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On 19 December 2008, a large portion of the S-shaped, steel-framed walkway under construction at the Atlanta Botanical Gardens suddenly collapsed during concrete placement operations. The approximately 575 ft long cable-stayed canopy bridge was designed to be supported by four masts along the curved spline segments and two opposing inclined columns at the transitional straight spline segments. At the time of collapse, the walkway structure was supported on temporary shoring tower frames and helical piles. A detailed study of movement and structural behavior was used to investigate the cause of collapse. Construction photos made it possible to compare erected locations of shoring tower frames and grillage members with their post-collapse locations and stacked configurations. Spline impact marks on the ground and shoring members below showed varying degrees of post-impact translation at points along the length of the collapsed walkway structure. Type and directionality of bolt failures at spline beam splices and abutments, and angles of inclination of shoring tower support piles above the ground surface were also considered. The movement displayed in these various elements pointed toward likely locations of collapse initiation among the numerous shoring towers. This study of movement allowed for a focused investigation to establish probable cause of the collapse.

Cisatracurium, one of 10 isomers of atracurium, undergoes pH and temperature-dependent Hofmann elimination in plasma and tissues. The clearance of cisatracurium due to Hofmann elimination and organ elimination was estimated by applying a nontraditional two-compartment pharmacokinetic model with elimination occurring from both compartments to plasma cisatracurium concentration-time data from 31 healthy adult surgical patients with normal renal and hepatic function. The elimination rate constant from the central compartment, intercompartmental rate constants, and the volume of the central compartment were obtained from the model fit. The elimination rate constant from the peripheral compartment could not be independently estimated in vivo and was therefore fixed to the rate of degradation of cisatracurium in human plasma (pH 7.4 and 37 degrees C) and held constant in the model. Total body clearance, Hofmann clearance, organ clearance, and the volume of distribution at steady-state were derived from the model parameter estimates. Renal clearance was calculated from cisatracurium urinary excretion data from 12 of the 31 patients. Clearance values (mean +/- SD) were 5.20 +/- 0.86, 4.00 +/- 1.04, 1.20 +/- 0.71, and 0.85 +/- 0.32 mL.min-1.kg-1 for total body clearance, Hofmann clearance, organ clearance, and renal clearance, respectively. Hofmann clearance accounted for 77% of total body clearance. Organ clearance was 23% of total body clearance. Renal clearance, a component of organ clearance, was 16% of total body clearance. The organ-independent nature of the elimination of cisatracurium was characterized by a relationship between steady-state volume of distribution and total body clearance. The half-life is an independent variable and is not dependent on the total body clearance nor the steady-state volume of distribution. Hofmann elimination is the predominant pathway for cisatracurium elimination in humans.

We compared both the time course of neuromuscular blockade and the cardiovascular side-effects of suxamethonium and mivacurium during halothane and nitrous oxide anaesthesia in infants 2-12 months and children 1-12 years of age. Equipotent doses of mivacurium and suxamethonium were studied; 2.2 x ED95 was used in four groups of infants and children, while 3.4 x ED95 was used in two groups of children. Onset of neuromuscular block in infants was not significantly faster with suxamethonium than with mivacurium (P = 0.2). In all infants given suxamethonium, intubating conditions were excellent, while, in 6/10 infants given mivacurium, intubating conditions were excellent. Onset of complete neuromuscular block in children was significantly faster with suxamethonium, 0.9 min compared with mivacurium, 1.4 min (P < or = 0.05). Increasing the dose of suxamethonium or mivacurium in children to 3.4 x ED95 did not change the onset of neuromuscular block. Recovery of neuromuscular transmission to 25% of initial twitch height (T25) in infants and children was significantly faster after suxamethonium than after mivacurium, at 2.5 and 6 min, respectively (P < or = 0.05). In children given 3.4 x ED95 of suxamethonium or mivacurium, recovery from neuromuscular block was almost identical with the dose of 2.2 x ED95, with spontaneous recovery to T25 prolonged by only 0.5 min. No infant or child had hypotension after the mivacurium bolus dose.

