Indigofera spicata (creeping indigo) poisoning of three ponies.

Three ponies continuously grazed a pasture containing an estimated 24% Indigofera spicata (wet weight basis) for 4-6 weeks in April and May 2004. They developed ataxia, paresis, depression, muscle fasciculations, dysphagia, ptyalism and halitosis. Two also developed corneal opacity. One pony recovered with supportive treatment, but the other two were euthanased and necropsied. Neuropathology was not present in either case, but both livers had periacinar and periportal lymphocytic infiltrations and hydropic degeneration of mid-zonal hepatocytes, with mild to moderate periacinar necrosis also evident in one. The I. spicata contained 2.66 mg 3-nitropropionic acid (3-NPA)/g dry matter and 1.5 mg indospicine/g dry matter. Indospicine, but not 3-NPA, was detected in serum from both of the euthanased ponies and indospicine was detected in heart, liver and muscle from the one pony in which this assay was performed. The clinical syndrome closely resembled 'Birdsville horse disease' caused by I. linnaei and was similar to that reported in horses poisoned by the closely related species I. hendecaphylla and to 3-NPA poisoning of other animals, including humans. 3-NPA is thought to cause this neurological syndrome. To our knowledge, this is the first authenticated report of I. spicata poisoning in grazing animals. We also report here the first published evidence that 3-NPA and indospicine exist in naturalised I. spicata in Australia and of the formation of indospicine residues in tissues of animals grazing paddocks infested with I. spicata.

Fatal cetacean morbillivirus infection in an Australian offshore bottlenose dolphin (Tursiops truncatus).

A juvenile offshore bottlenose dolphin (Tursiops truncatus) was found stranded with neurological signs and unable to swim or float unassisted. It subsequently died, succumbing to a combination of severe pneumonia and encephalitis. Morbillivirus serum neutralisation test serology was positive (titre 1:16) for cetacean morbillivirus and negative for both phocine distemper virus and canine distemper virus. There was concurrent thymic and lymph node lymphoid depletion and necrosis, together with intranuclear and intracytoplasmic acidophilic viral inclusion bodies and multinucleate syncytia within multiple organs. Paramyxovirus capsids were identified in lung sections via electron microscopy and morbillivirus antigen was demonstrated within sections of lung, thymus and brain by immunohistochemistry. Reverse transcription-polymerase chain reaction for morbillivirus nucleoprotein (N) and phosphoprotein (P) genes were positive and phylogenetic gene product sequence analysis revealed 98% and 94% sequence identity to dolphin morbillivirus, respectively. To the authors' knowledge, this is the first report of a cetacean mortality due to morbillivirus infection occurring in the southern hemisphere. Morbillivirus infection should be included in the differential diagnosis of stranded live or dead cetaceans in Australian waters, particularly if animals display neurological signs.

Myofibroblastic fibrosarcoma with multifocal osseous metaplasia at the site of equine influenza vaccination.

We describe a fibrosarcoma in a 12-year-old Quarterhorse x Arabian gelding as a sequela to equine influenza vaccination. Shortly after the second vaccination, swelling at the site was noticed by the owner and it continued to increase in size over the following 6 months. Biopsy of the mass indicated a fibrosarcoma had developed at the vaccination site. It was approximately 20 cm in diameter and elevated well above the level of the skin. There was no clinical evidence of metastases to the lungs or local lymph nodes. Surgical resection of the mass was performed and the wound healed by first and second intention. Histopathological examination and immunohistochemical staining confirmed a myofibroblastic fibrosarcoma with multifocal osseous metaplasia. To the authors' knowledge, this is the first equine case of a vaccine-associated fibrosarcoma.

Antihypertensive therapy in critical occupations: studies with an angiotensin II antagonist.

OBJECTIVE: This study was performed to establish whether an angiotensin II antagonist modulates daytime sleepiness or performance. METHODS: The central effects of losartan (50 and 100 mg), as well as amlodipine (5 and 10 mg) and promethazine (10 mg), were studied in six healthy volunteers (aged between 20 and 27 (mean 24) yr). Digit symbol substitution, tracking, vigilance, immediate and short-term memory recall, complex reaction time, together with objective (daytime sleep latencies) and subjective measures of sleepiness, were measured 1.0 h before and 0.5, 2.0, 3.5, 5.0, 6.5, and 8.0 h after ingestion. The study was placebo-controlled and double-blind with a six-way crossover design. RESULTS: No changes in performance or in measurements related to sleepiness were observed with losartan (50 and 100 mg). Amlodipine (10 mg) impaired immediate memory and increased subjective sleepiness at 8.0 h (p < 0.05). Promethazine (10 mg) impaired vigilance and immediate memory recall and increased reaction time (basic and complex) from 2.0 to 6.5 h after ingestion, impaired tracking from 3.5 to 6.5 h and increased subjective sleepiness from 2.0 to 8.0 h (p < 0.05). CONCLUSION: The study suggests that an angiotensin II antagonist could prove useful for the treatment of hypertension in aircrew.

