Citations

Purpose Currently, there is little information available concerning the results of shoulder synovectomy in patients with rheumatoid arthritis. Furthermore, it remains difficult to assess the success of shoulder synovectomy because of a high association of rotator cuff tears in rheumatoid patients. We hypothesized that synovectomy in patients with a functionally intact rotator cuff would provide durable pain relief. Type of Study Case series. Methods Sixteen shoulders in 13 patients with rheumatoid arthritis were treated with arthroscopic shoulder synovectomy from 1988 to 2002 with a mean follow‐up of 5.5 years. Patients with full‐thickness rotator cuff tears or partial tears that required repair were excluded. Two of the 13 patients had been diagnosed with juvenile rheumatoid arthritis and 11 had adult‐onset disease. The medical records of the patients were reviewed and patients were assessed clinically and by questionnaire to assess pain, satisfaction, range of motion, radiographic outcomes, and occurrence of complications. Results There was an improvement in pain at long‐term follow‐up in 13 of 16 patients ( P < .001). Active shoulder elevation improved from a median of 145° to 160° but was not significant ( P = .14). External rotation improved significantly ( P = .01) from a median of 45° (range, 0° to 90°) to 60° (range, 0° to 100°). According to the Neer rating system, there were 5 excellent, 8 satisfactory, and 3 unsatisfactory results. Seven of 8 shoulders followed‐up radiographically for more than 1 year showed radiographic progression of disease. All 3 patients reporting pain that was no better or worse than before surgery had radiographic arthrosis at last follow‐up with advancing periarticular erosions and reduction of glenoid articular space. Conclusions Arthroscopic synovectomy of the shoulder in patients with rheumatoid arthritis with an intact rotator cuff offers a reliable decrease in pain with less predictable improvements in range of motion. Limitations in predicting final results based on preoperative radiographs should be discussed with patients; those with more advanced radiographic changes may not benefit from the procedure. Level of Evidence Level IV, therapeutic study, case series, no control group.

The mechanisms underlying aneuploidy in multiple myeloma (MM) are unclear. Centrosome amplification has been implicated as the cause of chromosomal instability in a variety of tumors and is a potential mechanism causing aneuploidy in MM. Using immunofluorescent (IF) staining, centrosome amplification was detected in 67% of monoclonal gammopathies, including monoclonal gammopathy of undetermined significance (MGUS). We also investigated the gene expression of centrosome proteins. Overall, gene expression data correlated well with IF-detected centrosome amplification, allowing us to derive a gene expression-based centrosome index (CI) as a surrogate for centrosome amplification. Clinically, MM patients with high CI (> 4) are associated with poor prognostic genetic and clinical subtypes (chromosome 13 deletion, t(4; 14), t(14;16), and PCLI > 1%, P < .05) and are shown here to have short survival (11.1 months versus 39.1 months, P < .001). On multivariate regression, a high CI is an independent prognostic factor. Given that centrosome amplification is already observed in MGUS and probably integral to early chromosomal instability and myeloma genesis, and patients with more extensive centrosome amplification have shorter survival, the mechanisms leading to centrosome amplification should be investigated because these may offer new avenues for therapeutic intervention.

BackgroundBiomarkers that have been developed largely for the study of patients with clinically diagnosed Alzheimer's disease (AD) can also be used in the study of cognitively normal individuals who may harbor underlying AD pathology.MethodsA meeting of invited experts on AD biomarkers was held on November 11 and 12, 2004 to review currently available data and to discuss unmet needs for biomarker research in presymptomatic AD.ResultsNeuroimaging biomarkers have been studied to some extent in subjects at risk for AD. These imaging techniques include volumetric magnetic resonance imaging and positron emission tomography using either fluorodeoxyglucose or newer ligands that bind directly to amyloid plaque. Similarly, biochemical measures from cerebrospinal fluid or other physiologic fluids are emerging as potentially useful tools. Such biomarkers may be used either as diagnostic tools or as indicators of disease severity when followed longitudinally. A clinical diagnosis of asymptomatic individuals using biomarkers and studies involving asymptomatic subjects may raise logistical and ethical concerns.ConclusionsThe technical development of biomarkers that are used for presymptomatic AD diagnosis and for longitudinally measuring disease severity is evolving rapidly. Ethical and privacy considerations must be made before such biomarkers can be applied routinely to asymptomatic populations.

