Optical imaging is a modality that is cost-effective, rapid, easy to use, and can be readily applied to studying disease processes and biology in vivo. For this study, we used a green fluorescent protein (GFP)- and luciferase-expressing mouse tumor model to compare and contrast the quantitative and

Optical imaging is a modality that is cost-effective, rapid, easy to use, and can be readily applied to studying disease processes and biology in vivo. For this study, we used a green fluorescent protein (GFP)- and luciferase-expressing mouse tumor model to compare and contrast the quantitative and qualitative capabilities of a fluorescent reporter gene (GFP) and a bioluminescent reporter gene (luciferase). We describe the relationship between tumor volume, tumor mass, and bioluminescent/fluorescent intensity for both GFP and luciferase. Bioluminescent luciferase imaging was shown to be more sensitive than fluorescent GFP imaging. Luciferase-expressing tumors were detected as early as 1 day after tumor cell inoculation, whereas GFP-expressing tumors were not detected until 7 days later. Both bioluminescent and fluorescent intensity correlated significantly and linearly with tumor volume and tumor weight, as measured by caliper. Compared to bioluminescent imaging, fluorescent imaging does not require the injection of a substrate and may be appropriate for applications where sensitivity is not as critical. Knowing the relative strengths of each imaging modality will be important in guiding the decision to use fluorescence or bioluminescence.

Recently, there has been tremendous interest in developing techniques such as MRI, micro-CT, micro-PET, and SPECT to image function and processes in small animals. These technologies offer deep tissue penetration and high spatial resolution, but compared with noninvasive small animal optical imaging

Recently, there has been tremendous interest in developing techniques such as MRI, micro-CT, micro-PET, and SPECT to image function and processes in small animals. These technologies offer deep tissue penetration and high spatial resolution, but compared with noninvasive small animal optical imaging, these techniques are very costly and time consuming to implement. Optical imaging is cost-effective, rapid, easy to use, and can be readily applied to studying disease processes and biology in vivo. In vivo optical imaging is the result of a coalescence of technologies from chemistry, physics, and biology. The development of highly sensitive light detection systems has allowed biologists to use imaging in studying physiological processes. Over the last few decades, biochemists have also worked to isolate and further develop optical reporters such as GFP, luciferase, and cyanine dyes. This article reviews the common types of fluorescent and bioluminescent optical imaging, the typical system platforms and configurations, and the applications in the investigation of cancer biology.

OBJECTIVE: We describe the effects of tumor necrosis factor alpha (TNFalpha) on tumor microvasculature in a murine colon carcinoma model using serial dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). MATERIAL AND METHODS: Mice with subcutaneous murine colon carcinomas (MC-38) were im

OBJECTIVE: We describe the effects of tumor necrosis factor alpha (TNFalpha) on tumor microvasculature in a murine colon carcinoma model using serial dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). MATERIAL AND METHODS: Mice with subcutaneous murine colon carcinomas (MC-38) were imaged at 4.7 T after administration of 0.2 mmol/kg gadolinium-DTPA. Both treated and control mice (each group, n = 4), were scanned at baseline and 2, 4, 6, and 96 hours. A 2-compartment pharmacokinetic model generated parameters such as K, kep, and initial area under the gadolinium concentration curve (IAUC). RESULTS: The treatment group revealed significant differences in K at all time points after TNFalpha. kep and IAUC were significantly reduced at 2, 6, and 96 hours. The coefficient of variation in control animals ranged from 0.13 for IAUC to 0.30 for K. Mild histologic changes were observed at 2 to 6 hours, but considerable central necrosis with a vascular tumor rim was seen at 96 hours. CONCLUSION: DCE MRI can be used to detect early effects of TNFalpha. Serial DCE MRI is a promising tool in assessing the early effects of antivascular therapies.

OBJECTIVE: We evaluated the ability of pretreatment MRI and PET/CT to improve outcomes for patients with clinically staged International Federation of Gynecology and Obstetrics (FIGO) IB cervical cancer. MATERIALS AND METHODS: We developed a decision-analytic model to predict outcomes for a hypothet

