bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Polymer‐Modified Hanging Mercury Drop Electrode in the Indirect Determination of Certain β‐Lactam Antibiotics by Differential Pulse, Ion‐Exchange Voltammetry
Authors: Prasad Bhim Bali , Arora Bhavana
Published: September 2003

A selective and sensitive polymer‐modified electrode was developed for β‐lactam antibiotics (cefaclor, amoxycillin and ampicillin) present in formulated and blood plasma samples for the quantitative analysis in aqueous environment. The detection was made using an ion‐exchange voltammetric technique, in differential pulse mode, on poly(N‐chloranil N,N,N′,N′‐tetramethylethylene diammonium dichloride)‐modified hanging mercury drop electrode of a three‐electrode system (PAR Model 303A) attached with a Polarographic Analyzer/Stripping Voltammeter (PAR Model 264A). Antibiotics, which are electroinactive compounds, were essentially converted to their electroactive oxazolone analogues through acid treatment under drastic conditions (0.1 mol L−1 HCl, ∼85 °C, 2 h). These analytes in the form of their respective oxazolones were indirectly analyzed by oxazolone entrapment in the polymeric film through ion‐exchange process at modified electrode surface (accumulation potential −0.20 V (vs. Ag/AgCl), accumulation time 120 s, pH 7.4, KH2PO4‐NaOH buffer (ionic strength 0.1 mol L−1), scan rate 10 mV s−1, pulse amplitude 25 mV). The limit of detection of cefaclor‐derived oxazolone was found to be 2.12 nmol L−1 (0.82 ppb, S/N 3, RSD 3.21%) in terms of cefaclor (a representative β‐lactam) concentration.
Size really doesn't matter
Authors: Lawrence Bethan , Campbell Mari , Neiderman Marc , Serpell Lucy
Published: September 2003

Objective:

The judgement of what constitutes a large amount of food is one part of determining a binge and is therefore crucial for the diagnosis of BN. This study aimed to determine whether eating disorder professionals agree on what constitutes a large amount of food and the criterion they use to make the decision.

Method:

147 eating disorder professionals completed a short questionnaire, that involved rating five food vignettes according to whether they believed them to consist of a large amount of food.

Results:

There was general consensus among eating disorder professionals as to what constituted a large amount of food. The results also suggested that many participants based their judgement on how dissimilar the vignette was to a normal meal.

Discussion:

The finding that the judgement of whether an amount of food is large can be made with high reliability but low validity should be the subject of further research due to its importance in the diagnosis of bulimia nervosa. Copyright © 2003 John Wiley & Sons, Ltd and Eating Disorders Association.
Media exposure, body dissatisfaction and disordered eating: television and magazines are not the same!
Authors: Tiggemann Marika
Published: September 2003

Objective:

This study aimed to investigate the relationship between media exposure and body dissatisfaction and disordered eating in a more finely grained way than in previous studies.

Method:

A sample of 104 female undergraduate students completed measures of both magazine and television exposure, as well as measures of body dissatisfaction, disordered eating, awareness and internalization of societal ideals.

Results:

While both media exposure variables were correlated with body dissatisfaction, the pattern of correlations was very different with the other variables. In particular, the amount of magazine reading, but not television watching, was positively correlated with internalization of thin ideals. On the other hand, time spent watching television was negatively correlated with awareness of sociocultural ideals and self‐esteem.

Discussion:

It was concluded that the processes through which television and magazines impact on body dissatisfaction are different. The relationship between magazine exposure and body dissatisfaction is mediated by internalization of thin ideals, which is not the case for television exposure. Copyright © 2003 John Wiley & Sons, Ltd and Eating Disorders Association.
Eating‐disordered patients with and without self‐injurious behaviours: a comparison of psychopathological features
Authors: Claes Laurence , Vandereycken Walter , Vertommen Hans
Published: September 2003

Objective:

A considerable number of eating‐disordered patients also display all kinds of self‐injurious behaviours (SIB), which might be viewed as an indicator of psychopathological severity.

Method:

To test this hypothesis in 70 females admitted to a specialized treatment programme for eating disorders, a wide spectrum of psychopathological features was studied by means of self‐reporting questionnaires: clinical symptomatology, personality disorders, aggression regulation, trauma history, dissociation and body experience. A comparison was made between patients with (n = 27) and without SIB (n = 43), as well as between patients with one (n = 13) versus more types (n = 14) of SIB.

Results:

In general, patients with SIB reported significantly more complaints or signs of anxiety, depression, hostility, cluster B personality disorders, feelings of anger, traumatic experiences, dissociation and negative appreciation of body size. The presence of more than one type of SIB was linked to a more pronounced clinical symptomatology and trauma history. . Copyright © 2003 John Wiley & Sons, Ltd and Eating Disorders Association.
Dyadic adjustment in parents of daughters with an eating disorder
Authors: Espina Alberto , de Alda Iñigo Ochoa , Ortego Asunción
Published: September 2003

Objective:

To study the dyadic adjustment in parents of daughters with an eating disorder (ED).

Method:

147 couples, 74 with a daughter with an ED: 20 with anorexia nervosa, restricting subtype (ANR), 23 with anorexia nervosa, bulimic subtype (ANB), and 31 with bulimia nervosa purging subtype (BN), and two control groups: 41 couples without pathology (CN group) and 32 couples with pathology (CNP group), evaluated with the General Health Questionnaire (GHQ‐28), were assessed with the Dyadic Adjustment Scale, the Beck Depression Inventory and the Self‐Rating Anxiety Scale.