ABSTRACT The Ref1 and Lv1 postentry restrictions in human and monkey cells have been analyzed for lentiviruses in the primate and ungulate groups, but no data exist for the third (feline) group. We compared feline immunodeficiency virus (FIV) to other restricted (human immunodeficiency virus type 1 [HIV-1], equine infectious anemia virus [EIAV]) and unrestricted (NB-tropic murine leukemia virus [NB-MLV]) retroviruses across wide ranges of viral inputs in cells from multiple primate and nonprimate species. We also characterized restrictions conferred to permissive feline and canine cells engineered to express rhesus and human TRIM5α proteins and performed RNA interference (RNAi) against endogenous TRIM5α. We find that expression of rhesus or human TRIM5α proteins in feline cells restricts FIV, impairing pseudotyped vector transduction and viral replication, but rhesus TRIM5α is more restricting than human TRIM5α. Notably, however, canine cells did not support restriction by human TRIM5α and supported minimal restriction by rhesus TRIM5α, suggesting that these proteins may not function autonomously or that a canine factor interferes. Stable RNAi knockdown of endogenous rhesus TRIM5α resulted in marked increases in FIV and HIV-1 infectivities while having no effect on NB-MLV. A panel of nonprimate cell lines varied widely in susceptibility to lentiviral vector transduction, but normalized FIV and HIV-1 vectors varied concordantly. In contrast, in human and monkey cells, relative restriction of FIV compared to HIV-1 varied from none to substantial, with the greatest relative infectivity deficit for FIV vectors observed in human T-cell lines. Endogenous and introduced TRIM5α restrictions of FIV could be titrated by coinfections with FIV, HIV-1, or EIAV virus-like particles. Arsenic trioxide had complex and TRIM5α-independent enhancing effects on lentiviral but not NB-MLV infection. Implications for human gene therapy are discussed.

C-terminal brain (B-type) natriuretic peptide (BNP)-32 is a widely used clinical biomarker for the diagnosis, prognosis, and treatment of heart failure (HF). The 32-aa peptide is synthesized primarily in the atrial and ventricular myocardium and constitutes the mature biologically active form of immature BNP (pro-BNP). There has been mounting evidence that suggests BNP circulates in different structural forms that impact HF diagnosis and in vivo activity. Herein, we have developed and used an immunoaffinity purification assay to isolate endogenous BNP-32 from New York Heart Association class IV patient plasma for subsequent analysis by nano-liquid chromatography (LC) electrospray ionization Fourier transform ion cyclotron resonance (FT-ICR) MS. We have introduced stable isotope-labeled BNP-32 to the assayed plasma to enable quantification of endogenous levels of BNP-32. Unlike the chemically nonspecific point-of-care tests (POCTs) and RIAs used worldwide to quantify BNP-32 from plasma, FT-ICR-MS (unprecedented mass measurement accuracy) coupled with LC (retention time) affords extraordinary molecular specificity, and when combined with the use of internal standards is able to confidently identify and quantify BNP-32. The significance of this work is despite exceedingly high circulating levels of BNP-32 in the New York Heart Association class IV patients as determined by POCTs (>290 fmol/ml) nano-LC-electrospray ionization-FT-ICR-MS data did not reveal any endogenous BNP-32. These results provide molecularly specific evidence for the absence of circulating BNP-32 in advanced-stage HF patients and suggest the existence of altered forms of BNP that are contributing to the POCT values.