bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐lasting effects of partial hippocampal kindling on hippocampal physiology and function
Authors: Stan Leung L. , Zhao DiChen , Shen BiXia
Published: May 2005

The objective of this project was to study the behavioral and physiological effects at 6–9 weeks after evoking 15 afterdischarges (ADs) in hippocampal CA1 (partial hippocampal kindling). Rats were trained on the open radial arm maze (RAM) with all eight arms baited, kindled, and then tested again on the RAM, followed by in vitro recordings at 8–9 weeks after kindling. Partial kindling was manifested by an increase in hippocampal AD duration. Enhancement of the commissural basal dendritic excitatory postsynaptic potential (EPSP) was observed for at least 1 day after the ADs kindled rats performed worse than control rats during the 1st but not during the 7th or 8th week after kindling. Rats that were slow in acquiring the RAM showed more RAM errors after kindling than those that showed fast acquisition. At 8–9 weeks after kindling, as shown by field potential recording in the hippocampal slice in vitro, kindled rats showed an increase in paired‐pulse facilitation (PPF) of the EPSP in CA1 but a decreased PPF of the perforant path to dentate gyrus EPSP; no change in the PPF of the population spike was found in CA1 or DG. In a second group of rats that were not run on the RAM, at 6 weeks after kindling, PPF of the population EPSP and population spike were enhanced in the kindled rats compared to the control rats in CA1, but not in DG or CA3 in vitro (at 1.5, 2, or 4 times threshold intensity). In conclusion, partial hippocampal kindling induced persistent physiological effects for up to 8–9 weeks, and it is suggested that the normalization of the paired‐pulse population spike response in CA1 and DG at more than 6 weeks after kindling may be accompanied by a recovery of RAM performance. © 1994 Wiley‐Liss, Inc.
Dentate gyrus destruction and spatial learning impairment after corticosteroid removal in young and middle‐aged rats
Authors: Conrad Cheryl D. , Roy Edward J.
Published: May 2005

We investigated the functional and behavioral implications of chronic corticosteroid removal in young and middle‐aged rats. Prepubertal and 13‐month‐old rats were adrenalectomized (ADX) or sham operated (SHAM). The young ADX rats were divided further into three groups: ADX with no hormone replacement, ADX given corticosterone chronically, (chCORT), and ADX given corticosterone acutely at the time of Morris water maze testing (acCORT). All rats were run on the Morris water maze 12 weeks after surgery. They were then sacrificed and the brains were removed for histological analysis.

The results showed that prolonged corticosteroid absence caused major damage to the dentate gyrus and learning impairment on the Morris water maze. The chCORT rats had little dentate gyrus cell loss and were as efficient as the controls in Morris water maze performance, whereas the acCORT rats had dentate gyrus cell loss and were impaired in the spatial acquisition task. Furthermore, exogenously administered corticosterone had an interactive effect on ADX rats. Water maze performance was improved in dentate gyrus damaged rats (acCORT) compared to ADX rats not given corticosterone, whereas ADX rats with very little dentate gyrus damage (chCORT) did not exhibit better water maze performance relative to controls. Middle‐aged ADX rats lost cells only in the dorsal blade of the dentate gyrus but they did not show a learning impairment in the Morris water maze relative to the middle‐aged controls. These results indicate that corticosteroids are trophic for the dentate gyrus, that mature granule cells are less affected by adrenalectomy, that corticosteroid absence is responsible for some water maze impairment in ADX rats, but that in addition to corticosteroid absence, a substantial amount of dentate gyrus damage is necessary to impair spatial learning. © 1995 Wiley‐Liss, Inc.
Activation of somatostatin‐synthesizing neurons in the hippocampal formation through kindling‐induced seizures
Authors: Pretel S. , Applegate C. D. , Piekut D. T.
Published: May 2005

The present study was designed to determine if and to what extent somatostatin (SST) synthesizing neurons of the hippocampal formation are activated during seizures, elicited through kindling of the perforant pathway. Tissue was used and analyzed from animals which had experienced a single afterdischarge, or a stage 3 or stage 5 seizure. The protein expression of the oncogene c‐fos in activated, depolarizing neurons was utilized to identify seizure‐activated SST‐synthesizing neurons. Combined immunocytochemical and in situ hybridization methods were used to identify these double‐labeled, Fos protein, and SST mRNA‐containing neurons. The results were quantified and compared across seizure stages. The resulting data demonstrate that at every stage of seizure development, a majority of SST‐synthesizing neurons is activated, but that these activated SST mRNA‐containing neurons represent only a minority of all seizure‐activated, Fos‐expressing neurons in the hippocampal formation. The data further reveal a numerical hierarchy in which the majority of double‐labeled neurons is present in the hilus of the dentate, followed by the stratum oriens of CA1. It is concluded that SST‐synthesizing neurons represent an integral component of the kindling activated neuronal network and, since the SST synthesizing neurons represent the minority of all seizure‐activated neurons in the hippocampal formation, that this neuronal network is likely to be of considerable neurochemical complexity. & 1995 Wiley‐Liss, Inc.
Intracellular correlates of hippocampal theta rhythm in identified pyramidal cells, granule cells, and basket cells
Authors: Ylinen Aarne , Soltész Iván , Bragin Anatol , Penttonen Markku , Sik Attila , Buzsáki György
Published: May 2005

The cellular‐synaptic generation of rhythmic slow activity (RSA or theta) in the hippocampus has been investigated by intracellular recording from principal cells and basket cells in anesthetized rats. In addition, the voltage‐, coherence‐, and phase versus depth profiles were examined by simultaneously recording field activity at 16 sites in the intact rat, during urethane anesthesia, and after bilateral entorhinal cortex lesion. In the extracellular experiments the large peak of theta at the hippocampal fissure was attenuated by urethane anesthesia and abolished by entorhinal cortex lesion. The phase versus depth profiles were similar during urethane anesthesia and following entorhinal cortex lesion but distinctly different in the intact, awake rat. These observations suggest that dendritic currents underlying theta in the awake rat may not be revealed under urethane anesthesia.

