bluuebunny/crossref_metadata_2025 huggingface dataset:
Music, media and making: Humanising digital media in music education
Authors: Brown Andrew R.
Published: March 2007

This paper examines three functions of music technology in the study of music. Firstly as a tool, secondly as an instrument and lastly as a medium for thinking. As our societies become increasingly embroiled in digital media for representation and communication, our philosophies of music education need to adapt to integrate these developments while maintaining the essence of music. The foundation of music technology in the 1990s is the digital representation of sound. It is this fundamental shift to a new medium with which to represent sound that carries with it the challenge to address digital technology and its multiple effects on music creation and presentation. In this paper I suggest that music institutions should take a broad and integrated approach to the place of music technology in their courses, based on the understanding of digital representation of sound and these three functions it can serve. Educators should reconsider digital technologies such as synthesizers and computers as music instruments and cognitive amplifiers, not simply as efficient tools.
Social Psychology, Competency, and Individual Differences in Communicative Action
Authors: Delia Jesse G.
Published: March 2007

The generativist conception of linguistic competence and its idealisa tion of a homogeneous speech community must be overcome if analyses of individual differences in language and communication are to receive the attention they merit. Development of a qualitative, multiple competencies conception of linguistic and communicative abilities offers promise of transcending the limita tions of the generativist approach while maintaining its concern with fundamental form-meaning covariations in language usage. Within such an expanded concep tion of competence, an interpretive-contextual social psychology can make im portant contributions to our understanding of individual differences in communi cative action.
The Management Structure Review
Authors: Waters Robert , Kirkpatrick Jenny , Wells Owen , Carney A.M.
Published: March 2007

The Management Structure Review (MSR for short) is an important document because it is likely to have a major influence on the future shape, structure and style of the organisation of the Probation Service. That means that the lives of probation officers and the service they offer to the public may be crucially affected by decisions made on the basis of it. It is vital that its conclusions and recommendations be widely and thoroughly debated. (They were summarised in the NAPO Newsletter for September 1980).

In the following pages we print contributions representing a range of views of the MSR. We cannot hope to represent all views, but hope that others will be moved to continue the debate among colleagues, in branches, and in these pages. It may be a long time before these issues are again discussed nationally, and we must not miss the opportunity of having a voice in a vital aspect of our future. That voice may be heard most strongly by representation of views to HQ through branches.
What about the Workers?
Authors: Varah M.
Published: March 2007

Without making any claims for sophisticated research methods, the author reports the results of a simple survey of offenders' opinions of their community service experience. It may not be the most respectable piece of research we've ever printed, but it brings the clients' voices clearly and significantly into our pages.
Community Service as a Tariff Measure
Authors: Godson D.
Published: March 2007

Anyone caring to review recent literature on the use of community service as a direct alternative to custody might well conclude that it is failing as a tariff measure. In this article the author poses two questions which are directly relevant to this growing debate. Firstly, how valid is this conciusion in the light of differing sentencing policies amongst schemes? Secondly, where the policy is clearly to use community service as a tariff sentence, how can the number of offenders diverted from custody be adequately estimated?
Implementing an information strategy for sub-Saharan Africa: the first stages
Authors: Camara Alioune Badara
Published: March 2007

The seventh (final) in a series of articles on the activities of the Information Sciences Division (ISD) of the International Development Research Centre (IDRC). Describes the information strategy for sub- Saharan Africa evolved by the Division. On the basis of almost two decades of experience in the region, ISD is in the process of implementing this strategy to provide more effective support to information systems, networks and services in sub-Saharan Africa. Gives a brief overview of ISD experience in the region and discusses how the strategy was drawn up, its main features and the first stages of its implementation. Although the strategy's objectives do not represent a radical difference from the Division's past activities in Africa, it puts more emphasis on the information needs of the urban and rural poor and development practitioners. Also stressed are the importance of indigenous knowledge, appropriate feedback mechanisms and human resources development.
Postgraduate research trends in Ethiopia
Authors: Gabre-Tsadik Degife , Gupta Sushma
Published: March 2007

Briefly reviews the development of higher education in Ethiopia and analyzes the postgraduate theses submitted to Addis Ababa University from 1980 to 1987. Concludes that remarkable progress in encouraging postgraduate research has been achieved in the university during a comparatively short period of time.
Selecting software for a development information database
Authors: Geethananda Hemamalee
Published: March 2007

Presents a case study of the Development Information Network for South Asia (DEVINSA) in the selection of the most suitable software package for the establishment and development of its master database located at the Marga Institute in Colombo, Sri Lanka. Examines some of the attributes and characteristics of two software packages for microcomputer use, INMAGIC and CDS/ISIS, in developing a structured bibliographical database. The criteria for selection are formulated in relation to the needs, activities, services, type of data and users of the DEVINSA system.
Information needs of rural women in Nigeria
Authors: Nwagha Georgiana K. N.
Published: March 2007

