Transsection of the peroneal nerve complicating knee arthroscopy: case report and cadaver study.
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Arthroscopy↗
Biomedical subjects
W F Bennett
Publications and source records attributed to W F Bennett.
Pathology of the adrenal gland: imaging features.
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Adrenal Gland Diseases↗
The hyperdense liver and spleen: a CT manifestation of barium embolization through a duodenocaval fistula.
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Aged↗
Comparative study of continuous extrapleural intercostal nerve block and lumbar epidural morphine in post-thoracotomy pain.
OBJECTIVES: To compare the efficacy of continuous extrapleural intercostal nerve block with bupivacaine 0.5% in 1:200,000 epinephrine and continuous lumbar epidural block with morphine in controlling post-thoracotomy pain and to measure serum bupivacaine concentrations during extrapleural infusion. DESIGN: A prospective, randomized, controlled trial. SETTING: St. Joseph's Hospital, Hamilton, Ont., a tertiary care teaching centre. PATIENTS: Sixty-one patients booked for elective thoracotomy were randomized by scaled envelope to two groups. INTERVENTIONS: Group A received a continuous extrapleural intercostal nerve block with bupivacaine 0.5% in 1:200,000 epinephrine as a bolus of 0.3 mL/kg followed by an infusion of 0.1 mL/kg every hour for 72 hours. Group B received a continuous lumbar epidural block with morphine as a bolus of 70 g/kg followed by an infusion of 7 g/kg every hour for 72 hours. MAIN OUTCOME MEASURES: Pain was assessed by a linear visual analogue scale (VAS) pain score. The cumulative amount of "rescue" intravenous morphine used, and serum bupivacaine concentrations were measured as secondary outcomes. RESULTS: Pain control was the same in both groups as assessed by linear VAS score (p = 0.33). The cumulative dose of intravenous morphine for supplemental analgesia was statistically significant between the groups: group A patients used more morphine than group B (p < 0.05). Accumulation of serum bupivacaine was present with no clinical toxicity. CONCLUSIONS: There is no significant difference in the degree of post-thoracotomy pain control measured by the VAS score when analgesia is provided by continuous extrapleural intercostal nerve block with bupivacaine 0.5% in 1:200,000 epinephrine or lumbar epidural block with morphine. Larger amounts of rescue analgesia were used by patients in the continuous extrapleural group with bupivacaine than those in the continuous lumbar epidural block with morphine. Serum bupivacaine concentrations rise without clinical toxicity.
Analgesia, Epidural↗
Locating the unpaired cysteine of tissue-type plasminogen activator.
Variants of tissue-type plasminogen activator (t-PA) were constructed with selected cysteines replaced by alanine to evaluate the role of an unpaired cysteine, which has been presumed to be in the growth factor module. C75A, C83A, C84A and CC83-84AA variants of t-PA were expressed transiently in human embryonic kidney cells. The biochemical properties of these variants provided experimental evidence to identify the unpaired cysteine in t-PA. Assays of amidolytic activity, plasminogen activation (in the presence or absence of fibrinogen or fibrin), plasma clot lysis, fibrin binding, clearance in mice, and interaction with a panel of monoclonal antibodies were performed as the basis for comparing these variants with wild-type t-PA. In all assays, C83A t-PA was biochemically equivalent to wild-type t-PA. C75A t-PA, C84A t-PA and CC83-84AA t-PA variants exhibited reduced activities in a variety of functional assays. These variants displayed two-to threefold lower activity in fibrinogen or fibrin stimulated plasminogen activation, and fivefold reduced plasma clot lysis activity compared with that of wild-type t-PA. The affinity of C75A t-PA and C84A t-PA for fibrin was decreased more than two orders of magnitude compared with C83A t-PA or wild-type t-PA. Plasma clearance of C75A t-PA and C84A t-PA was reduced 2-fold in mice. The C75A, C84A and CC83-84AA variants displayed significantly decreased reactivity with anti-tPA monoclonal antibodies specific for finger/growth factor domain epitopes. These data are consistent with a disulfide linkage of Cys75 with Cys84 and that Cys83 exists as an unpaired sulfhydryl. The significance of the unpaired cysteine is as yet undetermined since C83A t-PA and wild-type t-PA are functionally equivalent.
Amino Acid Sequence↗
Limiting systemic plasminogenolysis reduces the bleeding potential for tissue-type plasminogen activators but not for streptokinase.
