Flavone acetic acid as a modifier of endothelial cell function.

Flavone acetic acid (FAA) causes significant regression of larger established tumors in murine systems in vivo, but is only slightly toxic in vitro. This in vivo effect is thought to be indirect, or immunological, rather than a direct cytotoxic effect on tumor cells. Using the WHFIB fibrosarcoma, which grows both in vivo and in vitro, and the murine endothelial cell line B10, we have studied the effect of FAA on the survival of tumor and endothelial cells in vitro. The times taken for 1 mg ml-1 FAA to reduce survival to 0.1 surviving fraction were 63 hr for B10 and greater than 85 hr for WHFIB in vitro. WHFIB tumors in vivo were more sensitive than tumor cells in vitro, a single dose of 150 mg kg-1 FAA inducing a tumor growth delay of 10 days at treatment size + 2 mm. As FAA is more toxic to tumor-bearing animals than to those which are non-tumor bearing the effect of tumor conditioned medium on the cytotoxicity of FAA toward B10 cells was studied; no enhanced effect was seen. As FAA is only weakly cytotoxic in vitro to endothelial cells, and even less so to tumor cells, sublethal effects of FAA on endothelial cell function in vitro were studied. The permeability of monolayers of human unbilical vein endothelial cells (HUVEC) in vitro is transiently increased by FAA. Also, procoagulant activity of HUVEC is induced by FAA and this activity is further enhanced in the presence of a factor isolated from Meth-A tumor cells.     

Outcome of aneurysmal subarachnoid hemorrhage in patients 66 years of age and older

The outcome at three months after aneurysmal SAH in a group of older patients and a group of younger patients is compared. The patients were admitted within 72 hours of their SAH. Of 61 patients 66 years of age and older, comprising 13% of the whole patient group, 52% died, 12% remained dependent and 36% became independent. In the younger group, 55% had an independent outcome (p less than 0.01). In contrast to what we expected in the older patient group, not extracranial, but intracranial events (re-bleeds, infarcts, hydrocephalus) were by far the most frequent cause of deterioration.     

Does therapeutic reduction of diastolic blood pressure cause death from coronary heart disease?

Mortality data from 3350 patients who attended the Glasgow Blood Pressure Clinic between 1968 and the end of 1982 were used to examine the hypothesis that lowering diastolic blood pressure (DBP) below 85 mmHg causes death from coronary heart disease (CHD). Analysis of 257 coronary deaths in quintiles of treated DBP showed a significantly nonlinear relation, with the lowest mortality from CHD occurring in the middle quintile (91-98 mmHg). This finding persisted after adjustment for risk at entry, and was independent of sex and pre-existing CHD. In contrast, the relations between treated systolic blood pressure and death from CHD, and treated DBP and death from stroke were linear. For 2355 patients who were untreated at referral there was no relation between the change in DBP during treatment and death from CHD. In our view, however, these findings do not necessarily support the hypothesis that lowering of DBP below 85 mmHg with treatment causes death from CHD. Evidence for this is indirect and inconsistent, and should not, at present, be used as a basis for any change in treatment practice.     

Differences in triage thresholds for patients presenting with possible acute coronary syndromes: more than meets the eye.

BACKGROUND: Many studies have shown differences in cardiac care by racial/ethnic groups without accounting for institutional factors at the location of care. OBJECTIVE: Exploratory analysis of the effect of hospital funding status (public vs private) on emergency department (ED) triage decision making for patients with symptoms suggestive of acute coronary syndromes (ACSs) and on the likelihood of ED discharge for patients with confirmed ACS. STUDY DESIGN AND SETTING: Secondary analysis of data from a randomized controlled trial of 10,659 ED patients with possible ACS in five urban academic public and five private hospitals. The main outcome measures were the sensitivity and specificity of hospital admission for the presence of ACS at public and private hospitals and the adjusted odds of a patient with ACS not being hospitalized at public versus private hospitals. RESULTS: Of 10,659 ED patients, 1,856 had confirmed ACS. For patients with suspected ACS, triage decisions at private hospitals were considerably more sensitive (99 vs 96%; p<.001) but less specific (30 vs 48%; p<.001) than at public hospitals. The difference between hospital types persisted after adjustment for multiple patient-level and hospital-level characteristics. CONCLUSION: Significant differences in triage for patients with suspected ACS exist between public and private hospital EDs, even after adjustment for multiple patient demographic, clinical, and institutional factors. Further studies are needed to clarify the causes of the differences.     

Polymer Reaction Engineering VI Halifax,Canada May 21–26, 2006

Conference Reports: This section contains reports on topical conferences. Reports are usually written at the request of the editorial office, but unsolicited contributions are also welcome. Suggestions should be sent to the editorial office of the Macromolecular journals, preferably by E‐mail to macromol@wiley‐vch.de.     

Frame-based immobilization and targeting for stereotactic body radiation therapy.

Frame-based stereotactic body radiation therapy (SBRT), such as that conducted with Elekta's Stereotactic Body Frame, can provide an extra measure of precision in the delivery of radiation to extracranial targets, and facilitates secure patient immobilization. In this paper, we review the steps involved in optimal use of an extra-cranial immobilization device for SBRT treatments. Our approach to using frame-based SBRT consists of 4 steps: patient immobilization, tumor and organ motion control, treatment/planning correlation, and daily targeting with pretreatment quality assurance. Patient immobilization was achieved with the Vac-Loc bag, which uses styrofoam beads to conform to the patient's shape comfortably within the body frame. Organ and motion control was assessed under fluoroscopy and controlled via a frame-mounted abdominal pressure plate. The compression screw was tightened until the diaphragmatic excursion range was < 1 cm. Treatment planning was performed using the Philips Pinnacle 6.2b system. In this treatment process, a 20 to 30 noncoplanar beam arrangement was initially selected and an inverse beam weight optimization algorithm was applied. Those beams with low beam weights were removed, leaving a manageable number of beams for treatment delivery. After planning, daily targeting using computed tomography (CT) to verify x-, y-, and z-coordinates of the treatment isocenter were used as a measure of quality assurance. We found our daily setup variation typically averaged < 5 mm in all directions, which is comparable to other published studies on Stereotactic Body Frame. Treatment time ranged from 30 to 45 minutes. Results demonstrate that patients have experienced high rates of local control with acceptable rates of severe side effects - by virtue of the tightly constrained treatment fields. The body frame facilitated comfortable patient positioning and quality assurance checks of the tumor, in relation to another set of independent set of coordinates defined by the body frame fiducials. The ability to impose abdominal compression proved to be a simple way to reduce target and tissue motion. SBRT with Stereotactic Body Frame enables comfortable patient immobilization and facilitates repeated registering and re-registering of the patient to the frame. With the body frame, large-dose-per fraction treatment is possible for localized tumor deposits with the aim of attaining a more therapeutic result.