bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructural plasticity of the dentate gyrus granule cells following recurrent limbic seizures: I. Increase in somatic spines
Authors: Bundman Marsha C. , Pico Richard M. , Gall Christine M.
Published: May 2005

Various paradigms have been used to assess the capacity of the adult brain to undergo activity‐dependent morphological plasticity. In this report we have employed recurrent limbic seizures as a means of studying the effects of this form of enhanced neuronal activity on cellular morphology and, in particular, on the incidence of somatic spines on the dentate gyrus granule cells. Seizure activity was induced by the placement of focal, unilateral electrolytic lesions in the dentate gyrus hilus of adult rats. At various intervals postlesion, rats with behaviorally verified seizures were sacrificed, and the hippocampi contralateral, to the lesions were removed and prepared for electron microscopy. Quantitative analysis showed that as early as 5 hours postlesion there was a dramatic increase in the density and morphological complexity of spines on the perikarya of the granule cells in rats that received seizure‐producing hilus lesions when compared to granule cells from control rats. Many of the somatic spines received asymmetric synapses. The increase in somatic spines was dependent on seizure activity and persisted for at least 1 month following a single recurrent seizure episode. CA1 pyramidal neurons, which exhibit changes in gene expression in response to hilus lesion‐induced seizures but do not normally possess somatic spines, did not exhibit an activity‐dependent elaboration of somatic spines. Thus, the seizure‐induced elaboration of somatic spines represents an amplification of an existing feature of the granule cells and not an effect occurring throughout hippocampus. These data provide evidence for very rapid and long‐lasting structural plasticity in response to brief episodes of seizure activity in the adult brain. © 1994 Wiley‐Liss, Inc.
Effects of perforant path procaine on hippocampal type 2 rhythmical slow‐wave activity (theta) in the urethane‐anesthetized rat
Authors: Heynen Arnold J. , Bilkey David K.
Published: May 2005

Previous research has suggested that the entorhinal cortex plays a major role in the production of type 1 rhythmical slow‐wave activity (RSA) recorded in the hippocampus of the freely moving preparation. In the present experiment we investigated the contribution of the entorhinal cortex to the type 2 fields recorded under urethane anesthesia. Rats had stimulating electrodes and cannulae filled with procaine positioned in the perforant pathway of one or both hemispheres. Recording electrodes were positioned in the dorsal hippocampus of each hemisphere to record perforant path and commissural/associational evoked potentials and RSA fields. Following unilateral procaine blockade, a decrease in RSA amplitude was observed in the stratum oriens and fissure regions of both hemispheres. Concomitant with this change in RSA, there was a loss of perforant path evoked responses, although commissural/associational control potentials remained unaltered. A greater reduction in RSA amplitude was observed following bilateral procaine microinfusion. RSA phase reversal also occurred more dorsally in microelectrode depth profiles conducted through the hippocampus during perforant path inactivation. In current source density analyses performed under baseline conditions, large rhythmic sinks were observed in stratum oriens, in stratum radiatum, and in strata adjacent to the hippocampal fissure. A rhythmic source was often observed in stratum pyramidale. Following perforant path inactivation decreases in the magnitude of the phasic sinks located near the fissure and stratum radiatum were observed. In contrast to the reduction in RSA amplitude observed in the stratum oriens region, the sink in this region and the source in stratum pyramidale remained relatively unaltered. These results demonstrate that the entorhinal region contributes to the production of RSA observed under urethane anesthesia. Furthermore, the CSD and amplitude changes following perforant path inactivation suggest that a substantial portion of RSA recorded in stratum oriens may result from ventrally located RSA dipoles. © 1994 Wiley‐Liss, Inc.
Interhippocampal synthesis of lateralized place navigation engrams
Authors: Fenton André A. , Arolfo Maria P. , Nerad Ludek , Bures Jan
Published: May 2005

Rats were trained in a water maze in a dark room with the extramaze cues restricted to only dimly back‐lit shapes. We used lidocaine to reversibly lesion the dorsal hippocampus and this controlledcue room in order to examine interhippocampal synthesis of lateralized place engrams. Experiment 1 showed that lidocaine injected into both hippocampi effectively abolished place navigation for up to 25 min but not at 45 min. In experiment 2, each day under lidocaine blockade of one hippocampus, pretrained rats were trained in the water maze to locate the target according to two cues (e. g., AB). Two hours later, the contralateral hippocampus was inactivated and the rats were trained to the same location with two other cues (CD). On day 5, intact brain retrieval was tested in one of three conditions: ACQ (e. g., AB), one of the pairs of cues used in acquisition training; SYNTH (e. g., AC), one cue from each of the pairs used in acquisition; CONT (e. g., AE), one cue that was used in acquisition training and a novel cue. The results show that the hippocampi learned the two tasks independently and similarly [latency (L) at the asymptote = 7 s]. Retrieval performance was at the asymptote for ACQ (AB) and SYNTH (AC) (L = 6 and 7, respectively) but was disrupted for CONT (L = 12). In experiment 3 as in experiment 2, the rats were trained, under unilateral blockade, to a new place for 4 days. On day 5, retrieval with the trained hippocampus blocked was worse (L = 11) than with the untrained side blocked (L = 5). We conclude that interhippocampal synthesis of lateralized place engrams is automatic and highly efficient. © 1995 Wiley‐Liss, Inc.
Simultaneous blockade of non‐NMDA ionotropic receptors and NMDA receptor‐associated ionophore partially protects hippocampal slices from protein synthesis impairment due to simulated ischemia
Authors: Virgili Marco , Contestabile Antonio , Barnabei Ottavio
Published: May 2005

