PubMed Health⌕ Search

Biomedical subjects

T Miclau

Publications and source records attributed to T Miclau.

At least 19 recordsLinked to original sources

Cellular and molecular characterization of a murine non-union model.

PURPOSE: We have developed a method to study the molecular and cellular events underlying delayed skeletal repair in a model that utilizes distraction osteogenesis. METHODS: The clinical states of delayed union and non-union were reproduced in this murine model by altering distraction parameters such as the inclusion and exclusion of a latency phase and variations in the rate and rhythm of distraction. Radiographic, cellular, and molecular analyses were performed on the distraction tissues. RESULTS: Eliminating the latency period delayed bony union, but did not appreciably alter the extent of platelet endothelial cell adhesion marker (PECAM) immunostaining. Following elimination of a latency phase and a threefold increase in the rate of distraction, there was a further delay in bone regeneration and a higher rate of non-union (60%). Instead of bone, the distraction gap was comprised of adipose or fibrous tissue. Once again, despite the rigorous distraction protocol, we detected equivalent PECAM staining within the distraction gap. In a minority of cases, cartilage and osseous tissues occupied the distraction gap likely by a prolonged process of endochondral ossification. CONCLUSIONS: Here, we have altered the mechanical environment in such a way to reproducibly create delays in skeletal regeneration. These delays in skeletal tissue regeneration appear to develop even in the presence of endothelial cells, which suggests that mechanisms other than a disruption to the vascular network can account for some cases of non-union.

Animals↗

[Treatment approaches in gunshot injuries of the extremities].

In the view of efficiency and cost effectiveness the increasing incidence of gunshot wounds in Europe demands a modification of treatment protocols. The general basis are debridement of soft tissue injuries, antibiotics and fracture stabilization. The pathology of gunshot wounds and established treatment algorhithms, however have to be adjusted to the ongoing development of gun technology and the thereby caused specific lesions. The treatment of injuries caused by high velocity projectiles necessitates a proactive surgical strategy. Small caliber gunshot wounds can be treated more conservatively. The following review presents an overview on the ballistic and surgical basis for the treatment of gunshot wounds of the musculoskeletal system.

Arm Injuries↗

A minimally invasive medial approach for proximal tibial fractures.

Numerous techniques have been described for MIPPO (minimally invasive percutaneous plate osteosynthesis) for metaphyseal or combined metaphyseal-articular fractures of the proximal tibia. Surgical management is often complicated by the initial soft tissue damage, malalignment, remaining instability, or infection. In this prospective cohort study, we describe the diagnostic procedures vital for preoperative planning. These include plain radiographs and CT scans in case of articular fracture components. The techniques for temporary stabilization and definitive fracture care using 4.5 mm DCP, LC-DCP, and LISS (Less Invasive Stabilization System) by limited medial incisions are described in a stepwise protocol. From 1996 to 1998, six fractures in six patients were studied. According to the AO classification, there were four type 41 fractures and two type 42 fractures. One patient died of ARDS. All patients had an intact medial soft tissue coverage allowing a medial approach. One patient developed a compartment syndrome, which was addressed by lateral dermato-fasciotomy prior to osteosynthesis. A LISS was used in three patients. The only complication related to surgery was in a patient with a four-part fracture with lateral comminution and a dislocated postero-medial fragment, which was reduced and buttressed with a short posteromedial 3.5 mm small fragment plate. This patient developed a deep, intraarticular infection, which was successfully treated with revision surgery; the implants were left in situ. At her latest follow-up at 18 months, she had a range of motion of 0/10/110, was back at work, and able to participate in recreational sports. The average time to healing was between 12 and 20 weeks postoperatively. There was no delayed healing, pseudarthrosis, recurrent fracture or late infection. None of the cases needed bone grafting. At the most recent follow-up, all patients were bearing full weight without walking aids. All cases achieved a neutral alignment and satisfactory range of movement. Though further data are needed we have sound reason to propagate a single medial approach and minimally invasive osteosynthesis as a sufficient and subtle technique for stabilization of these complicated fractures.

