Differential apoptotic response of J774 macrophages to alumina and ultra-high-molecular-weight polyethylene particles.

We recently identified apoptosis in in vitro wear particle-stimulated macrophages. The recent explosion of interest in apoptosis lies in the fact that it is under positive and negative regulation through evolutionary conserved biochemical pathways. It may also be possible to modulate macrophage apoptosis in the treatment of periprosthetic osteolysis. The purpose of this study was to compare the macrophage response to identically sized particles of alumina ceramic (Al2O3) and ultra-high-molecular-weight polyethylene (UHMWPE) in terms of TNF-alpha release and induction of apoptosis. J774 mouse macrophages were incubated for 0-24 h in the presence of Al2O3 and UHMWPE particles. TNF-alpha release was measured by ELISA; Poly(ADP-ribose)polymerase (PARP) and caspase-3 expression was analyzed by Western blot; DNA fragmentation (DNA laddering) was visualized on agarose gel containing ethidium bromide. Al2O3 particles induced TNF-alpha release after 4 h incubation with concentrations reaching 483 and 800 pg/ml after 24 h with 125 and 250 particles/macrophage, respectively (control = 161 pg/ml) (P < 0.05 vs. control). The same concentrations of UHMWPE particles induced a much larger and significant TNF-alpha release after only 1 h incubation, increasing up to 6250 pg/ml after 24 h (P < 0.05 vs. control). Western blot analysis demonstrated that the active caspase-3 fragment (17 kDa) and the proteolytic PARP fragment (85 kDa) were expressed after 2 h incubation with 125 and 250 Al2O3 particles/macrophage. The active caspase-3 and the PARP fragment had lower expression and appeared after a longer incubation time (8 h) with 125 and 250 UHMWPE particles/macrophage. Finally, DNA fragmentation (DNA laddering) was observed after 16 h with 125 and 250 particles of Al2O3 per macrophage whereas no laddering was induced by UHMWPE particles even after 24 h incubation. This study shows that although both Al2O3 and UHMWPE particles induce TNF-alpha release, this stimulation was much greater (8-10 times higher) with UHMWPE than Al2O3 (P < 0.05 vs. control). As well, the induction of apoptosis, as measured by activation of caspase-3, PARP cleavage and DNA laddering, is different for these two particles, being faster and more important with Al2O3 than UHMWPE. We hypothesize that the ability of Al2O3 to induce macrophage apoptosis may explain the lower TNF-alpha release observed with these particles and explain the differences seen in osteolysis patterns of ceramic-ceramic (CC) vs. metal-polyethylene (Mpe) articulations. In conclusion, apoptosis may be a major internal mechanism to decrease macrophage activity and may be a desired therapeutic endpoint. The identification of an apoptosis-related pathway in the macrophage response to ceramic particles provides crucial data for a rational approach in the treatment and/or prevention of periprosthetic osteolysis.     

Clictate: A Computer-Based Documentation Tool for Guideline-Based Care

The use of computer-based documentation tools confers many benefits to the delivery of evidence-based health care. We developed Clictate, a structured reporting environment that utilized standard Windows^TM-based data entry constructs and natural language generation. Clictate has been in use for over 3 years by pediatric providers in an ambulatory setting. More than 50% of our providers use Clictate during the patient encounter. This report describes our results to date, and suggests future opportunities for research and development in the area of computer-based documentation.     

Bilaterally coherent tremor resembling enhanced physiological tremor: report of three cases.

The contribution of the central nervous system to tremor pathogenesis is unclear. Poor side-to-side coherence in physiological, essential, and parkinsonian tremors suggests distinct bilateral generators. By contrast, significant bilateral coherence demonstrated in orthostatic tremor and in enhanced physiological tremor (EPT) in patients with persistent mirror movements favours single or closely linked bilateral oscillators. We describe three patients (aged 21-37 years) who developed unusual bilateral postural and kinetic tremors at 6-13 Hz resembling EPT. The tremor involved all limbs, and in two cases the face or jaw, in the absence of other significant neurological features. Significant side-to-side coherence was demonstrated in each case using cross-correlation of electromyographic recordings from homologous muscle pairs. We postulate that these unusual tremors originate from a single brainstem source or from bilateral oscillators closely linked at or below this level.     

Upper cervical ossicles in Down syndrome

Six patients with upper cervical spine ossicles and Down syndrome from a study population of 184 are described. The average age was 20.6 years at the time of diagnosis. Three of the patients were involved in tumbling. Radiographic anatomy of the ossicles and the dens, as well as serial radiographs in three of the six patients, suggest that this represents an avulsion of the upper end of the dens rather than an occipital vertebrae, ossiculum terminale, or os odontoideum, as previously described. The authors advocate restriction of high-risk activities for all patients with Down syndrome.     

Use of a synthetic peptide-based elisa for the diagnosis of infectious mononucleosis and other diseases

A simple enzyme immunoassay has been developed based on measuring antibodies to synthetic peptides corresponding to sequences in the Epstein-Barr nuclear antigen (EBNA). This assay, which is reproducible, quantitative, and simple to perform and interpret, can be an effective tool to aid in the diagnosis of infectious mononucleosis and nasopharyngeal carcinoma.