bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards Outcome Measurements: Monitoring Effectiveness of Anger Management and Assertiveness Training in a Group Setting
Authors: Walker Tracy , Cheseldine Sally
Published: August 2009

It is becoming increasingly important for clinicians to justify the treatment approaches they use. This study illustrates one way of measuring therapeutic effectiveness in a small group of learning disabled individuals who frequently demonstrated aggressive or intimidating behaviours. The use of a self‐report measure, the Provocation Inventory (PI) to monitor change, can be easily implemented in everyday clinical practice. The PI allowed for responses to be categorised and consequently pre‐ and post intervention responses could be compared. Changes recorded using the PI were ambiguous in terms of ‘improvement’, although staff reports indicated group work to have been effective to some extent. The use of formal outcome measurements represents good clinical practice. Despite some limitations in the PI, some useful recommendations for its future use are documented.
The Introduction of Role‐play to a Group of Women with Learning Disabilities: Graded Stages in Developing Role‐play Skills and Some Practical Hints for Facilitating Role‐play
Authors: Allt Jackie , Fenner Susanne , Marvell Catherine
Published: August 2009

This paper describes the experiences of introducing role‐play in the context of a women's group aimed at developing assertiveness around appropriate and inappropriate touch. The aim of the group was to provide the women with skills they would be able to generalise to everyday situations. We aim to highlight an approach for overcoming the difficulties we have experienced in previous group work and give a practical guide for people attempting similar projects.
Communication Skills and Adults with Learning Disabilities: Eliminating Professional Myopia
Authors: van der Gaag Anna
Published: August 2009

There can be little doubt that effective communication is of crucial relevance to the quality of life of individuals with learning disabilities. What is much less certain is how ‘effective communication’ is defined, still less how it can be maximised. However, there has been considerable progress towards understanding the dual nature of communication difficulty; the intrinsic nature of an individual's communication and the extrinsic factors which influence communication experience in profound ways. This paper will discuss the development of communication skills in this context, outlining the essential components of a strategy for communication development. It will highlight the importance of a multidisciplinary approach to addressing the communication needs of adults with learning disabilities. It will stress the need for agreed standards and procedures, careful co‐ordination between health and social service agencies, and on‐going monitoring of service provision. Too often, too little has been provided on an ad hoc basis, with little concern for an overall strategy. Progressive services incorporate an agreed strategy on how to build communication skills for all services users, in the same way that strategies on housing or employment might be formulated. Communication development can only succeed on this basis.
Still at Home: Participation in Paid Employment of Mothers of Children with Learning Disabilities
Authors: Shearn Julia
Published: August 2009

The growing numbers of mothers in the work‐force reflects the importance that paid employment now has in the lives of most women. This paper presents findings from a study exploring the employment situation and aspirations of mothers of children with learning disabilities. The findings suggest that being a mother of a child with learning disabilities has a significant and enduring impact on employment for these mothers. However, the majority of non‐working mothers of children with learning disabilities wanted to work. It is argued here that the employment of mothers of children with learning disabilities should be a more explicit focus for policy makers, researchers and service providers.
Practising Partnership: Involving People with Learning Difficulties in Research
Authors: Ward Linda , Simons Ken
Published: August 2009

Traditionally, research has been done on people with learning difficulties, rather than with them. However, attitudes to this issue are changing. On the one hand some people with learning difficulties are seeking more active involvement, while on the other both researchers and funding bodies are exploring ways to involve people more widely within the research process. This article gives examples of people with learning difficulties helping to set the research agenda; advising and assisting with research projects; undertaking research themselves; and being both the target of, and actively involved in, the dissemination of research. It concentrates on describing practical examples of involvement rather than the theoretical context and debates surrounding it.
Ethical Dilemmas in Historical Research with People with Learning Difficulties
Authors: Rolph S.
Published: August 2009

This paper discusses the ethics of historical research with people with learning difficulties, and in particular those issues which arise in both oral and archival history. Pioneers in the work of collecting the life stories of people with learning difficulties debated some of the issues around biographical and autobiographical methods (Bogdan & Taylor, 1982). The history of learning disability has, however, until comparatively recently been a neglected subject. The histories that have existed have been written predominantly from an official viewpoint, have not included the views of people with learning difficulties themselves, and have tended therefore to be partial accounts (Kanner, 1964). A new development of the 1980s and 90s, however, has been the growing interest by people with learning difficulties in reclaiming their histories (Cooper, 1997; Barron, 1996; Lewis, 1997). Historians who have been supporting them have suddenly been faced with new ethical dilemmas which are only just beginning to be discussed in the literature (Potts & Fido, 1991; Atkinson et al., 1997; Rolph, 1998). In the following sections, I will highlight some of the issues which occur in this new historical research, and which particularly concerned me in my own research. I then discuss the methods adopted in an attempt to solve them.
Interviewing People with Learning Disabilities about Sensitive Topics: A Discussion of Ethical Issues
Authors: McCarthy Michelle
Published: August 2009

The discussion of ethical issues in this paper are set in the context of the author's PhD research, interviewing women with learning disabilities about their sexual experiences. The ethical concerns addressed include seeking informed consent, establishing confidentiality and anonymity, as well as reciprocity and identification between the researcher and researched. The paper argues for the development of clear principles of good practice.
‘Feeling Poorly’: Report of a Pilot Study Aimed to Increase the Ability of People with Learning Disabilities to Understand and Communicate About Physical Illness
Authors: Dodd Karen , Brunker Jo
Published: August 2009

There is a current emphasis from Department of Health publications on the need for people to take responsibility for monitoring and improving their own health. This includes people with a learning disability (PLD). This paper presents the findings of a pilot study which investigated whether people with learning disabilities can understand and communicate more effectively symptoms of illness. Assessments for GPs, clients and carers were designed in order to ascertain the nature of consultations currently taking place, and the level of awareness that clients had of their body and being ill.

