Citations

The purpose of this paper is to describe the intraoperative management of a type IIIb endoleak after deployment of a bifurcated endograft in a patient with narrow iliac access vessels. A 62-year-old man underwent elective endovascular repair (EVAR) of a 53 mm abdominal aortic aneurysm. After device deployment, a large IIIb endoleak, arising from the main body of the device, was visualized. Narrow iliac vessels precluded deployment of a second bifurcated graft, and the endoleak was successfully excluded with an aortomonoiliac device, followed by contralateral iliac occlusion and subsequent creation of a femorofemoral bypass. At 1-year follow-up, the aneurysm remains excluded and is decreasing in size. Type III endoleaks are a known complication of EVAR, requiring immediate treatment through their association with aneurysm enlargement and rupture. If an additional bifurcated graft cannot be used, aortomonoiliac conversion represents a feasible endovascular alternative treatment for type III endoleaks, other than conversion to open surgical repair. Therefore, aortomonoiliac converters with appropriate occluder devices should be readily available during deployment of bifurcated devices.

Background:There has been increasing recognition of the detrimental effect of peripheral arterial disease (PAD) on the health of Americans, and yet there is no common national program of public PAD education designed to diminish this effect. Format:To heighten awareness of this problem, a 2-day PAD Public Education Strategy Meeting was recently attended by representatives of 17 professional societies and public health associations whose missions support the prevention, diagnosis, treatment, and rehabilitation of vascular diseases. This Public Education Strategy Meeting was intended to provide the rationale and structure to create a national PAD public awareness campaign to diminish the health effect of PAD and to improve cardiovascular outcomes in the United States. This document (1) provides the rationale for creation of a national PAD public education program; (2) reviews the development and success of national hypertension, hypercholesterolemia, and Women's Heart Health public education programs as models of educational efficacy; (3) elucidates how the work of many vascular professionals has led to a national consensus for creation of a national PAD public educational program; (4) provides an overview of the National Heart, Lung, and Blood Institute PAD education meeting; and (5) outlines the “next steps” required to accomplish these goals. Outcome:This meeting achieved consensus that we share responsibility for developing accurate, unified messages to promote PAD awareness and improved care. Participants agreed that the creation of such messages should be linked to plans to disseminate them to all Americans at risk. A consensus was reached that such messages, when commonly created and offered to the public, are most likely to achieve the rewards in better health that all Americans deserve. The Vascular Disease Foundation, a not-for-profit foundation whose mission includes public education about the prevention, diagnosis, treatment, and rehabilitation of PAD, will devote its resources to guide a new coalition in this process and to create a national PAD awareness campaign. During 2003 and 2004, the coalition will create the organizational underpinnings and time line for what will undoubtedly be a multiyear effort. Conclusion:Participants of the Public Education Strategy Meeting agreed to create a broad coalition to develop a National PAD Public Awareness Program, with the objectives to develop and disseminate public education messages on PAD. A successful national PAD education program will contribute to creation of a broader mandate to improve global cardiovascular health in the United States.

Stent-grafts are ideally terminated within the common iliac artery (CIA). However, CIA ectasia may require hypogastric artery occlusion, with stent-graft extension to the external iliac artery. Alternatively, the diameter of the distal stent-graft may be increased, or flared, to allow exclusion of the abdominal aortic aneurysm. This report details the authors’ experience with this technique. Forty-one patients received bifurcated stent-grafts (BSG): 20 received an AneuRx device, and 21 received a Zenith device. CIA ectasia (diameter 15–25 mm) was treated with a distal flare of 2–4 mm greater than the CIA diameter. Patients were followed up with computed tomography scan at 1, 6, and 12 months. Statistical analysis was performed using ANOVA within groups and unpaired two-tailed t test between groups. A p value of <0.05 was considered significant. Eight of 20 patients (40%) (11 CIA) received an AneuRx device and 13/21 (62%) (17 CIA) received a Zenith device, with a distal flare. Values are (n) mean (mm) ± SE. There were no deaths, endoleaks, migrations, or conversions to open repair. Follow-up mean was 24.7 and 20.6 (range 15–28) months for AneuRx and Zenith groups, respectively. In comparing initial and 12-month CIA diameters, AneuRx grafts 20 ±0.8 vs 21.5 ±1.0 were not significantly different, p= 0.2, nor was the same comparison for Zenith, 17 ±0.5 vs 19.1 ±0.4, significant, p= 0.57. At a mean follow-up of 12 months, distal flare of iliac limbs with either AneuRx or Zenith devices affords a seal for CIA ectasia and/or aneurysms complicating EVAR.

