bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of occlusal appliance therapy in patients with temporomandibular disorders of mainly myogenous pain. A randomized controlled trial in a short‐term perspective
Authors: EKBERG E. , NILNER M. , VALLON D.
Published: March 2003

Aim:  In a randomized controlled trial investigate the short‐term effect of treatment with stabilization appliance compared with a control appliance in patients with temporomandibular disorders (TMD) of mainly myogenous pain.

Material and methods:  Out of 926 referrals to the Department of Stomatognathic Physiology in Malmö for treatment of TMD during 2 years, 338 patients were clinically screened for possible participation in the study. Patients with mainly myogenous pain were selected from the original group of 926 patients. Sixty TMD patients with mainly myogenous pain were allocated at random into two equally sized groups: (T) treatment group given a stabilization appliance; (C) control group given a control appliance. The study was performed as a randomized controlled trial and comprised four visits. At the last visit, after 10 weeks of treatment with occlusal appliance, the treatment outcome was evaluated.

Results:  There was a significant reduction of changes in overall severity of pain, reported pain during mandibular movements and reduction of changes in severity of headache in the treatment group compared with the control group. There was also a significant decreased number of tender masticatory muscles in the treatment group compared with the control group.

Conclusion:  The results of this short‐term evaluation suggest that the stabilization appliance is effective in the alleviation of symptoms and signs in TMD patients of mainly myogenous pain. The stabilization appliance can therefore be recommended for TMD patients of mainly myogenous pain.
Cellular reactions to polylactide‐based sponge and collagen gel in subcutaneous tissue
Authors: Taira M. , Araki Y. , Nakao H. , Takahashi J. , HYON S.‐H. , Tsutsumi S.
Published: March 2003

summary  Polylactide copolymer and collagen are now used as bio‐absorbable scaffold materials for restoration of lost oral tissues. Polylactide caprolactone (PLCL) sponge and collagen gel were examined for their cellular reactions when implanted in 8‐week‐old Sprague–Dawley (SD) rats’ subcutaneous tissues for up to 8 weeks. The PLCL sponges were slowly absorbed by a mild chronic inflammation process in which multinucleated giant cells covered and slowly captivated the sponge surfaces without thick encapsulation. On the other hand, collagen gel was surrounded by thick inflammatory reaction zones and infiltrated by acute inflammation cells including neutrophils, lymphocytes and macrophages, and disappeared more rapidly. Although the bio‐absorption process differed, both materials, when combined, appear to be useful scaffold materials for tissue engineering therapy in future dental practice.
The periodontal status of pregnant women and its relationship with socio‐demographic and clinical variables
Authors: Taani D. Q. , Habashneh R. , Hammad M. M. , Batieha A.
Published: March 2003

summary  The aims of this study were to assess the periodontal health and oral hygiene status of pregnant women and non‐pregnant controls and to evaluate the effect of socio‐demographic and other variables on such periodontal status. A total of 400 women, of whom 200 were pregnant (mean age=30 years, s.e.m.=0ḃ05) and 200 non‐pregnant controls (mean age=32 years, s.e.m.=0ḃ05) were chosen at random from four health centres. The clinical parameters used were the Silness and Loe plaque index (Pl.I), Loe and Silness gingival index (GI), probing pocket depth (PPD), probing attachment level (PAL), any relationship to socio‐demographic (age, level of education and professional level) and clinical variables (gestation period, previous pregnancy and vomiting during pregnancy) was evaluated. The results showed that pregnant women had significantly higher GI and PPD scores (P < 0ḃ005) but with no statistically significant differences in PAL or Pl.I (P > 0ḃ01) compared with non‐pregnant controls. Increased age, lower level of education and non‐employment were associated with significantly higher GI and PPD scores (P < 0ḃ01). All these clinical parameters increased in parallel with the increase in the stage of pregnancy, reaching their maximum at the eighth month. Women with previous or multiple pregnancy had statistically significantly higher GI and PPD scores than those who were pregnant for the first time (P < 0ḃ01), but with no statistically significant differences in Pl.I or PAL scores (P > 0ḃ05). Also, women who vomited during pregnancy had significantly higher GI and PPD scores compared with those who did not vomit (P < 0ḃ05). It is concluded that gingival inflammatory symptoms are aggravated during pregnancy and are related to increased age, lower level of education and non‐employment. Therefore periodontal preventive programmes are very important for pregnant women.
‘We're doing it already …’: adult protection in mental health services
Authors: Brown  , Keating
Published: March 2003

This paper explores the implementation of generic adult protection policies in mental health services, both in terms of conceptual issues about the nature and thresholds of abuse which are identified and/or tolerated within different settings, and in relation to existing structures for working on risk assessment, such as the Care Programme Approach and Supervised Discharge. The paper asks if resistance from mental health workers to new adult protection procedures reflects a reality that they have ‘been doing it already’ or whether there is a deeper resistance to acknowledgement of abuse issues in the lives of service users, and to the burden which such knowledge places on workers who are already stretched to the limit.
The meaning of caring for patients on a long‐term psychiatric ward as narrated by formal care providers
Authors: Pejlert  , Asplund  , Gilje  , Norberg
Published: March 2003