Clinical experience suggests that thrombolytic-induced bleeding is associated with systemic activation of the thrombolytic system. Using fibrin specific variants of tissue-type plasminogen activator (t-PA) and making use of the apparent fibrin specificity of streptokinase (SK) in the rabbit we tested the hypothesis that minimizing systemic plasmin production and fibrinogenolysis will decrease hemorrhages in models of peripheral bleeding and embolic stroke. t-PA consumed 51% of the available fibrinogen; caused cerebral bleeds and increased peripheral bleeding time. Fibrin-specific variants of t-PA depleted less than 20% of the fibrinogen and did not cause peripheral or cerebral bleeding. However, an equipotent dose of SK converted only 12% of the available fibrinogen but increased bleeding time and caused hemorrhagic conversion in 75% of embolic stroke model animals treated. The data suggest that bleeding associated with tissue-type plasminogen activators is linked to systemic plasmin generation and subsequent fibrinogenolysis. This hypothesis does not explain the mechanism(s) of SK-induced bleeding.
Animals↗
New variant of human tissue plasminogen activator (TPA) with enhanced efficacy and lower incidence of bleeding compared with recombinant human TPA.
BACKGROUND: The thrombolytic properties of a new variant of tissue plasminogen activator (TPA) (T103N, N117Q, KHRR 296-299 AAAA, or TNK-TPA) with longer plasma half-life, greater fibrin specificity, and increased resistance to inhibition by plasminogen activator inhibitor (PAI-1) were investigated in a rabbit thrombosed carotid artery model. METHODS AND RESULTS: After 60 minutes of arterial occlusion, TPA (1.5, 3.0, 6.0, or 9.0 mg/kg as a front-loaded IV infusion for 90 minutes; n = 22) or TNK-TPA (0.38, 0.75, or 1.5 mg/kg as IV bolus; n = 16) was administered. Blood flow through the artery was monitored for an additional 120 minutes. Bleeding was assessed by weighing the amount of blood absorbed in a gauze pad placed in a subcutaneous muscular incision. Recanalization rates and duration of recanalization were dose dependent. The doses that produced > 80% recanalization rates with the longest duration of recanalization were 9.0 mg/kg for TPA and 1.5 mg/kg for TNK-TPA. At these doses, time to reperfusion (mean +/- SEM) was significantly faster (11 +/- 2 versus 23 +/- 7 minutes) and duration of recanalization longer (77 +/- 9 versus 51 +/- 18 minutes) for TNK-TPA compared with TPA (P < .025). Weights of the residual thrombi of the TPA group were greater than those of the TNK-TPA group (P = .004). Concentrations of fibrinogen, plasminogen, and alpha 2-antiplasmin at 120 minutes were significantly higher for TNK-TPA-treated animals compared with TPA-treated animals (P < .001). ANOVA of the blood loss data determined that there were significant differences between thrombolytic agents but not between doses. After correction for saline controls, total blood loss for pooled doses of TPA and TNK-TPA was 82 +/- 6 mg and 40 +/- 4 mg, respectively (P < .01). CONCLUSIONS: From these data, we conclude that TNK-TPA, given as a bolus, produces faster and more complete recanalization of occluded arteries in a rabbit experimental model compared with TPA, without increasing systemic plasmin generation or peripheral bleeding. In addition, we observed that TNK-TPA, unlike TPA, did not potentiate collagen-induced aggregation of platelets obtained from human plasma. This lack of effect on platelet aggregation by TNK-TPA potentially could be associated with a decreased risk of reocclusion after successful thrombolysis.
Animals↗
Intravenous aspirin causes a paradoxical attenuation of cerebrovascular thrombolysis.
BACKGROUND AND PURPOSE: Aspirin treatment is recognized as an advantageous adjunct to thrombolytic agents in myocardial infarct patients. In this study we examined the effects of aspirin on the rate of clot lysis and on the frequency and extent of hemorrhagic transformations in rabbit models of embolic stroke. METHODS: Rabbit models of ex vivo platelet aggregation and cutaneous template bleeding times were used to show the anticoagulant effects of aspirin in our experimental paradigm. We monitored tissue-type plasminogen activator (TPA)-induced clot lysis in two rabbit models of embolic stroke by (1) scintigraphically following the dissolution of a 99mTc-tagged clot or (2) using roentgenography to follow the disappearance of an Sn-tagged clot. RESULTS: In animals pretreated (18 hours) with a single administration of aspirin (1, 5, or 20 mg/kg IV) or 1 mg/kg per day for 3 days, the aggregation response of platelets to collagen (3.3 micrograms/mL) or arachidonic acid (0.5 mmol/L) was attenuated. High-dose aspirin also increased ear template bleeding time from 1.6 to 2.6 minutes. When aspirin (20 mg/kg) was administered 18 hours before embolism and subsequent lysis with TPA (0.3 mg/kg bolus; 3 mg/kg per hour IV), the pretreatment significantly antagonized the rate and extent of TPA-induced clot lysis by up to 70%. This was confirmed in a second embolic stroke model. The suppression of TPA-induced lysis was reversed by administration of the prostacyclin analogue iloprost (10 micrograms/kg per hour) directly into the cerebral circulation. CONCLUSIONS: We conclude that aspirin reduces the effects of TPA in embolic stroke models. This effect may be the result of a loss of endothelial prostacyclin production since the effect is reversed by iloprost.
