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Comparison of receiver operating characteristic curves on the basis of optimal operating points.

RATIONALE AND OBJECTIVES: We developed a method of comparing receiver operating characteristic (ROC) curves on the basis of the utilities associated with their optimal operating points (OOPs). METHODS: OOPs were computed for paired ROC curves on the basis of isocost lines in ROC space with slopes ranging from 0.1 to 3.0. For each pair of OOPs corresponding to a single isocost slope, the difference in costs and the variance of this difference was computed. A sensitivity analysis was thus obtained for the difference between the two curves over a range of isocost slopes. Three published data sets were evaluated using this technique, as well as by comparisons of areas under the curves and of true-positive fractions at fixed false-positive fractions. RESULTS: The OOPs of paired ROC curves often occur at different false-positive fractions. Comparisons of ROC curves on the basis of OOPs may provide results that differ from comparisons of curves at a fixed false-positive fraction. CONCLUSION: ROC curves may be compared on the basis of utilities associated with their OOPs. This comparison of the optimal performance of two diagnostic tests may differ from conventional statistical comparisons.

Costs and Cost Analysis↗

The pathological distinction between "deep penetrating" dermatofibroma and dermatofibrosarcoma protuberans.

In selected cases, the clinicopathological distinction between deep penetrating dermatofibroma (DPDF), which involves the subcutis, and dermatofibrosarcoma protuberans (DFSPs) may be challenging. In most instances, attention to the cytological constituency of the lesions and the overall architecture is sufficient to make this separation. DPDF is typified by cellular heterogeneity, including giant cells and lipidized histiocytes; when it extends into the hypodermis, it does so either using the interlobular subcuticular fibrous septa as scaffolds or in the form of broad pushing fronts of tumor. In contrast, DFSP is a cytologically monotypical tumor, which entraps subcutaneous adipocytes diffusely or grows in stratified horizontal plates in the hypodermis. In the minority of cases where conventional morphological analysis of optimal biopsy specimens is diagnostically indeterminate, immunostaining for CD34 and factor XIIIa (FXIIIa) is helpful; it is also often necessary when a poorly-representative sample of the lesion has been obtained by the clinician. Characteristically, DF is diffusely FXIIIa-reactive and CD34-negative, whereas DFSP manifests the converse of those findings. Other markers such as Ki-M1p, mutant p53 protein, and metallothionein may also provide adjuvant diagnostic information in this context, as may the observation of abnormalities in chromosomes 17 and 22 by direct karyotypic analysis.

Dermatofibrosarcoma↗

Hydroxypropyl cellulose as an adsorptive coating sieving matrix for DNA separations: artificial neural network optimization for microchip analysis.

Effective DNA separations in microelectrophoretic systems are complicated by the need to passivate the surface dynamically or covalently. We describe the optimization and utilization of a novel buffer system for fast DNA separations by capillary and microchip electrophoresis without the need for any surface modification or conditioning prior to separation. At concentrations as high as 5%, hydroxypropyl cellulose (HPC) has a relatively low viscosity, allowing for microchip channel filling to be performed with ease. A MES/TRIS buffer system at pH 6.1 eliminates the need for surface preconditioning procedures due to the promotion of hydrogen bonding of HPC with the wall. An additional benefit with this buffer system is the low current observed at high fields when compared to other common DNA separation buffers. An artificial neural network (ANN) was used to model the data and to predict the optimum conditions. Utility of the ANN-optimized system for molecular diagnostic testing was demonstrated by performing microchip separations on DNA samples from patients suspected of having genetic mutations associated with Duchenne muscular dystrophy (DMD). Microchip analysis easily allowed for the patient samples positive for DMD mutations to be distinguished from patient samples negative for the disease.

Adsorption↗

Methods of estimation of visceral fat: advantages of ultrasonography.