Abstract Previous studies have suggested that the proinflammatory cytokine, TNF-α, contributes to airway hyperresponsivness by altering airway smooth muscle (ASM) Ca2+ responses to agonist stimulation. The present study examined the effects of TNF-α on Ca2+ influx pathways in cultured human ASM cells (HASMCs). Proteins encoded by the transient receptor potential (TRP) gene family function as channels through which receptor-operated and store-operated Ca2+ entry (SOCE) occur. In the present study, the presence of TRPC1, TRPC3, TRPC4, TRPC5, and TRPC6 mRNA and protein expression was confirmed in cultured HASMCs using RT-PCR and Western blot analysis. TNF-α treatment significantly increased TRPC3 mRNA and protein levels in HASMCs as well as SOCE. TNF-α treatment also increased both the peak and plateau intracellular Ca2+ concentration responses in HASMCs elicited by acetylcholine and bradykinin. The effects of TNF-α treatment on SOCE and agonist-induced intracellular Ca2+ concentration responses were attenuated using small interfering RNA transfection, which knocked down TRPC3 expression. Thus, in inflammatory airway diseases, TNF-α treatment may result in increased myocyte activation due to altered Ca2+ influx pathways. These results suggest that TRPC3 may be an important therapeutic target in inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease.

ABSTRACT The activity of garenoxacin was compared to that of levofloxacin or penicillin in a rabbit model of Streptococcus mitis group (penicillin MIC, 0.125 μg/ml) and Streptococcus sanguinis group (penicillin MIC, 0.25 μg/ml) endocarditis. Garenoxacin and levofloxacin had MICs of 0.125 and 0.5 μg/ml, respectively, for both study isolates. Rabbits with catheter-induced aortic valve endocarditis were given no treatment, penicillin at 1.2 × 10 6 IU/8 h intramuscularly, garenoxacin at 20 mg/kg of body weight/12 h intravenously, or levofloxacin at 40 mg/kg/12 h intravenously. For both isolates tested, garenoxacin area under the curve (AUC)/MIC and maximum concentration of drug in serum ( C max )/MIC ratios were 368 and 91, respectively. Rabbits were sacrificed after 3 days of treatment; cardiac valve vegetations were aseptically removed and quantitatively cultured. For S. mitis group experimental endocarditis, all studied antimicrobial agents were more active than no treatment ( P < 0.001), whereas for S. sanguinis group endocarditis, no studied antimicrobial agents were more active than no treatment. We conclude that AUC/MIC and C max /MIC ratios may not predict activity of some quinolones in experimental viridans group endocarditis and that garenoxacin and levofloxacin may not be ideal choices for serious infections caused by some quinolone-susceptible viridans group streptococci.

Abstract Purpose: MV-CEA is an oncolytic measles virus currently being tested in patients with ovarian cancer and whose propagation can be monitored by measuring blood carcinoembryonic antigen (CEA) levels. MV-NIS is an oncolytic measles virus coding for the thyroidal sodium iodide symporter (NIS) whose propagation can be mapped by serial radioiodine imaging. Expression of both CEA and NIS genes from a single virus would combine sensitive, quantitative expression monitoring (CEA) with radioisotopic expression mapping (NIS). Because of the unfavorable replication kinetics of measles viruses expressing both CEA and NIS, we explored the feasibility of combining MV-CEA with MV-NIS for comprehensive virotherapy monitoring in ovarian cancer. Experimental Design and Results: Mice implanted with i.p. SKOV3ip.1 ovarian cancer xenografts received MV-CEA alone, MV-NIS alone, or a combination of MV-CEA plus MV-NIS. Viral gene expression was monitored by measuring blood CEA levels, and the location of virus-infected cells was monitored by gamma camera imaging. Surprisingly, mice receiving the combination of MV-CEA plus MV-NIS showed greatly superior responses to therapy, but this was associated with 10-fold lower plasma levels of CEA compared with mice treated with MV-CEA alone. In vitro studies showed superior replication kinetics of MV-NIS relative to MV-CEA. The gamma camera scans were considerably less sensitive than the plasma CEA marker for monitoring virus infection. Conclusions: Dual therapy with MV-CEA and MV-NIS is superior to treatment with either virus alone, and it allows noninvasive monitoring of virotherapy via soluble marker peptide and gamma camera imaging. This has important implications for the clinical development of oncolytic measles viruses.

