bluuebunny/crossref_metadata_2025 huggingface dataset:
Comorbidity of internal derangement of the temporomandibular joint and silent dysfunction of the cervical spine
Authors: Stiesch‐Scholz M. , Fink M. , Tschernitschek H.
Published: March 2003

summary  The aim of this evaluation was to examine correlations between internal derangement of the temporomandibular joint (TMJ) and cervical spine disorder (CSD). A prospective controlled clinical study was carried out. Thirty patients with signs and symptoms of internal derangement but without any subjective neck problems and 30 age‐ and gender‐matched control subjects without signs and symptoms of internal derangement were examined. The investigation of the temporomandibular system was carried out using a ‘Craniomandibular Index’. Afterwards an examiner‐blinded manual medical investigation of the craniocervical system was performed. This included muscle palpation of the cervical spine and shoulder girdle as well as passive movement tests of the cervical spine, to detect restrictions in the range of movement as well as segmental intervertebral dysfunction. The internal derangement of the TMJ was significantly associated with ‘silent’ CSD (t‐test, P < 0ḃ05). Patients with raised muscle tenderness of the temporomandibular system exhibited significantly more often pain on pressure of the neck muscles than patients without muscle tenderness of the temporomandibular system (t‐test, P < 0ḃ05). As a result of the present study, for patients with internal derangement of the TMJ an additional examination of the craniocervical system should be recommended.
Exploring the emotional support needs and coping strategies of family carers
Authors: Chambers M. , Ryan A. A. , Connor S. L.
Published: March 2003

This paper explores the emotional support needs and coping strategies of family carers derived from two focus group interviews, each group comprising seven family carers. The interviews were carried out in Northern Ireland as part of phase one of the ACTION (Assisting Carers using Telematics Interventions to meet Older persons Needs) project. The purpose of the interviews was to investigate family carers' needs and experiences, but this paper focuses specifically on the emotional support needs and coping strategies identified by group members. The issues discussed included information and social support needs, the emotional impact of caring, and coping with and adaptation to the caring role. The findings reveal that for the majority of family carers their experience was one of constant searching for support and information. The anxiety and frustration associated with inconsistent and irregular support and lack of information was a major source of concern for the carers in the study. However, the carers employed a number of positive and negative coping strategies to deal with the stress associated with their caregiving role. The study concluded with the recommendation for nurses and other health care professionals to become more proactive in assessing and meeting carers' emotional support needs.
Safety and security policies on psychiatric acute admission wards: results from a London‐wide survey
Authors: Bowers L. , Crowhurst N. , Alexander J. , Callaghan P. , Eales S. , Guy S. , Mccann E. , Ryan C.
Published: March 2003

Very little research evidence is available regarding current safety and security procedures on acute psychiatric wards. This includes controversial areas such as the temporary removal of personal property, the searching of patients and visitors, the use of alarms and modern technology, and locking of entrances to regulate those entering and leaving. This is also despite widening dismay over increasing violence within a variety of hospital settings, the comparatively high risk of physical assault faced by mental health professionals and an abundance of literature and training in regards to violence management and prevention. To gain an understanding of current safety and security measures, a London‐wide survey of acute admission wards was undertaken revealing a wide variety of measures and policies in operation. Over 100 NHS and private wards were sent questionnaires; there was a response rate of 70%. Results show that a significant proportion of acute admission wards are now locked at all times and a small proportion of units have 24‐hour security/reception staff on‐site and a low level of modern technology usage such as CCTV and electronic access systems. There is wide variation in items banned, restrictions placed on inpatients, and the searching of patients and visitors. Two independently varying emphases of ward security policies were identifiable, the first aimed at preventing harm to patients using door security, banning of item and restrictions on inpatients. The other is aimed at reducing risks to staff via searching of patients, use of security guards and sophisticated alarm systems. There is some preliminary evidence that these security policies are differentially associated with levels of absconding and violent incidents. Further research to guide practice is urgently required.
Violence risk assessment: combining actuarial and clinical information to structure clinical judgements for the formulation and management of risk
Authors: DOYLE M. , DOLAN M.
Published: March 2003

Throughout history most societies have assumed a link between mental disorder and violence to others. In recent times there has been increasing concern in the United Kingdom over law and order, specifically the risk of violence, and these issues are now high on the political and mental health agenda. Nurses and staff working in National Health Service Mental Health Service Trusts are the groups most at risk of violence. Many clinical decisions are based on risk. Mental health nurses play a pivotal role in the assessment and management of risk and it is argued that they need to adopt a clear structured approach to violence risk assessment and management, which is evidence‐based. The advantages of clinical and actuarial approaches to risk assessment are briefly reviewed and a structured clinical judgement approach is proposed that combines these approaches. A method of linking the assessment process with the management plan via a risk formulation is discussed.
Voting as a means of social inclusion for people with a mental illness
Authors: NASH M.
Published: March 2003

People suffering from mental illness are often disenfranchized from many functions of society. Voting is one such area where disenfranchizement and exclusion are unnecessarily experienced. The emphasis on service provision as a means of achieving social inclusion for those with mental illness may relegate it to a principle of treatment compliance. Should measures of social function remain the main indicators of successful community care or should measures of social integration be identified, assessed and maintained? Mental health professionals should actively pursue users’ voting rights in light of the changing legal climate and the introduction of human rights legislation into United Kingdom law. With the potentially huge political capital in this area the author believes that the current debate regarding social inclusion cannot be adequately addressed unless this fundamental and democratic principle is included more extensively.
Too tired to care? The psychological effects of working with trauma
Authors: COLLINS S. , LONG A.
Published: March 2003