A large body of evidence exists to demonstrate that excitatory amino acids (EAA) and their receptors are involved in the pathophysiological mechanisms linking several acute brain insults, such as cerebral ischemia, to neuronal degeneration and death. Accordingly, the use of EAA receptor antagonists can be beneficial in attenuating or preventing the neuronal irreversible damage subsequent to various neuropathological syndromes. We have investigated the effect of 15 min of simulated ischemic conditions, i. e., oxygen/glucose deprivation, on hippocampal slices preparation measuring, as neurotoxicity indexes, both the amino acids efflux in the incubation medium, detected by HPLC, and the inhibition of protein synthesis, evaluated as 3H‐Leucine incorporation into proteins. Accumulation of neurotransmitter amino acids was measured in the medium during the “ischemic” period. Glutamate increased 30‐fold over the basal level while aspartate was sevenfold and GABA 12‐fold higher than in normal conditions. After a reoxygenation period of 30 min, the rate of protein synthesis of hippocampal slices subjected to “ischemia” was reduced to 35–50% of controls. The non‐competitive NMDA antagonist MK‐801 (100 μM) and the competitive NMDA antagonist CGP 39551 (100–250 μM) as well as the non‐NMDA receptor antagonist NBQX (100 μM) and AP3 (300 μM) were unable to counteract the metabolic impairment when they were present alone in the incubation fluid during simulated “ischemia.” An incomplete, but highly significant (p < 0.001), protection from protein synthesis impairment was achieved in the presence of an equimolar concentration (100 μM) of MK‐801 and NBQX. A similar protective effect could be reproduced using 100 μM NBQX in concomitance with a high Mg++ (20 μM) voltage‐dependent block of the NMDA receptor‐associated channel but not exposing the slices to a NBQX (100 μM) and CGP 39551 (100–250 μM) mixture. The recovery of protein synthesis in the presence of the MK‐801/NBQX effective combination was not paralleled by a detectable decrease in the amount of amino acids released in the incubation medium during the “ischemic” period. Taken together, the present data allow new insights into neurotoxicity‐mediating mechanisms, suggesting that multiple additive processes are involved and that antagonists acting at different sites on excitatory amino acid receptor subtype can show different neuroprotective potency. © 1995 Wiley‐Liss, Inc.
Effects of hippocampal lesions on spatial delayed responses in dog
Authors: Kowalska Danuta M.
Published: May 2005

Thirteen dogs were trained to perform spatial delayed responses to auditory cues in a three‐choice Nencki testing apparatus with a delay of 0 s and then 10 s with a criterion of 90% correct responses in 90 consecutive trials. Then six dogs received bilateral surgical removal of the hippocampus via the cortex of the suprasylvian gyrus (without additional injury to the entorhinal and parahippocampal cortex). Three dogs received control surgical ablation of the suprasylvian gyrus, which was damaged in ablation of the hippocampus, and four dogs served as intact controls. After the surgery or rest period, the dogs were tested for their retention (10‐s delay), and then they were given additional tests with extended delays (30, 60, and 120 s) and with distractions during the 60‐s delay period. In comparison with both control groups, dogs with hippocampal ablations had moderately impaired postoperative retention, as evidenced by the elevated numbers of errors on criterion. In subsequent stages of testing with extended delays, the impairment was greater and was significantly correlated with the extent of injury to the hippocampus. These data, together with an analysis of the animals' responses to the three‐choice situation, indicate that in dogs lesions of the hippocampus impair spatial memory. © 1995 Wiley‐Liss, Inc.
Input‐output relations in the entorhinal‐hippocampal‐entorhinal loop: Entorhinal cortex and dentate gyrus
Authors: Bartesaghi Renata , Gessi Tiziana , Migliore Michele
Published: May 2005

The pattern of impulse transfer along the entorhinal‐hippocampal‐entorhinal loop has been analyzed in the guinea pig by field potential analysis. The loop was driven by impulse volleys conducted by presubicular commissural fibers, directly stimulated in the dorsal psalterium, which monosynaptically activated perforant path neurons in the medial entorhinal cortex. Perforant path volleys activated in sequence the dentate gyrus, field CA3, field CA1, subiculum, and entorhinal cortex. Input‐output curves were reconstructed from responses simultaneously recorded from different stations along the loop.

The entorhinal response to the presubicular volley was found to increase gradually with respect to its input. The population excitatory postsynaptic potential (EPSP) of the dentate gyrus granule cells had a similar behavior. By contrast, the input‐output relation between the granule cell population spike and population EPSP was described by a very steep sigmoid curve. The population spike of CA3 and CA1 pyramidal neurons as well as the response evoked in the entorhinal cortex by the hippocampal output had slightly higher threshold than the granule cell population spike and, like the latter, abruptly reached maximum amplitude.

