bluuebunny/crossref_metadata_2025 huggingface dataset:
The Unesco Computerized Documentation System
Authors: Pobukovsky M.
Published: March 2007

In 1975, Unesco's Computerized Documenta tion System, (CDS) was combined with the Inte grated Set of Information Systems (ISIS) de veloped by the International Labour Organiza tion to create a comprehensive collection of programs for input, management and output in either batch or on-line mode, known as CDS/ ISIS. The same set of programs can be used to manipulate various data bases with different data content. Forty-three data bases are run by CDS/ISIS within the Unesco Secretariat and the package is made available free of charge to non-profit institutions in Member States. The system is being used to support an Integrated Documentation Network within Unesco and micro and minicomputer versions are soon to be released.
The Information Gap
Authors: Lundu Maurice C.
Published: March 2007

Analyses the origins of the myth of an information and knowledge gap between developed countries and those of sub-Saharan Africa and examines the present-day reality with regard to this gap.
Nuevas tecnologías y relaciones de produccion
Authors: Mostafa Solange Puntel
Published: March 2007

Discusses the relationship between new technologies and the socio-economic aspects of production and the implications for librarians, with special reference to Brazil.
The National Library of Sri Lanka and the national library system
Authors: Amarasiri M.S.U.
Published: March 2007

Outlines the historical background to the opening in 1990 of the National Library of Sri Lanka. Describes the activities of the Sri Lanka National Library Services Board and discusses its relationship with the new National Library. Outlines the main functions of the National Library, with particular emphasis on its role in promoting book development and general library development in Sri Lanka. Gives details of recently-formulated standards for school and public libraries. Describes library development projects at the provincial and regional ( Pradeshiya Sabha) levels, and the role of the library service in supporting the government's poverty alleviation programme ( Janasaviya).
Library consulting for national health systems
Authors: Weitzel Rolf
Published: March 2007

Increasing use is made of library consultants to advise the health authorities in the developing countries on improving information support to personnel employed in the national health system. The main problems encountered by consultants are structural as services must be provided to a widely dispersed user population. Intersectoral coordination should be exercised in order to obtain access to health-related information resources operating outside the administrative scope of the ministry of health. Financing is a critical aspect due to the multiplicity of potential funding sources. Technical aspects rank last and only two areas are discussed in some detail: collection development and bibliographic information retrieval. A comparison shows that the consultant working in a system context requires a whole range of specific qualities, skills and experiences in addition to those that compose the basic profile of the single-library consultant.
Developing higher education libraries in Papua New Guinea
Authors: Lee Hwa-Wei , Evans John
Published: March 2007

Summarizes the findings and recommendations of a 1991 survey of higher education libraries in Papua New Guinea. Six major libraries were identified as the major building blocks of a proposed Papua New Guinea Library and Information Network (PNGLINET). The situation of most other higher education libraries was very poor.
Clinical efficacy of paroxetine in resistant depression
Authors: Tyrer P. , Marsden C.A. , Casey Patricia , Seivewright N.
Published: March 2007

The antidepressant effects of a specific reuptake inhibitor of 5-hydroxytryptamine (5-HT), paroxetine, were tested in 24 patients with resistant depression who had failed to respond to conventional antidepressants after at least 4 weeks of treatment. A novel exper imental design was chosen in which all patients had 12 weeks of treatment beginning and ending with placebo therapy with 6 weeks of active drug treatment at some point in between. Ratings of depressive symptoms were made using the Hamilton rating scale (HRS) for depression, and the checklist for unwanted effects and their severity was also recorded before and during treatment at 2 week intervals. The change from placebo to active paroxetine therapy was made using a double-blind procedure. Patients who made a significant placebo response in the first 2 weeks of treatment were excluded from further analysis; 20 patients completed the study and satisfied all criteria for inclusion. Both groups of showed a significant improvement in symptoms after 4 weeks of paroxetine therapy. There were no significant treatment differences between the groups, but improvement in symptoms occurred sig nificantly later in the patients who had a longer period of initial placebo therapy. The experimental design also allowed study of withdrawal effects after stopping active treatment. There was no increase in adverse effects, including a subgroup associated with withdrawal problems, either during treatment with paroxetine or after the drug was stopped. The results suggest that paroxetine is probably an effective antidepressant, is well tolerated and has few adverse effects.
The effect of 5,7-DHT-induced lesions of the median raphe nucleus and chronic desipramine administration upon motor behaviour of rats given intrahippocampal clonidine injection
Authors: Płaznik Adam , Tamborska Ewa , Hauptmann Mirosława , Bidzinski Andrzej , Kostowski Wojciech
Published: March 2007

The role of serotonergic (5-HT) innervation of rat hippocampus in clonidine- induced behavioural effects was studied in naive and desipramine-pretreated animals. 5,7- DHT-lesions of the median raphe nucleus (MR) produced about 50 per cent decrease of serotonin and 5-hydroxyindoloacetic acid (5-HIAA) content in the rat cortex and hippocampus. Lesions of the MR also accelerated the attenuating effect of desipramine upon locomotor inhibition produced by intrahippocampal clonidine injections. In the forced swim test (FST) the MR lesion revealed the stimulatory potency of clonidine upon rat active behaviour, which was statistically significant. However, no further potentiation by MR lesions of DMI effects upon behavioural action of clonidine could be observed in this test. It is concluded that hippocampal serotonergic innervation plays a minor role in the antidepressant-induced changes in behavioural effects of clonidine, which probably occur via modulation of local alpha-adrenoceptors. It is also conceivable that the stimulatory effect of intrahippocampal clonidine injections in the forced swim test in MR-lesioned rats, may be due to the increase in the alpha-1-adrenoceptor function in this brain area.
Mediation by serotonin of the antiaversive effect of zimelidine and propranolol injected into the dorsal midbrain central grey
Authors: Audi E.A. , de Aguiar J.C. , Graeff F.G.
Published: March 2007