From the assessment information gathered and reviews of the literature on primary health care access for PLD and children's experiences of pain, an appropriate teaching package was designed and a twice weekly group held for ten weeks. This aimed to teach body awareness and necessary skills for communicating with primary health care teams; and included the design, and implementation of a communication aid pack. Repeat assessments following the end of the group and after six months indicated that it is possible to teach people with learning disabilities to understand how their bodies function, to use pictures of pain to describe symptoms of illness and to understand more about the process of going to the doctors. This was facilitated by the use of communication aid resource which both doctors and clients evaluated as useful. For the information to be efficiently retained by the clients it is suggested that a greater degree of follow‐up work is undertaken on completion of the teaching group with participants, carers and GPs.
Developing an Alcohol Awareness Course for Clients with a Learning Disability
Authors: Forbat Liz
Published: August 2009

This paper details the pilot study of an Alcohol Awareness group, designed for the dissemination of information regarding the consumption of alcohol. Eight sessions focused on key issues such as units, myths surrounding alcohol, and techniques for refusing drinks. The pilot group comprised adults with learning disabilities resident in a Medium Secure Unit. Special emphasis is given throughout this paper to the user group to whom the intervention was aimed. An assessment tool was designed to measure the level of alcohol‐related knowledge which participants had prior to the course. The same assessment was administered to group members immediately following the course, and at a six‐month follow‐up. Increases in scores were evident for all participants in the post‐assessment. Discussion follows on the need for this addition to mainstream services. Issues of controlled drinking or total abstinence, and some suggestions for future interventions within the service, are also discussed. A package of information, handouts and session‐plans were developed throughout the course/and are available from the secure service on request.
An Integrated Communication and Exercise Programme in a Day Centre for Adults with Challenging Behaviours
Authors: Dobson Susan , Stanley Brian , Maley Lisa
Published: August 2009

It has been the tradition that communication programmes are perceived as discrete interventions set apart from mainstream day centre activities. The most common approach has been to link such communication programmes with some form of separate educational activities. However, this approach fails to reflect the fact that communication between staff and clients and the clients themselves naturally occurs all the time. Integration of communication programmes into ordinary daily routines across a variety of activities would therefore seem to be a better option. This requires close collaboration between staff who may have different professional backgrounds. This paper describes a small project which demonstrates that such a communication programme integrated within broader programmes of health care exercises can be a more efficient use of staff and client time. The social and communication skills which are learnt in natural settings promote staff and client well‐being and improve the client's functional use of communication.
Befriending: A Note of Caution
Authors: Hughes Andrea , Waldenm Sarah
Published: August 2009

‘Our relationships define who we are as individuals’ (Kennedy & Itkonen, 1993)

It is recognised that the quality and closeness of personal relationships underlie a fulfilled life. However, services for people with learning disabilities often find this aspect of human life the most difficult to promote. Recently, befriending schemes have represented one initiative designed to fill the gap. This paper follows the progress of one pilot project and its outcomes for four participants with learning disabilities. It is concluded that caution should be exercised in any similar scheme, and that careful monitoring should ensure that new relationships are not being formed at the expense of prior, possibly less transient ones.
Scaffolding the Story‐telling Abilities of a Group of Pupils with Learning Difficulties Using Computers: A Case Study
Authors: Turner Andrew
Published: August 2009

This paper reports the findings of a case study carried out in a special school catering for pupils with a wide range of learning difficulties. It looks at the way a group of Year 1 and 2 pupils responded to a series of teacher‐planned and conducted story‐telling sessions using pictures and a piece of commercially available software designed to provide a framework for story‐writing. The findings are discussed in relation to existing research on story‐telling by pupils with learning difficulties and to the concept of using Information and Communication Technology as a means of ‘scaffolding’ children's development in this area. Some wider issues relating to the development of the pupil's learning through story‐telling are discussed.
Considerations for Informing Safer Sex Education Work with Men with Learning Disabilities
Authors: Cambridge Paul
Published: August 2009

The sexuality of men with learning disabilities suggests that sexual health should be placed alongside consent to sex as a priority for sex education. This paper reviews HIV prevention and safer sex education work with men with learning disabilities, identifying considerations for responding to HIV in its third decade. While the effective targeting of HIV prevention remains with men with learning disabilities who have sex with men, new considerations are also emerging from experience with sex education, staff training and HIV prevention more widely, helping reshape and inform service responses and individual work.
Staff Attitudes Towards the Sexuality of Individuals with Learning Disabilities: A Service‐related Study of Organisational Policies
Authors: Murray James L. , MacDonald Raymond A. R. , Brown Gary , Levenson Victor L.
Published: August 2009