Results:

The parents of daughters with an ED evidenced significantly worse dyadic adjustment than did the normal controls. When controlling for anxiety and depression, the dyadic satisfaction was lower in the mothers of daughters with ANR and BN, when compared to controls without pathology. The dyadic cohesion was lower in mothers of daughters with ANB, and the total adjustment was lower in the mothers of the ANB and BN groups versus CN group.

Conclusion:

These findings do not permit the attribution of the ED to the parents, because the poor dyadic adjustment could be an effect of the family burden. However, these findings suggest that treatment on ED should be supplemented by interventions aimed at the parents' dyadic adjustment. Copyright © 2003 John Wiley & Sons, Ltd and Eating Disorders Association.
Cognitive and behavioural characteristics are associated with personality dimensions in patients with eating disorders
Authors: Vervaet M. , Audenaert K. , van Heeringen C.
Published: September 2003

DSM‐IV categorizes eating disorders according to behavioural and cognitive characteristics. Based on personality‐related and biological research, hypotheses have been formulated to explain differences in the symptomatology between the various types of eating disorders. Therefore, the study of the association between personality‐related characteristics and behavioural and cognitive characteristics may contribute to our understanding of the causes and course of eating disorders. This study aimed, first, at describing personality characteristics (using Cloninger's Temperament and Character Inventory) in a group of eating disordered patients (n = 272) according to the type of eating disorder. Three groups were compared: restricting anorexics (n = 71), purging anorexics (n = 84) and bulimics (n = 118). Secondly, the association between personality characteristics and cognitive and behavioural aspects, using the Eating Disorders Inventory and the Dutch Eating Behaviour Questionnaire, was measured. In bulimics, positive correlations were found between novelty seeking on the one hand and external and emotional eating and bulimia on the other. Contrary to expectation, there was no significant correlation between novelty seeking and body dissatisfaction in bulimics. The significant difference between the restricting and purging type of anorexics regarding self‐directedness, and restrained and emotional eating and drive for thinness corresponded with the significant negative correlation between these characteristics. Copyright © 2003 John Wiley & Sons, Ltd and Eating Disorders Association.
Short‐term follow‐up of severe bulimia nervosa after inpatient treatment
Authors: Rø Øyvind , Martinsen Egil W. , Hoffart Asle , Rosenvinge Jan H.
Published: September 2003

Objective:

There are few follow‐up studies on outcome for treatment‐resistant bulimics with comorbid personality disorders. Inpatient treatment may be one option for patients who have not responded to outpatient therapy. The aim of this prospective study was to report on the 1‐year follow‐up of long‐term severe bulimic patients treated in an inpatient eating disorder unit.

Method:

Fifty‐four patients were treated in a 4‐month specialized group treatment programme for bulimia nervosa. Patients were assessed using the Eating Disorder Examination interview (EDE), the Eating Disorder Inventory (EDI) and the Symptom Check List (SCL‐90‐R) at pre‐treatment, post‐treatment and at 1 year after the start of treatment. Fifty patients with a mean age of 31 years were available for the follow‐up assessment. On admission 72 per cent of the patients had bulimia nervosa, 26 per cent had unspecified eating disorder (EDNOS) and 2 per cent had the bulimic subtype of anorexia nervosa.

Results:

Twenty‐two (44 per cent) patients had good outcome at follow‐up (i.e. reduction of binges and/or purging by more than 75 per cent). Fourteen (28 per cent) had intermediate outcome (i.e. 25–74 per cent reduction of binges and/or purging) and 14 (28 per cent) had poor outcome (i.e. less than 25 per cent reduction in binging and/or purging or a symptom increase). There were significant reductions in most EDE, EDI and SCL‐90‐R subscale scores from pre‐treatment to follow‐up. The improvement on all of these subscales occurred during inpatient treatment and there were no significant changes from post‐treatment to follow‐up.

Conclusion:

Bulimic symptoms and general psychiatric symptoms were substantially reduced during the 4‐month inpatient treatment and these improvements were sustained at the follow‐up. Inpatient treatment may thus be an option for treatment‐resistant bulimia nervosa. Copyright © 2003 John Wiley & Sons, Ltd and Eating Disorders Association.
Lysophosphatidic acid regulates the proliferation and migration of olfactory ensheathing cells in vitro
Authors: Yan Henglin , Lu Dongchen , Rivkees Scott A.
Published: September 2003

Olfactory ensheathing cells (OECs) are a unique type of macroglia with axonal growth‐promoting properties. However, our understanding of the factors that regulate OECs is at early stages. Lysophosphatidic acid (LPA) is a lipid that influences diverse functions in the nervous system. Recent studies suggest that glial cells, including astrocytes and Schwann cells, are important targets of LPA. However, the influences of LPA on OECs are not known. To address if LPA can influence OECs, we examined effects of LPA on the proliferation and migration of OECs and intracellular effector events. Initially, we observed that OECs expressed the genes for LPA1, LPA2, and LPA3 receptors. When OECs were treated with LPA, we observed stimulated proliferation and migration of OECs. Treatment of OECs with LPA also induced actin cytoskeleton reorganization and focal adhesion assembly. These effects of LPA were blocked by treatment with C3 exoenzyme or Y‐27632, which inhibit Rho‐GTPase and Rho‐associated kinase, respectively. Effects of LPA on OEC proliferation were blocked by the MEK inhibitors PD098059 and U0126 and by the phosphotidylinositol 3‐kinase (PI 3‐K) inhibitors LY0294002 and wortmannin. These results show that LPA acts via Rho‐GTPase, MAPK, and PI 3‐K signaling cascades to influence OEC proliferation, migration, and cytoskeleton assembly. © 2003 Wiley‐Liss, Inc.
Regulation of tissue inhibitor of metalloproteinase‐1 by astrocytes: Links to HIV‐1 dementia
Authors: Suryadevara Radhika , Holter Spring , Borgmann Kathleen , Persidsky Raisa , Labenz‐Zink Christine , Persidsky Yuri , Gendelman Howard E. , Wu Li , Ghorpade Anuja
Published: September 2003

