bluuebunny/crossref_metadata_2025 huggingface dataset:
Treating a Dog Phobia in a Person with Down's Syndrome by Use of Systematic Desensitisation and Modelling
Authors: Freeman Susan
Published: August 2009

This case study is of a 31‐year‐old gentleman who has Down's syndrome and a dog phobia. The study shows how the use of systematic desensitisation alongside modelling reduced the client's anxiety levels when presented with feared stimulus and how access to the community increased during treatment.
Teaching Psychological Strategies for Managing Auditory Hallucinations
Authors: Leggett Janice , Hum Catherine , Goodman Wendy
Published: August 2009

In recent years cognitive‐behavioural techniques have begun to be applied to psychotic symptoms with positive results. There is little in the literature to suggest that such techniques have been used to help people with learning disabilities who experience psychosis. The case report provided here details the teaching of cognitive‐behavioural strategies for managing auditory hallucinations and their effective use by a woman with mild learning disabilities. A number of benefits of the intervention are noted including decreases in subjective distress and use of PRN medication, as well as improved mood and reported increases in the use of positive coping strategies and self‐esteem.
‘Born to …’— Genetics and Behaviour
Authors: Berney T. P.
Published: August 2009

In its ascendancy, the study of human genetics is shifting from the inheritance of physical structure to that of behaviour and personality; seeking the secret machinery which joins the inherited code to the quirk of character. At the start of the century human behaviour was thought to be largely learned and to stem from upbringing, the blank slate of personality being moulded by parents and events. What had been learned could be unlearned and this accorded with the idea of free will expressed in Cassius' claim that ‘the fault, dear Brutus, is not in our stars, but in ourselves, that we are underlings’. Now, at the century's close, the influence of breeding is back in fashion, bringing the implacable effects of genetic determinism and bad blood. The implications for the successes and failings of the ‘normal’ population are far‐reaching. In learning disability, many of these ideas are contained in the concept of the ‘behavioural phenotype’.
‘Whatever's on her Plate’: Food in the Lives of People with Learning Disabilities
Authors: Rodgers Jackie
Published: August 2009

Healthy eating has been identified as a particular issue for people with learning disabilities (Department of Health, 1995). This is not simply an issue to be considered in the light of the eating patterns of any individual. Health choices cannot be divorced from the social and economic circumstances in which people live. Neither is the relationship between food and health confined to its nutritional importance; food has a social and emotional significance. This paper reports the findings of a study that looked at a number of aspects of food in the lives of a group of 30 adults with learning disabilities. The paper reveals the less than healthy eating patterns of the study participants and their limited opportunities to influence what they ate. It describes participants' knowledge of healthy eating, and the difficulties people had in obtaining easy to understand information. Finally, strategies that take into account the preceding discussions, and which support people towards healthy eating, are suggested.
Physical Activity, Exercise and Health of Adults with Mild and Moderate Learning Disabilities
Authors: Messent Peter R. , Cooke Carlton B. , Long Jonathon
Published: August 2009

The aim of the study was to evaluate the cardiorespiratory fitness, levels of obesity, daily levels of physical activity and barriers to a physically active lifestyle in a group of 24 adults with mild and moderate learning disabilities (aged 23–47 years, mean age 34). The efficacy of two community‐based exercise intervention programmes for the group was also evaluated. The results showed that overall 50% of the men and 70% of the women were overweight, of whom 57% of the men and 100% of the women were obese. Mean cardiorespiratory fitness levels were 20% to 28% lower for the men and 42% lower for the women compared with average values for the general population. Physical activity profiles indicated that 22 of the participants were below recognised minimum levels of physical activity. Barriers to physical activity specific to the learning disability population included transport needs, staffing ratios, financial resources and unclear policy guidelines for day and residential service provision.
The All Wales Strategy, Self‐Advocacy and Participation
Authors: Whittell Bridget , Ramcharan Paul
Published: August 2009

The All Wales Strategy for the Development of Services for Mentally Handicapped People (Welsh Office, 1983) stated that representatives of people with learning disabilities be involved in the planning, management and review of services. Using data from an all Wales survey of self‐advocacy groups carried out in 1994 it is argued in this paper that participation from the self‐advocacy movement in service planning forums has only been partially successful. The difficulties of fostering meaningful participation relate to practical issues such as making meetings more accessible and providing support. They also relate to maintaining the independence of groups, to funding, and to wider, non‐service related roles people with learning disabilities might have in their communities. Some of the implications for the self‐advocacy movement are discussed.
Using Specific Approaches for Individual Problems in the Management of Anger and Aggression
Authors: Lindsay William R. , Overend Helen , Allan Ronald , Williams Christina , Black Laura
Published: August 2009

This paper investigates treatment for anger and aggression using a variety of methods. Assessments include direct observation, self‐recording of frequency of aggressive incidents, self‐recording of feelings of aggression, provocation role‐plays, and provocation inventories. Treatment approaches include two forms of relaxation (BRT and APR), discussions and exercises on the understanding of emotion, role‐plays to develop skills for dealing with feelings of anger, and exercises in the way in which individuals construe various situations. Three participants illustrate how these assessment and treatment methods can be used to tailor treatment to suit the particular problems displayed by individuals. The reasons for choosing particular methods are discussed as are the ways in which individuals respond to the programmes of therapy.
Assessment and Treatment of Self‐injury with a Man with a Profound Learning Disability
Authors: Carson Gerry , Clare Isabel C. H. , Murphy Glynis H.
Published: August 2009