Numerous authors have discussed the need for empirical research concerning the sexuality of individuals with intellectual disabilities (Cambridge, 1997; Murray & Minnes, 1994). Within the present study, 332 employees from three different organisations (NHS, Social Services, and the private & voluntary sector) providing services to individuals with intellectual disabilities were invited to participate. Completed questionnaires were anonymously returned by 54% of the sample. Participants completed the 20‐item Sexuality and Intellectual Disabilities Attitude Inventory (SIDAI) (Murray et ah, 1995), and answered questions about their organisation's formal policies concerning client sexuality. In general, moderate to highly liberal attitudes towards client sexuality were reported by participants. More specifically, health‐care, management and professional staff reported significantly more liberal attitudes towards client sexuality than direct‐care staff. Significantly fewer NHS participants were familiar with the formal policies concerning client sexuality than participants from Social Services and the Private & Voluntary sector. Additional findings were that 56% of all participants indicated that these formal policies did not influence their interactions with clients. The results are discussed within the context of improved staff training. Organisations providing services to individuals with intellectual disabilities are encouraged to bridge the gap between policies and practice concerning client sexuality. Limitations and directions for future consideration are also discussed.
Low bone mass in patients with motor disability: prevalence and risk factors in 59 Finnish children
Authors: KILPINEN‐LOISA PÄIVI , PAASIO TAAVA , SOIVA MARTTI , RITANEN ULLA MAIJA , LAUTALA PENTTI , PALMU PETRI , PIHKO HELENA , MÄKITIE OUTI
Published: August 2009

Aim Children with motor disabilities are at increased risk of compromised bone health. This study evaluated prevalence and risk factors of low bone mass and fractures in these children.

Method This cross‐sectional cohort study evaluated bone health in 59 children (38 males, 21 females; median age 10y 11mo) with motor disability (Gross Motor Function Classification System levels II–V). Bone mineral density (BMD) in the lumbar spine was measured with dual‐energy X‐ray absorptiometry; BMD values were corrected for bone size (bone mineral apparent density [BMAD]) and skeletal maturity, and compared with normative data. Spinal radiographs were obtained to assess vertebral morphology. Blood biochemistry included vitamin D concentration and other parameters of calcium homeostasis.

Results Ten children (17%) had sustained in total 14 peripheral fractures; lower‐limb fractures predominated. Compression fractures were present in 25%. The median spinal BMAD z‐score was −1.0 (range −5.0 to 2.0); it was −0.6 in those without fractures and −1.7 in those with fractures (p=0.004). Vitamin D insufficiency was present in 59% of participants (serum 25‐hydroxyvitamin D <50nmol/l) and hypercalciuria in 27%. Low BMAD z‐score and hypercalciuria were independent predictors for fractures.

Interpretation Children with motor disability are at high risk of peripheral and vertebral fractures and low BMD. Evaluation of bone health and prevention of osteoporosis should be included in the follow‐up.
Learning from research on the information behaviour of healthcare professionals: a review of the literature 2004–2008 with a focus on emotion
Authors: Fourie Ina
Published: August 2009

Objective:  A review, focusing on emotion, was conducted of reported studies on the information behaviour of healthcare professionals (2004–2008). Findings were intended to offer guidelines on information services and information literacy training, to note gaps in research and to raise research interest.

Method:  Databases were searched for literature published from January 2004 to December 2008 and indexed on eric, Library and Information Science Abstracts, medline, PsycINFO, Social Services Abstracts, Sociological Abstracts, Health Source: Nursing/Academic Edition; Library, Information Science & Technology Abstracts; Psychology and Behavioral Sciences Collection; Social Work Abstracts; SocINDEX with Full Text; SPORTDiscus; cinhal; and the ISI Web of Knowledge databases. Key journals were manually scanned and citations followed. Literature was included if reporting on issues concerning emotion.

Results:  Emotion in information behaviour in healthcare contexts is scantily addressed. This review, however, offers some insight into the difficulty in identifying and expressing information needs; sense making and the need to fill knowledge gaps; uncertainty; personality and coping skills; motivation to seeking information; emotional experiences during information seeking; self‐confidence and attitude; emotional factors in the selection of information channels; and seeking information for psychological or emotional reasons.

Conclusion:  Suggestions following findings, address information literacy programs, information services and research gaps.
Population density and geographical range size in the introduced and native passerine faunas of New Zealand
Authors: Blackburn T. M. , Gaston K. J. , Duncan R. P.
Published: August 2009

The current avifauna of New Zealand comprises species with two distinct origins: those that evolved in New Zealand or colonized naturally from neighbouring landmasses, and those that were deliberately introduced to the islands by European settlers. Elsewhere, it has been shown that for species introduced to New Zealand from Britain there is a positive interspecific correlation between the geographical range sizes attained in both countries. Since positive relationships between abundance, measured either as population size or density, and geographical range size are a near ubiquitous feature of assemblages of closely related animal species, this suggests that species’ abundances may also be so correlated between the two countries. Here, data for 12 passerine bird species introduced to New Zealand from Britain are used to compare population densities and density–range size relationships in their native and alien ranges. In addition, the density–range size relationship for 12 passerine bird species that can be considered native to New Zealand is compared to that for the introduced species. The geographical range size and the mean and maximum densities of introduced species in New Zealand were significantly positively correlated with those values for the same species in Britain. However, in no case was the relationship between mean density and range size significant. While not statistically significant, density–range size relationships for introduced species are similar in New Zealand and Britain, but those for introduced and native species in New Zealand are quite different. Implications of these patterns are discussed.
EFFECTS OF CALCIUM ENTRY BLOCKERS ON BLOOD PRESSURE AND HEART RATE IN NEUROGENIC HYPERTENSIVE DOGS
Authors: MONTASTRUC P. , VALET P. , DANG TRAN L. , GAILLARD G. , MONTASTRUC J.L.
Published: August 2009

Summary—The hypotensive and negative chronotropic effects of 5 calcium entry blockers (verapamil 200 μg/kg IV; diltiazem 300 μg/kg IV; nifedipine 5 μg/kg IV; nicardipine 50 μg/kg IV; and bepridil 5 mg/kg IV) were compared in control normotensive and acute neurogenic hypertensive anaesthetized dogs. Acute neurogenic hypertension was induced by sino‐aortic denervation (SAD).

