bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroleptic discontinuation in the very stable schizophrenic patient: Relapse rates and serum neuroleptic levels
Authors: Sampath G. , Shah A. , Krska J. , Soni S. D.
Published: December 2004

This double‐blind, placebo‐controlled study investigated the effect of discontinuation of maintenance neuroleptic medication in chronic, long‐stay schizophrenic patients who had been clinically stable for over 5 years. After 12 months, 75 per cent of the patients on placebo had relapsed as compared to 33 per cent on active medication and relapses in the placebo group occurred significantly earlier during the study; survival analysis revealed the differences to be statistically significant. No clear predictors of relapse could be identified, although patients who relapsed from either group were more likely to have had higher scores for anxiety symptoms and a lower serum prolactin level at baseline. It was concluded that even in older patients who have been chronically ill with prominent negative symptoms and living in a relatively undemanding environment on stable doses of neuroleptics, the risk of relapse remains unacceptably high after abrupt withdrawal of maintenance neuroleptic therapy.
Assessment of magnitude and availability of a non‐drug reinforcer on preference for a drug reinforcer
Authors: Zacny J. P. , Divane W. T. , de Wit H.
Published: December 2004

This study examined choice of beer over an alternative, non‐drug reinforcer (food or money), under conditions where the magnitude and availability of the non‐drug reinforcer was varied. Normal volunteers participated in three sessions consisting of a computerized choice task followed by a period of relaxation and consumption of earned reinforcers. The computer task consisted of a concurrent choice schedule in which the availability of the non‐drug reinforcer was varied across ‘trials’ from random ratio 1.3 to 16 (probability of reinforcement: 75 per cent to 6 per cent). Across the three sessions the magnitude of the non‐drug reinforcer was varied (i.e. small, medium, large). The magnitude and availability of beer remained constant across trials at a random ratio 4 (probability of reinforcement: 25 per cent). Two experiments were conducted, one in which food was the alternative reinforcer (Experiment I) and one in which money was the alternative reinforcer (Experiment II). In both experiments, decreasing the response requirement for the non‐drug reinforcer within the sessions resulted in an orderly decrease in the amount of responding to obtain alcohol. In Experiment I, changes in the magnitude of the food reinforcer did not change responding for beer. In Experiment II, however, responding for beer decreased when the magnitude of the alternative monetary reinforcer was increased. Thus, changes in the magnitude of an alternative reinforcer may have differential effects on responding for a drug reinforcer, depending on the nature of the alternative reinforcer.
5HT‐2 receptor and fluvoxamine effect in obsessive‐compulsive disorder
Authors: Erzegovesi Stefano , Ronchi Paolo , Smeraldi Enrico
Published: December 2004

The aim of the study was to test the role of the 5HT‐2 receptor in the antiobsessional effect of 5HT uptake inhibitors. For this purpose we designed a double blind controlled clinical trial, in which ritanserin (a specific 5HT‐2 receptor antagonist) or placebo were administered to a sample of 10 patients affected by Obsessive Compulsive Disorder (OCD), symptomatologically stabilized during fluvoxamine monotherapy. In order to quantify OCD symptom severity we used the Yale Brown Obsessive Compulsive Scale (Y‐BOCS), administered weekly for the 14 days of the study. One way Analysis of Variance (ANOVA), performed on Y‐BOCS total scores, showed a significant difference between the two treatment groups. The difference between ritanserin and placebo effect seemed to be related either to the slight worsening of the ritanserin group, or to the improvement in the placebo one. These results suggest that 5HT‐2 receptor may be involved in the antiobsessional effect of fluvoxamine.
Testing the effects of the imidazopyridine zolpidem on memory: An ecologically valid approach
Authors: Jackson J. L. , Louwerens J. W. , Cnossen F. , de Jong H. T. P.
Published: December 2004

The present study explores whether memory impairments are found on the morning following intake of the hypnotic zolpidem which is a member of a new pharmaceutical class, the imidazopyridines. The procedure used is novel: it involves testing subjects in their own homes via the telephone. A previous study using this technique found significant deficits in performance on the morning following intake of the benzodiazepines, flunitrazepam and midazolam, on tasks which load heavily on both the speed and capacity aspects of the human information processing system. Using the same tests, results from the present study fail to find any significant effects on the morning following zolpidem intake.
Rapid lithiumization in acute manic patients
Authors: Moscovich D. G. , Shapira B. , Lerer B. , Belmaker R. H.
Published: December 2004

Nine patients with acute mania were treated with high‐dose lithium therapy and daily blood level monitoring for the first 3 days of treatment. Rapid reduction in psychopathology was seen. It is possible that the delay of 7–10 days in clinical response to usual lithium treatment may be partially pharmacokinetic, and that high‐dose lithium loading at the onset of treatment of mania may reduce the need for neuroleptic co‐treatment.
Comparison of clomipramine, alprazolam and placebo in the treatment of obsessive—compulsive disorder
Authors: Stein D. J. , Hollander E. , Mullen L. S. , Decaria C. M. , Liebowitz M. R.
Published: December 2004