OBJECTIVE: To compare methods for the assessment of visceral fat with computed tomography (CT) and establish cutoffs to define visceral obesity based on such alternative methods. RESEARCH METHODS AND PROCEDURES: One hundred women (50.4 +/- 7.7 years; BMI 39.2 +/- 5.4 kg/m2 underwent anthropometric evaluation, bioelectrical impedance, DXA, abdominal ultrasonography (US), and CT scan. RESULTS: Waist circumference, waist-to-hip ratio (WHR), and US-determined visceral fat values showed the best correlation coefficients with visceral fat determined by CT (r = 0.55, 0.54, and 0.71, respectively; p < 0.01). Fat mass determined by DXA was inversely correlated with visceral-to-subcutaneous-fat ratio (r = -0.47, p < 0.01). Bioimpedance-determined fat mass and skinfolds were correlated with only subcutaneous abdominal fat quantified by CT. Linear regression indicated US visceral-fat distance and WHR as the main predictors of CT-determined visceral fat (adjusted r2 = 0.51, p < 0.01). A waist measurement of 107 cm (82.7% specificity, 60.6% sensitivity) and WHR of 0.97 (78.8% specificity, 63.8% sensitivity) were chosen as discriminator values corresponding with visceral obesity diagnosed by CT. A value of 6.90 cm for visceral fat US-determined diagnosed visceral obesity with a specificity of 82.8%, a sensitivity of 69.2%, and a diagnostic concordance of 74% with CT. DISCUSSION: US seemed to be the best alternative method for the assessment of intra-abdominal fat in obese women. Its diagnostic value could be optimized by an anthropometric measurement. Prospective studies are needed to establish CT and US cutoffs for defining visceral-fat levels related to elevated cardiovascular risk.

Abdomen↗

AHNP-streptavidin: a tetrameric bacterially produced antibody surrogate fusion protein against p185her2/neu.

The anti-p185(her2/neu) peptidomimetic (AHNP) is a small exo-cyclic peptide derived from the anti-p185(her2/neu) rhumAb 4D5 (h4D5). AHNP mimics many but not all of the antitumor characteristics exhibited by h4D5. However, the pharmacokinetic profiles of AHNP are less than optimal for therapeutic or diagnostic purposes. To improve the binding affinity to p185(her2/neu) and the antitumor efficacy, we have engineered a fusion protein containing AHNP and a nonimmunoglobulin protein scaffold, streptavidin (SA). The recombinant protein, AHNP-SA (ASA) bound to p185(her2/neu) with high affinity, inhibited the proliferation of p185(her2/neu)-overexpressing cells, and reduced tumor growth induced by p185(her2/neu)-transformed cells. These data suggest that the bacterially produced tetrameric ASA can be used as an antibody-surrogate molecule. This class of molecule will play a role in the diagnosis and treatment of p185(her2/neu)-related tumors. Our studies establish a general principle by which a small biologically active synthetic exo-cyclic peptide can be engineered to enhance functional aspects by structured oligomerization and can be produced recombinantly using bacterial expression.

Animals↗

Echocardiography: common pitfalls and practical solutions.

The asymmetric shape of the heart, small acoustic window, and range of interindividual variation in normal and abnormal states all can limit the extent of echocardiographic studies in small animal medicine. Beyond these uncontrollable variables, however, there are a number of additional potentially complicating factors that the echocardiogapher controls. Understanding and handling this second category of variables is critical for optimizing the quality and diagnostic value of echocardiographic studies. These variables range from such simple issues as proper restraint and an indissociable association between echocardiographic findings and clinical information, to specific points relating to simultaneous electrocardiogram display, good visualization of cardiac structures using multiple overlapping imaging planes, and avoidance of oblique or tangential views. The basic overview presented here aims to describe these commonly encountered, clinically relevant points in a way that helps veterinarians improve the quality of echocardiograms they perform.

Animals↗

Basics of intravascular ultrasound: an essential tool for the endovascular surgeon.

The concept of catheter-based ultrasound imaging was first introduced in the early 1970s. Since its inception, intravascular ultrasound (IVUS) technology has become more user-friendly because of improvements in both the catheters and computer-driven imaging platforms. IVUS catheters enable luminal and transmural cross-sectional imaging of coronary and peripheral blood vessels with high-dimensional accuracy and detailed information about lesion morphology. With the advent of endovascular techniques in both the coronary and peripheral vasculature, IVUS has emerged as a useful and necessary adjunct. In addition to providing diagnostic information, IVUS enables optimal choice of appropriate angioplasty technique, endovascular device guidance, and controlled assessment of the efficacy of interventions. In this review we discuss the design and function of available IVUS catheters, imaging techniques and interpretation, and the present and future clinical utility in peripheral endovascular interventions.