This quantitative and qualitative longitudinal study was designed to examine the effects on caregivers working therapeutically with seriously traumatized people. The participants were 13 healthcare workers seconded into a trauma and recovery team (TRT) set up to help those traumatized by the Omagh bombing on 15 August 1998. Quantitative data were collected using the Compassion Satisfaction/Fatigue Test and the Life Status Review Questionnaire. Qualitative data regarding positive and negative aspects of working with traumatized individuals, as well as caregiver's experience leaving the TRT, were gathered using open‐ended questions contained in the final data set. These questionnaires were completed at four points in time: August 1998, December 1998, August 1999 and February 2001. Ethical approval for the study was gained from the Sperrin Lakeland Trust research committee. Analysis of the quantitative data indicated that levels of compassion fatigue and burnout increased, respectively, from 18.85 to 34.46 and 22.38 to 29.69 over the first year. Levels of compassion satisfaction decreased from 87.62 to 80.15, while levels of satisfaction with life (53.85 to 40.38) and life status (11.23 to 5.62) also decreased. Findings also demonstrated that compassion satisfaction is possibly a protective factor against compassion fatigue and burnout, in that caregivers with high compassion satisfaction scores were less likely to have corresponding high compassion fatigue and burnout scores. Findings from the qualitative data generated, revealed that team spirit and camaraderie, along with the satisfaction of seeing clients recover, were the most positive aspects of working in the team. Media interest, coping with and containing anger shown by bereaved relatives and dealing with the content of client's stories were the most negative. Themes to emerge from leaving the team included lack of understanding and support from non‐trauma managers and an underestimation of the impact on caregivers of finishing in the team. Strategies that were found to be beneficial in helping to alleviate the negative effects of working with trauma were also elicited. This research has implications for practice, management and education.
The perceived expressed emotion in staff scale
Authors: FORSTER J. , FINLAYSON S. , BENTALL R. , DAY J. , RANDALL F. , WOOD P. , REID D. , ROGERS A. , HEALY D.
Published: March 2003

Recent research has highlighted the role of expressed emotion by ward staff in determining the well‐being of psychiatric inpatients. Existing methods of assessing staff expressed emotion involve standardized interviews and are expensive and time‐consuming. We report the development of a questionnaire measure of expressed emotion in staff as perceived by patients. In study 1, factor analysis of items administered to patients in a variety of settings led to the development of a questionnaire with three subscales: supportiveness, criticism and intrusiveness. In study 2, the test–retest reliability of the questionnaire was found to be adequate, and some evidence of concurrent validity for the scale was obtained against expressed emotion rated from staff speech samples. In study 3, the scale was shown to have good concurrent validity against the ward atmosphere scale, and scores were found to be independent of insight or experience of admission to hospital. The perceived expressed emotion in staff scale is a convenient measure, which may have utility for both research and clinical purposes.
The impact on work‐related stress of mental health teams following team‐based learning on clinical risk management
Authors: SHARKEY S. B. , SHARPLES A.
Published: March 2003

Risk management is viewed as a systematic process based on multiprofessional and multi‐agency decision‐making. A learning pack was developed as part of a team‐based learning project aiming to encourage and develop collaborative working practice. This brought different professionals and agencies working in mental health together to learn. There is little doubt that mental health practice is a source of stress for practitioners. Apart from the stress associated with managing ‘risky’ situations, risk management is also a relatively new concept. This can increase stress around ability to cope, both on an individual practitioner level and in teams. This article reports the impact that the learning pack had on team members’ stress, specifically work‐related stress. A range of scales were used to measure change in stress and results demonstrated reduced work‐related pressure in a number of areas following the learning. The implications for team learning in relation to clinical risk management are discussed in light of the findings.
Sleep apnoea in endocrine diseases
Authors: ROSENOW FELIX , McCARTHY VINCENT , CARUSO A.
Published: March 2003

The pertinent literature on the prevalence, clinical manifestations and pathogenic mechanisms of sleep apnoea (SA) in endocrine diseases, namely acromegaly, Cushing syndrome, hypothyroidism and diabetes mellitus was reviewed. An increased prevalence is well documented in patients with active and treated acromegaly. While most authors report peripheral obstruction, due to hypertrophy of tongue and pharyngeal tissues, to be the cause of SA in acromegaly, some findings argue for a role of hormone‐induced changes of central respiratory control. SA is also more common in hypothyroidism, especially when myxedema is present. The associated edema and myopathy appear to be of pathogenic importance. Thyroxin substitution is frequently effective for the treatment of SA but nCPAP can be necessary initially and in some patients even after remission of clinical signs of hypothyroidism. In Cushing disease and syndrome, parapharyngeal fat accumulation can cause SA, but no epidemiological information is available. In non insulin dependent diabetes (NIDDM), obesity is the common risk factor for both, nocturnal hypoxia and insulin resistance. In IDDM, the development of autonomic neuropathy may predispose to SA. Where treatment of the underlying endocrine disease is unable cure the associated SA, nCPAP is usually the treatment of first choice. More prospective studies are clearly needed to establish prevalences and resolve the controversies regarding pathogenesis.
Changes in sleepiness and body temperature precede nocturnal sleep onset: Evidence from a polysomnographic study in young men
Authors: VAN DEN HEUVEL CAMERON J. , NOONE JOSEPH T. , LUSHINGTON KURT , DAWSON DREW
Published: March 2003