The neuropathogenesis of HIV‐1‐associated dementia (HAD) revolves around the secretion of toxic molecules from infected and immune‐competent mononuclear phagocytes. Astrocyte activation occurs in parallel but limited insights are available for its role in neurotoxicity and cognitive dysfunction. One means in which astrocytes may affect disease is through their production of tissue inhibitors of metalloproteinases (TIMPs). TIMPs are regulators of matrix metalloproteinases, enzymes that affect blood‐brain barrier integrity through altering the extracellular matrix. We hypothesized that in response to injury and inflammation in HAD, astrocytes regulate the production of TIMP‐1, the inducible type of TIMP that is important in inflammation. To address astrocyte‐mediated TIMP‐1 regulation in HAD, we evaluated the responses of primary human to IL‐1β and HIV‐1. TIMP‐1 levels in plasma, CSF, and brain tissue of control, HIV‐1 infected patients without cognitive impairment, and HAD patients were also studied. Our data show that an upregulation of TIMP‐1 results from astrocytes acutely activated with IL‐1β. In contrast, CSF and brain tissue samples from HAD patients showed reduced TIMP‐1 levels compared to seronegative controls. MMP‐2 levels in brains showed the opposite. Consistent with this, prolonged activation of astrocytes led to a reduction in TIMP‐1 and MMP‐2, but a sustained elevation in MMP‐1. Our data suggest that in diseased brain tissue, the ability of astrocytes to counteract the destructive effects of MMP through expression of TIMP‐1 is diminished by chronic activation. Our studies reveal new opportunities for repair‐based therapeutic strategies in HAD. © 2003 Wiley‐Liss, Inc.
Microtubules are critical for radial glial morphology: Possible regulation by MAPs and MARKs
Authors: Li Hedong , Berlin Yana , Hart Ronald P. , Grumet Martin
Published: September 2003

Radial glia are a polarized cell type that in most neural regions appear only transiently during development. They have long been recognized as glia or glial progenitors that support neuronal migration. Recent evidence indicates that radial glia also give rise to neurons and appear to be a major population of dividing precursor cells in the embryonic cortical ventricular zone. Radial glia extend long processes from the ventricular zone to the pial surface that provide guides for neuronal migration. We reasoned that the unique morphology of radial glia is due to the composition and organization of their cytoskeleton. In this present study, we have used C6‐R, a radial glial‐like cell line and isolated perinatal cerebellar radial glia to ask what are the critical cytoskeletal elements in radial glial cells and how they are regulated. Treatments with nocodazole and cytochalasin D showed that microtubules, but not microfilaments, are critical for the polarized morphology of radial glia. In addition, quantitative real‐time PCR indicated that certain mRNAs specific for microtubule‐associated proteins (MAPs) are selectively expressed in radial glia. These results together with the known ability of microtubule affinity‐regulating kinases to regulate microtubule organization suggest that microtubules and MAPs are critical for the morphology of radial glia. © 2003 Wiley‐Liss, Inc.
Neuronal glutamate transporter EAAT4 is expressed in astrocytes
Authors: Hu Wen‐Hui , Walters Winston M. , Xia Xiao‐Mei , Karmally Shaffiat A. , Bethea John R.
Published: September 2003

High‐affinity excitatory amino acid transporters (EAATs) are essential to terminate glutamatergic neurotransmission and to prevent excitotoxicity. To date, five distinct EAATs have been cloned from animal and human tissues: GLAST (EAAT1), GLT‐1 (EAAT2), EAAC1 (EAAT3), EAAT4, and EAAT5. EAAT1 and EAAT2 are commonly known as glial glutamate transporters, whereas EAAT3, EAAT4, and EAAT5 are neuronal. EAAT4 is largely expressed in cerebellar Purkinje cells. In this study, using immunohistochemistry and Western blotting, we found that EAAT4‐like immunoreactivity (ir) is enriched in the spinal cord and forebrain. Double‐labeled fluorescent immunostaining and confocal image analysis indicated that EAAT4‐like ir colocalizes with an astrocytic marker, glial fibrillary acidic protein (GFAP). The astrocytic localization of EAAT4 was further confirmed in astrocyte cultures by double‐labeled fluorescent immunocytochemistry and Western blotting. Reverse transcriptase‐polymerase chain reaction analysis demonstrated mRNA expression of EAAT4 in astrocyte cultures. Sequencing confirmed the specificity of the amplified fragment. These results demonstrate that EAAT4 is expressed in astrocytes. This astrocytic localization of neuronal EAAT4 may reveal a new function of EAAT4 in the central nervous system. © 2003 Wiley‐Liss, Inc.
Molecular cloning, tissue expression, and partial characterization of the major fish CNS myelin protein 36k
Authors: Moll Wolfgang , Lanwert Carsten , Jeserich Gunnar
Published: September 2003