OBJECTIVE: We evaluated the ability of pretreatment MRI and PET/CT to improve outcomes for patients with clinically staged International Federation of Gynecology and Obstetrics (FIGO) IB cervical cancer. MATERIALS AND METHODS: We developed a decision-analytic model to predict outcomes for a hypothetical patient cohort with FIGO IB cervical cancer who underwent pretreatment MRI, PET/CT, MRI and PET/CT, or no further imaging (direct pursuance of surgery). The model incorporated imaging performance, underlying parametrial extension and lymph node involvement, surgery and chemoradiation treatment options, and survival penalties from incorrect assessment of disease extent. Three outcomes were compared: 5-year overall survival, percentage of patients receiving correct primary therapy, and percentage of patients spared "trimodality therapy" (surgery followed by chemoradiation). Sensitivity analysis was performed to assess the effects of model uncertainty on outcomes. RESULTS: The preferred imaging strategy depended on the outcome studied. Five-year overall survival was comparable across strategies but was highest with the no-imaging strategy (92.37%) and with PET/CT (92.36%) and lowest with MRI (92.30%). Triage to correct primary therapy was highest with PET/CT (89.27%) and lowest with MRI (68.21%). Avoidance of trimodality therapy was highest with combined MRI and PET/CT (95.01%) and lowest with the no-imaging strategy (82.32%). Results were somewhat sensitive to imaging test performance characteristics but stable across most parameter ranges tested. CONCLUSION: Pretreatment imaging of FIGO IB cervical cancer patients can optimize triage to appropriate therapy. Although imaging does not appear to improve survival, PET/CT maximizes patient triage to correct therapy, and combined MRI and PET/CT spares the most patients unnecessary trimodality therapy.

Premenopausal women who present with acute pelvic pain frequently pose a diagnostic dilemma, exhibiting nonspecific signs and symptoms, the most common being nausea, vomiting, and leukocytosis. Diagnostic considerations encompass multiple organ systems, including obstetric, gynecologic, urologic, ga

Premenopausal women who present with acute pelvic pain frequently pose a diagnostic dilemma, exhibiting nonspecific signs and symptoms, the most common being nausea, vomiting, and leukocytosis. Diagnostic considerations encompass multiple organ systems, including obstetric, gynecologic, urologic, gastrointestinal, and vascular etiologies. The selection of imaging modality is determined by the clinically suspected differential diagnosis. Thus, a careful evaluation of such a patient should be performed and diagnostic considerations narrowed before a modality is chosen. Transvaginal and transabdominal pelvic sonography is the modality of choice when an obstetric or gynecologic abnormality is suspected, and computed tomography is more useful when gastrointestinal or genitourinary pathology is more likely. Magnetic resonance imaging, when available in the acute setting, is favored over computed tomography for assessing pregnant patients for nongynecologic etiologies because of the lack of ionizing radiation.

I have developed an interactive microcomputer simulation program for the design, comparison, and evaluation of alternative quality-control (QC) procedures. The program estimates the probabilities for rejection under different conditions of random and systematic error when these procedures are used a

I have developed an interactive microcomputer simulation program for the design, comparison, and evaluation of alternative quality-control (QC) procedures. The program estimates the probabilities for rejection under different conditions of random and systematic error when these procedures are used and plots their power function graphs. It also estimates the probabilities for detection of critical errors, the defect rate, and the test yield. To allow a flexible definition of the QC procedures, it includes an interpreter. Various characteristics of the analytical process and the QC procedure can be user-defined. The program extends the concepts of the probability for error detection and of the power function to describe the results of the introduction of error between runs and within a run. The usefulness of this approach is illustrated with some examples.

In general, one cannot use algebraic or enumerative methods to optimize a quality-control (QC) procedure for detecting the total allowable analytical error with a stated probability with the minimum probability for false rejection. Genetic algorithms (GAs) offer an alternative, as they do not requir

In general, one cannot use algebraic or enumerative methods to optimize a quality-control (QC) procedure for detecting the total allowable analytical error with a stated probability with the minimum probability for false rejection. Genetic algorithms (GAs) offer an alternative, as they do not require knowledge of the objective function to be optimized and can search through large parameter spaces quickly. To explore the application of GAs in statistical QC, I developed two interactive computer programs based on the deterministic crowding genetic algorithm. Given an analytical process, the program "Optimize" optimizes a user-defined QC procedure, whereas the program "Design" designs a novel optimized QC procedure. The programs search through the parameter space and find the optimal or near-optimal solution. The possible solutions of the optimization problem are evaluated with computer simulation.

INTRODUCTION: HELLP syndrome is a variant of pregnancy-induced hypertension that is associated with significant maternal and perinatal morbidity and mortality. The aim of our study was to investigate the neonatal complications associated to this syndrome. PATIENTS AND METHOD: A retrospective observa