Recent research has shown a close temporal relationship between the nocturnal decrease in rectal core temperature and the initiation of sleep. However, there is not yet a clear temporal relationship between changes in peripheral and core temperatures and nocturnal sleep onset. We recorded body temperatures in 14 adult males (age±SEM=22.1±0.6 y), who attended the sleep laboratory for an adaptation night and two counterbalanced experimental sessions. Subjects self‐selected lights‐out on one experimental night (the Habitual Sleep condition). To determine the relationship between body temperature changes and sleep onset, lights out was delayed until after 01.00 hours on the other experimental night (Delayed Sleep condition). Individual datasets in both conditions were expressed relative to the time of sleep onset in the Habitual Sleep condition only, so that they were aligned at identical clock times. Saliva samples confirmed that mean dim light melatonin onset (DLMO) occurred at 00.10±00.16 hours in the Delayed Sleep condition, which was after habitual sleep onset at 23.44±00.08 hours. Rectal core temperature (Tc) decreased significantly over time only in the Habitual Sleep condition ( P
< 0.01). For the 20 min before habitual sleep onset, Delayed Sleep Tc was on average 0.1°C higher than Tc in the Habitual Sleep condition (
P
< 0.01). The greater decline in Habitual Sleep Tc was associated with significantly increased peripheral hand and foot skin temperatures before sleep (both
P
< 0.05). Subjective sleepiness measures were higher in the Habitual Sleep onset condition from 150 min prior until sleep onset (
P < 0.01). From these results it is reasonable to infer that a sequence of thermoregulatory and sleep propensity changes occur before, but are associated with habitual sleep onset, as the changes are significantly attenuated if sleep is delayed.
A dose–response study of total sleep time and the ability to maintain wakefulness
Authors: HÄRMÄ M. , SUVANTO S. , POPKIN S. , PULLI K. , MULDER M. , HIRVONEN K.
Published: March 2003

The apparent connection between sleep debt, performance decrements and workplace accidents has generated a need for feasible vigilance tests that focus on the quantification of daytime sleepiness in occupational settings. The objective of this study was to evaluate the sensitivity of the Maintenance of Wakefulness Test (MWT) to acute sleep deprivation of various doses. Eight healthy female volunteers, mean age 28.9 years (range 23–36), participated in this laboratory study. After an adaptation night, the subjects were assigned to four counterbalanced, randomly ordered night sleep conditions. These four conditions allowed for a time in bed (TIB) of 0, 2, 4 or 8 h, producing a total sleep time of 0, 113, 218 and 427 min, respectively. The ability to sustain wakefulness was measured after the TIB period at 11.00 and 17.00 hours by the MWT. Analysis of variance with repeated measures was used to study the dependence of MWT sleep latencies on the immediately prior TIB period. Both the latency of stage 1 sleep onset and the appearance of slow eye movements reduced significantly with increased sleep loss. The quantitative relationship between the previous total sleep time and the subsequent MWT sleep latencies followed an exponentially decaying function showing a high sensitivity to acute, severe night sleep loss but low sensitivity to less severe sleep restrictions. It is concluded that the MWT seems to be a sensitive method for the estimation of acute sleep deprivation. The test results appear, however, non‐linearly related to the earlier sleep debt.
Sleep fragmentation and daytime vigilance in patients with OSA treated by surgical maxillomandibular advancement compared to CPAP therapy
Authors: CONRADT R. , HOCHBAN W. , HEITMANN J. , BRANDENBURG U. , CASSEL W. , PENZEL T. , PETER J. H.
Published: March 2003

Impaired vigilance is a frequent daytime complaint of patients with obstructive sleep apnoea (OSA). To date, continuous positive airway pressure (CPAP) is a well established therapy for OSA. Nevertheless, in patients with certain craniofacial characteristics, maxillomandibular advancement osteotomy (MMO) is a promising surgical treatment. Twenty‐four male patients with OSA (pretreatment respiratory disturbance index (RDI) 59.3 SD±24.1 events/h) participated in this investigation. The mean age was 42.7±10.7 years and the mean body mass index was 26.7±2.9 kg/m2. According to cephalometric evaluation, all patients had a narrow posterior airway space, more or less due to severe maxillary and mandibular retrognathia. All patients except two were treated first with CPAP for at least 3 months and afterwards by MMO. Two patients only tolerated a CPAP trial for 2 nights. Polysomnographic investigation and daytime vigilance were assessed before therapy, with CPAP therapy and 3 months after surgical treatment. Patients’ reports of impaired daytime performance were confirmed by a pretreatment vigilance test using a 90‐min, four‐choice reaction‐time test. The test was repeated with effective CPAP therapy and postoperatively. Daytime vigilance was increased with CPAP and after surgical treatment in a similar manner. Respiratory and polysomnographic patterns clearly improved, both with CPAP and after surgery, and showed significant changes compared to the pretreatment investigation. The RDI decreased significantly, both with CPAP (5.3±6.0) and postoperatively (5.6±9.6 events/h). The percentages of non‐rapid eye movement Stage 1 (NREM 1) sleep showed a marked decrease (with CPAP 8.2±3.6% and after MMO 8.2±4.4% vs. 13.3±7.4% before treatment), whereas percentages of slow wave sleep increased significantly from 8.0±6.1% before therapy to 18.2±12.8 with CPAP and 14.4±7.3% after MMO. The number of awakenings per hour time in bed (TIB) was significantly reduced after surgery (2.8±1.3), compared to both preoperative investigation (baseline 4.2±2.0 and CPAP 3.4±1.5). Brief arousals per hour TIB were reduced to half with CPAP (19.3±20.0) and after MMO (19.7±13.6), compared to baseline (54.3±20.0). We conclude that the treatment of OSA by MMO in carefully selected cases has positive effects on sleep, respiration and daytime vigilance, which are comparable to CPAP therapy.
Simple reaction time, duration of driving and sleep deprivation in young versus old automobile drivers
Authors: PHILIP P. , TAILLARD J. , QUERA‐SALVA M. A. , BIOULAC B. , ÅKERSTEDT T.
Published: March 2003