Previously reported results indicate that serotonin (5-HT) inhibits the neural sub strate of aversion in the dorsal midbrain central grey (DCG) of the rat. In addition, the present results show that microinjection of the 5-HT uptake inhibitor zimelidine (100 nmol) into the DCG of rats with chronically implanted chemitrodes raised the threshold of aversive electrical stimulation. This antiaversive effect of zimelidine was antagonized by pretreatment with the 5-HT2 receptor blocker ritanserin (10 nmol), also microinjected into the DCG. In contrast, the antiaversive effect of the benzodiazepine agonist midazolam (40 nmol) was unaffected by ritanserin. Propranolol (2.2, 4.4 and 8.8 nmol) raised the aversive threshold in a dose-depen dent way following its injection into the DCG. The antiaversive effect of 4.4 nmol of propranolol was antagonized by previous administration of ritanserin (10 nmol). Moreover, combined administration of zimelidine (100 nmol) followed by propranolol (4.4 nmol) caused an anti aversive effect which was equivalent to the sum of the effect of each drug alone. These results indicate that the antiaversive effect of intracerebrally injected zimelidine and propranolol is mediated by endogenous 5-HT, through activation of 5-HT2 receptors.
The 5-HT3 receptor antagonists ICS 205-930 and GR38032F, putative anxiolytic drugs, differ from diazepam in their pharmacological profile
Authors: Papp M. , Przegaliński E.
Published: March 2007

The pharmacological profile of the two 5-HT3 (5-hydroxytryptamine) receptor antagonists, the putative anxiolytics ICS 205-930 and GR38032F was compared with that of diazepam in four standard behavioural tests in rats. All the investigated drugs induced an anxiolytic effect in the passive avoidance test, having reduced the latency to re-enter the chamber previously associated with an inescapable footshock, and increased the time spent in that chamber. On the basis of the lowest effective dose, both ICS 205-930 and GR38032F were about 20 times more potent than diazepam, though the anxiolytic activity of either 5- HT3 receptor antagonist was confined to a narrow dose range (ICS 205-930: 93.7-187.5 μg/ kg, GR38032F: 125-375 μg/kg), their higher doses having been ineffective. The anxiolytic effect of diazepam, but not of ICS 205-930, was abolished by flumazenil. In contrast to diazepam, neither ICS 205-930 nor GR38032F—both given in doses up to 20 mg/kg—showed any activity in the pentylenetetrazol-induced seizures, open field, and rota-rod tests. These results suggest that the 5-HT3 receptor antagonists may represent a new class of anxiolytic drugs devoid of anticonvulsant, sedative or muscle-relaxant properties, and that their anxi olytic activity is not mediated by benzodiazepine receptors.
Increased slow wave sleep with 5-HT2 receptor antagonists: detection by ambulatory EEG recording and automatic sleep stage analysis
Authors: Solomon R.A. , Sharpley A.L. , Cowen P.J.
Published: March 2007

The effect on slow wave sleep (SWS) of 5-HT antagonists with different affinities for 5-HT1 and 5-HT2 receptors was investigated using ambulatory EEG monitoring in normal volunteers. The selective 5-HT 2 antagonists, ritanserin and cypropheptadine, increased SWS while the non-selective 5-HT antagonist metergoline did not. The histamine H 1-receptor antagonist, mepyramine, was similarly without effect on SWS. These findings suggest that home ambulatory monitoring with automatic sleep stage analysis may be useful in detecting the effect of selective 5-HT 2 receptor antagonists on SWS.
The discriminative stimulus effects of MK-801: Generalization to other N-methyl-D-aspartate receptor antagonists
Authors: Sanger D.J. , Zivkovic B.
Published: March 2007

Rats were trained to discriminate a dose of the NMDA antagonist MK-801 from saline using a standard, two-lever, operant procedure. The acquisition of this discrimination was rapid, rats reaching criterion performance in a mean of 32 sessions. The discriminative stimulus produced by MK-801 generalized to phencyclidine and (+)N-allylnormetazocine but only low levels of generalization were seen with (-)N-allylnormetazocine and with the anti- ischaemic drug ifenprodil and its derivative SL 82.0715. The MK-801 stimulus was partially antagonized by haloperidol. The results show that MK-801 can produce a discriminative stimulus which is shared by other non-competitive NMDA antagonists which have similar behavioural effects in other procedures. However, ifenprodil and SL 82.0715, which have also been shown to antagonize the effects of NMDA, do not produce similar behavioural effects or discriminative stimuli presumably because they act through a different site.
British Association for Psychopharmacology Max Hamilton Memorial Lecture Quantitative estimates of drug effects in psychopharmacology: what we measure and what we do not
Authors: Leber Paul
Published: March 2007