Adult↗

Evolution of minimally invasive plate osteosynthesis (MIPO) in the femur.

Problems with conventional open reduction and internal plate fixation of distal femoral fractures are well established. These problems have been associated with extensile exposures of the fracture site. "Biological plating", like intramedullary nail fixation, of distal femoral fractures preserves the soft tissues about the fracture, and is associated with early fracture consolidation and low rates of infection. Anatomical restoration of the articular surface continues to be the main goal in the treatment of these fractures regardless of the stabilization technique. Submuscular plating techniques, which provide for closed reduction of the diaphyseal/metaphyseal component of the fracture, have improved significantly.

Bone Plates↗

Molecular aspects of healing in stabilized and non-stabilized fractures.

Bone formation is a continuous process that is initiated during fetal development and persists in adults in the form of bone regeneration and remodeling. These latter two aspects of bone formation are clearly influenced by the mechanical environment. In this study we tested the hypothesis that alterations in the mechanical environment regulate the program of mesenchymal cell differentiation, and thus the formation of a cartilage or bony callus, at the site of injury. As a first step in testing this hypothesis we produced stabilized and non-stabilized tibial fractures in a mouse model, then used molecular and cellular methods to examine the stage of healing. Using the "molecular map" of the fracture callus, we divided our analyzes into three phases of fracture healing: the inflammatory or initial phase of healing, the soft callus or intermediate stage, and the hard callus stage. Our results show that indian hedgehog(ihh), which regulates aspects of chondrocyte maturation during fetal and early postnatal skeletogenesis, was expressed earlier in an non-stabilized fracture callus as compared to a stabilized callus. ihh persisted in the non-stabilized fracture whereas its expression was down-regulated in the stabilized bone. IHH exerts its effects on chondrocyte maturation through a feedback loop that may involve bone morphogenetic protein 6 [bmp6; (S. Pathi, J.B. Rutenberg, R.L. Johnson, A. Vortkamp, Developmental Biology 209 (1999) 239-253)] and the transcription factor gli3. bmp6 and gli3 were re-induced in domain adjacent to the ihh-positive cells during the soft and hard callus stages of healing. Thus, stabilizing the fracture, which circumvents or decreases the cartilaginous phase of bone repair, correlates with a decrease in ihh signaling in the fracture callus. Collectively, our results illustrate that the ihh signaling pathway participates in fracture repair, and that the mechanical environment affects the temporal induction of ihh, bmp6 and gli3. These data support the hypothesis that mechanical influences affect mesenchymal cell differentiation to bone.

Animals↗

Computed tomography assessment of sacroiliac screw placement relative to the first sacral neuroforamen.

The radiographic interpretation of sacroiliac screws relative to the S1 neuroforamen is difficult for orthopedic surgeons and radiologists. Computed tomography (CT) with axial images alone or combined with multiplanar reconstructions are often used to assess screw position. The reliability, reproducibility, and accuracy of orthopedist and radiologist interpretations of axial CT images with and without multiplanar reconstructions was determined using 24 cadaveric hemipelves with known sacroiliac screw position. Interobserver reliability of determining screw position was fair for orthopedists and slight for radiologists regardless of imaging modality or screw composition. Intraobserver reproducibility was moderate for orthopedists regardless of imaging modality or screw type. Reproducibility among radiologists was moderate using axial images of titanium screws and substantial with addition of multiplanar reconstructions. Overall accuracy was similar for orthopedists and radiologists. CT images with multiplanar reconstructions improve accuracy in determining sacroiliac screw position, but not significantly. Current imaging modalities are limited by large inaccuracies and by interobserver and intraobserver variation.

Aged↗

Posterior lateral mass plate fixation of the cervical spine.

Historically, posterior fixation and fusion have been the most popular method of internally stabilizing the cervical spine after injury. Although techniques such as wiring are effective for most injuries, these methods are inadequate in the absence of intact posterior elements or extension and rotation injuries. We review the indications and techniques for posterolateral mass plate fixation that are useful in these difficult fractures.

Bone Plates↗

Does adult fracture repair recapitulate embryonic skeletal formation?

