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Biomedical subjects

J S Crowley

Publications and source records attributed to J S Crowley.

At least 19 recordsLinked to original sources
PubMed1996

Melatonin efficacy in aviation missions requiring rapid deployment and night operations.

BACKGROUND: The rapid deployment of Army aviation personnel across time zones, combined with missions beginning immediately upon arrival, results in desynchronization of physiological and cognitive performance rhythms. Implementation of effective countermeasures enhances safety, health, well-being, and mission completion. The naturally occurring hormone melatonin has been suggested as an effective counter measure for jet lag and shift lag because of its influence on the human circadian timing system and its hypnotic properties. METHODS: The efficacy of melatonin (10 mg) in maintaining stable sleep/wake cycles of Army aircrews was tested during a training mission involving rapid deployment to the Middle East and night operations. Cognitive performance was tested before and after travel; activity rhythms were recorded continuously for 13 d. RESULTS: Melatonin treatment advanced both bedtimes and rise times (2-3 h) and maintained sleep durations between 7-8 h. Placebo treatment was mostly associated with longer advances in rise times than bedtimes resulting in shorter sleep durations (5-7 h). Upon awakening, the melatonin group exhibited significantly fewer errors (mean: 7.45) than the placebo group (mean: 14.50) in a dual-task vigilance test. CONCLUSION: Melatonin can be a useful treatment for the prevention of sleep disruptions and cognitive degradation, even in uncontrolled sleeping environments characteristic of military deployments.

Adult↗
PubMed1995

Increased human immunodeficiency virus (HIV) type 1 DNA content and quinolinic acid concentration in brain tissues from patients with HIV encephalopathy.

Levels of human immunodeficiency virus type 1 (HIV-1) DNA and quinolinic acid were examined in areas of the central nervous system (CNS) and lymphoid organs (LN) from 5 AIDS patients with no clinically apparent CNS compromise (group I), 7 with CNS opportunistic diseases (group II), and 8 with HIV encephalopathy (group III). The brains from patients with HIV encephalopathy not only contained higher levels of HIV-1 DNA (cerebrum, P < .01; cerebellum, P < .05) as assessed by quantitative polymerase chain reaction but also showed a higher rate of viral pol region mutations suggestive of zidovudine or didanosine resistance than brains from patients in group I or II (P < .01). CNS quinolinic acid concentrations were significantly higher in group II and III patients than in group I (P = .03), even though quinolinic acid levels in LN were comparable among the 3 groups. These data suggest that CNS inflammatory changes associated with HIV encephalopathy may be triggered by a local productive HIV-1 infection within the CNS.

AIDS Dementia Complex↗
PubMed1995

Sustaining helicopter pilot performance with Dexedrine during periods of sleep deprivation.

BACKGROUND: Around-the-clock operations often are mandated in combat, but while aircraft can function effectively throughout continuous 24-hour periods, aviators often cannot because of sleep loss. An efficacious countermeasure in sustained operations may be the administration of dextroamphetamine (Dexedrine). HYPOTHESIS: Dexedrine will effectively prevent many of the performance problems associated with sleep deprivation in helicopter pilots. METHODS: A placebo-controlled, double blind study was conducted. Six U.S. Army helicopter pilots completed five flights in a UH-60 simulator while their performance was evaluated. Immediately following each flight, data were collected on electroencephalographic (EEG) activity and subjective mood ratings. Testing sessions occurred at 0100, 0500, 0900, 1300, and 1700. One hour prior to each of the first three flights on drug-administration days, the aviators were given 10 mg of Dexedrine or placebo. RESULTS: Dexedrine, in comparison to placebo, improved aviator simulator control on descents, straight-and-levels, standard-rate turns, and a left-descending turn. Performance was facilitated most noticeably at 0500, 0900, and 1700 (after 22, 26, and 34 hours of continuous wakefulness). EEG and mood data showed that alertness was sustained significantly by Dexedrine--there was reduced slow-wave EEG activity and improved rating of vigor and fatigue. No adverse behavioral or physiological effects were observed. CONCLUSIONS: Dexedrine appears to be effective for sustaining helicopter pilot performance during short periods of sleep loss without producing adverse side effects.