INTRODUCTION: HELLP syndrome is a variant of pregnancy-induced hypertension that is associated with significant maternal and perinatal morbidity and mortality. The aim of our study was to investigate the neonatal complications associated to this syndrome. PATIENTS AND METHOD: A retrospective observational study was carried out on all newborns of mothers with HELLP syndrome in Virgen del Rocio hospital from 1995 to 2005. There were 120 newborns of 99 mothers with HELLP syndrome. Gestational age, birth weight, length, skull perimeter, number of hospital admissions and mortality were analyzed. The birth weight, length and skull perimeter were compared with a healthy population of the same gestational age using Lubchenco charts. The statistical relationships were determined between the mothers' platelet counts and the birth weight and perinatal mortality. RESULTS: A total of 80% of pregnancies were preterm delivery with a mean gestational age of 33 weeks. Mean birth weight was 1,834g, length 41cm and skull perimeter 29cm. A third of newborns had fetal growth restriction. 61% of newborns needed admitting to hospital due to prematurity and low birth weight. There were 24 perinatal deaths. We did not find any correlation between the number of platelets of the mother and birth weight or perinatal mortality. CONCLUSIONS: HELLP syndrome is an uncommon but potentially serious complication of pregnancy which is associated with an increased risk of adverse maternal and fetal outcome.

BACKGROUND: Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, int

BACKGROUND: Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS: A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. RESULTS: A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than of patients who received interferon alfa-2b plus ribavirin (56 percent vs. 44 percent, P<0.001) or peginterferon alfa-2a alone (56 percent vs. 29 percent, P<0.001). The proportions of patients with HCV genotype 1 who had sustained virologic responses were 46 percent, 36 percent, and 21 percent, respectively, for the three regimens. Among patients with HCV genotype 1 and high base-line levels of HCV RNA, the proportions of those with sustained virologic responses were 41 percent, 33 percent, and 13 percent, respectively. The overall safety profiles of the three treatment regimens were similar; the incidence of influenza-like symptoms and depression was lower in the groups receiving peginterferon alfa-2a than in the group receiving interferon alfa-2b plus ribavirin. CONCLUSIONS: In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone.

The American College of Cardiology and American Heart Association have issued a "focused update" of their 2004 guidelines for the management of ST-segment elevation myocardial infarction (STEMI). Several of the issues addressed involve new data and new recommendations on treatment decisions that may

The American College of Cardiology and American Heart Association have issued a "focused update" of their 2004 guidelines for the management of ST-segment elevation myocardial infarction (STEMI). Several of the issues addressed involve new data and new recommendations on treatment decisions that may be made in the emergency department. In this review, we present the new recommendations that are pertinent to emergency medicine practice and comment on their potential implementation into an evidence-based, multidisciplinary approach to the timely care of the STEMI patient.

STUDY OBJECTIVE: Emergency clinician-performed ultrasonography holds promise as a rapid and accurate method to diagnose and exclude deep venous thrombosis. However, the diagnostic accuracy of emergency clinician-performed ultrasonography performed by a heterogenous group of clinicians remains undefi

STUDY OBJECTIVE: Emergency clinician-performed ultrasonography holds promise as a rapid and accurate method to diagnose and exclude deep venous thrombosis. However, the diagnostic accuracy of emergency clinician-performed ultrasonography performed by a heterogenous group of clinicians remains undefined. METHODS: Prospective, single-center study conducted at an urban, academic emergency department (ED). Clinician participants included ED faculty, supervised residents, and midlevel providers who completed a training course for above-calf, 3-point-compression, venous ultrasonography. Patient participants had suspected leg deep venous thrombosis and greater than or equal to 1 predefined sign or symptom. Before any imaging, clinicians classified patients as low (<15%), moderate (15% to 40%), or high (>40%) pretest probability of deep venous thrombosis, followed by emergency clinician-performed ultrasonography. A whole-leg reference venous ultrasonography was then performed and interpreted separately in the radiology department. Patients were followed for 30 days. The criterion standard for deep venous thrombosis( ), required thrombosis of any leg vein on a reference ultrasonograph and clinical plan to treat. RESULTS: We enrolled 183 patients, and 27 (15%) had deep venous thrombosis( ). The sensitivity and specificity emergency clinician-performed ultrasonography was 70% (95% confidence interval [CI] 60% to 80%) and 89% (95% CI 83% to 94%), respectively, with overall diagnostic accuracy of 85% (95% CI 79% to 90%). The posterior probability of deep venous thrombosis( ) among the 88 low-risk patients with a negative emergency clinician-performed ultrasonographic result was 1 of 88, or 1.1% (95% CI 0% to 6%), and the posterior probability of deep venous thrombosis( ) among 14 high-risk patients with a positive emergency clinician-performed ultrasonographic result was 11 of 14, or 79% (95% CI 49% to 95%). CONCLUSION: The overall diagnostic accuracy of single-visit emergency clinician-performed ultrasonography performed by a heterogeneous group of ED clinicians is intermediate but may be improved by pretest probability assessment.

