T-cell precursor frequencies and long-term outcome following unrelated hematopoietic stem cell transplantation.

Functional assays measuring alloreactivity of donor cells are desired to detect either cryptic epitopes inducing graft-vs.-host disease (GvHD) after human leukocyte antigen (HLA)-identical hematopoietic stem cell transplantation (HSCT) or permissible HLA mismatches. However, their value in predicting GvHD and survival is still limited. We determined the cytotoxic and helper T-cell precursor (CTLp and HTLp) frequencies by limiting dilution analysis (LDA) in 40 unrelated recipient/donor combinations. The median observation period at the time of this writing was 4.44 years (range from 0.1 to 11.28). Better overall survival was observed in patients with rather low host-specific CTLp and HTLp frequencies, whereas a trend toward high CTLp frequencies was seen in patients with higher incidence of acute GvHD, especially in patients mismatched in HLA-C. CTLp and HTLp frequencies did not correlate with the incidence of chronic GvHD and relapse. In conclusion, we detected a trend toward better overall survival of patient/donor pairs with low CTLp and HTLp frequencies, however, recommend to use LDA as an additional tool for identifying the most suitable donor when more than one fully HLA-matched stem cell donor is available.

Comparison of total and partial traumatic tears of the subscapularis tendon.

We treated surgically 16 shoulders with an isolated traumatic rupture of the subscapularis tendon over a six-year period. Nine patients had a total and seven a partial tear of the subscapularis tendon. Repair was undertaken through a small deltopectoral groove approach. The mean Constant score improved in total tears from 38.7 to 89.3 points (p = 0.003) and in partial tears from 50.7 to 87.9 points (p = 0.008). The total tears were significantly more improved by surgery than the partial tears (p = 0.001). The delay between trauma and surgery was inversely proportional to the improvement in the Constant score suggesting that early diagnosis and surgical repair improves outcome.

[Limitation of shoulder mobility due to ankylosis of the sternoclavicular joint in SAPHO syndrome]. / Das SAPHO-Syndrom als Ursache von Bewegungseinschränkungen der Schulter.

The rare case of limited range of motion of the shoulder due to ankylosis of the sternoclavicular joint in SAPHO syndrome is presented. The symptoms and the resection arthroplasty of the sternoclavicular joint are discussed.

[Treatment of trochanteric fractures with the gamma nail]. / Die Versorgung trochanterer Frakturen mit dem Gammanagel.

The osteosynthesis of trochanteric fractures requires a minimal invasive technique to guarantee fully weight bearing and early rehabilitation in elderly patients. In this retrospective study we want to prove if the gamma nail meets all requirements and if the results improved after initiation of the new instrumentarium and standardization of the operative technique. From January 1992 until April 2000 we treated 387 patients with a gamma nail. The average age was 79.4 years. We used the new instrumentarium suitable for radiography since June 1996, the operative technique was standardized since the same time. The evaluation occurred on the basis of clinical and radiological findings included analysis of complications. We've seen intraoperative problems in 29% before June 1996, this rate could be reduced to 9%. General postoperative complications presented in equal frequency. After improvement of the technique dislocations of the neck screw and relevant sinking of the fractures were more rarely. The rate of reoperations after complications of the implant was 8% in both groups. In consideration of technical standards the postoperative full weight bearing and early mobilisation is possible even in old patients.

[Diagnosis and stage-related therapy of joint infections]. / Diagnostik und stadiengerechte Therapie von Gelenkinfekten.

BACKGROUND: Our management of septic arthritis is a combination of a stage-related arthroscopic irrigation, debridement and antibiotic therapy. At the start of therapy x-rays of the infected joint, leukocyte rate with differentiation and C-reactive protein level are necessary and aspiration of the joint should be performed for gram strain and crystal analysis. Additional imaging and laboratory tests can be needed for special indications. An arthroscopic staging of the initial joint infection has been shown to have prognostic and therapeutic consequences. Antibiotic therapy should start after aspirates and biopsy specimen have been taken intraoperatively and has to be adapted to the final results of the microbiology. Overall, antibiotic therapy is necessary for a period of 4-6 weeks, unless clinical findings and laboratory tests have returned to normal. A transition to oral administration of antibiotics is possible prior to patient release. INTRAOPERATIVE TREATMENT: Intraoperatively, the synovial membrane should be left intact. There is no indication for the intra-articular use of antibiotics and antiseptics. Wound drains are not necessary. If symptoms of infection persist under antibiotic therapy, arthroscopic irrigation can be repeated with good results.