These findings show that the entorhinal‐hippocampal‐entorhinal loop transforms a linear input in a non‐linear, almost all‐or‐none output and that the dentate gyrus is the critical site where the transformation occurs. Beyond the dentate gyrus, the loop appears very permeant to impulse traffic. © 1995 Wiley‐Liss, Inc.
Two hundred years of dependence on antianxiety drugs
Authors: Olivieri Stefano , Cantopher Timothy , Edwards J. Guy
Published: May 2005

Dependence has developed in the case of each antianxiety drugs introduced into clinical practice during the last two hundred years. Throughout this time there has been a reluctance to accept that anxiolytics are drugs of dependence and this has led to prolonged delays in the recognition of the problem. New compounds have been used to treat addiction to older drugs, even after the new drugs themselves have been shown to be addictive. The limitations of existing methods of assessing addictive potential should be more widely recognised and patients treated with new antianxiety drugs should be monitored more intensely and for a sufficiently long period to decide definitely that the drug does not cause dependence. It is hoped that drugs free from addictive potential will one day be produced, but it is possible that dependence is an unavoidable price that has to be paid for having antianxiety drug in our pharmacological armamentarium.
The measurement of body sway
Authors: Coen R. F. , Neill G. K. , Lambe R. , Darragh A.
Published: May 2005

The reliability of a direct, contact, mechanical method for the quantification of body sway is assessed. Methodological aspects in measurement of the eyes open/eyes closed ratio are also considered.
Long‐term benzodiazepine treatment: Is it ever justified?
Authors: Chen Y. , Lader M.
Published: May 2005

Long‐term benzodiazepine treatment is still used for various indications. It is now accepted that benzodiazepines can cause dependence even in normal therapeutic doses in long‐term use. Is long‐term use therefore ever justified? This review marshals the evidence for and against the effectiveness of benzodiazepines in long‐term use and their side‐effects, especially psychological deficits. The topic of dependence is then addressed. It is concluded that although short‐term use is justified in view of the effectiveness and safety of the benzodiazepines, long‐term benzodiazepine use is much more problematic. In the absence of comprehensive long‐term efficacy and safety data, constant vigilance is necessary to prevent unplanned long‐term use.
Effects of repeated caffeine administration on cognition and mood
Authors: Loke Wing Hong
Published: May 2005

The effects of repeated caffeine administration on cognitive and mood tasks were investigated in a double‐blind study of 32 young healthy adults who were randomly assigned to one of the four treatment conditions: 0, 200, 400, or 600 mg of caffeine. Subjects were tested over six alternate days; on each test day they completed various tasks after drug administration. In general, caffeine produced no significant effects on cognitive performance; the exception is that the highest dose (600 mg) reduced the speed of completion of additions relative to the other doses. Also, post‐hoc analysis showed that the highest dose impaired performance of the lower caffeine users more than higher users. Mood assessment showed individuals were sensitive to the effects of caffeine but the effect did not interact with cognitive performance. The present data suggest that tolerance to the cognitive effects of caffeine does not develop with continued caffeine administration, given the limitations that the individuals tested were young healthy adults and the testing took place only over 2 weeks.
Tetrahydroaminoacridine in Alzheimer's dementia: Clinical and biochemical results of a double‐blind crossover trial
Authors: Åhlin A. , Nybäck H. , Junthe T. , Öhman G. , Nordgren I.
Published: May 2005

The cognitive decline in Alzheimer's disease has been shown to correlate with deficits in central cholinergic neurotransmission. Among various treatment attempts using cholinergic drugs a trial of the cholinesterase inhibitor tetrahydroaminoacridine (THA) (Summers et al., 1986) attracted considerable interest due to the positive effects reported on dementia symptoms. We have studied the effects of THA and placebo in a double‐blind crossover trial over 9 weeks in 15 patients with dementia of Alzheimer type. Doses of the drug (75–150mg/day) were titrated for each patient before entering the study. Clinical and biochemical effects were monitored using a battery of psychological tests, clinical rating scales and laboratory tests, including measurements of monoamine metabolites in the cerebrospinal fluid (CSF). The clinical results were mostly negative. Almost half of the patients had elevated liver enzymes (ALT and AST) in the THA period and these subjects showed more improvements of clinical ratings and psychological tests than did the patients without elevated liver enzymes. Levels of acetylcholine and the monoamine metabolites HVA and 5‐HIAA in CSF were elevated on THA. The results indicate that THA has a therapeutic potential, although its pharmacokinetic profile and its liability to induce liver damage may limit the clinical use of the drug in the future.
Interactions of smoking and lunch with the effects of caffeine on cardiovascular functions and information processing
Authors: Hasenfratz M. , Jaquet F. , Aeschbach D. , Bättig K.
Published: May 2005

Two experiments were done in order to verify earlier findings of caffeinic improvements of rapid information processing and to investigate possible interactive effects with smoking and eating. The first of these experiments investigated the interactive effects of caffeine and smoking a cigarette on rapid information processing (RIP), heart rate and blood pressure. Both treatments improved performance, but the effects were not additive. Heart rate increased as a consequence of smoking but not of caffeine. Both substances increased systolic blood pressure (SBP), and the effects were additive, while only caffeine increased diastolic blood pressure (DBP). The second experiment investigated in a similar paradigm the interactive effects of caffeine and a lunch. The lunch alone increased heart rate and decreased DBP, while it increased performance only slightly. Caffeine alone increased SBP, DBP and performance, but in combination with a lunch all three effects were dampened. Thus, these results confirm earlier findings of a facilitative effect of caffeine on information processing, and extend these observations to the behavioural states after a lunch and in combination with cigarette smoking.
Influence of nifedipine on human performance following a single dose—differential psychopharmacological aspects
Authors: Meyer F. P.
Published: May 2005