Animals↗
Arthroscopic lateral portals revisited. A cadaveric study of the safe zones.
Lateral knee portal placement is defined by and divided into five anatomic zones (A through E) beginning just anterolateral to the patellar ligament and proceeding posteriorly at 1-cm intervals. The arthroscopic anatomy and the open dissected lateral knee anatomy are correlated in this study with a fresh frozen cadaver. Zone A includes the anterolateral capsulosynovial layer and zone B includes the anterolateral capsulosynovial layer, anterior portion of the iliotibial tract, and the patellotibial ligament. The lateral capsulosynovial layer and the middle-to-posterior portion of the iliotibial tract comprise zone C. Zone D includes the lateral collateral ligament, the popliteal tendon, and the anterior border of the long head of the biceps femoris tendon. The mid-portion of the long head of the biceps femoris tendon and the peroneal nerve make up zone E. Structures penetrated are defined as safe in zones A, B, and C, and unsafe in zone E. Structures that are potentially penetrable are defined as relatively at risk in zone D. When placing a portal for arthroscopic visualization of the posterolateral compartment of the knee, the placement should be between zone D and the anterior portion of zone E at 90 degrees of knee flexion. This potential space is between the lateral collateral ligament and the anterior portion of the biceps femoris tendon; it enlarges with increasing knee flexion and allows for easier portal placement.
Arthroscopy↗
Scintigraphic visualization of pulmonary thrombi with 123I-YPACK-TNK-tPA.
BACKGROUND: We have previously demonstrated that radiolabeled tissue-type plasminogen activation (tPA) in which the plasminogen-activating catalytic site has been inactivated binds avidly to thrombi and can be used for scintigraphic detection of pulmonary thrombi in vivo. The present study was performed to overcome identified limitations of the initially developed approach and to determine whether a tracer made with a molecular variant of tPA, TNK-tPA, would provide superior images of pulmonary thrombi and hence facilitate differential diagnosis of pulmonary embolism from acute myocardial infarction. It was thought that TNK-tPA may be superior in view of its longer biological half-life and less avid uptake by macrophages that would otherwise contribute to high background because of non-clot-selective uptake of the tracer. METHODS: 123I-tyrosylprolylarginyl chloromethyl ketone (123I-YPACK-TNK-tPA) was infused into the systemic circulation of dogs with either pulmonary or right ventricular thrombi induced with thrombogenic tips of modified guide wires. Planar and single-photon emission computed tomography (SPECT) scintigraphic data were obtained, and blood and tissue samples were acquired for analysis of the distribution of the radiotracer over time. RESULTS: Tracer cleared from blood with an alpha phase half-life of 10 +/- 1 min, paralleling the clearance of unlabeled TNK-tPA. Only minimal release of labeled fragments from liver into blood occurred during the entire time course of the imaging studies. Pulmonary thrombi were visualized with SPECT within 30-120 min in all dogs. Images were superior to those obtained after infusion of labeled wild-type tPA, primarily because of diminished background radioactivity and consequently increased scintigraphic contrast. In one dog which had a right ventricular thrombus, the thrombus was readily detectable in both planar and SPECT images. CONCLUSIONS: Radiolabeled TNK-tPA in which plasminogen-activating activity has been inhibited biochemically is an excellent radiopharmaceutical for prompt scintigraphic detection of pulmonary and ventricular thrombi in vivo, and an attractive candidate for rapid, sensitive and non-invasive diagnosis of pulmonary thromboembolic disease in patients.
Amino Acid Chloromethyl Ketones↗
Mediastinoscopy as a routine outpatient procedure.
We reviewed our experience performing mediastinoscopy as an outpatient procedure. From January 1, 1987, to December 31, 1992, 1,015 of 1,062 cervical mediastinoscopies were performed on an outpatient basis. There were no operative deaths. Complications developed in 14 patients, 10 of whom required hospitalization. Two additional patients were hospitalized for social reasons. Supraventricular arrhythmia was the most frequent complication requiring admission to the hospital. This article documents the ability to perform mediastinoscopy safely as an outpatient procedure and discusses why this is our preferred approach in managing patients with lung cancer.
