bluuebunny/crossref_metadata_2025 huggingface dataset:
The development and evaluation of a brief risk screening instrument for the psychiatric inpatient setting
Authors: Holdsworth  , Collis  , Allott
Published: March 2003

This paper reports on the development and evaluation of a risk screening instrument (RSI) intended for use by nursing staff on general acute psychiatric admission wards. The RSI comprised six questions concerning patient status on admission (e.g. sex, legal status, employment) and 11 items of judgement concerning the presentation of the patient (e.g. threatening behaviour, suicidality, family and social support). The inter‐rater reliability of the RSI was calculated to be 85% overall. The predictive value of the RSI was not confirmed when tested against harmful incidents subsequent to admission. However, the mean RSI score of that group of patients involved in harmful incidents tended to be higher than that group of patients not involved in such incidents, and all such incidents were found to occur within eight days of admission. Analysis of other data collected in the course of the study revealed discrete patient groups and provided systematic insights into their characteristics, which are potentially valuable when considering the nursing skills required on acute psychiatric inpatient units. It is concluded that the RSI tested has the potential to contribute to the assessment and management of risk within the acute psychiatric inpatient setting, by augmenting and guiding clinical judgement.
Melting straitjackets
Authors: Brandon
Published: March 2003

A description of the author's psychiatric breakdown is offered, and a discussion of how such wounded experiences can help in mental health work. Wounded healers are currently under attack in the National Health Service in the UK, following the Allitt affair. The author offers strong warnings against all forms of desiccated and detached professionalism in both nursing and social work. Material on Zen training, and how that relates to Shamanism, is discussed and Podvoll's Buddhist principles of ‘basic attendance’ are outlined.
Annie Altschul's legacy to 20th century British mental health nursing
Authors: Nolan
Published: March 2003

Being knowledgeable about, learning from and building upon one's history is the hallmark of an enlightened and progressive profession. This includes an appreciation of the work of those who contributed to moulding the profession into what it currently is. Mental health nursing has not distinguished itself by respect for its former leaders. In this paper, the life and times of one of the most outstanding mental health nurses of the century, Professor Annie Altschul, are recalled and examined. She sought constantly to establish what should be the essence of mental health nursing and what its role should be in the alleviation of human suffering. As an outsider herself, she identified strongly with those marginalized by society. Always a spokesperson for the centrality of nursing in patient care, she saw nurses as those best placed to provide holistic care to patients whilst other professionals specialized in their biomedical, social and financial needs. Long after her retirement, Altschul remains active in supervising and examining postgraduate nursing students. She is still a voice in the mental health debate, someone whose opinions are sought and valued.
Effective health care for people with learning disabilities: a formal carers’ perspective
Authors: Thornton C.
Published: March 2003

This paper explores the perceptions and experiences of formal carers, working in three different geographical locations in the south of England, in accessing primary health care for people with learning disabilities. The sample included six multidisciplinary, community learning disability teams and 11 managers of small homes for residents who had learning disabilities. Data were collected through focus group and individual semistructured interviews. Levels of collaboration between primary health care groups and the community learning disability teams and the managers of small homes were assessed. Questions were focused upon the importance of primary health care and the key care provider within the community setting. Although some good experiences were recorded, the overall levels of collaboration were poor. Health care was perceived as very important by all of the respondents. The general practitioner (GP) as the coordinator of health care was perceived as the normal model within our health care system but the majority of respondents questioned the effectiveness in relation to their own experiences of accessing health care for people with learning disabilities. The relocation of this role to the learning disability nurse was perceived as a possible solution.
A report of the development of a Chinese and British education initiative
Authors: Burnard P. , Arthur D. , Wang Z.
Published: March 2003

A significant event in the development of psychiatric and mental health nursing in China was conducted at An Ding Hospital, Beijing from May 5th to 9th 1999. The Peking Union Medical College, School of Nursing and An Ding Psychiatric Hospital hosted a series of workshops, conducted by Professor Philip Burnard (University of Wales), Dr David Arthur (Hong Kong Polytechnic University) and Madam Wang Zhiying (Director of the Nursing Department An Ding Hospital) for approximately 100 nurses from various regions of China.
Psychological needs of patients with HIV disease: reviewing the literature using Nichols' (1985) Adjustment Reaction Model as a framework
Authors: MURPHY M. , MELBY V.
Published: March 2003

Since the first manifestations of HIV infection presented in the United Kingdom in the early 1980s, there has been a dramatic increase in the incidence of HIV infection and a proliferation of diseases associated with HIV infection. HIV infection is now associated with physical, psychological, mental and neurological conditions. Many of these conditions are serious and pose a major threat to physical and mental health, with rapid deterioration of health status necessitating multiple hospital admissions to acute hospitals. The majority of people hospitalized with HIV diseases are currently being cared for on general wards. While physical needs are often well met, psychological needs are to a certain extent neglected. The literature cites numerous cases of neglect, discrimination and threats to confidentiality by helth professionals, including nurses. Such psychological needs, emanating out of hospitalization, compound existing psychological needs. Nichols' (1985) Adjustment Reaction Model describes a number of stages patients may go through during the course of their illness, and to some extent the patient's psychological needs can be traced throughout the trajectory of the disease. The purpose of this paper is to review the literature and present a theoretical argument, using Nichols' model as a framework, on psychological needs of patients with HIV diseases, and attempt to outline to what extent psychological needs of patients with HIV are met in institutional care. The authors recommend further research to determine nurses' perception of the importance of meeting psychological needs of patients with HIV disease.
Psychiatric nursing for promotion of mental health and prevention of depression in the elderly: a case study
Authors: HEDELIN B. , SVENSSON P.‐G.
Published: March 2003

