bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Behavioural Effects of Corticosterone Lack Specificity but Show Marked Context‐Dependency
Authors: Haller Jozsef , Albert Ibolya , Makara Gabor B.
Published: November 2003

Rats were injected intraperitoneally with corticosterone (1 mg/kg). Ten min later they were submitted to dyadic encounters for 15 min. Rats naive to aggressive encounters responded to the corticosterone treatment by a reduction in resting times and an increase in exploration directed towards the novel environment. Resident rats acquainted with aggressive encounters responded to the treatment by a reduction of resting and an increase in threat behaviours. In resident rats acquainted with aggressive encounters and reared previously with a female an increase in attack frequency was noticed. It is concluded that an acute increase in blood corticosterone results in a stimulation of behaviour during social challenge, however, the specific effect is highly context dependent. These data confirm sporadic reports that noticed a behavioural stimulatory effect of acute corticosterone treatments. However, as far as a social challenge situation is concerned, the effect of corticosterone seems to be rather context then behaviour specific. Since corticosterone is known rather to change neuronal excitability than to activate neurons by itself, one can hypothesize that the context dependency of the effect is determined by the different configuration of activated centres in different situations. Attack may be stimulated by corticosterone only when centres involved in attack are already activated, that is, when a high frequency of attack is already present.
Kinetics of Radiolabeled Adrenocorticotropin Hormone in Infant and Weanling Rats
Authors: Vázquez Delia M. , Morano María I. , Larry Taylor  , Akil Huda
Published: November 2003

Unlike the adult animal, the developing rat has a diminished ability to activate and inhibit the hypothalamic pituitary adrenal axis. In general, a gradual ACTH and corticosterone response to stressors appear after postnatal day 10 and is well established to adult level by weaning age. Although at this age the peak ACTH level is comparable to that of the adult, ACTH levels remain elevated for a longer period of time. The purpose of this study was to investigate the possibility that ACTH metabolism can, in part, explain this prolonged ACTH elevation after a challenge. The plasma half life of disappearance (t1/2), the apparent volume of distribution and metabolic clearance rate (MCR) were determined after injection of a tracer dose of 3‐I125‐Iodotyrosyl23 ACTH1–39 in rats at 14 and 25 days of age. An adult animal group (65 days old) was used for comparison. The t1/2 for ACTH decreases with age (14 day old=7.47±0.9 min; 25 day old=6.48±0.4 min; adult=4.46±0.2 min) while the volume of distribution remains constant. The MCR is also decreased in the young animals (14 day old=1.5±0.19 min; 25 day old=1.6±0.18 min; adult=3.0±0.56 min). For the first time, it is established that the young animals require longer to clear ACTH from an equivalent volume of blood when compared to the adult. Thus, the kinetic properties of ACTH are different in the developing animal and this partly explains the prolonged ACTH elevation observed after stress challenges.
The Interactive Language of the Hypothalamus for the Gonadotropin Releasing Hormone (GNRH) System
Authors: Kalra Satya P. , Horvath Tamas , Naftolin Frederick , Xu Bin , Pu Shuye , Kalra Pushpa S.
Published: November 2003

The enormous diversity in neurochemical signals employed within the network of afferents to GnRH neurons is well‐documented. An examination of novel and accumulating knowledge on the operation of these messengers indicates the presence of an interactive language governing GnRH secretion. The basic operational structures identified to date to affirm this interactive form of communication summarized in this review are the following: (i) the demonstration of interconnections within various components of the afferent network; (ii) coexistence and possible co‐release of excitatory and inhibitory neurotransmitters/ neuromodulators; (iii) co‐action of various messengers at synaptic targets, and (4) modulation by gonadal steroids of the synthesis and release of signals and their receptors, and induction of synaptic plasticity for the timely relay of signals for GnRH secretion. Unraveling the molecular sequelae that promote this interactive communication to elicit periodic GnRH secretion is now a new challenge.
Regulation of Pituitary Corticotropin Releasing Hormone (CRH) Receptor mRNA and CRH Binding During Adrenalectomy: Role of Glucocorticoids and Hypothalamic Factors
Authors: Rabadan‐Diehl Cristina , Makara Gabor , Kiss‡ Alexander , Zelena Dora , Aguilera Greti
Published: November 2003

The role of glucocorticoids and hypothalamic factors on CRH receptor expression in the pituitary were studied by analysis of the effects of adrenalectomy and suppression of CRH and VP secretion by hypothalamic lesions in the rat. Consistent with previous in situ hybridization studies, Northern blots showed that pituitary CRH receptor mRNA decreased only transiently after adrenalectomy, falling to 51% of the control levels after 18 h, and returning to control values after 6 days (112%). The early decrease was prevented by dexamethasone injection, 100 &mgr;g, s.c. The role of increased levels of CRH and VP in the pituitary portal circulation on the transient decrease in CRH receptor mRNA levels after adrenalectomy were studied by in situ hybridization in rats subjected to PVN lesions or median eminence deafferentation by hypothalamic anterolateral cuts (ALC). PVN lesion (12 days) or ALC (8 days) resulted in undetectable irCRH and VP in the external zone of the median eminence and had no effect on basal levels of pituitary POMC mRNA, CRH binding and CRH receptor mRNA. In sham lesioned rats, adrenalectomy for 18 h or 4 days caused the expected increases in pituitary POMC hnRNA and mRNA, and decreases in CRH binding. CRH‐R mRNA levels decreased by about 50% after 18 h adrenalectomy but returned to basal by 4 days. PVN lesion or ALC fully prevented the fall in CRH binding after 18 h or 4 days adrenalectomy and the increase in POMC mRNA after 4 days adrenalectomy, whereas only attenuated the decrease in CRH receptor mRNA and increase in POMC mRNA levels after 18 h adrenalectomy. Administration of a CRH antagonist did not affect CRH receptor mRNA and POMC hnRNA and mRNA indicating that residual CRH in the median eminence after hypothalamic surgery is not responsible for the effect of adrenalectomy. These studies confirm previous in situ hybridization studies showing that adrenalectomy causes transient decreases in pituitary CRH receptor mRNA levels. The data indicate that while increases in hypothalamic CRH secretion following glucocorticoid withdrawal mediate pituitary CRH receptor binding loss and the increase in POMC expression after long‐term adrenalectomy, CRH only partially accounts for the early changes in CRH receptor mRNA and POMC mRNA.
Castration Decreases Single Cell Levels of mRNA Encoding Glutamic Acid Decarboxylase in the Diagonal Band of Broca and the Sexually Dimorphic Nucleus of the Preoptic Area
Authors: Sagrillo Cathleen A. , Selmanoff Michael
Published: November 2003

