Measurement of the lymphatic clearance of the human skin using a fluorescent tracer

The lymphatic clearance of the human skin at the instep of the foot was measured in 20 healthy volunteers (mean age +/- SD 33.8 +/- 10.5 years). Ten microliters of fluorescein isothiocyanate-dextran 150,000 were injected intradermally and the fluorescent light intensity of the deposit was measured 10 min and 24 h after injection by window densitometry. Fluorescent light intensity decreased by 31.2 +/- 13.5 arbitrary units (p < 0.0001) or by a factor of 4.1 +/- 3.9. Reproducibility was tested 2-6 weeks later in 7 subjects and an intraclass reliability of 0.76 was found. These are the first measurements of the lymphatic clearance of the human skin using a fluorescent tracer. The method is easier and safer than the isotope clearance technique and small areas of the human skin can be investigated. The data found form a basis with which to compare measurements made in patients with different forms of edema.     

Combined liver vein and spleen pulp pressure measurements in patients with portal or splenic vein thrombosis

BACKGROUND: Patients with thrombosis of the portal or splenic vein may develop portal hypertension with bleeding from oesophageal or gastric varices. The relevant portal pressure cannot be measured by liver vein catheterization or transhepatic puncture of the portal vein because the obstruction is peripheral to the accessible part of the portal system. METHODS: Liver vein catheterization was combined with percutaneous splenic pressure measurement in 10 patients with portal or splenic vein thrombosis and no cirrhosis, and 10 cirrhotic patients without thrombosis. The splenic pressure was measured by percutaneous puncture below the curvature of the ribs with an angle of the needle to skin of 30 degrees in order to minimize the risk of cutting the spleen if the patient took a deep breath. RESULTS: None of the patients in whom the described procedure was followed had complications. Pressure measurements in the spleen pulp and splenic vein were concordant. The pressure gradient across the portal venous system (splenic-to-wedged hepatic vein pressure) was -1.3 to 8.5 mmHg (median, 2.8 mmHg) in cirrhosis patients and 0-44 mmHg (median, 18 mmHg) in thrombosis patients, the variation reflecting various degrees of obstruction to flow in the portal venous system. Peripheral portal pressure (splenic-to-free liver vein pressure gradient) was 1.1-28 mmHg (median, 17 mmHg) in cirrhotic patients and 11-52 mmHg (median, 23 mmHg) in thrombosis patients. CONCLUSIONS: Liver vein catheterization combined with percutaneous splenic pressure measurement is feasible in quantifying pressure gradient across a thrombosis of the portal/splenic vein and in quantifying portal pressure peripheral to this kind of thrombosis.     

The endogenous thrombin potential and high levels of coagulation factor VIII, factor IX and factor XI.

High plasma concentrations of factor VIII, factor IX and factor XI have been reported as thrombosis risk factors. Using the thrombin generation test in platelet-poor plasma, it was aimed to describe the mechanism for this increased thrombosis risk. Endogenous thrombin potential was measured in platelet-poor plasma in 180 patients with a history of thromboembolism, and results were compared with those of 180 age-matched and sex-matched controls. Subjects with major hereditary and acquired thrombophilia were excluded. Plasma concentrations of the clotting factor VIII, factor IX and factor XI were significantly elevated in patients compared with controls. The mean endogenous thrombin potential was significantly higher in patients than in controls: 191.3 +/- 3.1 (95% confidence interval, 185.3-197.4) arbitrary units versus 180.8 +/- 2.6 (95% confidence interval, 175.7-185.9) arbitrary units (P = 0.009). The endogenous thrombin potential was significantly higher in patients with elevated factor IX and factor XI, but elevated factor VIII was not associated with a significant increase in endogenous thrombin potential. In conclusion, the increased thrombosis risk associated with high plasma concentrations of factor IX and factor XI may be explained by the increase in endogenous thrombin potential. However, this did not help explain the association between elevated factor VIII and thrombosis risk.     

Orgaran in the prevention of deep vein thrombosis in stroke patients.