Adult↗
PubMed1993

A mechanism for increased quinolinic acid formation following acute systemic immune stimulation.

Mechanisms for increased levels of quinolinic acid (QUIN) following systemic immune stimulation were investigated. In gerbils, systemic administration of pokeweed mitogen (PWM) increased plasma and cerebrospinal fluid QUIN levels, while plasma kynurenic acid levels were decreased and cerebrospinal fluid kynurenic acid levels were unchanged. PWM also increased the QUIN concentrations of brain and systemic tissues. In slices of spleen, lung, liver, duodenum, and kidney, PWM caused marked increases in [13C6]QUIN formation from L-[13C6]tryptophan (but not from [13C6]anthranilic acid). PWM also increased QUIN excretion in the urine and enhanced the formation and excretion of [13C6]QUIN following an intraperitoneal injection of L-[13C6]tryptophan. Indoleamine-2,3-dioxygenase activity was increased in the brain, kidney, lung, spleen, and duodenum while hepatic L-tryptophan-2,3-dioxygenase activity was reduced, data consistent with in vitro L-kynurenine formation from L-tryptophan. Kynurenine-3-hydroxylase activity was increased in the duodenum, lung, and spleen, but not in the brain, kidney, or liver. Kynureninase activity was increased in the brain, lung, and duodenum, but not in the spleen, kidney, or liver. 3-Hydroxyanthranilate-3,4-dioxygenase activity was unchanged in the brain, lung, and liver. No change in kynurenine aminotransferase activity was observed in the brain or lung, while liver kynurenine aminotransferase activity was reduced. We conclude that increased activities of kynurenine pathway enzymes in various tissues following systemic immune stimulation, in conjunction with macrophage infiltration of the affected tissue, provide a mechanism to account for increased concentrations of QUIN.

Animals↗
PubMed1993

4-Chloro-3-hydroxyanthranilate, 6-chlorotryptophan and norharmane attenuate quinolinic acid formation by interferon-gamma-stimulated monocytes (THP-1 cells).

Accumulation of quinolinic acid and L-kynurenine occurs in the brain and/or blood following immune activation, and may derive from L-tryptophan following induction of indoleamine 2,3-dioxygenase and other kynurenine-pathway enzymes. In the present study a survey of various cell lines derived from either brain or systemic tissues showed that, while all cells examined responded to interferon-gamma by increased conversion of L-[13C6]tryptophan into L-kynurenine (human: B-lymphocytes, neuroblastoma, glioblastoma, lung, liver, kidney; rat brain: microglia, astrocytes and oligodendrocytes), only macrophage-derived cells (peripheral-blood mononuclear cells; THP-1, U-937) and certain liver cells (SKHep1) synthesized [13C6]quinolinic acid. Tumour necrosis factor-alpha enhanced the effects of interferon-gamma in THP-1 cells. Norharmane, 6-chloro-DL-tryptophan and 4-chloro-3-hydroxyanthranilate attenuated quinolinic acid formation by THP-1 cells with IC50 values of 51 microM, 58 microM and 0.11 microM respectively. Norharmane and 6-chloro-DL-tryptophan attenuated L-kynurenine formation with IC50 values of 43 microM and 51 microM respectively, whereas 4-chloro-3-hydroxyanthranilate had no effect on L-kynurenine accumulation. The reductions in L-kynurenine and quinolinic acid formation are consistent with the reports that norharmane is an inhibitor of indoleamine 2,3-dioxygenase, 6-chloro-DL-tryptophan is metabolized through the kynurenine pathway, and 4-chloro-3-hydroxyanthranilate is an inhibitor of 3-hydroxyanthranilate 3,4-dioxygenase. These results suggest that many tissues may contribute to the production of L-kynurenine following indoleamine 2,3-dioxygenase induction and immune activation. Quinolinic acid may be directly synthesized from L-tryptophan in both macrophages and certain types of liver cells, although uptake of quinolinic acid precursors from blood may contribute to quinolinic acid synthesis in cells that cannot convert L-kynurenine into quinolinic acid.