Hypnotic activity of melatonin.

OBJECTIVE: To establish the effect of melatonin upon nocturnal and evening sleep. METHODS: Experiment I: The effect of melatonin (0.1, 0.5, 1.0, 5.0, and 10 mg), ingested at 23:30, was studied on nocturnal sleep (23:30-07:30) and core body temperature in 8 healthy volunteers. Performance was measured 8.5 h post-ingestion. On completion of the experiment dim light melatonin onsets (DLMO) were determined. Experiment II: The effect of melatonin (0.5, 1.0, 5.0, and 10 mg), ingested at 18:00, was studied on evening sleep (18:00-24:00) and core body temperature in 6 healthy volunteers. Performance was measured 6.5 h post-ingestion. Each experiment was placebo-controlled and double-blind with a cross-over design with temazepam (20 mg) as an active control. RESULTS: Experiment I: Melatonin (5 mg) reduced the duration of stage 3 in the first 100 min of sleep. Melatonin (0.1 mg) reduced body temperature 6.5 to 7 h post-ingestion. Temazepam increased stage 2, reduced wakefulness and stage 1, and increased the latency to REM sleep. Temazepam reduced body temperature 4.5 to 6.5 h post-ingestion. There were no changes in performance compared with placebo. DLMO occurred between 20:40 and 23:15. Experiment II: Melatonin (all doses) increased total sleep time (TST), sleep efficiency index (SEI) and stage 2, and reduced wakefulness. Temazepam increased TST, SEI, stage 2 and slow-wave sleep, and reduced wakefulness. There were no changes in body temperature or performance compared with placebo. CONCLUSION: Melatonin given at 23:30 has no significant clinical effect on nocturnal sleep in healthy individuals. Hypnotic activity of melatonin when given in the early evening (presumably in the absence of endogenous melatonin) is similar to 20 mg temazepam.

Antihistamines and aircrew: usefulness of fexofenadine.

INTRODUCTION: The aim of this study was to establish whether fexofenadine hydrochloride, an antihistamine, modulates daytime sleepiness or performance. METHODS: The effects of fexofenadine (120, 180, and 240 mg) on digit symbol substitution, tracking, and vigilance tasks, and on objective (multiple sleep latency test) and subjective sleepiness, were studied in six healthy volunteers (two males, four females, aged 20-34 [mean 26.5] yr) from 1 h pre-ingestion to 8 h post-ingestion. The study was placebo-controlled and double-blind with a six-way cross-over design. The centrally acting antihistamine, promethazine (10 mg), was used as an active control to confirm the sensitivity of the experimental procedures. RESULTS: There were no changes in performance or sleepiness with any dose of fexofenadine at any time, compared with placebo. Promethazine, compared with both placebo and fexofenadine, impaired performance on the digit symbol substitution task (2.5 h post-ingestion), vigilance task (2.5-5h post-ingestion) and tracking task (2.5-3.5 h post-ingestion), increased objective sleepiness (1.5-2.5 h post-ingestion) and subjective sleepiness (1.5-8h post-ingestion). CONCLUSION: Consideration may be given to the clinical use of currently licensed doses of fexofenadine (120-180 mg) by individuals involved in skilled activity. Fexofenadine may be potentially useful for aircrew.

Making the health care delivery system accountable.

Accountability has become the fact of life for the health care provider and the delivery system. Until recently, accountability has been viewed primarily through the judicial process as issues of fraud and liability, or by managed care entities through evaluation of the financial bottom line. It is this second consideration and its ramifications that will be explored in this article. Appropriate measurement tools are needed to evaluate services, delivery, performance, customer satisfaction, and outcomes assessment. Measurement tools will be considered in light of the industry's unique considerations and realities. All participants, including insurers, employers, management, and health care providers and recipients, bear responsibilities which necessitate assessment and analysis. However, until the basic question, "Who is the customer?" is resolved, accountability issues remain complex and obscured. Accountability costs and impacts must be evaluated over time. They go way beyond bottom line cost containment and reduction. Accountability will be accomplished when the health care industry implements quality and measurement concepts that yield the highest levels of validity and appropriateness for health care delivery.

Complex effects of melatonin on human circadian rhythms in constant dim light.