The aim of this case study was to describe and analyse the basic pre‐conditions for an intervention programme focusing upon mental health promotion and prevention of depression in an elderly community group and to discuss the psychiatric nurse's community‐oriented health promotion work. The intervention programme, which was led by a psychiatric nurse, was built on intersectorial co‐operation between public and voluntary organizations, development of social networks to promote social support, and target group participation. The nurse's function in the community‐oriented work was to act at the individual, group and society level, as well as to mobilize resources among individuals and organizations, in order to create a favourable interaction, resulting in health and empowerment for the individual. Pre‐conditions for leading this work were: knowledge of health and mental ill health among the elderly, investigation methodology, knowledge about the local society, as well as pedagogical, supervisory and social competence.
A review of violence and personal injury legal cases in psychiatric and mental health nursing to identify a practical framework for risk assessment
Authors: Lemmer B.
Published: March 2003

Legal cases were analyzed that involved violence resulting in staff injury, patient assaults on staff, accidents involving the elderly, and patient self harm or injury where there was also an alleged breech in the duty of care. The study resulted in recommendations for: improved systems of work, including a practical framework to anticipate and recognize risk, with a case management approach to individual care, and supervisory procedures for vulnerable staff, explicit consent from patients and carers, and integrated recording of interdisciplinary methods for care.
Detecting nurse‐perceived patient treatment difficulty of psychiatric patients in hospital: an evaluation of a patient assessment sheet
Authors: Chiovitti R. F. , Gallop R.
Published: March 2003

Many changes have occurred in hospital psychiatric care, including decreased length of hospital stay and increased patient acuity. These changes highlight the need for nurses to adequately assess and formally document patient treatment difficulties. The purposes of this study were to determine the ability of the Patient Assessment Sheet (PAS) to predict patient ‘problems’ that psychiatric nurses perceived as associated with patient treatment difficulty, and to identify the patient problems missing from the PAS. These purposes were accomplished by comparing the PAS to the Hospital Treatment Rating Scales (HTRS). A correlational design and multiple linear regression technique were used. Eight psychiatric registered nurses assessed a total of 110 patients, admitted consecutively to one inpatient psychiatric unit. The HTRS and the PAS were used independently for each patient. Four PAS items (active affect, passive affect, aggression toward self, and patient confusion) significantly predicted 38% of the variance from the HTRS; and three HTRS items (isolation and withdrawal from relationships, noninvolvement in treatment, and wide variability in mood) significantly predicted 22% of the residual variance from the HTRS. The identified PAS and HTRS items help to make visible patient problems associated with nurse‐perceived patient treatment difficulty. This identification is potentially important for both clinical and political purposes.
The labyrinth of health as perceived by two groups of community nurses
Authors: Long Ann
Published: March 2003

The purpose of this research was to examine a group of 16 health visitors and a group of 16 community mental health nurses perceptions of health and health awareness. The study was mainly qualitative and exploratory in nature with some quantitative data being collected to condense the data. All 32 respondents were interviewed using a semistructured, tape recorded format. The content of the data was scrutinized and emerging patterns, themes, and concepts were noted and coded using a tried and tested theoretical process. The findings were related to the questions asked and comparisons were drawn between the information received from each group. An examination of the data revealed that the group of health visitors defined health terms of ‘functional’ states, described health in physical terms, and practised physical exercises as their health valuing behaviours in order to keep themselves healthy. This key theme also emerged with reference to their value of health at family and global levels. Taking their health for granted and being grateful for it when they saw someone in the community less well off than themselves was also highlighted as a major theme. The group of community mental health nurses defined their health in ‘being’ states and described health in a holistic manner. They perceived the value and concept of ‘freedom’ to be related to and embraced within the concept, definition and value of health at individual, family and global levels. They practised aesthetic health valuing behaviours to enhance their appreciation of health and self. Mental health, the ability to make choices, being self actualizing and the capacity to love and be loved were the key themes emerging throughout this group’s responses. It would be interesting to develop this research from a community health perspective.
Egalitarian consultation meetings: an alternative to received wisdom about clinical supervision in psychiatric nursing practice
Authors: Stevenson C. , Jackson B.
Published: March 2003