Some factors contributing to the low standard of living of rural people in Africa in general and rural women in particular, are discussed, and the ineffectiveness of the various governments' programmes to redress the situation highlighted. A survey conducted in Nigeria reveals that rural women, who are predominantly illiterate, are ignorant of modern methods of improving agricultural production and of other ways of self- development. The dissemination of vital information that could assist rural dwellers to improve themselves and their economic status, is recommended as an effective means of rural development. The use of radio jingles is also recommended to make information dissemination to rural people effective.
Meeting the needs of agricultural researchers in Africa: the role of unpublished reports
Authors: Kaniki Andrew M.
Published: March 2007

Edited version of a paper presented at the Pan African Institute for Development - Eastern and Southern Africa (PAID - ESA) Seminar on the Role of Unpublished Reports in Information and Documentation, Kabwe, Zambia, 8 - 9 January 1991. Agricultural researchers often experience problems in the course of their work. These problems often manifest themselves as information needs. If these needs are fulfilled, researchers can conduct quality research and generate utilizable information. This information can then be used by end-users such as farmers to boost agricultural production and thus enhance the general development of a country. One useful but under-utilized source of agricultural information is that of unpublished reports. Information professionals can help bridge the gap between the information contained in such reports and the information needs of agricultural researchers. Identifies the information needs of agricultural researchers in Africa, looks at unpublished reports as such and disc sses ways in which information professionals can assist agricultural researchers to use such reports to meet their information needs.
The psychopharmacology of the human pineal
Authors: Checkley S.A. , Park S.B.G.
Published: March 2007

In many ways the pineal is an ideal endocrine gland for the biological psychiatrist. The gland is small, circumscribed and relatively homogeneous, so it can be studied either in tissue culture or in vivo. The results from such studies combine to give a well-characterized model for investigating noradrenergic neurotransmission. In the pineal as in the brain there is a noradrenaline uptake site, an autoreceptor which regulates noradrenaline release, and there are post-junctional β1 and α1-adrenoceptors. In the pineal as in the brain the β1 adrenoceptor is linked to adenylate cyclase and the α 1-adrenoceptor is coupled with phos phatidyl inositol (PI) turnover: both second messenger systems combine to influence mela tonin secretion.
Low tolerability of carbamazepine in psychiatric patients may restrict its clinical usefulness
Authors: Elphick M. , Lyons F. , Cowen P.J.
Published: March 2007

There are reports of prophylactic efficacy of carbamazepine (CBZ) in manic depres sives when compared with placebo and chlorpromazine. Following a successful open pilot study by one of the authors, an attempt was made to compare carbamazepine and lithium carbonate in a double-blind, crossover trial, each patient being assigned to take each drug for 9 months in random order. However, of the first 14 patients to take carbamazepine four were withdrawn because of drug rashes and another two because of other adverse effects. The trial was discontinued, and a casenotes survey of 50 consecutive psychiatric patients who had been prescribed carbamazepine for mood disorders was then carried out, to establish the tolerability of the drug in clinical practice. Of these, 22 per cent had suffered dizziness, nausea or unsteadiness despite slow introduction of doses. Drug rashes occurred in 16 per cent of patients within the two weeks of starting treatment. A further 14 per cent had other unwanted effects. In total, 36 per cent of the patients had the drug stopped because of adverse effects. With regard to efficacy, in those taking the drug for more than 4 weeks, clinicians reported a definite or probable advantageous effect in 62 per cent of the sample, definite or probable lack of effect in 19 per cent and no opinion in 19 per cent. This low tolerability is not in accordance with previous reports of 2-6 per cent incidence of drug rashes and 10 per cent overall intolerance in neurological patients. We conclude that tolerability is a major drawback to the use of carbamazepine in some groups of psychiatric patients, although all the side- effects were reversible. However, clinical impressions suggested that in a number of patients no other therapeutic strategy was as effective in preventing mood swings.
Potentiation of the pressor effect of oral and intravenous tyramine during administration of the selective MAO-A inhibitor moclobemide in healthy volunteers
Authors: Wijnands S. , Chang P.C. , Blauw G.J. , van den Krogt J. , Gieschke R. , Schoerlin M-P. , van Brummelen P.
Published: March 2007

The interaction between tyramine and the new short-acting and reversible mono amine oxidase inhibitor moclobemide was investigated in a double-blind placebo-controlled study in six healthy volunteers. There were two consecutive study periods of 8 days during which the subjects received moclobemide three x 200 mg daily or placebo. On day 5 of each study period changes in systolic blood pressure (SBP) were determined after incremental intravenous bolus doses of tyramine and on days 6, 7 and 8 changes in SBP were determined after oral tyramine (100, 200 and 300 mg, respectively). Oral tyramine was administered together with a standard breakfast, before which moclobemide had been given. On days 5- 8 blood was taken for determination of blood drug levels. On days 6-8 blood samples were taken before and at 15, 30 and 45 min after tyramine administration for determination of plasma tyramine and plasma norepinephrine concentrations. When SBP had increased by approximately 30 mmHg no further doses of either intravenous or oral tyramine were given. Moclobemide was well tolerated by all subjects. Plasma trough levels of moclobemide were within the therapeutic range. The tyramine induced increases in SBP were greater during moclobemide than during placebo. After intravenous tyramine the dose-response curve for SBP was shifted to the right by a factor of approximately 3. When compared to placebo the pressor response to 100 mg tyramine orally was not significantly different, but the pressor response to the other two doses was enhanced during moclobemide.
Biphasic effects of propranolol on extinction of rewarded responding
Authors: Salmon Peter
Published: March 2007