Car accidents are one of the major causes of death in modern society and sleepiness is identified as one major risk factor. The purposes of the present study were: (1) to relate the sleep loss and driving time to a performance indicator and (2) to identify risk factors of performance decrement. We investigated 294 drivers (age < 30 years, n=100; age ≥ 30 years, n=194) who drove into a rest stop area. All were asked to fill out a questionnaire about the drive and previous sleep/wake pattern, and to carry out a 10 min, simple reaction time (RT) test. The level of performance is identified by the 10% slowest RTs. Multiple regression analysis, with the mean of the 10% Slowest RTs as the dependent variable, showed that age, duration of drive, and duration (shortness) of previous breaks were the main predictors. Our study suggests that public awareness may need to be raised with respect excessive length of driving, especially in young drivers.
The effects of sleep inertia on decision‐making performance
Authors: Bruck Dorothy , Pisani Danielle L.
Published: March 2003

Sleep inertia, the performance impairment that occurs immediately after awakening, has not been studied previously in relation to decision‐making performance. Twelve subjects were monitored in the sleep laboratory for one night and twice awoken by a fire alarm (slow wave sleep, SWS and REM sleep). Decision making was measured over 10 3‐min trials using the ‘Fire Chief’ computer task under conditions of baseline, SWS and REM arousal. The most important finding was that sleep inertia reduces decision‐making performance for at least 30 min with the greatest impairments (in terms of both performance and subjective ratings) being found within 3 min after abrupt nocturnal awakening. Decision‐making performance was as little as 51% of optimum (i.e. baseline) during these first few minutes. However, after 30 min, performance may still be as much as 20% below optimum. The initial effects of sleep inertia during the first 9 min are significantly greater after SWS arousal than after REM arousal, but this difference is not sustained. Decision‐making performance after REM arousal showed more variability than after SWS arousal. Subjects reported being significantly sleepier and less clear‐headed following both SWS and REM awakenings compared with baseline and this was sustained across the full 30 min. In order to generalize this finding to real‐life situations, further research is required on the effects of continuous noise, emotional arousal and physical activity on the severity and duration of sleep inertia.
Does sleep fragmentation impact recuperation?A review and reanalysis
Authors: Wesensten Nancy Jo , Balkin Thomas J. , Belenky Gregory
Published: March 2003

Studies have shown that next‐day performance and alertness are impaired by sleep fragmentation procedures even when total sleep time (TST) is unaffected. Based on these studies it has been hypothesized that both the duration and continuity of sleep determine its recuperative value. This review of the literature suggests that when sleep fragmentation procedures increase the relative amount of stage 1 sleep, next‐day performance and alertness are impaired. Other studies suggest that stage 1 sleep has little or no recuperative value. Total sleep time, however, is typically defined as the sum of time spent in sleep stages 1, 2, 3, 4, and REM. In the present paper it is shown that when stage 1 sleep is excluded from TST, a stronger relationship between TST and subsequent alertness and performance emerges – and the need to invoke ‘sleep continuity’ as a variable that contributes independently to recuperative sleep processes is obviated. In the same way that partial or total sleep deprivation impairs alertness and performance, it is proposed that sleep disruption also impairs alertness and performance by reducing true recuperative sleep time.
Time in bed, quality of sleep and school functioning of children
Authors: Meijer  , Habekothé  , Van Den Wittenboer
Published: March 2003

This study describes the relationship of time in bed and quality of sleep with concentration and functioning at school. Neurotic and psychosomatic symptoms have been used as control variables. The sample consisted of 449 Dutch children in the seventh and eighth grades of elementary school. The age of the children varied between 9 y 5 mo and 14 y 5 mo. Seven schools participated in the research, with a total of 18 classes. The results indicated that 43% of the children had difficulty getting up in the morning. Furthermore, 15% of the children reported sleep problems and 25% did not feel rested at school. Time in bed and sleep quality show no relationship with concentration. Sleep quality, feeling rested at school and less distinct bedtimes were clearly related to school functioning. Another result was that children who had no difficulty getting up displayed more achievement motivation. Being open to the teacher’s influence and achievement motivation depended mainly on sleep characteristics. Not getting bored at school, self‐image as a pupil and control over aggressive behaviour were also influenced by gender, age, neuroticism and neurosomaticism.
Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity
Authors: Thomas Maria , Sing Helen , Belenky Gregory , Holcomb Henry , Mayberg Helen , Dannals Robert , Wagner JR. Henry , Thorne David , Popp Kathryn , Rowland Laura , Welsh Amy , Balwinski Sharon , Redmond Daniel
Published: March 2003