This paper is an edited version of the Max Hamilton Memorial Lecture that was delivered at the annual meeting of the British Association for Psychopharmacology in Cambridge in July 1989. In tribute to Professor Hamilton's pioneering efforts in the field, the lecture focuses on several aspects of the measurement process in psychopharmacology. The role of enumeration in the classification of psychopathology is reviewed and its importance illustrated with an example drawn from the literature. Attention is given to the fundamental link between agreements within the field about the nature and qualities of clinical phenomena and the field's ability to construct and use multi-item rating scales to measure meaningful changes in the intensity of psychopathology. The importance of global assessment as a validation procedure is emphasized and selected hazards to reliable inference are examined.
Effects of nicotine, oxotremorine and 9-amino 1,2,3,4- tetrahydroacridine (tacrine) on matching and non matching to position in rats: no evidence for mnemonic enhancement
Authors: Sahgal A. , Keith A.B. , Lloyd S.
Published: March 2007

Groups of rats were trained on one of two variants of an operant memory task which allows strength of memory (accuracy), bias and response rates to be measured directly. In matching to position (MTP), one of two retractable response levers appeared at random as the sample. A response caused the lever to retract and this was followed by a delay (0-64 s) interval, during which the rat had to approach, and respond at, the magazine tray. Both levers were then presented and the rat had to respond to the lever which had most recently appeared as the sample, for food reward. A second group of rats learned non-matching to position (NMTP). In this task, rats had to respond to the lever which had not appeared as the sample.

The subjects were then divided into subgroups and injected, peripherally and prior to test, with one of three cholinergic drugs. These were nicotine (NIC: 0-0.3 mg/kg), oxotremorine (OXO: 0-0.3 mg/kg) and 9-amino 1,2,3,4-tetrahydroacridine (tacrine, THA: 0-3.0 mg/kg). NIC had a delay-independent disruptive effect on accuracy, but only in the non-matching version, and it did not affect rate of responding. OXO and THA had no effect on accuracy, but adversely affected response latencies and rates.

The results suggest that these drugs do not affect memory mechanisms; instead, and at the doses used, certain types of bias may be induced (NIC) and general responsiveness altered (OXO and THA).
Identifying genes determining trait differences in behavior and drug response: a comment on 'Quantitative trait loci and psychopharmacology'
Authors: Goldman David , Filling-Katz Michele R.
Published: March 2007

In Plomin, McClearn and Gora-Maslak's target article (see also Science 248: 183-188, 1990), reverse genetic approaches are emphasized for locating genes determining behavioral and pharmacogenetic traits. Furthermore, prospects for such an undertaking are presented pessimistically in that behavioral traits are asserted to be polygenic (due to the simultaneous action of variant alleles at multiple loci) and are conceptualized as being determined in large part by unshared environmental factors. We disagree with Plomin et al. in three major areas and argue the following:

(1) Forward genetic approaches involving candidate locus analysis and detailed analysis of the phenotype are of primary importance for isolating genes for behavioral traits, as for other genetic traits.

(2) Virtually all physiologic processes and metabolic pathways involve sets of genes, resulting in genetic heterogeneity (multiple genetic origins for a trait). However, polygenicity is approximately as unusual for behavioral traits as for other traits.

(3) Heritability analyses underestimate the extent to which behavioral traits are amenable to genetic analysis and have been misinterpreted to overestimate the importance of environmental factors.
Comment on 5-HT and mechanisms of defence
Authors: Wetzler Scott , Asnis Gregory M. , van Praag Herman M.
Published: March 2007

The paper by Deakin and Graeff is a thought-provoking tour-de-force. They propose a comprehensive theory about serotonin (5-hydroxytryptamine; 5-HT) and anxiety, covering much of the same literature which we previously reviewed (Kahn et al., 1988a). We certainly agree that there seems to be an association between 5-HT function and anxiety, but we take issue with several important aspects of Deakin and Graeff's hypothesis. We limit our comments to their discussion of anxiety and panic.
Is lorazepam-induced amnesia specific to the type of memory or to the task used to assess it?
Authors: File Sandra E. , Sharma Rashmi , Shaffer Joe
Published: March 2007

Retrieval tasks can be classified along a continuum from conceptually driven (relying on the encoded meaning of the material) to data driven (relying on the perceptual record and surface features of the material). Since most explicit memory tests are conceptually driven and most implicit memory tests are data driven there has been considerable confounding of the memory system being assessed and the processing required by the retrieval task. The purpose of the present experiment was to investigate the effects of lorazepam on explicit memory, using both types of retrieval task. Lorazepam (2.5 mg) or matched placebo was administered to healthy volunteers and changes in subjective mood ratings and in performance in tests of memory were measured. Lorazepam made subjects significantly more drowsy, feeble, clumsy, muzzy, lethargic and mentally slow. Lorazepam significantly impaired recognition memory for slides, impaired the number of words remembered when the retrieval was cued by the first two letters and reduced the number of pictures remembered when retention was cued with picture fragments. Thus episodic memory was impaired whether the task used was conceptually driven (as in slide recognition) or data driven, as in the other two tasks. Analyses of covariance indicated that the memory impairments were independent of increased sedation, as assessed by self-ratings. In contrast to the deficits in episodic memory, there were no lorazepam-induced impairments in tests of semantic memory, whether this was measured in the conceptually driven task of category generation or in the data-driven task of wordstem completion.
Valproate effects on pre-optic GABA release and pituitary LH secretion in the rat
Authors: Wolf Rainer , Tscherne Ursula , Emrich Hinderk M.
Published: March 2007