The effect of propranolol (5 mg/kg intraperitoneally) was investigated on the extinction of: (i) lever-pressing reinforced on a random interval (RI 64 s) schedule; and (ii) continuously reinforced running (1 min intertrial interval). Although there was evidence of an initial effect in each case to facilitate responding (increased rate of lever-pressing or speed of running), the opposite effect emerged as extinction continued; that is, propranolol promoted extinction. These results are inconsistent with the author's hypothesis, suggested by earlier studies, that acute administration of propranolol antagonizes the inhibitory effects of non- reward on behaviour.
Clinical pharmacology of moclobemide, a new reversible monoamine oxidase inhibitor
Authors: Warrington S.J. , Turner P. , Mant T.G.K. , Morrison P. , Haywood G. , Glover V. , Goodwi B.L. , Sandler M. , John-Smith P. St. , McClelland G.R.
Published: March 2007

The clinical pharmacology of the new reversible monoamine oxidase (MAO) inhibitor, moclobemide, was examined in three separate studies in healthy male volunteers. In a single oral dose study, moclobemide (25-150 mg) was rapidly absorbed from the gastrointestinal tract and had a relatively short plasma half-life (mean 1.3 h after 150 mg). A decrease in the plasma concentrations of the noradrenaline metabolite 4- hydroxy-3-methoxyphenylglycol (HMPG), however, indicated a longer time to peak pharmacodynamic effect and longer duration of activity. Assay of platelet MAO activity did not reveal any evidence of irreversible inhibition of the B form of the isoenzyme. Single oral doses of moclobemide (150 and 300 mg) significantly lowered the threshold to the cardiovascular effects ('cheese reaction') of intravenous tyramine. However, after repeated administration of 100 mg three times daily for over 2 weeks, moclobemide caused significantly less potentiation than did phenelzine (15 mg three times per day) on the cardiovascular effects of oral tyramine, a clinically more relevant model. The MAO-B inhibitor, selegiline (5 mg once daily), also lowered the oral tyramine threshold significantly. Moclobemide was generally well tolerated by these healthy volunteers.
Long-term administration of m-chlorophenylpiperazine to rats does not alter functional sensitivity of either pre-synaptic or postsynaptic 5-HT1A receptors
Authors: Aulakh Charanjit S. , Hill James L. , Tolliver Teresa J. , Marcantonio David , Murphy Dennis L.
Published: March 2007

Administration of the selective 5-HT1A agonist, 8-hydroxy-2(di- n-propylamino)tetralin (8-OHDPAT ), to rats produced increases in food intake in freely fed animals and decreases in food intake in food-deprived animals. Acute pre-treatment with various doses of m-chlorophenylpiperazine ( m-CPP, another 5-HT agonist) attenuated 8-OHDPAT-induced increases in food intake in the free-feeding paradigm and enhanced 8- OHDPAT-induced decreases in food intake in the food-deprived paradigm. In the two paradigms, however, neither increases nor decreases in food intake induced by 8-OHDPAT were altered in animals following long- term (21-day) treatment with m-CPP versus saline when animals were challenged with 8-OHDPAT 48 h after the last dose of m-CPP. These findings suggest that long-term m-CPP treatment does not alter the functional sensitivity of 5-HT1A receptors located pre-synaptically that mediate hyperphagia or 5-HT1A receptors located post-synaptically that mediate decreases in food intake by induction of the serotonin behavioural syndrome.
Memory functions, alertness and mood of long-term benzodiazepine users: a preliminary investigation of the effects of a normal daily dose
Authors: Curran H. Valerie
Published: March 2007

The effects of a normal daytime dose of a benzodiazepine (BZ) on memory functions and mood were assessed in 20 out-patients who had taken BZs regularly for an average of 10 years. The results implied that these chronic users may have developed tolerance differentially to the sedative, anxiolytic and amnesic effects of one dose of BZ. A daytime dose did not produce subjective sedation. Lack of change in psychomotor performance and certain memory measures may either show tolerance or imply that the drug counteracts a possible practice effect. Anxiety levels decreased markedly after a daily dose, but this does not necessarily imply a purely pharmacological effect. Memory impairments were apparent in terms of increased susceptibility to proactive interference. This impairment was significantly correlated with the dosage of BZ taken.
ECT treatment does not enhance neuroendocrine responses to serotonergic challenge
Authors: Manji Husseini K. , Hsiao John K. , Risby Emile D. , Osman Ossama T. , Rudorfer Matthew V. , Potter William Z.
Published: March 2007

We prospectively investigated the effects of a course of electroconvulsive therapy (ECT) on neuroendocrine responses to serotonergic challenge in five depressed patients. Low dose intravenous chlorimipramine (CMI) challenge produced a modest release of prolactin and significant increases in plasma adrenocorticotrophic hormone (ACTH) and cortisol. Interestingly, ECT did not alter the neuroendocrine responses to serotonergic challenge despite clinical response in four of the five patients. If anything, the modest prolactin (PRL) response to CMI, rather than being enhanced, appeared to be abolished following ECT. Using confidence intervals, we estimate that there is less than a 5% probability of a 78% increase in prolactin response to CMI after ECT. To detect this, a sample size of greater than 35 would be needed. These findings suggest that neither ECT nor the clinical response in severely depressed patients is likely to produce consistent changes in neuroendocrine response to the acute serotonergic effects of CMI infusion. The lack of effect of ECT on prolactin response to serotonergic challenge might be explained by simultaneous enhancement of both serotonergic and dopaminergic neurotransmission.
Effects of ethanol on psychomotor performance under steady-state conditions
Authors: Fagan D. , Tiplady B. , Scott D.B.
Published: March 2007