Arthroscopic management of septic arthritis: stages of infection and results.

Seventy-six patients with septic arthritis (78 affected joints) were treated with a combination of arthroscopic irrigation, debridement, and antibiotic therapy according to the tested bacterial sensitivity. There were 62 knee, 10 shoulder, 5 ankle joints, and 1 hip joint. No antibiotics were added to the irrigating solution. The arthroscopic and radiological stage of infection, treatment, and outcome in these patients was analyzed. The patients were classified into three groups according to initial stage of joint infection (stage I: 21 patients, 22 joints; stage II: 43 patients, 44 joints; stage III: 12 patients, 12 joints). Causes of infection were: hematogenous dissemination in 54%, postoperative wound infection in 28% (17% after open, 11% after arthroscopic procedures). Other causes were: 10% intra-articular steroid injections, 3% diagnostic punctures, and 3% open traumatic injury of the joint. In 78% of the infected joints the causative organism could be identified: Staphylococcus aureus was the most common organism found (42%), followed by streptococci (15%), pneumococci (6%), Escherichia coli (4%), Staphylococcus epidermidis (3%), Borrelia burgdorferi (3%), and others in 5%. In the stage I group only one patient needed repeated arthroscopic irrigation, in the stage II group 52%, and in the stage III group 75%. Open revision for eradication of the infection was necessary in one joint with stage II and in two joints with stage III infection (3%). Two joints of the stage III group needed additional surgery after successful treatment of the infection. The combination of arthroscopic irrigation and systemic antibiotic therapy was able to cure 91% of the affected joints. Open revision was necessary in 4% of joints. The number of arthroscopic procedures and the efficacy of treatment depended on the initial stage of the infection. It is concluded that an arthroscopic staging of the initial joint infection has prognostic and therapeutic consequences.

[Knee endoprosthesis: sports orthopedics possibilities and limitations]. / Knieendoprothetik--Sportorthopädische Möglichkeiten und Einschränkungen.

Many patients would like to resume some sport activities after total knee replacement; however, most recommendations are based on subjective opinion rather than scientific evidence. The following paper presents a literature review of sports after total knee replacement and includes recommendations which are based on biomechanical laws. Most total knee designs show increased conformity near full extension. Beyond a certain knee flexion angle, the conformity ratio decreases due to a reduced femoral radius. Therefore, these designs accept higher loads near full extension than in flexion. In order to recommend suitable physical activities after total knee replacement, both the load and the knee flexion angle of the peak load must be considered. It has been shown that power walking and cycling produce the lowest polyethylene inlay stress of a total knee replacement and seem to be the least demanding endurance activities. Jogging and downhill walking show high inlay stress levels and should be avoided. Hence, for mountain hiking, patients are advised to avoid descents or at least use skipoles and walk slowly downhill to reduce the load on the knee joint. It must also be mentioned that any activity represents additional wear, which may affect the long-term results of total knee replacements. Further clinical studies are necessary to validate the biomechanical investigations.

Transplantation of IL-2-transduced murine bone marrow is associated with dose-dependent toxicity.

OBJECTIVE: The purpose of this study was to investigate the effects of interleukin-2 (IL-2) gene-transduced hematopoietic progenitor cells or cytotoxic function and systemic toxicity following syngeneic bone marrow transplantation. MATERIAL AND METHODS: Marrow of 5-fluorouracil pretreated donor mice were transfected with a retroviral vector containing the murine IL-2 gene and transplanted into lethally irradiated syngeneic hosts. RESULTS: Productive insertion of the IL-2 gene could be demonstrated at various intervals post-transplant without impairment of hematopoietic engraftment. Endogenously augmented IL-2 release resulted in a selective increase in CD4(+), CD8(+), and NK1.1(+) population in spleen and bone marrow, as well as significant cytolytic activity against syngeneic leukemia cells in vitro. Our results also illustrate the interdependence among the magnitude of systemic IL-2 levels, the number of IL-2-transduced cells in the transplant inoculum, and the appearance of systemic toxicity. Infusion of marrow transduced with high-titer, high-expressing IL-2 retrovirus resulted in significant morbidity and mortality in the recipients. Our studies demonstrate that mortality was secondary to severe lymphocytic infiltration of liver and lung, which was associated with increased expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1. Reducing the number of IL-2-transduced cells in the bone marrow inoculum, however, resulted in significantly improved survival with no adverse events being evident during the post-transplant period. CONCLUSION: Delivery of IL-2 to the bone marrow can be achieved by transplantation of genetically modified hematopoietic cells, however, the overall feasibility is strongly influenced by the number of transduced cells in the bone marrow inocolum and/or the expression pattern of IL-2 in vivo.

