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Biomedical subjects

P R Manske

Publications and source records attributed to P R Manske.

At least 19 recordsLinked to original sources

Quantitative variation in vascular endothelial growth factor mRNA expression during early flexor tendon healing: an investigation in a canine model.

Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis, with direct mitogenic activity on cells of endothelial origin. We quantified the temporal accumulation of VEGF mRNA at the repair site of an in vivo canine intrasynovial flexor tendon repair and rehabilitation model by means of quantitative Northern blot analysis, in order to detail a molecular signal involved in the intrinsic angiogenic process that accompanies early flexor tendon healing. Significant accumulation of VEGF mRNA occurred at the flexor tendon repair site at 7 days post-operatively, with peak levels seen at post-operative days 7 and 10. Levels returned to baseline by day 14. Local VEGF mRNA accumulation at the repair site temporally precedes and is spatially distinct from the vascular ingrowth itself, which has been shown to occur maximally at day 17. These data suggest that cells within the flexor tendon repair site are involved in molecular processes other than the synthesis of extracellular matrix, such as modulation of angiogenesis.

Animals↗

A comparison of two techniques for digital distraction lengthening in skeletally immature patients.

Since 1987, 16 skeletally immature patients aged 2 to 16 years (mean, 7.9 years) underwent 27 digital lengthening procedures of terminal bones, 20 metacarpals and 7 phalanges, using the distraction callotasis technique. Seven digits were lengthened with 2 fixator half-pins on either side of the osteotomy site (dual half-pin group). Twenty digits, which were too small to accommodate 4 half-pins, were lengthened over a longitudinal intramedullary guidewire with 1 fixator half-pin on either side of the osteotomy site (single half-pin/K-wire group). No bone grafts were needed. The mean preoperative bone length in the dual half-pin group was 30 mm (range, 23-40 mm) and that of the single half-pin/K-wire group was 18 mm (10-30 mm). The mean total length gained was 14 mm (9-23 mm) in the dual half-pin group and 12 mm (6-19 mm) in the single half-pin/K-wire group. The mean percent lengthened was 49% (22% to 96%) in the dual half-pin group and 70% (27% to 136%) in the single half-pin/K-wire group. Eighteen complications occurred: 15 in the 20 cases using the central guidewire (75%) and 3 in the 7 cases without the central guidewire (43%). Only 7 complications required repeat surgery. We conclude that the use of the single half-pin/K-wire technique allows successful and substantial lengthening for bones shorter than 23 mm, making correction surgery possible for younger children. This technique, however, has a greater risk for complications.

Adolescent↗

Involvement of ERK in BMP-2 induced osteoblastic differentiation of mesenchymal progenitor cell line C3H10T1/2.

The signaling mechanisms responsible for bone morphogenetic protein (BMP) induced osteoblast differentiation remains poorly understood. Previous research demonstrated that Smad proteins are the substrates and the mediators of BMP bound serine/threonine receptor kinase. In the present study, we examined the possible involvement of extracellular signal-regulated kinase (Erk) in the BMP induced osteoblast differentiation of mesenchymal progenitor cell C3H10T1/2. Our results indicate that BMP-2 inducement increased MAP kinase activity in mesenchymal progenitor cell line C3H10T1/2. Contrary to previous reports, this increased MAP kinase activity showed a latent but sustained pattern. Elevation of Erk1 and Erk2 protein levels was observed simultaneously. RT-PCR results demonstrated that the elevation of Erk protein level in BMP-2 induced cells was from the upregulation of mRNA expression. Furthermore, upregulated Erk proteins present enhanced phosphorylation. By using a dominant-negative Erk2 cell line, we demonstrated that nonfunctional Erk2 partially eliminated BMP-2 induced cell proliferation and ALP activity in the C3H10T1/2 cell. These results indicate that Erk is involved in BMP-2 induced osteoblast differentiation. The results also demonstrate that a latent and sustained signaling pattern exists in BMP induced signaling cascade.

Animals↗

An in vivo study of locking and grasping techniques using a passive mobilization protocol in experimental animals.

An in vivo experimental study was performed on the flexor profundus tendons of adult canines to determine tensile strength differences between locking and grasping technique repairs and to document the tensile strength using a passive mobilization protocol through the first 21 days following surgery. Forty experimental third and fourth flexor tendons of the right forepaws were lacerated and repaired with either of the 2 techniques. The experimental tendons were harvested at days 3, 7, 14, and 21 and were biomechanically tested. The third and fourth profundus tendons of the left forepaws were used as control (day 0) tendons; they were lacerated and repaired with the locking or grasping techniques at the time of harvest and also were biomechanically tested. The locking technique statistically improved tensile strength values at days 0, 3, and 21. The tensile strength decrease was minimal when using a passive mobilization protocol after surgery.

Analysis of Variance↗

A century of orthopaedic surgery at Washington University. 1899 to 1999.

