bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep inertia following triazolam‐induced recovery sleep
Authors: Balkin T. J. , O'donnell V. M. , Kamimori G. H. , Redmond D. P. , Belenky G.
Published: December 2004

The effect of triazolam on prior‐sleep‐mediated performance deficits (sleep inertia) was assessed. On Day 1, subjects (45 healthy males, aged 18–39, tested in groups of two to four) reported to the laboratory at 0800 h, at which time electrodes were attached for continuous ambulatory recordings of EEG, EMG, EOG, and EKG. Addition tests of 3 min duration were administered at 1400, 1405, 1410, 1415, 1420, and 1425 h. After each test a Stanford Sleepiness Scale (SSS) was given to assess self‐rated sleepiness. Subjects were then kept awake until 0800 h on Day 2, when they were administered 0·5, 0·25, 0·125 mg triazolam or placebo. Subjects attempted to sleep from 0800 to 1400, at which time they were awakened (if asleep) and again administered the addition tests and SSSs. of 45 subjects, 24 were asleep during the 5 min period prior to testing, and only these were included in the analyses. A main effect of Day indicated decrements in addition speed on Day 2, F(1,20)=10·54, p=0·004, and a Day × Test interaction indicated sleep inertia effects, F(5,100)=6·18, p=0·0001. Differential drug effects were indicated by a significant Day × Drug interaction, F(3,20)=3·19, p=0·046, and post‐hoc analyses revealed that the number of problems attempted was significantly lower on Day 2 only for the 0·5 mg triazolam group. It was concluded that sleep inertia is exacerbated by 0·5 mg triazolam.
Metabolism of the benzodiazepine antagonist 11C‐Ro 15‐1788 after intravenous administration in man
Authors: Swahn Carl‐Gunnar , Persson Anders , Pauli Stefan
Published: December 2004

The metabolic fate of the benzodiazepine antagonist RO 15‐1788 labelled with 11C was studied in plasma from human subjects after intravenous administration in connection with positron emission tomography. Ro 15–1788 and its metabolites were separated by thin‐layer chromatography and the radioactivity in the different compounds was determined. 11C‐Ro 15–1788 was extensively and rapidly metabolised to the corresponding free acid. At 36 minutes after administration only 50% of the radioactivity in plasma represented unchanged compound.
A case of Parkinson's disease exacerbated by fluoxetine
Authors: Chouinard Guy , Sultan Sarah
Published: December 2004

Fluoxetine (Prozac®) is a potent serotonin (5‐HT) reuptake inhibitor which has rapidly gained popularity as a first‐line antidepressant due to its favourable side‐effect profile. However, it has recently been reported to worsen drug‐induced parkinsonism when used in conjunction with neuroleptics (Bouchard et al., 1989; Tate, 1989; Brod, 1989). Since fluoxetine inhibits hepatic microsomal enzymes, a pharmacokinetic interaction cannot be ruled out in such cases — the drug is known to interact with other psychotropic drugs such as MAO inhibitors (Sternbach, 1988; Feighner et al., 1990) and tricyclic antidepressants (Bell and Cole, 1988; Vaughan, 1988; Goodnick, 1989; Schraml et al., 1989; Kahn, 1990) via this mechanism among others. So far, fluoxetine has not been reported to worsen symptoms in patients with Parkinson's disease (PD) who have never received neuroleptics. Bouchard et al. (1989) observed that other selective 5‐HT reuptake inhibitors might exacerbate PD, and Meltzer et al. (1979) described a bipolar patient who developed an acute dystonic reaction, with parkinsonian rigidity and increased serum prolactin when treated with fluoxetine for psychotic depression. Fluoxetine has been implicated in the development of neuroleptic malignant syndrome (Halman and Goldbloom, 1990) and akathisia (Lipinski et al., 1989; Baldwin et al., 1991), which may also be linked to central dopaminergic blockade. A recent review of extrapyramidal tract disorders in association with fluoxetine and fluvoxamine, another selective 5‐HT uptake blocker, noted the absence of unambiguous cases and the lack of objective documentation of psychopathological and neurological changes, even though evidence for a causal relationship was compelling (Baldwin et al., 1991).
Benzodiazepines, amnesia and sedation: Theoretical and clinical issues and controversies
Authors: King D. J.
Published: December 2004

The amnestic effect of benzodiazepines, first described in 1965, and the subsequent attempts to identify the precise nature of this effect, are reviewed. The difficulty in deciding to what extent this effect is secondary to the sedative action of these drugs is shown by the lack of agreement between studies. Nevertheless, it is concluded that, given the right experimental design, all benzodiazepines can be shown to cause an anterograde amnesia which is probably primarily a result of reduced attention or rehearsal and secondary to sedation. Its onset, degree and duration are influenced by dose, rate of absorption, route of administration, potency and the receptor occupancy rate of the particular benzodiazepine involved, but plasma elimination t½ appears to be relatively unimportant. The clinical relevance of this for the long‐term use of hypnotics and anxiolytics is not clear. Tolerance appears to be greater than for the anxiolytic but less than the sedative or anticonvulsant effect of benzodiazepines. It seems that transient amnestic effects could occur in chronic users related to post‐dose, peak benzodiazepine levels. The great variability in individual response means that transient amnesia is a potential adverse drug reaction in certain individuals taking benzodiazepines.
The plasma haloperidol and reduced haloperidol concentrations in chinese schizophrenic patients: Relationship between reduced haloperidol/haloperidol ratio and red blood cell haloperidol reductase activity
Authors: Wong B. Y. M. , Chan Mo‐Yin , Wong M. T. H. , Lieh‐Mak F.
Published: December 2004