In control normotensive dogs, all drugs (except bepridil) induced a slight and transient decrease in blood pressure. Nifedipine and nicardipine increased heart rate whereas the three other drugs remained ineffective.

SAD caused a 2–2.5‐fold increase in the hypotensive properties of the 5 drugs in dogs. Moreover, the duration of this induced hypotension was longer than in control normotensive animals. In SAD dogs, all calcium entry blockers significantly decreased heart rate.

This study indicates that the direct cardiac inhibitory action of calcium channel blockers is modulated by baroreceptor activity in intact animals. The mechanism of the selective action of calcium entry blockers in hypertensive SAD in contrast to normotensive dogs is discussed.
SENSITIVITY OF PANCREATIC BETA CELL TO CALCIUM CHANNEL BLOCKERS. AN ELECTROPHYSIOLOGIC STUDY OF VERAPAMIL AND NIFEDIPINE
Authors: VASSEUR M. , DEBUYSER A. , JOFFRE M.
Published: August 2009

Summary—Microelectrodes were used to study the comparative effects of 2 calcium channel blockers on glucose‐induced electrical activity in mouse beta cells. In 2.8 mM glucose, verapamil (10−5M), but not nifedipine (10−7M), induces a silent depolarization. In 11.1 mM glucose, verapamil (10−7to 5.10−5M) induces continuous spike activity by a decrease in the maximum repolarization potential. Nifedipine (10−10to 10−6M) induces the same activity, but subsequent to a hyperpolarization of the cell at the maximal repolarization potential followed by a silent phase to the plateau potential. The 2 drugs induce a dose‐dependent decrease in spike frequency without any change in spike amplitude. In 22 mM glucose exposure to nifedipine, but not to verapamil, induces a transient period of slow‐wave activity. The 2 drugs induce a dose‐dependent decrease in spike frequency. At higher concentrations (nifedipine > 10−7M; verapamil > 10−6M) they induce the disappearance of spikes through a decrease in amplitude. These results show that the beta cell is more sensitive to nifedipine (ED50= 3 times 10−8M) than to verapamil, and that glucose stimulation increases the cell's sensitivity to verapamil (11.1 mM glucose: ED50= 10−5M versus 5times10−7M in 22 mM glucose) but not to nifedipine.
EFFECTS OF PROPRANOLOL AND SWIM‐TRAINING ON BLOOD PRESSURE, PLASMA ELECTROLYTES, AND VASOPRESSIN IN SPONTANEOUSLY HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: GHAEMMAGHAMI F. , GAUQUELIN G. , GEELEN G. , IBANEZ J. , BOUZEGHRANE F. , CHERBAL F. , MEUNIER C. , GHARIB C.
Published: August 2009

Summary—The aim of this work was to study the influence of beta‐adrenoreceptor blockade on the adaptation to exercise of one of the hormonal systems (arginine vasopressin) involved in the regulation of blood volume and pressure in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) was measured in SHR and WKY rats during 11 wk of swim training. At the end of the training program we determined post‐exercise values of plasma arginine‐vasopressin (pAVP), osmolality (pOsm), K+ (pK+), Na+ (pNa+), hemoglobin (Hgb), and hematocrit (Hct) in SHR and WKY rats. The following groups were studied: control (C), propranolol treated (PC), swim trained (S), and propranolol‐treated and swim‐trained (PS). SBP was significantly reduced by swim training or propranolol, bu these beneficial effects on SBP were attenuated when propranolol and swim training were combined. pNa+ and pOsm were significantly reduced by training alone in SHR. This reduction of pNa+ and, consequently, of pOsmol without any modification of other parameters could suggest an Na+ loss. In contrast, the SHR group treated with propranolol alone showed a significant reduction in Hct, suggesting an increased plasma volume without Na+ loss.

PS SHR showed a significant reduction of Hgb, Hct, proteins, pNa+, and pOsmol, probably as a consequence of the additive effects of swimming‐ and propranolol‐induced hypervolemia with Na+ loss. The slight and nonsignificant reduction in pAVP observed with either training or propranolol treatment alone became much more pronounced and statistically significant when the 2 treatments were combined. WKY rats showed a much smaller response to exercise and beta‐adrenoreceptor blockade than SHR.