Ethanol was administered to eight male volunteers using an oral loading dose followed by repeated small oral doses to achieve approximate steady-state drug concentrations in a double-blind placebo controlled cross over design. Ethanol or placebo were administered over a 5-h period in two sessions at least 7 days apart. The effects of ethanol were assessed using a short battery of psychomotor tests and visual analogue scales which was administered repeatedly during the steady-state period, and a long battery administered once before and once during the steady-state period. The concentrations of ethanol in plasma and breath were determined at 20-min intervals. Mean plasma concentrations of 94 mg/100 ml were obtained. Ethanol produced a clear impairment to psychomotor performance, with a 41% increase in body sway, a 61% increase in errors on a maze task, a 6.5% reduction in digit-symbol substitution and an 8% slowing in tapping. Subjective feelings of drunkenness and sedation were noted. No measure showed evidence for acute tolerance, as assessed by comparison of the slopes fitted to the performance measures in the short battery.
Behavioural effects of scopolamine and the TRH analogue RX77368 on radial arm maze performance in the rat
Authors: Watson C.D. , Hewitt M.J. , Fone K.C.F. , Dickinson S.L. , Bennett G.W.
Published: March 2007

Effects of repeated intracerebroventricular administration of the thyrotrophin-releasing hormone (TRH) analogue, RX77368 (3,3'-dimethyl-TRH, 2 μg, once daily), on a scopolamine-induced performance deficit in an eight-arm radial maze were evaluated in adult rats. Scopolamine (0.3 mg/kg i.p.—30 min) pre-treatment produced a significant deficit in the number of unrepeated arm entries and total arm entries and increased the percentage of incorrect arm entries and the total time on the maze, compared with saline-treated controls. Prior treatment with RX77368 (40 min before maze testing) produced a partial but significant attenuation of the scopolamine-induced performance deficit on the maze during the first five trials but RX77368 also enhanced maze performance during the same period when given alone. These results suggest that the observed scopolamine-induced performance deficit on the radial arm maze partly results from a reduction in locomotion and maze exploration rather than solely impairment of memory, and that RX77368 treatment may improve radial maze performance by increasing arousal and exploratory behaviour in rats rather than directly enhancing cognition.
The effect of temazepam on melatonin secretion and light sensitivity
Authors: Allen N.H.P. , Smythe P.J. , Martin N. , Plaskett L. , Osola K. , Childs P. , Thompson C.
Published: March 2007

Seven healthy male volunteers had their light sensitivity (melatonin suppression) and melatonin phase measured before and after treatment with temazepam (20 mg) for 7 days. Temazepam did not alter the circadian phase of melatonin secretion (the Dim Light Melatonin Onset, the timing of the peak of secretion), the total melatonin secretion nor the sensitivity of melatonin secretion to suppression by full spectrum light. This is an important negative finding which suggests that the short half-life benzodiazepine hypnotic temazepam does not confound tests of light sensitivity or melatonin phase.
In vivo effects of carbamazepine and haloperidol on GABA neurotransmission and LH secretion
Authors: Wolf Rainer , Strehle Franz , Emrich Hinderk M.
Published: March 2007

The in vivo effects of carbamazepine (CBZ) and haloperidol (HAL) on the neuroendocrine pre-optico-pituitary feedback system were studied by local application of the drugs, in single and in combination mode, through a push-pull cannula into the pre-optic area and measurement of their local effects on γ-aminobutyric acid (GABA) and their distant effects on a subsequent biological response: the pituitary luteinizing hormone (LH) secretion. The perfusion flow rate was 20 μl cerebrospinal fluid (CSF)/min; the fraction period was 15 min. Perfusion with 8 μg CBZ/ml CSF caused a reduction in pre-optic pre-synaptic GABA release and, concomitantly, a suppression of plasma LH levels. Application of 100 ng HAL/ml CSF also caused a reduction in GABA release, but no significant change in plasma LH levels. During the combined perfusion, the effects of CBZ and HAL did not add up with regard to the pre-optic GABA release. These results suggest that both drugs interact with the GABA system, but they may involve two different mechanisms of action. Due to the known inhibitory role of pre-optic GABA in pituitary LH secretion, it can be inferred that, in contrast to HAL, CBZ increases post-synaptic GABAergic transmission.
Clozapine can cause hallucinations by inducing complex partial seizures of temporal lobe origin (temporal lobe epilepsy). A potentially serious complication in the management of schizophrenia with clozapine
Authors: Geaney David
Published: March 2007

