To determine if a slight modification of the 1987 Eaton-Glickel staging and interpreting 4 standa... more To determine if a slight modification of the 1987 Eaton-Glickel staging and interpreting 4 standardized radiographs for trapeziometacarpal (TMC) osteoarthritis (OA) improved analysis, to determine if a quantifiable index measurement from a single Robert (pronated anteroposterior) view enhanced reproducibility, and to examine whether improved radiographic staging correlated to clinically relevant disease and thus support validity. We analyzed 4 thumb radiographs (posteroanterior, lateral, Robert, and stress views) in 60 consecutive subjects representing an adult population spectrum of asymptomatic to advanced disease. Two experienced hand surgeons (A.L.L. and A.P.C.W.), 1 chief resident (A.J.B.), and 1 medical student (J.M.M.) performed the analysis on each subject's radiographs. We analyzed all 4 radiographs for Eaton and modified Eaton staging and then later analyzed only the Robert view for the thumb osteoarthritis (ThOA) index measurement. The radiographs were randomized and reread a week later for each classification at separate times. Surgically excised trapeziums from 20/60 subjects were inspected for first metacarpal surface disease and correlated to the 3 classifications. All 3 staging classifications demonstrated high reproducibility, with the intraclass correlation coefficient averaging 0.73 for the Eaton, 0.83 for the modified Eaton, and 0.95 for the ThOA index. Articular wear and metacarpal surface eburnation correlated highest to the ThOA index, with advanced disease 1.55 or greater correlating to Eaton III/IV and modified Eaton stage 3/4 in a linear relationship. The ThOA index based on a Robert view provided a measurable alternative to Eaton staging and correlated to severity of surgically relevant thumb TMC OA. A simple reproducible radiographic measurement may enhance TMC OA classification and provide a reliable means to predict clinical disease. Diagnostic II.
Objective Contradictory reported arthritic patterns of the metacarpal surface of the trapezium in... more Objective Contradictory reported arthritic patterns of the metacarpal surface of the trapezium include preferential volar wear, radial wear, and dorsal-ulnar sparing. We investigated whether a predominant wear pattern exists in surgical trapeziectomy for advanced thumb carpometacarpal (CMC) arthritis. Methods We examined 36 intact trapezia from 34 thumb CMC arthroplasty patients over an 18-month period. The first metacarpal articular surface revealed three consistent morphology patterns: (1) saddle, (2) dish, and (3) cirque. The saddle represented cartilage loss with preservation of the normal trapezial morphology. The dish shape represented concave curvature, with loss of the normal saddle configuration. The cirque shape represented preferential volar concave wear, disrupting the convex volardorsal arc. Two surgeons classified the randomized specimens twice, blinded to patient identity and each other's categorization. Radiographic Eaton staging was correlated retrospectively for 35 of 36 of the trapezial specimens. Eight specimens were further quantified with micro-computed tomography (micro-CT). Results Thirty-six trapezia were classified as follows: 17 (47%) saddle, 12 (33%) dish, and 7 (19%) cirque. Intra-rater reliability was 0.97 and 0.95; inter-rater reliability in the second round was 0.95. The 36 trapezia represented 27 female (75%) and 9 male (25%) patients; 18 (50%) represented the dominant hand. Age at surgery averaged 64 (33-76). Complete cartilage loss of the entire metacarpal surface was seen in 15 (42%) of all specimens. Osteophyte presence was typically minimal in the saddle group; the dish group had characteristic extensive rimming osteophytes in a 91% female population (11/12), and the cirque group had volar osteophytes. Radiographic severity ranged from Eaton stage II to IV; less severe radiographic staging (Eaton II) predominated in the saddle configuration; advanced Eaton III-IV disease predominated in both cirque and dish shapes. Micro-CT verified the three discrete shapes with volardorsal and radioulnar orientation measurements. Conclusion The metacarpal surface of the trapezium demonstrates three distinct patterns of wear in arthritic surgical specimens. Sex, dominance, age distribution, and Eaton stage varied across the different shapes. Level of Evidence Level 3 Study Type Observational.
