Lumbar motoneuron fate in a mouse model of amyotrophic lateral sclerosis

Onuf's nucleus, a collection of motoneurons within the spinal cord, is often spared in the neurodegenerative disorder amyotrophic lateral sclerosis. To assess whether these cells survive in a rodent model of this disease, motoneurons were counted in the spinal nucleus of the bulbocavernosus (an homologous structure to Onuf's), as well as in two other cell groups at the same level of the spinal cord, the dorsolateral nucleus and the retrodorsolateral nucleus. In mice displaying signs of neurodegeneration, both the dorsolateral and retrodorsolateral nuclei displayed significant motoneuron loss compared to controls; this cell loss was particularly exaggerated in the retrodorsolateral nucleus of animals displaying a rapid disease progression. However, no significant decline in motoneuron number was observed in the spinal nucleus of the bulbocavernosus, and the perineal muscle bulbocavernosus, which is innervated by this nucleus, appeared to be unaffected. This was in stark contrast to the thigh muscles, which displayed significant atrophy. Overall, these data indicate that the spinal nucleus of the bulbocavernosus is spared from degeneration in an animal model of amyotrophic lateral sclerosis, paralleling observations in patients suffering from this disease. Further study of this resistance to motoneuron loss may provide useful insights into the pathophysiology of the degenerative process.     

A national 5-year follow-up of treatment outcomes for cocaine dependence

BACKGROUND: Long-term (5-year) outcomes of community treatment for cocaine dependence were examined in relation to problem severity at treatment entry and treatment exposure throughout the follow-up period. METHODS: Interviews were conducted at 1 and 5 years after treatment for 708 subjects (from 45 programs in 8 cities) who met DSM-III-R criteria for cocaine dependence when admitted to treatment in 1991-1993. Primary outcome measures included cocaine use and arrests. Self-reported cocaine use showed high overall agreement with urine (79% agreement) and hair (80% agreement) toxicology analyses. RESULTS: Weekly cocaine use was reported by 25% of the sample at 5 years, slightly higher than the 21% at 1 year. Similarly, 26% had cocaine detected in urine specimens at follow-up and 18% reported having been arrested. Poorer long-term outcomes were related to higher problem severity at treatment admission and low treatment exposure. CONCLUSIONS: The large decreases in cocaine use 1 year after treatment discharge were sustained during the 5-year follow-up. Severity of drug and psychosocial problems at intake was predictive of long-term outcomes and outcomes improved in direct relation to level of treatment exposure.     

Event and sideline management of sudden cardiac death

The increasing use of automated external defibrillators (AEDs), coupled with methods to improve cardiopulmonary resusitation and implementation of early defibrillation, have significantly improved survival from sudden cardiac death (SCD) in the prehospital setting. This article reviews the evidence and principles of management of SCD in the sports setting. It is noted that ventricular fibrillation is the most common arrhythmia causing SCD in athletes. When it occurs, survival is reduced by 7% to 10% per minute pending defibrillation. This statistic is true for athletes as well as nonathletes, and underscores the critical need for a rapid defibrillation response. Use of the AED in the sports setting and suggestions on whether to implement an AED program are reviewed. Despite increasing application of this technology, outcomes data on the use of AEDs in the sports arena are lacking, partly due to the relatively rare occurrence of SCD therein. New evidence on pharmacotherapy in SCD is also reviewed. Although drug administration in SCD is unlikely to be required in the sports setting, clinicians are updated on some of the newer considerations. Finally, selected articles from the recent literature on advanced cardiac life support are provided to guide the team physician in using the most current approach to the management of SCD.     

Hyperglycemia and reactive oxygen species mediate apoptosis in aortic endothelial cells through Janus kinase 2

The generation of reactive oxygen species (ROS) has been implicated in the perturbation of endothelial function and cell death. However, the specific signaling pathways which mediate and modifying this response have not been fully elucidated. Therefore, in this study we tested the hypothesis that activation of JAK2 is involved in the aortic endothelial cell (EC) response to ROS. When ECs were exposed to HG (25 mM) for 6 h or ROS (i.e., H(2)O(2) (100 microM)) for 1 h and returned to normal medium we found a decrease in cell density and morphologic signs of apoptosis. Furthermore, incubation of ECs with HG and H(2)O(2) also resulted in the tyrosine phosphorylation of JAK2. In addition, pretreatment of ECs with AG-490, an inhibitor of JAK2, prevented nuclear fragmentation, whereas inhibitors of Jun kinase (SP 600125), MAP kinase (PD 98059), Src kinase (PP2) or PI-3 kinase (wortmannin) were without effect. Finally, immunoblot analysis of caspase-3 and PARP cleavage confirmed a role for activation of JAK2 in both HG- or ROS-induced apoptosis, based on inhibition by either AG-490 or adenoviral transfection with a dominant-negative JAK2 mutant. In conclusion the activation of JAK2 plays a pivotal role in oxidant stress-induced commitment of ECs to apoptosis, based on studies with HG and H(2)O(2).     

