Norbert P. Haas

Musculo-skeletal loading conditions at the hip during walking and stair climbing

Musculo-skeletal loading plays an important role in the primary stability of joint replacements and in the biological processes involved in fracture healing. However, current knowledge of musculo-skeletal loading is still limited. In the past, a number of musculo-skeletal models have been developed to estimate loading conditions at the hip. So far, a cycle-to-cycle validation of predicted musculo-skeletal loading by in vivo measurements has not been possible. The aim of this study was to determine the musculo-skeletal loading conditions during walking and climbing stairs for a number of patients and compare these findings to in vivo data. Following total hip arthroplasty, four patients underwent gait analysis during walking and stair climbing. An instrumented femoral prosthesis enabled simultaneous measurement of in vivo hip contact forces. On the basis of CT and X-ray data, individual musculo-skeletal models of the lower extremity were developed for each patient. Muscle and joint contact forces were calculated using an optimization algorithm. The calculated peak hip contact forces both over- and under-estimated the measured forces. They differed by a mean of 12% during walking and 14% during stair climbing. For the first time, a cycle-to-cycle validation of predicted musculo-skeletal loading was possible for walking and climbing stairs in several patients. In all cases, the comparison of in vivo measured and calculated hip contact forces showed good agreement.Thus, the authors consider the presented approach as a useful means to determine valid conditions for the analysis of prosthesis loading, bone modeling or remodeling processes around implants and fracture stability following internal fixation.

Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats

Antibiotic prophylaxis is a routine procedure in orthopedic surgery. Various local antibiotic delivery techniques are used to reduce bone- and soft tissue-related infection. The objective of this study was to evaluate the efficacy of a new biodegradable, gentamicin-loaded poly(D,L-lactide) (PDLLA) coating of orthopedic devices in preventing implant-related osteomyelitis. The medullary cavities of tibiae in 30 Sprague Dawley rats were contaminated with Staphylococcus aureus (10(3) colony forming units). Simultaneously titanium Kirschner wires, uncoated (group II), coated with PDLLA (group III), or coated with PDLLA + 10% gentamicin (group IV), were implanted. Ten animals that received phosphate-buffered saline and uncoated Kirschner wires served as controls (group I). Follow-up was 6 weeks. In weekly intervals X-rays of the tibiae were performed, blood counts were taken, and body temperature and weight were determined. After sacrifice infection was evaluated by histological and microbiological analysis. All animals of groups II and III developed microbiological, histological, and radiological signs of infection, including osseous destruction and soft tissue swelling. All animals of the control group remained sterile. Cultures of implants of group IV showed significantly reduced bacterial growth compared to cultures of groups II and III, and three implants of group IV remained sterile. Further radiological and histological signs of infection were significantly reduced in the gentamicin-coated group compared to groups II and III. No significant differences in body weight, body temperature, and blood parameters between all groups were observed. Local application of antibiotic-coated orthopedic devices containing PDLLA and 10% gentamicin significantly reduced implant-related infection in this animal model.

Quantitative assessment of growth factors in reaming aspirate, iliac crest, and platelet preparation ☆

Large bony defects and non-unions are still a complication in trauma and orthopedic surgery. Treatment strategies include the use of autogenous materials (iliac crest), allogenic bone, bone substitutes, and currently stimulation with growth factors such as BMP-2, BMP-7 or the growth factors containing platelet-rich plasma (PRP). Another source of bone graft material might be the cuttings produced during intramedullary reaming. The aim of this study was to compare the quantity of various growth factors found within iliac crest, bony reaming debris, reaming irrigation fluid, and platelet-rich plasma. Iliac crest and reaming debris and irrigation samples were harvested during surgery. PRP was prepared from blood. The growth factors in the bony materials (iliac crest or reaming debris) and of the liquid materials (platelet-poor plasma (PPP), platelet-rich plasma (PRP) or reaming irrigation) were compared. Elevated levels of FGFa, PDGF, IGF-I, TGF-beta1 and BMP-2 were measured in the reaming debris as compared to iliac crest curettings. However, VEGF and FGFb were significantly lower in the reaming debris than from iliac crest samples. In comparing PRP and PPP all detectable growth factors, except IGF-I, were enhanced in the platelet-rich plasma. In the reaming irrigation FGFa (no measurable value in the PRP) and FGFb were higher, but VEGF, PDGF, IGF-I, TGF-beta1 and BMP-2 were lower compared to PRP. BMP-4 was not measurable in any sample. The bony reaming debris is a rich source of growth factors with a content comparable to that from iliac crest. The irrigation fluid from the reaming also contains growth factors.

The initial phase of fracture healing is specifically sensitive to mechanical conditions

Interfragmentary movements affect the quality and quantity of callus formation. The mounting plane of monolateral external fixators may give direction to those movements. Therefore, the aim of this study was to determine the influence of the fixator mounting plane on the process of fracture healing.

Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-β1) from a biodegradable poly(d,l-lactide) coating of osteosynthetic implants accelerates fracture healing in rats

In vitro and in vivo studies have demonstrated an osteoinductive effect of growth factors such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1). However, for therapeutic use in fracture treatment, questions remain with regard to the local application of these proteins. A controlled, local release of growth factors from a biodegradable polylactide coating of osteosynthetic implants may have a stimulating effect on fracture healing. Such implants could stabilize the fracture and their bioactive surface could function simultaneously as a local drug-delivery system. Previous studies have demonstrated the high mechanical stability of an approximately 10-14-microm-thick poly(D,L-lactide) (PDLLA) coating on metallic implants, which can even withstand the process of intramedullary insertion. Following an initial peak, 80% of incorporated growth factors IGF-1 and TGF-beta1 were continuously released within 42 days. The effect of locally applied IGF-1 and TGF-beta1 from a biodegradable PDLLA coating of intramedullary implants on fracture healing was investigated in a rat model. Midshaft fractures of the right tibia of 5-month-old female Sprague-Dawley rats (n = 127) were stabilized with coated vs. uncoated titanium Kirschner wires. X-ray examinations and blood analyses were performed, and body weight and body temperature measurements were taken throughout the experimental period. After 28 and 42 days, respectively, tibiae were dissected for mechanical torsional testing and histomorphometrical analyses. X-rays demonstrated an almost completely consolidated fracture, biomechanical testing showed a significantly higher maximum load and torsional stiffness, and histological and histomorphometric analyses demonstrated progressed remodeling after 28 and 42 days in the group treated with growth factors as compared with controls. Interestingly, the PDLLA coating itself revealed a positive effect on fracture healing even without incorporated growth factors. No systemic changes of serum parameters, including IGF-1 and IGF binding proteins, and no differences in body weight and body temperature were observed within and between groups. These findings suggest that the local application of growth factors from a biodegradable PDLLA coating of osteosynthetic implants accelerates fracture healing significantly without systemic side effects.

Upregulation of TNF-α and IL-3 expression in lesional and uninvolved skin in different types of urticaria

BACKGROUND Although mast cells are known to secrete a broad spectrum of proinflammatory and immunomodulatory cytokines, the role of these molecules in mast cell-dependent cutaneous inflammation is not clear. OBJECTIVE We decided to study biopsy specimens from lesional and nonlesional skin of patients with acute, chronic recurrent, delayed pressure, and cold urticaria; from fleeting wheals of prick test reactions to allergens; and from normal skin of nonallergic subjects. METHODS Cryostat sections were stained by immunohistochemistry with antibodies against IL-3, IL-8, TNF-alpha, and mast cell-specific tryptase. In serial sections with tryptase and each cytokine, reactivity of mast cells was studied as well. RESULTS Compared with normal skin and prick test reactions, immunoreactivity for TNF-alpha and IL-3 was significantly increased on endothelial and perivascular cells of the upper dermis in all urticaria lesions. In nonlesional skin comparable upregulation was noted on endothelial cells and for TNF-alpha on perivascular cells of patients with delayed pressure urticaria. In addition, TNF-alpha was expressed throughout the epidermis in lesional and nonlesional skin of patients with all types of urticaria, but not in normal control subjects. Sequential biopsy specimens from patients with cold urticaria showed upregulation of TNF-alpha and IL-3 on endothelial cells 30 minutes after elicitation of lesions with an ice cube. In contrast to these findings, epidermal immunoreactivity, as well as endothelial and perivascular cell expression of IL-8, were only slightly altered in urticaria compared with normal skin. In sequentially stained sections, few tryptase-positive mast cells reacted to TNF-alpha, few reacted to IL-3 in pressure urticaria only, and practically none stained for IL-8. CONCLUSION These findings suggest that the cytokines studied here are involved in the pathology of urticaria, possibly by inducing subthreshold inflammation in endothelial cells of uninvolved skin.

Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodeling in fracture treatment: A biomechanical and histological study in rats

Bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor (TGF)-beta superfamily, is known to be a very potent osteoinductive growth factor. The purpose of this study was to investigate the effect of BMP-2 (5% [w/w], 50 microg on each nail), locally released from poly(D,L-lactide) (PDLLA)-coated intramedullary implants, on fracture healing. A closed fracture of the right tibia of 5-month-old Sprague-Dawley rats (n = 64) was intramedullary stabilized with uncoated vs. BMP-2-coated titanium Kirschner wires. X-ray examinations (posteroanterior and lateral) were performed throughout the experiment. At 28 and 42 days after fracture, the animals were killed and both tibiae were dissected for biomechanical torsional testing. For histological and histomorphometric evaluation, 5 microm sections were obtained, stained with Safranin-O/light green and von Kossa, and examined using an image analysis system. The radiological results demonstrated progressed callus consolidation in the BMP-2-treated groups compared with the uncoated groups at both timepoints. Histomorphometric evaluation showed progressed callus remodeling with significantly increased mineralization and less cartilage of the periosteal callus. Due to the BMP-2 treatment, increased mineralization of the cortices was detected at 28 and 42 days after fracture. Biomechanical testing revealed significantly elevated maximum load and torsional stiffness in the BMP-2-treated groups compared with controls at both timepoints. The results clearly demonstrate that local application of BMP-2 from PDLLA-coated implants is feasible and significantly accelerates fracture healing. Local administration of growth factors from coated implants could reduce clinical problems in fracture treatment without opening of the fracture, implantation of further devices, or injection with the risk of infection or side effects caused by other carriers.

