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 beta adrenergic blockade influence the prognostic implications of post-myocardial infarction exercise testing?

The influence of beta blockade on the ability of ST depression, during pre-discharge exercise testing, to predict coronary anatomy and subsequent complications was studied in 300 consecutive post-infarct patients, 125 of whom underwent cardiac catheterisation. At the time of exercise 62 patients were taking a beta blocker. The exercise test had a higher sensitivity in predicting multivessel disease in patients who were not taking beta blockers than in patients who were (95% v 76%). beta Blockade did not, however, influence the ability of the test to identify patients at risk of subsequent cardiac events (sensitivity 84% and 85% respectively). These results suggest that it is not necessary to stop treatment with beta blockers before predischarge exercise testing of patients who have had an acute myocardial infarction.     

Post-treatment sarcoma in breast cancer patients

Background: Many patients treated for breast cancer with radiotherapy will survive their disease and be at risk for treatment-related sarcoma for many years. Methods: In order to identify patients with post-treatment sarcoma and define this disease, we examined the records of 99 patients treated for sarcoma with a history of antecedent breast carcinoma. Of these patients, 51 were felt to have a sarcoma unrelated to breast cancer treatment and 48 were felt to have a treatment-related sarcoma (secondary to lymphedema and/or radiation). Results: Lymphangiosarcoma of the extremity was the most common histologic subtype of post-treatment sarcoma, accounting for 22 of 48 cases (46%). Twenty-six patients (54%) developed nonlymphangiosarcoma post-treatment sarcoma; all of these were radiation-associated sarcomas. The median latency interval between the diagnosis of breast cancer and the development of sarcoma was 11 years (range 4–44) and was not different between the two groups. However, patients with nonlymphangiosarcoma were significantly younger when diagnosed with breast cancer than were those with lymphangiosarcoma of the extremity (median 43 vs. 51 years, p<0.001). The survival of all 48 patients was poor: 5-year survival was 29%. Five-year survival of patients with other types of post-treatment sarcoma was just as poor as those with lymphangiosarcoma of the extremity (30% vs. 28%, p=0.98). Conclusions: Patients who develop sarcoma after treatment for breast cancer have a poor prognosis whether it occurs as Stewart-Treves syndrome or other types of post-treatment sarcoma. Younger patients may be at higher risk than are older patients for the development of nonlymphangiosarcoma post-treatment sarcoma.Presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, March 18–21, 1993.     

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.     

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.