Long-term results of cyclosporine-steroid therapy in 131 non-matched cadaveric renal transplants.

One-hundred-and-twenty-eight recipients of 131 consecutive, non-matched cadaver renal allografts were treated with cyclosporine and steroids. They have been followed for 4 to 6 yr. Cumulative patient survival at 1-yr was 92.2% and at 6yr it is 77.8%. Cumulative graft survival at 1-yr was 79.4% and at 6 yr it is 50.0%. After the high-risk 1st yr, the rate of graft loss was even and similar to that reported after the 1st yr for grafts treated with azathioprine and steroids. This indicates that cyclosporine nephrotoxicity has not had an obvious adverse effect on the survival of chronically functioning grafts. The results were better with primary grafting versus retransplantation, but were not significantly influenced by age, diabetes mellitus, or a delayed switch in patients from cyclosporine to azathioprine. We have concluded that cyclosporine-steroid therapy is safe and effective for long-term use after cadaveric renal transplantation

Temperature compensation of aerobic capacity and performance in the Antarctic pteropod, \u3cem\u3eClione antarctica\u3c/em\u3e, compared with its northern congener, \u3cem\u3eC. limacina\u3c/em\u3e

In ectotherms living in cold waters, locomotory performance is constrained by a slower generation of the ATP that is needed to fuel muscle contraction. Both polar and temperate pteropods of the genus Clione, however, are able to swim continuously by flapping their parapodia (wings) at comparable frequencies at their respective habitat temperatures. Therefore, we expected polar species to have increased aerobic capacities in their wing muscles when measured at common temperatures. We investigated muscle and mitochondrial ultrastructure of Clione antarctica from the Southern Ocean (−1.8°C) and populations of a sister species, Clione limacina, from the Arctic (−0.5 to 3°C) and from the North Atlantic (10°C). We also measured oxygen consumption and the activity of the mitochondrial enzyme citrate synthase (CS) in isolated wings of the two species. The Antarctic species showed a substantial up-regulation of the density of oxidative muscle fibers, but at the expense of fast-twitch muscle fibers. Mitochondrial capacity was also substantially increased in the Antarctic species, with the cristae surface density (58.2±1.3μm2μm−3) more than twice that found in temperate species (34.3±0.8μm2μm−3). Arctic C. limacina was intermediate between these two populations (43.7±0.5μm2μm−3). The values for cold-adapted populations are on par with those found in high-performance vertebrates. As a result of oxidative muscle proliferation, CS activity was 4-fold greater in C. antarctica wings than in temperate C. limacina when measured at a common temperature (20°C). Oxygen consumption of isolated wing preparations was comparable in the two species when measured at their respective habitat temperatures. These findings indicate complete compensation of ATP generation in wing muscles across a 10°C temperature range, which supports similar wing-beat frequencies during locomotion at each species\u27 respective temperature. The elevated capacity in the wing muscles is reflected in the partial compensation of whole-animal oxygen consumption and feeding rates

Test-Retest Reliability of Standard Deviation of Lane Position as Assessed on a PC-Based Driving Simulator

Driving is an everyday activity that is commonly affected by neurologic disorders and medical treatments. A frequently used metric for assessing driving ability is the standard deviation of lane position (SDLP), or the amount that subjects “swerve” within their driving lane. This measurement has been used with individuals under the influence of alcohol, illicit drugs, and prescribed medications in both on-road and simulator studies. Although good test-retest reliability is critical if one is to measure change in individuals over time, there is surprisingly limited data regarding the test-retest reliability of SDLP. Objective. To examine the test-retest reliability of SDLP in subjects tested at (1) a 3-month retest interval (a time frame common to clinical trials), and (2) a year or longer retest interval (a time period over which one might track changes in neurologic patients. Methods. Group 1 completed retesting an average of 84 (s.d. = 8.1) days after their initial simulator assessment. Both HIV negative (HIV-; n = 16) and positive (HIV+; n = 13) subjects were included to explore short-term reliability in control and mildly ill patient groups. All HIV+ subjects were medically asymptomatic, and unlikely to experience HIV-related changes over this interval. Two HIV+ subjects were neuropsychologically (NP) impaired. Group 2 (n = 31), a different cohort, was retested an average of 19.8 (8.3) months after baseline. All subjects completed NP evaluations at baseline and follow-up, with NP status rated on a scale of 1 (above average) to 9 (severe impairment) by a clinician blinded to simulator performance. Twelve subjects (39%) were NP impaired. In order to examine reliability in a stable neurologic cohort, all subjects were selected because they remained at the same level of NP functioning at follow-up. SDLP was assessed in both groups using an interactive PC-based driving simulator that consisted of a monitor, steering wheel, and brake/accelerator pedals. Participants were required to maintain lane position while holding a constant speed (55 mph) and responding to divided attention tasks in the corner of the monitor. Group 2 completed an existing, standardized scenario (TOPS), while Group 1 completed a newly developed driving scenario. Both simulations lasted approximately 7 minutes. Results. Combined reliability for Group 1 was .74. Test-retest reliability was .68 for the HIVand .83 for the HIV+ subjects. For Group 2, SDLP was significantly correlated with NP functioning at baseline (r = .5, p = .005) and follow-up (r = .48, p = .006), with impaired subjects evidencing a higher SDLP than NP normal subjects at both baseline (mean of 1.9 vs 1.2; p = .006) and follow-up (1.7 vs 1.1, p = .01). Combined test-retest reliability for Group 2 was .86. The NP normal group had a test-retest reliability of .74; test-retest reliability for the NP impaired group was .87. Conclusions. SDLP is a reliable measure for periods ranging from months to years when assessed in cognitively stable subjects. As such, this may serve as a useful tool in tracking the effects of neurologic disorders and pharmacologic treatments on driving abilities

