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Biomedical subjects

Michael Leunig

Publications and source records attributed to Michael Leunig.

At least 19 recordsLinked to original sources
PubMed2006

Sequential changes in vessel formation and micro-vascular function during bone repair.

BACKGROUND: Angiogenesis, the process of new vessel formation from a pre-existing vascular network, is essential for bone development and repair. New vessel formation and microvascular functions are crucial during bone repair, not only for sufficient nutrient supply, transport of macromolecules and invading cells, but also because they govern the metabolic microenvironment. Despite its central role, very little is known about the initial processes of vessel formation and microvascular function during bone repair. METHODS: To visualize and quantify the process of vessel formation and microvascular function during bone repair, we transplanted neonatal femora with a substantial defect into dorsal skin-fold chambers in severe combined immunodeficient (SCID) mice for continuous noninvasive in-vivo evaluation. We employed intravital microscopic techniques to monitor effective microvascular permeability, functional vascular density, blood flow rate and leukocyte flux repeatedly over 16 days. Oxytetracyclin and v. Kossa/v. Giesson staining was performed to quantify the calcification process in vivo and in vitro. RESULTS: Development of a hematoma surrounding the defect area was the initial event, which was accompanied by a significant increase in microvascular permeability and blood flow rate. With absorption of the hematoma and vessel maturation, permeability decreased continuously, while vascular density and tissue perfusion increased. Histological evaluation revealed that the remodeling of the substantial defect prolonged the in-vivo monitored calcification process. INTERPRETATION: The size of the initial substantial defect correlated positively with increased permeability, suggesting improved release of permeability-inducing cytokines. The unchanged permeability in the control group with boiled bones and a substantial defect corroborated these findings. The adaptation to increasing metabolic demands was initially mediated by increased blood flow rate, later with increasing vascular density through increased tissue perfusion rate. These insights into the sequence of microvascular alterations may assist in the development of targeted drug delivery therapies and caution against the use of permeability-altering drugs during bone healing.

Animals↗
PubMed2006

Comparison of six radiographic projections to assess femoral head/neck asphericity.

UNLABELLED: Early radiographic detection of femoroacetabular impingement might prevent initiation and progression of osteoarthritis. The structural abnormality in femoral-induced femoroacetabular impingement (cam type) is frequently asphericity at the anterosuperior head/neck contour. To determine which of six radiographic projections (anteroposterior, Dunn, Dunn/45 degrees flexion, cross-table/15 degrees internal rotation, cross-table/neutral rotation, and cross-table/15 degrees external rotation) best identifies femoral head/neck asphericity, we studied 21 desiccated femurs; 11 with an aspherical femoral head/neck contour and 10 with a spherical femoral head/neck contour. To radiographically quantify femoral head asphericity, we measured the angle where the femoral head/neck leaves sphericity (angle alpha). The aspherical femoral head/neck contours had a greater maximum angle alpha (70 degrees ) compared with the spherical head/neck contours (50 degrees ). The angle alpha varied depending on the radiographic projection: it was greatest in the Dunn view with 45 degrees hip flexion (71 degrees +/- 10 degrees ) and least in the cross-table view in 15 degrees external rotation (51 degrees +/- 7 degrees ). Diagnosis of a pathologic femoral head/neck contour depends on the radiologic projection. The Dunn view in 45 degrees or 90 degrees flexion or a cross-table projection in internal rotation best show femoral head/neck asphericity, whereas anteroposterior or externally rotated cross-table views are likely to miss asphericity. LEVEL OF EVIDENCE: Prognostic study, level II-1 (retrospective study).

Female↗
PubMed2006

Treatment of femoro-acetabular impingement: preliminary results of labral refixation.

