Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia

Context  Conventional colonoscopy is the best available method for detection of colorectal cancer; however, it is invasive and not without risk. Computed tomographic colonography (CTC), also known as virtual colonoscopy, has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers. Objective  To assess the accuracy of CTC in a large number of participants across multiple centers. Design, Setting, and Participants  A nonrandomized, evaluator-blinded, noninferiority study design of 615 participants aged 50 years or older who were referred for routine, clinically indicated colonoscopy in 9 major hospital centers between April 17, 2000, and October 3, 2001. The CTC was performed by using multislice scanners immediately before standard colonoscopy; findings at colonoscopy were reported before and after segmental unblinding to the CTC results. Main Outcome Measures  The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm. Secondary outcomes included detection of all lesions, detection of advanced lesions, possible technical confounders, participant preferences, and evidence for increasing accuracy with experience. Results  A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures; 104 participants had lesions sized at least 6 mm. The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants were without any lesion sized at least 6 mm. The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively. Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC varied considerably between centers and did not improve as the study progressed. Participants expressed no clear preference for either technique. Conclusions  Computed tomographic colonography by these methods is not yet ready for widespread clinical application. Techniques and training need to be improved.      

An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study)

Maximal benefits of coronary reperfusion after acute myocardial infarction (AMI) with ST-segment elevation may be attenuated by neutrophil-mediated reperfusion injury. Inflammatory mediators released from potentially viable myocytes cause activation of neutrophils, which traverse the endothelium and enter the myocardium. This process involves interaction between the neutrophil-expressed CD11/CD18 and endothelial-expressed intercellular adhesion molecule-1 (ICAM-1). Preclinical studies have shown that monoclonal antibodies (MAb) to CD18 can limit infarct size and preserve left ventricular function. We sought to determine the initial clinical safety and tolerability of Hu23F2G (LeukArrest), a humanized MAb to CD11/CD18, in patients with AMI who underwent percutaneous transluminal coronary angioplasty (PTCA). Sixty patients with AMI were randomized to low- (0.3 mg/kg) or high-dose (1.0 mg/kg) Hu23F2G or to placebo immediately before PTCA. We found no clinically significant differences in vital signs, physical examination, laboratory evaluation, or need for subsequent cardiac interventions. In Hu23F2G treatment groups, serum concentration of Hu23F2G increased rapidly to 3,234 +/- 1,298 microg/L (low-dose group) and 15,558 +/- 4409 microg/L (high-dose group) between 5 and 60 minutes, then declined over 72 hours to near-baseline values. Myocardial single-photon emission computed tomographic imaging 120 to 260 hours after PTCA showed no statistically significant differences in final left ventricular defect size. Hu23F2G was well tolerated, with no increase in adverse events, including infections. Thus, Hu23F2G appears safe and well tolerated in patients undergoing PTCA for AMI.     

Continuous 12-lead electrocardiographic monitoring in an emergency department chest pain unit: an assessment of potential clinical effect

STUDY OBJECTIVES: Continuous 12-lead serial ECG monitoring has been proposed to assist in the evaluation of patients with acute coronary syndrome and nondiagnostic ECG in an emergency department chest pain unit. However, the ability of serial ECG to detect acute coronary syndrome and its benefit in addition to a standard protocol has not been established. We evaluate the ability of continuous 12-lead ECG to detect acute coronary syndrome, assess the incremental benefit of the serial ECG in association with a set protocol in an ED chest pain unit, and evaluate whether serial ECG changes could be considered as prognostic factors. METHODS: Patients who met Agency for Health Care Policy and Research guidelines for intermediate risk for short-term cardiovascular event unstable angina were prospectively studied in the chest pain unit. Patients were monitored with the Mortara Instruments ELI 100 STM continuous 12-lead ECG system with ST-segment analysis. ST-segment changes of greater than 100 microV in 2 or more contiguous leads or greater than 200 microV in 1 lead were considered positive. Data were compared with serial serum cardiac markers, cardiac function study results, angiographic results, and 30-day outcome results. RESULTS: One hundred nineteen patients had serial ECG applied. The median duration of monitoring was 4.2 hours. Forty patients were given a diagnosis of acute coronary syndrome. Chest pain unit protocol detected 52 patients, and 23 were given a diagnosis of acute coronary syndrome (sensitivity 58%; specificity 63%). Sixteen patients had ST-segment changes of greater than 100 microV or greater than 200 microV, and 9 were given a diagnosis of acute coronary syndrome. The addition of the serial ECG to the chest pain unit protocol increased the sensitivity to 65% and decreased the specificity to 58%. Two patients with ST-segment changes but none without ST-segment changes had an adverse cardiac event, yielding a sensitivity of 100% and a specificity of 88%. CONCLUSION: Serial ECG is of limited value in the diagnostic evaluation of intermediate-risk patients managed in the chest pain unit with a standard protocol. However, when ST-segment changes are present, they indicate an increased likelihood for an adverse cardiac event.     