Bone formation is a continuous process that begins during fetal development and persists throughout life as a remodeling process. In the event of injury, bones heal by generating new bone rather than scar tissue; thus, it can accurately be described as a regenerative process. To elucidate the extent to which fetal skeletal development and skeletal regeneration are similar, we performed a series of detailed expression analyses using a number of genes that regulate key stages of endochondral ossification. They included genes in the indian hedgehog (ihh) and core binding factor 1 (cbfa1) pathways, and genes associated with extracellular matrix remodeling and vascular invasion including vascular endothelial growth factor (VEGF) and matrix metalloproteinase 13 (mmp13). Our analyses suggested that even at the earliest stages of mesenchymal cell condensation, chondrocyte (ihh, cbfa1 and collagen type II-positive) and perichondrial (gli1 and osteocalcin-positive) cell populations were already specified. As chondrocytes matured, they continued to express cbfa1 and ihh whereas cbfa1, osteocalcin and gli1 persisted in presumptive periosteal cells. Later, VEGF and mmp13 transcripts were abundant in chondrocytes as they underwent hypertrophy and terminal differentiation. Based on these expression patterns and available genetic data, we propose a model where Ihh and Cbfa1, together with Gli1 and Osteocalcin participate in establishing reciprocal signal site of injury. The persistence of cbfa1 and ihh, and their targets osteocalcin and gli1, in the callus suggests comparable processes of chondrocyte maturation and specification of a neo-perichondrium occur following injury. VEGF and mmp13 are expressed during the later stages of healing, coincident with the onset of vascularization of the callus and subsequent ossification. Taken together, these data suggest the genetic mechanisms regulating fetal skeletogenesis also regulate adult skeletal regeneration, and point to important regulators of angiogenesis and ossification in bone regeneration.

Aging↗

A mechanical distal aiming device for distal locking in femoral nails.

Although the free hand technique remains the most popular method for distal interlocking screw insertion, proximally mounted radiation independent devices that compensate for implant deformation recently have been developed for the femur. However, the benefits of such systems have not been determined. This study prospectively compared the duration of the nailing procedure, the length of radiation time, and the accuracy of interlocking screw placement when using a radiation independent distal aiming system with those using the free hand technique. In 20 paired intact anatomic specimen femurs, one surgeon experienced only in the free hand technique performed statically locked intramedullary nailing using the two methods. For the aiming system and free hand technique, respectively, the total operation time was 19.1 +/- 8.4 minutes versus 20.9 +/- 11.3 minutes, the distal locking time was 6.6 +/- 2.4 minutes versus 4.8 +/- 1.5 minutes, the total fluoroscopy time was 23 +/- 17 seconds versus 69 +/- 34 seconds, and the distal locking fluoroscopy time was 0 versus 37 +/- 15.5 seconds. There were no failures in either group. Drill nail contact and distal screw damage were greater with the free hand technique. This study suggests that the main advantages of the aiming arm compared with the free hand technique include the elimination of radiation during distal interlocking and more precise screw placement with decreased insertion related hardware damage.

Aged↗

Minimally invasive plate osteosynthesis: does percutaneous plating disrupt femoral blood supply less than the traditional technique?

OBJECTIVES/HYPOTHESIS: Proximal and distal femur fractures have traditionally been treated with open reduction and internal fixation through a standard lateral approach. New, "minimally invasive" internal fixation techniques, however, have been developed in an effort to devascularize the bone less than the traditional method. The purpose of this study was to determine whether a minimally invasive percutaneous plating technique better preserves bone vascularity relative to the traditional method by comparing the effect of the two approaches on the blood supply of the distal femur using silicone arterial dye injection in a cadaveric model. STUDY DESIGN/METHODS: Ten fresh human cadavers underwent lateral conventional plate osteosynthesis (CPO) through a standard lateral approach on one side and minimally invasive plate osteosynthesis (MIPO) through two three-centimeter incisions on the contralateral side. After injection of silicone dye, a dissection was performed bilaterally to identify the femoral perforating and nutrient arteries. RESULTS: All MIPO specimens showed intact perforating and nutrient arteries, whereas the CPO specimens had a variable incidence of vessel disruption. The MIPO group demonstrated better periosteal perfusion in each of the cadavers and improved medullary perfusion in 70 percent of the MIPO specimens compared with the CPO specimens. CONCLUSION: A percutaneous minimally invasive plating technique disrupts the femoral blood supply less than the traditional open method. Such minimally invasive methods may be more advantageous biologically than the traditional method.