A motivation Q‐sort procedure was adopted in two screening steps to select from 92 medical students of a one‐year register 10 volunteers of whom five were motivated for success (S.M.) and five were motivated for failure (F.M.). The subjects were administered nifedipine (20 mg/subject, orally) or placebo in a double‐blind approach. Test inventory: Flicker fusion frequency, subjective self‐rating, d 2 cancellation test, tracking test. Classic evaluation of nifedipine vs placebo did not reveal any differences between the two treatments. In the next screening step, the subjects were stratified in respect of motivation and personality structure. This showed that, compared to placebo, extraverted, emotionally stable and S.M. subjects under nifedipine exhibited a more vigilant behaviour (CFF). Nifedipine was found to increase the inner tension of introverted, emotionally stable and F. M. subjects who had a poorer performance in the d 2 cancellation test. The problems ensuing from the small number of subjects available for the study are discussed. Still, it is felt that the differential approach is necessary.
Growth hormone responses to GABAB receptor stimulation throughout the menstrual cycle of healthy females
Authors: O'Keane Veronica , Dinan Timothy G.
Published: May 2005

Growth hormone (GH) responses to the GABAB agonist baclofen (10 mg) were assessed in six normally cycling, healthy women at three different sex steroid phases of the menstrual cycle: early follicular, pre‐ovulatory and luteal. The design was placebo‐controlled, balanced and single‐blind with a total of six tests being carried out on each subject in two consecutive menstrual cycles. GH responses to baclofen increased incrementally from early‐through mid‐ to late‐cycle: 10.95 ± 0.95 μg/l, 24.53 ± 4.73 μg/l, 31.36 ± 3.37 μg/l respectively (p < 0.04). Responses between early‐ and mid‐cycle and early‐ and late‐cycle were significantly different (p < 0.05). There was a direct relationship between baclofen/GH responses and both plasma oestradiol (E2) concentrations (p = 0.05) and plasma progesterone concentrations (p = 0.02). Responses to placebo did not vary. E2 has been demonstrated to exert a priming influence on GH responses to many pharmacological and physiological stimuli. An E2‐induced priming effect on GH secretion may underlie these results. Progesterone may augment this effect. Other possible influences are a sex steroid effect on somatostatin or GABA neurotransmission.
Self‐ratings by phobic patients during dental treatment: Greater improvement with nitrous oxide than midazolam
Authors: Goodall Elizabeth , File Sandra E. , Sanders Fiona L. , Skelly Ann M.
Published: May 2005

The efficacy of intravenous midazolam and nitrous oxide inhalation at reducing self‐rated mood and bodily symptoms was compared in patients referred to a dental sedation unit because their dental fears precluded treatment undrugged. Fifty‐eight per cent of our patients could be randomly allocated to drug treatment, the others were assigned on clinical grounds. When they arrived for their first treatment, the clinically allocated patients (n = 40) were significantly more anxious, tense and restless than those randomly allocated (n = 61). Both drugs reduced ratings of anxious, tense, discontented and restlessness, but the improvements were greater with nitrous oxide. Nitrous oxide reduced ratings of irritable and depressed, but patients treated with midazolam only showed reductions when dental treatment was finished. The scores for 70 patients were analysed over two treatment days; their pre‐sedation scores of tense, depressed and discontented were lower on day 2 than on day 1, with the randomly allocated group showing greater reduction. Nitrous oxide remained superior on day 2. Thirty‐eight patients completed 3 days of treatment; there were no further reductions in baseline ratings and the superiority of nitrous oxide was maintained.
The role of quality of life measures in psychopharmacology
Authors: Selai C. E. , Trimble M. R.
Published: May 2005

Despite the recent surge in interest in quality of life (QOL) measurement, surprisingly little attention has been paid to QOL in the field of psychopharmacology. Since psychopharmacology is a rapidly developing subject appraising the effect on overall QOL of new drugs is becoming increasingly important. The measurement of QOL in this area raises complex methodological issues; it is argued that there is a need for more QOL research in the field of psychopharmacology.
Autoradiographic distribution of cholinergic muscarinic receptors and serotonin2 receptors in olfactory bulbectomized (OB) rats after chronic treatment with mianserin and desipramine
Authors: Earley B. , Glennon M. , Lally M. , Leonard B. E. , Junien J‐L.
Published: May 2005

Bilateral removal of the olfactory bulbs in rats produces a behavioural abnormality that is defined by hyperactivity in the open‐field test. This abnormality may be related to depression since these behavioural effects can be attenuated by antidepressant drugs. Moreover, changes in the cholinergic and serotonergic system may be involved in the pathogenesis of depression. Thus, muscarinic cholinergic and serotonin2 receptors were measured by quantitative autoradiography after the bilateral removal of the olfactory bulbs from the rat. In OB rats, muscarinic receptor density was decreased in several brain regions including the amygdaloid cortex, the basal ganglia, hippocampus, hypothalamus, cortex and olfactory regions. Serotonin2 receptors were increased in all cortical regions, in the hippocampus and the thalamus. When OB rats were treated chronically for 35 days with mianserin (5 mg/kg i. p.) or desipramine (7·5 mg/kg i. p.) the behavioural hyperactivity was reversed and muscarinic receptor density was increased in the hippocampus and cortical regions while serotonin2 receptors were normalized. The results are consistent with a cholinergic and serotonin involvement in depressive illness and suggest that the cholinergic and serotonergic modulatory properties of antidepressant drugs may contribute to their therapeutic effectiveness.
The efficacy of cholinergic drugs in patients with Alzheimer's disease—focus on the aminoacridines
Authors: Siegfried K.
Published: May 2005