The in vivo effects of the anticonvulsant drug sodium valproate (VPA) on pre-optic gamma-aminobutyric acid (GABA) release and pituitary luteinizing hormone (LH) secretion were studied by perfusing the pre-optic area of unanaesthetized, freely moving ovarectomized rats through push-pull cannulae at a flow-rate of 20 >μl/min with a fraction period of 15 min. Local treatment with 40, 100, 400 and 1600 μg VPA/ml differently affected pre-optic GABA release and pituitary LH secretion concerning mean level, mean pulse amplitude and mean pulse frequency. GABA levels in perfusate were suppressed by local treatment with 40 and 100 μg VPA/ml CSF, respectively, whereas no significant change could be observed at the highest concentration used (1600 μg VPA/ml CSF). Pituitary LH secretion was reduced by pre-optic perfusion with 100 μg VPA/ml CSF with regard to mean plasma level and pulse amplitude but no significant change in pulse frequency could be observed. By raising VPA concentration the effects became more pronounced, and at 1600 μ g VPA/ml CSF there was a marked reduction of LH secretion regarding mean plasma level, amplitude and frequency. In conclusion, the present data put forward our view that the mechanism of action of VPA generates an enhancement of GABAergic transmission different from that involving elevated extracellular GABA.
Unaltered number of brain serotonin uptake sites in suicide victims
Authors: Andersson Anna , Eriksson Anders , Marcusson Jan
Published: March 2007

The 5-HT uptake sites were studied with [3H ] paroxetine as radioligand in frontal cortex, cingulate cortex and hypothalamus from a control group (n=22) and a group of suicide victims (n = 19). The binding was also analysed with regard to the method of suicide (violent or non-violent) and history of depressive symptoms. The apparent dissociation constant (Kd ) was the same, 0.07-0.10 nM, and did not differ between the two groups studied. The maximum number of binding sites ( Bmax) for the controls were frontal cortex 112±21, cingulate gyrus 227±92 and hypothalamus 699±240 fmol/mg protein. The Bmax values for the suicide group were not different from those of the control group. When the binding parameters were analysed according to the method of suicide (violent or non-violent) there were no differences in comparison to the control group or between these two suicide groups. Similarly, suicides with and without history of depression did not differ in [3H ] paroxetine binding and were not different from the control group. The control and suicide groups were not different with respect to age and post- mortem storage time. Considering 5-HT uptake sites as indirect markers for 5-HT terminals, these data suggest that the 5-HT terminal system is intact in the neocortex, the limbic system and in the hypothalamus in suicide victims.
Effect of D-1 or D-2 receptor stimulation on memory retrieval in mice
Authors: Zarrindast M.R. , Sattari-Naeini M. , Motamedi F.
Published: March 2007

Mice were trained in one-way active avoidance procedure and retention was tested at 4, 8, 16 and 24 h after training of animals and compared with non-shocked or untrained animals. The effect of drugs was tested on retrieval 24 h after training in other groups of mice. High doses of apomorphine or bromocriptine impaired, while low doses of the drugs improved, retrieval of avoidance. High doses of sulpiride reversed the impairment induced by high doses of these dopamine agonists. Low doses of sulpiride antagonized the improvement of retrieval induced by low doses of apomorphine. SKF 38393 treatment of animals also improved the retrieval. The retrieval impairment induced by higher doses of apomorphine or the improvement induced by different doses of SKF 38393 was antagonized by SCH 23390 pre-treatment. Single administration of SCH 23390 or low doses of sulpiride also impaired retrieval. It is concluded that stimulating post-synaptic D-2 dopamine receptors impairs retrieval whilst activation of pre-synaptic D-2 or post-synaptic D-1 receptors improves memory retrieval.
Optimizing treatment for the elderly depressive: new antidepressants in the elderly
Authors: Katona C.
Published: March 2007

This paper considers how to optimize the treatment of elderly depressed patients, in the particular context of the use of relatively new antidepressant drugs.
Co-existence of panic disorder and sleep paralysis
Authors: Allen Danny , Nutt David
Published: March 2007

Sleep paralysis is a clinical phenomenon that is often a feature of narcolepsy. As its co-existence with panic disorder has not been noted before, we report on two cases in which the two conditions co-exist and postulate a neurochemical mechanism.
The unique effect of methiothepin on the terminal serotonin autoreceptor in the rat hypothalamus could be an example of inverse agonism
Authors: Moret Chantal , Briley Mike
Published: March 2007

Slices of rat hypothalamus were pre-incubated with [3H] 5-hydroxytryptamine ([3H ] 5-HT), then superfused continuously and twice stimulated electrically. The effects of methiothepin, metergoline and alprenolol, all considered to be terminal 5-HT autoreceptor antagonists (although they also act at a number of other receptors), were studied. The stimulation-evoked overflow of tritium was increased by methiothepin in a concentration- dependent manner. The slight enhancing effect of alprenolol was not concentration dependent and metergoline, at concentrations which did not modify spontaneous outflow, was devoid of effect on evoked tritium overflow. The concentration-dependent inhibition by the terminal 5-HT autoreceptor agonist, lysergic acid diethylamide (LSD), of the electrically induced release of [3H] 5-HT was antagonized by methiothepin, alprenolol and metergoline. The stimulatory effect of methiothepin on tritium release was diminished by metergoline and by alprenolol at a concentration which slightly enhanced the evoked overflow of [3H ] 5-HT when given alone. Thus methiothepin induced an effect opposite to that of an agonist, in contrast to alprenolol and metergoline which under our conditions had no effect by themselves but reduced the effect of an agonist. In addition, the stimulating effect of methiothepin on release was reversed by two terminal 5-HT autoreceptor antagonists, alprenolol and metergoline. These results are consistent with methiothepin being an inverse agonist at the terminal 5-HT autoreceptor.
Clonidine-induced changes in the spectral distribution of heart rate variability correlate with performance on a test of sustained attention
Authors: Middleton H.C. , Coull J.T. , Sahakian B.J. , Robbins T.W.
Published: March 2007