Medical media resources exist in a variety of analog and digital formats. Collections are general... more Medical media resources exist in a variety of analog and digital formats. Collections are generally organized and stored by their owners, each of whom utilizes their own method of cataloging and retrieval. As faculty retire, move on, or pass away, institutions risk losing the expertise that enhances the value media. The Stanford MediaServer has previously been deployed to catalog, organize,
The ability to reach, grasp, transport, and release objects is essential for activities of daily ... more The ability to reach, grasp, transport, and release objects is essential for activities of daily living. The objective of this study was to develop a quantitative method to assess upper limb motor deficits in children with cerebral palsy (CP) using three-dimensional motion analysis. We report kinematic data from 25 typically developing (TD) children (11 males, 14 females; ages 5–18 years)
The purpose of the study was to evaluate the feasibility of Norian SRS bone cement injected percu... more The purpose of the study was to evaluate the feasibility of Norian SRS bone cement injected percutaneously into a distal radius following reduction in both preventing loss of reduction as well as safety. The study was a prospective clinical study with an established protocol. The study was conducted at the Massachusetts General Hospital following approval of the institutions Investigational Review Board. All patients were required to read and approve an informed consent document. While twenty patients' radiographs fulfilled the requirement of a dorsally displaced extraarticular fracture to have occurred within 72 hours of presentation, only five consented to participate fully and one voluntarily withdrew after a six-month follow-up. All fractures were reduced under regional or general anesthesia, and the Norian SRS was introduced via a catheter system into the metaphyseal defect of the fracture. A short arm cast was applied and remained in place for six weeks. Radiographic parameters of fracture reduction were measured prospectively by an independent radiologist throughout the 12 months of the study. Clinical parameters of hand and wrist function were measured prospectively by an independent occupational therapist. At 12-month follow-up, radial length was a mean 9.9 mm with an average loss of < 1 mm; radial angle maintained at a mean 25.4 degrees; volar angle was within normal range (0-21 degrees) in 4; and 1 patient had a dorsal angle of 7 degrees. Wrist motion improved 50 percent between 6 weeks and 3 months and improved further by 12 months when grip strength reached a mean of 88 percent of the contralateral side. Dorsal and volar extrusion of injected Norian SRS in 4 patients resorbed over time. There were no clinically significant adverse effects or complications. Norian SRS proved to be clinically safe and effective as a cancellous bone cement to maintain fracture reduction of unstable extraarticular distal radius fractures.
The Journal of Bone and Joint Surgery (American), 2008
Functional loss is a common complication of the fractured distal part of the radius. The purpose ... more Functional loss is a common complication of the fractured distal part of the radius. The purpose of the present study was to determine if the moment arms of the first dorsal extensor compartment are altered by distal radial fracture malunion. We hypothesized that the moment arms of the abductor pollicis longus and extensor pollicis brevis are significantly affected by dorsal angulation, radial inclination, and radial shortening, the most common deformities accompanying distal radial malunion. Moment arms of the extensor pollicis brevis and abductor pollicis longus were estimated in twelve cadaver wrists with use of the tendon-displacement method, which involves calculating the moment arm as the derivative of tendon displacement with respect to joint angle. Tendon displacement was quantified in different wrist postures before and after a closing-wedge osteotomy simulating a complex malunion of an extra-articular radial fracture. The simulated distal radial malunion resulted in a decrease in the wrist flexion moment arm for both the extensor pollicis brevis (p = 0.0003) and the abductor pollicis longus (p < 0.0001). The wrist flexion moment arms for the extensor pollicis brevis and abductor pollicis longus decreased by a mean (and standard deviation) of 114% +/- 75% and 77% +/- 50%, respectively, after the osteotomy. The wrist radial deviation moment arms for the extensor pollicis brevis and abductor pollicis longus increased by 16% +/- 26% (p = 0.071) and 28% +/- 44% (p = 0.043), respectively, after the osteotomy. Radiographs of the wrist that were made before and after the osteotomy indicated that radial tilt changed from 11.1 degrees of volar angulation to 14.8 degrees of dorsal angulation, radial inclination decreased from 21.8 degrees to 7.7 degrees, and radial height decreased from 11.6 to 4.4 mm. Distal radial malunion alters the mechanical advantage of the muscles in the first dorsal extensor compartment.