The 100-year history of orthopaedic surgery at Washington University from 1899 to 1999 is presented. The history focuses on the chairmen, many of whom attained prominence in national orthopaedic organizations, other faculty members, the residency training program, and the affiliated hospitals. Orthopaedic surgery initially was organized as a department, became a division of the Department of Surgery in 1918, and recently again achieved departmental status.

Education, Medical, Graduate↗

Effect of suture size on locking and grasping flexor tendon repair techniques.

An experimental study was performed using human cadaver flexor tendons to investigate the effect of locking and grasping loop techniques on the tensile properties of repaired flexor tendons, which closely resemble the clinical model. Statistically significant improvement was observed only with the locking loop technique for ultimate and gap strength values using 2-0 core suture and ultimate strength values using 3-0 core suture. There was no statistically significant increase in tensile strength values using 4-0 core suture material. A heavier core suture used with the locking loop technique provided greater ultimate and gap strength of a repaired tendon than when used with the grasping loop technique.

Humans↗

Effect of the cross-sectional area of locking loops in flexor tendon repair.

An experimental study was performed using human cadaver flexor tendons to determine whether the size of the cross-sectional area encompassed by the locking loop suture configuration affected the biomechanical properties of tendon repair. Increasing the cross-sectional area of the locking loops from 10% to 50% resulted in a proportionate increase in the ultimate tensile strength of the repair and a small increased propensity for gapping. Overlapping the 2 locking loops without increasing the total cross-sectional area increased the propensity for gapping without increasing the ultimate strength.

Cadaver↗

The spectrum of radial longitudinal deficiency: a modified classification.

The records of 119 patients with 196 extremities with radial longitudinal deficiency seen between 1923 and 1996 were reviewed. We propose a global classification system that includes the spectrum of pathology affecting the radial side of the extremity, including deficiency of the radius, carpal abnormalities, and hypoplastic thumbs. Radial deficiency could be classified for 181 extremities of 104 patients using this classification system. Type N has a normal length radius and a normal carpus with thumb hypoplasia, type O has a normal length radius and radial side carpal abnormalities, type 1 has more than 2 mm shortening of the radius, type 2 has a hypoplastic radius, type 3 has a partial radius with absence of the distal physis, and type 4 has complete absence of the radius. All patients had thumb hypoplasia. Eighty-two percent of extremities with thumb hypoplasia but no deficiency of the radius that were available for carpal bone classification had carpal anomalies, including absence, hypoplasia, and coalitions. All the extremities with type 1 radial deficiency had carpal anomalies. Carpal abnormalities could not be determined for types 2, 3, and 4 deficiency because most had a prior centralization. Proximal radioulnar synostosis or congenital dislocation of the radial head was seen in 44% of extremities with type 1 radial deficiency. This classification includes carpal anomalies and thereby links isolated thumb hypoplasia and deficiency of the radius into one system.

Carpal Bones↗

Effect of bone morphogenetic protein-12 gene transfer on mesenchymal progenitor cells.

Recombinant adenovirus mediated human bone morphogenetic protein-12 gene transfer induced tendon and cartilage-like tissue formation in vivo. The recombinant adenovirus with the human bone morphogenetic protein-12 gene was constructed, and mature human bone morphogenetic protein-12 expression mediated by adenovirus gene transfer was detected by specific antibody. Unlike bone morphogenetic protein-2 gene transfer, bone morphogenetic protein-12 gene transferred mesenchymal progenitor cell line C3H 10T1/2 showed no change of alkaline phosphatase activity, which is the mark of cell differentiation into osteoblastic phenotype. Injection of bone morphogenetic protein-12 gene transferred C3H 10T1/2 cells into nude mice thigh muscles induced tendon and cartilage-like tissue formation. The results indicate bone morphogenetic protein-12 has different effects on mesenchymal progenitor cell differentiation, and it may influence the cell differentiation into a nonosteoblast lineage.

Adenoviridae↗

In vivo gene transfer and overexpression of focal adhesion kinase (pp125 FAK) mediated by recombinant adenovirus-induced tendon adhesion formation and epitenon cell change.