The article reviews evidence for the efficacy of the aminoacridines (tacrine, velnacrine) in patients with probable Alzheimer's disease (AD). The discussion revolves around the question of the clinical relevance of the treatment effects observed. Other questions discussed deal with the heterogeneity of the patient population having AD, the size of the potential reponder group and the limitations caused by safety problems of these compounds. The conclusion is that the effects of the aminoacridines appear to have clinical relevance in a subgroup of patients with AD. These compounds therefore truly deserve the label of ‘first‐generation AD agents’. But further basic and clinical research is needed to identify the responder group and predict response.
Evaluation of the development of acute tolerance to the psychomotor effects of midazolam following intravenous infusions in healthy volunteers
Authors: Fleishaker Joseph C. , Chambers James H. , Peters Gary R.
Published: May 2005

The effect on digit‐symbol substitution (DSST) of duration and extent of exposure to midazolam was studied in seven healthy male volunteers. Individual pharmacokinetic and pharmacodynamic parameters were estimated after a 7·5 mg intravenous bolus dose of midazolam. Subjects then received, in a double‐blind crossover design, loading doses of midazolam and steady‐dose infusions to provide (A) 25 per cent of maximal effect (Emax) for 6h, (B) 50 per cent of Emax for 3 h, (C) 75 per cent of Emax for 2 h, and (D) 0 per cent of Emax (placebo). Infusions A‐C were designed to yield a similar area under the effect curve (AUEC) during the infusion. DSST was assessed during the infusion and after a 3·75 mg IV midazolam challenge dose given at 6 h after infusion start. Actual decrements in DSST scores during infusions were 40·2 per cent, 60·7 per cent, and 86·8 per cent at 1 h for infusions A‐C, respectively. The degree of tolerance was assessed by calculating an effect ratio: ER = peak challenge dose DSST decrement/challenge dose Cmax. ER's for treatments A‐C and were 69·9 per cent, 79·3 per cent, and 68·4 per cent, respectively, of the control value; treatment A and CER's were significantly different from control. There were no significant differences among infusions A‐C in ER or AUEC. These results show that, in subjects who are relatively sensitive to the effects of midazolam, tolerance develops acutely to the effects of midazolam and suggest that tolerance is dependent on both the time and extent of exposure.
Platelet [3H]‐paroxetine binding in obsessive‐compulsive disorder
Authors: Maguire Kay P. , Norman Trevor R. , Apostolopoulos Maria , Judd Fiona K. , Burrows Graham D.
Published: May 2005

Platelet [3H]‐paroxetine binding was analysed in 26 patients (13F, 13M) with obsessive compulsive disorder and 26 normal controls (13F, 13M). For patients with obsessive compulsive disorder, Bmax was 2127 ± 480 fmol/mg protein (mean±SD) compared to control Bmax values of 1926 ± 696 fmol/mg protein. The mean Kd value for the patients was 0.075 ± 0.025 nM and for the controls was 0.076 ± 0.032 nM. Analysis of covariance indicated a significant effect of sex on both Kd and Bmax but no effect of diagnosis (obsessive compulsive disorder versus normal controls) or season of sampling. The data provide no evidence for an abnormality of the platelet uptake mechanism as assessed by the measurement of [3H]‐paroxetine binding to the platelet transporter in obsessive compulsive disorder.
Delirium during heroin withdrawal with doxepin: A short report
Authors: Barak Yoram , Levine Joseph , Lampl Yair , Elizur Avner
Published: May 2005

Doxepin was evaluated in a group of 10 patients for its efficacy in decreasing withdrawal symptoms during ambulatory heroin withdrawal. Although no subjective relief was reported by the subjects, during the 10 days trial, four of the patients developed full blown delirium during the trial's first three days. Since delirium is rarely one of the complications of heroin withdrawal the question whether doxepin enhanced or induced its appearance in these patients, remains unanswered.

Until this issue is resolved we suggest cessation of doxepin usage in the initial withdrawal phase from heroin.
Severe bradycardia following fluoxetine administration: A case report in a young HIV‐1 infected woman
Authors: Grassi Barbara , Gambini Orsola , Scarone Silvio
Published: May 2005

Some reports in the literature suggest that fluoxetine can produce bradycardia in elderly people or in subjects with cardiovascular diseases, thus indicating that the drug should be used with caution in this kind of patient. The aim of this case report is to notify that the same adverse effect could be found in HIV‐1 infected patients. The HIV‐1 infected patient we describe is a young woman not affected by cardiovascular pathologies who nevertheless developed severe bradycardia following fluoxetine administration. Therefore, we recommend caution not only when administering this drug to elderly people or subjects with cardiovascular diseases, but also to HIV‐1 infected patients.
The platelet intracellular calcium response to serotonin is augmented in bipolar manic and depressed patients
Authors: Berk Michael , Bodemer Wilhelm , Van Oudenhove Tania , Butkow Neil
Published: May 2005