Clinical supervision (CS) has become a watchword for psychiatric nursing. Yet, there are contradictions and controversies in academic and professional discourse in relation to the nature of CS, both structure and process, its effectiveness and how this is ascertained, the preparation of supervisor and supervisee, and the quality of the supervisory relationship. The perception of such discord encouraged the authors of this paper to step outside the debate and enact a different kind of CS, which came to be known as egalitarian consultation (EC). Egalitarian consultation meetings (ECMs) were established with the postmodern turn in psychiatric nursing as a reference point. A space was created in which participants could construct their particular version of CS. The authors and six G‐grade community psychiatric nurses engaged with each other for six videotaped meetings. The data from the recordings were analysed using a hermeneutic grounded theory approach (Strauss & Corbin 1994), in keeping with the style of the research, which combined the roles of researcher and practitioner for the authors. The aim was to produce local knowledge of CS. The ECMs were characterized by a sense of freedom in relation to existing rules about hierarchy and truth. The participants, each as expert in her/his own case world, produced engrossing narratives about and for practice. The group developed a cohesiveness based in closeness and this encouraged radical talk and action – a questioning of practice systems. However, for some group members, radical equated to dangerous in terms of the watchful organization and a return to ‘real’ work (case supervision) was observed. Innovation in relation to CS may benefit from a change in institutional culture.
Education and research links between the UK and Thailand
Authors: Burnard P. , Claewplodtook P. , Pathanapong P.
Published: March 2003

Understanding the cultural contexts of training nurses in different countries is an important element for all nurse educators. In understanding other cultures we may be better prepared to understand our own. This paper identifies some similarities and differences between nurse education in Thailand and the UK. A notable difference is that ‘Thai culture’ is taught in Thai educational programmes whereas equivalent programmes are perhaps missing from UK colleges of nursing. The paper closes by identifying an on‐going research project into ‘academic levels in nursing’ that has been developed between the Royal Thai Army Nursing College, Bangkok and the School of Nursing and Midwifery Studies, University of Wales College of Medicine, Cardiff.
The use of discharge risk assessment tools in general psychiatric services in the UK
Authors: STEIN W. M.
Published: March 2003

Closure of asylums dismantled a system of risk control based on containment, resulting in a rise in homicides and suicides by discharged patients. Remedial action centred on a structured approach to managing multidisciplinary care (the Care Programme Approach) and a system of independent inquiries into homicides. A need for better discharge risk assessment was identified by government and health professions. The literature points to inherent limitations in the predictive power of actuarially based tools, restricting them to augmenting clinical judgement. This paper addresses the development and effective use of tools to predict risk to patients and public following discharge into the community. Methods used were: (i) a questionnaire to NHS Trusts in the UK; (ii) an analysis of documentation on tools in use; and (iii) interviews of hospital and community mental health teams at eight NHS Trusts. Findings point to: (i) a sporadic development of risk assessment tools at Trust level; (ii) that this has been stimulated by clinical governance but is unguided by any coherent national strategy; and (iii) that information technology for risk data collection is not well used in the UK, where there is reliance on use of paper records and informal communication. The implications for management and health professions are discussed.
Suspicion, resistance, tokenism and mutiny: problematic dynamics relevant to the implementation of clinical supervision in nursing
Authors: COTTRELL S.
Published: March 2003

In this paper I will discuss some of the more common pitfalls inherent in attempts to introduce clinical supervision to hospital wards or community teams. I will consider pre‐existing relationships and how these may, if unexamined and unaccounted for, result in clinical supervision becoming less than optimally effective. Drawing upon the theory of Transactional Analysis, in particular the concept of ‘psychological distance’, I consider four possible interpersonal dynamics and examine how these may impact upon the implementation of clinical supervision. These problematic dynamics can result in undue resistance, suspicion, tokenism or interpersonal difficulties. Finally, I will consider ways in which the aforementioned problems may be addressed and their effects minimized through the use of co‐operative contracting.
Reconciling voices
Authors: Casey B. , Long A.
Published: March 2003

There is a lack of nursing research in relation to how people with mental health problems make sense of their experiences of mental distress. Furthermore, few nursing related studies have conveyed service user's understandings and meanings for their experiences of mental ‘disorder’. Narrative psychology claims that people make sense of the world and their lives by using narrative structures to organize diverse experiences. By sharing these stories with others, interpretations are negotiated and personal and cultural meanings are formed. This study used a tried and tested approach to narrative analysis to analyse the transcribed narrative of one man, Gary, who was experiencing mental health problems. The study explores Gary's process of meaning making as it appears in his narrative; the frameworks and metaphors that he uses to help him make sense of his experiences. The tensions between Gary's internal voices and beliefs and the external voices of surrounding culture and psychiatry are highlighted. Emphasis is placed on the importance of attending and responding to personal meanings embedded in narratives as a means of developing sensitive nursing care and enriching nursing research.
Periodic limb movements and obstructive sleep apneas before and after continuous positive airway pressure treatment
Authors: Carelli G. , Krieger J. , Calvi‐Gries F. , Macher J. P.
Published: March 2003

Periodic limb movements during sleep (PLMS) and obstructive sleep apnea syndrome (OSAS) are two common sleep disorders. The similarity in periodicity of periodic limb movements (PLMs) and obstructive sleep apneas (OSAs) led us to hypothesize the existence of a common central generator responsible for the periodicity of both OSAs and PLMs.