Forty‐four patients with obsessive–compulsive disorder (OCD) were entered into a double‐blind randomly assigned treatment protocol with clomipramine (CMI) or placebo. In addition, alprazolam was administered to 14 OCD patients in a separate open‐treatment study. The response rate of patients completing treatment was 50 per cent with CMI, 19 per cent with placebo, and 18 per cent with alprazolam. Self‐ratings of obsessive–compulsive symptoms in intent to treat and completer samples demonstrated a significantly greater benefit with CMI than with alprazolam. Ratings of depression and clinician ratings of obsessionality in both intent‐to‐treat and completer samples did not, however, indicate differences between the treatment groups.
Effects of mood‐stabilizing drugs on the peripheral serotonin transporter
Authors: Marazziti D. , Rotondo A. , Lenzi A. , Presta S. , Silvestri S. , Cassano G. B.
Published: December 2004

We studied the effect of lithium (L), carbamazepine (CBZ), valproic acid (VA), verapamil (VP) and nifedipine (NF) on the specific binding of 3H‐imipramine (3H‐IMI) to platelet membranes, as compared with clomipramine (CLO). The results showed that VP, NF and CLO exerted a concentration‐dependent inhibition on the IMI binding; CLO had the most potent inhibitory effect. No effect was observed with L. CBZ or VA. These results suggest that while VP and NF interact with the 5‐HT transporter complex, L, CBZ and VA do not. Therefore, their effective (or suggested) mood‐stabilizing effects are likely to be related to different mechanisms.
Stress and arousal rhythms in cigarette smokers, deprived smokers, and non‐smokers
Authors: Parrott A. C. , Joyce C.
Published: December 2004

Feelings of stress and arousal were assessed in sedative smokers (N = 26), stimulant smokers (N = 14), nicotinedeprived smokers (N = 14), and non‐smokers (N = 22). The self‐rating questionnaire was completed every 2 hours, from waking until late evening. Feelings of anxiety/stress decreased over the day in non‐smokers, and both groups of smokers, but increased in deprived smokers (group × time interactions: p < 0.001). This demonstrates the anxiogenic effects of nicotine deprivation, and confirms that one major reason for smoking is to avoid the deleterious effects of nicotine deprivation. While average daily stress levels did not differ significantly between smokers and non‐smokers, both groups of smokers started the day with higher stress than non‐smokers, but ended the day with slightly lower stress (group × time interactions: p < 0.001). Thus the gradual accumulation of nicotine does have anxiolytic effects. The arousal findings were complex, with different circadian patterns found across all four groups.
Prolactin response to zotepine in schizophrenic patients
Authors: Otani Koichi , Kondo Tsuyoshi , Ishida Masayuki , Sasa Hiroshi , Higuchi Hisashi , Kaneko Sunao , Fukushima Yutaka
Published: December 2004

The prolactin response to an antipsychotic drug zotepine, which has both antidopaminergic and antiserotonergic effects, was studied in 24 inpatients suffering from schizophrenia. The daily dose was 100 mg in the first week, and 200 mg for the next three weeks. The mean serum concentrations of prolactin at the daily dose of 200 mg, but not 100 mg, were significantly higher than that before treatment. The δ prolactin (the change from the pretreatment concentration) was significantly correlated with zotepine concentrations at each week. At low zotepine concentrations, patients with high pre‐treatment prolactin concentrations showed negative δ prolactin. The present study thus suggests that at high concentrations zotepine shows predominantly antidopaminergic effects, while at low concentrations its antiserotonergic effects are predominant and/or it acts as a dopamine agonist.
A double blind comparison of the effects of fluoxetine and amitriptyline on cognitive function in elderly depressed patients
Authors: Fairweather D. B. , Kerr J. S. , Harrison D. A. , Moon C. A. , Hindmarch I.
Published: December 2004

Sixty‐six elderly depressed patients received fluoxetine 20 mg (FLU) or amitriptyline 75 mg (AMI) for 42 days in a double blind parallel group study. Each week, subjects completed a test battery which is sensitive to the residual effects of psychoactive drugs. The results show that FLU and AMI were equally effective in relieving depression. However, the psychometric test battery showed that, compared to FLU, AMI, as expected, produced impairments in cognitive function and psychomotor performance. The relative impairment of cognitive and psychomotor skills following the tricyclic AMI and the lack of such activity after administration of the selective serotonin reuptake inhibition, FLU are important considerations when prescribing antidepressants, especially when the safety and well being of ambulant patients is essential.
Inositol 6 g daily may be effective in depression but not in schizophrenia
Authors: Levine Joseph , Gonsalves Mirtha , Babur Izak , Stier Shaul , Elizur Avner , Kofman Ora , Belmaker R. H.
Published: December 2004

Inositol is an important precursor for second messenger synthesis and has been reported to be reduced by lithium treatment in rat brain and in human CSF in depression. An open trial of 6 g/day in 11 depressed patients resistant to previous treatment led to major improvement in nine patients. The enzyme synthesizing inositol has been reported to be elevated in schizophrenia, suggesting an attempted compensation for possible inositol deficiency. A controlled double‐blind crossover trial in 10 chronic schizophrenic patients of 6 g/day of inositol for 30 days did not reveal any benefit.
Iodine‐induced delirium
Authors: Hara T. , Sato T. , Takeichi M.
Published: December 2004

