Citations

Background— Sirolimus-eluting stents (SESs) reduce angiographic restenosis in patients with focal, native coronary artery stenoses. This study evaluated the usefulness of SESs in complex native-vessel lesions at high risk for restenosis. Methods and Results— Angiographic follow-up at 240 days was obtained in 701 patients with long (15- to 25-mm) lesions in small-diameter (2.5- to 3.5-mm) native vessels who were randomly assigned to treatment with SESs or bare-metal stents (BMSs) in the SIRIUS trial. Quantitative angiographic measurements of minimal lumen diameter and percent diameter stenosis were obtained within the treated segment, within the stent, and within its 5-mm proximal and distal edges. Patients treated with SESs had lower rates of binary (>50% diameter stenosis) angiographic restenosis within the segment (8.9% versus 36.3% with the BMS; P <0.001) and within the stent (3.2% versus 35.4% with the BMS; P <0.001). SESs were associated with significantly less late lumen loss within the treated segment, within the stent, and within its 5-mm proximal and distal edges (all P <0.001). The reduction of restenosis with the SES was consistent in patients at risk for restenosis, including those with small vessels, long lesions, and diabetes mellitus. The frequency of late aneurysms was similar in the 2 groups. Conclusions— Compared with BMSs, SESs reduced angiographic late lumen loss within the stent and its adjacent 5-mm margins in patients with complex native-vessel lesions.

The objectives of this study were to determine the effectiveness of a novel, trypsinized density gradient treatment designed to remove viruses from semen and to evaluate sperm viability after treatment. Exp. 1: Cryopreserved human semen (n = 6 donors) was layered on 2-mL columns of 45% Isolate (Irvine Scientific, Santa Ana, CA, USA) with or without 0.25% trypsin (trypsin-exposed and control, respectively), which overlaid 2-mL columns of 90% Isolate with or without 10 µg/mL soy-based trypsin inactivator (Sigma, St. Louis, MO, USA) and centrifuged (700g for 30 min). The layering of multiple density gradients is facilitated by a novel polypropylene tube insert, which also prevents contamination when extracting treated sperm (USA and international patents pending). Pellets were washed and then incubated at room temperature. Sperm were examined (motility and supravital staining) at 0, 2, 24, and 48 h post-treatment and the results evaluated using Wilcoxon Signed Rank and Rank Sum tests. Exp. 2: A cytopathic cell (MT-2) assay was conducted (6 replicates) to determine the effect of trypsin (1-min exposure) on HIV-1 RNA infectivity. Viral replication was assessed by syncytium formation and p24 antigen production. Exp. 3: Two pools of fresh human semen (N1 = 3 and N2 = 8 donors) were inoculated (1:1) with 1 × 108 copies/mL of cultured HIV-1 RNA, and one pool (N2) was inoculated (1:1) with plasma collected from patients infected with either Hepatitis B DNA (HBV) or C (HCV) RNA viruses; spiked and non-spiked aliquots were processed as in Exp. 1. Treated sperm pellets were analyzed for HIV-1 or HBV and HCV concentrations by the Bayer Versant branched DNA (bDNA; version 3.0) and/or the Roche Amplicor quantitative RT-PCR (1.5 ultrasensitive) assays at Toga Laboratories (Pty), Ltd. (Edenvale, South Africa). As a result of Exp. 1, there was significantly (P &lt; 0.05) lower motility (but not supravital staining) between trypsin-treated and control sperm at 0 h (58.0 vs. 69.3%) and 2 h (54.7 vs. 62.9%) post-washing; however, no differences were noted after 24 h (P &gt; 0.05). In Exp. 2, trypsin exposure affected HIV-1 RNA infectivity negatively as compared to controls in terms of MT-2 cell syncytium formation and p24 antigen production. Results of the bDNA and/or RT-PCR assays in Exp. 3 indicated that the procedure effectively reduced HIV-1, HBV, and HCV viral copies in the spiked semen samples to undetectable levels or levels below clinical relevance. In conclusion, the novel trypsin density gradient procedure was effective for removing HIV-1, HBV and HCV from spiked semen without markedly affecting sperm survival. Extrapolation of these results to natural infections may be unfounded for viruses (e.g. HBV) that are thought to integrate into sperm chromatin.

AbstractFocal nodular hyperplasia (FNH) and hepatocellular adenoma (HA) are uncommon benign hepatic tumors that continue to pose diagnostic and therapeutic challenges. An update of a recent Mayo Clinic experience is presented to highlight the management of patients harboring these neoplasms. A marked female predominance was seen. Incidental diagnosis was more prevalent with FNH, whereas symptomatic presentation was typical of HA. The frequency of oral contraceptive steroid use was similar regardless of tumor histology. Preoperative diagnosis remains difficult. Scintigraphy proved most specific, and ultrasonography and computed tomography were equally sensitive. Resection was employed in most patients. There was no mortality and minimal morbidity. Selective observation of FNH was uneventful, but resolution of HA after abstinence of oral contraceptive steroids was uncommon. These findings and data from the literature support selective management of benign liver tumors.

Oncology services have been provided by telemedicine from the University of Kansas Medical Center (KUMC) for almost 10 years. We have analysed the costs associated with providing tele-oncology clinics to a rural Kansas town for two fiscal years, 1995 and 2000. The aim was to compare recent tele-oncology costs with those of the first year of tele-oncology practice. A study conducted in 1995 showed that the average cost was $812 per telemedicine consultation. Data from fiscal year 2000 showed that the average cost was $410 per telemedicine consultation, a decrease of almost 50%. As the tele-oncology practice in Kansas continues to grow, it can be expected that the costs associated with providing tele-oncology services will continue to decline.