The serotinergic system is widely implicated in the pathophysiology of affective disorder. In this study, basal levels of intracellular calcium as well as the effects of serotonin on intracellular calcium were studied in bipolar manic (N = 21), bipolar depressed (N = 19), bipolar euthymic (N = 20) and normal control (N = 20) subjects. At a serotonin concentration of 100 nm, there was an elevation in intracellular calcium readings, with the highest mean levels in the manic group (158·6, SD = 105·1) followed by the depressed (140·6, SD = 76·4), controls (122·8, SD = 61·6) and the euthymics (96·2, SD = 31·0). The difference between manics and euthymics reached statistcal significance (P = 0·0181) using pooled variance, as did the difference between depressives and euthymics (P = 0·0238). Similar results were found at the 500 nm and 1 μm levels of serotonin. This suggests that an enhanced serotonin mediated mobilization of intracellular calcium occurs in patients in both the manic and depressive phases of bipolar disorder, and may be an index of second messenger dysregulation secondary to hypersensitivity of the platelet 5HT2 receptor. In addition, the results suggest that this is a state marker of bipolar disorder.
Relapse after successful electroconvulsive therapy: The use and impact of continuation antidepressant drug treatment
Authors: Riddle William J. R. , Scott Allan I. F.
Published: May 2005

Thirty eight (76 per cent) of a series of 50 depressed patients routinely referred for bilateral electroconvulsive therapy (ECT) improved markedly by two weeks after the last ECT. Patients remained under the care of their responsible clinicians after ECT. Only one‐third of the patients who improved markedly were prescribed continuation antiddepressant drug treatment for at least four months after ECT. Seventeen (46 per cent) of the patients who improved relapsed within six months of the last ECT. Patients who did not receive continuation antidepressant drug treatment were four times more likely to relapse (the 95 per cent confidence interval of the excess relapse rate was 24 to 78 percent).
The impact of sertraline, desipramine, and placebo on psychomotor functioning in depression
Authors: Ravindran A. V. , Teehan M. D. , Bakish D. , Yatham L. , O'Reilly R. , Fernando M. L. , Manchanda R. , Charbonneau Y. , Buttars J.
Published: May 2005

Impairment of psychomotor performance is a common adverse effect of many antidepressants, particularly tricyclics. Desipramine is thought to be an exception, with possible performance enhancing effects on psychomotor function. This multicentre study examined the relative effects on psychomotor function of sertraline versus desipramine versus placebo in mild to moderate depression.

Fifty‐eight patients who satisfied DSM‐III‐R criteria for major depression and had a minimum HAM‐D score of 15 (17 items) completed eight weeks of treatment. They underwent a standardized assessment which included depression and anxiety rating scales (HAM‐D, HAM‐A, MADRS) and a battery of psychomotor performance tests (The Simple and Choice Reaction Time, The Digit Symbol Substitution and The Trail Making Test), before, during, and after eight weeks of treatment with sertraline, desipramine, or placebo.

At baseline, there was a trend for both the sertraline and placebo groups to exhibit better psychomotor performance than desipramine. No significant differences were found between groups after treatment nor between groups for the change from baseline to week 8. However, at week 3, the sertraline group performed significantly better in the trail making test than the placebo patients (p<0.05). Within each treatment group, there was a trend towards improvement in performance for all four parameters from baseline to the end of the study, with these improvements being most obvious in the desipramine group. Sertraline, however, was found to be associated with significantly fewer other adverse effects than the desipramine group, i.e. sweating, dry mouth, anorexia.

These results suggest that desipramine and sertraline do not adversely affect psychomotor performance and may even enhance it in mild to moderately depressed patients.
A naturalistic study in the use of antidepressants in adults with learning disabilities and affective disorders
Authors: Bhaumik S. , Collacott R. A. , Gandhi D. , Duggirala C. , Wildgust H. J.
Published: May 2005

Very few studies have been undertaken looking at the use of anti‐depressants in adults with learning disabilities and, more recently, with the advent of SSRIs there has not been any study comparing the use of SSRIs with tricyclic drugs in this group. A naturalistic study involving adults with learning disabilities suffering from depressive illness was undertaken in Leicestershire that included 104 treatment episodes with tricyclic/tetracyclic groups of drugs and SSRIs and issues related to efficacy, tolerability, side‐effects, polypharmacy and discontinuation rates were looked at. The study, despite its limitations, establishes for the first time that depressive illness in patients with learning disabilities does respond to antidepressant treatment in the same way as that of the general population. The findings suggest that SSRIs are better tolerated and present with fewer serious side effects when compared to tricyclic/tetracyclic groups of drugs. The efficacy of both groups of drugs was found to be very similar. This study also highlights that SSRIs are reasonably safe to use in conjunction with drugs like Lithium and Carbamazepine.
Psychoimmunoendocrine aspects of panic disorder
Authors: Perini G. I. , Zara M. , Carraro C. , Tosin C. , Gava F. , Santucci M. G. , Valverde S. , De Franchis G.
Published: May 2005

