Biomedical subjects
W T Jackson
Publications and source records attributed to W T Jackson.
Pharmacologic actions of the second generation leukotriene B4 receptor antagonist LY29311: in vivo pulmonary studies.
We examined the in vivo actions of LY293111 sodium (2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]pro poxy]phenoxy] benzoic acid sodium salt). Guinea pigs were used to evaluate the effect of this agent on (1) acute airway obstruction produced by intravenous leukotriene B4, (2) pulmonary granulocyte infiltration and delayed onset airway obstruction resulting from a 4-h leukotriene B4 inhalation and (3) lung inflammation after aerosol challenge with the divalent cationic ionophore A23187 (6S-[6alpha(2S*,3S*),8beta(R*),9beta,11alpha]-5- (methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol-2-yl)e thyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazole carboxylic acid). Airway obstruction was quantitated using pulmonary gas trapping measurements and lung inflammation was evaluated by bronchoalveolar lavage (BAL) and histology. LY293111 sodium produced a dose-related inhibition of acute leukotriene B4-induced airway obstruction when administered i.v. (ED50=14 microg/kg) or p.o. (ED50=0.4 mg/kg). In contrast, LY293111 sodium did not inhibit the pulmonary gas trapping caused by aerosols of histamine, leukotriene D4, or the thromboxane mimetic U46619 (15 [(S)-hydroxy11a,9a-(epoxymethano)prosta-5Z,13E-dienoic acid]). Oral LY293111 sodium inhibited leukotriene B4-induced bronchoalveolar lavage granulocyte infiltration and delayed onset airway obstruction at doses as low as 0.3 mg/kg. In A23187-challenged animals, pulmonary inflammation was markedly inhibited at 1 h, but not 2 h and 4 h post-exposure. We conclude that LY293 11 sodium is a selective leukotriene B4 receptor antagonist with potent pulmonary anti-inflammatory activity.
Cognitive orientation in rehabilitation and neuropsychological outcome after traumatic brain injury.
This study evaluated the ability of the Orientation Log (O-Log) to predict cognitive outcome at rehabilitation discharge, as well as future neuropsychological outcome. The hypothesis was that patients who demonstrated better orientation upon admission would achieve superior functional cognitive outcome at discharge and on subsequent neuropsychological assessment. Sixty individuals receiving inpatient rehabilitation following a new-onset TBI participated. Orientation data was collected using the O-Log during morning bedside rounds. Outcome data was collected at 6 and 12 months post-injury. Significant correlations were found between the O-log and measures of memory, executive functioning, basic verbal skills, and estimated intellectual ability. When compared to the other predictor variables, step-wise multiple regression analyses revealed that the minimum O-Log score was the primary significant predictor of performance on six neuropsychological and functional outcome measures. Results of this study suggest that evaluating orientation with the O-Log during acute rehabilitation may reflect level of injury severity and aid in predicting cognitive outcome.
Pharmacologic actions of the second-generation leukotriene B4 receptor antagonist LY293111: in vitro studies.
The in vitro actions were investigated of LY293111, a potent and selective leukotriene B4 (LTB4) receptor antagonist, on human neutrophils, human blood fractions, guinea pig lung membranes, and guinea pig parenchymal and tracheal strips. The IC50 for inhibiting [3H]LTB4 binding to human neutrophils was 17.6 +/- 4.8 nM. LY293111 inhibited LTB4-induced human neutrophil aggregation (IC50 = 32 +/- 5 nM), luminol-dependent chemiluminescence (IC50 = 20 +/- 2 nM), chemotaxis (IC50 = 6.3 +/- 1.7 nM), and superoxide production by adherent cells (IC50 = 0.5 nM). Corresponding responses induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine were inhibited by 100-fold higher concentrations of LY293111. LTB4 binding to guinea pig tissues and subsequent activation were also inhibited. The Ki for inhibition of [3H]LTB4 binding to lung membranes was 7.1 +/- 0.8 nM; IC50 for preventing binding of [3H]LTB4 to spleen membranes was 65 nM. The compound inhibited LTB4-induced contraction of guinea pig lung parenchyma. At 10 nM, LY293111 caused a parallel rightward shift of the LTB4 concentration-response curve. At higher concentrations, plots were shifted in a nonparallel manner, and maximum responses were depressed. LY293111 did not prevent antigen-stimulated contraction of sensitized trachea strips. At micromolar concentrations, LY293111 inhibited production of LTB4 and thromboxane B2 by plasma-depleted human blood stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine and thrombin. In addition, at these higher concentrations, formation of LTB4 by A23187-activated whole blood and conversion of arachidonic acid to LTB4 by a human neutrophil cytosolic fraction were inhibited. In summary, LY293111 is a second-generation LTB4 receptor antagonist with much improved potency in a variety of functional assay systems.