Ambulatory Care↗
Operative treatment of the rheumatoid shoulder.
Rheumatoid arthritis can affect almost any joint. Shoulder involvement typically occurs late in the disease process and usually after other joints have manifested arthritic change. Any of the four shoulder articulations can be involved: scapulothoracic, acromioclavicular, sternoclavicular, and glenohumeral. In addition to bony involvement, many of the soft tissues of the shoulder joint can be affected. Early operative treatment includes synovectomy with or without bursectomy, which is indicated prior to radiographic evidence of arthritis. Early synovectomy provides for a slowing of the progression of the disease process. Patients who have incapacitating pain with loss of range of motion can benefit from total shoulder replacement. Most patients experience pain relief and some restoration of motion. The restoration of normal range of motion is dependent on anatomic reconstruction of the glenohumeral joint. Factors that can affect the range of motion include rotator cuff tears and the general health status and motivation of the patient. Although there is a 30% to 80% incidence of radiographic lucencies with nonconstrained prostheses, their presence does not indicate the need for revision surgery. Occasionally, there is medialization of the glenohumeral joint with central bony losses of the glenoid. The surgeon should try to bone graft the defect and lateralize the components. If there is massive medialization of the glenoid that is not reconstructable, then a hemiarthroplasty is the procedure of choice.
Arthritis, Rheumatoid↗
A long-half-life and fibrin-specific form of tissue plasminogen activator in rabbit models of embolic stroke and peripheral bleeding.
BACKGROUND AND PURPOSE: We compared the activity of a new long-half-life, fibrin-specific tissue-type plasminogen activator (TPA) variant with that of wild-type TPA in rabbit models of embolic stroke and peripheral bleeding. METHODS: In the embolic stroke model. TPA-induced clot lysis is followed by continuous monitoring of a radiolabeled clot lodged in the middle cerebral artery. Twenty-four hours after embolization and treatment with either thrombolytic agent or excipient, the brains are removed, fixed, and evaluated for cerebral hemorrhage. In a parallel template bleeding time experiment, the effects of equipotent doses of the two TPA molecules were measured. RESULTS: Infusion of wild-type TPA or bolus administration of the TPA variant resulted in dose-dependent clot lysis. The TPA variant was found to be an order of magnitude more potent than wild-type TPA on a milligram-per-kilogram basis. Unlike wild-type TPA, the variant caused less systemic activation of plasminogen (P < .05) and fewer hemorrhagic transformations in this model (P < .05). The TPA variant did not extend template bleeding times. CONCLUSIONS: These findings show that by combining increased fibrin specificity with decreased plasma clearance, it is possible to produce a thrombolytic agent that is more convenient and more potent than wild-tpe TPA. At the same time the significant reduction in hemorrhagic conversions may be attributable to the conservation of systemic plasminogen seen with this molecule.
Animals↗
Tibial plateau fractures: a study of associated soft tissue injuries.
Tibial plateau fractures can occur concomitant with injuries to the collateral and cruciate ligaments, menisci, and surrounding nerves and arteries. The purpose of this article is to record the frequency of these soft tissue injuries with tibial plateau fractures. Patients with plateau fractures were entered into a prospective protocol consisting of radiographic evaluation, Schatzker classification, pre- and postfixation stress testing, and diagnostic arthroscopy. Thirty tibial plateau fractures were evaluated in this study. There was a 56% (17 of 30) frequency of associated soft tissue injuries in this series of tibial plateau fractures. The medial collateral ligaments were injured in 20% (six of 30), the lateral collateral ligaments in 3% (one in 30), the menisci in 20% (six in 30), the peroneal nerve in 3% (one in 30), and the anterior cruciate ligaments in 10% (three in 30). Schatzker type IV and type II fracture patterns were associated with the highest frequency of soft tissue injuries. Medical collateral ligament injuries were most commonly associated with Schatzker type II fracture patterns. Menisci were most commonly injured with Schatzker type IV fracture patterns. Based on the findings, routine arthroscopy should be indicated in nondisplaced Schatzker type I fractures. Pre- and postfixation stress testing should be performed to diagnose collateral and cruciate ligament injuries.
Adult↗
Lateral ankle sprains. Part I: Anatomy, biomechanics, diagnosis, and natural history.
An understanding of the anatomy and biomechanics of the lateral ankle ligaments is essential to make a proper diagnosis in patients with ankle sprains. Specific radiographic stress tests can aid in differentiating single-versus double-ligament injuries and in determining their severity. Inadequately treated ankle sprains can result in chronic pain, instability, and early osteoarthritis. Thus, the proper diagnosis and initial treatment are important. This paper reviews the essential features of the anatomy, biomechanics, diagnosis, and natural history of lateral ankle sprains.
