bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional magnetic resonance imaging neuroactivation studies in normal subjects and subjects with the narcoleptic syndrome. Actions of modafinil
Authors: Ellis C.M. , Monk C. , Simmons A. , Lemmens G. , Williams S.C.R. , Brammer M. , Bullmore E. , Parkes J.D. 
Published: March 2003

SummaryFunctional magnetic resonance imaging (fMRI) can be used to detect regional brain responses to changes in sensory stimuli. We have used fMRI to determine the amount of visual and auditory cortical activation in 12 normal subjects and 12 subjects with the narcoleptic syndrome, using a multiplexed visual and auditory stimulation paradigm. In both normal and narcoleptic subjects, mean cortical activation levels during the presentation of periodic visual and auditory stimulation showed no appreciable differences with either age or sex. Normal subjects showed higher levels of visual activation at 10:00 hours than 15:00 hours, with a reverse pattern in narcoleptic subjects (P=0.007). The group differences in spatial extent of cortical activation between control and narcoleptic subjects were small and statistically insignificant. The alerting action, and imaging response, to a single oral dose of the sleep‐preventing drug modafinil 400 mg were then determined and compared with placebo in both the 12 normal (8 given modafinil, 4 placebo) and 12 narcoleptic subjects (8 modafinil, 4 placebo). Modafinil caused an increase in self‐reported levels of alertness in 7 of 8 narcoleptic subjects, but there was no significant difference between mean pretreatment and post‐treatment activation levels as determined by fMRI for either normal or narcoleptic syndrome subjects given modafinil. However, in the modafinil‐treated group of 8 normal and 8 narcoleptic subjects, there was a clock time independent correlation between the initial level of activation as determined by the pretreatment scan and the post‐treatment change in activation (visual, P=0.002; and auditory, P=0.001). No correlation was observed in placebo‐treated subjects (P=0.99 and 0.77, respectively).Although limited by the small number of subjects, and the lack of an objective measure of alertness, the findings of this study suggest that low cortical activation levels in both normal and narcoleptic subjects are increased following the administration of modafinil. Functional magnetic resonance imaging may be a valuable addition to established studies of attention.
Atrial natriuretic peptide levels and pulmonary artery pressure awake, at exercise and asleep in obstructive sleep apnoea syndrome
Authors: Schäfer Harald , Ehlenz Klaus , Ewig Santiago , Hasper Ekkhard , Koehler Ulrich , Latzelsberger Jan , Tasci Selcuk , Lüderitz Berndt 
Published: March 2003

SummaryElevated nocturnal plasma atrial natriuretic peptide (ANP) levels were found in patients with obstructive sleep apnoea (OSA). The purpose of our study was to examine the secretion of ANP during the night and to measure changes in oxygen saturation, pulmonary artery pressure and intrathoracic pressure swings in patients with OSA. Moreover, we analysed the secretion of ANP and the pulmonary artery pressure in different behavioural states, e.g. awake, at exercise and asleep. Consecutive apnoeas in non‐rapid eye movement (NREM) sleep at the beginning, middle and end of the sleep study were analysed in six patients with obstructive sleep apnoea. In addition, we measured the plasma levels of ANP. The apnoea duration was significantly longer (P< 0.05) at the middle of the sleep study than at the beginning or end. Correspondingly, the end‐apnoeic oxygen saturation and end‐apnoeic oesophageal pressure were both significantly lower (P< 0.05) in the middle of the sleep study than at the beginning or end. No significant differences were found in the end‐apnoeic systolic transmural pulmonary artery pressure (PPA™) and the levels of ANP. Evaluation of the ANP levels during different behavioural states revealed that the asleep levels were slightly, but not significantly, higher than the awake levels (0.235±0.088 vs. 0.207±0.057 nmol/L). However, the highest levels were found during exercise (0.334±0.170 nmol/L) with a significant difference compared with the awake and asleep levels. These data suggest that volume effects may be a potent factor in liberating ANP during exercise, but the role of OSA in ANP secretion when asleep is questionable.
Comparison between subjective and actigraphic measurement of sleep and sleep rhythms
Authors: Lockley Steven W. , Skene Debra J. , Arendt Josephine 
Published: March 2003