Forecasting↗

[Non-occlusive mesenteric ischemia].

The so-called non-occlusive disease (NOD) or non-occlusive mesenteric ischemia (NOMI) is a severe and life-threatening pathology. Even under optimal circumstances and standardised diagnostic and therapeutic procedures maximum survival rates do not exceed 50 %. The NOD is a pathology of the elder patient and its incidence rises with other comorbidities such as reduced cardiac output, diabetes and renal insufficiency. Induction of the disease with a severe vasoconstriction of the splanchnic vessels may be a simple cardiac decompensation, a frequent trigger however is a previous heart surgery with consecutive cardiac shock. Early diagnosis is difficult to conduct because of unspecific symptoms. Beside abdominal pain in awake patients, ileus or subileus is remaining the single acute symptom which could be also a consequence of a postoperative paralysis. Laboratory parameters such as leucocytosis and elevated lactat levels are often positive, but unspecific and the latter may be a delayed sign of progressive disease. The only sufficient method for diagnosis implicating a possible treatment option seems to be an immediate angiographic examination. Because of the disappointing results of a solitary surgical approach transarterial medication via catheter is indicated. Depending of the course of the disease only a combination of local mesenteric infusion of vasodilatory drugs and surgical resection of already necrotic bowel promises a successful therapeutic approach and better survival rates.

Abdominal Pain↗

[The diagnostic value of pharmacoangiography in tumourous and inflammatory diseases of bones and soft tissues (author's transl)].

The value of pharmaco-angiography (Priscol, angiotensin) in the diagnosis of tumourous and inflammatory diseases in bones and soft tissues was investigated in 81 patients. Priscol was used in 49 patients, angiotensin in 28 and both substances in four. It was shown that neither Priscol nor angiotensin produced results of diagnostic value, provided an optimal technique was used (antegrade, selective contrast injection with an adequate volume of contrast and in the absence of vascular spasm). Priscol was of value for reducing or preventing spasm in peripheral vessels. Angiotensin is superior to Priscol in demonstrating the angiographic criteria, but pharmaco-angiography did not result in a better distinction between tumours and inflammatory lesions.

Adolescent↗

Evaluation of sperm damage and techniques for sperm clean-up.

The cryopreservation of bull semen adversely affects the metabolism, motility and membrane integrity of the spermatozoa, thereby decreasing the fertilizing ability of the processed sample. The present review covers methods available for examining the functionality of bull spermatozoa after thawing, including the use of fluorophores in combination with morphological examination. Procedures for clean-up, separation and selection of morphologically-normal, viable spermatozoa in vitro are also reviewed. Among the reviewed procedures are methods for dilution and washing and the selective fractionation of sperm subpopulations (especially density-gradient centrifugation in silica-bead suspensions), as well as methods based on adherence to glass (differential filtration) and sperm self-migration (particularly swim-up through hyaluronic acid). Emphasis is placed on assessing the value of these techniques for diagnostic purposes and for optimizing the methodology of in vitro fertilization.

Acrosome↗

The performance and utility of rapid diagnostic assays for Plasmodium falciparum malaria in a field setting in the Lao People's Democratic Republic.

Rapid diagnostic assays for malaria have the potential to improve the management and control of the disease in developing countries. The objectives of the present study were to evaluate, in a field setting, the performance of several such assays for Plasmodium falciparum infection and to examine the usefulness of these assays in identifying subjects for treatment trials in rural field sites. Residents of 12 villages in Laos who presented with fever were eligible for inclusion. Blood was collected by fingerprick for a dipstick assay, developed by the Program for Appropriate Technology in Health (PATH), performed and interpreted in the field by local healthcare workers. Compared with 'blinded' reference microscopy (N =196), the sensitivity and specificity of the PATH assay were 96.2% and 93.0%, respectively. Two rapid diagnostic assays (PATH and OptiMAL) were also performed on the subset of subjects eligible to participate in an in-vivo treatment trial (N = 97), and the results again compared with those of 'blinded' reference microscopy. In this subset, a subject was considered a 'true positive' if found positive by microscopy or the alternate rapid assay. Using this modified reference standard, the sensitivity and specificity of the PATH assay were 96.7% and 94.4%, and those of the OptiMAL assay were 91.8% and 100%, respectively. Both of the rapid assays tested therefore appear suitable for use in rural field settings by local healthcare providers and can accurately identify participants for treatment trials.

