bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Fluoxetine and Dothiepin on 24-Hour Activity in Depressed Patients
Authors: Stanley Neil , Fairweather Diane B. , Hindmarch Ian 
Published: April 2003

Psychomotor retardation is a recognised symptom of depressive illness, and improvement in psychomotor function is associated with the amelioration of the severity of depressive symptoms. Actigraphy permits behavioural activity to be continuously assessed, allowing changes in psychomotor activity to be monitored over time. A randomised, parallel-group, double-blind study was conducted in 14 general practice patients with a diagnosis of major depression. This pilot study was designed to investigate the utility of actigraphy in this patient population and to investigate possible differences between fluoxetine and dothiepin in their effects on 24-hour behavioural activity monitored for the first 10 days of treatment. Patients taking dothiepin (75 mg rising to 150 mg in the second week, nocte) were found to be significantly (p < 0.05) less active over the course of the day compared to those treated with fluoxetine (20 mg, mane). This lower level of behavioural activity in the dothiepin group was particularly noticeable in the early morning (06:00–08:00 h).
The Effects of Scopolamine on Changes in Regional Cerebral Blood Flow during Classical Conditioning of the Human Eyeblink Response
Authors: Bahro Marcel , Molchan Susan E. , Sunderland Trey , Herscovitch Peter , Schreurs Bernard G. 
Published: April 2003

We examined the effects of scopolamine on the functional anatomy of classical conditioning of the human eyeblink response. Ten healthy young normal female volunteers (mean age ± SEM: 26.7 ± 0.9 years) were administered 0.4 mg scopolamine intravenously 1 h before regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and H<sub>2</sub><sup>15</sup>O. Scans occurred during three sequential phases: (1) explicitly unpaired presentations of the unconditioned stimulus (airpuff to the right eye) and conditioned stimulus (binaural tone), (2) paired presentations of the two stimuli (associative learning) and (3) explicitly unpaired presentation of the stimuli (extinction phase). Scopolamine impaired acquisition of the conditioned eyeblink response (54.7 ± 4.9%) relative to 18 untreated subjects from two previous PET studies. Regions that showed significant relative increases in rCBF during conditioning included the right lateral occipital cortex, the right inferior occipital cortex, the right lateral temporo-occipital cortex, the left medial temporo-occipital cortex, the posterior cingulate, the right cerebellum/brain stem area and the medial cerebellum. Significant relative decreases in rCBF were measured in the thalamus, the left putamen/insula area, the right putamen and the left and middle cerebellar cortex. The data partially replicate previous findings in unmedicated young volunteers of conditioning-specific rCBF changes in the cingulate cortex, the cerebellar cortex, the insula and the lateral temporo-occipital cortex. Our finding of decreased rCBF in the thalamus and increased rCBF in the occipital cortex may be attributable to effects of scopolamine per se rather than conditioning. Our data lend further support to the notion that classical conditioning involves distributed changes in multiple systems within the central nervous system.
Effects of Paroxetine on Heart Period Variability in Patients with Panic Disorder: A Study of Holter ECG Records
Authors: Yeragani Vikram K. , Jampala V.C. , Sobelewski Edward , Kay Jerald , Igel Gina 
Published: April 2003