Seventeen care providers were interviewed about their caring experiences on a hospital psychiatric ward. The interviews focused on the meaning of their work, including the care they provide and the nature of the patient as a person. The study was guided by a phenomenological hermeneutic perspective inspired by Ricoeur (1976). The analysis focused on context and form. Three themes illuminate the meaning of care provided. These themes are as follows; being in the midst of human storage, moving towards a human care of relations, and struggling with ‘the old’ and ‘the new’. Experiencing work as being in the midst of a human storage reflects the historical and human situation of warehousing psychiatric patients. The care providers are experiencing a shift in their view of the patient and the meaning of their work, towards a more human care of relations. For these care providers, there is a struggle between the past, the present and the future. This struggle between ‘the old’ and ‘the new’ conveys a struggle between doing as a nurse, which dominates the past, and relating, which is, or needs to be, the current and future focus in psychiatric care. The shift in view distinguished itself by the care providers viewing the patient as being vulnerable and having problems with relations. The results have been interpreted and discussed in the light of a previously published interview study with the patients, carried out at the same time on the same ward. Attending to ingrained attitudes of the past and their influence on new approaches to care is essential to understanding not only changes in ways of doing nursing tasks, but also ways of relating.
Caregiver‐assisted music events in psychogeriatric care
Authors: Götell E. , Brown S. , Ekman S.‐L.
Published: March 2003

An ethnographic approach to the study of caregiver‐assisted music events was employed with patients suffering from dementia or suspected dementia. The aim of this study was to illuminate the importance of music events and the reactions and social interactions of patients with dementia or suspected dementia and their caregivers before, during and after such events, including the remainder of the day. The results showed that the patients experienced an ability to sing, play instruments, perform body movements, and make puns during such music events. While singing familiar songs, some patients experienced the return of distant memories, which they seemed to find very pleasurable. During and after the music events, the personnel experienced bonding with the patients, who seemed easier to care for. Caregiver‐assisted music events show a great potential for use in dementia care.
The perceptions and aspirations illicit drug users hold toward health care staff and the care they receive
Authors: Mclaughlin D. F. , Mckenna H. , Leslie J. C.
Published: March 2003

Over the 30 years of conflict, Northern Ireland escaped the worst excess of illegal drug trafficking and usage. However, the recent ‘peace dividend’ has brought with it an unprecedented rise in the availability and use of illicit drugs. With this, new problems and pressures have been brought to bear on the health service. The literature would suggest that drug users are loathed and feared by health care staff. Staff will also admit to be lacking in the knowledge and skills necessary for the delivery of appropriate support and treatment for this client group. Further, the literature has little to offer on the experiences and aspirations of drug users in relation to their treatment and the staff who care for them. In order to understand the drug users’ experiences of health care and health staff, focus group methodology was employed to obtain qualitative data. A total of 20 illicit drug users from across Northern Ireland took part. Supporting the literature, all had experienced ‘care’ that they felt was filled with judgement, hostility and loathing. They recognized clearly the challenge they pose to health care staff. These findings indicate that there is obvious dissonance between those tasked to care for drug users and drug users themselves, with little respect being shown on either side. Results suggest that action needs to be taken to address the deficits in the knowledge, skills and values of health care professionals in relation to illicit drug users. The findings will be of interest to service providers within and outside the United Kingdom.
Seeking a clarification of meaning: a phenomenological interpretation of the craft of mental health nursing
Authors: Graham I. W.
Published: March 2003

This paper gives a description of mental health nursing practice provided by nurses working in a community mental health resource centre, in an inner city area of a northern English city. The centre offered a mental health service for a mixed client group who had enduring and/or acute mental health problems. The nurses engaged as the subjects in a phenomenological study of the nature and meaning of their practice in order to improve the care they gave the clients. The findings from the study suggest that, for the nurses, the meaning of nursing was characterized by holism, relationship‐building, partnership and empowerment. The findings revealed that the aim of nursing was to promote a positive self‐concept in clients and this was achieved by exploring the lived experience of the client and the nurse through relationship‐building processes.
Trauma for all: a pilot study of the subjective experience of physical restraint for mental health inpatients and staff in the UK
Authors: Bonner G. , Lowe T. , Rawcliffe D. , Wellman N.
Published: March 2003

Violence and aggression is common in psychiatric inpatient units. Despite the near universal prevalence of restraint, there is very little published research on either the efficacy or the subjective effects of restraint on staff or patients. In this pilot study, semistructured interviews were given to the patients and staff involved in six untoward incidents in which the patient participant had been subject to manual physical restraint. Participants were interviewed as soon as possible after the occurrence of the incidents. The interviews asked the patient and staff participants to identify and discuss the factors that they found helpful and unhelpful during and in the immediate aftermath of these incidents. The incidents generated strong emotions for all concerned. The patients valued staff time and attention but felt that they received too little attention. Both nurses and patients discriminated between permanent and temporary staff. Patients reported feeling upset, distressed and ignored prior to the incidents and isolated and ashamed afterwards. Postincident debriefing was valued by all but was patchy for staff and rarer still for patients. Patients feared the possibility of being restrained. Half of the patients and several staff members reported that the incidents had reawakened distressing memories of previous traumatic events. Further research on the subjective effects of restraint is urgently needed.
Dialogism in action: talking fact and fiction
Authors: Durgahee T.
Published: March 2003