In order to test this hypothesis, we compared apnea periodicity before continuous positive airway pressure (CPAP) treatment with PLMs periodicity during CPAP treatment in 26 OSA patients, consecutively recorded and treated in our sleep laboratory. The investigation on CPAP was performed twice, once during the initial evaluation and once during a follow‐up evaluation after 3 months of home treatment with CPAP.

Our results showed that, in this sample, 16 patients out of 26 had an association of OSAS and PLMS, defined as the occurrence of at least 5 PLMs per hour of sleep.

The mean apnea interval – measured as the time between the beginning of two successive apneas – was 43.1 s (±15.2, SD) and the mean PLM interval – calculated in the same way – was 29.6 s (±15.2) during the baseline night, 28.5 s (±15.7) during the first CPAP night, and 29.8 s (±14.8) during the second CPAP night. Thus, the periodicity of the two phenomena (apneas and PLMs) was different, both before and after CPAP treatment (P< 0.05).

When considering the interval between the end of an event (apnea or PLM) and the beginning of the next one the mean apnea interval was 19.5 s (±11.6), and the mean PLM interval was 28.1 s (±15.3) during the untreated night, 26.6 s (±16) during the first CPAP night and 27.9 s (±15) during the second CPAP night. The shortening of apnea intervals with this method of measuring intervals reflects the longer duration of apneas as compared to PLMs. Again the intervals between PLMs were not different between each other but the intervals between apneas were different from the intervals between PLMs (P< 0.05)

These results show that the periodicity of PLMs is different from that of OSAs, suggesting that sleep apneas and PLMs are not generated by a common central generator.
Effect of the 5‐lipoxygenase inhibitor, fenleuton, on antigen‐induced neutrophil accumulation and lung function changes in horses with chronic obstructive pulmonary disease
Authors: Marr K.A. , Lees P. , Page C.P. , Cunningham F.M.
Published: March 2003

The leukotrienes (LT) LTD4 and LTB4 have been shown to cause bronchoconstriction and neutrophil accumulation, respectively, in horse lungs. Such changes are characteristic of the equine allergic respiratory disease, chronic obstructive pulmonary disease (COPD). To further investigate the role of these putative mediators in the pathogenesis of equine COPD the effect of a 5‐lipoxygenase inhibitor, fenleuton, on antigen‐induced changes in horses with this condition has been examined. Six horses with COPD underwent a series of four antigen challenges, one month apart, with placebo pre‐treatment on three occasions and fenleuton (4 days oral dosing 5 mg/kg) pre‐treatment on one occasion. Three horses received fenleuton prior to the second challenge and three horses received the drug prior to the fourth antigen challenge. Changes in radiolabelled neutrophil distribution, lung function and peripheral leucocyte counts were monitored on each occasion for 7 h following the start of antigen challenge. Antigen challenge caused an increase in radioactive counts over the lungs and a decrease in peripheral leucocyte count. Neither response was affected by fenleuton pre‐treatment. Mean maximal changes in pleural pressure (ΔPplmax) and respiratory rate were also unaffected by fenleuton pre‐treatment. However, in the two horses which responded to antigen‐challenge with a particularly marked increase in ΔPplmax (>15 cm H2O), prior administration of fenleuton reduced the response by 64 and 63%. These results suggest that 5‐lipoxygenase inhibitors warrant further investigation as bronchodilators in equine COPD.
Femtomolar bradykinin‐induced relaxation of isolated bovine coronary arteries, mediated by endothelium‐derived nitric oxide
Authors: Nakamura  , Kawagoe  , Obi  , Miyamoto  , Ishiguro  , Nishio
Published: March 2003

We reported previously that bradykinin induces endothelium‐dependent relaxation at nanomolar (n M) concentrations in isolated bovine coronary arteries with an intact endothelium. Recently we have found that in the presence of 10 μm indomethacin, femtomolar (f
M) concentrations of bradykinin induce endothelium‐dependent relaxation in some bovine coronary arteries (≈ 10% of the coronary arteries examined). The present study was designed to characterize the relaxation induced by f
M bradykinin. Relaxation was completely abolished by repeated application of f
M bradykinin, by 100 μm Nω‐ nitro‐
l‐ arginine methyl ester and by 10 μm methylene blue. Relaxation induced by n
M bradykinin was partly affected by these treatments. Relaxation induced by both concentrations of bradykinin was inhibited by a B2‐kinin receptor antagonist, [Thi5,8, D‐Phe7]‐bradykinin, in a concentration‐dependent manner, but not by a B1‐kinin receptor antagonist, des‐Arg9, [Leu8]‐bradykinin. In the presence of 10 μm captopril, an angiotensin‐converting enzyme (ACE) inhibitor, all coronary arteries examined in this experiment showed endothelium‐dependent relaxation to f
M bradykinin. These results show that some bovine coronary arteries relax in response to f
M bradykinin, and this response is mediated predominantly by the release of nitric oxide via stimulation of endothelial B2‐kinin receptors. The relaxation may be dependent on ACE activity.
Biliary elimination kinetics and tissue concentrations of oxytetracycline after intravenous administration in hens
Authors: Serrano  , Moreno  , Rosado  , Guimer  , Escudero
Published: March 2003