We investigated cardiac autonomic function in 16 patients with panic disorder before and after treatment with paroxetine using Holter ECG records. Our previous data suggest a relative increase in sympathetic activity in patients with panic disorder, especially during sleep. Data for 20 h and awake and sleep periods were analyzed using spectral analysis to quantify absolute and relative heart period variability in ultra low (ULF: <0.0033 Hz), very low (VLF: 0.0033–0.04 Hz), low (LF: 0.04–0.15 Hz) and high (HF: 0.15–0.5 Hz) frequency bands. We also obtained fractal dimensions (FD) for the 20-hour, awake and sleep time series of RR intervals. Paroxetine treatment (19.7 ± 4.7 mg/day for 105 ± 37 days) resulted in a significant improvement in the frequency and intensity of panic attacks and also on the state anxiety inventory. Paroxetine treatment produced a significant decrease of 20-hour absolute HF power, awake absolute LF power and sleep absolute HF power. There was also a significant decrease of FDs after treatment with paroxetine for the sleep period. The decrease in LF and HF powers, and sleep FD is likely due to the antimuscarinic effect of paroxetine. The decrease in day-time LF power may also be due to a decrease in relative cardiac sympathetic activity after paroxetine treatment.
Effects of Serotonin-Selective and Classical Antidepressants on the Auditory P300 Cognitive Potential
Authors: d’Ardhuy X. Liogier , Boeijinga P.H. , Renault B. , Luthringer R. , Rinaudo G. , Soufflet L. , Toussaint M. , Macher J.-P. 
Published: April 2003

The cognitive potential, P300, is a phenomenon frequently studied in relation to template matching of the brain. To understand the neurochemical mechanisms of its generation, we compared the effects of three antidepressants, fluoxetine, tianeptine and clomipramine after single and repeated application as well as after 1 week of withdrawal on the P300 and N200 waves in an auditory ‘odd-ball’ paradigm in three parallel groups of 10 healthy volunteers. Following single administration, both fluoxetine and clomipramine reduced (–39 ± 14%, p < 0.01) the peak amplitude of P300 at the Pz electrode. For fluoxetine and tianeptine, reduced amplitudes of 19 ± 7% and 24 ± 11%, respectively, were found following 8 days of treatment, 2 h after administration. However, for clomipramine no additional diminution was found on day 8 with respect to day 1. Topographic distributions tended to be significantly modified at the frontal scalp area 1 h after the tianeptine administration on day 8, whereas the postdosing changes induced by fluoxetine were localised in the midline and right centrotemporal scalp regions. Only minor reductions in peak latencies have been observed. It can be concluded that serotonin selective drugs have a slower onset of P300 amplitude decrease than clomipramine, which has additional effects on monoaminergic and on cholinergic systems. These results suggest that serotonin has a regulatory function in the neurotransmission of cerebral structures which are involved in the evaluation of stimulus relevance.
Endocrine Responses after <i>d</i>-Fenfluramineand Ipsapirone Challenge: Further Support for Cloninger’s Tridimensional Model of Personality
Authors: Hennig J. , Toll C. , Schonlau P. , Rohrmann S. , Netter P. 
Published: April 2003

The tridemensional model of personality introduced by Cloninger relates aspects of novelty seeking to the dopaminergic, harm avoidance (HA) to the serotonergic, and reward dependence to the noradrenergic neurotransmitter system. Using a neuroendocrine challenge paradigm, this study investigates whether subjects characterized by blunted cortisol (CORT) responses after ipsapirone (IPS) relate to different subfactors of HA from those characterized by blunted prolactin (PRL) responses after treatment with <i>d</i>-fenfluramine (D-FEN). Moreover, subjects blunted in both responses should differ in scale values of subfactors of HA from those with only one or no blunted reactions. In the first part of the experiment, 16 healthy male volunteers were treated with 15 mg D-FEN. The second part of the study (about 1 year later) consists of a challenge with the partial 5-hydroxytryptamine-1a (5-HT<sub>1a</sub>) agonist IPS (10 mg) in the same subjects. The results indicate that blunted PRL responses are accompanied by high values in HA, while the main effect of IPS responsivity did not relate significantly to this dimension. With respect to the subscales of HA, subjects blunted in both responses (PRL–/C–) exhibit significantly higher levels in fatigability and asthenia when compared to all other groups (PRL–/C+, PRL+/C–,PRL+/C+). The data demonstrate that combined challenge tests may shed more light on the biological basis of personality and that HA and most clearly fatigability and asthenia relate to the 5-HT system.
Sleep Laboratory Studies in Restless Legs Syndrome Patients as Compared with Normals and Acute Effects of Ropinirole
Authors: Saletu B. , Gruber G. , Saletu M. , Brandstätter N. , Hauer C. , Prause W. , Ritter K. , Saletu-Zyhlarz G. 
Published: April 2003

