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Biomedical subjects

S Totterman

Publications and source records attributed to S Totterman.

At least 19 recordsLinked to original sources
PubMed2006

Proposal for a nomenclature for magnetic resonance imaging based measures of articular cartilage in osteoarthritis.

OBJECTIVE: Magnetic resonance imaging (MRI) of articular cartilage has evolved to be an important tool in research on cartilage (patho)physiology and osteoarthritis (OA). MRI provides a wealth of novel and quantitative information, but there exists no commonly accepted terminology for reporting these metrics. The objective of this initiative was to propose a nomenclature for definitions and names to be used in scientific communications and to give recommendations as to which minimal methodological information should be provided when reporting MRI-based measures of articular cartilage in OA. METHODS: An international group of experts with direct experience in MRI measurement of cartilage morphology or composition reviewed the existing literature. Through an iterative process that included a meeting with a larger group of scientists and clinicians (December 2nd, 2004, Chicago, IL, USA), they discussed, refined, and proposed a nomenclature for MRI-based measures of articular cartilage in OA. RESULTS: The group proposes a nomenclature that describes: (1) the anatomical location and (2) the structural feature being measured, each name consisting of a metric variable combined with a tissue label. In addition, the group recommends minimal methodological information that should be described. CONCLUSIONS: Utilization of this nomenclature should facilitate communication within the scientific community. Further, the uniform adoption of comprehensive nomenclature to describe quantitative MRI- features of articular cartilage should strengthen epidemiological, clinical, and pharmacological studies in OA.

Cartilage, Articular↗
PubMed2006

MRI and non-cartilaginous structures in knee osteoarthritis.

Magnetic resonance imaging (MRI) provides a sensitive tool for examining all the structures involved in the osteoarthritis (OA) process. While much of the MRI literature previously focussed on cartilage, there is increasing research on whole-organ evaluation and including features such as synovitis, bone marrow edema, and meniscal and ligamentous pathology. The aim of this session at the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Workshop for Consensus in Osteoarthritis Imaging was to describe the current MRI methods for identifying and quantifying non-cartilaginous structures and review their associations with both OA symptoms and structural progression. Although there is much experience in measuring synovitis (derived from the rheumatoid arthritis literature), only one study has reported an association of MRI-detected synovitis and effusions with OA pain. Bone marrow edema lesions, which may represent areas of trabecular remodelling, have been associated with pain and compartment-specific structural deterioration. MRI studies have confirmed the frequency and importance of meniscal damage in progressive cartilage loss, but not related such damage to symptoms. Osteophytes have been associated with cartilage loss and malalignment to the side of the osteophyte. Ligament damage, including anterior cruciate ligament tears, has been found more commonly than expected in painful OA knees. Improvements in quantitative and semi-quantitative assessments of non-cartilage features will greatly assist understanding of the OA process and its response to therapy.

Bone Marrow↗
PubMed2001

Three-dimensional registration and fusion of ultrasound and MRI using major vessels as fiducial markers.

This paper describes fusion of three-dimensional (3-D) ultrasound (US) and magnetic resonance imaging (MRI) data sets, without the assistance of external fiducial markers or external position sensors. Fusion of these two modalities combines real-time 3-D ultrasound scans of soft tissue with the larger anatomical framework from MRI. The complementary information available from multiple imaging modalities warrants the development of robust fusion capabilities. We describe the data acquisition, specialized algorithms, and results for 3-D fused data from phantom studies and in vivo studies of the normal human vasculature and musculoskeletal systems.

Algorithms↗
PubMed1999

A multisite phase III study of the safety and efficacy of a new manganese chloride-based gastrointestinal contrast agent for MRI of the abdomen and pelvis.