A case of delirium that was believed to have been caused by disinfectant iodoform is reported. The delirium began on the seventh day following filling with iodoform gauze, and approximately one month later, the patient entered a semi‐comatose state. The patient began to recover roughly seven days after filling was discontinued. At that time, there were indications that the serum‐iodine levels was five times higher than normal. From the above, it is believed that the case of the delirium was the iodine absorbed from the filling gauze.
Caffeine and automaticity in encoding prelexical tasks: Theory and some data
Authors: Loke Wing Hong
Published: December 2004

The present study examined the integration of the automaticity theory and Yerkes‐Dodson law using a three‐factor design‐Automaticity (automatic and nonautomatic behaviors), Drug (caffeine‐high arousal and placebo‐low arousal), and Task Difficulty (low and high levels of difficulty). A specific significant three‐way interaction was predicted; that is, caffeine facilitates low difficity nonautomatic performance relative to placebo but decreases high difficulty nonautomatic performance relative to placebo, and caffeine does not affect automatic performance across levels of task difficulty relative to placebo. Three variations of the automatic/nonautomatic distinctions were used to examine its effects on the encoding and prelexical paradigm of information processing, thereby permitting a comparison of the predicted three‐way interaction. The tasks were frequency monitoring (automatic)/free recall (nonautomatic) task in Experiment 1, and a variant (of task in Exp. 1) in Experiment 2 and an alternate task (vs tasks in Exps. 1 and 2) in Experiment 3. The results of Exp. 1 showed instances of the three‐way interaction and thus, provides support for the proposed integration of the theory of automaticity and Yerkes‐Dodson law. Overall, the results of the three experiments agreed with past findings. That, automatic performance is unaffected by empirical manipulation such as drugs and nonautomatic performance is affected by the manipulation of arousal (caffeine) in Exps. 1 and 2 and task demands (difficulty) in Exps. 2 and 3. Automatic performance, however, is not insensitive to all manipulations; Exps. 1 and 3 showed that task demands (difficulty) significantly affected it. So, there is more than one form of automaticity. In sum, the present study showed a method of comparing various forms of automaticity within a single experiment and using a pharmacological agent (drug) to test concepts of automaticity and other mechanisms of information processing.
Subjective and psychomotor effects of bolus doses of nitrous oxide in humans
Authors: Dohrn Cathleen S. , Lichtor J. Lance , Coalson Dennis W. , Flemming David , Zacny James P.
Published: December 2004

Nitrous oxide, commonly used in medical settings for its anxiolytic, analgesic, and anesthetic effects, is also used recreationally. One method of using this agent recreationally is to inhale a pure bolus of nitrous oxide (N2 O) one or more times in succession. The effects of such an inhalation mode (i.e. brief inhalation of higher concentrations of N2 O) have not been adequately characterized. The present experiment examined the subjective and psychomotor effects of short duration (or bolus) administrations of a range of concentrations of N2O in healthy volunteers. We used a prospective, placebo‐controlled, double‐blind, crossover design in which N2O was administered to subjects for 45 s in concentrations of O (oxygen‐placebo), 20, 40, and 80 per cent. A number2 of subjective effects, including increased VAS ratings of ‘high,’ ‘tingling,’ ‘stimulated,’ and ‘confused’ and increased ‘euphoria’ and ‘psychedelic effects’ scores on an Inhalant Drug Effects post‐session questionnaire were found with higher concentrations of N2O (i.e. 40 per cent and 80 per cent). Subjective effects were short‐lived and had usually dissipated within several minutes of inhalation. Psychomotor performance did not differ between the first time that we measured it postinhalation (2.5 min) and pre‐inhalation (baseline), but the self‐reported time course of effects of N2O suggested that we tested post‐inhalation psychomotor performance when effects were subsiding (i.e. not when they were at their peak). We conclude that bolus concentrations of N2O produce a range of subjective effects which is consistent with its recreational use (abuse).
Repeated administration of buspirone: Absence of pharmacodynamic or pharmacokinetic interaction with triazolam
Authors: Boulenger Jean‐Philippe , Gram Lars F. , Jolicoeur Françlois B. , Zarifian Edouard
Published: December 2004

The present study was designed to evaluate possible pharmacokinetic and pharmacodynamic interactions between buspirone administered repeatedly and triazolam given acutely. Ten healthy male volunteers participated in the study and received 0.25 mg of triazolam orally after a one‐week pretreatment with either placebo or buspirone 5 mg t.i.d. The study design was double‐blind and crossover, the subjects receiving two times triazolam after the random administration of buspirone or placebo, each treatment period being separated by a washout period of 1 week. Plasma triazolam concentrations were measured by a radio‐receptor assay using 3H‐flunitrazepam as radioligand. Psychomotor effects of triazolam were measured through subjective self rating scales and various cognitive tests exploring concentration, memory and psychomotor skills.