Fifteen chinese schizophrenic patients were given titrated doses of haloperidol (0.05‐0.42 mg/kg) for two weeks. All these 15 patients were in clinical remission on maintenance dose of haloperidol. The mean plasma haloperidol and reduced haloperidol concentrations were 16.8 ± 4.8 ng/ml and 13.6‐ 5.7 ng/ml respectively. The plasma RHAL/HAL ratio was in the range of 0.13±1.94. These values were similar to that reported for the Japanese population. The frequency distribution appeared to be bimodal. RBC reductase activity were found to be distributed normally and no correlation was found between plasma RHAL/HAL ratio and RBC reductase activity.
Possible relationships between carbamazepine metabolites levels and prophylactic efficacy
Authors: Kudriakova Tatyana B. , Sirota Lev A. , Kostyukova Elen G. , Gorkov Vladimir A.
Published: December 2004

Levels of carbamazepine, carbamazepine‐10,11‐epoxide and −10,11‐diol were measured in the plasma of 40 patients with affective disorders chronically treated with carbamazepine. Steady‐state plasma levels of carbamazepine were not related to the degree of prophylactic response. In contrast, the mean plasma concentrations of the −10,11‐epoxide metabolite of carbamazepine were significantly lower in patients with complete response than in patients with partial response or in nonresponders. The ratios of carbamazepine‐10,11‐diol concentrations to the parent drug dose were found to be significantly different in the three response groups. These results suggest that the pharmacokinetic parameters of the metabolites might be used for the prediction of individual prophylactic efficacy at the initial stage of carbamazepine therapy.
Physical dependence following zopiclone usage: A case report
Authors: Thakore J. , Dinan T. G.
Published: December 2004

A single case report is presented in which zopiclone was used in a patient as a hypnotic. The patient developed physical dependence. It is suggested that the adverse effects of zopiclone relate to its mechanism of action. Like other hypnotics it binds to the gamma‐aminobutyric acid (GABA)‐benzodiazepine‐chloride ionophore receptor complex. This may explain the means by which zopiclone can cause dependence.
A comparison of the effect of lofepramine, maprotiline and placebo on information processing in healthy volunteers
Authors: Hopes H. , Wandmacher J.
Published: December 2004

Single oral doses of lofepramine (140 mg), maprotiline (100 mg), and placebo were administered in a randomized three‐way crossover design with 1 week wash‐out between administrations to 12 healthy male volunteers. Before, and 1, and 3 h post‐administration a battery of performance tests was administered which included a digit‐matching paradigm and a reaction test separating recognition and motor time. In contrast to maprotiline, lofepramine did not impair speed and accuracy of cognitive performance.
The life expectancy of schizophrenic patients with tardive dyskinesia
Authors: Inada Toshiya , Koshiishi Mika , Ohnishi Kimio , Yagi Gohei
Published: December 2004

Relationships between tardive dyskinesia (TD) and the life expectancy of schizophrenic patients who suffer it were examined in two studies over a 50‐month period. In a prospective study, the mortality rate was found to be higher in patients with TD than in those without. This suggests either that TD is a factor tending to precipitate death, or else that it is an indication that the final period of life has been reached. The failure in the prospective study to detect medical factors which would discriminate between those TD patients who died and those who remained alive, as well as the finding of a significantly older age at death of patients with TD in the retrospective study may both support this idea. No significant differences were observed in the retrospective study in the prevalence of TD between 35 pairs of age‐matched deceased and living patients. The effects of TD on life expectancy are subtle; the present results are consistent with the possibilities both that TD reduces life expectancy and that it appears at the end‐stage of life.
The effects of acute and repeated doses of moclobemide on psychomotor performance and cognitive function in healthy elderly volunteers
Authors: Kerr J. S. , Fairweather D. B. , Hindmarch I.
Published: December 2004

The effects of moclobemide, a new selective and reversible MAO‐A inhibitor, on cognitive function and psychomotor performance were measured in 12 healthy elderly male volunteers (with a mean age of 72.5 years). Subjects received moclobemide 200 mg, amitriptyline (positive internal control) 25 mg or placebo twice daily and were assessed on a battery of psychometric tests on the mornings following the first (acute) day and seventh (sub‐chronic) day. The tests were: Choice Reaction Time; Tracking; Critical Flicker Fusion Threshold; Memory Scanning; Continuous Attention Task; the Leeds Sleep Evaluation Questionnaire and a Visual Line Analogue Rating Scale. The results show that amitriptyline produced impairment of cognitive and psychomotor functions. Moclobemide, however, did not disrupt sleep or cause daytime sedation, and remained neutral in the assessment of behavioural toxicity.
A comparative study of on‐the‐road and simulated driving performance after nocturnal treatment with lormetazepam 1 mg and oxazepam 50 mg
Authors: Volkerts E. R. , van Laar M. W. , van Willigenburg A. P. P. , Plomp T. A. , Maes R. A. A.
Published: December 2004