Despite developments in the research literature on the functional analysis of self‐injury, relatively few accounts are available of its application to clinical practice with adults living in ordinary health or social care settings. We describe work with a man with a profound learning disability, very limited skills, and chronic self‐injurious behaviour, living in a barren long‐stay hospital. Functional analysis identified physical discomfort, lack of sensory stimulation, and social/physical isolation as factors contributing to his self‐injury. Based on LaVigna et al.'s (1989) organisational framework, a package of non‐aversive interventions was introduced. The service‐user's self‐injury decreased markedly. However, this improvement was not maintained after he moved to ‘mainstream’ community‐based social care where, unexpectedly, there were fewer opportunities for participation in purposeful activities. The outcome illustrates the importance of competent social care provision in supporting any benefits gained through intensive assessment and treatment.
A Cognitive‐Behavioural Intervention to Address Inappropriate Masturbation in a Boy with Mild Learning Disabilities
Authors: Withers Paul S. , Gaskell Sarah L.
Published: August 2009

A minimally aversive cognitive‐behavioural intervention was found to eliminate the inappropriate masturbation of an 11‐year‐old boy with mild learning disabilities. Intervention strategies included discussion and education surrounding appropriate masturbatory behaviour, imagery and distraction techniques and positive reinforcement via parental involvement. Improvements were maintained at one‐month and 12‐month follow‐ups. The discussion focuses on a number of ethical issues raised by this intervention.
Assessing and Intervening in the Communication Environment
Authors: Bradshaw Jill
Published: August 2009

An approach to implementing a total communication environment with a man who has severe learning disabilities, a profound hearing loss and challenging behaviour is described. This involved teaching the staff team visual modes of communication and supporting staff to use these methods. The intervention was evaluated by conducting observations of the communication acts taking place prior to and one year after the intervention.

Improvements were found in the amount of communication acts which were accompanied by signs and the range of communication functions employed. Changes were also reported in the communication skills set of the person with learning disabilities. Staff's perception altered from seeing him as someone who was challenging, to someone who was challenged by his hearing loss and communication difficulties.
Anger Management Training and People with Moderate to Severe Learning Disabilities
Authors: Rossiter Rowena , Hunnisett Emma , Pulsford Mandy
Published: August 2009

This paper outlines an Anger Management Programme specifically tailored for people with moderate to severe learning disabilities using the principles of Cognitive Behavioural Therapy in a group setting. The metaphor of a Traffic Light was used in which each light represents a different stage in the process of Anger Management: relaxation, self‐instructional training and problem solving. Within the framework of an individualised Anger Management Traffic Light System, participants engaged in role‐play with video feedback to develop an understanding of their own reactions to anger‐arousing situations and learn new skills to manage their anger. This small, time‐limited group seemed successful in demonstrating that people with moderate to severe learning disabilities are able to make use of a simplified Cognitive Behavioural approach to Anger Management, to monitor and modify their own thoughts and behaviour. Most progress took place where participants had a consistent, caring, high quality living environment, with carers committed to systematic support and follow‐up.
The Five Accomplishments: A Framework for Obtaining Customer Feedback in a Health Service Community Learning Disability Team
Authors: Murray George C. , McKenzie Karen , Kidd Gillian R. , Psychologist Shradha LakhaniAssistant , Sinclair Bridget
Published: August 2009

This paper examines the usefulness of using the philosophy of normalisation and, in particular, O'Brien's (1992) Five Accomplishments as a basis for evaluating client satisfaction with a community‐based health service learning disabilities team. It is based on a survey of a group of people with mild learning disabilities, using the Five Accomplishments as a framework for a semi‐structured interview. Areas of client satisfaction and dissatisfaction are discussed in the context of the use of a value‐based means of obtaining feedback from clients. Limitations of interviewing techniques and specifically those used in this study are reviewed.
The Use of Natural Therapeutic Holding as a Non‐aversive Physical Intervention in the Management of Violence
Authors: Stirling Christopher
Published: August 2009

Whilst is is currently recognised and acknowledged that the use of physical interventions in the management of aggression and violence is appropriate in some circumstances, the aims, values and application of such approaches have come under closer scrutiny in recent years. It is now accepted that any physical intervention must be non‐aversive in application and be considered as part of an overall programme which emphasises the development of positive alternative behaviours other than violence. Developments in risk management have placed a great onus on professionals to develop specific intervention programmes which not only consider the risks presented by the client, but also consider the risks associated with the interventions used. Natural Therapeutic Holding (NTH) addresses these issues and provides not only some answers to the professional, legal and ethical debates, but also equips carers with a set of interactive and responsive skills which can be used therapeutically.
Bed Blockage in an Acute Admission Service for People with a Learning Disability
Authors: Cumella Stuart , Marston Geoffrey , Roy Ashok
Published: August 2009