Aspiration pneumonitis is a severe complication of anesthesia. The objectives of this study were to determine if preoperative famotidine, a new histamine2-receptor antagonist, given by mouth either the evening before or the morning of elective surgery, reduced gastric residual volume and increased gastric pH in pediatric patients. Either famotidine or placebo (or both) were orally administered to 58 children (aged 2-17 years). The patients were randomly assigned to four groups: Famotidine-Famotidine, Placebo-Placebo, Placebo-Famotidine, and Famotidine-Placebo; subjects in the Famotidine-Famotidine group received two doses of famotidine (0.5 mg.kg-1 per dose), those in the Placebo-Placebo group, two doses of placebo, those in the Placebo-Famotidine and Famotidine-Placebo group, one dose of each by mouth. The Famotidine-Famotidine group received one dose of famotidine at 22:00 the evening before surgery and a second dose 60-90 min before the scheduled time of surgery. The Placebo-Placebo group received two doses of placebo at the same times as the Famotidine-Famotidine group. The Placebo-Famotidine group received a dose of placebo the night before surgery and a dose of famotidine the morning of surgery; the Famotidine-Placebo group received famotidine the night before surgery and placebo the morning of surgery. The administration of famotidine on the morning of surgery significantly increased gastric pH (4.8 vs. 1.3) in comparison with placebo, as did two doses of famotidine (6.6). Famotidine failed to reduce gastric residual volume significantly in any group. The administration of famotidine significantly reduced the number of pediatric patients considered at higher risk for aspiration pneumonitis, despite not decreasing gastric residual volume.

Objective: To evaluate the effect of an anti-smoking advertisement on young women's perceptions of smoking in movies and their intention to smoke. Subjects/setting: 2038 females aged 12–17 years attending cinemas in New South Wales, Australia. Design/intervention: Quasi-experimental study of patrons, who were surveyed after having viewed a movie at their local cinema. The control group was surveyed during week 1 and the intervention group, during week 2. Before seeing the movie in week 2, a 30 second anti-smoking advertisement was shown, which featured a well known female actor drawing attention to the prevalence of smoking in movies. Outcomes: Attitude of current smokers and non-smokers to smoking in the movies; intention of current smokers and non-smokers to be smoking in 12 months time. Results: Among non-smokers, 48.2% of the intervention subjects thought that the smoking in the movie they viewed was "not OK" compared with 28.3% of the control subjects (p < 0.0001). However, there was no difference among smokers in the intervention (26.4%) and control (16.9%) groups (p = 0.28). A higher percentage of current smokers in the intervention group indicated they were unlikely to smoke in 12 months time (47.8%) than smokers in the control condition (31.9%) (p = 0.03). For non-smokers, there was no difference in smoking intentions between conditions, with 95% saying they would be unlikely to be smoking in 12 months time. Conclusions: This "real world" study suggests that placing an anti-smoking advertisement before movies containing smoking scenes can help to "immunise" young women against the influences of film stars smoking.

Intraoperative fluid therapy may involve the initiation of fluid management or, alternatively, may be a continuation of ongoing fluid therapy. It can be as simple as replacing the deficits from the preoperative NPO status and providing maintenance fluids or as complex as correcting preoperative abnormal deficits, intraoperative translocated fluids, and variable blood loss, in addition to providing maintenance fluids.

We have determined the pharmacokinetics and duration of action of a bolus dose of mivacurium (0.15 mg kg-1) during isoflurane and nitrous oxide anaesthesia in nine patients with normal renal and liver function, nine patients undergoing cadaveric kidney transplantation and nine patients undergoing cadaveric liver transplantation. Total plasma concentrations of mivacurium were measured for 2.5 h after administration using a high-pressure liquid chromatographic assay. Plasma concentration vs time data for what were presumed to be the two active mivacurium isomers were analysed by a non-compartmental method based on statistical moments. Neuromuscular block was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The mean time to recovery of 25% neuromuscular transmission, T25, was greater in the patients with liver failure (57.2 min) than in control patients (18.7 min). The volume of distribution at steady rate (Vdss) was comparable in the three groups. Patients with impaired liver function had significantly longer mean residence time and smaller plasma clearance than did patients with renal failure or control patients. There were significant negative correlations between plasma cholinesterase activity and both T25 (r = 0.79) and mean residence time (r = 0.62).