Venous thrombo-embolism is a common complication in patients with acute ischaemic stroke. Without prophylaxis, deep vein thrombosis occurs in 60-75% of patients with dense hemiplegia, usually in the paralyzed limb, and 1-2% suffer fatal pulmonary embolism. Orgaran (Org 10172, low-molecular-weight heparinoid) has been evaluated for the prevention of deep vein thrombosis in patients with acute ischaemic stroke in two studies. In a double-blind study, 75 patients were randomized to receive Orgaran (50 patients) in a loading dose of 1,000 anti-Xa units intravenously followed by 750 anti-Xa units subcutaneously 12-hourly or placebo (25 patients). Deep vein thrombosis occurred in 2 of 50 (4%) in the Orgaran group and 7 of 25 (28%) in the placebo group (p = 0.005). The corresponding rates for proximal deep vein thrombosis were 0 and 16%, respectively (p = 0.01). There was one major haemorrhage in the treated group and one minor haemorrhage in the placebo group. In the second study, the safety and efficacy of Orgaran was compared with unfractionated heparin in the prevention of deep vein thrombosis in a double-blind randomized trial. Eighty-seven patients with marked lower limb paralysis secondary to stroke were randomized to receive Orgaran (45 patients) in a dose of 750 anti-factor Xa units subcutaneously 12-hourly or unfractionated heparin (42 patients) in a dose of 5,000 units subcutaneously 12-hourly. Venous thrombosis occurred in 4 of 45 (8.9%) of the Orgaran group and 13 of 42 (31%) in the unfractionated heparin group (2p = 0.014). The corresponding rates for proximal vein thrombosis were 4.4 and 11.9%, respectively (2p = 0.255).(ABSTRACT TRUNCATED AT 250 WORDS)     

Whole blood coagulation assessment using rotation thrombelastogram thromboelastometry in patients with acute deep vein thrombosis

Common tests for the assessment of blood coagulation in the acute phase of deep vein thrombosis are of limited value for the evaluation of the associated hypercoagulability. The new rotation thromboelastometry by rotation thrombelastogram has the potential to provide information on whole blood clot formation and prothrombotic state in patients with acute deep vein thrombosis. Rotation thrombelastogram parameters were evaluated in whole blood of 30 patients with a first episode of acute deep vein thrombosis and 40 healthy controls. The effect of factor VIII and fibrinogen levels on rotation thrombelastogram assays was also assessed in the study population and in a model of blood supplemented by increasing amounts of fibrinogen. All assays performed were consistent with a remarkable hypercoagulable profile in deep vein thrombosis patients as compared with controls. In particular, maximum clot firmness and the area under curve values, which are expected to better correlate with the hypercoagulable state in the acute phase of deep vein thrombosis, were significantly higher in patients than in controls. As expected, fibrinogen was shown to be one of the main determinants of the hypercoagulability in rotation thrombelastogram assays. In a small subset of acute deep vein thrombosis patients, inherited thrombophilia had no influence on rotation thrombelastogram parameters. The new rotation thrombelastogram thromboelastometry is a useful tool to detect acute deep vein thrombosis-related hypercoagulability. Prospective studies are needed to define the potential applications of rotation thrombelastogram in the management of deep vein thrombosis patients.     

Blood-borne collagenous debris complexes with plasma fibronectin after thermal injury

Plasma fibronectin augments the clearance of blood-borne foreign and effete complexes by mononuclear phagocytes. The release of a "gelatin-like" ligand into plasma after thermal injury has been reported. We quantified the release of this collagenous debris from thermally injured skin, and its potential interaction with soluble fibronectin in plasma using anesthetized rats. Collagen-like material debris in the plasma was detected by assay of hydroxyproline. Fibronectin was measured by a double antibody enzyme-linked immunosorbent assay (ELISA) technique. Over a 24-hour postburn interval, plasma hydroxyproline increased from 6.7 +/- 0.6 micrograms/mL to a maximum of 19.0 +/- 3.3 micrograms/mL at 60 minutes postburn, and normalized by 6 hours. A direct correlation existed between the magnitude of burn injury and the increase in plasma hydroxyproline. In parallel, plasma fibronectin declined over a 15-minute to 2-hour period postburn, and normalized by 3 to 4 hours with rebound hyperfibronectinemia observed at 24 hours. The elevation in total plasma hydroxyproline was not due to an increase in plasma Clq (zero time, 26.2 +/- 1.4 micrograms/mL; 60 minutes, 23.9 +/- 1.1 micrograms/mL). Tracer studies with 125I-fibronectin showed that the acute decline of plasma fibronectin was due to its uptake by the liver and binding to sites of tissue injury. Total hydroxyproline in extracts of burn skin, used as an index of soluble collagenous material, rose from 15 +/- 3.3 micrograms/g skin at zero time to 129.3 +/- 43.7 micrograms/g skin by 5 minutes postburn, with a decline to 38 +/- 22 micrograms/g skin by 24 hours. The formation of circulating fibronectin-gelatin complexes in vivo was documented by cross-immunoelectrophoresis coupled with autoradiography using 125I-gelatin as a model ligand. Thus, collagenous tissue debris from burned skin may enter the plasma after thermal injury and directly complexes with soluble fibronectin before hepatic phagocytic clearance.     

Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study

BACKGROUND: Up to one third of patients who undergo total knee replacement develop deep vein thrombosis after surgery despite receiving low-molecular-weight heparin prophylaxis. Ximelagatran is a novel direct inhibitor of free and clot-bound thrombin. METHODS: We performed a randomized, parallel, dose-finding study of 600 adults undergoing elective total knee replacement at 68 North American hospitals to determine the optimum dose of ximelagatran to use as prophylaxis against venous thromboembolism after total knee replacement. Patients received either ximelagatran twice daily by mouth in blinded fixed doses of 8, 12, 18, or 24 mg or open-label enoxaparin sodium, 30 mg, subcutaneously twice daily, starting 12 to 24 hours after surgery and continuing for 6 to 12 days. We measured the 6- to 12-day cumulative incidence of symptomatic or venographic deep vein thrombosis, symptomatic pulmonary embolism, and bleeding. RESULTS: A total of 594 patients received at least 1 dose of the study drug; 443 patients were evaluable for efficacy. Rates of overall venous thromboembolism (and proximal deep vein thrombosis or pulmonary embolism) for the 8-, 12-, 18-, and 24-mg doses of ximelagatran were 27% (6.6%), 19.8% (2.0%), 28.7% (5.8%), and 15.8% (3.2%), respectively. Rates of overall venous thromboembolism (22.7%) and proximal deep vein thrombosis or pulmonary embolism (3.1%) for enoxaparin did not differ significantly compared with 24-mg ximelagatran (overall difference, -6.9%; 95% confidence interval, -18.0% to 4.2%; P=.3). There was no major bleeding with administration of 24 mg of ximelagatran twice daily. CONCLUSION: Fixed-dose, unmonitored ximelagatran, 24 mg twice daily, given after surgery appears to be safe and effective oral prophylaxis against venous thromboembolism after total knee replacement.     

Very long-term outcome of 68 vena cava filters percutaneously implanted

Between January 1987 and December 1991, 68 consecutive patients aged 71.5 +/- 12.0 years underwent percutaneous implantation of a vena caval filter, mainly the LGM (N = 64). Fifty seven patients had pulmonary embolism, 61 had deep vein thrombosis of the lower limbs. The average follow-up interval was 4.9 +/- 3.3 years (7.0 +/- 2.7 years for the patients still alive). The follow-up included a telephonic enquiry to determine the date and cause of death, recurrent deep vein thrombosis and/or pulmonary embolism; surviving patients underwent clinical examination, plain abdominal X-ray with a lateral decubitus view and duplex ultrasonography of the lower limb veins to assess the patency of the filter. Fifty three per cent of the patients died. Four predictive factors for mortality were identified: a contra-indication to anticoagulant therapy, chronic post-embolic cor pulmonale, an indication of prophylactic implantation in the elderly and the presence of underlying malignant disease. There were 5.8% recurrences of pulmonary embolism, 26.1% of lower limb deep vein thrombosis and 25% of filter thrombosis. The only predictive factor of thrombosis was a proximal venous thrombus and was associated in 50% of filter thrombosis. Seventy per cent of the plain abdominal X-rays were abnormal with 9 displacements. 9 migrations and 10 closures of the filters. There was a significant correlation between closure on plain abdominal X-ray and caval thrombosis and between recurrent deep vein thrombosis and caval thrombosis. The frequency of long-term complications after implantation of a caval filter in this study suggests that interruption of the vena cava should be reserved for the only validated indications in the presence of a formal contra-indication to or failure of anticoagulant therapy. Other indications require evaluation with prospective randomised trials.     

A low-molecular-weight heparinoid compared with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. A randomized, double-blind study.