Mental health is maintained through our discourse with society. Whether one talks fact or fiction, it is not only a mode of expression but also a way of constructing reality as perceived by those suffering from psychiatric problems. Therefore, what a mentally ill person says has meaning although it may not seem so to the carers. In this study, seven patients’ dialogic journals, used for capturing their thoughts during their illness over a period of 8 months, are critically analysed. The writing shows that writing can help patients to (i) have a personal conversation to make sense of what is happening to them, (ii) assess whether fact or fiction is at work, (iii) keep flow or lack of ideas in context, instead of ‘being confused’ and (iv) value the dialogic journal as a tool for emancipation.
Philosophy, care and treatment on the psychiatric intensive care unit: themes, trends and future practice
Authors: CROWHURST N. , BOWERS L.
Published: March 2003

Psychiatric intensive care units (PICUs) were first developed in the UK in the early 1970s and have become an integral part of inpatient services. This paper reviews all aspects of PICU provision from its origins to the most recent studies of intensive care treatment and philosophy. A search of CINAHL, MEDLINE and British Nursing Index databases revealed ample research and discussion papers from the past 30 years to permit a thorough review of the available literature. This divides roughly into discussion and descriptive research on topics related to: (a) the infrastructure of PICUs, including bed numbers, staffing levels, admission criteria and aspects of the physical environment; and (b) the treatment provided to patients on the PICU, both pharmacological and psychosocial, plus a limited amount of evaluative research on the efficacy of PICU care. This paper provides a summary and overview of these issues based upon currently available literature. It concludes that there is strong evidence for wide variation in the provision and nature of PICU care, reflecting idiosyncratic and localized development of services. Moreover, there is an almost complete lack of evidence on the efficacy of PICU care for particular types of patients and problems, leaving a paucity of research upon which PICU infrastructure, policy and therapeutic approach can be based.
Sleep loss impairs short and novel language tasks having a prefrontal focus
Authors: HARRISON YVONNE , HORNE JAMES
Published: March 2003

Most cognitive tests administered during sleep loss are well rehearsed to remove practice effects. This can introduce tedium and a loss of novelty, which may be the key to the test's subsequent sensitivity to sleep loss, and why it may need only a few minutes administration before sleep loss effects are apparent. There is little evidence to show that any of these tests are actually affected by sleep loss if given de novo, without practice, but using a non‐sleep deprived control group. Although the sleep deprivation literature advocates that short, novel and stimulating tests would not be expected to be sensitive to sleep loss, recent sleep loss findings using neuropsychological tests focussing on the prefrontal cortex, indicate that such tests may challenge this maxim. Twenty healthy young adults were randomly assigned to two groups: nil sleep deprivation (control), and 36h continuous sleep deprivation (SD). Two, novel, interesting and short (6 min) language tests, known (by brain imaging) to have predominantly a PFC focus, were given, once, towards the end of SD: (i) the Haylings test – which measures the capacity to inhibit strong associations in favour of novel responses, and (ii) a variant of the word fluency test – innovation in a verb‐to‐noun association. Subjects were exhorted to do their best. Compared with control subjects both tasks were significantly impaired by SD. As a check on the effects on the Haylings test, a repeat study was undertaken with 30 more subjects randomly divided as before. The outcome was similar. Linguistically, sleep loss appears to interfere with novel responses and the ability to suppress routine answers.
Centralis superior raphe, reticularis pontis nuclei, and sleep‐wakefulness cycle in cats
Authors: ARPA JAVIER , PADRINO CARMEN , RODRÍGUEZ‐ALBARIÑO APOLINAR , DE ANDRÉS ISABEL
Published: March 2003

This study examines the influence of lesions in the centralis superior raphe nucleus (CeSR) and adjacent paramedial pontine tegmentum on the sleep/wakefulness cycle (SWC) in cats. Sixteen cats had electrodes implanted for electro‐oculogram (EOG), electromyogram (EMG), electroencephalogram (EEG) and ponto‐geniculo‐occipital (PGO) recordings. There were 10 experimental animals: seven animals received diathermocoagulation lesions destroying between 7 and 27% of the CeSR; the remaining three cats suffered bilateral lesions in the paramedial portion of the reticularis pontis oralis (RPO) and caudalis (RPC) nuclei. Six sham‐operated animals were used as controls. Recordings were taken of all animals in continuous 23‐h sessions once a week for 12 weeks. Results indicated that the threshold for SWC state changes (increase of wakefulness (W) and drowsiness (D), and decrease of slow wave sleep (SWS)) after CeSR lesion is approximately 11.3% following volumetric destruction of the nucleus. The amount of CeSR damage (CeSR‐D) only correlated significantly with the amount of W (positive correlation) and SWS (negative correlation) during the first week post‐lesion. The changes in W over the course of the study were different in the two experimental groups. In both groups, total W was increased with respect to the controls, however, these increases were observed earlier in the CeSR‐D group. The return to near control values in SWC state over days 15–28 of the study does not represent a definitive recovery by the CeSR‐D cats. All the SWC states returned to control values by the tenth week in the cats with paramedial reticular pontine damage.
Molecular approaches towards the isolation of sleep‐related genes
Authors: Schibler  , Tafti
Published: March 2003

Behavioural genetics is one of the most enticing fields in modern biology. Owing to straightforward and semiautomated techniques that can be used to measure locomotor activity, circadian rhythmicity is perhaps the best studied behaviour in animals. Thus, during the past decade, five essential circadian clock genes have been isolated in Drosophila, and homologous counterparts for all of these genes have also been found in mammals. As the sleep–wake cycle is under the control of the circadian clock, these circadian master genes are expected to influence sleeping behaviour. However, different vigilance states are regulated by additional mechanisms that also have a genetic basis. In this article we discuss molecular approaches that may prove useful in the search for sleep‐related genes.
Prediction of sleep‐disordered breathing by unattended overnight oximetry
Authors: OLSON L. G. , AMBROGETTI A. , GYULAY S. G.
Published: March 2003