Developing Countries↗

Value of early blood Th-1 cytokine determination in predicting severity of acute pancreatitis.

BACKGROUND: Early evaluation of the severity of acute pancreatitis (AP) requires measurement of many variables within 48 h after admission. Septic complications (SC) are frequent, and preliminary studies have highlighted the value of prophylactic antibiotherapy; however, single and reliable predictive markers of sepsis are not yet available. The aim of this study was to assess the value of determining early blood Th-1 cytokines and their natural antagonists (interleukin-6 (IL-6), IL-1, IL-1ra, and the soluble form of tumor necrosis factor (sTNF) receptors RI and RII) to predict the severity and SC during AP. METHODS: Thirty-seven patients with AP were prospectively included; 25 of them had severe AP, including 8 with SC. Serum cytokines were measured 48 h and 72 h after the onset of AP with an enzyme-linked immunosorbent assay. The optimal severity or SC diagnostic thresholds was determined using receiver operative curves. RESULTS: Severe AP in accordance with the Atlanta criteria were better predicted by C-reactive protein and IL-6 serum determination, albeit these levels could not predict absolutely the death of two patients. In severe AP cases (n = 25) the IL-1 to IL-1-ra ratio was lower in cases further complicated by sepsis ((6+/-4) 10(-3) versus (34+/-13) 10(-3), P < 0.05); moreover, sTNF RI (2497+/-270 pg/ml versus 2133+/-611 pg/ml, P < 0.05) and RII (3751+/-400 pg/ml versus 3045+/-509 pg/ml, P < 0.05) were higher in AP characterized by further SC. The IL-1 to IL-1-ra ratio and IL-1 concentration were dramatically decreased within the first 48 h ((0.4+/-0.4) 10(-3) versus (30+/-11) 10(-3), P < 0.05, and 0.3+/-0.3 versus 15+/-3 ng/l, P < 0.05) in patients with further infection of the pancreatic necrosis (n = 3). The SC diagnosis was better anticipated by an IL-1 to IL-1-ra ratio lower than 5 x 10(-3) or by an sTNF RI higher than 1750 pg/ml and sTNF RII higher than 2750 pg/ml, and the infection of the pancreatic necrosis by an IL-1 concentration <2 ng/l or an IL-1 to IL-1-ra ratio <2 x 10(-3). CONCLUSION: Besides severity markers, IL-1, IL-1-ra, and sTNF RI and RII should be considered in base-line AP assays and, if confirmed by larger studies, could help to screen patients at risk for SC and candidates for prophylactic antibiotherapy with a good negative predictive value.

Acute Disease↗

IT-driven patient safety at the heart of radiology service improvement.

Patient safety is a fundamental requirement of modern health-care systems and the application of information technology (IT) to this activity should have improvements in the area as one of its goals. Indeed, ensuring that the diagnostic IT strategy is optimized, for example, the use of IT in service redesign or data analysis, forms one of the main platforms for the National Framework for Service Improvement in Radiology. This paper presents both the concept behind and the results of a project that has been under way in the UK involving St Helens and Knowsley NHS Trust and IRS Ltd concerned with implementing effective IT-driven scientific support in the field of medical radiation protection. Locally developed software is employed in assessing, managing, and analysing patient dose data arising from X-ray examinations performed in the busy department of a large district general hospital (DGH). Such data are analysed in a variety of ways, for example, over time and according to location (department or X-ray room). This analysis not only provides a measure of performance against nationally agreed dose reference levels (DRLs) but also enables a detailed analysis of any variations as well as the establishment of local DRLs (performance indicators). This process provides quantitative input to management strategies aimed at service improvement. Such strategies are geared towards the support of the Ionizing Radiations (Medical Exposures) Regulations 2000 as well as implementation of quality-management principles at the heart of radiology practices.

Cooperative Behavior↗

Phialemonium: an emerging mold pathogen that caused 4 cases of hemodialysis-associated endovascular infection.