Conventional measures of cardiovascular activity correlate poorly with psychological variables and therefore provide imperfect physiological indices of arousal. We have investigated the effects of clonidine upon the spectral distribution of heart rate variability and upon performance on a test of sustained attention. Our findings suggest that activity of the central noradrenergic system influences the distribution of heart rate variability in the ~ 0.1 Hz range. Furthermore, the finding of a strong correlation between the effects of clonidine upon each of these variables supports the use of spectral analysis of heart rate variability in the study of arousal.
Stimulation of central 5-HT1D receptors causes hypothermia in the guinea-pig
Authors: Skingle M. , Higgins G.A. , Feniuk W.
Published: March 2007

The 5-HT1 receptor agonist GR46611 (3-30 mg/kg s.c.) caused a dose-related decrease in rectal temperature in the adult guinea-pig. A lower dose (20 μg) administered directly into the lateral cerebral ventricle also caused a hypothermic response, suggesting that this effect is centrally mediated. GR46611-induced (10 mg/kg s.c.) hypothermia was not attenuated by WAY100135 (3-10 mg/kg s.c.), ritanserin (0.3-1 mg/kg s.c.), spiperone (0.1-0.3 mg/kg s.c.) and ondansetron (0.1-1 mg/kg s.c.), suggesting that 5-HT1A, 5-HT2A, 5-HT 2C and 5-HT3 receptors are unlikely to be involved in this response. In contrast, the poorly selective 5-HT receptor antagonist, metergoline (1-10 mg/kg s.c.), and the potent 5-HT1D receptor antagonist, GR127935 (0.1-1 mg/kg p.o.), antagonized the effects of GR46611. The present data suggest that antagonism of GR46611-induced hypothermia may be useful for assessing the potency and duration of action of centrally-acting 5-HT 1D receptor antagonists in the guinea-pig.
Cholinergic blockade and human information processing: are we asking the right questions?
Authors: Rusted Jennifer
Published: March 2007

This paper reviews the literature on the effect of cholinergic blockade on human information processing, within the context of current debate concerning the relationship between deficits in attention and memory tasks. It questions whether we are making the most of the tools available to us and the opportunities there are to explore not only the neurochemical correlates of psychological function, but also the cognitive models on which the psychopharmacological research feeds. Current theoretical issues within cognitive psychology are discussed, and the drug studies are re-evaluated in terms of the resource model of information processing, which focuses on issues of automaticity of processes, and resource availability, rather than modular dissociations between attention and memory.
5-HT 2C receptor sensitivity during treatment with selective serotonin re-uptake inhibitors
Authors: Williams R. , Sharpley A.L. , Cowen P.J.
Published: March 2007

We studied the effect of repeated treatment with selective serotonin re-uptake inhibitors (SSRIs) on the sensitivity of brain 5-HT2C receptors, by measuring the decrease in slow wave sleep (SWS) that follows administration of meta-chlorophenylpiperazine ( mCPP) (7.5 mg orally). mCPP significantly lowered SWS both in patients taking SSRIs and in a group of healthy controls. There was, however, no difference in the response between the two groups. The results do not support the suggestion that repeated SSRI treatment alters the sensitivity of 5-HT2C receptors in the human brain. The present study, however, cannot exclude the possibility that a decrease in 5-HT2C receptor sensitivity was offset by higher plasma levels of mCPP in the SSRI-treated group.
A double-blind comparison of sertraline and clomipramine in the treatment of major depressive disorder and associated anxiety in general practice
Authors: Moon C.A.L. , Jago W. , Wood K. , Doogan D.P.
Published: March 2007

In this double-blind study in primary care patients, the efficacy and safety of sertraline, an antidepressant which is a selective inhibitor of serotonin re-uptake, was compared with clomipramine. Patients with DSM-III-defined major depression and with significant anxiety randomly received 50-150 mg of either sertraline (N=51) or clomipramine (N=55) once daily for 6 weeks. The mean final daily dose was 63.5 mg sertraline and 60.6 mg clomipramine. Seventy five percent of sertraline-treated and 79% of clomipramine-treated patients were maintained on the lowest dose of 50 mg once daily. The mean scores of all the rating scales (HAM-D, HAM-A, HAD, CGI) showed similar efficacy between the treatments in reducing the symptoms of depression and anxiety. Clomipramine was less well tolerated than sertraline with a greater overall incidence of side effects, or significantly greater incidence of anticholinergic side effects and significantly more patient withdrawals due to side effects; 18% in the clomipramine group compared with 4% in the sertraline group. The results indicate that sertraline is an effective agent to use in primary care patients with depression and associated symptoms of anxiety and is better tolerated than the tricyclic comparator clomipramine.
Differential changes in glutamate receptor subunit messenger RNAs in rat brain after haloperidol treatment
Authors: Eastwood Sharon L. , Story Pippa , Burnet Philip W. J. , Heath Paul , Harrison Paul J.
Published: March 2007