The negative effects of sleep deprivation on alertness and cognitive performance suggest decreases in brain activity and function, primarily in the thalamus, a subcortical structure involved in alertness and attention, and in the prefrontal cortex, a region subserving alertness, attention, and higher‐order cognitive processes. To test this hypothesis, 17 normal subjects were scanned for quantifiable brain activity changes during 85 h of sleep deprivation using positron emission tomography (PET) and 18Fluorine‐2‐deoxyglucose (18FDG), a marker for regional cerebral metabolic rate for glucose (CMRglu) and neuronal synaptic activity. Subjects were scanned prior to and at 24‐h intervals during the sleep deprivation period, for a total of four scans per subject. During each 30 min 18FDG uptake, subjects performed a sleep deprivation‐sensitive Serial Addition/Subtraction task. Polysomnographic monitoring confirmed that subjects were awake. Twenty‐four hours of sleep deprivation, reported here, resulted in a significant decrease in global CMRglu, and significant decreases in absolute regional CMRglu in several cortical and subcortical structures. No areas of the brain evidenced a significant increase in absolute regional CMRglu. Significant decreases in relative regional CMRglu, reflecting regional brain reductions greater than the global decrease, occurred predominantly in the thalamus and prefrontal and posterior parietal cortices. Alertness and cognitive performance declined in association with these brain deactivations. This study provides evidence that short‐term sleep deprivation produces global decreases in brain activity, with larger reductions in activity in the distributed cortico‐thalamic network mediating attention and higher‐order cognitive processes, and is complementary to studies demonstrating deactivation of these cortical regions during NREM and REM sleep.
Impact of attachment styles on dream recall and dream content: a test of the attachment hypothesis of REM sleep
Authors: McNamara Patrick , Andresen Jensine , Clark Jill , Zborowski Michael , Duffy Cheryl A.
Published: March 2003

We tested the hypothesis (McNamara 1996; Zborowski and McNamara 1998) that dream recall and dream content would pattern with interpersonal attachment styles. In study I, college student volunteers were assessed on measures of attachment, dream recall, dream content and other psychologic measures. Results showed that participants who were classified as ‘high’ on an ‘insecure attachment’ scale were significantly more likely to (a) report a dream, (b) dream ‘frequently’, and (c) evidence more intense images that contextualize strong emotions in their dreams as compared with participants who scored low on the insecure attachment scale. In study II, 76 community dwelling elderly volunteers completed measures of attachment, and dream recall. Participants whose attachment style was classified as ‘preoccupied’ were significantly more likely to report a dream and to report dreams with higher mean number of words per dream as compared with participants classified as ‘securely’ attached or as ‘avoidant’ or as ‘dismissing.’ Dream recall was lowest for the avoidant subjects and highest for the preoccupied subjects. These data support the view that rapid eye movement (REM) sleep and/or dreaming function, in part, to promote attachment.
Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits
Authors: BEEBE DEAN W. , GOZAL DAVID
Published: March 2003

Obstructive sleep apnea (OSA) is accompanied by significant daytime cognitive and behavioral deficits that extend beyond the effects of sleepiness. This article outlines a causal model by which to understand these psychological effects among OSA patients. The model proposes that sleep disruption and blood gas abnormalities prevent sleep‐related restorative processes, and further induce chemical and structural central nervous system cellular injury. This, in turn, leads to dysfunction of prefrontal regions of the brain cortex (PFC), manifested behaviorally in what neuropsychologists have termed `executive dysfunction'. Executive dysfunction is proposed to markedly affect the functional application of cognitive abilities, resulting in maladaptive daytime behaviors. The proposed model (1) accounts for the specific psychological phenotype associated with OSA, (2) accommodates developmental components in this phenotype, (3) bridges between physical and psychological phenomena, (4) suggests mechanisms by which the nocturnal disorder might have effects on daytime functioning, (5) is empirically testable, (6) generates unique research hypotheses, and (7) has practical implications. The model is intended to act as a catalyst for future research and as a preliminary guide for clinicians.
Acute finger temperature changes preceding sleep onsets over a 45‐h period
Authors: Lack Leon , Gradisar Michael
Published: March 2003