Overall, the results of the study failed to demonstrate any significant difference in triazolam subjective or objective effects as well as in triazolam plasma concentrations after a one‐week pretreatment with either placebo or buspirone 15 mg daily. They do suggest that clinically relevant interactions are unlikely to appear when buspirone at moderate dosage is co‐prescribed with acute doses of triazolam, though these data do not exclude the possibility of pharmacokinetic interactions between the two drugs. Finally our data also suggest the need for more specific studies in order to demonstrate a possible improvement of psychomotor functions after buspirone administration.
A study of the therapeutic spectrum of a fixed‐dose of zotepine and its relationship with serum concentrations of the drug
Authors: Kondo Tsuyoshi , Otani Koichi , Ishida Masayuki , Mihara Kazuo , Tanaka Osamu , Kaneko Sunao , Fukushima Yutaka
Published: December 2004

The therapeutic spectrum of zotepine, an antipsychotic drug, and its relationship with serum concentrations of the drug were investigated by a fixed‐dose study (100 mg/day in the first week, and 200 mg/day for the next 3 weeks) in 20 schizophrenic in‐patients. The mean percentages of symptom reduction in total Brief Psychiatric Rating Scale (BPRS) and three subgroups were 63.4 per cent for total, 64.4 per cent for positive symptoms, 41.8 per cent for negative symptoms and 74.2 per cent for anxiety‐depression respectively. Total, positive and negative symptoms were significantly reduced after 2 weeks (p < 0.01), while a significant reduction in anxiety‐depression symptoms was already found after 1 week (p < 0.01). There were significant differences in the values of percentage improvement in total and positive symptoms after 2 weeks (p < 0.05) and negative symptoms after 1 week (p < 0.05) between responders (more than 50 per cent reduction in total BPRS scores at the end of the study) and nonresponders. In 18 patients (90 per cent), the clinical response at 2 weeks corresponded well to the final outcome. No definite relationship was found between serum zotepine concentrations and the clinical efficacy.
Psychomotor performance of patients on maintenance lithium therapy
Authors: Jauhar P. , McClure I. , Hillary C. , Watson A.
Published: December 2004

Lithium has changed the natural history of affective disorder, resulting in the majority of patients functioning in the community with no overt impairment in their emotional or social functioning. This study evaluated the psychomotor performance of a sample of patients stabilised on lithium, using a battery of computerised psychomotor tests. These tests reinforced previous concern regarding impairment of psychomotor functioning, parimarily reaction times, in patients on long term lithium.
Placebo‐Controlled trial of paroxetine in depressive illness
Authors: Edwards J. Guy , Goldie Ann
Published: December 2004

A randomized double‐blind placebo‐controlled trial was carried out to assess the effectiveness, tolerance and unwanted effects of paroxetine in the treatment of depressive illness. Forty‐one patients referred to a psychiatric unit in a general hospital were included in the study. Treatment lasted for six weeks. The main outcome measures were changes in scores on the Hamilton rating scale for depression and Leeds self‐assessment of ‘Depression Specific’ scale. Statistically significant improvements occurred in both treatment groups, while the end‐point differences in scores show significant advantages of paroxetine over placebo.
Modelling drug actions on electrophysiologic effects produced by EEG modulated potentials
Authors: Pagel J. F.
Published: December 2004

Drugs producing CNS behavioural effects induce consistent changes in EEG frequency modulated electrical fields. Current models which use spike potential theories of neural conduction to explain EEG frequency changes and effects have limitations and are not consistent with some experimental data. An electrophysiologic framework exists at the neuronal membrane capable of responding to extracellular electrical fields to produce changes in cellular ion concentrations and result in ATP production. Models based on active EEG effects can be utilized to explain correlations between drug behavioural effects and spatial and frequency characteristics of the EEG. Such modelling is consistent with data derived from PET scanning of the CNS, and suggests that topographic mapping of physiologic variations in EEG frequencies may be increasingly useful in the evaluation of CNS pathology.
Influence of lornoxicam a new non‐steroidal antiinflammatory drug on lithium pharmacokinetics
Authors: Ravic M. , Salas‐Herrera I. , Johnston A. , Turner P. , Foley K. , Rosenow D.
Published: December 2004

The pharmacokinetics of lithium carbonate have been studied in 12 normal young volunteers when given alone and in combination with lornoxicam, a novel non‐steroidal anti‐inflammatory drug. Peak and 12‐h lithium concentrations were significantly higher when both drugs were given together than when lithium was given alone. Caution should be exercised if and when the drugs are co‐prescribed.
5HT‐3 receptor blockade in nicotine withdrawal: Study with BRL 46470A
Authors: Park S. B. G. , Smith A. P. , Cowen P. J.
Published: December 2004

Sixteen healthy male volunteers who smoked at least 20 cigarettes a day and satisfied DSM‐IIIR criteria for nicotine dependence were recruited to investigate the possible effects of a selective 5HT‐3 receptor antagonist (BRL 46470A) on acute nicotine withdrawal. The study was of a double‐blind, placebo‐controlled, four‐way crossover design using two doses of BRL 46470A (0.1 and 10 μg) and one dose of lorazepam (1 mg). Outcome measures included visual analogue ratings for nicotine withdrawal and a battery of psychological performance tests. Except for an effect of BRL 46470A (0.1 μg) to decrease subjective rating of confusion, none of the drug treatments attenuated subjective measures of nicotine withdrawal. Lorazepam significantly impaired performance on all three tests of neuropsychological function, but BRL 46470A was without effect on these measures.
Antidepressants and mania: To stop or not to stop?
Authors: Allen Danny , Horvath Rob , Nutt David
Published: December 2004