The frequency of theta‐related membrane potential oscillation was voltage‐independent in pyramidal neurons, granule cells, and basket cells. On the other hand, the phase and amplitude of intracellular theta were voltage‐dependent in all three cell types with an almost complete phase reversal at chloride equilibrium potential in pyramidal cells and basket cells. At strong depolarization levels (less than 30 mV) pyramidal cells emitted calcium spike oscillations, phase‐locked to theta. Basket cells possessed the most regular membrane oscillations of the three cell types. All neurons of this study were verified by intracellular injection of biocytin. The observations provide direct evidence that theta‐related rhythmic hyperpolarization of principal cells is brought about by the rhythmically discharging basket neurons. Furthermore, the finding that basket cells were also paced by rhythmic inhibitory postsynaptic potentials during theta suggest that they were periodically hyperpolarized by their GABAergic septal afferents. & 1995 Wiley‐Liss, Inc.
Information acquired by the hippocampus interferes with acquisition of the amygdala‐based conditioned‐cue preference in the rat
Authors: McDonald Robert J. , White Norman M.
Published: May 2005

White and McDonald (1993, Behav Brain Res 55:269–281) previously reported that animals with amygdala lesions failed to acquire a conditioned‐cue preference (CCP) based on spatial cues, but that animals with fornix lesions exhibited larger CCPs of this type than normal animals. The present experments focused on the hippocampal interference with amygdala‐based CCP learning inferred from this finding. In experiment 1 we tested the hypothesis that this interference was due to the acquistion of information about the maze and its environment during a 10 min period of free exploration of the maze before the start of CCP training, hitherto given to all animals in these experiments. Normal animals that were not preexposed to the maze and animals that were preexposed to similar maze in a different room both exhibited larger CCPs than animals that were preexposed to the same maze in the same room as CCP training and testing. This suggests that normal animals acquire context‐specific information during the preexposure period and that this may be the cause of the hippocampus‐based interference with the amygdala‐mediated CCP. In experiment 2 we attempted to determine if the information thought to be acquired by the hippocampal memory system interferes with acquistion or expression of the CCP. As previously demonstrated, animals that received fornix lesions before preexposure (i.e., before the start of the experiment) exhibited larger than normal CCPs. Animals that received fornix lesions after preexposure but before CCP training and animals that received fornix lesions after CCP training but before testing both exhibited normal CCPs. These findings suggest that a hippocampally mediated process acts via a pathway that does not involve the fornix to inhibit either acquistion or expression, or both, of the CCP. These results imply the existence of some form of competition for behavioral control among neural systems that may be specialized for acquiring different types of information about the same situations. © 1995 Wiley‐Liss, Inc.
Evidence for physiological growth of hippocampal mossy fiber collaterals in the guinea pig during puberty and adulthood
Authors: Wolfer David P. , Lipp Hans‐Peter
Published: May 2005

By means of Timm's procedure and computer‐assisted morphometry, the left and right hippocampi of 69 hybrid guinea pigs from nine age levels (P5, P10, P20, P40, P80, P160, P320, and P610, and P1100) were analyzed for postnatal growth of recurrent hippocampal mossy fiber collaterals (RMFC) terminating below, within, and above the dentate granule cell layer. Postnatal growth of RMFCs showed, in both sexes, a first peak at P40, with stainable mossy fiber boutons covering the cell bodies of large neurones, some of which were reminiscent of basket cells. No significant changes of the density of mossy fiber collaterals were noticed from P40 to P160. At P320 a remarkable expansion of RMFCs was noted in a few animals, and by P610 all animals showed highly proliferated RMFCs which densely covered cell bodies and dendrites of target cells. The oldest group (P1100) showed an equal or slightly lowered density of RMFCs.

We conclude that the growth of recurrent mossy fiber collaterals occurs in two spurts. The first completes just before sexual maturity. The second spurt occurs in the mid‐life period, between P160 and P610. © 1995 Wiley‐Liss, Inc.
AMPA‐selective glutamate receptor subtype immunoreactivity in the hippocampal formation of patients with Alzheimer's disease
Authors: Ikonomovic Milos D. , Sheffield Roxanne , Armstrong David M.
Published: May 2005