Aged↗

The mechanical effect of blocking screws ("Poller screws") in stabilizing tibia fractures with short proximal or distal fragments after insertion of small-diameter intramedullary nails.

OBJECTIVES/HYPOTHESIS: To evaluate the mechanical effects of medial and lateral blocking screws in supplementing intramedullary nail fixation of high proximal and low distal tibial fractures treated with small-diameter intramedullary nails. STUDY DESIGN: Intact fresh human cadaveric tibiae were sectioned to provide ten distal segments measuring seventy millimeters and ten proximal segments measuring ninety millimeters. In the distal segments, stainless steel solid eight-millimeter tibial nails were advanced to eight millimeters from the ankle joint. Two transverse and one anterior-posterior (AP) locking screw were inserted using a custom-made jig. The same jig was used for the placement of a medial and a lateral blocking screw (BS) in the AP direction, nine millimeters above the superior most interlocking screw and eight millimeters distal to the lower end of the segment. In the proximal segments, two interlocking screws (both static and dynamic screws) were placed in a medial-lateral direction with the use of the insertion handle. A jig was used for placement of a medial and a lateral BS in the AP direction, nine millimeters below the lower transverse interlocking screw and sixteen millimeters proximal to the lower end of the segment. The bone-implant construct (BIC) was embedded and fixed in a materials testing machine. The BICs were loaded in the medial-lateral direction at a distance of 185 millimeters from the nail ends with loads from -150 newtons to + 150 newtons. Force-displacement curves were recorded before and after insertion of the BSs. RESULTS: In proximal BICs, the addition of BSs decreased the deformation of the BICs 25 percent, from 8.9 +/- 1.9 degrees [mean +/- standard deviation (SD)] in the control group to 6.8 +/-1.1 degrees in the BS group (mean +/- SD) (p < 0.0001). In distal BICs, the addition of BSs decreased the deformation of the BICs 57 percent, from 9.5 +/- 1.4 degrees (mean +/- SD) in the control group to 4.0 +/- 1.0 degrees in the BS group (mean +/- SD) (p < 0.0001). CONCLUSIONS: The study suggests that medial and lateral blocking screws can increase the primary stability of distal and proximal metaphyseal fractures after nailing and can be an effective tool for selected cases that exhibit malalignment and/or instability.

Aged↗

The use of Poller screws as blocking screws in stabilising tibial fractures treated with small diameter intramedullary nails.

Intramedullary nailing of metaphyseal fractures may be associated with deformity as a result of instability after fixation. Our aim was to evaluate the clinical use of Poller screws (blocking screws) as a supplement to stability after fixation with statically locked intramedullary nails of small diameter. We studied, prospectively, 21 tibial fractures, 10 in the proximal third and 11 in the distal third in 20 patients after the insertion of Poller screws over a mean period of 18.5 months (12 to 29). All fractures had united. Healing was evident radiologically at a mean of 5.4+/-2.1 months (3 to 12) with a mean varus-valgus alignment of -1.0 degree (-5 to 3) and mean antecurvatum-recurvatum alignment of 1.6 degrees (-6 to 11). The mean loss of reduction between placement of the initial Poller screw and follow-up was 0.5 degrees in the frontal plane and 0.4 degrees in the sagittal plane. There were no complications related to the Poller screw. The clinical outcome, according to the Karström-Olerud score, was not influenced by previous or concomitant injuries in 18 patients and was judged as excellent in three (17%), good in seven (39%), satisfactory in six (33%), fair in one (6%), and poor in one (6%).

Adolescent↗

The topography of the perforating vessels of the deep femoral artery.