Using quantitative in situ hybridization histochemistry (ISHH), we determined the effect of castration on single cell levels of glutamic acid decarboxylase (GAD) mRNA in discrete hypothalamic regions of the male rat brain associated with the control of gonadotropin secretion. A 48‐base oligodeoxynucleotide probe was used to detect with equal affinity the two isoforms of GAD message, GAD65 and GAD67. GAD message also was quantitated in a number of selected areas of the brain to contrast GAD gene expression amongst several populations of GABAergic neurons. Comparison of 11 brain regions demonstrated a 9.3‐fold range in the quantity of single cell GAD mRNA with levels being highest in the amygdala and the diagonal band of Broca, moderate in the piriform cortex, caudate nucleus, substantia innominata, globus pallidus, cingulate cortex and medial septal nucleus, and lowest in the lateral septal nucleus and the medial preoptic nucleus (MPN). Castration markedly reduced single cell GAD mRNA levels in the DBB and the MPN, two discrete hypothalamic structures known to contain dendritic fields, cell bodies, and axons of GnRH neurons projecting to the median eminence. A striking finding was a dense core of steroid‐sensitive GABAergic neurons within the MPN comprising the sexually dimorphic nucleus of the preoptic area (SDN‐POA). Similar to the MPN as a whole, the amount of GAD mRNA expressed by cells in the SDN‐POA of sham operated control rats was greater than in castrated animals. GAD mRNA levels were inversely related to serum LH titers, suggesting a role for these neurons in the mechanism controlling gonadal steroid negative feedback on LH secretion. This report provides the basis for future work to determine if GAD65, GAD67 or whether both isoforms are affected by gonadal steroid input.
Response of Substance P‐Immunoreactive Nerve Fibres in the Anterior Pituitary to Plasma Oestrogen Levels in the Rat
Authors: Ma Dan , Zhao Chao , Mayhew T. M. , Ju Gong
Published: November 2003

The mammalian anterior pituitary has recently been shown to be innervated by substantial amounts of peptidergic nerve fibres. It has also been found that adrenalectomy increases the amount of calcitonin gene‐related peptide‐like immunoreactive nerve fibres in the anterior pituitary of the rat, and that stimulation of the nerve fibres in vitro can enhance release of ACTH. In the present study, the density of substance P‐like immunoreactive nerve fibres in the anterior pituitary of the rat were examined in relation to variations in plasma oestrogen status. The amount of substance P‐like immunoreactive nerve fibres increased significantly (P<0.001) after ovariectomy, and decreased significantly (P<0.01) under oestrogen replacement, in a dose‐dependent manner. The results suggest the possibility of the direct neural involvement of oestrogen secretion in anterior pituitary regulation, which further substantiates the hypothesis of neural‐humoral dual regulation of the mammalian anterior pituitary.
Rapid Changes of Heteronuclear RNA for Arginine Vasopressin but not for Corticotropin Releasing Hormone in Response to Acute Corticosterone Administration
Authors: Ma Xin‐Ming , Levy Andrew , Lightman Stafford L.
Published: November 2003

Corticotropin‐releasing hormone and arginine vasopressin gene transcription were studied in the parvocellular cells of the hypothalamic paraventricular nucleus in response to both adrenalectomy and the injection of corticosterone. Following 6 days ADX, there was an increase in AVP mRNA, AVP hnRNA and CRH mRNA but not CRH hnRNA. After injection of corticosterone in ADX rats there was an extremely rapid reduction in AVP hnRNA which fell markedly within 15min. AVP mRNA, however, remained raised throughout the 4 h. CRH hnRNA fell at 2 and 4 h, while CRH mRNA was only significantly reduced at the 4 h time point. Data demonstrate markedly different kinetics for the glucocorticoid regulation of the AVP and CRH genes in the hypothalamus.
Preproenkephalin mRNA is Regulated by an Interaction Between Steroid Hormones and Nociceptive Stimulation
Authors: Holtzman David A. , Brooks Phillip J. , Pfaff Donald W. , Schwartz‐Giblin Susan
Published: November 2003