Immunocytochemical techniques were employed in order to examine the distribution and relative intensity of the AMPA receptor subunits GluR1 and GluR2/3 within the hippocampal formation of normal controls and Alzheimer's disease (AD) cases. Throughout our investigation we examined cases exhibiting a wide range of pathologic severity, thus allowing us to correlate our immunohistochemical data with the extent of pathology. Specifically, we investigated the distribution of these receptor subunits in hippocampal sectors that are particularly vulnerable to AD pathology (i. e., CA1 and subiculum) and compared these findings with those obtained following examination of sectors that are generally resistant to pathologic change (i. e., CA2/3, dentate gyrus). Within vulnerable sectors we observed a variable loss of GluR1 and GluR2/3 immunolabeling. The degree to which these proteins were reduced appeared to correlate with the extent of neurofibrillary pathology and cell loss. Despite the loss of labeled cells, the intensity of immunolabeling within the remaining neurons was comparable with, and in many instances even greater than, that observed in control cases. Within resistant sectors, the distribution of immunoreactive elements was comparable in both case groups yet the intensity of immunolabeling was markedly increased in AD cases, particularly in the molecular layer of the dentate gyrus and in the stratum lucidum of CA3 (i. e., the termination zones of perforant pathway and mossy fibers). In addition, within AD cases dramatic increases were observed within the supragranular and polymorphic layer of the dentate gyrus (i. e., the terminal zones of sprouting mossy fiber collaterals). The increase in GluR1 and GluR2/3 immunolabeling is hypothesized to occur in response to the deafferentation of selected glutamatergic pathways. Moreover, our data support that hippocampal plasticity is preserved, even in severe AD cases, and suggest a critical role for AMPA receptor subunits in this plasticity and in maintaining hippocampal functioning. © 1995 Wiley‐Liss, Inc.
Caffeine: Clinical and experimental effects in humans
Authors: Bruce M. S. , Lader M. H.
Published: May 2005

The contrast of attitudes to the psychiatric effects of caffeine between North America and Britain is highlighted. A summary of the dietary sources, pharmacology and effects of caffeine on normal subjects is given. The emphasis in normal subjects is on the acute, chronic, toxic and withdrawal effects. With this background information, a more specific evaluation of the psychiatric issues are discussed. In conclusion, the case is made for the inclusion of a specific category, in non‐dependent abuse of drugs, for caffeine.
Therapeutic drug monitoring in psychiatry—is it worthwhile?
Authors: Burgess C. D.
Published: May 2005

Although many drugs used in psychiatry can be assayed in body fluids, the measurement of agents such as the tricyclic antidepressants (TCAs) and the antipsychotic agents in the therapeutic setting remains controversial. This is due to both pharmacokinetic and pharmacodynamic factors. Pharmacokinetically, neither the TCAs nor the antipsychotics meet the criteria for therapeutic drug monitoring, because they undergo extensive first‐pass metabolism to active metabolites, their mechanism of action probably involves alteration in receptor responsiveness, and at least for the TCAs protein binding is not constant. The pharmacodynamic end points in assessing depression and schizophrenia have also proved difficult to define; thus the relationship between plasma levels and clinical response has proved elusive. Lithium, alone, is suitable for therapeutic drug monitoring because it has a narrow therapeutic range, is not protein bound, is not metabolized, and there is serum level variability for the same dose. Besides this agent, plasma level measurement is unlikely to add any benefit to the patient in the clinical setting.
Plasma fluphenazine concentrations in outpatients receiving fluphenazine decanoate (Modecate)
Authors: Kimber Nigel M. , Marriott Peter F. , Norman Trevor R. , Burrows Graham D.
Published: May 2005

Plasma fluphenazine concentrations were measured by neuroleptic radioreceptor assay in 17 outpatients receiving chronic treatment with intramuscular fluphenazine decanoate. The range of concentrations was 0.5–2.4 μg/L over the dosage range of 0.30–3.2 mg/d. Age, sex and smoking status had no influence on plasma fluphenazine concentrations, which were not correlated with dose (expressed as mg/kg/d). There was no significant correlation between plasma concentration and clinical status of the patients. No difference in plasma concentration between patients with extrapyramidal signs or tardive dyskinesia and those without signs were observed.
Transdermal scopolamine: Effects of single and repeated patches upon aspects of vision
Authors: Parrott A. C.
Published: May 2005

Transdermal scopolamine and transdermal placebo patches were administered on alternating days to 12 normal volunteer subjects. Visual near‐point values and self‐reports of blurred vision were systematically assessed 24 hours following each transdermal patch. Blurred vision was not reported following the first scopolamine patch, but became increasingly frequent following successive scopolamine patches. Six of the 12 subjects reported blurred vision by their fourth scopolamine patch. Subjects reporting blurred vision had long initial visual near‐points (i.e. were comparatively hypermetropic), whereas subjects not reporting blurred vision had short initial visual near‐points (i.e. were comparatively myopic). The visual near‐point values of the (hypermetropic) subjects who developed blurred vision became longer following each successive scopolamine patch, whereas the visual near‐point values of the (myopic) subjects not reporting blurred vision remained basically unchanged. Visual changes following scopolamine have been previously shown to be slow to develop and slow to dissipate; this slow time course probably produced the cumulative visual problems reported here.
The use of flumazenil in prevention of Diazepam dependence in the rat
Authors: Baldwin Helen A. , Hitchcott Paul K. , File Sandra E.
Published: May 2005

Rats were treated with diazepam (4 mg/kg per day) or its vehicle for 21 days. Twenty‐four hours after their last dose they were tested in the social interaction test of anxiety. Diazepam withdrawal significantly reduced the time spent in social interaction compared with controls, indicating an anxiogenic withdrawal response. The administration of a single dose of flumazenil (4 mg/kg) during chronic diazepam treatment, 7 or 14 days before testing, prevented the development of this withdrawal response. The clinical implications of these findings are discussed.
Clinical evaluation of alprazolam in patients with panic disorder: A double‐blind comparison with imipramine
Authors: Lepola U. , Heikkinen H. , Rimón R. , Riekkinen P.
Published: May 2005