In humans, the pineal hormone melatonin can phase shift a number of circadian rhythms (e.g., "fatigue", endogenous melatonin, core body temperature) together with the timing of prolactin secretion. It is uncertain, however, whether melatonin can fully entrain all human circadian rhythms. In this study, the authors investigated the effects of daily melatonin administration on sighted individuals kept in continuous very dim light. A total of 10 normal, healthy males were maintained in two separate groups in partial temporal isolation under constant dim light (< 8 lux) with attenuated sound and ambient temperature variations but with knowledge of clock time for two periods of 30 days. In these circumstances, the majority of individuals free run with a mean period of 24.3 h. In a double-blind, randomized crossover design, subjects received 5 mg melatonin at 20:00 h on Days 1 to 15 (Melatonin 1st) followed by placebo on Days 16 to 30 (Placebo 2nd) or vice versa (Placebo 1st, Melatonin 2nd) during Leg 1 with treatment reversed in Leg 2. The variables measured were melatonin (as 6-sulphatoxymelatonin), rectal temperature, activity, and sleep (actigraphy and logs). In the experiment, 9 of the 10 subjects free ran with Placebo 1st, whereas Melatonin 1st stabilized the sleep-wake cycle to 24 h in 8 of 10 individuals. In addition, 2 individuals showed irregular sleep with this treatment. In some subjects, there was a shortening of the period of the temperature rhythm without synchronization. Melatonin 2nd induced phase advances (5 of 9 subjects), phase delays (2 of 9 subjects), and stabilization (2 of 9 subjects) of the sleep-wake cycle with subsequent synchronization to 24 h in the majority of individuals (7 of 9). Temperature continued to free run in 4 subjects. Maximum phase advances in core temperature were seen when the first melatonin treatment was given approximately 2 h after the temperature acrophase. These results indicate that melatonin was able to phase shift sleep and core temperature but was unable to synchronize core temperature consistently. In the majority of subjects, the sleep-wake cycle could be synchronized.

Promoting sleep in shiftworkers and intercontinental travelers.

A number of techniques and treatments can be used to alleviate the sleep disturbance associated with both shiftwork and transmeridian travel. Optimization of the sleeping environment and avoidance of substances such as caffeine and alcohol before sleep are the best initial approach. Timing sleep to coincide with some of the normal sleep period where possible will improve sleep quality in shiftworkers. Similarly, following transmeridian flight, restricting sleep to the nocturnal period in the new time zone will assist adaptation. Hypnotic drugs may be of benefit to alleviate sleep disturbance experienced by shiftworkers or transmeridian travelers. Selection of the most appropriate medication must take into account required duration of action and possible residual effects of the drug on alertness. Hypnotics may be useful, particularly in middle-aged individuals who already have disturbed sleep, on those occasions when poor sleep is anticipated, for example following an eastward flight or after the initial change to night duty. Over-the-counter preparations should be avoided whenever possible unless it is known that they are not associated with residual sequelae.

Human circadian rhythms in constant dim light (8 lux) with knowledge of clock time.

The light/dark (L/D) cycle is a major synchronizer of human circadian rhythms. In the absence of a strong L/D cycle, synchrony with 24 hours can nevertheless be maintained in a socially structured environment, as shown in Polar regions (Broadway et al. 1987) and by some blind subjects (Czeisler et al. 1995a). The relative contribution of other time cues to entrainment in dim light has not been fully explored. The present study investigated the behaviour of melatonin (assessed as 6-sulphatoxymelatonin); rectal temperature; activity and sleep (actigraphy and logs) in constant dim light (L/ L) with access to a digital clock. 6 normal healthy males were maintained as a group in partial temporal isolation with attenuated sound and ambient temperature for 21 days. All 6 subjects showed free-running periodicity for 6-sulphatoxymelatonin and 5/6 subjects for temperature, activity and sleep offset. The average period (tau) was 24.26 +/- 0.049, substantially shorter than in previous experiments with a self selected L/D cycle but similar to a recent study conducted in very dim light. One subject maintained a rigid sleep/wake cycle throughout whilst his 6-sulphatoxymelatonin rhythm free-ran. Total sleep time, from actigraph data, did not change but sleep efficiency decreased during the experiment. The subjects did not show group synchronization. These results confirm previous data indicating the importance of the L/D cycle in human entrainment and underline the lesser role of social cues and knowledge of clock time. This particular approach will permit the administration of timed medication to sighted humans under free-running conditions.

Psychophysiological correlates of dynamic imagery.

Brain Electrical Activity Maps were recorded from 20 subjects whilst performing: (a) the Vandenberg & Kuse Mental Rotation Test (MRT) and: (b) the Isaac, Marks & Russell Vividness of Movement Imagery Questionnaire (VMIQ), and under control conditions. Subjects were classified as good or poor imagers, first on the basis of their VMIQ scores, and secondly on their MRT scores. Alpha, beta 1 and beta 2 at different cortical regions were compared between groups and between task performance and control conditions. During MRT significant reductions in alpha amplitude were found over both right and left parietal areas and over the left frontal region. In beta 1 non-significant trends in the same direction were observed in the same regions found to be significant in alpha. Non-significant trends in beta 2 were observed over the right parietal and frontal regions. No differences in amplitude at any frequency band were found between good and poor VMIQ scorers but subjects with high MRT scores showed greater alpha amplitude at many sites in the parietal, parieto-occipital and frontal areas than subjects with low MRT scores. During VMIQ testing the VMIQ high imagers showed a non-significant trend towards higher alpha amplitude at frontal regions and some scattered parietal and occipital sites and significantly higher levels of beta 2 in the left frontal region. However, no differences were found between imagery and control conditions. The results confirm the involvement of motor as well as spatial processes in dynamic imagery.