The expression of preproenkephalin (PPE) mRNA has previously been shown to be regulated by steroid hormones in the ventromedial nucleus of the hypothalamus (VMH) and to be regulated by noxious stimuli in the dorsal horn of the spinal cord (DH). The present in situ hybridization study in ovariectomized rats showed that PPE mRNA expression in both the VMH and the lumbar DH, responds to the interaction between a noxious peripheral stimulus and ovarian steroid hormones. In the VMH, either estradiol or estradiol+progesterone increased the mean PPE mRNA content per cell by 100% compared with vehicle‐treated rats. Unilateral hindpaw injection of 5% formalin, as compared to saline, significantly increased mean PPE mRNA content per VMH cell in rats treated with vehicle or estradiol but not those treated with estradiol+progesterone. Regression analysis for mean PPE mRNA content per VMH cell as a function of intensity of hindpaw inflammation showed a significant positive correlation coefficient after vehicle and estradiol treatment (P<0.02) but a strong trend towards a negative correlation coefficient after estradiol+progesterone treatment (P<0.06). ANOVA for homogeneity of regression coefficients showed a significant difference across hormone groups (P<0.01).
Dehydroepiandrosterone 7α‐ and 7β‐Hydroxylation in Mouse Brain Microsomes. Effects of Cytochrome P450 Inhibitors and Structure‐Specific Inhibition by Steroid Hormones
Authors: Doostzadeh J. , Cotillon A. C. , Morfin R.
Published: November 2003

Presently, several works question the effects of dehydroepiandrosterone (DHEA) reported in vivo and designate its 7‐hydroxylated metabolites as native antiglucocorticoids and potent mediators in the triggering of immune response. Among mouse tissues and organs, and second to liver, the largest production of 7α‐and 7β‐hydroxylated derivatives of DHEA takes place in brain microsomes. To contribute to identification of cytochromes P450 (CYPs) responsible for 7α‐ and 7β‐hydroxy‐DHEA production, effects of CYP inhibitors and of several steroid hormones on DHEA 7‐hydroxylation were examined. Using mouse brain microsomes as a source of enzyme, we report now that strong and smaller inhibitions of DHEA 7α‐hydroxylation were obtained with ketoconazole and α‐naphthoflavone, respectively, and that neither changed DHEA 7β‐hydroxylation. Metyrapone and antipyrine also inhibited 7α‐hydroxylation, but by contrast, significantly increased 7β‐hydroxylation of DHEA. This indicated that at least, two different CYPs were responsible for 7α‐ and 7β‐hydroxylation of DHEA. Steroids sharing a 3β‐hydroxylated structure with DHEA, namely pregnenolone, 5‐androstene‐3β,17β‐diol and 3β‐hydroxy‐5α‐androstan‐17‐one, were strong inhibitors of DHEA 7α‐hydroxylation (non‐competitive inhibition with pregnenolone, Ki=2.0±0.3 μM). In contrast, 7β‐hydroxylation yields were not decreased by the 3β‐hydroxysteroids tested. Moderate inhibition of 7α‐ and 7β‐hydroxylation was obtained with 3‐oxosteroids, namely testosterone, progesterone, corticosterone and 4‐androsten‐3,17‐dione. Taken together, these data indicate specific inhibition patterns of DHEA 7α‐ and 7β‐hydroxylation by CYP inhibitors and steroid hormones in mouse brain microsomes and may be used as criteria necessary for identification of the responsible CYP species.
Melatonin Inhibits GnRH‐Induced Increase of cFOS Immunoreactivity in Neonatal Rat Pituitary
Authors: Alena Sumova  , Vanecek Jiri
Published: November 2003

In neonatal rat gonadotrophs, melatonin inhibits several GnRH‐induced effects: stimulation of LH release as well as the increase of several second messengers as cAMP, diacylglycerol and [ Ca2+]i . Recently, GnRH has been shown to induce expression of immediate early genes of fos and jun family in adult rat gonadotrophs. The purpose of this study was to determine, whether melatonin inhibits the GnRH‐induced induction of cFos in neonatal rat pituitary cells.
Relationship between alignment conditions of teeth in anterior segments and incisal wear
Authors: BERGE M. , JOHANNESSEN G. , SILNESS J.
Published: November 2003

This report describes the alignment condition and incisal wear of the anterior teeth in individuals 16–19 years of age. Tooth alignment and incisal wear were assessed on casts in accordance with two index systems NONAT (non‐aligned tooth) and IwI (incisal wear index). Tests of the methods showed that the reproducibility of the assessments of tooth alignment and incisal wear were satisfactory. The results of the study of tooth irregularity demonstrated that the prevalence of non‐alignment of one or more of the anterior teeth were much the same (∼50%) for the maxillary and mandibular jaws. The highest frequency was found for the maxillary lateral incisors and the mandibular central incisors (∼45%). A relationship between the alignment conditions and incisal wear of the anterior teeth was established. It appeared that non‐alignment of one or more teeth in one or both jaws was associated with less severe incisal wear of the anterior teeth. This was most pronounced for non‐aligned maxillary central incisors and non‐aligned mandibular central incisors.
Biostereometric quantification of clinical denture tooth wear
Authors: ADAMS L.P. , JOOSTE C.H. , THOMAS C.J. , HARRIS A.M.P.
Published: November 2003

In this study the wear of mandibular acrylic resin teeth opposed by porcelain maxillary teeth arranged in a lingualized occlusal scheme over a period of 3 years was measured. Six edentulous subjects received complete dentures as above and with three baseline markers of amalgam. At yearly intervals casts were made of the mandibular occlusal surfaces, including markers, and plotted by stereophotogrammetry. Volumetric loss of material was quantifiable. Ranges of 0·62–3·33 mm3/mm2 on the left side and 0·71–1·64 mm3/mm2 on the right were recorded. Friedman two‐way ANOVA test indicated significant wear on teeth 35, 36, 45 and 46 but not on 34 and 44. A one‐sided chewer displayed greater wear on the contralateral side, a finding difficult to explain.
Nurses and neuroleptic medication: applying theory to a working relationship with clients and their families
Authors: Usher K. J. , Arthur D.
Published: November 2003