Ankle Injuries↗
Lateral ankle sprains. Part II: Acute and chronic treatment.
This paper reviews the treatment alternatives for acute and chronic lateral ankle ligament sprains. Inadequately treated ankle sprains can result in chronic lateral ankle instability, disabling pain, and the early onset of osteoarthritis. There are a multitude of reconstructive techniques used for chronic lateral ankle instability. Morbidity associated with present techniques includes loss of proprioception, stiffness following cast immobilization, loss of subtalar motion, loss of internal rotation of the talus during ankle plantar flexion, and recurrent instability. In addition, this paper reviews the reconstructive techniques used for chronic lateral ankle instability, addresses the shortcomings of current reconstructive techniques, and proposes alternatives that may help decrease associated morbidity.
Acute Disease↗
Identification of carbohydrate structures in glycoprotein peptide maps by the use of LC/MS with selected ion extraction with special reference to tissue plasminogen activator and a glycosylation variant produced by site directed mutagenesis.
Electrospray ionization mass spectrometry utilizing a single quadrupole on line with reversed-phase HPLC (LC/MS) enables the characterization of glycoproteins in a relatively short period of time. In this approach the protein is digested with a suitable protease and the peptides are separated by reversed-phase HPLC and detected by electrospray ionization mass spectrometry. The glycopeptides are initially observed as a cluster of negatively sloping ions in a contour plot of data from the LC/MS run (m/z vs retention time) or as a characteristics series of masses at different elution times. The search for a particular glycopeptide is based on previously known carbohydrate structures and on consensus glycosylation sites. Further structural information is obtainable with glycosidase digestion and LC/MS analysis. The mass shifts following glycosidase digestion allow further confirmation of the structure. This approach identifies the site of attachment of two hybrid glycoforms to the T11 tryptic peptide in a reversed-phase tryptic map of recombinant tissue plasminogen activator (rt-PA). Use of selected ion extraction of the LC/MS data files allows one to graphically describe the elution order of closely related glycopeptides. The potential of LC/MS for the characterization of small amounts of unknown glycoproteins is shown by the study of an rt-PA mutant. A new potential site for glycosylation is created by site directed mutagenesis of wild type rt-PA with replacement of a threonine residue with asparagine at residue 103. An examination of a tryptic map shows that the mutant contains two new complex carbohydrate chains. The introduction of the new asparagine proximal to asparagine 117 changes this native high-mannose site in rt-PA to a complex-type glycosylation. This method allows rapid identification of carbohydrate containing peptides and yields useful structural information on microgram amounts of material.
Amino Acid Sequence↗
A variant of t-PA (T103N, KHRR 296-299 AAAA) that, by bolus, has increased potency and decreased systemic activation of plasminogen.
In the accompanying paper, we reported that the properties of decreased plasma clearance rate, increased fibrin specificity, and resistance to inactivation by PAI-1 could be effectively combined in the t-PA variant T103N, KHRR 296-299 AAAA. In the current study we evaluated the in vivo efficacy of this variant as well as variants containing the individual mutations T103N and KHRR 296-299 AAAA. Plasma clearance and in vivo lysis of whole blood and platelet-rich clots were determined in a rabbit arterio-venous shunt model. The T103N containing variants were administered as an intravenous (i.v.) bolus. KHRR 296-299 AAAA and t-PA were infused i.v. over 90 min. The clearance rate of the KHRR 296-299 AAAA variant was similar to t-PA. However, the clearance of the T103N and T103N, KHRR 296-299 AAAA variants were 8 and 6-fold reduced, respectively. Potency of the variants relative to t-PA on whole blood clots ranged from 0.9 (T103N, KHRR 296-299 AAAA) to 1.7 (T103N). Relative potency on platelet-rich clots ranged from 2.4 (T103N) to 4.2 (T103N, KHRR 296-299 AAAA). Fibrinogen concentrations in rabbits 120 min after dosing with a 2.5 mg/kg bolus were: 24, 16, 82, and 77% of initial for t-PA; T103N; KHRR 296-299 AAAA; and T103N, KHRR 296-299 AAAA treatment groups, respectively. These results suggest that the T103N, KHRR 296-299 AAAA variant of t-PA, given as a bolus, could result in greater efficacy, particularly on refractory platelet-rich clots, without inducing the severe systemic lytic state produced by a bolus of a less fibrin specific variant.
Animals↗