Previous research has observed an accumulation of in‐patients in admission facilities for people with a learning disability. This study looks at a sample of 21 patients who had been admitted for more than three months in admission facilities managed by an NHS Trust, and identifies diagnosis, circumstances leading to admission, and discharge planning. Almost all were appropriate for discharge, but could not be discharged because of lack of appropriate non‐hospital facilities for people with a learning disability and a severe psychiatric disorder or behaviour problem. It is recommended that health and social services commissioners jointly invest in community‐based services and skilled staff to reduce the inappropriate use of hospital beds.
Doing Research with Lonely People
Authors: Booth Wendy
Published: August 2009

Eleven years ago Wendy Booth was involved in a research study that looked at the effects of relocating people with learning difficulties from long‐stay institutions into less restrictive accommodation. She became friends with one of the women who was moving from hospital and they still see each other often. Two subsequent research studies have also left a legacy of people who phone or write to her on a regular basis. This paper addresses the ethical implications of including lonely people as partners in research.
The Gerry Simon Lecture, 1998: Enhancing the Quality of Life of People Receiving Residential Support
Authors: Felce David
Published: August 2009

Now that hospital resettlement has almost been completed, it is time to take stock of the quality of the alternative residential services provided. The original idea of creating a comprehensive local pattern of provision so that people could leave the family home during early adulthood and enjoy a typical ‘ordinary life’ had implications for (1) the scope of provision, (2) its nature, (3) the status and role of the person being supported, and (4) the quality of opportunity and support offered. The current state of each of these will be considered and recommendations made.
An Examination of the Importance of Aspects of Services to People with a Learning Disability
Authors: McKenzie Karen , Murray George C. , Matheson Edith
Published: August 2009

The present study examined the importance of some aspects of services received by individuals with a learning disability. All of the items were rated as important by over 85% of respondents. Only two significant differences were found among the participants in relation to (a) length of hospitalisation and (b) degree of learning disability, suggesting a consensus view. The relevance of evaluating the importance of aspects of service provision in relation to consumer satisfaction and quality of life research is discussed.
Genetic Counselling: A Consideration of the Potential and Key Obstacles to Assisting Parents Adapt to a Child with Learning Disabilities
Authors: Barr Owen
Published: August 2009

The provision of genetic counselling is now a key strategy aiming to reduce the number of children born with learning and other disabilities. Most professionals have some understanding of the possible genetic origins of learning disabilities and the majority will come in contact with parents who have received genetic counselling. However, despite these apparent familiarities within the subject area, many health, social care and education professionals with learning disability services do not appear to reflect on the wider issues associated with the possible mixed consequences of genetic counselling. The wider impact of receiving personal genetic information needs to be appreciated by all professionals involved in providing support to families of children with learning disabilities. In particular, how this may assist or hinder parents and other family members adapt to the presence of learning disabilities in a child. This paper considers the reported advantages and limitations of genetic counselling as a key strategy in the reduction of the genetic causes of learning disabilities in children. It also outlines some practical and research steps that could be taken to further enhance the contribution of genetic counselling in services for people with learning disabilities.
Researching Together
Authors: Williams Val
Published: August 2009

To be empowering, the research must be designed with a group of people who have decided to obtain power, and then must be conducted so that the group learns how to do the research as well as decides what research needs to be conducted. (Sample, 1996: 320)

This article describes a project in which Bristol Self Advocacy Group members visited similar groups in their area, and carried out group interviews based on their own research questions. Some academic researchers appear to question the genuine research involvement of people with learning difficulties and I attempt to answer some of these views. The group has already published, in their own names, their views about the process of doing research and their findings (Palmer & Turner, 1998; Palmer et al., in press), and have produced a booklet aimed at other self advocacy groups (Finding Out, 1999). However, in view of the importance of such a group expressing their own viewpoint directly, a word of explanation is in order about the authorship of the present article. It arose originally from my attempts to summarise for the Research Group some of the literature mentioned in this paper, which resulted in an ‘alternative paragraph’ article, in which I wrote one point, and one group member responded in the next paragraph. That project is still in progress, but in the meantime, the group members wanted me to write the present article. I include their own words and writings at several points, but this remains essentially my account of what has happened.
Community Care for People with Learning Disabilities: Specialist Learning Disabilities Health Services Following Resettlement
Authors: Bailey Nicola M. , Cooper Sally‐Ann
Published: August 2009

Health services for people with learning disabilities have changed considerably in the recent past, with the resettlement of individuals from institutions and a focus on community care. However, there is little available information on national averages of specialist learning disabilities health service provision in National Health Service (NHS) Trusts which have completed their resettlement programmes. A survey of specialist health services to people with learning disabilities was undertaken by means of two postal questionnaires to NHS Trusts in England and Wales which provide learning disabilities services. Thirty NHS Trusts had completed their resettlement programmes and their specialist learning disabilities services were analysed in detail and comparisons made with the NHS Trusts which still retained placements in an institution. These comparisons showed that NHS Trusts which had completed the resettlement process had significantly fewer long‐stay placements and employed significantly fewer learning disabilities psychiatrists than did other NHS Trusts. However, similar numbers of other learning disabilities health professionals were employed by the two groups of NHS Trusts to work with people with learning disabilities in the community. This suggests that when institutions close, the development of community health services has not been accompanied by the increase in resources that one might have expected.
Psychosocial Aspects of the Management of Epilepsy in People who have Learning Disabilities
Authors: Hawkins Emma , Shillitoe Richard
Published: August 2009