This study evaluated the anatomic relationship between the femur and the vessels that arise from the deep femoral artery, that is, the perforating arteries and the nutrient artery. Blue silicone dye was injected through the common femoral artery in 20 fresh human cadavers. An anteromedial and a posterolateral dissection were performed to identify the femoral perforating arteries and the nutrient artery of the femur. The length of the femur and the distances between the tip of the greater trochanter and the perforating arteries and nutrient artery were measured. This study showed that a reliable, clinically applicable topographic relationship exists between the femur and the perforating arteries and the nutrient artery.

Aged↗

Common molecular pathways in skeletal morphogenesis and repair.

The formation of bone is a continual process in vertebrate development, initiated during fetal development and persisting in adulthood in the form of remodeling and repair. The remarkable capacity of skeletal tissues to regenerate has led to the hypothesis that the molecular signaling pathways regulating skeletogenesis are shared during fetal development and adult wound healing. A number of key regulatory pathways that are required for endochondral ossification during fetal development are described, and their reintroduction in fracture repair demonstrated. Secreted proteins such as Sonic and Indian hedgehog exert their effect on pattern formation and chondrogenesis in the appendicular skeleton, partly through regulation of molecules such as bone morphogenic proteins (Bmps) and parathyroid hormone-related peptide (PTHrP). Once chondrocytes have matured and hypertrophied, they undergo apoptosis and are replaced by bone; the transcription factor Cbfal plays a critical role in this process of chondrocyte differentiation and ossification. Analyses of the expression patterns of these genes during fracture healing strongly suggest that they play equivalent roles in adult wound repair. Knowledge acquired through the study of fetal skeletogenesis will undoubtedly contribute to an understanding of fracture repair, and subsequently guide the development of biologically based therapeutic interventions.

Animals↗

Imaging assessment of sacroiliac screw placement relative to the neuroforamen.

STUDY DESIGN: Twenty-four cannulated sacroiliac screws were placed bilaterally into 12 cadaveric pelvi (12 titanium screws and 12 stainless-steel screws) and were imaged using conventional and multiplanar reconstructed computed tomography. OBJECTIVES: To determine whether sacroiliac screw position assessment relative to the neuroforamen is enhanced by: 1) computed tomography using multiplanar reconstructions and 2) the use of titanium screws rather than stainless-steel screws. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, there have been no prior studies demonstrating the accuracy of multiplanar computed tomography compared with that of conventional (axial) tomography in determining the position of sacroiliac screws relative to the neuroforamen. Although titanium screws have been shown to have less scatter than stainless-steel screws, the effect of alloy composition on the radiographic accuracy of interpreting the screw position relative to the sacral neuroforamen is unknown. METHODS: Screws were deliberately placed into: position A, in which the screw did not violate the neuroforamen; position B, in which the threads of the screw came within 3 mm of the neuroforamen; and position C, in which the screw clearly was nearly centered in the neuroforamen. The degrees of accuracy in assessing screw position relative to the neuroforamen using conventional (axial) images and using multiplanar reconstructed images were compared. RESULTS: The axial images were accurate in determining screw position relative to the neuroforamen in 50% of cases in which titanium screws were used and in 42% of cases in which stainless-steel screws were used. The corresponding values for multiplanar reconstructions were 92% for cases in which titanium screws were used and 67% for cases in which stainless-steel screws were used. The accuracy of multiplanar reconstructions was statistically better than that of axial images (P < 0.05). Metallic scatter was increased in stainless-steel screws. CONCLUSIONS: The results of this study suggest that the use of computed tomography with multiplanar reconstruction improves accuracy in determining sacroiliac screw position relative to the neuroforamen. The assessment of screw position may be facilitated using titanium screws.

Aged↗

Effect of ciprofloxacin on the proliferation of osteoblast-like MG-63 human osteosarcoma cells in vitro.