The pharmacokinetics of the biliary elimination of oxytetracycline (OTC) and tissue concentrations in certain organs were studied in 10 Leghorn hens. The animals were anaesthetized using xylazine/ketamine administered by the intramuscular (i.m.) route and were immobilized for right laparotomy. Both bile ducts were cannulated and a dose of 20 mg/kg of oxytetracycline hydrochloride was administered intravenously (i.v.). Samples of bile excreted were taken at predetermined intervals during 6 h. At 6 h animals were slaughtered and tissue samples of blood, liver, kidney, pancreas, spleen, heart, lung and pectoral muscle were taken.

 The values for OTC biliary elimination rate times were best fitted to a one‐exponential equation. The maximum value for OTC biliary excretion rate (3.69 ± 0.6 μg/min/kg) was reached at ≈ 17.5 min (time to maximum concentration (tmax)). The first‐order rate constant for the biliary excretion (k) and the half‐life (t1/2) were 6.7 × 10−3 min−1 and 110.55 min, respectively. The mean value of area under the biliary excretion rate time curve (AUC) indicated that 839.77 μg/kg body weight (b.w.) were eliminated by the biliary route. The cumulative biliary excretion data indicated that ≈ 4.20% of the dose was eliminated by this route, 3.28% being eliminated during the first 6 h and 0.92% thereafter. The highest mean concentrations were found in the kidney (35.82 μg/kg) and liver (16.77 μg/g). Significant differences were found between the concentrations of the various tissues studied. Plasma concentration was lower than that of the other tissues (except lung).
The effect of sex on antipyrine metabolism in cattle at different ages
Authors: Janus K. , Antoszek J.
Published: March 2003

The aim of this study was to determine the effect of sex on the metabolism of antipyrine by measuring the antipyrine plasma clearance as well as excretion of three major metabolites in urine in cattle of different ages.

 The experiment was carried out on 10 female and 10 male cattle of Black and White breed. The antipyrine test was carried out at 1, 2, 4, 6, 8, 12 and 18 months of age for each animal (single dose of 10 mg/kg antipyrine were given intravenously). The concentrations of antipyrine, 4‐hydroxyantipyrine (4‐OHA), 3‐hydroxymethylantipyrine (HMA) and norantipyrine (NORA) were measured in plasma and urine by high performance liquid chromatography (HPLC).

 The apparent volume of distribution of antipyrine (aVd) decreased significantly between 1 and 18 months of age, but mean aVd values observed in males and females were not statistically different. The experimental period was charac‐terised by a steady decrease (statistically significant) in antipyrine half‐life (t1/2β). These values did not differ significantly between males and females under 12 months. In 12 and 18 month‐old animals the antipyrine half‐life in the females was significantly shorter than in the males. The systemic clearance (Cls) of antipyrine increased significantly between 1 and 18 months of age. No significant differences were observed between systemic clearance of antipyrine in males and females under 12 months. In 12 and 18 month‐old animals the Cls values were significantly higher in females than in males. Following intravenous administration, recovery of antipyrine and its three main metabolites increased significantly with age. These values did not differ significantly between males and females under 12 month of age. In 12 and 18 month‐old females the excretion of 4‐OHA and HMA in urine was significantly higher than in males at the same age. The excretion of NORA and unchanged antipyrine in males and females did not differ significantly. The partial clearances of antipyrine metabolites (Clm) increased significantly between 1 and 18 months of age. No significant differences were observed between Clm values in males and females under 12 months of age. In 12 and 18 month‐old females the partial clearances of 4‐OHA and HMA were significantly higher than in males. The clearance of NORA was significantly higher in 18 month‐old females than in males.

 In conclusion, we report a sex‐linked difference in plasma antipyrine clearance and urinary excretion of the main metabolites of antipyrine in cattle over 12 months of age, the females being the more active metabolizers.
Non‐linear pharmacokinetics of ofloxacin after a single intravenous bolus dose in pigs
Authors: Son D.‐S. , Ikenoue N. , Tagawa Y. , Shimoda M. , Kokue E.
Published: March 2003