STUDY OBJECTIVE: Despite guidelines recommending against opioids as first-line treatment for acute migraine, meperidine is the agent used most commonly in North American emergency departments. Clinical trials performed to date have been small and have not arrived at consistent conclusions about the

STUDY OBJECTIVE: Despite guidelines recommending against opioids as first-line treatment for acute migraine, meperidine is the agent used most commonly in North American emergency departments. Clinical trials performed to date have been small and have not arrived at consistent conclusions about the efficacy of meperidine. We performed a systematic review and meta-analysis to determine the relative efficacy and adverse effect profile of opioids compared with nonopioid active comparators for the treatment of acute migraine. METHODS: We searched multiple sources (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and LILACS, emergency and headache medicine conference proceedings) for randomized controlled trials comparing parenteral opioid and nonopioid active comparators for the treatment of acute migraine headache. Our primary outcome was relief of headache. If this was unavailable, we accepted rescue medication use or we transformed visual analog scale change scores by using an established procedure. We grouped studies by comparator: a regimen containing dihydroergotamine, antiemetic alone, or ketorolac. For each study, we calculated an odds ratio (OR) of headache relief and then assessed clinical and statistical heterogeneity for the group of studies. We then pooled the ORs of headache relief with a random-effects model. RESULTS: From 899 citations, 19 clinical trials were identified, of which 11 were appropriate and had available data. Four trials involving 254 patients compared meperidine to dihydroergotamine, 4 trials involving 248 patients compared meperidine to an antiemetic, and 3 trials involving 123 patients compared meperidine to ketorolac. Meperidine was less effective than dihydroergotamine at providing headache relief (OR=0.30; 95% confidence interval [CI] 0.09 to 0.97) and trended toward less efficacy than the antiemetics (OR=0.46; 95% CI 0.19 to 1.11); however, the efficacy of meperidine was similar to that of ketorolac (OR=1.75; 95% CI 0.84 to 3.61). Compared to dihydroergotamine, meperidine caused more sedation (OR=3.52; 95% CI 0.87 to 14.19) and dizziness (OR=8.67; 95% CI 2.66 to 28.23). Compared to the antiemetics, meperidine caused less akathisia (OR=0.10; 95% CI 0.02 to 0.57). Meperidine and ketorolac use resulted in similar rates of gastrointestinal adverse effects (OR=1.27; 95% CI 0.31 to 5.15) and sedation (OR=1.70; 95% CI 0.23 to 12.72). CONCLUSION: Clinicians should consider alternatives to meperidine when treating acute migraine with injectable agents.

New York City and Los Angeles County have the largest health systems in the United States, but they differ significantly in structure. This study compares and analyzes the structural and workforce differences between the two. The health system in New York City is centered around its large hospitals,

New York City and Los Angeles County have the largest health systems in the United States, but they differ significantly in structure. This study compares and analyzes the structural and workforce differences between the two. The health system in New York City is centered around its large hospitals, and as a result New York employs many more health workers than Los Angeles County, where the health system is centered around physician groups. Health care is a significant contributor to the economy of both areas, but a larger contributor to the economy in New York City.

The public hospital system in Los Angeles County, California, is in the midst of a major fiscal crisis that has already led to a serious reduction of capacity and could continue to worsen. Given the importance of the public system in a county where 30 percent of the population is uninsured and priva

The public hospital system in Los Angeles County, California, is in the midst of a major fiscal crisis that has already led to a serious reduction of capacity and could continue to worsen. Given the importance of the public system in a county where 30 percent of the population is uninsured and private hospitals provide very little uncompensated care, what happens in L.A. County is a harbinger for other cities and counties in the United States. This article highlights the issue of the extent to which local taxpayers, as opposed to state or federal taxpayers, are responsible for the continued operation of public hospitals and safety-net facilities in their communities.

In the close to medium future, the life sciences might permit a vast extension of the human life span. I will argue that this is a very desirable development for the individual person. The question whether death is a harm to the dying is irrelevant here. All it takes is that being alive is good for

In the close to medium future, the life sciences might permit a vast extension of the human life span. I will argue that this is a very desirable development for the individual person. The question whether death is a harm to the dying is irrelevant here. All it takes is that being alive is good for the living person and not being alive is not good for anyone. Thus, living persons who expect to live on happily are rationally required to want to stay alive. Eventual uncertainty whether it will be possible to be happy in the future provides no objection, but rather an incentive to try. This view, however, may be naive in assuming that persons are unchanging entities that exist separately from their psychological information. Objections have been derived from reductionistic views that value our future experiences in a way that declines with time, so that there will be a future point beyond which only negligible value accrues. If we adopt such a view, then we cannot now be concerned to have experiences beyond that point. I argue that these arguments fail to take into account all the reasons we might have to be concerned for the future and all kinds of such concern that come from them. The adoption of a plausible reductionistic account can arguably weaken our concern for the future and certainly change its quality in important ways. But this provides no objection to the desire to live forever, nor to live at all.