Jan Lassus

Acid attack and cathepsin K in bone resorption around total hip replacement prosthesis.

Normal bone remodeling and pathological bone destruction have been considered to be osteoclast‐driven. Osteoclasts are able to attach to bare bone surface and produce an acidic subcellular space. This leads to acid dissolution of hydroxyapatite, allowing cathepsin K to degrade the organic type I collagen‐rich osteoid matrix under the acidic condition prevailing in Howship lacunae. Using a sting pH electrode, the interface membrane around a loosened total hip replacement prosthesis was found to be acidic. Confocal laser scanning disclosed irregular demineralization of the bone surface in contact with the acidic interface. Cathepsin K, an acidic collagenolytic enzyme, was found in interface tissue macrophages/giant cells and pseudosynovial fluid. Tissue extracts contained high levels of cathepsin K messenger RNA (mRNA) and protein. These observations suggest the presence of an acid‐ and cathepsin K‐driven pathological mechanism of bone resorption, mediated not by osteoclasts in subosteoclastic space, but rather by the uncontrolled activity of macrophages in extracellular space.

Macrophage activation results in bone resorption.

Monocytes or macrophages from important accessory cells in the regulation of bone metabolism and destruction. Cells of the mononuclear phagocyte lineage form the precursor cells of the osteoclasts. Soluble products produced by activated macrophages regulate progenitor cell proliferation, recruitment, differentiation, and activity of osteoblasts and osteoclasts. After osteoclasts are removed from the resorption site, macrophages process bone surfaces and create a cement line before osteoblasts enter to form new bone. Although osteolysis associated with normal bone remodeling is seen as an osteoclast driven process, it may be that in chronic inflammation macrophage activation and vascular derangements lead to low pH, local bone demineralization (acid attack), and H+ mediated stimulation of the primary afferent nociceptive nerve fibers (bone pain). Osteoclasts are not able to attach to demineralized bone or to osteoid surfaces. However, if macrophages degrade the demineralized organic bone matrix, chemotactic factors and attachment sites for osteoclasts are produced. In such a scenario, the osteoclast-osteoblast mediated activation, resorption, and formation cycle would be secondarily activated. Such events may play a role in the most common orthopaedic problem related to macrophage activation, aseptic loosening of orthopaedic joint implants, which is secondary to a chronic foreign body reaction and to micromovement.

Bone stress injuries of the lower extremity: a review.

Bone stress injuries can cause long-lasting damage, especially in young athletes and military conscripts, if not diagnosed and treated properly. Diagnosis has been traditionally based on clinical, radiographic and scintigraphic examinations, but MRI has become increasingly important. High resolution MRI is particularly valuable for the grading of bone stress injuries. The clinician should be aware of the wide range of bone stress injuries and available diagnostic methods. Early diagnosis is the prerequisite for avoiding long-lasting complications. Most bone stress injuries heal with closed treatment, but surgery is necessary in some cases. They heal well if the diagnosis is not delayed and the treatment adequate.

Increased interleukin-8 (IL-8) expression is related to aseptic loosening of total hip replacement.

Abstract Aseptic loosening is an increasing problem in total hip replacement (THR). Chronic inflammatory reaction against implant wear particle results in collageno- and osteolysis, leading to loosening of the implant. Cytokines are known to play a major role in this particular inflammatory process [10]. The aim of the present study was to examine interleukin-8 (IL-8) in the synovial-like interface membrane (SLIM) and pseudocapsular tissue of THRs and to compare it to normal knee synovial membrane. Eleven patients suffering from aseptically loosened THRs were included. All the SLIM and pseudocapsular tissue samples were obtained during revision operations. Ten control samples of normal synovium were collected per arthroscopy from the superior recessus of the knee. For immunohistochemical IL-8 detection, polyclonal mouse anti-human immunoglobulin (Ig)G1 IL-8-primary antibody was used with the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. Results were quantitated using the Vidas image analysis system. The highest count levels (mean ± SEM) were detected in SLIM tissue (386 ± 82 cells/mm2). The difference was statistically significant compared with pseudocapsular tissue (193 ± 36 cells/mm2) and control samples (18 ± 5 cells/mm2). Count levels in control tissue were on average 5% of the SLIM tissues values. The present study determines for the first time the cellular origin of IL-8 in aseptically loosened THRs and also quantitates the IL-8-producing cells in the periprosthetic tissue. The results reveal a high rise in IL-8 concentration in SLIM and in synovial tissues. This finding moves us one step forward in solving the complex network of multiple factors affecting loosening of hip implants.