We conclude that the hypervolemia suggested in PS SHR could be a possible cause of attenuation of the beneficial effects of either swimming or propranolol on SBP.
EFFECTS OF PURINES AND FORSKOLIN ON HAEMOLYSIS
Authors: GONÇALVES M.L. , RIBEIRO J.A.
Published: August 2009

Summary—Effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine on the antihaemolytic action of procaine, and the effect of ATP on the antihaemolytic actions of lidocaine, dibucaine, tetracaine, pentobarbitone, and chlorpromazine were investigated in rat erythrocytes. The effects of adenosine and its analogues d‐N6‐phenylisopropyladenosine (d‐PIA), l‐N6‐phenylisopropyladenosine (l‐PIA),N6‐cyclohexyladenosine (CHA), 2‐chloroadenosine, andN6‐methyladenosine, as well as the effects of cyclic‐AMP (cAMP), dibutyryl cAMP, and forskolin on haemolysis were also investigated in rat erythrocytes. ATP, ADP, and AMP, but not adenosine, antagonized in a concentration‐dependent manner the antihaemolytic action of procaine, and ATP was ineffective against the antihaemolytic actions of lidocaine, dibucaine, tetracaine, pentobarbitone, and chlorpromazine. Adenosine and its analogues, but notN6‐methyladenosine, protected erythrocytes against hypotonic haemolysis in a concentration‐dependent manner. The order of potencies was: d‐PIA>CHA> l‐PIA>adenosine>2‐chloroadenosine. The effect of adenosine on haemolysis was not prevented by theophylline, 8‐phenyltheophylline, or 8‐sulfophenyltheophylline. Dibutyryl cAMP, a stable analogue of cAMP, and forskolin, a specific activator of adenylate cyclase, mimicked the antihaemolytic action of adenosine. cAMP was less efficient than adenosine.

Adenine nucleotides antagonized the antihaemolytic action of procaine, probably due to calcium‐chelating properties. In contrast, adenine nucleosides have antihaemolytic properties. The possibility that the antihaemolytic effects of these substances relate to cAMP and/or to lipophilicity is discussed.
MAGNESURIA INDUCED BY THIAZIDES AND THE INFLUENCE OF TRIAMTERENE
Authors: LABEEUW M. , POZET N. , ZECH P. , HADJ‐AISSA A. , SASSARD J.
Published: August 2009

Summary—The effects on magnesium excretion of 4 short‐term diuretic treatments (methyclothiazide 2 mg either alone or associated with increasing doses of triamterene) were evaluated in 8 normal volunteers and compared to spontaneous variations during placebo administration. The thiazide exerted a small but significant magnesuric effect, which was prevented only by the lowest dose (25 mg) of triamterene. Larger doses had no protective effect on thiazide‐induced magnesuria. Independently of their absolute effects on magnesium excretion, all diuretics impaired the normal ability of the kidneys to compensate fully for the expected changes in magnesium reabsorption induced by extracellular volume contraction.
ANTIHYPERTENSIVE DRUGS AND BARORECEPTOR REFLEX CONTROL OF HEART RATE AND BLOOD PRESSURE
Authors: BERDEAUX A. , GIUDICELLI J.F.
Published: August 2009

Summary—The arterial baroreceptor reflex (BR; aortic and carotid sinus BR) and the cardiopulmonary BR are the most important reflexes acting as buffer systems for the maintenance of arterial pressure around a fixed physiologic value. They act as permanent inhibitory systems on the central cardiovascular structures and they can be either activated or deactivated by using selective techniques. During chronic hypertension there are structural alterations of the peripheral and/or central components of the BR that become «reset», with a shift in the function curve relating BR activity to blood pressure (BP) in the direction of higher pressure values. As a consequence of the hypertension‐induced resetting phenomenon, both the threshold pressure and sensitivity of BR are disturbed. However, if BR resetting during hypertension clearly decreases the sensitivity of BR control of heart rate (HR), BR control of peripheral resistance and arterial pressure as a whole is preserved and even increased when hypertension develops. Thus, this apparent discrepancy between BR control of HR and BP during hypertension demonstrates that evaluation of an antihypertensive therapy on reflex control of HR alone cannot predict what will happen to BR control of the whole cardiovascular system. Regarding BR control of HR, in contrast to the classical arteriolar vasodilators such as hydralazine and its derivatives, the majority of the modern antihypertensive drugs do not evoke reflex tachycardia in response to lowering of BP in normotensive or hypertensive subjects. Although the intrinsic pharmacologic mechanisms of action of these drugs on BR may be quite different (e.g., α1,‐or β‐adrenoreceptor blocking agents, converting enzyme inhibitors, certain calcium‐channel blockers of the phenyldihydropyridine group, and so on), they all shift in a parallel manner the set‐point of the BR response curve towards lower pressures, with no change in HR or R‐R interval. Generally, this resetting phenomenon occurs after several weeks or months of antihypertensive therapy, but it can also occur acutely (e.g.after IV injection) after administration of drugs such as prazosin or ketanserin. Finally, antihypertensive agents such as clonidine and methyldopa can simultaneously reset the BR and increase its sensitivity, thus leading to almost complete restoration of control of HR response despite the concomitant decrease in BP.