The purpose of this study was to evaluate the safety and efficacy of a manganese chloride-based oral magnetic resonance (MR) contrast agent during a Phase III multisite clinical trial. Two hundred seventeen patients were enrolled who were already scheduled for MRI of the abdomen and/or pelvis. In this group of patients, it was postulated that the use of an oral agent would better allow discrimination of pathology from bowel. Patients with known gastrointestinal pathology including peptic ulcer disease, inflammatory bowel disease, obstruction, or perforation were excluded to minimize confounding variables that could affect the safety assessment. Of these 217 patients, 18 received up to 900 mL of placebo, and 199 patients were given up to 900 mL of a manganese chloride-based oral contrast agent, LumenHance (Bracco Diagnostics, Inc.). Safety was determined by comparing pre- and post-dose physical examinations, vital signs, and laboratory examinations and by documenting adverse events. Efficacy was assessed by unblinded site investigators and two blinded reviewers who compared pre- and post-dose T1- and T2-weighted MRI scans of the abdomen and/or pelvis. In 111 (57%) of the 195 cases evaluated for efficacy by site investigators (unblinded readers), MRI after LumenHance provided additional diagnostic information. Increased information was found by two blinded readers in 52% and 51% of patients, respectively. In 44/195 cases (23%) unblinded readers felt the additional information would have changed patient diagnosis and in 50 patients (26%), it would have changed management and/or therapy. Potential changes in patient diagnosis or management/therapy were seen by the two blinded readers in 8-20% of patients. No clinically significant post-dose laboratory changes were seen. Forty-eight patients (24%) receiving LumenHance and four patients (22%) receiving placebo experienced one or more adverse events. Gastrointestinal tract side effects were most common, seen in 29 (15%) of LumenHance patients and in 3 (17%) of the placebo patients. LumenHance is a safe and efficacious oral gastrointestinal contrast agent for MRI of the abdomen and pelvis.

Abdomen↗
PubMed1998

MR image-guided portal verification for brain treatment field.

PURPOSE: To investigate a method for the generation of digitally reconstructed radiographs directly from MR images (DRR-MRI) to guide a computerized portal verification procedure. METHODS AND MATERIALS: Several major steps were developed to perform an MR image-guided portal verification procedure. Initially, a wavelet-based multiresolution adaptive thresholding method was used to segment the skin slice-by-slice in MR brain axial images. Some selected anatomical structures, such as target volume and critical organs, were then manually identified and were reassigned to relatively higher intensities. Interslice information was interpolated with a directional method to achieve comparable display resolution in three dimensions. Next, a ray-tracing method was used to generate a DRR-MRI image at the planned treatment position, and the ray tracing was simply performed on summation of voxels along the ray. The skin and its relative positions were also projected to the DRR-MRI and were used to guide the search of similar features in the portal image. A Canny edge detector was used to enhance the brain contour in both portal and simulation images. The skin in the brain portal image was then extracted using a knowledge-based searching technique. Finally, a Chamfer matching technique was used to correlate features between DRR-MRI and portal image. RESULTS: The MR image-guided portal verification method was evaluated using a brain phantom case and a clinical patient case. Both DRR-CT and DRR-MRI were generated using CT and MR phantom images with the same beam orientation and then compared. The matching result indicated that the maximum deviation of internal structures was less than 1 mm. The segmented results for brain MR slice images indicated that a wavelet-based image segmentation technique provided a reasonable estimation for the brain skin. For the clinical patient case with a given portal field, the MR image-guided verification method provided an excellent match between features in both DRR-MRI and portal image. Moreover, target volume could be accurately visualized in the DRR-MRI and mapped over to the corresponding portal image for treatment verification. The accuracy of DRR-MRI was also examined by comparing it to the corresponding simulation image. The matching results indicated that the maximum deviation of anatomical features was less than 2.5 mm. CONCLUSION: A method for MR image-guided portal verification of brain treatment field was developed. Although the radiographic appearance in the DRR-MRI is different from that in the portal image, DRR-MRI provides essential anatomical features (landmarks and target volume) as well as their relative locations to be used as references for computerized portal verification.

Brain Neoplasms↗
PubMed1998

3D visual presentation of shoulder joint motion.

The 3D visual presentation of biodynamic events of human joints is a challenging task. Although the 3D reconstruction of high contrast structures from CT data has been widely explored, then there is much less experience in reconstructing the small low contrast soft tissue structures from inhomogeneous and sometimes noisy MR data. Further, there are no algorithms for tracking the motion of moving anatomic structures through MR data. We represent a comprehensive approach to 3D musculoskeletal imagery that addresses these challenges. Specific imaging protocols, segmentation algorithms and rendering techniques are developed and applied to render complex 3D musculoskeletal systems for their 4D visual presentation. Applications of our approach include analysis of rotational motion of the shoulder, the knee flexion, and other complex musculoskeletal motions, and the development of interactive virtual human joints.

Adult↗
PubMed1997

Prevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin.