Glutamate receptors are implicated in several neuropsychiatric disorders and in the actions of neuroleptic drugs used to treat them. To help clarify how these drugs impinge upon the glutamatergic system, we have studied the effects of 2 weeks' haloperidol (2 mg kg-1 d-1) upon the distribution and abundance of glutamate receptor mRNAs in rat brain. The mRNAs detected were those encoding the glutamate-binding protein (GBP), the N-methyl D-aspartate (NMDA) receptor (NR1 subunit) and the flip and flop isoforms of α-amino-3-hydroxy- 5-methyl-4-isoxazolpropionate (AMPA)-preferring non-NMDA receptors gluR1 and gluR2. The mRNAs were studied using in situ hybridization histochemistry in dorsolateral striatum, nucleus accumbens, frontal cortex and hippocampus. Haloperidol led to an increase in GBP mRNA in striatum and frontal cortex but not in hippocampus. AMPA receptor mRNAs showed gene- and isoform-specific alterations in treated animals, with a significant increase in the proportion of gluR2 flip compared to gluR2 flop. The gluR1 flop:gluR2 flop ratio also increased. No differences were observed for NR1 mRNA in any area. Thus, subchronic administration of haloperidol has a molecularly and spatially specific effect upon expression of glutamate receptor-related transcripts. The data have several implications. Firstly, the enhanced expression of GBP mRNA may contribute to the alterations in other glutamatergic parameters observed after neuroleptics. Secondly, the pattern of changes for the NMDA and AMPA receptor mRNAs suggests that the alterations in density of these receptors and their mRNAs reported in schizophrenia are not an artefact of neuroleptic treatment. Finally, the specific increase in flip:flop mRNA ratio for gluR2, together with the increased proportion of gluR1 flop:gluR2 flop mRNA, is likely to affect the properties of the encoded AMPA receptors. Such changes may be relevant to the desired or undesired effects of these drugs.
Atypical antipsychotic drugs in the treatment of manic syndromes in patients with HIV-1 infection
Authors: Scurlock Hilary J. , Singh Ashok N. , Catalan Jose
Published: March 2007

We report four people with human immunodeficiency virus (HIV) infection and mania whose manic symptoms improved when given the atypical antipsychotic agent remoxipride as an adjunct, and in whom traditional neuroleptics were not well tolerated due to marked extrapyramidal side effects. General issues surrounding choice of pharmacological agent in HIV-related mania are discussed.
5-HT 1D receptors mediate SKF 99101H-induced hypothermia in the guinea pig
Authors: Hatcher J.P. , Slade P.D. , Roberts C. , Hagan J.J.
Published: March 2007

The selective, brain penetrant, 5-HT1D receptor agonist SKF 99101H (10-30 mg/kg i.p.) caused a dose-related fall in rectal temperature in guinea pigs which lasted longer than 2 h. Sumatriptan (1.0-100 mg/kg i.p.), a selective 5-HT1D agonist which does not penetrate the brain, did not produce hypothermia, suggesting that peripheral mechanisms are not critically involved in the response. The hypothermia induced by SKF 99101H (30 mg/kg i.p.) was dose-dependently blocked by the 5-HT1D receptor antagonists GR 127935 (0.01-1 mg/kg i.p.) and GR 125743 (0.01-3 mg/kg i.p.), confirming the role of 5-HT1D receptors. Mianserin (0.3-10.0 mg/kg i.p.) and granisetron (0.1-3.0 mg/kg i.p.) were inactive, suggesting that 5-HT2A/2B/2C or 5-HT 3 receptors play no significant role in the generation of the hypothermic response. Nor was the hypothermia reversed by prazosin (0.03-1.0 mg/kg i.p.), idazoxan (0.03-1.0 mg/kg i.p.) or scopolamine (0.01-0.3 mg/kg i.p.), thereby excluding mediation by α1- and α2-adrenoceptors and muscarinic receptors. WAY 100635 (0.1-1.0 mg/kg) significantly potentiated the effect of SKF 99101H. The antagonists, when given alone, had no effect on body temperature, with the exception of prazosin (0.1 and 1.0 mg/kg). Three days of treatment with parachloroamphetamine (30 mg/kg i.p.) depleted forebrain 5-HT by ∼ 75% in frontal cortex, hypothalamus, hippocampus and striatum, but failed to alter the hypothermic response to SKF 99101H. The hypothermia is, therefore, unlikely to be mediated by 5-HT1D receptors located on 5-HT neurons. SKF 99101H-induced hypothermia in the guinea pig may serve as a useful model for investigation of centrally acting 5-HT 1D receptor antagonists.
Lorazepam 0.25 mg twice a day improves aspects of psychometric performance in healthy volunteers
Authors: Bourin Michel , Colombel Marie-Claude , Malinge Myriam
Published: March 2007

The effects of lorazepam (0.25 mg) twice a day on several cognitive and performance tasks, pictures test, digit-symbol substitution test (DSST), choice reaction time (CRT) and critical flicker fusion (CFF), were investigated in healthy students. A double-blind independent group design was used to compare placebo and lorazepam (30 volunteers in each group). After randomisation, all subjects received placebo for 3 days (D), followed by 14 days of treatment, with either lorazepam or placebo. Subjects completed a battery of tests at Do, then D3, D7 , D10 and D14. D3 performance was poorer in the lorazepam group except for CFF (ascending values and total values), yet the only significant improvement was in total reaction time on the CRT test. However, a significant improvement of performance was shown at D7, D10 and D14 in the lorazepam group compared with the control group (except in recognition reaction time). The current study shows that low repeated doses of lorazepam are able to produce small improvements in some aspects of psychomotor and cognitive functions in healthy volunteers. Different points are discussed to explain the performance improvement: training effect, tolerance effect, partial inverse agonist effect and the possible release of cholecystokinin.
Neurochemical and some related psychopharmacological aspects of Tourette's syndrome: an update
Authors: Baker G.B. , Chokka P.R. , Bornstein R.A.
Published: March 2007