We determined the pharmacokinetics and duration of action of a bolus dose of doxacurium (15 micrograms/kg) in 27 patients anesthetized with isoflurane and nitrous oxide. Nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures, nine were undergoing cadaveric kidney transplantation because of end-stage renal disease, and nine were undergoing cadaveric liver transplantation because of end-stage hepatocellular disease. Plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train-of-four response. The pharmacokinetic variables were (normal vs hepatic failure vs renal failure, respectively): volume of distribution at steady state (220 +/- 110 vs 290 +/- 60 vs 270 +/- 130 mL/kg [mean +/- SD]), plasma clearance (2.7 +/- 1.6 vs 2.3 +/- 0.4 vs 1.2 +/- 0.7 mL.kg-1.min-1), mean residence time (95.2 +/- 57 vs 129.4 +/- 30 vs 270 +/- 210 min), and elimination half-life (99 +/- 54 vs 115 +/- 31 vs 221 +/- 156 min). Plasma clearance and mean residence time differed significantly between patients with renal failure and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Parameterizations in high-end climate models can be evaluated with observed climate and meteorological data. Often this evaluation is achieved by averaging measured quantities over time and space to match the spatial and temporal resolution of a gridded climate model without any regard for the statistical errors in doing so. We present a statistical method to interpolate sparsely located surface measurements into a uniform spatial grid representative of global and regional models of the atmosphere and climate. This method provides estimates of mean values over the entire domain containing the measurement sites as well as the uncertainty in the estimated quantities at the grid locations through multiple simulations to create 'data ensembles.' We demonstrate this method using measurements of surface sensible heat flux over the southern Great Plains region gathered through the Department of Energy's Atmospheric Radiation Measurement (ARM) program. Application to the numerous other climate variables measured through the ARM program and the development of a software tool to streamline data management and implementation of the statistical models is also discussed.

2062 Background: Preclinical studies demonstrate that irinotecan, approved for I.V. administration, is most effective when administered at frequent, low doses. This administration schedule would be most practical if irinotecan were administered orally. However, the oral availability of irinotecan is limited. Gefitinib can alter the oral bioavailability of irinotecan through inhibition of gut transporters (ABCG2) that prevent intestinal absorption. Thus, we evaluated a potential method for giving irinotecan at low doses on a protracted schedule by administering orally with gefitinib. Additionally, we hypothesized that the pharmacokinetics of irinotecan may differ in older versus younger adult mice. Plasma levels of SN-38 were measured and compared in old and young Balb/c mice given oral irinotecan alone or with gefitinib. Methods: Adult (2 months old) and older, retired breeder (10 months old) Balb/c mice were orally administered irinotecan at 10 mg/kg, 20 mg/kg or 40 mg/kg either alone (control) or with 30 mg/kg PO gefitinib daily for 5 days. On the fifth day, the mice were sacrificed approximately 4–6 hours after administering drugs. Plasma was collected and SN-38 levels determined by HPLC. Results: Nearly all mice receiving irinotecan with gefitinib had a 3 fold or more increase in the level of SN-38 in the plasma as compared to the mice receiving irinotecan alone. The older mice had a more dramatic increase. Conclusions: The plasma levels of SN-38 were consistently elevated in mice treated with oral gefitinib and irinotecan when compared to mice treated with irinotecan only. The more pronounced increase in SN-38 levels seen in the older mice may be due to changes in drug elimination with aging. The results indicate that oral irinotecan can be given in the presence of gefitinib resulting in higher levels of SN-38 in the plasma of young and older mice. Combination treatment allows easier titration of irinotecan in protracted dosing protocols evaluating efficacy and toxicity in older mice, and ultimately, humans. [Table: see text] No significant financial relationships to disclose.

We studied a cat model simulating laudanosine accumulation in the "anephric" patient. Cardiovascular effects were seen only with the bolus doses of laudanosine 2 mg kg-1, and at plasma laudanosine concentrations unlikely to be achieved clinically. Similarly, EEG and power spectra analysis showed no evidence of epileptiform activity at all plasma laudanosine concentrations achieved. The non-specific EEG/power spectra changes observed may reflect a direct CNS activity with neurodepression, since laudanosine was shown by its presence in CSF to cross the blood-brain barrier. These EEG changes were observed at plasma concentrations eight to 10 times those observed in humans during infusion of atracurium. Thus, laudanosine accumulation and related CNS or cardiovascular toxicity seem unlikely following atracurium administration in the anephric patient.