The main purpose of this study was to compare the sensitivity of a driving simulator test model (TS2) with a standard on‐the‐road driving test, after one night treatment with lormetazepam 1 mg, oxazepam 50 mg (as a verum) and placebo. The secondary purpose was to measure the effects of the intended drugs and placebo in the same subject sample, after two treatment nights in the morning and in the afternoon, on on‐the‐road driving performance. Eighteen healthy male volunteers received the three treatments (2 consecutive nights each) according to a double‐blind, three‐way crossover design. Time of administration was set at 22.00 hours each night. An on‐the‐road driving test and a simulator driving test were conducted in the morning following the first night. After the second treatment night, on‐the‐road driving tests were performed in the morning and in the afternoon. The on‐the‐road driving test consisted of operating an instrumental automobile over a 100 km highway circuit at a constant speed (90 km/h) and constant steady lateral position between the right lane boundaries. Primary performance measure was the SD of lateral position (SDLP). The simulator test consisted of repeatedly performing ‘curve‐following’ manoeuvres, which was the main tracking control task, while simultaneously reacting to secondary visual signs. Test parameters were the number of correctly executed manoeuvres (TC) and reaction time (RT). Oxazepam 50 mg seriously impaired, and lormetazepam 1 mg slightly impaired, on‐the‐road driving performance in the morning, both after the first and second treatment night. The drugs produced no significant effects in the afternoon test following the second night. In contrast with these results, neither oxazepam 50 mg nor lormetazepam 1 mg affected simulator tracking control after one night. No deterioration was found for reaction time. Correlational and multiple regression analyses were applied to determine relationships between SDLP, TC and RT. The major conclusion of this study was that the TS2 driving simulator test does not predict residual drug effects in the on‐the‐road driving test, and seems to be a less sensitive measure of sedative drug‐induced impairment in contrast to the on‐the‐road driving test.
Studies on the binding of [3H]flumazenil and [3H]sarmazenil in post‐mortem human brain
Authors: Hall H. , Litton J.‐E. , Halldin C. , Kopp J. , Sedvall G.
Published: December 2004

Two benzodiazepine analogues, [3H]flumazenil and [3H]sarmazenil, were used to study the GABAA/benzodiazepine receptor complex in human post‐mortem brain using in vitro receptor assays on homogenates and whole hemisphere autoradiography. Both radioligands bound in a saturable manner to single binding sites in the tissue preparations from any brain region. The highest levels of binding were found in the cortical regions and in cortex cerebelli. Both [3H]flumazenil and [3H]sarmazenil were excellent radioligands for autoradiography with high binding in cerebral and cerebellar cortex with no or very low binding in areas with white matter. The addition of a high concentration of flumazenil or clonazepam did not inhibit the binding of [3H]sarmazenil to granule cells in the cerebellum while the binding of [3H]flumazenil was abolished completely in all regions. The results show that with the two different radioligands, one an antagonist and one a partial inverse agonist, the binding pattern to GABAA/benzodiazepine receptor complex is approximately similar in most brain regions. The additional binding seen in the cerebellum with [3H]sarmazenil is suggested to be due to binding to an α6‐containing complex.
Plasma and breast milk concentrations of dothiepin and northiaden in lactating women
Authors: Buist Anne , Norman Trevor R. , Dennerstein Lorraine
Published: December 2004

Plasma and breast‐milk concentrations of dothiepin and its metabolite northiaden were measured in 20 lactating women receiving the drug for post‐partum depression. Samples were collected at steady‐state and both compounds quantitated by HPLC. Doses of dothiepin varied from 75 mg/day to 225 mg/day. Accordingly a wide range of plasma and breast‐milk concentrations of dothiepin and northiaden were determined. Most determinations were made for women receiving 150 mg/day. At this dose mean (± SD) plasma concentrations of dothiepin and northiaden were 56(±27)m̈g/l and 72(±79)m̈g/l respectively while breast‐milk concentrations were 95(±71) m̈g/l and 40(±29) m̈g/l for dothiepin and northiaden respectively. The data reflect the well recognised inter‐individual variability in plasma concentrations for subjects receiving the same oral dose. Similar variability was noted in breast‐milk concentrations at all doses of dothiepin. Dothiepin passes into the breast‐milk of lactating women receiving the drug for post‐partum depression. In this respect the drug is similar to other tricyclic antidepressants. The inter‐individual variability of results recorded here suggest the need to determine drug concentrations on an individual basis before reaching a decision about breastfeeding. Perceived side effects in the infant are clear criteria for cessation of breastfeeding; high levels of drug in breastmilk where the infant is unaffected, warrant monitoring in view of our inadequate knowledge regarding long term effects of these drugs.
Fluoxetine in the treatment of amphetamine dependence
Authors: Polson R. G. , Fleming P. M. , O'shea J. K.
Published: December 2004

Evidence of increasing prevalence of amphetamine mis‐use, with a concomitant increase in intravenous administration of the drug, highlights the need for better alternatives to the current pharmacological interventions available for the treatment of amphetamine withdrawal symptoms, and prevention of relapse. A number of amphetamine analogues are neurotoxic to serotonergic neural pathways. In addition, there is evidence of reduced activity in serotonergic pathways in individuals with antisocial personality disorder and substance abuse. We report on the use of fluoxetine in eight cases of whom four achieved abstinence. Three cases reported a reduction in amphetamine use and only one reported no change in the level of use. Control studies are indicated and the use of fluoxetine in relapse prevention warrants further investigation.
A nicotine dependent and a nicotine independent component of smoking related pulse and activity variation
Authors: Jacober A. , Hasenfratz M. , Bärttig K.
Published: December 2004