The pharmacokinetics of ofloxacin (OFLX) was investigated after intravenous administration of 3, 10 and 30 mg/kg of body weight in pigs. Plasma OFLX concentration–time course collected from the highest dosage showed a convex decline, indicating a capacity‐limited process in drug elimination (Michaelis–Menten elimination). Dose–normalized area under curve (AUC/Dose) and mean resident time (MRT) were dose‐dependent, indicating a classical pattern of non‐linear elimination pharmacokinetics. Based on simultaneous curve fitting from three doses, non‐linear pharmacokinetic parameters were as follows: 0.87 mg/h/kg for maximum velocity, 2.20 μg/mL in Michaelis–Menten constant and 2.06 L/kg for apparent volume of distribution. Based on a model‐independent analysis, the apparent volume of distribution at steady‐state (Vdss) was dose‐independent whereas total body clearance (CLtot) was dose‐dependent, mainly contributed by renal clearance (CLr) with the regression line of CLtot=1.14×CLr+0.09 (r=0.92). The intercept of the regression line indicates non‐renal clearance (CLnr), corresponding to the value of observed CLnr without dose‐dependency. Because of a higher CLr compared with glomerular filtration rate (GFR) in spite of drug reabsorption, the CLr must contain the renal active tubular secretion. With increasing dosage, the level of saturation of tubular secretion of OFLX decreased the CLr, resulting in the decrease in CLtot. The plasma protein binding to OFLX was dose‐independent: mean free fraction (fp)=0.73, with probably no influential effect on OFLX disposition. In conclusion, the degree of saturation in the renal active tubular secretion of OFLX could be a major causal factor in the alteration of CLr in an increasing dosage of OFLX. Accordingly, the alteration of CLr could directly induce the non‐linear pharmacokinetics of OFLX in pigs, an important consideration in clinical therapeutics.
A field comparison of the efficacy and tolerance of marbofloxacin in the treatment of bovine respiratory disease
Authors: Thomas E. , Caldow G. L. , Borell D. , Davot J. L.
Published: March 2003

A multicentre, controlled, randomized and blinded trial was carried out in 180 ruminating calves with pyrexia and respiratory sign(s) on nine Belgian, British and French farms. All animals were sampled for pathogenic bacteria before treatment and at failure/relapse. Calves were injected with either marbofloxacin (M) solution [Marbocyl® (Laboratoire Vétoquinol, Lure, France) 10%] at 2 mg/kg/24 h for 4 days intravenously on the first day then subcutaneously, or tilmicosin (T) solution (Micotil®, Elanco Products Ltd, Basingstoke, Hants, UK) at 10 mg/kg as a single subcutaneous (s.c.) injection. The animals were examined clinically eight times up to day 28. The bacterial pathogens were found to be sensitive to marbofloxacin: for Pasteurella haemolytica the minimum inhibitory concentration (MIC)90 was 0.08 μg/mL and for P. multocida the MIC90 was 0.04 μg/mL. Cure rates at day 4 for group M and group T were 84 vs. 82%, respectively (P ≥ 0.05). However, overall clinical score was significantly lower after 1 day in group M (P < 0.05). There was no difference in either relapse rate or average daily weight gain between groups. Marbofloxacin was found to be better tolerated than tilmicosin at the s.c. injection site (77.5 vs. 42.2% calves without local swelling, P=0.001) and was well tolerated when injected intravenously. Marbofloxacin was shown to have comparable but faster efficacy and better local tolerance than tilmicosin in the treatment of bovine respiratory disease (BRD).
Pharmacokinetics and microsomal oxidation of praziquantel and its effects on the P450 system in three‐month‐old lambs infested by Fasciola hepatica
Authors: Giorgi M. , Salvatori A. P. , Soldani G. , Giusiani M. , Longo V. , Gervasi P. G. , Mengozzi G.
Published: March 2003

Giorgi, M., Salvatori, A. P., Soldani, G., Giusiani, M., Longo, V., Gervasi, P. G., Mengozzi, G. Pharmacokinetics and microsomal oxidation of praziquantel and its effects on the P450 system in three‐month‐old lambs infested by Fasciola hepatica. J. vet. Pharmacol. Therap.24, 251–259.

Praziquantel (PZQ) is a broadly effective trematocide and cestocide, widely employed in veterinary and human medicine. In view of several differences in both its pharmacokinetic profile in different animal species and in the cytochrome P450‐dependent system between ruminant and nonruminant species, the present study was undertaken to determine the pharmacokinetics of this drug, its effects on the P450 system and the involvement of cytochrome P450 in its metabolism in 3‐month‐old lambs infested by Fasciola hepatica. Following both oral and i.m. administration, PZQ disposition was best described by a linear one‐compartment open model with a rapid absorption and elimination. Although the PZQ dose used by the i.m. route was only half of that used by the oral route, the mean PZQ plasma concentration was higher after i.m. than after oral treatment. Oral treatment with 30 mg/kg/day of PZQ did not modify the mono‐oxygenase activities tested, whilst the administration of PZQ at a dose of 60 mg/kg/day for 2 days caused a significant decrease in the P450 3A‐dependent erythromycin N‐demethylase and 6β testosterone hydroxylase activities. From the incubation of microsomes from lambs not treated with PZQ, a single metabolite (PZQ 11b‐OH or PZQ 1‐OH) was identified by GC/MS analysis. By selective inhibition of the 3A subfamily performed with triacetyloleandromycin, the production of this metabolite declined by about 90% suggesting a prominent role of P450 3A isoforms in this oxidation. These features indicate that agents or drugs which are able to modulate P450 3A‐dependent catalysis may interfere with the metabolism, bioavailability and therapeutic effects of PZQ.
Pharmacokinetics of sarafloxacin in pigs and broilers following intravenous, intramuscular, and oral single‐dose applications
Authors: Ding H. Z. , Zeng Z. L. , Fung K. F. , Chen Z. L. , Qiao G. L.
Published: March 2003