The effectiveness and safety of warfarin were compared with those of a low-molecular-weight heparin (dalteparin) for the prevention of deep-vein thrombosis after total hip arthroplasty in a prospective, randomized, multi-institutional trial. Patients who were older than eighteen years of age and were scheduled to have an elective primary or revision total hip arthroplasty were eligible; 580 patients were randomized, 550 had the operation and received prophylaxis, and 382 had evaluable venograms. Prophylaxis was provided either with warfarin beginning the night before the operation or with dalteparin beginning two hours before the operation and was continued until venography was performed. Bleeding was assessed on the basis of intraoperative blood loss, transfusion requirements, a decrease in hematocrit, and clinically identified bleeding complications. The prevalence of deep-vein thrombosis was found to be significantly lower in the patients who had received dalteparin than in those who had received warfarin (twenty-eight [15 per cent] of 192 patients compared with forty-nine [26 per cent] of 190 patients; p = 0.006). Deep-vein thrombosis occurred in the calf veins of twenty-one patients (11 per cent) who had received dalteparin and of forty-three patients (23 per cent) who had received warfarin; this difference was significant (p = 0.003). Proximal deep-vein thrombosis occurred in ten patients (5 per cent) who had received dalteparin and in sixteen patients (8 per cent) who had received warfarin; however, with the numbers available, no significant difference could be detected (p = 0.185). We also could not detect a significant difference with regard to the intraoperative and postoperative blood loss, the decrease in hematocrit, and the prevalence of major bleeding complications between the two groups; however, the patients who had received dalteparin had a significantly higher prevalence of bleeding complications involving the operative site (p = 0.03), and a significantly greater percentage required postoperative transfusions (p = 0.001). We concluded that preoperative prophylaxis with dalteparin is significantly more effective than that with warfarin in preventing deep-vein thrombosis after total hip arthroplasty. The greater effectiveness of dalteparin must be considered, however, in light of an increased need for postoperative transfusions and an increase in the prevalence of wound-related bleeding complications.

Anticoagulants↗
PubMed1996

Utility of creatinine excretion in body-composition studies of healthy men and women older than 60 y.

This study evaluated whether aging alters the usefulness of creatinine excretion as an index of lean body mass (LBM) or muscle mass in healthy men and women. Creatinine excretion was determined while 24 young (15 men and 9 women aged < 32 y) and 38 older (23 men and 15 women aged > 60 y) healthy volunteers stayed at a clinical research center for 3 d. Total LBM was determined by 40K counting in all subjects, and cross-sectional areas of upper arm and thigh muscles were determined in some subjects (10 young, 20 old) by magnetic resonance imaging. The slopes and intercepts of the regression equations relating LBM to average daily creatinine excretion were the same in the younger and older groups, and the precision with which LBM could be determined from creatinine excretion was not diminished by aging. Creatinine excretion was closely correlated with cross-sectional areas of upper arm (r = 0.85) and thigh (r = 0.88) muscles, and the slopes and intercepts of the regression equations were not significantly affected by age. The older group had a mean LBM smaller than that of the younger group, which was accounted for entirely by a smaller muscle mass. Mean resting metabolic rate (RMR), whole-body protein turnover rate, and thigh strength were lower in the older group than in the young group. Adjustment of RMR and protein turnover for creatinine excretion or LBM eliminated the age effects. Strength was lower in the older group even after adjustment for creatinine excretion or LBM. This study indicates that creatinine excretion is useful for evaluating body composition in both young and old subjects.

Adult↗
PubMed1996

Effect of age on muscle hypertrophy induced by resistance training.

BACKGROUND: Previous research has shown that resistance training induces muscle hypertrophy in older subjects, but has not clarified whether the degree of hypertrophy is affected by age. The present study was done to test the hypothesis that men and women over 60 years old have a smaller hypertrophic response to resistance training than young adults. METHODS: Cross-sectional areas (CSA) of muscle in the thigh and upper arm were determined before and after 3 months of progressive resistance training by magnetic resonance imaging (MRI) in 9 young (22-31 yr, 5 male and 4 female) and 8 old (62-72 yr, 4 male and 4 female) subjects. Strength was determined by 3-repetition-maximum (3RM) testing. The amount of weight lifted during the training program was proportional to baseline strength. RESULTS: Mean pretraining 3RM strength, per cm2 CSA, was less in the older group for all muscle groups examined (16 +/- 6% for elbow flexors, p < .02; 40 +/- 7% for knee flexors, p < .001; 19 +/- 9% for knee extensors, p < .05). Mean training-induced increases in muscle CSA were less in the older group for elbow flexors (22 +/- 4% in young, 9 +/- 4% in old, p < .05) and knee flexors (8 +/- 2% in young, 1 +/- 2% in old, p < .01), but not for knee extensors (4 +/- 1% in young, 6 +/- 2% in old). Mean training-induced increases in specific tension (ratio of 3RM strength to CSA) were similar in young and old groups for elbow flexors (21 +/- 5% in young, 19 +/- 5% in old) and knee extensors (38 +/- 6% in young, 32 +/- 14% in old), but were greater in the older group for knee flexors (28 +/- 5% in young, 64 +/- 13% in old, p < .02). CONCLUSIONS: Aging can attenuate the hypertrophic response of muscle groups to resistance training, when the training load is proportional to baseline strength. However, aging does not impair training-induced increases in specific tension.