A resurgence in the field of sleep initiation and thermoregulation has seen a number of investigators reporting relatively gradual increases in distal skin temperatures of the hands and feet prior to sleep onset at typical bedtimes. The present study extends upon prior knowledge by investigating whether: (1) this is a change of distal skin temperature triggered specifically by the attempt to fall asleep and (2) whether this relationship holds for various phases of the circadian rhythm whenever sleep is attempted. Fourteen healthy good sleepers participated in a modified 45‐h constant routine (CR) with multiple sleep onset latency tests (MSLT) conducted every half hour. After a brief decrease of finger temperature associated with small postural adjustments at the beginning of each sleep latency test, finger temperature showed rapid (0.8 °C min−1) increases of 1–3 °C leading up to the onset of sleep. This rapid increase of finger temperature was relatively consistent across the 45‐h CR, despite very significant circadian variation of the pre‐MSLT baseline finger temperature and homeostatic decrease of sleep latency.
Rapid tryptophan depletion reverses phenelzine‐induced suppression of REM sleep
Authors: Landolt Hans‐Peter , Kelsoe John R. , Rapaport Marc H. , Gillin J. Christian
Published: March 2003

Treatment with the monoamine oxidase inhibitor phenelzine completely suppressed rapid eye movement (REM) sleep in five depressed patients. Hypothesizing that increased serotonergic neurotransmission eliminated REM sleep, we administered a tryptophan‐free amino acid drink (TFD) known to reduce plasma tryptophan and brain levels of serotonin. The TFD reversed the REM sleep suppression, while the control drink (TFD plus tryptophan) had virtually no effect on sleep. Neither TFD nor control drink affected mood, total sleep time, sleep efficiency or the all‐night electroencephalogram power spectra in non‐rapid eye movement (NREM) sleep. We report the first non‐disruptive, double‐blind method for studying human subjects overnight with and without REM sleep. It opens up a novel strategy for investigating the functions of REM sleep, and the roles of serotonin and REM sleep in the regulation of NREM sleep and mood.
Bioavailability of amoxycillin in pigs
Authors: AGERSØ  , FRIIS
Published: March 2003

Amoxycillin was administered to pigs intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.), in a cross‐over design to examine the bioavailability (F) of various drug formulations. These included: a sodium salt for reconstitution in water and administration i.v.; trihydrate salt in an oil base for intramuscular administration producing ‘conventional’ duration of plasma concentrations; a trihydrate salt in oil base giving prolonged (LA) duration, and a trihydrate powder for oral administration in solution. The concentration of amoxycillin in plasma was measured by high‐performance liquid chromatography, and its pharmacokinetic variables were assessed for the individual pigs by use of non‐compartmental methods.

 Following i.v. administration (8.6 mg/kg), amoxycillin was eliminated rapidly with a mean residence time (MRT) of 1.4 h. After i.m. administration of the conventional formulation (14.7 mg/kg), the plasma amoxycillin concentration peaked at 2 h at 5.1 μg/mL. The bioavailability was 0.83. Intramuscular administration (14.1 mg/kg) of the long acting formulation (i.m. LA), lead to two peaks in plasma at 1.3 and 6.6 h. The bioavailability was calculated to be 1.11. After p.o. administration to fasted pigs, peak concentration was reached after 1.9 h, and the bioavailability was 0.33. In fed pigs, the corresponding values were 3.6 h and 0.28. Data showed that treatment of respiratory tract diseases in pigs by p.o. dosing alone, may not be optimal, because of the relatively low bioavailability and the fact that infections often result in reduced feed and water consumption. A rational treatment regime for susceptible respiratory pathogens includes an initial i.m. injection, followed by p.o. dosing every 12 h. Alternatively, the long acting formulation may be administered i.m. in a dose of 15 mg/kg, which would lead to active plasma concentrations for approximately 48 h.
In vitro metabolism of ceftiofur in bovine tissues
Authors: Olson S.C. , Beconi‐Barker M.G. , Smith E.B. , Martin R.A. , Vidmar T.J. , Adams L.D.
Published: March 2003

The metabolism of ceftiofur in bovine kidney, liver, muscle and lung, and the effects of the presence of cystine and glutathione in the media were evaluated using S‐9 and microsomal tissue fractions. Conversion of ceftiofur to desfuroylceftiofur (DFC) was catalyzed by an esterase which was most active in kidney, followed by liver. It was not very active in muscle and lung. After DFC was liberated, it rapidly bound primarily to tissue proteins (>56%), and was also conjugated to cysteine and glutathione. Production of DFC‐cysteine by disulfide exchange of DFC with cystine and production of DFC‐glutathione by conjugation of DFC to glutathione occurred in buffer if glutathione and cystine were present in the medium. These conjugations were also observed in incubations with tissue fractions, indicating that they were not inhibited by the tissues endogenous molecules. In addition, the metabolism of DFC‐glutathione to DFC‐cysteine was observed when tissue proteins were present. The metabolism of DFC‐glutathione to DFC‐cysteine was faster in kidney than in liver. Metabolites devoid of an intact β‐lactam ring were not observed in these in vitro studies.
Ochratoxin A from a toxicological perspective
Authors: Petzinger  , Ziegler
Published: March 2003

