The biomolecular interactions between endothelium and bone cells: an overview.

Bone turnover is a complex set of different molecules pathways and it is strictly connected with bone vasculature. It includes every bone process concerning bone modelling and remodelling such us skeletal growth and healing process. A fundamental component of this bone architecture is played by the endothelium, that acts in a paracrine fashion on other bone stromal cells via humoral factors, growth factors and chemokines/cytokines. The alteration of those biochemical interactions between endothelium, vasculature and bone tissue may cause various pathological manifestations. Understanding the bases of the interaction between those different pathways could provide novel therapeutic strate¬gies for bone disease. The Authors present an updated overview of the most common communication biomolecules between bone cells and endothelium and their interactions both in healthy and pathological conditions. Furthermore, focusing on gene and related therapies, possible future therapeutic strategies for bone vasculature/metabolic diseases are presented.

Reconstructive techniques for revision and limb salvage surgery in persons with haemophilia.

Haemophilia is an inherited haemorrhagic disease characterized by the lack of coagulative factors associated nowadays mostly to musculoskeletal complications, particularly severe secondary arthritis in specific joints. Recurrent traumatic or spontaneous joint bleeding, induce severe arthropathy at a young age that can be treated only by joint replacement. Total knee or hip arthroplasty in young subjects may fail earlier due to wear or infections and in the haemophilic population, this means bone loss, pseudo tumours and the need of revision or even limb salvage surgery. Modern modular implants and the use of bone graft enriched by tissue engineering techniques such as a concentration of autologous mesenchymal cells or PRP may be helpful to compensate all bone loss and anatomic alterations due to failures of orthopaedic implants. The authors present their experience with this type of surgery and their biological approach to these challenging cases.

Agonistic anti-human Fas monoclonal antibody induces fibroblast-like synoviocyte apoptosis in haemophilic arthropathy: potential therapeutic implications.

Haemophilic arthropathy (HA) is characterized by chronic proliferative synovitis leading to cartilage destruction and shares some pathological features with rheumatoid arthritis (RA). Apoptosis has been implicated in RA pathogenesis, and an agonistic anti-Fas monoclonal antibody (mAb) was found to induce RA fibroblast-like synoviocyte (FLS) apoptosis and suppress synovial hyperplasia in animal models of RA. The aim of this study was to evaluate the effect of anti-Fas mAb on HA-FLS. FLS were isolated from knee synovial biopsies from six HA patients, six RA patients and six healthy subjects. The expression of Fas in synovial biopsies was investigated by immunohistochemistry. FLS were stimulated with anti-Fas mAb at different concentrations, alone or in combination with tumour necrosis factor-α (TNF-α) and basic fibroblast growth factor (bFGF). Fas expression in FLS was assessed by Western blot. Cell viability was studied with the WST-1 assay. Active caspase-3 levels were measured using ELISA and Western blot. A strong Fas-immunoreactivity was observed in different cells of HA synovium, including FLS, inflammatory cells and endothelial cells. Fas antigen was constitutively overexpressed in cultured HA-FLS. Anti-Fas mAb had a significant cytotoxicity on HA-FLS in a dose-dependent manner, either alone or in combination with TNF-α and bFGF. These cytotoxic effects were due to the ability of anti-Fas to induce HA-FLS apoptosis, as shown by the increased active caspase-3 levels. Anti-Fas mAb exhibited a more pronounced pro-apoptotic effect on HA-FLS than RA-FLS. Fas antigen is highly expressed on HA-FLS and its stimulation by anti-Fas mAb may be an effective strategy to induce HA-FLS apoptosis.

Viscosupplementation in haemophilic arthropathy: a long-term follow-up study.