Influence of polar route schedules on the duty and rest patterns of aircrew.

The duty and rest periods of aircrew operating the polar route from London via Anchorage were recorded during five schedules which involved 1-, 2- or 3-day sojourns in Japan. Sleep throughout each schedule was fragmented, with naps before duty and short sleeps after arrival at a new location. Sleep disturbance rather than cumulative sleep loss appeared to be the overriding problem, and the shorter schedules had the most marked disturbances in sleep during the trip and during the immediate recovery period. Electroencephalographic studies are necessary to confirm these observations, and information on circadian rhythmicity is needed to define the circumstances which lead to persistence of sleep disturbance on return to Europe.

Sleep of Andean high altitude natives.

The structure of sleep in lowland visitors to altitudes greater than 4000 m is grossly disturbed. There are no data on sleep in long-term residents of high altitudes. This paper describes an electroencephalographic study of sleep in high altitude dwellers who were born in and are permanent residents of Cerro de Pasco in the Peruvian Andes, situated at 4330 m. Eight healthy male volunteers aged between 18 and 69 years were studied. Sleep was measured on three consecutive nights for each subject. Electroencephalographs, submental electromyographs and electro-oculograms were recorded. Only data from the third night were used in the analysis. The sleep patterns of these subjects resembled the normal sleep patterns described by others in lowlanders at sea level. There were significant amounts of slow wave sleep in the younger subjects and rapid eye movement sleep seemed unimpaired.

Circadian rhythmicity and sleep of aircrew during polar schedules.

Sleep and circadian rhythms of aircrew were studied during a 7-d polar schedule operated between London and Tokyo. Sleep, rectal temperature, and subjective alertness were recorded for 2 d before departure during the schedule, and for 10 d after the return. Changes in sleep during the early part of the trip were due to sleep loss on the outward journey, but later these changes were related to the displacement of the circadian rhythm. The acrophases of the circadian rhythms of temperature were delayed by the outward journey, and amplitudes were reduced throughout the trip. During the return, aircrew reported high levels of tiredness which persisted until the second recovery night. Though the amounts of sleep obtained during the schedule were satisfactory for the aircrew as a group, some crewmembers experienced difficulties. Realignment of circadian rhythms was attained by an advance of the circadian phase in eight aircrew and by a delay in three, and resynchronization was achieved in all cases within 6 d.

Performance and quality of sleep wearing NBC protective clothing.

Two separate studies were carried out to investigate the effect of wearing nuclear-biological-chemical aircrew equipment assembly (NBC AEA) protective clothing on performance and on overnight sleep. Performance at a series of tasks was measured, in six male subjects, during the day (0800-2000 hours) and at night (2000-0800 hours). Wearing the NBC assembly did not lead to significant decrements in performance compared with the normal aircrew equipment assembly (AEA). The sleep of six male volunteers was recorded electroencephalographically on two consecutive nights when NBC protective clothing was worn. Sleep was both shortened and disturbed, compared with overnight control sleep. There were some improvements on the second night, suggesting that individuals may adapt to wearing the NBC assembly.

Combined optical second harmonic generation/quartz crystal microbalance study of underpotential deposition processes: copper electrodeposition on polycrystalline gold.

Optical second harmonic generation and quartz crystal microbalance techniques are used as in situ probes of copper underpotential deposition on polycrystalline gold surfaces in sulfuric acid electrolyte. The second harmonic signal from a polished bulk gold substrate is observed to decrease by >60% as a result of copper underpotential deposition on gold. Also, the mass of an underpotentially deposited copper adlayer is monitored in situ by an oscillating quartz crystal microbalance, yielding an estimated coverage of ~8.0 x 10(-10) mol cm(-2) and an electrosorption valency of 1.5 for a copper adlayer on the surface of vapor-deposited polycrystalline gold.

The influence of a 1 h nap on performance overnight.

The effect on performance overnight of a 1 h nap taken at 0200 h was studied in six young female subjects. The subjects completed three schedules, including one with a nap and two without a nap, during which either a placebo or 300 mg caffeine was ingested at 2315 h. Performance was measured from 1700 h in the evening until 1030 h the next morning. Caffeine improved performance overnight on almost all tasks compared with placebo. The nap had some limited beneficial effect compared with placebo, but most tasks remained impaired.