Ochratoxin A (OTA) is a widespread mycotoxin which is produced mainly by the mould fungi Aspergillus ochraceus and Penicillum verrucosum during the storage of cereals, cereal products and other plant‐derived products such as herbs, spices, grapes, etc. By carry over from mouldy fodder, ochratoxin A is also found in pork meat, offal and sausages containing pork blood. When ingested as a food contaminant, OTA is very persistent in human beings with a blood half‐life of 35 days after a single oral dosage due to unfavourable elimination toxicokinetics. This renders the toxin among the most frequent mycotoxin contaminants in human blood in the EU, the US, Canada, and elsewhere, where it has been investigated. OTA is neither stored nor deposited in the body, but heterogeneous body distribution may impose serious damage to the kidneys. The toxin was classified a 2B cancer compound, being possibly carcinogenic for humans. It was among the strongest carcinogenic compounds in rats and mice. As the toxicological profile also includes teratogenesis, nephrotoxicity, and immunotoxicity, legislation authorities are currently discussing maximal residue levels (MRL) for OTA in various foodstuffs. In the present article arguments are presented which suggest an acceptable daily intake (ADI) of 1.5 ng OTA/kg body weight and a much lower MRL than 5 μg OTA/kg cereals and cereal products as has been postulated by the EU commission.
Single‐dose pharmacokinetics of flumequine in cod (Gadus morhua) and goldsinny wrasse (Ctenolabrus rupestris)
Authors: Hansen M. K. , Horsberg T. E.
Published: March 2003

Knowledge of the pharmacokinetic properties of drugs to combat bacterial infections in cod (Gadus morhua) and wrasse (Ctenolabrus rupestris) is limited. One antimicrobial agent likely to be effective is flumequine. The aim of this study was to investigate the pharmacokinetic properties of flumequine in these two species.

Flumequine was administered intravenously to cod (G. morhua) at a dose of 5 mg/kg bodyweight and wrasse (C. rupestris) at a dose of 10 mg/kg. Flumequine was also administered orally to both species at a dose of 10 mg/kg body weight, and as a bath treatment at a dose of 10 mg/L water for 2 h. Identical experimental designs were used otherwise. The study was performed in seawater with a salinity of 3.2% and a temperature of 8.0±0.2 °C (cod) and 14.5±0.4 °C (wrasse). Pharmacokinetic modelling of the data showed that flumequine had quite different pharmacokinetic properties in cod and wrasse. Following intravenous administration, the volumes of distribution at steady‐state (Vss) were 2.41 L/kg (cod) and 2.15 L/kg (wrasse). Total body clearances (Cl) were 0.024 L/h.kg (cod) and 0.14 L/h.kg (wrasse) and the elimination half‐lives (t1/2 λ z) were calculated to be 75 h (cod) and 31 h (wrasse). Mean residence times (MRT) were 99 h (cod) and 16 h (wrasse). Following oral administration, the t1/2 λ z were 74 h (cod) and 41 h (wrasse). Maximal plasma concentrations (tmax) were 3.5 mg/L (cod) and 1.7 mg/L (wrasse), and were observed 24 h post‐administration in cod and 1 h post‐administration in wrasse. The oral bioavailabilities (F) were calculated to be 65% (cod) and 41% (wrasse). Following bath administration, maximal plasma concentrations were 0.13 mg/L (cod) and 0.09 mg/L (wrasse), and were observed immediately after the end of the bath.
Feasibility of interspecies extrapolation in determining the bioequivalence of animal products intended for intramuscular administration
Authors: Martinez M. N. , Pedersoli W. M. , Ravis W. R. , Jackson J. D. , Cullison R.
Published: March 2003

To examine the validity of extrapolating parenteral product bioequivalence determinations across target animal species, the relative bioavailability of two injectable formulations of ampicillin trihydrate (PolyflexR, a water‐based suspension, and Ampi‐kel 10R, an oil‐based suspension) was examined in calves, sheep and swine. Employing products recognized to be bioinequivalent provided an opportunity to explore potential species‐by‐formulation interactions. As compared with PolyflexR, Ampi‐kel 10R exhibited lower area under the curve (AUC) estimates but higher peak concentrations in all target animal species. Nevertheless, marked interspecies differences were noted in the width and bounds of the confidence intervals about the differences in treatment means. Potential physiological and physico‐chemical reasons for these findings are discussed.
Veterinary pharmacovigilance: between regulation and science
Authors: Keck G. , Ibrahim C.
Published: March 2003

Veterinary pharmacovigilance has shown a remarkable development in recent years. After presenting briefly the regulatory context, this paper considers the scope of veterinary pharmacovigilance, causality assessment of suspected adverse drug reactions (ADRs), the systems existing in different countries and the evolution for the coming years. The involvement of veterinary research and teaching institutions should certainly become more important in this cross‐road activity.
Serum pharmacokinetics and tissue and milk residues of oxytetracycline in goats following a single intramuscular injection of a long‐acting preparation and milk residues following a single subcutaneous injection
Authors: PAYNE M. A. , BABISH J. G. , BULGIN M. , LANE M. , WETZLICH S. , CRAIGMILL A. L.
Published: March 2003