The clinical problem of whether to stop antidepressants when patients develop mania is looked at in the light of existing practice and advice both in the UK and in the USA. It is concluded that practice is based more on an empirical than a scientific basis. The literature on the subject is reviewed with especial reference to the questions of whether antidepressants actually cause mania, whether they interfere with the treatment of mania, whether discontinuing them stops mania and whether withdrawal of antidepressants causes mania. Finally a case notes study conducted by one of the authors is summarized and recommendations for further research are made.
Application of transcranial magnetic stimulation in treatment of drug‐resistant major depression—a report of two cases
Authors: Höflich G. , Kasper S. , Hufnagel A. , Ruhrmann S. , Möller H.‐J.
Published: December 2004

We report the cases of two drug‐resistant major depressed psychotic patients, who were treated with 10 sessions of transcranial magnetic stimulations (TMS) and afterwards with 10 sessions of electroconvulsive therapy (ECT) without changing the concomitant neuroleptic and antidepressive medication. TMS did not exert a therapeutic effect in one patient and only a slight one in the other. However, there was a clear beneficial effect for ECT in the patient not responding to TMS and a slight therapeutic effect in the other. In summary, there was no clear‐cut evidence for effectiveness of TMS as a treatment for patients with psychotic, therapy resistant depression. However, since there was a slight therapeutic effect of TMS in one patient it seems worthwhile to explore its therapeutic efficacy in a larger group of depressed patients.
Cognitive and motor function impairments during continuous opioid analgesic infusions
Authors: Coda Barbara A. , Hill Harlan F. , Hunt Earl B. , Kerr E. Beth , Jacobson Robert C. , Chapman C. Richard
Published: December 2004

This research was supported in part by grants from National Cancer Institute (CA 38552) and assistance from Janssen Research Foundation.

Morphine and other opioid analgesics may interfere with normal cognition and motor function during long‐term treatment of cancer‐related pain. In this study, we used individually tailored steady‐state drug infusions to control plasma concentrations of morphine and alfentanil and measured the extent of cognitive and motor impairments produced by each drug in healthy volunteers. The tailored infusions allowed evaluation of cognitive and motor effects at three sequential, steady plasma concentrations of each opioid. During continuous infusion, both drugs caused significant, plasma concentration‐related impairments of ability to process serially‐presented information and of fine motor control at plasma drug concentrations within the usual therapeutic range. We found significant relationships between cognitive and motor function decrements and plasma opioid concentration with both morphine and alfentanil. We conclude that magnitudes of cognitive and motor function impairments are equivalent for these two mu receptor selective agonists at equianalgesic plasma concentrations.
Alpidem: Lack of sedative effect on psychomotor performance in therapeutic doses
Authors: Rosenzweig P. , Warrington S. , Patat A. , Ascalone V. , Bergougnan L. , Morselli P. L.
Published: December 2004

This is a randomised, double blind, cross‐over, placebo‐controlled study carried out in 12 healthy young male volunteers. It consisted of six test days separated by two week wash‐out periods. The objective was to compare the potential sedative effects of 3 single oral doses of alpidem (50 mg, 100 mg and 200 mg) versus diazepam (10 mg and 15 mg). Pharmacodynamics were assessed by objective psychometric tests (critical flicker fusion, choice‐reaction time, manual dexterity, digit span) and subjective evaluation (visual analogue scales) before then 2 h, 4 h, 8 h and 24 h post‐dose.

Alpidem in dosages of 50 mg and 100 mg did not impair alertness or psychomotor performance; with 200 mg, psychometric tests and visual analogue scales demonstrated sedative effects 2 h post‐dose.

In contrast, diazepam in a therapeutic dosage (10 and 15 mg) produced similar impairments of vigilance and psychomotor performance as alpidem 200 mg, indicating a lack of dissociation between anxiolytic and sedative effects.
Natural killer cell activity and serum immunoglobulins in epileptic patients
Authors: Testorell Carla , Pruneri Carlo , Ferini‐Strambi Luigi , Zamperetti Marco , Altamura Carlo A. , Smirne Salvatore , Bareggi Silvio R.
Published: December 2004

Serum immunoglobulins and the activity of natural killer (NK) cells of 50 epileptic patients (eight with idiopathic generalized epilepsy and 42 with cryptogenic partial epilepsy) and 28 controls have been studied. The values of IgA, IgG and IgM were the same‐in patients and controls. The NK activity in controls was linearly related to the effector‐to‐target ratio, but this linear relationship was not observed in epileptic patients. The cytotoxic activity of NK cells at the lowest effector‐to‐target ratio was significantly greater in patients than in controls. This increase was observed in each therapy group. Our results seem to confirm a disturbance of the immune system in epileptic patients and suggest that this modification of cellular immunity is not a drug effect but is related to the illness itself.
Safety and antidepressant efficacy of selective serotonin re‐uptake inhibitors
Authors: Kasper S. , Höflich G. , Scholl H.‐P. , Möller H.‐J.
Published: December 2004

