Early gain in pain reduction and hip function, but more complications following the direct anterior minimally invasive approach for total hip arthroplasty: a randomized trial of 100 patients with 5 years of follow up.

Background and purpose - The minimally invasive direct anterior (DA) approach for total hip arthroplasty (THA) is supposed to reduce surgical tissue trauma. We hypothesized that patients operated with the DA technique would have less postoperative pain and better hip function compared with a group operated with a conventional direct lateral (DL) approach. Patients and methods - 100 patients with hip osteoarthritis scheduled for THA were equally randomized to surgery through either DA or DL. Pain was assessed on a VAS scale, hip function with TUG, 10mWT, HHS, and quality of life with EQ-5D. Patients were followed up after the first 3 days, 8 weeks, and at 1 and 5 years postoperatively. Results - The DA group registered less pain with activity on the second day (VAS 42 vs. 55), performed TUG 6 seconds faster on the third day and had 8 points higher HHS and higher EQ-5D index (0.86 vs 0.78) at 8 weeks; all differences were statistically significant. No clinically relevant differences between groups in pain, hip function, or quality of life were seen at 1 or 5 years. 7 surgical approach related complications appeared in the DA group, none in the DL. Interpretation - The results indicate that the presumably less traumatic approach results in reduced immediate postoperative pain and better hip function and higher quality of life in the early postoperative period. However, this positive effect is not seen at later time points. Instead, complications appear to be over-represented, thus questioning the use of the method.

The critical role of IL-12p40 in initiating, enhancing, and perpetuating pathogenic events in murine experimental autoimmune neuritis.

Interleukin 12 (IL-12) is a proinflammatory cytokine with important immunoregulatory activities and is critical in determining the differentiation and generation of Th1 cells. For the present study, we investigated the role of endogenous IL-12 in the pathogenesis of experimental autoimmune neuritis (EAN), which is a CD4+ T-cell mediated autoimmune inflammatory disease of the peripheral nervous system. EAN is used as an animal model for Guillain-Barré syndrome of humans. Here, EAN was established in IL-12 p40 deficient mutant (IL-12-/-) C57BL/6 mice by immunization with P0 peptide 180-199, a purified component of peripheral nerve myelin, and Freund's complete adjuvant. In these IL-12-/- mice the onset of clinical disease was delayed, and the incidence and severity of EAN were significantly reduced compared to that in wild-type mice.The former group's clinical manifestations were associated with less P0-peptide 180-199 induced secretion of interferon-gamma (IFN-gamma) by splenocytes in vitro and low production of anti-P0-peptide 180-199 IgG2b antibodies in serum. Fewer IFN-gamma and TNF-alpha producing cells, but more cells secreting IL-4, were found in sciatic nerve sections from IL-12-/- mice, consistent with impaired Th1 functions and response. However, the IL-12 deficiency appeared not to affect P0 peptide 180-199-specific T-cell proliferation. These results indicate that IL-12 has a major role in the initiation, enhancement and perpetuation of pathogenic events in EAN by promoting a Th1 cell-mediated immune response and suppressing the Th2 response. This information augments consideration of IL-12 as a therapeutic target in Guillain-Barré syndrome and other T-cell-mediated autoimmune diseases.

Distribution of leucine-enkephalin in bone and joint tissues.

The distribution and concentration of leu-enkephalin in periosteum, cortical bone, bone marrow and synovial membrane of normal rats were analysed. Periosteum, cortical bone and bone marrow of the rat femurs were collected as well as the ankles. The distribution of leu-enkephalin was analysed by immunoelectron microscopy and the concentration of leu-enkephalin was measured with radioimmunoassay. Immunoelectron microscopy showed that leu-enkephalin is abundant in monocytes of bone marrow, nerve fibers and endothelial cells in the periosteum and also in macrophage-like-cells of the synovial membrane. The concentration of leu-enkephalin measured by RIA showed highest concentration in bone marrow followed by periosteum and cortical bone. The study supports that leu-enkephalin is present and can be quantified in different compartments of bone and joint tissues suggesting that leu-enkephalin may be involved in the physiological regulation of nociception and immunoregulation.