Visual reproduction subtest of the Wechsler Memory Scale-Revised: analysis of construct validity.
This study assessed the construct validity of Visual Reproduction (VR) Cards A (Flags) and B (Boxes) from the original Wechsler Memory Scale (WMS) compared to Flags and Boxes from the revised edition of the WMS (WMS-R). Independent raters scored Flags and Boxes using both the original and revised scoring criteria and correlations were obtained with age, education, IQ, and four separate criterion memory measures. Results show that for Flags, there is a tendency for the revised scoring criteria to produce improved construct validity. For Boxes, however, there was a trend in the opposite direction, with the revised scoring criteria demonstrating worse construct validity. Factor analysis suggests that Flags are a more distinct measure of visual memory, whereas Boxes are more complex and significantly associated with conceptual reasoning abilities. Using the revised scoring criteria, Boxes were found to be more strongly related to IQ than Flags. This difference was not found using the original scoring criteria.
Effective serial measurement of cognitive orientation in rehabilitation: the Orientation Log.
OBJECTIVE: To introduce a brief quantitative measure of cognitive orientation (to place, time, and situation) developed for daily use at bedside with rehabilitation inpatients. The Orientation Log (O-Log) is a 10-item scale that allows for partial credit based on responsiveness to logical, multiple-choice, or phonemic cueing. It is formatted for rapid visual analysis of orientation trends that can be used to evaluate pharmacologic and cognitive-behavioral interventions. DESIGN: Descriptive study of the O-Log's reliability (interrater and internal consistency). SETTING: Inpatient rehabilitation center affiliated with a large university medical school. PATIENTS: Fifteen neurorehabilitation inpatients. RESULTS: For individual items, Spearman rho interrater reliability coefficients ranged from .851 to 1.00. The interrater reliability of the total score was .993. O-Log internal consistency (coefficient alpha) was .922. CONCLUSIONS: The O-Log is a reliable and easily administered scale that promises to be a useful tool in monitoring cognitive recovery during rehabilitation.
Radiology of the sacroiliac joint.
STUDY DESIGN: Radiology of the sacroiliac joint was investigated by obtaining different and multiple radiographs of cadaveric pelves marked with solder metal wire and radiopaque paint. OBJECTIVES: To demonstrate the orientation of the sacroiliac joint on various, radiographic views. SUMMARY OF BACKGROUND DATA: Interpretation of the sacroiliac joint projection on plain radiography is difficult. It requires an understanding and appreciation of its components and their orientation. Emphasizing the definition of the orientation of the plane of the joint on the different projection views of the sacroiliac joints can aid the orthopaedic surgeon in obtaining the proper radiographs and in the proper interpretation of the different radiographic views. METHODS: Nineteen sacroiliac joints from 10 cadaveric pelves, 5 male and 5 females were studied. Each joint was found to be composed of three portions: anterosuperior, middle, and posteroinferior portions, each lying in a different plane. Each sacroiliac joint was marked with solder wires and radiopaque paint to define the orientation of each of the three portions of the joint on radiographs. The following radiographic projection views were taken for each joint anteroposterior, lateral, inlet, craniocaudal axial, outlet, lithotomy and oblique views. For the oblique views, the angulation of the x-ray tube needed to view each portion of the joint tangentially was recorded. RESULTS: There was a wide variation in the orientation of the planes of the joint portions between the right and the left sides as well as between different pelves. Although the twisting of the plane of the whole joint produced by the successive examination of the portions could be either internal or external, it was the same bilaterally in a given specimen. The outlet and lithotomy views provided the best tangential representation of the two sacroiliac joints on one film. CONCLUSION: The sacroiliac joint is composed of three portions oriented in different planes. To study the sacroiliac joints, it seems desirable to obtain an anteroposterior view of the pelvis with the patient in a lithotomy position; then, if needed, each joint can be radiographed separately by using oblique views. It is important to not that the plane of the articular portion of the joint can be directed from anterolateral to posteromedial, and therefore, the oblique views should be obtained accordingly.
The discovery of LY293111, a novel, potent and orally active leukotriene B4 receptor antagonist of the biphenylphenol class.
Explore the source record for details and available documents.
Anatomic considerations for posterior iliac bone harvesting.