SummarySleep is often assessed in circadian rhythm studies and long‐term monitoring is required to detect any changes in sleep over time. The present study aims to investigate the ability of the two most commonly employed methods, actigraphy and sleep logs, to identify circadian sleep/wake disorders and measure changes in sleep patterns over time. In addition, the study assesses whether sleep measured by both methods shows the same relationship with an established circadian phase marker, urinary 6‐sulphatoxymelatonin. A total of 49 registered blind subjects with different types of circadian rhythms were studied daily for at least four weeks. Grouped analysis of all study days for all subjects was performed for all sleep parameters (1062–1150 days data per sleep parameter). Good correlations were observed when comparing the measurement of sleep timing and duration (sleep onset, sleep offset, night sleep duration, day‐time nap duration). However, the methods were poorly correlated in their assessment of transitions between sleep and wake states (sleep latency, number and duration of night awakenings, number of day‐time naps). There were also large and inconsistent differences in the measurement of the absolute sleep parameters. Overall, actigraphs recorded a shorter sleep latency, advanced onset time, increased number and duration of night awakenings, delayed offset, increased night sleep duration and increased number and duration of naps compared with the subjective sleep logs. Despite this, there was good agreement between the methods for measuring changes in sleep patterns over time. In particular, the methods agreed when assessing changes in sleep in relation to a circadian phase marker (the 6‐sulphatoxymelatonin (aMT6s) rhythm) in both entrained (n= 30) and free‐running (n= 4) subjects.
Level of arousal and the ability to maintain wakefulness
Authors: Bonnet Michael H. , Arand Donna L. 
Published: March 2003

SummaryThe ability to maintain wakefulness under baseline and sleep deprivation conditions was examined in a group of 14 normal young adults. Subjects participated in both standard and manipulation Maintenance of Wakefulness tests after being awake for 7, 19, and 31 h. In the manipulation Maintenance of Wakefulness tests, subjects performed varying degrees of physical activity at the onset of stage 1 to allow them to preserve wakefulness. As expected, ability to maintain wakefulness declined as time awake increased. With amount of time awake held constant, wakefulness was enhanced most after standing and doing knee bends, less after standing, less after sitting up, and least after subjects were spoken to. The improvement in alertness after doing knee bends as compared to being spoken to was of the same relative magnitude as the decrease in alertness after one night of total sleep deprivation. As expected, heart rate also increased consistently as activity increased. Each subject had a negative correlation between their EEG sleep latencies and their minimum r‐r interval during the manipulation, i.e. the higher the heart rate, the longer the latency. These data were interpreted as a demonstration of the impact of discrete phasic arousal on the ability to maintain wakefulness.
Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the Epworth sleepiness scale: Failure of the MSLT as a gold standard
Authors: Johns Murray W. 
Published: March 2003

SUMMARYExcessive daytime sleepiness (EDS) is an important symptom that needs to be quantified, but there is confusion over the best way to do this. Three of the most commonly used tests: the multiple sleep latency test (MSLT), the maintenance of wakefulness test (MWT) and the Epworth sleepiness scale (ESS) give results that are significantly correlated in a statistical sense, but are not closely related. The purpose of this investigation was to help clarify this problem. Previously published data from several investigations were used to calculate the reference range of normal values for each test, defined by the mean±2 SD or by the 2.5 and 97.5 percentiles. The ‘rule of thumb’ that many people rely on to interpret MSLT results is shown here to be misleading. Previously published results from each test were also available for narcoleptic patients who were drug‐free at the time and who by definition had EDS. This enabled the sensitivity and specificity of the three tests to be compared for the first time, in their ability to distinguish the EDS of narcolepsy from the daytime sleepiness of normal subjects. The receiver operator characteristic curves clearly showed that the ESS is the most discriminating test, the MWT is next best and the MSLT the least discriminating test of daytime sleepiness. The MSLT can no longer be considered the gold standard for such tests.
Correlates of nap taking in mothers of young infants
Authors: Cottrell Lesley , Karraker Katherine Hildebrandt 
Published: March 2003

