Positive effect of oral supplementation with glycosaminoglycans and antioxidants on the regeneration of osteochondral defects in the knee joint.

The effect of oral supplementation with glycosaminoglycans (GAG) and radical scavengers (vitamin E/selenium) on the regeneration of osteochondral defects was investigated in rabbits. After introduction of defined osteochondral defects in the knee joint, groups of ten animals were given a GAG/vitamin E/selenium mixture or a placebo (milk sugar) for 6 weeks. Following sacrifice, histological and histochemical analysis was performed. The amount of synovial fluid was increased in the placebo group, while the viscosity of the synovial fluid was significantly enhanced in the GAG group. The amount of sulfated GAG in the osteochondral regenerates (8.8 +/- 3.6 % vs. 6.0 +/- 5.6 %; p <0.03) was significantly higher in the GAG group. In both groups, the GAG amount in the cartilage of the operated knee was significantly higher than in the non-involved knee (p <0.05). Histological analysis of the regenerates in the GAG group was superior in comparison with the placebo group. For the first time, a biological effect following oral supplementation with GAG was demonstrated in healing of osteochondral defects in vivo. These findings support the known positive clinical results.

Second generation of meniscus transplantation: in-vivo study with tissue engineered meniscus replacement.

INTRODUCTION: The options available after meniscus loss offer only limited chances for a long-term success. In the following experimental study, we investigated the effect of meniscus tissue engineering on properties of the collagen meniscus implant (CMI). METHODS: Autologous fibrochondrocytes, obtained per biopsy from adult Merino sheep (n=25), were released from the matrix, cultured in-vitro and seeded into CMI scaffolds (n=10, group 1). Following a 3-week in-vitro culture, the tissue engineered menisci were used for autologous transplantation. Macroscopical and histological evaluation were performed in comparison with non-seeded CMI controls (n=10, group 2) and with meniscus-resected controls (n=5, group 3) after 3 weeks (each 1 animal group 1 and 2) and 3 months. RESULTS: The lameness score did not show any difference between the groups. Meniscus tissue was found in seven knee joints (group 1), in five knee joints (group 2) and in two knee joints (group 3). The size of the transplants reduced from 25.9+/-4.5 to 20.1+/-10.8 mm (group 1) and from 25.9+/-1.5 to 14.4+/-12.5 mm (group 2). Histologically, enhanced vascularisation, accelerated scaffold re-modelling, higher content of extra-cellular matrix and lower cell number were noted in the pre-seeded menisci in comparison with non-seeded controls. Dense high-cellular fibrous scar tissue was found in two of five cases in the resection control group. CONCLUSION: Tissue engineering of meniscus with autologous fibrochondrocytes demonstrates a macroscopic and histological improvement of the transplants. However, further development of the methods, especially of the scaffold and of the cell-seeding procedure must prove the feasibility of this procedure for human applications.

[Efficiency of a postoperative treatment after rotator cuff repair with a continuous passive motion device (CPM)]. / Effektivität der postoperativen Behandlung mittels motorisierter Bewegungsschienen (CPM) bei Patienten mit Ruptur der Rotatorenmanschette.

AIM: The main objective of this study was to prove that a postoperative combined continuous passive motion (CPM) and physiotherapy treatment protocol (CPM group) can achieve 90 degrees active abduction in the shoulder joint earlier than physiotherapy alone (PT group). The indication was a complete tear of the rotator cuff. METHOD: The study was conducted under in-patient and out-patient conditions. 55 patients were included in this study. The prospective, randomized multicenter study design complies with DIN EN 540. The primary endpoint was the time span until 90 degrees active abduction was achieved by the patients. RESULTS: Patients in the CPM group reached the primary endpoint on average 12 days earlier than the control group. This difference was statistically significant (p = 0.0292). Analyzing the secondary endpoints, e. g., pain and disablement, the results in the CPM group showed again advantages of the combined treatment protocol (CPM + physiotherapy). CONCLUSION: The postoperative treatment of a total tear of the rotator cuff with a combined continuous passive motion and physiotherapy protocol provided a significantly earlier range of motion in the shoulder joint than physiotherapy alone. There was no report of CPM-related adverse effects.