Model-based detection of partially obstructed endotracheal tube

OBJECTIVES: A five-element lumped pulmonary model was developed to estimate respiratory mechanics automatically and noninvasively. The model was applied to diagnose obstructed endotracheal tube. Events like bronchospasm and stiff chest wall were also tested to determine the specificity of the diagnosis. Cases with positive end-expiratory pressure were also included in the analysis to see the effects of positive end-expiratory pressure on the model. DESIGN: Randomized controlled animal study. SETTING: University department of anesthesiology. SUBJECTS: Ten anesthetized, paralyzed, and mechanically ventilated mongrel dogs (19-45 kg) of either gender. INTERVENTIONS: Two levels of upper airway obstruction were induced in ten dogs by partially constricting the endotracheal tube. Acute bronchial constriction was produced in five dogs by injecting methacholine through a central venous catheter. In the same five dogs, the chest wall was stiffened by wrapping a pressure cuff around the chest. Positive end-expiratory pressure was also applied as a separate event in these five animals. MEASUREMENTS AND MAIN RESULTS: Airway pressure and flow were continuously recorded at the mouth. Model parameters were iteratively identified until the root mean square error between respiratory impedance (obtained from airway pressure and flow) and model-predicted impedance (calculated using Ohm's law) was minimum. The peak inspiratory pressure increased and the peak expiratory flow rate decreased with increasing levels of partial obstruction. The value of the model parameters R(1) and C(2) increased and C(1) decreased with partial obstructed endotracheal tube, whereas R(1) increased and L and C(2) decreased with bronchospasm. With stiff chest wall, R(2) increased and C(2) decreased. With positive end-expiratory pressure, the L parameter decreased and no significant change in other model parameters was observed. Obstructed endotracheal tube is indicated if R(1) increased > or =30%, C(1) decreased > or =10%, and C(2) increased > or =10% from baseline. The test results using 45 events, including control, three complications, and positive end-expiratory pressure, show that when the model is used to diagnose obstructed endotracheal tube, the method has a sensitivity of 90% and specificity of 97%. CONCLUSIONS: During an obstructed endotracheal tube, model parameters change such that the event can be diagnosed noninvasively, automatically, and accurately. The model differentiates between upper airway obstruction and complications like bronchospasm and stiff chest wall.     

Reproducibility of the heart rate variability responses to graded lower body negative pressure

The reproducibility of heart rate variability (HRV) measures during graded lower body negative pressure (LBNP) have not been studied in sufficient detail. Active college age men (n=14) underwent an orientation exposure and two trials of graded LBNP to presyncope or –100 mmHg, separated by 1 week. Heart rate, stroke volume (impedance cardiography), blood pressure (Finapres), and forearm blood flow were assessed, as was HRV in both time and frequency domains. The trial-to-trial responses to LBNP common to all subjects (LBNP–60 mmHg and at test termination) showed parallel changes, suggesting similar responses between both trials. Good reproducibility estimates were found for the resting HRV data (lowest: R=0.62 for low frequency/high frequency ratio; highest: R=0.94 for standard deviation of normal R-R intervals). During LBNP, reproducibility estimates varied but were generally similar to that seen at rest. At test termination, they were unacceptably low (R<0.41) for the HRV data assessed in the frequency domain and expressed in absolute units. LBNP tolerance was lower in the first trial [LBNP tolerance index: 404 (21) versus 437 (15) mmHg min^–1; P<0.05] but the intraclass correlation coefficient was high (R=0.87). These data suggest that (1) HRV responses to submaximal LBNP up to –60 mmHg are consistent across trials, (2) the considerable variability seen in the HRV parameters at maximal LBNP can be reduced by expressing these data in either the time domain or using normalized units in the frequency domain, and (3) cardiovascular responses to sub- and maximal LBNP are reproducible. Data are presented as mean (SEM) unless otherwise stated.     

Incidence of amyotrophic lateral sclerosis and of the parkinsonism-dementia complex of Guam, 1950-1989

Studies representing the accumulated information from the first 30 years of research effort on Guam (1950-1979) have demonstrated a varying degree of decline in the incidence of amyotrophic lateral sclerosis (ALS) and the parkinsonism-dementia complex (PDC) of Guam. Analysis with more complete information for the period 1980-1989 provides more valid estimates of the later patterns in the incidence of ALS and PDC and affords a more extensive assessment of trends over a 40-year period. The annual age-adjusted incidence of ALS was 7/100,000 and the annual age-adjusted incidence of PDC was 22/100,000 in 1989. The incidence was much higher for the period 1980-1989 than suggested in previous reports. These findings provide compelling evidence that this spectrum of neurodegenerative diseases continues to have a significant impact on the health of the Chamorro people of Guam.     

Mechanical exposure concepts using force as the agent

This paper presents a model that addresses mechanical exposure with regard to the development of musculoskeletal disorders, defines exposure concepts, unifies a variety of exposures, and includes the concept of human activity. When force is used as an agent, concepts related to the measurement, transformation, and interaction of the agent with tissues can be developed for use in epidemiologic exposure assessment and hazard assessment. The importance of tissue response in the exposure modeling process and in the creation of exposure indices is highlighted. Unfortunately, the response of tissue to forces of varying amplitudes and time variation patterns are largely unknown and thus reduce the possibility to develop optimal exposure assessment metrics. Although the paper argues that an exposure index at the tissue level may be the most powerful, considerations of resources and current knowledge make exposure indices based on external exposure or internal exposure preferable choices.     

Clinical evaluation of the Life Support for Trauma and Transport (LSTAT) platform

Introduction  

The Life Support for Trauma and Transport (LSTAT™) is a self-contained, stretcher-based miniature intensive care unit designed by the United States Army to provide care for critically injured patients during transport and in remote settings where resources are limited. The LSTAT contains conventional medical equipment that has been integrated into one platform and reduced in size to fit within the dimensional envelope of a North Atlantic Treaty Organization (NATO) stretcher. This study evaluated the clinical utility of the LSTAT in simulated and real clinical environments. Our hypothesis was that the LSTAT would be equivalent to conventional equipment in detecting and treating life-threatening problems.