The pharmacokinetics of atracurium were studied in infants and children anaesthetized with isoflurane and nitrous oxide in oxygen. There were no significant differences in volume of distribution (area) (139 v. 152 ml kg-1), clearance (5.1 v. 5.3 ml kg-1 min-1), T1/2 alpha (2.1 v. 2.0 min), or T1/2 beta (19.1 v. 20.3 min) between children with normal hepatic and renal function and those with moderately impaired hepatic function presenting for hepatic transplantation. There were significant differences in volume of distribution (area) (176 v. 139 ml kg-1) and in clearance of atracurium (9.1 v. 5.1 ml kg-1 min-1) between infants and children with normal excretory function. In infants the clearance of atracurium in ml m-2 min-1 (153 v. 133) tended to be greater and the T1/2 alpha and T1/2 beta tended to be shorter (1.0 v. 2.0 and 13.6 v. 19.1) than in children with normal excretory function; however, these trends did not reach statistical significance. Plasma laudanosine concentration was around 100 ng ml-1 greater in patients with liver disease than in normal children from 15-45 min following a bolus of atracurium 0.5 mg kg-1.

The pharmacodynamics of neuromuscular transmission, following blockade by a single i.v. dose of tubocurarine (dtc) in humans, were simulated from experimental serum dtc concentration versus time data and serum dtc concentration versus percentage recovery data. Good agreement was obtained between the simulated and experimental time course of recovery at five different therapeutic doses. The initial apparent volume of distribution (Vapp) of dtc was approximately the same as the serum volume and appeared to increase with the size of the dose. These results were consistent with the suggestion that a greater fraction of the dose of dtc was distributed in non-vascular spaces or bound to tissue at larger doses. A pharmacodynamic working model using an average Vapp of 2848 ml simulated times up to 40% recovery within 15-20% error for doses of dtc of 0.30 mg/kg or less.

The purpose of this study was to determine: (a) whether a difference in the inspired median effective dose (ED,50) for halothane exists between 15-day-old and 30-day-old rats, (b) whether halothane concentrations in the brain and heart, associated with anesthesia and cardiac failure, differ as a function of age, and (c) the cardiovascular index for halothane (i.e., the ratio of the halothane concentration in the heart at cardiac failure and the halothane concentration in the heart at anesthesia) for the two groups of young rats. Mean EDI50 of halothane was determined in 15-, 30-, and 60-day-old rats by testing for movement and lack of movement (anesthesia) in response to tail clamping using the nonparametric method of Waud. Tissue concentrations of halothane (mg/100 g) were measured by gas chromatography at the end points of anesthesia and cardiovascular failure. Water content in the brain (as a function of age) was determined in separate groups of 15-, 30-, and 60-day-old rats. The ED,50 for halothane was greater in the 15-day-old rats than in the 30-day-old rats (p

With the publication of the Pendery et al. follow-up of the Sobells' experimental studies of controlled drinking, serious questions about the relationship of paraprofessionals (i.e., craftsmen) and professionals in the improvement of alcoholism treatment have been raised. The present analysis reexamines the original published data of the controlled drinking studies in light of the Pendery et al. follow-up and draws the conclusion that readers can find support for both the success and failure of the controlled drinking by examining only the Sobells' data. On this basis, a more phenomenological view of alcoholism and alcoholism treatment is suggested as a way out of the schism between the craftsman and the professional, both of whom operate from within a linear, cause-effect mode of thinking.

In order to better understand the mechanism of hypotension and bradycardia in newborn infants under halothane anesthesia, we studied the changes in the four determinants of cardiac output in newborn piglets given 0.5 and 1% end tidal halothane. Cardiac index (CI) was measured by thermodilution. Preload was estimated from the left ventricular diastolic dimension determined by echocardiography and from the left ventricular end-diastolic pressure. Total peripheral resistance index was calculated to assess afterload. Contractility was estimated from left ventricular peak dP/dT, and from left ventricular shortening fraction and mean rate of circumferential fiber shortening determined by echocardiography. All indices of contractility decreased to approximately 50% of baseline values during administration of 1% halothane, whereas heart rate (HR) was reduced to 74% of baseline. Preload and afterload did not change significantly. Mean arterial pressure (MAP) and CI decreased to 67% and 74% of control values, respectively. Smaller, proportional reductions in all variables occurred when 0.5% halothane was administered. Control values of MAP were the only measurements significantly related to piglet age. When five additional animals underwent atrial pacing at the control HR during 1% halothane anesthesia, MAP and CI decreased to 66 and 71% of control values, respectively. dP/dT/DP40, a dP/dT point measurement independent of preload and afterload changes, decreased to 49% of control during pacing. Therefore, the major effect of halothane in newborn piglets is its potent negative inotropic action, not peripheral vasodilation or bradycardia.