Between January 1994 and July 1997, 793 patients suspected of having sleep‐disordered breathing had unattended overnight oximetry in their homes followed by laboratory polysomnography. From the oximetry data we extracted cumulative percentage time at SaO2 < 90% (CT90) and a saturation variability index (ΔIndex, the sum of the differences between successive readings divided by the number of readings – 1). CT90 was weakly correlated with polysomnographic apnea/hypopnea index (AHI), (Spearman 𝓅=0.36, P< 0.0001) and with ΔIndex (𝓅=0.71, P< 0.0001). ΔIndex was more closely correlated with AHI (𝓅=0.59, P< 0.0001). In a multivariate model, only ΔIndex was significantly related to AHI, the relationship being AHI=18.8 ΔIndex +7.7. The 95% CI for the coefficient were 16.2, 21.4, and for the constant were 5.8, 9.7. The sensitivity of a ΔIndex cut‐off of 0.4 for the detection of AHI≥15 was 88%, for detection of AHI≥20 was 90% and for the detection of AHI≥25 was 91%. The specificity of ΔIndex ≥0.4 for AHI≥15 was 40%. In 113 further patients, oximetry was performed simultaneously with laboratory polysomnography. Under these circumstances ΔIndex was more closely correlated with AHI (𝓅=0.74, P< 0.0001), as was CT90 (𝓅=0.58, P< 0.0001). Sensitivity of ΔIndex ≥0.4 for detection of AHI≥15 was not improved at 88%, but specificity was better at 70%. We concluded that oximetry using a saturation variability index is sensitive but nonspecific for the detection of obstructive sleep apnea, and that few false negative but a significant proportion of false positive results arise from night‐to‐night variability.
Strong rebound of wakefulness follows prostaglandin D2‐ or adenosine A2a receptor agonist‐induced sleep
Authors: Gerashchenko Dmitry , Okano Yasuhisa , Urade Yoshihiro , Inoué Shojiro , Hayaishi Osamu
Published: March 2003

We studied the effect of sleep excess on the sleep‐wakefulness pattern of rats. Subarachnoid infusion of prostaglandin D2 or the adenosine A2a receptor agonist CGS21680 effectively induced slow wave sleep (SWS) for the first 12 h of the night‐time period, whereas they did not induce sleep during the following 24 h of infusion. An increase in the amount of wakefulness was seen during the last 12 h of prostaglandin D2 infusion. The amounts of wakefulness strongly increased during the following 36‐h recovery period. Rebound wakefulness was extraordinarily strong after the cessation of CGS21680 infusion, reaching almost complete insomnia during the night‐time. Treatment of animals with prostaglandin D2 overnight, following by treatment with CGS21680 on the next night, resulted in the strongest induction of wakefulness rebound. During the rebound period, the amount of wakefulness reached up to 50 min per hour in the daytime. Rebound of wakefulness depended on the amounts of preceding SWS induced by infusion of prostaglandin D2 for 6 or 12 h and of CGS21680 for 12 h. The larger the amount of SWS, the larger the amount of the following rebound of wakefulness. Rebounds of wakefulness occurred as a result of decrease in SWS amounts, whereas paradoxical sleep amounts did not change. Desensitization of adenosine A2a receptors and accumulation of prostaglandin E2 may be involved in the production of strong wakefulness rebound following relatively long treatments (more than 12 h) with prostaglandin D2 or CGS21680.
Effects of amphetamine and modafinil on the sleep/wake cycle during experimental hypersomnia induced by sleep deprivation in the cat
Authors: Lin J. S. , Gervasoni D. , Hou Y. , Vanni‐Mercier G. , Rambert F. , Frydman A. , Jouvet M.
Published: March 2003

Modafinil is a newly discovered waking substance now being used in the treatment of hypersomnia and narcolepsy. We have shown previously in the cat that, unlike amphetamine, modafinil induces long‐lasting wakefulness (W) without behavioral excitation and subsequent sleep rebound, and that its waking effect does not depend on endogenous catecholamines. To further characterize the awakening properties of modafinil and current psychostimulants in experimental models of hypersomnia, we examined the effect of oral administration of placebo, modafinil (5 mg kg−1) or amphetamine (1 mg kg−1) on the sleep/wake cycle and power spectral density (PSD) in cats after an 18‐h water‐tank sleep deprivation period. We found that the placebo had no effect on the dynamics of sleep recovery, while both modafinil and amphetamine induced suppression of cortical slow activity and a waking state lasting 6–8 h. After the amphetamine‐induced waking period, both deep slow wave sleep (SWS2) and paradoxical sleep (PS) occurred in greater amounts than after placebo and the PSD during SWS was also increased. Thus, the cumulative time spent in W during a 48‐h period was similar to that with placebo, indicating enhanced sleep rebound. In contrast, after the modafinil‐induced W, the occurrence and evolution of SWS2 or PS, as well as the PSD during SWS, were similar to those seen with placebo during the same period, so that the total time spent in W in a 48‐h period remained significantly higher than the control level, indicating no additional sleep rebound. These results indicate that modafinil is effective against somnolence and hypersomnia and does not produce a subsequent increase in sleep and suggest that the pharmacological profile of modafinil is different from that of amphetamine.
The relationship between frequency of rapid eye movements in REM sleep and SWS rebound
Authors: De Gennaro Luigi , Ferrara Michele , Bertini Mario
Published: March 2003

