Intraoperative radiotherapy in the treatment of neuroblastoma: Report of a pilot study

Background: External beam radiotherapy in advanced neuroblastoma is limited by the volume of normal radiosensitive tissues included in the radiation field. Limitations to external radiation are the late effects to these tissues. Intraoperative radiotherapy (IORT) delivers a single high-radiation dose to a tumor while displacing normal tissues that would have been included in an external field. Standard external radiotherapy can still be done after boost IORT. Methods: Eight advanced-stage neuroblastoma patients who received IORT as part of their multimodality therapy were reviewed to identify the impact of IORT on operative time, complications, and tumor control in the treatment field. The IORT was accomplished by patient transport from the OR to the radiation therapy suite; these were separated by three floors. Results: IORT added 30–75 min to the operative procedure. Tumors in the resection/IORT fields showed no evidence of disease (one), stable tumor size (six), and tumor recurrence (one). Two complications were identified: a urinary fistula and CO₂ retention, which was detected and corrected before the IORT. Neither of these complications was related to the IORT. Two patients who had subsequent tumor resection after IORT demonstrated tumor differentiation to ganglioneuromatous tissue. Conclusions: IORT usually can be completed in less than an hour. No IORT-associated complications were identified. IORT along with maximal tumor resection, external radiation, and chemotherapy enhances local tumor control.Presented in part at the 47th Annual Symposium of The Society of Surgical Oncology, Houston, TX, March 17–20, 1994.     

Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension): effects of body weight and injection sites on pharmacokinetics

A new contraceptive option, medroxyprogesterone acetate (MPA) and estradiol cypionate (E2C) (MPA/E2C, Lunelle Monthly Contraceptive Injection), will soon be available for women in the US. This article reports the results of a US trial that assessed the effects of body weight and injection site on the pharmacokinetics of MPA, the progestin mediating contraceptive efficacy. This assessment was part of a nonrandomized, open-label, multicenter US study in healthy women receiving a monthly injection of MPA/E2C for 60 weeks. A total of 77 women (aged 18-47 years) at four centers participated in the pharmacokinetics assessment during the sixth or the seventh injection. For determination of serum MPA concentration-time profiles, blood samples were collected before the sixth and seventh injections (day 0) and on days 3, 7, 14, 21, and 28 after the sixth and seventh monthly administrations. For effects of injection site, MPA pharmacokinetics were compared at injection sites of the arm, hip, and leg. The pharmacokinetics of MPA, determined at the sixth and seventh injection, were not significantly affected by injection sites. The mean area under the curve (AUC0-28), however, was different between the arm and the leg injection sites; the difference was < 20%. More important, the average MPA trough concentrations (Cmin) at the fifth and sixth monthly injections were similar (range 0.42-0.51 ng/mL) for the three injection sites and well above the threshold levels of 0.10-0.20 ng/mL required to suppress ovulation. For effects of body mass index (BMI) on pharmacokinetics, women were stratified into three groups: thin/normal (BMI 18-28, n = 48), obese (BMI 29-38, n = 23), and highly obese (BMI > 38, n = 6). There were no significant differences in the pharmacokinetics of MPA among the three BMI categories. The only significant difference (p = 0.0387) was the AUC0-28 between BMI 18-28 and BMI 29-38. Because of the small sample size in the highly obese group, a reanalysis was performed by pooling subjects of the obese and highly obese groups. Results of the pooled statistical analysis remained the same. In summary, these results suggest that minor differences observed in the MPA pharmacokinetics--whether due to injection site or body weight or both--have no impact on the contraceptive efficacy of MPA/E2C, as trough concentrations (Cmin) are well above the threshold levels required to suppress ovulation. No dose adjustment is necessary based on body weight or injection site.     