A young man with schizophrenia had persistent auditory hallucinations which responded well to clozapine but subsequently developed a different pattern of brief, joint visual and auditory hallucinations which were confirmed as being due to complex partial seizures of temporal lobe origin. He had no history of epilepsy prior to taking clozapine and the subsequent hallucinations could be mistaken for a deterioration in the schizophrenia, leading to a further increase in clozapine dose.
The 5-HT3 antagonist ondansetron reduces gastrointestinal side effects induced by a specific serotonin re-uptake inhibitor in man
Authors: Bailey Jayne E. , Potokar John , Coupland Nick , Nutt David J.
Published: March 2007

The selective serotonin re-uptake inhibitors (SSRIs) are increasingly being used to treat depression and anxiety disorders. Gastrointestinal (GI) symptoms are the main side effects, probably resulting from the stimulation of central or peripheral 5-HT receptors. The present double-blind, placebo-controlled study was undertaken to see if the GI side effects of fluvoxamine could be attenuated by the co-administration of the 5-HT3 antagonist ondansetron. The results demonstrate that, in volunteers, a single 100 mg oral dose of fluvoxamine can produce GI symptoms. Co-administration of ondansetron significantly reduced peak nausea and GI side effects, compared with placebo.
The effects of remoxipride and chlorpromazine on eye movements and psychomotor performance in healthy volunteers
Authors: King D.J. , Best P. , Lynch G. , Mannion M.F. , Montgomery R.C. , Tiplady B. , Yisak W.
Published: March 2007

Fifteen healthy male volunteers received single doses of 100 mg immediate release remoxipride (IR), 150 mg controlled release remoxipride (CR), 50 mg chlorpromazine (CPZ), 2 mg lorazepam (LZ), and placebo in a randomised, five-period cross-over study. Both saccadic (SEM) and smooth pursuit eye movements (SPEM) as well as a battery of psychomotor performance tests were assessed at 1.5-h intervals over 9 h following drug administration. The areas under the response-time curves and the maximum effect during the study period were analysed by analysis of variance. The most consistent impairments were produced by LZ. The neuroleptics caused impairments to SEM, and tended to impair critical flicker fusion, continuous attention and both paced and unpaced versions of the digit-symbol substitution test as well as subjective measures of sedation. Only LZ impaired SPEM. Neither paced nor unpaced psychomotor tests distinguished between neuroleptics and benzodiazepines. The low therapeutic doses of IR and CR produced similar impairments to a sub-therapeutic dose of CPZ. Selectivity of pharmacological action does not appear to predict selectivity of effect on psychomotor function.
The 5 -HT3 receptor antagonists, granisetron and ondansetron, do not affect cocaine-induced shifts in intra-cranial self-stimulation thresholds
Authors: Hatcher J.P. , Boyland P. , Hagan J.J.
Published: March 2007

The effects of the 5-HT 3 receptor antagonists, granisetron and ondansetron, were investigated on behaviour maintained by intracranial self-stimulation (ICSS). Rats, implanted with bipolar electrodes in the lateral hypothalamus, were trained to lever press on a continuous reinforcement schedule for positively reinforcing trains of electrical stimulation. The frequency at which responding reached 50% of maximum (M50) and the maximum rate of responding (asymptote) were used to measure drug effects. Granisetron (0.01-0.1 mg/kg i.p ) and ondansetron (0.03-0.3 mg/kg i.p ) had no effect on either parameter. In contrast, cocaine (20 mg/kg i.p ) potentiated rewarded responding, reducing M50 values, but neither granisetron (0.01-3.0 mg/kg i.p ) nor ondansetron (0.03-0.3 mg/kg i.p ) blocked this effect. Neither did granisetron (0.1-10.0 mg/kg i.p ) alter the effect of lower doses of cocaine (10 mg/kg i.p.). These data suggest that 5 -HT 3 receptors do not play a significant role in mediating responding maintained by ICSS in the rat through hypothalamic electrodes. Neither do they modulate cocaine-induced potentiation of the behaviour.
The effect of chlorpromazine and benzhexol on memory and psychomotor function in healthy volunteers
Authors: Quigley N. , Morgan D. , Idzikowski C. , King D.J.
Published: March 2007

Both antipsychotic and anticholinergic drugs have been implicated in the production of the memory deficits seen in schizophrenia. We compared the effects of chlorpromazine (50 mg) and benzhexol (5 mg) with placebo on a battery of tests of memory, psychomotor function and mood, in 12 healthy volunteers. Benzhexol, but not chlorpromazine, impaired both word recall and word recognition. Neither drug had an effect on long-term memory Both active compounds were associated with self-rated sedation, and chlorpromazine produced impairment in saccadic eye movements. This study supports the contention that sedation is unlikely to be the mechanism by which anticholinergic drugs exert their amnestic effect.
Enhanced GABAb receptor-mediated transmission in alcohol-dependence syndrome
Authors: Macdonald Shiona , Corrigan Frank M. , Gaskell David F. , French Michael
Published: March 2007

We have studied the GABAb receptor-mediated neurotransmissions of alcoholic patients by administering baclofen 10 mg orally and measuring the growth hormone (GH) response. There was a minimal GH response to the baclofen in one of eight control subjects and a greater GH response in 11 of the 16 alcoholic patients. There is thus evidence for increased transmission at the GABAb receptor in detoxified patients with alcohol-dependence syndrome.
Catecholamine regulation of the prefrontal cortex
Authors: Arnsten Amy F. T.
Published: March 2007

