Exclusion of first-episode deep-vein thrombosis after-hours using D-dimer.

The objective of this study was to test the safety of withholding anticoagulant treatment and additional call-back diagnostic testing with ultrasound in patients who have a negative D-dimer at presentation. Patients with signs and symptoms of deep-vein thrombosis who presented to the emergency department after regular hours and on weekends underwent D-dimer testing using the STA-Liatest D-di. In patients with negative D-dimer results, heparin therapy was withheld, and no further diagnostic testing for deep-vein thrombosis was done as part of the initial evaluation. Patients with positive D-dimer results underwent compression ultrasonography. The primary outcome measure was a diagnosis of new symptomatic venous thromboembolism confirmed by diagnostic testing during the 3-month follow-up period. Of the 260 eligible patients, 81 (31%) had a negative D-dimer and 179 (69%) had a positive D-dimer. No patient with a negative D-dimer at presentation had confirmed venous thromboembolism at 3-month follow-up. Three patients died: one by intracranial hemorrhage secondary to cerebrovascular accident; and two deaths of indeterminate cause almost 3 months after entry. The automated assay for D-dimer, the STA-Liatest D-di, seems to provide a simple method with high clinical utility for excluding acute first-episode deep-vein thrombosis in symptomatic patients who present to the emergency room after regular hours.     

Comparison of risk stratification with pharmacologic and exercise stress myocardial perfusion imaging: A meta-analysis

BACKGROUND: Although pharmacologic stress myocardial perfusion imaging (MPI) and exercise stress MPI have comparable diagnostic accuracy, their comparative value for risk stratification of patients with known or suspected coronary disease is not known. METHODS AND RESULTS: The data of 14,918 patients were combined from 24 studies evaluating prognosis in patients undergoing either pharmacologic stress or exercise stress MPI. Studies were included if a 2 x 2 table for hard cardiac events (cardiac death and myocardial infarction [MI]) could be constructed from the data available. Excluded were studies performed for post-MI, post-revascularization, or preoperative risk stratification. A weighted t test was used to compare the cardiac events, and a random effects model was used to calculate summary odds ratios. Summary odds ratios for hard cardiac events were similar for pharmacologic stress and exercise stress MPI. Summary receiver operating characteristic curves also showed no difference in discriminatory power between the stressors. The cardiac event rates were significantly higher with normal and abnormal test results with pharmacologic stress MPI than with exercise stress MPI (1.78% vs 0.65% [P < .001] for normal results and 9.98% vs 4.3% [P < .001] for abnormal results). Subgroup analysis revealed that both cardiac death and nonfatal MI were significantly higher with pharmacologic stress MPI. Patients undergoing pharmacologic stress MPI had a significantly higher prevalence of poor prognostic factors, and meta-regression revealed that exercise capacity was the single most important predictor of cardiac events. CONCLUSIONS: This meta-analysis shows that exercise stress MPI and pharmacologic stress MPI are comparable in their ability to risk-stratify patients. However, patients undergoing pharmacologic stress studies are at a higher risk for subsequent cardiac events. This is true even for those with normal perfusion imaging results.     

Users' subjective evaluation of electronic vision enhancement systems

The aims of this study were (1) to elicit the users' responses to four electronic head-mounted devices (Jordy, Flipperport, Maxport and NuVision) and (2) to correlate users' opinion with performance. Ten patients with early onset macular disease (EOMD) and 10 with age-related macular disease (AMD) used these electronic vision enhancement systems (EVESs) for a variety of visual tasks. A questionnaire designed in-house and a modified VF-14 were used to evaluate the responses. Following initial experience of the devices in the laboratory, every patient took home two of the four devices for 1 week each. Responses were re-evaluated after this period of home loan. No single EVES stood out as the strong preference for all aspects evaluated. In the laboratory-based appraisal, Flipperport typically received the best overall ratings and highest score for image quality and ability to magnify, but after home loan there was no significant difference between devices. Comfort of device, although important, was not predictive of rating once magnification had been taken into account. For actual performance, a threshold effect was seen whereby ratings increased as reading speed improved up to 60 words per minute. Newly diagnosed patients responded most positively to EVESs, but otherwise users' opinion could not be predicted by age, gender, diagnosis or previous CCTV experience. User feedback is essential in our quest to understand the benefits and shortcoming of EVESs. Such information should help guide both prescribing and future development of low vision devices.     

Comparing diffusion-weighted and T2-weighted MR imaging for the quantification of infarct size in a neonatal rat hypoxic–ischemic model at 24 h post-injury

PURPOSE: In a neonatal rat model of hypoxic-ischemic (HI) brain injury, using T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), we aim to determine the best MRI method of lesion quantification that reflects infarct size. MATERIALS AND METHODS: Twenty 7-day-old rats underwent MRI 24h after HI brain injury was induced. Lesion size relative to whole brain was measured using T2WI and apparent diffusion coefficient (ADC) maps, applying thresholds of 60%, 70% and 80% contralateral control hemisphere mean ADC, and at day 10 post-HI on pathology with TTC staining. Multiple linear regression analysis was used to study the relationships between lesion size at MRI and pathology. RESULTS: Lesion size measurement using all MRI methods significantly correlated with infarct size at pathology; using T2WI, r=0.808 (p<0.001), using 80% ADC, 70% ADC and 60% ADC thresholds, r=0.888 (p<0.001), 0.761, (p<0.001) and 0.569 (p=0.014), respectively. Eighty percent ADC threshold was found to be the only significant independent predictor of final infarct volume (adjusted R(2)=0.775). CONCLUSION: At 24h post-HI, lesion size on DWI, using 80% ADC threshold is the best predictor of final infarct volume. Although T2WI performed less well, it has the advantage of superior spatial resolution and is technically less demanding. These are important considerations for experiments which utilize MRI as a surrogate method for lesion quantification in the neonatal rat HI model.     

