bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface EMG reliability using spectral analysis
Authors: BUXBAUM J. , MYLINSKI N. , PARENTE F.R.
Published: November 2003

Several papers have recently appeared in the literature questioning the usefulness of surface EMG in the management of temporomandibular dysfunction (TMD) patients. One of the concerns is the stability of EMG over time in any one patient. This study was undertaken on normal subjects to determine the level of surface EMG stability over time using a variety of spectral analysis parameters. Four male and seven female subjects, ranging from 24 to 38 years of age, were selected for the study. All subjects had class I occlusions, intact dentition and no history of TMD. Oral and perioral hard and soft tissues were within normal limits. EMG data from the bilateral masseter muscles were obtained during four states of jaw activity: rest, right‐sided chewing, left‐sided chewing, and 50% maximal clench. Three sets of recordings were obtained in each study session. Three 10‐min study sessions were obtained for each subject. Six measures, which included SP‐50, central frequency, band width, effective band width, zero crossings and power spectrum, were analysed to assess their reliability and sensitivity over time during the several states of jaw activity. The conclusion of the study was that bilateral masseter EMG band width, effective band width, and power spectrum in normal humans are all reliable enough to be stable over a 6 week period, and sensitive enough to differentiate among jaw rest, right chewing, left chewing and 50% clench; power spectra being the most sensitive.
Reliability and validity of plain radiographs to assess angulation of small finger metacarpal neck fractures: Human cadaveric study
Authors: Lamraski G. , Monsaert A. , De Maeseneer M. , Haentjens P.
Published: November 2003

To quantify reliability and validity of plain radiographs for assessing the degree of small finger metacarpal neck fracture angulation, we created typical two‐fragments fractures in 30 adult cadaveric specimens. Reliability and validity of different radiographic measurement methods were determined by the intraclass correlation coefficient (ICC) and the Bland and Altman graphical approach. Intraobserver and interobserver reliability was high with any radiographic measurement method. Mean ICCs values (95% confidence intervals) varied from 0.76 (0.56–0.88) to 1.00 (0.99–1.00). The graphical approach confirmed good agreement. Validity was substantial when the fracture angle was measured between the line along the longitudinal axis of the metacarpal shaft and the line from the center of the metacarpal head to the fracture site on lateral radiographs. Mean ICCs values varied from 0.70 (0.36–0.86) to 0.79 (0.5–0.90). The graphical analysis also indicated good agreement. In contrast, considerable lack of validity was observed when the angle was measured on oblique radiographs. Although the mean ICCs values varied from 0.68 (0.12–0.88) to 0.74 (0.05–0.90), suggesting substantial correlation, the graphical analysis provided evidence for poor validity. There was systematic bias with oblique radiographs consistently producing higher readings (up to 35°). In summary, reliability and validity are good only when the degree of small finger metacarpal neck fracture angulation is measured after drawing lines on lateral radiographs. Oblique radiograph measurements consistently produce higher readings. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Towards a framework for clarifying psychiatric nursing roles
Authors: Machin T. , Stevenson C.
Published: November 2003

Psychiatric nurses function in many varied settings of practice, against the backdrop of continuous change, in the organization of health care delivery. Understandably, psychiatric nursing practice roles are not well‐defined despite the availability of a range of theories. A framework for brokering between theory and practice is proposed. Elements of role adequacy, role legitimacy and role support are related to ‘theory of’ and ‘theory for’ psychiatric nursing. When treated as dynamic in relation to one another, these elements can form a framework for clarifying practice roles.
Dual diagnosis of severe mental health problems and substance abuse/dependence: a major priority for mental health nursing
Authors: Gournay K. , Sandford T. , Johnson S. , Thornicroft G.
Published: November 2003

It is now established that very significant numbers of people with severe mental illness abuse or depend on drugs and/or alcohol. This combination (Dual Diagnosis) leads to increased rates of violence and service use, a reduction in adherence to treatment regimes, an increase in susceptibility to human immunodeficiency virus (HIV) infection and is now found in in‐patient populations. Because of their vulnerability to accidents and physical illnesses, dual diagnosis patients are found increasingly in accident and emergency departments, general medical wards and primary care settings. For this reason nurses and other health professionals working in general hospitals should be as aware as their mental health colleagues of the specific needs of this population. There are some excellent models of service organization and training for dealing with dual diagnoses populations in some parts of the USA. However, there is little such development in the UK. There are clear pathways to be followed, but the need for action is urgent.
When a client develops an attraction: successful resolution versus boundary violation
Authors: Schafer P.
Published: November 2003

Psychiatric mental health nursing in correctional institutes is an exciting field, presenting the correctional nurse with a number of challenges. A challenge of particular significance is that encountered when a client develops an attraction to a nurse. Nursing education traditionally has not equipped nurses with the theoretical knowledge or experience to address this phenomenon in clinical practice. Consequently, attractions may not be successfully resolved, resulting in boundary violations that leave the correctional nurse feeling battered. Although attraction in the therapeutic relationship is a well‐documented phenomenon in the psychosocial literature, nursing has not addressed this issue sufficiently. Only when the precipitating factors are defined clearly from a sociocultural context, which includes the profession and the correctional environment, can interventions for implementation be identified. The socialization of nurses, how nursing conceptualizes professionalism, gender issues, the atmosphere of the correctional environment and the potential for dual relationships that stem from the multiple roles of the nurse, are factors that the author contends contribute to a lack of boundary setting and maintenance in the nurse‐client therapeutic relationship. Consequently, this results in difficulties in assisting a client to resolve attraction successfully.
Schizophrenia: revisited
Authors: Provencher H. L. , Fournier J.‐P. , Dupuis N.
Published: November 2003