Production of platelet-derived growth factor in aseptic loosening of total hip replacement.

Abstract Aseptic loosening is the predominant cause of total hip implant failure. It has been assumed that a layer or membrane, containing macrophages, fibroblasts and vascular endothelial cells, of synovial-like tissue develops at the implant-to-bone interface almost invariably and, with time, somehow leads to loosening of the components from the surrounding bone. These cells produce a variety of cytokines and proteolytic enzymes which stimulate bone resorption. Platelet derived growth factor (PDGF) may be one of the cytokines which stimulate bone resorption and contribute to aseptic loosening in total hip replacement (THR). Synovial-like membrane from the implant or cement-to-bone interface (n=10) and pseudocapsule (n=10) were obtained from ten patients operated on for aseptic loosening of THR. As a control, nine samples of connective tissues were obtained from patients who had mandibular or maxillary fractures fixed with bone implant. The avidin-biotin-peroxidase complex (ABC) method with polyclonal rabbit anti-human IgG against the A-chain and B-chain of PDGF was used for staining. ABC-alkaline phosphatase-anti-alkaline-phosphatase double staining with monoclonal mouse anti-human fibroblast IgG1 and CD68 antibodies was used to ascertain the cellular origin of PDGF. Results of the PDGF staining were quantitated by a semi-automatic VIDAS image analysis system. The PDGF-A and PDGF-B chain containing cells were found in all periprosthetic tissues, in particular in macrophages with phagocytosed particulate debris, but to some extent also in fibroblasts and in endothelial cells. The numbers of PDGF-A and PDGF-B chain positive cells per mm2 in synovial-like interface membrane (1881±486 and 1877±214) and pseudocapsule (1786±236 and 1676±152) were higher (P<0.01) around loose THR than in control tissue (821±112 and 467±150), respectively. The results of the present study suggest that PDGF is preferably expressed by macrophages, which to an increased extent produce it in the synovial-like interface membrane and pseudocapsular synovial-like membrane. Because of its role in bone resorption, it may well play a role in periprosthetic bone loss and aseptic loosening and deserves more detailed study as a mediator and potential target in the modulation or prevention of loosening of THR.

No lymphokines in T-cells around loosened hip prostheses.

Research results have been contradictory about the role of lymphocytes and immune response in aseptic loosening of total hip replacement (THR). Conclusive evidence is still lacking in spite of extensive in vivo and in vitro studies. Our study was designed to check whether T-cells were activated and if they produced lymphokines in synovial membrane-like interface tissue around loosened THRs. Tissue sections were stabilized and permeabilized to allow the cytokine-specific antibodies to penetrate through the cell membrane and the membranes of intracellular organelles. This technique, combined with computer-assisted image analysis, permits the detection and quantitation of lymphokine-producing cells. We found that the number of T-cells was low, and none of the T-cells was activated, as shown by the absence of interleukin-2 receptor (IL-2R) immunoreactivity. There was no cell producing lymphokines, such as interleukin-2 (IL-2), interferon-gamma (IFN-^7;), and tumor necrosis factor-beta (TNF-^6;). Our results suggest that T-cell-mediated immune response is not actively involved in aseptic loosening of THR.

Early intramedullary nailing of lower extremity fracture and respiratory function in polytraumatized patients with a chest injury: a retrospective study of 61 patients.