Abstract Purpose: Vinorelbine (Navelbine) is an orally absorbable Vinca with broad antitumor activity. It differs from other Vinca in that it is structurally modified on the catharanthine nucleus and has differential actions on tubulin that render it less neurotoxic than other compounds in this class. We conducted a phase I study of vinorelbine given the activity of Vinca alkaloids in many pediatric tumors. Experimental Design: We evaluated the safety and pharmacokinetics of oral and i.v. vinorelbine administered weekly × 6 in children (age, 2-17 years) with different tumors. Patients with disease involvement in the bone marrow were eligible but were stratified and dose-escalated separately. Oral vinorelbine (week 1) was administered as liquid-filled gelatin capsules at thrice the i.v. dose. Intravenous vinorelbine doses of 24 to 37.5 mg/m2 were administered on weeks 2 to 6. Results: The dose-limiting toxicity in patients without marrow involvement was reversible neutropenia. Common nonhematologic toxicities included ≤ grade 2 nausea/vomiting and increased hepatic transaminases. A higher mean i.v. ClTB was observed (1.75 ± 1.0 L/h/kg) compared with adult reports, with a mean t1/2B of 16.5 ± 9.7 hours. Mean oral bioavailability was 28.5 ± 22.5%. The apparent oral clearance (12.1 ± 13.0 L/h/kg) and volume of distribution (69.4 ± 30.6 L/kg) were substantially higher than in adults given similar oral doses. Conclusions: The maximum tolerated dose in children without bone marrow involvement was 30 mg/m2, similar to that reported in adults, with myelosuppression being the dose-limiting toxicity. Higher plasma clearance resulted in lower area under the plasma concentration-time curves at a given dose compared with that reported in adults.

Abstract Recent experimental evidence has shown that catechol estrogens can be activated through metabolism to form depurinating DNA adducts and thereby initiate cancer. Limited data are available regarding this pathway in epithelial ovarian cancer. We conducted a case-control study of 503 incident epithelial ovarian cancer cases at the Mayo Clinic in Rochester, MN, and Jacksonville, FL, and a 48-county region in North Carolina. Six hundred nine cancer-free controls were frequency matched to the cases on age, race, and residence. After an interview to obtain data on risk factors, a sample of blood was collected for DNA isolation. Subjects were genotyped for seven common single nucleotide polymorphisms in four genes involved in catechol estrogen formation (CYP1A1 and CYP1B1) or conjugation (COMT and SULT1A1). Data were analyzed using logistic regression, stratified by race, and with adjustment for design factors and potential confounders. None of the individual genotypes were significantly associated with ovarian cancer risk. However, an oligogenic model that considered the joint effects of the four candidate genes provided evidence for an association between combinations of these genes and ovarian cancer status (P = 0.015). Although preliminary, this study provides some support for the hypothesis that low-penetrance susceptibility alleles may influence risk of epithelial ovarian cancer.

Abstract Rationale Although the serial dilution technique for quantitative culture of bronchoalveolar fluid is considered to be the gold standard for the diagnosis of ventilator-associated pneumonia, it is more labor intensive than the calibrated loop technique. Objective We sought to determine the agreement between the calibrated loop and serial dilution techniques in the diagnosis of ventilator-associated pneumonia. Methods We prospectively measured bacterial colony counts by the serial dilution and calibrated loop techniques in 121 bronchoalveolar lavage samples of 104 patients with suspected ventilator-associated pneumonia. Measurements and Main Results At the time of bronchoscopy, patients had received mechanical ventilation for a median of 8 d. Patients were receiving antibiotics when 90 of the 121 (74.4%) bronchoalveolar samples were obtained. The colony counts of 13 bacterial isolates were too numerous to count by the calibrated loop technique; by serial dilution technique, their counts ranged from 4.70 to 6.74 log10 cfu/ml. Fifty other bacteria had paired colony counts measured by each of the two techniques: the bias (95% confidence interval) between the two techniques was −0.380 (−0.665 to −0.095) log10 cfu/ml, with precision of 1.002 log10 cfu/ml and 95% limits of agreement of −2.344 to 1.584 log10 cfu/ml. Using the threshold of 4 log10 cfu/ml as a criterion for the diagnosis of ventilator-associated pneumonia, there was discordance only for one bacterial organism between the two techniques. Conclusions The calibrated loop technique can be used for the diagnosis of ventilator-associated pneumonia using bronchoalveolar lavage fluid.