Schizophrenia is a devastating illness for the affected individuals and their families. Health care providers and researchers are also challenged by the clinical heterogeneity of this disorder. The goal of the present paper is to offer an updated overview of the aetiology, definition, clinical manifestations and pharmacological and psychosocial treatments of schizophrenia. Finally, some future directions for psychiatric nursing will be suggested in light of the existing knowledge of schizophrenia.
Smoking and schizophrenia
Authors: Forchuk C. , Norman R. , Malla A. , Vos S. , Martin M.‐L.
Published: November 2003

Individuals with schizophrenia have a high prevalence of smoking compared with the general population and little is known about why so many people with schizophrenia smoke. This paper reviews suggestions of differences in motivation for smoking. Possible explanations for smoking include psychological reasons, together with possible effects on positive and negative symptoms of schizophrenia and reduced side‐effects of neuroleptics. Understanding complex issues related to smoking and schizophrenia is important prior to developing health promotion strategies.
Burnout in psychiatric nursing: a meta‐analysis of related variables
Authors: Melchior M. E. W. , Bours G. J. J. W. , Schmitz P. , Wittich Y.
Published: November 2003

The purpose of this study was to describe the relative strengths of a number of variables on burnout among psychiatric nurses. A meta‐analysis of correlations revealed that burnout was negatively associated with job satisfaction, staff support and involvement with the organization and positively associated with role conflict. The results of the meta‐analysis were in line with results of other studies in which different populations were investigated. Therefore, the findings as such are not specific to psychiatric nurses. Based on the literature, three typical risk factors of burnout among psychiatric nurses were found: the patient group the nurse works with, such as patients who are aggressive and suicidal; the inequity in the exchange process between nurses and patients; and the unrealistic expectations of nurses of the patients' potential for rehabilitation.
Making our own meanings: a critical review of media effects research in relation to the causation of aggression and social skills difficulties in children and anorexia nervosa in young women
Authors: Barrett R. T. J.
Published: November 2003

This study examines concerns regarding the effects of video and television on certain types of behaviour. In the forefront of such debate is the claim by Elizabeth Newson [Newson E. (1994) Video violence and the protection of children. Journal of Mental Health3, 221‐227] that video and television representations of violence have a direct influence on children. Newson's argument is challenged in this paper, as is the popular belief that media images cause anorexia nervosa in young women. The author's argument against the notion of such direct influence is aimed at media effects research, which will be criticized as both deterministic and simplistic, on the grounds that as a positivist approach it overlooks the sophisticated resistance of viewers. Evidence from cultural studies, within an interpretivist tradition, will be cited as a challenge to the ‘moral panic of the media’, highlighting the incommensurability of diverse research disciplines. Mental health professionals have long been confronted with the failure of science to provide any unitary truth regarding the aetiology of mental health problems. Frustrating as that is, it is proposed that diverse empirical methods in the social sciences enrich debate and serve to expose the quest for a monocasual aetiology as fundamentally flawed. Media effects are thus only part of a myriad possible causes of anorexia nervosa, and yet are seen as central to current alarm regarding the way children learn (or don't learn) to cooperate with, and show concern for, other people.
Psychosocial problems in cancer care: a brief review of common problems
Authors: Bottomley A.
Published: November 2003

Worldwide the number of cancer cases continues to increase. Newly diagnosed patients often face more advanced and aggressive therapy as medical advances attempt to provide better survival outcomes. Success in part from improvements of treatment and from early diagnosis means that more cancer patients are living longer with the diagnosis. Given these facts, the following review provides a selective examination of the literature related to treatment problems. In addition, common problems of anxiety, depression, psychosexual and communications issues are examined. The uses of psychological interventions are briefly discussed, and approaches in which mental health nurses in cancer care can contribute to improvements in patient wellbeing are highlighted.
Carers as equal partners in care planning
Authors: Simpson R. G.
Published: November 2003

This was a pilot study that assessed the process and outcome of an initiative whereby carers of patients with dementia were given a designed package of documentation to hold at home. The research involved 20 carers of patients with dementia having carer‐held records at home for a 6‐month period. The aims of the research were: to assess carers' satisfaction with the system; to evaluate the actual use made of the documents by both carers and professionals; to assess the suitability of the document design; and to assess carers' roles as partners with professionals in care planning via use of the record. Both quantitative and qualitative data were obtained by use of a questionnaire that used quantitative scales of measurement and allowed carers to express views. The results showed that carers reported benefits of the system and felt more empowered and valued by service providers because of use of the documentation. However, there were design faults in the document itself, which were addressed as a result of the pilot study. A need for preparatory and on‐going education of clients and professionals was also identified regarding the best use of the document for all parties. A follow‐up three‐year longitudial study is planned in which health outcomes of the use of carer‐held records will be quantitatively measured. The problems identified in this pilot study will be addressed before the launch of the main study; several potential confounding variables have been recognized and can be controlled.
Conflict, consistency and fulfillment revisited: approaches to modelling the person
Authors: Clarke L.
Published: November 2003