A full‐length cDNA clone encoding the major structural protein of trout CNS myelin 36K was isolated and sequenced. The deduced amino acid sequence did not reveal a putative transmembrane domain and exhibited no structural homology with any of the known myelin proteins. 36K instead shared characteristic structural elements with enzymes of the short‐chain dehydrogenase family. The highest similarity in the database (60%), however, was obtained with a human protein of unknown function. By Northern blotting, a single mRNA species of about 2 kb was identified, which was expressed in brain tissue but not in liver. By in situ hybridization, a selective labeling of myelinating glial cells in the trout CNS but not in the PNS was revealed. The developmental appearance of the 36K transcript closely coincided with a period of active myelin deposition in most regions of the trout brain. As a first step in elucidating the structural and biochemical role of 36K for myelin formation and maintenance, we have overexpressed it in Escherichia coli as a soluble His‐tag fusion protein and purified it in high yield by Ni+‐chelated affinity chromatography. By SDS‐PAGE, a single band of the expected molecular size was revealed, which heavily cross‐reacted with polyclonal antibodies generated against the native protein. The results of circular dichroism spectroscopy are compatible with a βαβ‐barrel structure (Rossman fold), confirming the results of computer‐assisted secondary structure predictions. © 2003 Wiley‐Liss, Inc.
Endothelin‐1 increases 2‐arachidonoyl glycerol (2‐AG) production in astrocytes
Authors: Walter Lisa , Stella Nephi
Published: September 2003

Astrocytes play an important role in neuroprotective responses. Recent studies indicate that endothelin‐1, a neuropeptide upregulated during brain injury, increases levels of the endocannabinoid anandamide, a lipid with neuroprotective properties, in astrocytes in primary cultures. However, whether this neuropeptide also alters levels of 2‐arachidonoyl glycerol (2‐AG), the most abundant endocannabinoid in the CNS, in astrocytes remains unknown. In addition, 2‐AG levels in astrocytes have never been measured. In this report we use chemical ionization gas chromatography/mass spectrometry to quantify picomole amounts of 2‐AG in primary cultures of mouse astrocytes. We also demonstrate that endothelin‐1 increases 2‐AG production by 5‐fold in these cells, a response that requires extracellular calcium and endothelin‐1(A) receptor engagement. Immunocytochemistry showed that although cultured mouse neurons and microglia express cannabinoid receptors, cultured astrocytes do not. The data suggest that endothelin‐1 modulates 2‐AG production in astrocytes and that this endocannabinoid may participate in paracrine signaling toward neurons and microglia. © 2003 Wiley‐Liss, Inc.
Astrocytic ceruloplasmin expression, which is induced by IL‐1β and by traumatic brain injury, increases in the absence of the IL‐1 type 1 receptor
Authors: Kuhlow Christopher J. , Krady J. Kyle , Basu Anirban , Levison Steven W.
Published: September 2003

IL‐1α and IL‐1β are induced immediately after insults to the brain, and signaling through the type 1 IL‐1 receptor is essential for a normal microglial and astroglial response to injury. To better understand which genes are induced in astrocytes by IL‐1β, we used the unbiased technique of differential display to analyze mouse astroglial gene expression after IL‐1β treatment. Two novel genes were induced, as well as the gene for ceruloplasmin, a ferroxidase with antioxidant properties. Ceruloplasmin was analyzed further by Northern and Western blot. RNA and protein levels of ceruloplasmin were increased when astrocytes were treated with IL‐1β. To determine whether the IL‐1 type 1 receptor (IL‐1R1) is essential for the injury‐induced expression of ceruloplasmin, a Western blot analysis was performed after a traumatic brain injury on mice that were IL‐1R1‐deficient. Ceruloplasmin increased significantly above controls after injury; however, injury‐induced levels of ceruloplasmin were lower in IL‐1R1‐deficient (2.7‐fold increase) than in the wild‐type animals (3.5‐fold increase). These data indicate that while IL‐1R1 deletion has a slight effect on ceruloplasmin expression, it is not essential for either the basal or the induced expression of ceruloplasmin in vivo. Since ceruloplasmin buffers free copper, oxidizes ferrous iron, and catalyzes the dismutation of free radicals, increased levels of ceruloplasmin likely protect neurons and glia from sustaining damage after injury. Furthermore, as the IL‐1R1 has been proposed to be a target for achieving neuroprotection after injury, these data suggest that the protection afforded by ceruloplasmin will be retained even when the IL‐1R1 is antagonized. © 2003 Wiley‐Liss, Inc.
erbB3 is dispensable for oligodendrocyte development in vitro and in vivo
Authors: Schmucker Johannes , Ader Marius , Brockschnieder Damian , Brodarac Andreja , Bartsch Udo , Riethmacher Dieter
Published: September 2003

During development and in the adult, erbB2, erbB3, and erbB4 are expressed in many tissues and as heterodimers (B2/B3, B2/B4) serve as receptors for neuregulins. The general importance of neuregulin receptors for development is underlined by the observed embryonic (erbB2, erbB4) or perinatal (erbB3) lethality in mouse mutants. These mutants further revealed the fundamental role of the erbB2/erbB3 heterodimer for proper Schwann cell development, the ensheathing glia of the peripheral nervous system. However, only little is known about the functions of neuregulins and their receptors during postnatal development and in the adult. erbB2 and erbB3 during late embryogenesis and postnatally are expressed in different areas and cell types of the central nervous system, including oligodendrocytes, the ensheathing glia of the central nervous system. As terminal differentiation of oligodendrocytes peaks during postnatal development, it is not possible to use the neuregulin receptor mouse mutants to study terminal differentiation of oligodendrocytes in their absence in vivo. In order to investigate possible functions of the erbB3 gene in oligodendrocytes, we employed two different techniques. First, we directed the differentiation of erbB3‐deficient embryonic stem cells into neural cell types to analyze the development of oligodendrocytes in the absence of erbB3 in vitro. Second, we grafted neural stem cells from spinal cords of erbB3 mutants into the retina of young mice to monitor oligodendrocyte differentiation and myelination in vivo. Results of both experimental approaches clearly show that erbB3 is not required for normal oligodendrocyte development and myelination. © 2003 Wiley‐Liss, Inc.
Chronic glial activation, neurodegeneration, and APP immunoreactive deposits following acute administration of double‐stranded RNA
Authors: Melton Lisa M. , Keith Alexander B. , Davis Sue , Oakley Arthur E. , Edwardson James A. , Morris Christopher M.
Published: September 2003