The Journal of Bone and Joint Surgery (American), 2006
The thrombin peptide, TP508, also known as Chrysalin (OrthoLogic, Tempe, Arizona), is a twenty-th... more The thrombin peptide, TP508, also known as Chrysalin (OrthoLogic, Tempe, Arizona), is a twenty-three-amino-acid peptide that represents a portion of the receptor-binding domain of the native human thrombin molecule that has been identified as the binding site for a specific class of receptors on fibroblasts and other cells. Preclinical studies with this peptide have shown that it can accelerate tissue repair in both soft and hard tissues by mechanisms that appear to involve up-regulation of genes that initiate a cascade of healing events. These events include recruitment and activation of inflammatory cells, directed migration of cells (chemotaxis), cell proliferation, elaboration of extra-cellular matrix, and accelerated revascularization of the healing tissues. Early preclinical dermal wound-healing studies showed that TP508 accelerated healing of both incisional wounds and full-thickness excisional wounds in normal and ischemic skin. In all of these studies, the accelerated healing was associated with increased neovascularization across the incision or in the granulating wound bed. Studies in a rat fracture model have also shown that TP508 accelerates the rate of fracture repair. Gene array analysis of fracture callus from control and TP508-treated fractures indicated that TP508 treatment was associated with an up-regulation of early response elements, inflammatory mediators, and genes related to angiogenesis. Similar to what had been seen in dermal wounds, histology from rat fracture callus twenty-one days after treatment indicated that fractures treated with TP508 had significantly more large functional blood vessels than did fractures in the control animals. In vitro studies support these in vivo data and indicate that TP508 may have a direct angiogenic effect by promoting the rate of new vessel growth. The results from phase-1 and phase-2 human clinical studies have shown a positive stimulatory effect of TP508 in the healing of diabetic ulcers and in the repair of fractures to the distal aspect of the radius. Collectively, these studies suggest that TP508 accelerates tissue repair by initiating a cascade of events that lead to an increased rate of tissue revascularization and regeneration.
The Journal of Bone and Joint Surgery (American), 2012
Stability and mobility represent the paradoxical demands of the human thumb carpometacarpal joint... more Stability and mobility represent the paradoxical demands of the human thumb carpometacarpal joint, yet the structural origin of each functional demand is poorly defined. As many as sixteen and as few as four ligaments have been described as primary stabilizers, but controversy exists as to which ligaments are most important. We hypothesized that a comparative macroscopic and microscopic analysis of the ligaments of the thumb carpometacarpal joint would further define their role in joint stability. Thirty cadaveric hands (ten fresh-frozen and twenty embalmed) from nineteen cadavers (eight female and eleven male; average age at the time of death, seventy-six years) were dissected, and the supporting ligaments of the thumb carpometacarpal joint were identified. Ligament width, length, and thickness were recorded for morphometric analysis and were compared with use of the Student t test. The dorsal and volar ligaments were excised from the fresh-frozen specimens and were stained with use of a triple-staining immunofluorescent technique and underwent semiquantitative analysis of sensory innervation; half of these specimens were additionally analyzed for histomorphometric data. Mixed-effects linear regression was used to estimate differences between ligaments. Seven principal ligaments of the thumb carpometacarpal joint were identified: three dorsal deltoid-shaped ligaments (dorsal radial, dorsal central, posterior oblique), two volar ligaments (anterior oblique and ulnar collateral), and two ulnar ligaments (dorsal trapeziometacarpal and intermetacarpal). The dorsal ligaments were significantly thicker (p < 0.001) than the volar ligaments, with a significantly greater cellularity and greater sensory innervation compared with the anterior oblique ligament (p < 0.001). The anterior oblique ligament was consistently a thin structure with a histologic appearance of capsular tissue with low cellularity. The dorsal deltoid ligament complex is uniformly stout and robust; this ligament complex is the thickest morphometrically, has the highest cellularity histologically, and shows the greatest degree of sensory nerve endings. The hypocellular anterior oblique ligament is thin, is variable in its location, and is more structurally consistent with a capsular structure than a proper ligament.