The issue of consistency in human personality is reviewed. Attention is given to personality both as a fixed entity and as something mediated by situational factors. Mischel's reinvention of the person‐situation debate is noted as well as the seminal contributions of Allport, Eysenck and the ‘forgotten figure’ of Henry Murray. The discussion is resolved largely in favour of ‘the whole person’ in psychology but not before central issues of conflict, consistency and fulfillment are accounted for. In particular, the manner by which an evolving ‘scientific’ psychology chooses to ignore person psychology is seen to be pertinent. The topic is especially relevant to those psychiatric practitioners who espouse a whole person or ‘fulfillment psychology’ in their practice. However, the overall intention is to reintroduce material that extends the usual humanistic confines of the discussion.
Sleep apnoea and sympathetic nervous system activity: a review
Authors: COY TIMOTHY , DIMSDALE JOEL , ANCOLI‐ISRAEL SONIA , CLAUSEN JACK
Published: November 2003

A review was made of the literature relating sleep apnoea to sympathetic nervous system (SNS) activity, as inferred from catecholamine levels or muscle sympathetic nerve activity (MSNA). Twenty‐four studies were located. Most studies reported an elevation of norepinephrine and MSNA, both during sleep and wakefulness among individuals with sleep apnoea. However, studies rarely controlled for known confounders of sympathetic activity, making the validity of the findings questionable.
Sleepiness, snoring and driving habits
Authors: HANNING C.D. , WELSH M.
Published: November 2003

A self‐report postal questionnaire was sent to 5000 (3612 male) drivers randomly selected from the policy holders of an insurance company which insures only motorists who have achieved a maximum «no‐claims bonus». The questionnaire sought demographic and physical details (sex, age, height, weight and collar size), driving history (number of years, average mileage), accident history (number, number of «near misses»), frequency of events due to sleepiness (accidents, pulling off the road, falling asleep at the wheel), frequency and severity of snoring and sleep pattern and severity of EDS. Of the 2247 (44.9%) responses received, 1609 (44.5%) were male and 638 (46%) female. Snorers were more likely to report daytime sleepiness than non‐snorers and were more likely to have had to pull off the road due to sleepiness. Despite this increased sleepiness there were no significant differences in overall accident rate. These results were obtained from a population with a maximum «no‐claims bonus» which would have excluded any subjects who had already had a recent accident due to sleepiness. Thus the results probably underestimate the problem. It is concluded that snorers tend to be sleepier than non‐snorers and are more likely to have modified their driving habits as a result. Snoring and daytime sleepiness should be further investigated as contributory factors to road traffic accidents.
Sleepiness and performance in narcolepsy
Authors: HOOD BERNADETTE , BRUCK DOROTHY
Published: November 2003

Previous attempts to investigate the relationship between sleepiness and performance for subjects with narcolepsy have been limited by both the ability of narcoleptic subjects to contain their sleepiness for brief testing periods and the potential lack of sensitivity of routine performance tasks to sleepiness induced changes. The present study developed a research protocol which allowed subjects with narcolepsy to express states of sleepiness and non sleepiness and to then compare the performance of subjects with narcolepsy to age, gender and IQ matched controls on tasks evaluating automatic, attentional and complex cognitive functioning. The results indicated that at high arousal subjects with narcolepsy performed as well as controls on automatic tasks suggesting that the capacity to perform for narcolepsy subjects is not restricted by physiological factors but is secondary to the effects of sleepiness. Comparison of both the within subject effects for narcolepsy subjects of the transition between high and low arousal states, and the between subject effects of low arousal for narcolepsy subjects compared to controls indicate that complex cognitive tasks are the most sensitive to arousal fluctuation. This study provides support for the subjective experiences of subjects with narcolepsy of diminished cognitive function associated with the disorder.
Changes in direct current potentials during sleep deprivation
Authors: HOFFMANN ROBERT , BONATO RICHARD , ARMITAGE ROSEANNE , WIMMER FRANK
Published: November 2003

Previous research reported changes in steady‐state brain electrical activity during sleep. However, due to the quasi‐linear nature of the Direct Current (DC) changes, artifact contamination was a potential confound. The present study was performed to further explore DC potentials and to help establish its validity. Twenty‐five male university students (13 control and 12 sleep‐deprived; mean age 19 y (range 17–27 y) served as subjects. During wakefulness, subjects were tested every hour while standard EEG activity recordings were made, as well as DC measurement. Split plot analyses of variance (ANOVAs) revealed that changes in DC activity levels differed between the two groups. The control subjects showed the same pattern of decreasing DC observed previously with a return to baseline levels during waking hours. The sleep‐deprived subjects showed a smaller decrease in DC level through the night, followed by a rise in DC level that continued until the end of the 24 h study. It was concluded that DC measurement reflects changes in brain state associated with fatigue that are not attributable to artifactual processes.
Heart rate associated with sleep onset in preadolescent
Authors: PIVIK R.T. , BUSBY K.
Published: November 2003