Although the restless legs syndrome (RLS) is a disorder with a relatively high prevalence rate (8% in Austria) and leads to insomnia and excessive daytime tiredness, there is a paucity of sleep laboratory data concerning objective and subjective sleep and awakening quality. Thus, the aim of this study was to investigate 12 untreated RLS patients as compared with 12 normal controls and subsequently measure the acute effects of 0.5 mg ropinirole (Requip<sup>®</sup>) – a nonergoline dopamine agonist – as compared with placebo. In 3 nights (adaptation, placebo, ropinirole night) sleep induction, maintenance and architecture were measured objectively by polysomnography, subjective sleep and awakening quality were assessed by self-rating scales and visual-analog scales, and objective awakening quality was evaluated by a psychometric test battery. In polysomnography, RLS patients demonstrated, as compared with normal controls, a decreased total sleep time (TST) and sleep efficacy, increased wakefulness during the total sleep period and frequency of nocturnal awakenings, increased sleep stage S1, decreased S2 and increased stage shifts. Subjective sleep quality tended to decrease, and morning well-being, mood, affectivity and wakefulness were deteriorated. In the noopsyche, fine motor activity and reaction time performance were deteriorated. Ropinirole 0.5 mg induced, as compared with placebo, an increase in TST, sleep efficacy, S2 sleep and stage shifts. In the morning, somatic complaints increased slightly, while fine motor activity and reaction time performance improved. Our findings suggest a key-lock principle in the diagnosis/treatment of RLS and a dopaminergic mechanism in its pathogenesis, which is supported by the data on periodic leg movements during sleep and arousals of the subsequent paper.
Effect of Conjunctival Structure and Inflammatory Cell Counts on Intraocular Pressure after Trabeculectomy
Authors: Arıcı Mustafa Kemal , Demircan Süleyman , Topalkara Ayşen , Güler Cenap , Aker Handan , Arıcı Dilek Sema 
Published: April 2003

<i>Purpose:</i> To evaluate the conjunctival structure and inflammatory cell counts and to determine the predictive value of these histological parameters for postoperative intraocular pressure (IOP) levels after trabeculectomy. <i>Methods:</i> A clinical and histological study was performed on consecutive patients. Postoperative (mean 32.8 ± 18.4 months; range 6–60 months) conjunctival biopsies of 36 eyes of 28 primary open-angle glaucoma patients who had trabeculectomy between 1992 and 1995 were included in the study. According to postoperative pressure control, patients with ≤16 mm Hg and those with >16 mm Hg were taken as groups 1 and 2, respectively. The control group (group 3) consisted of 15 age-matched patients without glaucoma, who had received no topical therapy. We compared the conjunctival structure and cell counts within these groups. Goblet cells, acute inflammatory cells, chronic inflammatory cells, fibroblasts, epithelial thickness, vascular density, mucopolysaccharides and collagen compositions were determined in groups 1, 2 and 3. <i>Results:</i> The number of goblet cells was significantly higher in group 1 (6.74 ± 7.23) than group 2 (3.09 ± 2.77; p = 0.017). No statistical difference was observed in the number of acute inflammatory cells, chronic inflammatory cells, fibroblasts, epithelial thickness, vascular density, mucopolysaccharide or collagen compositions between groups 1 and 2 (p > 0.05). In addition, when groups 1 and 2 were compared with the control group, there was a significant decrease in goblet cells (p < 0.001), an increase in acute inflammatory cells, chronic inflammatory cells, fibroblasts, epithelial thickness and vascular density (p < 0.001), but there was no significant difference in mucopolysaccharide and collagen compositions (p > 0.05). <i>Conclusions:</i> This study suggests that at the time of surgery a high number of goblet cells may be a predictor of lowered IOP (≤16 mm Hg) following trabeculectomy without antimetabolite.
Ist die Positronen-Emissions-Tomographie (PET) zum Nachweis tumorbefallener Halslymphknoten bei Plattenepithelkarzinomen des Kopf-Halsbereiches in der klinischen Routine sinnvoll einsetzbar?
Authors: Kau R.J. , Alexiou C. , Werner M. , Schwaiger M. , Arnold W. 
Published: April 2003