Previous studies have shown a decrease in rapid eye movement (REM) frequency during desynchronized sleep in recovery nights following total or partial sleep deprivation. This effect has been ascribed to an increase in sleep need or sleep depth consequent to sleep length manipulations. The aims of this study were to assess REM frequency variations in the recovery night after two consecutive nights of selective slow‐wave sleep (SWS) deprivation, and to evaluate the relationships between REM frequency and SWS amount and auditory arousal thresholds (AAT), as an independent index of sleep depth. Ten normal males slept for six consecutive nights in the laboratory: one adaptation, two baseline, two selective SWS deprivation and one recovery night. SWS deprivation allowed us to set the SWS amount during both deprivation nights close to zero, without any shortening of total sleep time. In the ensuing recovery night a significant SWS rebound was found, accompanied by an increase in AAT. In addition, REM frequency decreased significantly compared with baseline. This effect cannot be attributed to a variation in prior sleep duration, since there was no sleep loss during the selective SWS deprivation nights. Stepwise regression also showed that the decrease in REM frequency is not correlated with the increase in AAT, the traditional index of sleep depth, but is correlated with SWS rebound.
Between‐sleep states transitions in premature babies
Authors: Curzi‐Dascalova Lilia
Published: March 2003

To assess the manner in which between‐sleep state transitions occur in infants, we examined polysomnography (PSG) studies in 25 clinically and neurologically normal, appropriate‐for‐gestational‐age, 30‐to‐36‐week‐gestational age (GA) infants. Twenty infants underwent paper PSG and five infants digitised PSG. Sleep states were coded based on concordance of REMs and the electroencephalogram (EEG) pattern. Data were analysed using a multivariate linear model, with the subject factor as a cluster. Duration of active sleep (AS) to quiet sleep (QS) transitions (median 4.8 min) was significantly longer than duration of QS to AS transitions (1.7 min) and was independent from GA and from the recording method (paper vs. digitized PSG). The sequence of modifications in parameters (REM and EEG) was invariable: REM cessation was the first change in AS to QS transitions, and REM appearance was the last change in the QS to AS transitions. Our study demonstrates a stable, well‐organized pattern of between‐sleep‐states transitions in healthy 30‐to‐36‐week GA premature infants. These findings are similar to those described in full‐term new‐borns and are in agreement with our previous observations of well‐defined sleep states at the age investigated here.
A sleep diary and questionnaire study of naturally short sleepers
Authors: Monk Timothy H. , Buysse Daniel J. , Welsh David K. , Kennedy Kathy S. , Rose Lynda R.
Published: March 2003

Whereas most people require more than 6 h of sleep to feel well rested, there appears to be a group of people who can function well on between 3 and 6 h of sleep. The aims of the present study were to compare 12 naturally short (3–6 h) sleepers (9 males 3 females, mean age 39.6 years, SD age 10.1 years) recruited by a media publicity campaign with age, gender and chronotype matched medium length (7–8.5 h) sleepers on various measures. Measurement instruments included diaries and questionnaires to assess sleep duration and timing, as well as questionnaire assessments of sleep pathology, morningness–eveningness, extroversion, neuroticism, pathological daytime sleepiness, subclinical hypomania, optimism, depressive symptoms, exercise, and work habits. Few measures showed reliable differences between naturally short sleepers and controls except the obvious ones related to sleep duration. There was, however, some evidence for subclinical hypomanic symptoms in naturally short sleepers.
Clinical and polysomnographic characteristics of 34 patients with Kleine–Levin syndrome
Authors: Gadoth Natan , Kesler Anat , Vainstein Gabriel , Peled Ron , Lavie Peretz
Published: March 2003

There is only scant information on sleep characteristics and long‐term follow‐up in patients with Kleine–Levin syndrome (KLS). This study describes the clinical course, results of polysomnography and long‐term follow‐up in a relatively large group of patients with KLS. During the years 1982–97, we encountered 34 patients (26 males and eight females) with KLS. We were able to obtain the original polysomnographs from 28 males and four females. In 25 patients, data regarding their present state of health were obtained. Fourteen agreed to be present at a detailed interview and examination while 11 gave the information by phone. The mean age at onset was 15.8 ± 2.8 years and the mean diagnostic delay, 3.8 ± 4.2 years. The mean duration of a single hypersomnolent attack was 11.5 ± 6.6 days. The main abnormal findings extracted out of 35 polysomnographs obtained from 32 patients during and/or in‐between attacks included: decreased sleep efficiency, and frequent awakenings from sleep stage 2. All 25 patients reported present perfect health, with no evidence of behavioral or endocrine dysfunction. In adolescents with periodic hypersomnia, the diagnosis of KLS should be explored. Sleep recordings during a hypersomnolent period will often show frequent awakenings from sleep stage 2. The long‐term prognosis is excellent.
Spindle frequencies in sleep EEG show U‐shape within first four NREM sleep episodes
Authors: HIMANEN SARI‐LEENA , VIRKKALA JUSSI , HUHTALA HEINI , HASAN JOEL
Published: March 2003