This review deals with the safety and antidepressant efficacy of selective serotonin re‐uptake inhibitors (SSRIs). At present, five SSRIs are used therapeutically in European countries (fluvoxamine, fluoxetine, paroxetine, sertraline and citalopram). The antidepressant efficacy of these drugs has been tested both versus placebo and versus reference antidepressants (amitriptyline, imipramine) revealing comparable antidepressant efficacy to the active compounds and a significant superiority compared with placebo. Furthermore, the available studies provide initial evidence that SSRIs have good antidepressant efficacy in severe depression and suggest that they might lead to a faster decline of suicidal tendencies within major depression. Since they have a favourable side‐effects profile in sum, compared with tri‐ and tetracyclic antidepressants, they can be recommended from the aspect of a ‘side‐effects‐derived indication’.
Lithium and anticholinergic combination to maintain a stable lithium plasma level
Authors: Bellibas S. Eralp , Ülker Sibel , Akfert Kazim , Tuglular Isik , Vahip Simavi
Published: December 2004

The effect of lithium and propantheline, an anticholinergic agent, combination on plasma and red blood cell (RBC) lithium levels was studied to test if this combination could maintain a stable plasma lithium level for a long‐lasting period by delaying gastric emptying, in rabbits. There was a significant difference in plasma lithium levels between control and propantheline‐administered groups (p < 0·01). The peak level seen in the second hour of lithium administration in the control group was not observed in the propantheline‐administered group and a stable lithium level was maintained. It was suggested that a lithium and anticholinergic drug combination can be an alternative in eliminating the peak plasma levels of lithium and preventing the side‐effects thought to be related to this factor.
A comparison of the psychometric effects of remoxipride with those of haloperidol, thioridazine, and lorazepam in healthy volunteers
Authors: Hindmarch I. , Tiplady B.
Published: December 2004

In this placebo and verum (lorazepam 2 mg) controlled double‐blind crossover study the acute effects of Remoxipride 50 mg and 100 mg; Haloperidol 2·5 mg; and Thioridazine 50 mg were examined in 18 healthy volunteers. CNS function was assessed using a battery of psychometric measures, viz: Critical Flicker Fusion Threshold (CFFT); Choice Reaction Time (CRT); Tracking Accuracy (RMS) and Peripheral Reaction Time (PRT); Sternberg Memory Scanning (SMS); Word Memory (WM) as well as Line Analogue Ratings of subjective sedation (LARS) and the Leeds Sleep Evaluation Questionnaire (LSEQ). Both doses of remoxipride were associated with a reduction of CFFT: 0·9 Hz for 50 mg and 1·3 Hz for 100 mg. The 100 mg dose caused an increase (impairment) in CRT total time of 38 msec. Haloperidol reduced CFFT, while thioridazine and lorazepam impaired performance on the majority of objective measures, as expected for known sedative drugs. Thioridazine led to hypotension in three subjects, and to subjective sedation (LARS), but no treatment affected responses on the LSEQ administered the morning of the day following treatment. These results show that remoxipride has some depressant effects on CNS function, but that these are less prominent than those of sedative neuroleptics such as thioridazine.
Nine parallel versions of four memory tests: An assessment of form equivalence and the effects of practice on performance
Authors: Watson Frances L. , Pasteur Mary‐Anne L. , Healy David T. , Hughes Elizabeth A.
Published: December 2004

Four memory tests, each containing nine parallel forms, were developed and assessed for their suitability for use in psychopharmacological research. The tests measured verbal memory, face‐name‐occupation associate learning, spatial location memory and memory for visual designs. Twenty‐seven healthy subjects completed a different form of each test on each of nine testing occasions. Test form administration order was rotated across subjects to permit the independent assessment of practice effects and test form equivalence. Performance on four of the test forms differed significantly from performance on other forms of the same test. Data from the remaining forms contained no significant test form differences and these were assumed to be equivalent. ANOVA indicated practicerelated changes in six of the seven measures examined. Four or five successive test sessions were required before performance stabilized. Initial ‘dips’ in performance observed in the verbal memory tests were attributed to proactive interference, whilst further performance improvements in spatial location performance that occurred in the last three days of the study may have been caused by the development of mnemonic strategies. Thus, patterns of change with practice varied across the four tests. The results underline the importance of documenting practice effects in relation to repeated memory assessment.
Predictors of dental anxiety and effects of treatment with nitrous oxide and midazolam in dentally phobic patients
Authors: Goodall Elizabeth M. , Skelly Ann M. , File Sandra E.
Published: December 2004

The role of general anxiety measured by the Hospital Anxiety and Depression Scale (HADS), or the Spielberger Trait Anxiety scale, (STAI‐T) on dental anxiety (measured by the Corah Dental Anxiety Scale, the Kent Phobia Scale and by analogue ratings concerning specific procedures) of dentally phobic patients was examined using multiple regression analysis. HADS anxiety and STAI‐T scores were both significant predictors of Corah scores; whereas HADS depression and STAI‐T predicted Kent scores, which measure how concerns about dentistry affect emotional and social well‐being. Fear of coming for an appointment significantly contributed to both scores and was itself predicted by anxiety about having an instrument in the mouth. The effects of sedation with nitrous oxide or midazolam on the change in dental anxiety after two treatment sessions in patients with high or low HADS anxiety were compared. Both drugs resulted in significant and equal reductions in scores on the Corah scale and anxieties about an instrument in the mouth, drilling and filling, in both high and low anxiety groups. None of the groups showed a significant reduction in scores on the Kent scale or in fear of coming for an appointment.
Zopiclone, sleep and health‐related quality of life
Authors: Goldenberg F. , Hindmarch I. , Joyce C. R. B. , Le Gal M. , Partinen M. , Pilate C.
Published: December 2004