Regarding BR control of blood pressure, only captopril and especially celiprolol (a β1‐adrenoreceptor blocking drug with vasodilating properties) are able to restore almost normal BR control of arterial pressure.
IMMUNOPHARMACOLOGY OF THE IMMUNOTHERAPY OF CANCER, INFECTION, AND AUTOIMMUNITY
Authors: HADDEN J.W.
Published: August 2009

Summary— The current status and future prospects of the immunotherapy of cancer, infection, and autoimmunity are reviewed briefly. Progress in treating the immunodeficiency of cancer with thymic hormones and drugs such as levamisole and lentinan has produced some degree of remission stabilization. Interferon, interleukin II, and LAK cells have inhibited active, progressive cancer. New approaches with monoclonal antibodies, immunotoxins, tumor necrosis factors, and so on are under rapid development. Future prospects focus on combined approaches yielding synergy. Treatment of infections in animals and man either prophylactically or therapeutically, with thymic hormones, interferons, and thymomimetic drugs such as levamisole and isoprinosine, demonstrate the efficacy of this approach. The use of these agents in conjunction with antimicrobial therapy in immunosuppressed hosts is warranted. In immunodeficiency associated with AIDS virus infection, interleukin II, thymic hormones, isoprinosine, and imuthiol have shown effect in partially restoring immune function, although with little clinical benefit. Their use with antiviral therapy is advocated. Finally, thymic hormones, isoprinosine, levamisole, and other sulfur‐containing compounds have ameliorated murine and human autoimmune disease presumably through effects in improving cellular immune function. Continued development of this type of therapy is warranted. The continued progress of immunopharmacology as the science of immunotherapy portends the future successful development of many therapeutic approaches to these diseases.
EFFECTS OF BESTATIN AND PHOSPHORAMIDON ON THE HYPERTENSIVE RESPONSE TO PHYSOSTIGMINE IN THE RAT
Authors: DŽOLJlĆ E. , VARAGlĆ V.M.
Published: August 2009

Summary—Intracarotid (IC) injection of bestatin produced a dose‐dependent biphasic change in blood pressure (BP) of the rat, consisting of an initial short‐lasting fall followed by a long‐lasting increase. This effect was regularly depressed or abolished by IV injection of naloxone. IC injection of Leu‐enkephalin also produced a biphasic BP response, with the same characteristics as that produced by IC injection of bestatin. This effect was also easily blocked by IV injection of naloxone. IC injection of bestatin significantly potentiated the BP response to IC injection of Leu‐enkephalin. This potentiated response was blocked by naloxone. IC injection of both bestatin and phosphoramidon, whether separately or in combination, significantly depressed the hypertensive response to physostigmine. This depressive action of bestatin and phosphoramidon on physostigmine hypertension can be significantly antagonized or even reversed by IV injection of naloxone. IC injection of both bestatin and phosphoramidon did not affect the BP response to either acetylcholine or catecholamines. It is concluded that bestatin and phosphoramidon, injected into the carotid artery, inhibit the activity of aminopeptidase and «enkephalinase», thus producing an accumulation of enkephalins in the central nervous system. These enkephalins activate opioidergic receptors in the brain, but concomitantly produce a depression of the cholinergic‐adrenergic interaction in the central nervous system, which is known to be a prerequisite for the hypertensive response to physostigmine in the rat.
ELECTROPHYSIOLOGICAL ANALYSIS OF THE ACTION OF NIFEDIPINE AND NICARDIPINE ON MYOCARDIAL FIBERS
Authors: CHARNET P. , OUADID H. , RICHARD S. , NARGEOT J.
Published: August 2009

Summary—The effects of nifedipine and nicardipine, 2 dihydropyridines (DHP) used in the treatment of cardiovascular disorders, were compared in frog atrial fibers. Rapid photolysis of nifedipine with a single UV flash (1‐ms duration) reversed the block, allowing comparison of effects of both drugs on the same preparation, and manipulation of the calcium channel on a millisecond timescale. The results show that inhibition of the action potential (AP) and slow inward current (Isi) is more pronounced with nifedipine than with nicardipine. Concentration‐effect relationships confirm that nicardipine (IC50= 1 μM) is less potent than nifedipine (IC50= 0.2 μM) in blocking cardiac calcium channels. Both DHP block calcium channels in the closed state at the resting potential, inducing a large tonic block (in the absence of stimulation). An additional phasic block can be observed with nifedipine and nicardipine. A slight voltage dependence to the block is observed for both DHP, their effects being enhanced at depolarized holding potentials. Rapid unblocking of calcium channels by a single light flash, presented during the decay phase of Isi, reveals a higher affinity of DHP for inactivated channels. This effect is most pronounced when inactivation is slowed by using Ba+ +, Sr+ +, or Na+ ions as the current carriers. Open channel block is also suggested. The mechanism of DHP action on calcium channels can be described according to the «modulated receptor hypothesis». These DHP exhibit an additional nonspecific effect on potassium channels.

It is concluded that nicardipine is a less potent Ca+ +antagonist than nifedipine in atrial fibers and that the reduction of delayed potassium current, which occurs in a similar range of concentrations to the blockade of Isi, could also be involved in its therapeutic effects.
AN INVESTIGATION INTO THE POSSIBLE DEVELOPMENT OF CHRONIC TOLERANCE TO ANALGESIA AND DEPENDENCE ON PROLACTIN
Authors: RAMASWAMY S. , VENKATADRI N. , BAPNA J.S.
Published: August 2009

Summary— The possibility of the presence of chronic tolerance to the analgesic effect of prolactin and of dependence was tested. Repeated administration of prolactin resulted in the loss of analgesic activity, indicating the development of chronic tolerance. Neither a high dose of, or chronic treatment with prolactin followed by naloxone elicited any characteristic withdrawal signs, suggesting the absence of dependence. Similarly, abrupt withdrawal of prolonged prolactin treatment also did not elicit withdrawal signs. However, in the same model, the morphine‐naloxone combination and spontaneous withdrawal of chronic morphine treatment produced characteristic withdrawal signs, namely jumping, wet shakes, and body tremor. The data support the view that tolerance and dependence can be dissociated from each other and that different mechanisms may operate in these phenomena. The absence of liability to dependence with prolactin strengthens the contention that prolactin may be a potential drug for combatting opiate dependence.
EFFECTS OF ORAL PRAZOSIN ON TOTAL PLASMA DIGOXIN LEVELS
Authors: ÇOPUR S. , TOKGÖZOĜLU L. , OTO A. , ORAM E. , UĜURLU Ş.
Published: August 2009

