Citations

ABSTRACT The COBAS AmpliPrep/COBAS AMPLICOR HIV-1 MONITOR Test, version 1.5 (CAP/CA), and the COBAS AMPLICOR HIV-1 MONITOR Test, version 1.5, were compared. CAP/CA reduced and consolidated labor while modestly increasing assay throughput without increased failure rates or direct costs, regardless of batch size and assay format.

Abstract The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed.

The purpose of this study was to establish a data base on the isokinetic eccentric muscular performance char acteristics of external and internal rotator muscles in the shoulders of professional baseball pitchers. Con centric data are also included and compared with pre viously published concentric studies. Twenty-five pro fessional baseball pitchers were evaluated with a Kin- Com isokinetic dynamometer. The subjects tested had a mean age of 23.5 years and a mean body weight of 199 pounds. Eccentric and concentric isokinetic tests were performed at 60 and 120 deg/sec. The testing protocol was standardized for each subject. Test re sults indicated no statistically significant difference in mean torque between throwing and nonthrowing shoulders for either external or internal rotator muscle groups. Eccentric strength was significantly greater than concentric strength for all muscle groups tested. The external-to-internal rotator muscle strength ratios were well above those previously published for high school through professional pitchers. Mean torque-to- lean body weight ratios were also included to establish a data base. This study establishes one of the first data bases for eccentric isokinetic muscle strength of shoul der rotator muscles in professional baseball pitchers. The data may help clinicians prevent and rehabilitate shoulder injuries in professional throwing athletes.

The stabilizing capacity of the ligaments and articular surface in the ankle was determined under defined physiologic loading conditions. The concept of primary and secondary constraints was adapted to the ankle. With physiologic loading, the articular surface ac counted for 30% and 100% of stability in rotation and version, respectively. That the articular surface was the sole source of inversion and eversion stability under the prescribed physiologic loading conditions has not been previously reported. The demonstration that the articular surface resists inversion displacement in the loaded ankle supports the conclusion of previous studies that rotation, rather than inversion, may account for a type of clinically sympto matic ankle instability. Further, ankle instability may occur during loading and unloading but not once the ankle is fully loaded. The results of our study confirm the importance of the anterior talofibular and calcaneo fibular ligaments and suggest an important role for the deltoid ligament.

Purpose Atypical hyperplasia is a well-recognized risk factor for breast cancer, conveying an approximately four-fold increased risk. Data regarding long-term absolute risk and factors for risk stratification are needed. Patients and Methods Women with atypical hyperplasia in the Mayo Benign Breast Disease Cohort were identified through pathology review. Subsequent breast cancers were identified via medical records and a questionnaire. Relative risks (RRs) were estimated using standardized incidence ratios, comparing the observed number of breast cancers with those expected based on Iowa Surveillance, Epidemiology, and End Results (SEER) data. Age, histologic factors, and family history were evaluated as risk modifiers. Plots of cumulative breast cancer incidence provided estimates of risk over time. Results With mean follow-up of 13.7 years, 66 breast cancers (19.9%) occurred among 331 women with atypia. RR of breast cancer with atypia was 3.88 (95% CI, 3.00 to 4.94). Marked elevations in risk were seen with multifocal atypia (eg, three or more foci with calcifications [RR, 10.35; 95% CI, 6.13 to 16.4]). RR was higher for younger women (< 45; RR, 6.76; 95% CI, 3.24 to 12.4). Risk was similar for atypical ductal and atypical lobular hyperplasia, and family history added no significant risk. Breast cancer risk remained elevated over 20 years, and the cumulative incidence approached 35% at 30 years. Conclusion Among women with atypical hyperplasia, multiple foci of atypia and the presence of histologic calcifications may indicate “very high risk” status (> 50% risk at 20 years). A positive family history does not further increase risk in women with atypia.

Background: Reliable measurement of subfascial pressures represents an essential part of compartment syndrome management. To date, there is neither consensus on the number or location of foot compartments, nor a standardized protocol for needle placement. The purpose of this study was to devise a new system using 3-Tesla MRI that assesses the number and location of these compartments. Methods: To document the specific location of foot compartments, high resolution 3-Tesla MRI (General Electric, Milwaukee, WI) was coupled with a dedicated transmit-receive high signal-to-noise foot/ankle coil (IGC-Medical Advances, Milwaukee, WI). Individual compartments were highlighted and mapped to T1-weighted MRI. Three-dimensional image analysis allowed standardized needle placement recommendations. Results: Six feet from healthy volunteers were imaged. From these, ten compartments were described: (1) medial, (2) central superficial, (3) central deep (adductor), (4) lateral, (5–8) interossei, (9) calcaneal, and (10) skin. Optimal needle placement and depth were identified. Conclusions: The proposed system allowed us to assess the number and location of foot compartments. Computer image analysis enabled us to define exact points for needle insertion and depth of penetration for accurate pressure monitoring.