It is well‐established that heart rate is decreased in NREM sleep relative to wakefulness, but the extent and progression of variations in heart rate when NREM sleep is first initiated, i.e. at sleep onset, have not been detailed. Furthermore, since physiological variations which have been documented during the sleep onset period have been based on studies of adult subjects, developmentally related influences on this process have not been examined. The present investigation addressed these issues by examining beat‐to‐beat (RR interval) changes in heart rate during the transitions between wakefulness, initial Stage 1, and subsequent Stage 2 sleep in normal and reading disabled male preadolescents who participated in a four‐consecutive‐night baseline sleep study. To avoid the influence of sleep deprivation or the effects of multiple sleep onset attempts, only initial, uninterrupted sleep onset periods from post‐adaptation nights were selected for study. For both groups the results indicated a significant slowing of heart rate beginning 30 s prior to Stage 1 onset, and a further decrease within 30 s of Stage 2 onset. In addition to providing new developmental data documenting heart rate variations in the wake/sleep transition, these results complement previous reports indicating motor and autonomic changes occurring in anticipation of Stage 1 onset. These data are also relevant to an ongoing controversy regarding whether initial Stage 1 or Stage 2 sleep should be considered as the time of sleep onset. To the extent that the systematic and coordinated variations across systems may be taken as an index of state change, and in the absence of remarkable differences in these variations between Stage 1 and subsequent Stage 2, the present data are most consistent with considering initial Stage 1 as the earliest EEG sign of physiological sleep onset.
Narcolepsy‐like symptoms among adult twins
Authors: KAPRIO J. , HUBLIN C. , PARTINEN M. , HEIKKILÄ K. , KOSKENVUO M.
Published: November 2003

The genetic architecture of narcolepsy is poorly known. Genetic and environmental components of symptoms characteristic of narcolepsy, excessive sleepiness and cataplexy were assessed in a population‐based sample of middle‐aged like‐sexed twin pairs. Questionnaire assessment of the 11‐item Ullanlinna Narcolepsy Scale (UNS), a validated screening instrument for narcolepsy [J. Sleep Res. (1994) 3, 52–59] and two subscales (sleepiness and cataplexy‐like symptoms) was obtained from both twins of 3785 pairs aged 33–60 y (541 male MZ pairs, 1089 male DZ pairs, 781 female MZ and 1374 female DZ pairs) from the population‐based Finnish Twin Cohort. For the UNS scores, the intraclass correlation for male MZ pairs was 0.365 and for male DZ pairs 0.072, while for female pairs the MZ correlation was 0.375 and for DZ pairs 0.155. Structural equation model fitting indicated that a model with additive and non‐additive genetic effects, and idiosyncratic environmental effects best accounted for the pattern of twin resemblance in both men and women. Genetic effects accounted for 35% (in men) and for 39% (in women) of total phenotypic variance in UNS. Analysis of the subscales suggested that there may be a greater genetic component to the sleepiness subscale, while environmental components play more of a role in the development of cataplexy‐like symptoms. Further investigation of the complex genetic architecture of narcolepsy and its symptoms is warranted.
Effects of CPAP treatment on psychological status in patients with severe obstructive sleep apnoea
Authors: BORAK JOANNA , CIEŚLICKI JAROSLAW , KOZIEJ MARCIN , MATUSZEWSKI ANDRZEJ , ZIELIŃSKI JAN
Published: November 2003

The aim of this study was to evaluate the effects of nocturnal continuous positive airway pressure (CPAP) breathing on the emotional status and cognitive function in 20 patients with severe obstructive sleep apnoea (OSA) (mean±SD apnoea/hypopnoea index=67±16, mean overnight arterial oxygen saturation=83±10%). Psychological tests were performed before, after three, and after twelve months of CPAP treatment. At initial investigation, amongst cognitive functions, the most disturbed were concentration and recent memory. The majority of subjects demonstrated increased mental stress, depression, and anxiety. Anxiety correlated with AHI (r=0.68). Mental stress correlated with AHI (r=0.56) and deficiency of Stage 2 NREM sleep (r=−0.55). CPAP treatment resulted in significant improvement in cognitive function; concentration, recent verbal, visual and spatial memory were already seen at three months. No improvement in IQ and in emotional status after three months and one year of treatment was found. It is concluded that in patients with severe OSA CPAP treatment results in a significant early improvement in cognitive function but not in emotional status.
Sleep during arousal episodes as a function of prior torpor duration in hibernating European ground squirrels
Authors: STRIJKSTRA ARJEN , DAAN SERGE
Published: November 2003

EEG's were recorded in hibernating European ground squirrels during euthermic arousal episodes at an ambient temperature of 5.5°C. Spontaneous torpor bouts ranged from 6 to 15 days, body temperature during torpor was 7.5°C. The torpor duration prior to EEG measurements was experimentally manipulated: the animals were induced to arouse by gentle handling after torpor of less then 1 day (n=3), 1–2 days (n=6), 3–4 days (n=9) and 5–12 days (n=9). The animals slept 71.5% of euthermic time, of which 61.4% NREM and 10.2% REM sleep. NREM percentage was slightly positively and REM percentage negatively correlated with prior torpor duration (TD). Spectral analysis showed changes in EEG activity during the euthermic phase in the slow wave frequency range (1–4 Hz) and in higher frequencies. Prior TD specifically affected the slow waves. Slow wave activity decreased exponentially during the euthermic phase. The initial slow wave activity showed a systematic increase with prior TD, which could be described by an exponentially saturating function, albeit with a relatively small time constant compared with spontaneous torpor duration. It is concluded that sleep during arousal episodes following torpor at an ambient temperature of 5.5°C is affected both in structure and intensity by prior TD. The results are consistent with the proposition that torpor inhibits the restorative function of sleep.
The alteration of human sleep and circadian rhythms during spaceflight
Authors: GUNDEL A. , POLYAKOV V.V. , ZULLEY J.
Published: November 2003