OBJECTIVE: To compare the relative safety and efficacy of a low-molecular-weight heparinoid (ORG 10172) with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. DESIGN: Double-blind randomized trial. SETTING: Seven Canadian university-affiliated hospitals. PARTICIPANTS: Eighty-seven patients with acute ischemic stroke resulting in lower-limb paresis. INTERVENTION: Patients received either low-molecular-weight heparinoid, 750 anti-factor Xa units twice daily, or unfractionated heparin, 5000 units subcutaneously twice daily. Treatment was continued for 14 days or until hospital discharge if sooner. MEASUREMENTS: Deep vein thrombosis was diagnosed using 125I-labeled fibrinogen leg scanning and impedance plethysmography. Venography was indicated if either test was positive. Overt hemorrhage, major or minor, was assessed clinically. RESULTS: Venous thrombosis occurred in four patients (9%) given low-molecular-weight heparinoid and in 13 patients (31%) given heparin (relative risk reduction, 71%; 95% CI, 16% to 93%. The corresponding rates for proximal vein thrombosis were 4% and 12%, respectively (relative risk reduction, 63%; P greater than 0.2). The incidence of hemorrhage was 2% in both groups. CONCLUSION: Low-molecular-weight heparinoid, given in a fixed dose of 750 anti-factor Xa units subcutaneously twice daily, is more effective than subcutaneous low-dose heparin for the prevention of deep vein thrombosis in patients with acute ischemic stroke.     

Pulmonary artery wedge pressure and extravascular lung water in patients with acute cardiogenic pulmonary edema requiring mechanical ventilation

This study describe the values of pulmonary artery wedge pressure (PAWP) and the extravascular lung water (EVLW) index in patients with acute cardiogenic pulmonary edema who require mechanical ventilation. Ten consecutive patients with acute cardiogenic pulmonary edema who required mechanical ventilation were studied. Cardiac index was determined with thermodilution. Central venous pressure and PAWP were measured with a pulmonary artery catheter. EVLW index was determined with the thermal dye dilution technique, using a commercially available computer system. Measurements were made at regular preset intervals after the initiation of mechanical ventilation. PAWP was normal at baseline (11.6+/-0.9 mm Hg, range 8 to 17) and did not change. EVLW index was elevated at baseline (13.7+/-1.5 ml/ kg) and decreased to a normal value after 24 hours (8.6+/-1.2 ml/kg, p = 0.02). Concomitantly cardiac index increased from 2.61+/-0.24 to 3.61+/-0.14 L/min/m2 (p = 0.05). There was no correlation between PAWP and EVLW index. Fluid balance was +1,221+/-908 ml after 24 hours and there was a weight gain of 0.88+/-1.06 kg after 24 hours. Thus, patients with acute cardiogenic pulmonary edema requiring mechanical ventilation may have a normal PAWP after mechanical ventilation has been initiated. In a hemodynamic unstable situation, these patients may require fluid challenges to improve cardiac output, despite the presence of pulmonary edema. The pulmonary edema, measured as EVLW index, resolves rapidly when cardiac performance improves, despite positive fluid balances and weight gain in the first 24 hours.     

Generalized alterations in the biomechanical properties of large veins in non-thrombotic thrombophilic young patients.

AIM: In young, post-thrombotic patients, venous distensibility is decreased not only in the affected lower limb, but also in the contralateral limb and in the jugular vein when compared to age-matched control subjects. In the present study, we investigated venous wall mechanical properties in young, asymptomatic thrombophilic patients. METHODS: Eleven young (24+/-0.4 years) control subjects and 9 age-matched patients (21.1+/-1.8 years) with proven thrombophilic molecular defects, but without any signs or history of previous deep vein thrombosis, were compared. Anterolateral and mediolateral diameters of the common femoral, axillary and internal jugular veins were measured by ultrasonography in situ. Pressure alterations were induced by altering body positions and by pressure-controlled Valsalva tests. Distensibility was calculated from diameter and pressure changes. RESULTS: In thrombophilic patients, resting diameter of both the common femoral and of internal jugular veins at low transmural pressure was larger than those for the control subjects. Distensibility, however, was significantly less when high pressures were applied. Alterations in diameter of the axillary vein were minimal. CONCLUSION: Our measurements suggest that there are generalized changes in venous mechanical properties in thrombophilic patients even before the appearance of thrombotic processes. These biomechanical alterations of the venous wall and/or surrounding connective tissue are similar to those found in connection with aging and in post-thrombotic patients. The pathological mechanisms behind these processes are unknown.     