SummaryMany researchers and clinicians have promoted nap taking to combat the deleterious effects of disrupted sleep. Unfortunately, only a small portion of sleep‐deprived individuals take naps. The goal of the present study was to identify cognitive and opportunity factors related to nap taking of mothers of young infants. Fifty‐one mothers of young infants completed measures that recorded various characteristics of their nighttime sleep patterns, their perceptions of their sleep, and factors influencing their opportunities to take naps. Results revealed that mothers' perceptions of sleep disturbance and opportunity factors were more predictive of napping than total nighttime sleep or actual time spent caring for the infant during the night.
The 3111 Clock gene polymorphism is not associated with sleep and circadian rhythmicity in phenotypically characterized human subjects
Authors: Robilliard Donna L. , Archer Simon N. , Arendt Josephine , Lockley Steven W. , Hack Lisa M. , English Judie , Leger Damien , Smits Marcel G. , Williams Adrian , Skene Debra J. , Von Schantz Malcolm 
Published: March 2003

SUMMARYMutations in clock genes are associated with abnormal circadian parameters, including sleep. An association has been reported previously between a polymorphism (3111C), situated in the 3′‐untranslated region (3′‐UTR) of the circadian gene Clock and evening preference. In the present study, this polymorphism was assessed in: (1) 105 control subjects with defined diurnal preference, (2) 26 blind subjects with free‐running circadian rhythms and characterized with regard to circadian period (τ) and (3) 16 delayed sleep phase syndrome patients. The control group was chosen from a larger population (n = 484) by Horne‐Östberg questionnaire analysis, from which three subgroups were selected (evening, intermediate and morning preference). Data from sleep diaries completed by 90% of these subjects showed a strong correlation between preferred and estimated timings of sleep and wake. The mean timings of activities for the evening group were at least 2 h later than the morning group. Genetic analysis showed that, in contrast with the previously published finding, there was no association between 3111C and eveningness. Neither was there an association between 3111C and τ, nor a significant difference in 3111C frequency between the normal and delayed sleep phase syndrome groups. To assess the effect of this polymorphism on messenger RNA (mRNA) translatability, luciferase reporter gene constructs containing the two Clock polymorphic variants in their 3′‐UTR were transfected into COS‐1 cells and luciferase activity measured. No significant difference was observed between the two variants. These results do not support Clock 3111C as a marker for diurnal preference, τ, or delayed sleep phase syndrome in humans.
Pharmacokinetics and pharmacodynamics of tilmicosin in sheep and cattle
Authors: Modric  , Webb  , Derendorf  
Published: March 2003

Tilmicosin is a long‐acting macrolide antibiotic currently approved for treatment of bovine respiratory disease in the USA. Serum pharmacokinetics of tilmicosin were compared between cattle (major species) and sheep (minor species) after subcutaneous injection in order to evaluate a new potential application of the drug in currently nonapproved species. There were no significant differences in the elimination rates, maximum serum concentrations, half‐lives (t1/2), areas under the curve (AUC), areas under the first‐moment curve (AUMC), and mean residence times. Volume of distribution (Vdarea) and clearance (Cl), when normalized by body weight, were also similar. The only significantly different parameter was time at which maximum drug concentration was reached (tmax), with sheep having the tmax of 3.9 h, compared to 0.5 h in cattle. Although macrolides are considered to be one of the safest anti‐infective drugs, adverse cardiovascular effects of several macrolides have been reported. The cardiopulmonary effects of tilmicosin were monitored in healthy adult sheep after receiving a single subcutaneous (s.c.) injection of tilmicosin at the dose of 10 mg/kg, and no significant changes were found. The study indicates that tilmicosin can be used safely and effectively in sheep at the given dose, with no adverse cardiopulmonary effects.
The evaluation of the role of CCK in the opioid modulation of the motility of the gastrointestinal tract in sheep
Authors: Kania  , Brikas  , BuÉno  , Fioramonti  , Zaremba‐Rutkowska  
Published: March 2003

