Expression of adhesion molecules on synovial fluid and peripheral blood monocytes in patients with inflammatory joint disease and osteoarthritis

OBJECTIVE: To determine the presence of adhesion molecules on monocytes/macrophages (Mphi) from peripheral blood (PB) and synovial fluid (SF) in patients with osteoarthritis (OA) and inflammatory joint diseases (rheumatoid (RA) and reactive arthritis (ReA)) in order to improve our understanding of the possible mechanisms underlying the inflammatory process. METHODS: Whole blood and SF cells were stained with monoclonal antibodies against CD11a (LFA-1), CD15 s (sialyl-Lewis X), CD44, CD54, VLA-4, and HLA-DR counterstained with anti-CD14 antibodies as a Mphi marker for dual fluorescence analysis by flowcytometry. RESULTS: On PB-Mphi, CD15s was markedly increased in both RA as well as ReA compared with OA. Furthermore, in the PB LFA-1, CD44, and HLA-DR showed a higher surface density on Mphi in ReA than in OA. Comparison between SF and PB showed significantly higher CD44 and CD54 expression on SF-Mphi. These molecules play an important part in lymphocyte-Mphi interaction. CONCLUSION: In PB from patients with inflammatory joint diseases, Mphi are activated, allowing recruitment into the synovial compartment. These disorders, in contrast with OA seem to be "systemic" in nature. Within the SF, different adhesion molecules are expressed on CD14(+) Mphi as compared with PB.     

Clinical behavior of implant infections due to Staphylococcus epidermidis

Surgical implants and other foreign material are increasingly used in modern medicine to restore or to improve the function of the human body. Infection of an implant is associated with considerable morbidity due to frequent hospitalizations, surgery and antimicrobial treatment. The underlying mechanism is the formation of a bacterial biofilm on the surface of the implanted body. The recognition and diagnosis of implant infections is essential for further therapy and, above all, the decision to remove and exchange the implant. METHODS: We compared the data of 60 patients with implant infections with those of 60 patients with transient bacteremia caused by Staphylococcus epidermidis. The pathogens isolated from blood were characterized with regard to antimicrobial susceptibility and formation of biofilms using a static microtiter plate model. Wild type skin isolates from non-hospitalized healthy volunteers served as control with regard to antimicrobial susceptibility and biofilm formation. RESULTS: Clinical signs and symptoms, underlying diseases and outcome were not different in either group. However, patients with implant infection had fever over a longer time (mean 12 days versus 3 days, respectively, p < 0.05) and more often positive blood cultures than patients with transient bacteremia (3.1 versus 1.2, p < 0.05). Thrombocytopenia was observed in patients with implant infections but not in patients with transient bacteremia (p < 0.05). Biofilms were formed in 86.4 % of the isolates in implant infection, in 88.8 % in transient bacteremia and in 76.9 % of the isolates from healthy volunteers (not significant). Multi-resistance to penicillin, oxacillin, erythromycin, clindamycin, ciprofloxacin and trimethoprim was more common in the hospital strains than in the wild type strains (75.6 % versus 48.7 %, p < 0.05). CONCLUSIONS: The clinical features of implant infections are indistinguishable from those of transient bacteremia. Persisting fever and multiple blood culture yielding the growth of skin flora bacteria are strong indicators for infection of implanted material. Biofilm formation and antimicrobial multi-resistance, as common in implant infection as in transient bacteremia, seem to be accessory factors in infections due to Staphylococcus epidermidis.     

Chondrocyte number and proteoglycan synthesis in the aging and osteoarthritic human articular cartilage

OBJECTIVE: To correlate the number of chondrocytes in healthy and osteoarthritic human articular cartilage with age, and to evaluate the influence of donor age on total proteoglycan synthesis. METHODS: Chondrocytes were isolated from human articular cartilage derived from hip joints with and without osteoarthritic lesions. The cell number was normalised to cartilage sample wet weight. In addition, the influence of age on chondrocyte numbers was assessed histomorphometrically. Chondrocytes were grown as monolayer cultures for seven days in a chemically defined serum-free basal medium. Total proteoglycan synthesis was measured by [(35)S]sulphate incorporation into newly synthesised macromolecules. RESULTS: Chondrocyte numbers in healthy cartilage decreased significantly with advancing age (r = -0.69, p<0.0001). In contrast to healthy specimens, chondrocyte numbers were decreased in osteoarthritic cartilage irrespective of and unrelated to age, and differed markedly, by an average of 38%, from the cell numbers found in healthy individuals (p<0.0001). Regarding synthesis of matrix macromolecules, no dependence on patients' age, either in healthy or in osteoarthritic specimens, could be observed. CONCLUSIONS: Under the experimental conditions employed, chondrocytes from healthy and osteoarthritic joints synthesised comparable amounts of cartilage macromolecules, independent of age or underlying osteoarthritic disease. Thus the decrease in chondrocyte number in aging and osteoarthritic joints could be a crucial factor in limiting tissue replenishment.     

Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners.

To elucidate the mechanism of the t(14;18)(q32;q21) chromosomal translocation found in follicular lymphoma, we examined the structure of both derivative (der) chromosomal breakpoints as well as their germ-line predecessors. We noted that chromosome segment 18q21 was juxtaposed with immunoglobulin heavy (H) chain gene diversity (DH) regions on all five der(18) chromosomes we examined, and we confirmed the juncture with immunoglobulin H-chain gene joining (JH) regions on the der(14) chromosome. However, the t(14;18) was not fully reciprocal in that chromosome 14 DNA between the DH and JH regions was deleted. Furthermore, extra nucleotides, reminiscent of "N" segments, were present at the der(14) and possibly der(18) junctions. This indicates that despite the mature B-cell phenotype of follicular lymphoma, the t(14;18) occurs during attempted DH-JH joining, the earliest event in immunoglobulin rearrangement in a pre-B-cell. Our detailed analysis of the germ-line 18q21 region indicated that most breakpoints clustered within a 150-base-pair major breakpoint region. However, we found no evidence for evolutionarily conserved immunoglobulin-like recombinational signals at 18q21, arguing against a role for immunoglobulin recombinase in chromosome 18 breakage. Instead, a direct repeat duplication of chromosome 18 sequences was discovered at both chromosomal junctures, typical of the repair of a naturally occurring staggered double-stranded DNA break. These results prompt a translocation model with illegitimate pairing of a staggered double-stranded DNA break at 18q21 and an immunoglobulin endonuclease-mediated break at 14q32 and with N-segment addition, repair, and ligation to generate der(14) and der(18) chromosomes.     

Community-acquired pneumonia in children in Lambarene, Gabon

Community-acquired pneumonia (CAP) accounts for more than two million deaths per year in children < 5 years of age. Recognition of pathogens is vital for guiding antibiotic treatment. In Gabon, no epidemiologic data on childhood CAP were available to help guide antibiotic therapy. We conducted a prospective, hospital-based, cross-sectional survey at the Albert Schweitzer Hospital, Lambarene, Gabon, to assess the importance of atypical organisms (Chlamydia pneumoniae, Mycoplasma pneumoniae, Bordetella pertussis, and Legionella pneumophila) and Streptococcus pneumoniae in the etiology of CAP in children by means of real-time polymerase chain reaction, cell culture, and serology. Collectively, atypical bacteria accounted for 11% of cases with a special emphasis on B. pertussis, accounting for 6% of cases. Clinical differentiation of atypical from typical pneumonia in children remains challenging. Molecular diagnostic methods offer fast and highly sensitive diagnostic tools and would be able to help guide antimicrobial therapy in rural areas where follow-up is difficult.     

Bacterial adherence to different components of total hip prosthesis in patients with prosthetic joint infection

Purpose

The purpose of our study was to evaluate and quantify the bacterial adherence to the different components of total hip prosthesis.

Methods

The bacterial load of 80 retrieved hip components from 24 patients was evaluated by counting of colony-forming units (CFU) dislodged from component surfaces using the sonication culture method.

Results

Micro-organisms were detected in 68 of 80 explanted components. The highest bacterial load was detected on the polyethylene liners, showing a significant difference in distribution of CFU between the liner and metal components (stem and cup). Staphylococcus epidermidis was identified as the pathogen causing the highest CFU count, especially from the polyethylene liner.

Conclusions

Results of our study confirm that sonicate culture of the retrieved liners and heads, which revealed the highest bacterial loads, are reliable and sufficient for pathogen detection in the clinical diagnostic routine.     