This paper presents a model for the nursing management of the effects of neuroleptic or antipsychotic medication. The model addresses the contemporary issues facing nurses, their clients and families, while at the same time is congruent with the continua of effects of these medications. For many, nonadherence is directly related to undesired side effects, while for others the reasons may be multidimensional. The proposed model addresses the notion of advocacy and empowerment in the light of interventions that relate to the undesired‐desired effects continuum. Underpinning this is the notion of the phases of the nurse‐client relationship, which were advocated by Peplau (1952) and have since offered a framework for nursing intervention. While developing the phases of this relationship, nurses can help the client and family by assuming various roles that can enhance the relationship. It is suggested that each of these roles has an element of advocacy and an element of empowerment. It is part of the nurses' professional responsibility to help the client and their family to deal with the issues surrounding medication nonadherence.
Generating ideas for teaching mental health nursing
Authors: McAllister M. , Ryan M.
Published: November 2003

University teachers who prepare mental health nurses require a variety of teaching techniques to encourage students to engage with the subject matter and to prepare for unknown future problems and dilemmas that they must resolve. Mental health nursing requires the development of specific discipline knowledge, intellectual skills, such as the ability to think laterally and make ethical decisions, and personal attributes, such as maturity and tolerance, as well as practical experience in collaborative care. This article offers a number of strategies that teachers may use in their classes to promote the development of these mental health nursing skills. Other teachers might use these examples to trigger the development of their own repertoire of teaching skills for beginning mental health nurses.
Evaluation of a low‐threshold clinic for opiate‐dependent drug users
Authors: Ryrie I. W. , Dickson J. , Robbins C. , Maclean K. , Climpson C.
Published: November 2003

This study reports on the development and outcome of a Low Threshold Clinic (LTC) for opiate‐dependent drug users. The service originated as a nursing initiative within an inner city Drug Dependency Centre (DDC) and its rationale and treatment approach are explored in relation to the literature and local circumstances. Client baseline and outcome data were systematically gathered to assess service uptake and service efficacy in terms of client outcome. Data are presented for the first two years of operation during which a total of 59 clients entered the LTC. The sociodemographic characteristics and patterns of drug use among this group suggest the service was successful in targeting clients who previously failed to enter traditional treatment programmes despite initial referral to the DDC. Outcome data indicate a tendency for clients to inject less frequently, engage in less criminal activity and, by 12 months, to reduce their dose of prescribed methadone whilst attending the LTC. Tentative conclusions are drawn concerning the value of this service for ‘hard‐to‐reach’ drug users and those who may be at a precontemplation stage of change. Recommendations are made for a more comprehensive evaluative study that involves comparison with other treatment approaches.
A systematic review of the psychiatric/mental health nursing research literature 1982–1992
Authors: Yonge O. , Austin W. , Zhou Qiuping P. , Wacko M. , Wilson S. , Zaleski J.
Published: November 2003

The purpose of this study was to assess the quality of quantitative psychiatric/mental health nursing research articles published in English between 1982 and 1992, worldwide. Criteria for selection of articles included nurse authorship or co‐authorship, use of a quantitative design and pertinence to an aspect of the nursing process with psychiatric/mental health patients. One hundred and ninety‐four articles met these criteria. The quality of each article was assessed by two nurse experts using Duffy's Research Appraisal Checklist (RAC). Forty‐six point nine per cent of the articles were rated as superior, 50% as average and 3.1% as below average. Other findings identified journals that published research articles, countries in which research was completed, applicability of funding and qualifications of the authors. The major implications of this study are that nurses can be directed to superior articles; more publication of research by nurse authors is warranted, research is being completed with little financial support, highly rated research publications tend to get funding and editorial policies affect the quality of publication.
Sexual abuse comfort scale: a scale to measure nurses' comfort to respond to sexual abuse in psychiatric populations
Authors: McCay E. , Gallop R. , Austin W. , Bayer M. , Peternelj‐Taylor C.
Published: November 2003

The purpose of the present study was to further contribute to the psychometric evaluation of the Sexual Abuse Comfort Scale (SACS) in order to provide a standardized measure that would assess the impact of educational programmes on nurses' comfort to intervene with psychiatric clients regarding sexual abuse. This study was part of a larger multisite study conducted in four Canadian provinces, designed to assess the attitudes, beliefs, competencies and educational needs of psychiatric nurses who may work with clients who have been sexually abused. As part of the larger study, a self‐administered survey was sent to 3532 psychiatric nurses employed in Alberta, Saskatchewan, Ontario and Nova Scotia. The SACS, the Sexual Attitudes Scale (SAS), the Questionnaire Measure of Emotional Empathy (QMEE) and the Marlowe‐Crowne Social Desirability Scale (M‐CDS) were included in the survey. The SACS was submitted for item analysis, factor analysis, hypothesis testing regarding construct validity and assessment of concurrent validity. Item analysis of the SACS resulted in a 30‐item scale with a coefficient of 0.91, indicating an excellent level of reliability. Empirical evidence indicates that the SACS is a reliable and valid instrument that may be used for the effective evaluation of intervention programmes directed towards increasing clinical knowledge and competence related to sexual abuse.
Assessing and managing risk of violence in the mentally disordered
Authors: Allen J.
Published: November 2003