BACKGROUND: Recent advances in the understanding of the anatomy and function of the acetabular labrum suggest that it is important for normal joint function. We found no available data regarding whether labral refixation after treatment of femoro-acetabular impingement affects the clinical and radiographic results. METHODS: We retrospectively reviewed the clinical and radiographic results of fifty-two patients (sixty hips) with femoro-acetabular impingement who underwent arthrotomy and surgical dislocation of the hip to allow trimming of the acetabular rim and femoral osteochondroplasty. In the first twenty-five hips, the torn labrum was resected (Group 1); in the next thirty-five hips, the intact portion of the labrum was reattached to the acetabular rim (Group 2). At one and two years postoperatively, the Merle d'Aubigné clinical score and the Tönnis arthrosis classification system were used to compare the two groups. RESULTS: At one year postoperatively, both groups showed a significant improvement in their clinical scores (mainly pain reduction) compared with their preoperative values (p = 0.0003 for Group 1 and p < 0.0001 for Group 2). At two years postoperatively, 28% of the hips in Group 1 (labral resection) had an excellent result, 48% had a good result, 20% had a moderate result, and 4% had a poor result. In contrast, in Group 2 (labral reattachment), 80% of the hips had an excellent result, 14% had a good result, and 6% had a moderate result. Comparison of the clinical scores between the two groups revealed significantly better outcomes for Group 2 at one year (p = 0.0001) and at two years (p = 0.01). Radiographic signs of osteoarthritis were significantly more prevalent in Group 1 than in Group 2 at one year (p = 0.02) and at two years (p = 0.009). CONCLUSIONS: Patients treated with labral refixation recovered earlier and had superior clinical and radiographic results when compared with patients who had undergone resection of a torn labrum. Although the results must be considered preliminary, we now recommend refixation of the intact portion of the labrum after trimming of the acetabular rim during surgical treatment of femoro-acetabular impingement.

Acetabulum↗
PubMed2006

Nonarthroplasty surgical treatment of hip osteoarthritis.

The two conditions that give rise to osteoarthritis of the hip are dysplasia and nondysplasia. Dysplasia, commonly associated with anterolateral acetabular deficiency, may lead to osteoarthritis in 40% of patients in the United States with this condition. In a distinct category of patients with so-called idiopathic arthritis, there is no apparently identifiable cause for osteoarthritis. There is emerging evidence that subtle morphologic abnormalities around the hip, resulting in femoroacetabular impingement, may often be a contributing factor to osteoarthritis in young patients.

Humans↗
PubMed2005

Is hemoglobin in hemoglobin vesicles infused for isovolemic hemodilution necessary to improve oxygenation in critically ischemic hamster skin?

The aim of this study was to test the influence of hemoglobin, encapsulated in phospholipid vesicles as an oxygen carrier, given in the course of isovolemic hemodilution to improve oxygenation in critically ischemic hamster flap tissue. Capillary hemodynamics and macromolecular leakage were investigated with intravital microscopy and analyzed off-line with the CapImage software. Partial tissue oxygen tension was measured with fluorescence quenching electrodes. The occurrence of apoptosis was assessed with the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Vesicles with (HbV) or without (V) encapsulated Hb were suspended in 6% hydroxyethyl starch (HES) used for the 33% blood exchange. In the ischemic tissue, hemodilution led to an increase in functional capillary density by 31% for HES (P < 0.01 vs. other groups), 66% for V-HES, and 62% for HbV-HES (all P < 0.01 vs. control). Capillary diameters behaved inversely proportional to capillary microhemodynamics. The 20% increase in macromolecular leakage found over time in control animals was completely abolished in the vesicles groups (P < 0.01) but not with HES. Oxygen tension was improved from 10.7 to 16.0 mmHg after HbV-HES (P < 0.01 vs. baseline and other groups). Compared with the other groups, apoptosis was significantly reduced after HbV-HES (P < 0.01). We conclude that the encapsulation of Hb was essential to attenuate hypoxia and subsequent cell death in the critically ischemic tissue. However, the effect was partly attributed to the rheological changes exerted by the vesicles.

Acute Disease↗
PubMed2005

Wear particles and surface topographies are modulators of osteoclastogenesis in vitro.