Neurochemical investigations of Tourette's syndrome (TS) suggest that the symptoms of this disorder may be the result of an imbalance among several neurotransmitter and/or neuromodulator systems. Neurochemicals which have been studied included: catecholamines; acetylcholine; tryptophan and its metabolites; the amino acids γ-aminobutyric acid (GABA), glutamate, phenylalanine and p-tyrosine; trace amines; opioid peptides; cyclic AMP and androgenic hormones. A suitable animal model of TS would do much to advance our understanding of this disorder, and there are some interesting recent developments in this regard.
Bupropion and sertraline combination treatment in refractory depression
Authors: Marshall Randall D. , Johannet Christopher M. , Collins Pamela Y. , Smith Helen , Kahn David A. , Douglas Carolyn J.
Published: March 2007

A sizeable minority of depressed patients, estimated at 15-20%, suffer chronic symptoms which often persist despite appropriate treatment. The search for new, more efficacious pharmacotherapies has included testing existing medications for additional therapeutic effects, such as in combination treatment. Four treatment- refractory patients who presented to the authors for clinical care are described, in which the combination of bupropion and sertraline was effective for a major depressive episode. None of the patients experienced adverse effects. Two carried the diagnosis of unipolar depression, and two, bipolar disorder. All had prior adequate, but ineffective, separate trials of buproprion and a selective serotonin re-uptake inhibitor (SSRI), including sertraline. All had chronic depression with multiple failed medication treatments, arguing against the alternative explanation that their improvement represented a placebo response or spontaneous remission. The efficacious combination of sertraline and bupropion may be due to synergism of its two distinct antidepressant mechanisms involving serotonergic, dopaminergic and noradrenergic systems.
Central benzodiazepine receptor imaging and quantitation with single photon emission computerised tomography: SPECT
Authors: Okocha Chike I. , Kapczinski Flavio , Lassen Niels , Lader Malcolm H.
Published: March 2007

This review discusses the current use of single photon emission computerised tomography (SPECT) for central benzodiazepine receptor imaging and quantitation. The general principles underlying SPECT imaging and receptor quantitation methods such as the kinetic, pseudo-equilibrium and steady-state (tracer infusion and bolus) approaches are described. The advantages and practical drawbacks of these techniques are highlighted.
Compressed opiate withdrawal syndrome and naltrexone
Authors: Farrell Michael , Strang John
Published: March 2007

The oral opiate antagonist naltrexone is in regular use in clinical practice with abstinent opiate-dependent individuals. Acute opioid withdrawal is a well-recognised consequence of consuming naltrexone while opiate dependent. Two cases of naltrexone-induced opiate withdrawal are reported. The compressed nature of the withdrawal syndrome in both of these cases and the implications for the management of protracted withdrawal symptoms are discussed. The theoretical implications of this experimental and clinical phenomenon are reviewed.
Regional differences in the effect of haloperidol and atypical neuroleptics on interstitial levels of DOPAC in the rat forebrain: an in vivo microdialysis study
Authors: Fink-Jensen Anders , Hansen Liselotte , Hansen John Bondo , Nielsen Erik B.
Published: March 2007

The effect of 'typical' and 'atypical' neuroleptics on interstitial levels of the dopamine metabolite 3,4- dihydroxyphenylacetic acid ([DOPAC]e) in the dorsolateral striatum (DLSt), the nucleus accumbens (NAc) and the medial prefrontal cortex (PFC) was investigated in awake rats by use of the microdialysis technique. All neuroleptics increased [DOPAC]e in the DLSt, NAc and in PFC. However, the 'atypical' neuroleptics clozapine, risperidone, sertindole and NNC 22-0031 showed an apparent cortical selectivity by preferentially elevating [DOPAC]e in the PFC compared with the DLSt and NAc, a feature which was not observed with the 'typical' neuroleptic haloperidol. Our data suggest that 'atypical' neuroleptics can be differentiated from the 'typical' neuroleptic, haloperidol, with respect to their ability to increase [DOPAC]e in PFC relative to DLSt and NAc.
A double-blind, placebo-controlled study of tacrine in patients with Alzheimer's disease using SPET
Authors: Prentice Neil , Van Beck Margaret , Dougall Nadine J. , Moffoot Anthony P. R. , O'Carroll Ronan E. , Goodwin Guy M. , Ebmeier Klaus P.
Published: March 2007