The antipanic effect and tolerability of alprazolam and imipramine were compared during 9 weeks in 55 inpatients with panic disorder with or without agoraphobia. Both drugs decreased significantly the frequency of panic attacks, alprazolam as early as 3 weeks of treatment. The symptoms of generalized anxiety and depression decreased similarly in both groups. The tolerability of alprazolam appeared slightly better than that of imipramine. Drug‐induced anticholinergic side‐effects were more frequent in the imipramine group, whereas sedation, impotency, and myoclonic jerks appeared more often in the alprazolam group.
The effects of caffeine on two computerized tests of attention and vigilance
Authors: Frewer L. J. , Lader M.
Published: May 2005

Single doses of caffeine (250 mg, 500 mg) or placebo were administered double‐blind to healthy volunteer subjects (n = 12), using a fully balanced crossover design (Williams square) with 1‐week washout. Assessments were made predrug, and at 45 min and 165 min post‐drug administration. The test battery comprised physiological measures (blood pressure, heart rate and urinary volume), subjective measures of alertness, a letter cancellation task (one‐target, two‐target and four‐target versions), and two computerized measures of attention and vigilance: a rapid information processing task and a continuous attention task. Physiological variables did not alter following caffeine administration, but subjective and cognitive variables showed significant changes in the predicted direction. Thus, doserelated changes in subjective calmness and interest were observed, together with changes in performance for the letter cancellation task at low and intermediate difficulty levels. A dose‐related performance improvement was observed for the rapid information processing task. The continuous attention task was also sensitive to the effects observed for the rapid information processing task. The continuous attention task was also sensitive to the effects of caffeine. The 250 mg dose offset the decline in attention observed under placebo, and indeed facilitated performance at both post‐drug administration times. The 500 mg dose impaired performance at 45 min and improved it at the 165 min post‐administration time. Sensitivity to vigilance change was also observed within test sessions for this test, indicating that the continuous attention task was more sensitive to caffeine‐induced changes in attention than the rapid information processing task.
Effects of tetrabamate and of diazepam on sleep polygraphy during subacute withdrawal in alcohol‐dependent patients
Authors: Aubin Henri‐Jean , Goldenberg Françoise , Benoit Odile , Gillet Claudine , Roullet‐Volmi Marie‐Catherine , Barrucand Dominique
Published: May 2005

We have studied the effects of two anxiolytic drugs frequently prescribed in alcohol withdrawal, diazepam and tetrabamate, on sleep polygraphy of alcohol‐dependent patients hospitalized for alcohol detoxification. Twenty‐three inpatients (16 M and 7F) fulfilling the DSM 3R alcohol‐dependence criteria were included. Twelve patients were treated with tetrabamate and the other 11 with diazepam. Sleep polygraphy was carried out on average 15 days after alcohol withdrawal. The sleep of tetrabamate‐treated patients differs from that of diazepam‐treated patients in having a much longer duration of stage 4, at the expense mainly of stage 2. The two groups of patients had a greater total sleep time and duration of delta sleep than comparable untreated patients. These results suggest that the delta sleep deficit of abstinent alcoholics is paradoxically corrected by anxiolytic treatment. Tetrabamate seems to induce the production of delta waves during the sleep of abstinent alcoholics.
Moclobemide and specific serotonin re‐uptake inhibitor combination treatment of resistant anxiety and depressive disorders
Authors: Bakish D. , Hooper C. L. , West D. L. , Miller C. , Blanchard A. , Bashir F.
Published: May 2005

This retrospective study was undertaken with the objective of determining how effective and safe moclobemide, a specific and reversible inhibitor of monoamine oxidase‐A (RIMA), is when used in combination with specific serotonin re‐uptake inhibitors (SSRIs), in a clinical setting. A thorough chart review was done of all patients with affective and anxiety disorders seen at our centre who received combination treatment with moclobemide and an SSRI. Combination moclobemide‐SSRI treatment demonstrated good efficacy in treating treatment‐resistant patients. The combination treatment was well tolerated with very few drug interactions. Dosages should be started low, titrated slowly and carefully, and patients should be monitored closely.
The effect of mianserin hydrochloride on delirium
Authors: Nakamura Jun , Uchimura Naohisa , Yamada Shigeto , Nakazawa Yoichi , Hashizume Yuji , Nagamori Ken , Sakurai Seishi , Fukuyama Hiroo
Published: May 2005