Abstract Bone structure, strength, and load-strength ratios contribute to forearm fracture risk independently of areal BMD. Introduction: Technological and conceptual advances provide new opportunities for evaluating the contributions of bone density, structure, and strength to the pathogenesis of distal forearm fractures. Materials and Methods: From an age-stratified random sample of Rochester, MN, women, we compared 18 with a distal forearm fracture (cases) to 18 age-matched women with no osteoporotic fracture (controls). High-resolution pQCT was used to assess volumetric BMD (vBMD), geometry, and microstructure at the ultradistal radius, the site of Colles' fractures. Failure loads in the radius were estimated from microfinite element (μFE) models derived from pQCT. Differences between case and control women were assessed, and the risk of fracture associated with each variable was estimated by logistic regression analysis. Results: Given similar heights, estimated loading in a fall on the outstretched arm was the same in cases and controls. However, women with forearm fractures had inferior vBMD, geometry, microstructure, and estimated bone strength. Relative risks for the strongest determinant of fracture in each of the five main variable categories were as follows: BMD (total vBMD: OR per SD change, 4.2; 95% CI, 1.4–12), geometry (cortical thickness: OR, 4.0; 95% CI, 1.4–11), microstructure (trabecular number: OR, 2.3; 95% CI, 1.02–5.1), and strength (axial rigidity: OR, 3.8; 95% CI, 1.4–10); the factor-of-risk (fall load/μFE failure load) was 24% greater (worse) in cases (OR, 3.0; 95% CI, 1.2–7.5). Areas under ROC curves ranged from 0.72 to 0.82 for these parameters. Conclusions: Bone geometry, microstructure, and strength contribute to forearm fractures, as does BMD, and these additional determinants of risk promise greater insights into fracture pathogenesis.

Emerging technologies have greatly expanded our ability to detect, characterize, and treat colorectal cancer. The Coalition of Cancer Cooperative Groups convened a multidisciplinary panel, the Scientific Leadership Council in GI cancer, to discuss and advise on the priorities and opportunities to advance current and future approaches into the clinical arena to impact most rapidly the morbidity and mortality from this disease. The Council's recommendations for research priorities are the result of engagement of community and academic oncologists, patient advocacy groups, and other stakeholders including the pharmaceutical industry and governmental agencies. We detail some key prospects for investigation in the areas of colon cancer detection, prevention, and surgical and medical management. Many are in early or definitive clinical trials, and a focus on rapid accrual is urged. The implementation of biology-directed laboratory investigations, both in association with ongoing clinical trials and as a separate developmental strategy for targeted therapies, is supported as the route to individualized therapy.

ABSTRACTClostridium difficiletoxins A and B (TcdA and TcdB) are the causative agents of antibiotic-associated pseudomembranous colitis. Mucosal mast cells play a crucial role in the inflammatory processes underlying this disease. We studied the direct effects of TcdA and TcdB on the human mast cell line HMC-1 with respect to degranulation, cytokine release, and the activation of proinflammatory signal pathways. TcdA and TcdB inactivate Rho GTPases, the master regulators of the actin cytoskeleton. The inactivation of Rho GTPases induced a reorganization of the actin cytoskeleton accompanied by morphological changes of cells. The TcdB-induced reorganization of the actin cytoskeleton in HMC-1 cells reduced the number of electron-dense mast cell-specific granules. Accordingly, TcdB induced the release of hexosaminidase, a marker for degranulation, in HMC-1 cells. The actin rearrangement was found to be responsible for degranulation since latrunculin B induced a comparable hexosaminidase release. In addition, TcdB as well as latrunculin B induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 and also resulted in a p38 MAPK-dependent increased formation of prostaglandins D2and E2. The autocrine stimulation of HMC-1 cells by prostaglandins partially contributed to the degranulation. Interestingly, TcdB-treated HMC-1 cells, but not latrunculin B-treated HMC-1 cells, showed a strong p38 MAPK-dependent increase in interleukin-8 release. Differences in the mast cell responses to TcdB and latrunculin B are probably due to the presence of functionally inactive Rho GTPases in toxin-treated cells. Thus, the HMC-1 cell line is a promising model for studying the direct effects ofC. difficiletoxins on mast cells independently of the tissue context.