[Analysis and adjustment of acid-base disturbances according to the Stewart-Fencl principle]. / Analýza a korekce poruch acidobazické rovnováhy na základe Stewartova-Fenclova principu.

In 1983, P. J. Stewart proposed a new approach for evaluation of acid-base balance of body fluids. He defined three independent variables responsible for hydrogen ion concentration in body fluids: 1. the partial pressure of carbon dioxide (pCO2); 2. strong ion difference, SID, i.e. the difference between the sums of all the strong (fully dissociated, chemically nonreacting) cations and sums of the strong anions; 3. the total concentration of all the non-volatile weak acids (mainly albumin) designated as [Atot]. On the basis of this theory, V. Fencl invented a new classification of clinical acid-base disturbances. Respiratory acidosis and alkalosis result from abnormalities of pCO2. The classifications of the respiratory disturbances of ABR is identical as in the conventional viewing which is based on the dissociation equation of carbonic acid. Metabolic acidoses or alkaloses result from derangements of the SID and/or [Atot]. The change of SID value is a consequence of either dehydration (alkalosis) or hyperhydration (acidosis). Other mechanisms of SID deviation are either changes of serum chloride concentration (an increase causes acidosis, a decrease causes alkalosis) or an increase of concentrations of substances not routinely measured (ketones, lactate, exogenous acids). [Atot] value is determined mainly by the serum albumin concentration (alkalosis in hypoalbuminemia, acidosis in hyperproteinemia). The Stewart-Fencl approach to acid-base balance enables to understand and predict what happens to hydrogen ions in body fluids and to control the pH abnormalities quantitatively.

Inducible nonviral gene expression in the treatment of osteochondral defects.

OBJECTIVE: The repair of osteochondral defects with chondrocytes genetically modified to express desired growth factors promises great potential in orthopaedic therapy. Controlled expression of the transgenes is required in many instances. The objective of the present study was to demonstrate the inducibility of tetracycline-responsive transgene expression in osteochondral defects in the knee joint filled with genetically modified chondrocyte implants. METHODS: An expression plasmid containing the lacZ gene under the control of the minimal CMV promoter fused to the Tet-responsible element (TRE) as well as the reverse transactivator (rtTA2s-M2) was constructed and used to transfect isolated articular chondrocytes from New Zealand white rabbits. rtTA2s-M2 binds to the TRE in the presence of tetracycline and leads to the transcription of the transgene. Different concentrations of DNA and various DNA:lipid ratios were tested to determine best transfection conditions. Transfection efficiency and inducibility were analysed by histochemical analysis and flow-cytometry. To evaluate the system in vivo, collagen-sponges were seeded with transfected autologous chondrocytes and implanted in osteochondral defects in the knees of NZW-rabbits. Gene expression was induced by doxycycline and 3 weeks later, LacZ-expression in isolated knee joints was evaluated in histological sections by X-gal staining. RESULTS: In vitro 13.5% (+/-1.32) of induced primary chondrocytes were LacZ-positive, while non-induced controls showed a background-staining in 0.6% (+/-0.2). In vivo, upon doxycycline treatment, induction of lacZ-gene-expression could be demonstrated in chondrocytes in 3-week-old, well-integrated implants. CONCLUSION: For the first time, tetracycline-inducible gene expression is demonstrated to work in the treatment of osteochondral defects. This demonstrates the feasibility for a gene therapy-assisted approach using controlled expression of therapeutic growth factors from transplanted genetically modified chondrocytes.

[IgA nephropathy. Use of modern laboratory methods and renal biopsy for diagnosis]. / IgA nefropatie. Uzití moderních laboratorních metod a biopsie ledviny v diagnostice.

