CD3+ lymphocytosis in the peri-implant membrane of 222 loosened joint endoprostheses depends on the tribological pairing.

Background and purpose - The most frequent cause of arthroplasty failure is aseptic loosening-often induced by particles. Abrasion material triggers inflammatory reactions with lymphocytic infiltration and the formation of synovial-like interface membranes (SLIM) in the bone-implant interface. We analyzed CD3 quantities in SLIM depending on articulating materials and possible influences of proven material allergies on CD3 quantities. Patients and methods - 222 SLIM probes were obtained from revision surgeries of loosened hip and knee arthroplasties. SLIM cases were categorized according to the SLIM-consensus classification and to the particle algorithm. The CD3 quantities were analyzed immunohistochemically, quantified, and correlated to the particle types. Results - Metal-metal pairings showed the highest CD3 quantities (mean 1,367 counted cells). CD3 quantities of metal-polyethylene (mean 243), ceramic-polyethylene (mean 182), and ceramic-ceramic pairings (mean 124) were significantly smaller. Patients with contact allergy to implant materials had high but not statistically significantly higher CD3 quantities than patients without allergies. For objective assessment of the CD3 response as result of a pronounced inflammatory reaction with high lymphocytosis (adverse reaction), a defined CD3 quantity per high power field was established, the "CD3 focus score" (447 cells/0.3 mm2, sensitivity 0.92; specificity 0.90; positive predictive value 0.71; negative predictive value 0.98). Interpretation - The high CD3 quantities for metal-metal pairings may be interpreted as substrate for previously described adverse reactions that cause severe peri-implant tissue destruction and SLIM formation. It remains unclear whether the low CD3 quantities with only slight differences in the various non-metal-metal pairings and documented contact allergies to implant materials have a direct pathogenetic relevance.

Mitoxantrone-iron oxide biodistribution in blood, tumor, spleen, and liver--magnetic nanoparticles in cancer treatment.

BACKGROUND: Magnetic drug targeting is a new treatment principle for tumors using cytostatics coupled to ferromagnetic nanoparticles and extracorporeal magnets. Higher concentrations in tumor tissue with lower systemic concentrations and without damage of healthy organs should be achieved. MATERIALS AND METHODS: n = 42 adult Wag/Rij rats were transfected with rhabdomyosarcoma R(1)H in their right gastrocnemius muscle. In the biodistribution trial (n = 36) concentrations of mitoxantrone-iron oxide with and without an extracorporeal 0.6 tesla magnet and regular mitoxantrone were measured in plasma and tumor tissue for one- and two-dose administration. In the plasma iron trial (n = 6) iron concentrations were measured in plasma before, during, and up to 30 min after drug administration. Seven days after the trial liver, spleen and tumor samples were obtained and histologically assessed. RESULTS: Mitoxantrone iron-oxide concentration in plasma was significantly (P < 0.05) lower when a magnet was placed over the tumor area and as low as uncoupled mitoxantrone. Mitoxantrone concentration in tumor tissue was always significantly higher with magnetic drug targeting when compared with uncoupled mitoxantrone. Two doses resulted in drug accumulation in tumor tissue. Plasma iron concentrations rose when the drug was first administered. Plasma levels fell below the starting level with a magnet applied. A rebound phenomenon with rising iron concentrations was observed after the magnet was removed. Tumors showed fresh necrosis and liver and spleen had detectable iron depositions but no necrosis 7 d after treatment. No allergies or toxic reactions were observed. CONCLUSIONS: We showed that magnetic drug targeting achieves higher concentrations of cytostatics in tumor tissue compared with blood. During magnetic drug targeting, iron particles are quickly sliced and kept in the tumor area. Organs of the reticuloendothelial system are not affected by cytostatic damage.

Computer-assisted validation of the synovitis score.

Histopathological examination of synovial specimens can contribute to the diagnosis of chronic joint diseases. A so-called synovitis score has been introduced as a standardised grading system, based on the semi-quantitative evaluation of the three determining features of chronic synovitis: enlargement of synovial lining, density of synovial stroma and inflammatory infiltrate, giving a score between 0 and 9. The present study examines the reliability of this procedure by comparison with exact measurements using computer-assisted image analysis (CAIA). Seventy-one synovial specimens from patients with osteoarthritis (OA, n=22), psoriatic arthritis (PsA, n=7), rheumatoid arthritis (RA, n=35) and from a control group (Co, n=7) were evaluated using both the synovitis score and CAIA. The measurements were transformed to semi-quantitative values analogous to the synovitis score. The differences between the transformed CAIA scores and the pathologist's scores were 0 or +/-1 in 40 cases, whereas in 31 cases the difference was greater than 1 (correlation coefficient r=0.725). The CAIA scores differed significantly between Co and RA cases (p=0.000) as well as between OA and RA (p=0.000). We conclude that the synovitis score was validated by CAIA and can be regarded a reliable grading system that contributes to the diagnostic procedure of chronic joint inflammation.

Molecular case report: IgVH analysis in acute humoral and cellular liver allograft rejection suggests a selected accumulation of effector B cells and plasma cells.