Stress‐responsive neurohormonal systems are involved in major depression (MD) and panic disorder (PD). The immune system, which is closely connected with neuronal and hormonal systems, has been studied in MD: a systemic immune activation has been recently reported. To determine whether similar changes in the immune function are present also in PD, we studied leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining, in 18 PD, 23 MD in drug‐free conditions and 20 controls. We found a significantly higher percentage of HLADR + (p <0·001) and of CD 19 cells (p < 0·01) in PD and MD and a lower percentage of CD3 (p < 0·05) in PD. Urinary free cortisol levels were higher in MD compared to PD. A pattern of lymphocyte subpopulation distribution compatible with an activation of the immune system was found in MD and PD. This activation was present also with high glucocorticoid levels, suggesting a possible defect of glucocorticoid receptors.
In vivo evaluation of 2‐cyanoacrylates as surgical adhesives
Authors: Tseng Yin‐Chao , Hyon Suong‐Hyu , Ikada Yoshito , Shimizu Yasuhiko , Tamura Koichi , Hitomi Shigeki
Published: May 2005

To evaluate 2‐cyanoacrylates as surgical adhesives, the bond strength in vivo as well as the tissue reaction was investigated using methyl‐, ethyl‐, isobutyl‐, and ethoxyethyl‐2‐cyanoacrylate. In addition, their set time and spreading on blood were studied. When the 2‐cyanoacrylates were applied to an incised site of rabbit skin, they could maintain the skin closure without suturing during the first week and the bond strength increased during the second week. Significant inflammatory response was observed around the subcutaneous tissue glued with methyl‐ and ethoxyethyl‐2‐cyanoacrylate and persisted for approximately one week. All the 2‐cyanoacrylate polymers were absorbed and the tissues treated were healed two weeks after the operation. There was a mild inflammatory reaction in the tissue treated with ethyl‐ and isobutyl‐2‐cyanoacrylate, and their polymers still remained at the wound site at the second week postoperatively. The disappearance rate of the 2‐cyanoacrylate polymers was roughly in proportion to the inflammatory tissue response. Ethoxyethyl‐2‐cyanoacrylate spread more broadly on tissues than the other 2‐cyanoacrylates, while its set time was shorter than that of methyl‐ and ethyl‐2‐cyanoacrylate.
Patent literature as a source of information for research and development: An investigation on calcium phosphate‐containing biomaterials, Part II
Authors: Wüstefeld M. , de Groot K.
Published: May 2005

After the first approach to patent literature in a scientific library (Part I), we have completed the patent retrieval on the mentioned subject with the facilities of patent collections. This work describes the various methods: the direct access to original documents with classification codes, the consultation of the secondary literature of official gazettes and private services, and the use of indexes. The application of all these methods concerning calcium phosphate‐containing biomaterials is presented and discussed. The retrieval resulted in 363 applications during the period 1975–1985 and 134 in 1986. Forty‐nine percent and 63%, respectively, of these applications were basic patents, the rest were equivalents. The technical information which 80% of all these documents contain has already been indexed in Chemical Abstracts. The remaining documents are only available in patent collections. They deal with more technical problems and concentrate in specific IPC groups. Because of the language barrier, the access to Japanese patents is often only possible by means of equivalent patents applied in the United States, Great Britain, the Federal Republik of Germany or international authorities (EPO, WIPO). These are filed up in patent collections.
Long‐term delivery of testosterone by ALCAP ceramic implants in rats
Authors: Benghuzzi Hamed A. , Bajpai Praphulla K. , England Barry G.
Published: May 2005

The capability of ALCAP ceramic drug‐delivery implantable devices to release testosterone for 12 months was investigated. A total of 120 Sprague‐Dawley male albino rats were distributed equally into three groups. Two ALCAP capsules, one nonimpregnated and the other impregnated with polylactic acid (PLA) were implanted into each rat in Groups I and II. Capsules implanted into Group I rats were loaded with 40 mg testosterone (T) each. Group II rats were implanted with two empty capsules (sham group), and Group III animals served as unimplanted controls. Eight rats from each group were euthanized at the end of 1, 3, 6, 9, and 12 months following the implantation of the ceramics. No significant changes in the weights of vital organs of rats were observed between any of the three different groups. Vas deferens and epididymal fluid were devoid of normal spermatozoa within 3 months of implanting the steroid‐containing ceramics. Testes and epididymis weights decreased significantly in the rats implanted with ALCAP ceramics containing steroid, and the seminiferous tubules became oligospermic after 1 month and azoospermic after 3 months. Circulating levels of both LH and FSH hormones were suppressed in experimental rats. Serum T level was lower than the control but showed no significant difference in comparison to control rats. The data collected in this study suggest that: (a) ALCAP ceramic capsules are capable of delivering T in a sustained manner for 12 months; (b) T delivered by ALCAP capsules can be used effectively to regulate spermatogenesis in rats.
Preliminary development of a hydroxyapatite‐backed strain gauge
Authors: Szivek J. A. , Gealer R. G. , Magee F. P. , Emmanual J.
Published: May 2005

Long‐term in vivo strain sensing would provide information about deformation changes adjacent to implants during bone remodeling. Biodegradation of the cyanoacrylate adhesive commonly used to attach strain gauges to bone has generally limited in vivo strain sensing to time periods less than one month.

Hydroxyapatite (HA) which has been used to attach implants to bone in vivo, was attached to strain gauges using a solvent‐thinned polysulfone solution. Three HA‐polysulfone surface morphologies were tested in a preliminary bench‐top test. The single layer pressed surface morphology, which responded most accurately during bench‐top testing, was modified slightly and applied to two gauges which were implanted on the femur of a greyhound.