Adult↗
PubMed1996

Comparison of two warfarin regimens in the prevention of venous thrombosis following total knee replacement.

A prospective, randomized trial was conducted to compare the effectiveness and safety of warfarin given in two regimens in prevention of venous thrombosis after total knee replacement. Adult patients scheduled for primary or revision total knee replacement were randomly assigned to receive either a "two-step" warfarin regimen beginning 10-14 days pre-operatively or, alternatively, to begin warfarin the night before surgery. Post-operatively, the dose was adjusted in both groups to achieve a target International Normalized Ratio (INR) of 2.2 and prophylaxis was continued until venography on post-operative days five through nine. Bleeding was assessed by surgical blood loss, transfusion requirements, changes in hematocrit, and clinically identified bleeding complications. The occurrence of deep vein thrombosis was nearly the same in the two treatment groups, 39% in patients randomized to the two-step regimen as compared to 38% in those beginning the night before surgery. The occurrence of proximal vein thrombosis was also similar, 5% versus 7% (p = NS). Patients in the two-step group received 1.33 +/- 1.26 transfusions compared to 0.95 +/- 1.22 in the night before group (p < 0.05) and also had a lower nadir post-operative hematocrit of 26.7 +/- 3.1 as compared to 28.5 +/- 3.2 (p < 0.0001). Major bleeding complications were associated with excessively prolonged INRs and occurred in five patients in the two-step group and two in the night before group. Patients in both groups who developed thrombosis had a significantly lower INR on post-operative days two and three compared to those without thrombosis. We conclude that a prophylactic warfarin regimen for prevention of deep vein thrombosis after total knee replacement beginning the night before surgery is more convenient and may be associated with less bleeding than a regimen beginning warfarin 10-14 days pre-operatively. Careful control of anticoagulant intensity is needed to achieve maximum effectiveness and avoidance of bleeding complications.

Adult↗
PubMed1995

Evaluation of the renal arteries in kidney donors: value of three-dimensional phase-contrast MR angiography with maximum-intensity-projection or surface rendering.

OBJECTIVE: Donors routinely undergo preoperative conventional arteriography to evaluate the renal arteries before nephrectomy. The purpose of this study was to assess the capability of three-dimensional phase-contrast MR angiograms postprocessed with maximum-intensity-projection and surface-rendering techniques to show the renal arteries of potential donors. MATERIALS AND METHODS: Postprocessed three-dimensional phase-contrast MR angiograms of 17 patients were retrospectively reviewed by two experienced radiologists for the number and length of renal arteries visualized. Conventional arteriograms were used as the reference standard. Coronal maximum-intensity-projection and surface-rendered MR angiograms were also compared with each other with regard to the delineation of renal arteries from overlapping vessels. RESULTS: MR angiograms showed all 34 single or dominant renal arteries but only eight of 10 accessory arteries seen on conventional arteriograms. One of the nonvisualized accessory arteries was located within the imaged volume, and the other one arose from the distal aorta beyond the imaged regions. Five of six arterial branches arising from the proximal 30-mm portions of the renal arteries were seen on MR angiograms. Postprocessing with either maximum-intensity projection or surface-rendering showed the same number of renal arteries, although surface rendering separated overlapping veins from the renal arteries better than the maximum-intensity-projection technique. CONCLUSION: These results suggest that three-dimensional MR angiography is a reliable method of imaging single or dominant renal arteries, but not for showing all accessory renal arteries and small arterial branches. Surface rendering may provide specific advantages over maximum-intensity-projection in delineating renal arteries from overlapping vessels.

Adult↗
PubMed1995

Magnetic resonance imaging of deep vein thrombi correlates with response to thrombolytic therapy.