3-Hydroxyanthranilic Acid↗
PubMed1993

Kynurenine pathway enzymes in brain: responses to ischemic brain injury versus systemic immune activation.

Accumulation of L-kynurenine and quinolinic acid (QUIN) in the brain occurs after either ischemic brain injury or after systemic administration of pokeweed mitogen. Although conversion of L-[13C6]tryptophan to [13C6]-QUIN has not been demonstrated in brain either from normal gerbils or from gerbils given pokeweed mitogen, direct conversion in brain tissue does occur 4 days after transient cerebral ischemia. Increased activities of enzymes distal to indoleamine-2,3-dioxygenase may determine whether L-kynurenine is converted to QUIN. One day after 10 min of cerebral ischemia, the activities of kynureninase and 3-hydroxy-3,4-dioxygenase were increased in the hippocampus, but local QUIN levels and the activities of the indoleamine-2,3-dioxygenase and kynurenine-3-hydroxylase were unchanged. By days 2 and 4 after ischemia, however, the activities of all these enzymes in the hippocampus as well as QUIN levels were significantly increased. Kynurenine aminotransferase activity in the hippocampus was unchanged on days 1 and 2 after ischemia but was decreased on day 4, at a time when local kynurenic acid levels were unchanged. A putative precursor of QUIN, [13C6]anthranilic acid, was not converted to [13C6]QUIN in the hippocampus of either normal or 4-day post-ischemic gerbils. Gerbil macrophages stimulated by endotoxin in vitro converted L-[13C6]tryptophan to [13C6]QUIN. Kinetic analysis of kynurenine-3-hydroxylase activity in the cerebral cortex of postischemic gerbils showed that Vmax increased, without changes in Km. Systemic administration of pokeweed mitogen increased indoleamine-2,3-dioxygenase and kynureninase activities in the brain without significant changes in kynurenine-3-hydroxylase or 3-hydroxyanthranilate-3,4-dioxygenase activities. Increases in kynurenine-3-hydroxylase activity, in conjunction with induction of indoleamine-2,3-dioxygenase, kynureninase, and 3-hydroxyanthranilate-3,4-dioxygenase in macrophage infiltrates at the site of brain injury, may explain the ability of postischemic hippocampus to convert L-[13C6]tryptophan to [13C6]QUIN.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1993

Sleep-related injuries in the U.S. Army, 1984-1991.

U.S. Army Safety Center files for the years 1984-1991 were searched for ground accidents involving sleeping soldiers. There were 68 incidents which could be so categorized, 53 of which resulted in injuries and 15 in fatalities. The average cost to the Army, adjusted to 1991 dollars, was $8,300 for each injury and $61,900 for each fatality. The injured required an average 24.6 days of lost duty time for recovery. The incidents most commonly occurred when soldiers slept near vehicles and less commonly when they slept in designated "safe" areas. With improved guidance and training, such accidents could be reduced.

Fatigue↗
PubMed1993

Helicopter rotor blade injury: a persistent safety hazard in the U.S. Army.

Rotor blade injuries are an inherent hazard of helicopter operations. To determine the recent incidence of rotor blade injuries in the U.S. Army, a review of accident records (1972-91) was conducted. Crash-related injuries were not included. During the study period, there were 24 blade strike injuries (12 involving the main rotor), 11 (46%) of which were fatal. Comparison with previous reports indicates a lower rotor blade injury rate in the last decade than in any previous period. The head was injured most frequently (65%), followed by the chest (17%) and abdomen (7%). Protective helmets helped to reduce injury in several instances. Flight crew comprised 49% of the victims, passengers 29%, ground crew 14%, and bystanders 8%. Helicopter crews must maintain situational awareness when around turning blades--professional training alone does not guarantee protection from rotor blade injury.

Accidents, Occupational↗
PubMed1992

Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease.

Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy.

Aged↗
PubMed1992

Effect of high terrestrial altitude and supplemental oxygen on human performance and mood.