The effects of conformity and load in total knee replacement.

The effects of different conformity ratios and loads on the ultrahigh molecular weight polyethylene stress levels acting on knee implants were examined using a nonlinear, finite element analysis. The contact condition between a rigid cylinder with a radius of 30 mm and a polyethylene plate was modeled. Nonlinear behavior of polyethylene was assumed. The polyethylene plate was constructed with varying radii, with a minimal thickness of 6 mm and with a width of 40 mm. The ratio of the cylinder radius to the radius of the polyethylene plate was defined as the conformity ratio; a conformity ratio of 0 represented a flat tibial inlay, whereas the highest ratio modeled of 0.99 was nearly conforming. The conformity ratios modeled were 0, 0.2, 0.4, 0.6, 0.7, 0.8, 0.9, 0.95, and 0.99. The loads applied were 1000 N, 2000 N, 3000 N, 4000 N, 5000 N, and 6000 N. The effects of different conformity ratios and loads on the contact area (mm2), the compressive surface stress (MPa), the shear stress (MPa), and the von Mises stress (MPa) were investigated. It was found that all of these parameters were affected by changes to the conformity ratio and to a lesser extent by load changes. That is, increasing the load from 3000 N to 6000 N resulted in a surface and shear stress increase lower than the increase in stress caused by the small change of the conformity ratio from 0.99 to 0.95. The effect of an increasing conformity ratio on the reduction in stress was more pronounced for conformity ratios above 0.8. In addition, the effect of a load increase for a flat tibial inlay was two times greater than for one with near full conformity.

Arthroscopic findings in acute fractures of the ankle.

We have evaluated prospectively the arthroscopic findings in acute fractures of the ankle in 288 consecutive patients (148 men and 140 women) with a mean age of 45.6 years. According to the AO-Danis-Weber classification there were 14 type-A fractures, 198 type B and 76 type C. Lesions of the cartilage were found in 228 ankles (79.2%), more often on the talus (69.4%) than on the distal tibia (45.8%), the fibula (45.1%), or the medial malleolus (41.3%). There were more lesions in men than in women and in general they were more severe in men (p < 0.05). They also tended to be worse in patients under 30 years and in those over 60 years of age. The frequency and severity of the lesions increased from type-B to type-C fractures (p < 0.05). Within each type of fracture the lesions increased from subgroups 1 to 3 (p < 0.05). The anterior tibiofibular ligament was injured with increased frequency from type-B.1 to type-C3 fractures (p < 0.05), but it was not torn in all cases. While lateral ligamentous injuries were seen more often in type-B than in type-C fractures (p < 0.05), no difference was noted in the frequency of deltoid ligamentous lesions. Our findings show that arthroscopy is useful in identifying associated intra-articular lesions in acute fractures of the ankle.

Endurance sports after total knee replacement: a biomechanical investigation.

PURPOSE: No biomechanical evaluation of total knee designs exists for loads occurring during sports activities. It was the purpose of the present study to evaluate the contact stress distribution and contact area of different knee joint designs for loads that occur during four common recreational endurance activities. METHODS: Three different total knee designs were evaluated for loads occurring during cycling (1.2 body weight (BW) at 80 degrees of knee flexion), power walking (4 BW at 20 degrees), hiking (8 BW at 40 degrees), and jogging (9 BW at 50 degrees) using Fuji pressure-sensitive film. The designs consisted of a flat tibial inlay, a curved inlay, and an inlay with mobile bearings. Five measurements were conducted for each load. The pressure sensitive films were scanned and analyzed using an image analysis program. RESULTS: During cycling, the area with stress levels above the yield point of polyethylene (overloaded area) was below 15 mm2 for each design. During power walking, the mobile bearing design showed no overloaded area, whereas it was below 50 mm2 for the flat and curved design. During downhill walking and jogging, more than 140 mm2 were overloaded for each design. CONCLUSIONS: It was concluded that patients after total knee replacement should alternate activities such as power walking and cycling. For mountain hiking, patients are advised to avoid descents or at least use ski poles. Jogging or sports involving running should be discouraged after total knee replacement.