Prosthetic and osteosynthetic implants from metal alloys will be indispensable in orthopedic surgery, as long as tissue engineering and biodegradable bone substitutes do not lead to products that will be applied in clinical routine for the repair of bone, cartilage, and joint defects. Therefore, the elucidation of the interactions between the periprosthetic tissues and the implant remains of clinical relevance and several factors are known to affect the longevity of implants. Within this study, the effects of metal particles and surface topography on the recruitment of osteoclasts was investigated in vitro in a coculture of osteoblasts and bone marrow cells. The cells were grown in the presence of particles of different sizes and chemical composition or on metal discs with polished or sandblasted surfaces, respectively. At the end of the culture, newly formed osteoclasts were counted. Osteoclastogenesis was reduced when particles were added directly to the coculture. The effect depended on the size of the particles, small particles exerting stronger effects than larger ones. The chemical composition of the particles, however, did not affect the development of osteoclasts. In cocultures grown on sandblasted surfaces, osteoclasts developed at higher rates than they did in cultures on polished surfaces. The data demonstrate that wear particles and implant surfaces affect osteoclastogenesis and thus may be involved in the induction of local bone resorption and the formation of osteolytic lesions, leading eventually to the loosening of orthopedic implants.

Animals↗
PubMed2005

Anatomic considerations for the choice of surgical approach for hip resurfacing arthroplasty.

A number of surgical exposures have been advocated over the past 20 years by the pioneers of resurfacing hip arthroplasty and include the anterior, anterolateral, lateral, and posterolateral approaches. Not all of these approaches, however, appear to provide adequate exposure while respecting the local biology that seems to be imperative for the procedure. Based on an anatomic study, the most "bio-logical" surgical approach for hip resurfacing arthroplasty appears to be through a lateral or posterolateral approach using a digastric trochanteric osteotomy combined with an anterior hip dislocation. These exposures avoid injury to the medial femoral circumflex artery supplying the femoral head and allow access and treatment to the commonly observed hip pathologies that are frequently located anteriorly.

Adult↗
PubMed2005

Distribution of vascular foramina around the femoral head and neck junction: relevance for conservative intracapsular procedures of the hip.

Precise knowledge of femoral head vascular anatomy is mandatory for the safe execution of intracapsular surgical procedures aimed at preserving the hip joint. No quantitative topographic data exist concerning the exact location and distribution of the entrance of these vessels through nutrient vascular foramina at the femoral head and neck junction. This study shows that only a few significant retinacular vessels may reach the adult femoral head on its anterior aspect and that most vascular foramina are located close to the antero- and posterosuperior regions of the femoral head and neck junction. This larger segment should be carefully protected during any conservative intracapsular procedure of the hip and may be desirable in femoral head resurfacing arthroplasty.

Arthroplasty, Replacement, Hip↗
PubMed2005

New generation of hemoglobin-based oxygen carriers evaluated for oxygenation of critically ischemic hamster flap tissue.

OBJECTIVES: The aim of this study was to investigate and compare the effects of a traditionally formulated, low-viscosity, right-shifted polymerized bovine hemoglobin solution and a highly viscous, left-shifted hemoglobin vesicle solution (HbV-HES) on the oxygenation of critically ischemic peripheral tissue. DESIGN: Randomized, prospective study. SETTING: University laboratory. SUBJECT: A total of 40 male golden Syrian hamsters. INTERVENTIONS: Island flaps were dissected from the back skin of anesthetized hamsters. The flap included a critically ischemic, hypoxic area that was perfused via a collateralized vasculature. One hour after completion of the preparation, the animals received a 33% blood exchange with 6% hydroxyethyl starch 200/0.5 (HES, n = 9), HbV suspended in HES (HbV-HES, n = 8), or polymerized bovine hemoglobin solution (n = 9). MEASUREMENTS AND MAIN RESULTS: Three hours after the blood exchange, microcirculatory blood flow (laser-Doppler flowmetry) was increased to 262% of baseline for HbV-HES (p < .01) and 197% for polymerized bovine hemoglobin solution (p < .05 vs. baseline and HbV-HES). Partial tissue oxygen tension (bare fiber probes) was only improved after HbV-HES (9.4 torr to 14.2 torr, p < .01 vs. baseline and other groups). The tissue lactate/pyruvate ratio (microdialysis) was elevated to 51 in the untreated control animals, and to 34 +/- 8 after HbV-HES (p < .05 vs. control) and 38 +/- 11 after polymerized bovine hemoglobin solution (not significant). CONCLUSIONS: Our study suggests that in critically ischemic and hypoxic collateralized peripheral tissue, oxygenation may be improved by normovolemic hemodilution with HbV-HES. We attributed this improvement to a better restoration of the microcirculation and oxygen delivery due to the formulation of the solution.