In a field study, heart rate and motor activity were continuously assessed during two days in smokers, abstinent smokers and non‐smokers. Smoking abstinence reduced heart rates by about 10 bpm to the non‐smoker level without affecting motor activity. Averaging heart rate and activity using lighting of the cigarettes as the triggering event revealed the characteristic profiles described previously. Both variables increased during the last five minutes before lighting the cigarettes and decreased immediately upon lighting to near or even below the prelighting levels. This lighting response was maintained in a similar fashion when the subjects marked the time points of the desire for smoking but omitted lighting the cigarettes and it remained highly similar for the first and last five cigarettes of the day. In non‐smokers a similar pattern was also obtained using the first sip of coffee as triggering event. In smoking smokers, this lighting response was followed by an increase of heart rate without changes in activity. In contrast to the lighting response, this smoking related increase of heart rate disappeared for the last five as opposed to the first five cigarettes of the day, and it was also absent for ‘imaginary’ smoking without lighting.
Effects of nicotine on human psychomotor performance
Authors: Sherwood Neil
Published: December 2004

A comprehensive review was conducted to establish whether there were any grounds to the claim that nicotine can enhance human psychomotor performance. Among relevant studies, many failed to distinguish between absolute improvements due to the administration of nicotine (usually in the form of cigarettes) and the relief of the effects of nicotine abstinence among the preferred subject pool of tobacco smokers. However, a few investigations have avoided this anomaly by examining the effects of nicotine in minimally‐abstinent smokers or non‐smokers. The results of these studies suggest that nicotine has small, specific, positive effects on the central nervous system which may facilitate human attention, memory and sensori‐motor function.
Stabilization of psychophysical performance of healthy volunteers by propranolol—a contribution to differential psychopharmacology
Authors: Meyer Frank P. , Andresen K.
Published: December 2004

Eight volunteers out of 81 medical students of a one‐year register were selected in a two‐step procedure by means of a motivation Q‐sort. Of these, four were motivated for success (S.M.), whereas four were motivated for failure (F.M.). Following a stratification step, two subjects each from each group were orally given propranolol (0.6 mg/kg) or placebo in a double‐blind trial. Test inventory; flicker fusion frequency; determination performance in normal and tailored testing; subjective self‐rating; blood pressure; pulse. Evaluation was accomplished in the conventional dose‐related way (propranolol versus placebo) and in a serum level oriented approach common in differential psychopharmacology, by judging the personality structure (nervousness, neuroticism, extraversion) and the volunteers' motivation. It was found that propranolol when compared to placebo did not alter the vigilance, performance and subjective assessment of the volunteers; hence, the next step of evaluation was made regardless of the treatment. The initial performance of F.M. subjects as measured on the determination test unit was substantially poorer when compared to S.M. volunteers. During a 7.5‐h period after application, the reaction time of F.M. subjects was noted to improve both as a result of training due to repeated tests and as a function of propranolol. As only a small number of volunteers was available for the investigation, further studies are encouraged to verify performance of F.M. subjects.
Contrasting effects of midazolam and nitrous oxide on memory and cognitive bias in dentally phobic patients
Authors: File Sandra E. , Goodall Elizabeth M. , Sanders Fiona L. , Murray Alexandra , Skelly Ann M. , Joyce Eileen M. , Fluck Emma J.
Published: December 2004

Dentally phobic patients referred to the Guy's Sedation Unit and control dental patients were presented with lists of dentally related, general threat and neutral words. They were asked either to remember the words (superficial coding) or to rate them for liking (deeper coding). The control patients showed no significant bias in the words remembered, but the phobic patients attending for their assessment interview recognized more dentally related than neutral words, from both superficially and deeply coded lists. This bias was maintained over two tests and was not different for male and female patients or for those with high or low trait anxiety. On their first day of dental treatment phobic patients received lists both before and after receiving sedation with midazolam or nitrous oxide. These patients showed relative cognitive avoidance for dentally related words, but for the superficially coded words this was prevented by midazolam. In addition, midazolam caused significant amnesia for words presented after drug administration, for both the superficially coded list, and for the words presented for rating. Nitrous oxide significantly impaired recognition of the superficially coded words from the lists presented both before and after drug administration.
International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: I. Current concerns
Authors: Balter Mitchell B. , Ban Thomas A. , Uhlenhuth Eberhard H.
Published: December 2004

Although clinical experience influences psychotropic drug treatment world‐wide, it has been underutilized because it has not been systematically gathered and widely disseminated. An international survey was conducted to help remedy this situation. One of the major objectives was to develop a representative body of expert judgment and opinion on the clinical use of benzodiazepines in relation to other psychotherapeutic medications that might be used for the same purposes.

A select international panel of psychiatric experts on the pharmacotherapy of the anxiety and depressive disorders (N = 73) was constituted on the basis of progressive peer nominations. The peer selection process began with primary nominators from 44 countries. Judgments and opinions about psychotherapeutic medications were elicited from the Expert Panel via a self‐administered questionnaire. Completion rate: 90 per cent (66/73).