Numerous anecdotes in the past suggest the concept that sleep disturbances in astronauts occur more frequently during spaceflight than on ground. Such disturbances may be caused in part by exogenous factors, but also an altered physiological state under microgravity may add to reducing sleep quality in a spacecraft. The present investigation aims at a better understanding of possible sleep disturbances under microgravity. For the first time, experiments were conducted in which sleep and circadian regulation could be simultaneously assessed in space. Four astronauts took part in this study aboard the Russian MIR station. Sleep was recorded polygraphically on tape together with body temperature. For a comparison, the same parameters were measured during baseline periods preceding the flights. The circadian phase of body temperature was found to be delayed by about 2 h in space compared with baseline data. A free‐run was not observed during the first 30 d in space. Sleep was shorter and more disturbed than on earth. In addition, the structure of sleep was significantly altered. In space, the latency to the first REM episode was shorter, and slow‐wave sleep was redistributed from the first to the second sleep cycle. Several mechanisms may be responsible for these alterations in sleep regulation and circadian phase. Most likely, altered circadian zeitgebers on MIR and a deficiency in the process S of Borbély's sleep model cause the observed findings. The change in process S may be related to changes in physical activity as a result of weightlessness.
Sleep deprivation increases somatostatin and growth hormone‐releasing hormone messenger RNA in the rat hypothalamus
Authors: TOPPILA JUSSI , ALANKO LAURI , ASIKAINEN MARJUT , TOBLER IRENE , STENBERG DAG , PORKKA‐HEISKANEN TARJA
Published: November 2003

We studied the effect of sleep deprivation (SD) on the amount of somatostatin (SRIF) and growth hormone‐releasing hormone (GHRH) mRNA in rat hypothalamic nuclei. According to earlier studies SRIF possibly facilitates REM sleep and GHRH slow‐wave sleep. Adult male rats were sleep deprived by the gentle handling method either for 6 h during the first half of the light phase or for 12 h during the dark phase. Undisturbed rats sacrificed at the same time as the SD rats served as controls. After oligonucleotide in situ hybridization the amount of SRIF and GHRH mRNA was measured in brain sections by image analysis and cell count. SD increased the amount of SRIF mRNA in the arcuate nucleus (ARC). In the periventricular nucleus (PE) there was no effect. The amount of GHRH mRNA increased in the paraventricular nucleus (PA) in the 6 h SD group but no effect was detected in ARC. In the periventromedial hypothalamic area (pVMH) the amount of GHRH mRNA was higher in the control rats sacrificed in the morning (09.00 hours) than in the afternoon (15.00 hours), and SD had no effect. We conclude that SRIF cells in ARC and GHRH cells in PA are modulated by sleep loss, which is in accordance with the possible sleep regulatory function of these neuropeptides.
Anatomical and physiological considerations in thalamic rhythm generation
Authors: Huguenard John
Published: November 2003

The thalamus, known as the pacemaker for spindle rhythms in sleep, has several enabling features that promote such pacemaking. These include a circuitry that interconnects large groups of excitatory and inhibitory neurons, all of which are essentially capable of firing high‐frequency ‘bursts’ of discharges. Bursts in thalamic reticular neurons produce powerful inhibition in thalamic relay neurons, which leads to rebound excitation. The timing properties of the inhibition regulate the network activity by controlling rebound burst latency. Anatomical features within thalamus such as convergence and divergence determine the spread and synchronization of pacemaking activity. The anatomical basis of divergence, i.e. the degree of axonal arborization of elements within the thalamic circuit, can be functionally modified in a dynamic fashion by biochemical pathways that regulate the properties of synaptic release. These data suggest that it will be possible to therapeutically regulate the thalamus to modify not only the propensity to sleep but also forms of epilepsy that rely on similar thalamic circuitry.
Midazolam and ketamine induction before halothane anaesthesia in ponies: cardiorespiratory, endocrine and metabolic changes
Authors: Luna Stelio P. L. , Taylor Polly M. , Massone Flavio
Published: November 2003