Postoperative portal vein thrombosis in patients with hepatosplenic mansonic schistosomiasis: relationship with intraoperative portal pressure and flow. A prospective study

BACKGROUND/AIMS: Portal vein thrombosis is a frequent postoperative complication after esophagogastric devascularization with splenectomy. The aim of this study was to analyze biochemical, hematological, coagulation blood tests and intraoperative portal vein hemodynamics after surgical treatment of hepatosplenic Mansonic schistosomal portal hypertension. METHODOLOGY: Forty patients with hepatosplenic schistosomiasis with indication for surgical treatment were prospectively studied. All patients underwent routine pre- and postoperative biochemical, hematologic, coagulation blood tests and intraoperative portal hemodynamic evaluation (portal pressure and portal flow) before and after esophagogastric devascularization and splenectomy using a 4-F thermodilution catheter introduced inside the portal vein. RESULTS: Portal vein thrombosis, diagnosed by routine postoperative Doppler ultrasonography was found in 22 patients (55%). It was partial in nineteen and total in three. In patients with postoperative portal thrombosis, we observed a reduction in portal flow of 971 +/- 592 mL/min (42 +/- 16%) at the end of the surgery, while this reduction was of 720 +/- 644mL/ min (33 +/- 30%) in those with postoperative pervious portal vein (p = 0.245). The decrease in portal pressure was the same in both groups: 7.2 +/- 3.0 mmHg (23 +/- 10%) and 7.6 +/- 3.8 mmHg (27 +/- 14%) with and without thrombosis respectively (p=0.759). There was also no significant difference between patients with and without portal vein thrombosis regarding pre- and postoperative hemoglobin level or platelet levels, coagulation tests, portal vein diameter and spleen's weight. CONCLUSIONS: Portal vein thrombosis was observed in 55% of the patients but this complication did not show any correlation with the decrease in portal flow or pressure or with biochemical, hematologic, coagulation blood tests, portal vein diameter or spleen's weight.     

Circadian rhythm of serum cytidine deaminase in patients with rheumatoid arthritis during rest and exercise.

Circadian rhythm of serum cytidine deaminase and C reactive protein was assessed in 11 inpatients with rheumatoid arthritis who were crossed between 24 hours of bed rest and 24 hours of normal ward activity. Blood was taken at six hourly intervals and the results analysed by fitting sine waves with an assumed period of 24 hours to the measured concentrations. Cytidine deaminase after activity, but not at rest, showed circadian variation, with a 24 hour mean level of 17.4 units (normal 3-13 units) and an amplitude of 1.1 units. The circadian variation, defined as the curve's peak to trough difference as a percentage of the 24 hour mean, was 12.3% and occurred at 1208 hours. C reactive protein showed no significant circadian rhythm, in keeping with published findings. The timing of the peak in serum cytidine deaminase concentrations after a period of morning physiotherapy, but not during the bedrest morning, suggests that exercise accounts for the circadian rhythm, probably by increasing the lymphatic clearance from inflamed joints.     

Venous dynamics in leg lymphedema

To determine whether there is anatomical and/or functional impairment to venous return in patients with lymphedema, we examined venous dynamics in 41 patients with unilateral leg lymphedema. A Volometer was used for computer analysis of leg volume, a color Duplex Doppler scanner was used to determine deep vein patency and skin thickness, and Air-plethysmography was used to assess ambulatory venous pressure, venous volume, venous filling index and the ejection fraction. In the lymphedematous leg, volume and skin thickness were uniformly increased (126.4 +/- 21.3% and 156.9 +/- 44.5%) (mean +/- S.D.), respectively. The ambulatory venous pressure was also increased (134 +/- 60.7%) as was the venous volume (124.5 +/- 37.5%), and the venous filling index (134.5 +/- 50.5%). The ejection fraction was decreased (94.9 +/- 26.1%). Greater leg volume correlated with increased venous volume and venous filling index (values = 0.327, 0.241, respectively) and decreased ejection fraction (r = -0.133). Increased subcutaneous thickness correlated with increased venous filling index and venous volume (r = 0.307, 0.126, respectively) and decreased ejection fraction (r = -0.202). These findings suggest that soft tissue edema from lymphatic stasis gradually impedes venous return which in turn aggravates the underlying lymphedema.     