458 insomniac patients participated in a multinational, randomised, double blind, parallel groups study of zopiclone 7.5 mg versus placebo. Patients received the drug or placebo nightly for 14 days and for a further six weeks on demand. Sleep characteristics and Quality of Life measures were assessed at 14, 28 and 56 days after admission. Both groups of patients improved on these measures, but the active treatment showed significantly greater improvement compared to placebo, both after 14 days and at the end of the trial.
Thrombocytopenia associated with levomepromazine: A case report
Authors: Sato T. , Takeichi M. , Takami T.
Published: December 2004

Cases of blood dyscrasia related to neuroleptic therapy have been reported. However thrombocytopenia associated with levomepromazine (LPZ) has never been reported, to the best of our knowledge. We describe here a patient treated with LPZ who has developed haemorrhagic vesicles and severe thrombocytopenia. Appropriate management and prompt substitution of LPZ by sulpride led to a full clinical recovery.
LSD: A missed opportunity?
Authors: Claridge Gordon
Published: December 2004

Despite its early promise as ‘the chemical key to schizophrenia’, and its manifest properties as a psychotomimetic, LSD failed to catch on as a drug model for human psychosis. The reasons for this and the longstanding preference, instead, for the amphetamine model are examined. It is argued that the rejection of LSD was not just a scientific decision, but was influenced by increasing disaffection in psychiatry and society at large with psychological (existentialist) interpretations of schizophrenia with which LSD, as a recreational drug, was associated. The proscription of LSD and the shift towards a strongly organic view of schizophrenia created a climate where it was easier to accept the simpler amphetamine (dopamine) model. Flaws in the latter, its further recent undermining as an exclusive theory, and challenges to an overly organic psychiatry by a more psychobiological approach, are all discussed in the light of the perceived need for a more elaborated neurochemical account of schizophrenia; this includes a rǒle for central serotonergic influences in the disorder, removing much of the previous objection to LSD as a drug model. Several ways are suggested in which data about LSD could still usefully be drawn upon in schizophrenia research; including, in animal experimentation, its direct use to test the viability of the various biological models of schizophrenia on offer. Some examples of the latter are given, including a study of LSD from the author's own past work.
The role of growth factors and neuropeptides in alzheimer's disease
Authors: Wilcock G. K.
Published: December 2004

A number of important neurotransmitter deficiencies have been described in Alzheimer's disease, the commonest cause of dementia in people at all ages. Particularly marked is the depletion of acetylcholine, and a number of treatments have been developed which are aimed at correcting this biochemical deficiency, so far with varying success. An alternative strategy involves the use of neurotrophic compounds to try and prevent or retard the loss of cholinergic cells, reducing the magnitude of acetylcholine depletion. A number of different neurotrophic compounds are exciting interest in this context, especially Nerve Growth Factor (NGF). Animal and tissue culture studies support a neuroprotective role for NGF in relation to cholinergic neurons and human recombinant NGF is being produced with a view to small scale clinical trials in the not too distant future. The ‘active’ parts of the NGF molecule are being identified to enable the development of simpler molecules with biological activity that may more easily penetrate the blood‐brain barrier. Other members of the neurotrophin family are also under investigation as potential treatments for a range of neurodegenerative disorders, including Alzheimer's disease.
Tissue adhesives and hemostasis‐inducing compounds: The alkyl cyanoacrylates
Authors: Leonard F. , Kulkarni R. K. , Nelson J. , Brandes G.
Published: December 2004

In an effort to obtain tissue adhesive monomers which would wet and spread on tissue substrates and be rapidly biodegradable, the branched esters of alkyl α‐cyanoacrylates, as well as a 95‐5 wt.‐% mixture of n‐heptyl and methyl α‐cyanoacrylate, were studied. The data indicate that alkyl α‐cyanoacrylates having branched alkoxy groups appear to be promising in this regard.
The in vivo metabolic degradation of poly (methyl cyanoacrylate) via thiocyanate
Authors: Kulkarni R. K. , Hanks G. A. , Pani K. C. , Leonard F.
Published: December 2004

Methyl α‐cyanoacrylate, when implanted subcutaneously in rats and dogs, has been shown to lead to an increase in thiocyanate output in the urine, presumably through the formation of cyanide anions which are subsequently converted to thiocyanate. It is postulated that this reaction may be one of the reactions contributing to tissue necrosis when methyl α‐cyanoacrylate is used as a tissue adhesive.
Problems of materials in mechanical heart systems
Authors: Akutsu Tetsuzo , Kantrowitz Adrian
Published: December 2004

Currently available materials for mechanical heart systems are surveyed, particularly with respect to long‐term implantation, from the viewpoints of availability and workability, mechanical and biological durability, and compatibility with blood and tissue. Some materials have one or more desirable physical properties, but none offers perfect blood and tissue compatibility. Medical grade Silastic, considered best for blood handling parts, has produced promising results in auxiliary ventricle patency experiments. The insufficient tensile strength of Silastic should be increased, and it may be possible to accomplish this while maintaining the present resilience, elongation, and inertness. No long‐term data on thrombus formation are available, but clot‐retarding quality is essential and may perhaps be obtained by incorporating heparin. Developments in polymer chemistry may also lead to other surfaces with the requisite mechanical properties with blood.
Improved hemodialysis membranes for the artificial kidney
Authors: Luttinger M. , Cooper C. W.
Published: December 2004

