How have new designs and new types of joint replacement influenced wear behavior?

As the principles of joint arthroplasty become increasingly refined and more widely established, new designs are being developed that require careful evaluation for their propensity to generate wear debris in vivo. In the past several years, new designs intended to improve clinical performance have emerged in both total knee replacement and total spinal disk replacement. Advances in these types of implants have the potential for major clinical impact in the coming decade, due to the large number of patients seeking treatment of knee arthritis as well as back pain, neck pain, and radiculopathy.     

Are there biological markers of wear?

Potential systemic markers of implant wear include products of the wear process (particles and ions) and mediators of the inflammatory reaction that can be induced by wear. Ions from polymers used in arthroplasty are not specific, but high metal ion levels may help identify patients with unexpectedly high wear of metal-on-metal implants. The kinetics of ion production, transport, and excretion are complex, however, so it is currently difficult to interpret the significance of mild elevations in metal ions. Indices of bone turnover (eg, collagen fragments) and mediators involved in the inflammatory reaction to particles (eg, osteoprotegerin, RANKL, interleukins) may be associated with osteolysis, but systemic disorders (eg, osteoarthritis) and the use of medications that influence bone remodeling limit the predictive value of these analytes with respect to the consequences of implant wear. Using genomic and proteomic methods to measure multiple analytes offers promise, but the challenge is to identify markers specifically associated with wear that are not elevated by other conditions that often coexist in this patient population.     

What is the outcome of treatment for osteolysis?

Periprosthetic osteolysis secondary to wear-induced particle generation is a common long-term complication of hip and knee replacement and frequently results in the need for revision surgery. Management of significant bone defects remains a surgical challenge. Surgical intervention must address the wear particle generator (usually, but not always, the bearing surface), the osteolytic defects, and implant-related issues, primarily fixation and alignment. Indications for surgical intervention in the absence of loosening and pain are not well established. In general, patient age and activity level, the location and size of the osteolytic defect, and the clinical record of the implant system will dictate treatment choices.     

How have alternative bearings (such as metal-on-metal, highly cross-linked polyethylene, and ceramic-on-ceramic) affected the prevention and treatment of osteolysis?

Osteolysis is a multifactorial process dependent on surgical technique, implant design, patient factors, and material composition. Alternative bearing surfaces, such as highly cross-linked polyethylene, ceramic-on-ceramic, and metal-on-metal articular surfaces, have been introduced in an attempt to reduce wear and osteolysis following total hip arthroplasty. Intermediate-term follow-up data available suggest that the prevalence and severity of osteolysis may be reduced with these materials compared with conventional metal-on-polyethylene bearing surface couples. However, long-term data are presently unavailable; the future performance of these bearings awaits clinical validation.     

The utility of the Cambridge Behavioural Inventory in neurodegenerative disease

We investigated the utility of the Cambridge Behavioural Inventory (CBI), a carer-completed questionnaire, in a large cohort with Parkinson's disease (PD) (n = 215). In a sub-cohort of 112 patients with PD, the CBI was found to be a valid instrument compared with the Neuropsychiatric Inventory, PDQ-39 and UPDRS, with high internal consistency. Furthermore, in the whole cohort, the CBI was sensitive to changes in behaviour with disease progression. Comparison between CBI scores in PD and other neurodegenerative diseases, including Huntington's disease (HD) (n = 75), Alzheimer's disease (AD) (n = 96) and frontal variant frontotemporal dementia (fvFTD) (n = 64), revealed distinct profiles for each disease. Predominant deficits were "sleep"' and "self care" in PD; "memory" in HD and AD; and "motivation" and "stereotypic behaviours" in fvFTD. The CBI is a robust, easy-to-use and valid instrument, which has the capacity to discriminate between neurodegenerative diseases, and may be of value in monitoring therapeutic interventions.     

Differential regulation of chromogranin B/secretogranin I and secretogranin II by forskolin in PC12 cells.

The factors which regulate the expression of the granin family of secretory proteins have yet to be completely described. The present study investigated the effects of forskolin (FSK), an activator of adenylate cyclase, on the regulation of chromogranin B/secretogranin I (CgB) and secretogranin II (SgII) mRNA levels in rat PC12 cells. PC12 cells were treated with 10 microM FSK for time points up to 48 h and were harvested for cAMP determination, RNA isolation and Northern blot analysis, or fixed in 4% paraformaldehyde for immunocytochemistry. Cellular cAMP levels peaked after two h of FSK treatment and remained elevated for 48 h. Chromogranin B mRNA increased with FSK treatment, reaching a maximum of 7-fold above control after 24 h, while the level of SgII mRNA decreased to a level of 65 +/- 10% of control after 48 h. The effects of FSK on CgB mRNA appear to be mediated by cAMP, as 8-bromo-cAMP (500 microM) resulted in a 2.8-fold increase in CgB mRNA, and H-89 (30 microM), a selective inhibitor of cAMP-dependent protein kinase, reduced the FSK-mediated response. The level of CgB was also increased in FSK-treated cells, as evidenced by immunofluorescent analysis which showed a more intense staining in PC12 cells treated with FSK for 48 h than in untreated cells. The intensity of SgII staining was diminished by FSK treatment, most likely a result of a decreased rate of synthesis as well as an increase in the release of SgII. This study demonstrated that the mRNA and protein levels of CgB and SgII are differentially regulated by cAMP in PC12 cells.     

Life-threatening cat-scratch disease in an immunocompromised host

We describe a renal allograft recipient with cat-scratch disease in whom refractory hypotension, severe metabolic acidosis, pulmonary infiltrates, and encephalopathy developed. The patient first presented with a history of cat bites and scratches, fever, headache, and arthralgias. Four weeks later, the clinical presentation of septic shock suddenly developed in the patient. Cat-scratch disease was documented clinically and by finding delicate pleomorphic bacilli in Warthin-Starry silver stains of biopsy specimens taken from the primary inoculation site and regional lymph node. The administration of intravenous sulfamethoxazole and trimethoprim, erythromycin lactobionate, and tobramycin sulfate therapy correlated with recovery. Although cat-scratch disease is usually a benign, self-limited illness, this article illustrates its systemic nature, its potential for devastating complications in the immunocompromised host, and its possible response to vigorous antibiotic therapy.