Where should implants be anchored in the humeral head

To determine histomorphometric and bone strength distribution of the proximal humerus, analyses were done on 24 freshly harvested human cadaveric humeri. Median ages of 46 and 69 years were recorded respectively for the male group (n = 11; minimum, 34 years; maximum, 76 years) and the female group (n = 13; minimum, 46 years; maximum, 90 years). The humeral head was sliced into four equal horizontal levels (Levels 1–4). Five regions of interest were defined in each cutting plane: anterior, posterior, lateral, medial, and central. Histomorphometric analyses evaluated structural parameters (tissue volume to bone volume ratio, trabecular thickness), connectivity (number of nodes, node to node length), and trabecular orientation (mean bone length). The peak values of histomorphometric parameters and bone strength were identified for the cranial section and decreased caudally. The medial and dorsal aspects of the proximal humeral head were found to be the areas of highest bone strength. The trabecular network formed a pattern that connected the center of the gleaned cavity. The structural and connectivity parameters, bone strength, and trabecular orientation showed region- and level-related characteristics. Knowledge of distribution, microstructure, and quality of bone in the humeral head allows the remaining bone stock to be used effectively, even in elderly patients, with a minimally invasive approach and maximum mechanical stability.

Magnetic resonance imaging in the diagnosis of acute injured distal tibiofibular syndesmosis.

RATIONALE AND OBJECTIVES This study assessed the diagnostic potential of magnetic resonance imaging for the evaluation of the tibiofibular syndesmosis. METHODS A total of 38 patients with an acute ankle trauma and clinical suspicion of a syndesmotic tear were prospectively studied with conventional plain film radiography and magnetic resonance imaging. Magnetic resonance imaging studies included plain T1-weighted (T1-w) and T2-weighted (T2-w) sequences and contrast-enhanced T1-w sequences 0 to 3 days after trauma. All images were read by two independent radiologists before surgical intervention. Sensitivity and specificity were determined for the two observers and the concordance of the two observers were calculated using the interobserver analysis (Kappa-Test). Intraoperative inspection (n = 21) revealed rupture of the anterior tibiofibular ligament (ATIF) in 15 patients, intact ATIF in 6 patients, and intact posterior tibiofibular ligament (PTIF) in 21 cases. Clinical and follow-up examinations revealed an intact syndesmotic complex in another 17 patients. RESULTS Primary diagnostic criteria for diagnosing a ligamentous tear included tibiofibular diastasis in conventional plain films; nonvisualization of the ATIF; an abnormal course, a wavy, irregular contour of the ligament; increased signal intensity of the ligament in T2-w sequences, in plain T1-w sequence, and marked enhancement in T1-w after contrast. Important secondary signs were defined as joint fluid in the tibiofibular space and prolapse of interspace fat. Highest diagnostic accuracy was achieved if three or more diagnostic criteria could be visualized. Both readers performed best with the enhanced T1-weighted and the T2-weighted images in transverse orientation. The interobserver analysis resulted in high concordance: Kappa = 0.9 (confidence interval: 0.76 to 1.00) for all patients, and in Kappa = 0.76 (confidence interval: 0.45 to 1.0) for surgically treated patients. CONCLUSIONS Magnetic resonance imaging of the syndesmotic complex is a highly sensitive and specific tool for the pretherapeutic-evaluation of syndesmotic injury.

Isolated traumatic dislocation of the hip. Long-term results in 50 patients

From 1974 to 1989, we treated 50 patients with a simple dislocation of the hip: 38 were posterior dislocations and 12 were anterior. All dislocations primarily treated at our hospital were reduced by closed methods within three hours (mean 85 minutes (10 to 180)) and 43 were reviewed after an average follow-up of 8 years (2 to 17). It is widely held that isolated hip dislocation reduced within six hours gives an excellent outcome, but we found a significant number of complications. There were radiological signs of partial avascular necrosis in two, mild osteoarthritis in seven, and moderate degeneration in two. Heterotopic ossification was seen in four patients, but 29 of 33 MRI examinations were normal. Objective evaluation according to the Thompson and Epstein (1951) criteria showed fair and poor results in 3 of 12 anterior dislocations, but in 16 of 30 posterior dislocations. In six of the seven patients with no other severe injury, the hip had an excellent or good result; in only three of the eight patients with severe multiple injuries was this the case. The important factors in the long-term prognosis appear to be the direction of the dislocation and the overall severity of injuries.