This review paper explored the concepts of risk assessment and management in relation to ‘serious’ violence by individuals with mental disorder. The paper highlighted the political context in which concern over serious violence by those with mental disorder is increasing. Government guidance on risk assessment was considered and identified as having an actuarial bias. Correlational studies, which provide actuarial indicators of risk, were explored and a picture was developed that demonstrated the difficulty of determining risk of violence to others simply on the basis of psychiatric symptomatology. The literature led to a conclusion that risk assessment for violence is an inexact science, and that actuarial indicators need to be supported by structured thorough clinical investigation. Legal concerns around the assessment and management of risk were also explored. The Health and Safety Executive model for risk management was explored in relation to the findings of the risk‐assessment literature and the recommendations of reports into serious violent incidents. The model was shown to have potential utility in providing a legally sound framework for the assessment and management of risk of violence in mental disorder.
Vertical inversion of the visual field and REM sleep mentation
Authors: De Koninck Joseph , PRÉVOST FRANÇOIS , LORTIE‐LUSSIER MONIQUE
Published: November 2003

The effects of the vertical inversion of the visual field on REM sleep mental activity were examined to explore the potential involvement of this activity in information processing. In a first experiment, four male subjects slept in the laboratory for two sessions of 6 consecutive nights: 2 adaptation nights, 2 nights of polysomnography and 2 nights of dream collection. During the days preceding Nights 3, 4, 5, 6 of each session, the subjects wore glasses which, during the second session, completely inverted (rotation of 180°) their visual field. In a second experiment with four other male subjects, the order of conditions was reversed and the experimental condition (visual inversion) was introduced twice. The data of the two experiments were combined. Overall, following visual inversion, there were significant increases in the proportion of dreams containing motor and visual difficulties (P<0.005), misfortunes (P<0.05) and dreamer confusion (P<0.05) and a decrease in dreamer participation (P<0.05). Only 4 of the 8 subjects experienced incorporations of the inverted visual field into their dreams and they tended to perform better on two of three tests of adaptation to the visual inversion. The observed changes in dreams are consistent with the notion of continuity between waking and dreaming since they appear to reflect the waking preoccupation and psychological state associated with visual inversion.
Effect of ambient temperature on arterial pressure variability during sleep in the rat
Authors: SEI HIROYOSHI , MORITA YUSUKE
Published: November 2003

Changes in mean arterial pressure (MAP) and heart rate (HR) during sleep were recorded at three ambient temperatures (Ta: 16, 22 and 28°C). MAP and HR during sleep increased with lowering of Ta. The increase in MAP during the transition from NREM to REM sleep was decreased by lowering the Ta. At 28°C, the average HR increased in going from NREM to REM sleep, while, at 16°C, it decreased. The coefficient of variation (CV%) of the MAP during REM sleep decreased as the Ta was lowered, while that seen during NREM sleep was unchanged. This study suggests that Ta has a greater effect than sleep stage on the MAP and HR, and that MAP variability during REM sleep is greater at higher Ta.
Muscle artifacts in the sleep EEG: Automated detection and effect on all‐night EEG power spectra
Authors: BRUNNER DANIEL , VASKO RAYMOND , DETKA CHRISTOPHER , MONAHAN JAMES , REYNOLDS III CHARLES , KUPFER DAVID
Published: November 2003

Owing to the use of scalp electrodes in human sleep recordings, cortical EEG signals are inevitably intermingled with the electrical activity of the muscle tissue on the skull. Muscle artifacts are characterized by surges in high frequency activity and are readily identified because of their outlying high values relative to the local background activity. To detect bursts of myogenic activity a simple algorithm is introduced that compares high frequency activity (26.25–32.0 Hz) in each 4‐s epoch with the activity level in a local 3‐min window. A 4‐s value was considered artifactual if it exceeded the local background activity by a certain factor. Sensitivity and specificity of the artifact detection algorithm were empirically adjusted by applying different factors as artifact thresholds. In an analysis of sleep EEG signals recorded from 25 healthy young adults 2.3% (SEM: 0.16) of all 4‐s epochs during sleep were identified as artifacts when a threshold factor of four was applied. Contamination of the EEG by muscle activity was more frequent towards the end of non‐REM sleep episodes when EEG slow wave activity declined. Within and across REM sleep episodes muscle artifacts were evenly distributed. When the EEG signal was cleared of muscle artifacts, the all‐night EEG power spectrum showed significant reductions in power density for all frequencies from 0.25–32.0 Hz. Between 15 and 32 Hz, muscle artifacts made up a substantial part (20–70%) of all‐night EEG power density. It is concluded that elimination of short‐lasting muscle artifacts reduces the confound between cortical and myogenic activity and is important in interpreting quantitative EEG data. Quantitative approaches in defining and detecting transient events in the EEG signal may help to determine which EEG phenomena constitute clinically significant arousals.
A tumor necrosis factor (TNF) receptor fragment attenuates TNF‐α‐ and muramyl dipeptide‐induced sleep and fever in rabbits
Authors: TAKAHASHI SATOSHI , KAPÁS LEVENTE , KRUEGER JAMES
Published: November 2003