The participation of central cholecystokinin‐8 (CCK‐8) receptors in the modulatory effect of D‐Ala2, N‐Me‐Phe4, Gly5‐ol enkephalin (DAGO), a selective μ–opioid receptor agonist, on the spike burst activity of the gastrointestinal tract (rumen, reticulum, antrum, duodenum, colon and caecum) in sheep was investigated. DAGO was infused intracerebroventricularly (i.c.v.) at doses of 0.1–1 μg/kg body weight (BW). It was shown that DAGO significantly inhibited myoelectrical activity of the wall of the forestomachs, abomasum and colon but stimulated this activity in the duodenum (rate of myoelectrical migrant complex‐MMC). The effects of DAGO were prevented by CCK‐8 antagonists (L‐364.718 and L‐365.260) previously infused at doses of 5–20 μg/kg BW. The results of this present study indicate that central receptors of CCK‐8 participated in the modulatory action of an opioid on myoelectrical activity of the gastrointestinal tract in sheep. Furthermore, this result suggests that CCK‐8 is released in response to μ‐receptor stimulation, because CCK‐8 antagonists (L 364.718 and L 365.260) prevented the modulatory action of DAGO on the gastrointestinal motility in sheep.
Plasma angiotensin converting enzyme activity and pharmacokinetics of benazepril and benazeprilat in cats after single and repeated oral administration of benazepril.HCl
Authors: King  , Humbert‐Droz  , Maurer  
Published: March 2003

The plasma pharmacokinetics of benazepril and its active metabolite, benazeprilat, were determined in cats after oral administration of benazepril.HCl at dosages of 0.25, 0.5 and 1.0 mg/kg as a single dose (n = 5 per group) and after once daily application for 8 days (n = 6 per group). Pharmacodynamics were assessed by measurement of plasma angiotensin converting enzyme (ACE) activity.After single administration of benazepril.HCl, maximum benazepril concentrations were recorded at the first sample (2 h) and declined relatively rapidly with an elimination half life (t½) of 1.4 h. Highest benazeprilat concentrations were recorded at the first sample (2 h) in most cats and declined biphasically with half lives of each phase of 2.4 and 27.7 h. With repeated administration, plasma benazeprilat concentrations accumulated slightly with accumulation ratios (R) of 1.46, 1.36 and 1.24 for the 0.25, 0.5 and 1.0 mg/kg dosages of benazepril.HCl, respectively (median value of 1.36 for all dosages).All three dosages of benazepril.HCl caused marked inhibition of plasma ACE activity in all cats. The maximum effect (Emax, % inhibition of ACE as compared to baseline) was  98% after single and 100% with repeated administration. The duration of action of benazepril.HCl was long, with > 87% (single) and > 90% (repeat) inhibition of plasma ACE persisting 24 h after dosing.Benazepril.HCl was well tolerated in all animals. Dosages of 0.25–1.0 mg/kg benazepril.HCl once daily are recommended for clinical testing in cats.
The effect of raloxifene on coronary arteries in aged ovariectomized ewes
Authors: Gaynor J. S. , Monnet E. , Selzman C. , Parker D. , Kaufman L. , Bryant H. U. , Mallinckrodt C. , Wrigley R. , Whitehill T. , Turner A. S. 
Published: March 2003

Background – Ovariectomized sheep are a useful model of postmenopausal osteoporosis and other postmenopausal conditions. Estrogen may have a protective effect on the coronary arteries in postmenopausal women. The effects of raloxifene, a selective estrogen receptor modulator, on coronary arteries in aged ovariectomized ewes was investigated.Methods and Results – Forty eight aged ewes were randomly assigned to undergo sham surgery (Sham, n=7), ovariectomy (OVX, n=10), ovariectomy with estradiol supplementation (OVXE, n=8), ovariectomy with raloxifene supplementation, 0.02 mg/kg per day (RAL1, n=10), or ovariectomy with raloxifene supplementation, 0.10 mg/kg per day (RAL2, n=13). Contrast coronary angiography was performed 6 months after intervention. Diameters of the right main and left anterior descending coronary arteries in the RAL1, RAL2 and Sham groups were not different from each other, but were significantly greater than the OVX and OVXE groups. Intracoronary nitroglycerin did not affect the relationships of the diameters in any group. There were no differences in vascular remodeling between the groups.Conclusions – The results indicate that raloxifene in this sheep model allows greater dilation of coronary arteries than estrogen. Raloxifene may provide a significant protective functional effect on coronary arteries in postmenopausal heart disease.
Effects of anti‐arthritic drugs on proteoglycan synthesis by equine cartilage
Authors: Frean S. P. , Cambridge H. , Lees P. 
Published: March 2003