Phialemonium species are emerging as fungal opportunistic pathogens of humans; infections caused by these fungi often have a fatal outcome. We report a series of 4 patients undergoing chronic hemodialysis who developed intravascular infection with Phialemonium curvatum. All isolates were of a distinct morphological type but were shown by partial ribosomal sequencing to be closely related to reference isolates of P. curvatum. Two patients in our case series died; both developed overwhelming infection associated with fungemia and endocarditis. Recent literature corroborates our experience that Phialemonium infection presents unique diagnostic challenges and that optimal management, particularly with regard to antifungal therapy, is not known.

Adult↗

Experimental energy response verification of XR type T radiochromic film.

This short note investigates the energy response characteristics of a relatively new high sensitivity radiochromic film (XR type T) and compares it to other radiochromic and radiographic films and thermoluminescent dosimeters. Results show that the energy response of the new XR type T film is relatively large over the range of therapeutic energies from 50 kVp superficial x-ray treatment to 18 MV high energy radiotherapy treatment. When normalized to 1 at a standard 6 MV radiotherapy x-ray energy the XR type T film produced a normalized dose response of approximately 6 in the energy range of 30 keV to 70 keV thus representing an increase in sensitivity at lower energies similar to that observed for radiographic x-ray films. This is quite different from previous versions of Gafchromic film where the energy response of the film decreases at lower energies down to levels approximately 0.6-0.7 for the same effective energies. This type of film has been optimized for use in diagnostic energy ranges producing a relatively uniform dose response in the 30 keV to 70 keV range.

Dose-Response Relationship, Radiation↗

Helical CT findings in patients with hepatocellular carcinoma treated with percutaneous ablation procedures.

Nonsurgical treatment of hepatocellular carcinoma is used worldwide as a result of the early detection and slow growth of this tumor in patients with chronic liver disease. Multiple-phase helical computed tomography is a commonly used method for evaluating the main features related to percutaneous ablation procedures: nodular changes, tumor necrosis, parenchymal changes, complications, and tumor recurrence. Knowledge of all features recognizable after local ablation therapy is mandatory to avoid diagnostic pitfalls and to optimally assess treatment response.

Carcinoma, Hepatocellular↗

Fever of unknown origin, infection of subcutaneous devices, brain abscesses and endocarditis.

The term 'fever of unknown origin' includes a wide range of conditions that often remain undiagnosed. The possibility of an infection must be promptly diagnosed in order to begin appropriate therapy. Imaging with radiopharmaceuticals, computed tomography, magnetic resonance imaging and ultrasound are the most commonly applied techniques, usually performed in addition to blood tests, biopsies or tissue cultures when required. The lack of comparative studies investigating the accuracy of each radiopharmaceutical for the study of fever of unknown origin was the incentive to perform a meta-analysis of peer articles published between 1981 and 2004 (33 papers) describing the use of nuclear medicine imaging for this purpose. Furthermore, infection of subcutaneous devices, brain abscesses and endocarditis must be considered amongst the causes of fevers of unknown origin. Reviews of 23, 10 and 10 papers, respectively (from 1976 to 2005), were performed on these specific topics. The results may be a useful guide for the choice of the optimal radiopharmaceutical(s) and diagnostic strategy to be applied in each clinical condition and for different aims.

Algorithms↗

Contemporary issues in the management of pediatric infections.

BACKGROUND: Pediatric infections still pose numerous challenges, and expert guidance is needed on many current issues including diagnostic methods and the optimal choice and duration of therapy. OBJECTIVES: To highlight areas of current concern and controversy and to provide some pointers to factors affecting the choice of antibiotic therapy. DISCUSSION: Most community-acquired pediatric infections are diagnosed on clinical grounds. Treatment is initiated on an empiric basis; microbiologic diagnosis is usual only for urinary tract infections and tonsillitis. The choice of the most appropriate antibiotic agent for ambulatory treatment depends on antimicrobial activity and pharmacokinetic parameters as well as on compliance-enhancing features such as once daily dosing, good tolerability and the acceptability of the pediatric formulation. The newer oral cephalosporins such as ceftibuten have a favorable combination of properties including excellent clinical efficacy and are increasingly being used in preference to penicillins. Although clinical cure is regarded as the "gold standard" in the evaluation of therapy, the importance of bacterial eradication must also be emphasized.

Anti-Bacterial Agents↗