The effect of upper airway obstruction and arousal on peripheral arterial tonometry in obstructive sleep apnea

We evaluated the effects of airflow limitation and arousal on digital vascular tone in 10 patients with obstructive sleep apnea (OSA) using the recently developed, noninvasive technique of peripheral arterial tonometry (PAT). Subjects were maintained at a therapeutic level of continuous positive airway pressure, and nasal pressure was acutely dropped for three to five breaths during nonrapid eye movement sleep over a range of pressures from 9.3 +/- 1.3 to 1.9 +/- 1.3 cm H2O, leading to increasing airway obstruction and decreasing levels of inspiratory airflow. In the absence of a detectable electroencephalographic (EEG) arousal, severe reductions of inspiratory airflow to below 200 ml/second caused significant decreases in PAT amplitude (1.000 +/- 0.007 to 0.869 +/- 0.007 arbitrary units; p < 0.001), whereas mild airflow limitation (> 200 ml/second) had no effect (1.000 +/- 0.009 to 1.011 +/- 0.007 arbitrary units). The presence of an EEG arousal accentuated the response to airflow obstruction, such that the PAT amplitude decreased more (p < 0.001) in the presence of arousal (1.000 +/- 0.007 to 0.767 +/- 0.010 arbitrary units) than in the absence of arousal (1.000 +/- 0.007 to 0.923 +/- 0.007 arbitrary units). We conclude that airflow obstruction in patients with OSA causes an acute digital vasoconstriction that is accentuated in the presence of an EEG arousal.     

Heparin therapy for venous thrombosis and pulmonary embolism

Intravenous heparin is the initial treatment of choice for most patients with acute pulmonary embolism or proximal deep vein thrombosis. The primary objective of initial heparin therapy in such patients is to prevent recurrent venous thromboembolism. The efficacy of intravenous heparin for this purpose has been established by randomized clinical trials in patients with pulmonary embolism, and more recently, in patients with proximal vein thrombosis. Heparin is given as an initial intravenous bolus of 5000 units, followed by a maintenance dose of 30,000-40,000 units per 24 h by continuous intravenous infusion. A recent randomized trial in patients with proximal vein thrombosis indicates that failure to achieve an adequate anticoagulant response (APTT greater than 1.5 times control) is associated with a high risk (25%) of recurrent venous thromboembolism. Intravenous heparin administered in doses that prolong the activated partial thromboplastin time (APTT) to 1.5 or more times the control value is highly effective, and associated with a low frequency (2%) of recurrent venous thromboembolism. Heparin is continued for 7-10 days, overlapped with warfarin sodium during the last 4-5 days. Multiple randomized clinical trials indicate that this approach is highly effective. An alternative approach is to commence heparin and oral anticoagulants together at the time of diagnosis, and to discontinue heparin on the fourth or fifth day. A recent randomized trial in patients with submassive venous thrombosis or pulmonary embolism suggests that 4-5 days of initial heparin therapy is effective and safe, but this approach must be evaluated by further randomized trials before it is recommended for patients with extensive proximal vein thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained improvement of pulmonary hemodynamics in patients at rest and during exercise after thrombolytic treatment of massive pulmonary embolism

This study assessed the long-term effects of thrombolytic treatment in patients with acute massive pulmonary embolism (PE). Seven patients with PE that followed deep-vein thrombosis underwent pulmonary angiography and pressure measurements before and 6 +/- 3 days (mean +/- SD) and 15 +/- 4 months after treatment with intrapulmonary infusions of urokinase (average dose 1724 U/kg X hr) and heparin (average dose 17 U/kg X hr). Treatment was guided by daily measurements of pulmonary arterial (PA) pressure and was continued until PA pressure had normalized (average of 6 days). Late after treatment patients returned for pulmonary angiographic examination, right heart catheterization at rest and during bicycle exercise, and phlebography of the deep veins of both legs. Pulmonary angiograms showed massive obstruction before therapy (Walsh index 15 +/- 2 points of a maximum of 18 points), which was improved 6 days (3 +/- 3 points) and 15 months (1 +/- 2 points) after therapy. Mean PA pressure declined from 37 +/- 9 to 13 +/- 3 mm Hg after 6 days and to 15 +/- 3 mm Hg after 15 months. No recurrence of PE was observed. In six of seven patients at rest and during bicycle exercise (up to 100 W) in the supine position mean PA pressure and total pulmonary resistance remained within normal limits. Over the short term all patients showed clinical signs of deep-vein thrombosis; 15 months later four patients had normal deep veins, but three patients had still phlebographic signs of old thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous urokinase in acute myocardial infarction

