Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study

Objective: To compare the efficacy and safety of treatment with infliximab plus methotrexate with methotrexate alone in methotrexate-naive patients with active psoriatic arthritis (PsA). Methods: In this open-label study, patients 18 years and older with active PsA who were naive to methotrexate and not receiving disease-modifying therapy (N=115) were randomly assigned (1:1) to receive either infliximab (5 mg/kg) at weeks 0, 2, 6 and 14 plus methotrexate (15 mg/week); or methotrexate (15 mg/week) alone. The primary assessment was American College of Rheumatology (ACR) 20 response at week 16. Secondary outcome measures included psoriasis area and severity index (PASI), disease activity score in 28 joints (DAS28) and dactylitis and enthesitis assessments. Results: At week 16, 86.3% of patients receiving infliximab plus methotrexate and 66.7% of those receiving methotrexate alone achieved an ACR20 response (p<0.02). Of patients whose baseline PASI was 2.5 or greater, 97.1% receiving infliximab plus methotrexate compared with 54.3% receiving methotrexate alone experienced a 75% or greater improvement in PASI (p<0.0001). Improvements in C-reactive protein levels, DAS28 response and remission rates, dactylitis, fatigue and morning stiffness duration were also significantly greater in the group receiving infliximab. In the infliximab plus methotrexate group, 46% (26/57) had treatment-related adverse events (AE) and two patients had serious AE, compared with 24% with AE (13/54) and no serious AE in the methotrexate-alone group. Conclusions: Treatment with infliximab plus methotrexate in methotrexate-naive patients with active PsA demonstrated significantly greater ACR20 response rates and PASI75 improvement compared with methotrexate alone and was generally well tolerated. This trial is registered in the US National Institutes of Health clinicaltrials.gov database, identifier NCT00367237

Evaluation of the campyslide agglutination test for confirmatory identification of selected Campylobacter species.

The utility of a rapid latex slide agglutination test (Campyslide; BBL Microbiology Systems, Cockeysville, Md.) in detecting selected Campylobacter spp. was evaluated and compared with that of conventional identification methods. Isolated colonies suggestive of Campylobacter spp. were tested directly from primary selective media after incubation at 42 degrees C under microaerophilic conditions. Stock cultures of Campylobacter jejuni (n = 27) and C. coli (n = 3) were correctly confirmed to the genus level by latex agglutination when tested in pure cultures or isolated from seeded human feces. A total of 50 fresh clinical isolates of Campylobacter spp. (45 C. jejuni and 5 C. coli) were examined, with complete agreement observed between the latex test and conventional methods. Of 173 non-Campylobacter isolates tested from primary plates, only 1 rough strain of Pseudomonas aeruginosa produced a false-positive result. Although the manufacturer recommends a 30-min antigen extraction, 1 or 5 min was found to be sufficient. Also, confirmation could be achieved within 24 h of inoculation of clinical specimens, 2 days earlier than with conventional methods

Ultrastructural study of mode of entry of Chlamydia psittaci into L-929 cells.

The entry of Chlamydia psittaci into L-929 cells was studied morphologically by transmission electron microscopy and quantitatively by a method that discriminates between attachment and uptake. Upon adsorption of 3H-labeled elementary bodies (EBs) to host cells at 4 degrees C, the EBs bound efficiently to the L-cell surface. Binding reached an equilibrium level of 55% in 3 h. Ultrastructural analysis revealed that EBs were bound preferentially to the tips and sides of microvilli at this temperature. The EBs were also observed in coated pits located at the bases of microvilli and along smooth surfaces of the host cell. No internalization was observed at 4 degrees C. When cells with prebound 3H-labeled EBs were warmed to 37 degrees C, the EBs rapidly became resistant to proteinase K removal (half time = 5 min), indicating ingested chlamydiae. At 37 degrees C, the EBs were internalized within tightly bound vesicles surrounded by an electron-dense coat of fibrillar material. EBs were also present in smooth-surfaced pits and vesicles of the host cell. Using alpha 2-macroglobulin coupled to colloidal gold (a known marker for receptor-mediated endocytosis), we observed that the entry of EBs into cells via coated pits was identical in appearance to the internalization of alpha 2-macroglobulin. Also, when the two ligands were mixed together, they could be seen within the same coated pits and were cointernalized within endocytic vesicles of the host cell. These results suggest that C. psittaci can enter nonprofessional phagocytic cells by a pathway which is similar to that of receptor-mediated endocytosis of many physiologically important macromolecules, bacterial toxins, and viruses

Ultrastructural study of endocytosis of Chlamydia trachomatis by McCoy cells.

The entry of Chlamydia trachomatis into McCoy cells (fibroblasts) was studied by transmission electron microscopy. On adsorption of elementary bodies (EBs) to host cells at 37 degrees C, the EBs were bound primarily to preexisting cell-surface microvilli. They were also observed in coated pits located at the bases of the microvilli and along smooth surfaces of the host cells and were internalized within coated vesicles at this temperature. Postembedding immunogold labeling on Lowicryl thin sections with anti-clathrin antibody as the primary reagent revealed the gold marker localized in pits and vesicles containing chlamydiae. Some EBs were present in smooth-surfaced invaginations at or near the bases of microvilli and in vesicles devoid of distinguishable coat material. A similar entry process was observed with centrifugation-assisted inoculation of EBs onto the McCoy cells. Individual EBs were initially internalized into tightly bound endocytic vesicles. However, within 1 to 3 h postinfection, multiple C. trachomatis EBs were observed in large, loosely bound vesicles. Evidence suggests that vesicles containing C. trachomatis may have fused with one another early in the infectious process. These results indicate that chlamydiae can exploit the specific process of adsorptive endocytosis for entry into host cells and for translocation to a given intracellular destination, which may be different for each species