Driving Simulator Performance Across the Lifespan: A Preliminary Study

OBJECTIVES Normal aging is associated with decline in abilities that may put an individual at increased riskfor a crash. Older individuals may have slowed processing speed and motor responses, a reduceduseful field of view (Ball et al., 1988), and greater difficulty with mental rotation (Armstrong etal., 1998). Although collision rates increase with age (Transportation Research Board, 1988), ithas been argued that specific age-related functional impairments, and not age itself, put one atrisk (Ball & Owsley, 2003). The goal of this study was to examine the relationship betweenaging and performance on driving simulations assessing specific components of driving—accident avoidance, divided attention, and navigation—and the degree to which they predict onroaddriving performance.METHODSForty control drivers (age 22 to 84; \u3c 50 yo, n = 14; 50-70 yo, n = 13; and \u3e 70 yo, n = 13)completed 3 simulations and an on-road driving evaluation. Exclusion criteria includedneurologic confounds, substance use and psychiatric disorders, as well as abnormalneuropsychological performance (based upon demographically-corrected norms). Thesimulations were presented on a Pentium III PC computer using a 17” monitor at 1280 x 1024resolution, and running STISIM Drive version 2.0 software (Systems Technology, Inc.;Hawthorne, CA). Hardware included a steering wheel, turn signal, and brake/accelerator pedals.The simulations consisted of 1) Advanced Routine and Emergency Driving (ARED), a 15-minute route simulating city/country driving, in which drivers must obey traffic signs, pass cars,and respond to high-risk crash scenarios; 2) Virtual City (VC), in which drivers must navigate toand from a location in a 5 x 5 block simulated city, and 3) Divided Attention, in which driversare to maintain a constant speed and lane position while responding to divided attention tasks inthe corner of the monitor. Participants also completed a 35-minute on-road assessment. Lastly,participants were assessed on a battery of neuropsychological tests. Earlier versions of thesimulations were predictive of on-road driving performance in an HIV-infected cohort (Marcotteet al., 2004). RESULTSThe three groups performed similarly on ARED (crashes, speeding tickets), as well as on the VCtask when the map was oriented to the same direction as the participant. On the other hand, olderparticipants had significantly more difficulty navigating when their orientation on the map wasreversed (e.g., the \u3c 50 group took 1.2 blocks beyond optimum to return from the destination; the50-70 and \u3e 70 years old groups took approximately 7.5 blocks). The three groups performedsimilarly with respect to lane deviation on the Divided Attention task, but the older groups hadincreased variability in speed maintenance, and the oldest group failed to respond to a greaternumber of divided attention stimuli (\u3c 50 yo = .3 (.83), 50-70 yo = 1.0 (1.3), \u3e 70 yo = 3.6 (2.7)).Although only one participant failed the on-road drive (50-70 yo), the percent of driversconsidered marginal or worse increased with age (7% vs. 25% vs. 55%). In a logistic regression,the simulator variables that best discriminated safe vs. marginal on-road came from the DividedAttention task: the number of missed stimuli and speed deviation, both of which require an intactuseful field of view and the shifting of gaze away from the roadway. Age did not enter into amodel that included these variables.CONCLUSIONSIn this study of normal, healthy controls, older participants drove similarly to young-to-middleaged participants on a simulation that most closely approximated real driving. Consistent withcognitive declines seen in normal aging, older participants had greater difficulty on a taskrequiring navigating when map orientation was reversed (perhaps indicative of impairedegocentric spatial abilities), as well as on a measure of driving-related divided attention, witholder participants appearing to allocate more attention to the roadway at the cost of attending andresponding to peripheral cues. Although older drivers had more difficulty during the on-road test,these difficulties were a function of deficits in the ability to divide attention efficiently, ratherthan aging per se.REFERENCESArmstrong, C.L., & Cloud, B. (1998). The emergence of spatial rotation deficits in dementia andnormal aging. Neuropsychology, 12(2), 208-217.Ball, K.K., Beard, B.L., Roenker, D.L., Miller, R.L., & Griggs, D.S. (1988). Age and visualsearch: Expanding the useful field of view. J Opt Soc Am A, 5(12), 2210-2219.Ball, K., & Owsley, C. (2003). Driving competence: It\u27s not a matter of age. J Am Geriatr Soc,51(10), 1499-1501.Marcotte, T.D., Wolfson, T., Rosenthal, T.J., Heaton, R.K., Gonzalez, R., Ellis, R.J., et al.(2004). A multimodal assessment of driving performance in HIV infection. Neurology, 63(8),1417-1422.Transportation Research Board. (1988). Transportation in an Aging Society, Vol 1. Washington,D.C.: National Research Council