Abstract Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors that are usually benign, but which may also present as or develop into a malignancy. Predicting such behavior is notoriously difficult and there are currently no curative treatments for malignant tumors. This report follows from a workshop at the Banbury Conference Center, Cold Spring Harbor, New York, on the 16th–18th November 2003, held to review the state of science and to facilitate future progress in the diagnosis and treatment of malignant pheochromocytoma. The rarity of the tumor and the resulting fragmented nature of studies, typically involving small numbers of patients, represent limiting factors to the development of effective treatments and diagnostic or prognostic markers for malignant disease. Such development is being facilitated by the availability of new genomics-based tools, but for such approaches to succeed ultimately requires comprehensive clinical studies involving large numbers of patients, stringently collected clinical data and tumor samples, and interdisciplinary collaborations among multiple specialist centers. Nevertheless, the well-characterized hereditary basis and the unique functional nature of these neuroendocrine tumors provide a useful framework that offers advantages for establishing the pathways of tumorigenesis and malignancy. Such findings may have relevance for understanding the basis of other more common malignancies where similar frameworks are not available. As the relevant pathways leading to pheochromocytoma are established it should be possible to take advantage of the new generation of drugs being developed to target specific pathways in other malignancies. Again the success of this will require well-designed and coordinated multicenter studies.

ABSTRACT The initiation of reverse transcription and nucleocapsid assembly in hepatitis B virus (HBV) depends on the specific recognition of an RNA signal (the packaging signal, ε) on the pregenomic RNA (pgRNA) by the viral reverse transcriptase (RT). RT-ε interaction in the duck hepatitis B virus (DHBV) was recently shown to require the molecular chaperone complex, the heat shock protein 90 (Hsp90). However, the requirement for RT-ε interaction in the human HBV has remained unknown due to the inability to obtain a purified RT protein active in specific ε binding. We now report that Hsp90 is also required for HBV RT-ε interaction. Inhibition of Hsp90 led to diminished HBV pgRNA packaging into nucleocapsids in cells, which depends on RT-ε interaction. Furthermore, using truncated HBV RT proteins purified from bacteria and five purified Hsp90 chaperone factors, we have developed an in vitro RT-ε binding assay. Our results demonstrate that Hsp90, in a dynamic process that was dependent on ATP hydrolysis, facilitated RT-ε interaction in HBV, as in DHBV. Specific ε binding required sequences from both the amino-terminal terminal protein and the carboxy-terminal RT domain. Only the cognate HBV ε, but not the DHBV ε, could bind the HBV RT proteins. Furthermore, the internal bulge, but not the apical loop, of ε was required for RT binding. The establishment of a defined in vitro reconstitution system has now paved the way for future biochemical and structural studies to elucidate the mechanisms of RT-ε interaction and chaperone activation.

Background— The primary aim and central hypothesis of the study are that a designated syncope unit in the emergency department improves diagnostic yield and reduces hospital admission for patients with syncope who are at intermediate risk for an adverse cardiovascular outcome. Methods and Results— In this prospective, randomized, single-center study, patients were randomly allocated to 2 treatment arms: syncope unit evaluation and standard care. The 2 groups were compared with χ 2 test for independence of categorical variables. Wilcoxon rank sum test was used for continuous variables. Survival was estimated with the Kaplan-Meier method. One hundred three consecutive patients (53 women; mean age 64±17 years) entered the study. Fifty-one patients were randomized to the syncope unit. For the syncope unit and standard care patients, the presumptive diagnosis was established in 34 (67%) and 5 (10%) patients ( P <0.001), respectively, hospital admission was required for 22 (43%) and 51 (98%) patients ( P <0.001), and total patient-hospital days were reduced from 140 to 64. Actuarial survival was 97% and 90% ( P =0.30), and survival free from recurrent syncope was 88% and 89% ( P =0.72) at 2 years for the syncope unit and standard care groups, respectively. Conclusions— The novel syncope unit designed for this study significantly improved diagnostic yield in the emergency department and reduced hospital admission and total length of hospital stay without affecting recurrent syncope and all-cause mortality among intermediate-risk patients. Observations from the present study provide benchmark data for improving patient care and effectively utilizing healthcare resources.

AbstractAs refinement of technetium‐99m 2‐methoxyisobutyl isonitrile‐scintigraphy (MIBI)‐scintigraphy of parathyroid glands has continued since its initial use in 1989, the sensitivity, specificity, and overall accuracy of the technique have improved greatly, approaching 100% for larger, solitary adenomas. Preoperative use of sestamibi scintigraphy has become commonplace and allows surgeons the option of a minimally invasive, or focused approach for their patients with primary hyperparathyroidism. Intraoperative use of the gamma probe based on sestamibi localization has not caught on due to lesser accuracy, cumbersome gamma probes, small doses of radiation exposure for patients and staff, and the greater accuracy and current confidence in intraoperative parathormone (PTH) monitoring. However, with the potential for smaller and more accurate gamma probes that truly assist in localizing abnormal parathyroid glands, the potential for cost reduction by shortening operative times, avoiding expensive PTH assays, and eliminating the need for pathologic analysis, gamma scintigraphy may yet become a viable option for many parathyroid surgeons.