It is hypothesized that tumour necrosis factor (TNF) is an endogenous substance involved in sleep responses occurring during bacterial infection. If this hypothesis is correct, then blocking endogenous TNF, using a TNF inhibitor, should attenuate the bacterial cell wall‐derived, muramyl dipeptide (MDP)‐induced sleep. To test this hypothesis, the effects of intracerebroventricular (i.c.v.) injection of a TNF inhibitor, a biologically active fragment of the soluble TNF 55 kDa receptor (TNFRF), on TNF‐α‐ and MDP‐induced sleep were determined in rabbits. I.c.v. injection of 250 ng human recombinant TNF‐α‐ or 150 pmol MDP increased non‐rapid‐eye‐movement sleep (NREMS), decreased rapid‐eye‐movement sleep (REMS), enhanced electroencephalogram slow‐wave activity (SWA) during NREMS and induced fever. Pretreatment of rabbits with 25 μg of the TNFRF significantly inhibited TNF‐α‐ and MDP‐induced sleep and fever responses. Finally, intravenously (i.v.) injected MDP enhanced NREMS, suppressed REMS, enhanced SWA, and induced fever; pretreatment of animals with the TNFRF injected centrally attenuated i.v. MDP‐induced sleep responses but not fever. These results suggest that the TNFRF acts as a TNF‐α antagonist in vivo and support the hypothesis that MDP‐induced sleep is partially mediated via brain TNF‐α.
Enhanced performance in elderly subjects following bright light treatment of sleep maintenance insomnia
Authors: MURPHY PATRICIA , CAMPBELL SCOTT
Published: November 2003

Sixteen older individuals with sleep maintenance insomnia were treated with night‐time bright‐light exposure (BL) while living at home. Twelve consecutive days of acute light treatment were followed by a 3‐mo maintenance light‐treatment period. Subjects completed laboratory evaluation sessions on five separate occasions (prior to and following the acute light‐treatment period, and once per month during the maintenance period). During each laboratory session, performance levels, sleep, and core body temperature were measured. The performance battery consisted of four computerized tasks (Logical Reasoning, Stroop Congruency, Two Letter Visual Search, and Wilkinson Four‐Choice Reaction Time) and was administered every 2 h between 10.00 and 18.00 hours. Subjects improved significantly on three of the four tasks from pre‐BL to post‐BL. During the maintenance period, subjects who received active BL treatment maintained significantly higher performance levels than a control BL group. Light treatment improved sleep efficiency and delayed the phase of the body temperature rhythm. Performance improvements were significantly related only to sleep and not to circadian phase. The implications for non‐circadian treatments of sleep maintenance insomnia and cognitive functioning in the elderly are discussed.
Respiratory and body movements as indicators of sleep stage and wakefulness in infants and young children
Authors: KIRJAVAINEN TURKKA , COOPER DAVID , POLO OLLI , SULLIVAN COLIN
Published: November 2003

Conventional polysomnographic (PSG) sleep staging to sleep staging based on a static‐charge‐sensitive bed (SCSB) recording in infants and young children was compared. The study consisted of whole‐night clinical sleep studies in 22 children at 24 weeks (SD 24, range 1–79 weeks) of age. Most of the children presented with respiratory disturbances during sleep. From the SCSB record, sleep stages were differentiated according to regularity of breathing, presence of body movements, and most important, presence of high‐frequency components of breathing (SCSB spikes). With both methods, three sleep/wake stages were distinguished: rapid eye movement (REM) sleep, non‐rapid eye movement (NREM) sleep and wakefulness. The average inter‐scorer reliability of the PSG sleep staging controlled in nine subjects was 88%. The average concordance between the two methods ranged from 82 to 85%, depending on the criteria used for scoring the SCSB. The mean sensitivity of the SCSB to detect NREM sleep ranged from 77 to 90% and the mean sensitivity to detect REM sleep ranged from 61 to 86%. The mean positive predictive value was 89–96% for NREM sleep and 54–67% for REM sleep. In conclusion, REM sleep is characterized by irregular breathing with superimposed fast respiratory movements. These changes are specific enough to allow distinction between episodes of NREM sleep, REM sleep and wakefulness with the non‐invasive SCSB method in infants and young children. Incomplete concordance between PSG and SCSB score was most frequently observed during sleep stage transition periods, where the behavioural state and electrophysiological criteria disagreed. When combined with the PSG, the SCSB provides complementary information about the behavioural state of child.
Correlates of sleep problems among men: The Vietnam Era Twin Registry
Authors: FABSITZ RICHARD , SHOLINSKY PHYLISS , GOLDBERG JACK
Published: November 2003

The Vietnam Era Twin (VET) Registry includes 14 800 male twins born 1939–55 and in military service in 1964–75. A mailed health survey including the Jenkins Sleep Questionnaire was sent to 11 959 members and 8870 (74.2%) provided responses on the frequency of sleep problems in the previous month. Prevalence of those experiencing conditions at least 1 day per month was 67.2% for waking often, 61.5% for waking tired/worn out, 48.1% for trouble falling asleep and 48.6% for awakening early. Ordinal logistic regression analysis was used to estimate sleep problems from demographic, behaviour and lifestyle characteristics, and morbid conditions. Black (vs. white) race, older age, church/religious group participation, social support, employment, cigarette smoking, light physical activity, and strenuous physical activity were associated with lower risk of one or more sleep problems. Eleven morbid conditions with a prevalence of 1% or more, coffee consumption, heavy alcohol consumption, and Framingham Type A behaviour pattern were associated with a higher risk of sleep problems. These analyses suggest that sleep problems may be one of the mechanisms relating reduced quality of life to many physical and behavioural characteristics. Fortunately, a number of the risk factors associated with sleep problems are lifestyle characteristics which, if modified, may reduce sleep problems.
Slow‐wave sleep: do young adult men and women age differently?
Authors: EHLERS CINDY , KUPFER DAVID
Published: November 2003