To determine if a slight modification of the 1987 Eaton-Glickel staging and interpreting 4 standa... more To determine if a slight modification of the 1987 Eaton-Glickel staging and interpreting 4 standardized radiographs for trapeziometacarpal (TMC) osteoarthritis (OA) improved analysis, to determine if a quantifiable index measurement from a single Robert (pronated anteroposterior) view enhanced reproducibility, and to examine whether improved radiographic staging correlated to clinically relevant disease and thus support validity. We analyzed 4 thumb radiographs (posteroanterior, lateral, Robert, and stress views) in 60 consecutive subjects representing an adult population spectrum of asymptomatic to advanced disease. Two experienced hand surgeons (A.L.L. and A.P.C.W.), 1 chief resident (A.J.B.), and 1 medical student (J.M.M.) performed the analysis on each subject's radiographs. We analyzed all 4 radiographs for Eaton and modified Eaton staging and then later analyzed only the Robert view for the thumb osteoarthritis (ThOA) index measurement. The radiographs were randomized and reread a week later for each classification at separate times. Surgically excised trapeziums from 20/60 subjects were inspected for first metacarpal surface disease and correlated to the 3 classifications. All 3 staging classifications demonstrated high reproducibility, with the intraclass correlation coefficient averaging 0.73 for the Eaton, 0.83 for the modified Eaton, and 0.95 for the ThOA index. Articular wear and metacarpal surface eburnation correlated highest to the ThOA index, with advanced disease 1.55 or greater correlating to Eaton III/IV and modified Eaton stage 3/4 in a linear relationship. The ThOA index based on a Robert view provided a measurable alternative to Eaton staging and correlated to severity of surgically relevant thumb TMC OA. A simple reproducible radiographic measurement may enhance TMC OA classification and provide a reliable means to predict clinical disease. Diagnostic II.
Objective Contradictory reported arthritic patterns of the metacarpal surface of the trapezium in... more Objective Contradictory reported arthritic patterns of the metacarpal surface of the trapezium include preferential volar wear, radial wear, and dorsal-ulnar sparing. We investigated whether a predominant wear pattern exists in surgical trapeziectomy for advanced thumb carpometacarpal (CMC) arthritis. Methods We examined 36 intact trapezia from 34 thumb CMC arthroplasty patients over an 18-month period. The first metacarpal articular surface revealed three consistent morphology patterns: (1) saddle, (2) dish, and (3) cirque. The saddle represented cartilage loss with preservation of the normal trapezial morphology. The dish shape represented concave curvature, with loss of the normal saddle configuration. The cirque shape represented preferential volar concave wear, disrupting the convex volardorsal arc. Two surgeons classified the randomized specimens twice, blinded to patient identity and each other's categorization. Radiographic Eaton staging was correlated retrospectively for 35 of 36 of the trapezial specimens. Eight specimens were further quantified with micro-computed tomography (micro-CT). Results Thirty-six trapezia were classified as follows: 17 (47%) saddle, 12 (33%) dish, and 7 (19%) cirque. Intra-rater reliability was 0.97 and 0.95; inter-rater reliability in the second round was 0.95. The 36 trapezia represented 27 female (75%) and 9 male (25%) patients; 18 (50%) represented the dominant hand. Age at surgery averaged 64 (33-76). Complete cartilage loss of the entire metacarpal surface was seen in 15 (42%) of all specimens. Osteophyte presence was typically minimal in the saddle group; the dish group had characteristic extensive rimming osteophytes in a 91% female population (11/12), and the cirque group had volar osteophytes. Radiographic severity ranged from Eaton stage II to IV; less severe radiographic staging (Eaton II) predominated in the saddle configuration; advanced Eaton III-IV disease predominated in both cirque and dish shapes. Micro-CT verified the three discrete shapes with volardorsal and radioulnar orientation measurements. Conclusion The metacarpal surface of the trapezium demonstrates three distinct patterns of wear in arthritic surgical specimens. Sex, dominance, age distribution, and Eaton stage varied across the different shapes. Level of Evidence Level 3 Study Type Observational.