Incomplete lupus erythematosus: results of a multicentre study under the supervision of the EULAR Standing Committee on International Clinical Studies Including Therapeutic Trials (ESCISIT)

OBJECTIVE: Patients characterized with antinuclear antibodies (ANA) and disease symptoms related to one organ system can be described as having incomplete systemic lupus erythematosus (SLE). The aim of this multicentre study was to describe the outcome of these so-called incomplete SLE patients. Two aspects of the outcome were studied: (i) the disease course, defined by the presence or absence of clinical symptoms; and (ii) the number of patients that eventually developed full SLE. METHODS: Outcome parameters were the ACR criteria, the SLE disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM) and the requirement for treatment. In 10 European rheumatology centres, patients who had been evaluated in the last 3 months of 1994 and had been diagnosed as having incomplete SLE on clinical grounds for at least 1 yr were included in the study. All 122 patients who were included in the study were evaluated annually during 3 yr of follow-up. RESULTS: Our results are confined to a patient cohort defined by disease duration of at least 1 yr, being under clinical care at the different centres in Europe. These patients showed disease activity that was related mostly to symptoms of the skin and the musculoskeletal system, and leucocytopenia. During the follow-up, low doses of prednisolone were still being prescribed in 43% of the patients. On recruitment to the study, 22 of the 122 incomplete SLE patients already fulfilled the ACR criteria for the diagnosis of SLE. In the 3 yr of follow-up only three patients developed SLE. CONCLUSIONS: A high proportion of patients in our cohort defined on clinical grounds as having incomplete SLE eventually showed disease activity defined by the SLEDAI as well as ECLAM. However, only three cases developed to SLE during the follow-up. This suggests that incomplete SLE forms a subgroup of SLE that has a good prognosis.     

HLA-DR antigens in systemic lupus erythematosus: association with specificity of autoantibody responses to nuclear antigens.

HLA-DR antigens and autoantibodies to the nuclear or cytoplasmic antigens Ro/SSA, La/SSB, Sm, and RNP were determined in North American and Austrian patients with systemic lupus erythematosus (SLE). Analysis of the association of antibodies to these ribonucleic acid (RNA)-protein antigens with HLA-DR antigens showed that HLA-DR3 was related to the presence of anti-Ro/SSA or anti-La/SSB, or both. In contrast, anti-Sm or anti-RNP, or both were associated with HLA-DR4. HLA-DR5 was associated with absence of these autoantibodies. The data extend evidence for the complexity and heterogeneity of SLE. Moreover, they indicate that, in SLE, genes linked to those coding for HLA-DR antigens, are related to the specificity of autoantibody responses rather than to the primary immunological abnormalities of this disorder.     

Survival and quality of life in 23 patients with severe aplastic anemia treated with bone marrow transplantation (BMT)

Summary Survival and quality of life are reported in 23 pretransfused patients with severe aplastic anemia (SAA) who underwent bone marrow transplantation (BMT). The projected survival is 76% with 18 of 23 patients being alive 332 to 1677 days post graft (median: 842). 5 patients died between day 4 and 416. 12 of 17 patients at risk developed chronic graft versus host disease (GVH-D). 4 of these patients have a diminished quality of life due GVH-D related disabling manifestations. Autologous haemopoietic recovery was excluded in all patients by the demonstration of haemopoietic chimerism. We recommand age-adapted rejection prophylaxis; such strategy may help to diminish disabling graft versus host disease in otherwise haematologically reconstituted survivors.National Blood Group Reference Laboratory (WHO), National Tissue Typing Reference Laboratory (Council of Europe)     

Effects of enalapril on disseminated intravascular thrombin formation during systemic inflammation

BACKGROUND: Tissue factor (TF), the main trigger of coagulation is important in the propagation of cardiovascular diseases. Based on an in vitro study, we hypothesised that enalapril may blunt the endotoxin-induced, TF-triggered coagulation in humans. METHODS: In a randomised, controlled trial, 30 healthy male volunteers received 2 ng/kg of lipopolysaccharide (LPS) after pre-treatment with placebo or enalapril for 5 days or with enalapril 2 h before LPS infusion. RESULTS: Infusion of LPS increased interleukin-6 levels 400 fold, and induced a 10-fold increase in prothrombin fragment, a fourfold increase in D-dimer, and a fivefold increase in plasmin-antiplasmin complexes. However, pre-treatment with enalapril did not blunt LPS-induced coagulation. CONCLUSIONS: Our trial provides evidence against a modulatory role of angiotensin converting enzyme in LPS-induced, TF-triggered coagulation.