Patient perspectives on intraoperative awareness with explicit recall: report from a North American anaesthesia awareness registry.

BACKGROUND: Awareness during general anaesthesia is a source of concern for patients and anaesthetists, with potential for psychological and medicolegal sequelae. We used a registry to evaluate unintended awareness from the patient's perspective with an emphasis on their experiences and healthcare provider responses. METHODS: English-speaking subjects self-reported explicit recall of events during anaesthesia to the Anesthesia Awareness Registry of the ASA, completed a survey, and submitted copies of medical records. Anaesthesia awareness was defined as explicit recall of events during induction or maintenance of general anaesthesia. Patient experiences, satisfaction, and desired practitioner responses to explicit recall were based on survey responses. RESULTS: Most of the 68 respondents meeting inclusion criteria (75%) were dissatisfied with the manner in which their concerns were addressed by their healthcare providers, and many reported long-term harm. Half (51%) of respondents reported that neither the anaesthesia provider nor surgeon expressed concern about their experience. Few were offered an apology (10%) or referral for counseling (15%). Patient preferences for responses after an awareness episode included validation of their experience (37%), an explanation (28%), and discussion or follow-up to the episode (26%). CONCLUSIONS: Data from this registry confirm the serious impact of anaesthesia awareness for some patients, and suggest that patients need more systematic responses and follow-up by healthcare providers.

Alcohol consumption promotes insulin sensitivity without affecting body fat levels.

OBJECTIVE: Alcohol consumption promotes insulin sensitivity. In obesity, a decrease in body fat levels decreases the risk of developing insulin resistance; therefore, it is possible that alcohol improves insulin sensitivity by negatively affecting body fat. The aim of this study was to determine whether alcohol consumption promotes insulin sensitivity by reducing body fat levels in C57BL/6 male mice. METHODS: We examined the effects of alcohol consumption on insulin sensitivity in male mice with three different body weight (BW) phenotypes. The BWs were induced by feeding the mice a 30% calorie-restricted (CR) regimen, a low-fat (LF) diet and a high-fat (HF) diet. The mice had free access to water or 20% ethanol in the drinking water. To determine the effects of the three different BW phenotypes and of alcohol on glucose regulation and insulin sensitivity, we performed the insulin tolerance test (ITT) and glucose tolerance test (GTT) on the mice. The effects of the diets and alcohol on body composition, percent body fat (% BF), percent lean mass and bone mineral density (BMD) were determined by dual-energy X-ray absorptiometry (DEXA). RESULTS: Data show that mice with the highest body fat levels (HF) were insulin resistant and glucose intolerant. In contrast, mice with the lowest body fat levels (CR) were the most insulin sensitive and cleared the injected endogenous glucose the fastest. Results show that alcohol did not affect GTT in any of the BW phenotypes. However, alcohol consumption promoted insulin sensitivity in mice consuming both the LF and HF diets. Alcohol consumption increased insulin sensitivity without affecting body fat levels, as body fat levels were similar in mice consuming the LF or HF diets and drinking either water or alcohol. CONCLUSIONS: Alcohol consumption promotes insulin sensitivity without affecting body fat levels in mice consuming LF and HF diets.

Heat acclimation and HSP-72 expression in exercising humans.

The purpose of this research was to determine the effect of a 7-day heat acclimation protocol on HSP-72 expression in human skeletal muscle, and to examine the relationships between molecular and physiological markers of heat acclimation. Ten recreationally active male subjects (age = 23.3 +/- 2.81 yrs, VO(2peak) = 3.85 +/- 0.11 L . min (-1)) completed a 7-day heat acclimation protocol consisting of cycling at 75 % of VO(2peak) in a hot environment (39.5 degrees C, 27 % RH). Muscle biopsies were obtained on days 1 (HTT1) and 7 (HTT2) prior to, 6 h post, and 24 h postexercise to measure HSP-72 protein via SDS-PAGE and silver staining. Core rectal temperatures (T(C)), intramuscular temperatures (T(IM)), skin temperatures (T(SK)), heart rate (HR), oxygen uptake (VO(2)), sweat rate (SR), and plasma cortisol were measured. TC, HR, and plasma cortisol were significantly lower in HTT2 than HTT1 (p < or = 0.05). No significant differences were seen for VO(2), TIM, TSK, or SR when comparing HTT2 with HTT1 (p < or = 0.05). No significant time or day x time interactions were detected for HSP-72 expression (24.48 +/- 2.55 vs. 25.04 +/- 1.43 ng/microg protein for HTT1 and HTT2, respectively, p < or = 0.05). Evidence of heat acclimation was seen at the physiological level; however, no evidence of enhanced thermotolerance at the cellular level was indicated by HSP-72 expression.

Transforming growth factors induce markers of neoplasia in cultured adult rat bladder.