The benefits of wearing a compression sleeve after ACL reconstruction.

PURPOSE: It was the purpose of the present study to examine the possibility of increased muscle coordination after anterior cruciate ligament (ACL) reconstruction through the wearing of a compression sleeve. METHODS: Thirty-six patients were studied who had undergone unilateral ACL reconstruction at least 12 months previously. All subjects were required to perform a 10-cm standing drop jump from an elevated platform onto a force plate, to land on one leg, and thereafter maintain a one-legged balance for 25 s. This task was repeated three times without and three times with an elastic compression sleeve worn on the reconstructed limb. For analysis, the task was partitioned into a landing phase (150 ms), an adjusting phase (10s), and a balancing phase (10s). The peak impact loadings were measured in each direction (Fx, Fy, and Fz) during landing, while force-time integrals (intFz, intFy, and intFz) and root mean square (RMS) error of these forces were calculated for the adjusting and balancing phases. The path length and RMS of the center of pressure coordinates (Ax and Ay) were obtained for the adjusting and balancing phases combined. RESULTS: Drop landings with the bandage produced significantly larger (P < 0.001) peak ground reaction forces in the vertical and anteroposterior direction, suggesting increased subject confidence in their knee. Wearing the knee bandage also enabled the patients to reduce all measured parameters in the anteroposterior direction (rmsFx, intFx, rmsAx) during both the adjusting and balancing phases (P < 0.001 ). A significant reduction in the center of pressure path length further indicated an enhanced steadiness during the one-legged stance. CONCLUSIONS: It was concluded that a compression sleeve improved the total integration of the balance control system and muscle coordination.

Modulation of alloimmune response in vitro by an IgM-enriched immunoglobulin preparation (Pentaglobin).

The mode of action of intravenous immunoglobulins (IVIG) in autoimmune and immunoregulatory disorders is still poorly understood. In vitro, direct effects of IVIG on cytokine release and on cytokine receptors have been described, as well as naturally occurring, neutralizing anticytokine antibodies. The aim of our study was to investigate whether the enrichment in IgM and IgA would have any impact on the in vitro immunomodilatory capacity of IVIG. The preparation tested (Pentaglobin) contains 76% IgG and 12% IgM and IgA, respectively. We could demonstrate a significant inhibition of alloantigen-induced proliferation in the mixed lymphocyte reaction (MLR) even at a Pentaglobin concentration of 1.0 mg/ml. About 10-fold higher concentrations of standard 7S IVIG containing only trace amounts of IgM and IgA were necessary to achieve equivalent suppression of the alloimmune response. Similarly, phytohaemagglutinin (PHA)-induced lymphocyte proliferation was more effectively inhibited by Pentaglobin than by standard 7S IVIG. Cytokine analyses in culture supernatants of MLR provide evidence that Pentaglobin not only modulates interleukin-2 (IL-2), which has already been observed with standard 7S IVIG, but, moreover, modulates interferon-gamma production with a subsequent impact on monocyte-derived tumour necrosis factor-alpha and IL-6 release. Based on these results we conclude that in vitro the IgM- and IgA-enriched Pentaglobin has a more potent immunomodulatory capacity than conventionally used standard 7S IVIG.

[The first dislocation of the shoulder]. / Erstluxation der Schulter.

The classical anterior-inferior dislocation of the shoulder is diagnosed easily by clinical examination and x-ray. The additional lesions like impression fracture at the humerus, avulsion of the anterior rim of the glenoid, lesions of the rotator cuff or neurologic deficits are more difficult to realise. In young patients the redislocation rate is rather high. Indication for surgery is still on debate. Modern diagnostic tools will help to determine additional lesions. More problems are incountered in presence of a posterior dislocation. Those are often overlooked.

[Knee dislocation]. / Knieluxation.