STUDY DESIGN: This study analyzed bony features of the posterior ilium and relevant vital structures using cadavers and dry ilium specimens. OBJECTIVES: To determine quantitatively the safely zone of the posterior ilium and relevant vital structures with regard to bone graft harvesting. SUMMARY OF BACKGROUND DATA: The most frequently used site for bone graft harvesting is the posterior ilium. However, complications related to posterior iliac bone harvesting, such as donor site pain, neurovascular injury, instability of the sacroiliac joint, and herniation of abdominal contents, are still major concerns. Very little research with regard to the quantitative study of the posterior ilium has been reported. METHODS: Six cadavers (four male, two female) were used for the first part of this study. The posterior superior iliac spine was determined as a reference landmark. The distances from the posterior superior iliac spine to the superior cluneal nerves, the gluteal line, and the superior gluteal vessels were measured. The second part of the study involved 30 adult, dry iliac bony specimens. The posterior iliac region (extra-articular portion) was divided into three zones, and the corresponding dimensions of these zones were measured. RESULTS: The average distances from the posterior superior iliac spine to the superior cluneal nerves, gluteal line, and superior gluteal vessels were 68.8, 26.6, and 62.4 mm, respectively. The average width, height, and maximum thickness for Zone 1 were 34, 27.8, and 17.1 mm, respectively; the measurements for Zone 2 were 16.5, 31.8, and 14.2 mm, respectively. The average height for Zone 3 was 20.4 mm, and the average maximum thickness was 16.8mm. CONCLUSION: The ideal area of the posterior ilium for bone graft harvesting was found in Zone 1. Zones 2 or 3 may be considered it a greater quantity of cancellous bone graft is required; however, the risk of injury to the sacroiliac joint and superior gluteal vessels in these zones is increased.
Anatomic consideration of C2 pedicle screw placement.
STUDY DESIGN: This anatomic study tested placement of C2 pedicle screws using cadaver specimens. OBJECTIVES: To further assess the safety of transpedicular screw placement in the axis by comparing two surgical techniques. SUMMARY OF BACKGROUND DATA: Transpedicular screw fixation of traumatic spondylolisthesis of the axis has been described in the literature. Recently, anatomic studies and clinical applications of transpedicular screw fixation for traumatic lesions of middle and lower cervical spine have been described. No previous study assessing the safety of C2 pedicle screw placement is available. METHODS: Sixteen embalmed cadaveric specimens were used for this study. In the first eight specimens (Method A), the point of entry for screw placement was chosen to be about 5 mm inferior to the superior border of C2 lamina and 7 mm lateral to the lateral border of the spinal canal. The screw direction was chosen to be about 30 degrees medial to the sagittal plane and 20 degrees cephalad to the transverse plane. A 3.5-mm cortical screw of appropriate length, determined with depth gauge, was placed bilaterally into the C2 pedicle. In the next eight specimens (Method B), the direction of the drill bit was guided directly by the medial and superior aspect of the individual C2 pedicle. Gross dissection was done to view violation of dura, nerve roots, vertebral artery, and penetration of medial, lateral, superior, and inferior cortex of the C2 pedicle. Radiographs and computed tomography scans were obtained to evaluate screw placement in the C2 pedicle. RESULTS: In Method A, four screws had lateral violations into the vertebral artery. In Method B, only two cases of minimal penetration of pedicle cortex were found. No medial, superior, or inferior violation of the pedicle cortex was found in the present study. CONCLUSIONS: The present anatomic study suggests that transpedicular screw fixation may be performed safely in the C2 pedicle by using the second technique. Using the first technique is not safe.
Development of novel anti-inflammatory agents: a pharmacologic perspective on leukotrienes and their receptors.
Explore the source record for details and available documents.
Anatomic and X-ray film studies of the distal articular surface of the radius.
Knowledge of the surgical and topographic anatomy of the distal articular surface of the radius is valuable during diagnostic and operative procedures involving the distal radius. The aim of this study is to assist the surgeon in determining the location, displacement, and angulation of acute or healed distal radius articular fractures. Measurements were taken of the distal articular surface of 50 dry radii. Also, the margins and surfaces of the distal articular surface of 12 adult cadaver radii were marked by solder and radiopaque dye, respectively. X-ray films were then taken to define the margins and bony landmarks. The lunate facet surface area (53%) was found to be slightly larger than the scaphoid facet surface area (47%). Both the palmar tilt and the radial inclination were demonstrated on the marked x-ray films. Using the 30 degrees cephalad angled anteroposterior projection of the distal radius can help assess the dorsomedial fragment of the lunate fossa in a die-punch fracture.
Anatomic considerations for the anterior exposure of the proximal portion of the radius.
The rate of posterior interosseous nerve injury is still of major concern during surgical exposure of the proximal portion of the radius. The objective of this study was to find the best way to protect the important neurovascular structures during anterior exposure of the proximal radius and to define the safest anatomic orientation for plate and screw placement during open reduction and internal fixation of the proximal radius. In 30 cadaveric upper limbs, the proximal portion of the radius was exposed through a modified anterior Henry approach. The important anatomic structures were localized and demonstrated on radiographs. Plates and screws were applied anterolaterally (in five specimens) and laterally (in another five specimens), and the locations of the safe and danger zones were noted. Lateral placement of the plate is preferred over the more commonly used anterolateral plating, because it carries less risk of injuring the posterior interosseous nerve during screw application and it does not impinge on the biceps tendon and block pronation.