Learning disabilities and epilepsy often occur together. Each in its own right and in association with the other can present significant management challenges. Many of these challenges are psychological, social or educational in nature. They require a detailed assessment and regular review and monitoring. Some of the difficulties that will be encountered are communication problems, which can make accurate assessment and formulation difficult. Behavioural problems which are easily mis‐attributed to one or other of the conditions are also common. Effective management will require a close collaboration between carers, the primary care team and specialist services, amongst whom knowledge and information must be exchanged. When balancing the need for seizure control with a patient's need for quality of life, it must not be assumed that the health professionals' views will necessarily be the same as those of the patient or the patient's family. Two case histories which illustrate these problems are presented.
What Choice: A Consideration of the Level of Opportunity for People with Mild and Moderate Learning Disabilities to Lead a Physically Active Healthy Lifestyle
Authors: Messent Peter R. , Cooke Carlton B. , Long Jonathan
Published: August 2009

This paper addresses two questions. Firstly, do inequalities of opportunity exist between the general population and adults with mild and moderate learning disabilities to lead a physically active lifestyle? Secondly, should the provision of equivalent opportunities be considered a human right? For the learning disability population the right to opportunities to be physically active can be divided into primary and secondary rights, the former is the right to opportunities, the latter is whether and how the opportunities are taken up. The principle of distributive justice gives people with a learning disability the same right as others to be physically active. Realisation of such a right would bring the potential for tangible health benefits. This review suggests that care in the community is insufficiently resourced to provide adequately beyond basic needs and that significant inequalities do exist between the general and learning disability populations in relations to opportunities and choices to be physically active.
The Changing Role of Parents' Organisations
Authors: Beail Nigel
Published: August 2009

This paper provides a descriptive account of the role of a local voluntary parents' organisation over a 50‐year period. Information was obtained from parent members and from first‐hand involvement in this process. The report serves to illustrate the changing role of parents in developing, improving and providing services for people with learning disabilities and considers issues for the future.
Using Staff Consultation to Facilitate the Emotional Development of Adults with Learning Disabilities
Authors: Arthur Andrew R.
Published: August 2009

The emotional development and emotional difficulties of people with learning disabilities is a much‐neglected area of service provision. Attempts to understand and treat the emotional‐developmental needs and problems of this population are reviewed. Whilst there is some evidence that psychotherapeutic methods have been successfully applied, it is unlikely there will ever be enough psychotherapists to provide adequate individual treatment. This article proposes one response to the problem by demonstrating how the process of consultation can enable care‐staff to develop an understanding response to this area of their clients' lives. A model of consultation (process consultation) that is relevant to the development of care‐staff's therapeutic skills is described.
Bereavement Counselling and Support for People with a Learning Disability: Identifying Issues and Exploring Possibilities
Authors: Read Sue , Frost Irene , Messenger Neil , Oates Sylvia
Published: August 2009

Counselling and support for bereaved people who have a learning disability has historically been a neglected area, for many reasons. A voluntary organisation which positively embraced the challenges of working with a somewhat ‘different’ client group (people with learning disabilities) from a bereavement counselling perspective is offered as an example of positive practice. As other voluntary bereavement counselling organisations may seek to offer such bereaved individuals the counselling and support that they may require in the future, the role and function of the bereavement counsellor is identified and clarified and the characteristics of such organisations explored. Case illustrations are offered in an effort to help the reader to engage with the nature of the work undertaken, and the challenges involved.
Speaking up for Yourself: Description and Evaluation of an Assertiveness Training Group for People with Learning Disabilities
Authors: Weston Clive
Published: August 2009

Current service philosophies place emphasis on service users making choices for themselves and on acquiring the maximum possible degree of independence. Partly in response to this, practitioners have attempted to help service users develop skills of assertiveness. However, there are relatively few published accounts of assertiveness training for people with learning disabilities, and even fewer which attempt to evaluate the effectiveness of training over a sufficiently long time period. This paper describes such a group for nine people with learning disabilities, and it includes a range of outcome measures at intervals up to 16 months from the first session. Difficulties in developing and administering suitable self‐report measures are discussed. Modest increases in assertive behaviour are reported for the majority of participants. The importance of seeing assertiveness training in the wider context of service user empowerment is emphasised.
Using Social and Educational Approaches to Enable a Man with Learning Disabilities to Develop his Sexual Identity and Orientation
Authors: Edmonds Carl , Collins Anthony
Published: August 2009

This paper describes the obstacles encountered by a young, gay man with a mild learning disability. His referral for ‘challenging behaviour’ to the Personal Relationships and Sex Education Team initiated a one‐to‐one sex education programme. When the work had been completed his frustration grew as he could not apply his learning and he desperately wanted a sexual partner. The work took a new direction to find a gay befriender to assist our client to access his community and continue his learning. This case study highlights the need for carers and professionals to assist people with learning disabilities to break down the barriers of community resistance that prevents them from integrating and developing their chosen sexual identity.
Group Work with Women with Learning Disabilities
Authors: Dorney Margaret
Published: August 2009

