A pilot survey of ventilated cancer patients' perspectives and recollections of early mobility in the intensive care unit.

PURPOSE: To determine the level of recall, satisfaction, and perceived benefits of early mobility (EM) among ventilated cancer patients after extubation in the intensive care unit (ICU). METHODS: A survey of patients' perceptions and recollections of EM was administered within 72 h of extubation. Data on recall of EM participation, activities achieved, adequacy of staffing and rest periods, strength to participate, activity level of difficulty, satisfaction with staff instructions, breathing management, and overall rating of the experience were analyzed. The Confusion Assessment Method for ICU (CAM-ICU) was used for delirium screening. RESULTS: Fifty-four patients comprised the study group. Nearly 90% reported satisfaction with instructions, staffing, rest periods, and breathing management during EM. Participants indicated that EM maintained their strength (67%) and gave them control over their recovery (61%); a minority felt optimistic (37%) and safe (22%). Patients who achieved more sessions and "out-of-bed" exercises had better recall of actual activities compared with those who exercised in bed. Overall, patients with CAM-ICU-positive results (33%) performed less physical and occupational therapy exercises. CONCLUSIONS: Ventilated cancer patients reported an overall positive EM experience, but factual memory impairment of EM activities was common. These findings highlight the needs and the importance of shaping strategies to deliver a more patient focused EM experience.

Inhibition of the complete set of mammalian secreted phospholipases A(2) by indole analogues: a structure-guided study.

Structure-guided design was employed in a search for potent and selective inhibitors of mammalian secreted phospholipases A(2) (sPLA(2)s). Using the X-ray structures of human groups IIA and X sPLA(2)s (hGIIA and hGX) as templates, homology structural models were made for the other human and mouse sPLA(2)s (hGIB, mGIB, mGIIA, mGIIC, hGIID, mGIID, hGIIE, mGIIE, hGIIF, mGIIF, hGV, mGV, and mGX). Me-Indoxam is a previously discovered indole analogue that binds tightly to many sPLA(2)s, and the X-ray structure of the hGX-Me-Indoxam complex was determined at a resolution of 2.0 A. Modeling suggests that the residues near the N(1)-substituent of Me-Indoxam vary significantly among the mammalian sPLA(2)s, and therefore a library of 83N(1)-variants was prepared by parallel synthesis. Several Me-Indoxam analogues bearing a 4-(2-oxy-ethanoic acid) side chain were potent inhibitors (IC(50) <0.05 microM) of hGIIA, mGIIA, mGIIC, hGIIE, mGIIE, hGV, and mGV, while they displayed intermediate potency (0.05-5 microM) against hGIB, mGIB, hGX, and mGX, and poorly inhibited (>5 microM) hGIID, mGIID, hGIIF, and mGIIF. Me-Indoxam analogues bearing a 5-(4-oxy-butanoic acid) side chain were generally less potent inhibitors. Although no compounds were found to be highly specific for a single human or mouse sPLA(2), combinations of Me-Indoxam analogues were discovered that could be used to distinguish the action of various sPLA(2)s in cellular events. For example, Me-Indoxam and compound 5 are approximately 5-fold more potent on hGIIA than on hGV, and compound 21 is 10-fold more potent on hGV versus hGIIA.