Outcomes bear directly on current therapeutic and regulatory concerns. Topics addressed include: special indications for use, abuse liability, dependence potential, duration of treatment, high‐risk treatments, and adverse effects. Although sometimes divided, agreement was generally high and indicative of a good benefit to risk ratio for the benzodiazepines. Expert judgments were more positive than would have been anticipated from media reports, public concern, and recent regulatory postures.

The following inferences can be drawn from this body of expert judgment and opinion: (1) qualitative differences in abuse liability among the benzodiazepines are minimal; (2) physical dependence at therapeutic doses is not a major clinical problem; (3) when physical dependence occurs, it can be readily managed clinically by the treating physician; (4) the relative abuse liability of the benzodiazepines as a class is low. These expert evaluations do not support or justify the imposition of stronger or differential restrictions on the benzodiazepines. The data help define the reasonable limits within which clinical guidelines and regulatory mandates can be meaningfully promulgated.
Dexamethasone‐induced growth hormone release: A dose‐response study
Authors: Thakore Jogin H. , Dinan Timothy G.
Published: December 2004

Glucocorticoids have recently been shown to acutely stimulate growth hormone secretion in man. The aim of our study was to investigate the acute effects of three graded doses of dexamethasone. Six healthy male volunteers received in random order placebo, 1, 2 or 4 mg of oral dexamethasone. Mean stimulated growth hormone levels were significantly higher after 2 and 4 mg of DEX than after 1 mg or placebo. We conclude that dexamethasone used in lower doses than previously reported appears to stimulate growth hormone release in a dose dependent manner.
Is a cut‐off score a suitable measure of treatment outcome in short‐term trials in depression? A methodological meta‐analysis
Authors: Angst J. , Delini‐Stula A. , Stabl M. , Stassen H. H.
Published: December 2004

In a meta‐analysis of short‐term (four weeks) trials of antidepressants, two response criteria were compared separately for low‐ (< 21), medium‐ (22–27) and high‐ (> 28) scores on the 17‐item version of the Hamilton Rating Scale for Depression: (HAMD‐17): (a) 50 per cent reduction of the baseline HAMD‐17 score and (b) 50 per cent reduction plus a cut‐off HAMD score of < 10. The material consisted of the data pool of comparative trials with moclobemide provided by Hoffmann‐La Roche, Basle.

The analysis showed that, on average, the HAMD‐17 scores decrease uniformly in all groups independently of the initial severity of depression. The percentage of score differences between high‐score, medium‐score and low‐score groups remained virtually unchanged over the whole observation period. Furthermore, the criterion combining a 50 per cent decrease with a cut‐off score of < 10 gives clear disadvantage for high‐scores to become responders since cases of severe depression require a much longer time to reach the threshold of 10 than do milder or moderately severe cases.

As to the question of evaluating differences between placebo and drugs, our analyses provided evidence that the simple criterion of 50 per cent reduction of baseline HAMD‐17 score is better suited to discriminate between placebo and drug responders in acute trials.
Fluvoxamine and sulpiride in comorbid obsessive–compulsive disorder and gilles de la tourette syndrome
Authors: George Mark S. , Trimble Michael R. , Robertson Mary M.
Published: December 2004

Recently interest has arisen concerning the genetic, pharmacologic and phenomenologic links between Gilles de la Tourette Syndrome (GTS) and Obsessive—Compulsive Disorder (OCD). Some theorize the two disorders may be phenotypic variations of the same neurobiologic defect. Previous studies have demonstrated serotonin (5HT) abnormalities in OCD patients and dopamine dysfunction in patients with tics and GTS. We probed the relationship between 5HT and dopamine in these disorders with a 14‐week, double‐blind, placebo‐controlled crossover trial of fluvoxamine (a specific 5HT reuptake inhibitor) versus sulpiride (a dopamine (D2) antagonist) followed by single‐blind combined therapy (4 weeks) in 11 subjects with comorbid OCD and GTS.

Sulpiride monotherapy significantly reduced tics and non‐significantly improved OC symptoms. Fluvoxamine, either alone or combined with sulpiride, non‐significantly ameliorated tics and reduced OCD symptoms. Additionally, tics and OC symptoms covaried. These results are consistent with a possible coupling of dopaminergic and 5HT systems in comorbid OCD/GTS subjects.
The effect of NMDA receptor antagonists on the neuroleptics‐induced catalepsy in mice
Authors: Maj J. , Rogóż Z. , Skuza G. , Sowińska H.
Published: December 2004

The effect of non‐competitive (MK‐801:/+/‐5‐methy‐10,11‐dihydro‐5H‐dibenzo [a, d] cyclohepten‐5,10‐imine hydrogen maleate) and competitive (CGP 37849: DL‐/E/‐2‐amino‐4‐methyl‐5‐phosphono‐3‐pentenoic acid) NMDA receptor antagonists on the catalepsy induced by neuroleptics in mice was studied. MK‐801 and CGP 37849 antagonized the catalepsy induced by haloperidol, spiperone and fluphenazine. (+)‐Cycloserine, a partial glycine agonist, reversed the anticataleptic effect of CGP 37849, but not that of MK‐801. The above results indicate that the anticataleptic activity of both these NMDA receptor antagonists is induced by an indirect activation of the dopamine system. The results provide further evidence that competitive NMDA receptor antagonists may be a new class of antiparkinsonian drugs.
Recent advances in paediatric psychopharmacology: A brief overview
Authors: Mirza K. A. H. , Michael A. , Dinan T. G.
Published: December 2004