The intention of this paper is to give an insight into the way in which group work offers women with learning disabilities the opportunity to (a) see what they have in common with other women and (b) enable them to develop a positive sense of themselves and their sexuality. The paper contains a summary of the author's role and the context in which this group work takes place. Descriptions of group recruitment, referral process, group criteria, group work practice and methods are offered. The key themes which women with learning disabilities consistently raise within the groups are explored and examples are given to illustrate how the women's group responds to these. The paper concludes by listing some of the important factors which facilitators need to be mindful of when setting up groups for women with learning disabilities.
Development of the FOCUS (Focus on the Outcomes of Communication Under Six), a communication outcome measure for preschool children
Authors: THOMAS‐STONELL NANCY L , ODDSON BRUCE , ROBERTSON BERNADETTE , ROSENBAUM PETER L
Published: August 2009

Aim  Our aim was to develop an outcome measure, called Focus on the Outcomes of Communication Under Six (FOCUS), that captures real‐world changes in preschool children’s communication. Conceptually grounded in the World Health Organization International Classification of Functioning, Disability and Health framework, the FOCUS items were derived from observations of change provided by parents and clinicians after speech–language therapy.

Method  Participating families (n=165) were drawn from a convenience sample at partner institutions in Ontario, Newfoundland and Labrador, and Nova Scotia. All children had speech, language comprehension, and/or language production disorders and were receiving speech–language therapy. The age of the children ranged from 1 year 2 months to 5 years 6 months (mean=3.8y; SD=0.91y), and 119 children were male. Three test phases were completed. The measure was revised according to item analysis and parent/clinician feedback after phase 1 (n=74) and phase 2 (n=65). In phase 3 (n=26), the Pediatric Quality of Life Inventory (PedsQL), a health‐related quality of life measure, was added to establish construct validity.

Results  In phase 1, item analysis revealed high internal consistency for both parents (Cronbach’s α=0.87) and clinicians (Cronbach α=0.97). These values indicated redundancy, so 31 items were cut. Five items for young children were added. In phase 2, internal consistency remained high for both parents (Cronbach α=0.98) and clinicians (Cronbach α=0.83), indicating redundancy of items. Twenty‐seven items were removed. In phase 3, parents and clinicians reliably scored the FOCUS in 10 minutes. They stated that it provided an accurate snapshot of the child’s communication. Internal consistency for parents remained high (Cronbach α=0.96). Children with higher FOCUS scores at the end of treatment had higher PedsQL total scores (r=0.466, p=0.029).

Interpretation  The FOCUS is a usable measure of a child’s ability to communicate and participate in his or her community. It demonstrates high internal consistency and construct validity.
Biomedical and health informatics in Peru: significance for public health
Authors: Curioso Walter H. , Peinado Jesus , Rubio Crisogono F. , Lazo‐Escalante Marcela , Castagnetto Jesus M.
Published: August 2009

Introduction

This issue of the feature column reports on developments in Peru on the use of information and communication technologies to improve public health. The authors describe how cell phones and hand‐held devices are being deployed to monitor diseases. Recent concerns about the spread of swine flu highlight the importance of robust public health systems in developing countries.1

Jeannete Murphy

Reference

1.
British Journal of Healthcare Computing and Information Management, 30 April 2009. http://www.bjhcim.co.uk/news/2009/n904046.htm (accessed 18/05/09).
CHARACTERISATION OF THE ALPHA‐ADRENOCEPTORS OF THE RAT RENAL VASCULAR BED*
Authors: SCHMIDT M. , KRIEGER J.‐P. , GIESEN‐CROUSE E. , IMBS J.‐L.
Published: August 2009

Summary— Postjunctional renal alpha‐adrenoceptors were studied (1) in vivo, on the renal vasculature of the anaesthetized rat and compared with those in the femoral vasculature, and (2) in vitro, on the renal vascular bed of isolated perfused rat kidney.

In vivo, renal and iliac blood flows were measured with an electromagnetic flow meter. The i.v. injection of (‐)‐phenylephrine (1–16 μ/kg) and B‐HT 920 (0.6–600 μ/kg) induced an increase in both renal and iliac vascular resistance, inhibited respectively with prazosin (300 μ/kg) or yohimbine (300 μ/kg). In the kidney, maximum response to B‐HT 920 was equivalent to 64% of that to (‐)‐phenylephrine; on the iliac vasculature, vasoconstrictor responses to both drugs were identical, but only corresponded to 50% of the maximum renal response to (‐)‐phenylephrine. This indicates the predominance of alpha1‐over alpha2‐adrenoceptors in the renal vascular bed.

In vitro, on the isolated perfused rat kidney, vasoconstriction was induced by the preferential alpha1‐adrenoceptor agonists [(‐)‐phenylephrine, cirazoline and methoxamine] and the preferential alpha2‐adrenoceptor agonists (alpha‐methylnoradrenaline, dopamine and clonidine) at concentrations at which they lose their selectivity for the alpha2‐adrenoceptors; all responses were antagonised by prazosin but not by yohimbine. B‐HT 920, the selective alpha2‐adrenoceptor agonist, only induced renal vasoconstriction in vitro under concomitant infusion of rabbit plasma.
AGONIST/ANTAGONIST ACTIVITY OF ERGOCRISTINE AT ALPHA‐ADRENOCEPTORS IN THE RAT
Authors: ROQUEBERT J. , DEMICHEL P.
Published: August 2009

Summary—

The action of ergocristine at α‐adrenoceptors was studied in vivo in the pithed rat, and in vitro on the rat isolated vas deferens.

In the pithed rat, the pressor response to ergocristine was reduced competitively by yohimbine, but not by prazosin.