Mianserin HCl (10–60 mg/day) was administered orally before bedtime to 46 patients (mean age: 63 years) with delirium at Kurume University Hospital. The therapeutic effects of mianserin were assessed pre‐ and post‐treatment using the Delirium Rating Scale (DRS: Trzepacz et al., 1988). The mean pre‐treatment DRS score was 21. This score decreased significantly (p<0·05) to 14 on treatment day 1 and 10 on day 3. Mianserin was observed to be effective in 85 per cent of the cases (marked improvement in 67 per cent of the patients and slight improvement in 17 per cent). of the 46 patients, 28 were classified with delirium due to direct causes such as a brain tumour or cerebrovascular disease, and 18 due to facilitating factors such as hospitalization or physical restraint. In the former group, marked improvement was observed in 54 per cent of the patients, and slight improvement in 21 per cent. The latter group demonstrated marked improvement in 89 per cent of the patients, and slight improvement in 11 per cent. In control subjects receiving haloperidol, marked improvement was observed in 62 per cent of 17 delirious patients. The plasma concentration of mianserin reached a therapeutic level within 24 h of the initiation of treatment. Hence, based on these clinical results and on measurements of plasma mianserin concentrations, mianserin can be considered effective in the treatment of delirium in elderly patients due to its rapid onset and few side‐effects. Mianserin may offer an efficacy similar to that of haloperidol in the treatment of delirium while being safer.
Enhanced blockade of 45Ca2+ uptake into platelets in manic patients with bipolar affective disorder with flunarazine and verapamil
Authors: Berk Michael , Kirchmann Nicola Helen
Published: May 2005

This study examined bipolar patients in the manic and depressed phases of bipolar disorder and controls, measuring basal radiolabelled 45Ca2+ uptake into platelets, and the effects of verapamil and fluanarazine on uptake. Radiolabelled 45Ca2+ uptake into platelets was measured in the manic (N = 13) and depressed (N = 15) phases of bipolar disorder compared to controls (N = 13) using a β liquid scintillation counter. Both flunarazine (p = 0·0196) and verapamil (p = 0·0486) caused greater inhibition of 45Ca2+ uptake in manics than controls. Flunarazine (p = 0·0209) was also associated with greater inhibition of calcium uptake in manics than depressives. Flunarazine and verapamil enhance the blockade of 45Ca2+ uptake into platelets in manic patients with Bipolar Affective Disorder.
Chronic fluvoxamine treatment reduces platelet MAO activity in medicated chronic schizophrenics
Authors: Silver Henry , Odnopozov Natan , Jahjah Nabil , Barash Igor
Published: May 2005

The effect of add‐on fluvoxamine on platelet MAO activity was studied in nine chronic schizophrenic patients on steady antipsychotic treatment. Platelet MAO activity decreased significantly after 5 weeks of treatment and remained depressed. Since fluvoxamine does not inhibit MAO activity in vitro, the findings, which are preliminary, raise the possibility that chronic SSRI treatment may modify MAO production.
Paroxetine increases serum trimipramine concentration. A report of two cases
Authors: Leinonen Esa , Koponen Hannu J. , Lepola Ulla
Published: May 2005

Paroxetine is a new antidepressant, a selective serotonin reuptake inhibitor (SSRI), which has marked inhibiting effect on microsomal cytochrome P450 enzymes in human liver. In this case report we describe two patients whose serum trimipramine and desmethyltrimipramine concentrations increased markedly when paroxetine was added to their drug therapy. We suggest that this was due to the inhibitory effect of paroxetine on the CYP 2D6‐mediated metabolism of trimipramine. This interaction may be of clinical importance as both patients had side‐effects, such as sedation and orthostatic hypotension, during the simultaneous administration.
Remoxipride versus thioridazine in the treatment of first episodes of schizophrenia in drug‐naive patients: A case for specific, low potency D2 antagonists
Authors: Lambert T. , Keks N. , McGrath J. , Catts S. , Hustig H. , Vaddadi K. , Burrows G. , Varghese F. , George T. , Kerr K. , Johnson G. , Burnett P. , Zorbas A. , Hill C. , Copolov D.
Published: May 2005

Remoxipride, a substituted benzamide, is a selective D2 antagonist with an atypical neuroleptic profile. Previous studies have demonstrated its antipsychotic efficacy against haloperidol and, more recently, thioridazine. of the 144 patients enrolled in the Australian remoxipride–thioridazine comparative trial, 28 presented for their first episode of schizophrenia and/or had no previous neuroleptic treatment. These patients form the subject of this paper.

The study found that in persons presenting for their first admission for schizophrenia, remoxipride showed equal antipsychotic efficacy compared to thioridazine. Treatments were comparable in terms of generating few extrapyramidal symptoms but thioridazine caused more significant general side‐effects. Patients are more likely to be compliant with remoxipride due to its tolerability.

Despite remoxipride being withdrawn from the market due to a suggested association with aplastic anaemia, this class of substituted benzamides warrants further examination as a treatment agent for first and subsequent episodic psychosis.
A new method for measuring permeability of bio‐impregnated textile grafts
Authors: Kaplan Alexander , Sauvage Lester R. , Kaplan Svetlana , Marcoe Karen F. , Mungin Dorothy , Wu Hong‐De , Walker Mark
Published: May 2005

Traditional water permeability evaluation procedures developed for measurement of gross leakage rates of textile prostheses are not adequate for testing the permeability of low‐porosity bio‐impregnated vascular prostheses. Obtaining reliable water permeability data for these low porosity grafts requires a technique that can accurately assess minor water leakage under the applied pressure. This study proposes an automated method for graft permeability assessment which measures the pressure change inside the graft sample as a function of water loss. The new unit of water permeability defines the pressure gradient at the given initial conditions. The proposed method for evaluating the water permeability of bio‐impregnated vascular prostheses provides highly reliable data, is accurate, and excludes human error.
Pore volume distribution of artificial skin by liquid extrusion analysis
Authors: Klein David M. , Tyomkin Ilya , Miller Bernard , Rebenfeld Ludwig
Published: May 2005