The differential effects of ageing on polysomnographic and EEG spectral characteristics of sleep were explored in men and women between the ages of 20 and 40. Men and women in their twenties were found to have similar percentages of slow‐wave sleep (SWS) (% Stage 3 and 4) and mean EEG slow wave activity (quantified by spectral analysis). Significant reductions in the percentage of SWS and mean slow wave activity over the night occurred in men during their thirties but not in the women. This suggests that gender difference in SWS may emerge between age 30 and 40 in young adults. Men in this sample were also found to have significant increases in Stage 2 sleep, and decreases in REM sleep time, REM activity, REM density and REM intensity. No significant effects of age were found for women in any visually scored sleep variables. Both men and women had age related reductions in spectral power in the spindle frequencies. Taken together, these findings suggest that the sleep of men and women over age 20–40 may age differently.
Effect of intracerebroventricular administration of α‐helical CRH (9–41) on the sleep/waking cycle in rats under normal conditions or after subjection to an acute stressful stimulus
Authors: Del C. GONZALEZ MONICA , VALATX J. L
Published: November 2003

It has been shown in a previous study that specific lesioning of the noradrenergic system of the locus coeruleus abolished the sleep increase induced by immobilization stress. Given the fact that brain corticotropin‐releasing hormone (CRH) acts as a neurotransmitter in the locus coeruleus under stress conditions, the present study was designed to investigate the involvement of CRH in the sleep increase seen after immobilization stress and on the spontaneous wake/sleep cycle. One hundred micrograms of the specific CRH receptor antagonist α‐helical CRH (9–41), or vehicle alone was injected into the right lateral ventricle 30 min either before subjecting the animals to immobilization stress or before the spontaneous sleep‐waking recordings onset. A single intracerebroventricular (i.c.v.) injection of α‐helical CRH (9–41) had no effect on spontaneous paradoxical sleep but abolished the stress‐induced increase, while wakefulness and slow‐wave sleep were unchanged under both normal and stressful conditions. We therefore report that the involvement of endogenous CRH in the paradoxical sleep mechanism is dependent on the environmental conditions and suggest that, while the paradoxical sleep increase induced by immobilization stress may be mediated by endogenous corticotropin‐releasing hormone, other mechanisms, either CRH‐independent or situated at a distance from antagonist activity, may be involved in spontaneous paradoxical sleep. These results show, for the first time, that endogenous CRH may be involved in sleep‐waking mechanisms only under stressful conditions and, in particular, as a fundamental component of the paradoxical sleep increase.
Comparison of three measures of quality of life outcome in the evaluation of continuous positive airways pressure therapy for sleep apnoea
Authors: JENKINSON CRISPIN , STRADLING JOHN , PETERSEN SOPHIE
Published: November 2003

Treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (NCPAP) has become a standard treatment since its introduction in 1981. Following such treatment the apnoeas disappear, sleep quality improves as apparently do daytime symptoms of sleepiness. Sleepiness is an unusual symptom and its impact on conventional indices of quality of life has rarely been measured. To allow comparison of NCPAP therapy with treatments for other conditions, measurements of quality of life before and after treatment using standard techniques are required. It is not clear which of the standard measures is most suited to measuring the health gain from nasal NCPAP, and indeed whether the disability of excessive sleepiness is included in all such measures. This study looks at three well recognized quality of life measures in OSA, before and after NCPAP therapy; the Short Form 36 (SF‐36), Functional Limitations Profile (FLP), and the EuroQol (EQ‐5D). The results were compared with data from normal populations. One hundred and eight patients with OSA undergoing a therapeutic assessment of NCPAP completed the three quality of life questionnaires before and 5 weeks after commencing treatment. Over 90 subjects completed all sections of the three measures on both occasions. The SF‐36 revealed substantial adverse effects on subjective health of OSA and that NCPAP treatment produced dramatic positive effects. For example, the effect sizes (difference in score, divided by SD of baseline score) in the Energy/Vitality dimension was 0.98 and for the overall Mental and Physical Component Scores, 0.76 and 0.57, respectively: an effect size over 0.5 is considered moderate and over 0.8 as large. The FLP data showed similar pre treatment decrements in quality of life and substantial improvements following NCPAP. The changes with treatment in the majority of the dimensions from both the SF‐36 and FLP were statistically significant (P<0.01). In contrast the EQ‐5D did not show significant improvements with therapy, presumably because of its failure to measure the aspects of quality of life related to severe sleep fragmentation and daytime sleepiness. In conclusion, this study has clearly shown considerable decrements in quality of life in patients with OSA, similar to other chronic disabling conditions. Furthermore, NCPAP therapy returns patients to a quality of life similar to the normal population.
Metamemory in narcolepsy
Authors: HOOD BERNADETTE , BRUCK DOROTHY
Published: November 2003

People with narcolepsy consistently report diminished memory function attributable to the disorder, however, objective evaluations of memory performance in this clinical group remain inconclusive. Previous evaluations of these subjective experiences have been primarily anecdotal with subjects required to provide global assessments of their memory function. The present study aimed to evaluate subjective assessments of memory dysfunction more extensively comparing responses by narcoleptics, subjects experiencing excessive daytime sleepiness, and controls, on the Metamemory in Adulthood (MIA) questionnaire. The results of the study indicate that subjects with narcolepsy have lower self efficacy for memory performance than either of the comparison groups, despite there being no significant difference between groups in relation to knowledge based aspects of memory functioning. This lowered self efficacy in narcolepsy is expressed through increased anxiety about memory function, decreased evaluations of memory capacity and increased perceptions of memory decline in relation to the comparison groups. It is argued that the negative cognitive self evaluations of narcoleptics potentially arise as a consequence of global psychosocial adjustment difficulties.
Effects of pentoxifylline and polymyxin B on the acute‐phase‐response to Escherichia coli endotoxin in dwarf goats
Authors: VAN MIERT A.S.J.P.A.M. , VAN DUIN C.T.M. , WENSING T.
Published: November 2003