Separate groups of goats were used to determine drug depletion patterns in serum (n=10), tissue (n=20) and milk (n=8) following a single intramuscular (i.m.) dose of 20 mg/kg of a long‐acting oxytetracycline (OTC) formulation (Liquamycin® LA‐200®). Milk residues were also determined following a subcutaneous (s.c.) administration of the same product at the same dose. Serum samples were taken for 24 h post‐treatment and tissues (fat, liver, kidney, muscle and injection site) collected at 4, 7, 14, 21 and 28 days following injection. Milk from lactating goats was collected every 12 h for 8 days following both the i.m. and s.c. treatments utilizing an intervening 5‐week washout period. Residues in serum and tissue were measured using a microbial inhibition assay, while milk residues were measured using both a microbial inhibition assay and a validated HPLC method. The serum pharmacokinetic parameters of OTC in goats were determined, with a mean AUC=67.4 μg h/mL, mean terminal half‐life=14.4 h, and apparent clearance=0.33 L/kg h. Tissue half‐lives could not be determined with confidence because the collection times provided only two points at which residues could be measured for most tissues. Oxytetracycline residues in all goat tissue samples measured less then cattle tissue tolerance by 96 h postdosing. One‐compartment model describing milk depletion data for i.m. and s.c. dosing had terminal slope half‐lives of 20.1 and 36.1 h, respectively. By 96 h post‐treatment none of the milk samples contained OTC residues in excess of the cattle milk tolerance (0.3 p.p.m.). For both milk and tissue, the upper‐bound 99% confidence intervals for the samples taken from goats 96 h postdosing were lower than approved cow milk and tissue tolerances.
Multi‐measurement method comparison of three commercial hepatitis B virus DNA quantification assays
Authors: Krajden M. , Minor J. , Cork L. , Comanor L.
Published: March 2003

Serum specimens (327) from patients with chronic hepatitis B were evaluated for hepatitis B virus (HBV) DNA using three commercial assays – Chiron Quantiplex™ (CA), Digene Hybrid Capture (DA) and Abbott HBV DNA assay (AA). The HBV DNA values obtained following evaluation were used to compare the linearity, responsiveness and precision of each assay and to determine the conversion between the three different assay values. The comparison was accomplished using a new statistical approach termed the multi‐measurement method (MMM). MMM is a minimal bias, non‐linear regression technique that allows simultaneous multiassay performance evaluation as well as assay value interconversion. MMM analysis demonstrated that the CA was more sensitive and responsive than either the DA or the AA. Both the CA and DA were more precise than the AA. Validation of the MMM results was performed using two additional data sets of 551 and 100 specimens, respectively. MMM is a novel statistical tool that has a broad application for the generation of statistically normalized laboratory data and for interassay standardization.
Evaluation of twice‐daily administration of interferon‐β for chronic hepatitis C
Authors: Kakizaki S. , Takagi H. , Yamada T. , Ichikawa T. , Abe T. , Sohara N. , Kosone T. , Kaneko M. , Takezawa J. , Takayama H. , Nagamine T. , Mori M.
Published: March 2003

To improve the efficacy of interferon (IFN) in the treatment of chronic hepatitis C, administration of IFN‐β twice per day was evaluated. Thirty‐eight patients with chronic hepatitis C (26 males and 12 females, aged 25–67 years) were included. Patients were treated with a new protocol that included twice‐daily treatment with IFN‐β. Three million units (MU) of IFN‐β was administered twice daily every day for 4 weeks followed by 10 MU of IFN‐α2b, every day for 2 weeks and then three times a week for 18 weeks (total IFN‐β, 148 MU; IFN‐α2b, 680 MU). Complete responders (CR) were defined by alanine aminotransferase levels that normalized within 6 months after completion of IFN therapy and remained normal for more than 6 months, and by serum hepatitis C virus (HCV) RNA levels that became negative as determined using the Amplicor® assay. Twenty‐one of 38 (55.3%) patients were CR. Nine of 21 (42.9%) patients with HCV serotype 1 were responders compared with nine of 12 (75.0%) patients with HCV serotype 2. In patients with an HCV titre greater than 1 million equivalents ml–1 (1 MEq ml–1), nine of 24 (37.5%) responded, and in patients with HCV titres less than 1 MEq ml–1, 12 of 14 (85.7%) responded. In patients with HCV serotype 1 and greater than 1 MEq ml–1 HCV RNA, four of 15 (26.7%) responded to IFN. Two‐thirds (66.7%) of the patients who became negative for HCV RNA after 2 weeks of therapy responded, while 72.7% of those with positive HCV RNA after 2 weeks of therapy were non‐responders. Proteinuria was frequently observed as an adverse effect of twice‐daily administration of IFN‐β. The combination of twice‐daily administration of IFN‐β for 4 weeks followed by IFN‐α showed a high response rate in patients with chronic hepatitis C, but in patients with both serotype 1 and a high titre of HCV RNA, response rates were still low. Thus, the HCV RNA titre 2 weeks after starting therapy with IFN was useful for predicting the eventual response to IFN.
Retrospective serological analysis of hepatitis E patients: a long‐term follow‐up study
Authors: Chadha M. S. , Walimbe A. M. , Arankalle V. A.
Published: March 2003

The aim of this study was to evaluate the persistence and protective role of antibodies to hepatitis E virus (anti‐HEV) after natural hepatitis E infection. A retrospective analysis of immunoglobulin G (IgG) anti‐HEV was performed in 37 patients followed‐up for 5 years after epidemics of HEV. Two patients with sporadic hepatitis E (HE) were followed‐up for 12 and 8 years. All patients infected during epidemics of HE were positive for IgG anti‐HEV at 5 years of follow‐up (geometric mean titre: 174.75). The two patients with sporadic HE were positive for IgG anti‐HEV at the end of 12 and 8 years of follow‐up (the IgG anti‐HEV titre was 1 : 200 in each patient). This study showed protection against disease by antibodies to HEV. It was therefore concluded that hepatitis E may be preventable by an efficacious vaccine.