Pharmacokinetics of sarafloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of 5 (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analysed by a noncompartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half‐lives (t1/2β) were 3.37 ± 0.46, 4.66 ± 1.34, 7.20 ± 1.92 (pigs) and 2.53 ± 0.82, 6.81 ± 2.04, 3.89 ± 1.19 h (broilers), respectively. After i.m. and p.o. doses, bioavailabilities (F) were 81.8 ± 9.8 and 42.6 ± 8.2% (pigs) and 72.1 ± 8.1 and 59.6 ± 13.8% (broilers), respectively. Steady‐state distribution volumes (Vd(ss)) of 1.92 ± 0.27 and 3.40 ± 1.26 L/kg and total body clearances (ClB) of 0.51 ± 0.03 and 1.20 ± 0.20 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), mean residence times (MRT), and mean absorption times (MAT) were also determined. Sarafloxacin was demonstrated to be more rapidly absorbed, more extensively distributed, and more quickly eliminated in broilers than in pigs. Based on the single‐dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 10 mg/kg given intramuscularly every 12 h in pigs, or administered orally every 8 h in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 μg/mL.
Challenges associated with the evaluation of veterinary product bioequivalence: an AAVPT perspective
Authors: MARTINEZ M. , LANGSTON C. , MARTIN T. , CONNER D.
Published: March 2003

Martinez M., Langston C., Martin T., Conner D. Challenges associated with the evaluation of veterinary product bioequivalence: an AAVPT perspective.J. vet. Pharmacol. Therap.25,201–220.

The Generic Animal Drug Patent Term Restoration Act (GADPTRA) enacted in 1988 provided the same benefits to animal drug products that were granted to human generic products. It has been over 13 years since the GADPTRA was enacted, and veterinary drug sponsors and regulators have gained enormous insight and experience into some of the unique challenges associated with the determination of product bioequivalence for veterinary dosage forms. Moreover, advances in information and technology have opened both new issues that must be addressed and new mechanisms for demonstrating product bioequivalence. While many aspects of the existing Center for Veterinary Medicine Bioequivalence Guidance continue to provide invaluable guidance to the animal drug industry, there are also aspects of this guidance that are being called into question. Therefore, during the 2001 annual meeting of the American Academy of Veterinary Pharmacology and Therapeutics, participants were asked to address issues and concerns associated with the evaluation of veterinary product bioequivalence. This manuscript provides a summary of the concerns and discussions that transpired.
Management of hepatitis C
Authors: Moussalli J. , Opolon P. , Poynard T.
Published: March 2003

Chronic hepatitis C is a major health care problem throughout the world. The disease may progress to cirrhosis, with complications such as hepatocellular carcinoma. The usual primary goal of therapy is viral eradication, as patients with long‐term remission are generally regarded as unlikely to develop cirrhosis or hepatocellular carcinoma. Another primary goal should be the reduction in liver fibrosis progression. Interferon‐α (IFN‐α) is the only drug approved for the treatment of hepatitis C in Europe and North America. Its effectiveness appears to be related to dose and duration of therapy. The best efficacy/risk ratio seems to be in favour of 3 million units (MU) IFN‐α three times per week on a 12‐month schedule. With this regimen, a sustained alanine aminotransferase (ALT) response is achieved in nearly 35% of patients. Ribavirin has emerged as potentially the second most effective drug. While it appears unsatisfactory when given alone, it seems much more effective in combination with IFN. Combining them seems to exert a synergistic effect between the two drugs and sustained remission might be achieved in nearly 50% of patients with combination therapy. Controversy persists concerning the long‐term benefit of therapy in transient responders and non‐responders. It is possible that IFN therapy, in comparison to natural history, might reduce liver fibrosis progression and prevent hepatocellular carcinoma, even in non‐responders, and have greater efficacy if used in long‐term treatment. Whatever the treatment schedule, prolonged viral eradication may not be achieved in all patients and new drugs should be sought to improve the results of therapy.
Statistical models for predicting a beneficial response to interferon‐α in patients with chronic hepatitis B
Authors: Lau D. T.‐Y. , Comanor L. , Minor J. M. , Everhart J. E. , Wuestehube L. J. , Hoofnagle J. H.
Published: March 2003