Transforming growth factors alpha and beta (TGF-alpha and TGF-beta) isolated from normal mouse kidney induced gross morphological changes in rat urothelial cells maintained in organ culture. These morphological effects are similar to those observed after long-term treatment of rat bladder organ cultures with the carcinogen N-methyl-N-nitrosourea (MNU) or the promoting agents sodium saccharin and sodium cyclamate. Cultures were treated continuously with 5-25 micrograms/ml of Bio-Gel P-30-purified TGF containing both TGF-alpha and TGF-beta between days 1 and 14 in culture, or with 5 micrograms/ml from days 28 to 42. Controls received 1-10 ng/ml epidermal growth factor (EGF) or control medium. Untreated controls retained a normal urothelium throughout the period of study. Mature superficial-type cells covered most of the surface and less mature forms appeared on the cut sides and damaged areas where cells followed the normal pattern of urothelial differentiation. EGF at 5 and 10 ng/ml caused necrosis of the entire urothelium but at 1 and 2 ng/ml had minimal effects on histology and scanning electron microscopical appearance up to 14 days in culture. Crude P-30-purified TGFs induced a series of dose-related changes from 4 days, which were maximal at 8 days and persisted or decreased between 8 and 14 days. These included hyperplasia, loss of epithelial polarity, hyperchromasia and elongation of basal cells between the overlying cell layers to reach the culture surface. Scanning electron microscopy showed the appearance at the culture surface of immature cells with gross surface abnormalities including large numbers of blebs, stubby microvilli and long pleomorphic microvilli. Immature cells on the sides of the culture and in damaged areas developed similar features. At crude TGF doses of 10 micrograms/ml many superficial cells were rounded, some became cystic and epithelial necrosis was observed. Cultures treated with h.p.l.c.-purified TGF-beta at 80 ng/ml in the presence of 2 ng/ml EGF showed similar effects to those treated with 5 micrograms/ml P-30-purified TGF. Fully differentiated cultures treated from 28 to 42 days with crude TGF, showed changes similar to those seen in early cultures. However, histological changes, particularly basal cell elongation were more widespread and there was an abnormal development of globular processes between the membrane ridges of mature superficial cells. Neither crude TGF nor EGF stimulated growth in soft agar of isolated epithelial cells from freshly killed rats or organ cultures pretreated for 7 days with EGF or TGF.(ABSTRACT TRUNCATED AT 400 WORDS)

Long-term organ culture of normal human bladder.

Normal adult human bladder obtained at cystoscopy has been maintained in long-term organ culture. Several media were tested for their ability to maintain viability and normal tissue morphology. The optimum medium was Ham's F-12 nutrient mixture, supplemented with 10% fetal calf serum, hydrocortisone (1 microgram/ml), and FeSO4, (0.45 microgram/ml). During the first 28 days in vitro, epithelial damage incurred at biopsy and during preparation of the cultures was repaired, and epithelialization of cut stromal surfaces occurred. A wave of cell proliferation was identified by [3H]thymidine autoradiography, 24-h labeling indices rising to a peak of up to 50% on the cut sides of the cultures between 7 and 21 days and falling to 0 to 5% by 21 to 28 days. The regenerating epithelium showed all the normal features of urothelial cell differentiation when examined by scanning and transmission electron microscopy. From 28 days, histology and scanning and transmission electron microscopy showed the cultured urothelium in most cultures to resemble closely that in the normal bladder in vivo, and in this mature state cultures were maintained for 100 days. Urothelium derived from certain patients, although showing normal surface maturation, developed enlarged intercellular spaces or intraepithelial mucin-containing acini. A study of the cytology of cells shed into the medium at different stages in culture showed that culture viability and epithelial differentiation could be monitored easily in long-term culture by this nondestructive means.

The phosphorylation of 5'-oligoadenylic acids by adenylate kinase and adenosine triphosphate.

1. Radioactivity was incorporated into 5'-O-phosphoryladenylyl-(3'-5')-adenosine (pApA) on incubation with adenylate kinase and [gamma-(32)P]ATP. The corresponding triadenylate and tetra-adenylate reacted more slowly. 2. Only oligoadenylate with a terminal 5'-phosphate served as the substrate. 3. The product formed from pApA was shown to behave like 5'-O-pyrophosphoryladenylyl-(3'-5')-adenosine (ppApA) on hydrolysis with alkaline phosphatase, potassium hydroxide and hydrochloric acid. 4. The characteristics of the reaction indicated that it was catalysed by adenylate kinase, but the rate of phosphate transfer from ATP to pApA was about 0.01% of that in the typical reaction with AMP. 5. The reverse reaction between ADP and ppApA occurred readily, but no additional phosphorylation of ppApA (to give pppApA) could be demonstrated.