Summary— Prazosin and digoxin are frequently coadministered in clinical practice. To determine the effects of oral prazosin treatment on steady‐state digoxin levels, 20 patients receiving a constant maintenance dose of digoxin, who had normal renal and liver functions and were not receiving any other treatment, were given 5 mg of prazosin for 3 days. Plasma digoxin levels were measured before, on days 1 and 3 of prazosin treatment, and after prazosin had been discontinued. It was found that prazosin significantly increased plasma digoxin levels. On discontinuation of prazosin digoxin levels returned to their previous values.
INHIBITION OF THE COLONIC MOTOR RESPONSE TO EATING BY PINAVERIUM BROMIDE IN IRRITABLE BOWEL SYNDROME PATIENTS
Authors: FIORAMONTI J. , FREXINOS J. , STAUMONT G. , BUENO L.
Published: August 2009

Summary— The effect of pinaverium bromide on the colonic motor response to eating was investigated in 10 irritable bowel syndrome patients, by means of an intraluminal probe supporting 8 groups of electrodes. At each site examined from transverse to sigmoid colon, the electromyograms exhibited 2 kinds of spike bursts: short spike bursts (SSB) localized at one electrode, and long spike bursts (LSB), isolated, propagated orally or aborally over a few centimeters, or aborally propagated over the whole length of the colon investigated (migrating long spike bursts, MLSB). Recordings were continously performed over 24 hr. Each patient received at 7.00 p.m. on day 1 and at noon on day 2 an 800–1000 Kcal meal preceded by IV administration of pinaverium bromide (4 mg) or placebo.

After placebo administration, the duration of LSB activity and the number of MLSB were significantly increased over 3 postprandial hr by comparison with the 2 hr preceding the meal. After pinaverium injection no significant postprandial change in LSB and MLSB activity was noted. The SSB activity was not modified after the meals preceded by placebo or pinaverium injection.

These results suggest that the inhibitory action of pinaverium bromide on postprandial colonic motility may support the clinical efficacy of this agent in the treatment of the irritable bowel syndrome.
PHARMACOKINETIC INTERACTION BETWEEN NIFEDIPINE AND PROPRANOLOL
Authors: ZYLBER‐KATZ E. , TURETZ‐ABRAMOVITCH M. , KOREN G. , LEVY M.
Published: August 2009

Summary— In 8 healthy volunteers, single‐dose nifedipine pharmacokinetics were compared with and without the coadministration of propranolol.

An elevation of the mean Cmax was found, from 73.9±14.1 when nifedipine was taken alone, to 115.7±12.1 (SE) ng/ml (P<0.02) when the agent was combined with propranolol. The AUC0‐∞ increased as well, from 287.1±33.5 to 363.0±54.3 (SE) (μg.hr)/1 (P<0.01), indicating an increase in bioavailability. Propranolol treatment did not significantly affect the nifedipine half‐life (α or β phase) or the estimated volume of distribution, whereas systemic clearance tended to decrease in 6 of the subjects.

The most likely explanation for increased bioavailability of nifedipine when coadministered with propranolol is by a reduction of the hepatic ± first‐pass ± clearance, as a result of changes in hepatic blood flow.
RABBIT ARTICULAR CHONDROCYTES: AN IN VITRO MODEL FOR STUDYING THE EFFECT OF SODIUM AURO‐THIOPROPANOL SULFONATE ON PROLIFERATION KINETICS, TYPE II COLLAGEN PHENOTYPE AND MITOCHONDRIAL ACTIVITY
Authors: RONOT X. , HAINQUE B. , CHRISTEN M.‐O. , FROGER B. , HARTMANN D.J. , ADOLPHE M. , LECHAT P.
Published: August 2009

Summary— Despite the benefits of chrysotherapy the responsible mechanism of action of gold compounds remains unclear. At a concentration of 5 times 10−4 M, sodium aurothiopropanol sulfonate (SAS) modified the in vitro proliferation kinetics of articular chondrocytes by reducing growth, viability and plating efficiency. Flow cytometry analysis, using propidium iodide DNA staining, revealed slight but significant cell arrest in G2 + M which, in fact, represents an increase in the proportion of binucleate cells. SAS did not induce any variations in chondrocyte phenotype stability as far as the biosynthesis of type II collagen was concerned, and no appreciable changes in overall mitochondrial activity reflected by rhodamine 123 incorporation.
A NEW ENDOGENOUS ANXIOLYTIC AGENT: l‐PYROGLUTAMIC ACID
Authors: BENI M. , PELLEGRINI‐GIAMPIETRO D.E. , MORONI F.
Published: August 2009

Summary—By use of a simple anticonflict procedure (Vogel test), it was demonstrated that l‐pyroglutamic acid (l‐pyrrolidone carboxylic acid [l‐PCA]), an amino acid naturally occurring in mammalian tissues and fluids, possesses anxiolytic activity. This effect was stereospecific (d‐PCA was inactive) and, in the rat, it was not associated with a decrease in motor activity. Ro 15–1788, a benzodiazepine antagonist, did not modify l‐PCA actions. Furthermore, anxiolytic doses of the amino acid did not change the content of 5‐hydroxytryptamine (5‐HT) or of 5‐hydroxyindoleacetic acid (5‐HIAA) in the rat cortex and hippocampus.