Background The optimal treatment of diaphyseal fractures of the lower extremities in patients who also have serious chest injuries is not known. Patients and methods We retrospectively evaluated the effect of an early intramedullary nailing (IMN) of femur or tibia fractures on respiratory function in 61 consecutive polytraumatized patients with unilateral or bilateral pulmonary contusion (thoracic AIS=3) admitted to our trauma intensive care unit between January 2000 and June 2001. 27 patients had a diaphyseal fracture of at least one long bone of the lower extremity, which was treated with IMN within 24 hours of admission. Results We found no difference between patients with or without a lower extremity fracture regarding the length of ventilator treatment, oxygenation ratio (PaO2/FiO2) or in the incidence of acute respiratory distress syndrome (ARDS), pneumonia, multi-organ failure or mortality. Interpretation In this retrospective study, IMN of a long bone fracture in a patient with multiple injuries and with a coexisting pulmonary contusion did not impair pulmonary function or outcome.

Hyaluronan synthases, hyaluronan, and its CD44 receptor in tissue around loosened total hip prostheses.

Aseptic loosening of prosthetic components, the most common long‐term complication after total hip replacement (THR), is characterized by the formation of a synovial membrane‐like interface tissue (SMLIT). It was hypothesized that the hyaluronan synthase (HAS)/hyaluronan (HA)/HA receptor CD44 signalling system is responsible for the synovial‐like differentiation of the interface membrane. SMLIT was therefore compared with osteoarthritis (OA) synovial membrane by using reverse transcriptase polymerase chain reaction (RT‐PCR) of HAS 1, 2 and 3, histochemical HA assay, and immunohistochemistry of CD44 and its non‐HA ligands. All three isoforms of HAS were found in these samples. HA and CD44 were most abundant in the lining, but the signal was actually stronger in aseptic loosening than in OA (p<0.01). The non‐HA CD44 ligands, collagen type VI, fibronectin, osteopontin, and MCP‐1, had a similar distribution pattern in both tissues. These results confirm the synovial‐like structure of the interface tissue lining. The pressure waves and movement of the HA‐rich pseudosynovial fluid seem to drive HA into the implant‐to‐host interface, which itself also produces HA. HA may be responsible for the induction of a synovial‐like lining at the interface through HA‐CD44 signalling. Copyright

Carbon dioxide (CO2)-laser therapy cures macroscopic lesions, but viral genome is not eradicated in men with therapy-resistant HPV infection

Background and Objectives We have evaluated the efficacy of CO2-laser in eradicating human papillomavirus (HPV) DNA from genitoanal skin lesions. Study Design Biopsies of 38 male patients with histologically confirmed HPV-infection after an average of 2 years of follow-up were analyzed. Post-treatment biopsies were obtained from all residual or recurrent HPV-suspect (acetowhite) lesions in 23 patients. Results After an average of three separate CO2-laser treatments, 15 of 38 patients were devoid of any clinical or acetowhite lesions. By in situ hybridization (ISH), the frequency of HPV types 6/11 decreased from 52% to 26%, and HPV-types 16/18 decreased from 48% to 17%, respectively, in 23 patients biopsied twice. When ISH-negative biopsies were further analyzed with polymerase chain reaction (PCR) and southern blotting (SB) for HPV-16, HPV-types 16/18 were detected in a total of 65% of biopsies before CO2-laser therapy, and in 61% after the therapy. The cure rate achieved with CO2-laser was 39% (15/38) according to clinical, 61% (14/23) according to histopathological, and 26% (6/23) according to molecular biological criteria. The frequency of Bowenoid papulosis was reduced from 57% (13/23) to 17% (4/23). Conclusions Although CO2-laser is ineffective in eradicating HPV genome from therapy-resistant penile warts, the treatment reduces the recurrence of atypical changes and visible warts.

Myocardial contusion as a cause of delayed cardiac rupture. A case report

a Department of Orthopaedics and Traumatology, Helsinki Uni ersity Central Hospital, Topeliuksenkatu 5, FIN-00260 Helsinki, Finland b Department of Anatomy, Institute of Biomedicine, Uni ersity of Helsinki, Helsinki Finland c Department of Oral Medicine, Surgical Hospital, Helsinki Uni ersity Central Hospital, Helsinki, Finland d Department of Oral Medicine, Institute of Dentistry, Uni ersity of Helsinki, Helsinki, Finland