Effects of anti‐arthritic drugs on proteoglycan synthesis by equine cartilage.J. vet. Pharmacol. Therap.25,289–298.The concentration–effect relationships of phenylbutazone, indomethacin, betamethasone, pentosan polysulphate (PPS) and polysulphated glycosaminoglycan (PSGAG), on proteoglycan synthesis by equine cultured chondrocytes grown in monolayers, and articular cartilage explants were measured. The effect of PSGAG on interleukin‐1βinduced suppression of proteogycan synthesis was also investigated. Proteoglycan synthesis was measured by scintillation assay of radiolabelled sulphate (35SO4) incorporation. Polysulphated glycosaminoglycan and PPS stimulated proteoglycan synthesis in chondrocyte monolayers in a concentration‐related manner with maximal effects being achieved at a concentration of 10 μg/mL. Polysulphated glycosaminoglycan reversed the concentration‐related suppression of proteoglycan synthesis induced by interleukin‐1β. Neither PSGAG nor PPS exerted significant effects on radiolabel incorporation in cartilage explants. Betamethasone suppressed proteoglycan synthesis by both chondrocytes and explants at high concentrations (0.1–100 μg/mL), but the effect was not concentration‐related. At low concentrations (0.001–0.05 μg/mL) betamethasone neither increased nor decreased proteoglycan synthesis. Phenylbutazone and indomethacin increased radiolabel incorporation in chondrocyte cultures but not in cartilage explants at low (0.1, 1 and 10 μg/mL), but not at high (20 and 100 μg/mL) concentrations. These findings may be relevant to the clinical use of these drugs in the treatment of equine disease.
Pharmacokinetics of an ampicillin/sulbactam (2:1) combination in rabbits
Authors: Escudero E. , Vicente M. S. , Serrano J. M. , Cárceles C. M. 
Published: March 2003

. Pharmacokinetics of an ampicillin/sulbactam (2:1) combination in rabbits.J. vet. Pharmacol. Therap.25,259–264.The pharmacokinetics of a 2:1 ampicillin–sulbactam combination in six rabbits, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were investigated by using a high performance liquid chromatographic method for determining plasma concentrations. The plasma concentration–time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The disposition curves for both drugs were best described by an open two‐compartment model after intravenous administration and a one‐compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method for ampicillin and sulbactam were 0.62 ± 0.09 and 0.45 ± 0.05 L/kg, respectively, and the total body clearances were 0.65 ± 0.04 and 0.42 ± 0.05 L/kg h, respectively. The elimination half‐lives of ampicillin after intravenous and intramuscular administration were 0.64 ± 0.11 and 0.63 ± 0.16 h, respectively, whereas for sulbactam the half‐lives were 0.74 ± 0.12 and 0.77 ± 0.17 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (73.34 ± 10.08% for ampicillin and 83.20 ± 7.41% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.20 ± 0.09 and 0.34 ± 0.15 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.07 ± 3.64 mg/L of ampicillin and 8.42 ± 1.74 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after intramuscular administration in rabbits.
Baleen whales: conservation issues and the status of the most endangered populations
Authors: Clapham Phillip J. , Young Sharon B. , Brownell Robert L. 
Published: March 2003

AbstractMost species of baleen whales were subject to intensive overexploitation by commercial whaling in this and previous centuries, and many populations were reduced to small fractions of their original sizes. Here, we review the status of baleen whale stocks, with an emphasis on those that are known or thought to be critically endangered. Current data suggest that, of the various threats potentially affecting baleen whales, only entanglement in fishing gear and ship strikes may be significant at the population level, and then only in those populations which are already at critically low abundance. The impact of some problems (vessel harassment, and commercial or aboriginal whaling) is at present probably minor. For others (contaminants, habitat degradation, disease), existing data either indicate no immediate cause for concern, or are insufficient to permit an assessment. While the prospect for many baleen whales appears good, there are notable exceptions; populations that are of greatest concern are those suffering from low abundance and associated problems, including (in some cases) anthropogenic mortality. These include: all Northern Right Whales Eubalaena glacialis, Bowhead Whales Balaena mysticetus of the Okhotsk Sea and various eastern Arctic populations, western Gray Whales Eschrichtius robustus, and probably many Blue Whale Balaenoptera musculus populations. We review the status of these populations and, where known, the issues potentially affecting their recovery. Although Humpback Whales Megaptera novaeangliae and Southern Right Whales Eubalaena australis were also heavily exploited by whaling, existing data indicate strong recovery in most studied populations of these species.