patients aged 75 years and older than in those younger than 75 years. In contrast, the incidence of hemorrhagic complications in nondiabetic elderly men (1 of 12) was similar to the incidence of bleeding in the patients younger than 75 years. Based on our data and those from other studies reporting no reduction in mortality in elderly patients with AMI who are treated with intravenous SK, it is recommended that patients aged 75 years or older should not be routinely treated with intravenous SK.(ABSTRACT TRUNCATED AT 250 WORDS)
The significance of inferior ST segment changes during acute anterior myocardial infarction was studied in 60 patients with acute anterior infarction who had angiographic visualization of the entire distribution of the left anterior descending artery after thrombolytic therapy with streptokinase. In 34 patients (Group 1) this artery supplied the anterior wall of the left ventricle up to or including the apex but did not reach the inferior wall; in 16 patients (Group 2) it continued beyond the apex onto the inferior wall of the left ventricle; and in 10 patients with prior inferior infarction (Group 3) it partially supplied the inferior wall of the left ventricle through collateral channels to an occluded right or dominant circumflex coronary artery. Consistent with this anatomy, evidence of inferior wall ischemia was significantly more frequent in Groups 2 and 3 than in Group 1 by thallium-201 scintigraphy (91 versus 7%) and by contrast left ventriculography (91 versus 13%). There was no difference in the magnitude of precordial ST segment elevation among the three groups but the inferior ST segment depression was significantly smaller in Groups 2 and 3 with concomitant inferior wall ischemia than in Group 1 (aVF: -0.5 +/- 0.7; -0.5 +/- 1.0; -1.8 +/- 0.8 mm, respectively; p less than 0.001) with 10 of the 26 patients in Groups 2 and 3 having an elevated or isoelectric ST segment in aVF compared with none of the 34 patients in Group 1 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Seven of 214 patients (3%) with acute myocardial infarction (120 inferior and 94 anterior) developed atrial fibrillation within 3 hr of the onset of chest pain. All seven patients had an inferior infarction and in all seven the left circumflex artery was occluded proximal to the origin of its left atrial circumflex branch. In five patients this occlusion was acute and was the cause of inferior infarction and in the remaining two patients the occlusion was old and the inferior infarction was due to an acute occlusion of the right coronary artery that also supplied extensive collaterals to the previously occluded left circumflex artery. All seven patients also had impaired perfusion to the atrioventricular nodal artery, as evidenced by total occlusion proximal to its origin or by stenosis proximal to its origin associated with second- or third-degree atrioventricular block. In contrast, early atrial fibrillation did not occur in any of the 18 patients with inferior myocardial infarction due to acute occlusion of the distal left circumflex artery or in any of the five patients with inferior infarction due to acute occlusion of the proximal left circumflex artery if perfusion to the atrioventricular nodal artery was not impaired. Early atrial fibrillation did not occur in any of the 90 patients with inferior infarction due to acute occlusion of the right coronary artery, including 12 patients with occlusion proximal to the sinus nodal artery, but without coexistent occlusion of the left circumflex artery.(ABSTRACT TRUNCATED AT 250 WORDS)
The relation between the level of residual plasma fibrinogen and coronary artery reperfusion after 750,000 IU of intravenous (i.v.) streptokinase (SK) was examined in 76 patients with acute myocardial infarction. Both the frequency and rapidity of reperfusion were greater in the 53 patients in whom the residual fibrinogen level was 50 mg/dl or less (low fibrinogen) than in the 23 patients in whom it was more than 50 mg/dl (high fibrinogen). Reperfusion occurred in all 53 patients in the low-fibrinogen group, compared with only 15 patients in the high-fibrinogen group (p less than 0.001). The interval from initiation of SK to clinical signs of reperfusion was 50 +/- 34 minutes in the low-fibrinogen group and 110 +/- 54 minutes in the high-fibrinogen group (p less than 0.001). A high fibrinogen level occurred in 58% of patients who weighed more than 85 kg and in 25% of patients who weighed 85 kg or less (p less than 0.05). No patient who weighed 60 kg or less had a high fibrinogen level. The high-fibrinogen group also had a greater incidence of a high anti-SK antibody titer: 8 of 13 patients (62%) tested, compared with none of the 8 patients tested in the low-fibrinogen group (p less than 0.01). Our data indicate that a high residual fibrinogen level after administration of i.v. SK identifies patients in whom SK is relatively ineffective, probably because of inadequate dosage of inactivation of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
The potential value of the ratio of precordial ST-segment depression to inferior ST-segment elevation as a sign of concomitant right ventricular (RV) ischemia was examined. The study group consisted of 68 patients, admitted within 3 hours of the onset of inferior acute myocardial infarction (AMI), in whom there was no evidence of prior AMI. In 27 of the 34 patients in whom inferior AMI was the result of right coronary artery occlusion proximal to the RV branch, the magnitude of ST-segment depression in lead V2 was 50% or less of the magnitude of ST-segment elevation in lead aVF, whereas in only 3 of the 34 patients in whom the site of occlusion was either distal to the RV branch (n = 23) or in the left circumflex artery (n = 11) was this ratio 50%; in no patient was it less than 50% (p less than 0.001). All 34 patients with occlusion of the right coronary artery proximal to the RV branch also had regional or global ischemic RV dysfunction by radionuclide ventriculography, with a mean RV ejection fraction of 30 +/- 10% compared with 42 +/- 6% in patients with occlusion distal to the RV branch or in the left circumflex artery (p less than 0.001). In conclusion, in patients with evolving inferior AMI, ST-segment depression in lead V2 of 50% or less of the magnitude of ST-segment elevation in lead aVF may be a useful sign (sensitivity 79%, specificity 91%, positive predictive value 90% and negative predictive value 82%) for identifying patients with concomitant RV ischemia.