Several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, are associated with immunocompetent microglia, leading to the suggestion that chronic glial‐mediated inflammation contributes to the neurodegeneration seen in these diseases. Little direct evidence supports this hypothesis, and no suitable rodent models exist that do not involve the use of blunt trauma or ischaemia, events that are infrequently encountered in the human disease state. In the present study, we report that administration of double‐stranded RNA, a classical inducer of interferon‐γ (IFN‐γ), causes rapid and persistent activation of microglia and astrocytes, as well as induction of interleukin‐1β (IL‐β) and nitric oxide synthase. In close temporal succession to glial activation, there is neurodegeneration, with neuron loss involving apoptosis in selected brain regions including the septal nucleus, hippocampus, cortex and thalamus, along with hippocampal atrophy. This neuronal loss is accompanied by punctate deposits of material that are immunoreactive for amyloid precursor protein, β‐amyloid peptide (Aβ), and apolipoprotein E. The findings may have clinical relevance, since the administration of the nonsteroidal antiinflammatory agent (NSAID) ibuprofen markedly reduces the neurodegeneration observed in the absence of significant glial inhibition. These findings may be relevant to the pathogenesis of Alzheimer's disease in particular, and to other neurodegenerative diseases involving inflammation. © 2003 Wiley‐Liss, Inc.
Dissociation of human and computer voices in the brain: Evidence for a preattentive gestalt‐like perception
Authors: Lattner Sonja , Maess Burkhard , Wang Yunhua , Schauer Michael , Alter Kai , Friederici Angela D.
Published: September 2003

We investigated the early (“preattentive”) cortical processing of voice information, using the so‐called “mismatch response.” This brain potential allows inferences to be made about the sensory short‐term store. Most importantly, the mismatch potential also provides information about the organization of long‐term memory traces in the auditory system. Such traces have reliably been reported for phonemes. However, it is unclear whether they also exist for human voice information. To explore this issue, 10 healthy subjects were presented with a single word stimulus uttered by voices of different prototypicality (natural, manipulated, synthetic) in a mismatch experiment (stimulus duration 380 msec, onset‐to‐onset interval 900 msec). The event‐related magnetic fields were recorded by a 148‐channel whole‐head magnetometer and a source current density modeling of the magnetic field data was performed using a minimum‐norm estimate. Each deviating voice signal in a series of standard‐voice stimuli evoked a mismatch response that was localized in temporal brain regions bilaterally. Increased mismatch related magnetic flux was observed in response to decreased prototypicality of a presented voice signal, but did not correspond to the acoustic similarity of standard voice and deviant voices. We, therefore, conclude that the mismatch activation predominantly reflects the ecological validity of the voice signals. We further demonstrate that the findings cannot be explained by mere acoustic feature processing, but rather point towards a holistic mapping of the incoming voice signal onto long‐term representations in the auditory memory. Hum. Brain Mapping 20:13–21, 2003. © 2003 Wiley‐Liss, Inc.
Brain activations during conscious self‐monitoring of speech production with delayed auditory feedback: An fMRI study
Authors: Hashimoto Yasuki , Sakai Kuniyoshi L.
Published: September 2003

When a speaker's voice returns to one's own ears with a 200‐ms delay, the delay causes the speaker to speak less fluently. This phenomenon is called a delayed auditory feedback (DAF) effect. To investigate neural mechanisms of speech processing through the DAF effect, we conducted a functional magnetic resonance imaging (fMRI) experiment, in which we designed a paradigm to explore the conscious overt‐speech processing and the automatic overt‐speech processing separately, while reducing articulatory motion artifacts. The subjects were instructed to (1) read aloud visually presented sentences under real‐time auditory feedback (NORMAL), (2) read aloud rapidly under real‐time auditory feedback (FAST), (3) read aloud slowly under real‐time auditory feedback (SLOW), and (4) read aloud under DAF (DELAY). In the contrasts of DELAY‐NORMAL, DELAY‐FAST, and DELAY‐SLOW, the bilateral superior temporal gyrus (STG), the supramarginal gyrus (SMG), and the middle temporal gyrus (MTG) showed significant activation. Moreover, we found that the STG activation was correlated with the degree of DAF effect for all subjects. Because the temporo‐parietal regions did not show significant activation in the comparisons among NORMAL, FAST, and SLOW conditions, we can exclude the possibility that its activation is due to speech rates or enhanced attention to altered speech sounds. These results suggest that the temporo‐parietal regions function as a conscious self‐monitoring system to support an automatic speech production system. Hum. Brain Mapping 20:22–28, 2003. © 2003 Wiley‐Liss, Inc.
Stimulus repetition and hemodynamic response refractoriness in event‐related fMRI
Authors: Soon Chun‐Siong , Venkatraman Vinod , Chee Michael W.L.
Published: September 2003