IgA nephropathy is the most frequent primary glomerulonephritis worldwide. At its onset, the most common laboratory sign is isolated haematuria often accompanied with mild proteinuria (up to 1.5 g/24 h). The disease displays a progressive course with end-stage renal disease occurring in up to half of patients 20 years after onset. Diagnosis is established by immunofluorescent microscopy of a renal biopsy specimen. Discoveries in the past decade on the pathogenesis of IgA nephropathy together with complex evaluation of its clinical presentation enable to establish diagnosis with a satisfactory degree of probability even without biopsy. IgA nephropathy patients display increased or borderline serum IgA levels; increased serum levels of IgA fraction with degalactosylated O-linked side sugar chains; increased serum levels of anti-N-acetylgalactosamine antibodies; increased levels of circulating immune complexes composed of IgA1 complexed with IgG or IgA1; increased serum levels of circulating complexes composed of IgA and fibronectin; and frequent occurrence of the rheumatoid IgA factor. Clinical use of these still generally unavailable methods would reduce the renal biopsy indication in patients with isolated or predominant haematuria.

[Development of a 3-dimensional method to determine the tibial slope with multislice-CT]. / Entwicklung eines 3-dimensionalen Messverfahrens zur Bestimmung des tibialen Gefälles im Spiral-CT.

AIM: The measurement or, respectively, the correction of the tibial slope is an important subject in the field of knee arthroplasty and in the procedure of cruciate ligament reconstruction. However, a valid value of the tibial slope cannot be obtained from the conventional plain X-rays in a reproducible way. The aim of this study was to evaluate the proximal tibial slope with a new CT measurement system and to compare the values with the X-ray method. METHOD: Using 6 cadaver tibiae, the antero-posterior slope of the proximal tibia was measured at 0 degrees, 2.5 degrees, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 30 degrees internal rotation using the plain X-ray and spiral CT (3D-MPR reconstruction). Both methods were compared. RESULTS: The variation of the measurement of the tibial slope with the X-ray method was > 5 degrees even if the optimal 0 degrees rotation in the lateral view was applied. Moreover, the measurement error increased to 14 degrees while increasing the rotation of the tibia. Using the new CT system, the error was less than 3 degrees in all measurements. CONCLUSION: The measurement of the tibial slope in the conventional X-ray technique showed a high variation of the values depending on the rotation of the tibia in the lateral view. In contrast, the measurements with the new CT system represented a precise method with a small variation of the tibial slope values. For this reason detailed questions regarding the precise anatomy of the proximal tibia cannot be answered precisely with plain X-rays.

[Revision of failed anterior cruciate ligament reconstruction]. / Revision nach fehlgeschlagener VKB-Plastik.

Failures of ACL reconstruction still occur despite improved arthroscopic methods and new technical instruments. The reasons for failures, which are mostly related to technical surgical errors, must be recognized, analyzed, and considered for the planning and execution of revision ACL surgery. This review article describes the reasons for failed ACL reconstructions, indications, preoperative evaluation, planning, and performance of the operative procedure as well as the issue of rehabilitation. The strategies are evaluated for graft selection, staging of the revision, and the steps of the operative procedure including hardware removal, tunnel placement, graft fixation, or additional operations. Special attention is given to the dilemma of arthrofibrosis and its management in ACL revision cases. Since the results are worse after revision than following primary ACL surgery, the operative procedure has to be tailored to the needs of the patient, planned carefully, and performed by an experienced knee surgeon.

Treatment of osteochondral injuries. Genetic engineering.

Articular cartilage injuries are commonly encountered problems in sports medicine and orthopaedics. The treatment of chondral and osteochondral lesions, which possess only a very limited potential for healing, still represents a great challenge to clinicians and to scientists. Experimental investigations reported over the last 20 years have shown that a variety of methods, including implantation of periosteum, perichondrium, artificial matrices, growth factors, and transplanted cells, can stimulate formation of new cartilage. Genetic engineering--a combination of gene transfer techniques and tissue engineering--will facilitate new approaches to the treatment of articular cartilage injuries.

The fate of the poly-L-lactic acid interference screw after anterior cruciate ligament reconstruction.

We report the persistence of a poly-L-lactic acid (PLLA) interference screw 2.5 years after anterior cruciate ligament (ACL) reconstruction with Achilles tendon allograft. The arthroscopy was performed because the patient sustained a reinjury of the ACL graft, making ACL revision surgery necessary. At the time of arthroscopy, both PLLA screws were macroscopically still intact but could not be removed in 1 piece. No inflammation could be observed either macroscopically or in the histologic analysis. The biopsy specimen from the femoral insertion of the graft showed parts of the PLLA material surrounded by scar tissue. This case shows that biodegradation of PLLA material in the knee joint causes no irritation and can take several years, even if the material is in contact with the synovial fluid.