These results suggest that the mechanism of the anxiolytic activity of l‐PCA is different from that of the benzodiazepines and of 5‐HT1aagonists.
NO EVIDENCE OF VASCULAR DOPAMINE RECEPTORS IN THE RAT PORTAL VEIN
Authors: VIDAL‐BERETERVIDE K. , DECKER N. , SCHMIDT M.
Published: August 2009

Summary—Dopamine (5.3 times 10−6to 5.3 times 10−5M) decreased the force of spontaneous myogenic contractions of the rat portal vein in a concentration‐dependent manner in the presence of the alpha‐adrenoreceptor antagonist BE‐2254. The DA1‐selective agonist fenoldopam and the DA2‐preferential agonist (‐)‐EOE were both inactive. Dopamine‐induced relaxation was not inhibited by (+)‐butaclamol (10−8M), but was reduced by a potent beta2‐selective adrenoreceptor antagonist ICI 118,551 (2times10−8M). Our results demonstrate that the rat portal vein is devoid of postsynaptic DA1and DA2dopamine receptors.
CLINICAL EVALUATION OF THE CARDIOVASCULAR EFFECTS AND THE PHARMACOKINETICS OF BENALFOCIN AND ITS METABOLITE IN HEALTHY SUBJECTS DURING REPEATED DOSING
Authors: KERTH P. , FRISK‐HOLMBERG M.
Published: August 2009

Summary—The cardiovascular effects and the pharmacokinetics of a new selective alpha‐2 adrenoceptor antagonist, benalfocin, and its active metabolite, both compounds with a similar receptor affinity profile, were examined in healthy volunteers during repeated dosage. Significant diastolic blood pressure lowering effects were observed on the first and the last day of the treatment persisting throughout the dosage interval. Furthermore, heart rate reductions were found on these days which were significantly correlated with both the parent compound's and the metabolite's plasma concentrations and their sum. Pharmacokinetics remained unchanged after a 1‐wk oral dosing as compared to a single oral dose; the plasma half‐life of the metabolite was 3‐fold longer than that of the parent compound. In normotensive subjects, benalfocin produced blood pressure and heart rate reducing effects, the latter being more correlated with the metabolite's plasma concentrations. Furthermore, results suggest that the compound's known cholinergic effects may be particularly related to the metabolite and that this molecule is an interesting cardiovascular compound.
BLOOD BINDING AND TISSUE UPTAKE OF DRUGS. RECENT ADVANCES AND PERSPECTIVES
Authors: TILLEMENT J.‐P. , URIEN S. , CHAUMET‐RIFFAUD P. , RIANT P. , BREE F. , MORIN D. , ALBENGRES E. , BARRE J.
Published: August 2009

Summary—The free drug hypothesis, which states that only the unbound moiety of drug in blood is available for tissue diffusion, is discussed according to recent investigations. In some experimental conditions, it must be assumed that part of the protein‐bound drug in plasma is extracted during a single passage through the organ studied. The mechanisms underlying these observations are not unequivocal and remain hypothetical. In the liver, high‐affinity binding sites for serum albumin have been demonstrated, and they would explain the high extraction by liver of endogenous and exogenous compounds.

However, these experiments measure the unidirectional transfer of a drug from the vascular to the extravascular space in non‐steady‐state conditions. Hence, in steady‐state conditions, the free drug hypothesis cannot be ruled out because it is supported by numerous pharmacokinetic studies.
ACUTE RELEASE OF CATECHOLAMINES ON CIRCULATING BLOOD CELL ADRENOCEPTORS AND METABOLIC INDICES IN DOG
Authors: VALET P. , DAMASE‐MICHEL C. , TAOUIS M. , MONTASTRUC J.L. , COTONAT J. , MONTASTRUC P.
Published: August 2009

Summary—The effects of acute release of endogenous catecholamines on both platelet alpha2and leukocyte beta adrenoreceptors and metabolic indices (glucose and free fatty acids) were investigated in dogs by means of a model of neurogenic hypertension following acute sinoaortic denervation (ASAD). Despite the marked increase in catecholamine levels (+4.2‐fold for noradrenaline and 16.7‐fold for adrenaline, for example, at minute 45 following ASAD) and in glucose plasma levels, and the significant decrease in free fatty acid plasma levels, no change in platelet alpha2or leukocyte beta adrenoreceptor binding sites (number as well as affinity) was observed during the whole experiment. It is suggested that the number of platelet alpha2‐ and leukocyte beta‐adrenoreceptors is not submitted to short‐term regulation, at least by endogenous catecholamines in dogs.
BETA‐BLOCKING ACTIONS OF BETAXOLOL ON THE ISOLATED RAT PORTAL VEIN
Authors: VIDAL‐BERETERVIDE K.
Published: August 2009

Summary—The characteristics of the β‐adrenoceptor population mediating the actions of noradrenaline and isoproterenol in the rat portal vein were examined in comparison with those in the rat atria.

In the portal vein, the pA2values obtained for the selective β1‐adrenoceptor antagonist betaxolol were 100‐fold lower than those obtained in the atria, suggesting that in the rat portal vein a population of β2‐adrenoceptors is highly predominant.