Responsiveness of the hypothalamo-pituitary-interrenal axis in an amphibian (Bufo terrestris) exposed to coal combustion wastes

To assess the responsiveness of the interrenal axis to stress, we injected toads exposed to coal combustion wastes and toads from an unpolluted reference site with adrenocorticotropic hormone (ACTH), as well as the vehicle alone (saline). Initial circulating levels of corticosterone in toads captured at the polluted area were significantly higher than levels in toads from the reference site. Corticosterone levels in toads from the polluted site remained high even after 2 weeks of laboratory acclimation and injection with saline. The results may suggest disruption of hepatic enzymes responsible for the metabolic clearance of steroid hormones. Injection of toads from the polluted site with ACTH had no effect on plasma corticosterone levels, whereas a similar treatment of toads from the reference site stimulated a marked increase in corticosterone. Our study provides evidence that toads exposed to coal combustion wastes may be less efficient at responding to additional environmental stressors.     

Effects of different interval-training programs on cycling time-trial performance

PURPOSE: We have investigated the effect of varying the intensity of interval training on 40-km time-trial performance in 20 male endurance cyclists (peak oxygen uptake 4.8+/-0.6 L x min(-1), mean +/- SD). METHODS: Cyclists performed a 25-kJ sprint test, an incremental test to determine peak aerobic power (PP) and a simulated 40-km time-trial on a Kingcycle ergometer. They were then randomly assigned to one of five types of interval-training session: 12x30 s at 175% PP, 12x60 s at 100% PP, 12x2 min at 90% PP, 8x4 min at 85% PP, or 4x8 min at 80% PP. Cyclists completed 6 sessions over 3 wk, in addition to their usual aerobic base training. All laboratory tests were then repeated. RESULTS: Performances in the time trial were highly reliable when controlled for training effects (coefficient of variation = 1.1%). The percent improvement in the time trial was modeled as a polynomial function of the rank order of the intensity of the training intervals, a procedure validated by simulation. The cubic trend was strong and statistically significant (overall correlation = 0.70, P = 0.005) and predicted greatest enhancement for the intervals performed at 85% PP (2.8%, 95% CI = 4.3-1.3%) and at 175% PP (2.4%, 95% CI = 4.0-0.7%). Intervals performed at 100% PP and 80% PP did not produce statistically significant enhancements of performance. Quadratic and linear trends were weak or insubstantial. CONCLUSIONS: Interval training with work bouts close to race-pace enhance 1-h endurance performance; work bouts at much higher intensity also appear to improve performance, possibly by a different mechanism.     

Angioscopy-assisted aneurysm clipping.

OBJECTIVE: To test the concept that endovascular angioscopy can assist surgical intracranial aneurysm clipping by providing an endoluminal view of the aneurysm-parent vessel complex. METHODS: A carotid bifurcation aneurysm was surgically created in a dog at the lingual artery origin. A balloon catheter was inflated proximal to the aneurysm to block proximal blood flow and allow endoluminal visualization. A flexible angioscope connected to a video monitoring system and to a high-intensity light source was then advanced within the catheter lumen and positioned immediately distal to the catheter tip. The aneurysm neck was clipped, and the clip was repositioned several times along the neck, with or without distal parent vessel compromise. Each time, the endovascular image on the monitor was interpreted by an observer blinded to the position of the clip. Clip position and image interpretation were communicated independently to a third person, who analyzed the correlation between them. RESULTS: Angioscopy allowed clear visualization of the extent of aneurysm neck occlusion (complete, incomplete, residual "dog ear") after clip application, as well as the presence or absence of distal parent vessel compromise. Aneurysm neck configuration, size, presence of thrombus, and suture line definition were depicted. Critical structures external to the aneurysm-parent vessel complex were transilluminated by the high-intensity lamp. CONCLUSION: Although acknowledged as the treatment of choice for intracranial aneurysms, surgical exclusion can be accompanied by significant morbidity related to perforator occlusion, parent artery compromise, and/or persistent residual aneurysm. The availability of a device allowing visualization of an aneurysm from an endoluminal perspective theoretically could reduce the incidence of these complications. Angioscopy has the potential to become a useful adjunct during intracranial aneurysm clipping because it provides real-time endoluminal viewing of the aneurysm-distal parent vessel complex, which is sometimes obscured to the surgeon.