The catecholamines dopamine (DA) and norepinephrine provide an essential modulatory influence on the working memory and attentional functions of the prefrontal cortex (PFC). The following critique reviews evidence that (1) either insufficient or excessive DA D1 receptor stimulation is detrimental to PFC function, while DA stimulation of the D2 family of receptors may contribute to detrimental actions in PFC and (2) that norepinephrine has an important beneficial influence on PFC function through its actions at post-synaptic, α 2A adrenergic receptors, but impairs PFC function through actions at α 1 adrenergic receptors. Critical levels of catecholamine stimulation may be needed to optimize PFC cognitive function; high levels of catecholamine release during stress may serve to take the PFC 'off-line' to allow faster, more habitual responses mediated by the posterior and/or subcortical structures to regulate behavior. These studies have relevance to our understanding and treatment of disorders with prominent symptoms of PFC dysfunction.
Alertness and memory after sleep deprivation and diazepam intake
Authors: Gorissen M. , Tielemans M. , Coenen A.
Published: March 2007

Benzodiazepines (BZDs) give rise to memory impairments. It has been questioned whether or not these impairments are related to the drug's sedative, alertness-reducing effects. Therefore, in this study, alertness was reduced in healthy subjects both pharmacologically (15 mg diazepam) and non-pharmacologically (24-h sleep deprivation, SD) in order to assess whether these manipulations both gave rise to memory impairments. Twelve subjects were tested using a repeated measures cross-over design. Drug administration was placebo- controlled and double-blind. A subjective alertness reduction was established after diazepam intake and even more after SD. Additionally, performance-disruptive effects were found on psychomotor tasks after both SD and diazepam intake. However, only diazepam, and not SD, impaired delayed recall of a word list and recall of paired associates. Thus a reduction in alertness, i.e. sedation, cannot fully account for BZD-induced memory impairments.
A motivational learning hypothesis of the role of mesolimbic dopamine in compulsive drug use
Authors: Di Chiara Gaetano
Published: March 2007

The effects of drugs and substances of abuse on central dopamine (DA) transmission studied by in vivo monitoring techniques have been examined and compared with those of conventional reinforcers and in particular with food. The similarities and differences in the action of drugs and conventional reinforcers on DA transmission can provide the basis for an hypothesis of the mechanism of drug addiction and compulsive drug use. This hypothesis states that drug addiction is due to excessive control over behaviour exerted by drug- related stimuli as a result of abnormal motivational learning induced by repeated drug exposure. Such abnormal motivational learning would derive from the repetitive non-habituating property of drugs of abuse to activate DA transmission phasically in the nucleus accumbens (NAc) 'shell'. Thus, activation of DA transmission by conventional reinforcers is under strong inhibitory control by previous exposure to the reinforcer (habituation); this, however, is not the case with drug reinforcers. Repetitive, non-adaptive release of DA in the NAc 'shell' by drugs of abuse would result in abnormal strengthening of stimulus-reward (incentive learning) and stimulus-response associations (habit learning) that constitute the basis for craving and compulsive drug use.
Evidence that NMDA-dependent limbic neural plasticity in the right hemisphere mediates pharmacological stressor (FG-7142)-induced lasting increases in anxiety-like behavior
Authors: Adamec Robert E.
Published: March 2007

The hypothesis that N-methyl-D-aspartate (NMDA) receptors mediate initiation of lasting behavioral changes induced by the anxiogenic β-carboline, FG-7142, was supported in this study. Behavioral changes normally induced by FG-7142 were blocked when the competitive NMDA receptor blocker, 7-amino-phophono-heptanoic acid, was given prior to administration of FG-7142. When cats were subsequently given FG-7142 alone, the drug produced lasting behavioral changes like those reported previously. Flumazenil, a benzodiazepine receptor antagonist, reversed an increase in defensiveness produced by FG-7142 alone, replicating previous findings. The data are consistent with the hypothesis that NMDA-dependent long-term potentiation in limbic pathways subserving defensive response to threat mediates lasting increases in defensiveness produced by FG-7142.
GABAergic drugs and sexual behaviour in the rabbit: evidence for species-specific effects
Authors: Paredes Raúl G. , Contreras José Luis , Ågmo Anders
Published: March 2007

The effects of γ-amino butyric acid (GABA)-ergic drugs on male rabbit sexual behaviour have been evaluated. The GABAA agonist 4,5,6,7-tetrahydroxixazolo-5,4c-pyridin-3-ol (THIP), the GABAB agonist R-baclofen and the GABA antagonists picrotoxin and bicuculline were used. Injection of THIP, 20 mg/kg, s.c. produced a complete suppression of sexual behaviour and R-baclofen, 2.5 mg/kg, s.c. a significant inhibition. Intraperitoneal injections produced effects at higher doses than did s.c. injections. The inhibition produced by R-baclofen was associated with strong motor effects as shown by the water escape test. It is probable, therefore, that the reduced sexual behaviour observed after treatment with this drug is a consequence of sedative or muscle relaxant effects. By contrast, the dose of THIP that inhibited sexual behaviour had no effect on the water escape test. These results show that the GABA A agonist inhibits sexual behaviour in the male rabbit independent of effects on the motor system. The GABA antagonists had marginal or no effects on sexual behaviour. When these data are compared to previous results in the rat, substantial differences are seen. As there are differences between the effects on rat and rabbit sexual behaviour by other types of drugs, it appears that drug action on sexual behaviour cannot be generalized from one species to another.
Repeated administration of fluoxetine, desipramine and tranylcypromine increases dopamine D2-like but not D1-like receptor function in the rat
Authors: Ainsworth K. , Smith S.E. , Sharp T.
Published: March 2007