It has been shown in previous studies on sleep electroencephalogram (EEG) that spindles are slower in the beginning of the night fastening towards the end of the night. Corresponding findings have been obtained by spectral analysis. The present study was based on our preliminary observation that slower spindles are found in the middle of the nonrapid eye movement (NREM) sleep episodes as compared with the beginning or the end of the episodes. Eight healthy female and six male subjects were studied. Sleep spindles were visually selected and spindle frequencies calculated for 11 analysis points in each NREM sleep episode. The median spindle frequencies formed a clear U‐shape within NREM sleep episodes with an initial decrease and final increase. The decrease was statistically significant within the first four NREM sleep episodes. It is possible that the spindle frequency pattern could be used to reveal variations in sleep depth within sleep stage 2. In animal studies the spindle frequency has been found to be associated to the duration of the hyperpolarization‐rebound sequences of the thalamocortical cells. If it is assumed that the same cellular mechanisms are responsible for spindle frequencies in humans then the study of variations in spindle frequency could be used to examine the NREM sleep process in humans.
A prospective study of fatal occupational accidents – relationship to sleeping difficulties and occupational factors
Authors: ÅKERSTEDT T. , FREDLUND P. , GILLBERG M. , JANSSON B.
Published: March 2003

Very little is known about the association between sleep and (fatal) occupational accidents. This study investigated this relationship using register data of self‐rated sleep difficulties, together with occupational and demographic characteristics. The variables were related to subsequent occupational fatal accidents. A national sample of 47 860 individuals was selected at regular intervals over a period of 20 years, and interviewed over the phone on issues related to work and health. The responses were linked to the cause of death register (suicides excluded) and the data set was subjected to a (multivariate) Cox regression survival analysis. One hundred and sixty six fatal occupational accidents occurred, and the significant predictors were: male vs. female: relative risk (RR)=2.30 with a 95% confidence interval (CI) of 1.56–3.38; difficulties in sleeping (past 2 weeks): RR=1.89 with CI=1.22–2.94; and non‐day work: RR=1.63 with CI=1.09–2.45. No significant effect was seen for age, socio‐economic group, hectic work, overtime (>50 h per week), or physically strenuous work. It was concluded that self‐reported disturbed sleep is a predictor of accidental death at work, in addition to non‐day work and male gender.
Affinity of detomidine, medetomidine and xylazine for alpha‐2 adrenergic receptor subtypes
Authors: Schwartz D.D. , Clark T.P.
Published: March 2003

α 2‐Adrenergic receptor agonists are widely used in veterinary medicine as sedative/hypnotic agents. Four pharmacological subtypes of the α2‐adrenergic receptor (A, B, C and D) have been identified based primarily on differences in affinity for several drugs. The purpose of this study was to examine the affinities of the sedative agents, xylazine, detomidine and medetomidine at the four α2‐adrenergic receptor subtypes. Saturation and inhibition binding curves were performed in membranes of tissues containing only one subtype of a2‐adrenergic receptor. The KD for the α2‐adrenergic receptor radioligand, [3H]‐MK‐912, in HT29 cells (α2A‐), neonatal rat lung (α2B‐), OK cells (α2C‐) and PC12 cells transfected with RG20 (α2D‐) were 0.38 ± 0.08 nm, 0.70 ± 0.5 nm, 0.07 ± 0.02 nm and 0.87 ± 0.03 nm, respectively. Detomidine and medetomidine had approximately a 100 fold higher affinity for all the α2‐adrenergic receptors compared to xylazine but neither agonist displayed selectivity for the α2‐adrenergic receptor subtypes. These data suggest that available sedative/hypnotic α2‐adrenergic receptor agonists can not discriminate between the four known α2‐adrenergic receptor subtypes.
Disposition and metabolism of the novel macrolide antibiotic CP‐163505 in cattle
Authors: Linhares M.C. , Harran L.F. , Strelevitz T.J. , Gauthier J.W. , Cole M.J. , Hassfurther R.L. , Risk J.E.
Published: March 2003

The plasma pharmacokinetics, lung tissue to plasma concentration ratios, and depletion profiles in edible tissue (liver, muscle, kidney, fat and injection site) for a single subcutaneous dose of a novel macrolide antibiotic, CP‐163505 (20‐[3‐dimethylaminopropyl(L‐alanyl)amino]‐20‐deoxo‐repromicin), were investigated in crossbred beef cattle. Mean peak plasma concentration of 2.5 ± 0.4 μg/mL, occurring at 0.5 h, was found for CP‐163505 following a 5 mg/kg dose (n = 5). The pharmacokinetic profile consisted of a distribution phase, followed by an extended terminal elimination phase (t1/2of 19 h). The disposition of CP‐163505 was characterized by distribution from the plasma into the tissue resulting in lung to plasma ratios of 103 and 87 at 72 h following a single 5 or 10 mg/kg dose, respectively. The depletion of CP‐163505 from edible tissues was determined following administration of tritiated CP‐163505 at a dose of 10 mg/kg. On day 42, the liver contained the highest mean concentration of total tritium residues, 5.9 ± 3.4 μg/g. CP‐163505 was determined to be a significant component of the total residues in liver with 72% on day 3 and 50% on day 42. Three metabolites of CP‐163505 were identified by liquid chromatography with mass spectrometry (LC/MS/MS) in liver samples: loss of alanine, formation of an hydroxyl derivative, and sulfate addition to the lactone ring.
Water medication of a swine herd with amoxycillin
Authors: AGERSØ H. , FRIIS C. , HAUGEGAARD J.
Published: March 2003