We investigated the extent of hemodynamic recovery following the paired presentation of either identical or different faces at two different inter‐stimulus intervals (ISI). Signal recovery was consistently better at an ISI of 6 sec compared to 3 sec. Significantly less signal recovery was associated with identical faces compared to different faces in bilateral mid‐fusiform and right prefrontal regions but not in the calcarine and posterior fusiform regions. Repetition suppression effects contributed significantly to incomplete signal recovery in a region‐specific manner. Simulations using empirically derived data suggest that experiments with shorter ISI (average 4.5–6.0 sec) are as sensitive as experiments with intermediate ISI (average 9 sec) in detecting response differences if experimental duration is equivalent. However, designs using intermediate ISI may be more appropriate if the expected difference in responses is small and if the number of suitable stimuli is limited. Hum. Brain Mapping 20:1–12, 2003. © 2003 Wiley‐Liss, Inc.
Directly mapping magnetic field effects of neuronal activity by magnetic resonance imaging
Authors: Xiong Jinhu , Fox Peter T. , Gao Jia‐Hong
Published: September 2003

Magnetic resonance imaging (MRI) of brain functional activity relies principally on changes in cerebral hemodynamics, which are more spatially and temporally distributed than the underlying neuronal activity changes. We present a novel MRI technique for mapping brain functional activity by directly detecting magnetic fields induced by neuronal firing. Using a well‐established visuomotor paradigm, the locations and latencies of activations in visual, motor, and premotor cortices were imaged at a temporal resolution of 100 msec and a spatial resolution of 3 mm, and were found to be in consistent with the electrophysiological and functional MRI (fMRI) literature. Signal strength was comparable to traditional event‐related fMRI methods: about 1% of the baseline signal. The magnetic‐source MRI technique greatly increases the temporal accuracy in detecting neuronal activity, providing a powerful new tool for mapping brain functional organization in human and animals. Hum. Brain Mapping 20:41–49, 2003. © 2003 Wiley‐Liss, Inc.
Functional magnetic resonance imaging of verbal fluency and confrontation naming using compressed image acquisition to permit overt responses
Authors: Abrahams Sharon , Goldstein Laura H. , Simmons Andy , Brammer Michael J. , Williams Steve C.R. , Giampietro Vincent P. , Andrew Chris M. , Leigh P. Nigel
Published: September 2003

Verbal fluency and confrontation naming, two tests of word retrieval, are of great utility in the field of cognitive neuroscience. However, in the context of functional magnetic resonance imaging (fMRI), movement artefact has necessitated the use of covert paradigms, which has limited clinical application. We developed two overt fMRI paradigms that allowed for performance measurement and hence were appropriate for use with patient groups. The paradigms incorporated a blocked‐design and compressed‐acquisition methodology where cues were presented and responses made in a “silent” period allowing for performance measurement. The slow response pace was specifically designed for older and potentially cognitively impaired participants. Verbal fluency was associated with activation in the middle frontal gyrus (Brodmann areas 46 and 9), anterior cingulate gyrus and inferior frontal gyrus (area 44 and 45). Confrontation naming activated areas of the temporo‐occipital cortices (areas 18, 19, and 37) and the inferior frontal gyrus. The two paradigms successfully activated regions involved in executive and word retrieval processes and overcame the potential artefacts resulting from overt speech during image acquisition, providing useful neuropsychological tools to investigate cognitive deficits in clinical populations. Hum. Brain Mapping 20:29–40, 2003. © 2003 Wiley‐Liss, Inc.
Betulinic acid: A new cytotoxic compound against malignant head and neck cancer cells
Authors: Thurnher Dietmar , Turhani Dritan , Pelzmann Martina , Wannemacher Bettina , Knerer Birgit , Formanek Michael , Wacheck Volker , Selzer Edgar
Published: September 2003

Background.

A new compound, betulinic acid, has been found to be cytotoxic against a variety of tumor cells originating from the neural crest. Its efficacy against head and neck squamous cellular carcinoma cell lines has so far not been tested.

Methods.

Cell numbers were assayed by automated counting; caspase activation and programmed cell death were determined using an antibody specific for an apoptosis‐associated epitope in epithelial cells. The expression pattern of Bcl‐2 family members was assessed by Western blotting.

Results.

In two HNSCC cell lines betulinic acid induced apoptosis, which was characterized by a dose‐dependent reduction in cell numbers, emergence of apoptotic cells, and an increase in caspase activity. Western blot analysis of the expression of various Bcl‐2 family members in betulinic acid–treated cells showed, surprisingly, a suppression of the expression of the proapoptotic protein Bax but no changes in Mcl‐1 or Bcl‐2 expression.

Conclusion.

These data clearly demonstrate for the first time that betulinic acid has apoptotic activity against HNSCC cells. © 2003 Wiley Periodicals, Inc. Head Neck 25: 732–740, 2003
Salvage laryngectomy and pharyngocutaneous fistulae after primary radiotherapy for head and neck cancer: A national survey from DAHANCA
Authors: Grau Cai , Johansen Lars Vendelbo , Hansen Hanne Sand , Andersen Elo , Godballe Christian , Andersen Lisbeth Juhler , Hald Jesper , Møller Henrik , Overgaard Marie , Bastholt Lars , Greisen Ole , Harbo Grethe , Hansen Olfred , Overgaard Jens
Published: September 2003

Objective.