Liquid extrusion pore volume analysis was used to characterize the pore structure of the collagen‐based artificial skin material developed by Yannas and Burke.1 This technique is based on following the liquid loss from a saturated porous material as the pressure gradient across the material is increased. From the measured increments of volume of liquid drained at successively increasing pressures, each of which corresponds to a given pore radius, one obtains a cumulative pore volume curve as a function of pore radius from which pore volume distributions can be calculated. Using a nonswelling liquid (hexadecane) and a swelling liquid (aqueous surfactant solution), the effects of crosslinking and the method of drying were examined. In hexadecane, the median pore size of the uncrosslinked material is 25 μm, while for the crosslinked material, it is 115 μm. In water, the free volume of the crosslinked material is 36 mm3/mg, while for the uncrosslinked material it is an order of magnitude less. Sublimative drying provides a material with a total free volume of 55 mm3/mg, while evaporative drying collapses the porous structure to give a material with a total free volume of 8 mm3/mg. The liquid extrusion technique is relatively simple and allows pores to be measured in swollen materials in terms of their accessibility to skin cells. This method of pore characterization is considered more relevant for artificial skin than is a purely geometric characterization of pore dimensions.
Biodegradable screw fixation of rabbit tibia proximal osteotomies
Authors: Matsusue Yoshitaka , Yamamuro Takao , Yoshii Satoru , Oka Masanori , Ikada Yoshito , Hyon Suong‐Hyu , Shikinami Yasuo
Published: May 2005

The purpose of this study was to evaluate a biodegradable poly(L‐lactide) (PLLA) screw for osteosynthesis under a load‐bearing condition. A proximal tibial osteotomy on 25 rabbits was fixed with a biodegradable screw made of PLLA. A follow‐up study was done at 1, 2, 4, 8, and 16 weeks. In another 25 rabbits, the tibial osteotomy was fixed with stainless steel (SUS) screws of the same size as the PLLA screws with a similar follow‐up period. Radiographic, histological, microradiographic, and oxytetracycline‐labeling studies showed healing of the osteotomy within 4 to 8 weeks. The displacement of frag‐ments and the mass of newly formed bone around the screws were measured by histomorphometric analysis. There was no significant difference in the displacement of the fragments in these two groups and new bone was more abundantly detected in the PLLA group than in the SUS group. Histologically, no inflammatory lesion was detected in either group. All osteotomies united without delay and the displacement was minimal, although no external support was applied and the rabbits were allowed to move freely after the operation. The results of this study suggest a possible use for a PLLA screw in the clinical treatment of human bone fractures.
Mechanical test methodology for environmental exposure testing of biodegradable polymers
Authors: Smutz W. P. , Daniels A. U. , Andriano K. P. , France E. P. , Heller J.
Published: May 2005

A test methodology was developed for exposing degradable polymer test specimens to a simulated chemical and mechanical body environment and then testing them periodically to detect changes in stress–strain behavior. Poly(ortho ester) specimens were exposed to cyclic loading in aerated tris‐buffered saline (pH = 7.4) at 37°C. Specimens were removed at various time periods and the mechanical properties determined. To determine the effects of cyclic loading alone, additional specimens were cycled in air for the same cyclic periods and tested in the same manner. To determine the effects of a constant load on degradation rate, other specimens were subjected to a static load while exposed to trisbuffered saline. Additional specimens were subjected to immersion in tris‐buffered saline without loading.

Exposure to tris‐buffered saline alone had a small effect on the rate of change of the mechanical properties of the poly(ortho ester) specimens while cyclic loading in air alone had no effect. However a combination of both exposure to tris‐buffered saline and a static load decreased the flexural yield strength by 29% and the modulus of elasticity by 20% after 40 days, and a combination of both exposure to tris‐buffered saline and cyclic loading decreased both the flexural strength and modulus by 75% after 40 days.
Effectiveness of silane treatment on absorbable microfibers
Authors: Andriano Kirk P. , Daniels A. U. , Heller Jorge
Published: May 2005

Preliminary experiments suggest pretreatment of absorbable crystalline, calcium‐sodium‐metaphosphate (CSM) microfibers with trimethoxy‐based silane coupling agents yields a polysiloxane film barrier which protects the fiber surface from early dissolution due to water. Compared to thermoplastic poly(L‐lactic acid) (PLLA) composites reinforced with untreated fibers, PLLA composites reinforced with a variety of silane pretreated microfibers showed increased mechanical properties, suggesting improved adhesion was achieved at the fiber/matrix interface. Unfortunately, the silane pretreated CSM/PLLA composite showed no increase in wet strength retention after short‐term in vitro exposure. This may be due to plasticization from water entering the composite at areas of incomplete fiber wetting by the highly viscous molten PLLA. However, when a nonabsorbable, low viscosity unsaturated polyester thermoset resin was reinforced with methacryloxy‐silane pretreated CSM microfibers, there was no decrease in flexural strength and less than a 10% decrease in flexural modulus after 7 days exposure to 7.4 pH Tris‐buffered saline at 37°C.
Biocompatibility and mechanical properties of a totally absorbable composite material for orthopaedic fixation devices
Authors: Andriano Kirk P. , Daniels A. U. , Heller Jorge
Published: May 2005