To achieve reperfusion early, an intravenous bolus of 2 million units of urokinase was administered in 50 patients with transmural acute myocardial infarction (AMI) 1.8 +/- 2.5 hours after the onset of symptoms. Coronary angiography performed 1.1 +/- 0.6 hours after urokinase therapy revealed patent coronary arteries in 30 patients (60%), with no significant difference between those with anterior and those with inferior AMI. Reocclusion occurred in only 1 of 24 patients restudied. Failure to achieve reperfusion was not related to the degree of systemic fibrinolytic activity, which was equally high in patients who did and those who did not achieve reperfusion, as evident from serially obtained fibrinogen measurements (77 +/- 52 vs 84 +/- 24 mg/dl, difference not significant). Plasmin activity, measured serially from 15 minutes to 24 hours after urokinase in 7 patients, was maximal at 15 minutes and undetectable after 3 hours. Wall motion at the infarct site measured from contrast ventriculograms was significantly better at follow-up only in patients in whom reperfusion was achieved and who received urokinase within 2 hours after the onset of symptoms as compared with patients in whom reperfusion was not achieved (-1.2 +/- 1.4 vs -2.4 +/- 0.9 standard deviations from normal, p less than 0.05). Peak serum creatine kinase level was significantly lower in patients in whom reperfusion was achieved than in those in whom it was not or those who had rethrombosis (802 +/- 763 vs 1,973 +/- 1,071 U/liter, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Do different doses of intravenous streptokinase alter the frequency of coronary reperfusion in acute myocardial infarction?

This study assessed the relative efficacy of 3 doses of intravenous streptokinase in causing hypofibrinogenemia and coronary reperfusion in patients with acute myocardial infarction. Accordingly, 56 patients (50 men and 6 women, ages 58 +/- 10 years [mean +/- standard deviation]) with evolving acute myocardial infarction and chest pain less than or equal to 5 hours in duration were assigned to receive varying doses of streptokinase. Twenty were administered 500,000 units during 145 minutes, 18 were given 750,000 units during 30 minutes and 18 received 1.5 million units in 60 minutes of streptokinase. Serum creatine kinase was measured on admission and 6, 12, 18 and 24 hours after the initiation of streptokinase. The time intervals from onset of pain to peak creatine kinase and from streptokinase administration to peak creatine kinase were used to determine the occurrence of reperfusion. The plasma fibrinogen concentration was measured 30, 60, 90 and 120 minutes after the initiation of streptokinase. For the 3 groups, the time from onset of pain to peak creatine kinase was less than 17 hours and the time from streptokinase to peak creatine kinase was 6 or 12 hours in 15 (75%), 16 (89%) and 12 patients (67%), respectively (differences not significant). The plasma fibrinogen concentration decreased to 45 +/- 34 mg/dl, 19 +/- 14 mg/dl and 29 +/- 43 mg/dl, respectively, during the 2 hours after streptokinase was begun (p less than 0.05 for the first versus the second and third values).(ABSTRACT TRUNCATED AT 250 WORDS)     

Intramuscular pressure, venous function and muscle blood flow in patients with lymphedema of the leg

Intramuscular pressure, muscle blood flow and venous emptying was studied in seven patients with unilateral lymphedema of the leg. Intramuscular pressure was measured with the wick technique. Muscle blood flow was assessed by means of the 133Xenon clearance technique. Venous emptying was studied with strain gauge technique. Intramuscular pressure in the anterior tibial compartment of the edematous leg was 30 +/- 14 mmHg at rest, rising to 49 +/- 16 mmHg during exercise (p less than 0.05). In the healthy leg the pressure rose from 16 +/- 8 mmHg at rest to 28 +/- 6 mmHg during exercise (p less than 0.05). In the deep posterior compartment similar pressure values were obtained. Muscle blood flow during exercise was significantly higher (p less than 0.05) in the healthy leg, 32.4 +/- 6.8 ml X min-1 X (100 g)-1 than in the edematous leg, 29.9 +/- 4.8 ml X min-1 X (100 g)-1. Venous emptying was significantly lower (p less than 0.05) in the diseased leg, 44.7 +/- 18.7 ml X min-1 X (100 g)-1 than in the healthy leg, 61.4 +/- 18,9 ml X min-1 X (100 g)-1. Thus, lymphatic obstruction of the leg causes edema which leads to an increased intramuscular pressure and a decreased muscle blood flow and venous emptying.