The Impact of Cognitive Deficits and Spasticity on Driving Simulator Performance in Multiple Sclerosis

Multiple sclerosis (MS) is a demyelinating disease that can result in numerous sequelae. Although spasticity and cognitive dysfunction are common in MS, few studies have examined the impact of both factors on driving abilities in persons with physical impairments. The present study assessed driving performance in control participants and MS patients with documented spasticity using two brief simulations designed to measure lane tracking (under high cognitive load) and car following behavior. Seventeen MS patients and 9 controls participated in the study. The MS cohort exhibited a broad range of cognitive functioning (normal to significant impairment) and disability (Expanded Disability Status Scale scores of 3.0 to 7.5). Eight of the MS patients had significant spasticity in their right knee based upon the Modified Ashworth Spasticity Scale. MS patients had greater difficulty than controls on the simulations, particularly on the car following task. MS participants also tended to drive at higher speeds than the control participants. Within the MS cohort, cognitive dysfunction was most strongly associated with lane tracking decrements, whereas the possible relationship between cognitive function and car following behavior was eclipsed by lower limb spasticity. Spastic individuals had greater difficulty mirroring speed changes in the lead car, and were approximately one second slower in responding to its accelerations and decelerations. The current simulations provide important data regarding the impact various MS sequelae may have on driving performance, and may ultimately lead to clinical recommendations regarding specific driving behaviors and their associated risks

Liver transplantation before 1 year of age

Since 1981, 20 infants younger than 1 year of age received 26 orthotopic liver transplants. Immunosuppression was with cyclosporine and corticosteroids. Thirteen (65%) of the reciplents were discharged from the hospital. To date, 12 (60%) of the 20 reciplents are surviving, with follow-up of 1 to 56 months (average 14 months). The 5-year acluarial survival is 53.8%. The allograft liver function in the majority of surviving infants is excellent. The predominant causes of mortality were primary nonfunction of the allograft (three patients) and sepsis (three). Major morbidity was caused by hepatic artery thrombosis (five patients), gastrointestinal complications (six), biliary tract complications (five), and bacterial and viral infections (13). Six patients underwent retransplantation; three of these six survived. Results could be improved by prevention of hepatic artery thrombosis, by decreasing the incidence of sepsis, and by procurement of more and better suited pediatric donors. © 1987 The C. V. Mosby Company

What Happened, and Why: Toward an Understanding of Human Error Based on Automated Analyses of Incident Reports

The objective of the Aviation System Monitoring and Modeling project of NASA's Aviation Safety and Security Program was to develop technologies to enable proactive management of safety risk, which entails identifying the precursor events and conditions that foreshadow most accidents. Information about what happened can be extracted from quantitative data sources, but the experiential account of the incident reporter is the best available source of information about why an incident happened. In Volume I, the concept of the Scenario was introduced as a pragmatic guide for identifying similarities of what happened based on the objective parameters that define the Context and the Outcome of a Scenario. In this Volume II, that study continues into the analyses of the free narratives to gain understanding as to why the incident occurred from the reporter s perspective. While this is just the first experiment, the results of our approach are encouraging and indicate that it will be possible to design an automated analysis process guided by the structure of the Scenario that can achieve the level of consistency and reliability of human analysis of narrative reports