Six Welsh gelding ponies were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) prior to induction of anaesthesia with midazolam at 0.2 mg/kg and ketamine at 2 mg/kg i.v.. Anaesthesia was maintained for 2 h using 1.2 % halothane concentration in oxygen. Heart rate, electrocardiograph (ECG), arterial blood pressure, respiratory rate, blood gases, temperature, haematocrit, plasma arginine vasopressin (AVP), dynorphin, ß‐endorphin, adrenocorticotropic hormone (ACTH), cortisol, dopamine, noradrenaline, adrenaline, glucose and lactate concentrations were measured before and after premedication, immediately after induction, every 20 min during anaesthesia, and at 20 and 120 min after disconnection. Induction was rapid, excitement‐free and good muscle relaxation was observed. There were no changes in heart and respiratory rates. Decrease in temperature, hyperoxia and respiratory acidosis developed during anaes‐thesia and slight hypotension was observed (minimum value 76 ± 10 mm Hg at 40 mins). No changes were observed in dynorphin, ß‐endorphin, ACTH, catecholamines and glucose. Plasma cortisol concentration increased from 220 ± 17 basal to 354 ± 22 nmol/L at 120 min during anaesthesia; plasma AVP concentration increased from 3 ± 1 basal to 346 ± 64 pmol/L at 100 min during anaesthesia and plasma lactate concentration increased from 1.22 ± 0.08 basal to 1.76 ± 0.13 mmol/L at 80 min during anaesthesia. Recovery was rapid and uneventful with ponies taking 46 ± 6 min to stand. When midazolam/ketamine was compared with thiopentone or detomidine/ketamine for induction before halothane anaesthesia using an otherwise similar protocol in the same ponies, it caused slightly more respiratory depression, but less hypotension. Additionally, midazolam reduced the hormonal stress response commonly observed during halothane anaesthesia and appears to have a good potential for use in horses.
Comparative pharmacokinetics of ampicillin trihydrate, gentamicin sulphate and oxytetracycline hydrochloride in Nubian goats and desert sheep
Authors: ELSHEIKH H.A. , OSMAN I.A. , ALI B.H.
Published: November 2003

In this investigation the pharmacokinetics of three commonly used antibiotics, ampicillin trihydrate (10 mg/kg), gentamicin sulphate (3 mg/kg) and oxytetracycline hydrochloride (5 mg/kg), given intravenously, were each studied in five Nubian goats and five desert sheep. The pharmacokinetic parameters were described by a two‐compartment open model. The results indicated that there were significant differences between the two species in some kinetic parameters of ampicillin and oxytetracycline but not gentamicin. Ampicillin elimination half life (t1/2β) in goats (1.20 h) was shorter than that in sheep (2.48 h), and its clearance (Cl) significantly higher in goats (2921mL/h·kg) compared to sheep (262 mL/h·kg) (P < 0.01). Ampicillin volume of distribution (Vdarea) was found to be significantly larger in goats (5673 mL/kg) than in sheep (992 mL/kg) (P < 0.01). For oxytetracycline, the t1/2β in goats (3.89 h) was significantly shorter than that in sheep (6.30 h) and the Cl value in goats (437 mL/h·kg) was significantly higher than in sheep (281 mL/h·kg). The results suggest that when treating sheep and goats, the pharmacokinetic differences between the two species must be considered in order to optimize the therapeutic doses of ampicillin and oxytetracycline.
Structure‐activity relationships between antibacterial activities and physicochemical properties of sulfonamides
Authors: Mengelers M.J.B. , Hougee P.E. , Janssen L.H.M. , Van Miert A.S.J.P.A.M.
Published: November 2003

Relationships between the antimicrobial activities of sulfonamides and physico‐chemical properties including the acid dissociation constant (pKa) and the hydrophobicity constant (π) were determined. The minimal inhibitory concentrations (MIC) of sulfonamides against Actinobacillus pleuropneumoniae, a gram‐negative veterinary pathogen, were used. High performance liquid chromatography was applied for the determination of the electronic and hydrophobic parameters. Empirically determined relationships pointed out the dominant role of the degree of ionization on the antimicrobial activity. The data indicate that hydrophobic properties of sulfonamides, characterized by π, are of minor importance for the in vitro antibacterial activity. Because of the restricted pKa range (4.9–7.7) it could not be established whether the relationship between pKa and activity was linear or bilinear. Whenever o,m‐disubstituted sulfonamides were included correlations decreased substantially. Relationships based on multicompartment equilibrium models were derived and indicated a bilinear relation between pKa and MIC. Model‐based equations showed that the antibacterial activity was governed by the extracellular ionic concentration of the sulfonamides whenever different intra and extracellular pH values were assumed in the equilibrium model. The antimicrobial activities of the sulfonamides against gram‐positive organisms were also related to the degree of ionization of the sulfonamides in the agar medium.
Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration: bioavailability and tissue residue studies
Authors: DELMAS J.M. , CHAPEL A.M. , GAUDIN V. , SANDERS P.
Published: November 2003

The pharmacokinetic properties of flumequine and its metabolite 7‐hydroxyflumequine were determined in six healthy sheep after single intramuscular (i.m.) and intravenous (i.v) injections at a dose of 6 mg/kg body weight. The tissue residues were determined in 20 healthy sheep after repeated i.m. administration with a first dose of 12 mg/kg and nine doses of 6 mg/kg. The flumequine formulation used was Flumiquil 3% Suspension Injectable®. The mean plasma concentrations of flumequine after i.v. administration were described by a three‐compartment open model with a rapid distribution and a relatively slow elimination phase. The low value of volume of distribution at steady state (Vdss) (0.52 ± 0.24 L/kg) and high value of volume of distribution (Vdλ3) (5.05 ± 3.47 L/kg) emphasized the existence of a small compartment with a slow rate of return to the central compartment. The mean elimination half‐life was 11.5 h. The 7‐hydroxyflumequine plasma levels represented 2.3% of the total area under the curve. The mean plasma concentrations of flumequine after i.m. administration were characteristic of a two‐compartment model with a first order absorption. The mean maximal plasma concentration (1.83 ± 1.15 μg/mL) was obtained rapidly, i.e. 1.39 ± 0.71 h after the i.m. administration. The fraction of dose absorbed from the injection site was 85.00 ± 30.13%. The minimal concentrations of flumequine during repeated treatment were significantly lower in females than in males. Eighteen hours after the last repeated i.m. admini‐stration, the highest concentration of flumequine was observed at the injection sites followed by kidney, liver, muscle and fat. The highest concentration of 7‐hydroxyflumequine was observed in the kidney and was ten times lower than the flumequine concentration. The longest flumequine elimination half‐life was observed in the fat.
Alpha‐adrenoceptors in equine digital veins: Evidence for the presence of both alpha1 and alpha2‐receptors mediating vasoconstriction
Authors: ELLIOTT J.
Published: November 2003