A swine herd, consisting of 201 swine, was treated with amoxycillin. Amoxycillin was administered in the water system for 5 days, at a mean dose of 23 mg/kg body weight per day. Twice a day the water consumption was monitored, and blood samples collected from 10 randomly selected pigs. The plasma concentration of amoxycillin was measured by use of high performance liquid chromatography (HPLC). Three days after initiating amoxycillin treatment, the plasma concentration reached a constant level, at which it varied between a maximum of 1.3 μg/mL and a minimum of 0.5 μg/mL. The plasma concentration was compared with a predicted curve based on pharmacokinetic variables obtained previously. The plasma concentrations were at the same level as the simulated ones. The minimum inhibitory concentration (MIC) values of the common respiratory pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida are about 0.1 μg/mL. In pigs the distribution between bronchial mucosa and plasma (AUCmucosa/AUCplasma) is 0.3, which indicates a therapeutic plasma concentration of 0.3 μg/mL. Data from the present study indicates that water medication with amoxycillin is effective as follow‐up treatment.
Pharmacokinetics and dosage regimen of 2‐pyridine aldoxime in Bubalus bubalis intoxicated with fenitrothion
Authors: Srivastava A. K. , Malik J. K.
Published: March 2003

In the present study, the pharmacokinetics of 2‐pyridine aldoxime (2‐PAM, 30 mg/kg, i.v.) alone and in conjunction with atropine (0.3 mg/kg; 1/4 i.v., 3/4 i.m.) was investigated in 10 Bubalus bubalis intoxicated with a single oral lethal dose of fenitrothion (435 mg/kg). Based on the kinetic parameters, an appropriate dosage regimen of 2‐PAM in B. bubalis was calculated. There was no significant difference between plasma levels and pharmacokinetic parameters of 2‐PAM in the two groups of animals, given 2‐PAM alone and in conjunction with atropine. The peak plasma concentration of 2‐PAM at 1 min was in the range of 189.5–196.6 μg/mL which declined to 9.22–9.98 μg/mL at 4 h. The values of elimination half‐life, Vd(area) and total body clearance were 2.41–2.67 h, 0.77–0.95 L/kg and 227.5–245.7 mL/kg/h, respectively. The binding capacity of 2‐PAM to plasma proteins of fenitrothion‐intoxicated buffalo calves and dissociation rate constant of protein drug complex were 0.015 × 10−6 mol/g and 2.367 × 10−6 mol, respectively. Approximately 63% of 2‐PAM was bound with plasma proteins. In the treatment of organophosphate insecticide (OPI) toxicity in B. bubalis, an appropriate i.v. dosage regimen of 2‐PAM in conjunction with atropine would be 18 mg/kg followed by 15 mg/kg at 4 h interval.
Study of Ligmed‐A, an antidiarrheal drug based on lignin, on rat small intestine enzyme activity and morphometry
Authors: Mitjans M. , García L. , Marrero E. , Vinardell M. P.
Published: March 2003

This study aimed to determine the potential toxic effect of 4‐day oral treatment with a lignin‐based formulation on the enzymatic activity and morphology of the small intestine of rat. Ligmed‐A is collected from sugarcane and is used to treat diarrhea in weaning pigs. The compound is about 90% lignin, an insoluble polyphenolic constituent of plants and a component of dietary fiber. The duodenal, jejunal and ileal mucosa of control rats and those receiving 2 g/kg Ligmed‐A showed similar protein contents of about 100 mg/g. The sucrase and alkaline phosphatase activities of the three intestinal segments were unaltered after administration of the compound. Nonhistological alterations were observed after treatment. Our results, together with those of previous studies which found no toxicological effects, indicate that Ligmed‐A could provide a potent antidiarrheal treatment in the veterinary area. However, further studies are required to examine its use in humans.
Acetaminophen UDP‐glucuronosyltransferase in ferrets: species and gender differences, and sequence analysis of ferret UGT1A6
Authors: Court M. H.
Published: March 2003

The principal objective of this study was to determine whether ferrets glucuronidate acetaminophen more slowly compared with other species, and if so investigate the molecular basis for the difference. Acetaminophen‐UDP‐glucuronosyltransferase (UGT) activities were measured using hepatic microsomes from eight ferrets, four humans, four cats, four dogs, rat, mouse, cow, horse, monkey, pig and rabbit. Gender differences between male and female ferret livers were explored using enzyme kinetic analysis. Immunoblotting of microsomal proteins was also performed using UGT‐specific antibodies. Finally, the exon 1 region of UGT1A6, a major acetaminophen‐UGT, was sequenced. Glucuronidation of acetaminophen was relatively slow in ferret livers compared with livers from all other species except cat. Gender differences were also apparent, with intrinsic clearance (Vmax/Km) values significantly higher in male compared with female ferret livers. Furthermore, Vmax values correlated with densitometric measurements of two protein bands identified with a UGT1A subfamily‐specific antibody. No deleterious mutations were identified in the exon 1 or flanking regions of the ferret UGT1A6 gene. In conclusion, like cats, ferret livers glucuronidate acetaminophen relatively slowly. However, unlike cats, in which UGT1A6 is encoded by a pseudogene and dysfunctional, there are no defects in the ferret UGT1A6 gene which could account for the low activity.
Isoxsuprine hydrochloride in the horse: a review
Authors: ERKERT R. S. , MACALLISTER C. G.
Published: March 2003