Ergocristine decreased the tachycardia elicited by electrical stimulation of the cardioaccelerator sympathetic nerves, this effect being antagonized by yohimbine.

At postsynaptic α1‐adrenoceptors, on the vas deferens of the rat, ergocristine antagonized the contraction induced by phenylephrine in a competitive manner (pA2 = 7.85).

These results show that vasoconstriction due to ergocristine is mediated by α2‐adrenoceptors and that, in the rat, ergocristine acts as an α2‐adrenoceptors agonist, and an α1‐adrenoceptors antagonist.
ARTERIAL AND VENOUS EFFECTS OF VERAPAMIL IN NORMAL VOLUNTEERS
Authors: THUILLEZ C. , DUHAZE P. , FOURNIER C. , LAPIERRE V. , GIUDICELLI J.‐F.
Published: August 2009

Summary—

The effects of verapamil (120 mg orally) and a placebo on arterial pressure, heart rate, PR interval, arterial flows and diameters of the brachial and carotid arteries (pulsed Doppler technique), forearm vascular resistance, and venous diameter and compliance (cutaneous microstrain gauge and plethysmography) have been compared over a 10‐hr period in six healthy volunteers during a double‐blind and cross‐over study.

Verapamil reduced diastolic blood pressure by approximately 10 mm Hg, did not affect heart rate and increased PR interval by approximately 15%.

Verapamil significantly increased brachial and carotid arterial blood flows by 56% (P<0.01) and 16% (P<0.05), respectively, but the diameters of these vessels were not significantly modified (+ 7 and + 4%, respectively, NS). Forearm vascular resistance decreased by 40% (P<0.01), indicating that verapamil preferentially dilates small arteries. All these effects peaked at 2 h after drug intake and lasted for 6 h.

Verapamil increased hand dorsal vein diameter and flow by 95% (P<0.05) and 80% (P<0.05), respectively, from 2 to 4 h after drug intake but venous compliance, assessed by the venous diameter/venous flow ratio, was not significantly modified (from 0.71 to 0.69, NS), thus indicating that veins are not directly affected by this drug.
RELATIONSHIP BETWEEN PLASMA MEXILETINE LEVELS AT STEADY‐STATE: PRESENCE OF VENTRICULAR ARRHYTHMIAS AND SIDE EFFECTS
Authors: PEYRIEUX J.C. , BOISSEL J.P. , LEIZOROVICZ A. ,   IMPACT Research Group
Published: August 2009

Summary— The relationships between plasma mexiletine levels and the presence of ventricular arrhythmias and side effects were studied on patients from IMPACT (International Mexiletine and Placebo Antiarrhythmic Coronary Trial). 630 patients who had suffered a myocardial infarction were randomized between placebo and mexiletine.

Plasma levels were measured 1 month after the beginning of treatment. Arrhythmia findings (presence or absence of premature ventricular contractions (PVCs), couplets, runs, bigeminy, trigeminy, multiformity and various combinations) were assessed from 24‐h ambulatory ECG recordings. The empirical logistic transform was used for modeling the relationships. For all these variables, except the presence of PVCs, trigeminy and runs, the association with plasma level was significant: the higher the plasma level, the lower the rate of occurrence of the particular arrhythmia. This was true whether or not the patient had the arrhythmia at baseline. Analyses based on the same model showed a significant correlation between plasma level and tremor, constipation, sexual problems and the presence of at least one side effect.

As the levels of mexiletine at which side effects become frequent are in the same range as those necessary to suppress arrhythmias, the therapeutic range is narrow and individual dose adjustment should preferably be made.
ATROPINE ENHANCES NEUROMUSCULAR TRANSMISSION IN HUMANS
Authors: WALI F.A. , BRADSHAW E.G. , SUER A.H. , DARK C.H.
Published: August 2009

Summary— The effect of atropine (1–10 μ‐kg‐1) on neuromuscular transmission in humans was studied by analysing its effects on the amplitude of indirectly‐elicited twitch (0.2 Hz) and tetanic (50 and 100 Hz for 1 s duration) contractions. Six patients, free from any neuromuscular disorders, undergoing orthopaedic surgery, were included in the present study. The patients received either no premedication or the oral benzodiazepine, temazepam, 30 mg 1–2 h pre‐operatively. Anaesthesia was induced with propofol (1–2 mg‐kg‐1, i.v., over 20 s). The patients breathed no less than 30% oxygen in nitrous oxide, halothane (1%) or enflurane (1–2%). Incremental doses of fentanyl (50–100 μ) were given to provide additional analgesia.

The ulnar nerve was stimulated, supramaximally, at the wrist, and control mechanical responses of the adductor pollicis muscle, to nerve stimulation at 50 and 100 Hz for 1 s duration, were recorded. Theses responses were repeated at 2, 5 and 10 min intervals, after injection of atropine (1–10 μ‐kg‐1). At the same time, heart rate and blood pressures (systolic and diastolic) were recorded.