Acute cellular (CLR) and humoral liver allograft rejection (HLR) are the most important immunological obstacles to successful liver transplantation. In HLR, serum antibodies play the central pathogenetic role. In CLR, CD3+ T lymphocytes drive the destructive immune response. Although CLR and HLR show different clinical symptoms and can be kept apart in most cases, they share histomorphological similarities. In CLR, hepatic B lymphocytes and plasma cells as well as B-cell-activating cytokines have recently been described, indicating that, in addition to T cells, antibody-mediated mechanisms might be involved. To analyze the impact of hepatic B cells in CLR and HLR, the immunoglobulin (Ig) variable (V)-region gene repertoire was determined from tissue of one case of CLR and one case of HLR. Complement deposits and lymphocytic infiltrate were determined using immunohistochemistry. T cells, B lymphocytes and plasma cells could be detected in both cases, whereas C3c and C4d deposits could only be demonstrated in the HLR case. The molecular analysis of 63 V-region genes showed that B cells in both allografts expressed selected V-gene repertoires. All sequences differed from the putative germline sequences by multiple somatic mutations. This suggests a clonal expansion of selected effector B cells in the portal tracts of liver allografts. Locally accumulated B cells and their antibodies might be involved in IgG-mediated complement activation in CLR and HLR.

Portal capillary C4d deposits and increased infiltration by macrophages indicate humorally mediated mechanisms in acute cellular liver allograft rejection.

Almost no data exist concerning the role of antibody-mediated mechanisms in human acute cellular liver allograft rejection (ACR). Therefore, the aim of this study was to determine whether ACR is associated with depositions of complement split products and increased infiltration by B-lymphocytes, plasma cells and macrophages. A total of 35 liver biopsy specimens (ACR n=22, controls n=13) were analyzed by immunohistochemical single and double staining. The average numbers of CD 20(+), CD 38(+) and CD 68(+) cells per portal tract were established while the presence of C4d and C3d deposits was evaluated semiquantitatively. Significantly greater numbers of CD 20(+) (P=0.029) and CD 38(+) (P=0.014) cells were found in the ACR specimens than in the control specimens. Additionally, 50% of patients diagnosed with ACR showed C4d deposits along portal capillaries, which was associated with a significantly increased portal infiltration by macrophages (P=0.007). Taken together these results support the involvement of humorally mediated mechanisms in some cases of ACR.

Description of B lymphocytes and plasma cells, complement, and chemokines/receptors in acute liver allograft rejection.

BACKGROUND: Although antibody mechanisms play a pathogenetic role in liver allograft rejection, no data exist on B lymphocytes, plasma cells, complement, and chemokines in rejected liver tissue. METHODS: Liver biopsy specimens from 25 patients with acute allograft rejection (AR) (rejection activity index, RAI score: 1-9) were analyzed by immunohistochemistry (IH) and reverse transcriptase-polymerase chain reaction (RT-PCR) and compared with biopsy specimens taken prior to implantation (PI). The number of CD20 and CD138 cells was evaluated, and the presence and abundance of the chemokines macrophage inflammatory protein (MIP)-3alpha, CXCL9, CXCL10, CXCL11, CXCL12, and their receptors CCR-6, CXCR3, and CXCR4 were examined. Complement depositions were visualized by C4d IH. RESULTS: The numbers of B lymphocytes (P=0.002) and plasma cells (P=0.022) were significantly higher in AR biopsy specimens compared with PI biopsy specimens. MIP-3alpha and CCR-6 cells were detected in the portal fields of all AR biopsy specimens. IH double staining revealed a colocalization of MIP-3alpha/CD20 cells; C4d deposits could be demonstrated along the portal capillaries. All examined chemokines and receptors could be detected in normal liver tissue and in AR biopsy specimens by RT-PCR and semiquantitative RT-PCR, demonstrating an overexpression of CXCL10 and -11. CONCLUSIONS: The significant increase of B lymphocytes and plasma cells during acute rejection, together with the lack of a significant increase of proliferating cells, indicates that the migration of B lymphocytes and plasma cells-promoted by the expression of B-cell activating chemokines/receptors-plays a key role in acute liver rejection. The C4d deposits along the portal capillaries indicate a humorally mediated alloresponse caused by the accumulated B and plasma cells.

Patients' satisfaction with different modalities of prostate cancer therapy--a retrospective survey among 634 patients.

AIM: To assess the overall impact of the most common contemporary prostate cancer therapies (radical prostatectomy, percutaneous irradiation, brachytherapy, hormonal therapy) with regard to physical and psychological well-being, as well as to general patient satisfaction. PATIENTS AND METHODS: In October 2006, a questionnaire focused on patients' opinions and satisfaction regarding their previous prostate cancer therapies was published in a patient cancer journal (Krebsmagazin). Results were collected until March, 2007 and analyzed using Wilcoxon and Student's t-tests. RESULTS: Answers were obtained from 634 patients (radical prostatectomy: 61%; percutaneous irradiation: 17%; brachytherapy: 2%; hormonal therapy: 15%; other/combined: 5%). Concerning late side effects and convenience of treatment, 96% of all patients who had undergone percutaneous irradiation were very satisfied with their choice and would choose the same therapy again (brachytherapy: 93%; hormonal therapy: 84%; radical prostatectomy: 79%). Erectile dysfunction with inability to perform sexual intercourse was reported by 32% of all patients who underwent percutaneous irradiation (brachytherapy: 21%; hormonal therapy: 63%; radical prostatectomy: 52%). No sexual problems at all were reported by 22% of patients who underwent percutaneous irradiation (brachytherapy: 21%; hormonal therapy: 13%; radical prostatectomy: 4%). With regard to psychological and physical deficits (fear; depression; urinary, bowel, erectile dysfunction; hormonal disorders), percutaneous irradiation was superior to the other treatment options (no deficits: percutaneous irradiation; 49%; brachytherapy: 36%; hormonal therapy: 17%; radical prostatectomy: 15%). CONCLUSION: Radiotherapy showed superior results regarding patient convenience and satisfaction in comparison to hormonal therapy and surgery in the treatment of patients with prostate cancer.