Isoxsuprine hydrochloride has been suggested for use in horses for treatment of navicular syndrome and laminitis. The drug has been shown to be a β‐adrenoreceptor antagonist with β‐adrenoreceptor agonistic properties, with both characteristics contributing to vasodilation and uterine relaxation. In addition, the drug is capable of decreasing blood viscosity and platelet aggregation. Studies have shown i.v. isoxsuprine to have a plasma half‐life of <3 h with a large apparent volume of distribution. Cardiovascular effects resolve rapidly following i.v. administration, but are absent with oral dosing. Oral bioavailability is 2.2% with a high first pass effect. Isoxsuprine has an apparent affinity for melanin that may contribute to extended renal excretion. Clinical trials appear to support the use of isoxsuprine for treatment of navicular disease. However, poor bioavailability, lack of cardiovascular effects following oral administration, superficial support in clinical trials, and new evidence regarding the pathogenesis of navicular syndrome indicate that the use of isoxsuprine for treatment of navicular syndrome or laminitis is questionable at best.
Lack of daily rhythms major modifications despite continuous infusion of melatonin in the rat
Authors: Simon, N. , Vidal, J. , Mouchet, J. , Bruguerolle B.
Published: March 2003

The present study was conducted to evaluate the effect of melatonin on the daily rhythms of temperature, heart rate and locomotor activity in rats that received subcutaneously a continuous infusion of two different doses e.g. 1 and 5 mg/kg per day for seven days. Our results indicate that melatonin does not induce a loss of the daily rhythmicity of temperature, heart rate and locomotor activity. Whatever the dose, melatonin slightly modifies the main parameters of these rhythms e.g. a decrease of the amplitude of the daily rhythms of temperature and heart rate and an increase of the mesor of temperature. Taking into account these results obtained after constant rate delivery in normal rats, we plan now to investigate the effects of melatnonin on our experimental model of Parkinson's disease (double bilateral intrastriatal 6‐hydroxydopamine injection).
Role of the specific T‐cell response for clearance and control of hepatitis C virus
Authors: Pape G. R. , Gerlach T. J. , Diepolder H. M. , Grüner N. , Jung M.‐C. , Santantonio T.
Published: March 2003

T cells are believed to be the main players in antiviral defence. To investigate the role of the specific CD4+ T cell response for clearance and control of the hepatitis C virus we studied patients with acute hepatitis C (AHC) during the phase of spontaneous viral clearance and during follow up after elimination of the virus and resolution of disease. Symptomatic AHC has a self‐limited course in 50% of patients, whereas the other half show virus persistence and develop chronic course of disease. Patients who were able to mount a vigorous, polyclonal, multispecific, TH1 lymphokine dominated CD4+ T‐cell response showed viral clearance and a self‐limited course of disease. In contrast, absence of this T‐cell response in patients with AHC invariably led to viral persistence and chronic hepatitis. The characteristics of the T‐cell response were as follows: it was mainly directed against nonstructural proteins of the virus, it was multispecific and demonstrated immunodominant epitopes, and the majority of T‐cell clones established from our patients responded to a single peptide (NS3 aminoacid 1248–1261) within the helicase region of HCV. Presentation of the peptide was HLA DR specific, the peptide showed promiscous binding, and it had high binding affinity to 10 of the most common 13 HLA DR alleles, thus patients with diverse HLA DR backgrounds could mount an immune response. Furthermore, the epitope was conserved in 100% of 33 HCV strains published in databases. This strong initial CD4+ T‐cell response is not sufficient for a definitive recovery from AHC, it has to be maintained to control the hepatitis C virus. Loss of the response after initial resolution of disease is followed by relapse. Even 20 years after an episode of self‐limited AHC with elimination of HCV, we have observed a significant virus‐specific CD4+ T‐cell response. Our data indicate the decisive role of the virus‐specific CD4+ T‐cell response for clearance and control of HCV, and contribute to our understanding of immune mechanisms by which the host defends the HCV virus. This is a prerequisite for the development of new strategies to efficiently defend the virus by manipulating or modulating the immune response.
Correlation between hepatitis C virus prevalence and hepatocellular carcinoma mortality in Europe
Authors: Deuffic S. , Poynard T. , Valleron A. ‐J.
Published: March 2003

In Europe, as worldwide, hepatocellular carcinoma (HCC) death rates are highly variable. Recent studies have reported that hepatitis C virus (HCV) infection may be responsible for the increased mortality from HCC in the UK and in France. We investigate here the potential relationship between HCC mortality and HCV prevalence in Europe. Population and mortality data of HCC were obtained for 22 European countries from the World Health Organization (WHO) databank. Age‐standardized death rates were computed. The HCV prevalence among blood donors and the WHO estimate of HCV prevalence were used as two indicators of prevalence in the general population, when data were available. Spearman rank analysis was conducted between HCC mortality and HCV prevalence. For men, age‐standardized death rates per 100 000 varied from 0.61 (Greece) to 12.19 (Hungary). HCC mortality among men was positively correlated with HCV prevalence among blood donors and with the WHO estimate: rank correlation coefficients were, respectively, 0.76 (P = 0.02) and 0.72 (P = 0.03). This study showed that the reported differences of HCC mortality in Europe correlate with HCV prevalence.