3He MRI in mouse models of asthma.

In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available methods is insensitive because these techniques lack regional specificity. A more sensitive method for evaluating lung function in human asthma patients uses hyperpolarized (HP) (3)He MRI before and after bronchoconstriction induced by methacholine (MCh). We now report the ability to perform such (3)He imaging of MCh response in mice, where voxels must be approximately 3000 times smaller than in humans and (3)He diffusion becomes an impediment to resolving the airways. We show three-dimensional (3D) images that reveal airway structure down to the fifth branching and visualize ventilation at a resolution of 125 x 125 x 1000 microm(3). Images of ovalbumin (OVA)-sensitized mice acquired after MCh show both airway closure and ventilation loss. To also observe the MCh response in naive mice, we developed a non-slice-selective 2D protocol with 187 x 187 microm(2) resolution that was fast enough to record the MCh response and recovery with 12-s temporal resolution. The extension of (3)He MRI to mouse models should make it a valuable translational tool in asthma research.     

Gallstones Containing Bacteria are Biofilms: Bacterial Slime Production and Ability to Form Pigment Solids Determines Infection Severity and Bacteremia

Objective Gallstone bacteria provide a reservoir for biliary infections. Slime production facilitates adherence, whereas β-glucuronidase and phospholipase generate colonization surface. These factors facilitate gallstone formation, but their influence on infection severity is unknown. Methods Two hundred ninety-two patients were studied. Gallstones, bile, and blood (as applicable) were cultured. Bacteria were tested for β-glucuronidase/phospholipase production and quantitative slime production. Infection severity was correlated with bacterial factors. Results Bacteria were present in 43% of cases, 13% with bacteremia. Severe infections correlated directly with β-glucuronidase/phospholipase (55% with vs 13% without, P < 0.0001), but inversely with slime production (55 vs 8%, slime <75 or >75, P = 0.008). Low slime production and β-glucuronidase/phospholipase production were additive: Severe infections were present in 76% with both, but 10% with either or none (P < 0.0001). β-Glucuronidase/phospholipase production facilitated bactibilia (86% with vs 62% without, P = 0.03). Slime production was 19 (±8) vs 50 (±10) for bacteria that did or did not cause bacteremia (P = 0.004). No bacteria with slime >75 demonstrated bacteremia. Conclusions Bacteria-laden gallstones are biofilms whose characteristics influence illness severity. Factors creating colonization surface (β-glucuronidase/phospholipase) facilitated bacteremia and severe infections; but abundant slime production, while facilitating colonization, inhibited detachment and cholangiovenous reflux. This shows how properties of the gallstone biofilm determine the severity of the associated illness. Presented at the annual meeting of the Society for Surgery of the Alimentary Tract, held May 20–24, 2006 in Los Angeles, California.     

Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma.

Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting.     

National trends in Staphylococcus aureus infection rates: impact on economic burden and mortality over a 6-year period (1998-2003).

BACKGROUND: We evaluated historical trends in the Staphylococcus aureus infection rate, economic burden, and mortality in US hospitals from 1998 through 2003. METHODS: The Nationwide Inpatient Sample was used to assess trends over time of S. aureus infection during 1998-2003. Historical trends were determined for 5 strata of hospital stays, including all inpatient stays, surgical procedure stays, invasive cardiovascular surgical stays, invasive orthopedic surgical stays, and invasive neurosurgical stays. RESULTS: During the 6-year study period from 1998 through 2003, the rate of S. aureus infection increased significantly for all inpatient stays (from 0.74% to 1.0%; annual percentage change (APC), 7.1%; P=.004), surgical stays (from 0.90% to 1.3%; APC, 7.9%; P=.001), and invasive orthopedic surgical stays (from 1.2% to 1.8%; APC, 9.3%; P<.001). For invasive neurosurgical stays, the rate of S. aureus infection did not change from 1998 to 2000 but increased at an annual rate of 11.0% from 2000 to 2003 (from 1.4% to 1.8%; P=.034). The total economic burden of S. aureus infection for hospitals also increased significantly for all stay types, with the annual percentage increase ranging from 9.2% to 17.9% (P<.05 for all). In 2003, the total economic burden of S. aureus infection was estimated to be $14.5 billion for all inpatient stays and $12.3 billion for surgical patient stays. However, there were significant decreases in the risk of S. aureus-related in-hospital mortality from 1998 to 2003 for all inpatient stays (from 7.1% to 5.6%; APC, -4.6%; P=.001) and for surgical stays (from 7.1% to 5.5%; APC, -4.6%; P=.002). CONCLUSIONS: The inpatient S. aureus infection rate and economic burden of S. aureus infections for US hospitals increased substantially from 1998 to 2003, whereas the in-hospital mortality rate decreased.