Background: the effect of single-dose and long-term cholinergic enhancement with tacrine on regional cerebral perfusion was examined in patients with Alzheimer's disease using single-photon emission tomography (SPET). Method: 23 patients with probable Alzheimer's disease (DSM-III-R and NINCDS-ADRDA criteria) were scanned before and after a single oral dose of tacrine at the start of the study and again after 12 weeks of randomized, double-blind treatment with tacrine or placebo, using high resolution 99mTc-Exametazime SPET. Patients also underwent neuropsychological testing with the CAMCOG, the Mini-Mental State Examination and the Rivermead Behavioural Memory Test before and after 12 weeks of treatment. Results: occipital count ratios in all regions of interest declined by 3% over 12 weeks, indicating a progression of the disease. Acute tacrine challenge resulted in a 16% increase in the superior frontal and a 11% decrease in the anterior temporal cortex. The acute effects of tacrine were modified by 12 weeks of treatment, particularly in the medial frontal (cingulate) cortex where active treatment was associated with a reduced acute tacrine response. There were no changes in cognitive function associated with active treatment. Conclusion: the study demonstrates the sensitivity of cerebral perfusion measures to changes during acute and medium-term tacrine treatment.
Ritanserin facilitates anxiety in a simulated public-speaking paradigm
Authors: Guimarães F.S. , Mbaya P.S. , Deakin J.F.W.
Published: March 2007

The effects of ritanserin, a 5-HT2A/2C (5-hydroxytryptamine) antagonist, have been investigated in simulated public speaking with healthy volunteers. The aim was to investigate the role of 5-HT in subjective experimental anxiety. There were three experimental groups each comprising four or five males and 11 females. Subjects received placebo, ritanserin 2.5 or 10 mg, p.o. They rated themselves using the Spielberger State-Trait Anxiety Inventory and visual analogue scales factored into anxiety, sedation and discontentment scores. Autonomic measures included skin conductance and heart rate. Subjects were told, 75 min after drug or placebo ingestion, without prior warning, to prepare a 4-min speech. Measures were taken before, during and after the speech. Ritanserin prolonged the anxiety induced by the procedure on the subjective ratings but had minimal effect on autonomic responses to the procedure. The result contrasts with an anxiolytic-like effect of ritanserin on aversively conditioned autonomic responses. The present finding is compatible with animal behavioural evidence that 5-HT has distinct and opposing roles in modulating conditioned and unconditioned anxiety.
Pindolol augmentation of sertraline in resistant depression and its effect on sleep
Authors: Bell Caroline , Wilson Susan , Nutt David J.
Published: March 2007

A case is reported of a 34-year-old lady with a 2-year history of resistant depression who responded to pindolol augmentation of sertraline. It also illustrates the use of sleep electroencephalogram measures as a way of assessing changes in brain 5-hydroxytryptamine function.
Mood improvement in 'normal' volunteers
Authors: Gorenstein Clarice , Gentil Valentim , Melo Marcio , Lotufo-Neto Francisco , Lauriano Valéria
Published: March 2007

To test the hypothesis that clomipramine is effective in improving subthreshold non-specific symptoms in subjects without any established psychopathology, we conducted a double-blind, cross-over controlled trial of clomipramine (oral doses of 10-40 mg/day) and propanteline (active placebo) for 5 weeks in nine normal volunteers. Four other subjects completed the first part of the trial. These subjects were selected from 275 respondents to newspaper and radio requests for subjects who considered themselves as normal but were unhappy about their usual moods. They did not reach cut-off scores in the Self-Report Questionnaire and did not meet diagnostic criteria for any lifetime or current ICD-10 or DSM-III-R condition, as assessed by an open psychiatric interview and the Schedules for Clinical Assessment in Neuropsychiatry. Despite the small sample and the low level of initial symptomatology, both subjects and observers consistently detected significant improvements with clomipramine in a number of assessments of mood, notably decreased irritability and anxiety. This controlled trial suggests that it is possible to improve subclinical complaints through psychopharmacological agents, raises questions about the mechanisms of their action and discusses their implications.
Attitudes Toward Quality of Survival
Authors: Sutherland Heather J. , Llewellyn-Thomas Hilary , Boyd Norman F. , Till James E.
Published: March 2007

The purpose of this study was to examine attitudes toward the duration of survival in different health states. Health professionals were asked to consider hypothetical situ ations in which a specified period of time would be spent in a defined health state. Preferences for these different situations were assessed using two methods—a Pref erence Questionnaire and a Certainty Equivalence method. The results obtained indicated that attitudes toward duration of survival depended strongly on the amount of time to be spent in a hypothetical health state, and on the quality of the state. As the duration of survival increased, or the state under consideration became more dysfunctional, a higher proportion of raters expressed a preference for imme diate death over further survival in the dysfunctional state. These results contradict the view that time preference curves always increase monotonically, independent of the quality of survival. Instead, subjects appeared to identify a variable, the "maxi mal endurable time" in a given state. When this time was exceeded, attitudes toward additional increments of survival changed dramatically. (Med Decis Making 2:299-309, 1982)
A Mathematical Approach to Interpretation and Selection of Diagnostic Tests
Authors: Doubilet Peter
Published: March 2007

When the presence of a specific disease is being considered, a diagnostic test can often help the physician to choose between subjecting the patient to an extensive workup (or treatment) and proceeding no further. Decisions concerning the use of a test require that three judgments be made: (1) Should the test be done? (2) Which test (if any) should be used if two or more are available? (3) If a test that can take on more than two values is performed, what is the correct cutoff point (or positivity cri terion) that determines whether or not to proceed? This paper presents a mathemati cal technique to answer these questions, taking into account data concerning the patient (summarized as the prior, or pre-test, probability of disease), the test, and the workup (or treatment). The technique is presented in a graphical form that can be applied to any clinical situation in which the needed data are available. (Med Decis Making 3:177-195, 1983)