A major part of current effort in improving artificial hemodialysis techniques concerns the development of improved membrane structures. Although blood compatibility of membranes is a part of the Battelle program, this discussion is confined to membrane composition, structure, and transport. On the basis of a need for improved hemodialysis techniques, membranes for use in the artificial kidney were prepared and evaluated for urea, creatinine, and uric acid permeability. Water‐soluble polymers were crosslinked to form insoluble, but swellable, membranes. Faster metabolic waste transfer than with the conventional cellulosic membranes was obtained with diisocyanate‐crosslinked poly (vinyl pyrrolidone) and poly (vinyl pyrrolidone)–dextran membranes and with membranes obtained by crosslinking poly (vinyl alcohol) with polyfunctional aldehydes. Membranes prepared from emulsions of vinyl pyrrolidone–ethyl acrylate and vinyl pyrrolidone–styrene copolymers had exceptionally high urea and creatinine dialysis rates, but were deficient in uric acid transfer. This shortcoming was corrected by incorporating solutes such as sucrose into the membranes followed by leaching. Another important approach concerned the development of a relatively high‐strength membrane based on an impermeable nylon resin. Permeability of these membranes which have dialysis characteristics superior to those currently used was obtained through the addition of DMSO and one of several other additives to the coating solution.
Preliminary considerations for flexural endurance testing of semicrystalline polymers for biomedical materials standards
Authors: Lontz John F.
Published: December 2004

Semicrystalline polymers used as restorative prostheses in the cardiovascular system require more detailed consideration of flexural fatiguing with simple physical characterization and mechanical measurements as one basic means for developing test standards and specification levels for biomedical research materials. Such initial means are considered with polytetrafluoroethylene as a reference polymer nominally inert chemically used to illustrate one approach to assessing morphological and structural changes with a flex tester. Density measurements and void content have been carried out to provide one means of assessment whereby the corresponding crystallinity and permeation can be considered for more detailed correlation to cytological interactions as the polymers are used as replacement components in the cardiovascular system. Progressive flexural cycling up to 106 cycles at a 3 cps rate indicate significant decreases in crystallinity simultaneously with increasing void content. As an accelerated test, the implications for extrapolation to 25‐year fatiguing in normal physiological cycling rate are conjectured to provide a starting point for more realistic, cyclic ex vivo screening of biomaterials.
Velour fabrics applied to medicine
Authors: Hall C. William , Liotta Domingo , Ghidoni John J. , De Bakey Michael E. , Dressler Donald P.
Published: December 2004

Warp‐knitted velour fabrics of Dacron, nylon, polypropylene, and Rayon have been backed with Silastic to form a laminate. Prior to heat curing, the composite can be molded into many shapes and has been successfully used to line the luminal side of blood pumps and vascular grafts. Prosthetic heart valves are being covered with velour in an attempt to promote a more compatible surface. Velour suture rings are being evaluated as a more efficient anchor for prosthetic heart valves. Silastic tubes with velour bonded to the outer wall have been used to inhibit infection and sinus tract formation where percutaneous lead wires and conduits are necessary. As a flat sheet, the Silastic‐velour laminate has been used experimentally as an artificial skin, but the most noteworthy experimental results have been obtained in rats using a double layer of nylon velour, separated by an impermeable layer of poly(vinyl fluoride). Future application will include attempts to anchor artificial limbs via a velour interface and made functional by tendinous attachment.
Porous plastic prostheses
Authors: Hill James T. , Eaton James C. , Mouhot Henry G. , Leonard Fred
Published: December 2004

Porous laminates prepared by incorporating a volatile solvent into an epoxy resin system used to impregnate a fabric filler satisfactorily alleviated the problems caused by perspiration in upper extremity prostheses, but did not have sufficient strength for use in artificial legs. A new technique is described which results in a 100% increase in both porosity and strength of porous epoxy laminates. The method consists of impregnation of the fabric with resin and solvent and evaporation of the solvent prior to laying up the laminate. The improvement in properties is ascribed to better control and homogeneity of impregnation.
Microstructure of initial thrombus formation on foreign materials
Authors: Dutton Robert C. , Webber A. J. , Johnson S. A. , Baier R. E.
Published: December 2004

By reflected light microscopy, the thrombi formed on a variety of foreign surfaces have been shown to be composed of isolated cellular aggregates and an interaggregate red cell fibrin mesh. The thrombi viewed by this method were seen in two dimensions as they formed at the foreign surface blood interface. Standard histological evaluation of the thrombi in the third dimension, that is in the depth dimension, revealed columnar shaped cellular aggregates extending from the foreign surface into the blood and a red cell fibrin mesh surrounding the aggregates. The thrombi formed at Epon plate‐blood interfaces were viewed with an electron microscope. Plates made of Epon embedding epoxy were used as the foreign surface exposed to blood, and the plates and fixed initial thrombi formed on them were embedded in more Epon. A layer of heavy metal staining, noncellular material was found covering the surface of the plates exposed to blood, with platelets deposited on this layer. Since platelets were not found adherent to the foreign surfaces directly, it is our postulate that the intervening film “conditions” the surface preliminary to platelet adhesion.