The results showed that atropine enhanced the tetanic contractions, elicited at 50 and 100 Hz for 1 s duration, by 27 ± 1.2% (50 Hz and atropine, control 220 ± 13 g tension), and by 43 ± 7% (100 Hz and atropine, control 333 ± 26 g tension) at the 5 min intervals (mean ± S.E., n = 6). The heart rate and blood pressures were also increased, by 24 ± 2.5% (heart rate control 110±3.5 beats/min), 16±1.0% (systolic control 138±2.2 mm Hg), and 13±1.1% (diastolic control 76±1.5 mm Hg), and this precluded the use of higher doses of atropine (e.g. 1.2 mg, i.e. 20 μ‐kg‐1) in our study.

The results and mechanism of action of atropine, at the neuromuscular junction, are discussed with reference to animal work, in which atropine has been shown to enhance neuromuscular transmission and/or transmitter (ACh) release, possibly by acting on muscarinic presynaptic inhibitory receptors, which are involved in the feedback mechanism of transmitter release.
EFFECT OF PEPTIDYL‐DIPEPTIDASE INHIBITORS IN EXPERIMENTAL CONVULSIONS IN MICE
Authors: MIÑANO F.J. , SERRANO J.S. , SANCIBRIÁN M. , SERRANO M.I.
Published: August 2009

Summary— The anticonvulsant effect of compounds that inhibit peptidyl‐dipeptidase (PDP) on bicuculline (BIC)‐ and strychnine (STRYC)‐induced seizures was assessed after intracerebroventricular (ICV) or intraperitoneal (IP) administration in Swiss albino mice. STRYC‐induced seizures were delayed by ICV injections and high IP doses of captopril, but not by ICV or IP injections of enalapril or by lower doses of captopril (0.1 mg/kg and 1 mg/kg IP). BIC‐induced seizures were not suppressed by ICV or IP injections of either compound; on the contrary, captopril and enalapril exhibited proconvulsant effects when given IP or ICV by shortening the time of onset of tonic seizures and death. Results indicate that the anticonvulsant effect of captopril against STRYC‐induced seizures is not mediated by central γ‐aminobutyric acid (GABA) receptors or by the inhibition of PDP.
CHANGES IN PLATELET FREE Ca2+CONCENTRATION AFTER CHRONIC DIGOXIN TREATMENT
Authors: QUAN‐SANG K.H. LE , DAVID‐DUFILHO M. , KERTH P. , PERNOLLET M.G. , FRISK‐HOLMBERT M. , MEYER P. , DEVYNCK M.A.
Published: August 2009

Summary—Cell Na+ and Ca2+concentrations control each other by various mechanisms. In excitable cells from various origins, Ca2+extrusion from the cell and its entry are dependent for a large part on the activity of the Na+, Ca2+‐countertransport system. Cytosolic free Ca2+concentration is also controlled by the Na+–H+ exchange activity. To analyze the changes in cytosolic Ca2+concentration accompanying the reduction of the membrane Na+ gradient, cytosolic free Ca2+concentration ([Ca2+]i) was measured by fluorescent dyes in platelets and erythrocytes from healthy subjects, before and during digoxin treatment (0.25 mg/day for 6 days). [Ca2+]iwas increased in platelets from 169±30 to 321±61 nmol/l (n= 7,P<0.02) and unchanged in erythrocytes (121±6 and 104±7 nmol/l). This increase in platelet [Ca2+]iwas not accompanied by a change in serotonin content (5.43±0.67vs5.49±0.61 10−7mol per 1011cells) and could not be reproduced byin vitroaddition of 10−4mol/l ouabain (198±33vs186±73 nmol/l). The enhanced [Ca2+]iin platelets is thus not a short‐term consequence of a reduced membrane Na+ gradient, but reflects either the overload of intracellular Ca2+stores or an enhancedin vivostimulation by hormones or neurotransmitters.
COMPARATIVE EFFECTS OF ZOPICLONE, TRIAZOLAM AND PLACEBO ON MEMORY AND PSYCHOMOTOR PERFORMANCE IN HEALTHY VOLUNTEERS
Authors: WAROT D. , BENSIMON G. , DANJOU Ph. , PUECH A.J.
Published: August 2009

Summary— This study evaluated the effects of acute doses of zopiclone (7.5 mg), triazolam (0.25 mg) and placebo on memory and psychomotor performance of 12 normal volunteers.

The subjects received both drugs in a repeated measure, double‐blind Latin square design. The tests (CFF, CRT, DSST, memory assessments) were performed before and 2 and 6 hr after treatment. Zopiclone and triazolam induced an anterograde amnesia affecting short‐term and long‐term memory which lasted less than 6 hr. No retrograde amnesia was observed. Two hr after drug intake of both hypnotics psychomotor performances were significantly altered compared with placebo. The subjects also felt more drowsy, dizzy, clumsy and tired, and less alert and energetic 2 hr after zopiclone and triazolam compared to placebo. There was no difference between the effects of the two hypnotics at the doses studied.
ANTIHYPERTENSIVE EFFECTS OF MESULERGINE: FURTHER EVIDENCE FOR A PERIPHERAL SITE OF ACTION OF DOPAMINE AGONISTS
Authors: BEGAUD B. , TRAN L. DANG , MONTASTRUC J.L. , MONTASTRUC P.
Published: August 2009