<i>Zielsetzung:</i> Bei Patienten mit Plattenepithelkarzinomen der Kopf-Halsregion ist zur Festlegung einer individualisierten Therapie die genaue Bestimmung der Halslymphknotenbeteiligung unabdingbar. In einer vorangegangenen Untersuchung konnten wir zeigen, dass <sup>18</sup>F-FDG-PET mit und ohne Schwächungskorrektur in einem wissenschaftlichen Untersuchungsprotokoll der Kernspintomographie überlegen ist. In der vorliegenden Arbeit sollte die diagnostische Genauigkeit eines verkürzten PET-Protokolls (Aufnahmezeit 20 min) untersucht werden. <i>Studiendesign:</i> Statische, nicht-schwächungskorrigierte PET-Aufnahmen, wurden in 2 Bettpositionen 40 min. im Anschluss an die intravenöse Gabe von 370 MBq <sup>18</sup>F-FDG gewonnen und mit den morphologischen bildgebenden Verfahren (CT u. MRT) verglichen. 70 nicht vorselektierte Patienten wurden so zur Festlegung des Lymphknotenstatus untersucht. Die postoperativen pathologischen Ergebnisse dienten als «gold standard». <i>Ergebnisse:</i> Die diagnostische Genauigkeit der Positronenemissionstomographie zur Beurteilung der tumorbefallenen «Halsseiten» war dem morphologischen Verfahren mit einer Sensitivität von 87% und einer Spezifität von 94% gegenüber CT 65%, bzw. 47% und MRT mit 88% bzw. 41% deutlich überlegen. <i>Schlussfolgerung:</i> Ein abgekürztes PET-Protokoll ist für die klinische Routine einsetzbar und dem morphologischen Verfahren (CT u. MRT) in der Diagnostik von malignen, infiltrierten Lymphknoten des Kopf-Hals-Bereiches, auch in der klinischen Routine, überlegen.
Enhancement of Atherosclerosis in Beta-2-Glycoprotein I-Immunized Apolipoprotein E-Deficient Mice
Authors: Afek Arnon , George Jacob , Shoenfeld Yehuda , Gilburd Boris , Levy Yair , Shaish Aviv , Keren Pnina , Janackovic Zora , Goldberg Iris , Kopolovic Juri , Harats Dror 
Published: April 2003

We have previously shown that low density lipoprotein receptor-deficient (LDL-RD) mice immunized with β<sub>2</sub>-glycoprotein I (β2GPI; a target of autoimmune anticardiolipin antibodies) developed enhanced early atherosclerosis, when fed a normal chow diet. The current study was undertaken to evaluate the effect of immunization with β2GPI and the addition of a high fat diet on the progression of atherosclerosis in the apolipoprotein E (ApoE)-deficient mouse. Six-week-old female ApoE-deficient mice (n = 10) were immunized subcutaneously with either human β2GPI or with ovalbumin, both emulsified in complete Freund’s adjuvant and fed a high fat diet for 6 weeks. The β2GPI-immunized mice were found to develop accelerated atherosclerosis when compared with their ovalbumin-immunized littermates (aortic lesion area of 137,500 ± 13,801 vs. 72,444 ± 14,465 µm<sup>2</sup>, respectively; p = 0.0067). The β2GPI-immunized mice developed high titers of anti-β2GPI antibodies, 10 days after the procedure, which were sustained until the sacrifice. LDL extracted from both study groups displayed similar susceptibility to ex vivo oxidation. These results confirm our previous study in which we found increased atherosclerosis in β2GPI-immunized LDL-RD mice fed a chow diet. In the current study we show that the proatherogenic effect of β2GPI immunization is maintained despite high cholesterol levels and is not associated with increased susceptibility of LDL to ex vivo oxidation.
Treatment of Established Tumor Is Associated with ICAM-1 Upregulation and Reversed by CD8 Depletion in a Tumor Necrosis Factor-Alpha Gene Transfected Mouse Mammary Tumor
Authors: Matory Yvedt L. , Dorfman David M. , Wu Lei , Chen Man , Goedegebuure Peter , Eberlein Timothy J. 
Published: April 2003