Animals↗
PubMed2005

Fibrocystic changes at anterosuperior femoral neck: prevalence in hips with femoroacetabular impingement.

PURPOSE: To retrospectively evaluate if there is an association between juxta-articular fibrocystic changes at the anterosuperior femoral neck and femoroacetabular impingement (FAI). MATERIALS AND METHODS: The institutional review board approved this study and did not require informed patient consent. An orthopedic surgeon and a radiologist in consensus retrospectively reviewed the anteroposterior (AP) pelvic radiographs of 117 hips with FAI and compared these images with the AP radiographs of a control group of 132 hips with developmental dysplasia (DD) to determine the prevalence of juxta-articular fibrocystic changes at the anterosuperior femoral neck. Criteria for juxta-articular fibrocystic changes at the anterosuperior femoral neck were location close to the physis and a diameter (of the fibrocystic change) of greater than 3 mm. The sensitivity and specificity of AP pelvic radiography in the detection of these fibrocystic changes were calculated by using an additional 61 hips with FAI and on the basis of findings at magnetic resonance (MR) arthrography, which was routinely performed for assessment of FAI. In 24 patients who underwent joint-preserving surgery for FAI, the fibrocystic changes were localized intraoperatively and the spatial relation of the region of these changes to the area of FAI was identified. Joint-preserving surgery consisted of anterior surgical dislocation of the hip with osteochondroplasty of the proximal femur and/or the acetabular rim to improve the impingement-free range of hip motion. For statistical comparisons, nonparametric tests were performed. RESULTS: Fibrocystic changes were identified on the AP radiographs of 39 (33%) of the 117 FAI-affected hips and on none of the radiographs of the 132 DD-affected hips. According to MR arthrogram findings, the sensitivity, specificity, and positive and negative predictive values of AP pelvic radiography were 64%, 93%, 91%, and 71%, respectively. The mean diameter of the juxta-articular fibrocystic changes was 5 mm (range, 3-15 mm); smaller lesions were more prevalent. Dynamic MR imaging with the hip flexed and intraoperative observations revealed a close spatial relationship between the region of the fibrocystic changes at the anterosuperior femoral neck and the acetabular rim. CONCLUSION: The high prevalence of juxta-articular fibrocystic changes at the anterosuperior femoral neck and their spatial relation to the impingement site suggest an association and possible causal relationship between these alterations and FAI.

Acetabulum↗
PubMed2005

The influence of trauma and ischemia on carbohydrate metabolites monitored in hamster flap tissue.

To monitor hypoperfusion of the peripheral tissues in critical illness caused by injury, we measured the concentrations of glucose, pyruvate, and lactate in traumatized and ischemic hamster flap tissue with the use of microdialysis. The interruption of the anatomic blood supply led to a drastic decrease in microvascular blood flow (laser Doppler flowmetry) and partial tissue oxygen tension (dye fluorescence quenching technique) in the ischemic part of the flap (both P < 0.01). In the traumatized area, blood flow, oxygen tension, and pyruvate were similar to the healthy control tissue throughout the experiments, whereas pyruvate was reduced in the ischemic tissue (P < 0.05 versus baseline and other tissues). Lactate was increased in both parts of the flap (P < 0.01 versus baseline and other groups for ischemic, not significant for traumatized). The sensitivity to detect ischemic hypoxia was 62% for lactate and 93% for lactate/pyruvate ratio (L/P) (P < 0.01). The specificity to discern ischemia-related from trauma-related changes was 71% for lactate and 70% for L/P (not significant). Our results suggest that L/P is more accurate than lactate for monitoring ischemia-related hypoxia after trauma. However, the rate of increased values originating from normally perfused but traumatized tissue was high for both markers.