Summary—The cardiovascular effects of mesulergine were studied in anesthetized dogs. Intravenous (IV) administration (0.3 mg/kg) significantly decreased blood pressure in neurogenic hypertensive dogs without any change in heart rate. This effect was completely antagonized by IV administration of domperidone (0.5 mg/kg). Intracisternal administration of mesulergine (0.03, 0.3 and 3 mg/kg) did not produce any change in blood pressure. However, with the highest dose we observed a significant rise in heart rate during the first 2 min (which was probably nonspecific). These results suggest that mesulergine lowers blood pressure in sinoaortic‐denervated dogs by means of a peripheral mechanism probably involving DA2receptors. The findings confirm the potential interest of dopamine‐receptor agonists as future antihypertensive agents.
QUANTITATIVE AUTORADIOGRAPHIC DETERMINATION OF BINDING SITES FOR A PERIPHERAL BENZODIAZEPINE LIGAND ([3H]PK 11195) IN HUMAN IRIS
Authors: VALTIER D. , MALGOURIS C. , GILBERT J.‐C. , GUICHENEY P. , UZAN A. , GUEREMY C. , Le FUR G. , SARAUX H. , MEYER P.
Published: August 2009

Summary— Specific binding sites of peripheral‐type benzodiazepines were investigated in human iris/ciliary body (8 eyes). Examination of color‐coded prints and densitometric quantification of autoradiograms were performed on slides (20 μm) labelled with [3H]PK 11195 (1 nM) at 25°C. Nonspecific binding was determined with PK 11211 (5 μM) or Ro 5–4864 (5 μM). Binding sites were present on all the slides, with equivalent density in the 3 regions of the preparation (ciliary body, iris, and pupil margin). The numbers of binding sites in ciliary body, iris, and pupil margin, respectively, were: 42.7 ± 0.2, 30.1 ± 0.5, and 37.4 ± 0.4 femtomol/mg protein. Labelling on the pupil margin seemed to coincide with the iris sphincter muscle.

The presence of peripheral benzodiazepine binding sites in iris muscular tissue, and particularly in the pupil margin, suggests that the iris preparation may be a valuable tool to detect putative physiological effects of peripheral benzodiazepines on muscular motility.
PHARMACOKINETICS OF HIGH‐DOSE IV ALIZAPRIDE IN PREVENTION OF CISPLATIN‐INDUCED EMESIS
Authors: CANAL P. , ROCHE H. , PASQUIER M. , BUGAT R. , BERG D. , SOULA G. , CARTON M.
Published: August 2009

Summary— Alizapride is a new antidopaminergic‐related benzamide with specific antiemetic properties. Pharmacokinetics at a high repetitive dose (16 mg/kg) shows a biexponential plasma decay with T1/2α of 8.33 ± 2.47 min and T1/2β 2.8 ± 0.7 hr. Large Vdss and high total body clearance are apparent. We demonstrate an increase in drug exposure during the first 6 hr after CDDP infusion by shortening the interval between injections. We conclude that the rate of infusion of alizapride could be important in the efficacy of the drug.
CONVERSION FROM INTRAVENOUS TO ORAL SLOW‐RELEASE DISOPYRAMIDE IN ACUTE MYOCARDIAL INFARCTION
Authors: ZANNAD F. , ROYER‐MORROT M.J. , ZAKARI I. , SADOUL N. , ROYER R.J.
Published: August 2009

Summary— Twelve patients with acute myocardial infarction were given 1.5 mg/kg/5 min bolus + 0.4 mg/kg/hr 6 hr IV infusion of disopyramide followed by 250 mg twice daily of a slow‐release oral formulation of this drug.

Plasma concentrations of total disopyramide rapidly reached steady‐state within the therapeutic margins. The plasma steady‐state concentrations of the major metabolite mono‐N‐dealkyl‐disopyramide (MND) showed large intra‐individual variations. There was no correlation between plasma levels of either disopyramide or MND and the occurrence of anticholinergic side effects. The drug had no significant effect on mean blood pressure, heart rate, or ECG intervals.

This therapeutic regimen, including conversion from the IV form to oral slow‐release tablets, could be recommended in myocardial infarction.
EFFECTS OF PROGESTOGENS ON LIPEMIA AND LIPOLYSIS IN RAT: EFFECTS OF PROGESTERONE, MEGESTROL ACETATE, NORETHINDRONE ACETATE, AND NOMEGESTROL ACETATE
Authors: HAZARD M.‐C. , CLAVET M. , CHAPIGNAC A. , PARIS J.
Published: August 2009

Summary— Effects of 4 progestogens at equal dosages (5 mg/kg/day) on lipid metabolism and plasma glucose levels of adult female rats were compared. The 4 progestogens studied were progesterone (P) by SC injection, and megestrol acetate (MEG), norethindrone acetate (NOR), and nomegestrol acetate (NOM) PO.

MEG, a 17α‐hydroxyprogesterone derivative, induced significant increases in glucose, total and high‐density lipid (HDL) cholesterol, triglyceride, and phospholipid plasma levels. Treatment with NOR, a 19‐nortestosterone derivative, resulted in a reduced gain in body wt and in a marked decrease in all plasma lipid parameters. The 19‐norprogesterone derivative NOM, like P, did not alter lipid or glucose metabolism, despite a significant increase in body wt gain. In particular, no reduction in the HDL cholesterol level occurred. Plasma and tissue lipolytic activities remained unchanged.

The results of this study confirm interest in the therapeutic class of 19‐norprogesterone‐derived progestogens, exemplified by NOM, with respect to their lack of metabolic side effects.