<i>Introduction:</i> We have performed TNF-α gene transfection in a mouse mammary cancer line and found significant antitumor effects. We hypothesize that the antitumor effects observed in this model are mediated by ICAM-1 and by the recruitment of CD4+ and CD8+ T cells. In vivo (Balb/c mice) tumor growth inhibition, treatment of established tumor and the effects of ICAM-1 and CD4+ and CD8+ T cells were evaluated. <i>Methods and Results:</i> Gene transfection with highly efficient vectors resulted in secretion of large amounts of TNF-α (ELISA). In vivo antitumor effects were tested. The number of cells required to generate palpable tumor 7–10 days after subcutaneous injection was determined (1 × 10<sup>6</sup>). The same number of transfected cells were injected subcutaneously and compared to nontransfected controls. Tumors were measured blindly and size was analyzed on day 30 by the Wilcoxon rank sum test. Mean tumor size after injection of transfected cells is compared to that of controls. Control tumors reached the maximum allowable size by day 30 (4 cm<sup>2</sup>). On day 30 EMT6-TNF-α tumors were 0.48 cm<sup>2</sup> (p < 0.05). The effect of repeat injection (challenge was also tested. Animals were injected with transfected cells or wild-type control on day –6 and challenged with the same number of wild-type tumor cells on day 0. Significant immune protection against subsequent challenge was seen after first time injection with EMT6-TNF-α but not after first time EMT6 wild-type injection (1.62 vs. 4 cm<sup>2</sup>). Treatment of 6-day-old tumor was also evaluated. On day 30, mean tumor size in animals treated with EMT6-TNF-α was 0.9 cm<sup>2</sup> compared to 4 cm<sup>2</sup> for controls. In all experiments, CD8+ T cell depletion and CD4+ T cell depletion caused a reversal of TNF-α-induced inhibitory effects. In addition, in vivo antibody blocking of ICAM-1 in tumor growth experiments reversed antitumor effects (control 4 cm<sup>2</sup>, TNF-α 0.2 cm<sup>2</sup> and ICAM-1 blocking 3.14 cm<sup>2</sup>). Using flow cytometry, MHC class I and II and ICAM-1 adhesion molecule expression of transfected tumor was tested. ICAM-I expression was significantly upregulated. MHC class II antigen expression was also increased. TNF-α-transfected human breast cancer was also evaluated. Three cell lines and fresh tumor were transfected to express TNF-α. In vitro analysis revealed ICAM-1 upregulation following transfection. Histologic analysis and immunohistochemical staining revealed TNF-α and ICAM-1 in transfected tumors and not in wild-type tumors. <i>Conclusion:</i> Highly significant in vivo tumor growth inhibition and immune protection after injection with TNF-α-transfected tumors appears to be mediated predominantly by CD8+ T cells and ICAM-1 upregulation. These findings suggest that TNF-α increases recruitment and adhesion of effector T cells.
Magnesium Fortification of Drinking Water Suppresses Atherogenesis in Male LDL-Receptor-Deficient Mice
Authors: Sherer Yaniv , Shaish Aviv , Levkovitz Hana , Keren Pnina , Janackovic Zora , Shoenfeld Yehuda , Harats Dror 
Published: April 2003