Femoral neck fracture following intertrochanteric fracture.
Four patients with femoral neck fracture following healed intertrochanteric fracture were evaluated retrospectively. This situation is a rare occurrence with a current literature review documenting only 15 cases. Patient charts and radiographs were retrospectively reviewed to evaluate the period from initial injury to definitive treatment for the femoral neck fracture. Emphasis was placed on associated risk factors and operative techniques. In case 1, the femoral neck fracture appeared to be clearly a traumatic fracture as it occurred 11 years after the intertrochanteric fracture. In cases 2, 3, and 4, multiple factors were believed to play a role in the generation of the femoral neck fractures, which occurred within 6 months of the original fracture. The etiology of such fractures remains speculative. All four patients were elderly, women with substantial medical comorbidities. Osteoporosis may be the most important single contributing factor to these fractures. Because management of this patient subgroup is notably more complex, surgeons need to be aware of the difficulties and prepared to deal with them.
Aerosolized LTB4 produces delayed onset increases in pulmonary gas trapping.
Airway obstruction, as measured by increases in postmortem pulmonary gas trapping, and lung inflammatory changes were examined in guinea pigs exposed for up to 4 h to aerosols of leukotriene B4 (LTB4) or its non-chemotactic isomer, 6-trans-12-epi-LTB4. Airway obstruction and cytological responses in isomer-exposed animals were similar to those of unexposed control animals. LTB4-exposed animals had minimal inflammatory changes at 0.5 h but became dyspneic by 2 h and had increased airway obstruction, bronchoalveolar lavage neutrophils and eosinophils, and pulmonary tissue granulocyte scores. The LTB4-induced effects at 4 h were similar to those 2 h, except for further increase in BAL neutrophils and eosinophils. LTB4-induced airway obstructive and inflammatory changes were prevented by pretreatment with the LTB4 receptor antagonist SC-41930, but were unaffected by indomethacin. Thus, prolonged LTB4 inhalation can produce delayed onset airway obstruction that is stereospecific, cyclooxygenase-independent, and temporally associated with the influx of granulocytes into lung airways.
Neurochemical mechanisms in brain injury and treatment: a review.
This article reviews cellular energy transformation processes and neurochemical events that take place at the time of brain injury and shortly thereafter emphasizing hypoxia-ischemia, cerebrovascular accident, and traumatic brain injury. New interpretations of established concepts, such as diffuse axonal injury, are discussed; specific events, such as free radical production, excess production of excitatory amino acids, and disruption of calcium homeostasis, are reviewed. Neurochemically-based interventions are also presented: calcium channel blockers, excitatory amino acid antagonists, free radical scavengers, and hypothermia treatment. Concluding remarks focus on the role of clinical neuropsychologists in validation of treatment interventions.
Extensile medial approach to the femur.
A proposed extensile medial approach to the medial surface of the shaft of the femur was studied on 30 cadaver thighs. The incision is made along a line extending from the mid inguinal point to a point one-third the distance from the adductor tubercle to the medial side of the patella. After mobilizing the sartorius muscle posteromedially, the medial femur is exposed by a three-step technique. Step I involves bluntly defining the internervous plane distally between the vastus medialis muscle and the adductor magnus tendon until limited proximally by the distal end of the vastoadductor membrane at an average of 9 cm from the adductor tubercle. In step II blunt dissection between the vastus medialis and the adductor longus muscles is carried from proximal to distal until limited by the proximal end of the vastoadductor membrane. Now the well-defined vastoadductor membrane area ("danger zone") measuring 6 cm in length on average is safely dealt with (step III) and the medial femur is exposed. Distal extension can be made to expose the knee joint. The approach can be extended proximally to the lesser trochanter between the vastus medialis and both the adductor brevis and pectineus muscles. Anatomic measurements in relation to the adductor tubercle and cross-sections of the thigh were made to better describe anatomic constants and variables in this rather unfamiliar medial thigh area.
Anatomical considerations of irreducible medial subtalar dislocation.
Irreducible medial subtalar dislocation has been associated with the talar head "buttonholing" through the extensor digitorum brevis (EDB) muscle, entrapment of the talar head in the extensor retinaculum, talonavicular impaction, interpositioning of the EDB muscle between the talus and navicular, and buttonholing of the talar head through the talonavicular ligament and joint capsule. Cadaver analysis of the medial subtalar dislocation in this study supported entrapment of the talar head in the extensor retinaculum and talonavicular impaction as well as impingement of the deep peroneal nerve and associated dorsalis pedis arterial branches between the talus and navicular as causes of irreducible subtalar dislocation. In this study, the talar head was not noted to buttonhole through or entrap the EDB muscle. This is the first report of the deep peroneal nerve implicated as a possible cause of irreducible medial subtalar dislocation.