Drug treatments for psychiatric disorders in children have always been a matter of controversy. During the past two decades psychopharmacologists have made considerable strides in establishing the efficacy and safety of existing drugs. Recent research has also generated new treatments whose practical benefits are yet to be established. This article presents a brief and selective overview of the current state of paediatric psychopharmacology.
The acute effects of smoking on heart rate and blood pressure: An ambulatory study
Authors: Jaquet Francine S. , Shapiro David , Uijtdehaage Sebastian H. J.
Published: December 2004

Under laboratory conditions smoking has been found to acutely increase blood pressure and heart rate in healthy subjects. Little is known about the short‐term effects of smoking under more naturalistic conditions when subjects are engaged in various activities. In this study, the short‐term effects of smoking on blood pressure and heart rate in natural settings were investigated in a group of healthy smokers. The degree to which these effects are moderated by other factors known to affect the cardiovascular system was investigated as well. Subjects (eight males, seven females) were dispatchers in the greater Los Angeles area. They wore an ambulatory blood pressure and heart rate monitor on two workdays for a total of 48 h. The present study confirmed that the acute effects of smoking on blood pressure and heart rate under natural conditions are similar to results from laboratory studies. Smoking acutely increased blood pressure and heart rate. Male and female smokers displayed similar cardiovascular reactivity to smoking. There was no indication of development of intraday tolerance. The acute action of smoking on blood pressure and heart rate was additive to the influence of posture on the cardiovascular system.
New synthetic membranes for dialysis. IV. A copolyether–urethane membrane system
Authors: Lyman Donald J. , Loo Bock H.
Published: December 2004

New dialysis membranes, prepared from linear block copolymers, have shown unique separation properties which appear to be based on definite solute–membrane interaction. The synthesis and characterization of block copolyetherurethanes based on poly (oxyethylene glycol) is described.
Blood flow and intravascular phenomena in the microvascular system
Authors: Nicoll Paul A.
Published: December 2004

Observations of microcirculatory blood flow in the wing membrane of the unanesthetized bat, Myotis leucifugus, show that many responses associated with the exposure of blood to foreign surfaces mimic normal behavior in these sites. The responses include leukocyte pavement formation, permeability changes, thrombus formation, and intravascular fibrin threads. Attempts to eliminate or suppress these reactions should recognize that they are latent normal physiological activities.
Heparin ionically linked to glass
Authors: Hersh L. S. , Weetall H. H. , Brown I. W.
Published: December 2004

Heparin has been ionically bonded to glass surfaces. The heparin coating resists fluid shear stresses as high as 104 dynes/cm2 at 30°C for periods in excess of 300 hr, and 1000 W of ultrasonic cleaning at 62°C for periods of more than 45 min. It also prevents the clotting of human blood.
Correlations between blood compatibility and heparin adsorptivity for an impermeable isotropic pyrolytic carbon
Authors: Bokros J. C. , Gott V. L. , La Grange L. D. , Fadall A. M. , Vos K. D. , Ramos M. D.
Published: December 2004

The influences of conditioning treatments and surface topography on the heparin adsorptivity and the thromboresistance of a high‐strength, impermeable, isotropic, pyrolytic carbon were investigated. The results of the adsorption studies indicate that the adsorption of heparin on such carbon surfaces is near the amount required for monolayer formation. The adsorbed heparin is rapidly elutriated in plasma. The heparin adsorption is not enhanced by a pretreatment with benzalkonium chloride. There was no relationship between the amount of heparin adsorbed on these materials and their compatibility with blood. Polishing, for example, which reduced heparin adsorption, enhanced the tromboresistance of these carbons, and while chemisorption of oxygen markedly reduced their thromboresistance, it did not influence the amount of heparin that could be adsorbed. In vivo tests showed that polished and outgassed, impermeable isotropic carbons deposited at low temperatures were significantly thromboresistant without the exogenous application of heparin. Examples of applications of these new materials in experimental valves are presented.
Electrochemical power sources for pacemakers: Electrocatalytic investigation of various oxygen cathodes using stainless steel anodes
Authors: Reynolds L. W. , Tye F. , Thronton C. , Srinivasan S.
Published: December 2004

Electrochemical cells consisting of stainless steel anodes and platinum black cathodes are attractive as power producers for cardiac pacemakers. The maximum power of these systems is of the right order. The electrocatalytic activity of various oxygen electrodes follows the same order in blood, as ascertained from in vivo studies, and in simple aqueous electrolytes. Subcutaneous implantation of the stainless steel anodes is preferable to intraperitonial insertion. The activity of a stainless steel anode is entirely due to its dissolution.
The significance of implant shape in experimental testing of biological materials: Disc vs. Rod
Authors: Wood Norman K. , Kaminski Edward J. , Oglesby Richard J.
Published: December 2004