Fibrinolytic therapy can result in rapid lysis of deep vein thrombi (DVT), but its use is limited by the failure of many patients to respond and by the increased risk of bleeding complications in comparison with anticoagulant therapy alone. Treatment could be improved by the ability to select patients most likely to respond. Since magnetic resonance (MR) imaging may be sensitive to thrombus age and structure, properties related to thrombolytic sensitivity, we have evaluated the ability of MR imaging to predict the response of DVT to thrombolytic therapy. Nine patients with venographically documented proximal DVT were treated with streptokinase, and MR imaging using a gradient recall echo sequence was performed before and after therapy. The proximal leg veins were divided into nine segments in each patient, and thrombus was present in 55 segments. The MR appearance of the thrombus in each segment was evaluated prior to therapy, and the amount of clot lysis was determined by comparing pre- and post-treatment MR images. MR imaging accurately identified thrombus in all cases in comparison with venography and also identified proximal extension into pelvic veins that was not identified venographically. Prior to treatment, the thrombus in eight of nine patients varied in appearance in different vein segments consistent with a course of progressive extension over time. Thrombi with low MR signal occurred more often in patients with symptoms of four days or less, and were also more common in partially occluded segments (10/12, 83%) than with total occlusion (7/43, 16%) (p < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Deep venous thrombosis following total hip arthroplasty. Effects of prolonged postoperative epidural anesthesia.

The authors studied the use of epidural anesthesia prolonged to 48 hours of epidural analgesia in 120 total hip arthroplasty patients in a case-control fashion. One half of the patients received prolonged epidural anesthesia, while the other matched half received general endotracheal anesthesia. Venograms were obtained after surgery and graded in blind fashion by a single radiologist. The overall incidence of deep venous thrombosis in the epidural versus general anesthetic groups was 23 (14 of 60 patients) versus 40% (24 of 60) (P < .05). There was an identical incidence--8.3% (5 of 60 patients)--of proximal thrombosis in the two groups, and all of the difference in the overall rates of thrombosis occurred in the calf. Fifteen percent (9 of 60 patients) of the epidural patients and 31.6% (19 of 60) of the general anesthetic patients demonstrated this finding (P < .05). Of the 10 proximal clots, 8 (80%) were found in the operative leg, while only 29 (59.2%) of the 49 calf clots were found in the operative leg. Prolonged epidural anesthesia significantly decreases the incidence of deep venous thrombosis after total hip arthroplasty, with its most apparent benefit on calf vein thrombosis secondary to its hyperkinetic effect on lower limb blood flow. The observation that it has no demonstrable effect on the prevention of proximal thrombosis and our finding that the majority of proximal clots are in the operative leg suggest that thrombi in the thigh may be the result of a different primary pathogenic mechanism that is more related to endothelial injury than to changes in viscosity or blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia, Epidural↗
PubMed1993

Quiz: case report 776. Chondromyxoid fibroma of femur.

CMF is a rare neoplasm of bone, comprising less than 1% of primary bone tumors. The neoplasm was first described in 1948 by Jaffe and Lichtenstein as a separate entity from chondrosarcomas, having slightly different plain film characteristics and a benign clinical course. As of 1985, Kreicbergs, Lonnquist, and Willems estimated that approximately 400 cases have been published. Recently, we encountered a CMF with an unusual clinical presentation. The efficacy of MRI studies is shown.

Adult↗
PubMed1993

Embolic complications of calf thrombosis following total hip arthroplasty.

The incidence of clinically significant pulmonary embolism following total hip arthroplasty is reported in patients with venographically documented deep venous thrombosis. One hundred seventy-four patients who enrolled in a prospective evaluation of deep venous thrombosis prophylaxis underwent contrast venography 7-10 days after operation. Ten patients with proximal and 12 patients with isolated deep calf thrombosis were identified on routine venogram reading and received appropriate anticoagulant therapy, including a 6-12-week course of warfarin. There were no clinically evident embolic events and no bleeding complications in this group. A secondary blinded review of venograms several weeks later identified isolated deep calf thrombi in 13 other patients, none of whom had received warfarin after discharge. Four of the 13 patients (P < .02) subsequently presented with pulmonary embolism at a mean of 33.5 days after operation. Asymptomatic deep calf venous thrombosis following total hip arthroplasty is associated with a significant risk of developing clinically evident pulmonary embolism within the first 8 weeks after operation. Once identified, these thrombi were effectively managed with outpatient warfarin anticoagulation, and both embolic and bleeding complications were avoided. This study documents the need for more prolonged routine prophylaxis against venous thrombosis than has heretofore been the rule, extending beyond the time of discharge from the hospital. Alternatively, the authors' experience supports the use of routine screening venography following total hip arthroplasty to allow detection and selective anticoagulant treatment of deep venous thrombosis in both the thigh and calf.