Blasts from elderly acute myeloid leukemia patients are characterized by low levels of culture- and drug-induced apoptosis

Increasing evidence suggests that the biology of acute myeloid leukemia (AML) may differ between older and younger patients, with a higher incidence of antecedent myelodysplasia, unfavorable cytogenetic abnormalities, and multidrug resistance seen in the elderly. Abrogation of apoptosis in response to cytotoxic medications is associated with drug resistance in AML, as is expression of bcl-2, an important anti-apoptotic protein. We hypothesized that blasts from elderly (> or = 55 years) and young adult AML patients might have different levels of apoptotic and cell cycle responses to chemotherapeutic agents, as well as different levels of proliferation and of bcl-2 protein expression. Therefore, we cultured bone marrow leukemia samples from previously untreated elderly (n=33) and young (n=21) AML patients for 48 h and then measured apoptosis, bcl-2 protein levels, cell cycle distributions, and expression of a proliferation marker, proliferating cellular nuclear antigen (PCNA) in multi-parametric flow cytometry assays. In some experiments, leukemia samples were exposed to cytarabine (Ara-C) or daunomycin (DNR) for the last 16-18 h of the culture period. In comparison to samples from young patients, cultured samples from elderly AML patients had a higher fraction of viable cells, as measured by Trypan blue exclusion, higher PCNA expression, and significantly less culture-induced and drug-induced apoptosis. The mean apoptosis after culture was 13% for elderly AML samples, versus 20% for young AML samples (P=0.009). Similarly, the mean apoptosis after Ara-C was lower in elderly than in young AML samples, 13 versus 28% (P=0.001), as was the mean apoptosis after DNR, 15 versus 26% (P=0.012). Diminished apoptotic responses in elderly AML cells were not consistently associated with high bcl-2 levels at thaw or bcl-2 levels increased by culture. These data suggest that new therapies should be developed to overcome abrogated apoptosis, particularly in elderly AML patients.     

ENDOTHELIAL CELL CULTURE AND SEEDING OF PROSTHETIC VASCULAR GRAFTS: AN EXPERIMENTAL STUDY

Current synthetic vascular prostheses do not acquire lining of vascular endothelium in humans or dogs. Endothelial seeding of vascular grafts has been proposed as a means of reducing the thrombogenicity of these grafts. We examined feasibility of cultivating endothelial cells (EC) by tissue culture technique and their subsequent seeding onto small diameter polytetra fluoroethylene (PTFE) grafts. Twenty adult dogs underwent common carotid artery interposition with 4 mm PTFE grafts. Ten dogs received seeded and the remaining ten received unseeded grafts. Grafts were removed at 4 and 12 weeks and their gross/morphological features compared. Cumulative patency rates for seeded grafts were 70% as compared to unseeded ones 30%. Seeded grafts were completely surfaced with a mono-layer of endothelium by 4 weeks. Small graft patency appears to be related to the establishment of an endothelial surface, the development of which is clearly facilitated by seeding with autogenous endothelium.KEY WORDS: Endothelial cell seeding, Vascular grafts     

Idiopathic Atrial Fibrillation: Prevalence,Course, Treatment,and Prognosis

Journal of Thrombosis and Thrombolysis -     

Parapelvic lymph cyst in a renal allograft mimicking hydronephrosis: CT diagnosis

Lymphoceles are common complications of renal transplantation and usually arise between the bladder and the transplant kidney. A rare case of a parapelvic lymphocyst in a renal allograft is presented that sonographically mimicked hydronephrosis but was correctly diagnosed by CT.