In patients treated with streptokinase there is a rapid and significant decrease in the level of fibrinogen in the circulation. In dogs given streptokinase there is no such change in circulating fibrinogen. To find an explanation for this species difference in response to streptokinase, the inhibition of SK-human plasmin and SK-dog plasmin by soybean trypsin inhibitor, alpha 2-antiplasmin and alpha2-macroglobulin were compared in this study. Soybean trypsin inhibitor completely blocked the hydrolysis of S-2251 substrate (D-val-L-leu-lys-p-nitroanilide) by SK-dog plasmin and had no effect on SK-human plasmin. Alpha 2-Antiplasmin, the physiologically important regulator of fibrinolysis, inhibited S-2251 hydrolysis by SK-dog plasmin but not the activity of SK-human plasmin. alpha 2-Macroglobulin showed 100% inhibition of proteolytic activity and 50% inhibition of S-2251 activity of SK-dog plasmin, and had no effect on SK-human plasmin. Studies with fresh human and dog plasma also showed that the SK-dog plasmin is rapidly inactivated by the alpha 2-antiplasmin present in the plasma. The inactivation of SK-dog plasmin and not SK-human plasmin by plasma inhibitors explains the differences in the response of dog and humans to the administration of streptokinase.
D dimer, a degradation product of cross-linked fibrin, is generated by lysis of fibrin but not by lysis of fibrinogen and can be reliably detected by specific monoclonal antibody techniques. The generation of D dimer after intravenous streptokinase in acute myocardial infarction was studied with the use of a semiquantitative latex agglutination immunoassay. This assay utilizes the monoclonal antibody DD-3B6/22, raised by conventional hybridoma technology, against a highly purified preparation of human D dimer and is adjusted to give a positive agglutination at a D dimer serum concentration of greater than 200 ng/ml (upper limit of normal). Twenty-one patients with acute transmural myocardial infarction of less than 3 hours' duration were studied. Fifteen patients received 0.75 to 1.5 million U intravenous streptokinase and 6 patients were treated conventionally without thrombolytic therapy. An elevated serum level of D dimer was detected before treatment in only 1 of 15 patients receiving intravenous streptokinase and within 2 hours of treatment in the remaining 14 patients who received streptokinase. In contrast, an elevated serum D dimer level was not detected during the first 24 hours in any of the six conventionally treated patients, including two patients who manifested the clinical syndrome of spontaneous reperfusion. The data suggest that in patients with acute myocardial infarction, an elevated serum level of D dimer, a cross-linked fibrin degradation product occurs early after administration of a large dose of streptokinase, but is infrequent during the first 24 hours in conventionally treated patients with acute infarction. Measurement of D dimer may be potentially useful for monitoring thrombolysis in patients with acute myocardial infarction.
The pattern of reverse redistribution on the day 10 poststreptokinase resting thallium-201 myocardial scintigrams is a common finding in patients who have undergone streptokinase therapy in evolving myocardial infarction. To investigate this phenomenon, 67 patients who underwent streptokinase therapy were studied pre- and 10 days poststreptokinase therapy resting thallium-201 studies, poststreptokinase therapy resting radionuclide ventriculography and coronary arteriography (60 of the 67 patients). Of the 67 patients, 50 (75%) showed the reverse redistribution pattern on the day 10 thallium-201 study (Group I), 9 (13%) had a nonreversible defect (Group II) and the remaining 8 (12%) had a normal study or showed a reversible defect (Group III). The reverse redistribution pattern was associated with patency of the infarct-related artery (100%), quantitative improvement in resting thallium-201 defect size from day 1 to day 10 study (94%) and normal or near normal wall motion on day 10 radionuclide ventriculography (80% of segments with marked and 54% of those with mild reverse redistribution). In contrast, nonreversible defects were associated with significantly less frequent patency of the infarct-related artery (67%, p = 0.01), improvement in defect size (11%, p less than 0.001) and normal or near normal wall motion (21%, p less than 0.05). Group III patients were similar to Group I with respect to these variables. The quantitated thallium-201 percent washout was higher in the regions with the reverse redistribution pattern (49 +/- 15%) compared with the contralateral normal zone (24 +/- 15%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effect of pretreatment with heparin on lysis of arterial thrombi by tissue-type plasminogen activator (rt-PA) was studied in 19 dogs. Copper coil-induced carotid artery thrombi were weighed, inserted into the femoral arteries, and exposed to a 15 min infusion of rt-PA at 10 micrograms/kg/min either with (n = 6 thrombi) or without pretreatment with a 200 unit/kg bolus of heparin (n = 6 thrombi). The infusion of rt-PA without pretreatment reduced the thrombus weight by 27.6 +/- 7.4%, while infusion of rt-PA with pretreatment reduced it by 79.1 +/- 12.3% (p less than .0001). To test the hypothesis that heparin enhanced thrombolysis by preventing continued incorporation of new fibrin into the thrombus during thrombolysis we repeated the experiments using pretreatment with 8 U/kg of ancrod, which rapidly depletes fibrinogen. Pretreatment with ancrod (n = 6 thrombi) depleted fibrinogen and enhanced the lytic effect of rt-PA to a similar degree as pretreatment with heparin, resulting in a 67.6 +/- 12.3% (NS) decrease in thrombus weight. We conclude that heparin significantly enhances the thrombolytic effect of rt-PA, probably by preventing new fibrin formation and its incorporation into the thrombus during lysis.
Explore the source record for details and available documents.