Medical media resources exist in a variety of analog and digital formats. Collections are general... more Medical media resources exist in a variety of analog and digital formats. Collections are generally organized and stored by their owners, each of whom utilizes their own method of cataloging and retrieval. As faculty retire, move on, or pass away, institutions risk losing the expertise that enhances the value media. The Stanford MediaServer has previously been deployed to catalog, organize,
The ability to reach, grasp, transport, and release objects is essential for activities of daily ... more The ability to reach, grasp, transport, and release objects is essential for activities of daily living. The objective of this study was to develop a quantitative method to assess upper limb motor deficits in children with cerebral palsy (CP) using three-dimensional motion analysis. We report kinematic data from 25 typically developing (TD) children (11 males, 14 females; ages 5–18 years)
The purpose of the study was to evaluate the feasibility of Norian SRS bone cement injected percu... more The purpose of the study was to evaluate the feasibility of Norian SRS bone cement injected percutaneously into a distal radius following reduction in both preventing loss of reduction as well as safety. The study was a prospective clinical study with an established protocol. The study was conducted at the Massachusetts General Hospital following approval of the institutions Investigational Review Board. All patients were required to read and approve an informed consent document. While twenty patients' radiographs fulfilled the requirement of a dorsally displaced extraarticular fracture to have occurred within 72 hours of presentation, only five consented to participate fully and one voluntarily withdrew after a six-month follow-up. All fractures were reduced under regional or general anesthesia, and the Norian SRS was introduced via a catheter system into the metaphyseal defect of the fracture. A short arm cast was applied and remained in place for six weeks. Radiographic parameters of fracture reduction were measured prospectively by an independent radiologist throughout the 12 months of the study. Clinical parameters of hand and wrist function were measured prospectively by an independent occupational therapist. At 12-month follow-up, radial length was a mean 9.9 mm with an average loss of < 1 mm; radial angle maintained at a mean 25.4 degrees; volar angle was within normal range (0-21 degrees) in 4; and 1 patient had a dorsal angle of 7 degrees. Wrist motion improved 50 percent between 6 weeks and 3 months and improved further by 12 months when grip strength reached a mean of 88 percent of the contralateral side. Dorsal and volar extrusion of injected Norian SRS in 4 patients resorbed over time. There were no clinically significant adverse effects or complications. Norian SRS proved to be clinically safe and effective as a cancellous bone cement to maintain fracture reduction of unstable extraarticular distal radius fractures.
The Journal of Bone and Joint Surgery (American), 2008
Functional loss is a common complication of the fractured distal part of the radius. The purpose ... more Functional loss is a common complication of the fractured distal part of the radius. The purpose of the present study was to determine if the moment arms of the first dorsal extensor compartment are altered by distal radial fracture malunion. We hypothesized that the moment arms of the abductor pollicis longus and extensor pollicis brevis are significantly affected by dorsal angulation, radial inclination, and radial shortening, the most common deformities accompanying distal radial malunion. Moment arms of the extensor pollicis brevis and abductor pollicis longus were estimated in twelve cadaver wrists with use of the tendon-displacement method, which involves calculating the moment arm as the derivative of tendon displacement with respect to joint angle. Tendon displacement was quantified in different wrist postures before and after a closing-wedge osteotomy simulating a complex malunion of an extra-articular radial fracture. The simulated distal radial malunion resulted in a decrease in the wrist flexion moment arm for both the extensor pollicis brevis (p = 0.0003) and the abductor pollicis longus (p < 0.0001). The wrist flexion moment arms for the extensor pollicis brevis and abductor pollicis longus decreased by a mean (and standard deviation) of 114% +/- 75% and 77% +/- 50%, respectively, after the osteotomy. The wrist radial deviation moment arms for the extensor pollicis brevis and abductor pollicis longus increased by 16% +/- 26% (p = 0.071) and 28% +/- 44% (p = 0.043), respectively, after the osteotomy. Radiographs of the wrist that were made before and after the osteotomy indicated that radial tilt changed from 11.1 degrees of volar angulation to 14.8 degrees of dorsal angulation, radial inclination decreased from 21.8 degrees to 7.7 degrees, and radial height decreased from 11.6 to 4.4 mm. Distal radial malunion alters the mechanical advantage of the muscles in the first dorsal extensor compartment.
