Highly reduced binding to high and low affinity mouse Fc gamma receptors by L234A/L235A and N297A Fc mutations engineered into mouse IgG2a.

The effects of the Fc silencing mutations such as leucine (L) to alanine (A) substitution at the position 234 and 235 (LALA) and the alanine (A) to asparagine (N) substitution at position 297 (N297A) are well investigated for human IgG. However, the effects of the same two silencing Fc mutations in a mouse IgG backbone are not yet well investigated in respect to binding to mouse Fc gamma receptors (FcγRs), complement and subsequent effector functions. By using a mouse IgG2a tool antibody directed against mouse OX40L, we demonstrate a strongly reduced binding of the two Fc mutants to high and low affinity recombinant and cell expressed mouse FcγRs, when compared to the mouse IgG2a with the wild type (wt) backbone. Reduced FcγR binding by the two investigated Fc mutants could further be confirmed on primary mouse macrophages expressing their native FcγRs. In addition, we reveal that the LALA and N297A mutations in the mIgG2a also slightly reduced binding to C1q of human origin. Thus, here we provide experimental evidence that the two investigated Fc mutations in the mouse IgG backbone lead to similar "silencing" properties as previously demonstrated for the human IgG and thus represent a useful method to alter effector functions in tool antibodies to be used in mouse models.

[Long-term results with the cementless CLS stem in hip replacement]. / Langzeitresultate des unzementierten CLS-Schaftes in der Hüftendoprothetik.

OBJECTIVE: The present work aims at evaluating the clinical and radiological long-term results of the cementless CLS stem in hip replacement. METHOD: Sixty-six consecutively operated patients were examined clinically and radiologically at an average follow-up time of 10.7 (7.6 - 13.8) years. The clinical evaluation was done with the Merle d'Aubigné and the Harris hip scores. The radiological evaluation included the evaluation of radiolucencies as well as the occurrence of heterotopic ossifications. RESULTS: A total of four stems had to be revised (two infections, two periprosthetic fractures). No stem revision had to be done because of aseptic loosening. This results in a survival rate of 94.5% according to Kaplan-Meier. The mean Merle d'Aubigné scores increased from 9.0 preoperatively to 16.0 points at follow-up. The mean follow-up Harris hip score was 87.3 points. Periprothetic osteolytic zones were observed in 45% of the cases, particularly in the Gruen zones 1 and 7. These osteolytic zones were mainly found in connection with cementless polyethylene cups. CONCLUSION: The results of this study confirm the positive short and medium-term results with the CLS stem in a long-term process. The formerly described phenomenon of the residual thigh pain with cementless stems was clearly minimized.

[Blood loss in total hip prosthesis implantation: lateral versus supine position]. / Blutverlust bei Hüfttotalprothesenimplantationen: Seitenlage versus Rückenlage.

We performed a prospective randomized study to determine blood loss differences between supine or lateral patient position, during surgery in elective total hip replacement. Between January and October 1996, 64 consecutive cases of total hip replacements were randomly scheduled for a procedure either in the supine or in the lateral position. Of the 56 cases evaluated, 29 were operated in the supine position (SP) and 27 in the lateral position (LP). The standardized implantations were performed without cement and the blood loss was measured. The calculated loss of Hb on the day of operation was 235 g Hb +/- 17 (mean +/- s.e.) in the SP group and 177 g Hb +/- 14 in the LP group, respectively, (unpaired t-test p = 0.01). The calculated loss of Hb after five postoperative days was 227 g Hb +/- 24 (mean +/- s.e.) in the SP group and 179 g Hb +/- 24 in the LP group, respectively, p < 0.2. The net loss of Hb after five postoperative days was calculated by subtracting all perioperative blood substitutions (Cellsaver, autologous and homologous blood) resulting in 340 g Hb +/- 21 (mean +/- s.e.) in the SP group and 272 g Hb +/- 21 in the LP group, respectively, p = 0.02. The blood loss in primary cementless total hip replacement surgery can be significantly reduced by performing the procedure in the lateral position compared to that in the supine position. The blood loss is limited to the day of operation, as indicated by the stable Hb-levels thereafter.

Radiolucent lines and component stability in knee arthroplasty. Standard versus fluoroscopically-assisted radiographs.

The radiolucent lines and the stability of the components of 66 knee arthroplasties were assessed by six orthopaedic surgeons on conventional anteroposterior and lateral radiographs and on fluoroscopic views which had been taken on the same day. The examiners were blinded as to the patients and clinical results. The interpretation of the radiographs was repeated after five months. On fluoroscopically-assisted radiographs four of the six examiners identified significantly more radiolucent lines for the femoral component (p < 0.05) and one significantly more for the tibial implant. Five examiners rated more femoral components as radiologically loose on fluoroscopically-assisted radiographs (p = 0.0008 to 0.0154), but none did so for the tibial components. The mean intra- and interobserver kappa values were higher for fluoroscopically-assisted radiographs for both components. We have shown that fluoroscopically-assisted radiographs allow more reproducible, and therefore reliable, detection of radiolucent lines in total knee arthroplasty. Assessment of the stability of the components is significantly influenced by the radiological technique used. Conventional radiographs are not adequate for evaluation of the stability of total knee arthroplasty and should be replaced by fluoroscopically-assisted films.

Unusual patterns of glenohumeral joint injuries in adolescent ski-jumpers.

We report on two 16.5-year-old ski-jumpers who sustained unusual glenohumeral joint injuries. The first fell on landing, the other while running out. Neither could give any indications as to the pathomechanics of the injuries, thus illustrating the high speed nature of the trauma.

[Cervico-acetabular impingement after femoral neck fracture]. / Zervikoazetabuläres Impingement nach Schenkelhalsfraktur.

Six cases of femoral neck-acetabular impingement following fracture of the femoral neck are reported. To our knowledge, this complication has not previously been described in the literature. A bony prominence at the level of the former fracture site following primary or secondary valgus position of the femoral head showed a conflict with the acetabular rim causing pain and limited motion. In four patients this impingement was posterior, between the femoral neck and the acetabulum in extension with external rotation, and in two patients it was anterior in flexion with internal rotation. A detailed description of the symptoms, diagnostic procedures and treatment options is presented.

ICLH arthroplasty of the knee: 1968--1977.

The essentially satisfactory results from the ICLH implant as used until 1975 were marred by examples of loosening and sinking of the tibial implant, by patellar pain of varying severity, by wear of the tibial implant caused by fragments of cement and by failure consistently to control the alignment of the leg. This report describes the methods now being used to overcome these complications and gives an account of the success so far achieved.