Bioabsorbable polymer/inorganic phosphate fiber composites are prone to rapid degradation due to water sensitivity of the interface between the degradable polymer and the degradable fiber. This article describes successful fabrication and laboratory evaluation of a candidate bioabsorbable composite implant material with mechanical properties similar to bone. The composite studied was poly(ortho ester) reinforced with randomly‐oriented, crystalline microfibers of calcium‐sodium‐metaphosphate. The component materials showed no acute cytotoxicity as determined by tissue culture agar overlay. Treating the microfibers with a diamine‐silane coupling agent improved mechanical properties and slowed degradation in saline, but strength still decreased 50% in 1 week. When the composite material was then coated with a layer of matrix polymer alone it retained 70% of its strength and 70% of its stiffness after 4 weeks exposure to 7.4 pH Tris‐buffered saline at body temperature. The marked improvement with the coating can be attributed to the hydrophobicity of poly(ortho esters).
Fabrication and characterization of an asymmetric polyurethane membrane for use as a wound dressing
Authors: Hinrichs W. L. J. , Lommen E. J. C. M. P. , Wildevuur Ch. R. H. , Feijen J.
Published: May 2005

To prevent wound dehydration and bacterial penetration, a wound dressing should be occlusive, but on the other hand it should also be permeable for wound exudate to prevent bullae formation. To meet these requirements a new type of polyurethane wound dressing which consists of a microporous top layer (pore size < 0.7 μm) supported by a sublayer with a highly porous sponge‐like structure containing micropores (pore size <10 μm) as well as macropores (pore size: 50–100 μm) was designed. The pores of both layers are interconnected and form a continuous structure in the membrane. Membranes according to this design were prepared either by means of a two‐step or by means of a one‐step casting process. Both fabrication methods are based on phase inversion techniques. Asymmetric polyurethane Biomer® membranes prepared by the two‐step casting process were tested in vivo as full thickness skin substitutes using guinea pigs. Neither wound dehydration nor infections were observed while the drainage capacity of the wound dressing was effective in preventing bullae formation. Furthermore the wound dressing remained firmly adhered to the wound surface during the whole process of wound healing. In contrast to all other commercial wound dressings currently available the polyurethane wound dressing applied on excised clean wounds did not need to be replaced during healing but could be left on the wound until full regeneration of the skin had taken place after which it was spontaneously repelled. © 1992 John Wiley & Sons, Inc.
A study of the bioactive bone cement–bone interface: Quantitative and histological evaluation
Authors: Nishimura Naomi , Taguchi Yasushi , Yamamuro Takao , Nakamura Takashi , Kokubo Tadashi , Yoshihara Satoru
Published: May 2005

The interface between bone and a bioactive glass cement—a mixture of bioactive glass powder and ammonium phosphate solution, previously reported on by the authors—was evaluated quantitatively and histologically. The materials tested were (1) the original bioactive glass cement (BCI cement); (2) an improved type of bioactive glass cement (BCII cement); (3) polymethylmethacrylate (PMMA) bone cement; and (4) a bioactive, apatite–wollastonite‐containing, glass ceramic (A‐W·GC). Hardened cylindrical specimens of each cement were inserted loosely into canine femora and the interfacial shear strengths were measured using a push‐out test. The interfacial strength values of the bioactive glass cements increased with prolonged implantation time. At each postimplantation time studied (8, 12, and 24 weeks), the interfacial strength value of BCI cement did not differ significantly from that of A‐W·GC. BCII cement interfacial strength was greater than that of BCI cement, whereas the interfacial strength of PMMA bone cement remained at a very low level throughout the study. Histological examinations revealed that direct bonding of both bioactive glass cements to bone had occurred without pathologic degradation. After 24 weeks, the defects between the bone and the bioactive glass cements had been filled with mature lamellar bone. Because the bioactive glass cement system developed by the authors, especially BCII cement, shows excellent osteoconductivity and bonds to bone tightly, we consider it to be a promising material for fixing prostheses into bone. © 1993 John Wiley & Sons, Inc.
Effect of thermal treatment on heating characteristics of NiCu alloy for hyperthermia: Preliminary studies
Authors: Ferguson S. D. , Paulus J. A. , Tucker R. D. , Loening S. A. , Park J. B.
Published: May 2005

Ferromagnetic NiCu alloy wires were characterized in order to obtain well‐defined thermoseeds for application in interstitial hyperthermia of prostate cancer. Thermoseeds have been produced which possess Curie points in the therapeutic hyperthermia range, approximately 40 to 50 °C. The effect of thermal treatment and composition on the heating characteristics of the thermoseeds were investigated. The preliminary study shows that the recrystallization is crucial for altering thermoseeds' heating characteristics. Obtaining thermoseeds which behave as desired depends on changes in annealing times and temperatures. One may increase the maximum heating temperature (similar to Curie temperature) by increasing the annealing time and cooling time. Decreasing the lower annealing plateau temperature also increases the maximum seed heating temperature. Higher nickel content compositions did not affect rise time but increased the maximum heating temperature. © 1993 John Wiley & Sons, Inc.
Handling characteristics of braided suture materials for tight tying
Authors: Tomita Naohide , Tamai Susumu , Morihara Tsutomu , Ikeuchi Ken , Ikada Yoshito
Published: May 2005