Animals↗
PubMed2004

Advancement of the vastus lateralis muscle for the treatment of hip abductor discontinuity.

Impaired abductor function of the hip resulting from a discontinuous gluteus medius often is encountered in revision hip surgery. If the gluteus medius can be reattached to the proximal femur, functional results are satisfactory. If this is not possible, it would be desirable to restore the continuity of the gluteus medius by bridging the defect with local tissue. An anatomic study was performed in 15 cadavers, and proximal advancement of the vastus lateralis without injury to the neurovascular pedicle was 8 cm (range, 7-10 cm). Clinically, the technique was used in 3 patients. At follow-up, both living patients walked without a cane and both were able to hold the leg abducted against moderate pressure. Proximal advancement of the vastus lateralis can successfully bridge defects of the gluteus medius and partially restores abductor function.

Adult↗
PubMed2004

Potential role of pre-existing blood vessels for vascularization and mineralization of osteochondral grafts: an intravital microscopic study in mice.

BACKGROUND: The aim of this study was to develop an experimental model that allows to elude the potential role of the preexisting graft microvasculature for vascularization and mineralization of osteochondral grafts. ANIMALS AND METHODS: For that purpose, the II-IV metatarsals of fetal DDY-mice known to be nonvascularized at day 16 of gestation (M16) but vascularized at day 18 (M18) were freshly transplanted into dorsal skin fold chambers of adult DDY mice. Using intravital microscopy angiogenesis, leukocyte-endothelium interaction and mineralization were assessed for 12 days. RESULTS: Angiogenesis occurred at 32 hours in M18, but not before 57 hours in M16 (p = 0.002), with perfusion of these vessels at 42 hours (p = 0.005) and 65 hours (p = 0.1), respectively. Vessels reached a density three times as high as that of the recipient site at day 6, remaining constant until day 12 in M18, whereas in M16 vascular density increased from day 6 and reached that of M18 at day 12 (p = 0.04). Leukocyte-endothelium interaction showed sticker counts elevated by a factor of 4-5 in M18 as compared to M16. Mineralization of osteochondral grafts did not differ between M16 and M18, which significantly increased in both groups throughout the observation period. INTERPRETATION: We propose the faster kinetics in the angiogenic response to M18 and the elevated counts of sticking leukocytes to rest on the potential of establishing end-to-end anastomoses (inosculation) of the vascularized graft with recipient vessels.

Animals↗
PubMed2004

Magnetic resonance arthrography of labral disorders in hips with dysplasia and impingement.

Despite the fact that classic studies on osteoarthritis of the hip have shown the periphery of the hip to be prone to degeneration, it was not until recently that an abnormal acetabular labrum has been associated with osteoarthritis. This study was designed to determine whether magnetic resonance arthrography can show differences in disorders of the labrum (tears, size, ganglion formation) expected in symptomatic patients with developmental dysplasia of the hip and anterior femoroacetabular impingement. Fourteen patients in each group were evaluated preoperatively not only clinically but also with conventional radiographs and magnetic resonance arthrographs. In both conditions, disorders of the labrum localized identically with a predilection to the anterosuperior quadrant of the acetabulum. Labral tears were observed in nine hips of each group. The labrum was enlarged in 12 hips with dysplasia but in none of the hips with impingement. Ganglion formation in the periacetabular area was seen in 10 hips with dysplasia and three hips with impingement. These findings provide evidence that the anterosuperior acetabulum represents the initial fatiguing site of the hip under both conditions. Based on these data, the size of the labrum and the presence of soft tissue ganglia seem to be good predictors for the presence of developmental dysplasia, whereas the presence of tears did not differentiate between conditions. The capability of magnetic resonance arthrography to show these differences in labral disorders suggests this method is a helpful diagnostic tool that can aid in defining the most appropriate treatment strategy.