Sustained exposure to high terrestrial altitudes is associated with cognitive decrement, mood changes, and acute mountain sickness (AMS). Such impairment in aviators could be a safety hazard. Thirteen male soldiers, ages 19-24, ascended in 10 min from sea level to 4,300 m (simulated), and remained there 2.5 d. Four times per day, subjects completed a test battery consisting of nine cognitive tests, a mood scale, and an AMS questionnaire. During one test session per day, subjects breathed 35% oxygen instead of ambient air. Analysis revealed transient deficits on altitude day 1 for three cognitive tasks. Most tasks displayed a persistent training effect. Sick subjects' moods were more negative and their performance improvement less. On altitude day 1, oxygen administration improved performance on two cognitive tests and one mood subscale. Following rapid ascent to 4,300 m, performance is most affected during the first 8 h. Individuals affected by AMS tend to improve more slowly in performance and have more negative moods than those who feel well.

Adult↗
PubMed1991

Should helicopter frequent flyers wear head protection? A study of helmet effectiveness.

Flight helmets have been recommended as aircrew head protection since 1908, yet debate continues regarding their effectiveness. Estimates of helmet use in civilian helicopter aeromedical programs range from 6.5% to 13%. The effectiveness of the Army's SPH-4 flight helmet in reducing severe head injuries sustained during helicopter accidents was evaluated using the accident data base at the US Army Safety Center, Fort Rucker, Alabama. Analysis was restricted to severe (Class A) accidents that were at least partially survivable, using US Army Safety Center criteria. Occupants not wearing a protective helmet were significantly more likely to sustain severe and fatal head injuries than were occupants wearing the SPH-4 (RR = 3.8 and 6.3, respectively; P less than .01). Unhelmeted noncockpit occupants were at higher risk of head injuries (RR = 5.3 and 7.5; P less than .01). All personnel regularly participating in helicopter flight, civilian or military, should be equipped with protective headgear.

Accidents, Aviation↗
PubMed1987

Simulator sickness: a problem for Army aviation.

"Simulator Sickness" describes a symptom complex frequently reported by pilots during or after flight simulator training. There were 112 helicopter pilots at a U.S. Army AH-1 Cobra Flight Weapons Simulator (FWS) who completed a symptom-oriented subjective questionnaire. Of these, 40% reported symptoms of dysequilibrium; pilots developing simulator sickness had significantly more total and AH-1 flight time. Adaptation to the syndrome occurred with increasing FWS experience. The history and aeromedical significance of simulator sickness are briefly reviewed, and a case report presented. A mandatory grounding policy in use locally is described. Potential treatment strategies are briefly discussed.

Adult↗
PubMed1986

The prevalence and correlates of echocardiographic left ventricular hypertrophy among employed patients with uncomplicated hypertension.

To determine the prevalence and correlates of echocardiographic left ventricular hypertrophy among subjects in a general population, we studied 621 employed subjects. Patients with uncomplicated essential hypertension in a worksite-based treatment program included 145 with borderline hypertension and 316 with sustained hypertension by World Health Organization criteria. Normotensive subjects were randomly selected from members of the same unions. M-mode echocardiographic left ventricular dimensions were used to calculate left ventricular mass and other indexes of left ventricular anatomy. The specificity of 13 echocardiographic criteria of left ventricular hypertrophy was determined in normotensive individuals, and the prevalence of left ventricular hypertrophy by each criterion was assessed in patients with borderline or sustained essential hypertension. The results suggest that the most suitable reference standard for detection of left ventricular hypertrophy in a heterogeneous urban population utilizes sex-specific cutoff values for left ventricular mass index of 110 g/m2 or greater for women and 134 g/m2 or greater for men. With 97% specificity, the prevalence of left ventricular hypertrophy by these criteria is approximately 12% among patients with borderline hypertension and 20% among patients with relatively mild, uncomplicated sustained essential hypertension. Wall thickness measurements performed slightly less well. At similar levels of blood pressure, black patients were more likely than white patients to exhibit concentric left ventricular hypertrophy, especially among borderline hypertensive patients. Left ventricular hypertrophy occurred in patients with sustained hypertension who also exhibited increased cardiac output, strongly associated with low plasma renin activity.

Adult↗