Adult albino rabbits were implanted with 304 stainless steel discs and cylinders (rods) in the following sites: beneath periosteum of the anterior calvarium, under the masseter muscle of the left mandibular ramus and in the body of the sacrospinalis muscle. (1) The tissue reaction around the disc implants was compared with that observed around the cylinder implants through the study of histological sections. (2) The degree of reactions observed at the various sites was contrasted with that seen at the other sites. In all cases the muscle implants showed the greatest reaction. Discs showed many micro areas of tissue reaction randomly around their periphery. In contrast all the rod shaped implants in muscle showed a greater reaction towards the ends than in the mid portion of the shaft (clubbing) but rods implanted at other sites did not show this phenomenon. The results show that much of the histological tissue reaction seen around muscle implants is really caused by mechanical trauma which must be differentiated from a non‐compatibility reaction. It is important to choose a test site where mechanical trauma will be minimal (submasseteric site) and use an implant shape (discs) which will not produce clubbing.
The physiological effects of fluorocarbon liquids in blood oxygenation
Authors: Harris G. W. , Anderson R. M. , Defilippi R. P. , Nosé Yukihiko , Weber D. C. , Malchesky P. S.
Published: December 2004

The objective of this study was to determine the feasibility of using a fluorocarbon liquid in a liquid‐liquid contacting device for extracorporeal blood oxygenation. Extraction experiments were carried out wherein blood was gently contacted with FC‐43 (a fluorinated tributyl amine) for up to 48 hr. The fluorocarbon caused no significant change in red cell volume, white cell count, plasma hemoglobin, platelet count, plasma fibrinogen, or the relative amounts of thirteen different plasma proteins. To determine toxicity, FC‐43 slugs and emulsions were injected intravenously and intraaortically into dogs. No chemical toxicity has been found, but the fluorocarbon is intolerable above about 1.7 mg/kg because it retards the flow of blood through pulmonary capillaries. FC‐43 was used for several in vivo tests of a vertical cylindrical blood oxygenator. The hemolysis caused by the falling film of fluorocarbon on the inner Teflon wall of the cylinder was considerably less than that caused by direct contact between blood and Teflon, suggesting that the blood‐fluorocarbon interface is quite atraumatic. All these results indicate that this fluorocarbon liquid holds considerable promise for use in a liquid–liquid blood oxygenator.
Bio‐Compatibility in selection of materials for implantation
Authors: Homsy Charles A.
Published: December 2004

In this paper the factors which contribute importantly to incompatibility and functional failure of implant materials are examined. The interaction of these criteria in the etiology of implant failure is discussed in terms of the host response to an inert implant and the modulation of this response in the presence of cytotoxic sequellae. Cellular injury either of traumatic or biochemical origin is seen to stimulate sequestration of the offending implant by fibrous tissue. Difficulties associated with routine quantification of such response by animal implantation studies have led to development of rapid in vitro techniques to predict the quantity and cytotoxicity of moeities released by an implant. These techniques are based on infrared analysis and primary mammalian tissue culture with a pseudo body fluid to which materials are exposed at elevated temperature. The protocols allow formulation of rational criteria for rejection of candidate materials for clinical implantation and acceptance for definitive preclinical animal implant studies. The procedures are applicable for routine monitoring of materials accepted for fabrication of prototype or production implants and of fabricated prostheses.
An evaluation of polyelectrolyte complexes as biomedical materials
Authors: Marshall David W. , Cross Robert A. , Bixler Harris J.
Published: December 2004

Certain polyelectrolyte complexes have been developed which appear to be nonirritating to body tissues and do not initiate thrombus when in contact with the bloodstream.In vivotest results with animals are discussed salong with a description of the physical and chemical properties of the material. Methods of improving the mechanical properties of the complexes have been developed and illustrations of several simple biomedical devices are shown.
Surface microstructural factors and the blood compatibility of a silicone rubber
Authors: Nyilas E. , Kupski E. L. , Burnett P. , Haag R. M.
Published: December 2004

After early failures, a series of injection molded Silastic 372 (Medical Grade) Auxiliary Ventricle surfaces became implantable, under identical hemodynamic conditions, for 3–4 weeks with no formation of adherent thrombi. Improvement in blood compatibility is attributed to a preparative technology devised to eliminate various impurities and surface inhomogeneities found by physico‐chemical and electron microscopic techniques in Silastics which thrombosed rapidly in vivo. These imperfections were traceable to processing methods and/or resulted from properties inherent to the uncured elastomer. In addition to traces of molding cavity exudates, 2,4‐dichlorobenzoic acid, a decomposition product of the Silastic's peroxide catalyst can contaminate finished elastomers in amounts varying according to curing conditions. Sodium stearate solutions used to remove impurities were found to deposit microlayers which became irreversibly adsorbed as a result of transformation into stearic acid insoluble in neutral aqueous media. Aided by the lack of strong bonding between the filler and some of the Silastic's poly‐(dimethylsiloxane), certain molding conditions can expose silica particles in submicroscopical domains inducing clots. Demonstrated by electron micrographs and transmission sections, processing technology was found to affect the submicroscopic structure which can alter the compatibility of otherwise identical Silastics within wide ranges. These factors are recognized as important determinants of compatibility.
An evaluation of inert and resorbale ceramics for future clinical orthopedic applications
Authors: Hentrich R. L. , Graves G. A. , Stein H. G. , Bajpai P. K.
Published: December 2004