Magnesium, an important cofactor of more than 300 enzymes, has previously been found to modulate blood lipid levels, atherogenesis and atherosclerosis in rabbits, when added to their diet. The aim of this study was to examine whether magnesium fortification of drinking water, without a change in diet content, can affect atherogenesis. The study included six groups of LDL-receptor-deficient mice. The mice received either distilled water or water containing 50 g of magnesium sulfate per liter. In the first (12 weeks) and second (6 weeks) stages of the experiment, the mice received low- and high-cholesterol diets, respectively. At the end of each stage, blood was drawn for the determination of plasma magnesium, calcium and lipid levels. In addition, the extent of atherosclerosis was determined at the aortic sinus. In both males and females, magnesium fortification was associated with higher levels of plasma magnesium (50 and 37% increase, respectively), without any differences in plasma calcium content. The extent of atherosclerosis at the aortic sinus in the male mice that received high levels of magnesium was a third of that of the male mice that received distilled water. However, these differences were not found in the female groups. Surprisingly, the female mice that received water fortified with magnesium had higher levels of cholesterol after stage 2, whereas no differences regarding plasma lipid levels were found among the male mice. These results confirm that magnesium fortification of drinking water is capable of inhibiting atherogenesis in male LDL-receptor-deficient mice. The mechanisms of action are yet to be discovered, and are probably not related to diminished lipid excretion, but possibly to the prevention of calcium influx into vascular smooth muscle cells, elevated antioxidative capacity, or other yet undetermined mechanisms.
Increased Muscarinic Receptor Blockade by Atropine in Tracheal Chains of Ovalbumin-Sensitized Guinea Pigs
Authors: Boskabady M.H. , Adel-Kardan S. 
Published: April 2003

Drug delivery to the receptor sites and receptor affinity could be determinant factors for increased bronchial responsiveness seen in asthma. Competitive antagonism blockade which is measured as dose ratio – 1 (DR-1) depends only on these two factors. Therefore, in this study we examined the muscarinic receptor blockade by atropine on isolated tracheal chains of sensitized compared to control guinea pigs. An experimental model of asthma was induced in guinea pigs by sensitization of animals with injection and inhalation of ovalbumin (OA). The responses of tracheal chains of sensitized and control animals (for each group n = 10) to cumulative concentrations of methacholine in the absence and presence of 5 nmol/l atropine were measured, and the effective concentrations of methacholine causing 50% of maximum response (EC<sub>50</sub> M) were obtained. The atropine blockade (DR-1) was calculated by: (post-atropine EC<sub>50</sub> M/EC<sub>50</sub> M) – 1. The responses of tracheal chains to 0.1% OA, relative to contraction obtained by 10 mmol/l methacholine, were also measured. The tracheal responses of sensitized guinea pigs were significantly higher than those of control animals to both OA (mean ± SEM, 55.94 ± 5.22 vs. 2.59 ± 0.85%, p < 0.001) and methacholine (EC<sub>50</sub> M for asthmatic and control animals were 0.88 ± 0.27 and 2.00 ± 0.26 μmol, respectively, p < 0.01). The muscarinic receptor blockade by atropine (DR-1) was also significantly higher in tracheas of asthmatic compared to that of control animals (131.12 ± 19.82 vs. 24.50 ± 3.19, p < 0.001). There were significant correlations between tracheal response to OA and EC<sub>50</sub> M (r = –0.644, p = 0.002) and also between DR-1 and tracheal responses to both OA (r = 0.738, p < 0.001) and EC<sub>50</sub> M (r = –0.679, p < 0.001). This enhanced muscarinic receptor blockade in tracheal chains of sensitized animals confirms our previous findings which was predicted to be due to the increased drug delivery to the receptors. Drug delivery could also be a determinant factor for bronchial responsiveness to stimuli in asthma.