Citations

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.

AbstractThe etiology, prognosis, and optimal management of primary gastric carcinoids remain controversial. Records of 36 consecutive patients with gastric carcinoid (15 men) were reviewed retrospectively between 1975 and 1990. Follow‐up was complete in 97% of cases. Mean age at diagnosis was 58.4 years (range 24–82 years). The clinical presentations included anemia (72%), pain (69%), and carcinoid syndrome (11%). Associated autoimmune and endocrine abnormalities were common and included atrophic gastritis (67%), pernicious anemia (58%), hypothyroidism (39%), diabetes (19%), Addison's disease (6%), and hyperparathyroidism (6%). Lesions were nonantral in 78%, involving only the corpus in 42%, the fundus in 28%, and only the antrum in 8%; 42% were multiple. Urinary 5‐hydroxyindoleacetic acid (5‐HIAA) and serum gastrin levels were elevated in 17% and 50% of those tested, respectively. Histologic examination revealed that 28% of lesions were ≥2 cm, and 33% had liver metastases on presentation or developed them during follow‐up. Eight patients (22%) died of tumor with a median survival of 39 months. The presence of metastases, atypical histology, serosal involvement, and size > 2 cm were adverse prognostic factors. In patients without hypergastrinemia (n=6), 66% developed metastases, 60% had elevated 5‐HIAA, and 50% died of carcinoid tumor. In sharp contrast, those patients with hypergastrinemia and “typical” gastric carcinoids (n=15), metastases and death did not occur (p<0.003 and p < 0.005, respectively, compared with eugastrinemic patients). In the latter group (hypergastrinemia and typical histology), pernicious anemia was common (73%); solitary lesions and serosal penetration were seen comparatively less often (33% versus 100%, p<0.005 and 0% versus 33%, p<0.05, respectively); and no lesion measured > 2.0 cm compared to 66% in the group without elevated gastrin (p<0.002). No patient with hypergastrinaemia had elevated levels of 5‐HIAA. Overall survival at 5 and 10 years was 58% and 28%, respectively. Survival was 80% at 5 and 10 years in the hypergastrinemic group. Gastric carcinoid tumors that are histologically atypical, large (>2 cm), or present without elevated gastrin are potentially lethal and require aggressive therapy. In contrast, gastric carcinoids with typical histology and hypergastrinemia are rarely lethal, and conservative management with local excision and close observation is appropriate.

ABSTRACTSuperantigen peptide antagonists failed to block T-cell activation and cytokine production as well as toxic shock induced by staphylococcal enterotoxin B (SEB) in HLA class II transgenic mice. They also failed to inhibit the binding of SEB to HLA class II molecules as well as activation of human T lymphocytes in vitro.