[SLEEP OF ELITE YOUNG ATHLETE AT THE ACADEMY FOR SPORT EXCELLENCE AT THE WINGATE INSTITUTE].

INTRODUCTION: Sleep duration and quality have a critical role in cognitive and athletic performances. A relationship was demonstrated between sleep deprivation, reduced performance and elevated injury risk. The recommended sleep duration for teenagers is at least 9 hours a day but most sleep less. AIM: To estimate sleep duration among elite adolescent athletes at the Academy for Sport Excellence at the Wingate Institute, by quantifying the changes after joining the academy and the relation to school performances and the usage of medical services. METHODS: Data from medical records, including sleep screening questionnaires and a number of the athletes' medical appointments were analyzed. RESULTS: Athletes reported that sleep duration was less than recommended before joining the academy. After joining the academy the average sleep duration decreased (7.37 vs 7.7 hours, P = 0.05) and daytime sleepiness was elevated (13/24 v 11/24 Epworth-Sleepiness-Scale (ESS), P = 0.002). Correlations between changes in sleep duration and changes in school achievements before and after joining the academy were demonstrated (P = 0.027). No correlation was found between sleep duration at the academy and usage of medical services. CONCLUSIONS: Elite adolescent athletes do not sleep enough and are tired during the day. Reduction in sleep duration and elevation in sleepiness were observed with the transition to practice, study and life at the Academy for Sport Excellence. DISCUSSION: In accordance with previous studies, our findings showed elite young athletes are in a state of continuous sleep deprivation that interferes with their school achievements. Further research is needed to evaluate the importance of sleep duration and quality in performance for the health of young athletes.

Validation of ECG-derived sleep architecture and ventilation in sleep apnea and chronic fatigue syndrome.

PURPOSE: Newly developed algorithms putatively derive measures of sleep, wakefulness, and respiratory disturbance index (RDI) through detailed analysis of heart rate variability (HRV). Here, we establish levels of agreement for one such algorithm through comparative analysis of HRV-derived values of sleep-wake architecture and RDI with those calculated from manually scored polysomnographic (PSG) recordings. METHODS: Archived PSG data collected from 234 subjects who participated in a 3-day, 2-night study characterizing polysomnographic traits of chronic fatigue syndrome were scored manually. The electrocardiogram and pulse oximetry channels were scored separately with a novel scoring algorithm to derive values for wakefulness, sleep architecture, and RDI. RESULTS: Four hundred fifty-four whole-night PSG recordings were acquired, of which, 410 were technically acceptable. Comparative analyses demonstrated no difference for total minutes of sleep, wake, NREM, REM, nor sleep efficiency generated through manual scoring with those derived through HRV analyses. When NREM sleep was further partitioned into slow-wave sleep (stages 3-4) and light sleep (stages 1-2), values calculated through manual scoring differed significantly from those derived through HRV analyses. Levels of agreement between RDIs derived through the two methods revealed an R = 0.89. The Bland-Altman approach for determining levels of agreement between RDIs generated through manual scoring with those derived through HRV analysis revealed a mean difference of -0.7 +/- 8.8 (mean +/- two standard deviations). CONCLUSION: We found no difference between values of wakefulness, sleep, NREM, REM sleep, and RDI calculated from manually scored PSG recordings with those derived through analyses of HRV.

Phase I study of prolonged infusion Bryostatin-1 in patients with advanced malignancies.

PURPOSE: Bryostatin-1 is a compound known to inhibit protein kinase C expression. Clinical trials have focused on administration schedules ranging from 1 hour to 72 hour infusions. Preclinical data suggest that the down regulation of the target PKC occurs only as long as the drug is being infused. Therefore we performed a phase 1 clinical trial to determine the safety and recommended dose of prolonged infusion Bryostatin-1. EXPERIMENTAL DESIGN: Patients with advanced metastatic cancer were enrolled in this traditional phase 1 clinical trial utilizing prolonged infusion Bryostatin-1. The administration of Bryostatin-1 was initially begun at 96 hours and extended to 14 days. Doses were escalated using the 96 hour infusion time and then duration of infusion was increased. All patients underwent extensive sampling for determination of PKC levels as well as other key biologic end points. The determination of maximum tolerated dose and recommended phase two dose were based on toxicity. RESULTS: 38 patients were enrolled in the study. The recommended phase two doses were 24 mcg/m2 over five days, 16 mcg/m2 over six days and 8 mcg/m2 over 14 days. At the higher dose levels we demonstrated consistent down regulation of PKC-alpha. This was not observed at the low dose level. Toxicities were limited to myalgias and fatigue and were dose-related. The results of downstream signaling effects were less clear. MMP expression was not altered by treatment with Bryostatin-1. Only limited evidence for alterations in PKC activity as measured by expression of phosphorylated MAPK was observed. No objective responses were observed with five patients having prolonged stabilization of disease. CONCLUSIONS: Bryostatin-1 is safely administered over prolonged infusion schedules. There appears to be a dose response for PKC inhibition. Bryostatin-1 is a complicated compound as is the target PKC and its related signaling pathways. There is only limited clinical activity with this compound as a single agent; future studies should focus on combinations with other cytotoxics or targeted therapies.

A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer.

This phase II study was designed to characterize the clinical activity of ISIS 3521 in patients with metastatic colorectal cancer (CRC). Sixteen patients with pretreated or refractory CRC were treated with ISIS 3521. Eleven patients were given a dose of 2.0 mg/kg per day, and 5 patients received 3.0 mg/kg per day given over 21 days followed by a 7-day rest period. Patients continued with study until evidence of disease progression or unacceptable toxicity was detected. Patients underwent baseline tumor biopsies followed by a second biopsy during the last week of the first 21-day infusion. All 16 patients underwent baseline tumor biopsies, and 12 of the 16 patients underwent on-study tumor biopsies. No evidence of tumor response was observed. One patient had stable disease after 2 cycles and remained on for 1 additional cycle only to demonstrate progression of disease at that time. No dose-limiting or other significant toxicities were observed at both dosages, which could not be explained by progression of disease. Fatigue was common in all patients treated but was not dose limiting, and there was no evidence of coagulopathy. Analysis of the tumor biopsies obtained from the 11 evaluable samples showed marked uptake of ISIS 3521 in the normal liver parenchyma. However, there was minimal uptake within the tumor cells. In addition, no evidence of any alteration in protein kinase C-a within the tumors or any downstream effects leading to apoptosis were observed. ISIS 3521 demonstrated no clinical activity or target modulation in refractory metastatic CRC.