Strain measurements from the HA‐backed gauges in place for four months in vivo were compared to strains measured from the contralateral femur. Comparison of the results indicated these gauges were well‐bonded and that they were sensing strain accurately. After embedding in PMMA, the femur having the HA‐backed gauge and the control femur were sectioned at the level of one of the HA‐backed gauges, Microradiographs of these sections indicated no adverse tissue response to the HA‐backed gauge on the endosteal or periosteal surface.
Applied biomaterials standards report
Authors: Daniels A. U. “Dan”
Published: May 2005

The purpose of my column is to provide readers with current information on biomaterials‐related standards produced by both private groups and government agencies, and standards‐related activities. Standards are descriptive documents given official status by their producers, and in the case of biomaterials, they are generally intended to provide formalized descriptions of (a) materials used in the construction of medical devices, (b) materials used directly in surgical repairs, (c) test methods to evaluate materials for such applications and (d) methods for handling or processing such materials.

Please consider this column not only a place to obtain biomaterials standards information but also a place to submit news of biomaterials standards developments in order to get the information before the public. This invitation extends to members of all professional organizations and government agencies in the United States and abroad who are active in standards development and would like specific activities or standards publicized. I will present the information in this column to the extent that allotted space allows.

And last, a caveat—since this is a column, it contains both factual information and opinions. I will make every effort to make it clear which is which. Also, as a frame of reference, please note that this column was written and submitted in June 1990.
Histological and ultrastructural observations at the interface of expanded polytetrafluorethylene anterior cruciate ligament implants
Authors: Müller‐Mai C. M. , Gross U. M.
Published: May 2005

Anteior cruciate ligament (ACL) grafts made from expanded polytetrafluorethylene (ePTFE) were examined after failure (n = 7; 3 instabilities, 2 partial and 2 complete ruptures) to provide information about secondary fixation mechanisms via ingrowth of the different tissues. The ultrastructural evaluation clearly evidenced the existence of two main interface areas of ePTFE ACL‐replacement: First, in areas without a dense cellular infiltrate there was interdigitating collagen producing a dense ePTFE‐collagen network. Additionally, in a few areas of the graft/bone‐tunnel interface a fibrous cartilage or bone regenerate could be demonstrated to be in contact with the prosthesis. Second, there was a dense infiltration of macrophages and multinuclear giant cells, partially containing birefringent material of implant origin, with and without a neosynovia‐like reaction product, indicating a disturbance of tissue integration of the prosthesis. In areas of inflammation there was no bone development and only few collagen interdigitation with the graft material. This study provides further knowledge about mechanisms of secondary graft fixation due to tissue ingrowth. The interdigitation of collagen fibers and ePTFE filaments provides interfaces which should be at least partially resistant against load.
Plasticizer permeation across mucosal tissue: An experimental and theoretical study
Authors: Pink David A. , Foong Wai‐Choong , Jones Derek W. , Gates Kimberly A. , Mezei Micheal , Farrell Kevin
Published: May 2005

In vitro transmucosal permeation of (14C)‐dibutyl phthalate [(14C)DBP], across intact mucosal hamster tissue compared to keratin‐stripped mucosal tissue indicated no significant difference (p ≈ 0.069) in (14C)‐DBP. However, significantly greater (p < 0.022) DBP was found to be concentrated in the keratin‐stripped after a period of 6 h. The amount of (14C)‐DBP permeating both tissues followed a similar linear increase for next 3 h. However, between 3 and 4 h, the rate of permeation through the untraumatized tissue significantly decreased. This was followed by a rapid linear increase for the next 3 h. In contrast, the cumulative amount of (14C)‐DBP permeating the traumatized tissue showed a linear correlation (r = 0.995) over the 6‐h period. A theoretical two‐layer model was constructed to allow computer simulations of the (14C)‐DBP permeation. It was indicated that an average diffusion coefficient for a single DBP molecule through the intact keratin layer would be ∼ 100 times less than through the remaining layer of the model. The model has enabled a possible explanation to be put forward, describing the role of the keratin layer in the permeation of plasticizer mucosal tissue.
Lattice defects in calcium phosphate ceramics: High resolution TEM ultrastructural study
Authors: Daculsi G. , Legeros R. Z. , Legeros J. P. , Mitre D.
Published: May 2005

Ultrastructural properties of precipitated apatites were characterized before and after sintering at 900 and 1250 °C using high resolution transmission electron microscopy. The apatite crystals were oriented with respect to the electron beam so that the crystals could be examined in relation to the high resolution images of the (001) and (100) planes. The ultrastructural properties were found to be affected by sintering temperature. Numerous lattice defects, including atomic vacancies, dislocations and two types of grain boundaries were observed. In addition, a new type of three‐dimensional lattice defect was frequently observed in the apatites sintered at 900 °C. This type of lattice defect has the character of a hexagonal parallelipiped void, probably resulting from an aggregation of atomic vacancies. Calcium phosphate ceramics (hydroxyapatite and tricalcium phosphate) prepared by precipitation and subsequent sintering to temperatures above 1100 °C are presently used as bone grafts. The amount and kind of defects such as those observed in this study have significant implications on the extent of the degradation of these materials in vivo.