The compatibility of implanted ceramic materials with autogenous bone, and the subsequently noted influence of the ceramic on the rate of new bone formation, were investigated to evaluate such materials for use in orthopedic implants. Three ceramic materials, aluminium oxide (Al2O3), zirconium oxide (ZrO2), and calcium aluminate (yCaO · xAl2O3) were tested. These were placed in the femurs of rhesus monkeys for periods of 50, 100, and 350 days. Definite compatability between the autogenous bone and the materials was exhibited for the implant time periods evaluated. No toxicogenic activity was noted in any of the biochemical, biomedical, and ceramographic evolutions. An added benefit resulted from the calcium aluminate composition, which was fabricated as a two‐phase oxide material to make it slightly soluble in the body fluids. In the 50‐ and 100‐ day implants, the bone penetrated the ceramic for distances up to 100 μ while the ceramic dissolved and the pores enlarged. In addition, the mineralization in the area of the calcium aluminate was greater than that found around the other ceramics. Radiographs over the entire 350‐day implant period confirmed the increased callus formation around all of the materials with no signs of rejection evident in the surrounding osseous or soft tissues. After 350 days the entire pore area of the calcium aluminate ceramic was infiltrated with a columnar substance which on the basis of scanning electron microscope procedures was considered to be mineralized osteoid.
Lytic effects of plastic surfaces on erythrocytes
Authors: Dyck M. F. , Winters P. R.
Published: December 2004

Twenty‐one commercial plastics were exposed to 10% red blood cell suspension in buffered saline and their hemolytic effect was determined. The depression in surface tension of physiological saline solution exposed to the plastic surfaces was recorded and brought into relationship with their hemolytic behavior. It has been shown that both effects occur simultaneously. It is proposed to use the depression in surface tension of saline exposed to prospective plastic applicants as a bloodcindependent screening test for evaluation of plastics which are intended to be exposed to a cardiovascular environment.
Tolerance of modified poly(glycol methacrylates) by the organism
Authors: Barvič M. , Vacík J. , Lím D. , Zavadil M.
Published: December 2004

Investigation has been made of the short‐term tolerance of hydrophilic polymers on the basis of poly(hydroxy ethyl methacrylates) containing various amounts of acidic and basic groups. The worst tolerance was found with gels containing basic groups alone.
A device to study the degradation of blood in a shear field with controlled wall effects
Authors: Whiffen J. D. , Lightfoot E. N. , Dennis W. H. , Safford R. E. , Powaser M. M. , Solen K. A.
Published: December 2004

A technique is described for studying shear‐induced degradation of blood with near‐uniform shear exposure to walls of a single material. The device used is a specially designed coni‐cylindrical viscometer with essentially all blood‐contacting surfaces constructed of a single test material. The technique developed permits exposure of blood only to this material under such conditions that significant shear occurs only in the viscometric region of the device. Contact with air is prevented. Preliminary data are reported for blood taken from fasting dogs and tested in a prototype device constructed of polycarbonate (Lexan). Venous blood was found to hemolyze much more than arterial blood and the extent of hemotysis increased with time. Changes were also observed in the electrophoretic pattern of the plasma proteins.
Radiopaque denture base materials technic dentures
Authors: Chandler H. H. , Bowen R. L. , Paffenbarger G. C.
Published: December 2004

Technic dentures were made using composite base materials containing 30,40, and 50 weight % of a silance‐treated, readiopaque, powdered glass as the reinforcing filler and poly (methyl methacrylate) as the matrix. Dentures containing no glass were included for comparison. Molar‐to‐molar dimensional changes, effects of silance treatment fo the procelain teeth and handling and finishing characteristics were determined.

Dentures containing glass had less dimensional change during curing and subsequent water storage than those without glass. Thick upper dentrues exhibited the least change and thin lowers, the most. The Differences in the magnitudes of the changes would not be clinically noticeable.

Silance treatment fo the procelain teeth in thick upper dentures resulted in breakage of theposterior teeth in almost all instances. posterior teeth also freactured in thick upper dentures containing 40 and 50% of the silance‐treated glass even though the teeth were not treatedwith silance.

Mixing and molding properties of the composite materials, while acceptabgle, were slightly inferior to thematerial containing ono glass. Finiching characteristics were definitelyinferior in that it was more difficult and time‐consuming to attain the fial surfaces and these surfaces were not as smooth as smooth as those in dentures without glass.
Resorbable ceramic implants
Authors: Graves G. A. , Hentrich R. L. , Stein H. G. , Bajpai P. K.
Published: December 2004

The purpose of the investigation was to show the ability of two calcium aluminate ceramic compositions to act as suitable implants for partial replacements of long bones. It was anticipated from previous studies that the ceramic would be well tolerated by the autogenous bone and surrounding soft tissue while the ceramic was slowly dissolving in the body fluids, allowing new osseous tissue to penetrate the resulting pore structure. It was expected that after a period of time the ceramic would no longer exist as a separate entity but would be completely infiltrated with mineralized osseous tissue and ultimately be completely replaced by bone. Two ceramic implants were prepared by slightly different techniques and CaO to Al2O3 ratios. The result was a polyphase ceramic and a nearly single phase ceramic. The polyphase material, after implantation in the test subject for 32 weeks, was completely impregnated with connective tissue while undergoing considerable alteration in microstructure. The single‐phase material was not altered significantly in any way. This implant could not be fully evaluated for its ability to allow for osseous tissue formation on its surface, or within its open pore structure, due to slight variations in the original fixation of the implant and resulting attempts to correct the problems.