Hip Prosthesis↗
PubMed1992

Comparison of warfarin and external pneumatic compression in prevention of venous thrombosis after total hip replacement.

OBJECTIVE: To compare the effectiveness and safety of warfarin and external pneumatic compression (EPC) in prevention of venous thrombosis after total hip replacement. DESIGN: Prospective, randomized trial in consecutive patients, with blinded assessment of the primary end point. SETTING: University medical center and large community hospital. PATIENTS: Patients over age 18 years scheduled for elective primary total hip replacement were eligible. Of 254 patients interviewed, 232 were randomized, 220 patients had surgery and received prophylaxis, and 201 had venography. INTERVENTIONS: Patients were randomly assigned to prophylaxis with a device providing bilateral sequential EPC to both the calf and thigh or to receive warfarin in a low-intensity regimen beginning 10 to 14 days preoperatively. Prophylaxis was continued until venography. MAIN OUTCOME MEASURES: Venous thrombosis was diagnosed by venography between postoperative days 6 and 8. Bleeding was assessed by surgical blood loss, transfusion requirements, changes in hematocrit, and clinically identified bleeding complications. RESULTS: The total incidence of venous thrombosis was virtually the same in the warfarin and EPC groups (31% vs 27%), but the distribution of thrombi was different. Proximal thrombosis occurred in 12% of patients in the EPC group compared with only 3% in the warfarin group (P = .012, 95% confidence interval for difference, 2% to 18%). In contrast, calf vein thrombosis was more frequent in the warfarin group (21%) than in the EPC group (12%) (P = .021, 95% confidence interval for difference, 0% to 18%). Most proximal thrombi in EPC-treated patients were located within 15 cm of the femoral head and were not continuous with thrombi in deep calf veins. The high incidence of proximal thrombosis in the EPC group resulted in termination of the study by the safety monitoring committee. Blood loss and bleeding complications were similar in the two groups. CONCLUSION: Warfarin therapy is significantly more effective than EPC in preventing serious proximal vein thrombosis after total hip replacement. The greater effectiveness of warfarin therapy in preventing proximal vein thrombi and of EPC in preventing thrombosis in the calf suggests that there are differences in the pathogenesis of thrombosis in these two locations.

Aged↗
PubMed1992

Comparison of dosage schedules of rt-PA in the treatment of proximal deep vein thrombosis.

This study assessed the efficacy and safety of increasing durations of constant-dose intravenous recombinant tissue-type plasminogen activator (rt-PA) in the treatment of deep vein thrombosis. Patients with venogram-documented proximal lower limb (popliteal, iliofemoral) or upper limb (axillary, subclavian) thrombi were given an initial 2-hour rt-PA infusion at 4 micrograms/kg/min, followed by a maintenance infusion of 1 microgram/kg/min for an additional 4, 22, or 33 hours (mean total rt-PA dosages of 54, 127, and 185 mg). A new quantitative venogram scoring system was applied to the study, based on measurements of thrombus volume before and after completion of treatment. Whereas none of the seven patients given treatment for 6 hours and only one of four given treatment for 24 hours showed significant lysis, four of seven who received a prolonged infusion for 35 hours showed lysis of more than 40% of the original thrombus. Overall, the prolonged 35-hour infusion induced 51% lysis of original thrombus, representing a thrombus volume of 16.7 ml dissolved. Hemorrhagic complications were common in all three groups, with four of 18 patients having significant bleeding, including one massive gastrointestinal hemorrhage, two patients with a decrease in hematocrit of more than 10%, and one patient with an intracranial hemorrhage who recovered completely. Pharmacokinetics of the rt-PA showed a steady state antigen concentration of 240 ng/ml and activity of 200 IU/ml during the initial 2-hour infusion and a postinfusion half-life of 5 minutes. Plasma fibrinogen concentrations decreased to approximately 40% to 50% of initial values with all three treatment regimens, but the nadir fibrinogen concentrations did not correlate with either therapeutic efficacy or bleeding complications. One patient with systemic lupus erythematosus had an unusual allergic reaction that manifested primarily as angioedema. This study suggests that rt-PA infusion of 35 hours induces greater thrombolysis of deep vein thrombosis than does a shorter course of 6 or 24 hours, without an increase in hemorrhagic complications.

Adult↗