The purpose of this study was to assess whether polymyxin B together with pentoxifylline, had beneficial effects on the acute‐phase‐response to E. coli endotoxin in the dwarf goat (n = 6). Polymyxin B partly neutralizes E. coli endotoxin by forming inactive polymyxin B‐lipopolysaccharide (LPS) complexes; pentoxifylline has been reported to suppress the LPS‐induced production of tumour necrosis factor (TNF‐α). E. coli LPS (0.0067 μg/kg/min over 30 min) induced fever, tachycardia, inhibition of rumen motility, a decline in WBC, lymphopenia, and decreases in plasma zinc and iron concentrations. Most of the haematological, blood biochemical and clinical effects of E. coli LPS were significantly reduced by polymyxin B pretreatment (0.1 mg/kg/min over 30 min, i.v.). Pentoxifylline (0.3 mg/kg/min over 30 min, i.v.) did not reduce the clinical and blood biochemical effects of E. coli LPS, however, it modulated the number of circulating neutrophils. No synergistic effects were observed after i.v. infusion of polymyxin B with pentoxifylline. The lack of synergy may be due to the production and release of pro‐inflammatory cytokines other than TNF‐α.
Pharmacology of the 5‐lipoxygenase inhibitors BAY Y 1015 and BAY X 1005 in the horse
Authors: Cunningham F. M. , Andrews M. , Landoni M. F. , Lees P.
Published: November 2003

Calcium ionophore A23187 induced time and concentration dependent pro‐duction of immunoreactive leukotriene (LT) B4 by equine heparinized whole blood in vitro. Time dependent production of immunoreactive LTB4 by equine neutrophils and immunoreactive LTC4 by equine eosinophils in vitro was also demonstrated. The 5‐lipoxygenase activating protein (FLAP) inhibitors, BAY X 1005 and BAY Y 1015, produced concentration dependent inhibition of ionophore‐induced LTB4 synthesis by equine whole blood (mean ± SEM IC50sn= 5; 6.14 ± 0.28 μm vs. 12.30 ± 0.75 μm for BAY Y 1015 and BAY X 1005, respectively) and neutrophils (mean ± SEM IC50sn= 5; 0.003 ± 0.001 μm vs. 0.045 ± 0.021 μm for BAY Y 1015 and BAY X 1005, respectively) and LTC4 synthesis by equine eosinophils (mean ± SEM IC50sn= 5; 0.0036 ± 0.0002 μm and 0.108 ± 0.023 μm for BAY Y 1015 and BAY X 1005, respectively) in vitro. In all three assays, BAY Y 1015 was more potent than BAY X 1005, and for both compounds much higher concentrations were required to inhibit LT synthesis by whole blood compared to isolated neutrophils and eosinophils. Plasma concentration–time relationships and pharmacokinetic parameters for BAY Y 1015 administered intravenously and orally to six horses at a dosage of 10 mg/kg in a two period cross‐over study were established. The study also evaluated the anti‐inflammatory properties of BAY Y 1015 and its ability to inhibit ex vivo whole blood LTB4 synthesis and in vivo LTB4 synthesis in a tissue cage model of acute inflammation. At this dosage, BAY Y 1015 failed to significantly inhibit immunoreactive LTB4 synthesis or the oedema produced by intradermal injection of the mild irritant, carrageenan.
Pharmacokinetics of ceftiofur and metabolites after single intravenous and intramuscular administration and multiple intramuscular administrations of ceftiofur sodium to dairy goats
Authors: COURTIN F. , CRAIGMILL A.L. , WETZLICH S.E. , GUSTAFSON C.R. , ARNDT T.S.
Published: November 2003

Twelve (12) lactating dairy goats (46–71 kg body wt at study initiation) were divided into four treatment groups and dosed with ceftiofur sodium at 1.1 mg ceftiofur free acid equivalents (CFAE)/kg or 2.2 CFAE/kg using a complete two route (intravenous, i.v.; intramuscular, i.m.), two‐period crossover design, with a 2‐week washout between injections. After another 2‐week washout period, the goats were dosed with ceftiofur sodium i.m. for 5 consecutive days at either 1.1 or 2.2 mg CFAE/kg. The goats from the 2.2 mg/kg multiple dose group were dried off and the i.v. kinetic study repeated. After all injections, blood samples were obtained serially for determination of combined serum concentrations of ceftiofur and metabolites. After intravenous doses of 1.1 and 2.2 mg/kg, the harmonic means of the terminal phase half‐lives were 171.8 and 233 min, respectively, for lactating does. The harmonic mean of the terminal phase half‐life after an i.v. dose of 2.2 mg/kg in non‐lactating does was 254 min. The AUC0–∞ was significantly less and the clearance significantly greater during lactation. After i.m. doses of 1.1 and 2.2 mg/kg, the harmonic mean terminal phase half‐lives were 163 and 156 min, respectively. The i.m. bioavailability of ceftiofur sodium in goats was 100%, and the AUC0–∞ was dose‐proportional from 1.1–2.2 mg CFAE/kg body weight. After five daily i.m. doses of ceftiofur sodium at either 1.1 or 2.2 mg CFAE, there was minimal accumulation of drug in serum as assessed by Cmax, and serum concentrations were dose‐proportional after the multiple dosing regimen.