Decreased IgG production but increased MIP-1beta expression in collagen-induced arthritis in C-C chemokine receptor 5-deficient mice.

Collagen-induced arthritis (CIA) is a widely used model of human rheumatoid arthritis (RA) characterized by chronic inflammation of the synovial joints. The pathogenesis of RA and CIA has not been completely defined, but both involve the recruitment of leukocytes and lymphocytes to the joints and Th1-type cell mediated autoimmune responses. The C-C chemokine receptor 5 (CCR5) is preferentially expressed on Th1 cells and has been strongly implicated in inflammatory process through trafficking of leukocytes and lymphocytes into the sites of inflammation. We investigated the role of the CCR5 in CIA using CCR5 knockout mice (CCR5-/-) in which we analyzed the consequences of CCR5 deficiency for the immune response and inflammation. We found that CCR5-/- mice showed a significant reduction in the incidence of CIA after collagen II (CII)-immunization as compared to wild-type (CCR5+/+) mice. The reduced incidence seen in CCR5-/- mice was associated with these animals having significantly lower IgG levels, especially IgG2a and IgG2b antibodies against CII, as well as an obviously augmented IL-10 production in splenocytes. Overproduction of MIP-1beta in CCR5-deficient mice after CII-immunization may contribute partially to the occurrence of arthritis.

Galanin in adjuvant arthritis in the rat.

OBJECTIVE: To study the concentration changes of galanin in the ankles and spinal cord and to detect the distribution of galanin in different tissues in arthritic rats. METHODS: Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in Freund's incomplete adjuvant at the base of the tail. The concentrations of galanin were measured by radioimmunoassay (RIA) and the distributions of galanin were detected by immunoelectron microscopy (iEM). RESULTS: Measurements were taken on Day 28 after injection. RIA results showed that the concentration of galanin was significantly lower in the ankles and spinal cords of rats with adjuvant arthritis compared to controls. Our iEM results showed a heterogeneous distribution of galanin labelling in different cells and tissue compartments. In arthritic rats, we observed decreased galanin labelling in the sciatic nerve and in macrophage-like cells in the synovial membrane and increased labelling in monocyte lineage cells, polymorphonucleated lineage cells in the bone marrow, fibroblasts in the periosteum, osteoclasts and osteocytes, and lower labelling in osteoblasts compared to controls. CONCLUSION: Galanin is involved in the response to inflammation in adjuvant arthritis and might play a role in the regulation of inflammation and nociception. These findings are in accordance with a biological role of galanin in the development of inflammatory arthritis.

Exogenous soluble tumor necrosis factor receptor type I ameliorates murine experimental autoimmune neuritis.

Tumor necrosis factor (TNF) and its receptor (TNFR) have been strongly implicated in the pathogenesis of autoimmune disease. Soluble cytokine receptors may be shed naturally from cell membranes to inhibit cytokine activity. Experimental autoimmune neuritis (EAN) is a CD4 Th1 cell-mediated animal model of Guillain-Barré syndrome (GBS) in humans. In the present study, we investigated the effects of soluble TNFR type I (sTNFR I) in EAN induced in mice by P0 peptide 180-199 and Freund's complete adjuvant. Our data from two different therapeutic regimens indicate that the administration of sTNFR I effectively ameliorated the clinical and pathological signs of EAN, i.e., decreased its severity, shortened its duration, and reduced inflammatory cell infiltration into the peripheral nervous system. The suppression of clinical EAN was accompanied in vitro by a marked reduction in antigen-specific T-cell proliferation and IFN-gamma synthesis by spleen cells from sTNFR I-treated mice, compared to control mice treated with PBS. These data directly demonstrate a pivotal role for TNF in the development of EAN and also suggest that sTNFR I may have therapeutic potential for alleviating GBS in humans.