Accuracy in tunnel placement for ACL reconstruction. Comparison of traditional arthroscopic and computer-assisted navigation techniques.

The purpose of this randomized, prospective study was to compare accuracy in tunnel placement as performed with a traditional arthroscopic anterior cruciate ligament (ACL) reconstruction technique and with KneeNavTM ACL, a computer-assisted surgical navigation technique. Two surgeons experienced in ACL reconstruction, but inexperienced in computer-assisted surgical navigation technique, each randomly used traditional arthroscopic guides or KneeNavTM ACL to drill a tunnel in twenty identical foam knees. Placement of the resulting tibial and femoral tunnels was measured with a computer-assisted digitizing method and compared to traditional biplanar radiographs. Statistical analysis with Student's t-test was used to compare the distance from the ideal tunnel placement to the femoral and tibial tunnels. Accuracy of tunnel placement with KneeNavTM ACL was significantly better than that obtained with the traditional arthroscopic technique. Distances from the ideal tunnel placement to the femoral and tibial tunnels were 4.2 +/- 1.8 mm (mean +/- SD) and 4.9 +/- 2.3 mm, respectively, for the traditional arthroscopic technique, and 2.7 +/- 1.9 mm (femur) and 3.4 +/- 2.3 mm (tibia) for KneeNavTM ACL. These differences were statistically different. Tunnel placement for ACL reconstruction with KneeNavTM ACL, an image-based, computer-assisted surgical navigation device with a simple and intuitive interface, was more accurate than with the traditional arthroscopic technique.

Long-term follow-up of patients presenting to adult nephrologists with chronic pyelonephritis and 'normal' renal function.

We studied the natural history, and therefore prognosis, of patients with chronic pyelonephritis presenting to adult nephrologists with a plasma or serum creatinine <90 mmol/l. From the Newcastle chronic pyelonephritis database, 255 patients with radiologically-proven disease were reviewed. Median follow-up was 95 months (95%CI 82. 3-109.3). Plasma creatinine was < or =90 micromol/l (P(Cr)< or =90 group) at presentation in 138. At presentation, hypertension, bilateral disease and proteinuria were less frequent in the P(Cr)< or =90 group (hypertension 19% vs. 32%, p<0.05; bilateral disease 25% vs. 70%, p<0.001; proteinuria 18% vs. 60%, p<0.001). With the exception of two patients, the renal prognosis of this group was excellent. Patients over the age of 18 years presenting to adult nephrologists with a diagnosis of chronic pyelonephritis and a creatinine < or =90 micromol/l can be reassured that the chances of developing end-stage renal failure in the future are very small. Most could be referred back to their general practitioner for long-term follow-up.

[Tissue engineering and gene therapy of the musculoskeletal system with muscle cells]. / Tissue Engineering und Gentherapie des Bewegungsapparates mit Muskelzellen.

AIM: Muscle-based somatic gene therapy is a novel way to alleviate a biochemical deficiency. METHOD: Muscle-derived cells are very promising in the field of gene therapy and tissue engineering. First, most muscle tissue is accessible by injection. Second, muscle tissue consists of multinucleated, postmitotic myofibers, which enable a long-term expression of the transduced gene. Third, muscle tissue can be biopsied easily. It is available in abundance and the biopsy does not compromise the health and function of the patient. Finally, muscle tissue is highly vascularized, which makes systemic delivery feasible. RESULTS: Muscle-derived cells can promote muscle healing and bone healing. Implanted cells maintain a long-term transgene expression of therapeutic proteins. Isolated, muscle-derived stem cells can differentiate in osteoblasts. CONCLUSION: Based on these characteristics, we present four possible applications: inherited muscular diseases, muscle injury, bone healing, and intraarticular disorders.

[Postural trauma and rhabdomyolosis causing acute renal failure]. / Pozicní trauma s rabdomyolýzou a následným akutním renálním selháním.