We tested the effect of repeated treatment (twice daily for 14 days) of rats with the antidepressant drugs fluoxetine, desipramine and tranylcypromine, on the behavioural response to the non-selective dopamine (DA) receptor agonist, apomorphine, the D 1-like receptor agonists, SKF 38393 and SKF 81297 and the D2-like receptor agonists, RU 24213 and quinpirole. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Fluoxetine, desipramine and tranylcypromine enhanced (albeit to a varying degree) the behavioural responses to apomorphine (0.75 mg/kg, s.c.), quinpirole (0.25 mg/kg, s.c.) and RU 24213 (0.75 mg/kg, s.c.). In contrast, fluoxetine, desipramine and tranylcypromine did not increase the behavioural responses to SKF 38393 (7.5 mg/kg, s.c.) and SKF 81297 (0.5 mg/kg, s.c.). Finally, fluoxetine, despiramine and tranylcypromine did not modify the behavioural responses to the concomitant administration of SKF 38393 (7.5 mg/kg, s.c.) and quinpirole (0.25 mg/kg, s.c.). Our data suggest that repeated administration of fluoxetine, desipramine and tranylcypromine increases central DA D2-like but not D1-like receptor function.
Effect of venlafaxine on pineal melatonin and noradrenaline in the male rat
Authors: Franklin M. , Clement E.M. , Campling G. , Cowen P.J.
Published: March 2007

Studies in vitro indicate that the antidepressant drug, venlafaxine (VEN), inhibits the reuptake of both serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NA) but has little activity on other neurotransmitter receptors. There are, however, few studies on the effects of VEN on monoamine neurotransmission in vivo. In the present study we examined the effect of VEN treatment on the melatonin content of the rat pineal gland because the synthesis of melatonin is regulated by the release of NA onto pinealocyte β-adrenoceptors. Acute treatment with higher doses (15 mg/kg) of VEN significantly increased pineal melatonin and NA but this effect was attenuated by subchronic treatment. These data are consistent with in vitro data suggesting that VEN increases NA neurotransmission at higher doses and that repeated treatment can desensitize pinealocyte β-adrenoceptors.
Medical Technology: Indicator of Modern Technocracy
Authors: Sassower Raphael
Published: March 2007

Technological innovations are commonplace today and usually provide great social benefits. The case of medical technology is of prime interest, for though it seems to provide primarily advantages, it may unwittingly turn over to technocrats the governance of modem society. This essay warns against the pitfalls of the age of technocracy, and calls for the maintenance of democratic controls over the development and implementation of modem technology.
Redefining Development Priorities: Genetic Diversity and Agroecodevelopment
Authors: Dahlberg Kenneth A.
Published: March 2007

Recent research on genetic and biological diversity suggests that they underlie, and are the source of renewable resources--which are themselves more fundamental than non-renewable resources. If this is the case, then our understandings of the "limits to growth" debate will need modification and current approaches to development--in both the industrial countries and in the Third World--will need reconceptualization. A major part of this will involve a reversal of roles and priorities for agricultural and industrial development. Also, more sustainable/regenerative types of agriculture and food systems will need to be developed. Current explorations along these lines are briefly reviewed. Finally, the links between this and the wider need to develop more sustainable societies are examined.
Optimal Strategies for the Diagnosis and Treatment of Coronary Artery Disease
Authors: Doubilet Peter , McNeil Barbara J. , Weinstein Milton C.
Published: March 2007

A computer program has been developed to aid in diagnostic and therapeutic decisions concerning a patient with chest pain. It provides an analysis tailored to the individual patient, in that the data used in the analysis depend on specific patient characteristics. The user can elect to examine all stored data values (probabilities, quality-adjusted life expectancies, and monetary costs), and to alter any of them. Decisions at three stages in the patient workup are considered: prior to any diagnostic test, following an exercise tolerance test, and following coronary angiography. The results of the analysis can be displayed in several tabular and graphical formats. In addition, the program can carry out a Monte Carlo simulation (or probabilistic sensitivity analysis) to determine the effect of uncertainty in the data on the stability of the choice of optimal strategy. (Med Decis Making 3:23-28, 1983)
Workup Bias in Prediction Research
Authors: Panzer Robert J. , Suchman Anthony L. , Griner Paul F.
Published: March 2007