Locally applied antibiotic therapy is gaining popularity for the treatment of infections associated with open fractures and posttraumatic osteomyelitis. With use of local techniques, ciprofloxacin levels as high as 1,300 microg/ml, or over 200 times the bone levels achieved with intravenous administration, have been reported. To study the possible effects of ciprofloxacin on bone, osteoblast-like cells from the MG-63 human osteosarcoma cell line were studied. The cells were grown in antibiotic-free media and exposed to concentrations of ciprofloxacin at 0, 10, 100, 200, and 1,000 microg/ml to establish an initial dose-response curve. Media containing the appropriate dose of ciprofloxacin were changed every 24 hours. Cell number and [3H]thymidine incorporation per cell were determined at 0, 24, and 72 hours. A second dose-response curve was performed at concentrations of 0, 10, 20, 40, and 80 microg/ml. Three experiments, each with four observations, were performed. The results of this study demonstrated that ciprofloxacin caused significant decreases (p < 0.05) in cell number at 40 microg/ml at 24 hours and 20 microg/ml at 72 hours. [3H]thymidine incorporation per cell decreased significantly at levels of 80 microg/ml at 24 hours and 20 microg/ml at 72 hours. The authors conclude that reported local levels of ciprofloxacin seen in vivo inhibit the proliferation of human osteoblast-like cells in vitro.

Anti-Infective Agents↗

Deformation of femoral nails with intramedullary insertion.

Current methods of distal interlocking of intramedullary femoral nails are dependent on image intensification. However, radiation exposure to the patient, the operating room staff, and the surgeon remains a concern. Proximally mounted, radiation-free aiming systems for distal interlocking of femoral nails have reportedly failed because of nail deformation with insertion. To better understand this deformation, a three-dimensional magnetic motion tracking system was used to determine the position of the distal interlocking hole following nail insertion. The amount and direction of deformation of commercially available small-diameter implants (unslotted 9-mm nails inserted without reaming) and large-diameter implants (slotted 13-mm nails inserted with reaming) from a single manufacturer were analyzed. Measurements of deformation (three translations and three angles), based on the center of the distal transverse locking hole, were performed on 10 paired intact human cadaveric femora before and after insertion. The technique produced the following results for the small and large-diameter nails, respectively: lateral translations of 18.1+/-10.0 mm (mean+/-SD, range: 47.8 mm) and 21.5+/-7.9 mm (range: 26.4 mm), dorsal translations of -3.1+/-4.3 mm (range: 15.2 mm) and 0.4+/-9.8 mm (range: 30.1 mm), and rotation about the longitudinal axes of -0.1+/-0.2 degrees (range: 0.7 degrees) and 10.0+/-3.1 degrees (range: 7.8 degrees). This technique is useful for measuring insertion-related femoral nail deformation. The data for the nails tested suggest that a simple aiming arm, mounted on the proximal end of the femoral nail alone, will not sufficiently provide accurate distal aiming.

Bone Nails↗

A new mechanical aiming device for the placement of distal interlocking screws in femoral nails.

Although the free-hand technique remains the most popular method for distal interlocking screw insertion, a proximally mounted "radiation-independent" device which compensates for implant deformation has been developed. In 15 intact human cadaveric femora the same surgeon performed statically locked intramedullary nailing using the distal aiming system. Operation time, distal screw insertion, total radiation time and accuracy of the interlocking screw placement were measured using a radiation-independent distal aiming system. The average total operation time was 21.2+/-8.6 min, and the average distal locking time (2 screws) was 7.1+/-2.4 min. The total operation time and the distal locking time declined over the first 10 cases. These times did not significantly improve in the subsequent 5 procedures. The average total fluoroscopy time was 28.1+/-16.6 s. None of the screw placements using the distal aiming device required the use of fluoroscopy. Drill-nail contact was absent in 5 drillings, mild in 9 drillings, moderate in 16 drillings, and severe in none. Measurement of screw damage showed in 55 of 60 measurements wear of less than 15 microm. There were no failures or major complications. A minor complication related to distal locking was observed in one specimen. This study suggests that distal interlocking screws can be placed successfully using a radiation-independent aiming arm-based system, which accounts for nail deformations. The distal aiming device (DAD) can be learned easily. The main advantages of the aiming arm include the elimination of radiation during distal interlocking and precise screw placement with little insertion-related hardware damage.

Aged↗