In 1998, the Danish Society for Head and Neck Oncology decided to conduct a nationwide survey at the five head and neck oncology centers with the aim of evaluating the surgical outcome of salvage laryngectomy after radiotherapy with special emphasis on identifying factors that could contribute to the development of pharyngocutaneous fistulae.

Patients.

A total of 472 consecutive patients undergoing postirradiation salvage laryngectomy in the period July 1, 1987–June 30, 1997 were recorded at the five head and neck oncology centers in Denmark. Age ranged from 36 to 84 years, median 63 years, 405 men and 67 women. Primary tumor site was glottic larynx (n = 242), supraglottic larynx (n = 149), other larynx (n = 45), pharynx (n = 27), and other (n = 9). All patients had received prior radiotherapy.

Results.

Median time between radiotherapy and laryngectomy was 10 months (range, 1–348 months). A total of 89 fistulae lasting at least 2 weeks were observed, corresponding to an overall average fistulae risk of 19%. The number of performed laryngectomies per year decreased linearly (from 58 to 37), whereas the annual number of fistulae increased slightly (from 7 to 11), which meant that the corresponding estimated fistulae risk increased significantly from 12% in 1987 to 30% in 1997. Other significant risk factors for fistulae in univariate analysis included younger patient age, primary advanced T and N stage, nonglottic primary site, resection of hyoid bone, high total radiation dose, and large radiation fields. Multiple logistic regression analysis of these parameters suggested that nonglottic tumor site, late laryngectomy period (1987–1992 vs 1993–1997), and advanced initial T stage were independent prognostic factors for fistulae risk. Surgical parameters like resection of thyroid/tongue base/trachea or radiotherapy parameters like overall treatment time or fractions per week did not influence fistulae risk.

Conclusions.

The risk of fistulae is especially high in patients initially treated with radiotherapy for nonglottic advanced stage tumors. A significant decrease in the number of performed salvage laryngectomies over the 10 years was seen. Over the same time period, the annual number of fistulae remained almost constant. The resulting more than doubling of fistulae rate could thus in part be explained by less surgical routine. © 2003 Wiley Periodicals, Inc. Head Neck 25: 711–716, 2003
Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: A multicenter, randomized, double‐blind, phase III study in North America
Authors: Castro Dan J. , Sridhar Kasi S. , Garewal Harinder S. , Mills Glenn M. , Wenig Barry L , Dunphy Frank R. , Costantino Peter D. , Leavitt Richard D. , Stewart Morgan E. , Orenberg Elaine K.
Published: September 2003

Background.

The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor‐related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Patients and Methods.

Eighty‐seven patients were randomly assigned to either CDDP/epi or placebo gel in this phase III, double‐blind study. Tumors were ≤20 cm3; most recurrences (88%) were in a previously irradiated field. The most symptomatic or threatening tumor was designated as the target tumor. Dose: 0.25 mL CDDP/epi gel/cm3 tumor volume. Treatments: ≤6 weekly intratumoral injections in an 8‐week period. Primary outcomes: target tumor response and symptom relief.

Results.

During the blinded phase, 34% (21 of 62) of patients achieved an objective response (CR or PR) in the target tumor treated with CDDP/epi gel vs 0% (0 of 24) treated with placebo gel (p < .001). Responses occurred within a median of four treatments (range, 2–6) and were durable (median, 95 days; range, 34–168+ days). More patients treated with CDDP/epi gel achieved palliative benefit than did those treated with placebo gel (37% vs 12%, p = .036). Most frequent side effects were local pain and local cutaneous reactions, which resolved over 3–12 weeks. Renal and hematologic toxicities were rare.

Conclusions.

This phase III trial showed that CDDP/epi gel significantly reduces tumor burden, palliates tumor‐related symptoms, and is an effective local treatment for recurrent tumors. © 2003 Wiley Periodicals, Inc. Head Neck 25: 717–731, 2003
Does feeding tube placement predict for long‐term swallowing disability after radiotherapy for head and neck cancer?
Authors: Al‐Othman Majid O. F. , Amdur Robert J. , Morris Christopher G. , Hinerman Russell W. , Mendenhall William M.
Published: September 2003

Purpose.

To evaluate feeding tube use.

Materials and Methods.

Nine hundred thirty‐four patients were treated with radiotherapy (RT).

Results.

Feeding tubes were placed in 235 patients (25%): 212 patients (22.5%) for acute toxicity, 18 patients (2%) for late effects, and 5 patients (0.5%) for both. Median duration of tube dependence for acute toxicity was 3.8 months. Multivariate analysis revealed that feeding tube placement for acute toxicity was increased with higher RT dose (p < .0001), adjuvant chemotherapy (p = .0002), advanced age (p = .0002), and the presence of neck disease (p = .0045). The risk of a feeding tube for late effects was 2% at 5 years. The likelihood of feeding tube placement for late effects was greater for women (p = .0293), higher RT dose (p = .0345), and primary sites, including the hypopharynx and multiple synchronous primary tumors (p = .0360). Feeding tube placement for late effects was unrelated to tube placement for acute toxicity.

Conclusion.

Likelihood of long‐term feeding tube dependence was low and unrelated to placement for acute effects. © 2003 Wiley Periodicals, Inc. Head Neck 25: 741–747, 2003
Reduction of occult metastatic disease by extension of the supraomohyoid neck dissection to include level IV
Authors: Crean St‐John , Hoffman A. , Potts John , Fardy M.J.
Published: September 2003

Background.