Adolescent↗
PubMed2004

Femoroacetabular impingement as a factor in the development of nonunion of the femoral neck: a report of three cases.

OBJECTIVES: Description of an anatomic condition where a femoroacetabular impingement was identified as the cause for the development of nonunion of the femoral neck. DESIGN: Retrospective analysis. SETTING: University hospital. PATIENTS: Three patients, aged 27 to 74 years, in whom, after exclusion of other known factors, a femoroacetabular impingement was identified as the cause for the nonunion of a femoral neck fracture. INTERVENTION: Surgical correction of the femoroacetabular impingement. MAIN OUTCOME MEASUREMENT: Intraoperative verification of femoroacetabular impingement. Healing of the femoral neck non-union. RESULTS: In all 3 patients, femoroacetabular impingement was confirmed at surgery. After elimination of the cause for impingement, all nonunions went on to uneventful healing. CONCLUSIONS: A femoroacetabular impingement mechanism is proposed as a cause for nonunion of femoral neck fractures. Predisposing factors such as bulging at the fracture site or decreased femoral-neck offset should be addressed at the time of initial fracture treatment.

Adult↗
PubMed2004

Histopathologic features of the acetabular labrum in femoroacetabular impingement.

This paper summarizes clinical and histopathologic findings derived from 25 patients who had surgery for symptomatic femoroacetabular impingement. We explored if observed pathologic features were consistent with hypothesized mechanisms of injury, if severity of osteoarthritis and labral degeneration were associated, and if labral refixation would present an alternative. Clinically, all patients presented with limited range of motion at the hip attributable to pain and a positive impingement test. Magnetic resonance arthrography and surgical observations showed degenerated or ruptured labra or both in the anterior and/or superior regions of the acetabular rim (24 of 25 specimens) which correlated with pain provocation, limited range of motion, and anatomic deformities. Histologically, labra were mostly hyperplastic with disorganized cystic matrices. No inflammation was observed. Spatial distribution of degenerated labral matrices was not different for the two femoroacetabular impingement mechanisms. Labral degeneration and severity of osteoarthritis observed on radiographs did not correlate. In patients having only joint debridement, the labral matrix at the tip, near its vascular supply, was normal. Femoroacetabular impingement is a gentle chronic irritation of the labra located at the site of rupture that elicits a degenerative reaction. In early stages of the disease, the labral tip is not involved, providing the possibility of labral refixation after resection of the degenerated portion.

Acetabulum↗
PubMed2004

The avascular talus: revascularization in an animal model.

Avascular necrosis of bone such as the talus can lead to collapse and loss of function. To avoid this, early revascularization has been proposed as an important event. Revascularization can occur either by vessel growth directly through the bony surface, or by vessel growth into the periosteum or ligaments with secondary reconnection to the bone. The ability to attract new vessels (angiogenesis) of the bony surface and the connective tissue was compared in an animal model. A talus isograft (all cortical surface, periosteum, and ligaments remaining; n = 11) or a sector of a femoral head isograft (cancellous surface, no connective tissue; n = 12) of adult mice was implanted into dorsal skinfold chambers of mice of the same strain. The implants were observed by intravital microscopy every 12 hours. First indicators of angiogenesis were hemorrhages around the implants (tali: 11 of 11, 72 +/- 12 hours; femoral heads: 6 of 12, 84 +/- 24 hours). Next, a sudden redness of the transplant indicated marrow hemorrhage (tali: 9 of 11 after 84 +/- 36 hours; femoral heads: 10 of 12 after 96 +/- 36 hours). Histology showed clear growth of capillaries into the cancellous surface of the femoral heads and possible growth of capillaries into the ligament stumps (tali). However, there was widespread necrosis of the marrow cells indicating failure of recirculation. A cancellous bony surface as well as the soft tissues attached to the bone provided a stimulus to rapid revascularization of the grafts. This model was able to evaluate differing rates of early partial revascularization for various bone surfaces, which may have implications for studying treatment options for certain fracture dislocations (e.g., in the talus).

Animals↗