The establish criteria for characterizing synthetic sutures, the handling characteristics of silk suture were analyzed. The characteristics that distinguish silk suture from other braided suture materials are its good “knot security” and relatively low “tiedown resistance.” Analytic consideration of knot security suggests that not only superficial friction but also resistance force produced by cross‐sectional deformity of braided threads plays an important role in silk's superior performance. Results of a “pullout friction test,” developed to quantitatively evaluate resistance produced by surface friction and cross‐sectional deformity suggest that the superiority of silk thread can be explained in terms of high static withdrawal resistance under low loads and relatively low dynamic withdrawal resistance under high loads. © 1993 John Wiley & Sons, Inc.
Diffusion of fibroblast growth factor from a plaster of paris carrier
Authors: Rosenblum S. F. , Frenkel S. , Ricci J. R. , Alexander H.
Published: May 2005

Fibroblast growth factor (FGF) is a polypeptide that has been shown to have a stimulatory effect on osseous tissues in vitro. This study characterized the release of FGF from plaster of Paris (PLP) and measured the dissolution of PLP in various solutions with the aim of developing a reliable carrier system for the release of FGF in vivo. The study consisted of five experiments: (I) FGF diffusion from PLP pellets, (II) FGF diffusion from PLP discs, (III) PLP dissolution in saline, (IV) PLP dissolution in serum, and (V) FGF adsorption by commercially pure titanium. FGF was observed to be released at a rate directly proportional to the rate of dissolution of the PLP carrier, suggesting that either the FGF binds to the PLP; or, alternatively, the FGF may be entrapped by the PLP. Dissolution rate, and thus release rate, could be varied by varying the mass of the carrier. Greater diffusion of FGF was observed in larger, more slowly dissolving PLP carriers. Dissolution of PLP was observed to be slower in serum than in saline, apparently due to stabilization by factors in the serum but not due to a concentration gradient effect. Titanium coupons did not adsorb significant amounts of FGF. These results indicate that PLP, which has been shown in the past neither to FGF. These results indicate that PLP, which has been shown in the past neither to aggravate inflammatory response nor to interfere with bone ingrowth, may serve as delivery vehicle for FGF to osseous tissues in vivo. © 1993 John Wiley & Sons, Inc.
On the use of primary reference grade polydimethylsiloxane
Authors: Schmidt John A. , von Recum Andreas F.
Published: May 2005

There has been an increase in the use of primary reference material as a standard for identifying the cellular response to biomaterials. One such material is NHLBI–DTB polydimethylsiloxane (PDMS). The PDMS was developed for blood contacting studies and is composed of PDMS backed on one side with mylar. The results of implantation studies of two different publications are discussed in light of the different materials and different surface topographies of each of the materials. The appropriateness of in vivo studies using this reference material is questioned. © 1993 John Wiley & Sons, Inc.
A study of the geometrical and mechanical properties of a self‐expanding metallic stent—theory and experiment
Authors: Jedwab Michael R. , Clerc Claude O.
Published: May 2005

Stents are tubular devices that are used in cylindrical passages of the body following trauma or disease in order to keep the cross section of these passages open. A mathematical model of a self‐expanding metallic stent has been developed with the aim of predicting various geometrical and mechanical properties of the stent. The model was developed with the main assumptions that the stent acts as a combination of a number of independent open‐coiled helical springs with ends fixed against rotation, and that the springs undergo elastic deformations only. A series of experiments has been carried out in order to assess the validity of the model. The experimental results show good agreement with theory for the tests involving stent diameter and longitudinal force as a function of stent length and fair agreement, limited by frictional effects, for the tests involving radial pressure as a function of stent diameter. © 1993 John Wiley & Sons, Inc.
Biomechanical performance of new vascular sutures and needles for use in polytetrafluoroethylene grafts
Authors: Towler Michael A. , Tribble Curtis G. , Pavlovich Lucas J. , Milam James T. , Morgan Raymond F. , Edlich Richard F.
Published: May 2005

Two new cardiovascular monofilament sutures attached to taper point needles have been developed for use in expanded polytetrafluoroethylene (PTFE) grafts. One monofilament suture made of PTFE has a microporous structure that allows it to be channel swaged to a needle that closely approximates its suture diameter. The other suture is a monofilament polypropylene suture that has been extruded to produce a tapered swage end, which was significantly smaller than that of the remainder of the suture in order to be channel swaged to smaller diameter needles. On the basis of comprehensive biomechanical performances, the performance of the new needle suture products with needle/suture diameter ratios approaching 1:1 was superior to needle suture products with 2:1 needle/suture diameter ratios for use in PTFE vascular grafts, regardless of the suture material. © 1993 John Wiley & Sons, Inc.
A new bioactive bone cement consisting of BIS‐GMA resin and bioactive glass powder
Authors: Kawanabe Keiichi , Tamura Jiro , Yamamuro Takao , Nakamura Takashi , Kokubo Tadashi , Yoshihara Satoru
Published: May 2005

We have developed a bioactive bone cement consisting of silane‐treated CaOSiO2P2O5CaF2 glass powder as the filling particles and bisphenol‐a‐glycidyl methacrylate (BIS‐GMA) diluted with triethylene‐glycol dimethacrylate (TEGDMA) as the organic matrix. Histological examination demonstrated direct bonding between the cement and bone along the circumference of the cement at 4 weeks after implantation in rat tibia. The compressive strength and toughness of the cement were two and four times greater than those of polymethylmethacrylate (PMMA) cement, respectively. The inflammatory reaction of the skin caused by the new cement was not as intense as that for PMMA 3 days after subcutaneous implantation. This new cement may be applicable as a bioactive bone cement with high mechanical strength. © 1993 John Wiley & Sons, Inc.