Rings of equine digital vein examined under conditions of isometric tension recording constricted to alpha‐adrenoceptor agonists with an order of potency of 5‐bromo‐6‐[2‐imidazolin‐2‐yl‐amino]‐quinoxaline bitartrate (UK 14304) = noradrenaline > 6‐Allyl‐2‐amino‐5,6,7,8‐tetrahydro‐4H‐thiazolo‐(4,5‐d) azepine (BHT‐920) > phenylephrine > dopamine > methoxamine. The maximum force generated was greatest for the non‐selective agonist noradrenaline and lowest for the alpha2‐selective agonist BHT‐920 with the other agonists between these two extremes. Selective inactivation of alpha1‐adrenoceptors (achieved by treating yohimbine‐protected tissues with phenoxybenzamine) reduced the maximum responses of all agonists, the EC50 values of UK 14304, BHT‐920 and noradrenaline and increased the EC50 values of phenylephrine and methoxamine. Prazosin (30 nM) had no inhibitory effect on responses to low concentrations of BHT‐920 and UK 14304 and caused competitive inhibition of responses to phenylephrine and noradrenaline giving pKb values of 8.49 ± 0.18 and 8.23 ± 0.14, respectively. Yohimbine (0.1 μM) caused significant competitive inhibition of responses to BHT‐920 and noradrenaline with calculated pKb values of 8.43 ± 0.11 for BHT‐920 and 7.43 ± 0.31 for noradrenaline and non‐competitive inhibition of responses to UK 14304. 2‐[2‐methoxy‐1,4‐benzodioxan‐2‐yl]‐2‐imidazoline (RX 821002; 10 nM) caused competitive inhibition of responses to BHT‐920 (pKb 9.04 ± 0.27) and dopamine (pKb 8.2 ± 0.2). These data indicate that equine digital veins possess both post‐synaptic alpha1 and alpha2‐adrenoceptors.
Pharmacokinetics and cardiopulmonary effects of guaifenesin in donkeys
Authors: Matthews N.s. , Peck K.e. , Mealey K.l. , Taylor T.s. , Ray A.c.
Published: November 2003

Five donkeys and three horses were given guaifenesin, intravenously, by gravity administration, until recumbency was produced. The time and dose required to produce recumbency, recovery time to sternal and standing were recorded. Blood samples were collected for guaifenesin assay at 10, 20, 30, 40, 50, 60 min, and 2, 3, 4 and 6 h after guaifenesin administration. Serum was analysed for guaifenesin using HPLC and pharmacokinetic values were calculated using a computer software package (RSTRIP). In donkeys, heart and respiratory rates and blood pressures were recorded before and at 5‐min intervals during recumbency. Arterial blood samples were collected before and at 5 and 15 min intervals during recumbency for analysis of pH, CO2, and O2. anova was used to evaluate dynamic data, while t‐tests were used for kinetic values.

Respiratory rate was decreased significantly during recumbency, but no other significant changes from baseline occurred. The mean (±SD) recumbency dose of guaifenesin was 131 mg/kg (27) for donkeys and 211 mg/kg (8) for horses. Recovery time to sternal (min) was 15 (SD, 11) for donkeys and 34 (SD, 1.4) for horses. Time to standing was 32 min for donkeys and 36 min for horses. Calculation of AUC (area under the concentration–time curve) (μg.h/mL) (dose‐dependent variable) was 231 (SD, 33) for donkeys and 688 (SD, 110) for horses. The clearance (CL) (mL/h.kg) was 546 (SD, 73) for donkeys, which was significantly different from 313 (SD, 62) for horses. Mean residence time (MRT) (h) was 1.2 (SD, 0.1) for donkeys and 2.6 (SD, 0.5) for horses. Volume of distribution Vd(area) (mL/kg) was 678 (SD, 92) for donkeys and 794 (SD, 25) for horses. At the rate of administration used in this study, donkeys required less guaifenesin than horses to produce recumbency, but cleared it more rapidly.
Interspecies allometric analysis of the comparative pharmacokinetics of 44 drugs across veterinary and laboratory animal species
Authors: Riviere J. E. , Martin‐Jimenez T. , Sundlof S. F. , Craigmill A. L.
Published: November 2003