Adhesion formation is a frequent complication of tendon injury repair: however, little is known about its mechanisms. The intracellular focal adhesion kinase (FAK)-related signaling pathway may be one of the mechanisms involved in the induction of tendon adhesions. The replication deficient adenovirus containing the FAK gene (pp125 FAK) was constructed and named Adv-Fak. By in vitro transductions with the recombinant virus, overexpression of the FAK protein was documented in transduced cultured primary tendon cells. By in vivo direct injection of Adv-FAK into the space between the tendon and tendon sheath of White Leghorn chickens, FAK gene transfer with overexpression of the FAK protein was detected by immunohistological staining. The morphology of these stained cells changed from the normal flat shape to cuboid. The group with overexpressed adenovirus-mediated FAK had significant adhesion formation, as seen by increased work of flexion (118.197 +/- 29.616), compared with the group with overexpressed adenovirus-mediated beta-galactosidase (67.507 +/- 36.066) (p < 0.0393) and the group with adenovirus-mediated FAK antisense gene transfer (60.357 +/- 48.562) (p < 0.0211). Histological examination of the samples from tendons with Adv-FAK showed fibers between the tendon and tendon sheath; there were no fibers in the cavities of samples of injured tendons infected with Adv-beta gal. Moreover, at the application site of the former tendons, a thick fiber layer without epitenon cells was built up on the outer surface, whereas a thin fiber layer with clear epitenon cells was observed in the tendons to which Adv-beta gal was applied. Our results show that overexpression of FAK can induce tendon adhesion formation in vivo. This indicates that FAK and the FAK-related signaling pathway may be involved in the process of tendon adhesion formation. Understanding the details of this process may help to prevent tendon adhesion and improve healing.

Adenoviridae↗

Biomechanical and histologic characteristics of canine flexor tendon repair using early postoperative mobilization.

The purpose of this experimental study was to evaluate the mechanical and histologic healing of flexor tendon repairs using an early active motion protocol. Three different flexor tendon repair techniques in zone II were used. Forty-seven lacerated canine flexor profundus tendons from 25 dogs were repaired and evaluated at 5, 10, and 21 days after surgery. Eight of 9 Kessler repairs ruptured at days 5 and 10. None of the 19 Savage repairs or the 19 dorsal tendon splint repairs ruptured; 3 of 19 dorsal tendon splint repairs failed owing to adhesions. Smooth tendon gliding was obtained in all specimens in which repair was successful. The gap strength values for both the Savage and dorsal tendon splint repairs improved significantly for day-21 specimens compared to day-5 or day-10 specimens. The ultimate tensile strength showed no reduction during the 3-week period of tendon healing for both repairs. Histologically, there was evidence of progressive healing without surrounding adhesions. The improved suture techniques have the potential to withstand the stress produced by active digital motion protocols.

Animals↗

Effect of immobilization, immediate mobilization, and delayed mobilization on the resistance to digital flexion using a tendon injury model.

This study employed a tendon injury model in chickens to determine the effect of immobilization, immediate mobilization, and delayed mobilization on the energy required to fully flex the digit following surgical trauma to the tendon, as determined by measurement of the work of flexion (WOF). The immobilized group showed no increased WOF at 3 days compared to the zero time control values, followed by significant increased WOF at 1 week (36%), 2 weeks (41%), and 3 weeks (63%). The immediate mobilization tendons showed an initial 36% rise in the work of flexion at 3 days, which increased to 40% at 1 week, and then decreased to baseline control values by 3 weeks. Delaying the period of mobilization until 5 days was not shown to significantly lower the peak WOF value at 1 week, but delaying the period of mobilization until 3 days lowered the peak WOF value at 1 week dramatically to 13%; both the 3- and 5-day delayed-mobilization groups returned to baseline WOF values by 3 weeks. From these data, it can be assumed that there is an early increase in the work necessary for flexion of the injured operated digit and tendon that is present in the immediately mobilized tendons at 3 days and persists to 1 week and that does not appear until 1 week in the immobilized tendons; this rise in WOF can be blunted by delaying the institution of mobilization.

Animals↗

Classification of ulnar deficiency according to the thumb and first web.

Fifty-five ulnar-deficient upper extremities in 45 patients treated at the St. Louis Shriner's Hospital were reviewed in order to evaluate the hand abnormalities. Thumb and first-web abnormalities were noted in 73% of hands. The majority of operations (28 of 53) were recommended to improve functional deficits associated with abnormalities of the thumb and first web. A classification of the ulnar-deficient hand based upon the characteristics of the thumb and first web is presented. When used in combination with any of the six current forearm/elbow classification schemes, this classification more completely describes ulnar deficiency of the upper extremity. Four classification types are proposed based upon progressive involvement of the thumb and first web. In type A, the thumb and first web are normal; in type B, the first web space has mild deficiency and the thumb has mild involvement. Extrinsic tendon function is intact and opposition function is present. In type C, the thumb has varying degrees of involvement. The first web has moderate to severe deficiency, including thumb-index syndactyly, and is often associated with malrotation of the thumb into the plane of the other digits, loss of opposition, and dysfunction of the extrinsic tendons. In type D, the thumb is absent. Previous classifications of ulnar deficiency neglect the radial hand anomalies that have been noted by several authors in a high percentage of affected extremities. Our premise for this classification is that the thumb and first-web abnormalities are related to the complexity of the hand problem and that the frequently noted radial hand abnormalities require the majority of surgical procedures. Such a classification based on the thumb and first-web deformities will focus the surgeon's attention on those deficiencies that are most important for the restoration of function. It is proposed that ulnar deficiency be classified by one of the classification schemes that describes the anatomy of the forearm and/or elbow supplemented by the hand classification type.

Elbow Joint↗