Dislocations of the knee represent a rare but serious injury with an impaired prognosis. The optimal treatment still remains an object of discussion. Within seven years eleven patients have been treated in our hospital after this injury. The review of their reports showed a high incidence of neurovascular damage, loss of motion as well as stiffness. The outcome of the patients with operative treatment was superior to that of the patients with a nonoperative approach. Based on our own results and on the experiences of other authors we present our recommendations in the management of knee dislocations.

CD34+-selected autologous peripheral blood stem cell transplantation (PBSCT) in patients with poor-risk hematological malignancies and solid tumors. A single-centre experience.

Between July 1994 and December 1996, PBSC were mobilized in 28 patients with poor-risk hematological malignancies and solid tumors. CD34+ cells were positively immunoselected using the Ceprate CS System. By December 1996, 22 patients had been reinfused with a median of 3.325 (0.078-9.5) x 10(6)/kg CD34+ cells. In three patients unselected back-up PBSC had to be transfused along with selected CD34+ cells because of a CD34+ cell number <0.5 x 10(6)/kg. G-CSF (10 microg/kg) was started on day +1 and all patients engrafted within a median day number of 12 (range, 10-22) until leukocytes >1.0 x 10(9)/l and a median day number of 56 (range, 10-180) until platelets >20.0 x 10(9)/l (ie platelet transfusion independence). Time to leukocyte and platelet recovery was significantly shorter in patients receiving >2.0 x 10(6)/kg purified CD34+ cells as compared to patients reinfused with <2.0 x 10(6)/kg CD34+ cells. The hematopoietic recovery time was similar to that of 18 historical control patients treated with unseparated ABMT +/- PBSCT with the exception of a significantly faster leukocyte engraftment in patients receiving >2.0 x 10(6)/kg CD34+ cells and a significantly delayed platelet recovery time in patients receiving <2.0 x 10(6)/kg purified CD34+ cells. There was a trend for a better overall survival and a lower probability of progression/relapse as compared to the historical controls. We observed five episodes of serious opportunistic infections (three pulmonary fungal infections, two cases of cryptosporidiosis) after the take. Four of these patients had been reinfused with <2.0 x 10(6)/kg CD34+ cells probably indicating a delayed immune reconstitution after CD34+-selected PBSCT.

Dendritic cells generated from blood precursors of chronic myelogenous leukemia patients carry the Philadelphia translocation and can induce a CML-specific primary cytotoxic T-cell response.

Dendritic cells (DC) are professional antigen-presenting cells specialized in the initiation of primary immune responses. We were interested to know whether mature DC can be grown in vitro from peripheral blood mononuclear cells (PBMC) of patients with chronic myelogenous leukemia (CML), and whether they carry the Philadelphia (Ph) translocation. Using a method recently described, DC were generated from PBMC precursors of 12 patients with CML using GM-CSF, IL-4, and monocyte-conditioned medium. DC exhibited the typical morphology with thin cytoplasmatic processes and expressed high levels of MHC class II, CD86, and CD83 typical for mature DC. After sorting with the monoclonal antibody CD83, a cell population of more than 95% CD83 positive cells was obtained. The presence of the Ph translocation was analyzed in these cells, in PBMC, lymphoblastoid cell lines (LCL), and in phytohemagglutinin (PHA)-induced T blasts from the same patients by fluorescence in situ hybridization (FISH). In contrast to all other cells analyzed, the vast majority of DC (95.9 +/- 0.7%) displayed the Ph translocation, irrespective of disease stage or therapy. PBMC were predominantly positive for the Ph chromosome (67.6 +/- 7.3%), whereas only 11.4 +/- 1% of the B cells and 4.4 +/- 1.1% of the PHA blasts carried the Ph translocation. Using such leukemic DC as antigen-presenting cells, a primary CML-directed cytotoxic immune response in vitro was obtained, as shown by the specific recognition of Ph chromosome positive cells. We conclude that DC can be generated from blood progenitors of CML patients in vitro and exhibit, to a large extent, the Ph translocation. Such DC, which in a preliminary experiment have been able to induce a primary CML-directed cytotoxic immune response in vitro, might be ideal candidates for adoptive immunotherapy either by direct transfer of DC for in vivo generation of a T-cell response or by in vitro generation of CML-specific cytotoxic autologous or HLA-matched normal T-cell clones for use in vivo.