Haemophilic arthropathy is the most common clinical manifestation of haemophilia, secondary to recurrent haemarthroses and chronic synovitis. Modern bleeding-preventing drugs have limited significantly the incidence of severe arthropathy, and primary approach is usually conservative. Use of intra-articular injections of hyaluronan acid is considered one of the most efficient treatments for early stages of articular degenerative diseases. Assessment of long-term effectiveness of intra-articular administration of hyaluronic acid (HA) in knees, ankles and elbows of patients affected by haemophilic arthropathy was done for 46 patients (10 elbows, 24 knees and 25 ankles) affected by haemophilic arthropathy. They received injections of HA and were evaluated with Visual Analogue Scale, Short Form-36, World Federation of Haemophilia score and Petterson score with a 6-year mean follow-up. Most of the patients showed improvement in pain relief and functional recovery without any complications: only a limited number of patients (8.6%) found poor results, undergoing surgery or other further treatments in the follow-up period for persistent pain or limitation. Viscosupplementation is an effective therapeutic strategy in early stages of haemophilic arthropathy, with no complications and long-term good clinical results.

A rare association of inlet patch with laryngospasm: a report of two children and literature review.

The inlet patch (IP) is an area of heterotopic gastric mucosa in the cervical esophagus commonly seen during upper endoscopy. Although generally asymptomatic IP has been associated with esophageal and supraesophageal symptoms and, though rare, in adult with malignant transformation. We describe two cases of recurrent episodes of laryngospasm associated with IP. In both cases there was a good response to prolonged acid suppression therapy.

Acetabular revisions using a cementless oblong cup: five to ten year results.

The purpose of this paper was to evaluate the results of acetabular revisions with the use of an oblong revision cup that is designed with its longitudinal diameter elongated relative to its transverse diameter. Between 1996 and 2001, 62 hips in 60 patients underwent an acetabular revision with the insertion of a LOR acetabular component. Seven hips were lost to follow-up or the patients died; the remaining 55 hips (53 patients) remained in follow-up for an average of 7.2 years (range: 5.0-10.1 years). One socket was revised for aseptic loosening, and another was operated on for a late polyethylene liner dissociation. The average Harris hip score (HHS) improved from 34 to 79. Results were rated as excellent in 16 hips, good in 28, fair in six and poor in three. Radiographic analysis demonstrated an improvement in the average vertical displacement of the hip centre: 49 hips had a well-fixed, bone-ingrown cup and four had a stable fibrous union. For large superolateral acetabular bone deficiencies, this implant facilitated a complex reconstruction without the need for bulk structural acetabular bone grafts, provided good clinical results and showed satisfactory stability at the midterm follow-up.

A modular total knee arthroplasty in haemophilic arthropathy.

The results of 24 modular Genesis II (Smith & Nephew, Memphis, TN, USA) total knee arthroplasties, performed in 20 patients with haemophilia were prospectively reviewed. The hypothesis that the use of a new-generation implant and advanced, more aggressive hematological care, will result in a decrease rate of complications and better functional results for the haemophilic patients with TKA was tested. The mean age at the time of surgery was 36 years (25 to 44). All the patients were reviewed clinically and radiologically with an average follow-up of 4.4 years (2 to 7 years). At the final follow-up the knee score improved from an average of 23 points (11 to 45) to 86 points (62 to 100; p<0.001). The mean knee flexion contracture improved from 22 degrees (0 degrees to 45 degrees ) to 3 degrees (0 degrees to 10 degrees ; p<0.0001). The mean total flexion arc improved from 69 degrees (5 degrees to 130 degrees ) to 92 degrees (80 degrees to 145 degrees p<0.001). The results of our study confirm that the introduction of modular design may improve the functional results of TKA in haemophilic arthropathy which results in a better range of motion and lower flexion contracture.

Planning for minimally invasive unicompartmental knee arthroplasty.

Unicompartmental knee arthroplasty (UKA) is considered the treatment of choice in patients with single compartment arthritis of the knee at early stages or with osteonecrosis limited to one compartment. However, results in the literature are still controversial and it is a technically difficult procedure. The main goal of UKA is to restore the articular space of the afflicted compartment, without influencing the limb alignment. Selection of patients and pre-operative planning are crucial. The necessity to improve functional results and to reduce immobilization of the patients has led to the development of minimally invasive surgery. Applied to UKA, this approach reduces blood loss and surgical time, causes fewer symptomatic postoperative complications, and permits earlier recovery compared to the traditional incision. The shorter incision makes careful pre-operative planning essential. We briefly review the indications for UKA, the pre-operative clinical and radiological assessment, and the surgical procedure.