The purpose of this study was to apply the method of allometric analysis to a study of the comparative disposition of veterinary drugs using the Food Animal Residue Avoidance Databank (FARAD) as a source of the comparative pharmacokinetic data. An initial filtration of the FARAD data was performed in order to exclude drugs for which no pharmacokinetic data were available, in at least four species the route of administration was other than intravenous, and the matrix was different from blood, plasma or serum. This process restricted the study to a total of 44 candidate drugs. The primary pharmacokinetic parameter selected for study was half‐life (t1/2). As this parameter is a composite of clearance (Cl) and volume of distribution (Vd), it was considered to be the most robust for interspecies scaling. Volume of distribution at steady state (Vdss) and clearance showed weak allometric correlations with weight across species. The relationships between body weight and elimination half‐life (t1/2β) were determined for this selected group of drugs by using the empirically determined function Y=a Wb. The function Y represents the parameter of concern (half‐life), a is a coefficient typical of every drug (intercept), W is the species average body weight, and b is the scaling exponent. A total of 11 drugs (tetracycline, oxytetracycline, chlortetracycline, erythromycin, diazepam, prednisolone, cephapirin, ampicillin, gentamicin, apramycin and carbenicillin) showed statistically significant correlations and consequently are excellent candidates for interspecies extrapolation of pharmacokinetic parameters (half‐life) in species of relevance to veterinary medicine. The remaining 33 drugs were divided into two groups which showed various degrees of lack of correlation. Many of the drugs that showed no allometric correlation were low hepatic extraction drugs. However, some other drugs demonstrated equivocal results which could either be due to a true lack of allometric correlation, or be inconclusive due to the lack of quality data or excessive variability due to the multi‐laboratory origin of the FARAD data. The results of this study show that interspecies scaling is applicable to certain veterinary drugs. The experimental determination of the coefficients of the allometric equation for relevant pharmacokinetic parameters (clearance and volume of distribution) could be an important tool in estimating dose in species where the drug has never been studied. This could have important consequences in terms of avoiding the use of dose‐titration studies in Phase I of drug development, for drugs that are experimentally ‘well behaved’.
Comparative plasma disposition kinetics of ivermectin, moxidectin and doramectin in cattle
Authors: Lanusse C. , Lifschitz A. , Virkel G. , Alvarez L. , SÁnchez S. , Sutra J. F. , Galtier P. , Alvinerie M.
Published: November 2003

The persistence of the broad‐spectrum antiparasitic activity of endectocide compounds relies on their disposition kinetics and pattern of plasma/tissues exchange in the host. This study evaluates the comparative plasma disposition kinetics of ivermectin (IVM), moxidectin (MXD) and doramectin (DRM) in cattle treated with commercially available injectable formulations. Twelve (12) parasite‐free male Hereford calves (180–210 kg) grazing on pasture were allocated into three groups of four animals each. Animals in each group received either IVM (Ivomec 1%, MSD AGVET, Rahway, NJ, USA), MXD (Cydectin 1%, American Cyanamid, Wayne, NJ, USA) or DRM (Dectomax 1%, Pfizer Inc., New York, NY, USA) by subcutaneous injection at a dose of 200 μg/kg. Jugular blood samples were collected from 1 h up to 80 days post‐treatment, and plasma extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The parent molecules were detected in plasma between 1 h and either 70 (DRM) or 80 (IVM and MXD) days post‐treatment. The absorption of MXD from the site of injection was significantly faster (absorption half‐life (t½ab) = 1.32 h) than those of IVM (t½ab= 39.2 h) and DRM (t½ab= 56.4 h). MXD peak plasma concentration (Cmax) was reached significantly earlier (8.00 h) compared to those of IVM and DRM (4–6 days post‐treatment). There were no differences on Cmax values; the area under the concentration–time curve (AUC) was higher for IVM (459 ng.d/mL) and DRM (627 ng.d/mL) compared to that of MXD (217 ng.d/mL). The mean plasma residence time was longer for MXD (14.6 d) compared to IVM (7.35 d) and DRM (9.09 d). Unidentified metabolites were detected in plasma; they accounted for 5.75% (DRM), 8.50% (IVM) and 13.8% (MXD) of the total amount of their respective parent drugs recovered in plasma. The comparative plasma disposition kinetics of IVM, MXD and DRM in cattle, characterized over 80 days post‐treatment under standardized experimental conditions, is reported for the first time.
PHENYLBUTAZONE PHARMACOKINETICS AND BIOAVAILABILITY IN THE DROMEDARY CAMEL (CAMELUS DROMEDARIUS)
Authors: Kadir A. , Ali B.H. , Al Hadrami G. , Bashir A.K. , Landoni M.F. , Lees P.
Published: November 2003

Phenylbutazone was administered intravenously and intramuscularly at a dosage rate of 4.4 mg/kg to a group of 6 female camels in a two‐period crossover study. After intravenous (i.v.) administration, disposition was characterised by a two‐compartment open model, with a low volume of distribution (0.174 l.kg–1), and distribution and elimination half‐lives of 0.43 and 12.51 h, respectively. After intramuscular (i.m.) dosing absorption was relatively rapid with absorption half‐time and time of maximal concentration values of 1.14 and 3.95 h, respectively. Plateau concentrations of phenylbutazone in plasma were obtained between 2 and 12 h and mean bioavailability was 97%, although this was subject to wide inter‐animal differences. Plasma concentrations of the phenylbutazone metabolite, oxyphenbutazone, were low after iv dosing and generally undetectable after im administration, indicating that it is unlikely to contribute significantly to the pharmacological effects produced by phenylbutazone administration. An indication was obtained that phenylbutazone inhibited the ex vivo synthesis of serum thromboxane B2 (TxB2) for 24 h after i.v. dosing, but this finding requires confirmation.