The Journal of Bone and Joint Surgery (American), 2006
The thrombin peptide, TP508, also known as Chrysalin (OrthoLogic, Tempe, Arizona), is a twenty-th... more The thrombin peptide, TP508, also known as Chrysalin (OrthoLogic, Tempe, Arizona), is a twenty-three-amino-acid peptide that represents a portion of the receptor-binding domain of the native human thrombin molecule that has been identified as the binding site for a specific class of receptors on fibroblasts and other cells. Preclinical studies with this peptide have shown that it can accelerate tissue repair in both soft and hard tissues by mechanisms that appear to involve up-regulation of genes that initiate a cascade of healing events. These events include recruitment and activation of inflammatory cells, directed migration of cells (chemotaxis), cell proliferation, elaboration of extra-cellular matrix, and accelerated revascularization of the healing tissues. Early preclinical dermal wound-healing studies showed that TP508 accelerated healing of both incisional wounds and full-thickness excisional wounds in normal and ischemic skin. In all of these studies, the accelerated healing was associated with increased neovascularization across the incision or in the granulating wound bed. Studies in a rat fracture model have also shown that TP508 accelerates the rate of fracture repair. Gene array analysis of fracture callus from control and TP508-treated fractures indicated that TP508 treatment was associated with an up-regulation of early response elements, inflammatory mediators, and genes related to angiogenesis. Similar to what had been seen in dermal wounds, histology from rat fracture callus twenty-one days after treatment indicated that fractures treated with TP508 had significantly more large functional blood vessels than did fractures in the control animals. In vitro studies support these in vivo data and indicate that TP508 may have a direct angiogenic effect by promoting the rate of new vessel growth. The results from phase-1 and phase-2 human clinical studies have shown a positive stimulatory effect of TP508 in the healing of diabetic ulcers and in the repair of fractures to the distal aspect of the radius. Collectively, these studies suggest that TP508 accelerates tissue repair by initiating a cascade of events that lead to an increased rate of tissue revascularization and regeneration.
The Journal of Bone and Joint Surgery (American), 2012
Stability and mobility represent the paradoxical demands of the human thumb carpometacarpal joint... more Stability and mobility represent the paradoxical demands of the human thumb carpometacarpal joint, yet the structural origin of each functional demand is poorly defined. As many as sixteen and as few as four ligaments have been described as primary stabilizers, but controversy exists as to which ligaments are most important. We hypothesized that a comparative macroscopic and microscopic analysis of the ligaments of the thumb carpometacarpal joint would further define their role in joint stability. Thirty cadaveric hands (ten fresh-frozen and twenty embalmed) from nineteen cadavers (eight female and eleven male; average age at the time of death, seventy-six years) were dissected, and the supporting ligaments of the thumb carpometacarpal joint were identified. Ligament width, length, and thickness were recorded for morphometric analysis and were compared with use of the Student t test. The dorsal and volar ligaments were excised from the fresh-frozen specimens and were stained with use of a triple-staining immunofluorescent technique and underwent semiquantitative analysis of sensory innervation; half of these specimens were additionally analyzed for histomorphometric data. Mixed-effects linear regression was used to estimate differences between ligaments. Seven principal ligaments of the thumb carpometacarpal joint were identified: three dorsal deltoid-shaped ligaments (dorsal radial, dorsal central, posterior oblique), two volar ligaments (anterior oblique and ulnar collateral), and two ulnar ligaments (dorsal trapeziometacarpal and intermetacarpal). The dorsal ligaments were significantly thicker (p < 0.001) than the volar ligaments, with a significantly greater cellularity and greater sensory innervation compared with the anterior oblique ligament (p < 0.001). The anterior oblique ligament was consistently a thin structure with a histologic appearance of capsular tissue with low cellularity. The dorsal deltoid ligament complex is uniformly stout and robust; this ligament complex is the thickest morphometrically, has the highest cellularity histologically, and shows the greatest degree of sensory nerve endings. The hypocellular anterior oblique ligament is thin, is variable in its location, and is more structurally consistent with a capsular structure than a proper ligament.
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Papers by Amy Ladd