Studies often suggest that accepted clinical predictors actually have little predictive strength. One explanation for some such results is the presence of workup bias. To explore the effects of workup bias in prediction research, the authors modeled the effects of workup bias on the ability of early clinical findings to predict intracerebral hemorrhage in patients with stroke. In a simulated biased sample, workup bias resulted in distorted operating characteristics for those clinical findings influencing application of the "gold standard" and for other related findings. Sensitivity was increased, but both specificity and likelihood ratios were decreased in the biased sample. Workup bias can spuriously decrease predictive abilities for accepted clinical findings when such findings guide application of the "gold standard." Investigators should be aware of the potential effects of workup bias, search for clues to its occurrence, and interpret study results carefully when it is present. Key words: workup bias; prediction rules; stroke; intracerebral hemorrhage. (Med Decis Making 7:115-119, 1987)
Solid Recommendations from Soft Numbers
Authors: Nease Robert F. , Bonduelle Yann
Published: March 2007

The authors review the probability threshold approach to test/treatment decisions developed by Pauker and Kassirer, 6,7 emphasizing that certain aspects of the nature of medical decisions call for a new approach. The utility threshold approach, while maintaining all the advantages of threshold methods in general, brings improvements. It diminishes the need to accurately assess one of the decision's parameters: the patient's utility for the outcome states. For a simple case of one disease with three outcome states (cured, diseased, dead) and one test, three utility thresholds are derived. The treat/no treat threshold, denoted by u*, separates the utility space in two. If the patient's value for the diseased state is greater than u*, the analyst can feel confident in recommending the patient forego treatment. Similar interpre tations are developed for u1, the no treatment/test utility threshold (the value u must take, given a positive test result, for the patient to be indifferent between foregoing and receiving treatment), and u2, the test/treatment utility threshold (the value u must take, given a negative test result, for the patient to be indifferent between foregoing and receiving treatment). Key words: medical decision analysis; threshold analysis; utility threshold. (Med Decis Making 7:220-233, 1987)
Laboratory Use
Authors: Schmitt Brian P. , Elstein Arthur S.
Published: March 2007

The quantitative principles of test selection and interpretation have been reluctantly integrated into clinical practice. This reluctance may reflect an underlying faculty attitude towards the laboratory. To evaluate this attitude, the scoring standards used for 23 patient management problems (PMPs) in the 1980 and 1983 Medical Knowledge Self-Assessment Programs were reviewed. All diagnostic options were categorized by dollar cost, risk, and a determination of "routineness." Attitudes were probed by reviewing the scores obtained by indiscriminate selection of all items in a category. Our analysis indicated that the examiners valued routine, little-ticket, little-risk items. Such selection would be rewarded 85% of the time and in 95%, no penalty would be received. Further, indifference was more frequent for little-ticket items and accounted for 11.7% of acceptable diagnostic expense. An examinee analyzing these scoring keys could reasonably conclude that routine, little-ticket items should be ordered whenever offered. Hence, at a national level, there is an attitude that implicitly encourages the use of these items in clinical practice. Key words: attitudes; diagnostic tests. (Med Decis Making 8:81-86, 1988)
A General Regression Methodology for ROC Curve Estimation
Authors: Tosteson Anna N. Angelos , Begg Colin B.
Published: March 2007

A method for applying generalized ordinal regression models to categorical rating data to estimate and analyze receiver operating characteristic (ROC) curves is presented. These models permit parsimonious adjustment of ROC curve parameters for relevant covariates through two regression equations that correspond to location and scale. Particular shapes of ROC curves are interpreted in relation to the kind of covariates included in the two regressions. The model is shown to be flexible because it is not restricted to the assumption of binormality that is commonly employed in smoothed ROC curve estimation, although the binormal model is one particular form of the more general model. The new method provides a mechanism for pinpointing the effect that interobserver variability has on the ROC curve. It also allows for the adjustment of ROC curves for temporal variation and case mix, and provides a way to assess the incremental diagnostic value of a test. The new methodology is recommended because it substantially improves the ability to assess diagnostic tests using ROC curves. Key words: ROC curves; ordinal regression; technology assessment; diagnostic tests. (Med Decis Making 8:204-215, 1988)
Threshold Analysis Using Diagnostic Tests with Multiple Results
Authors: Nease Robert F. , Owens Douglas K. , Sox Harold C.
Published: March 2007

Clinical problems represented by decision trees can be analyzed in terms of the probability threshold model, which provides management recommendations based on the prior prob ability of disease, the test threshold, and the test-treatment threshold. As originally proposed, the threshold model assumes that diagnostic tests provide information about a single event that is relevant to the decision. For some problems, however, a diagnostic test may provide information about more than one such event (e.g., a computed tomography [CT] scan gives information about both mediastinal and hilar metastases in lung cancer). The authors extend the probability threshold model to cases in which a single test provides information about two events that are relevant to the decision. They derive four thresholds that determine the best strategy for any combination of test results. The approach is illustrated for the decision to use a CT scan to stage lung cancer. The analysis reveals that: 1) the range of prior probabilities for which testing is optimal increases; 2) for some prior probabilities only test results about one event are important; 3) for some prior probabilities test results about both events are important; and 4) failure to account fully for information provided by a test can lead to erroneous test and treatment recommendations. Key words: decision theory; Bayes theorem; decision making, computer-assisted; decision support technics; predictive value of tests; lung neoplasms; probability threshold; decision analysis. (Med Decis Making 1989;9:91- 103)