Therapy with interferon‐α has been reported to induce remissions in 35% of patients with chronic hepatitis B. The ability to identify patients likely to respond would be helpful in making recommendations for treatment. In this statistical analysis we included 82 patients with chronic hepatitis B who received interferon‐α in clinical trials at the National Institutes of Health between 1984 and 1991. A response was defined as the loss of hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) within 1 year of therapy. Multiple clinical parameters measured at pretreatment (month 0) and after the first month (month 1) of therapy were selected by stepwise regression to support the development of the prognostic models: the two‐stage logistic regression model and a neural network that utilized higher‐order non‐linear interactions between variables. Among the 82 patients, 24 (29%) were responders. The two‐stage logistic model using pretreatment variables: sex, hepatic fibrosis and alanine aminotransferase (ALT) levels correctly identified 61% of responders and 76% of non‐responders. When HBV DNA at month 1 along with sex, initial ALT and fibrosis was included, the resultant model correctly identified 69% of responders and 77% of non‐responders. The neural network, by incorporating interactions between variables, correctly identified 77% and 86% of responders, and 87% and 92% of non‐responders, using pretreatment factors alone and the combination of pretreatment and month 1 factors respectively. Hence, the neural network was more accurate than the simple logistic regression model in predicting a response to interferon‐α in chronic hepatitis B. The universality of these models needs to be further verified.
Prospective virological follow‐up of hepatitis C infection in a haemodialysis unit
Authors: Halfon P. , Khiri H. , Feryn J. M. , Sayada C. , Chanas M. , Ouzan D.
Published: March 2003

Hepatitis C virus (HCV) is of major concern in the management of patients on maintenance haemodialysis. Many studies have reported a high prevalence of HCV infection in dialysis centres. The objective of our study was first, to perform a prospective follow‐up of the evolution of HCV infection in a haemodialysis centre, and second, to assess the rate of viral clearance in patients on dialysis. For this, genotypes, HCV antibodies (anti‐HCV) and HCV RNA were evaluated initially and 9months later. HCV RNA quantification was also performed. Of 136 patients, 62 (45.6%) were anti‐HCV positive by third‐generation enzyme immunoassay (EIA3) in the first survey and 64 of 136 (47.1%) were anti‐HCV positive by EIA3 in the second survey. The rate of new HCV infection, estimated from the two seroconversions between the surveys, was 1.9% per year. One of the two patients was initially HCV RNA positive, with a titre of 0.6×106eqml–1. The viral load measured in the dialysis patients was low and does not seem to be influenced by dialysis. No significant difference was observed in viral load between the two periods nor were there any gender‐related differences in viral load. In conclusion, detection of antibodies to HCV, together with HCV RNA, seems to be relevant in haemodialysis patients, but this strategy is not suitable for use in all haemodialysis centres because of its high cost.
Identification of novel sequences at the 5′ terminus of the hepatitis C virus genome
Authors: Trowbridge R. , Gowans E. J.
Published: March 2003

To permit accurate identification of the 5′ end of the HCV genome, we used RNA ligase‐mediated rapid amplification of cDNA ends (RLM‐RACE) where an RNA molecule of known sequence (transcribed invitro from a cDNA template) was ligated to RNA purified from a hepatitis C virus (HCV)‐infected liver sample. After ligation, the product was amplified by nested polymerase chain reaction (PCR) and amplicons that were equal to or greater in size than those predicted from the recognized 5′ terminus of the HCV genome were cloned into pBluescriptKS. Twelve clones were sequenced, including three that were identical and contained an additional eight nucleotides, namely CCCCCCCA. Thus, the HCV 5′ untranslated region (UTR) is now recognized as comprising 349 nucleotides, although it is possible to speculate that these additional nucleotides are part of a second, as yet undetected, stem–loop at the extreme 5′ terminus of the genome.
Response to interferon therapy: influence of human leucocyte antigen alleles in patients with chronic hepatitis C
Authors: Sim H. , Wojcik J. , Margulies M. , Wade J. A. , Heathcote J.
Published: March 2003

The response to interferon (IFN) therapy in patients with chronic hepatitis C is characterized by normalization of the serum alanine aminotransferase (ALT) activity during treatment, but relapse within 6 months of cessation of therapy is common. Viral characteristics, such as the genotype and viral load, may influence the patient response to IFN. The aim of this study was to examine host factors, namely the genetically determined human leucocyte antigen (HLA) class II alleles, in patients with chronic hepatitis C, and their relationship to the response to IFN therapy. Seventy white patients with chronic hepatitis C, treated with IFN‐α for 6 months, were enrolled in the study. Serum ALT was measured at the end of treatment to assess short‐term response and again 6 months post‐treatment to assess sustained response. Sequence‐specific primers were used in the polymerase chain reaction (PCR) to amplify genomic DNA isolated from peripheral mononuclear cells. HLA class II alleles were determined by analysis of the amplicon by gel electrophoresis and hybridization of sequence‐specific oligonucleotide probes. At the end of treatment, 25 of the 70 patients (36%) had a normal ALT. By 6 months post‐treatment, only six patients (9%) had a sustained normalization of ALT. The frequency of the allele DRB1*0404 was significantly higher in patients with a sustained response as compared to those lacking such a response (25.0%vs 2.3%, with a Bonferonni‐corrected P‐value of 0.019). There was no difference in the frequency of other class II alleles at the DRB1 and DQB1 loci in responders as compared with non‐responders. Therefore, we conclude that the maintenance of a response to IFN in chronic hepatitis C may be, in part, determined by genetic factors in the host.