Patients with clinically N0 necks will undergo elective removal of lymphatic tissue from levels I, II, and III as part of their routine surgical management. Level IV is omitted on the basis that there is negligible chance of containing significant occult disease. Evidence to support this approach is minimal, and the aim of this study was to increase the yield of metastatically involved lymph nodes by simply extending the supraomohyoid neck dissection (SOHND) to include level IV.

Methods.

The records of 49 patients with cancer of the oral cavity undergoing extended supraomohyoid neck dissection (ESOHND) during the period January 1996–March 1999 were reviewed. All patients were staged as having N0 disease. The follow‐up period ranged from 12 to 36 months.

Results.

Thirteen of 55 N0 stage necks showed occult metastasis (26.5%). Neck failure rate occurred in 4 of 49 patients (8.2%). Neck failure rate in the pN0 group was 5.4% and in the pN+ group was 16.6%. Complication rates of ESOHND were noted as 3.6%. No long‐term morbidity arose. Occult metastasis in level IV occurred in 5 of 49 cases (10%). Two cases involved other surgical levels.

Conclusions.

ESOHND as performed in this study removed occult level IV metastatic regional disease from an extra 10% of patients that, if the patients had undergone SOHND, would have remained undiscovered. No long‐term morbidity is associated with this procedure that the authors now recommend as a first‐line treatment in all patients with N0 necks. © 2003 Wiley Periodicals, Inc. Head Neck 25: 758–762, 2003
Kimura's disease of parotid gland presenting as solitary parotid swelling
Authors: Arshad A. R.
Published: September 2003

Background.

Kimura's disease is a chronic inflammatory disorder of unknown etiology commonly seen among orientals and characterized histologically by lymphatic follicles, vascular proliferation, and marked eosinophilic infiltration. It has a predilection for the head and neck region. The lesion is benign but can be mistaken to be a malignant lesion.

Methods.

Between January 1987 and December 1999, eight cases of Kimura's disease were treated at the Department of Plastic Surgery, Hospital Kuala Lumpur. All the patients underwent surgical excision followed by initial high‐dose steroid therapy and low‐dose maintenance.

Results.

All the patients are men, seven belong to the Malay race and one is Chinese. The patients' ages at diagnosis are 18 to 46 years. All were initially seen with swelling in the parotid gland, ranging from 1 year to 20 years' duration. Pruritus of the overlying skin was seen in seven patients. Treatment by surgical excision and steroid therapy has led to no recurrences.

Conclusion.

Kimura's disease of parotid gland is rare. It is a chronic inflammatory condition also called eosinophilic hyperplastic lymphogranuloma. Treatment by surgical excision and steroid therapy has led to no recurrences. © 2003 Wiley Periodicals, Inc. Head Neck 25: 754–757, 2003
Mandibulotomy and implant insertion
Authors: Schoen Pieter J. , Raghoebar Gerry M. , Vissink Arjan , Roodenburg Jan L. N.
Published: September 2003

Background.

A mandibulotomy can be necessary to approach a tumor in the oral cavity or oropharynx. The aim of this study was to develop and prospectively evaluate a technique enabling simultaneous performance of a mandibulotomy and insertion of endosseous implants in the same area.

Methods.

In five edentulous patients such a procedure was performed. The pilot drilling of the implants was done before performing the mandibulotomy. After tumor resection, reconstruction, and restoration of the continuity of the mandible, the final drilling and insertion of the implants were completed. In total, 20 implants were inserted. All patients received radiation therapy within 6 weeks after surgery. Implant‐supported overdentures were fabricated 6 months after irradiation. At regular time intervals, a standardized clinical and radiographic evaluation was performed.

Results.

No complications with respect to the combination of implant insertion and mandibulotomy were observed either during or after surgery. In addition, no adverse mucosal reactions were observed during the course of radiotherapy, no cases of osteoradionecrosis developed, and no implants were lost. Clinical and radiographic evaluation revealed healthy peri‐implant parameters.

Conclusion.

From this study it is concluded that, when following the technique described, a mandibulotomy can be combined safely with the insertion of implants in the ventral part of the edentulous mandible. © 2003 Wiley Periodicals, Inc. Head Neck 25: 748–753, 2003
Sinonasal adenocarcinoma: Immunohistochemical marking and expression of oncoproteins
Authors: Bashir Amani A. , Robinson Robert A. , Benda Jo A. , Smith Russell B.
Published: September 2003

Background.

Relatively little is known concerning the immunohistochemical marking of sinonasal adenocarcinoma (SNA). The most clinically problematic tumors are those that seem histologically identical to colonic adenocarcinoma, a neoplasm that may metastasize to the sinonasal region. To determine whether differentiated immunohistochemical expression of keratins could differentiate primary from metastatic tumors and to understand the biology of these tumors, differentiated keratin and oncoprotein expression was investigated.

Methods.

Eleven patients with sinonasal adenocarcinoma were investigated for expression of cytokeratins 7 and 20 (CK7, CK20), AE 1/3, CAM 5.2, smooth muscle–specific actin, muscle‐specific actin, desmin, S‐100, carcinoembryonic antigen (CEA), p53, and HER‐2/neu.

Results.

All sinonasal adenocarcinomas of intestinal type were cytokeratin 7 positive. None of the tumors showed myoepithelial differentiation. Strong HER‐2/neu staining was seen in some tumors.

Conclusions.

Strong HER‐2/neu staining in some cases suggests this oncogene may be involved in the genesis of SNA. Immunohistochemical staining with cytokeratin 7 may be potentially useful in differentiating primary from metastatic disease in sinonasal adenocarcinomas of the intestinal subtype. © 2003 Wiley Periodicals, Inc. Head Neck 25: 763–771, 2003