Rhabdomyolysis (damage of the muscles of various origin) leads to the efflux of the intracellular fluids in the circulation. The common complication of this status is the renal failure. The early diagnosis and the proper treatment makes the fall of renal function reversible. That is why the possibility of the rhabdomyolysis must be consider. The case report describes the development of renal failure in young, previously healthy men, followed by trauma mechanism after drug and alcohol abuse.

Gene therapy and tissue engineering in sports medicine.

Treatment of sports injuries has improved through sophisticated rehabilitation programs, novel operative techniques, and advances in biomechanical research during the past two decades. Despite considerable progress, treatments remain limited due to poor healing capacity for anterior or posterior cruciate ligament rupture, central meniscal tear, cartilage lesions, and delayed bone fracture. New biological approaches seek to treat these injuries with growth factors to stimulate and hasten the healing process. Gene therapy using the transfer of defined genes such as those encoding growth factors represents a promising way to deliver therapeutic proteins to the injured tissue. Tissue engineering, which may eventually be combined with gene therapy, offers the potential to create tissues or scaffolds for regeneration of defects occurring from trauma.

Operative treatment of combined anterior and posterior cruciate ligament injuries in complex knee trauma: can the cruciate ligaments be preserved?

A retrospective study was performed focusing on operative treatment after combined anterior cruciate ligament (ACL)/posterior cruciate ligament (PCL) injuries. The operative treatment included the preservation of one or both cruciate ligaments. Twenty-eight patients, average age 30 years (range: 12-55 years), were evaluated 5.4 years (range: 1-14 years) postoperatively. Twenty-two operations were performed in patients with acute injuries (<30 days after trauma) and 6 operations in patients with chronic instabilities (>30 days after trauma). Both cruciate ligaments were preserved by suture or refixation in 16 patients. Suture of one and reconstruction of the other cruciate ligament with autologous tendon graft was performed in 12 cases. In addition, 61 procedures (meniscal suture/resection, medial/lateral reconstruction, tendon suture, and open reduction and internal fixation were performed. Postoperative treatment included continuous passive motion and protected weight bearing. Eleven (27% acute, 83% chronic) patients required revision (ACL/PCL reconstruction, osteotomy, and meniscal repair). At follow-up, 43% of the patients were very satisfied and 46% were satisfied. Seventy-one percent (89% preinjury) of the patients were able to maintain intensive and moderate International Knee Documentation Committee (IKDC) activity levels. The IKDC evaluation of the patients (acute %/chronic cases %) was graded for symptoms: A 39% (45/17), B 35% (27/67), C 15% (18/0), and D 11% (9/17); for range of motion: A 42% (36/67), B 42% (50/17), C 16% (14/17), and D 0%; and for ligaments: A 21% (18/17), B 33% (45/0), C 42% (32/83), and D 4% (5/0). Radiographic findings were A 18%, B 41%, and C 41%. Primary repair of acute injuries was superior to the delayed repair of chronic instabilities. Preservation of cruciate ligaments in acute combined ACL/PCL tears results in a satisfying knee function despite distinct residual ligament instability. Although suture of the cruciate ligaments in open technique is a therapeutic option in acute multiligamentous knee injuries, it is not recommended for the treatment of chronic instabilities.

[To brace or not to brace? How effective are knee braces in rehabilitation?]. / To brace or not to brace? Wie sinnvoll sind Knieorthesen in der Rehabilitation?

Since the clinical benefit of knee braces has yet to be defined, discussion about braces after reconstructive surgery of the anterior cruciate ligament remains controversial. The use of prophylactic braces in sport did not prove to be effective. In ACL insufficient knee joints, the operative treatment is preferred over the use of functional knee braces. Therefore, the postoperative rehabilitation presents the main application of braces. Modern operative techniques with an initial strong fixation of the ACL graft make a functional postoperative treatment without external fixation possible. In the presented meta-analysis of the literature about knee braces, results from clinical and experimental studies are compared. No published clinical data have shown that braces have any effect on postoperative outcome after ACL-reconstruction. Also, no evidence of a significant bracing effect could be demonstrated in the experimental in vivo or in vitro studies, except a limited stabilizing function for lower shear stress below the physiological loads. Consequently, the systematic use of braces in the rehabilitation after ACL reconstruction cannot be recommended.